Phloem unloading follows an extensive apoplasmic pathway in cucumber (Cucumis sativus L.) fruit from anthesis to marketable maturing stage.

PubMed

Hu, Liping; Sun, Huihui; Li, Ruifu; Zhang, Lingyun; Wang, Shaohui; Sui, Xiaolei; Zhang, Zhenxian

2011-11-01

The phloem unloading pathway remains unclear in fruits of Cucurbitaceae, a classical stachyose-transporting species with bicollateral phloem. Using a combination of electron microscopy, transport of phloem-mobile symplasmic tracer carboxyfluorescein, assays of acid invertase and sucrose transporter, and [(14)C]sugar uptake, the phloem unloading pathway was studied in cucumber (Cucumis sativus) fruit from anthesis to the marketable maturing stage. Structural investigations showed that the sieve element-companion cell (SE-CC) complex of the vascular bundles feeding fruit flesh is apparently symplasmically restricted. Imaging of carboxyfluorescein unloading showed that the dye remained confined to the phloem strands of the vascular bundles in the whole fruit throughout the stages examined. A 37 kDa acid invertase was located predominantly in the cell walls of SE-CC complexes and parenchyma cells. Studies of [(14)C]sugar uptake suggested that energy-driven transporters may be functional in sugar trans-membrane transport within symplasmically restricted SE-CC complex, which was further confirmed by the existence of a functional plasma membrane sucrose transporter (CsSUT4) in cucumber fruit. These data provide a clear evidence for an apoplasmic phloem unloading pathway in cucumber fruit. A presumption that putative raffinose or stachyose transporters may be involved in soluble sugars unloading was discussed. © 2011 Blackwell Publishing Ltd.

Bark structure of southern upland oaks

Treesearch

E.T. Howard

1977-01-01

Bark structure of eleven oak species commonly found on southern pine sites was examined and described. In inner bark (phloem), groups of thick-walled lignified fibers and sclereids are interspersed among thin-walled cellulosic elements (parenchyma, sieve tube members, and companion cells). These fibers and sclereids greatly influence the bark's density, hardness,...

Control of female gamete formation by a small RNA pathway in Arabidopsis.

PubMed

Olmedo-Monfil, Vianey; Durán-Figueroa, Noé; Arteaga-Vázquez, Mario; Demesa-Arévalo, Edgar; Autran, Daphné; Grimanelli, Daniel; Slotkin, R Keith; Martienssen, Robert A; Vielle-Calzada, Jean-Philippe

2010-03-25

In the ovules of most sexual flowering plants female gametogenesis is initiated from a single surviving gametic cell, the functional megaspore, formed after meiosis of the somatically derived megaspore mother cell (MMC). Because some mutants and certain sexual species exhibit more than one MMC, and many others are able to form gametes without meiosis (by apomixis), it has been suggested that somatic cells in the ovule are competent to respond to a local signal likely to have an important function in determination. Here we show that the Arabidopsis protein ARGONAUTE 9 (AGO9) controls female gamete formation by restricting the specification of gametophyte precursors in a dosage-dependent, non-cell-autonomous manner. Mutations in AGO9 lead to the differentiation of multiple gametic cells that are able to initiate gametogenesis. The AGO9 protein is not expressed in the gamete lineage; instead, it is expressed in cytoplasmic foci of somatic companion cells. Mutations in SUPPRESSOR OF GENE SILENCING 3 and RNA-DEPENDENT RNA POLYMERASE 6 exhibit an identical defect to ago9 mutants, indicating that the movement of small RNA (sRNAs) silencing out of somatic companion cells is necessary for controlling the specification of gametic cells. AGO9 preferentially interacts with 24-nucleotide sRNAs derived from transposable elements (TEs), and its activity is necessary to silence TEs in female gametes and their accessory cells. Our results show that AGO9-dependent sRNA silencing is crucial to specify cell fate in the Arabidopsis ovule, and that epigenetic reprogramming in companion cells is necessary for sRNA-dependent silencing in plant gametes.

The rendez-vous of mobile sieve-element and abundant companion-cell proteins.

PubMed

De Marco, Federica; Le Hir, Rozenn; Dinant, Sylvie

2018-06-01

Thousands of sieve tube exudate proteins (STEP) have now been identified and predicted to fulfill a diversity of functions. However, most STEPs should be considered putative, since methods to collect sieve tube exudates have many technical drawbacks, and advanced functional characterization will be required to distinguish contaminant from bonafide proteins, and determine the latter's location and activity in sieve elements (SE). One major challenge is to develop new approaches to elucidate the function of these SE proteins, which in turn, is expected to shed light on intriguing aspects of SE cell biology. Copyright © 2018 Elsevier Ltd. All rights reserved.

Effect of small-molecule modification on single-cell pharmacokinetics of PARP inhibitors.

PubMed

Thurber, Greg M; Reiner, Thomas; Yang, Katherine S; Kohler, Rainer H; Weissleder, Ralph

2014-04-01

The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging, given the complex tumor microenvironment including intra- and intertumor heterogeneity. The difficulty in studying this distribution is even more significant for small-molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small-molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model.

Effect of Small Molecule Modification on Single Cell Pharmacokinetics of PARP Inhibitors

PubMed Central

Thurber, Greg M.; Reiner, Thomas; Yang, Katherine S; Kohler, Rainer; Weissleder, Ralph

2014-01-01

The heterogeneous delivery of drugs in tumors is an established process contributing to variability in treatment outcome. Despite the general acceptance of variable delivery, the study of the underlying causes is challenging given the complex tumor microenvironment including intra- and inter-tumor heterogeneity. The difficulty in studying this distribution is even more significant for small molecule drugs where radiolabeled compounds or mass spectrometry detection lack the spatial and temporal resolution required to quantify the kinetics of drug distribution in vivo. In this work, we take advantage of the synthesis of fluorescent drug conjugates that retain their target binding but are designed with different physiochemical and thus pharmacokinetic properties. Using these probes, we followed the drug distribution in cell culture and tumor xenografts with temporal resolution of seconds and subcellular spatial resolution. These measurements, including in vivo permeability of small molecule drugs, can be used directly in predictive pharmacokinetic models for the design of therapeutics and companion imaging agents as demonstrated by a finite element model. PMID:24552776

Viral and Cellular Factors Involved in Phloem Transport of Plant Viruses

PubMed Central

Hipper, Clémence; Brault, Véronique; Ziegler-Graff, Véronique; Revers, Frédéric

2013-01-01

Phloem transport of plant viruses is an essential step in the setting-up of a complete infection of a host plant. After an initial replication step in the first cells, viruses spread from cell-to-cell through mesophyll cells, until they reach the vasculature where they rapidly move to distant sites in order to establish the infection of the whole plant. This last step is referred to as systemic transport, or long-distance movement, and involves virus crossings through several cellular barriers: bundle sheath, vascular parenchyma, and companion cells for virus loading into sieve elements (SE). Viruses are then passively transported within the source-to-sink flow of photoassimilates and are unloaded from SE into sink tissues. However, the molecular mechanisms governing virus long-distance movement are far from being understood. While most viruses seem to move systemically as virus particles, some viruses are transported in SE as viral ribonucleoprotein complexes (RNP). The nature of the cellular and viral factors constituting these RNPs is still poorly known. The topic of this review will mainly focus on the host and viral factors that facilitate or restrict virus long-distance movement. PMID:23745125

In Vivo Quantification of Cell Coupling in Plants with Different Phloem-Loading Strategies[W][OA

PubMed Central

Liesche, Johannes; Schulz, Alexander

2012-01-01

Uptake of photoassimilates into the leaf phloem is the key step in carbon partitioning and phloem transport. Symplasmic and apoplasmic loading strategies have been defined in different plant taxa based on the abundance of plasmodesmata between mesophyll and phloem. For apoplasmic loading to occur, an absence of plasmodesmata is a sufficient but not a necessary criterion, as passage of molecules through plasmodesmata might well be blocked or restricted. Here, we present a noninvasive, whole-plant approach to test symplasmic coupling and quantify the intercellular flux of small molecules using photoactivation microscopy. Quantification of coupling between all cells along the prephloem pathways of the apoplasmic loader Vicia faba and Nicotiana tabacum showed, to our knowledge for the first time in vivo, that small solutes like sucrose can diffuse through plasmodesmata up to the phloem sieve element companion cell complex (SECCC). As expected, the SECCC was found to be symplasmically isolated for small solutes. In contrast, the prephloem pathway of the symplasmic loader Cucurbita maxima was found to be well coupled with the SECCC. Phloem loading in gymnosperms is not well understood, due to a profoundly different leaf anatomy and a scarcity of molecular data compared with angiosperms. A cell-coupling analysis for Pinus sylvestris showed high symplasmic coupling along the entire prephloem pathway, comprising at least seven cell border interfaces between mesophyll and sieve elements. Cell coupling together with measurements of leaf sap osmolality indicate a passive symplasmic loading type. Similarities and differences of this loading type with that of angiosperm trees are discussed. PMID:22422939

The problem of the barium stars

NASA Technical Reports Server (NTRS)

Bohm-Vitense, E.; Nemec, J.; Proffitt, C.

1984-01-01

Ultraviolet observations of barium stars and other cool stars with peculiar element abundances are reported. Those observations attempted to find hot white dwarf companions. Among six real barium stars studied, only Zeta Cap was found to have a white dwarf companion. Among seven mild, or marginal, barium stars studied, at least three were found to have hot subluminous companions. It is likely that all of them have white dwarf companions.

Companion Protease Inhibitors for the In Situ Protection of Recombinant Proteins in Plants.

PubMed

Robert, Stéphanie; Jutras, Philippe V; Khalf, Moustafa; D'Aoust, Marc-André; Goulet, Marie-Claire; Sainsbury, Frank; Michaud, Dominique

2016-01-01

We previously described a procedure for the use of plant protease inhibitors as "companion" accessory proteins to prevent unwanted proteolysis of clinically useful recombinant proteins in leaf crude protein extracts (Benchabane et al. Methods Mol Biol 483:265-273, 2009). Here we describe the use of these inhibitors for the protection of recombinant proteins in planta, before their extraction from leaf tissues. A procedure is first described involving inhibitors co-expressed along-and co-migrating-with the protein of interest in host plant cells. An alternative, single transgene scheme is then described involving translational fusions of the recombinant protein and companion inhibitor. These approaches may allow for a significant improvement of protein steady-state levels in leaves, comparable to yield improvements observed with protease-deficient strains of less complex protein expression hosts such as E. coli or yeasts.

Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

PubMed Central

van de Stolpe, Anja; den Toonder, Jaap M. J.

2014-01-01

Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics. PMID:24879438

Lichen physiology and cell biology

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, D.H.

1985-01-01

This book presents information on topics relating to mineral element accumulation in bog lichens, nitrogen losses from diazotrophic lichens, influence of automobile exhaust and lead on the oxygen exchange of lichens, temporal variation in lichen element levels, and lead and uranium uptake by lichens. Other topics include the architecture of the concentric bodies in the mycobiont of Peltigera praetextata; multiple enzyme forms in lichens, photosynthesis, water relations multiple enzyme forms in lichens, photosynthesis, water relations and thallus structure of strictaceae lichens; and aspects of carbohydrate metabolism in lichens. The distribution of uranium and companion elements in lichen heath associated withmore » undisturbed uranium deposits in the Canadian Arctic is also discussed.« less

Study on ductility dip cracking susceptibility in Filler Metal 82 during welding

NASA Astrophysics Data System (ADS)

Chen, Jing-Qing; Lu, Hao; Cui, Wei

2011-06-01

In this paper, Ductility Dip Cracking (DDC) susceptibility in Inconel600 companion Filler Metal 82 (FM82) under different stress states is investigated. Inconel600 is a Ni-Cr-Fe alloy with excellent resistance to general corrosion, localized corrosion, and stress corrosion, which has been widely used in nuclear power plants. However, the companion FM82 has been shown to be susceptible to DDC in welding process. To resolve the problem, this work is mainly focused on evaluating DDC susceptibility in FM82 in welding process. First of all, Strain to Fracture (STF) test is used to achieve the DDC criterion under simple stress state, and the formation mechanism of DDC was explained. Real welding is a process with complex stress state. Later, to get the DDC susceptibility under complex stress state, models about multi-pass welding were built up by means of finite element method. According to numerical simulation results, relationship of deformation and temperature history is achieved. Moreover, susceptible locations and moments could be determined associated with STF results. The simulation results fairly agree with welding experiment from another research.

A tale of two neglected systems-structure and function of the thin- and thick-walled sieve tubes in monocotyledonous leaves.

PubMed

Botha, C E J

2013-01-01

There is a large body of information relating to the ontogeny, development and the vasculature of eudicotyledonous leaves. However, there is less information available concerning the vascular anatomy of monocotyledonous leaves. This is surprising, given that there are two uniquely different phloem systems present in large groups such as grasses and sedges. Monocotyledonous leaves contain marginal, large, intermediate, and small longitudinal veins that are interconnected by numerous transverse veins. The longitudinal veins contain two metaphloem sieve tube types, which, based upon their ontogeny and position within the phloem, are termed early (thin-walled) and late (thick-walled) sieve tubes. Early metaphloem comprises sieve tubes, companion cells and vascular parenchyma (VP) cells, whilst the late metaphloem, contains thick-walled sieve tubes (TSTs) that lack companion cells. TSTs are generally adjacent to, or no more than one cell removed from the metaxylem. Unlike thin-walled sieve tube (ST) -companion cell complexes, TSTs are connected to parenchyma by pore-plasmodesma units and are generally symplasmically isolated from the STs. This paper addresses key structural and functional differences between thin- and thick-walled sieve tubes and explores the unique advantages of alternate transport strategies that this 5-7 million years old dual system may offer. It would seem that these two systems may enhance, add to, or play a significant role in increasing the efficiency of solute retrieval as well as of assimilate transfer.

A tale of two neglected systems—structure and function of the thin- and thick-walled sieve tubes in monocotyledonous leaves

PubMed Central

Botha, C. E. J.

2013-01-01

There is a large body of information relating to the ontogeny, development and the vasculature of eudicotyledonous leaves. However, there is less information available concerning the vascular anatomy of monocotyledonous leaves. This is surprising, given that there are two uniquely different phloem systems present in large groups such as grasses and sedges. Monocotyledonous leaves contain marginal, large, intermediate, and small longitudinal veins that are interconnected by numerous transverse veins. The longitudinal veins contain two metaphloem sieve tube types, which, based upon their ontogeny and position within the phloem, are termed early (thin-walled) and late (thick-walled) sieve tubes. Early metaphloem comprises sieve tubes, companion cells and vascular parenchyma (VP) cells, whilst the late metaphloem, contains thick-walled sieve tubes (TSTs) that lack companion cells. TSTs are generally adjacent to, or no more than one cell removed from the metaxylem. Unlike thin-walled sieve tube (ST) -companion cell complexes, TSTs are connected to parenchyma by pore-plasmodesma units and are generally symplasmically isolated from the STs. This paper addresses key structural and functional differences between thin- and thick-walled sieve tubes and explores the unique advantages of alternate transport strategies that this 5–7 million years old dual system may offer. It would seem that these two systems may enhance, add to, or play a significant role in increasing the efficiency of solute retrieval as well as of assimilate transfer. PMID:23964280

Escherichia coli serotype O157:H7 retention on solid surfaces and peroxide resistance is enhanced by dual-strain biofilm formation.

PubMed

Uhlich, Gaylen A; Rogers, Donna P; Mosier, Derek A

2010-08-01

In a previous study we showed that an Escherichia coli O157:H7 strain that was unable to form biofilm was retained in large numbers in dual-strain biofilms formed with an E. coli O-:H4 companion strain. In this study we tested additional companion strains for their ability to retain E. coli O157:H7 strain 0475s. Companion strains producing biofilm that withstood aggressive washes were able to significantly increase serotype O157:H7 retention. Dual-strain biofilms with certain companion strains retained higher percentages of strain 0475s, and that ability was independent of biofilm total cell numbers. Tests with additional non-biofilm-forming E. coli O157:H7 strains showed that enhancement by companion strains was not unique to strain 0475s. Experiments using an E. coli companion strain with deletions of various curli and cellulose genes indicated that dual-strain biofilm formation was dependent on companion strain properties. Strain 0475s was not able to generate biofilm or persist on plastic when grown in broth with a biofilm-forming companion and separated by a 0.2 microm porous membrane, indicating a requirement for intimate contact with the companion strain. When dual-strain biofilms and planktonic cells were challenged with 5% H(2)O(2), strain 0475 showed greater survival in biofilms with certain companion strains compared to the corresponding planktonic cells. The results of this study indicate that non-biofilm-forming E. coli O157:H7 strains are retained on solid surfaces associated with biofilms generated by companion strains. However, properties other than biofilm mass enable certain companion strains to retain greater numbers of E. coli O157:H7.

A conversation across generations: soma-germ cell crosstalk in plants.

PubMed

Feng, Xiaoqi; Zilberman, Daniel; Dickinson, Hugh

2013-02-11

Plants undergo alternation of generation in which reproductive cells develop in the plant body ("sporophytic generation") and then differentiate into a multicellular gamete-forming "gametophytic generation." Different populations of helper cells assist in this transgenerational journey, with somatic tissues supporting early development and single nurse cells supporting gametogenesis. New data reveal a two-way relationship between early reproductive cells and their helpers involving complex epigenetic and signaling networks determining cell number and fate. Later, the egg cell plays a central role in specifying accessory cells, whereas in both gametophytes, companion cells contribute non-cell-autonomously to the epigenetic landscape of the gamete genomes. Copyright © 2013 Elsevier Inc. All rights reserved.

CellMiner Companion: an interactive web application to explore CellMiner NCI-60 data.

PubMed

Wang, Sufang; Gribskov, Michael; Hazbun, Tony R; Pascuzzi, Pete E

2016-08-01

The NCI-60 human tumor cell line panel is an invaluable resource for cancer researchers, providing drug sensitivity, molecular and phenotypic data for a range of cancer types. CellMiner is a web resource that provides tools for the acquisition and analysis of quality-controlled NCI-60 data. CellMiner supports queries of up to 150 drugs or genes, but the output is an Excel file for each drug or gene. This output format makes it difficult for researchers to explore the data from large queries. CellMiner Companion is a web application that facilitates the exploration and visualization of output from CellMiner, further increasing the accessibility of NCI-60 data. The web application is freely accessible at https://pul-bioinformatics.shinyapps.io/CellMinerCompanion The R source code can be downloaded at https://github.com/pepascuzzi/CellMinerCompanion.git ppascuzz@purdue.edu Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Three new barium dwarfs with white dwarf companions: BD+68°1027, RE J0702+129 and BD+80°670

NASA Astrophysics Data System (ADS)

Kong, X. M.; Bharat Kumar, Y.; Zhao, G.; Zhao, J. K.; Fang, X. S.; Shi, J. R.; Wang, L.; Zhang, J. B.; Yan, H. L.

2018-02-01

We report three new barium (Ba) dwarfs lying in Sirius-like systems. They provide direct evidence that Ba dwarfs are companions to white dwarfs (WDs). Atmospheric parameters, stellar masses and the chemical abundances of 25 elements, including light, α, Fe-peak and s-process elements, are derived from high-resolution and high S/N spectra. The enhancement of s-process elements with [s/Fe] ratios between 0.4 and 0.6 confirm them as mild barium stars. The estimated metallicities (-0.31, -0.06 and 0.13) of BD+68°1027, RE J0702+129 and BD+80°670 are in the range of known Ba dwarfs and giants. As expected, the observed indices [hs/ls], [s/Fe] and [C/Fe] show an anti-correlation with metallicity. Asymptotic giant branch (AGB) progenitor masses are estimated for the WD companions of RE J0702+129 (1.47 M⊙) and BD+80°670 (3.59 M⊙). These confirm the predicted range of progenitor AGB masses (1.5-4 M⊙) for unseen WDs around Ba dwarfs. The surface abundances of s-process elements in RE J0702+129 and BD+80°670 are compared with AGB models and they are in close agreement, within the predicted accretion efficiencies and pollution factors for Ba stars. These results support that the origin of s-process overabundances in Ba dwarfs is similar to those of Ba giants via the McClure hypothesis in which Ba stars accumulate s-process elements through mass transfer from their host companions during the AGB phase.

The orbit and companion of the Cepheid S Sge - A probable triple system

NASA Technical Reports Server (NTRS)

Evans, Nancy R.; Welch, Douglas L.; Slovak, Mark H.; Barnes, Thomas G., III; Moffett, Thomas J.

1993-01-01

New radial velocities for the classical Cepheid S Sge have been obtained and combined with previous observations to derive a new orbit. The revised orbital elements are: gamma, -10.3 +/- 0.4 km/s; K, 15.5 +/- 0.2 km/s; e, 0.23 +/- 0.02; omega, 203.1 +/- 4.2 deg; T0, 39902.3 +/- 6.6 JD; P, 675.79 +/- 0.18 days; f(m), 0.239 +/- 0.010 solar masses; a sin i, 0.935 AU = 139.9 +/- 2.0 x 10 exp 6 km; s.e., 1.2 km/s. The revised elements differ very little from the orbit determined by Herbig and Moore (1952). We have also obtained low resolution IUE spectra to search for the companion. The IUE spectra show excess flux at 1800 A when compared with spectra of the single Cepheid Delta Cep at the same (B-V)0. The spectral type of the companion determined from this flux excess is A7 V to F0 V. However, the mass of such a companion (1.7 to 1.5 solar masses) is smaller than the minimum mass (2.8 solar masses) required by the mass function and an evolutionary mass of the Cepheid. We infer that the companion is itself a short period binary.

Structural and Physiological Changes in Sugar Beet Leaves during Sink to Source Conversion 1

PubMed Central

Fellows, Robert J.; Geiger, Donald R.

1974-01-01

The onset of export during leaf development was correlated with changes in metabolism and ultrastructure and with patterns of solute distribution in the developing seventh leaf of sugar beet (Beta vulgaris L.) in order to study the cause of initiation of translocation. Infrared gas analysis of carbon dioxide uptake showed a broad peak for net photosynthesis dm−2 at 35 to 40% final laminar length. Pulse labeling with 14CO2 demonstrated that maximum import of translocate occurred at 25% final laminar length; export was first observed at 35% final laminar length. Between 40 and 50% final laminar length a rapid increase in amount of export occurred, primarily as a result of the increase in the area of leaf which was exporting. Whole leaf autoradiography revealed that onset of phloem loading spread basipetally from the leaf tip; loading was initiated at about 22% final laminar length and was essentially complete by 50% final laminar length. Those areas which clearly exhibited loading no longer imported from other parts of the plant while the area in transition still appeared to import label from source regions. There was little difference between source and sink leaf tissue in the kinetic parameters Kj and Jmax (30) for uptake of exogenous sucrose supplied via free space. The concentration of solutes in sieve elements and companion cells of the sink leaf was highest in the mature tip area and gradually decreased in the direction of the immature base. There appeared to be no dramatic structural transformation within the phloem of the minor veins that was closely correlated with the time when phloem loading or export began. Rather, there appeared to be a gradual differentiation of phloem which resulted in a sizable proportion of the population of minor vein sieve elements and companion cells attaining maturity in the older sink regions prior to initiation of phloem loading. The area of the leaf undergoing development appeared to exhibit the beginnings of phloem loading 30 to 45 hours prior to onset of export. Import continued into the area in transition until the full level of vein loading was attained. Structural maturation of the phloem and onset of phloem loading are felt to be more preparatory in nature rather than immediately causal events which triggered export. The initiation of export out of a developing leaf, we believe, is the result of the increasing solute content within the sieve element and companion cells of the minor veins, in particular. The higher osmotic pressure in the sieve tubes causes a reversal of the previously inward directed gradient and produces a mass flow, through unobstructed sieve elements, out of the new source region of the leaf. Images PMID:16658993

The Interstellar Medium Properties of Heavily Reddened Quasars & Companions at z ˜ 2.5 with ALMA & JVLA

NASA Astrophysics Data System (ADS)

Banerji, Manda; Jones, Gareth C.; Wagg, Jeff; Carilli, Chris L.; Bisbas, Thomas G.; Hewett, Paul C.

2018-06-01

We study the interstellar medium (ISM) properties of three heavily reddened quasars at z ˜ 2.5 as well as three millimetre-bright companion galaxies near these quasars. New JVLA and ALMA observations constrain the CO(1-0), CO(7-6) and [CI]3P2 - 3P1 line emission as well as the far infrared to radio continuum. The gas excitation and physical properties of the ISM are constrained by comparing our observations to photo-dissociation region (PDR) models. The ISM in our high-redshift quasars is composed of very high-density, high-temperature gas which is already highly enriched in elements like carbon. One of our quasar hosts is shown to be a close-separation (<2″) major merger with different line emission properties in the millimeter-bright galaxy and quasar components. Low angular resolution observations of high-redshift quasars used to assess quasar excitation properties should therefore be interpreted with caution as they could potentially be averaging over multiple components with different ISM conditions. Our quasars and their companion galaxies show a range of CO excitation properties spanning the full extent from starburst-like to quasar-like spectral line energy distributions. We compare gas masses based on CO, CI and dust emission, and find that these can disagree when standard assumptions are made regarding the values of αCO, the gas-to-dust ratio and the atomic carbon abundances. We conclude that the ISM properties of our quasars and their companion galaxies are diverse and likely vary spatially across the full extent of these complex, merging systems.

Re-187 Os-187 Isotopic and Highly Siderophile Element Systematics of Group IVB Irons

NASA Technical Reports Server (NTRS)

Honesto, J.; McDonough, W. F.; Walker, R. J.; McCoy, T. J.; Ash, R. D.

2005-01-01

Study of the magmatic iron meteorite groups permits constraints to be placed on the chemical and isotopic composition of parent bodies, and the timing of, and crystal-liquid fractionation processes involved in the crystallization of asteroidal cores. Here we examine Re-Os isotopic and trace elemental systematics of group IVB irons. Compared to most irons, the irons comprising this group are enriched in some of the most refractory siderophile elements, yet highly-depleted in most volatile siderophile elements. These characteristics have been attributed to processes such as high temperature condensation of precursor materials and oxidation in the parent body. Most recently it has been suggested that both processes may be involved in the chemical complexity of the group. Here, high precision isotopic and highly siderophile element (HSE) concentrations are used to further examine these possible origins, and the crystallization history of the group. In addition, we have begun to assess the possibility of relating certain ungrouped irons with major groups via multi-element, trace element modeling. In a companion abstract, the isotopic and trace element systematics of the ungrouped iron Tishomingo are compared with the IVB irons.

Chemistry and origin of minor and trace elements in selected vitrinite concentrates from bituminous and anthracitic coals

USGS Publications Warehouse

Palmer, C.A.; Lyons, P.C.

1990-01-01

Twelve hand-picked vitrinite concentrates and companion whole-coal samples were analyzed for trace and minor elements by instrumental neutron activation analysis (INAA) and direct-current-arc spectrographic techniques (DCAS). The vitrinite concentrates contained 94 to nearly 100 vol.% vitrinite compared to 71-95 vol.% in the companion whole coals. The ash contents of the vitrinite concentrates were 2 to more than 190 times less than the ash contents of the companion whole coals. Organic and inorganic affinities were determined by comparing the elemental concentrations in the vitrinite concentrates to the concentrations in the companion whole coals. The ratios of these concentrations for 33 selected elements are shown in Figure 1. Ratios greater than 1 indicate organic affinity, and ratios less than 1 indicate inorganic affinity. Br and W generally showed organic affinity in all samples in this study. In the nine samples from the eastern United States (Fig. 1A-C) less than one-fourth of the trace elements show organic affinity compared to nearly one-half for the three English and Australian samples (Fig. 1D). The elements that generally show organic affinity in the non-U.S.A. samples studied include As, Cs, Hf, and Ni, which have generally inorganic affinities in the U.S.A. samples, and Cr, Sb, Se, and U, which have mixed (both organic and inorganic) affinities, in the U.S.A. coals studied, has an inorganic affinity in the English coals studied. B shows organic affinity in the samples from the Illinois basin (Fig. 1C). For the samples studied, Ba shows organic affinity in the Appalachian basin bituminous coals (Fig. 1B), inorganic affinity in the Illinois basin coals, and overall mixed affinities. In all the samples studied, Cu, Mn, Na, Sr, Ta, V, and Zn show mixed affinities, and A1, Co, Eu, Fe, Ga, K, La, Mg, Sc, Si, Th, Ti, and Ub have generally inorganic affinity. ?? 1990.

On the absence of young white dwarf companions to five technetium stars

NASA Technical Reports Server (NTRS)

Smith, Verne V.; Lambert, David L.

1987-01-01

A search for hot companions to five stars of type MS and S has been carried out using the IUE satellite. No hot companions were detected for the MS stars HR 85, 4647, 6702, and 8062, and the S star HR 8714. Limits on the luminosities of possible white dwarf companions provide lower limits of 2-5x10 to the 8th yr to the ages of any degenerate companions. All five stars exhibit strong Tc I lines, and the presence of technetium, with a half-life of 2.1x10 to the 5th yr, signifies recent nucleosynthesis. The limits on the ages of possible white dwarf companions that are equal to or greater than 1000 half-lives of Tc exclude the possibility that the s-process elemental enhancement seen in these MS and S stars resulted from mass transfer from a more highly evolved companion (as is probably the mechanism by which barium stars are created). These MS and S stars represent a sample of true thermally pulsing asymptotic giant-branch stars.

A Poised Chromatin Platform for TGF-[beta] Access to Master Regulators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xi, Qiaoran; Wang, Zhanxin; Zaromytidou, Alexia-Ileana

2012-02-07

Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-{beta} signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compactingmore » factor HP1, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state.« less

Binary Cepheids From High-Angular Resolution

NASA Astrophysics Data System (ADS)

Gallenne, A.; Mérand, A.; Kervella, P.

2015-12-01

Optical interferometry is the only technique giving access to milli-arcsecond (mas) spatial resolution. This is a powerful and unique tool to detect the close orbiting companions of Cepheids, and offers an unique opportunity to make progress in resolving the Cepheid mass discrepancy. Our goal in studying binary Cepheids is to measure the astrometric position of the high-contrast companion, and then combine them with spectroscopic measurements to derive the orbital elements, distances, and dynamical masses. In the course of this program, we developed a new tool, CANDID, to search for high-contrast companions and set detection limits from interferometric observations

Molecular characterization of a phloem-specific gene encoding the filament protein, phloem protein 1 (PP1), from Cucurbita maxima.

PubMed

Clark, A M; Jacobsen, K R; Bostwick, D E; Dannenhoffer, J M; Skaggs, M I; Thompson, G A

1997-07-01

Sieve elements in the phloem of most angiosperms contain proteinaceous filaments and aggregates called P-protein. In the genus Cucurbita, these filaments are composed of two major proteins: PP1, the phloem filament protein, and PP2, the phloem lactin. The gene encoding the phloem filament protein in pumpkin (Cucurbita maxima Duch.) has been isolated and characterized. Nucleotide sequence analysis of the reconstructed gene gPP1 revealed a continuous 2430 bp protein coding sequence, with no introns, encoding an 809 amino acid polypeptide. The deduced polypeptide had characteristics of PP1 and contained a 15 amino acid sequence determined by N-terminal peptide sequence analysis of PP1. The sequence of PP1 was highly repetitive with four 200 amino acid sequence domains containing structural motifs in common with cysteine proteinase inhibitors. Expression of the PP1 gene was detected in roots, hypocotyls, cotyledons, stems, and leaves of pumpkin plants. PP1 and its mRNA accumulated in pumpkin hypocotyls during the period of rapid hypocotyl elongation after which mRNA levels declined, while protein levels remained elevated. PP1 was immunolocalized in slime plugs and P-protein bodies in sieve elements of the phloem. Occasionally, PP1 was detected in companion cells. PP1 mRNA was localized by in situ hybridization in companion cells at early stages of vascular differentiation. The developmental accumulation and localization of PP1 and its mRNA paralleled the phloem lactin, further suggesting an interaction between these phloem-specific proteins.

Nonparametric statistical modeling of binary star separations

NASA Technical Reports Server (NTRS)

Heacox, William D.; Gathright, John

1994-01-01

We develop a comprehensive statistical model for the distribution of observed separations in binary star systems, in terms of distributions of orbital elements, projection effects, and distances to systems. We use this model to derive several diagnostics for estimating the completeness of imaging searches for stellar companions, and the underlying stellar multiplicities. In application to recent imaging searches for low-luminosity companions to nearby M dwarf stars, and for companions to young stars in nearby star-forming regions, our analyses reveal substantial uncertainty in estimates of stellar multiplicity. For binary stars with late-type dwarf companions, semimajor axes appear to be distributed approximately as a(exp -1) for values ranging from about one to several thousand astronomical units. About one-quarter of the companions to field F and G dwarf stars have semimajor axes less than 1 AU, and about 15% lie beyond 1000 AU. The geometric efficiency (fraction of companions imaged onto the detector) of imaging searches is nearly independent of distances to program stars and orbital eccentricities, and varies only slowly with detector spatial limitations.

An FDA Perspective on the Regulatory Implications of Complex Signatures to Predict Response to Targeted Therapies

PubMed Central

Beaver, Julia A.; Tzou, Abraham; Blumenthal, Gideon M.; McKee, Amy E.; Kim, Geoffrey; Pazdur, Richard; Philip, Reena

2016-01-01

As technologies evolve, and diagnostics move from detection of single biomarkers toward complex signatures, an increase in the clinical use and regulatory submission of complex signatures is anticipated. However, to date, no complex signatures have been approved as companion diagnostics. In this article, we will describe the potential benefit of complex signatures and their unique regulatory challenges including analytical performance validation, complex signature simulation, and clinical performance evaluation. We also will review the potential regulatory pathways for clearance, approval, or acceptance of complex signatures by the U.S. Food and Drug Administration (FDA). These regulatory pathways include regulations applicable to in vitro diagnostic devices, including companion diagnostic devices, the potential for labeling as a complementary diagnostic, and the biomarker qualification program. PMID:27993967

Accretion of chemically fractionated material on a wide binary with a blue straggler

NASA Astrophysics Data System (ADS)

Desidera, S.; Gratton, R. G.; Lucatello, S.; Endl, M.; Udry, S.

2007-02-01

Context: The components of the wide binary HIP 64030 = HD 113984 show a large (about 0.25 dex) iron content difference (Desidera et al. 2006). The positions of the components on the color magnitude diagram suggest that the primary is a blue straggler. Aims: We studied the abundance difference of several elements besides iron, and we searched for stellar and substellar companions around the components to unveil the origin of the observed iron difference. Methods: A line-by-line differential abundance analysis for several elements was performed for iron, while suitable spectral synthesis was performed for C, N, and Li. High precision radial velocities obtained with the iodine cell were combined with available literature data. Results: The analysis of additional elements shows that the abundance difference for the elements studied increases with increasing condensation temperature, suggesting that accretion of chemically fractionated material might have occurred in the system. Alteration of C and N likely due to CNO processing is also observed. We also show that the primary is a spectroscopic binary with a period of 445 days and moderate eccentricity. The minimum mass of the companion is 0.17~M⊙. Conclusions: .Two scenarios were explored to explain the observed abundance pattern. In the first, all abundance anomalies arise on the blue straggler. If this is the case, the dust-gas separation may have been occurred in a circumbinary disk around the blue straggler and its expected white dwarf companion, as observed in several RV Tauri and post AGB binaries. In the second scenario, accretion of dust-rich material occurred on the secondary. This would also explain the anomalous carbon isotopic ratio of the secondary. Such a scenario requires that a substantial amount of mass lost by the central binary has been accreted by the wide component. Further studies to compare the two scenarios are proposed. Based on observations collected at the European Southern Observatory, Chile, using FEROS spectrograph (proposal ID: 70.D-0081), on observations made with the Italian Telescopio Nazionale Galileo (TNG) operated on the island of La Palma by the Fundacion Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias, and on observations made at McDonald Observatory.

Lost in Transit: Long-Distance Trafficking and Phloem Unloading of Protein Signals in Arabidopsis Homografts[OPEN

PubMed Central

Gustin, Marie-Paule; Molnar, Attila; Oparka, Karl J.

2016-01-01

In addition to moving sugars and nutrients, the phloem transports many macromolecules. While grafting and aphid stylectomy experiments have identified many macromolecules that move in the phloem, the functional significance of phloem transport of these remains unclear. To gain insight into protein trafficking, we micrografted Arabidopsis thaliana scions expressing GFP-tagged chloroplast transit peptides under the 35S promoter onto nontransgenic rootstocks. We found that plastids in the root tip became fluorescent 10 d after grafting. We obtained identical results with the companion cell-specific promoter SUC2 and with signals that target proteins to peroxisomes, actin, and the nucleus. We were unable to detect the respective mRNAs in the rootstock, indicating extensive movement of proteins in the phloem. Outward movement from the root protophloem was restricted to the pericycle-endodermis boundary, identifying plasmodesmata at this interface as control points in the exchange of macromolecules between stele and cortex. Intriguingly, signals directing proteins to the endoplasmic reticulum and Golgi apparatus from membrane-bound ribosomes were not translocated to the root. It appears that many organelle-targeting sequences are insufficient to prevent the loss of their proteins into the translocation stream. Thus, nonspecific loss of proteins from companion cells to sieve elements may explain the plethora of macromolecules identified in phloem sap. PMID:27600534

Methicillin-resistant Staphylococcus aureus among animals: current overview.

PubMed

Aires-de-Sousa, M

2017-06-01

Currently, methicillin-resistant Staphylococcus aureus (MRSA) is a universal threat. After being well established in the healthcare setting, it has emerged in the community among people with no risk factors for MRSA acquisition, therefore imposing a new threat. The subsequent detection of MRSA colonizing or infecting animals as well as in food of animal origin was of major concern, revealing new reservoirs for MRSA. The major MRSA clonal lineages circulating in the different settings, i.e. in hospitals, in the community and among animals, are described here, differentiating between clones colonizing companion and food-chain animals. Particular attention is given to the widely spread livestock-associated MRSA clonal complex (CC) 398, which is mainly associated with professional exposure but may be of high pathogenicity. The recent detection of a mecA homologue, designated mecC, with a wide geographical distribution in Europe, and including a large diversity of hosts (food-chain, companion and wildlife animals and also detected in water samples) adds to the threat. Domestication as well as globalization of the livestock industry have intensified exchanges between human and animal bacteria. We report here several cases of transmission of MRSA between companion or food-chain animals and humans, as well as some MRSA clones of human origin that have adapted to new animal hosts eventually by losing useless virulence factors or acquiring new mobile genetic elements. Copyright © 2016 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Photoassimilation, Assimilate Translocation and Plasmodesmal Biogenesis in the Source Leaves of Arabidopsis thaliana Grown Under an Increased Atmospheric CO2 Concentration

PubMed Central

Duan, Zhongrui; Homma, Ayumi; Kobayashi, Megumi; Nagata, Noriko; Kaneko, Yasuko; Fujiki, Yuki; Nishida, Ikuo

2014-01-01

Using 18-day-old Arabidopsis thaliana seedlings grown under increased (780 p.p.m., experimental plants) or ambient (390 p.p.m., control plants) CO2 conditions, we evaluated 14CO2 photoassimilation in and translocation from representative source leaves. The total 14CO2 photoassimilation amounts increased in the third leaves of the experimental plants in comparison with that found for the third leaves of the control plants, but the rates were comparable for the first leaves of the two groups. In contrast, translocation of labeled assimilates doubled in the first leaves of the experimental group, whereas translocation was, at best, passively enhanced even though photoassimilation increased in their third leaves. The transcript levels of the companion cell-specific sucrose:H+ symporter gene SUC2 were not significantly affected in the two groups of plants, whereas those of the sucrose effluxer gene SWEET12 and the sieve element-targeted sucrose:H+ symporter gene SUT4 were up-regulated in the experimental plants, suggesting up-regulation of SUT4-dependent apoplastic phloem loading. Compared with SUC2, SUT4 is a minor component that is expressed in companion cells but functions in sieve elements after transfer through plasmodesmata. The number of aniline blue-stained spots for plasmodesma-associated callose in the midrib wall increased in the first leaf of the experimental plants but was comparable in the third leaf between the experimental and control plants. These results suggest that A. thaliana responds to greater than normal concentrations of CO2 differentially in the first and third leaves in regards to photoassimilation, assimilate translocation and plasmodesmal biogenesis. PMID:24406629

[Companion diagnostics in the era of personalized medicine--chairmen's introductory remarks].

PubMed

Fukutsuka, Katsuhiro; Takubo, Takayuki

2014-04-01

Personalized medicine is a medical model that proposes the customization of treatment for individual patients. In this model, diagnostic tests are essential for selecting safer and more efficacious treatments. The term "companion diagnostics" has been used to describe these tests, whereby molecular assays that measure the levels of proteins or specific gene mutations are used to provide a specific therapy for an individual by stratifying the disease status, selecting the proper medication, and tailoring dosages. Examples of companion diagnostics in the field of cancer medicine for molecular targeted therapy include tests for the ALK-fusion gene in non-small cell lung cancer and expression of CCR4 in adult T-cell leukemia. For breast cancer, the expression of HER2 protein is evaluated by immunohistochemistry (IHC), and gene amplification of HER2 is tested by fluorescence in situ hybridization (FISH); both tests consist of pre-analysis, analysis, and post-analysis processes that require quality control to ensure the reliability of the results. This symposium includes: 1) future aspects of companion diagnostics addressing many of the problems that must be overcome, 2) companion diagnostics using FISH focusing on HER2 amplification and ALK alteration, 3) newly developed diagnostic tests using tumor specimens and cell-free DNA in serum, and 4) CCR4 expression detected by IHC and flow cytometry.

WASP-47 and the Origin of Hot Jupiters

NASA Astrophysics Data System (ADS)

Vanderburg, Andrew; Becker, Juliette; Latham, David W.; Adams, Fred; Bryan, Marta; Buchhave, Lars; Haywood, Raphaelle; Khain, Tali; Lopez, Eric; Malavolta, Luca; Mortier, Annelies; HARPS-N Consortium

2018-01-01

WASP-47 b is a transiting hot Jupiter in a system with two additional short-period transiting planets and a long-period outer Jovian companion. WASP-47 b is the only known hot Jupiter with such close-in companions and therefore may hold clues to the origins of hot Jupiter systems. We report on precise radial velocity observations of WASP-47 to measure planet masses and determine their orbits to high precision. Using these improved masses and orbital elements, we perform a dynamical analysis to constrain the inclination of the outer planet, which we find likely orbits near the same plane as the inner transiting system. A similar dynamical analysis for five other hot Jupiter systems with long-period companions around cool host stars (Teff < 6200 K) shows that these outer companions likely also orbit close to the plane of the hot Jupiters. These constraints disfavor hot Jupiter models involving strong dynamical interactions like Kozai-Lidov migration.

Concise Review: Stem Cell Trials Using Companion Animal Disease Models.

PubMed

Hoffman, Andrew M; Dow, Steven W

2016-07-01

Studies to evaluate the therapeutic potential of stem cells in humans would benefit from more realistic animal models. In veterinary medicine, companion animals naturally develop many diseases that resemble human conditions, therefore, representing a novel source of preclinical models. To understand how companion animal disease models are being studied for this purpose, we reviewed the literature between 2008 and 2015 for reports on stem cell therapies in dogs and cats, excluding laboratory animals, induced disease models, cancer, and case reports. Disease models included osteoarthritis, intervertebral disc degeneration, dilated cardiomyopathy, inflammatory bowel diseases, Crohn's fistulas, meningoencephalomyelitis (multiple sclerosis-like), keratoconjunctivitis sicca (Sjogren's syndrome-like), atopic dermatitis, and chronic (end-stage) kidney disease. Stem cells evaluated in these studies included mesenchymal stem-stromal cells (MSC, 17/19 trials), olfactory ensheathing cells (OEC, 1 trial), or neural lineage cells derived from bone marrow MSC (1 trial), and 16/19 studies were performed in dogs. The MSC studies (13/17) used adipose tissue-derived MSC from either allogeneic (8/13) or autologous (5/13) sources. The majority of studies were open label, uncontrolled studies. Endpoints and protocols were feasible, and the stem cell therapies were reportedly safe and elicited beneficial patient responses in all but two of the trials. In conclusion, companion animals with naturally occurring diseases analogous to human conditions can be recruited into clinical trials and provide realistic insight into feasibility, safety, and biologic activity of novel stem cell therapies. However, improvements in the rigor of manufacturing, study design, and regulatory compliance will be needed to better utilize these models. Stem Cells 2016;34:1709-1729. © 2016 AlphaMed Press.

A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics

PubMed Central

Luo, Dee; Smith, James A.; Meadows, Nick A.; Schuh, A.; Manescu, Katie E.; Bure, Kim; Davies, Benjamin; Horne, Rob; Kope, Mike; DiGiusto, David L.; Brindley, David A.

2016-01-01

Rapid innovation in (epi)genetics and biomarker sciences is driving a new drug development and product development pathway, with the personalized medicine era dominated by biologic therapeutics and companion diagnostics. Companion diagnostics (CDx) are tests and assays that detect biomarkers and specific mutations to elucidate disease pathways, stratify patient populations, and target drug therapies. CDx can substantially influence the development and regulatory approval for certain high-risk biologics. However, despite the increasingly important role of companion diagnostics in the realization of personalized medicine, in the USA, there are only 23 Food and Drug Administration (FDA) approved companion diagnostics on the market for 11 unique indications. Personalized medicines have great potential, yet their use is currently constrained. A major factor for this may lie in the increased complexity of the companion diagnostic and corresponding therapeutic development and adoption pathways. Understanding the market dynamics of companion diagnostic/therapeutic (CDx/Rx) pairs is important to further development and adoption of personalized medicine. Therefore, data collected on a variety of factors may highlight incentives or disincentives driving the development of companion diagnostics. Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. The sensitivity of the companion diagnostic was the only factor that significantly correlated with the price of the companion diagnostic. This result indicates that while there is regulatory pressure for the diagnostic and pharmaceutical industry to collaborate and co-develop companion diagnostics for the approval of personalized therapeutics, there seems to be a lack of parallel economic collaboration to incentivize development of companion diagnostics. PMID:26858745

A Quantitative Assessment of Factors Affecting the Technological Development and Adoption of Companion Diagnostics.

PubMed

Luo, Dee; Smith, James A; Meadows, Nick A; Schuh, A; Manescu, Katie E; Bure, Kim; Davies, Benjamin; Horne, Rob; Kope, Mike; DiGiusto, David L; Brindley, David A

2015-01-01

Rapid innovation in (epi)genetics and biomarker sciences is driving a new drug development and product development pathway, with the personalized medicine era dominated by biologic therapeutics and companion diagnostics. Companion diagnostics (CDx) are tests and assays that detect biomarkers and specific mutations to elucidate disease pathways, stratify patient populations, and target drug therapies. CDx can substantially influence the development and regulatory approval for certain high-risk biologics. However, despite the increasingly important role of companion diagnostics in the realization of personalized medicine, in the USA, there are only 23 Food and Drug Administration (FDA) approved companion diagnostics on the market for 11 unique indications. Personalized medicines have great potential, yet their use is currently constrained. A major factor for this may lie in the increased complexity of the companion diagnostic and corresponding therapeutic development and adoption pathways. Understanding the market dynamics of companion diagnostic/therapeutic (CDx/Rx) pairs is important to further development and adoption of personalized medicine. Therefore, data collected on a variety of factors may highlight incentives or disincentives driving the development of companion diagnostics. Statistical analysis for 36 hypotheses resulted in two significant relationships and 34 non-significant relationships. The sensitivity of the companion diagnostic was the only factor that significantly correlated with the price of the companion diagnostic. This result indicates that while there is regulatory pressure for the diagnostic and pharmaceutical industry to collaborate and co-develop companion diagnostics for the approval of personalized therapeutics, there seems to be a lack of parallel economic collaboration to incentivize development of companion diagnostics.

AtSWEET4, a hexose facilitator, mediates sugar transport to axial sinks and affects plant development

PubMed Central

Liu, Xiaozhu; Zhang, Yan; Yang, Chao; Tian, Zhihong; Li, Jianxiong

2016-01-01

Plants transport photoassimilates from source organs to sink tissues through the phloem translocation pathway. In the transport phloem, sugars that escape from the sieve tubes are released into the apoplasmic space between the sieve element/companion cell complex (SE/CC) and phloem parenchyma cells (PPCs) during the process of long-distance transport. The competition for sugar acquisition between SE/CC and adjoining PPCs is mediated by plasma membrane translocators. YFP-tagged AtSWEET4 protein is localized in the plasma membrane, and PromoterAtSWEET4-GUS analysis showed that AtSWEET4 is expressed in the stele of roots and veins of leaves and flowers. Overexpression of AtSWEET4 in Arabidopsis increases plant size and accumulates more glucose and fructose. By contrast, knock-down of AtSWEET4 by RNA-interference leads to small plant size, reduction in glucose and fructose contents, chlorosis in the leaf vein network, and reduction in chlorophyll content in leaves. Yeast assays demonstrated that AtSWEET4 is able to complement both fructose and glucose transport deficiency. Transgenic plants of AtSWEET4 overexpression exhibit higher freezing tolerance and support more growth of bacterium Pseudomonas syringae pv. phaseolicola NPS3121. We conclude that AtSWEET4 plays an important role in mediating sugar transport in axial tissues during plant growth and development. PMID:27102826

The Evolving Role of Companion Diagnostics for Breast Cancer in an Era of Next-Generation Omics.

PubMed

Rosenbaum, Jason N; Weisman, Paul

2017-10-01

A companion diagnostic is a test for a specific biomarker-approved by the United States Food and Drug Administration-qualifying a patient to receive a specific, associated therapy. As interest has grown in precision medicine over the past decade, the principle of companion diagnostics has gained increasing purchase among laboratory professionals, clinicians, regulators, and even patients. The evolution of the biomarkers used to stratify and treat breast cancer illustrates the history of companion diagnostics and provides a lens through which to examine potential challenges. As new targeted therapies and corresponding biomarkers accumulate, algorithms for diagnosis and treatment necessarily become lengthier and more complex. To accommodate future needs of breast cancer patients, the companion diagnostic model will continue to adapt and evolve. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Mini-Review: Limbal Stem Cells Deficiency in Companion Animals: Time to Give Something Back?

PubMed

Sanchez, Rick F; Daniels, Julie T

2016-04-01

Experimental animals have been used extensively in the goal of developing sight-saving therapies for humans. One example is the development of transplantation of cultured limbal epithelial stem cells (LESC) to restore vision following ocular surface injury or disease. With clinical trials of cultured LESC therapy underway in humans and a potential companion animal population suffering from similar diseases, it is perhaps time to give something back. Comparatively to humans, what is known about the healthy limbus and corneal surface physiology of companion animals is still very little. Blinding corneal diseases in animals such as symblepharon in cats with Feline Herpes Virus-1 infections require a basic understanding of the functional companion animal limbus and corneal stem cells. Our understanding of many other vision threatening conditions such as scarring of the cornea post-inflammation with lymphocytic-plasmacytic infiltrate in dogs (aka chronic superficial keratitis) or pigment proliferation with Pigmentary Keratitis of Pugs would benefit from a better understanding of the animal cornea in health and disease. This is also vital when new therapeutic approaches are considered. This review will explore the current challenges and future research directions that will be required to increase our understanding of corneal diseases in animals and consider the potential development and delivery of cultured stem cell therapy to veterinary ocular surface patients.

Validation of an electronic program for pathologist training in the interpretation of a complex companion diagnostic immunohistochemical assay.

PubMed

Dennis, Eslie; Banks, Peter; Murata, Lauren B; Sanchez, Stephanie A; Pennington, Christie; Hockersmith, Linda; Miller, Rachel; Lambe, Jess; Feng, Janine; Kapadia, Monesh; Clements, June; Loftin, Isabell; Singh, Shalini; Das-Gupta, Ashis; Lloyd, William; Bloom, Kenneth

2016-10-01

Companion diagnostics assay interpretation can select patients with the greatest targeted therapy benefits. We present the results from a prospective study demonstrating that pathologists can effectively learn immunohistochemical assay-interpretation skills from digital image-based electronic training (e-training). In this study, e-training was used to train board-certified pathologists to evaluate non-small cell lung carcinoma for eligibility for treatment with onartuzumab, a MET-inhibiting agent. The training program mimicked the live training that was previously validated in clinical trials for onartuzumab. A digital interface was developed for pathologists to review high-resolution, static images of stained slides. Sixty-four pathologists practicing in the United States enrolled while blinded to the type of training. After training, both groups completed a mandatory final test using glass slides. The results indicated both training modalities to be effective. Overall, 80.6% of e-trainees and 72.7% of live trainees achieved passing scores (at least 85%) on the final test. All study participants reported that their training experience was "good" and that they had received sufficient information to determine the adequacy of case slide staining to score each case. This study established that an e-training program conducted under highly controlled conditions can provide pathologists with the skills necessary to interpret a complex assay and that these skills can be equivalent to those achieved with face-to-face training using conventional microscopy. Programs of this type are scalable for global distribution and offer pathologists the potential for readily accessible and robust training in new companion diagnostic assays linked to novel, targeted, adjuvant therapies for cancer patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Complexation of Eu(III), Pb(II), and U(VI) with a Paramecium glycoprotein: Microbial transformation of heavy elements in the aquatic environment.

PubMed

Kozai, Naofumi; Sakamoto, Fuminori; Tanaka, Kazuya; Ohnuki, Toshihiko; Satoh, Takahiro; Kamiya, Tomihiro; Grambow, Bernd

2018-04-01

This study investigated the interaction of inorganic aqueous Eu(III), Pb(II), and U(VI) with Paramecium sp., a representative single-celled protozoan that lives in freshwater. Living and prekilled Paramecium cells were tested. The prekilled cells were killed with a fixative. After 24 h exposure of the cells to inorganic aqueous solutions containing Eu(III) or U(VI), analyses by microparticle-induced X-ray emission with a focused beam (<1 μm) did not detect Eu and U in the living cells, whereas Eu and U were detected in the prekilled cells. Size exclusion chromatography coupled with on-line ultraviolet-visible detection and elemental detection by inductively coupled plasma mass spectrometry of the aqueous phases collected after the living cell experiments revealed that a fraction of the Eu, Pb, and U in the aqueous phase bound to a large (ca. 250 kDa) Paramecium biomolecule and formed a metal-organic complex. The characteristics of the biomolecule were consistent with those of the soluble glycoproteins covering the surfaces of Paramecium cells. These results show that Paramecium cells transform inorganic aqueous Eu, Pb, and U to organic complexes. This paper discusses the relation between this novel complexation and the sorption of these heavy elements on Paramecium cells. Copyright © 2017 Elsevier Ltd. All rights reserved.

A versatile Multisite Gateway-compatible promoter and transgenic line collection for cell type-specific functional genomics in Arabidopsis

PubMed Central

Platre, Matthieu Pierre; Barberon, Marie; Caillieux, Erwann; Colot, Vincent

2016-01-01

Summary Multicellular organisms are composed of many cell types that acquire their specific fate through a precisely controlled pattern of gene expression in time and space dictated in part by cell type-specific promoter activity. Understanding the contribution of highly specialized cell types in the development of a whole organism requires the ability to isolate or analyze different cell types separately. We have characterized and validated a large collection of root cell type-specific promoters and have generated cell type-specific marker lines. These benchmarked promoters can be readily used to evaluate cell type-specific complementation of mutant phenotypes, or to knockdown gene expression using targeted expression of artificial miRNA. We also generated vectors and characterized transgenic lines for cell type-specific induction of gene expression and cell type-specific isolation of nuclei for RNA and chromatin profiling. Vectors and seeds from transgenic Arabidopsis plants will be freely available, and will promote rapid progress in cell type-specific functional genomics. We demonstrate the power of this promoter set for analysis of complex biological processes by investigating the contribution of root cell types in the IRT1-dependent root iron uptake. Our findings revealed the complex spatial expression pattern of IRT1 in both root epidermis and phloem companion cells and the requirement for IRT1 to be expressed in both cell types for proper iron homeostasis. PMID:26662936

Comparing anterior and posterior Hox complex formation reveals guidelines for predicting cis-regulatory elements

PubMed Central

Uhl, Juli D.; Cook, Tiffany A.; Gebelein, Brian

2010-01-01

Hox transcription factors specify numerous cell fates along the anterior-posterior axis by regulating the expression of downstream target genes. While expression analysis has uncovered large numbers of de-regulated genes in cells with altered Hox activity, determining which are direct versus indirect targets has remained a significant challenge. Here, we characterize the DNA binding activity of Hox transcription factor complexes on eight experimentally verified cis-regulatory elements. Hox factors regulate the activity of each element by forming protein complexes with two cofactor proteins, Extradenticle (Exd) and Homothorax (Hth). Using comparative DNA binding assays, we found that a number of flexible arrangements of Hox, Exd, and Hth binding sites mediate cooperative transcription factor complexes. Moreover, analysis of a Distal-less regulatory element (DMXR) that is repressed by abdominal Hox factors revealed that suboptimal binding sites can be combined to form high affinity transcription complexes. Lastly, we determined that the anterior Hox factors are more dependent upon Exd and Hth for complex formation than posterior Hox factors. Based upon these findings, we suggest a general set of guidelines to serve as a basis for designing bioinformatics algorithms aimed at identifying Hox regulatory elements using the wealth of recently sequenced genomes. PMID:20398649

[Ultrastructural observation related to cell-to-cell movement and long-distance systemic transport on the hosts infected with BBWV 2].

PubMed

Hong, Jian; Wang, Wei-Bing; Zhou, Xue-Ping; Hu, Dong-Wei

2006-06-01

The alteration of ultrastructure in Pisum sativum and Vicia faba leaf cells infected with B935 isolate of BBWV 2 were investigated by electron microscopy, immunogold-labeling technique. The results showed that the membranous proliferation, virus-formed crystals and tubular structures were found in leaf cells of two hosts. At early stages of infection, the tubules containing virus-like particles associate with plasmodesmata in mesophyll cell. Immunogold particles anti-BBWV 2 were localized to the plasmodesmata modified by tubules passing through them. The membranous proliferation and virus-formed tubules were also found in the parenchyma cells, companion cells and transfer cells of vascular bundle. Some virus-like particles located within sieve tube can be labeled immunogold particles anti-BBWV 2. These suggest that BBWV 2, similar CPMV, produce tubules extending into the plasmodesmata. Virions assembled in the cytoplasm are escorted to the tubular structures through interactions with their MP and are then transported to the adjacent cell. Many 160 nm in diameter virus-formed tubules in the cytoplasm, as a special aggregate, not directly relate to cell-to-cell movement; Intact virions are long-distance sustemic transported possibly through sieve elements.

The companion dog as a model for human aging and mortality.

PubMed

Hoffman, Jessica M; Creevy, Kate E; Franks, Alexander; O'Neill, Dan G; Promislow, Daniel E L

2018-06-01

Around the world, human populations have experienced large increases in average lifespan over the last 150 years, and while individuals are living longer, they are spending more years of life with multiple chronic morbidities. Researchers have used numerous laboratory animal models to understand the biological and environmental factors that influence aging, morbidity, and longevity. However, the most commonly studied animal species, laboratory mice and rats, do not experience environmental conditions similar to those to which humans are exposed, nor do we often diagnose them with many of the naturally occurring pathologies seen in humans. Recently, the companion dog has been proposed as a powerful model to better understand the genetic and environmental determinants of morbidity and mortality in humans. However, it is not known to what extent the age-related dynamics of morbidity, comorbidity, and mortality are shared between humans and dogs. Here, we present the first large-scale comparison of human and canine patterns of age-specific morbidity and mortality. We find that many chronic conditions that commonly occur in human populations (obesity, arthritis, hypothyroidism, and diabetes), and which are associated with comorbidities, are also associated with similarly high levels of comorbidity in companion dogs. We also find significant similarities in the effect of age on disease risk in humans and dogs, with neoplastic, congenital, and metabolic causes of death showing similar age trajectories between the two species. Overall, our study suggests that the companion dog may be an ideal translational model to study the many complex facets of human morbidity and mortality. © 2018 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Coronal Element Abundances of the Post-Common Envelope Binary V471 Tauri with ASCA

NASA Technical Reports Server (NTRS)

Still, Martin; Hussain, Gaitee; White, Nicholas E. (Technical Monitor)

2002-01-01

We report on ASCA observations of the coronally active companion star in the post-common envelope binary V471 Tau. While it would be prudent to check the following results with grating spectroscopy, we find that a single-temperature plasma model does not fit the data. Two temperature models with variable abundances indicate that Fe is underabundant compared to the Hyades photospheric mean, whereas, the high first ionization potential element Ne is overabundant. This is indicative of the inverse first ionization effect, believed to result from the fractionation of ionized material by the magnetic field in the upper atmosphere of the star. Evolutionary calculations indicate that there should be no peculiar abundances on the companion star resulting from the common envelope epoch. Indeed, we find no evidence for peculiar abundances, although uncertainties are high.

Chemical Evolution of Binary Stars

NASA Astrophysics Data System (ADS)

Izzard, R. G.

2013-02-01

Energy generation by nuclear fusion is the fundamental process that prevents stars from collapsing under their own gravity. Fusion in the core of a star converts hydrogen to heavier elements from helium to uranium. The signature of this nucleosynthesis is often visible in a single star only for a very short time, for example while the star is a red giant or, in massive stars, when it explodes. Contrarily, in a binary system nuclear-processed matter can captured by a secondary star which remains chemically polluted long after its more massive companion star has evolved and died. By probing old, low-mass stars we gain vital insight into the complex nucleosynthesis that occurred when our Galaxy was much younger than it is today. Stellar evolution itself is also affected by the presence of a companion star. Thermonuclear novae and type Ia supernovae result from mass transfer in binary stars, but big questions still surround the nature of their progenitors. Stars may even merge and one of the challenges for the future of stellar astrophysics is to quantitatively understand what happens in such extreme systems. Binary stars offer unique insights into stellar, galactic and extragalactic astrophysics through their plethora of exciting phenomena. Understanding the chemical evolution of binary stars is thus of high priority in modern astrophysics.

Galactoglucomannan oligosaccharides are assumed to affect tracheary element formation via interaction with auxin in Zinnia xylogenic cell culture.

PubMed

Kákošová, Anna; Digonnet, Catherine; Goffner, Deborah; Lišková, Desana

2013-04-01

Galactoglucomannan oligosaccharides seem to interact with auxin in xylogenic cell culture, thus influencing mainly metaxylem-like tracheary element differentiation depending on timing with hormones and the process kinetics. Complex mapping of Zinnia mesophyll cell transdifferentiation into tracheary elements with or without prior cell division was documented after palisade and spongy parenchyma cell immobilization during the first 4 days of culture. Here, we report a positive effect of galactoglucomannan oligosaccharides on cell viability and density and higher metaxylem-like tracheary element formation in xylogenic cell culture. The maximal positive effect was achieved by the simultaneous addition of the oligosaccharides and growth hormones (auxin, cytokinin) to the cell culture medium. Moreover, a large number of metaxylem-like tracheary elements were observed in a low-auxin medium supplemented with oligosaccharides, but not in a low-cytokinin medium, suggesting a close relationship between auxin and the oligosaccharides during tracheary element formation.

Ternary Complex Factors and Cofactors Are Essential for Human T-Cell Leukemia Virus Type 1 Tax Transactivation of the Serum Response Element

PubMed Central

Shuh, Maureen; Derse, David

2000-01-01

The human T-cell leukemia virus type 1 Tax protein activates the expression of cellular immediate early genes controlled by the serum response element (SRE), which contains both the serum response factor (SRF) binding element (CArG box) and the ternary complex factor (TCF) binding element (Ets box). We show that TCF binding is necessary for Tax activation of the SRE and that Tax directly interacts with TCFs in vitro. In addition, Tax interactions with CREB binding protein (CBP) and p300- and CBP-associated factor were found to be essential for Tax activation of SRF-mediated transcription. PMID:11070040

The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein.

PubMed Central

Kristie, T M; LeBowitz, J H; Sharp, P A

1989-01-01

The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions. Images PMID:2556266

The octamer-binding proteins form multi-protein--DNA complexes with the HSV alpha TIF regulatory protein.

PubMed

Kristie, T M; LeBowitz, J H; Sharp, P A

1989-12-20

The herpes simplex virus transactivator, alpha TIF, stimulates transcription of the alpha/immediate early genes via a cis-acting site containing an octamer element and a conserved flanking sequence. The alpha TIF protein, produced in a baculovirus expression system, nucleates the formation of at least two DNA--protein complexes on this regulatory element. Both of these complexes contain the ubiquitous Oct-1 protein, whose POU domain alone is sufficient to allow assembly of the alpha TIF-dependent complexes. A second member of the POU domain family, the lymphoid specific Oct-2 protein, can also be assembled into similar complexes at high concentrations of alpha TIF protein. These complexes contain at least two cellular proteins in addition to Oct-1. One of these proteins is present in both insect and HeLa cells and probably recognizes sequences in the cis element. The second cellular protein, only present in HeLa cells, probably binds by protein-protein interactions.

Magnetic stars with wide depressions in the continuum. 2. The silicon star with a complex field structure HD 27404

NASA Astrophysics Data System (ADS)

Semenko, E. A.; Romanyuk, I. I.; Semenova, E. S.; Moiseeva, A. V.; Kudryavtsev, D. O.; Yakunin, I. A.

2017-10-01

Observations of the chemically peculiar star HD 27404 with the 6-m SAO RAS telescope showed a strong magnetic field with the longitudinal field component varying in a complicated way in the range of -2.5 to 1 kG. Fundamental parameters of the star ( T eff = 11 300 K, log g = 3.9) were estimated analyzing photometric indices in the Geneva and in the Stro¨ mgren-Crawford photometric systems. We detected weak radial velocity variations which can be due to the presence of a close star companion or chemical spots in the photosphere. Rapid estimation of the key chemical element abundance allows us to refer HD 27404 to a SiCr or Si+ chemically peculiar A0-B9 star.

Rating Apathy in Huntington’s Disease: Patients and Companions Agree.

PubMed

Mason, Sarah; Barker, Roger A

2015-01-01

Apathy is a common feature of Huntington’s disease (HD), even from early disease. However, patients are believed to lack insight into their own apathy and therefore clinicians and/or companions are relied upon to estimate the extent of a patient’s apathy. In addition, the evolution of apathy over time in HD has not been unequivocally established. OBJECTIVEs: The purpose of this study was to determine whether HD patient’s self-rated apathy scores were consistent with the scores given by companions who were also asked to rate the patients apathy. Furthermore, the clinical correlates of apathy and its stability over time were examined for both self-rated and companion-rated scores. METHODs: Apathy was measured in a large cross-sectional population of HD patients ranging from early to late stage disease (n = 106) using the Apathy Evaluation Scale; a subgroup of whom were followed longitudinally (n = 62) on average 18.7 (1.2 SD) months later. Comparisons were made between self-rated and companion-rated apathy and the relationship between apathy and motor, cognitive and functional performance was explored. Analysis of the cross-sectional data revealed that self-rated and companion-rated apathy were highly correlated, establishing the validity of using self-rated instead of, or in combination with, companion-rated assessments of apathy in future studies. Both self-rated and companion-rated scores had a relationship with motor and functional impairment, but had a complex relationship with cognition. The results of the longitudinal comparison revealed that apathy did not change over time in this cohort.CONCLUSIONs: Apathy can be equally well assessed by either patients or companions and does not change significantly over an18 month period. These findings have implications in the design of studies looking at treating this important aspect of HD.

TAP 1: A Finite Element Program for Steady-State Thermal Analysis of Convectively Cooled Structures

NASA Technical Reports Server (NTRS)

Thornton, E. A.

1976-01-01

The program has a finite element library of six elements: two conduction/convection elements to model heat transfer in a solid, two convection elements to model heat transfer in a fluid, and two integrated conduction/convection elements to represent combined heat transfer in tubular and plate/fin fluid passages. Nonlinear thermal analysis due to temperature dependent thermal parameters is performed using the Newton-Raphson iteration method. Program output includes nodal temperatures and element heat fluxes. Pressure drops in fluid passages may be computed as an option. A companion plotting program for displaying the finite element model and predicted temperature distributions is presented. User instructions and sample problems are presented in appendixes.

Secure, Network-Centric Operations of a Space-Based Asset: Cisco Router in Low Earth Orbit (CLEO) and Virtual Mission Operations Center (VMOC)

NASA Technical Reports Server (NTRS)

Ivancic, William; Stewart, Dave; Shell, Dan; Wood, Lloyd; Paulsen, Phil; Jackson, Chris; Hodgson, Dave; Notham, James; Bean, Neville; Miller, Eric

2005-01-01

This report documents the design of network infrastructure to support operations demonstrating the concept of network-centric operations and command and control of space-based assets. These demonstrations showcase major elements of the Transformal Communication Architecture (TCA), using Internet Protocol (IP) technology. These demonstrations also rely on IP technology to perform the functions outlined in the Consultative Committee for Space Data Systems (CCSDS) Space Link Extension (SLE) document. A key element of these demonstrations was the ability to securely use networks and infrastructure owned and/or controlled by various parties. This is a sanitized technical report for public release. There is a companion report available to a limited audience. The companion report contains detailed networking addresses and other sensitive material and is available directly from William Ivancic at Glenn Research Center.

Multi-epoch VLTI-PIONIER imaging of the supergiant V766 Cen

NASA Astrophysics Data System (ADS)

Wittkowski, M.; Abellán, F. J.; Arroyo-Torres, B.; Chiavassa, A.; Guirado, J. C.; Marcaide, J. M.; Alberdi, A.; de Wit, W. J.; Hofmann, K.-H.; Meilland, A.; Millour, F.; Mohamed, S.; Sanchez-Bermudez, J.

2017-09-01

Context. The star V766 Cen (=HR 5171A) was originally classified as a yellow hypergiant but lately found to more likely be a 27-36 M⊙ red supergiant (RSG). Recent observations indicated a close eclipsing companion in the contact or common-envelope phase. Aims: Here, we aim at imaging observations of V766 Cen to confirm the presence of the close companion. Methods: We used near-infrared H-band aperture synthesis imaging at three epochs in 2014, 2016, and 2017, employing the PIONIER instrument at the Very Large Telescope Interferometer (VLTI). Results: The visibility data indicate a mean Rosseland angular diameter of 4.1 ± 0.8 mas, corresponding to a radius of 1575 ± 400 R⊙. The data show an extended shell (MOLsphere) of about 2.5 times the Rosseland diameter, which contributes about 30% of the H-band flux. The reconstructed images at the 2014 epoch show a complex elongated structure within the photospheric disk with a contrast of about 10%. The second and third epochs show qualitatively and quantitatively different structures with a single very bright and narrow feature and high contrasts of 20-30%. This feature is located toward the south-western limb of the photospheric stellar disk. We estimate an angular size of the feature of 1.7 ± 0.3 mas, corresponding to a radius of 650 ± 150 R⊙, and giving a radius ratio of 0.42+0.35-0.10 compared to the primary stellar disk. Conclusions: We interpret the images at the 2016 and 2017 epochs as showing the close companion, or a common envelope toward the companion, in front of the primary. At the 2014 epoch, the close companion is behind the primary and not visible. Instead, the structure and contrast at the 2014 epoch are typical of a single RSG harboring giant photospheric convection cells. The companion is most likely a cool giant or supergiant star with a mass of 5+15-3 M⊙. Based on observations made with the VLT Interferometer at Paranal Observatory under programme IDs 092.D-0096, 092.C-0312, and 097.D-0286.Olivier Chesneau was PI of the program 092.D-0096. He unfortunately passed away before seeing the results coming out of it. This Letter may serve as a posthumous tribute to his inspiring work on this source.

Organizational and leadership perceptions assessment: opportunities and challenges using the Baldrige companion surveys.

PubMed

Colombo, Lisa M; Perla, Rocco J; Carifio, James; Bernhardt, Jean M; Slayton, Val W

2011-01-01

Combining the use of employee perception surveys with sound analytical techniques and models is critical to capturing high quality data from which effective decisions can be made in complex healthcare settings. This study used the Baldrige Award companion surveys with an analysis of variance (ANOVA) framework to identify discordant perceptions of hospital staff and leadership in the areas of customer focus, knowledge management, and results that were significant at the 0.05 and 0.01 levels. Senior leaders in the organization found the ANOVA framework helpful as they interpreted results from the Baldrige companion surveys and planned future improvement activities. During the execution of our study a number of difficulties and challenges arose that are not uncommon to survey administration in smaller settings, such as community hospitals, or in larger hospital settings with no research staff or research staff with relevant psychometric expertise. Our experience suggests that the Baldrige companion survey process would be enhanced by providing organizations with general guidance and protocols for optimal survey administration and data analysis. The purpose of this article is to outline the ANOVA model we used with the Baldrige companion surveys and to provide guidance related to the administration and analysis of these companion surveys for those that use them. © 2010 National Association for Healthcare Quality.

Characterization of AgMaT2, a Plasma Membrane Mannitol Transporter from Celery, Expressed in Phloem Cells, Including Phloem Parenchyma Cells[OA

PubMed Central

Juchaux-Cachau, Marjorie; Landouar-Arsivaud, Lucie; Pichaut, Jean-Philippe; Campion, Claire; Porcheron, Benoit; Jeauffre, Julien; Noiraud-Romy, Nathalie; Simoneau, Philippe; Maurousset, Laurence; Lemoine, Rémi

2007-01-01

A second mannitol transporter, AgMaT2, was identified in celery (Apium graveolens L. var. dulce), a species that synthesizes and transports mannitol. This transporter was successfully expressed in two different heterologous expression systems: baker's yeast (Saccharomyces cerevisiae) cells and tobacco (Nicotiana tabacum) plants (a non-mannitol-producing species). Data indicated that AgMaT2 works as an H+/mannitol cotransporter with a weak selectivity toward other polyol molecules. When expressed in tobacco, AgMaT2 decreased the sensitivity to the mannitol-secreting pathogenic fungi Alternaria longipes, suggesting a role for polyol transporters in defense mechanisms. In celery, in situ hybridization showed that AgMaT2 was expressed in the phloem of leaflets, petioles from young and mature leaves, floral stems, and roots. In the phloem of petioles and leaflets, AgMaT2, as localized with specific antibodies, was present in the plasma membrane of three ontologically related cell types: sieve elements, companion cells, and phloem parenchyma cells. These new data are discussed in relation to the physiological role of AgMaT2 in regulating mannitol fluxes in celery petioles. PMID:17631523

Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells.

PubMed

Bryniarski, Krzysztof; Ptak, Wlodzimierz; Martin, Emilia; Nazimek, Katarzyna; Szczepanik, Marian; Sanak, Marek; Askenase, Philip W

2015-01-01

Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases.

Free Extracellular miRNA Functionally Targets Cells by Transfecting Exosomes from Their Companion Cells

PubMed Central

Bryniarski, Krzysztof; Ptak, Wlodzimierz; Martin, Emilia; Nazimek, Katarzyna; Szczepanik, Marian; Sanak, Marek; Askenase, Philip W.

2015-01-01

Lymph node and spleen cells of mice doubly immunized by epicutaneous and intravenous hapten application produce a suppressive component that inhibits the action of the effector T cells that mediate contact sensitivity reactions. We recently re-investigated this phenomenon in an immunological system. CD8+ T lymphocyte-derived exosomes transferred suppressive miR-150 to the effector T cells antigen-specifically due to exosome surface coat of antibody light chains made by B1a lymphocytes. Extracellular RNA (exRNA) is protected from plasma RNases by carriage in exosomes or by chaperones. Exosome transfer of functional RNA to target cells is well described, whereas the mechanism of transfer of exRNA free of exosomes remains unclear. In the current study we describe extracellular miR-150, extracted from exosomes, yet still able to mediate antigen-specific suppression. We have determined that this was due to miR-150 association with antibody-coated exosomes produced by B1a cell companions of the effector T cells, which resulted in antigen-specific suppression of their function. Thus functional cell targeting by free exRNA can proceed by transfecting companion cell exosomes that then transfer RNA cargo to the acceptor cells. This contrasts with the classical view on release of RNA-containing exosomes from the multivesicular bodies for subsequent intercellular targeting. This new alternate pathway for transfer of exRNA between cells has distinct biological and immunological significance, and since most human blood exRNA is not in exosomes may be relevant to evaluation and treatment of diseases. PMID:25923429

[Companion diagnostics "POTELIGEO TEST IHC/FCM" used with "POTELIGEO" (mogamulizumab) for adult T-cell leukemia-lymphoma (ATL) treatment].

PubMed

Goami, Takeshi

2014-05-01

Personalized medicine offers the best treatment for individual patients, it is important for an IVD manufacturer to develop companion diagnostics in parallel with the development of new drugs through close cooperation with drug companies, and supply diagnostics companies with new drugs for physicians and patients. We received approval for a premarket approval application (PMA) for two in vitro diagnostic ("IVD") reagents, POTELIGEO TEST IHC and POTELIGEO TEST FCM ("POTELIGEO TEST"), in March 2012, and subsequently launched POTELIGEO TEST in May 2012. POTELIGEO TEST is a companion diagnostic used with POTELIGEO for which Kyowa Hakko Kirin has a new drug application (NDA) that was approved in March 2012, and is designed to help physicians identify appropriate subpopulations of adult T-cell leukemia-lymphoma(ATL) patients who are most likely to respond to POTELIGEO 20 mg (mogamulizumab) Injection ("POTELIGEO").

Reducing Neuronal Networks to Discrete Dynamics

PubMed Central

Terman, David; Ahn, Sungwoo; Wang, Xueying; Just, Winfried

2008-01-01

We consider a general class of purely inhibitory and excitatory-inhibitory neuronal networks, with a general class of network architectures, and characterize the complex firing patterns that emerge. Our strategy for studying these networks is to first reduce them to a discrete model. In the discrete model, each neuron is represented as a finite number of states and there are rules for how a neuron transitions from one state to another. In this paper, we rigorously demonstrate that the continuous neuronal model can be reduced to the discrete model if the intrinsic and synaptic properties of the cells are chosen appropriately. In a companion paper [1], we analyze the discrete model. PMID:18443649

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van Dyk, Schuyler D.; De Mink, Selma E.; Zapartas, Emmanouil

Core-collapse supernovae (SNe), which mark the deaths of massive stars, are among the most powerful explosions in the universe and are responsible, e.g., for a predominant synthesis of chemical elements in their host galaxies. The majority of massive stars are thought to be born in close binary systems. To date, putative binary companions to the progenitors of SNe may have been detected in only two cases, SNe 1993J and 2011dh. We report on the search for a companion of the progenitor of the Type Ic SN 1994I, long considered to have been the result of binary interaction. Twenty years aftermore » explosion, we used the Hubble Space Telescope to observe the SN site in the ultraviolet (F275W and F336W bands), resulting in deep upper limits on the expected companion: F275W > 26.1 mag and F336W > 24.7 mag. These allow us to exclude the presence of a main sequence companion with a mass ≳10 M{sub ⊙}. Through comparison with theoretical simulations of possible progenitor populations, we show that the upper limits to a companion detection exclude interacting binaries with semi-conservative (late Case A or early Case B) mass transfer. These limits tend to favor systems with non-conservative, late Case B mass transfer with intermediate initial orbital periods and mass ratios. The most likely mass range for a putative main sequence companion would be ∼5–12 M{sub ⊙}, the upper end of which corresponds to the inferred upper detection limit.« less

By-product metals are technologically essential but have problematic supply

PubMed Central

Nassar, N. T.; Graedel, T. E.; Harper, E. M.

2015-01-01

The growth in technological innovation that has occurred over the past decades has, in part, been possible because an increasing number of metals of the periodic table are used to perform specialized functions. However, there have been increasing concerns regarding the reliability of supply of some of these metals. A main contributor to these concerns is the fact that many of these metals are recovered only as by-products from a limited number of geopolitically concentrated ore deposits, rendering their supplies unable to respond to rapid changes in demand. Companionality is the degree to which a metal is obtained largely or entirely as a by-product of one or more host metals from geologic ores. The dependence of companion metal availability on the production of the host metals introduces a new facet of supply risk to modern technology. We evaluated companionality for 62 different metals and metalloids, and show that 61% (38 of 62) have companionality greater than 50%. Eighteen of the 38—including such technologically essential elements as germanium, terbium, and dysprosium—are further characterized as having geopolitically concentrated production and extremely low rates of end-of-life recycling. It is this subset of companion metals—vital in current technologies such as electronics, solar energy, medical imaging, energy-efficient lighting, and other state-of-the-art products—that may be at the greatest risk of supply constraints in the coming decades. PMID:26601159

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana

PubMed Central

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T. T.; McCurdy, David W.

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans-differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018, as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall ingrowth deposition in PP TCs. PMID:29599795

Transcript Profiling Identifies NAC-Domain Genes Involved in Regulating Wall Ingrowth Deposition in Phloem Parenchyma Transfer Cells of Arabidopsis thaliana.

PubMed

Wu, Yuzhou; Hou, Jiexi; Yu, Fen; Nguyen, Suong T T; McCurdy, David W

2018-01-01

Transfer cells (TCs) play important roles in facilitating enhanced rates of nutrient transport at key apoplasmic/symplasmic junctions along the nutrient acquisition and transport pathways in plants. TCs achieve this capacity by developing elaborate wall ingrowth networks which serve to increase plasma membrane surface area thus increasing the cell's surface area-to-volume ratio to achieve increased flux of nutrients across the plasma membrane. Phloem parenchyma (PP) cells of Arabidopsis leaf veins trans -differentiate to become PP TCs which likely function in a two-step phloem loading mechanism by facilitating unloading of photoassimilates into the apoplasm for subsequent energy-dependent uptake into the sieve element/companion cell (SE/CC) complex. We are using PP TCs in Arabidopsis as a genetic model to identify transcription factors involved in coordinating deposition of the wall ingrowth network. Confocal imaging of pseudo-Schiff propidium iodide-stained tissue revealed different profiles of temporal development of wall ingrowth deposition across maturing cotyledons and juvenile leaves, and a basipetal gradient of deposition across mature adult leaves. RNA-Seq analysis was undertaken to identify differentially expressed genes common to these three different profiles of wall ingrowth deposition. This analysis identified 68 transcription factors up-regulated two-fold or more in at least two of the three experimental comparisons, with six of these transcription factors belonging to Clade III of the NAC-domain family. Phenotypic analysis of these NAC genes using insertional mutants revealed significant reductions in levels of wall ingrowth deposition, particularly in a double mutant of NAC056 and NAC018 , as well as compromised sucrose-dependent root growth, indicating impaired capacity for phloem loading. Collectively, these results support the proposition that Clade III members of the NAC-domain family in Arabidopsis play important roles in regulating wall ingrowth deposition in PP TCs.

The iron complex in high mass X-ray binaries

NASA Astrophysics Data System (ADS)

Giménez-García, A.; Torrejón, J. M.; Martínez-Núñez, S.; Rodes-Rocas, J. J.; Bernabéu, G.

2013-05-01

An X-ray binary system consists of a compact object (a white dwarf, a neutron star or a black hole) accreting material from an optical companion star. The spectral type of the optical component strongly affects the mass transfer to the compact object. This is the reason why X-ray binary systems are usually divided in High Mass X-ray Binaries (companion O or B type, denoted HMXB) and Low Mass X-ray Binaries (companion type A or later). The HMXB are divided depending on the partner's luminosity class in two main groups: the Supergiant X-ray Binaries (SGXB) and Be X-ray Binaries (BeXB). We introduce the spectral characterization of a sample of 9 High Mass X-ray Binaries in the iron complex (˜ 6-7 keV). This spectral range is a fundamental tool in the study of the surrounding material of these systems. The sources have been divided into three main groups according to their current standard classification: SGXB, BeXB and γ Cassiopeae-like. The purpose of this work is to look for qualitative patterns in the iron complex, around 6-7 keV, in order to discern between current different classes that make up the group of HMXB. We find significant spectral patterns for each of the sets, reflecting differences in accretion physics thereof.

Spectral-element simulations of wave propagation in complex exploration-industry models: Imaging and adjoint tomography

NASA Astrophysics Data System (ADS)

Luo, Y.; Nissen-Meyer, T.; Morency, C.; Tromp, J.

2008-12-01

Seismic imaging in the exploration industry is often based upon ray-theoretical migration techniques (e.g., Kirchhoff) or other ideas which neglect some fraction of the seismic wavefield (e.g., wavefield continuation for acoustic-wave first arrivals) in the inversion process. In a companion paper we discuss the possibility of solving the full physical forward problem (i.e., including visco- and poroelastic, anisotropic media) using the spectral-element method. With such a tool at hand, we can readily apply the adjoint method to tomographic inversions, i.e., iteratively improving an initial 3D background model to fit the data. In the context of this inversion process, we draw connections between kernels in adjoint tomography and basic imaging principles in migration. We show that the images obtained by migration are nothing but particular kinds of adjoint kernels (mainly density kernels). Migration is basically a first step in the iterative inversion process of adjoint tomography. We apply the approach to basic 2D problems involving layered structures, overthrusting faults, topography, salt domes, and poroelastic regions.

Rapamycin toxicity in MIN6 cells and rat and human islets is mediated by the inhibition of mTOR complex 2 (mTORC2).

PubMed

Barlow, A D; Xie, J; Moore, C E; Campbell, S C; Shaw, J A M; Nicholson, M L; Herbert, T P

2012-05-01

Rapamycin (sirolimus) is one of the primary immunosuppressants for islet transplantation. Yet there is evidence that the long-term treatment of islet-transplant patients with rapamycin may be responsible for subsequent loss of islet graft function and viability. Therefore, the primary objective of this study was to elucidate the molecular mechanism of rapamycin toxicity in beta cells. Experiments were performed on isolated rat and human islets of Langerhans and MIN6 cells. The effects of rapamycin and the roles of mammalian target of rapamycin complex 2 (mTORC2)/protein kinase B (PKB) on beta cell signalling, function and viability were investigated using cell viability assays, insulin ELISA assays, kinase assays, western blotting, pharmacological inhibitors, small interfering (si)RNA and through the overproduction of a constitutively active mutant of PKB. Rapamycin treatment of MIN6 cells and islets of Langerhans resulted in a loss of cell function and viability. Although rapamycin acutely inhibited mTOR complex 1 (mTORC1), the toxic effects of rapamycin were more closely correlated to the dissociation and inactivation of mTORC2 and the inhibition of PKB. Indeed, the overproduction of constitutively active PKB protected islets from rapamycin toxicity whereas the inhibition of PKB led to a loss of cell viability. Moreover, the selective inactivation of mTORC2 using siRNA directed towards rapamycin-insensitive companion of target of rapamycin (RICTOR), mimicked the toxic effects of chronic rapamycin treatment. This report provides evidence that rapamycin toxicity is mediated by the inactivation of mTORC2 and the inhibition of PKB and thus reveals the molecular basis of rapamycin toxicity and the essential role of mTORC2 in maintaining beta cell function and survival.

Molecular Pathology and Personalized Medicine: The Dawn of a New Era in Companion Diagnostics-Practical Considerations about Companion Diagnostics for Non-Small-Cell-Lung-Cancer.

PubMed

Plönes, Till; Engel-Riedel, Walburga; Stoelben, Erich; Limmroth, Christina; Schildgen, Oliver; Schildgen, Verena

2016-01-15

Companion diagnostics (CDx) have become a major tool in molecular pathology and assist in therapy decisions in an increasing number of various cancers. Particularly, the developments in lung cancer have been most impressing in the last decade and consequently lung cancer mutation testing and molecular profiling has become a major business of diagnostic laboratories. However, it has become difficult to decide which biomarkers are currently relevant for therapy decisions, as many of the new biomarkers are not yet approved as therapy targets, remain in the status of clinical studies, or still have not left the experimental phase. The current review is focussed on those markers that do have current therapy implications, practical implications arising from the respective companion diagnostics, and thus is focused on daily practice.

Improvement of pea biomass and seed productivity by simultaneous increase of phloem and embryo loading with amino acids.

PubMed

Zhang, Lizhi; Garneau, Matthew G; Majumdar, Rajtilak; Grant, Jan; Tegeder, Mechthild

2015-01-01

The development of sink organs such as fruits and seeds strongly depends on the amount of nitrogen that is moved within the phloem from photosynthetic-active source leaves to the reproductive sinks. In many plant species nitrogen is transported as amino acids. In pea (Pisum sativum L.), source to sink partitioning of amino acids requires at least two active transport events mediated by plasma membrane-localized proteins, and these are: (i) amino acid phloem loading; and (ii) import of amino acids into the seed cotyledons via epidermal transfer cells. As each of these transport steps might potentially be limiting to efficient nitrogen delivery to the pea embryo, we manipulated both simultaneously. Additional copies of the pea amino acid permease PsAAP1 were introduced into the pea genome and expression of the transporter was targeted to the sieve element-companion cell complexes of the leaf phloem and to the epidermis of the seed cotyledons. The transgenic pea plants showed increased phloem loading and embryo loading of amino acids resulting in improved long distance transport of nitrogen, sink development and seed protein accumulation. Analyses of root and leaf tissues further revealed that genetic manipulation positively affected root nitrogen uptake, as well as primary source and sink metabolism. Overall, the results suggest that amino acid phloem loading exerts regulatory control over pea biomass production and seed yield, and that import of amino acids into the cotyledons limits seed protein levels. © 2014 The Authors The Plant Journal © 2014 John Wiley & Sons Ltd.

Bibliography on Cold Regions Science and Technology. Volume 44, Part 2

DTIC Science & Technology

1990-01-01

eng441404 Lewis icing research tunnel t1 989 , 13p., eng 44-792 um and companion elements in lichen heath near Baker Khodnkov, V. Two-dimensional...elements in lichen heath near Baker Lindstrm, G. Mountains t1 9 88 . p.21-22. chi] 44-631 Lake N.W.T. (1989. 42p.. eng] 44-2114 Modelling extreme...elements in lichen heath sear Baker 10th, Tokyo, Dec. 8-9, 1987 Nixn, J.F. Lake N.W.T. E11989. 482p., engl 44-2114 Proceedings of the NIPR Symposium on

Two MCAT elements of the SM alpha-actin promoter function differentially in SM vs. non-SM cells.

PubMed

Swartz, E A; Johnson, A D; Owens, G K

1998-08-01

Transcriptional activity of the smooth muscle (SM) alpha-actin gene is differentially regulated in SM vs. non-SM cells. Contained within the rat SM alpha-actin promoter are two MCAT motifs, binding sites for transcription enhancer factor 1 (TEF-1) transcriptional factors implicated in the regulation of many muscle-specific genes. Transfections of SM alpha-actin promoter-CAT constructs containing wild-type or mutagenized MCAT elements were performed to evaluate their functional significance. Mutation of the MCAT elements resulted in increased transcriptional activity in SM cells, whereas these mutations either had no effect or decreased activity in L6 myotubes or endothelial cells. High-resolution gel shift assays resolved several complexes of different mobilities that were formed between MCAT oligonucleotides and nuclear extracts from the different cell types, although no single band was unique to SM. Western blot analysis of nuclear extracts with polyclonal antibodies to conserved domains of the TEF-1 gene family revealed multiple reactive bands, some that were similar and others that differed between SM and non-SM. Supershift assays with a polyclonal antibody to the TEF-related protein family demonstrated that TEF-1 or TEF-1-related proteins were contained in the shifted complexes. Results suggest that the MCAT elements may contribute to cell type-specific regulation of the SM alpha-actin gene. However, it remains to be determined whether the differential transcriptional activity of MCAT elements in SM vs. non-SM is due to differences in expression of TEF-1 or TEF-1-related proteins or to unique (cell type specific) combinatorial interactions of the MCAT elements with other cis-elements and trans-factors.

"Community", Semiotic Flows, and Mediated Contribution to Activity

ERIC Educational Resources Information Center

Thorne, Steven L.

2009-01-01

This article begins with an overview and problematization of the term "community" through a brief assessment of its history, diverse uses, core attributes, heterogeneous elements, and collocational companions. Following this, I describe demographics and processes associated with collective engagement in digitally mediated environments. Utilizing…

Twelve years of IUE spectra of the interacting binary VV Cephei

NASA Technical Reports Server (NTRS)

Bauer, W. H.; Stencel, R. E.; Neff, D. H.

1991-01-01

All well-exposed high-resolution IUE spectra obtained of the eclipsing binary system VV Cephei (M2Iabep + B) are examined. High-temperature absorption features attributable to the hot companion were detected, indicating that the companion (or the inner regions of its accretion disk) are not as hot as a B1-B2 star. Doubling of Fe II (UV 1) lines, with an additional narrow component redshifted by about 60 km/sec, occurs only when the B star is behind the plane of the sky containing the M supergiant, suggesting the existence of mass transfer from the red to the blue star. Absorption features from neutral elements weaken dramatically during egress, while those from ionized elements remain at nearly constant strength. During egress from primary eclipse, the Mg II resonance doublet shows asymmetric double-peaked emission indicative of formation in an expanding chromosphere. It is concluded that the outer atmosphere of the M supergiant is highly clumped.

On an algorithmic definition for the components of the minimal cell.

PubMed

Martínez, Octavio; Reyes-Valdés, M Humberto

2018-01-01

Living cells are highly complex systems comprising a multitude of elements that are engaged in the many convoluted processes observed during the cell cycle. However, not all elements and processes are essential for cell survival and reproduction under steady-state environmental conditions. To distinguish between essential from expendable cell components and thus define the 'minimal cell' and the corresponding 'minimal genome', we postulate that the synthesis of all cell elements can be represented as a finite set of binary operators, and within this framework we show that cell elements that depend on their previous existence to be synthesized are those that are essential for cell survival. An algorithm to distinguish essential cell elements is presented and demonstrated within an interactome. Data and functions implementing the algorithm are given as supporting information. We expect that this algorithmic approach will lead to the determination of the complete interactome of the minimal cell, which could then be experimentally validated. The assumptions behind this hypothesis as well as its consequences for experimental and theoretical biology are discussed.

C/O vs. Mg/Si ratios in solar type stars: The HARPS sample

NASA Astrophysics Data System (ADS)

Suárez-Andrés, L.; Israelian, G.; Hernández, J. I. González; Adibekyan, V. Zh.; Delgado Mena, E.; Santos, N. C.; Sousa, S. G.

2018-06-01

Context. Aims: We aim to present a detailed study of the magnesium-to-silicon and carbon-to-oxygen ratios (Mg/Si and C/O) and their importance in determining the mineralogy of planetary companions. Methods: Using 499 solar-like stars from the HARPS sample, we determined C/O and Mg/Si elemental abundance ratios to study the nature of the possible planets formed. We separated the planetary population in low-mass planets (<30 M⊙) and high-mass planets (>30 M⊙) to test for a possible relation with the mass. Results: We find a diversity of mineralogical ratios that reveal the different kinds of planetary systems that can be formed, most of them dissimilar to our solar system. The different values of the Mg/Si and C/O can determine different composition of planets formed. We found that 100% of our planetary sample present C/O < 0.8. 86% of stars with high-mass companions present 0.8 > C/O > 0.4, while 14% present C/O values lower than 0.4. Regarding Mg/Si, all stars with low-mass planetary companion showed values between one and two, while 85% of the high-mass companion sample does. The other 15% showed Mg/Si values below one. No stars with planets were found with Mg/Si > 2. Planet hosts with low-mass companions present C/O and Mg/Si similar to those found in the Sun, whereas stars with high-mass companions have lower C/O. The full Table 1 is only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/614/A84

Symplastic continuity between mesophyll and companion cells in minor veins of mature Cucurbita pepo L. leaves.

PubMed

Turgeon, R; Hepler, P K

1989-08-01

Dye-coupling studies have been undertaken to determine whether plasmodesmata between intermediary cells (companion cells) and bundle-sheath cells in the minor veins of mature Cucurbita pepo L. leaves are open to passage of low-molecular-weight compounds. The abaxial phloem of these veins was exposed by stripping the lower epidermis of the leaf and removing the spongy-mesophyll cells by abrasion. Lucifer yellow, or 6-carboxyfluorescein, were microinjected into intermediary cells by iontophoresis, and dye location was monitored by fluorescence microscopy. Dye spread from one intermediary cell to another and from intermediary cells to bundle-sheath and mesophyll cells. No movement of microinjected dye occurred in some experiments, probably because plasmodesmata closed in response to cell damage incurred during tissue preparation. Most, but not all, minor veins in tissue prepared for microinjections studies are able to accumulate exogenously supplied [(14)C]sucrose. Plasmolysis studies indicate that the solute content of intermediary cells is much higher than that of bundle-sheath cells. In C. pepo, plasmodesmata may provide a route for the selective phloem loading of export sugars.

The Transcriptional Complex Between the BCL2 i-Motif and hnRNP LL Is a Molecular Switch for Control of Gene Expression That Can Be Modulated by Small Molecules

PubMed Central

2015-01-01

In a companion paper (DOI: 10.021/ja410934b) we demonstrate that the C-rich strand of the cis-regulatory element in the BCL2 promoter element is highly dynamic in nature and can form either an i-motif or a flexible hairpin. Under physiological conditions these two secondary DNA structures are found in an equilibrium mixture, which can be shifted by the addition of small molecules that trap out either the i-motif (IMC-48) or the flexible hairpin (IMC-76). In cellular experiments we demonstrate that the addition of these molecules has opposite effects on BCL2 gene expression and furthermore that these effects are antagonistic. In this contribution we have identified a transcriptional factor that recognizes and binds to the BCL2 i-motif to activate transcription. The molecular basis for the recognition of the i-motif by hnRNP LL is determined, and we demonstrate that the protein unfolds the i-motif structure to form a stable single-stranded complex. In subsequent experiments we show that IMC-48 and IMC-76 have opposite, antagonistic effects on the formation of the hnRNP LL–i-motif complex as well as on the transcription factor occupancy at the BCL2 promoter. For the first time we propose that the i-motif acts as a molecular switch that controls gene expression and that small molecules that target the dynamic equilibrium of the i-motif and the flexible hairpin can differentially modulate gene expression. PMID:24559432

Chemical abundances and kinematics of TYC 5619-109-1

NASA Astrophysics Data System (ADS)

Pereira, C. B.; Smith, V. V.; Drake, N. A.; Roig, F.; Hasselquist, S.; Cunha, K.; Jilinski, E.

2017-07-01

Previous determinations of chemical abundances of the metal-poor red giant TYC 5619-109-1, derived via high-resolution near-infrared spectra from the Apache Point Observatory Galactic Evolution Experiment survey, indicate that this star is strongly enriched in the elements N and Al. Here, we obtain and analyse high-resolution optical spectra of TYC 5619-109-1 to verify these large N and Al overabundances and to measure abundances of a wider range of chemical elements. Our analysis confirms the N- and Al-rich nature of this star, and shows that the abundances of the s-process elements are also strongly enhanced, particularly in the heavy second s-process peak elements (Ba, La, Ce, Nd). Lighter s-process elements (Y, Zr) show smaller overabundances, and the ratio of the light-to-heavy s-process elements is consistent with the 13C(α, n)16O neutron source operating in a low-metallicity environment. The lack of Tc I lines and the abundance of Nb compared to Zr indicate that this red giant is probably not a thermally pulsing asymptotic giant branch (TP-AGB) star. Mass transfer from a former s-process-rich TP-AGB companion may produce the observed overabundances, but our radial velocity analysis provides no evidence that TYC 5619-109-1 is a binary with a white dwarf companion. We suggest that TYC 5619-109-1 formed from gas already strongly enriched in s-process elements, as found in many dwarf galaxies and globular clusters. A dynamical analysis reveals that there is only a small probability that TYC 5619-109-1 is an escaped member of a globular cluster, and in this case the most likely candidate would be ω Cen.

Interrelated striated elements in vestibular hair cells of the rat

NASA Technical Reports Server (NTRS)

Ross, M. D.; Bourne, C.

1983-01-01

A series of interrelated striated organelles in types I and II vestibular hair cells of the rat which appear to be less developed in cochlear hair cells have been revealed by unusual fixation procedures, suggesting that contractile elements may play a role in sensory transduction in the inner ear, especially in the vestibular system. Included in the series of interrelated striated elements are the cuticular plate and its basal attachments to the hair cell margins, the connections of the strut array of the kinociliary basal body to the cuticular plate, and striated organelles associated with the plasma membrane and extending below the apical junctional complexes.

SEACAS Theory Manuals: Part III. Finite Element Analysis in Nonlinear Solid Mechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Laursen, T.A.; Attaway, S.W.; Zadoks, R.I.

1999-03-01

This report outlines the application of finite element methodology to large deformation solid mechanics problems, detailing also some of the key technological issues that effective finite element formulations must address. The presentation is organized into three major portions: first, a discussion of finite element discretization from the global point of view, emphasizing the relationship between a virtual work principle and the associated fully discrete system, second, a discussion of finite element technology, emphasizing the important theoretical and practical features associated with an individual finite element; and third, detailed description of specific elements that enjoy widespread use, providing some examples ofmore » the theoretical ideas already described. Descriptions of problem formulation in nonlinear solid mechanics, nonlinear continuum mechanics, and constitutive modeling are given in three companion reports.« less

Micro-macroscopic coupled modeling of batteries and fuel cells. 2: Application to nickel-cadmium and nickel-metal hydride cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gu, W.B.; Wang, C.Y.; Liaw, B.Y.

1998-10-01

The micro-macroscopic coupled model developed in a companion paper is applied to predict the discharge and charge behaviors of nickel-cadmium (Ni-Cd) and nickel-metal hydride (Ni-MH) cells. The model integrates important microscopic phenomena such as proton or hydrogen diffusion and conduction of electrons in active materials into the macroscopic calculations of species and charge transfer. Simulation results for a full Ni-Cd cell and single MH electrode are presented and validated against the pseudo two-dimensional numerical model in the literature. In good agreement with the previous results, the present family of models is computationally more efficient and is particularly suitable for simulationsmore » of complex test conditions, such as the dynamic stress test and pulse charging for electric vehicles. In addition, a mathematical model for full Ni-MH cells is presented and sample simulations are performed for discharge and recharge with oxygen generation and recombination taken into account. These gas reactions represent an important mechanism for battery overcharge in the electric vehicle application.« less

Promoting physical therapists' of research evidence to inform clinical practice: part 1--theoretical foundation, evidence, and description of the PEAK program.

PubMed

Tilson, Julie K; Mickan, Sharon

2014-06-25

There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists' integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura's social cognitive theory and Malcolm Knowles's adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a "Best Practices List" - a list of locally generated, evidence-based, actionable behaviors relevant to the groups' clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program - an educational program designed to promote the use of research evidence to inform physical therapist practice. The four components of the program are described in detail. The companion paper reports the results of a mixed methods feasibility analysis of this complex educational intervention.

Monoclonal antibodies expression improvement in CHO cells by PiggyBac transposition regarding vectors ratios and design.

PubMed

Ahmadi, Samira; Davami, Fatemeh; Davoudi, Noushin; Nematpour, Fatemeh; Ahmadi, Maryam; Ebadat, Saeedeh; Azadmanesh, Kayhan; Barkhordari, Farzaneh; Mahboudi, Fereidoun

2017-01-01

Establishing stable Chinese Hamster Ovary (CHO) cells producing monoclonal antibodies (mAbs) usually pass through the random integration of vectors to the cell genome, which is sensitive to gene silencing. One approach to overcome this issue is to target a highly transcribed region in the genome. Transposons are useful devices to target active parts of genomes, and PiggyBac (PB) transposon can be considered as a good option. In the present study, three PB transposon donor vectors containing both heavy and light chains were constructed, one contained independent expression cassettes while the others utilized either an Internal Ribosome Entry Site (IRES) or 2A element to express mAb. Conventional cell pools were created by transferring donor vectors into the CHO cells, whereas transposon-based cells were generated by transfecting the cells with donor vectors with a companion of a transposase-encoding helper vector, with 1:2.5 helper/donor vectors ratio. To evaluate the influence of helper/donor vectors ratio on expression, the second transposon-based cell pools were generated with 1:5 helper/donor ratio. Expression levels in the transposon-based cells were two to five -folds more than those created by conventional method except for the IRES-mediated ones, in which the observed difference increased more than 100-fold. The results were dependent on both donor vector design and vectors ratios.

Monoclonal antibodies expression improvement in CHO cells by PiggyBac transposition regarding vectors ratios and design

PubMed Central

Ahmadi, Samira; Davami, Fatemeh; Davoudi, Noushin; Nematpour, Fatemeh; Ahmadi, Maryam; Ebadat, Saeedeh; Azadmanesh, Kayhan; Barkhordari, Farzaneh

2017-01-01

Establishing stable Chinese Hamster Ovary (CHO) cells producing monoclonal antibodies (mAbs) usually pass through the random integration of vectors to the cell genome, which is sensitive to gene silencing. One approach to overcome this issue is to target a highly transcribed region in the genome. Transposons are useful devices to target active parts of genomes, and PiggyBac (PB) transposon can be considered as a good option. In the present study, three PB transposon donor vectors containing both heavy and light chains were constructed, one contained independent expression cassettes while the others utilized either an Internal Ribosome Entry Site (IRES) or 2A element to express mAb. Conventional cell pools were created by transferring donor vectors into the CHO cells, whereas transposon-based cells were generated by transfecting the cells with donor vectors with a companion of a transposase-encoding helper vector, with 1:2.5 helper/donor vectors ratio. To evaluate the influence of helper/donor vectors ratio on expression, the second transposon-based cell pools were generated with 1:5 helper/donor ratio. Expression levels in the transposon-based cells were two to five -folds more than those created by conventional method except for the IRES-mediated ones, in which the observed difference increased more than 100-fold. The results were dependent on both donor vector design and vectors ratios. PMID:28662065

A Guide to Program Planning Vol. II.

ERIC Educational Resources Information Center

Allen, Earl, Sr.

This booklet is a simplified guide for program planning and is intended to complement a somewhat lengthier companion booklet on program evaluation. It spells out in outline fashion the basic elements and steps involved in the planning process. Brief sections focus in turn on different phases of the planning process, including problem…

A developmental model of recreation choice behavior

Treesearch

Daniel R. Williams

1985-01-01

Recreation choices are viewed as including, at least implicitly, a selection of an activity, a setting, and a set of companions. With development these three elements become increasingly differentiated from one another. The model is tested by examining the perceived similarities among a set of 15 recreation choices depicted in color slides.

Microarray Analysis of LTR Retrotransposon Silencing Identifies Hdac1 as a Regulator of Retrotransposon Expression in Mouse Embryonic Stem Cells

PubMed Central

Madej, Monika J.; Taggart, Mary; Gautier, Philippe; Garcia-Perez, Jose Luis; Meehan, Richard R.; Adams, Ian R.

2012-01-01

Retrotransposons are highly prevalent in mammalian genomes due to their ability to amplify in pluripotent cells or developing germ cells. Host mechanisms that silence retrotransposons in germ cells and pluripotent cells are important for limiting the accumulation of the repetitive elements in the genome during evolution. However, although silencing of selected individual retrotransposons can be relatively well-studied, many mammalian retrotransposons are seldom analysed and their silencing in germ cells, pluripotent cells or somatic cells remains poorly understood. Here we show, and experimentally verify, that cryptic repetitive element probes present in Illumina and Affymetrix gene expression microarray platforms can accurately and sensitively monitor repetitive element expression data. This computational approach to genome-wide retrotransposon expression has allowed us to identify the histone deacetylase Hdac1 as a component of the retrotransposon silencing machinery in mouse embryonic stem cells, and to determine the retrotransposon targets of Hdac1 in these cells. We also identify retrotransposons that are targets of other retrotransposon silencing mechanisms such as DNA methylation, Eset-mediated histone modification, and Ring1B/Eed-containing polycomb repressive complexes in mouse embryonic stem cells. Furthermore, our computational analysis of retrotransposon silencing suggests that multiple silencing mechanisms are independently targeted to retrotransposons in embryonic stem cells, that different genomic copies of the same retrotransposon can be differentially sensitive to these silencing mechanisms, and helps define retrotransposon sequence elements that are targeted by silencing machineries. Thus repeat annotation of gene expression microarray data suggests that a complex interplay between silencing mechanisms represses retrotransposon loci in germ cells and embryonic stem cells. PMID:22570599

AQUIFEM-SALT; a finite-element model for aquifers containing a seawater interface

USGS Publications Warehouse

Voss, C.I.

1984-01-01

Described are modifications to AQUIFEM, a finite element areal ground-water flow model for aquifer evaluation. The modified model, AQUIFEM-SALT, simulates an aquifer containing a freshwater body that freely floats on seawater. Parts of the freshwater lens may be confined above and below by less permeable units. Theory, code modifications, and model verification are discussed. A modified input data list is included. This report is intended as a companion to the original AQUIFEM documentation. (USGS)

The application of interactive graphics to large time-dependent hydrodynamics problems

NASA Technical Reports Server (NTRS)

Gama-Lobo, F.; Maas, L. D.

1975-01-01

A written companion of a movie entitled "Interactive Graphics at Los Alamos Scientific Laboratory" was presented. While the movie presents the actual graphics terminal and the functions performed on it, the paper attempts to put in perspective the complexity of the application code and the complexity of the interaction that is possible.

The insulin and islet amyloid polypeptide genes contain similar cell-specific promoter elements that bind identical beta-cell nuclear complexes.

PubMed Central

German, M S; Moss, L G; Wang, J; Rutter, W J

1992-01-01

The pancreatic beta cell makes several unique gene products, including insulin, islet amyloid polypeptide (IAPP), and beta-cell-specific glucokinase (beta GK). The functions of isolated portions of the insulin, IAPP, and beta GK promoters were studied by using transient expression and DNA binding assays. A short portion (-247 to -197 bp) of the rat insulin I gene, the FF minienhancer, contains three interacting transcriptional regulatory elements. The FF minienhancer binds at least two nuclear complexes with limited tissue distribution. Sequences similar to that of the FF minienhancer are present in the 5' flanking DNA of the human IAPP and rat beta GK genes and also the rat insulin II and mouse insulin I and II genes. Similar minienhancer constructs from the insulin and IAPP genes function as cell-specific transcriptional regulatory elements and compete for binding of the same nuclear factors, while the beta GK construct competes for protein binding but functions poorly as a minienhancer. These observations suggest that the patterns of expression of the beta-cell-specific genes result in part from sharing the same transcriptional regulators. Images PMID:1549125

Growing Bladder-Cancer Cells In Three-Dimensional Clusters

NASA Technical Reports Server (NTRS)

Spaulding, Glenn F.; Prewett, Tacey L.; Goodwin, Thomas J.

1995-01-01

Artificial growth process helps fill gaps in cancer research. Cell cultures more accurate as models for in vivo studies and as sources of seed cells for in vivo studies. Effected in horizontal rotating bioreactor described in companion article, "Simplified Bioreactor for Growing Mammalian Cells" (MSC-22060). Provides aggregates of cells needed to fill many of gaps.

Control of the synthesis and subcellular targeting of the two GDH genes products in leaves and stems of Nicotiana plumbaginifolia and Arabidopsis thaliana.

PubMed

Fontaine, Jean-Xavier; Saladino, Francesca; Agrimonti, Caterina; Bedu, Magali; Tercé-Laforgue, Thérèse; Tétu, Thierry; Hirel, Bertrand; Restivo, Francesco M; Dubois, Frédéric

2006-03-01

Although the physiological role of the enzyme glutamate dehydrogenase which catalyses in vitro the reversible amination of 2-oxoglutarate to glutamate remains to be elucidated, it is now well established that in higher plants the enzyme preferentially occurs in the mitochondria of phloem companion cells. The Nicotiana plumbaginifolia and Arabidopis thaliana enzyme is encoded by two distinct genes encoding either an alpha- or a beta-subunit. Using antisense plants and mutants impaired in the expression of either of the two genes, we showed that in leaves and stems both the alpha- and beta-subunits are targeted to the mitochondria of the companion cells. In addition, we found in both species that there is a compensatory mechanism up-regulating the expression of the alpha-subunit in the stems when the expression of the beta-subunit is impaired in the leaves, and of the beta-subunit in the leaves when the expression of the alpha-subunit is impaired in the stems. When one of the two genes encoding glutamate dehydrogenase is ectopically expressed, the corresponding protein is targeted to the mitochondria of both leaf and stem parenchyma cells and its production is increased in the companion cells. These results are discussed in relation to the possible signalling and/or physiological function of the enzyme which appears to be coordinated in leaves and stems.

The Oxford Companion to the Earth

NASA Astrophysics Data System (ADS)

Hancock, Paul L.

2001-06-01

Here is a wealth of information on planet Earth, ranging from the heights of the ionsphere down to the red-hot molten core. Written by some 200 expert contributors, and illustrated with over 600 pictures, including 16 pages of color plates, The Oxford Companion to the Earth offers 900 alphabetically arranged entries that cover everything from deserts and wetlands to mountains, caves, glaciers, and coral reefs. There are articles on natural phenomena such as tornadoes and tsunamis, volcanoes and earthquakes, jet streams and weather fronts; on the history of Earth, including the origin of life, Burgess Shale fauna, dinosaurs, and the Ice Ages; on key figures, such as Agassiz, Cuvier, Darwin, and Lamarck; and on such important ecological concerns as acid rain, the ozone layer, industrial waste disposal, and the greenhouse effect. The Companion also examines the great sources of wealth to be found in the Earth, from coal and oil to gold, silver, and diamonds, and many curious land formations, from sinkholes and fiords to yardangs and quicksand. There are brief entries on rock types, from amber to travertine, and extensive essays on cutting-edge aspects of the earth sciences, such as seismology and marine geology. The Companion includes extensive cross-references, suggested further reading, an index, and many useful appendices, with a geological timescale, facts and figures about the Earth, and a table of chemical elements. The Oxford Companion to the Earth is a unique reference work, offering unrivaled coverage of our home planet. Generously illustrated and vividly written, it is a treasure house of information for all lovers of natural history, geology, and ecology, whether professional or amateur.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guo, Zheng; Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, 1838 Guangzhou Dadao Bei, Guangzhou 510515; Zhou, Yuning

Highlights: Black-Right-Pointing-Pointer Rictor associates with FBXW7 to form an E3 complex. Black-Right-Pointing-Pointer Knockdown of rictor decreases ubiquitination of c-Myc and cylin E. Black-Right-Pointing-Pointer Knockdown of rictor increases protein levels of c-Myc and cylin E. Black-Right-Pointing-Pointer Overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Black-Right-Pointing-Pointer Rictor regulation of c-Myc and cyclin E requires FBXW7. -- Abstract: Rictor (Rapamycin-insensitive companion of mTOR) forms a complex with mTOR and phosphorylates and activates Akt. Activation of Akt induces expression of c-Myc and cyclin E, which are overexpressed in colorectal cancer and play an important role in colorectal cancer cell proliferation.more » Here, we show that rictor associates with FBXW7 to form an E3 complex participating in the regulation of c-Myc and cyclin E degradation. The Rictor-FBXW7 complex is biochemically distinct from the previously reported mTORC2 and can be immunoprecipitated independently of mTORC2. Moreover, knocking down of rictor in serum-deprived colorectal cancer cells results in the decreased ubiquitination and increased protein levels of c-Myc and cyclin E while overexpression of rictor induces the degradation of c-Myc and cyclin E proteins. Genetic knockout of FBXW7 blunts the effects of rictor, suggesting that rictor regulation of c-Myc and cyclin E requires FBXW7. Our findings identify rictor as an important component of FBXW7 E3 ligase complex participating in the regulation of c-Myc and cyclin E protein ubiquitination and degradation. Importantly, our results suggest that elevated growth factor signaling may contribute to decrease rictor/FBXW7-mediated ubiquitination of c-Myc and cyclin E, thus leading to accumulation of cyclin E and c-Myc in colorectal cancer cells.« less

Improving the Efficiency and Quality of the Value Assessment Process for Companion Diagnostic Tests: The Companion test Assessment Tool (CAT).

PubMed

Canestaro, William J; Pritchard, Daryl E; Garrison, Louis P; Dubois, Robert; Veenstra, David L

2015-08-01

Companion diagnostic tests (CDTs) have emerged as a vital technology in the effective use of an increasing number of targeted drug therapies. Although CDTs can offer a multitude of potential benefits, assessing their value within a health technology appraisal process can be challenging because of a complex array of factors that influence clinical and economic outcomes. To develop a user-friendly tool to assist managed care and other health care decision makers in screening companion tests and determining whether an intensive technology review is necessary and, if so, where the review should be focused to improve efficiency. First, we conducted a systematic literature review of CDT cost-effectiveness studies to identify value drivers. Second, we conducted key informant interviews with a diverse group of stakeholders to elicit feedback and solicit any additional value drivers and identify desirable attributes for an evidence review tool. A draft tool was developed based on this information that captured value drivers, usability features, and had a particular focus on practical use by nonexperts. Finally, the tool was pilot tested with test developers and managed care evidence evaluators to assess face-validity and usability. The tool was also evaluated using several diverse examples of existing companion diagnostics and refined accordingly. We identified 65 cost-effectiveness studies of companion diagnostic technologies. The following factors were most commonly identified as value drivers from our literature review: clinical validity of testing; efficacy, safety, and cost of baseline and alternative treatments; cost and mortality of health states; and biomarker prevalence and testing cost. Stakeholders identified the following additional factors that they believed influenced the overall value of a companion test: regulatory status, actionability, utility, and market penetration. These factors were used to maximize the efficiency of the evidence review process. Stakeholders also stated that a tool should be easy to use and time efficient. Cognitive interviews with stakeholders led to minor changes in the draft tool to improve usability and relevance. The final tool consisted of 4 sections: (1) eligibility for review (2 questions), (2) prioritization of review (3 questions), (3) clinical review (3 questions), and (4) economic review (5 questions). Although the evaluation of CDTs can be challenging because of limited evidence and the added complexity of incorporating a diagnostic test into drug treatment decisions, using a pragmatic tool to identify tests that do not need extensive evaluation may improve the efficiency and effectiveness of CDT value assessments.

Diffusion and bulk flow in phloem loading: A theoretical analysis of the polymer trap mechanism for sugar transport in plants

NASA Astrophysics Data System (ADS)

Dölger, Julia; Rademaker, Hanna; Liesche, Johannes; Schulz, Alexander; Bohr, Tomas

2014-10-01

Plants create sugar in the mesophyll cells of their leaves by photosynthesis. This sugar, mostly sucrose, has to be loaded via the bundle sheath into the phloem vascular system (the sieve elements), where it is distributed to growing parts of the plant. We analyze the feasibility of a particular loading mechanism, active symplasmic loading, also called the polymer trap mechanism, where sucrose is transformed into heavier sugars, such as raffinose and stachyose, in the intermediary-type companion cells bordering the sieve elements in the minor veins of the phloem. Keeping the heavier sugars from diffusing back requires that the plasmodesmata connecting the bundle sheath with the intermediary cell act as extremely precise filters, which are able to distinguish between molecules that differ by less than 20% in size. In our modeling, we take into account the coupled water and sugar movement across the relevant interfaces, without explicitly considering the chemical reactions transforming the sucrose into the heavier sugars. Based on the available data for plasmodesmata geometry, sugar concentrations, and flux rates, we conclude that this mechanism can in principle function, but that it requires pores of molecular sizes. Comparing with the somewhat uncertain experimental values for sugar export rates, we expect the pores to be only 5%-10% larger than the hydraulic radius of the sucrose molecules. We find that the water flow through the plasmodesmata, which has not been quantified before, contributes only 10%-20% to the sucrose flux into the intermediary cells, while the main part is transported by diffusion. On the other hand, the subsequent sugar translocation into the sieve elements would very likely be carried predominantly by bulk water flow through the plasmodesmata. Thus, in contrast to apoplasmic loaders, all the necessary water for phloem translocation would be supplied in this way with no need for additional water uptake across the plasma membranes of the phloem.

Diffusion and bulk flow in phloem loading: a theoretical analysis of the polymer trap mechanism for sugar transport in plants.

PubMed

Dölger, Julia; Rademaker, Hanna; Liesche, Johannes; Schulz, Alexander; Bohr, Tomas

2014-10-01

Plants create sugar in the mesophyll cells of their leaves by photosynthesis. This sugar, mostly sucrose, has to be loaded via the bundle sheath into the phloem vascular system (the sieve elements), where it is distributed to growing parts of the plant. We analyze the feasibility of a particular loading mechanism, active symplasmic loading, also called the polymer trap mechanism, where sucrose is transformed into heavier sugars, such as raffinose and stachyose, in the intermediary-type companion cells bordering the sieve elements in the minor veins of the phloem. Keeping the heavier sugars from diffusing back requires that the plasmodesmata connecting the bundle sheath with the intermediary cell act as extremely precise filters, which are able to distinguish between molecules that differ by less than 20% in size. In our modeling, we take into account the coupled water and sugar movement across the relevant interfaces, without explicitly considering the chemical reactions transforming the sucrose into the heavier sugars. Based on the available data for plasmodesmata geometry, sugar concentrations, and flux rates, we conclude that this mechanism can in principle function, but that it requires pores of molecular sizes. Comparing with the somewhat uncertain experimental values for sugar export rates, we expect the pores to be only 5%-10% larger than the hydraulic radius of the sucrose molecules. We find that the water flow through the plasmodesmata, which has not been quantified before, contributes only 10%-20% to the sucrose flux into the intermediary cells, while the main part is transported by diffusion. On the other hand, the subsequent sugar translocation into the sieve elements would very likely be carried predominantly by bulk water flow through the plasmodesmata. Thus, in contrast to apoplasmic loaders, all the necessary water for phloem translocation would be supplied in this way with no need for additional water uptake across the plasma membranes of the phloem.

Analyses of the 1981-82 Illinois Public Library Statistics.

ERIC Educational Resources Information Center

Wallace, Danny P.

Using data provided by the annual reports of Illinois public libraries and by the Illinois state library, this publication is a companion to the November 1982 issue of "Illinois Libraries," which enumerated the 16 data elements upon which the analyses are based. Three additional types of information are provided for each of six…

Apparel and Textiles Production, Management, and Services. Curriculum Guide.

ERIC Educational Resources Information Center

Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

Developed with input from personnel in the industries, this curriculum guide complements a companion reference book about various areas of the textiles and apparel industries. Each of the 22 chapters of the guide begins with 1 or more essential elements and objectives, and each chapter consists of teaching strategies for classroom use. Teaching…

The Voroshilov Lectures. Materials from the Soviet General Staff Academy. Volume 1. Issues of Soviet Military Strategy,

DTIC Science & Technology

1989-06-01

army defensive operation, this was the companion course to the material presented in the third semester on front offensive operations. In addition, a...center and supporting elements. Glossary 359 KOSMICHESKAIA SISTEMA Space system: A grouping of space and ground-based forces and means assigned to

Examining the nexus between domestic violence and animal abuse in a national sample of service providers.

PubMed

Krienert, Jessie L; Walsh, Jeffrey A; Matthews, Kevin; McConkey, Kelly

2012-01-01

Companion animals play a complex role in families impacted by violence. An outlet of emotional support for victims, the family pet often becomes a target for physical abuse. Results from a comprehensive e-survey of domestic violence shelters nationwide (N = 767) highlight both improvements and existing gaps in service provision for domestic violence victims and their pets. Quantitative and qualitative data noted frequently encountered obstacles to successful shelter seeking by abuse victims with companion animals including a lack of availability, funding, space, and reliable programming. Although results indicate an overall improvement in organizational awareness, fewer than half of surveyed shelters include intake questions about animals. Continued awareness and an expansion of services is needed to create viable safety planning strategies and reliable alternatives for women with companion animals in order to improve the likelihood that abuse victims will seek escape and refuge for themselves, their children, and their pets.

KELT-19Ab: A P ∼ 4.6-day Hot Jupiter Transiting a Likely Am Star with a Distant Stellar Companion

NASA Astrophysics Data System (ADS)

Siverd, Robert J.; Collins, Karen A.; Zhou, George; Quinn, Samuel N.; Gaudi, B. Scott; Stassun, Keivan G.; Johnson, Marshall C.; Bieryla, Allyson; Latham, David W.; Ciardi, David R.; Rodriguez, Joseph E.; Penev, Kaloyan; Pinsonneault, Marc; Pepper, Joshua; Eastman, Jason D.; Relles, Howard; Kielkopf, John F.; Gregorio, Joao; Oberst, Thomas E.; Aldi, Giulio Francesco; Esquerdo, Gilbert A.; Calkins, Michael L.; Berlind, Perry; Dressing, Courtney D.; Patel, Rahul; Stevens, Daniel J.; Beatty, Thomas G.; Lund, Michael B.; Labadie-Bartz, Jonathan; Kuhn, Rudolf B.; Colón, Knicole D.; James, David; Yao, Xinyu; Johnson, John A.; Wright, Jason T.; McCrady, Nate; Wittenmyer, Robert A.; Johnson, Samson A.; Sliski, David H.; Jensen, Eric L. N.; Cohen, David H.; McLeod, Kim K.; Penny, Matthew T.; Joner, Michael D.; Stephens, Denise C.; Villanueva, Steven, Jr.; Zambelli, Roberto; Stockdale, Christopher; Evans, Phil; Tan, Thiam-Guan; Curtis, Ivan A.; Reed, Phillip A.; Trueblood, Mark; Trueblood, Patricia

2018-01-01

We present the discovery of the giant planet KELT-19Ab, which transits the moderately bright (V∼ 9.9) A8V star TYC 764-1494-1 with an orbital period of 4.61 days. We confirm the planetary nature of the companion via a combination of radial velocities, which limit the mass to ≲ 4.1 {M}{{J}} (3σ ), and a clear Doppler tomography signal, which indicates a retrograde projected spin–orbit misalignment of λ =-{179.7}-3.8+3.7 degrees. Global modeling indicates that the {T}{eff}=7500+/- 110 K host star has {M}\\star ={1.62}-0.20+0.25 {M}ȯ and {R}\\star =1.83+/- 0.10 {R}ȯ . The planet has a radius of {R}P=1.91+/- 0.11 {R}{{J}} and receives a stellar insolation flux of ∼ 3.2× {10}9 {erg} {{{s}}}-1 {{cm}}-2, leading to an inferred equilibrium temperature of {T}{eq}∼ 1935 K assuming zero albedo and complete heat redistribution. With a v\\sin {I}* =84.8+/- 2.0 {km} {{{s}}}-1, the host is relatively slowly rotating compared to other stars with similar effective temperatures, and it appears to be enhanced in metallic elements but deficient in calcium, suggesting that it is likely an Am star. KELT-19A would be the first detection of an Am host of a transiting planet of which we are aware. Adaptive optics observations of the system reveal the existence of a companion with late-G9V/early-K1V spectral type at a projected separation of ≈ 160 {au}. Radial velocity measurements indicate that this companion is bound. Most Am stars are known to have stellar companions, which are often invoked to explain the relatively slow rotation of the primary. In this case, the stellar companion is unlikely to have caused the tidal braking of the primary. However, it may have emplaced the transiting planetary companion via the Kozai–Lidov mechanism.

The barium-to-iron enrichment versus age relation of ancient disc stars

NASA Astrophysics Data System (ADS)

Fuhrmann, K.; Chini, R.; Kaderhandt, L.; Chen, Z.; Lachaume, R.

2017-11-01

We report an intrinsically precise relation of the barium-to-iron enrichment as a function of age for a local, volume-complete (N = 30) sample of ancient Population II (τ ≥ 12 Gyr) and intermediate-disc stars (τ ≃ 10 Gyr), which suggests a common, r-process-dominated nucleosynthesis site for both elements in the early stages of the Milky Way. Deviants from this empirical relation are to a large extent identified as formerly known or new blue straggler stars. We report in particular the striking case of the Population II star HD 159062, whose barium overabundance is difficult to explain without wind accretion of s-process material from a former asymptotic giant branch (AGB) primary that very likely survived as a white dwarf companion. The weak but significant barium enhancement that we measure for HR 3578 and 104 Tau also suggests that both may be accompanied by faint degenerate companions. If confirmed through precision astrometry or direct imaging observations, this would mean a very efficient method to uncover ancient stellar remnant companions around solar-type stars.

Mutually Augmented Cognition

NASA Astrophysics Data System (ADS)

Friesdorf, Florian; Pangercic, Dejan; Bubb, Heiner; Beetz, Michael

In mac, an ergonomic dialog-system and algorithms will be developed that enable human experts and companions to be integrated into knowledge gathering and decision making processes of highly complex cognitive systems (e.g. Assistive Household as manifested further in the paper). In this event we propose to join algorithms and methodologies coming from Ergonomics and Artificial Intelligence that: a) make cognitive systems more congenial for non-expert humans, b) facilitate their comprehension by utilizing a high-level expandable control code for human experts and c) augment representation of such cognitive system into “deep representation” obtained through an interaction with human companions.

Quantitative spectral analysis of the sdB star HD 188112: A helium-core white dwarf progenitor

NASA Astrophysics Data System (ADS)

Latour, M.; Heber, U.; Irrgang, A.; Schaffenroth, V.; Geier, S.; Hillebrandt, W.; Röpke, F. K.; Taubenberger, S.; Kromer, M.; Fink, M.

2016-01-01

Context. HD 188112 is a bright (V = 10.2 mag) hot subdwarf B (sdB) star with a mass too low to ignite core helium burning and is therefore considered a pre-extremely low-mass (ELM) white dwarf (WD). ELM WDs (M ≲ 0.3 M⊙) are He-core objects produced by the evolution of compact binary systems. Aims: We present in this paper a detailed abundance analysis of HD 188112 based on high-resolution Hubble Space Telescope (HST) near- and far-ultraviolet spectroscopy. We also constrain the mass of the star's companion. Methods: We use hybrid non-LTE model atmospheres to fit the observed spectral lines, and to derive the abundances of more than a dozen elements and the rotational broadening of metallic lines. Results: We confirm the previous binary system parameters by combining radial velocities measured in our UV spectra with the previously published values. The system has a period of 0.60658584 days and a WD companion with M ≥ 0.70 M⊙. By assuming a tidally locked rotation combined with the projected rotational velocity (v sin I = 7.9 ± 0.3 km s-1), we constrain the companion mass to be between 0.9 and 1.3 M⊙. We further discuss the future evolution of the system as a potential progenitor of an underluminous type Ia supernova. We measure abundances for Mg, Al, Si, P, S, Ca, Ti, Cr, Mn, Fe, Ni, and Zn, and for the trans-iron elements Ga, Sn, and Pb. In addition, we derive upper limits for the C, N, O elements and find HD 188112 to be strongly depleted in carbon. We find evidence of non-LTE effects on the line strength of some ionic species such as Si II and Ni II. The metallic abundances indicate that the star is metal-poor, with an abundance pattern most likely produced by diffusion effects.

The role of metals in carcinogenesis: biochemistry and metabolism.

PubMed Central

Jennette, K W

1981-01-01

The oxyanions of vanadium, chromium, molybdenum, arsenic, and selenium are stable forms of these elements in high oxidation states which cross cell membranes using the normal phosphate and/or sulfate transport systems of the cell. Once inside the cell, these oxyanions may sulfuryl transfer reactions. Often the oxyanions serve as alternate enzyme substrates but form ester products which are hydrolytically unstable compared with the sulfate and phosphate esters and, therefore, decompose readily in aqueous solution. Arsenite and selenite are capable of reacting with sulfhydryl groups in proteins. Some cells are able to metabolize redox active oxyanions to forms of the elements in other stable oxidation states. Specific enzymes may be involved in the metabolic processes. The metabolites of these elements may form complexes with small molecules, proteins and nucleic acids which inhibit their ability to function properly. The divalent ions of beryllium, manganese, cobalt, nickel, cadmium, mercury, and lead are stable forms of these elements which may mimic essential divalent ions such as magnesium, calcium, iron, copper, or zinc. These ions may complex small molecules, enzymes, and nucleic acids in such a way that the normal activity of these species is altered. Free radicals may be produced in the presence of these metal ions which damage critical cellular molecules. PMID:7023933

VLTI-Pionier Imaging of the Carbon AGB Star R Sculptoris and the Supergiant V766 Centauri

NASA Astrophysics Data System (ADS)

Wittkowski, Markus

2018-04-01

I will present reconstructed images of the carbon-rich AGB star R Scl and of the supergiant V766 Cen, both recently obtained from VLTI-PIONIER data. The images are compared to state-of-the art atmosphere and wind models. The images of R Scl exhibit a complex structure within the stellar disk. This structure is most likely caused by giant convection cells, resulting in large-scale shock fronts, and their effects on clumpy molecule and dust formation seen against the photosphere. Images of V 766 Cen were obtained at three epochs. The first epoch shows a complex elongated structure within the photospheric disk, consistent with a red supergiant harboring giant photospheric convection cells. The second and third epochs show a qualitatively and quantitatively different structure with significantly increased contrast, which is not compatible with current models of convection. Instead we interpret the 2016 and 2017 epochs as showing a previously suggested close eclipsing companion in front of the primary, which was located behind the primary at the 2014 epoch. Finally, I will show preliminary reconstructed images of a small sample of further red supergiants.

Quantitative analysis of biomedical samples using synchrotron radiation microbeams

NASA Astrophysics Data System (ADS)

Ektessabi, Ali; Shikine, Shunsuke; Yoshida, Sohei

2001-07-01

X-ray fluorescence (XRF) using a synchrotron radiation (SR) microbeam was applied to investigate distributions and concentrations of elements in single neurons of patients with neurodegenerative diseases. In this paper we introduce a computer code that has been developed to quantify the trace elements and matrix elements at the single cell level. This computer code has been used in studies of several important neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) and parkinsonism-dementia complex (PDC), as well as in basic biological experiments to determine the elemental changes in cells due to incorporation of foreign metal elements. The substantial nigra (SN) tissue obtained from the autopsy specimens of patients with Guamanian parkinsonism-dementia complex (PDC) and control cases were examined. Quantitative XRF analysis showed that neuromelanin granules of Parkinsonian SN contained higher levels of Fe than those of the control. The concentrations were in the ranges of 2300-3100 ppm and 2000-2400 ppm respectively. On the contrary, Zn and Ni in neuromelanin granules of SN tissue from the PDC case were lower than those of the control. Especially Zn was less than 40 ppm in SN tissue from the PDC case while it was 560-810 ppm in the control. These changes are considered to be closely related to the neuro-degeneration and cell death.

Structural Elements Recognized by Abacavir-Induced T Cells.

PubMed

Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J; Eriksson, Klara K; Strhyn, Anette; Bracey, Austin W; Buus, Soren; Ostrov, David A

2017-07-07

Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976-984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230-238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues.

Cell Phones for Education

ERIC Educational Resources Information Center

Roberson, James H.; Hagevik, Rita A.

2008-01-01

Cell phones are fast becoming an integral part of students' everyday lives. They are regarded as important companions and tools for personal expression. School-age children are integrating the cell phone as such, and thus placing a high value on them. Educators endeavor to instill in students a high value for education, but often meet with…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dahabieh, Matthew S., E-mail: dahabieh@interchange.ubc.ca; Ooms, Marcel, E-mail: marcel.ooms@mssm.edu; Malcolm, Tom, E-mail: tmalc1@yahoo.com

Transcription from the HIV-1 long terminal repeat (LTR) is mediated by numerous host transcription factors. In this study we characterized an E-box motif (RBE1) within the core promoter that was previously implicated in both transcriptional activation and repression. We show that RBE1 is a binding site for the RBF-2 transcription factor complex (USF1, USF2, and TFII-I), previously shown to bind an upstream viral element, RBE3. The RBE1 and RBE3 elements formed complexes of identical mobility and protein constituents in gel shift assays, both with Jurkat T-cell nuclear extracts and recombinant USF/TFII-I. Furthermore, both elements are regulators of HIV-1 expression; mutationsmore » in LTR-luciferase reporters and in HIV-1 molecular clones resulted in decreased transcription, virion production, and proviral expression in infected cells. Collectively, our data indicate that RBE1 is a bona fide RBF-2 binding site and that the RBE1 and RBE3 elements are necessary for mediating proper transcription from the HIV-1 LTR.« less

Rapid Genetic Analysis of Epithelial-Mesenchymal Signaling During Hair Regeneration

PubMed Central

Zhen, Hanson H.; Oro, Anthony E.

2013-01-01

Hair follicle morphogenesis, a complex process requiring interaction between epithelia-derived keratinocytes and the underlying mesenchyme, is an attractive model system to study organ development and tissue-specific signaling. Although hair follicle development is genetically tractable, fast and reproducible analysis of factors essential for this process remains a challenge. Here we describe a procedure to generate targeted overexpression or shRNA-mediated knockdown of factors using lentivirus in a tissue-specific manner. Using a modified version of a hair regeneration model 5, 6, 11, we can achieve robust gain- or loss-of-function analysis in primary mouse keratinocytes or dermal cells to facilitate study of epithelial-mesenchymal signaling pathways that lead to hair follicle morphogenesis. We describe how to isolate fresh primary mouse keratinocytes and dermal cells, which contain dermal papilla cells and their precursors, deliver lentivirus containing either shRNA or cDNA to one of the cell populations, and combine the cells to generate fully formed hair follicles on the backs of nude mice. This approach allows analysis of tissue-specific factors required to generate hair follicles within three weeks and provides a fast and convenient companion to existing genetic models. PMID:23486463

Technology Status: Fuel Cells and Electrolysis Cells

NASA Technical Reports Server (NTRS)

Mcbryar, H.

1978-01-01

The status of the baselined shuttle fuel cell as well as the acid membrane fuel cell and space-oriented water electrolysis technologies are presented. The more recent advances in the alkaline fuel cell technology area are the subject of a companion paper. A preliminary plan for the focusing of these technologies towards regenerative energy storage applications in the multi-hundred kilowatt range is also discussed.

Planet formation: is it good or bad to have a stellar companion?

NASA Astrophysics Data System (ADS)

Marzari, F.; Thebault, P.; Scholl, H.

2010-04-01

Planet formation in binary star systems is a complex issue due to the gravitational perturbations of the companion star. One of the crucial steps of the core-accretion model is planetesimal accretion into large protoplanets which finally coalesce into planets. In a planetesimal swarm surrounding the primary star, the average mutual impact velocity determines if larger bodies form or if the population is grinded down to dust, halting the planet formation process. This velocity is strongly influenced by the companion gravitational pull and by gas drag. The combined effect of these two forces may act in favour of or against planet formation, setting a lower or equal probability of the existence of extrasolar planets around single or binary stars. Planetesimal accretion in binaries has been studied so far with two different approaches. N-body codes based on the assumption that the disk is axisymmetric are very cost-effective since they allow the study of the mutual relative velocity with limited CPU usage. A large amount of planetesimal trajectories can be computed making it possible to outline the regions around the star where planet formation is possible. The main limitation of the N-body codes is the axisymmetric assumption. The companion perturbations affect not only the planetesimal orbits, but also the gaseous disk, by forcing spiral density waves. In addition, the overall shape of the disk changes from circular to elliptic. Hybrid codes have been recently developed which solve the equations for the disk with a hydrodynamical grid code and use the computed gas density and velocity vector to calculate an accurate value of the gas drag force on the planetesimals. These codes are more complex and may compute the trajectories of only a limited number of planetesimals.

California Community College Family and Consumer Sciences in the 21st Century.

ERIC Educational Resources Information Center

California Community Colleges, Sacramento. Office of the Chancellor.

Prepared as a companion to a 1996 California Community College plan for family and consumer sciences (FCS), this resource packet provides materials to help faculty, administrators, counselors, and other educators understand the elements of the plan, sharpen their focus on the dynamics of FCS programs, and increase support for programs at their…

Key Elements of Observing Practice: A Data Wise DVD and Facilitator's Guide

ERIC Educational Resources Information Center

Boudett, Kathryn Parker; City, Elizabeth A.; Russell, Marcia K.

2010-01-01

Based on the bestselling book "Data Wise: A Step-by-Step Guide to Using Assessment Results to Improve Teaching and Learning", and its companion volume, "Data Wise in Action", this DVD and Facilitator's Guide offer insight into one of the most challenging steps in capturing data about school performance: observing and analyzing instructional…

Examining an underappreciated control on lignin decomposition in soils? Effects of reactive manganese species on intact plant cell walls

NASA Astrophysics Data System (ADS)

Keiluweit, M.; Bougoure, J.; Pett-Ridge, J.; Kleber, M.; Nico, P. S.

2011-12-01

Lignin comprises a dominant proportion of carbon fluxes into the soil (representing up to 50% of plant litter and roots). Two lines of evidence suggest that manganese (Mn) acts as a strong controlling factor on the residence time of lignin in soil ecosystems. First, Mn content is highly correlated with litter decomposition in temperate and boreal forest soil ecosystems and, second, microbial agents of lignin degradation have been reported to rely on reactive Mn(III)-complexes to specifically oxidize lignin. However, few attempts have been made to isolate the mechanisms responsible for the apparent Mn-dependence of lignin decomposition in soils. Here we tested the hypothesis that Mn(III)-oxalate complexes may act as a perforating 'pretreatment' for structurally intact plant cell walls. We propose that these diffusible oxidizers are small enough to penetrate and react with non-porous ligno-cellulose in cell walls. This process was investigated by reacting single Zinnia elegans tracheary elements with Mn(III)-oxalate complexes in a continuous flow-through microreactor. The uniformity of cultured tracheary elements allowed us to examine Mn(III)-induced changes in cell wall chemistry and ultrastructure on the micro-scale using fluorescence and electron microscopy as well as synchrotron-based infrared and X-ray spectromicroscopy. Our results show that Mn(III)-complexes substantially oxidize specific lignin components of the cell wall, solubilize decomposition products, severely undermine the cell wall integrity, and cause cell lysis. We conclude that Mn(III)-complexes induce oxidative damage in plant cell walls that renders ligno-cellulose substrates more accessible for microbial lignin- and cellulose-decomposing enzymes. Implications of our results for the rate limiting impact of soil Mn speciation and availability on litter decomposition in forest soils will be discussed.

Combustion Dynamics and Stability Modeling of a Liquid Oxygen/RP-2 Oxygen-Rich Staged Combustion Preburner and Thrust Chamber Assembly with Gas-Centered Swirl Coaxial Injector Elements

NASA Technical Reports Server (NTRS)

Casiano, M. J.; Kenny, R. J.; Protz, C. S.; Garcia, C. P.; Simpson, S. P.; Elmore, J. L.; Fischbach, S. R.; Giacomoni, C. B.; Hulka, J. R.

2016-01-01

The Combustion Stability Tool Development (CSTD) project, funded by the Air Force Space and Missile Systems Center, began in March 2015 supporting a renewed interest in the development of a liquid oxygen/hydrocarbon, oxygen-rich combustion engine. The project encompasses the design, assembly, and hot-fire testing of the NASA Marshall Space Flight Center 40-klbf Integrated Test Rig (MITR). The test rig models a staged-combustion configuration by combining an oxygen-rich preburner (ORPB), to generate hot gas, with a thrust chamber assembly (TCA) using gas-centered swirl coaxial injector elements. There are five separately designed interchangeable injectors in the TCA that each contain 19- or 27- injector elements. A companion paper in this JANNAF conference describes the design characteristics, rationale, and fabrication issues for all the injectors. The data acquired from a heavily instrumented rig encompasses several injectors, several operating points, and stability bomb tests. Another companion paper in this JANNAF conference describes this test program in detail. In this paper, dynamic data from the hot-fire testing is characterized and used to identify the responses in the ORPB and TCA. A brief review of damping metrics are discussed and applied as a measure of stability margin for damped acoustic modes. Chug and longitudinal combustion stability models and predictions are described which includes new dynamic models for compressible flow through an orifice and a modification to incorporate a third feed line for inclusion of the fuel-film coolant. Flow-acoustics finite element modeling is used to investigate the anticipated TCA acoustics, the effects of injector element length on stability margin, and the potential use of an ORPB orifice trip ring for improving longitudinal stability margin.

Synthesis, characterization and biological activities of copper(II) complex of 2-Benzimidazolyl-urea and the nitrate salt of 2-Benzimidazolyl-urea

NASA Astrophysics Data System (ADS)

Poyraz, Mehmet; Sari, Musa; Banti, Christina N.; Hadjikakou, Sotiris K.

2017-10-01

The synthesis of the complex {[Cu(BZIMU)2](NO3)2} (1) (BZIMU = 2-Benzimidazolyl-urea) is reported here. The complex 1 was characterized by elemental analysis, FT-IR, magnetic susceptibility and molar conductance measurements. The crystal structures of 1 and of the nitrate salt of [(BZIMUH+)(NO3)-] (2) were determined by X-ray diffraction analysis. The copper complex 1 and [(BZIMUH+)(NO3)-] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cervix adenocarcinoma (HeLa) and human breast adenocarcinoma (MCF-7) cell line and normal human fetal lung fibroblast cells (MRC-5) with SRB assay.

Secondary phloem diversity and evolution in Bignonieae (Bignoniaceae)

PubMed Central

Pace, Marcelo R.; Alcantara, Suzana; Lohmann, Lúcia G.; Angyalossy, Veronica

2015-01-01

Background and Aims Phloem evolution has been explored in the literature across very broad scales, either for vascular plants as a whole or for major plant groups, such as the monocotyledons or the former dicotyledons. However, it has never been examined in a way that would elucidate evolutionary shifts leading to the diversification of phloem in single lineages. Therefore, the present study explores in detail the patterns of phloem evolution in the tribe Bignonieae (Bignoniaceae). This group represents a particularly good model for phloem studies since it is known to have a very conspicuous and diverse phloem. Methods A total of 19 phloem characters were coded in 56 species from all 21 genera currently recognized in the tribe Bignonieae, accounting for phloem wedge growth and for all the anatomical cell diversity encountered in the phloem. Phloem evolution was explored by reconstructing ancestral character states using maximum-likelihood assumptions with a time-calibrated molecular phylogeny for the group. Directionality and the effect of phylogenetic transformations in the current variation of quantitative traits and evolutionary correlations of selected discrete phloem traits were also tested under a maximum-likelihood approach. Key Results Individual phloem features are quite diverse in the tribe, but generally conserved within smaller clades. Contrasting phloem patterns were found when comparing major groups, with certain lineages having the phloem marked by a background of phloem fibres where all other cells are embedded, tangentially arranged sieve tubes and sieve-tubecentric parenchyma. In contrast, other lineages exhibited a scarcely fibrous phloem, regularly stratified phloem, sieve tube elements in radial or diffuse arrangement, and diffuse parenchyma. We found signals of directional evolution in fibre abundance and number of sieve areas, which increased in the ‘Fridericia and allies extended clade’ and decreased in the ‘Multiples of four extended clade’, resulting in no signal of directionality when the whole Bignonieae was considered. In contrast, no indication of directional evolution was found for the axial parenchyma, either in single clades within Bignonieae or in the entire tribe. Positive correlation was found between sieve element length and both sieve plate type and the presence of a storied structure. Correlated evolution was also found between fibre abundance and several traits, such as sieve tube arrangement, sieve plate type, parenchyma arrangement, ray lignification and number of companion cells. Conclusions The secondary phloem of Bignonieae is extremely diverse, with sister lineages exhibiting distinct phloem anatomies derived from contrasting patterns of evolution in fibre abundance. Fibre abundance in the tribe has diversified in correlation with sieve tube arrangement, sieve tube morphology, number of companion cells and parenchyma type. The results challenge long-standing hypotheses regarding general trends in cell abundance and morphological cell evolution within the phloem, and demonstrate the need to expand studies in phloem anatomy both at a narrow taxonomic scale and at a broad one, such as to families and orders. PMID:26311709

Androgen receptor stimulates bone sialoprotein (BSP) gene transcription via cAMP response element and activator protein 1/glucocorticoid response elements.

PubMed

Takai, Hideki; Nakayama, Youhei; Kim, Dong-Soon; Arai, Masato; Araki, Shouta; Mezawa, Masaru; Nakajima, Yu; Kato, Naoko; Masunaga, Hiroshi; Ogata, Yorimasa

2007-09-01

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. Androgens are steroid hormones that are essential for skeletal development. The androgen receptor (AR) is a transcription factor and a member of the steroid receptor superfamily that plays an important role in male sexual differentiation and prostate cell proliferation. To determine the molecular mechanism involved in the stimulation of bone formation, we have analyzed the effects of androgens and AR effects on BSP gene transcription. AR protein levels were increased after AR overexpression in ROS17/2.8 cells. BSP mRNA levels were increased by AR overexpression. However, the endogenous and overexpressed BSP mRNA levels were not changed by DHT (10(-8) M, 24 h). Whereas luciferase (LUC) activities in all constructs, including a short construct (nts -116 to +60), were increased by AR overexpression, the basal and LUC activities enhanced by AR overexpression were not induced by DHT (10(-8)M, 24 h). The effect of AR overexpression was abrogated by 2 bp mutations in either the cAMP response element (CRE) or activator protein 1 (AP1)/glucocorticoid response element (GRE). Gel shift analyses showed that AR overexpression increased binding to the CRE and AP1/GRE elements. Notably, the CRE-protein complexes were supershifted by phospho-CREB antibody, and CREB, c-Fos, c-Jun, and AR antibodies disrupted the complexes formation. The AP1/GRE-protein complexes were supershifted by c-Fos antibody and c-Jun, and AR antibodies disrupted the complexes formation. These studies demonstrate that AR stimulates BSP gene transcription by targeting the CRE and AP1/GRE elements in the promoter of the rat BSP gene.

Ecology as a Unifying Theme for Home Economics/Human Ecology.

ERIC Educational Resources Information Center

Vaines, Eleanore

1994-01-01

Discusses the complex character of everyday life as the deep ecology of Home Economics/Human Ecology. Explores the meanings of ecology and the ways in which diversity and harmony are interrelated companions of dynamic living systems. (JOW)

HE 0017+0055: A probable pulsating CEMP-rs star and long-period binary

NASA Astrophysics Data System (ADS)

Jorissen, A.; Hansen, T.; Van Eck, S.; Andersen, J.; Nordström, B.; Siess, L.; Torres, G.; Masseron, T.; Van Winckel, H.

2016-02-01

Context. A large fraction of the carbon-enhanced, extremely metal-poor halo giants ([Fe/H] < -2.5) are also strongly enriched in neutron-capture elements from the s process (CEMP-s stars). The conventional explanation for the properties of these stars is mass transfer from a nearby binary companion on the asymptotic giant branch (AGB). This scenario leads to a number of testable predictions in terms of the properties of the putative binary system and the resulting abundance pattern. Among the CEMP stars, some stars further exhibit overabundances in r-process elements on top of the s-process enrichment, and are tagged CEMP-rs stars. Although the nucleosynthesis process responsible for this kind of mixed abundance pattern is still under debate, CEMP-rs stars seem to belong to binary systems as do CEMP-s stars. Aims: Our aim is to present and analyse in detail our comprehensive data set of systematic radial-velocity measurements and high-resolution spectroscopy of the CEMP star HE 0017+0055. Methods: Our precise radial-velocity monitoring of HE 0017+0055 over 2940 days (8 yr) with the Nordic Optical Telescope and Mercator telescopes exhibits variability, with a period of 384 d and amplitude of 540 ± 27 m s-1 superimposed on a nearly linear long-term decline of ~1 m s-1 day-1. We used high-resolution HERMES/Mercator and Keck/HIRES spectra to derive elemental abundances with 1D LTE MARCS models. A metallicity of [Fe/H] ~ -2.4 is found, along with s-process overabundances of the order of 2 dex (with the exception of [Y/Fe] ~ + 0.5), and most notably overabundances of r-process elements like Sm, Eu, Dy, and Er in the range 0.9-2.0 dex. With [Ba/Fe] > 1.9 dex and [Eu/Fe] = 2.3 dex, HE 0017+0055 is a CEMP-rs star. We used the derived atmospheric parameters and abundances to infer HE 0017+0055 evolutionary status from a comparison with evolutionary tracks. Results: HE 0017+0055 appears to be a giant star below the tip of the red giant branch. The s-process pollution must therefore originate from mass transfer from a companion formerly on the AGB, which is now a carbon-oxygen white dwarf (WD). If the 384 d velocity variations are attributed to the WD companion, its orbit must be seen almost face-on, with I ~ 2.3°, because the mass function is very small: f(M1,M2) = (6.1 ± 1.1) × 10-6M⊙. Alternatively, the WD orbital motion could be responsible for the long-term velocity variations, with a period of several decades. The 384 d variations should then be attributed either to a low-mass inner companion (perhaps a brown dwarf, depending on the orbital inclination), or to stellar pulsations. The latter possibility is made likely by the fact that similar low-amplitude velocity variations, with periods close to 1 yr, have been reported for other CEMP stars in a companion paper. A definite conclusion about the origin of the 384 d velocity variations should however await the detection of synchronous low-amplitude photometric variations. Based on observations performed with the Mercator telescope and the Nordic Optical Telescope (NOT), operated by the Nordic Optical Telescope Scientific Association at the Roque de los Muchachos Observatory, La Palma, Spain, of the Instituto de Astrofïsica de Canarias.

A new insight into the three-dimensional architecture of the Golgi complex: Characterization of unusual structures in epididymal principal cells

PubMed Central

Martínez-Martínez, Narcisa; Martínez-Alonso, Emma; Tomás, Mónica; Neumüller, Josef; Pavelka, Margit

2017-01-01

Principal epididymal cells have one of the largest and more developed Golgi complex of mammalian cells. In the present study, we have used this cell as model for the study of the three-dimensional architecture of the Golgi complex of highly secretory and endocytic cells. Electron tomography demonstrated the presence in this cell type of some unknown or very unusual Golgi structures such as branched cisternae, pocket-like cisternal invaginations or tubular connections. In addition, we have used this methodology and immunoelectron microscopy to analyze the close relationship between this organelle and both the endoplasmic reticulum and microtubules, and to describe in detail how these elements interact with compact and non-compact regions of the ribbon. PMID:28957389

From Metaphors to Models: Broadening the Lens of the Hunter Warrior Experiment with a Complex Adaptive System Tool

DTIC Science & Technology

1999-01-01

chemistry tells us why it is inevitable, pervasive, and won’t go away. Fortunately, there is the companion new science of complexity, rooted in...article. 30llachinski, Land Warfare and Complexity, Part II, 43. 32 Ilachinski, 43. Etymologically , metaphor (the Greek metafora, "carry over") means...anthropology, chemistry , economics, military and political science among others. Santa Fe Institute, http://www.santafe.edu/sfl/research. 53SAIC

High-resolution genome-wide scan of genes, gene-networks and cellular systems impacting the yeast ionome

USDA-ARS?s Scientific Manuscript database

To balance the demand for uptake of essential elements with their potential toxicity living cells have complex regulatory mechanisms. Here, we describe a genome-wide screen to identify genes that impact the elemental composition (‘ionome’) of yeast Saccharomyces cerevisiae. Using inductively coupled...

How Does CIGS Performance Depend on Temperature at the Microscale?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stuckelberger, Michael E.; Nietzold, Tara; West, Bradley M.

Unveiling the correlation among electrical performance, elemental distribution, and defects at the microscale is crucial for the understanding and improvement of the overall solar cell performance. While this is true in general for solar cells with polycrystalline absorber layers, it is particularly critical for defect engineering of the complex quaternary CuIn xGa 1-xSe 2 (CIGS) material system. Studying these relationships under standard ambient conditions can provide important insights but does not provide input on the behavior of the cell under real operating conditions. In this contribution, we take a close look at the complex temperature dependence of defects and voltagemore » in CIGS at the microscale. We have developed correlative X-raymicroscopymethods and adapted them for temperature-dependent measurements of the locally generated voltage and elemental compositions at the microscale. We have applied these techniques to industrial CIGS solar cells covering temperatures from room temperature up to 100 degrees C. Finally, we find underperforming areas spanning multiple grains that do not correlate with the elemental distribution of major absorber constituents. However, we demonstrate that low-performing areas perform better at higher temperatures relative to the high-performing areas.« less

How Does CIGS Performance Depend on Temperature at the Microscale?

DOE PAGES

Stuckelberger, Michael E.; Nietzold, Tara; West, Bradley M.; ...

2017-11-03

Unveiling the correlation among electrical performance, elemental distribution, and defects at the microscale is crucial for the understanding and improvement of the overall solar cell performance. While this is true in general for solar cells with polycrystalline absorber layers, it is particularly critical for defect engineering of the complex quaternary CuIn xGa 1-xSe 2 (CIGS) material system. Studying these relationships under standard ambient conditions can provide important insights but does not provide input on the behavior of the cell under real operating conditions. In this contribution, we take a close look at the complex temperature dependence of defects and voltagemore » in CIGS at the microscale. We have developed correlative X-raymicroscopymethods and adapted them for temperature-dependent measurements of the locally generated voltage and elemental compositions at the microscale. We have applied these techniques to industrial CIGS solar cells covering temperatures from room temperature up to 100 degrees C. Finally, we find underperforming areas spanning multiple grains that do not correlate with the elemental distribution of major absorber constituents. However, we demonstrate that low-performing areas perform better at higher temperatures relative to the high-performing areas.« less

Structural Elements Recognized by Abacavir-Induced T Cells

PubMed Central

Yerly, Daniel; Pompeu, Yuri Andreiw; Schutte, Ryan J.; Eriksson, Klara. K.; Strhyn, Anette; Bracey, Austin. W.; Buus, Soren; Ostrov, David A.

2017-01-01

Adverse drug reactions are one of the leading causes of morbidity and mortality in health care worldwide. Human leukocyte antigen (HLA) alleles have been strongly associated with drug hypersensitivities, and the causative drugs have been shown to stimulate specific T cells at the sites of autoimmune destruction. The structural elements recognized by drug-specific T cell receptors (TCRs) in vivo are poorly defined. Drug-stimulated T cells express TCRs specific for peptide/HLA complexes, but the characteristics of peptides (sequence, or endogenous or exogenous origin) presented in the context of small molecule drugs are not well studied. Using HLA-B*57:01 mediated hypersensitivity to abacavir as a model system, this study examines structural similarities of HLA presented peptides recognized by drug-specific TCRs. Using the crystal structure of HLA-B*57:01 complexed with abacavir and an immunogenic self peptide, VTTDIQVKV SPT5a 976–984, peptide side chains exhibiting flexibility and solvent exposure were identified as potential drug-specific T cell recognition motifs. Viral sequences with structural motifs similar to the immunogenic self peptide were identified. Abacavir-specific T cell clones were used to determine if virus peptides presented in the context of abacavir stimulate T cell responsiveness. An abacavir-specific T cell clone was stimulated by VTQQAQVRL, corresponding to HSV1/2 230–238, in the context of HLA-B*57:01. These data suggest the T cell polyclonal response to abacavir consists of multiple subsets, including T cells that recognize self peptide/HLA-B*57:01 complexes and crossreact with viral peptide/HLA-B*57:01 complexes due to similarity in TCR contact residues. PMID:28686208

Search for companions in visual binary systems using precise radial-velocity measurements

NASA Astrophysics Data System (ADS)

Katoh, Noriyuki; Itoh, Yoichi; Sato, Bun'ei

2018-05-01

The frequency of triple and quadruple systems is considered to be high in the early phase of star formation. Some multiple systems decay in the pre-main-sequence phase. The multiplicity of main-sequence stars provides clues about the evolution of binary systems. This work searched for companions of five components of visual binary systems using precise radial-velocity measurements. Their radial velocities were monitored from 2007 to 2012 using the HIgh Dispersion Echelle Spectrograph (HIDES) installed on the Okayama Astrophysical Observatory (OAO) 1.88 m reflector. In combination with previous work, this work searched for companions with an orbital period of less than 9 yr for the five bodies. We found periodic variations in the radial velocities for ADS 6190 A and BDS 10966A. The radial velocities of ADS 7311 A, 31 Dra A, and 31 Dra B show significant trends. ADS 6190 A is an SB1 binary with an orbital period of 366.2 d. The minimum mass of the secondary star is 0.5^{+0.7}_{-0.2} M_{⊙}. The radial velocity of ADS 7311 A was monitored for an observational span of 3200 d. We rejected a planetary-mass companion as the cause of a decreasing trend in the radial velocity of ADS 7311 A. This work confirmed that the periodic variation in the radial velocity of BDS 10966 A is 771.1 d. Bisector analysis did not reveal a correlation between the asymmetry of a spectral line and the radial velocity of BDS 10966 A. We rejected nonradial oscillation of the photosphere as the source of the radial velocity variation. The variation may be caused by the rotational modulation owing to surface inhomogeneity. The orbital elements of 31 Dra A derived in this paper are consistent with those in a previous paper. 31 Dra A system is an SB1 binary with a minimum mass ratio of 0.30 ± 0.08. 31 Dra B exhibits a periodic variation in radial velocity. The orbital elements derived in this work are consistent with those reported previously by others. The variation is caused by a circumstellar planet.

The Financial Costs, Behaviour and Psychology of Obesity: A One Health Analysis.

PubMed

Bomberg, E; Birch, L; Endenburg, N; German, A J; Neilson, J; Seligman, H; Takashima, G; Day, M J

2017-05-01

People who are overweight or have obesity are estimated to comprise 30% of the global population and up to 59% of companion dogs and cats are estimated to be above their optimal body weight. The prevalence of human and companion obesity is increasing. The direct and indirect costs of obesity and associated comorbidities are significant for human and veterinary healthcare. There are numerous similarities between obesity in people and companion animals, likely related to the shared environmental and lifestyle elements of this multifactorial disease. While the study of human obesity is relatively robust, research conducted in pets is generally limited to small studies, studies with cross-sectional designs or reports that have yet to be replicated. Greater understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. In particular, there are overlapping features of obesity in children and pets that are, in part, related to dependency on their 'parents' for care and feeding. When feeding is used in a coercive and controlling fashion, it may lead to undesirable feeding behaviour and increase the risk for obesity. A 'responsive parenting' intervention teaches parents to respond appropriately to hunger-satiety cues and to recognize and respond to others' distress. Such interventions may impact on childhood overweight and obesity and have the potential to be adapted for use with companion animals. Social behaviour towards people with obesity or owners of pets with obesity is often driven by beliefs about the cause of the obesity. Educating healthcare professionals and the public about the multifactorial nature of this complex disease process is a fundamental step in reducing the bias and stigma associated with obesity. Children living in low-income households have particularly high rates of obesity and as household income falls, rates of obesity also rise in pets and their owners. There are risk regulators (i.e. dynamic components of interconnected systems that influence obesity-related behaviours) and internal factors (i.e. biological determinants of obesity) that may influence the development of both childhood and pet obesity, and poverty may intersect with these variables to exacerbate obesity in low-income environments. This review discusses the costs, behaviours and psychology related to obesity in people and pets, and also proposes potential techniques that can be considered for prevention and treatment of this disease in pets. A 'One Health' approach to obesity suggests that an understanding of human obesity may elucidate some of the factors driving the more recent rise in pet obesity. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Role of Reactive Mn Complexes in a Litter Decomposition Model System

NASA Astrophysics Data System (ADS)

Nico, P. S.; Keiluweit, M.; Bougoure, J.; Kleber, M.; Summering, J. A.; Maynard, J. J.; Johnson, M.; Pett-Ridge, J.

2012-12-01

The search for controls on litter decomposition rates and pathways has yet to return definitive characteristics that are both statistically robust and can be understood as part of a mechanistic or numerical model. Herein we focus on Mn, an element present in all litter that is likely an active chemical agent of decomposition. Berg and co-workers (2010) found a strong correlation between Mn concentration in litter and the magnitude of litter degradation in boreal forests, suggesting that litter decomposition proceeds more efficiently in the presence of Mn. Although there is much circumstantial evidence for the potential role of Mn in lignin decomposition, few reports exist on mechanistic details of this process. For the current work, we are guided by the hypothesis that the dependence of decomposition on Mn is due to Mn (III)-oxalate complexes act as a 'pretreatment' for structurally intact ligno-carbohydrate complexes (LCC) in fresh plant cell walls (e.g. in litter, root and wood). Manganese (III)-ligand complexes such as Mn (III)-oxalate are known to be potent oxidizers of many different organic and inorganic compounds. In the litter system, the unique property of these complexes may be that they are much smaller than exo-enzymes and therefore more easily able to penetrate LCC complexes in plant cell walls. By acting as 'diffusible oxidizers' and reacting with the organic matrix of the cell wall, these compounds can increase the porosity of fresh litter thereby facilitating access of more specific lignin- and cellulose decomposing enzymes. This possibility was investigated by reacting cell walls of single Zinnia elegans tracheary elements with Mn (III)-oxalate complexes in a continuous flow reactor. The uniformity of these individual plant cells allowed us to examine Mn (III)-induced changes in cell wall chemistry and ultrastructure on the micro-scale using fluorescence and electron microscopy as well as IR and X-ray spectromicroscopy. This presentation will discuss the chemical changes induced by reaction of Mn (III)-complexes with the Zinnia cells, the impact of such reactions on cell integrity, and potential implications for soil C cycling.

Target Capabilities List: A Companion to the National Preparedness Guidelines

DTIC Science & Technology

2007-09-01

lowest possible geographic, organizational, and jurisdictional level using the principles in the National Incident Management System (NIMS). The...Response Plan. U.S. Department of Homeland Security. December 2004. 3. Biological Incident Annex. In the National Response Plan. U.S. Department of...elements of the continuum and improve interoperability, public safety and service agency practitioners should observe the following principles : Gain

An automated system for the study of ionospheric spatial structures

NASA Astrophysics Data System (ADS)

Belinskaya, I. V.; Boitman, O. N.; Vugmeister, B. O.; Vyborova, V. M.; Zakharov, V. N.; Laptev, V. A.; Mamchenko, M. S.; Potemkin, A. A.; Radionov, V. V.

The system is designed for the study of the vertical distribution of electron density and the parameters of medium-scale ionospheric irregularities over the sounding site as well as the reconstruction of the spatial distribution of electron density within the range of up to 300 km from the sounding location. The system comprises an active central station as well as passive companion stations. The central station is equipped with the digital ionosonde ``Basis'', the measuring-and-computing complex IVK-2, and the receiver-recorder PRK-3M. The companion stations are equipped with receivers-recorders PRK-3. The automated comlex software system includes 14 subsystems. Data transfer between them is effected using magnetic disk data sets. The system is operated in both ionogram mode and Doppler shift and angle-of-arrival mode. Using data obtained in these two modes, the reconstruction of the spatial distribution of electron density in the region is carried out. Reconstruction is checked for accuracy using data from companion stations.

In vitro selection of DNA elements highly responsive to the human T-cell lymphotropic virus type I transcriptional activator, Tax.

PubMed

Paca-Uccaralertkun, S; Zhao, L J; Adya, N; Cross, J V; Cullen, B R; Boros, I M; Giam, C Z

1994-01-01

The human T-cell lymphotropic virus type I (HTLV-I) transactivator, Tax, the ubiquitous transcriptional factor cyclic AMP (cAMP) response element-binding protein (CREB protein), and the 21-bp repeats in the HTLV-I transcriptional enhancer form a ternary nucleoprotein complex (L. J. Zhao and C. Z. Giam, Proc. Natl. Acad. Sci. USA 89:7070-7074, 1992). Using an antibody directed against the COOH-terminal region of Tax along with purified Tax and CREB proteins, we selected DNA elements bound specifically by the Tax-CREB complex in vitro. Two distinct but related groups of sequences containing the cAMP response element (CRE) flanked by long runs of G and C residues in the 5' and 3' regions, respectively, were preferentially recognized by Tax-CREB. In contrast, CREB alone binds only to CRE motifs (GNTGACG[T/C]) without neighboring G- or C-rich sequences. The Tax-CREB-selected sequences bear a striking resemblance to the 5' or 3' two-thirds of the HTLV-I 21-bp repeats and are highly inducible by Tax. Gel electrophoretic mobility shift assays, DNA transfection, and DNase I footprinting analyses indicated that the G- and C-rich sequences flanking the CRE motif are crucial for Tax-CREB-DNA ternary complex assembly and Tax transactivation but are not in direct contact with the Tax-CREB complex. These data show that Tax recruits CREB to form a multiprotein complex that specifically recognizes the viral 21-bp repeats. The expanded DNA binding specificity of Tax-CREB and the obligatory role the ternary Tax-CREB-DNA complex plays in transactivation reveal a novel mechanism for regulating the transcriptional activity of leucine zipper proteins like CREB.

Spectral-element simulations of wave propagation in complex exploration-industry models: Mesh generation and forward simulations

NASA Astrophysics Data System (ADS)

Nissen-Meyer, T.; Luo, Y.; Morency, C.; Tromp, J.

2008-12-01

Seismic-wave propagation in exploration-industry settings has seen major research and development efforts for decades, yet large-scale applications have often been limited to 2D or 3D finite-difference, (visco- )acoustic wave propagation due to computational limitations. We explore the possibility of including all relevant physical signatures in the wavefield using the spectral- element method (SPECFEM3D, SPECFEM2D), thereby accounting for acoustic, (visco-)elastic, poroelastic, anisotropic wave propagation in meshes which honor all crucial discontinuities. Mesh design is the crux of the problem, and we use CUBIT (Sandia Laboratories) to generate unstructured quadrilateral 2D and hexahedral 3D meshes for these complex background models. While general hexahedral mesh generation is an unresolved problem, we are able to accommodate most of the relevant settings (e.g., layer-cake models, salt bodies, overthrusting faults, and strong topography) with respectively tailored workflows. 2D simulations show localized, characteristic wave effects due to these features that shall be helpful in designing survey acquisition geometries in a relatively economic fashion. We address some of the fundamental issues this comprehensive modeling approach faces regarding its feasibility: Assessing geological structures in terms of the necessity to honor the major structural units, appropriate velocity model interpolation, quality control of the resultant mesh, and computational cost for realistic settings up to frequencies of 40 Hz. The solution to this forward problem forms the basis for subsequent 2D and 3D adjoint tomography within this context, which is the subject of a companion paper.

Promoting physical therapists’ of research evidence to inform clinical practice: part 1 - theoretical foundation, evidence, and description of the PEAK program

PubMed Central

2014-01-01

Background There is a need for theoretically grounded and evidence-based interventions that enhance the use of research evidence in physical therapist practice. This paper and its companion paper introduce the Physical therapist-driven Education for Actionable Knowledge translation (PEAK) program, an educational program designed to promote physical therapists’ integration of research evidence into clinical decision-making. The pedagogical foundations for the PEAK educational program include Albert Bandura’s social cognitive theory and Malcolm Knowles’s adult learning theory. Additionally, two complementary frameworks of knowledge translation, the Promoting Action on Research Implementation in Health Services (PARiHS) and Knowledge to Action (KTA) Cycle, were used to inform the organizational elements of the program. Finally, the program design was influenced by evidence from previous attempts to facilitate the use of research in practice at the individual and organizational levels. Discussion The 6-month PEAK program consisted of four consecutive and interdependent components. First, leadership support was secured and electronic resources were acquired and distributed to participants. Next, a two-day training workshop consisting of didactic and small group activities was conducted that addressed the five steps of evidence based practice. For five months following the workshop, participants worked in small groups to review and synthesize literature around a group-selected area of common clinical interest. Each group contributed to the generation of a “Best Practices List” - a list of locally generated, evidence-based, actionable behaviors relevant to the groups’ clinical practice. Ultimately, participants agreed to implement the Best Practices List in their clinical practice. Summary This, first of two companion papers, describes the underlying pedagogical theories, knowledge translation frameworks, and research evidence used to derive the PEAK program – an educational program designed to promote the use of research evidence to inform physical therapist practice. The four components of the program are described in detail. The companion paper reports the results of a mixed methods feasibility analysis of this complex educational intervention. PMID:24965501

Behavior of restriction–modification systems as selfish mobile elements and their impact on genome evolution

PubMed Central

Kobayashi, Ichizo

2001-01-01

Restriction–modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes. PMID:11557807

Behavior of restriction-modification systems as selfish mobile elements and their impact on genome evolution.

PubMed

Kobayashi, I

2001-09-15

Restriction-modification (RM) systems are composed of genes that encode a restriction enzyme and a modification methylase. RM systems sometimes behave as discrete units of life, like viruses and transposons. RM complexes attack invading DNA that has not been properly modified and thus may serve as a tool of defense for bacterial cells. However, any threat to their maintenance, such as a challenge by a competing genetic element (an incompatible plasmid or an allelic homologous stretch of DNA, for example) can lead to cell death through restriction breakage in the genome. This post-segregational or post-disturbance cell killing may provide the RM complexes (and any DNA linked with them) with a competitive advantage. There is evidence that they have undergone extensive horizontal transfer between genomes, as inferred from their sequence homology, codon usage bias and GC content difference. They are often linked with mobile genetic elements such as plasmids, viruses, transposons and integrons. The comparison of closely related bacterial genomes also suggests that, at times, RM genes themselves behave as mobile elements and cause genome rearrangements. Indeed some bacterial genomes that survived post-disturbance attack by an RM gene complex in the laboratory have experienced genome rearrangements. The avoidance of some restriction sites by bacterial genomes may result from selection by past restriction attacks. Both bacteriophages and bacteria also appear to use homologous recombination to cope with the selfish behavior of RM systems. RM systems compete with each other in several ways. One is competition for recognition sequences in post-segregational killing. Another is super-infection exclusion, that is, the killing of the cell carrying an RM system when it is infected with another RM system of the same regulatory specificity but of a different sequence specificity. The capacity of RM systems to act as selfish, mobile genetic elements may underlie the structure and function of RM enzymes.

Insulin-like growth factor-I increases bone sialoprotein (BSP) expression through fibroblast growth factor-2 response element and homeodomain protein-binding site in the proximal promoter of the BSP gene.

PubMed

Nakayama, Youhei; Nakajima, Yu; Kato, Naoko; Takai, Hideki; Kim, Dong-Soon; Arai, Masato; Mezawa, Masaru; Araki, Shouta; Sodek, Jaro; Ogata, Yorimasa

2006-08-01

Insulin-like growth factor-I (IGF-I) promotes bone formation by stimulating proliferation and differentiation of osteoblasts. Bone sialoprotein (BSP), is thought to function in the initial mineralization of bone, is selectively expressed by differentiated osteoblast. To determine the molecular mechanism of IGF-I regulation of osteogenesis, we analyzed the effects of IGF-I on the expression of BSP in osteoblast-like Saos2 and in rat stromal bone marrow (RBMC-D8) cells. IGF-I (50 ng/ml) increased BSP mRNA levels at 12 h in Saos2 cells. In RBMC-D8 cells, IGF-I increased BSP mRNA levels at 3 h. From transient transfection assays, a twofold increase in transcription by IGF-I was observed at 12 h in pLUC3 construct that included the promoter sequence from -116 to +60. Effect of IGF-I was abrogated by 2-bp mutations in either the FGF2 response element (FRE) or homeodomain protein-binding site (HOX). Gel shift analyses showed that IGF-I increased binding of nuclear proteins to the FRE and HOX elements. Notably, the HOX-protein complex was supershifted by Smad1 antibody, while the FRE-protein complex was shifted by Smad1 and Cbfa1 antibodies. Dlx2 and Dlx5 antibodies disrupted the formation of the FRE- and HOX-protein complexes. The IGF-I effects on the formation of FRE-protein complexes were abolished by tyrosine kinase inhibitor herbimycin A (HA), PI3-kinase/Akt inhibitor LY249002, and MAP kinase kinase inhibitor U0126, while IGF-I effects on HOX-protein complexes were abolished by HA and LY249002. These studies demonstrate that IGF-I stimulates BSP transcription by targeting the FRE and HOX elements in the proximal promoter of BSP gene.

Overcoming regulatory and economic challenges facing pharmacogenomics.

PubMed

Cohen, Joshua P

2012-09-15

The number of personalized medicines and companion diagnostics in use in the United States has gradually increased over the past decade, from a handful of medicines and tests in 2001 to several dozen in 2011. However, the numbers have not reached the potential hoped for when the human genome project was completed in 2001. Significant clinical, regulatory, and economic barriers exist and persist. From a regulatory perspective, therapeutics and companion diagnostics are ideally developed simultaneously, with the clinical significance of the diagnostic established using data from the clinical development program of the corresponding therapeutic. Nevertheless, this is not (yet) happening. Most personalized medicines are personalized post hoc, that is, a companion diagnostic is developed separately and approved after the therapeutic. This is due in part to a separate and more complex regulatory process for diagnostics coupled with a lack of clear regulatory guidance. More importantly, payers have placed restrictions on reimbursement of personalized medicines and their companion diagnostics, given the lack of evidence on the clinical utility of many tests. To achieve increased clinical adoption of diagnostics and targeted therapies through more favorable reimbursement and incorporation in clinical practice guidelines, regulators will need to provide unambiguous guidance and manufacturers will need to bring more and better clinical evidence to the market place. Copyright © 2012 Elsevier B.V. All rights reserved.

HIP 10725: The first solar twin/analogue field blue straggler

NASA Astrophysics Data System (ADS)

Schirbel, Lucas; Meléndez, Jorge; Karakas, Amanda I.; Ramírez, Iván; Castro, Matthieu; Faria, Marcos A.; Lugaro, Maria; Asplund, Martin; Tucci Maia, Marcelo; Yong, David; Howes, Louise; do Nascimento, José D.

2015-12-01

Context. Blue stragglers are easy to identify in globular clusters, but are much harder to identify in the field. Here we present the serendipitous discovery of one field blue straggler, HIP 10725, that closely matches the Sun in mass and age, but with a metallicity slightly lower than solar. Aims: We characterise the solar twin/analogue HIP 10725 to assess whether this star is a blue straggler. Methods: We employed spectra with high resolution (R ~ 105) and high signal-to-noise ratio (330) obtained with UVES at the VLT to perform a differential abundance analysis of the solar analogue HIP 10725. Radial velocities obtained by other instruments were also used to check for binarity. We also studied its chromospheric activity, age, and rotational velocity. Results: HIP 10725 is severely depleted in beryllium ([ Be/H ] ≤ -1.2 dex) for its stellar parameters and age. The abundances relative to solar of the elements with Z ≤ 30 show a correlation with condensation temperature, and the neutron capture elements produced by the s-process are greatly enhanced, while the r-process elements seem normal. We found its projected rotational velocity (vsini = 3.3 ± 0.1 km s-1) to be significantly higher than solar and incompatible with its isochrone-derived age. Radial velocity monitoring shows that the star has a binary companion. Conclusions: Based on the high s-process element enhancements and low beryllium abundance, we suggest that HIP 10725 has been polluted by mass transfer from an AGB star that probably had an initial mass of about 2 M⊙. The radial velocity variations suggest the presence of an unseen binary companion, probably the remnant of a former AGB star. Isochrones predict a solar-age star, but this disagrees with the high projected rotational velocity and high chromospheric activity. We conclude that HIP 10725 is a field blue straggler, rejuvenated by the mass-transfer process of its former AGB companion. Based on observations obtained at the European Southern Observatory (ESO) Very Large Telescope (VLT) at Paranal Observatory, Chile (observing programs 083.D-0871, 082.C-0446, 093.D-0807), and complemented with observations taken at the Observatório Pico dos Dias (OPD), Brazil (program OP2014A-011).Appendix A is available in electronic form at http://www.aanda.org

The cellular transcription factor CREB corresponds to activating transcription factor 47 (ATF-47) and forms complexes with a group of polypeptides related to ATF-43.

PubMed

Hurst, H C; Masson, N; Jones, N C; Lee, K A

1990-12-01

Promoter elements containing the sequence motif CGTCA are important for a variety of inducible responses at the transcriptional level. Multiple cellular factors specifically bind to these elements and are encoded by a multigene family. Among these factors, polypeptides termed activating transcription factor 43 (ATF-43) and ATF-47 have been purified from HeLa cells and a factor referred to as cyclic AMP response element-binding protein (CREB) has been isolated from PC12 cells and rat brain. We demonstrated that CREB and ATF-47 are identical and that CREB and ATF-43 form protein-protein complexes. We also found that the cis requirements for stable DNA binding by ATF-43 and CREB are different. Using antibodies to ATF-43 we have identified a group of polypeptides (ATF-43) in the size range from 40 to 43 kDa. ATF-43 polypeptides are related by their reactivity with anti-ATF-43, DNA-binding specificity, complex formation with CREB, heat stability, and phosphorylation by protein kinase A. Certain cell types vary in their ATF-43 complement, suggesting that CREB activity is modulated in a cell-type-specific manner through interaction with ATF-43. ATF-43 polypeptides do not appear simply to correspond to the gene products of the ATF multigene family, suggesting that the size of the ATF family at the protein level is even larger than predicted from cDNA-cloning studies.

ComplexQuant: high-throughput computational pipeline for the global quantitative analysis of endogenous soluble protein complexes using high resolution protein HPLC and precision label-free LC/MS/MS.

PubMed

Wan, Cuihong; Liu, Jian; Fong, Vincent; Lugowski, Andrew; Stoilova, Snejana; Bethune-Waddell, Dylan; Borgeson, Blake; Havugimana, Pierre C; Marcotte, Edward M; Emili, Andrew

2013-04-09

The experimental isolation and characterization of stable multi-protein complexes are essential to understanding the molecular systems biology of a cell. To this end, we have developed a high-throughput proteomic platform for the systematic identification of native protein complexes based on extensive fractionation of soluble protein extracts by multi-bed ion exchange high performance liquid chromatography (IEX-HPLC) combined with exhaustive label-free LC/MS/MS shotgun profiling. To support these studies, we have built a companion data analysis software pipeline, termed ComplexQuant. Proteins present in the hundreds of fractions typically collected per experiment are first identified by exhaustively interrogating MS/MS spectra using multiple database search engines within an integrative probabilistic framework, while accounting for possible post-translation modifications. Protein abundance is then measured across the fractions based on normalized total spectral counts and precursor ion intensities using a dedicated tool, PepQuant. This analysis allows co-complex membership to be inferred based on the similarity of extracted protein co-elution profiles. Each computational step has been optimized for processing large-scale biochemical fractionation datasets, and the reliability of the integrated pipeline has been benchmarked extensively. This article is part of a Special Issue entitled: From protein structures to clinical applications. Copyright © 2012 Elsevier B.V. All rights reserved.

Identification of alpha-enolase as a nuclear DNA-binding protein in the zona fasciculata but not the zona reticularis of the human adrenal cortex.

PubMed

Wang, Weiye; Wang, Lishan; Endoh, Akira; Hummelke, Geoffrey; Hawks, Christina L; Hornsby, Peter J

2005-01-01

In order to establish whether there are differences in DNA-binding proteins between zona fasciculata (ZF) and zona reticularis (ZR) cells of the human adrenal cortex, we prepared nuclear extracts from separated ZF and ZR cells. The formation of DNA-protein complexes was studied using an element in the first intron of the type I and type II 3beta-hydroxysteroid dehydrogenase genes (HSD3B1 and HSD3B2). Using the element in the HSD3B2 gene as a probe, a complex (C1) was formed with extracts from ZF cells but was formed only at a low level with ZR cell extracts. Another pair of complexes (C2/C3) was formed with both ZF and ZR cell extracts. The ZF-specific protein forming C1 was enriched by column chromatography on DEAE-Sepharose and carboxymethyl-Sepharose. Oligonucleotide competition analysis on the enriched fraction gave results consistent with those obtained on the unfractionated material. A further enrichment was brought about by passing the protein over an oligonucleotide affinity column based on the HSD3B2 element. The protein bound to the column was identified as alpha-enolase by mass spectrometry. Although alpha-enolase is a glycolytic enzyme, it binds to specific DNA sequences and has been found to be present in nuclei of various cell types. We performed immunohistochemistry on sections of adult human adrenal cortex and found alpha-enolase to be located in nuclei of ZF cells but to be predominantly cytoplasmic in ZR cells. Transfection of an alpha-enolase expression vector into NCI-H295R human adrenocortical cells increased HSD3B2 promoter activity, suggesting a possible functional role for this protein in regulation of HSD3B2 expression.

Can and should value-based pricing be applied to molecular diagnostics?

PubMed

Garau, Martina; Towse, Adrian; Garrison, Louis; Housman, Laura; Ossa, Diego

2013-01-01

Current pricing and reimbursement systems for diagnostics are not efficient. Prices for diagnostics are often driven by administrative practices and expected production cost. The purpose of the paper is to discuss how a value-based pricing framework being used to ensure efficient use and price of medicines could also be applied to diagnostics. Diagnostics not only facilitates health gain and cost savings, but also information to guide patients' decisions on interventions and their future 'behaviors'. For value assessment processes we recommend a two-part approach. Companion diagnostics introduced at the launch of the drug should be assessed through new drug assessment processes considering a broad range of value elements and a balanced analysis of diagnostic impacts. A separate diagnostic-dedicated committee using value-based pricing principles should review other diagnostics lying outside the companion diagnostics-and-drug 'at-launch' situation.

Cytoarchitecture and Ultrastructure of Neural Stem Cell Niches and Neurogenic Complexes Maintaining Adult Neurogenesis in the Olfactory Midbrain of Spiny Lobsters, Panulirus argus

PubMed Central

Schmidt, Manfred; Derby, Charles D.

2013-01-01

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a “neurogenic complex.” Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast’s microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. PMID:21523781

Cytoarchitecture and ultrastructure of neural stem cell niches and neurogenic complexes maintaining adult neurogenesis in the olfactory midbrain of spiny lobsters, Panulirus argus.

PubMed

Schmidt, Manfred; Derby, Charles D

2011-08-15

New interneurons are continuously generated in small proliferation zones within neuronal somata clusters in the olfactory deutocerebrum of adult decapod crustaceans. Each proliferation zone is connected to a clump of cells containing one neural stem cell (i.e., adult neuroblast), thus forming a "neurogenic complex." Here we provide a detailed analysis of the cytoarchitecture of neurogenic complexes in adult spiny lobsters, Panulirus argus, based on transmission electron microscopy and labeling with cell-type-selective markers. The clump of cells is composed of unique bipolar clump-forming cells that collectively completely envelop the adult neuroblast and are themselves ensheathed by a layer of processes of multipolar cell body glia. An arteriole is attached to the clump of cells, but dye perfusion experiments show that hemolymph has no access to the interior of the clump of cells. Thus, the clump of cells fulfills morphological criteria of a protective stem cell niche, with clump-forming cells constituting the adult neuroblast's microenvironment together with the cell body glia processes separating it from other tissue components. Bromodeoxyuridine pulse-chase experiments with short survival times suggest that adult neuroblasts are not quiescent but rather cycle actively during daytime. We propose a cell lineage model in which an asymmetrically dividing adult neuroblast repopulates the pool of neuronal progenitor cells in the associated proliferation zone. In conclusion, as in mammalian brains, adult neurogenesis in crustacean brains is fueled by neural stem cells that are maintained by stem cell niches that preserve elements of the embryonic microenvironment and contain glial and vascular elements. Copyright © 2011 Wiley-Liss, Inc.

New High Index Optical Glasses

NASA Astrophysics Data System (ADS)

Blair, Gerald E.; Greco, Edgar J.; DeJager, Donald; Wylot, James M.

1982-02-01

The pioneering work of Charles W. Frederick and George W. Morey on the design by Frederick of an "ideal photographic lens" using hypothetical glasses, and the subsequent discovery and development of rare-element borate glasses by Morey, has been resumed at Eastman Kodak. New ultra-high index, low dispersion crown glasses and companion flint glasses have been developed, based on the needs dictated by lens design studies for novel fast cine' and still camera lenses. These new glasses reduce the number of elements required in a lens while maintaining or improving lens performance. Composition studies leading to these new glasses will be discussed.

Overview of the epidemiology of Giardia

USDA-ARS?s Scientific Manuscript database

Of all species of Giardia, only G. duodenalis infects humans, livestock, companion animals, and wildlife. The similar morphology within G. duodenalis masks genetic and biotypic differences that are large enough for G. duodenalis now to be considered a species complex. Within the G. duodenalis compl...

Synthesis, characterization of α-amino acid Schiff base derived Ru/Pt complexes: Induces cytotoxicity in HepG2 cell via protein binding and ROS generation

NASA Astrophysics Data System (ADS)

Alsalme, Ali; Laeeq, Sameen; Dwivedi, Sourabh; Khan, Mohd. Shahnawaz; Al Farhan, Khalid; Musarrat, Javed; Khan, Rais Ahmad

2016-06-01

We have synthesized two new complexes of platinum (1) and ruthenium (2) with α-amino acid, L-alanine, and 2,3-dihydroxybenzaldehyde derived Schiff base (L). The ligand and both complexes were characterized by using elemental analysis and several other spectroscopic techniques viz; IR, 1H, 13C NMR, EPR, and ESI-MS. Furthermore, the protein-binding ability of synthesized complexes was monitored by UV-visible, fluorescence and circular dichroism techniques with a model protein, human serum albumin (HSA). Both the PtL2 and RuL2 complexes displayed significant binding towards HSA. Also, in vitro cytotoxicity assay for both complexes was carried out on human hepatocellular carcinoma cancer (HepG2) cell line. The results showed concentration-dependent inhibition of cell viability. Moreover, the generation of reactive oxygen species was also evaluated, and results exhibited substantial role in cytotoxicity.

Mixed-ligand Ru(II) complexes with 2,2'-bipyridine and aryldiazo-beta-diketonato auxillary ligands: synthesis, physico-chemical study and antitumour properties.

PubMed

Mishra, Lallan; Yadaw, Ajay K; Bhattacharya, Subrato; Dubey, Santosh K

2005-05-01

The complexes of Ru(II)-2,2'-bipyridyl with substituted diazopentane-2,4-diones (L1H-L5H) were synthesized and characterized by elemental analyses, conductance, FAB (fast atom bombardment) mass and spectral (IR, UV/Vis (UV/visible), NMR) studies. Molecular geometry optimization of the complexes was also made. None of the complexes luminesce. However, facilitated oxidation of Ru(II) to Ru(III) was evidenced from their lower reduction potential data. The ligands and their complexes were tested for their antitumour activity against a variety of tumour cell lines. Though activity is found to vary with the type of tumour cell lines used, yet complex 5 with naphtyldiazopentane-2,4-dione as co-ligand was found to be a potential compound as it showed in general significant activity against all cell lines studied.

Identification of a novel cyclosporin-sensitive element in the human tumor necrosis factor alpha gene promoter

PubMed Central

1993-01-01

Tumor necrosis factor alpha (TNF-alpha), a cytokine with pleiotropic biological effects, is produced by a variety of cell types in response to induction by diverse stimuli. In this paper, TNF-alpha mRNA is shown to be highly induced in a murine T cell clone by stimulation with T cell receptor (TCR) ligands or by calcium ionophores alone. Induction is rapid, does not require de novo protein synthesis, and is completely blocked by the immunosuppressant cyclosporin A (CsA). We have identified a human TNF-alpha promoter element, kappa 3, which plays a key role in the calcium-mediated inducibility and CsA sensitivity of the gene. In electrophoretic mobility shift assays, an oligonucleotide containing kappa 3 forms two DNA protein complexes with proteins that are present in extracts from unstimulated T cells. These complexes appear in nuclear extracts only after T cell stimulation. Induction of the inducible nuclear complexes is rapid, independent of protein synthesis, and blocked by CsA, and thus, exactly parallels the induction of TNF-alpha mRNA by TCR ligands or by calcium ionophore. Our studies indicate that the kappa 3 binding factor resembles the preexisting component of nuclear factor of activated T cells. Thus, the TNF-alpha gene is an immediate early gene in activated T cells and provides a new model system in which to study CsA-sensitive gene induction in activated T cells. PMID:8376940

Nuclear pore complex tethers to the cytoskeleton.

PubMed

Goldberg, Martin W

2017-08-01

The nuclear envelope is tethered to the cytoskeleton. The best known attachments of all elements of the cytoskeleton are via the so-called LINC complex. However, the nuclear pore complexes, which mediate the transport of soluble and membrane bound molecules, are also linked to the microtubule network, primarily via motor proteins (dynein and kinesins) which are linked, most importantly, to the cytoplasmic filament protein of the nuclear pore complex, Nup358, by the adaptor BicD2. The evidence for such linkages and possible roles in nuclear migration, cell cycle control, nuclear transport and cell architecture are discussed. Copyright © 2017. Published by Elsevier Ltd.

Learning Boolean Networks in HepG2 cells using ToxCast High-Content Imaging Data (SOT annual meeting)

EPA Science Inventory

Cells adapt to their environment via homeostatic processes that are regulated by complex molecular networks. Our objective was to learn key elements of these networks in HepG2 cells using ToxCast High-content imaging (HCI) measurements taken over three time points (1, 24, and 72h...

Single Cell Multiplex Protein Measurements through Rare Earth Element Immunolabeling, Laser Capture Microdissection and Inductively Coupled Mass Spectrometry.

PubMed

Liba, Amir; Wanagat, Jonathan

2014-11-01

Complex diseases such as heart disease, stroke, cancer, and aging are the primary causes of death in the US. These diseases cause heterogeneous conditions among cells, conditions that cannot be measured in tissue homogenates and require single cell approaches. Understanding protein levels within tissues is currently assayed using various molecular biology techniques (e.g., Western blots) that rely on milligram to gram quantities of tissue homogenates or immunofluorescent (IF) techniques that are limited by spectral overlap. Tissue homogenate studies lack references to tissue structure and mask signals from individual or rare cellular events. Novel techniques are required to bring protein measurement sensitivity to the single cell level and offer spatiotemporal resolution and scalability. We are developing a novel approach to protein quantification by exploiting the inherently low concentration of rare earth elements (REE) in biological systems. By coupling REE-antibody immunolabeling of cells with laser capture microdissection (LCM) and ICP-QQQ, we are achieving multiplexed protein measurement in histological sections of single cells. This approach will add to evolving single cell techniques and our ability to understand cellular heterogeneity in complex biological systems and diseases.

Study of multi-kilowatt solar arrays for Earth orbit applications

NASA Technical Reports Server (NTRS)

Patterson, R. E.

1983-01-01

A miniaturized Cassegrainian concentrator (MCC) solar array concept is being developed with the objective of significantly reducing the recurring cost of multikilowatt solar arrays. The desired cost reduction is obtained as a result of using very small high efficiency solar cells in conjuction with low cost optics. The MCC single element concept incident slar radiation is reflected rom a primary parabolic reflector to a secondary hyperbolic reflector and finally to a 4 millimeter diameter solar cell. A light catcher cone is used to improve off axis performance. The solar cell is mounted to a heat fin. An element is approximately 13 millimeters thick which permits efficient launch stowage of the concentrator system panels without complex optical component deployments or retractions. The MCC elements are packed in bays within graphite epoxy frames and are electrically connected into appropriate series-parallel circuits. A MCC sngle element with a 21 sq cm entrance aperture and a 20 efficient, 0.25 sq cm gallium arsenide solar cell has the same power output as 30 sq cm of 11-percent efficiency (at 68 C) silicon solar cells.

Providing Feedback, Orientation and Opportunities for Reflection as Key Elements for Successful Mentoring Programs: Reviewing a Program for Future Business Education Teachers

ERIC Educational Resources Information Center

Riebenbauer, Elisabeth; Dreisiebner, Gernot; Stock, Michaela

2017-01-01

The introduction to teaching is critical for novice teachers. Near the end of their master's program, students of Business Education and Development in Austria spend one semester at an assigned school. They are introduced to teaching, while being assisted by peer students, mentoring teachers, and a companion course. Mentors receive special…

New insights into the complex regulation of the glycolytic pathway in Lactococcus lactis. I. Construction and diagnosis of a comprehensive dynamic model.

PubMed

Dolatshahi, Sepideh; Fonseca, Luis L; Voit, Eberhard O

2016-01-01

This article and the companion paper use computational systems modeling to decipher the complex coordination of regulatory signals controlling the glycolytic pathway in the dairy bacterium Lactococcus lactis. In this first article, the development of a comprehensive kinetic dynamic model is described. The model is based on in vivo NMR data that consist of concentration trends in key glycolytic metabolites and cofactors. The model structure and parameter values are identified with a customized optimization strategy that uses as its core the method of dynamic flux estimation. For the first time, a dynamic model with a single parameter set fits all available glycolytic time course data under anaerobic operation. The model captures observations that had not been addressed so far and suggests the existence of regulatory effects that had been observed in other species, but not in L. lactis. The companion paper uses this model to analyze details of the dynamic control of glycolysis under aerobic and anaerobic conditions.

Role of the Conserved Oligomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer Cells

DTIC Science & Technology

2005-05-01

AD Award Number: DAMD17-03-1-0243 TITLE: Role of the Conserved Oligomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast...Glycoprotein Processing in Breast Cancer 5b.GRANTNUMBER Cells DAAD17-03-1-0243 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Sergey N... processing of glycoproteins, exocytosis, protein delivery systems, gene expression, western and northern blot analysis, immunotiuorescence, gradient

On-board monitoring of 2-D spatially-resolved temperatures in cylindrical lithium-ion batteries: Part I. Low-order thermal modelling

NASA Astrophysics Data System (ADS)

Richardson, Robert R.; Zhao, Shi; Howey, David A.

2016-09-01

Estimating the temperature distribution within Li-ion batteries during operation is critical for safety and control purposes. Although existing control-oriented thermal models - such as thermal equivalent circuits (TEC) - are computationally efficient, they only predict average temperatures, and are unable to predict the spatially resolved temperature distribution throughout the cell. We present a low-order 2D thermal model of a cylindrical battery based on a Chebyshev spectral-Galerkin (SG) method, capable of predicting the full temperature distribution with a similar efficiency to a TEC. The model accounts for transient heat generation, anisotropic heat conduction, and non-homogeneous convection boundary conditions. The accuracy of the model is validated through comparison with finite element simulations, which show that the 2-D temperature field (r, z) of a large format (64 mm diameter) cell can be accurately modelled with as few as 4 states. Furthermore, the performance of the model for a range of Biot numbers is investigated via frequency analysis. For larger cells or highly transient thermal dynamics, the model order can be increased for improved accuracy. The incorporation of this model in a state estimation scheme with experimental validation against thermocouple measurements is presented in the companion contribution (http://www.sciencedirect.com/science/article/pii/S0378775316308163)

Modeling of rolling element bearing mechanics. Theoretical manual

NASA Technical Reports Server (NTRS)

Merchant, David H.; Greenhill, Lyn M.

1994-01-01

This report documents the theoretical basis for the Rolling Element Bearing Analysis System (REBANS) analysis code which determines the quasistatic response to external loads or displacement of three types of high-speed rolling element bearings: angular contact ball bearings; duplex angular contact ball bearings; and cylindrical roller bearings. The model includes the effects of bearing ring and support structure flexibility. It is comprised of two main programs: the Preprocessor for Bearing Analysis (PREBAN) which creates the input files for the main analysis program; and Flexibility Enhanced Rolling Element Bearing Analysis (FEREBA), the main analysis program. A companion report addresses the input instructions for and features of the computer codes. REBANS extends the capabilities of the SHABERTH (Shaft and Bearing Thermal Analysis) code to include race and housing flexibility, including such effects as dead band and preload springs.

BHD Tumor Cell Line and Renal Cell Carcinoma Line | NCI Technology Transfer Center | TTC

Cancer.gov

Scientists at the National Cancer Institute  have developed a novel renal cell carcinoma (RCC) cell line designated UOK257, which was derived from the surgical kidney tissue of a patient with hereditary Birt-Hogg-Dube''''(BHD) syndrome and companion cell line UOK257-2 in which FLCN expression has been restored by lentivirus infection. The NCI Urologic Oncology Branch seeks parties interested in licensing or collaborative research to co-develop, evaluate, or commercialize kidney cancer tumor cell lines.

[NADPH-diaphorase activity in digestive system of gastropod molluscs Achatina fulica and Littorina littorea].

PubMed

Zaĭtseva, O V; Kuznetsova, T V; Markosova, T G

2009-01-01

Localization and peculiarities of NO-ergic elements were studied for he first time throughout the entire length of digestive tract of the marine gastropod mollusc Achatina fulica (Prosobranchia) and the terrestrial molusc Littorina littorea (Pulmonata) by using histochemical method of detection of NADPH-diaphorase (NADPHd). NO-ergic cells and fibers were revealed in all parts of the mollusc digestive tract beginning from pharynx. An intensive NADPHd activity was found in many intraepithelial cells of the open type and in their processes in intra- and subepithelial nerve plexuses, single subepithelial neurons, granular connective tissue cells, and numerous nerve fibers among muscle elements of he digestive tract wall as well as in nerves innervating the tract. NADPHd was also present in receptor cells of he oral area and in the central A. fulica ganglia participating in innervation of the digestive tract. The digestive tract NO-ergic system ofA. fulica has a more complex organization that that of L. littorea. In the A. fulica pharynx, stomach, and midgut, directly beneath epithelium, there is revealed a complex system of glomerular structures formed by thin NADPHd-positive nerve fibers coming from the side of epithelium. More superficially under the main groups of muscle elements, small agglomerations of NADPHd-positive neurons are seen, which could be considered as primitive, non-formed microganglia. Peculiarities of distribution and a possible functional role of NO-ergic elements in the digestive tract of molluscs are discussed as compared with other invertebrate and vertebrate animals.

Chemical abundances of primary stars in the Sirius-like binary systems

NASA Astrophysics Data System (ADS)

Kong, X. M.; Zhao, G.; Zhao, J. K.; Shi, J. R.; Kumar, Y. Bharat; Wang, L.; Zhang, J. B.; Wang, Y.; Zhou, Y. T.

2018-05-01

Study of primary stars lying in Sirius-like systems with various masses of white dwarf (WD) companions and orbital separations is one of the key aspects to understand the origin and nature of barium (Ba) stars. In this paper, based on high-resolution and high-S/N spectra, we present systematic analysis of photospheric abundances for 18 FGK primary stars of Sirius-like systems including six giants and 12 dwarfs. Atmospheric parameters, stellar masses, and abundances of 24 elements (C, Na, Mg, Al, Si, S, K, Ca, Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Sr, Y, Zr, Ba, La, Ce, and Nd) are determined homogeneously. The abundance patterns in these sample stars show that most of the elements in our sample follow the behaviour of field stars with similar metallicity. As expected, s-process elements in four known Ba giants show overabundance. A weak correlation was found between anomalies of s-process elemental abundance and orbital separation, suggesting that the orbital separation of the binaries could not be the main constraint to differentiate strong Ba stars from mild Ba stars. Our study shows that the large mass (>0.51 M⊙) of a WD companion in a binary system is not a sufficient condition to form a Ba star, even if the separation between the two components is small. Although not sufficient, it seems to be a necessary condition since Ba stars with lower mass WDs in the observed sample were not found. Our results support that [s/Fe] and [hs/ls] ratios of Ba stars are anti-correlated with the metallicity. However, the different levels of s-process overabundance among Ba stars may not be dominated mainly by the metallicity.

Long-distance transport of Gibberellic Acid Insensitive mRNA in Nicotiana benthamiana

PubMed Central

2013-01-01

Background The Gibberellic Acid (GA) signal is governed by the GAI (Gibberellic Acid Insensitive) repressor, which is characterized by a highly conserved N-terminal DELLA domain. Deletion of the DELLA domain results in constitutive suppression of GA signaling. As the GAI transcript is transportable in phloem elements, a Δ-DELLA GAI (gai) transgenic stock plant can reduce the stature of a scion through transport of gai mRNA from the stock. However, little is known about the characteristics of a scion on a gai stock. Results Arabidopsis Δ-DELLA GAI (gai) was fused with a T7 epitope tag and expressed under the control of a companion cell-specific expression promoter, Commelina yellow mottle virus promoter (CoYMVp), to enhance transport in the phloem. The CoYMVp:Atgai-T7 (CgT) transgenic Nicotiana benthamiana exhibited a dwarf phenotype and lower sensitivity to GA enhancement of shoot stature. A wild-type (WT) scion on a CgT stock contained both Atgai-T7 mRNA and the translated product. Microarray analysis to clarify the effect of the CgT stock on the gene expression pattern in the scion clearly revealed that the WT scions on CgT stocks had fewer genes whose expression was altered in response to GA treatment. An apple rootstock variety, Malus prunifolia, integrating CoYMVp:Atgai moderately reduced the tree height of the apple cultivar scion. Conclusions Our results demonstrate that Atgai mRNA can move from companion cells to sieve tubes and that the translated product remains at the sites to which it is transported, resulting in attenuation of GA responses by reducing the expression of many genes. The induction of semi-dwarfism in an apple cultivar on root stock harbouring Atgai suggests that long-distance transport of mRNA from grafts would be applicable to horticulture crops. PMID:24144190

Co-operative intra-protein structural response due to protein-protein complexation revealed through thermodynamic quantification: study of MDM2-p53 binding

NASA Astrophysics Data System (ADS)

Samanta, Sudipta; Mukherjee, Sanchita

2017-10-01

The p53 protein activation protects the organism from propagation of cells with damaged DNA having oncogenic mutations. In normal cells, activity of p53 is controlled by interaction with MDM2. The well understood p53-MDM2 interaction facilitates design of ligands that could potentially disrupt or prevent the complexation owing to its emergence as an important objective for cancer therapy. However, thermodynamic quantification of the p53-peptide induced structural changes of the MDM2-protein remains an area to be explored. This study attempts to understand the conformational free energy and entropy costs due to this complex formation from the histograms of dihedral angles generated from molecular dynamics simulations. Residue-specific quantification illustrates that, hydrophobic residues of the protein contribute maximum to the conformational thermodynamic changes. Thermodynamic quantification of structural changes of the protein unfold the fact that, p53 binding provides a source of inter-element cooperativity among the protein secondary structural elements, where the highest affected structural elements (α2 and α4) found at the binding site of the protein affects faraway structural elements (β1 and Loop1) of the protein. The communication perhaps involves water mediated hydrogen bonded network formation. Further, we infer that in inhibitory F19A mutation of P53, though Phe19 is important in the recognition process, it has less prominent contribution in the stability of the complex. Collectively, this study provides vivid microscopic understanding of the interaction within the protein complex along with exploring mutation sites, which will contribute further to engineer the protein function and binding affinity.

A HLA class I cis-regulatory element whose activity can be modulated by hormones.

PubMed

Sim, B C; Hui, K M

1994-12-01

To elucidate the basis of the down-regulation in major histocompatibility complex (MHC) class I gene expression and to identify possible DNA-binding regulatory elements that have the potential to interact with class I MHC genes, we have studied the transcriptional regulation of class I HLA genes in human breast carcinoma cells. A 9 base pair (bp) negative cis-regulatory element (NRE) has been identified using band-shift assays employing DNA sequences derived from the 5'-flanking region of HLA class I genes. This 9-bp element, GTCATGGCG, located within exon I of the HLA class I gene, can potently inhibit the expression of a heterologous thymidine kinase (TK) gene promoter and the HLA enhancer element. Furthermore, this regulatory element can exert its suppressive function in either the sense or anti-sense orientation. More interestingly, NRE can suppress dexamethasone-mediated gene activation in the context of the reported glucocorticoid-responsive element (GRE) in MCF-7 cells but has no influence on the estrogen-mediated transcriptional activation of MCF-7 cells in the context of the reported estrogen-responsive element (ERE). Furthermore, the presence of such a regulatory element within the HLA class I gene whose activity can be modulated by hormones correlates well with our observation that the level of HLA class I gene expression can be down-regulated by hormones in human breast carcinoma cells. Such interactions between negative regulatory elements and specific hormone trans-activators are novel and suggest a versatile form of transcriptional control.

An eccentric companion at the edge of the brown dwarf desert orbiting the 2.4 M⊙ giant star HIP 67537

NASA Astrophysics Data System (ADS)

Jones, M. I.; Brahm, R.; Wittenmyer, R. A.; Drass, H.; Jenkins, J. S.; Melo, C. H. F.; Vos, J.; Rojo, P.

2017-06-01

We report the discovery of a substellar companion around the giant star HIP 67537. Based on precision radial velocity measurements from CHIRON and FEROS high-resolution spectroscopic data, we derived the following orbital elements for HIP 67537 b: mb sin I = 11.1+0.4-1.1Mjup, a =4.9+0.14-0.13 AU and e = 0.59+0.05-0.02 . Considering random inclination angles, this object has ≳65% probability to be above the theoretical deuterium-burning limit, thus it is one of the few known objects in the planet to brown-dwarf (BD) transition region. In addition, we analyzed the Hipparcos astrometric data of this star, from which we derived a minimum inclination angle for the companion of 2 deg. This value corresponds to an upper mass limit of 0.3 M⊙, therefore the probability that HIP 67537 b is stellar in nature is ≲7%. The large mass of the host star and the high orbital eccentricity makes HIP 67537 b a very interesting and rare substellar object. This is the second candidate companion in the brown dwarf desert detected in the sample of intermediate-mass stars targeted by the EXoPlanets aRound Evolved StarS (EXPRESS) radial velocity program, which corresponds to a detection fraction of f = +2.0-0.5 %. This value is larger than the fraction observed in solar-type stars, providing new observational evidence of an enhanced formation efficiency of massive substellar companions in massive disks. Finally, we speculate about different formation channels for this object. Based on observations collected at La Silla - Paranal Observatory under programs ID's 085.C-0557, 087.C.0476, 089.C-0524, 090.C-0345 and through the Chilean Telescope Time under programs ID's CN-12A-073, CN-12B-047, CN-13A-111, CN-2013B-51, CN-2014A-52, CN-15A-48, CN-15B-25 and CN-16A-13.

The putative Agrobacterium transcriptional activator-like virulence protein VirD5 may target T-complex to prevent the degradation of coat proteins in the plant cell nucleus.

PubMed

Wang, Yafei; Peng, Wei; Zhou, Xu; Huang, Fei; Shao, Lingyun; Luo, Meizhong

2014-09-01

Agrobacterium exports at least five virulence proteins (VirE2, VirE3, VirF, VirD2, VirD5) into host cells and hijacks some host plant factors to facilitate its transformation process. Random DNA binding selection assays (RDSAs), electrophoretic mobility shift assays (EMSAs) and yeast one-hybrid systems were used to identify protein-bound DNA elements. Bimolecular fluorescence complementation, glutathione S-transferase pull-down and yeast two-hybrid assays were used to detect protein interactions. Protoplast transformation, coprecipitation, competitive binding and cell-free degradation assays were used to analyze the relationships among proteins. We found that Agrobacterium VirD5 exhibits transcriptional activation activity in yeast, is located in the plant cell nucleus, and forms homodimers. A specific VirD5-bound DNA element designated D5RE (VirD5 response element) was identified. VirD5 interacted directly with Arabidopsis VirE2 Interacting Protein 1 (AtVIP1). However, the ternary complex of VirD5-AtVIP1-VirE2 could be detected, whereas that of VirD5-AtVIP1-VBF (AtVIP1 Binding F-box protein) could not. We demonstrated that VirD5 competes with VBF for binding to AtVIP1 and stabilizes AtVIP1 and VirE2 in the cell-free degradation system. Our results indicated that VirD5 may act as both a transcriptional activator-like effector to regulate host gene expression and a protector preventing the coat proteins of the T-complex from being quickly degraded by the host's ubiquitin proteasome system (UPS). © 2014 The Authors. New Phytologist © 2014 New Phytologist Trust.

A Micromechanics Finite Element Model for Studying the Mechanical Behavior of Spray-On Foam Insulation (SOFI)

NASA Technical Reports Server (NTRS)

Ghosn, Louis J.; Sullivan, Roy M.; Lerch, Bradley A.

2006-01-01

A micromechanics model has been constructed to study the mechanical behavior of spray-on foam insulation (SOFI) for the external tank. The model was constructed using finite elements representing the fundamental repeating unit of the SOFI microstructure. The details of the micromechanics model were based on cell observations and measured average cell dimensions discerned from photomicrographs. The unit cell model is an elongated Kelvin model (fourteen-sided polyhedron with 8 hexagonal and six quadrilateral faces), which will pack to a 100% density. The cell faces and cell edges are modeled using three-dimensional 20-node brick elements. Only one-eighth of the cell is modeled due to symmetry. By exercising the model and correlating the results with the macro-mechanical foam behavior obtained through material characterization testing, the intrinsic stiffness and Poisson s Ratio of the polymeric cell walls and edges are determined as a function of temperature. The model is then exercised to study the unique and complex temperature-dependent mechanical behavior as well as the fracture initiation and propagation at the microscopic unit cell level.

General Methodology Combining Engineering Optimization of Primary HVAC and R Plants with Decision Analysis Methods--Part II: Uncertainty and Decision Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jiang, Wei; Reddy, T. A.; Gurian, Patrick

2007-01-31

A companion paper to Jiang and Reddy that presents a general and computationally efficient methodology for dyanmic scheduling and optimal control of complex primary HVAC&R plants using a deterministic engineering optimization approach.

Numerical Methods of Computational Electromagnetics for Complex Inhomogeneous Systems

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cai, Wei

Understanding electromagnetic phenomena is the key in many scientific investigation and engineering designs such as solar cell designs, studying biological ion channels for diseases, and creating clean fusion energies, among other things. The objectives of the project are to develop high order numerical methods to simulate evanescent electromagnetic waves occurring in plasmon solar cells and biological ion-channels, where local field enhancement within random media in the former and long range electrostatic interactions in the latter are of major challenges for accurate and efficient numerical computations. We have accomplished these objectives by developing high order numerical methods for solving Maxwell equationsmore » such as high order finite element basis for discontinuous Galerkin methods, well-conditioned Nedelec edge element method, divergence free finite element basis for MHD, and fast integral equation methods for layered media. These methods can be used to model the complex local field enhancement in plasmon solar cells. On the other hand, to treat long range electrostatic interaction in ion channels, we have developed image charge based method for a hybrid model in combining atomistic electrostatics and continuum Poisson-Boltzmann electrostatics. Such a hybrid model will speed up the molecular dynamics simulation of transport in biological ion-channels.« less

Debris protection cover assembly for cable connectors

NASA Technical Reports Server (NTRS)

Yovan, Roger D. (Inventor)

1999-01-01

A protective cover assembly for an end of a cable connector having a cable housing that encloses a plurality of connective pins or sockets and that satisfies all requirements for space applications. A connector body flange is formed at the extremity of a cable and is positioned so that it may register with a corresponding connector body flange on the end of a companion cable to which a connection is to be made, one cable end having cable lead pins and the companion cable end having lead sockets with which the pins register. A latch mechanism having a latch housing is received in the connector body flange and a crank connected to a manually rotatable cap actuates a spring-loaded latch element that is engageable with a connector body flange to secure or to release the cover assembly with the simple twisting motion of the cap, thereby simplifying the task of effecting coupling and decoupling of the cable ends.

KEPLER ECLIPSING BINARIES WITH STELLAR COMPANIONS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gies, D. R.; Matson, R. A.; Guo, Z.

2015-12-15

Many short-period binary stars have distant orbiting companions that have played a role in driving the binary components into close separation. Indirect detection of a tertiary star is possible by measuring apparent changes in eclipse times of eclipsing binaries as the binary orbits the common center of mass. Here we present an analysis of the eclipse timings of 41 eclipsing binaries observed throughout the NASA Kepler mission of long duration and precise photometry. This subset of binaries is characterized by relatively deep and frequent eclipses of both stellar components. We present preliminary orbital elements for seven probable triple stars amongmore » this sample, and we discuss apparent period changes in seven additional eclipsing binaries that may be related to motion about a tertiary in a long period orbit. The results will be used in ongoing investigations of the spectra and light curves of these binaries for further evidence of the presence of third stars.« less

A Veterinary Comparative Counseling Elective Featuring Web-based, Student-created, Client Information Sheets.

PubMed

Miller, Jennifer C; Sehgal, Inder

2016-02-25

To design and implement a course in Companion Animal Comparative Counseling that would expose students (N=38) to essential elements of veterinary therapeutics and provide them with the opportunity to apply their knowledge by writing and posting client information sheets (CIS) on an open web site. The elective course was limited to companion animals. Nine different topics were covered over the semester. Class sessions included a didactic component, trivia questions, and field trips. There were 4 major graded assessments: an examination on foundation knowledge, followed by two comparative counseling assessments and evaluation of group-composed CIS. Attendance and participation were also considered. The class learned comparative disease states, how to counsel on common pet prescriptions, where to access informatics about specific veterinary drugs, and how to create their own CIS. As pharmacists, these students may have improved their training in veterinary comparative pharmacy.

A Veterinary Comparative Counseling Elective Featuring Web-based, Student-created, Client Information Sheets

PubMed Central

Miller, Jennifer C.

2016-01-01

Objective. To design and implement a course in Companion Animal Comparative Counseling that would expose students (N=38) to essential elements of veterinary therapeutics and provide them with the opportunity to apply their knowledge by writing and posting client information sheets (CIS) on an open web site. Design. The elective course was limited to companion animals. Nine different topics were covered over the semester. Class sessions included a didactic component, trivia questions, and field trips. There were 4 major graded assessments: an examination on foundation knowledge, followed by two comparative counseling assessments and evaluation of group-composed CIS. Attendance and participation were also considered. Assessment. The class learned comparative disease states, how to counsel on common pet prescriptions, where to access informatics about specific veterinary drugs, and how to create their own CIS. Conclusion. As pharmacists, these students may have improved their training in veterinary comparative pharmacy. PMID:26941441

Completing the Copernican Revolution: The search for other planetary systems

NASA Technical Reports Server (NTRS)

Black, David C.

1995-01-01

The past few decades have witnessed significant advances in our understanding of how stars form, and there has been an associated increase in our knowledge of conditions and phenomena in the early solar system. These have led to the formulation of a paradigm for the origin of the solar system that is sufficiently complete that its basic elements can be tested directly through observations. A simple, but profound, consequence of the paradigm is that most if not all stars should be accompanied by planetary systems. The accuracy of instruments that can be used in such searches has improved to the point that Jupiter-like companions to a number of nearby stars could be detected. However, the results to date are that no other planetary systems have been detected, and the absence of detection is becoming statistically significant, particularly as it relates to the existence of brown dwarf companions to main-sequence stars.

Protostellar Disk Instabilities and the Formation of Substellar Companions

NASA Astrophysics Data System (ADS)

Pickett, Brian K.; Durisen, Richard H.; Cassen, Patrick; Mejia, Annie C.

2000-09-01

Recent numerical simulations of self-gravitating protostellar disks have suggested that gravitational instabilities can lead to the production of substellar companions. In these simulations, the disk is typically assumed to be locally isothermal; i.e., the initial, axisymmetric temperature in the disk remains everywhere unchanged. Such an idealized condition implies extremely efficient cooling for outwardly moving parcels of gas. While we have seen disk disruption in our own locally isothermal simulations of a small, massive protostellar disk, no long-lived companions formed as a result of the instabilities. Instead, thermal and tidal effects and the complex interactions of the disk material prevented permanent condensations from forming, despite the vigorous growth of spiral instabilities. In order to compare our results more directly with those of other authors, we here present three-dimensional evolutions of an older, larger, but less massive protostellar disk. We show that potentially long-lived condensations form only for the extreme of local isothermality, and then only when severe restrictions are placed on the natural tendency of the protostellar disk to expand in response to gravitational instabilities. A more realistic adiabatic evolution leads to vertical and radial expansion of the disk but no clump formation. We conclude that isothermal disk calculations cannot demonstrate companion formation by disk fragmentation but only suggest it at best. It will be necessary in future numerical work on this problem to treat the disk thermodynamics more realistically.

Intellectual property considerations for molecular diagnostic development with emphasis on companion diagnostics.

PubMed

Glorikian, Harry; Warburg, Richard Jeremy; Moore, Kelly; Malinowski, Jennifer

2018-02-01

The development of molecular diagnostics is a complex endeavor, with multiple regulatory pathways to consider and numerous approaches to development and commercialization. Companion diagnostics, devices which are "essential for the safe and effective use of a corresponding drug or diagnostic product" (see U.S. Food & Drug Administration, In Vitro Diagnostics - Companion Diagnostics, U.S. Dept. of Health & Human Services(2016), available at https://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm407297.htm ) and complementary diagnostics, which are more broadly associated with a class of drug, are becoming increasingly important as integral components of the implementation of precision medicine. Areas covered: The following article will highlight the intellectual property ('IP') considerations pertinent to molecular diagnostics development with special emphasis on companion diagnostics. Expert opinion/commentary Summary: For all molecular diagnostics, intellectual property (IP) concerns are of paramount concern, whether the device will be marketed only in the United States or abroad. Taking steps to protect IP at each stage of product development is critical to optimize profitability of a diagnostic product. Also the legal framework around IP protection of diagnostic technologies has been changing over the previous few years and can be expected to continue to change in the foreseeable near future, thus, a comprehensive IP strategy should take into account the fact that changes in the law can be expected.

Chapter 4. Cytomechanics of hair basics of the mechanical stability.

PubMed

Popescu, Crisan; Höcker, Hartwig

2009-01-01

Hair is a complex "cornified" multicellular tissue composed of cuticle and cortex cells mechanically acting as a whole. The cuticle cells overlap and cortex cells interdigitate, all cells being composed of different morphological elements and separated by the cell membrane complex (CMC). The CMC and the morphological elements of the cortex cells, the macrofibrils, composed of microfibrils or intermediate filaments (IFs), and the intermacrofibrillar and intermicrofibrillar cement or the amorphous matrix material determine the mechanical properties of hair. The IFs consist of alpha-keratin molecules being arranged in a sophisticated way of two parallel monomers and antiparallel and shifted dimers rationalized by the amino acid composition and sequence. The mechanical properties of hair result from mechanical interlocking effects, hydrophobic effects, hydrogen bridges, Coulombic interactions, and (covalent) isodipeptide and, in particular, disulfide bridges on a molecular level. The mechanical models applied to hair are based on a simple two-component system, the microfibril/matrix structure. An important regime of the stress-strain curve is the transition of the molecules of the microfibrils from the alpha-helical to the beta-sheet structure. Due to the longitudinal orientation of the IF molecules the longitudinal swelling of the fibers in water is negligible, the radial swelling, however, is substantial.

The HUSH complex cooperates with TRIM28 to repress young retrotransposons and new genes.

PubMed

Robbez-Masson, Luisa; Tie, Christopher H C; Conde, Lucia; Tunbak, Hale; Husovsky, Connor; Tchasovnikarova, Iva A; Timms, Richard T; Herrero, Javier; Lehner, Paul J; Rowe, Helen M

2018-05-04

Retrotransposons encompass half of the human genome and contribute to the formation of heterochromatin, which provides nuclear structure and regulates gene expression. Here, we asked if the human silencing hub (HUSH) complex is necessary to silence retrotransposons and whether it collaborates with TRIM28 and the chromatin remodeler ATRX at specific genomic loci. We show that the HUSH complex contributes to de novo repression and DNA methylation of a SVA retrotransposon reporter. By using naïve vs. primed mouse pluripotent stem cells, we reveal a critical role for the HUSH complex in naïve cells, implicating it in programming epigenetic marks in development. While the HUSH component FAM208A binds to endogenous retroviruses (ERVs) and long interspersed element-1s (LINE-1s or L1s), it is mainly required to repress evolutionarily young L1s (mouse-specific lineages less than 5 million years old). TRIM28, in contrast, is necessary to repress both ERVs and young L1s. Genes co-repressed by TRIM28 and FAM208A are evolutionarily young, or exhibit tissue-specific expression, are enriched in young L1s and display evidence for regulation through LTR promoters. Finally, we demonstrate that the HUSH complex is also required to repress L1 elements in human cells. Overall, these data indicate that the HUSH complex and TRIM28 co-repress young retrotransposons and new genes rewired by retrotransposon non-coding DNA. Published by Cold Spring Harbor Laboratory Press.

Molecular Analysis of Motility in Metastatic Mammary Adenocarcinoma Cells

DTIC Science & Technology

1996-09-01

elements of epidermoid carcinoma (A43 1) cells. J. Cell. Biol. 103: 87-94 Winkler, M. (1988). Translational regulation in sea urchin eggs: a complex...and Methods. Error bars show SEM . Figure 2. Rhodamine-actin polymerizes preferentially at the tips of lamellipods in EGF- stimulated cells. MTLn3...lamellipods. B) rhodamine-actin intensity at the cell center. Data for each time point is the average and SEM of 15 different cells. Images A and B

Mass balance of metal species in supercritical fluid extraction using sodium diethyldithiocarbamate and dibutylammonium dibutyldithiocarbamate.

PubMed

Wang, Joanna Shaofen; Chiu, Kong-Hwa

2006-03-01

The objective of this work is to track the amount of metal complexes distributed in the extraction cell, collection vial, and tubing used in supercritical fluid extraction (SFE) systems after progressive removal of metal ions in supercritical carbon dioxide (SC-CO2). Sodium diethyldithiocarbamate (NaDDC) and dibutylammonium dibutyldithiocarbamate (DBDC) ligands were used to form complexes with Cd, Cu, Pb, and Zn and CO(2)/5% methanol as a supercritical fluid. The mass balance of metal complexes were obtained before and after extraction, and metals in different locations in the system were flushed out using an organic solvent and nitric acid (HNO3). These results infer that the stability constant (beta) of the metal-ligand complex has a strong correlation with SFE. Because of the composition of the stainless-steel cell, Fe, Cr, and Ni or other trace elements in the cell might interfere with the mass balance of metal complexes in SFE due to an exchange mechanism taking place between the cell and the sample.

Compartmentation of metals in foliage of Populus tremula grown on soils with mixed contamination. II. Zinc binding inside leaf cell organelles.

PubMed

Vollenweider, Pierre; Bernasconi, Petra; Gautschi, Hans-Peter; Menard, Terry; Frey, Beat; Günthardt-Goerg, Madeleine S

2011-01-01

The phytoextraction potential of plants for removing heavy metals from polluted soils is determined by their capacity to store contaminants in aboveground organs and complex them safely. In this study, the metal compartmentation, elemental composition of zinc deposits and zinc complexation within leaves from poplars grown on soil with mixed metal contamination was analysed combining several histochemical and microanalytical approaches. Zinc was the only heavy metal detected and was stored in several organelles in the form of globoid deposits showing β-metachromasy. It was associated to oxygen anions and different cations, noteworthy phosphorous. The deposit structure, elemental composition and element ratios indicated that zinc was chelated by phytic acid ligands. Maturation processes in vacuolar vs. cytoplasmic deposits were suggested by differences in size and amounts of complexed zinc. Hence, zinc complexation by phytate contributed to metal detoxification and accumulation in foliage but could not prevent toxicity reactions therein. Copyright © 2010 Elsevier Ltd. All rights reserved.

Anatomy of a new B-cell-specific enhancer.

PubMed Central

Koch, W; Benoist, C; Mathis, D

1989-01-01

The major histocompatibility complex class II molecules, like the immunoglobulins, are prominent B-lymphocyte markers. Herein, we describe a B-cell-specific enhancer associated with the murine class II gene, Ek alpha. This enhancer has a complex anatomy that suggests interactions between remotely spaced elements. Of particular interest is the finding that two CCAAT boxes spaced one kilobase apart are important for enhancer activity. Somewhat surprisingly, the E alpha and immunoglobulin enhancers seem to show little resemblance. Images PMID:2467189

DNA/RNA binding and anticancer/antimicrobial activities of polymer-copper(II) complexes

NASA Astrophysics Data System (ADS)

Lakshmipraba, Jagadeesan; Arunachalam, Sankaralingam; Riyasdeen, Anvarbatcha; Dhivya, Rajakumar; Vignesh, Sivanandham; Akbarsha, Mohammad Abdulkader; James, Rathinam Arthur

2013-05-01

Water soluble polymer-copper(II) complexes with various degrees of coordination in the polymer chain were synthesized and characterized by elemental analysis, IR, UV-visible and EPR spectra. The DNA/RNA binding behavior of these polymer-copper(II) complexes was examined by UV-visible absorption, emission and circular dichroism spectroscopic methods, and cyclic voltammetry techniques. The binding of the polymer-copper(II) complexes with DNA/RNA was mainly through intercalation but some amount of electrostatic interaction was also observed. This binding capacity increased with the degree of coordination of the complexes. The polymer-copper(II) complex having the highest degree of coordination was subjected to analysis of cytotoxic and antimicrobial properties. The cytotoxicity study indicated that the polymer-copper(II) complexes affected the viability of MCF-7 mammary carcinoma cells, and the cells responded to the treatment with mostly through apoptosis although a few cells succumbed to necrosis. The antimicrobial screening showed activity against some human pathogens.

Cell-Sediment Separation and Elemental Stoichiometries in Extreme Environments

NASA Astrophysics Data System (ADS)

Neveu, M.; Poret-peterson, A. T.; Lee, Z. M.; Anbar, A. D.; Elser, J. J.

2012-12-01

Better understanding of the coupling of major biogeochemical cycles requires knowledge of the cellular elemental composition of key microbes. This is difficult in benthic sediments and mats, because of the contributions of non-living components. We are particularly interested in microbial extremophiles, and therefore sought to determine and interpret bulk and cellular elemental ratios in complex field-collected sediment samples from diverse hot spring ecosystems of Yellowstone National Park (YNP). These samples covered a broad range of temperature, pH, and chemical composition. We also sought to extend stoichiometric analysis to a broader suite of elements, including metals (Fe, Ni, Cu, Zn, Mo, etc.) of biological importance (Sterner and Elser, 2002). To overcome the challenge of rigorously isolating communities from their complex mineral matrices (Havig et al., 2011), we adapted a cell-sediment separation procedure from Amalfitano and Fazi (2008). The method involves chemical (use of a detergent and a chelating agent) and physical methods (stirring, gentle sonication, and gradient centrifugation) to break the microbe-mineral bonds. C and N elemental and isotopic abundances were determined by elemental analysis - isotope ratio - mass spectrometry (EA-IR-MS), while P, Na, Mg, Al, K, Ca, V, Cr, Fe, Co, Ni, Cu, Zn, and Mo contents were determined by inductively coupled plasma - mass spectrometry (ICP-MS). We sought to assess the existence of an "Extended Redfield Ratio" (ERR) for these microbes; that is, to establish the multi-element stoichiometric envelope within which extremophilic microbes must operate. Elemental and isotopic mass balance analyses of cultured E. coli before and after separation showed that our procedure preserved cellular C, N, P, Fe, and trace metal contents: neither loss of these elements (e.g., by cell lysis) nor contamination by reagents were observed. On the other hand, cation-forming elements (Na, Mg, K, Ca), were not conserved. Cell counting by epifluorescence microscopy indicated a cell recovery yield between 6 and 40% in field-collected samples (95% for cultured E. coli). Aluminum, assumed to be non-biological in origin, was used to estimate the extent of mineral contamination of isolated cell communities. These results show that our method is successful at separating microbial cells from sediment collected in extreme environments and preserving them for analysis of a broad suite of elements. Photosynthetic sites yielded much more cell material than hotter, chemosynthetic sites (Cox et al., 2011). We are currently measuring cellular elemental abundances and ratios in samples from relatively low-temperature (25 to 65°C), photosynthetic areas, spanning a wide range of pH (2 to 9.5) and composition. These measurements will be compared to existing datasets on the bulk sediment stoichiometry of these ecosystems, and to previous observations of cellular elemental composition. References: Redfield, A.C. (1934) In Daniel, R.J. [Ed.], James Johnstone Memorial Volume, pp. 176-192, Univ. Press Liverpool. Sterner, R.W., Elser, J.J. (2002) Ecological Stoichiometry Princeton Univ. Press, 441p. Havig, J.R., et al. (2011) JGR 116, G01005. Amalfitano, S., Fazi, S. (2008) J. of Microbiol. Methods 75, 237-243. Cox, A., et al. (2011) Chem. Geol. 280, 344-351.

The long and winding road: transport pathways for amino acids in Arabidopsis seeds.

PubMed

Karmann, Julia; Müller, Benedikt; Hammes, Ulrich Z

2018-03-16

Pathways for assimilates. During their life cycle, plants alternate between a haploid stage, the gametophyte, and a diploid stage, the sporophyte. In higher plants, meiosis generates the gametophyte deeply embedded in the maternal tissue of the flower. The megaspore mother cell undergoes meiosis, and then, the surviving megaspore of the four megaspores produced undergoes mitotic divisions and finally gives rise to the female gametophyte, consisting of the egg cell, two synergids, the central cell, which due to the fusion of two nuclei is diploid (double haploid) in Arabidopsis and most angiosperms and the antipods, whose number is not fixed and varies significantly between species (Yadegari and Drews in Plant Cell 16(Suppl):S133-S141, 2004). The maternal tissues that harbor the female gametophyte and the female gametophyte are referred to as the ovule (Fig. 1). Double fertilization of the egg cell and the central cell by the two generative nuclei of the pollen leads to the diploid embryo and the endosperm, respectively (Hamamura et al. in Curr Opin Plant Biol 15:70-77, 2012). Upon fertilization, the ovule is referred to as the seed. Seeds combine two purposes: to harbor storage compounds for use by the embryo upon germination and to protect the embryo until the correct conditions for germination are encountered. As a consequence, seeds are the plant tissue that is of highest nutritional value and the human diet, by a considerable amount, consists of seeds or seed-derived products. Amino acids are of special interest, because plants serve as the main source for the so-called essential amino acids, that animals cannot synthesize de novo and are therefore often a limiting factor for human growth and development (WHO in Protein and amino acid requirements in human nutrition. WHO technical report series, WHO, Geneva, 2007). The plant embryo needs amino acids for general protein synthesis, and additionally they are used to synthesize storage proteins in the seeds of certain plants, e.g., legumes as a resource to support the growth of the seedling after germination. The support of the embryo depends on transport processes that occur between the mother plant and the seed tissues including the embryo. In this review, we will focus on the processes of unloading amino acids from the phloem and their post-phloem transport. We will further highlight similarities between amino acid transport and the transport of the main assimilate and osmolyte, sucrose. Finally, we will discuss similarities and differences between different plant species in terms of structural aspects but for the molecular aspects we are almost exclusively focusing on Arabidopsis. Fig. 1 Vascularization of the Arabidopsis ovule and seed. Plants expressing ER-localized mCherry under control of the companion cell-specific SUC2 promoter and ER-localized GFP under control of the sieve element marker PD1 as described (Müller et al. 2015) are shown to visualize the phloem in the funiculus and the chalazal regions. a Overview over an ovule. FG: female gametophyte. b A magnification of the region marked by a square in panel a. c Overview over a seed. ES: endosperm; E: embryo. d A magnification of the region marked by a square in panel c. The arrows in b and d point to the terminal companion cell and arrowheads to terminal sieve elements.

Elemental mapping of biological samples using a scanning proton microprobe

NASA Astrophysics Data System (ADS)

Watt, F.; Grime, G. W.

1988-03-01

Elemental mapping using a scanning proton microprobe (SPM) can be a powerful technique for probing trace elements in biology, allowing complex interfaces to be studied in detail, identifying contamination and artefacts present in the specimen, and in certain circumstances obtaining indirect chemical information. Examples used to illustrate the advantages of the technique include the elemental mapping of growing pollen tubes, honey bee brain section, a mouse macrophage cell, human liver section exhibiting primary biliary cirrhosis, and the attack by a mildew fungus on a pea leaf.

A LIKELY CLOSE-IN LOW-MASS STELLAR COMPANION TO THE TRANSITIONAL DISK STAR HD 142527

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biller, Beth; Benisty, Myriam; Chauvin, Gael

2012-07-10

With the uniquely high contrast within 0.''1 ({Delta}mag(L') = 5-6.5 mag) available using Sparse Aperture Masking with NACO at Very Large Telescope, we detected asymmetry in the flux from the Herbig Fe star HD 142527 with a barycenter emission situated at a projected separation of 88 {+-} 5 mas (12.8 {+-} 1.5 AU at 145 pc) and flux ratios in H, K, and L' of 0.016 {+-} 0.007, 0.012 {+-} 0.008, and 0.0086 {+-} 0.0011, respectively (3{sigma} errors), relative to the primary star and disk. After extensive closure-phase modeling, we interpret this detection as a close-in, low-mass stellar companion withmore » an estimated mass of {approx}0.1-0.4 M{sub Sun }. HD 142527 has a complex disk structure, with an inner gap imaged in both the near and mid-IR as well as a spiral feature in the outer disk in the near-IR. This newly detected low-mass stellar companion may provide a critical explanation of the observed disk structure.« less

Supernova SN 2011fe from an exploding carbon-oxygen white dwarf star.

PubMed

Nugent, Peter E; Sullivan, Mark; Cenko, S Bradley; Thomas, Rollin C; Kasen, Daniel; Howell, D Andrew; Bersier, David; Bloom, Joshua S; Kulkarni, S R; Kandrashoff, Michael T; Filippenko, Alexei V; Silverman, Jeffrey M; Marcy, Geoffrey W; Howard, Andrew W; Isaacson, Howard T; Maguire, Kate; Suzuki, Nao; Tarlton, James E; Pan, Yen-Chen; Bildsten, Lars; Fulton, Benjamin J; Parrent, Jerod T; Sand, David; Podsiadlowski, Philipp; Bianco, Federica B; Dilday, Benjamin; Graham, Melissa L; Lyman, Joe; James, Phil; Kasliwal, Mansi M; Law, Nicholas M; Quimby, Robert M; Hook, Isobel M; Walker, Emma S; Mazzali, Paolo; Pian, Elena; Ofek, Eran O; Gal-Yam, Avishay; Poznanski, Dovi

2011-12-14

Type Ia supernovae have been used empirically as 'standard candles' to demonstrate the acceleration of the expansion of the Universe even though fundamental details, such as the nature of their progenitor systems and how the stars explode, remain a mystery. There is consensus that a white dwarf star explodes after accreting matter in a binary system, but the secondary body could be anything from a main-sequence star to a red giant, or even another white dwarf. This uncertainty stems from the fact that no recent type Ia supernova has been discovered close enough to Earth to detect the stars before explosion. Here we report early observations of supernova SN 2011fe in the galaxy M101 at a distance from Earth of 6.4 megaparsecs. We find that the exploding star was probably a carbon-oxygen white dwarf, and from the lack of an early shock we conclude that the companion was probably a main-sequence star. Early spectroscopy shows high-velocity oxygen that slows rapidly, on a timescale of hours, and extensive mixing of newly synthesized intermediate-mass elements in the outermost layers of the supernova. A companion paper uses pre-explosion images to rule out luminous red giants and most helium stars as companions to the progenitor.

DANCING IN THE DARK: NEW BROWN DWARF BINARIES FROM KERNEL PHASE INTERFEROMETRY

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pope, Benjamin; Tuthill, Peter; Martinache, Frantz, E-mail: bjsp@physics.usyd.edu.au, E-mail: p.tuthill@physics.usyd.edu.au, E-mail: frantz@naoj.org

2013-04-20

This paper revisits a sample of ultracool dwarfs in the solar neighborhood previously observed with the Hubble Space Telescope's NICMOS NIC1 instrument. We have applied a novel high angular resolution data analysis technique based on the extraction and fitting of kernel phases to archival data. This was found to deliver a dramatic improvement over earlier analysis methods, permitting a search for companions down to projected separations of {approx}1 AU on NIC1 snapshot images. We reveal five new close binary candidates and present revised astrometry on previously known binaries, all of which were recovered with the technique. The new candidate binariesmore » have sufficiently close separation to determine dynamical masses in a short-term observing campaign. We also present four marginal detections of objects which may be very close binaries or high-contrast companions. Including only confident detections within 19 pc, we report a binary fraction of at least #Greek Lunate Epsilon Symbol#{sub b} = 17.2{sub -3.7}{sup +5.7}%. The results reported here provide new insights into the population of nearby ultracool binaries, while also offering an incisive case study of the benefits conferred by the kernel phase approach in the recovery of companions within a few resolution elements of the point-spread function core.« less

Applicaton of the Calculating Formula for Mean Neutron Exposure on Barium stars

NASA Astrophysics Data System (ADS)

Zhang, F. H.; Zhang, L.; Cui, W. Y.; Zhang, B.

2017-11-01

Latest studies have shown that, in the s-process nucleosynthesis model for the low-mass asymptotic giant branch (AGB) star with (13C) pocket radiative burning during the interpulse period, the distribution of neutron exposures in the nucleosynthesis region can be regarded as an exponential function, and the relation between the mean neutron exposure (τ0) and the model parameters is (τ0} = - Δ τ/ln [q/(1 - r + q)]), in which (Δ τ) is the exposure value of each neutron irradiation, (r) is the overlap factor, and (q) is the mass ratio of the (13C) shell to the He intershell. In this paper the formula is applied to 26 samples of barium stars to test its reliability, and furthermore the neutron exposure nature in the AGB companion stars of 26 barium stars are analyzed. The results show that, the formula is reliable; in the AGB companion stars of 26 barium stars, at least 8 stars definitely have and 12 stars are highly likely to have exponential distribution of neutron exposures, while 4 stars tend to experience single neutron exposure; most of the AGB companion stars may have experienced fewer times of neutron irradiations before the element abundance distribution of the s-process comes to asymptotic condition.

Design of a muscle cell-specific expression vector utilising human vascular smooth muscle alpha-actin regulatory elements.

PubMed

Keogh, M C; Chen, D; Schmitt, J F; Dennehy, U; Kakkar, V V; Lemoine, N R

1999-04-01

The facility to direct tissue-specific expression of therapeutic gene constructs is desirable for many gene therapy applications. We describe the creation of a muscle-selective expression vector which supports transcription in vascular smooth muscle, cardiac muscle and skeletal muscle, while it is essentially silent in other cell types such as endothelial cells, hepatocytes and fibroblasts. Specific transcriptional regulatory elements have been identified in the human vascular smooth muscle cell (VSMC) alpha-actin gene, and used to create an expression vector which directs the expression of genes in cis to muscle cells. The vector contains an enhancer element we have identified in the 5' flanking region of the human VSMC alpha-actin gene involved in mediating VSMC expression. Heterologous pairing experiments have shown that the enhancer does not interact with the basal transcription complex recruited at the minimal SV40 early promoter. Such a vector has direct application in the modulation of VSMC proliferation associated with intimal hyperplasia/restenosis.

The GAPS Programme with HARPS-N at TNG. XV. A substellar companion around a K giant star identified with quasi-simultaneous HARPS-N and GIANO measurements

NASA Astrophysics Data System (ADS)

González-Álvarez, E.; Affer, L.; Micela, G.; Maldonado, J.; Carleo, I.; Damasso, M.; D'Orazi, V.; Lanza, A. F.; Biazzo, K.; Poretti, E.; Gratton, R.; Sozzetti, A.; Desidera, S.; Sanna, N.; Harutyunyan, A.; Massi, F.; Oliva, E.; Claudi, R.; Cosentino, R.; Covino, E.; Maggio, A.; Masiero, S.; Molinari, E.; Pagano, I.; Piotto, G.; Smareglia, R.; Benatti, S.; Bonomo, A. S.; Borsa, F.; Esposito, M.; Giacobbe, P.; Malavolta, L.; Martinez-Fiorenzano, A.; Nascimbeni, V.; Pedani, M.; Rainer, M.; Scandariato, G.

2017-10-01

Context. Identification of planetary companions of giant stars is made difficult because of the astrophysical noise, that may produce radial velocity variations similar to those induced by a companion. On the other hand any stellar signal is wavelength dependent, while signals due to a companion are achromatic. Aims: Our goal is to determine the origin of the Doppler periodic variations observed in the thick disk K giant star TYC 4282-605-1 by HARPS-N at the Telescopio Nazionale Galileo (TNG) and verify if they can be due to the presence of a substellar companion. Methods: Several methods have been used to exclude the stellar origin of the observed signal including detailed analysis of activity indicators and bisector and the analysis of the photometric light curve. Finally we have conducted an observational campaign to monitor the near infrared (NIR) radial velocity with GIANO at the TNG in order to verify whether the NIR amplitude variations are comparable with those observed in the visible. Results: Both optical and NIR radial velocities show consistent variations with a period at 101 days and similar amplitude, pointing to the presence of a companion orbiting the target. The main orbital properties obtained for our giant star with a derived mass of M = 0.97 ± 0.03M⊙ are MPsini = 10.78 ± 0.12MJ; P = 101.54 ± 0.05 days; e = 0.28 ± 0.01 and a = 0.422 ± 0.009 AU. The chemical analysis shows a significant enrichment in the abundance of Na I, Mg I, Al I and Si I while the rest of analyzed elements are consistent with the solar value demonstrating that the chemical composition corresponds with an old K giant (age = 10.1 Gyr) belonging to local thick disk. Conclusions: We conclude that the substellar companion hypothesis for this K giant is the best explanation for the observed periodic radial velocity variation. This study also shows the high potential of multi-wavelength radial velocity observations for the validation of planet candidates. Based on observations collected at the Italian Telescopio Nazionale Galileo (TNG), operated on the island of La Palma by the Fundación Galileo Galilei of the INAF (Istituto Nazionale di Astrofisica) at the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, in the frame of the programme Global Architecture of Planetary Systems (GAPS).

Lifting the Fog on Inequitable Financial Aid Policies: A Companion Brief to "Priced out: How the Wrong Financial Aid Policies Hurt Low-Income Students"

ERIC Educational Resources Information Center

Lynch, Mamie; Engle, Jennifer; Cruz, Jose L.

2011-01-01

A lack of situational awareness has been blamed for many of the most counterproductive decisions American policymakers have made on the battlefield, in response to natural and man-made disasters, and in the design and implementation of domestic policies. There are two key elements such disparate events as the escalation of the Vietnam war, the…

Differentiation in Data Analysis & Probability, PreK-Grade 2: A Content Companion for Ongoing Assessment, Grouping Students, Targeting Instruction, and Adjusting Levels of Cognitive Demand

ERIC Educational Resources Information Center

Taylor-Cox, Jennifer

2008-01-01

This book applies the author's easy but effective differentiation strategies to the data analysis and probability content standard. Taking the foundational elements of differentiation in this book, it helps you: (1) assess students' math abilities quickly and efficiently; (2) group children by need; (3) target instruction to meet every student's…

Accumulation of acidic SK₃ dehydrins in phloem cells of cold- and drought-stressed plants of the Solanaceae.

PubMed

Szabala, Bartosz Mieczyslaw; Fudali, Sylwia; Rorat, Tadeusz

2014-04-01

The role of acidic SK(n) dehydrins in stress tolerance of important crop and model species of the Solanaceae remains unknown. We have previously shown that the acidic SK₃ dehydrin DHN24 from Solanum sogarandinum is constitutively expressed and its expression is associated with cold acclimation. Here we found that DHN24 is specifically localized to phloem cells of vegetative organs of non-acclimated plants. More precise localization of DHN24 revealed that it is primarily found in sieve elements (SEs) and companion cells (CCs) of roots and stems. In cold-acclimated plants, DHN24 is mainly present in all cell types of the phloem. Dhn24 transcripts are also predominantly localized to phloem cells of cold-acclimated stems. Immunoelectron microscopy localized DHN24 to the cytosol and close to organelle membranes of phloem cells, the lumen with phloem protein filaments, parietal cytoplasm of SEs and the nucleoplasm of some nuclei. Cell fractionation experiments revealed that DHN24 was detected in the cytosolic, nuclear and microsomal fractions. We also determined whether homologous members of the acidic subclass dehydrins from Capsicum annuum and Lycopersicon chilense share the characteristics of DHN24. We showed that they are also constitutively expressed, but their protein level is upregulated preferentially by drought stress. Immunofluorescent localization revealed that they are detected in SEs and CCs of unstressed plants and throughout the phloem in drought-stressed plants. These results suggest that one of the primary roles of DHN24 and its homologs may be the protection of the phloem region from adverse effects of abiotic stresses.

The Exoplanet Simple Orbit Fitting Toolbox (ExoSOFT): An Open-source Tool for Efficient Fitting of Astrometric and Radial Velocity Data

NASA Astrophysics Data System (ADS)

Mede, Kyle; Brandt, Timothy D.

2017-03-01

We present the Exoplanet Simple Orbit Fitting Toolbox (ExoSOFT), a new, open-source suite to fit the orbital elements of planetary or stellar-mass companions to any combination of radial velocity and astrometric data. To explore the parameter space of Keplerian models, ExoSOFT may be operated with its own multistage sampling approach or interfaced with third-party tools such as emcee. In addition, ExoSOFT is packaged with a collection of post-processing tools to analyze and summarize the results. Although only a few systems have been observed with both radial velocity and direct imaging techniques, this number will increase, thanks to upcoming spacecraft and ground-based surveys. Providing both forms of data enables simultaneous fitting that can help break degeneracies in the orbital elements that arise when only one data type is available. The dynamical mass estimates this approach can produce are important when investigating the formation mechanisms and subsequent evolution of substellar companions. ExoSOFT was verified through fitting to artificial data and was implemented using the Python and Cython programming languages; it is available for public download at https://github.com/kylemede/ExoSOFT under GNU General Public License v3.

The Star, the Dwarf and the Planet

NASA Astrophysics Data System (ADS)

2006-10-01

Astronomers have detected a new faint companion to the star HD 3651, already known to host a planet. This companion, a brown dwarf, is the faintest known companion of an exoplanet host star imaged directly and one of the faintest T dwarfs detected in the Solar neighbourhood so far. The detection yields important information on the conditions under which planets form. "Such a system is an interesting example that might prove that planets and brown dwarfs can form around the same star", said Markus Mugrauer, lead author of the paper presenting the discovery. ESO PR Photo 39a/06 ESO PR Photo 39a/06 The Companion to HD 3651 HD 3651 is a star slightly less massive than the Sun, located 36 light-years away in the constellation Pisces (the "Fish"). For several years, it has been known to harbour a planet less massive than Saturn, sitting closer to its parent star than Mercury is from the Sun: the planet accomplishes a full orbit in 62 days. Mugrauer and his colleagues first spotted the faint companion in 2003 on images from the 3.8-m United Kingdom Infrared Telescope (UKIRT) in Hawaii. Observations in 2004 and 2006 using ESO's 3.6 m New Technology Telescope (NTT) at La Silla provided the crucial confirmation that the speck of light is not a spurious background star, but indeed a true companion. The newly found companion, HD 3651B, is 16 times further away from HD 3651 than Neptune is from the Sun. HD 3651B is the dimmest directly imaged companion of an exoplanet host star. Furthermore, as it is not detected on the photographic plates of the Palomar All Sky Survey, the companion must be even fainter in the visible spectral range than in the infrared, meaning it is a very cool low-mass sub-stellar object. Comparing its characteristics with theoretical models, the astronomers infer that the object has a mass between 20 and 60 Jupiter masses, and a temperature between 500 and 600 degrees Celsius. It is thus ten times colder and 300 000 less luminous than the Sun. These properties place it in the category of cool T-type brown dwarfs. ESO PR Photo 38b/06 ESO PR Photo 39b/06 The Relative Position of the Companion to HD 3651 "Due to their faintness even in the infrared, these cool T dwarfs are very difficult to find", said Mugrauer. "Only two other brown dwarfs with similar brightness are presently known. Their study will provide important insights into the atmospheric properties of cool sub-stellar objects." More than 170 stars are currently known to host exoplanets. In some cases, these stars were also found to have one or several stellar companions, showing that planet formation can also take place in a dynamically more complex environment than our own Solar System where planet formation occurred around an isolated single star. In 2001, Mugrauer and his colleagues started an observational programme to find out whether exoplanet host stars are single or married. In this programme, known exoplanet host stars are systematically imaged at two different epochs, at least several months apart. True companions can be distinguished from coincidental background objects as only they move together with the stars over time. With this effective search strategy several new companions of exoplanet host stars have been detected. Most of the detected companions are low-mass stars in the same evolutionary state as the Sun. In two cases, however, the astronomers found the companions to be white dwarfs, that is, stars at the end of their life. These intriguing systems bear evidence that planets can even survive the troubled last moments in the life of a nearby star. The planet host star HD 3651 is thus surrounded by two sub-stellar objects. The planet, HD 3651b, is very close, while the newly found brown dwarf companion revolves around the star 1500 times farther away than the planet. This system is the first imaged example that planets and brown dwarfs can form around the same star.

Identification of host factors potentially involved in RTM-mediated resistance during potyvirus long distance movement.

PubMed

Sofer, Luc; Cabanillas, Daniel Garcia; Gayral, Mathieu; Téplier, Rachèle; Pouzoulet, Jérôme; Ducousso, Marie; Dufin, Laurène; Bréhélin, Claire; Ziegler-Graff, Véronique; Brault, Véronique; Revers, Frédéric

2017-07-01

The long distance movement of potyviruses is a poorly understood step of the viral cycle. Only factors inhibiting this process, referred to as "Restricted TEV Movement" (RTM), have been identified in Arabidopsis thaliana. On the virus side, the potyvirus coat protein (CP) displays determinants required for long-distance movement and for RTM-based resistance breaking. However, the potyvirus CP was previously shown not to interact with the RTM proteins. We undertook the identification of Arabidopsis factors which directly interact with either the RTM proteins or the CP of lettuce mosaic virus (LMV). An Arabidopsis cDNA library generated from companion cells was screened with LMV CP and RTM proteins using the yeast two-hybrid system. Fourteen interacting proteins were identified. Two of them were shown to interact with CP and the RTM proteins suggesting that a multiprotein complex could be formed between the RTM proteins and virions or viral ribonucleoprotein complexes. Co-localization experiments in Nicotiana benthamiana showed that most of the viral and cellular protein pairs co-localized at the periphery of chloroplasts which suggests a putative role for plastids in this process.

Genetic diversity of Toxoplasma gondii in animals and humans

USDA-ARS?s Scientific Manuscript database

Toxoplasma gondii is one of the most common parasites of domestic, wild, and companion animals, and it also infects approximately 25% of the world’s human population. T. gondii has a complex life cycle. Sexual development occurs only in the cat gut, while asexual replication and transmission occur i...

A novel E2 box-GATA element modulates Cdc6 transcription during human cells polyploidization

PubMed Central

Vilaboa, Nuria; Bermejo, Rodrigo; Martinez, Pilar; Bornstein, Rafael; Calés, Carmela

2004-01-01

Cdc6 is a key regulator of the strict alternation of S and M phases during the mitotic cell cycle. In mammalian and plant cells that physiologically become polyploid, cdc6 is transcriptionally and post-translationally regulated. We have recently reported that Cdc6 levels are maintained in megakaryoblastic HEL cells, but severely downregulated by ectopic expression of transcriptional repressor Drosophila melanogaster escargot. Here, we show that cdc6 promoter activity is upregulated during megakaryocytic differentiation of HEL endoreplicating cells, and that Escargot interferes with such activation. Transactivation experiments showed that a 1.7 kb region located at 2800 upstream cdc6 transcription initiation site behaved as a potent enhancer in endoreplicating cells only. This activity was mainly dependent on a novel cis-regulatory element composed by an E2 box overlapping a GATA motif. Ectopic Escargot could bind this regulatory element in vitro and endogenous GATA-1 and E2A formed specific complexes in megakaryoblastic cells as well as in primary megakaryocytes. Chromatin Immunoprecipitation analysis revealed that both transcription factors were occupying the E2 box/GATA site in vivo. Altogether, these data suggest that cdc6 expression could be actively maintained during megakaryocytic differentiation through transcriptional mechanisms involving specific cis- and trans-regulatory elements. PMID:15590906

Modeling of rolling element bearing mechanics. Computer program user's manual

NASA Technical Reports Server (NTRS)

Greenhill, Lyn M.; Merchant, David H.

1994-01-01

This report provides the user's manual for the Rolling Element Bearing Analysis System (REBANS) analysis code which determines the quasistatic response to external loads or displacement of three types of high-speed rolling element bearings: angular contact ball bearings, duplex angular contact ball bearings, and cylindrical roller bearings. The model includes the defects of bearing ring and support structure flexibility. It is comprised of two main programs: the Preprocessor for Bearing Analysis (PREBAN) which creates the input files for the main analysis program, and Flexibility Enhanced Rolling Element Bearing Analysis (FEREBA), the main analysis program. This report addresses input instructions for and features of the computer codes. A companion report addresses the theoretical basis for the computer codes. REBANS extends the capabilities of the SHABERTH (Shaft and Bearing Thermal Analysis) code to include race and housing flexibility, including such effects as dead band and preload springs.

Problem-Solving Test: The Mechanism of Action of a Human Papilloma Virus Oncoprotein

ERIC Educational Resources Information Center

Szeberenyi, Jozsef

2009-01-01

Terms to be familiar with before you start to solve the test: human papilloma virus; cervical cancer; oncoproteins; malignant transformation; retinoblastoma protein; cell cycle; quiescent and cycling cells; cyclin/cyclin-dependent kinase (Cdk) complexes; E2F; S-phase genes; enhancer element; proto-oncogenes; tumor suppressor genes; radioactive…

Partitioning heritability by functional annotation using genome-wide association summary statistics.

PubMed

Finucane, Hilary K; Bulik-Sullivan, Brendan; Gusev, Alexander; Trynka, Gosia; Reshef, Yakir; Loh, Po-Ru; Anttila, Verneri; Xu, Han; Zang, Chongzhi; Farh, Kyle; Ripke, Stephan; Day, Felix R; Purcell, Shaun; Stahl, Eli; Lindstrom, Sara; Perry, John R B; Okada, Yukinori; Raychaudhuri, Soumya; Daly, Mark J; Patterson, Nick; Neale, Benjamin M; Price, Alkes L

2015-11-01

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.

Detection of dermatophytes in healthy companion dogs and cats in eastern India.

PubMed

Debnath, C; Mitra, T; Kumar, A; Samanta, I

2016-01-01

In recent times increasing occurrence of dermatophytosis, especially among the school children in eastern India was evidenced along with increased tendency of keeping companion animals such as dogs and cats. This study was undertaken to detect the occurrence of dermatophytes with antifungal susceptibility among the companion animals. A total of 1501 healthy companion animals comprising 1209 dogs and 292 cats belonged to individual owners in and around Kolkata (West Bengal, India) were examined for the evidence of dermatophytosis during 2011-2013. The collected samples were subjected to direct examination by standard KOH mount technique. The samples were inoculated into both Sabouraud dextrose agar (SDA) with 0.05% chloramphenicol and 0.5% cycloheximide and dermatophyte test medium (DTM). Each of the fungal isolate was identified based upon its colony characteristics and hyphal and conidial cells it produced. Antifungal susceptibility of the isolates was tested by broth micro dilution assay using fluconazole, ketoconazole, itraconazole, miconazole, griseofulvin and amphotericin-B antifungals. Among the 1209 samples from dogs and 292 samples from cats, 253 (20.93%) and 109 (37.33%) samples were positive for dermatophytes by direct examination. Three identified species of dermatophytes with predominant occurrence were Microsporum canis, Microsporum gypseum and Trichophyton mentagrophytes. Ketoconazole (0.06-0.5 µgm/ml), itraconazole (0.03-0.5 µgm/ml) and amphotericin-B (0.03-0.5 µgm/ml) showed lowest MIC values against M. canis, T. mentagrophytes and M. gypseum, respectively. This is the first systemic report of dermatophytes in healthy companion animals with large numbers of samples in India.

Characterization, localization, and seasonal changes of the sucrose transporter FeSUT1 in the phloem of Fraxinus excelsior

PubMed Central

Öner-Sieben, Soner; Rappl, Christine; Sauer, Norbert; Stadler, Ruth; Lohaus, Gertrud

2015-01-01

Trees are generally assumed to be symplastic phloem loaders. A typical feature for most wooden species is an open minor vein structure with symplastic connections between mesophyll cells and phloem cells, which allow sucrose to move cell-to-cell through the plasmodesmata into the phloem. Fraxinus excelsior (Oleaceae) also translocates raffinose family oligosaccharides in addition to sucrose. Sucrose concentration was recently shown to be higher in the phloem sap than in the mesophyll cells. This suggests the involvement of apoplastic steps and the activity of sucrose transporters in addition to symplastic phloem-loading processes. In this study, the sucrose transporter FeSUT1 from F. excelsior was analysed. Heterologous expression in baker’s yeast showed that FeSUT1 mediates the uptake of sucrose. Immunohistochemical analyses revealed that FeSUT1 was exclusively located in phloem cells of minor veins and in the transport phloem of F. excelsior. Further characterization identified these cells as sieve elements and possibly ordinary companion cells but not as intermediary cells. The localization and expression pattern point towards functions of FeSUT1 in phloem loading of sucrose as well as in sucrose retrieval. FeSUT1 is most likely responsible for the observed sucrose gradient between mesophyll and phloem. The elevated expression level of FeSUT1 indicated an increased apoplastic carbon export activity from the leaves during spring and late autumn. It is hypothesized that the importance of apoplastic loading is high under low-sucrose conditions and that the availability of two different phloem-loading mechanisms confers advantages for temperate woody species like F. excelsior. PMID:26022258

Engineering Approaches Toward Deconstructing and Controlling the Stem Cell Environment

PubMed Central

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-01-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e. the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to: (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. Here, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering. PMID:22101755

Engineering approaches toward deconstructing and controlling the stem cell environment.

PubMed

Edalat, Faramarz; Bae, Hojae; Manoucheri, Sam; Cha, Jae Min; Khademhosseini, Ali

2012-06-01

Stem cell-based therapeutics have become a vital component in tissue engineering and regenerative medicine. The microenvironment within which stem cells reside, i.e., the niche, plays a crucial role in regulating stem cell self-renewal and differentiation. However, current biological techniques lack the means to recapitulate the complexity of this microenvironment. Nano- and microengineered materials offer innovative methods to (1) deconstruct the stem cell niche to understand the effects of individual elements; (2) construct complex tissue-like structures resembling the niche to better predict and control cellular processes; and (3) transplant stem cells or activate endogenous stem cell populations for regeneration of aged or diseased tissues. In this article, we highlight some of the latest advances in this field and discuss future applications and directions of the use of nano- and microtechnologies for stem cell engineering.

Growing Three-Dimensional Cartilage-Cell Cultures

NASA Technical Reports Server (NTRS)

Spaulding, Glenn F.; Prewett, Tacey L.; Goodwin, Thomas J.

1995-01-01

Process for growing three-dimensional cultures of mammalian cartilage from normal mammalian cells devised. Effected using horizontal rotating bioreactor described in companion article, "Simplified Bioreactor for Growing Mammalian Cells" (MSC-22060). Bioreactor provides quiescent environment with generous supplies of nutrient and oxygen. Initiated with noncartilage cells. Artificially grown tissue resembles that in mammalian cartilage. Potential use in developing therapies for damage to cartilage by joint and back injuries and by such inflammatory diseases as arthritis and temporal-mandibular joint disease. Also used to test nonsteroid anti-inflammation medicines.

Principles and Practices Fostering Inclusive Excellence: Lessons from the Howard Hughes Medical Institute's Capstone Institutions.

PubMed

DiBartolo, Patricia Marten; Gregg-Jolly, Leslie; Gross, Deborah; Manduca, Cathryn A; Iverson, Ellen; Cooke, David B; Davis, Gregory K; Davidson, Cameron; Hertz, Paul E; Hibbard, Lisa; Ireland, Shubha K; Mader, Catherine; Pai, Aditi; Raps, Shirley; Siwicki, Kathleen; Swartz, Jim E

Best-practices pedagogy in science, technology, engineering, and mathematics (STEM) aims for inclusive excellence that fosters student persistence. This paper describes principles of inclusivity across 11 primarily undergraduate institutions designated as Capstone Awardees in Howard Hughes Medical Institute's (HHMI) 2012 competition. The Capstones represent a range of institutional missions, student profiles, and geographical locations. Each successfully directed activities toward persistence of STEM students, especially those from traditionally underrepresented groups, through a set of common elements: mentoring programs to build community; research experiences to strengthen scientific skill/identity; attention to quantitative skills; and outreach/bridge programs to broaden the student pool. This paper grounds these program elements in learning theory, emphasizing their essential principles with examples of how they were implemented within institutional contexts. We also describe common assessment approaches that in many cases informed programming and created traction for stakeholder buy-in. The lessons learned from our shared experiences in pursuit of inclusive excellence, including the resources housed on our companion website, can inform others' efforts to increase access to and persistence in STEM in higher education. © 2016 P. M. DiBartolo, L. Gregg-Jolly, D. Gross, C. A. Manduca, E. Iverson, et al. CBE—Life Sciences Education © 2016 The American Society for Cell Biology. This article is distributed by The American Society for Cell Biology under license from the author(s). It is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The Optical Gravitational Lensing Experiment. Planetary and Low-Luminosity Object Transits in the Fields of Galactic Disk. Results of the 2003 OGLE Observing Campaigns

NASA Astrophysics Data System (ADS)

Udalski, A.; Szymanski, M. K.; Kubiak, M.; Pietrzynski, G.; Soszynski, I.; Zebrun, K.; Szewczyk, O.; Wyrzykowski, L.

2004-12-01

We present results of two observing campaigns conducted by the OGLE-III survey in the 2003 observing season aiming at the detection of new objects with planetary transiting companions. Six fields of 35'x35' each located in the Galactic disk were monitored with high frequency for several weeks in February-July 2003. Additional observations of three of these fields were also collected in the 2004 season. Altogether about 800 and 1500 epochs were collected for the fields of both campaigns, respectively. The search for low depth transits was conducted on about 230 000 stars with photometry better than 15 mmag. It was focused on detection of planetary companions, thus clear non-planetary cases were not included in the final list of selected objects. Altogether we discovered 40 stars with shallow (<=0.05 mag) flat-bottomed transits. In each case several individual transits were observed allowing determination of photometric elements. Additionally, the lower limits on radii of the primary and companion were calculated. From the photometric point of view the new OGLE sample contains many very good candidates for extrasolar transiting planets. However, only the future spectroscopic follow-up observations of the OGLE sample - determination of the amplitude of radial velocity and exclusion of blending possibilities - may allow to confirm their planetary status. In general, the transiting objects may be extrasolar planets, brown dwarfs, M-type dwarfs or fake transits caused by blending. All photometric data of objects with transiting companions discovered during the 2003 campaigns are available to the astronomical community from the OGLE Internet archive.

Intracellular distribution and stability of a luminescent rhenium(i) tricarbonyl tetrazolato complex using epifluorescence microscopy in conjunction with X-ray fluorescence imaging.

PubMed

Wedding, J L; Harris, H H; Bader, C A; Plush, S E; Mak, R; Massi, M; Brooks, D A; Lai, B; Vogt, S; Werrett, M V; Simpson, P V; Skelton, B W; Stagni, S

2017-04-19

Optical epifluorescence microscopy was used in conjunction with X-ray fluorescence imaging to monitor the stability and intracellular distribution of the luminescent rhenium(i) complex fac-[Re(CO) 3 (phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence imaging techniques. X-ray fluorescence also showed that the rhenium complex disrupted the homeostasis of some biologically relevant elements, such as chlorine, potassium and zinc.

Stem cells and regenerative medicine in domestic and companion animals: a multispecies perspective.

PubMed

Gonçalves, N N; Ambrósio, C E; Piedrahita, J A

2014-10-01

Since their original isolation, the majority of the work on embryonic stem cells (ESC) has been carried out in mice. While the mouse is an outstanding model for basic research, it also has considerable limitations for translational work, especially in the area of regenerative medicine. This is due to a combination of factors that include physiological and size differences when compared to humans. In contrast, domestic animal species, such as swine, and companion animal species, such as dogs, provide unique opportunities to develop regenerative medicine protocols that can then be utilized in humans. Unfortunately, at present, the state of knowledge related to, and availability of, ESC from domestic animals vary among species such as pig, horse, dog and cat, and without exception lags significantly behind the mouse and human. It is clear that much still needs to be discovered. The 'stem cell-like' cell lines being reported are still not satisfactorily used in regenerative medicine, due to reasons such as heterogeneity and chromosomal instability. As a result, investigators have searched for alternate source of cells that can be used for regenerative medicine. This approach has uncovered a range of adult stem cells and adult progenitor cells that have utility in both human and veterinary medicine. Here, we review a range of stem cells, from ESC to induced pluripotent stem cells, and discuss their potential application in the field of regenerative medicine. © 2014 Blackwell Verlag GmbH.

Telling Reflections: Teaching Sustainably in a Complex Learning Environment

ERIC Educational Resources Information Center

Prescott, Debbie

2016-01-01

This article examines learning design in a postgraduate preservice teacher setting. The overarching aim was to embed environmentally responsive approaches throughout two companion units for diverse student cohorts. This article reports on a teacher educator self-study in a regional university with extensive online delivery for large units (300-800…

Perspectives on the Teaching of Mathematics. Sixty-Sixth Yearbook [with Companion Guidebook

ERIC Educational Resources Information Center

Rubenstein, Rheta N., Ed.

2004-01-01

Teaching is a complex, ongoing endeavor that involves a myriad of decisions. The National Council of Teachers of Mathematics' (NCTM's) Sixty-Sixth Yearbook is organized around three aspects of teaching: foundations for teaching, the enactment of teaching, and the support of teaching nurtured in preservice education and strengthened throughout a…

A "Bit" of Quantum Mechanics

ERIC Educational Resources Information Center

Oss, Stefano; Rosi, Tommaso

2015-01-01

We have developed an app for iOS-based smart-phones/tablets that allows a 3-D, complex phase-based colorful visualization of hydrogen atom wave functions. Several important features of the quantum behavior of atomic orbitals can easily be made evident, thus making this app a useful companion in introductory modern physics classes. There are many…

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wedding, Jason L.; Harris, Hugh H.; Bader, Christie A.

Optical fluorescence microscopy was used in conjunction with X-ray fluorescence microscopy to monitor the stability and intracellular distribution of the luminescent rhenium(I) complex fac-[Re(CO) 3(phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex, in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence techniques. Furthermore, X-ray fluorescence also showed that the Re-I complex disrupted the homeostasis of some biologically relevant elements,more » such as chlorine, potassium and zinc.« less

Heteroleptic Palladium(II) dithiocarbamates: Synthesis, characterization and in vitro biological screening

NASA Astrophysics Data System (ADS)

Khan, Shahan Zeb; Zia-ur-Rehman; Amir, Muhammad Kashif; Ullah, Imdad; Akhter, M. S.; Bélanger-Gariepy, Francine

2018-03-01

Two new heteroleptic Pd(II) complexes of sodium 4-(2-pyrimidyl)piperazine-1-carbodithioate with tris-p-flourophenylphosphine (1) and tris-p-chlorophenylphosphine (2) were prepared and characterized by elemental analysis, FT-IR, multinuclear NMR {1H, 13C and 31P} and single-crystal X-ray diffraction measurement. In both complexes, Pd exhibit pseudo square planner geometry mediated by SS chelate, P and Cl. In vitro cytotoxicity against five different cancer cell lines using staurosporine as a standard revealed 1 to be more cytotoxic than 2, though both complexes are more active than cisplatin. Subsequent DNA binding studies revealed that non-covalent complex-DNA interaction may be the reason for arresting cancer cell growth. Furthermore, 1 and 2 are potent antioxidant agents.

Synthesis, characterization, and anti-cancer activity of emodin-Mn(II) metal complex.

PubMed

Yang, Li; Tan, Jun; Wang, Bo-Chu; Zhu, Lian-Cai

2014-12-01

To synthesize and characterize a novel metal complex of Mn (II) with emodin, and evaluate its anti-cancer activity. The elemental analyses, IR, UV-vis, atomic absorption spectroscopy, TG-DSC, (1)H NMR, and (13)C NMR data were used to characterize the structure of the complex. The cytotoxicity of the complex against the human cancer cell lines HepG2, HeLa, MCF-7, B16, and MDA-MB-231 was tested by the MTT assay and flow cytometry. Emodin was coordinated with Mn(II) through the 9-C=O and 1-OH, and the general formula of the complex was Mn(II) (emodin)2·2H2O. In studies of the cytotoxicity, the complex exhibited significant activity, and the IC50 values of the complex against five cancer cell lines improved approximately three-fold compared with those of emodin. The complex could induce cell morphological changes, decrease the percentage of viability, and induce G0/G1 phase arrest and apoptosis in cancer cells. The coordination of emodin with Mn(II) can improve its anticancer activity, and the complex Mn(II) (emodin)2·2H2O could be studied further as a promising anticancer drug. Copyright © 2014 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Synthesis, spectroscopic studies, antimicrobial activities and antitumor of a new monodentate V-shaped Schiff base and its transition metal complexes

NASA Astrophysics Data System (ADS)

Ramadan, Ramadan M.; Abu Al-Nasr, Ahmad K.; Noureldeen, Amani F. H.

2014-11-01

Reaction of 4-aminoacetophenone and 4-bromobenzaldehyde in ethanol resulted in the formation of the monodentate V-shaped Schiff base (E)-1-(4-((4-bromo-benzylidene)amino)phenyl)ethanone (L). Interaction of L with different di- and trivalent metal ions revealed disubstituted derivatives. The ligand and its complexes were characterized by elemental analysis, mass, IR and NMR spectrometry. Biological activities of the ligand and complexes against the Escherchia coli and Staphylococcus aureus bacterias, and the two fungus Aspergillus flavus and Candida albicans were screened. The cytotoxicity of the compounds were checked as antitumor agents on liver carcinoma cell line (HepG2). They exhibited in vitro broad range of antitumor activities towards the cell line; the [ZnL2(H2O)2](NO3)2 complex was stronger antitumor towards HepG2 cell line as well as two breast cancer cell lines (MCF7 and T47D) relative to cis-platin.

Synthesis, spectroscopic studies, antimicrobial activities and antitumor of a new monodentate V-shaped Schiff base and its transition metal complexes.

PubMed

Ramadan, Ramadan M; Abu Al-Nasr, Ahmad K; Noureldeen, Amani F H

2014-11-11

Reaction of 4-aminoacetophenone and 4-bromobenzaldehyde in ethanol resulted in the formation of the monodentate V-shaped Schiff base (E)-1-(4-((4-bromo-benzylidene)amino)phenyl)ethanone (L). Interaction of L with different di- and trivalent metal ions revealed disubstituted derivatives. The ligand and its complexes were characterized by elemental analysis, mass, IR and NMR spectrometry. Biological activities of the ligand and complexes against the Escherchia coli and Staphylococcus aureus bacterias, and the two fungus Aspergillus flavus and Candida albicans were screened. The cytotoxicity of the compounds were checked as antitumor agents on liver carcinoma cell line (HepG2). They exhibited in vitro broad range of antitumor activities towards the cell line; the [ZnL2(H2O)2](NO3)2 complex was stronger antitumor towards HepG2 cell line as well as two breast cancer cell lines (MCF7 and T47D) relative to cis-platin. Copyright © 2014 Elsevier B.V. All rights reserved.

Inflammation--a lifelong companion. Attempt at a non-analytical holistic view.

PubMed

Ferencík, M; Stvrtinová, V; Hulín, I; Novák, M

2007-01-01

Inflammation is a key component of the immune system. It has important functions in both defense and pathophysiological events maintaining the dynamic homeostasis of a host organism including its tissues, organs and individual cells. On the cellular level it is controlled by more than 400 currently known genes. Their polymorphisms and environmental conditions give rise to different genotypes in human population. Pro-inflammatory genotype, which dominates in the present population, may be advantageous in childhood but not in elderly people because it is characterized by an increased vulnerability to, and intensity of, inflammatory reactions. These reactions may be the possible reasons of chronic inflammatory diseases, especially in old age. Better understanding of complex molecular and cellular inflammatory mechanisms is indispensable for detailed knowledge of pathogenesis of many diseases, their prevention and directed drug therapy. Here we summarize the basic current knowledge on these mechanisms.

LINE-1 silencing by retinoblastoma proteins is effected through the nucleosomal and remodeling deacetylase multiprotein complex.

PubMed

Montoya-Durango, Diego E; Ramos, Kenneth A; Bojang, Pasano; Ruiz, Lorell; Ramos, Irma N; Ramos, Kenneth S

2016-01-25

Long Interspersed Nuclear Element-1 (L1) is an oncogenic mammalian retroelement silenced early in development via tightly controlled epigenetic mechanisms. We have previously shown that the regulatory region of human and murine L1s interact with retinoblastoma (RB) proteins to effect retroelement silencing. The present studies were conducted to identify the corepressor complex responsible for RB-mediated silencing of L1. Chromatin immunoprecipitation and silencing RNA technology were used to identify the repressor complex that silences L1 in human and murine cells. Components of the Nucleosomal and Remodeling Deacetylase (NuRD) multiprotein complex specifically enriched the L1 5'-untranslated DNA sequence in human and murine cells. Genetic ablation of RB proteins in murine cells destabilized interactions within the NuRD macromolecular complex and mediated nuclear rearrangement of Mi2-β, an ATP-dependent helicase subunit with nucleosome remodeling activity. Depletion of Mi2-β, RbAP46 and HDAC2 reduced the repressor activity of the NuRD complex and reactivated a synthetic L1 reporter in human cells. Epigenetic reactivation of L1 in RB-null cells by DNA damage was markedly enhanced compared to wild type cells. RB proteins stabilize interactions of the NuRD corepressor complex within the L1 promoter to effect L1 silencing. L1 retroelements may serve as a scaffold on which RB builds heterochromatic regions that regulate chromatin function.

Theoretical thermal conductivity equation for uniform density wood cells

Treesearch

John F. Hunt; Hongmei Gu; Patricia Lebow

2008-01-01

The anisotropy of wood creates a complex problem requiring that analyses be based on fundamental material properties and characteristics of the wood structure to solve heat transfer problems. A two-dimensional finite element model that evaluates the effective thermal conductivity of a wood cell over the full range of moisture contents and porosities was previously...

Finite element analysis of the stiffness of fabric reinforced composites

NASA Technical Reports Server (NTRS)

Foye, R. L.

1992-01-01

The objective of this work is the prediction of all three dimensional elastic moduli of textile fabric reinforced composites. The analysis is general enough for use with complex reinforcing geometries and capable of subsequent improvements. It places no restrictions on fabric microgeometry except that the unit cell be determinate and rectangular. The unit cell is divided into rectangular subcells in which the reinforcing geometries are easier to define and analyze. The analysis, based on inhomogeneous finite elements, is applied to a variety of weave, braid, and knit reinforced composites. Some of these predictions are correlated to test data.

Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL) Reveals the Sequential Differentiation of Sieve Element-Like Cells.

PubMed

Kondo, Yuki; Nurani, Alif Meem; Saito, Chieko; Ichihashi, Yasunori; Saito, Masato; Yamazaki, Kyoko; Mitsuda, Nobutaka; Ohme-Takagi, Masaru; Fukuda, Hiroo

2016-06-01

Cell differentiation is a complex process involving multiple steps, from initial cell fate specification to final differentiation. Procambial/cambial cells, which act as vascular stem cells, differentiate into both xylem and phloem cells during vascular development. Recent studies have identified regulatory cascades for xylem differentiation. However, the molecular mechanism underlying phloem differentiation is largely unexplored due to technical challenges. Here, we established an ectopic induction system for phloem differentiation named Vascular Cell Induction Culture System Using Arabidopsis Leaves (VISUAL). Our results verified similarities between VISUAL-induced Arabidopsis thaliana phloem cells and in vivo sieve elements. We performed network analysis using transcriptome data with VISUAL to dissect the processes underlying phloem differentiation, eventually identifying a factor involved in the regulation of the master transcription factor gene APL Thus, our culture system opens up new avenues not only for genetic studies of phloem differentiation, but also for future investigations of multidirectional differentiation from vascular stem cells. © 2016 American Society of Plant Biologists. All rights reserved.

A novel VLSI processor architecture for supercomputing arrays

NASA Technical Reports Server (NTRS)

Venkateswaran, N.; Pattabiraman, S.; Devanathan, R.; Ahmed, Ashaf; Venkataraman, S.; Ganesh, N.

1993-01-01

Design of the processor element for general purpose massively parallel supercomputing arrays is highly complex and cost ineffective. To overcome this, the architecture and organization of the functional units of the processor element should be such as to suit the diverse computational structures and simplify mapping of complex communication structures of different classes of algorithms. This demands that the computation and communication structures of different class of algorithms be unified. While unifying the different communication structures is a difficult process, analysis of a wide class of algorithms reveals that their computation structures can be expressed in terms of basic IP,IP,OP,CM,R,SM, and MAA operations. The execution of these operations is unified on the PAcube macro-cell array. Based on this PAcube macro-cell array, we present a novel processor element called the GIPOP processor, which has dedicated functional units to perform the above operations. The architecture and organization of these functional units are such to satisfy the two important criteria mentioned above. The structure of the macro-cell and the unification process has led to a very regular and simpler design of the GIPOP processor. The production cost of the GIPOP processor is drastically reduced as it is designed on high performance mask programmable PAcube arrays.

New 15-membered tetraaza (N4) macrocyclic ligand and its transition metal complexes: Spectral, magnetic, thermal and anticancer activity

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.; EL-Gammal, Ohyla A.

2015-03-01

Novel tetraamidemacrocyclic 15-membered ligand [L] i.e. naphthyl-dibenzo[1,5,9,12]tetraazacyclopentadecine-6,10,11,15-tetraoneand its transition metal complexes with Fe(II), Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been synthesized and characterized by elemental analysis, spectral, thermal as well as magnetic and molar conductivity measurements. On the basis of analytical, spectral (IR, MS, UV-Vis, 1H NMR and EPR) and thermal studies distorted octahedral or square planar geometry has been proposed for the complexes. The antitumor activity of the synthesized ligand and some complexes against human breast cancer cell lines (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The complexes (IC50 = 2.27-2.7, 8.33-31.1 μg/mL, respectively) showed potent antitumor activity, towards the former cell lines comparable with their ligand (IC50 = 13, 26 μg/mL, respectively). The results show that the activity of the ligand towards breast cancer cell line becomes more pronounced and significant when coordinated to the metal ion.

[Reflections of child hospitalization in the life of the familiar attender].

PubMed

Santos, Leidiene Ferreira; Oliveira, Lizete Malagoni de Almeida Cavalcante; Barbosa, Maria Alves; Siqueira, Karina Machado; Peixoto, Myrian Karla Ayres Veronez

2013-01-01

This is an assistance convergent research, which aimed to investigate the effects of child's hospitalization in the companion family life. It was performed in a hospital located in Goiania-GO, Brazil, where parents of hospitalized children participated in a support group. Data collection occurred from 2010 February to July, through the recording and transcription of group sessions; to analyze the facts and phenomena experienced in the group, it was used the thematic analysis. The results provide subsidies for health professionals that allow them to understand how complex is the experience of "having" and "live" with a family child in situation of illness and hospitalization. We conclude that this experience affects family relationships, mental and physical health, and the maintenance of the social networking of the companion.

Selfish DNA: a pharmaceutical perspective.

PubMed

Winckler, T

2013-07-01

Almost 25 years ago, Theo Dingermann published the discovery of a new mobile genetic element in the unicellular microbe Dictyostelium discoideum in the journal Science. An interesting property of this new molecular parasite, the Dictyostelium Repetitive Element (DRE), was that all integrations were found approximately 50 base pairs (bp) upstream of transfer RNA (tRNA) genes in the D. discoideum genome, thus implying an active targeting mechanism to avoid the disruption of host cell genes by the retrotransposition process. Since then, the facultative multicellular "social amoeba" D. discoideum has become a popular model for analyzing complex cellular functions such as cell movement, chemotaxis, phagocytosis, and cell differentiation, important areas of biomedical research that are often hard to investigate in cells from "higher organisms" including humans. Therefore, progress in the development of methods to study Dictyostelium biology has also provoked research on transposable elements in this organism. Early work on the DRE element suggested that studying its molecular mechanism of site-specific integration might promote human gene therapy technology through the design of integrating gene transfer vectors with low intrinsic genotoxic potential. In this review article, I will briefly review the original research performed on the DRE transposable element in the Dingermann lab and report on how the emergence of genomics technologies and the development of tools to analyze de novo retrotransposition events in D. discoideum cells will expand our knowledge of DRE biology in the future.

45 CFR 2551.41 - Who is eligible to be a Senior Companion?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Who is eligible to be a Senior Companion? 2551.41... AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Eligibility, Status, and Cost Reimbursements § 2551.41 Who is eligible to be a Senior Companion? (a) To be a Senior Companion, an individual...

45 CFR 2551.42 - What types of criminal convictions or other adjudications disqualify an individual from serving...

Code of Federal Regulations, 2010 CFR

2010-10-01

... adjudications disqualify an individual from serving as a Senior Companion or as a Senior Companion grant-funded...) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Eligibility, Status... an individual from serving as a Senior Companion or as a Senior Companion grant-funded employee? Any...

AP1 binding site is another target of FGF2 regulation of bone sialoprotein gene transcription.

PubMed

Takai, Hideki; Araki, Shouta; Mezawa, Masaru; Kim, Dong-Soon; Li, Xinyue; Yang, Li; Li, Zhengyang; Wang, Zhitao; Nakayama, Youhei; Ogata, Yorimasa

2008-02-29

Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. We previously reported that fibroblast growth factor 2 (FGF2) regulates BSP gene transcription via FGF2 response element (FRE) in the proximal promoter of rat BSP gene. We here report that activator protein 1 (AP1) binding site overlapping with glucocorticoid response element (GRE) AP1/GRE in the rat BSP gene promoter is another target of FGF2. Using the osteoblastic cell line ROS17/2.8, we determined that BSP mRNA levels increased by 10 ng/ml FGF2 at 6 and 12 h. Runx2 protein levels increased by FGF2 (10 ng/ml) at 3 h. Treatment of ROS17/2.8 cells with FGF2 (10 ng/ml, 12 h) increased luciferase activities of constructs including -116 to +60 and -938 to +60 of the rat BSP gene promoter. Effects of FGF2 abrogated in constructs included 2 bp mutations in the FRE and AP1/GRE elements. Luciferase activities induced by FGF2 were blocked by tyrosine kinase inhibitor herbimycin A, src-tyrosine kinase inhibitor PP1 and MAP kinase kinase inhibitor U0126. Gel shift analyses showed that FGF2 increased binding of FRE and AP1/GRE elements. Notably, the AP1/GRE-protein complexes were supershifted by Smad1 and c-Fos antibodies, c-Jun and Dlx5 antibodies disrupted the complexes formation, on the other hand AP1/GRE-protein complexes did not change by Runx2 antibody. These studies demonstrate that FGF2 stimulates BSP gene transcription by targeting the FRE and AP1/GRE elements in the rat BSP gene promoter.

Excitons in intact cells of photosynthetic bacteria.

PubMed

Freiberg, Arvi; Pajusalu, Mihkel; Rätsep, Margus

2013-09-26

Live cells and regular crystals seem fundamentally incompatible. Still, effects characteristic to ideal crystals, such as coherent sharing of excitation, have been recently used in many studies to explain the behavior of several photosynthetic complexes, especially the inner workings of the light-harvesting apparatus of the oldest known photosynthetic organisms, the purple bacteria. To this date, there has been no concrete evidence that the same effects are instrumental in real living cells, leaving a possibility that this is an artifact of unnatural study conditions, not a real effect relevant to the biological operation of bacteria. Hereby, we demonstrate survival of collective coherent excitations (excitons) in intact cells of photosynthetic purple bacteria. This is done by using excitation anisotropy spectroscopy for tracking the temperature-dependent evolution of exciton bands in light-harvesting systems of increasing structural complexity. The temperature was gradually raised from 4.5 K to ambient temperature, and the complexity of the systems ranged from detergent-isolated complexes to complete bacterial cells. The results provide conclusive evidence that excitons are indeed one of the key elements contributing to the energetic and dynamic properties of photosynthetic organisms.

Low-Metallicity Lead Stars: Comparison between Theory and Observations

NASA Astrophysics Data System (ADS)

Bisterzo, S.; Gallino, R.; Straniero, O.; Aoki, W.; Ryan, S.; Beers, T. C.

2006-07-01

We compare AGB theoretical models with spectroscopic abundances of a sample of very metal-poor, C-rich, s-rich and lead-rich stars observed at high-resolution spectroscopy. Fits are obtained for AGB models with different 13C-pocket efficiencies and initial masses. The two intrinsic indicators, [hs/ls] and [Pb/hs] versus [Fe/H], are analyzed. An extended analysis of all the observed elements is made, outlining apparent discrepancies for a few elements. The analysis of C and N abundances strengthen the need of a strong cool bottom process occurring during the AGB. A significant number of these stars are both s-enriched and r-enriched. For them, the envelope abundances are predicted by mass transfer from the more massive AGB companion in a binary system from a parental cloud already enriched in r-elements.

Sex Differences in Stress and Group Housing Effects on the Number of Newly Proliferated Cells and Neuroblasts in Middle-Aged Dentate Gyrus.

PubMed

Tzeng, Wen-Yu; Wu, Hsin-Hua; Wang, Ching-Yi; Chen, Jin-Chung; Yu, Lung; Cherng, Chianfang G

2016-01-01

Sex differences in stress and coping responses have been frequently documented in aged people, while whether such differences in aged people may appear at the middle age are unknown. This study was undertaken to study the impact of acute stress and social interaction on early neurogenesis in the dentate gyrus (DG) and hippocampus-related memory in two sexes of middle-aged mice. The number of newly proliferated cells, neuroblasts in DG, the object recognition and location memory in 9-month-old male and female C57BL/6N mice were assessed under baseline conditions as well as following an acute stressor regimen and group housing. Three conspecific companions, serving as "the housing group," were used to model the social interaction throughout the stressor regimen. Males had lower numbers of newly proliferated cells and neuroblasts under baseline conditions as compared to females. The stressor regimen caused rapid decreases in the number of newly proliferated cells and neuroblasts in female DG but no obvious changes were observed in male DG. Group housing, regardless of companions' age, prevented the stress-induced decreases in the number of newly proliferated cells and neuroblasts in female DG. In contrast, the presence of young or age-matched companions potentiated the stress effect in males by decreasing the number of newly proliferated cells and neuroblasts. Finally, neither the stressor regimen nor group housing affected mouse performances in the object recognition and location memory in either sex. These findings, taken together, provide evidence to support a notion that middle-aged females appear to demonstrate more stress susceptibility on early neurogenesis in DG as compared to middle-aged males, although the hippocampus-related memory performances are comparable and not affected by stress in these males and females. Experiencing stress, middle-aged females are more prone to benefit from social interaction as compared to middle-aged males in this regard. We suggest, accordingly, that involving social interaction may afford a therapeutic advance in preventing stress-produced decreases in early neurogenesis in middle-aged females' DG.

(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

DOE Office of Scientific and Technical Information (OSTI.GOV)

Markham, Jack; Liang, Jun; Levina, Aviva

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less

(Pentamethylcyclopentadienato)rhodium complexes for delivery of the curcumin anticancer drug [Rhodium pentamethylcyclopentadienato complexes for delivery of the curcumin anti-cancer drug

DOE PAGES

Markham, Jack; Liang, Jun; Levina, Aviva; ...

2017-01-23

[RhIII(*Cp)Cl(X,Y)] n+ complexes {X, Y = Cl, PTA, n = 0 (2); X, Y = en, n = 1 (3, Cl– salt; 4, PF 6– salt); X, Y = acac, n = 0 (5); X, Y = cur, n = 0 (6), where *Cp = pentamethylcyclopentadienato, curH = curcumin; PTA = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane; en = 1,2-ethanediamine; acac = acetylacetonato = 2,4-pentanedionato(1–)} were synthesized from [Rh(*Cp)(µ-Cl)Cl] 2 (1). While 2–5 were inactive against human epithelial A549 lung-cancer cells in assays of cytotoxicity, and antimetastatic and proapoptotic behaviors, 6 had a cytotoxic activity similar to that of curH over 72 h, but atmore » 24 h in real-time cell migration assays, it was less active, showing slow release of curH. All complexes underwent ligand-exchange reactions with biomolecules and cells within the timeframes of the assays (X-ray absorption spectroscopy). Intracellular elemental distributions (X-ray fluorescence microscopy) showed that 6 effectively delivered curH to cells, where it was released. Other elemental distributions and caspase activities were consistent with preapoptotic activities. As such, 6 is a promising delivery agent for bioactive ligands, such as curH. However, pure curcumin itself showed a previously unrecognized ability to promote migration of A549 cells at subtoxic concentrations in the presence of endothelial growth factor, which may be a concern for its widespread use as a nutritional supplement and as a potential drug. As a result, this aspect warrants further research.« less

Antimycobacterial action of a new glycolipid-peptide complex obtained from extracellular metabolites of Raoultella ornithinolytica.

PubMed

Fiołka, Marta J; Grzywnowicz, Krzysztof; Mendyk, Ewaryst; Zagaja, Mirosław; Szewczyk, Rafał; Rawski, Michał; Keller, Radosław; Rzymowska, Jolanta; Wydrych, Jerzy

2015-12-01

In this paper, an antimycobacterial component of extracellular metabolites of a gut bacterium Raoultella ornithinolytica from D. veneta earthworms was isolated and its antimycobacterial action was tested using Mycobacterium smegmatis. After incubation with the complex obtained, formation of pores and furrows in cell walls was observed using microscopic techniques. The cells lost their shape, stuck together and formed clusters. Surface-enhanced Raman spectroscopy analysis showed that, after incubation, the complex was attached to the cell walls of the Mycobacterium. Analyses of the component performed with Fourier transform infrared spectroscopy demonstrated high similarity to a bacteriocin nisin, but energy dispersive X-ray spectroscopy analysis revealed differences in the elemental composition of this antimicrobial peptide. The component with antimycobacterial activity was identified using mass spectrometry techniques as a glycolipid-peptide complex. As it exhibits no cytotoxicity on normal human fibroblasts, the glycolipid-peptide complex appears to be a promising compound for investigations of its activity against pathogenic mycobacteria. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Synthesis and characterization of a metal complex containing naringin and Cu, and its antioxidant, antimicrobial, antiinflammatory and tumor cell cytotoxicity.

PubMed

Pereira, Regina M S; Andrades, Norma E D; Paulino, Niraldo; Sawaya, Alexandra C H F; Eberlin, Marcos N; Marcucci, Maria C; Favero, Giovani Marino; Novak, Estela Maria; Bydlowski, Sérgio Paulo

2007-07-09

The antioxidant activity of flavonoids is believed to increase when they are coordinated with transition metal ions. However, the literature on this subject is contradictory and the outcome seems to largely depend on the experimental conditions. In order to understand the contribution of the metal coordination and the type of interaction between a flavonoid and the metal ion, in this study a new metal complex of Cu (II) with naringin was synthesized and characterized by FT-IR, UV-VIS, mass spectrometry (ESI-MS/MS), elemental analysis and 1H-NMR. The results of these analyses indicate that the complex has a Cu (II) ion coordinated via positions 4 and 5 of the flavonoid. The antioxidant, anti-inflammatory and antimicrobial activities of this complex were studied and compared with the activity of free naringin. The Naringin-Cu (II) complex 1 showed higher antioxidant, anti-inflammatory and tumor cell cytotoxicity activities than free naringin without reducing cell viability.

Temperature and Oxygen Effects on 14C-Photosynthate Unloading and Accumulation in Developing Soybean Seeds

PubMed Central

Thorne, John H.

1982-01-01

The environmental sensitivity of the processes associated with the import of photosynthate by developing soybean seeds was investigated within intact fruit and with excised, immature embryos. Intact pods of field-grown (Glycine max [L.] Merr.) Amsoy 71 soybeans were subjected to localized regimes of 0, 21, or 100% O2 and 15, 25, or 35°C during pulsechase translocation experiments and, 2.5 hours later, the uptake and distribution of 14C-photosynthate among dissected fruit tissues determined. In other experiments, excised embryos were incubated in [14C]sucrose solutions under various experimental conditions to separate the effects of these treatments on accumulation by the embryos from those which may operate on phloem unloading in the maternal seedcoat. Import of 14C-photosynthate by intact soybean fruit was both temperature- and O2-dependent. This dependency was shown to occur only within the seeds; import by the pod walls was essentially insensitive to fruit temperature or O2 treatments. The embryos of anaerobic fruit were completely unlabeled, regardless of fruit temperature. But under anaerobic in vitro incubation conditions, uptake of [14C]sucrose in excised embryos was only 30% less than that in aerobic in vitro conditions. The data suggest that, within intact fruit, anoxia prevented sucrose efflux from the seed coat phloem and any subsequent uptake by the embryo. The demonstrated energy dependence of phloem unloading may reflect requirements for membrane integrity or energy metabolism in the companion cell-sieve element complex, consistent with a facilitated unloading process. Collectively, these data characterize the environmental sensitivity of photosynthate import in developing soybean fruit. They imply that environmental regulation of import may occur at both the embryo level and at the phloem terminals within the seed coat. PMID:16662182

The HILDA Complex Coordinates a Conditional Switch in the 3′-Untranslated Region of the VEGFA mRNA

PubMed Central

Yao, Peng; Potdar, Alka A.; Ray, Partho Sarothi; Eswarappa, Sandeepa M.; Flagg, Andrew C.; Willard, Belinda; Fox, Paul L.

2013-01-01

Cell regulatory circuits integrate diverse, and sometimes conflicting, environmental cues to generate appropriate, condition-dependent responses. Here, we elucidate the components and mechanisms driving a protein-directed RNA switch in the 3′UTR of vascular endothelial growth factor (VEGF)-A. We describe a novel HILDA (hypoxia-inducible hnRNP L–DRBP76–hnRNP A2/B1) complex that coordinates a three-element RNA switch, enabling VEGFA mRNA translation during combined hypoxia and inflammation. In addition to binding the CA-rich element (CARE), heterogeneous nuclear ribonucleoprotein (hnRNP) L regulates switch assembly and function. hnRNP L undergoes two previously unrecognized, condition-dependent posttranslational modifications: IFN-γ induces prolyl hydroxylation and von Hippel-Lindau (VHL)-mediated proteasomal degradation, whereas hypoxia stimulates hnRNP L phosphorylation at Tyr359, inducing binding to hnRNP A2/B1, which stabilizes the protein. Also, phospho-hnRNP L recruits DRBP76 (double-stranded RNA binding protein 76) to the 3′UTR, where it binds an adjacent AU-rich stem-loop (AUSL) element, “flipping” the RNA switch by disrupting the GAIT (interferon-gamma-activated inhibitor of translation) element, preventing GAIT complex binding, and driving robust VEGFA mRNA translation. The signal-dependent, HILDA complex coordinates the function of a trio of neighboring RNA elements, thereby regulating translation of VEGFA and potentially other mRNA targets. The VEGFA RNA switch might function to ensure appropriate angiogenesis and tissue oxygenation during conflicting signals from combined inflammation and hypoxia. We propose the VEGFA RNA switch as an archetype for signal-activated, protein-directed, multi-element RNA switches that regulate posttranscriptional gene expression in complex environments. PMID:23976881

Histone Deacetylase-1 Is Enriched at the Platelet-derived Growth Factor-D Promoter in Response to Interleukin-1β and Forms a Cytokine-inducible Gene-silencing Complex with NF-κB p65 and Interferon Regulatory Factor-1*

PubMed Central

Liu, Mary Y.; Khachigian, Levon M.

2009-01-01

Understanding the mechanisms governing cytokine control of growth factor expression in smooth muscle cells would provide invaluable insight into the molecular regulation of vascular phenotypes and create future opportunities for therapeutic intervention. Here, we report that the proinflammatory cytokine interleukin (IL)-1β suppresses platelet-derived growth factor (PDGF)-D promoter activity and mRNA and protein expression in smooth muscle cells. NF-κB p65, induced by IL-1β, interacts with a novel element in the PDGF-D promoter and inhibits PDGF-D transcription. Interferon regulatory factor-1 (IRF-1) is also induced by IL-1β and binds to a different element upstream in the promoter. Immunoprecipitation and chromatin immunoprecipitation experiments showed that IL-1β stimulates p65 interaction with IRF-1 and the accumulation of both factors at the PDGF-D promoter. Mutation of the IRF-1 and p65 DNA-binding elements relieved the promoter from IL-1β-mediated repression. PDGF-D repression by IL-1β involves histone deacetylation and interaction of HDAC-1 with IRF-1 and p65. HDAC-1 small interfering RNA ablates complex formation with IRF-1 and p65 and abrogates IRF-1 and p65 occupancy of the PDGF-D promoter. Thus, HDAC-1 is enriched at the PDGF-D promoter in cells exposed to IL-1β and forms a cytokine-inducible gene-silencing complex with p65 and IRF-1. PMID:19843519

Intracellular distribution and stability of a luminescent rhenium(I) tricarbonyl tetrazolato complex using epifluorescence microscopy in conjunction with X-ray fluorescence imaging

DOE PAGES

Wedding, Jason L.; Harris, Hugh H.; Bader, Christie A.; ...

2016-11-23

Optical fluorescence microscopy was used in conjunction with X-ray fluorescence microscopy to monitor the stability and intracellular distribution of the luminescent rhenium(I) complex fac-[Re(CO) 3(phen)L], where phen = 1,10-phenathroline and L = 5-(4-iodophenyl)tetrazolato, in 22Rv1 cells. The rhenium complex showed no signs of ancillary ligand dissociation, a conclusion based on data obtained via X-ray fluorescence imaging aligning iodine and rhenium distributions. A diffuse reticular localisation was detected for the complex, in the nuclear/perinuclear region of cells, by either optical or X-ray fluorescence techniques. Furthermore, X-ray fluorescence also showed that the Re-I complex disrupted the homeostasis of some biologically relevant elements,more » such as chlorine, potassium and zinc.« less

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules.

PubMed

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I; de Boer, Pascal; Hagen, Kees C W; Hoogenboom, Jacob P; Giepmans, Ben N G

2017-04-07

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale 'color-EM' as a promising tool to unravel molecular (de)regulation in biomedicine.

Multi-color electron microscopy by element-guided identification of cells, organelles and molecules

PubMed Central

Scotuzzi, Marijke; Kuipers, Jeroen; Wensveen, Dasha I.; de Boer, Pascal; Hagen, Kees (C.) W.; Hoogenboom, Jacob P.; Giepmans, Ben N. G.

2017-01-01

Cellular complexity is unraveled at nanometer resolution using electron microscopy (EM), but interpretation of macromolecular functionality is hampered by the difficulty in interpreting grey-scale images and the unidentified molecular content. We perform large-scale EM on mammalian tissue complemented with energy-dispersive X-ray analysis (EDX) to allow EM-data analysis based on elemental composition. Endogenous elements, labels (gold and cadmium-based nanoparticles) as well as stains are analyzed at ultrastructural resolution. This provides a wide palette of colors to paint the traditional grey-scale EM images for composition-based interpretation. Our proof-of-principle application of EM-EDX reveals that endocrine and exocrine vesicles exist in single cells in Islets of Langerhans. This highlights how elemental mapping reveals unbiased biomedical relevant information. Broad application of EM-EDX will further allow experimental analysis on large-scale tissue using endogenous elements, multiple stains, and multiple markers and thus brings nanometer-scale ‘color-EM’ as a promising tool to unravel molecular (de)regulation in biomedicine. PMID:28387351

Family companions' involvement during pre-surgical consent visits for major cancer surgery and its relationship to visit communication and satisfaction.

PubMed

Isenberg, Sarina R; Aslakson, Rebecca A; Dionne-Odom, James N; Clegg Smith, Katherine; Singh, Sarabdeep; Larson, Susan; Bridges, John F P; Smith, Thomas J; Wolff, Jennifer L; Roter, Debra L

2018-06-01

To examine the association between family companion presence during pre-surgical visits to discuss major cancer surgery and patient-provider communication and satisfaction. Secondary analysis of 61 pre-surgical visit recordings with eight surgical oncologists at an academic tertiary care hospital using the Roter Interaction Analysis System (RIAS). Surgeons, patients, and companions completed post-visit satisfaction questionnaires. Poisson and logistic regression models assessed differences in communication and satisfaction when companions were present vs. absent. There were 46 visits (75%) in which companions were present, and 15 (25%) in which companions were absent. Companion communication was largely emotional and facilitative, as measured by RIAS. Companion presence was associated with more surgeon talk (IRR 1.29, p = 0.006), and medical information-giving (IRR 1.41, p = 0.001). Companion presence was associated with less disclosure of lifestyle/psychosocial topics by patients (IRR 0.55, p = 0.037). In adjusted analyses, companions' presence was associated with lower levels of patient-centeredness (IRR 0.77, p 0.004). There were no differences in patient or surgeon satisfaction based on companion presence. Companions' presence during pre-surgical visits was associated with patient-surgeon communication but was not associated with patient or surgeon satisfaction. Future work is needed to develop interventions to enhance patient-companion-provider interactions in this setting. Copyright © 2018 Elsevier B.V. All rights reserved.

The third person in the room: frequency, role, and influence of companions during primary care medical encounters.

PubMed

Schilling, Lisa M; Scatena, Lisa; Steiner, John F; Albertson, Gail A; Lin, C T; Cyran, Lisa; Ware, Lindsay; Anderson, Robert J

2002-08-01

We wanted to characterize patient accompaniment to medical encounters and to explore the rationale and influence of the companion on the primary care medical encounter. This was a descriptive study. Academic general internal medicine physicians, patients, and patient companions participated. We measured the frequency of waiting and examination room companions, the reasons for accompaniment, the influence on the encounter, and the overall helpfulness of the companion as assessed by patients and companions. We also determined the physicianamprsquos assessment of the companionamprsquos influence, helpfulness, and behavior during the encounter. Companions were in the examination room for 16% of visits; 93% were family members. The rationales for waiting and examination room companions were to help with transportation, provide emotional support, and provide company. Examination room companions helped communicate concerns to the physician, remember the physicianamprsquos advice, make decisions, and communicate their own concerns to the physician. Patients believed that examination room companions influenced 75% of medical encounters, mainly by improving communication between physician and patient. Physicians agreed that examination room companions favorably influenced physician and patient understanding (60% and 46% of encounters, respectively). Patients indicated that waiting and examination room companions were very helpful for 71% and 83% of visits, respectively. Companions frequently accompany patients to their primary care medical encounters. They are often family members, and they assume important roles in enhancing patient and physician understanding.

PML–RARA-RXR Oligomers Mediate Retinoid and Rexinoid/cAMP Cross-Talk in Acute Promyelocytic Leukemia Cell Differentiation

PubMed Central

Kamashev, Dmitrii; Vitoux, Dominique; de Thé, Hugues

2004-01-01

PML–RARA was proposed to initiate acute promyelocytic leukemia (APL) through PML–RARA homodimer–triggered repression. Here, we examined the nature of the PML–RARA protein complex and of its DNA targets in APL cells. Using a selection/amplification approach, we demonstrate that PML–RARA targets consist of two AGGTCA elements in an astonishing variety of orientations and spacings, pointing to highly relaxed structural constrains for DNA binding and identifying a major gain of function of this oncogene. PML–RARA-specific response elements were identified, which all conveyed a major transcriptional response to RA only in APL cells. In these cells, we demonstrate that PML–RARA oligomers are complexed to RXR. Directly probing PML–RARA function in APL cells, we found that the differentiation enhancer cyclic AMP (cAMP) boosted transcriptional activation by RA. cAMP also reversed the normal silencing (subordination) of the transactivating function of RXR when bound to RARA or PML–RARA, demonstrating that the alternate rexinoid/cAMP-triggered APL differentiation pathway also activates PML–RARA targets. Finally, cAMP restored both RA-triggered differentiation and PML–RARA transcriptional activation in mutant RA-resistant APL cells. Collectively, our findings directly demonstrate that APL cell differentiation parallels transcriptional activation through PML–RARA-RXR oligomers and that those are functionally targeted by cAMP, identifying this agent as another oncogene-targeted therapy. PMID:15096541

The orphan receptor hepatic nuclear factor 4 functions as a transcriptional activator for tissue-specific and hypoxia-specific erythropoietin gene expression and is antagonized by EAR3/COUP-TF1.

PubMed

Galson, D L; Tsuchiya, T; Tendler, D S; Huang, L E; Ren, Y; Ogura, T; Bunn, H F

1995-04-01

The erythropoietin (Epo) gene is regulated by hypoxia-inducible cis-acting elements in the promoter and in a 3' enhancer, both of which contain consensus hexanucleotide hormone receptor response elements which are important for function. A group of 11 orphan nuclear receptors, transcribed and translated in vitro, were screened by the electrophoretic mobility shift assay. Of these, hepatic nuclear factor 4 (HNF-4), TR2-11, ROR alpha 1, and EAR3/COUP-TF1 bound specifically to the response elements in the Epo promoter and enhancer and, except for ROR alpha 1, formed DNA-protein complexes that had mobilities similar to those observed in nuclear extracts of the Epo-producing cell line Hep3B. Moreover, both anti-HNF-4 and anti-COUP antibodies were able to supershift complexes in Hep3B nuclear extracts. Like Epo, HNF-4 is expressed in kidney, liver, and Hep3B cells but not in HeLa cells. Transfection of a plasmid expressing HNF-4 into HeLa cells enabled an eightfold increase in the hypoxic induction of a luciferase reporter construct which contains the minimal Epo enhancer and Epo promoter, provided that the nuclear hormone receptor consensus DNA elements in both the promoter and the enhancer were intact. The augmentation by HNF-4 in HeLa cells could be abrogated by cotransfection with HNF-4 delta C, which retains the DNA binding domain of HNF-4 but lacks the C-terminal activation domain. Moreover, the hypoxia-induced expression of the endogenous Epo gene was significantly inhibited in Hep3B cells stably transfected with HNF-4 delta C. On the other hand, cotransfection of EAR3/COUP-TF1 and the Epo reporter either with HNF-4 into HeLa cells or alone into Hep3B cells suppressed the hypoxia induction of the Epo reporter. These electrophoretic mobility shift assay and functional experiments indicate that HNF-4 plays a critical positive role in the tissue-specific and hypoxia-inducible expression of the Epo gene, whereas the COUP family has a negative modulatory role.

Pyrrolidine dithiocarbamate-zinc(II) and -copper(II) complexes induce apoptosis in tumor cells by inhibiting the proteasomal activity☆

PubMed Central

Milacic, Vesna; Chen, Di; Giovagnini, Lorena; Diez, Alejandro; Fregona, Dolores; Dou, Q. Ping

2013-01-01

Zinc and copper are trace elements essential for proper folding, stabilization and catalytic activity of many metalloenzymes in living organisms. However, disturbed zinc and copper homeostasis is reported in many types of cancer. We have previously demonstrated that copper complexes induced proteasome inhibition and apoptosis in cultured human cancer cells. In the current study we hypothesized that zinc complexes could also inhibit the proteasomal chymotrypsin-like activity responsible for subsequent apoptosis induction. We first showed that zinc(II) chloride was able to inhibit the chymotrypsin-like activity of a purified 20S proteasome with an IC50 value of 13.8 μM, which was less potent than copper(II) chloride (IC50 5.3 μM). We then compared the potencies of a pyrrolidine dithiocarbamate (PyDT)-zinc(II) complex and a PyDT-copper(II) complex to inhibit cellular proteasomal activity, suppress proliferation and induce apoptosis in various human breast and prostate cancer cell lines. Consistently, zinc complex was less potent than copper complex in inhibiting the proteasome and inducing apoptosis. Additionally, zinc and copper complexes appear to use somewhat different mechanisms to kill tumor cells. Zinc complexes were able to activate calpain-, but not caspase-3-dependent pathway, while copper complexes were able to induce activation of both proteases. Furthermore, the potencies of these PyDT-metal complexes depend on the nature of metals and also on the ratio of PyDT to the metal ion within the complex, which probably affects their stability and availability for interacting with and inhibiting the proteasome in tumor cells. PMID:18501397

AP1 Keeps Chromatin Poised for Action | Center for Cancer Research

Cancer.gov

The human genome harbors gene-encoding DNA, the blueprint for building proteins that regulate cellular function. Embedded across the genome, in non-coding regions, are DNA elements to which regulatory factors bind. The interaction of regulatory factors with DNA at these sites modifies gene expression to modulate cell activity. In cells, DNA exists in a complex with proteins

Clinical trial tests drug for tumors associated with Krebs-cycle dysfunction | Center for Cancer Research

Cancer.gov

The Krebs cycle is part of the complex process where cells turn food into energy. One of the elements of the Krebs cycle is succinate dehydrogenase (SDH). Loss of SDH activity in cells has been linked to tumor formation. This new trial is studying guadecitabine for tumors associated with Krebs cycle dysfunction. Learn more...

The critical binary star separation for a planetary system origin of white dwarf pollution

NASA Astrophysics Data System (ADS)

Veras, Dimitri; Xu, Siyi; Rebassa-Mansergas, Alberto

2018-01-01

The atmospheres of between one quarter and one half of observed single white dwarfs in the Milky Way contain heavy element pollution from planetary debris. The pollution observed in white dwarfs in binary star systems is, however, less clear, because companion star winds can generate a stream of matter which is accreted by the white dwarf. Here, we (i) discuss the necessity or lack thereof of a major planet in order to pollute a white dwarf with orbiting minor planets in both single and binary systems, and (ii) determine the critical binary separation beyond which the accretion source is from a planetary system. We hence obtain user-friendly functions relating this distance to the masses and radii of both stars, the companion wind, and the accretion rate on to the white dwarf, for a wide variety of published accretion prescriptions. We find that for the majority of white dwarfs in known binaries, if pollution is detected, then that pollution should originate from planetary material.

The Crucible: Adding Complexity to the Question of Social Justice in Early Childhood Development

ERIC Educational Resources Information Center

Mevawalla, Zinnia

2013-01-01

As an ideology, the concept of social justice has long been a worthy, if slightly volatile, companion of early childhood theorists and researchers. Whilst the majority of the literature has valorised social justice, discontented questions regarding "what" the construct entails and "how" it might be tamed to work still remain.…

Feasibility studies of using the Catfish Immune System to produce monoclonal antibodies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Poston, T.M.

1987-03-01

The objective of these studies was to determine the feasibility of using a teleost cell line to produce monoclonal antibodies. Studies were undertaken to demonstrate the production of a polyclonal response of channel catfish (Icatalurus punctatus) challenged with mycotoxins coupled to a protein carrier. Companion studies were also performed to induce a permanent cell line with catfish lymphocytes. Attempts to demonstrate a polyclonal response to haptenized mycotoxins were inconclusive. Tests to induce an immortal, permanent cell line with benzene and x-ray irradiated cells were also inconclusive. 3 refs., 13 tabs.

"SPEAKING-FOR" AND "SPEAKING-AS": PSEUDO-SURROGACY IN PHYSICIANPATIENT-COMPANION MEDICAL ENCOUNTERS ABOUT ADVANCED CANCER

PubMed Central

Mazer, Benjamin L.; Cameron, Rachel A.; DeLuca, Jane M.; Mohile, Supriya G.; Epstein, Ronald M.

2014-01-01

Objective To examine using audio-recorded encounters the extent and process of companion participation when discussing treatment choices and prognosis in the context of a life-limiting cancer diagnosis. Methods Qualitative analysis of transcribed outpatient visits between 17 oncologists, 49 patients with advanced cancer, and 34 companions. Results 46 qualifying companion statements were collected from a total of 28 conversations about treatment choices or prognosis. We identified a range of companion positions, from “pseudo-surrogacy” (companion speaking as if the patient were not able to speak for himself), “hearsay”, “conflation of thoughts”, “co-experiencing”, “observation as an outsider”, and “facilitation”. Statements made by companions were infrequently directly validated by the patient. Conclusions Companions often spoke on behalf of patients during discussions of prognosis and treatment choices, even when the patient was present and capable of speaking on his or her own behalf. Practice Implications The conversational role of companions as well as whether the physician checks with the patient can determine whether a companion facilitates or inhibits patient autonomy and involvement. Physicians can reduce ambiguity and encourage patient participation by being aware of the when and how companions may speak on behalf of patients and by corroborating the companion's statement with the patient. PMID:24862913

"Speaking-for" and "speaking-as": pseudo-surrogacy in physician-patient-companion medical encounters about advanced cancer.

PubMed

Mazer, Benjamin L; Cameron, Rachel A; DeLuca, Jane M; Mohile, Supriya G; Epstein, Ronald M

2014-07-01

To examine using audio-recorded encounters the extent and process of companion participation when discussing treatment choices and prognosis in the context of a life-limiting cancer diagnosis. Qualitative analysis of transcribed outpatient visits between 17 oncologists, 49 patients with advanced cancer, and 34 companions. 46 qualifying companion statements were collected from a total of 28 conversations about treatment choices or prognosis. We identified a range of companion positions, from "pseudo-surrogacy" (companion speaking as if the patient were not able to speak for himself), "hearsay", "conflation of thoughts", "co-experiencing", "observation as an outsider", and "facilitation". Statements made by companions were infrequently directly validated by the patient. Companions often spoke on behalf of patients during discussions of prognosis and treatment choices, even when the patient was present and capable of speaking on his or her own behalf. The conversational role of companions as well as whether the physician checks with the patient can determine whether a companion facilitates or inhibits patient autonomy and involvement. Physicians can reduce ambiguity and encourage patient participation by being aware of when and how companions may speak on behalf of patients and by corroborating the companion's statement with the patient. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Synthesis, characterization and antitumor activity of Ln(III) complexes with hydrazone Schiff base derived from 2-acetylpyridine and isonicotinohydrazone

PubMed Central

Xie, Jing; Shen, Shanshan; Chen, Ruhua; Xu, Jun; Dong, Kun; Huang, Jiancui; Lu, Qin; Zhu, Wenjiao; Ma, Tieliang; Jia, Lei; Cai, Hongxin; Zhu, Taofeng

2017-01-01

In the present study, two isostructural lanthanide (Ln)(III) complexes, namely Ln(HL)2(NO3)(CH3OH)2)·CH3OH, where Ln = La in complex 1 and Ce in complex 2, and hydrogen ligand (HL) = (E)-N'-[1-(2-pyridinyl)ethylidene]isonicotinohydrazone, have been isolated and characterized by elemental analysis, infrared spectra and single-crystal X-ray diffraction analysis. The results revealed that the acylhydrazone ligand HL in each complex was deprotonated as an anionic ligand and coordinated to the central La(III) ion via enolization of oxygen and nitrogen atoms. Furthermore, the antitumor effects and potential mechanisms of the two complexes were explored in the human lung cancer cell line A549 and in the human gastric cancer cell lines BGC823 and SGC7901. In the present study, the roles the two complexes on the proliferation and apoptosis of the above tumor cell lines were determined by MTT assay and Annexin V/propidium iodide flow cytometry, respectively. Furthermore, various apoptosis-associated key genes, including caspase 3, B cell lymphoma (Bcl)-2-associated X protein (Bax) and Bcl-2, were detected by western blotting to explore the possible antitumor mechanisms of the two complexes. The results revealed that the two complexes had comparable antitumor activities in terms of inhibiting proliferation and inducing apoptosis in tumor cell lines. The changes in the protein expression levels of caspase 3, Bax and Bcl-2 further verified the apoptosis-promoting mechanisms of the two complexes in tumor cell lines. These findings have a great potential in biomedical applications of novel Ln(III) complexes. PMID:28599443

Lateralized mechanisms for encoding of object. Behavioral evidence from an animal model: the domestic chick (Gallus gallus)

PubMed Central

Rugani, Rosa; Rosa Salva, Orsola; Regolin, Lucia

2014-01-01

In our previous research we reported a leftward-asymmetry in domestic chicks required to identify a target element, on the basis of its ordinal position, in a series of identical elements. Here we re-coded behavioral data collected in previous studies from chicks tested in a task involving a different kind of numerical ability, to study lateralization in dealing with an arithmetic task. Chicks were reared with a set of identical objects representing artificial social companions. On day 4, chicks underwent a free-choice test in which two sets, each composed of a different number of identical objects (5 vs.10 or 6 vs. 9, Experiment 1), were hidden behind two opaque screens placed in front of the chick, one on the left and one on the right side. Objects disappeared, one by one, behind either screen, so that, for example, one screen occluded 5 objects and the other 10 objects. The left-right position of the larger set was counterbalanced between trials. Results show that chicks, in the attempt to rejoin the set with the higher number of social companions, performed better when this was located to the right. However, when the number of elements in the two sets was identical (2 vs. 2, in Experiment 2) and they differed only in the coloration of the objects, this bias was not observed, suggesting a predisposition to map the numerical magnitude from left to right. Future studies should be devoted to the direct investigation of this phenomenon, possibly employing an identical number of mono-chromatic imprinting stimuli in both conditions involving a numerical discrimination and conditions not involving any numerosity difference. PMID:24605106

Three diverse target preparations: 14C (12 mg/cm 2), 71Ga 24Mg (12 mg/cm 271Ga, 3 mg/cm 224Mg), and 66,67Zn (1.8-14.9 mg/cm 2)

NASA Astrophysics Data System (ADS)

Lozowski, W. R.

1989-10-01

A natural-carbon analog of fluffy, intractable 14C powder was produced. With it, a method was developed to produce a pressed disk of 14C of 12.7-mg/cm 2 thickness and 1.27-cm diameter, bound with 2.1 wt.% of adhesive. Aluminized Mylar cover foils and a fritted-disc filter were used to contain the target for ( overlinep, p') experiments. Reduction of 71Ga 2O 3 to the metal was accomplished with an efficiency of 94.3% in a small electroplating cell. Magnesium was chosen as the companion element because 50 at.% could be tolerated in the (p, n) experiment, and GaMg has a melting point of 646 K. A 1.27-cm diameter target, supported at the edge by a Mg foil, was produced in several simple steps. Directly rollable 66,67Zn foils were obtained from an electroplating cell with a Pt screen anode and a highly polished tungsten-carbide cathode. Plating times of 3 h provided metal-recovery efficiencies ranging from 94.2 to 96.5%. The as-deposited foils had many holes but were hole-free and shiny after reduction of 25% by pack rolling.

45 CFR 2551.104 - May Corporation funds be used for non-stipended Senior Companions?

Code of Federal Regulations, 2010 CFR

2010-10-01

... Senior Companions? 2551.104 Section 2551.104 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Non-Stipended Senior Companions. § 2551.104 May Corporation funds be used for non-stipended Senior Companions? Federally...

45 CFR 2551.11 - What is the Senior Companion Program?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false What is the Senior Companion Program? 2551.11... AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM General § 2551.11 What is the Senior Companion Program? The Senior Companion Program provides grants to qualified agencies and organizations for the dual...

45 CFR 2551.71 - What requirements govern the assignment of Senior Companions?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false What requirements govern the assignment of Senior...) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Placements and Assignments § 2551.71 What requirements govern the assignment of Senior Companions? (a) Senior Companion...

45 CFR 2551.103 - Must a sponsor be required to enroll non-stipended Senior Companions?

Code of Federal Regulations, 2010 CFR

2010-10-01

... Senior Companions? 2551.103 Section 2551.103 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Non-Stipended Senior Companions. § 2551.103 Must a sponsor be required to enroll non-stipended Senior Companions? Enrollment of...

Cryo-EM Structures Reveal Mechanism and Inhibition of DNA Targeting by a CRISPR-Cas Surveillance Complex.

PubMed

Guo, Tai Wei; Bartesaghi, Alberto; Yang, Hui; Falconieri, Veronica; Rao, Prashant; Merk, Alan; Eng, Edward T; Raczkowski, Ashleigh M; Fox, Tara; Earl, Lesley A; Patel, Dinshaw J; Subramaniam, Sriram

2017-10-05

Prokaryotic cells possess CRISPR-mediated adaptive immune systems that protect them from foreign genetic elements, such as invading viruses. A central element of this immune system is an RNA-guided surveillance complex capable of targeting non-self DNA or RNA for degradation in a sequence- and site-specific manner analogous to RNA interference. Although the complexes display considerable diversity in their composition and architecture, many basic mechanisms underlying target recognition and cleavage are highly conserved. Using cryoelectron microscopy (cryo-EM), we show that the binding of target double-stranded DNA (dsDNA) to a type I-F CRISPR system yersinia (Csy) surveillance complex leads to large quaternary and tertiary structural changes in the complex that are likely necessary in the pathway leading to target dsDNA degradation by a trans-acting helicase-nuclease. Comparison of the structure of the surveillance complex before and after dsDNA binding, or in complex with three virally encoded anti-CRISPR suppressors that inhibit dsDNA binding, reveals mechanistic details underlying target recognition and inhibition. Published by Elsevier Inc.

WRN conditioned media is sufficient for in vitro propagation of intestinal organoids from large farm and small companion animals.

PubMed

Powell, Robin H; Behnke, Michael S

2017-05-15

Recent years have seen significant developments in the ability to continuously propagate organoids derived from intestinal crypts. These advancements have been applied to mouse and human samples providing models for gastrointestinal tissue development and disease. We adapt these methods for the propagation of intestinal organoids (enteroids) from various large farm and small companion (LF/SC) animals, including cat, dog, cow, horse, pig, sheep and chicken. We show that LF/SC enteroids propagate and expand in L-WRN conditioned media containing signaling factors Wnt3a, R-spondin-3, and Noggin (WRN). Multiple successful isolations were achieved for each species, and the growth of LF/SC enteroids was maintained to high passage number. LF/SC enteroids expressed crypt stem cell marker LGR5 and low levels of mesenchymal marker VIM. Labeling with EdU also showed distinct regions of cell proliferation within the enteroids marking crypt-like regions. The ability to grow and maintain LF/SC enteroid cell lines provides additional models for the study of gastrointestinal developmental biology as well as platforms for the study of host-pathogen interactions between intestinal cells and zoonotic enteric pathogens of medical importance. © 2017. Published by The Company of Biologists Ltd.

Stardust Interstellar Preliminary Examination V: XRF Analyses of Interstellar Dust Candidates at ESRF ID13

NASA Technical Reports Server (NTRS)

Brenker, Frank E.; Westphal, Andrew J.; Simionovici, Alexandre S.; Flynn, George J.; Gainsforth, Zack; Allen, Carlton C.; Sanford, Scott; Zolensky, Michael E.; Bastien, Ron K.; Frank, David R.

2014-01-01

Here, we report analyses by synchrotron X-ray fluorescence microscopy of the elemental composition of eight candidate impact features extracted from the Stardust Interstellar Dust Collector (SIDC). Six of the features were unambiguous tracks, and two were crater-like features. Five of the tracks are so-called midnight tracks that is, they had trajectories consistent with an origin either in the interstellar dust stream or as secondaries from impacts on the Sample Return Capsule (SRC). In a companion paper reporting synchrotron X-ray diffraction analyses of ISPE candidates, we show that two of these particles contain natural crystalline materials: the terminal particle of track 30contains olivine and spinel, and the terminal particle of track 34 contains olivine. Here, we show that the terminal particle of track 30, Orion, shows elemental abundances, normalized to Fe, that are close to CI values, and a complex, fine-grained structure. The terminal particle of track 34, Hylabrook, shows abundances that deviate strongly from CI, but shows little fine structure and is nearly homogenous. The terminal particles of other midnight tracks, 29 and 37, had heavy element abundances below detection threshold. A third, track28, showed a composition inconsistent with an extraterrestrial origin, but also inconsistent with known spacecraft materials. A sixth track, with a trajectory consistent with secondary ejecta from an impact on one of the spacecraft solar panels, contains abundant Ce and Zn. This is consistent with the known composition of the glass covering the solar panel. Neither crater-like feature is likely to be associated with extraterrestrial materials. We also analyzed blank aerogel samples to characterize background and variability between aerogel tiles. We found significant differences in contamination levels and compositions, emphasizing the need for local background subtraction for accurate quantification.

Assessing future vent opening locations at the Somma-Vesuvio volcanic complex: 1. A new information geodatabase with uncertainty characterizations

NASA Astrophysics Data System (ADS)

Tadini, A.; Bisson, M.; Neri, A.; Cioni, R.; Bevilacqua, A.; Aspinall, W. P.

2017-06-01

This study presents new and revised data sets about the spatial distribution of past volcanic vents, eruptive fissures, and regional/local structures of the Somma-Vesuvio volcanic system (Italy). The innovative features of the study are the identification and quantification of important sources of uncertainty affecting interpretations of the data sets. In this regard, the spatial uncertainty of each feature is modeled by an uncertainty area, i.e., a geometric element typically represented by a polygon drawn around points or lines. The new data sets have been assembled as an updatable geodatabase that integrates and complements existing databases for Somma-Vesuvio. The data are organized into 4 data sets and stored as 11 feature classes (points and lines for feature locations and polygons for the associated uncertainty areas), totaling more than 1700 elements. More specifically, volcanic vent and eruptive fissure elements are subdivided into feature classes according to their associated eruptive styles: (i) Plinian and sub-Plinian eruptions (i.e., large- or medium-scale explosive activity); (ii) violent Strombolian and continuous ash emission eruptions (i.e., small-scale explosive activity); and (iii) effusive eruptions (including eruptions from both parasitic vents and eruptive fissures). Regional and local structures (i.e., deep faults) are represented as linear feature classes. To support interpretation of the eruption data, additional data sets are provided for Somma-Vesuvio geological units and caldera morphological features. In the companion paper, the data presented here, and the associated uncertainties, are used to develop a first vent opening probability map for the Somma-Vesuvio caldera, with specific attention focused on large or medium explosive events.

Characterization of the Fine Specificity of Bovine CD8 T-Cell Responses to Defined Antigens from the Protozoan Parasite Theileria parva▿

PubMed Central

Graham, Simon P.; Pellé, Roger; Yamage, Mat; Mwangi, Duncan M.; Honda, Yoshikazu; Mwakubambanya, Ramadhan S.; de Villiers, Etienne P.; Abuya, Evelyne; Awino, Elias; Gachanja, James; Mbwika, Ferdinand; Muthiani, Anthony M.; Muriuki, Cecelia; Nyanjui, John K.; Onono, Fredrick O.; Osaso, Julius; Riitho, Victor; Saya, Rosemary M.; Ellis, Shirley A.; McKeever, Declan J.; MacHugh, Niall D.; Gilbert, Sarah C.; Audonnet, Jean-Christophe; Morrison, W. Ivan; van der Bruggen, Pierre; Taracha, Evans L. N.

2008-01-01

Immunity against the bovine intracellular protozoan parasite Theileria parva has been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine. To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements. Nine epitopes in six T. parva antigens, together with their respective MHC restriction elements, were successfully identified. Five of the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of previously described alleles, and four were restricted by four novel restriction elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of cattle carrying the defined restriction elements and immunized with live parasites demonstrated that, with one exception, the epitopes were consistently recognized by animals of the respective genotypes. The analysis of responses was extended to animals immunized with multiple antigens delivered in separate vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24 immunized cattle. All responder cattle mounted responses specific for antigens for which they carried an identified restriction element. By contrast, only 8 of 19 responder cattle displayed a response to antigens for which they did not carry an identified restriction element. These data demonstrate that the identified antigens are inherently dominant in animals with the corresponding MHC genotypes. PMID:18070892

Use of the parameterised finite element method to robustly and efficiently evolve the edge of a moving cell.

PubMed

Neilson, Matthew P; Mackenzie, John A; Webb, Steven D; Insall, Robert H

2010-11-01

In this paper we present a computational tool that enables the simulation of mathematical models of cell migration and chemotaxis on an evolving cell membrane. Recent models require the numerical solution of systems of reaction-diffusion equations on the evolving cell membrane and then the solution state is used to drive the evolution of the cell edge. Previous work involved moving the cell edge using a level set method (LSM). However, the LSM is computationally very expensive, which severely limits the practical usefulness of the algorithm. To address this issue, we have employed the parameterised finite element method (PFEM) as an alternative method for evolving a cell boundary. We show that the PFEM is far more efficient and robust than the LSM. We therefore suggest that the PFEM potentially has an essential role to play in computational modelling efforts towards the understanding of many of the complex issues related to chemotaxis.

45 CFR 2551.53 - Under what circumstances may a Senior Companion's service be terminated?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Under what circumstances may a Senior Companion's... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Terms of Service § 2551.53 Under what circumstances may a Senior Companion's service be terminated? (a) A sponsor...

45 CFR 2551.102 - What are the conditions of service of non-stipended Senior Companions?

Code of Federal Regulations, 2010 CFR

2010-10-01

...-stipended Senior Companions? 2551.102 Section 2551.102 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Non-Stipended Senior Companions. § 2551.102 What are the conditions of service of non-stipended Senior Companions? Non-stipended...

Spectroscopic planetary detection

NASA Technical Reports Server (NTRS)

Deming, Drake

1991-01-01

One of the most promising methods for the detection of extra-solar planets is the spectroscopic method, where a small Doppler shift (approx. 10 meter/sec) in the spectrum of the parent star reveals the presence of planetary companions. However, solar type stars may show spurious Doppler shifts due to surface activity. If these effects are periodic, as is the solar activity cycle, then they may masquerade as planetary companions. The goal of this study was to determine whether the solar cycle affects the Doppler stability of integrated sunlight. Observations of integrated sunlight were made in the near infrared (approx. 2 micron), using the Kitt Peak McMath Fourier transform spectrometer, with a N2O gas absorption cell for calibration. An accuracy of approx. 5 meter/sec was achieved.

Evaluation of cross-protection by immunization with an experimental trivalent companion animal periodontitis vaccine in the mouse periodontitis model.

PubMed

Hardham, John; Sfintescu, Cornelia; Evans, Richard T

2008-03-01

Companion animal periodontal disease is one of the most prevalent diseases seen by veterinarians. The goal of this study was to evaluate the vaccine performance of a trivalent canine periodontitis vaccine in the mouse oral challenge model of periodontitis. Mice vaccinated subcutaneously with an inactivated, whole-cell vaccine preparation of Porphyromonas denticanis, Porphyromonas gulae, and Porphyromonas salivosa displayed significantly reduced alveolar bone loss in response to heterologous and cross-species challenges as compared to sham vaccinated animals. Based on the results of these studies, a periodontitis vaccine may be a useful tool in preventing the initiation and progression of periodontitis caused by the most commonly isolated pigmenting anaerobic bacteria in animals.

The algebraic theory of latent projectors in lambda matrices

NASA Technical Reports Server (NTRS)

Denman, E. D.; Leyva-Ramos, J.; Jeon, G. J.

1981-01-01

Multivariable systems such as a finite-element model of vibrating structures, control systems, and large-scale systems are often formulated in terms of differential equations which give rise to lambda matrices. The present investigation is concerned with the formulation of the algebraic theory of lambda matrices and the relationship of latent roots, latent vectors, and latent projectors to the eigenvalues, eigenvectors, and eigenprojectors of the companion form. The chain rule for latent projectors and eigenprojectors for the repeated latent root or eigenvalues is given.

Communication: An important element of maintenance and repair

NASA Technical Reports Server (NTRS)

Tripp, James S.

1992-01-01

People from the airlines, the FAA, and the manufacturers have worked together in an effort to improve the Service Difficulty Reporting system. Their work to date is summarized as follows: (1) design a worldwide reporting system to provide safety alerts to aircraft operators, manufacturers, repair facilities, and regulatory authorities; (2) design a companion system to provide worldwide reliability experience; and (3) overhaul regulatory requirements to be consistent with (1) and (2) to provide information necessary and useful for public consumption.

Companion diagnostics: a regulatory perspective from the last 5 years of molecular companion diagnostic approvals.

PubMed

Roscoe, Donna M; Hu, Yun-Fu; Philip, Reena

2015-01-01

Companion diagnostics are essential for the safe and effective use of the corresponding therapeutic products. The US FDA has approved a number of companion diagnostics used to select cancer patients for treatment with contemporaneously approved novel therapeutics. The processes of co-development and co-approval of a therapeutic product and its companion diagnostic have been a learning experience that continues to evolve. Using several companion diagnostics as examples, this article describes the challenges associated with the scientific, clinical and regulatory hurdles faced by FDA and industry alike. Taken together, this discussion is intended to assist manufacturers toward a successful companion diagnostics development plan.

Biological study of the effect of water soluble [N-(2-hydroxybenzyl)-L-aspartato] gallium complexes on breast carcinoma and fibrosarcoma cells.

PubMed

Mohsen, Ahmed; Saby, Charles; Collery, Philippe; Sabry, Gilane Mohamed; Hassan, Rasha Elsherif; Badawi, Abdelfattah; Jeannesson, Pierre; Desmaële, Didier; Morjani, Hamid

2016-10-01

Two water soluble gallium complexes described as [Ga(III)LCl], where L is the deprotonated form of N-2-hydroxybenzyl aspartic acid derivatives, were synthesized and characterized by (1)H NMR, (13)C NMR, FT-IR, mass spectrometry, and elemental analysis. The 2-(5-chloro-2-hydroxybenzylamino)succinic acid derivative (GS2) has been found to be a promising anticancer drug candidate. This compound was found to be more cytotoxic against human breast carcinoma MDA-MB231 and fibrosarcoma HT-1080 cell lines than the unsubstituted derivative and GaCl3. GS2 was able to induce apoptosis through downregulation of AKT phosphorylation, G2M arrest in cell cycle, and caspase 3/7 pathway. This gallium complex was found to induce an increase in mitochondrial ROS level in HT-1080 cells but not in MDA-MB231 cells. This suggests that the mechanism of action of GS2 would not be mediated by the drug-induced oxidative stress but probably by directly and indirectly inhibiting the AKT cell-signaling pathway.

The aryl hydrocarbon receptor and glucocorticoid receptor interact to activate human metallothionein 2A

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sato, Shoko, E-mail: satosho@rs.tus.ac.jp; Shirakawa, Hitoshi, E-mail: shirakah@m.tohoku.ac.jp; Tomita, Shuhei, E-mail: tomita@med.tottori-u.ac.jp

2013-11-15

Although the aryl hydrocarbon receptor (AHR) and glucocorticoid receptor (GR) play essential roles in mammalian development, stress responses, and other physiological events, crosstalk between these receptors has been the subject of much debate. Metallothioneins are classic glucocorticoid-inducible genes that were reported to increase upon treatment with AHR agonists in rodent tissues and cultured human cells. In this study, the mechanism of human metallothionein 2A (MT2A) gene transcription activation by AHR was investigated. Cotreatment with 3-methylcholanthrene and dexamethasone, agonists of AHR and GR respectively, synergistically increased MT2A mRNA levels in HepG2 cells. MT2A induction was suppressed by RNA interference against AHRmore » or GR. Coimmunoprecipitation experiments revealed a physical interaction between AHR and GR proteins. Moreover, chromatin immunoprecipitation assays indicated that AHR was recruited to the glucocorticoid response element in the MT2A promoter. Thus, we provide a novel mechanism whereby AHR modulates expression of human MT2A via the glucocorticoid response element and protein–protein interactions with GR. - Highlights: • Aryl hydrocarbon receptor forms a complex with glucocorticoid receptor in cells. • Human metallothionein gene is regulated by the AHR and GR interaction. • AHR–GR complex binds to glucocorticoid response element in metallothionein gene. • We demonstrated a novel transcriptional mechanism via AHR and GR interaction.« less

Three dimensional magnetic fields in extra high speed modified Lundell alternators computed by a combined vector-scalar magnetic potential finite element method

NASA Technical Reports Server (NTRS)

Demerdash, N. A.; Wang, R.; Secunde, R.

1992-01-01

A 3D finite element (FE) approach was developed and implemented for computation of global magnetic fields in a 14.3 kVA modified Lundell alternator. The essence of the new method is the combined use of magnetic vector and scalar potential formulations in 3D FEs. This approach makes it practical, using state of the art supercomputer resources, to globally analyze magnetic fields and operating performances of rotating machines which have truly 3D magnetic flux patterns. The 3D FE-computed fields and machine inductances as well as various machine performance simulations of the 14.3 kVA machine are presented in this paper and its two companion papers.

WR 148 and the not so compact companion

NASA Astrophysics Data System (ADS)

Munoz, Melissa; Moffat, Anthony J.; Hill, Grant M.; Shenar, Tomer; Richardson, Noel D.; Pablo, Herbert; St-Louis, Nicole; Ramiaramanantsoa, Tahina

2017-11-01

The objective is to determine the nature of the unseen companion of the single-lined spectroscopic binary, WR 148 (= WN7h+?). The absence of companion lines supports a compact companion (cc) scenario. The lack of hard X-rays favours a non-compact companion scenario. Is WR 148 a commonplace WR+OB binary or a rare WR+cc binary?

Apoplastic and symplastic phloem loading in Quercus robur and Fraxinus excelsior

PubMed Central

Lohaus, Gertrud

2014-01-01

Whereas most of the research on phloem loading is performed on herbaceous plants, less is known about phloem loading strategies in trees. In this study, the phloem loading mechanisms of Quercus robur and Fraxinus excelsior were analysed. The following features were examined: the minor vein structure, the sugar concentrations in phloem sap by the laser–aphid–stylet technique, the distribution of photoassimilates in the mesophyll cells by non-aqueous fractionation, gradients of sugar concentrations and osmotic pressure, and the expression of sucrose transporters. The minor vein configurations of Q. robur and F. excelsior belong to the open type. Quercus robur contained companion cells in the minor veins whereas F. excelsior showed intermediary cells in addition to ordinary companion cells. The main carbon transport form in Q. robur was sucrose (~1M). In F. excelsior high amounts of raffinose and stachyose were also transported. However, in both tree species, the osmolality of phloem sap was higher than the osmolality of the mesophyll cells. The concentration gradients between phloem sap and the cytoplasm of mesophyll cells for sucrose were 16-fold and 14-fold for Q. robur and F. excelsior, respectively. Independent of the type of translocated sugars, sucrose transporter cDNAs were cloned from both species. The results indicate that phloem loading of sucrose and other metabolites must involve active loading steps in both tree species. Quercus robur seems to be an apoplastic phloem loader while F. excelsior shows indications of being a symplastic or mixed symplastic–apoplastic phloem loader. PMID:24591056

Critical elements in the development of cell therapy potency assays for ischemic conditions.

PubMed

Porat, Yael; Abraham, Eytan; Karnieli, Ohad; Nahum, Sagi; Woda, Juliana; Zylberberg, Claudia

2015-07-01

A successful potency assay for a cell therapy product (CTP) used in the treatment of ischemic conditions should quantitatively measure relevant biological properties that predict therapeutic activity. This is especially challenging because of numerous degrees of complexity stemming from factors that include a multifactorial complex mechanism of action, cell source, inherent cell characteristics, culture method, administration mode and the in vivo conditions to which the cells are exposed. The expected biological function of a CTP encompasses complex interactions that range from a biochemical, metabolic or immunological activity to structural replacement of damaged tissue or organ. Therefore, the requirements for full characterization of the active substance with respect to biological function could be taxing. Moreover, the specific mechanism of action is often difficult to pinpoint to a specific molecular entity; rather, it is more dependent on the functionality of the cellular components acting in a in a multifactorial fashion. In the case of ischemic conditions, the cell therapy mechanism of action can vary from angiogenesis, vasculogenesis and arteriogenesis that may activate different pathways and clinical outcomes. The CTP cellular attributes with relation to the suggested mechanism of action can be used for the development of quantitative and reproducible analytical potency assays. CTPs selected and released on the basis of such potency assays should have the highest probability of providing meaningful clinical benefit for patients. This White Paper will discuss and give examples for key elements in the development of a potency assay for treatment of ischemic disorders treated by the use of CTPs. Copyright © 2015 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Bifunctional Platinum(II) Complexes with Bisphosphonates Substituted Diamine Derivatives: Synthesis and In vitro Cytotoxicity.

PubMed

Sun, Yanyan; Zhao, Jian; Ji, Zhongling

2017-12-01

A series of N,N'-dibisphosphonate-containing 1,3-propanediamine derivatives (L1 - L6) and their corresponding dichloridoplatinum(II) complexes (1 - 6) have been synthesized and characterized by elemental analysis, 1 H-NMR, 13 C-NMR, 31 P-NMR and HR-MS spectra. The in vitro antitumor activities of compounds L1 - L6 and 1 - 6 were tested by WST-8 assay with Cell Counting Kit-8, indicating that platinum-based complexes 1 - 6 showed higher cytotoxicity than corresponding ligands L1 - L6 against A549 and MG-63, especially complex 2 which displayed comparable cytotoxicity to those of cisplatin and zoledronate after 48 h incubation. In addition, complexes 1 - 6 were more active in vitro on osteosarcoma cell line MG-63 than normal osteoblast cell line hFOB 1.19. The structure-activity relationship has been summarized based on the in vitro cytotoxicity of three series of platinum complexes from this and our previous studies. The in vitro bone affinity of platinum complexes was also tested by hydroxyapatite (HAP) chromatography in terms of capacity factor K'. Besides, in this paper, representative complex 2, which has been proved to be a promising antitumor agent with high cytotoxicity and bone HAP binding property, was investigated for its mechanism of action producing cell death against MG-63. © 2017 Wiley-VHCA AG, Zurich, Switzerland.

In vitro anticancer activities of Schiff base and its lanthanum complex

NASA Astrophysics Data System (ADS)

Neelima; Poonia, Kavita; Siddiqui, Sahabjada; Arshad, Md; Kumar, Dinesh

2016-02-01

Schiff base metal complexes are well-known to intercalate DNA. The La(III) complexes have been synthesized such that they hinder with the role of the topoisomerases, which control the topology of DNA during the cell-division cycle. Although several promising chemotherapeutics have been developed, on the basis of Schiff base metal complex DNA intercalating system they did not proceed past clinical trials due to their dose-limiting toxicity. Herein, we discuss an alternative compound, the La(III) complex, [La(L1)2Cl3]·7H2O based on a Schiff base ligand 2,3-dihydro-1H-indolo-[2,3-b]-phenazin-4(5H)-ylidene)benzothiazole-2-amine (L1), and report in vitro cell studies. Results of antitumor activity using cell viability assay, reactive oxygen species (ROS) generation and nuclear condensation in PC-3 (Human, prostate carcinoma) cells show that the metal complex is more potent than ligand. La(III) complexes have been synthesized by reaction of lanthanum(III) salt in 1:2 M ratio with ligands L1 and 3-(ethoxymethylene)-2,3-dihydro-1H-indolo[2,3-b]-phenazin-4(5H)-ylidene)benzathiazole-2-amine (L2) in methanol. The ligands and their La(III) complexes were characterized by molar conductance, magnetic susceptibility, elemental analyses, FT-IR, UV-Vis, 1H/13C NMR, thermogravimetric, XRD, and SEM analysis.

Carbohydrate linked organotin(IV) complexes as human topoisomerase Iα inhibitor and their antiproliferative effects against the human carcinoma cell line.

PubMed

Khan, Rais Ahmad; Yadav, Shipra; Hussain, Zahid; Arjmand, Farukh; Tabassum, Sartaj

2014-02-14

Dimethyltin(IV) complexes with ethanolamine (1) and biologically significant N-glycosides (2 and 3) were designed and synthesized. The structural elucidation of complexes 1-3 was done using elemental and spectroscopic methods; in addition, complex 1 was studied by single crystal X-ray diffraction studies. The in vitro DNA binding profile of complexes 2 and 3 was carried out by employing different biophysical methods to ascertain the feasibility of glycosylated complexes. Further, the cleaving ability of 2 and 3 was investigated by the agarose gel electrophoretic mobility assay with supercoiled pBR322 DNA, and demonstrated significantly good nuclease activity. Furthermore, both the complexes exhibited significant inhibitory effects on the catalytic activity of human Topo I at lower concentration than standard drugs. Computer-aided molecular docking techniques were used to ascertain the mode and mechanism of action towards the molecular target DNA and Topo I. The cytotoxicity of 2 and 3 against human hepatoma cancer cells (Huh7) was evaluated, which revealed significant regression in cancerous cells as compared with the standard drug. The antiproliferative activities of 2 and 3 were tested against human hepatoma cancer cells (Huh7), and results showed significantly good activity. Additionally, to validate the remarkable antiproliferative activity of complexes 2 and 3, specific regulatory gene expression (MMP-2 and TGF-β) was obtained by real time PCR.

High Fractional Occupancy of a Tandem Maf Recognition Element and Its Role in Long-Range β-Globin Gene Regulation

PubMed Central

Stees, Jared R.; Hossain, Mir A.; Sunose, Tomoki; Kudo, Yasushi; Pardo, Carolina E.; Nabilsi, Nancy H.; Darst, Russell P.; Poudyal, Rosha; Igarashi, Kazuhiko; Kladde, Michael P.

2015-01-01

Enhancers and promoters assemble protein complexes that ultimately regulate the recruitment and activity of RNA polymerases. Previous work has shown that at least some enhancers form stable protein complexes, leading to the formation of enhanceosomes. We analyzed protein-DNA interactions in the murine β-globin gene locus using the methyltransferase accessibility protocol for individual templates (MAPit). The data show that a tandem Maf recognition element (MARE) in locus control region (LCR) hypersensitive site 2 (HS2) reveals a remarkably high degree of occupancy during differentiation of mouse erythroleukemia cells. Most of the other transcription factor binding sites in LCR HS2 or in the adult β-globin gene promoter regions exhibit low fractional occupancy, suggesting highly dynamic protein-DNA interactions. Targeting of an artificial zinc finger DNA-binding domain (ZF-DBD) to the HS2 tandem MARE caused a reduction in the association of MARE-binding proteins and transcription complexes at LCR HS2 and the adult βmajor-globin gene promoter but did not affect expression of the βminor-globin gene. The data demonstrate that a stable MARE-associated footprint in LCR HS2 is important for the recruitment of transcription complexes to the adult βmajor-globin gene promoter during erythroid cell differentiation. PMID:26503787

Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments.

PubMed

Regier, Mary C; Maccoux, Lindsey J; Weinberger, Emma M; Regehr, Keil J; Berry, Scott M; Beebe, David J; Alarid, Elaine T

2016-08-01

Heterotypic interactions in cancer microenvironments play important roles in disease initiation, progression, and spread. Co-culture is the predominant approach used in dissecting paracrine interactions between tumor and stromal cells, but functional results from simple co-cultures frequently fail to correlate to in vivo conditions. Though complex heterotypic in vitro models have improved functional relevance, there is little systematic knowledge of how multi-culture parameters influence this recapitulation. We therefore have employed a more iterative approach to investigate the influence of increasing model complexity; increased heterotypic complexity specifically. Here we describe how the compartmentalized and microscale elements of our multi-culture device allowed us to obtain gene expression data from one cell type at a time in a heterotypic culture where cells communicated through paracrine interactions. With our device we generated a large dataset comprised of cell type specific gene-expression patterns for cultures of increasing complexity (three cell types in mono-, co-, or tri-culture) not readily accessible in other systems. Principal component analysis indicated that gene expression was changed in co-culture but was often more strongly altered in tri-culture as compared to mono-culture. Our analysis revealed that cell type identity and the complexity around it (mono-, co-, or tri-culture) influence gene regulation. We also observed evidence of complementary regulation between cell types in the same heterotypic culture. Here we demonstrate the utility of our platform in providing insight into how tumor and stromal cells respond to microenvironments of varying complexities highlighting the expanding importance of heterotypic cultures that go beyond conventional co-culture.

Coordination behavior of tetraaza [N4] ligand towards Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes: Synthesis, spectroscopic characterization and anticancer activity

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.

2012-11-01

Novel eight Co(II), Ni(II), Cu(II), Cu(I) and Pd(II) complexes with [N4] ligand (L) i.e. 2-amino-N-{2-[(2-aminobenzoyl)amino]ethyl}benzamide have been synthesized and structurally characterized by elemental analysis, spectral, thermal (TG/DTG), magnetic, and molar conductivity measurements. On the basis of IR, mass, electronic and EPR spectral studies an octahedral geometry has been proposed for Co(II), Ni(II) complexes and Cu(II) chloride complex, square-pyramidal for Cu(I) bromide complex. For Cu(II) nitrate complex (6), Pd(II) complex (8) square planar geometry was proposed. The EPR data of Cu(II) complexes in powdered form indicate dx2-y2 ground state of Cu(II) ion. The antitumor activity of the synthesized ligand and some selected metal complexes has been studied. The palladium(II) complex (8) was found to display cytotoxicity (IC50 = 25.6 and 41 μM) against human breast cancer cell line MCF-7 and human hepatocarcinoma HEPG2 cell line.

Transcriptome dynamics and molecular cross-talk between bovine oocyte and its companion cumulus cells

PubMed Central

2011-01-01

Background The bi-directional communication between the oocyte and its companion cumulus cells (CCs) is crucial for development and functions of both cell types. Transcripts that are exclusively expressed either in oocytes or CCs and molecular mechanisms affected due to removal of the communication axis between the two cell types is not investigated at a larger scale. The main objectives of this study were: 1. To identify transcripts exclusively expressed either in oocyte or CCs and 2. To identify those which are differentially expressed when the oocyte is cultured with or without its companion CCs and vice versa. Results We analyzed transcriptome profile of different oocyte and CC samples using Affymetrix GeneChip Bovine Genome array containing 23000 transcripts. Out of 13162 genes detected in germinal vesicle (GV) oocytes and their companion CCs, 1516 and 2727 are exclusively expressed in oocytes and CCs, respectively, while 8919 are expressed in both. Similarly, of 13602 genes detected in metaphase II (MII) oocytes and CCs, 1423 and 3100 are exclusively expressed in oocytes and CCs, respectively, while 9079 are expressed in both. A total of 265 transcripts are differentially expressed between oocytes cultured with (OO + CCs) and without (OO - CCs) CCs, of which 217 and 48 are over expressed in the former and the later groups, respectively. Similarly, 566 transcripts are differentially expressed when CCs mature with (CCs + OO) or without (CCs - OO) their enclosed oocytes. Of these, 320 and 246 are over expressed in CCs + OO and CCs - OO, respectively. While oocyte specific transcripts include those involved in transcription (IRF6, POU5F1, MYF5, MED18), translation (EIF2AK1, EIF4ENIF1) and CCs specific ones include those involved in carbohydrate metabolism (HYAL1, PFKL, PYGL, MPI), protein metabolic processes (IHH, APOA1, PLOD1), steroid biosynthetic process (APOA1, CYP11A1, HSD3B1, HSD3B7). Similarly, while transcripts over expressed in OO + CCs are involved in carbohydrate metabolism (ACO1, 2), molecular transport (GAPDH, GFPT1) and nucleic acid metabolism (CBS, NOS2), those over expressed in CCs + OO are involved in cellular growth and proliferation (FOS, GADD45A), cell cycle (HAS2, VEGFA), cellular development (AMD1, AURKA, DPP4) and gene expression (FOSB, TGFB2). Conclusion In conclusion, this study has generated large scale gene expression data from different oocyte and CCs samples that would provide insights into gene functions and interactions within and across different pathways that are involved in the maturation of bovine oocytes. Moreover, the presence or absence of oocyte and CC factors during bovine oocyte maturation can have a profound effect on transcript abundance of each cell types, thereby showing the prevailing molecular cross-talk between oocytes and their corresponding CCs. PMID:21261964

Pathogenesis and micro-anatomic characterization of a cell-adapted mutant foot-and-mouth disease virus in cattle: impact of the Jumonji C-domain containing protein 6 (JMJD6) and route of innoculation

USDA-ARS?s Scientific Manuscript database

In a companion study, we reported that the cellular Jumonji-C Domain containing Protein 6 (JMJD6) protein is involved in an alternate integrin- and HS-independent pathway of FMDV infection in CHO cells. Here, we investigated the JMJD6 localization in animal tissues from cattle infected with either ...

45 CFR 2551.45 - Is a Senior Companion a federal employee, an employee of the sponsor or of the volunteer station?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false Is a Senior Companion a federal employee, an... Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Eligibility, Status, and Cost Reimbursements § 2551.45 Is a Senior Companion a...

45 CFR 2551.51 - What are the terms of service of a Senior Companion?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 45 Public Welfare 4 2010-10-01 2010-10-01 false What are the terms of service of a Senior...) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion Terms of Service § 2551.51 What are the terms of service of a Senior Companion? A Senior Companion shall serve a minimum...

Synthesis, characterization, DNA-binding study and anticancer properties of ternary metal(II) complexes of edda and an intercalating ligand.

PubMed

Ng, Chew Hee; Kong, King Chow; Von, Sze Tin; Balraj, Pauline; Jensen, Paul; Thirthagiri, Eswary; Hamada, Hirokazu; Chikira, Makoto

2008-01-28

A series of ternary metal(ii) complexes {M(phen)(edda); 1a (Cu), 1b (Co), 1c (Zn), 1d (Ni); H(2)edda = N,N(')-ethylenediaminediacetic acid} of N,N'-ethylene-bridged diglycine and 1,10-phenanthroline were synthesized and characterized by elemental analysis, FTIR, UV-visible spectroscopy and magnetic susceptibility measurement. The interaction of these complexes with DNA was investigated using CD and EPR spectroscopy. MTT assay results of 1a-1c , screened on MCF-7 cancer cell lines, show that synergy between the metal and ligands results in significant enhancement of their antiproliferative properties. Preliminary results from apoptosis and cell cycle analyses with flow cytometry are reported. seems to be able to induce cell cycle arrest at G(0)/G(1). The crystal structure of 1a is also included.

Transforming Growth Factor β Suppresses Peroxisome Proliferator–Activated Receptor γ Expression via Both SMAD Binding and Novel TGF-β Inhibitory Elements

PubMed Central

Lakshmi, Sowmya P.; Reddy, Aravind T.; Reddy, Raju C.

2017-01-01

Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other’s expression, and such PPARγ downregulation is prominent in fibrosis and mediated, via previously unknown SMAD-signaling mechanisms. Here we show that TGF-β induces association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive corepressors E2F4 and p107. The complex mediates TGF-β-induced repression by binding to regulatory elements in the target promoter. In the PPARG promoter, we found that the SMAD3-SMAD4 complex binds both to a previously unknown consensus TGF-β inhibitory element (TIE) and also to canonical SMAD-binding elements (SBEs). Furthermore, the TIE and SBEs independently mediated partial repression of PPARG transcription, the first demonstration of a TIE and SBEs functioning within the same promoter. Also, TGF-β-treated fibroblasts contained SMAD complexes that activated a SMAD target gene in addition to those repressing PPARG transcription, the first finding of such dual activity within the same cell. These findings describe in detail novel mechanisms by which TGF-β represses PPARG transcription, thereby facilitating its own pro-fibrotic activity. PMID:28100650

Self-assembled supramolecular hetero-bimetallacycles for anticancer potency via intracellular release

PubMed Central

Mishra, Anurag; Lee, Seung Chang; Kaushik, Neha; Cook, Timothy R.; Choi, Eun Ha

2015-01-01

Two new tetracationic hetero-bimetallacycles, 4 and 5, have been constructed from an N,N′-bis(4-(pyridin-4-ylethynyl)phenyl)pyridine-2,6-dicarboxamide ligand, 1, and cis-blocked complexes [M(dppf)](OTf)2 (dppf = 1,1′-bis(diphenylphosphino)ferrocene; M = Pd (2), Pt (3)) in CH3NO2/CH2Cl2 (1:1) solvent. Both complexes were isolated with adequate yields as triflate salts and were then characterized using 1H, 13C, and 31P NMR spectroscopy, elemental analysis, UV-Vis spectroscopy, and high-resolution electrospray mass spectrometry (HR-ESMS). The molecular structure of 4 was determined by molecular mechanics force field calculations. The cytotoxic effect of both new complexes were analyzed against T98G (brain tumor), KB (head and neck cancer), SNU-80 (thyroid cancer), and HEK-293 non-malignant cell lines. The cytotoxicity of complexes 4 and 5 were found to be considerably more effective against cancer cells than reference drug cisplatin. Annexin-V/PI staining, caspase-3/-7 activity, reduction in mitochondrial membrane potential justify a significant level of apoptosis in complex treated cells. PMID:25209962

Nuclear Export and Expression of Human T-Cell Leukemia Virus Type 1 tax/rex mRNA Are RxRE/Rex Dependent

PubMed Central

Bai, X. T.; Sinha-Datta, U.; Ko, N. L.; Bellon, M.

2012-01-01

Human T-cell leukemia virus type 1 (HTLV-1) is a complex retrovirus associated with the lymphoproliferative disease adult T-cell leukemia/lymphoma (ATL) and the neurodegenerative disorder tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM). Replication of HTLV-1 is under the control of two major trans-acting proteins, Tax and Rex. Previous studies suggested that Tax activates transcription from the viral long terminal repeat (LTR) through recruitment of cellular CREB and transcriptional coactivators. Other studies reported that Rex acts posttranscriptionally and allows the cytoplasmic export of unspliced or incompletely spliced viral mRNAs carrying gag/pol and env only. As opposed to HIV's Rev-responsive element (RRE), the Rex-responsive element (RxRE) is present in all viral mRNAs in HTLV-1. However, based on indirect observations, it is believed that nuclear export and expression of the doubly spliced tax/rex RNA are Rex independent. In this study, we demonstrate that Rex does stimulate Tax expression, through nuclear-cytoplasmic export of the tax/rex RNA, even though a Rex-independent basal export mechanism exists. This effect was dependent upon the RxRE element and the RNA-binding activity of Rex. In addition, Rex-mediated export of tax/rex RNA was CRM1 dependent and inhibited by leptomycin B treatment. RNA immunoprecipitation (RNA-IP) experiments confirmed Rex binding to the tax/rex RNA in both transfected cells with HTLV-1 molecular clones and HTLV-1-infected T cells. Since both Rex and p30 interact with the tax/rex RNA and with one another, this may offer a temporal and dynamic regulation of HTLV-1 replication. Our results shed light on HTLV-1 replication and reveal a more complex regulatory network than previously anticipated. PMID:22318152

Abundances in the Uranium-rich Star CS 31082-001

NASA Astrophysics Data System (ADS)

Qian, Y.-Z.; Wasserburg, G. J.

2001-05-01

The recent discovery by Cayrel et al. of U in CS 31082-001 along with Os and Ir at greatly enhanced abundances but with [Fe/H]=-2.9 strongly reinforces the argument that there are at least two kinds of Type II supernova (SN II) sources for r-nuclei. One source is the high-frequency H events responsible for heavy r-nuclei (A>135) but not Fe. The H-yields calculated from data on other ultra-metal-poor stars and the Sun provide a template for quantitatively predicting the abundances of all other r-elements. In CS 31082-001 these should show a significant deficiency at A<135 relative to the solar r-pattern. It is proposed that CS 31082-001 should have had a companion that exploded as an SN II H event. If the binary survived the explosion, this star should now have a compact companion, most likely a stellar-mass black hole. Comparison of abundance data with predicted values and a search for a compact companion should provide a stringent test of the proposed r-process model. The U-Th age determined by Cayrel et al. for CS 31082-001 is, to within substantial uncertainties, in accord with the r-process age determined from solar system data. The time gap between the big bang and the onset of normal star formation allows r-process chronometers to provide only a lower limit on the age of the universe.

Social support during delivery in rural central Ghana: a mixed methods study of women's preferences for and against inclusion of a lay companion in the delivery room.

PubMed

Alexander, Amir; Mustafa, Aesha; Emil, Sarah A V; Amekah, Ebenezer; Engmann, Cyril; Adanu, Richard; Moyer, Cheryl A

2014-09-01

This study aimed to explore pregnant women's attitudes towards the inclusion of a lay companion as a source of social support during labour and delivery in rural central Ghana. Quantitative demographic and pregnancy-related data were collected from 50 pregnant women presenting for antenatal care at a rural district hospital and analysed using STATA/IC 11.1. Qualitative attitudinal questions were collected from the same women through semi-structured interviews; data were analysed using NVivo 9.0. Twenty-nine out of 50 women (58%) preferred to have a lay companion during facility-based labour and delivery, whereas 21 (42%) preferred to deliver alone with the nurses in a facility. Women desiring a companion were younger, had more antenatal care visits, had greater educational attainment and were likely to be experiencing their first delivery. Women varied in the type of companion they prefer (male partner vs female relative). What was expected in terms of social support differed based upon the type of companion. Male companions were expected to provide emotional support and to 'witness her pain'. Female companions were expected to provide emotional support as well as instrumental, informational and appraisal support. Three qualitative themes were identified that run counter to the inclusion of a lay helper: fear of an evil-spirited companion, a companion not being necessary or helpful, and being 'too shy' of a companion. This research challenges the assumption of a unilateral desire for social support during labour and delivery, and suggests that women differ in the type of companion and type of support they prefer during facility deliveries. Future research is needed to determine the direction of the relationship--whether women desire certain types of support and thus choose companions they believe can meet those needs, or whether women desire a certain companion and adjust their expectations accordingly.

Increasing lanthanide luminescence by use of the RETEL effect.

PubMed

Leif, Robert C; Vallarino, Lidia M; Becker, Margie C; Yang, Sean

2006-08-01

Luminescent lanthanide complexes produce emissions with the narrowest-known width at half maximum; however, their significant use in cytometry required an increase in luminescence intensity. The companion review, Leif et al., Cytometry 2006;69A:767-778, described a new technique for the enhancement of lanthanide luminescence, the Resonance Energy Transfer Enhanced Luminescence (RETEL) effect, which increases luminescence and is compatible with standard slide microscopy. The luminescence of the europium ion macrocyclic complex, EuMac, was increased by employing the RETEL effect. After adding the nonluminescent gadolinium ion complex of the thenoyltrifluoroacetonate (TTFA) ligand or the sodium salt of TTFA in ethanol solution, the EuMac-labeled sample was allowed to dry. Both a conventional arc lamp and a time-gated UV LED served as light sources for microscopic imaging. The emission intensity was measured with a CCD camera. Multiple time-gated images were summed with special software to permit analysis and effective presentation of the final image. With the RETEL effect, the luminescence of the EuMac-streptavidin conjugate increased at least six-fold upon drying. Nuclei of apoptotic cells were stained with DAPI and tailed with 5BrdUrd to which a EuMac-anti-5BrdU conjugate was subsequently attached. Time-gated images showed the long-lived EuMac luminescence but did not show the short-lived DAPI fluorescence. Imaging of DNA-synthesizing cells with an arc lamp showed that both S phase and apoptotic cells were labeled, and that their labeling patterns were different. The images of the luminescent EuMac and fluorescent DAPI were combined to produce a color image on a white background. This combination of simple chemistry, instrumentation, and presentation should make possible the inexpensive use of the lanthanide macrocycles, Quantum Dyes, as molecular diagnostics for cytological and histopathological microscopic imaging. (c) 2006 International Society for Analytical Cytology.

Modal element method for potential flow in non-uniform ducts: Combining closed form analysis with CFD

NASA Technical Reports Server (NTRS)

Baumeister, Kenneth J.; Baumeister, Joseph F.

1994-01-01

An analytical procedure is presented, called the modal element method, that combines numerical grid based algorithms with eigenfunction expansions developed by separation of variables. A modal element method is presented for solving potential flow in a channel with two-dimensional cylindrical like obstacles. The infinite computational region is divided into three subdomains; the bounded finite element domain, which is characterized by the cylindrical obstacle and the surrounding unbounded uniform channel entrance and exit domains. The velocity potential is represented approximately in the grid based domain by a finite element solution and is represented analytically by an eigenfunction expansion in the uniform semi-infinite entrance and exit domains. The calculated flow fields are in excellent agreement with exact analytical solutions. By eliminating the grid surrounding the obstacle, the modal element method reduces the numerical grid size, employs a more precise far field boundary condition, as well as giving theoretical insight to the interaction of the obstacle with the mean flow. Although the analysis focuses on a specific geometry, the formulation is general and can be applied to a variety of problems as seen by a comparison to companion theories in aeroacoustics and electromagnetics.

Resolved Companions of Cepheids as Seen by HST and XMM

NASA Astrophysics Data System (ADS)

Evans, Nancy Remage; Bond, Howard E.; Schaefer, Gail; Mason, Brian D.; Tingle, Evan; Karovska, Margarita; Pillitteri, Ignazio; Wolk, Scott J.; Guinan, Edward F.; Engle, Scott G.

2016-01-01

We have conducted a survey of 70 classical Cepheids with the Hubble Wide Field Camera3 (WFC3) to identify possible resolved companions. Data cover the range of 0.3" to 20" which typically corresponds to 200 AU to 0.1 pc. At present only possible companions greater than 5" from the Cepheid are discussed, since closer companions require a sophisticated point spread correction for the light of the much brighter Cepheid. We have followed up a subset of the possible resolved companions with XMM observations to determine whether they are young (X-ray active) enough to be physical companions of the Cepheids. We estimate that 4% of the Cepheids have a physical resolved companion, with the widest having a separation of 4000 AU. The one wider young star is in the field of S Nor, but since it is a cluster member, the companion is not assumed to be gravitationally bound to the Cepheid.

X-ray propagation microscopy of biological cells using waveguides as a quasipoint source

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giewekemeyer, K.; Krueger, S. P.; Kalbfleisch, S.

2011-02-15

We have used x-ray waveguides as highly confining optical elements for nanoscale imaging of unstained biological cells using the simple geometry of in-line holography. The well-known twin-image problem is effectively circumvented by a simple and fast iterative reconstruction. The algorithm which combines elements of the classical Gerchberg-Saxton scheme and the hybrid-input-output algorithm is optimized for phase-contrast samples, well-justified for imaging of cells at multi-keV photon energies. The experimental scheme allows for a quantitative phase reconstruction from a single holographic image without detailed knowledge of the complex illumination function incident on the sample, as demonstrated for freeze-dried cells of the eukaryoticmore » amoeba Dictyostelium discoideum. The accessible resolution range is explored by simulations, indicating that resolutions on the order of 20 nm are within reach applying illumination times on the order of minutes at present synchrotron sources.« less

Comparison of Node-Centered and Cell-Centered Unstructured Finite-Volume Discretizations: Inviscid Fluxes

NASA Technical Reports Server (NTRS)

Diskin, Boris; Thomas, James L.

2010-01-01

Cell-centered and node-centered approaches have been compared for unstructured finite-volume discretization of inviscid fluxes. The grids range from regular grids to irregular grids, including mixed-element grids and grids with random perturbations of nodes. Accuracy, complexity, and convergence rates of defect-correction iterations are studied for eight nominally second-order accurate schemes: two node-centered schemes with weighted and unweighted least-squares (LSQ) methods for gradient reconstruction and six cell-centered schemes two node-averaging with and without clipping and four schemes that employ different stencils for LSQ gradient reconstruction. The cell-centered nearest-neighbor (CC-NN) scheme has the lowest complexity; a version of the scheme that involves smart augmentation of the LSQ stencil (CC-SA) has only marginal complexity increase. All other schemes have larger complexity; complexity of node-centered (NC) schemes are somewhat lower than complexity of cell-centered node-averaging (CC-NA) and full-augmentation (CC-FA) schemes. On highly anisotropic grids typical of those encountered in grid adaptation, discretization errors of five of the six cell-centered schemes converge with second order on all tested grids; the CC-NA scheme with clipping degrades solution accuracy to first order. The NC schemes converge with second order on regular and/or triangular grids and with first order on perturbed quadrilaterals and mixed-element grids. All schemes may produce large relative errors in gradient reconstruction on grids with perturbed nodes. Defect-correction iterations for schemes employing weighted least-square gradient reconstruction diverge on perturbed stretched grids. Overall, the CC-NN and CC-SA schemes offer the best options of the lowest complexity and secondorder discretization errors. On anisotropic grids over a curved body typical of turbulent flow simulations, the discretization errors converge with second order and are small for the CC-NN, CC-SA, and CC-FA schemes on all grids and for NC schemes on triangular grids; the discretization errors of the CC-NA scheme without clipping do not converge on irregular grids. Accurate gradient reconstruction can be achieved by introducing a local approximate mapping; without approximate mapping, only the NC scheme with weighted LSQ method provides accurate gradients. Defect correction iterations for the CC-NA scheme without clipping diverge; for the NC scheme with weighted LSQ method, the iterations either diverge or converge very slowly. The best option in curved geometries is the CC-SA scheme that offers low complexity, second-order discretization errors, and fast convergence.

New spectroscopic binary companions of giant stars and updated metallicity distribution for binary systems

NASA Astrophysics Data System (ADS)

Bluhm, P.; Jones, M. I.; Vanzi, L.; Soto, M. G.; Vos, J.; Wittenmyer, R. A.; Drass, H.; Jenkins, J. S.; Olivares, F.; Mennickent, R. E.; Vučković, M.; Rojo, P.; Melo, C. H. F.

2016-10-01

We report the discovery of 24 spectroscopic binary companions to giant stars. We fully constrain the orbital solution for 6 of these systems. We cannot unambiguously derive the orbital elements for the remaining stars because the phase coverage is incomplete. Of these stars, 6 present radial velocity trends that are compatible with long-period brown dwarf companions. The orbital solutions of the 24 binary systems indicate that these giant binary systems have a wide range in orbital periods, eccentricities, and companion masses. For the binaries with restricted orbital solutions, we find a range of orbital periods of between ~97-1600 days and eccentricities of between ~0.1-0.4. In addition, we studied the metallicity distribution of single and binary giant stars. We computed the metallicity of a total of 395 evolved stars, 59 of wich are in binary systems. We find a flat distribution for these binary stars and therefore conclude that stellar binary systems, and potentially brown dwarfs, have a different formation mechanism than planets. This result is confirmed by recent works showing that extrasolar planets orbiting giants are more frequent around metal-rich stars. Finally, we investigate the eccentricity as a function of the orbital period. We analyzed a total of 130 spectroscopic binaries, including those presented here and systems from the literature. We find that most of the binary stars with periods ≲30 days have circular orbits, while at longer orbital periods we observe a wide spread in their eccentricities. Based on observations collected at La Silla - Paranal Observatory under programs IDs IDs 085.C-0557, 087.C.0476, 089.C-0524, 090.C-0345, 096.A-9020 and through the Chilean Telescope Time under programs IDs CN2012A-73, CN2012B-47, CN2013A-111, CN2013B-51, CN2014A-52 and CN2015A-48.

BET Bromodomain Inhibition Releases the Mediator Complex from Select cis-Regulatory Elements.

PubMed

Bhagwat, Anand S; Roe, Jae-Seok; Mok, Beverly Y L; Hohmann, Anja F; Shi, Junwei; Vakoc, Christopher R

2016-04-19

The bromodomain and extraterminal (BET) protein BRD4 can physically interact with the Mediator complex, but the relevance of this association to the therapeutic effects of BET inhibitors in cancer is unclear. Here, we show that BET inhibition causes a rapid release of Mediator from a subset of cis-regulatory elements in the genome of acute myeloid leukemia (AML) cells. These sites of Mediator eviction were highly correlated with transcriptional suppression of neighboring genes, which are enriched for targets of the transcription factor MYB and for functions related to leukemogenesis. A shRNA screen of Mediator in AML cells identified the MED12, MED13, MED23, and MED24 subunits as performing a similar regulatory function to BRD4 in this context, including a shared role in sustaining a block in myeloid maturation. These findings suggest that the interaction between BRD4 and Mediator has functional importance for gene-specific transcriptional activation and for AML maintenance. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

The human haptoglobin gene promoter: interleukin-6-responsive elements interact with a DNA-binding protein induced by interleukin-6.

PubMed Central

Oliviero, S; Cortese, R

1989-01-01

Transcription of the human haptoglobin (Hp) gene is induced by interleukin-6 (IL-6) in the human hepatoma cell line Hep3B. Cis-acting elements responsible for this response are localized within the first 186 bp of the 5'-flanking region. Site-specific mutants of the Hp promoter fused to the chloramphenicol acetyl transferase (CAT) gene were analysed by transient transfection into uninduced and IL-6-treated Hep3B cells. We identified three regions, A, B and C, defined by mutation, which are important for the IL-6 response. Band shift experiments using nuclear extracts from untreated or IL-6-treated cells revealed the presence of IL-6-inducible DNA binding activities when DNA fragments containing the A or the C sequences were used. Competition experiments showed that both sequences bind to the same nuclear factors. Polymers of oligonucleotides containing either the A or the C regions confer IL-6 responsiveness to a truncated SV40 promoter. The B region forms several complexes with specific DNA-binding proteins different from those which bind to the A and C region. The B region complexes are identical in nuclear extracts from IL-6-treated and untreated cells. While important for IL-6 induction in the context of the haptoglobin promoter, the B site does not confer IL-6 inducibility to the SV40 promoter. Our results indicate that the IL-6 response of the haptoglobin promoter is dependent on the presence of multiple, partly redundant, cis-acting elements. Images PMID:2787245

Alternative donor hematopoietic stem cell transplantation for sickle cell disease

PubMed Central

Eckrich, Michael J.; Epstein, Stacy; Barnhart, Carrie; Cannon, Mark; Fukes, Tracy; Hyland, Michelle; Shah, Krishna; Grochowski, Darci; Champion, Elizabeth; Ivanova, Anastasia

2017-01-01

Most patients who could be cured of sickle cell disease (SCD) with stem cell transplantation do not have a matched sibling donor. Successful use of alternative donors, including mismatched family members, could provide a donor for almost all patients with SCD. The use of a reduced-intensity conditioning regimen may decrease late adverse effects. Ten patients with symptomatic SCD underwent CD34+ cell-selected, T-cell–depleted peripheral blood stem cell transplantation from a mismatched family member or unrelated donor. A reduced-intensity conditioning regimen including melphalan, thiotepa, fludarabine, and rabbit anti-thymocyte globulin was used. Patients were screened for a companion study for immune reconstitution that included a donor lymphocyte infusion given 30-42 days after transplant with intravenous methotrexate as graft-versus-host disease (GVHD) prophylaxis. Seven eligible patients were treated on the companion study. Nine of 10 patients are alive with a median follow-up of 49 months (range, 14-60 months). Surviving patients have stable donor hematopoietic engraftment (mean donor chimerism, 99.1% ± 0.7%). There were no sickle cell complications after transplant. Two patients had grade II-IV acute GVHD. One patient had chronic GVHD. Epstein-Barr virus–related posttransplant lymphoproliferative disorder (PTLD) occurred in 3 patients, and 1 patient died as a consequence of treatment of PTLD. Two-year overall survival was 90%, and event-free survival was 80%. A reduced-intensity conditioning regimen followed by CD34+ cell-selected, T-cell–depleted alternative donor peripheral blood stem cell transplantation achieved primary engraftment in all patients with a low incidence of GVHD, although PTLD was problematic. This trial was registered at clinicaltrials.gov as #NCT00968864. PMID:29296761

Diurnal variations of dissolved and colloidal organic carbon and trace metals in a boreal lake during summer bloom.

PubMed

Pokrovsky, O S; Shirokova, L S

2013-02-01

This work describes variation of element concentration in surface water of a subarctic organic-rich lake during the diurnal cycle of photosynthesis. An unusually hot summer 2010 in European part of subarctic Russia produced elevated surface water temperature (28-30 °C) and caused massive cyanobacterial bloom. Diurnal variation of ~40 dissolved macro and trace elements and organic carbon were recorded in the humic Lake Svyatoe in the White Sea drainage basin. Two days continuous measurements with 3 h sampling steps at the surface (0.5 m) allowed tracing cyanobacterial activity via pH and O₂ measurement and revealed constant concentrations (within ±20-30%) of all major elements (Na, Mg, Cl, SO₄, K, Ca), organic and inorganic carbon and most trace elements (Li, B, Sc, Ti, Ni, Cu, Ga, As, Rb, Sr, Y, Zr, Mo, Sb, medium and heavy REEs, Hf, Pb, Th, U). The concentration of Mn demonstrated a factor of 3 decrease during the day following Mn adsorption onto cyanobacterial cells due to ~1 pH unit raise during the photosynthesis and Mn release during the night due to desorption from the cell surface. The role of Mn(II) photo-oxidation by reactive oxygen species could be also pronounced, although its contribution to Mn diurnal variation was much smaller than the adsorption at the cell surfaces. Similar pattern, but with much lesser variations (c.a., 10-20%), was recorded for Ba and Fe. On-site ultrafiltration technique allowed to distinguish between low molecular weight (LMW) complexes (<1 kDa) and high molecular weight (HMW) colloids (1 kDa-0.22 μm) and to assess their diurnal pattern. Colloidal Al and Fe were the highest during the night, when the contribution of HMW allochthonous colloids was maximal. Typical insoluble trivalent and tetravalent elements exhibited constant complexation (>80-90%) with HMW allochthonous organics, independent on the diel photosynthetic cycle. Finally, biologically-relevant metals (Cu, Co, Cr, V, and Ni) demonstrated significant variations of colloidal fractions (from 10 to 60%) not directly related to the photosynthesis. The majority of possible metal nutrients, being strongly associated with organic and organo-mineral colloids do not exhibit any measurable concentration variation during photosynthesis. The two types of element behavior during cyanobacterial bloom in the water column--constant concentration and sinusoidal variations--likely depend on element speciation in solution and their relative affinity to surfaces of aquatic microorganisms and complexation with authochthonous and allochthonous organic matter. Copyright © 2012 Elsevier Ltd. All rights reserved.

Tie-dyed2 Encodes a Callose Synthase That Functions in Vein Development and Affects Symplastic Trafficking within the Phloem of Maize Leaves12[C][W][OA

PubMed Central

Slewinski, Thomas L.; Baker, R. Frank; Stubert, Adam; Braun, David M.

2012-01-01

The tie-dyed2 (tdy2) mutant of maize (Zea mays) displays variegated green and yellow leaves. Intriguingly, the yellow leaf tissues hyperaccumulate starch and sucrose, the soluble sugar transported long distance through the phloem of veins. To determine the molecular basis for Tdy2 function, we cloned the gene and found that Tdy2 encodes a callose synthase. RNA in situ hybridizations revealed that in developing leaves, Tdy2 was most highly expressed in the vascular tissue. Comparative expression analysis with the vascular marker maize PINFORMED1a-yellow fluorescent protein confirmed that Tdy2 was expressed in developing vein tissues. To ascertain whether the defect in tdy2 leaves affected the movement of sucrose into the phloem or its long-distance transport, we performed radiolabeled and fluorescent dye tracer assays. The results showed that tdy2 yellow leaf regions were defective in phloem export but competent in long-distance transport. Furthermore, transmission electron microscopy of tdy2 yellow leaf regions showed incomplete vascular differentiation and implicated a defect in cell-to-cell solute movement between phloem companion cells and sieve elements. The disruption of sucrose movement in the phloem in tdy2 mutants provides evidence that the Tdy2 callose synthase functions in vascular maturation and that the vascular defects result in impaired symplastic trafficking into the phloem translocation stream. PMID:22932757

“You’re dealing with an emotionally charged individual…”: an industry perspective on the challenges posed by medical tourists’ informal caregiver-companions

PubMed Central

2013-01-01

Background Patients engage in medical tourism when they privately obtain a medical care abroad. Previous research shows that many medical tourists travel abroad with friends and family members who provide support and assistance. Meanwhile, very little is known about this important stakeholder group, referred to here as caregiver-companions. In this article we examine the challenges that can be posed by caregiver-companions and the overall practice of informal caregiving in medical tourism from an industry perspective. Specifically, we report on the findings of interviews conducted with international patient coordinators (IPCs) who work at destination facilities. IPCs come into regular contact with caregiver-companions in their professional positions and thus are ideally suited to comment on trends they have observed among this stakeholder group as well as the challenges they can pose to medical tourists, health workers, and facilities. Methods We conducted 20 semi-structured interviews with 21 IPCs from 16 different facilities across nine countries. Topics probed in the interviews included caregiver-companion roles, IPCs’ and others’ interaction with caregiver-companions, and potential health and safety risks posed to medical tourists and caregiver-companions. Thematic analysis of the verbatim transcripts was employed. Results Although most participants encouraged medical tourists to travel with a caregiver-companion, many challenges associated with caregiver-companions were identified. Three themes best characterize the challenges that emerged: (1) caregiver-companions require time, attention and resources; (2) caregiver-companions can disrupt the provision of quality care; and (3) caregiver-companions can be exposed to risks. IPCs pointed out that caregiver-companions may, for example, have a negative impact on the patient through cost of accompaniment or inadequate care provision. Caregiver-companions may also create unanticipated or extra work for IPCs, as additional clients and by ignoring established organizational rules, routines, and expectations. Furthermore, caregiver-companions may be susceptible to stresses and health and safety risks, which would further deteriorate their own abilities to offer the patient quality care. Conclusions Although caregiver-companions can pose challenges to medical tourists, health workers, and medical tourism facilities, they can also assist in enhancing best care and offering meaningful support to medical tourists. If caregiver-companions are open to collaboration with IPCs, and particularly in the form of information sharing, then their experience abroad can be safer and less stressful for themselves and, by extension, for the accompanied patients and facility staff. PMID:23889860

"You're dealing with an emotionally charged individual...": an industry perspective on the challenges posed by medical tourists' informal caregiver-companions.

PubMed

Casey, Victoria; Crooks, Valorie A; Snyder, Jeremy; Turner, Leigh

2013-07-26

Patients engage in medical tourism when they privately obtain a medical care abroad. Previous research shows that many medical tourists travel abroad with friends and family members who provide support and assistance. Meanwhile, very little is known about this important stakeholder group, referred to here as caregiver-companions. In this article we examine the challenges that can be posed by caregiver-companions and the overall practice of informal caregiving in medical tourism from an industry perspective. Specifically, we report on the findings of interviews conducted with international patient coordinators (IPCs) who work at destination facilities. IPCs come into regular contact with caregiver-companions in their professional positions and thus are ideally suited to comment on trends they have observed among this stakeholder group as well as the challenges they can pose to medical tourists, health workers, and facilities. We conducted 20 semi-structured interviews with 21 IPCs from 16 different facilities across nine countries. Topics probed in the interviews included caregiver-companion roles, IPCs' and others' interaction with caregiver-companions, and potential health and safety risks posed to medical tourists and caregiver-companions. Thematic analysis of the verbatim transcripts was employed. Although most participants encouraged medical tourists to travel with a caregiver-companion, many challenges associated with caregiver-companions were identified. Three themes best characterize the challenges that emerged: (1) caregiver-companions require time, attention and resources; (2) caregiver-companions can disrupt the provision of quality care; and (3) caregiver-companions can be exposed to risks. IPCs pointed out that caregiver-companions may, for example, have a negative impact on the patient through cost of accompaniment or inadequate care provision. Caregiver-companions may also create unanticipated or extra work for IPCs, as additional clients and by ignoring established organizational rules, routines, and expectations. Furthermore, caregiver-companions may be susceptible to stresses and health and safety risks, which would further deteriorate their own abilities to offer the patient quality care. Although caregiver-companions can pose challenges to medical tourists, health workers, and medical tourism facilities, they can also assist in enhancing best care and offering meaningful support to medical tourists. If caregiver-companions are open to collaboration with IPCs, and particularly in the form of information sharing, then their experience abroad can be safer and less stressful for themselves and, by extension, for the accompanied patients and facility staff.

Synthesis, characterization, DFT calculations and biological studies of Mn(II), Fe(II), Co(II) and Cd(II) complexes based on a tetradentate ONNO donor Schiff base ligand

NASA Astrophysics Data System (ADS)

Abdel-Rahman, Laila H.; Ismail, Nabawia M.; Ismael, Mohamed; Abu-Dief, Ahmed M.; Ahmed, Ebtehal Abdel-Hameed

2017-04-01

This study highlights synthesis and characterization of a tetradentate ONNO Schiff base ligand namely (1, 1‧- (pyridine-2, 3-dimethyliminomethyl) naphthalene-2, 2‧-diol) and hereafter denotes as "HNDAP″ and selected metal complexes including Mn(II), Fe(II), Co(II) and Cd(II) as a central metal. HNDAP was synthesized from 1:2 M ratio condensation of 2, 3-diaminopyridine and 2- hydroxy-1-naphthaldhyde, respectively. The stoichiometric ratios of the prepared complexes were estimated using complementary techniques such as; elemental analyses (-C, H, N), FT-IR, magnetic measurements and molar conductivity. Furthermore, their physicochemical studies were carried out using thermal TGA, DTA and kinetic-thermodynamic studies along with DFT calculations. The results of elemental analyses showed that these complexes are present in a 1:1 metal-to- ligand molar ratio. Moreover, the magnetic susceptibilities values at room temperature revealed that Mn(II), Fe(II) and Co(II) complexes are paramagnetic in nature and have an octahedral (Oh) geometry. In contrast, Cd(II) is diamagnetic and stabilizes in square planar sites. The molar conductivity measurements indicated that all complexes are nonelectrolytes in dimethyl formamide. Spectral data suggested that the ligand is as tetradentate and coordinated with Co(II) ion through two phenolic OH and two azomethine nitrogen. However, for Mn(II), Fe(II) and Cd(II) complexes, the coordination occurred through two phenolic oxygen and two azomethine nitrogen with deprotonation of OH groups. The proposed chemical structures have been validated by quantum mechanics calculations. Antimicrobial activities of both the HNDAP Schiff base ligand and its metal complexes were tested against strains of Gram (-ve) E. coli and Gram (+ve) B. subtilis and S. aureus bacteria and C. albicans, A. flavus and T. rubrum fungi. All the prepared compounds showed good results of inhibition against the selected pathogenic microorganisms. The investigated HNDAP Schiff base complexes showed higher activity and stability than their corresponding HNDAP Schiff base ligand and the highest activity observed for Cd(II) complex. Moreover, the prepared Schiff base ligand and its Mn(II) and Co(II) complexes have been evaluated for their anticancer activities against two cancer cell lines namely; colon carcinoma cells (HCT-116 cell line) and hepatocellular carcinoma (Hep-G2) cell lines The interaction of Mn(II) and Co(II) complexes with calf thymus DNA (CT-DNA) was studied by absorption spectroscopic technique and viscosity measurements. Both complexes showed a successful interaction with CT-DNA via intercalation mode.

Bacterial Cell Surface Adsorption of Rare Earth Elements

NASA Astrophysics Data System (ADS)

Jiao, Y.; Park, D.; Reed, D.; Fujita, Y.; Yung, M.; Anderko, A.; Eslamimanesh, A.

2015-12-01

Rare earth elements (REE) play a critical role in many emerging clean energy technologies, including high-power magnets, wind turbines, solar panels, hybrid/electric vehicle batteries and lamp phosphors. In order to sustain demand for such technologies given current domestic REE shortages, there is a need to develop new approaches for ore processing/refining and recycling of REE-containing materials. To this end, we have developed a microbially-mediated bioadsorption strategy with application towards enrichment of REE from complex mixtures. Specifically, the bacterium Caulobacter crescentus was genetically engineered to display lanthanide binding tags (LBTs), short peptides that possess high affinity and specificity for rare earth elements, on its cell surface S-layer protein. Under optimal conditions, LBT-displayed cells adsorbed greater than 5-fold more REE than control cells lacking LBTs. Competition binding experiments with a selection of REEs demonstrated that our engineered cells could facilitate separation of light- from heavy- REE. Importantly, binding of REE onto our engineered strains was much more favorable compared to non-REE metals. Finally, REE bound to the cell surface could be stripped off using citrate, providing an effective and non-toxic REE recovery method. Together, this data highlights the potential of our approach for selective REE enrichment from REE containing mixtures.

[Participation of the piRNA pathway in recruiting a component of RNA polymerase I transcription initiation complex to germline cell nucleoli].

PubMed

Fefelova, E A; Stolyarenko, A D; Yakushev, E Y; Gvozdev, V A; Klenov, M S

2017-01-01

Proteins of the Piwi family and short Piwi-interacting RNAs (piRNAs) ensure the protection of the genome from transposable elements. We have previously shown that nuclear Piwi protein tends to concentrate in the nucleoli of the cells of Drosophila melanogaster ovaries. It could be hypothesized that the function of Piwi in the nucleolus is associated with the repression of R1 and R2 retrotransposons inserted into the rDNA cluster. Here, we show that Piwi participates in recruiting Udd protein to nucleoli. Udd is a component of the conserved Selectivity Factor I-like (SL1-like) complex, which is required for transcription initiation by RNA polymerase I. We found that Udd localization depends on Piwi in germline cells, but not in somatic cells of the ovaries. In contrast, knockdowns of the SL1-like components (Udd or TAF1b) do not disrupt Piwi localization. We also observed that the absence of Udd or TAF1b in germline cells, as well as the impairment of Piwi nuclear localization lead to the accumulation of late stage egg chambers in the ovaries, which could be explained by reduced rRNA transcription. These results allow us to propose for the first time a role for Piwi in the nucleolus that is not directly associated with transposable element repression.

Focal plane based wavefront sensing with random DM probes

NASA Astrophysics Data System (ADS)

Pluzhnik, Eugene; Sirbu, Dan; Belikov, Ruslan; Bendek, Eduardo; Dudinov, Vladimir N.

2017-09-01

An internal coronagraph with an adaptive optical system for wavefront control is being considered for direct imaging of exoplanets with upcoming space missions and concepts, including WFIRST, HabEx, LUVOIR, EXCEDE and ACESat. The main technical challenge associated with direct imaging of exoplanets is to control of both diffracted and scattered light from the star so that even a dim planetary companion can be imaged. For a deformable mirror (DM) to create a dark hole with 10-10 contrast in the image plane, wavefront errors must be accurately measured on the science focal plane detector to ensure a common optical path. We present here a method that uses a set of random phase probes applied to the DM to obtain a high accuracy wavefront estimate even for a dynamically changing optical system. The presented numerical simulations and experimental results show low noise sensitivity, high reliability, and robustness of the proposed approach. The method does not use any additional optics or complex calibration procedures and can be used during the calibration stage of any direct imaging mission. It can also be used in any optical experiment that uses a DM as an active optical element in the layout.

Transcriptional activation of transforming growth factor alpha by estradiol: requirement for both a GC-rich site and an estrogen response element half-site.

PubMed

Vyhlidal, C; Samudio, I; Kladde, M P; Safe, S

2000-06-01

17beta-Estradiol (E2) induces transforming growth factor alpha (TGFalpha) gene expression in MCF-7 cells and previous studies have identified a 53 bp (-252 to -200) sequence containing two imperfect estrogen responsive elements (EREs) that contribute to E2 responsiveness. Deletion analysis of the TGFalpha gene promoter in this study identified a second upstream region of the promoter (-623 to -549) that is also E2 responsive. This sequence contains three GC-rich sites and an imperfect ERE half-site, and the specific cis-elements and trans-acting factors were determined by promoter analysis in transient transfection experiments, gel mobility shift assays and in vitro DNA footprinting. The results are consistent with an estrogen receptor alpha (ERalpha)/Sp1 complex interacting with an Sp1(N)(30) ERE half-site ((1/2)) motif in which both ERalpha and Sp1 bind promoter DNA. The ER/Sp1-DNA complex is formed using nuclear extracts from MCF-7 cells but not with recombinant human ERalpha or Sp1 proteins, suggesting that other nuclear factor(s) are required for complex stabilization. The E2-responsive Sp1(N)(x)ERE(1/2) motif identified in the TGFalpha gene promoter has also been characterized in the cathepsin D and heat shock protein 27 gene promoters; however, in the latter two promoters the numbers of intervening nucleotides are 23 and 10 respectively.

Design, synthesis, DNA-binding affinity, cytotoxicity, apoptosis, and cell cycle arrest of Ru(II) polypyridyl complexes.

PubMed

Venkat Reddy, Putta; Reddy, Mallepally Rajender; Avudoddi, Srishailam; Praveen Kumar, Yata; Nagamani, Chintakuntla; Deepika, Nancherla; Nagasuryaprasad, K; Singh, Surya Satyanarayana; Satyanarayana, Sirasani

2015-09-15

A novel polypyridyl ligand CNPFIP (CNPFIP=2-(5(4-chloro-2-nitrophenyl)furan-2-yl)-1H-imidazo[4,5f][1,10]phenanthroline) and its mononuclear Ru(II) polypyridyl complexes of [Ru(phen)2CNPFIP](2+)(1) (phen=1,10-phenanthroline), [Ru(bpy)2CNPFIP](2+)(2) (bpy=2,2'-bipyridine), and [Ru(dmb)2CNPFIP](2+)(3) (dmb=4,4'-dimethyl-2,2'-bipyridine) have been synthesized successfully and characterized thoroughly by elemental analysis, UV/Vis, IR, NMR, and ESI-MS. The interaction of the Ru(II) complexes with calf thymus DNA (CT-DNA) was investigated by absorption titration, fluorescence, viscosity measurements. The experimental results suggest that three complexes bind to CT-DNA through an intercalative mode and the DNA-binding affinity of complex 1 is greater than that of complexes 2 and 3. The photocleavage of plasmid pBR322 DNA by ruthenium complexes 1, 2, and 3 was investigated. We have also tested three complexes for their antimicrobial activity against Escherichia coli (Gram-negative) and Staphylococcus aureus (Gram-positive) bacteria. The in vitro cytotoxicity of these complexes was evaluated by MTT assay, and complex 1 shows higher cytotoxicity than 2 and 3 on HeLa cells. The induced apoptosis and cell cycle arrest of HeLa cells were investigated by flow cytometry for 24h. The molecular docking of ruthenium complexes 1, 2, and 3 with the active site pocket residues of human DNA TOP1 was performed using LibDock. Copyright © 2015 Elsevier Inc. All rights reserved.

Factors affecting the quality of hospital hotel services from the patients and their companions' point of view: A national study in Iran.

PubMed

Shirzadi, Seyed Majid; Raeissi, Pouran; Nasiripour, Amir Ashkan; Tabibi, Seyed Jamaleddin

2016-01-01

The hospitality design of a hospital is a complex process that depends on careful planning, systematic thinking, and consideration of various factors. This study aimed to determine the viewpoints of patients and their relatives on factors affecting hospital hotel services in Iran in 2015. The results of this study can be used to design a suitable model for the assessment and improvement of hospitality service quality. In this cross-sectional descriptive study, 10 hospitals of Iran were included. The subjects of the study included 480 patients and their companions from different internal and surgical wards. Simple random sampling method was performed at the hospitals, where patients were selected through stratified sampling based on hospital wards, and in each ward, through systematic sampling based on the bed numbers. A researcher-made questionnaire was used as the study tool which was developed through reviewing the literature and opinions of experts. Its internal reliability was determined based on Cronbach's alpha coefficient (α =0.85). In reviewing the eleven aspects of hospital hotel services regarding the patients' and their companions' viewpoint, services related to all aspects, whether human, economic, operational, personnel identification, safety, health care services, physical, clinical welfare, cultural, patient guidance, or public welfare services, received mean scores of higher than three (out of five). The present study showed that in the patients' and their companions' viewpoint, factors affecting hospital hotel services in the country are very important. The tool used in this study can be a criterion for assessing the status of the hotel services of the country's major hospitals, so accordingly, the assessment and improvement of the existing conditions can be possible.

Effects of reactive Mn(III)-oxalate complexes on structurally intact plant cell walls

NASA Astrophysics Data System (ADS)

Summering, J. A.; Keiluweit, M.; Goni, M. A.; Nico, P. S.; Kleber, M.

2011-12-01

Lignin components in the in plant litter are commonly assumed to have longer residence times in soil than many other compounds, which are supposedly, more easily degradable. The supposed resistance of lignin compounds to decomposition is generally attributed to the complex chain of biochemical steps required to create footholds in the non-porous structure of ligno-cellulose in cell walls. Interestingly, Mn(III) complexes have shown the ability to degrade ligno-cellulose. Mn(III) chelated by ligands such as oxalate are soluble oxidizers with a high affinity for lignin structures. Here we determined (i) the formation and decay kinetics of the Mn(III)-oxalate complexes in aqueous solution and (ii) the effects that these complexes have on intact ligno-cellulose. UV/vis spectroscopy and iodometric titrations confirmed the transient nature of Mn(III)-oxalate complexes with decay rates being in the order of hours. Zinnia elegans tracheary elements - a model ligno-cellulose substrate - were treated with Mn(III)-oxalate complexes in a newly developed flow-through reactor. Soluble decomposition products released during the treatment were analyzed by GC/MS and the degree of cell integrity was measured by cell counts, pre- and post-treatment counts indicate a decrease in intact Zinnia elegans as a result of Mn(III)-treatment. GC/MS results showed the release of a multitude of solubilized lignin breakdown products from plant cell walls. We conclude that Mn(III)-oxalate complexes have the ability to lyse intact plant cells and solubilize lignin. Lignin decomposition may thus be seen as resource dependent, with Mn(III) a powerful resource that should be abundant in terrestrial characterized by frequent redox fluctuations.

The Senior Companion Program Plus: A culturally tailored psychoeducational training program (innovative practice).

PubMed

Fields, Noelle L; Xu, Ling; Richardson, Virginia E; Parekh, Rupal; Ivey, Dorothea; Feinhals, Gretchen; Calhoun, Melanie

2016-01-01

A purposive sample of African American Senior Companions ( N = 23) participated in a 5-day, 20-hour psychoeducational training designed to address the unique cultural needs of African American dementia caregivers. Previous studies have not utilized lay caregiver volunteers such as Senior Companions in dementia research in the United States. Pre- and post-tests were administered to determine whether African American Senior Companions increased their knowledge of Alzheimer's disease after participating in the Senior Companion Program Plus. Results from both the quantitative and qualitative data suggest that participants improved their understanding of Alzheimer's disease. Findings from the Senior Companion Program Plus pilot warrant further study for its potential as cost effective, culturally tailored training for Senior Companions who serve persons with dementia and their family caregivers.

Revisiting the B-cell compartment in mouse and humans: more than one B-cell subset exists in the marginal zone and beyond.

PubMed

Garraud, Olivier; Borhis, Gwenoline; Badr, Gamal; Degrelle, Séverine; Pozzetto, Bruno; Cognasse, Fabrice; Richard, Yolande

2012-11-29

The immunological roles of B-cells are being revealed as increasingly complex by functions that are largely beyond their commitment to differentiate into plasma cells and produce antibodies, the key molecular protagonists of innate immunity, and also by their compartmentalisation, a more recently acknowledged property of this immune cell category. For decades, B-cells have been recognised by their expression of an immunoglobulin that serves the function of an antigen receptor, which mediates intracellular signalling assisted by companion molecules. As such, B-cells were considered simple in their functioning compared to the other major type of immune cell, the T-lymphocytes, which comprise conventional T-lymphocyte subsets with seminal roles in homeostasis and pathology, and non-conventional T-lymphocyte subsets for which increasing knowledge is accumulating. Since the discovery that the B-cell family included two distinct categories - the non-conventional, or extrafollicular, B1 cells, that have mainly been characterised in the mouse; and the conventional, or lymph node type, B2 cells - plus the detailed description of the main B-cell regulator, FcγRIIb, and the function of CD40(+) antigen presenting cells as committed/memory B-cells, progress in B-cell physiology has been slower than in other areas of immunology. Cellular and molecular tools have enabled the revival of innate immunity by allowing almost all aspects of cellular immunology to be re-visited. As such, B-cells were found to express "Pathogen Recognition Receptors" such as TLRs, and use them in concert with B-cell signalling during innate and adaptive immunity. An era of B-cell phenotypic and functional analysis thus began that encompassed the study of B-cell microanatomy principally in the lymph nodes, spleen and mucosae. The novel discovery of the differential localisation of B-cells with distinct phenotypes and functions revealed the compartmentalisation of B-cells. This review thus aims to describe novel findings regarding the B-cell compartments found in the mouse as a model organism, and in human physiology and pathology. It must be emphasised that some differences are noticeable between the mouse and human systems, thus increasing the complexity of B-cell compartmentalisation. Special attention will be given to the (lymph node and spleen) marginal zones, which represent major crossroads for B-cell types and functions and a challenge for understanding better the role of B-cell specificities in innate and adaptive immunology.

Human common acute lymphoblastic leukemia-derived cell lines are competent to recombine their T-cell receptor delta/alpha regions along a hierarchically ordered pathway.

PubMed

Hansen-Hagge, T E; Yokota, S; Reuter, H J; Schwarz, K; Bartram, C R

1992-11-01

Rearrangements of the T-cell receptor (TCR) delta locus are observed in the majority of human B-cell precursor acute lymphoblastic leukemias (ALL) with a striking predominance of V delta 2(D)D delta 3 recombinations in common ALL (cALL) patients. Recently, we and others showed that almost 20% of cALL cases are characterized by further recombination of V delta 2(D)D delta 3 segments to J alpha elements, thereby deleting the TCR delta locus in analogy to the delta Rec/psi J alpha pathway in differentiating alpha/beta-positive T cells. We report here that two human cALL-derived cell lines, REH and Nalm-6, are competent to recombine the TCR delta/alpha locus under standard tissue culture conditions. Analysis of different REH subclones obtained by limiting dilution of the initial culture showed a biased recombination of V delta 2D delta 3 to distinct J alpha elements. During prolonged tissue culture, a subclone acquired growth advantage and displaced parental cells as well as other subclones. Frequently, the DJ junctions of REH subclones contained extended stretches of palindromic sequences derived from modified D delta 3 coding elements. The other cell line, Nalm-6, started the TCR delta/alpha recombination with an unusual signal joint of a cryptic recombinase signal sequence (RSS) upstream of D delta 3 to the 3' RSS of D delta 3. The RSS dimer was subsequently rearranged in all investigated subclones to an identical J alpha element. Both cell lines might become valuable tools to unravel the complex regulation of TCR delta/alpha recombination pathways in malignant and normal lymphopoiesis.

The search for the elusive companion of EG andromedae

NASA Technical Reports Server (NTRS)

Pesce, Joseph E.; Stencel, Robert E.; Oliversen, Nancy A.

1987-01-01

Observations are reported at opposite quadratures of the interacting symbiotic binary EG And (HD-4174, Period = 470 d). After correcting for absolute motion at the system, it appears, surprisingly, that many of the nebular lines arise from material that moves with the red giant star. This fact is used to interpret the observed complex line profiles of C IV and He II in the object.

Synthetic Biomimetic Fluorophores for Micro/Nanosensor

DTIC Science & Technology

2006-11-01

as a companion protein to aequorin, the famous chemiluminescent protein from the brightly luminescent Aequorea jellyfish , with glowing points...peaked near 470 nm, which was close to one of the excitation peaks of GFP. Aequorin, isolated from the jellyfish Aequorea victoria, is a complex of...partially homologous to green fluorescent protein (GFP) (Matz et al. 1999, Dove et al. 2000), first found in the luminescent jellyfish Aequorea and used

Hot-Fire Test Results of an Oxygen/RP-2 Multi-Element Oxidizer-Rich Staged-Combustion Integrated Test Article

NASA Technical Reports Server (NTRS)

Hulka, J. R.; Protz, C. S.; Garcia, C. P.; Casiano, M. J.; Parton, J. A.

2016-01-01

As part of the Combustion Stability Tool Development project funded by the Air Force Space and Missile Systems Center, the NASA Marshall Space Flight Center was contracted to assemble and hot-fire test a multi-element integrated test article demonstrating combustion characteristics of an oxygen/hydrocarbon propellant oxidizer-rich staged-combustion engine thrust chamber. Such a test article simulates flow through the main injectors of oxygen/kerosene oxidizer-rich staged combustion engines such as the Russian RD-180 or NK-33 engines, or future U.S.-built engine systems such as the Aerojet-Rocketdyne AR-1 engine or the Hydrocarbon Boost program demonstration engine. For the thrust chamber assembly of the test article, several configurations of new main injectors, using relatively conventional gas-centered swirl coaxial injector elements, were designed and fabricated. The design and fabrication of these main injectors are described in a companion paper at this JANNAF meeting. New ablative combustion chambers were fabricated based on hardware previously used at NASA for testing at similar size and pressure. An existing oxygen/RP-1 oxidizer-rich subscale preburner injector from a previous NASA-funded program, along with existing and new inter-connecting hot gas duct hardware, were used to supply the oxidizer-rich combustion products to the oxidizer circuit of the main injector of the thrust chamber. Results from independent hot-fire tests of the preburner injector in a combustion chamber with a sonic throat are described in companion papers at this JANNAF conference. The resulting integrated test article - which includes the preburner, inter-connecting hot gas duct, main injector, and ablative combustion chamber - was assembled at Test Stand 116 at the East Test Area of the NASA Marshall Space Flight Center. The test article was well instrumented with static and dynamic pressure, temperature, and acceleration sensors to allow the collected data to be used for combustion analysis model development. Hot-fire testing was conducted with main combustion chamber pressures ranging from 1400 to 2100 psia, and main combustion chamber mixture ratios ranging from 2.4 to 2.9. Different levels of fuel film cooling injected from the injector face were examined ranging from none to about 12% of the total fuel flow. This paper presents the hot-fire test results of the integrated test article. Combustion performance, stability, thermal, and compatibility characteristics of both the preburner and the thrust chamber are described. Another companion paper at this JANNAF meeting includes additional and more detailed test data regarding the combustion dynamics and stability characteristics.

A new method to real-normalize measured complex modes

NASA Technical Reports Server (NTRS)

Wei, Max L.; Allemang, Randall J.; Zhang, Qiang; Brown, David L.

1987-01-01

A time domain subspace iteration technique is presented to compute a set of normal modes from the measured complex modes. By using the proposed method, a large number of physical coordinates are reduced to a smaller number of model or principal coordinates. Subspace free decay time responses are computed using properly scaled complex modal vectors. Companion matrix for the general case of nonproportional damping is then derived in the selected vector subspace. Subspace normal modes are obtained through eigenvalue solution of the (M sub N) sup -1 (K sub N) matrix and transformed back to the physical coordinates to get a set of normal modes. A numerical example is presented to demonstrate the outlined theory.

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 model form complexity are challenging but are essential for successful modeling of large-scale systems in reasonable time. Currently there is to this end no established methodology from computational sciences. PMID:16093514

Telescoping Mechanics: A New Paradigm for Composite Behavior Simulation

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Murthy, P. L. N.; Gotsis, P. K.; Mital. S. K.

2004-01-01

This report reviews the application of telescoping mechanics to composites using recursive laminate theory. The elemental scale is the fiber-matrix slice, the behavior of which propagates to laminate. The results from using applications for typical, hybrid, and smart composites and composite-enhanced reinforced concrete structures illustrate the versatility and generality of telescoping scale mechanics. Comparisons with approximate, single-cell, and two- and three-dimensional finite-element methods demonstrate the accuracy and computational effectiveness of telescoping scale mechanics for predicting complex composite behavior.

The CALLISTO Project: A Summary.

PubMed

Day, M J

2016-07-01

The European Union (EU) Framework 7-funded project entitled CALLISTO (Companion Animal multisectoriaL interprofessionaL and interdisciplinary Strategic Think tank On zoonoses) ran between 2012 and 2014 and investigated zoonotic infectious diseases transmitted between companion animals and man and food producing animals. There are large numbers of companion animals throughout Europe and these animals, of varied species, play an integral role in human society, providing very real human health and welfare benefits. There is, however, some risk that close human contact with companion animals may lead to the transmission of zoonotic infectious diseases of numerous different types. Companion animals may also be a source of some infections transmitted to farmed livestock. This risk must be communicated to the pet owning public in a balanced fashion by veterinary and human healthcare professionals, the pet industry and governments. The risk may be somewhat ameliorated if the owners of companion animals subscribe to the principles of responsible pet ownership. Nevertheless, there are further policy and research actions that could be implemented by the EU and/or national governments to further reduce the risks associated with the close integration of companion animals into human society. These include the development of systems for identifying and registering the most common companion animal species and establishing surveillance programmes that capture data on zoonoses that occur in these animals. Closer attention should be paid to the health status of animals entering or re-entering the EU from third countries and the welfare surrounding companion animal cross-border movement. Data collection and pathogen assessment in the less studied exotic companion animals being kept is also needed to better understand risks. Disease and disease vector spread within Europe should be monitored and solutions found to limit such spread. The emergence of antimicrobial resistance in companion animals should be monitored. Controls should be placed on the use of human critically important antibiotics in companion animal species, but new approaches to companion animal antimicrobial therapy must be developed in parallel. Copyright © 2015 Elsevier Ltd. All rights reserved.

A companion on the planet/brown dwarf mass boundary on a wide orbit discovered by gravitational microlensing

NASA Astrophysics Data System (ADS)

Poleski, R.; Udalski, A.; Bond, I. A.; Beaulieu, J. P.; Clanton, C.; Gaudi, S.; Szymański, M. K.; Soszyński, I.; Pietrukowicz, P.; Kozłowski, Szymon; Skowron, J.; Wyrzykowski, Ł.; Ulaczyk, K.; Bennett, D. P.; Sumi, T.; Suzuki, D.; Rattenbury, N. J.; Koshimoto, N.; Abe, F.; Asakura, Y.; Barry, R. K.; Bhattacharya, A.; Donachie, M.; Evans, P.; Fukui, A.; Hirao, Y.; Itow, Y.; Li, M. C. A.; Ling, C. H.; Masuda, K.; Matsubara, Y.; Muraki, Y.; Nagakane, M.; Ohnishi, K.; Ranc, C.; Saito, To.; Sharan, A.; Sullivan, D. J.; Tristram, P. J.; Yamada, T.; Yamada, T.; Yonehara, A.; Batista, V.; Marquette, J. B.

2017-08-01

We present the discovery of a substellar companion to the primary host lens in the microlensing event MOA-2012-BLG-006. The companion-to-host mass ratio is 0.016, corresponding to a companion mass of ≈8 MJup(M∗/ 0.5 M⊙). Thus, the companion is either a high-mass giant planet or a low-mass brown dwarf, depending on the mass of the primary M∗. The companion signal was separated from the peak of the primary event by a time that was as much as four times longer than the event timescale. We therefore infer a relatively large projected separation of the companion from its host of ≈10 au(M∗/ 0.5 M⊙)1 / 2 for a wide range (3-7 kpc) of host star distances from the Earth. We also challenge a previous claim of a planetary companion to the lens star in microlensing event OGLE-2002-BLG-045.

Arabidopsis Nitrate Transporter NRT1.9 Is Important in Phloem Nitrate Transport[W][OA

PubMed Central

Wang, Ya-Yun; Tsay, Yi-Fang

2011-01-01

This study of the Arabidopsis thaliana nitrate transporter NRT1.9 reveals an important function for a NRT1 family member in phloem nitrate transport. Functional analysis in Xenopus laevis oocytes showed that NRT1.9 is a low-affinity nitrate transporter. Green fluorescent protein and β-glucuronidase reporter analyses indicated that NRT1.9 is a plasma membrane transporter expressed in the companion cells of root phloem. In nrt1.9 mutants, nitrate content in root phloem exudates was decreased, and downward nitrate transport was reduced, suggesting that NRT1.9 may facilitate loading of nitrate into the root phloem and enhance downward nitrate transport in roots. Under high nitrate conditions, the nrt1.9 mutant showed enhanced root-to-shoot nitrate transport and plant growth. We conclude that phloem nitrate transport is facilitated by expression of NRT1.9 in root companion cells. In addition, enhanced root-to-shoot xylem transport of nitrate in nrt1.9 mutants points to a negative correlation between xylem and phloem nitrate transport. PMID:21571952

A Kinetic Model for Calcium Dynamics in RAW 264.7 Cells: 2. Knockdown Response and Long-Term Response

PubMed Central

Maurya, Mano Ram; Subramaniam, Shankar

2007-01-01

This article addresses how quantitative models such as the one proposed in the companion article can be used to study cellular network perturbations such as knockdowns and pharmacological perturbations in a predictive manner. Using the kinetic model for cytosolic calcium dynamics in RAW 264.7 cells developed in the companion article, the calcium response to complement 5a (C5a) for the knockdown of seven proteins (C5a receptor; G-β-2; G-α,i-2,3; regulator of G-protein signaling-10; G-protein coupled receptor kinase-2; phospholipase C β-3; arrestin) is predicted and validated against the data from the Alliance for Cellular Signaling. The knockdown responses provide insights into how altered expressions of important proteins in disease states result in intermediate measurable phenotypes. Long-term response and long-term dose response have also been predicted, providing insights into how the receptor desensitization, internalization, and recycle result in tolerance. Sensitivity analysis of long-term response shows that the mechanisms and parameters in the receptor recycle path are important for long-term calcium dynamics. PMID:17483189

Scion on a Stock Producing siRNAs of Potato Spindle Tuber Viroid (PSTVd) Attenuates Accumulation of the Viroid

PubMed Central

Kasai, Atsushi; Sano, Teruo; Harada, Takeo

2013-01-01

Plants can attenuate the replication of plant viruses and viroids by RNA silencing induced by virus and viroid infection. In higher plants, silencing signals such as small interfering RNAs (siRNAs) produced by RNA silencing can be transported systemically through phloem, so it is anticipated that antiviral siRNA signals produced in a stock would have the potential to attenuate propagation of viruses or viroids in the scion. To test whether this is indeed the case, we prepared transgenic tobacco (Nicotiana benthamiana) expressing a hairpin RNA (hpRNA) of Potato spindle tuber viroid (PSTVd) in companion cells by using a strong companion cell-specific promoter. A grafting experiment of the wild type tobacco scion on the top of the transgenic tobacco stock revealed that accumulation of PSTVd challenge-inoculated into the scion was apparently attenuated compared to the control grafted plants. These results indicate that genetically modified rootstock expressing viroid-specific siRNAs can attenuate viroid accumulation in a non-genetically modified scion grafted on the stock. PMID:23469061

Transitions from mono- to co- to tri-culture uniquely affect gene expression in breast cancer, stromal, and immune compartments

PubMed Central

Weinberger, Emma M.; Regehr, Keil J.; Berry, Scott M.; Beebe, David J.; Alarid, Elaine T.

2016-01-01

Heterotypic interactions in cancer microenvironments play important roles in disease initiation, progression, and spread. Co-culture is the predominant approach used in dissecting paracrine interactions between tumor and stromal cells, but functional results from simple co-cultures frequently fail to correlate to in vivo conditions. Though complex heterotypic in vitro models have improved functional relevance, there is little systematic knowledge of how multi-culture parameters influence this recapitulation. We therefore have employed a more iterative approach to investigate the influence of increasing model complexity; increased heterotypic complexity specifically. Here we describe how the compartmentalized and microscale elements of our multi-culture device allowed us to obtain gene expression data from one cell type at a time in a heterotypic culture where cells communicated through paracrine interactions. With our device we generated a large dataset comprised of cell type specific gene-expression patterns for cultures of increasing complexity (three cell types in mono-, co-, or tri-culture) not readily accessible in other systems. Principal component analysis indicated that gene expression was changed in co-culture but was often more strongly altered in tri-culture as compared to mono-culture. Our analysis revealed that cell type identity and the complexity around it (mono-, co-, or tri-culture) influence gene regulation. We also observed evidence of complementary regulation between cell types in the same heterotypic culture. Here we demonstrate the utility of our platform in providing insight into how tumor and stromal cells respond to microenvironments of varying complexities highlighting the expanding importance of heterotypic cultures that go beyond conventional co-culture. PMID:27432323

Synthesis, characterization and anticancer studies of Ni(II), Pd(II) and Pt(II) complexes with Schiff base derived from N-methylhydrazinecarbothioamide and 2-hydroxy-5-methoxy-3-nitrobenzaldehyde

NASA Astrophysics Data System (ADS)

Arafath, Md. Azharul; Adam, Farook; Razali, Mohd. R.; Ahmed Hassan, Loiy E.; Ahamed, Mohamed B. Khadeer; Majid, Amin Malik S. A.

2017-02-01

A carbothioamide NSO tridentate Schiff base ligand (HL) and its square planar complexes Na[NiLOAc], Na[PdLOAc] and [PtLdmso] have been synthesized and characterized on the basis of melting point, elemental analysis, FT-IR, 1H NMR, 13C NMR, UV-Vis spectra. The structure of HL was elucidated with X-ray diffraction analysis. In the present study, the synthesized compounds were evaluated for their anticancer properties against three human cancer cell lines breast cancer (MCF-7), cervical (Hela), and colon (HCT-116). In addition, the cytotoxicity of the synthesized compounds was tested on a normal human cell line (human endothelial cell line EA.hy926). Among the tested compounds, the complex [NiLOAc] excelled in halting proliferation of the cervical and colon cancer cells with median inhibitory concentration (IC50) values of 28.33 and 34.4 μM, respectively. The complex, [PdLOAc] demonstrated selective cytotoxicity against breast cancer line MCF-7 with IC50 = 47.5 μM, while HL showed inhibitory effect against colon cancer cell line (HCT-116) with IC50 = 55.66 μM. The complex, [PtLdmso] showed mild activity against breast cancer (MCF-7) and cervical cancer (Hela) cells with IC50 = 64.44 and 68.3 μM, respectively, whereas, it displayed insignificant cytotoxicity against human endothelial cells (EA.hy926) with IC50 > 200 μM. Cancer cells treated with [NiLOAc] showed apoptotic features such as membrane blebbing and DNA condensation. Thus, the findings of the present study demonstrated that the series of metal complexes of HL could form the new lead for development of cancer chemotherapies to treat human cervical, breast and colon malignancies.

Companion Plants for Aphid Pest Management

PubMed Central

Ben-Issa, Refka; Gomez, Laurent; Gautier, Hélène

2017-01-01

A potential strategy for controlling pests is through the use of “companion plants” within a crop system. This strategy has been used in several trials to fight against a major crop insect pest: the aphid. We reviewed the literature to highlight the major mechanisms by which a companion plant may act. Trials carried out under laboratory or field conditions revealed that companion plants operate through several mechanisms. A companion plant may be associated with a target crop for various reasons. Firstly, it can attract aphids and draw them away from their host plants. Secondly, it can alter the recognition of the host plant. This effect is mostly attributed to companion plant volatiles since they disturb the aphid host plant location, and additionally they may react chemically and physiologically with the host plant, making it an unsuitable host for aphids. Thirdly, it can attract natural enemies by providing shelter and food resources. In this review, the feasibility of using companion plants is discussed. We conclude that many factors need to be taken into account for a successful companion plant strategy. For the best long-term results, companion plant strategies have to be combined with other alternative approaches against aphids. PMID:29053585

A U-Rich Element in the 5′ Untranslated Region Is Necessary for the Translation of p27 mRNA

PubMed Central

Millard, S. Sean; Vidal, Anxo; Markus, Maurice; Koff, Andrew

2000-01-01

Increased translation of p27 mRNA correlates with withdrawal of cells from the cell cycle. This raised the possibility that antimitogenic signals might mediate their effects on p27 expression by altering complexes that formed on p27 mRNA, regulating its translation. In this report, we identify a U-rich sequence in the 5′ untranslated region (5′UTR) of p27 mRNA that is necessary for efficient translation in proliferating and nonproliferating cells. We show that a number of factors bind to the 5′UTR in vitro in a manner dependent on the U-rich element, and their availability in the cytosol is controlled in a growth- and cell cycle-dependent fashion. One of these factors is HuR, a protein previously implicated in mRNA stability, transport, and translation. Another is hnRNP C1 and C2, proteins implicated in mRNA processing and the translation of a specific subset of mRNAs expressed in differentiated cells. In lovastatin-treated MDA468 cells, the mobility of the associated hnRNP C1 and C2 proteins changed, and this correlated with increased p27 expression. Together, these data suggest that the U-rich dependent RNP complex on the 5′UTR may regulate the translation of p27 mRNA and may be a target of antimitogenic signals. PMID:10913178

Synthesis, crystal structure and biological activity of the Schiff base organotin(IV) complexes based on salicylaldehyde-o-aminophenol

NASA Astrophysics Data System (ADS)

Tan, Yu-Xing; Zhang, Zhi-Jian; Liu, Yang; Yu, Jiang-Xi; Zhu, Xiao-Ming; Kuang, Dai-Zhi; Jiang, Wu-Jiu

2017-12-01

Schiff base organotin(IV) complexes C1 ∼ C5b have been synthesized via the reaction of the substituted salicylaldehyde-o-aminophenol Schiff base ligands (L1 ∼ L3) with the dibenzyltin dichloride, n-butyltin trichloride or dibutyltin oxide, respectively. The complexes have been characterized by IR, UV-Vis, 1H NMR, 13C NMR spectra, elemental analysis and the crystal structures have been determined by X-ray diffraction. The anticancer activity of the Schiff base ligand and complexes C1 ∼ C5b against five species of cancer cell which are Hela, MCF7, HepG2, Colo205, NCIsbnd H460 were tested respectively, the tests showed that C1 ∼ C5b exhibited significant anticancer activity for the cancer cells in comparison with the ligand, and the activity was greater than carboplatin.

The spectral cell method in nonlinear earthquake modeling

NASA Astrophysics Data System (ADS)

Giraldo, Daniel; Restrepo, Doriam

2017-12-01

This study examines the applicability of the spectral cell method (SCM) to compute the nonlinear earthquake response of complex basins. SCM combines fictitious-domain concepts with the spectral-version of the finite element method to solve the wave equations in heterogeneous geophysical domains. Nonlinear behavior is considered by implementing the Mohr-Coulomb and Drucker-Prager yielding criteria. We illustrate the performance of SCM with numerical examples of nonlinear basins exhibiting physically and computationally challenging conditions. The numerical experiments are benchmarked with results from overkill solutions, and using MIDAS GTS NX, a finite element software for geotechnical applications. Our findings show good agreement between the two sets of results. Traditional spectral elements implementations allow points per wavelength as low as PPW = 4.5 for high-order polynomials. Our findings show that in the presence of nonlinearity, high-order polynomials (p ≥ 3) require mesh resolutions above of PPW ≥ 10 to ensure displacement errors below 10%.

Chaperonin Containing-TCP-1 Protein Level in Breast Cancer Cells Predicts Therapeutic Application of a Cytotoxic Peptide

PubMed Central

Bassiouni, Rania; Nemec, Kathleen; Iketani, Ashley; Flores, Orielyz; Showalter, Anne; Khaled, Amr S.; Vishnubhotla, Priya; Sprung, Robert W.; Kaittanis, Charalambos; Perez, Jesus M.; Khaled, Annette R.

2016-01-01

Purpose Metastatic disease is a leading cause of death for patients with breast cancer, driving the need for new therapies. CT20p is a peptide previously discovered by our group that displays cancer-specific cytotoxicity. To design the optimal therapeutic use of the peptide, we identified the intracellular target of CT20p in breast cancer cells, correlating expression patterns of the target with susceptibility to CT20p. Experimental Design Using polymeric nanoparticles to deliver CT20p, we assessed cytoskeletal changes, cell migration, adhesion, and viability in cells treated with the peptide. Protein pull-down experiments, coupled to mass spectrometry, enabled identification of the peptide’s intracellular target. Biochemical and histological techniques validated target identity in human cell lines and breast cancer tissue microarrays and revealed susceptibility patterns to CT20p. Results Chaperonin Containing TCP-1 (CCT) was identified as the intracellular target of CT20p. Cancer cells susceptible to CT20p had increased CCT, and overexpression of CCTβ, a subunit of the CCT complex, enhanced susceptibility to CT20p. Susceptible cells displayed reduced tubulin, a substrate of CCT, and inhibition of migration upon CT20p treatment. CCTβ levels were higher in invasive ductal carcinomas than in cancer adjacent tissues and increased with breast cancer stage. Decreased breast cancer patient survival correlated with genomic alternations in CCTβ and higher levels of the chaperone. Conclusion Increased CCT protein in breast cancer cells underlies the cytotoxicity of CT20p. CCT is thus a potential target for therapeutic intervention and serves as a companion diagnostic to personalize the therapeutic use of CT20p for breast cancer treatment. PMID:27012814

75 FR 14604 - Guidance for Industry on Anesthetics for Companion Animals; Availability

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-26

...] Guidance for Industry on Anesthetics for Companion Animals; Availability AGENCY: Food and Drug... availability of Guidance for Industry 192 entitled ``Anesthetics for Companion Animals.'' This guidance makes recommendations for the development of anesthetic new animal drug products for companion animals. The guidance...

AP1 Keeps Chromatin Poised for Action | Center for Cancer Research

Cancer.gov

The human genome harbors gene-encoding DNA, the blueprint for building proteins that regulate cellular function. Embedded across the genome, in non-coding regions, are DNA elements to which regulatory factors bind. The interaction of regulatory factors with DNA at these sites modifies gene expression to modulate cell activity. In cells, DNA exists in a complex with proteins called chromatin that compacts the DNA in the nucleus, strongly restricting access to DNA sequences. As a result, regulatory factors only interact with a small subset of their potential binding elements in a given cell to regulate genes. How factors recognize and select sites in chromatin across the genome is not well understood -- but several discoveries in CCR’s Laboratory of Receptor Biology and Gene Expression (LRBGE) have shed light on the mechanisms that direct factors to DNA.

A globally well-posed finite element algorithm for aerodynamics applications

NASA Technical Reports Server (NTRS)

Iannelli, G. S.; Baker, A. J.

1991-01-01

A finite element CFD algorithm is developed for Euler and Navier-Stokes aerodynamic applications. For the linear basis, the resultant approximation is at least second-order-accurate in time and space for synergistic use of three procedures: (1) a Taylor weak statement, which provides for derivation of companion conservation law systems with embedded dispersion-error control mechanisms; (2) a stiffly stable second-order-accurate implicit Rosenbrock-Runge-Kutta temporal algorithm; and (3) a matrix tensor product factorization that permits efficient numerical linear algebra handling of the terminal large-matrix statement. Thorough analyses are presented regarding well-posed boundary conditions for inviscid and viscous flow specifications. Numerical solutions are generated and compared for critical evaluation of quasi-one- and two-dimensional Euler and Navier-Stokes benchmark test problems.

Searching For Low-mass Companions Of Cepheids

NASA Astrophysics Data System (ADS)

Remage Evans, Nancy; Bond, H.; Schaefer, G.; Karovska, M.; Mason, B.; DePasquale, J.; Pillitteri, I.; Guinan, E.; Engle, S.

2011-05-01

The role played by binary and multiple stars in star formation is receiving a great deal of attention, both theoretically and observationally. Two questions under discussion are how wide physical companions can be and how frequently massive stars have low mass companions. An important new observational tool is the development of high resolution imaging, both from space and from the ground (Adaptive Optics and interferometry). We are conducting a snapshot survey of the nearest Cepheids using the Hubble Space Telescope Wide Field Camera 3 (WFC3). The aim is to discover possible resolved low mass companions. Results from this survey will be discussed, including images of Eta Aql. X-ray luminosity can confirm or refute that putative low mass companions are young enough to be physical companions. This project tests the reality of both wide and low mass companions of these intermediate-mass stars.

Individual differences in children’s private speech: The role of imaginary companions

PubMed Central

Davis, Paige E.; Meins, Elizabeth; Fernyhough, Charles

2013-01-01

Relations between children’s imaginary companion status and their engagement in private speech during free play were investigated in a socially diverse sample of 5-year-olds (N = 148). Controlling for socioeconomic status, receptive verbal ability, total number of utterances, and duration of observation, there was a main effect of imaginary companion status on type of private speech. Children who had imaginary companions were more likely to engage in covert private speech compared with their peers who did not have imaginary companions. These results suggest that the private speech of children with imaginary companions is more internalized than that of their peers who do not have imaginary companions and that social engagement with imaginary beings may fulfill a similar role to social engagement with real-life partners in the developmental progression of private speech. PMID:23978382

Designed Proteins Induce the Formation of Nanocage-containing Extracellular Vesicles

PubMed Central

Votteler, Jörg; Ogohara, Cassandra; Yi, Sue; Hsia, Yang; Nattermann, Una; Belnap, David M.; King, Neil P.; Sundquist, Wesley I.

2017-01-01

Complex biological processes are often performed by self-organizing nanostructures comprising multiple classes of macromolecules, such as ribosomes (proteins and RNA) or enveloped viruses (proteins, nucleic acids, and lipids). Approaches have been developed for designing self-assembling structures consisting of either nucleic acids1,2 or proteins3–5, but strategies for engineering hybrid biological materials are only beginning to emerge6,7. Here, we describe the design of self-assembling protein nanocages that direct their own release from human cells inside small vesicles in a manner that resembles some viruses. We refer to these hybrid biomaterials as Enveloped Protein Nanocages (EPNs). Robust EPN biogenesis required protein sequence elements that encode three distinct functions: membrane binding, self-assembly, and recruitment of the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery8. A variety of synthetic proteins with these functional elements induced EPN biogenesis, highlighting the modularity and generality of the design strategy. Biochemical and electron cryomicroscopic (cryo-EM) analyses revealed that one design, EPN-01, comprised small (~100 nm) vesicles containing multiple protein nanocages that closely matched the structure of the designed 60-subunit self-assembling scaffold9. EPNs that incorporated the vesicular stomatitis viral glycoprotein (VSV-G) could fuse with target cells and deliver their contents, thereby transferring cargoes from one cell to another. These studies show how proteins can be programmed to direct the formation of hybrid biological materials that perform complex tasks, and establish EPNs as a novel class of designed, modular, genetically-encoded nanomaterials that can transfer molecules between cells. PMID:27919066

Impact of a volunteer companion program on nursing students' knowledge and concerns related to palliative care.

PubMed

Kwekkeboom, Kristine L; Vahl, Cheryl; Eland, Joann

2006-02-01

Deficiencies in end-of-life education may explain nursing students' reports of feeling anxious and unqualified to care for dying patients. A volunteer Palliative Care Companion program was developed to provide undergraduate nursing students with an experiential learning opportunity by spending time with dying patients and their families. To evaluate the impact of the Palliative Care Companion program on nursing students' knowledge, attitudes, and concerns about providing palliative care, and to describe companion students' volunteer activities. Quasiexperimental controlled pretest-posttest design. Fifty-two undergraduate nursing students (32 companion students, 20 controls) at a midwestern U.S. university with an affiliated hospital-based palliative care service. All participants completed the Palliative Care Quiz for Nurses, Attitudes Toward Palliative Care, and Concern About Caring for Dying Patients questionnaires at the beginning and end of the semester. Companion subjects also kept a journal describing their palliative care experiences. Attitude scores were not analyzed because of poor internal consistency of the questionnaire. Changes in scores on knowledge items did not reach significance. Concern scores decreased significantly from pretest to posttest in the companion group. After adjusting for pretest concern score, there was a trend toward lower concern score in the companion group compared to controls (p=0.07). Companion students' journals described activities including visiting patients, viewing end-of-life videos, attending educational and public lectures, independent reading, and making bereavement phone calls to family members. The Palliative Care Companion program did not produce significant improvements in knowledge and concerns compared to controls, but companion students described their participation as a meaningful learning experience.

The Health Technology Assessment of companion diagnostics: experience of NICE.

PubMed

Byron, Sarah K; Crabb, Nick; George, Elisabeth; Marlow, Mirella; Newland, Adrian

2014-03-15

Companion diagnostics are used to aid clinical decision making to identify patients who are most likely to respond to treatment. They are becoming increasingly important as more new pharmaceuticals receive licensed indications that require the use of a companion diagnostic to identify the appropriate patient subgroup for treatment. These pharmaceuticals have proven benefit in the treatment of some cancers and other diseases, and also have potential to precisely tailor treatments to the individual in the future. However, the increasing use of companion diagnostics could place a substantial burden on health system resources to provide potentially high volumes of testing. This situation, in part, has led policy makers and Health Technology Assessment (HTA) bodies to review the policies and methods used to make reimbursement decisions for pharmaceuticals requiring companion diagnostics. The assessment of a pharmaceutical alongside the companion diagnostic used in the clinical trials may be relatively straightforward, although there are a number of challenges associated with assessing pharmaceuticals where a range of alternative companion diagnostics are available for use in routine clinical practice. The UK HTA body, the National Institute for Health and Care Excellence (NICE), has developed policy for considering companion diagnostics using its Technology Appraisal and Diagnostics Assessment Programs. Some HTA bodies in other countries have also adapted their policies and methods to accommodate the assessment of companion diagnostics. Here, we provide insight into the HTA of companion diagnostics for reimbursement decisions and how the associated challenges are being addressed, in particular by NICE. See all articles in this CCR Focus section, "The Precision Medicine Conundrum: Approaches to Companion Diagnostic Co-development." ©2014 AACR.

[Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O is 2,6-dipicolinate and N,O is L-threoninate: synthesis, characterization, and biomedical properties.

PubMed

Chin, Lee-Fang; Kong, Siew-Ming; Seng, Hoi-Ling; Tiong, Yee-Lian; Neo, Kian-Eang; Maah, Mohd Jamil; Khoo, Alan Soo-Beng; Ahmad, Munirah; Hor, Tzi-Sum Andy; Lee, Hong-Boon; San, Swee-Lan; Chye, Soi-Moi; Ng, Chew-Hee

2012-10-01

Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.

CUB domain-containing protein 1 and the epidermal growth factor receptor cooperate to induce cell detachment.

PubMed

Law, Mary E; Ferreira, Renan B; Davis, Bradley J; Higgins, Paul J; Kim, Jae-Sung; Castellano, Ronald K; Chen, Sixue; Luesch, Hendrik; Law, Brian K

2016-08-05

While localized malignancies often respond to available therapies, most disseminated cancers are refractory. Novel approaches, therefore, are needed for the treatment of metastatic disease. CUB domain-containing protein1 (CDCP1) plays an important role in metastasis and drug resistance; the mechanism however, is poorly understood. Breast cancer cell lines were engineered to stably express EGFR, CDCP1 or phosphorylation site mutants of CDCP1. These cell lines were used for immunoblot analysis or affinity purification followed by immunoblot analysis to assess protein phosphorylation and/or protein complex formation with CDCP1. Kinase activity was evaluated using phosphorylation site-specific antibodies and immunoblot analysis in in vitro kinase assays. Protein band excision and mass spectrometry was utilized to further identify proteins complexed with CDCP1 or ΔCDCP1, which is a mimetic of the cleaved form of CDCP1. Cell detachment was assessed using cell counting. This paper reports that CDCP1 forms ternary protein complexes with Src and EGFR, facilitating Src activation and Src-dependent EGFR transactivation. Importantly, we have discovered that a class of compounds termed Disulfide bond Disrupting Agents (DDAs) blocks CDCP1/EGFR/Src ternary complex formation and downstream signaling. CDCP1 and EGFR cooperate to induce detachment of breast cancer cells from the substratum and to disrupt adherens junctions. Analysis of CDCP1-containing complexes using proteomics techniques reveals that CDCP1 associates with several proteins involved in cell adhesion, including adherens junction and desmosomal cadherins, and cytoskeletal elements. Together, these results suggest that CDCP1 may facilitate loss of adhesion by promoting activation of EGFR and Src at sites of cell-cell and cell-substratum contact.

45 CFR 2551.72 - Is a written volunteer assignment plan required for each volunteer?

Code of Federal Regulations, 2010 CFR

2010-10-01

... such services; and (5) Is used to review the status of the Senior Companion's services in working with... (Continued) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Senior Companion...) All Senior Companions performing direct services to individual clients in home settings and individual...

Whole genome sequencing of Escherichia coli encoding blaNDM isolated from humans and companion animals in Egypt

USDA-ARS?s Scientific Manuscript database

Companion animals are a source of zoonotic infections and especially important considering the potential of companion animals to harbor antibiotic resistant pathogens. In this study, blaNDM positive Escherichia coli from companion animals, humans, and the environment from Mansoura, Egypt were charac...

A Good Story: Children with Imaginary Companions Create Richer Narratives

ERIC Educational Resources Information Center

Trionfi, Gabriel; Reese, Elaine

2009-01-01

In line with theories that children's pretend play reflects and extends their narrative skills, children with imaginary companions were predicted to have better narrative skills than children without imaginary companions. Forty-eight 5 1/2-year-old children and their mothers participated in interviews about children's imaginary companions.…

Transition metal complexes of a new 15-membered [N5] penta-azamacrocyclic ligand with their spectral and anticancer studies

NASA Astrophysics Data System (ADS)

El-Boraey, Hanaa A.; Serag El-Din, Azza A.

2014-11-01

Novel penta-azamacrocyclic 15-membered [N5] ligand [L] i.e. 1,5,8,12-tetetraaza-3,4: 9,10-dibenzo-6-ethyl-7-methyl-1,12-(2,6-pyrido)cyclopentadecan-5,7 diene-2,11-dione and its transition metal complexes with Co(II), Ni(II), Cu(II), Ru(III) and Pd(II) have been synthesized and structurally characterized by elemental analysis, spectral, thermal as well as magnetic and molar conductivity measurements. On basis of IR, MS, UV-Vis 1H NMR and EPR spectral studies an octahedral geometry has been proposed for all complexes except Co(II), Cu(II) nitrate complexes and Pd(II) chloride complex that adopt tetrahedral, square pyramidal and square planar geometries, respectively. The antitumor activity of the synthesized ligand and some complexes against human breast cancer cell lines (MCF-7) and human hepatocarcinoma cell lines (HepG2) has been studied. The complexes (IC50 = 2.04-9.7, 2.5-3.7 μg/mL) showed potent antitumor activity comparable with their ligand (IC50 = 11.7, 3.45 μg/mL) against the above mentioned cell lines, respectively. The results evidently show that the activity of the ligand becomes more pronounced and significant when coordinated to the metal ion.

High cell density media for Escherichia coli are generally designed for aerobic cultivations – consequences for large-scale bioprocesses and shake flask cultures

PubMed Central

Soini, Jaakko; Ukkonen, Kaisa; Neubauer, Peter

2008-01-01

Background For the cultivation of Escherichia coli in bioreactors trace element solutions are generally designed for optimal growth under aerobic conditions. They do normally not contain selenium and nickel. Molybdenum is only contained in few of them. These elements are part of the formate hydrogen lyase (FHL) complex which is induced under anaerobic conditions. As it is generally known that oxygen limitation appears in shake flask cultures and locally in large-scale bioreactors, function of the FHL complex may influence the process behaviour. Formate has been described to accumulate in large-scale cultures and may have toxic effects on E. coli. Although the anaerobic metabolism of E. coli is well studied, reference data which estimate the impact of the FHL complex on bioprocesses of E. coli with oxygen limitation have so far not been published, but are important for a better process understanding. Results Two sets of fed-batch cultures with conditions triggering oxygen limitation and formate accumulation were performed. Permanent oxygen limitation which is typical for shake flask cultures was caused in a bioreactor by reduction of the agitation rate. Transient oxygen limitation, which has been described to eventually occur in the feed-zone of large-scale bioreactors, was mimicked in a two-compartment scale-down bioreactor consisting of a stirred tank reactor and a plug flow reactor (PFR) with continuous glucose feeding into the PFR. In both models formate accumulated up to about 20 mM in the culture medium without addition of selenium, molybdenum and nickel. By addition of these trace elements the formate accumulation decreased below the level observed in well-mixed laboratory-scale cultures. Interestingly, addition of the extra trace elements caused accumulation of large amounts of lactate and reduced biomass yield in the simulator with permanent oxygen limitation, but not in the scale-down two-compartment bioreactor. Conclusion The accumulation of formate in oxygen limited cultivations of E. coli can be fully prevented by addition of the trace elements selenium, nickel and molybdenum, necessary for the function of FHL complex. For large-scale cultivations, if glucose gradients are likely, the results from the two-compartment scale-down bioreactor indicate that the addition of the extra trace elements is beneficial. No negative effects on the biomass yield or on any other bioprocess parameters could be observed in cultures with the extra trace elements if the cells were repeatedly exposed to transient oxygen limitation. PMID:18687130

Calibrated complex impedance of CHO cells and E. coli bacteria at GHz frequencies using scanning microwave microscopy

NASA Astrophysics Data System (ADS)

Tuca, Silviu-Sorin; Badino, Giorgio; Gramse, Georg; Brinciotti, Enrico; Kasper, Manuel; Oh, Yoo Jin; Zhu, Rong; Rankl, Christian; Hinterdorfer, Peter; Kienberger, Ferry

2016-04-01

The application of scanning microwave microscopy (SMM) to extract calibrated electrical properties of cells and bacteria in air is presented. From the S 11 images, after calibration, complex impedance and admittance images of Chinese hamster ovary cells and E. coli bacteria deposited on a silicon substrate have been obtained. The broadband capabilities of SMM have been used to characterize the bio-samples between 2 GHz and 20 GHz. The resulting calibrated cell and bacteria admittance at 19 GHz were Y cell = 185 μS + j285 μS and Y bacteria = 3 μS + j20 μS, respectively. A combined circuitry-3D finite element method EMPro model has been developed and used to investigate the frequency response of the complex impedance and admittance of the SMM setup. Based on a proposed parallel resistance-capacitance model, the equivalent conductance and parallel capacitance of the cells and bacteria were obtained from the SMM images. The influence of humidity and frequency on the cell conductance was experimentally studied. To compare the cell conductance with bulk water properties, we measured the imaginary part of the bulk water loss with a dielectric probe kit in the same frequency range resulting in a high level of agreement.

House sparrows' (Passer domesticus) behaviour in a novel environment is modulated by social context and familiarity in a sex-specific manner.

PubMed

Tuliozi, Beniamino; Fracasso, Gerardo; Hoi, Herbert; Griggio, Matteo

2018-01-01

Exploratory behaviour is one of the best-investigated behavioural traits. However, little is known about how differences in familiarity, i.e. in the knowledge and previous experience with a companion can influence the exploration of a novel environment. However, to our knowledge, such a critical feature of the social environment has never been the target of a study relating it to exploratory behaviour in birds. Here we examined if familiarity with a conspecific could affect behavioural responses of individuals confronted with a novel environment. We recorded the latency to land on the ground, latency to feed, time spent feeding and number of sectors visited of 48 female and 48 male house sparrows ( Passer domesticus ) in an indoor aviary in three contexts: alone (individual context), with an unfamiliar and with a familiar same-sex companion. House sparrows landed sooner on the ground when in the familiar context than when in the individual context. Birds in unfamiliar pairs followed each other less than familiar birds, but this difference diminished with time spent exploring. Moreover, males and females differed in their behavioural responses in the unfamiliar context. Females with a familiar companion landed sooner than when they were paired with an unfamiliar conspecific, whereas only the presence of a companion but not familiarity reduced males latency to land on the ground. Finally, when considering the unfamiliar context males had shorter latencies to forage and thus spent more time eating than females. The presence or absence of a companion and its familiarity with the focal individual influenced differently the behavioural responses of male and female house sparrows in a novel environment. As house sparrows are strongly sociable, the influence of the social environment is likely to be of paramount importance to understand the selective pressures acting on them, particularly in recently colonized areas with ephemeral food sources. Our results shed light on the complex influence that the social environment has on the behavioural responses of a cosmopolitan bird.

Design and evaluation of a new Peltier-cooled laser ablation cell with on-sample temperature control.

PubMed

Konz, Ioana; Fernández, Beatriz; Fernández, M Luisa; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-01-27

A new custom-built Peltier-cooled laser ablation cell is described. The proposed cryogenic cell combines a small internal volume (20 cm(3)) with a unique and reliable on-sample temperature control. The use of a flexible temperature sensor, directly located on the sample surface, ensures a rigorous sample temperature control throughout the entire analysis time and allows instant response to any possible fluctuation. In this way sample integrity and, therefore, reproducibility can be guaranteed during the ablation. The refrigeration of the proposed cryogenic cell combines an internal refrigeration system, controlled by a sensitive thermocouple, with an external refrigeration system. Cooling of the sample is directly carried out by 8 small (1 cm×1 cm) Peltier elements placed in a circular arrangement in the base of the cell. These Peltier elements are located below a copper plate where the sample is placed. Due to the small size of the cooling electronics and their circular allocation it was possible to maintain a peephole under the sample for illumination allowing a much better visualization of the sample, a factor especially important when working with structurally complex tissue sections. The analytical performance of the cryogenic cell was studied using a glass reference material (SRM NIST 612) at room temperature and at -20°C. The proposed cell design shows a reasonable signal washout (signal decay within less than 10 s to background level), high sensitivity and good signal stability (in the range 6.6-11.7%). Furthermore, high precision (0.4-2.6%) and accuracy (0.3-3.9%) in the isotope ratio measurements were also observed operating the cell both at room temperature and at -20°C. Finally, experimental results obtained for the cell application to qualitative elemental imaging of structurally complex tissue samples (e.g. eye sections from a native frozen porcine eye and fresh flower leaves) demonstrate that working in cryogenic conditions is critical in such type of direct sample analysis. Copyright © 2013 Elsevier B.V. All rights reserved.

A minimal mathematical model combining several regulatory cycles from the budding yeast cell cycle.

PubMed

Sriram, K; Bernot, G; Képès, F

2007-11-01

A novel topology of regulatory networks abstracted from the budding yeast cell cycle is studied by constructing a simple nonlinear model. A ternary positive feedback loop with only positive regulations is constructed with elements that activates the subsequent element in a clockwise fashion. A ternary negative feedback loop with only negative regulations is constructed with the elements that inhibit the subsequent element in an anticlockwise fashion. Positive feedback loop exhibits bistability, whereas the negative feedback loop exhibits limit cycle oscillations. The novelty of the topology is that the corresponding elements in these two homogeneous feedback loops are linked by the binary positive feedback loops with only positive regulations. This results in the emergence of mixed feedback loops in the network that displays complex behaviour like the coexistence of multiple steady states, relaxation oscillations and chaos. Importantly, the arrangement of the feedback loops brings in the notion of checkpoint in the model. The model also exhibits domino-like behaviour, where the limit cycle oscillations take place in a stepwise fashion. As the aforementioned topology is abstracted from the budding yeast cell cycle, the events that govern the cell cycle are considered for the present study. In budding yeast, the sequential activation of the transcription factors, cyclins and their inhibitors form mixed feedback loops. The transcription factors that involve in the positive regulation in a clockwise orientation generates ternary positive feedback loop, while the cyclins and their inhibitors that involve in the negative regulation in an anticlockwise orientation generates ternary negative feedback loop. The mutual regulation between the corresponding elements in the transcription factors and the cyclins and their inhibitors generates binary positive feedback loops. The bifurcation diagram constructed for the whole system can be related to the different events of the cell cycle in terms of dynamical system theory. The checkpoint mechanism that plays an important role in different phases of the cell cycle are accounted for by silencing appropriate feedback loops in the model.

Unstructured Cartesian/prismatic grid generation for complex geometries

NASA Technical Reports Server (NTRS)

Karman, Steve L., Jr.

1995-01-01

The generation of a hybrid grid system for discretizing complex three dimensional (3D) geometries is described. The primary grid system is an unstructured Cartesian grid automatically generated using recursive cell subdivision. This grid system is sufficient for computing Euler solutions about extremely complex 3D geometries. A secondary grid system, using triangular-prismatic elements, may be added for resolving the boundary layer region of viscous flows near surfaces of solid bodies. This paper describes the grid generation processes used to generate each grid type. Several example grids are shown, demonstrating the ability of the method to discretize complex geometries, with very little pre-processing required by the user.

Mitochondrial complex II is a source of the reserve respiratory capacity that is regulated by metabolic sensors and promotes cell survival.

PubMed

Pfleger, J; He, M; Abdellatif, M

2015-07-30

The survival of a cell depends on its ability to meet its energy requirements. We hypothesized that the mitochondrial reserve respiratory capacity (RRC) of a cell is a critical component of its bioenergetics that can be utilized during an increase in energy demand, thereby, enhancing viability. Our goal was to identify the elements that regulate and contribute to the development of RRC and its involvement in cell survival. The results show that activation of metabolic sensors, including pyruvate dehydrogenase and AMP-dependent kinase, increases cardiac myocyte RRC via a Sirt3-dependent mechanism. Notably, we identified mitochondrial complex II (cII) as a target of these metabolic sensors and the main source of RRC. Moreover, we show that RRC, via cII, correlates with enhanced cell survival after hypoxia. Thus, for the first time, we show that metabolic sensors via Sirt3 maximize the cellular RRC through activating cII, which enhances cell survival after hypoxia.

Cepheid binaries with large mass ratios (M1/M2)

NASA Technical Reports Server (NTRS)

Evans, Nancy Remage

1988-01-01

The IUE observations of 3 Cepheid systems (Polaris, FF Aql, and S Sge) are used to derive, or set limits on, the temperatures and masses of the companions. Light from the companions of FF Aql and S Sge from 1700 to 2000 A is consistent with an A5 to A7 main sequence companion for both Cepheids, with a mass of 1.8 solar mass. This mass for the companion of S Sge is smaller than required by the orbital mass function and an evolutionary mass of the Cepheid, suggesting that the companion may itself be a binary. For Polaris, the mass of the companion must be less than 1.8 solar mass.

Transforming growth factor β suppresses peroxisome proliferator-activated receptor γ expression via both SMAD binding and novel TGF-β inhibitory elements.

PubMed

Lakshmi, Sowmya P; Reddy, Aravind T; Reddy, Raju C

2017-04-24

Transforming growth factor β (TGF-β) contributes to wound healing and, when dysregulated, to pathological fibrosis. TGF-β and the anti-fibrotic nuclear hormone receptor peroxisome proliferator-activated receptor γ (PPARγ) repress each other's expression, and such PPARγ down-regulation is prominent in fibrosis and mediated, via previously unknown SMAD-signaling mechanisms. Here, we show that TGF-β induces the association of SMAD3 with both SMAD4, needed for translocation of the complex into the nucleus, and the essential context-sensitive co-repressors E2F4 and p107. The complex mediates TGF-β-induced repression by binding to regulatory elements in the target promoter. In the PPARG promoter, we found that the SMAD3-SMAD4 complex binds both to a previously unknown consensus TGF-β inhibitory element (TIE) and also to canonical SMAD-binding elements (SBEs). Furthermore, the TIE and SBEs independently mediated the partial repression of PPARG transcription, the first demonstration of a TIE and SBEs functioning within the same promoter. Also, TGF-β-treated fibroblasts contained SMAD complexes that activated a SMAD target gene in addition to those repressing PPARG transcription, the first finding of such dual activity within the same cell. These findings describe in detail novel mechanisms by which TGF-β represses PPARG transcription, thereby facilitating its own pro-fibrotic activity. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

Detection of a compact companion of the mild barium star Xi-1 Ceti

NASA Technical Reports Server (NTRS)

Bohm-Vitense, E.; Johnson, H. R.

1985-01-01

In the present paper, the observation of a white dwarf companion of the mild Ba star Xi-1 Ceti (= 65 Ceti = HR 649 = HD 13611) is reported, taking into account also the properties of the mild Ba star and of its companion. The UV spectrum of Xi-1 Ceti is discussed along with an interpretation of this spectrum. Attention is given to the effective temperature of the companion, the absorption bands in the spectrum, the radius and mass of the Xi-1 Ceti companion, and questions regarding the obscuration of the companion by the atmosphere of the Ba star. It is found that the overall energy distribution of the Xi-1 Ceti companion can best be matched with a 14,000 K DA white dwarf of log g = 8 or less. However, the absolute intensity is too small and would require a radius too small and a mass too large for such a gravity.

Assessing the Effect of Stellar Companions to Kepler Objects of Interest

NASA Astrophysics Data System (ADS)

Hirsch, Lea; Ciardi, David R.; Howard, Andrew

2017-01-01

Unknown stellar companions to Kepler planet host stars dilute the transit signal, causing the planetary radii to be underestimated. We report on the analysis of 165 stellar companions detected with high-resolution imaging to be within 2" of 159 KOI host stars. The majority of the planets and planet candidates in these systems have nominal radii smaller than 6 REarth. Using multi-filter photometry on each companion, we assess the likelihood that the companion is bound and estimate its stellar properties, including stellar radius and flux. We then recalculate the planet radii in these systems, determining how much each planet's size is underestimated if it is assumed to 1) orbit the primary star, 2) orbit the companion star, or 3) be equally likely to orbit either star in the system. We demonstrate the overall effect of unknown stellar companions on our understanding of Kepler planet sizes.

45 CFR 2551.111 - Under what conditions can an agency or organization sponsor a Senior Companion project without...

Code of Federal Regulations, 2010 CFR

2010-10-01

... organization sponsor a Senior Companion project without Corporation funding? 2551.111 Section 2551.111 Public... SENIOR COMPANION PROGRAM Non-Corporation Funded SCP Projects § 2551.111 Under what conditions can an agency or organization sponsor a Senior Companion project without Corporation funding? An eligible agency...

Encouraging Student Reflection and Articulation Using a Learning Companion: A Commentary

ERIC Educational Resources Information Center

Goodman, Bradley; Linton, Frank; Gaimari, Robert

2016-01-01

Our 1998 paper "Encouraging Student Reflection and Articulation using a Learning Companion" (Goodman et al. 1998) was a stepping stone in the progression of learning companions for intelligent tutoring systems (ITS). A simulated learning companion, acting as a peer in an intelligent tutoring environment ensures the availability of a…

NEW BROWN DWARF COMPANIONS TO YOUNG STARS IN SCORPIUS-CENTAURUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Janson, Markus; Jayawardhana, Ray; Bonavita, Mariangela

2012-10-10

We present the discoveries of three faint companions to young stars in the Scorpius-Centaurus region, imaged with the NICI instrument on Gemini South. We have confirmed all three companions through common proper motion tests. Follow-up spectroscopy has confirmed two of them, HIP 65423 B and HIP 65517 B, to be brown dwarfs, while the third, HIP 72099 B, is more likely a very low mass star just above the hydrogen burning limit. The detection of wide companions in the mass range of {approx}40-100 M{sub jup} complements previous work in the same region, reporting detections of similarly wide companions with lowermore » masses, in the range of {approx}10-30 M{sub jup}. Such low masses near the deuterium burning limit have raised the question of whether those objects formed like planets or stars. The existence of intermediate objects as reported here could represent a bridge between lower-mass companions and stellar companions, but in any case demonstrate that mass alone may not provide a clear-cut distinction for the formation of low-mass companions to stars.« less

Companion Animals in Natural Disasters: A Scoping Review of Scholarly Sources.

PubMed

Travers, Cheryl; Degeling, Chris; Rock, Melanie

2017-01-01

During a disaster, people may make evacuation decisions based on their companion animal's welfare, therefore exposing themselves, their companion animals, and emergency responders to increased risk for injury or death. The loss and suffering of companion animals in disasters causes deep distress, diminishing people's capacity to rebuild their lives. This scoping review presents scholarly research studies and reviews relating to people and their companion animals in the context of disasters, with an aim of informing researchers, policymakers, and practitioners and providing direction for future research. Using the Arksey and O'Malley framework, articles in scholarly journals from 2004 to 2014 are discussed. Analysis included 38 articles: 20 research studies, 12 reviews, and 6 editorials. Findings revealed 2 central themes: companion animals as a risk factor to human health and safety and companion animals being "at risk" themselves. An emerging theme was "responsibility": Who is responsible for companion animals in disasters and how? Understanding the implications of human-nonhuman animal relationships for disaster response and having a broader public consensus on what is owed to animals at times of emergency are important to community preparedness and resilience.

MicroRNA-let-7a regulates cell autophagy by targeting Rictor in gastric cancer cell lines MGC-803 and SGC-7901.

PubMed

Fan, Hao; Jiang, Mingkun; Li, Bowen; He, Yu; Huang, Chi; Luo, Dakui; Xu, Hao; Yang, Li; Zhou, Jundong

2018-03-01

miR-let-7a is the most widely studied miRNA, whose functions have been well-established by scientists in both carcinogenesis and progression of human cancer, including gastric cancer (GC). However, to date there is a lack of information concerning the relationship between miR-let-7a and cellular autophagy. Using western blotting and immunofluorescence, we determined that upregulation of miR-let-7a led to increased cellular autophagic level, whereas miR-let-7a suppression decreased autophagy activity in GC cells. To further elucidate the mechanisms underlying this, we screened potential targets of miR-let-7a using bioinformatics analyses, validated by a series of assays. Our results indicated that Rptor independent companion of mTOR complex 2 (Rictor) was a direct target of miR-let-7a. In addition, rescue experiments in vitro showed that miR-let-7a promoted cellular autophagic level by inhibiting Rictor expression in GC cells. Furthermore, as an upstream executor of Akt-mTOR signaling pathway, we found that Rictor elaborated its effect on autophagy by phosphorylating Akt and mTOR, and this regulatory process could also be mediated by miR-let-7a. Taken together, our results present a novel role for miR-let-7a in GC which modulates autophagy by targeting Rictor, following the regulation of Akt-mTOR signal pathway.

TGF-{beta} signals the formation of a unique NF1/Smad4-dependent transcription repressor-complex in human diploid fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Luciakova, Katarina, E-mail: katarina.luciakova@savba.sk; Kollarovic, Gabriel; Kretova, Miroslava

2011-08-05

Highlights: {yields} TGF-{beta} induces the formation of unique nuclear NF1/Smad4 complexes that repress expression of the ANT-2 gene. {yields} Repression is mediated through an NF1-dependent repressor element in the promoter. {yields} The formation of NF1/Smad4 complexes and the repression of ANT2 are prevented by inhibitors of p38 kinase and TGF-{beta} RI. {yields} NF1/Smad complexes implicate novel role for NF1 and Smad proteins in the regulation of growth. -- Abstract: We earlier reported the formation of a unique nuclear NF1/Smad complex in serum-restricted fibroblasts that acts as an NF1-dependent repressor of the human adenine nucleotide translocase-2 gene (ANT2) [K. Luciakova, G.more » Kollarovic, P. Barath, B.D. Nelson, Growth-dependent repression of human adenine nucleotide translocator-2 (ANT2) transcription: evidence for the participation of Smad and Sp family proteins in the NF1-dependent repressor complex, Biochem. J. 412 (2008) 123-130]. In the present study, we show that TGF-{beta}, like serum-restriction: (a) induces the formation of NF1/Smad repressor complexes, (b) increases binding of the complexes to the repressor elements (Go elements) in the ANT2 promoter, and (c) inhibits ANT2 expression. Repression of ANT2 by TGF-{beta} is eliminated by mutating the NF1 binding sites in the Go repressor elements. All of the above responses to TGF-{beta} are prevented by inhibitors of TGF-{beta} RI and MAPK p38. These inhibitors also prevent NF1/Smad4 repressor complex formation and repression of ANT2 expression in serum-restricted cells, suggesting that similar signaling pathways are initiated by TGF-{beta} and serum-restriction. The present finding that NF1/Smad4 repressor complexes are formed through TGF-{beta} signaling pathways suggests a new, but much broader, role for these complexes in the initiation or maintenance of the growth-inhibited state.« less

Diagnosis and treatment of diffuse large B-cell lymphoma in an orangutan (Pongo pygmaeus).

PubMed

Ikpatt, Offiong F; Reavill, Drury; Chatfield, Jason; Clubb, Susan; Rosenblatt, Joseph D; Fonte, Glenn; Fan, Yao-Shan; Cray, Carolyn

2014-12-01

Lymphoma is a common malignancy observed in companion animals. This type of naturally occurring neoplasia has been uncommonly reported in great apes. Diffuse large B-cell lymphoma was diagnosed in an 8-yr-old captive orangutan (Pongo pygmaeus) with gastrointestinal disease by histologic and immunohistochemical methodologies. The orangutan was treated with three cycles of combination chemotherapy (intravenous Rituxan, cyclophosphamide, doxorubicin, and vincristine). The primate has been in good health and exhibiting normal behaviors for more than 15 mo following treatment.

Arabidopsis thaliana is a susceptible host plant for the holoparasite Cuscuta spec.

PubMed

Birschwilks, Mandy; Sauer, Norbert; Scheel, Dierk; Neumann, Stefanie

2007-10-01

Arabidopsis thaliana and Cuscuta spec. represent a compatible host-parasite combination. Cuscuta produces a haustorium that penetrates the host tissue. In early stages of development the searching hyphae on the tip of the haustorial cone are connected to the host tissue by interspecific plasmodesmata. Ten days after infection, translocation of the fluorescent dyes, Texas Red (TR) and 5,6-carboxyfluorescein (CF), demonstrates the existence of a continuous connection between xylem and phloem of the host and parasite. Cuscuta becomes the dominant sink in this host-parasite system. Transgenic Arabidopsis plants expressing genes encoding the green fluorescent protein (GFP; 27 kDa) or a GFP-ubiquitin fusion (36 kDa), respectively, under the companion cell (CC)-specific AtSUC2 promoter were used to monitor the transfer of these proteins from the host sieve elements to those of Cuscuta. Although GFP is transferred unimpedly to the parasite, the GFP-ubiquitin fusion could not be detected in Cuscuta. A translocation of the GFP-ubiquitin fusion protein was found to be restricted to the phloem of the host, although a functional symplastic pathway exists between the host and parasite, as demonstrated by the transport of CF. These results indicate a peripheral size exclusion limit (SEL) between 27 and 36 kDa for the symplastic connections between host and Cuscuta sieve elements. Forty-six accessions of A. thaliana covering the entire range of its genetic diversity, as well as Arabidopsis halleri, were found to be susceptible towards Cuscuta reflexa.

Endothelial Progenitor Cells=EPC=Elemental Pernicious Complexity

PubMed Central

Ushio-Fukai, Masuko

2011-01-01

Abstract Endothelial progenitor cells (EPCs) represent a heterogeneous population of cells with a pro-angiogenic potential that are derived not only from bone marrow but also from other tissues. Depending on the model and cell type used, the pro-angiogenic effect is a consequence of direct vascular integration, the paracrine release of growth factors and cytokines, or complex interactions with other cellular components like monocytes or platelets. The pro-angiogenic potential of EPCs is dependent on the particular type of EPC studied and modulated by the risk and life style factors of the patient as well as by local factors determining the homing to diseased tissue and the EPC proteome. In this Forum on EPCs these aspects will be covered in individual review articles, which are accompanied by two original research studies on the role of NADPH oxidases for EPC mobilization and the impact of organic nitrates on EPCs. Antioxid. Redox Signal. 15, 911–914. PMID:21128729

Resolved Companions of Cepheids: Testing the Candidates with X-Ray Observations

NASA Astrophysics Data System (ADS)

Evans, Nancy Remage; Pillitteri, Ignazio; Wolk, Scott; Karovska, Margarita; Tingle, Evan; Guinan, Edward; Engle, Scott; Bond, Howard E.; Schaefer, Gail H.; Mason, Brian D.

2016-04-01

We have made XMM-Newton observations of 14 Galactic Cepheids that have candidate resolved (≥5″) companion stars based on our earlier HST Wide Field Camera 3 (WFC3) imaging survey. Main-sequence stars that are young enough to be physical companions of Cepheids are expected to be strong X-ray producers in contrast to field stars. XMM-Newton exposures were set to detect essentially all companions hotter than spectral type M0 (corresponding to 0.5 M⊙). The large majority of our candidate companions were not detected in X-rays, and hence are not confirmed as young companions. One resolved candidate (S Nor #4) was unambiguously detected, but the Cepheid is a member of a populous cluster. For this reason, it is likely that S Nor #4 is a cluster member rather than a gravitationally bound companion. Two further Cepheids (S Mus and R Cru) have X-ray emission that might be produced by either the Cepheid or the candidate resolved companion. A subsequent Chandra observation of S Mus shows that the X-rays are at the location of the Cepheid/spectroscopic binary. R Cru and also V659 Cen (also X-ray bright) have possible companions closer than 5″ (the limit for this study) which are the likely sources of X-rays. One final X-ray detection (V473 Lyr) has no known optical companion, so the prime suspect is the Cepheid itself. It is a unique Cepheid with a variable amplitude. The 14 stars that we observed with XMM constitute 36% of the 39 Cepheids found to have candidate companions in our HST/WFC3 optical survey. No young probable binary companions were found with separations of ≥5″ or 4000 au. Based on observations obtained with XMM-Newton, an ESA science mission with instruments and contributions directly funded by ESA Member States and the USA (NASA).

Wide cool and ultracool companions to nearby stars from Pan-STARRS 1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deacon, Niall R.; Liu, Michael C.; Magnier, Eugene A.

2014-09-10

We present the discovery of 57 wide (>5'') separation, low-mass (stellar and substellar) companions to stars in the solar neighborhood identified from Pan-STARRS 1 (PS1) data and the spectral classification of 31 previously known companions. Our companions represent a selective subsample of promising candidates and span a range in spectral type of K7-L9 with the addition of one DA white dwarf. These were identified primarily from a dedicated common proper motion search around nearby stars, along with a few as serendipitous discoveries from our Pan-STARRS 1 brown dwarf search. Our discoveries include 23 new L dwarf companions and one knownmore » L dwarf not previously identified as a companion. The primary stars around which we searched for companions come from a list of bright stars with well-measured parallaxes and large proper motions from the Hipparcos catalog (8583 stars, mostly A-K dwarfs) and fainter stars from other proper motion catalogs (79170 stars, mostly M dwarfs). We examine the likelihood that our companions are chance alignments between unrelated stars and conclude that this is unlikely for the majority of the objects that we have followed-up spectroscopically. We also examine the entire population of ultracool (>M7) dwarf companions and conclude that while some are loosely bound, most are unlikely to be disrupted over the course of ∼10 Gyr. Our search increases the number of ultracool M dwarf companions wider than 300 AU by 88% and increases the number of L dwarf companions in the same separation range by 82%. Finally, we resolve our new L dwarf companion to HIP 6407 into a tight (0.''13, 7.4 AU) L1+T3 binary, making the system a hierarchical triple. Our search for these key benchmarks against which brown dwarf and exoplanet atmosphere models are tested has yielded the largest number of discoveries to date.« less

Self Assessment: Increasing the Effectiveness of Postsecondary Coordination. A Companion to "On Balance: Lessons in Effective Coordination from the Washington State Board for Community and Technical Colleges--An Organizational Perspective"

ERIC Educational Resources Information Center

Kirlin, Mary; Shulock, Nancy

2012-01-01

Public organizations charged with coordinating higher education institutions face a complex set of tasks. Whether coordinating institutions within one sector or across sectors, such organizations play vital roles in promoting a state's capacity for policy leadership to meet the growing need for an educated citizenry. National experts have…

The 3’-Jα Region of the TCRα Locus Bears Gene Regulatory Activity in Thymic and Peripheral T Cells

PubMed Central

Kučerová-Levisohn, Martina; Knirr, Stefan; Mejia, Rosa I.; Ortiz, Benjamin D.

2015-01-01

Much progress has been made in understanding the important cis-mediated controls on mouse TCRα gene function, including identification of the Eα enhancer and TCRα locus control region (LCR). Nevertheless, previous data have suggested that other cis-regulatory elements may reside in the locus outside of the Eα/LCR. Based on prior findings, we hypothesized the existence of gene regulatory elements in a 3.9-kb region 5’ of the Cα exons. Using DNase hypersensitivity assays and TCRα BAC reporter transgenes in mice, we detected gene regulatory activity within this 3.9-kb region. This region is active in both thymic and peripheral T cells, and selectively affects upstream, but not downstream, gene expression. Together, these data indicate the existence of a novel cis-acting regulatory complex that contributes to TCRα transgene expression in vivo. The active chromatin sites we discovered within this region would remain in the locus after TCRα gene rearrangement, and thus may contribute to endogenous TCRα gene activity, particularly in peripheral T cells, where the Eα element has been found to be inactive. PMID:26177549

Transcriptional regulation of human MUC4 gene: identification of a novel inhibitory element and its nuclear binding protein.

PubMed

Zhang, Jing-Jing; Zhu, Yi; Zhang, Xiong-Fei; Liang, Wen-Biao; Xie, Kun-Ling; Tao, Jin-Qiu; Peng, Yun-Peng; Xu, Ze-Kuan; Miao, Yi

2013-08-01

The human mucin 4 (MUC4) is aberrantly expressed in pancreatic adenocarcinoma and tumor cell lines, while remaining undetectable in normal pancreas, indicating its important role in pancreatic cancer development. Although its transcriptional regulation has been investigated in considerable detail, some important elements remain unknown. The aim of the present study was to demonstrate the existence of a novel inhibitory element in the MUC4 promoter and characterize some of its binding proteins. By luciferase reporter assay, we located the inhibitory element between nucleotides -2530 and -2521 in the MUC4 promoter using a series of deletion and mutant reporter constructs. Electrophoretic mobility shift assay (EMSA) with Bxpc-3 cell nuclear extracts revealed that one protein or protein complex bind to this element. The proteins binding to this element were purified and identified as Yin Yang 1 (YY1) by mass spectrometry. Supershift assay and chromatin immunoprecipitation (ChIP) assay confirmed that YY1 binds to this element in vitro and in vivo. Moreover, transient YY1 overexpression significantly inhibited MUC4 promoter activity and endogenous MUC4 protein expression. In conclusion, we reported here a novel inhibitory element in the human MUC4 promoter. This provides additional data on MUC4 gene regulation and indicates that YY1 may be a potential target for abnormal MUC4 expression.

Induction of polyclonal antibody synthesis by human allogeneic and autologous helper factors

PubMed Central

1979-01-01

Human helper factors were obtained from supernates of 48 h unidirectional allogeneic and autologous mixed lymphocyte reactions. These supernates were shown to induce the production of large amounts of immunoglobulin by tonsillar and peripheral blood mononuclear cells. Abundant polyclonal activation to antibody production occurred in these cultures in the absence of antigenic challenge which was similar in degree to that produced by pokeweed mitogen. This was documented by quantitating plasma cells, specific plaque-forming cells, and secreted immunoglobulin. In addition, the supplementation of companion cultures with sheep erythrocytes resulted in a significant enhancement of the specific plaque-forming cell response without an appreciable change in plasma cell number of secreted Ig. PMID:156242

Trace element distribution in the rat cerebellum

NASA Astrophysics Data System (ADS)

Kwiatek, W. M.; Long, G. J.; Pounds, J. G.; Reuhl, K. R.; Hanson, A. L.; Jones, K. W.

1990-04-01

Spatial distributions and concentrations of trace elements (TE) in the brain are important because TE perform catalytic and structural functions in enzymes which regulate brain function and development. We have investigated the distributions of TE in rat cerebellum. Structures were sectioned and analyzed by the Synchrotron Radiation Induced X-ray Emission (SRIXE) method using the NSLS X-26 white-light microprobe facility. Advantages important for TE analysis of biological specimens with X-ray microscopy include short time of measurement, high brightness and flux, good spatial resolution, multielemental detection, good sensitivity, and nondestructive irradiation. Trace elements were measured in thin rat brain sections of 20 μm thickness. The analyses were performed on sample volumes as small as 0.2 nl with Minimum Detectable Limits (MDL) of 50 ppb wet weight for Fe, 100 ppb wet weight for Cu, and Zn, and 1 ppm wet weight for Pb. The distribution of TE in the molecular cell layer, granule cell layer and fiber tract of rat cerebella was investigated. Both point analyses and two-dimensional semiquantitative mapping of the TE distribution in a section were used. All analyzed elements were observed in each structure of the cerebellum except mercury which was not observed in granule cell layer or fiber tract. This approach permits an exacting correlation of the TE distribution in complex structure with the diet, toxic elements, and functional status of the animal.

Dancing in the Dark: New Brown Dwarf Binaries from Kernel Phase Interferometry

NASA Astrophysics Data System (ADS)

Pope, Benjamin; Martinache, Frantz; Tuthill, Peter

2013-04-01

This paper revisits a sample of ultracool dwarfs in the solar neighborhood previously observed with the Hubble Space Telescope's NICMOS NIC1 instrument. We have applied a novel high angular resolution data analysis technique based on the extraction and fitting of kernel phases to archival data. This was found to deliver a dramatic improvement over earlier analysis methods, permitting a search for companions down to projected separations of ~1 AU on NIC1 snapshot images. We reveal five new close binary candidates and present revised astrometry on previously known binaries, all of which were recovered with the technique. The new candidate binaries have sufficiently close separation to determine dynamical masses in a short-term observing campaign. We also present four marginal detections of objects which may be very close binaries or high-contrast companions. Including only confident detections within 19 pc, we report a binary fraction of at least \\epsilon _b = 17.2^{+5.7}_{-3.7} %. The results reported here provide new insights into the population of nearby ultracool binaries, while also offering an incisive case study of the benefits conferred by the kernel phase approach in the recovery of companions within a few resolution elements of the point-spread function core. Based on observations performed with the NASA/ESA Hubble Space Telescope. The Hubble observations are associated with proposal ID 10143 and 10879 and were obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS 5-26555.

Kepler-424 b: A 'lonely' hot Jupiter that found A companion

DOE Office of Scientific and Technical Information (OSTI.GOV)

Endl, Michael; Caldwell, Douglas A.; Barclay, Thomas

Hot Jupiter systems provide unique observational constraints for migration models in multiple systems and binaries. We report on the discovery of the Kepler-424 (KOI-214) two-planet system, which consists of a transiting hot Jupiter (Kepler-424b) in a 3.31 day orbit accompanied by a more massive outer companion in an eccentric (e = 0.3) 223 day orbit. The outer giant planet, Kepler-424c, is not detected transiting the host star. The masses of both planets and the orbital parameters for the second planet were determined using precise radial velocity (RV) measurements from the Hobby-Eberly Telescope (HET) and its High Resolution Spectrograph (HRS). Inmore » stark contrast to smaller planets, hot Jupiters are predominantly found to be lacking any nearby additional planets; they appear to be {sup l}onely{sup .} This might be a consequence of these systems having a highly dynamical past. The Kepler-424 planetary system has a hot Jupiter in a multiple system, similar to υ Andromedae. We also present our results for Kepler-422 (KOI-22), Kepler-77 (KOI-127), Kepler-43 (KOI-135), and Kepler-423 (KOI-183). These results are based on spectroscopic data collected with the Nordic Optical Telescope (NOT), the Keck 1 telescope, and HET. For all systems, we rule out false positives based on various follow-up observations, confirming the planetary nature of these companions. We performed a comparison with planetary evolutionary models which indicate that these five hot Jupiters have heavy element contents between 20 and 120 M {sub ⊕}.« less

Regulation of human bone sialoprotein gene transcription by platelet-derived growth factor-BB.

PubMed

Mezawa, Masaru; Araki, Shouta; Takai, Hideki; Sasaki, Yoko; Wang, Shuang; Li, Xinyue; Kim, Dong-Soon; Nakayama, Youhei; Ogata, Yorimasa

2009-04-15

Platelet-derived growth factor (PDGF) is produced by mesenchymal cells and released by platelets following aggregation and is synthesized by osteoblasts. In bone, PDGF stimulates proliferation and differentiation of osteoblasts. PDGF also increases bone resorption, most likely by increasing the number of osteoclasts. Bone sialoprotein (BSP) is thought to function in the initial mineralization of bone, selectively expressed by differentiated osteoblast. To determine the molecular mechanisms PDGF regulation of human BSP gene transcription, we have analyzed the effects of PDGF-BB on osteoblast-like Saos2 and ROS17/2.8 cells. PDGF-BB (5 ng/ml) increased BSP mRNA and protein levels at 12 h in Saos2 cells, and induced BSP mRNA expression at 3 h, reached maximal at 12 h in ROS17/2.8 cells. Transient transfection analyses were performed using chimeric constructs of the human BSP gene promoter linked to a luciferase reporter gene. Treatment of Saos2 cells with PDGF-BB (5 ng/ml, 12 h) increased luciferase activities of all constructs between -184LUC to -2672LUC including the human BSP gene promoter. Effects of PDGF-BB abrogated in constructs included 2 bp mutations in the two cAMP response elements (CRE1 and CRE2), activator protein 1(3) (AP1(3)) and shear stress response element 1 (SSRE1). Luciferase activities induced by PDGF-BB were blocked by protein kinase A inhibitor H89 and tyrosine kinase inhibitor herbimycin A. Gel mobility shift analyses showed that PDGF-BB increased binding of CRE1, CRE2, AP1(3) and SSRE1 elements. CRE1- and CRE2-protein complexes were supershifted by CREB1 and phospho-CREB1 antibodies. Notably, AP1(3)-protein complexes were supershifted by c-Fos and JunD, and disrupted by CREB1, phospho-CREB1, c-Jun and Fra2 antibodies. These studies, therefore, demonstrate that PDGF-BB stimulates human BSP transcription by targeting the CRE1, CRE2, AP1(3) and SSRE1 elements in the human BSP gene promoter.

Spectral characterization, thermal and biological activity studies of Schiff base complexes derived from 4,4‧-Methylenedianiline, ethanol amine and benzil

NASA Astrophysics Data System (ADS)

Emam, Sanaa Moustafa

2017-04-01

Some new metal(II) complexes of asymmetric Schiff base ligand were prepared by template technique. The shaped complexes are in binuclear structures and were explained through elemental analysis, molar conductivity, various spectroscopic methods (IR, U.V-Vis, XRD, ESR), thermal (TG) and magnetic moment measurements. The IR spectra were done demonstrating that the Schiff base ligand acts as neutral tetradentate moiety in all metal complexes. The electronic absorption spectra represented octahedral geometry for all complexes, while, the ESR spectra for Cu(II) complex showed axially symmetric g-tensor parameter with g׀׀ > g⊥ > 2.0023 indicating to 2B1g ground state with (dx2-y2)1 configuration. The nature of the solid residue created from TG estimations was affirmed utilizing IR and XRD spectra. The biological activity of the prepared complexes was studied against Land Snails. Additionally, the in vitro antitumor activity of the synthesized complexes with Hepatocellular Carcinoma cell (Hep-G2) was examined. It was observed that Zn(II) complex (5), exhibits a high inhibition of growth of the cell line with IC50 of 7.09 μg/mL.

Search for the Missing lncs: Gene Regulatory Networks in Neural Crest Development and Long Non-coding RNA Biomarkers of Hirschsprung's Disease

EPA Science Inventory

Hirschsprung’s disease (HSCR), a birth defect characterized by variable aganglionosis of the gut, affects about 1 in 5000 births, and is a consequence of abnormal development of neural crest cells, from which enteric ganglia derive. In the companion article in this issue (Shen et...

Directions for Space-Based Low-Frequency Radio Astronomy 2. Telescopes

NASA Astrophysics Data System (ADS)

Basart, J. P.; Burns, J. O.; Dennison, B. K.; Weiler, K. W.; Kassim, N. E.; Castillo, S. P.; McCune, B. M.

Astronomical studies of celestial sources at low radio frequencies (0.3 to 30 MHz) lag far behind the investigations of celestial sources at high radio frequencies. In a companion paper [Basart et al., this issue] we discussed the need for low-frequency investigations, and in this paper we discuss the telescopes required to make the observations. Radio telescopes for use in the low-frequency range can be built principally from ``off-the-shelf'' components. For relatively little cost for a space mission, great strides can be made in deploying arrays of antennas and receivers in space that would produce data contributing significantly to our understanding of galaxies and galactic nebulae. In this paper we discuss an evolutionary sequence of telescopes, antenna systems, receivers, and (u,v) plane coverage. The telescopes are space-based because of the disruptive aspects of the Earth's ionosphere on low-frequency celestial signals traveling to the Earth's surface. Orbiting antennas consisting of array elements deposited on a Kevlar balloon have strong advantages of nearly identical multiple beams over 4π steradians and few mechanical aspects in deployment and operation. The relatively narrow beam width of these antennas can significantly help reduce the ``confusion'' problem. The evolutionary sequence of telescopes starts with an Earth-orbiting spectrometer to measure the low-frequency radio environment in space, proceeds to a two-element interferometer, then to an orbiting array, and ends with a telescope on the lunar farside. The sequence is in the order of increasing capability which is also the order of increasing complexity and cost. All the missions can be accomplished with current technology.

A Model for Siderophile Element Distribution in Planetary Differentiation

NASA Technical Reports Server (NTRS)

Humayun, M.; Rushmer, T.; Rankenburg, K.; Brandon, A. D.

2005-01-01

Planetary differentiation begins with partial melting of small planetesimals. At low degrees of partial melting, a sulfur-rich liquid segregates by physical mechanisms including deformation-assisted porous flow. Experimental studies of the physical mechanisms by which Fe-S melts segregate from the silicate matrix of a molten H chondrite are part of a companion paper. Geochemical studies of these experimental products revealed that metallic liquids were in equilibrium with residual metal in the H chondrite matrix. This contribution explores the geochemical signatures produced by early stages of core formation. Particularly, low-degree partial melt segregation of Fe-S liquids leaves residual metal in the silicate matrix. Some achondrites appear to be residues of partial melting, e.g., ureilites, which are known to contain metal. The metal in these achondrites may show a distinct elemental signature. To quantify the effect of sulfur on siderophile element contents of residual metal we have developed a model based on recent parametrizations of equilibrium solid metal-liquid metal partitioning experiments.

Social Work Practitioners and the Human-Companion Animal Bond: A National Study

ERIC Educational Resources Information Center

Risley-Curtiss, Christina

2010-01-01

Extensive research documents powerful relationships between humans and companion animals, and 62 percent of U. S. households report having a companion animal. Social workers are likely to work with individuals and families with companion animals; thus, the inclusion of such animals in both practice and research as a natural extension of social…

45 CFR 2551.121 - What legal limitations apply to the operation of the Senior Companion Program and to the...

Code of Federal Regulations, 2010 CFR

2010-10-01

... the Senior Companion Program and to the expenditure of grant funds? 2551.121 Section 2551.121 Public... SENIOR COMPANION PROGRAM Restrictions and Legal Representation § 2551.121 What legal limitations apply to the operation of the Senior Companion Program and to the expenditure of grant funds? (a) Political...

45 CFR 2551.101 - What rule governs the recruitment and enrollment of persons who do not meet the income...

Code of Federal Regulations, 2010 CFR

2010-10-01

... of persons who do not meet the income eligibility guidelines to serve as Senior Companions without...) CORPORATION FOR NATIONAL AND COMMUNITY SERVICE SENIOR COMPANION PROGRAM Non-Stipended Senior Companions... eligibility guidelines to serve as Senior Companions without stipends? Over-income persons, age 55 or over...

Participative Evaluation and the Quality of Community Empowerment Training of "Program Keluarga Harapan" (PKH) Companions

ERIC Educational Resources Information Center

Rasyad, Ach.

2016-01-01

This research is aiming at describing: (1) the implementation of community empowerment training of PKH companions, (2) types of participative evaluation used in the PKH companion training, and (3) obstacles and supporting factors in PKH companion training using the participative evaluation. The study employed qualitative approach with case study…

Scale relativity theory and integrative systems biology: 1. Founding principles and scale laws.

PubMed

Auffray, Charles; Nottale, Laurent

2008-05-01

In these two companion papers, we provide an overview and a brief history of the multiple roots, current developments and recent advances of integrative systems biology and identify multiscale integration as its grand challenge. Then we introduce the fundamental principles and the successive steps that have been followed in the construction of the scale relativity theory, and discuss how scale laws of increasing complexity can be used to model and understand the behaviour of complex biological systems. In scale relativity theory, the geometry of space is considered to be continuous but non-differentiable, therefore fractal (i.e., explicitly scale-dependent). One writes the equations of motion in such a space as geodesics equations, under the constraint of the principle of relativity of all scales in nature. To this purpose, covariant derivatives are constructed that implement the various effects of the non-differentiable and fractal geometry. In this first review paper, the scale laws that describe the new dependence on resolutions of physical quantities are obtained as solutions of differential equations acting in the scale space. This leads to several possible levels of description for these laws, from the simplest scale invariant laws to generalized laws with variable fractal dimensions. Initial applications of these laws to the study of species evolution, embryogenesis and cell confinement are discussed.

Companion Animals, Natural Disasters and the Law: An Australian Perspective.

PubMed

White, Steven

2012-08-27

This article examines the regulation of companion animal welfare during disasters, with some context provided by two recent major disaster events in Australia. Important general lessons for improved disaster management were identified in subsequent inquiries. However, the interests of companion animals continue to be inadequately addressed. This is because key assumptions underpinning disaster planning for companion animals-the primacy of human interests over animal interests and that individuals will properly address companion animal needs during times of disaster-are open to question. In particular these assumptions fail to recognise the inherent value of companion animals, underestimate the strong bond shared by some owners and their animals and, at the same time, overestimate the capacity of some owners to adequately meet the needs of their animals.

Evaluating Checklist Use in Companion Animal Wellness Visits in a Veterinary Teaching Hospital: A Preliminary Study.

PubMed

Nappier, Michael T; Corrigan, Virginia K; Bartl-Wilson, Lara E; Freeman, Mark; Werre, Stephen; Tempel, Eric

2017-01-01

The number of companion animal wellness visits in private practice has been decreasing, and one important factor cited is the lack of effective communication between veterinarians and pet owners regarding the importance of preventive care. Checklists have been widely used in many fields and are especially useful in areas where a complex task must be completed with multiple small steps, or when cognitive fatigue is evident. The use of checklists in veterinary medical education has not yet been thoroughly evaluated as a potential strategy to improve communication with pet owners regarding preventive care. The authors explored whether the use of a checklist based on the American Animal Hospital Association/American Veterinary Medical Association canine and feline preventive care guidelines would benefit senior veterinary students in accomplishing more complete canine and feline wellness visits. A group of students using provided checklists was compared to a control group of students who did not use checklists on the basis of their medical record notes from the visits. The students using the checklists were routinely more complete in several areas of a wellness visit vs. those who did not use the checklists. However, neither group of students routinely discussed follow-up care recommendations such as frequency or timing of follow-up visits. The study authors recommend considering checklist use for teaching and implementing wellness in companion animal primary care veterinary clinical teaching settings.

SU-8 based microdevices to study self-induced chemotaxis in 3D microenvironments

NASA Astrophysics Data System (ADS)

Ayuso, Jose; Monge, Rosa; Llamazares, Guillermo; Moreno, Marco; Agirregabiria, Maria; Berganzo, Javier; Doblaré, Manuel; Ochoa, Iñaki; Fernandez, Luis

2015-05-01

Tissues are complex three-dimensional structures in which cell behaviour is frequently guided by chemotactic signals. Although starvation and nutrient restriction induce many different chemotactic processes, the recreation of such conditions in vitro remains difficult when using standard cell culture equipment. Recently, microfluidic techniques have arisen as powerful tools to mimic such physiological conditions. In this context, microfluidic three-dimensional cell culture systems require precise control of cell/hydrogel location because samples need to be placed within a microchamber without obstruction of surrounding elements. In this article, SU-8 is studied as structural material for the fabrication of complex cell culture devices due to its good mechanical properties, low gas permeability and sensor integration capacity. In particular, this manuscript presents a SU-8 based microdevice designed to create “self-induced” medium starvation, based on the combination of nutrient restriction and natural cell metabolism. Results show a natural migratory response towards nutrient source, showing how cells adapt to their own microenvironment modifications. The presented results demonstrate the SU-8 potential for microdevice fabrication applied to cell culture.

Cis-acting elements in the promoter region of the human aldolase C gene.

PubMed

Buono, P; de Conciliis, L; Olivetta, E; Izzo, P; Salvatore, F

1993-08-16

We investigated the cis-acting sequences involved in the expression of the human aldolase C gene by transient transfections into human neuroblastoma cells (SKNBE). We demonstrate that 420 bp of the 5'-flanking DNA direct at high efficiency the transcription of the CAT reporter gene. A deletion between -420 bp and -164 bp causes a 60% decrease of CAT activity. Gel shift and DNase I footprinting analyses revealed four protected elements: A, B, C and D. Competition analyses indicate that Sp1 or factors sharing a similar sequence specificity bind to elements A and B, but not to elements C and D. Sequence analysis shows a half palindromic ERE motif (GGTCA), in elements B and D. Region D binds a transactivating factor which appears also essential to stabilize the initiation complex.

Palladium(II) complexes with R(2)edda derived ligands. Part IV. O,O'-dialkyl esters of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid dihydrochloride and their palladium(II) complexes: synthesis, characterization and in vitro antitumoral activity against chronic lymphocytic leukemia (CLL) cells.

PubMed

Vujić, Jelena M; Cvijović, Milica; Kaluderović, Goran N; Milovanović, Marija; Zmejkovski, Bojana B; Volarević, Vladislav; Arsenijević, Nebojsa; Sabo, Tibor J; Trifunović, Srećko R

2010-09-01

Four novel bidentate N,N'-ligand precursors, including O,O'-dialkyl esters (alkyl = ethyl, n-propyl, n-butyl and n-pentyl), L1 x 2 HCl-L4 x 2 HCl, of (S,S)-ethylenediamine-N,N'-di-2-(4-methyl)-pentanoic acid dihydrochloride [(S,S)-H(4)eddl]Cl(2) and the corresponding palladium(II) complexes 1-4, were prepared and characterized by IR, (1)H NMR and (13)C NMR spectroscopy and elemental analysis. In vitro cytotoxicity of all compounds was determined against chronic lymphocytic leukemia cells (CLL). The compounds were found to exhibit higher antitumoral activity than cisplatin. The most active compound 2, [PdCl(2){(S,S)-nPr(2)eddl}], was found to be 13.6 times more active than cisplatin on CLL cells. 2010 Elsevier Masson SAS. All rights reserved.

Modeling Endoplasmic Reticulum Network Maintenance in a Plant Cell.

PubMed

Lin, Congping; White, Rhiannon R; Sparkes, Imogen; Ashwin, Peter

2017-07-11

The endoplasmic reticulum (ER) in plant cells forms a highly dynamic network of complex geometry. ER network morphology and dynamics are influenced by a number of biophysical processes, including filament/tubule tension, viscous forces, Brownian diffusion, and interactions with many other organelles and cytoskeletal elements. Previous studies have indicated that ER networks can be thought of as constrained minimal-length networks acted on by a variety of forces that perturb and/or remodel the network. Here, we study two specific biophysical processes involved in remodeling. One is the dynamic relaxation process involving a combination of tubule tension and viscous forces. The other is the rapid creation of cross-connection tubules by direct or indirect interactions with cytoskeletal elements. These processes are able to remodel the ER network: the first reduces network length and complexity whereas the second increases both. Using live cell imaging of ER network dynamics in tobacco leaf epidermal cells, we examine these processes on ER network dynamics. Away from regions of cytoplasmic streaming, we suggest that the dynamic network structure is a balance between the two processes, and we build an integrative model of the two processes for network remodeling. This model produces quantitatively similar ER networks to those observed in experiments. We use the model to explore the effect of parameter variation on statistical properties of the ER network. Copyright © 2017 Biophysical Society. Published by Elsevier Inc. All rights reserved.

Cross-linking of surface Ig receptors on murine B lymphocytes stimulates the expression of nuclear tetradecanoyl phorbol acetate-response element-binding proteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiles, T.C.; Liu, J.L.; Rothstein, T.L.

1991-03-15

Cross-linking of sIg on primary B lymphocytes leads to increased nuclear DNA-binding activity specific for the tetradecanoyl phorbol acetate-response element (TRE), as judged by gel mobility shift assays. Stimulation of B cells to enter S phase of the cell cycle by treatment with the combination of phorbol ester plus calcium ionophore also stimulated nuclear TRE-binding activity within 2 h, with maximal expression at 4 h; however, phorbol ester and calcium ionophore were not as effective in stimulating binding activity when examined separately. Stimulated nuclear expression of TRE-binding activity appears to require protein synthesis. Fos- and Jun/AP-1-related proteins participate directly inmore » the identified nucleoprotein complex, as shown by the ability of c-fos- and c-jun-specific antisera to either alter or completely abolish electrophoretic migration of the complex in native gels. Further, UV photo-cross-linking studies identified two major TRE-binding protein species, whose sizes correspond to TRE-binding proteins derived from HeLa cell nuclear extracts. The results suggest that in primary B cells nuclear TRE-binding activity represents a downstream signaling event that occurs subsequent to changes in protein kinase C activity and intracellular Ca2+ but that can be triggered physiologically through sIg.« less

A finite volume method for trace element diffusion and partitioning during crystal growth

NASA Astrophysics Data System (ADS)

Hesse, Marc A.

2012-09-01

A finite volume method on a uniform grid is presented to compute the polythermal diffusion and partitioning of a trace element during the growth of a porphyroblast crystal in a uniform matrix and in linear, cylindrical and spherical geometry. The motion of the crystal-matrix interface and the thermal evolution are prescribed functions of time. The motion of the interface is discretized and it advances from one cell boundary to next as the prescribed interface position passes the cell center. The appropriate conditions for the flux across the crystal-matrix interface are derived from discrete mass conservation. Numerical results are benchmarked against steady and transient analytic solutions for isothermal diffusion with partitioning and growth. Two applications illustrate the ability of the model to reproduce observed rare-earth element patterns in garnets (Skora et al., 2006) and water concentration profiles around spherulites in obsidian (Watkins et al., 2009). Simulations with diffusion inside the growing crystal show complex concentration evolutions for trace elements with high diffusion coefficients, such as argon or hydrogen, but demonstrate that rare-earth element concentrations in typical metamorphic garnets are not affected by intracrystalline diffusion.

Synthesis, characterization, and biological evaluation of Schiff base-platinum(II) complexes

NASA Astrophysics Data System (ADS)

Shiju, C.; Arish, D.; Bhuvanesh, N.; Kumaresan, S.

2015-06-01

The platinum complexes of Schiff base ligands derived from 4-aminoantipyrine and a few substituted aldehydes were synthesized and characterized by elemental analysis, mass, 1H NMR, IR, electronic spectra, molar conductance, and powder XRD. The structure of one of the ligands L5 was confirmed by a single crystal XRD analysis. The Schiff base ligand crystallized in the triclinic, space group P-1 with a = 7.032(2) Ǻ, b = 9.479(3) Ǻ, c = 12.425(4) Ǻ, α = 101.636(3)°, β = 99.633(3)°, γ = 94.040(3)°, V = 795.0(4) Ǻ3, Z = 2, F(0 0 0) = 352, Dc = 1.405 mg/m3, μ = 0.099 mm-1, R = 0.0378, and wR = 0.0967. The spectral results show that the Schiff base ligand acts as a bidentate donor coordinating through the azomethine nitrogen and the carbonyl oxygen atoms. The geometrical structures of these complexes are found to be square planar. Antimicrobial studies indicate that these complexes exhibit better activity than the ligand. The anticancer activities of the complexes have also been studied towards human cervical cancer cell line (HeLa), Colon Cancer Cells (HCT116) and Epidermoid Carcinoma Cells (A431) and it was found that the [Pt(L3)Cl2] complex is more active.

Potential virulence and antimicrobial susceptibility of Campylobacter jejuni isolates from food and companion animals.

PubMed

Lee, Michelle K; Billington, Stephen J; Joens, Lynn A

2004-01-01

Infection in humans with Campylobacter jejuni is commonly associated with exposure to food animal fecal material. In this study, we report on the recovery, potential for virulence and antimicrobial resistance levels of C. jejuni isolated from food and companion animals. Three hundred and seventy-eight fecal samples from food and companion animals and surface swabs from beef carcasses were tested for the presence of C. jejuni. C. jejuni was isolated from 13.8% (11/80) of dogs, 5% (1/20) of goats, 28.3% (17/60) of dairy cattle, 0% (0/65) of range cattle, 73.5% (36/49) of feedlot cattle, and 94.7% (18/19) of beef carcasses. Beef cattle from a single Arizona herd showed a considerable increase in fecal shedding of C. jejuni from pasture to feedlot and over time on the feedlot. Forty-two isolates were tested for susceptibility to four antimicrobial agents, each representing a class of antimicrobial drug approved for use in both humans and animals. None of the isolates were found to be resistant to erythromycin or gentamicin, whereas 2.4% of isolates were resistant to ciprofloxacin and 28.6% of isolates were resistant to tetracycline. The presence of virulence traits among the 42 isolates was assessed using in vitro macrophage survival and epithelial cell adherence and invasion assays. Of the isolates examined, 17 were able to survive within macrophages through 72 h at viable counts of >/=10(3)/well and 12 were capable of invading epithelial cells at viable counts of >/=10(3)/well. Data from these studies suggests that many of the isolates recovered from the non-poultry animal sources have the capacity to cause disease if transmitted to humans.

[Morphological pathology of classic Kaposi's sarcoma. Ultrastructural studies and reflections on histogenesis].

PubMed

Holzhausen, H J; Stiller, D; Sachs, M

1988-01-01

Histological and electron-microscopic studies were conducted into biopsy material from cases of what is called the classical type of idiopathic Kaposi's sarcoma without acquired immunodeficiency syndrome. Ultrastructural analysis was conducted, with the view to characterizing a possible progenitor cell from which the angioblastic and fibroblastic elements were likely to originate. The biopsy material had been obtained from two males, aged 86 or 83 years, who had been afflicted with the disease for 18 or 8 years. The nodular lesions were typical of Kaposi's sarcoma and were, histologically, made up of variable mixtures of vascular and spindle cell elements. The angiomatous structures were a capillary meshwork or sinusoidal patterns lined by atypical endothelial cells. The spindle cell areas contained large numbers of slit-like spaces which were without endothelial lining but were stuffed with erythrocytes. Flattened endothelioid cells were recordable from semi-thin-sections of some clefts. Haemosiderin was, typically, deposited in places. Electron microscopically, the endothelial cells of vascular channels exhibited varying amounts of characteristic organelles, such as Weibel-Palade bodies, microfilaments and pinocytotic vesicles as well as basal membranes. Cells with typical endothelial markers, too, were detectable in solid sprouts or in capillary-like differentiations with narrow or small lumina. The spindle cell tumour areas consisted of fibroblastic cells with plenty of rough endoplasmic reticulum and surrounded by material of basal membrane nature. Also visible were solid, sprout-type multilayer cell complexes surrounded by basal membranes which exhibited undifferentiated or primitive cellular forms, endothelioid and pericytic. Transitional forms from these complexes to the above vascular tumours or the spindle-cell formations were detectable. These ultrastructural findings might be interpreted to the effect that an angioblastically determined mesenchymal cell, a so-called endothelioblast, was thinkable and was discussed as the precursor cell of atypical vascular and spindle cell proliferation in Kaposi's sarcoma.

The coactivator CBP stimulates human T-cell lymphotrophic virus type I Tax transactivation in vitro.

PubMed

Kashanchi, F; Duvall, J F; Kwok, R P; Lundblad, J R; Goodman, R H; Brady, J N

1998-12-18

Tax interacts with the cellular cyclic AMP-responsive element binding protein (CREB) and facilitates the binding of the coactivator CREB binding protein (CBP), forming a multimeric complex on the cyclic AMP-responsive element (CRE)-like sites in the human T-cell lymphotrophic virus type I (HTLV-I) promoter. The trimeric complex is believed to recruit additional regulatory proteins to the HTLV-I long terminal repeat, but there has been no direct evidence that CBP is required for Tax-mediated transactivation. We present evidence that Tax and CBP activate transcription from the HTLV-I 21 base pair repeats on naked DNA templates. Transcriptional activation of the HTLV-I sequences required both Tax and CBP and could be mediated by either the N-terminal activation domain of CBP or the full-length protein. Fluorescence polarization binding assays indicated that CBP does not markedly enhance the affinity of Tax for the trimeric complex. Transcription analyses suggest that CBP activates Tax-dependent transcription by promoting transcriptional initiation and reinitiation. The ability of CBP to activate the HTLV-I promoter does not involve the stabilization of Tax binding, but rather depends upon gene activation properties of the co-activator that function in the context of a naked DNA template.

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

The Analysis of a Diet for the Human Being and the Companion Animal using Big Data in 2016

PubMed Central

Kang, Hye Won

2017-01-01

The purpose of this study was to investigate the diet tendencies of human and companion animals using big data analysis. The keyword data of human diet and companion animals' diet were collected from the portal site Naver from January 1, 2016 until December 31, 2016 and collected data were analyzed by simple frequency analysis, N-gram analysis, keyword network analysis and seasonality analysis. In terms of human, the word exercise had the highest frequency through simple frequency analysis, whereas diet menu most frequently appeared in the N-gram analysis. companion animals, the term dog had the highest frequency in simple frequency analysis, whereas diet method was most frequent through N-gram analysis. Keyword network analysis for human indicated 4 groups: diet group, exercise group, commercial diet food group, and commercial diet program group. However, the keyword network analysis for companion animals indicated 3 groups: diet group, exercise group, and professional medical help group. The analysis of seasonality showed that the interest in diet for both human and companion animals increased steadily since February of 2016 and reached its peak in July. In conclusion, diets of human and companion animals showed similar tendencies, particularly having higher preference for dietary control over other methods. The diets of companion animals are determined by the choice of their owners as effective diet method for owners are usually applied to the companion animals. Therefore, it is necessary to have empirical demonstration of whether correlation of obesity between human being and the companion animals exist. PMID:29124046

The Analysis of a Diet for the Human Being and the Companion Animal using Big Data in 2016.

PubMed

Jung, Eun-Jin; Kim, Young-Suk; Choi, Jung-Wa; Kang, Hye Won; Chang, Un-Jae

2017-10-01

The purpose of this study was to investigate the diet tendencies of human and companion animals using big data analysis. The keyword data of human diet and companion animals' diet were collected from the portal site Naver from January 1, 2016 until December 31, 2016 and collected data were analyzed by simple frequency analysis, N-gram analysis, keyword network analysis and seasonality analysis. In terms of human, the word exercise had the highest frequency through simple frequency analysis, whereas diet menu most frequently appeared in the N-gram analysis. companion animals, the term dog had the highest frequency in simple frequency analysis, whereas diet method was most frequent through N-gram analysis. Keyword network analysis for human indicated 4 groups: diet group, exercise group, commercial diet food group, and commercial diet program group. However, the keyword network analysis for companion animals indicated 3 groups: diet group, exercise group, and professional medical help group. The analysis of seasonality showed that the interest in diet for both human and companion animals increased steadily since February of 2016 and reached its peak in July. In conclusion, diets of human and companion animals showed similar tendencies, particularly having higher preference for dietary control over other methods. The diets of companion animals are determined by the choice of their owners as effective diet method for owners are usually applied to the companion animals. Therefore, it is necessary to have empirical demonstration of whether correlation of obesity between human being and the companion animals exist.

Efficient Recreation of t(11;22) EWSR1-FLI1+ in Human Stem Cells Using CRISPR/Cas9.

PubMed

Torres-Ruiz, Raul; Martinez-Lage, Marta; Martin, Maria C; Garcia, Aida; Bueno, Clara; Castaño, Julio; Ramirez, Juan C; Menendez, Pablo; Cigudosa, Juan C; Rodriguez-Perales, Sandra

2017-05-09

Efficient methodologies for recreating cancer-associated chromosome translocations are in high demand as tools for investigating how such events initiate cancer. The CRISPR/Cas9 system has been used to reconstruct the genetics of these complex rearrangements at native loci while maintaining the architecture and regulatory elements. However, the CRISPR system remains inefficient in human stem cells. Here, we compared three strategies aimed at enhancing the efficiency of the CRISPR-mediated t(11;22) translocation in human stem cells, including mesenchymal and induced pluripotent stem cells: (1) using end-joining DNA processing factors involved in repair mechanisms, or (2) ssODNs to guide the ligation of the double-strand break ends generated by CRISPR/Cas9; and (3) all-in-one plasmid or ribonucleoprotein complex-based approaches. We report that the generation of targeted t(11;22) is significantly increased by using a combination of ribonucleoprotein complexes and ssODNs. The CRISPR/Cas9-mediated generation of targeted t(11;22) in human stem cells opens up new avenues in modeling Ewing sarcoma. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Imaginary Companions: Pretending They Are Real but Knowing They Are Not

ERIC Educational Resources Information Center

Taylor, Marjorie; Mottweiler, Candice M.

2008-01-01

Parents and child specialists are o?ften concerned about the role imaginary companions play in children's lives. Recent research shows that the creation of an imaginary companion is a common and healthy type of pretend play. There are many di?fferent kinds of imaginary companions, including those based on various types of props as well those that…

The Creative Use of Companion Values in Environmental Education and Education for Sustainable Development: Exploring the Educative Moment

ERIC Educational Resources Information Center

Garrison, Jim; Östman, Leif; Håkansson, Michael

2015-01-01

Our paper addresses the emergence and evolution of values in educational settings. It builds upon and extends earlier work on companion meanings to develop a theory of the creative use of companion values and meanings in education. The recognition of companion values in educational practices highlight epistemological, ethical, and aesthetic…

Cost Implications of Value-Based Pricing for Companion Diagnostic Tests in Precision Medicine.

PubMed

Zaric, Gregory S

2016-07-01

Many interpretations of personalized medicine, also referred to as precision medicine, include discussions of companion diagnostic tests that allow drugs to be targeted to those individuals who are most likely to benefit or that allow treatment to be designed in a way such that individuals who are unlikely to benefit do not receive treatment. Many authors have commented on the clinical and competitive implications of companion diagnostics, but there has been relatively little formal analysis of the cost implications of companion diagnostics, although cost reduction is often cited as a significant benefit of precision medicine. We investigate the potential impact on costs of precision medicine implemented through the use of companion diagnostics. We develop a framework in which the costs of companion diagnostic tests are determined by considerations of profit maximization and cost effectiveness. We analyze four scenarios that are defined by the incremental cost-effectiveness ratio of the new drug in the absence of a companion diagnostic test. We find that, in most scenarios, precision medicine strategies based on companion diagnostics should be expected to lead to increases in costs in the short term and that costs would fall only in a limited number of situations.

A Search for a Surviving White Dwarf Companion in SN 1006

NASA Astrophysics Data System (ADS)

Kerzendorf, W. E.; Strampelli, G.; Shen, K. J.; Schwab, J.; Pakmor, R.; Do, T.; Buchner, J.; Rest, A.

2018-05-01

Multiple channels have been proposed to produce Type Ia supernovae, with many scenarios suggesting that the exploding white dwarf accretes from a binary companion pre-explosion. In almost all cases, theory suggests that this companion will survive. However, no such companion has been unambiguously identified in ancient supernova remnants - possibly falsifying the accretion scenario. Existing surveys, however, have only looked for stars as faint as ≈0.1L⊙ and thus might have missed a surviving white dwarf companion. In this work, we present very deep DECAM imaging (u, g, r, z) of the Type Ia supernova remnant SN 1006 specifically to search for a potential surviving white dwarf companion. We find no object that is consistent with a relatively young cooling white dwarf within the inner half of the SN 1006 remnant. We find that if there is a companion white dwarf, it must be redder than the standard white dwarf cooling track, or it must have formed long ago and cooled undisturbed for >108 yr. We conclude that our findings are consistent with the complete destruction of the secondary (such as in a merger) or an anomalously red or very dim surviving companion white dwarf.

Chinese children's imaginary companions: Relations with peer relationships and social competence.

PubMed

Lin, Qiyi; Fu, Hong; Wan, Yingjia; Zhou, Nan; Xu, Hui

2016-09-25

We investigated relationships between Chinese children's imaginary companions (ICs) and peer relationships and social competence in 160 children, aged 5-6 years old. Children and their mothers participated in the interviews regarding the details of the children's ICs, including the type of the companion and the quality of the child-IC relationship. Peer relationships were assessed using sociometric nomination and perceived popularity nomination. Teachers rated children's social competence. Here, 55 children (34.3%) were deemed to have engaged in imaginary companion play. There was no relationship between imaginary companion types and child-IC relationship qualities. Children with invisible friends received more positive nominations than children with personified objects. Children with egalitarian relationships received more positive nominations and popularity nominations, but fewer negative nominations and unpopularity nominations than children with hierarchical relationships. Compared with children with hierarchical relationships, teachers rated the children with egalitarian relationships higher in social competence. The results suggest that imaginary companion types and relationship qualities may represent different dimensions of imaginary companions, calling attentions to the different mechanisms underlying imaginary companion types and relationship qualities with respect to social functioning. © 2016 International Union of Psychological Science.

OGLE-2016-BLG-0263Lb: Microlensing Detection of a Very Low-mass Binary Companion through a Repeating Event Channel

NASA Astrophysics Data System (ADS)

Han, C.; Udalski, A.; Gould, A.; Bond, I. A.; and; Albrow, M. D.; Chung, S.-J.; Jung, Y. K.; Ryu, Y.-H.; Shin, I.-G.; Yee, J. C.; Zhu, W.; Cha, S.-M.; Kim, S.-L.; Kim, D.-J.; Lee, C.-U.; Lee, Y.; Park, B.-G.; KMTNet Collaboration; Skowron, J.; Mróz, P.; Pietrukowicz, P.; Kozłowski, S.; Poleski, R.; Szymański, M. K.; Soszyński, I.; Ulaczyk, K.; Pawlak, M.; OGLE Collaboration; Abe, F.; Asakura, Y.; Barry, R.; Bennett, D. P.; Bhattacharya, A.; Donachie, M.; Evans, P.; Fukui, A.; Hirao, Y.; Itow, Y.; Koshimoto, N.; Li, M. C. A.; Ling, C. H.; Masuda, K.; Matsubara, Y.; Muraki, Y.; Nagakane, M.; Ohnishi, K.; Ranc, C.; Rattenbury, N. J.; Saito, To.; Sharan, A.; Sullivan, D. J.; Sumi, T.; Suzuki, D.; Tristram, P. J.; Yamada, T.; Yamada, T.; Yonehara, A.; The MOA Collaboration

2017-10-01

We report the discovery of a planet-mass companion to the microlens OGLE-2016-BLG-0263L. Unlike most low-mass companions that were detected through perturbations to the smooth and symmetric light curves produced by the primary, the companion was discovered through the channel of a repeating event, in which the companion itself produced its own single-mass light curve after the event produced by the primary had ended. Thanks to the continuous coverage of the second peak by high-cadence surveys, the possibility of the repeating nature due to source binarity is excluded with a 96% confidence level. The mass of the companion estimated by a Bayesian analysis is {M}{{p}}={4.1}-2.5+6.5 {M}{{J}}. The projected primary-companion separation is {a}\\perp ={6.5}-1.9+1.3 au. The ratio of the separation to the snow-line distance of {a}\\perp /{a}{sl}˜ 15.4 corresponds to the region beyond Neptune, the outermost planet of the solar system. We discuss the importance of high-cadence surveys in expanding the range of microlensing detections of low-mass companions and future space-based microlensing surveys.

Companion Animals, Natural Disasters and the Law: An Australian Perspective

PubMed Central

White, Steven

2012-01-01

Simple Summary One of the issues raised by recent natural disasters in Australia is the management of companion animal welfare in disaster planning, response and recovery. Official inquiries following these disasters uncovered a number of shortcomings in addressing the management of animal welfare issues. This article suggests that despite some reform following these events, disaster management still fails to take seriously the interests of companion animals. Abstract This article examines the regulation of companion animal welfare during disasters, with some context provided by two recent major disaster events in Australia. Important general lessons for improved disaster management were identified in subsequent inquiries. However, the interests of companion animals continue to be inadequately addressed. This is because key assumptions underpinning disaster planning for companion animals—the primacy of human interests over animal interests and that individuals will properly address companion animal needs during times of disaster—are open to question. In particular these assumptions fail to recognise the inherent value of companion animals, underestimate the strong bond shared by some owners and their animals and, at the same time, overestimate the capacity of some owners to adequately meet the needs of their animals. PMID:26487028

Intermolecular Interactions of Homologs of Germ Plasm Components in Mammalian Germ Cells

PubMed Central

Fox, Mark S.; Clark, Amander T.; El Majdoubi, Mohammed; Vigne, Jean-Louis; Urano, Jun; Hostetler, Chris E.; Griswold, Michael D.; Weiner, Richard I.; Pera, Renee A. Reijo

2007-01-01

In some species such as flies, worms, frogs, and fish the key to forming and maintaining early germ cell populations is the assembly of germ plasm, microscopically-distinct egg cytoplasm that is rich in RNAs, RNA-binding proteins and ribosomes. Cells which inherit germ plasm are destined for the germ cell lineage. In contrast, in mammals, germ cells are formed and maintained later in development as a result of inductive signaling from one embryonic cell type to another. Research advances, using complementary approaches, including identification of key signaling factors that act during the initial stages of germ cell development, differentiation of germ cells in vitro from mouse and human embryonic stem cells and the demonstration, that homologs of germ plasm components are conserved in mammals, have shed light on key elements in the early development of mammalian germ cells. Here, we use FRET (Fluorescence Resonance Energy Transfer) to demonstrate that living mammalian germ cells possess specific RNA/protein complexes that contain germ plasm homologs, beginning in the earliest stages of development examined. Moreover, we demonstrate that although both human and mouse germ cells and embryonic stem cells express the same proteins, germ cell specific protein/protein interactions distinguish germ cells from precursor embryonic stem cells in vitro; interactions also determine sub-cellular localization of complex components. Finally, we suggest that assembly of similar protein complexes may be central to differentiation of diverse cell lineages and provide useful diagnostic tools for isolation of specific cell types from the assorted types differentiated from embryonic stem cells. PMID:16996493

Controlling the strontium-doping in calcium phosphate microcapsules through yeast-regulated biomimetic mineralization.

PubMed

Huang, Miaojun; Li, Tianjie; Pan, Ting; Zhao, Naru; Yao, Yongchang; Zhai, Zhichen; Zhou, Jiaan; Du, Chang; Wang, Yingjun

2016-10-01

Yeast cells have controllable biosorption on metallic ions during metabolism. However, few studies were dedicated to using yeast-regulated biomimetic mineralization process to control the strontium-doped positions in calcium phosphate microcapsules. In this study, the yeast cells were allowed to pre-adsorb strontium ions metabolically and then served as sacrificing template for the precipitation and calcination of mineral shell. The pre-adsorption enabled the microorganism to enrich of strontium ions into the inner part of the microcapsules, which ensured a slow-release profile of the trace element from the microcapsule. The co-culture with human marrow stromal cells showed that gene expressions of alkaline phosphatase and Collagen-I were promoted. The promotion of osteogenic differentiation was further confirmed in the 3D culture of cell-material complexes. The strategy using living microorganism as 'smart doping apparatus' to control incorporation of trace element into calcium phosphate paved a pathway to new functional materials for hard tissue regeneration.

HYAL-2–WWOX–SMAD4 Signaling in Cell Death and Anticancer Response

PubMed Central

Hsu, Li-Jin; Chiang, Ming-Fu; Sze, Chun-I; Su, Wan-Pei; Yap, Ye Vone; Lee, I-Ting; Kuo, Hsiang-Ling; Chang, Nan-Shan

2016-01-01

Hyaluronidase HYAL-2 is a membrane-anchored protein and also localizes, in part, in the lysosome. Recent study from animal models revealed that both HYAL-1 and HYAL-2 are essential for the metabolism of hyaluronan (HA). Hyal-2 deficiency is associated with chronic thrombotic microangiopathy with hemolytic anemia in mice due to over accumulation of high molecular size HA. HYAL-2 is essential for platelet generation. Membrane HYAL-2 degrades HA bound by co-receptor CD44. Also, in a non-canonical signal pathway, HYAL-2 serves as a receptor for transforming growth factor beta (TGF-β) to signal with downstream tumor suppressors WWOX and SMAD4 to control gene transcription. When SMAD4 responsive element is overly driven by the HYAL-2–WWOX–SMAD4 signaling complex, cell death occurs. When rats are subjected to traumatic brain injury, over accumulation of a HYAL-2–WWOX complex occurs in the nucleus to cause neuronal death. HA induces the signaling of HYAL-2–WWOX–SMAD4 and relocation of the signaling complex to the nucleus. If the signaling complex is overexpressed, bubbling cell death occurs in WWOX-expressing cells. In addition, a small synthetic peptide Zfra (zinc finger-like protein that regulates apoptosis) binds membrane HYAL-2 of non-T/non-B spleen HYAL-2+ CD3− CD19− Z lymphocytes and activates the cells to generate memory anticancer response against many types of cancer cells in vivo. Whether the HYAL-2–WWOX–SMAD4 signaling complex is involved is discussed. In this review and opinion article, we have updated the current knowledge of HA, HYAL-2 and WWOX, HYAL-2–WWOX–SMAD4 signaling, bubbling cell death, and Z cell activation for memory anticancer response. PMID:27999774

Intersection of transfer cells with phloem biology—broad evolutionary trends, function, and induction

PubMed Central

Andriunas, Felicity A.; Zhang, Hui-Ming; Xia, Xue; Patrick, John W.; Offler, Christina E.

2013-01-01

Transfer cells (TCs) are ubiquitous throughout the plant kingdom. Their unique ingrowth wall labyrinths, supporting a plasma membrane enriched in transporter proteins, provides these cells with an enhanced membrane transport capacity for resources. In certain plant species, TCs have been shown to function to facilitate phloem loading and/or unloading at cellular sites of intense resource exchange between symplasmic/apoplasmic compartments. Within the phloem, the key cellular locations of TCs are leaf minor veins of collection phloem and stem nodes of transport phloem. In these locations, companion and phloem parenchyma cells trans-differentiate to a TC morphology consistent with facilitating loading and re-distribution of resources, respectively. At a species level, occurrence of TCs is significantly higher in transport than in collection phloem. TCs are absent from release phloem, but occur within post-sieve element unloading pathways and particularly at interfaces between generations of developing Angiosperm seeds. Experimental accessibility of seed TCs has provided opportunities to investigate their inductive signaling, regulation of ingrowth wall formation and membrane transport function. This review uses this information base to explore current knowledge of phloem transport function and inductive signaling for phloem-associated TCs. The functional role of collection phloem and seed TCs is supported by definitive evidence, but no such information is available for stem node TCs that present an almost intractable experimental challenge. There is an emerging understanding of inductive signals and signaling pathways responsible for initiating trans-differentiation to a TC morphology in developing seeds. However, scant information is available to comment on a potential role for inductive signals (auxin, ethylene and reactive oxygen species) that induce seed TCs, in regulating induction of phloem-associated TCs. Biotic phloem invaders have been used as a model to speculate on involvement of these signals. PMID:23847631

New Clues to the Mysterious Origin of Wide-Separation Planetary-Mass Companions

NASA Astrophysics Data System (ADS)

Bryan, Marta

2018-01-01

Over the past decade, direct imaging searches for young gas giant planets have revealed a new population of young planetary-mass companions with extremely wide orbital separations (>50 AU) and masses near or at the deuterium-burning limit. These companions pose significant challenges to standard formation models, including core accretion, disk instability, and turbulent fragmentation. In my talk I will discuss new results from high-contrast imaging and high-resolution infrared spectroscopy of a sample of directly imaged wide-separation companions that can be used to directly test these three competing formation mechanisms. First, I use high-contrast imaging to strongly discount scattering as a hypothesis for the origin of wide-separation companions. Second, I measure rotation rates of a subset of these companions using their near-IR spectra, and place the first constraints on the angular momentum evolution of young planetary-mass objects. Finally, I explore the ability of high-resolution spectroscopy to constrain the atmospheric C/O ratios of these companions, providing a complementary test of competing formation scenarios.

HUNTING THE COOLEST DWARFS: METHODS AND EARLY RESULTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Schneider, A.; Song, Inseok; Melis, Carl

2011-12-20

We present the methods and first results of a survey of nearby high proper motion main-sequence stars to probe for cool companions with the Gemini camera at Lick Observatory. This survey uses a sample of old (age > 2 Gyr) stars as targets to probe for companions down to temperatures of 500 K. Multi-epoch observations allow us to discriminate comoving companions from background objects. So far, our survey has successfully rediscovered the wide T8.5 companion to GJ 1263 and has discovered a companion to the nearby M0V star GJ 660.1. The companion to GJ 660.1 (GJ 660.1B) is {approx}4 magmore » fainter than its host star in the J-band and is located at a projected separation of {approx}120 AU. Known trigonometric parallax and Two Micron All Sky Survey magnitudes for the GJ 660.1 system indicate a spectral type for the companion of M9 {+-} 2.« less

A HST/WFC3 Search for Substellar Companions in the Orion Nebula Cluster

NASA Astrophysics Data System (ADS)

Strampelli, Giovanni Maria; Aguilar, Jonathan; Aparicio, Antonio; Piotto, Giampaolo; Pueyo, Laurent; Robberto, Massimo

2018-01-01

We present new results relative to the population of substellar binaries in the Orion Nebula Cluster. We reprocessed HST/WFC3 data using an analysis technique developed to detect close companions in the wings of the stellar PSFs, based on the PyKLIP implementation of the KLIP PSF subtraction algorithm. Starting from a sample of ~1200 stars selected over the range J=11-15 mag, we were able to uncover ~80 candidate companions in the magnitude range J=16-23 mag. We use the presence of the 1.4 micron H2O absorption feature in the companion photosphere to discriminate 32 bona-fide substellar candidates from a population of reddened background objects. We derive an estimate of the companion mass assuming a 2Myr isochrone and the reddening of their primary. With 8 stellar companions, 19 brown dwarfs and 5 planetary mass objects, our study provide us with an unbiased sample of companions at the low-mass end of the IMF, probing the transition from binary to planetary systems.

Optimization and comparative analysis of plant organellar DNA enrichment methods suitable for next generation sequencing

USDA-ARS?s Scientific Manuscript database

Plant organellar genomes contain large repetitive elements that may undergo pairing or recombination to form complex structures and/or sub-genomic fragments. Organellar genomes also exist in admixtures within a given cell or tissue type (heteroplasmy) and abundance of sub-types may change through de...

Synthesis, characterization and in vitro anticancer activity of 18-membered octaazamacrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II)

NASA Astrophysics Data System (ADS)

Kareem, Abdul; Zafar, Hina; Sherwani, Asif; Mohammad, Owais; Khan, Tahir Ali

2014-10-01

An effective series of 18 membered octaazamacrocyclic complexes of the type [MLX2], where X = Cl or NO3 have been synthesized by template condensation reaction of oxalyl dihydrazide with dibenzoylmethane and metal salt in 2:2:1 molar ratio. The formation of macrocyclic framework, stereochemistry and their overall geometry have been characterized by various physico-chemical studies viz., elemental analysis, electron spray ionization-mass spectrometry (ESI-MS), I.R, UV-Vis, 1H NMR, 13C NMR spectroscopy, X-ray diffraction (XRD) and TGA/DTA studies. These studies suggest formation of octahedral macrocyclic complexes of Co(II), Ni(II), Cd(II) and Sn(II). The molar conductance values suggest nonelectrolytic nature for all the complexes. Thermogravimatric analysis shows that all the complexes are stable up to 600 °C. All these complexes have been tested against different human cancer cell lines i.e. human hepatocellular carcinoma (Hep3B), human cervical carcinoma (HeLa), human breast adenocarcinoma (MCF7) and normal cells (PBMC). The newly synthesized 18-membered octaazamacrocyclic complexes during in vitro anticancer evaluation, displayed moderate to good cytotoxicity on liver (Hep3B), cervical (HeLa) and breast (MCF7) cancer cell lines, respectively. The most effective anticancer cadmium complex (C34H28N10CdO10) was found to be active with IC50 values, 2.44 ± 1.500, 3.55 ± 1.600 and 4.82 ± 1.400 in micro-molar on liver, cervical and breast cancer cell lines, respectively.

Fracture Mechanical Analysis of Open Cell Ceramic Foams Under Thermal Shock Loading

NASA Astrophysics Data System (ADS)

Settgast, C.; Abendroth, M.; Kuna, M.

2016-11-01

Ceramic foams made by replica techniques containing sharp-edged cavities, which are potential crack initiators and therefore have to be analyzed using fracture mechanical methods. The ceramic foams made of novel carbon bonded alumina are used as filters in metal melt filtration applications, where the filters are exposed to a thermal shock. During the casting process the filters experience a complex thermo-mechanical loading, which is difficult to measure. Modern numerical methods allow the simulation of such complex processes. As a simplified foam structure an open Kelvin cell is used as a representative volume element. A three-dimensional finite element model containing realistic sharp-edged cavities and three-dimensional sub-models along these sharp edges are used to compute the transient temperature, stress and strain fields at the Kelvin foam. The sharp edges are evaluated using fracture mechanical methods like the J-integral technique. The results of this study describe the influence of the pore size, relative density of the ceramic foam, the heat transfer and selected material parameters on the fracture mechanical behaviour.

Modulation of hepatocyte growth factor gene expression by estrogen in mouse ovary.

PubMed

Liu, Y; Lin, L; Zarnegar, R

1994-09-01

Hepatocyte growth factor (HGF) is expressed in a variety of tissues and cell types under normal conditions and in response to various stimuli such as tissue injury. In the present study, we demonstrate that the transcription of the HGF gene is stimulated by estrogen in mouse ovary. A single injection of 17 beta-estradiol results in a dramatic and transient elevation of the levels of mouse HGF mRNA. Sequence analysis has found that two putative estrogen responsive elements (ERE) reside at -872 in the 5'-flanking region and at +511 in the first intron, respectively, of the mouse HGF gene. To test whether these ERE elements are responsible for estrogen induction of HGF gene expression, chimeric plasmids containing variable regions of the 5'-flanking sequence of HGF gene and the coding region for chloramphenicol acetyltransferase (CAT) gene were transiently transfected into both human endometrial carcinoma RL 95-2 cells and mouse fibroblast NIH 3T3 cells to assess hormone responsiveness. Transfection results indicate that the ERE elements of the mouse HGF gene can confer estrogen action to either homologous or heterologous promoters. Nuclear protein extracts either from RL95-2 cells transfected with the estrogen receptor expression vector or from mouse liver bound in vitro to ERE elements specifically, as shown by band shift assay. Therefore, our results demonstrate that the HGF gene is transcriptionally regulated by estrogen in mouse ovary; and such regulation is mediated via a direct interaction of the estrogen receptor complex with cis-acting ERE elements identified in the mouse HGF gene.

Companion Animal Death.

PubMed

Reisbig, Allison M J; Hafen, McArthur; Siqueira Drake, Adryanna A; Girard, Destiny; Breunig, Zachary B

2017-06-01

Human-animal relationships are increasingly incorporated into families as a normal part of family life. Despite this, relationships with animals are often viewed as inferior to human relationships. This becomes problematic during times of loss and grief when members of a grieving companion animal owner's support system do not understand the salience of the relationship with the animal. Veterinary and other helping professionals need basic information about the experience of companion animal loss in order to help support and normalize the experiences of grieving companion animal owners. The present study qualitatively describes human-animal relationships and the subsequent loss and coping experienced by owners of beloved companion animals. Comparison with human and other types of loss and factors unique to companion animal loss are discussed, and practical applications for veterinary and other helping professionals are provided.

Earth Observatory Satellite system definition study. Report no. 3: Design/cost tradeoff studies. Appendix A: EOS program WBS dictionary. Appendix B: EOS mission functional analysis

NASA Technical Reports Server (NTRS)

1974-01-01

The work breakdown structure (WBS) dictionary for the Earth Observatory Satellite (EOS) is defined. The various elements of the EOS program are examined to include the aggregate of hardware, computer software, services, and data required to develop, produce, test, support, and operate the space vehicle and the companion ground data management system. A functional analysis of the EOS mission is developed. The operations for three typical EOS missions, Delta, Titan, and Shuttle launched are considered. The functions were determined for the top program elements, and the mission operations, function 2.0, was expanded to level one functions. Selection of ten level one functions for further analysis to level two and three functions were based on concern for the EOS operations and associated interfaces.

Design of copper DNA intercalators with leishmanicidal activity.

PubMed

Navarro, Maribel; Cisneros-Fajardo, Efrén José; Sierralta, Aníbal; Fernández-Mestre, Mercedes; Silva, Pedro; Arrieche, Dwight; Marchán, Edgar

2003-04-01

The complexes [Cu(dppz)(NO(3))]NO(3) (1), [Cu(dppz)(2)(NO(3))]NO(3) (2), [Cu(dpq)(NO(3))]NO(3) (3), and [Cu(dpq)(2)(NO(3))]NO(3) (4) were synthesized and characterized by elemental analysis, FAB-mass spectrometry, EPR, UV, and IR spectroscopies, and molar conductivity. DNA interaction studies showed that intercalation is an important way of interacting with DNA for these complexes. The biological activity of these copper complexes was evaluated on Leishmania braziliensis promastigotes, and the results showed leishmanicidal activity. Preliminary ultrastructural studies with the most active complex (2) at 1 h revealed parasite swelling and binucleated cells. This finding suggests that the leishmanicidal activity of the copper complexes could be associated with their interaction with the parasitic DNA.

Vascularization, high-volume solution flow, and localized roles for enzymes of sucrose metabolism during tumorigenesis by Agrobacterium tumefaciens.

PubMed

Wächter, Rebecca; Langhans, Markus; Aloni, Roni; Götz, Simone; Weilmünster, Anke; Koops, Ariane; Temguia, Leopoldine; Mistrik, Igor; Pavlovkin, Jan; Rascher, Uwe; Schwalm, Katja; Koch, Karen E; Ullrich, Cornelia I

2003-11-01

Vascular differentiation and epidermal disruption are associated with establishment of tumors induced by Agrobacterium tumefaciens. Here, we address the relationship of these processes to the redirection of nutrient-bearing water flow and carbohydrate delivery for tumor growth within the castor bean (Ricinus communis) host. Treatment with aminoethoxyvinyl-glycine showed that vascular differentiation and epidermal disruption were central to ethylene-dependent tumor establishment. CO2 release paralleled tumor growth, but water flow increased dramatically during the first 3 weeks. However, tumor water loss contributed little to water flow to host shoots. Tumor water loss was followed by accumulation of the osmoprotectants, sucrose (Suc) and proline, in the tumor periphery, shifting hexose-to-Suc balance in favor of sugar signals for maturation and desiccation tolerance. Concurrent activities and sites of action for enzymes of Suc metabolism changed: Vacuolar invertase predominated during initial import of Suc into the symplastic continuum, corresponding to hexose concentrations in expanding tumors. Later, Suc synthase (SuSy) and cell wall invertase rose in the tumor periphery to modulate both Suc accumulation and descending turgor for import by metabolization. Sites of abscisic acid immunolocalization correlated with both central vacuolar invertase and peripheral cell wall invertase. Vascular roles were indicated by SuSy immunolocalization in xylem parenchyma for inorganic nutrient uptake and in phloem, where resolution allowed SuSy identification in sieve elements and companion cells, which has widespread implications for SuSy function in transport. Together, data indicate key roles for ethylene-dependent vascularization and cuticular disruption in the redirection of water flow and carbohydrate transport for successful tumor establishment.

Companions to α Orionis

NASA Astrophysics Data System (ADS)

Karovska, M.; Nisenson, P.; Noyes, R. W.; Stachnik, R.

Detection of two close optical companions to the red supergiant a Ori was accomplished using the PAPA detector for data recording, and speckle imaging for image reconstruction. Our analysis favors an interpretation in which the two optical sources are stellar companions to a Ori.The observed time dependent variations of the polarization of a Ori can be interpreted as being due to a systemic asymmetry created by one of the companions.

Defining the Architecture of the Core Machinery for the Assembly of Fe-S Clusters in Human Mitochondria.

PubMed

Gakh, Oleksandr; Ranatunga, Wasantha; Galeano, Belinda K; Smith, Douglas S; Thompson, James R; Isaya, Grazia

2017-01-01

Although Fe-S clusters may assemble spontaneously from elemental iron and sulfur in protein-free systems, the potential toxicity of free Fe 2+ , Fe 3+ , and S 2- ions in aerobic environments underscores the requirement for specialized proteins to oversee the safe assembly of Fe-S clusters in living cells. Prokaryotes first developed multiprotein systems for Fe-S cluster assembly, from which mitochondria later derived their own system and became the main Fe-S cluster suppliers for eukaryotic cells. Early studies in yeast and human mitochondria indicated that Fe-S cluster assembly in eukaryotes is centered around highly conserved Fe-S proteins (human ISCU) that serve as scaffolds upon which new Fe-S clusters are assembled from (i) elemental sulfur, provided by a pyridoxal phosphate-dependent cysteine desulfurase (human NFS1) and its stabilizing-binding partner (human ISD11), and (ii) elemental iron, provided by an iron-binding protein of the frataxin family (human FXN). Further studies revealed that all of these proteins could form stable complexes that could reach molecular masses of megadaltons. However, the protein-protein interaction surfaces, catalytic mechanisms, and overall architecture of these macromolecular machines remained undefined for quite some time. The delay was due to difficulties inherent in reconstituting these very large multiprotein complexes in vitro or isolating them from cells in sufficient quantities to enable biochemical and structural studies. Here, we describe approaches we developed to reconstitute the human Fe-S cluster assembly machinery in Escherichia coli and to define its remarkable architecture. © 2017 Elsevier Inc. All rights reserved.

Applications of Metal Additive Manufacturing in Veterinary Orthopedic Surgery

NASA Astrophysics Data System (ADS)

Harrysson, Ola L. A.; Marcellin-Little, Denis J.; Horn, Timothy J.

2015-03-01

Veterinary medicine has undergone a rapid increase in specialization over the last three decades. Veterinarians now routinely perform joint replacement, neurosurgery, limb-sparing surgery, interventional radiology, radiation therapy, and other complex medical procedures. Many procedures involve advanced imaging and surgical planning. Evidence-based medicine has also become part of the modus operandi of veterinary clinicians. Modeling and additive manufacturing can provide individualized or customized therapeutic solutions to support the management of companion animals with complex medical problems. The use of metal additive manufacturing is increasing in veterinary orthopedic surgery. This review describes and discusses current and potential applications of metal additive manufacturing in veterinary orthopedic surgery.

A conserved role for the ESCRT membrane budding complex in LINE retrotransposition

PubMed Central

Dong, Chun; Han, Jeffrey S.

2017-01-01

Long interspersed nuclear element-1s (LINE-1s, or L1s) are an active family of retrotransposable elements that continue to mutate mammalian genomes. Despite the large contribution of L1 to mammalian genome evolution, we do not know where active L1 particles (particles in the process of retrotransposition) are located in the cell, or how they move towards the nucleus, the site of L1 reverse transcription. Using a yeast model of LINE retrotransposition, we identified ESCRT (endosomal sorting complex required for transport) as a critical complex for LINE retrotransposition, and verified that this interaction is conserved for human L1. ESCRT interacts with L1 via a late domain motif, and this interaction facilitates L1 replication. Loss of the L1/ESCRT interaction does not impair RNP formation or enzymatic activity, but leads to loss of retrotransposition and reduced L1 endonuclease activity in the nucleus. This study highlights the importance of the ESCRT complex in the L1 life cycle and suggests an unusual mode for L1 RNP trafficking. PMID:28586350

Genetic addiction: selfish gene's strategy for symbiosis in the genome.

PubMed

Mochizuki, Atsushi; Yahara, Koji; Kobayashi, Ichizo; Iwasa, Yoh

2006-02-01

The evolution and maintenance of the phenomenon of postsegregational host killing or genetic addiction are paradoxical. In this phenomenon, a gene complex, once established in a genome, programs death of a host cell that has eliminated it. The intact form of the gene complex would survive in other members of the host population. It is controversial as to why these genetic elements are maintained, due to the lethal effects of host killing, or perhaps some other properties are beneficial to the host. We analyzed their population dynamics by analytical methods and computer simulations. Genetic addiction turned out to be advantageous to the gene complex in the presence of a competitor genetic element. The advantage is, however, limited in a population without spatial structure, such as that in a well-mixed liquid culture. In contrast, in a structured habitat, such as the surface of a solid medium, the addiction gene complex can increase in frequency, irrespective of its initial density. Our demonstration that genomes can evolve through acquisition of addiction genes has implications for the general question of how a genome can evolve as a community of potentially selfish genes.

Hubble Space Telescope Snapshot Survey for Resolved Companions of Galactic Cepheids

NASA Astrophysics Data System (ADS)

Evans, Nancy Remage; Bond, Howard E.; Schaefer, Gail H.; Mason, Brian D.; Tingle, Evan; Karovska, Margarita; Pillitteri, Ignazio

2016-05-01

We have conducted an imaging survey with the Hubble Space Telescope Wide Field Camera 3 (WFC3) of 70 Galactic Cepheids, typically within 1 kpc, with the aim of finding resolved physical companions. The WFC3 field typically covers the 0.1 pc area where companions are expected. In this paper, we identify 39 Cepheids having candidate companions, based on their positions in color-magnitude diagrams, and having separations ⩾ 5'' from the Cepheids. We use follow-up observations of 14 of these candidates with XMM-Newton, and of one of them with ROSAT, to separate X-ray-active young stars (probable physical companions) from field stars (chance alignments). Our preliminary estimate, based on the optical and X-ray observations, is that only 3% of the Cepheids in the sample have wide companions. Our survey easily detects resolved main-sequence companions as faint as spectral type K. Thus the fact that the two most probable companions (those of FF Aql and RV Sco) are earlier than type K is not simply a function of the detection limit. We find no physical companions having separations larger than 4000 au in the X-ray survey. Two Cepheids are exceptions in that they do have young companions at significantly larger separations (δ Cep and S Nor), but both belong to a cluster or a loose association, so our working model is that they are not gravitationally bound binary members, but rather cluster/association members. All of these properties provide constraints on both star formation and subsequent dynamical evolution. The low frequency of true physical companions at separations > 5'' is confirmed by examination of the subset of the nearest Cepheids and also the density of the fields. Based on observations with the NASA/ESA Hubble Space Telescope obtained at the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., under NASA contract NAS5-26555.

Hydrodynamic metamaterials: Microfabricated arrays to steer, refract, and focus streams of biomaterials

PubMed Central

Morton, Keith J.; Loutherback, Kevin; Inglis, David W.; Tsui, Ophelia K.; Sturm, James C.; Chou, Stephen Y.; Austin, Robert H.

2008-01-01

We show that it is possible to direct particles entrained in a fluid along trajectories much like rays of light in classical optics. A microstructured, asymmetric post array forms the core hydrodynamic element and is used as a building block to construct microfluidic metamaterials and to demonstrate refractive, focusing, and dispersive pathways for flowing beads and cells. The core element is based on the concept of deterministic lateral displacement where particles choose different paths through the asymmetric array based on their size: Particles larger than a critical size are displaced laterally at each row by a post and move along the asymmetric axis at an angle to the flow, while smaller particles move along streamline paths. We create compound elements with complex particle handling modes by tiling this core element using multiple transformation operations; we show that particle trajectories can be bent at an interface between two elements and that particles can be focused into hydrodynamic jets by using a single inlet port. Although particles propagate through these elements in a way that strongly resembles light rays propagating through optical elements, there are unique differences in the paths of our particles as compared with photons. The unusual aspects of these modular, microfluidic metamaterials form a rich design toolkit for mixing, separating, and analyzing cells and functional beads on-chip. PMID:18495920

Therapeutic regulatory T-cell adoptive transfer ameliorates established murine chronic GVHD in a CXCR5-dependent manner

PubMed Central

McDonald-Hyman, Cameron; Flynn, Ryan; Panoskaltsis-Mortari, Angela; Peterson, Nicholas; MacDonald, Kelli P. A.; Hill, Geoffrey R.; Luznik, Leo; Serody, Jonathan S.; Murphy, William J.; Maillard, Ivan; Munn, David H.; Turka, Laurence A.; Koreth, John; Cutler, Corey S.; Soiffer, Robert J.; Antin, Joseph H.; Ritz, Jerome

2016-01-01

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation. In cGVHD, alloreactive T cells and germinal center (GC) B cells often participate in GC reactions to produce pathogenic antibodies. Although regulatory T cells (Tregs) can inhibit GC reactions, Treg numbers are reduced in cGVHD, contributing to cGVHD pathogenesis. Here, we explored 2 means to increase Tregs in cGVHD: interleukin-2/monoclonal antibody (IL-2/mAb) complexes and donor Treg infusions. IL-2/mAb complexes given over 1 month were efficacious in expanding Tregs and treating established cGVHD in a multi-organ-system disease mouse model characterized by GC reactions, antibody deposition, and lung dysfunction. In an acute GVHD (aGVHD) model, IL-2/mAb complexes given for only 4 days resulted in rapid mortality, indicating IL-2/mAb complexes can drive conventional T-cell (Tcon)-mediated injury. In contrast, Treg infusions, which uniformly suppress aGVHD, increased Treg frequency and were effective in preventing the onset of, and treating, established cGVHD. Efficacy was dependent upon CXCR5-sufficient Tregs homing to, and inhibiting, GC reactions. These studies indicate that the infusion of Tregs, especially ones enriched for GC homing, may be desirable for cGVHD therapy. Although IL-2/mAb complexes can be efficacious in cGVHD, a cautious approach needs to be taken in settings in which aGVHD elements, and associated Tcon, are present. PMID:27385791

"Let him speak:" a descriptive qualitative study of the roles and behaviors of family companions in primary care visits among older adults with cognitive impairment.

PubMed

Vick, Judith B; Amjad, Halima; Smith, Katherine C; Boyd, Cynthia M; Gitlin, Laura N; Roth, David L; Roter, Debra L; Wolff, Jennifer L

2018-01-01

Cognitive impairment poses communication challenges in primary care. Although family "companions" commonly attend primary care visits of older adults with cognitive impairment, little is known about how their involvement affects communication. Therefore, we sought to understand how companion involvement affects the quality of primary care visit communication for older adults with cognitive impairment. Cross-sectional, descriptive qualitative study participants were as follows: (1) English-speaking adults age 65 or older with mild, moderate, or severe cognitive impairment; (2) family members or other unpaid companions who accompany older adults to primary care visits; and (3) primary care clinicians. Twenty semi-structured and in-depth qualitative interviews of older adults and their companions (N = 20 dyads) and two focus groups (N = 10 primary care clinicians) were conducted. Interviews and focus groups were transcribed and analyzed thematically. Family companions commonly facilitate communication by advocating for patients, ensuring the accuracy of information exchange and understanding, and preserving rapport. Significant communication challenges were also identified, including patient and companion role ambiguity, competing visit agendas, and primary care clinician confusion regarding the most accurate source of information. Patients, companions, and clinicians each identified strategies to improve communication, chief among them being to identify, differentiate, and respect both patient and companion priorities and perspectives. Family companions actively participate in primary care visits of older adults with cognitive impairment in ways that promote and inhibit effective communication. Findings suggest the need for strategies that more effectively and purposefully involve family in the care of primary care patients with cognitive impairment. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

A High Resolution Phase Shifting Interferometer.

NASA Astrophysics Data System (ADS)

Bayda, Michael; Bartscher, Christoph; Wilkinson, Allen

1997-03-01

Configuration, operation, and performance details of a high resolution phase shifting Twyman-Green interferometer are presented. The instrument was used for density relaxation experiments of very compressible liquid-vapor critical fluids.(A companion talk in the Nonequilibrium Phenomena session under Complex Fluids presents density equilibration work.) A sample assembly contained the cell, beam splitter, phase shifter, and mirrors inside a 6 cm diameter by 6 cm long aluminum cylinder. This sample assembly was contained inside a thermostat stable to 50 μK RMS deviation. A thin phase retarding Liquid Crystal Cell (LCC) was placed in the reference arm of the interferometer. The LCC provided four cumulative 90 degree phase shifts to produce four images used in computing each phase map. The Carré technique was used to calculate a phase value for each pixel from the four intensities of each pixel. Four images for one phase map could be acquired in less than two seconds. The spatial resolution was 25 μm. The phase resolution of the interferometer in a six second period was better than λ/400. The phase stability of the interferometer during 25 hours was better than λ/70. Factors affecting timing, resolution, and other phase shifting devices will be discussed. WWW Presentation

Outlier analysis of functional genomic profiles enriches for oncology targets and enables precision medicine.

PubMed

Zhu, Zhou; Ihle, Nathan T; Rejto, Paul A; Zarrinkar, Patrick P

2016-06-13

Genome-scale functional genomic screens across large cell line panels provide a rich resource for discovering tumor vulnerabilities that can lead to the next generation of targeted therapies. Their data analysis typically has focused on identifying genes whose knockdown enhances response in various pre-defined genetic contexts, which are limited by biological complexities as well as the incompleteness of our knowledge. We thus introduce a complementary data mining strategy to identify genes with exceptional sensitivity in subsets, or outlier groups, of cell lines, allowing an unbiased analysis without any a priori assumption about the underlying biology of dependency. Genes with outlier features are strongly and specifically enriched with those known to be associated with cancer and relevant biological processes, despite no a priori knowledge being used to drive the analysis. Identification of exceptional responders (outliers) may not lead only to new candidates for therapeutic intervention, but also tumor indications and response biomarkers for companion precision medicine strategies. Several tumor suppressors have an outlier sensitivity pattern, supporting and generalizing the notion that tumor suppressors can play context-dependent oncogenic roles. The novel application of outlier analysis described here demonstrates a systematic and data-driven analytical strategy to decipher large-scale functional genomic data for oncology target and precision medicine discoveries.

The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.

PubMed Central

Poon, R Y; Yamashita, K; Adamczewski, J P; Hunt, T; Shuttleworth, J

1993-01-01

Activation of the cyclin-dependent protein kinases p34cdc2 and p33cdk2 requires binding with a cyclin partner and phosphorylation on the first threonine residue in the sequence THEVVTLWYRAPE. We present evidence that this threonine residue, number 160 in p33cdk2, can be specifically phosphorylated by a cdc2-related protein kinase from Xenopus oocytes called p40MO15. Binding to cyclin A and phosphorylation of this threonine are both required to activate fully the histone H1 kinase activity of p33cdk2. In cell extracts, a portion of p40MO15 is found in a high molecular weight complex that is considerably more active than a lower molecular weight form. Wild-type MO15 protein expressed in bacteria does not possess kinase activity, but acquires p33cdk2-T160 kinase activity after incubation with cell extract and ATP. We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and association with a companion subunit. Images PMID:8393783

The cdc2-related protein p40MO15 is the catalytic subunit of a protein kinase that can activate p33cdk2 and p34cdc2.

PubMed

Poon, R Y; Yamashita, K; Adamczewski, J P; Hunt, T; Shuttleworth, J

1993-08-01

Activation of the cyclin-dependent protein kinases p34cdc2 and p33cdk2 requires binding with a cyclin partner and phosphorylation on the first threonine residue in the sequence THEVVTLWYRAPE. We present evidence that this threonine residue, number 160 in p33cdk2, can be specifically phosphorylated by a cdc2-related protein kinase from Xenopus oocytes called p40MO15. Binding to cyclin A and phosphorylation of this threonine are both required to activate fully the histone H1 kinase activity of p33cdk2. In cell extracts, a portion of p40MO15 is found in a high molecular weight complex that is considerably more active than a lower molecular weight form. Wild-type MO15 protein expressed in bacteria does not possess kinase activity, but acquires p33cdk2-T160 kinase activity after incubation with cell extract and ATP. We conclude that p40MO15 corresponds to CAK (cdc2/cdk2 activating kinase) and speculate that, like p33cdk2 and p34cdc2, p40MO15 requires activation by phosphorylation and association with a companion subunit.

The meaning of PIWI proteins in cancer development.

PubMed

Litwin, Monika; Szczepańska-Buda, Anna; Piotrowska, Aleksandra; Dzięgiel, Piotr; Witkiewicz, Wojciech

2017-05-01

Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed.

The meaning of PIWI proteins in cancer development

PubMed Central

Litwin, Monika; Szczepańska-Buda, Anna; Piotrowska, Aleksandra; Dzięgiel, Piotr; Witkiewicz, Wojciech

2017-01-01

Cancer is a histologically and genetically heterogeneous population of tumor cells that exhibits distinct molecular profiles determined by epigenetic alterations. P-element-induced wimpy testis (PIWI) proteins in complex with PIWI-interacting RNA (piRNA) have been previously demonstrated to be involved in epigenetic regulation in germline cells. Recently, reactivation of PIWI expression, primarily PIWI-like protein 1 and 2, through aberrant DNA methylation resulting in genomic silencing has been identified in various types of tumors. It has been suggested that the PIWI-piRNA complex contributes to cancer development and progression by promoting a stem-like state of cancer cells, or cancer stem cells (CSCs). It has been identified that CSCs represent the cells that have undergone epithelial-mesenchymal transition (EMT) and acquired metastatic capacities. However, the molecular association between the EMT process and the stem-cell state remains unclear. Further extensive characterization of CSCs in individual types of tumors is required to identify specific markers for the heterogeneous population of CSCs and therefore selectively target CSCs. Previous studies indicate a reciprocal regulation between PIWI proteins and a complex signaling network linking markers characterized for CSCs and transcription factors involved in EMT. In the present review, studies of PIWI function are summarized, and the potential involvement of PIWI proteins in cancer development and progression is discussed. PMID:28529570

Impact of Availability of Companion Diagnostics on the Clinical Development of Anticancer Drugs.

PubMed

Tibau, Ariadna; Díez-González, Laura; Navarro, Beatriz; Galán-Moya, Eva M; Templeton, Arnoud J; Seruga, Bostjan; Pandiella, Atanasio; Amir, Eitan; Ocana, Alberto

2017-06-01

Companion diagnostics permit the selection of patients likely to respond to targeted anticancer drugs; however, it is unclear if the drug development process differs between drugs developed with or without companion diagnostics. Identification of differences in study design could help future clinical development. Anticancer drugs approved for use in solid tumors between 28 September 2000 and 4 January 2014 were identified using a search of the US FDA website. Phase III trials supporting registration were extracted from the drug label. Each published study was reviewed to obtain information about the phase I and II trials used for the development of the respective drug. We identified 35 drugs and 59 phase III randomized trials supporting regulatory approval. Fifty-three phase I trials and 47 phase II trials were cited in the studies and were used to support the design of these phase III trials. The approval of drugs using a companion diagnostic has increased over time (p for trend 0.01). Expansion cohorts were more frequently observed with drugs developed with a companion diagnostic (62 vs. 20%; p = 0.005). No differences between drugs developed with or without a companion diagnostic were observed for the design of phase I and II studies. The approval of drugs developed with a companion diagnostic has increased over time. The availability of a companion diagnostic was associated with more frequent use of phase I expansion cohorts comprising patients selected by the companion diagnostic.

A fast method for finding bound systems in numerical simulations: Results from the formation of asteroid binaries

NASA Astrophysics Data System (ADS)

Leinhardt, Zoë M.; Richardson, Derek C.

2005-08-01

We present a new code ( companion) that identifies bound systems of particles in O(NlogN) time. Simple binaries consisting of pairs of mutually bound particles and complex hierarchies consisting of collections of mutually bound particles are identifiable with this code. In comparison, brute force binary search methods scale as O(N) while full hierarchy searches can be as expensive as O(N), making analysis highly inefficient for multiple data sets with N≳10. A simple test case is provided to illustrate the method. Timing tests demonstrating O(NlogN) scaling with the new code on real data are presented. We apply our method to data from asteroid satellite simulations [Durda et al., 2004. Icarus 167, 382-396; Erratum: Icarus 170, 242; reprinted article: Icarus 170, 243-257] and note interesting multi-particle configurations. The code is available at http://www.astro.umd.edu/zoe/companion/ and is distributed under the terms and conditions of the GNU Public License.

Studying the inner regions of young stars and their disks with aperture masking interferometry

NASA Astrophysics Data System (ADS)

Greenbaum, Alexandra; Sivaramakrishnan, Anand; GPI Instrument Team; NIRISS Instrument Team

2017-01-01

High resolution aperture masking interferometry complements coronagraphic imagers to provide a unique perspective on star and planet formation at more moderate contrast. By targeting young stars, especially those with disks, we aim to understand complex protoplanetary environments. Ground-based non-redundant masking (NRM) paired with spectrographs and polarimeters probes both thermally emitting young companions, possibly embedded in the disk or gap and scattered light in protoplanetary disks. And soon the community will have access to the most stable NRM conditions yet, with the Near Infrared Imager and Slitless Spectrograph (NIRISS) Aperture Masking Interferometry (AMI) mode on the James Webb Space Telescope. I will present my thesis work commissioning the Gemini Planet Imager’s NRM, highlighting results through both its spectroscopy and polarimetry modes, which set the stage for future space-based imaging. I will also give an overview of NIRISS-AMI capabilities and performance predictions for imaging young low-mass companions and disks, and how it will complement other instruments on JWST.

A cut-cell finite volume – finite element coupling approach for fluid–structure interaction in compressible flow

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pasquariello, Vito, E-mail: vito.pasquariello@tum.de; Hammerl, Georg; Örley, Felix

2016-02-15

We present a loosely coupled approach for the solution of fluid–structure interaction problems between a compressible flow and a deformable structure. The method is based on staggered Dirichlet–Neumann partitioning. The interface motion in the Eulerian frame is accounted for by a conservative cut-cell Immersed Boundary method. The present approach enables sub-cell resolution by considering individual cut-elements within a single fluid cell, which guarantees an accurate representation of the time-varying solid interface. The cut-cell procedure inevitably leads to non-matching interfaces, demanding for a special treatment. A Mortar method is chosen in order to obtain a conservative and consistent load transfer. Wemore » validate our method by investigating two-dimensional test cases comprising a shock-loaded rigid cylinder and a deformable panel. Moreover, the aeroelastic instability of a thin plate structure is studied with a focus on the prediction of flutter onset. Finally, we propose a three-dimensional fluid–structure interaction test case of a flexible inflated thin shell interacting with a shock wave involving large and complex structural deformations.« less

Quantifying the deformation of the red blood cell skeleton in shear flow

NASA Astrophysics Data System (ADS)

Peng, Zhangli; Zhu, Qiang

2012-02-01

To quantitatively predict the response of red blood cell (RBC) membrane in shear flow, we carried out multiphysics simulations by coupling a three-level multiscale approach of RBC membranes with a Boundary Element Method (BEM) for surrounding flows. Our multiscale approach includes a model of spectrins with the domain unfolding feature, a molecular-based model of the junctional complex with detailed protein connectivity and a whole cell Finite Element Method (FEM) model with the bilayer-skeleton friction derived from measured transmembrane protein diffusivity based on the Einstein-Stokes relation. Applying this approach, we investigated the bilayer-skeleton slip and skeleton deformation of healthy RBCs and RBCs with hereditary spherocytosis anemia during tank-treading motion. Compared with healthy cells, cells with hereditary spherocytosis anemia sustain much larger skeleton-bilayer slip and area deformation of the skeleton due to deficiency of transmembrane proteins. This leads to extremely low skeleton density and large bilayer-skeleton interaction force, both of which may cause bilayer loss. This finding suggests a possible mechanism of the development of hereditary spherocytosis anemia.

Computer modeling of batteries from nonlinear circuit elements

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waaben, S.; Dyer, C.K.; Federico, J.

1985-06-01

Circuit analogs for a single battery cell have previously been composed of resistors, capacitors, and inductors. This work introduces a nonlinear circuit model for cell behavior. The circuit is configured around the PIN junction diode, whose charge-storage behavior has features similar to those of electrochemical cells. A user-friendly integrated circuit simulation computer program has reproduced a variety of complex cell responses including electrica isolation effects causing capacity loss, as well as potentiodynamic peaks and discharge phenomena hitherto thought to be thermodynamic in origin. However, in this work, they are shown to be simply due to spatial distribution of stored chargemore » within a practical electrode.« less

Bacterial Cell Mechanics.

PubMed

Auer, George K; Weibel, Douglas B

2017-07-25

Cellular mechanical properties play an integral role in bacterial survival and adaptation. Historically, the bacterial cell wall and, in particular, the layer of polymeric material called the peptidoglycan were the elements to which cell mechanics could be primarily attributed. Disrupting the biochemical machinery that assembles the peptidoglycan (e.g., using the β-lactam family of antibiotics) alters the structure of this material, leads to mechanical defects, and results in cell lysis. Decades after the discovery of peptidoglycan-synthesizing enzymes, the mechanisms that underlie their positioning and regulation are still not entirely understood. In addition, recent evidence suggests a diverse group of other biochemical elements influence bacterial cell mechanics, may be regulated by new cellular mechanisms, and may be triggered in different environmental contexts to enable cell adaptation and survival. This review summarizes the contributions that different biomolecular components of the cell wall (e.g., lipopolysaccharides, wall and lipoteichoic acids, lipid bilayers, peptidoglycan, and proteins) make to Gram-negative and Gram-positive bacterial cell mechanics. We discuss the contribution of individual proteins and macromolecular complexes in cell mechanics and the tools that make it possible to quantitatively decipher the biochemical machinery that contributes to bacterial cell mechanics. Advances in this area may provide insight into new biology and influence the development of antibacterial chemotherapies.

Agronomical, biochemical and histological response of resistant and susceptible wheat and barley under BYDV stress

PubMed Central

Choudhury, Shormin; Hu, Hongliang; Larkin, Philip; Meinke, Holger; Shabala, Sergey; Ahmed, Ibrahim

2018-01-01

Barley yellow dwarf virus-PAV (BYDV-PAV) is one of the major viruses causing a widespread and serious viral disease affecting cereal crops. To gain a better understanding of plant defence mechanisms of BYDV resistance genes (Bdv2 and RYd2) against BYDV-PAV infection, the differences in agronomical, biochemical and histological changes between susceptible and resistant wheat and barley cultivars were investigated. We found that root growth and total dry matter of susceptible cultivars showed greater reduction than that of resistant ones after infection. BYDV infected leaves in susceptible wheat and barley cultivars showed a significant reduction in photosynthetic pigments, an increase in the concentration of reducing sugar. The protein levels were also low in infected leaves. There was a significant increase in total phenol contents in resistant cultivars, which might reflect a protective mechanism of plants against virus infection. In phloem tissue, sieve elements (SE) and companion cells (CC) were severely damaged in susceptible cultivars after infection. It is suggested that restriction of viral movement in the phloem tissue and increased production of phenolic compounds may play a role in the resistance and defensive mechanisms of both Bdv2 and RYd2 against virus infection. PMID:29868264

Synthesis, spectroscopic characterization, electrochemical behavior and computational analysis of mixed diamine ligand gold(III) complexes: antiproliferative and in vitro cytotoxic evaluations against human cancer cell lines.

PubMed

Al-Jaroudi, Said S; Monim-ul-Mehboob, M; Altaf, Muhammad; Al-Saadi, Abdulaziz A; Wazeer, Mohammed I M; Altuwaijri, Saleh; Isab, Anvarhusein A

2014-12-01

The gold(III) complexes of the type [(DACH)Au(en)]Cl3, 1,2-Diaminocyclohexane ethylenediamine gold(III) chloride [where 1,2-DACH = cis-, trans-1,2- and S,S-1,2diaminocyclohexane and en = ethylenediamine] have been synthesized and characterized using various analytical and spectroscopic techniques including elemental analysis, UV-Vis and FTIR spectra; and solution as well as solid-state NMR measurements. The solid-state (13)C NMR shows that 1,2-diaminocyclohexane (1,2-DACH) and ethylenediamine (en) are strongly bound to the gold(III) center via N donor atoms. The stability of the mixed diamine ligand gold(III) was determined by (1)H and (13)C NMR spectra. Their electrochemical behavior was studied by cyclic voltammetry. The structural details and relative stabilities of the four possible isomers of the complexes were also reported at the B3LYP/LANL2DZ level of theory. The coordination sphere of these complexes around gold(III) center adopts distorted square planar geometry. The computational study also demonstrates that trans- conformations is slightly more stable than the cis-conformations. The antiproliferative effects and cytotoxic properties of the mixed diamine ligand gold(III) complexes were evaluated in vitro on human gastric SGC7901 and prostate PC3 cancer cells using MTT assay. The antiproliferative study of the gold(III) complexes on PC3 and SGC7901 cells indicate that complex 1 is the most effective antiproliferative agent among mixed ligand based gold(III) complexes 1-3. The IC50 data reveal that the in vitro cytotoxicity of complexes 1 and 3 against SGC7901 cancer cells are fairly better than that of cisplatin.

Aldosterone alters the chromatin structure of the murine endothelin-1 gene.

PubMed

Welch, Amanda K; Jeanette Lynch, I; Gumz, Michelle L; Cain, Brian D; Wingo, Charles S

2016-08-15

Aldosterone increases sodium reabsorption in the renal collecting duct and systemic blood pressure. Paradoxically, aldosterone also induces transcription of the endothelin-1 (Edn1) gene to increase protein (ET-1) levels, which inhibits sodium reabsorption. Here we investigated changes in the chromatin structure of the Edn1 gene of collecting duct cell lines in response to aldosterone treatment. The Edn1 gene has a CpG island that encompasses the transcription start site and four sites in the 5' regulatory region previously linked to transcriptional regulation. The chromatin structure of the Edn1 gene was investigated using a quantitative PCR-based DNaseI hypersensitivity assay in murine hepatocyte (AML12), renal cortical collecting duct (mpkCCDC14), outer medullary collecting duct1 (OMCD1), and inner medullary collecting duct-3 (IMCD-3) cell lines. The CpG island was uniformly accessible. One calcium-responsive NFAT element remained at low chromatin accessibility in all cell lines under all conditions tested. However, the second calcium responsive NFAT element located at -1563bp upstream became markedly more accessible in IMCD-3 cells exposed to aldosterone. Importantly, one established aldosterone hormone response element HRE at -671bp relative to the transcription start site was highly accessible, and another HRE (-551bp) became more accessible in aldosterone-treated IMCD-3 and OMCD1 cells. The evidence supports a model in which aldosterone activation of the mineralocorticoid receptor (MR) results in the MR-hormone complex binding at HRE at -671bp to open chromatin structure around other regulatory elements in the Edn1 gene. Published by Elsevier Inc.

The Role of microRNA miR-101 in Prostate Cancer Progression

DTIC Science & Technology

2012-09-01

genome -wide mapping of PcG binding in human fibroblasts, human ES cells, mouse ES cells, and Drosophila 37-41 . All of the studies demonstrated that...development. Mamm Genome 2002; 13(9): 493-503. 15. Simon J, Chiang A, Bender W, Shimell MJ, O’Connor M. Elements of the Drosophila bithorax complex... sequencing analysis of the miR-203 genomic region revealed cancer-specific DNA methylation in a region proximal to miR-203 in prostate cancer tissues

Studies of the Mu-Opioid Receptor/G-protein Complex Affinity Co-Purified and Membrane Preparations from 7315c Cells

DTIC Science & Technology

1989-06-09

centrifugational sedimentation rates of the GTPys- activated and inactivated purified Gs (Birnbaumer et al., 1985). Recently, different antibodies raised against...and Membrane Preparations from 7315c Cells 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...were shown to be fused with the 1 membranes from turkey erythrocytes that have ~-adrenergic receptors but inactive adenylyl cyclase activity due to

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics

PubMed Central

AlAjmi, Mohamed F.; Hussain, Afzal; Khan, Azmat Ali; Shaikh, Perwez Alam; Khan, Rais Ahmad

2018-01-01

Herein, we have synthesized and characterized a new benzimidazole-derived “BnI” ligand and its copper(II) complex, [Cu(BnI)2], 1, and zinc(II) complex, [Zn(BnI)2], 2, using elemental analysis and various spectroscopic techniques. Interaction of complexes 1 and 2 with the biomolecules viz. HSA (human serum albumin) and DNA were studied using absorption titration, fluorescence techniques, and in silico molecular docking studies. The results exhibited the significant binding propensity of both complexes 1 and 2, but complex 1 showed more avid binding to HSA and DNA. Also, the nuclease activity of 1 and 2 was analyzed for pBR322 DNA, and the results obtained confirmed the potential of the complexes to cleave DNA. Moreover, the mechanistic pathway was studied in the presence of various radical scavengers, which revealed that ROS (reactive oxygen species) are responsible for the nuclease activity in complex 1, whereas in complex 2, the possibility of hydrolytic cleavage also exists. Furthermore, the cytotoxicity of the ligand and complexes 1 and 2 were studied on a panel of five different human cancer cells, namely: HepG2, SK-MEL-1, HT018, HeLa, and MDA-MB 231, and compared with the standard drug, cisplatin. The results are quite promising against MDA-MB 231 (breast cancer cell line of 1), with an IC50 value that is nearly the same as the standard drug. Apoptosis was induced by complex 1 on MDA-MB 231 cells predominantly as studied by flow cytometry (FACS). The adhesion and migration of cancer cells were also examined upon treatment of complexes 1 and 2. Furthermore, the in vivo chronic toxicity profile of complexes 1 and 2 was also studied on all of the major organs of the mice, and found them to be less toxic. Thus, the results warrant further investigations of complex 1. PMID:29772746

Design, Synthesis, and Biological Evaluation of Benzimidazole-Derived Biocompatible Copper(II) and Zinc(II) Complexes as Anticancer Chemotherapeutics.

PubMed

AlAjmi, Mohamed F; Hussain, Afzal; Rehman, Md Tabish; Khan, Azmat Ali; Shaikh, Perwez Alam; Khan, Rais Ahmad

2018-05-16

Herein, we have synthesized and characterized a new benzimidazole-derived "BnI" ligand and its copper(II) complex, [Cu(BnI)₂], 1 , and zinc(II) complex, [Zn(BnI)₂], 2 , using elemental analysis and various spectroscopic techniques. Interaction of complexes 1 and 2 with the biomolecules viz. HSA (human serum albumin) and DNA were studied using absorption titration, fluorescence techniques, and in silico molecular docking studies. The results exhibited the significant binding propensity of both complexes 1 and 2 , but complex 1 showed more avid binding to HSA and DNA. Also, the nuclease activity of 1 and 2 was analyzed for pBR322 DNA, and the results obtained confirmed the potential of the complexes to cleave DNA. Moreover, the mechanistic pathway was studied in the presence of various radical scavengers, which revealed that ROS (reactive oxygen species) are responsible for the nuclease activity in complex 1 , whereas in complex 2 , the possibility of hydrolytic cleavage also exists. Furthermore, the cytotoxicity of the ligand and complexes 1 and 2 were studied on a panel of five different human cancer cells, namely: HepG2, SK-MEL-1, HT018, HeLa, and MDA-MB 231, and compared with the standard drug, cisplatin. The results are quite promising against MDA-MB 231 (breast cancer cell line of 1 ), with an IC 50 value that is nearly the same as the standard drug. Apoptosis was induced by complex 1 on MDA-MB 231 cells predominantly as studied by flow cytometry (FACS). The adhesion and migration of cancer cells were also examined upon treatment of complexes 1 and 2 . Furthermore, the in vivo chronic toxicity profile of complexes 1 and 2 was also studied on all of the major organs of the mice, and found them to be less toxic. Thus, the results warrant further investigations of complex 1 .

Social Support Versus Social Evaluation: Unique Effects on Vascular and Myocardial Response Patterns

PubMed Central

Christian, Lisa M.; Stoney, Catherine M.

2010-01-01

Objectives This study examined the effects of companion presence and evaluation on cardiovascular reactivity to an acute stressor. Methods Eighty-two women completed a speech task in one of four conditions: with an evaluative companion present, with a nonevaluative companion present, alone while being evaluated by a companion with a video camera, or alone while the companion waited outside. Results A significant interaction between companion condition and evaluative condition on systolic blood pressure was found; women who were evaluated while alone demonstrated significantly greater reactivity than did women who were in the nonevaluative alone condition. Furthermore, both potential for evaluation and the presence of a companion had important influences on hemodynamic parameters underlying the blood pressure response. Specifically, those in evaluative conditions showed greater myocardial responding than those in nonevaluative conditions and those in alone conditions showed greater vascular responding than did those with companions present. Taken together, those in the evaluative alone condition demonstrated systolic blood pressure responses reflecting both myocardial and vascular contributions. Conclusions Social support and social evaluation have unique effects on vascular and myocardial responding. The implications for future research include focus on the stress-buffering model of social support and the value of including impedance cardiography measures in investigations of cardiovascular functioning. PMID:17079702

[Regulation of immune responses by exosomes derived from antigen presenting cells].

PubMed

Maravillas-Montero, José Luis; Martínez-Cortés, Ismael

2017-01-01

Cells release several biomolecules to the extracellular environment using them as a communication alternative with neighbor cells. Besides these molecules, cells also release more complex elements, like vesicles; structures composed of a lipidic bilayer with transmembrane proteins that protect a hydrophilic content. Exosomes are a small subtype of vesicles (30-150 nm), produced by many cell types, such as tumor cells, neurons, epithelial cells and immune cells. Included in this last group, antigen presenting cells produce exosomes that contain different types of molecules depending on their activation and/or maturation state. In recent years there has been an exponential interest in exosomes due to the recent evidences that show the immunomodulatory properties of these vesicles and therefore, their great potential in diagnostic approaches and development of therapies for different inflammation-associated pathologies.

I-Wire Heart-on-a-Chip II: Biomechanical analysis of contractile, three-dimensional cardiomyocyte tissue constructs.

PubMed

Schroer, Alison K; Shotwell, Matthew S; Sidorov, Veniamin Y; Wikswo, John P; Merryman, W David

2017-01-15

This companion study presents the biomechanical analysis of the "I-Wire" platform using a modified Hill model of muscle mechanics that allows for further characterization of construct function and response to perturbation. The I-Wire engineered cardiac tissue construct (ECTC) is a novel experimental platform to investigate cardiac cell mechanics during auxotonic contraction. Whereas passive biomaterials often exhibit nonlinear and dissipative behavior, active tissue equivalents, such as ECTCs, also expend metabolic energy to perform mechanical work that presents additional challenges in quantifying their properties. The I-Wire model uses the passive mechanical response to increasing applied tension to measure the inherent stress and resistance to stretch of the construct before, during, and after treatments. Both blebbistatin and isoproterenol reduced prestress and construct stiffness; however, blebbistatin treatment abolished subsequent force-generating potential while isoproterenol enhanced this property. We demonstrate that the described model can replicate the response of these constructs to intrinsic changes in force-generating potential in response to both increasing frequency of stimulation and decreasing starting length. This analysis provides a useful mathematical model of the I-Wire platform, increases the number of parameters that can be derived from the device, and serves as a demonstration of quantitative characterization of nonlinear, active biomaterials. We anticipate that this quantitative analysis of I-Wire constructs will prove useful for qualifying patient-specific cardiomyocytes and fibroblasts prior to their utilization for cardiac regenerative medicine. Passive biomaterials may have non-linear elasticity and losses, but engineered muscle tissue also exhibits time- and force-dependent contractions. Historically, mathematical muscle models include series-elastic, parallel-elastic, contractile, and viscous elements. While hearts-on-a-chip can demonstrate in vitro the contractile properties of engineered cardiac constructs and their response to drugs, most of these use cellular monolayers that cannot be readily probed with controlled forces. The I-Wire platform described in the preceding paper by Sidorov et al. addresses these limitations with three-dimensional tissue constructs to which controlled forces can be applied. In this companion paper, we show how to characterize I-Wire constructs using a non-linear, active Hill model, which should be useful for qualifying cells prior to their use in cardiac regenerative medicine. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

A functionally conserved Polycomb response element from mouse HoxD complex responds to heterochromatin factors

NASA Astrophysics Data System (ADS)

Vasanthi, Dasari; Nagabhushan, A.; Matharu, Navneet Kaur; Mishra, Rakesh K.

2013-10-01

Anterior-posterior body axis in all bilaterians is determined by the Hox gene clusters that are activated in a spatio-temporal order. This expression pattern of Hox genes is established and maintained by regulatory mechanisms that involve higher order chromatin structure and Polycomb group (PcG) and trithorax group (trxG) proteins. We identified earlier a Polycomb response element (PRE) in the mouse HoxD complex that is functionally conserved in flies. We analyzed the molecular and genetic interactions of mouse PRE using Drosophila melanogaster and vertebrate cell culture as the model systems. We demonstrate that the repressive activity of this PRE depends on PcG/trxG genes as well as the heterochromatin components. Our findings indicate that a wide range of factors interact with the HoxD PRE that can contribute to establishing the expression pattern of homeotic genes in the complex early during development and maintain that pattern at subsequent stages.

Synthesis, interaction with DNA and bovine serum albumin of the transition metal complexes of demethylcantharate and 2-aminobenzothiazole

NASA Astrophysics Data System (ADS)

Zhang, Fan; Lin, Qiu-Yue; Li, Shi-Kun; Zhao, Yu-Ling; Wang, Peng-Peng; Chen, Miao-Miao

2012-12-01

Four new transition metal complexes (Habtz)2[M(DCA)2]·6H2O (M = Co(II) (1), Ni(II) (2), Cu(II) (3), Zn(II) (4); DCA = demethylcantharate, 7-oxabicyclo [2.2.1]heptane-2,3-dicarboxylate, C8H8O5; Habtz = 2-aminobenzothiazole acid, C7H7N2S) were synthesized and characterized by elemental analysis, molar conductance, infrared spectra and thermogravimetric analysis. The coordination number of complex was six. The X-ray diffraction analysis indicated that complex 3 crystallized in the triclinic crystal system with P1¯ space group. The DNA-binding properties of the complexes were investigated by electronic absorption spectra, fluorescence spectra, viscosity measurements. Title complexes could bind to DNA via partial intercalative mode. The Kb of the complexes were 5.33 × 104 (1), 7.04 × 104 (2), 9.91 × 104 (3) and 5.03 × 104 L mol-1 (4). The results of agarose gel electrophoresis showed that Cu(II) complex could cleave pBR322 plasmid DNA via radical-based mechanism. The complexes could quench the intrinsic fluorescence of bovine serum albumin (BSA) through a static quenching with the binding constants Ka of 1.11 × 104 (1), 1.24 × 106 (2), 8.42 × 105 (3) and 1.75 × 104 L mol-1 (4). The complexes had intense antiproliferative activities against human hepatoma cell lines (SMMC7721) and human gastric cancer cells (MGC80-3) lines in vitro. Cu(II) complex had the strongest activity against human gastric cancer cells.

In vitro antitumor activity, metal uptake and reactivity with ascorbic acid and BSA of some gold(III) complexes with N,N'-ethylenediamine bidentate ester ligands.

PubMed

Pantelić, Nebojša; Zmejkovski, Bojana B; Kolundžija, Branka; Crnogorac, Marija Đorđić; Vujić, Jelena M; Dojčinović, Biljana; Trifunović, Srećko R; Stanojković, Tatjana P; Sabo, Tibor J; Kaluđerović, Goran N

2017-07-01

Four novel gold(III) complexes of general formulae [AuCl 2 {(S,S)-R 2 eddl}]PF 6 (R 2 eddl=O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R=n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24h, and for the reaction with ascorbic acid in which was reduced immediately. Additionally, 3 interacts with bovine serum albumin (BSA) as proven by UV/Vis spectroscopy. In vitro antitumor activity was determined against human cervix adenocarcinoma (HeLa), human myelogenous leukemia (K562), and human melanoma (Fem-x) cancer cell lines, as well as against non-cancerous human embryonic lung fibroblast cells MRC-5. The highest activity was observed against K562 cells (IC 50 : 5.04-6.51μM). Selectivity indices showed that these complexes are less toxic than cisplatin. 3 had a similar viability kinetics on HeLa cells as cisplatin. Drug accumulation studies in HeLa cells showed that the total gold uptake increased much faster than that of cisplatin pointing out that 3 more efficiently enters the cells than cisplatin. Furthermore, morphological and cell cycle analysis reveal that gold(III) complexes induced apoptosis in time- and dose-dependent manner. Copyright © 2017 Elsevier Inc. All rights reserved.

Identification and characterization of a silencer regulatory element in the 3'-flanking region of the murine CD46 gene.

PubMed Central

Nomura, M; Tsujimura, A; Begum, N A; Matsumoto, M; Wabiko, H; Toyoshima, K; Seya, T

2000-01-01

The murine membrane cofactor protein (CD46) gene is expressed exclusively in testis, in contrast to human CD46, which is expressed ubiquitously. To elucidate the mechanism of differential CD46 gene expression among species, we cloned entire murine CD46 genomic DNA and possible regulatory regions were placed in the flanking region of the luciferase reporter gene. The reporter gene assay revealed a silencing activity not in the promoter, but in the 3'-flanking region of the gene and the silencer-like element was identified within a 0.2-kb region between 0.6 and 0.8 kb downstream of the stop codon. This silencer-like element was highly similar to that of the pig MHC class-I gene. The introduction of a mutation into this putative silencer element of murine CD46 resulted in an abrogation of the silencing effect. Electrophoretic mobility-shift assay indicated the presence of the binding molecule(s) for this silencer sequence in murine cell lines and tissues. A size difference of the protein-silencer-element complex was observed depending upon the solubilizers used for preparation of the nuclear extracts. A mutated silencer sequence failed to interact with the binding molecules. The level of the binding factor was lower in the testicular germ cells compared with other organs. Thus the silencer element and its binding factor may play a role in transcriptional regulation of murine CD46 gene expression. These results imply that the effects of the CD46 silencer element encompass the innate immune and reproductive systems, and in mice may determine the testicular germ-cell-dominant expression of CD46. PMID:11023821

Benefits and Risks for People and Livestock of Keeping Companion Animals: Searching for a Healthy Balance.

PubMed

Sterneberg-van der Maaten, T; Turner, D; Van Tilburg, J; Vaarten, J

2016-07-01

The mission of the CALLISTO (Companion Animals multisectoriaL interprofessionaL Interdisciplinary Strategic Think tank On zoonoses) project was to provide an overview of the current situation on the role of companion animals as a source of infectious diseases for people and food animals. It also aimed to identify knowledge and technology gaps for the most important zoonoses and propose targeted actions to reduce the risk of zoonotic diseases transmitted via companion animals. After a 3-year study, its members have developed practical recommendations for improved data collection on companion animal numbers and the mechanisms for disease surveillance in companion animals. They highlight the importance of introducing a system for the unique identification of dogs and other companion animals with an implanted microchip transponder and storage of the details it contains on an internationally accessible online database. Their report also emphasises the need for balanced communication with the public on the risks and benefits of pet ownership and the value of the 'One Health' concept to encourage closer collaboration between veterinary and human medical professionals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Transcription factor MITF and remodeller BRG1 define chromatin organisation at regulatory elements in melanoma cells.

PubMed

Laurette, Patrick; Strub, Thomas; Koludrovic, Dana; Keime, Céline; Le Gras, Stéphanie; Seberg, Hannah; Van Otterloo, Eric; Imrichova, Hana; Siddaway, Robert; Aerts, Stein; Cornell, Robert A; Mengus, Gabrielle; Davidson, Irwin

2015-03-24

Microphthalmia-associated transcription factor (MITF) is the master regulator of the melanocyte lineage. To understand how MITF regulates transcription, we used tandem affinity purification and mass spectrometry to define a comprehensive MITF interactome identifying novel cofactors involved in transcription, DNA replication and repair, and chromatin organisation. We show that MITF interacts with a PBAF chromatin remodelling complex comprising BRG1 and CHD7. BRG1 is essential for melanoma cell proliferation in vitro and for normal melanocyte development in vivo. MITF and SOX10 actively recruit BRG1 to a set of MITF-associated regulatory elements (MAREs) at active enhancers. Combinations of MITF, SOX10, TFAP2A, and YY1 bind between two BRG1-occupied nucleosomes thus defining both a signature of transcription factors essential for the melanocyte lineage and a specific chromatin organisation of the regulatory elements they occupy. BRG1 also regulates the dynamics of MITF genomic occupancy. MITF-BRG1 interplay thus plays an essential role in transcription regulation in melanoma.

Crystal structure, molecular docking, and biological activity of the zinc complexes with 2-thenoyltrifluoroacetone and N-donor heterocyclic ligands

NASA Astrophysics Data System (ADS)

Eshaghi Malekshah, Rahime; Salehi, Mehdi; Kubicki, Maciej; Khaleghian, Ali

2017-12-01

Two novel mononuclear complexes, [Zn (TTA) (bipy)Cl] (1) and [Zn (TTA) (phen)Cl] (2) (TTA = 4,4,4-Trifluoro-1-(2-furyl)-1,3-butanedione, phen = 1,10-phenanthroline and bipy 2, 2ʹ-bipyridine), were synthesized and fully characterized by elemental analyses, 1H NMR, UV-Vis, FTIR spectroscopy, and conductivity measurements. The crystal structures of these two mono-nuclear zinc (II) complexes were determined by X-ray single-crystal diffraction. The result of X-ray diffraction analyses revealed that both complexes have distorted tetragonal-pyramid structures. In MTT cytotoxicity studies, these Zn (II) complexes exhibited antitumor activity against MCF-7 and MKN-45 cell lines. It was also found that the proliferation rate of MCF-7 and MKN-45 cells decreased after treatment with the above-mentioned complexes. In addition, the apoptosis-inducing activity was assessed by AO/EB (Acridine Orange/Ethidium bromide) staining assay and found that they have the potential to act as effective metal-based anticancer drugs. Finally, the molecular docking studies showed that complex 2 strongly binds through minor groove with DNA by relative binding energy -7.33 kcal mol-1.