Use of the α-mannosidase I inhibitor kifunensine allows the crystallization of apo CTLA-4 homodimer produced in long-term cultures of Chinese hamster ovary cells

International Nuclear Information System (INIS)

Yu, Chao; Crispin, Max; Sonnen, Andreas F.-P.; Harvey, David J.; Chang, Veronica T.; Evans, Edward J.; Scanlan, Christopher N.; Stuart, David I.; Gilbert, Robert J. C.; Davis, Simon J.

2011-01-01

The α-mannosidase I inhibitor kifunensine inhibited N-glycan processing in long-term cultures of Chinese hamster ovary cells, allowing deglycosylation and crystallization of the homodimeric extracellular region of the inhibitory glycoprotein receptor CTLA-4 (CD152). Glycoproteins present problems for structural analysis since they often have to be glycosylated in order to fold correctly and because their chemical and conformational heterogeneity generally inhibits crystallization. It is shown that the α-mannosidase I inhibitor kifunensine, which has previously been used for the purpose of glycoprotein crystallization in short-term (3–5 d) cultures, is apparently stable enough to be used to produce highly endoglycosidase H-sensitive glycoprotein in long-term (3–4 week) cultures of stably transfected Chinese hamster ovary (CHO) cells. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry-based analysis of the extracellular region of the cytotoxic T-lymphocyte antigen 4 (CTLA-4; CD152) homodimer expressed in long-term CHO cell cultures in the presence of kifunensine revealed that the inhibitor restricted CTLA-4 glycan processing to Man 9 GlcNAc 2 and Man 5 GlcNAc 2 structures. Complex-type glycans were undetectable, suggesting that the inhibitor was active for the entire duration of the cultures. Endoglycosidase treatment of the homodimer yielded protein that readily formed orthorhombic crystals with unit-cell parameters a = 43.9, b = 51.5, c = 102.9 Å and space group P2 1 2 1 2 1 that diffracted to Bragg spacings of 1.8 Å. The results indicate that kifunensine will be effective in most, if not all, transient and long-term mammalian cell-based expression systems

Pre-exposure to moving form enhances static form sensitivity.

Directory of Open Access Journals (Sweden)

Thomas S A Wallis

Full Text Available BACKGROUND: Motion-defined form can seem to persist briefly after motion ceases, before seeming to gradually disappear into the background. Here we investigate if this subjective persistence reflects a signal capable of improving objective measures of sensitivity to static form. METHODOLOGY/PRINCIPAL FINDINGS: We presented a sinusoidal modulation of luminance, masked by a background noise pattern. The sinusoidal luminance modulation was usually subjectively invisible when static, but visible when moving. We found that drifting then stopping the waveform resulted in a transient subjective persistence of the waveform in the static display. Observers' objective sensitivity to the position of the static waveform was also improved after viewing moving waveforms, compared to viewing static waveforms for a matched duration. This facilitation did not occur simply because movement provided more perspectives of the waveform, since performance following pre-exposure to scrambled animations did not match that following pre-exposure to smooth motion. Observers did not simply remember waveform positions at motion offset, since removing the waveform before testing reduced performance. CONCLUSIONS/SIGNIFICANCE: Motion processing therefore interacts with subsequent static visual inputs in a way that can improve performance in objective sensitivity measures. We suggest that the brief subjective persistence of motion-defined forms that can occur after motion offsets is a consequence of the decay of a static form signal that has been transiently enhanced by motion processing.

APP Homodimers Transduce an Amyloid-β-Mediated Increase in Release Probability at Excitatory Synapses

Directory of Open Access Journals (Sweden)

Hilla Fogel

2014-06-01

Full Text Available Accumulation of amyloid-β peptides (Aβ, the proteolytic products of the amyloid precursor protein (APP, induces a variety of synaptic dysfunctions ranging from hyperactivity to depression that are thought to cause cognitive decline in Alzheimer’s disease. While depression of synaptic transmission has been extensively studied, the mechanisms underlying synaptic hyperactivity remain unknown. Here, we show that Aβ40 monomers and dimers augment release probability through local fine-tuning of APP-APP interactions at excitatory hippocampal boutons. Aβ40 binds to the APP, increases the APP homodimer fraction at the plasma membrane, and promotes APP-APP interactions. The APP activation induces structural rearrangements in the APP/Gi/o-protein complex, boosting presynaptic calcium flux and vesicle release. The APP growth-factor-like domain (GFLD mediates APP-APP conformational changes and presynaptic enhancement. Thus, the APP homodimer constitutes a presynaptic receptor that transduces signal from Aβ40 to glutamate release. Excessive APP activation may initiate a positive feedback loop, contributing to hippocampal hyperactivity in Alzheimer’s disease.

Origin of Asymmetric Charge Partitioning in the Dissociation of Gas-Phase Protein Homodimers

OpenAIRE

Jurchen, John C.; Williams, Evan R.

2003-01-01

The origin of asymmetric charge and mass partitioning observed for gas-phase dissociation of multiply charged macromolecular complexes has been hotly debated. These experiments hold the potential to provide detailed information about the interactions between the macromolecules within the complex. Here, this unusual phenomenon of asymmetric charge partitioning is investigated for several protein homodimers. Asymmetric charge partitioning in these ions depends on a number of factors, including ...

Chemical shift imprint of intersubunit communication in a symmetric homodimer

Science.gov (United States)

Falk, Bradley T.; Sapienza, Paul J.; Lee, Andrew L.

2016-01-01

Allosteric communication is critical for protein function and cellular homeostasis, and it can be exploited as a strategy for drug design. However, unlike many protein–ligand interactions, the structural basis for the long-range communication that underlies allostery is not well understood. This lack of understanding is most evident in the case of classical allostery, in which a binding event in one protomer is sensed by a second symmetric protomer. A primary reason why study of interdomain signaling is challenging in oligomeric proteins is the difficulty in characterizing intermediate, singly bound species. Here, we use an NMR approach to isolate and characterize a singly ligated state (“lig1”) of a homodimeric enzyme that is otherwise obscured by rapid exchange with apo and saturated forms. Mixed labeled dimers were prepared that simultaneously permit full population of the lig1 state and isotopic labeling of either protomer. Direct visualization of peaks from lig1 yielded site-specific ligand-state multiplets that provide a convenient format for assessing mechanisms of intersubunit communication from a variety of NMR measurements. We demonstrate this approach on thymidylate synthase from Escherichia coli, a homodimeric enzyme known to be half-the-sites reactive. Resolving the dUMP1 state shows that active site communication occurs not upon the first dUMP binding, but upon the second. Surprisingly, for many sites, dUMP1 peaks are found beyond the limits set by apo and dUMP2 peaks, indicating that binding the first dUMP pushes the enzyme ensemble to further conformational extremes than the apo or saturated forms. The approach used here should be generally applicable to homodimers. PMID:27466406

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

Directory of Open Access Journals (Sweden)

Michael B Tropak

2016-01-01

Full Text Available Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA. Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP, and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM, CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels.

Construction of a hybrid β-hexosaminidase subunit capable of forming stable homodimers that hydrolyze GM2 ganglioside in vivo

Science.gov (United States)

Tropak, Michael B; Yonekawa, Sayuri; Karumuthil-Melethil, Subha; Thompson, Patrick; Wakarchuk, Warren; Gray, Steven J; Walia, Jagdeep S; Mark, Brian L; Mahuran, Don

2016-01-01

Tay-Sachs or Sandhoff disease result from mutations in either the evolutionarily related HEXA or HEXB genes encoding respectively, the α- or β-subunits of β-hexosaminidase A (HexA). Of the three Hex isozymes, only HexA can interact with its cofactor, the GM2 activator protein (GM2AP), and hydrolyze GM2 ganglioside. A major impediment to establishing gene or enzyme replacement therapy based on HexA is the need to synthesize both subunits. Thus, we combined the critical features of both α- and β-subunits into a single hybrid µ-subunit that contains the α-subunit active site, the stable β-subunit interface and unique areas in each subunit needed to interact with GM2AP. To facilitate intracellular analysis and the purification of the µ-homodimer (HexM), CRISPR-based genome editing was used to disrupt the HEXA and HEXB genes in a Human Embryonic Kidney 293 cell line stably expressing the µ-subunit. In association with GM2AP, HexM was shown to hydrolyze a fluorescent GM2 ganglioside derivative both in cellulo and in vitro. Gene transfer studies in both Tay-Sachs and Sandhoff mouse models demonstrated that HexM expression reduced brain GM2 ganglioside levels. PMID:26966698

Probing intermolecular protein-protein interactions in the calcium-sensing receptor homodimer using bioluminescence resonance energy transfer (BRET)

DEFF Research Database (Denmark)

Jensen, Anders A.; Hansen, Jakob L; Sheikh, Søren P

2002-01-01

-induced intermolecular movements in the CaR homodimer using the new bioluminescence resonance energy transfer technique, BRET2, which is based on the transference of energy from Renilla luciferase (Rluc) to the green fluorescent protein mutant GFP2. We tagged CaR with Rluc and GFP2 at different intracellular locations...

Secreted Progranulin Is a Homodimer and Is Not a Component of High Density Lipoproteins (HDL)*

Science.gov (United States)

Nguyen, Andrew D.; Nguyen, Thi A.; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C.; Davidson, W. Sean; Farese, Robert V.

2013-01-01

Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170–180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180–190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL. PMID:23364791

Secreted progranulin is a homodimer and is not a component of high density lipoproteins (HDL).

Science.gov (United States)

Nguyen, Andrew D; Nguyen, Thi A; Cenik, Basar; Yu, Gang; Herz, Joachim; Walther, Tobias C; Davidson, W Sean; Farese, Robert V

2013-03-22

Progranulin is a secreted glycoprotein, and the GRN gene is mutated in some cases of frontotemporal dementia. Progranulin has also been implicated in cell growth, wound healing, inflammation, and cancer. We investigated the molecular nature of secreted progranulin and provide evidence that progranulin exists as a homodimer. Although recombinant progranulin has a molecular mass of ∼85 kDa by SDS-PAGE, it elutes in fractions corresponding to ∼170-180 kDa by gel-filtration chromatography. Additionally, recombinant progranulin can be intermolecularly cross-linked, yielding a complex corresponding to a dimer (∼180 kDa), and progranulins containing different epitope tags physically interact. In plasma, progranulin similarly forms complexes of ∼180-190 kDa. Although progranulin partially co-fractionated with high density lipoproteins (HDL) by gel-filtration chromatography, we found no evidence that progranulin in mouse or human plasma is a component of HDL either by ultracentrifugation or by lipid binding assays. We conclude that circulating progranulin exists as a dimer and is not likely a component of HDL.

Central nervous system vasculitis caused by propylthiouracil therapy: a case report and literature review.

Science.gov (United States)

Vanek, C; Samuels, M H

2005-01-01

Antineutrophil cytoplasmic antibodies (ANCA) are associated with vasculitis, including vasculitis induced by drugs such as the thionamides. The affected organ systems in thionamide-induced vasculitis have been primarily renal, musculoskeletal, and dermatologic. We describe the first case of thionamide-induced central nervous system vasculitis presenting as confusion, with complete resolution after discontinuation of propylthiouracil. We review the literature and summarize 42 additional cases of thionamide-induced ANCA-positive vasculitis since 1992. Propylthiouracil was responsible in 93% of cases and the predominant ANCA pattern on immunofluorescent staining was perinuclear (p-ANCA). Clinical improvement occurred after drug discontinuation in 93%, steroid therapy was used in some cases. The mean duration of treatment with thionamides was 35 months prior to presentation. Long-term medical treatment with thionamides for hyperthyroidism may increase the risk of this severe side effect.

Plasmon-mediated binding forces on gold or silver homodimer and heterodimer

International Nuclear Information System (INIS)

Liaw, Jiunn-Woei; Kuo, Ting-Yu; Kuo, Mao-Kuen

2016-01-01

This study theoretically investigates plasmon-mediated optical binding forces, which are exerted on metal homo or heterodimers, induced by the normal illumination of a linearly polarized plane wave or Gaussian beam. Using the multiple multipole method, we analyzed the optical force in terms of Maxwell's stress tensor for various interparticle distance at some specific wavelengths. Numerical results show that for a given wavelength there are several stable equilibrium distances between two nanoparticles (NPs) of a homodimer, which are slightly shorter than some integer multiples of the wavelength in medium, such that metal dimer acts as bonded together. At these specific interparticle distances, the optical force between dimer is null and serves a restoring force, which is repulsive and attractive, respectively, as the two NPs are moving closer to and away from each other. The spring constant of the restoring force at the first stable equilibrium is always the largest, indicating that the first stable equilibrium distance is the most stable one. Moreover, the central line (orientation) of a dimer tends to be perpendicular to the polarization of light. For the cases of heterodimers, the phenomenon of stable equilibrium interparticle distance still exists, except there is an extra net photophoretic force drifting the heterodimer as one. Moreover, gradient force provided by a Gaussian beam may reduce the stability of these equilibriums, so larger NPs are preferred to stabilize a dimer under illumination of Gaussian beam. The finding may pave the way for using optical manipulation on the gold or silver colloidal self-assembly. - Highlights: • Optical binding force on Au/Ag dimer by linearly polarized light is studied. • For a wavelength several stable equilibriums for homodimer bound together exist. • The central line of a dimer tends to be perpendicular to the polarization of light. • For a heterodimer, stable equilibriums still exist with a net photophoretic

The asymmetric binding of PGC-1α to the ERRα and ERRγ nuclear receptor homodimers involves a similar recognition mechanism.

Directory of Open Access Journals (Sweden)

Maria Takacs

Full Text Available PGC-1α is a crucial regulator of cellular metabolism and energy homeostasis that functionally acts together with the estrogen-related receptors (ERRα and ERRγ in the regulation of mitochondrial and metabolic gene networks. Dimerization of the ERRs is a pre-requisite for interactions with PGC-1α and other coactivators, eventually leading to transactivation. It was suggested recently (Devarakonda et al that PGC-1α binds in a strikingly different manner to ERRγ ligand-binding domains (LBDs compared to its mode of binding to ERRα and other nuclear receptors (NRs, where it interacts directly with the two ERRγ homodimer subunits.Here, we show that PGC-1α receptor interacting domain (RID binds in an almost identical manner to ERRα and ERRγ homodimers. Microscale thermophoresis demonstrated that the interactions between PGC-1α RID and ERR LBDs involve a single receptor subunit through high-affinity, ERR-specific L3 and low-affinity L2 interactions. NMR studies further defined the limits of PGC-1α RID that interacts with ERRs. Consistent with these findings, the solution structures of PGC-1α/ERRα LBDs and PGC-1α/ERRγ LBDs complexes share an identical architecture with an asymmetric binding of PGC-1α to homodimeric ERR.These studies provide the molecular determinants for the specificity of interactions between PGC-1α and the ERRs, whereby negative cooperativity prevails in the binding of the coactivators to these receptors. Our work indicates that allosteric regulation may be a general mechanism controlling the binding of the coactivators to homodimers.

HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats.

Directory of Open Access Journals (Sweden)

Osiris Marroquin Belaunzaran

Full Text Available HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA. HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272 and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS patients and HLA-B27 transgenic rats. We characterized a novel B272-specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders.The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry.HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM. HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules.HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders.

HLA-B27-Homodimer-Specific Antibody Modulates the Expansion of Pro-Inflammatory T-Cells in HLA-B27 Transgenic Rats

Science.gov (United States)

Marroquin Belaunzaran, Osiris; Kleber, Sascha; Schauer, Stefan; Hausmann, Martin; Nicholls, Flora; Van den Broek, Maries; Payeli, Sravan; Ciurea, Adrian; Milling, Simon; Stenner, Frank; Shaw, Jackie; Kollnberger, Simon; Bowness, Paul; Petrausch, Ulf; Renner, Christoph

2015-01-01

Objectives HLA-B27 is a common genetic risk factor for the development of Spondyloarthritides (SpA). HLA-B27 can misfold to form cell-surface heavy chain homodimers (B272) and induce pro-inflammatory responses that may lead to SpA pathogenesis. The presence of B272 can be detected on leukocytes of HLA-B27+ Ankylosing spondylitis (AS) patients and HLA-B27 transgenic rats. We characterized a novel B272–specific monoclonal antibody to study its therapeutic use in HLA-B27 associated disorders. Methods The monoclonal HD5 antibody was selected from a phage library to target cell-surface B272 homodimers and characterized for affinity, specificity and ligand binding. The immune modulating effect of HD5 was tested in HLA-B27 transgenic rats. Onset and progression of disease profiles were monitored during therapy. Cell-surface B272 and expansion of pro-inflammatory cells from blood, spleen and draining lymph nodes were assessed by flow cytometry. Results HD5 bound B272 with high specificity and affinity (Kd = 0.32 nM). HD5 blocked cell-surface interaction of B272 with immune regulatory receptors KIR3DL2, LILRB2 and Pirb. In addition, HD5 modulated the production of TNF from CD4+ T-cells by limiting B272 interactions in vitro. In an HLA-B27 transgenic rat model repetitive dosing of HD5 reduced the expansion of pro-inflammatory CD4+ T-cells, and decreased the levels of soluble TNF and number of cell-surface B272 molecules. Conclusion HD5 predominantly inhibits early TNF production and expansion of pro-inflammatory CD4+ T-cells in HLA-B27 transgenic rats. Monoclonal antibodies targeting cell-surface B272 propose a new concept for the modulation of inflammatory responses in HLA-B27 related disorders. PMID:26125554

Surface sensitivity of nuclear-knock-out form factors

International Nuclear Information System (INIS)

Fratamico, G.

1984-01-01

A numerical calculation has been performed to investigate the sensitivity of nuclear-knock-out form factors to nuclear-surface behaviour of bound-state wave functions. The result of our investigation suggests that one can extract the bound-state behaviour at the surface from experimental information on nuclear-knock-out form factors

Optical determination of the electronic coupling and intercalation geometry of thiazole orange homodimer in DNA

Science.gov (United States)

Cunningham, Paul D.; Bricker, William P.; Díaz, Sebastián A.; Medintz, Igor L.; Bathe, Mark; Melinger, Joseph S.

2017-08-01

Sequence-selective bis-intercalating dyes exhibit large increases in fluorescence in the presence of specific DNA sequences. This property makes this class of fluorophore of particular importance to biosensing and super-resolution imaging. Here we report ultrafast transient anisotropy measurements of resonance energy transfer (RET) between thiazole orange (TO) molecules in a complex formed between the homodimer TOTO and double-stranded (ds) DNA. Biexponential homo-RET dynamics suggest two subpopulations within the ensemble: 80% intercalated and 20% non-intercalated. Based on the application of the transition density cube method to describe the electronic coupling and Monte Carlo simulations of the TOTO/dsDNA geometry, the dihedral angle between intercalated TO molecules is estimated to be 81° ± 5°, corresponding to a coupling strength of 45 ± 22 cm-1. Dye intercalation with this geometry is found to occur independently of the underlying DNA sequence, despite the known preference of TOTO for the nucleobase sequence CTAG. The non-intercalated subpopulation is inferred to have a mean inter-dye separation distance of 19 Å, corresponding to coupling strengths between 0 and 25 cm-1. This information is important to enable the rational design of energy transfer systems that utilize TOTO as a relay dye. The approach used here is generally applicable to determining the electronic coupling strength and intercalation configuration of other dimeric bis-intercalators.

The human dopamine transporter forms a tetramer in the plasma membrane: cross-linking of a cysteine in the fourth transmembrane segment is sensitive to cocaine analogs.

Science.gov (United States)

Hastrup, Hanne; Sen, Namita; Javitch, Jonathan A

2003-11-14

Using cysteine cross-linking, we demonstrated previously that the dopamine transporter (DAT) is at least a homodimer, with the extracellular end of transmembrane segment (TM) 6 at a symmetrical dimer interface. We have now explored the possibility that DAT exists as a higher order oligomer in the plasma membrane. Cysteine cross-linking of wild type DAT resulted in bands on SDS-PAGE consistent with dimer, trimer, and tetramer, suggesting that DAT forms a tetramer in the plasma membrane. A cysteine-depleted DAT (CD-DAT) into which only Cys243 or Cys306 was reintroduced was cross-linked to dimer, suggesting that these endogenous cysteines in TM4 and TM6, respectively, were cross-linked at a symmetrical dimer interface. Reintroduction of both Cys243 and Cys306 into CD-DAT led to a pattern of cross-linking indistinguishable from that of wild type, with dimer, trimer, and tetramer bands. This indicated that the TM4 interface and the TM6 interface are distinct and further suggested that DAT may exist in the plasma membrane as a dimer of dimers, with two symmetrical homodimer interfaces. The cocaine analog MFZ 2-12 and other DAT inhibitors, including benztropine and mazindol, protected Cys243 against cross-linking. In contrast, two substrates of DAT, dopamine and tyramine, did not significantly impact cross-linking. We propose that the impairment of cross-linking produced by the inhibitors results from a conformational change at the TM4 interface, further demonstrating that these compounds are not neutral blockers but by themselves have effects on the structure of the transporter.

Homodimers of Vanillin and Apocynin Decrease the Metastatic Potential of Human Cancer Cells by Inhibiting the FAK/PI3K/Akt Signaling Pathway.

Science.gov (United States)

Jantaree, Phatcharida; Lirdprapamongkol, Kriengsak; Kaewsri, Wilailak; Thongsornkleeb, Charnsak; Choowongkomon, Kiattawee; Atjanasuppat, Korakot; Ruchirawat, Somsak; Svasti, Jisnuson

2017-03-22

The spread of cancer cells to distant organs, in a process called metastasis, is the main factor that contributes to most death in cancer patients. Vanillin, the vanilla flavoring agent, has been shown to suppress metastasis in a mouse model. Here, we evaluated the antimetastatic potential of the food additive divanillin, the homodimer of vanillin, and their structurally related compounds, apocynin and diapocynin, in hepatocellular carcinoma cells. The Transwell invasion assay showed that the dimeric forms exhibited a potency higher than those of vanillin and apocynin in inhibiting invasion, with IC 50 values of 23.3 ± 7.4 to 41.3 ± 4.2 μM for the dimers, which are 26-34-fold lower than IC 50 values of vanillin and apocynin (p vanillin and apocynin to the Y397 pocket of the FAK FERM domain. Thus, the food additive divanillin has antimetastatic potential greater than that of the flavoring agent vanillin.

An update on the medical treatment of Graves' hyperthyroidism.

Science.gov (United States)

Marinò, Michele; Latrofa, Francesco; Menconi, Francesca; Chiovato, Luca; Vitti, Paolo

2014-11-01

Medical treatment of Graves' hyperthyroidism is based on the use of thionamides; namely, methimazole and propylthiouracil. In the past, methimazole was preferred by European endocrinologists, whereas propylthiouracil was the first choice for the majority of their North American colleagues. However, because of the recent definition of a better side-effect profile, methimazole is nowadays the first choice world while. Although thionamides are quite effective for the short-term control of Graves' hyperthyroidism, a relatively high proportion of patients relapses after thionamide withdrawal. Other possible medical treatments, include iodine and compounds containing iodine, perchlorate, lithium (as an adjuvant in patients undergoing radioiodine therapy), β-adrenergic antagonists, glucocorticoids, and some new molecules still under investigation. Management of Graves' hyperthyroidism using thionamides as well as the other available medical treatments is here reviewed in detail, with a special mention of situations such as pregnancy and lactation, as well as neonatal and fetal thyrotoxicosis.

A report of three cases of jaundice with thyrotoxicosis.

Science.gov (United States)

Akande, T O; Balogun, W O

2013-09-01

Jaundice and hepatic dysfunction have been reported in patients with thyrotoxicosis and could be due to different mechanisms. To describe three cases of jaundice occurring in patients with thyrotoxicosis and to illustrate the importance of early institution of thionamides when indicated. We present the clinical and laboratory features of three patients presenting within a year with thyrotoxicosis and jaundice and whose clinical conditions improved remarkably following treatment with thionamides. In addition, current literature on the subject is reviewed and summarised. The three patients presented with goitre and jaundice. None of the patients had received blood products, undergone scarification markings or experienced any previous episode of jaundice. Thyroid function tests in the three patients were consistent with a diagnosis of thyrotoxicosis. Liver function tests showed elevated bilirubin and transaminases. All patients improved remarkably following treatment with thionamides. It is important to rule out thyrotoxicosis in patients with jaundice of unknown cause and consider early use of thionamides for treatment of the thyrotoxicosis, if confirmed.

Considering the edge-crack sensitivity of a hot-rolled steel in forming simulation

Science.gov (United States)

Gläsner, T.; Schneider, M.; Troitzsch, M.; Westhäuser, S.

2016-11-01

The formability of sheet metal materials is locally reduced by shear cutting operations, and as a result the risk of a crack during further processing is increased at the edge. Materials particularly susceptible to this are described as sensitive to edge-cracking. A procedure for quantitatively determining edge-crack sensitivity and for applying corresponding characteristic values has not been previously established. Below, two test methods and an approach for using the results in an extended forming limit diagram are presented. The producibility of a collar drawn test component as well as a chassis component is reevaluated using this extended forming limit diagram.

The neonatal Fc receptor (FcRn) binds independently to both sites of the IgG homodimer with identical affinity.

Science.gov (United States)

Abdiche, Yasmina Noubia; Yeung, Yik Andy; Chaparro-Riggers, Javier; Barman, Ishita; Strop, Pavel; Chin, Sherman Michael; Pham, Amber; Bolton, Gary; McDonough, Dan; Lindquist, Kevin; Pons, Jaume; Rajpal, Arvind

2015-01-01

The neonatal Fc receptor (FcRn) is expressed by cells of epithelial, endothelial and myeloid lineages and performs multiple roles in adaptive immunity. Characterizing the FcRn/IgG interaction is fundamental to designing therapeutic antibodies because IgGs with moderately increased binding affinities for FcRn exhibit superior serum half-lives and efficacy. It has been hypothesized that 2 FcRn molecules bind an IgG homodimer with disparate affinities, yet their affinity constants are inconsistent across the literature. Using surface plasmon resonance biosensor assays that eliminated confounding experimental artifacts, we present data supporting an alternate hypothesis: 2 FcRn molecules saturate an IgG homodimer with identical affinities at independent sites, consistent with the symmetrical arrangement of the FcRn/Fc complex observed in the crystal structure published by Burmeister et al. in 1994. We find that human FcRn binds human IgG1 with an equilibrium dissociation constant (KD) of 760 ± 60 nM (N = 14) at 25°C and pH 5.8, and shows less than 25% variation across the other human subtypes. Human IgG1 binds cynomolgus monkey FcRn with a 2-fold higher affinity than human FcRn, and binds both mouse and rat FcRn with a 10-fold higher affinity than human FcRn. FcRn/IgG interactions from multiple species show less than a 2-fold weaker affinity at 37°C than at 25°C and appear independent of an IgG's variable region. Our in vivo data in mouse and rat models demonstrate that both affinity and avidity influence an IgG's serum half-life, which should be considered when choosing animals, especially transgenic systems, as surrogates.

Binding of superantigen toxins into the CD28 homodimer interface is essential for induction of cytokine genes that mediate lethal shock.

Directory of Open Access Journals (Sweden)

Gila Arad

2011-09-01

Full Text Available Bacterial superantigens, a diverse family of toxins, induce an inflammatory cytokine storm that can lead to lethal shock. CD28 is a homodimer expressed on T cells that functions as the principal costimulatory ligand in the immune response through an interaction with its B7 coligands, yet we show here that to elicit inflammatory cytokine gene expression and toxicity, superantigens must bind directly into the dimer interface of CD28. Preventing access of the superantigen to CD28 suffices to block its lethality. Mice were protected from lethal superantigen challenge by short peptide mimetics of the CD28 dimer interface and by peptides selected to compete with the superantigen for its binding site in CD28. Superantigens use a conserved β-strand/hinge/α-helix domain of hitherto unknown function to engage CD28. Mutation of this superantigen domain abolished inflammatory cytokine gene induction and lethality. Structural analysis showed that when a superantigen binds to the T cell receptor on the T cell and major histocompatibility class II molecule on the antigen-presenting cell, CD28 can be accommodated readily as third superantigen receptor in the quaternary complex, with the CD28 dimer interface oriented towards the β-strand/hinge/α-helix domain in the superantigen. Our findings identify the CD28 homodimer interface as a critical receptor target for superantigens. The novel role of CD28 as receptor for a class of microbial pathogens, the superantigen toxins, broadens the scope of pathogen recognition mechanisms.

Phage type and sensitivity to antibiotics of Staphylococcus aureus film-forming strains isolated from airway mucosa

Directory of Open Access Journals (Sweden)

O. S. Voronkova

2014-10-01

Full Text Available Today film-forming strains of bacteria play very important role in clinical pathology. Staphylococci are ones of most dangerous of them. This bacteria can determine different pathological processes, for example, complication of airway mucosa. The ability to form a biofilm is one of the main properties of nosocomial strains. These strains should be monitored and their carriers are to be properly treated. To determine the origin of staphylococci strains we used bacteriophages from the International kit. The aim of research was to determine the phage type of staphylococci film-forming strains, that were isolated from naso-pharingial mucosa. Phage typing has been carried out for 16 film-forming strains of S. aureus. To solve this problem, we used the International phage kit by Fisher’s method. As a result, sensitivity to phages from the International kit showed 53.8% of studied strains of S. aureus. 64.3% of sensitivity strains were lysed by one of the phage, 21.4% – were by two of the phages, 14.3% – by three of the phages. Isolates were sensitive to phages: 81 – 42.9%, 75 – 35.7%, 28.6% were sensitive to phages 47 and 53. All cases of detection of sensitivity to phage 47 coincided with the ability to form biofilm. Among non-film-forming strains there was no sensitive strains for this phage. Film-forming strains resist to erythromycin (62.5%, ciprofloxacin (43.8%, gentamicin (56.3%, tetracycline (87.5%, amoxicillin (93.8%, and cefuroxime (37.5%. All cases of sensitivity to phage 47 coincided with resistance to erythromycin, amoxicillin and tetracycline. For two of these strains, we also defined resistance to gentamicin and for one of them – to ciprofloxacin. Results of research allowed to relate the bacterial cultures for determining the type. This may have implications for studying of film-forming ability, because surface structures of bacterial cell take place in this process. Belonging of an isolate to specific phage type may

Densified waste form and method for forming

Science.gov (United States)

Garino, Terry J.; Nenoff, Tina M.; Sava Gallis, Dorina Florentina

2015-08-25

Materials and methods of making densified waste forms for temperature sensitive waste material, such as nuclear waste, formed with low temperature processing using metallic powder that forms the matrix that encapsulates the temperature sensitive waste material. The densified waste form includes a temperature sensitive waste material in a physically densified matrix, the matrix is a compacted metallic powder. The method for forming the densified waste form includes mixing a metallic powder and a temperature sensitive waste material to form a waste form precursor. The waste form precursor is compacted with sufficient pressure to densify the waste precursor and encapsulate the temperature sensitive waste material in a physically densified matrix.

Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

KAUST Repository

Cheung, Lydia W T; Walkiewicz, Katarzyna Wiktoria; Besong, Tabot M.D.; Guo, Huifang; Hawke, David H.; Arold, Stefan T.; Mills, Gordon B.

2015-01-01

The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomerdimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development. © Cheung et al.

Regulation of the PI3K pathway through a p85α monomer–homodimer equilibrium

KAUST Repository

Cheung, Lydia W T

2015-07-29

The canonical action of the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI3K) is to associate with the p110α catalytic subunit to allow stimuli-dependent activation of the PI3K pathway. We elucidate a p110α-independent role of homodimerized p85α in the positive regulation of PTEN stability and activity. p110α-free p85α homodimerizes via two intermolecular interactions (SH3:proline-rich region and BH:BH) to selectively bind unphosphorylated activated PTEN. As a consequence, homodimeric but not monomeric p85α suppresses the PI3K pathway by protecting PTEN from E3 ligase WWP2-mediated proteasomal degradation. Further, the p85α homodimer enhances the lipid phosphatase activity and membrane association of PTEN. Strikingly, we identified cancer patient-derived oncogenic p85α mutations that target the homodimerization or PTEN interaction surface. Collectively, our data suggest the equilibrium of p85α monomerdimers regulates the PI3K pathway and disrupting this equilibrium could lead to disease development. © Cheung et al.

Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

KAUST Repository

Xiao, Xi; de Bettignies, Thibaut; Olsen, Ylva S.; Agusti, Susana; Duarte, Carlos M.; Wernberg, Thomas

2015-01-01

Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

Sensitivity and Acclimation of Three Canopy-Forming Seaweeds to UVB Radiation and Warming

KAUST Repository

Xiao, Xi

2015-12-02

Canopy-forming seaweeds, as primary producers and foundation species, provide key ecological services. Their responses to multiple stressors associated with climate change could therefore have important knock-on effects on the functioning of coastal ecosystems. We examined interactive effects of UVB radiation and warming on juveniles of three habitat-forming subtidal seaweeds from Western Australia–Ecklonia radiata, Scytothalia dorycarpa and Sargassum sp. Fronds were incubated for 14 days at 16–30°C with or without UVB radiation and growth, health status, photosynthetic performance, and light absorbance measured. Furthermore, we used empirical models from the metabolic theory of ecology to evaluate the sensitivity of these important seaweeds to ocean warming. Results indicated that responses to UVB and warming were species specific, with Sargassum showing highest tolerance to a broad range of temperatures. Scytothalia was most sensitive to elevated temperature based on the reduced maximum quantum yields of PSII; however, Ecklonia was most sensitive, according to the comparison of activation energy calculated from Arrhenius’ model. UVB radiation caused reduction in the growth, physiological responses and thallus health in all three species. Our findings indicate that Scytothalia was capable of acclimating in response to UVB and increasing its light absorption efficiency in the UV bands, probably by up-regulating synthesis of photoprotective compounds. The other two species did not acclimate over the two weeks of exposure to UVB. Overall, UVB and warming would severely inhibit the growth and photosynthesis of these canopy-forming seaweeds and decrease their coverage. Differences in the sensitivity and acclimation of major seaweed species to temperature and UVB may alter the balance between species in future seaweed communities under climate change.

Self-homodimerization of an actinoporin by disulfide bridging reveals implications for their structure and pore formation.

Science.gov (United States)

Valle, Aisel; Pérez-Socas, Luis Benito; Canet, Liem; Hervis, Yadira de la Patria; de Armas-Guitart, German; Martins-de-Sa, Diogo; Lima, Jônatas Cunha Barbosa; Souza, Adolfo Carlos Barros; Barbosa, João Alexandre Ribeiro Gonçalves; de Freitas, Sonia Maria; Pazos, Isabel Fabiola

2018-04-26

The Trp111 to Cys mutant of sticholysin I, an actinoporin from Stichodactyla helianthus sea anemone, forms a homodimer via a disulfide bridge. The purified dimer is 193 times less hemolytic than the monomer. Ultracentrifugation, dynamic light scattering and size-exclusion chromatography demonstrate that monomers and dimers are the only independent oligomeric states encountered. Indeed, circular dichroism and fluorescence spectroscopies showed that Trp/Tyr residues participate in homodimerization and that the dimer is less thermostable than the monomer. A homodimer three-dimensional model was constructed and indicates that Trp147/Tyr137 are at the homodimer interface. Spectroscopy results validated the 3D-model and assigned 85° to the disulfide bridge dihedral angle responsible for dimerization. The homodimer model suggests that alterations in the membrane/carbohydrate-binding sites in one of the monomers, as result of dimerization, could explain the decrease in the homodimer ability to form pores.

Role of α-Helical Structure in Organic Solvent-Activated Homodimer of Elastase Strain K

Directory of Open Access Journals (Sweden)

Chee Fah Wong

2011-09-01

Full Text Available Recombinant elastase strain K overexpressed from E. coli KRX/pCon2(3 was purified to homogeneity by a combination of hydrophobic interaction chromatography and ion exchange chromatography, with a final yield of 48% and a 25-fold increase in specific activity. The purified protein had exhibited a first ever reported homodimer size of 65 kDa by SDS-PAGE and MALDI-TOF, a size which is totally distinct from that of typically reported 33 kDa monomer from P. aeruginosa. The organic solvent stability experiment had demonstrated a stability pattern which completely opposed the rules laid out in previous reports in which activity stability and enhancement were observed in hydrophilic organic solvents such as DMSO, methanol, ethanol and 1-propanol. The high stability and enhancement of the enzyme in hydrophilic solvents were explained from the view of alteration in secondary structures. Elastinolytic activation and stability were observed in 25 and 50% of methanol, respectively, despite slight reduction in α-helical structure caused upon the addition of the solvent. Further characterization experiments had postulated great stability and enhancement of elastase strain K in broad range of temperatures, pHs, metal ions, surfactants, denaturing agents and substrate specificity, indicating its potential application in detergent formulation.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB1 cannabinoid receptors

International Nuclear Information System (INIS)

Jäntti, Maria H.; Mandrika, Ilona; Kukkonen, Jyrki P.

2014-01-01

Highlights: • OX 1 and OX 2 orexin and CB 1 cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX 1 orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB 1 cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX 1 , OX 2 and CB 1 receptors, C-terminally fused with either Renilla luciferase or GFP 2 green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB 1 receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP 2 to CB 1 produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX 1 –OX 2 interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB 1 receptors, dimerization could be an effective way of forming signal complexes with optimal cannabinoid concentrations

Multimodal Nonlinear Optical Imaging for Sensitive Detection of Multiple Pharmaceutical Solid-State Forms and Surface Transformations.

Science.gov (United States)

Novakovic, Dunja; Saarinen, Jukka; Rojalin, Tatu; Antikainen, Osmo; Fraser-Miller, Sara J; Laaksonen, Timo; Peltonen, Leena; Isomäki, Antti; Strachan, Clare J

2017-11-07

Two nonlinear imaging modalities, coherent anti-Stokes Raman scattering (CARS) and sum-frequency generation (SFG), were successfully combined for sensitive multimodal imaging of multiple solid-state forms and their changes on drug tablet surfaces. Two imaging approaches were used and compared: (i) hyperspectral CARS combined with principal component analysis (PCA) and SFG imaging and (ii) simultaneous narrowband CARS and SFG imaging. Three different solid-state forms of indomethacin-the crystalline gamma and alpha forms, as well as the amorphous form-were clearly distinguished using both approaches. Simultaneous narrowband CARS and SFG imaging was faster, but hyperspectral CARS and SFG imaging has the potential to be applied to a wider variety of more complex samples. These methodologies were further used to follow crystallization of indomethacin on tablet surfaces under two storage conditions: 30 °C/23% RH and 30 °C/75% RH. Imaging with (sub)micron resolution showed that the approach allowed detection of very early stage surface crystallization. The surfaces progressively crystallized to predominantly (but not exclusively) the gamma form at lower humidity and the alpha form at higher humidity. Overall, this study suggests that multimodal nonlinear imaging is a highly sensitive, solid-state (and chemically) specific, rapid, and versatile imaging technique for understanding and hence controlling (surface) solid-state forms and their complex changes in pharmaceuticals.

BECN2 interacts with ATG14 through a metastable coiled-coil to mediate autophagy: BECN2 CCD Structure and Interaction with ATG14

Energy Technology Data Exchange (ETDEWEB)

Su, Minfei; Li, Yue; Wyborny, Shane; Neau, David; Chakravarthy, Srinivas; Levine, Beth; Colbert, Christopher L.; Sinha, Sangita C. (NDSU); (IIT); (Cornell); (UTSMC)

2017-03-12

ATG14 binding to BECN/Beclin homologs is essential for autophagy, a critical catabolic homeostasis pathway. Here, we show that the α-helical, coiled-coil domain (CCD) of BECN2, a recently identified mammalian BECN1 paralog, forms an antiparallel, curved homodimer with seven pairs of nonideal packing interactions, while the BECN2 CCD and ATG14 CCD form a parallel, curved heterodimer stabilized by multiple, conserved polar interactions. Compared to BECN1, the BECN2 CCD forms a weaker homodimer, but binds more tightly to the ATG14 CCD. Mutation of nonideal BECN2 interface residues to more ideal pairs improves homodimer self-association and thermal stability. Unlike BECN1, all BECN2 CCD mutants bind ATG14, although more weakly than wild type. Thus, polar BECN2 CCD interface residues result in a metastable homodimer, facilitating dissociation, but enable better interactions with polar ATG14 residues stabilizing the BECN2:ATG14 heterodimer. These structure-based mechanistic differences in BECN1 and BECN2 homodimerization and heterodimerization likely dictate competitive ATG14 recruitment.

The NF-κB p65 and p50 homodimer cooperate with IRF8 to activate iNOS transcription

International Nuclear Information System (INIS)

Simon, Priscilla S.; Sharman, Sarah K.; Lu, Chunwan; Yang, Dafeng; Paschall, Amy V.; Tulachan, Sidhartha S.; Liu, Kebin

2015-01-01

observed that the p65/p65 and p50/p50 homodimers, not the canonical p65/p50 heterodimer, directly binds to the nos2 promoter to regulate iNOS expression in myeloid cells. IFNγ-induced IRF8 acts in concert with NF-κB to regulate iNOS expression in both colon carcinoma and myeloid cells. In myeloid cells, the NF-κB complexes that bind to the nos2 promoter are p65/p65 and p50/p50 homodimers

Expression, purification, crystallization and preliminary X-ray diffraction analysis of rhesus macaque CD8αα homodimer

International Nuclear Information System (INIS)

Zong, Lili; Chen, Yong; Yan, Jinghua; Zhang, Jianhua

2010-01-01

CD8α exodomain protein, a crucial immune-system factor in rhesus macaque (M. mulatta), one of the best animal models for vaccine design, was assembled and crystallized. The full structure data will contribute to future studies of immune responses in rhesus macaques. As a T-cell co-receptor, CD8 binds to MHC class I molecules and plays a pivotal role in the activation of cytotoxic T lymphocytes. To date, structures of CD8 have been solved for two different mammals: human and mouse. The infection of rhesus macaques (Macaca mulatta) by simian immunodeficiency virus (SIV) is the best animal model for studying HIV. In this study, the rhesus macaque CD8 (rCD8) αα homodimer was obtained and rCD8α exodomain protein crystals were successfully obtained for further structural analysis. Diffraction data were collected to a resolution of 2.4 Å. The crystal belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 46.52, b = 56.28, c = 82.40 Å. These data will facilitate further studies on the structural differences between these CD8 structures and the cellular immune responses of rhesus macaque

Assembly and Molecular Architecture of the Phosphoinositide 3-Kinase p85α Homodimer.

Science.gov (United States)

LoPiccolo, Jaclyn; Kim, Seung Joong; Shi, Yi; Wu, Bin; Wu, Haiyan; Chait, Brian T; Singer, Robert H; Sali, Andrej; Brenowitz, Michael; Bresnick, Anne R; Backer, Jonathan M

2015-12-18

Phosphoinositide 3-kinases (PI3Ks) are a family of lipid kinases that are activated by growth factor and G-protein-coupled receptors and propagate intracellular signals for growth, survival, proliferation, and metabolism. p85α, a modular protein consisting of five domains, binds and inhibits the enzymatic activity of class IA PI3K catalytic subunits. Here, we describe the structural states of the p85α dimer, based on data from in vivo and in vitro solution characterization. Our in vitro assembly and structural analyses have been enabled by the creation of cysteine-free p85α that is functionally equivalent to native p85α. Analytical ultracentrifugation studies showed that p85α undergoes rapidly reversible monomer-dimer assembly that is highly exothermic in nature. In addition to the documented SH3-PR1 dimerization interaction, we identified a second intermolecular interaction mediated by cSH2 domains at the C-terminal end of the polypeptide. We have demonstrated in vivo concentration-dependent dimerization of p85α using fluorescence fluctuation spectroscopy. Finally, we have defined solution conditions under which the protein is predominantly monomeric or dimeric, providing the basis for small angle x-ray scattering and chemical cross-linking structural analysis of the discrete dimer. These experimental data have been used for the integrative structure determination of the p85α dimer. Our study provides new insight into the structure and assembly of the p85α homodimer and suggests that this protein is a highly dynamic molecule whose conformational flexibility allows it to transiently associate with multiple binding proteins. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

EU-approved rapid tests for bovine spongiform encephalopathy detect atypical forms: a study for their sensitivities.

Directory of Open Access Journals (Sweden)

Daniela Meloni

Full Text Available Since 2004 it become clear that atypical bovine spongiform encephalopthies (BSEs exist in cattle. Whenever their detection has relied on active surveillance plans implemented in Europe since 2001 by rapid tests, the overall and inter-laboratory performance of these diagnostic systems in the detection of the atypical strains has not been studied thoroughly to date. To fill this gap, the present study reports on the analytical sensitivity of the EU-approved rapid tests for atypical L- and H-type and classical BSE in parallel. Each test was challenged with two dilution series, one created from a positive pool of the three BSE forms according to the EURL standard method of homogenate preparation (50% w/v and the other as per the test kit manufacturer's instructions. Multilevel logistic models and simple logistic models with the rapid test as the only covariate were fitted for each BSE form analyzed as directed by the test manufacturer's dilution protocol. The same schemes, but excluding the BSE type, were then applied to compare test performance under the manufacturer's versus the water protocol. The IDEXX HerdChek ® BSE-scrapie short protocol test showed the highest sensitivity for all BSE forms. The IDEXX® HerdChek BSE-scrapie ultra short protocol, the Prionics®--Check WESTERN and the AJ Roboscreen® BetaPrion tests showed similar sensitivities, followed by the Roche® PrionScreen, the Bio-Rad® TeSeE™ SAP and the Prionics®--Check PrioSTRIP in descending order of analytical sensitivity. Despite these differences, the limit of detection of all seven rapid tests against the different classes of material set within a 2 log(10 range of the best-performing test, thus meeting the European Food Safety Authority requirement for BSE surveillance purposes. These findings indicate that not many atypical cases would have been missed surveillance since 2001 which is important for further epidemiological interpretations of the sporadic character of

Sensitivity to ultraviolet radiation in a dominantly inherited form of xeroderma pigmentosum

International Nuclear Information System (INIS)

Imray, F.P.; Relf, W.; Ramsay, R.G.; Kidson, C.; Hockey, A.

1986-01-01

An Australian family is described in which a mild form of xeroderma pigmentosum (XP) is inherited as an autosomal dominant trait. Studies of lymphoblastoid cells and fibroblasts from affected person demonstrated sensitivity to ultraviolet (UV) light as judged by diminished clonogenicity and higher frequencies of UV induced chromosome aberrations compared to normal controls. After UV irradiation of dominant XP cells, replicative DNA synthesis was depressed to a greater extent than normal and the level of UV induced DNA repair synthesis was lower than that in normal cells. The level of sister chromatid exchanges and the numbers of 6-thioguanine resistant mutants induced by UV irradiation were equal to those found in normal controls. Although two subjects in the family had skin cancers, this dominant form of XP is not apparently associated with high risk, or large numbers of skin cancers in affected persons. (author)

Structure of the Unbound Form of HIV-1 Subtype A Protease: Comparison with Unbound Forms of Proteases from other HIV Subtypes

Energy Technology Data Exchange (ETDEWEB)

Robbins, Arthur H.; Coman, Roxana M.; Bracho-Sanchez, Edith; Fernandez, Marty A.; Gilliland, C.Taylor; Li, Mi; Agbandje-McKenna, Mavis; Wlodawer, Alexander; Dunn, Ben M.; McKenna, Robert (NCI); (Florida)

2010-03-12

The crystal structure of the unbound form of HIV-1 subtype A protease (PR) has been determined to 1.7 {angstrom} resolution and refined as a homodimer in the hexagonal space group P6{sub 1} to an R{sub cryst} of 20.5%. The structure is similar in overall shape and fold to the previously determined subtype B, C and F PRs. The major differences lie in the conformation of the flap region. The flaps in the crystal structures of the unbound subtype B and C PRs, which were crystallized in tetragonal space groups, are either semi-open or wide open. In the present structure of subtype A PR the flaps are found in the closed position, a conformation that would be more anticipated in the structure of HIV protease complexed with an inhibitor. The amino-acid differences between the subtypes and their respective crystal space groups are discussed in terms of the differences in the flap conformations.

Human orexin/hypocretin receptors form constitutive homo- and heteromeric complexes with each other and with human CB{sub 1} cannabinoid receptors

Energy Technology Data Exchange (ETDEWEB)

Jäntti, Maria H., E-mail: maria.jantti@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland); Mandrika, Ilona, E-mail: ilona@biomed.lu.lv [Latvian Biomedical Research and Study Centre, Ratsupites Str. 1, Riga LV 1067 (Latvia); Kukkonen, Jyrki P., E-mail: jyrki.kukkonen@helsinki.fi [Department of Veterinary Biosciences, POB 66, FIN-00014 University of Helsinki (Finland)

2014-03-07

Highlights: • OX{sub 1} and OX{sub 2} orexin and CB{sub 1} cannabinoid receptor dimerization was investigated. • Bioluminescence resonance energy transfer method was used. • All receptors readily formed constitutive homo- and heteromeric complexes. - Abstract: Human OX{sub 1} orexin receptors have been shown to homodimerize and they have also been suggested to heterodimerize with CB{sub 1} cannabinoid receptors. The latter has been suggested to be important for orexin receptor responses and trafficking. In this study, we wanted to assess the ability of the other combinations of receptors to also form similar complexes. Vectors for expression of human OX{sub 1}, OX{sub 2} and CB{sub 1} receptors, C-terminally fused with either Renilla luciferase or GFP{sup 2} green fluorescent protein variant, were generated. The constructs were transiently expressed in Chinese hamster ovary cells, and constitutive dimerization between the receptors was assessed by bioluminescence energy transfer (BRET). Orexin receptor subtypes readily formed homo- and hetero(di)mers, as suggested by significant BRET signals. CB{sub 1} receptors formed homodimers, and they also heterodimerized with both orexin receptors. Interestingly, BRET efficiency was higher for homodimers than for almost all heterodimers. This is likely to be due to the geometry of the interaction; the putatively symmetric dimers may place the C-termini in a more suitable orientation in homomers. Fusion of luciferase to an orexin receptor and GFP{sup 2} to CB{sub 1} produced more effective BRET than the opposite fusions, also suggesting differences in geometry. Similar was seen for the OX{sub 1}–OX{sub 2} interaction. In conclusion, orexin receptors have a significant propensity to make homo- and heterodi-/oligomeric complexes. However, it is unclear whether this affects their signaling. As orexin receptors efficiently signal via endocannabinoid production to CB{sub 1} receptors, dimerization could be an effective way

Sensitivity and variability of Presage dosimeter formulations in sheet form with application to SBRT and SRS QA

Energy Technology Data Exchange (ETDEWEB)

Dumas, Michael, E-mail: mdumas1127@gmail.com [Department of Radiation Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute Detroit, Detroit, Michigan 48201 and Department of Radiation Oncology, Henry Ford Hospital, Detroit, Michigan 48202 (United States); Rakowski, Joseph T. [Department of Radiation Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute Detroit, Detroit, Michigan 48201 (United States)

2015-12-15

Purpose: To measure sensitivity and stability of the Presage dosimeter in sheet form for various chemical concentrations over a range of clinical photon energies and examine its use for stereotactic body radiation therapy (SBRT) and stereotactic radiosurgery (SRS) QA. Methods: Presage polymer dosimeters were formulated to investigate and optimize their sensitivity and stability. The dosimeter is composed of clear polyurethane base, leucomalachite green (LMG) reporting dye, and bromoform radical initiator in 0.9–1.0 mm thick sheets. The chemicals are mixed together for 2 min, cast in an aluminum mold, and left to cure at 60 psi for a minimum of two days. Dosimeter response was characterized at energies Co-60, 6 MV, 10 MV flattening-filter free, 15 MV, 50 kVp (mean 19.2 keV), and Ir-192. The dosimeters were scanned by a Microtek Scanmaker i800 at 300 dpi, 2{sup 16} bit depth per color channel. Red component images were analyzed with ImageJ and RIT. SBRT QA was done with gamma analysis tolerances of 2% and 2 mm DTA. Results: The sensitivity of the Presage dosimeter increased with increasing concentration of bromoform. Addition of tin catalyst decreased curing time and had negligible effect on sensitivity. LMG concentration should be at least as high as the bromoform, with ideal concentration being 2% wt. Gamma Knife SRS QA measurements of relative output and profile widths were within 2% of manufacturer’s values validated at commissioning, except the 4 mm collimator relative output which was within 3%. The gamma pass rate of Presage with SBRT was 73.7%, compared to 93.1% for EBT2 Gafchromic film. Conclusions: The Presage dosimeter in sheet form was capable of detecting radiation over all tested photon energies and chemical concentrations. The best sensitivity and photostability of the dosimeter were achieved with 2.5% wt. LMG and 8.2% wt. bromoform. Scanner used should not emit any UV radiation as it will expose the dosimeter, as with the Epson 10000 XL scanner

In silico analysis of the three-dimensional structures of the homodimer of uridine phosphorylase from Yersinia Pseudotuberculosis in the ligand-free state and in a complex with 5-fluorouracil

Energy Technology Data Exchange (ETDEWEB)

Lashkov, A. A., E-mail: alashkov83@gmail.com; Sotnichenko, S. E.; Mikhailov, A. M. [Russian Academy of Sciences, Shubnikov Institute of Crystallography (Russian Federation)

2013-03-15

Pseudotuberculosis is an acute infectious disease characterized by a lesion of the gastrointestinal tract. A positive therapeutic effect can be achieved by selectively suppressing the activity of uridine phosphorylase from the causative agent of the disease Yersinia pseudotuberculosis. The synergistic effect of a combination of the chemotherapeutic agent 5-fluorouracil and antimicrobial drugs, which block the synthesis of pyrimidine bases, on the cells of pathogenic protozoa and bacteria is described in the literature. The three-dimensional structures of uridine phosphorylase from Yersinia pseudotuberculosis (YptUPh) both in the ligand-free state and in complexes with pharmacological agents are unknown, which hinders the search for and design of selective inhibitors of YptUPh. The three-dimensional structure of the ligand-free homodimer of YptUPh was determined by homology-based molecular modeling. The three-dimensional structure of the subunit of the YptUPh molecule belongs to {alpha}/{beta} proteins, and its topology is a three-layer {alpha}/{beta}/{alpha} sandwich. The subunit monomer of the YptUPh molecule consists of 38% helices and 24% {beta} strands. A model of the homodimer structure of YptUPh in a complex with 5-FU was obtained by the molecular docking. The position of 5-FU in the active site of the molecule is very consistent with the known data on the X-ray diffraction structures of other bacterial uridine phosphorylases (the complex of uridine phosphorylase from Salmonella typhimurium (StUPh) with 5-FU, ID PDB: 4E1V and the complex of uridine phosphorylase from Escherichia coli (EcUPh) with 5-FU and ribose 1-phosphate, ID PDB: 1RXC).

Friendship Conflict, Conflict Responses, and Instability: Unique Links to Anxious and Angry Forms of Rejection Sensitivity

Science.gov (United States)

Croft, Carissa D.; Zimmer-Gembeck, Melanie J.

2014-01-01

Rejection sensitivity (RS) instigates conflict and prompts maladaptive conflict responses within romantic relationships. We tested whether RS had similar effects within friendships (N = 262, X[subscript age] = 11.7) by investigating whether (a) RS was associated with more frequent conflict, (b) two RS forms prompted different conflict responses,…

On the sensitivity of nucleon-nucleon correlations to the form of short-range potential

International Nuclear Information System (INIS)

Gmitro, M.; Kvasil, J.; Lednicky, R.; Lyuboshitz, V.L.

1986-01-01

Nucleon-nucleon correlation characteristics are calculated for several phenomenological and realistic strong potentials. The results show that a square-well potential reasonably well approximates the nucleon-nucleon interaction if one calculates the correlations between nucleons generated in a region with an r.m.s. radius larger than 1.5-2 fm. Vice versa, the correlations of nucleons emitted from a smaller generation region are sensitive to the form of the assumed nucleon-nucleon potential. (author)

Facile Conversion Synthesis of Densely-Formed Branched ZnO-Nanowire Arrays for Quantum-Dot-Sensitized Solar Cells

International Nuclear Information System (INIS)

Lee, Woojin; Kang, Suji; Hwang, Taehyun; Kim, Kunsu; Woo, Hyungsub; Lee, Byungho; Kim, Jaewon; Kim, Jinhyun; Park, Byungwoo

2015-01-01

Highlights: •3-D hierarchically branched ZnO nanowires by a facile synthesis with seed nucleation. •Nanobranching enhances the efficiency by a factor of two compared with the bare QDSC. •Attributed to the increased sensitizer by ∼80% and decreased transmittance by ∼17%. •Optimized nanostructures correlate with the light-harvesting and carrier-collection efficiencies. -- Abstract: An effective way of synthesizing densely-formed branched ZnO-nanowire arrays was developed by a straightforward conversion reaction of ZnS into ZnO. Hierarchically structured ZnO nanowires are utilized for quantum-dot-sensitized solar cells (QDSCs), having resulted in the conversion-efficiency enhancement by a factor of two compared to the bare ZnO nanowires. This is attributed to the increased CdS-quantum-dot sensitizer by ∼80% and decreased diffused transmittance by ∼17%, induced by the densely-formed branched nanowires. The correlations between the branched nanostructures and photovoltaic performances are systematically investigated in terms of light absorption, charge-transfer resistance, and carrier lifetime. This facile and controllable branched nanowire synthesis is anticipated to be applicable to other semiconductor photoanodes for efficient light harvesting and charge collecting properties

Cardiac Calcium ATPase Dimerization Measured by Cross-Linking and Fluorescence Energy Transfer.

Science.gov (United States)

Blackwell, Daniel J; Zak, Taylor J; Robia, Seth L

2016-09-20

The cardiac sarco/endoplasmic reticulum calcium ATPase (SERCA) establishes the intracellular calcium gradient across the sarcoplasmic reticulum membrane. It has been proposed that SERCA forms homooligomers that increase the catalytic rate of calcium transport. We investigated SERCA dimerization in rabbit left ventricular myocytes using a photoactivatable cross-linker. Western blotting of cross-linked SERCA revealed higher-molecular-weight species consistent with SERCA oligomerization. Fluorescence resonance energy transfer measurements in cells transiently transfected with fluorescently labeled SERCA2a revealed that SERCA readily forms homodimers. These dimers formed in the absence or presence of the SERCA regulatory partner, phospholamban (PLB) and were unaltered by PLB phosphorylation or changes in calcium or ATP. Fluorescence lifetime data are compatible with a model in which PLB interacts with a SERCA homodimer in a stoichiometry of 1:2. Together, these results suggest that SERCA forms constitutive homodimers in live cells and that dimer formation is not modulated by SERCA conformational poise, PLB binding, or PLB phosphorylation. Copyright © 2016 Biophysical Society. Published by Elsevier Inc. All rights reserved.

The Escherichia coli BolA Protein IbaG Forms a Histidine-Ligated [2Fe-2S]-Bridged Complex with Grx4.

Science.gov (United States)

Dlouhy, Adrienne C; Li, Haoran; Albetel, Angela-Nadia; Zhang, Bo; Mapolelo, Daphne T; Randeniya, Sajini; Holland, Ashley A; Johnson, Michael K; Outten, Caryn E

2016-12-13

Two ubiquitous protein families have emerged as key players in iron metabolism, the CGFS-type monothiol glutaredoxins (Grxs) and the BolA proteins. Monothiol Grxs and BolA proteins form heterocomplexes that have been implicated in Fe-S cluster assembly and trafficking. The Escherichia coli genome encodes members of both of these proteins families, namely, the monothiol glutaredoxin Grx4 and two BolA family proteins, BolA and IbaG. Previous work has demonstrated that E. coli Grx4 and BolA interact as both apo and [2Fe-2S]-bridged heterodimers that are spectroscopically distinct from [2Fe-2S]-bridged Grx4 homodimers. However, the physical and functional interactions between Grx4 and IbaG are uncharacterized. Here we show that co-expression of Grx4 with IbaG yields a [2Fe-2S]-bridged Grx4-IbaG heterodimer. In vitro interaction studies indicate that IbaG binds the [2Fe-2S] Grx4 homodimer to form apo Grx4-IbaG heterodimer as well as the [2Fe-2S] Grx4-IbaG heterodimer, altering the cluster stability and coordination environment. Additionally, spectroscopic and mutagenesis studies provide evidence that IbaG ligates the Fe-S cluster via the conserved histidine that is present in all BolA proteins and by a second conserved histidine that is present in the H/C loop of two of the four classes of BolA proteins. These results suggest that IbaG may function in Fe-S cluster assembly and trafficking in E. coli as demonstrated for other BolA homologues that interact with monothiol Grxs.

Ionizing radiation method for forming acrylic pressure sensitive adhesives and coated substrates

International Nuclear Information System (INIS)

Dowbenko, R.; Christenson, R.M.

1975-01-01

Pressure-sensitive adhesive having improved adhesive properties are formed by subjecting a mixture comprising a monomer selected from the group consisting of alkyl acrylates, hydroxyalkyl acrylates, alkoxyalkyl acrylates, cyanoalkyl acrylates, alkyl methacrylates, hydroxyalkyl methacrylates, alkoxyalkyl methacrylates, cyanoalkyl methacrylates, N-alkoxymethylacrylamides, and N-alkoxymethylmethacrylamides, and a homopolymer or copolymer selected from the group consisting of polymers of alkyl acrylates, hydroxyalkyl acrylates, alkoxyalkyl acrylates, cyanoalkyl acrylates, alkyl methacrylates, hydroxyalkyl methacrylates, alkoxyalkyl methacrylates, cyanoalkyl methacrylates, acrylamide, methacrylamide, N-(substituted alkyl) acrylamides, N-(substituted alkyl) methacrylamides, alkyl acrylamides, alkyl methacrylamides, and N-alkoxymethylacrylamides and N-alkoxymethylmethacrylamides to ionizing irradiation. The adhesive material finds utility as binding resins in laminates, coatings on substrates, and as film adhesives. (U.S.)

Albumin Homodimers in Patients with Cirrhosis: Clinical and Prognostic Relevance of a Novel Identified Structural Alteration of the Molecule.

Science.gov (United States)

Baldassarre, Maurizio; Domenicali, Marco; Naldi, Marina; Laggetta, Maristella; Giannone, Ferdinando A; Biselli, Maurizio; Patrono, Daniela; Bertucci, Carlo; Bernardi, Mauro; Caraceni, Paolo

2016-10-26

Decompensated cirrhosis is associated to extensive post-transcriptional changes of human albumin (HA). This study aims to characterize the occurrence of HA homodimerization in a large cohort of patients with decompensated cirrhosis and to evaluate its association with clinical features and prognosis. HA monomeric and dimeric isoforms were identified in peripheral blood by using a HPLC-ESI-MS technique in 123 cirrhotic patients hospitalized for acute decompensation and 50 age- and sex-comparable healthy controls. Clinical and biochemical parameters were recorded and patients followed up to one year. Among the monomeric isoforms identified, the N- and C-terminal truncated and the native HA underwent homodimerization. All three homodimers were significantly more abundant in patients with cirrhosis, acute-on-chronic liver failure and correlate with the prognostic scores. The homodimeric N-terminal truncated isoform was independently associated to disease complications and was able to stratify 1-year survival. As a result of all these changes, the monomeric native HA was significantly decreased in patients with cirrhosis, being also associated with a poorer prognosis. In conclusion homodimerization is a novel described structural alteration of the HA molecule in decompensated cirrhosis and contributes to the progressive reduction of the monomeric native HA, the only isoform provided of structural and functional integrity.

Central nociceptive sensitization vs. spinal cord training: Opposing forms of plasticity that dictate function after complete spinal cord injury

Directory of Open Access Journals (Sweden)

Adam R Ferguson

2012-10-01

Full Text Available The spinal cord demonstrates several forms of plasticity that resemble brain-dependent learning and memory. Among the most studied form of spinal plasticity is spinal memory for noxious (nociceptive stimulation. Numerous papers have described central pain as a spinally-stored memory that enhances future responses to cutaneous stimulation. This phenomenon, known as central sensitization, has broad relevance to a range of pathological conditions. Work from the spinal cord injury (SCI field indicates that the lumbar spinal cord demonstrates several other forms of plasticity, including formal learning and memory. After complete thoracic SCI, the lumbar spinal cord can be trained by delivering stimulation to the hindleg when the leg is extended. In the presence of this response-contingent stimulation the spinal cord rapidly learns to hold the leg in a flexed position, a centrally mediated effect that meets the formal criteria for instrumental (response-outcome learning. Instrumental flexion training produces a central change in spinal plasticity that enables future spinal learning on both the ipsilateral and contralateral leg. However, if stimulation is given in a response-independent manner, the spinal cord develops central maladaptive plasticity that undermines future spinal learning on both legs. The present paper tests for interactions between spinal cord training and central nociceptive sensitization after complete spinal cord transection. We found that spinal training alters future central sensitization by intradermal formalin (24 h post-training. Conversely intradermal formalin impaired future spinal learning (24 h post-injection. Because the NMDA receptor has been implicated in formalin-induced central sensitization, we tested whether pretreatment with NMDA affects spinal learning. We found intrathecal NMDA impaired learning in a dose-dependent fashion, and that this effect endures for at least 24h. These data provide strong evidence for an

Comparison of central HER2 testing with quantitative total HER2 expression and HER2 homodimer measurements using a novel proximity-based assay.

Science.gov (United States)

Huang, Weidong; Reinholz, Monica; Weidler, Jodi; Yolanda, Lie; Paquet, Agnes; Whitcomb, Jeannette; Lingle, Wilma; Jenkins, Robert B; Chen, Beiyun; Larson, Jeffrey S; Tan, Yuping; Sherwood, Thomas; Bates, Michael; Perez, Edith A

2010-08-01

The accuracy and reliability of immunohistochemical analysis and in situ hybridization for the assessment of HER2 status remains a subject of debate. We developed a novel assay (HERmark Breast Cancer Assay, Monogram Biosciences, South San Francisco, CA) that provides precise quantification of total HER2 protein expression (H2T) and HER2 homodimers (H2D) in formalin-fixed, paraffin-embedded tissue specimens. H2T and H2D results of 237 breast cancers were compared with those of immunohistochemical studies and fluorescence in situ hybridization (FISH) centrally performed at the Mayo Clinic, Rochester, MN. H2T described a continuum across a wide dynamic range ( approximately 2.5 log). Excluding the equivocal cases, HERmark showed 98% concordance with immunohistochemical studies for positive and negative assay values. For the 94 immunohistochemically equivocal cases, 67% and 39% concordance values were observed between HERmark and FISH for positive and negative assay values, respectively. Polysomy 17 in the absence of HER2 gene amplification did not result in HER2 overexpression as evaluated quantitatively using the HERmark assay.

Interaction of the phosphorylated DNA-binding domain in nuclear receptor CAR with its ligand-binding domain regulates CAR activation.

Science.gov (United States)

Shizu, Ryota; Min, Jungki; Sobhany, Mack; Pedersen, Lars C; Mutoh, Shingo; Negishi, Masahiko

2018-01-05

The nuclear protein constitutive active/androstane receptor (CAR or NR1I3) regulates several liver functions such as drug and energy metabolism and cell growth or death, which are often involved in the development of diseases such as diabetes and hepatocellular carcinoma. CAR undergoes a conversion from inactive homodimers to active heterodimers with retinoid X receptor α (RXRα), and phosphorylation of the DNA-binding domain (DBD) at Thr-38 in CAR regulates this conversion. Here, we uncovered the molecular mechanism by which this phosphorylation regulates the intramolecular interaction between CAR's DBD and ligand-binding domain (LBD), enabling the homodimer-heterodimer conversion. Phosphomimetic substitution of Thr-38 with Asp increased co-immunoprecipitation of the CAR DBD with CAR LBD in Huh-7 cells. Isothermal titration calorimetry assays also revealed that recombinant CAR DBD-T38D, but not nonphosphorylated CAR DBD, bound the CAR LBD peptide. This DBD-LBD interaction masked CAR's dimer interface, preventing CAR homodimer formation. Of note, EGF signaling weakened the interaction of CAR DBD T38D with CAR LBD, converting CAR to the homodimer form. The DBD-T38D-LBD interaction also prevented CAR from forming a heterodimer with RXRα. However, this interaction opened up a CAR surface, allowing interaction with protein phosphatase 2A. Thr-38 dephosphorylation then dissociated the DBD-LBD interaction, allowing CAR heterodimer formation with RXRα. We conclude that the intramolecular interaction of phosphorylated DBD with the LBD enables CAR to adapt a transient monomer configuration that can be converted to either the inactive homodimer or the active heterodimer.

Elucidation of the Specific Formation of Homo- and Heterodimeric Forms of ThbZIP1 and Its Role in Stress

Directory of Open Access Journals (Sweden)

Xianguang Nie

2014-06-01

Full Text Available Protein–protein interactions are important for the molecular understanding of the biological processes of proteins. The dimerization of bZIPs (basic leucine zipper proteins is involved in modifying binding site specificities, altering dimer stability, and permitting a new set of specific protein-to-protein interactions to occur at the promoter. In the present study, we studied the whether ThbZIP1 form homo- and heterodimers using the yeast two-hybrid method. Five bZIP genes were cloned from Tamarix hispida to investigate their interaction with ThbZIP1. Our results showed that ThbZIP1 can form homodimers with itself, and three out of five bZIPs could interact with the ThbZIP1 protein to form heterodimers. Real-time RT-PCR results suggested that these ThbZIPs can all respond to abiotic stresses and abscisic acid (ABA, and shared very similar expression patterns in response to NaCl, ABA or PEG6000. Subcellular localization studies showed that all ThbZIPs are targeted to the nucleus. Our results showed that ThbZIP1 are dimeric proteins, which can form homo- or heterodimers.

Process for the production of a pressure-sensitive carbonless copy sheet using microcapsules formed in situ in a radiation curable binder

International Nuclear Information System (INIS)

Lee, Y.S.; Shackle, D.R.

1978-01-01

A process is provided for the production of a coating composition containing microcapsules having a hydrophilic core for use in the manufacture of pressure-sensitive carbonless transfer papers comprising the following steps. A hydrophilic emulsion component is prepared by dispersing at least one chromogenic material being soluble in the hydrophilic liquid. A hydrophobic emulsion component is prepared by dispersing an emulsifier in a radiation curable hydrophobic liquid. A first wall-forming material and a second wall-forming material are added to the hydrophobic emulsion component, with mixing. The first and second wall-forming materials are soluble in the hydrophobic emulsion component, and the first wall-forming material is reactive with the second wall-forming material to form a polymeric capsule wall. The resultant polymeric capsule wall is substantially insoluble in the hydrophilic and the hydrophobic emulsion components. The hydrophobic emulsion component is mixed together with the hydrophilic emulsion component to form an emulsion containing droplets of the hydrophilic emulsion component dispersed in the hydrophobic emulsion component. Mixing is maintained for a period of time sufficient to allow the first and second wall-forming materials to react to form a dispersion of microcapsules in the hydrophobic emulsion component. The formed microcapsules have capsule walls substantially impermeable to the hydrophobic and the hydrophilic emulsion components. Pressure-sensitive carbonless transfer paper may be produced by applying the despersion of the microcapsules prepared as above to a substrate,and curing the dispersion by subjecting the dispersion on the substrate to radiation for a period of time sufficient to cure the radiation curable hydrophobic liquid, thereby producing a tack-free, resinous film on the substrate

An investigation of the sensitivity of a land surface model to climate change using a reduced form model

Energy Technology Data Exchange (ETDEWEB)

Lynch, A.H.; McIlwaine, S. [PAOS/CIRES, Univ. of Colorado, Boulder, CO (United States); Beringer, J. [Inst. of Arctic Biology, Univ. of Alaska, Fairbanks (United States); Bonan, G.B. [National Center for Atmospheric Research, Boulder, CO (United States)

2001-05-01

In an illustration of a model evaluation methodology, a multivariate reduced form model is developed to evaluate the sensitivity of a land surface model to changes in atmospheric forcing. The reduced form model is constructed in terms of a set of ten integrative response metrics, including the timing of spring snow melt, sensible and latent heat fluxes in summer, and soil temperature. The responses are evaluated as a function of a selected set of six atmospheric forcing perturbations which are varied simultaneously, and hence each may be thought of as a six-dimensional response surface. The sensitivities of the land surface model are interdependent and in some cases illustrate a physically plausible feedback process. The important predictors of land surface response in a changing climate are the atmospheric temperature and downwelling longwave radiation. Scenarios characterized by warming and drying produce a large relative response compared to warm, moist scenarios. The insensitivity of the model to increases in precipitation and atmospheric humidity is expected to change in applications to coupled models, since these parameters are also strongly implicated, through the representation of clouds, in the simulation of both longwave and shortwave radiation. (orig.)

A theoretical and spectroscopic study of co-amorphous naproxen and indomethacin

DEFF Research Database (Denmark)

Löbmann, Korbinian; Laitinen, Riikka; Grohganz, Holger

2013-01-01

. In this study, the co-amorphous drug mixture containing naproxen (NAP) and indomethacin (IND) was investigated using infrared spectroscopy (IR) and quantum mechanical calculations. The structures of both drugs were optimized as monomer, homodimer and heterodimer using density functional theory and used...... for the calculation of IR spectra. Conformational analysis confirmed that the optimized structures were suitable for the theoretical prediction of the spectra. Vibrational modes from the calculation could be matched with experimentally observed spectra for crystalline and amorphous NAP and IND, and it could be shown...... that both drugs exist as homodimers in their respective individual amorphous form. With the results from the experimental single amorphous drugs and theoretical homodimers, a detailed analysis of the experimental co-amorphous and theoretical heterodimer spectra was performed and evaluated. It is suggested...

Dimerization of nitrophorin 4 at low pH and comparison to the K1A mutant of nitrophorin 1.

Science.gov (United States)

Berry, Robert E; Yang, Fei; Shokhireva, Tatiana K; Amoia, Angela M; Garrett, Sarah A; Goren, Allena M; Korte, Stephanie R; Zhang, Hongjun; Weichsel, Andrzej; Montfort, William R; Walker, F Ann

2015-01-20

Nitrophorin 4, one of the four NO-carrying heme proteins from the salivary glands of Rhodnius prolixus, forms a homodimer at pH 5.0 with a Kd of ∼8 μM. This dimer begins to dissociate at pH 5.5 and is completely dissociated to monomer at pH 7.3, even at 3.7 mM. The dimer is significantly stabilized by binding NO to the heme and at pH 7.3 would require dilution to well below 0.2 mM to completely dissociate the NP4-NO homodimer. The primary techniques used for investigating the homodimer and the monomer-dimer equilibrium were size-exclusion fast protein liquid chromatography at pH 5.0 and (1)H{(15)N} heteronuclear single-quantum coherence spectroscopy as a function of pH and concentration. Preparation of site-directed mutants of NP4 (A1K, D30A, D30N, V36A/D129A/L130A, K38A, R39A, K125A, K125E, D132A, L133V, and K38Q/R39Q/K125Q) showed that the N-terminus, D30, D129, D132, at least one heme propionate, and, by association, likely also E32 and D35 are involved in the dimerization. The "closed loop" form of the A-B and G-H flexible loops of monomeric NP4, which predominates in crystal structures of the monomeric protein reported at pH 5.6 but not at pH 7.5 and which involves all of the residues listed above except D132, is required for dimer formation. Wild-type NP1 does not form a homodimer, but NP1(K1A) and native N-terminal NP1 form dimers in the presence of NO. The homodimer of NP1, however, is considerably less stable than that of NP4 in the absence of NO. This suggests that additional aspartate or glutamate residues present in the C-terminal region of NP4, but not NP1, are also involved in stabilizing the dimer.

Exon-skipping strategy by ratio modulation between cytoprotective versus pro-apoptotic clusterin forms increased sensitivity of LNCaP to cell death.

Directory of Open Access Journals (Sweden)

Abdellatif Essabbani

Full Text Available BACKGROUND: In prostate cancer the secreted form of clusterin (sCLU has been described as an anti-apoptotic protein whose expression is increased after therapeutic intervention, whereas, the nuclear protein form nCLU was reported to have pro-apoptotic properties. METHODOLOGY: In order to provide new therapeutic approaches targeting CLU, we developed a strategy based on exon skipping by using a lentiviral construct to preferentially induce the nuclear spliced form of the protein. The molecular construct was transduced in LNCaP cells for testing the modulation of sensitivity of the transduced cells to pro-apoptotic stress. RESULTS AND CONCLUSIONS: We showed an increase of nCLU/sCLU expression ratio in the prostate cancer cell line "LNCaP" after lentiviral vector-U7 nCLU transduction. Moreover, we showed a significant inhibition of cell proliferation in nCLU-U7 LNCaP cells after treatment with cisplatin and after exposure to ionizing radiation compared to control cells. Finally, we showed that nCLU-U7 LNCaP cells exposure to UV-C significantly reduced an increase of cell death compared to control. Finally, we showed that modulating nCLU expression had profound impact on Ku70/Bax interaction as well as Rad17 expression which could be a key mechanism in sensitizing cells to cell death. In conclusion, this is the first report showing that increasing of nCLU/sCLU expression ratio by using an "on demand alternative splicing" strategy successfully increased sensitivity to radiotherapy and chemotherapy of prostate cancer cells.

Identification of the Dimer Exchange Interface of the Bacterial DNA Damage Response Protein UmuD.

Science.gov (United States)

Murison, David A; Timson, Rebecca C; Koleva, Bilyana N; Ordazzo, Michael; Beuning, Penny J

2017-09-12

The Escherichia coli SOS response, an induced DNA damage response pathway, confers survival on bacterial cells by providing accurate repair mechanisms as well as the potentially mutagenic pathway translesion synthesis (TLS). The umuD gene products are upregulated after DNA damage and play roles in both nonmutagenic and mutagenic aspects of the SOS response. Full-length UmuD is expressed as a homodimer of 139-amino-acid subunits, which eventually cleaves its N-terminal 24 amino acids to form UmuD'. The cleavage product UmuD' and UmuC form the Y-family polymerase DNA Pol V (UmuD' 2 C) capable of performing TLS. UmuD and UmuD' exist as homodimers, but their subunits can readily exchange to form UmuDD' heterodimers preferentially. Heterodimer formation is an essential step in the degradation pathway of UmuD'. The recognition sequence for ClpXP protease is located within the first 24 amino acids of full-length UmuD, and the partner of full-length UmuD, whether UmuD or UmuD', is degraded by ClpXP. To better understand the mechanism by which UmuD subunits exchange, we measured the kinetics of exchange of a number of fluorescently labeled single-cysteine UmuD variants as detected by Förster resonance energy transfer. Labeling sites near the dimer interface correlate with increased rates of exchange, indicating that weakening the dimer interface facilitates exchange, whereas labeling sites on the exterior decrease the rate of exchange. In most but not all cases, homodimer and heterodimer exchange exhibit similar rates, indicating that somewhat different molecular surfaces mediate homodimer exchange and heterodimer formation.

Withanolide D Exhibits Similar Cytostatic Effect in Drug-Resistant and Drug-Sensitive Multiple Myeloma Cells

Directory of Open Access Journals (Sweden)

Mark E. Issa

2017-09-01

Full Text Available In spite of recent therapeutic advances, multiple myeloma (MM remains a malignancy with very low curability. This has been partly attributed to the existence of a drug-resistant subpopulation known as cancer stem cells (CSCs. MM-CSCs are equipped with the necessary tools that render them highly resistant to virtually all conventional therapies. In this study, the growth inhibitory effects of withanolide D (WND, a steroidal lactone isolated from Withania somnifera, on drug-sensitive tumoral plasma cells and drug-resistant MM cells have been investigated. In MTT/XTT assays, WND exhibited similar cytostatic effects between drug-resistant and drug-sensitive cell lines in the nM range. WND also induced cell death and apoptosis in MM-CSCs and RPMI 8226 cells, as examined by the calcein/ethidium homodimer and annexin V/propidium iodide stainings, respectively. To determine whether P-glycoprotein (P-gp efflux affected the cytostatic activity of WND, P-gp was inhibited with verapamil and results indicated that the WND cytostatic effect in MM-CSCs was independent of P-gp efflux. Furthermore, WND did not increase the accumulation of the fluorescent P-gp substrate rhodamine 123 in MM-CSCs, suggesting that WND may not inhibit P-gp at the tested relevant doses. Therefore, the WND-induced cytostatic effect may be independent of P-gp efflux. These findings warrant further investigation of WND in MM-CSC animal models.

Mice expressing a "hyper-sensitive" form of the CB1 cannabinoid receptor (CB1 show modestly enhanced alcohol preference and consumption.

Directory of Open Access Journals (Sweden)

David J Marcus

Full Text Available We recently characterized S426A/S430A mutant mice expressing a desensitization-resistant form of the CB1 receptor. These mice display an enhanced response to endocannabinoids and ∆9-THC. In this study, S426A/S430A mutants were used as a novel model to test whether ethanol consumption, morphine dependence, and reward for these drugs are potentiated in mice with a "hyper-sensitive" form of CB1. Using an unlimited-access, two-bottle choice, voluntary drinking paradigm, S426A/S430A mutants exhibit modestly increased intake and preference for low (6% but not higher concentrations of ethanol. S426A/S430A mutants and wild-type mice show similar taste preference for sucrose and quinine, exhibit normal sensitivity to the hypothermic and ataxic effects of ethanol, and have normal blood ethanol concentrations following administration of ethanol. S426A/S430A mutants develop robust conditioned place preference for ethanol (2 g/kg, morphine (10 mg/kg, and cocaine (10 mg/kg, demonstrating that drug reward is not changed in S426A/S430A mutants. Precipitated morphine withdrawal is also unchanged in opioid-dependent S426A/S430A mutant mice. Although ethanol consumption is modestly changed by enhanced CB1 signaling, reward, tolerance, and acute sensitivity to ethanol and morphine are normal in this model.

Short Form of Weinstein Noise Sensitivity Scale (NSS-SF): Reliability, Validity and Gender Invariance among Chinese Individuals.

Science.gov (United States)

Zhong, Tao; Chung, Pak-Kwong; Liu, Jing Dong

2018-02-01

Independent from noise exposure, noise sensitivity plays a pivotal role in people's noise annoyance perception and concomitant health deteriorations. The present study empirically investigated the psychometric properties of the Chinese version of the Weinstein Noise Sensitivity Scale-Short Form (CNSS-SF), the widely used inventory measuring individual differences in noise perception. In total, 373 Chinese participants (age = 21.41 ± 3.36) completed the online, anonymous questionnaire package. Examination of the CNSS-SF's reliability (internal consistency), factorial validity through validation and cross-validation, nomological validity and measurement invariance across gender groups were undertaken. The Cronbach alpha coefficients and composite reliabilities indicated sufficient reliability of the CNSS-SF. Two confirmatory factor analyses (CFA), in two randomly partitioned groups of participants, substantiated the factorial validity of the scale. The nomological validity of the scale was also corroborated by the significant positive association of its score with the trait anxiety score. Measurement invariance of the CNSS-SF was also found across genders via multi-group CFA. Though not without limitations, findings from the present research provide promising evidence for the utility of the scale in measuring noise sensitivity among the Chinese population. The availability of the CNSS-SF can promote research related to environmental noise and health in China, as well as facilitate cross-cultural comparisons. Copyright © 2018 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Migratory polyarthritis as an adverse effect of thiamazole use in a 13-year-old girl with Graves' disease

NARCIS (Netherlands)

Janson, J.A.; Laat, P. de; Draaisma, J.M.T.

2015-01-01

Graves' disease is the most prevalent cause of hyperthyroidism in children. The treatment commonly involves antithyroid therapy using a thionamide. We present a case of a 13-year-old girl with the antithyroid arthritis syndrome, presenting as a migratory polyarthritis, after the initiation of

Nodeless vibrational amplitudes and quantum nonadiabatic dynamics in the nested funnel for a pseudo Jahn-Teller molecule or homodimer

Science.gov (United States)

Peters, William K.; Tiwari, Vivek; Jonas, David M.

2017-11-01

The nonadiabatic states and dynamics are investigated for a linear vibronic coupling Hamiltonian with a static electronic splitting and weak off-diagonal Jahn-Teller coupling through a single vibration with a vibrational-electronic resonance. With a transformation of the electronic basis, this Hamiltonian is also applicable to the anti-correlated vibration in a symmetric homodimer with marginally strong constant off-diagonal coupling, where the non-adiabatic states and dynamics model electronic excitation energy transfer or self-exchange electron transfer. For parameters modeling a free-base naphthalocyanine, the nonadiabatic couplings are deeply quantum mechanical and depend on wavepacket width; scalar couplings are as important as the derivative couplings that are usually interpreted to depend on vibrational velocity in semiclassical curve crossing or surface hopping theories. A colored visualization scheme that fully characterizes the non-adiabatic states using the exact factorization is developed. The nonadiabatic states in this nested funnel have nodeless vibrational factors with strongly avoided zeroes in their vibrational probability densities. Vibronic dynamics are visualized through the vibrational coordinate dependent density of the time-dependent dipole moment in free induction decay. Vibrational motion is amplified by the nonadiabatic couplings, with asymmetric and anisotropic motions that depend upon the excitation polarization in the molecular frame and can be reversed by a change in polarization. This generates a vibrational quantum beat anisotropy in excess of 2/5. The amplitude of vibrational motion can be larger than that on the uncoupled potentials, and the electronic population transfer is maximized within one vibrational period. Most of these dynamics are missed by the adiabatic approximation, and some electronic and vibrational motions are completely suppressed by the Condon approximation of a coordinate-independent transition dipole between

Three molecular forms of atrial natriuretic peptides: quantitative analysis and biological characterization.

Science.gov (United States)

Nagai-Okatani, Chiaki; Kangawa, Kenji; Minamino, Naoto

2017-07-01

Atrial natriuretic peptide (ANP) is primarily produced in the heart tissue and plays a pivotal role in maintaining cardiovascular homeostasis in endocrine and autocrine/paracrine systems and has clinical applications as a biomarker and a therapeutic agent for cardiac diseases. ANP is synthesized by atrial cardiomyocytes as a preprohormone that is processed by a signal peptidase and stored in secretory granules as a prohormone. Subsequent proteolytic processing of ANP by corin during the secretion process results in a bioactive form consisting of 28 amino acid residues. Mechanical stretch of the atrial wall and multiple humoral factors directly stimulates the transcription and secretion of ANP. Secreted ANP elicits natriuretic and diuretic effects via cyclic guanosine monophosphate produced through binding to the guanylyl cyclase-A/natriuretic peptide receptor-A. Circulating ANP is subjected to rapid clearance by a natriuretic peptide receptor-C-mediated mechanism and proteolytic degradation by neutral endopeptidase. In humans, ANP is present as three endogenous molecular forms: bioactive α-ANP, a homodimer of α-ANP designated as β-ANP, and an ANP precursor designated as proANP (also referred to as γ-ANP). The proANP and especially β-ANP, as minor forms in circulation, are notably increased in patients with cardiac diseases, suggesting the utility of monitoring the pathophysiological conditions that result in abnormal proANP processing that cannot be monitored by inactive N-terminal proANP-related fragments. Emerging plate-based sandwich immunoassays for individual quantitation of the three ANP forms enables evaluation of diagnostic implications and net ANP bioactivity. This new tool may provide further understanding in the pathophysiology of cardiac diseases. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

New insights into the molecular mechanism of E-cadherin-mediated cell adhesion by free energy calculations

DEFF Research Database (Denmark)

Doro, Fabio; Saladino, Giorgio; Belvisi, Laura

2015-01-01

Three-dimensional domain swapping is an important mode of protein association leading to the formation of stable dimers. Monomers associating via this mechanism mutually exchange a domain to form a homodimer. Classical cadherins, an increasingly important target for anticancer therapy, use domain...... swapping to mediate cell adhesion. However, despite its importance, the molecular mechanism of domain swapping is still debated. Here, we study the conformational changes that lead to activation and dimerization via domain swapping of E-cadherin. Using state-of-the-art enhanced sampling atomistic......" mechanism in which monomers in an active conformational state bind to form a homodimer, analogous to the conformational selection mechanism often observed in ligand-target binding. Moreover, we find that the open state population is increased in the presence of calcium ions at the extracellular boundary...

A report of three cases of jaundice with thyrotoxicosis | Akande ...

African Journals Online (AJOL)

Background: Jaundice and hepatic dysfunction have been reported in patients with thyrotoxicosis and could be due to different mechanisms. Objective: To describe three cases of jaundice occurring in patients with thyrotoxicosis and to illustrate the importance of early institution of thionamides when indicated. Methods: We ...

Behavioral sensitization after repeated formaldehyde exposure in rats.

Science.gov (United States)

Sorg, B A; Hochstatter, T

1999-01-01

Multiple chemical sensitivity (MCS) is a phenomenon whereby individuals report increased sensitivity to chemicals in the environment, and attribute their sensitivities to prior exposure to the same or often structurally unrelated chemicals. A leading hypothesis suggests that MCS is akin to behavioral sensitization observed in rodents after repeated exposure to drugs of abuse or environmental stressors. Sensitization occurring within limbic circuitry of the central nervous system (CNS) may explain the multisymptom complaints in individuals with MCS. The present studies represent the continuing development of an animal model for MCS, the basis of which is the CNS sensitization hypothesis. Three behaviors were assessed in rats repeatedly exposed to formaldehyde (Form) inhalation. In the first series of experiments, rats were given high-dose Form exposure (11 parts per million [ppm]; 1 h/day x 7 days) or low-dose Form exposure (1 ppm; either 1 h/day x 7 days or 1 h/day x 5 days/week x 4 weeks). Within a few days after discontinuing daily Form, cocaine-induced locomotor activity was elevated after high-dose Form or 20 days of low-dose Form inhalation. Approximately 1 month later, cocaine-induced locomotor activity remained significantly elevated in the 20-day Form-exposed rats. The second experiment assessed whether prior exposure to Form (20 days, as above) would alter the ability to condition to an odor (orange oil) paired with footshock. The results suggested a tendency to increase the conditioned fear response to the odor but not the context of the footshock box, and a decreased tendency to extinguish the conditioned fear response to odor. The third experiment examined whether CNS sensitization to daily cocaine or stress would alter subsequent avoidance responding to odor (Form). Daily cocaine significantly elevated approach responses to Form, while daily stress pretreatment produced a trend in the opposite direction, producing greater avoidance of Form. Preliminary

Determination of the lactone and lactone plus carboxylate forms of 9-aminocamptothecin in human plasma by sensitive high-performance liquid chromatography with fluorescence detection

NARCIS (Netherlands)

W.J. Loos (Walter); A. Sparreboom (Alex); J. Verweij (Jaap); K. Nooter (Kees); G. Stoter (Gerrit); J.H.M. Schellens (Jan)

1997-01-01

textabstractTwo sensitive reversed-phase high-performance liquid chromatographic fluorescence methods, with simple sample handling at the site of the patient, are described for the determination of the lactone and lactone plus carboxylate forms of g-aminocamptothecin (9AC). For 9AC lactone, the

Alteration in lipid composition of plasma membranes of sensitive and resistant Guerin carcinoma cells due to the action of free and liposomal form of cisplatin.

Science.gov (United States)

Naleskina, L A; Todor, I N; Nosko, M M; Lukianova, N Y; Pivnyuk, V M; Chekhun, V F

2013-09-01

To study in vivo changes of lipid composition of plasma membranes of sensitive and resistant to cisplatin Guerin carcinoma cells under influence of free and liposomal cisplatin forms. The isolation of plasma membranes from parental (sensitive) and resistant to cisplatin Guerin carcinoma cells was by differential ultracentrifugation in sucrose density gradient. Lipids were detected by method of thin-layer chromatography. It was determined that more effective action of cisplatin liposomal form on resistant cells is associated with essential abnormalities of conformation of plasma membrane due to change of lipid components and architectonics of rafts. It results in the increase of membrane fluidity. Reconstructions in lipid composition of plasma membranes of cisplatin-resistant Guerin carcinoma cells provide more intensive delivery of drug into the cells, increase of its concentration and more effective interaction with cellular structural elements.

Closed-form eigensolutions of nonviscously, nonproportionally damped systems based on continuous damping sensitivity

Science.gov (United States)

Lázaro, Mario

2018-01-01

In this paper, nonviscous, nonproportional, vibrating structures are considered. Nonviscously damped systems are characterized by dissipative mechanisms which depend on the history of the response velocities via hereditary kernel functions. Solutions of the free motion equation lead to a nonlinear eigenvalue problem involving mass, stiffness and damping matrices. Viscoelasticity leads to a frequency dependence of this latter. In this work, a novel closed-form expression to estimate complex eigenvalues is derived. The key point is to consider the damping model as perturbed by a continuous fictitious parameter. Assuming then the eigensolutions as function of this parameter, the computation of the eigenvalues sensitivity leads to an ordinary differential equation, from whose solution arises the proposed analytical formula. The resulting expression explicitly depends on the viscoelasticity (frequency derivatives of the damping function), the nonproportionality (influence of the modal damping matrix off-diagonal terms). Eigenvectors are obtained using existing methods requiring only the corresponding eigenvalue. The method is validated using a numerical example which compares proposed with exact ones and with those determined from the linear first order approximation in terms of the damping matrix. Frequency response functions are also plotted showing that the proposed approach is valid even for moderately or highly damped systems.

Yeast Ivy1p Is a Putative I-BAR-domain Protein with pH-sensitive Filament Forming Ability in vitro.

Science.gov (United States)

Itoh, Yuzuru; Kida, Kazuki; Hanawa-Suetsugu, Kyoko; Suetsugu, Shiro

2016-01-01

Bin-Amphiphysin-Rvs161/167 (BAR) domains mold lipid bilayer membranes into tubules, by forming a spiral polymer on the membrane. Most BAR domains are thought to be involved in forming membrane invaginations through their concave membrane binding surfaces, whereas some members have convex membrane binding surfaces, and thereby mold membranes into protrusions. The BAR domains with a convex surface form a subtype called the inverse BAR (I-BAR) domain or IRSp53-MIM-homology domain (IMD). Although the mammalian I-BAR domains have been studied, those from other organisms remain elusive. Here, we found putative I-BAR domains in Fungi and animal-like unicellular organisms. The fungal protein containing the putative I-BAR-domain is known as Ivy1p in yeast, and is reportedly localized in the vacuole. The phylogenetic analysis of the I-BAR domains revealed that the fungal I-BAR-domain containing proteins comprise a distinct group from those containing IRSp53 or MIM. Importantly, Ivy1p formed a polymer with a diameter of approximately 20 nm in vitro, without a lipid membrane. The filaments were formed at neutral pH, but disassembled when pH was reverted to basic. Moreover, Ivy1p and the I-BAR domain expressed in mammalian HeLa cells was localized at a vacuole-like structure as filaments as revealed by super-resolved microscopy. These data indicate the pH-sensitive polymer forming ability and the functional conservation of Ivy1p in eukaryotic cells.

Neutron electromagnetic form factors

International Nuclear Information System (INIS)

Finn, J.M.; Madey, R.; Eden, T.; Markowitz, P.; Rutt, P.M.; Beard, K.; Anderson, B.D.; Baldwin, A.R.; Keane, D.; Manley, D.M.; Watson, J.W.; Zhang, W.M.; Kowalski, S.; Bertozzi, W.; Dodson, G.; Farkhondeh, M.; Dow, K.; Korsch, W.; Tieger, D.; Turchinetz, W.; Weinstein, L.; Gross, F.; Mougey, J.; Ulmer, P.; Whitney, R.; Reichelt, T.; Chang, C.C.; Kelly, J.J.; Payerle, T.; Cameron, J.; Ni, B.; Spraker, M.; Barkhuff, D.; Lourie, R.; Verst, S.V.; Hyde-Wright, C.; Jiang, W.-D.; Flanders, B.; Pella, P.; Arenhoevel, H.

1992-01-01

Nucleon form factors provide fundamental input for nuclear structure and quark models. Current knowledge of neutron form factors, particularly the electric form factor of the neutron, is insufficient to meet these needs. Developments of high-duty-factor accelerators and polarization-transfer techniques permit new experiments that promise results with small sensitivities to nuclear models. We review the current status of the field, our own work at the MIT/Bates linear accelerator, and future experimental efforts

Sensitivity functions for uncertainty analysis: Sensitivity and uncertainty analysis of reactor performance parameters

International Nuclear Information System (INIS)

Greenspan, E.

1982-01-01

This chapter presents the mathematical basis for sensitivity functions, discusses their physical meaning and information they contain, and clarifies a number of issues concerning their application, including the definition of group sensitivities, the selection of sensitivity functions to be included in the analysis, and limitations of sensitivity theory. Examines the theoretical foundation; criticality reset sensitivities; group sensitivities and uncertainties; selection of sensitivities included in the analysis; and other uses and limitations of sensitivity functions. Gives the theoretical formulation of sensitivity functions pertaining to ''as-built'' designs for performance parameters of the form of ratios of linear flux functionals (such as reaction-rate ratios), linear adjoint functionals, bilinear functions (such as reactivity worth ratios), and for reactor reactivity. Offers a consistent procedure for reducing energy-dependent or fine-group sensitivities and uncertainties to broad group sensitivities and uncertainties. Provides illustrations of sensitivity functions as well as references to available compilations of such functions and of total sensitivities. Indicates limitations of sensitivity theory originating from the fact that this theory is based on a first-order perturbation theory

Robust dimensions of anxiety sensitivity : Development and initial validation of the anxiety sensitivity index-3

NARCIS (Netherlands)

Taylor, Steven; Zvolensky, Michael J.; Cox, Brian J.; Deacon, Brett; Heimberg, Richard G.; Ledley, Deborah Roth; Abramowitz, Jonathan S.; Holaway, Robert M.; Sandin, Bonifacio; Stewart, Sherry H.; Coles, Meredith; Eng, Winnie; Daly, Erin S.; Arrindell, Willem A.; Bouvard, Martine; Cardenas, Samuel Jurado

Accumulating evidence suggests that anxiety sensitivity (fear of arousal-related sensations) plays an important role in many clinical conditions, particularly anxiety disorders. Research has increasingly focused on how the basic dimensions of anxiety sensitivity are related to various forms of

Modulation of nucleotide sensitivity of ATP-sensitive potassium channels by phosphatidylinositol-4-phosphate 5-kinase.

Science.gov (United States)

Shyng, S L; Barbieri, A; Gumusboga, A; Cukras, C; Pike, L; Davis, J N; Stahl, P D; Nichols, C G

2000-01-18

ATP-sensitive potassium channels (K(ATP) channels) regulate cell excitability in response to metabolic changes. K(ATP) channels are formed as a complex of a sulfonylurea receptor (SURx), a member of the ATP-binding cassette protein family, and an inward rectifier K(+) channel subunit (Kir6.x). Membrane phospholipids, in particular phosphatidylinositol (PI) 4,5-bisphosphate (PIP(2)), activate K(ATP) channels and antagonize ATP inhibition of K(ATP) channels when applied to inside-out membrane patches. To examine the physiological relevance of this regulatory mechanism, we manipulated membrane PIP(2) levels by expressing either the wild-type or an inactive form of PI-4-phosphate 5-kinase (PIP5K) in COSm6 cells and examined the ATP sensitivity of coexpressed K(ATP) channels. Channels from cells expressing the wild-type PIP5K have a 6-fold lower ATP sensitivity (K(1/2), the half maximal inhibitory concentration, approximately 60 microM) than the sensitivities from control cells (K(1/2) approximately 10 microM). An inactive form of the PIP5K had little effect on the K(1/2) of wild-type channels but increased the ATP-sensitivity of a mutant K(ATP) channel that has an intrinsically lower ATP sensitivity (from K(1/2) approximately 450 microM to K(1/2) approximately 100 microM), suggesting a decrease in membrane PIP(2) levels as a consequence of a dominant-negative effect of the inactive PIP5K. These results show that PIP5K activity, which regulates PIP(2) and PI-3,4,5-P(3) levels, is a significant determinant of the physiological nucleotide sensitivity of K(ATP) channels.

A STUDY OF INTERMEDIATES INVOLVED IN THE FOLDING PATHWAY FOR RECOMBINANT HUMAN MACROPHAGE COLONY-STIMULATING FACTOR (M-CSF) - EVIDENCE FOR 2 DISTINCT FOLDING PATHWAYS

NARCIS (Netherlands)

WILKINS, JA; CONE, J; RANDHAWA, ZI; WOOD, D; WARREN, MK; WITKOWSKA, HE

The folding pathway for a 150-amino acid recombinant form of the dimeric cytokine human macrophage colony-stimulating factor (M-CSF) has been studied. All 14 cysteine residues in the biologically active homodimer are involved in disulfide linkages. The structural characteristics of folding

Purification and assay of cell-invasive form of calmodulin-sensitive adenylyl cyclase from Bordetella pertussis

International Nuclear Information System (INIS)

Masure, H.R.; Donovan, M.G.; Storm, D.R.

1991-01-01

An invasive form of the CaM-sensitive adenylyl cyclase from Bordetella pertussis can be isolated from bacterial culture supernatants. This isolation is achieved through the use of QAE-Sephadex anion-exchange chromatography. It has been demonstrated that the addition of exogenous Ca 2+ to the anion-exchange gradient buffers will affect elution from the column and will thereby affect the isolation of invasive adenylyl cyclase. This is probably due to a Ca2(+)-dependent interaction of the catalytic subunit with another component in the culture supernatant. Two peaks of adenylyl cyclase activity are obtained. The Pk1 adenylyl cyclase preparation is able to cause significant increases in intracellular cAMP levels in animal cells. This increase occurs rapidly and in a dose-dependent manner in both N1E-115 mouse neuroblastoma cells and human erythrocytes. The Pk2 adenylyl cyclase has catalytic activity but is not cell invasive. This material can serve, therefore, as a control to ensure that the cAMP which is measured is, indeed, intracellular. A second control is to add exogenous CaM to the Pk1 adenylyl cyclase preparation. The 45-kDa catalytic subunit-CaM complex is not cell invasive. Although the mechanism for membrane translocation of the adenylyl cyclase is unknown, there is evidence that the adenylyl cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis. Calmodulin-sensitive adenylyl cyclase activity can be removed from preparations of the adenylyl cyclase that have been subjected to SDS-polyacrylamide gel electrophoresis. This property of the enzyme has enabled purification of the catalytic subunit to apparent homogeneity. The purified catalytic subunit from culture supernatants has a predicted molecular weight of 45,000. This polypeptide interacts directly with Ca 2+ and this interaction may be important for its invasion into animal cells

Purification and assay of cell-invasive form of calmodulin-sensitive adenylyl cyclase from Bordetella pertussis

Energy Technology Data Exchange (ETDEWEB)

Masure, H.R.; Donovan, M.G.; Storm, D.R.

1991-01-01

An invasive form of the CaM-sensitive adenylyl cyclase from Bordetella pertussis can be isolated from bacterial culture supernatants. This isolation is achieved through the use of QAE-Sephadex anion-exchange chromatography. It has been demonstrated that the addition of exogenous Ca{sup 2}{sup +} to the anion-exchange gradient buffers will affect elution from the column and will thereby affect the isolation of invasive adenylyl cyclase. This is probably due to a Ca2(+)-dependent interaction of the catalytic subunit with another component in the culture supernatant. Two peaks of adenylyl cyclase activity are obtained. The Pk1 adenylyl cyclase preparation is able to cause significant increases in intracellular cAMP levels in animal cells. This increase occurs rapidly and in a dose-dependent manner in both N1E-115 mouse neuroblastoma cells and human erythrocytes. The Pk2 adenylyl cyclase has catalytic activity but is not cell invasive. This material can serve, therefore, as a control to ensure that the cAMP which is measured is, indeed, intracellular. A second control is to add exogenous CaM to the Pk1 adenylyl cyclase preparation. The 45-kDa catalytic subunit-CaM complex is not cell invasive. Although the mechanism for membrane translocation of the adenylyl cyclase is unknown, there is evidence that the adenylyl cyclase enters animal cells by a mechanism distinct from receptor-mediated endocytosis. Calmodulin-sensitive adenylyl cyclase activity can be removed from preparations of the adenylyl cyclase that have been subjected to SDS-polyacrylamide gel electrophoresis. This property of the enzyme has enabled purification of the catalytic subunit to apparent homogeneity. The purified catalytic subunit from culture supernatants has a predicted molecular weight of 45,000. This polypeptide interacts directly with Ca{sup 2}{sup +} and this interaction may be important for its invasion into animal cells.

Studies on the sensitivity of guinea pigs and golden hamsters irradiated with different doses of gamma rays to infections with R and S forms of Pseudomonas pseudomallei

International Nuclear Information System (INIS)

Najdenski, Kh.M.; Velyanov, D.K.

1989-01-01

Whole-body gamma irradiation was carried out on guinea pigs of both sexes with 2 Gy (sublethal dose), 2 Gy fractionated (4 x 0.5 Gy a day) and 0.5 Gy, and on golden hamsters with 6 Gy (sublethal dose) and 0.5 Gy. The animals were injected i.p. 24 h after irradiation with bacterial suspensions of P. pseudomallei R 7 and R 15 . The results showed a great increase of sensitivity to infection in the animals irradiated with sublethal dose, both as regards the R and S forms. Susceptibility rose appreciably also in guinea pigs irradiated fractionally with a dose of 2 Gy and to a relatively lower degree upon irradiation with 0.5 Gy. For the golden hamsters the sensitivity toward both investigated strains was extremely high and it remained unchanged upon irradiation with 6 Gy and 0.5 Gy. The data obtained provided grounds for the existence of a certain correlation between the different radioresistance of guinea pigs and golden hamsters and the changes established in their sensitivity to infections with R and S forms of Ps. pseudomallei after whole-body gamma irradiation

DNA Binding and Phosphorylation Regulate the Core Structure of the NF-κB p50 Transcription Factor.

Science.gov (United States)

Vonderach, Matthias; Byrne, Dominic P; Barran, Perdita E; Eyers, Patrick A; Eyers, Claire E

2018-06-05

The NF-κB transcription factors are known to be extensively phosphorylated, with dynamic site-specific modification regulating their ability to dimerize and interact with DNA. p50, the proteolytic product of p105 (NF-κB1), forms homodimers that bind DNA but lack intrinsic transactivation function, functioning as repressors of transcription from κB promoters. Here, we examine the roles of specific phosphorylation events catalysed by either protein kinase A (PKA c ) or Chk1, in regulating the functions of p50 homodimers. LC-MS/MS analysis of proteolysed p50 following in vitro phosphorylation allows us to define Ser328 and Ser337 as PKA c - and Chk1-mediated modifications, and pinpoint an additional four Chk1 phosphosites: Ser65, Thr152, Ser242 and Ser248. Native mass spectrometry (MS) reveals Chk1- and PKA c -regulated disruption of p50 homodimer formation through Ser337. Additionally, we characterise the Chk1-mediated phosphosite, Ser242, as a regulator of DNA binding, with a S242D p50 phosphomimetic exhibiting a > 10-fold reduction in DNA binding affinity. Conformational dynamics of phosphomimetic p50 variants, including S242D, are further explored using ion-mobility MS (IM-MS). Finally, comparative theoretical modelling with experimentally observed p50 conformers, in the absence and presence of DNA, reveals that the p50 homodimer undergoes conformational contraction during electrospray ionisation that is stabilised by complex formation with κB DNA. Graphical Abstract ᅟ.

Dissection of structural and functional requirements that underlie the interaction of ERdj3 protein with substrates in the endoplasmic reticulum.

Science.gov (United States)

Otero, Joel H; Lizák, Beata; Feige, Matthias J; Hendershot, Linda M

2014-10-03

ERdj3, a mammalian endoplasmic reticulum (ER) Hsp40/DnaJ family member, binds unfolded proteins, transfers them to BiP, and concomitantly stimulates BiP ATPase activity. However, the requirements for ERdj3 binding to and release from substrates in cells are not well understood. We found that ERdj3 homodimers that cannot stimulate the ATPase activity of BiP (QPD mutants) bound to unfolded ER proteins under steady state conditions in much greater amounts than wild-type ERdj3. This was due to reduced release from these substrates as opposed to enhanced binding, although in both cases dimerization was strictly required for substrate binding. Conversely, heterodimers consisting of one wild-type and one mutant ERdj3 subunit bound substrates at levels comparable with wild-type ERdj3 homodimers, demonstrating that release requires only one protomer to be functional in stimulating BiP ATPase activity. Co-expressing wild-type ERdj3 and a QPD mutant, which each exclusively formed homodimers, revealed that the release rate of wild-type ERdj3 varied according to the relative half-lives of substrates, suggesting that ERdj3 release is an important step in degradation of unfolded client proteins in the ER. Furthermore, pulse-chase experiments revealed that the binding of QPD mutant homodimers remained constant as opposed to increasing, suggesting that ERdj3 does not normally undergo reiterative binding cycles with substrates. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Formation of disulfide bonds and homodimers of the major cat allergen Fel d 1 equivalent to the natural allergen by expression in Escherichia coli.

Science.gov (United States)

Grönlund, Hans; Bergman, Tomas; Sandström, Kristofer; Alvelius, Gunvor; Reininger, Renate; Verdino, Petra; Hauswirth, Alexander; Liderot, Karin; Valent, Peter; Spitzauer, Susanne; Keller, Walter; Valenta, Rudolf; van Hage-Hamsten, Marianne

2003-10-10

Dander from the domestic cat (Felis domesticus) is one of the most common causes of IgE-mediated allergy. Attempts to produce tetrameric folded major allergen Fel d 1 by recombinant methods with structural features similar to the natural allergen have been only partially successful. In this study, a recombinant folded Fel d 1 with molecular and biological properties similar to the natural counterpart was produced. A synthetic gene coding for direct fusion of the Fel d 1 chain 2 N-terminally to chain 1 was constructed by overlapping oligonucleotides in PCR. Escherichia coli expression resulted in a non-covalently associated homodimer with an apparent molecular mass of 30 kDa defined by size exclusion chromatography. Furthermore, each 19,177-Da subunit displayed a disulfide pattern identical to that found in the natural Fel d 1, i.e. Cys3(1) Cys73(2), Cys44(1)-Cys48(2), Cys70(1)-Cys7(2), as determined by electrospray mass spectrometry after tryptic digestion. Circular dichroism analysis showed identical folds of natural and recombinant Fel d 1. Furthermore, recombinant Fel d l reacted specifically with serum IgE, inducing expression of CD203c on basophils and lymphoproliferative responses in cat-allergic patients. The results show that the overall fold and immunological properties of the recombinant Fel d 1 are very similar to those of natural Fel d 1. Moreover, the recombinant Fel d 1 construct provides a tool for defining the three-dimensional structure of Fel d 1 and represents a reagent for diagnosis and allergen-specific immunotherapy of cat allergy.

Regulation of follitropin-sensitive adenylate cyclase by stimulatory and inhibitory forms of the guanine nucleotide regulatory protein in immature rat Sertoli cells

International Nuclear Information System (INIS)

Johnson, G.P.

1987-01-01

Studies have been designed to examine the role of guanine nucleotides in mediating FSH-sensitive adenylate cyclase activity in Sertoli cell plasma membranes. Analysis of [ 3 H]GDP binding to plasma membranes suggested a single high affinity site with a K d = 0.24 uM. Competition studies indicated that GTP γ S was 7-fold more potent than GDP β S. Bound GDP could be released by FSH in the presence of GTP γ S, but not by FSH alone. Adenylate cyclase activity was enhanced 5-fold by FSH in the presence of GTP. Addition of GDP β S to the activated enzyme (FSH plus GTP) resulted in a time-dependent decay to basal activity within 20 sec. GDP β S competitively inhibited GTP γ S-stimulated adenylate cyclase activity with a K i = 0.18 uM. Adenylate cyclase activity was also demonstrated to be sensitive to the nucleotide bound state. In the presence of FSH, only the GTP γ S-bound form persisted even if GDP β S previously occupied all available binding sites. Two membrane proteins, M r = 43,000 and 48,000, were ADP·ribosylated using cholera toxin and labeling was enhanced 2 to 4-fold by GTP γ S but not by GDP β S. The M r = 43,000 and 48,000 proteins represented variant forms of G S . A single protein of M r = 40,000 (G i ) was ADP-ribosylated by pertussis toxin in vitro. GTP inhibited forskolin-stimulated adenylate cyclase activity with an IC 50 = 0.1 uM. The adenosine analog, N 6 ·phenylisopropyl adenosine enhanced GTP inhibition of forskolin-stimulated adenylate cyclase activity by an additional 15%. GTP-dependent inhibition of forskolin-sensitive adenylate cyclase activity was abolished in membranes prepared from Sertoli cells treated in culture with pertussis toxin

Nucleon Form Factors Using Spin Degrees of Freedom

International Nuclear Information System (INIS)

Jones, Mark

2002-01-01

An overview of recent measurements of the neutron and proton electromagnetic form factors from double polarization experiments. Spin observables are sensitive to the product of nucleon form factor which allows access to the small nucleon electric form factors

Structural basis of the 9-fold symmetry of centrioles.

Science.gov (United States)

Kitagawa, Daiju; Vakonakis, Ioannis; Olieric, Natacha; Hilbert, Manuel; Keller, Debora; Olieric, Vincent; Bortfeld, Miriam; Erat, Michèle C; Flückiger, Isabelle; Gönczy, Pierre; Steinmetz, Michel O

2011-02-04

The centriole, and the related basal body, is an ancient organelle characterized by a universal 9-fold radial symmetry and is critical for generating cilia, flagella, and centrosomes. The mechanisms directing centriole formation are incompletely understood and represent a fundamental open question in biology. Here, we demonstrate that the centriolar protein SAS-6 forms rod-shaped homodimers that interact through their N-terminal domains to form oligomers. We establish that such oligomerization is essential for centriole formation in C. elegans and human cells. We further generate a structural model of the related protein Bld12p from C. reinhardtii, in which nine homodimers assemble into a ring from which nine coiled-coil rods radiate outward. Moreover, we demonstrate that recombinant Bld12p self-assembles into structures akin to the central hub of the cartwheel, which serves as a scaffold for centriole formation. Overall, our findings establish a structural basis for the universal 9-fold symmetry of centrioles. Copyright © 2011 Elsevier Inc. All rights reserved.

A retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensitivity in transcriptional activation of the lactoferrin gene.

Science.gov (United States)

Lee, M O; Liu, Y; Zhang, X K

1995-08-01

The lactoferrin gene is highly expressed in many different tissues, and its expression is controlled by different regulators. In this report, we have defined a retinoic acid response element (RARE) in the 5'-flanking region of the lactoferrin gene promoter. The lactoferrin-RARE is composed of two AGGTCA-like motifs arranged as a direct repeat with 1-bp spacing (DR-1). A gel retardation assay demonstrated that it bound strongly with retinoid X receptor (RXR) homodimers and RXR-retinoic acid receptor (RAR) heterodimers as well as chicken ovalbumin upstream promoter transcription factor (COUP-TF) orphan receptor. In CV-1 cells, the lactoferrin-RARE linked with a heterologous thymidine kinase promoter was strongly activated by RXR homodimers in response to 9-cis-retinoic acid (9-cis-RA) but not to all-trans-RA. When the COUP-TF orphan receptor was cotransfected, the 9-cis-RA-induced RXR homodimer activity was strongly repressed. A unique feature of the lactoferrin-RARE is that it has an AGGTCA-like motif in common with an estrogen-responsive element (ERE). The composite RARE/ERE contributes to the functional interaction between retinoid receptors and the estrogen receptor (ER) and their ligands. In CV-1 cells, cotransfection of the retinoid and estrogen receptors led to mutual inhibition of the other's activity, while an RA-dependent inhibition of ER activity was observed in breast cancer cells. Furthermore, the lactoferrin-RARE/ERE showed differential transactivation activity in different cell types. RAs could activate the lactoferrin-RARE/ERE in human leukemia HL-60 cells and U937 cells but not in human breast cancer cells. By gel retardation analyses, we demonstrated that strong binding of the endogenous COUP-TF in breast cancer cells to the composite element contributed to diminished RA response in these cells. Thus, the lactoferrin-RARE/ERE functions as a signaling switch module that mediates multihormonal responsiveness in the regulation of lactoferrin gene

The properties of B-form monoamine oxidase in mitochondria from monkey platelet.

Science.gov (United States)

Obata, Toshio; Aomine, Masahiro

The present study was examined the effect of the properties of monkey platelet monoamine oxidase (MAO) based on inhibitor sensitivity. Monkey platelet showed a high MAO activity with beta-phenylethylamine (beta-PEA) as substrate and a very low A-form MAO activity with 5 hydroxytryptamine (5-HT) as substrate. Moreover, monkey platelet MAO was sensitive to the drugs deprenyl as B-form MAO inhibitor and less sensitive to clorgyline and harmaline as A form MAO inhibitor with beta-PEA as the B-form MAO substrate. B-form MAO from monkey platelet was more stable against heat treatment at 55 degrees C than B-form MAO in brain. After digestion with trypsin at 37 degrees C for 4 hrs, it was found that MAO from platelet was inhibited about 70% with beta-PEA as substrate with brain. The tricyclic antidepressant imipramine and nortriptyline inhibited B-form MAO activity more potency than B-form MAO in brain. However, when the noncyclic antidepressant nomifensine was used, monkey platelet B-form MAO activities were less potently inhibited. All these reagents were noncompetitive inhibitors of B form MAO in monkey platelet. The present studies demonstrated that monkey platelet MAO is a single of B-form MAO and sensitive to tricyclic antidepressants.

ANTISTAPHYLOCOCCAL ACTIVITY OF LIPOSOMAL FORMS OF LINCOMYCIN

Directory of Open Access Journals (Sweden)

Derkach SA

2015-04-01

Full Text Available Nowadays the vital problem of modern medicine is a tendency to emerging of both nosocomial and community-acquired strains before antibiotic resistance forming. The complexity of antibiotic therapy of diseases caused by methicillin resistant staphylococci having high poly resistance almost to every classes of antibacterial agents is of prime importance. One of the ways to improve antibacterial preparations still remains the development of their liposomal forms. This work studies antistaphylococcal activity (according to MIC of the liposomal form of lincomycin developed in the Institute of Dermatology and Venereology of Ukraine by Ivanova N. N., the Candidate of Сhemical Sciences.The purpose of this research work was to study liposomal inhibiting concentration of the liposomalny form of lincomycin and a commercial preparation lincomycin (produced by CJSC “Pharmaceutical firm "Darnitsa". Determination of the minimum inhibiting concentration was carried out by a tablet micromethod by consecutive cultivations of the samples under study.It is shown that MIC of liposomal lincomycin is eight times as low as usual lincomycin (0,23mkg/ml to 1,87 mkg/ml. Antibacterial activity of the liposomal form of lincomycin is studied concerning the patients selected from the different biotopes with pyo inflammatory diseases of staphylococcus strains (15 strains – methicillin sensitive, 12 strains - methicillin resistant.It is shown authentically the higher sensitivity of S. aureus strains to the liposomal form of lincomycin in comparison with usual lincomycin . Also 50.0% of MRSA strains were sensitive to the liposomalny form of lincomycin that shows the perspective for the development of the liposomal forms of antibiotics to cure staphylococcal infections.

Restoration of glycoprotein Erns dimerization via pseudoreversion partially restores virulence of classical swine fever virus.

Science.gov (United States)

Tucakov, Anna Katharina; Yavuz, Sabine; Schürmann, Eva-Maria; Mischler, Manjula; Klingebeil, Anne; Meyers, Gregor

2018-01-01

The classical swine fever virus (CSFV) represents one of the most important pathogens of swine. The CSFV glycoprotein E rns is an essential structural protein and an important virulence factor. The latter is dependent on the RNase activity of this envelope protein and, most likely, its secretion from the infected cell. A further important feature with regard to its function as a virulence factor is the formation of disulfide-linked E rns homodimers that are found in virus-infected cells and virions. Mutant CSFV lacking cysteine (Cys) 171, the residue responsible for intermolecular disulfide bond formation, were found to be attenuated in pigs (Tews BA, Schürmann EM, Meyers G. J Virol 2009;83:4823-4834). In the course of an animal experiment with such a dimerization-negative CSFV mutant, viruses were reisolated from pigs that contained a mutation of serine (Ser) 209 to Cys. This mutation restored the ability to form disulphide-linked E rns homodimers. In transient expression studies E rns mutants carrying the S209C change were found to form homodimers with about wt efficiency. Also the secretion level of the mutated proteins was equivalent to that of wt E rns . Virus mutants containing the Cys171Ser/Ser209Cys configuration exhibited wt growth rates and increased virulence when compared with the Cys171Ser mutant. These results provide further support for the connection between CSFV virulence and E rns dimerization.

Diverse oligomeric states of CEACAM IgV domains.

Science.gov (United States)

Bonsor, Daniel A; Günther, Sebastian; Beadenkopf, Robert; Beckett, Dorothy; Sundberg, Eric J

2015-11-03

Carcinoembryonic antigen-related cell adhesion molecules (CEACAMs) comprise a large family of cell surface adhesion molecules that bind to themselves and other family members to carry out numerous cellular functions, including proliferation, signaling, differentiation, tumor suppression, and survival. They also play diverse and significant roles in immunity and infection. The formation of CEACAM oligomers is caused predominantly by interactions between their N-terminal IgV domains. Although X-ray crystal structures of CEACAM IgV domain homodimers have been described, how CEACAMs form heterodimers or remain monomers is poorly understood. To address this key aspect of CEACAM function, we determined the crystal structures of IgV domains that form a homodimeric CEACAM6 complex, monomeric CEACAM8, and a heterodimeric CEACAM6-CEACAM8 complex. To confirm and quantify these interactions in solution, we used analytical ultracentrifugation to measure the dimerization constants of CEACAM homodimers and isothermal titration calorimetry to determine the thermodynamic parameters and binding affinities of CEACAM heterodimers. We found the CEACAM6-CEACAM8 heterodimeric state to be substantially favored energetically relative to the CEACAM6 homodimer. Our data provide a molecular basis for the adoption of the diverse oligomeric states known to exist for CEACAMs and suggest ways in which CEACAM6 and CEACAM8 regulate the biological functions of one another, as well as of additional CEACAMs with which they interact, both in cis and in trans.

A systematic evaluation of protein kinase a-a-kinase anchoring protein interaction motifs

NARCIS (Netherlands)

Burgers, Pepijn P|info:eu-repo/dai/nl/341566551; van der Heyden, Marcel A G; Kok, Bart; Heck, Albert J R|info:eu-repo/dai/nl/105189332; Scholten, Arjen|info:eu-repo/dai/nl/313939780

2015-01-01

Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

A systematic evaluation of protein kinase A-A-kinase anchoring protein interaction motifs

NARCIS (Netherlands)

Burgers, Pepijn P; van der Heyden, MAG; Kok, Bart; Heck, Albert J R; Scholten, Arjen

2015-01-01

Protein kinase A (PKA) in vertebrates is localized to specific locations in the cell via A-kinase anchoring proteins (AKAPs). The regulatory subunits of the four PKA isoforms (RIα, RIβ, RIIα, and RIIβ) each form a homodimer, and their dimerization domain interacts with a small helical region present

Sensitivity analysis of respiratory parameter uncertainties: impact of criterion function form and constraints.

Science.gov (United States)

Lutchen, K R

1990-08-01

A sensitivity analysis based on weighted least-squares regression is presented to evaluate alternative methods for fitting lumped-parameter models to respiratory impedance data. The goal is to maintain parameter accuracy simultaneously with practical experiment design. The analysis focuses on predicting parameter uncertainties using a linearized approximation for joint confidence regions. Applications are with four-element parallel and viscoelastic models for 0.125- to 4-Hz data and a six-element model with separate tissue and airway properties for input and transfer impedance data from 2-64 Hz. The criterion function form was evaluated by comparing parameter uncertainties when data are fit as magnitude and phase, dynamic resistance and compliance, or real and imaginary parts of input impedance. The proper choice of weighting can make all three criterion variables comparable. For the six-element model, parameter uncertainties were predicted when both input impedance and transfer impedance are acquired and fit simultaneously. A fit to both data sets from 4 to 64 Hz could reduce parameter estimate uncertainties considerably from those achievable by fitting either alone. For the four-element models, use of an independent, but noisy, measure of static compliance was assessed as a constraint on model parameters. This may allow acceptable parameter uncertainties for a minimum frequency of 0.275-0.375 Hz rather than 0.125 Hz. This reduces data acquisition requirements from a 16- to a 5.33- to 8-s breath holding period. These results are approximations, and the impact of using the linearized approximation for the confidence regions is discussed.

Correlation of radiation sensitivity and nitrofurantoin sensitivity of Escherichia coli K-12

International Nuclear Information System (INIS)

Kloeck, K.

1981-01-01

The Uvr- and rec-mutants of E.coli K-12 have been tested with a view to their radiation- and nitrofuration sensitivity. The tests showed that all mutants tested were more radiation- and NF-sensitive than the wild type AB 1157. When the NF-sensitivity had been compared to the UV- and X-ray sensitivity it became obvious that the NF-sensitivity is correlated to the UV-sensitivity. Studies carried out with regard to the time dependence of the NF-effect on E.coli showed that the effect of NF on E. Coli became weaker after about 1 1/2 to 2 hours. That is possibly caused by the fact that the E. coli bacteria succeed in reducing the NF to an inactive form. By means of nitrosoguanidine mutants of E-coli AB 1157 had been induced and by means of the Replicite Plating Method, NF-sensible mutants had been isolated from the plutonium mixture. Among the mutants which had been isolated by this method, 74% had been more UV-sensitive than the wild type and 55% more X-ray sensitive. Thus NF-sensitive mutants have not necessarily to be considered as rec-mutants as there are also uvr-mutants in the mixture. (orig.) [de

Calmodulin affects sensitization of Drosophila melanogaster odorant receptors

Directory of Open Access Journals (Sweden)

Latha eMukunda

2016-02-01

Full Text Available Flying insects have developed a remarkably sensitive olfactory system to detect faint and turbulent odor traces. This ability is linked to the olfactory receptors class of odorant receptors (ORs, occurring exclusively in winged insects. ORs form heteromeric complexes of an odorant specific receptor protein (OrX and a highly conserved co-receptor protein (Orco. The ORs form ligand gated ion channels that are tuned by intracellular signaling systems. Repetitive subthreshold odor stimulation of olfactory sensory neurons sensitizes insect ORs. This OR sensitization process requires Orco activity. In the present study we first asked whether OR sensitization can be monitored with heterologously expressed OR proteins. Using electrophysiological and calcium imaging methods we demonstrate that D. melanogaster OR proteins expressed in CHO cells show sensitization upon repeated weak stimulation. This was found for OR channels formed by Orco as well as by Or22a or Or56a and Orco. Moreover, we show that inhibition of calmodulin (CaM action on OR proteins, expressed in CHO cells, abolishes any sensitization. Finally, we investigated the sensitization phenomenon using an ex vivo preparation of olfactory sensory neurons (OSNs expressing Or22a inside the fly’s antenna. Using calcium imaging, we observed sensitization in the dendrites as well as in the soma. Inhibition of calmodulin with W7 disrupted the sensitization within the outer dendritic shaft, whereas the sensitization remained in the other OSN compartments. Taken together, our results suggest that CaM action is involved in sensitizing the OR complex and that this mechanisms accounts for the sensitization in the outer dendrites, whereas further mechanisms contribute to the sensitization observed in the other OSN compartments. The use of heterologously expressed OR proteins appears to be suitable for further investigations on the mechanistic basis of OR sensitization, while investigations on native

Psychometric properties of the Bulgarian translation of noise sensitivity scale short form (NSS-SF): implementation in the field of noise control.

Science.gov (United States)

Dzhambov, Angel M; Dimitrova, Donka D

2014-01-01

The Noise Sensitivity Scale Short Form (NSS-SF), developed in English as a more practical form of the classical Weinstein NSS, has not to date been validated in other cultures, and its validity and reliability have not yet been confirmed. This study aimed to validate NSS-SF in Bulgarian and to demonstrate its applicability. The study comprised test-retest (n = 115) and a field-testing (n = 71) of the newly validated scale. Its construct validity was examined with confirmatory factor analysis, and very good model-fit was observed. Temporal stability was assessed in a test-retest (r = 0.990), convergent validity was examined with single-item susceptibility to the noise scale (r = 0.906) and discriminant validity was confirmed with single-item noise annoyance scale (r = 0.718). The lowest observed McDonald's omega across the studies was 0.923. The cross-cultural validation of NSS-SF was successful but it proved to be somewhat problematic with respect to its annoyance-based items.

Spectroscopic and functional characterization of iron-bound forms of Azotobacter vinelandii (Nif)IscA.

Science.gov (United States)

Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

2012-10-16

The ability of Azotobacter vinelandii(Nif)IscA to bind Fe has been investigated to assess the role of Fe-bound forms in NIF-specific Fe-S cluster biogenesis. (Nif)IscA is shown to bind one Fe(III) or one Fe(II) per homodimer and the spectroscopic and redox properties of both the Fe(III)- and Fe(II)-bound forms have been characterized using the UV-visible absorption, circular dichroism, and variable-temperature magnetic circular dichroism, electron paramagnetic resonance, Mössbauer and resonance Raman spectroscopies. The results reveal a rhombic intermediate-spin (S = 3/2) Fe(III) center (E/D = 0.33, D = 3.5 ± 1.5 cm(-1)) that is most likely 5-coordinate with two or three cysteinate ligands and a rhombic high spin (S = 2) Fe(II) center (E/D = 0.28, D = 7.6 cm(-1)) with properties similar to reduced rubredoxins or rubredoxin variants with three cysteinate and one or two oxygenic ligands. Iron-bound (Nif)IscA undergoes reversible redox cycling between the Fe(III)/Fe(II) forms with a midpoint potential of +36 ± 15 mV at pH 7.8 (versus NHE). l-Cysteine is effective in mediating release of free Fe(II) from both the Fe(II)- and Fe(III)-bound forms of (Nif)IscA. Fe(III)-bound (Nif)IscA was also shown to be a competent iron source for in vitro NifS-mediated [2Fe-2S] cluster assembly on the N-terminal domain of NifU, but the reaction occurs via cysteine-mediated release of free Fe(II) rather than direct iron transfer. The proposed roles of A-type proteins in storing Fe under aerobic growth conditions and serving as iron donors for cluster assembly on U-type scaffold proteins or maturation of biological [4Fe-4S] centers are discussed in light of these results.

Magnetic form factors of the trinucleons

Energy Technology Data Exchange (ETDEWEB)

Schiavilla, R; Pandharipande, V R; Riska, Dan-Olof

1989-11-01

The magnetic form factors of ³H and ³He are calculated with the Monte Carlo method from variational ground-state wave functions obtained for the Argonne and Urbana two- and three-nucleon interactions. The electromagnetic current operator contains one- and two-body terms that are constructed so as to satisfy the continuity equation with the two-nucleon potential in the Hamiltonian. The results obtained with the Argonne two-nucleon interaction are in overall agreement with the empirical values. It appears that the remaining theoretical uncertainty, in the calculation of these form factors from a given interaction model, is dominated by that in the electromagnetic form factors of the nucleon. It is found that the isovector magnetic form factors are rather sensitive to the details of the isospin-dependent tensor force, and they are much better reproduced with the Argonne than the Urbana potential. The isoscalar magnetic form factors appear to be sensitive to the spin-orbit interactions, and are better reproduced with the Urbana potential. The Argonne potential has a stronger τ1∙τ2 tensor force, while the Urbana one has a shorter-range spin-orbit interaction.

Sensitive Media

Directory of Open Access Journals (Sweden)

Malinowska Anna

2017-12-01

Full Text Available The paper engages with what we refer to as “sensitive media,” a concept associated with developments in the overall media environment, our relationships with media devices, and the quality of the media themselves. Those developments point to the increasing emotionality of the media world and its infrastructures. Mapping the trajectories of technological development and impact that the newer media exert on human condition, our analysis touches upon various forms of emergent affect, emotion, and feeling in order to trace the histories and motivations of the sensitization of “the media things” as well as the redefinition of our affective and emotional experiences through technologies that themselves “feel.”

Cold denaturation of the HIV-1 protease monomer

DEFF Research Database (Denmark)

Rösner, Heike Ilona; Caldarini, Martina; Prestel, Andreas

2017-01-01

The HIV-1-protease is a complex protein which in its active form adopts a homodimer dominated by -sheet structures. We have discovered a cold-denatured state of the monomeric subunit of HIV-1-protease which is populated above 0ºC and therefore directly accessible to various spectroscopic approac...

Activation of non-sensitizing or low-sensitizing fragrance substances into potent sensitizers - prehaptens and prohaptens.

Science.gov (United States)

Karlberg, Ann-Therese; Börje, Anna; Duus Johansen, Jeanne; Lidén, Carola; Rastogi, Suresh; Roberts, David; Uter, Wolfgang; White, Ian R

2013-12-01

Experimental and clinical studies have shown that fragrance substances can act as prehaptens or prohaptens. They form allergens that are more potent than the parent substance by activation outside or in the skin via abiotic (chemical and physical factors) and/or biotic activation, thus, increasing the risk of sensitization. In the present review a series of fragrance substances with well documented abiotic and/or biotic activation are given as indicative and illustrative examples of the general problem. Commonly used fragrance substances, also found in essential oils, autoxidize on contact with air, forming potent sensitizers that can be an important source for contact allergy to fragrances and fragranced products. Some of them can act as prohaptens and be activated in the skin as well. The experimental findings are confirmed in large clinical studies. When substances with structural alerts for acting as prohaptens and/or prehaptens are identified, the possibility of generating new potent allergens should be considered. Predictive testing should include activation steps. Further experimental and clinical research regarding activation of fragrance substances is needed to increase consumer safety. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Development of EMab-51, a Sensitive and Specific Anti-Epidermal Growth Factor Receptor Monoclonal Antibody in Flow Cytometry, Western Blot, and Immunohistochemistry.

Science.gov (United States)

Itai, Shunsuke; Kaneko, Mika K; Fujii, Yuki; Yamada, Shinji; Nakamura, Takuro; Yanaka, Miyuki; Saidoh, Noriko; Handa, Saori; Chang, Yao-Wen; Suzuki, Hiroyoshi; Harada, Hiroyuki; Kato, Yukinari

2017-10-01

The epidermal growth factor receptor (EGFR) is a member of the human epidermal growth factor receptor (HER) family of receptor tyrosine kinases and is involved in cell growth and differentiation. EGFR homodimers or heterodimers with other HER members, such as HER2 and HER3, activate downstream signaling cascades in many cancers. In this study, we developed novel anti-EGFR monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses. First, we expressed the full-length or ectodomain of EGFR in LN229 glioblastoma cells and then immunized mice with LN229/EGFR or ectodomain of EGFR, and performed the first screening using enzyme-linked immunosorbent assays. Subsequently, we selected mAbs according to their efficacy in flow cytometry (second screening), Western blot (third screening), and immunohistochemical (fourth screening) analyses. Among 100 mAbs, only one clone EMab-51 (IgG 1 , kappa) reacted with EGFR in Western blot analysis. Finally, immunohistochemical analyses with EMab-51 showed sensitive and specific reactions against oral cancer cells, warranting the use of EMab-51 to detect EGFR in pathological analyses of EGFR-expressing cancers.

Sensitivity test of parameterizations of subgrid-scale orographic form drag in the NCAR CESM1

Science.gov (United States)

Liang, Yishuang; Wang, Lanning; Zhang, Guang Jun; Wu, Qizhong

2017-05-01

Turbulent drag caused by subgrid orographic form drag has significant effects on the atmosphere. It is represented through parameterization in large-scale numerical prediction models. An indirect parameterization scheme, the Turbulent Mountain Stress scheme (TMS), is currently used in the National Center for Atmospheric Research Community Earth System Model v1.0.4. In this study we test a direct scheme referred to as BBW04 (Beljaars et al. in Q J R Meteorol Soc 130:1327-1347, 10.1256/qj.03.73), which has been used in several short-term weather forecast models and earth system models. Results indicate that both the indirect and direct schemes increase surface wind stress and improve the model's performance in simulating low-level wind speed over complex orography compared to the simulation without subgrid orographic effect. It is shown that the TMS scheme produces a more intense wind speed adjustment, leading to lower wind speed near the surface. The low-level wind speed by the BBW04 scheme agrees better with the ERA-Interim reanalysis and is more sensitive to complex orography as a direct method. Further, the TMS scheme increases the 2-m temperature and planetary boundary layer height over large areas of tropical and subtropical Northern Hemisphere land.

Malachite green mediates homodimerization of antibody VL domains to form a fluorescent ternary complex with singular symmetric interfaces

Science.gov (United States)

Szent-Gyorgyi, Chris; Stanfield, Robyn L.; Andreko, Susan; Dempsey, Alison; Ahmed, Mushtaq; Capek, Sara; Waggoner, Alan; Wilson, Ian A.; Bruchez, Marcel P.

2013-01-01

We report that a symmetric small molecule ligand mediates the assembly of antibody light chain variable domains (VLs) into a correspondent symmetric ternary complex with novel interfaces. The L5* Fluorogen Activating Protein (FAP) is a VL domain that binds malachite green dye (MG) to activate intense fluorescence. Crystallography of liganded L5* reveals a 2:1 protein:ligand complex with inclusive C2 symmetry, where MG is almost entirely encapsulated between an antiparallel arrangement of the two VL domains. Unliganded L5* VL domains crystallize as a similar antiparallel VL/VL homodimer. The complementarity determining regions (CDRs) are spatially oriented to form novel VL/VL and VL/ligand interfaces that tightly constrain a propeller conformer of MG. Binding equilibrium analysis suggests highly cooperative assembly to form a very stable VL/MG/VL complex, such that MG behaves as a strong chemical inducer of dimerization. Fusion of two VL domains into a single protein tightens MG binding over 1,000-fold to low picomolar affinity without altering the large binding enthalpy, suggesting that bonding interactions with ligand and restriction of domain movements make independent contributions to binding. Fluorescence activation of a symmetrical fluorogen provides a selection mechanism for the isolation and directed evolution of ternary complexes where unnatural symmetric binding interfaces are favored over canonical antibody interfaces. As exemplified by L5*, these self-reporting complexes may be useful as modulators of protein association or as high affinity protein tags and capture reagents. PMID:23978698

Properties and crystal structure of methylenetetrahydrofolate reductase from Thermus thermophilus HB8.

Directory of Open Access Journals (Sweden)

Sayaka Igari

Full Text Available Methylenetetrahydrofolate reductase (MTHFR is one of the enzymes involved in homocysteine metabolism. Despite considerable genetic and clinical attention, the reaction mechanism and regulation of this enzyme are not fully understood because of difficult production and poor stability. While recombinant enzymes from thermophilic organisms are often stable and easy to prepare, properties of thermostable MTHFRs have not yet been reported.MTHFR from Thermus thermophilus HB8, a homologue of Escherichia coli MetF, has been expressed in E. coli and purified. The purified MTHFR was chiefly obtained as a heterodimer of apo- and holo-subunits, that is, one flavin adenine dinucleotide (FAD prosthetic group bound per dimer. The crystal structure of the holo-subunit was quite similar to the β(8α(8 barrel of E. coli MTHFR, while that of the apo-subunit was a previously unobserved closed form. In addition, the intersubunit interface of the dimer in the crystals was different from any of the subunit interfaces of the tetramer of E. coli MTHFR. Free FAD could be incorporated into the apo-subunit of the purified Thermus enzyme after purification, forming a homodimer of holo-subunits. Comparison of the crystal structures of the heterodimer and the homodimer revealed different intersubunit interfaces, indicating a large conformational change upon FAD binding. Most of the biochemical properties of the heterodimer and the homodimer were the same, except that the homodimer showed ≈50% activity per FAD-bound subunit in folate-dependent reactions.The different intersubunit interfaces and rearrangement of subunits of Thermus MTHFR may be related to human enzyme properties, such as the allosteric regulation by S-adenosylmethionine and the enhanced instability of the Ala222Val mutant upon loss of FAD. Whereas E. coli MTHFR was the only structural model for human MTHFR to date, our findings suggest that Thermus MTHFR will be another useful model for this important enzyme.

Relative sensitivity of formability to anisotropy

International Nuclear Information System (INIS)

Logan, R.W.; Maker, B.N.

1997-01-01

This work compares the relative importance of material anisotropy in sheet forming as compared to other material and process variables. The comparison is made quantitative by the use of normalized dependencies of depth to failure (forming limit is reached) on various measures of anisotropy, as well as strain and rate sensitivity, friction, and tooling. Comparisons are made for a variety of forming processes examined previously in the literature as well as two examples of complex stampings in this work. 7 The examples rover a range from nearly pure draw to nearly pure stretch situations, and show that for materials following a quadratic yield criterion, anisotropy is among the most sensitive parameters influencing formability. For materials following higher-exponent yield criteria, the dependency is milder but is still of the order of most other process parameters. However, depending on the particular forming operation, it is shown that in some cases anisotropy may be ignored, whereas in others its consideration is crucial to a good quality analysis

Radiation-sensitive diacrylates

International Nuclear Information System (INIS)

Demajistre, R.

1976-01-01

Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysts to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials. 6 claims, no drawings

Marrow hypoplasia: a rare complication of untreated Grave's disease.

Science.gov (United States)

Garcia, Juliana; França, Larissa de; Ellinger, Vivian; Wolff, Mônica

2014-12-01

Atypical presentation forms of hyperthyroidism are always a challenge to the clinician. We present a female patient with the typical symptoms of thyrotoxicosis, without any thionamides treatment before, associated with pancytopenia, which recovered after euthyroidism state was achieved. Although the major cases of pancytopenia in Grave's disease are seen as a complication of antithyroid drugs (thioamides), in this case report the alteration in blood tests was associated with untreated hyperthyroidism. In the literature review, we found 19 case reports between 1981 to 2012, but it has been related to a hypercellular bone marrow with periferic destruction. Our case, however, is about a hypocellular bone marrow without fibrosis or fat tissue replacement, which proceeded with a periferic improvement following thyroid treatment. Although rare, pancytopenia, when present, may develop as an unusual and severe manifestation in untreated subjects.

On the sensitivity of IMRT dose optimization to the mathematical form of a biological imaging-based prescription function

International Nuclear Information System (INIS)

Bowen, Stephen R; Bentzen, Soeren M; Jeraj, Robert; Flynn, Ryan T

2009-01-01

Voxel-based prescriptions of deliberately non-uniform dose distributions based on molecular imaging, so-called dose painting or theragnostic radiation therapy, require specification of a transformation that maps the image data intensities to prescribed doses. However, the functional form of this transformation is currently unknown. An investigation into the sensitivity of optimized dose distributions resulting from several possible prescription functions was conducted. Transformations between the radiotracer activity concentrations from Cu-ATSM PET images, as a surrogate of tumour hypoxia, and dose prescriptions were implemented to yield weighted distributions of prescribed dose boosts in high uptake regions. Dose escalation was constrained to reflect clinically realistic whole tumour doses and constant normal tissue doses. Optimized heterogeneous dose distributions were found by minimizing a voxel-by-voxel quadratic objective function in which all tumour voxels were given equal weight. Prescriptions based on a polynomial mapping function were found to be least constraining on their optimized plans, while prescriptions based on a sigmoid mapping function were the most demanding to deliver. A prescription formalism that fixed integral dose was less sensitive to errors in the choice of the mapping function than one that boosted integral dose. Integral doses to normal tissue and critical structures were insensitive to the shape of the prescription function. Planned target dose conformity improved with smaller beamlet dimensions until the inherent spatial resolution of the functional image was matched. Clinical implementation of dose painting depends on advances in absolute quantification of functional images and improvements in delivery techniques over smaller spatial scales.

Thermal sensitivity and thermally enhanced radiosensitivity of murine bone marrow granulocyte-macrophage colony-forming units (CFU-GM)

International Nuclear Information System (INIS)

Yoshida, Hiroshi

1994-01-01

This study was to evaluate thermal response of granulocyte-macrophage colony-forming unit (CFU-GM) in vitro and to investigate the difference of thermally enhanced radiosensitivity on cell survivals of CFU-GM between in vitro and in vivo. In in vitro heating exposure, bone marrow suspensions, obtained from mouse femora or tibiae, were incubated; and in vivo heating exposure, the lower half-body of mice were immersed in a circulating hot water bath. For irradiation schedules, cell suspensions were irradiated in vitro or in vivo (whole-body irradiation). Thermal sensitivity curve, obtained by in vivo heating exposure, showed a shoulder region at short exposures followed by an exponential decline during longer heating exposures. The Arrhenius curve showed a break at 42.3deg C and inactivation enthalpy was 1836 kJ/mol (438 kcal/mole) below the break point and 704 kJ/mole (168 kcal/mole) above the point. When bone marrow suspensions, obtained after either in vitro or in vivo irradiation, were heated in vitro at 42deg C for 60 min, supura-additive effect on cell survivals was observed by in vivo irradiation, but not observed by in vitro irradiation. Thermal enhancement ratio (TER), defined as D 0 of combined in vivo irradiation and in vitro heating divided by D 0 of the sole in vivo irradiation, was 1.12. In vivo heating following in vivo irradiation also showed supra-additive effect, giving TER of 1.66. These findings indicated that murine marrow CFU-GM is sensitive to hyperthermia and that thermal radiosensitization is never negligible when hyperthermia is employed with preceding X-irradiation. Thus, combined use of radiotherapy and hyperthermia may decrease bone marrow function. (N.K.)

The roles of the RIIβ linker and N-terminal cyclic nucleotide-binding domain in determining the unique structures of the type IIβ protein kinase A: a small angle x-ray and neutron scattering study.

Science.gov (United States)

Blumenthal, Donald K; Copps, Jeffrey; Smith-Nguyen, Eric V; Zhang, Ping; Heller, William T; Taylor, Susan S

2014-10-10

Protein kinase A (PKA) is ubiquitously expressed and is responsible for regulating many important cellular functions in response to changes in intracellular cAMP concentrations. The PKA holoenzyme is a tetramer (R2:C2), with a regulatory subunit homodimer (R2) that binds and inhibits two catalytic (C) subunits; binding of cAMP to the regulatory subunit homodimer causes activation of the catalytic subunits. Four different R subunit isoforms exist in mammalian cells, and these confer different structural features, subcellular localization, and biochemical properties upon the PKA holoenzymes they form. The holoenzyme containing RIIβ is structurally unique in that the type IIβ holoenzyme is much more compact than the free RIIβ homodimer. We have used small angle x-ray scattering and small angle neutron scattering to study the solution structure and subunit organization of a holoenzyme containing an RIIβ C-terminal deletion mutant (RIIβ(1-280)), which is missing the C-terminal cAMP-binding domain to better understand the structural organization of the type IIβ holoenzyme and the RIIβ domains that contribute to stabilizing the holoenzyme conformation. Our results demonstrate that compaction of the type IIβ holoenzyme does not require the C-terminal cAMP-binding domain but rather involves large structural rearrangements within the linker and N-terminal cyclic nucleotide-binding domain of the RIIβ homodimer. The structural rearrangements are significantly greater than seen previously with RIIα and are likely to be important in mediating short range and long range interdomain and intersubunit interactions that uniquely regulate the activity of the type IIβ isoform of PKA. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Validated sensitive spectrofluorimetric method for determination of antihistaminic drug azelastine HCl in pure form and in pharmaceutical dosage forms: application to stability study.

Science.gov (United States)

El-Masry, Amal A; Hammouda, Mohammed E A; El-Wasseef, Dalia R; El-Ashry, Saadia M

2017-03-01

A highly sensitive, simple and rapid spectrofluorimetric method was developed for the determination of azelastine HCl (AZL) in either its pure state or pharmaceutical dosage form. The proposed method was based on measuring the native fluorescence of the studied drug in 0.2 M H 2 SO 4 at λ em  = 364 nm after excitation at λ ex  = 275 nm. Different experimental parameters were studied and optimized carefully to obtain the highest fluorescence intensity. The proposed method showed a linear dependence of the fluorescence intensity on drug concentration over a concentration range of 10-250 ng/mL, with a limit of detection of 1.52 ng/mL and limit of quantitation of 4.61 ng/mL. Moreover, the method was successfully applied to pharmaceutical preparations, with percent recovery values (± SD) of 99.96 (± 0.4) and 100.1 (± 0.52) for nasal spray and eye drops, respectively. The results were in good agreement with those obtained by the comparison method, as revealed by Student's t-test and the variance ratio F-test. The method was extended to study the stability of AZL under stress conditions, where the drug was exposed to neutral, acidic, alkaline, oxidative and photolytic degradation according to International Conference on Harmonization (ICH) guidelines. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster

DEFF Research Database (Denmark)

Vognsen, Tina Reinholdt; Kristensen, Ole

2012-01-01

The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a ß-sheet and three a-helices forming...

Electromagnetic form factors

International Nuclear Information System (INIS)

Desplanques, B.

1987-01-01

Electromagnetic form factors, in first approximation, are sensitive to spatial distribution of nucleons and to their current. In second approximation, more precise effects are concerned, whose role is increasing with momentum transfer and participating essentially of short range nuclei description. They concern of course the nucleon-nucleon interaction while approaching each other and keeping their free-state identity, but also mutually polarizing one the other. In this last effect, radial and orbital excitations of nucleon, the nucleon mesonic cloud modification and the nucleon antinucleon pair excitation are included. In this paper, these contributions are discussed while trying to find the important elements for a good description of form factors. Current questions are also discussed. Light nuclei are essentially concerned [fr

Spectrophotometric determination of pizotefin maleate in pure form ...

African Journals Online (AJOL)

Two simple, quick and sensitive methods were described for the spectrophotometric determination of pizotefin maleate (PZT) either in pure form or pharmaceutical form (tablets). The methods were based on the reaction of pizotefin maleate as 'n' electron donor with chloranilic acid (p-CLA) and 7,7,8 ...

A retinoic acid response element that overlaps an estrogen response element mediates multihormonal sensitivity in transcriptional activation of the lactoferrin gene.

OpenAIRE

Lee, M O; Liu, Y; Zhang, X K

1995-01-01

The lactoferrin gene is highly expressed in many different tissues, and its expression is controlled by different regulators. In this report, we have defined a retinoic acid response element (RARE) in the 5'-flanking region of the lactoferrin gene promoter. The lactoferrin-RARE is composed of two AGGTCA-like motifs arranged as a direct repeat with 1-bp spacing (DR-1). A gel retardation assay demonstrated that it bound strongly with retinoid X receptor (RXR) homodimers and RXR-retinoic acid re...

Ozone-forming potential of reformulated gasoline

National Research Council Canada - National Science Library

Committee on Ozone-Forming Potential of Reformulated Gasoline, National Research Council

...) technical aspects of various air-quality issues related to RFG assessment, and (3) the sensitivity of evaluations of the relative ozone-forming potentials to factors related to fuel properties and the variability of vehicle technologies and driving patterns.

16 kDa heat shock protein from heat-inactivated Mycobacterium tuberculosis is a homodimer - suitability for diagnostic applications with specific llama VHH monoclonals.

Directory of Open Access Journals (Sweden)

Saurabh K Srivastava

Full Text Available BACKGROUND: The 16 kDa heat shock protein (HSP is an immuno-dominant antigen, used in diagnosis of infectious Mycobacterium tuberculosis (M.tb. causing tuberculosis (TB. Its use in serum-based diagnostics is limited, but for the direct identification of M.tb. bacteria in sputum or cultures it may represent a useful tool. Recently, a broad set of twelve 16 kDa specific heavy chain llama antibodies (VHH has been isolated, and their utility for diagnostic applications was explored. METHODOLOGY/PRINCIPAL FINDINGS: To identify the epitopes recognized by the nine (randomly selected from a set of twelve 16 kDa specific VHH antibodies distinct VHH antibodies, 14 overlapping linear epitopes (each 20 amino acid long were characterized using direct and sandwich ELISA techniques. Seven out of 14 epitopes were recognized by 8 out of 9 VHH antibodies. The two highest affinity binders B-F10 and A-23 were found to bind distinct epitopes. Sandwich ELISA and SPR experiments showed that only B-F10 was suitable as secondary antibody with both B-F10 and A-23 as anchoring antibodies. To explain this behavior, the epitopes were matched to the putative 3D structure model. Electrospray ionization time-of-flight mass spectrometry and size exclusion chromatography were used to determine the higher order conformation. A homodimer model best explained the differential immunological reactivity of A-23 and B-F10 against heat-treated M.tb. lysates. CONCLUSIONS/SIGNIFICANCE: The concentrations of secreted antigens of M.tb. in sputum are too low for immunological detection and existing kits are only used for identifying M.tb. in cultures. Here we describe how specific combinations of VHH domains could be used to detect the intracellular HSP antigen. Linked to methods of pre-concentrating M.tb. cells prior to lysis, HSP detection may enable the development of protein-based diagnostics of sputum samples and earlier diagnosis of diseases.

A review of treatment options for Graves' disease: why total thyroidectomy is a viable option in selected patients.

Science.gov (United States)

Mohan, Vinuta; Lind, Robert

2016-01-01

Graves' disease is the most common cause of hyperthyroidism. If left untreated, patients may have multiple systemic complications such as cardiac, reproductive, and skeletal disease. Thionamides, such as methimazole and propylthiouracil, and I(131) iodine ablation are the most commonly prescribed treatment for Graves' disease. Total thyroidectomy is often overlooked for treatment and is usually only offered if the other options have failed. In our case, we discuss a patient who was admitted to our medical center with symptomatic hyperthyroidism secondary to long-standing Graves' disease. She had a history of non-compliance with medications and medical clinic follow-up. The risks and benefits of total thyroidectomy were explained and she consented to surgery. A few months after the procedure, she was biochemically and clinically euthyroid on levothyroxine. She had no further emergency room visits or admissions for uncontrolled thyroid disease. Here we review the advantages and disadvantages of the more typically prescribed treatments, thionamides and I(131)iodine ablation. We also review the importance of shared decision making and the benefits of total thyroidectomy for the management of Graves' disease. Given the improvement in surgical techniques over the past decade and a significant reduction of complications, we suggest total thyroidectomy be recommended more often for patients with Graves' disease.

Methimazole associated eosinophilic pleural effusion: a case report.

Science.gov (United States)

Gaspar-da-Costa, Pedro; Duarte Silva, Filipa; Henriques, Júlia; do Vale, Sónia; Braz, Sandra; Meneses Santos, João; M M Victorino, Rui

2017-03-21

Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.

Sensitivity analysis in multi-parameter probabilistic systems

International Nuclear Information System (INIS)

Walker, J.R.

1987-01-01

Probabilistic methods involving the use of multi-parameter Monte Carlo analysis can be applied to a wide range of engineering systems. The output from the Monte Carlo analysis is a probabilistic estimate of the system consequence, which can vary spatially and temporally. Sensitivity analysis aims to examine how the output consequence is influenced by the input parameter values. Sensitivity analysis provides the necessary information so that the engineering properties of the system can be optimized. This report details a package of sensitivity analysis techniques that together form an integrated methodology for the sensitivity analysis of probabilistic systems. The techniques have known confidence limits and can be applied to a wide range of engineering problems. The sensitivity analysis methodology is illustrated by performing the sensitivity analysis of the MCROC rock microcracking model

Phase-sensitive flow cytometer

Energy Technology Data Exchange (ETDEWEB)

Steinkamp, J.A.

1992-12-31

This report describes phase-sensitive flow cytometer (FCM) which provides additional FCM capability to use the fluorescence lifetime of one or more fluorochromes bound to single cells to provide additional information regarding the cells. The resulting fluorescence emission can be resolved into individual fluorescence signals if two fluorochromes are present or can be converted directly to a decay lifetime from a single fluorochrome. The excitation light for the fluorochromes is modulated to produce an amplitude modulated fluorescence pulse as the fluorochrome is excited in the FCM. The modulation signal also forms a reference signal that is phase-shifted a selected amount for subsequent mixing with the output modulated fluorescence intensity signal in phase-sensitive detection circuitry. The output from the phase-sensitive circuitry is then an individual resolved fluorochrome signal or a single fluorochrome decay lifetime, depending on the applied phase shifts.

Preparation of mesoporous titanium dioxide anode by a film- and pore-forming agent for the dye-sensitized solar cell

Energy Technology Data Exchange (ETDEWEB)

Hou, Wenjing; Xiao, Yaoming, E-mail: ymxiao@sxu.edu.cn; Han, Gaoyi, E-mail: han_gaoyis@sxu.edu.cn; Zhou, Haihan; Chang, Yunzhen; Zhang, Ying

2016-04-15

Highlights: • PVP is used as a film- and pore-forming agent to prepare the mesoporous TiO{sub 2} anode. • The TiO{sub 2} anode supplies high surface area for the dye adsorption. • The DSSC efficiency is strongly dependent on the pore properties of the TiO{sub 2} anode. • The DSSC efficiency with the TiO{sub 2} anode prepared by 20 wt% PVP reaches 8.39%. - Abstract: A novel mean of generating mesoporous titanium dioxide (TiO{sub 2}) anodes by employing polyvinylpyrrolidone (PVP) as the film- and pore-forming agent are proposed for dye-sensitized solar cells (DSSCs). The influences on the morphology and photovoltaic performances of the TiO{sub 2} anodes are investigated by adjusting the PVP content in synthesizing the mesoporous TiO{sub 2} anodes. The photovoltaic conversion efficiency of the DSSC is found to be strongly dependent on the pore properties of the TiO{sub 2} anode. After the sintering process, the removal of the PVP leaves porously interconnected channel structures inside the TiO{sub 2} anode, supplying enhanced specific surface area for the dye adsorption as well as the efficient electron transmission. As a result, the TiO{sub 2} anode prepared by 20 wt% PVP presents the highest performances, based on which the DSSC achieves the highest conversion efficiency of 8.39%, approximately increased by 56.53% than that of the DSSC fabricated without PVP (5.36%).

Silicon nanowire structures as high-sensitive pH-sensors

International Nuclear Information System (INIS)

Belostotskaya, S O; Chuyko, O V; Kuznetsov, A E; Kuznetsov, E V; Rybachek, E N

2012-01-01

Sensitive elements for pH-sensors created on silicon nanostructures were researched. Silicon nanostructures have been used as ion-sensitive field effect transistor (ISFET) for the measurement of solution pH. Silicon nanostructures have been fabricated by 'top-down' approach and have been studied as pH sensitive elements. Nanowires have the higher sensitivity. It was shown, that sensitive element, which is made of 'one-dimensional' silicon nanostructure have bigger pH-sensitivity as compared with 'two-dimensional' structure. Integrated element formed from two p- and n-type nanowire ISFET ('inverter') can be used as high sensitivity sensor for local relative change [H+] concentration in very small volume.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations

OpenAIRE

D?nciulescu Miulescu, R; Car?ote, M; Trif?nescu, R; Ferechide, D; Poian?, C

2013-01-01

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multip...

DEFINITION OF ETIOLOGICAL ANTIBIOTIC SENSITIVITY FACTORS IN PURULENT-INFLAMMATORY PROCESSES.

Science.gov (United States)

Dubovyk, O; Mishyna, М; Malanchuk, S; Kuzmenko, A; Kozlov, O

2017-10-01

The purpose of the study - assessment of purulent-inflammatory processes etiologic factors and determination of microbial agents' in forms of plankton and biofilms sensitivity to antibiotics. Clinical microbial strains isolated from patients with purulent-inflammatory processes were the subject of the study. The study material comprised of wound tissue, pus, bandage and suture, catheters and drainage devices. Sensitivity of isolates to antimicrobial preparations with various mechanism of activity on the microbial cells was studied with the help of micro-test system. Formation of biofilms was studied with the help of definition of bacteria strains ability to adhesion to the surface of polystyrene flatbeds. It was revealed that one of the leading factors of purulent-inflammatory process development is S.aureus, which disseminated in 36,5% of cases; E.coli disseminated in 17,3% of cases. Among the agents of purulent-inflammatory processes the specific gravity attributed to: Proteus spp. - 14,6%, S.рyogenes - 12,8%, P.aeruginosa - 6,9%, K.pneumoniae - 6,7%. It was revealed that all isolates formed dense biofilms. It was demonstrated that most isolates in plankton form were sensitive to Novapime, Cefepime, Gatifloxacin, Imipenem; sensitive strains were registered in a smaller quantity to Gentamicin, Clindamycin and Doxycycline. In terms of sensitivity of isolates in the form of biofilm to antibacterial preparations it was revealed that most isolates were polyresistant to them. Thus, the study of the sensitivity of allotted microbial strains to antimicrobial preparations demonstrated, that there were strains among cultures with multiple resistances which was the consequence of a wide and not always effective use of antimicrobial preparations.

How victim sensitivity leads to uncooperative behavior via expectancies of injustice

Directory of Open Access Journals (Sweden)

Simona eMaltese

2016-01-01

Full Text Available According to the Sensitivity-to-mean-intentions (SeMI model, dispositional victim sensitivity involves a suspicious mindset that is activated by situational cues and guides subsequent information processing and behavior like a schema. Study 1 tested whether victim-sensitive persons are more prone to form expectancies of injustice in ambiguous situations and whether these expectancies mediate the relationship between victim sensitivity and cooperation behavior in a trust game. Results show an indirect effect of victim sensitivity on cooperation after unfair treatment (vs control condition, mediated by expectancies of injustice. In Study 2 we directly manipulated the tendency to form expectancies of injustice in ambiguous situations to test for causality. Results confirmed that the readiness to expect unjust outcomes led to lower cooperation, compared to a control condition. These findings provide direct evidence that expectancy tendencies are implicated in elevated victim sensitivity and are of theoretical and practical relevance.

Sequential designs for sensitivity analysis of functional inputs in computer experiments

International Nuclear Information System (INIS)

Fruth, J.; Roustant, O.; Kuhnt, S.

2015-01-01

Computer experiments are nowadays commonly used to analyze industrial processes aiming at achieving a wanted outcome. Sensitivity analysis plays an important role in exploring the actual impact of adjustable parameters on the response variable. In this work we focus on sensitivity analysis of a scalar-valued output of a time-consuming computer code depending on scalar and functional input parameters. We investigate a sequential methodology, based on piecewise constant functions and sequential bifurcation, which is both economical and fully interpretable. The new approach is applied to a sheet metal forming problem in three sequential steps, resulting in new insights into the behavior of the forming process over time. - Highlights: • Sensitivity analysis method for functional and scalar inputs is presented. • We focus on the discovery of most influential parts of the functional domain. • We investigate economical sequential methodology based on piecewise constant functions. • Normalized sensitivity indices are introduced and investigated theoretically. • Successful application to sheet metal forming on two functional inputs

Accurate and sensitive quantification of protein-DNA binding affinity.

Science.gov (United States)

Rastogi, Chaitanya; Rube, H Tomas; Kribelbauer, Judith F; Crocker, Justin; Loker, Ryan E; Martini, Gabriella D; Laptenko, Oleg; Freed-Pastor, William A; Prives, Carol; Stern, David L; Mann, Richard S; Bussemaker, Harmen J

2018-04-17

Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes. Copyright © 2018 the Author(s). Published by PNAS.

Hipertiroidismo por doença de Graves durante a gestação Hyperthyroidism due to Graves' disease during pregnancy

Directory of Open Access Journals (Sweden)

Carla Amaral de Almeida

2005-05-01

pregnant women with hyperthyroidism due to Graves' disease. These women were evaluated through TSH and serum free T4 at each trimester or four weeks after setting thionamide dosage. The goal was to maintain free T4 in the superior third of the normal range using the lowest possible thionamide dose. RESULTS: the mean age at the beginning of the pregnancy was 31.1 years (23 to 41. The mean dosage of thionamide was reduced in eight pregnancies (69.5% and, in two, the drug was discontinued. Before pregnancy, mean propylthiouracil dose was 400 mg/day (200-900 and mean methimazole dose was 45 mg/day (20-60. After delivery, antithyroid drug dose was 200 and 30 mg/day, respectively. One patient presented premature labor (at 36 weeks and another, a newborn small for gestational age (2.000 g at 38 weeks. There was one stillborn. There were no miscarriages or congenital anomalies. After labor, antithyroid drug dose was increased in seven patients and in the others the dose was maintained. CONCLUSIONS: we suggest close follow-up of pregnant women with hyperthyroidism and progressive reduction of thionamide dose during pregnancy to avoid maternal hypothyroidism and its consequences to fetal development. After labor, these women must be evaluated regarding their thyroid function because hyperthyroidism can worsen. Thionamide use is safe for the patients and their offspring.

Measuring value sensitivity in medicine.

Science.gov (United States)

Ineichen, Christian; Christen, Markus; Tanner, Carmen

2017-01-28

Value sensitivity - the ability to recognize value-related issues when they arise in practice - is an indispensable competence for medical practitioners to enter decision-making processes related to ethical questions. However, the psychological competence of value sensitivity is seldom an explicit subject in the training of medical professionals. In this contribution, we outline the traditional concept of moral sensitivity in medicine and its revised form conceptualized as value sensitivity and we propose an instrument that measures value sensitivity. We developed an instrument for assessing the sensitivity for three value groups (moral-related values, values related to the principles of biomedical ethics, strategy-related values) in a four step procedure: 1) value identification (n = 317); 2) value representation (n = 317); 3) vignette construction and quality evaluation (n = 37); and 4) instrument validation by comparing nursing professionals with hospital managers (n = 48). We find that nursing professionals recognize and ascribe importance to principle-related issues more than professionals from hospital management. The latter are more likely to recognize and ascribe importance to strategy-related issues. These hypothesis-driven results demonstrate the discriminatory power of our newly developed instrument, which makes it useful not only for health care professionals in practice but for students and people working in the clinical context as well.

Sensitive spectrophotometric determination of metoclopramide hydrochloride in dosage forms and spiked human urine using vanillin

Directory of Open Access Journals (Sweden)

O. Zenita Devi

2016-09-01

Full Text Available A new spectrophotometric method which is simple, sensitive, selective and rapid is described for the determination of metoclopramide hydrochloride (MCP in bulk drug and in dosage forms using vanillin as the chromogenic agent. The method is based on the condensation reaction between primary aromatic amine group present in MCP with aromatic aldehyde, vanillin to produce an intense yellow colored product. The resulting Schiff’s base shows an absorption maximum at 410 nm and the reaction product is stable for more than one day. The reaction was carried out in acetic acid and perchloric acid medium. Beer’s law was obeyed in the concentration range 1.5–15.0 μg ml−1 MCP with a molar absorptivity of 1.89 × 104 l mol−1 cm−1. The limit of detection (LOD and limit of quantification (LOQ were found to be 0.51 and 1.55 μg ml−1, respectively. The method was statistically evaluated by calculating percent relative error (% RE for accuracy and percent relative standard deviation (% RSD for precision, and was applied successfully to the determination of MCP in tablets, in injection and also in spiked human urine. No interference was observed from common additives found in pharmaceutical preparations. The results obtained by the proposed method were validated statistically by comparing the results with those of the reference method by applying the Student’s t-test and F-test. The accuracy and reliability of the method were further ascertained by performing recovery tests via standard-addition technique.

Endogenous Opioid-Masked Latent Pain Sensitization

DEFF Research Database (Denmark)

Pereira, Manuel P; Donahue, Renee R; Dahl, Jørgen B

2015-01-01

UNLABELLED: Following the resolution of a severe inflammatory injury in rodents, administration of mu-opioid receptor inverse agonists leads to reinstatement of pain hypersensitivity. The mechanisms underlying this form of latent pain sensitization (LS) likely contribute to the development of chr...

Optimization and control of metal forming processes

NARCIS (Netherlands)

Havinga, Gosse Tjipke

2016-01-01

Inevitable variations in process and material properties limit the accuracy of metal forming processes. Robust optimization methods or control systems can be used to improve the production accuracy. Robust optimization methods are used to design production processes with low sensitivity to the

Utility of Hantzsch reaction for development of highly sensitive spectrofluorimetric method for determination of alfuzosin and terazosin in bulk, dosage forms and human plasma.

Science.gov (United States)

Hammad, Mohamed A; Omar, Mahmoud A; Salman, Baher I

2017-09-01

A highly sensitive, cheap, simple and accurate spectrofluorimetric method has been developed and validated for the determination of alfuzosin hydrochloride and terazosin hydrochloride in their pharmaceutical dosage forms and in human plasma. The developed method is based on the reaction of the primary amine moiety in the studied drugs with acetylacetone and formaldehyde according to the Hantzsch reaction, producing yellow fluorescent products that can be measured spectrofluorimetrically at 480 nm after excitation at 415 nm. Different experimental parameters affecting the development and stability of the reaction products were carefully studied and optimized. The fluorescence-concentration plots of alfuzosin and terazosin were rectilinear over a concentration range of 70-900 ng ml -1 , with quantitation limits 27.1 and 32.2 ng ml -1 for alfuzosin and terazosin, respectively. The proposed method was validated according to ICH guidelines and successfully applied to the analysis of the investigated drugs in dosage forms, content uniformity test and spiked human plasma with high accuracy. Copyright © 2017 John Wiley & Sons, Ltd.

New insights into the organization of plasma membrane and its role in signal transduction.

Science.gov (United States)

Suzuki, Kenichi G N

2015-01-01

Plasma membranes have heterogeneous structures for efficient signal transduction, required to perform cell functions. Recent evidence indicates that the heterogeneous structures are produced by (1) compartmentalization by actin-based membrane skeleton, (2) raft domains, (3) receptor-receptor interactions, and (4) the binding of receptors to cytoskeletal proteins. This chapter provides an overview of recent studies on diffusion, clustering, raft association, actin binding, and signal transduction of membrane receptors, especially glycosylphosphatidylinositol (GPI)-anchored receptors. Studies on diffusion of GPI-anchored receptors suggest that rafts may be small and/or short-lived in plasma membranes. In steady state conditions, GPI-anchored receptors form transient homodimers, which may represent the "standby state" for the stable homodimers and oligomers upon ligation. Furthermore, It is proposed that upon ligation, the binding of GPI-anchored receptor clusters to cytoskeletal actin filaments produces a platform for downstream signaling, and that the pulse-like signaling easily maintains the stability of the overall signaling activity. Copyright © 2015 Elsevier Inc. All rights reserved.

Stability and Sensitive Analysis of a Model with Delay Quorum Sensing

Directory of Open Access Journals (Sweden)

Zhonghua Zhang

2015-01-01

Full Text Available This paper formulates a delay model characterizing the competition between bacteria and immune system. The center manifold reduction method and the normal form theory due to Faria and Magalhaes are used to compute the normal form of the model, and the stability of two nonhyperbolic equilibria is discussed. Sensitivity analysis suggests that the growth rate of bacteria is the most sensitive parameter of the threshold parameter R0 and should be targeted in the controlling strategies.

Pseudoscalar form factors in tau-neutrino nucleon scattering

International Nuclear Information System (INIS)

Hagiwara, K.; Mawatari, K.; Yokoya, H.

2004-01-01

We investigate the pseudoscalar transition form factors of nucleon for quasi-elastic scattering and Δ resonance production in tau-neutrino nucleon scattering via the charged current interactions. Although the pseudoscalar form factors play an important role for the τ production in neutrino-nucleon scattering, these are not known well. In this Letter, we examine their effects in quasi-elastic scattering and Δ resonance production and find that the cross section, Q 2 distribution, and spin polarization of the produced τ ± leptons are quite sensitive to the pseudoscalar form factors

Immune suppression with supraoptimal doses of antigen in contact sensitivity. I. Demonstration of suppressor cells and their sensitivity to cyclophosphamide.

Science.gov (United States)

Sy, M S; Miller, S D; Claman, H N

1977-07-01

Immunologic suppression was induced in a mouse model of contact sensitization to DNFB by using supraoptimal doses of antigen. In these studies, in vivo measurement of ear swelling as an indication of immunologic responsiveness correlated well with measurement of in vitro antigen-induced cell proliferation. This unresponsiveness was specific, since supraoptimal doses of DNFB did not interfere with the development of contact sensitivity to another contactant, oxazolone. The decrease in responsiveness is a form of active suppression, as lymphoid cells from supraoptimally sensitized donors transferred suppression to normal recipients. Furthermore, pretreatment with cyclophosphamide (Cy) reversed the suppression seen in supraoptimally sensitized animals but had no effect on the optimal sensitization regimen. These results indicate that supraoptimal doses of contactants can activate suppressor cells and that precursors of these cells are sensitive to Cy. Such suppressors regenerate within 7 to 14 days after Cy treatment. The ability of Cy pretreatment to affect supraoptimal sensitization without affecting optimal sensitization confirms other reports indicating that the observed results of Cy treatment depend critically upon the dose of antigen used.

Elevated Serum Fibroblast Growth Factor 21 Levels in Patients With Hyperthyroidism.

Science.gov (United States)

Xiao, Fangsen; Lin, Mingzhu; Huang, Peiying; Zeng, Jinyang; Zeng, Xin; Zhang, Huijie; Li, Xiaoying; Yang, Shuyu; Li, Zhibin; Li, Xuejun

2015-10-01

Recent evidence from animal studies indicates that fibroblast growth factor 21 (FGF21), an endocrine hormone that regulates glucose, lipid metabolism, and energy homeostasis, is regulated by T3. However, the role of FGF21 in hyperthyroid patients is unknown. The objective was to study serum FGF21 levels in hyperthyroid patients and the association of serum FGF21 levels with hyperthyroidism. This was a case-control study. A total of 119 hyperthyroid patients and 108 healthy subjects were recruited. Of them, 41 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism was obtained. Serum FGF21 levels were determined using the ELISA method. Serum FGF21 levels were significantly elevated in hyperthyroid patients as compared with normal subjects [median 290.67 (interquartile range, 156.60-502.33) vs 228.10 (169.85.25-320.10) pg/mL; P treatment, serum FGF21 levels in hyperthyroid patients declined markedly from 249.10 (139.10-444.00) to 106.90 (38.70-196.15) pg/mL (P hyperthyroidism. With adjustment for potential confounders, serum FGF21 remained independently associated with hyperthyroidism, with an adjusted odds ratio of 3.123 (95% confidence interval, 1.306-7.468) (P = .010). Serum FGF21 levels were elevated in patients with hyperthyroidism and declined after thionamide treatment. And serum FGF21 level was independently associated with hyperthyroidism.

Sensitization of in vitro mammalian cells by nitrous oxide

International Nuclear Information System (INIS)

Ewing, D.

1984-01-01

Powers and his colleagues showed almost ten years ago that sensitization by nitrous oxide required two radiolytic products: OH radicals and hydrogen peroxide. That observation with bacterial spores has been confirmed and extended with spores and several strains of bacteria. OH must be present to form hydrogen peroxide, but, in addition, OH must also be present with the hydrogen peroxide for damage to occur. (Reagent hydrogen peroxide, except at very high concentrations, will not sensitize unless OH radicals are present.) The authors have now tested nitrous oxide with two Chinese hamster cell lines, V79 and CHO. The responses in nitrogen and nitrous oxide are the same for each. The authors have tentatively concluded that insufficient hydrogen peroxide is formed in the cells' suspending fluid for damage from nitrous oxide to occur. Several results support this conclusion: reagent hydrogen peroxide is a potent sensitizer of either cell line tested in nitrogen or nitrous oxide and an assay for radiolytic hydrogen peroxide confirms that only minimal levels are formed at the doses used in these survival curves. The authors also present results of other tests to further complement work with procaryotic cells

Sensitivity Analysis Based on Markovian Integration by Parts Formula

Directory of Open Access Journals (Sweden)

Yongsheng Hang

2017-10-01

Full Text Available Sensitivity analysis is widely applied in financial risk management and engineering; it describes the variations brought by the changes of parameters. Since the integration by parts technique for Markov chains is well developed in recent years, in this paper we apply it for computation of sensitivity and show the closed-form expressions for two commonly-used time-continuous Markovian models. By comparison, we conclude that our approach outperforms the existing technique of computing sensitivity on Markovian models.

Angle sensitive single photon avalanche diode

Energy Technology Data Exchange (ETDEWEB)

Lee, Changhyuk, E-mail: cl678@cornell.edu; Johnson, Ben, E-mail: bcj25@cornell.edu; Molnar, Alyosha, E-mail: am699@cornell.edu [Electrical and Computer Engineering, Cornell University, Ithaca, New York 14850 (United States)

2015-06-08

An ideal light sensor would provide exact information on intensity, timing, location, and angle of incoming photons. Single photon avalanche diodes (SPADs) provide such desired high (single photon) sensitivity with precise time information and can be implemented at a pixel-scale to form an array to extract spatial information. Furthermore, recent work has demonstrated photodiode-based structures (combined with micro-lenses or diffraction gratings) that are capable of encoding both spatial and angular information of incident light. In this letter, we describe the implementation of such a grating structure on SPADs to realize a pixel-scale angle-sensitive single photon avalanche diode (A-SPAD) built in a standard CMOS process. While the underlying SPAD structure provides high sensitivity, the time information of the two layers of diffraction gratings above offers angle-sensitivity. Such a unique combination of SPAD and diffraction gratings expands the sensing dimensions to pave a path towards lens-less 3-D imaging and light-field time-of-flight imaging.

Usher protein functions in hair cells and photoreceptors

OpenAIRE

Cosgrove, Dominic; Zallocchi, Marisa

2013-01-01

The 10 different genes associated with the deaf/blind disorder, Usher syndrome, encode a number of structurally and functionally distinct proteins, most expressed as multiple isoforms/protein variants. Functional characterization of these proteins suggests a role in stereocilia development in cochlear hair cells, likely owing to adhesive interactions in hair bundles. In mature hair cells, homodimers of the Usher cadherins, cadherin 23 and protocadherin 15, interact to form a structural fiber,...

Isolation and characteristics of minute plaque forming mutant of cyanophage AS-1

International Nuclear Information System (INIS)

Amla, D.V.

1981-01-01

Minute plaque forming mutant (m) of cyanophage AS-1 infecting unicellular blue-green algae was isolated spontaneously and after mutagenic treatment. Compared to wild type m mutant formed small plaques, adsorption rate was slow and the burst-size was significantly decreased with prolonged eclipse and latent period. The plaque forming ability of mutant phage was sensitive to pH, heat, EDTA shock, distilled water and photosensitisation with acriflavine whereas ultraviolet sensitivity of free and intracellular phage was identical to the parent. The spontaneous reversion frequencies of mutant phage to wild type were between 10 -5 to 10 -3 and appeared to be clonal property. Reversion studies suggested possibilities of frame-shift or base-pair substitution for m mutation. (author)

Reliable Mechanochemistry: Protocols for Reproducible Outcomes of Neat and Liquid Assisted Ball-mill Grinding Experiments.

Science.gov (United States)

Belenguer, Ana M; Lampronti, Giulio I; Sanders, Jeremy K M

2018-01-23

The equilibrium outcomes of ball mill grinding can dramatically change as a function of even tiny variations in the experimental conditions such as the presence of very small amounts of added solvent. To reproducibly and accurately capture this sensitivity, the experimentalist needs to carefully consider every single factor that can affect the ball mill grinding reaction under investigation, from ensuring the grinding jars are clean and dry before use, to accurately adding the stoichiometry of the starting materials, to validating that the delivery of solvent volume is accurate, to ensuring that the interaction between the solvent and the powder is well understood and, if necessary, a specific soaking time is added to the procedure. Preliminary kinetic studies are essential to determine the necessary milling time to achieve equilibrium. Only then can exquisite phase composition curves be obtained as a function of the solvent concentration under ball mill liquid assisted grinding (LAG). By using strict and careful procedures analogous to the ones here presented, such milling equilibrium curves can be obtained for virtually all milling systems. The system we use to demonstrate these procedures is a disulfide exchange reaction starting from the equimolar mixture of two homodimers to obtain at equilibrium quantitative heterodimer. The latter is formed by ball mill grinding as two different polymorphs, Form A and Form B. The ratio R = [Form B] / ([Form A] + [Form B]) at milling equilibrium depends on the nature and concentration of the solvent in the milling jar.

Coordinate sensitive detectors based on microchannel plates

International Nuclear Information System (INIS)

Gruntman, M.A.

1984-01-01

Coordinate-sensitive detectors (CSD) on the basis of microchannel plates permit to determine in a digital form the coordinates of every recorded particle and they are used in different fields of physical experiment. The sensitive surface diameter of such detectors can reach 10 cm, and spatial resolution - 10 μm. In the review provided CSD with microchannel plates are classified according to the ways of coordinate determination, different types of the detectors, pecUliarities of their design and electron flowsheet are described. It is pointed out that there are reasons for introduction of CSD into practice of laboratory physical investigations in various fields, where the particle recorded is electron or is able to form a secondary electron. It is attributed to nuclear physics, physics of electron and atom collisions, optics, mass-spectrometry, electron microscopy, X-ray analysis, investigation of surfaces

Correlated evolution of short wavelength sensitive photoreceptor sensitivity and color pattern in Lake Malawi cichlids

Directory of Open Access Journals (Sweden)

Michael J. Pauers

2016-02-01

Full Text Available For evolutionary ecologists, the holy grail of visual ecology is to establish an unambiguous link between photoreceptor sensitivity, the spectral environment, and the perception of specific visual stimuli (e.g., mates, food, predators, etc.. Due to the bright nuptial colors of the males, and the role female mate choice plays in their evolution, the haplochromine cichlid fishes of the African great lakes are favorite research subjects for such investigations. Despite this attention, current evidence is equivocal; while distinct correlations among photoreceptor sensitivity, photic environment, and male coloration exist in Lake Victorian haplochromines, attempts to find such correlations in Lake Malawian cichlids have failed. Lake Malawi haplochromines have a wide variability in their short-wavelength-sensitive photoreceptors, especially compared to their mid- and long-wavelength-sensitive photoreceptors; these cichlids also vary in the degree to which they express one of three basic color patterns (vertical bars, horizontal stripes, and solid patches of colors, each of which is likely used in a different form of communication. Thus, we hypothesize that, in these fishes, spectral sensitivity and color pattern have evolved in a correlated fashion to maximize visual communication; specifically, ultraviolet sensitivity should be found in vertically-barred species to promote ‘private’ communication, while striped species should be less likely to have ultraviolet sensitivity, since their color pattern carries ‘public’ information. Using phylogenetic independent contrasts, we found that barred species had strong sensitivity to ultraviolet wavelengths, but that striped species typically lacked sensitivity to ultraviolet light. Further, the only variable, even when environmental variables were simultaneously considered, that could predict ultraviolet sensitivity was color pattern. We also found that, using models of correlated evolution, color

A two-dimensional low energy gamma-ray position sensitive detector

International Nuclear Information System (INIS)

Charalambous, P.M.; Dean, A.J.; Drane, M.; Gil, A.; Stephen, J.B.; Young, N.G.S.; Barbareschi, L.; Perotti, F.; Villa, G.; Badiali, M.; La Padula, C.; Polcaro, F.; Ubertini, P.

1984-01-01

An array of 1-dimensional position sensitive detectors designed to operate over the photon energy range 0.2-10.0 MeV, so as to form an efficient 2-dimensional position sensitive detection plane is described. A series of experimental tests has been carried out to evaluate and confirm the computed capabilities. (orig.)

The Sensitivity of State Differential Game Vessel Traffic Model

Directory of Open Access Journals (Sweden)

Lisowski Józef

2016-04-01

Full Text Available The paper presents the application of the theory of deterministic sensitivity control systems for sensitivity analysis implemented to game control systems of moving objects, such as ships, airplanes and cars. The sensitivity of parametric model of game ship control process in collision situations have been presented. First-order and k-th order sensitivity functions of parametric model of process control are described. The structure of the game ship control system in collision situations and the mathematical model of game control process in the form of state equations, are given. Characteristics of sensitivity functions of the game ship control process model on the basis of computer simulation in Matlab/Simulink software have been presented. In the end, have been given proposals regarding the use of sensitivity analysis to practical synthesis of computer-aided system navigator in potential collision situations.

The impact of recreational MDMA 'ecstasy' use on global form processing.

Science.gov (United States)

White, Claire; Edwards, Mark; Brown, John; Bell, Jason

2014-11-01

The ability to integrate local orientation information into a global form percept was investigated in long-term ecstasy users. Evidence suggests that ecstasy disrupts the serotonin system, with the visual areas of the brain being particularly susceptible. Previous research has found altered orientation processing in the primary visual area (V1) of users, thought to be due to disrupted serotonin-mediated lateral inhibition. The current study aimed to investigate whether orientation deficits extend to higher visual areas involved in global form processing. Forty-five participants completed a psychophysical (Glass pattern) study allowing an investigation into the mechanisms underlying global form processing and sensitivity to changes in the offset of the stimuli (jitter). A subgroup of polydrug-ecstasy users (n=6) with high ecstasy use had significantly higher thresholds for the detection of Glass patterns than controls (n=21, p=0.039) after Bonferroni correction. There was also a significant interaction between jitter level and drug-group, with polydrug-ecstasy users showing reduced sensitivity to alterations in jitter level (p=0.003). These results extend previous research, suggesting disrupted global form processing and reduced sensitivity to orientation jitter with ecstasy use. Further research is needed to investigate this finding in a larger sample of heavy ecstasy users and to differentiate the effects of other drugs. © The Author(s) 2014.

Fiber Fabry-Perot interferometer with controllable temperature sensitivity.

Science.gov (United States)

Zhang, Xinpu; Peng, Wei; Zhang, Yang

2015-12-01

We proposed a fiber taper based on the Fabry-Perot (FP) interferometer structure with controllable temperature sensitivity. The FP interferometer is formed by inserting a segment of tapered fiber tip into the capillary and subsequently splicing the other end of the capillary to a single-mode fiber (SMF), the tapered fiber endface, and the spliced face form the FP cavity. Through controlling the inserted tapered fiber length, a series of FP interferometers were made. Because the inserted taper tip has the degree of freedom along the fiber axial, when the FP interferometer is subjected to temperature variation, the thermal expansion of the fiber taper tip will resist the FP cavity length change caused by the evolution of capillary length, and we can control the temperature sensitivity by adjusting the inserted taper length. In this structure, the equivalent thermal expansion coefficient of the FP interferometer can be defined; it was used to evaluate the temperature sensitivity of the FP interferometer, which provides an effective method to eliminate the temperature effect and to enhance other measurement accuracy. We fabricated the FP interferometers and calibrated their temperature characters by measuring the wavelength shift of the resonance dips in the reflection spectrum. In a temperature range of 50°C to 150°C, the corresponding temperature sensitivities can be controlled between 0 and 1.97 pm/°C when the inserted taper is between 75 and 160 μm. Because of its controllable temperature sensitivity, ease of fabrication, and low cost, this FP interferometer can meet different temperature sensitivity requirements in various application areas, especially in the fields which need temperature insensitivity.

Sensitivity and uncertainty analyses for performance assessment modeling

International Nuclear Information System (INIS)

Doctor, P.G.

1988-08-01

Sensitivity and uncertainty analyses methods for computer models are being applied in performance assessment modeling in the geologic high level radioactive waste repository program. The models used in performance assessment tend to be complex physical/chemical models with large numbers of input variables. There are two basic approaches to sensitivity and uncertainty analyses: deterministic and statistical. The deterministic approach to sensitivity analysis involves numerical calculation or employs the adjoint form of a partial differential equation to compute partial derivatives; the uncertainty analysis is based on Taylor series expansions of the input variables propagated through the model to compute means and variances of the output variable. The statistical approach to sensitivity analysis involves a response surface approximation to the model with the sensitivity coefficients calculated from the response surface parameters; the uncertainty analysis is based on simulation. The methods each have strengths and weaknesses. 44 refs

Theorem of comparative sensitivity of fibre sensors

Science.gov (United States)

Belovolov, M. I.; Paramonov, V. M.; Belovolov, M. M.

2017-12-01

We report an analysis of sensitivity of fibre sensors of physical quantities based on different types of interferometers. We formulate and prove the following theorem: under the time-dependent external physical perturbations at nonzero frequencies (i.e., except the static and low-frequency ones) on the sensitive arms of an interferometer in the form of multiturn elements (coils), there exist such lengths L of the measuring arms of the fibre interferometers at which the sensitivity of sensors based on the Sagnac fibre interferometers can be comparable with the sensitivity of sensors based on Michelson, Mach - Zehnder, or Fabry - Perot fibre interferometers, as well as exceed it under similar other conditions (similar-type perturbations, similar arm lengths and single-mode fibre types). The consequences that follow from the theorem, important for practical implementation of arrays of fibre sensors for measurement purposes and the devices with stable metrological properties, are discussed.

Fast form alpha-2-macroglobulin

DEFF Research Database (Denmark)

Biltoft, Daniel; Gram, Jørgen Brodersen; Larsen, Anette

2017-01-01

Objectives: Investigation of the blood compatibility requires a number of sensitive assays to quantify the activation of the blood protein cascades and cells induced by biomaterials. A global assay measuring the blood compatibility of biomaterials could be a valuable tool in such regard....... In this study, we investigated whether an enzyme-linked immunosorbent assay (ELISA), that specifically measures the electrophoretic "fast form" of α2-macroglobulin (F-α2M), could be a sensitive and global marker for activation of calcium dependent and in-dependent proteases in plasma exposed to biomaterials...... in vitro. Methods: A F-α2M specific monoclonal antibody was generated and applied in an ELISA setup. Using the F-α2M ELISA, we investigated activation of calcium dependent and in-dependent proteases by polyvinylchloride (n=10), polytetrafluoroethylene (n=10) and silicone (n=10) tubings as well as glass...

Assessment and application of oats mutant forms

Energy Technology Data Exchange (ETDEWEB)

Velikovsky, V [Vyzkumny a Slechtitelsky Ustav Obilnarsky, Kromeriz (Czechoslovakia)

1978-04-01

Five oat varieties were studied for the effect of X-rays on the degree of survival, on the occurrence rate of mutations, and on the possibility of obtaining improved forms for further breeding work. Oats were treated with doses of 20,000 and 40,000 R and the latter dose was found to be highly lethal. For this reason, further studies were performed with doses of 15,000 and 25,000 R. The 'Diadem' variety (CSSR) showed the highest sensitivity to irradiation. The varieties 'Tiger' (West Germany) and 'Diane' (Belgium) showed medium susceptibility and the 'Permit' and 'Pollux' varieties (both W. Germany) were the least sensitive. In selection oriented mainly to stalk shortening and to higher resistance to lodging, the greatest number of useful macromutations was obtained from the 'Permit' variety after exposure of dry seeds to a dose of 20,000 R. The most promising mutant forms obtained in this variety were sent to some breeding stations of the Plant-Breeding and Seed-Production Enterprise Oseva for further breeding use.

Structure of the Reston ebolavirus VP30 C-terminal domain.

Science.gov (United States)

Clifton, Matthew C; Kirchdoerfer, Robert N; Atkins, Kateri; Abendroth, Jan; Raymond, Amy; Grice, Rena; Barnes, Steve; Moen, Spencer; Lorimer, Don; Edwards, Thomas E; Myler, Peter J; Saphire, Erica Ollmann

2014-04-01

The ebolaviruses can cause severe hemorrhagic fever. Essential to the ebolavirus life cycle is the protein VP30, which serves as a transcriptional cofactor. Here, the crystal structure of the C-terminal, NP-binding domain of VP30 from Reston ebolavirus is presented. Reston VP30 and Ebola VP30 both form homodimers, but the dimeric interfaces are rotated relative to each other, suggesting subtle inherent differences or flexibility in the dimeric interface.

Increasing sensitivity of MOS dosemeters in cascade connection

International Nuclear Information System (INIS)

Vychytil, F.; Cechak, T.; Gerndt, J.; Petr, I.

1978-01-01

The possibilities of increasing the sensitivity of MOS transistors in their cascade connection were studied theoretically and experimentally. The measurements confirmed the presumption that the instability of cascade-connected MOS transistors increased with the square of the number of transistors in the system. This allows systems to be formed with different sensitivity to ionizing radiation by encasing 10 to 10 4 transistors connected in cascade, which is technologically feasible. The procedure is also acceptable from the point of view of cost. (Z.M.)

HeLa Cells Containing a Truncated Form of DNA Polymerase Beta are More Sensitized to Alkylating Agents than to Agents Inducing Oxidative Stress.

Science.gov (United States)

Khanra, Kalyani; Chakraborty, Anindita; Bhattacharyya, Nandan

2015-01-01

The present study was aimed at determining the effects of alkylating and oxidative stress inducing agents on a newly identified variant of DNA polymerase beta (polβ Δ208-304) specific for ovarian cancer. Pol β Δ208-304 has a deletion of exons 11-13 which lie in the catalytic part of enzyme. We compared the effect of these chemicals on HeLa cells and HeLa cells stably transfected with this variant cloned into in pcDNAI/neo vector by MTT, colony forming and apoptosis assays. Polβ Δ208-304 cells exhibited greater sensitivity to an alkylating agent and less sensitivity towards H2O2 and UV when compared with HeLa cells alone. It has been shown that cell death in Pol β Δ208-304 transfected HeLa cells is mediated by the caspase 9 cascade. Exon 11 has nucleotidyl selection activity, while exons 12 and 13 have dNTP selection activity. Hence deletion of this part may affect polymerizing activity although single strand binding and double strand binding activity may remain same. The lack of this part may adversely affect catalytic activity of DNA polymerase beta so that the variant may act as a dominant negative mutant. This would represent clinical significance if translated into a clinical setting because resistance to radiation or chemotherapy during the relapse of the disease could be potentially overcome by this approach.

Position-sensitive X-ray detectors

International Nuclear Information System (INIS)

Hendrix, J.

1982-01-01

In this review of the application of different types of position sensitive detectors to synchrotron radiation, discussion of the proportional counters based on the gas amplification principle forms a major part. Other topics reviewed are detector requirements, multiwire proportional chamber system, drift chamber type detectors, TV detectors, and recent developments, such as that based on a micro-channel plate as the amplifying element, and charge-coupled devices. (U.K.)

Sensitivity of the Game Control of Ship in Collision Situations

Directory of Open Access Journals (Sweden)

Lisowski Józef

2015-12-01

Full Text Available The paper introduces the application of the theory of deterministic sensitivity control systems for sensitivity analysis taking place in game control systems of moving objects, such as ships. The sensitivity of parametric model of game ship control process and game control in collision situations - sensitivity to changes in its parameters have been presented. First-order and k-th order sensitivity functions of parametric model of the process and game control are described. The structure of the game ship control system in collision situations and the mathematical model of game control process in the form of state equations are given. Characteristics of sensitivity functions of the model and game ship control process on the base of computer simulation in Matlab/Simulink software have been presented. At the end are given proposals regarding the use of sensitivity analysis to practical synthesis of computer-aided system navigator in potential collision situations.

Sensitivity analysis of time-dependent laminar flows

International Nuclear Information System (INIS)

Hristova, H.; Etienne, S.; Pelletier, D.; Borggaard, J.

2004-01-01

This paper presents a general sensitivity equation method (SEM) for time dependent incompressible laminar flows. The SEM accounts for complex parameter dependence and is suitable for a wide range of problems. The formulation is verified on a problem with a closed form solution obtained by the method of manufactured solution. Systematic grid convergence studies confirm the theoretical rates of convergence in both space and time. The methodology is then applied to pulsatile flow around a square cylinder. Computations show that the flow starts with symmetrical vortex shedding followed by a transition to the traditional Von Karman street (alternate vortex shedding). Simulations show that the transition phase manifests itself earlier in the sensitivity fields than in the flow field itself. Sensitivities are then demonstrated for fast evaluation of nearby flows and uncertainty analysis. (author)

Temperature sensitive surfaces and methods of making same

Science.gov (United States)

Liang, Liang [Richland, WA; Rieke, Peter C [Pasco, WA; Alford, Kentin L [Pasco, WA

2002-09-10

Poly-n-isopropylacrylamide surface coatings demonstrate the useful property of being able to switch charateristics depending upon temperature. More specifically, these coatings switch from being hydrophilic at low temperature to hydrophobic at high temperature. Research has been conducted for many years to better characterize and control the properties of temperature sensitive coatings. The present invention provides novel temperature sensitive coatings on articles and novel methods of making temperature sensitive coatings that are disposed on the surfaces of various articles. These novel coatings contain the reaction products of n-isopropylacrylamide and are characterized by their properties such as advancing contact angles. Numerous other characteristics such as coating thickness, surface roughness, and hydrophilic-to-hydrophobic transition temperatures are also described. The present invention includes articles having temperature-sensitve coatings with improved properties as well as improved methods for forming temperature sensitive coatings.

A numerical approach to robust in-line control of roll forming processes

NARCIS (Netherlands)

Wiebenga, J.H.; Weiss, M.; Rolfe, B.; van den Boogaard, A.H.

2012-01-01

The quality of roll formed products is known to be highly sensitive and dependent on the process parameters and thus the unavoidable variations of these parameters during mass production. To maintain a constant high product quality, a new roll former with an adjustable final roll forming stand is

Spectroscopic and functional characterization of iron-sulfur cluster-bound forms of Azotobacter vinelandii (Nif)IscA.

Science.gov (United States)

Mapolelo, Daphne T; Zhang, Bo; Naik, Sunil G; Huynh, Boi Hanh; Johnson, Michael K

2012-10-16

The mechanism of [4Fe-4S] cluster assembly on A-type Fe-S cluster assembly proteins, in general, and the specific role of (Nif)IscA in the maturation of nitrogen fixation proteins are currently unknown. To address these questions, in vitro spectroscopic studies (UV-visible absorption/CD, resonance Raman and Mössbauer) have been used to investigate the mechanism of [4Fe-4S] cluster assembly on Azotobacter vinelandii(Nif)IscA, and the ability of (Nif)IscA to accept clusters from NifU and to donate clusters to the apo form of the nitrogenase Fe-protein. The results show that (Nif)IscA can rapidly and reversibly cycle between forms containing one [2Fe-2S](2+) and one [4Fe-4S](2+) cluster per homodimer via DTT-induced two-electron reductive coupling of two [2Fe-2S](2+) clusters and O(2)-induced [4Fe-4S](2+) oxidative cleavage. This unique type of cluster interconversion in response to cellular redox status and oxygen levels is likely to be important for the specific role of A-type proteins in the maturation of [4Fe-4S] cluster-containing proteins under aerobic growth or oxidative stress conditions. Only the [4Fe-4S](2+)-(Nif)IscA was competent for rapid activation of apo-nitrogenase Fe protein under anaerobic conditions. Apo-(Nif)IscA was shown to accept clusters from [4Fe-4S] cluster-bound NifU via rapid intact cluster transfer, indicating a potential role as a cluster carrier for delivery of clusters assembled on NifU. Overall the results support the proposal that A-type proteins can function as carrier proteins for clusters assembled on U-type proteins and suggest that they are likely to supply [2Fe-2S] clusters rather than [4Fe-4S] for the maturation of [4Fe-4S] cluster-containing proteins under aerobic or oxidative stress growth conditions.

Treatment of Graves' hyperthyroidism: evidence-based and emerging modalities

DEFF Research Database (Denmark)

Hegedüs, Laszlo

2009-01-01

Currently there are three well-established treatment options for hyperthyroid Graves' disease (GD): antithyroid drug therapy with thionamides (ATD), radioactive iodine treatment with (131)I, and thyroid surgery. This article reviews the current evidence so the reader can evaluate advantages...... and disadvantages of these treatment modalities. Surgery is rarely used, except for patients who have a large goiter or ophthalmopathy. Fewer than 50% of patients treated with ATD remain in long-term remission. Therefore, radioactive iodine is used increasingly. No data as yet support the routine use of biologic...

Cholestasis secondary to hyperthyroidism made worse by methimazole.

Science.gov (United States)

Majeed, Mohammed; Babu, Ambika

2006-07-01

A 28-year-old man presented with weight loss, jaundice, and pruritus. This was diagnosed to be secondary to Graves disease and the patient was prescribed methimazole. He returned 2 weeks later with worsening of his jaundice. Further investigation, including liver biopsy, indicated that there was superimposed methimazole-induced cholestasis. Discontinuation of methimazole and treatment of hyperthyroidism with lithium followed by radioactive iodine therapy resulted in resolution of his symptoms. This case highlights the fact that worsening cholestasis after therapy for Graves disease should raise the possibility of thionamide-induced exaggeration of liver cholestasis.

Light-sensitive brain pathways and aging.

Science.gov (United States)

Daneault, V; Dumont, M; Massé, É; Vandewalle, G; Carrier, J

2016-03-15

Notwithstanding its effects on the classical visual system allowing image formation, light acts upon several non-image-forming (NIF) functions including body temperature, hormonal secretions, sleep-wake cycle, alertness, and cognitive performance. Studies have shown that NIF functions are maximally sensitive to blue wavelengths (460-480 nm), in comparison to longer light wavelengths. Higher blue light sensitivity has been reported for melatonin suppression, pupillary constriction, vigilance, and performance improvement but also for modulation of cognitive brain functions. Studies investigating acute stimulating effects of light on brain activity during the execution of cognitive tasks have suggested that brain activations progress from subcortical regions involved in alertness, such as the thalamus, the hypothalamus, and the brainstem, before reaching cortical regions associated with the ongoing task. In the course of aging, lower blue light sensitivity of some NIF functions has been reported. Here, we first describe neural pathways underlying effects of light on NIF functions and we discuss eye and cerebral mechanisms associated with aging which may affect NIF light sensitivity. Thereafter, we report results of investigations on pupillary constriction and cognitive brain sensitivity to light in the course of aging. Whereas the impact of light on cognitive brain responses appears to decrease substantially, pupillary constriction seems to remain more intact over the lifespan. Altogether, these results demonstrate that aging research should take into account the diversity of the pathways underlying the effects of light on specific NIF functions which may explain their differences in light sensitivity.

Highly sensitive microcalorimeters for radiation research

International Nuclear Information System (INIS)

Avaev, V.N.; Demchuk, B.N.; Ioffe, L.A.; Efimov, E.P.

1984-01-01

Calorimetry is used in research at various types of nuclear-physics installations to obtain information on the quantitative and qualitative composition of ionizing radiation in a reactor core and in the surrounding layers of the biological shield. In this paper, the authors examine the characteristics of highly sensitive microcalorimeters with modular semiconductor heat pickups designed for operation in reactor channels. The microcalorimeters have a thin-walled aluminum housing on whose inner surface modular heat pickups are placed radially as shown here. The results of measurements of the temperature dependence of the sensitivity of the microcalorimeters are shown. The results of measuring the sensitivity of a PMK-2 microcalorimeter assembly as a function of integrated neutron flux for three energy intervals and the adsorbed gamma energy are shown. In order to study specimens with different shapes and sizes, microcalorimeters with chambers in the form of cylinders and a parallelepiped were built and tested

Postclosure risks of alternative SRP nuclear waste forms in geologic repositories

International Nuclear Information System (INIS)

Cheung, H.; Edwards, L.; Harvey, T.; Revelli, M.

1982-05-01

The postclosure risk of REFERENCE and ALTERNATIVE waste forms for the defense high-level waste at the Savannah River Plant (SRP) were compared by analyses with a computer code, MISER, written to study the effects of repository features in a probabilistic framework. MISER traces radionuclide flows through a network of stream tubes from the repository to risk-sensitive points. Uncertainties in waste form, package properties, and geotechnical data are accounted for with Monte Carlo techniques. Our results show: (1) for generic layered-salt and basalt repositories, the difference in performance between the two waste forms is insignificant; (2) where the doses are sensitive to uncertainties in leaching rates, the doses are orders of magnitude below background; (3) disruptive events contribute only slightly to the risk of a layered-salt repository; (4) simple design alterations have strong effects on near field doses; (5) great care should be exercised in selecting the location at which repository risks are to be measured, calculated, or regulated

N-glycosylation and disulfide bonding affects GPRC6A receptor expression, function, and dimerization

DEFF Research Database (Denmark)

Nørskov-Lauritsen, Lenea; Jørgensen, Stine; Bräuner-Osborne, Hans

2015-01-01

Investigation of post-translational modifications of receptor proteins is important for our understanding of receptor pharmacology and disease physiology. However, our knowledge about post-translational modifications of class C G protein-coupled receptors and how these modifications regulate expr...... covalently linked dimers through cysteine disulfide linkage in the extracellular amino-terminal domain and here we show that GPRC6A indeed is a homodimer and that a disulfide bridge between the C131 residues is formed....

An ancient form of position-sensitive detector - the individual counter array

International Nuclear Information System (INIS)

Hewat, A.W.

1983-01-01

Large position sensitive detectors (PSDs) have been very successful as high efficiency neutron powder diffractometers. Complete powder patterns can be obtained within minutes, making possible real-time measurements of structural changes accompanying chemical and electrochemical reactions. The angular resolution of such machines is determined by the diameter of the sample, and not simply by the resolution of the detector itself. It is argued that since sample diameters are usually 5mm to 10mm, it is possible to use an array of individual counters of similar diameter rather than a true PSD. Such a low to medium resolution individual counter array (ICA) can be made more efficient than the true PSD, produces an identical diffraction pattern, and has several practical advantages, including covering a greater solid angle. For high resolution powder diffraction, it has already been demonstrated that an ICA, in this case associated with Soller collimators, is again the most efficient solution. This is because the sample volume (and intensity) of a high resolution PSD decreases quadratically with the diameter of the sample. The only alternative to very small samples would be a large sample-detector distance, and then large vertical divergences cannot be achieved because of mechanical limitations on gas-filled PSD apertures; again intensity is lost. The resolution and efficiency of the ICA are discussed. (author)

Shape-forming and densification of ceramic superconductors

International Nuclear Information System (INIS)

Prakash, Om; Thomas, C.A.; Magadum, A.P.; Anklekar, R.M.; Khosla, N.K.; Kumar, Sunil; Chaudhuri, B.; Ramesh, M.; Rao, B.T.; Rama Mohan, T.R.

1991-01-01

Processing studies on varied shape-forming and densification of bulk ceramic superconductor, YBa 2 Cu 3 Osub(7-δ), are reported in this paper. Polyvinyl butyral-polyethylene glycol-trichloroethylene has been found to be the best binder-plasticizer-solvent system in plastic shape-forming. The effect of initial particle morphology on final densification has been the most sensitive single parameter as compared to compaction pressure and final sintering durations at ∼930degC. 1-2-3 powders of mean particle size ∼1.94μm have yielded sintered densities ∼92%T.D. albeit with lower oxygen intake Osub(6.7). (author). 8 refs., 8 figs

Sensitivity profiles calculated with the UNISENS system

International Nuclear Information System (INIS)

Claro, L.H.; Menezes, A.

1985-01-01

Sensitivity profiles of the multiplication factor and several central reaction ratios for benchmarks ZPR 6/7, ZPR 3/11, FLATTOP-25, GODIVA and BIG-TEN, are presented in grafic form. A possible utilization is showed throught some modification to the ENDF/B-IV data file proposed for version ENDF/B-V. (Author) [pt

Computational modeling of the bHLH domain of the transcription factor TWIST1 and R118C, S144R and K145E mutants

Directory of Open Access Journals (Sweden)

Maia Amanda M

2012-07-01

Full Text Available Abstract Background Human TWIST1 is a highly conserved member of the regulatory basic helix-loop-helix (bHLH transcription factors. TWIST1 forms homo- or heterodimers with E-box proteins, such as E2A (isoforms E12 and E47, MYOD and HAND2. Haploinsufficiency germ-line mutations of the twist1 gene in humans are the main cause of Saethre-Chotzen syndrome (SCS, which is characterized by limb abnormalities and premature fusion of cranial sutures. Because of the importance of TWIST1 in the regulation of embryonic development and its relationship with SCS, along with the lack of an experimentally solved 3D structure, we performed comparative modeling for the TWIST1 bHLH region arranged into wild-type homodimers and heterodimers with E47. In addition, three mutations that promote DNA binding failure (R118C, S144R and K145E were studied on the TWIST1 monomer. We also explored the behavior of the mutant forms in aqueous solution using molecular dynamics (MD simulations, focusing on the structural changes of the wild-type versus mutant dimers. Results The solvent-accessible surface area of the homodimers was smaller on wild-type dimers, which indicates that the cleft between the monomers remained more open on the mutant homodimers. RMSD and RMSF analyses indicated that mutated dimers presented values that were higher than those for the wild-type dimers. For a more careful investigation, the monomer was subdivided into four regions: basic, helix I, loop and helix II. The basic domain presented a higher flexibility in all of the parameters that were analyzed, and the mutant dimer basic domains presented values that were higher than the wild-type dimers. The essential dynamic analysis also indicated a higher collective motion for the basic domain. Conclusions Our results suggest the mutations studied turned the dimers into more unstable structures with a wider cleft, which may be a reason for the loss of DNA binding capacity observed for in vitro

Scenario sensitivity analyses performed on the PRESTO-EPA LLW risk assessment models

International Nuclear Information System (INIS)

Bandrowski, M.S.

1988-01-01

The US Environmental Protection Agency (EPA) is currently developing standards for the land disposal of low-level radioactive waste. As part of the standard development, EPA has performed risk assessments using the PRESTO-EPA codes. A program of sensitivity analysis was conducted on the PRESTO-EPA codes, consisting of single parameter sensitivity analysis and scenario sensitivity analysis. The results of the single parameter sensitivity analysis were discussed at the 1987 DOE LLW Management Conference. Specific scenario sensitivity analyses have been completed and evaluated. Scenario assumptions that were analyzed include: site location, disposal method, form of waste, waste volume, analysis time horizon, critical radionuclides, use of buffer zones, and global health effects

Chemical crosslinking of acrylic acid to form biocompatible pH sensitive hydrogel reinforced with cellulose nanocrystals (CNC)

International Nuclear Information System (INIS)

Lim, Lim Sze; Ahmad, Ishak; Lazim, Mohd Azwani Shah Mat; Amin, Mohd. Cairul Iqbal Mohd

2014-01-01

The purpose of this study is to produce a novel pH and temperature sensitive hydrogel, composed of poly(acrylic acid) (PAA) and cellulose nanocrystal (CNC). CNC was extracted from kenaf fiber through a series of alkali and bleaching treatments followed by acid hydrolysis. The PAA was then subjected to chemical cross-linking using the cross-linking agent (N,N-methylenebisacrylamide) with CNC entrapped in PAA matrix. The mixture was casted onto petri dish to obtain disc shape hydrogel. The effects of reaction conditions such as the ratio of PAA and CNC on the swelling behavior of the hydrogel obtained towards pH and temperature were studied. The obtained hydrogel was further subjected to different tests such swelling test for swelling behaviour at different pH and temperature along with scanning electron microscopy (SEM) for morphology analysis. The hydrogel obtained showed excellent pH sensitivity and obtained maximum swelling at pH 7. Besides that, hydrogel obtained showed significant increase in swelling ratio when temperature of swelling medium was increased from 25°C to 37°C. SEM micrograph showed that the pore size of the hydrogel decreases with increase of CNC content proving that the hydrogel structure became more rigid with addition of CNC. The PAA/CNC hydrogel with such excellent sensitivity towards pH and temperature can be developed further as drug carrier

Chemical crosslinking of acrylic acid to form biocompatible pH sensitive hydrogel reinforced with cellulose nanocrystals (CNC)

Energy Technology Data Exchange (ETDEWEB)

Lim, Lim Sze; Ahmad, Ishak; Lazim, Mohd Azwani Shah Mat [Faculty of Science and Technology, University Kebangsaan Malaysia, 43600 UKM, Bangi, Selangor (Malaysia); Amin, Mohd. Cairul Iqbal Mohd [Faculty of Pharmacy, University Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur (Malaysia)

2014-09-03

The purpose of this study is to produce a novel pH and temperature sensitive hydrogel, composed of poly(acrylic acid) (PAA) and cellulose nanocrystal (CNC). CNC was extracted from kenaf fiber through a series of alkali and bleaching treatments followed by acid hydrolysis. The PAA was then subjected to chemical cross-linking using the cross-linking agent (N,N-methylenebisacrylamide) with CNC entrapped in PAA matrix. The mixture was casted onto petri dish to obtain disc shape hydrogel. The effects of reaction conditions such as the ratio of PAA and CNC on the swelling behavior of the hydrogel obtained towards pH and temperature were studied. The obtained hydrogel was further subjected to different tests such swelling test for swelling behaviour at different pH and temperature along with scanning electron microscopy (SEM) for morphology analysis. The hydrogel obtained showed excellent pH sensitivity and obtained maximum swelling at pH 7. Besides that, hydrogel obtained showed significant increase in swelling ratio when temperature of swelling medium was increased from 25°C to 37°C. SEM micrograph showed that the pore size of the hydrogel decreases with increase of CNC content proving that the hydrogel structure became more rigid with addition of CNC. The PAA/CNC hydrogel with such excellent sensitivity towards pH and temperature can be developed further as drug carrier.

iFORM: Incorporating Find Occurrence of Regulatory Motifs.

Science.gov (United States)

Ren, Chao; Chen, Hebing; Yang, Bite; Liu, Feng; Ouyang, Zhangyi; Bo, Xiaochen; Shu, Wenjie

2016-01-01

Accurately identifying the binding sites of transcription factors (TFs) is crucial to understanding the mechanisms of transcriptional regulation and human disease. We present incorporating Find Occurrence of Regulatory Motifs (iFORM), an easy-to-use and efficient tool for scanning DNA sequences with TF motifs described as position weight matrices (PWMs). Both performance assessment with a receiver operating characteristic (ROC) curve and a correlation-based approach demonstrated that iFORM achieves higher accuracy and sensitivity by integrating five classical motif discovery programs using Fisher's combined probability test. We have used iFORM to provide accurate results on a variety of data in the ENCODE Project and the NIH Roadmap Epigenomics Project, and the tool has demonstrated its utility in further elucidating individual roles of functional elements. Both the source and binary codes for iFORM can be freely accessed at https://github.com/wenjiegroup/iFORM. The identified TF binding sites across human cell and tissue types using iFORM have been deposited in the Gene Expression Omnibus under the accession ID GSE53962.

Environment sensitive cracking in light water reactor pressure boundary materials

International Nuclear Information System (INIS)

Haenninen, H.; Aho-Mantila, I.

1985-01-01

The purpose of the paper is to review the available methods and the most promising future possibilities of preventive maintenance to counteract the various forms of environment sensitive cracking of pressure boundary materials in light water reactors. Environment sensitive cracking is considered from the metallurgical, mechanical and environmental point of view. The main emphasis is on intergranular stress corrosion cracking of austenitic stainless steels and high strenght Ni-base alloys, as well as on corrosion fatigue of low alloy and stainless steels. Finally, some general ideas how to predict, reduce or eliminate environment sensitive cracking in service are presented

Sensitization to allergens of domestic animals

Directory of Open Access Journals (Sweden)

A. N. Pampura

2018-01-01

Full Text Available At present, sensitization to airborne allergens in domestic animals is absolutely rightly considered one of the key risk factors for the development of allergic rhinitis and bronchial asthma, as well as largely determines the development of severe forms of atopic dermatitis and respiratory allergosis. Of particularimportance isthe fact that, unlike othertriggers, the elimination of allergensin domestic animals is often associated with internal resistance from patients. The article presents the current data on the prevalence of sensitization, the properties and clinical significance of the main allergens of cats and dogs, outlines approaches to conducting elimination activities.

Role of α and β Transmembrane Domains in Integrin Clustering

Directory of Open Access Journals (Sweden)

Amir Shamloo

2015-11-01

Full Text Available Integrins are transmembrane proteins playing a crucial role in the mechanical signal transduction from the outside to the inside of a cell, and vice versa. Nevertheless, this signal transduction could not be implemented by a single protein. Rather, in order for integrins to be able to participate in signal transduction, they need to be activated and produce clusters first. As integrins consist of α- and β-subunits that are separate in the active state, studying both subunits separately is of a great importance, for, in the active state, the distance between α- and β-subunits is long enough that they do not influence one another significantly. Thus, this study aims to investigate the tendency of transmembrane domains of integrins to form homodimers. We used both Steered and MARTINI Coarse-grained molecular dynamics method to perform our simulations, mainly because of a better resolution and computational feasibility that each of these methods could provide to us. Using the Steered molecular dynamics method for α- and β-subunits, we found that the localized lipid packing prevented them from clustering. Nonetheless, the lipid packing phenomenon was found to be an artifact after investigating this process using a coarse grained (CG model. Exploiting the coarse-grained molecular dynamics simulations, we found that α- and β-subunits tend to form a stable homo-dimer.

Antithyroid drugs induced agranulocytosis and multiple myeloma: case report and general considerations.

Science.gov (United States)

Dănciulescu Miulescu, R; Carşote, M; Trifănescu, R; Ferechide, D; Poiană, C

2013-09-15

Antithyroid drugs as thionamides are largely used in the treatment of the thyrotoxicosis. Side effects were reported in less than 10% of the cases, especially hematological, hepatic or skin allergies. One of the most severe manifestations is agranulocytosis, probably based on an immune mechanism that is exacerbated by the presence of the thyroid autoimmune disease itself. If the presence of the severe leucopenia is actually an epiphenomenon of a preexisting hematological disturbance as multiple myeloma is debated. The myeloma may also be correlated with an autoimmune predisposition. We present the case of a 56 years old female patient diagnosed with Graves' disease, who developed agranulocytosis after 8 months of therapy with thiamazole. Two months after antithyroid drug's withdrawal, the granulocytes number increased and she received therapy with radioiodine. Two years later she came back for diffuse bone pain that turned out to be caused by a multiple myeloma, confirmed by bone marrow biopsy. It might be a connection between the severe form of leucopenia that the patient developed and the medullar malignancy.

Sensitivity-Bandwidth Limit in a Multimode Optoelectromechanical Transducer

Science.gov (United States)

Moaddel Haghighi, I.; Malossi, N.; Natali, R.; Di Giuseppe, G.; Vitali, D.

2018-03-01

An optoelectromechanical system formed by a nanomembrane capacitively coupled to an L C resonator and to an optical interferometer has recently been employed for the highly sensitive optical readout of rf signals [T. Bagci et al., Nature (London) 507, 81 (2013), 10.1038/nature13029]. We propose and experimentally demonstrate how the bandwidth of such a transducer can be increased by controlling the interference between two electromechanical interaction pathways of a two-mode mechanical system. With a proof-of-principle device operating at room temperature, we achieve a sensitivity of 300 nV /√{Hz } over a bandwidth of 15 kHz in the presence of radio-frequency noise, and an optimal shot-noise-limited sensitivity of 10 nV /√{Hz } over a bandwidth of 5 kHz. We discuss strategies for improving the performance of the device, showing that, for the same given sensitivity, a mechanical multimode transducer can achieve a bandwidth significantly larger than that for a single-mode one.

Forming limit curves of DP600 determined in high-speed Nakajima tests and predicted by two different strain-rate-sensitive models

Science.gov (United States)

Weiß-Borkowski, Nathalie; Lian, Junhe; Camberg, Alan; Tröster, Thomas; Münstermann, Sebastian; Bleck, Wolfgang; Gese, Helmut; Richter, Helmut

2018-05-01

Determination of forming limit curves (FLC) to describe the multi-axial forming behaviour is possible via either experimental measurements or theoretical calculations. In case of theoretical determination, different models are available and some of them consider the influence of strain rate in the quasi-static and dynamic strain rate regime. Consideration of the strain rate effect is necessary as many material characteristics such as yield strength and failure strain are affected by loading speed. In addition, the start of instability and necking depends not only on the strain hardening coefficient but also on the strain rate sensitivity parameter. Therefore, the strain rate dependency of materials for both plasticity and the failure behaviour is taken into account in crash simulations for strain rates up to 1000 s-1 and FLC can be used for the description of the material's instability behaviour at multi-axial loading. In this context, due to the strain rate dependency of the material behaviour, an extrapolation of the quasi-static FLC to dynamic loading condition is not reliable. Therefore, experimental high-speed Nakajima tests or theoretical models shall be used to determine the FLC at high strain rates. In this study, two theoretical models for determination of FLC at high strain rates and results of experimental high-speed Nakajima tests for a DP600 are presented. One of the theoretical models is the numerical algorithm CRACH as part of the modular material and failure model MF GenYld+CrachFEM 4.2, which is based on an initial imperfection. Furthermore, the extended modified maximum force criterion considering the strain rate effect is also used to predict the FLC. These two models are calibrated by the quasi-static and dynamic uniaxial tensile tests and bulge tests. The predictions for the quasi-static and dynamic FLC by both models are presented and compared with the experimental results.

The Specificity of Innate Immune Responses Is Enforced by Repression of Interferon Response Elements by NF-κB p50

Science.gov (United States)

Cheng, Christine S.; Feldman, Kristyn E.; Lee, James; Verma, Shilpi; Huang, De-Bin; Huynh, Kim; Chang, Mikyoung; Ponomarenko, Julia V.; Sun, Shao-Cong; Benedict, Chris A.; Ghosh, Gourisankar; Hoffmann, Alexander

2011-01-01

The specific binding of transcription factors to cognate sequence elements is thought to be critical for the generation of specific gene expression programs. Members of the nuclear factor κB (NF-κB) and interferon (IFN) regulatory factor (IRF) transcription factor families bind to the κB site and the IFN response element (IRE), respectively, of target genes, and they are activated in macrophages after exposure to pathogens. However, how these factors produce pathogen-specific inflammatory and immune responses remains poorly understood. Combining top-down and bottom-up systems biology approaches, we have identified the NF-κB p50 homodimer as a regulator of IRF responses. Unbiased genome-wide expression and biochemical and structural analyses revealed that the p50 homodimer repressed a subset of IFN-inducible genes through a previously uncharacterized subclass of guanine-rich IRE (G-IRE) sequences. Mathematical modeling predicted that the p50 homodimer might enforce the stimulus specificity of composite promoters. Indeed, the production of the antiviral regulator IFN-β was rendered stimulus-specific by the binding of the p50 homodimer to the G-IRE–containing IFNβ enhancer to suppress cytotoxic IFN signaling. Specifically, a deficiency in p50 resulted in the inappropriate production of IFN-β in response to bacterial DNA sensed by Toll-like receptor 9. This role for the NF-κB p50 homodimer in enforcing the specificity of the cellular response to pathogens by binding to a subset of IRE sequences alters our understanding of how the NF-κB and IRF signaling systems cooperate to regulate antimicrobial immunity. PMID:21343618

TL sensitivity of CaSO4:Dy phosphor powder - effect of grinding

International Nuclear Information System (INIS)

Shastry, S.S.; Kher, R.K.

1979-01-01

Grinding of polycrystalline CaSO 4 :Dy phosphor to powder form induces lattice defects. Changes in thermoluminescence (TL) sensitivity due to variation in trap density in the bulk and on the surface of phosphor grains are studied using gamma and UV radiations. TL sensitivity to gamma increases with grinding time due to the contribution from the new bulk traps which are generated by grinding. The surface traps degrade with increase in grinding time resulting in a decrease in UV sensitivity. Results on regeneration of the TL sensitivity due to annealing at different temperatures are also included. (Auth.)

Radiation-sensitive compounds and methods of using same

International Nuclear Information System (INIS)

DeMajistre, R.

1977-01-01

Novel diacrylates are prepared by reacting a monohydroxylated acrylic monomer with a polyisocyanate. The reaction product may be polymerized by subjecting to ionizing irradiation, actinic light or to free radical catalysis to form a useful coating material. The diacrylates may also be copolymerized with other radiation sensitive materials

Generalized tolerance sensitivity and DEA metric sensitivity

OpenAIRE

Neralić, Luka; E. Wendell, Richard

2015-01-01

This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA). Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

Generalized tolerance sensitivity and DEA metric sensitivity

Directory of Open Access Journals (Sweden)

Luka Neralić

2015-03-01

Full Text Available This paper considers the relationship between Tolerance sensitivity analysis in optimization and metric sensitivity analysis in Data Envelopment Analysis (DEA. Herein, we extend the results on the generalized Tolerance framework proposed by Wendell and Chen and show how this framework includes DEA metric sensitivity as a special case. Further, we note how recent results in Tolerance sensitivity suggest some possible extensions of the results in DEA metric sensitivity.

Objectively combining AR5 instrumental period and paleoclimate climate sensitivity evidence

Science.gov (United States)

Lewis, Nicholas; Grünwald, Peter

2018-03-01

Combining instrumental period evidence regarding equilibrium climate sensitivity with largely independent paleoclimate proxy evidence should enable a more constrained sensitivity estimate to be obtained. Previous, subjective Bayesian approaches involved selection of a prior probability distribution reflecting the investigators' beliefs about climate sensitivity. Here a recently developed approach employing two different statistical methods—objective Bayesian and frequentist likelihood-ratio—is used to combine instrumental period and paleoclimate evidence based on data presented and assessments made in the IPCC Fifth Assessment Report. Probabilistic estimates from each source of evidence are represented by posterior probability density functions (PDFs) of physically-appropriate form that can be uniquely factored into a likelihood function and a noninformative prior distribution. The three-parameter form is shown accurately to fit a wide range of estimated climate sensitivity PDFs. The likelihood functions relating to the probabilistic estimates from the two sources are multiplicatively combined and a prior is derived that is noninformative for inference from the combined evidence. A posterior PDF that incorporates the evidence from both sources is produced using a single-step approach, which avoids the order-dependency that would arise if Bayesian updating were used. Results are compared with an alternative approach using the frequentist signed root likelihood ratio method. Results from these two methods are effectively identical, and provide a 5-95% range for climate sensitivity of 1.1-4.05 K (median 1.87 K).

Crystal structure of a human single domain antibody dimer formed through V(H-V(H non-covalent interactions.

Directory of Open Access Journals (Sweden)

Toya Nath Baral

Full Text Available Single-domain antibodies (sdAbs derived from human V(H are considered to be less soluble and prone to aggregate which makes it difficult to determine the crystal structures. In this study, we isolated and characterized two anti-human epidermal growth factor receptor-2 (HER2 sdAbs, Gr3 and Gr6, from a synthetic human V(H phage display library. Size exclusion chromatography and surface plasmon resonance analyses demonstrated that Gr3 is a monomer, but that Gr6 is a strict dimer. To understand this different molecular behavior, we solved the crystal structure of Gr6 to 1.6 Å resolution. The crystal structure revealed that the homodimer assembly of Gr6 closely mimics the V(H-V(L heterodimer of immunoglobulin variable domains and the dimerization interface is dominated by hydrophobic interactions.

Protein associations in DnaA-ATP hydrolysis mediated by the Hda-replicase clamp complex.

Science.gov (United States)

Su'etsugu, Masayuki; Shimuta, Toh-Ru; Ishida, Takuma; Kawakami, Hironori; Katayama, Tsutomu

2005-02-25

In Escherichia coli, the activity of ATP-bound DnaA protein in initiating chromosomal replication is negatively controlled in a replication-coordinated manner. The RIDA (regulatory inactivation of DnaA) system promotes DnaA-ATP hydrolysis to produce the inactivated form DnaA-ADP in a manner depending on the Hda protein and the DNA-loaded form of the beta-sliding clamp, a subunit of the replicase holoenzyme. A highly functional form of Hda was purified and shown to form a homodimer in solution, and two Hda dimers were found to associate with a single clamp molecule. Purified mutant Hda proteins were used in a staged in vitro RIDA system followed by a pull-down assay to show that Hda-clamp binding is a prerequisite for DnaA-ATP hydrolysis and that binding is mediated by an Hda N-terminal motif. Arg(168) in the AAA(+) Box VII motif of Hda plays a role in stable homodimer formation and in DnaA-ATP hydrolysis, but not in clamp binding. Furthermore, the DnaA N-terminal domain is required for the functional interaction of DnaA with the Hda-clamp complex. Single cells contain approximately 50 Hda dimers, consistent with the results of in vitro experiments. These findings and the features of AAA(+) proteins, including DnaA, suggest the following model. DnaA-ATP is hydrolyzed at a binding interface between the AAA(+) domains of DnaA and Hda; the DnaA N-terminal domain supports this interaction; and the interaction of DnaA-ATP with the Hda-clamp complex occurs in a catalytic mode.

Sensitivity of system stability to model structure

Science.gov (United States)

Hosack, G.R.; Li, H.W.; Rossignol, P.A.

2009-01-01

A community is stable, and resilient, if the levels of all community variables can return to the original steady state following a perturbation. The stability properties of a community depend on its structure, which is the network of direct effects (interactions) among the variables within the community. These direct effects form feedback cycles (loops) that determine community stability. Although feedback cycles have an intuitive interpretation, identifying how they form the feedback properties of a particular community can be intractable. Furthermore, determining the role that any specific direct effect plays in the stability of a system is even more daunting. Such information, however, would identify important direct effects for targeted experimental and management manipulation even in complex communities for which quantitative information is lacking. We therefore provide a method that determines the sensitivity of community stability to model structure, and identifies the relative role of particular direct effects, indirect effects, and feedback cycles in determining stability. Structural sensitivities summarize the degree to which each direct effect contributes to stabilizing feedback or destabilizing feedback or both. Structural sensitivities prove useful in identifying ecologically important feedback cycles within the community structure and for detecting direct effects that have strong, or weak, influences on community stability. The approach may guide the development of management intervention and research design. We demonstrate its value with two theoretical models and two empirical examples of different levels of complexity. ?? 2009 Elsevier B.V. All rights reserved.

Method of forming electronically conducting polymers on conducting and nonconducting substrates

Science.gov (United States)

Murphy, Oliver J. (Inventor); Hitchens, G. Duncan (Inventor); Hodko, Dalibor (Inventor); Clarke, Eric T. (Inventor); Miller, David L. (Inventor); Parker, Donald L. (Inventor)

2001-01-01

The present invention provides electronically conducting polymer films formed from photosensitive formulations of pyrrole and an electron acceptor that have been selectively exposed to UV light, laser light, or electron beams. The formulations may include photoinitiators, flexibilizers, solvents and the like. These solutions can be used in applications including printed circuit boards and through-hole plating and enable direct metallization processes on non-conducting substrates. After forming the conductive polymer patterns, a printed wiring board can be formed by sensitizing the polymer with palladium and electrolytically depositing copper.

Reward sensitivity and food addiction in women.

Science.gov (United States)

Loxton, Natalie J; Tipman, Renée J

2017-08-01

Sensitivity to the rewarding properties of appetitive substances has long been implicated in excessive consumption of palatable foods and drugs of abuse. Previous research focusing on individual differences in reward responsiveness has found heightened trait reward sensitivity to be associated with binge-eating, hazardous drinking, and illicit substance use. Food addiction has been proposed as an extreme form of compulsive-overeating and has been associated with genetic markers of heightened reward responsiveness. However, little research has explicitly examined the association between reward sensitivity and food addiction. Further, the processes by which individual differences in this trait are associated with excessive over-consumption has not been determined. A total of 374 women from the community completed an online questionnaire assessing reward sensitivity, food addiction, emotional, externally-driven, and hedonic eating. High reward sensitivity was significantly associated with greater food addiction symptoms (r = 0.31). Bootstrapped tests of indirect effects found the relationship between reward sensitivity and food addiction symptom count to be uniquely mediated by binge-eating, emotional eating, and hedonic eating (notably, food availability). These indirect effects held even when controlling for BMI, anxiety, depression, and trait impulsivity. This study further supports the argument that high levels of reward sensitivity may offer a trait marker of vulnerability to excessive over-eating, beyond negative affect and impulse-control deficits. That the hedonic properties of food (especially food availability), emotional, and binge-eating behavior act as unique mediators suggest that interventions for reward-sensitive women presenting with food addiction may benefit from targeting food availability in addition to management of negative affect. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sensitivity analysis of reactive ecological dynamics.

Science.gov (United States)

Verdy, Ariane; Caswell, Hal

2008-08-01

Ecological systems with asymptotically stable equilibria may exhibit significant transient dynamics following perturbations. In some cases, these transient dynamics include the possibility of excursions away from the equilibrium before the eventual return; systems that exhibit such amplification of perturbations are called reactive. Reactivity is a common property of ecological systems, and the amplification can be large and long-lasting. The transient response of a reactive ecosystem depends on the parameters of the underlying model. To investigate this dependence, we develop sensitivity analyses for indices of transient dynamics (reactivity, the amplification envelope, and the optimal perturbation) in both continuous- and discrete-time models written in matrix form. The sensitivity calculations require expressions, some of them new, for the derivatives of equilibria, eigenvalues, singular values, and singular vectors, obtained using matrix calculus. Sensitivity analysis provides a quantitative framework for investigating the mechanisms leading to transient growth. We apply the methodology to a predator-prey model and a size-structured food web model. The results suggest predator-driven and prey-driven mechanisms for transient amplification resulting from multispecies interactions.

Evaluating Urban Forms for Comparison Studies in the Massing Design Stage

Directory of Open Access Journals (Sweden)

Kian Wee Chen

2017-06-01

Full Text Available We introduce five performance indicators to facilitate the comparison of urban massing design in the early design stages. The five simple indicators are based on existing studies and cover three main performance areas that are sensitive to urban form changes: solar, ventilation, and connectivity potentials. The first three indicators—the non-solar heated façade to floor area index, daylight façade to floor area index, and photovoltaics envelope to floor area index—measure the solar potential. The frontal area index measures the ventilation potential and the route-directness index measures the connectivity potential. The indicators are simple to use, as they only require urban geometry data for their calculation. We demonstrate the indicators in two case studies; variations in the values of these indicators show that they are sensitive to urban form changes and can be used in comparative studies to identify better performing urban forms among massing designs. We implement the indicators as an open-source Python library, Pyliburo, that designers and researchers can readily access and integrate into their existing design workflows.

High-throughput spectrometer designs in a compact form-factor: principles and applications

Science.gov (United States)

Norton, S. M.

2013-05-01

Many compact, portable Raman spectrometers have entered the market in the past few years with applications in narcotics and hazardous material identification, as well as verification applications in pharmaceuticals and security screening. Often, the required compact form-factor has forced designers to sacrifice throughput and sensitivity for portability and low-cost. We will show that a volume phase holographic (VPH)-based spectrometer design can achieve superior throughput and thus sensitivity over conventional Czerny-Turner reflective designs. We will look in depth at the factors influencing throughput and sensitivity and illustrate specific VPH-based spectrometer examples that highlight these design principles.

Prediction of Gas Leak Tightness of Superplastically Formed Products

NARCIS (Netherlands)

Snippe, Q.H.C.; Meinders, Vincent T.; Barlat, F; Moon, Y.H.; Lee, M.G.

2010-01-01

In some applications, in this case an aluminium box in a subatomic particle detector containing highly sensitive detecting devices, it is important that a formed sheet should show no gas leak from one side to the other. In order to prevent a trial-and-error procedure to make this leak tight box, a

Radiation polymerized hot melt pressure sensitive adhesives

International Nuclear Information System (INIS)

Pastor, S.D.; Skoultchi, M.M.

1977-01-01

Hot melt pressure sensitive adhesive compositions formed by copolymerizing at least one 3-(chlorinated aryloxy)-2-hydroxypropyl ester of an alpha, beta unsaturated carboxylic acid with acrylate based copolymerizable monomers, are described. The resultant ethylenically saturated prepolymer is heated to a temperature sufficient to render it fluid and flowable. This composition is coated onto a substrate and exposed to ultraviolet radiation

Carbon coated stainless steel as counter electrode for dye sensitized solar cells

Science.gov (United States)

Prakash, Shejale Kiran; Sharma, Rakesh K.; Roy, Mahesh S.; Kumar, Mahesh

2014-10-01

A new type of counter electrode for dye sensitized solar cells has been fabricated using a stainless steel sheet as substrate and graphite, graphene and multiwall carbon nanotubes as the catalytic material which applied by screen printing technique. The sheet resistances of the substrates and there influence on the dye sensitized solar cells has been studied. The fabricated counter electrodes i.e. SS-graphite, SS-graphene SS-MWCNT and SS-platinum were tested for their photovoltaic response in the form of dye sensitized solar cells.

X-ray diffraction study of choline chloride's β form

International Nuclear Information System (INIS)

Petrouleas, V.; Lemmon, R.M.; Christensen, A.

1978-01-01

The organic salt choline chloride exists in two crystalline polymorphs. One (the α form) is extraordinarily sensitive to ionizing radiation, the other (the β form) is not. The present report describes an x-ray diffraction study of the β form. The structure has been found to be highly disordered face centered cubic. A reasonable least-square refinement of the intensity data has been achieved in the centrosymmetric space group Fm3 or Fm3m by use of a molecular model with restrained bond lengths. The results show that in the β form the electronic density due to the choline cation is closely spaced around the N, so that hydrogen bonding to the chloride is unlikely. Comparison with infrared and NMR data indicates that the disordering is dynamic and can be ascribed to rotations of the choline ion around crystallographic symmetry axes. Possible connections of these results with the radiation stability of the β form are discussed

Brief exposure to sensory cues elicits stimulus-nonspecific general sensitization in an insect.

Directory of Open Access Journals (Sweden)

Sebastian Minoli

Full Text Available The effect of repeated exposure to sensory stimuli, with or without reward is well known to induce stimulus-specific modifications of behaviour, described as different forms of learning. In recent studies we showed that a brief single pre-exposure to the female-produced sex pheromone or even a predator sound can increase the behavioural and central nervous responses to this pheromone in males of the noctuid moth Spodoptera littoralis. To investigate if this increase in sensitivity might be restricted to the pheromone system or is a form of general sensitization, we studied here if a brief pre-exposure to stimuli of different modalities can reciprocally change behavioural and physiological responses to olfactory and gustatory stimuli. Olfactory and gustatory pre-exposure and subsequent behavioural tests were carried out to reveal possible intra- and cross-modal effects. Attraction to pheromone, monitored with a locomotion compensator, increased after exposure to olfactory and gustatory stimuli. Behavioural responses to sucrose, investigated using the proboscis extension reflex, increased equally after pre-exposure to olfactory and gustatory cues. Pheromone-specific neurons in the brain and antennal gustatory neurons did, however, not change their sensitivity after sucrose exposure. The observed intra- and reciprocal cross-modal effects of pre-exposure may represent a new form of stimulus-nonspecific general sensitization originating from modifications at higher sensory processing levels.

Environment sensitive cracking in pressure boundary materials of light water reactors

International Nuclear Information System (INIS)

Hanninen, H.; Aho-Mantila, I.; Torronen, K.

1987-08-01

A review of the various forms of environment sensitive cracking in pressure boundary materials of light water reactors is presented. The available methods and the most promising future possibilities of preventive maintenance to counteract the environmental degradation are evaluated. Environment sensitive cracking is considered from the metallurgical, mechanical and environmental point of view. The main emphasis is on intergranular stress corrosion cracking of austenitic stainless steels and high strength Ni-base alloys as well as on corrosion fatigue of low alloy and stainless steels. Additionally, some general ideas on how to predict, reduce, monitor or eliminate environment sensitive cracking in service are presented

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation

Energy Technology Data Exchange (ETDEWEB)

Shirai, Hidenori; Fujimori, Hiroaki [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Gunji, Akemi [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Maeda, Daisuke [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Hirai, Takahisa [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Department of Radiation Oncology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Poetsch, Anna R. [ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Harada, Hiromi [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Yoshida, Tomoko [Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Kyoritsu College of Pharmacy, 1-5-30 Shibakoen, Minatoku, Tokyo 105-8512 (Japan); Sasai, Keisuke [Department of Radiation Oncology, Juntendo University Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 (Japan); Okayasu, Ryuichi [International Open Laboratory, National Institute of Radiological Science, 4-9-1 Anagawa, Inage, Chiba 263-8555 (Japan); Masutani, Mitsuko, E-mail: mmasutan@ncc.go.jp [Division of Genome Stability Research, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); Biochemistry Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan); ADP-Ribosylation in Oncology Project, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045 (Japan)

2013-05-24

Highlights: •Parg{sup −/−} ES cells were more sensitive to γ-irradiation than Parp-1{sup −/−} ES cells. •Parg{sup −/−} cells were more sensitive to carbon-ion irradiation than Parp-1{sup −/−} cells. •Parg{sup −/−} cells showed defects in DSB repair after carbon-ion irradiation. •PAR accumulation was enhanced after carbon-ion irradiation compared to γ-irradiation. -- Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg{sup −/−} and poly(ADP-ribose) polymerase-1 deficient (Parp-1{sup −/−}) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg{sup −/−} cells were more sensitive to γ-irradiation than Parp-1{sup −/−} cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg{sup −/−} cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg{sup −/−} ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1{sup −/−} cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg{sup −/−} ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg{sup −/−} cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1{sup −/−} cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was

Parg deficiency confers radio-sensitization through enhanced cell death in mouse ES cells exposed to various forms of ionizing radiation

International Nuclear Information System (INIS)

Shirai, Hidenori; Fujimori, Hiroaki; Gunji, Akemi; Maeda, Daisuke; Hirai, Takahisa; Poetsch, Anna R.; Harada, Hiromi; Yoshida, Tomoko; Sasai, Keisuke; Okayasu, Ryuichi; Masutani, Mitsuko

2013-01-01

Highlights: •Parg −/− ES cells were more sensitive to γ-irradiation than Parp-1 −/− ES cells. •Parg −/− cells were more sensitive to carbon-ion irradiation than Parp-1 −/− cells. •Parg −/− cells showed defects in DSB repair after carbon-ion irradiation. •PAR accumulation was enhanced after carbon-ion irradiation compared to γ-irradiation. -- Abstract: Poly(ADP-ribose) glycohydrolase (Parg) is the main enzyme involved in poly(ADP-ribose) degradation. Here, the effects of Parg deficiency on sensitivity to low and high linear-energy-transfer (LET) radiation were investigated in mouse embryonic stem (ES) cells. Mouse Parg −/− and poly(ADP-ribose) polymerase-1 deficient (Parp-1 −/− ) ES cells were used and responses to low and high LET radiation were assessed by clonogenic survival and biochemical and biological analysis methods. Parg −/− cells were more sensitive to γ-irradiation than Parp-1 −/− cells. Transient accumulation of poly(ADP-ribose) was enhanced in Parg −/− cells. Augmented levels of phosphorylated H2AX (γ-H2AX) from early phase were observed in Parg −/− ES cells. The induction level of p53 phophorylation at ser18 was similar in wild-type and Parp-1 −/− cells and apoptotic cell death process was mainly observed in the both genotypes. These results suggested that the enhanced sensitivity of Parg −/− ES cells to γ-irradiation involved defective repair of DNA double strand breaks. The effects of Parg and Parp-1 deficiency on the ES cell response to carbon-ion irradiation (LET13 and 70 keV/μm) and Fe-ion irradiation (200 keV/μm) were also examined. Parg −/− cells were more sensitive to LET 70 keV/μm carbon-ion irradiation than Parp-1 −/− cells. Enhanced apoptotic cell death also accompanied augmented levels of γ-H2AX in a biphasic manner peaked at 1 and 24 h. The induction level of p53 phophorylation at ser18 was not different between wild-type and Parg −/− cells. The augmented

Teaching Form as Form

DEFF Research Database (Denmark)

Keiding, Tina Bering

2012-01-01

understanding of form per se, or, to use an expression from this text, of form as form. This challenge can be reduced to one question: how can design teaching support students in achieving not only the ability to recognize and describe different form-related concepts in existing design (i.e. analytical...

Piezo proteins are pore-forming subunits of mechanically activated channels.

Science.gov (United States)

Coste, Bertrand; Xiao, Bailong; Santos, Jose S; Syeda, Ruhma; Grandl, Jörg; Spencer, Kathryn S; Kim, Sung Eun; Schmidt, Manuela; Mathur, Jayanti; Dubin, Adrienne E; Montal, Mauricio; Patapoutian, Ardem

2012-02-19

Mechanotransduction has an important role in physiology. Biological processes including sensing touch and sound waves require as-yet-unidentified cation channels that detect pressure. Mouse Piezo1 (MmPiezo1) and MmPiezo2 (also called Fam38a and Fam38b, respectively) induce mechanically activated cationic currents in cells; however, it is unknown whether Piezo proteins are pore-forming ion channels or modulate ion channels. Here we show that Drosophila melanogaster Piezo (DmPiezo, also called CG8486) also induces mechanically activated currents in cells, but through channels with remarkably distinct pore properties including sensitivity to the pore blocker ruthenium red and single channel conductances. MmPiezo1 assembles as a ∼1.2-million-dalton homo-oligomer, with no evidence of other proteins in this complex. Purified MmPiezo1 reconstituted into asymmetric lipid bilayers and liposomes forms ruthenium-red-sensitive ion channels. These data demonstrate that Piezo proteins are an evolutionarily conserved ion channel family involved in mechanotransduction.

TEMAC, Top Event Sensitivity Analysis

International Nuclear Information System (INIS)

Iman, R.L.; Shortencarier, M.J.

1988-01-01

1 - Description of program or function: TEMAC is designed to permit the user to easily estimate risk and to perform sensitivity and uncertainty analyses with a Boolean expression such as produced by the SETS computer program. SETS produces a mathematical representation of a fault tree used to model system unavailability. In the terminology of the TEMAC program, such a mathematical representation is referred to as a top event. The analysis of risk involves the estimation of the magnitude of risk, the sensitivity of risk estimates to base event probabilities and initiating event frequencies, and the quantification of the uncertainty in the risk estimates. 2 - Method of solution: Sensitivity and uncertainty analyses associated with top events involve mathematical operations on the corresponding Boolean expression for the top event, as well as repeated evaluations of the top event in a Monte Carlo fashion. TEMAC employs a general matrix approach which provides a convenient general form for Boolean expressions, is computationally efficient, and allows large problems to be analyzed. 3 - Restrictions on the complexity of the problem - Maxima of: 4000 cut sets, 500 events, 500 values in a Monte Carlo sample, 16 characters in an event name. These restrictions are implemented through the FORTRAN 77 PARAMATER statement

The step-wise pathway of septin hetero-octamer assembly in budding yeast.

Science.gov (United States)

Weems, Andrew; McMurray, Michael

2017-05-25

Septin proteins bind guanine nucleotides and form rod-shaped hetero-oligomers. Cells choose from a variety of available septins to assemble distinct hetero-oligomers, but the underlying mechanism was unknown. Using a new in vivo assay, we find that a stepwise assembly pathway produces the two species of budding yeast septin hetero-octamers: Cdc11/Shs1-Cdc12-Cdc3-Cdc10-Cdc10-Cdc3-Cdc12-Cdc11/Shs1. Rapid GTP hydrolysis by monomeric Cdc10 drives assembly of the core Cdc10 homodimer. The extended Cdc3 N terminus autoinhibits Cdc3 association with Cdc10 homodimers until prior Cdc3-Cdc12 interaction. Slow hydrolysis by monomeric Cdc12 and specific affinity of Cdc11 for transient Cdc12•GTP drive assembly of distinct trimers, Cdc11-Cdc12-Cdc3 or Shs1-Cdc12-Cdc3. Decreasing the cytosolic GTP:GDP ratio increases the incorporation of Shs1 vs Cdc11, which alters the curvature of filamentous septin rings. Our findings explain how GTP hydrolysis controls septin assembly, and uncover mechanisms by which cells construct defined septin complexes.

Crystal structures of Hsp104 N-terminal domains from Saccharomyces cerevisiae and Candida albicans suggest the mechanism for the function of Hsp104 in dissolving prions

Energy Technology Data Exchange (ETDEWEB)

Wang, Peng; Li, Jingzhi; Weaver, Clarissa; Lucius, Aaron; Sha, Bingdong

2017-03-31

Hsp104 is a yeast member of the Hsp100 family which functions as a molecular chaperone to disaggregate misfolded polypeptides. To understand the mechanism by which the Hsp104 N-terminal domain (NTD) interacts with its peptide substrates, crystal structures of the Hsp104 NTDs fromSaccharomyces cerevisiae(ScHsp104NTD) andCandida albicans(CaHsp104NTD) have been determined at high resolution. The structures of ScHsp104NTD and CaHsp104NTD reveal that the yeast Hsp104 NTD may utilize a conserved putative peptide-binding groove to interact with misfolded polypeptides. In the crystal structures ScHsp104NTD forms a homodimer, while CaHsp104NTD exists as a monomer. The consecutive residues Gln105, Gln106 and Lys107, and Lys141 around the putative peptide-binding groove mediate the monomer–monomer interactions within the ScHsp104NTD homodimer. Dimer formation by ScHsp104NTD suggests that the Hsp104 NTD may specifically interact with polyQ regions of prion-prone proteins. The data may reveal the mechanism by which Hsp104 NTD functions to suppress and/or dissolve prions.

Molecular Buffers Permit Sensitivity Tuning and Inversion of Riboswitch Signals

DEFF Research Database (Denmark)

Rugbjerg, Peter; Genee, Hans Jasper; Jensen, Kristian

2016-01-01

transcription factor, while interacting DNA-binding domains mediate the transduction of signal and form an interacting molecular buffer. The molecular buffer system enables modular signal inversion through integration with repressor modules. Further, tuning of input sensitivity was achieved through perturbation...

Substitutions in conserved regions preceding and within the linker affect activity and flexibility of tRNase ZL, the long form of tRNase Z.

Directory of Open Access Journals (Sweden)

Makenzie Saoura

Full Text Available The enzyme tRNase Z, a member of the metallo-β-lactamase family, endonucleolytically removes 3' trailers from precursor tRNAs, preparing them for CCA addition and aminoacylation. The short form of tRNase Z, tRNase ZS, functions as a homodimer and is found in all prokaryotes and some eukaryotes. The long form, tRNase ZL, related to tRNase ZS through tandem duplication and found only in eukaryotes, possesses ~2,000-fold greater catalytic efficiency than tRNase ZS. tRNase ZL consists of related but diverged amino and carboxy domains connected by a flexible linker (also referred to as a flexible tether and functions as a monomer. The amino domain retains the flexible arm responsible for substrate recognition and binding while the carboxy domain retains the active site. The linker region was explored by Ala-scanning through two conserved regions of D. melanogaster tRNase Z: NdomTprox, located at the carboxy end of the amino domain proximal to the linker, and Tflex, a flexible site in the linker. Periodic substitutions in a hydrophobic patch (F329 and L332 at the carboxy end of NdomTprox show 2,700 and 670-fold impairment relative to wild type, respectively, accompanied by reduced linker flexibility at N-T inside the Ndom- linker boundary. The Ala substitution for N378 in the Tflex region has 10-fold higher catalytic efficiency than wild type and locally decreased flexibility, while the Ala substitution at R382 reduces catalytic efficiency ~50-fold. These changes in pre-tRNA processing kinetics and protein flexibility are interpreted in light of a recent crystal structure for S. cerevisiae tRNase Z, suggesting transmission of local changes in hydrophobicity into the skeleton of the amino domain.

Stress analysis of biomass fuel molding machine piston type stamping forming cone

Directory of Open Access Journals (Sweden)

Wu Gaofeng

2015-01-01

Full Text Available It is established the ram biomass straw machine as the analysis object in this paper,the molding machine cones of stress in the forming process of the analysis of the system. We used pottery instead of Wear-resistant cast iron for improving the performance of forming sleeve. The structure of the forming sleeve was analyzed with the mechanical module of a soft named Pro/engineer in this paper. The result indicated that the program was feasible. With the sensitivity analysis we identified the suitable angle for the sleeve.

Biofilm formation and antimicrobial sensitivity of lactobacilli contaminants from sugarcane-based fuel ethanol fermentation.

Science.gov (United States)

Dellias, Marina de Toledo Ferraz; Borges, Clóvis Daniel; Lopes, Mário Lúcio; da Cruz, Sandra Helena; de Amorim, Henrique Vianna; Tsai, Siu Mui

2018-02-24

Industrial ethanol fermentation is subject to bacterial contamination that causes significant economic losses in ethanol fuel plants. Chronic contamination has been associated with biofilms that are normally more resistant to antimicrobials and cleaning efforts than planktonic cells. In this study, contaminant species of Lactobacillus isolated from biofilms (source of sessile cells) and wine (source of planktonic cells) from industrial and pilot-scale fermentations were compared regarding their ability to form biofilms and their sensitivity to different antimicrobials. Fifty lactobacilli were isolated and the most abundant species were Lactobacillus casei, Lactobacillus fermentum and Lactobacillus plantarum. The majority of the isolates (87.8%) were able to produce biofilms in pure culture. The capability to form biofilms and sensitivity to virginiamycin, monensin and beta-acids from hops, showed inter- and intra-specific variability. In the pilot-scale fermentation, Lactobacillus brevis, L. casei and the majority of L. plantarum isolates were less sensitive to beta-acids than their counterparts from wine; L. brevis isolates from biofilms were also less sensitive to monensin when compared to the wine isolates. Biofilm formation and sensitivity to beta-acids showed a positive and negative correlation for L. casei and L. plantarum, respectively.

Nickel acts as an adjuvant during cobalt sensitization

DEFF Research Database (Denmark)

Bonefeld, Charlotte Menne; Nielsen, Morten Milek; Vennegaard, Marie T.

2015-01-01

Metal allergy is the most frequent form of contact allergy with nickel and cobalt being the main culprits. Typically, exposure comes from metal-alloys where nickel and cobalt co-exist. Importantly, very little is known about how co-exposure to nickel and cobalt affects the immune system. We...... investigated these effects by using a recently developed mouse model. Mice were epicutaneously sensitized with i) nickel alone, ii) nickel in the presence of cobalt, iii) cobalt alone, or iv) cobalt in the presence of nickel, and then followed by challenge with either nickel or cobalt alone. We found...... that sensitization with nickel alone induced more local inflammation than cobalt alone as measured by increased ear-swelling. Furthermore, the presence of nickel during sensitization to cobalt led to a stronger challenge response to cobalt as seen by increased ear-swelling and increased B and T cell responses...

The E. coli monothiol glutaredoxin GrxD forms homodimeric and heterodimeric FeS cluster containing complexes.

Science.gov (United States)

Yeung, N; Gold, B; Liu, N L; Prathapam, R; Sterling, H J; Willams, E R; Butland, G

2011-10-18

Monothiol glutaredoxins (mono-Grx) represent a highly evolutionarily conserved class of proteins present in organisms ranging from prokaryotes to humans. Mono-Grxs have been implicated in iron sulfur (FeS) cluster biosynthesis as potential scaffold proteins and in iron homeostasis via an FeS-containing complex with Fra2p (homologue of E. coli BolA) in yeast and are linked to signal transduction in mammalian systems. However, the function of the mono-Grx in prokaryotes and the nature of an interaction with BolA-like proteins have not been established. Recent genome-wide screens for E. coli genetic interactions reported the synthetic lethality (combination of mutations leading to cell death; mutation of only one of these genes does not) of a grxD mutation when combined with strains defective in FeS cluster biosynthesis (isc operon) functions [Butland, G., et al. (2008) Nature Methods 5, 789-795]. These data connected the only E. coli mono-Grx, GrxD to a potential role in FeS cluster biosynthesis. We investigated GrxD to uncover the molecular basis of this synthetic lethality and observed that GrxD can form FeS-bound homodimeric and BolA containing heterodimeric complexes. These complexes display substantially different spectroscopic and functional properties, including the ability to act as scaffold proteins for intact FeS cluster transfer to the model [2Fe-2S] acceptor protein E. coli apo-ferredoxin (Fdx), with the homodimer being significantly more efficient. In this work, we functionally dissect the potential cellular roles of GrxD as a component of both homodimeric and heterodimeric complexes to ultimately uncover if either of these complexes performs functions linked to FeS cluster biosynthesis. © 2011 American Chemical Society

Monte Carlo Calculation of Sensitivities to Secondaries' Angular Distributions

International Nuclear Information System (INIS)

Perel, R.L.

2003-01-01

An algorithm for Monte Carlo calculation of sensitivities of responses to secondaries' angular distributions (SAD) is developed, based on the differential operator approach. The algorithm was formulated for the sensitivity to Legendre coefficients of the SAD and is valid even in cases where the actual representation of SAD is not in the form of a Legendre series. The algorithm was implemented, for point- or ring-detectors, in a local version of the code MCNP. Numerical tests were performed to validate the algorithm and its implementation. In addition, an algorithm specific for the Kalbach-Mann representation of SAD is presented

Working with simulated forms of interaction in health care education

DEFF Research Database (Denmark)

Nordentoft, Helle Merete; Olesen, Lektor Birgitte Ravn

This paper argues that role-play as a simulated form of interaction - live and performed on video - is a creative method which has the potential to generate and support authentic dialogues in practice. In the paper we draw on experiences from 6 interdisciplinary workshops at a Danish hospital...... in which role-play of practice situations - both live and performed on video - formed the launching-pad for participants’ oral and written reflections. Our findings show that role-play has the potential to 1) develop professionals’ sensitivity to the significance of unexpected, embodied and emotional...

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs

OpenAIRE

Puvanenthiran, Soozana; Essapen, Sharadah; Seddon, Alan M.; Modjtahedi, Helmout

2016-01-01

Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer s...

Literatura chicana: Vida en busca de forma (Chicano Literature: Life in Search of Form).

Science.gov (United States)

Rivera, Tomas

The Chicano culture is searching for appropriate expression in art forms and literature. The Chicano novel and essay, often written in English, seem directed toward the North American public. The short story is the most varied in viewpoint and most versatile in form. Poetry captures the Chicano sensitivity. It is almost impossible to note the…

How to Determine the Increasing Returns Sensitivity of Your Industry?

NARCIS (Netherlands)

M.H. Klein (Martin); E. den Hartigh; H.R. Commandeur (Harry); F. Langerak (Fred)

2004-01-01

textabstractIncreasing returns means that self-reinforcing mechanisms are at work within firms and markets. These mechanisms come in four forms: scale effects, learning effects, network effects and social interaction effects. Some industries are more sensitive to increasing returns than others. It

A conceptualisation framework for building consensus on environmental sensitivity.

Science.gov (United States)

González Del Campo, Ainhoa

2017-09-15

Examination of the intrinsic attributes of a system that render it more or less sensitive to potential stressors provides further insight into the baseline environment. In impact assessment, sensitivity of environmental receptors can be conceptualised on the basis of their: a) quality status according to statutory indicators and associated thresholds or targets; b) statutory protection; or c) inherent risk. Where none of these considerations are pertinent, subjective value judgments can be applied to determine sensitivity. This pragmatic conceptual framework formed the basis of a stakeholder consultation process for harmonising degrees of sensitivity of a number of environmental criteria. Harmonisation was sought to facilitate their comparative and combined analysis. Overall, full or wide agreement was reached on relative sensitivity values for the large majority of the reviewed criteria. Consensus was easier to reach on some themes (e.g. biodiversity, water and cultural heritage) than others (e.g. population and soils). As anticipated, existing statutory measures shaped the outcomes but, ultimately, knowledge-based values prevailed. The agreed relative sensitivities warrant extensive consultation but the conceptual framework provides a basis for increasing stakeholder consensus and objectivity of baseline assessments. This, in turn, can contribute to improving the evidence-base for characterising the significance of potential impacts. Copyright © 2017 Elsevier Ltd. All rights reserved.

Sensitivity of aerosol loading and properties to cloudiness

Science.gov (United States)

Iversen, T.; Seland, O.; Kirkevag, A.; Kristjansson, J. E.

2005-12-01

Clouds influence aerosols in various ways. Sulfate is swiftly produced in liquid phase provided there is both sulfur dioxide and oxidants available. Nucleation and Aitken mode aerosol particles efficiently grow in size by collision and coagulation with cloud droplets. When precipitation is formed, aerosol and precursor gases may be quickly removed bay rainout. The dynamics associated with clouds in some cases may swiftly mix aerosols deeply into the troposphere. In some cases Aitken-mode particles may be formed in cloud droplets by splitting agglomerates of particulate matter such as black carbon In this presentation we will discuss how global cloudiness may influence the burden, residence time, and spatial distribution of sulfate, black carbon and particulate organic matter. A similar physico-chemical scheme for there compounds has been implemented in three generations of the NCAR community climate model (CCM3, CAM2 and CAM3). The scheme is documented in the literature and is a part of the Aerocom-intercomparison. There are many differences between these models. With respect to aerosols, a major difference is that CAM3 has a considerably higher global cloud volume and more then twice the amount of cloud water than CAM2 and CCM3. Atmospheric simulations have been made with prescribed ocean temperatures. It is slightly surprising to discover that certain aspects of the aerosols are not particularly sensitive to these differences in cloud availability. This sensitivity will be compared to sensitivities with respect to processing in deep convective clouds.

L-form transformation phenomenon in Mycobacterium tuberculosis associated with drug tolerance to ethambutol

Directory of Open Access Journals (Sweden)

Georgi Slavchev

2016-01-01

Full Text Available Objective/background: Cell wall-deficient bacterial forms (L-forms may occur along with resistance to factors that trigger their appearance. It is of interest to study the relationship between the L-form transformation of Mycobacterium tuberculosis and the exhibition of drug tolerance to ethambutol (EMB, an inhibitor of cell wall synthesis. Methods: L-form variant was produced from a sensitive EMB strain of M. Tuberculosis through a cryogenic stress treatment protocol and was subsequently cultivated in Middlebrook 7H9 semisolid medium, containing EMB in a minimal inhibitory concentration of 2 mg/L. Susceptibility to EMB of the parental strain and its L-form variant was evaluated phenotypically and using polymerase chain reaction-restriction fragment length polymorphism assay targeting a mutation in the embB306 gene fragment. Results: In contrast to the sensitivity to EMB of the parental strain, its L-form variant showed phenotypic resistance to high concentrations of EMB (16 mg/L, but the mutation in embB306 was not found. Electron microscopy observation of the L-form variant showed a heterogenic population of bacteria, with different degrees of cell wall deficiency, as well as cells of protoplastic type without cell walls. Of special interest were the observed capsule-like structures around the L-form cells and the biofilm-like matrix produced by the L-form population. Conclusion: We suggest that the expression of phenotypic resistance to EMB in M. Tuberculosis can be associated with alterations or loss of cell walls in L-form bacteria, respectively, which results in a lack of a specific target for EMB action. In addition, production of capsule-like structures and biofilm matrix by L-forms could contribute to their resistance and survival in the presence of antibacterial agents.

Effects of the d-state quarks on the nucleon electric form factors

International Nuclear Information System (INIS)

Oh, Y.J.; Kong, K.J.; Cheon, I.T.

1987-11-01

Considering the d-orbital excitation of a quark in the bag, we calculate the nucleon electric form factors in the cloudy bag model. In these calculations, we have taken into account the πNN, πΔN and πγ form factors though neglecting the c.m. correction. It turns out that the neutron charge form factor is very sensitive to the d-state quark admixture in the overall region of the momentum transfer but the proton charge form factor remains unchanged. Taking the d-state quark admixture in the intermediate state baryons, we can obtain the nucleon rms radii in remarkable agreement with the experimental values. We also investigate the roles of Δ particles in the nucleon charge form factors. (author). 20 refs, 10 figs

Computational Methods for Sensitivity and Uncertainty Analysis in Criticality Safety

International Nuclear Information System (INIS)

Broadhead, B.L.; Childs, R.L.; Rearden, B.T.

1999-01-01

Interest in the sensitivity methods that were developed and widely used in the 1970s (the FORSS methodology at ORNL among others) has increased recently as a result of potential use in the area of criticality safety data validation procedures to define computational bias, uncertainties and area(s) of applicability. Functional forms of the resulting sensitivity coefficients can be used as formal parameters in the determination of applicability of benchmark experiments to their corresponding industrial application areas. In order for these techniques to be generally useful to the criticality safety practitioner, the procedures governing their use had to be updated and simplified. This paper will describe the resulting sensitivity analysis tools that have been generated for potential use by the criticality safety community

Cytochrome P450-mediated activation of the fragrance compound geraniol forms potent contact allergens

International Nuclear Information System (INIS)

Hagvall, Lina; Baron, Jens Malte; Boerje, Anna; Weidolf, Lars; Merk, Hans; Karlberg, Ann-Therese

2008-01-01

Contact sensitization is caused by low molecular weight compounds which penetrate the skin and bind to protein. In many cases, these compounds are activated to reactive species, either by autoxidation on exposure to air or by metabolic activation in the skin. Geraniol, a widely used fragrance chemical, is considered to be a weak allergen, although its chemical structure does not indicate it to be a contact sensitizer. We have shown that geraniol autoxidizes and forms allergenic oxidation products. In the literature, it is suggested but not shown that geraniol could be metabolically activated to geranial. Previously, a skin-like CYP cocktail consisting of cutaneous CYP isoenzymes, was developed as a model system to study cutaneous metabolism. In the present study, we used this system to investigate CYP-mediated activation of geraniol. In incubations with the skin-like CYP cocktail, geranial, neral, 2,3-epoxygeraniol, 6,7-epoxygeraniol and 6,7-epoxygeranial were identified. Geranial was the main metabolite formed followed by 6,7-epoxygeraniol. The allergenic activities of the identified metabolites were determined in the murine local lymph node assay (LLNA). Geranial, neral and 6,7-epoxygeraniol were shown to be moderate sensitizers, and 6,7-epoxygeranial a strong sensitizer. Of the isoenzymes studied, CYP2B6, CYP1A1 and CYP3A5 showed high activities. It is likely that CYP1A1 and CYP3A5 are mainly responsible for the metabolic activation of geraniol in the skin, as they are expressed constitutively at significantly higher levels than CYP2B6. Thus, geraniol is activated through both autoxidation and metabolism. The allergens geranial and neral are formed via both oxidation mechanisms, thereby playing a large role in the sensitization to geraniol

Plane-stress fields for sharp notches in pressure-sensitive materials

International Nuclear Information System (INIS)

Al-Abduljabbar, Abdulhamid

2003-01-01

The effect of pressure sensitive yield on materials toughness can be determined by investigating stress fields around cracks and notches. In this work, fully-developed plastic stress fields around sharp wedge-shaped notches of perfectly-plastic pressure-sensitive materials are investigated for plane-stress case and Mode 1 loading condition. The pressure-sensitive yielding behavior is represented using the Drucker-Prager criterion. Using equilibrium equations, boundary conditions, and the yield criterion, closed-form expressions for stress fields are derived. The analysis covers the gradual change in the notch angle and compares it with the limiting case of a pure horizontal crack. Effects of notch geometry and pressure sensitivity on stress fields are examined by considering different specimen geometries, as well as different levels of pressure sensitivity. Results indicate that while the stress values directly ahead of the notch-tip are not affected, the extent of stress sector at notch front is reduced, thereby causing increase in the radial stress value around the notch. As the pressure sensitivity increases the reduction of the stress sector directly ahead of the notch tip is more evident. Also, for high pressure sensitivity values, introduction of the notch angle reduces the variation of the stress levels. Results are useful for design of structural components. (author)

Central Sensitization-Based Classification for Temporomandibular Disorders: A Pathogenetic Hypothesis

Directory of Open Access Journals (Sweden)

Annalisa Monaco

2017-01-01

Full Text Available Dysregulation of Autonomic Nervous System (ANS and central pain pathways in temporomandibular disorders (TMD is a growing evidence. Authors include some forms of TMD among central sensitization syndromes (CSS, a group of pathologies characterized by central morphofunctional alterations. Central Sensitization Inventory (CSI is useful for clinical diagnosis. Clinical examination and CSI cannot identify the central site(s affected in these diseases. Ultralow frequency transcutaneous electrical nerve stimulation (ULFTENS is extensively used in TMD and in dental clinical practice, because of its effects on descending pain modulation pathways. The Diagnostic Criteria for TMD (DC/TMD are the most accurate tool for diagnosis and classification of TMD. However, it includes CSI to investigate central aspects of TMD. Preliminary data on sensory ULFTENS show it is a reliable tool for the study of central and autonomic pathways in TMD. An alternative classification based on the presence of Central Sensitization and on individual response to sensory ULFTENS is proposed. TMD may be classified into 4 groups: (a TMD with Central Sensitization ULFTENS Responders; (b TMD with Central Sensitization ULFTENS Nonresponders; (c TMD without Central Sensitization ULFTENS Responders; (d TMD without Central Sensitization ULFTENS Nonresponders. This pathogenic classification of TMD may help to differentiate therapy and aetiology.

Paratingent Derivative Applied to the Measure of the Sensitivity in Multiobjective Differential Programming

Directory of Open Access Journals (Sweden)

F. García

2013-01-01

Full Text Available We analyse the sensitivity of differential programs of the form subject to where and are maps whose respective images lie in ordered Banach spaces. Following previous works on multiobjective programming, the notion of -optimal solution is used. The behaviour of some nonsingleton sets of -optimal solutions according to changes of the parameter in the problem is analysed. The main result of the work states that the sensitivity of the program is measured by a Lagrange multiplier plus a projection of its derivative. This sensitivity is measured by means of the paratingent derivative.

Photoperiodism and Crassulacean acid metabolism : III. Different characteristics of the photoperiod-sensitive and non-sensitive isoforms of phosphoenolpyruvate carboxylase and Crassulacean acid metabolism operation.

Science.gov (United States)

Brulfert, J; Queiroz, O

1982-05-01

Sensitivity to glucose-6-P, inorganic phosphate and malate, Km phosphoenolpyruvate (PEP), and the effect of pH were comparatively investigated for phosphoenolpyruvate carboxylase (PEPC, EC 4.1.1.31) extracted along the day-night cycle from leaves of Kalanchoe blossfeldiana v. Poelln. Tom Thumb, grown under different photoperiodic conditions. Under long days, sensitivity to effectors is weak and varies only slightly during the 24h cycle, together with small variations of Km (PEP), ranging from 1.2 to 1.8 mM. The response-curve to pH shows two peaks for pH 7.4 and 8.4. Transfer of the plants to short days established an increase in the sensitivity of the enzyme to the effectors together with the appearance of a day-night variation of this effect, maximum during the day. A clear diurnal oscillation of Km (PEP) is observed from 3.1 mM at the beginning of day (09.00 h) to 0.9 mM at midnight (00.00 h), at pH 7.4. These results complement previous electrophoretic and immunological data by affording enzyme kinetic evidence that short days induce a PEP carboxylase form responsible for full-Crassulacean acid metabolism (CAM) operation which is kinetically different from the photoperiod-sensitive, C3-like form prevailing in young leaves under long days. The results indicate that diurnal enzymic rhythms would improve the efficiency of the metabolic regulatory mechanisms and act as a coordinating factor for the daily and seasonal adaptive operation of CAM.

Nano-CL-20/HMX Cocrystal Explosive for Significantly Reduced Mechanical Sensitivity

Directory of Open Access Journals (Sweden)

Chongwei An

2017-01-01

Full Text Available Spray drying method was used to prepare cocrystals of hexanitrohexaazaisowurtzitane (CL-20 and cyclotetramethylene tetranitramine (HMX. Raw materials and cocrystals were characterized using scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, Raman spectroscopy, and Fourier transform infrared spectroscopy. Impact and friction sensitivity of cocrystals were tested and analyzed. Results show that, after preparation by spray drying method, microparticles were spherical in shape and 0.5–5 µm in size. Particles formed aggregates of numerous tiny plate-like cocrystals, whereas CL-20/HMX cocrystals had thicknesses of below 100 nm. Cocrystals were formed by C–H⋯O bonding between –NO2 (CL-20 and –CH2– (HMX. Nanococrystal explosives exhibited drop height of 47.3 cm, and friction demonstrated explosion probability of 64%. Compared with raw HMX, cocrystals displayed significantly reduced mechanical sensitivity.

[A new class of exciplex-formed probe detect of specific sequence DNA].

Science.gov (United States)

Li, Qing-Yong; Zu, Yuan-Gang; Lü, Hong-Yan; Wang, Li-Min

2009-07-01

The present research was to develop the exciplex-based fluorescence detection of DNA. A SNP-containing region of cytochrome P450 2C9 DNA systems was evaluated to define some of the structural and associated requirement of this new class of exciplex-formed probe, and a 24-base target was selected which contains single-nucleotide polymorphisms (SNP) in genes coding for cytochrome P450. The two probes were all 12-base to give coverage of a 24-base target region to ensure specificity within the human genome. Exciplex partners used in this study were prepared using analogous phosphoramide attachment to the 3'- or 5'-phosphate group of the appropriate oligonucleotide probes. The target effectively assembled its own detector by hybridization from components which were non-fluorescent at the detection wavelength, leading to the huge improvement in terms of decreased background. This research provides details of the effects of different partner, position of partners and different excitation wavelengths for the split-oligonucleotide probe system for exciplex-based fluorescence detection of DNA. This study demonstrates that the emission intensity of the excimer formed by new pyrene derivative is the highest in these excimer and exciplex, and the excimer is easy to be formed and not sensitive to the position of partners. However the exciplex formed by the new pyrene derivative and naphthalene emitted strongly at -505 nm with large Stokes shifts (120-130 nm), and the monomer emission at 390 and 410 nm is nearly zero. Excitation wavelength of 400 nm is the best for I(e505)/I(m410) (exciplex emission at 505 nm/monomer emission at 410 nm) of the exciplex. This method features lower background and high sensitivity. Moreover the exciplex is sensitive to the steric factor, different position of partners and microenvironment, so this exciplex system is promising and could be tried to identify the SNP genes.

Helicity non-conserving form factor of the proton

Energy Technology Data Exchange (ETDEWEB)

Voutier, E.; Furget, C.; Knox, S. [Universite Joseph Fourier, Grenoble (France)] [and others

1994-04-01

The study of the hadron structure in the high Q{sup 2} range contributes to the understanding of the mechanisms responsible for the confinement of quarks and gluons. Among the numerous experimental candidates sensitive to these mechanisms, the helicity non-conserving form factor of the proton is a privileged observable since it is controlled by non-perturbative effects. The authors investigate here the feasibility of high Q{sup 2} measurements of this form factor by means of the recoil polarization method in the context of the CEBAF 8 GeV facility. For that purpose, they discuss the development of a high energy proton polarimeter, based on the H({rvec p},pp) elastic scattering, to be placed at the focal plane of a new hadron spectrometer. It is shown that this experimental method significantly improves the knowledge of the helicity non-conserving form factor of the proton up to 10 GeV{sup 2}/c{sup 2}.

Beyond the GUM: variance-based sensitivity analysis in metrology

International Nuclear Information System (INIS)

Lira, I

2016-01-01

Variance-based sensitivity analysis is a well established tool for evaluating the contribution of the uncertainties in the inputs to the uncertainty in the output of a general mathematical model. While the literature on this subject is quite extensive, it has not found widespread use in metrological applications. In this article we present a succinct review of the fundamentals of sensitivity analysis, in a form that should be useful to most people familiarized with the Guide to the Expression of Uncertainty in Measurement (GUM). Through two examples, it is shown that in linear measurement models, no new knowledge is gained by using sensitivity analysis that is not already available after the terms in the so-called ‘law of propagation of uncertainties’ have been computed. However, if the model behaves non-linearly in the neighbourhood of the best estimates of the input quantities—and if these quantities are assumed to be statistically independent—sensitivity analysis is definitely advantageous for gaining insight into how they can be ranked according to their importance in establishing the uncertainty of the measurand. (paper)

Structural and dynamic studies of the dimerization and DNA-binding domains of the transcription factors v-Myc and Max

International Nuclear Information System (INIS)

Fieber, W.

2001-05-01

In the present work, solution structural and dynamic properties of the dimerization and DNA binding domains of the transcription factors v-Myc and Max were characterized by NMR and CD spectroscopy. It could be demonstrated that v-Myc in the absence of its authentic binding partner Max does not homodimerize, but exists in a monomeric and prestructured form. Two separated α-helical regions in the leucine zipper region and in the basic-H1 region, respectively, could be identified, while the latter appeared to be less stable. Both helices lack stabilizing tertiary side chain interactions and represent exceptional examples for loosely coupled, structured segments in a native protein. The structure of v-Myc is dynamic and can be described as a distribution of conformational substates. Motion within the substates comprise fast (picosecond to nanosecond) local backbone fluctuations like helical fraying, whereas motion between the substates comprise the relative orientation of the two helices and occur at larger time scales (microsecond to millisecond). The preformation of the specific protein and DNA binding sites, leucine zipper and the basic region, presumably allows rapid and accurate recognition of the respective binding partners. v-Myc-Max and Max-Max protein preparations were shown to form stable dimers. Thermodynamic analysis of the dissociation reactions of v-Myc-Max revealed a significant higher stability of the heterodimer than of the Max-Max homodimer over the whole temperature range. It could be demonstrated that the restricted conformational space of the v-Myc bHLHZip domain reduces the entropy penalty associated with dimerization and contributes to the preference of Max to form heterodimers with v-Myc rather than homodimers. (author)

POSSuMUS: a position sensitive scintillating muon SiPM detector

CERN Document Server

Ruschke, Alexander

The development of a modular designed large scale scintillation detector with a two-dimensional position sensitivity is presented in this thesis. This novel POsition Sensitive Scintillating MUon SiPM Detector is named POSSuMUS. The POSSuMUS detector is capable to determine the particle’s position in two space dimensions with a fast trigger capability. Each module is constructed from two trapezoidal shaped plastic scintillators to form one rectangular shaped detector module. Both trapezoids are optically insulated against each other. In both trapezoids the scintillation light is collected by plastic fibers and guided towards silicon photomultipliers (SiPMs). SiPMs are light sensors which are capable to detect even smallest amounts of light. By combining several detector modules, position sensitive areas from 100 cm2 to few m2 are achievable with few readout channels. Therefore, POSSuMUS provides a cost effective detector concept. The position sensitivity along the trapezoidal geometry of one detector module ...

Improved Sensitivity Relations in State Constrained Optimal Control

International Nuclear Information System (INIS)

Bettiol, Piernicola; Frankowska, Hélène; Vinter, Richard B.

2015-01-01

Sensitivity relations in optimal control provide an interpretation of the costate trajectory and the Hamiltonian, evaluated along an optimal trajectory, in terms of gradients of the value function. While sensitivity relations are a straightforward consequence of standard transversality conditions for state constraint free optimal control problems formulated in terms of control-dependent differential equations with smooth data, their verification for problems with either pathwise state constraints, nonsmooth data, or for problems where the dynamic constraint takes the form of a differential inclusion, requires careful analysis. In this paper we establish validity of both ‘full’ and ‘partial’ sensitivity relations for an adjoint state of the maximum principle, for optimal control problems with pathwise state constraints, where the underlying control system is described by a differential inclusion. The partial sensitivity relation interprets the costate in terms of partial Clarke subgradients of the value function with respect to the state variable, while the full sensitivity relation interprets the couple, comprising the costate and Hamiltonian, as the Clarke subgradient of the value function with respect to both time and state variables. These relations are distinct because, for nonsmooth data, the partial Clarke subdifferential does not coincide with the projection of the (full) Clarke subdifferential on the relevant coordinate space. We show for the first time (even for problems without state constraints) that a costate trajectory can be chosen to satisfy the partial and full sensitivity relations simultaneously. The partial sensitivity relation in this paper is new for state constraint problems, while the full sensitivity relation improves on earlier results in the literature (for optimal control problems formulated in terms of Lipschitz continuous multifunctions), because a less restrictive inward pointing hypothesis is invoked in the proof, and because

Spectrophotometric Determination of Labetalol and Lercanidipine in Pure Form and in Pharmaceutical Preparations Using Ferric-1,10-Phenanthroline

OpenAIRE

Abu El-Enin, M. A.; El-Wasseef, D. R.; El-Sherbiny, D. T.; El-Ashry, S. M.

2009-01-01

A simple and sensitive spectrophotometric method was developed for the determination of labetalol HCl (LBT) and lercanidipine HCl (LER) in pure form and in dosage forms. The method was based upon oxidation of the LBT and LER with Fe+3 and the estimation of the produced Fe+2 with 1,10-phenanthroline. The absorbance of the tris(1,10-phenanthroline) Fe+2 complex was measured at 510 nm. Reaction conditions were optimized to obtain colored complex of higher sensitivity and longer stability. The ab...

Fructose suppresses uric acid excretion to the intestinal lumen as a result of the induction of oxidative stress by NADPH oxidase activation.

Science.gov (United States)

Kaneko, Chihiro; Ogura, Jiro; Sasaki, Shunichi; Okamoto, Keisuke; Kobayashi, Masaki; Kuwayama, Kaori; Narumi, Katsuya; Iseki, Ken

2017-03-01

A high intake of fructose increases the risk for hyperuricemia. It has been reported that long-term fructose consumption suppressed renal uric acid excretion and increased serum uric acid level. However, the effect of single administration of fructose on excretion of uric acid has not been clarified. We used male Wistar rats, which were orally administered fructose (5g/kg). Those rats were used in each experiment at 12h after administration. Single administration of fructose suppressed the function of ileal uric acid excretion and had no effect on the function of renal uric acid excretion. Breast cancer resistance protein (BCRP) predominantly contributes to intestinal excretion of uric acid as an active homodimer. Single administration of fructose decreased BCRP homodimer level in the ileum. Moreover, diphenyleneiodonium (DPI), an inhibitor of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), recovered the suppression of the function of ileal uric acid excretion and the Bcrp homodimer level in the ileum of rats that received single administration of fructose. Single administration of fructose decreases in BCRP homodimer level, resulting in the suppression the function of ileal uric acid excretion. The suppression of the function of ileal uric acid excretion by single administration of fructose is caused by the activation of Nox. The results of our study provide a new insight into the mechanism of fructose-induced hyperuricemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Temperature-sensitive elastin-mimetic dendrimers: Effect of peptide length and dendrimer generation to temperature sensitivity.

Science.gov (United States)

Kojima, Chie; Irie, Kotaro; Tada, Tomoko; Tanaka, Naoki

2014-06-01

Dendrimers are synthetic macromolecules with unique structure, which are a potential scaffold for peptides. Elastin is one of the main components of extracellular matrix and a temperature-sensitive biomacromolecule. Previously, Val-Pro-Gly-Val-Gly peptides have been conjugated to a dendrimer for designing an elastin-mimetic dendrimer. In this study, various elastin-mimetic dendrimers using different length peptides and different dendrimer generations were synthesized to control the temperature dependency. The elastin-mimetic dendrimers formed β-turn structure by heating, which was similar to the elastin-like peptides. The elastin-mimetic dendrimers exhibited an inverse phase transition, largely depending on the peptide length and slightly depending on the dendrimer generation. The elastin-mimetic dendrimers formed aggregates after the phase transition. The endothermal peak was observed in elastin-mimetic dendrimers with long peptides, but not with short ones. The peptide length and the dendrimer generation are important factors to tune the temperature dependency on the elastin-mimetic dendrimer. Copyright © 2013 Wiley Periodicals, Inc.

Validation of the AQT Color-Form Additive Model for Screening and Monitoring Pharmacological Treatment of ADHD

Science.gov (United States)

Nielsen, Niels Peter; Wiig, Elisabeth Hemmersam

2013-01-01

Objective:This retrospective study used A Quick Test of Cognitive Speed (AQT) processing-speed and efficiency measures for evaluating sensitivity and monitoring effects during pharmacological treatment of adults with ADHD. Method: Color (C), form (F), and color-form (CF) combination naming were administered to 69 adults during outpatient…

Technique for sensitivity analysis of space- and energy-dependent burn-up calculations

International Nuclear Information System (INIS)

Williams, M.L.; White, J.R.

1979-01-01

A practical method is presented for sensitivity analysis of the very complex, space-energy dependent burn-up equations, in which the neutron and nuclide fields are coupled nonlinearly. The adjoint burn-up equations that are given are in a form which can be directly implemented into multi-dimensional depletion codes, such as VENTURE/BURNER. The data sensitivity coefficients can be used to determine the effect of data uncertainties on time-dependent depletion responses. Initial condition sensitivity coefficients provide a very effective method for computing the change in end of cycle parameters (such as k/sub eff/, fissile inventory, etc.) due to changes in nuclide concentrations at beginning of cycle

A Sensitivity Analysis On The Springback Behavior Of The Unconstrained Bending Problem

International Nuclear Information System (INIS)

Meinders, T.; Konter, A.W.A.; Meijers, S.E.; Atzema, E.H.; Kappert, H.

2005-01-01

Sheet metal forming software is commonly used in the automotive and sheet metal sectors to support the design stage. However, the ability of the currently available software to accurately predict springback is limited. A sensitivity analysis of the springback behavior of a simple product is performed to gain more knowledge into the various factors contributing to the predictability of springback. The sensitivity analysis comprises both numerical and physical aspects and the most important results are reported in this paper

Influence of pre-deformation, sensitization and oxidation in high temperature water on corrosion resistance of AISI 304 stainless steel

Energy Technology Data Exchange (ETDEWEB)

Lv, Jinlong, E-mail: ljltsinghua@126.com [Beijing Key Laboratory of Fine Ceramics, Institute of Nuclear and New Energy Technology, Tsinghua University, Zhongguancun Street, Haidian District, Beijing 100084 (China); State Key Lab of New Ceramic and Fine Processing, Tsinghua University, Beijing 100084 (China); Liang, Tongxiang [Beijing Key Laboratory of Fine Ceramics, Institute of Nuclear and New Energy Technology, Tsinghua University, Zhongguancun Street, Haidian District, Beijing 100084 (China); State Key Lab of New Ceramic and Fine Processing, Tsinghua University, Beijing 100084 (China); Luo, Hongyun [Key Laboratory of Aerospace Materials and Performance (Ministry of Education), School of Materials Science and Engineering, Beijing University of Aeronautics and Astronautics, Xueyuan Road 37, Beijing 100191 (China)

2016-12-01

Highlights: • The pre-strain accelerated desensitization and sensitization for austenitic stainless steels. • Low temperature sensitization (carbide precipitation) induced α′-martensite. • The sensitization level could affect directly corrosion resistance of the oxide film. - Abstract: The effects of pre-deformation on sensitization of AISI 304 stainless steel were investigated by the double loop electrochemical potentiokinetic reactivation test. The effects of pre-deformation and sensitization on high temperature oxidized film formed in high temperature water were analyzed by a XRD and SEM. The electrochemical impedance spectroscopy at room temperature was used to study corrosion resistance of oxidized film. The point defect density of oxidized film was calculated by Mott–Schottky plots. The results showed that the value of the degree of sensitization first decreased and then slight increased with the increasing of engineering strain. Moreover, low temperature promoted to form sensitization induced “secondary” α′-martensite. The sample with 20% engineering strain had higher impedance value than other samples. The result was supported by further Mott–Schottky experiments. Considering increased α′-martensite with the increasing of strain, the results of the impedance were more consistent with values of the degree of sensitization.

A position sensitive parallel plate avalanche counter

International Nuclear Information System (INIS)

Lombardi, M.; Tan Jilian; Potenza, R.; D'amico, V.

1986-01-01

A position sensitive parallel plate avalanche counter with a distributed constant delay-line-cathode (PSAC) is described. The strips formed on the printed board were served as the cathode and the delay line for readout of signals. The detector (PSAC) was operated in isobutane gas at the pressure range from 10 to 20 torr. The position resolution is better than 1 mm and the time resolution is about 350 ps, for 252 Cf fission-spectrum source

Sensitization to allergens of domestic animals

OpenAIRE

A. N. Pampura; E. E. Varlamov; N. G. Konyukova

2018-01-01

At present, sensitization to airborne allergens in domestic animals is absolutely rightly considered one of the key risk factors for the development of allergic rhinitis and bronchial asthma, as well as largely determines the development of severe forms of atopic dermatitis and respiratory allergosis. Of particularimportance isthe fact that, unlike othertriggers, the elimination of allergensin domestic animals is often associated with internal resistance from patients. The article presents th...

Nuclear waste form risk assessment for US defense waste at Savannah River Plant. Annual report fiscal year 1980

International Nuclear Information System (INIS)

Cheung, H.; Jackson, D.D.; Revelli, M.A.

1981-07-01

Waste form dissolution studies and preliminary performance analyses were carried out to contribute a part of the data needed for the selection of a waste form for the disposal of Savannah River Plant defense waste in a deep geologic repository. The first portion of this work provides descriptions of the chemical interactions between the waste form and the geologic environment. We reviewed critically the dissolution/leaching data for borosilicate glass and SYNROC. Both chemical kinetic and thermodynamic models were developed to describe the dissolution process of these candidate waste forms so as to establish a fundamental basis for interpretation of experimental data and to provide directions for future experiments. The complementary second portion of this work is an assessment of the impacts of alternate waste forms upon the consequences of disposal in various proposed geological media. Employing systems analysis methodology, we began to evaluate the performance of a generic waste form for the case of a high risk scenario for a bedded salt repository. Results of sensitivity analysis, uncertainty analyses, and sensitivity to uncertainty analysis are presented

Increasing incidence of hypothyroidism within one year after radioiodine therapy for toxic diffuse goiter

International Nuclear Information System (INIS)

Von Hofe, S.E.; Dorfman, S.G.; Carrette, R.F.; Young, R.L.

1978-01-01

Patients treated with 10 mCi of I-131 for toxic diffuse goiter in the period January 1974--June 1976 were evaluated for development of hypothyroidism. Fifty percent were hypothyroid within 3 months and 69 percent within 1 year of treatment. Our data suggest that there is a higher incidence of hypothyroidism after standard doses of I-131 in the 1970s as contrasted with treatment groups in the 1950s and 1960s. The pathophysiology of this increased incidence is not known with certainty; however, infrequent use of thionamide medication, together with recent increases in dietary iodine, may render the gland more radiosensitive

Propagation of errors from the sensitivity image in list mode reconstruction

International Nuclear Information System (INIS)

Qi, Jinyi; Huesman, Ronald H.

2003-01-01

List mode image reconstruction is attracting renewed attention. It eliminates the storage of empty sinogram bins. However, a single back projection of all LORs is still necessary for the pre-calculation of a sensitivity image. Since the detection sensitivity is dependent on the object attenuation and detector efficiency, it must be computed for each study. Exact computation of the sensitivity image can be a daunting task for modern scanners with huge numbers of LORs. Thus, some fast approximate calculation may be desirable. In this paper, we theoretically analyze the error propagation from the sensitivity image into the reconstructed image. The theoretical analysis is based on the fixed point condition of the list mode reconstruction. The non-negativity constraint is modeled using the Kuhn-Tucker condition. With certain assumptions and the first order Taylor series approximation, we derive a closed form expression for the error in the reconstructed image as a function of the error in the sensitivity image. The result provides insights on what kind of error might be allowable in the sensitivity image. Computer simulations show that the theoretical results are in good agreement with the measured results

Sensitization of Naturally Aged Aluminum 5083 Armor Plate

Science.gov (United States)

2015-07-29

5 - 1 - SENSITIZATION OF NATURALLY AGED ALUMINUM 5083 ARMOR PLATE INTRODUCTION Aluminum -magnesium alloys are important for both ship...boundaries [3,4]. The magnesium-rich phase (normally β-Al3Mg2) is highly anodic with respect to the surrounding aluminum phase, thus is susceptible... alloys , and with varying amounts of debris scattered about the surface consistent with corrosion product, Figure 2b, that often forms over time within

Chemical kinetic functional sensitivity analysis: Elementary sensitivities

International Nuclear Information System (INIS)

Demiralp, M.; Rabitz, H.

1981-01-01

Sensitivity analysis is considered for kinetics problems defined in the space--time domain. This extends an earlier temporal Green's function method to handle calculations of elementary functional sensitivities deltau/sub i//deltaα/sub j/ where u/sub i/ is the ith species concentration and α/sub j/ is the jth system parameter. The system parameters include rate constants, diffusion coefficients, initial conditions, boundary conditions, or any other well-defined variables in the kinetic equations. These parameters are generally considered to be functions of position and/or time. Derivation of the governing equations for the sensitivities and the Green's funciton are presented. The physical interpretation of the Green's function and sensitivities is given along with a discussion of the relation of this work to earlier research

Repair of closely opposed cyclobutyl pyrimidine dimers in UV-sensitive human diploid fibroblasts

International Nuclear Information System (INIS)

Lam, L.H.; Reynolds, R.J.

1986-01-01

An enzyme-sensitive site assay has been used to examine the fate of closely opposed pyrimidine dimers in fibroblasts from individuals afflicted with various genetic disorders that confer increased cellular sensitivity to UV radiation. The disappearance of bifilar enzyme-sensitive sites was found to be normal in cells from individuals with Fanconi's anemia, Cockayne's syndrome, dyskeratosis congenita and the variant form of xeroderma pigmentosum. The rate of bifilar enzyme-sensitive site removal in XP cells assigned to complementation group C was reduced by an amount similar to that observed for the repair of isolated dimers. Our results indicate that the initiation of repair at closely opposed dimers is slow in XP-C cells but normal in all other cells examined. (Auth.)

Species-Specific Antimonial Sensitivity in Leishmania Is Driven by Post-Transcriptional Regulation of AQP1

Science.gov (United States)

Mandal, Goutam; Mandal, Srotoswati; Sharma, Mansi; Charret, Karen Santos; Papadopoulou, Barbara; Bhattacharjee, Hiranmoy; Mukhopadhyay, Rita

2015-01-01

Leishmania is a digenetic protozoan parasite causing leishmaniasis in humans. The different clinical forms of leishmaniasis are caused by more than twenty species of Leishmania that are transmitted by nearly thirty species of phlebotomine sand flies. Pentavalent antimonials (such as Pentostam or Glucantime) are the first line drugs for treating leishmaniasis. Recent studies suggest that pentavalent antimony (Sb(V)) acts as a pro-drug, which is converted to the more active trivalent form (Sb(III)). However, sensitivity to trivalent antimony varies among different Leishmania species. In general, Leishmania species causing cutaneous leishmaniasis (CL) are more sensitive to Sb(III) than the species responsible for visceral leishmaniasis (VL). Leishmania aquaglyceroporin (AQP1) facilitates the adventitious passage of antimonite down a concentration gradient. In this study, we show that Leishmania species causing CL accumulate more antimonite, and therefore exhibit higher sensitivity to antimonials, than the species responsible for VL. This species-specific differential sensitivity to antimonite is directly proportional to the expression levels of AQP1 mRNA. We show that the stability of AQP1 mRNA in different Leishmania species is regulated by their respective 3’-untranslated regions. The differential regulation of AQP1 mRNA explains the distinct antimonial sensitivity of each species. PMID:25714343

Application of PCT to the EBR II ceramic waste form

International Nuclear Information System (INIS)

Ebert, W. L.; Lewis, M. A.; Johnson, S. G.

2002-01-01

We are evaluating the use of the Product Consistency Test (PCT) developed to monitor the consistency of borosilicate glass waste forms for application to the multiphase ceramic waste form (CWF) that will be used to immobilize waste salts generated during the electrometallurgical conditioning of spent sodium-bonded nuclear fuel from the Experimental Breeder Reactor No. 2 (EBR II). The CWF is a multiphase waste form comprised of about 70% sodalite, 25% borosilicate glass binder, and small amounts of halite and oxide inclusions. It must be qualified for disposal as a non-standard high-level waste (HLW) form. One of the requirements in the DOE Waste Acceptance System Requirements Document (WASRD) for HLW waste forms is that the consistency of the waste forms be monitored.[1] Use of the PCT is being considered for the CWF because of the similarities of the dissolution behaviors of both the sodalite and glass binder phases in the CWF to borosilicate HLW glasses. This paper provides (1) a summary of the approach taken in selecting a consistency test for CWF production and (2) results of tests conducted to measure the precision and sensitivity of the PCT conducted with simulated CWF

Measuring sensitivity in pharmacoeconomic studies. Refining point sensitivity and range sensitivity by incorporating probability distributions.

Science.gov (United States)

Nuijten, M J

1999-07-01

The aim of the present study is to describe a refinement of a previously presented method, based on the concept of point sensitivity, to deal with uncertainty in economic studies. The original method was refined by the incorporation of probability distributions which allow a more accurate assessment of the level of uncertainty in the model. In addition, a bootstrap method was used to create a probability distribution for a fixed input variable based on a limited number of data points. The original method was limited in that the sensitivity measurement was based on a uniform distribution of the variables and that the overall sensitivity measure was based on a subjectively chosen range which excludes the impact of values outside the range on the overall sensitivity. The concepts of the refined method were illustrated using a Markov model of depression. The application of the refined method substantially changed the ranking of the most sensitive variables compared with the original method. The response rate became the most sensitive variable instead of the 'per diem' for hospitalisation. The refinement of the original method yields sensitivity outcomes, which greater reflect the real uncertainty in economic studies.

Variable screening and ranking using sampling-based sensitivity measures

International Nuclear Information System (INIS)

Wu, Y-T.; Mohanty, Sitakanta

2006-01-01

This paper presents a methodology for screening insignificant random variables and ranking significant important random variables using sensitivity measures including two cumulative distribution function (CDF)-based and two mean-response based measures. The methodology features (1) using random samples to compute sensitivities and (2) using acceptance limits, derived from the test-of-hypothesis, to classify significant and insignificant random variables. Because no approximation is needed in either the form of the performance functions or the type of continuous distribution functions representing input variables, the sampling-based approach can handle highly nonlinear functions with non-normal variables. The main characteristics and effectiveness of the sampling-based sensitivity measures are investigated using both simple and complex examples. Because the number of samples needed does not depend on the number of variables, the methodology appears to be particularly suitable for problems with large, complex models that have large numbers of random variables but relatively few numbers of significant random variables

Formability models for warm sheet metal forming analysis

Science.gov (United States)

Jiang, Sen

Several closed form models for the prediction of strain space sheet metal formability as a function of temperature and strain rate are proposed. The proposed models require only failure strain information from the uniaxial tension test at an elevated temperature setting and failure strain information from the traditionally defined strain space forming limit diagram at room temperature, thereby featuring the advantage of offering a full forming limit description without having to carry out expensive experimental studies for multiple modes of deformation under the elevated temperature. The Power law, Voce, and Johnson-Cook hardening models are considered along with the yield criterions of Hill's 48 and Logan-Hosford yield criteria. Acceptable correlations between the theory and experiment are reported for all the models under a plane strain condition. Among all the proposed models, the model featuring Johnson-Cook hardening model and Logan-Hosford yield behavior (LHJC model) was shown to best correlate with experiment. The sensitivity of the model with respect to various forming parameters is discussed. This work is significant to those aiming to incorporate closed-form formability models directly into numerical simulation programs for the purpose of design and analysis of products manufactured through the warm sheet metal forming process. An improvement based upon Swift's diffuse necking theory, is suggested in order to enhance the reliability of the model for biaxial stretch conditions. Theory relating to this improvement is provided in Appendix B.

The derivative based variance sensitivity analysis for the distribution parameters and its computation

International Nuclear Information System (INIS)

Wang, Pan; Lu, Zhenzhou; Ren, Bo; Cheng, Lei

2013-01-01

The output variance is an important measure for the performance of a structural system, and it is always influenced by the distribution parameters of inputs. In order to identify the influential distribution parameters and make it clear that how those distribution parameters influence the output variance, this work presents the derivative based variance sensitivity decomposition according to Sobol′s variance decomposition, and proposes the derivative based main and total sensitivity indices. By transforming the derivatives of various orders variance contributions into the form of expectation via kernel function, the proposed main and total sensitivity indices can be seen as the “by-product” of Sobol′s variance based sensitivity analysis without any additional output evaluation. Since Sobol′s variance based sensitivity indices have been computed efficiently by the sparse grid integration method, this work also employs the sparse grid integration method to compute the derivative based main and total sensitivity indices. Several examples are used to demonstrate the rationality of the proposed sensitivity indices and the accuracy of the applied method

CHEMICAL VAPOUR DEPOSITION FROM A RADIATION-SENSITIVE PRECURSOR

DEFF Research Database (Denmark)

2017-01-01

The present invention relates in one aspect to a method of depositing a thin film on a substrate by chemical vapour deposition (CVD) from a radiation-sensitive precursor substance. The method comprises the steps of: (i) placing the substrate in a reaction chamber of a CVD system; (ii) heating...... heating pulse followed by an idle period; (iii) during at least one of the idle periods, providing a pressure pulse of precursor substance inside the reaction chamber by feeding at least one precursor substance to the reaction chamber so as to establish a reaction partial pressure for thin film deposition...... is formed. According to a further aspect, the invention relates to a chemical vapour deposition (CVD) system for depositing a thin film onto a substrate using precursor substances containing at least one radiation sensitive species....

Ruthenium Sensitizers and Their Applications in Dye-Sensitized Solar Cells

Directory of Open Access Journals (Sweden)

Yuancheng Qin

2012-01-01

Full Text Available Dye-sensitized solar cells (DSSCs have attracted considerable attention in recent years due to the possibility of low-cost conversion of photovoltaic energy. The DSSCs-based ruthenium complexes as sensitizers show high efficiency and excellent stability, implying potential practical applications. This review focuses on recent advances in design and preparation of efficient ruthenium sensitizers and their applications in DSSCs, including thiocyanate ruthenium sensitizers and thiocyanate-free ruthenium sensitizers.

Initiation to radioactivity in third form of grammar schools

International Nuclear Information System (INIS)

Moulin, G.; Blanc, J.C.; Juste, G.

2001-01-01

The initiation to radioactivity can be aimed at adolescents to sensitive them to radiation field and to allow them to fabricate a pertinent opinion about the use of nuclear energy. The pupils of the third form of grammar school make a research on radioactivity and the different kind of radiations. The pupils participate to the measurement of the radiation emitted by the radon daughter and find the usual experimental protocol. (N.C.)

A comparative study of three cytotoxicity test methods for nanomaterials using sodium lauryl sulfate.

Science.gov (United States)

Kwon, Jae-Sung; Kim, Kwang-Mahn; Kim, Kyoung-Nam

2014-10-01

The biocompatibility evaluation of nanomaterials is essential for their medical diagnostic and therapeutic usage, where a cytotoxicity test is the simplest form of biocompatibility evaluation. Three methods have been commonly used in previous studies for the cytotoxicity testing of nanomaterials: trypan blue exclusion, colorimetric assay using water soluble tetrazolium (WST), and imaging under a microscope following calcein AM/ethidium homodimer-1 staining. However, there has yet to be a study to compare each method. Therefore, in this study three methods were compared using the standard reference material of sodium lauryl sulfate (SLS). Each method of the cytotoxicity test was carried out using mouse fibroblasts of L-929 exposed to different concentrations of SLS. Compared to the gold standard trypan blue exclusion test, both colorimetric assay using water soluble tetrazolium (WST) and imaging under microscope with calcein AM/ethidium homodimer-1 staining showed results that were not statistically different. Also, each method exhibited various advantages and disadvantages, which included the need of equipment, time taken for the experiment, and provision of additional information such as cell morphology. Therefore, this study concludes that all three methods of cytotoxicity testing may be valid, though careful consideration will be needed when selecting tests with regard to time, finances, and the amount of information required by the researcher(s).

Structural features of the KPI domain control APP dimerization, trafficking, and processing.

Science.gov (United States)

Ben Khalifa, Naouel; Tyteca, Donatienne; Marinangeli, Claudia; Depuydt, Mathieu; Collet, Jean-François; Courtoy, Pierre J; Renauld, Jean-Christophe; Constantinescu, Stefan; Octave, Jean-Noël; Kienlen-Campard, Pascal

2012-02-01

The two major isoforms of human APP, APP695 and APP751, differ by the presence of a Kunitz-type protease inhibitor (KPI) domain in the extracellular region. APP processing and function is thought to be regulated by homodimerization. We used bimolecular fluorescence complementation (BiFC) to study dimerization of different APP isoforms and mutants. APP751 was found to form significantly more homodimers than APP695. Mutation of dimerization motifs in the TM domain did not affect fluorescence complementation, but native folding of KPI is critical for APP751 homodimerization. APP751 and APP695 dimers were mostly localized at steady state in the Golgi region, suggesting that most of the APP751 and 695 dimers are in the secretory pathway. Mutation of the KPI led to the retention of the APP homodimers in the endoplasmic reticulum. We finally showed that APP751 is more efficiently processed through the nonamyloidogenic pathway than APP695. These findings provide new insight on the particular role of KPI domain in APP dimerization. The correlation observed between dimerization, subcellular localization, and processing suggests that dimerization acts as an efficient regulator of APP trafficking in the secretory compartments that has major consequences on its processing.

Dissociation between sensitization and learning-related neuromodulation in an aplysiid species.

Science.gov (United States)

Erixon, N J; Demartini, L J; Wright, W G

1999-06-14

Previous phylogenetic analyses of learning and memory in an opisthobranch lineage uncovered a correlation between two learning-related neuromodulatory traits and their associated behavioral phenotypes. In particular, serotonin-induced increases in sensory neuron spike duration and excitability, which are thought to underlie several facilitatory forms of learning in Aplysia, appear to have been lost over the course of evolution in a distantly related aplysiid, Dolabrifera dolabrifera. This deficit is paralleled by a behavioral deficit: individuals of Dolabrifera do not express generalized sensitization (reflex enhancement of an unhabituated response after a noxious stimulus is applied outside of the reflex receptive field) or dishabituation (reflex enhancement of a habituated reflex). The goal of the present study was to confirm and extend this correlation by testing for the neuromodulatory traits and generalized sensitization in an additional species, Phyllaplysia taylori, which is closely related to Dolabrifera. Instead, our results indicated a lack of correlation between the neuromodulatory and behavioral phenotypes. In particular, sensory neuron homologues in Phyllaplysia showed the ancestral neuromodulatory phenotype typified by Aplysia. Bath-applied 10 microM serotonin significantly increased homologue spike duration and excitability. However, when trained with the identical apparatus and protocols that produced generalized sensitization in Aplysia, individuals of Phyllaplysia showed no evidence of sensitization. Thus, this species expresses the neuromodulatory phenotype of its ancestors while appearing to express the behavioral phenotype of its near relative. These results suggests that generalized sensitization can be lost during the course of evolution in the absence of a deficit in these two neuromodulatory traits, and raises the possibility that the two traits may support some other form of behavioral plasticity in Phyllaplysia. The results also raise the

Biocidal Energetic Materials for the Destruction of Spore Forming Bacteria

Science.gov (United States)

2015-07-01

agent (GA). During a reaction the GA generates nucleation sites that promote the formation of bubbles. As the reaction wave passes, the gas pockets...studies have shown iodine producing reactive materials are effective against spore forming bacteria, but are sensitive to the relative humidity in the...testing environment. Results from tests run in relative high humidity environments show a decreased ability of iodine to effectively neutralize

Phase sensitive multichannel OCT

International Nuclear Information System (INIS)

Trasischker, W.

2015-01-01

The main aim of this thesis was to develop and improve phase sensitive, multichannel methods for optical coherence tomography (OCT) using light in the 840 nm and 1040 nm regime. Conventional OCT provides purely structural information by illuminating the sample by one beam and recording the backscattered signal with one detection channel. Combination of this approach with a raster scan enables the acquisition of 2D and 3D structural information with a resolution in the micrometer regime. However, sometimes additional image contrast or information is desired. Amongst other approaches, this can be provided by a phase sensitive analysis of the interference pattern. Combining phase sensitivity with the illumination of the sample by more than one beam and/or by recording the data using more than one data acquisition channel allows for even more enhanced imaging. While phase sensitive OCT gives access to additional contrast and information, multichannel OCT can provide higher imaging speed, scan eld size and exible dierential measurements. Amongst the dierential, phase sensitive approaches, Doppler OCT (DOCT) and polarization sensitive OCT (PS-OCT) are two of the most promising OCT modalities. While the former targets information on the movement of backscattering particles, the latter measures alterations of the polarization state of the light induced by the sample. Both techniques provide additional image contrast and are, due to the non-invasive and fast character of OCT, well suited for in vivo imaging of the human eye. In the course of this thesis, two dierent multichannel, phase sensitive OCT systems will be presented. First, a D-OCT system with three dierent sampling beams is described. With a central wavelength of 840 nm these three beams are emitted by three individual laser sources. This eectively eliminates any cross talk and provides the full depth range for each channel. Furthermore, by illuminating the sample from three dierent directions, the absolute

Moral sensitivity and moral distress in Iranian critical care nurses.

Science.gov (United States)

Borhani, Fariba; Abbaszadeh, Abbas; Mohamadi, Elham; Ghasemi, Erfan; Hoseinabad-Farahani, Mohammad Javad

2017-06-01

Moral sensitivity is the foremost prerequisite to ethical performance; a review of literature shows that nurses are sometimes not sensitive enough for a variety of reasons. Moral distress is a frequent phenomenon in nursing, which may result in paradoxes in care, dealing with patients and rendering high-quality care. This may, in turn, hinder the meeting of care objectives, thus affecting social healthcare standards. The present research was conducted to determine the relationship between moral sensitivity and moral distress of nurses in intensive care units. This study is a descriptive-correlation research. Lutzen's moral sensitivity questionnaire and Corley Moral Distress Questionnaire were used to gather data. Participants and research context: A total of 153 qualified nurses working in the hospitals affiliated to Shahid Beheshti University of Medical Sciences were selected for this study. Subjects were selected by census method. Ethical considerations: After explaining the objectives of the study, all the participants completed and signed the written consent form. To conduct the study, permission was obtained from the selected hospitals. Nurses' average moral sensitivity grade was 68.6 ± 7.8, which shows a moderate level of moral sensitivity. On the other hand, nurses also experienced a moderate level of moral distress (44.8 ± 16.6). Moreover, there was no meaningful statistical relationship between moral sensitivity and moral distress (p = 0.26). Although the nurses' moral sensitivity and moral distress were expected to be high in the intensive care units, it was moderate. This finding is consistent with the results of some studies and contradicts with others. As moral sensitivity is a crucial factor in care, it is suggested that necessary training be provided to develop moral sensitivity in nurses in education and practical environments. Furthermore, removing factors that contribute to moral distress may help decrease it in nurses.

The selectively bred high alcohol sensitivity (HAS) and low alcohol sensitivity (LAS) rats differ in sensitivity to nicotine.

Science.gov (United States)

de Fiebre, NancyEllen C; Dawson, Ralph; de Fiebre, Christopher M

2002-06-01

Studies in rodents selectively bred to differ in alcohol sensitivity have suggested that nicotine and ethanol sensitivities may cosegregate during selective breeding. This suggests that ethanol and nicotine sensitivities may in part be genetically correlated. Male and female high alcohol sensitivity (HAS), control alcohol sensitivity, and low alcohol sensitivity (LAS) rats were tested for nicotine-induced alterations in locomotor activity, body temperature, and seizure activity. Plasma and brain levels of nicotine and its primary metabolite, cotinine, were measured in these animals, as was the binding of [3H]cytisine, [3H]epibatidine, and [125I]alpha-bungarotoxin in eight brain regions. Both replicate HAS lines were more sensitive to nicotine-induced locomotor activity depression than the replicate LAS lines. No consistent HAS/LAS differences were seen on other measures of nicotine sensitivity; however, females were more susceptible to nicotine-induced seizures than males. No HAS/LAS differences in nicotine or cotinine levels were seen, nor were differences seen in the binding of nicotinic ligands. Females had higher levels of plasma cotinine and brain nicotine than males but had lower brain cotinine levels than males. Sensitivity to a specific action of nicotine cosegregates during selective breeding for differential sensitivity to a specific action of ethanol. The differential sensitivity of the HAS/LAS rats is due to differences in central nervous system sensitivity and not to pharmacokinetic differences. The differential central nervous system sensitivity cannot be explained by differences in the numbers of nicotinic receptors labeled in ligand-binding experiments. The apparent genetic correlation between ethanol and nicotine sensitivities suggests that common genes modulate, in part, the actions of both ethanol and nicotine and may explain the frequent coabuse of these agents.

Potential Roles of Amiloride-Sensitive Sodium Channels in Cancer Development

Directory of Open Access Journals (Sweden)

Siguang Xu

2016-01-01

Full Text Available The ENaC/degenerin ion channel superfamily includes the amiloride-sensitive epithelial sodium channel (ENaC and acid sensitive ionic channel (ASIC. ENaC is a multimeric ion channel formed by heteromultimeric membrane glycoproteins, which participate in a multitude of biological processes by mediating the transport of sodium (Na+ across epithelial tissues such as the kidney, lungs, bladder, and gut. Aberrant ENaC functions contribute to several human disease states including pseudohypoaldosteronism, Liddle syndrome, cystic fibrosis, and salt-sensitive hypertension. Increasing evidence suggests that ion channels not only regulate ion homeostasis and electric signaling in excitable cells but also play important roles in cancer cell behaviors such as proliferation, apoptosis, invasion, and migration. Indeed, ENaCs/ASICs had been reported to be associated with cancer characteristics. Given their cell surface localization and pharmacology, pharmacological strategies to target ENaC/ASIC family members may be promising cancer therapeutics.

Electrochemically Deposited Polypyrrole for Dye-Sensitized Solar Cell Counter Electrodes

Directory of Open Access Journals (Sweden)

Khamsone Keothongkham

2012-01-01

Full Text Available Polypyrrole films were coated on conductive glass by electrochemical deposition (alternative current or direct current process. They were then used as the dye-sensitized solar cell counter electrodes. Scanning electron microscopy revealed that polypyrrole forms a nanoparticle-like structure on the conductive glass. The amount of deposited polypyrrole (or film thickness increased with the deposition duration, and the performance of polypyrrole based-dye-sensitized solar cells is dependant upon polymer thickness. The highest efficiency of alternative current and direct current polypyrrole based-dye-sensitized solar cells (DSSCs is 4.72% and 4.02%, respectively. Electrochemical impedance spectroscopy suggests that the superior performance of alternative current polypyrrole solar cells is due to their lower charge-transfer resistance between counter electrode and electrolyte. The large charge-transfer resistance of direct current solar cells is attributed to the formation of unbounded polypyrrole chains minimizing the I3 − reduction rate.

GPCR Interaction: 157 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000907.2 ...

GPCR Interaction: 156 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available ation of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/...one receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expr...ents using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferas...ession of each receptor. 19896898 BRET NP_000697.1 ...

GPCR Interaction: 154 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR a...eceptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000045.1 ... ...using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

GPCR Interaction: 155 [GRIPDB[Archive

Lifescience Database Archive (English)

Full Text Available n of V1a, V2 and OT homodimers. In addition, coexpressions of different pairs of receptors (V1a/V2, V1a/OTR ...receptor to interact with another receptor) were identical whatever the pair of receptors coexpress...ed in the cells, which suggests that the proportion of homodimers and heterodimers depends on the relative expression of each receptor. 19896898 BRET NP_000907.2 ... ... using chimeric V1a or V2 vasopressin or oxytocin and receptors labeled on the C-terminus with luciferase or

Frequency tuning and directional sensitivity of tympanal vibrations in the field cricket Gryllus bimaculatus

DEFF Research Database (Denmark)

Lankheet, Martin J.; Cerkvenik, Uroš; Larsen, Ole Næsbye

2017-01-01

Female field crickets use phonotaxis to locate males by their calling song. Male song production and female behavioural sensitivity form a pair of matched frequency filters, which in Gryllus bimaculatus are tuned to a frequency of about 4.7 kHz. Directional sensitivity is supported by an elaborate...... play a major role in tuning directional sensitivity to the calling song frequency, by measuring tympanal vibrations as a function of sound direction and frequency. Rather than sharp frequency tuning of directional sensitivity corresponding to the calling song, we found broad frequency tuning......, with optima shifted to higher frequencies. These findings agree with predictions from a vector summation model for combining external and internal sounds. We show that the model provides robust directional sensitivity that is, however, broadly tuned with an optimum well above the calling song frequency. We...

Sensitivity Analysis of Dynamic Tariff Method for Congestion Management in Distribution Networks

DEFF Research Database (Denmark)

Huang, Shaojun; Wu, Qiuwei; Liu, Zhaoxi

2015-01-01

The dynamic tariff (DT) method is designed for the distribution system operator (DSO) to alleviate the congestions that might occur in a distribution network with high penetration of distribute energy resources (DERs). Sensitivity analysis of the DT method is crucial because of its decentralized...... control manner. The sensitivity analysis can obtain the changes of the optimal energy planning and thereby the line loading profiles over the infinitely small changes of parameters by differentiating the KKT conditions of the convex quadratic programming, over which the DT method is formed. Three case...

Procedures for Sensitive Immunoassay

Energy Technology Data Exchange (ETDEWEB)

Givol, D. [Department of Chemical Immunology, Weizmann Institute of Science, Rehovot (Israel)

1970-02-15

Sensitive immunoassay methods should be applied to small molecules of biological importance, which are non-immunogenic by themselves, such as small peptide hormones (e.g. bradykinin), plant hormones (e.g. indoleacetic acid), nucleotides and other small molecules. Methods of binding these small molecules, as haptens, to immunogenic carriers by various cross-linking agents are described (dicyclohexylcarbodiimide, tolylene-diisocyanate and glutaraldehyde), and the considerations involved in relation to the methods of binding and the specificity of the antibodies formed are discussed. Some uses of antibody bound to bromoacetyl cellulose as an immuno adsorbent convenient for assay of immunoglobulins are described. Finally, the sensitive immunoassay method of chemically modified phage is described. This includes methods of binding small molecules (such as the dinitrophenyl group, penicillin, indoleacetic acid) or proteins (such as insulin, immunoglobulins) to phages. Methods of direct chemical conjugation, or an indirect binding via anti-phage Fab, are described. The phage inactivation method by direct plating and its modifications (such as decision technique and complex inactivation) are compared with the more simple end-point titration method. The inhibition of phage inactivation has some advantages as it does not require radioactive material, or expensive radioactive counters, and avoids the need for separation between bound and unbound antigen. Hence, if developed, it could be used as an alternative to radioimmunoassay. (author)

Contributions to sensitivity analysis and generalized discriminant analysis

International Nuclear Information System (INIS)

Jacques, J.

2005-12-01

Two topics are studied in this thesis: sensitivity analysis and generalized discriminant analysis. Global sensitivity analysis of a mathematical model studies how the output variables of this last react to variations of its inputs. The methods based on the study of the variance quantify the part of variance of the response of the model due to each input variable and each subset of input variables. The first subject of this thesis is the impact of a model uncertainty on results of a sensitivity analysis. Two particular forms of uncertainty are studied: that due to a change of the model of reference, and that due to the use of a simplified model with the place of the model of reference. A second problem was studied during this thesis, that of models with correlated inputs. Indeed, classical sensitivity indices not having significance (from an interpretation point of view) in the presence of correlation of the inputs, we propose a multidimensional approach consisting in expressing the sensitivity of the output of the model to groups of correlated variables. Applications in the field of nuclear engineering illustrate this work. Generalized discriminant analysis consists in classifying the individuals of a test sample in groups, by using information contained in a training sample, when these two samples do not come from the same population. This work extends existing methods in a Gaussian context to the case of binary data. An application in public health illustrates the utility of generalized discrimination models thus defined. (author)

Developpement of a photoaffinity probe for the sensitive detection of matrix metallo-protease active forms from complex biological systems

International Nuclear Information System (INIS)

Nury, Catherine

2012-01-01

A new activity-based probe able to covalently modify the active site of proteases belonging to the matrix metallo-protease family (MMPs) has been developed in this thesis project. The probe was shown to behave as potent inhibitor of several MMPs, with nanomolar Ki values. This probe was also able to modify specifically only the free active site of MMPs, with particular high yields of cross-linking varying from 50 % to 11 %, depending of the MMPs tested. Using radioactivity as means of detection, this probe was able to detect active form of MMPs with a threshold of 1 femto-mole. Applied to the study of bronchoalveolar fluids (BAL) from mice exposed to nanoparticles by a lung aspiration protocol, this probe revealed the presence of the catalytic domain of MMP-12 under its active form, but not in control animals. When used to detect active form of MMPs from extracts obtained from human arteries of patient suffering from atherosclerosis, the probe was not able to detect such MMP active forms. Despite this negative result, the detection of active form of MMP in pathological fluid like BAL has never been reported before this work. Having validated this novel MMP activity-based probe, it will be possible to use it now for detecting MMPs from other pathological fluids or tissues extracts in which MMPs can be good markers of the pathology. (author) [fr

SENSIT: a cross-section and design sensitivity and uncertainty analysis code

International Nuclear Information System (INIS)

Gerstl, S.A.W.

1980-01-01

SENSIT computes the sensitivity and uncertainty of a calculated integral response (such as a dose rate) due to input cross sections and their uncertainties. Sensitivity profiles are computed for neutron and gamma-ray reaction cross sections of standard multigroup cross section sets and for secondary energy distributions (SEDs) of multigroup scattering matrices. In the design sensitivity mode, SENSIT computes changes in an integral response due to design changes and gives the appropriate sensitivity coefficients. Cross section uncertainty analyses are performed for three types of input data uncertainties: cross-section covariance matrices for pairs of multigroup reaction cross sections, spectral shape uncertainty parameters for secondary energy distributions (integral SED uncertainties), and covariance matrices for energy-dependent response functions. For all three types of data uncertainties SENSIT computes the resulting variance and estimated standard deviation in an integral response of interest, on the basis of generalized perturbation theory. SENSIT attempts to be more comprehensive than earlier sensitivity analysis codes, such as SWANLAKE

A flow cytometry-based assay for quantifying non-plaque forming strains of yellow fever virus.

Directory of Open Access Journals (Sweden)

Erika Hammarlund

Full Text Available Primary clinical isolates of yellow fever virus can be difficult to quantitate by standard in vitro methods because they may not form discernable plaques or induce a measurable cytopathic effect (CPE on cell monolayers. In our hands, the Dakar strain of yellow fever virus (YFV-Dakar could not be measured by plaque assay (PA, focus-forming assay (FFA, or by measurement of CPE. For these reasons, we developed a YFV-specific monoclonal antibody (3A8.B6 and used it to optimize a highly sensitive flow cytometry-based tissue culture limiting dilution assay (TC-LDA to measure levels of infectious virus. The TC-LDA was performed by incubating serial dilutions of virus in replicate wells of C6/36 cells and stained intracellularly for virus with MAb 3A8.B6. Using this approach, we could reproducibly quantitate YFV-Dakar in tissue culture supernatants as well as from the serum of viremic rhesus macaques experimentally infected with YFV-Dakar. Moreover, the TC-LDA approach was >10-fold more sensitive than standard plaque assay for quantitating typical plaque-forming strains of YFV including YFV-17D and YFV-FNV (French neurotropic vaccine. Together, these results indicate that the TC-LDA technique is effective for quantitating both plaque-forming and non-plaque-forming strains of yellow fever virus, and this methodology may be readily adapted for the study and quantitation of other non-plaque-forming viruses.

Sensitivity analysis for decision-making using the MORE method-A Pareto approach

International Nuclear Information System (INIS)

Ravalico, Jakin K.; Maier, Holger R.; Dandy, Graeme C.

2009-01-01

Integrated Assessment Modelling (IAM) incorporates knowledge from different disciplines to provide an overarching assessment of the impact of different management decisions. The complex nature of these models, which often include non-linearities and feedback loops, requires special attention for sensitivity analysis. This is especially true when the models are used to form the basis of management decisions, where it is important to assess how sensitive the decisions being made are to changes in model parameters. This research proposes an extension to the Management Option Rank Equivalence (MORE) method of sensitivity analysis; a new method of sensitivity analysis developed specifically for use in IAM and decision-making. The extension proposes using a multi-objective Pareto optimal search to locate minimum combined parameter changes that result in a change in the preferred management option. It is demonstrated through a case study of the Namoi River, where results show that the extension to MORE is able to provide sensitivity information for individual parameters that takes into account simultaneous variations in all parameters. Furthermore, the increased sensitivities to individual parameters that are discovered when joint parameter variation is taken into account shows the importance of ensuring that any sensitivity analysis accounts for these changes.

A sensitivity analysis on the springback behavior of the Unconstrained Bending Problem

NARCIS (Netherlands)

Meinders, Vincent T.; Konter, A.W.A.; Meijers, S.E.; Atzema, E.H.; Kappert, H.

2006-01-01

Sheet metal forming software is commonly used in the automotive and sheet metal sectors to support the design stage. However, the ability of the currently available software to accurately predict springback is limited. A sensitivity analysis of the springback behavior of a simple product is

Environment-sensitive behavior of fluorescent molecular rotors

Directory of Open Access Journals (Sweden)

Theodorakis Emmanuel A

2010-09-01

Full Text Available Abstract Molecular rotors are a group of fluorescent molecules that form twisted intramolecular charge transfer (TICT states upon photoexcitation. When intramolecular twisting occurs, the molecular rotor returns to the ground state either by emission of a red-shifted emission band or by nonradiative relaxation. The emission properties are strongly solvent-dependent, and the solvent viscosity is the primary determinant of the fluorescent quantum yield from the planar (non-twisted conformation. This viscosity-sensitive behavior gives rise to applications in, for example, fluid mechanics, polymer chemistry, cell physiology, and the food sciences. However, the relationship between bulk viscosity and the molecular-scale interaction of a molecular rotor with its environment are not fully understood. This review presents the pertinent theories of the rotor-solvent interaction on the molecular level and how this interaction leads to the viscosity-sensitive behavior. Furthermore, current applications of molecular rotors as microviscosity sensors are reviewed, and engineering aspects are presented on how measurement accuracy and precision can be improved.

In situ detection of estrogen receptor dimers in breast carcinoma cells in archival materials using proximity ligation assay (PLA).

Science.gov (United States)

Iwabuchi, Erina; Miki, Yasuhiro; Ono, Katsuhiko; Onodera, Yoshiaki; Suzuki, Takashi; Hirakawa, Hisashi; Ishida, Takanori; Ohuchi, Noriaki; Sasano, Hironobu

2017-01-01

Estrogen receptor (ER) is required for carcinoma cell proliferation in the great majority of breast cancer and also functions as a dimer. ER dimeric proteins have been largely identified by BRET/FRET analyses but their in situ visualization have not yet been reported. Recently, in situ Proximity Ligation Assay (PLA) has been developed as the methods detecting protein interactions in situ. Therefore, in this study we firstly demonstrated the dimerization of ERα in breast carcinoma cell lines and tissues using PLA. The human breast carcinoma cell lines MCF-7, T-47D and MDA-MB-231 were used in this study. Cells were treated with ER agonist or antagonist and fixed in 4% PFA, and ER dimers were subsequently detected using PLA. The evaluation of ER dimers in breast carcinoma cell lines were quantified by measuring the area of dots localized in the nuclei using image analysis. We also firstly demonstrated the visualization of ER dimer patterns in 10% formalin-fixed paraffin-embedded tissues of breast cancer using PLA technique. Estradiol (E2) administration induced ERα homodimers in the nuclei of MCF-7 and T-47D but not in ER-negative MDA-MB-231. 4-OH tamoxifen also induced ERα homodimers but the subcellular localization of these ERα homodimers was predominant in cytoplasm instead of the nuclei induced by E2 treatment. ICI182,780 treatment did decrease the number of formation of ERα homodimers in MCF-7. In breast cancer patients, ERα PLA score was significantly correlated positively with ERα- or PgR (progesterone receptor) immunohistochemical scores and inversely with Ki-67-labeling index, respectively. We also demonstrated the ERα/β heterodimer as well as ERα homodimers in both breast carcinoma cell lines and surgical pathology specimens. In summary, we did firstly succeed in the visualization of ER dimeric proteins using PLA method. The evaluation of ER dimer patterns could provide pivotal information as to the prediction of response to endocrine therapy of

Context Sensitive Modeling of Cancer Drug Sensitivity.

Directory of Open Access Journals (Sweden)

Bo-Juen Chen

Full Text Available Recent screening of drug sensitivity in large panels of cancer cell lines provides a valuable resource towards developing algorithms that predict drug response. Since more samples provide increased statistical power, most approaches to prediction of drug sensitivity pool multiple cancer types together without distinction. However, pan-cancer results can be misleading due to the confounding effects of tissues or cancer subtypes. On the other hand, independent analysis for each cancer-type is hampered by small sample size. To balance this trade-off, we present CHER (Contextual Heterogeneity Enabled Regression, an algorithm that builds predictive models for drug sensitivity by selecting predictive genomic features and deciding which ones should-and should not-be shared across different cancers, tissues and drugs. CHER provides significantly more accurate models of drug sensitivity than comparable elastic-net-based models. Moreover, CHER provides better insight into the underlying biological processes by finding a sparse set of shared and type-specific genomic features.

Dimerization and DNA-binding of ASR1, a small hydrophilic protein abundant in plant tissues suffering from water loss

International Nuclear Information System (INIS)

Maskin, Laura; Frankel, Nicolas; Gudesblat, Gustavo; Demergasso, Maria J.; Pietrasanta, Lia I.; Iusem, Norberto D.

2007-01-01

The Asr gene family is present in Spermatophyta. Its members are generally activated under water stress. We present evidence that tomato ASR1, one of the proteins of the family, accumulates in seed during late stages of embryogenesis, a physiological process characterized by water loss. In vitro, electrophoretic assays show a homo-dimeric structure for ASR1 and highlight strong non-covalent interactions between monomers prone to self-assemble. Direct visualization of single molecules by atomic force microscopy (AFM) confirms that ASR1 forms homodimers and that uncovers both monomers and dimers bind double stranded DNA

Biochemical characterization of the small hydrophobic protein of avian metapneumovirus.

Science.gov (United States)

Deng, Qiji; Song, Minxun; Demers, Andrew; Weng, Yuejin; Lu, Wuxun; Wang, Dan; Kaushik, Radhey S; Yu, Qingzhong; Li, Feng

2012-08-01

Avian metapneumovirus (AMPV) is a paramyxovirus that has three membrane proteins (G, F, and SH). Among them, the SH protein is a small type II integral membrane protein that is incorporated into virions and is only present in certain paramyxoviruses. In the present study, we show that the AMPV SH protein is modified by N-linked glycans and can be released into the extracellular environment. Furthermore, we demonstrate that glycosylated AMPV SH proteins form homodimers through cysteine-mediated disulfide bonds, which has not been reported previously for SH proteins of paramyxoviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

Crystal structure of enolase from Drosophila melanogaster.

Science.gov (United States)

Sun, Congcong; Xu, Baokui; Liu, Xueyan; Zhang, Zhen; Su, Zhongliang

2017-04-01

Enolase is an important enzyme in glycolysis and various biological processes. Its dysfunction is closely associated with diseases. Here, the enolase from Drosophila melanogaster (DmENO) was purified and crystallized. A crystal of DmENO diffracted to 2.0 Å resolution and belonged to space group R32. The structure was solved by molecular replacement. Like most enolases, DmENO forms a homodimer with conserved residues in the dimer interface. DmENO possesses an open conformation in this structure and contains conserved elements for catalytic activity. This work provides a structural basis for further functional and evolutionary studies of enolase.

Comparative assessment of recombinant and native immunogenic forms of Fasciola hepatica proteins for serodiagnosis of sheep fasciolosis.

Science.gov (United States)

Mokhtarian, Kobra; Meamar, Ahmad Reza; Khoshmirsafa, Majid; Razmjou, Elham; Masoori, Leila; Khanmohammadi, Majid; Akhlaghi, Lame; Falak, Reza

2018-01-01

Laboratory diagnosis of sheep fasciolosis is commonly performed by coprological examinations; however, this method may lead to false negative results during the acute phase of the infection. Furthermore, the poor sensitivity of coprological methods is considered to be a paradox in the chronic phase of the infection. In this study, we compared the immunoreactivity of native and recombinant forms of Fasciola hepatica excretory/secretory antigens and determined their capabilities for the development of F. hepatica-specific immunoassays. Immunoreactivity and specificity of recombinant and native forms of F. hepatica antigens, including fatty acid binding protein (FABP), glutathione-S-transferase (GST), and cathepsin L-1 (CL1), in parallel with native forms of FABP and GST, were studied for serodiagnosis of the chronic form of sheep fasciolosis, individually or in combination with each other by enzyme-linked immunosorbent assays (ELISA). The correlation of the findings was assessed by receiver-operator characteristic (ROC); furthermore, the specificity and sensitivity were assessed by Youden's J. Serologic cross-reactivity was evaluated using samples from healthy sheep (n = 40), Fasciola-infected sheep (n = 30), and sheep with other parasitic infections (n = 43). The FABPs were determined to be greater than 95% sensitive for F. hepatica serodiagnosis. The most desirable diagnostic recombinant antigen was rCL1, which showed 100% sensitivity and 97% specificity in ELISA and was capable of discriminating the positive and negative samples by maximum Youden's J results. We conclude that rCL1 can be used for routine serodiagnosis of chronic fasciolosis. Thus, it could be advantageous in development of immunoassays for screening of ovine herds in fasciolosis-endemic areas and as a reliable agent for detection of fasciolosis in non-endemic regions.

Synaptic Mechanisms of Induction and Maintenance of Long-Term Sensitization Memory in Aplysia

OpenAIRE

Glanzman, DL

2013-01-01

The marine snail Aplysia californica exhibits a simple defensive withdrawal reflex that can undergo several forms of learning. In particular, the reflex can exhibit long-term sensitization (LTS), a form of nonassociative memory. LTS is mediated by long-term facilitation (LTF) of the monosynaptic connection between the sensory and motor neurons that mediate the withdrawal reflex. LTS and LTF represent one of the best understood model systems of long-term memory extent. Furthermore, discoveries...

Radiogenic male breast cancer with in vitro sensitivity to ionizing radiation and bleomycin

International Nuclear Information System (INIS)

Greene, M.H.; Goedert, J.J.; Bech-Hansen, N.T.; McGuire, D.; Paterson, M.C.; Fraumeni, J.F. Jr.

1983-01-01

A cytogenetically normal man with gynecomastia and a family history of diverse cancers developed adenocarcinoma of the breast 30 years following thymic irradiation. In vitro experiments measuring colony-forming ability of cultured skin fibroblasts from family members implied that the patient had a small but significant increase in sensitivity to ionizing radiation, and a moderate increase in sensitivity to bleomycin, a radiomimetic drug. Enhanced radiosensitivity of fibroblasts from the patient's mother, and bleomycin sensitivity of fibroblasts from the sister suggested, but did not prove, that genetic susceptibility affected the risk of radiogenic cancer in this individual. In vitro studies of cancer-prone kindreds are a useful research strategy in delineating mechanisms of carcinogenesis

Effects of compositional modifications on the sensitization behavior of Fe-Cr-Mn steels

International Nuclear Information System (INIS)

Edgemon, G.L.; Tortorelli, P.F.; Bell, G.E.C.

1992-01-01

Fe-Cr-Mn steels may possibly be used in conjuction with aqueous blankets or coolants in a fusion device. Therefore, standard chemical immersion (modified Strauss) tests were conducted to characterize the effects of compositional modifications on the thermal sensitization behavior of these steels. A good correlation among weight losses, intergranular corrosion, and cracking was found. The most effective means of decreasing their susceptibility was through reduction of the carbon concentration of these steels to 0.1%, but the sensitization resistance of Fe-Cr-Mn-0.1 C compositions was still inferior to type 304L and other similar stainless steels. Alloying additions that form stable carbides did not have a very significant influence on the sensitization behavior. (orig.)

Harmonic Maass forms and mock modular forms

CERN Document Server

Bringmann, Kathrin; Ono, Ken

2017-01-01

Modular forms and Jacobi forms play a central role in many areas of mathematics. Over the last 10-15 years, this theory has been extended to certain non-holomorphic functions, the so-called "harmonic Maass forms". The first glimpses of this theory appeared in Ramanujan's enigmatic last letter to G. H. Hardy written from his deathbed. Ramanujan discovered functions he called "mock theta functions" which over eighty years later were recognized as pieces of harmonic Maass forms. This book contains the essential features of the theory of harmonic Maass forms and mock modular forms, together with a wide variety of applications to algebraic number theory, combinatorics, elliptic curves, mathematical physics, quantum modular forms, and representation theory.

Validation of a patient-centered culturally sensitive health care office staff inventory.

Science.gov (United States)

Tucker, Carolyn M; Wall, Whitney; Marsiske, Michael; Nghiem, Khanh; Roncoroni, Julia

2015-09-01

Research suggests that patient-perceived culturally sensitive health care encompasses multiple components of the health care delivery system including the cultural sensitivity of front desk office staff. Despite this, research on culturally sensitive health care focuses almost exclusively on provider behaviors, attitudes, and knowledge. This is due in part to the paucity of instruments available to assess the cultural sensitivity of front desk office staff. Thus, the objective of the present study is to determine the psychometric properties of the pilot Tucker-Culturally Sensitive Health Care Office Staff Inventory-Patient Form (T-CSHCOSI-PF), which is an instrument designed to enable patients to evaluate the patient-defined cultural sensitivity of their front desk office staff. A sample of 1648 adult patients was recruited by staff at 67 health care sites across the United States. These patients anonymously completed the T-CSHCOSI-PF, a demographic data questionnaire, and a patient satisfaction questionnaire. Findings Confirmatory factor analyses of the TCSHCOSI-PF revealed that this inventory has two factors with high internal consistency reliability and validity (Cronbach's αs=0.97 and 0.95). It is concluded that the T-CSHCOSI-PF is a psychometrically strong and useful inventory for assessing the cultural sensitivity of front desk office staff. This inventory can be used to support culturally sensitive health care research, evaluate the job performance of front desk office staff, and aid in the development of trainings designed to improve the cultural sensitivity of these office staff.

A sensitivity-enhanced refractive index sensor using a single-mode thin-core fiber incorporating an abrupt taper.

Science.gov (United States)

Shi, Jie; Xiao, Shilin; Yi, Lilin; Bi, Meihua

2012-01-01

A sensitivity-enhanced fiber-optic refractive index (RI) sensor based on a tapered single-mode thin-core diameter fiber is proposed and experimentally demonstrated. The sensor head is formed by splicing a section of tapered thin-core diameter fiber (TCF) between two sections of single-mode fibers (SMFs). The cladding modes are excited at the first SMF-TCF interface, and then interfere with the core mode at the second interface, thus forming an inter-modal interferometer (IMI). An abrupt taper (tens of micrometers long) made by the electric-arc-heating method is utilized, and plays an important role in improving sensing sensitivity. The whole manufacture process only involves fiber splicing and tapering, and all the fabrication process can be achieved by a commercial fiber fusion splicer. Using glycerol and water mixture solution as an example, the experimental results show that the refractive index sensitivity is measured to be 0.591 nm for 1% change of surrounding RI. The proposed sensor structure features simple structure, low cost, easy fabrication, and high sensitivity.

A Sensitivity-Enhanced Refractive Index Sensor Using a Single-Mode Thin-Core Fiber Incorporating an Abrupt Taper

Directory of Open Access Journals (Sweden)

Jie Shi

2012-04-01

Full Text Available A sensitivity-enhanced fiber-optic refractive index (RI sensor based on a tapered single-mode thin-core diameter fiber is proposed and experimentally demonstrated. The sensor head is formed by splicing a section of tapered thin-core diameter fiber (TCF between two sections of single-mode fibers (SMFs. The cladding modes are excited at the first SMF-TCF interface, and then interfere with the core mode at the second interface, thus forming an inter-modal interferometer (IMI. An abrupt taper (tens of micrometers long made by the electric-arc-heating method is utilized, and plays an important role in improving sensing sensitivity. The whole manufacture process only involves fiber splicing and tapering, and all the fabrication process can be achieved by a commercial fiber fusion splicer. Using glycerol and water mixture solution as an example, the experimental results show that the refractive index sensitivity is measured to be 0.591 nm for 1% change of surrounding RI. The proposed sensor structure features simple structure, low cost, easy fabrication, and high sensitivity.

Weight gain following treatment of hyperthyroidism.

Science.gov (United States)

Dale, J; Daykin, J; Holder, R; Sheppard, M C; Franklyn, J A

2001-08-01

Patients frequently express concern that treating hyperthyroidism will lead to excessive weight gain. This study aimed to determine the extent of, and risk factors for, weight gain in an unselected group of hyperthyroid patients. We investigated 162 consecutive hyperthyroid patients followed for at least 6 months. Height, weight, clinical features, biochemistry and management were recorded at each clinic visit. Documented weight gain was 5.42 +/- 0.46 kg (mean +/- SE) and increase in BMI was 8.49 +/- 0.71%, over a mean 24.2 +/- 1.6 months. Pre-existing obesity, Graves' disease causing hyperthyroidism, weight loss before presentation and length of follow-up each independently predicted weight gain. Patients treated with thionamides or radioiodine gained a similar amount of weight (thionamides, n = 87, 5.16 +/- 0.63 kg vs. radioiodine, n = 62, 4.75 +/- 0.57 kg, P = 0.645), but patients who underwent thyroidectomy (n = 13) gained more weight (10.27 +/- 2.56 kg vs. others, P = 0.007). Development of hypothyroidism (even transiently) was associated with weight gain (never hypothyroid, n = 102, 4.57 +/- 0.52 kg, transiently hypothyroid, n = 29, 5.37 +/- 0.85 kg, on T4, n = 31, 8.06 +/- 1.42 kg, P = 0.014). This difference remained after correcting for length of follow-up. In the whole cohort, weight increased by 3.95 +/- 0.40 kg at 1 year (n = 144) to 9.91 +/- 1.62 kg after 4 years (n = 27) (P = 0.008), representing a mean weight gain of 3.66 +/- 0.44 kg/year. We have demonstrated marked weight gain after treatment of hyperthyroidism. Pre-existing obesity, a diagnosis of Graves' disease and prior weight loss independently predicted weight gain and weight continued to rise with time. Patients who became hypothyroid, despite T4 replacement, gained most weight.

Improving the sensitivity of LISA

International Nuclear Information System (INIS)

Nayak, K Rajesh; Pai, A; Dhurandhar, S V; Vinet, J-Y

2003-01-01

It has been shown in several recent papers that the six Doppler data streams obtained from a triangular LISA configuration can be combined by appropriately delaying the data streams for cancelling the laser frequency noise. Raw laser noise is several orders of magnitude above the other noises and thus it is essential to bring it down to the level of other noises such as shot, acceleration, etc. A rigorous and systematic formalism using the powerful techniques of computational commutative algebra was developed, which generates in principle all the data combinations cancelling the laser frequency noise. The relevant data combinations form a first module of syzygies. In this paper, we use this formalism to advantage for optimizing the sensitivity of LISA by analysing the noise and signal covariance matrices. The signal covariance matrix is calculated for binaries whose frequency changes at most adiabatically and the signal is averaged over polarizations and directions. We then present the extremal SNR curves for all the data combinations in the module. They correspond to the eigenvectors of the noise and signal covariance matrices. A LISA 'network' SNR is also computed by combining the outputs of the eigenvectors. We show that substantial gains in sensitivity can be obtained by employing these strategies. The maximum SNR curve can yield an improvement up to 70% over the Michelson, mainly at high frequencies, while the improvement using the network SNR ranges from 40% to over 100%. Finally, we describe a simple toy model, in which LISA rotates in a plane. In this analysis, we estimate the improvement in the LISA sensitivity, if one switches from one data combination to another as it rotates. Here the improvement in sensitivity, if one switches optimally over three cyclic data combinations of the eigenvector, is about 55% on average over the LISA bandwidth. The corresponding SNR improvement increases to 60%, if one maximizes over the module

Bioaccumulation and chemical forms of cadmium, copper and lead in aquatic plants

Directory of Open Access Journals (Sweden)

JinZhao Hu

2010-02-01

Full Text Available The cadmium(Cd, copper(Cu and lead(Pb accumulation, as well as their relative content of different chemical forms in Sagittaria sagittifolia L. and Potamogeton crispus L. were determined. The results showed that both the plants had the ability to accumulate large amounts of Cd, Cu and Pb, and they absorbed metals in dose-dependent manners. The roots of S. sagittifolia appeared more sensitive to Cd and Pb than the leaves of P. crispus. The potential of Cu uptake by these two plant tissues was similar. Under the same concentration, the uptake of Cu for both the plants was higher than Pb and Cd, while that of Pb was lowest. The Cd, Cu and Pb existed with various forms in the plants. Cd and Pb were mainly in the NaCl extractable form in S. sagittifolia and P. crispus. The HAc and ethanol extractable Cu were the main forms in the root, whereas the ethanol extractable form was the dominant chemical form in the caulis and bulb of the S. sagittifolia L.

Analysis and Compensation for Gear Accuracy with Setting Error in Form Grinding

Directory of Open Access Journals (Sweden)

Chenggang Fang

2015-01-01

Full Text Available In the process of form grinding, gear setting error was the main factor that influenced the form grinding accuracy; we proposed an effective method to improve form grinding accuracy that corrected the error by controlling the machine operations. Based on establishing the geometry model of form grinding and representing the gear setting errors as homogeneous coordinate, tooth mathematic model was obtained and simplified under the gear setting error. Then, according to the gear standard of ISO1328-1: 1997 and the ANSI/AGMA 2015-1-A01: 2002, the relationship was investigated by changing the gear setting errors with respect to tooth profile deviation, helix deviation, and cumulative pitch deviation, respectively, under the condition of gear eccentricity error, gear inclination error, and gear resultant error. An error compensation method was proposed based on solving sensitivity coefficient matrix of setting error in a five-axis CNC form grinding machine; simulation and experimental results demonstrated that the method can effectively correct the gear setting error, as well as further improving the forming grinding accuracy.

Liking, Wanting and the Incentive-Sensitization Theory of Addiction

Science.gov (United States)

Berridge, Kent C.; Robinson, Terry E.

2016-01-01

Rewards are both ‘liked’ and ‘wanted’, and those two words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of ‘wanting’ a particular reward is dissociable from circuitry that mediates the degree to which it is ‘liked’. Incentive salience or ‘wanting’, a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, ‘liking’, or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological ‘wanting’, especially triggered by cues, without necessarily an amplification of ‘liking’. This is due to long-lasting changes in dopamine-related motivation systems of susceptible individuals, called neural sensitization. A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. PMID:27977239

Liking, wanting, and the incentive-sensitization theory of addiction.

Science.gov (United States)

Berridge, Kent C; Robinson, Terry E

2016-11-01

Rewards are both "liked" and "wanted," and those 2 words seem almost interchangeable. However, the brain circuitry that mediates the psychological process of "wanting" a particular reward is dissociable from circuitry that mediates the degree to which it is "liked." Incentive salience or "wanting," a form of motivation, is generated by large and robust neural systems that include mesolimbic dopamine. By comparison, "liking," or the actual pleasurable impact of reward consumption, is mediated by smaller and fragile neural systems, and is not dependent on dopamine. The incentive-sensitization theory posits the essence of drug addiction to be excessive amplification specifically of psychological "wanting," especially triggered by cues, without necessarily an amplification of "liking." This is because of long-lasting changes in dopamine-related motivation systems of susceptible individuals, called "neural sensitization." A quarter-century after its proposal, evidence has continued to grow in support the incentive-sensitization theory. Further, its scope is now expanding to include diverse behavioral addictions and other psychopathologies. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Highly sensitive assay for tyrosine hydroxylase activity by high-performance liquid chromatography.

Science.gov (United States)

Nagatsu, T; Oka, K; Kato, T

1979-07-21

A highly sensitive assay for tyrosine hydroxylase (TH) activity by high-performance liquid chromatography (HPLC) with amperometric detection was devised based on the rapid isolation of enzymatically formed DOPA by a double-column procedure, the columns fitted together sequentially (the top column of Amberlite CG-50 and the bottom column of aluminium oxide). DOPA was adsorbed on the second aluminium oxide column, then eluted with 0.5 M hydrochloric acid, and assayed by HPLC with amperometric detection. D-Tyrosine was used for the control. alpha-Methyldopa was added to the incubation mixture as an internal standard after incubation. This assay was more sensitive than radioassays and 5 pmol of DOPA formed enzymatically could be measured in the presence of saturating concentrations of tyrosine and 6-methyltetrahydropterin. The TH activity in 2 mg of human putamen could be easily measured, and this method was found to be particularly suitable for the assay of TH activity in a small number of nuclei from animal and human brain.

Development of sandwich-form biosensor to detect Mycobacterium tuberculosis complex in clinical sputum specimens.

Science.gov (United States)

Shojaei, Taha Roodbar; Mohd Salleh, Mohamad Amran; Tabatabaei, Meisam; Ekrami, Alireza; Motallebi, Roya; Rahmani-Cherati, Tavoos; Hajalilou, Abdollah; Jorfi, Raheleh

2014-01-01

Mycobacterium tuberculosis, the causing agent of tuberculosis, comes second only after HIV on the list of infectious agents slaughtering many worldwide. Due to the limitations behind the conventional detection methods, it is therefore critical to develop new sensitive sensing systems capable of quick detection of the infectious agent. In the present study, the surface modified cadmium-telluride quantum dots and gold nanoparticles conjunct with two specific oligonucleotides against early secretory antigenic target 6 were used to develop a sandwich-form fluorescence resonance energy transfer-based biosensor to detect M. tuberculosis complex and differentiate M. tuberculosis and M. bovis Bacille Calmette-Guerin simultaneously. The sensitivity and specificity of the newly developed biosensor were 94.2% and 86.6%, respectively, while the sensitivity and specificity of polymerase chain reaction and nested polymerase chain reaction were considerably lower, 74.2%, 73.3% and 82.8%, 80%, respectively. The detection limits of the sandwich-form fluorescence resonance energy transfer-based biosensor were far lower (10 fg) than those of the polymerase chain reaction and nested polymerase chain reaction (100 fg). Although the cost of the developed nanobiosensor was slightly higher than those of the polymerase chain reaction-based techniques, its unique advantages in terms of turnaround time, higher sensitivity and specificity, as well as a 10-fold lower detection limit would clearly recommend this test as a more appropriate and cost-effective tool for large scale operations. Copyright © 2014 Elsevier Editora Ltda. All rights reserved.

Forming limit and fracture mechanism of ferritic stainless steel sheets

International Nuclear Information System (INIS)

Xu Le; Barlat, Frederic; Ahn, Deok Chan; Bressan, Jose Divo

2011-01-01

Research highlights: → Forming limit curves of two ferritic stainless steel sheets were well predicted. → Failure occurs by necking in uniaxial and plane strain tension for both materials. → Failure occurs by shearing in balanced biaxial tension for both materials. → Strain rate sensitivity does not affect the limit strains a lot for both materials. → Strain rate sensitivity likely influences the failure mode for both materials. - Abstract: In this work, the forming limit curves (FLCs) of two ferritic stainless steel sheets, AISI409L and AISI430, were predicted with the Marciniak-Kuczynski (MK) and Bressan-William-Hill (BWH) models, combined with the Yld2000-2d yield function and the Swift hardening law. Uniaxial tension, disk compression and hydraulic bulge tests were performed to determine the yield loci and hardening curves of both materials. Meanwhile, the strain rate sensitivity (SRS) coefficient was measured through uniaxial tension tests carried out at different strain rates. Out-of-plane stretching tests were conducted in sheet specimens to obtain the surface limit strains under different linear strain paths. Micrographs of the specimens fractured in different stress states were obtained by optical and scanning electron microscopy. The overall results show that the BWH model can predict the FLC better than the MK model, and that the SRS does not have much effect on the limit strains for both materials. The predicted FLCs and micrograph analysis both indicate that failure occurs by surface localized necking in uniaxial and plane strain tension states, whereas it occurs by localized shearing in the through thickness direction in balanced biaxial tension state.

Modern X-ray examination methods in differential diagnostics of various forms of lung hydatid disease; Sovremennye luchevye metody issledovanij v differentsial'noj diagnostike razlichnykh form ehkhinokokkoza legkikh

Energy Technology Data Exchange (ETDEWEB)

Akilova, D N [1-Tashkent state med. inst., Tashkent (Uzbekistan)

2003-02-15

This work analyzes possibilities of complex radiation diagnostics using traditional Xray, computer and magnet resonance tomography and ultrasonography based on examination and treatment of 223 patients with lung hydatid disease. The diagnosis of 187 out 223 patients has been confirmed during operations. Original methods of ultrasound' examination (USI) of lungs have been developed. The role and place of needle aspirated biopsy controlled by computer tomography in differential diagnostics of complicated forms of lung hydatid disease with various forms of tumors, tubercular caverns etc. have been identified. Self-descriptiveness, sensitivity and general accuracy of these examination methods have been studied on patients with non-complicated and complicated forms of lung hydatid disease. Self descriptiveness of X-ray for non-complicated forms was 104%, USI - 85%, CT 100%, for complicated forms self-descriptiveness of X-ray was 92%, CT- 97%. Ultrasound examination of chest allowed visualizing and localizing of hydatid cysts when they were peripheral. The research enabled to develop algorithm of diagnosing non-complicated and complicated forms of lung hydatid disease. Needle aspirated biopsy was applied in complicated cases. In non-complicated cases transcutaneous manipulations have not been performed to avoid the process dissemination. (author)

Colorimetric microdetermination of captopril in pure form and in pharmaceutical formulations

Science.gov (United States)

Shama, Sayed Ahmed; El-Sayed Amin, Alla; Omara, Hany

2006-11-01

A simple, rapid, accurate, precise and sensitive colorimetric method for the determination of captopril (CAP) in bulk sample and in dosage forms is described. The method is based on oxidation of the drug by potassium permanganate in acidic medium and determination of the unreacted oxidant by measuring the decrease in absorbance for five different dyes; methylene blue (MB); acid blue 74 (AB), acid red 73 (AR), amaranth dye (AM) and acid orange 7 (AO) at a suitable λmax (660, 610, 510, 520, and 485 nm), respectively. Regression analysis of Beer's plots showed good correlation in the concentration ranges (0.4 12.5, 0.3 10, 0.5 11, 0.4 8.3 and 0.5 9.3 μg ml-1), respectively. The apparent molar absorbtivity, Sandell sensitivity, detection and quantitation limits were calculated. For more accurate results, Ringbom optimum concentration ranges were 0.5 12, 0.5 9.6, 0.6 10.5, 0.5 8.0 and 0.7 9.0 μg ml-1, respectively. The validity of the proposed method was tested by analyzing in pure and dosage forms containing CAP whether alone or in combination with hydrochlorothiazide. Statistical analysis of the results reflects that the proposed procedures are precise, accurate and easily applicable for the determination of CAP in pure form and in pharmaceutical preparations. Also, the stability constant was determined and the free energy change was calculated potentiometrically.

Radioecological sensitivity

International Nuclear Information System (INIS)

Howard, Brenda J.; Strand, Per; Assimakopoulos, Panayotis

2003-01-01

After the release of radionuclide into the environment it is important to be able to readily identify major routes of radiation exposure, the most highly exposed individuals or populations and the geographical areas of most concern. Radioecological sensitivity can be broadly defined as the extent to which an ecosystem contributes to an enhanced radiation exposure to Man and biota. Radioecological sensitivity analysis integrates current knowledge on pathways, spatially attributes the underlying processes determining transfer and thereby identifies the most radioecologically sensitive areas leading to high radiation exposure. This identifies where high exposure may occur and why. A framework for the estimation of radioecological sensitivity with respect to humans is proposed and the various indicators by which it can be considered have been identified. These are (1) aggregated transfer coefficients (Tag), (2) action (and critical) loads, (3) fluxes and (4) individual exposure of humans. The importance of spatial and temporal consideration of all these outputs is emphasized. Information on the extent of radionuclide transfer and exposure to humans at different spatial scales is needed to reflect the spatial differences which can occur. Single values for large areas, such as countries, can often mask large variation within the country. Similarly, the relative importance of different pathways can change with time and therefore assessments of radiological sensitivity are needed over different time periods after contamination. Radioecological sensitivity analysis can be used in radiation protection, nuclear safety and emergency preparedness when there is a need to identify areas that have the potential of being of particular concern from a risk perspective. Prior identification of radioecologically sensitive areas and exposed individuals improve the focus of emergency preparedness and planning, and contribute to environmental impact assessment for future facilities. The

Quantum protocol for cheat-sensitive weak coin flipping.

Science.gov (United States)

Spekkens, R W; Rudolph, Terry

2002-11-25

We present a quantum protocol for the task of weak coin flipping. We find that, for one choice of parameters in the protocol, the maximum probability of a dishonest party winning the coin flip if the other party is honest is 1/sqrt[2]. We also show that if parties restrict themselves to strategies wherein they cannot be caught cheating, their maximum probability of winning can be even smaller. As such, the protocol offers additional security in the form of cheat sensitivity.

Fabrication of Two Columns Dye-Sensitized Solar-Cell

International Nuclear Information System (INIS)

Phyu Sin Khaing Oo; Su Su Hlaing; Khin Lay Thwe; Nwe Ni Khin

2011-12-01

A two columns dye-sensitized solar cell has been fabricated using dye extract form teak leaves. This solar cell was assembled with two 20-30 ohms conductive glasses (one for TiO2 coated electrode and another for carbon coated electrode), TiO2 nano-powder P25, iodide electrolyte solution and soft graphite pencil for carbon coating. It was found that the open circuit voltage Voc was 0.688V and the short circuit Isc was 0.724mA

Method Matters: Systematic Effects of Testing Procedure on Visual Working Memory Sensitivity

Science.gov (United States)

Makovski, Tal; Watson, Leah M.; Koutstaal, Wilma; Jiang, Yuhong V.

2010-01-01

Visual working memory (WM) is traditionally considered a robust form of visual representation that survives changes in object motion, observer's position, and other visual transients. This article presents data that are inconsistent with the traditional view. We show that memory sensitivity is dramatically influenced by small variations in the…

Radiation sensitive indicator based on tetrabromophenol blue dyed poly(vinyl alcohol)

International Nuclear Information System (INIS)

Beshir, W.B.

2013-01-01

Radiation sensitive indicators based on dyed polyvinyl alcohol (PVA) containing acid- sensitive dye (tetrabromophenol blue, TBPB) and chloral hydrate (CCl 3 ·CH·(OH) 2 , 2,2,2-trichloroethane-1,1-diol) have been developed. These plastic film dosimeters undergo color change from blue (the alkaline form of TBPB) to yellow (the acidic form of TBPB), indicating acid formation. The concentration of radiation formed acids in the films containing different concentrations of chloral hydrate was calculated at different doses. These films can be used as dosimeters for food irradiation applications where the maximum of the useful dose ranges are between 1 and 8 kGy depending on chloral hydrate concentration in the film. The films have the advantage of negligible humidity effects on response in the intermediate range of relative humidity from 0 to 70% as good post irradiation stability when stored in the dark at room temperature. The overall combined uncertainty (at 2σ) associated with measurement of response (ΔA mm −1 ) at 623 nm for dose range 1–8 kGy is 4.53%. - Highlights: ► On irradiating TBPB/PVA films the color change from blue to green and yellow. ► The amount of acid formed depends on dose and concentration of chloral hydrate. ► The dose range 1–8 kGy the film can be used for food irradiation applications. ► The response of these films has negligible humidity effects from 0 to 70%. ► The combined uncertainty at 2σ using TBPB/PVA films was found to be 4.53%

Studies on radiation-sensitive nonsilver halide materials, (2)

International Nuclear Information System (INIS)

Komizu, Hideo; Honda, Koichi; Yabe, Akira; Kawasaki, Masami; Yamanaka, Takeshi.

1980-01-01

Dye-precursors made from furfural and some aniline derivatives become red-colored upon irradiation with ionization radiatios in PVC matrix, forming Stenhouse salts with the HCl evolved from the matrix. The coloration of the precursor from N-methylaniline, having the most excellent potential for dosimetry among the precursors, was studied for the irradiation of electron beam (60 kV) and X-ray (50 - 240 kVp). The following conclusions were obtained for the electron beam bombardment. (1) The response range is 10 -8 - 10 -6 C/cm 2 or 10 3 - 10 5 rad, where good linearity between coloration and charge density exists. (2) The highest sensitivity is obtained when the concentration of the precursor is >=5 wt% for the amount of PVC and the film thickness is >=32 μm. (3) Addition of 25 wt% of DOP enhances not only the sensitivity by ca. 20% but also the stability of the color from several days to several months. (4) The sensitivity is increased by ca. 15% when a conductive base is used for the film. (5) G value for the formation of the dye, i.e., that for the formation of HCl is 13.5 - 15.5. The followings were obtained for the irradiation of X-ray. (1) The response range is 10 3 - 10 5 R or rad. (2) The sensitivity for the absorbed dose is independent of the energy but is approximately proportional to the film thickness. (3) The sensitivity is higher than that for electrons by the factor of ca. 1.6, reflecting the higher G(HCl) value, 23 - 25. (author)

Sensitivity of Pulsar Timing Arrays

Science.gov (United States)

Siemens, Xavier

2015-08-01

For the better part of the last decade, the North American Nanohertz Observatory for Gravitational Waves (NANOGrav) has been using the Green Bank and Arecibo radio telescopes to monitor millisecond pulsars. NANOGrav, along with similar international collaborations, the European Pulsar Timing Array and the Parkes Pulsar Timing Array in Australia, form a consortium of consortia: the International Pulsar Timing Array (IPTA). The goal of the IPTA is to directly detect low-frequency gravitational waves which cause small changes to the times of arrival of radio pulses from millisecond pulsars. In this talk I will discuss the work of NANOGrav and the IPTA as well as our sensitivity to gravitational waves from astrophysical sources. I will show that a detection is possible by the end of the decade.

Toward Analytic Solution of Nonlinear Differential Difference Equations via Extended Sensitivity Approach

International Nuclear Information System (INIS)

Darmani, G.; Setayeshi, S.; Ramezanpour, H.

2012-01-01

In this paper an efficient computational method based on extending the sensitivity approach (SA) is proposed to find an analytic exact solution of nonlinear differential difference equations. In this manner we avoid solving the nonlinear problem directly. By extension of sensitivity approach for differential difference equations (DDEs), the nonlinear original problem is transformed into infinite linear differential difference equations, which should be solved in a recursive manner. Then the exact solution is determined in the form of infinite terms series and by intercepting series an approximate solution is obtained. Numerical examples are employed to show the effectiveness of the proposed approach. (general)

pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

Science.gov (United States)

Chen, Daquan; Sun, Kaoxiang; Mu, Hongjie; Tang, Mingtan; Liang, Rongcai; Wang, Aiping; Zhou, Shasha; Sun, Haijun; Zhao, Feng; Yao, Jianwen; Liu, Wanhui

2012-01-01

Background In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS) polymer was used for vaginal administration. Methods The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment. Results A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0). Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0. Conclusion This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery. PMID:22679372

Neutron sensitivity of prompt-response self-powered neutron detectors and the interval rule

International Nuclear Information System (INIS)

Molina Avila, J.; Carmolopes, M.

1989-01-01

This paper is devoted to the calculation of thermal s th and epithermal s epi sensitivities of cobalt prompt-response Self-Powered Neutron Detectors (SPNDs). The thermal sensitivity was obtained for a Maxwellian neutron field, and the effect of scattering on the self-shielding correction was taken into consideration in the second-collision approximation. The dependence of s th on the emitter radius R was studied in a wide region of R (0.025 to 0.2 cm). The differential and global epithermal sensitivities were calculated using a simple expression for the first-collision neutron absorption probability. Finally, a criterion to evaluate the accuracy of the parameters of the model was established in the form of some Interval Rule which is very sensitive to the radial dependence of the flux perturbation correction and other parameters of the model in both the thermal and epithermal regions

Sensitivity and uncertainty studies of the CRAC2 computer code

International Nuclear Information System (INIS)

Kocher, D.C.; Ward, R.C.; Killough, G.G.; Dunning, D.E. Jr.; Hicks, B.B.; Hosker, R.P. Jr.; Ku, J.Y.; Rao, K.S.

1985-05-01

This report presents a study of the sensitivity of early fatalities, early injuries, latent cancer fatalities, and economic costs for hypothetical nuclear reactor accidents as predicted by the CRAC2 computer code (CRAC = Calculation of Reactor Accident Consequences) to uncertainties in selected models and parameters used in the code. The sources of uncertainty that were investigated in the CRAC2 sensitivity studies include (1) the model for plume rise, (2) the model for wet deposition, (3) the procedure for meteorological bin-sampling involving the selection of weather sequences that contain rain, (4) the dose conversion factors for inhalation as they are affected by uncertainties in the physical and chemical form of the released radionuclides, (5) the weathering half-time for external ground-surface exposure, and (6) the transfer coefficients for estimating exposures via terrestrial foodchain pathways. The sensitivity studies were performed for selected radionuclide releases, hourly meteorological data, land-use data, a fixed non-uniform population distribution, a single evacuation model, and various release heights and sensible heat rates. Two important general conclusions from the sensitivity and uncertainty studies are as follows: (1) The large effects on predicted early fatalities and early injuries that were observed in some of the sensitivity studies apparently are due in part to the presence of thresholds in the dose-response models. Thus, the observed sensitivities depend in part on the magnitude of the radionuclide releases. (2) Some of the effects on predicted early fatalities and early injuries that were observed in the sensitivity studies were comparable to effects that were due only to the selection of different sets of weather sequences in bin-sampling runs. 47 figs., 50 tabs

Radioactivity measurements for determining bacterial increase and sensitivity to antibiotics. [/sup 14/C tracer

Energy Technology Data Exchange (ETDEWEB)

Jaszsagi-Nagy, E [Magyar Tudomanyos Akademia, Budapest; Lendvay, J [Orszagos Frederic Joliot-Curie Sugarbiologiai es Sugaregeszsegugyi Kutato Intezet, Budapest (Hungary)

1976-01-01

The authors elaborated a sensitive and objective measuring method for determining the bacteria increase in biological material and the sensitivity to antibiotics. When /sup 14/C glucose is added to the medium as the single source of sugar, the respiratory carbon dioxide formed by the bacteria reflects the rate of increase. The released /sup 14/C dioxide can be measured continuously without loss to the environment and the degree of bacterial infection and the antibiotic activity, respectively, can be determined.

Sensitivity analysis

Science.gov (United States)

... page: //medlineplus.gov/ency/article/003741.htm Sensitivity analysis To use the sharing features on this page, please enable JavaScript. Sensitivity analysis determines the effectiveness of antibiotics against microorganisms (germs) ...

Molecular-thermodynamic theory of micellization of pH-sensitive surfactants.

Science.gov (United States)

Goldsipe, Arthur; Blankschtein, Daniel

2006-04-11

A predictive, molecular-thermodynamic theory is developed to model the micellization of pH-sensitive surfactants. The theory combines a molecular-thermodynamic description of micellization in binary surfactant mixtures with the protonation equilibrium of the surfactant monomers. The thermodynamic component of the theory models the pH-mediated equilibrium between micelles, surfactant monomers, and counterions. These counterions may originate from the surfactant or from added salt, acid, or base. The molecular component of the theory models the various contributions to the free energy of micellization, which corresponds to the free-energy change associated with forming a mixed micelle from the protonated and deprotonated forms of the surfactant and from the bound counterions. The free energy of micellization includes hydrophobic, interfacial, packing, steric, electrostatic, and entropic contributions, which are all calculated molecularly. The theory also requires knowledge of the surfactant molecular structure and the solution conditions, including the temperature and the amount of any added salt, acid, or base. To account for the pH sensitivity of the surfactant, the theory requires knowledge of the surfactant monomer equilibrium deprotonation constant (pK1), which may be obtained from experimental titration data obtained below the critical micelle concentration (cmc). The theory can be utilized to predict the equilibrium micelle and solution properties, including the cmc, the micelle composition, the micelle shape and aggregation number, the solution pH, and the micelle deprotonation equilibrium constant (pKm). Theoretical predictions of the cmc, the micelle aggregation number, and the pKm compare favorably with the available experimental data for alkyldimethylamine oxide surfactants. This class of pH-sensitive surfactants exhibits a form of self-synergy, which has previously been attributed to hydrogen-bond formation at the micelle interface. Instead, we show that

Helium Compton Form Factor Measurements at CLAS

Energy Technology Data Exchange (ETDEWEB)

Voutier, Eric J.-M. [Laboratoire de Physique Subatomique et Cosmologie

2013-07-01

The distribution of the parton content of nuclei, as encoded via the generalized parton distributions (GPDs), can be accessed via the deeply virtual Compton scattering (DVCS) process contributing to the cross section for leptoproduction of real photons. Similarly to the scattering of light by a material, DVCS provides information about the dynamics and the spatial structure of hadrons. The sensitivity of this process to the lepton beam polarization allows to single-out the DVCS amplitude in terms of Compton form factors that contain GPDs information. The beam spin asymmetry of the $^4$He($\\vec {\\mathrm e}$,e$' \\gamma ^4$He) process was measured in the experimental Hall B of the Jefferson Laboratory to extract the real and imaginary parts of the twist-2 Compton form factor of the $^4$He nucleus. The experimental results reported here demonstrate the relevance of this method for such a goal, and suggest the dominance of the Bethe-Heitler amplitude to the unpolarized process in the kinematic range explored by the experiment.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

Energy Technology Data Exchange (ETDEWEB)

Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

2015-06-15

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

International Nuclear Information System (INIS)

Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

2015-01-01

Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

International Nuclear Information System (INIS)

Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

1987-01-01

The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size

Locally formed dopamine inhibits Na+-K+-ATPase activity in rat renal cortical tubule cells

International Nuclear Information System (INIS)

Seri, I.; Kone, B.C.; Gullans, S.R.; Aperia, A.; Brenner, B.M.; Ballermann, B.J.

1988-01-01

Dopamine, generated locally from L-dopa, inhibits Na + -K + -ATPase in permeabilized rat proximal tubules under maximum transport rate conditions for sodium. To determine whether locally formed dopamine inhibits Na + -K + -ATPase activity in intact cortical tubule cells we studied the effect of L-dopa on ouabain-sensitive oxygen consumption rate (Qo 2 ) and 86 Rb uptake in renal cortical tubule cell suspensions. L-Dopa did not affect ouabain-insensitive Qo 2 or mitochondrial respiration. However, L-dopa inhibited ouabain-sensitive Qo 2 in a concentration-dependent manner, with half-maximal inhibition (K 0.5 ) of 5 x 10 -7 M and a maximal inhibition of 14.1 ± 1.5% at 10 -4 M. L-Dopa also blunted the nystatin-stimulated Qo 2 in a concentration-dependent manner, indicating the L-dopa directly inhibits Na + -K + -ATPase activity and not sodium entry. Ouabain-sensitive 86 Rb uptake was also inhibited by L-dopa. Carbidopa, an inhibitor of the conversion of L-dopa to dopamine, eliminated the effect of L-dopa on ouabain-sensitive Qo 2 and 86 Rb uptake, indicating that dopamine rather than L-dopa was the active agent. The finding that the L-dopa concentration-response curve was shifted to the left by one order of magnitude in the presence of nystatin suggests that the inhibitory effect is enhanced when the intracellular sodium concentration is increased. By studying the effect of L-dopa on ouabain-sensitive Qo 2 at increasing extracellular sodium concentrations in the presence of nystatin, the authors demonstrated that the inhibitory effect of locally formed dopamine on the Na + -K + -ATPase is indeed dependent on the sodium available for the enzyme and occurs in an uncompetitive manner

Intratumoral Delivery of Doxorubicin on Folate-Conjugated Graphene Oxide by In-Situ Forming Thermo-Sensitive Hydrogel for Breast Cancer Therapy

Directory of Open Access Journals (Sweden)

Yi Teng Fong

2017-11-01

Full Text Available By taking advantage of the pH-sensitive drug release property of graphene oxide (GO after intracellular uptake, we prepared folic acid (FA-conjugated GO (GOFA for targeted delivery of the chemotherapeutic drug doxorubicin (DOX. GOFA-DOX was further encapsulated in an injectable in-situ forming thermo-sensitive hyaluronic acid-chitosan-g-poly(N-isopropylacrylamide (HACPN hydrogel for intratumoral delivery of DOX. As the degradation time of HACPN could be extended up to 3 weeks, intratumoral delivery of GOFA-DOX/HACPN could provide controlled and targeted delivery of DOX through slow degradation HACPN and subsequent cellular uptake of released GOFA-DOX by tumor cells through interactions of GOFA with folate receptors on the tumor cell’s surface. GOFA nano-carrier and HACPN hydrogel were first characterized for the physico-chemical properties. The drug loading experiments indicated the best preparation condition of GOFA-DOX was by reacting 0.1 mg GOFA with 2 mg DOX. GOFA-DOX showed pH-responsive drug release with ~5 times more DOX released at pH 5.5 than at pH 7.4 while only limited DOX was released from GOFA-DOX/HACPN at pH 7.4. Intracellular uptake of GOFA by endocytosis and release of DOX from GOFA-DOX in vitro could be confirmed from transmission electron microscopic and confocal laser scanning microscopic analysis with MCF-7 breast cancer cells. The targeting effect of FA was revealed when intracellular uptake of GOFA was blocked by excess FA. This resulted in enhanced in vitro cytotoxicity as revealed from the lower half maximal inhibitory concentration (IC50 value of GOFA-DOX (7.3 μg/mL compared with that of DOX (32.5 μg/mL and GO-DOX (10 μg/mL. The flow cytometry analysis indicated higher apoptosis rates for cells treated with GOFA-DOX (30% compared with DOX (8% and GO-DOX (11%. Animal studies were carried out with subcutaneously implanted MCF-7 cells in BALB/c nude mice and subject to intratumoral administration of drugs. The relative

Interactions between motion and form processing in the human visual system.

Science.gov (United States)

Mather, George; Pavan, Andrea; Bellacosa Marotti, Rosilari; Campana, Gianluca; Casco, Clara

2013-01-01

The predominant view of motion and form processing in the human visual system assumes that these two attributes are handled by separate and independent modules. Motion processing involves filtering by direction-selective sensors, followed by integration to solve the aperture problem. Form processing involves filtering by orientation-selective and size-selective receptive fields, followed by integration to encode object shape. It has long been known that motion signals can influence form processing in the well-known Gestalt principle of common fate; texture elements which share a common motion property are grouped into a single contour or texture region. However, recent research in psychophysics and neuroscience indicates that the influence of form signals on motion processing is more extensive than previously thought. First, the salience and apparent direction of moving lines depends on how the local orientation and direction of motion combine to match the receptive field properties of motion-selective neurons. Second, orientation signals generated by "motion-streaks" influence motion processing; motion sensitivity, apparent direction and adaptation are affected by simultaneously present orientation signals. Third, form signals generated by human body shape influence biological motion processing, as revealed by studies using point-light motion stimuli. Thus, form-motion integration seems to occur at several different levels of cortical processing, from V1 to STS.

Complement activation and liver impairment in trichloroethylene-sensitized BALB/c mice.

Science.gov (United States)

Zhang, Jiaxiang; Zha, Wansheng; Wang, Feng; Jiang, Tao; Xu, Shuhai; Yu, Junfeng; Zhou, Chengfan; Shen, Tong; Wu, Changhao; Zhu, Qixing

2013-01-01

Our recent studies have shown that trichloroethylene (TCE) was able to induce multisystem injuries in the form of occupational medicamentosa-like dermatitis, including skin, kidney, and liver damages. However, the role of complement activation in the immune-mediated liver injury is not known. This study examined the role of complement activation in the liver injury in a mouse model of TCE-induced sensitization. Treatment of female BALB/c mice with TCE under specific dosing protocols resulted in skin inflammation and sensitization. Skin edema and erythema occurred in TCE-sensitized groups. Trichloroethylene sensitization produced liver histopathological lesions, increased serum alanine aminotransferase, aspartate transaminase activities, and the relative liver weight. The concentrations of serum complement components C3a-desArg, C5a-desArg, and C5b-9 were significantly increased in 24-hour, 48-hour, and 72-hour sensitization-positive groups treated with TCE and peaked in the 72-hour sensitization-positive group. Depositions of C3a, C5a, and C5b-9 into the liver tissue were also revealed by immunohistochemistry. Immunofluorescence further verified high C5b-9 expression in 24-hour, 48-hour, and 72-hour sensitization-positive groups in response to TCE treatment. Reverse transcription-polymerase chain reaction detected C3 messenger RNA expression in the liver, and this was significantly increased in 24-hour and 48-hour sensitization-positive groups with a transient reduction at 72 hours. These results provide the first experimental evidence that complement activation may play a key role in the generation and progression of immune-mediated hepatic injury by exposure to TCE.

Noise sensitivity: symptoms, health status, illness behavior and co-occurring environmental sensitivities.

NARCIS (Netherlands)

Baliatsas, C.; Kamp, I. van; Swart, W.; Hooiveld, M.; Yzermans, J.

2016-01-01

Epidemiological evidence on the symptomatic profile, health status and illness behavior of people with subjective sensitivity to noise is still scarce. Also, it is unknown to what extent noise sensitivity co-occurs with other environmental sensitivities such as multi-chemical sensitivity and

Formulation and Analysis of an Approximate Expression for Voltage Sensitivity in Radial DC Distribution Systems

Directory of Open Access Journals (Sweden)

Ho-Yong Jeong

2015-08-01

Full Text Available Voltage is an important variable that reflects system conditions in DC distribution systems and affects many characteristics of a system. In a DC distribution system, there is a close relationship between the real power and the voltage magnitude, and this is one of major differences from the characteristics of AC distribution systems. One such relationship is expressed as the voltage sensitivity, and an understanding of voltage sensitivity is very useful to describe DC distribution systems. In this paper, a formulation for a novel approximate expression for the voltage sensitivity in a radial DC distribution system is presented. The approximate expression is derived from the power flow equation with some additional assumptions. The results of approximate expression is compared with an exact calculation, and relations between the voltage sensitivity and electrical quantities are analyzed analytically using both the exact form and the approximate voltage sensitivity equation.

Demystifying back scatter interferometry: a sensitive refractive index detector

DEFF Research Database (Denmark)

Jepsen, Søren Terpager; Jørgensen, Thomas Martini; Trydal, Torleif

2014-01-01

BACKGROUND: Back Scatter Interferometry (BSI) is a sensitive method for detecting changes of the refractive index (RI) in small capillaries. The method was originally developed as an off-axial column detector for use in Liquid Chromatography or Capillary Electrophoresis systems, but it has been...... acting like a common-path interferometer. METHODS: A HeNe laser is directed at a glass capillary with inner diameter of 1.4 mm and reflected light from air/glass and liquid/glass interfaces interfere to form an RI dependent intensity fringe pattern at a CCD detector. The fringe shift relative...... a common-path interferometer. The sensitivity of the BSI system is given by twice the inner diameter of the capillary times the wavenumber of the light source. Our results suggest that Back Scatter Interferometry does not provide a unique measurement principle for sensing biochemical bindings compared...

Responses to Varroa by honey bees with different levels of Varroa Sensitive Hygiene

Science.gov (United States)

The mite-resistance trait called suppression of mite reproduction (SMR) is a form of hygienic behavior that we have named varroa sensitive hygiene (VSH). With VSH, adult worker bees (Apis mellifera) disrupt the population growth of parasitic mites (Varroa destructor) by removing mite-infested bee p...

The forgotten form of knowledge

DEFF Research Database (Denmark)

Worsøe-Schmidt, Lisbeth

early Danish general periodicals show a different picture. During the first half of the 18th century, all sorts of stupid jokes, provocations and sharp attacks on dissenters thrived in a fashion rather similar to the kind of discourse frequently found on today's social media. But why and how did public...... discourse become more polished during the 18th century? Is it possible to generalize the process that discourse in early Danish journals underwent? And is there hope for today's public discourse on social media or are we lost in moral blindness and lack of sensitivity as Baumann puts it? The paper seeks......The forgotten form of knowledge: Similarities between early 18th century Danish journals and nowadays Facebook discourse. Contemplating the early display of the public sphere in the 18th century, one is struck by the ease with which participants conduct themselves within the emerging institution...

Nordic reference study on uncertainty and sensitivity analysis

International Nuclear Information System (INIS)

Hirschberg, S.; Jacobsson, P.; Pulkkinen, U.; Porn, K.

1989-01-01

This paper provides a review of the first phase of Nordic reference study on uncertainty and sensitivity analysis. The main objective of this study is to use experiences form previous Nordic Benchmark Exercises and reference studies concerning critical modeling issues such as common cause failures and human interactions, and to demonstrate the impact of associated uncertainties on the uncertainty of the investigated accident sequence. This has been done independently by three working groups which used different approaches to modeling and to uncertainty analysis. The estimated uncertainty interval for the analyzed accident sequence is large. Also the discrepancies between the groups are substantial but can be explained. Sensitivity analyses which have been carried out concern e.g. use of different CCF-quantification models, alternative handling of CCF-data, time windows for operator actions and time dependences in phase mission operation, impact of state-of-knowledge dependences and ranking of dominating uncertainty contributors. Specific findings with respect to these issues are summarized in the paper

Radioimmunoassay for free and bound forms of abscisic acid

International Nuclear Information System (INIS)

Cutting, J.G.; Hofman, P.J.; Wolstenholme, B.N.; Lishman, A.W.

1984-01-01

A radioimmunoassay (RIA) for the quanitation of abscisic acid (ABA) has been developed. The assay is extremely sensitive and measuring ranges extend from 10 pg to 10 ng. Although the assay was free of contaminant interference when applied to avocado material, crude extract analysis yielded a composite of free and bound forms of ABA. Equivalents of 20 mg of plant material were spotted onto silica gel plates (GF 245 solvent:toluene:ethyl acetate : acetic acid 25:15:3), developed and the relative Rf zones removed and subjected to RIA. The technique was tested on avocados

Calcium fluoride whispering gallery mode optical resonator with reduced thermal sensitivity

Science.gov (United States)

Savchenkov, Anatoliy; Matsko, Andrey

2018-03-01

We demonstrate a crystalline CaF2 resonator with thermal sensitivity of the optical modes approaching zero. The resonator is made by laminating a calcium fluoride layer forming an optical monolithic cavity with ceramic compensation layers. The ceramics is characterized with negative thermal expansion coefficient achievable in a certain temperature range. The thermally compensated resonator has a potential application for laser frequency stabilization.

Probabilistic sensitivity analysis of system availability using Gaussian processes

International Nuclear Information System (INIS)

Daneshkhah, Alireza; Bedford, Tim

2013-01-01

The availability of a system under a given failure/repair process is a function of time which can be determined through a set of integral equations and usually calculated numerically. We focus here on the issue of carrying out sensitivity analysis of availability to determine the influence of the input parameters. The main purpose is to study the sensitivity of the system availability with respect to the changes in the main parameters. In the simplest case that the failure repair process is (continuous time/discrete state) Markovian, explicit formulae are well known. Unfortunately, in more general cases availability is often a complicated function of the parameters without closed form solution. Thus, the computation of sensitivity measures would be time-consuming or even infeasible. In this paper, we show how Sobol and other related sensitivity measures can be cheaply computed to measure how changes in the model inputs (failure/repair times) influence the outputs (availability measure). We use a Bayesian framework, called the Bayesian analysis of computer code output (BACCO) which is based on using the Gaussian process as an emulator (i.e., an approximation) of complex models/functions. This approach allows effective sensitivity analysis to be achieved by using far smaller numbers of model runs than other methods. The emulator-based sensitivity measure is used to examine the influence of the failure and repair densities' parameters on the system availability. We discuss how to apply the methods practically in the reliability context, considering in particular the selection of parameters and prior distributions and how we can ensure these may be considered independent—one of the key assumptions of the Sobol approach. The method is illustrated on several examples, and we discuss the further implications of the technique for reliability and maintenance analysis

Characterization of Aluminum Magnesium Alloy Reverse Sensitized via Heat Treatment

Science.gov (United States)

2016-09-01

when magnesium comes out of solution as a second phase, Al3Mg2, on the grain boundaries, eventually forming a continuous network and increasing...alloys. Al-Mg alloys can become sensitized when magnesium comes out of solution as a second phase, Al3Mg2, on the grain boundaries, eventually...THIS PAGE INTENTIONALLY LEFT BLANK 1 I. INTRODUCTION A. MOTIVATION Aluminum alloys are attractive ship-building materials. They are lightweight

Catalysis by a de novo zinc-mediated protein interface: implications for natural enzyme evolution and rational enzyme engineering.

Science.gov (United States)

Der, Bryan S; Edwards, David R; Kuhlman, Brian

2012-05-08

Here we show that a recent computationally designed zinc-mediated protein interface is serendipitously capable of catalyzing carboxyester and phosphoester hydrolysis. Although the original motivation was to design a de novo zinc-mediated protein-protein interaction (called MID1-zinc), we observed in the homodimer crystal structure a small cleft and open zinc coordination site. We investigated if the cleft and zinc site at the designed interface were sufficient for formation of a primitive active site that can perform hydrolysis. MID1-zinc hydrolyzes 4-nitrophenyl acetate with a rate acceleration of 10(5) and a k(cat)/K(M) of 630 M(-1) s(-1) and 4-nitrophenyl phosphate with a rate acceleration of 10(4) and a k(cat)/K(M) of 14 M(-1) s(-1). These rate accelerations by an unoptimized active site highlight the catalytic power of zinc and suggest that the clefts formed by protein-protein interactions are well-suited for creating enzyme active sites. This discovery has implications for protein evolution and engineering: from an evolutionary perspective, three-coordinated zinc at a homodimer interface cleft represents a simple evolutionary path to nascent enzymatic activity; from a protein engineering perspective, future efforts in de novo design of enzyme active sites may benefit from exploring clefts at protein interfaces for active site placement.

Fast neutron sensitivity of polymer dosemeters

International Nuclear Information System (INIS)

Harper, M.W.; Pearson, D.W.; Moran, P.R.

1975-01-01

The responses of polymer thermocurrent dosemeters to fission spectrum and 14 MeV neutrons were measured. The dosemeters are in the form of disks 1 cm diam by 0.5 mm thick. Relative to Cobalt 60 gamma responses, teflon PTFE dosemeters show a 6 percent response to 14 MeV neutrons and a 5 percent response to fission neutrons on a tissue rad basis. Polymethylpentene dosemeters show a 49 percent response to 14 MeV neutrons and a 40 percent response to fission neutrons on a tissue rad basis when provided with adequate recoil proton buildup. The sensitivity of these dosemeters is limited to neutron doses greater than 10 rads by spurious background currents

Binding Affects the Tertiary and Quaternary Structures of the Shigella Translocator Protein IpaB and its Chaperone IpgC†

Science.gov (United States)

Adam, Philip R.; Patil, Mrinalini K.; Dickenson, Nicholas E.; Choudhari, Shyamal; Barta, Michael; Geisbrecht, Brian V.; Picking, Wendy L.; Picking, William D.

2012-01-01

Shigella flexneri uses its type III secretion system (T3SS) to promote invasion of human intestinal epithelial cells as the first step in causing shigellosis, a life threatening form of dysentery. The Shigella type III secretion apparatus (T3SA) consists of a basal body that spans the bacterial envelope and an exposed needle that injects effector proteins into target cells. The nascent Shigella T3SA needle is topped with a pentamer of the needle tip protein invasion plasmid antigen D (IpaD). Bile salts trigger recruitment of the first hydrophobic translocator protein, IpaB, to the tip complex where it senses contact with a host membrane. In the bacterial cytoplasm, IpaB exists in a complex with its chaperone IpgC. Several structures of IpgC have been solved and we recently reported the 2.1-Å crystal structure of the N-terminal domain (IpaB74.224) of IpaB. Like IpgC, the IpaB N-terminal domain exists as a homodimer in solution. We now report that when the two are mixed, these homodimers dissociate and form heterodimers having a nanomolar dissociation constant. This is consistent with the equivalent complexes co-purified after being co-expressed in E. coli. Fluorescence data presented here also indicate that the N-terminal domain of IpaB possesses two regions that appear to contribute additively to chaperone binding. It is also likely that the IpaB N terminus adopts an alternative conformation as a result of chaperone binding. The importance of these findings within the functional context of these proteins is discussed. PMID:22497344

Efficiency enhancement in dye-sensitized solar cells by in situ passivation of the sensitized nanoporous electrode with Li2CO3

International Nuclear Information System (INIS)

Zhang Jingbo; Zaban, Arie

2008-01-01

This work entails a method to improve the performance of dye-sensitized nanocrystalline TiO 2 solar cells by adding surface passivating elements to the electrolyte. The presence of either CO 2 , Li 2 CO 3 or K 2 CO 3 in electrolyte increases both the photocurrent and the photovoltage, resulting in higher overall conversion efficiency of these solar cells. The additives are used to form a passivation layer of lithium carbonate on the dye free surface of the TiO 2 nanoparticles and the conductive substrate. This layer suppresses the rate of the main recombination reaction between the photoinjected electrons and the oxidized ions in the electrolyte solution. While blocking part of the recombination, the lithium carbonate layer allows motion of the Li + ions towards the TiO 2 surface for charge screening. Consequently using this simple treatment, the conversion efficiency of dye-sensitized solar cell most improved by 17.2% (from 6.4% to 7.5%)

An Animal Model of Trichloroethylene-Induced Skin Sensitization in BALB/c Mice.

Science.gov (United States)

Wang, Hui; Zhang, Jia-xiang; Li, Shu-long; Wang, Feng; Zha, Wan-sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-xing

2015-01-01

Trichloroethylene (TCE) is a major occupational hazard and environmental contaminant that can cause multisystem disorders in the form of occupational medicamentosa-like dermatitis. Development of dermatitis involves several proinflammatory cytokines, but their role in TCE-mediated dermatitis has not been examined in a well-defined experimental model. In addition, few animal models of TCE sensitization are available, and the current guinea pig model has apparent limitations. This study aimed to establish a model of TCE-induced skin sensitization in BALB/c mice and to examine the role of several key inflammatory cytokines on TCE sensitization. The sensitization rate of dorsal painted group was 38.3%. Skin edema and erythema occurred in TCE-sensitized groups, as seen in 2,4-dinitrochlorobenzene (DNCB) positive control. Trichloroethylene sensitization-positive (dermatitis [+]) group exhibited increased thickness of epidermis, inflammatory cell infiltration, swelling, and necrosis in dermis and around hair follicle, but ear painted group did not show these histological changes. The concentrations of serum proinflammatory cytokines including tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and interleukin (IL)-2 were significantly increased in 24, 48, and 72 hours dermatitis [+] groups treated with TCE and peaked at 72 hours. Deposition of TNF-α, IFN-γ, and IL-2 into the skin tissue was also revealed by immunohistochemistry. We have established a new animal model of skin sensitization induced by repeated TCE stimulations, and we provide the first evidence that key proinflammatory cytokines including TNF-α, IFN-γ, and IL-2 play an important role in the process of TCE sensitization. © The Author(s) 2015.

Thyroid antibody-negative euthyroid Graves’ ophthalmopathy

Directory of Open Access Journals (Sweden)

Arshiya Tabasum

2016-06-01

Full Text Available TSH receptor antibodies (TRAbs are the pathological hallmark of Graves’ disease, present in nearly all patients with the disease. Euthyroid Graves’ ophthalmopathy (EGO is a well-recognized clinical entity, but its occurrence in patients with negative TRAbs is a potential source of diagnostic confusion. A 66-year-old female presented to our endocrinology clinic with right eye pain and diplopia in the absence of thyroid dysfunction. TRAbs were negative, as measured with a highly sensitive third-generation thyrotropin-binding inhibitory immunoglobulin (TBII ELISA assay. CT and MRI scans of the orbit showed asymmetrical thickening of the inferior rectus muscles but no other inflammatory or malignant orbital pathology. Graves’ ophthalmopathy (GO was diagnosed on the basis of the clinical and radiological features, and she underwent surgical recession of the inferior rectus muscle with complete resolution of the diplopia and orbital pain. She remained euthyroid over the course of follow-up but ultimately developed overt clinical and biochemical hyperthyroidism, 24 months after the initial presentation. By this time, she had developed positive TRAb as well as thyroid peroxidase antibodies. She responded to treatment with thionamides and remains euthyroid. This case highlights the potential for negative thyroid-specific autoantibodies in the presentation of EGO and underscores the variable temporal relationship between the clinical expression of thyroid dysfunction and orbital disease in the natural evolution of Graves’ disease.

Sensitivity theory for general non-linear algebraic equations with constraints

International Nuclear Information System (INIS)

Oblow, E.M.

1977-04-01

Sensitivity theory has been developed to a high state of sophistication for applications involving solutions of the linear Boltzmann equation or approximations to it. The success of this theory in the field of radiation transport has prompted study of possible extensions of the method to more general systems of non-linear equations. Initial work in the U.S. and in Europe on the reactor fuel cycle shows that the sensitivity methodology works equally well for those non-linear problems studied to date. The general non-linear theory for algebraic equations is summarized and applied to a class of problems whose solutions are characterized by constrained extrema. Such equations form the basis of much work on energy systems modelling and the econometrics of power production and distribution. It is valuable to have a sensitivity theory available for these problem areas since it is difficult to repeatedly solve complex non-linear equations to find out the effects of alternative input assumptions or the uncertainties associated with predictions of system behavior. The sensitivity theory for a linear system of algebraic equations with constraints which can be solved using linear programming techniques is discussed. The role of the constraints in simplifying the problem so that sensitivity methodology can be applied is highlighted. The general non-linear method is summarized and applied to a non-linear programming problem in particular. Conclusions are drawn in about the applicability of the method for practical problems

Learning course adjustments during arm movements with reversed sensitivity derivatives

Directory of Open Access Journals (Sweden)

Tweed Douglas B

2010-11-01

Full Text Available Abstract Background To learn, a motor system needs to know its sensitivity derivatives, which quantify how its neural commands affect motor error. But are these derivatives themselves learned, or are they known solely innately? Here we test a recent theory that the brain's estimates of sensitivity derivatives are revisable based on sensory feedback. In its simplest form, the theory says that each control system has a single, adjustable estimate of its sensitivity derivatives which affects all aspects of its task, e.g. if you learn to reach to mirror-reversed targets then your revised estimate should reverse not only your initial aiming but also your online course adjustments when the target jumps in mid-movement. Methods Human subjects bent a joystick to move a cursor to a target on a computer screen, but the cursor's motion was reversed relative to the joystick's. The target jumped once during each movement. Subjects had up to 4000 trials to practice aiming and responding to target jumps. Results All subjects learned to reverse both initial aiming and course adjustments. Conclusions Our study confirms that sensitivity derivatives can be relearned. It is consistent with the idea of a single, all-purpose estimate of those derivatives; and it suggests that the estimate is a function of context, as one would expect given that the true sensitivity derivatives may vary with the state of the controlled system, the target, and the motor commands.

Measurement of neutron sensitivity of self powered neutron detectors

International Nuclear Information System (INIS)

Mahant, A.K.; Yeshuraja, V.; Ghodke, Shobha

2005-01-01

Self powered neutron detectors (SPNDs ) will form the part of Reactor Instrumentation in the upcoming 500 MWe power reactors. ECIL has developed Vanadium and Cobalt SPNDs for NPCIL to be used in regulation and protection channels. Experimental determination of neutron sensitivity of the vanadium and cobalt Self Powered Neutron Detectors (SPNDs) was carried out in A-l location of Apsara reactor at BARC. The measurements involved determination of total detector signal, its various components and the thermal neutron flux at the detector location. The paper describes the experimental techniques used to measure various parameters required to evaluate the neutron sensitivity of the SPNDs and also the parameters required to ascertain the integrity of SPNDs. Neutron flux measurement was done by gold foil irradiation technique. The predominant signal component from the vanadium SPND is Ib the current due to activation of the vanadium emitter, it forms about 85% of the total signal. The other components I n,γ due to the capture gamma rays of 52 V and I externalγ produced by the external reactor gamma rays contribute about 10% and 5% respectively to the total signal. Whereas in the cobalt SPND the main signal component is due to the capture gamma rays of 60 Co and accounts for about the 95% of the total signal. Remaining 5% signal is due to external reactor gamma rays. (author)

Light-sensitive elements for radiographic use and process for the formation of an X-ray image

International Nuclear Information System (INIS)

Bussi, G.; Cavallo, E.

1990-01-01

A light-sensitive silver halide element for radiographic use with X-ray intensifying screens comprising coated on at least one side of a transparent support base at least a spectrally sensitized silver halide emulsion layer and, between the base and a silver halide emulsion layer, a hydrophillic colloid layer containing a) substantially light-insensitivelow iodide silver bromoiodide grains having an avergae grain size in therange of from 0.01 to 0.1 μm on which a spectral sensitizing dye is adsorbed to form a J-band, said dye adsorbed on said grains having a significant portion of its absorption in a region of the electromagnetic spectrum corresponding substantially to the spectral sensitivity of the silver halide emulsion, and b) dispersed zinc oxide particles. The invention allows the use of low coverage weights of silver halide light-sensitive elements and provides X-ray images with a favorable image quality and sensitivity ratio. (author)

Light-sensitive elements for radiographic use and process for the formation of an X-ray image

Energy Technology Data Exchange (ETDEWEB)

Bussi, G; Cavallo, E

1990-12-15

A light-sensitive silver halide element for radiographic use with X-ray intensifying screens comprising coated on at least one side of a transparent support base at least a spectrally sensitized silver halide emulsion layer and, between the base and a silver halide emulsion layer, a hydrophillic colloid layer containing (a) substantially light-insensitivelow iodide silver bromoiodide grains having an avergae grain size in therange of from 0.01 to 0.1 {mu}m on which a spectral sensitizing dye is adsorbed to form a J-band, said dye adsorbed on said grains having a significant portion of its absorption in a region of the electromagnetic spectrum corresponding substantially to the spectral sensitivity of the silver halide emulsion, and (b) dispersed zinc oxide particles. The invention allows the use of low coverage weights of silver halide light-sensitive elements and provides X-ray images with a favorable image quality and sensitivity ratio. (author).

Parity Violation in Elastic Electron-Proton Scattering and the Proton's Strange Magnetic Form Factor

International Nuclear Information System (INIS)

Spayde, D. T.; Averett, T.; Barkhuff, D.; Beck, D. H.; Beise, E. J.; Benson, C.; Breuer, H.; Carr, R.; Covrig, S.; DelCorso, J.

2000-01-01

We report a new measurement of the parity-violating asymmetry in elastic electron scattering from the proton at backward scattering angles. This asymmetry is sensitive to the strange magnetic form factor of the proton as well as electroweak axial radiative corrections. The new measurement of A=-4.92±0.61±0.73 ppm provides a significant constraint on these quantities. The implications for the strange magnetic form factor are discussed in the context of theoretical estimates for the axial corrections. (c) 2000 The American Physical Society

Noise sensitivity: Symptoms, health status, illness behavior and co-occurring environmental sensitivities

Energy Technology Data Exchange (ETDEWEB)

Baliatsas, Christos, E-mail: c.baliatsas@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands); Kamp, Irene van, E-mail: irene.van.kamp@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Swart, Wim, E-mail: wim.swart@rivm.nl [National Institute for Public Health and the Environment (RIVM), Bilthoven (Netherlands); Hooiveld, Mariëtte, E-mail: m.hooiveld@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands); Yzermans, Joris, E-mail: J.Yzermans@nivel.nl [Netherlands Institute for Health Services Research (NIVEL), Utrecht (Netherlands)

2016-10-15

Epidemiological evidence on the symptomatic profile, health status and illness behavior of people with subjective sensitivity to noise is still scarce. Also, it is unknown to what extent noise sensitivity co-occurs with other environmental sensitivities such as multi-chemical sensitivity and sensitivity to electromagnetic fields (EMF). A cross-sectional study performed in the Netherlands, combining self-administered questionnaires and electronic medical records of non-specific symptoms (NSS) registered by general practitioners (GP) allowed us to explore this further. The study sample consisted of 5806 participants, drawn from 21 general practices. Among participants, 722 (12.5%) responded “absolutely agree” to the statement “I am sensitive to noise”, comprising the high noise-sensitive (HNS) group. Compared to the rest of the sample, people in the HNS group reported significantly higher scores on number and duration of self-reported NSS, increased psychological distress, decreased sleep quality and general health, more negative symptom perceptions and higher prevalence of healthcare contacts, GP-registered NSS and prescriptions for antidepressants and benzodiazepines. These results remained robust after adjustment for demographic, residential and lifestyle characteristics, objectively measured nocturnal noise exposure from road-traffic and GP-registered morbidity. Co-occurrence rates with other environmental sensitivities varied between 9% and 50%. Individuals with self-declared sensitivity to noise are characterized by high prevalence of multiple NSS, poorer health status and increased illness behavior independently of noise exposure levels. Findings support the notion that different types of environmental sensitivities partly overlap. - Highlights: • People with self-reported noise sensitivity experience multiple non-specific symptoms. • They also report comparatively poorer health and increased illness behavior. • Co-occurrence with other

Noise sensitivity: Symptoms, health status, illness behavior and co-occurring environmental sensitivities

International Nuclear Information System (INIS)

Baliatsas, Christos; Kamp, Irene van; Swart, Wim; Hooiveld, Mariëtte; Yzermans, Joris

2016-01-01

Epidemiological evidence on the symptomatic profile, health status and illness behavior of people with subjective sensitivity to noise is still scarce. Also, it is unknown to what extent noise sensitivity co-occurs with other environmental sensitivities such as multi-chemical sensitivity and sensitivity to electromagnetic fields (EMF). A cross-sectional study performed in the Netherlands, combining self-administered questionnaires and electronic medical records of non-specific symptoms (NSS) registered by general practitioners (GP) allowed us to explore this further. The study sample consisted of 5806 participants, drawn from 21 general practices. Among participants, 722 (12.5%) responded “absolutely agree” to the statement “I am sensitive to noise”, comprising the high noise-sensitive (HNS) group. Compared to the rest of the sample, people in the HNS group reported significantly higher scores on number and duration of self-reported NSS, increased psychological distress, decreased sleep quality and general health, more negative symptom perceptions and higher prevalence of healthcare contacts, GP-registered NSS and prescriptions for antidepressants and benzodiazepines. These results remained robust after adjustment for demographic, residential and lifestyle characteristics, objectively measured nocturnal noise exposure from road-traffic and GP-registered morbidity. Co-occurrence rates with other environmental sensitivities varied between 9% and 50%. Individuals with self-declared sensitivity to noise are characterized by high prevalence of multiple NSS, poorer health status and increased illness behavior independently of noise exposure levels. Findings support the notion that different types of environmental sensitivities partly overlap. - Highlights: • People with self-reported noise sensitivity experience multiple non-specific symptoms. • They also report comparatively poorer health and increased illness behavior. • Co-occurrence with other

Reporter-nanobody fusions (RANbodies) as versatile, small, sensitive immunohistochemical reagents.

Science.gov (United States)

Yamagata, Masahito; Sanes, Joshua R

2018-02-27

Sensitive and specific antibodies are essential for detecting molecules in cells and tissues. However, currently used polyclonal and monoclonal antibodies are often less specific than desired, difficult to produce, and available in limited quantities. A promising recent approach to circumvent these limitations is to employ chemically defined antigen-combining domains called "nanobodies," derived from single-chain camelid antibodies. Here, we used nanobodies to prepare sensitive unimolecular detection reagents by genetically fusing cDNAs encoding nanobodies to enzymatic or antigenic reporters. We call these fusions between a reporter and a nanobody "RANbodies." They can be used to localize epitopes and to amplify signals from fluorescent proteins. They can be generated and purified simply and in unlimited amounts and can be preserved safely and inexpensively in the form of DNA or digital sequence.

Allergic sensitization

DEFF Research Database (Denmark)

van Ree, Ronald; Hummelshøj, Lone; Plantinga, Maud

2014-01-01

Allergic sensitization is the outcome of a complex interplay between the allergen and the host in a given environmental context. The first barrier encountered by an allergen on its way to sensitization is the mucosal epithelial layer. Allergic inflammatory diseases are accompanied by increased pe...

DDASAC, Double-Precision Differential or Algebraic Sensitivity Analysis

International Nuclear Information System (INIS)

Caracotsios, M.; Stewart, W.E.; Petzold, L.

1997-01-01

1 - Description of program or function: DDASAC solves nonlinear initial-value problems involving stiff implicit systems of ordinary differential and algebraic equations. Purely algebraic nonlinear systems can also be solved, given an initial guess within the region of attraction of a solution. Options include automatic reconciliation of inconsistent initial states and derivatives, automatic initial step selection, direct concurrent parametric sensitivity analysis, and stopping at a prescribed value of any user-defined functional of the current solution vector. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the sensitivities on request. 2 - Method of solution: Reconciliation of initial conditions is done with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithm of Shampine (1987), extended here to differential-algebraic equation systems. The solution is continued with the DASSL predictor- corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase detected and with row scaling of the Jacobian added. The backward-difference formulas for the predictor and corrector are expressed in divide-difference form, and the fixed-leading-coefficient form of the corrector (Jackson and Sacks-Davis 1980, Brenan et al. 1989) is used. Weights for error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations as given by Catacotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigns the work array lengths and the output unit. The machine number range and precision are determined at run time by a

PDASAC, Partial Differential Sensitivity Analysis of Stiff System

International Nuclear Information System (INIS)

Caracotsios, M.; Stewart, W.E.

2001-01-01

1 - Description of program or function: PDASAC solves stiff, nonlinear initial-boundary-value problems in a timelike dimension t and a space dimension x. Plane, circular cylindrical or spherical boundaries can be handled. Mixed-order systems of partial differential and algebraic equations can be analyzed with members of order or 0 or 1 in t, 0, 1 or 2 in x. Parametric sensitivities of the calculated states are computed simultaneously on request, via the Jacobian of the state equations. Initial and boundary conditions are efficiently reconciled. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the parametric sensitivities if desired. 2 - Method of solution: The method of lines is used, with a user- selected x-grid and a minimum-bandwidth finite-difference approximations of the x-derivatives. Starting conditions are reconciled with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithms of Shampine (1987), extended here to differential- algebraic equation systems. The solution is continued with the DASSL predictor-corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase deleted and with row scaling of the Jacobian added. The predictor and corrector are expressed in divided-difference form, with the fixed-leading-coefficient form of corrector (Jackson and Sacks-Davis 1989; Brenan et al. 1989). Weights for the error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations of Caracotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic equation systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigned the work array lengths and the output

Identification of seismically risk-sensitive systems and components in nuclear power plants: feasibility study

International Nuclear Information System (INIS)

Azarm, M.; Boccio, J.; Farahzad, P.

1983-06-01

An approach for the identification of risk-sensitive components in a nuclear power plant during and after a seismic event is described. Application of the methodology to two hypothetical power plants - a Boiling Water Reactor and a Pressurized Water Reactor - are presented and the results are given in tabular and graphical form. Conclusions drawn and lessons learned through the course of this study, based on the relative importance of various accident scenarios and sensitivity analyses, are discussed. In addition, the areas that may need further investigation are identified

Auxotrophy-stimulated sensitivity to quaternary ammonium salts and its relation to active transport in yeast

International Nuclear Information System (INIS)

Lachowicz, T.M.; Oblak, E.; Piatkowski, J.

1992-01-01

In previous studies we have observed that auxotrophic mutants of yeast were much more sensitive to quaternary ammonium salts than the corresponding isogenic wild type strains. The super sensitivity of the auxotrophs seems to be a characteristic feature of yeast and yeast-like microorganisms: the level of sensitivity of the quaternary ammonium salts of the bacterial auxotrophs and their original prototrophic forms appeared to be the same. The super sensitivity of yeast auxotrophs disappeared on minimal media with ammonium as a nitrogen source. In this report there are presented the data indicating that enrichment of the minimal medium with arginine restores the super sensitivity of auxotrophic yeast mutants to the quaternary ammonium salts. The results of amino-acid transport into the auxotrophic yeast cells treated with a quaternary ammonium salt in the presence and absence of arginine are given. A working hypothesis of the mechanism of these salts action as a specific inhibition of nutrient transport is discussed. (author). 19 refs, 3 figs, 8 figs

Note: Anodic bonding with cooling of heat-sensitive areas

DEFF Research Database (Denmark)

Vesborg, Peter Christian Kjærgaard; Olsen, Jakob Lind; Henriksen, Toke Riishøj

2010-01-01

Anodic bonding of silicon to glass always involves heating the glass and device to high temperatures so that cations become mobile in the electric field. We present a simple way of bonding thin silicon samples to borosilicate glass by means of heating from the glass side while locally cooling hea......-sensitive areas from the silicon side. Despite the high thermal conductivity of silicon, this method allows a strong anodic bond to form just millimeters away from areas essentially at room temperature....

Crystal Structure and Functional Characterization of the Complement Regulator Mannose-binding Lectin (MBL)/Ficolin-associated Protein-1 (MAP-1)

DEFF Research Database (Denmark)

Skjoedt, M.-o.; Roversi, P.; Hummelshoj, T.

2012-01-01

.5 nM, respectively. We studied structural aspects of MAP-1 and could show by multi-angle laser light scattering that MAP-1 forms a calcium-dependent homo-dimer in solution. We were able to determine the crystal structure of MAP-1, which also contains a head-to-tail dimer approximately 146 Angstrom...... long. This structure of MAP-1 also enables modeling and assembly of the MASP-1 molecule in its entirety. Finally we found that MAP-1 competes with all three MASPs for ligand binding and is able to mediate a strong dose dependent inhibitory effect on the lectin pathway activation, as measured by levels...

Crystal structure of the Rasputin NTF2-like domain from Drosophila melanogaster.

Science.gov (United States)

Vognsen, Tina; Kristensen, Ole

2012-03-30

The crystal structure of the NTF2-like domain of the Drosophila homolog of Ras GTPase SH3 Binding Protein (G3BP), Rasputin, was determined at 2.7Å resolution. The overall structure is highly similar to nuclear transport factor 2: It is a homodimer comprised of a β-sheet and three α-helices forming a cone-like shape. However, known binding sites for RanGDP and FxFG containing peptides show electrostatic and steric differences compared to nuclear transport factor 2. A HEPES molecule bound in the structure suggests a new, and possibly physiologically relevant, ligand binding site. Copyright © 2012 Elsevier Inc. All rights reserved.

Light Responsive Two-Component Supramolecular Hydrogel: A Sensitive Platform for Humidity Sensors

KAUST Repository

Samai, Suman

2016-02-15

The supramolecular assembly of anionic azobenzene dicarboxylate and cationic cetyltrimethylammonium bromide (CTAB) formed a stimuli responsive hydrogel with a critical gelation concentration (CGC) of 0.33 wt%. This self-sustainable two-component system was able to repair damage upon light irradiation. Moreover, it was successfully employed in the fabrication of highly sensitive humidity sensors for the first time.

Light Responsive Two-Component Supramolecular Hydrogel: A Sensitive Platform for Humidity Sensors

KAUST Repository

Samai, Suman; Sapsanis, Christos; Patil, Sachin; Ezzeddine, Alaa; Moosa, Basem; Omran, Hesham; Emwas, Abdul-Hamid M.; Salama, Khaled N.; Khashab, Niveen M.

2016-01-01

The supramolecular assembly of anionic azobenzene dicarboxylate and cationic cetyltrimethylammonium bromide (CTAB) formed a stimuli responsive hydrogel with a critical gelation concentration (CGC) of 0.33 wt%. This self-sustainable two-component system was able to repair damage upon light irradiation. Moreover, it was successfully employed in the fabrication of highly sensitive humidity sensors for the first time.

Influence of the embedded structure on the efp formation of compact terminal sensitive projectile

NARCIS (Netherlands)

Boyang, Xing; Rongzhong, Liu; Rui, Guo; Liang, Chen; Hao, Zhou; Yongliang, Yang; Lei, Liu

2017-01-01

To improve the damage efficiency of compact terminal sensitive projectile with EFP warhead, it is vital to understand how the embedded structure (ES) affects the EFP forming performance. In this paper, the corresponding numerical investigation is focused on, in which the fluid-structure interaction

Influence of the embedded structure on the EFP formation of compact terminal sensitive projectile

NARCIS (Netherlands)

Xing, Bo yang; Liu, Rong zhong; Guo, Rui; Chen, Liang; Zhou, Hao; Yang, Yong liang; Liu, Lei

2017-01-01

To improve the damage efficiency of compact terminal sensitive projectile with EFP warhead, it is vital to understand how the embedded structure (ES) affects the EFP forming performance. In this paper, the corresponding numerical investigation is focused on, in which the fluid-structure interaction

Influences of the embedded structure on the efp formation of compact terminal sensitive projectile

NARCIS (Netherlands)

Boyang, Xing; Rongzhong, Liu; Rui, Guo; Liang, Chen; Hao, Zhou; Yongliang, Yang; Lei, Liu

2017-01-01

To improve the damage efficiency of the compact terminal sensitive projectile with EFP warhead, it is vital to understand how the embedded structure (ES) affects the EFP forming performance. In this paper, the corresponding numerical investigation is focused on, where the fluid-structure interaction

Poisson and negative binomial item count techniques for surveys with sensitive question.

Science.gov (United States)

Tian, Guo-Liang; Tang, Man-Lai; Wu, Qin; Liu, Yin

2017-04-01

Although the item count technique is useful in surveys with sensitive questions, privacy of those respondents who possess the sensitive characteristic of interest may not be well protected due to a defect in its original design. In this article, we propose two new survey designs (namely the Poisson item count technique and negative binomial item count technique) which replace several independent Bernoulli random variables required by the original item count technique with a single Poisson or negative binomial random variable, respectively. The proposed models not only provide closed form variance estimate and confidence interval within [0, 1] for the sensitive proportion, but also simplify the survey design of the original item count technique. Most importantly, the new designs do not leak respondents' privacy. Empirical results show that the proposed techniques perform satisfactorily in the sense that it yields accurate parameter estimate and confidence interval.

Sevoflurane anaesthesia for nasal surgery in a patient with multiple chemical sensitivity.

Science.gov (United States)

Fernández Martín, M T; Álvarez López, J C

2018-01-01

Multiple chemical sensitivity syndrome is a group of complex disorders that include psychiatric disorders, chronic fatigue and/or respiratory problems. This syndrome could be triggered by specific allergens and toxins that cause neurophysiological sensitization and the appearance of the clinical symptomatology. Anaesthesia for these patients always poses a challenge for the anaesthetist, because they need to find and use drugs that do not trigger or aggravate the symptoms of the disease. Therefore, sevoflurane in these circumstances might be "the ideal anaesthetic". Performing general anaesthesia with sevoflurane as the sole anaesthetic agent, together with a series of environmental measures formed the basis for successful anaesthesia and surgery in our patient with a multiple chemical sensitivity syndrome. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

Study of stability of chloramphenicol in different forms to gamma radiation

International Nuclear Information System (INIS)

Tawfik, Z.S.

1985-01-01

The effect of radiation dose, in the range from 5 KGY to 250 KGY, on chloramphenicol in either the solid form or as aqueous solution was studied. The results obtained showed that the radiation had no effect on the antibiotic when it was irradiated in the solid form. Minor changes were detected when the antibiotic was exposed to radiation in solution, at doses as small as 5 KGY. These changes were detected by UV-visible, infrared and HPLC techniques. Bioassay experiments performed using the antibiotic concentration recommended by pharmacopoeia were not sensitive enough to detect these small changes. Lower concentrations of the studied antibiotic in the chloramphenicol as a result of exposure to radiation in solution or as eye drops. Accordingly, sterilization of chloramphenicol using gamma radiation could be considered a safe process if the antibiotic is in the solid form but aqueous solutions of the studied antibiotic are not recommended for sterilization by gamma radiation. (author)

Improved failure prediction in forming simulations through pre-strain mapping

Science.gov (United States)

Upadhya, Siddharth; Staupendahl, Daniel; Heuse, Martin; Tekkaya, A. Erman

2018-05-01

The sensitivity of sheared edges of advanced high strength steel (AHSS) sheets to cracking during subsequent forming operations and the difficulty to predict this failure with any degree of accuracy using conventionally used FLC based failure criteria is a major problem plaguing the manufacturing industry. A possible method that allows for an accurate prediction of edge cracks is the simulation of the shearing operation and carryover of this model into a subsequent forming simulation. But even with an efficient combination of a solid element shearing operation and a shell element forming simulation, the need for a fine mesh, and the resulting high computation time makes this approach not viable from an industry point of view. The crack sensitivity of sheared edges is due to work hardening in the shear-affected zone (SAZ). A method to predict plastic strains induced by the shearing process is to measure the hardness after shearing and calculate the ultimate tensile strength as well as the flow stress. In combination with the flow curve, the relevant strain data can be obtained. To eliminate the time-intensive shearing simulation necessary to obtain the strain data in the SAZ, a new pre-strain mapping approach is proposed. The pre-strains to be mapped are, hereby, determined from hardness values obtained in the proximity of the sheared edge. To investigate the performance of this approach the ISO/TS 16630 hole expansion test was simulated with shell elements for different materials, whereby the pre-strains were mapped onto the edge of the hole. The hole expansion ratios obtained from such pre-strain mapped simulations are in close agreement with the experimental results. Furthermore, the simulations can be carried out with no increase in computation time, making this an interesting and viable solution for predicting edge failure due to shearing.

Correlation of Diffusion and Metabolic Alterations in Different Clinical Forms of Multiple Sclerosis

Science.gov (United States)

Hannoun, Salem; Bagory, Matthieu; Durand-Dubief, Francoise; Ibarrola, Danielle; Comte, Jean-Christophe; Confavreux, Christian; Cotton, Francois; Sappey-Marinier, Dominique

2012-01-01

Diffusion tensor imaging (DTI) and MR spectroscopic imaging (MRSI) provide greater sensitivity than conventional MRI to detect diffuse alterations in normal appearing white matter (NAWM) of Multiple Sclerosis (MS) patients with different clinical forms. Therefore, the goal of this study is to combine DTI and MRSI measurements to analyze the relation between diffusion and metabolic markers, T2-weighted lesion load (T2-LL) and the patients clinical status. The sensitivity and specificity of both methods were then compared in terms of MS clinical forms differentiation. MR examination was performed on 71 MS patients (27 relapsing remitting (RR), 26 secondary progressive (SP) and 18 primary progressive (PP)) and 24 control subjects. DTI and MRSI measurements were obtained from two identical regions of interest selected in left and right centrum semioval (CSO) WM. DTI metrics and metabolic contents were significantly altered in MS patients with the exception of N-acetyl-aspartate (NAA) and NAA/Choline (Cho) ratio in RR patients. Significant correlations were observed between diffusion and metabolic measures to various degrees in every MS patients group. Most DTI metrics were significantly correlated with the T2-LL while only NAA/Cr ratio was correlated in RR patients. A comparison analysis of MR methods efficiency demonstrated a better sensitivity/specificity of DTI over MRSI. Nevertheless, NAA/Cr ratio could distinguish all MS and SP patients groups from controls, while NAA/Cho ratio differentiated PP patients from controls. This study demonstrated that diffusivity changes related to microstructural alterations were correlated with metabolic changes and provided a better sensitivity to detect early changes, particularly in RR patients who are more subject to inflammatory processes. In contrast, the better specificity of metabolic ratios to detect axonal damage and demyelination may provide a better index for identification of PP patients. PMID:22479330

Central sensitization: implications for the diagnosis and treatment of pain.

Science.gov (United States)

Woolf, Clifford J

2011-03-01

first discovery of activity-dependent synaptic plasticity in the spinal cord and the revelation that it occurs and produces pain hypersensitivity in patients. Nevertheless, discovering the genetic and environmental contributors to and objective biomarkers of central sensitization will be highly beneficial, as will additional treatment options to prevent or reduce this prevalent and promiscuous form of pain plasticity. Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Stereo chromatic contrast sensitivity model to blue-yellow gratings.

Science.gov (United States)

Yang, Jiachen; Lin, Yancong; Liu, Yun

2016-03-07

As a fundamental metric of human visual system (HVS), contrast sensitivity function (CSF) is typically measured by sinusoidal gratings at the detection of thresholds for psychophysically defined cardinal channels: luminance, red-green, and blue-yellow. Chromatic CSF, which is a quick and valid index to measure human visual performance and various retinal diseases in two-dimensional (2D) space, can not be directly applied into the measurement of human stereo visual performance. And no existing perception model considers the influence of chromatic CSF of inclined planes on depth perception in three-dimensional (3D) space. The main aim of this research is to extend traditional chromatic contrast sensitivity characteristics to 3D space and build a model applicable in 3D space, for example, strengthening stereo quality of 3D images. This research also attempts to build a vision model or method to check human visual characteristics of stereo blindness. In this paper, CRT screen was clockwise and anti-clockwise rotated respectively to form the inclined planes. Four inclined planes were selected to investigate human chromatic vision in 3D space and contrast threshold of each inclined plane was measured with 18 observers. Stimuli were isoluminant blue-yellow sinusoidal gratings. Horizontal spatial frequencies ranged from 0.05 to 5 c/d. Contrast sensitivity was calculated as the inverse function of the pooled cone contrast threshold. According to the relationship between spatial frequency of inclined plane and horizontal spatial frequency, the chromatic contrast sensitivity characteristics in 3D space have been modeled based on the experimental data. The results show that the proposed model can well predicted human chromatic contrast sensitivity characteristics in 3D space.

THE EFFECT OF BONDING AND SURFACE SEALANT APPLICATION ON POSTOPERATIVE SENSITIVITY FROM POSTERIOR COMPOSITES

Directory of Open Access Journals (Sweden)

Neslihan TEKÇE

2015-10-01

Full Text Available Purpose: The purpose of the study was to evaluate the postoperative sensitivity of posterior Class I composite restoration at short-term, restorated with two different all-in-one self-etch adhesives with or without surface sealant application. Materials and Methods: 44 restorations were inserted in 11 patients who required Class I restorations in their molars. Each patient received 4 restorations, thus four groups were formed; (1 G-Aenial Bond (GC, Japan; (2 Clearfil S3 Bond (Kuraray, Japan; (3 G-Aenial Bond+Fortify Plus (Bisco, USA, (4 Clearfil S3 Bond+Fortify Plus. Sensitivity was evaluated at 24h, 7, 15, and 30 days using cold air, ice, and pressure stimuli using a visual analog scale. Comparisons of continuous variables between the sensitivity evaluations were performed using the Friedman’s One-Way Analysis of Variance with repeated measures test (p0.05. The use of Clearfil S3 Bond resulted in almost the same level of postoperative sensitivity as did the use of G-Aenial Bond. The highest sensitivity scores were observed for the surface sealant applied teeth without any statistical significance (p>0.05. Conclusions: Self etch adhesives displayed postoperative sensitivity. The sensitivity scores slightly decreased at the end of 30 days (p>0.05. Surface sealant application did not result in a decrease in sensitivity scores for either dentin adhesives.

Precise determination of low-Q nucleon electromagnetic form factors and their impact on parity-violating e-p elastic scattering

International Nuclear Information System (INIS)

Arrington, John; Sick, Ingo

2007-01-01

The extraction of the strangeness form factors from parity-violating elastic electron-proton scattering is sensitive to the electromagnetic form factors at low Q 2 . We provide parametrizations for the form factors and uncertainties, including the effects of two-photon exchange corrections to the extracted electromagnetic form factors. We study effect of the correlations between different form factors, in particular as they impact the parity-violating asymmetry and the extraction of the strangeness form factors. We provide a prescription to extract the strangeness form factors from the asymmetry that provides an excellent approximation of the full two-photon correction. The corrected form factors are also appropriate as input for other low-Q analyses, although the effects of correlations and two-photon exchange corrections may be different

High frequency electrical stimulation concurrently induces central sensitization and ipsilateral inhibitory pain modulation.

Science.gov (United States)

Vo, L; Drummond, P D

2013-03-01

In healthy humans, analgesia to blunt pressure develops in the ipsilateral forehead during various forms of limb pain. The aim of the current study was to determine whether this analgesic response is induced by ultraviolet B radiation (UVB), which evokes signs of peripheral sensitization, or by high-frequency electrical stimulation (HFS), which triggers signs of central sensitization. Before and after HFS and UVB conditioning, sensitivity to heat and to blunt and sharp stimuli was assessed at and adjacent to the treated site in the forearm. In addition, sensitivity to blunt pressure was measured bilaterally in the forehead. The effect of ipsilateral versus contralateral temple cooling on electrically evoked pain in the forearm was then examined, to determine whether HFS or UVB conditioning altered inhibitory pain modulation. UVB conditioning triggered signs of peripheral sensitization, whereas HFS conditioning triggered signs of central sensitization. Importantly, ipsilateral forehead analgesia developed after HFS but not UVB conditioning. In addition, decreases in electrically evoked pain at the HFS-treated site were greater during ipsilateral than contralateral temple cooling, whereas decreases at the UVB-treated site were similar during both procedures. HFS conditioning induced signs of central sensitization in the forearm and analgesia both in the ipsilateral forehead and the HFS-treated site. This ipsilateral analgesia was not due to peripheral sensitization or other non-specific effects, as it failed to develop after UVB conditioning. Thus, the supra-spinal mechanisms that evoke central sensitization might also trigger a hemilateral inhibitory pain modulation process. This inhibitory process could sharpen the boundaries of central sensitization or limit its spread. © 2012 European Federation of International Association for the Study of Pain Chapters.

Interactions between motion and form processing in the human visual system

Directory of Open Access Journals (Sweden)

George eMather

2013-05-01

Full Text Available The predominant view of motion and form processing in the human visual system assumes that these two attributes are handled by separate and independent modules. Motion processing involves filtering by direction-selective sensors, followed by integration to solve the aperture problem. Form processing involves filtering by orientation-selective and size-selective receptive fields, followed by integration to encode object shape. It has long been known that motion signals can influence form processing in the well-known Gestalt principle of common fate; texture elements which share a common motion property are grouped into a single contour or texture region. However recent research in psychophysics and neuroscience indicates that the influence of form signals on motion processing is more extensive than previously thought. First, the salience and apparent direction of moving lines depends on how the local orientation and direction of motion combine to match the receptive field properties of motion-selective neurons. Second, orientation signals generated by ‘motion-streaks’ influence motion processing; motion sensitivity, apparent direction and adaptation are affected by simultaneously present orientation signals. Third, form signals generated by human body shape influence biological motion processing, as revealed by studies using point-light motion stimuli. Thus form-motion integration seems to occur at several different levels of cortical processing, from V1 to STS.

Influence of annealing time on pH sensitivity of ZnO sensing membrane for EGFET sensor

Science.gov (United States)

Zulkefle, M. A.; Rahman, R. A.; Yusoff, K. A.; Abdullah, W. F. H.; Rusop, M.; Herman, S. H.

2018-05-01

Solid-state materials have becomes essential in recent technological advancements. This study also utilized solid-state material but in form of thin films to sense hydrogen ions in solutions. Fabrication of ZnO thin film was done using sol-gel spin coating technique. In an attempt to increase the pH sensitivity of the produced film, prolonging of annealing time was done. It was found that the increase in annealing time from 15 minutes to 30 minutes had managed to improve the sensitivity by 4.35%. The optimum pH sensitivity and linearity obtained in this study is 50.40 mV/pH and 0.9911 respectively.

Climate Sensitivity

Energy Technology Data Exchange (ETDEWEB)

Lindzen, Richard [M.I.T.

2011-11-09

Warming observed thus far is entirely consistent with low climate sensitivity. However, the result is ambiguous because the sources of climate change are numerous and poorly specified. Model predictions of substantial warming aredependent on positive feedbacks associated with upper level water vapor and clouds, but models are notably inadequate in dealing with clouds and the impacts of clouds and water vapor are intimately intertwined. Various approaches to measuring sensitivity based on the physics of the feedbacks will be described. The results thus far point to negative feedbacks. Problems with these approaches as well as problems with the concept of climate sensitivity will be described.

Highly sensitive refractive index fiber inline Mach-Zehnder interferometer fabricated by femtosecond laser micromachining and chemical etching

Science.gov (United States)

Sun, Xiao-Yan; Chu, Dong-Kai; Dong, Xin-Ran; Zhou, Chu; Li, Hai-Tao; Luo-Zhi; Hu, You-Wang; Zhou, Jian-Ying; Cong-Wang; Duan, Ji-An

2016-03-01

A High sensitive refractive index (RI) sensor based on Mach-Zehnder interferometer (MZI) in a conventional single-mode optical fiber is proposed, which is fabricated by femtosecond laser transversal-scanning inscription method and chemical etching. A rectangular cavity structure is formed in part of fiber core and cladding interface. The MZI sensor shows excellent refractive index sensitivity and linearity, which exhibits an extremely high RI sensitivity of -17197 nm/RIU (refractive index unit) with the linearity of 0.9996 within the refractive index range of 1.3371-1.3407. The experimental results are consistent with theoretical analysis.

Comparison of the Sensitivity to Change of the 36-Item Short Form Health Survey and the Lupus Quality of Life Measure Using Various Definitions of Minimum Clinically Important Differences in Patients With Active Systemic Lupus Erythematosus.

Science.gov (United States)

Nantes, Stephanie G; Strand, Vibeke; Su, Jiandong; Touma, Zahi

2018-01-01

The Medical Outcomes Study Short Form 36 (SF-36) and Lupus Quality of Life (LupusQoL) are health-related quality of life questionnaires used in systemic lupus erythematosus (SLE). We first determined the hypothesis-testing construct validity of the SF-36 and LupusQoL against disease activity in patients with active SLE and then compared the sensitivity to change of SF-36 and LupusQoL domains according to different definitions of minimum clinically important differences (MCIDs) for improvement and worsening in the current cohort. Seventy-eight clinically active SLE patients concurrently completed both questionnaires at their baseline and followup visits. Questionnaire domain scores were correlated with the SLE Disease Activity Index 2000 (SLEDAI-2K) and evaluated for floor/ceiling effects. The sensitivity to change of domains in each questionnaire was analyzed first, according to the various MCID definitions and, second, by clinically meaningful changes in disease activity. The magnitudes of change in each domain score between the baseline and followup visit were evaluated using standardized response means. In the 78 patients, the mean ± SD SLEDAI-2K scores were 9.7 ± 4.8 at baseline and 8.8 ± 5.1 at followup. SF-36/LupusQoL domain scores did not correlate with disease activity. The SF-36 showed floor effects, and ceiling effects were evident in both questionnaires. All domains of both questionnaires showed sensitivity to change over time. Specific domains that reflected worsening or improvement differed according to differing MCID definitions. In SLE patients with active disease, both the SF-36 and LupusQoL are sensitive to change, reflecting both improvement and worsening. More importantly, the LupusQoL SLE-specific domains (planning, burden to others, body image, and intimate relationships) were largely responsive to change. © 2017, American College of Rheumatology.

INFLUENCE OF MODIFIED BIOFLAVONOIDS UPON EFFECTOR LYMPHOCYTES IN MURINE MODEL OF CONTACT SENSITIVITY

Directory of Open Access Journals (Sweden)

D. Z. Albegova

2015-01-01

Full Text Available Contact sensitivity reaction (CSR to 2,4-dinitrofluorobenzene (DNFB in mice is a model of in vivo immune response, being an experimental analogue to contact dermatitis in humans. CSR sensitization phase begins after primary contact with antigen, lasting for 10-15 days in humans, and 5-7 days, in mice. Repeated skin exposure to the sensitizing substance leads to its recognition and triggering immune inflammatory mechanisms involving DNFB-specific effector T lymphocytes. The CSR reaches its maximum 18-48 hours after re-exposure to a hapten. There is only scarce information in the literature about effects of flavonoids on CSR, including both stimulatory and inhibitory effects. Flavonoids possessed, predominantly, suppressive effects against the CSR development. In our laboratory, a model of contact sensitivity was reproduced in CBA mice by means of cutaneous sensitization by 2,4-dinitrofluorobenzene. The aim of the study was to identify the mechanisms of immunomodulatory action of quercetin dihydrate and modified bioflavonoids, using the method of adoptive transfer contact sensitivity by splenocytes and T-lymphocytes. As shown in our studies, a 30-min pre-treatment of splenocytes and T-lymphocytes from sensitized mice with modified bioflavonoids before the cell transfer caused complete prevention of contact sensitivity reaction in syngeneic recipient mice. Meanwhile, this effect was not associated with cell death induction due to apoptosis or cytotoxicity. Quercetin dihydrate caused only partially suppression the activity of adaptively formed T-lymphocytes, the contact sensitivity effectors. It was shown that the modified bioflavonoid more stronger suppress adoptive transfer of contact sensitivity in comparison with quercetin dehydrate, without inducing apoptosis of effector cells. Thus, the modified bioflavonoid is a promising compound for further studies in a model of contact sensitivity, due to its higher ability to suppress transfer of CSR with

New far infrared images of bright, nearby, star-forming regions

Science.gov (United States)

Harper, D. AL, Jr.; Cole, David M.; Dowell, C. Darren; Lees, Joanna F.; Lowenstein, Robert F.

1995-01-01

Broadband imaging in the far infrared is a vital tool for understanding how young stars form, evolve, and interact with their environment. As the sensitivity and size of detector arrays has increased, a richer and more detailed picture has emerged of the nearest and brightest regions of active star formation. We present data on M 17, M 42, and S 106 taken recently on the Kuiper Airborne Observatory with the Yerkes Observatory 60-channel far infrared camera, which has pixel sizes of 17 in. at 60 microns, 27 in. at 100 microns, and 45 in. at 160 and 200 microns. In addition to providing a clearer view of the complex central cores of the regions, the images reveal new details of the structure and heating of ionization fronts and photodissociation zones where radiation form luminous stars interacts with adjacent molecular clouds.

Comparison of various methods of detection of different forms of dengue virus type 2 RNA in cultured cells

International Nuclear Information System (INIS)

Liu, H.S.; Lin, Y.L.; Chen, C.C.

1997-01-01

In this report, the sensitivity of various methods of detection of dengue virus type 2 (DEN-2) sense, antisense, replicative intermediate (RI) and replicative form (RF) RNAs in infected mosquito Aedes pseudoscutellaris AP-61 and mammalian baby hamster kidney BHK-21 cells is compared. LiCl precipitation was used for separation of viral RF RNA from RI RNA. Our results show that reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and slot blot hybridisation of LiCl-fractionated RNA were the most sensitive methods of detection of viral RNA and determination of its single-stranded form. Northern blot analysis was the least sensitive method of detection of any form of viral RNA. U sing slot blot hybridisation of LiCl-precipitated RNA, viral RI RNA containing de novo synthesised negative strand viral RNA was first detected 30 min after virus inoculation in both cell lines. This is the earliest time of detection of DEN viral RNA synthesis in host cells so far reported. However, RF RNA could not be detected until 24 hrs post infection (p.i.) in AP-61 and 2 days p.i. in BHK-21 cells, respectively. The sequential order of individual forms of viral RNA detected in the infected cells was RI, RF and genomic RNAs. Viral RNA was detected in AP-61 cells always earlier than in BHK-21 cells. Moreover, the level of viral RNA in AP-61 cells was higher than that in BHK-21 cells, suggesting that the virus replicated more actively in AP-61 cells. In conclusion, the LiCl separation of viral RNA followed by slot blot hybridisation was found to be the most sensitive and reliable method of detection of DEN virus RI, RF and genomic RNAs in the infected cells. Moreover, this method can be applied to determine the replication status of any single-stranded RNA virus in the host. (authors)

Application of perturbation methods and sensitivity analysis to water hammer problems in hydraulic networks

International Nuclear Information System (INIS)

Balino, Jorge L.; Larreteguy, Axel E.; Andrade Lima, Fernando R.

1995-01-01

The differential method was applied to the sensitivity analysis for water hammer problems in hydraulic networks. Starting from the classical water hammer equations in a single-phase liquid with friction, the state vector comprising the piezometric head and the velocity was defined. Applying the differential method the adjoint operator, the adjoint equations with the general form of their boundary conditions, and the general form of the bilinear concomitant were calculated. The discretized adjoint equations and the corresponding boundary conditions were programmed and solved by using the so called method of characteristics. As an example, a constant-level tank connected through a pipe to a valve discharging to atmosphere was considered. The bilinear concomitant was calculated for this particular case. The corresponding sensitivity coefficients due to the variation of different parameters by using both the differential method and the response surface generated by the computer code WHAT were also calculated. The results obtained with these methods show excellent agreement. (author). 11 refs, 2 figs, 2 tabs

Defining and detecting structural sensitivity in biological models: developing a new framework.

Science.gov (United States)

Adamson, M W; Morozov, A Yu

2014-12-01

When we construct mathematical models to represent biological systems, there is always uncertainty with regards to the model specification--whether with respect to the parameters or to the formulation of model functions. Sometimes choosing two different functions with close shapes in a model can result in substantially different model predictions: a phenomenon known in the literature as structural sensitivity, which is a significant obstacle to improving the predictive power of biological models. In this paper, we revisit the general definition of structural sensitivity, compare several more specific definitions and discuss their usefulness for the construction and analysis of biological models. Then we propose a general approach to reveal structural sensitivity with regards to certain system properties, which considers infinite-dimensional neighbourhoods of the model functions: a far more powerful technique than the conventional approach of varying parameters for a fixed functional form. In particular, we suggest a rigorous method to unearth sensitivity with respect to the local stability of systems' equilibrium points. We present a method for specifying the neighbourhood of a general unknown function with [Formula: see text] inflection points in terms of a finite number of local function properties, and provide a rigorous proof of its completeness. Using this powerful result, we implement our method to explore sensitivity in several well-known multicomponent ecological models and demonstrate the existence of structural sensitivity in these models. Finally, we argue that structural sensitivity is an important intrinsic property of biological models, and a direct consequence of the complexity of the underlying real systems.

Radioimmunoassay for free and bound forms of abscisic acid

Energy Technology Data Exchange (ETDEWEB)

Cutting, J.G.; Hofman, P.J.; Wolstenholme, B.N. (Natal Univ., Pietermaritzburg (South Africa). Dept. of Horticultural Science); Lishman, A.W. (Natal Univ., Pietermaritzburg (South Africa). Dept. of Animal Science)

1984-01-01

A radioimmunoassay (RIA) for the quanitation of abscisic acid (ABA) has been developed. The assay is extremely sensitive and measuring ranges extend from 10 pg to 10 ng. Although the assay was free of contaminant interference when applied to avocado material, crude extract analysis yielded a composite of free and bound forms of ABA. Equivalents of 20 mg of plant material were spotted onto silica gel plates (GF/sup 245/ solvent:toluene:ethyl acetate : acetic acid 25:15:3), developed and the relative Rf zones removed and subjected to RIA. The technique was tested on avocados.

Biomarkers of Sensitivity and Exposure in Washington State Pesticide Handlers

Science.gov (United States)

Keifer, M.C.; Checkoway, H.; De Roos, A.J.; Farin, F.M.; Fenske, R.A.; Richter, R.J.; van Belle, G.; Furlong, C.E.

2011-01-01

Organophosphate (OP) and N-methyl-carbamate (CB) insecticides are widely used in agriculture in the US and abroad. These compounds – which inhibit acetylcholinesterase (AChE) enzyme activity – continue to be responsible for a high proportion of pesticide poisonings among US agricultural workers. It is possible that some individuals may be especially susceptible to health effects related to OP/CB exposure. The paraoxonase (PON1) enzyme metabolizes the highly toxic oxon forms of some OPs, and an individual's PON1 status may be an important determinant of his or her sensitivity to these chemicals. This chapter discusses methods used to characterize individual PON1 status and reviews previous epidemiologic studies that have evaluated PON1-related sensitivity to OPs in relation to various health endpoints. It also describes an ongoing longitudinal study among OP-exposed agricultural pesticide handlers who are participating in a recently implemented cholinesterase monitoring program in Washington State. This study will evaluate handlers' PON1 status as a hypothesized determinant of butyrylcholinesterase (BuChE) inhibition. Such studies will be useful to determine how regulatory risk assessments might account for differences in PON1-related OP sensitivity when characterizing inter-individual variability in risk related to OP exposure. Recent work assessing newer and more sensitive biomarkers of OP exposure is also discussed briefly in this chapter. PMID:20221867

Sensitivity and Specificity of Clinical and Laboratory Otolith Function Tests.

Science.gov (United States)

Kumar, Lokesh; Thakar, Alok; Thakur, Bhaskar; Sikka, Kapil

2017-10-01

To evaluate clinic based and laboratory tests of otolith function for their sensitivity and specificity in demarcating unilateral compensated complete vestibular deficit from normal. Prospective cross-sectional study. Tertiary care hospital vestibular physiology laboratory. Control group-30 healthy adults, 20-45 years age; Case group-15 subjects post vestibular shwannoma excision or post-labyrinthectomy with compensated unilateral complete audio-vestibular loss. Otolith function evaluation by precise clinical testing (head tilt test-HTT; subjective visual vertical-SVV) and laboratory testing (headroll-eye counterroll-HR-ECR; vesibular evoked myogenic potentials-cVEMP). Sensitivity and specificity of clinical and laboratory tests in differentiating case and control subjects. Measurable test results were universally obtained with clinical otolith tests (SVV; HTT) but not with laboratory tests. The HR-ECR test did not indicate any definitive wave forms in 10% controls and 26% cases. cVEMP responses were absent in 10% controls.HTT test with normative cutoff at 2 degrees deviations from vertical noted as 93.33% sensitive and 100% specific. SVV test with normative cutoff at 1.3 degrees noted as 100% sensitive and 100% specific. Laboratory tests demonstrated poorer specificities owing primarily to significant unresponsiveness in normal controls. Clinical otolith function tests, if conducted with precision, demonstrate greater ability than laboratory testing in discriminating normal controls from cases with unilateral complete compensated vestibular dysfunction.

New and highly sensitive assay for L-5-hydroxytryptophan decarboxylase activity by high-performance liquid chromatography-voltammetry.

Science.gov (United States)

Rahman, M K; Nagatsu, T; Kato, T

1980-12-12

This paper describes a new, inexpensive and highly sensitive assay for aromatic L-amino acid decarboxylase (AADC) activity, using L-5-hydroxytryptophan (L-5-HTP) as substrate, in rat and human brains and serum by high-performance liquid chromatography (HPLC) with voltammetric detection. L-5-HTP was used as substrate and D-5-HTP for the blank. After isolating serotonin (5-HT) formed enzymatically from L-5-HTP on a small Amberlite CG-50 column, the 5-HT was eluted with hydrochloric acid and assayed by HPLC with a voltammetric detector. N-Methyldopamine was added to each incubation mixture as an internal standard. This method is sensitive enough to measure 5-HT, formed by the enzyme, 100 fmol to 140 pmol or more. An advantage of this method is that one can incubate the enzyme for longer time (up to 150 min), as compared with AADC assay using L-DOPA as substrate, resulting in a very high sensitivity. By using this new method, AADC activity was discovered in rat serum.

Effect of preliminary annealing of silicon substrates on the spectral sensitivity of photodetectors in bipolar integrated circuits

International Nuclear Information System (INIS)

Blynskij, V.I.; Bozhatkin, O.A.; Golub, E.S.; Lemeshevskaya, A.M.; Shvedov, S.V.

2010-01-01

We examine the results of an effect of preliminary annealing on the spectral sensitivity of photodetectors in bipolar integrated circuits, formed in silicon grown by the Czochralski method. We demonstrate the possibility of substantially improving the sensitivity of photodetectors in the infrared region of the spectrum with twostep annealing. The observed effect is explained by participation of oxidation in the gettering process, where oxidation precedes formation of a buried n + layer in the substrate. (authors)

Improving the forming capability of laser dynamic forming by using rubber as a forming medium

Science.gov (United States)

Shen, Zongbao; Liu, Huixia; Wang, Xiao; Wang, Cuntang

2016-04-01

Laser dynamic forming (LDF) is a novel high velocity forming technique, which employs laser-generated shock wave to load the sample. The forming velocity induced by the high energy laser pulse may exceed the critical forming velocity, resulting in the occurrence of premature fracture. To avoid the above premature fracture, rubber is introduced in LDF as a forming medium to prolong the loading duration in this paper. Laser induced shock wave energy is transferred to the sample in different forming stages, so the forming velocity can be kept below the critical forming velocity when the initial laser energy is high for fracture. Bulge forming experiments with and without rubber were performed to study the effect of rubber on loading duration. The experimental results show that, the shock wave energy attenuates during the propagation through the rubber layer, the rubber can avoid the premature fracture. So the plastic deformation can continue, the forming capability of LDF is improved. Due to the severe plastic deformation under rubber compression, adiabatic shear bands (ASB) occur in LDF with rubber. The material softening in ASB leads to the irregular fracture, which is different from the premature fracture pattern (regular fracture) in LDF without rubber. To better understand this deformation behavior, Johnson-Cook model is used to simulate the dynamic response and the evolution of ASB of copper sample. The simulation results also indicate the rubber can prolong the loading duration.

Highly Sensitive Flexible Magnetic Sensor Based on Anisotropic Magnetoresistance Effect.

Science.gov (United States)

Wang, Zhiguang; Wang, Xinjun; Li, Menghui; Gao, Yuan; Hu, Zhongqiang; Nan, Tianxiang; Liang, Xianfeng; Chen, Huaihao; Yang, Jia; Cash, Syd; Sun, Nian-Xiang

2016-11-01

A highly sensitive flexible magnetic sensor based on the anisotropic magnetoresistance effect is fabricated. A limit of detection of 150 nT is observed and excellent deformation stability is achieved after wrapping of the flexible sensor, with bending radii down to 5 mm. The flexible AMR sensor is used to read a magnetic pattern with a thickness of 10 μm that is formed by ferrite magnetic inks. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Prediction of remission in Graves' disease after thionamide therapy by technetium-99m early uptake

International Nuclear Information System (INIS)

Misaki, Takashi; Dokoh, Shigeharu; Koh, Toshikiyo; Shimbo, Shin-ichiro; Hidaka, Akinari; Iida, Yasuhiro; Kasagi, Kanji; Konishi, Junji.

1991-01-01

In the clinical management of Graves' thyrotoxicosis, one of the most important subject is when to stop antithyroid drugs after achieving an euthyroid state. T 3 suppression test and other methods have been used to forecast the outcome after drug cessation, but the results were not always satisfactory. We have attempted to predict remission of Graves' disease by single measurement of early technetium uptake without administration of triiodothyronine. Drugs were discontinued in the seventy-five patients with Graves' disease on maintenance doses of either methimazole or propylthiouracil who showed normalized uptake (4.0% or less). Of 64 patients evaluable after twelve months, 55 (86%) remained euthyroid, 8 relapsed, and 1 became hypothyoid. With its accuracy in prediction of short-term remission comparable or superior to T 3 suppression test, this rapid and simple method seemed suitable for routine use in clinical practice. (author)

NGVLA Observations of Dense Gas Filaments in Star-Forming Regions

Science.gov (United States)

Di Francesco, James; Chen, Mike; Keown, Jared; GAS Team, KEYSTONE Team

2018-01-01

Recent observations of continuum emission from nearby star-forming regions with Herschel and JCMT have revealed that filaments are ubiquitous structures within molecular clouds. Such filaments appear to be intimately connected to star formation, with those having column densities of AV > 8 hosting the majority of prestellar cores and young protostars in clouds. Indeed, this “threshold” can be explained simply as the result of supercritical cylinder fragmentation. How specifically star-forming filaments form in molecular clouds, however, remains unclear, though gravity and turbulence are likely involved. Observations of their kinematics are needed to understand how mass flows both onto and through these filaments. We show here results from two recent surveys, the Green Bank Ammonia Survey (GAS) and the K-band Examinations of Young Stellar Object Natal Environments (KEYSTONE) that have used the Green Bank Telescope’s K-band Focal Plane Array instrument to map NH3 (1,1) emission from dense gas in nearby star-forming regions. Data from both surveys show that NH3 emission traces extremely well the high column density gas across these star-forming regions. In particular, the GAS results for NGC 1333 show NH3-based velocity gradients either predominantly parallel or perpendicular to the filament spines. Though the GAS and KEYSTONE data are vital for probing filaments, higher resolutions than possible with the GBT alone are needed to examine the kinematic patterns on the 0.1-pc scales of star-forming cores within filaments. We describe how the Next Generation Very Large Array (NGVLA) will uniquely provide the key wide-field data of high sensitivity needed to explore how ambient gas in molecular clouds forms filaments that evolve toward star formation.

Divergent methylation pattern in adult stage between two forms of Tetranychus urticae (Acari: Tetranychidae).

Science.gov (United States)

Yang, Si-Xia; Guo, Chao; Zhao, Xiu-Ting; Sun, Jing-Tao; Hong, Xiao-Yue

2017-02-19

The two-spotted spider mite, Tetranychus urticae Koch has two forms: green form and red form. Understanding the molecular basis of how these two forms established without divergent genetic background is an intriguing area. As a well-known epigenetic process, DNA methylation has particularly important roles in gene regulation and developmental variation across diverse organisms that do not alter genetic background. Here, to investigate whether DNA methylation could be associated with different phenotypic consequences in the two forms of T. urticae, we surveyed the genome-wide cytosine methylation status and expression level of DNA methyltransferase 3 (Tudnmt3) throughout their entire life cycle. Methylation-sensitive amplification polymorphism (MSAP) analyses of 585 loci revealed variable methylation patterns in the different developmental stages. In particular, principal coordinates analysis (PCoA) indicates a significant epigenetic differentiation between female adults of the two forms. The gene expression of Tudnmt3 was detected in all examined developmental stages, which was significantly different in the adult stage of the two forms. Together, our results reveal the epigenetic distance between the two forms of T. urticae, suggesting that DNA methylation might be implicated in different developmental demands, and contribute to different phenotypes in the adult stage of these two forms. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Environmental Sensitivity in Children: Development of the Highly Sensitive Child Scale and Identification of Sensitivity Groups

Science.gov (United States)

Pluess, Michael; Assary, Elham; Lionetti, Francesca; Lester, Kathryn J.; Krapohl, Eva; Aron, Elaine N.; Aron, Arthur

2018-01-01

A large number of studies document that children differ in the degree they are shaped by their developmental context with some being more sensitive to environmental influences than others. Multiple theories suggest that "Environmental Sensitivity" is a common trait predicting the response to negative as well as positive exposures.…

Defining Biological Networks for Noise Buffering and Signaling Sensitivity Using Approximate Bayesian Computation

Directory of Open Access Journals (Sweden)

Shuqiang Wang

2014-01-01

Full Text Available Reliable information processing in cells requires high sensitivity to changes in the input signal but low sensitivity to random fluctuations in the transmitted signal. There are often many alternative biological circuits qualifying for this biological function. Distinguishing theses biological models and finding the most suitable one are essential, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model. Here, we employ the approximate Bayesian computation (ABC method based on sequential Monte Carlo (SMC to search for biological circuits that can maintain signaling sensitivity while minimizing noise propagation, focusing on cases where the noise is characterized by rapid fluctuations. By systematically analyzing three-component circuits, we rank these biological circuits and identify three-basic-biological-motif buffering noise while maintaining sensitivity to long-term changes in input signals. We discuss in detail a particular implementation in control of nutrient homeostasis in yeast. The principal component analysis of the posterior provides insight into the nature of the reaction between nodes.

Quarternary structure and enzymological properties of the different hormone-sensitive lipase (HSL) isoforms

DEFF Research Database (Denmark)

Krintel, Christian; Klint, Cecilia; Lindvall, Håkan

2010-01-01

Hormone-sensitive lipase (HSL) is a key enzyme in the mobilization of energy in the form of fatty acids from intracellular stores of neutral lipids. The enzyme has been shown to exist in different isoforms with different molecular masses (84 kDa, 89 kDa and 117 kDa) expressed in a tissue-dependen...

THE PRESENCE OF A B SUBUNIT INCREASES SENSITIVITY OF SODIUM CHANNEL NAV1.3, BUT NOT NAV1.2, TO TYPE II PYRETHROIDS.

Science.gov (United States)

Voltage-sensitive sodium channels (VSSCs) are a primary target of pyrethroid insecticides. VSSCs are comprised of a pore-forming ¿ and auxillary ß subunits, and multiple isoforms of both subunit types exist. The sensitivity of different isoform combinations to pyrethroids has not...

Solvent sensitivity of smart 3D-printed nanocomposite liquid sensor

Science.gov (United States)

Aliheidari, Nahal; Ameli, Amir; Pötschke, Petra

2018-03-01

Fused deposition modeling (FDM) is one of the 3D printing methods that has attracted significant attention. In this method, small and complex samples with nearly no limitation in geometry can be fabricated layer by layer to form end-use parts. This work investigates the liquid sensing behavior of FDM printed flexible thermoplastic polyurethane, TPU filled with multiwalled carbon nanotubes, MWCNTs. The sensing capability of printed TPU-MWCNT was studied as a function of MWCNT content and infill density in response to different solvents, i.e., ethanol, acetone and toluene. The solvents were selected based on their widespread use and importance in medical and industrial applications. U-shaped liquid sensors with 2, 3 and 4wt.% MWCNT content were printed at three different infill densities of 50, 75 and 100%. Solvent sensitivity was then characterized by immersing the sensors in the solvents and measuring the resistance evolution over 25s. The results indicated a sensitivity order of acetone > toluene > ethanol, which was in agreement with the predictions of FloryHiggins solubility equation. For all the solvents, the sensitivity was enhanced as the infill density of the printed samples was decreased. This was attributed to the increased surface area to volume ratio and shortened diffusion paths. The MWCNT content was also observed to have a profound effect on the sensitivity; in samples with partial infill, the sensitivity was found to be inversely proportional to the MWCNT content, such that the highest resistance change was obtained for nanocomposites with the lowest MWCNT content of 2wt.%. For instance, a resistance increase of more than 10 times was obtained in 25 s once TPU-2wt.%MWCNT with 50% infill was tested against acetone. The results of this work reveals that highly sensitive liquid sensors can be fabricated with the aid of 3D printing without the need for complex processing methods.

An analysis of students’ cognitive structures in relation to their environmental sensitivity

Directory of Open Access Journals (Sweden)

Gercek Cem

2017-01-01

Full Text Available One of the basic aims of environment-related subjects included in the biology curriculum is to raise environmental awareness. Yet, the fact that the concepts taught especially in the context of environmental issues are abstract influences meaningful learning. This, in turn, influences behaviours displayed. Exhibiting students’ cognitive structures in assuring effective and meaningful concept teaching increases the importance of studies conducted. Unavailability of studies in the literature analysing students’ cognitive structures in relation to their sensitivity to the environment demonstrates the importance of this current study. This study aims to analyse students’ cognitive structures in relation to their environmental sensitivity. The study employs survey model- one of the qualitative research designs. The study group was composed of 56 high school students in the 2016-2017 academic year. The study group was formed through purposeful sampling. Word Association Test (WAT was prepared in order to uncover students’ cognitive structures in relation to their environmental sensitivity. Having transcribed the data obtained, they were put to content analysis and were transferred to the medium of computer. The results showed that students’ cognitive structure concerning their environmental sensitivity was divided into categories.

Photo-EMF Sensitivity of Porous Silicon Thin Layer–Crystalline Silicon Heterojunction to Ammonia Adsorption

Directory of Open Access Journals (Sweden)

Kae Dal Kwack

2011-01-01

Full Text Available A new method of using photo-electromotive force in detecting gas and controlling sensitivity is proposed. Photo-electromotive force on the heterojunction between porous silicon thin layer and crystalline silicon wafer depends on the concentration of ammonia in the measurement chamber. A porous silicon thin layer was formed by electrochemical etching on p-type silicon wafer. A gas and light transparent electrical contact was manufactured to this porous layer. Photo-EMF sensitivity corresponding to ammonia concentration in the range from 10 ppm to 1,000 ppm can be maximized by controlling the intensity of illumination light.

Photo-EMF sensitivity of porous silicon thin layer-crystalline silicon heterojunction to ammonia adsorption.

Science.gov (United States)

Vashpanov, Yuriy; Jung, Jae Il; Kwack, Kae Dal

2011-01-01

A new method of using photo-electromotive force in detecting gas and controlling sensitivity is proposed. Photo-electromotive force on the heterojunction between porous silicon thin layer and crystalline silicon wafer depends on the concentration of ammonia in the measurement chamber. A porous silicon thin layer was formed by electrochemical etching on p-type silicon wafer. A gas and light transparent electrical contact was manufactured to this porous layer. Photo-EMF sensitivity corresponding to ammonia concentration in the range from 10 ppm to 1,000 ppm can be maximized by controlling the intensity of illumination light.

Photo-EMF Sensitivity of Porous Silicon Thin Layer–Crystalline Silicon Heterojunction to Ammonia Adsorption

Science.gov (United States)

Vashpanov, Yuriy; Jung, Jae Il; Kwack, Kae Dal

2011-01-01

A new method of using photo-electromotive force in detecting gas and controlling sensitivity is proposed. Photo-electromotive force on the heterojunction between porous silicon thin layer and crystalline silicon wafer depends on the concentration of ammonia in the measurement chamber. A porous silicon thin layer was formed by electrochemical etching on p-type silicon wafer. A gas and light transparent electrical contact was manufactured to this porous layer. Photo-EMF sensitivity corresponding to ammonia concentration in the range from 10 ppm to 1,000 ppm can be maximized by controlling the intensity of illumination light. PMID:22319353

First order sensitivity analysis of flexible multibody systems using absolute nodal coordinate formulation

International Nuclear Information System (INIS)

Pi Ting; Zhang Yunqing; Chen Liping

2012-01-01

Design sensitivity analysis of flexible multibody systems is important in optimizing the performance of mechanical systems. The choice of coordinates to describe the motion of multibody systems has a great influence on the efficiency and accuracy of both the dynamic and sensitivity analysis. In the flexible multibody system dynamics, both the floating frame of reference formulation (FFRF) and absolute nodal coordinate formulation (ANCF) are frequently utilized to describe flexibility, however, only the former has been used in design sensitivity analysis. In this article, ANCF, which has been recently developed and focuses on modeling of beams and plates in large deformation problems, is extended into design sensitivity analysis of flexible multibody systems. The Motion equations of a constrained flexible multibody system are expressed as a set of index-3 differential algebraic equations (DAEs), in which the element elastic forces are defined using nonlinear strain-displacement relations. Both the direct differentiation method and adjoint variable method are performed to do sensitivity analysis and the related dynamic and sensitivity equations are integrated with HHT-I3 algorithm. In this paper, a new method to deduce system sensitivity equations is proposed. With this approach, the system sensitivity equations are constructed by assembling the element sensitivity equations with the help of invariant matrices, which results in the advantage that the complex symbolic differentiation of the dynamic equations is avoided when the flexible multibody system model is changed. Besides that, the dynamic and sensitivity equations formed with the proposed method can be efficiently integrated using HHT-I3 method, which makes the efficiency of the direct differentiation method comparable to that of the adjoint variable method when the number of design variables is not extremely large. All these improvements greatly enhance the application value of the direct differentiation

The relationship between the anoxic sensitivity and the extent of sensitization by nitrous oxide

International Nuclear Information System (INIS)

Ewing, D.; Walton, H.L.; Guilfoil, D.S.; Ohm, M.B.

1991-01-01

Nitrous oxide reacts during irradiation to increase the yield of ·OH, a radical many believe to be a major cause of lethality. Logically, one would expect N 2 O to be a radiation sensitizer. In some instances it is, while in others it is not. In some cases we can explain why N 2 O fails to sensitize; factors such as dose rate, cell concentration, buffer composition and ionic strength all influence when N 2 O will sensitize and if it sensitizes, by what magnitude. Based on the results presented here with multiple strains of procaryotic and eucaryotic cells, we believe the anoxic sensitivity is another critical factor that governs whether N 2 O will sensitize. Our data, with data from the literature, show a relationship between the anoxic sensitivity and the N 2 O enhancement ratio. N 2 O does not sensitize in vitro unless the anoxic sensitivity (inactivation constant, K) is less than ∼ 0.2 daGy -1 . (author)

Investigation of the Sensitivity of Transmission Raman Spectroscopy for Polymorph Detection in Pharmaceutical Tablets.

Science.gov (United States)

Feng, Hanzhou; Bondi, Robert W; Anderson, Carl A; Drennen, James K; Igne, Benoît

2017-08-01

Polymorph detection is critical for ensuring pharmaceutical product quality in drug substances exhibiting polymorphism. Conventional analytical techniques such as X-ray powder diffraction and solid-state nuclear magnetic resonance are utilized primarily for characterizing the presence and identity of specific polymorphs in a sample. These techniques have encountered challenges in analyzing the constitution of polymorphs in the presence of other components commonly found in pharmaceutical dosage forms. Laborious sample preparation procedures are usually required to achieve satisfactory data interpretability. There is a need for alternative techniques capable of probing pharmaceutical dosage forms rapidly and nondestructively, which is dictated by the practical requirements of applications such as quality monitoring on production lines or when quantifying product shelf lifetime. The sensitivity of transmission Raman spectroscopy for detecting polymorphs in final tablet cores was investigated in this work. Carbamazepine was chosen as a model drug, polymorph form III is the commercial form, whereas form I is an undesired polymorph that requires effective detection. The concentration of form I in a direct compression tablet formulation containing 20% w/w of carbamazepine, 74.00% w/w of fillers (mannitol and microcrystalline cellulose), and 6% w/w of croscarmellose sodium, silicon dioxide, and magnesium stearate was estimated using transmission Raman spectroscopy. Quantitative models were generated and optimized using multivariate regression and data preprocessing. Prediction uncertainty was estimated for each validation sample by accounting for all the main variables contributing to the prediction. Multivariate detection limits were calculated based on statistical hypothesis testing. The transmission Raman spectroscopic model had an absolute prediction error of 0.241% w/w for the independent validation set. The method detection limit was estimated at 1.31% w/w. The

Relationship between intrinsic radiation sensitivity and metastatic potential

International Nuclear Information System (INIS)

Lewis, Anne M.; Mei, Su; Doty, Jay; Chen Yi; Pardo, Francisco S.

1996-01-01

Purpose: Prior studies emphasized genetic modulation of tumorigenicity, and experimental metastatic potential in cells transfected with oncogenes. Whether the intrinsic radiation sensitivity of cells might correlate with parallel changes in metastatic potential is unknown. Methods and Materials: Rat embryo cells (REC) were transfected with the following oncogenes, and where appropriate, with corresponding selection markers: pCMV neopEJ6.6ras, pEJ6.6ras/v-myc, pE1a, and pEJ6-.6ras/E1a. Individual transfectant clones and corresponding pooled cellular populations were propagated in selective medium. In vitro cellular radiation sensitivity was determined via clonogenic assays, a minimum of three, by standard techniques and individual SF 2 and MID parameters determined. Tumorigenicity was defined as the number of tumors forming following the injection of 1 x 10 5 - 1 x 10 6 cells into the axillary pouch of three different strains of immune-deficient mice. Animals were killed once resultant tumors reached a maximum size of 1.5-2.0 cm in maximum diameter. For determination of experimental metastatic potential, between 1 x 10 5 -1 x 10 6 cells were injected into the tail veins of litter-matched sibling mice in parallel to the tumorigenicity studies. Results: Radiobiologic studies indicate similar levels of radiation sensitivity among REC, mock-transfected REC, E1a, and combined E1a/ras transfectants. pEJ6.6ras, and combined ras/myc transfected pooled cellular populations demonstrated increases in radiation resistance when compared to the pooled radiobiologic data from untransfected and mock-transfected corresponding pooled cellular populations (p 2 , MID). Rat embryo cells, E1a, and mock-transfectants were relatively radiation sensitive and nontumorigenic. pE1a/ras was tumorigenic but demonstrated relatively low experimental metastatic potential. Ras, and ras/myc transfectants, demonstrated similar levels of experimental metastatic potential on lung colonization assays

The adjoint sensitivity method, a contribution to the code uncertainty evaluation

International Nuclear Information System (INIS)

Ounsy, A.; Crecy, F. de; Brun, B.

1993-01-01

The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs

The adjoint sensitivity method. A contribution to the code uncertainty evaluation

International Nuclear Information System (INIS)

Ounsy, A.; Brun, B.

1993-01-01

The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs

The adjoint sensitivity method. A contribution to the code uncertainty evaluation

Energy Technology Data Exchange (ETDEWEB)

Ounsy, A; Brun, B

1994-12-31

The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs.

The adjoint sensitivity method, a contribution to the code uncertainty evaluation

Energy Technology Data Exchange (ETDEWEB)

Ounsy, A; Crecy, F de; Brun, B

1994-12-31

The application of the ASM (Adjoint Sensitivity Method) to thermohydraulic codes, is examined. The advantage of the method is to be very few CPU time consuming in comparison with usual approach requiring one complete code run per sensitivity determination. The mathematical aspects of the problem are first described, and the applicability of the method of the functional-type response of a thermalhydraulic model is demonstrated. On a simple example of non linear hyperbolic equation (Burgers equation) the problem has been analyzed. It is shown that the formalism used in the literature treating this subject is not appropriate. A new mathematical formalism circumventing the problem is proposed. For the discretized form of the problem, two methods are possible: the Continuous ASM and the Discrete ASM. The equivalence of both methods is demonstrated; nevertheless only the DASM constitutes a practical solution for thermalhydraulic codes. The application of the DASM to the thermalhydraulic safety code CATHARE is then presented for two examples. They demonstrate that ASM constitutes an efficient tool for the analysis of code sensitivity. (authors) 7 figs., 5 tabs., 8 refs.

The guanylyl cyclase family at Y2K.

Science.gov (United States)

Wedel, B; Garbers, D

2001-01-01

During the 1980s the purification, cloning, and expression of various forms of guanylyl cyclase (GC) revealed that they served as receptors for extracellular signals. Seven membrane forms, which presumably exist as homodimers, and four subunits of apparent heterodimers (commonly referred to as the soluble forms) are known, but in animals such as nematodes, much larger numbers of GCs are expressed. The number of transmembrane segments (none, one, or multiple) divide the GC family into three groups. Those with no or one transmembrane segment bind nitric oxide/carbon monoxide (NO/CO) or peptides. There are no known ligands for the multiple transmembrane segment class of GCs. Mutational and structural analyses support a model where catalysis requires a shared substrate binding site between the subunits, whether homomeric or heteromeric in nature. Because some cyclases or cyclase ligand genes lack specific GC inhibitors, disruption of either has been used to define the functions of individual cyclases, as well as to define human genetic disease counterparts.

Structural insights into the cofactor-assisted substrate recognition of yeast methylglyoxal/isovaleraldehyde reductase Gre2.

Science.gov (United States)

Guo, Peng-Chao; Bao, Zhang-Zhi; Ma, Xiao-Xiao; Xia, Qingyou; Li, Wei-Fang

2014-09-01

Saccharomyces cerevisiae Gre2 (EC1.1.1.283) serves as a versatile enzyme that catalyzes the stereoselective reduction of a broad range of substrates including aliphatic and aromatic ketones, diketones, as well as aldehydes, using NADPH as the cofactor. Here we present the crystal structures of Gre2 from S. cerevisiae in an apo-form at 2.00Å and NADPH-complexed form at 2.40Å resolution. Gre2 forms a homodimer, each subunit of which contains an N-terminal Rossmann-fold domain and a variable C-terminal domain, which participates in substrate recognition. The induced fit upon binding to the cofactor NADPH makes the two domains shift toward each other, producing an interdomain cleft that better fits the substrate. Computational simulation combined with site-directed mutagenesis and enzymatic activity analysis enabled us to define a potential substrate-binding pocket that determines the stringent substrate stereoselectivity for catalysis. Copyright © 2014 Elsevier B.V. All rights reserved.

The effect of ethics training on students recognizing ethical violations and developing moral sensitivity.

Science.gov (United States)

Baykara, Zehra Gocmen; Demir, Sevil Guler; Yaman, Sengul

2015-09-01

Moral sensitivity is a life-long cognitive ability. It is expected that nurses who work in a professional purpose at "curing human beings" should have a highly developed moral sensitivity. The general opinion is that ethics education plays a significant role in this sense to enhance the moral sensitivity in terms of nurses' professional behaviors and distinguish ethical violations. This study was conducted as intervention research for the purpose of determining the effect of the ethics training on fourth-year students of the nursing department recognizing ethical violations experienced in the hospital and developing ethical sensitivity. The study was conducted with 50 students, with 25 students each in the experiment and control groups. Students in the experiment group were provided ethics training and consultancy services. The data were collected through the data collection form, which consists of questions on the socio-demographic characteristics and ethical sensitivity of the students, Moral Sensitivity Questionnaire, and the observation form on ethical principle violations/protection in the clinic environment. The data were digitized on the computer with the SPSS for Windows 13.0 program. The data were evaluated utilizing number, percentile calculation, paired samples t-test, Wilcoxon test, and the McNemar test. The total Moral Sensitivity Questionnaire pre-test score averages of students in the experiment group were determined to be 93.88 ± 13.57, and their total post-test score averages were determined to be 89.24 ± 15.90. The total pre-test score averages of students in the control group were determined to be 91.48 ± 17.59, and their total post-test score averages were determined to be 97.72 ± 19.91. In the study, it was determined that the post-training ethical sensitivity of students in the experiment group increased; however, this was statistically not significant. Furthermore, it was determined that the number of ethical principle protection

pH and temperature dual-sensitive liposome gel based on novel cleavable mPEG-Hz-CHEMS polymeric vaginal delivery system

Directory of Open Access Journals (Sweden)

Chen D

2012-05-01

Full Text Available Daquan Chen,1,2 Kaoxiang Sun,1,2 Hongjie Mu,1 Mingtan Tang,3 Rongcai Liang,1,2 Aiping Wang,1,2 Shasha Zhou,1 Haijun Sun,1 Feng Zhao,1 Jianwen Yao,1 Wanhui Liu1,21School of Pharmacy, Yantai University, 2State Key Laboratory of Longacting and Targeting Drug Delivery Systems, Yantai, 3School of Pharmaceutical Sciences, Shandong University, Jinan, People's Republic of ChinaBackground: In this study, a pH and temperature dual-sensitive liposome gel based on a novel cleavable hydrazone-based pH-sensitive methoxy polyethylene glycol 2000-hydrazone-cholesteryl hemisuccinate (mPEG-Hz-CHEMS polymer was used for vaginal administration.Methods: The pH-sensitive, cleavable mPEG-Hz-CHEMS was designed as a modified pH-sensitive liposome that would selectively degrade under locally acidic vaginal conditions. The novel pH-sensitive liposome was engineered to form a thermogel at body temperature and to degrade in an acidic environment.Results: A dual-sensitive liposome gel with a high encapsulation efficiency of arctigenin was formed and improved the solubility of arctigenin characterized by Fourier transform infrared spectroscopy and differential scanning calorimetry. The dual-sensitive liposome gel with a sol-gel transition at body temperature was degraded in a pH-dependent manner, and was stable for a long period of time at neutral and basic pH, but cleavable under acidic conditions (pH 5.0. Arctigenin encapsulated in a dual-sensitive liposome gel was more stable and less toxic than arctigenin loaded into pH-sensitive liposomes. In vitro drug release results indicated that dual-sensitive liposome gels showed constant release of arctigenin over 3 days, but showed sustained release of arctigenin in buffers at pH 7.4 and pH 9.0.Conclusion: This research has shed some light on a pH and temperature dual-sensitive liposome gel using a cleavable mPEG-Hz-CHEMS polymer for vaginal delivery.Keywords: mPEG-Hz-CHEMS polymer, pH-sensitive liposomes, thermosensitive

Model experiments on the sensitization of polyethylene cross-linking of oligobutadienes

International Nuclear Information System (INIS)

Brede, O.; Beckert, D.; Hoesselbarth, B.; Specht, W.; Tannert, F.; Wunsch, K.

1988-01-01

In presence of ≥ 1 % of 1,2-oligobutadiene the efficiency of the radiation-induced cross-linking of polyethylene was found to be increased in comparison to the pure matrix. Model experiments with solutions of the sensitizer in long chain n-alkanes showed that after addition of alkyl radicals onto the oligobutadiene (reaction with the vinyl groups) the sensitizer forms an own network which is grafted by the alkyl groups. In comparison to this grafting reaction proceeding with G of about 5 the vinyl consumption happened with about the threefold of it indicating a short (intra- and intermolecular) vinyl reaction chain. Pulse radiolysis measurements in solutions of the 1,2-oligobutadiene in n-hexadecane and in molten PE blends resulted in the observation of radical transients of the cross-linking reaction. (author)

Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

International Nuclear Information System (INIS)

Utsumi, H.; Elkind, M.M.

1983-01-01

A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of these cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal

New 1,3,4-Oxadiazole Based Photosensitizers for Dye Sensitized Solar Cells (DSSCs

Directory of Open Access Journals (Sweden)

Umer Mehmood

2015-01-01

Full Text Available 1,3,4-Oxadiazole based photosensitizers with biphenyl, naphthalene, anthracene, and triphenylamine as the electron-donating moiety were synthesized for solar cell applications. In these photosensitizers, cyano groups were introduced as the electron acceptor and the anchor group because of their high electron-withdrawing ability and strong bonding to the semiconductor. Oxadiazole isomers were used as the π-conjugation system, which bridges the donor-acceptor systems. The electrochemical and optical properties of the sensitizers were investigated both in their native form and upon incorporation into dye sensitized solar cells. The results of UV-visible absorption spectroscopy, electrochemical impedance spectroscopic measurements, and photocurrent voltage characteristics indicate that 1,3,4-oxadiazole pi-spacer with the anthracene moiety has the highest efficiency of 2.58%. Density functional theory was employed to optimize the structures of the sensitizers and the TiO2 cluster.

Thymidine kinase deficient human cells have increased UV sensitivity in their capacity to support herpes simplex virus but normal UV sensitivity for colony formation

International Nuclear Information System (INIS)

Rainbow, A.J.

1989-01-01

A thymidine kinase deficient (tk - ) and two thymidine kinase proficient (tk + ) human cell lines were compared for UV sensitivity using colony-forming ability as well as their capacity to support the plaque formation of herpes simplex type 1 (HSV-1).The tk - line (143 cells) was a derivative of one of the tk + lines (R970-5), whereas the other tk + line (AC4 cells) was a derivative of the 143 cells obtained by transfection with purified sheared HSV-2 DNA encoding the viral tk gene. 143, R970-5 and AC4 cells showed a similar UV sensitivity for colony-forming ability. In contrast, the capacity to support HSV-1 plaque formation immediately (within 1 h) afte UV-irradiation was reduced to a greater extent in the 143 cells compared to the R970-5 and AC4 cells. Capacity curves for plaque formation of the HSV-1: KOS wild-type (tk + ) strain were similar to those for the HSV-1: PTK3B mutant (tk - ) strain were similar to those for the HSV-1: PTK3B mutant (tk - ) strain in the 3 cell strains, indicating that the viral tk gene does not influence the ability of HSV-1 to form plaques in UV-irradiated compared to unirradiated human cells. Cellular capacity for HSV-1 plaque formation was found to recover in both tk - and tk + cells for cultures infected 24 h after UV-irradiation. These results suggest that repair of UV-damaged DNA takes place to a similar extent in both tk - and tk + human cells, but the kinetics of repair are initially slower in tk - compared to tk + human cells. (author). 33 refs.; 3 figs.; 1 tab

Developing cultural sensitivity

DEFF Research Database (Denmark)

Ruddock, Heidi; Turner, deSalle

2007-01-01

. Background. Many countries are becoming culturally diverse, but healthcare systems and nursing education often remain mono-cultural and focused on the norms and needs of the majority culture. To meet the needs of all members of multicultural societies, nurses need to develop cultural sensitivity......Title. Developing cultural sensitivity: nursing students’ experiences of a study abroad programme Aim. This paper is a report of a study to explore whether having an international learning experience as part of a nursing education programme promoted cultural sensitivity in nursing students...... and incorporate this into caregiving. Method. A Gadamerian hermeneutic phenomenological approach was adopted. Data were collected in 2004 by using in-depth conversational interviews and analysed using the Turner method. Findings. Developing cultural sensitivity involves a complex interplay between becoming...

Heteromeric Slick/Slack K+ channels show graded sensitivity to cell volume changes.

Science.gov (United States)

Tejada, Maria A; Hashem, Nadia; Calloe, Kirstine; Klaerke, Dan A

2017-01-01

Slick and Slack high-conductance K+ channels are found in the CNS, kidneys, pancreas, among other organs, where they play an important role in cell excitability as well as in ion transport processes. They are both activated by Na+ and Cl- but show a differential regulation by cell volume changes. Slick has been shown to be regulated by cell volume changes, whereas Slack is insensitive. α-subunits of these channels form homomeric as well as heteromeric channels. It is the aim of this work to explore whether the subunit composition of the Slick/Slack heteromeric channel affects the response to osmotic challenges. In order to provide with the adequate water permeability to the cell membrane of Xenopus laevis oocytes, mRNA of aquaporin 1 was co-expressed with homomeric or heteromeric Slick and Slack α-subunits. Oocytes were superfused with hypotonic or hypertonic buffers and changes in currents were measured by two-electrode voltage clamp. This work presents the first heteromeric K+ channel with a characteristic graded sensitivity to small and fast changes in cell volume. Our results show that the cell volume sensitivity of Slick/Slack heteromeric channels is dependent on the number of volume sensitive Slick α-subunits in the tetrameric channels, giving rise to graded cell volume sensitivity. Regulation of the subunit composition of a channel may constitute a novel mechanism to determine volume sensitivity of cells.

Uncertainty and sensitivity assessments of GPS and GIS integrated applications for transportation.

Science.gov (United States)

Hong, Sungchul; Vonderohe, Alan P

2014-02-10

Uncertainty and sensitivity analysis methods are introduced, concerning the quality of spatial data as well as that of output information from Global Positioning System (GPS) and Geographic Information System (GIS) integrated applications for transportation. In the methods, an error model and an error propagation method form a basis for formulating characterization and propagation of uncertainties. They are developed in two distinct approaches: analytical and simulation. Thus, an initial evaluation is performed to compare and examine uncertainty estimations from the analytical and simulation approaches. The evaluation results show that estimated ranges of output information from the analytical and simulation approaches are compatible, but the simulation approach rather than the analytical approach is preferred for uncertainty and sensitivity analyses, due to its flexibility and capability to realize positional errors in both input data. Therefore, in a case study, uncertainty and sensitivity analyses based upon the simulation approach is conducted on a winter maintenance application. The sensitivity analysis is used to determine optimum input data qualities, and the uncertainty analysis is then applied to estimate overall qualities of output information from the application. The analysis results show that output information from the non-distance-based computation model is not sensitive to positional uncertainties in input data. However, for the distance-based computational model, output information has a different magnitude of uncertainties, depending on position uncertainties in input data.

Quantitative determination of solid-state forms of a pharmaceutical development compound in drug substance and tablets.

Science.gov (United States)

Xie, Yong; Tao, Wenle; Morrison, Henry; Chiu, Rick; Jona, Janan; Fang, Jan; Cauchon, Nina

2008-10-01

Common analytical techniques including Raman, NIR, and XRD were evaluated for quantitative determination of three solid-state forms (amorphous, Form B and Form C) of a development compound. Raman spectroscopy was selected as the primary analytical technique with sufficient sensitivity to monitor and quantify the neat drug substance alone and in the drug product. A reliable multivariate curve resolution (MCR) method based on the second derivative Raman measurements of the three pure physical forms was developed and validated with 3.5% root mean square error of prediction (RMSEP) for Form B, which was selected as the preferred form for further development. A partial least squares (PLS) algorithm was also used for the multivariate calibration of both the NIR and Raman measurements. The long-term stability of Form B as a neat active pharmaceutical ingredient (API) and in a tablet formulation was quantitatively monitored under various stress conditions of temperature and moisture. Moisture, temperature, excipients and compression were found to have significant effects on the phase transition behavior of Form B.

Lithologic Control on the Form of Soil Mantled Hillslopes

Science.gov (United States)

Johnstone, S. A.; Hilley, G. E.

2014-12-01

Slopes on steady-state soil-mantled hillslopes tend to increase downslope in a way that balances local transport capacity with the sediment supplied from progressively larger source areas. Most predictions for the transport of soil depend purely on topographic slope and constants. Thus, soil mantled topography should evolve toward smooth forms in which soils act to buffer these forms from the underlying geologic structure. However, in the Gabilan Mesa, CA, oscillations in the slope of soil-mantled hillslopes mirror oscillations in the underlying stratigraphy. Using field measurements of stratigraphy and soil depths, topographic analysis, and numerical modeling, we demonstrate that variations in rock type can impact the form of soil-mantled hillslopes. Specifically, variations in the properties of underlying rocks may yield different soil thicknesses. Balancing transport rates across these variations in thickness requires slopes to change when soil transport depends on both soil thickness and slope. A compilation of published data on the variation in activity with depth of various transport processes provides the basis for a geomorphic transport law (GTL) that generalizes the depth dependence of various transport processes. While this GTL is explicitly depth dependent, it is also capable of describing situations in which hillslope transport is relatively insensitive to variations in thickness and therefore essentially equivalent to existing formulations. We use dimensional analysis and numerical modeling to demonstrate the conditions under which transport on soil mantled slopes, and consequently topographic forms, may be sensitive to variations in soil thickness and therefore lithology.

75 FR 51093 - Agency Information Collection Activities: Form I-864, Form I-864A, Form I-864EZ, and Form I-864W...

Science.gov (United States)

2010-08-18

... DEPARTMENT OF HOMELAND SECURITY U.S. Citizenship and Immigration Services Agency Information... of Homeland Security, U.S. Citizenship and Immigration Services (USCIS) will be submitting the...: Form I-864, Form I-864A, Form I-864EZ, and Form I-864W; U.S. Citizenship and Immigration Services...

The relationship between the anoxic sensitivity and the extent of sensitization by nitrous oxide

Energy Technology Data Exchange (ETDEWEB)

Ewing, D.; Walton, H.L.; Guilfoil, D.S.; Ohm, M.B. (Hahnemann Univ., Philadelphia, PA (USA). Dept. of Radiation Oncology and Nuclear Medicine)

1991-03-01

Nitrous oxide reacts during irradiation to increase the yield of center dotOH, a radical many believe to be a major cause of lethality. Logically, one would expect N{sub 2}O to be a radiation sensitizer. In some instances it is, while in others it is not. In some cases we can explain why N{sub 2}O fails to sensitize; factors such as dose rate, cell concentration, buffer composition and ionic strength all influence when N{sub 2}O will sensitize and if it sensitizes, by what magnitude. Based on the results presented here with multiple strains of procaryotic and eucaryotic cells, we believe the anoxic sensitivity is another critical factor that governs whether N{sub 2}O will sensitize. Our data, with data from the literature, show a relationship between the anoxic sensitivity and the N{sub 2}O enhancement ratio. N{sub 2}O does not sensitize in vitro unless the anoxic sensitivity (inactivation constant, K) is less than {similar to} 0.2 daGy{sup -1}. (author).

Semi-solid metal forming of beryllium-reinforced aluminum alloys

International Nuclear Information System (INIS)

Haws, W.; Lane, L.; Marder, J.; Nicholas, N.

1995-01-01

A Powder Metallurgy (PM) based, Semi-Solid Metal (SSM) forming process has been developed to produce low cost near-net shapes of beryllium-reinforced aluminum alloys. Beryllium acts as a reinforcing additive to the aluminum, in which there is nearly no mutual solid solubility. The modulus of elasticity of the alloy dramatically increases, while the density and thermal expansion coefficient decrease with increasing beryllium content. The material is suitable for complex thermal management and vibration resistance applications, as well as for airborne components which are density and stiffness sensitive. The forming process involves heating a blank of the material to a temperature at which the aluminum is semi-solid and the beryllium is solid. The semi-solid blank is then injected without turbulence into a permanent mold. High quality, near net shape components can be produced which are functionally superior to those produced by other permanent mold processes. Dimensional accuracy is equivalent to or better than that obtained in high pressure die casting. Cost effectiveness is the primary advantage of this technique compared to other forming processes. The advantages and limitations of the process are described. Physical and mechanical property data are presented, as well as directions for future investigation

A TOUCH-SENSITIVE DEVICE

DEFF Research Database (Denmark)

2009-01-01

The present invention relates to an optical touch-sensitive device and a method of determining a position and determining a position change of an object contacting an optical touch sensitive device. In particular, the present invention relates to an optical touch pad and a method of determining...... a position and determining a position change of an object contacting an optical touch pad. A touch-sensitive device, according to the present invention may comprise a light source, a touch- sensitive waveguide, a detector array, and a first light redirecting member, wherein at least a part of the light...... propagating towards a specific point of the detector array is prevented from being incident upon the specific point of the detector array when an object contacts a touch-sensitive surface of the touch-sensitive waveguide at a corresponding specific contact point....

Towards an exact theory of linear absorbance and circular dichroism of pigment-protein complexes: Importance of non-secular contributions

International Nuclear Information System (INIS)

Dinh, Thanh-Chung; Renger, Thomas

2015-01-01

A challenge for the theory of optical spectra of pigment-protein complexes is the equal strength of the pigment-pigment and the pigment-protein couplings. Treating both on an equal footing so far can only be managed by numerically costly approaches. Here, we exploit recent results on a normal mode analysis derived spectral density that revealed the dominance of the diagonal matrix elements of the exciton-vibrational coupling in the exciton state representation. We use a cumulant expansion technique that treats the diagonal parts exactly, includes an infinite summation of the off-diagonal parts in secular and Markov approximations, and provides a systematic perturbative way to include non-secular and non-Markov corrections. The theory is applied to a model dimer and to chlorophyll (Chl) a and Chl b homodimers of the reconstituted water-soluble chlorophyll-binding protein (WSCP) from cauliflower. The model calculations reveal that the non-secular/non-Markov effects redistribute oscillator strength from the strong to the weak exciton transition in absorbance and they diminish the rotational strength of the exciton transitions in circular dichroism. The magnitude of these corrections is in a few percent range of the overall signal, providing a quantitative explanation of the success of time-local convolution-less density matrix theory applied earlier. A close examination of the optical spectra of Chl a and Chl b homodimers in WSCP suggests that the opening angle between Q y transition dipole moments in Chl b homodimers is larger by about 9 ∘ than for Chl a homodimers for which a crystal structure of a related WSCP complex exists. It remains to be investigated whether this change is due to a different mutual geometry of the pigments or due to the different electronic structures of Chl a and Chl b

Towards an exact theory of linear absorbance and circular dichroism of pigment-protein complexes: Importance of non-secular contributions

Energy Technology Data Exchange (ETDEWEB)

Dinh, Thanh-Chung; Renger, Thomas, E-mail: thomas.renger@jku.at [Institut für Theoretische Physik, Johannes Kepler University Linz, Altenberger Str. 69, 4040 Linz (Austria)

2015-01-21

A challenge for the theory of optical spectra of pigment-protein complexes is the equal strength of the pigment-pigment and the pigment-protein couplings. Treating both on an equal footing so far can only be managed by numerically costly approaches. Here, we exploit recent results on a normal mode analysis derived spectral density that revealed the dominance of the diagonal matrix elements of the exciton-vibrational coupling in the exciton state representation. We use a cumulant expansion technique that treats the diagonal parts exactly, includes an infinite summation of the off-diagonal parts in secular and Markov approximations, and provides a systematic perturbative way to include non-secular and non-Markov corrections. The theory is applied to a model dimer and to chlorophyll (Chl) a and Chl b homodimers of the reconstituted water-soluble chlorophyll-binding protein (WSCP) from cauliflower. The model calculations reveal that the non-secular/non-Markov effects redistribute oscillator strength from the strong to the weak exciton transition in absorbance and they diminish the rotational strength of the exciton transitions in circular dichroism. The magnitude of these corrections is in a few percent range of the overall signal, providing a quantitative explanation of the success of time-local convolution-less density matrix theory applied earlier. A close examination of the optical spectra of Chl a and Chl b homodimers in WSCP suggests that the opening angle between Q{sub y} transition dipole moments in Chl b homodimers is larger by about 9{sup ∘} than for Chl a homodimers for which a crystal structure of a related WSCP complex exists. It remains to be investigated whether this change is due to a different mutual geometry of the pigments or due to the different electronic structures of Chl a and Chl b.

Theory of Inclusive Scattering of Polarized Electrons by Polarized $^{3}$He and the Neutron Form Factors

OpenAIRE

Atti, C. Ciofi degli; Pace, E.; Salmé, G.

1993-01-01

The theory of inclusive lepton scattering of polarized leptons by polarized J = 1/2 hadrons is presented and the origin of different expressions for the polarized nuclear response function appearing in the literature is explained. The sensitivity of the longitudinal asymmetry upon the neutron form factors is investigated.

First evidence that drugs of abuse produce behavioral sensitization and cross-sensitization in planarians

Science.gov (United States)

Rawls, Scott M.; Patil, Tavni; Yuvasheva, Ekaternia; Raffa, Robert B.

2010-01-01

Behavioral sensitization in mammals, including humans, is sensitive to factors such as administration route, testing environment, and pharmacokinetic confounds, unrelated to the drugs themselves, that are difficult to eliminate. Simpler animals less susceptible to these confounding influences may be advantageous substitutes for studying sensitization. We tested this hypothesis by determining if planarians display sensitization and cross-sensitization to cocaine and glutamate. Planarian hyperactivity was quantified as the number of C-like hyperkinesias during a 1-min drug exposure. Planarians exposed initially to cocaine (or glutamate) on day 1 were challenged with cocaine (or glutamate) after 2 or 6 days of abstinence. Acute cocaine or glutamate produced concentration-related hyperactivity. Cocaine or glutamate challenge after 2 and 6 days of abstinence enhanced the hyperactivity, indicating the substances produced planarian behavioral sensitization (pBS). Cross-sensitization experiments showed that cocaine produced greater hyperactivity in planarians previously exposed to glutamate than in glutamate-naïve planarians, and vice versa. Behavioral responses were pharmacologically selective because neither scopolamine nor caffeine produced pBS despite causing hyperactivity after initial administration, and acute GABA did not cause hyperactivity. Demonstration of pharmacologically-selective behavioral sensitization in planarians suggests these flatworms represent a sensitive in vivo model to study cocaine behavioral sensitization and to screen potential abuse-deterrent therapeutics. PMID:20512030

Mechanisms involved in the chemical inhibition of the Eosin-sensitized photooxidation of trypsin

Energy Technology Data Exchange (ETDEWEB)

Rizzuto, F.; Spikes, J.D.

1975-01-01

A large series of compounds was screened for ability to protect trypsin from eosin-sensitized photodynamic inactivation. Eosin-sensitized photooxidation reactions of this type typically proceed via the triplet state of the dye and often involve singlet state oxygen as the oxidizing entity. In order to determine the mechanisms by which trypsin is protected from photoinactivation, a number of good protective agents (inhibitors) and some non-protective agents were selected for more detailed flash photolysis studies. Good inhibitors such as p-phenylenediamine, n-propyl gallate, serotonin creatinine sulfate and p-toluenediamine competed efficiently with oxygen and with trypsin for reaction with the triplet state of eosin. The inhibitors were shown to quench triplet eosin to the ground state and/or reduce triplet eosin to form the semireduced eosin radical and an oxidized form of the inhibitor. In the latter case, oxidized inhibitor could react by a reverse electron transfer reaction with the semireduced eosin radical to regenerate ground state eosin and the inhibitor. The good inhibitors also competed effectively with trypsin for oxidation by semioxidized eosin, thus giving another possible protective mechanism. Non-inhibitors such as halogen ions and the paramagnetic ions Co/sup + +/, Cu/sup + +/ and Mn/sup + +/ reacted only slowly with triplet and with semioxidized eosin. The primary pathway for the eosin-sensitized photooxidation of trypsin at pH 8.0 involved singlet oxygen, although semioxidized eosin may also participate.

Advances in metal forming expert system for metal forming

CERN Document Server

Hingole, Rahulkumar Shivajirao

2015-01-01

This comprehensive book offers a clear account of the theory and applications of advanced metal forming. It provides a detailed discussion of specific forming processes, such as deep drawing, rolling, bending extrusion and stamping. The author highlights recent developments of metal forming technologies and explains sound, new and powerful expert system techniques for solving advanced engineering problems in metal forming. In addition, the basics of expert systems, their importance and applications to metal forming processes, computer-aided analysis of metalworking processes, formability analysis, mathematical modeling and case studies of individual processes are presented.

Rash impulsiveness and reward sensitivity in relation to risky drinking by university students: potential roles of frontal systems.

Science.gov (United States)

Lyvers, Michael; Duff, Helen; Basch, Vanessa; Edwards, Mark S

2012-08-01

Two forms of impulsivity, rash impulsiveness and reward sensitivity, have been proposed to reflect aspects of frontal lobe functioning and promote substance use. The present study examined these two forms of impulsivity as well as frontal lobe symptoms in relation to risky drinking by university students. University undergraduates aged 18-26years completed the Alcohol Use Disorders Identification Test (AUDIT), Barratt Impulsiveness Scale (BIS-11), Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ), Frontal Systems Behavior Scale (FrSBe), and a demographics questionnaire assessing age, gender, and age of onset of weekly drinking (AOD). AUDIT-defined harmful drinkers reported earlier AOD and scored higher on BIS-11, the Sensitivity to Reward (SR) scale of the SPSRQ, and the Disinhibition and Executive Dysfunction scales of the FrSBe compared to lower risk groups. Differences remained significant after controlling for duration of alcohol exposure. Path analyses indicated that the influence of SR on AUDIT was mediated by FrSBe Disinhibition, whereas the influence of BIS-11 on AUDIT was mediated by both Disinhibition and Executive Dysfunction scales of the FrSBe. Findings tentatively suggest that the influence of rash impulsiveness on drinking may reflect dysfunction in dorsolateral prefrontal and orbitofrontal systems, whereas the influence of reward sensitivity on drinking may primarily reflect orbitofrontal dysfunction. Irrespective of the underlying functional brain systems involved, results appear to be more consistent with a pre-drinking trait interpretation than effects of alcohol exposure. Copyright © 2012 Elsevier Ltd. All rights reserved.

The molecular mechanism underlying anthocyanin metabolism in apple using the MdMYB16 and MdbHLH33 genes.

Science.gov (United States)

Xu, Haifeng; Wang, Nan; Liu, Jingxuan; Qu, Changzhi; Wang, Yicheng; Jiang, Shenghui; Lu, Ninglin; Wang, Deyun; Zhang, Zongying; Chen, Xuesen

2017-05-01

MdMYB16 forms homodimers and directly inhibits anthocyanin synthesis via its C-terminal EAR repressor. It weakened the inhibitory effect of MdMYB16 on anthocyanin synthesis when overexpressing MdbHLH33 in callus overexpressing MdMYB16. MdMYB16 could interact with MdbHLH33. Anthocyanins are strong antioxidants that play a key role in the prevention of cardiovascular disease, cancer, and diabetes. The germplasm of Malus sieversii f. neidzwetzkyana is important for the study of anthocyanin metabolism. To date, only limited studies have examined the negative regulatory mechanisms underlying anthocyanin synthesis in apple. Here, we analyzed the relationship between anthocyanin levels and MdMYB16 expression in mature Red Crisp 1-5 apple (M. domestica) fruit, generated an evolutionary tree, and identified an EAR suppression sequence and a bHLH binding motif of the MdMYB16 protein using protein sequence analyses. Overexpression of MdMYB16 or MdMYB16 without bHLH binding sequence (LBSMdMYB16) in red-fleshed callus inhibited MdUFGT and MdANS expression and anthocyanin synthesis. However, overexpression of MdMYB16 without the EAR sequence (LESMdMYB16) in red-fleshed callus had no inhibitory effect on anthocyanin. The yeast one-hybrid assay showed that MdMYB16 and LESMdMYB16 interacted the promoters of MdANS and MdUFGT, respectively. Yeast two-hybrid, pull-down, and bimolecular fluorescence complementation assays showed that MdMYB16 formed homodimers and interacted with MdbHLH33, however, the LBSMdMYB16 could not interact with MdbHLH33. We overexpressed MdbHLH33 in callus overexpressing MdMYB16 and found that it weakened the inhibitory effect of MdMYB16 on anthocyanin synthesis. Together, these results suggested that MdMYB16 and MdbHLH33 may be important part of the regulatory network controlling the anthocyanin biosynthetic pathway.

Salience in Second Language Acquisition:Physical form, learner attention, and instructional focus

Directory of Open Access Journals (Sweden)

Myrna C Cintrón-Valentín

2016-08-01

Full Text Available We consider the role of physical form, prior experience, and form focused instruction (FFI in adult language learning. (1 When presented with competing cues to interpretation, learners are more likely to attend to physically more salient cues in the input. (2 Learned attention is an associative learning phenomenon where prior-learned cues block those that are experienced later. (3 The low salience of morphosyntactic cues can be overcome by FFI, which leads learners to attend cues which might otherwise be ignored. Experiment 1 used eye-tracking to investigate how language background influences learners’ attention to morphological cues, as well as the attentional processes whereby different types of FFI overcome low cue salience, learned attention and blocking. Chinese native speakers (no L1 verb-tense morphology viewed Latin utterances combining lexical and morphological cues to temporality under control conditions (CC and three types of explicit FFI: grammar instruction (VG, verb salience with textual enhancement (VS, and verb pretraining (VP, and their use of these cues was assessed in a comprehension test. CC participants were significantly more sensitive to the adverbs than verb morphology. Instructed participants showed greater sensitivity to the verbs. These results reveal attentional processes whereby learners’ prior linguistic experience can shape their attention toward cues in the input, and whereby FFI helps learners overcome the long-term blocking of verb-tense morphology. Experiment 2 examined the role of modality of input presentation – aural or visual – in L1 English learners’ attentional focus on morphological cues and the effectiveness of different FFI manipulations. CC participants showed greater sensitivity toward the adverb cue. FFI was effective in increasing attention to verb-tense morphology, however, the processing of morphological cues was considerably more difficult under aural presentation. From visual exposure

Finnish Teachers’ Ethical Sensitivity

Directory of Open Access Journals (Sweden)

Elina Kuusisto

2012-01-01

Full Text Available The study examined the ethical sensitivity of Finnish teachers (=864 using a 28-item Ethical Sensitivity Scale Questionnaire (ESSQ. The psychometric qualities of this instrument were analyzed, as were the differences in self-reported ethical sensitivity between practicing and student teachers and teachers of different subjects. The results showed that the psychometric qualities of the ESSQ were satisfactory and enabled the use of an explorative factor analysis. All Finnish teachers rated their level of ethical sensitivity as high, which indicates that they had internalized the ethical professionalism of teaching. However, practicing teachers’ assessments were higher than student teachers’. Moreover, science as a subject was associated with lower self-ratings of ethical sensitivity.

Sensitizing pigment in the fly

International Nuclear Information System (INIS)

Vogt, K.; Kirschfeld, K.

1983-01-01

The sensitizing pigment hypothesis for the high UV sensitivity in fly photoreceptors (R1-6) is further substantiated by measurements of the polarisation sensitivity in the UV. The quantum yield of the energy transfer from sensitizing pigment to rhodopsin was estimated by electrophysiological measurements of the UV sensitivity and the rhabdomeric absorptance (at 490 nm) in individual receptor cells. The transfer efficiency is >=0.75 in receptors with an absorptance in the rhabdomeres of 0.55-0.95. This result suggests that the sensitizing pigment is bound in some way to the rhodopsin. A ratio of two molecules of sensitizing pigment per one rhodopsin is proposed. (orig.)

Kinematic sensitivity of robot manipulators

Science.gov (United States)

Vuskovic, Marko I.

1989-01-01

Kinematic sensitivity vectors and matrices for open-loop, n degrees-of-freedom manipulators are derived. First-order sensitivity vectors are defined as partial derivatives of the manipulator's position and orientation with respect to its geometrical parameters. The four-parameter kinematic model is considered, as well as the five-parameter model in case of nominally parallel joint axes. Sensitivity vectors are expressed in terms of coordinate axes of manipulator frames. Second-order sensitivity vectors, the partial derivatives of first-order sensitivity vectors, are also considered. It is shown that second-order sensitivity vectors can be expressed as vector products of the first-order sensitivity vectors.

Computing derivative-based global sensitivity measures using polynomial chaos expansions

International Nuclear Information System (INIS)

Sudret, B.; Mai, C.V.

2015-01-01

In the field of computer experiments sensitivity analysis aims at quantifying the relative importance of each input parameter (or combinations thereof) of a computational model with respect to the model output uncertainty. Variance decomposition methods leading to the well-known Sobol' indices are recognized as accurate techniques, at a rather high computational cost though. The use of polynomial chaos expansions (PCE) to compute Sobol' indices has allowed to alleviate the computational burden though. However, when dealing with large dimensional input vectors, it is good practice to first use screening methods in order to discard unimportant variables. The derivative-based global sensitivity measures (DGSMs) have been developed recently in this respect. In this paper we show how polynomial chaos expansions may be used to compute analytically DGSMs as a mere post-processing. This requires the analytical derivation of derivatives of the orthonormal polynomials which enter PC expansions. Closed-form expressions for Hermite, Legendre and Laguerre polynomial expansions are given. The efficiency of the approach is illustrated on two well-known benchmark problems in sensitivity analysis. - Highlights: • Derivative-based global sensitivity measures (DGSM) have been developed for screening purpose. • Polynomial chaos expansions (PC) are used as a surrogate model of the original computational model. • From a PC expansion the DGSM can be computed analytically. • The paper provides the derivatives of Hermite, Legendre and Laguerre polynomials for this purpose

Influence of styryl dyes on blood erythrocytes

Science.gov (United States)

Nizomov, Negmat; Barakaeva, Mubaro; Kurtaliev, Eldar N.; Rahimov, Sherzod I.; Khakimova, Dilorom P.; Khodjayev, Gayrat; Yashchuk, Valeriy N.

2008-08-01

It was studied the influence of F, Sbt, Sil, Sbo monomer and homodimer Dst-5, Dst-10, Dbt-5, Dbt-10, Dil-10, Dbo-10 styryl dyes on blood erythrocytes of white rats. It was shown that the homodimer styryl dyes Dst-5, Dbt-5 and Dbo-10 decrease the erythrocytes quantity by 1.5-2 times more as compared with monomer dyes Sbt and Sbo. The main cause of dyes different action is the different oxidation degree of intracellular hemoglobin evoked by these dyes. It was established that the observed effects was connected with different penetration of these dyes through membrane of erythrocytes and with interaction of these dyes with albumin localized in membranes of cells.

[Asymptomatic bacteruiria frequency in pregnant women and uropathogen in vitro antimicrobial sensitivity].

Science.gov (United States)

Hernández Blas, Fernanda; López Carmona, Juan Manuel; Rodríguez Moctezuma, José Raymundo; Peralta Pedrero, María Luisa; Rodríguez Gutiérrez, Román Salvador; Ortiz Aguirre, Alma Rosa

2007-06-01

To estimate the frequency of asymptomatic bacteriuria in pregnant women attended in Family Medicine Units of the Instituto Mexicano del Seguro Social and to determine the in vitro sensitivity rate of the microorganisms to ampicillin, trimethoprim-sulfamethoxazole, nitrofurantoin and amikacin. We carried out an observational, prospective and transversal study at Family Medicine Units 62 and 64 of the Mexico State Delegation, located in the urban area of Mexico City. Women with lesser than 32 weeks of pregnancy without urinary tract symptoms were included. Urine culture of a midstream urine specimen with > or = 10(5) colony forming units/mL urine of an only germen was used as the gold standard. The in vitro antimicrobial sensitivity was established according to the Bauer Kirby technique. 874 pregnant women were included and 73 had a positive urine culture, with a frequency of 8.4%, IC 95% = 6.6 - 10.2%, of asymptomatic bacteriuria. Escherichia coil was the most frequent isolated agent (77%). In vitro sensitivity to ampicillin of the microorganisms isolated was of 27%, IC 95% = 16 - 38%; to trimethoprim-sulfamethoxazole of 40%, IC95% = 29 - 51%; to amikacin of 68%, IC 95% = 57 - 79%, and to nitrofurantoin of 79%, IC 95% = 70 - 88%. The frequency of asymptomatic bacteriuria in the studied population is similar to the reported by the literature. The in vitro sensitivity rates of E. coil to ampicillin and to trimethoprim-sulfamethoxazole are very low. The best sensitivity corresponded to the nitrofurantoin. The treatment of the asymptomatic bacteriuria must be based on the local patterns of antimicrobial sensitivity and resistance.

Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

International Nuclear Information System (INIS)

Huang, Shang-Lang; Chao, Chuck C.-K.

2015-01-01

A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug

Silencing of Taxol-Sensitizer Genes in Cancer Cells: Lack of Sensitization Effects

Energy Technology Data Exchange (ETDEWEB)

Huang, Shang-Lang [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Chao, Chuck C.-K., E-mail: cckchao@mail.cgu.edu.tw [Department of Biochemistry and Molecular Biology, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan (China); Department of Medical Research and Development, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan (China)

2015-06-16

A previous genome-wide screening analysis identified a panel of genes that sensitize the human non-small-cell lung carcinoma cell line NCI-H1155 to taxol. However, whether the identified genes sensitize other cancer cells to taxol has not been examined. Here, we silenced the taxol-sensitizer genes identified (acrbp, atp6v0d2, fgd4, hs6st2, psma6, and tubgcp2) in nine other cancer cell types (including lung, cervical, ovarian, and hepatocellular carcinoma cell lines) that showed reduced cell viability in the presence of a sub-lethal concentration of taxol. Surprisingly, none of the genes studied increased sensitivity to taxol in the tested panel of cell lines. As observed in H1155 cells, SKOV3 cells displayed induction of five of the six genes studied in response to a cell killing dose of taxol. The other cell types were much less responsive to taxol. Notably, four of the five inducible taxol-sensitizer genes tested (acrbp, atp6v0d2, psma6, and tubgcp2) were upregulated in a taxol-resistant ovarian cancer cell line. These results indicate that the previously identified taxol-sensitizer loci are not conserved genetic targets involved in inhibiting cell proliferation in response to taxol. Our findings also suggest that regulation of taxol-sensitizer genes by taxol may be critical for acquired cell resistance to the drug.

Sensitivity and uncertainty analysis

CERN Document Server

Cacuci, Dan G; Navon, Ionel Michael

2005-01-01

As computer-assisted modeling and analysis of physical processes have continued to grow and diversify, sensitivity and uncertainty analyses have become indispensable scientific tools. Sensitivity and Uncertainty Analysis. Volume I: Theory focused on the mathematical underpinnings of two important methods for such analyses: the Adjoint Sensitivity Analysis Procedure and the Global Adjoint Sensitivity Analysis Procedure. This volume concentrates on the practical aspects of performing these analyses for large-scale systems. The applications addressed include two-phase flow problems, a radiative c

Sound-by-sound thalamic stimulation modulates midbrain auditory excitability and relative binaural sensitivity in frogs.

Science.gov (United States)

Ponnath, Abhilash; Farris, Hamilton E

2014-01-01

Descending circuitry can modulate auditory processing, biasing sensitivity to particular stimulus parameters and locations. Using awake in vivo single unit recordings, this study tested whether electrical stimulation of the thalamus modulates auditory excitability and relative binaural sensitivity in neurons of the amphibian midbrain. In addition, by using electrical stimuli that were either longer than the acoustic stimuli (i.e., seconds) or presented on a sound-by-sound basis (ms), experiments addressed whether the form of modulation depended on the temporal structure of the electrical stimulus. Following long duration electrical stimulation (3-10 s of 20 Hz square pulses), excitability (spikes/acoustic stimulus) to free-field noise stimuli decreased by 32%, but returned over 600 s. In contrast, sound-by-sound electrical stimulation using a single 2 ms duration electrical pulse 25 ms before each noise stimulus caused faster and varied forms of modulation: modulation lasted sound-by-sound electrical stimulation varied between different acoustic stimuli, including for different male calls, suggesting modulation is specific to certain stimulus attributes. For binaural units, modulation depended on the ear of input, as sound-by-sound electrical stimulation preceding dichotic acoustic stimulation caused asymmetric modulatory effects: sensitivity shifted for sounds at only one ear, or by different relative amounts for both ears. This caused a change in the relative difference in binaural sensitivity. Thus, sound-by-sound electrical stimulation revealed fast and ear-specific (i.e., lateralized) auditory modulation that is potentially suited to shifts in auditory attention during sound segregation in the auditory scene.

Quantitative assay for the number of leukemic spleen colony forming unit in radiation-induced murine myeloid leukemia

Energy Technology Data Exchange (ETDEWEB)

Nara, N [Tokyo Medical and Dental Univ. (Japan). School of Medicine; Bessho, M

1981-11-01

In mice with myelogenous leukemia, leukemic spleen colony forming units were assayed quantitatively. When 5 x 10/sup 3/ - 2 x 10/sup 4/ leukemic cells were transplanted to other mice of the same strain, a rectilinear relationship (p < 0.01) was found between the number of the cells transplanted and that of the colonies formed on the surface of the spleen. From these results, the authors considered that myelogenous leukemia in mice is an adequate model for acute myelogenous leukemia in human adults, and that the quantitative assay of the leukemic colony forming units can be used for sensitivity tests of antileukemic agents.

Impact of the putative cancer stem cell markers and growth factor receptor expression on the sensitivity of ovarian cancer cells to treatment with various forms of small molecule tyrosine kinase inhibitors and cytotoxic drugs.

Science.gov (United States)

Puvanenthiran, Soozana; Essapen, Sharadah; Seddon, Alan M; Modjtahedi, Helmout

2016-11-01

Increased expression and activation of human epidermal growth factor receptor (EGFR) and HER-2 have been reported in numerous cancers. The aim of this study was to determine the sensitivity of a large panel of human ovarian cancer cell lines (OCCLs) to treatment with various forms of small molecule tyrosine kinase inhibitors (TKIs) and cytotoxic drugs. The aim was to see if there was any association between the protein expression of various biomarkers including three putative ovarian cancer stem cell (CSC) markers (CD24, CD44, CD117/c-Kit), P-glycoprotein (P-gp), and HER family members and response to treatment with these agents. The sensitivity of 10 ovarian tumour cell lines to the treatment with various forms of HER TKIs (gefitinib, erlotinib, lapatinib, sapitinib, afatinib, canertinib, neratinib), as well as other TKIs (dasatinib, imatinib, NVP-AEW541, crizotinib) and cytotoxic agents (paclitaxel, cisplatin and doxorubicin), as single agents or in combination, was determined by SRB assay. The effect on these agents on the cell cycle distribution, and downstream signaling molecules and tumour migration were determined using flow cytometry, western blotting, and the IncuCyte Clear View cell migration assay respectively. Of the HER inhibitors, the irreversible pan-TKIs (canertinib, neratinib and afatinib) were the most effective TKIs for inhibiting the growth of all ovarian cancer cells, and for blocking the phosphorylation of EGFR, HER-2, AKT and MAPK in SKOV3 cells. Interestingly, while the majority of cancer cells were highly sensitive to treatment with dasatinib, they were relatively resistant to treatment with imatinib (i.e., IC50 >10 µM). Of the cytotoxic agents, paclitaxel was the most effective for inhibiting the growth of OCCLs, and of various combinations of these drugs, only treatment with a combination of NVP-AEW541 and paclitaxel produced a synergistic or additive anti-proliferative effect in all three cell lines examined (i.e., SKOV3, Caov3, ES2

Multiple chemical sensitivity