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Sample records for common cellular events

  1. The Mosaic Theory Revisited: Common Molecular Mechanisms Coordinating Diverse Organ and Cellular Events in Hypertension

    PubMed Central

    Harrison, David G.

    2012-01-01

    Over 60 years ago, Dr. Irvine Page proposed the Mosaic Theory of hypertension, which states that many factors, including genetics, environment, adaptive, neural, mechanical and hormonal perturbations interdigitate to raise blood pressure. In the past two decades, it has become clear that common molecular and cellular events in various organs underlie many features of the Mosaic Theory. Two of these are the production of reactive oxygen species (ROS) and inflammation. These factors increase neuronal firing in specific brain centers, increase sympathetic outflow, alter vascular tone and morphology and promote sodium retention in the kidney. Moreover, factors such as genetics and environment contribute to oxidant generation and inflammation. Other common cellular signals, including calcium signaling and endoplasmic reticulum stress are similarly perturbed in different cells in hypertension and contribute to components of Dr. Page’s theory. Thus, Dr. Page’s Mosaic Theory formed a framework for future studies of molecular and cellular signals in the context of hypertension, and has greatly aided our understanding of this complex disease. PMID:23321405

  2. Cellular events and biomarkers of wound healing

    PubMed Central

    Shah, Jumaat Mohd. Yussof; Omar, Effat; Pai, Dinker R.; Sood, Suneet

    2012-01-01

    Researchers have identified several of the cellular events associated with wound healing. Platelets, neutrophils, macrophages, and fibroblasts primarily contribute to the process. They release cytokines including interleukins (ILs) and TNF-α, and growth factors, of which platelet-derived growth factor (PDGF) is perhaps the most important. The cytokines and growth factors manipulate the inflammatory phase of healing. Cytokines are chemotactic for white cells and fibroblasts, while the growth factors initiate fibroblast and keratinocyte proliferation. Inflammation is followed by the proliferation of fibroblasts, which lay down the extracellular matrix. Simultaneously, various white cells and other connective tissue cells release both the matrix metalloproteinases (MMPs) and the tissue inhibitors of these metalloproteinases (TIMPs). MMPs remove damaged structural proteins such as collagen, while the fibroblasts lay down fresh extracellular matrix proteins. Fluid collected from acute, healing wounds contains growth factors, and stimulates fibroblast proliferation, but fluid collected from chronic, nonhealing wounds does not. Fibroblasts from chronic wounds do not respond to chronic wound fluid, probably because the fibroblasts of these wounds have lost the receptors that respond to cytokines and growth factors. Nonhealing wounds contain high levels of IL1, IL6, and MMPs, and an abnormally high MMP/TIMP ratio. Clinical examination of wounds inconsistently predicts which wounds will heal when procedures like secondary closure are planned. Surgeons therefore hope that these chemicals can be used as biomarkers of wounds which have impaired ability to heal. There is also evidence that the application of growth factors like PDGF will help the healing of chronic, nonhealing wounds. PMID:23162220

  3. Cellular Neurothekeoma: A Rare Tumor with a Common Clinical Presentation

    PubMed Central

    Boukovalas, Stefanos; Rogers, Hayley; Boroumand, Nahal

    2016-01-01

    Summary: Neurothekeomas are rare benign tumors commonly found on the head, neck, and upper extremities of women and younger individuals. They are thought to be of nerve sheath origin and usually present as painless, slow growing masses. We present a case of cellular neurothekeoma on the nasal ala of an 8-year-old girl with no previous history of trauma or piercings. Differential diagnosis, treatment options, and special considerations regarding potentially atypical characteristics are discussed.

  4. Cellular Neurothekeoma: A Rare Tumor with a Common Clinical Presentation.

    PubMed

    Boukovalas, Stefanos; Rogers, Hayley; Boroumand, Nahal; Cole, Eric Lowry

    2016-08-01

    Neurothekeomas are rare benign tumors commonly found on the head, neck, and upper extremities of women and younger individuals. They are thought to be of nerve sheath origin and usually present as painless, slow growing masses. We present a case of cellular neurothekeoma on the nasal ala of an 8-year-old girl with no previous history of trauma or piercings. Differential diagnosis, treatment options, and special considerations regarding potentially atypical characteristics are discussed. PMID:27622087

  5. Cellular Dynamic Simulator: An Event Driven Molecular Simulation Environment for Cellular Physiology

    PubMed Central

    Byrne, Michael J.; Waxham, M. Neal; Kubota, Yoshihisa

    2010-01-01

    In this paper, we present the Cellular Dynamic Simulator (CDS) for simulating diffusion and chemical reactions within crowded molecular environments. CDS is based on a novel event driven algorithm specifically designed for precise calculation of the timing of collisions, reactions and other events for each individual molecule in the environment. Generic mesh based compartments allow the creation / importation of very simple or detailed cellular structures that exist in a 3D environment. Multiple levels of compartments and static obstacles can be used to create a dense environment to mimic cellular boundaries and the intracellular space. The CDS algorithm takes into account volume exclusion and molecular crowding that may impact signaling cascades in small sub-cellular compartments such as dendritic spines. With the CDS, we can simulate simple enzyme reactions; aggregation, channel transport, as well as highly complicated chemical reaction networks of both freely diffusing and membrane bound multi-protein complexes. Components of the CDS are generally defined such that the simulator can be applied to a wide range of environments in terms of scale and level of detail. Through an initialization GUI, a simple simulation environment can be created and populated within minutes yet is powerful enough to design complex 3D cellular architecture. The initialization tool allows visual confirmation of the environment construction prior to execution by the simulator. This paper describes the CDS algorithm, design implementation, and provides an overview of the types of features available and the utility of those features are highlighted in demonstrations. PMID:20361275

  6. Using Fluctuation Analysis to Establish Causal Relations between Cellular Events without Experimental Perturbation

    PubMed Central

    Welf, Erik S.; Danuser, Gaudenz

    2014-01-01

    Experimental perturbations are commonly used to establish causal relationships between the molecular components of a pathway and their cellular functions; however, this approach suffers inherent limitations. Especially in pathways with a significant level of nonlinearity and redundancy among components, such perturbations induce compensatory responses that obscure the actual function of the targeted component in the unperturbed pathway. A complementary approach uses constitutive fluctuations in component activities to identify the hierarchy of information flow through pathways. Here, we review the motivation for using perturbation-free approaches and highlight recent advances made in using perturbation-free fluctuation analysis as a means to establish causality among cellular events. PMID:25468328

  7. Early events in annelid regeneration: a cellular perspective.

    PubMed

    Bely, Alexandra E

    2014-10-01

    The ability to regenerate extensive portions of the body is widespread among the phylum Annelida and this group includes some of the most highly regenerative animals known. Knowledge of the cellular and molecular basis of regeneration in this group is thus important for understanding how regenerative processes have evolved both within the group and across animal phyla. Here, the cellular basis of annelid regeneration is reviewed, with a focus on the earliest steps of regeneration, namely wound-healing and formation of the blastema. Information from a wide range of annelids is compiled in order to identify common and variable elements. There is a large body of valuable older literature on the cellular basis of regeneration in annelids and an effort is made to review this literature in addition to more recent studies. Annelids typically seal the wound through muscular contraction and undergo some autolysis of tissue at the site of the wound. Bodily injury elicits extensive cell migration toward the wound, involving several different types of cells. Some migrating cells form a tissue-clot and phagocytize damaged tissues, whereas others are inferred to contribute to regenerated tissue, specifically mesodermal tissue. In one annelid subgroup, the clitellates, a group of mesodermal cells, sometimes referred to as neoblasts, is inferred to migrate over considerable distances, with cells moving to the wound from several segments away. Epidermis and gut epithelia severed upon amputation typically heal by fusing with like tissue, although not always. After amputation, cellular contacts with the extracellular matrix are disrupted and major changes in cell morphology and adhesion occur within tissues near the wound. Interactions of tissues at the wound appear key for initiating a blastema, with a particularly important role suggested for the ventral nerve cord, although species are variable in this regard; longer-distance effects mediated by the brain are also reported. The

  8. Common-Cause Failure Analysis in Event Assessment

    SciTech Connect

    Dana L. Kelly; Dale M. Rasmuson

    2008-09-01

    This paper describes the approach taken by the U. S. Nuclear Regulatory Commission to the treatment of common-cause failure in probabilistic risk assessment of operational events. The approach is based upon the Basic Parameter Model for common-cause failure, and examples are illustrated using the alpha-factor parameterization, the approach adopted by the NRC in their Standardized Plant Analysis Risk (SPAR) models. The cases of a failed component (with and without shared common-cause failure potential) and a component being unavailable due to preventive maintenance or testing are addressed. The treatment of two related failure modes (e.g., failure to start and failure to run) is a new feature of this paper. These methods are being applied by the NRC in assessing the risk significance of operational events for the Significance Determination Process (SDP) and the Accident Sequence Precursor (ASP) program.

  9. Chronology of mitochondrial and cellular events during skeletal muscle ischemia-reperfusion.

    PubMed

    Paradis, Stéphanie; Charles, Anne-Laure; Meyer, Alain; Lejay, Anne; Scholey, James W; Chakfé, Nabil; Zoll, Joffrey; Geny, Bernard

    2016-06-01

    Peripheral artery disease (PAD) is a common circulatory disorder of the lower limb arteries that reduces functional capacity and quality of life of patients. Despite relatively effective available treatments, PAD is a serious public health issue associated with significant morbidity and mortality. Ischemia-reperfusion (I/R) cycles during PAD are responsible for insufficient oxygen supply, mitochondriopathy, free radical production, and inflammation and lead to events that contribute to myocyte death and remote organ failure. However, the chronology of mitochondrial and cellular events during the ischemic period and at the moment of reperfusion in skeletal muscle fibers has been poorly reviewed. Thus, after a review of the basal myocyte state and normal mitochondrial biology, we discuss the physiopathology of ischemia and reperfusion at the mitochondrial and cellular levels. First we describe the chronology of the deleterious biochemical and mitochondrial mechanisms activated by I/R. Then we discuss skeletal muscle I/R injury in the muscle environment, mitochondrial dynamics, and inflammation. A better understanding of the chronology of the events underlying I/R will allow us to identify key factors in the development of this pathology and point to suitable new therapies. Emerging data on mitochondrial dynamics should help identify new molecular and therapeutic targets and develop protective strategies against PAD. PMID:27076618

  10. LINKING MOLECULAR EVENT TO CELLULAR RESPONSES AT LOW DOSE EXPOSURES

    EPA Science Inventory

    Defining low dose radiation cancer risks is limited by our ability to measure and directly correlate relevant cellular and molecular responses occurring at low dose and dose rate with tumor formation. This deficiency has led to conservative risk assessments based on low dose ext...

  11. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    SciTech Connect

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C. ); Grzeschik, K.H. )

    1988-02-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration.

  12. Myocardial Remodeling: Cellular and Extracellular Events and Targets

    PubMed Central

    Dixon, Jennifer A.; Spinale, Francis G.

    2011-01-01

    The focus of this review is on translational studies utilizing large-animal models and clinical studies that provide fundamental insight into cellular and extracellular pathways contributing to post–myocardial infarction (MI) left ventricle (LV) remodeling. Specifically, both large-animal and clinical studies have examined the potential role of endogenous and exogenous stem cells to alter the course of LV remodeling. Interestingly, there have been alterations in LV remodeling with stem cell treatment despite a lack of long-term cell engraftment. The translation of the full potential of stem cell treatments to clinical studies has yet to be realized. The modulation of proteolytic pathways that contribute to the post-MI remodeling process has also been examined. On the basis of recent large-animal studies, there appears to be a relationship between stem cell treatment post-MI and the modification of proteolytic pathways, generating the hypothesis that stem cells leave an echo effect that moderates LV remodeling. PMID:21314431

  13. Integrated Circuit-Based Biofabrication with Common Biomaterials for Probing Cellular Biomechanics.

    PubMed

    Sung, Chun-Yen; Yang, Chung-Yao; Yeh, J Andrew; Cheng, Chao-Min

    2016-02-01

    Recent advances in bioengineering have enabled the development of biomedical tools with modifiable surface features (small-scale architecture) to mimic extracellular matrices and aid in the development of well-controlled platforms that allow for the application of mechanical stimulation for studying cellular biomechanics. An overview of recent developments in common biomaterials that can be manufactured using integrated circuit-based biofabrication is presented. Integrated circuit-based biofabrication possesses advantages including mass and diverse production capacities for fabricating in vitro biomedical devices. This review highlights the use of common biomaterials that have been most frequently used to study cellular biomechanics. In addition, the influence of various small-scale characteristics on common biomaterial surfaces for a range of different cell types is discussed. PMID:26708959

  14. Identification of the "minimal triangle" and other common event-to-event transitions in conflict and containment incidents.

    PubMed

    Bowers, Len; James, Karen; Quirk, Alan; Wright, Steve; Williams, Hilary; Stewart, Duncan

    2013-07-01

    Although individual conflict and containment events among acute psychiatric inpatients have been studied in some detail, the relationship of these events to each other has not. In particular, little is known about the temporal order of events for individual patients. This study aimed to identify the most common pathways from event to event. A sample of 522 patients was recruited from 84 acute psychiatric wards in 31 hospital locations in London and the surrounding areas during 2009-2010. Data on the order of conflict and containment events were collected for the first two weeks of admission from patients' case notes. Event-to-event transitions were tabulated and depicted diagrammatically. Event types were tested for their most common temporal placing in sequences of events. Most conflict and containment occurs within and between events of the minimal triangle (verbal aggression, de-escalation, and PRN medication), and the majority of these event sequences conclude in no further events; a minority transition to other, more severe, events. Verbal abuse and medication refusal were more likely to start sequences of disturbed behaviour. Training in the prevention and management of violence needs to acknowledge that a gradual escalation of patient behaviour does not always occur. Verbal aggression is a critical initiator of conflict events, and requires more detailed and sustained research on optimal management and prevention strategies. Similar research is required into medication refusal by inpatients. PMID:23875553

  15. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis.

    PubMed

    Amiel, Aldine R; Johnston, Hereroa T; Nedoncelle, Karine; Warner, Jacob F; Ferreira, Solène; Röttinger, Eric

    2015-01-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation. PMID:26633371

  16. Characterization of Morphological and Cellular Events Underlying Oral Regeneration in the Sea Anemone, Nematostella vectensis

    PubMed Central

    Amiel, Aldine R.; Johnston, Hereroa T.; Nedoncelle, Karine; Warner, Jacob F.; Ferreira, Solène; Röttinger, Eric

    2015-01-01

    Cnidarians, the extant sister group to bilateria, are well known for their impressive regenerative capacity. The sea anemone Nematostella vectensis is a well-established system for the study of development and evolution that is receiving increased attention for its regenerative capacity. Nematostella is able to regrow missing body parts within five to six days after its bisection, yet studies describing the morphological, cellular, and molecular events underlying this process are sparse and very heterogeneous in their experimental approaches. In this study, we lay down the basic framework to study oral regeneration in Nematostella vectensis. Using various imaging and staining techniques we characterize in detail the morphological, cellular, and global molecular events that define specific landmarks of this process. Furthermore, we describe in vivo assays to evaluate wound healing success and the initiation of pharynx reformation. Using our described landmarks for regeneration and in vivo assays, we analyze the effects of perturbing either transcription or cellular proliferation on the regenerative process. Interestingly, neither one of these experimental perturbations has major effects on wound closure, although they slightly delay or partially block it. We further show that while the inhibition of transcription blocks regeneration in a very early step, inhibiting cellular proliferation only affects later events such as pharynx reformation and tentacle elongation. PMID:26633371

  17. Application of a new cellular model for bedload transporting extreme events at steep slopes

    NASA Astrophysics Data System (ADS)

    Chiari, M.; Scheidl, C.

    2015-10-01

    A cellular model for bedload transport at steep channel gradients and alluvial fans has been developed to simulate lateral distribution of erosion and deposition on alluvial fans of mountain streams. The cellular model, named FluviSed, applies a quasi-steady-state routing of a flood hydrograph over a rectangular grid. Bedload transport is calculated and the morphological changes are updated after each time step. FluviSed is designed to complement existing one-dimensional bedload transport simulation tools by using their outcome as an input for the simulation of inundated areas. The model has been evaluated against TomSed, a one-dimensional bedload transport model. Further, a back-calculation of a laboratory bedload experiment and a real flood event from 2005 at Schnannerbach in Austria are provided to test the model's suitability for reproducing morphological changes caused by flood events at high channel gradients.

  18. Commonly consumed and specialty dietary mushrooms reduce cellular proliferation in MCF-7 human breast cancer cells.

    PubMed

    Martin, Keith R; Brophy, Sara K

    2010-11-01

    Worldwide, over one million women will be newly diagnosed with breast cancer in the next year. Moreover, breast cancer is the second leading cause of cancer death in the USA. An accumulating body of evidence suggests that consumption of dietary mushrooms can protect against breast cancer. In this study, we tested and compared the ability of five commonly consumed or specialty mushrooms to modulate cell number balance in the cancer process using MCF-7 human breast cancer cells. Hot water extracts (80°C for 2 h) of maitake (MT, Grifola frondosa), crimini (CRIM, Agaricus bisporus), portabella (PORT, Agaricus bisporus), oyster (OYS, Pleurotus ostreatus) and white button (WB, Agaricus bisporus) mushrooms or water alone (5% v/v) were incubated for 24 h with MCF-7 cells. Cellular proliferation determined by bromodeoxyuridine incorporation was significantly (P < 0.05) reduced up to 33% by all mushrooms, with MT and OYS being the most effective. MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) reduction, an often used mitochondrion-dependent marker of proliferation, was unchanged although decreased (P > 0.05) by 15% with OYS extract. Lactate dehydrogenase release, as a marker of necrosis, was significantly increased after incubation with MT but not with other test mushrooms. Furthermore, MT extract significantly increased apoptosis, or programmed cell death, as determined by terminal deoxynucleotidyl end labeling method, whereas other test mushrooms displayed trends of ∼15%. The total numbers of cells per flask, determined by hemacytometry, were not different from control cultures. Overall, all test mushrooms significantly suppressed cellular proliferation, with MT further significantly inducing apoptosis and cytotoxicity in human breast cancer cells. This suggests that both common and specialty mushrooms may be chemoprotective against breast cancer. PMID:20921274

  19. Grading dermatologic adverse events of cancer treatments: the Common Terminology Criteria for Adverse Events Version 4.0.

    PubMed

    Chen, Alice P; Setser, Ann; Anadkat, Milan J; Cotliar, Jonathan; Olsen, Elise A; Garden, Benjamin C; Lacouture, Mario E

    2012-11-01

    Dermatologic adverse events to cancer therapies have become more prevalent and may to lead to dose modifications or discontinuation of life-saving or prolonging treatments. This has resulted in a new collaboration between oncologists and dermatologists, which requires accurate cataloging and grading of side effects. The Common Terminology Criteria for Adverse Events Version 4.0 is a descriptive terminology and grading system that can be used for uniform reporting of adverse events. A proper understanding of this standardized classification system is essential for dermatologists to properly communicate with all physicians caring for patients with cancer. PMID:22502948

  20. TSQ, a Common Fluorescent Sensor for Cellular Zinc, Images Zinc Proteins

    PubMed Central

    Meeusen, Jeffrey W.; Tomasiewicz, Henry; Nowakowski, Andrew; Petering, David H.

    2011-01-01

    Zn2+ is a necessary cofactor for thousands of mammalian proteins. Research has suggested that transient fluxes of cellular Zn2+ are also involved in processes such as apoptosis. Observations of Zn2+ trafficking have been collected using Zn2+ responsive fluorescent dyes. A commonly used Zn2+ fluorophore is TSQ. The chemical species responsible for TSQ's observed fluorescence in resting or activated cells have not been characterized. Parallel fluorescence microscopy and spectrofluorometry of LLC-PK1 cells incubated with TSQ demonstrated punctate staining that concentrated around the nucleus and was characterized by an emission maximum near 470 nm. Addition of cell permeable Zn-pyrithione resulted in greatly increased, diffuse fluorescence that shifted the emission peak to 490 nm, indicative of the formation of Zn(TSQ)2. TPEN, a cell permeant Zn2+ chelator, largely quenched TSQ fluorescence returning the residual fluorescence to the 470 nm emission maximum. Gel filtration chromatography of cell supernatant from LLC-PK1 cells treated with TSQ revealed that TSQ fluorescence (470 nm emission) eluted with the proteome fractions. Similarly, addition of TSQ to proteome prior to chromatography resulted in 470 nm fluorescence emission that was not observed in smaller molecular weight fractions. It is hypothesized that Zn-TSQ fluorescence, blue-shifted from the 490 nm emission maximum of Zn(TSQ)2, results from ternary complex, TSQ-Zn-protein formation. As an example, Zn-carbonic anhydrase formed a ternary adduct with TSQ characterized by a fluorescence emission maximum of 470 nm and a dissociation constant of 1.55 × 10-7 M. Quantification of TSQ-Zn-proteome fluorescence indicated that approximately 8% of cellular Zn2+ was imaged by TSQ. These results were generalized to other cell types and model Zn-proteins. PMID:21774459

  1. Cellular and Deafness Mechanisms Underlying Connexin Mutation-Induced Hearing Loss – A Common Hereditary Deafness

    PubMed Central

    Wingard, Jeffrey C.; Zhao, Hong-Bo

    2015-01-01

    Hearing loss due to mutations in the connexin gene family, which encodes gap junctional proteins, is a common form of hereditary deafness. In particular, connexin 26 (Cx26, GJB2) mutations are responsible for ~50% of non-syndromic hearing loss, which is the highest incidence of genetic disease. In the clinic, Cx26 mutations cause various auditory phenotypes ranging from profound congenital deafness at birth to mild, progressive hearing loss in late childhood. Recent experiments demonstrate that congenital deafness mainly results from cochlear developmental disorders rather than hair cell degeneration and endocochlear potential reduction, while late-onset hearing loss results from reduction of active cochlear amplification, even though cochlear hair cells have no connexin expression. However, there is no apparent, demonstrable relationship between specific changes in connexin (channel) functions and the phenotypes of mutation-induced hearing loss. Moreover, new experiments further demonstrate that the hypothesized K+-recycling disruption is not a principal deafness mechanism for connexin deficiency induced hearing loss. Cx30 (GJB6), Cx29 (GJC3), Cx31 (GJB3), and Cx43 (GJA1) mutations can also cause hearing loss with distinct pathological changes in the cochlea. These new studies provide invaluable information about deafness mechanisms underlying connexin mutation-induced hearing loss and also provide important information for developing new protective and therapeutic strategies for this common deafness. However, the detailed cellular mechanisms underlying these pathological changes remain unclear. Also, little is known about specific mutation-induced pathological changes in vivo and little information is available for humans. Such further studies are urgently required. PMID:26074771

  2. Monitoring Cellular Events in Living Mast Cells Stimulated with an Extremely Small Amount of Fluid on a Microchip

    NASA Astrophysics Data System (ADS)

    Munaka, Tatsuya; Abe, Hirohisa; Kanai, Masaki; Sakamoto, Takashi; Nakanishi, Hiroaki; Yamaoka, Tetsuji; Shoji, Shuichi; Murakami, Akira

    2006-07-01

    We successfully developed a measurement system for real-time analysis of cellular function using a newly designed microchip. This microchip was equipped with a micro cell incubation chamber (240 nl) and was stimulated by a very small amount of stimuli (as small as 24 nl). Using the microchip system, cultivation of mast cells was successfully carried out. Monitoring of the cellular events after stimulation with an extremely small amount of fluid on a microchip was performed. This system could be applicable for various types of cellular analysis including real-time monitoring of cellular response by stimulation.

  3. Photosynthetic sensitivity of phytoplankton to commonly used pharmaceuticals and its dependence on cellular phosphorus status.

    PubMed

    Grzesiuk, Malgorzata; Wacker, Alexander; Spijkerman, Elly

    2016-05-01

    Recently pharmaceuticals have become significant environmental pollutants in aquatic ecosystems, that could affect primary producers such as microalgae. Here we analyzed the effect of pharmaceuticals on the photosynthesis of microalgae commonly found in freshwater-two species of Chlorophyceae and a member of the Eustigmatophyceae, via PAM fluorometry. As pharmaceuticals, three medicines often consumed in households were chosen: (i) fluoxetine, an antidepressant, (ii) propranolol, a β-blocker and (iii) ibuprofen, an anti-inflammatory and analgesic medicine. The EC50 for the quantum yield of photosystem II in phytoplankton acclimated to inorganic phosphorus (Pi)-replete and Pi-limited conditions was estimated. Acute toxicity experiments over a 5 h exposure revealed that Nannochloropsis limnetica was the least sensitive to pharmaceuticals in its photosynthetic yield out of all species tested. Although the estimation of sub-lethal effects can be vital in contrast to that of LC50s, the EC50 values in all species and for all medicines were orders of magnitude higher than concentrations found in polluted surface water. Chlamydomonas reinhardtii was the most sensitive to fluoxetine (EC50 of 1.6 mg L(-1)), and propranolol (EC50 of 3 mg L(-1)). Acutodesmus obliquus was most sensitive to ibuprofen (EC50 of 288 mg L(-1)). Additionally, the sensitivity to the pharmaceuticals changed under a Pi-limitation; the green algae became less sensitive to fluoxetine and propranolol. In contrast, Pi-limited algal species were more sensitive to ibuprofen. Our results suggest that the sensitivity of algae to pharmaceuticals is (i) highly compound- and species-specific and (ii) dependent on the cellular P status. PMID:26894612

  4. Induction of Autophagy in Porcine Kidney Cells by Quantum Dots: A Common Cellular Response to Nanomaterials?

    PubMed Central

    Stern, Stephan T.; Zolnik, Banu S.; McLeland, Christopher B.; Clogston, Jeffery; Zheng, Jiwen; McNeil, Scott E.

    2008-01-01

    Quantum dots (QDs) are being investigated as novel in vivo imaging agents. The leaching of toxic metals from these QDs in biological systems is of great concern. This study compared the cytotoxic mechanisms of two QD species made of different core materials (cadmium selenide [CdSe] vs. indium gallium phosphide [InGaP]) but similar core sizes (5.1 vs. 3.7 nm) and surface compositions (both ZnS capped, lipid-coated and pegylated). The CdSe QD was found to be 10-fold more toxic to porcine renal proximal tubule cells (LLC-PK1) than the InGaP QD on a molar basis, as determined by MTT assay (48 h IC50 10nM for CdSe vs. 100nM for InGaP). Neither of the QD species induced appreciable oxidative stress, as determined by lipid peroxide and reduced glutathione content, suggesting that toxicity was not metal associated. In agreement, treatment of cells with CdSe QDs was not associated with changes in metallothionein-IA (MT-IA) gene expression or Cd-associated caspase 3 enzyme activation. By contrast, incubation of the LLC-PK1 cells with the InGaP QD resulted in a dramatic increase in MT-IA expression by 21- and 43-fold, at 8 and 24 h, respectively. The most remarkable finding was evidence of extensive autophagy in QD-treated cells, as determined by Lysotracker Red dye uptake, TEM, and LC3 immunobloting. Autophagy induction has also been described for other nanomaterials and may represent a common cellular response. These data suggest that QD cytotoxicity is dependent upon properties of the particle as a whole, and not exclusively the metal core materials. PMID:18632727

  5. On the possible common nature of double extensive air showers and aligned events

    SciTech Connect

    Yakovlev, V. I.

    2012-07-15

    Double extensive air showers and aligned events at energies in the region E Greater-Than-Or-Equivalent-To 10{sup 16} eV were discovered more than a quarter of a century ago. However, there is still no satisfactory explanation of their nature. In the present study, it is assumed that these two types of events have common nature, stemming from the break of a string that arises in the interaction of ultrahigh-energy particles.

  6. A database of common-cause events for risk and reliability applications

    SciTech Connect

    Fleming, K.N.; Rao, S.B. )

    1992-06-01

    This report documents a common cause event database and updates an earlier version of a database that was published as EPRI report NP-3967 in June 1985. The purposes of this report are to provide more information on the original set of common cause events, to expand on both the number of events and the coverage of different component types, and to provide guidance in how to use the database to support applied risk and reliability evaluations such as the ongoing individual plant examination (IPE). Included in this report are descriptions and analyses of events that were found to be of potential importance in a common cause analysis, statistical information from which to estimate common cause failure probabilities, and examples of how the information can be used to support a plant-specific probabilistic risk assessment (PRA) or reliability evaluation, according to the PRA Procedures for Common Cause Analysis documented in NUREG/CR-4780. That procedures guide, which was developed under joint sponsorship of EPRI and the US Nuclear Regulatory Commission, was supported by EPRI research project RP2169-4.

  7. A database of common-cause events for risk and reliability applications. Final report

    SciTech Connect

    Fleming, K.N.; Rao, S.B.

    1992-06-01

    This report documents a common cause event database and updates an earlier version of a database that was published as EPRI report NP-3967 in June 1985. The purposes of this report are to provide more information on the original set of common cause events, to expand on both the number of events and the coverage of different component types, and to provide guidance in how to use the database to support applied risk and reliability evaluations such as the ongoing individual plant examination (IPE). Included in this report are descriptions and analyses of events that were found to be of potential importance in a common cause analysis, statistical information from which to estimate common cause failure probabilities, and examples of how the information can be used to support a plant-specific probabilistic risk assessment (PRA) or reliability evaluation, according to the PRA Procedures for Common Cause Analysis documented in NUREG/CR-4780. That procedures guide, which was developed under joint sponsorship of EPRI and the US Nuclear Regulatory Commission, was supported by EPRI research project RP2169-4.

  8. Common-Cause Failure Treatment in Event Assessment: Basis for a Proposed New Model

    SciTech Connect

    Dana Kelly; Song-Hua Shen; Gary DeMoss; Kevin Coyne; Don Marksberry

    2010-06-01

    Event assessment is an application of probabilistic risk assessment in which observed equipment failures and outages are mapped into the risk model to obtain a numerical estimate of the event’s risk significance. In this paper, we focus on retrospective assessments to estimate the risk significance of degraded conditions such as equipment failure accompanied by a deficiency in a process such as maintenance practices. In modeling such events, the basic events in the risk model that are associated with observed failures and other off-normal situations are typically configured to be failed, while those associated with observed successes and unchallenged components are assumed capable of failing, typically with their baseline probabilities. This is referred to as the failure memory approach to event assessment. The conditioning of common-cause failure probabilities for the common cause component group associated with the observed component failure is particularly important, as it is insufficient to simply leave these probabilities at their baseline values, and doing so may result in a significant underestimate of risk significance for the event. Past work in this area has focused on the mathematics of the adjustment. In this paper, we review the Basic Parameter Model for common-cause failure, which underlies most current risk modelling, discuss the limitations of this model with respect to event assessment, and introduce a proposed new framework for common-cause failure, which uses a Bayesian network to model underlying causes of failure, and which has the potential to overcome the limitations of the Basic Parameter Model with respect to event assessment.

  9. Sustaining Public Education Events through Partnerships: Joining Forces for a Common Goal

    NASA Astrophysics Data System (ADS)

    McCall, L. R.; Clift, S.; Moore, S. L.

    2015-12-01

    Well-designed public STEM events benefit both the subject matter experts and the broader community. But planning and conducting these events costs participants' time and energy. For 15 years, the Bureau of Economic Geology of The University of Texas at Austin has hosted an Austin Earth Science Week Career Day, in which STEM professionals showcase their knowledge, skills, and experiences for middle-school students. By establishing partnerships and assuming a leadership role, the Bureau has leveraged resources to host a sustainable series of educational events. Key to success was finding a common goal that all participants were interested in fulfilling. Engaging and educating students about careers in geoscience became that unifying goal. Governmental agency staffers, industry professionals, graduate students, and school administrators were all interested in this effort. The career theme also attracted a wide variety of professionals, many of whom have participated in the event every year. The biggest challenge is meeting the demand from schools for this type of educational experience. In early years, the event was hosted by a few Bureau scientists in their offices. As word spread about the event, new partners and a larger facility were required to accommodate the growing number of participants. Currently, new media and distance learning platforms are being explored for broadening the event to meet demand. After 15 years, the Austin Earth Science Week Career Day has now become a tradition. We hope it serves as a model to others interested in establishing a STEM event in their own community.

  10. Overexpression of cellular inhibitor of apoptosis protein 2 is an early event in the progression of pancreatic cancer

    PubMed Central

    Esposito, Irene; Kleeff, Jörg; Abiatari, Ivane; Shi, Xined; Giese, Nathalia; Bergmann, Frank; Roth, Wilfried; Friess, Helmut; Schirmacher, Peter

    2007-01-01

    Aim To determine the role of two antiapoptotic proteins of the inhibitor of apoptosis protein family, cellular inhibitor of apoptosis protein 1 (cIAP1) and cellular inhibitor of apoptosis protein 2 (cIAP2), in human pancreatic carcinogenesis. Methods mRNA levels were measured in pancreatic tissues and pancreatic cancer cell lines by quantitative reverse transcriptase PCR. Protein expression was assessed in pancreatic cancer cell lines by immunoblotting and in pancreatic tissues by immunohistochemistry, and correlated with pathological and survival data. Results cIAP1 expression was constantly high in non‐neoplastic pancreatic tissues, in pancreatic intraepithelial neoplasia (PanIN) lesions, as well as in a subset of primary and metastatic pancreatic ductal adenocarcinomas (PDAC), and a preferential cytoplasmatic localisation was observed in the tumour tissues. cIAP1 expression was rare in a cohort of cystic tumours. cIAP2 mRNA levels were significantly higher (2.4 fold) in PDAC than in normal tissues. cIAP2 protein was overexpressed in PDAC, and was detectable in low‐ and high‐grade PanIN lesions. Moreover, cIAP2 was often expressed in pancreatic cystic tumours. cIAP1 and cIAP2 mRNA and protein were detected in all the examined cell lines. Survival analysis revealed a shorter survival in patients with cIAP1/cIAP2‐positive tumours. Conclusions cIAP1 might contribute to the regulation of the apoptotic process in the normal and in the neoplastic pancreas, depending on its subcellular localisation. Overexpression of cIAP2 is a common and early event in the progression of pancreatic cancer, and could therefore potentially influence the important pathophysiological aspects of PDAC, such as anoikis or chemoresistance. PMID:16775116

  11. Molecular and Cellular Events Mediating Glomerular Podocyte Dysfunction and Depletion in Diabetes Mellitus

    PubMed Central

    Anil Kumar, P.; Welsh, Gavin I.; Saleem, Moin A.; Menon, Ram K.

    2014-01-01

    The essential function of the kidney is to ensure formation of a relatively protein-free ultra-filtrate, urine. The rate of filtration and composition of the primary renal filtrate is determined by the transport of fluid and solutes across the glomerular filtration barrier consisting of endothelial cells, the glomerular basement membrane, and podocyte foot processes. In diabetes mellitus (DM), components of the kidney that enable renal filtration get structurally altered and functionally compromised resulting in proteinuria that often progresses to end-stage renal disease. Histological alterations in DM include early hypertrophy of glomerular and tubular components, subsequent thickening of basement membrane in glomeruli and tubules, progressive accumulation of extracellular matrix proteins in the glomerular mesangium and loss of podocytes, together constituting a clinical condition referred to as diabetic nephropathy (DN). The glomerulus has become the focus of research investigating the mechanism of proteinuria. In particular, the progressive dysfunction and/or loss of podocytes that is contemporaneous with proteinuria in DN have attracted intense scientific attention. The absolute number of podocytes predicts glomerular function and podocyte injury is a hallmark of various glomerular diseases. This review discusses the importance of podocytes in normal renal filtration and details the molecular and cellular events that lead to podocyte dysfunction and decreased podocyte count in DN. PMID:25309512

  12. Common envelope events with low-mass giants: understanding the energy budget

    NASA Astrophysics Data System (ADS)

    Nandez, J. L. A.; Ivanova, N.

    2016-08-01

    Common envelope events are important interactions between two binary stars that lead to the formation of close binary systems. We present here a systematic three-dimensional study in which we model common envelope events with low-mass giant donors. The results allow us to revise the energy formalism that is usually used to determine common envelope event outcomes. We show that the energy budget for this type of system should include the recombination energy, and that it also must take into account that a significant fraction of the released orbital energy is taken away by the ejecta. We provide three ways in which our results can be used by binary population synthesis studies: a relation that links the observed post-common envelope binary with the initial binary parameters, a fitting formula for the $\\alpha_{\\rm ce}\\lambda$ parameter of the standard energy formalism, and a revised energy formalism that takes into account both the recombination energy and the energy that is taken away by the ejecta.

  13. Common envelope events with low-mass giants: understanding the energy budget

    NASA Astrophysics Data System (ADS)

    Nandez, J. L. A.; Ivanova, N.

    2016-08-01

    Common envelope events are important interactions between two binary stars that lead to the formation of close binary systems. We present here a systematic three-dimensional study in which we model common envelope events with low-mass giant donors. The results allow us to revise the energy formalism that is usually used to determine common envelope event outcomes. We show that the energy budget for this type of system should include the recombination energy, and that it also must take into account that a significant fraction of the released orbital energy is taken away by the ejecta. We provide three ways in which our results can be used by binary population synthesis studies: a relation that links the observed post-common envelope binary with the initial binary parameters, a fitting formula for the αceλ parameter of the standard energy formalism, and a revised energy formalism that takes into account both the recombination energy and the energy that is taken away by the ejecta.

  14. Common envelope events with low-mass giants: understanding the energy budget

    NASA Astrophysics Data System (ADS)

    Nandez, J. L. A.; Ivanova, N.

    2016-05-01

    Common envelope events are important interactions between two binary stars that lead to the formation of close binary systems. We present here a systematic three-dimensional study in which we model common envelope events with low-mass giant donors. The results allow us to revise the energy formalism that is usually used to determine common envelope event outcomes. We show that the energy budget for this type of system should include the recombination energy, and that it also must take into account that a significant fraction of the released orbital energy is taken away by the ejecta. We provide three ways in which our results can be used by binary population synthesis studies: a relation that links the observed post-common envelope binary with the initial binary parameters, a fitting formula for the αceλ parameter of the standard energy formalism, and a revised energy formalism that takes into account both the recombination energy and the energy that is taken away by the ejecta.

  15. The effect of bisphosphonate treatment on the biochemical and cellular events during bone remodelling in response to microinjury stimulation.

    PubMed

    Mulcahy, L E; Curtin, C M; McCoy, R J; O'Brien, F J; Taylor, D; Lee, T C; Duffy, G P

    2015-01-01

    Osteoporosis is one of the most prevalent bone diseases worldwide and is characterised by high levels of bone turnover, a marked loss in bone mass and accumulation of microdamage, which leads to an increased fracture incidence that places a huge burden on global health care systems. Bisphosphonates have been used to treat osteoporosis and have shown great success in conserving bone mass and reducing fracture incidence. In spite of the existing knowledge of the in vivo responses of bone to bisphosphonates, the cellular responses to these drugs have yet to be fully elucidated. In vitro model systems that allow the decoupling of complex highly integrated events, such as bone remodelling, provide a tool whereby these biological processes may be studied in a more simplified context. This study firstly utilised an in vitro model system of bone remodelling and comprising all three major cell types of the bone (osteocytes, osteoclasts and osteoblasts), which was representative of the bone's capacity to sense microdamage and subsequently initiate a basic multicellular unit response. Secondly, this system was used to study the effect of two commonly utilised aminobisphosphonate treatments for osteoporosis, alendronate and zoledronate. We demonstrated that microinjury to osteocyte networks being treated with bisphosphonates modulates receptor activator of nuclear factor kappa-B ligand and osteoprotegerin activity, and subsequently osteoclastogenesis. Furthermore, bisphosphonates increased the osteogenic potential following microinjury. Thus, we have shown for the first time that bisphosphonates act at all three stages of bone remodelling, from microinjury to osteoclastogenesis and ultimately osteogenesis. PMID:26614482

  16. Common Genetic Variation In Cellular Transport Genes and Epithelial Ovarian Cancer (EOC) Risk

    PubMed Central

    Chornokur, Ganna; Lin, Hui-Yi; Tyrer, Jonathan P.; Lawrenson, Kate; Dennis, Joe; Amankwah, Ernest K.; Qu, Xiaotao; Tsai, Ya-Yu; Jim, Heather S. L.; Chen, Zhihua; Chen, Ann Y.; Permuth-Wey, Jennifer; Aben, Katja KH.; Anton-Culver, Hoda; Antonenkova, Natalia; Bruinsma, Fiona; Bandera, Elisa V.; Bean, Yukie T.; Beckmann, Matthias W.; Bisogna, Maria; Bjorge, Line; Bogdanova, Natalia; Brinton, Louise A.; Brooks-Wilson, Angela; Bunker, Clareann H.; Butzow, Ralf; Campbell, Ian G.; Carty, Karen; Chang-Claude, Jenny; Cook, Linda S.; Cramer, Daniel W.; Cunningham, Julie M.; Cybulski, Cezary; Dansonka-Mieszkowska, Agnieszka; du Bois, Andreas; Despierre, Evelyn; Dicks, Ed; Doherty, Jennifer A.; Dörk, Thilo; Dürst, Matthias; Easton, Douglas F.; Eccles, Diana M.; Edwards, Robert P.; Ekici, Arif B.; Fasching, Peter A.; Fridley, Brooke L.; Gao, Yu-Tang; Gentry-Maharaj, Aleksandra; Giles, Graham G.; Glasspool, Rosalind; Goodman, Marc T.; Gronwald, Jacek; Harrington, Patricia; Harter, Philipp; Hein, Alexander; Heitz, Florian; Hildebrandt, Michelle A. T.; Hillemanns, Peter; Hogdall, Claus K.; Hogdall, Estrid; Hosono, Satoyo; Jakubowska, Anna; Jensen, Allan; Ji, Bu-Tian; Karlan, Beth Y.; Kelemen, Linda E.; Kellar, Mellissa; Kiemeney, Lambertus A.; Krakstad, Camilla; Kjaer, Susanne K.; Kupryjanczyk, Jolanta; Lambrechts, Diether; Lambrechts, Sandrina; Le, Nhu D.; Lee, Alice W.; Lele, Shashi; Leminen, Arto; Lester, Jenny; Levine, Douglas A.; Liang, Dong; Lim, Boon Kiong; Lissowska, Jolanta; Lu, Karen; Lubinski, Jan; Lundvall, Lene; Massuger, Leon F. A. G.; Matsuo, Keitaro; McGuire, Valerie; McLaughlin, John R.; McNeish, Iain; Menon, Usha; Milne, Roger L.; Modugno, Francesmary; Moysich, Kirsten B.; Ness, Roberta B.; Nevanlinna, Heli; Eilber, Ursula; Odunsi, Kunle; Olson, Sara H.; Orlow, Irene; Orsulic, Sandra; Weber, Rachel Palmieri; Paul, James; Pearce, Celeste L.; Pejovic, Tanja; Pelttari, Liisa M.; Pike, Malcolm C.; Poole, Elizabeth M.; Risch, Harvey A.; Rosen, Barry; Rossing, Mary Anne; Rothstein, Joseph H.; Rudolph, Anja; Runnebaum, Ingo B.; Rzepecka, Iwona K.; Salvesen, Helga B.; Schernhammer, Eva; Schwaab, Ira; Shu, Xiao-Ou; Shvetsov, Yurii B.; Siddiqui, Nadeem; Sieh, Weiva; Song, Honglin; Southey, Melissa C.; Spiewankiewicz, Beata; Sucheston, Lara; Teo, Soo-Hwang; Terry, Kathryn L.; Thompson, Pamela J.; Thomsen, Lotte; Tangen, Ingvild L.; Tworoger, Shelley S.; van Altena, Anne M.; Vierkant, Robert A.; Vergote, Ignace; Walsh, Christine S.; Wang-Gohrke, Shan; Wentzensen, Nicolas; Whittemore, Alice S.; Wicklund, Kristine G.; Wilkens, Lynne R.; Wu, Anna H.; Wu, Xifeng; Woo, Yin-Ling; Yang, Hannah; Zheng, Wei; Ziogas, Argyrios; Hasmad, Hanis N.; Berchuck, Andrew; Iversen, Edwin S.; Schildkraut, Joellen M.; Ramus, Susan J.; Goode, Ellen L.; Monteiro, Alvaro N. A.; Gayther, Simon A.; Narod, Steven A.; Pharoah, Paul D. P.; Sellers, Thomas A.; Phelan, Catherine M.

    2015-01-01

    Background Defective cellular transport processes can lead to aberrant accumulation of trace elements, iron, small molecules and hormones in the cell, which in turn may promote the formation of reactive oxygen species, promoting DNA damage and aberrant expression of key regulatory cancer genes. As DNA damage and uncontrolled proliferation are hallmarks of cancer, including epithelial ovarian cancer (EOC), we hypothesized that inherited variation in the cellular transport genes contributes to EOC risk. Methods In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons. Results The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4). Conclusion These results, generated on a large cohort of women, revealed associations

  17. Recurrence time statistics of landslide events simulated by a cellular automaton model

    NASA Astrophysics Data System (ADS)

    Piegari, Ester; Di Maio, Rosa; Avella, Adolfo

    2014-05-01

    The recurrence time statistics of a cellular automaton modelling landslide events is analyzed by performing a numerical analysis in the parameter space and estimating Fano factor behaviors. The model is an extended version of the OFC model, which is a paradigm for SOC in non-conserved systems, but it works differently from the original OFC model as a finite value of the driving rate is applied. By driving the system to instability with different rates, the model exhibits a smooth transition from a correlated to an uncorrelated regime as the effect of a change in predominant mechanisms to propagate instability. If the rate at which instability is approached is small, chain processes dominate the landslide dynamics, and power laws govern probability distributions. However, the power-law regime typical of SOC-like systems is found in a range of return intervals that becomes shorter and shorter by increasing the values of the driving rates. Indeed, if the rates at which instability is approached are large, domino processes are no longer active in propagating instability, and large events simply occur because a large number of cells simultaneously reach instability. Such a gradual loss of the effectiveness of the chain propagation mechanism causes the system gradually enter to an uncorrelated regime where recurrence time distributions are characterized by Weibull behaviors. Simulation results are qualitatively compared with those from a recent analysis performed by Witt et al.(Earth Surf. Process. Landforms, 35, 1138, 2010) for the first complete databases of landslide occurrences over a period as large as fifty years. From the comparison with the extensive landslide data set, the numerical analysis suggests that statistics of such landslide data seem to be described by a crossover region between a correlated regime and an uncorrelated regime, where recurrence time distributions are characterized by power-law and Weibull behaviors for short and long return times

  18. Cellular and extracellular dehydration, and angiotensin as stimuli to drinking in the common iguana Iguana iguana.

    PubMed

    Fitzsimons, J T; Kaufman, S

    1977-02-01

    1. After water deprivation, the iguana promptly drank slightly more than enough water to restore the body fluids to isotonicity even under conditions of hypervolaemia. 2. In response to systemic injections of hypertonic solutions of NaCl and sucrose, the iguana drank and retained enough water to dilute the injected load to isotonicity irrespective of whether water was offered immediately or after 3 hr, and irrespective of whether the solute was administered I.V. or I.P. 3. Hypertonic solutions to glucose, urea, sorbitol and KCl caused little drinking. 4. The long latencies to drinking after hypertonic loads, which were not dependent on the nature of the solute, the route of administration or the dosage, were shown not to be a result of slow distribution of the solute throughout the body fluids. 5. Clearance of injected solutes via renal and extra-renal (nasal salt gland) routes was negligible during the 6 hr experimental period. 6. Measurements of plasma [Na], haematocrit, osmotic pressure and inulin space showed that the iguana drank, in response to cellular dehydration, enough water to restore the intracellular fluid volume to normal. 7. We conclude that, in response to substances which dehydrate cells, the iguana regulates its body osmolality precisely and efficiently provided it is able to do so by drinking. In this respect the responses of the iguana are similar to those of the nephrectomized rat since, in the short term, both rely exclusively on drinking to restore cellular water to normal. 8. The iguana also drinks in response to extracellular dehydration produced by hyperoncotic peritoneal dialysis, and in response to I.P. angiotensin II. PMID:850202

  19. Simulation of debris flow events in Sicily by cellular automata model SCIDDICA_SS3

    NASA Astrophysics Data System (ADS)

    Cancelliere, A.; Lupiano, V.; Peres, D. J.; Stancanelli, L.; Avolio, M.; Foti, E.; Di Gregorio, S.

    2013-12-01

    Debris flow models are widely used for hazard mapping or for evaluating the effectiveness of risk mitigation measures. Several models analyze the dynamics of debris flow runout solving Partial Differential Equations. In use of such models, difficulties arise in estimating kinematic geotechnical soil parameters for real phenomena. In order to overcome such difficulties, alternative semi-empirical approaches can be employed, such as macroscopic Cellular Automata (CA). In particular, for CA simulation purposes, the runout of debris flows emerges from local interactions in a dynamical system, subdivided into elementary parts, whose state evolves within a spatial and temporal discretum. The attributes of each cell (substates) describe physical characteristics. For computational reasons, the natural phenomenon is splitted into a number of elementary processes, whose proper composition makes up the CA transition function. By simultaneously applying this function to all the cells, the evolution of the phenomenon can be simulated in terms of modifications of the substates. In this study, we present an application of the macroscopic CA semi-empirical model SCIDDICA_SS3 to the Peloritani Mountains area in Sicily island, Italy. The model was applied using detailed data from the 1 October 2009 debris flow event, which was triggered by a rainfall event of about 250 mm falling in 9 hours, that caused the death of 37 persons. This region is characterized by river valleys with large hillslope angles (30°-60°), catchment basins of small extensions (0.5-12 km2) and soil composed by metamorphic material, which is easy to be eroded. CA usage implies a calibration phase, that identifies an optimal set of parameters capable of adequately play back the considered case, and a validation phase, that tests the model on a sufficient (and different) number of cases similar in terms of physical and geomorphological properties. The performance of the model can be measured in terms of a fitness

  20. Approaches to Manipulating the Dimensionality and Physicochemical Properties of Common Cellular Scaffolds

    PubMed Central

    Bajpai, Saumendra; Kim, Na Young; Reinhart-King, Cynthia A.

    2011-01-01

    A major hurdle in studying biological systems and administering effective tissue engineered therapies is the lack of suitable cell culture models that replicate the dynamic nature of cell-microenvironment interactions. Advances in the field of surface chemistry and polymer science have allowed researchers to develop novel methodologies to manipulate materials to be extrinsically tunable. Usage of such materials in modeling tissues in vitro has offered valuable insights into numerous cellular processes including motility, invasion, and alterations in cell morphology. Here, we discuss novel techniques devised to more closely mimic cell-tissue interactions and to study cell response to distinct physico-chemical changes in biomaterials, with an emphasis on the manipulation of collagen scaffolds. The benefits and pitfalls associated with using collagen are discussed in the context of strategies proposed to control the engineered microenvironment. Tunable systems such as these offer the ability to alter individual features of the microenvironment in vitro, with the promise that the molecular basis of mechanotransduction in vivo may be laid out in future. PMID:22272094

  1. mFOAM-1.02: A compact version of the cellular event generator FOAM

    NASA Astrophysics Data System (ADS)

    Jadach, S.; Sawicki, P.

    2007-09-01

    The general-purpose self-adapting Monte Carlo (MC) event generator/simulator mFOAM (standing for mini-FOAM) is a new compact version of the FOAM program, with a slightly limited functionality with respect to its parent version. On the other hand, mFOAM is easier to use for the average user. This new version is fully integrated with the ROOT package, the C++ utility library used widely in the particle physics community. The internal structure of the code is simplified and the very valuable feature of the persistency of the objects of the mFOAM class is improved. With the persistency at hand, it is possible to record very easily the complete state of a MC simulator object based on mFOAM and ROOT into a disk-file at any stage of its use: just after object allocation, after full initialization (exploration of the distribution), or at any time during the generation of the long series of MC events. Later on the MC simulator object can be easily restored from the disk-file in the "ready to go" state. Objects of the TFoam class can be used as a stand-alone solution to many everyday problems in the area of the Monte Carlo simulation, or as building blocks in large-scale MC projects, taking full advantage of the object-oriented technology and persistency. Program summaryManuscript title: mFOAM-1.02: A compact version of the cellular event generator FOAM Authors: S. Jadach, P. Sawicki Program title: mFOAM (mini FOAM), version 1.02 Catalogue identifier: ADYX_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/ADYX_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 2 036 711 No. of bytes in distributed program, including test data, etc.: 21 403 104 Distribution format: tar.gz Programming language: ANSI C++ Computer: Most Unix workstations, supercomputers and PC Operating

  2. Big Events and Risks to Global Substance Using Populations: Unique Threats and Common Challenges.

    PubMed

    Mackey, Tim K; Strathdee, Steffanie A

    2015-01-01

    In this commentary, we review a set of "Big Events" from around the world that have adversely impacted substance using populations by first identifying common thematic areas between them, and then describing the unique challenges faced by the diverse and vulnerable populations impacted. The Big Events reviewed are multifaceted and complex in nature, and include the recent global financial crisis, economic and trade sanctions, political transition and its impact on ethnic minorities, colonialism and indigenous communities, and ecological disasters. All have led to immense trauma, displacement, and disruption to critical healthcare services/treatment for people who use drugs, populations who are left underserved in the midst of these crises. It is our hope that through this comparative assessment, global policymakers will proactively identify Big Events and prioritize the development of interventions and policy that meet the unique and immediate needs of substance using population in order to mitigate the significant negative short- and long-term impacts on global public health. PMID:25723311

  3. The cytotoxicity of polycationic iron oxide nanoparticles: Common endpoint assays and alternative approaches for improved understanding of cellular response mechanism

    PubMed Central

    2012-01-01

    Background Iron oxide magnetic nanoparticles (MNP's) have an increasing number of biomedical applications. As such in vitro characterisation is essential to ensure the bio-safety of these particles. Little is known on the cellular interaction or effect on membrane integrity upon exposure to these MNPs. Here we synthesised Fe3O4 and surface coated with poly(ethylenimine) (PEI) and poly(ethylene glycol) (PEG) to achieve particles of varying surface positive charges and used them as model MNP's to evaluate the relative utility and limitations of cellular assays commonly applied for nanotoxicity assessment. An alternative approach, atomic force microscopy (AFM), was explored for the analysis of membrane structure and cell morphology upon interacting with the MNPs. The particles were tested in vitro on human SH-SY5Y, MCF-7 and U937 cell lines for reactive oxygen species (ROS) production and lipid peroxidation (LPO), LDH leakage and their overall cytotoxic effect. These results were compared with AFM topography imaging carried out on fixed cell lines. Results Successful particle synthesis and coating were characterised using FTIR, PCS, TEM and ICP. The particle size from TEM was 30 nm (−16.9 mV) which increased to 40 nm (+55.6 mV) upon coating with PEI and subsequently 50 nm (+31.2 mV) with PEG coating. Both particles showed excellent stability not only at neutral pH but also in acidic environment of pH 4.6 in the presence of sodium citrate. The higher surface charge MNP-PEI resulted in increased cytotoxic effect and ROS production on all cell lines compared with the MNP-PEI-PEG. In general the effect on the cell membrane integrity was observed only in SH-SY5Y and MCF-7 cells by MNP-PEI determined by LDH leakage and LPO production. AFM topography images showed consistently that both the highly charged MNP-PEI and the less charged MNP-PEI-PEG caused cell morphology changes possibly due to membrane disruption and cytoskeleton remodelling. Conclusions Our findings

  4. Expression of transferrin receptors on mitogen-stimulated human peripheral blood lymphocytes: relation to cellular activation and related metabolic events.

    PubMed Central

    Galbraith, R M; Galbraith, G M

    1981-01-01

    Mitogen-activated normal human peripheral blood lymphocytes bind transferrin to specific membrane receptors. In this study, lymphocytes stimulated with phytohaemagglutinin for 0-66 hr were examined to determine the relation of this phenomenon to cellular activation and related metabolic events. Transferrin receptors were first detected at 20-24 hr. This event was consistently preceded by RNA and protein turnover which commenced during the first 6 hr of culture, whereas initiation of DNA synthesis was detected concurrently with the appearance of receptors or slightly later (24-30 hr). Exposure of cells to inhibitors of RNA and protein synthesis early during culture (at 0 or 24 hr) prevented the expression of transferrin receptors, but also caused generalized metabolic failure, and abrogated cellular activation. In contrast, later addition of these agents at 48 hr did not interfere significantly with the process of activation, but did suppress the terminal increase in receptor-bearing cells observed during the final 18 hr in control cultures lacking inhibitor. After deliberate thermal stripping of receptors from activated cells, the reappearance of membrance binding sites which normally occurred within 30 min, was also blocked by cycloheximide, puromycin and actinomycin D. However, similar inhibition of DNA which was induced by hydroxyurea had much less effect upon both the initial appearance of receptors and their reappearance after ligand-induced depletion. These results demonstrate that the appearance of transferrin receptors upon human lymphocytes is dependent upon cellular activation and requires synthesis of protein and RNA. PMID:6172372

  5. Older Adults' Coping with Negative Life Events: Common Processes of Managing Health, Interpersonal, and Financial/Work Stressors

    ERIC Educational Resources Information Center

    Moos, Rudolf H.; Brennan, Penny L.; Schutte, Kathleen K.; Moos, Bernice S.

    2006-01-01

    This study examined how older adults cope with negative life events in health, interpersonal, and financial/work domains and whether common stress and coping processes hold across these three domains. On three occasions, older adults identified the most severe negative event they faced in the last year and described how they appraised and coped…

  6. TSQ (6-methoxy-8-p-toluenesulfonamido-quinoline), a common fluorescent sensor for cellular zinc, images zinc proteins.

    PubMed

    Meeusen, Jeffrey W; Tomasiewicz, Henry; Nowakowski, Andrew; Petering, David H

    2011-08-15

    Zn(2+) is a necessary cofactor for thousands of mammalian proteins. Research has suggested that transient fluxes of cellular Zn(2+) are also involved in processes such as apoptosis. Observations of Zn(2+) trafficking have been collected using Zn(2+) responsive fluorescent dyes. A commonly used Zn(2+) fluorophore is 6-methoxy-8-p-toluenesulfonamido-quinoline (TSQ). The chemical species responsible for TSQ's observed fluorescence in resting or activated cells have not been characterized. Parallel fluorescence microscopy and spectrofluorometry of LLC-PK(1) cells incubated with TSQ demonstrated punctate staining that concentrated around the nucleus and was characterized by an emission maximum near 470 nm. Addition of cell permeable Zn-pyrithione resulted in greatly increased, diffuse fluorescence that shifted the emission peak to 490 nm, indicative of the formation of Zn(TSQ)(2). TPEN (N,N,N'N'-tetrakis(-)[2-pyridylmethyl]-ethylenediamine), a cell permeant Zn(2+) chelator, largely quenched TSQ fluorescence returning the residual fluorescence to the 470 nm emission maximum. Gel filtration chromatography of cell supernatant from LLC-PK(1) cells treated with TSQ revealed that TSQ fluorescence (470 nm emission) eluted with the proteome fractions. Similarly, addition of TSQ to proteome prior to chromatography resulted in 470 nm fluorescence emission that was not observed in smaller molecular weight fractions. It is hypothesized that Zn-TSQ fluorescence, blue-shifted from the 490 nm emission maximum of Zn(TSQ)(2), results from ternary complex, TSQ-Zn-protein formation. As an example, Zn-carbonic anhydrase formed a ternary adduct with TSQ characterized by a fluorescence emission maximum of 470 nm and a dissociation constant of 1.55 × 10(-7) M. Quantification of TSQ-Zn-proteome fluorescence indicated that approximately 8% of cellular Zn(2+) was imaged by TSQ. These results were generalized to other cell types and model Zn-proteins. PMID:21774459

  7. In situ sensing and modeling of molecular events at the cellular level

    NASA Astrophysics Data System (ADS)

    Yang, Ruiguo

    We developed the Atomic Force Microscopy (AFM) based nanorobot in combination with other nanomechanical sensors for the investigation of cell signaling pathways. The AFM nanorobotics hinge on the superior spatial resolution of AFM in imaging and extends it into the measurement of biological processes and manipulation of biological matters. A multiple input single output control system was designed and implemented to solve the issues of nanomanipulation of biological materials, feedback, response frequency and nonlinearity. The AFM nanorobotic system therefore provide the human-directed position, velocity and force control with high frequency feedback, and more importantly it can feed the operator with the real-time imaging of manipulation result from the fast-imaging based local scanning. The use of the system has taken the study of cellular process at the molecular scale into a new level. The cellular response to the physiological conditions can be significantly manifested in cellular mechanics. Dynamic mechanical property has been regarded as biomarkers, sometimes even regulators of the signaling and physiological processes, thus the name mechanobiology. We sought to characterize the relationship between the structural dynamics and the molecular dynamics and the role of them in the regulation of cell behavior. We used the AFM nanorobotics to investigate the mechanical properties in real-time of cells that are stimulated by different chemical species. These reagents could result in similar ion channel responses but distinctive mechanical behaviors. We applied these measurement results to establish a model that describes the cellular stimulation and the mechanical property change, a "two-hit" model that comprises the loss of cell adhesion and the initiation of cell apoptosis. The first hit was verified by functional experiments: depletion of Calcium and nanosurgery to disrupt the cellular adhesion. The second hit was tested by a labeling of apoptotic markers that

  8. Reduction of Cellular Expression Levels Is a Common Feature of Functionally Affected Pendrin (SLC26A4) Protein Variants

    PubMed Central

    de Moraes, Vanessa C S; Bernardinelli, Emanuele; Zocal, Nathalia; Fernandez, Jhonathan A; Nofziger, Charity; Castilho, Arthur M; Sartorato, Edi L; Paulmichl, Markus; Dossena, Silvia

    2016-01-01

    Sequence alterations in the pendrin gene (SLC26A4) leading to functionally affected protein variants are frequently involved in the pathogenesis of syndromic and nonsyndromic deafness. Considering the high number of SLC26A4 sequence alterations reported to date, discriminating between functionally affected and unaffected pendrin protein variants is essential in contributing to determine the genetic cause of deafness in a given patient. In addition, identifying molecular features common to the functionally affected protein variants can be extremely useful to design future molecule-directed therapeutic approaches. Here we show the functional and molecular characterization of six previously uncharacterized pendrin protein variants found in a cohort of 58 Brazilian deaf patients. Two variants (p.T193I and p.L445W) were undetectable in the plasma membrane, completely retained in the endoplasmic reticulum and showed no transport function; four (p.P142L, p.G149R, p.C282Y and p.Q413R) showed reduced function and significant, although heterogeneous, expression levels in the plasma membrane. Importantly, total expression levels of all of the functionally affected protein variants were significantly reduced with respect to the wild-type and a fully functional variant (p.R776C), regardless of their subcellular localization. Interestingly, reduction of expression may also reduce the transport activity of variants with an intrinsic gain of function (p.Q413R). As reduction of overall cellular abundance was identified as a common molecular feature of pendrin variants with affected function, the identification of strategies to prevent reduction in expression levels may represent a crucial step of potential future therapeutic interventions aimed at restoring the transport activity of dysfunctional pendrin variants. PMID:26752218

  9. What Caused the UK's Largest Common Dolphin (Delphinus delphis) Mass Stranding Event?

    PubMed Central

    Jepson, Paul D.; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell Jr., Robert L.; Clare, Frances C.; Davison, Nick; Law, Robin J.; Loveridge, Jan; Macgregor, Shaheed K.; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W.; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L.; Tregenza, Nick; Cunningham, Andrew A.; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06∶30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a “two-stage process” where a group of normally pelagic dolphins entered Falmouth Bay and, after 3–4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID

  10. What caused the UK's largest common dolphin (Delphinus delphis) mass stranding event?

    PubMed

    Jepson, Paul D; Deaville, Robert; Acevedo-Whitehouse, Karina; Barnett, James; Brownlow, Andrew; Brownell, Robert L; Clare, Frances C; Davison, Nick; Law, Robin J; Loveridge, Jan; Macgregor, Shaheed K; Morris, Steven; Murphy, Sinéad; Penrose, Rod; Perkins, Matthew W; Pinn, Eunice; Seibel, Henrike; Siebert, Ursula; Sierra, Eva; Simpson, Victor; Tasker, Mark L; Tregenza, Nick; Cunningham, Andrew A; Fernández, Antonio

    2013-01-01

    On 9 June 2008, the UK's largest mass stranding event (MSE) of short-beaked common dolphins (Delphinus delphis) occurred in Falmouth Bay, Cornwall. At least 26 dolphins died, and a similar number was refloated/herded back to sea. On necropsy, all dolphins were in good nutritive status with empty stomachs and no evidence of known infectious disease or acute physical injury. Auditory tissues were grossly normal (26/26) but had microscopic haemorrhages (5/5) and mild otitis media (1/5) in the freshest cases. Five lactating adult dolphins, one immature male, and one immature female tested were free of harmful algal toxins and had low chemical pollutant levels. Pathological evidence of mud/seawater inhalation (11/26), local tide cycle, and the relative lack of renal myoglobinuria (26/26) suggested MSE onset on a rising tide between 06:30 and 08∶21 hrs (9 June). Potential causes excluded or considered highly unlikely included infectious disease, gas/fat embolism, boat strike, by-catch, predator attack, foraging unusually close to shore, chemical or algal toxin exposure, abnormal weather/climatic conditions, and high-intensity acoustic inputs from seismic airgun arrays or natural sources (e.g., earthquakes). International naval exercises did occur in close proximity to the MSE with the most intense part of the exercises (including mid-frequency sonars) occurring four days before the MSE and resuming with helicopter exercises on the morning of the MSE. The MSE may therefore have been a "two-stage process" where a group of normally pelagic dolphins entered Falmouth Bay and, after 3-4 days in/around the Bay, a second acoustic/disturbance event occurred causing them to strand en masse. This spatial and temporal association with the MSE, previous associations between naval activities and cetacean MSEs, and an absence of other identifiable factors known to cause cetacean MSEs, indicates naval activity to be the most probable cause of the Falmouth Bay MSE. PMID:23646103

  11. Common carotid intima-media thickness relates to cardiovascular events in adults aged <45 years.

    PubMed

    Eikendal, Anouk L M; Groenewegen, Karlijn A; Anderson, Todd J; Britton, Annie R; Engström, Gunnar; Evans, Greg W; de Graaf, Jacqueline; Grobbee, Diederick E; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; Lonn, Eva M; Lorenz, Matthias W; Mathiesen, Ellisiv B; Nijpels, Giel; Dekker, Jacqueline M; Okazaki, Shuhei; O'Leary, Daniel H; Polak, Joseph F; Price, Jacqueline F; Robertson, Christine; Rembold, Christopher M; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T; Sitzer, Matthias; Stehouwer, Coen D A; Hoefer, Imo E; Peters, Sanne A E; Bots, Michiel L; den Ruijter, Hester M

    2015-04-01

    Although atherosclerosis starts in early life, evidence on risk factors and atherosclerosis in individuals aged <45 years is scarce. Therefore, we studied the relationship between risk factors, common carotid intima-media thickness (CIMT), and first-time cardiovascular events in adults aged <45 years. Our study population consisted of 3067 adults aged <45 years free from symptomatic cardiovascular disease at baseline, derived from 6 cohorts that are part of the USE-IMT initiative, an individual participant data meta-analysis of general-population-based cohort studies evaluating CIMT measurements. Information on risk factors, CIMT measurements, and follow-up of the combined end point (first-time myocardial infarction or stroke) was obtained. We assessed the relationship between risk factors and CIMT and the relationship between CIMT and first-time myocardial infarction or stroke using a multivariable linear mixed-effects model and a Cox proportional-hazards model, respectively. During a follow-up of 16.3 years, 55 first-time myocardial infarctions or strokes occurred. Median CIMT was 0.63 mm. Of the risk factors under study, age, sex, diastolic blood pressure, body mass index, total cholesterol, and high-density lipoprotein cholesterol related to CIMT. Furthermore, CIMT related to first-time myocardial infarction or stroke with a hazard ratio of 1.40 per SD increase in CIMT, independent of risk factors (95% confidence interval, 1.11-1.76). CIMT may be a valuable marker for cardiovascular risk in adults aged <45 years who are not yet eligible for standard cardiovascular risk screening. This is especially relevant in those with an increased, unfavorable risk factor burden. PMID:25624341

  12. Association between use of warfarin with common sulfonylureas and serious hypoglycemic events: retrospective cohort analysis

    PubMed Central

    Romley, John A; Gong, Cynthia; Jena, Anupam B; Goldman, Dana P; Williams, Bradley

    2015-01-01

    Study question Is warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride? Methods This was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465 918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4 355 418 person quarters); 71 895 (15.4%) patients also filled a prescription for warfarin (416 479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status. Summary answer and limitations In quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416 479 v 1903/3 938 939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416 479 v 20 759/3 938 939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416 479 v 14 414/3 938 939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and

  13. 77 FR 5857 - Common-Cause Failure Analysis in Event and Condition Assessment: Guidance and Research, Draft...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ...: On November 2, 2011 (76 FR 67764), the U.S. Nuclear Regulatory Commission (NRC) published for public comment Draft NUREG, ``Common- Cause Failure Analysis in Event and Condition Assessment: Guidance and...-2011-0254. Discussion On November 2, 2011 (76 FR 67764), the NRC published for public comment...

  14. 76 FR 67456 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-01

    ..., 2008: 73 FR 70731-70814. AHRQ coordinates the development of a set of common definitions and reporting... March 7, 2011: 76 FR 12358-12359. With this release, AHRQ had made available Common Formats for two... public sector patient safety reporting systems. This inventory provides an evidence base that...

  15. 75 FR 16140 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-31

    ..., 2008: 73 FR 70731-70814. As authorized by the Secretary of HHS, AHRQ coordinates the development of a... Register on September 2, 2009: 74 FR 45457-45458. Definition of Common Formats The term ``Common Formats... private and public sector patient safety reporting systems. This inventory provides an evidence base...

  16. The role of well-defined nanotopography of titanium implants on osseointegration: cellular and molecular events in vivo

    PubMed Central

    Karazisis, Dimitrios; Ballo, Ahmed M; Petronis, Sarunas; Agheli, Hossein; Emanuelsson, Lena; Thomsen, Peter; Omar, Omar

    2016-01-01

    Purpose Mechanisms governing the cellular interactions with well-defined nanotopography are not well described in vivo. This is partly due to the difficulty in isolating a particular effect of nanotopography from other surface properties. This study employed colloidal lithography for nanofabrication on titanium implants in combination with an in vivo sampling procedure and different analytical techniques. The aim was to elucidate the effect of well-defined nanotopography on the molecular, cellular, and structural events of osseointegration. Materials and methods Titanium implants were nanopatterned (Nano) with semispherical protrusions using colloidal lithography. Implants, with and without nanotopography, were implanted in rat tibia and retrieved after 3, 6, and 28 days. Retrieved implants were evaluated using quantitative polymerase chain reaction, histology, immunohistochemistry, and energy dispersive X-ray spectroscopy (EDS). Results Surface characterization showed that the nanotopography was well defined in terms of shape (semispherical), size (79±6 nm), and distribution (31±2 particles/µm2). EDS showed similar levels of titanium, oxygen, and carbon for test and control implants, confirming similar chemistry. The molecular analysis of the retrieved implants revealed that the expression levels of the inflammatory cytokine, TNF-α, and the osteoclastic marker, CatK, were reduced in cells adherent to the Nano implants. This was consistent with the observation of less CD163-positive macrophages in the tissue surrounding the Nano implant. Furthermore, periostin immunostaining was frequently detected around the Nano implant, indicating higher osteogenic activity. This was supported by the EDS analysis of the retrieved implants showing higher content of calcium and phosphate on the Nano implants. Conclusion The results show that Nano implants elicit less periimplant macrophage infiltration and downregulate the early expression of inflammatory (TNF-α) and

  17. 77 FR 22322 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-13

    ... November 21, 2008: 73 FR 70731-70814. The collection of patient safety work product allows the aggregation.... This inventory provides an evidence base that informs construction of the Common Formats. The...

  18. 77 FR 42736 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-20

    ... Federal Register on November 21, 2008: 73 FR 70731-70814. This collection allows the aggregation of... base that informs construction of the Common Formats. The inventory includes many systems from...

  19. 76 FR 12358 - Common Formats for Patient Safety Data Collection and Event Reporting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-07

    ..., 2008: 73 FR 70731-70814. As authorized by the Secretary of HHS, AHRQ coordinates the development of a..., 2009: 74 FR 45457-45458. This release was later replaced by Version 1.1, as announced in the Federal Register on March 31, 2010: 75 FR 16140-16142. Version 1.1 includes updated event descriptions, forms,...

  20. Common stressful life events and difficulties are associated with mental health symptoms and substance use in young adolescents

    PubMed Central

    2012-01-01

    Background Stressful life events are associated with mood disorders in adults in clinical settings. Less described in the literature is the association between common life stressors and a wide range of psychopathology in young adolescents. This study uses a large non-clinical sample of young adolescents to describe the associations among worry or stress about common life events/difficulties, mental health and substance use. Methods Data on lifetime stress or worry about common life events/difficulties (i.e., romantic breakups, family disruption, interpersonal difficulties, and personal stress (health, weight, school work)), symptoms of depression, conduct disorder symptoms, and substance use were collected from 1025 grade 7 students (mean age 12.9 years; 45% male). The association between each source of stress and each mental health and substance use indicator was modeled in separate logistic regression analyses. Results The proportion of adolescents reporting worry or stress ranged from 7% for new family to 53% for schoolwork. Romantic breakup stress was statistically significantly associated with all the mental health and substance use indicators except illicit drug use. Family disruption was statistically significantly associated with depression symptoms, marijuana use, and cigarette use. Interpersonal difficulties stress was statistically significantly associated with depression symptoms. All sources of personal stress were statistically significantly related to depression symptoms. In addition, health-related stress was inversely related to binge drinking. Conclusion Young adolescents may benefit from learning positive coping skills to manage worry or stress about common stressors and in particular, worry or stress related to romantic breakups. Appropriate management of mental health symptoms and substance use related to common stressful life events and difficulties may help reduce emerging psychopathology. PMID:22900789

  1. Emerging proteomic technologies for elucidating context-dependent cellular signaling events: A big challenge of tiny proportions.

    PubMed

    Parker, Sarah J; Raedschelders, Koen; Van Eyk, Jennifer E

    2015-05-01

    Aberrant cell signaling events either drive or compensate for nearly all pathologies. A thorough description and quantification of maladaptive signaling flux in disease is a critical step in drug development, and complex proteomic approaches can provide valuable mechanistic insights. Traditional proteomics-based signaling analyses rely heavily on in vitro cellular monoculture. The characterization of these simplified systems generates a rich understanding of the basic components and complex interactions of many signaling networks, but they cannot capture the full complexity of the microenvironments in which pathologies are ultimately made manifest. Unfortunately, techniques that can directly interrogate signaling in situ often yield mass-limited starting materials that are incompatible with traditional proteomics workflows. This review provides an overview of established and emerging techniques that are applicable to context-dependent proteomics. Analytical approaches are illustrated through recent proteomics-based studies in which selective sample acquisition strategies preserve context-dependent information, and where the challenge of minimal starting material is met by optimized sensitivity and coverage. This review is organized into three major technological themes: (i) LC methods in line with MS; (ii) antibody-based approaches; (iii) MS imaging with a discussion of data integration and systems modeling. Finally, we conclude with future perspectives and implications of context-dependent proteomics. PMID:25545106

  2. Emerging proteomic technologies for elucidating context-dependent cellular signaling events: A big challenge of tiny proportions

    PubMed Central

    Parker, Sarah J; Raedschelders, Koen; Van Eyk, Jennifer E

    2015-01-01

    Aberrant cell signaling events either drive or compensate for nearly all pathologies. A thorough description and quantification of maladaptive signaling flux in disease is a critical step in drug development, and complex proteomic approaches can provide valuable mechanistic insights. Traditional proteomics-based signaling analyses rely heavily on in vitro cellular monoculture. The characterization of these simplified systems generates a rich understanding of the basic components and complex interactions of many signaling networks, but they cannot capture the full complexity of the microenvironments in which pathologies are ultimately made manifest. Unfortunately, techniques that can directly interrogate signaling in situ often yield mass-limited starting materials that are incompatible with traditional proteomics workflows. This review provides an overview of established and emerging techniques that are applicable to context-dependent proteomics. Analytical approaches are illustrated through recent proteomics-based studies in which selective sample acquisition strategies preserve context-dependent information, and where the challenge of minimal starting material is met by optimized sensitivity and coverage. This review is organized into three major technological themes: (1) LC methods inline with mass spectrometry; (2) Antibody-based approaches; (3) MS Imaging with a discussion of data integration and systems modeling. Finally, we conclude with future perspectives and implications of context-dependent proteomics. PMID:25545106

  3. Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen

    PubMed Central

    Wang, Juan-Juan; Qiu, Lei; Cai, Qing; Ying, Sheng-Hua; Feng, Ming-Guang

    2015-01-01

    Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors is likely associated with fungal adaptation to host and environment. Here we show that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1, phases) in unicellular blastospores. Consequently, ΔFkh2 produced twice as many, but smaller, blastospores than wild-type under submerged conditions, and formed denser septa and shorter/broader cells in aberrantly branched hyphae. In these hyphae, clustered genes required for septation and conidiation were remarkedly up-regulated, followed by higher yield and slower germination of aerial conidia. Moreover, ΔFkh2 displayed attenuated virulence and decreased tolerance to chemical and environmental stresses, accompanied with altered transcripts and activities of phenotype-influencing proteins or enzymes. All the changes in ΔFkh2 were restored by Fkh2 complementation. All together, Fkh2-dependent transcriptional control is vital for the adaptation of B. bassiana to diverse habitats of host insects and hence contributes to its biological control potential against arthropod pests. PMID:25955538

  4. Transcriptional control of fungal cell cycle and cellular events by Fkh2, a forkhead transcription factor in an insect pathogen.

    PubMed

    Wang, Juan-Juan; Qiu, Lei; Cai, Qing; Ying, Sheng-Hua; Feng, Ming-Guang

    2015-01-01

    Transcriptional control of the cell cycle by forkhead (Fkh) transcription factors is likely associated with fungal adaptation to host and environment. Here we show that Fkh2, an ortholog of yeast Fkh1/2, orchestrates cell cycle and many cellular events of Beauveria bassiana, a filamentous fungal insect pathogen. Deletion of Fkh2 in B. bassiana resulted in dramatic down-regulation of the cyclin-B gene cluster and hence altered cell cycle (longer G2/M and S, but shorter G0/G1, phases) in unicellular blastospores. Consequently, ΔFkh2 produced twice as many, but smaller, blastospores than wild-type under submerged conditions, and formed denser septa and shorter/broader cells in aberrantly branched hyphae. In these hyphae, clustered genes required for septation and conidiation were remarkedly up-regulated, followed by higher yield and slower germination of aerial conidia. Moreover, ΔFkh2 displayed attenuated virulence and decreased tolerance to chemical and environmental stresses, accompanied with altered transcripts and activities of phenotype-influencing proteins or enzymes. All the changes in ΔFkh2 were restored by Fkh2 complementation. All together, Fkh2-dependent transcriptional control is vital for the adaptation of B. bassiana to diverse habitats of host insects and hence contributes to its biological control potential against arthropod pests. PMID:25955538

  5. The Common Core State Standards Initiative: An Event History Analysis of State Adoption

    ERIC Educational Resources Information Center

    LaVenia, Mark; Cohen-Vogel, Lora; Lang, Laura B.

    2015-01-01

    Today, with states' near-universal adoption of the Common Core State Standards, the political system has achieved that which was not possible less than 2 decades ago. Just why this is so remains unanswered. Some observers have attributed states' embrace of the standards to the substantial financial incentives that the federal government…

  6. On the Nature of EXor Accretion Events: An Infrequent Manifestation of a Common Phenomenology?

    NASA Astrophysics Data System (ADS)

    Lorenzetti, D.; Antoniucci, S.; Giannini, T.; Li Causi, G.; Ventura, P.; Arkharov, A. A.; Kopatskaya, E. N.; Larionov, V. M.; Di Paola, A.; Nisini, B.

    2012-04-01

    We present the results of a comparison between classical and newly identified EXor based on literature data and aimed at recognizing possible differences or similarities between the categories. Optical and near-IR two-color diagrams, modalities of fluctuations, and derived values of the mass accretion rates are indicative of strong similarities between the two samples. We demonstrate how the difference between the outburst and the quiescence spectral energy distribution of all EXor can be well fitted with a single blackbody, as if an additional thermal component appears during the outbursting phase. Temperatures of this additional component span between 1000 and 4500 K, while the radii of the emitting regions (assumed to be a uniform disk) span between 0.01 and 0.1 AU, sizes typical of the inner portions of the circumstellar disk. Spots persisting up to 50% of the outburst duration, not exceeding 10% of the stellar surface, and with temperatures compatible with the EXor mass accretion rates, are able to account for both the appearance of the additional thermal component and the dust sublimation in the inner structures of the disk. We also compare the EXor events with the most significant color and magnitude fluctuations of active T Tauri stars finding that (1) burst accretion phenomena should also be important for this latter class and (2) EXor events could be more frequent than those accidentally discovered. A remarkable case is that of the source V2493 Cyg, a T Tauri star recently identified as a strong outbursting object: New optical and near-IR photometric and spectroscopic data are presented in an attempt to clarify its EXor or FUor nature. Based on observations collected at AZT-24 telescope (Campo Imperatore, Italy), AZT-8 (Crimea, Ukraine), and LX-200 (St. Petersburg, Russia).

  7. Technical note: Common characteristics of directional spreading-steepness joint distribution in freak wave events

    NASA Astrophysics Data System (ADS)

    Liu, Shouhua; Li, Yizhen; Yue, Xinyang

    2016-06-01

    Seven freak wave incidents previously documented in the real ocean in combination with model hindcast simulations are used to study the variations associated with freak-wave-related parameters, such as wave steepness, directional spreading, and frequency bandwidth. Unlike the strong correlations between the freak wave parameters and freak waves' occurrence which were obtained in experimental and physical research, the correlations are not clear in the freak waves occurring in the real ocean. Wave directional spreading-steepness joint distribution is introduced and common visual features were found in the joint distribution when freak waves occur among seven "freakish" sea states. The visual features show that freak wave incidents occur when the steepness is large and directional spreading is small. Besides large steepness and small directional spreading, a long-duration, relatively rough sea state is also necessary for the freak wave generation. The joint distribution is more informative than any single statistical wave parameter. The continuous sea states of local large steepness and small directional spreading are supposed to generate freak waves, and two-dimensional distribution visualization is found to be a useful tool for freak waves' forecast. The common visual features of joint distributions supply an important cue for the theoretical and experimental research.

  8. Dose-response modeling of early molecular and cellular key events in the CAR-mediated hepatocarcinogenesis pathway.

    PubMed

    Geter, David R; Bhat, Virunya S; Gollapudi, B Bhaskar; Sura, Radhakrishna; Hester, Susan D

    2014-04-01

    Low-dose extrapolation and dose-related transitions are paramount in the ongoing debate regarding the quantification of cancer risks for nongenotoxic carcinogens. Phenobarbital (PB) is a prototypical nongenotoxic carcinogen that activates the constitutive androstane receptor (CAR) resulting in rodent liver tumors. In this study, male and female CD-1 mice administered dietary PB at 0, 0.15, 1.5, 15, 75, or 150 mg/kg-day for 2 or 7 days to characterize multiple apical and molecular endpoints below, at (∼75 mg/kg-day), and above the carcinogenic dose level of PB and examine these responses using benchmark dose modeling. Linear toxicokinetics were observed for all doses. Increased liver weight, hepatocellular hypertrophy, and mitotic figures were seen at 75 and 150 mg/kg-day. CAR activation, based on Cyp2b qPCR and pentoxyresorufin dealkylase activity, occurred at doses ≥ 1.5 mg/kg-day. The no-observable transcriptional effect level for global gene expression was 15 mg/kg-day. At 2 days, several xenobiotic metabolism and cell protective pathways were activated at lower doses and to a greater degree in females. However, hepatocellular proliferation, quantified by bromodeoxyuridine immunohistochemistry, was the most sensitive indicator of PB exposure with female mice more sensitive than males, contrary to sex-specific differences in sensitivity to hepatocarcinogenesis. Taken together, the identification of low-dose cellular and molecular transitions in the subtumorigenic dose range aids the understanding of early key events in CAR-mediated hepatocarcinogenesis. PMID:24449422

  9. Stereospecific Inhibitory Effects of CCG-1423 on the Cellular Events Mediated by Myocardin-Related Transcription Factor A

    PubMed Central

    Watanabe, Bunta; Minami, Saki; Ishida, Hideaki; Yoshioka, Ryuzo; Nakagawa, Yoshiaki; Morita, Tsuyoshi; Hayashi, Ken’ichiro

    2015-01-01

    CCG-1423 suppresses several pathological processes including cancer cell migration, tissue fibrosis, and the development of atherosclerotic lesions. These suppressions are caused by inhibition of myocardin-related transcription factor A (MRTF-A), which is a critical factor for epithelial–mesenchymal transition (EMT). CCG-1423 can therefore be a potent inhibitor for EMT. CCG-1423 and related compounds, CCG-100602 and CCG-203971 possess similar biological activities. Although these compounds are comprised of two stereoisomers, the differences in their biological activities remain to be assessed. To address this issue, we stereoselectively synthesized optically pure isomers of these compounds and validated their biological activities. The S-isomer of CCG-1423 rather than the R-isomer exhibited modestly but significantly higher inhibitory effects on the cellular events triggered by MRTF-A activation including serum response factor-mediated gene expression and cell migration of fibroblasts and B16F10 melanoma cells. Accordingly, the S-isomer of CCG-1423 more potently blocked the serum-induced nuclear import of MRTF-A than the R-isomer. No such difference was observed in cells treated with each of two stereoisomers of CCG-100602 or CCG-203971. We previously reported that the N-terminal basic domain (NB), which functions as a nuclear localization signal of MRTF-A, is a binding site for CCG-1423. Consistent with the biological activities of two stereoisomers of CCG-1423, docking simulation demonstrated that the S-isomer of CCG-1423 was more likely to bind to NB than the R-isomer. This is a first report demonstrating the stereospecific biological activities of CCG-1423. PMID:26295164

  10. A beacon of hope in stroke therapy-Blockade of pathologically activated cellular events in excitotoxic neuronal death as potential neuroprotective strategies.

    PubMed

    Hoque, Ashfaqul; Hossain, M Iqbal; Ameen, S Sadia; Ang, Ching-Seng; Williamson, Nicholas; Ng, Dominic C H; Chueh, Anderly C; Roulston, Carli; Cheng, Heung-Chin

    2016-04-01

    Excitotoxicity, a pathological process caused by over-stimulation of ionotropic glutamate receptors, is a major cause of neuronal loss in acute and chronic neurological conditions such as ischaemic stroke, Alzheimer's and Huntington's diseases. Effective neuroprotective drugs to reduce excitotoxic neuronal loss in patients suffering from these neurological conditions are urgently needed. One avenue to achieve this goal is to clearly define the intracellular events mediating the neurotoxic signals originating from the over-stimulated glutamate receptors in neurons. In this review, we first focus on the key cellular events directing neuronal death but not involved in normal physiological processes in the neurotoxic signalling pathways. These events, referred to as pathologically activated events, are potential targets for the development of neuroprotectant therapeutics. Inhibitors blocking some of the known pathologically activated cellular events have been proven to be effective in reducing stroke-induced brain damage in animal models. Notable examples are inhibitors suppressing the ion channel activity of neurotoxic glutamate receptors and those disrupting interactions of specific cellular proteins occurring only in neurons undergoing excitotoxic cell death. Among them, Tat-NR2B9c and memantine are clinically effective in reducing brain damage caused by some acute and chronic neurological conditions. Our second focus is evaluation of the suitability of the other inhibitors for use as neuroprotective therapeutics. We also discuss the experimental approaches suitable for bridging our knowledge gap in our current understanding of the excitotoxic signalling mechanism in neurons and discovery of new pathologically activated cellular events as potential targets for neuroprotection. PMID:26899498

  11. Deletion at Fragile Sites is a Common and Early Event in Barrett’s Esophagus

    PubMed Central

    Lai, Lisa A.; Kostadinov, Rumen; Barrett, Michael T.; Peiffer, Daniel A.; Pokholok, Dimitry; Odze, Robert; Sanchez, Carissa A.; Maley, Carlo C.; Reid, Brian J.; Gunderson, Kevin L.; Rabinovitch, Peter S.

    2011-01-01

    Barrett’s esophagus is a premalignant intermediate to esophageal adenocarcinoma, which develops in the context of chronic inflammation and exposure to bile and acid. We asked whether there might be common genomic alterations that could be identified as potential clinical biomarker(s) for Barrett’s esophagus by whole genome profiling. We detected copy number alterations and/or loss of heterozygosity (LOH) at fifty-six fragile sites in 20 patients with premalignant Barrett’s esophagus (BE). Chromosomal fragile sites are particularly sensitive to DNA breaks and have been shown to be frequent sites of rearrangement or loss in many human cancers. 78% of all genomic alterations detected by array-CGH were associated with fragile sites. Copy number losses in early BE were observed at particularly high frequency at FRA3B (81%), FRA9A/C (71.4%), FRA5E (52.4%) and FRA 4D (52.4%), and at lower frequencies in other fragile sites, including FRA1K (42.9%), FRAXC (42.9%), FRA 12B (33.3%) and FRA16D (33.3%). Due to the consistency of the region of copy number loss, we were able to verify these results by quantitative PCR which detected loss of FRA3B and FRA16D, in 83% and 40% of early molecular stage BE patients respectively. LOH in these cases was confirmed via pyrosequencing at FRA3B and FRA16D (75% and 70% respectively). Deletion and genomic instability at FRA3B and other fragile sites could thus be a biomarker of genetic damage in BE patients and a potential biomarker of cancer risk. PMID:20647332

  12. Deletion at fragile sites is a common and early event in Barrett's esophagus.

    PubMed

    Lai, Lisa A; Kostadinov, Rumen; Barrett, Michael T; Peiffer, Daniel A; Pokholok, Dimitry; Odze, Robert; Sanchez, Carissa A; Maley, Carlo C; Reid, Brian J; Gunderson, Kevin L; Rabinovitch, Peter S

    2010-08-01

    Barrett's esophagus (BE) is a premalignant intermediate to esophageal adenocarcinoma, which develops in the context of chronic inflammation and exposure to bile and acid. We asked whether there might be common genomic alterations that could be identified as potential clinical biomarker(s) for BE by whole genome profiling. We detected copy number alterations and/or loss of heterozygosity at 56 fragile sites in 20 patients with premalignant BE. Chromosomal fragile sites are particularly sensitive to DNA breaks and are frequent sites of rearrangement or loss in many human cancers. Seventy-eight percent of all genomic alterations detected by array-CGH were associated with fragile sites. Copy number losses in early BE were observed at particularly high frequency at FRA3B (81%), FRA9A/C (71.4%), FRA5E (52.4%), and FRA 4D (52.4%), and at lower frequencies in other fragile sites, including FRA1K (42.9%), FRAXC (42.9%), FRA 12B (33.3%), and FRA16D (33.3%). Due to the consistency of the region of copy number loss, we were able to verify these results by quantitative PCR, which detected the loss of FRA3B and FRA16D, in 83% and 40% of early molecular stage BE patients, respectively. Loss of heterozygosity in these cases was confirmed through pyrosequencing at FRA3B and FRA16D (75% and 70%, respectively). Deletion and genomic instability at FRA3B and other fragile sites could thus be a biomarker of genetic damage in BE patients and a potential biomarker of cancer risk. PMID:20647332

  13. Influence of common genetic variation on blood lipid levels, cardiovascular risk, and coronary events in two British prospective cohort studies

    PubMed Central

    Shah, Sonia; Casas, Juan P.; Gaunt, Tom R.; Cooper, Jackie; Drenos, Fotios; Zabaneh, Delilah; Swerdlow, Daniel I.; Shah, Tina; Sofat, Reecha; Palmen, Jutta; Kumari, Meena; Kivimaki, Mika; Ebrahim, Shah; Smith, George Davey; Lawlor, Debbie A.; Talmud, Philippa J.; Whittaker, John; Day, Ian N.M.; Hingorani, Aroon D.; Humphries, Steve E.

    2013-01-01

    Aims The aim of this study was to quantify the collective effect of common lipid-associated single nucleotide polymorphisms (SNPs) on blood lipid levels, cardiovascular risk, use of lipid-lowering medication, and risk of coronary heart disease (CHD) events. Methods and results Analysis was performed in two prospective cohorts: Whitehall II (WHII; N = 5059) and the British Women’s Heart and Health Study (BWHHS; N = 3414). For each participant, scores were calculated based on the cumulative effect of multiple genetic variants influencing total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). Compared with the bottom quintile, individuals in the top quintile of the LDL-C genetic score distribution had higher LDL-C {mean difference of 0.85 [95% confidence interval, (CI) = 0.76–0.94] and 0.63 [95% CI = 0.50–0.76] mmol/l in WHII and BWHHS, respectively}. They also tended to have greater odds of having ‘high-risk’ status (Framingham 10-year cardiovascular disease risk >20%) [WHII: odds ratio (OR) = 1.36 (0.93–1.98), BWHHS: OR = 1.49 (1.14–1.94)]; receiving lipid-lowering treatment [WHII: OR = 2.38 (1.57–3.59), BWHHS: OR = 2.24 (1.52–3.29)]; and CHD events [WHII: OR = 1.43 (1.02–2.00), BWHHS: OR = 1.31 (0.99–1.72)]. Similar associations were observed for the TC score in both studies. The TG score was associated with high-risk status and medication use in both studies. Neither HDL nor TG scores were associated with the risk of coronary events. The genetic scores did not improve discrimination over the Framingham risk score. Conclusion At the population level, common SNPs associated with LDL-C and TC contribute to blood lipid variation, cardiovascular risk, use of lipid-lowering medications and coronary events. However, their effects are too small to discriminate future lipid-lowering medication requirements or coronary events. PMID:22977227

  14. Cellular dynamical mechanisms for encoding the time and place of events along spatiotemporal trajectories in episodic memory

    PubMed Central

    Hasselmo, Michael E.; Giocomo, Lisa M.; Yoshida, Motoharu

    2010-01-01

    Understanding the mechanisms of episodic memory requires linking behavioural data and lesion effects to data on the dynamics of cellular membrane potentials and population interactions within these brain regions. Linking behavior to specific membrane channels and neurochemicals has implications for therapeutic applications. Lesions of the hippocampus, entorhinal cortex and subcortical nuclei impair episodic memory function in humans and animals, and unit recording data from these regions in behaving animals indicate episodic memory processes. Intracellular recording in these regions demonstrates specific cellular properties including resonance, membrane potential oscillations and bistable persistent spiking that could underlie the encoding and retrieval of episodic trajectories. A model presented here shows how intrinsic dynamical properties of neurons could mediate the encoding of episodic memories as complex spatiotemporal trajectories. The dynamics of neurons allow encoding and retrieval of unique episodic trajectories in multiple continuous dimensions including temporal intervals, personal location, the spatial coordinates and sensory features of perceived objects and generated actions, and associations between these elements. The model also addresses how cellular dynamics could underlie unit firing data suggesting mechanisms for coding continuous dimensions of space, time, sensation and action. PMID:20018213

  15. Adverse Events Lead to Drug Discontinuation More Commonly among Patients Who Receive Nafcillin than among Those Who Receive Oxacillin.

    PubMed

    Viehman, J Alexander; Oleksiuk, Louise-Marie; Sheridan, Kathleen R; Byers, Karin E; He, Peimei; Falcione, Bonnie A; Shields, Ryan K

    2016-05-01

    Nafcillin and oxacillin are used interchangeably in clinical practice, yet few studies have evaluated the safety of these two agents. Our objective was to compare the differential tolerabilities of nafcillin and oxacillin among hospitalized patients. We conducted a retrospective cohort study of all patients who received 12 g/day of nafcillin or oxacillin for at least 24 h. Two hundred twenty-four patients were included. Baseline characteristics and comorbidities were similar among patients receiving nafcillin (n = 160) and those receiving oxacillin (n = 64). Hypokalemia, defined as a potassium level of ≤3.3 mmol/liter or ≤2.9 mmol/liter or as a ≥0.5-mmol/liter decrease from the baseline level, occurred more frequently among patients who received nafcillin (51%, 20%, and 56%, respectively) than among those who received oxacillin (17%, 3%, and 34%, respectively; P < 0.0001, P = 0.0008, and P = 0.005, respectively). By multivariate logistic regression analysis, receipt of nafcillin was an independent predictor of severe hypokalemia (odds ratio [OR] = 6.74; 95% confidence interval [CI], 1.46 to 31.2; P = 0.02). Rates of hepatotoxicity did not differ between groups; however, acute kidney injury occurred more commonly with nafcillin than with oxacillin (18% versus 6%; P = 0.03). Overall, 18% of patients who received nafcillin discontinued therapy prematurely due to adverse events, compared to 2% of patients who received oxacillin (P = 0.0004). Nafcillin treatment is associated with higher rates of adverse events and treatment discontinuation than oxacillin among hospitalized adult patients. These findings have important implications for patients in both inpatient and outpatient settings, particularly patients who require long-term therapy and cannot be monitored routinely. Future randomized controlled studies evaluating the efficacy, costs, and tolerability of nafcillin versus oxacillin are warranted. PMID:26976858

  16. Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo

    PubMed Central

    Kagias, Konstantinos; Ahier, Arnaud; Fischer, Nadine; Jarriault, Sophie

    2012-01-01

    Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla. PMID:22493276

  17. Members of the NODE (Nanog and Oct4-associated deacetylase) complex and SOX-2 promote the initiation of a natural cellular reprogramming event in vivo.

    PubMed

    Kagias, Konstantinos; Ahier, Arnaud; Fischer, Nadine; Jarriault, Sophie

    2012-04-24

    Differentiated cells can be forced to change identity, either to directly adopt another differentiated identity or to revert to a pluripotent state. Direct reprogramming events can also occur naturally. We recently characterized such an event in Caenorhabditis elegans, in which a rectal cell switches to a neuronal cell. Here we have used this single-cell paradigm to investigate the molecular requirements of direct cell-type conversion, with a focus on the early steps. Our genetic analyses revealed the requirement of sem-4/Sall, egl-27/Mta, and ceh-6/Oct, members of the NODE complex recently identified in embryonic stem (ES) cells, and of the OCT4 partner sox-2, for the initiation of this natural direct reprogramming event. These four factors have been shown to individually impact on ES cell pluripotency; however, whether they act together to control cellular potential during development remained an open question. We further found that, in addition to acting at the same time, these factors physically associate, suggesting that they could act together as a NODE-like complex during this in vivo process. Finally, we have elucidated the functional domains in EGL-27/MTA that mediate its reprogramming activity in this system and have found that modulation of the posterior HOX protein EGL-5 is a downstream event to allow the initiation of Y identity change. Our data reveal unique in vivo functions in a natural direct reprogramming event for these genes that impact on ES cells pluripotency and suggest that conserved nuclear events could be shared between different cell plasticity phenomena across phyla. PMID:22493276

  18. Opossum carboxylesterases: sequences, phylogeny and evidence for CES gene duplication events predating the marsupial-eutherian common ancestor

    PubMed Central

    2008-01-01

    residues previously reported for human CES1 involved in catalysis, ligand binding, tertiary structure and organelle localization. Phylogenetic studies indicated the gene duplication events which generated ancestral mammalian CES genes predated the common ancestor for marsupial and eutherian mammals, and appear to coincide with the early diversification of tetrapods. PMID:18289373

  19. Loss of Inositol 1,4,5-Trisphosphate Receptors From Bile Duct Epithelia Is a Common Event in Cholestasis

    PubMed Central

    SHIBAO, KAZUNORI; HIRATA, KEIJI; ROBERT, MARIE E.; NATHANSON, MICHAEL H.

    2010-01-01

    Background & Aims: Cholestasis is one of the principal manifestations of liver disease and often results from disorders involving bile duct epithelia rather than hepatocytes. A range of disorders affects biliary epithelia, and no unifying pathophysiologic event in these cells has been identified as the cause of cholestasis. Here we examined the role of the inositol 1,4,5-trisphosphate receptor (InsP3R)/Ca2+ release channel in Ca2+ signaling and ductular secretion in animal models of cholestasis and in patients with cholestatic disorders. Methods: The expression and distribution of the InsP3R and related proteins were examined in rat cholangiocytes before and after bile duct ligation or treatment with endotoxin. Ca2+ signaling was examined in isolated bile ducts from these animals, whereas ductular bicarbonate secretion was examined in isolated perfused livers. Confocal immunofluorescence was used to examine cholangiocyte InsP3R expression in human liver biopsy specimens. Results: Expression of the InsP3R was selectively lost from biliary epithelia after bile duct ligation or endotoxin treatment. As a result, Ca2+ signaling and Ca2+-mediated bicarbonate secretion were lost as well, although other components of the Ca2+ signaling pathway and adenosine 3′,5′-cyclic monophosphate (cAMP)-mediated bicarbonate secretion both were preserved. Examination of human liver biopsy specimens showed that InsP3Rs also were lost from bile duct epithelia in a range of human cholestatic disorders, although InsP3R expression was intact in noncholestatic liver disease. Conclusions: InsP3-mediated Ca2+ signaling in bile duct epithelia appears to be important for normal bile secretion in the liver, and loss of InsP3Rs may be a final common pathway for cholestasis. PMID:14517800

  20. Clonal Analysis in Recurrent Astrocytic, Oligoastrocytic and Oligodendroglial Tumors Implicates IDH1- Mutation as Common Tumor Initiating Event

    PubMed Central

    von Eckardstein, Kajetan; Kiwit, Jürgen; Stockhammer, Florian; Horaczek, Jörn A.; Veelken, Julian; Herold-Mende, Christel; Jeuken, Judith; von Deimling, Andreas; Mueller, Wolf

    2012-01-01

    Background To investigate the dynamics of inter- and intratumoral molecular alterations during tumor progression in recurrent gliomas. Methodology/Principal Findings To address intertumoral heterogeneity we investigated non- microdissected tumor tissue of 106 gliomas representing 51 recurrent tumors. To address intratumoral heterogeneity a set of 16 gliomas representing 7 tumor pairs with at least one recurrence, and 4 single mixed gliomas were investigated by microdissection of distinct oligodendroglial and astrocytic tumor components. All tumors and tumor components were analyzed for allelic loss of 1p/19q (LOH 1p/19q), for TP53- mutations and for R132 mutations in the IDH1 gene. The investigation of non- microdissected tumor tissue revealed clonality in 75% (38/51). Aberrant molecular alterations upon recurrence were detected in 25% (13/51). 64% (9/14) of these were novel and associated with tumor progression. Loss of previously detected alterations was observed in 36% (5/14). One tumor pair (1/14; 7%) was significant for both. Intratumoral clonality was detected in 57% (4/7) of the microdissected tumor pairs and in 75% (3/4) of single microdissected tumors. 43% (3/7) of tumor pairs and one single tumor (25%) revealed intratumoral heterogeneity. While intratumoral heterogeneity affected both the TP53- mutational status and the LOH1p/19q status, all tumors with intratumoral heterogeneity shared the R132 IDH1- mutation as a common feature in both their microdissected components. Conclusions/Significance The majority of recurrent gliomas are of monoclonal origin. However, the detection of divertive tumor cell clones in morphological distinct tumor components sharing IDH1- mutations as early event may provide insight into the tumorigenesis of true mixed gliomas. PMID:22844452

  1. Cellular basis of Alzheimer's disease.

    PubMed

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-12-01

    Alzheimer's disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD. PMID:21369424

  2. The effects of okra (Abelmoschus esculentus Linn.) on the cellular events associated with Alzheimer's disease in a stably expressed HFE neuroblastoma SH-SY5Y cell line.

    PubMed

    Mairuae, Nootchanat; Connor, James R; Lee, Sang Y; Cheepsunthorn, Poonlarp; Tongjaroenbuangam, Walaiporn

    2015-08-31

    It has been reported that persons carrying the H63D variant in their hemochromatosis (HFE) gene are at increased risk of Alzheimer's disease (AD). We investigated the possibility that okra (Abelmoschus esculentus) and quercetin could mitigate this risk factor by examining its effect on AD-associated cellular events in HFE stably expressing SH-SY5Y cells. Treatment of H63D HFE cells either with okra or quercetin significantly decreased reactive oxygen species (ROS), hydrogen peroxide (H2O2), and protein oxidation compared to untreated cells. The levels of tau phosphorylation at serine-199, serine-202, and serine-396 sites were also significantly decreased when cells were treated with okra. Exposure of the H63D and wild type (WT) cells to iron increased tau phosphorylation, but this response was decreased significantly when cells were treated with okra. The mechanism responsible for these changes appears to be related to decreased glycogen synthase kinase (GSK)-3β activity, an upstream signaling kinase of tau phosphorylation. We also established that okra treatment dramatically decreases intracellular iron levels in H63D cells compared to untreated cells. Our results provide important in vitro data on the effects of okra on various AD-associated cellular processes in H63D variant HFE cells. These results suggest okra may be beneficial in people expressing the H63D variant to reduce the risk of AD and other neurodegenerative diseases related to oxidative stress. Further in vivo studies would help confirm this. PMID:26170247

  3. Common Cold

    MedlinePlus

    ... News & Events Volunteer NIAID > Health & Research Topics > Common Cold Skip Website Tools Website Tools Print this page ... Help people who are suffering from the common cold by volunteering for NIAID clinical studies on ClinicalTrials. ...

  4. Development of an event-specific hydrolysis probe quantitative real-time polymerase chain reaction assay for Embrapa 5.1 genetically modified common bean (Phaseolus vulgaris).

    PubMed

    Treml, Diana; Venturelli, Gustavo L; Brod, Fábio C A; Faria, Josias C; Arisi, Ana C M

    2014-12-10

    A genetically modified (GM) common bean event, namely Embrapa 5.1, resistant to the bean golden mosaic virus (BGMV), was approved for commercialization in Brazil. Brazilian regulation for genetically modified organism (GMO) labeling requires that any food containing more than 1% GMO be labeled. The event-specific polymerase chain reaction (PCR) method has been the primary trend for GMO identification and quantitation because of its high specificity based on the flanking sequence. This work reports the development of an event-specific assay, named FGM, for Embrapa 5.1 detection and quantitation by use of SYBR Green or hydrolysis probe. The FGM assay specificity was tested for Embrapa 2.3 event (a noncommercial GM common bean also resistant to BGMV), 46 non-GM common bean varieties, and other crop species including maize, GM maize, soybean, and GM soybean. The FGM assay showed high specificity to detect the Embrapa 5.1 event. Standard curves for the FGM assay presented a mean efficiency of 95% and a limit of detection (LOD) of 100 genome copies in the presence of background DNA. The primers and probe developed are suitable for the detection and quantitation of Embrapa 5.1. PMID:25437743

  5. Common and Segregated Neural Substrates for Automatic Conceptual and Affective Priming as Revealed by Event-Related Functional Magnetic Resonance Imaging

    ERIC Educational Resources Information Center

    Liu, Hongyan; Hu, Zhiguo; Peng, Danling; Yang, Yanhui; Li, Kuncheng

    2010-01-01

    The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming…

  6. Evidence for a Common Acceleration Mechanism for Enrichments of 3He and Heavy Ions in Impulsive SEP Events

    NASA Astrophysics Data System (ADS)

    Mason, Glenn M.; Nitta, Nariaki V.; Wiedenbeck, Mark E.; Innes, Davina E.

    2016-06-01

    We have surveyed the period 1997–2015 for a rare type of 3He-rich solar energetic particle (SEP) event, with enormously enhanced values of the S/O ratio, that differs from the majority of 3He-rich events, which show enhancements of heavy ions increasing smoothly with mass. Sixteen events were found, most of them small but with solar source characteristics similar to other 3He-rich SEP events. A single event on 2014 May 16 had higher intensities than the others, and curved Si and S spectra that crossed the O spectrum above ∼200 keV nucleon‑1. Such crossings of heavy-ion spectra have never previously been reported. The dual enhancement of Si and S suggests that element Q/M ratio is critical to the enhancement since this pair of elements uniquely has very similar Q/M ratios over a wide range of temperatures. Besides 3He, Si, and S, in this same event the C, N, and Fe spectra also showed curved shape and enhanced abundances compared to O. The spectral similarities suggest that all have been produced from the same mechanism that enhances 3He. The enhancements are large only in the high-energy portion of the spectrum, and so affect only a small fraction of the ions. The observations suggest that the accelerated plasma was initially cool (∼0.4 MK) and was then heated to a few million kelvin to generate the preferred Q/M ratio in the range C–Fe. The temperature profile may be the distinct feature of these events that produces the unusual abundance signature.

  7. Common Neural Systems Associated with the Recognition of Famous Faces and Names: An Event-Related fMRI Study

    ERIC Educational Resources Information Center

    Nielson, Kristy A.; Seidenberg, Michael; Woodard, John L.; Durgerian, Sally; Zhang, Qi; Gross, William L.; Gander, Amelia; Guidotti, Leslie M.; Antuono, Piero; Rao, Stephen M.

    2010-01-01

    Person recognition can be accomplished through several modalities (face, name, voice). Lesion, neurophysiology and neuroimaging studies have been conducted in an attempt to determine the similarities and differences in the neural networks associated with person identity via different modality inputs. The current study used event-related…

  8. Histological characterization and quantification of cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue.

    PubMed

    Praet, Jelle; Santermans, Eva; Reekmans, Kristien; de Vocht, Nathalie; Le Blon, Debbie; Hoornaert, Chloé; Daans, Jasmijn; Goossens, Herman; Berneman, Zwi; Hens, Niel; Van der Linden, Annemie; Ponsaerts, Peter

    2014-01-01

    Preclinical animal studies involving intracerebral (stem) cell grafting are gaining popularity in many laboratories due to the reported beneficial effects of cell grafting on various diseases or traumata of the central nervous system (CNS). In this chapter, we describe a histological workflow to characterize and quantify cellular events following neural and fibroblast(-like) stem cell grafting in healthy and demyelinated CNS tissue. First, we provide standardized protocols to isolate and culture eGFP(+) neural and fibroblast(-like) stem cells from embryonic mouse tissue. Second, we describe flow cytometric procedures to determine cell viability, eGFP transgene expression, and the expression of different stem cell lineage markers. Third, we explain how to induce reproducible demyelination in the CNS of mice by means of cuprizone administration, a validated mouse model for human multiple sclerosis. Fourth, the technical procedures for cell grafting in the CNS are explained in detail. Finally, an optimized and validated workflow for the quantitative histological analysis of cell graft survival and endogenous astroglial and microglial responses is provided. PMID:25173390

  9. The principal PINK1 and Parkin cellular events triggered in response to dissipation of mitochondrial membrane potential occur in primary neurons

    PubMed Central

    Koyano, Fumika; Okatsu, Kei; Ishigaki, Shinsuke; Fujioka, Yusuke; Kimura, Mayumi; Sobue, Gen; Tanaka, Keiji; Matsuda, Noriyuki

    2013-01-01

    PINK1 and PARKIN are causal genes for hereditary Parkinsonism. Recent studies have shown that PINK1 and Parkin play a pivotal role in the quality control of mitochondria, and dysfunction of either protein likely results in the accumulation of low-quality mitochondria that triggers early-onset familial Parkinsonism. As neurons are destined to degenerate in PINK1/Parkin-associated Parkinsonism, it is imperative to investigate the function of PINK1 and Parkin in neurons. However, most studies investigating PINK1/Parkin have used non-neuronal cell lines. Here we show that the principal PINK1 and Parkin cellular events that have been documented in non-neuronal lines in response to mitochondrial damage also occur in primary neurons. We found that dissipation of the mitochondrial membrane potential triggers phosphorylation of both PINK1 and Parkin and that, in response, Parkin translocates to depolarized mitochondria. Furthermore, Parkin's E3 activity is re-established concomitant with ubiquitin–ester formation at Cys431 of Parkin. As a result, mitochondrial substrates in neurons become ubiquitylated. These results underscore the relevance of the PINK1/Parkin-mediated mitochondrial quality control pathway in primary neurons and shed further light on the underlying mechanisms of the PINK1 and Parkin pathogenic mutations that predispose Parkinsonism in vivo. PMID:23751051

  10. A common mineralocorticoid receptor polymorphism (I180V) interacts with life events in relation to perfectionism in eating disorders: a pilot study.

    PubMed

    Slof-Op't Landt, Margarita C T; DeRijk, Roel H; van Son, Gabrielle E; Suchiman, H Eka D; Meulenbelt, Ingrid; Slagboom, P Eline; Van Furth, Eric F

    2014-11-01

    The stress response is regulated by the mineralocorticoid receptor (MR) and the glucocorticoid receptor (GR). When the balance between GR and MR signalling is disturbed, one's capacity to cope with a stressful event is diminished. In this pilot study, we tested the hypothesis that an interaction between common variants in the MR (rs5522) or GR gene (rs41423247) and stressful life events influences perfectionism levels in a group of patients with an eating disorder (ED; n = 113). Patients carrying the minor G allele of rs5522 had a higher perfectionism score if more stressful life events were experienced [β = 0.95, t(109) = 3.75, p < 0.01]. This effect was not found for patients carrying the AA genotype. These results suggest that rs5522 G allele carriers might be vulnerable to stressful life events. When patients with an ED are carriers and experience multiple life events, this might fuel their insecurity, which in turn may engender higher levels of perfectionism. Further studies are necessary to replicate and expand our findings. PMID:25220664

  11. Analysis of the Sam50 translocase of Excavate organisms supports evolution of divergent organelles from a common endosymbiotic event

    PubMed Central

    Kay, Christopher J.; Lawler, Karen; Kerr, Ian D.

    2013-01-01

    As free-living organisms the ancestors of mitochondria and plastids encoded complete genomes, proteomes and metabolomes. As these symbionts became organelles all these aspects were reduced – genomes have degenerated with the host nucleus now encoding the most of the remaining endosymbiont proteome, while the metabolic processes of the symbiont have been streamlined to the functions of the emerging organelle. By contrast, the topology of the endosymbiont membrane has been preserved, necessitating the development of complex pathways for membrane insertion and translocation. In this study, we examine the characteristics of the endosymbiont-derived β-barrel insertase Sam501 in the excavate super-group. A candidate is further characterized in Trichomonas vaginalis, an unusual eukaryote possessing degenerate hydrogen-producing mitochondria called hydrogenosomes. This information supports a mitochondriate eukaryotic common ancestor with a similarly evolved β-barrel insertase, which has continued to be conserved in degenerate mitochondria. PMID:24147756

  12. Weight Loss and Decrease of Body Mass Index during Allogeneic Stem Cell Transplantation Are Common Events with Limited Clinical Impact

    PubMed Central

    Rieger, Christina T.; Wischumerski, Isabel; Rust, Christian; Fiegl, Michael

    2015-01-01

    Purpose Weight loss in cancer patients has been attributed with significant morbidity and mortality. During allogeneic stem cell transplantation (SCT), oral nutrition is often hampered and hence total parenteral nutrition (TPN) is necessary. We therefore investigated the course of weight during stem cell transplantation and the clinical consequences of weight change. Methods 180 consecutive patients who received allogeneic SCT between January 2010 and December 2011 at our center were analyzed for weight loss, laboratory and clinical parameters. Results During SCT, a median decrease of 6.6% of body mass index (BMI) was observed for the whole population (from 25.3 at admission to 23.6 at discharge), and a 1.6fold increase of malnutrition despite use of TPN (28.3% to 45.0%). 55.6% of patients experienced a significant weight loss of ≥5% with a median decrease of 9.2% in BMI. Serum levels of albumin, total protein and cholesterol rapidly decreased during conditioning therapy. After a median of 2.4 years, the median BMI was still only 23.4 (not different from discharge). However, we did not observe a meaningful difference in side effects and survival between patients that did or did not lose weight. Conclusion Weight loss is commonly observed during allogeneic SCT despite TPN, but the clinical consequences thereof seem limited: we observed no significant impact on patients with a decrease ≥ 5% in BMI on transplant outcome, side effects or survival. PMID:26683031

  13. Proton-dependent coniferin transport, a common major transport event in differentiating xylem tissue of woody plants.

    PubMed

    Tsuyama, Taku; Kawai, Ryo; Shitan, Nobukazu; Matoh, Toru; Sugiyama, Junji; Yoshinaga, Arata; Takabe, Keiji; Fujita, Minoru; Yazaki, Kazufumi

    2013-06-01

    Lignin biosynthesis is an essential physiological activity of vascular plants if they are to survive under various environmental stresses on land. The biosynthesis of lignin proceeds in the cell wall by polymerization of precursors; the initial step of lignin polymerization is the transportation of lignin monomers from the cytosol to the cell wall, which is critical for lignin formation. There has been much debate on the transported form of the lignin precursor, either as free monolignols or their glucosides. In this study, we performed biochemical analyses to characterize the membrane transport mechanism of lignin precursors using angiosperms, hybrid poplar (Populus sieboldii × Populus grandidentata) and poplar (Populus sieboldii), as well gymnosperms, Japanese cypress (Chamaecyparis obtusa) and pine (Pinus densiflora). Membrane vesicles prepared from differentiating xylem tissues showed clear ATP-dependent transport activity of coniferin, whereas less than 4% of the coniferin transport activity was seen for coniferyl alcohol. Bafilomycin A1 and proton gradient erasers markedly inhibited coniferin transport in hybrid poplar membrane vesicles; in contrast, vanadate had no effect. Cis-inhibition experiments suggested that this transport activity was specific for coniferin. Membrane fractionation of hybrid poplar microsomes demonstrated that transport activity was localized to the tonoplast- and endomembrane-rich fraction. Differentiating xylem of Japanese cypress exhibited almost identical transport properties, suggesting the involvement of a common endomembrane-associated proton/coniferin antiport mechanism in the lignifying tissues of woody plants, both angiosperms and gymnosperms. PMID:23585651

  14. Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event

    PubMed Central

    Oshida, Keiyu; Vasani, Naresh; Waxman, David J.; Corton, J. Christopher

    2016-01-01

    Signal transducer and activator of transcription 5b (STAT5b) is a growth hormone (GH)-activated transcription factor and a master regulator of sexually dimorphic gene expression in the liver. Disruption of the GH hypothalamo-pituitary-liver axis controlling STAT5b activation can lead to metabolic dysregulation, steatosis, and liver cancer. Computational approaches were developed to identify factors that disrupt STAT5b function in a mouse liver gene expression compendium. A biomarker comprised of 144 STAT5b-dependent genes was derived using comparisons between wild-type male and wild-type female mice and between STAT5b-null and wild-type mice. Correlations between the STAT5b biomarker gene set and a test set comprised of expression datasets (biosets) with known effects on STAT5b function were evaluated using a rank-based test (the Running Fisher algorithm). Using a similarity p-value ≤ 10−4, the test achieved a balanced accuracy of 99% and 97% for detection of STAT5b activation or STAT5b suppression, respectively. The STAT5b biomarker gene set was then used to identify factors that activate (masculinize) or suppress (feminize) STAT5b function in an annotated mouse liver and primary hepatocyte gene expression compendium of ~1,850 datasets. Disruption of GH-regulated STAT5b is a common phenomenon in liver in vivo, with 5% and 29% of the male datasets, and 11% and 13% of the female datasets, associated with masculinization or feminization, respectively. As expected, liver STAT5b activation/masculinization occurred at puberty and suppression/feminization occurred during aging and in mutant mice with defects in GH signaling. A total of 70 genes were identified that have effects on STAT5b activation in genetic models in which the gene was inactivated or overexpressed. Other factors that affected liver STAT5b function were shown to include fasting, caloric restriction and infections. Together, these findings identify diverse factors that perturb the hypothalamo

  15. Disruption of STAT5b-Regulated Sexual Dimorphism of the Liver Transcriptome by Diverse Factors Is a Common Event.

    PubMed

    Oshida, Keiyu; Vasani, Naresh; Waxman, David J; Corton, J Christopher

    2016-01-01

    Signal transducer and activator of transcription 5b (STAT5b) is a growth hormone (GH)-activated transcription factor and a master regulator of sexually dimorphic gene expression in the liver. Disruption of the GH hypothalamo-pituitary-liver axis controlling STAT5b activation can lead to metabolic dysregulation, steatosis, and liver cancer. Computational approaches were developed to identify factors that disrupt STAT5b function in a mouse liver gene expression compendium. A biomarker comprised of 144 STAT5b-dependent genes was derived using comparisons between wild-type male and wild-type female mice and between STAT5b-null and wild-type mice. Correlations between the STAT5b biomarker gene set and a test set comprised of expression datasets (biosets) with known effects on STAT5b function were evaluated using a rank-based test (the Running Fisher algorithm). Using a similarity p-value ≤ 10(-4), the test achieved a balanced accuracy of 99% and 97% for detection of STAT5b activation or STAT5b suppression, respectively. The STAT5b biomarker gene set was then used to identify factors that activate (masculinize) or suppress (feminize) STAT5b function in an annotated mouse liver and primary hepatocyte gene expression compendium of ~1,850 datasets. Disruption of GH-regulated STAT5b is a common phenomenon in liver in vivo, with 5% and 29% of the male datasets, and 11% and 13% of the female datasets, associated with masculinization or feminization, respectively. As expected, liver STAT5b activation/masculinization occurred at puberty and suppression/feminization occurred during aging and in mutant mice with defects in GH signaling. A total of 70 genes were identified that have effects on STAT5b activation in genetic models in which the gene was inactivated or overexpressed. Other factors that affected liver STAT5b function were shown to include fasting, caloric restriction and infections. Together, these findings identify diverse factors that perturb the hypothalamo

  16. Algorithm for Screening Phasor Measurement Unit Data for Power System Events and Categories and Common Characteristics for Events Seen in Phasor Measurement Unit Relative Phase-Angle Differences and Frequency Signals

    SciTech Connect

    Allen, A.; Santoso, S.; Muljadi, E.

    2013-08-01

    A network of multiple phasor measurement units (PMU) was created, set up, and maintained at the University of Texas at Austin to obtain actual power system measurements for power system analysis. Power system analysis in this report covers a variety of time ranges, such as short- term analysis for power system disturbances and their effects on power system behavior and long- term power system behavior using modal analysis. The first objective of this report is to screen the PMU data for events. The second objective of the report is to identify and describe common characteristics extracted from power system events as measured by PMUs. The numerical characteristics for each category and how these characteristics are used to create selection rules for the algorithm are also described. Trends in PMU data related to different levels and fluctuations in wind power output are also examined.

  17. Cellular basis of Alzheimer’s disease

    PubMed Central

    Bali, Jitin; Halima, Saoussen Ben; Felmy, Boas; Goodger, Zoe; Zurbriggen, Sebastian; Rajendran, Lawrence

    2010-01-01

    Alzheimer’s disease (AD) is the most common form of neurodegenerative disease. A characteristic feature of the disease is the presence of amyloid-β (Aβ) which either in its soluble oligomeric form or in the plaque-associated form is causally linked to neurodegeneration. Aβ peptide is liberated from the membrane-spanning -amyloid precursor protein by sequential proteolytic processing employing β- and γ-secretases. All these proteins involved in the production of Aβ peptide are membrane associated and hence, membrane trafficking and cellular compartmentalization play important roles. In this review, we summarize the key cellular events that lead to the progression of AD. PMID:21369424

  18. Pain Flare Is a Common Adverse Event in Steroid-Naïve Patients After Spine Stereotactic Body Radiation Therapy: A Prospective Clinical Trial

    SciTech Connect

    Chiang, Andrew; Zeng, Liang; Zhang, Liying; Lochray, Fiona; Korol, Renee; Loblaw, Andrew; Chow, Edward; Sahgal, Arjun

    2013-07-15

    Purpose: To determine the incidence of pain flare after spine stereotactic body radiation therapy (SBRT) in steroid-naïve patients and identify predictive factors. Methods and Materials: Forty-one patients were treated with spine SBRT between February 2010 and April 2012. All patients had their pain assessed at baseline, during, and for 10 days after SBRT using the Brief Pain Inventory. All pain medications were recorded daily and narcotics converted to an oral morphine equivalent dose. Pain flare was defined as a 2-point increase in worst pain score as compared with baseline with no decrease in analgesic intake, a 25% increase in analgesic intake as compared with baseline with no decrease in worst pain score, or if corticosteroids were initiated at any point during or after SBRT because of pain. Results: The median age and Karnofsky performance status were 57.5 years (range, 27-80 years) and 80 (range, 50-100), respectively. Eighteen patients were treated with 20-24 Gy in a single fraction, whereas 23 patients were treated with 24-35 Gy in 2-5 fractions. Pain flare was observed in 68.3% of patients (28 of 41), most commonly on day 1 after SBRT (29%, 8 of 28). Multivariate analysis identified a higher Karnofsky performance status (P=.02) and cervical (P=.049) or lumbar (P=.02) locations as significant predictors of pain flare. In those rescued with dexamethasone, a significant decrease in pain scores over time was subsequently observed (P<.0001). Conclusions: Pain flare is a common adverse event after spine SBRT and occurs most commonly the day after treatment completion. Patients should be appropriately consented for this adverse event.

  19. Comprehensive analysis of RET common and rare variants in a series of Spanish Hirschsprung patients confirms a synergistic effect of both kinds of events

    PubMed Central

    2011-01-01

    Background RET is the major gene associated to Hirschsprung disease (HSCR) with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. In the present study, we have performed a comprehensive study of our HSCR series evaluating the involvement of both RET rare variants (RVs) and common variants (CVs) in the context of the disease. Methods RET mutational screening was performed by dHPLC and direct sequencing for the identification of RVs. In addition Taqman technology was applied for the genotyping of 3 RET CVs previously associated to HSCR, including a variant lying in an enhancer domain within RET intron 1 (rs2435357). Statistical analyses were performed using the SPSS v.17.0 to analyze the distribution of the variants. Results Our results confirm the strongest association to HSCR for the "enhancer" variant, and demonstrate a significantly higher impact of it in male versus female patients. Integration of the RET RVs and CVs analysis showed that in 91.66% of cases with both kinds of mutational events, the enhancer allele is in trans with the allele bearing the RET RV. Conclusions A gender effect exists on both the transmission and distribution of rare coding and common HSCR causing mutations. In addition, these RET CVs and RVs seem to act in a synergistic way leading to HSCR phenotype. PMID:21995290

  20. Common Phenolic Metabolites of Flavonoids, but Not Their Unmetabolized Precursors, Reduce the Secretion of Vascular Cellular Adhesion Molecules by Human Endothelial Cells123

    PubMed Central

    Warner, Emily F; Zhang, Qingzhi; Raheem, K Saki; O’Hagan, David; O’Connell, Maria A; Kay, Colin D

    2016-01-01

    Background: Flavonoids have been implicated in the prevention of cardiovascular disease; however, their mechanisms of action have yet to be elucidated, possibly because most previous in vitro studies have used supraphysiological concentrations of unmetabolized flavonoids, overlooking their more bioavailable phenolic metabolites. Objective: We aimed to explore the effects of phenolic metabolites and their precursor flavonoids at physiologically achievable concentrations, in isolation and combination, on soluble vascular cellular adhesion molecule-1 (sVCAM-1). Method: Fourteen phenolic acid metabolites and 6 flavonoids were screened at 1 μM for their relative effects on sVCAM-1 secretion by human umbilical vein endothelial cells stimulated with tumor necrosis factor alpha (TNF-α). The active metabolites were further studied for their response at different concentrations (0.01 μM–100 μM), structure-activity relationships, and effect on vascular cellular adhesion molecule (VCAM)-1 mRNA expression. In addition, the additive activity of the metabolites and flavonoids was investigated by screening 25 unique mixtures at cumulative equimolar concentrations of 1 μM. Results: Of the 20 compounds screened at 1 μM, inhibition of sVCAM-1 secretion was elicited by 4 phenolic metabolites, of which protocatechuic acid (PCA) was the most active (−17.2%, P = 0.05). Investigations into their responses at different concentrations showed that PCA significantly reduced sVCAM-1 15.2–36.5% between 1 and 100 μM, protocatechuic acid-3-sulfate and isovanillic acid reduced sVCAM-1 levels 12.2–54.7% between 10 and 100 μM, and protocatechuic acid-4-sulfate and isovanillic acid-3-glucuronide reduced sVCAM-1 secretion 27.6% and 42.8%, respectively, only at 100 μM. PCA demonstrated the strongest protein response and was therefore explored for its effect on VCAM-1 mRNA, where 78.4% inhibition was observed only after treatment with 100 μM PCA. Mixtures of the metabolites showed no

  1. Stakeholder perspectives on implementing the National Cancer Institute's patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Bruner, Deborah Watkins; Hanisch, Laura J; Reeve, Bryce B; Trotti, Andy M; Schrag, Deborah; Sit, Laura; Mendoza, Tito R; Minasian, Lori; O'Mara, Ann; Denicoff, Andrea M; Rowland, Julia H; Montello, Michael; Geoghegan, Cindy; Abernethy, Amy P; Clauser, Steven B; Castro, Kathleen; Mitchell, Sandra A; Burke, Laurie; Trentacosti, Ann Marie; Basch, Ethan M

    2011-03-01

    The National Cancer Institute (NCI) is developing a patient-reported version of its Common Terminology Criteria for Adverse Events, called the "PRO-CTCAE." The PRO-CTCAE consists of a library of patient-reported items which can be administered in clinical trials to directly capture the patient experience of adverse events during cancer treatment, as well as a software platform for administering these items via computer or telephone. In order to better understand the impressions of stakeholders involved in cancer clinical research about the potential value of the PRO-CTCAE approach to capturing adverse event information in clinical research, as well as their perspectives about barriers and strategies for implementing the PRO-CTCAE in NCI-sponsored cancer trials, a survey was conducted. A survey including structured and open-ended questions was developed to elicit perceptions about the use of patient-reported outcomes (PROs) for adverse event reporting, and to explore logistical considerations for implementing the PRO-CTCAE in cancer trials. The survey was distributed electronically and by paper to a convenience sample of leadership and committee members in the NCI's cooperative group network, including principal investigators, clinical investigators, research nurses, data managers, patient advocates, and representatives of the NCI and Food and Drug Administration. Between October, 2008 through February, 2009, 727 surveys were collected. Most respondents (93%) agreed that patient reporting of adverse symptoms would be useful for improving understanding of the patient experience with treatment in cancer trials, and 88%, 80%, and 76%, respectively, endorsed that administration of PRO-CTCAE items in clinical trials would improve the completeness, accuracy, and efficiency of symptom data collection. More than three fourths believed that patient reports would be useful for informing treatment dose modifications and towards FDA regulatory evaluation of drugs. Eighty

  2. Development of the National Cancer Institute's patient-reported outcomes version of the common terminology criteria for adverse events (PRO-CTCAE).

    PubMed

    Basch, Ethan; Reeve, Bryce B; Mitchell, Sandra A; Clauser, Steven B; Minasian, Lori M; Dueck, Amylou C; Mendoza, Tito R; Hay, Jennifer; Atkinson, Thomas M; Abernethy, Amy P; Bruner, Deborah W; Cleeland, Charles S; Sloan, Jeff A; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St Germain, Diane; O'Mara, Ann M; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B; Schrag, Deborah

    2014-09-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute's (NCI's) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  3. Development of the National Cancer Institute’s Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Reeve, Bryce B.; Mitchell, Sandra A.; Clauser, Steven B.; Minasian, Lori M.; Dueck, Amylou C.; Mendoza, Tito R.; Hay, Jennifer; Atkinson, Thomas M.; Abernethy, Amy P.; Bruner, Deborah W.; Cleeland, Charles S.; Sloan, Jeff A.; Chilukuri, Ram; Baumgartner, Paul; Denicoff, Andrea; St. Germain, Diane; O’Mara, Ann M.; Chen, Alice; Kelaghan, Joseph; Bennett, Antonia V.; Sit, Laura; Rogak, Lauren; Barz, Allison; Paul, Diane B.; Schrag, Deborah

    2014-01-01

    The standard approach for documenting symptomatic adverse events (AEs) in cancer clinical trials involves investigator reporting using the National Cancer Institute’s (NCI’s) Common Terminology Criteria for Adverse Events (CTCAE). Because this approach underdetects symptomatic AEs, the NCI issued two contracts to create a patient-reported outcome (PRO) measurement system as a companion to the CTCAE, called the PRO-CTCAE. This Commentary describes development of the PRO-CTCAE by a group of multidisciplinary investigators and patient representatives and provides an overview of qualitative and quantitative studies of its measurement properties. A systematic evaluation of all 790 AEs listed in the CTCAE identified 78 appropriate for patient self-reporting. For each of these, a PRO-CTCAE plain language term in English and one to three items characterizing the frequency, severity, and/or activity interference of the AE were created, rendering a library of 124 PRO-CTCAE items. These items were refined in a cognitive interviewing study among patients on active cancer treatment with diverse educational, racial, and geographic backgrounds. Favorable measurement properties of the items, including construct validity, reliability, responsiveness, and between-mode equivalence, were determined prospectively in a demographically diverse population of patients receiving treatments for many different tumor types. A software platform was built to administer PRO-CTCAE items to clinical trial participants via the internet or telephone interactive voice response and was refined through usability testing. Work is ongoing to translate the PRO-CTCAE into multiple languages and to determine the optimal approach for integrating the PRO-CTCAE into clinical trial workflow and AE analyses. It is envisioned that the PRO-CTCAE will enhance the precision and patient-centeredness of adverse event reporting in cancer clinical research. PMID:25265940

  4. Patient-Reported Outcomes in Cancer Clinical Trials: Measuring Symptomatic Adverse Events With the National Cancer Institute's Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE).

    PubMed

    Kluetz, Paul G; Chingos, Diana T; Basch, Ethan M; Mitchell, Sandra A

    2016-01-01

    Systematic capture of the patient perspective can inform the development of new cancer therapies. Patient-reported outcomes (PROs) are commonly included in cancer clinical trials; however, there is heterogeneity in the constructs, measures, and analytic approaches that have been used making these endpoints challenging to interpret. There is renewed effort to identify rigorous methods to obtain high-quality and informative PRO data from cancer clinical trials. In this setting, PROs are used to address specific research objectives, and an important objective that spans the product development life cycle is the assessment of safety and tolerability. The U.S. Food and Drug Administration's (FDA) Office of Hematology and Oncology Products (OHOP) has identified symptomatic adverse events (AEs) as a central PRO concept, and a systematic assessment of patient-reported symptomatic AEs can provide data to complement clinician reporting. The National Cancer Institute's Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is being evaluated by multiple stakeholders, including the FDA, and is considered a promising tool to provide a standard yet flexible method to assess symptomatic AEs from the patient perspective. In this article, we briefly review the FDA OHOP's perspective on PROs in cancer trials submitted to the FDA and focus on the assessment of symptomatic AEs using PRO-CTCAE. We conclude by discussing further work that must be done to broaden the use of PRO-CTCAE as a method to provide patient-centered data that can complement existing safety and tolerability assessments across cancer clinical trials. PMID:27249687

  5. Collective specification of cellular development.

    PubMed

    Sachs, Tsvi

    2003-09-01

    Studies of chimeras and in vivo development demonstrate that cell lineages are often quite variable, apparently in response to chance perturbations. This points to an apparent contradiction: although individual cells are the units of genetic information and differentiation, not all cellular events need be precise for the development of functional organisms. The social organization of ants can serve as a metaphor that helps understand the mechanisms that underlie such development. Ants suggest that continued cellular interactions and environmental conditions could specify the proportion and general location of specialized units. Leaf venation is used as a concrete example of this general principle. A signal produced continuously by all cells specifies a requirement for vein differentiation. The cells that respond by differentiation then transport the signal away from the leaf; this removal acting as a feedback indicating that the requirement is being met. Because transport increases during vein differentiation, early initiation occurs in excess and vein 'competition' for the signal assures an acceptable outcome. Such specification would be robust since it does not depend on events in any single cell, and chance events, rather than being corrected or reversed, may be built upon in reaching an expected, collective phenotype. The absence of detailed information preceding development distinguishes this hypothesis from the common alternatives of a program or blueprint. Collective specification would have important implications for developmental plasticity and evolution. PMID:12938179

  6. Decreasing electron flux through the cytochrome and/or alternative respiratory pathways triggers common and distinct cellular responses dependent on growth conditions.

    PubMed

    Kühn, Kristina; Yin, Guangkun; Duncan, Owen; Law, Simon R; Kubiszewski-Jakubiak, Szymon; Kaur, Parwinder; Meyer, Etienne; Wang, Yan; Small, Catherine Colas des Francs; Giraud, Estelle; Narsai, Reena; Whelan, James

    2015-01-01

    Diverse signaling pathways are activated by perturbation of mitochondrial function under different growth conditions.Mitochondria have emerged as an important organelle for sensing and coping with stress in addition to being the sites of important metabolic pathways. Here, responses to moderate light and drought stress were examined in different Arabidopsis (Arabidopsis thaliana) mutant plants lacking a functional alternative oxidase (alternative oxidase1a [aox1a]), those with reduced cytochrome electron transport chain capacity (T3/T7 bacteriophage-type RNA polymerase, mitochondrial, and plastidial [rpoTmp]), and double mutants impaired in both pathways (aox1a:rpoTmp). Under conditions considered optimal for growth, transcriptomes of aox1a and rpoTmp were distinct. Under adverse growth conditions, however, transcriptome changes in aox1a and rpoTmp displayed a highly significant overlap and were indicative of a common mitochondrial stress response and down-regulation of photosynthesis. This suggests that the role of mitochondria to support photosynthesis is provided through either the alternative pathway or the cytochrome pathway, and when either pathway is inhibited, such as under environmental stress, a common, dramatic, and succinct mitochondrial signal is activated to alter energy metabolism in both organelles. aox1a:rpoTmp double mutants grown under optimal conditions showed dramatic reductions in biomass production compared with aox1a and rpoTmp and a transcriptome that was distinct from aox1a or rpoTmp. Transcript data indicating activation of mitochondrial biogenesis in aox1a:rpoTmp were supported by a proteomic analysis of over 200 proteins. Under optimal conditions, aox1a:rpoTmp plants seemed to switch on many of the typical mitochondrial stress regulators. Under adverse conditions, aox1a:rpoTmp turned off these responses and displayed a biotic stress response. Taken together, these results highlight the diverse signaling pathways activated by the

  7. Using the Skindex-16 and Common Terminology Criteria for Adverse Events to assess rash symptoms: results of a pooled-analysis (N0993)

    PubMed Central

    Burger, Kelli N.; Loprinzi, Charles L.; Wittich, Michelle A. Neben; Miller, Robert C.; Jatoi, Aminah; Sloan, Jeff A.

    2012-01-01

    Background Historically, skin toxicity has been assessed in prospective clinical trials using the clinician-reported National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). The patient-reported Skindex-16 measures symptoms and perceptions of toxicity. This study was designed to compare information provided by these two measures. Methods Data were compiled from three placebo-controlled North Central Cancer Treatment Group studies (N06C4, N03CB, N05C4) having rash prevention as the primary objective. All used the Skindex-16 and CTCAE at baseline, weekly during treatment and during a minimum 2-week follow-up period. Statistical procedures, including Pearson correlations, were utilized to determine relationships between adverse event (AE) grades and Skindex-16 scores. Results Four hundred and twelve individual patients provided data (median age, 61; 134 male). Patients’ Skindex-16 score results show a 0.9 overall mean (range 0–6 with 6 being worse symptoms), a 0.4 baseline mean (range, 0–4.3) and a 1.3 end-of-treatment mean (range, 0–5.9). Ninety-three, 142 and 177 patients experienced a grade 0, 1 and 2+ CTCAE skin toxicity, respectively. Baseline Skindex-16 scores had relatively low correlation with CTCAE grades. The correlation of rash grade with Skindex-16 scores ranged from r=0.49 with the function subscale to r=0.62 with the symptom subscale. The highest correlations of the maximum grade of any dermatological AE with the Skindex-16 were r=0.48 for the total score and r=0.55 for the symptom subscale. Conclusions The data reported support the decision to include both measures in a clinical trial to assess the patient experience, as each measure may specifically target varying symptoms and intensities. PMID:21922203

  8. Demographic Clusters Identified within the Northern Gulf of Mexico Common Bottlenose Dolphin (Tursiops truncates) Unusual Mortality Event: January 2010 - June 2013

    PubMed Central

    Venn-Watson, Stephanie; Garrison, Lance; Litz, Jenny; Fougeres, Erin; Mase, Blair; Rappucci, Gina; Stratton, Elizabeth; Carmichael, Ruth; Odell, Daniel; Shannon, Delphine; Shippee, Steve; Smith, Suzanne; Staggs, Lydia; Tumlin, Mandy; Whitehead, Heidi; Rowles, Teri

    2015-01-01

    A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana’s record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better

  9. Cognitive interviewing of the U.S. National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

    PubMed Central

    Hay, Jennifer L.; Atkinson, Thomas M.; Reeve, Bryce B.; Mitchell, Sandra A.; Mendoza, Tito R.; Willis, Gordon; Minasian, Lori M.; Clauser, Steven B.; Denicoff, Andrea; O’Mara, Ann; Chen, Alice; Bennett, Antonia V.; Paul, Diane B.; Gagne, Joshua; Rogak, Lauren; Sit, Laura; Viswanath, Vish; Schrag, Deborah; Basch, Ethan

    2013-01-01

    Purpose The National Cancer Institute’s Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) is a library of question items that enables patient reporting of adverse events (AEs) in clinical trials. This study contributes content validity evidence of the PRO-CTCAE by incorporating cancer patient input of the relevance and comprehensiveness of the item library. Methods Cognitive interviews were conducted among patients undergoing chemotherapy or radiation therapy at multiple sites to evaluate comprehension, memory retrieval, judgment, and response mapping related to AE terms (e.g., nausea); attribute terms (regarding frequency, severity, or interference); response options; and recall period. Three interview rounds were conducted with ≥20 patients completing each item per round. Items were modified and retested if ≥3 patients exhibited cognitive difficulties or if experienced by ≤25% patients. Results 127 patients participated (35% ≤high school; 28% non-white; 59% female). Most AE terms (63/80) generated no cognitive difficulties. The remaining 17 were modified without further difficulties by Round 3. Terms were comprehended regardless of education level. Attribute terms and response options required no modifications. Patient adherence to recall period (7-days) was improved when the reference period was incorporated. Conclusions This study provides evidence confirming comprehension of the U.S. English language versions of items in the PRO-CTCAE library for measuring symptomatic AEs from the patient perspective within the context of cancer treatment. Several minor changes were made to the items to improve item clarity, comprehension, and ease of response judgment. This study helps establish the content validity of PRO-CTCAE items for patient reporting of AEs during cancer treatment. PMID:23868457

  10. Demographic clusters identified within the northern Gulf of Mexico common bottlenose dolphin (Tursiops truncates) unusual mortality event: January 2010-June 2013.

    PubMed

    Venn-Watson, Stephanie; Garrison, Lance; Litz, Jenny; Fougeres, Erin; Mase, Blair; Rappucci, Gina; Stratton, Elizabeth; Carmichael, Ruth; Odell, Daniel; Shannon, Delphine; Shippee, Steve; Smith, Suzanne; Staggs, Lydia; Tumlin, Mandy; Whitehead, Heidi; Rowles, Teri

    2015-01-01

    A multi-year unusual mortality event (UME) involving primarily common bottlenose dolphins (Tursiops truncates) was declared in the northern Gulf of Mexico (GoM) with an initial start date of February 2010 and remains ongoing as of August 2014. To examine potential changing characteristics of the UME over time, we compared the number and demographics of dolphin strandings from January 2010 through June 2013 across the entire GoM as well as against baseline (1990-2009) GoM stranding patterns. Years 2010 and 2011 had the highest annual number of stranded dolphins since Louisiana's record began, and 2011 was one of the years with the highest strandings for both Mississippi and Alabama. Statewide, annual numbers of stranded dolphins were not elevated for GoM coasts of Florida or Texas during the UME period. Demographic, spatial, and temporal clusters identified within this UME included increased strandings in northern coastal Louisiana and Mississippi (March-May 2010); Barataria Bay, Louisiana (August 2010-December 2011); Mississippi and Alabama (2011, including a high prevalence and number of stranded perinates); and multiple GoM states during early 2013. While the causes of the GoM UME have not been determined, the location and magnitude of dolphin strandings during and the year following the 2010 Deepwater Horizon oil spill, including the Barataria Bay cluster from August 2010 to December 2011, overlap in time and space with locations that received heavy and prolonged oiling. There are, however, multiple known causes of previous GoM dolphin UMEs, including brevetoxicosis and dolphin morbillivirus. Additionally, increased dolphin strandings occurred in northern Louisiana and Mississippi before the Deepwater Horizon oil spill. Identification of spatial, temporal, and demographic clusters within the UME suggest that this mortality event may involve different contributing factors varying by location, time, and bottlenose dolphin populations that will be better discerned

  11. Neurological and behavioral abnormalities, ventricular dilatation, altered cellular functions, inflammation, and neuronal injury in brains of mice due to common, persistent, parasitic infection

    PubMed Central

    Hermes, Gretchen; Ajioka, James W; Kelly, Krystyna A; Mui, Ernest; Roberts, Fiona; Kasza, Kristen; Mayr, Thomas; Kirisits, Michael J; Wollmann, Robert; Ferguson, David JP; Roberts, Craig W; Hwang, Jong-Hee; Trendler, Toria; Kennan, Richard P; Suzuki, Yasuhiro; Reardon, Catherine; Hickey, William F; Chen, Lieping; McLeod, Rima

    2008-01-01

    Background Worldwide, approximately two billion people are chronically infected with Toxoplasma gondii with largely unknown consequences. Methods To better understand long-term effects and pathogenesis of this common, persistent brain infection, mice were infected at a time in human years equivalent to early to mid adulthood and studied 5–12 months later. Appearance, behavior, neurologic function and brain MRIs were studied. Additional analyses of pathogenesis included: correlation of brain weight and neurologic findings; histopathology focusing on brain regions; full genome microarrays; immunohistochemistry characterizing inflammatory cells; determination of presence of tachyzoites and bradyzoites; electron microscopy; and study of markers of inflammation in serum. Histopathology in genetically resistant mice and cytokine and NRAMP knockout mice, effects of inoculation of isolated parasites, and treatment with sulfadiazine or αPD1 ligand were studied. Results Twelve months after infection, a time equivalent to middle to early elderly ages, mice had behavioral and neurological deficits, and brain MRIs showed mild to moderate ventricular dilatation. Lower brain weight correlated with greater magnitude of neurologic abnormalities and inflammation. Full genome microarrays of brains reflected inflammation causing neuronal damage (Gfap), effects on host cell protein processing (ubiquitin ligase), synapse remodeling (Complement 1q), and also increased expression of PD-1L (a ligand that allows persistent LCMV brain infection) and CD 36 (a fatty acid translocase and oxidized LDL receptor that mediates innate immune response to beta amyloid which is associated with pro-inflammation in Alzheimer's disease). Immunostaining detected no inflammation around intra-neuronal cysts, practically no free tachyzoites, and only rare bradyzoites. Nonetheless, there were perivascular, leptomeningeal inflammatory cells, particularly contiguous to the aqueduct of Sylvius and hippocampus

  12. Analysis of the common deletions in the mitochondrial DNA is a sensitive biomarker detecting direct and non-targeted cellular effects of low dose ionizing radiation.

    PubMed

    Schilling-Tóth, Boglárka; Sándor, Nikolett; Kis, Eniko; Kadhim, Munira; Sáfrány, Géza; Hegyesi, Hargita

    2011-11-01

    One of the key issues of current radiation research is the biological effect of low doses. Unfortunately, low dose science is hampered by the unavailability of easily performable, reliable and sensitive quantitative biomarkers suitable detecting low frequency alterations in irradiated cells. We applied a quantitative real time polymerase chain reaction (qRT-PCR) based protocol detecting common deletions (CD) in the mitochondrial genome to assess direct and non-targeted effects of radiation in human fibroblasts. In directly irradiated (IR) cells CD increased with dose and was higher in radiosensitive cells. Investigating conditioned medium-mediated bystander effects we demonstrated that low and high (0.1 and 2Gy) doses induced similar levels of bystander responses and found individual differences in human fibroblasts. The bystander response was not related to the radiosensitivity of the cells. The importance of signal sending donor and signal receiving target cells was investigated by placing conditioned medium from a bystander response positive cell line (F11-hTERT) to bystander negative cells (S1-hTERT) and vice versa. The data indicated that signal sending cells are more important in the medium-mediated bystander effect than recipients. Finally, we followed long term effects in immortalized radiation sensitive (S1-hTERT) and normal (F11-hTERT) fibroblasts up to 63 days after IR. In F11-hTERT cells CD level was increased until 35 days after IR then reduced back to control level by day 49. In S1-hTERT cells the increased CD level was also normalized by day 42, however a second wave of increased CD incidence appeared by day 49 which was maintained up to day 63 after IR. This second CD wave might be the indication of radiation-induced instability in the mitochondrial genome of S1-hTERT cells. The data demonstrated that measuring CD in mtDNA by qRT-PCR is a reliable and sensitive biomarker to estimate radiation-induced direct and non-targeted effects. PMID:21843534

  13. Akt activation is a common event in pediatric malignant gliomas and a potential adverse prognostic marker: a report from the children’s oncology group

    PubMed Central

    Hamilton, Ronald L.; Murdoch, Geoffrey H.; Burger, Peter C.; Brat, Daniel J.; Rosenblum, Marc K.; Nikiforova, Marina N.; Holmes, Emiko J.; Zhou, Tianni; Cohen, Kenneth J.; Jakacki, Regina I.

    2010-01-01

    Aberrant activation of Akt is a common finding in adult malignant gliomas, resulting in most cases from mutations or deletions involving PTEN, which allows constitutive Akt phosphorylation. In contrast, we have previously reported that pediatric malignant gliomas, which are morphologically similar to lesions arising in adults, have a substantially lower incidence of genomic alterations of PTEN. The objective of this study was to determine whether Akt activation was also an uncommon finding in childhood malignant gliomas and whether this feature was associated with survival. To address this issue, we examined the frequency of Akt activation, determined by overexpression of the activated phosphorylated form of Akt (Se473) on immunohistochemical analysis, in a series of 53 childhood malignant gliomas obtained from newly diagnosed patients treated on the Children’s Oncology Group ACNS0126 and 0423 studies. The relationship between Akt activation and p53 over-expression, MIB1 labeling, and tumor histology was evaluated. The association between Akt activation and survival was also assessed. Overexpression of activated Akt was observed in 42 of 53 tumors, far in excess of the frequency of PTEN mutations we have previously observed. There was no association between Akt activation and either histology, p53 overexpression, or MIB1 proliferation indices. Although tumors that lacked Akt overexpression had a trend toward more favorable event-free survival and overall survival (p = 0.06), this association reflected that non-overexpressing tumors were significantly more likely to have undergone extensive tumor removal, which was independently associated with outcome. Activation of Akt is a common finding in pediatric malignant gliomas, although it remains uncertain whether this is an independent adverse prognostic factor. In view of the frequency of Akt activation, the evaluation of molecularly targeted therapies that inhibit this pathway warrants consideration for these tumors

  14. The role of dose rate in radiation cancer risk: evaluating the effect of dose rate at the molecular, cellular and tissue levels using key events in critical pathways following exposure to low LET radiation

    PubMed Central

    Brooks, Antone L.; Hoel, David G.; Preston, R. Julian

    2016-01-01

    Abstract Purpose: This review evaluates the role of dose rate on cell and molecular responses. It focuses on the influence of dose rate on key events in critical pathways in the development of cancer. This approach is similar to that used by the U.S. EPA and others to evaluate risk from chemicals. It provides a mechanistic method to account for the influence of the dose rate from low-LET radiation, especially in the low-dose region on cancer risk assessment. Molecular, cellular, and tissues changes are observed in many key events and change as a function of dose rate. The magnitude and direction of change can be used to help establish an appropriate dose rate effectiveness factor (DREF). Conclusions: Extensive data on key events suggest that exposure to low dose-rates are less effective in producing changes than high dose rates. Most of these data at the molecular and cellular level support a large (2–30) DREF. In addition, some evidence suggests that doses delivered at a low dose rate decrease damage to levels below that observed in the controls. However, there are some data human and mechanistic data that support a dose-rate effectiveness factor of 1. In summary, a review of the available molecular, cellular and tissue data indicates that not only is dose rate an important variable in understanding radiation risk but it also supports the selection of a DREF greater than one as currently recommended by ICRP (2007) and BEIR VII (NRC/NAS 2006). PMID:27266588

  15. Variety Is Not the Spice of Life for People with Autism Spectrum Disorders: Frequency Ratings of Central, Variable and Inappropriate Aspects of Common Real-Life Events

    ERIC Educational Resources Information Center

    Loth, Eva; Happe, Francesca; Gomez, Juan Carlos

    2010-01-01

    This study used a novel rating task to investigate whether high-functioning individuals with autism spectrum disorder (ASD) have difficulties distinguishing essential from variable aspects of familiar events. Participants read stories about everyday events and judged how often central, variable, and inappropriate event-components normally occur in…

  16. Common and segregated neural substrates for automatic conceptual and affective priming as revealed by event-related functional magnetic resonance imaging.

    PubMed

    Liu, Hongyan; Hu, Zhiguo; Peng, Danling; Yang, Yanhui; Li, Kuncheng

    2010-02-01

    The brain activity associated with automatic semantic priming has been extensively studied. Thus far there has been no prior study that directly contrasts the neural mechanisms of semantic and affective priming. The present study employed event-related fMRI to examine the common and distinct neural bases underlying conceptual and affective priming with a lexical decision task. A special type of emotional word, a dual-meaning word containing both conceptual meaning and affective meaning, was adopted as target. Short stimulus onset asynchrony (SOA) (50 ms) was used to emphasize automatic processing. Fifteen participants were scanned in the present study. We found that the left middle/superior temporal gyrus was the brain region involved in both automatic conceptual and affective priming effects, suggesting general lexical-semantic processing that share in the two types of priming. The left inferior frontal gyrus and right superior temporal gyrus were found to be the conceptual-specific areas in automatic priming effect, consistent with the role of these areas in more extensive within-category semantic processes. The results also revealed that the left fusiform gyrus and left insula were the affective-specific regions in automatic priming effect, demonstrating the involvement of the left fusiform gyrus in automatic affective priming effect, and clarifying the role of the insula in emotional processing rather than conceptual processing. Despite comparable behavioral effects of automatic conceptual priming and affective priming, the present study revealed a neural dissociation of the two types of priming, as well as the shared neural bases. PMID:20018360

  17. Population structure within lineages of Wheat streak mosaic virus derived from a common founding event exhibits stochastic variation inconsistent with the deterministic quasi-species model

    SciTech Connect

    French, Roy; Stenger, Drake C. . E-mail: dstenger@unlnotes.unl.edu

    2005-12-20

    Structure of Wheat streak mosaic virus (WSMV) populations derived from a common founding event and subjected to serial passage at high multiplicity of infection (MOI) was evaluated. The founding population was generated by limiting dilution inoculation. Lineages of known pedigree were sampled at passage 9 (two populations) and at passage 15, with (three populations) or without mixing (four populations) of lineages at passage 10. Polymorphism within each population was assessed by sequencing 17-21 clones containing a 1371 nt region (WSMV-Sidney 81 nts 8001-9371) encompassing the entire coat protein cistron and flanking regions. Mutation frequency averaged {approx}5.0 x 10{sup -4}/nt across all populations and ranged from 2.4 to 11.6 x 10{sup -4}/nt within populations, but did not consistently increase or decrease with the number of passages removed from the founding population. Shared substitutions (19 nonsynonymous, 10 synonymous, and 3 noncoding) occurred at 32 sites among 44 haplotypes. Only four substitutions became fixed (frequency = 100%) within a population and nearly one third (10/32) never achieved a frequency of 10% or greater in any sampled population. Shared substitutions were randomly distributed with respect to genome position, with transitions outnumbering transversions 5.4:1 and a clear bias for A to G and U to C substitutions. Haplotype composition of each population was unique with complexity of each population varying unpredictably, in that the number and frequency of haplotypes within a lineage were not correlated with number of passages removed from the founding population or whether the population was derived from a single or mixed lineage. The simplest explanation is that plant virus lineages, even those propagated at high MOI, are subject to frequent, narrow genetic bottlenecks during systemic movement that result in low effective population size and stochastic changes in population structure upon serial passage.

  18. Genomic losses at 5q13.2 and 8p23.1 in dysplastic hepatocytes are common events in hepatitis B virus-related hepatocellular carcinoma

    PubMed Central

    ZHAO, ZHANG; CHEN, GUANG-YONG; LONG, JIANG; LI, HAI; HUANG, JIAN

    2015-01-01

    Chromosomal loci with genomic imbalances are frequently identified in hepatocellular carcinoma (HCC). Greater than two-thirds of hepatitis B virus (HBV)-related HCCs originate from liver cirrhosis following a duration of up to two decades. However, it is unclear whether these genomic imbalances occur and accumulate in dysplastic hepatocytes of the cirrhotic liver during the progression from regenerated nodules to preneoplastic lesions, including dysplastic nodules (DN). In the present study, high-grade DNs (HGDNs) of HBV-related liver cirrhosis were screened to identify loci with genomic imbalances, and the frequency of the identified loci in a group of HCCs was analyzed in order to determine whether there may be a genetic link between liver cirrhosis and HCC. Genomic DNA was extracted from six HGDNs of two cases of HBV-related liver cirrhosis and subjected to array comparative genomic hybridization (CGH) analysis with a NimbleGen 720K microarray. Loci with the most frequently observed genomic imbalances in DNs were further analyzed in 83 cases of HCC by differential polymerase chain reaction (PCR) and quantitative PCR. The array CGH analysis revealed that the majority of genomic imbalances in the HGDNs were genomic losses of small segments, with loss of heterozygosity (LOH) at 5q13.2 and 8p23.1 identified most frequently. Of the 83 HCC cases, 30 (36.1%) cases were identified with LOH at 5q13.2, where known tumor-associated genes are located, including general transcription factor IIH subunit 2 (GTF2H2), baculoviral IAP repeat-containing protein 1 (BIRC1) and occludin (OCLN). LOH frequency at 8p23.1 in HCC was 61.29% (D8S1130) and 68.4% (D8S503) respectively, similar to the results obtained in previous studies. In conclusion, the results of the present study provided evidence that genomic losses at 5q13.2 and 8p23.1 identified in dysplastic hepatocytes of the cirrhotic liver are common events in HCC. HCC-associated chromosomal abnormalities may occur and accumulate

  19. Cosmogenic Noble Gases and Their Production Rates in Eucrites, Diogenites, and Howardites: Common Asteroid Break-up Events 38 Ma, 21 Ma, and 6 MA Ago

    NASA Astrophysics Data System (ADS)

    Eugster, O.; Michel, Th.

    1993-07-01

    It is likely that the eucrites and their associates, the howardites and diogenites, sample the surface and shallow interior of a single parent body, possibly 4 Vesta (cf. [1] and [2]). A break-up event that reaches deep enough may, thus, eject asteroidal fragments representing meteorites from all three classes. In this work we present a comprehensive investigation of the exposure age clusters for howardites, eucrites, and diogenites (HEDs). Cosmic-ray exposure ages critically depend on the production rates for cosmic-ray produced nuclei. For eucrites shielding independent production rates for ^21Ne and ^38Ar have been determined previously [3,4]. We now present production rates of ^3He, ^21Ne, ^33Ar, ^78Kr, ^83Kr, and ^126Xe for eucrites, howardites, and diogenites as a function of shielding, where appropriate, and of target element abundances as derived on the basis of ^81Kr-Kr ages. E.g., for ^21Ne we obtain: P(sub)21 (EUC) = 8.43 P^1(sub)21 [16.1 (^22Ne/^21Ne)(sub)c - 10.3]^-1, P(sub)21 (HOW) = 6.16 P^1(sub)21 [18.1 (^22Ne/^21Ne)(sub)c - 14.1]^-1, P(sub)21 (DIO) = 4.81 P^1(sub)21 [25.7 (^22Ne/^21Ne)(sub)c - 23.7]^-1, where P^1(sub)21 = 1.63 [Mg] + 0.6 [Al] + 0.32 [Si] + 0.22 [S] + 0.07 [Ca] + 0.021 [Fe + Ni] as given by [3]. (Elemental abundance [x] in weight %, P(sub)21 in 10^10 cm^3 STP/g, Ma). Average cosmic-ray exposure ages were derived from as many nuclei as possible for 14 HEDs analyzed by us (see also [5,6]) and for those compiled by [7]. Two major exposure age clusters at 21 and 38 Ma are represented in all three meteorite classes (Fig. 1). In the cluster at 21 +- 4 Ma are 12 out of 39 eucrites, 6 out of 14 howardites, and 7out of 12 diogenites. In the cluster at 38 +- 8 Ma are 6 eucrites, 5 howardites, and 4 diogenites. A third common break-up event at 5 +- 1 Ma is indicated by the remaining diogenite, three eucrites, and one howardite. Schultz [8] found major clusters for eucrites at 13, 21, 26, and 40 Ma for howardites around 10 and 24 Ma, and for

  20. In Vivo Implanted Bone Marrow-Derived Mesenchymal Stem Cells Trigger a Cascade of Cellular Events Leading to the Formation of an Ectopic Bone Regenerative Niche

    PubMed Central

    Tasso, Roberta; Ulivi, Valentina; Reverberi, Daniele; Lo Sicco, Claudia; Descalzi, Fiorella

    2013-01-01

    We recently reported that mouse bone marrow stromal cells, also known as bone marrow (BM)-derived mesenchymal stem cells (MSCs), seeded onto a scaffold and implanted in vivo, led to an ectopic bone deposition by host cells. This MSCs capacity was critically dependent on their commitment level, being present only in MSCs cultured in presence of fibroblast growth factor-2. Taking advantage of a chimeric mouse model, in this study we show that seeded MSCs trigger a cascade of events resulting in the mobilization of macrophages, the induction of their functional switch from a proinflammatory to a proresolving phenotype, and the subsequent formation of a bone regenerative niche through the recruitment, within the first 2 weeks of implantation, of endothelial progenitors and of cells with an osteogenic potential (CD146+CD105+), both of them derived from the BM. Moreover, we demonstrated that, in an inflammatory environment, MSCs secrete a large amount of prostaglandin E2 playing a key role in the macrophage phenotype switch. PMID:23924051

  1. Cellular Homeostasis and Aging.

    PubMed

    Hartl, F Ulrich

    2016-06-01

    Aging and longevity are controlled by a multiplicity of molecular and cellular signaling events that interface with environmental factors to maintain cellular homeostasis. Modulation of these pathways to extend life span, including insulin-like signaling and the response to dietary restriction, identified the cellular machineries and networks of protein homeostasis (proteostasis) and stress resistance pathways as critical players in the aging process. A decline of proteostasis capacity during aging leads to dysfunction of specific cell types and tissues, rendering the organism susceptible to a range of chronic diseases. This volume of the Annual Review of Biochemistry contains a set of two reviews addressing our current understanding of the molecular mechanisms underlying aging in model organisms and humans. PMID:27050288

  2. Adaptive and maladaptive mechanisms of cellular priming.

    PubMed Central

    Meldrum, D R; Cleveland, J C; Moore, E E; Partrick, D A; Banerjee, A; Harken, A H

    1997-01-01

    OBJECTIVE: The mechanisms of cellular priming resulting in both adaptive and maladaptive responses to subsequent injury and strategies for manipulating this priming to constructive therapeutic advantage are explored. BACKGROUND DATA: A cell is prepared or educated by an initial insult (priming stimulus). Investigations in both laboratory animals and humans indicate that cells, organs, and perhaps even whole patients respond differently to a proximal second insult ("second hit") by virtue of this prior environmental history. The opportunity to achieve the primed state appears to be conserved across almost all cell types. The initial stimulus transmits a message to the cellular machinery that influences the cell's response to a subsequent challenge. This response may result in an exaggerated inflammatory response in the case of the neutrophil (an often maladaptive process) or an improved tolerance to injury by the myocyte (adaptive response). Our global hypothesis is that cellular priming is a conserved, receptor-dependent process that invokes common intracellular targets across multiple cell types. We further postulate that these targets create a language based on the transient phosphorylation and dephosphorylation of intracellular enzymes that is therapeutically accessible. CONCLUSIONS: Priming is a conserved, receptor-dependent process transduced by means of intracellular targets across multiple cell types. The potential therapeutic strategies outlined involve the receptor-mediated manipulation of cellular events. These events are transmitted through an intracellular language that instructs the cell regarding its behavior in response to subsequent stimulation. Understanding these intracellular events represents a realistic goal of priming and preconditioning biology and will likely lead to clinical control of the primed state. PMID:9389392

  3. Flooding of the Great River during the Common Era: A Paleohydrological Record of High Magnitude Flood Events from the Central Mississippi River Valley

    NASA Astrophysics Data System (ADS)

    Williams, J. W.; Munoz, S. E.; Gruley, K. E.; Massie, A.

    2014-12-01

    Streamflow characteristics are known to be sensitive to changes in climate, but few continuous records of flooding exist to evaluate the response of hydrological systems to centennial- and millennia-scale climate changes. Here, we present sedimentary records from two oxbow lakes (Horseshoe Lake and Grassy Lake, Illinois, USA) in the central Mississippi River valley (CMRV) that display abrupt shifts in sediment composition and particle-size consistent with deposition by floodwaters immediately following inundation of the floodplain. The sedimentary record at Horseshoe Lake begins ca. AD 100 and displays five major flood events, with four of these occurring after ca. AD 1100. Situated 200 km downstream, the record from Grassy Lake begins later, ca. AD 800, and also shows four major flood events after ca. AD 1100. An analysis of synchronicity using Bayesian age modelling software shows high likelihoods that the four overlapping flood events occurred at the same time, confirming that these events resulted from flooding of the Mississippi River. The most recent event we record at AD 1840 ± 50 corresponds to the AD 1844 flood, the largest flood by discharge (37 m3/s) measured by the gauging station at St. Louis, Missouri, indicating that our sedimentary records document high magnitude flood events. Together, our two sedimentary records show a major shift in the frequency of high magnitude flooding in the central Mississippi River at ca. AD 1100. From AD 100 - AD 1100, only one relatively subtle flood event is recorded, but from AD 1100 - AD 1900, four high magnitude floods deposited distinctive sediment at both sites. The period of infrequent flooding corresponds to a time of agricultural intensification and population growth in the CMRV, while the entire region was abandoned when flood frequency increased. The pronounced shift in flood frequency we observe in our records at ca. AD 1100 begins during the Medieval Climate Anomaly (MCA; AD 950 - AD 1250), a period of

  4. Architected Cellular Materials

    NASA Astrophysics Data System (ADS)

    Schaedler, Tobias A.; Carter, William B.

    2016-07-01

    Additive manufacturing enables fabrication of materials with intricate cellular architecture, whereby progress in 3D printing techniques is increasing the possible configurations of voids and solids ad infinitum. Examples are microlattices with graded porosity and truss structures optimized for specific loading conditions. The cellular architecture determines the mechanical properties and density of these materials and can influence a wide range of other properties, e.g., acoustic, thermal, and biological properties. By combining optimized cellular architectures with high-performance metals and ceramics, several lightweight materials that exhibit strength and stiffness previously unachievable at low densities were recently demonstrated. This review introduces the field of architected materials; summarizes the most common fabrication methods, with an emphasis on additive manufacturing; and discusses recent progress in the development of architected materials. The review also discusses important applications, including lightweight structures, energy absorption, metamaterials, thermal management, and bioscaffolds.

  5. System Safety Common Cause Analysis

    Energy Science and Technology Software Center (ESTSC)

    1992-03-10

    The COMCAN fault tree analysis codes are designed to analyze complex systems such as nuclear plants for common causes of failure. A common cause event, or common mode failure, is a secondary cause that could contribute to the failure of more than one component and violates the assumption of independence. Analysis of such events is an integral part of system reliability and safety analysis. A significant common cause event is a secondary cause common tomore » all basic events in one or more minimal cut sets. Minimal cut sets containing events from components sharing a common location or a common link are called common cause candidates. Components share a common location if no barrier insulates any one of them from the secondary cause. A common link is a dependency among components which cannot be removed by a physical barrier (e.g.,a common energy source or common maintenance instructions).« less

  6. Multi-event capture-recapture modeling of host-pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns.

    PubMed

    Santoro, Simone; Pacios, Isa; Moreno, Sacramento; Bertó-Moran, Alejandro; Rouco, Carlos

    2014-01-01

    Host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host-pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  7. Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

    PubMed Central

    2014-01-01

    Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  8. Cellular resilience.

    PubMed

    Smirnova, Lena; Harris, Georgina; Leist, Marcel; Hartung, Thomas

    2015-01-01

    Cellular resilience describes the ability of a cell to cope with environmental changes such as toxicant exposure. If cellular metabolism does not collapse directly after the hit or end in programmed cell death, the ensuing stress responses promote a new homeostasis under stress. The processes of reverting "back to normal" and reversal of apoptosis ("anastasis") have been studied little at the cellular level. Cell types show astonishingly similar vulnerability to most toxicants, except for those that require a very specific target, metabolism or mechanism present only in specific cell types. The majority of chemicals triggers "general cytotoxicity" in any cell at similar concentrations. We hypothesize that cells differ less in their vulnerability to a given toxicant than in their resilience (coping with the "hit"). In many cases, cells do not return to the naive state after a toxic insult. The phenomena of "pre-conditioning", "tolerance" and "hormesis" describe this for low-dose exposures to toxicants that render the cell more resistant to subsequent hits. The defense and resilience programs include epigenetic changes that leave a "memory/scar" - an alteration as a consequence of the stress the cell has experienced. These memories might have long-term consequences, both positive (resistance) and negative, that contribute to chronic and delayed manifestations of hazard and, ultimately, disease. This article calls for more systematic analyses of how cells cope with toxic perturbations in the long-term after stressor withdrawal. A technical prerequisite for these are stable (organotypic) cultures and a characterization of stress response molecular networks. PMID:26536287

  9. The Common Core.

    ERIC Educational Resources Information Center

    Boyer, Ernest L.

    Current curricula in institutions of higher education are criticized in this speech for their lack of a common core of education. Several possibilities for developing such a common core include education centered around our common heritage and the challenges of the present. It is suggested that all students must be introduced to the events,…

  10. Real-time analysis of the detailed sequence of cellular events in mAb-mediated complement-dependent cytotoxicity of B-cell lines and of chronic lymphocytic leukemia B-cells.

    PubMed

    Lindorfer, Margaret A; Cook, Erika M; Tupitza, Jillian C; Zent, Clive S; Burack, Richard; de Jong, Rob N; Beurskens, Frank J; Schuurman, Janine; Parren, Paul W H I; Taylor, Ronald P

    2016-02-01

    Complement-dependent cytotoxicity is an important mechanism of action of certain mAbs used in cancer immunotherapy, including ofatumumab and rituximab. However, the detailed sequence of cellular changes that occur in nucleated cells attacked by mAb and complement has not been delineated. Recently developed CD20 mAbs, engineered to form hexamers on binding to cells, react with B-cells in serum, chelate C1q, and then activate complement and promote cell killing considerably more effectively than their wild-type precursors. We used these engineered mAbs as a model to investigate the sequence of events that occur when mAbs bind to B-cell lines and to primary cells from patients with chronic lymphocytic leukemia and then activate complement. Based on four-color confocal microscopy real-time movies and high resolution digital imaging, we find that after CD20 mAb binding and C1q uptake, C3b deposits on cells, followed by Ca(2+) influx, revealed by bright green signals generated on cells labeled with FLUO-4, a Ca(2+) indicator. The bright FLUO-4/Ca(2+) signal fades, replaced by punctate green signals in mitochondria, indicating Ca(2+) localization. This step leads to mitochondrial poisoning followed by cell death. The entire sequence is completed in <2 min for hexamerization-enhanced CD20 mAb-mediated killing. To our knowledge this is the first time the entire process has been characterized in detail in real time. By identifying multiple discrete steps in the cytotoxic pathway for nucleated cells our findings may inform future development and more effective application of complement-fixing mAbs to cancer treatment. PMID:26690706

  11. Common Space, Common Time, Common Work

    ERIC Educational Resources Information Center

    Shank, Melody J.

    2005-01-01

    The most valued means of support and learning cited by new teachers at Poland Regional High School in rural Maine are the collegial interactions that common workspace, common planning time, and common tasks make possible. The school has used these everyday structures to enable new and veteran teachers to converse about curricular and pedagogical…

  12. Fabrication of cellular materials

    NASA Astrophysics Data System (ADS)

    Prud'homme, Robert K.; Aksay, Ilhan A.; Garg, Rajeev

    1996-02-01

    Nature uses cellular materials in applications requiring strength while, simultaneously, minimizing raw materials requirements. Minimizing raw materials is efficient both in terms of the energy expended by the organism to synthesize the structure and in terms of the strength- to-weight ratio of the structure. Wood is the most obvious example of cellular bio-materials, and it is the focus of other presentations in this symposium. The lightweight bone structure of birds is another excellent example where weight is a key criterion. The anchoring foot of the common muscle [Mytilus edulis] whereby it attaches itself to objects is a further example of a biological system that uses a foam to fill space and yet conserve on raw materials. In the case of the muscle the foam is water filled and the foot structure distributes stress over a larger area so that the strength of the byssal thread from which it is suspended is matched to the strength of interfacial attachment of the foot to a substrate. In these examples the synthesis and fabrication of the cellular material is directed by intercellular, genetically coded, biochemical reactions. The resulting cell sizes are microns in scale. Cellular materials at the next larger scale are created by organisms at the next higher level of integration. For example an African tree frog lays her eggs in a gas/fluid foam sack she builds on a branch overhanging a pond. The outside of the foam sack hardens in the sun and prevents water evaporation. The foam structure minimizes the amount of fluid that needs to be incorporated into the sack and minimizes its weight. However, as far as the developing eggs are concerned, they are in an aqueous medium, i.e. the continuous fluid phase of the foam. After precisely six days the eggs hatch, and the solidified outer wall re-liquefies and dumps the emerging tadpoles into the pond below. The bee honeycomb is an example of a cellular material with exquisite periodicity at millimeter length scales. The

  13. Common Schools for Common Education.

    ERIC Educational Resources Information Center

    Callan, Eamonn

    1995-01-01

    A vision of common education for citizens of a liberal democracy warrants faith in common schools as an instrument of social good. Some kinds of separate schooling are not inconsistent with common schooling and are even desirable. Equal respect, as defined by J. Rawls, is a basis for common education. (SLD)

  14. 47 CFR 22.911 - Cellular geographic service area.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular geographic service area. 22.911 Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The Cellular Geographic Service Area (CGSA) of...

  15. 47 CFR 22.911 - Cellular geographic service area.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular geographic service area. 22.911 Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The Cellular Geographic Service Area (CGSA) of...

  16. 47 CFR 22.911 - Cellular geographic service area.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular geographic service area. 22.911 Section 22.911 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.911 Cellular geographic service area. The Cellular Geographic Service Area (CGSA) of...

  17. Common Cold

    MedlinePlus

    ... coughing - everyone knows the symptoms of the common cold. It is probably the most common illness. In ... people in the United States suffer 1 billion colds. You can get a cold by touching your ...

  18. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22... application competing against a cellular renewal application must contain, when initially filed,...

  19. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22... application competing against a cellular renewal application must contain, when initially filed,...

  20. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22... application competing against a cellular renewal application must contain, when initially filed,...

  1. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22... application competing against a cellular renewal application must contain, when initially filed,...

  2. 47 CFR 22.939 - Site availability requirements for applications competing with cellular renewal applications.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22... application competing against a cellular renewal application must contain, when initially filed,...

  3. Clays, common

    USGS Publications Warehouse

    Virta, R.L.

    1998-01-01

    Part of a special section on the state of industrial minerals in 1997. The state of the common clay industry worldwide for 1997 is discussed. Sales of common clay in the U.S. increased from 26.2 Mt in 1996 to an estimated 26.5 Mt in 1997. The amount of common clay and shale used to produce structural clay products in 1997 was estimated at 13.8 Mt.

  4. Continuum representations of cellular solids

    SciTech Connect

    Neilsen, M.K.

    1993-09-01

    Cellular materials consist of interconnected struts or plates which form cells. The struts or plates are constructed from a variety of metals, polymers, ceramics and wood products. Cellular materials are often used in impact limiters for shipping containers to protect the contents from accidental impact events. These materials exhibit a variety of complex behavior when subjected to crushing loads. This research focuses on the development of continuum representations of cellular solids that can be used in the finite element analysis of shipping container accidents. A significant portion of this work is the development of a new methodology to relate localized deformations to appropriate constitutive descriptions. This methodology provides the insight needed to select constitutive descriptions for cellular solids that capture the localized deformations that are observed experimentally. Constitutive relations are developed for two different cellular materials, aluminum honeycomb and polyurethane foam. These constitutive relations are based on plasticity and continuum damage theories. Plasticity is used to describe the permanent deformation exhibited by both aluminum honeycomb and polyurethane foam. Continuum damage is needed to capture the change in elastic parameters due to cracking of the polyurethane cell wall materials. The new constitutive description of polyurethane foam is implemented in both static and dynamic finite element codes, and analytical and numerical predictions are compared with available experimental data.

  5. Student Commons

    ERIC Educational Resources Information Center

    Gordon, Douglas

    2010-01-01

    Student commons are no longer simply congregation spaces for students with time on their hands. They are integral to providing a welcoming environment and effective learning space for students. Many student commons have been transformed into spaces for socialization, an environment for alternative teaching methods, a forum for large group meetings…

  6. Common Cause Failures and Ultra Reliability

    NASA Technical Reports Server (NTRS)

    Jones, Harry W.

    2012-01-01

    A common cause failure occurs when several failures have the same origin. Common cause failures are either common event failures, where the cause is a single external event, or common mode failures, where two systems fail in the same way for the same reason. Common mode failures can occur at different times because of a design defect or a repeated external event. Common event failures reduce the reliability of on-line redundant systems but not of systems using off-line spare parts. Common mode failures reduce the dependability of systems using off-line spare parts and on-line redundancy.

  7. Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation.

    PubMed

    Okamoto, Marina; Yamada, Lixy; Fujisaki, Yukie; Bloomfield, Gareth; Yoshida, Kentaro; Kuwayama, Hidekazu; Sawada, Hitoshi; Mori, Toshiyuki; Urushihara, Hideko

    2016-07-01

    Fertilization is a central event in sexual reproduction, and understanding its molecular mechanisms has both basic and applicative biological importance. Recent studies have uncovered the molecules that mediate this process in a variety of organisms, making it intriguing to consider conservation and evolution of the mechanisms of sexual reproduction across phyla. The social amoeba Dictyostelium discoideum undergoes sexual maturation and forms gametes under dark and humid conditions. It exhibits three mating types, type-I, -II, and -III, for the heterothallic mating system. Based on proteome analyses of the gamete membranes, we detected expression of two homologs of the plant fertilization protein HAP2-GCS1. When their coding genes were disrupted in type-I and type-II strains, sexual potency was completely lost, whereas disruption in the type-III strain did not affect mating behavior, suggesting that the latter acts as female in complex organisms. Our results demonstrate the highly conserved function of HAP2-GCS1 in gamete interactions and suggest the presence of additional allo-recognition mechanisms in D. discoideum gametes. PMID:27189178

  8. Aging, Cellular Senescence, and Cancer

    PubMed Central

    Campisi, Judith

    2014-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyper-plastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  9. Aging, cellular senescence, and cancer.

    PubMed

    Campisi, Judith

    2013-01-01

    For most species, aging promotes a host of degenerative pathologies that are characterized by debilitating losses of tissue or cellular function. However, especially among vertebrates, aging also promotes hyperplastic pathologies, the most deadly of which is cancer. In contrast to the loss of function that characterizes degenerating cells and tissues, malignant (cancerous) cells must acquire new (albeit aberrant) functions that allow them to develop into a lethal tumor. This review discusses the idea that, despite seemingly opposite characteristics, the degenerative and hyperplastic pathologies of aging are at least partly linked by a common biological phenomenon: a cellular stress response known as cellular senescence. The senescence response is widely recognized as a potent tumor suppressive mechanism. However, recent evidence strengthens the idea that it also drives both degenerative and hyperplastic pathologies, most likely by promoting chronic inflammation. Thus, the senescence response may be the result of antagonistically pleiotropic gene action. PMID:23140366

  10. Common cold

    MedlinePlus

    ... are the most common reason that children miss school and parents miss work. Parents often get colds ... other children. A cold can spread quickly through schools or daycares. Colds can occur at any time ...

  11. Cellular Stress Responses and Monitored Cellular Activities.

    PubMed

    Sawa, Teiji; Naito, Yoshifumi; Kato, Hideya; Amaya, Fumimasa

    2016-08-01

    To survive, organisms require mechanisms that enable them to sense changes in the outside environment, introduce necessary responses, and resist unfavorable distortion. Consequently, through evolutionary adaptation, cells have become equipped with the apparatus required to monitor their fundamental intracellular processes and the mechanisms needed to try to offset malfunction without receiving any direct signals from the outside environment. It has been shown recently that eukaryotic cells are equipped with a special mechanism that monitors their fundamental cellular functions and that some pathogenic proteobacteria can override this monitoring mechanism to cause harm. The monitored cellular activities involved in the stressed intracellular response have been researched extensively in Caenorhabditis elegans, where discovery of an association between key mitochondrial activities and innate immune responses was named "cellular associated detoxification and defenses (cSADD)." This cellular surveillance pathway (cSADD) oversees core cellular activities such as mitochondrial respiration and protein transport into mitochondria, detects xenobiotics and invading pathogens, and activates the endocrine pathways controlling behavior, detoxification, and immunity. The cSADD pathway is probably associated with cellular responses to stress in human inflammatory diseases. In the critical care field, the pathogenesis of lethal inflammatory syndromes (e.g., respiratory distress syndromes and sepsis) involves the disturbance of mitochondrial respiration leading to cell death. Up-to-date knowledge about monitored cellular activities and cSADD, especially focusing on mitochondrial involvement, can probably help fill a knowledge gap regarding the pathogenesis of lethal inflammatory syndromes in the critical care field. PMID:26954943

  12. Cellular Phone Towers

    MedlinePlus

    ... the call. How are people exposed to the energy from cellular phone towers? As people use cell ... where people can be exposed to them. The energy from a cellular phone tower antenna, like that ...

  13. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-01-01

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young's modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  14. Hierarchical cellular materials

    SciTech Connect

    Gibson, L.J.

    1991-12-31

    In this paper a method for estimating the contributions of both the composite and the cellular microstructures to the overall material properties and the mechanical efficiency of natural cellular solids will be described. The method will be demonstrated by focusing on the Young`s modulus; similar techniques can be used for other material properties. The results suggest efficient microstructures for engineered cellular materials.

  15. 47 CFR 22.917 - Emission limitations for cellular equipment.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Emission limitations for cellular equipment. 22.917 Section 22.917 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.917 Emission limitations for cellular equipment. The rules in this section...

  16. 47 CFR 22.901 - Cellular service requirements and limitations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular service requirements and limitations. 22.901 Section 22.901 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.901 Cellular service requirements and limitations. The licensee of each...

  17. Making the Common Good Common

    ERIC Educational Resources Information Center

    Chase, Barbara

    2011-01-01

    How are independent schools to be useful to the wider world? Beyond their common commitment to educate their students for meaningful lives in service of the greater good, can they educate a broader constituency and, thus, share their resources and skills more broadly? Their answers to this question will be shaped by their independence. Any…

  18. Modelling cellular behaviour

    NASA Astrophysics Data System (ADS)

    Endy, Drew; Brent, Roger

    2001-01-01

    Representations of cellular processes that can be used to compute their future behaviour would be of general scientific and practical value. But past attempts to construct such representations have been disappointing. This is now changing. Increases in biological understanding combined with advances in computational methods and in computer power make it possible to foresee construction of useful and predictive simulations of cellular processes.

  19. Probing intra-cellular drug release event using activatable (OFF/ON) CdS:Mn/ZnS quantum dots (Qdots): spectroscopic studies to investigate interaction of Qdots with quencher

    NASA Astrophysics Data System (ADS)

    Tharkur, Jeremy; Teblum, Andrew; Basumallick, Srijita; Shah, Rikhav; Cantarero, Karishma; Maity, Niharika; Rifai, Sara; Doshi, Mona; Gesquiere, Andre J.; Santra, Swadeshmukul

    2013-02-01

    In recent years, activatable Quantum Dots (AQdots) are gaining popularity in a number of chemical and biological sensing applications. A basic design of AQdot probes involves a suitable quencher which is capable of altering optical properties of the Qdots. In our previous studies we have shown that CdS:Mn/ZnS fluorescence can be effectively quenched using small molecule quenchers (such as dopamine, chemotherapeutic drug) as well as iron oxide nanoparticle via electron/energy transfer process. We have also shown that the quenched Qdot fluorescence can be restored when the Qdots are separated from the quencher. Using Qdot based activatable probes, we detected intracellular drug release event. Qdot fluorescence was restored upon interaction with the intracellular glutathione (GSH). In this paper, we report a GSH induced quenching of water-soluble N-Acetyl Cysteine (NAC) surface-conjugated Cds:Mn/ZnS Qdots. Quenching of NAC-Qdots was due to aggregation of Qdots in solution. This aggregation induced fluorescence quenching phenomenon resembles with the self-quenching phenomenon of traditional organic fluorescence dyes at high concentrations. UV-VIS and fluorescence emission spectroscopy data support the interaction and binding of GSH with the NAC-Qdots. Increase in particle size due to GSH induced aggregation of NAC-Qdots was confirmed by the Dynamic Light Scattering (DLS) data.

  20. Leucocyte cellular adhesion molecules.

    PubMed

    Yong, K; Khwaja, A

    1990-12-01

    Leucocytes express adhesion promoting receptors which mediate cell-cell and cell-matrix interactions. These adhesive interactions are crucial to the regulation of haemopoiesis and thymocyte maturation, the direction and control of leucocyte traffic and migration through tissues, and in the development of immune and non-immune inflammatory responses. Several families of adhesion receptors have been identified (Table). The leucocyte integrin family comprises 3 alpha beta heterodimeric membrane glycoproteins which share a common beta subunit, designated CD18. The alpha subunits of each of the 3 members, lymphocyte function associated antigen-1 (LFA-1), macrophage antigen-1 (Mac-1) and p150,95 are designated CD11a, b and c respectively. These adhesion molecules play a critical part in the immune and inflammatory responses of leucocytes. The leucocyte integrin family is, in turn, part of the integrin superfamily, members of which are evolutionally, structurally and functionally related. Another Integrin subfamily found on leucocytes is the VLA group, so-called because the 'very late activation antigens' VLA-1 and VLA-2 were originally found to appear late in T-cell activation. Members of this family function mainly as extracellular matrix adhesion receptors and are found both on haemopoietic and non-haemopoietic cells. They play a part in diverse cellular functions including tissue organisation, lymphocyte recirculation and T-cell immune responses. A third integrin subfamily, the cytoadhesins, are receptors on platelets and endothelial cells which bind extracellular matrix proteins. A second family of adhesion receptors is the immunoglobulin superfamily, members of which include CD2, LFA-3 and ICAM-1, which participate in T-cell adhesive interactions, and the antigen-specific receptors of T and B cells, CD4, CD8 and the MHC Class I and II molecules. A recently recognised family of adhesion receptors is the selectins, characterised by a common lectin domain. Leucocyte

  1. Activating Event Knowledge

    PubMed Central

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension. PMID:19298961

  2. Hyperglycemia Induces Cellular Hypoxia through Production of Mitochondrial ROS Followed by Suppression of Aquaporin-1

    PubMed Central

    Sada, Kiminori; Nishikawa, Takeshi; Kukidome, Daisuke; Yoshinaga, Tomoaki; Kajihara, Nobuhiro; Sonoda, Kazuhiro; Senokuchi, Takafumi; Motoshima, Hiroyuki; Matsumura, Takeshi; Araki, Eiichi

    2016-01-01

    We previously proposed that hyperglycemia-induced mitochondrial reactive oxygen species (mtROS) generation is a key event in the development of diabetic complications. Interestingly, some common aspects exist between hyperglycemia and hypoxia-induced phenomena. Thus, hyperglycemia may induce cellular hypoxia, and this phenomenon may also be involved in the pathogenesis of diabetic complications. In endothelial cells (ECs), cellular hypoxia increased after incubation with high glucose (HG). A similar phenomenon was observed in glomeruli of diabetic mice. HG-induced cellular hypoxia was suppressed by mitochondria blockades or manganese superoxide dismutase (MnSOD) overexpression, which is a specific SOD for mtROS. Overexpression of MnSOD also increased the expression of aquaporin-1 (AQP1), a water and oxygen channel. AQP1 overexpression in ECs suppressed hyperglycemia-induced cellular hypoxia, endothelin-1 and fibronectin overproduction, and apoptosis. Therefore, hyperglycemia-induced cellular hypoxia and mtROS generation may promote hyperglycemic damage in a coordinated manner. PMID:27383386

  3. Hippocampal ensemble dynamics timestamp events in long-term memory.

    PubMed

    Rubin, Alon; Geva, Nitzan; Sheintuch, Liron; Ziv, Yaniv

    2015-01-01

    The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. PMID:26682652

  4. Cellular Reflectarray Antenna

    NASA Technical Reports Server (NTRS)

    Romanofsky, Robert R.

    2010-01-01

    The cellular reflectarray antenna is intended to replace conventional parabolic reflectors that must be physically aligned with a particular satellite in geostationary orbit. These arrays are designed for specified geographical locations, defined by latitude and longitude, each called a "cell." A particular cell occupies nominally 1,500 square miles (3,885 sq. km), but this varies according to latitude and longitude. The cellular reflectarray antenna designed for a particular cell is simply positioned to align with magnetic North, and the antenna surface is level (parallel to the ground). A given cellular reflectarray antenna will not operate in any other cell.

  5. CELLULAR MAGNESIUM HOMEOSTASIS

    PubMed Central

    Romani, Andrea M.P.

    2011-01-01

    Magnesium, the second most abundant cellular cation after potassium, is essential to regulate numerous cellular functions and enzymes, including ion channels, metabolic cycles, and signaling pathways, as attested by more than 1000 entries in the literature. Despite significant recent progress, however, our understanding of how cells regulate Mg2+ homeostasis and transport still remains incomplete. For example, the occurrence of major fluxes of Mg2+ in either direction across the plasma membrane of mammalian cells following metabolic or hormonal stimuli has been extensively documented. Yet, the mechanisms ultimately responsible for magnesium extrusion across the cell membrane have not been cloned. Even less is known about the regulation in cellular organelles. The present review is aimed at providing the reader with a comprehensive and up-to-date understanding of the mechanisms enacted by eukaryotic cells to regulate cellular Mg2+ homeostasis and how these mechanisms are altered under specific pathological conditions. PMID:21640700

  6. Recent Advances in Cellular Glycomic Analyses

    PubMed Central

    Furukawa, Jun-ichi; Fujitani, Naoki; Shinohara, Yasuro

    2013-01-01

    A large variety of glycans is intricately located on the cell surface, and the overall profile (the glycome, given the entire repertoire of glycoconjugate-associated sugars in cells and tissues) is believed to be crucial for the diverse roles of glycans, which are mediated by specific interactions that control cell-cell adhesion, immune response, microbial pathogenesis and other cellular events. The glycomic profile also reflects cellular alterations, such as development, differentiation and cancerous change. A glycoconjugate-based approach would therefore be expected to streamline discovery of novel cellular biomarkers. Development of such an approach has proven challenging, due to the technical difficulties associated with the analysis of various types of cellular glycomes; however, recent progress in the development of analytical methodologies and strategies has begun to clarify the cellular glycomics of various classes of glycoconjugates. This review focuses on recent advances in the technical aspects of cellular glycomic analyses of major classes of glycoconjugates, including N- and O-linked glycans, derived from glycoproteins, proteoglycans and glycosphingolipids. Articles that unveil the glycomics of various biologically important cells, including embryonic and somatic stem cells, induced pluripotent stem (iPS) cells and cancer cells, are discussed. PMID:24970165

  7. Event Perception

    PubMed Central

    Radvansky, Gabriel; Zacks, Jeffrey M.

    2012-01-01

    Events are central elements of human experience. Formally, they can be individuated in terms of the entities that compose them, the features of those entities, and the relations amongst entities. Psychologically, representations of events capture their spatiotemporal location, the people and objects involved, and the relations between these elements. Here, we present an account of the nature of psychological representations of events and how they are constructed and updated. Event representations are like images in that they are isomorphic to the situations they represent. However, they are like models or language in that they are constructed of components rather than being holistic. Also, they are partial representations that leave out some elements and abstract others. Representations of individual events are informed by schematic knowledge about general classes of events. Event representations are constructed in a process that segments continuous activity into discrete events. The construction of a series of event representations forms a basis for predicting the future, planning for that future, and imagining alternatives. PMID:23082236

  8. Unveiling the principle of microRNA-mediated redundancy in cellular pathway regulation

    PubMed Central

    Fischer, Simon; Handrick, René; Aschrafi, Armaz; Otte, Kerstin

    2015-01-01

    Understanding the multifaceted nature of microRNA (miRNA) function in mammalian cells is still a challenge. Commonly accepted principles of cooperativity and multiplicity of miRNA function imply that individual mRNAs can be targeted by several miRNAs whereas a single miRNA may concomitantly regulate a subset of different genes. However, there is a paucity of information whether multiple miRNAs regulate critical cellular events and thereby acting redundantly. To gain insight into this notion, we conducted an unbiased high-content miRNA screen by individually introducing 1139 miRNA mimics into Chinese hamster ovary (CHO) cells. We discovered that 66% of all miRNAs significantly impacted on proliferation, protein expression, apoptosis and necrosis. In summary, we provide evidence for a substantial degree of redundancy among miRNAs to maintain cellular homeostasis. PMID:25826657

  9. Irregular Cellular Learning Automata.

    PubMed

    Esnaashari, Mehdi; Meybodi, Mohammad Reza

    2015-08-01

    Cellular learning automaton (CLA) is a recently introduced model that combines cellular automaton (CA) and learning automaton (LA). The basic idea of CLA is to use LA to adjust the state transition probability of stochastic CA. This model has been used to solve problems in areas such as channel assignment in cellular networks, call admission control, image processing, and very large scale integration placement. In this paper, an extension of CLA called irregular CLA (ICLA) is introduced. This extension is obtained by removing the structure regularity assumption in CLA. Irregularity in the structure of ICLA is needed in some applications, such as computer networks, web mining, and grid computing. The concept of expediency has been introduced for ICLA and then, conditions under which an ICLA becomes expedient are analytically found. PMID:25291810

  10. Natural Agents: Cellular and Molecular Mechanisms of Photoprotection

    PubMed Central

    Afaq, Farrukh

    2010-01-01

    The skin is the largest organ of the body that produces a flexible and self-repairing barrier and protects the body from most common potentially harmful physical, environmental, and biological insults. Solar ultraviolet (UV) radiation is one of the major environmental insults to the skin and causes multi-tiered cellular and molecular events eventually leading to skin cancer. The past decade has seen a surge in the incidence of skin cancer due to changes in life style patterns that have led to a significant increase in the amount of UV radiation that people receive. Reducing excessive exposure to UV radiation is desirable; nevertheless this approach is not easy to implement. Therefore, there is an urgent need to develop novel strategies to reduce the adverse biological effects of UV radiation on the skin. A wide variety of natural agents have been reported to possess substantial skin photoprotective effects. Numerous preclinical and clinical studies have elucidated that natural agents act by several cellular and molecular mechanisms to delay or prevent skin cancer. In this review article, we have summarized and discussed some of the selected natural agents for skin photoprotection. PMID:21147060

  11. Cellular reprogramming and hepatocellular carcinoma development.

    PubMed

    Zheng, Yun-Wen; Nie, Yun-Zhong; Taniguchi, Hideki

    2013-12-21

    Hepatocellular carcinoma (HCC) is one of the most common cancers, and is also the leading cause of death worldwide. Studies have shown that cellular reprogramming contributes to chemotherapy and/or radiotherapy resistance and the recurrence of cancers. In this article, we summarize and discuss the latest findings in the area of cellular reprogramming in HCC. The aberrant expression of transcription factors OCT4, KLF4, SOX2, c-MYC, NANOG, and LIN28 have been also observed, and the expression of these transcription factors is associated with unfavorable clinical outcomes in HCC. Studies indicate that cellular reprogramming may play a critical role in the occurrence and recurrence of HCC. Recent reports have shown that DNA methylation, miRNAs, tumor microenvironment, and signaling pathways can induce the expression of stemness transcription factors, which leads to cellular reprogramming in HCC. Furthermore, studies indicate that therapies based on cellular reprogramming could revolutionize HCC treatment. Finally, a novel therapeutic concept is discussed: reprogramming control therapy. A potential reprogramming control therapy method could be developed based on the reprogramming demonstrated in HCC studies and applied at two opposing levels: differentiation and reprogramming. Our increasing understanding and control of cellular programming should facilitate the exploitation of this novel therapeutic concept and its application in clinical HCC treatment, which may represent a promising strategy in the future that is not restricted to liver cancer. PMID:24379607

  12. The common ancestry of life

    PubMed Central

    2010-01-01

    Background It is common belief that all cellular life forms on earth have a common origin. This view is supported by the universality of the genetic code and the universal conservation of multiple genes, particularly those that encode key components of the translation system. A remarkable recent study claims to provide a formal, homology independent test of the Universal Common Ancestry hypothesis by comparing the ability of a common-ancestry model and a multiple-ancestry model to predict sequences of universally conserved proteins. Results We devised a computational experiment on a concatenated alignment of universally conserved proteins which shows that the purported demonstration of the universal common ancestry is a trivial consequence of significant sequence similarity between the analyzed proteins. The nature and origin of this similarity are irrelevant for the prediction of "common ancestry" of by the model-comparison approach. Thus, homology (common origin) of the compared proteins remains an inference from sequence similarity rather than an independent property demonstrated by the likelihood analysis. Conclusion A formal demonstration of the Universal Common Ancestry hypothesis has not been achieved and is unlikely to be feasible in principle. Nevertheless, the evidence in support of this hypothesis provided by comparative genomics is overwhelming. Reviewers this article was reviewed by William Martin, Ivan Iossifov (nominated by Andrey Rzhetsky) and Arcady Mushegian. For the complete reviews, see the Reviewers' Report section. PMID:21087490

  13. Reprogramming cellular events by poly(ADP-ribose)-binding proteins

    PubMed Central

    Pic, Émilie; Ethier, Chantal; Dawson, Ted M.; Dawson, Valina L.; Masson, Jean-Yves; Poirier, Guy G.; Gagné, Jean-Philippe

    2013-01-01

    Poly(ADP-ribosyl)ation is a posttranslational modification catalyzed by the poly(ADP-ribose) polymerases (PARPs). These enzymes covalently modify glutamic, aspartic and lysine amino acid side chains of acceptor proteins by the sequential addition of ADP-ribose (ADPr) units. The poly(ADP-ribose) (pADPr) polymers formed alter the physico-chemical characteristics of the substrate with functional consequences on its biological activities. Recently, non-covalent binding to pADPr has emerged as a key mechanism to modulate and coordinate several intracellular pathways including the DNA damage response, protein stability and cell death. In this review, we describe the basis of non-covalent binding to pADPr that has led to the emerging concept of pADPr-responsive signaling pathways. This review emphasizes the structural elements and the modular strategies developed by pADPr-binding proteins to exert a fine-tuned control of a variety of pathways. Poly(ADP-ribosyl)ation reactions are highly regulated processes, both spatially and temporally, for which at least four specialized pADPr-binding modules accommodate different pADPr structures and reprogram protein functions. In this review, we highlight the role of well-characterized and newly discovered pADPr-binding modules in a diverse set of physiological functions. PMID:23268355

  14. Genetic Dominance & Cellular Processes

    ERIC Educational Resources Information Center

    Seager, Robert D.

    2014-01-01

    In learning genetics, many students misunderstand and misinterpret what "dominance" means. Understanding is easier if students realize that dominance is not a mechanism, but rather a consequence of underlying cellular processes. For example, metabolic pathways are often little affected by changes in enzyme concentration. This means that…

  15. Teaching cellular engineering.

    PubMed

    Hammer, Daniel A; Waugh, Richard E

    2006-02-01

    Cellular engineering is one of the fastest growing subdisciplines in the field of Biomedical Engineering. It involves the application of engineering analysis to understand and control cellular behavior, with the ultimate objective of developing novel therapeutic or diagnostic approaches for the clinic or harnessing cellular function for commercial applications. Well-educated students in this area need strong foundational knowledge in engineering science, chemistry, and cell and molecular biology. In undergraduate curricula, the challenge is to include essential engineering skills plus appropriate levels of training in chemistry and biology while satisfying accreditation-mandated breadth in engineering training. At the graduate level, educators must accommodate students with diverse backgrounds and provide them with both a state-of-the-art understanding of the life sciences and the most advanced engineering skills. Engineering curricular content should include mechanics and materials, physical chemistry, transport phenomena, and control theory. Training from faculty with appointments and research programs in the life sciences is generally recommended, and additional life science content should also be integrated within the engineering curriculum. A capstone course in cellular engineering that includes opportunities for students to have hands-on experiences with state-of-the-art laboratory techniques is highly recommended. PMID:16450196

  16. Auxin and Cellular Elongation.

    PubMed

    Velasquez, Silvia Melina; Barbez, Elke; Kleine-Vehn, Jürgen; Estevez, José M

    2016-03-01

    Auxin is a crucial growth regulator in plants. However, a comprehensive understanding of how auxin induces cell expansion is perplexing, because auxin acts in a concentration- and cell type-dependent manner. Consequently, it is desirable to focus on certain cell types to exemplify the underlying growth mechanisms. On the other hand, plant tissues display supracellular growth (beyond the level of single cells); hence, other cell types might compromise the growth of a certain tissue. Tip-growing cells do not display neighbor-induced growth constraints and, therefore, are a valuable source of information for growth-controlling mechanisms. Here, we focus on auxin-induced cellular elongation in root hairs, exposing a mechanistic view of plant growth regulation. We highlight a complex interplay between auxin metabolism and transport, steering root hair development in response to internal and external triggers. Auxin signaling modules and downstream cascades of transcription factors define a developmental program that appears rate limiting for cellular growth. With this knowledge in mind, the root hair cell is a very suitable model system in which to dissect cellular effectors required for cellular expansion. PMID:26787325

  17. The New Cellular Immunology

    ERIC Educational Resources Information Center

    Claman, Henry N.

    1973-01-01

    Discusses the nature of the immune response and traces many of the discoveries that have led to the present state of knowledge in immunology. The new cellular immunology is directing its efforts toward improving health by proper manipulation of the immune mechanisms of the body. (JR)

  18. [Cellular pathology of neurodegenerative disorders].

    PubMed

    Wakabayashi, Koichi

    2013-01-01

    Common cellular and molecular mechanisms including protein aggregation and inclusion body formation are involved in many neurodegenerative diseases. α-Synuclein is a major component of Lewy bodies in Parkinson's disease (PD) as well as in glial cytoplasmic inclusions in multiple system atrophy (MSA). Tau is a principal component of neurofibrillary and glial tangles in tauopathies. Recently, TDP-43 was identified as a component of ubiquitinated inclusions in amyotrophic lateral sclerosis and frontotemporal lobar degeneration. PD is traditionally considered a movement disorder with hallmark lesions in the brainstem pigmented nuclei. However, pathological changes occur in widespread regions of the central and peripheral nervous systems in this disease. Furthermore, primary glial involvement ("gliodegeneration") can be observed in PD and MSA as well as in tauopathy. The present article reviews abnormal protein accumulation and inclusion body formation inside and outside the central nervous system. PMID:23965852

  19. Regulation of cellular chromatin state

    PubMed Central

    Mishra, Rakesh K; Dhawan, Jyotsna

    2010-01-01

    The identity and functionality of eukaryotic cells is defined not just by their genomic sequence which remains constant between cell types, but by their gene expression profiles governed by epigenetic mechanisms. Epigenetic controls maintain and change the chromatin state throughout development, as exemplified by the setting up of cellular memory for the regulation and maintenance of homeotic genes in proliferating progenitors during embryonic development. Higher order chromatin structure in reversibly arrested adult stem cells also involves epigenetic regulation and in this review we highlight common trends governing chromatin states, focusing on quiescence and differentiation during myogenesis. Together, these diverse developmental modules reveal the dynamic nature of chromatin regulation providing fresh insights into the role of epigenetic mechanisms in potentiating development and differentiation. PMID:20592864

  20. Cellular compartmentalization of secondary metabolism

    PubMed Central

    Kistler, H. Corby; Broz, Karen

    2015-01-01

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

  1. Pelvic Retroperitoneal Cellular Leiomyoma: A Case Report.

    PubMed

    Tantitamit, Tanitra; Hamontri, Suttha; Rangsiratanakul, Likit; Suksamarnwong, Maysita

    2015-10-01

    Leiomyomas are common benign gynecological tumors and usually arise in the uterus. The retroperitoneal cellular leiomyoma, one of the unusual manifestations, is a rare tumor. Diagnosis and treatment are challenges. We report a case of 65-year-old women presented with an asymptomatic mass beneath the right posterior vaginal mucosa. CT imaging revealed heterogeneous mass 6 cm in the pelvic cavity abutted lower segment of uterus, cervix, and vagina. The provisional diagnosis was subserosal cervical leiomyoma. She underwent exploratory laparotomy. Intra-operative, a normal size uterus was found separately from retroperitoneal pelvic mass at the level of internal os. Histological report confirmed cellular leiomyoma later Total hysterectomy, bilateral salpingoophorectomy and completely excision of tumor were achieved with good outcome. Our patient represents the rare case of retroperitoneal cellular leiomyoma, which is hardly identified from internal examination and preoperative imaging. Surgical removal is essential for pathological diagnosis and treatment. PMID:26817226

  2. COMMON ENVELOPE: ENTHALPY CONSIDERATION

    SciTech Connect

    Ivanova, N.; Chaichenets, S.

    2011-04-20

    In this Letter, we discuss a modification to the criterion for the common envelope (CE) event to result in envelope dispersion. We emphasize that the current energy criterion for the CE phase is not sufficient for an instability of the CE, nor for an ejection. However, in some cases, stellar envelopes undergo stationary mass outflows, which are likely to occur during the slow spiral-in stage of the CE event. We propose the condition for such outflows, in a manner similar to the currently standard {alpha}{sub CE}{lambda}-prescription but with an addition of P/{rho} term in the energy balance equation, accounting therefore for the enthalpy of the envelope rather than merely the gas internal energy. This produces a significant correction, which might help to dispense with an unphysically high value of energy efficiency parameter during the CE phase, currently required in the binary population synthesis studies to make the production of low-mass X-ray binaries with a black hole companion to match the observations.

  3. Ectopic endometrium in human foetuses is a common event and sustains the theory of müllerianosis in the pathogenesis of endometriosis, a disease that predisposes to cancer

    PubMed Central

    Signorile, Pietro G; Baldi, Feliciano; Bussani, Rossana; D'Armiento, Mariarosaria; De Falco, Maria; Baldi, Alfonso

    2009-01-01

    Background Endometriosis is a gynecological disease defined by the histological presence of endometrial glands and stroma outside the uterine cavity. Women with endometriosis have an increased risk of different types of malignancies, especially ovarian cancer and non-Hodgkin's lymphoma. Though there are several theories, researchers remain unsure as to the definitive cause of endometriosis. Our objective was to test the validity of the theory of müllerianosis for endometriosis, that is the misplacing of primitive endometrial tissue along the migratory pathway of foetal organogenesis Methods We have collected at autopsy 36 human female foetuses at different gestational age. We have performed a morphological and immunohistochemical study (expression of oestrogen receptor and CA125) on the pelvic organs of the 36 foetuses included en-block and totally analyzed. Results In 4 out of 36 foetuses we found presence of misplaced endometrium in five different ectopic sites: in the recto-vaginal septum, in the proximity of the Douglas pouch, in the mesenchimal tissue close to the posterior wall of the uterus, in the rectal tube at the level of muscularis propria, and in the wall of the uterus. All these sites are common location of endometriosis in women. Conclusion We propose that a cause of endometriosis is the dislocation of primitive endometrial tissue outside the uterine cavity during organogenesis. PMID:19358700

  4. Cellular growth in biofilms

    SciTech Connect

    Wood, B.D.; Whitaker, S.

    1999-09-20

    In this paper the authors develop a macroscopic evolutionary equation for the growth of the cellular phase starting from a microscopic description of mass transport and a simple structured model for product formation. The methods of continuum mechanics and volume averaging are used to develop the macroscopic representation by carefully considering the fluxes of chemical species that pertain to cell growth. The concept of structured models is extended to include the transport of reacting chemical species at the microscopic scale. The resulting macroscopic growth model is similar in form to previously published models for the transport of a single substrate and electron donor and for the production of cellular mass and exopolymer. The method of volume averaging indicated under what conditions the developed growth model is valid and provides an explicit connection between the relevant microscopic model parameters and their corresponding macroscopic counterparts.

  5. Transcriptomic responses to darkness stress point to common coral bleaching mechanisms

    NASA Astrophysics Data System (ADS)

    Desalvo, M. K.; Estrada, A.; Sunagawa, S.; Medina, Mónica

    2012-03-01

    Coral bleaching occurs in response to numerous abiotic stressors, the ecologically most relevant of which is hyperthermic stress due to increasing seawater temperatures. Bleaching events can span large geographic areas and are currently a salient threat to coral reefs worldwide. Much effort has been focused on understanding the molecular and cellular events underlying bleaching, and these studies have mainly utilized heat and light stress regimes. In an effort to determine whether different stressors share common bleaching mechanisms, we used complementary DNA (cDNA) microarrays for the corals Acropora palmata and Montastraea faveolata (containing >10,000 features) to measure differential gene expression during darkness stress. Our results reveal a striking transcriptomic response to darkness in A. palmata involving chaperone and antioxidant up-regulation, growth arrest, and metabolic modifications. As these responses were previously measured during thermal stress, our results suggest that different stressors may share common bleaching mechanisms. Furthermore, our results point to hypoxia and endoplasmic reticulum stress as critical cellular events involved in molecular bleaching mechanisms. On the other hand, we identified a meager transcriptomic response to darkness in M. faveolata where gene expression differences between host colonies and sampling locations were greater than differences between control and stressed fragments. This and previous coral microarray studies reveal the immense range of transcriptomic responses that are possible when studying two coral species that differ greatly in their ecophysiology, thus pointing to the importance of comparative approaches in forecasting how corals will respond to future environmental change.

  6. Cellular dysfunction in sepsis.

    PubMed

    Singer, Mervyn

    2008-12-01

    Cellular dysfunction is a commonplace sequelum of sepsis and other systemic inflammatory conditions. Impaired energy production (related to mitochondrial inhibition, damage, and reduced protein turnover) appears to be a core mechanism underlying the development of organ dysfunction. The reduction in energy availability appears to trigger a metabolic shutdown that impairs normal functioning of the cell. This may well represent an adaptive mechanism analogous to hibernation that prevents a massive degree of cell death and thus enables eventual recovery in survivors. PMID:18954700

  7. Radiolabeled cellular blood elements

    SciTech Connect

    Thakur, M.L.; Ezikowitz, M.D.; Hardeman, M.R.

    1985-01-01

    This book contains papers delivered by guest lectures and participants at the Advanced Study Institute's colloquium on Radiolabeled Cellular Blood Elements at Maratea, Italy on August 29, to September 9, 1982. The book includes chapters on basic cell physiology and critical reviews of data and experience in the preparation and use of radiolabeled cells, as well as reports on very recent developments, from a faculty that included experts on cell physiology in health and disease and on the technology of in vivo labeling.

  8. Predictability in cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Chira, Camelia; Giuclea, Marius

    2014-01-01

    Modelled as finite homogeneous Markov chains, probabilistic cellular automata with local transition probabilities in (0, 1) always posses a stationary distribution. This result alone is not very helpful when it comes to predicting the final configuration; one needs also a formula connecting the probabilities in the stationary distribution to some intrinsic feature of the lattice configuration. Previous results on the asynchronous cellular automata have showed that such feature really exists. It is the number of zero-one borders within the automaton's binary configuration. An exponential formula in the number of zero-one borders has been proved for the 1-D, 2-D and 3-D asynchronous automata with neighborhood three, five and seven, respectively. We perform computer experiments on a synchronous cellular automaton to check whether the empirical distribution obeys also that theoretical formula. The numerical results indicate a perfect fit for neighbourhood three and five, which opens the way for a rigorous proof of the formula in this new, synchronous case. PMID:25271778

  9. Probabilistic cellular automata.

    PubMed

    Agapie, Alexandru; Andreica, Anca; Giuclea, Marius

    2014-09-01

    Cellular automata are binary lattices used for modeling complex dynamical systems. The automaton evolves iteratively from one configuration to another, using some local transition rule based on the number of ones in the neighborhood of each cell. With respect to the number of cells allowed to change per iteration, we speak of either synchronous or asynchronous automata. If randomness is involved to some degree in the transition rule, we speak of probabilistic automata, otherwise they are called deterministic. With either type of cellular automaton we are dealing with, the main theoretical challenge stays the same: starting from an arbitrary initial configuration, predict (with highest accuracy) the end configuration. If the automaton is deterministic, the outcome simplifies to one of two configurations, all zeros or all ones. If the automaton is probabilistic, the whole process is modeled by a finite homogeneous Markov chain, and the outcome is the corresponding stationary distribution. Based on our previous results for the asynchronous case-connecting the probability of a configuration in the stationary distribution to its number of zero-one borders-the article offers both numerical and theoretical insight into the long-term behavior of synchronous cellular automata. PMID:24999557

  10. Quantum cellular automata

    NASA Astrophysics Data System (ADS)

    Porod, Wolfgang; Lent, Craig S.; Bernstein, Gary H.

    1994-06-01

    The Notre Dame group has developed a new paradigm for ultra-dense and ultra-fast information processing in nanoelectronic systems. These Quantum Cellular Automata (QCA's) are the first concrete proposal for a technology based on arrays of coupled quantum dots. The basic building block of these cellular arrays is the Notre Dame Logic Cell, as it has been called in the literature. The phenomenon of Coulomb exclusion, which is a synergistic interplay of quantum confinement and Coulomb interaction, leads to a bistable behavior of each cell which makes possible their use in large-scale cellular arrays. The physical interaction between neighboring cells has been exploited to implement logic functions. New functionality may be achieved in this fashion, and the Notre Dame group invented a versatile majority logic gate. In a series of papers, the feasibility of QCA wires, wire crossing, inverters, and Boolean logic gates was demonstrated. A major finding is that all logic functions may be integrated in a hierarchial fashion which allows the design of complicated QCA structures. The most complicated system which was simulated to date is a one-bit full adder consisting of some 200 cells. In addition to exploring these new concepts, efforts are under way to physically realize such structures both in semiconductor and metal systems. Extensive modeling work of semiconductor quantum dot structures has helped identify optimum design parameters for QCA experimental implementations.

  11. Cellular ubiquitin pool dynamics and homeostasis

    PubMed Central

    Ryu, Kwon-Yul

    2014-01-01

    Ubiquitin (Ub) is a versatile signaling molecule that plays important roles in a variety of cellular processes. Cellular Ub pools, which are composed of free Ub and Ub conjugates, are in dynamic equilibrium inside cells. In particular, increasing evidence suggests that Ub homeostasis, or the maintenance of free Ub above certain threshold levels, is important for cellular function and survival under normal or stress conditions. Accurate determination of various Ub species, including levels of free Ub and specific Ub chain linkages, have become possible in biological specimens as a result of the introduction of the proteomic approach using mass spectrometry. This technology has facilitated research on dynamic properties of cellular Ub pools and has provided tools for in-depth investigation of Ub homeostasis. In this review, we have also discussed the consequences of the disruption of Ub pool dynamics and homeostasis via deletion of polyubiquitin genes or mutations of deubiquitinating enzymes. The common consequence was a reduced availability of free Ub and a significant impact on the function and viability of cells. These observations further indicate that the levels of free Ub are important determinants for cellular protection. [BMB Reports 2014; 47(9): 475-482] PMID:24924398

  12. Cellular Mechanisms of Somatic Stem Cell Aging

    PubMed Central

    Jung, Yunjoon

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  13. Cellular mechanisms of somatic stem cell aging.

    PubMed

    Jung, Yunjoon; Brack, Andrew S

    2014-01-01

    Tissue homeostasis and regenerative capacity rely on rare populations of somatic stem cells endowed with the potential to self-renew and differentiate. During aging, many tissues show a decline in regenerative potential coupled with a loss of stem cell function. Cells including somatic stem cells have evolved a series of checks and balances to sense and repair cellular damage to maximize tissue function. However, during aging the mechanisms that protect normal cell function begin to fail. In this review, we will discuss how common cellular mechanisms that maintain tissue fidelity and organismal lifespan impact somatic stem cell function. We will highlight context-dependent changes and commonalities that define aging, by focusing on three age-sensitive stem cell compartments: blood, neural, and muscle. Understanding the interaction between extrinsic regulators and intrinsic effectors that operate within different stem cell compartments is likely to have important implications for identifying strategies to improve health span and treat age-related degenerative diseases. PMID:24439814

  14. A scientific role for Space Station Freedom: Research at the cellular level

    NASA Technical Reports Server (NTRS)

    Johnson, Terry C.; Brady, John N.

    1993-01-01

    The scientific importance of Space Station Freedom is discussed in light of the valuable information that can be gained in cellular and developmental biology with regard to the microgravity environment on the cellular cytoskeleton, cellular responses to extracellular signal molecules, morphology, events associated with cell division, and cellular physiology. Examples of studies in basic cell biology, as well as their potential importance to concerns for future enabling strategies, are presented.

  15. No Common Opinion on the Common Core

    ERIC Educational Resources Information Center

    Henderson, Michael B.; Peterson, Paul E.; West, Martin R.

    2015-01-01

    According to the three authors of this article, the 2014 "EdNext" poll yields four especially important new findings: (1) Opinion with respect to the Common Core has yet to coalesce. The idea of a common set of standards across the country has wide appeal, and the Common Core itself still commands the support of a majority of the public.…

  16. Formin’ cellular structures

    PubMed Central

    Bogdan, Sven; Schultz, Jörg; Grosshans, Jörg

    2014-01-01

    Members of the Diaphanous (Dia) protein family are key regulators of fundamental actin driven cellular processes, which are conserved from yeast to humans. Researchers have uncovered diverse physiological roles in cell morphology, cell motility, cell polarity, and cell division, which are involved in shaping cells into tissues and organs. The identification of numerous binding partners led to substantial progress in our understanding of the differential functions of Dia proteins. Genetic approaches and new microscopy techniques allow important new insights into their localization, activity, and molecular principles of regulation. PMID:24719676

  17. Control of cellular automata

    NASA Astrophysics Data System (ADS)

    Bagnoli, Franco; Rechtman, Raúl; El Yacoubi, Samira

    2012-12-01

    We study the problem of master-slave synchronization and control of totalistic cellular automata. The synchronization mechanism is that of setting a fraction of sites of the slave system equal to those of the master one (pinching synchronization). The synchronization observable is the distance between the two configurations. We present three control strategies that exploit local information (the number of nonzero first-order Boolean derivatives) in order to choose the sites to be synchronized. When no local information is used, we speak of simple pinching synchronization. We find the critical properties of control and discuss the best control strategy compared with simple synchronization.

  18. Cellular mechanics and motility

    NASA Astrophysics Data System (ADS)

    Hénon, Sylvie; Sykes, Cécile

    2015-10-01

    The term motility defines the movement of a living organism. One widely known example is the motility of sperm cells, or the one of flagellar bacteria. The propulsive element of such organisms is a cilium(or flagellum) that beats. Although cells in our tissues do not have a flagellum in general, they are still able to move, as we will discover in this chapter. In fact, in both cases of movement, with or without a flagellum, cell motility is due to a dynamic re-arrangement of polymers inside the cell. Let us first have a closer look at the propulsion mechanism in the case of a flagellum or a cilium, which is the best known, but also the simplest, and which will help us to define the hydrodynamic general conditions of cell movement. A flagellum is sustained by cellular polymers arranged in semi-flexible bundles and flagellar beating generates cell displacement. These polymers or filaments are part of the cellular skeleton, or "cytoskeleton", which is, in this case, external to the cellular main body of the organism. In fact, bacteria move in a hydrodynamic regime in which viscosity dominates over inertia. The system is thus in a hydrodynamic regime of low Reynolds number (Box 5.1), which is nearly exclusively the case in all cell movements. Bacteria and their propulsion mode by flagella beating are our unicellular ancestors 3.5 billion years ago. Since then, we have evolved to form pluricellular organisms. However, to keep the ability of displacement, to heal our wounds for example, our cells lost their flagellum, since it was not optimal in a dense cell environment: cells are too close to each other to leave enough space for the flagella to accomplish propulsion. The cytoskeleton thus developed inside the cell body to ensure cell shape changes and movement, and also mechanical strength within a tissue. The cytoskeleton of our cells, like the polymers or filaments that sustain the flagellum, is also composed of semi-flexible filaments arranged in bundles, and also in

  19. Cellular Mechanisms Controlling Caspase Activation and Function

    PubMed Central

    Parrish, Amanda B.; Freel, Christopher D.; Kornbluth, Sally

    2013-01-01

    Caspases are the primary drivers of apoptotic cell death, cleaving cellular proteins that are critical for dismantling the dying cell. Initially translated as inactive zymogenic precursors, caspases are activated in response to a variety of cell death stimuli. In addition to factors required for their direct activation (e.g., dimerizing adaptor proteins in the case of initiator caspases that lie at the apex of apoptotic signaling cascades), caspases are regulated by a variety of cellular factors in a myriad of physiological and pathological settings. For example, caspases may be modified posttranslationally (e.g., by phosphorylation or ubiquitylation) or through interaction of modulatory factors with either the zymogenic or active form of a caspase, altering its activation and/or activity. These regulatory events may inhibit or enhance enzymatic activity or may affect activity toward particular cellular substrates. Finally, there is emerging literature to suggest that caspases can participate in a variety of cellular processes unrelated to apoptotic cell death. In these settings, it is particularly important that caspases are maintained under stringent control to avoid inadvertent cell death. It is likely that continued examination of these processes will reveal new mechanisms of caspase regulation with implications well beyond control of apoptotic cell death. PMID:23732469

  20. Monte Carlo Event Generators

    NASA Astrophysics Data System (ADS)

    Dytman, Steven

    2011-10-01

    Every neutrino experiment requires a Monte Carlo event generator for various purposes. Historically, each series of experiments developed their own code which tuned to their needs. Modern experiments would benefit from a universal code (e.g. PYTHIA) which would allow more direct comparison between experiments. GENIE attempts to be that code. This paper compares most commonly used codes and provides some details of GENIE.

  1. Extreme Events

    NASA Astrophysics Data System (ADS)

    Nott, Jonathan

    2006-04-01

    The assessment of risks posed by natural hazards such as floods, droughts, earthquakes, tsunamis or cyclones, is often based on short-term historical records that may not reflect the full range or magnitude of events possible. As human populations grow, especially in hazard-prone areas, methods for accurately assessing natural hazard risks are becoming increasingly important. In Extreme Events Jonathan Nott describes the many methods used to reconstruct such hazards from natural long-term records. He demonstrates how long-term (multi-century to millennial) records are essential in gaining a realistic understanding of the variability of natural hazards, and how short-term historical records can often misrepresent the likely risks associated with natural hazards. This book will form a useful resource for students taking courses covering natural hazards and risk assessment. It will also be valuable for urban planners, policy makers and non-specialists as a guide to understanding and reconstructing long-term records of natural hazards. Explains mechanisms that cause extreme events and discusses their prehistoric records Describes how to reconstruct long-term records of natural hazards in order to make accurate risk assessments Demonstrates that natural hazards can follow cycles over time and do not occur randomly

  2. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA...

  3. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA...

  4. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA...

  5. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA...

  6. 47 CFR 22.969 - Cellular RSA licenses subject to competitive bidding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular RSA licenses subject to competitive bidding. 22.969 Section 22.969 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.969 Cellular RSA...

  7. Cellular Contraction and Polarization Drive Collective Cellular Motion.

    PubMed

    Notbohm, Jacob; Banerjee, Shiladitya; Utuje, Kazage J C; Gweon, Bomi; Jang, Hwanseok; Park, Yongdoo; Shin, Jennifer; Butler, James P; Fredberg, Jeffrey J; Marchetti, M Cristina

    2016-06-21

    Coordinated motions of close-packed multicellular systems typically generate cooperative packs, swirls, and clusters. These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate collective cellular motion remain poorly understood. Here, we study forces and motions in a confined epithelial monolayer and make two experimental observations: 1) the direction of local cellular motion deviates systematically from the direction of the local traction exerted by each cell upon its substrate; and 2) oscillating waves of cellular motion arise spontaneously. Based on these observations, we propose a theory that connects forces and motions using two internal state variables, one of which generates an effective cellular polarization, and the other, through contractile forces, an effective cellular inertia. In agreement with theoretical predictions, drugs that inhibit contractility reduce both the cellular effective elastic modulus and the frequency of oscillations. Together, theory and experiment provide evidence suggesting that collective cellular motion is driven by at least two internal variables that serve to sustain waves and to polarize local cellular traction in a direction that deviates systematically from local cellular velocity. PMID:27332131

  8. Integrated cellular systems

    NASA Astrophysics Data System (ADS)

    Harper, Jason C.

    The generation of new three-dimensional (3D) matrices that enable integration of biomolecular components and whole cells into device architectures, without adversely altering their morphology or activity, continues to be an expanding and challenging field of research. This research is driven by the promise that encapsulated biomolecules and cells can significantly impact areas as diverse as biocatalysis, controlled delivery of therapeutics, environmental and industrial process monitoring, early warning of warfare agents, bioelectronics, photonics, smart prosthetics, advanced physiological sensors, portable medical diagnostic devices, and tissue/organ replacement. This work focuses on the development of a fundamental understanding of the biochemical and nanomaterial mechanisms that govern the cell directed assembly and integration process. It was shown that this integration process relies on the ability of cells to actively develop a pH gradient in response to evaporation induced osmotic stress, which catalyzes silica condensation within a thin 3D volume surrounding the cells, creating a functional bio/nano interface. The mechanism responsible for introducing functional foreign membrane-bound proteins via proteoliposome addition to the silica-lipid-cell matrix was also determined. Utilizing this new understanding, 3D cellular immobilization capabilities were extended using sol-gel matrices endowed with glycerol, trehalose, and media components. The effects of these additives, and the metabolic phase of encapsulated S. cerivisiase cells, on long-term viability and the rate of inducible gene expression was studied. This enabled the entrapment of cells within a novel microfluidic platform capable of simultaneous colorimetric, fluorescent, and electrochemical detection of a single analyte, significantly improving confidence in the biosensor output. As a complementary approach, multiphoton protein lithography was utilized to engineer 3D protein matrices in which to

  9. Engineering Cellular Metabolism.

    PubMed

    Nielsen, Jens; Keasling, Jay D

    2016-03-10

    Metabolic engineering is the science of rewiring the metabolism of cells to enhance production of native metabolites or to endow cells with the ability to produce new products. The potential applications of such efforts are wide ranging, including the generation of fuels, chemicals, foods, feeds, and pharmaceuticals. However, making cells into efficient factories is challenging because cells have evolved robust metabolic networks with hard-wired, tightly regulated lines of communication between molecular pathways that resist efforts to divert resources. Here, we will review the current status and challenges of metabolic engineering and will discuss how new technologies can enable metabolic engineering to be scaled up to the industrial level, either by cutting off the lines of control for endogenous metabolism or by infiltrating the system with disruptive, heterologous pathways that overcome cellular regulation. PMID:26967285

  10. Cellular Morphogenesis In Silico

    PubMed Central

    Shinbrot, Troy; Chun, Young; Caicedo-Carvajal, Carlos; Foty, Ramsey

    2009-01-01

    Abstract We describe a model that simulates spherical cells of different types that can migrate and interact either attractively or repulsively. We find that both expected morphologies and previously unreported patterns spontaneously self-assemble. Among the newly discovered patterns are a segmented state of alternating discs, and a “shish-kebab” state, in which one cell type forms a ring around a second type. We show that these unique states result from cellular attraction that increases with distance (e.g., as membranes stretch viscoelastically), and would not be seen in traditional, e.g., molecular, potentials that diminish with distance. Most of the states found computationally have been observed in vitro, and it remains to be established what role these self-assembled states may play in in vivo morphogenesis. PMID:19686642

  11. Cells anticipate periodic events

    NASA Astrophysics Data System (ADS)

    Nakagaki, Toshiyuki

    2009-03-01

    We show that an amoeboid organism can anticipate the timing of periodic events. The plasmodium of the true slime mold Physarum polycephalum moves rapidly under favourable conditions, but stops moving when transferred to less-favourable conditions. Plasmodia exposed to unfavourable conditions, presented in three consecutive pulses at constant intervals, reduced their locomotive speed in response to each episode. When subsequently subjected to favourable conditions, the plasmodia spontaneously reduced their locomotive speed at the time point when the next unfavourable episode would have occurred. This implied anticipation of impending environmental change. After this behaviour had been evoked several times, the locomotion of the plasmodia returned to normal; however, the anticipatory response could subsequently be induced by a single unfavourable pulse, implying recall of the memorized periodicity. We explored the mechanisms underlying these behaviours from a dynamical systems perspective. Our results hint at the cellular origins of primitive intelligence and imply that simple dynamics might be sufficient to explain its emergence.

  12. Common approaches for adolescents.

    PubMed

    1998-01-01

    A South-South program organized by JOICFP provided an excellent opportunity for the exchange of experiences in the field of adolescent reproductive health (RH) between Mexico and the Philippines. Alfonso Lopez Juarez, executive director, Mexican Foundation for Family Planning (MEXFAM), shared MEXFAM's experiences with field personnel and GO-NGO representatives related to JOICFP's RH-oriented project in the Philippines while in the country from November 16 to 21. The program was also effective for identifying common issues and effective approaches to adolescent health issues and communicating with youth on RH and sexual health. The exchange was supported by the Hoken Kaikan Foundation and organized by JOICFP in collaboration with UNFPA-Manila and the Commission on Population (POPCOM). Lopez shared some of the lessons of MEXFAM's decade-long Gente Joven IEC program on adolescent health with GO and NGO representatives at a forum held on November 18. The event was opened by Dr. Carmencita Reodica, secretary, Department of Health (DOH). He then moved to the project sites of Balayan and Malvar municipalities of Batangas Province, where he spoke with field staff and demonstrated MEXFAM's approach in classroom situations with young people. Lopez also observed various adolescent activities such as group work with peer facilitators. "I am pleased that we can share some applicable experiences and learn from each other's projects," commented Lopez. PMID:12348336

  13. Inducing cellular senescence using defined genetic elements.

    PubMed

    Nakagawa, Hiroshi; Opitz, Oliver G

    2007-01-01

    Cellular senescence is generally defined as an irreversible state of G1 cell cycle arrest in which cells are refractory to growth factor stimulation. Cellular senescence can be induced through several different mechanisms. Primary mammalian cells display a finite life span, suggesting a mechanism that counts cell divisions. Those cells initially proliferate but eventually enter a state of permanent growth arrest, called replicative senescence. Erosion of telomeric DNA has emerged as a key factor in replicative senescence, which is antagonized during cell immortalization. Nevertheless, besides telomere shortening, there are other mechanisms inducing a growth arrest similar to the replicative senescencent phenotype. Oncogenic or mitogenic signals as well as DNA damage can induce such a phenotype of cellular senescence. All forms of cellular senescence share common signaling pathways and morphological features. Thereby, p53 seems to be essential for the senescence response. Many of these senescence inducing mechanisms can be experimentally recapitulated by the introduction of defined genetic elements. Replicative senescence due to telomere shortening can, for example, be induced by a dominant negative version of telomerase, premature senescence by the overexpression of oncogenic ras, or p16. PMID:17634581

  14. Migraine and Common Morbidities

    MedlinePlus

    ... headaches . Home > Migraine and Common Morbidities Print Email Migraine and Common Morbidities ACHE Newsletter Sign up for ... newsletter by entering your e-mail address below. Migraine and Common Morbidities For many patients, migraine is ...

  15. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Robert; Novack, Steven

    2015-01-01

    Space Launch System (SLS) Agenda: Objective; Key Definitions; Calculating Common Cause; Examples; Defense against Common Cause; Impact of varied Common Cause Failure (CCF) and abortability; Response Surface for various CCF Beta; Takeaways.

  16. Event extraction with complex event classification using rich features.

    PubMed

    Miwa, Makoto; Saetre, Rune; Kim, Jin-Dong; Tsujii, Jun'ichi

    2010-02-01

    Biomedical Natural Language Processing (BioNLP) attempts to capture biomedical phenomena from texts by extracting relations between biomedical entities (i.e. proteins and genes). Traditionally, only binary relations have been extracted from large numbers of published papers. Recently, more complex relations (biomolecular events) have also been extracted. Such events may include several entities or other relations. To evaluate the performance of the text mining systems, several shared task challenges have been arranged for the BioNLP community. With a common and consistent task setting, the BioNLP'09 shared task evaluated complex biomolecular events such as binding and regulation.Finding these events automatically is important in order to improve biomedical event extraction systems. In the present paper, we propose an automatic event extraction system, which contains a model for complex events, by solving a classification problem with rich features. The main contributions of the present paper are: (1) the proposal of an effective bio-event detection method using machine learning, (2) provision of a high-performance event extraction system, and (3) the execution of a quantitative error analysis. The proposed complex (binding and regulation) event detector outperforms the best system from the BioNLP'09 shared task challenge. PMID:20183879

  17. Cellular and molecular introduction to brain development.

    PubMed

    Jiang, Xiangning; Nardelli, Jeannette

    2016-08-01

    Advances in the study of brain development over the last decades, especially recent findings regarding the evolutionary expansion of the human neocortex, and large-scale analyses of the proteome/transcriptome in the human brain, have offered novel insights into the molecular mechanisms guiding neural maturation, and the pathophysiology of multiple forms of neurological disorders. As a preamble to reviews of this issue, we provide an overview of the cellular, molecular and genetic bases of brain development with an emphasis on the major mechanisms associated with landmarks of normal neural development in the embryonic stage and early postnatal life, including neural stem/progenitor cell proliferation, cortical neuronal migration, evolution and folding of the cerebral cortex, synaptogenesis and neural circuit development, gliogenesis and myelination. We will only briefly depict developmental disorders that result from perturbations of these cellular or molecular mechanisms, and the most common perinatal brain injuries that could disturb normal brain development. PMID:26184894

  18. Cellular energy metabolism

    SciTech Connect

    Glaser, M.

    1991-06-01

    Studies have been carried out on adenylate kinase which is an important enzyme in determining the concentrations of the adenine nucleotides. An efficient method has been developed to clone mutant adenylate kinase genes in E. coli. Site-specific mutagenesis of the wild type gene also has been used to obtain forms of adenylate kinase with altered amino acids. The wild type and mutant forms of adenylate kinase have been overexpressed and large quantities were readily isolated. The kinetic and fluorescence properties of the different forms of adenylate kinase were characterized. This has led to a new model for the location of the AMP and ATP bindings sites on the enzyme and a proposal for the mechanism of substrate inhibition. Crystals of the wild type enzyme were obtained that diffract to at least 2.3 {angstrom} resolution. Experiments were also initiated to determine the function of adenylate kinase in vivo. In one set of experiments, E. coli strains with mutations in adenylate kinase showed large changes in cellular nucleotides after reaching the stationary phase in a low phosphate medium. This was caused by selective proteolytic degradation of the mutant adenylate kinase caused by phosphate starvation.

  19. Molecular and Cellular Biophysics

    NASA Astrophysics Data System (ADS)

    Jackson, Meyer B.

    2006-01-01

    Molecular and Cellular Biophysics provides advanced undergraduate and graduate students with a foundation in the basic concepts of biophysics. Students who have taken physical chemistry and calculus courses will find this book an accessible and valuable aid in learning how these concepts can be used in biological research. The text provides a rigorous treatment of the fundamental theories in biophysics and illustrates their application with examples. Conformational transitions of proteins are studied first using thermodynamics, and subsequently with kinetics. Allosteric theory is developed as the synthesis of conformational transitions and association reactions. Basic ideas of thermodynamics and kinetics are applied to topics such as protein folding, enzyme catalysis and ion channel permeation. These concepts are then used as the building blocks in a treatment of membrane excitability. Through these examples, students will gain an understanding of the general importance and broad applicability of biophysical principles to biological problems. Offers a unique synthesis of concepts across a wide range of biophysical topics Provides a rigorous theoretical treatment, alongside applications in biological systems Author has been teaching biophysics for nearly 25 years

  20. Electrosurgery with cellular precision.

    PubMed

    Palanker, Daniel V; Vankov, Alexander; Huie, Philip

    2008-02-01

    Electrosurgery, one of the most-often used surgical tools, is a robust but somewhat crude technology that has changed surprisingly little since its invention almost a century ago. Continuous radiofrequency is still used for tissue cutting, with thermal damage extending to hundreds of micrometers. In contrast, lasers developed 70 years later, have been constantly perfected, and the laser-tissue interactions explored in great detail, which has allowed tissue ablation with cellular precision in many laser applications. We discuss mechanisms of tissue damage by electric field, and demonstrate that electrosurgery with properly optimized waveforms and microelectrodes can rival many advanced lasers. Pulsed electric waveforms with burst durations ranging from 10 to 100 micros applied via insulated planar electrodes with 12 microm wide exposed edges produced plasma-mediated dissection of tissues with the collateral damage zone ranging from 2 to 10 microm. Length of the electrodes can vary from micrometers to centimeters and all types of soft tissues-from membranes to cartilage and skin could be dissected in liquid medium and in a dry field. This technology may allow for major improvements in outcomes of the current surgical procedures and development of much more refined surgical techniques. PMID:18270030

  1. Active Cellular Nematics

    NASA Astrophysics Data System (ADS)

    Duclos, Guillaume; Erlenkaemper, Christoph; Garcia, Simon; Yevick, Hannah; Joanny, Jean-François; Silberzan, Pascal; Biology inspired physics at mesoscales Team; Physical approach of biological problems Team

    We study the emergence of a nematic order in a two-dimensional tissue of apolar elongated fibroblast cells. Initially, these cells are very motile and the monolayer is characterized by giant density fluctuations, a signature of far-from-equilibrium systems. As the cell density increases because of proliferation, the cells align with each other forming large perfectly oriented domains while the cellular movements slow down and eventually freeze. Therefore topological defects characteristic of nematic phases remain trapped at long times, preventing the development of infinite domains. By analogy with classical non-active nematics, we have investigated the role of boundaries and we have shown that cells confined in stripes of width smaller than typically 500 µm are perfectly aligned in the stripe direction. Experiments performed in cross-shaped patterns show that both the number of cells and the degree of alignment impact the final orientation. Reference: Duclos G., Garcia S., Yevick H.G. and Silberzan P., ''Perfect nematic order in confined monolayers of spindle-shaped cells'', Soft Matter, 10, 14, 2014

  2. Common Career Technical Core: Common Standards, Common Vision for CTE

    ERIC Educational Resources Information Center

    Green, Kimberly

    2012-01-01

    This article provides an overview of the National Association of State Directors of Career Technical Education Consortium's (NASDCTEc) Common Career Technical Core (CCTC), a state-led initiative that was created to ensure that career and technical education (CTE) programs are consistent and high quality across the United States. Forty-two states,…

  3. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  4. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular markets. 22.909 Section 22.909... Cellular Radiotelephone Service § 22.909 Cellular markets. Cellular markets are standard geographic areas used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  5. Different Kinds of Causality in Event Cognition

    ERIC Educational Resources Information Center

    Radvansky, Gabriel A.; Tamplin, Andrea K.; Armendarez, Joseph; Thompson, Alexis N.

    2014-01-01

    Narrative memory is better for information that is more causally connected and occurs at event boundaries, such as a causal break. However, it is unclear whether there are common or distinct influences of causality. For the event boundaries that arise as a result of causal breaks, the events that follow may subsequently become more causally…

  6. Events diary

    NASA Astrophysics Data System (ADS)

    2000-01-01

    as Imperial College, the Royal Albert Hall, the Royal College of Art, the Natural History and Science Museums and the Royal Geographical Society. Under the heading `Shaping the future together' BA2000 will explore science, engineering and technology in their wider cultural context. Further information about this event on 6 - 12 September may be obtained from Sandra Koura, BA2000 Festival Manager, British Association for the Advancement of Science, 23 Savile Row, London W1X 2NB (tel: 0171 973 3075, e-mail: sandra.koura@britassoc.org.uk ). Details of the creating SPARKS events may be obtained from creating.sparks@britassoc.org.uk or from the website www.britassoc.org.uk . Other events 3 - 7 July, Porto Alegre, Brazil VII Interamerican conference on physics education: The preparation of physicists and physics teachers in contemporary society. Info: IACPE7@if.ufrgs.br or cabbat1.cnea.gov.ar/iacpe/iacpei.htm 27 August - 1 September, Barcelona, Spain GIREP conference: Physics teacher education beyond 2000. Info: www.blues.uab.es/phyteb/index.html

  7. MSAT and cellular hybrid networking

    NASA Technical Reports Server (NTRS)

    Baranowsky, Patrick W., II

    1993-01-01

    Westinghouse Electric Corporation is developing both the Communications Ground Segment and the Series 1000 Mobile Phone for American Mobile Satellite Corporation's (AMSC's) Mobile Satellite (MSAT) system. The success of the voice services portion of this system depends, to some extent, upon the interoperability of the cellular network and the satellite communication circuit switched communication channels. This paper will describe the set of user-selectable cellular interoperable modes (cellular first/satellite second, etc.) provided by the Mobile Phone and described how they are implemented with the ground segment. Topics including roaming registration and cellular-to-satellite 'seamless' call handoff will be discussed, along with the relevant Interim Standard IS-41 Revision B Cellular Radiotelecommunications Intersystem Operations and IOS-553 Mobile Station - Land Station Compatibility Specification.

  8. Common Interventional Radiology Procedures

    MedlinePlus

    ... of common interventional techniques is below. Common Interventional Radiology Procedures Angiography An X-ray exam of the ... into the vertebra. Copyright © 2016 Society of Interventional Radiology. All rights reserved. 3975 Fair Ridge Drive • Suite ...

  9. How Common Is the Common Core?

    ERIC Educational Resources Information Center

    Thomas, Amande; Edson, Alden J.

    2014-01-01

    Since the introduction of the Common Core State Standards for Mathematics (CCSSM) in 2010, stakeholders in adopting states have engaged in a variety of activities to understand CCSSM standards and transition from previous state standards. These efforts include research, professional development, assessment and modification of curriculum resources,…

  10. Pirin Inhibits Cellular Senescence in Melanocytic Cells

    PubMed Central

    Licciulli, Silvia; Luise, Chiara; Scafetta, Gaia; Capra, Maria; Giardina, Giuseppina; Nuciforo, Paolo; Bosari, Silvano; Viale, Giuseppe; Mazzarol, Giovanni; Tonelli, Chiara; Lanfrancone, Luisa; Alcalay, Myriam

    2011-01-01

    Cellular senescence has been widely recognized as a tumor suppressing mechanism that acts as a barrier to cancer development after oncogenic stimuli. A prominent in vivo model of the senescence barrier is represented by nevi, which are composed of melanocytes that, after an initial phase of proliferation induced by activated oncogenes (most commonly BRAF), are blocked in a state of cellular senescence. Transformation to melanoma occurs when genes involved in controlling senescence are mutated or silenced and cells reacquire the capacity to proliferate. Pirin (PIR) is a highly conserved nuclear protein that likely functions as a transcriptional regulator whose expression levels are altered in different types of tumors. We analyzed the expression pattern of PIR in adult human tissues and found that it is expressed in melanocytes and has a complex pattern of regulation in nevi and melanoma: it is rarely detected in mature nevi, but is expressed at high levels in a subset of melanomas. Loss of function and overexpression experiments in normal and transformed melanocytic cells revealed that PIR is involved in the negative control of cellular senescence and that its expression is necessary to overcome the senescence barrier. Our results suggest that PIR may have a relevant role in melanoma progression. PMID:21514450

  11. The New Common School.

    ERIC Educational Resources Information Center

    Glenn, Charles L.

    1987-01-01

    Horace Mann's goal of creating a common school that brings our society's children together in mutual respect and common learning need not be frustrated by residential segregation and geographical separation of the haves and have-nots. Massachusetts' new common school vision boasts a Metro Program for minority students, 80 magnet schools, and…

  12. Knowledge representation for commonality

    NASA Technical Reports Server (NTRS)

    Yeager, Dorian P.

    1990-01-01

    Domain-specific knowledge necessary for commonality analysis falls into two general classes: commonality constraints and costing information. Notations for encoding such knowledge should be powerful and flexible and should appeal to the domain expert. The notations employed by the Commonality Analysis Problem Solver (CAPS) analysis tool are described. Examples are given to illustrate the main concepts.

  13. QUANTITATIVE IN VITRO MEASUREMENT OF CELLULAR PROCESSES CRITICAL TO THE DEVELOPMENT OF NEURAL CONNECTIVITY USING HCA.

    EPA Science Inventory

    New methods are needed to screen thousands of environmental chemicals for toxicity, including developmental neurotoxicity. In vitro, cell-based assays that model key cellular events have been proposed for high throughput screening of chemicals for developmental neurotoxicity. Whi...

  14. Hippocampal ensemble dynamics timestamp events in long-term memory

    PubMed Central

    Rubin, Alon; Geva, Nitzan; Sheintuch, Liron; Ziv, Yaniv

    2015-01-01

    The capacity to remember temporal relationships between different events is essential to episodic memory, but little is currently known about its underlying mechanisms. We performed time-lapse imaging of thousands of neurons over weeks in the hippocampal CA1 of mice as they repeatedly visited two distinct environments. Longitudinal analysis exposed ongoing environment-independent evolution of episodic representations, despite stable place field locations and constant remapping between the two environments. These dynamics time-stamped experienced events via neuronal ensembles that had cellular composition and activity patterns unique to specific points in time. Temporally close episodes shared a common timestamp regardless of the spatial context in which they occurred. Temporally remote episodes had distinct timestamps, even if they occurred within the same spatial context. Our results suggest that days-scale hippocampal ensemble dynamics could support the formation of a mental timeline in which experienced events could be mnemonically associated or dissociated based on their temporal distance. DOI: http://dx.doi.org/10.7554/eLife.12247.001 PMID:26682652

  15. Cellular compartmentalization of secondary metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors sh...

  16. Cellular therapy for haematological malignancies.

    PubMed

    Roddie, P H; Turner, M L

    2002-11-01

    The aim of this review was to summarize the recent progress made in the field of cellular therapeutics in haematological malignancy. The review also examined the role that the National Transfusion Services might play in the manufacture of new cellular therapeutic agents, given both their expertise in the safe provision of blood products and their possession of accredited cell manipulation facilities. Cellular therapy is entering an era in which novel cellular products will find increasing clinical use, particularly in the areas of haematopoietic stem cell transplantation and immunotherapy. The production of novel cell-based therapies, both in Europe and North America, is now under strict regulatory control and therefore collaboration with the National Transfusion Services in the manufacture of these agents may well be beneficial if the production standards demanded by the regulatory authorities are to be fulfilled. PMID:12437515

  17. Mathematical Modeling of Cellular Metabolism.

    PubMed

    Berndt, Nikolaus; Holzhütter, Hermann-Georg

    2016-01-01

    Cellular metabolism basically consists of the conversion of chemical compounds taken up from the extracellular environment into energy (conserved in energy-rich bonds of organic phosphates) and a wide array of organic molecules serving as catalysts (enzymes), information carriers (nucleic acids), and building blocks for cellular structures such as membranes or ribosomes. Metabolic modeling aims at the construction of mathematical representations of the cellular metabolism that can be used to calculate the concentration of cellular molecules and the rates of their mutual chemical interconversion in response to varying external conditions as, for example, hormonal stimuli or supply of essential nutrients. Based on such calculations, it is possible to quantify complex cellular functions as cellular growth, detoxification of drugs and xenobiotic compounds or synthesis of exported molecules. Depending on the specific questions to metabolism addressed, the methodological expertise of the researcher, and available experimental information, different conceptual frameworks have been established, allowing the usage of computational methods to condense experimental information from various layers of organization into (self-) consistent models. Here, we briefly outline the main conceptual frameworks that are currently exploited in metabolism research. PMID:27557541

  18. Common ecology quantifies human insurgency.

    PubMed

    Bohorquez, Juan Camilo; Gourley, Sean; Dixon, Alexander R; Spagat, Michael; Johnson, Neil F

    2009-12-17

    Many collective human activities, including violence, have been shown to exhibit universal patterns. The size distributions of casualties both in whole wars from 1816 to 1980 and terrorist attacks have separately been shown to follow approximate power-law distributions. However, the possibility of universal patterns ranging across wars in the size distribution or timing of within-conflict events has barely been explored. Here we show that the sizes and timing of violent events within different insurgent conflicts exhibit remarkable similarities. We propose a unified model of human insurgency that reproduces these commonalities, and explains conflict-specific variations quantitatively in terms of underlying rules of engagement. Our model treats each insurgent population as an ecology of dynamically evolving, self-organized groups following common decision-making processes. Our model is consistent with several recent hypotheses about modern insurgency, is robust to many generalizations, and establishes a quantitative connection between human insurgency, global terrorism and ecology. Its similarity to financial market models provides a surprising link between violent and non-violent forms of human behaviour. PMID:20016600

  19. Creating Special Events

    ERIC Educational Resources Information Center

    deLisle, Lee

    2009-01-01

    "Creating Special Events" is organized as a systematic approach to festivals and events for students who seek a career in event management. This book looks at the evolution and history of festivals and events and proceeds to the nuts and bolts of event management. The book presents event management as the means of planning, organizing, directing,…

  20. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  1. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  2. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  3. 47 CFR 32.5003 - Cellular mobile revenue.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular mobile revenue. 32.5003 Section 32.5003 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES UNIFORM SYSTEM OF ACCOUNTS FOR TELECOMMUNICATIONS COMPANIES Instructions For Revenue Accounts § 32.5003...

  4. Connecting Photosynthesis and Cellular Respiration: Preservice Teachers' Conceptions

    ERIC Educational Resources Information Center

    Brown, Mary H.; Schwartz, Renee S.

    2009-01-01

    The biological processes of photosynthesis and plant cellular respiration include multiple biochemical steps, occur simultaneously within plant cells, and share common molecular components. Yet, learners often compartmentalize functions and specialization of cell organelles relevant to these two processes, without considering the interconnections…

  5. Hypoxia Defined as a Common Culprit/Initiation Factor in Mitochondrial-Mediated Proinflammatory Processes

    PubMed Central

    Stefano, George B.; Kream, Richard M.

    2015-01-01

    In mammals and invertebrates, the activities of neuro- and immuno-competent cells, e.g., glia, which are present in nervous tissues, are deemed of critical importance to normative neuronal function. The responsiveness of invertebrate and vertebrate immuno-competent glia to a common set of signal molecules, such as nitric oxide and endogenous morphine, is functionally linked to physiologically driven innate immunological and neuronal activities. Importantly, the presence of a common, evolutionarily conserved, set of signal molecules in comparative animal groups strongly suggests an expansive intermediate metabolic profile dependent on high output mitochondrial ATP production and utilization. Normative bidirectional neural-immune communication across invertebrate and vertebrate species requires common anatomical and biochemical substrates and pathways involved in energy production and mitochondrial integrity. Within this closed-loop system, abnormal perturbation of the respective tissue functions will have profound ramifications in functionally altering associated nervous and vascular systems and it is highly likely that the initial trigger to the induction of a physiologically debilitating pro-inflammatory state is a micro-environmental hypoxic event. This is surmised by the need for an unwavering constant oxygen supply. In this case, temporal perturbations of normative oxygen tension may be tolerated for short, but not extended, periods and ischemic/hypoxic perturbations in oxygen delivery represent significant physiological challenges to overall cellular and multiple organ system viability. Hence, hypoxic triggering of multiple pro-inflammatory events, if not corrected, will promote pathophysiological amplification leading to a deleterious cascade of bio-senescent cellular and molecular signaling pathways, which converge to markedly impair mitochondrial energy utilization and ATP production. PMID:25997954

  6. Event group importance measures for top event frequency analyses

    SciTech Connect

    1995-07-31

    Three traditional importance measures, risk reduction, partial derivative, nd variance reduction, have been extended to permit analyses of the relative importance of groups of underlying failure rates to the frequencies of resulting top events. The partial derivative importance measure was extended by assessing the contribution of a group of events to the gradient of the top event frequency. Given the moments of the distributions that characterize the uncertainties in the underlying failure rates, the expectation values of the top event frequency, its variance, and all of the new group importance measures can be quantified exactly for two familiar cases: (1) when all underlying failure rates are presumed independent, and (2) when pairs of failure rates based on common data are treated as being equal (totally correlated). In these cases, the new importance measures, which can also be applied to assess the importance of individual events, obviate the need for Monte Carlo sampling. The event group importance measures are illustrated using a small example problem and demonstrated by applications made as part of a major reactor facility risk assessment. These illustrations and applications indicate both the utility and the versatility of the event group importance measures.

  7. Open cellular structure in marine stratocumulus sheets

    SciTech Connect

    Wood, Robert; Comstock, K. K.; Bretherton, Christopher S.; Cornish, C.; Tomlinson, Jason M.; Collins, Donald R.; Fairall, C.

    2008-06-25

    Geostationary and sunsynchronous satellite data and in-situ observations from ship cruises are used to investigate the formation of open cellular structure in marine stratocumulus clouds over the Southeast Pacific (SEP). Open cellular convection either forms spontaneously as pockets of open cells (POCs) within overcast stratocumulus, or is advected into the region from midlatitude regions. POC formation occurs most frequently during the latter part of the night demonstrating that this transition is not caused by solar absorption-driven decoupling. The transition preferentially occurs in clouds with low 11-3.7 microns nighttime brightness temperature difference (BTD) which is found to be well correlated with both in-situ measured accumulation mode aerosol concentration and cloud droplet concentration estimates derived from MODIS. Besides indicating that night time BTD is an excellent proxy for stratocumulus cloud droplet concentration Nd, this also suggests that low aerosol concentrations favor POC formation. Indeed, extremely low accumulation mode aerosol concentrations are found during the passage of open cell events over the ship. Free-tropospheric moisture is not found to be an important factor in POC formation. Significant subseasonal variability occurs in the fractional coverage of open cellular convection over the broader SEP. This coverage is well correlated with a MODIS-derived drizzle proxy (MDP) proportional to the ratio of liquid water path (LWP) to Nd for predominantly overcast regions. Both LWP and Nd variability influences the MDP. Periods of low MDP have significant positive large scale Nd anomalies and are preceded byoffshore winds at 850 hPa, which suggests a potential continental influence upon open cell formation over the SEP. Together, the results suggest important two-way interactions between aerosols and drizzle in marine stratocumulus and a role for drizzle in modulating the large scale albedo of these cloud systems.

  8. Cellular telephone-based radiation detection instrument

    DOEpatents

    Craig, William W.; Labov, Simon E.

    2011-06-14

    A network of radiation detection instruments, each having a small solid state radiation sensor module integrated into a cellular phone for providing radiation detection data and analysis directly to a user. The sensor module includes a solid-state crystal bonded to an ASIC readout providing a low cost, low power, light weight compact instrument to detect and measure radiation energies in the local ambient radiation field. In particular, the photon energy, time of event, and location of the detection instrument at the time of detection is recorded for real time transmission to a central data collection/analysis system. The collected data from the entire network of radiation detection instruments are combined by intelligent correlation/analysis algorithms which map the background radiation and detect, identify and track radiation anomalies in the region.

  9. Sound attenuation characteristics of cellular metamaterials

    NASA Astrophysics Data System (ADS)

    Varanasi, Satya Surya Srinivas

    The objectives of this work were to develop lightweight barrier and compact absorbing material systems for controlling low frequency noise (say below 2 kHz). The solutions explored fell into the broad category of segmented cellular materials in which local resonances are built-in attributes. The body of the work was divided into four parts. First, a cellular metamaterial concept for lightweight barrier materials was proposed, then, secondly, the concept was experimentally verified by testing application-scale designs in a diffuse sound field setup. In the remaining two parts of the work, the idea of shifting sound energy emporally and spatially was explored as a means of improving the performance of metamaterial-based barrier solutions and of compact sound absorbers, respectively. The high sound transmission loss (STL) metamaterials described to-date commonly require the introduction of relatively heavy resonating or constraining components which runs counter to the desire to create lightweight barrier solutions. It was proposed here that a cellular panel comprising a periodic arrangement of unit cells consisting of plates held in a grid-like frame, which itself is unsupported, can possess a high STL within a specified frequency range without an undue mass penalty. It was numerically demonstrated that such a cellular panel can yield enhanced STL if the unit cell mass is apportioned appropriately between the unit cell plate and the surrounding grid-like frame. The concept of planar cellular metamaterials was verified through diffuse field experiments on application-scale specimens by using intensity methods. Two cellular panel designs were tested and their behavior was compared with that of a reference limp panel. It was found that the predicted benefit of the cellular panels could be realized by increasing the mass contrast in the designs, and that the benefit was reduced with increasing diffuseness of the sound field. It was also found that the loss in performance

  10. Early cellular signaling responses to axonal injury

    PubMed Central

    Lukas, Thomas J; Wang, Ai Ling; Yuan, Ming; Neufeld, Arthur H

    2009-01-01

    Background We have used optic nerve injury as a model to study early signaling events in neuronal tissue following axonal injury. Optic nerve injury results in the selective death of retinal ganglion cells (RGCs). The time course of cell death takes place over a period of days with the earliest detection of RGC death at about 48 hr post injury. We hypothesized that in the period immediately following axonal injury, there are changes in the soma that signal surrounding glia and neurons and that start programmed cell death. In the current study, we investigated early changes in cellular signaling and gene expression that occur within the first 6 hrs post optic nerve injury. Results We found evidence of cell to cell signaling within 30 min of axonal injury. We detected differences in phosphoproteins and gene expression within the 6 hrs time period. Activation of TNFα and glutamate receptors, two pathways that can initiate cell death, begins in RGCs within 6 hrs following axonal injury. Differential gene expression at 6 hrs post injury included genes involved in cytokine, neurotrophic factor signaling (Socs3) and apoptosis (Bax). Conclusion We interpret our studies to indicate that both neurons and glia in the retina have been signaled within 30 min after optic nerve injury. The signals are probably initiated by the RGC soma. In addition, signals activating cellular death pathways occur within 6 hrs of injury, which likely lead to RGC degeneration. PMID:19284657

  11. Cellular commitment in the developing cerebellum

    PubMed Central

    Marzban, Hassan; Del Bigio, Marc R.; Alizadeh, Javad; Ghavami, Saeid; Zachariah, Robby M.; Rastegar, Mojgan

    2014-01-01

    The mammalian cerebellum is located in the posterior cranial fossa and is critical for motor coordination and non-motor functions including cognitive and emotional processes. The anatomical structure of cerebellum is distinct with a three-layered cortex. During development, neurogenesis and fate decisions of cerebellar primordium cells are orchestrated through tightly controlled molecular events involving multiple genetic pathways. In this review, we will highlight the anatomical structure of human and mouse cerebellum, the cellular composition of developing cerebellum, and the underlying gene expression programs involved in cell fate commitments in the cerebellum. A critical evaluation of the cell death literature suggests that apoptosis occurs in ~5% of cerebellar cells, most shortly after mitosis. Apoptosis and cellular autophagy likely play significant roles in cerebellar development, we provide a comprehensive discussion of their role in cerebellar development and organization. We also address the possible function of unfolded protein response in regulation of cerebellar neurogenesis. We discuss recent advancements in understanding the epigenetic signature of cerebellar compartments and possible connections between DNA methylation, microRNAs and cerebellar neurodegeneration. Finally, we discuss genetic diseases associated with cerebellar dysfunction and their role in the aging cerebellum. PMID:25628535

  12. Fracture mechanics of cellular glass

    NASA Technical Reports Server (NTRS)

    Zwissler, J. G.; Adams, M. A.

    1981-01-01

    The fracture mechanics of cellular glasses (for the structural substrate of mirrored glass for solr concentrator reflecting panels) are discussed. Commercial and developmental cellular glasses were tested and analyzed using standard testing techniques and models developed from linear fracture mechanics. Two models describing the fracture behavior of these materials were developed. Slow crack growth behavior in cellular glass was found to be more complex than that encountered in dense glasses or ceramics. The crack velocity was found to be strongly dependent upon water vapor transport to the tip of the moving crack. The existence of a static fatigue limit was not conclusively established, however, it is speculated that slow crack growth behavior in Region 1 may be slower, by orders of magnitude, than that found in dense glasses.

  13. Cellular-based preemption system

    NASA Technical Reports Server (NTRS)

    Bachelder, Aaron D. (Inventor)

    2011-01-01

    A cellular-based preemption system that uses existing cellular infrastructure to transmit preemption related data to allow safe passage of emergency vehicles through one or more intersections. A cellular unit in an emergency vehicle is used to generate position reports that are transmitted to the one or more intersections during an emergency response. Based on this position data, the one or more intersections calculate an estimated time of arrival (ETA) of the emergency vehicle, and transmit preemption commands to traffic signals at the intersections based on the calculated ETA. Additional techniques may be used for refining the position reports, ETA calculations, and the like. Such techniques include, without limitation, statistical preemption, map-matching, dead-reckoning, augmented navigation, and/or preemption optimization techniques, all of which are described in further detail in the above-referenced patent applications.

  14. Types or States? Cellular Dynamics and Regenerative Potential.

    PubMed

    Adler, Carolyn E; Sánchez Alvarado, Alejandro

    2015-11-01

    Many of our organs can maintain and repair themselves during homeostasis and injury, as a result of the action of tissue-specific, multipotent stem cells. However, recent evidence from mammalian systems suggests that injury stimulates dramatic plasticity, or transient changes in cell potential, in both stem cells and more differentiated cells. Planarian flatworms possess abundant stem cells, making them an exceptional model for understanding the cellular behavior underlying homeostasis and regeneration. Recent discoveries of cell lineages and regeneration-specific events provide an initial framework for unraveling the complex cellular contributions to regeneration. In this review, we discuss the concept of cellular plasticity in the context of planarian regeneration, and consider the possibility that pluripotency may be a transient, probabilistic state exhibited by stem cells. PMID:26437587

  15. Synthetic biology in cellular immunotherapy

    PubMed Central

    Chakravarti, Deboki; Wong, Wilson W.

    2015-01-01

    The adoptive transfer of genetically engineered T cells with cancer-targeting receptors has shown tremendous promise for eradicating tumors in clinical trials. This form of cellular immunotherapy presents a unique opportunity to incorporate advanced systems and synthetic biology approaches to create cancer therapeutics with novel functions. Here, we first review the development of synthetic receptors, switches, and circuits to control the location, duration, and strength of T cell activity against tumors. In addition, we discuss the cellular engineering and genome editing of host cells (or the chassis) to improve the efficacy of cell-based cancer therapeutics, and to reduce the time and cost of manufacturing. PMID:26088008

  16. Global properties of cellular automata

    SciTech Connect

    Jen, E.

    1986-04-01

    Cellular automata are discrete mathematical systems that generate diverse, often complicated, behavior using simple deterministic rules. Analysis of the local structure of these rules makes possible a description of the global properties of the associated automata. A class of cellular automata that generate infinitely many aperoidic temporal sequences is defined,a s is the set of rules for which inverses exist. Necessary and sufficient conditions are derived characterizing the classes of ''nearest-neighbor'' rules for which arbitrary finite initial conditions (i) evolve to a homogeneous state; (ii) generate at least one constant temporal sequence.

  17. Cellular automaton for chimera states

    NASA Astrophysics Data System (ADS)

    García-Morales, Vladimir

    2016-04-01

    A minimalistic model for chimera states is presented. The model is a cellular automaton (CA) which depends on only one adjustable parameter, the range of the nonlocal coupling, and is built from elementary cellular automata and the majority (voting) rule. This suggests the universality of chimera-like behavior from a new point of view: Already simple CA rules based on the majority rule exhibit this behavior. After a short transient, we find chimera states for arbitrary initial conditions, the system spontaneously splitting into stable domains separated by static boundaries, some synchronously oscillating and the others incoherent. When the coupling range is local, nontrivial coherent structures with different periodicities are formed.

  18. Adaptive stochastic cellular automata: Applications

    NASA Astrophysics Data System (ADS)

    Qian, S.; Lee, Y. C.; Jones, R. D.; Barnes, C. W.; Flake, G. W.; O'Rourke, M. K.; Lee, K.; Chen, H. H.; Sun, G. Z.; Zhang, Y. Q.; Chen, D.; Giles, C. L.

    1990-09-01

    The stochastic learning cellular automata model has been applied to the problem of controlling unstable systems. Two example unstable systems studied are controlled by an adaptive stochastic cellular automata algorithm with an adaptive critic. The reinforcement learning algorithm and the architecture of the stochastic CA controller are presented. Learning to balance a single pole is discussed in detail. Balancing an inverted double pendulum highlights the power of the stochastic CA approach. The stochastic CA model is compared to conventional adaptive control and artificial neural network approaches.

  19. Cellular senescence in aging primates.

    PubMed

    Herbig, Utz; Ferreira, Mark; Condel, Laura; Carey, Dee; Sedivy, John M

    2006-03-01

    The aging of organisms is characterized by a gradual functional decline of all organ systems. Mammalian somatic cells in culture display a limited proliferative life span, at the end of which they undergo an irreversible cell cycle arrest known as replicative senescence. Whether cellular senescence contributes to organismal aging has been controversial. We investigated telomere dysfunction, a recently discovered biomarker of cellular senescence, and found that the number of senescent fibroblasts increases exponentially in the skin of aging baboons, reaching >15% of all cells in very old individuals. In addition, the same cells contain activated ataxia-telangiectasia mutated kinase and heterochromatinized nuclei, confirming their senescent status. PMID:16456035

  20. TDP-43 affects splicing profiles and isoform production of genes involved in the apoptotic and mitotic cellular pathways

    PubMed Central

    De Conti, Laura; Akinyi, Maureen V.; Mendoza-Maldonado, Ramiro; Romano, Maurizio; Baralle, Marco; Buratti, Emanuele

    2015-01-01

    In recent times, high-throughput screening analyses have broadly defined the RNA cellular targets of TDP-43, a nuclear factor involved in neurodegeneration. A common outcome of all these studies is that changing the expression levels of this protein can alter the expression of several hundred RNAs within cells. What still remains to be clarified is which changes represent direct cellular targets of TDP-43 or just secondary variations due to the general role played by this protein in RNA metabolism. Using an HTS-based splicing junction analysis we identified at least six bona fide splicing events that are consistent with being controlled by TDP-43. Validation of the data, both in neuronal and non-neuronal cell lines demonstrated that TDP-43 substantially alters the levels of isoform expression in four genes potentially important for neuropathology: MADD/IG20, STAG2, FNIP1 and BRD8. For MADD/IG20 and STAG2, these changes could also be confirmed at the protein level. These alterations were also observed in a cellular model that successfully mimics TDP-43 loss of function effects following its aggregation. Most importantly, our study demonstrates that cell cycle alterations induced by TDP-43 knockdown can be recovered by restoring the STAG2, an important component of the cohesin complex, normal splicing profile. PMID:26261209

  1. The channel-kinase TRPM7, revealing the untold story of Mg(2+) in cellular signaling.

    PubMed

    Schmitz, Carsten; Brandao, Katherine; Perraud, Anne-Laure

    2014-01-01

    Ion homeostasis dysregulations have severe effects on human health, impairing the effectiveness and appropriateness of major cellular events, including immune responses. The adverse effects of Mg(2+) deficiency on cellular physiology are well known and documented, but mechanistic insights into Mg(2+) sensitive signal transduction are still lacking. TRPM7 and its sister channel TRPM6 stand out as the only known fusions of an ion pore with a Ser/Thr kinase domain. Both channels are permeable to divalent cations and are central regulators of Mg(2+) homeostasis. One crucial aspect of TRPM7 function we have extensively studied is the relationship between its ion channel portion and its C-terminal Ser/Thr kinase domain. The modulation of ion channels by phosphorylation through exogenous kinases is common, however the covalent bound between the TRPM7 channel and its kinase suggests a novel kind of link between ion-entry and signal transduction events. Current knowledge supports a reciprocal "two-way street" model where TRPM7-kinase modulates ion transport function through Ser/Thr phosphorylation, and in turn, channel gating and ionic conditions in close proximity to the pore regulate TRPM7-kinase mediated signaling. We have shown that TRPM7 acts as a sensor of Mg(2+)-availability, adjusting key cellular functions such as the rate of cellular protein translation to the Mg(2+) nutritional status. Since molecular mechanisms controlling rates of protein translation are critical for cell growth and division in response to nutrient availability, this could have relevance for example for therapies targeted at molecules shaping the cancerous translational apparatus. In our quest to understand the biology of Mg(2+) in the context of immune responses, we found that TRPM7 associates with, and phosphorylates phospholipase C gamma 2 (PLCγ2), a pivotal molecule in the signaling pathway following B-cell receptor (BCR) activation. This contributes to the Mg(2+)-dependent modulation of

  2. Biological magnetic cellular spheroids as building blocks for tissue engineering

    PubMed Central

    Mattix, Brandon; Olsen, Timothy R.; Gu, Yu; Casco, Megan; Herbst, Austin; Simionescu, Dan T.; Visconti, Richard P.; Kornev, Konstantin G.; Alexis, Frank

    2016-01-01

    Magnetic nanoparticles (MNPs), primarily iron oxide nanoparticles, have been incorporated into cellular spheroids to allow for magnetic manipulation into desired shapes, patterns and 3-D tissue constructs using magnetic forces. However, the direct and long-term interaction of iron oxide nanoparticles with cells and biological systems can induce adverse effects on cell viability, phenotype and function, and remain a critical concern. Here we report the preparation of biological magnetic cellular spheroids containing magnetoferritin, a biological MNP, capable of serving as a biological alternative to iron oxide magnetic cellular spheroids as tissue engineered building blocks. Magnetoferritin NPs were incorporated into 3-D cellular spheroids with no adverse effects on cell viability up to 1 week. Additionally, cellular spheroids containing magnetoferritin NPs were magnetically patterned and fused into a tissue ring to demonstrate its potential for tissue engineering applications. These results present a biological approach that can serve as an alternative to the commonly used iron oxide magnetic cellular spheroids, which often require complex surface modifications of iron oxide NPs to reduce the adverse effects on cells. PMID:24176725

  3. Biological magnetic cellular spheroids as building blocks for tissue engineering.

    PubMed

    Mattix, Brandon; Olsen, Timothy R; Gu, Yu; Casco, Megan; Herbst, Austin; Simionescu, Dan T; Visconti, Richard P; Kornev, Konstantin G; Alexis, Frank

    2014-02-01

    Magnetic nanoparticles (MNPs), primarily iron oxide nanoparticles, have been incorporated into cellular spheroids to allow for magnetic manipulation into desired shapes, patterns and 3-D tissue constructs using magnetic forces. However, the direct and long-term interaction of iron oxide nanoparticles with cells and biological systems can induce adverse effects on cell viability, phenotype and function, and remain a critical concern. Here we report the preparation of biological magnetic cellular spheroids containing magnetoferritin, a biological MNP, capable of serving as a biological alternative to iron oxide magnetic cellular spheroids as tissue engineered building blocks. Magnetoferritin NPs were incorporated into 3-D cellular spheroids with no adverse effects on cell viability up to 1 week. Additionally, cellular spheroids containing magnetoferritin NPs were magnetically patterned and fused into a tissue ring to demonstrate its potential for tissue engineering applications. These results present a biological approach that can serve as an alternative to the commonly used iron oxide magnetic cellular spheroids, which often require complex surface modifications of iron oxide NPs to reduce the adverse effects on cells. PMID:24176725

  4. Performance evaluation of cellular phone network based portable ECG device.

    PubMed

    Hong, Joo-Hyun; Cha, Eun-Jong; Lee, Tae-Soo

    2008-01-01

    In this study, cellular phone network based portable ECG device was developed and three experiments were performed to evaluate the accuracy, reliability and operability, applicability during daily life of the developed device. First, ECG signals were measured using the developed device and Biopac device (reference device) during sitting and marking time and compared to verify the accuracy of R-R intervals. Second, the reliable data transmission to remote server was verified on two types of simulated emergency event using patient simulator. Third, during daily life with five types of motion, accuracy of data transmission to remote server was verified on two types of event occurring. By acquiring and comparing subject's biomedical signal and motion signal, the accuracy, reliability and operability, applicability during daily life of the developed device were verified. Therefore, cellular phone network based portable ECG device can monitor patient with inobtrusive manner. PMID:19162767

  5. Assessing Special Events.

    ERIC Educational Resources Information Center

    Neff, Bonita Dostal

    Special events defined as being "newsworthy events" are becoming a way of American life. They are also a means for making a lot of money. Examples of special events that are cited most frequently are often the most minor of events; e.g., the open house, the new business opening day gala, or a celebration of some event in an organization. Little…

  6. Screening for adverse events.

    PubMed

    Karson, A S; Bates, D W

    1999-02-01

    Adverse events (AEs) in medical patients are common, costly, and often preventable. Development of quality improvement programs to decrease the number and impact of AEs demands effective methods for screening for AEs on a routine basis. Here we describe the impact, types, and potential causes of AEs and review various techniques for identifying AEs. We evaluate the use of generic screening criteria in detail and describe a recent study of the sensitivity and specificity of individual generic screening criteria and combinations of these criteria. In general, the most sensitive screens were the least specific and no small sub-set of screens identified a large percentage of adverse events. Combinations of screens that were limited to administrative data were the least expensive, but none were particularly sensitive, although in practice they might be effective since routine screening is currently rarely done. As computer systems increase in sophistication sensitivity will improve. We also discuss recent studies that suggest that programs that screen for and identify AEs can be useful in reducing AE rates. While tools for identifying AEs have strengths and weaknesses, they can play an important role in organizations' quality improvement portfolios. PMID:10468381

  7. Common Conditions in Newborns

    MedlinePlus

    ... Prenatal Baby Bathing & Skin Care Breastfeeding Crying & Colic Diapers & Clothing Feeding & Nutrition Preemie Sleep Teething & Tooth Care Toddler Preschool Gradeschool Teen Young Adult Healthy Children > Ages & Stages > Baby > Common Conditions in ...

  8. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2004-01-01

    Part of the 2003 industrial minerals review. The legislation, production, and consumption of common clay and shale are discussed. The average prices of the material and outlook for the market are provided.

  9. Genomic Data Commons launches

    Cancer.gov

    The Genomic Data Commons (GDC), a unified data system that promotes sharing of genomic and clinical data between researchers, launched today with a visit from Vice President Joe Biden to the operations center at the University of Chicago.

  10. Barry Commoner Assails Petrochemicals

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1973

    1973-01-01

    Discusses Commoner's ideas on the social value of the petrochemical industry and his suggestions for curtailment or elimination of its productive operation to produce a higher environmental quality for mankind at a relatively low loss in social benefit. (CC)

  11. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2011-01-01

    The article discusses the latest developments in the global common clay and shale industry, particularly in the U.S. It claims that common clay and shale is mainly used in the manufacture of heavy clay products like brick, flue tile and sewer pipe. The main producing states in the U.S. include North Carolina, New York and Oklahoma. Among the firms that manufacture clay and shale-based products are Mid America Brick & Structural Clay Products LLC and Boral USA.

  12. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2006-01-01

    At present, 150 companies produce common clay and shale in 41 US states. According to the United States Geological Survey (USGS), domestic production in 2005 reached 24.8 Mt valued at $176 million. In decreasing order by tonnage, the leading producer states include North Carolina, Texas, Alabama, Georgia and Ohio. For the whole year, residential and commercial building construction remained the major market for common clay and shale products such as brick, drain tile, lightweight aggregate, quarry tile and structural tile.

  13. Crystallization kinetics and self-induced pinning in cellular patterns

    SciTech Connect

    Aranson, Igor S.; Malomed, Boris A.; Pismen, Len M.; Tsimring, Lev S.

    2000-07-01

    Within the framework of the Swift-Hohenberg model it is shown numerically and analytically that the front propagation between cellular and uniform states is determined by periodic nucleation events triggered by the explosive growth of the localized zero-eigenvalue mode of the corresponding linear problem. We derive an evolution equation for this mode using asymptotic analysis, and evaluate the time interval between nucleation events, and hence the front speed. In the presence of noise, we find the velocity exponent of ''thermally activated'' front propagation (creep) beyond the pinning threshold. (c) 2000 The American Physical Society.

  14. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 47 Telecommunication 2 2013-10-01 2013-10-01 false Cellular unserved area radiotelephone licenses subject to competitive bidding. 22.960 Section 22.960 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960...

  15. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 2 2012-10-01 2012-10-01 false Cellular unserved area radiotelephone licenses subject to competitive bidding. 22.960 Section 22.960 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960...

  16. 47 CFR 22.929 - Application requirements for the Cellular Radiotelephone Service.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.929 Application... 47 Telecommunication 2 2013-10-01 2013-10-01 false Application requirements for the Cellular... radiated power in each of the cardinal radial directions. (b) If the application involves a service...

  17. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 2 2011-10-01 2011-10-01 false Cellular unserved area radiotelephone licenses subject to competitive bidding. 22.960 Section 22.960 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960...

  18. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 2 2014-10-01 2014-10-01 false Cellular unserved area radiotelephone licenses subject to competitive bidding. 22.960 Section 22.960 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960...

  19. 47 CFR 22.960 - Cellular unserved area radiotelephone licenses subject to competitive bidding.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 2 2010-10-01 2010-10-01 false Cellular unserved area radiotelephone licenses subject to competitive bidding. 22.960 Section 22.960 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Cellular Radiotelephone Service § 22.960...

  20. Event Segmentation Ability Uniquely Predicts Event Memory

    PubMed Central

    Sargent, Jesse Q.; Zacks, Jeffrey M.; Hambrick, David Z.; Zacks, Rose T.; Kurby, Christopher A.; Bailey, Heather R.; Eisenberg, Michelle L.; Beck, Taylor M.

    2013-01-01

    Memory for everyday events plays a central role in tasks of daily living, autobiographical memory, and planning. Event memory depends in part on segmenting ongoing activity into meaningful units. This study examined the relationship between event segmentation and memory in a lifespan sample to answer the following question: Is the ability to segment activity into meaningful events a unique predictor of subsequent memory, or is the relationship between event perception and memory accounted for by general cognitive abilities? Two hundred and eight adults ranging from 20 to 79 years old segmented movies of everyday events and attempted to remember the events afterwards. They also completed psychometric ability tests and tests measuring script knowledge for everyday events. Event segmentation and script knowledge both explained unique variance in event memory above and beyond the psychometric measures, and did so as strongly in older as in younger adults. These results suggest that event segmentation is a basic cognitive mechanism, important for memory across the lifespan. PMID:23942350

  1. Biological (molecular and cellular) markers of toxicity

    SciTech Connect

    Shugart, L.R.

    1990-10-01

    The overall objective of this study is to evaluate the use of the small aquarium fish, Japanese Medaka (Oryzias latipes), as a predictor of potential genotoxicity following exposure to carcinogens. This will be accomplished by quantitatively investigating the early molecular events associated with genotoxicity of various tissues of Medaka subsequent to exposure of the organism to several known carcinogens, such as diethylnitrosamine (DEN) and benzo(a)pyrene (BaP). Because of the often long latent period between initial contact with certain chemical and physical agents in our environment and subsequent expression of deleterious health or ecological impact, the development of sensitive methods for detecting and estimating early exposure is needed so that necessary interventions can ensue. A promising biological endpoint for detecting early exposure to damaging chemicals is the interaction of these compounds with cellular macromolecules such as Deoxyribonucleic acids (DNA). This biological endpoint assumes significance because it can be one of the critical early events leading eventually to adverse effects (neoplasia) in the exposed organism.

  2. Flexible substrata for the detection of cellular traction forces

    NASA Technical Reports Server (NTRS)

    Beningo, Karen A.; Wang, Yu-Li

    2002-01-01

    By modulating adhesion signaling and cytoskeletal organization, mechanical forces play an important role in various cellular functions, from propelling cell migration to mediating communication between cells. Recent developments have resulted in several new approaches for the detection, analysis and visualization of mechanical forces generated by cultured cells. Combining these methods with other approaches, such as green-fluorescent protein (GFP) imaging and gene manipulation, proves to be particularly powerful for analyzing the interplay between extracellular physical forces and intracellular chemical events.

  3. Rhabdomyosarcoma: Advances in Molecular and Cellular Biology

    PubMed Central

    Sun, Xin; Guo, Wei; Shen, Jacson K.; Mankin, Henry J.; Hornicek, Francis J.; Duan, Zhenfeng

    2015-01-01

    Rhabdomyosarcoma (RMS) is the most common soft tissue malignancy in childhood and adolescence. The two major histological subtypes of RMS are alveolar RMS, driven by the fusion protein PAX3-FKHR or PAX7-FKHR, and embryonic RMS, which is usually genetically heterogeneous. The prognosis of RMS has improved in the past several decades due to multidisciplinary care. However, in recent years, the treatment of patients with metastatic or refractory RMS has reached a plateau. Thus, to improve the survival rate of RMS patients and their overall well-being, further understanding of the molecular and cellular biology of RMS and identification of novel therapeutic targets are imperative. In this review, we describe the most recent discoveries in the molecular and cellular biology of RMS, including alterations in oncogenic pathways, miRNA (miR), in vivo models, stem cells, and important signal transduction cascades implicated in the development and progression of RMS. Furthermore, we discuss novel potential targeted therapies that may improve the current treatment of RMS. PMID:26420980

  4. Cellular factors implicated in filovirus entry.

    PubMed

    Bhattacharyya, Suchita; Hope, Thomas J

    2013-01-01

    Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. PMID:23365575

  5. Sialidases as regulators of bioengineered cellular surfaces

    PubMed Central

    Zamora, Cristina Y; Ryan, Matthew J; d'Alarcao, Marc; Kumar, Krishna

    2015-01-01

    Human sialidases (NEUs) catalyze the removal of N-acetyl neuraminic acids from the glycome of the cell and regulate a diverse repertoire of nominal cellular functions, such as cell signaling and adhesion. A greater understanding of their substrate permissivity is of interest in order to discern their physiological functions in disease states and in the design of specific and effective small molecule inhibitors. Towards this, we have synthesized soluble fluorogenic reporters of mammalian sialidase activity bearing unnatural sialic acids commonly incorporated into the cellular glycocalyx via metabolic glycoengineering. We found cell-surface sialidases in Jurkat capable of cleaving unnatural sialic acids with differential activities toward a variety of R groups on neuraminic acid. In addition, we observed modulated structure–activity relationships when cell-surface sialidases were presented glycans with unnatural bulky, hydrophobic or fluorinated moieties incorporated directly via glycoengineering. Our results confirm the importance of cell-surface sialidases in glycoengineering incorporation data. We demonstrate the flexibility of human NEUs toward derivatized sugars and highlight the importance of native glycan presentation to sialidase binding and activity. These results stand to inform not only metabolic glycoengineering efforts but also inhibitor design. PMID:25795684

  6. Wrinkling in Cellular Structured Composites

    NASA Astrophysics Data System (ADS)

    Kaynia, Narges; Li, Yaning; Boyce, Mary C.

    2013-03-01

    Many structured composites found in nature possess undulating and wrinkled interfacial layers that regulate mechanical, chemical, acoustic, adhesive, thermal, electrical and optical functions of the material. This research focused on the formation of wrinkling patterns in cellular structured composites and the effect of the wrinkling pattern on the overall structural response. The cellular composites consisted of stiffer interfacial layers constructing a network submerged in a soft matrix. Analytical and finite element models were developed to capture various aspects of the wrinkling mechanism. The characteristics of the undulation patterns and the instability modes were investigated as functions of model geometry and material composition. Mechanical experiments were designed to further explore the modeling results. The cellular composite samples were fabricated by using different types of elastomers and by varying the geometry and the material properties. The experimental and numerical results were consistent with the analytical predictions. The results in this research improve understanding of the mechanisms governing the undulation pattern formation in cellular composites and can be used to enable on-demand tunability of different functions to provide, among others, active control of wave propagation, mechanical stiffness and deformation, and material swelling and growth.

  7. Cellular Automata and the Humanities.

    ERIC Educational Resources Information Center

    Gallo, Ernest

    1994-01-01

    The use of cellular automata to analyze several pre-Socratic hypotheses about the evolution of the physical world is discussed. These hypotheses combine characteristics of both rigorous and metaphoric language. Since the computer demands explicit instructions for each step in the evolution of the automaton, such models can reveal conceptual…

  8. Developing an effective 2-D urban flood inundation model for city emergency management based on cellular automata

    NASA Astrophysics Data System (ADS)

    Liu, L.; Liu, Y.; Wang, X.; Yu, D.; Liu, K.; Huang, H.; Hu, G.

    2014-09-01

    Flash floods have occurred frequently and severely in the urban areas of South China. An effective process-oriented urban flood inundation model becomes an urgent demand for urban storm water and emergency management. This study develops an effective and flexible cellular automaton (CA) model to simulate storm water runoff and the flood inundation process during extreme storm events. The process of infiltration, inlets discharge and flow dynamic can be simulated only with little pre-processing on commonly available basic urban geographic data. In this model, a set of gravitational diverging rules are implemented in a cellular automation (CA) model to govern the water flow in a 3 x 3 cell template of a raster layer. The model is calibrated by one storm event and validated by another in a small urban catchment in Guangzhou of Southern China. The depth of accumulated water at the catchment outlet is interpreted from street monitoring sensors and verified by on-site survey. A good level of agreement between the simulated process and the reality is reached for both storm events. The model reproduces the changing extent and depth of flooded areas at the catchment outlet with an accuracy of 4 cm in water depth. Comparisons with a physically-based 2-D model (FloodMap) results show that the model have the capability of simulating flow dynamics. The high computational efficiency of CA model can satisfy the demand of city emergency management. The encouraging results of the simulations demonstrate that the CA-based approach is capable of effectively representing the key processes associated with a storm event and reproducing the process of water accumulation at the catchment outlet for making process-considered city emergency management decisions.

  9. Event-Based Science.

    ERIC Educational Resources Information Center

    Wright, Russell G.

    1992-01-01

    Suggests that an event-based science curriculum can provide the framework for deciding what to retain in an overloaded science curriculum. Provides examples of current events and the science concepts explored related to the event. (MDH)

  10. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant

    PubMed Central

    Bensoussan, Nicolas; Santamaria, M. Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding. PMID:27512397

  11. Plant-Herbivore Interaction: Dissection of the Cellular Pattern of Tetranychus urticae Feeding on the Host Plant.

    PubMed

    Bensoussan, Nicolas; Santamaria, M Estrella; Zhurov, Vladimir; Diaz, Isabel; Grbić, Miodrag; Grbić, Vojislava

    2016-01-01

    The two-spotted spider mite, Tetranychus urticae Koch (Acari: Tetranychidae), is one of the most polyphagous herbivores feeding on cell contents of over 1100 plant species including more than 150 crops. It is being established as a model for chelicerate herbivores with tools that enable tracking of reciprocal responses in plant-spider mite interactions. However, despite their important pest status and a growing understanding of the molecular basis of interactions with plant hosts, knowledge of the way mites interface with the plant while feeding and the plant damage directly inflicted by mites is lacking. Here, utilizing histology and microscopy methods, we uncovered several key features of T. urticae feeding. By following the stylet path within the plant tissue, we determined that the stylet penetrates the leaf either in between epidermal pavement cells or through a stomatal opening, without damaging the epidermal cellular layer. Our recordings of mite feeding established that duration of the feeding event ranges from several minutes to more than half an hour, during which time mites consume a single mesophyll cell in a pattern that is common to both bean and Arabidopsis plant hosts. In addition, this study determined that leaf chlorotic spots, a common symptom of mite herbivory, do not form as an immediate consequence of mite feeding. Our results establish a cellular context for the plant-spider mite interaction that will support our understanding of the molecular mechanisms and cell signaling associated with spider mite feeding. PMID:27512397

  12. Power system commonality study

    NASA Astrophysics Data System (ADS)

    Littman, Franklin D.

    1992-07-01

    A limited top level study was completed to determine the commonality of power system/subsystem concepts within potential lunar and Mars surface power system architectures. A list of power system concepts with high commonality was developed which can be used to synthesize power system architectures which minimize development cost. Examples of potential high commonality power system architectures are given in this report along with a mass comparison. Other criteria such as life cycle cost (which includes transportation cost), reliability, safety, risk, and operability should be used in future, more detailed studies to select optimum power system architectures. Nineteen potential power system concepts were identified and evaluated for planetary surface applications including photovoltaic arrays with energy storage, isotope, and nuclear power systems. A top level environmental factors study was completed to assess environmental impacts on the identified power system concepts for both lunar and Mars applications. Potential power system design solutions for commonality between Mars and lunar applications were identified. Isotope, photovoltaic array (PVA), regenerative fuel cell (RFC), stainless steel liquid-metal cooled reactors (less than 1033 K maximum) with dynamic converters, and in-core thermionic reactor systems were found suitable for both lunar and Mars environments. The use of SP-100 thermoelectric (TE) and SP-100 dynamic power systems in a vacuum enclosure may also be possible for Mars applications although several issues need to be investigated further (potential single point failure of enclosure, mass penalty of enclosure and active pumping system, additional installation time and complexity). There are also technical issues involved with development of thermionic reactors (life, serviceability, and adaptability to other power conversion units). Additional studies are required to determine the optimum reactor concept for Mars applications. Various screening

  13. Common Cause Failure Modes

    NASA Technical Reports Server (NTRS)

    Wetherholt, Jon; Heimann, Timothy J.; Anderson, Brenda

    2011-01-01

    High technology industries with high failure costs commonly use redundancy as a means to reduce risk. Redundant systems, whether similar or dissimilar, are susceptible to Common Cause Failures (CCF). CCF is not always considered in the design effort and, therefore, can be a major threat to success. There are several aspects to CCF which must be understood to perform an analysis which will find hidden issues that may negate redundancy. This paper will provide definition, types, a list of possible causes and some examples of CCF. Requirements and designs from NASA projects will be used in the paper as examples.

  14. Cellular senescence in the Penna model of aging

    NASA Astrophysics Data System (ADS)

    Periwal, Avikar

    2013-11-01

    Cellular senescence is thought to play a major role in age-related diseases, which cause nearly 67% of all human deaths worldwide. Recent research in mice showed that exercising mice had higher levels of telomerase, an enzyme that helps maintain telomere length, than nonexercising mice. A commonly used model for biological aging was proposed by Penna. I propose a modification of the Penna model that incorporates cellular senescence and find an analytical steady-state solution following Coe, Mao, and Cates [Phys. Rev. Lett.PRLTAO0031-900710.1103/PhysRevLett.89.288103 89, 288103 (2002)]. I find that models corresponding to delayed cellular senescence have younger populations that live longer. I fit the model to the United Kingdom's death distribution, which the original Penna model cannot do.

  15. Common Magnets, Unexpected Polarities

    ERIC Educational Resources Information Center

    Olson, Mark

    2013-01-01

    In this paper, I discuss a "misconception" in magnetism so simple and pervasive as to be typically unnoticed. That magnets have poles might be considered one of the more straightforward notions in introductory physics. However, the magnets common to students' experiences are likely different from those presented in educational…

  16. Solving Common Mathematical Problems

    NASA Technical Reports Server (NTRS)

    Luz, Paul L.

    2005-01-01

    Mathematical Solutions Toolset is a collection of five software programs that rapidly solve some common mathematical problems. The programs consist of a set of Microsoft Excel worksheets. The programs provide for entry of input data and display of output data in a user-friendly, menu-driven format, and for automatic execution once the input data has been entered.

  17. Information Commons to Go

    ERIC Educational Resources Information Center

    Bayer, Marc Dewey

    2008-01-01

    Since 2004, Buffalo State College's E. H. Butler Library has used the Information Commons (IC) model to assist its 8,500 students with library research and computer applications. Campus Technology Services (CTS) plays a very active role in its IC, with a centrally located Computer Help Desk and a newly created Application Support Desk right in the…

  18. Common Carrier Services.

    ERIC Educational Resources Information Center

    Federal Communications Commission, Washington, DC.

    After outlining the Federal Communications Commission's (FCC) responsibility for regulating interstate common carrier communication (non-broadcast communication whose carriers are required by law to furnish service at reasonable charges upon request), this information bulletin reviews the history, technological development, and current…

  19. Common Carrier Services.

    ERIC Educational Resources Information Center

    Federal Communications Commission, Washington, DC.

    This bulletin outlines the Federal Communications Commission's (FCC) responsibilities in regulating the interstate and foreign common carrier communication via electrical means. Also summarized are the history, technological development, and current capabilities and prospects of telegraph, wire telephone, radiotelephone, satellite communications,…

  20. Human Commonalities and Art

    ERIC Educational Resources Information Center

    Passmore, Kaye

    2008-01-01

    Educator Ernest Boyer believed that well-educated students should do more than master isolated facts. They should understand the "connectedness of things." He suggested organizing curriculum thematically around eight commonalities shared by people around the world. In the book "The Basic School: A Community for Learning," Boyer recommends that…

  1. Common conversion factors.

    PubMed

    2001-05-01

    This appendix presents tables of some of the more common conversion factors for units of measure used throughout Current Protocols manuals, as well as prefixes indicating powers of ten for SI units. Another table gives conversions between temperatures on the Celsius (Centigrade) and Fahrenheit scales. PMID:18770653

  2. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2001-01-01

    Part of the 2000 annual review of the industrial minerals sector. A general overview of the common clay and shale industry is provided. In 2000, U.S. production increased by 5 percent, while sales or use declined to 23.6 Mt. Despite the slowdown in the economy, no major changes are expected for the market.

  3. Common clay and shale

    USGS Publications Warehouse

    Virta, R.L.

    2003-01-01

    Part of the 2002 industrial minerals review. The production, consumption, and price of shale and common clay in the U.S. during 2002 are discussed. The impact of EPA regulations on brick and structural clay product manufacturers is also outlined.

  4. Common file formats.

    PubMed

    Leonard, Shonda A; Littlejohn, Timothy G; Baxevanis, Andreas D

    2007-01-01

    This appendix discusses a few of the file formats frequently encountered in bioinformatics. Specifically, it reviews the rules for generating FASTA files and provides guidance for interpreting NCBI descriptor lines, commonly found in FASTA files. In addition, it reviews the construction of GenBank, Phylip, MSF and Nexus files. PMID:18428774

  5. Navagating the Common Core

    ERIC Educational Resources Information Center

    McShane, Michael Q.

    2014-01-01

    This article presents a debate over the Common Core State Standards Initiative as it has rocketed to the forefront of education policy discussions around the country. The author contends that there is value in having clear cross state standards that will clarify the new online and blended learning that the growing use of technology has provided…

  6. The Common Denominator

    ERIC Educational Resources Information Center

    Grimes, Nikki

    2005-01-01

    An author and a poet Nikki Grimes uses her art to reach across differences such as race and culture, and show the commonality of human experience. She uses the power of her poetry to break down racial barriers, shatter cultural stereotypes, and forge community.

  7. Mathematics: Common Curriculum Goals.

    ERIC Educational Resources Information Center

    Oregon State Dept. of Education, Salem.

    This document defines what are considered to be the essentials in a strong mathematics program for the state of Oregon for grades K-12. The common curriculum goals are organized into nine content strands: (1) number and numeration; (2) appropriate computational skills; (3) problem solving; (4) geometry and visualization skills; (5) measurement;…

  8. Common Dermatoses of Infancy

    PubMed Central

    Gora, Irv

    1986-01-01

    Within the pediatric population of their practices, family physicians frequently encounter infants with skin rashes. This article discusses several of the more common rashes of infancy: atopic dermatitis, cradle cap, diaper dermatitis and miliaria. Etiology, clinical picture and possible approaches to treatment are presented. ImagesFigure 1Figure 2Figure 3Figure 4Figure 5Figure 6Figure 7 PMID:21267297

  9. Space station commonality analysis

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This study was conducted on the basis of a modification to Contract NAS8-36413, Space Station Commonality Analysis, which was initiated in December, 1987 and completed in July, 1988. The objective was to investigate the commonality aspects of subsystems and mission support hardware while technology experiments are accommodated on board the Space Station in the mid-to-late 1990s. Two types of mission are considered: (1) Advanced solar arrays and their storage; and (2) Satellite servicing. The point of departure for definition of the technology development missions was a set of missions described in the Space Station Mission Requirements Data Base. (MRDB): TDMX 2151 Solar Array/Energy Storage Technology; TDMX 2561 Satellite Servicing and Refurbishment; TDMX 2562 Satellite Maintenance and Repair; TDMX 2563 Materials Resupply (to a free-flyer materials processing platform); TDMX 2564 Coatings Maintenance Technology; and TDMX 2565 Thermal Interface Technology. Issues to be addressed according to the Statement of Work included modularity of programs, data base analysis interactions, user interfaces, and commonality. The study was to consider State-of-the-art advances through the 1990s and to select an appropriate scale for the technology experiments, considering hardware commonality, user interfaces, and mission support requirements. The study was to develop evolutionary plans for the technology advancement missions.

  10. Common Standards for All

    ERIC Educational Resources Information Center

    Principal, 2010

    2010-01-01

    About three-fourths of the states have already adopted the Common Core State Standards, which were designed to provide more clarity about and consistency in what is expected of student learning across the country. However, given the brief time since the standards' final release in June, questions persist among educators, who will have the…

  11. Thermodynamics of cellular statistical inference

    NASA Astrophysics Data System (ADS)

    Lang, Alex; Fisher, Charles; Mehta, Pankaj

    2014-03-01

    Successful organisms must be capable of accurately sensing the surrounding environment in order to locate nutrients and evade toxins or predators. However, single cell organisms face a multitude of limitations on their accuracy of sensing. Berg and Purcell first examined the canonical example of statistical limitations to cellular learning of a diffusing chemical and established a fundamental limit to statistical accuracy. Recent work has shown that the Berg and Purcell learning limit can be exceeded using Maximum Likelihood Estimation. Here, we recast the cellular sensing problem as a statistical inference problem and discuss the relationship between the efficiency of an estimator and its thermodynamic properties. We explicitly model a single non-equilibrium receptor and examine the constraints on statistical inference imposed by noisy biochemical networks. Our work shows that cells must balance sample number, specificity, and energy consumption when performing statistical inference. These tradeoffs place significant constraints on the practical implementation of statistical estimators in a cell.

  12. Optofluidic Detection for Cellular Phenotyping

    PubMed Central

    Tung, Yi-Chung; Huang, Nien-Tsu; Oh, Bo-Ram; Patra, Bishnubrata; Pan, Chi-Chun; Qiu, Teng; Paul, K. Chu; Zhang, Wenjun; Kurabayashi, Katsuo

    2012-01-01

    Quantitative analysis of the output of processes and molecular interactions within a single cell is highly critical to the advancement of accurate disease screening and personalized medicine. Optical detection is one of the most broadly adapted measurement methods in biological and clinical assays and serves cellular phenotyping. Recently, microfluidics has obtained increasing attention due to several advantages, such as small sample and reagent volumes, very high throughput, and accurate flow control in the spatial and temporal domains. Optofluidics, which is the attempt to integrate optics with microfluidic, shows great promise to enable on-chip phenotypic measurements with high precision, sensitivity, specificity, and simplicity. This paper reviews the most recent developments of optofluidic technologies for cellular phenotyping optical detection. PMID:22854915

  13. Hox Targets and Cellular Functions

    PubMed Central

    Sánchez-Herrero, Ernesto

    2013-01-01

    Hox genes are a group of genes that specify structures along the anteroposterior axis in bilaterians. Although in many cases they do so by modifying a homologous structure with a different (or no) Hox input, there are also examples of Hox genes constructing new organs with no homology in other regions of the body. Hox genes determine structures though the regulation of targets implementing cellular functions and by coordinating cell behavior. The genetic organization to construct or modify a certain organ involves both a genetic cascade through intermediate transcription factors and a direct regulation of targets carrying out cellular functions. In this review I discuss new data from genome-wide techniques, as well as previous genetic and developmental information, to describe some examples of Hox regulation of different cell functions. I also discuss the organization of genetic cascades leading to the development of new organs, mainly using Drosophila melanogaster as the model to analyze Hox function. PMID:24490109

  14. Peroxisome Metabolism and Cellular Aging

    PubMed Central

    Titorenko, Vladimir I.; Terlecky, Stanley R.

    2010-01-01

    The essential role of peroxisomes in fatty acid oxidation, anaplerotic metabolism, and hydrogen peroxide turnover is well established. Recent findings suggest these and other related biochemical processes governed by the organelle may also play a critical role in regulating cellular aging. The goal of this review is to summarize and integrate into a model, the evidence that peroxisome metabolism actually helps define the replicative and chronological age of a eukaryotic cell. In this model, peroxisomal reactive oxygen species (ROS) are seen as altering organelle biogenesis and function, and eliciting changes in the dynamic communication networks that exist between peroxisomes and other cellular compartments. At low levels, peroxisomal ROS activate an anti-aging program in the cell; at concentrations beyond a specific threshold, a pro-aging course is triggered. PMID:21083858

  15. Cellular solidification of transparent monotectics

    NASA Technical Reports Server (NTRS)

    Kaulker, W. F.

    1986-01-01

    Understanding how liquid phase particles are engulfed or pushed during freezing of a monotectic is addressed. The additional complication is that the solid-liquid interface is nonplanar due to constitutional undercooling. Some evidence of particle pushing where the particles are the liquid phase of the montectic was already observed. Cellular freezing of the succinonitrile-glycerol system also occurred. Only a few compositions were tested at that time. The starting materials were not especially pure so that cellular interface observed was likely due to the presence of unkown impurities, the major portion of which was water. Topics addressed include: the effort of modeling the particle pushing process using the computer, establishing an apparatus for the determination of phase diagrams, and the measurement of the temperature gradients with a specimen which will solidify on the temperature gradient microscope stage.

  16. Xtoys: Cellular automata on xwindows

    SciTech Connect

    Creutz, M.

    1995-08-15

    Xtoys is a collection of xwindow programs for demonstrating simulations of various statistical models. Included are xising, for the two dimensional Ising model, xpotts, for the q-state Potts model, xautomalab, for a fairly general class of totalistic cellular automata, xsand, for the Bak-Tang-Wiesenfield model of self organized criticality, and xfires, a simple forest fire simulation. The programs should compile on any machine supporting xwindows.

  17. Molecular and cellular mechanisms of cardiotoxicity.

    PubMed Central

    Kang, Y J

    2001-01-01

    Cardiotoxicity resulting from detrimental environmental insults has been recognized for a long time. However, extensive studies of the mechanisms involved had not been undertaken until recent years. Advances in molecular biology provide powerful tools and make such studies possible. We are gathering information about cellular events, signaling pathways, and molecular mechanisms of myocardial toxicologic responses to environmental toxicants and pollutants. Severe acute toxic insults cause cardiac cell death instantly. In the early response to mild environmental stimuli, biochemical changes such as alterations in calcium homeostasis occur. These may lead to cardiac arrhythmia, which most often is reversible. Prolonged stimuli activate transcription factors such as activator protein-1 through elevation of intracellular calcium and the subsequent activation of calcineurin. Upregulation by activated transcription factors of hypertrophic genes results in heart hypertrophy, which is a short-term adaptive response to detrimental factors. However, further development of hypertrophy will lead to severe and irreversible cardiomyopathy, and eventually heart failure. From cardiac hypertrophy to heart failure, myocardial cells undergo extensive biochemical and molecular changes. Cardiac hypertrophy causes tissue hypoperfusion, which activates compensatory mechanisms such as production of angiotensin II and norepinephrine. Both further stimulate cardiac hypertrophy and, importantly, activate counterregulatory mechanisms including overexpression of atrial natriuretic peptide and b-type natriuretic peptide, and production of cytokines such as tumor necrosis factor-alpha. This counterregulation leads to myocardial remodeling as well as cell death through apoptosis and necrosis. Cell death through activation of mitochondrial factors and other pathways constitutes an important cellular mechanism of heart failure. Our current knowledge of cardiotoxicity is limited. Further extensive

  18. Competitive potential of cellular mobile telecommunications

    SciTech Connect

    Ware, H.

    1983-02-03

    The Federal Communications Commission (FCC) has recently issued rules for the commercial operation of a telecommunications technology not previously in commercial use: the cellular mobile radio. The author has carefully considered the potential for competition between cellular systems and for competition between cellular radio and alternative communications technologies under the regulatory scheme which has been adopted by the FCC. He finds that competition between cellular and wire-line services can be viable if cellular cost and demand data are carefully tracked to avoid market congestion and if cellular or other techniques are not allowed to undercut selected local exchange rates.

  19. Simulation Modeling by Classification of Problems: A Case of Cellular Manufacturing

    NASA Astrophysics Data System (ADS)

    Afiqah, K. N.; Mahayuddin, Z. R.

    2016-02-01

    Cellular manufacturing provides good solution approach to manufacturing area by applying Group Technology concept. The evolution of cellular manufacturing can enhance performance of the cell and to increase the quality of the product manufactured but it triggers other problem. Generally, this paper highlights factors and problems which emerge commonly in cellular manufacturing. The aim of the research is to develop a thorough understanding of common problems in cellular manufacturing. A part from that, in order to find a solution to the problems exist using simulation technique, this classification framework is very useful to be adapted during model building. Biology evolution tool was used in the research in order to classify the problems emerge. The result reveals 22 problems and 25 factors using cladistic technique. In this research, the expected result is the cladogram established based on the problems in cellular manufacturing gathered.

  20. Evolutionary tradeoffs in cellular composition across diverse bacteria.

    PubMed

    Kempes, Christopher P; Wang, Lawrence; Amend, Jan P; Doyle, John; Hoehler, Tori

    2016-09-01

    One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content-the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components. PMID:27046336

  1. Evolutionary tradeoffs in cellular composition across diverse bacteria

    PubMed Central

    Kempes, Christopher P; Wang, Lawrence; Amend, Jan P; Doyle, John; Hoehler, Tori

    2016-01-01

    One of the most important classic and contemporary interests in biology is the connection between cellular composition and physiological function. Decades of research have allowed us to understand the detailed relationship between various cellular components and processes for individual species, and have uncovered common functionality across diverse species. However, there still remains the need for frameworks that can mechanistically predict the tradeoffs between cellular functions and elucidate and interpret average trends across species. Here we provide a comprehensive analysis of how cellular composition changes across the diversity of bacteria as connected with physiological function and metabolism, spanning five orders of magnitude in body size. We present an analysis of the trends with cell volume that covers shifts in genomic, protein, cellular envelope, RNA and ribosomal content. We show that trends in protein content are more complex than a simple proportionality with the overall genome size, and that the number of ribosomes is simply explained by cross-species shifts in biosynthesis requirements. Furthermore, we show that the largest and smallest bacteria are limited by physical space requirements. At the lower end of size, cell volume is dominated by DNA and protein content—the requirement for which predicts a lower limit on cell size that is in good agreement with the smallest observed bacteria. At the upper end of bacterial size, we have identified a point at which the number of ribosomes required for biosynthesis exceeds available cell volume. Between these limits we are able to discuss systematic and dramatic shifts in cellular composition. Much of our analysis is connected with the basic energetics of cells where we show that the scaling of metabolic rate is surprisingly superlinear with all cellular components. PMID:27046336

  2. Noncommuting local common causes for correlations violating the Clauser-Horne inequality

    SciTech Connect

    Hofer-Szabo, Gabor; Vecsernyes, Peter

    2012-12-15

    In the paper, the EPR-Bohm scenario will be reproduced in an algebraic quantum field theoretical setting with locally finite degrees of freedom. It will be shown that for a set of spatially separated correlating events (projections) maximally violating the Clauser-Horne inequality there can be given a common causal explanation if commutativity is abandoned between the common cause and the correlating events. Moreover, the noncommuting common cause will be local and supported in the common past of the correlating events.

  3. ATR inhibition rewires cellular signaling networks induced by replication stress.

    PubMed

    Wagner, Sebastian A; Oehler, Hannah; Voigt, Andrea; Dalic, Denis; Freiwald, Anja; Serve, Hubert; Beli, Petra

    2016-02-01

    The slowing down or stalling of replication forks is commonly known as replication stress and arises from multiple causes such as DNA lesions, nucleotide depletion, RNA-DNA hybrids, and oncogene activation. The ataxia telangiectasia and Rad3-related kinase (ATR) plays an essential role in the cellular response to replication stress and inhibition of ATR has emerged as therapeutic strategy for the treatment of cancers that exhibit high levels of replication stress. However, the cellular signaling induced by replication stress and the substrate spectrum of ATR has not been systematically investigated. In this study, we employed quantitative MS-based proteomics to define the cellular signaling after nucleotide depletion-induced replication stress and replication fork collapse following ATR inhibition. We demonstrate that replication stress results in increased phosphorylation of a subset of proteins, many of which are involved in RNA splicing and transcription and have previously not been associated with the cellular replication stress response. Furthermore, our data reveal the ATR-dependent phosphorylation following replication stress and discover novel putative ATR target sites on MCM6, TOPBP1, RAD51AP1, and PSMD4. We establish that ATR inhibition rewires cellular signaling networks induced by replication stress and leads to the activation of the ATM-driven double-strand break repair signaling. PMID:26572502

  4. Molecular paleontology and complexity in the last eukaryotic common ancestor

    PubMed Central

    Koumandou, V. Lila; Wickstead, Bill; Ginger, Michael L.; van der Giezen, Mark; Dacks, Joel B.

    2013-01-01

    Eukaryogenesis, the origin of the eukaryotic cell, represents one of the fundamental evolutionary transitions in the history of life on earth. This event, which is estimated to have occurred over one billion years ago, remains rather poorly understood. While some well-validated examples of fossil microbial eukaryotes for this time frame have been described, these can provide only basic morphology and the molecular machinery present in these organisms has remained unknown. Complete and partial genomic information has begun to fill this gap, and is being used to trace proteins and cellular traits to their roots and to provide unprecedented levels of resolution of structures, metabolic pathways and capabilities of organisms at these earliest points within the eukaryotic lineage. This is essentially allowing a molecular paleontology. What has emerged from these studies is spectacular cellular complexity prior to expansion of the eukaryotic lineages. Multiple reconstructed cellular systems indicate a very sophisticated biology, which by implication arose following the initial eukaryogenesis event but prior to eukaryotic radiation and provides a challenge in terms of explaining how these early eukaryotes arose and in understanding how they lived. Here, we provide brief overviews of several cellular systems and the major emerging conclusions, together with predictions for subsequent directions in evolution leading to extant taxa. We also consider what these reconstructions suggest about the life styles and capabilities of these earliest eukaryotes and the period of evolution between the radiation of eukaryotes and the eukaryogenesis event itself. PMID:23895660

  5. Common tester platform concept.

    SciTech Connect

    Hurst, Michael James

    2008-05-01

    This report summarizes the results of a case study on the doctrine of a common tester platform, a concept of a standardized platform that can be applicable across the broad spectrum of testing requirements throughout the various stages of a weapons program, as well as across the various weapons programs. The common tester concept strives to define an affordable, next-generation design that will meet testing requirements with the flexibility to grow and expand; supporting the initial development stages of a weapons program through to the final production and surveillance stages. This report discusses a concept investing key leveraging technologies and operational concepts combined with prototype tester-development experiences and practical lessons learned gleaned from past weapons programs.

  6. Commonly missed orthopedic problems.

    PubMed

    Ballas, M T; Tytko, J; Mannarino, F

    1998-01-15

    When not diagnosed early and managed appropriately, common musculoskeletal injuries may result in long-term disabling conditions. Anterior cruciate ligament tears are some of the most common knee ligament injuries. Slipped capital femoral epiphysis may present with little or no hip pain, and subtle or absent physical and radiographic findings. Femoral neck stress fractures, if left untreated, may result in avascular necrosis, refractures and pseudoarthrosis. A delay in diagnosis of scaphoid fractures may cause early wrist arthrosis if nonunion results. Ulnar collateral ligament tears are a frequently overlooked injury in skiers. The diagnosis of Achilles tendon rupture is missed as often as 25 percent of the time. Posterior tibial tendon tears may result in fixed bony planus if diagnosis is delayed, necessitating hindfoot fusion rather than simple soft tissue repair. Family physicians should be familiar with the initial assessment of these conditions and, when appropriate, refer patients promptly to an orthopedic surgeon. PMID:9456991

  7. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Rob; Novack, Steven D.

    2015-01-01

    Common Cause Failures (CCFs) are a known and documented phenomenon that defeats system redundancy. CCFS are a set of dependent type of failures that can be caused by: system environments; manufacturing; transportation; storage; maintenance; and assembly, as examples. Since there are many factors that contribute to CCFs, the effects can be reduced, but they are difficult to eliminate entirely. Furthermore, failure databases sometimes fail to differentiate between independent and CCF (dependent) failure and data is limited, especially for launch vehicles. The Probabilistic Risk Assessment (PRA) of NASA's Safety and Mission Assurance Directorate at Marshall Space Flight Center (MFSC) is using generic data from the Nuclear Regulatory Commission's database of common cause failures at nuclear power plants to estimate CCF due to the lack of a more appropriate data source. There remains uncertainty in the actual magnitude of the common cause risk estimates for different systems at this stage of the design. Given the limited data about launch vehicle CCF and that launch vehicles are a highly redundant system by design, it is important to make design decisions to account for a range of values for independent and CCFs. When investigating the design of the one-out-of-two component redundant system for launch vehicles, a response surface was constructed to represent the impact of the independent failure rate versus a common cause beta factor effect on a system's failure probability. This presentation will define a CCF and review estimation calculations. It gives a summary of reduction methodologies and a review of examples of historical CCFs. Finally, it presents the response surface and discusses the results of the different CCFs on the reliability of a one-out-of-two system.

  8. Common Cause Failure Modeling

    NASA Technical Reports Server (NTRS)

    Hark, Frank; Britton, Paul; Ring, Rob; Novack, Steven D.

    2016-01-01

    Common Cause Failures (CCFs) are a known and documented phenomenon that defeats system redundancy. CCFS are a set of dependent type of failures that can be caused by: system environments; manufacturing; transportation; storage; maintenance; and assembly, as examples. Since there are many factors that contribute to CCFs, the effects can be reduced, but they are difficult to eliminate entirely. Furthermore, failure databases sometimes fail to differentiate between independent and CCF (dependent) failure and data is limited, especially for launch vehicles. The Probabilistic Risk Assessment (PRA) of NASA's Safety and Mission Assurance Directorate at Marshal Space Flight Center (MFSC) is using generic data from the Nuclear Regulatory Commission's database of common cause failures at nuclear power plants to estimate CCF due to the lack of a more appropriate data source. There remains uncertainty in the actual magnitude of the common cause risk estimates for different systems at this stage of the design. Given the limited data about launch vehicle CCF and that launch vehicles are a highly redundant system by design, it is important to make design decisions to account for a range of values for independent and CCFs. When investigating the design of the one-out-of-two component redundant system for launch vehicles, a response surface was constructed to represent the impact of the independent failure rate versus a common cause beta factor effect on a system's failure probability. This presentation will define a CCF and review estimation calculations. It gives a summary of reduction methodologies and a review of examples of historical CCFs. Finally, it presents the response surface and discusses the results of the different CCFs on the reliability of a one-out-of-two system.

  9. Common drive unit

    NASA Technical Reports Server (NTRS)

    Ellis, R. C.; Fink, R. A.; Moore, E. A.

    1987-01-01

    The Common Drive Unit (CDU) is a high reliability rotary actuator with many versatile applications in mechanism designs. The CDU incorporates a set of redundant motor-brake assemblies driving a single output shaft through differential. Tachometers provide speed information in the AC version. Operation of both motors, as compared to the operation of one motor, will yield the same output torque with twice the output speed.

  10. Common Anorectal Disorders

    PubMed Central

    Foxx-Orenstein, Amy E.; Umar, Sarah B.; Crowell, Michael D.

    2014-01-01

    Anorectal disorders result in many visits to healthcare specialists. These disorders include benign conditions such as hemorrhoids to more serious conditions such as malignancy; thus, it is important for the clinician to be familiar with these disorders as well as know how to conduct an appropriate history and physical examination. This article reviews the most common anorectal disorders, including hemorrhoids, anal fissures, fecal incontinence, proctalgia fugax, excessive perineal descent, and pruritus ani, and provides guidelines on comprehensive evaluation and management. PMID:24987313

  11. Common Geometry Module

    Energy Science and Technology Software Center (ESTSC)

    2005-01-01

    The Common Geometry Module (CGM) is a code library which provides geometry functionality used for mesh generation and other applications. This functionality includes that commonly found in solid modeling engines, like geometry creation, query and modification; CGM also includes capabilities not commonly found in solid modeling engines, like geometry decomposition tools and support for shared material interfaces. CGM is built upon the ACIS solid modeling engine, but also includes geometry capability developed beside and onmore » top of ACIS. CGM can be used as-is to provide geometry functionality for codes needing this capability. However, CGM can also be extended using derived classes in C++, allowing the geometric model to serve as the basis for other applications, for example mesh generation. CGM is supported on Sun Solaris, SGI, HP, IBM, DEC, Linux and Windows NT platforms. CGM also indudes support for loading ACIS models on parallel computers, using MPI-based communication. Future plans for CGM are to port it to different solid modeling engines, including Pro/Engineer or SolidWorks. CGM is being released into the public domain under an LGPL license; the ACIS-based engine is available to ACIS licensees on request.« less

  12. Common HEP UNIX Environment

    NASA Astrophysics Data System (ADS)

    Taddei, Arnaud

    After it had been decided to design a common user environment for UNIX platforms among HEP laboratories, a joint project between DESY and CERN had been started. The project consists in 2 phases: 1. Provide a common user environment at shell level, 2. Provide a common user environment at graphical level (X11). Phase 1 is in production at DESY and at CERN as well as at PISA and RAL. It has been developed around the scripts originally designed at DESY Zeuthen improved and extended with a 2 months project at CERN with a contribution from DESY Hamburg. It consists of a set of files which are customizing the environment for the 6 main shells (sh, csh, ksh, bash, tcsh, zsh) on the main platforms (AIX, HP-UX, IRIX, SunOS, Solaris 2, OSF/1, ULTRIX, etc.) and it is divided at several "sociological" levels: HEP, site, machine, cluster, group of users and user with some levels which are optional. The second phase is under design and a first proposal has been published. A first version of the phase 2 exists already for AIX and Solaris, and it should be available for all other platforms, by the time of the conference. This is a major collective work between several HEP laboratories involved in the HEPiX-scripts and HEPiX-X11 working-groups.

  13. 'Historicising common sense'.

    PubMed

    Millstone, Noah

    2012-12-01

    This essay is an expanded set of comments on the social psychology papers written for the special issue on History and Social Psychology. It considers what social psychology, and particularly the theory of social representations, might offer historians working on similar problems, and what historical methods might offer social psychology. The social history of thinking has been a major theme in twentieth and twenty-first century historical writing, represented most recently by the genre of 'cultural history'. Cultural history and the theory of social representations have common ancestors in early twentieth-century social science. Nevertheless, the two lines of research have developed in different ways and are better seen as complementary than similar. The theory of social representations usefully foregrounds issues, like social division and change over time, that cultural history relegates to the background. But for historians, the theory of social representations seems oddly fixated on comparing the thought styles associated with positivist science and 'common sense'. Using historical analysis, this essay tries to dissect the core opposition 'science : common sense' and argues for a more flexible approach to comparing modes of thought. PMID:23135802

  14. Bayesian analysis of rare events

    NASA Astrophysics Data System (ADS)

    Straub, Daniel; Papaioannou, Iason; Betz, Wolfgang

    2016-06-01

    In many areas of engineering and science there is an interest in predicting the probability of rare events, in particular in applications related to safety and security. Increasingly, such predictions are made through computer models of physical systems in an uncertainty quantification framework. Additionally, with advances in IT, monitoring and sensor technology, an increasing amount of data on the performance of the systems is collected. This data can be used to reduce uncertainty, improve the probability estimates and consequently enhance the management of rare events and associated risks. Bayesian analysis is the ideal method to include the data into the probabilistic model. It ensures a consistent probabilistic treatment of uncertainty, which is central in the prediction of rare events, where extrapolation from the domain of observation is common. We present a framework for performing Bayesian updating of rare event probabilities, termed BUS. It is based on a reinterpretation of the classical rejection-sampling approach to Bayesian analysis, which enables the use of established methods for estimating probabilities of rare events. By drawing upon these methods, the framework makes use of their computational efficiency. These methods include the First-Order Reliability Method (FORM), tailored importance sampling (IS) methods and Subset Simulation (SuS). In this contribution, we briefly review these methods in the context of the BUS framework and investigate their applicability to Bayesian analysis of rare events in different settings. We find that, for some applications, FORM can be highly efficient and is surprisingly accurate, enabling Bayesian analysis of rare events with just a few model evaluations. In a general setting, BUS implemented through IS and SuS is more robust and flexible.

  15. Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI.

    PubMed

    Prasad, Kedar N; Bondy, Stephen C

    2015-03-01

    Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain. PMID:25553619

  16. Episodes, events, and models.

    PubMed

    Khemlani, Sangeet S; Harrison, Anthony M; Trafton, J Gregory

    2015-01-01

    We describe a novel computational theory of how individuals segment perceptual information into representations of events. The theory is inspired by recent findings in the cognitive science and cognitive neuroscience of event segmentation. In line with recent theories, it holds that online event segmentation is automatic, and that event segmentation yields mental simulations of events. But it posits two novel principles as well: first, discrete episodic markers track perceptual and conceptual changes, and can be retrieved to construct event models. Second, the process of retrieving and reconstructing those episodic markers is constrained and prioritized. We describe a computational implementation of the theory, as well as a robotic extension of the theory that demonstrates the processes of online event segmentation and event model construction. The theory is the first unified computational account of event segmentation and temporal inference. We conclude by demonstrating now neuroimaging data can constrain and inspire the construction of process-level theories of human reasoning. PMID:26578934

  17. Episodes, events, and models

    PubMed Central

    Khemlani, Sangeet S.; Harrison, Anthony M.; Trafton, J. Gregory

    2015-01-01

    We describe a novel computational theory of how individuals segment perceptual information into representations of events. The theory is inspired by recent findings in the cognitive science and cognitive neuroscience of event segmentation. In line with recent theories, it holds that online event segmentation is automatic, and that event segmentation yields mental simulations of events. But it posits two novel principles as well: first, discrete episodic markers track perceptual and conceptual changes, and can be retrieved to construct event models. Second, the process of retrieving and reconstructing those episodic markers is constrained and prioritized. We describe a computational implementation of the theory, as well as a robotic extension of the theory that demonstrates the processes of online event segmentation and event model construction. The theory is the first unified computational account of event segmentation and temporal inference. We conclude by demonstrating now neuroimaging data can constrain and inspire the construction of process-level theories of human reasoning. PMID:26578934

  18. Divalent metals stabilize cellular prion proteins and alter the rate of proteinase-K dependent limited proteolysis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: The key biochemical event in the pathogenesis of prion diseases is the conversion of normal cellular prion proteins (PrP**c) to the proteinase K (PK) resistant, abnormal form (PrP**sc); however, the cellular mechanisms underlying the conversion remain enigmatic. Binding of divalent ca...

  19. MANGANESE UPREGULATES CELLULAR PRION PROTEINS AND INHIBITS THE RATE OF PROTEINASE-K DEPENDENT LIMITED PROTEOLYSIS IN NEURONAL CELLS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The key event in the pathogenesis of prion diseases is the conversion of normal cellular prion proteins (PrP**c) to the proteinase K (PK) resistant, abnormal form (PrP**sc); however, the cellular mechanisms underlying the conversion remain enigmatic. Binding of divalent cations such as copper to th...

  20. Multiscale Modeling of Cardiac Cellular Energetics

    PubMed Central

    BASSINGTHWAIGHTE, JAMES B.; CHIZECK, HOWARD J.; ATLAS, LES E.; QIAN, HONG

    2010-01-01

    Multiscale modeling is essential to integrating knowledge of human physiology starting from genomics, molecular biology, and the environment through the levels of cells, tissues, and organs all the way to integrated systems behavior. The lowest levels concern biophysical and biochemical events. The higher levels of organization in tissues, organs, and organism are complex, representing the dynamically varying behavior of billions of cells interacting together. Models integrating cellular events into tissue and organ behavior are forced to resort to simplifications to minimize computational complexity, thus reducing the model’s ability to respond correctly to dynamic changes in external conditions. Adjustments at protein and gene regulatory levels shortchange the simplified higher-level representations. Our cell primitive is composed of a set of subcellular modules, each defining an intracellular function (action potential, tricarboxylic acid cycle, oxidative phosphorylation, glycolysis, calcium cycling, contraction, etc.), composing what we call the “eternal cell,” which assumes that there is neither proteolysis nor protein synthesis. Within the modules are elements describing each particular component (i.e., enzymatic reactions of assorted types, transporters, ionic channels, binding sites, etc.). Cell subregions are stirred tanks, linked by diffusional or transporter-mediated exchange. The modeling uses ordinary differential equations rather than stochastic or partial differential equations. This basic model is regarded as a primitive upon which to build models encompassing gene regulation, signaling, and long-term adaptations in structure and function. During simulation, simpler forms of the model are used, when possible, to reduce computation. However, when this results in error, the more complex and detailed modules and elements need to be employed to improve model realism. The processes of error recognition and of mapping between different levels of

  1. The global event system

    SciTech Connect

    Winans, J.

    1994-03-02

    The support for the global event system has been designed to allow an application developer to control the APS event generator and receiver boards. This is done by the use of four new record types. These records are customized and are only supported by the device support modules for the APS event generator and receiver boards. The use of the global event system and its associated records should not be confused with the vanilla EPICS events and the associated event records. They are very different.

  2. Neurodata Without Borders: Creating a Common Data Format for Neurophysiology.

    PubMed

    Teeters, Jeffery L; Godfrey, Keith; Young, Rob; Dang, Chinh; Friedsam, Claudia; Wark, Barry; Asari, Hiroki; Peron, Simon; Li, Nuo; Peyrache, Adrien; Denisov, Gennady; Siegle, Joshua H; Olsen, Shawn R; Martin, Christopher; Chun, Miyoung; Tripathy, Shreejoy; Blanche, Timothy J; Harris, Kenneth; Buzsáki, György; Koch, Christof; Meister, Markus; Svoboda, Karel; Sommer, Friedrich T

    2015-11-18

    The Neurodata Without Borders (NWB) initiative promotes data standardization in neuroscience to increase research reproducibility and opportunities. In the first NWB pilot project, neurophysiologists and software developers produced a common data format for recordings and metadata of cellular electrophysiology and optical imaging experiments. The format specification, application programming interfaces, and sample datasets have been released. PMID:26590340

  3. Fluorescent sensing of fluoride in cellular system.

    PubMed

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F(-) detection in the past decades. Traditional methods for the detection of F(-) including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F(-) are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F(-), mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be

  4. Fluorescent Sensing of Fluoride in Cellular System

    PubMed Central

    Jiao, Yang; Zhu, Baocun; Chen, Jihua; Duan, Xiaohong

    2015-01-01

    Fluoride ions have the important roles in a lot of physiological activities related with biological and medical system, such as water fluoridation, caries treatment, and bone disease treatment. Great efforts have been made to develop new methods and strategies for F- detection in the past decades. Traditional methods for the detection of F- including ion chromatography, ion-selective electrodes, and spectroscopic techniques have the limitations in the biomedicine research. The fluorescent probes for F- are very promising that overcome some drawbacks of traditional fluoride detection methods. These probes exhibit high selectivity, high sensitivity as well as quick response to the detection of fluoride anions. The review commences with a brief description of photophysical mechanisms for fluorescent probes for fluoride, including photo induced electron transfer (PET), intramolecular charge transfer (ICT), fluorescence resonance energy transfer (FRET), and excited-state intramolecular proton transfer (ESIPT). Followed by a discussion about common dyes for fluorescent fluoride probes, such as anthracene, naphalimide, pyrene, BODIPY, fluorescein, rhodamine, resorufin, coumarin, cyanine, and near-infrared (NIR) dyes. We divide the fluorescent probes for fluoride in cellular application systems into nine groups, for example, type of hydrogen bonds, type of cleavage of Si-O bonds, type of Si-O bond cleavage and cylization reactions, etc. We also review the recent reported carriers in the delivery of fluorescent fluoride probes. Seventy-four typical fluorescent fluoride probes are listed and compared in detail, including quantum yield, reaction medium, excitation and emission wavelengths, linear detection range, selectivity for F-, mechanism, and analytical applications. Finally, we discuss the future challenges of the application of fluorescent fluoride probes in cellular system and in vivo. We wish that more and more excellent fluorescent fluoride probes will be developed

  5. Molecular and cellular constraints on proteins

    NASA Astrophysics Data System (ADS)

    Kortemme, Tanja

    Engineering proteins with new sequences, structures and functions has many exciting practical applications, and provides new ways to dissect design principles for function. Recent successes in computational protein design provide a cause for optimism. Yet many functions are currently too complex to engineer predictively, and successful design of new biological activities also requires an understanding of the functional pressures acting on proteins in the context of cells and organisms. I will present two vignettes describing our progress with dissecting both molecular and cellular constraints on protein function. In the first, we characterized the cost and benefit of protein production upon sequence perturbations in a classic system for gene regulation, the lac operon. Our results were unexpected in light of the common assumption that the dominant fitness costs are due to protein expression. Instead, we discovered a direct linear relationship between cost and lacpermease activity, not protein or mRNA production. The magnitude of the cost of permease activity, relative to protein production, has consequences for regulation. Our model predicts an advantage of direct regulation of protein activity (not just expression), providing a new explanation for the long-known mechanism of ``inducer exclusion'' that inhibits transport through the permease. Similar pressures and cost/benefit tradeoffs may be key to engineering synthetic systems with improved fitness. In the second vignette, I will describe our recent efforts to develop computational approaches that predict protein sequences consistent with multiple functional conformations. We expect such ``multi-constraint'' models to improve predictions of functional sequences determined by deep mutational scanning in bacteria, to provide insights into how the balance between functional conformations shapes sequence space, and to highlight molecular and cellular constraints that cannot be captured by the model.

  6. Hydrogen Peroxide Probes Directed to Different Cellular Compartments

    PubMed Central

    Malinouski, Mikalai; Zhou, You; Belousov, Vsevolod V.; Hatfield, Dolph L.; Gladyshev, Vadim N.

    2011-01-01

    Background Controlled generation and removal of hydrogen peroxide play important roles in cellular redox homeostasis and signaling. We used a hydrogen peroxide biosensor HyPer, targeted to different compartments, to examine these processes in mammalian cells. Principal Findings Reversible responses were observed to various redox perturbations and signaling events. HyPer expressed in HEK 293 cells was found to sense low micromolar levels of hydrogen peroxide. When targeted to various cellular compartments, HyPer occurred in the reduced state in the nucleus, cytosol, peroxisomes, mitochondrial intermembrane space and mitochondrial matrix, but low levels of the oxidized form of the biosensor were also observed in each of these compartments, consistent with a low peroxide tone in mammalian cells. In contrast, HyPer was mostly oxidized in the endoplasmic reticulum. Using this system, we characterized control of hydrogen peroxide in various cell systems, such as cells deficient in thioredoxin reductase, sulfhydryl oxidases or subjected to selenium deficiency. Generation of hydrogen peroxide could also be monitored in various compartments following signaling events. Conclusions We found that HyPer can be used as a valuable tool to monitor hydrogen peroxide generated in different cellular compartments. The data also show that hydrogen peroxide generated in one compartment could translocate to other compartments. Our data provide information on compartmentalization, dynamics and homeostatic control of hydrogen peroxide in mammalian cells. PMID:21283738

  7. Cellular immune responses to HIV

    NASA Astrophysics Data System (ADS)

    McMichael, Andrew J.; Rowland-Jones, Sarah L.

    2001-04-01

    The cellular immune response to the human immunodeficiency virus, mediated by T lymphocytes, seems strong but fails to control the infection completely. In most virus infections, T cells either eliminate the virus or suppress it indefinitely as a harmless, persisting infection. But the human immunodeficiency virus undermines this control by infecting key immune cells, thereby impairing the response of both the infected CD4+ T cells and the uninfected CD8+ T cells. The failure of the latter to function efficiently facilitates the escape of virus from immune control and the collapse of the whole immune system.

  8. Quantum cellular automata without particles

    NASA Astrophysics Data System (ADS)

    Meyer, David A.; Shakeel, Asif

    2016-01-01

    Quantum cellular automata (QCA) constitute space and time homogeneous discrete models for quantum field theories (QFTs). Although QFTs are defined without reference to particles, computations are done in terms of Feynman diagrams, which are explicitly interpreted in terms of interacting particles. Similarly, the easiest QCA to construct are quantum lattice gas automata (QLGA). A natural question then is, which QCA are not QLGA? Here we construct a nontrivial example of such a QCA; it provides a simple model in 1 +1 dimensions with no particle interpretation at the scale where the QCA dynamics are homogeneous.

  9. Universal map for cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2012-08-01

    A universal map is derived for all deterministic 1D cellular automata (CAs) containing no freely adjustable parameters and valid for any alphabet size and any neighborhood range (including non-symmetrical neighborhoods). The map can be extended to an arbitrary number of dimensions and topologies and to arbitrary order in time. Specific CA maps for the famous Conway's Game of Life and Wolfram's 256 elementary CAs are given. An induction method for CAs, based in the universal map, allows mathematical expressions for the orbits of a wide variety of elementary CAs to be systematically derived.

  10. Therapeutic cloning and cellular reprogramming.

    PubMed

    Rodriguez, Ramon M; Ross, Pablo J; Cibelli, Jose B

    2012-01-01

    Embryonic stem cells are capable of differentiating into any cell-type present in an adult organism, and constitute a renewable source of tissue for regenerative therapies. The transplant of allogenic stem cells is challenging due to the risk of immune rejection. Nevertheless, somatic cell reprogramming techniques allow the generation of isogenic embryonic stem cells, genetically identical to the patient. In this chapter we will discuss the cellular reprogramming techniques in the context of regenerative therapy and the biological and technical barriers that they will need to overcome before clinical use. PMID:22457116

  11. Symmetry analysis of cellular automata

    NASA Astrophysics Data System (ADS)

    García-Morales, V.

    2013-01-01

    By means of B-calculus [V. García-Morales, Phys. Lett. A 376 (2012) 2645] a universal map for deterministic cellular automata (CAs) has been derived. The latter is shown here to be invariant upon certain transformations (global complementation, reflection and shift). When constructing CA rules in terms of rules of lower range a new symmetry, “invariance under construction” is uncovered. Modular arithmetic is also reformulated within B-calculus and a new symmetry of certain totalistic CA rules, which calculate the Pascal simplices modulo an integer number p, is then also uncovered.

  12. Primitive control of cellular metabolism

    NASA Technical Reports Server (NTRS)

    Mitz, M. A.

    1974-01-01

    It is pointed out that control substances must have existed from the earliest times in the evolution of life and that the same control mechanisms must exist today. The investigation reported is concerned with the concept that carbon dioxide is a primitive regulator of cell function. The effects of carbon dioxide on cellular materials are examined, taking into account questions of solubilization, dissociation, changes of charge, stabilization, structural changes, wettability, the exclusion of other gases, the activation of compounds, changes in plasticity, and changes in membrane permeability.

  13. The Cellular Basis of Aging

    PubMed Central

    Scoggin, Charles H.

    1981-01-01

    Normal cells have only a finite life span before they die. The process known as aging may occur as a result of continued damage to the cell or as a result of expression of predetermined information within the genetic structure of the cell. Both processes lead to progressive cellular dysfunction which is evidenced by the organs of the body as aging. By understanding how individual cells age we will gain insight into how the body as a whole ages. The impact of such knowledge on science and society is a matter of both conjecture and concern. PMID:7336718

  14. Herpes simplex virus type 1 colitis in a patient with common variable immunodeficiency syndrome.

    PubMed

    Dray, Xavier; Treton, Xavier; Mazeron, Marie-Christine; Lavergne-Slove, Anne; Joly, Francisca; Mimram, Dora; Attar, Alain; Tobelem, Gérard; Bouhnik, Yoram

    2006-05-01

    We report on a case of herpes simplex virus (HSV) type 1 colitis in a 69-year-old patient with common variable immunodeficiency syndrome. A treatment with polyvalent immunoglobulins was discontinued in April 2001. In March 2004 she developed chronic diarrhoea related to rectosigmoidal and caecal ulcerations. In November 2004, HSV was recovered in tissue culture from colonic biopsies. Valaciclovir was then started, leading the patient to clinical remission at day 4, and continued for a 6-week course (without any secondary antiviral prophylaxis). Colonic biopsies were negative for HSV by tissue culture and PCR within 3 weeks of antiviral treatment. Intravenous polyvalent immunoglobulin infusions were readministered within the third week of antiviral treatment. She has declared no clinical event since this period. Three months after the antiviral treatment was achieved, a rectosigmoidoscopy showed an ad-integrum macroscopic and histological mucosal healing whereas PCR was negative for HSV in the colonic tissue. As a large proportion of patients with common variable immunodeficiency syndrome present not only as a humoral immunodeficiency but also as a defect in the cellular immunity compartment (with T-cell deficits), HSV, as well as cytomegalovirus, should be investigated in patients with common variable immunodeficiency syndrome presenting colitis. PMID:16607152

  15. Protein accounting in the cellular economy

    PubMed Central

    Vázquez-Laslop, Nora; Mankin, Alexander S.

    2014-01-01

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. (2014) gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the needs. PMID:24766801

  16. Protein accounting in the cellular economy.

    PubMed

    Vázquez-Laslop, Nora; Mankin, Alexander S

    2014-04-24

    Knowing the copy number of cellular proteins is critical for understanding cell physiology. By being able to measure the absolute synthesis rates of the majority of cellular proteins, Li et al. gain insights into key aspects of translation regulation and fundamental principles of cellular strategies to adjust protein synthesis according to the functional needs. PMID:24766801

  17. Actions of ultraviolet light on cellular structures.

    PubMed

    Pattison, David I; Davies, Michael J

    2006-01-01

    Solar radiation is the primary source of human exposure to ultraviolet (UV) radiation. Overexposure without suitable protection (i.e., sunscreen and clothing) has been implicated in mutagenesis and the onset of skin cancer. These effects are believed to be initiated by UV-mediated cellular damage, with proteins and DNA as primary targets due to a combination of their UV absorption characteristics and their abundance in cells. UV radiation can mediate damage via two different mechanisms: (a) direct absorption of the incident light by the cellular components, resulting in excited state formation and subsequent chemical reaction, and (b) photosensitization mechanisms, where the light is absorbed by endogenous (or exogenous) sensitizers that are excited to their triplet states. The excited photosensitizers can induce cellular damage by two mechanisms: (a) electron transfer and hydrogen abstraction processes to yield free radicals (Type I); or (b) energy transfer with O2 to yield the reactive excited state, singlet oxygen (Type II). Direct UV absorption by DNA leads to dimers of nucleic acid bases including cyclobutane pyrimidine species and pyrimidine (6-4) pyrimidone compounds, together with their Dewar isomers. These three classes of dimers are implicated in the mutagenicity of UV radiation, which is typified by a high level of CC-->TT and C-->T transversions. Single base modifications can also occur via sensitized reactions including Type 1 and Type II processes. The main DNA product generated by (1)O2 is 8-oxo-Gua; this is a common lesion in DNA and is formed by a range of other oxidants in addition to UV. The majority of UV-induced protein damage appears to be mediated by (1)O2, which reacts preferentially with Trp, His, Tyr, Met, Cys and cystine side chains. Direct photo-oxidation reactions (particularly with short-wavelength UV) and radicals can also be formed via triplet excited states of some of these side chains. The initial products of (1)O2-mediated

  18. Mathematics, thermodynamics, and modeling to address ten common misconceptions about protein structure, folding, and stability.

    PubMed

    Robic, Srebrenka

    2010-01-01

    To fully understand the roles proteins play in cellular processes, students need to grasp complex ideas about protein structure, folding, and stability. Our current understanding of these topics is based on mathematical models and experimental data. However, protein structure, folding, and stability are often introduced as descriptive, qualitative phenomena in undergraduate classes. In the process of learning about these topics, students often form incorrect ideas. For example, by learning about protein folding in the context of protein synthesis, students may come to an incorrect conclusion that once synthesized on the ribosome, a protein spends its entire cellular life time in its fully folded native confirmation. This is clearly not true; proteins are dynamic structures that undergo both local fluctuations and global unfolding events. To prevent and address such misconceptions, basic concepts of protein science can be introduced in the context of simple mathematical models and hands-on explorations of publicly available data sets. Ten common misconceptions about proteins are presented, along with suggestions for using equations, models, sequence, structure, and thermodynamic data to help students gain a deeper understanding of basic concepts relating to protein structure, folding, and stability. PMID:20810950

  19. Inflight Medical Events in the Shuttle Program

    NASA Technical Reports Server (NTRS)

    Baisden, Denise L.; Effenhauser, R. K.; Wear, Mary L.

    1999-01-01

    Since the first launch of the Space Shuttle in 1981, the astronauts and their flight surgeons have dealt with a variety of inflight medical issues. A review will be provided of these issues as well as medications used in the treatment of these medical problems. Detailed medical debriefs are conducted by the flight ,surgeon with the individual crewmembers three days after landing. These debriefs were review for Shuttle flights from 1988 through 1999 to determine the frequency of inflight medical events. Medical events were grouped by ICD category and the frequency of medical events within those categories were reviewed. The ICD category of Symptoms, Signs and Ill-defined Conditions had the most medical events. Facial fullness and headache were the most common complaints within this category. The ICD category of Respiratory System had the next most common medical events with sinus congestion being the most common complaint. This was followed by Digestive System complaints and Nervous System/Sense Organ complaints. A variety of inflight medical events have occurred throughout the Shuttle program. Fortunately, the majority of these problems have been minor and have been well within the capability of the medical equipment flown and the skills of the Crew Medical Officers. Medical ,problems/procedures that are routine on the ground often present unique problems in the space flight environment. It is important that the flight surgeon understand the common medical problems encountered.

  20. Oxidative Stress and Ca2+ Release Events in Mouse Cardiomyocytes

    PubMed Central

    Shirokova, Natalia; Kang, Chifei; Fernandez-Tenorio, Miguel; Wang, Wei; Wang, Qiongling; Wehrens, Xander H.T.; Niggli, Ernst

    2014-01-01

    Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca2+ signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca2+ release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxidation of RyR2s was found to increase the open probability of the channel, whereas CaMKII can be activated independent of Ca2+ through oxidation. Here, we investigated how oxidative stress affects RyR2 function and SR Ca2+ signaling in situ, by analyzing Ca2+ sparks in permeabilized mouse cardiomyocytes under a broad range of oxidative conditions. The results show that with increasing oxidative stress Ca2+ spark duration is prolonged. In addition, long and very long-lasting (up to hundreds of milliseconds) localized Ca2+ release events started to appear, eventually leading to sarcoplasmic reticulum (SR) Ca2+ depletion. These changes of release duration could be prevented by the CaMKII inhibitor KN93 and did not occur in mice lacking the CaMKII-specific S2814 phosphorylation site on RyR2. The appearance of long-lasting Ca2+ release events was paralleled by an increase of RyR2 oxidation, but also by RyR-S2814 phosphorylation, and by CaMKII oxidation. Our results suggest that in a strongly oxidative environment oxidation-dependent activation of CaMKII leads to RyR2 phosphorylation and thereby contributes to the massive prolongation of SR Ca2+ release events. PMID:25517148

  1. Work and common psychiatric disorders.

    PubMed

    Henderson, M; Harvey, S B; Overland, S; Mykletun, A; Hotopf, M

    2011-05-01

    Psychiatric disorders are now the most common reason for long-term sickness absence. The associated loss in productivity and the payment of disability benefits places a substantial burden on the economies of many developed countries. The occupational dysfunction associated with psychiatric disorders can also lead to poverty and social isolation. As a result the area of work and psychiatric disorders is a high priority for policymakers. There are two main agendas: for many researchers and clinicians the focus is on the need to overcome stigma and ensure people with severe psychiatric disorders have meaningful work; however the public health agenda predominantly relates to the more common disorders such as depression and anxiety, which contribute a greater burden of disability benefits and pensions. In this review we attempt to address this second agenda. The relatively sparse evidence available reveals a complex field with significant interplay between medical, psychological social and cultural factors. Sick leave can be a 'process' as well as an 'event'. In this review we propose a staged model where different risk and protective factors contribute to the onset of psychiatric disorders in the working population, the onset of short-term sickness absence, and the transition from short- to long-term absence. We also examine strategies to manage psychiatric disorder in the workforce with a view towards returning the employee to work. Our aim in this review is to highlight the complexity of the area, to stimulate debate and to identify important gaps in knowledge where further research might benefit both patients and wider society. PMID:21558098

  2. Developing an effective 2-D urban flood inundation model for city emergency management based on cellular automata

    NASA Astrophysics Data System (ADS)

    Liu, L.; Liu, Y.; Wang, X.; Yu, D.; Liu, K.; Huang, H.; Hu, G.

    2015-03-01

    Flash floods have occurred frequently in the urban areas of southern China. An effective process-oriented urban flood inundation model is urgently needed for urban storm-water and emergency management. This study develops an efficient and flexible cellular automaton (CA) model to simulate storm-water runoff and the flood inundation process during extreme storm events. The process of infiltration, inlets discharge and flow dynamics can be simulated with little preprocessing on commonly available basic urban geographic data. In this model, a set of gravitational diverging rules are implemented to govern the water flow in a rectangular template of three cells by three cells of a raster layer. The model is calibrated by one storm event and validated by another in a small urban catchment in Guangzhou of southern China. The depth of accumulated water at the catchment outlet is interpreted from street-monitoring closed-circuit television (CCTV) videos and verified by on-site survey. A good level of agreement between the simulated process and the reality is reached for both storm events. The model reproduces the changing extent and depth of flooded areas at the catchment outlet with an accuracy of 4 cm in water depth. Comparisons with a physically based 2-D model (FloodMap) show that the model is capable of effectively simulating flow dynamics. The high computational efficiency of the CA model can meet the needs of city emergency management.

  3. Chlorovirus Skp1-Binding Ankyrin Repeat Protein Interplay and Mimicry of Cellular Ubiquitin Ligase Machinery

    PubMed Central

    Noel, Eric A.; Kang, Ming; Adamec, Jiri; Oyler, George A.

    2014-01-01

    ABSTRACT The ubiquitin-proteasome system is targeted by many viruses that have evolved strategies to redirect host ubiquitination machinery. Members of the genus Chlorovirus are proposed to share an ancestral lineage with a broader group of related viruses, nucleo-cytoplasmic large DNA viruses (NCLDV). Chloroviruses encode an Skp1 homolog and ankyrin repeat (ANK) proteins. Several chlorovirus-encoded ANK repeats contain C-terminal domains characteristic of cellular F-boxes or related NCLDV chordopox PRANC (pox protein repeats of ankyrin at C-terminal) domains. These observations suggested that this unique combination of Skp1 and ANK repeat proteins might form complexes analogous to the cellular Skp1-Cul1-F-box (SCF) ubiquitin ligase complex. We identified two ANK proteins from the prototypic chlorovirus Paramecium bursaria chlorella virus-1 (PBCV-1) that functioned as binding partners for the virus-encoded Skp1, proteins A682L and A607R. These ANK proteins had a C-terminal Skp1 interactional motif that functioned similarly to cellular F-box domains. A C-terminal motif of ANK protein A682L binds Skp1 proteins from widely divergent species. Yeast two-hybrid analyses using serial domain deletion constructs confirmed the C-terminal localization of the Skp1 interactional motif in PBCV-1 A682L. ANK protein A607R represents an ANK family with one member present in all 41 sequenced chloroviruses. A comprehensive phylogenetic analysis of these related ANK and viral Skp1 proteins suggested partnered function tailored to the host alga or common ancestral heritage. Here, we show protein-protein interaction between corresponding family clusters of virus-encoded ANK and Skp1 proteins from three chlorovirus types. Collectively, our results indicate that chloroviruses have evolved complementing Skp1 and ANK proteins that mimic cellular SCF-associated proteins. IMPORTANCE Viruses have evolved ways to direct ubiquitination events in order to create environments conducive to their

  4. Common pediatric epilepsy syndromes.

    PubMed

    Park, Jun T; Shahid, Asim M; Jammoul, Adham

    2015-02-01

    Benign rolandic epilepsy (BRE), childhood idiopathic occipital epilepsy (CIOE), childhood absence epilepsy (CAE), and juvenile myoclonic epilepsy (JME) are some of the common epilepsy syndromes in the pediatric age group. Among the four, BRE is the most commonly encountered. BRE remits by age 16 years with many children requiring no treatment. Seizures in CAE also remit at the rate of approximately 80%; whereas, JME is considered a lifelong condition even with the use of antiepileptic drugs (AEDs). Neonates and infants may also present with seizures that are self-limited with no associated psychomotor disturbances. Benign familial neonatal convulsions caused by a channelopathy, and inherited in an autosomal dominant manner, have a favorable outcome with spontaneous resolution. Benign idiopathic neonatal seizures, also referred to as "fifth-day fits," are an example of another epilepsy syndrome in infants that carries a good prognosis. BRE, CIOE, benign familial neonatal convulsions, benign idiopathic neonatal seizures, and benign myoclonic epilepsy in infancy are characterized as "benign" idiopathic age-related epilepsies as they have favorable implications, no structural brain abnormality, are sensitive to AEDs, have a high remission rate, and have no associated psychomotor disturbances. However, sometimes selected patients may have associated comorbidities such as cognitive and language delay for which the term "benign" may not be appropriate. PMID:25658216

  5. Common Variable Immunodeficiency.

    PubMed

    Saikia, Biman; Gupta, Sudhir

    2016-04-01

    Common variable immunodeficiency (CVID) is the most common primary immunodeficiency of young adolescents and adults which also affects the children. The disease remains largely under-diagnosed in India and Southeast Asian countries. Although in majority of cases it is sporadic, disease may be inherited in a autosomal recessive pattern and rarely, in autosomal dominant pattern. Patients, in addition to frequent sino-pulmonary infections, are also susceptible to various autoimmune diseases and malignancy, predominantly lymphoma and leukemia. Other characteristic lesions include lymphocytic and granulomatous interstitial lung disease, and nodular lymphoid hyperplasia of gut. Diagnosis requires reduced levels of at least two immunoglobulin isotypes: IgG with IgA and/or IgM and impaired specific antibody response to vaccines. A number of gene mutations have been described in CVID; however, these genetic alterations account for less than 20% of cases of CVID. Flow cytometry aptly demonstrates a disturbed B cell homeostasis with reduced or absent memory B cells and increased CD21(low) B cells and transitional B cell populations. Approximately one-third of patients with CVID also display T cell functional defects. Immunoglobulin therapy remains the mainstay of treatment. Immunologists and other clinicians in India and other South East Asian countries need to be aware of CVID so that early diagnosis can be made, as currently, majority of these patients still go undiagnosed. PMID:26868026

  6. Commonly used gastrointestinal drugs.

    PubMed

    Aggarwal, Annu; Bhatt, Mohit

    2014-01-01

    This chapter reviews the spectrum and mechanisms of neurologic adverse effects of commonly used gastrointestinal drugs including antiemetics, promotility drugs, laxatives, antimotility drugs, and drugs for acid-related disorders. The commonly used gastrointestinal drugs as a group are considered safe and are widely used. A range of neurologic complications are reported following use of various gastrointestinal drugs. Acute neurotoxicities, including transient akathisias, oculogyric crisis, delirium, seizures, and strokes, can develop after use of certain gastrointestinal medications, while disabling and pervasive tardive syndromes are described following long-term and often unsupervised use of phenothiazines, metoclopramide, and other drugs. In rare instances, some of the antiemetics can precipitate life-threatening extrapyramidal reactions, neuroleptic malignant syndrome, or serotonin syndrome. In contrast, concerns about the cardiovascular toxicity of drugs such as cisapride and tegaserod have been grave enough to lead to their withdrawal from many world markets. Awareness and recognition of the neurotoxicity of gastrointestinal drugs is essential to help weigh the benefit of their use against possible adverse effects, even if uncommon. Furthermore, as far as possible, drugs such as metoclopramide and others that can lead to tardive dyskinesias should be used for as short time as possible, with close clinical monitoring and patient education. PMID:24365343

  7. Cellular Symmetry Breaking during Caenorhabditis elegans Development

    PubMed Central

    Munro, Edwin; Bowerman, Bruce

    2009-01-01

    The nematode worm Caenorhabditis elegans has produced a wellspring of insights into mechanisms that govern cellular symmetry breaking during animal development. Here we focus on two highly conserved systems that underlie many of the key symmetry-breaking events that occur during embryonic and larval development in the worm. One involves the interplay between Par proteins, Rho GTPases, and the actomyosin cytoskeleton and mediates asymmetric cell divisions that establish the germline. The other uses elements of the Wnt signaling pathway and a highly reiterative mechanism that distinguishes anterior from posterior daughter cell fates. Much of what we know about these systems comes from intensive study of a few key events—Par/Rho/actomyosin-mediated polarization of the zygote in response to a sperm-derived cue and the Wnt-mediated induction of endoderm at the four-cell stage. However, a growing body of work is revealing how C. elegans exploits elements/variants of these systems to accomplish a diversity of symmetry-breaking tasks throughout embryonic and larval development. PMID:20066102

  8. Cellular signaling in eclosion hormone action.

    PubMed

    Morton, David B.; Simpson, P Jeanette

    2002-01-01

    Eclosion hormone (EH) is a 62 amino acid neuropeptide that plays an integral role in triggering ecdysis behavior at the end of each molt. At least three populations of cells are thought to be targets for EH, each of which show an EH-stimulated increase in the intracellular messenger guanosine 3', 5' cyclic monophosphate (cGMP). These EH target cells are believed to include two pairs of neurons in each of the ganglia of the ventral nerve cord (VNC) that contain the neuropeptide crustacean cardioactive peptide (CCAP), the Inka cells of the peripheral epitracheal glands and intrinsic non-neuronal cells in the abdominal transverse nerves. This review describes likely signaling cascades that result in the EH-stimulated cGMP increase. Several lines of evidence suggest the involvement of a novel nitric oxide insensitive soluble guanylyl cyclase (GC). A novel GC with these properties has recently been identified and we also present evidence to suggest that it is activated by EH and describe possible pathways for its activation. In addition, we review our current knowledge on the cellular and molecular events that take place downstream of the increase in cGMP. PMID:12770127

  9. Cellular-enabled water quality measurements

    NASA Astrophysics Data System (ADS)

    Zhao, Y.; Kerkez, B.

    2013-12-01

    While the past decade has seen significant improvements in our ability to measure nutrients and other water quality parameters, the use of these sensors has yet to gain traction due to their costprohibitive nature and deployment expertise required on the part of researchers. Furthermore, an extra burden is incurred when real-time data access becomes an experimental requirement. We present an open-source hardware design to facilitate the real-time, low-cost, and robust measurements of water quality across large urbanized areas. Our hardware platform interfaces an embedded, vastly configurable, high-precision, ultra-low power measurement system, with a low-power cellular module. Each sensor station is configured with an IP address, permitting reliable streaming of sensor data to off-site locations as measurements are made. We discuss the role of high-quality hardware components during extreme event scenarios, and present preliminary performance metrics that validate the ability of the platform to provide streaming access to sensor measurements.

  10. Ground-roll attenuation using modified common-offset-common-reflection-surface stacking

    NASA Astrophysics Data System (ADS)

    Rastegar, Seyyed Ali Fa'al; Javaherian, Abdolrahim; Farajkhah, Naser Keshavarz; Monfared, Mehrdad Soleimani; Zarei, Abbas

    2016-06-01

    We modified the common-offset-common-reflection-surface (COCRS) method to attenuate ground roll, the coherent noise typically generated by a low-velocity, low-frequency, and high-amplitude Rayleigh wave. The COCRS operator is based on hyperbolas, thus it fits events with hyperbolic traveltimes such as reflection events in prestack data. Conversely, ground roll is linear in the common-midpoint (CMP) and common-shot gathers and can be distinguished and attenuated by the COCRS operator. Thus, we search for the dip and curvature of the reflections in the common-shot gathers prior to the common-offset section. Because it is desirable to minimize the damage to the reflection amplitudes, we only stack the multicoverage data in the ground-roll areas. Searching the CS gathers before the CO section is another modification of the conventional COCRS stacking. We tested the proposed method using synthetic and real data sets from western Iran. The results of the ground-roll attenuation with the proposed method were compared with results of the f-k filtering and conventional COCRS stacking after f-k filtering. The results show that the proposed method attenuates the aliased and nonaliased ground roll better than the f-k filtering and conventional CRS stacking. However, the computation time was higher than other common methods such as f-k filtering.

  11. Cellular senescence and protein degradation

    PubMed Central

    Deschênes-Simard, Xavier; Lessard, Frédéric; Gaumont-Leclerc, Marie-France; Bardeesy, Nabeel; Ferbeyre, Gerardo

    2014-01-01

    Autophagy and the ubiquitin–proteasome pathway (UPP) are the major protein degradation systems in eukaryotic cells. Whereas the former mediate a bulk nonspecific degradation, the UPP allows a rapid degradation of specific proteins. Both systems have been shown to play a role in tumorigenesis, and the interest in developing therapeutic agents inhibiting protein degradation is steadily growing. However, emerging data point to a critical role for autophagy in cellular senescence, an established tumor suppressor mechanism. Recently, a selective protein degradation process mediated by the UPP was also shown to contribute to the senescence phenotype. This process is tightly regulated by E3 ubiquitin ligases, deubiquitinases, and several post-translational modifications of target proteins. Illustrating the complexity of UPP, more than 600 human genes have been shown to encode E3 ubiquitin ligases, a number which exceeds that of the protein kinases. Nevertheless, our knowledge of proteasome-dependent protein degradation as a regulated process in cellular contexts such as cancer and senescence remains very limited. Here we discuss the implications of protein degradation in senescence and attempt to relate this function to the protein degradation pattern observed in cancer cells. PMID:24866342

  12. Micromechanics of cellularized biopolymer networks

    PubMed Central

    Jones, Christopher A. R.; Cibula, Matthew; Feng, Jingchen; Krnacik, Emma A.; McIntyre, David H.; Levine, Herbert; Sun, Bo

    2015-01-01

    Collagen gels are widely used in experiments on cell mechanics because they mimic the extracellular matrix in physiological conditions. Collagen gels are often characterized by their bulk rheology; however, variations in the collagen fiber microstructure and cell adhesion forces cause the mechanical properties to be inhomogeneous at the cellular scale. We study the mechanics of type I collagen on the scale of tens to hundreds of microns by using holographic optical tweezers to apply pN forces to microparticles embedded in the collagen fiber network. We find that in response to optical forces, particle displacements are inhomogeneous, anisotropic, and asymmetric. Gels prepared at 21 °C and 37 °C show qualitative difference in their micromechanical characteristics. We also demonstrate that contracting cells remodel the micromechanics of their surrounding extracellular matrix in a strain- and distance-dependent manner. To further understand the micromechanics of cellularized extracellular matrix, we have constructed a computational model which reproduces the main experiment findings. PMID:26324923

  13. Cellular uptake of metallated cobalamins.

    PubMed

    Tran, Mai Thanh Quynh; Stürup, Stefan; Lambert, Ian Henry; Gammelgaard, Bente; Furger, Evelyne; Alberto, Roger

    2016-03-16

    Cellular uptake of vitamin B12-cisplatin conjugates was estimated via detection of their metal constituents (Co, Pt, and Re) by inductively coupled plasma mass spectrometry (ICP-MS). Vitamin B12 (cyano-cob(iii)alamin) and aquo-cob(iii)alamin [Cbl-OH2](+), which differ in the β-axial ligands (CN(-) and H2O, respectively), were included as control samples. The results indicated that B12 derivatives delivered cisplatin to both cellular cytosol and nuclei with an efficiency of one third compared to the uptake of free cisplatin cis-[Pt(II)Cl2(NH3)2]. In addition, uptake of charged B12 derivatives including [Cbl-OH2](+), [{Co}-CN-{cis-PtCl(NH3)2}](+), [{Re}-{Co}-CN-{cis-PtCl(NH3)2}](+), and [{Co}-CN-{trans-Pt(Cyt)(NH3)2}](2+) (Cyt = cytarabin) was high compared to neutral B12, which implied the existence of an additional internalization pathway for charged B12 vitamin analogs. The affinities of the charged B12 derivatives to the B12 transporters HC, IF and TC were similar to that of native vitamin B12. PMID:26739575

  14. Cellular Therapy for Heart Failure.

    PubMed

    Psaltis, Peter J; Schwarz, Nisha; Toledo-Flores, Deborah; Nicholls, Stephen J

    2016-01-01

    The pathogenesis of cardiomyopathy and heart failure (HF) is underpinned by complex changes at subcellular, cellular and extracellular levels in the ventricular myocardium. For all of the gains that conventional treatments for HF have brought to mortality and morbidity, they do not adequately address the loss of cardiomyocyte numbers in the remodeling ventricle. Originally conceived to address this problem, cellular transplantation for HF has already gone through several stages of evolution over the past two decades. Various cell types and delivery routes have been implemented to positive effect in preclinical models of ischemic and nonischemic cardiomyopathy, with pleiotropic benefits observed in terms of myocardial remodeling, systolic and diastolic performance, perfusion, fibrosis, inflammation, metabolism and electrophysiology. To a large extent, these salubrious effects are now attributed to the indirect, paracrine capacity of transplanted stem cells to facilitate endogenous cardiac repair processes. Promising results have also followed in early phase human studies, although these have been relatively modest and somewhat inconsistent. This review details the preclinical and clinical evidence currently available regarding the use of pluripotent stem cells and adult-derived progenitor cells for cardiomyopathy and HF. It outlines the important lessons that have been learned to this point in time, and balances the promise of this exciting field against the key challenges and questions that still need to be addressed at all levels of research, to ensure that cell therapy realizes its full potential by adding to the armamentarium of HF management. PMID:27280304

  15. CELLULAR PATHOGENESIS OF DIABETIC GASTROENTEROPATHY

    PubMed Central

    Ördög, Tamás; Hayashi, Yujiro; Gibbons, Simon J.

    2010-01-01

    SUMMARY Gastroenteropathy manifesting in upper gastrointestinal symptoms, delayed gastric emptying, constipation, diarrhea and fecal incontinence occurs frequently in patients with diabetes mellitus and represents a significant health care burden. Current treatments are largely symptomatic and ineffective. Better understanding of the cellular and molecular pathogenesis of these disorders is required for the development of more effective therapies. Recent advances in our understanding of the inherent, high-level complexities of the control systems that execute and regulate gastrointestinal motility, together with the utilization of new experimental models and sophisticated physiological, morphological and molecular techniques have lead to the realization that diabetic gastroenteropathies cannot be ascribed to any singular defect or dysfunction. In fact, these disorders are multifactorial and involve a spectrum of metabolic and dystrophic changes that can potentially affect all key components of motor control including the systemic autonomic and enteric nervous systems, interstitial cells of Cajal and smooth muscle cells. Candidate pathomechanisms are also varied and include imbalance between pro- and anti-oxidative factors, altered trophic stimuli to mature cells and their progenitors, and, possibly, autoimmune factors. The goal of this paper is to review the cellular changes underlying diabetic gastroenteropathies and their potential causes, with particular focus on functional interactions between various cell types. It is proposed that diabetic gastroenteropathies should be considered a form of gastrointestinal neuromuscular dystrophy rather than a “functional” disorder. Future research should identify ways to block cytotoxic factors, support the regeneration of damaged cells and translate the experimental findings into new treatment modalities. PMID:19829287

  16. Cellular Biology of Prion Diseases

    PubMed Central

    Harris, David A.

    1999-01-01

    Prion diseases are fatal neurodegenerative disorders of humans and animals that are important because of their impact on public health and because they exemplify a novel mechanism of infectivity and biological information transfer. These diseases are caused by conformational conversion of a normal host glycoprotein (PrPC) into an infectious isoform (PrPSc) that is devoid of nucleic acid. This review focuses on the current understanding of prion diseases at the cell biological level. The characteristics of the diseases are introduced, and a brief history and description of the prion hypothesis are given. Information is then presented about the structure, expression, biosynthesis, and possible function of PrPC, as well as its posttranslational processing, cellular localization, and trafficking. The latest findings concerning PrPSc are then discussed, including cell culture systems used to generate this pathogenic isoform, the subcellular distribution of the protein, its membrane attachment, proteolytic processing, and its kinetics and sites of synthesis. Information is also provided on molecular models of the PrPC→PrPSc conversion reaction and the possible role of cellular chaperones. The review concludes with suggestions of several important avenues for future investigation. PMID:10398674

  17. Vaccine Adverse Events

    MedlinePlus

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  18. New PHOBOS results on event-by-event fluctuations

    NASA Astrophysics Data System (ADS)

    Alver, B.; Back, B. B.; Baker, M. D.; Ballintijn, M.; Barton, D. S.; Betts, R. R.; Bickley, A. A.; Bindel, R.; Budzanowski, A.; Busza, W.; Carroll, A.; Chai, Z.; Chetluru, V.; Decowski, M. P.; García, E.; Gburek, T.; George, N.; Gulbrandsen, K.; Gushue, S.; Halliwell, C.; Hamblen, J.; Heintzelman, G. A.; Henderson, C.; Harnarine, I.; Hofman, D. J.; Hollis, R. S.; Hołyński, R.; Holzman, B.; Iordanova, A.; Johnson, E.; Kane, J. L.; Khan, N.; Kucewicz, W.; Kulinich, P.; Kuo, C. M.; Li, W.; Lin, W. T.; Loizides, C.; Manly, S.; Mignerey, A. C.; Nouicer, R.; Olszewski, A.; Pak, R.; Park, I. C.; Reed, C.; Remsberg, L. P.; Reuter, M.; Richardson, E.; Roland, C.; Roland, G.; Rosenberg, L.; Sagerer, J.; Sarin, P.; Sawicki, P.; Sedykh, I.; Skulski, W.; Smith, C. E.; Stankiewicz, M. A.; Steinberg, P.; Stephans, G. S. F.; Sukhanov, A.; Szostak, A.; Tang, J.-L.; Tonjes, M. B.; Trzupek, A.; Vale, C.; van Nieuwenhuizen, G. J.; Vaurynovich, S. S.; Verdier, R.; Veres, G. I.; Walters, P.; Wenger, E.; Willhelm, D.; Wolfs, F. L. H.; Wosiek, B.; Woźniak, K.; Wuosmaa, A. H.; Wyngaardt, S.; Wysłouch, B.

    2006-04-01

    We present new results from the PHOBOS experiment at RHIC on event-by-event fluctuations of particle multiplicities and angular distributions in nucleus-nucleus collisions at RHIC. Our data for Au+Au collisions at √sNN = 200 GeV show that at a level of 10-4 or less, no rare, large-amplitude fluctuations in the total multiplicity distributions or the shape of the pseudorapidity distributions are observed. We however find significant short-range multiplicity correlations in these data, that can be described as particle production in clusters. In Cu+Cu collisions, we observe large final-state azimuthal anisotropies ν2. A common scaling behavior for Cu+Cu and Au+Au for these anisotropies emerges when fluctuations in the initial state geometry are taken into account.

  19. Controlled cellular energy conversion in brown adipose tissue thermogenesis

    NASA Technical Reports Server (NTRS)

    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  20. Direct ribosomal binding by a cellular inhibitor of translation

    PubMed Central

    Colón-Ramos, Daniel A; Shenvi, Christina L; Weitzel, Douglas H; Gan, Eugene C; Matts, Robert; Cate, Jamie; Kornbluth, Sally

    2009-01-01

    During apoptosis and under conditions of cellular stress, several signaling pathways promote inhibition of cap-dependent translation while allowing continued translation of specific messenger RNAs encoding regulatory and stress-response proteins. We report here that the apoptotic regulator Reaper inhibits protein synthesis by binding directly to the 40S ribosomal subunit. This interaction does not affect either ribosomal association of initiation factors or formation of 43S or 48S complexes. Rather, it interferes with late initiation events upstream of 60S subunit joining, apparently modulating start-codon recognition during scanning. CrPV IRES–driven translation, involving direct ribosomal recruitment to the start site, is relatively insensitive to Reaper. Thus, Reaper is the first known cellular ribosomal binding factor with the potential to allow selective translation of mRNAs initiating at alternative start codons or from certain IRES elements. This function of Reaper may modulate gene expression programs to affect cell fate. PMID:16429152

  1. Common herbal remedies.

    PubMed

    Turkoski, B B

    2000-01-01

    Herbal remedies are becoming increasingly popular as people seek more effective, natural, or safer methods for treating a variety of complaints. As a result, nurses in every setting may expect to see increased numbers of patients who are using herbal products. When patients assume that the nurses will be critical of their use of herbals, they may withhold such information to avoid unpleasantness. This could place patients at risk for adverse effects, drug interactions, and complications related to ineffective treatment. Nurses who are knowledgeable about herbal products and who are open to discussion about these products can provide information and advice about safe use. The discussion in this article addresses actions, possible benefits, and dangers of the most common herbal products. Guidelines for assessing and teaching clients about herbal use are included. PMID:11062629

  2. CPL: Common Pipeline Library

    NASA Astrophysics Data System (ADS)

    ESO CPL Development Team

    2014-02-01

    The Common Pipeline Library (CPL) is a set of ISO-C libraries that provide a comprehensive, efficient and robust software toolkit to create automated astronomical data reduction pipelines. Though initially developed as a standardized way to build VLT instrument pipelines, the CPL may be more generally applied to any similar application. The code also provides a variety of general purpose image- and signal-processing functions, making it an excellent framework for the creation of more generic data handling packages. The CPL handles low-level data types (images, tables, matrices, strings, property lists, etc.) and medium-level data access methods (a simple data abstraction layer for FITS files). It also provides table organization and manipulation, keyword/value handling and management, and support for dynamic loading of recipe modules using programs such as EsoRex (ascl:1504.003).

  3. Life events and difficulties preceding stroke.

    PubMed Central

    House, A; Dennis, M; Mogridge, L; Hawton, K; Warlow, C

    1990-01-01

    Life events and difficulties were recorded for the year before stroke, using a standardised semi-structured interview, in 113 surviving patients seen after their first ever in a lifetime stroke. An age and sex-matched control group (n = 109) was also interviewed about the preceding year. The stroke patients reported fewer non-threatening events and events with only a short-term threat, while difficulties were reported with equal frequency by the two groups. However, events which were severely threatening in the long-term were significantly more common in the stroke patients (in the 52 weeks before stroke 26% versus 13%, odds ratio 2.3, 95% confidence interval 1.1-4.9). The increased rate was apparent throughout the year and not just in the weeks immediately before stroke onset. The number of stroke patients experiencing severe events in the follow up year fell to the level found in the control group. Recognised risk factors for stroke were found equally in those patients with and without severe events before onset, except that hypertension was rather less common in the patients who had experienced a severe event. It therefore appears that severe life events may be one of the determinants of stroke onset. PMID:2292691

  4. A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation

    PubMed Central

    Miller, Samuel I.; Chaudhary, Anu

    2016-01-01

    An understanding of common human diversity in innate immune pathways should be beneficial in understanding autoimmune diseases, susceptibility to infection, and choices of anti-inflammatory treatment. Such understanding could also result in definition of currently unknown components of human inflammation pathways. A cellular genome-wide association studies (GWAS) platform, termed Hi-HOST (High-throughput human in vitro susceptibility testing), was developed to assay in vitro cellular phenotypes of infection in genotyped lymphoblastoid cells from genetically diverse human populations. Hi-HOST allows for measurement of multiple host and pathogen parameters of infection/inflammation including: bacterial invasion and intracellular replication, host cell death, and cytokine production. Hi-HOST has been used to successfully define a significant portion of the heritable human diversity in inflammatory cell death in response to Salmonella typhimurium. It also led to the discovery of genetic variants important to protection against systemic inflammatory response syndrome (SIRS) and protection against death and bacteremia in individuals with SIRS. Our laboratory is currently using this platform to define human diversity in autophagy and the NLPR3 inflammasome pathways, and to define new components that can impact the expression of phenotypes related to these pathways. PMID:27128945

  5. A Cellular GWAS Approach to Define Human Variation in Cellular Pathways Important to Inflammation.

    PubMed

    Miller, Samuel I; Chaudhary, Anu

    2016-01-01

    An understanding of common human diversity in innate immune pathways should be beneficial in understanding autoimmune diseases, susceptibility to infection, and choices of anti-inflammatory treatment. Such understanding could also result in definition of currently unknown components of human inflammation pathways. A cellular genome-wide association studies (GWAS) platform, termed Hi-HOST (High-throughput human in vitro susceptibility testing), was developed to assay in vitro cellular phenotypes of infection in genotyped lymphoblastoid cells from genetically diverse human populations. Hi-HOST allows for measurement of multiple host and pathogen parameters of infection/inflammation including: bacterial invasion and intracellular replication, host cell death, and cytokine production. Hi-HOST has been used to successfully define a significant portion of the heritable human diversity in inflammatory cell death in response to Salmonella typhimurium. It also led to the discovery of genetic variants important to protection against systemic inflammatory response syndrome (SIRS) and protection against death and bacteremia in individuals with SIRS. Our laboratory is currently using this platform to define human diversity in autophagy and the NLPR3 inflammasome pathways, and to define new components that can impact the expression of phenotypes related to these pathways. PMID:27128945

  6. PKCλ/ι signaling—a common node for normal cellular development and breast oncogenesis

    PubMed Central

    Paul, Arindam; Paul, Soumen

    2015-01-01

    We recently demonstrated that PKCλ/ι signaling is an important contributor to breast cancer development. Strikingly, PKCλ/ι signaling is also important to balance self-renewal versus differentiation in pluripotent stem cells and is essential for embryonic development. This commentary highlights some key functions of PKCλ/ι signaling that are integral to both normal development and cancer progression. PMID:27308429

  7. Cellular Host Responses to Gliomas

    PubMed Central

    Barish, Michael E.; Garcia, Elizabeth; Metz, Marianne Z.; Myers, Sarah M.; Gutova, Margarita; Frank, Richard T.; Miletic, Hrvoje; Kendall, Stephen E.; Glackin, Carlotta A.; Bjerkvig, Rolf; Aboody, Karen S.

    2012-01-01

    Background Glioblastoma multiforme (GBM) is the most aggressive type of malignant primary brain tumors in adults. Molecular and genetic analysis has advanced our understanding of glioma biology, however mapping the cellular composition of the tumor microenvironment is crucial for understanding the pathology of this dreaded brain cancer. In this study we identified major cell populations attracted by glioma using orthotopic rodent models of human glioma xenografts. Marker-specific, anatomical and morphological analyses revealed a robust influx of host cells into the main tumor bed and tumor satellites. Methodology/Principal Findings Human glioma cell lines and glioma spheroid orthotopic implants were used in rodents. In both models, the xenografts recruited large numbers of host nestin-expressing cells, which formed a ‘network’ with glioma. The host nestin-expressing cells appeared to originate in the subventricular zone ipsilateral to the tumor, and were clearly distinguishable from pericytes that expressed smooth muscle actin. These distinct cell populations established close physical contact in a ‘pair-wise’ manner and migrated together to the deeper layers of tumor satellites and gave rise to tumor vasculature. The GBM biopsy xenografts displayed two different phenotypes: (a) low-generation tumors (first in vivo passage in rats) were highly invasive and non-angiogenic, and host nestin-positive cells that infiltrated into these tumors displayed astrocytic or elongated bipolar morphology; (b) high-generation xenografts (fifth passage) had pronounced cellularity, were angiogenic with ‘glomerulus-like’ microvascular proliferations that contained host nestin-positive cells. Stromal cell-derived factor-1 and its receptor CXCR4 were highly expressed in and around glioma xenografts, suggesting their role in glioma progression and invasion. Conclusions/Significance Our data demonstrate a robust migration of nestin-expressing host cells to glioma, which

  8. Host Event Based Network Monitoring

    SciTech Connect

    Jonathan Chugg

    2013-01-01

    The purpose of INL’s research on this project is to demonstrate the feasibility of a host event based network monitoring tool and the effects on host performance. Current host based network monitoring tools work on polling which can miss activity if it occurs between polls. Instead of polling, a tool could be developed that makes use of event APIs in the operating system to receive asynchronous notifications of network activity. Analysis and logging of these events will allow the tool to construct the complete real-time and historical network configuration of the host while the tool is running. This research focused on three major operating systems commonly used by SCADA systems: Linux, WindowsXP, and Windows7. Windows 7 offers two paths that have minimal impact on the system and should be seriously considered. First is the new Windows Event Logging API, and, second, Windows 7 offers the ALE API within WFP. Any future work should focus on these methods.

  9. Structures for common-cause failure analysis

    SciTech Connect

    Vaurio, J.K.

    1981-01-01

    Common-cause failure methodology and terminology have been reviewed and structured to provide a systematical basis for addressing and developing models and methods for quantification. The structure is based on (1) a specific set of definitions, (2) categories based on the way faults are attributable to a common cause, and (3) classes based on the time of entry and the time of elimination of the faults. The failure events are then characterized by their likelihood or frequency and the average residence time. The structure provides a basis for selecting computational models, collecting and evaluating data and assessing the importance of various failure types, and for developing effective defences against common-cause failure. The relationships of this and several other structures are described.

  10. Thermomechanical characterisation of cellular rubber

    NASA Astrophysics Data System (ADS)

    Seibert, H.; Scheffer, T.; Diebels, S.

    2016-01-01

    This contribution discusses an experimental possibility to characterise a cellular rubber in terms of the influence of multiaxiality, rate dependency under environmental temperature and its behaviour under hydrostatic pressure. In this context, a mixed open and closed cell rubber based on an ethylene propylene diene monomer is investigated exemplarily. The present article intends to give a general idea of the characterisation method and the considerable effects of this special type of material. The main focus lies on the experimental procedure and the used testing devices in combination with the analysis methods such as true three-dimensional digital image correlation. The structural compressibility is taken into account by an approach for a material model using the Theory of Porous Media with additional temperature dependence.

  11. Cellular ageing mechanisms in osteoarthritis.

    PubMed

    Sacitharan, P K; Vincent, T L

    2016-08-01

    Age is the strongest independent risk factor for the development of osteoarthritis (OA) and for many years this was assumed to be due to repetitive microtrauma of the joint surface over time, the so-called 'wear and tear' arthritis. As our understanding of OA pathogenesis has become more refined, it has changed our appreciation of the role of ageing on disease. Cartilage breakdown in disease is not a passive process but one involving induction and activation of specific matrix-degrading enzymes; chondrocytes are exquisitely sensitive to changes in the mechanical, inflammatory and metabolic environment of the joint; cartilage is continuously adapting to these changes by altering its matrix. Ageing influences all of these processes. In this review, we will discuss how ageing affects tissue structure, joint use and the cellular metabolism. We describe what is known about pathways implicated in ageing in other model systems and discuss the potential value of targeting these pathways in OA. PMID:27215642

  12. Pressure-actuated cellular structures.

    PubMed

    Pagitz, M; Lamacchia, E; Hol, J M A M

    2012-03-01

    Shape changing structures will play an important role in future engineering designs since rigid structures are usually only optimal for a small range of service conditions. Hence, a concept for reliable and energy-efficient morphing structures that possess a large strength to self-weight ratio would be widely applicable. We propose a novel concept for morphing structures that is inspired by the nastic movement of plants. The idea is to connect prismatic cells with tailored pentagonal and/or hexagonal cross sections such that the resulting cellular structure morphs into given target shapes for certain cell pressures. An efficient algorithm for computing equilibrium shapes as well as cross-sectional geometries is presented. The potential of this novel concept is demonstrated by several examples that range from a flagellum like propulsion device to a morphing aircraft wing. PMID:22278936

  13. Force generation by cellular motors.

    PubMed

    Wanka, Friedrich; Van Zoelen, Everardus J J

    2003-01-01

    Cell motility processes in non-muscle cells depend on the activity of motor proteins that bind to either microtubules or actin filaments. From presently available data it must be concluded that the driving force is generated by transient interaction of the respective motors with microtubules or actin filaments which then activates the binding and hydrolysis of ATP. This reaction results in an abrupt discharge of the motor molecule, the direction of which is determined by the spatial orientation of its binding to the helical and polar vehicle. The latter is thereby propelled in its length direction and simultaneously undergoes an axial rotation, while the expelled motor exerts an oppositely directed current in the surrounding fluid, comparable to jet propulsion. Force production, propulsion velocities and energy requirements known from in vitro studies comply with those derived from the theory. The theory opens new ways for the understanding of cellular activities such as particle transport, mitosis and morphodynamics. PMID:14668925

  14. Common Control System Vulnerability

    SciTech Connect

    Trent Nelson

    2005-12-01

    The Control Systems Security Program and other programs within the Idaho National Laboratory have discovered a vulnerability common to control systems in all sectors that allows an attacker to penetrate most control systems, spoof the operator, and gain full control of targeted system elements. This vulnerability has been identified on several systems that have been evaluated at INL, and in each case a 100% success rate of completing the attack paths that lead to full system compromise was observed. Since these systems are employed in multiple critical infrastructure sectors, this vulnerability is deemed common to control systems in all sectors. Modern control systems architectures can be considered analogous to today's information networks, and as such are usually approached by attackers using a common attack methodology to penetrate deeper and deeper into the network. This approach often is composed of several phases, including gaining access to the control network, reconnaissance, profiling of vulnerabilities, launching attacks, escalating privilege, maintaining access, and obscuring or removing information that indicates that an intruder was on the system. With irrefutable proof that an external attack can lead to a compromise of a computing resource on the organization's business local area network (LAN), access to the control network is usually considered the first phase in the attack plan. Once the attacker gains access to the control network through direct connections and/or the business LAN, the second phase of reconnaissance begins with traffic analysis within the control domain. Thus, the communications between the workstations and the field device controllers can be monitored and evaluated, allowing an attacker to capture, analyze, and evaluate the commands sent among the control equipment. Through manipulation of the communication protocols of control systems (a process generally referred to as ''reverse engineering''), an attacker can then map out the

  15. Cellular tolerance to pulsed heating

    NASA Astrophysics Data System (ADS)

    Simanovski, Dimitrii; Sarkar, M.; Irani, A.; O'Connell-Rodwell, C.; Contag, C.; Schwettman, H. Alan; Palanker, D.

    2005-04-01

    Many laser therapies involve significant heating of tissue with pulses varying from picoseconds to minutes in duration. In some of the applications heating is a primary goal, while in others it is an undesirable side effect. In both cases, if a hyperthermia is involved, the knowledge about the threshold temperature leading to irreversible cellular damage is critically important. We study the dependence of the threshold temperature on duration of the heat exposure in the range of 0.3 ms to 5 seconds. Thin layer of cells cultured in a Petri dish was exposed to a pulsed CO2 laser radiation. Laser beam was focused onto sample providing Gaussian intensity distribution in the focal plane with a beam diameter (2w) 2-10 mm. Surface temperature in the central part of the focal spot (1mm in diameter) was measured by thermal infrared (IR) emission from the sample, recorded with a fast IR detector. For pulses shorter than 1 s the temperature profile across the focal spot was found to closely correspond to the radial distribution of the laser beam intensity, thus allowing for accurate determination of temperature at any given distance from the center of the spot. Immediate cellular damage was assessed using vital staining with the live/dead fluorescent assay. Threshold temperatures were found to vary from 65 °C at 5 s of heating to 160 °C at pulses of 0.3 ms in duration. The shorter end of this range was limited by vaporization, which occurs during the laser pulse and results in mechanical damage to cells. Dependence of the maximal temperature on pulse duration could be approximated by Arrhenius law with activation energy being about 1 eV.

  16. Fundamental Limits to Cellular Sensing

    NASA Astrophysics Data System (ADS)

    ten Wolde, Pieter Rein; Becker, Nils B.; Ouldridge, Thomas E.; Mugler, Andrew

    2016-03-01

    In recent years experiments have demonstrated that living cells can measure low chemical concentrations with high precision, and much progress has been made in understanding what sets the fundamental limit to the precision of chemical sensing. Chemical concentration measurements start with the binding of ligand molecules to receptor proteins, which is an inherently noisy process, especially at low concentrations. The signaling networks that transmit the information on the ligand concentration from the receptors into the cell have to filter this receptor input noise as much as possible. These networks, however, are also intrinsically stochastic in nature, which means that they will also add noise to the transmitted signal. In this review, we will first discuss how the diffusive transport and binding of ligand to the receptor sets the receptor correlation time, which is the timescale over which fluctuations in the state of the receptor, arising from the stochastic receptor-ligand binding, decay. We then describe how downstream signaling pathways integrate these receptor-state fluctuations, and how the number of receptors, the receptor correlation time, and the effective integration time set by the downstream network, together impose a fundamental limit on the precision of sensing. We then discuss how cells can remove the receptor input noise while simultaneously suppressing the intrinsic noise in the signaling network. We describe why this mechanism of time integration requires three classes (groups) of resources—receptors and their integration time, readout molecules, energy—and how each resource class sets a fundamental sensing limit. We also briefly discuss the scheme of maximum-likelihood estimation, the role of receptor cooperativity, and how cellular copy protocols differ from canonical copy protocols typically considered in the computational literature, explaining why cellular sensing systems can never reach the Landauer limit on the optimal trade

  17. The Common Land Model.

    NASA Astrophysics Data System (ADS)

    Dai, Yongjiu; Zeng, Xubin; Dickinson, Robert E.; Baker, Ian; Bonan, Gordon B.; Bosilovich, Michael G.; Denning, A. Scott; Dirmeyer, Paul A.; Houser, Paul R.; Niu, Guoyue; Oleson, Keith W.; Schlosser, C. Adam; Yang, Zong-Liang

    2003-08-01

    The Common Land Model (CLM) was developed for community use by a grassroots collaboration of scientists who have an interest in making a general land model available for public use and further development. The major model characteristics include enough unevenly spaced layers to adequately represent soil temperature and soil moisture, and a multilayer parameterization of snow processes; an explicit treatment of the mass of liquid water and ice water and their phase change within the snow and soil system; a runoff parameterization following the TOPMODEL concept; a canopy photosynthesis-conductance model that describes the simultaneous transfer of CO2 and water vapor into and out of vegetation; and a tiled treatment of the subgrid fraction of energy and water balance. CLM has been extensively evaluated in offline mode and coupling runs with the NCAR Community Climate Model (CCM3). The results of two offline runs, presented as examples, are compared with observations and with the simulation of three other land models [the Biosphere-Atmosphere Transfer Scheme (BATS), Bonan's Land Surface Model (LSM), and the 1994 version of the Chinese Academy of Sciences Institute of Atmospheric Physics LSM (IAP94)].

  18. Cellular Senescence and the Biology of Aging, Disease, and Frailty.

    PubMed

    LeBrasseur, Nathan K; Tchkonia, Tamara; Kirkland, James L

    2015-01-01

    Population aging simultaneously highlights the remarkable advances in science, medicine, and public policy, and the formidable challenges facing society. Indeed, aging is the primary risk factor for many of the most common chronic diseases and frailty, which result in profound social and economic costs. Population aging also reveals an opportunity, i.e. interventions to disrupt the fundamental biology of aging could significantly delay the onset of age-related conditions as a group, and, as a result, extend the healthy life span, or health span. There is now considerable evidence that cellular senescence is an underlying mechanism of aging and age-related conditions. Cellular senescence is a process in which cells lose the ability to divide and damage neighboring cells by the factors they secrete, collectively referred to as the senescence-associated secretory phenotype (SASP). Herein, we discuss the concept of cellular senescence, review the evidence that implicates cellular senescence and SASP in age-related deterioration, hyperproliferation, and inflammation, and propose that this underlying mechanism of aging may play a fundamental role in the biology of frailty. PMID:26485647

  19. Returning common sense to regulations

    SciTech Connect

    Fox, M.R.

    1995-10-01

    While these sessions of the November 1995 meeting of the American Nuclear Society are being devoted to the Linear Theory of harm from radiation, it must be realized that the low-level radiation issue, as important as it may be, is but a subset of an entire body of environmental issues running afoul of common sense. Cellular phones, electromagnetic fields, asbestos, dioxin, acid rain, and others especially in their public portrayals, some in their regulatory treatment, are based upon exaggerated or misunderstood risks. One must recognize that what lies ahead is an immense effort to revisit the underlying science of the existing regulations of radiation exposures. New evidence has been published, and most importantly, it is now recognized that many of these regulations--promulgated with the best of intentions--have been extraordinarily harmful to the public. In many cases, the harm has been exaggerated, and has created in the public policy arena the notion that the public is at great risk from the smallest sources of radiation. The national cost of compliance with these regulations has been enormous. To the extent that existing environmental regulations are not being moderated, they pose major economic threats to present and future industries involving nuclear materials and technology. These would include the pharmaceutical industries as well as those seeking U.S. isotope markets in separations, purification, labeling, and manufacturing of new radiopharmaceuticals for cancer therapy, diagnosis, pain mitigation, treatment of arthritis, and other new applications. For those who are not aware of the results of recent advances in radiopharmaceuticals, clinical trials have demonstrated an 80% remission rate in the treatment of b-cell lymphoma and leukemia. New isotopes and new isotope technology promise greater effectiveness in the treatment of cancer and other diseases. The regulatory problems and their enormous costs exist at all stages in nuclear medicine, from the

  20. Bacterial Cellular Materials as Precursors of Chloroform

    NASA Astrophysics Data System (ADS)

    Wang, J.; Ng, T.; Zhang, Q.; Chow, A. T.; Wong, P.

    2011-12-01

    The environmental sources of chloroform and other halocarbons have been intensively investigated because their effects of stratospheric ozone destruction and environmental toxicity. It has been demonstrated that microorganisms could facilitate the biotic generation of chloroform from natural organic matters in soil, but whether the cellular materials itself also serves as an important precursor due to photo-disinfection is poorly known. Herein, seven common pure bacterial cultures (Acinetobacter junii, Aeromonas hydrophila, Bacillus cereus, Bacillus substilis, Escherichia coli, Shigella sonnei, Staphylococcus sciuri) were chlorinated to evaluate the yields of chloroform, dibromochloromethane, dichlorobromomethane, and bromoform. The effects of bromide on these chemical productions and speciations were also investigated. Results showed that, on average, 5.64-36.42 μg-chloroform /mg-C were generated during the bacterial chlorination, in similar order of magnitude to that generated by humic acid (previously reported as 78 μg-chloroform/mg-C). However, unlike humic acid in water chlorination, chloroform concentration did not simply increase with the total organic carbon in water mixture. In the presence of bromide, the yield of brominated species responded linearly to the bromide concentration. This study provides useful information to understand the contributions of chloroform from photodisinfection processes in coastal environments.

  1. A structural basis for cellular senescence

    PubMed Central

    Aranda-Anzaldo, Armando

    2009-01-01

    Replicative senescence (RS) that limits the proliferating potential of normal eukaryotic cells occurs either by a cell-division counting mechanism linked to telomere erosion or prematurely through induction by cell stressors such as oncogene hyper-activation. However, there is evidence that RS also occurs by a stochastic process that is independent of number of cell divisions or cellular stress and yet it leads to a highly-stable, non-reversible post-mitotic state that may be long-lasting and that such a process is widely represented among higher eukaryotes. Here I present and discuss evidence that the interactions between DNA and the nuclear substructure, commonly known as the nuclear matrix, define a higher-order structure within the cell nucleus that following thermodynamic constraints, stochastically evolves towards maximum stability, thus becoming limiting for mitosis to occur. It is suggested that this process is responsible for ultimate replicative senescence and yet it is compatible with long-term cell survival. PMID:20157542

  2. Functional and cellular adaptations of rodent skeletal muscle to weightlessness

    NASA Technical Reports Server (NTRS)

    Caiozzo, Vincent J.; Haddad, Fadia; Baker, Michael J.; Baldwin, Kenneth M.

    1995-01-01

    This paper describes the affects of microgravity upon three key cellular levels (functional, protein, and mRNA) that are linked to one another. It is clear that at each of these levels, microgravity produces rapid and substantial alterations. One of the key challenges facing the life science community is the development of effective countermeasures that prevent the loss of muscle function as described in this paper. The development of optimal countermeasures, however, awaits a clearer understanding of events occurring at the levels of transcription, translation, and degradation.

  3. The molecular and cellular biology of enhanced cognition

    PubMed Central

    Lee, Yong-Seok; Silva, Alcino J.

    2009-01-01

    Most molecular and cellular studies of cognitive function have focused on either normal or pathological states, but recent research with transgenic mice has started to address the mechanisms of enhanced cognition. These results point to key synaptic and nuclear signalling events that can be manipulated to facilitate the induction or increase the stability of synaptic plasticity, and therefore enhance the acquisition or retention of information. Here, we review these surprising findings and explore their implications to both mechanisms of learning and memory and to ongoing efforts to develop treatments for cognitive disorders. These findings represent the beginning of a fundamental new approach in the study of enhanced cognition. PMID:19153576

  4. Incisive Imaging and Computation for Cellular Mysteries: Lessons from Abscission

    PubMed Central

    Elia, Natalie; Ott, Carolyn; Lippincott-Schwartz, Jennifer

    2014-01-01

    The final cleavage event that terminates cell division, abscission of the small, dense intercellular bridge, has been particularly challenging to resolve. Here, we describe imaging innovations that helped answer long-standing questions about the mechanism of abscission. We further explain how computational modeling of high-resolution data was employed to test hypotheses and generate additional insights. We present the model that emerges from application of these complimentary approaches. Similar experimental strategies will undoubtedly reveal exciting details about other underresolved cellular structures. PMID:24315094

  5. Inhibitors – cellular aspects and novel approaches for tolerance

    PubMed Central

    SCOTT, D. W.

    2014-01-01

    Summary The immune response against therapeutic clotting factors VIII and IX (FVIII and FIX) is a major adverse event that can effectively thwart their effectiveness in correcting bleeding disorders. Thus, a significant number of haemophilia patients form antibodies, called inhibitors, which neutralize the procoagulant functions of therapeutic cofactors FVIII (haemophilia A) or FIX (haemophilia B). Understanding the cellular and molecular aspects of inhibitor formation is critical to designing tolerogenic therapies for clinical use. This review will focus on the basis of the immune response to FVIII, in particular, and will discuss emerging efforts to not only reduce immunogenicity but also to prevent and/or reverse inhibitor formation. PMID:24762281

  6. [Cellular senescence and pulmonary disease: COPD as an example].

    PubMed

    Boyer, L; Savale, L; Boczkowski, J; Adnot, S

    2014-12-01

    The biological mechanisms of aging, and more specifically cellular senescence, are increasingly a subject of research. Cellular senescence may be a common determinant of many age-related diseases, including some chronic lung diseases such as chronic obstructive pulmonary disease (COPD) or idiopathic pulmonary fibrosis. Many arguments suggest that these diseases are associated with premature senescence of lung cells, which may be involved in the pathophysiology of respiratory alterations. Furthermore, these diseases are associated with systemic manifestations, such as bone loss, muscle wasting and atherosclerosis, which impact on symptoms and prognosis. Whether these alterations are related to a common pathogenic mechanism or develop independently in patients with COPD remains an open question. In this review, we will focus on cellular senescence and COPD. Two concepts will be discussed: (1) the role of cell senescence in the pathophysiology of lung destruction, vascular remodeling and inflammation in COPD, (2) the possible link between the pulmonary and systemic manifestations of COPD which could reflect a general process of accelerated aging. PMID:25496787

  7. Direct interaction of cellular hnRNP-F and NS1 of influenza A virus accelerates viral replication by modulation of viral transcriptional activity and host gene expression

    SciTech Connect

    Lee, Jun Han; Kim, Sung-Hak; Pascua, Philippe Noriel Q.; Song, Min-Suk; Baek, Yun Hee; Jin, Xun; Choi, Joong-Kook; Kim, Chul-Joong; Kim, Hyunggee; Choi, Young Ki

    2010-02-05

    To investigate novel NS1-interacting proteins, we conducted a yeast two-hybrid analysis, followed by co-immunoprecipitation assays. We identified heterogeneous nuclear ribonucleoprotein F (hnRNP-F) as a cellular protein interacting with NS1 during influenza A virus infection. Co-precipitation assays suggest that interaction between hnRNP-F and NS1 is a common and direct event among human or avian influenza viruses. NS1 and hnRNP-F co-localize in the nucleus of host cells, and the RNA-binding domain of NS1 directly interacts with the GY-rich region of hnRNP-F determined by GST pull-down assays with truncated proteins. Importantly, hnRNP-F expression levels in host cells indicate regulatory role on virus replication. hnRNP-F depletion by small interfering RNA (siRNA) shows 10- to 100-fold increases in virus titers corresponding to enhanced viral RNA polymerase activity. Our results delineate novel mechanism of action by which NS1 accelerates influenza virus replication by modulating normal cellular mRNA processes through direct interaction with cellular hnRNP-F protein.

  8. Threads of common knowledge.

    PubMed

    Icamina, P

    1993-04-01

    Indigenous knowledge is examined as it is affected by development and scientific exploration. The indigenous culture of shamanism, which originated in northern and southeast Asia, is a "political and religious technique for managing societies through rituals, myths, and world views." There is respect for the natural environment and community life as a social common good. This world view is still practiced by many in Latin America and in Colombia specifically. Colombian shamanism has an environmental accounting system, but the Brazilian government has established its own system of land tenure and political representation which does not adequately represent shamanism. In 1992 a conference was held in the Philippines by the International Institute for Rural Reconstruction and IDRC on sustainable development and indigenous knowledge. The link between the two is necessary. Unfortunately, there are already examples in the Philippines of loss of traditional crop diversity after the introduction of modern farming techniques and new crop varieties. An attempt was made to collect species, but without proper identification. Opposition was expressed to the preservation of wilderness preserves; the desire was to allow indigenous people to maintain their homeland and use their time-tested sustainable resource management strategies. Property rights were also discussed during the conference. Of particular concern was the protection of knowledge rights about biological diversity or pharmaceutical properties of indigenous plant species. The original owners and keepers of the knowledge must retain access and control. The research gaps were identified and found to be expansive. Reference was made to a study of Mexican Indian children who knew 138 plant species while non-Indian children knew only 37. Sometimes there is conflict of interest where foresters prefer timber forests and farmers desire fuelwood supplies and fodder and grazing land, which is provided by shrubland. Information

  9. Dialogue on private events

    PubMed Central

    Palmer, David C.; Eshleman, John; Brandon, Paul; Layng, T. V. Joe; McDonough, Christopher; Michael, Jack; Schoneberger, Ted; Stemmer, Nathan; Weitzman, Ray; Normand, Matthew

    2004-01-01

    In the fall of 2003, the authors corresponded on the topic of private events on the listserv of the Verbal Behavior Special Interest Group. Extracts from that correspondence raised questions about the role of response amplitude in determining units of analysis, whether private events can be investigated directly, and whether covert behavior differs from other behavior except in amplitude. Most participants took a cautious stance, noting not only conceptual pitfalls and empirical difficulties in the study of private events, but doubting the value of interpretive exercises about them. Others argued that despite such obstacles, in domains where experimental analyses cannot be done, interpretation of private events in the light of laboratory principles is the best that science can offer. One participant suggested that the notion that private events can be behavioral in nature be abandoned entirely; as an alternative, the phenomena should be reinterpreted only as physiological events. PMID:22477293

  10. Cellular phones: are they detrimental?

    PubMed

    Salama, Osama E; Abou El Naga, Randa M

    2004-01-01

    The issue of possible health effects of cellular phones is very much alive in the public's mind where the rapid increase in the number of the users of cell phones in the last decade has increased the exposure of people to the electromagnetic fields (EMFs). Health consequences of long term use of mobile phones are not known in detail but available data indicates the development of non specific annoying symptoms on acute exposure to mobile phone radiations. In an attempt to determine the prevalence of such cell phones associated health manifestations and the factors affecting their occurrence, a cross sectional study was conducted in five randomly selected faculties of Alexandria University. Where, 300 individuals including teaching staff, students and literate employee were equally allocated and randomly selected among the five faculties. Data about mobile phone's users and their medical history, their pattern of mobile usage and the possible deleterious health manifestations associated with cellular phone use was collected. The results revealed 68% prevalence of mobile phone usage, nearly three quarters of them (72.5%) were complainers of the health manifestations. They suffered from headache (43%), earache (38.3%), sense of fatigue (31.6%), sleep disturbance (29.5%), concentration difficulty (28.5%) and face burning sensation (19.2%). Both univariate and multivariate analysis were consistent in their findings. Symptomatic users were found to have significantly higher frequency of calls/day, longer call duration and longer total duration of mobile phone usage/day than non symptomatic users. For headache both call duration and frequency of calls/day were the significant predicting factors for its occurrence (chi2 = 18.208, p = 0.0001). For earache, in addition to call duration, the longer period of owning the mobile phone were significant predictors (chi2 = 16.996, p = 0.0002). Sense of fatigue was significantly affected by both call duration and age of the user

  11. Survey of cellular radiosensitivity parameters.

    PubMed

    Katz, R; Zachariah, R; Cucinotta, F A; Zhang, C

    1994-12-01

    A model of the formation of particle tracks in emulsion has been extended through the use of biological target theory to formulate a theory of the response of biological cells and molecules of biological importance to irradiation with energetic heavy ions. For this purpose the response to gamma rays is represented by the single-hit, multitarget model with parameters m and D0, while additional parameters kappa (or a0) and sigma 0 are required to represent the size of internal cellular targets and the effective cross-sectional area of the cell nucleus, respectively, for heavy-ion bombardments. For one-or-more-hit detectors, only the first three of these parameters are required and m = 1. For cells m is typically 2 or more. The model is developed from the concept that response to secondary electrons follows the same functional form for gamma rays and for the gamma rays surrounding an ion's path. Originally applied to dry enzymes and viruses in 1967, the model of the one-hit detector has been extended to emulsions, to other physical and chemical detectors, to single- and double-strand breaks in DNA in EO buffer and to three E. coli strains. The two-hit response has been observed for "track core" effects in radiation chemistry, for supralinearity in thermoluminescent dosimeters and for desensitized nuclear emulsions, where hit numbers up to 6 have been observed. In its extension to biological cells, additional concepts are required relating to the character of the track, namely the grain-count and track-width regimes, and to the ability of multitarget systems to acquire damage from intertrack delta rays (called gamma kill) as well as from intratrack delta rays (called ion kill). The model has been applied to some 40 sets of radiobiological data obtained from gamma, track-segment heavy-ion and neutron irradiations. Here we elaborate on the meaning of these concepts, tabulate the cellular parameters, and display their systematic behavior and the relationships among them

  12. HOW COMMON IS RSI?

    PubMed Central

    Palmer, Keith T; Reading, Isabel; Calnan, Michael; Coggon, David

    2013-01-01

    Objective Statistics from Labour Force Surveys are widely quoted as evidence for the scale of occupational illness in Europe. However, occupational attribution depends on whether participants believe their health problem is caused or aggravated by work, and personal beliefs may be unreliable. We assessed the potential for error for work-associated arm pain. Methods We mailed a questionnaire to working-aged adults, randomly chosen from five British general practices. We asked about: occupational activities; mental health; self-rated health; arm pain; and beliefs about its causation. Those in work (n = 1769) were asked about activities likely to cause arm pain, from which we derived a variable for exposure to any ‘arm-straining’ occupational activity. We estimated the relative risk (RR) from arm-straining activity, using a modified Cox model, and derived the population attributable fraction (PAF). We compared the proportion of arm pain cases reporting their symptom as caused or made worse by work with the calculated PAF, overall and for subsets defined by demographic and other characteristics. Results Arm pain in the past year was more common in the 1,143 subjects who reported exposure to arm-straining occupational activity (RR 1.2, 95% confidence interval 1.1 to 1.5). In the study sample as a whole, 53.9% of 817 cases reported their arm pain as work-associated, whereas the PAF for arm-straining occupational activity was only 13.9%. The ratio of cases reported as work-related to the calculated attributable number was substantially higher below 50 years (5.4) than at older ages (3.0) and higher in those with worse self-rated and mental health. Conclusions Counting people with arm pain which they believe to be work-related can overestimate the number of cases attributable to work substantially. This casts doubt on the validity of a major source of information used by European Governments to evaluate their occupational health strategies. PMID:18056747

  13. Autophagy in the cellular energetic balance.

    PubMed

    Singh, Rajat; Cuervo, Ana Maria

    2011-05-01

    Autophagy mediates the degradation of cellular components in lysosomes, assuring removal of altered or dysfunctional proteins and organelles. Autophagy is not only activated in response to cellular damage; in fact, one of its strongest and better-characterized stimuli is starvation. Activation of autophagy when nutrients are scarce allows cells to reutilize their own constituents for energy. Besides protein breakdown, autophagy also contributes to the mobilization of diverse cellular energy stores. This recently discovered interplay between autophagy and lipid and carbohydrate metabolism reveals the existence of a dynamic feedback between autophagy and cellular energy balance. PMID:21531332

  14. Integration of mobile satellite and cellular systems

    NASA Technical Reports Server (NTRS)

    Drucker, Elliott H.; Estabrook, Polly; Pinck, Deborah; Ekroot, Laura

    1993-01-01

    By integrating the ground based infrastructure component of a mobile satellite system with the infrastructure systems of terrestrial 800 MHz cellular service providers, a seamless network of universal coverage can be established. Users equipped for both cellular and satellite service can take advantage of a number of features made possible by such integration, including seamless handoff and universal roaming. To provide maximum benefit at lowest posible cost, the means by which these systems are integrated must be carefully considered. Mobile satellite hub stations must be configured to efficiently interface with cellular Mobile Telephone Switching Offices (MTSO's), and cost effective mobile units that provide both cellular and satellite capability must be developed.

  15. Review of cellular mechanotransduction on micropost substrates.

    PubMed

    Geng, Yuxu; Wang, Zhanjiang

    2016-03-01

    As physical entities, living cells can sense and respond to various stimulations within and outside the body through cellular mechanotransduction. Any deviation in cellular mechanotransduction will not only undermine the orchestrated regulation of mechanical responses, but also lead to the breakdown of their physiological function. Therefore, a quantitative study of cellular mechanotransduction needs to be conducted both in experiments and in computational simulations to investigate the underlying mechanisms of cellular mechanotransduction. In this review, we present an overview of the current knowledge and significant progress in cellular mechanotransduction via micropost substrates. In the aspect of experimental studies, we summarize significant experimental progress and place an emphasis on the coupled relationship among cellular spreading, focal adhesion and contractility as well as the influence of substrate properties on force-involved cellular behaviors. In the other aspect of computational investigations, we outline a coupled framework including the biochemically motivated stress fiber model and thermodynamically motivated adhesion model and present their predicted biomechanical responses and then compare predicted simulation results with experimental observations to further explore the mechanisms of cellular mechanotransduction. At last, we discuss the future perspectives both in experimental technologies and in computational models, as well as facing challenges in the area of cellular mechanotransduction. PMID:26245253

  16. Bacterial Cellular Engineering by Genome Editing and Gene Silencing

    PubMed Central

    Nakashima, Nobutaka; Miyazaki, Kentaro

    2014-01-01

    Genome editing is an important technology for bacterial cellular engineering, which is commonly conducted by homologous recombination-based procedures, including gene knockout (disruption), knock-in (insertion), and allelic exchange. In addition, some new recombination-independent approaches have emerged that utilize catalytic RNAs, artificial nucleases, nucleic acid analogs, and peptide nucleic acids. Apart from these methods, which directly modify the genomic structure, an alternative approach is to conditionally modify the gene expression profile at the posttranscriptional level without altering the genomes. This is performed by expressing antisense RNAs to knock down (silence) target mRNAs in vivo. This review describes the features and recent advances on methods used in genomic engineering and silencing technologies that are advantageously used for bacterial cellular engineering. PMID:24552876

  17. A palette of fluorescent proteins optimized for diverse cellular environments

    PubMed Central

    Costantini, Lindsey M.; Baloban, Mikhail; Markwardt, Michele L.; Rizzo, Mark; Guo, Feng; Verkhusha, Vladislav V.; Snapp, Erik L.

    2015-01-01

    To perform quantitative live cell imaging, investigators require fluorescent reporters that accurately report protein localization and levels, while minimally perturbing the cell. Yet, within the biochemically distinct environments of cellular organelles, popular fluorescent proteins (FPs), including EGFP, can be unreliable for quantitative imaging, resulting in underestimation of protein levels and incorrect localization. Specifically, within the secretory pathway, significant populations of FPs misfold and fail to fluoresce due to non-native disulphide bond formation. Furthermore, transmembrane FP fusion constructs can disrupt organelle architecture due to oligomerizing tendencies of numerous common FPs. Here, we describe a powerful set of bright and inert FPs optimized for use in multiple cellular compartments, especially oxidizing environments and biological membranes. Also, we provide new insights into use of red FPs in the secretory pathway. Our monomeric "oxFPs" finally resolve long standing, underappreciated, and important problems of cell biology and should be useful for a number of applications. PMID:26158227

  18. [Photodynamic modulation of cellular functions].

    PubMed

    Li, Yuan; Jiang, Hong-Ning; Cui, Zong-Jie

    2016-08-25

    Photodynamic action, due to the rather limited lifetime (1 μs) and effective reactive distance of singlet oxygen (< 10 nm), could subcellular-specifically regulate different cellular functions. Photodynamic action could activate permanently cholecystokinin (CCK) 1 receptors, and sensitize or desensitize other G protein-coupled receptors. The emergence in recent years of genetically- encoded protein photosensitisers has enabled more precisely-targeted photodynamic modulation of subcellular organelles and functional proteins. Protein photosensitisers (such as KillerRed, miniSOG or SOPP) expressed on the plasma membrane, mitochondria, lysosomes or endoplasmic reticulum can modulate photodynamically subcellular functions and fine-tune protein activity by targeted photooxidation. With the newly emerged active illumination technique, simultaneous photodynamic action localized at multiple sites is now possible, and the contribution of subcellular regions to the whole cell or individual cells to a cell cluster could be quantitated. Photodynamic action with protein photosensitiser will be a powerful tool for nano-manipulation in cell physiology research. PMID:27546513

  19. Efficiency of cellular information processing

    NASA Astrophysics Data System (ADS)

    Barato, Andre C.; Hartich, David; Seifert, Udo

    2014-10-01

    We show that a rate of conditional Shannon entropy reduction, characterizing the learning of an internal process about an external process, is bounded by the thermodynamic entropy production. This approach allows for the definition of an informational efficiency that can be used to study cellular information processing. We analyze three models of increasing complexity inspired by the Escherichia coli sensory network, where the external process is an external ligand concentration jumping between two values. We start with a simple model for which ATP must be consumed so that a protein inside the cell can learn about the external concentration. With a second model for a single receptor we show that the rate at which the receptor learns about the external environment can be nonzero even without any dissipation inside the cell since chemical work done by the external process compensates for this learning rate. The third model is more complete, also containing adaptation. For this model we show inter alia that a bacterium in an environment that changes at a very slow time-scale is quite inefficient, dissipating much more than it learns. Using the concept of a coarse-grained learning rate, we show for the model with adaptation that while the activity learns about the external signal the option of changing the methylation level increases the concentration range for which the learning rate is substantial.

  20. Illuminating cellular physiology: recent developments.

    PubMed

    Brovko, Lubov Y; Griffiths, Mansel W

    2007-01-01

    Bioluminescent methods are gaining more and more attention among scientists due to their sensitivity, selectivity and simplicity; coupled with the fact that the bioluminescence can be monitored both in vitro and in vivo. Since the discovery of bioluminescence in the 19th century, enzymes involved in the bioluminescent process have been isolated and cloned. The bioluminescent reactions in several different organisms have also been fully characterized and used as reporters in a wide variety of biochemical assays. From the 1990s it became clear that bioluminescence can be detected and quantified directly from inside a living cell. This gave rise to numerous possibilities for the in vivo monitoring of intracellular processes non-invasively using bioluminescent molecules as reporters. This review describes recent developments in the area of bioluminescent imaging for cell biology. Newly developed imaging methods allow transcriptional/translational regulation, signal transduction, protein-protein interaction, oncogenic transformation, cell and protein trafficking, and target drug action to be monitored in vivo in real-time with high temporal and spatial resolution; thus providing researchers with priceless information on cellular functions. Advantages and limitations of these novel bioluminescent methods are discussed and possible future developments identified. PMID:17725230

  1. Predicting and Analyzing Cellular Networks

    NASA Astrophysics Data System (ADS)

    Singh, Mona

    High-throughput experimental technologies, along with computational predictions, have resulted in large-scale biological networks for numerous organisms. Global analyses of biological networks provide new opportunities for revealing protein functions and pathways, and for uncovering cellular organization principles. In my talk, I will discuss a number of approaches we have developed over the years for the complementary problems of predicting interactions and analyzing interaction networks. First, I will describe a genomic approach for uncovering high-confidence regulatory interactions, and show how it can be effectively combined with a framework for predicting regulatory interactions for proteins with known structural domains but unknown binding specificity. Next, I will describe algorithms for analyzing protein interaction networks in order to uncover protein function and functional modules, and demonstrate the importance of considering the topological structure of interaction networks in order to make high quality predictions. Finally, I will present a framework for explicitly incorporating known attributes of individual proteins into the analysis of biological networks, and utilize it to discover recurring network patterns underlying a range of biological processes.

  2. Use of cellular telephones and transmission of pathogens by medical staff in New York and Israel.

    PubMed

    Goldblatt, Joseph Gil; Krief, Iris; Klonsky, Tal; Haller, Daniel; Milloul, Victor; Sixsmith, Diane M; Srugo, Isaac; Potasman, Israel

    2007-04-01

    Hands and instruments used by healthcare workers may serve as vectors for the nosocomial transmission of microorganisms. The use of cellular telephones by medical personnel and the associated nosocomial transmission of pathogens have not been thoroughly examined. Findings from our study show that cellular telephones are commonly used by hospital personnel, even during patient contact. One-fifth of the cellular telephones examined in this study were found to harbor pathogenic microorganisms, showing that these devices may serve as vectors for transmission to patients. PMID:17385162

  3. Millimeter-Wave Evolution for 5G Cellular Networks

    NASA Astrophysics Data System (ADS)

    Sakaguchi, Kei; Tran, Gia Khanh; Shimodaira, Hidekazu; Nanba, Shinobu; Sakurai, Toshiaki; Takinami, Koji; Siaud, Isabelle; Strinati, Emilio Calvanese; Capone, Antonio; Karls, Ingolf; Arefi, Reza; Haustein, Thomas

    Triggered by the explosion of mobile traffic, 5G (5th Generation) cellular network requires evolution to increase the system rate 1000 times higher than the current systems in 10 years. Motivated by this common problem, there are several studies to integrate mm-wave access into current cellular networks as multi-band heterogeneous networks to exploit the ultra-wideband aspect of the mm-wave band. The authors of this paper have proposed comprehensive architecture of cellular networks with mm-wave access, where mm-wave small cell basestations and a conventional macro basestation are connected to Centralized-RAN (C-RAN) to effectively operate the system by enabling power efficient seamless handover as well as centralized resource control including dynamic cell structuring to match the limited coverage of mm-wave access with high traffic user locations via user-plane/control-plane splitting. In this paper, to prove the effectiveness of the proposed 5G cellular networks with mm-wave access, system level simulation is conducted by introducing an expected future traffic model, a measurement based mm-wave propagation model, and a centralized cell association algorithm by exploiting the C-RAN architecture. The numerical results show the effectiveness of the proposed network to realize 1000 times higher system rate than the current network in 10 years which is not achieved by the small cells using commonly considered 3.5 GHz band. Furthermore, the paper also gives latest status of mm-wave devices and regulations to show the feasibility of using mm-wave in the 5G systems.

  4. Global Self-Organization of the Cellular Metabolic Structure

    PubMed Central

    De La Fuente, Ildefonso M.; Martínez, Luis; Pérez-Samartín, Alberto L.; Ormaetxea, Leire; Amezaga, Cristian; Vera-López, Antonio

    2008-01-01

    Background Over many years, it has been assumed that enzymes work either in an isolated way, or organized in small catalytic groups. Several studies performed using “metabolic networks models” are helping to understand the degree of functional complexity that characterizes enzymatic dynamic systems. In a previous work, we used “dissipative metabolic networks” (DMNs) to show that enzymes can present a self-organized global functional structure, in which several sets of enzymes are always in an active state, whereas the rest of molecular catalytic sets exhibit dynamics of on-off changing states. We suggested that this kind of global metabolic dynamics might be a genuine and universal functional configuration of the cellular metabolic structure, common to all living cells. Later, a different group has shown experimentally that this kind of functional structure does, indeed, exist in several microorganisms. Methodology/Principal Findings Here we have analyzed around 2.500.000 different DMNs in order to investigate the underlying mechanism of this dynamic global configuration. The numerical analyses that we have performed show that this global configuration is an emergent property inherent to the cellular metabolic dynamics. Concretely, we have found that the existence of a high number of enzymatic subsystems belonging to the DMNs is the fundamental element for the spontaneous emergence of a functional reactive structure characterized by a metabolic core formed by several sets of enzymes always in an active state. Conclusions/Significance This self-organized dynamic structure seems to be an intrinsic characteristic of metabolism, common to all living cellular organisms. To better understand cellular functionality, it will be crucial to structurally characterize these enzymatic self-organized global structures. PMID:18769681

  5. Features, Events, and Processes: Disruptive Events

    SciTech Connect

    J. King

    2004-03-31

    The primary purpose of this analysis is to evaluate seismic- and igneous-related features, events, and processes (FEPs). These FEPs represent areas of natural system processes that have the potential to produce disruptive events (DE) that could impact repository performance and are related to the geologic processes of tectonism, structural deformation, seismicity, and igneous activity. Collectively, they are referred to as the DE FEPs. This evaluation determines which of the DE FEPs are excluded from modeling used to support the total system performance assessment for license application (TSPA-LA). The evaluation is based on the data and results presented in supporting analysis reports, model reports, technical information, or corroborative documents that are cited in the individual FEP discussions in Section 6.2 of this analysis report.

  6. Event-by-Event Fission with FREYA

    SciTech Connect

    Randrup, J; Vogt, R

    2010-11-09

    The recently developed code FREYA (Fission Reaction Event Yield Algorithm) generates large samples of complete fission events, consisting of two receding product nuclei as well as a number of neutrons and photons, all with complete kinematic information. Thus it is possible to calculate arbitrary correlation observables whose behavior may provide unique insight into the fission process. The presentation first discusses the present status of FREYA, which has now been extended up to energies where pre-equilibrium emission becomes significant and one or more neutrons may be emitted prior to fission. Concentrating on {sup 239}Pu(n,f), we discuss the neutron multiplicity correlations, the dependence of the neutron energy spectrum on the neutron multiplicity, and the relationship between the fragment kinetic energy and the number of neutrons and their energies. We also briefly suggest novel fission observables that could be measured with modern detectors.

  7. Manganese superoxide dismutase (Sod2) and redox-control of signaling events that drive metastasis

    PubMed Central

    Hempel, Nadine; Carrico, Pauline M.; Melendez, J. Andres

    2013-01-01

    Manganese superoxide dismutase (Sod2) has emerged as a key enzyme with a dual role in tumorigenic progression. Early studies were primarily directed at defining the tumor suppressive function of Sod2 based on its low level expression in many tumor types. It is now commonly held that loss of Sod2 expression is likely an early event in tumor progression allowing for further propagation of the tumorigenic phenotype resulting from steady state increases in free radical production. Increases in free radical load have also been linked to defects in mitochondrial function and metastatic disease progression. It was initially believed that Sod2 loss may propagate metastatic disease progression, in reality both epidemiologic and experimental evidence indicate that Sod2 levels increase in many tumor types as they progress from early stage non-invasive disease to late stage metastatic disease. Sod2 overexpression in many instances enhances the metastatic phenotype that is reversed by efficient H2O2 scavenging. This review evaluates the many sequelae associated with increases in Sod2 that impinge on the metastatic phenotype. The ability to use Sod2 to modulate the cellular redox-environment has allowed for the identification of redox-responsive signaling events that drive malignancy, such as invasion, migration and prolonged tumor cell survival. Further studies of these redox-driven events will help in the development of targeted therapeutic strategies to efficiently restrict redox-signaling essential for malignant progression. PMID:21434856

  8. Asplatin enhances drug efficacy by altering the cellular response.

    PubMed

    Cheng, Qinqin; Shi, Hongdong; Wang, Hongxia; Wang, Jun; Liu, Yangzhong

    2016-07-13

    Aspirin, a widely used anti-inflammatory drug, has been shown to be effective for the prevention and remission of cancers (Science, 2012, 337(21) 1471-1473). Asplatin, a Pt(iv) prodrug of cisplatin with the ligation of aspirin (c,c,t-[PtCl2(NH3)2(OH)(aspirin)]), demonstrates significantly higher cytotoxicity than cisplatin towards tumor cells and almost fully overcomes the drug resistance of cisplatin resistant cells. In this work, we have studied the molecular mechanism of asplatin by investigating the cellular response to this compound in order to understand the prominent inhibitory effect on the proliferation of cancer cells. The apoptosis analyses and the related gene expression measurements show that aspirin released from asplatin significantly modulates the cellular response to the platinum agent. Asplatin promotes the apoptosis via the BCL-2 associated mitochondrial pathway. The down-regulation of BCL-2 along with the up-regulation of BAX and BAK enhances the mitochondrial outer membrane permeability, resulting in the cytochrome c release from mitochondria into the cytosol. This event promotes the apoptosis by activation of caspase processing. Consequently, the ligation of aspirin significantly enhances the drug efficacy of the platinum complex in the low micromolar range. The alteration of the cellular response is probably responsible for the circumvention of the cisplatin resistance by asplatin. These results provide an insight into the mechanism of asplatin and provide information for designing new classic platinum drugs. PMID:27125788

  9. Features, Events, and Processes: Disruptive Events

    SciTech Connect

    P. Sanchez

    2004-11-08

    The purpose of this analysis report is to evaluate and document the inclusion or exclusion of the disruptive events features, events, and processes (FEPs) with respect to modeling used to support the total system performance assessment for license application (TSPA-LA). A screening decision, either ''Included'' or ''Excluded,'' is given for each FEP, along with the technical basis for screening decisions. This information is required by the U.S. Nuclear Regulatory Commission (NRC) at 10 CFR 63.114 (d), (e), and (f) [DIRS 156605]. The FEPs addressed in this report deal with both seismic and igneous disruptive events, such as fault displacements through the repository and an igneous intrusion into the repository. For included FEPs, this analysis summarizes the implementation of the FEP in TSPA-LA (i.e., how the FEP is included). For excluded FEPs, this analysis provides the technical basis for exclusion from TSPA-LA (i.e., why the FEP is excluded). Previous versions of this report were developed to support the total system performance assessments (TSPA) for various prior repository designs. This revision addresses the repository design for the license application (LA).

  10. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  11. Events and Constructs

    ERIC Educational Resources Information Center

    Smith, Noel W.

    2007-01-01

    Psychology has largely ignored the distinction between constructs and events and what comprises a scientific construct, yet this distinction is basic to some of the major divisions of thought within the discipline. Several kinds of constructs are identified and compared with events, and improper use of constructs is noted of which the mind…

  12. Committed Sport Event Volunteers

    ERIC Educational Resources Information Center

    Han, Keunsu; Quarterman, Jerome; Strigas, Ethan; Ha, Jaehyun; Lee, Seungbum

    2013-01-01

    The purpose of this study was to investigate the relationships among selected demographic characteristics (income, education and age), motivation and commitment of volunteers at a sporting event. Three-hundred and five questionnaires were collected from volunteers in a marathon event and analyzed using structural equation modeling (SEM). Based on…

  13. Event generator overview

    SciTech Connect

    Pang, Y.

    1997-12-01

    Due to their ability to provide detailed and quantitative predictions, the event generators have become an important part of studying relativistic heavy ion physics and of designing future experiments. In this talk, the author will briefly summarize recent progress in developing event generators for the relativistic heavy ion collisions.

  14. Cofunctional Subpathways Were Regulated by Transcription Factor with Common Motif, Common Family, or Common Tissue

    PubMed Central

    Su, Fei; Shang, Desi; Xu, Yanjun; Feng, Li; Yang, Haixiu; Liu, Baoquan; Su, Shengyang; Chen, Lina; Li, Xia

    2015-01-01

    Dissecting the characteristics of the transcription factor (TF) regulatory subpathway is helpful for understanding the TF underlying regulatory function in complex biological systems. To gain insight into the influence of TFs on their regulatory subpathways, we constructed a global TF-subpathways network (TSN) to analyze systematically the regulatory effect of common-motif, common-family, or common-tissue TFs on subpathways. We performed cluster analysis to show that the common-motif, common-family, or common-tissue TFs that regulated the same pathway classes tended to cluster together and contribute to the same biological function that led to disease initiation and progression. We analyzed the Jaccard coefficient to show that the functional consistency of subpathways regulated by the TF pairs with common motif, common family, or common tissue was significantly greater than the random TF pairs at the subpathway level, pathway level, and pathway class level. For example, HNF4A (hepatocyte nuclear factor 4, alpha) and NR1I3 (nuclear receptor subfamily 1, group I, member 3) were a pair of TFs with common motif, common family, and common tissue. They were involved in drug metabolism pathways and were liver-specific factors required for physiological transcription. In short, we inferred that the cofunctional subpathways were regulated by common-motif, common-family, or common-tissue TFs. PMID:26688819

  15. Maize Prolamins Could Induce a Gluten-Like Cellular Immune Response in Some Celiac Disease Patients

    PubMed Central

    Ortiz-Sánchez, Juan P.; Cabrera-Chávez, Francisco; Calderón de la Barca, Ana M.

    2013-01-01

    Celiac disease (CD) is an autoimmune-mediated enteropathy triggered by dietary gluten in genetically prone individuals. The current treatment for CD is a strict lifelong gluten-free diet. However, in some CD patients following a strict gluten-free diet, the symptoms do not remit. These cases may be refractory CD or due to gluten contamination; however, the lack of response could be related to other dietary ingredients, such as maize, which is one of the most common alternatives to wheat used in the gluten-free diet. In some CD patients, as a rare event, peptides from maize prolamins could induce a celiac-like immune response by similar or alternative pathogenic mechanisms to those used by wheat gluten peptides. This is supported by several shared features between wheat and maize prolamins and by some experimental results. Given that gluten peptides induce an immune response of the intestinal mucosa both in vivo and in vitro, peptides from maize prolamins could also be tested to determine whether they also induce a cellular immune response. Hypothetically, maize prolamins could be harmful for a very limited subgroup of CD patients, especially those that are non-responsive, and if it is confirmed, they should follow, in addition to a gluten-free, a maize-free diet. PMID:24152750

  16. Origin of giant viruses from smaller DNA viruses not from a fourth domain of cellular life

    PubMed Central

    Yutin, Natalya; Wolf, Yuri I.; Koonin, Eugene V.

    2015-01-01

    The numerous and diverse eukaryotic viruses with large double-stranded DNA genomes that at least partially reproduce in the cytoplasm of infected cells apparently evolved from a single virus ancestor. This major group of viruses is known as Nucleocytoplasmic Large DNA Viruses (NCLDV) or the proposed order Megavirales. Among the “Megavirales”, there are three groups of giant viruses with genomes exceeding 500 kb, namely Mimiviruses, Pithoviruses, and Pandoraviruses that hold the current record of viral genome size, about 2.5 Mb. Phylogenetic analysis of conserved, ancestral NLCDV genes clearly shows that these three groups of giant viruses have three distinct origins within the “Megavirales”. The Mimiviruses constitute a distinct family that is distantly related to Phycodnaviridae, Pandoraviruses originate from a common ancestor with Coccolithoviruses within the Phycodnaviridae family, and Pithoviruses are related to Iridoviridae and Marseilleviridae. Maximum likelihood reconstruction of gene gain and loss events during the evolution of the “Megavirales” indicates that each group of giant viruses evolved from viruses with substantially smaller and simpler gene repertoires. Initial phylogenetic analysis of universal genes, such as translation system components, encoded by some giant viruses, in particular Mimiviruses, has led to the hypothesis that giant viruses descend from a fourth, probably extinct domain of cellular life. The results of our comprehensive phylogenomic analysis of giant viruses refute the fourth domain hypothesis and instead indicate that the universal genes have been independently acquired by different giant viruses from their eukaryotic hosts. PMID:25042053

  17. The potential of cellular network infrastructures for sudden rainfall monitoring in dry climate regions

    NASA Astrophysics Data System (ADS)

    David, N.; Alpert, P.; Messer, H.

    2013-09-01

    Monitoring of precipitation and in particular sudden rain, in rural dry climate regions, is a subject of great significance in several weather related processes such as soil erosion, flash flooding, triggering epidemics and more. The rainfall monitoring facilities in these regions and as a result precipitation data are, however, commonly, severely lacking. As was recently shown, cellular networks infrastructures supply high resolution precipitation measurements at ground level while often being situated in dry areas, covering large parts of these climatic zones. The potential found in these systems to provide early monitoring and essential precipitation information, directly from arid regions, based on standard measurements of commercial microwave links, is exemplified here over the Negev and the Southern Judean desert, South Israel. We present the results of two different rainfall events occurred in these regions. It is shown that the microwave system measured precipitation between at least 50 min (in case 1) and at least 1 h and 40 min (in case 2) before each of the sparse rain gauges. During each case, the radar system, located relatively far from the arid sites, provided measurements from heights of at least 1500 m and 2000 m above surface, respectively. A third case study demonstrates a relative advantage of microwave links to measure precipitation intensity with respect to the radar system, over an area of complex topography located in northeastern Israel, which is relatively far (~ 150 km) from the radar.

  18. Contrasting Large Solar Events

    NASA Astrophysics Data System (ADS)

    Lanzerotti, Louis J.

    2010-10-01

    After an unusually long solar minimum, solar cycle 24 is slowly beginning. A large coronal mass ejection (CME) from sunspot 1092 occurred on 1 August 2010, with effects reaching Earth on 3 August and 4 August, nearly 38 years to the day after the huge solar event of 4 August 1972. The prior event, which those of us engaged in space research at the time remember well, recorded some of the highest intensities of solar particles and rapid changes of the geomagnetic field measured to date. What can we learn from the comparisons of these two events, other than their essentially coincident dates? One lesson I took away from reading press coverage and Web reports of the August 2010 event is that the scientific community and the press are much more aware than they were nearly 4 decades ago that solar events can wreak havoc on space-based technologies.

  19. Whole-Organism Cellular Pathology: A Systems Approach to Phenomics.

    PubMed

    Cheng, K C; Katz, S R; Lin, A Y; Xin, X; Ding, Y

    2016-01-01

    Phenotype is defined as the state of an organism resulting from interactions between genes, environment, disease, molecular mechanisms, and chance. The purpose of the emerging field of phenomics is to systematically determine and measure phenotypes across biology for the sake of understanding. Phenotypes can affect more than one cell type and life stage, so ideal phenotyping would include the state of every cell type within the context of both tissue architecture and the whole organism at each life stage. In medicine, high-resolution anatomic assessment of phenotype is obtained from histology. Histology's interpretative power, codified by Virchow as cellular pathology, is derived from its ability to discern diagnostic and characteristic cellular changes in diseased tissues. Cellular pathology is observed in every major human disease and relies on the ability of histology to detect cellular change in any cell type due to unbiased pan-cellular staining, even in optically opaque tissues. Our laboratory has shown that histology is far more sensitive than stereomicroscopy for detecting phenotypes in zebrafish mutants. Those studies have also shown that more complete sampling, greater consistency in sample orientation, and the inclusion of phenotypes extending over longer length scales would provide greater coverage of common phenotypes. We are developing technical approaches to achieve an ideal detection of cellular pathology using an improved form of X-ray microtomography that retains the strengths and addresses the weaknesses of histology as a screening tool. We are using zebrafish as a vertebrate model based on the overlaps between zebrafish and mammalian tissue architecture, and a body size small enough to allow whole-organism, volumetric imaging at cellular resolution. Automation of whole-organism phenotyping would greatly increase the value of phenomics. Potential societal benefits would include reduction in the cost of drug development, a reduction in the

  20. Hyaluronan-mediated cellular adhesion

    NASA Astrophysics Data System (ADS)

    Curtis, Jennifer

    2005-03-01

    Many cells surround themselves with a cushioning halo of polysaccharides that is further strengthened and organized by proteins. In fibroblasts and chrondrocytes, the primary component of this pericellular matrix is hyaluronan, a large linear polyanion. Hyaluronan production is linked to a variety of disease, developmental, and physiological processes. Cells manipulate the concentration of hyaluronan and hyaluronan receptors for numerous activities including modulation of cell adhesion, cell motility, and differentiation. Recent investigations by identify hyaluronan's role in mediating early-stage cell adhesion. An open question is how the cell removes the 0.5-10 micron thick pericellular matrix to allow for further mature adhesion events requiring nanometer scale separations. In this investigation, holographic optical tweezers are used to study the adhesion and viscoelastic properties of chondrocytes' pericellular matrix. Ultimately, we aim to shed further light on the spatial and temporal details of the dramatic transition from micron to nanometer gaps between the cell and its adhesive substrate.

  1. Integrated segmentation of cellular structures

    NASA Astrophysics Data System (ADS)

    Ajemba, Peter; Al-Kofahi, Yousef; Scott, Richard; Donovan, Michael; Fernandez, Gerardo

    2011-03-01

    Automatic segmentation of cellular structures is an essential step in image cytology and histology. Despite substantial progress, better automation and improvements in accuracy and adaptability to novel applications are needed. In applications utilizing multi-channel immuno-fluorescence images, challenges include misclassification of epithelial and stromal nuclei, irregular nuclei and cytoplasm boundaries, and over and under-segmentation of clustered nuclei. Variations in image acquisition conditions and artifacts from nuclei and cytoplasm images often confound existing algorithms in practice. In this paper, we present a robust and accurate algorithm for jointly segmenting cell nuclei and cytoplasm using a combination of ideas to reduce the aforementioned problems. First, an adaptive process that includes top-hat filtering, Eigenvalues-of-Hessian blob detection and distance transforms is used to estimate the inverse illumination field and correct for intensity non-uniformity in the nuclei channel. Next, a minimum-error-thresholding based binarization process and seed-detection combining Laplacian-of-Gaussian filtering constrained by a distance-map-based scale selection is used to identify candidate seeds for nuclei segmentation. The initial segmentation using a local maximum clustering algorithm is refined using a minimum-error-thresholding technique. Final refinements include an artifact removal process specifically targeted at lumens and other problematic structures and a systemic decision process to reclassify nuclei objects near the cytoplasm boundary as epithelial or stromal. Segmentation results were evaluated using 48 realistic phantom images with known ground-truth. The overall segmentation accuracy exceeds 94%. The algorithm was further tested on 981 images of actual prostate cancer tissue. The artifact removal process worked in 90% of cases. The algorithm has now been deployed in a high-volume histology analysis application.

  2. Cellular toxicity of nicotinamide metabolites.

    PubMed

    Rutkowski, Bolesław; Rutkowski, Przemysław; Słomińska, Ewa; Smolenski, Ryszard T; Swierczyński, Julian

    2012-01-01

    There are almost 100 different substances called uremic toxins. Nicotinamide derivatives are known as new family of uremic toxins. These uremic compounds play a role in an increased oxidative stress and disturbances in cellular repair processes by inhibiting poly (ADP-ribose) polymerase activity. New members of this family were discovered and described. Their toxic properties were a subject of recent studies. This study evaluated the concentration of 4-pyridone-3-carboxamid-1-β-ribonucleoside-triphosphate (4PYTP) and 4-pyridone-3-carboxamid-1-β-ribonucleoside-monophosphate (4PYMP) in erythrocytes of patients with chronic renal failure. Serum and red blood cells were collected from chronic renal failure patients on conservative treatment, those treated with hemodialysis, and at different times from those who underwent kidney transplantation. Healthy volunteers served as a control group. Nicotinamide metabolites were determined using liquid chromatography with mass spectrometry based on originally discovered and described method. Three novel compounds were described: 4-pyridone-3-carboxamid-1-β-ribonucleoside (4PYR), 4PYMP, and 4PYTP. 4PYR concentration was elevated in the serum, whereas 4PYMP and 4PYTP concentrations were augmented in erythrocytes of dialysis patients. Interestingly, concentrations of these compounds were less elevated during the treatment with erythropoietin-stimulating agents (ESAs). After successful kidney transplantation, concentrations of 4PYR and 4PYMP normalized according to the graft function, whereas that of 4PYTP was still elevated. During the incubation of erythrocytes in the presence of 4PYR, concentration of 4PYMP rose very rapidly while that of 4PYTP increased slowly. Therefore, we hypothesized that 4PYR, as a toxic compound, was actively absorbed by erythrocytes and metabolized to the 4PYMP and 4PYTP, which may interfere with function and life span of these cells. PMID:22200423

  3. Electrodynamic eigenmodes in cellular morphology.

    PubMed

    Cifra, M

    2012-09-01

    Eigenmodes of the spherical and ellipsoidal dielectric electromagnetic resonator have been analysed. The sizes and shape of the resonators have been chosen to represent the shape of the interphase and dividing animal cell. Electromagnetic modes that have shape exactly suitable for positioning of the sufficiently large organelles in cell (centrosome, nucleus) have been identified. We analysed direction and magnitude of dielectrophoretic force exerted on large organelles by electric field of the modes. We found that the TM(1m1) mode in spherical resonator acts by centripetal force which drags the large organelles which have higher permittivity than the cytosol to the center of the cell. TM-kind of mode in the ellipsoidal resonator acts by force on large polarizable organelles in a direction that corresponds to the movement of the centrosomes (also nucleus) observed during the cell division, i.e. to the foci of the ellipsoidal cell. Minimal required force (10(-16) N), gradient of squared electric field and corresponding energy (10(-16) J) of the mode have been calculated to have biological significance within the periods on the order of time required for cell division. Minimal required energy of the mode, in order to have biological significance, can be lower in the case of resonance of organelle with the field of the cellular resonator mode. In case of sufficient energy in the biologically relevant mode, electromagnetic field of the mode will act as a positioning or steering mechanism for centrosome and nucleus in the cell, thus contribute to the spatial and dynamical self-organization in biological systems. PMID:22750075

  4. Cellular Manufacturing Internet Performance Support System

    SciTech Connect

    Bohley, M.C.; Schwartz, M.E.

    1998-03-04

    The objective of this project was to develop an Internet-based electronic performance support system (EPSS) for cellular manufacturing providing hardware/software specifications, process descriptions, estimated cost savings, manufacturing simulations, training information, and service resources for government and industry users of Cincinnati Milacron machine tools and products. AlliedSignal Federal Manufacturing and Technologies (ASFM and T) used expertise in the areas of Internet design and multimedia creation to develop a performance support system (PSS) for the Internet with assistance from CM's subject matter experts from engineering, manufacturing, and technical support. Reference information was both created and re-purposed from other existing formats, then made available on the Internet. On-line references on cellular manufacturing operations include: definitions of cells and cellular manufacturing; illustrations on how cellular manufacturing improves part throughput, resource utilization, part quality, and manufacturing flexibility; illustrations on how cellular manufacturing reduces labor and overhead costs; identification of critical factors driving decisions toward cellular manufacturing; a method for identifying process improvement areas using cellular manufacturing; a method for customizing the size of cells for a specific site; a simulation for making a part using cellular manufacturing technology; and a glossary of terms and concepts.

  5. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  6. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  7. 47 CFR 22.909 - Cellular markets.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Metropolitan Areas and the Gulf of Mexico Service Area (water area of the Gulf of Mexico, border is the coastline), defined by the Office of Management and Budget, as modified by the FCC. (b) RSAs. Rural Service... used by the FCC for administrative convenience in the licensing of cellular systems. Cellular...

  8. From Cnn Dynamics to Cellular Wave Computers

    NASA Astrophysics Data System (ADS)

    Roska, Tamas

    2013-01-01

    Embedded in a historical overview, the development of the Cellular Wave Computing paradigm is presented, starting from the standard CNN dynamics. The theoretical aspects, the physical implementation, the innovation process, as well as the biological relevance are discussed in details. Finally, the latest developments, the physical versus virtual cellular machines, as well as some open questions are presented.

  9. 6 Common Cancers - Skin Cancer

    MedlinePlus

    ... Bar Home Current Issue Past Issues 6 Common Cancers - Skin Cancer Past Issues / Spring 2007 Table of Contents For ... AP Photo/Herald-Mail, Kevin G. Gilbert Skin Cancer Skin cancer is the most common form of ...

  10. Analyzing Commonality In A System

    NASA Technical Reports Server (NTRS)

    Pacheco, Alfred; Pool, Kevin

    1988-01-01

    Cost decreased by use of fewer types of parts. System Commonality Analysis Tool (SCAT) computer program designed to aid managers and engineers in identifying common, potentially common, and unique components of system. Incorporates three major functions: program for creation and maintenance of data base, analysis of commonality, and such system utilities as host-operating-system commands and loading and unloading of data base. Produces reports tabulating maintenance, initial configurations, and expected total costs. Written in FORTRAN 77.

  11. Cellular reprogramming through mitogen-activated protein kinases

    PubMed Central

    Lee, Justin; Eschen-Lippold, Lennart; Lassowskat, Ines; Böttcher, Christoph; Scheel, Dierk

    2015-01-01

    Mitogen-activated protein kinase (MAPK) cascades are conserved eukaryote signaling modules where MAPKs, as the final kinases in the cascade, phosphorylate protein substrates to regulate cellular processes. While some progress in the identification of MAPK substrates has been made in plants, the knowledge on the spectrum of substrates and their mechanistic action is still fragmentary. In this focused review, we discuss the biological implications of the data in our original paper (Sustained mitogen-activated protein kinase activation reprograms defense metabolism and phosphoprotein profile in Arabidopsis thaliana; Frontiers in Plant Science 5: 554) in the context of related research. In our work, we mimicked in vivo activation of two stress-activated MAPKs, MPK3 and MPK6, through transgenic manipulation of Arabidopsis thaliana and used phosphoproteomics analysis to identify potential novel MAPK substrates. Here, we plotted the identified putative MAPK substrates (and downstream phosphoproteins) as a global protein clustering network. Based on a highly stringent selection confidence level, the core networks highlighted a MAPK-induced cellular reprogramming at multiple levels of gene and protein expression—including transcriptional, post-transcriptional, translational, post-translational (such as protein modification, folding, and degradation) steps, and also protein re-compartmentalization. Additionally, the increase in putative substrates/phosphoproteins of energy metabolism and various secondary metabolite biosynthesis pathways coincides with the observed accumulation of defense antimicrobial substances as detected by metabolome analysis. Furthermore, detection of protein networks in phospholipid or redox elements suggests activation of downstream signaling events. Taken in context with other studies, MAPKs are key regulators that reprogram cellular events to orchestrate defense signaling in eukaryotes. PMID:26579181

  12. The cellular lipids of Romboutsia.

    PubMed

    Guan, Ziqiang; Chen, Lingli; Gerritsen, Jacoline; Smidt, Hauke; Goldfine, Howard

    2016-09-01

    We have examined the lipids of three isolates, Romboutsia lituseburensis, Romboutsia ilealis, and Romboutsia sp. strain FRIFI, of the newly described genus Romboutsia by two-dimensional thin-layer chromatography (2D-TLC) and by liquid chromatography/mass spectrometry (LC/MS). We have found three phospholipids, phosphatidylglycerol (PG), cardiolipin and phosphatidic acid in all three species. A fourth phospholipid, lysyl-PG, was found in R. lituseburensis and strain FRIFI. Polyprenyl-phosphates were identified in the lipid extracts of all three species. Three glycolipids, mono-, di- and tri-hexosyldiacylglycerol, were common to all three species. An additional glycolipid, tetrahexosyl-diacylglycerol was identified in strain FRIFI. Acylated trihexosyldiacylglycerol and acyl-tetrahexosydiacylglycerol were also found in R. ilealis and strain FRIFI. Remarkably, no alk-1-enyl ether lipids (plasmalogens) were present in Romboutsia as distinct from bacteria of the related genus Clostridium in which these ether lipids are common. We have compared the lipidome of Romboutsia with that recently described for Clostridium difficile, which has plasmalogens, no lysyl-PG, and no tetrahexosyl-diacylglycerol. According to 16S rRNA gene sequencing, Romboutsia spp. and C. difficile are closely related (>95% sequence identity). PMID:27317428

  13. Culture and the Common School

    ERIC Educational Resources Information Center

    Feinberg, Walter

    2007-01-01

    This essay addresses the question: given the flattening out of the cultural hierarchy that was the vestige of colonialism and nation-building, is there anything that might be uniquely common about the common school in this postmodern age? By "uniquely common" I do not mean those subjects that all schools might teach, such as reading or arithmetic.…

  14. Committee Handbook for Common Learning.

    ERIC Educational Resources Information Center

    Burton, Sharon; And Others

    This manual on general education and common learning was prepared by and for the Dallas County Community College District's (DCCCD's) Committees for Common Learning (CCL's), which have been charged with reviewing the DCCCD's general education curriculum and degree requirements and making recommendations concerning common learning requirements and…

  15. Common Core State Standards 101

    ERIC Educational Resources Information Center

    Rothman, Robert

    2013-01-01

    The Common Core State Standards (CCSS) represent the first time that nearly every state has set common expectations for what students should know and be able to do. In the past, each state set its own standards, and the results varied widely. And while states collectively developed these common standards, decisions about the curriculum and…

  16. Developing Cellular Therapies for Retinal Degenerative Diseases

    PubMed Central

    Bharti, Kapil; Rao, Mahendra; Hull, Sara Chandros; Stroncek, David; Brooks, Brian P.; Feigal, Ellen; van Meurs, Jan C.; Huang, Christene A.; Miller, Sheldon S.

    2014-01-01

    Biomedical advances in vision research have been greatly facilitated by the clinical accessibility of the visual system, its ease of experimental manipulation, and its ability to be functionally monitored in real time with noninvasive imaging techniques at the level of single cells and with quantitative end-point measures. A recent example is the development of stem cell–based therapies for degenerative eye diseases including AMD. Two phase I clinical trials using embryonic stem cell–derived RPE are already underway and several others using both pluripotent and multipotent adult stem cells are in earlier stages of development. These clinical trials will use a variety of cell types, including embryonic or induced pluripotent stem cell–derived RPE, bone marrow– or umbilical cord–derived mesenchymal stem cells, fetal neural or retinal progenitor cells, and adult RPE stem cells–derived RPE. Although quite distinct, these approaches, share common principles, concerns and issues across the clinical development pipeline. These considerations were a central part of the discussions at a recent National Eye Institute meeting on the development of cellular therapies for retinal degenerative disease. At this meeting, emphasis was placed on the general value of identifying and sharing information in the so-called “precompetitive space.” The utility of this behavior was described in terms of how it could allow us to remove road blocks in the clinical development pipeline, and more efficiently and economically move stem cell–based therapies for retinal degenerative diseases toward the clinic. Many of the ocular stem cell approaches we discuss are also being used more broadly, for nonocular conditions and therefore the model we develop here, using the precompetitive space, should benefit the entire scientific community. PMID:24573369

  17. Raft lipids as common components of human extracellular amyloid fibrils

    PubMed Central

    Gellermann, Gerald P.; Appel, Thomas R.; Tannert, Astrid; Radestock, Anja; Hortschansky, Peter; Schroeckh, Volker; Leisner, Christian; Lütkepohl, Tim; Shtrasburg, Shmuel; Röcken, Christoph; Pras, Mordechai; Linke, Reinhold P.; Diekmann, Stephan; Fändrich, Marcus

    2005-01-01

    Amyloid fibrils are fibrillar polypeptide aggregates from several degenerative human conditions, including Alzheimer's and Creutzfeldt-Jakob diseases. Analysis of amyloid fibrils derived from various human diseases (AA, ATTR, Aβ2M, ALλ, and ALκ amyloidosis) shows that these are associated with a common lipid component that has a conserved chemical composition and that is specifically rich in cholesterol and sphingolipids, the major components of cellular lipid rafts. This pattern is not notably affected by the purification procedure, and no tight lipid interactions can be detected when preformed fibrils are mixed with lipids. By contrast, the early and prefibrillar aggregates formed in an AA amyloid-producing cell system interact with the raft marker ganglioside-1, and amyloid formation is impaired by addition of cholesterol-reducing agents. These data suggest the existence of common cellular mechanisms in the generation of different types of clinical amyloid deposits. PMID:15851687

  18. Cellular metabolism and disease: what do metabolic outliers teach us?

    PubMed Central

    DeBerardinis, Ralph J.; Thompson, Craig B.

    2012-01-01

    An understanding of metabolic pathways based solely on biochemistry textbooks would underestimate the pervasive role of metabolism in essentially every aspect of biology. It is evident from recent work that many human diseases involve abnormal metabolic states – often genetically programmed – that perturb normal physiology and lead to severe tissue dysfunction. Understanding these metabolic outliers is now a crucial frontier in disease-oriented research. This review discusses the broad impact of metabolism in cellular function, how modern concepts of metabolism can inform our understanding of common diseases like cancer, and considers the prospects of developing new metabolic approaches to disease treatment. PMID:22424225

  19. Cellular Organization of Neuroimmune Interactions in the Gastrointestinal Tract

    PubMed Central

    Margolis, Kara Gross; Gershon, Michael David; Bogunovic, Milena

    2016-01-01

    The gastrointestinal (GI) tract is the largest immune organ; in vertebrates, it is the only organ whose function is controlled by its own intrinsic enteric nervous system (ENS), but it is additionally regulated by extrinsic (sympathetic and parasympathetic) innervation. The GI nervous and immune systems are highly integrated in their common goal, which is to unite digestive functions with protection from ingested environmental threats. This review discusses the physiological relevance of enteric neuroimmune integration by summarizing the current knowledge of evolutionary and developmental pathways, cellular organization, and molecular mechanisms of neuroimmune interactions in health and disease. PMID:27289177

  20. Cellular localization of gonadotropin-releasing hormone (GnRH) I and GnRH II in first-trimester human placenta and decidua.

    PubMed

    Chou, Chun-Shan; Beristain, Alexander G; MacCalman, Colin D; Leung, Peter C K

    2004-03-01

    There is increasing evidence to suggest that the classical form of GnRH (GnRH I) and the second mammalian form of this hormone, GnRH II, play regulatory roles in human implantation and placentation. To date, the cellular distribution of these two hormones at the maternal-fetal interface remains poorly characterized. In these studies, we localized GnRH I and GnRH II expression in human placenta and decidua to distinct subpopulations of cells isolated from these tissues and in a chorionic villous/decidual tissue coculture system that mimics many of the cellular events of early placentation. GnRH I and GnRH II mRNA transcripts were detected in first-trimester placenta, whereas only GnRH I was detected in tissues obtained at term. Both hormones were further immunolocalized to the mononucleate villous and distinct subpopulations of extravillous cytotrophoblasts of the placenta in vivo and in vitro. In contrast, GnRH I but not GnRH II was expressed in the outer multinucleated syncytial trophoblast layer of first trimester chorionic villi and in cultures of villous cytotrophoblasts allowed to undergo differentiation and fusion in vitro. GnRH I and GnRH II were also found to be coexpressed in first-trimester decidua and primary cultures of decidual stromal cells. Collectively, these observations demonstrate that GnRH I and GnRH II have both common and discrete cellular distributions in the placenta and decidua and suggest that these two hormones are capable of eliciting their biological actions in an autocrine and/or paracrine manner within and between these maternal and fetal cellular compartments. PMID:15001648

  1. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence

    PubMed Central

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  2. Markers of cellular senescence. Telomere shortening as a marker of cellular senescence.

    PubMed

    Bernadotte, Alexandra; Mikhelson, Victor M; Spivak, Irina M

    2016-01-01

    The cellular senescence definition comes to the fact of cells irreversible proliferation disability. Besides the cell cycle arrest, senescent cells go through some morphological, biochemical, and functional changes which are the signs of cellular senescence. The senescent cells (including replicative senescence and stress-induced premature senescence) of all the tissues look alike. They are metabolically active and possess the set of characteristics in vitro and in vivo, which are known as biomarkers of aging and cellular senescence. Among biomarkers of cellular senescence telomere shortening is a rather elegant frequently used biomarker. Validity of telomere shortening as a marker for cellular senescence is based on theoretical and experimental data. PMID:26805432

  3. FLOOD EVENT MAPPING IMAGES

    EPA Science Inventory

    OSEI flood products (FLD) include multichannel color composite imagery and single-channel grayscale imagery of enlarged river areas or increased sediment flow. Typically, these events are displayed by comparison to imagery taken when flooding was not occurring.

  4. Holter and Event Monitors

    MedlinePlus

    ... Holter and event monitors are similar to an EKG (electrocardiogram). An EKG is a simple test that detects and records ... for diagnosing heart rhythm problems. However, a standard EKG only records the heartbeat for a few seconds. ...

  5. Event shape sorting

    NASA Astrophysics Data System (ADS)

    Kopečná, Renata; Tomášik, Boris

    2016-04-01

    We propose a novel method for sorting events of multiparticle production according to the azimuthal anisotropy of their momentum distribution. Although the method is quite general, we advocate its use in analysis of ultra-relativistic heavy-ion collisions where a large number of hadrons is produced. The advantage of our method is that it can automatically sort out samples of events with histograms that indicate similar distributions of hadrons. It takes into account the whole measured histograms with all orders of anisotropy instead of a specific observable ( e.g., v_2 , v_3 , q_2 . It can be used for more exclusive experimental studies of flow anisotropies which are then more easily compared to theoretical calculations. It may also be useful in the construction of mixed-events background for correlation studies as it allows to select events with similar momentum distribution.

  6. "Universe" event at AIMS

    NASA Astrophysics Data System (ADS)

    2008-06-01

    Report of event of 11 May 2008 held at the African Institute of Mathematical Sciences (Muizenberg, Cape), with speakers Michael Griffin (Administrator of NASA), Stephen Hawking (Cambridge), David Gross (Kavli Institute, Santa Barbara) and George Smoot (Berkeley).

  7. Leading the Common Core State Standards: From Common Sense to Common Practice

    ERIC Educational Resources Information Center

    Dunkle, Cheryl A.

    2012-01-01

    Many educators agree that we already know how to foster student success, so what is keeping common sense from becoming common practice? The author provides step-by-step guidance for overcoming the barriers to adopting the Common Core State Standards (CCSS) and achieving equity and excellence for all students. As an experienced teacher and…

  8. Auditory verbal hallucinations in schizophrenia and post-traumatic stress disorder: common phenomenology, common cause, common interventions?

    PubMed Central

    McCarthy-Jones, Simon; Longden, Eleanor

    2015-01-01

    Auditory verbal hallucinations (AVH: ‘hearing voices’) are found in both schizophrenia and post-traumatic stress disorder (PTSD). In this paper we first demonstrate that AVH in these two diagnoses share a qualitatively similar phenomenology. We then show that the presence of AVH in schizophrenia is often associated with earlier exposure to traumatic/emotionally overwhelming events, as it is by definition in PTSD. We next argue that the content of AVH relates to earlier traumatic events in a similar way in both PTSD and schizophrenia, most commonly having direct or indirect thematic links to emotionally overwhelming events, rather than being direct re-experiencing. We then propose, following cognitive models of PTSD, that the reconstructive nature of memory may be able to account for the nature of these associations between trauma and AVH content, as may threat-hypervigilance and the individual’s personal goals. We conclude that a notable subset of people diagnosed with schizophrenia with AVH are having phenomenologically and aetiologically identical experiences to PTSD patients who hear voices. As such we propose that the iron curtain between AVH in PTSD (often termed ‘dissociative AVH’) and AVH in schizophrenia (so-called ‘psychotic AVH’) needs to be torn down, as these are often the same experience. One implication of this is that these trauma-related AVH require a common trans-diagnostic treatment strategy. Whilst antipsychotics are already increasingly being used to treat AVH in PTSD, we argue for the centrality of trauma-based interventions for trauma-based AVH in both PTSD and in people diagnosed with schizophrenia. PMID:26283997

  9. Statistical Mechanics of Surjective Cellular Automata

    NASA Astrophysics Data System (ADS)

    Kari, Jarkko; Taati, Siamak

    2015-09-01

    Reversible cellular automata are seen as microscopic physical models, and their states of macroscopic equilibrium are described using invariant probability measures. We establish a connection between the invariance of Gibbs measures and the conservation of additive quantities in surjective cellular automata. Namely, we show that the simplex of shift-invariant Gibbs measures associated to a Hamiltonian is invariant under a surjective cellular automaton if and only if the cellular automaton conserves the Hamiltonian. A special case is the (well-known) invariance of the uniform Bernoulli measure under surjective cellular automata, which corresponds to the conservation of the trivial Hamiltonian. As an application, we obtain results indicating the lack of (non-trivial) Gibbs or Markov invariant measures for "sufficiently chaotic" cellular automata. We discuss the relevance of the randomization property of algebraic cellular automata to the problem of approach to macroscopic equilibrium, and pose several open questions. As an aside, a shift-invariant pre-image of a Gibbs measure under a pre-injective factor map between shifts of finite type turns out to be always a Gibbs measure. We provide a sufficient condition under which the image of a Gibbs measure under a pre-injective factor map is not a Gibbs measure. We point out a potential application of pre-injective factor maps as a tool in the study of phase transitions in statistical mechanical models.

  10. Cellular telephones and non-Hodgkin lymphoma.

    PubMed

    Linet, Martha S; Taggart, Theresa; Severson, Richard K; Cerhan, James R; Cozen, Wendy; Hartge, Patricia; Colt, Joanne

    2006-11-15

    Dramatic increase in hand-held cellular telephone use since the 1980s and excess risk of lymphoproliferative malignancies associated with radio-frequency radiation (RFR) exposures in epidemiological and experimental studies motivated assessment of cellular telephones within a comprehensive US case-control investigation of non-Hodgkin lymphoma (NHL). A questionnaire ascertained cellular telephone use in 551 NHL cases and 462 frequency-matched population controls. Compared to persons who had never used cellular telephones, risks were not increased among individuals whose lifetime use was fewer than 10 (odds ratio (OR) = 0.9, 95% confidence intervals (CI): 0.6, 1.3), 10-100 (OR = 1.0, 95 % CI: 0.7, 1.5) or more than 100 times (e.g., regular users, OR = 0.9, 95% CI: 0.6, 1.4). Among regular users compared to those who had never used hand-held cellular telephones, risks of NHL were not significantly associated with minutes per week, duration, cumulative lifetime or year of first use, although NHL was non-significantly higher in men who used cellular telephones for more than 8 years. Little evidence linked use of cellular telephones with total, diffuse large B-cell lymphoma or follicular NHL. These findings must be interpreted in the context of less than 5% of the population reporting duration of use of 6 or more years or lifetime cumulative use of 200 or more hours. PMID:16894556

  11. CHED Events: New Orleans

    NASA Astrophysics Data System (ADS)

    Wink, Donald J.

    2008-03-01

    These Division of Chemical Education (CHED) Committee meetings and events are planned for the Spring 2008 ACS Meeting in New Orleans. Most will take place in the Hilton Riverside Hotel, 2 Poydras Street; this includes the Sunday evening Reception and Social Event; there will be no CHED Banquet. Exceptions are the Sunday evening Poster Session and the Undergraduate Poster Sessions, which will be in Hall A of the Morial Convention Center.

  12. Spaces of Abstract Events

    NASA Astrophysics Data System (ADS)

    Chajda, Ivan; Länger, Helmut

    2013-06-01

    We generalize the concept of a space of numerical events in such a way that this generalization corresponds to arbitrary orthomodular posets whereas spaces of numerical events correspond to orthomodular posets having a full set of states. Moreover, we show that there is a natural one-to-one correspondence between orthomodular posets and certain posets with sectionally antitone involutions. Finally, we characterize orthomodular lattices among orthomodular posets.

  13. QCD (&) event generators

    SciTech Connect

    Skands, Peter Z.; /Fermilab

    2005-07-01

    Recent developments in QCD phenomenology have spurred on several improved approaches to Monte Carlo event generation, relative to the post-LEP state of the art. In this brief review, the emphasis is placed on approaches for (1) consistently merging fixed-order matrix element calculations with parton shower descriptions of QCD radiation, (2) improving the parton shower algorithms themselves, and (3) improving the description of the underlying event in hadron collisions.

  14. Quantitative Analysis of Cellular Metabolic Dissipative, Self-Organized Structures

    PubMed Central

    de la Fuente, Ildefonso Martínez

    2010-01-01

    One of the most important goals of the postgenomic era is understanding the metabolic dynamic processes and the functional structures generated by them. Extensive studies during the last three decades have shown that the dissipative self-organization of the functional enzymatic associations, the catalytic reactions produced during the metabolite channeling, the microcompartmentalization of these metabolic processes and the emergence of dissipative networks are the fundamental elements of the dynamical organization of cell metabolism. Here we present an overview of how mathematical models can be used to address the properties of dissipative metabolic structures at different organizational levels, both for individual enzymatic associations and for enzymatic networks. Recent analyses performed with dissipative metabolic networks have shown that unicellular organisms display a singular global enzymatic structure common to all living cellular organisms, which seems to be an intrinsic property of the functional metabolism as a whole. Mathematical models firmly based on experiments and their corresponding computational approaches are needed to fully grasp the molecular mechanisms of metabolic dynamical processes. They are necessary to enable the quantitative and qualitative analysis of the cellular catalytic reactions and also to help comprehend the conditions under which the structural dynamical phenomena and biological rhythms arise. Understanding the molecular mechanisms responsible for the metabolic dissipative structures is crucial for unraveling the dynamics of cellular life. PMID:20957111

  15. Composite alginate gels for tunable cellular microenvironment mechanics

    NASA Astrophysics Data System (ADS)

    Khavari, Adele; Nydén, Magnus; Weitz, David A.; Ehrlicher, Allen J.

    2016-08-01

    The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4–12 kPa) as compared to healthy tissue (E = 0.4–2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation.

  16. Axl as a mediator of cellular growth and survival

    PubMed Central

    Axelrod, Haley; Pienta, Kenneth J.

    2014-01-01

    The control of cellular growth and proliferation is key to the maintenance of homeostasis. Survival, proliferation, and arrest are regulated, in part, by Growth Arrest Specific 6 (Gas6) through binding to members of the TAM receptor tyrosine kinase family. Activation of the TAM receptors leads to downstream signaling through common kinases, but the exact mechanism within each cellular context varies and remains to be completely elucidated. Deregulation of the TAM family, due to its central role in mediating cellular proliferation, has been implicated in multiple diseases. Axl was cloned as the first TAM receptor in a search for genes involved in the progression of chronic to acute-phase leukemia, and has since been established as playing a critical role in the progression of cancer. The oncogenic nature of Axl is demonstrated through its activation of signaling pathways involved in proliferation, migration, inhibition of apoptosis, and therapeutic resistance. Despite its recent discovery, significant progress has been made in the development of effective clinical therapeutics targeting Axl. In order to accurately define the role of Axl in normal and diseased processes, it must be analyzed in a cell type-specific context. PMID:25344858

  17. Small-Molecule Inhibitors of SETD8 with Cellular Activity

    PubMed Central

    2015-01-01

    SETD8/SET8/Pr-SET7/KMT5A is the sole protein lysine methyltransferase (PKMT) known to monomethylate lysine 20 of histone H4 in vivo. SETD8’s methyltransferase activity has been implicated in many essential cellular processes including DNA replication, DNA damage response, transcription modulation, and cell cycle regulation. Developing SETD8 inhibitors with cellular activity is a key step toward elucidating the diverse roles of SETD8 via convenient pharmacological perturbation. From the hits of a prior high throughput screen (HTS), SPS8I1–3 (NSC663284, BVT948, and ryuvidine) were validated as potent SETD8 inhibitors. These compounds contain different structural motifs and inhibit SETD8 via distinct modes. More importantly, these compounds show cellular activity by suppressing the H4K20me1 mark of SETD8 and recapitulate characteristic S/G2/M-phase cell cycle defects as observed for RNAi-mediated SETD8 knockdown. The commonality of SPS8I1–3 against SETD8, together with their distinct structures and mechanisms for SETD8 inhibition, argues for the collective application of these compounds as SETD8 inhibitors. PMID:25137013

  18. Composite alginate gels for tunable cellular microenvironment mechanics.

    PubMed

    Khavari, Adele; Nydén, Magnus; Weitz, David A; Ehrlicher, Allen J

    2016-01-01

    The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4-12 kPa) as compared to healthy tissue (E = 0.4-2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation. PMID:27484403

  19. Interpreting BOLD: towards a dialogue between cognitive and cellular neuroscience.

    PubMed

    Hall, Catherine N; Howarth, Clare; Kurth-Nelson, Zebulun; Mishra, Anusha

    2016-10-01

    Cognitive neuroscience depends on the use of blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to probe brain function. Although commonly used as a surrogate measure of neuronal activity, BOLD signals actually reflect changes in brain blood oxygenation. Understanding the mechanisms linking neuronal activity to vascular perfusion is, therefore, critical in interpreting BOLD. Advances in cellular neuroscience demonstrating differences in this neurovascular relationship in different brain regions, conditions or pathologies are often not accounted for when interpreting BOLD. Meanwhile, within cognitive neuroscience, the increasing use of high magnetic field strengths and the development of model-based tasks and analyses have broadened the capability of BOLD signals to inform us about the underlying neuronal activity, but these methods are less well understood by cellular neuroscientists. In 2016, a Royal Society Theo Murphy Meeting brought scientists from the two communities together to discuss these issues. Here, we consolidate the main conclusions arising from that meeting. We discuss areas of consensus about what BOLD fMRI can tell us about underlying neuronal activity, and how advanced modelling techniques have improved our ability to use and interpret BOLD. We also highlight areas of controversy in understanding BOLD and suggest research directions required to resolve these issues.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574302

  20. Composite alginate gels for tunable cellular microenvironment mechanics

    PubMed Central

    Khavari, Adele; Nydén, Magnus; Weitz, David A.; Ehrlicher, Allen J.

    2016-01-01

    The mechanics of the cellular microenvironment can be as critical as biochemistry in directing cell behavior. Many commonly utilized materials derived from extra-cellular-matrix create excellent scaffolds for cell growth, however, evaluating the relative mechanical and biochemical effects independently in 3D environments has been difficult in frequently used biopolymer matrices. Here we present 3D sodium alginate hydrogel microenvironments over a physiological range of stiffness (E = 1.85 to 5.29 kPa), with and without RGD binding sites or collagen fibers. We use confocal microscopy to measure the growth of multi-cellular aggregates (MCAs), of increasing metastatic potential in different elastic moduli of hydrogels, with and without binding factors. We find that the hydrogel stiffness regulates the growth and morphology of these cell clusters; MCAs grow larger and faster in the more rigid environments similar to cancerous breast tissue (E = 4–12 kPa) as compared to healthy tissue (E = 0.4–2 kpa). Adding binding factors from collagen and RGD peptides increases growth rates, and change maximum MCA sizes. These findings demonstrate the utility of these independently tunable mechanical/biochemistry gels, and that mechanical confinement in stiffer microenvironments may increase cell proliferation. PMID:27484403

  1. Acetazolamide Mitigates Astrocyte Cellular Edema Following Mild Traumatic Brain Injury.

    PubMed

    Sturdivant, Nasya M; Smith, Sean G; Ali, Syed F; Wolchok, Jeffrey C; Balachandran, Kartik

    2016-01-01

    Non-penetrating or mild traumatic brain injury (mTBI) is commonly experienced in accidents, the battlefield and in full-contact sports. Astrocyte cellular edema is one of the major factors that leads to high morbidity post-mTBI. Various studies have reported an upregulation of aquaporin-4 (AQP4), a water channel protein, following brain injury. AZA is an antiepileptic drug that has been shown to inhibit AQP4 expression and in this study we investigate the drug as a therapeutic to mitigate the extent of mTBI induced cellular edema. We hypothesized that mTBI-mediated astrocyte dysfunction, initiated by increased intracellular volume, could be reduced when treated with AZA. We tested our hypothesis in a three-dimensional in vitro astrocyte model of mTBI. Samples were subject to no stretch (control) or one high-speed stretch (mTBI) injury. AQP4 expression was significantly increased 24 hours after mTBI. mTBI resulted in a significant increase in the cell swelling within 30 min of mTBI, which was significantly reduced in the presence of AZA. Cell death and expression of S100B was significantly reduced when AZA was added shortly before mTBI stretch. Overall, our data point to occurrence of astrocyte swelling immediately following mTBI, and AZA as a promising treatment to mitigate downstream cellular mortality. PMID:27623738

  2. Complex Event Recognition Architecture

    NASA Technical Reports Server (NTRS)

    Fitzgerald, William A.; Firby, R. James

    2009-01-01

    Complex Event Recognition Architecture (CERA) is the name of a computational architecture, and software that implements the architecture, for recognizing complex event patterns that may be spread across multiple streams of input data. One of the main components of CERA is an intuitive event pattern language that simplifies what would otherwise be the complex, difficult tasks of creating logical descriptions of combinations of temporal events and defining rules for combining information from different sources over time. In this language, recognition patterns are defined in simple, declarative statements that combine point events from given input streams with those from other streams, using conjunction, disjunction, and negation. Patterns can be built on one another recursively to describe very rich, temporally extended combinations of events. Thereafter, a run-time matching algorithm in CERA efficiently matches these patterns against input data and signals when patterns are recognized. CERA can be used to monitor complex systems and to signal operators or initiate corrective actions when anomalous conditions are recognized. CERA can be run as a stand-alone monitoring system, or it can be integrated into a larger system to automatically trigger responses to changing environments or problematic situations.

  3. Seismic event classification system

    DOEpatents

    Dowla, F.U.; Jarpe, S.P.; Maurer, W.

    1994-12-13

    In the computer interpretation of seismic data, the critical first step is to identify the general class of an unknown event. For example, the classification might be: teleseismic, regional, local, vehicular, or noise. Self-organizing neural networks (SONNs) can be used for classifying such events. Both Kohonen and Adaptive Resonance Theory (ART) SONNs are useful for this purpose. Given the detection of a seismic event and the corresponding signal, computation is made of: the time-frequency distribution, its binary representation, and finally a shift-invariant representation, which is the magnitude of the two-dimensional Fourier transform (2-D FFT) of the binary time-frequency distribution. This pre-processed input is fed into the SONNs. These neural networks are able to group events that look similar. The ART SONN has an advantage in classifying the event because the types of cluster groups do not need to be pre-defined. The results from the SONNs together with an expert seismologist's classification are then used to derive event classification probabilities. 21 figures.

  4. Seismic event classification system

    DOEpatents

    Dowla, Farid U.; Jarpe, Stephen P.; Maurer, William

    1994-01-01

    In the computer interpretation of seismic data, the critical first step is to identify the general class of an unknown event. For example, the classification might be: teleseismic, regional, local, vehicular, or noise. Self-organizing neural networks (SONNs) can be used for classifying such events. Both Kohonen and Adaptive Resonance Theory (ART) SONNs are useful for this purpose. Given the detection of a seismic event and the corresponding signal, computation is made of: the time-frequency distribution, its binary representation, and finally a shift-invariant representation, which is the magnitude of the two-dimensional Fourier transform (2-D FFT) of the binary time-frequency distribution. This pre-processed input is fed into the SONNs. These neural networks are able to group events that look similar. The ART SONN has an advantage in classifying the event because the types of cluster groups do not need to be pre-defined. The results from the SONNs together with an expert seismologist's classification are then used to derive event classification probabilities.

  5. Cellular automata modeling of weld solidification structure

    SciTech Connect

    Dress, W.B.; Zacharia, T.; Radhakrishnan, B.

    1993-12-31

    The authors explore the use of cellular automata in modeling arc-welding processes. A brief discussion of cellular automata and their previous use in micro-scale solidification simulations is presented. Macro-scale thermal calculations for arc-welding at a thin plate are shown to give good quantitative and qualitative results. Combining the two calculations in a single cellular array provides a realistic simulation of grain growth in a welding process. Results of simulating solidification in a moving melt pool in a poly-crystalline alloy sheet are presented.

  6. Passive Noise Filtering by Cellular Compartmentalization.

    PubMed

    Stoeger, Thomas; Battich, Nico; Pelkmans, Lucas

    2016-03-10

    Chemical reactions contain an inherent element of randomness, which presents itself as noise that interferes with cellular processes and communication. Here we discuss the ability of the spatial partitioning of molecular systems to filter and, thus, remove noise, while preserving regulated and predictable differences between single living cells. In contrast to active noise filtering by network motifs, cellular compartmentalization is highly effective and easily scales to numerous systems without requiring a substantial usage of cellular energy. We will use passive noise filtering by the eukaryotic cell nucleus as an example of how this increases predictability of transcriptional output, with possible implications for the evolution of complex multicellularity. PMID:26967282

  7. Nanomechanics of magnetically driven cellular endocytosis

    NASA Astrophysics Data System (ADS)

    Zablotskii, V.; Lunov, O.; Dejneka, A.; Jastrabík, L.; Polyakova, T.; Syrovets, T.; Simmet, Th.

    2011-10-01

    Being essential for many pharmacodynamic and pharmacokinetic processes and playing a crucial role in regulating substrate detachment that enables cellular locomotion, endocytotic mechanisms in many aspects still remain a mystery and therefore can hardly be controlled. Here, we report on experimental and modeling studies of the magnetically assisted endocytosis of functionalized superparamagnetic iron oxide nanoparticles by prostate cancer cells (PC-3) and characterize the time and force scales of the cellular uptake machinery. The results indicate how the cellular uptake rate could be controlled by applied magnetic field, membrane elasticity, and nanoparticle magnetic moment.

  8. Cellular solidification in a monotectic system

    NASA Technical Reports Server (NTRS)

    Kaukler, W. F.; Curreri, P. A.

    1987-01-01

    Succinonitrile-glycerol, SN-G, transparent organic monotectic alloy is studied with particular attention to cellular growth. The phase diagram is determined, near the monotectic composition, with greater accuracy than previous studies. A solidification interface stability diagram is determined for planar growth. The planar-to-cellular transition is compared to predictions from the Burton, Primm, Schlichter theory. A new technique to determine the solute segregation by Fourier transform infrared spectroscopy is developed. Proposed models that involve the cellular interface for alignment of monotectic second-phase spheres or rods are compared with observations.

  9. Cellular and molecular mechanisms in kidney fibrosis

    PubMed Central

    Duffield, Jeremy S.

    2014-01-01

    Fibrosis is a characteristic feature of all forms of chronic kidney disease. Deposition of pathological matrix in the interstitial space and within the walls of glomerular capillaries as well as the cellular processes resulting in this deposition are increasingly recognized as important factors amplifying kidney injury and accelerating nephron demise. Recent insights into the cellular and molecular mechanisms of fibrogenesis herald the promise of new therapies to slow kidney disease progression. This review focuses on new findings that enhance understanding of cellular and molecular mechanisms of fibrosis, the characteristics of myofibroblasts, their progenitors, and molecular pathways regulating both fibrogenesis and its resolution. PMID:24892703

  10. Toward Joint Hypothesis-Tests Seismic Event Screening Analysis: Ms|mb and Event Depth

    SciTech Connect

    Anderson, Dale; Selby, Neil

    2012-08-14

    Well established theory can be used to combine single-phenomenology hypothesis tests into a multi-phenomenology event screening hypothesis test (Fisher's and Tippett's tests). Commonly used standard error in Ms:mb event screening hypothesis test is not fully consistent with physical basis. Improved standard error - Better agreement with physical basis, and correctly partitions error to include Model Error as a component of variance, correctly reduces station noise variance through network averaging. For 2009 DPRK test - Commonly used standard error 'rejects' H0 even with better scaling slope ({beta} = 1, Selby et al.), improved standard error 'fails to rejects' H0.

  11. Emergence of event cascades in inhomogeneous networks.

    PubMed

    Onaga, Tomokatsu; Shinomoto, Shigeru

    2016-01-01

    There is a commonality among contagious diseases, tweets, and neuronal firings that past events facilitate the future occurrence of events. The spread of events has been extensively studied such that the systems exhibit catastrophic chain reactions if the interaction represented by the ratio of reproduction exceeds unity; however, their subthreshold states are not fully understood. Here, we report that these systems are possessed by nonstationary cascades of event-occurrences already in the subthreshold regime. Event cascades can be harmful in some contexts, when the peak-demand causes vaccine shortages, heavy traffic on communication lines, but may be beneficial in other contexts, such that spontaneous activity in neural networks may be used to generate motion or store memory. Thus it is important to comprehend the mechanism by which such cascades appear, and consider controlling a system to tame or facilitate fluctuations in the event-occurrences. The critical interaction for the emergence of cascades depends greatly on the network structure in which individuals are connected. We demonstrate that we can predict whether cascades may emerge, given information about the interactions between individuals. Furthermore, we develop a method of reallocating connections among individuals so that event cascades may be either impeded or impelled in a network. PMID:27625183

  12. Common features in diverse insect clocks.

    PubMed

    Numata, Hideharu; Miyazaki, Yosuke; Ikeno, Tomoko

    2015-01-01

    This review describes common features among diverse biological clocks in insects, including circadian, circatidal, circalunar/circasemilunar, and circannual clocks. These clocks control various behaviors, physiological functions, and developmental events, enabling adaptation to periodic environmental changes. Circadian clocks also function in time-compensation for celestial navigation and in the measurement of day or night length for photoperiodism. Phase response curves for such clocks reported thus far exhibit close similarities; specifically, the circannual clock in Anthrenus verbasci shows striking similarity to circadian clocks in its phase response. It is suggested that diverse biological clocks share physiological properties in their phase responses irrespective of period length. Molecular and physiological mechanisms are best understood for the optic-lobe and mid-brain circadian clocks, although there is no direct evidence that these clocks are involved in rhythmic phenomena other than circadian rhythms in daily events. Circadian clocks have also been localized in peripheral tissues, and research on their role in various rhythmic phenomena has been started. Although clock genes have been identified as controllers of circadian rhythms in daily events, some of these genes have also been shown to be involved in photoperiodism and possibly in time-compensated celestial navigation. In contrast, there is no experimental evidence indicating that any known clock gene is involved in biological clocks other than circadian clocks. PMID:26605055

  13. Competence across Europe: Highest Common Factor or Lowest Common Denominator?

    ERIC Educational Resources Information Center

    Winterton, Jonathan

    2009-01-01

    Purpose: The purpose of this article is to explore diversity in competence models across Europe and consider the extent to which there is sufficient common ground for a common European approach to underpin the European Qualifications Framework. Design/methodology/approach: The paper uses a literature review and interviews with policy makers.…

  14. Constructing the Commons: Practical Projects To Build the Information Commons.

    ERIC Educational Resources Information Center

    Lee, Daniel R.

    2003-01-01

    Describes several projects aimed at building the Information Commons, including: Knowledge Conservancy plans to create a database of all freely available digitized content; the Universal Library, a project with the long-term goal of providing free, online access to all books; and several projects of the Creative Commons intended to build a robust…

  15. Concepts of event-by-event analysis

    SciTech Connect

    Stroebele, H.

    1995-07-15

    The particles observed in the final state of nuclear collisions can be divided into two classes: those which are susceptible to strong interactions and those which are not, like leptons and the photon. The bulk properties of the {open_quotes}matter{close_quotes} in the reaction zone may be read-off the kinematical characteristics of the particles observable in the final state. These characteristics are strongly dependent on the last interaction these particles have undergone. In a densly populated reaction zone strongly interacting particles will experience many collisions after they have been formed and before they emerge into the asymptotic final state. For the particles which are not sensitive to strong interactions their formation is also their last interaction. Thus photons and leptons probe the period during which they are produced whereas hadrons reflect the so called freeze-out processes, which occur during the late stage in the evolution of the reaction when the population density becomes small and the mean free paths long. The disadvantage of the leptons and photons is their small production cross section; they cannot be used in an analysis of the characteristics of individual collision events, because the number of particles produced per event is too small. The hadrons, on the other hand, stem from the freeze-out period. Information from earlier periods requires multiparticle observables in the most general sense. It is one of the challenges of present day high energy nuclear physics to establish and understand global observables which differentiate between mere hadronic scenarios, i.e superposition of hadronic interactions, and the formation of a partonic (short duration) steady state which can be considered a new state of matter, the Quark-Gluon Plasma.

  16. The partly Aalen's model for recurrent event data with a dependent terminal event.

    PubMed

    Chen, Chyong-Mei; Shen, Pao-Sheng; Chuang, Ya-Wen

    2016-01-30

    Recurrent event data are commonly observed in biomedical longitudinal studies. In many instances, there exists a terminal event, which precludes the occurrence of additional repeated events, and usually there is also a nonignorable correlation between the terminal event and recurrent events. In this article, we propose a partly Aalen's additive model with a multiplicative frailty for the rate function of recurrent event process and assume a Cox frailty model for terminal event time. A shared gamma frailty is used to describe the correlation between the two types of events. Consequently, this joint model can provide the information of temporal influence of absolute covariate effects on the rate of recurrent event process, which is usually helpful in the decision-making process for physicians. An estimating equation approach is developed to estimate marginal and association parameters in the joint model. The consistency of the proposed estimator is established. Simulation studies demonstrate that the proposed approach is appropriate for practical use. We apply the proposed method to a peritonitis cohort data set for illustration. PMID:26265213

  17. Characterizing an "uncharacteristic" ETS event in northern Cascadia

    USGS Publications Warehouse

    Wang, Kelin; Dragert, Herb; Kao, Honn; Roeloffs, Evelyn

    2008-01-01

    GPS and borehole strainmeter data allowed the detection and model characterization of a slow slip event in northern Cascadia in November 2006 accompanying a brief episode of seismic tremor. The event is much smaller in area and duration than other well-known ETS events in northern Cascadia but is strikingly similar to typical ETS events at the Nankai subduction zone. The 30-45 km depth range and the 2-3 cm slip magnitude as interpreted for this event appear to be common to most ETS events in these two subduction zones, regardless of their sizes. We infer that the Nankai-type small ETS events must be abundant at Cascadia and that ETS events at the two subduction zones are governed by a similar physical process.

  18. Characterizing an "uncharacteristics" ETS event in northern Cascadia

    USGS Publications Warehouse

    Wang, K.; Dragert, H.; Kao, H.; Roeloffs, E.

    2008-01-01

    GPS and borehole strainmeter data allowed the detection and model characterization of a slow slip event in northern Cascadia in November 2006 accompanying a brief episode of seismic tremor. The event is much smaller in area and duration than other well-known ETS events in northern Cascadia but is strikingly similar to typical ETS events at the Nankai subduction zone. The 30-45 km depth range and the 2-3 cm slip magnitude as interpreted for this event appear to be common to most ETS events in these two subduction zones, regardless of their sizes. We infer that the Nankai-type small ETS events must be abundant at Cascadia and that ETS event at the two subduction zones are governed by a similar physical process. Copyright 2008 by the American Geophysical Union.

  19. Lunar and Martian hardware commonality

    NASA Technical Reports Server (NTRS)

    Davis, Hubert P.; Johnson, Robert E.; Phillips, Paul G.; Spear, Donald S.; Stump, William R.; Williams, Franklin U.

    1986-01-01

    A number of different hardware elements were examined for possible Moon/Mars program commonality. These include manned landers; cargo landers, a trans-Mars injection (TMI) stage, traverse vehicles, unmanned surface rovers, habitation modules, and power supplies. Preliminary analysis indicates that it is possible to build a common two-stage manned lander. A single-stage, reusable lander may be practical for the lunar cast, but much less so for the Martian case, and commonality may therefore exist only at the subsystem level. A modified orbit transfer vehicle was examined as a potential cargo lander. Potential cargoes to various destinations were calculated for a Shuttle external tank sized TMI stage. A nuclear powered, long range traverse vehicle was conceptually designed and commonality is considered feasible. Short range, unmanned rovers can be made common without great effort. A surface habitation module may be difficult to make common due to difficulties in landing certain shapes on the Martian surface with aerobraking landers. Common nuclear power sources appear feasible. High temperature radiators appear easy to make common. Low temperature radiators may be difficult to make common. In most of these cases, Martian requirements determine the design.

  20. Chromatin dynamics during cellular differentiation in the female reproductive lineage of flowering plants.

    PubMed

    Baroux, Célia; Autran, Daphné

    2015-07-01

    Sexual reproduction in flowering plants offers a number of remarkable aspects to developmental biologists. First, the spore mother cells - precursors of the plant reproductive lineage - are specified late in development, as opposed to precocious germline isolation during embryogenesis in most animals. Second, unlike in most animals where meiosis directly produces gametes, plant meiosis entails the differentiation of a multicellular, haploid gametophyte, within which gametic as well as non-gametic accessory cells are formed. These observations raise the question of the factors inducing and modus operandi of cell fate transitions that originate in floral tissues and gametophytes, respectively. Cell fate transitions in the reproductive lineage imply cellular reprogramming operating at the physiological, cytological and transcriptome level, but also at the chromatin level. A number of observations point to large-scale chromatin reorganization events associated with cellular differentiation of the female spore mother cells and of the female gametes. These include a reorganization of the heterochromatin compartment, the genome-wide alteration of the histone modification landscape, and the remodeling of nucleosome composition. The dynamic expression of DNA methyltransferases and actors of small RNA pathways also suggest additional, global epigenetic alterations that remain to be characterized. Are these events a cause or a consequence of cellular differentiation, and how do they contribute to cell fate transition? Does chromatin dynamics induce competence for immediate cellular functions (meiosis, fertilization), or does it also contribute long-term effects in cellular identity and developmental competence of the reproductive lineage? This review attempts to review these fascinating questions. PMID:26031902