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Sample records for light chain variable

  1. Formation of amyloid fibers by monomeric light chain variable domains.

    Science.gov (United States)

    Brumshtein, Boris; Esswein, Shannon R; Landau, Meytal; Ryan, Christopher M; Whitelegge, Julian P; Phillips, Martin L; Cascio, Duilio; Sawaya, Michael R; Eisenberg, David S

    2014-10-03

    Systemic light chain amyloidosis is a lethal disease characterized by excess immunoglobulin light chains and light chain fragments composed of variable domains, which aggregate into amyloid fibers. These fibers accumulate and damage organs. Some light chains induce formation of amyloid fibers, whereas others do not, making it unclear what distinguishes amyloid formers from non-formers. One mechanism by which sequence variation may reduce propensity to form amyloid fibers is by shifting the equilibrium toward an amyloid-resistant quaternary structure. Here we identify the monomeric form of the Mcg immunoglobulin light chain variable domain as the quaternary unit required for amyloid fiber assembly. Dimers of Mcg variable domains remain stable and soluble, yet become prone to assemble into amyloid fibers upon disassociation into monomers. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  2. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna

    2011-06-28

    The antigen-binding site of immunoglobulins is formed by six regions, three from the light and three from the heavy chain variable domains, which, on association of the two chains, form the conventional antigen-binding site of the antibody. The mode of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface between the heavy and light chain variable domains and show that there are essentially two different modes for their interaction that can be identified by the presence of key amino acids in specific positions of the antibody sequences. We also show that the different packing modes are related to the type of recognized antigen.

  3. Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

    Science.gov (United States)

    Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

    2018-01-01

    Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

  4. The association of heavy and light chain variable domains in antibodies: implications for antigen specificity.

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Tramontano, Anna

    2011-01-01

    of interaction between the heavy and light chain variable domains affects the relative position of the antigen-binding loops and therefore has an effect on the overall conformation of the binding site. In this article, we analyze the structure of the interface

  5. Mutations in specific structural regions of immunoglobulin light chains are associated with free light chain levels in patients with AL amyloidosis.

    Directory of Open Access Journals (Sweden)

    Tanya L Poshusta

    Full Text Available BACKGROUND: The amyloidoses are protein misfolding diseases characterized by the deposition of amyloid that leads to cell death and tissue degeneration. In immunoglobulin light chain amyloidosis (AL, each patient has a unique monoclonal immunoglobulin light chain (LC that forms amyloid deposits. Somatic mutations in AL LCs make these proteins less thermodynamically stable than their non-amyloidogenic counterparts, leading to misfolding and ultimately the formation of amyloid fibrils. We hypothesize that location rather than number of non-conservative mutations determines the amyloidogenicity of light chains. METHODOLOGY/PRINCIPAL FINDINGS: We performed sequence alignments on the variable domain of 50 kappa and 91 lambda AL light chains and calculated the number of non-conservative mutations over total number of patients for each secondary structure element in order to identify regions that accumulate non-conservative mutations. Among patients with AL, the levels of circulating immunoglobulin free light chain varies greatly, but even patients with very low levels can have very advanced amyloid deposition. CONCLUSIONS: Our results show that in specific secondary structure elements, there are significant differences in the number of non-conservative mutations between normal and AL sequences. AL sequences from patients with different levels of secreted light chain have distinct differences in the location of non-conservative mutations, suggesting that for patients with very low levels of light chains and advanced amyloid deposition, the location of non-conservative mutations rather than the amount of free light chain in circulation may determine the amyloidogenic propensity of light chains.

  6. Fragments of the constant region of immunoglobulin light chains are constituents of AL-amyloid proteins

    DEFF Research Database (Denmark)

    Olsen, K E; Sletten, K; Westermark, Per

    1998-01-01

    Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin l...... light chain are a constituent of the AL-amyloid proteins of kappa type. A specific antiserum has identified these fragments in gel filtration fractions where the absorbance approached the base line after the main retarded peak. The fragments are small and have been overlooked previously......Immunoglobulin light chains are the precursor proteins of AL-amyloidosis. In the fibril formation process properties of the variable part of the immunoglobulin light chains are believed to be of major importance. In this work it is shown that fragments of the constant part of the immunoglobulin...... in the purification process. The significance of the constant part in AL-proteins is unclear, but adds new aspects to the discussion of pre- or post-fibrillogenic cleavage of the immunoglobulin light chains....

  7. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna

    2011-03-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  8. Structural repertoire of immunoglobulin λ light chains

    KAUST Repository

    Chailyan, Anna; Marcatili, Paolo; Cirillo, Davide; Tramontano, Anna

    2011-01-01

    The immunoglobulin λ isotype is present in nearly all vertebrates and plays an important role in the human immune system. Despite its importance, few systematic studies have been performed to analyze the structural conformation of its variable regions, contrary to what is the case for κ and heavy chains. We show here that an analysis of the structures of λ chains allows the definition of a discrete set of recurring conformations (canonical structures) of their hypervariable loops and, most importantly, the identification of sequence constraints that can be used to predict their structure. We also show that the structural repertoire of λ chains is different and more varied than that of the κ chains, consistently with the current view of the involvement of the two major light-chain families in complementary strategies of the immune system to ensure a fine tuning between diversity and stability in antigen recognition. © 2011 Wiley-Liss, Inc.

  9. Assessment of Intrathecal Free Light Chain Synthesis: Comparison of Different Quantitative Methods with the Detection of Oligoclonal Free Light Chains by Isoelectric Focusing and Affinity-Mediated Immunoblotting.

    Science.gov (United States)

    Zeman, David; Kušnierová, Pavlína; Švagera, Zdeněk; Všianský, František; Byrtusová, Monika; Hradílek, Pavel; Kurková, Barbora; Zapletalová, Olga; Bartoš, Vladimír

    2016-01-01

    We aimed to compare various methods for free light chain (fLC) quantitation in cerebrospinal fluid (CSF) and serum and to determine whether quantitative CSF measurements could reliably predict intrathecal fLC synthesis. In addition, we wished to determine the relationship between free kappa and free lambda light chain concentrations in CSF and serum in various disease groups. We analysed 166 paired CSF and serum samples by at least one of the following methods: turbidimetry (Freelite™, SPAPLUS), nephelometry (N Latex FLC™, BN ProSpec), and two different (commercially available and in-house developed) sandwich ELISAs. The results were compared with oligoclonal fLC detected by affinity-mediated immunoblotting after isoelectric focusing. Although the correlations between quantitative methods were good, both proportional and systematic differences were discerned. However, no major differences were observed in the prediction of positive oligoclonal fLC test. Surprisingly, CSF free kappa/free lambda light chain ratios were lower than those in serum in about 75% of samples with negative oligoclonal fLC test. In about a half of patients with multiple sclerosis and clinically isolated syndrome, profoundly increased free kappa/free lambda light chain ratios were found in the CSF. Our results show that using appropriate method-specific cut-offs, different methods of CSF fLC quantitation can be used for the prediction of intrathecal fLC synthesis. The reason for unexpectedly low free kappa/free lambda light chain ratios in normal CSFs remains to be elucidated. Whereas CSF free kappa light chain concentration is increased in most patients with multiple sclerosis and clinically isolated syndrome, CSF free lambda light chain values show large interindividual variability in these patients and should be investigated further for possible immunopathological and prognostic significance.

  10. Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

    International Nuclear Information System (INIS)

    Josephson, Matthew P.; Sikkink, Laura A.; Penheiter, Alan R.; Burghardt, Thomas P.; Ajtai, Katalin

    2011-01-01

    Highlights: ► Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. ► Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. ► It is a widely believed that MYL2 is a poor substrate for smMLCK. ► In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. ► Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca 2+ sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis–Menten V max and K M for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant kinase in cardiac tissue on the basis of its specificity, kinetics, and tissue expression.

  11. Smooth muscle myosin light chain kinase efficiently phosphorylates serine 15 of cardiac myosin regulatory light chain

    Energy Technology Data Exchange (ETDEWEB)

    Josephson, Matthew P.; Sikkink, Laura A. [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Penheiter, Alan R. [Molecular Medicine Program, Mayo Clinic, Rochester, MN 55905 (United States); Burghardt, Thomas P., E-mail: burghardt@mayo.edu [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States); Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN 55905 (United States); Ajtai, Katalin [Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905 (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Cardiac myosin regulatory light chain (MYL2) is phosphorylated at S15. Black-Right-Pointing-Pointer Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase. Black-Right-Pointing-Pointer It is a widely believed that MYL2 is a poor substrate for smMLCK. Black-Right-Pointing-Pointer In fact, smMLCK efficiently and rapidly phosphorylates S15 in MYL2. Black-Right-Pointing-Pointer Phosphorylation kinetics measured by novel fluorescence method without radioactivity. -- Abstract: Specific phosphorylation of the human ventricular cardiac myosin regulatory light chain (MYL2) modifies the protein at S15. This modification affects MYL2 secondary structure and modulates the Ca{sup 2+} sensitivity of contraction in cardiac tissue. Smooth muscle myosin light chain kinase (smMLCK) is a ubiquitous kinase prevalent in uterus and present in other contracting tissues including cardiac muscle. The recombinant 130 kDa (short) smMLCK phosphorylated S15 in MYL2 in vitro. Specific modification of S15 was verified using the direct detection of the phospho group on S15 with mass spectrometry. SmMLCK also specifically phosphorylated myosin regulatory light chain S15 in porcine ventricular myosin and chicken gizzard smooth muscle myosin (S20 in smooth muscle) but failed to phosphorylate the myosin regulatory light chain in rabbit skeletal myosin. Phosphorylation kinetics, measured using a novel fluorescence method eliminating the use of radioactive isotopes, indicates similar Michaelis-Menten V{sub max} and K{sub M} for regulatory light chain S15 phosphorylation rates in MYL2, porcine ventricular myosin, and chicken gizzard myosin. These data demonstrate that smMLCK is a specific and efficient kinase for the in vitro phosphorylation of MYL2, cardiac, and smooth muscle myosin. Whether smMLCK plays a role in cardiac muscle regulation or response to a disease causing stimulus is unclear but it should be considered a potentially significant

  12. Dynein light chain family in Tetrahymena thermophila.

    Science.gov (United States)

    Wilkes, David E; Rajagopalan, Vidyalakshmi; Chan, Clarence W C; Kniazeva, Ekaterina; Wiedeman, Alice E; Asai, David J

    2007-02-01

    Dyneins are large protein complexes that produce directed movement on microtubules. In situ, dyneins comprise combinations of heavy, intermediate, light-intermediate, and light chains. The light chains regulate the locations and activities of dyneins but their functions are not completely understood. We have searched the recently sequenced Tetrahymena thermophila macronuclear genome to describe the entire family of dynein light chains expressed in this organism. We identified fourteen genes encoding putative dynein light chains and seven genes encoding light chain-like proteins. RNA-directed PCR revealed that all 21 genes were expressed. Quantitative real time reverse transcription PCR showed that many of these genes were upregulated after deciliation, indicating that these proteins are present in cilia. Using the nomenclature developed in Chlamydomonas, Tetrahymena expresses two isoforms each of LC2, LC4, LC7, and Tctex1, three isoforms of p28, and six LC8/LC8-like isoforms. Tetrahymena also expresses two LC3-like genes. No Tetrahymena orthologue was found for Chlamydomonas LC5 or LC6. This study provides a complete description of the different genes and isoforms of the dynein light chains that are expressed in Tetrahymena, a model organism in which the targeted manipulation of genes is straightforward. (c) 2006 Wiley-Liss, Inc.

  13. Serum Free Light Chains in Neoplastic Monoclonal Gammopathies: Relative Under-Detection of Lambda Dominant Kappa/Lambda Ratio, and Underproduction of Free Lambda Light Chains, as Compared to Kappa Light Chains, in Patients With Neoplastic Monoclonal Gammopathies.

    Science.gov (United States)

    Lee, Won Sok; Singh, Gurmukh

    2018-07-01

    Quantitative evaluation of serum free light chains is recommended for the work up of monoclonal gammopathies. Immunoglobulin light chains are generally produced in excess of heavy chains. In patients with monoclonal gammopathy, κ/λ ratio is abnormal less frequently with lambda chain lesions. This study was undertaken to ascertain if the levels of overproduction of the two light chain types and their detection rates are different in patients with neoplastic monoclonal gammopathies. Results of serum protein electrophoresis (SPEP), serum protein immunofixation electrophoresis (SIFE), urine protein electrophoresis (UPEP), urine protein immunofixation electrophoresis (UIFE), and serum free light chain assay (SFLCA) in patients with monoclonal gammopathies were examined retrospectively. The κ/λ ratios were appropriately abnormal more often in kappa chain lesions. Ratios of κ/λ were normal in about 25% of patients with lambda chain lesions in whom free homogenous lambda light chains were detectable in urine. An illustrative case suggests underproduction of free lambda light chains, in some instances. The lower prevalence of lambda dominant κ/λ ratio in lesions with lambda light chains is estimated to be due to relative under-detection of lambda dominant κ/λ ratio in about 25% of the patients and because lambda chains are not produced in as much excess of heavy chains as are kappa chains, in about 5% of the patients. The results question the medical necessity and clinical usefulness of the serum free light chain assay. UPEP/UIFE is under-utilized.

  14. Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

    Directory of Open Access Journals (Sweden)

    Helen P McWilliams-Koeppen

    Full Text Available Light chain (AL amyloidosis is the most common form of systemic amyloid disease, and cardiomyopathy is a dire consequence, resulting in an extremely poor prognosis. AL is characterized by the production of monoclonal free light chains that deposit as amyloid fibrils principally in the heart, liver, and kidneys causing organ dysfunction. We have studied the effects of amyloid fibrils, produced from recombinant λ6 light chain variable domains, on metabolic activity of human cardiomyocytes. The data indicate that fibrils at 0.1 μM, but not monomer, significantly decrease the enzymatic activity of cellular NAD(PH-dependent oxidoreductase, without causing significant cell death. The presence of amyloid fibrils did not affect ATP levels; however, oxygen consumption was increased and reactive oxygen species were detected. Confocal fluorescence microscopy showed that fibrils bound to and remained at the cell surface with little fibril internalization. These data indicate that AL amyloid fibrils severely impair cardiomyocyte metabolism in a dose dependent manner. These data suggest that effective therapeutic intervention for these patients should include methods for removing potentially toxic amyloid fibrils.

  15. Convergent mechanisms favor fast amyloid formation in two lambda 6a Ig light chain mutants.

    Science.gov (United States)

    Valdés-García, Gilberto; Millán-Pacheco, César; Pastor, Nina

    2017-08-01

    Extracellular deposition as amyloids of immunoglobulin light chains causes light chain amyloidosis. Among the light chain families, lambda 6a is one of the most frequent in light chain amyloidosis patients. Its germline protein, 6aJL2, and point mutants, R24G and P7S, are good models to study fibrillogenesis, because their stability and fibril formation characteristics have been described. Both mutations make the germline protein unstable and speed up its ability to aggregate. To date, there is no molecular mechanism that explains how these differences in amyloidogenesis can arise from a single mutation. To look into the structural and dynamical differences in the native state of these proteins, we carried out molecular dynamics simulations at room temperature. Despite the structural similarity of the germline protein and the mutants, we found differences in their dynamical signatures that explain the mutants' increased tendency to form amyloids. The contact network alterations caused by the mutations, though different, converge in affecting two anti-aggregation motifs present in light chain variable domains, suggesting a different starting point for aggregation in lambda chains compared to kappa chains. © 2017 Wiley Periodicals, Inc.

  16. Localized Lymph Node Light Chain Amyloidosis

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    Binod Dhakal

    2015-01-01

    Full Text Available Immunoglobulin-derived light chain amyloidosis can occasionally be associated with localized disease. We present a patient with localized lymph node light chain amyloidosis without an underlying monoclonal protein or lymphoproliferative disorder and review the literature of lymph node amyloidosis discussing work-up and risk factors for systemic progression.

  17. Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

    OpenAIRE

    Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

    2011-01-01

    Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic bindin...

  18. Synchronization in chains of light-controlled oscillators

    International Nuclear Information System (INIS)

    Avila, G M RamIrez; Guisset, J L; Deneubourg, J L

    2005-01-01

    Using light-controlled oscillators (LCOs) and a mathematical model of them introduced in [1], we have analyzed a population of LCOs arranged in chains with nonperiodic (linear configuration) and periodic (ring configuration) boundary conditions in which we have solved numerically the corresponding equations for a broad interval of coupling strength values and for chains between 2 and 25 LCOs. We have considered three different situations, viz. identical LCOs, identical LCOs with simplifications (LCOs considered as integrate-and-fire (IF) oscillators), and finally nonidentical LCOs. We study synchronization under two criteria: the first takes into account the simultaneity of flashing events (phase difference criterion), and the second considers period-locking as a criterion for synchronization. For each case, we have identified regions of synchronization in the plane coupling strength versus number of oscillators. We observe different behaviors depending on the values of these variables

  19. Sequence-Based Discovery Demonstrates That Fixed Light Chain Human Transgenic Rats Produce a Diverse Repertoire of Antigen-Specific Antibodies

    Directory of Open Access Journals (Sweden)

    Katherine E. Harris

    2018-04-01

    Full Text Available We created a novel transgenic rat that expresses human antibodies comprising a diverse repertoire of heavy chains with a single common rearranged kappa light chain (IgKV3-15-JK1. This fixed light chain animal, called OmniFlic, presents a unique system for human therapeutic antibody discovery and a model to study heavy chain repertoire diversity in the context of a constant light chain. The purpose of this study was to analyze heavy chain variable gene usage, clonotype diversity, and to describe the sequence characteristics of antigen-specific monoclonal antibodies (mAbs isolated from immunized OmniFlic animals. Using next-generation sequencing antibody repertoire analysis, we measured heavy chain variable gene usage and the diversity of clonotypes present in the lymph node germinal centers of 75 OmniFlic rats immunized with 9 different protein antigens. Furthermore, we expressed 2,560 unique heavy chain sequences sampled from a diverse set of clonotypes as fixed light chain antibody proteins and measured their binding to antigen by ELISA. Finally, we measured patterns and overall levels of somatic hypermutation in the full B-cell repertoire and in the 2,560 mAbs tested for binding. The results demonstrate that OmniFlic animals produce an abundance of antigen-specific antibodies with heavy chain clonotype diversity that is similar to what has been described with unrestricted light chain use in mammals. In addition, we show that sequence-based discovery is a highly effective and efficient way to identify a large number of diverse monoclonal antibodies to a protein target of interest.

  20. Exploiting light chains for the scalable generation and platform purification of native human bispecific IgG

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    Fischer, Nicolas; Elson, Greg; Magistrelli, Giovanni; Dheilly, Elie; Fouque, Nicolas; Laurendon, Amélie; Gueneau, Franck; Ravn, Ulla; Depoisier, Jean-François; Moine, Valery; Raimondi, Sylvain; Malinge, Pauline; Di Grazia, Laura; Rousseau, François; Poitevin, Yves; Calloud, Sébastien; Cayatte, Pierre-Alexis; Alcoz, Mathias; Pontini, Guillemette; Fagète, Séverine; Broyer, Lucile; Corbier, Marie; Schrag, Delphine; Didelot, Gérard; Bosson, Nicolas; Costes, Nessie; Cons, Laura; Buatois, Vanessa; Johnson, Zoe; Ferlin, Walter; Masternak, Krzysztof; Kosco-Vilbois, Marie

    2015-01-01

    Bispecific antibodies enable unique therapeutic approaches but it remains a challenge to produce them at the industrial scale, and the modifications introduced to achieve bispecificity often have an impact on stability and risk of immunogenicity. Here we describe a fully human bispecific IgG devoid of any modification, which can be produced at the industrial scale, using a platform process. This format, referred to as a κλ-body, is assembled by co-expressing one heavy chain and two different light chains, one κ and one λ. Using ten different targets, we demonstrate that light chains can play a dominant role in mediating specificity and high affinity. The κλ-bodies support multiple modes of action, and their stability and pharmacokinetic properties are indistinguishable from therapeutic antibodies. Thus, the κλ-body represents a unique, fully human format that exploits light-chain variable domains for antigen binding and light-chain constant domains for robust downstream processing, to realize the potential of bispecific antibodies. PMID:25672245

  1. Characterization of myosin light chain in shrimp hemocytic phagocytosis.

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    Han, Fang; Wang, Zhiyong; Wang, Xiaoqing

    2010-11-01

    Myosin light chain, a well-known cytoskeleton gene, regulates multiple processes that are involved in material transport, muscle shrink and cell division. However, its function in phagocytosis against invading pathogens in crustacean remains unknown. In this investigation, a myosin light chain gene was obtained from Marsupenaeus japonicus shrimp. The full-length cDNA of this gene was of 766 bp and an open reading frame (ORF) of 462 bp encoding a polypeptide of 153 amino acids. The myosin light chain protein was expressed in Escherichia coli and purified. Subsequently the specific antibody was raised using the purified GST fusion protein. As revealed by immuno-electron microscopy, the myosin light chain protein was only expressed in the dark bands of muscle. In the present study, the myosin light chain gene was up-regulated in the WSSV-resistant shrimp as revealed by real-time PCR and western blot. And the phagocytic percentage and phagocytic index using FITC-labeled Vibrio parahemolyticus were remarkably increased in the WSSV-resistant shrimp, suggesting that the myosin light chain protein was essential in hemocytic phagocytosis. On the other hand, RNAi assays indicated that the phagocytic percentage and phagocytic index were significantly decreased when the myosin light chain gene was silenced by sequence-specific siRNA. These findings suggested that myosin light chain protein was involved in the regulation of hemocytic phagocytosis of shrimp. Copyright 2010 Elsevier Ltd. All rights reserved.

  2. Recurrence of light-chain deposition disease after renal transplantation

    DEFF Research Database (Denmark)

    Larsen, Thomas; Hammer, Anne; Jørgensen, Kaj Anker

    2008-01-01

    A 51-year-old male with a history of chronic renal disease received a renal allograft, in which disease recurred. Light-chain deposition disease was confirmed through biopsies of the native kidney and graft, and detection of free kappa light chains in serum. Udgivelsesdato: 2007-Sep-6......A 51-year-old male with a history of chronic renal disease received a renal allograft, in which disease recurred. Light-chain deposition disease was confirmed through biopsies of the native kidney and graft, and detection of free kappa light chains in serum. Udgivelsesdato: 2007-Sep-6...

  3. Stretch activates myosin light chain kinase in arterial smooth muscle

    International Nuclear Information System (INIS)

    Barany, K.; Rokolya, A.; Barany, M.

    1990-01-01

    Stretching of porcine carotid arterial muscle increased the phosphorylation of the 20 kDa myosin light chain from 0.23 to 0.68 mol [32P]phosphate/mol light chain, whereas stretching of phorbol dibutyrate treated muscle increased the phosphorylation from 0.30 to 0.91 mol/mol. Two-dimensional gel electrophoresis followed by two-dimensional tryptic phosphopeptide mapping was used to identify the enzyme involved in the stretch-induced phosphorylation. Quantitation of the [32P]phosphate content of the peptides revealed considerable light chain phosphorylation by protein kinase C only in the phorbol dibutyrate treated arterial muscle, whereas most of the light chain phosphorylation was attributable to myosin light chain kinase. Upon stretch of either the untreated or treated muscle, the total increment in [32P]phosphate incorporation into the light chain could be accounted for by peptides characteristic for myosin light chain kinase catalyzed phosphorylation, demonstrating that the stretch-induced phosphorylation is caused by this enzyme exclusively

  4. Serum Free Light Chains

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    ... lab's website in order to provide you with background information about the test(s) you had performed. You will need to return ... the free light chains have a much shorter half-life (3-5 hours) than ... cell disorders, the test is also used for assessing response and minimal ...

  5.  Variable fragments of heavy chain antibodies (VHHs: a new magic bullet molecule of medicine?

    Directory of Open Access Journals (Sweden)

    Dorota Smolarek

    2012-06-01

    Full Text Available  Serum of animals belonging to the Camelidae family (camels and llamas contains fully active antibodies that are naturally devoid of light chains. Variable domains derived from heavy chain antibodies (hcAb called VHHs or nanobodies™ can bind antigens as effectively as full-length antibodies and are easy to clone and express. Because of their potential, VHHs are being intensively studied as potential therapeutic, diagnostic and imaging tools. The paper reviews the molecular background of heavy chain antibodies and describes methods of obtaining recombinant fragments of heavy chain antibodies as well as their therapeutic, diagnostic and other applications.

  6. Myosin light chain kinase phosphorylation in tracheal smooth muscle

    International Nuclear Information System (INIS)

    Stull, J.T.; Hsu, L.C.; Tansey, M.G.; Kamm, K.E.

    1990-01-01

    Purified myosin light chain kinase from smooth muscle is phosphorylated by cyclic AMP-dependent protein kinase, protein kinase C, and the multifunctional calmodulin-dependent protein kinase II. Because phosphorylation in a specific site (site A) by any one of these kinases desensitizes myosin light chain kinase to activation by Ca2+/calmodulin, kinase phosphorylation could play an important role in regulating smooth muscle contractility. This possibility was investigated in 32 P-labeled bovine tracheal smooth muscle. Treatment of tissues with carbachol, KCl, isoproterenol, or phorbol 12,13-dibutyrate increased the extent of kinase phosphorylation. Six primary phosphopeptides (A-F) of myosin light chain kinase were identified. Site A was phosphorylated to an appreciable extent only with carbachol or KCl, agents which contract tracheal smooth muscle. The extent of site A phosphorylation correlated to increases in the concentration of Ca2+/calmodulin required for activation. These results show that cyclic AMP-dependent protein kinase and protein kinase C do not affect smooth muscle contractility by phosphorylating site A in myosin light chain kinase. It is proposed that phosphorylation of myosin light chain kinase in site A in contracting tracheal smooth muscle may play a role in the reported desensitization of contractile elements to activation by Ca2+

  7. Diversity of immunoglobulin lambda light chain gene usage over developmental stages in the horse.

    Science.gov (United States)

    Tallmadge, Rebecca L; Tseng, Chia T; Felippe, M Julia B

    2014-10-01

    To further studies of neonatal immune responses to pathogens and vaccination, we investigated the dynamics of B lymphocyte development and immunoglobulin (Ig) gene diversity. Previously we demonstrated that equine fetal Ig VDJ sequences exhibit combinatorial and junctional diversity levels comparable to those of adult Ig VDJ sequences. Herein, RACE clones from fetal, neonatal, foal, and adult lymphoid tissue were assessed for Ig lambda light chain combinatorial, junctional, and sequence diversity. Remarkably, more lambda variable genes (IGLV) were used during fetal life than later stages and IGLV gene usage differed significantly with time, in contrast to the Ig heavy chain. Junctional diversity measured by CDR3L length was constant over time. Comparison of Ig lambda transcripts to germline revealed significant increases in nucleotide diversity over time, even during fetal life. These results suggest that the Ig lambda light chain provides an additional dimension of diversity to the equine Ig repertoire. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Light-switching-light optical transistor based on metallic nanoparticle cross-chains geometry incorporating Kerr nonlinearity

    Energy Technology Data Exchange (ETDEWEB)

    AbdelMalek, Fathi; Aroua, Walid [National Institute of Applied Science and Technology, University of Carthage, Tunis (Tunisia); Haxha, Shyqyri [Computer Science and Technology Department, Bedfordshire University, Luton (United Kingdom); Flint, Ian [Selex ES Ltd, Luton, Bedfordshire (United Kingdom)

    2016-08-15

    In this research work, we propose all-optical transistor based on metallic nanoparticle cross-chains geometry. The geometry of the proposed device consists of two silver nanoparticle chains arranged along the x- and z-axis. The x-chain contains a Kerr nonlinearity, the source beam is set at the left side of the later, while the control beam is located at the top side of the z-chain. The control beam can turn ON and OFF the light transmission of an incoming light. We report a theoretical model of a very small all-optical transistor proof-of-concept made of optical 'light switching light' concept. We show that the transmission efficiency strongly depends on the control beam and polarization of the incoming light. We investigate the influence of a perfect reflector and reflecting substrate on the transmission of the optical signal when the control beam is turned ON and OFF. These new findings make our unique design a potential candidate for future highly-integrated optical information processing chips. (copyright 2016 by WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  9. Myeloma-Derived Light Chain Paired with a Diagnostic Monoclonal Antibody Hinders Immunoassay Performance.

    Science.gov (United States)

    Tu, Bailin; Tieman, Bryan; Moore, Jeffrey; Pan, You; Muerhoff, A Scott

    2017-06-01

    Monoclonal antibodies are widely used as the capture and detection reagents in diagnostic immunoassays. In the past, myeloma fusion partners expressing endogenous heavy and/or light chains were often used to generate hybridoma cell lines. As a result, mixed populations of antibodies were produced that can cause inaccurate test results, poor antibody stability, and significant lot-to-lot variability. We describe one such scenario where the P3U1 (P3X63Ag8U.1) myeloma fusion partner was used in the generation of a hybridoma producing protein induced vitamin K absence/antagonist-II (PIVKA II) antibody. The hybridoma produces three subpopulations of immunoglobulin as determined by ion exchange (IEx) chromatography that exhibit varying degrees of immunoreactivity (0%, 50%, or 100%) to the target antigen as determined by Surface Plasmon Resonance. To produce an antibody with the highest possible sensitivity and specificity, the antigen-specific heavy and light chain variable domains (VH and VL) were cloned from the hybridoma and tethered to murine IgG1 and kappa scaffolds. The resulting recombinant antibody was expressed in Chinese hamster ovary cells and is compatible for use in a diagnostic immunoassay.

  10. An enzyme immunoassay to quantify neurofilament light chain in cerebrospinal fluid.

    NARCIS (Netherlands)

    Geel, W.J.A. van; Rosengren, L.E.; Verbeek, M.M.

    2005-01-01

    Neurofilament light chain is a component of the axonal cytoskeleton. The concentration of the neurofilament light chain in cerebrospinal fluid may reflect axonal damage or the extent of white matter damage. In this study we describe a sensitive immunoassay for the detection of neurofilament light

  11. Serum Immunoglobulin Free Light Chain Assessment in IgG4-Related Disease

    Directory of Open Access Journals (Sweden)

    Aurélie Grados

    2013-01-01

    Full Text Available Immunoglobulin free light chains are produced in excess during normal antibody synthesis. Their evaluation is commonly used in case of a monoclonal gammopathy. In polyclonal hypergammaglobulinemia related to the Sjögren syndrome or systemic lupus, erythematosus serum free light chain levels are increased and could correlate with disease activity. We show here that the κ ( and λ ( free light chains and the κ : λ ratio ( are increased in sixteen patients with IgG4-related disease when compared to healthy controls. The increase of κ and λ free light chains probably reflects the marked polyclonal B cell activation of the disease. We could not assess in this small cohort of patients a significative correlation of serum free light chain levels and disease activity or extension.

  12. Myosin Light Chain Kinase and the Role of Myosin Light Chain Phosphorylation in Skeletal Muscle

    Science.gov (United States)

    Stull, James T.; Kamm, Kristine E.; Vandenboom, Rene

    2011-01-01

    Skeletal muscle myosin light chain kinase (skMLCK) is a dedicated Ca2+/calmodulin-dependent serine-threonine protein kinase that phosphorylates the regulatory light chain (RLC) of sarcomeric myosin. It is expressed from the MYLK2 gene specifically in skeletal muscle fibers with most abundance in fast contracting muscles. Biochemically, activation occurs with Ca2+ binding to calmodulin forming a (Ca2+)4•calmodulin complex sufficient for activation with a diffusion limited, stoichiometic binding and displacement of a regulatory segment from skMLCK catalytic core. The N-terminal sequence of RLC then extends through the exposed catalytic cleft for Ser15 phosphorylation. Removal of Ca2+ results in the slow dissociation of calmodulin and inactivation of skMLCK. Combined biochemical properties provide unique features for the physiological responsiveness of RLC phosphorylation, including (1) rapid activation of MLCK by Ca2+/calmodulin, (2) limiting kinase activity so phosphorylation is slower than contraction, (3) slow MLCK inactivation after relaxation and (4) much greater kinase activity relative to myosin light chain phosphatase (MLCP). SkMLCK phosphorylation of myosin RLC modulates mechanical aspects of vertebrate skeletal muscle function. In permeabilized skeletal muscle fibers, phosphorylation-mediated alterations in myosin structure increase the rate of force-generation by myosin cross bridges to increase Ca2+-sensitivity of the contractile apparatus. Stimulation-induced increases in RLC phosphorylation in intact muscle produces isometric and concentric force potentiation to enhance dynamic aspects of muscle work and power in unfatigued or fatigued muscle. Moreover, RLC phosphorylation-mediated enhancements may interact with neural strategies for human skeletal muscle activation to ameliorate either central or peripheral aspects of fatigue. PMID:21284933

  13. Super-light pearl-chain arch vaults

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl; Halding, Philip Skov

    2014-01-01

    Arch vaults are known as optimal and impressive structures, but due to their curved shapes they are extremely costly to produce in countries, where the cost of labor is high. By means of super-light pearl-chain technology arch vaults can be constructed from equal plane prefabricated elements, which...... that it is also applicable as basic elements for super-light pearl-chain vaults. Machines and software have been developed for automatic mass production of the elements, and the first factory has started production in Denmark in 2014 delivering SL-deck elements for a variety of building projects. This means...... is known from curved voluminous elements. The paper describes the first full-scale test of an arch vault made of SL-deck elements demonstrating the principle, documenting the load-bearing capacity, and solving a number of details needed in order to create vaults in practice. Considerations and plans...

  14. Chimeric Anti-Human Podoplanin Antibody NZ-12 of Lambda Light Chain Exerts Higher Antibody-Dependent Cellular Cytotoxicity and Complement-Dependent Cytotoxicity Compared with NZ-8 of Kappa Light Chain.

    Science.gov (United States)

    Kaneko, Mika K; Abe, Shinji; Ogasawara, Satoshi; Fujii, Yuki; Yamada, Shinji; Murata, Takeshi; Uchida, Hiroaki; Tahara, Hideaki; Nishioka, Yasuhiko; Kato, Yukinari

    2017-02-01

    Podoplanin (PDPN), a type I transmembrane 36-kDa glycoprotein, is expressed not only in normal cells, such as renal epithelial cells (podocytes), lymphatic endothelial cells, and pulmonary type I alveolar cells, but also in cancer cells, including brain tumors and lung squamous cell carcinomas. Podoplanin activates platelet aggregation by binding to C-type lectin-like receptor-2 (CLEC-2) on platelets, and the podoplanin/CLEC-2 interaction facilitates blood/lymphatic vessel separation. We previously produced neutralizing anti-human podoplanin monoclonal antibody (mAb), clone NZ-1 (rat IgG 2a , lambda), which neutralizes the podoplanin/CLEC-2 interaction and inhibits platelet aggregation and cancer metastasis. Human-rat chimeric antibody, NZ-8, was previously developed using variable regions of NZ-1 and human constant regions of heavy chain (IgG 1 ) and light chain (kappa chain). Although NZ-8 showed high antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against human podoplanin-expressing cancer cells, the binding affinity of NZ-8 was lower than that of NZ-1. Herein, we produced a novel human-rat chimeric antibody, NZ-12, the constant regions of which consist of IgG 1 heavy chain and lambda light chain. Using flow cytometry, we demonstrated that the binding affinity of NZ-12 was much higher than that of NZ-8. Furthermore, ADCC and CDC activities of NZ-12 were significantly increased against glioblastoma cell lines (LN319 and D397) and lung cancer cell line (PC-10). These results suggested that NZ-12 could become a promising therapeutic antibody against podoplanin-expressing brain tumors and lung cancers.

  15. Super-light Structures with Pearl-chain Reinforcement

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl; Bagger, Anne

    2010-01-01

    Steel structures are considered to be light compared to concrete structures. This paper presents a newly invented type of structure which is often light compared to steel structures, and therefore it is called "Super-light Structures", or SLS. The basic idea of SLS is to build a skeleton...... of prefabricated segments of a strong material, assembled by one or more prestressing wires. By means of pearl-chain reinforcement, it becomes affordable to provide structures with a wide variety of shapes. This allows a more resource-economical design, because it removes practical hindrances for application...

  16. Prognostic value of depressed midwall systolic function in cardiac light-chain amyloidosis.

    Science.gov (United States)

    Perlini, Stefano; Salinaro, Francesco; Musca, Francesco; Mussinelli, Roberta; Boldrini, Michele; Raimondi, Ambra; Milani, Paolo; Foli, Andrea; Cappelli, Francesco; Perfetto, Federico; Palladini, Giovanni; Rapezzi, Claudio; Merlini, Giampaolo

    2014-05-01

    Cardiac amyloidosis represents an archetypal form of restrictive heart disease, characterized by profound diastolic dysfunction. As ejection fraction is preserved until the late stage of the disease, the majority of patients do fulfill the definition of diastolic heart failure, that is, heart failure with preserved ejection fraction (HFpEF). In another clinical model of HFpEF, that is, pressure-overload hypertrophy, depressed midwall fractional shortening (mFS) has been shown to be a powerful prognostic factor. To assess the potential prognostic role of mFS in cardiac light-chain amyloidosis with preserved ejection fraction, we enrolled 221 consecutive untreated patients, in whom a first diagnosis of cardiac light-chain amyloidosis was concluded between 2008 and 2010. HFpEF was present in 181 patients. Patients in whom cardiac involvement was excluded served as controls (n = 121). Prognosis was assessed after a median follow-up of 561 days. When compared with light-chain amyloidosis patients without myocardial involvement, cardiac light-chain amyloidosis was characterized by increased wall thickness (P model. In cardiac light-chain amyloidosis with normal ejection fraction, depressed circumferential mFS, a marker of myocardial contractile dysfunction, is a powerful predictor of survival.

  17. [A wrong move in an amateur football player reveals a light chain myeloma].

    Science.gov (United States)

    Peyneau, Marine; Nassiri, Shiva; Myara, Anne; Ohana, Salomon; Laplanche, Sophie

    2016-01-01

    Light chain multiple myeloma is a hematologic malignancy characterized by an excess of tumor plasma cells in the bone marrow and a monoclonal light chain in blood. It is generally diagnosed in patients aged 60-75 years old. Hypercalcemia, anemia, kidney failure, and bone pains are the main clinical and biological signs. Here is an atypical case report about a 30 year-old man who was diagnosed a light chain multiple myeloma. This patient had been suffering from back pain for 5 months. Osteolytic lesions were discovered on X-rays prescribed by the family practitioner. Admitted to the Emergency department, all blood tests showed results within the normal range. The serum protein electrophoresis was also normal. Only the urine analysis showed proteinuria. The urine immunofixation electrophoresis showed a massive κ light chain. The bone marrow aspiration cell count confirmed the myeloma diagnosis with an infiltration of dystrophic plasma cells. The patient was transferred to the hematology ward of Necker Hospital for treatment of light chain myeloma.

  18. MAK33 antibody light chain amyloid fibrils are similar to oligomeric precursors.

    Directory of Open Access Journals (Sweden)

    Manuel Hora

    Full Text Available Little structural information is available so far on amyloid fibrils consisting of immunoglobulin light chains. It is not understood which features of the primary sequence of the protein result in fibril formation. We report here MAS solid-state NMR studies to identify the structured core of κ-type variable domain light chain fibrils. The core contains residues of the CDR2 and the β-strands D, E, F and G of the native immunoglobulin fold. The assigned core region of the fibril is distinct in comparison to the core identified in a previous solid-state NMR study on AL-09 by Piehl at. al, suggesting that VL fibrils can adopt different topologies. In addition, we investigated a soluble oligomeric intermediate state, previously termed the alternatively folded state (AFS, using NMR and FTIR spectroscopy. The NMR oligomer spectra display a high degree of similarity when compared to the fibril spectra, indicating a high structural similarity of the two aggregation states. Based on comparison to the native state NMR chemical shifts, we suggest that fibril formation via domain-swapping seems unlikely. Moreover, we used our results to test the quality of different amyloid prediction algorithms.

  19. Generation of human Fab antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human Fab (fragment antigen binding) antibody libraries. In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final Fab products that are used for cloning.

  20. Verification of serum reference intervals for free light chains in a local South African population.

    Science.gov (United States)

    Zemlin, Annalise E; Rensburg, Megan A; Ipp, Hayley; Germishuys, Jurie J; Erasmus, Rajiv T

    2013-11-01

    Monoclonal serum free light chain measurements are used to follow up and manage patients with monoclonal gammopathies, and abnormal serum free light chain ratios are associated with risk of progression in certain diseases. We aimed to validate the reference intervals in our population. Reference intervals for κ and λ free light chains were established on 120 healthy adults. Creatinine levels were measured to exclude renal dysfunction and serum protein electrophoresis was performed. All creatinine values were within normal limits. After exclusion of subjects with abnormal serum protein electrophoreses, 113 subjects were available for analysis. The 95% reference interval was 6.3-20.6 mg/L for κ free light chains, 8.7-25.9 mg/L for λ free light chains and 0.46-1.23 for free light chain ratio. Most of the values fell within the manufacturer's recommended limits and therefore could be used for our population.

  1. Optimization of Serum Immunoglobulin Free Light Chain Analysis for Subclassification of Cardiac Amyloidosis.

    Science.gov (United States)

    Halushka, Marc K; Eng, George; Collins, A Bernard; Judge, Daniel P; Semigran, Marc J; Stone, James R

    2015-06-01

    Accurate and rapid classification of cardiac amyloidosis is important for patient management. We have optimized the use of serum free light chain kappa and lambda values to differentiate immunoglobulin light chain amyloid (AL) amyloidosis from transthyretin amyloid and amyloid A using 85 cases of tissue-proven cardiac amyloidosis, in which there was direct classification of amyloidosis by mass spectrometry or immunofluorescence. The serum free light chain kappa/lambda ratios were non-overlapping for the three major groups: AL-lambda (0.01-0.41, n = 30), non-AL (0.52-2.7, n = 43), and AL-kappa (6.7-967, n = 12). A kappa/lambda ratio value between 0.5 and 5.0 had 100 % sensitivity and 100 % specificity for distinguishing AL amyloidosis from non-AL amyloidosis. This optimized range for serum light chain kappa/lambda ratio provides extremely robust classification of cardiac amyloidosis. Cases of cardiac amyloidosis in which the serum kappa/lambda free light chain ratio falls close to these new cutoff values may benefit most from direct amyloid subtyping.

  2. Light-assisted, templated self-assembly of gold nanoparticle chains.

    Science.gov (United States)

    Jaquay, Eric; Martínez, Luis Javier; Huang, Ningfeng; Mejia, Camilo A; Sarkar, Debarghya; Povinelli, Michelle L

    2014-09-10

    We experimentally demonstrate the technique of light-assisted, templated self-assembly (LATS) to trap and assemble 200 nm diameter gold nanoparticles. We excite a guided-resonance mode of a photonic-crystal slab with 1.55 μm laser light to create an array of optical traps. Unlike our previous demonstration of LATS with polystyrene particles, we find that the interparticle interactions play a significant role in the resulting particle patterns. Despite a two-dimensionally periodic intensity profile in the slab, the particles form one-dimensional chains whose orientations can be controlled by the incident polarization of the light. The formation of chains can be understood in terms of a competition between the gradient force due to the excitation of the mode in the slab and optical binding between particles.

  3. Generation of human scFv antibody libraries: PCR amplification and assembly of light- and heavy-chain coding sequences.

    Science.gov (United States)

    Andris-Widhopf, Jennifer; Steinberger, Peter; Fuller, Roberta; Rader, Christoph; Barbas, Carlos F

    2011-09-01

    The development of therapeutic antibodies for use in the treatment of human diseases has long been a goal for many researchers in the antibody field. One way to obtain these antibodies is through phage-display libraries constructed from human lymphocytes. This protocol describes the construction of human scFv (single chain antibody fragment) libraries using a short linker (GGSSRSS) or a long linker (GGSSRSSSSGGGGSGGGG). In this method, the individual rearranged heavy- and light-chain variable regions are amplified separately and are linked through a series of overlap polymerase chain reaction (PCR) steps to give the final scFv products that are used for cloning.

  4. Primary CNS Nonamyloidogenic Light Chain Deposition Disease: Case Report and Brief Review.

    Science.gov (United States)

    Mercado, Juan Jose; Markert, James M; Meador, William; Chapman, Philip; Perry, Arie; Hackney, James R

    2017-12-01

    The true incidence of light chain deposition disease (LCDD) restricted to the central nervous system (CNS) is unknown. To our knowledge only 7 cases of LCDD restricted to the brain have been previously reported. We herein describe an unusual example. A 44-year-old man presented with a history of ischemic retinopathy in 2004 and left lower extremity hypoesthesia in 2007 that progressed gradually to left-sided weakness and numbness in the 2 years prior to his hospitalization in 2015. A stereotactic brain biopsy was performed, displaying nonspecific hyaline deposits of amorphous "amyloid-like" material involving deep brain white matter and vessels. These were Congo red negative and were accompanied by a sparse lymphoplasmacytic infiltrate. Plasma cells demonstrated kappa light chain class restriction by chromogenic in situ hybridization (CISH). There was patchy reactivity with kappa immunohistochemistry in the amorphous deposits. A diagnosis of light chain deposition disease was made. Subsequent systemic myeloma and lymphoma workups were negative. Previously reported cases have included men and women, spanning the ages of 19 and 72 years, often presenting with hemiparesis, hypoesthesia, or seizures. Deposits have been reported in the cerebrum and cerebellum. T2/FLAIR (fluid attenuation inversion recovery) changes are usual, but lesions may or may not produce contrast enhancement. The light chain deposition may be of kappa or lambda class. Most lesions have been accompanied by local lymphoid and/or plasma cell infiltrates exhibiting light chain restriction of the same class as the deposits. In summary, LCDD limited to the CNS is a rare lesion consisting of deposition of amyloid-like, but Congo red-negative monotypic light chain usually produced by local lymphoplasmacytic infiltrates.

  5. Light chain deposition disease in multiple myeloma: MR imaging features correlated with histopathological findings

    International Nuclear Information System (INIS)

    Baur, A.; Staebler, A.; Reiser, M.; Lamerz, R.; Bartl, R.

    1998-01-01

    The clinical, histopathological, and imaging findings on MRI of a 56-year-old woman with light chain deposition disease occurring in multiple myeloma are presented. Light chain deposition disease is a variant of multiple myeloma with distinct clinical and histological characteristics. MRI of this patient also revealed an infiltration pattern in the bone marrow distinct from that of typical multiple myeloma. Multiple small foci of low signal intensity were present on T1- and T2-weighted spin echo and STIR images, corresponding to conglomerates of light chains in bone marrow biopsy. Contrast-enhanced T1-weighted spin echo images show diffuse enhancement of 51% over all vertebral bodies, with a minor enhancement of the focal conglomerates of light chains. Light chain deposition disease in multiple myeloma should be added to the list of those few entities with normal radiographs and discrete low-signal marrow lesions on T1- and T2-weighted spin echo pulse sequences. (orig.)

  6. Light chain (AL amyloidosis: update on diagnosis and management

    Directory of Open Access Journals (Sweden)

    Rosenzweig Michael

    2011-11-01

    Full Text Available Abstract Light chain (AL amyloidosis is a plasma cell dyscrasia characterized by the pathologic production of fibrillar proteins comprised of monoclonal light chains which deposit in tissues and cause organ dysfunction. The diagnosis can be challenging, requiring a biopsy and often specialized testing to confirm the subtype of systemic disease. The goal of treatment is eradication of the monoclonal plasma cell population and suppression of the pathologic light chains which can result in organ improvement and extend patient survival. Standard treatment approaches include high dose melphalan (HDM followed by autologous hematopoietic stem cell transplantation (SCT or oral melphalan with dexamethasone (MDex. The use of novel agents (thalidomide, lenalidomide and bortezomib alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. A risk adapted approach to SCT followed by novel agents as consolidation reduces treatment related mortality with promising outcomes. Immunotherapeutic approaches targeting pathologic plasma cells and amyloid precursor proteins or fibrils are being developed. Referral of patients to specialized centers focusing on AL amyloidosis and conducting clinical trials is essential to improving patient outcomes.

  7. Myosin light chain kinase regulates synaptic plasticity and fear learning in the lateral amygdala.

    Science.gov (United States)

    Lamprecht, R; Margulies, D S; Farb, C R; Hou, M; Johnson, L R; LeDoux, J E

    2006-01-01

    Learning and memory depend on signaling molecules that affect synaptic efficacy. The cytoskeleton has been implicated in regulating synaptic transmission but its role in learning and memory is poorly understood. Fear learning depends on plasticity in the lateral nucleus of the amygdala. We therefore examined whether the cytoskeletal-regulatory protein, myosin light chain kinase, might contribute to fear learning in the rat lateral amygdala. Microinjection of ML-7, a specific inhibitor of myosin light chain kinase, into the lateral nucleus of the amygdala before fear conditioning, but not immediately afterward, enhanced both short-term memory and long-term memory, suggesting that myosin light chain kinase is involved specifically in memory acquisition rather than in posttraining consolidation of memory. Myosin light chain kinase inhibitor had no effect on memory retrieval. Furthermore, ML-7 had no effect on behavior when the training stimuli were presented in a non-associative manner. Anatomical studies showed that myosin light chain kinase is present in cells throughout lateral nucleus of the amygdala and is localized to dendritic shafts and spines that are postsynaptic to the projections from the auditory thalamus to lateral nucleus of the amygdala, a pathway specifically implicated in fear learning. Inhibition of myosin light chain kinase enhanced long-term potentiation, a physiological model of learning, in the auditory thalamic pathway to the lateral nucleus of the amygdala. When ML-7 was applied without associative tetanic stimulation it had no effect on synaptic responses in lateral nucleus of the amygdala. Thus, myosin light chain kinase activity in lateral nucleus of the amygdala appears to normally suppress synaptic plasticity in the circuits underlying fear learning, suggesting that myosin light chain kinase may help prevent the acquisition of irrelevant fears. Impairment of this mechanism could contribute to pathological fear learning.

  8. Neurofilament light chain and oligoclonal bands are prognostic biomarkers in radiologically isolated syndrome.

    Science.gov (United States)

    Matute-Blanch, Clara; Villar, Luisa M; Álvarez-Cermeño, José C; Rejdak, Konrad; Evdoshenko, Evgeniy; Makshakov, Gleb; Nazarov, Vladimir; Lapin, Sergey; Midaglia, Luciana; Vidal-Jordana, Angela; Drulovic, Jelena; García-Merino, Antonio; Sánchez-López, Antonio J; Havrdova, Eva; Saiz, Albert; Llufriu, Sara; Alvarez-Lafuente, Roberto; Schroeder, Ina; Zettl, Uwe K; Galimberti, Daniela; Ramió-Torrentà, Lluís; Robles, René; Quintana, Ester; Hegen, Harald; Deisenhammer, Florian; Río, Jordi; Tintoré, Mar; Sánchez, Alex; Montalban, Xavier; Comabella, Manuel

    2018-04-01

    The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid

  9. Characterization of the interaction between the heavy and light chains of bovine factor Va.

    Science.gov (United States)

    Walker, F J

    1992-10-05

    Bovine factor Va has been previously been shown to consist of heavy (M(r) = 94,000) and light chains (M(r) = 81,000), that interact in a manner dependent upon the presence of either calcium or manganese ions. In an attempt to understand the mechanism of subunit interaction we have studied the effects of temperature and ions on factor Va stability. The rates of formation of factor Va from isolated chains and dissociation were temperature-dependent with an energy of activation of 6.2 and 1.3 kcal mol-1, respectively. The yield of factor Va from isolated chains was inversely related to the amount of time the chains were incubated at 4 degrees C. Incubation of individual chains revealed that the heavy chain is cold-labile, an effect that is reversible. Manganese ion was observed to prevent the conversion to the inactive form. High salt tends to stabilize the two-chain structure of factor Va, but is inhibitory to its formation from isolated chains. High concentrations of either manganese or calcium ions also inhibited reconstitution of activity. The light chain, in particular, was sensitive to the presence of manganese or calcium ion. Heavy chain that had been cleaved by activated protein C had a weakened interaction with the light chain, and the resulting complex had no procoagulant activity. Cooling of the heavy chain to 4 degrees C enhanced its intrinsic fluorescence. Manganese ion prevented some of this enhancement. The heavy chain fluorescence returned to the room temperature value with a half-life of approximately 10 min. In the presence of manganese ion relaxation was accelerated. The intrinsic fluorescence of activated protein C-cleaved heavy chain was not increased when the temperature was decreased. These data suggest that the heavy chain can exist in two forms. Elevated temperature converts it to a form that can bind ions and have a productive interaction with the light chain. However, conditions that prevent the heavy chain from combining with the light

  10. Acquired cutis laxa associated with light and heavy chain deposition disease

    Directory of Open Access Journals (Sweden)

    Reena A Majithia

    2018-01-01

    Full Text Available Acquired cutis laxa (ACL is a rare connective tissue disorder characterized by pendulous and coarsely wrinkled skin. There have been few cases of its association to monoclonal immunoglobulin deposition disease (MIDD, which constitutes the light chain (LCDD, heavy chain (HCDD, and light and heavy chain (LHCDD deposition disease. MIDD predominantly involves the kidney. Skin is the next common organ to be affected by HCDD, which presents as ACL. We report the case of a 40-year-old male who presented with ACL associated with LHCDD. The clinical features of ACL in the present case appeared prior to the development of clinical features related to LHCDD.

  11. Microscopic theory of light-induced deformation in amorphous side-chain azobenzene polymers.

    Science.gov (United States)

    Toshchevikov, V; Saphiannikova, M; Heinrich, G

    2009-04-16

    We propose a microscopic theory of light-induced deformation of side-chain azobenzene polymers taking into account the internal structure of polymer chains. Our theory is based on the fact that interaction of chromophores with the polarized light leads to the orientation anisotropy of azobenzene macromolecules which is accompanied by the appearance of mechanical stress. It is the first microscopic theory which provides the value of the light-induced stress larger than the yield stress. This result explains a possibility for the inscription of surface relief gratings in glassy side-chain azobenzene polymers. For some chemical architectures, elongation of a sample demonstrates a nonmonotonic behavior with the light intensity and can change its sign (a stretched sample starts to be uniaxially compressed), in agreement with experiments. Using a viscoplastic approach, we show that the irreversible strain of a sample, which remains after the light is switched off, decreases with increasing temperature and can disappear at certain temperature below the glass transition temperature. This theoretical prediction is also confirmed by recent experiments.

  12. Serum free light chain reference values: a critical approach.

    Science.gov (United States)

    Altinier, Sara; Seguso, Mara; Zaninotto, Martina; Varagnolo, Mariacristina; Adami, Fausto; Angeli, Paolo; Plebani, Mario

    2013-05-01

    The clinical usefulness of serum free light chain (FLC) measurement in the management of patients with plasma cell proliferative disorders has been reported in several papers, and most clinical studies use the reference ranges declared by the manufacturer. The aim of the present study was to evaluate the reproducibility of FLCs immunoassay and to validate the reference range, before introducing it in routine setting. Internal quality control materials and a pool of fresh serum samples were used to evaluate imprecision; 162 fresh sera from healthy blood donors were analyzed to evaluate the reference range for FLCs. In order to verify the κ/λ FLC ratio, 43 sera from patients with polyclonal hypergammaglobulinemia were tested. The FLC immunoassay was performed using a nephelometer with the Freelite reagents. The imprecision studies performed using a serum pool tested with two different lots of reagents showed a mean CV of 16.09% for κFLC and of 16.72% for λFLC. Lower CV%s and different mean values were found by calculating the results from each specific lot separately, while different results were obtained using the control materials provided by the manufacturer. In reference subjects, the 2.5-97.5th percentiles were found to be 4.52-22.33 and 4.84-21.88mg/L for κFLC and λFLC, respectively. The range for κ/λ ratio (0.65-2.36) was validated with the values obtained from subjects with polyclonal hypergammaglobulinemia. In retesting 15 samples from blood donor subjects with a different lot of reagents, mean bias percentages of 17.60 for κFLC and 15.26 for λFLC were obtained. These findings confirm the lot-to-lot variability of the FLC assays also in the measurement of polyclonal light chains, as well as the need to carefully validate the reference values. Published by Elsevier Inc.

  13. Effects of Variable Resistance Using Chains on Bench Throw Performance in Trained Rugby Players.

    Science.gov (United States)

    Godwin, Mark S; Fernandes, John F T; Twist, Craig

    2018-04-01

    Godwin, MS, Fernandes, JFT, and Twist, C. Effects of variable resistance using chains on bench throw performance in trained rugby players. J Strength Cond Res 32(4): 950-954, 2018-This study sought to determine the effects of variable resistance using chain resistance on bench throw performance. Eight male rugby union players (19.4 ± 2.3 years, 88.8 ± 6.0 kg, 1RM 105.6 ± 17.0 kg) were recruited from a national league team. In a randomized crossover design, participant's performed 3 bench throws at 45% one repetition maximum (1RM) at a constant load (no chains) or a variable load (30% 1RM constant load and 15% 1RM variable load; chains) with 7 days between conditions. For each repetition, the peak and mean velocity, peak power, peak acceleration, and time to peak velocity were recorded. Differences in peak and mean power were very likely trivial and unclear between the chain and no chain conditions, respectively. Possibly greater peak and likely greater mean bar velocity were accompanied by likely to most likely greater bar velocity between 50 and 400 ms from initiation of bench press in the chain condition compared with the no chain condition. Accordingly, bar acceleration was very likely greater in the chain condition compared with the no chain condition. In conclusion, these results show that the inclusion of chain resistance can acutely enhance several variables in the bench press throw and gives support to this type of training.

  14. Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

    Directory of Open Access Journals (Sweden)

    Tanya L. Poshusta

    2013-11-01

    Full Text Available Light chain (AL amyloidosis is a devastating disease characterized by amyloid deposits formed by immunoglobulin light chains. Current available treatments involve conventional chemotherapy and autologous stem cell transplant. We have recently concluded a phase III trial comparing these two treatments. AL amyloidosis patients who achieve hematological complete response (CR do not necessarily achieve organ response regardless of the treatment they received. In order to investigate the possible correlation between amyloid formation kinetics and organ response, we selected AL amyloidosis patients from the trial with kidney involvement and CR after treatment. Six patients were selected and their monoclonal immunoglobulin light chains were characterized. The proteins showed differences in their stability and their kinetics of amyloid formation. A correlation was detected at pH 7.4, showing that less stable proteins are more likely to form amyloid fibrils. AL-T03 is too unstable to form amyloid fibrils at pH 7.4. This protein was found in the only patient in the study that had organ response, suggesting that partially folded species are required for amyloid formation to occur in AL amyloidosis.

  15. Light scattering of thin azobenzene side-chain polyester layers

    DEFF Research Database (Denmark)

    Kerekes, Á.; Lörincz, E.; Ramanujam, P.S.

    2002-01-01

    Light scattering properties of liquid crystalline and amorphous azobenzene side-chain polyester layers used for optical data storage were examined by means of transmissive scatterometry. Comparative experiments show that the amorphous polyester has significantly lower light scattering...... characteristics than the liquid crystalline polyester. The amorphous samples have negligible polarization part orthogonal to the incident beam. the liquid crystalline samples have relative high orthogonal polarization part in light scattering, The light scattering results can be used to give a lower limit...... for the domain size in thin liquid crystalline polyester layers being responsible for the dominant light scattering. The characteristic domain Sizes obtained from the Fourier transformation of polarization microscopic Pictures confirm these values....

  16. The Clinical Presentation and Management of Systemic Light-Chain Amyloidosis in China.

    Science.gov (United States)

    Huang, Xiang-Hua; Liu, Zhi-Hong

    2016-04-01

    Amyloidosis includes a group of diseases characterized by the extracellular deposition of various fibrillary proteins that can autoaggregate in a highly abnormal fibrillary conformation. The amyloid precursor protein of systemic light-chain (AL) amyloidosis is comprised of monoclonal light chains that are due to plasma cell dyscrasia. The clinical presentation of patients with AL amyloidosis varies from patient to patient. Current treatment strategies target the clone in order to decrease the production of the pathologic light chains. Recent advances in therapy have helped many patients with AL amyloidosis achieve hematologic and organ responses. AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The clinical presentation of AL amyloidosis is variable, and the median overall survival was found to be 36.3 months. The disease prognosis and risk stratification are linked to serialized measurement of cardiac biomarkers and free light chains. The treatment of AL amyloidosis is mainly based on chemotherapy and autologous hematopoietic stem cell transplantation (ASCT). The use of novel agents (thalidomide, lenalidomide, and bortezomib) alone and in combination with steroids and alkylating agents has shown efficacy and continues to be explored. AL amyloidosis is the most common type of systemic amyloidosis in China with increasing morbidity and a high mortality rate. The lack of prospective clinical trials using the current therapies is a challenge for evidence-based decision making concerning the treatment of AL amyloidosis. (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At

  17. K-252a, a novel microbial product, inhibits smooth muscle myosin light chain kinase

    International Nuclear Information System (INIS)

    Nakanishi, S.; Yamada, K.; Kase, H.; Nakamura, S.; Nonomura, Y.

    1988-01-01

    Effects of K-252a, purified from the culture broth of Nocardiopsis sp., on the activity of myosin (light chain kinase were investigated. 1) K-252a affected three characteristic properties of chicken gizzard myosin-B, natural actomyosin, to a similar degree: the Ca 2+ -dependent activity of ATPase, superprecipitation, and the phosphorylation of the myosin light chain. 2) K-252a inhibited the activities of the purified myosin light chain kinase and a Ca 2+ -independent form of the enzyme which was constructed by cross-linking of myosin light chain kinase and calmodulin using glutaraldehyde. The degrees of inhibition by 3 x 10 -6 M K-252a were 69 and 48% of the control activities with the purified enzyme and the cross-linked complex, respectively. Chlorpromazine (3 x 10 -4 M), a calmodulin antagonist, inhibited the native enzyme, but not the cross-linked one. These results suggested that K-252a inhibited myosin light chain kinase by direct interaction with the enzyme, whereas chlorpromazine suppressed the enzyme activation by interacting with calmodulin. 3) The inhibition by K-252a of the cross-linked kinase was affected by the concentration of ATP, a phosphate donor. The concentration causing 50% inhibition was two orders magnitude lowere in the presence of 100 μM ATP than in the presence of 2 mM ATP. 4) Kinetic analyses using [γ- 32 P]ATP indicated that the inhibitory mode of K-252a was competitive with respect to ATP. These results suggest that K-252a interacts at the ATP-binding domain of myosin light chain kinase

  18. B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains.

    Science.gov (United States)

    Slot, Linda M; Hoogeboom, Robbert; Smit, Laura A; Wormhoudt, Thera A M; Biemond, Bart J; Oud, Monique E C M; Schilder-Tol, Esther J M; Mulder, André B; Jongejan, Aldo; van Kampen, Antoine H C; Kluin, Philip M; Guikema, Jeroen E J; Bende, Richard J; van Noesel, Carel J M

    2016-12-01

    Follicular lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma able to transform into germinal center-type diffuse large B-cell lymphoma. We describe four extraordinary cases of FL, which progressed to TdT + CD20 - precursor B-lymphoblastic lymphoma (B-LBL). Fluorescence in situ hybridization analysis showed that all four B-LBLs had acquired a MYC translocation on transformation. Comparative genomic hybridization analysis of one case demonstrated that in addition to 26 numerical aberrations that were shared between the FL and B-LBL, deletion of CDKN2A/B and 17q11, 14q32 amplification, and copy-neutral loss of heterozygosity of 9p were gained in the B-LBL cells. Whole-exome sequencing revealed mutations in FMN2, NEB, and SYNE1 and a nonsense mutation in KMT2D, all shared by the FL and B-LBL, and TNFRSF14, SMARCA2, CCND3 mutations uniquely present in the B-LBL. Remarkably, all four FL-B-LBL pairs expressed IgG. In two B-LBLs, evidence was obtained for ongoing rearrangement of IG light chain variable genes and expression of the surrogate light chain. IGHV mutation analysis showed that all FL-B-LBL pairs harbored identical or near-identical somatic mutations. From the somatic gene alterations found in the IG and non-IG genes, we conclude that the FLs and B-LBLs did not develop in parallel from early t(14;18)-positive IG-unmutated precursors, but that the B-LBLs developed from preexistent FL subclones that accumulated additional genetic damage. Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  19. Development of a sandwich ELISA for the thrombin light chain identified by serum proteome analysis

    Directory of Open Access Journals (Sweden)

    Kazuyuki Sogawa

    2017-08-01

    Full Text Available We previously identified novel biomarker candidates in biliary tract cancer (BTC using serum proteome analysis. Among several candidates, we focused on thrombin light chain which is a 4204 Da peptide as the most promising biomarker for BTC. To move thrombin light chain toward potential diagnostic use, we developed an enzyme immunoassay that enables to measure serum thrombin light chain levels.Both one monoclonal antibody specific to the N-termini and one polyclonal antibody were used to develop a sandwich ELISA for thrombin light chain. The assay was evaluated by comparing the results with those obtained by the ClinProt™ system. Serum samples were obtained from 20 patients with BTC, 20 patients with BBTDs and 20 HVs using the ClinProt™ system and ELISA.The results of the established ELISA showed a positive correlation with the findings by ClinProt™ system (slope=0.3386, intercept=34.901, r2=0.9641. The performance of the ELISA was satisfactory in terms of recovery (97.9–102.5% and within-run (1.5–4.8% and between-day (1.9–6.7% reproducibility. Serum thrombin light chain levels were significantly greater in BTC (176.5±47.2 ng/mL than in BBTDs (128.6±17.4 ng/mL and HVs (127.6±16.0 ng/mL (p<0.001.The sandwich ELISA developed in this study will be useful for validation of the diagnostic significance of serum thrombin light chain levels in various cancers. Keywords: Thrombin light chain, Biliary tract cancer, Sandwich ELISA, Serum biomarker

  20. Higher Serum Levels of Free ĸ plus λ Immunoglobulin Light Chains Ameliorate Survival of Hemodialysis Patients

    DEFF Research Database (Denmark)

    Thilo, Florian; Caspari, Christina; Scholze, Alexandra

    2011-01-01

    Background/Aims: Impaired immune function is common in patients with chronic renal failure. Now, we determined whether serum levels of free immunoglobulin light chains predict mortality in patients with chronic kidney disease stage 5 on hemodialysis. Methods: We performed a prospective cohort study...... of 160 hemodialysis patients with a median follow-up of 15 months (interquartile range, 3-44 months). Serum levels of free κ and λ immunoglobulin light chains were measured at the start of the study. The primary end point was mortality from any cause. Results: In survivors, median serum levels of free κ...... plus λ immunoglobulin light chains were significantly higher compared with nonsurvivors (p light chains above the median compared with patients with serum levels below the median of 210 mg...

  1. Implementation of supply chain management in supplier performance assessment using Analytical Hierarchy Process (AHP Objective Matrix (OMAX and Traffic Light System

    Directory of Open Access Journals (Sweden)

    Sukendar Irwan

    2018-01-01

    Full Text Available This study focuses on researching the implementation of supply chain management in supplier performance measurement using Analytical Hierarchy Process (AHP Objective Matrix (OMAX and Traffic Light System. The method used consisted of several stages: Identification stage of criteria variable and subcriteria variable, designing hierarchy AHP structure, calculating the weight of each criterion and subcriteria, supplier performance appraisal using OMAX method, calculating the total value of each supplier perfomance and identifying the performance of each supplier Using color indicator from Traffic Light System. Based on the results of the research, it can be seen that 9 out of 10 suppliers that are considered have a good performance while 1 supplier has a performance under the target.

  2. Comparing domain interactions within antibody Fabs with kappa and lambda light chains.

    Science.gov (United States)

    Toughiri, Raheleh; Wu, Xiufeng; Ruiz, Diana; Huang, Flora; Crissman, John W; Dickey, Mark; Froning, Karen; Conner, Elaine M; Cujec, Thomas P; Demarest, Stephen J

    2016-10-01

    IgG antibodies are multi-domain proteins with complex inter-domain interactions. Human IgG heavy chains (HCs) associate with light chains (LCs) of the κ or λ isotype to form mature antibodies capable of binding antigen. The HC/LC interaction involves 4 domains: VH and CH1 from the HC and VL and CL from the LC. Human Fabs with κ LCs have been well characterized for their unfolding behaviors and demonstrate a significant level of cooperativity and stabilization when all 4 domains are intact. Very little is known regarding the thermodynamic properties of human Fabs with λ LCs. Here, we dissect the domain contributions to Fab stability for both κ and λ LC-containing Fabs. We find the cooperativity of unfolding between the constant domains, CH1/Cλ, and variable domains, VH/Vλ, within λ LC-containing Fabs is significantly weaker than that of κ LC-containing Fabs. The data suggests there may not be an evolutionary necessity for strong variable/constant domain cooperativity within λ LC-containing Fabs. After investigating the biophysical properties of Fabs with mismatched variable and constant domain subunits (e.g., VH/Vκ paired with CH1/Cλ or T cell receptor Cα/Cβ), the major role of the constant domains for both κ- and λ-containing Fabs may be to reduce the hydrophobic exposure at the VH/VL interface. Even though Fabs with these non-native pairings were thermodynamically less stable, they secreted well from mammalian cells as well behaved monodisperse proteins, which was in contrast to what was observed with the VH/Vκ and VH/Vλ scFvs that secreted as a mixture of monomer and aggregates.

  3. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease.

    Science.gov (United States)

    Priyamvada, P S; Morkhandikar, S; Srinivas, B H; Parameswaran, S

    2015-01-01

    Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig) light chains. In heavy chain amyloidosis (AH), deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL), the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda) AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  4. Rapid analysis of rearranged kappa light chain genes of circulating polysaccharide-specific B lymphocytes by means of immunomagnetic beads and the polymerase chain reaction

    DEFF Research Database (Denmark)

    Hougs, L; Barington, T; Madsen, HO

    1993-01-01

    reaction (PCR) using in addition a degenerate kappa light chain signal peptide region primer. The PCR product was cloned into the M13mp18 phage. The cloning efficiency was 100-600 clones/ml of blood. Of the 86 clones sequenced, 90% represented rearranged kappa light chain genes from different antibody...... of the B lymphocytes activated in vivo. Here, we present a method for rapid analysis of the rearranged kappa light chain genes used by human circulating antigen-specific B lymphocytes. After vaccination with Haemophilus influenzae type b capsular polysaccharide (HibCP) conjugated with protein, the Hib...

  5. Super-light and pearl-chain technology for support of ancient structures

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl; Schmidt, Jacob Wittrup; Goltermann, Per

    2014-01-01

    optimal and often curved paths of strong concrete assembled from smaller segments by prestressing wires, so that expensive curved moulds and supports can be avoided. Pearl-chains can provide a resistance to impact and earthquake of ancient structures. High-strength concrete and prestressed carbon fibre......The patented super-light technology is inspired by ancient Roman concrete structures with strong concrete placed, where the engineer would like the forces to be, and light concrete fills out the shape stabilizing the strong and protecting it. Pearl-chain technology is invented in order to create...... reinforcement may be applied, because the new technology solves the main problems for that, since the light aggregate concrete provides a fire protection needed for both materials and provides a stabilization of the slender cores in compression. The paper explains more about the new technology...

  6. Constant region of a kappa III immunoglobulin light chain as a major AL-amyloid protein

    DEFF Research Database (Denmark)

    Engvig, J P; Olsen, K E; Gislefoss, R E

    1998-01-01

    AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein and the correspond......AL-amyloidoses are generally described as a group of disorders in which N-terminal fragments of monoclonal immunoglobulin light chains are transferred into amyloid fibrils. We have, by amino acid sequence analyses and immunological methods, characterized the Bence-Jones protein...... and the corresponding AL protein as a kappa III immunoglobulin light chain from material of a patient with systemic AL-amyloidosis presenting as a local inguinal tumour. The two proteins showed some unique features. The major part of the AL amyloid fibril protein consisted of C-terminal fragments of the Bence......-Jones protein. Furthermore, both the Bence-Jones protein and the AL protein were glycosylated, with possibly a glycosylation in the constant part of the light chain....

  7. Heavy and Light chain amyloidosois presenting as complete heart block: A rare presentation of a rare disease

    Directory of Open Access Journals (Sweden)

    P S Priyamvada

    2015-01-01

    Full Text Available Amyloidosis is an uncommon disease characterized by deposition of proteinaceous material in the extracellular matrix, which results from abnormal protein folding. Even though more than 25 precursor proteins are identified, majority of systemic amyloidosis results from deposition of abnormal immunoglobulin (Ig light chains. In heavy chain amyloidosis (AH, deposits are derived from both heavy chain alone, whereas in heavy and light chain amyloidosis (AHL, the deposits are derived from Ig heavy chains and light chains. Both AH and AHL are extremely rare diseases. Here, we report an unusual presentation of IgG (lambda AHL amyloidosis in the background of multiple myeloma, where the initial clinical presentation was complete heart block, which preceded the definitive diagnosis by 18 months.

  8. Variable context Markov chains for HIV protease cleavage site prediction.

    Science.gov (United States)

    Oğul, Hasan

    2009-06-01

    Deciphering the knowledge of HIV protease specificity and developing computational tools for detecting its cleavage sites in protein polypeptide chain are very desirable for designing efficient and specific chemical inhibitors to prevent acquired immunodeficiency syndrome. In this study, we developed a generative model based on a generalization of variable order Markov chains (VOMC) for peptide sequences and adapted the model for prediction of their cleavability by certain proteases. The new method, called variable context Markov chains (VCMC), attempts to identify the context equivalence based on the evolutionary similarities between individual amino acids. It was applied for HIV-1 protease cleavage site prediction problem and shown to outperform existing methods in terms of prediction accuracy on a common dataset. In general, the method is a promising tool for prediction of cleavage sites of all proteases and encouraged to be used for any kind of peptide classification problem as well.

  9. Production of a phage-displayed single chain variable fragment ...

    African Journals Online (AJOL)

    Abstract. Purpose: To develop specific single chain variable fragments (scFv) against ... libraries. The binding ability of the selected scFv antibody fragments against the IBDV particles was ..... Hermelink H, Koscielniak E. A human recombinant.

  10. Isolated Light Chain Amyloidosis Involving the Parotid Gland: A Case Report.

    Science.gov (United States)

    Gareb, Barzi; Perry, Michael; Tadrous, Paul Joseph

    2018-03-08

    Amyloidosis in the parotid gland is rare and is usually associated with systemic amyloidosis. Localized amyloidosis in the parotid gland is extremely rare. We present a case of localized light chain amyloidosis of the parotid gland without systemic involvement. A 70-year-old woman presented with an asymptomatic swelling of the right parotid region. The findings of a physical examination, hematologic and biochemical investigations, imaging, and cytology were inconclusive. The patient underwent an extracapsular dissection of the right parotid gland. Histologic analysis showed that the tissue of the right parotid gland mostly consisted of amyloid deposition. The amyloid stained with antibodies to lambda light chains. Additional investigations showed no systemic involvement. The patient is asymptomatic 5 months after surgery. Clinicians should be aware of the possibility of localized amyloid light chain amyloidosis in the parotid gland, especially if magnetic resonance imaging, computed tomography imaging, and ultrasound findings are inconclusive, and they should recognize, evaluate, and treat it accordingly. Copyright © 2018 American Association of Oral and Maxillofacial Surgeons. All rights reserved.

  11. Falling chains as variable-mass systems: theoretical model and experimental analysis

    International Nuclear Information System (INIS)

    De Sousa, Célia A; Costa, Pedro; Gordo, Paulo M

    2012-01-01

    In this paper, we revisit, theoretically and experimentally, the fall of a folded U-chain and of a pile-chain. The model calculation implies the division of the whole system into two subsystems of variable mass, allowing us to explore the role of tensional contact forces at the boundary of the subsystems. This justifies, for instance, that the folded U-chain falls faster than the acceleration due to the gravitational force. This result, which matches quite well with the experimental data independently of the type of chain, implies that the falling chain is well described by energy conservation. We verify that these conclusions are not observed for the pile-chain motion. (paper)

  12. Early Prognostic Value of Monitoring Serum Free Light Chain in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation.

    Science.gov (United States)

    Özkurt, Zübeyde Nur; Sucak, Gülsan Türköz; Akı, Şahika Zeynep; Yağcı, Münci; Haznedar, Rauf

    2017-03-16

    We hypothesized the levels of free light chains obtained before and after autologous stem cell transplantation can be useful in predicting transplantation outcome. We analyzed 70 multiple myeloma patients. Abnormal free light chain ratios before stem cell transplantation were found to be associated early progression, although without any impact on overall survival. At day +30, the normalization of levels of involved free light chain related with early progression. According to these results almost one-third reduction of free light chain levels can predict favorable prognosis after autologous stem cell transplantation.

  13. Plasmonic nanoparticle chain in a light field: a resonant optical sail.

    Science.gov (United States)

    Albaladejo, Silvia; Sáenz, Juan José; Marqués, Manuel I

    2011-11-09

    Optical trapping and driving of small objects has become a topic of increasing interest in multidisciplinary sciences. We propose to use a chain made of metallic nanoparticles as a resonant light sail, attached by one end point to a transparent object and propelling it by the use of electromagnetic radiation. Driving forces exerted on the chain are theoretically studied as a function of radiation's wavelength and chain's alignments with respect to the direction of radiation. Interestingly, there is a window in the frequency spectrum in which null-torque equilibrium configuration, with minimum geometric cross section, corresponds to a maximum in the driving force.

  14. Multiwavelength light curve parameters of Cepheid variables

    Directory of Open Access Journals (Sweden)

    Bhardwaj Anupam

    2017-01-01

    Full Text Available We present a comparative analysis of theoretical and observed light curves of Cepheid variables using Fourier decomposition. The theoretical light curves at multiple wavelengths are generated using stellar pulsation models for chemical compositions representative of Cepheids in the Galaxy and Magellanic Clouds. The observed light curves at optical (VI, near-infrared (JHKs and mid-infrared (3.6 & 4.5-μm bands are compiled from the literature. We discuss the variation of light curve parameters as a function of period, wavelength and metallicity. Theoretical and observed Fourier amplitude parameters decrease with increase in wavelength while the phase parameters increase with wavelength. We find that theoretical amplitude parameters obtained using canonical mass-luminosity levels exhibit a greater offset with respect to observations when compared to non-canonical relations. We also discuss the impact of variation in convective efficiency on the light curve structure of Cepheid variables. The increase in mixing length parameter results in a zero-point offset in bolometric mean magnitudes and reduces the systematic large difference in theoretical amplitudes with respect to observations.

  15. Production of a phage-displayed single chain variable fragment ...

    African Journals Online (AJOL)

    Purpose: To develop specific single chain variable fragments (scFv) against infectious bursal disease virus (IBDV) via phage display technology. Methods: Purified viruses were initially applied for iterative panning rounds of scFv phage display libraries. The binding ability of the selected scFv antibody fragments against the ...

  16. Structural effects of a light emitting copolymer having perylene moieties in the side chain on the electroluminescent characteristics

    International Nuclear Information System (INIS)

    Lee, Chang Ho; Ryu, Seung Hoon; Jang, Hee Dong; Oh, Se Young

    2004-01-01

    We have synthesized a novel side chain light emitting copolymer. The side chain light emitting copolymer has a perylene moiety as an emitting unit and methylmethacrylate (MMA) as a spacer to decrease the concentration quenching of light emitting site in the polymer intrachain. These polymers are very soluble in most organic solvents such as monochlorobenzene, tetrahydrofuran, chloroform and benzene. The single-layered electroluminescent (EL) device consisting of ITO/carrier transporting copolymer and light emitting copolymer/Al was manufactured. The carrier transporting copolymer has triphenylamine moiety as a hole transporting unit and triazine moiety as an electron transporting unit in the polymer side chain. This device exhibits maximum external quantum efficiency when the MMA contents of light emitting copolymer is 30 wt.%. In particular, the device emits more blue light as MMA contents increase

  17. Determination of allergen specificity by heavy chains in grass pollen allergen-specific IgE antibodies.

    Science.gov (United States)

    Gadermaier, Elisabeth; Flicker, Sabine; Lupinek, Christian; Steinberger, Peter; Valenta, Rudolf

    2013-04-01

    Affinity and clonality of allergen-specific IgE antibodies are important determinants for the magnitude of IgE-mediated allergic inflammation. We sought to analyze the contribution of heavy and light chains of human allergen-specific IgE antibodies for allergen specificity and to test whether promiscuous pairing of heavy and light chains with different allergen specificity allows binding and might affect affinity. Ten IgE Fabs specific for 3 non-cross-reactive major timothy grass pollen allergens (Phl p 1, Phl p 2, and Phl p 5) obtained by means of combinatorial cloning from patients with grass pollen allergy were used to construct stable recombinant single chain variable fragments (ScFvs) representing the original Fabs and shuffled ScFvs in which heavy chains were recombined with light chains from IgE Fabs with specificity for other allergens by using the pCANTAB 5 E expression system. Possible ancestor genes for the heavy chain and light chain variable region-encoding genes were determined by using sequence comparison with the ImMunoGeneTics database, and their chromosomal locations were determined. Recombinant ScFvs were tested for allergen specificity and epitope recognition by means of direct and sandwich ELISA, and affinity by using surface plasmon resonance experiments. The shuffling experiments demonstrate that promiscuous pairing of heavy and light chains is possible and maintains allergen specificity, which is mainly determined by the heavy chains. ScFvs consisting of different heavy and light chains exhibited different affinities and even epitope specificity for the corresponding allergen. Our results indicate that allergen specificity of allergen-specific IgE is mainly determined by the heavy chains. Different heavy and light chain pairings in allergen-specific IgE antibodies affect affinity and epitope specificity and thus might influence clinical reactivity to allergens. Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by

  18. Development of anti-bovine IgA single chain variable fragment and its application in diagnosis of foot-and-mouth disease

    Science.gov (United States)

    Sridevi, N. V.; Shukra, A. M.; Neelakantam, B.; Anilkumar, J.; Madhanmohan, M.; Rajan, S.; Dev Chandran

    2014-01-01

    Recombinant antibody fragments like single chain variable fragments (scFvs) represent an attractive yet powerful alternative to immunoglobulins and hold great potential in the development of clinical diagnostic/therapeutic reagents. Structurally, scFvs are the smallest antibody fragments capable of retaining the antigen-binding capacity of whole antibodies and are composed of an immunoglobulin (Ig) variable light (VL) and variable heavy (VH) chain joined by a flexible polypeptide linker. In the present study, we constructed a scFv against bovine IgA from a hybridoma cell line IL-A71 that secretes a monoclonal antibody against bovine IgA using recombinant DNA technology. The scFv was expressed in Escherichia coli and purified using immobilized metal affinity chromatography (IMAC). The binding activity and specificity of the scFv was established by its non-reactivity toward other classes of immunoglobulins as determined by enzyme-linked immunosorbent assay (ELISA) and immunoblot analysis. Kinetic measurement of the scFv indicated that the recombinant antibody fragment had an affinity in picomolar range toward purified IgA. Furthermore, the scFv was used to develop a sensitive ELISA for the detection of foot and mouth disease virus (FMDV) carrier animals. PMID:24678404

  19. Phenotyping polyclonal kappa and lambda light chain molecular mass distributions in patient serum using mass spectrometry.

    Science.gov (United States)

    Barnidge, David R; Dasari, Surendra; Ramirez-Alvarado, Marina; Fontan, Adrian; Willrich, Maria A V; Tschumper, Renee C; Jelinek, Diane F; Snyder, Melissa R; Dispenzieri, Angela; Katzmann, Jerry A; Murray, David L

    2014-11-07

    We previously described a microLC-ESI-Q-TOF MS method for identifying monoclonal immunoglobulins in serum and then tracking them over time using their accurate molecular mass. Here we demonstrate how the same methodology can be used to identify and characterize polyclonal immunoglobulins in serum. We establish that two molecular mass distributions observed by microLC-ESI-Q-TOF MS are from polyclonal kappa and lambda light chains using a combination of theoretical molecular masses from gene sequence data and the analysis of commercially available purified polyclonal IgG kappa and IgG lambda from normal human serum. A linear regression comparison of kappa/lambda ratios for 74 serum samples (25 hypergammaglobulinemia, 24 hypogammaglobulinemia, 25 normal) determined by microflowLC-ESI-Q-TOF MS and immunonephelometry had a slope of 1.37 and a correlation coefficient of 0.639. In addition to providing kappa/lambda ratios, the same microLC-ESI-Q-TOF MS analysis can determine the molecular mass for oligoclonal light chains observed above the polyclonal background in patient samples. In 2 patients with immune disorders and hypergammaglobulinemia, we observed a skewed polyclonal molecular mass distribution which translated into biased kappa/lambda ratios. Mass spectrometry provides a rapid and simple way to combine the polyclonal kappa/lambda light chain abundance ratios with the identification of dominant monoclonal as well as oligoclonal light chain immunoglobulins. We anticipate that this approach to evaluating immunoglobulin light chains will lead to improved understanding of immune deficiencies, autoimmune diseases, and antibody responses.

  20. A prospective study of nutritional status in immunoglobulin light chain amyloidosis

    DEFF Research Database (Denmark)

    Sattianayagam, PT; Lane, T; Fox, Z

    2013-01-01

    Weight loss is common in systemic immunoglobulin light chain amyloidosis but there are limited data on the impact of nutritional status on outcome. Using the Patient-Generated Subjective Global Assessment (PG-SGA) score, we prospectively examined nutritional status in 110 consecutive newly-diagno...

  1. Localized Gastric Amyloidosis with Kappa and Lambda Light Chain Co-Expression

    Directory of Open Access Journals (Sweden)

    Yong Hwan Ahn

    2018-05-01

    Full Text Available Esophagogastroduodenoscopy for cancer screening was performed in a 55-year-old woman as part of a health screening program, and revealed a depressed lesion approximately 20 mm in diameter in the lesser curvature of the mid-gastric body. Several biopsy specimens were collected as the lesion resembled early gastric cancer; however, histopathologic evaluation revealed chronic active gastritis with an ulcer and amorphous eosinophilic material deposition. Congo red staining identified amyloid proteins, and apple-green birefringence was shown using polarized light microscopy. Immunohistochemical staining revealed the presence of kappa and lambda chain-positive plasma cells. There was no evidence of underlying plasma cell dyscrasia or amyloid deposition in other segments of the gastrointestinal tract. Echocardiography and computed tomography of the chest, abdomen, and pelvis did not show any significant findings. Thus, the patient was diagnosed with localized gastric amyloidosis with kappa and lambda light chain coexpression.

  2. A novel variable antibody fragment dimerized by leucine zippers with enhanced neutralizing potency against rabies virus G protein compared to its corresponding single-chain variable antibody fragment.

    Science.gov (United States)

    Li, Zhuang; Cheng, Yue; Xi, Hualong; Gu, Tiejun; Yuan, Ruosen; Chen, Xiaoxu; Jiang, Chunlai; Kong, Wei; Wu, Yongge

    2015-12-01

    Fatal rabies can be prevented effectively by post-exposure prophylactic (PEP) with rabies immunoglobulin (RIG). Single-chain variable fragments (scFv), which are composed of a variable heavy chain (VH) and a variable light chain (VL) connected by a peptide linker, can potentially be used to replace RIG. However, in our previous study, a scFv (scFV57S) specific for the rabies virus (RV) G protein showed a lower neutralizing potency than that of its parent IgG due to lower stability and altered peptide assembly pattern. In monoclonal antibodies, the VH and VL interact non-covalently, while in scFvs the VH is connected covalently with the VL by the artificial linker. In this study, we constructed and expressed two peptides 57VL-JUN-HIS and 57VH-FOS-HA in Escherichia coli. The well-known Fos and Jun leucine zippers were utilized to dimerize VH and VL similarly to the IgG counterpart. The two peptides assembled to form zipFv57S in vitro. Due to the greater similarity in structure with IgG, the zipFv57S protein showed a higher binding ability and affinity resulting in notable improvement of in vitro neutralizing activity over its corresponding scFv. The zipFv57S protein was also found to be more stable and showed similar protective rate as RIG in mice challenged with a lethal dose of RV. Our results not only indicated zipFv57S as an ideal alternative for RIG in PEP but also offered a novel and efficient hetero-dimerization pattern of VH and VL leading to enhanced neutralizing potency. Copyright © 2015. Published by Elsevier Ltd.

  3. An investigation into UV light exposure as an experimental model for artificial aging on tensile strength and force delivery of elastomeric chain.

    Science.gov (United States)

    Wahab, Siti Waznah; Bister, Dirk; Sherriff, Martyn

    2014-02-01

    This study investigated the effect of ultraviolet type A light (UVA) exposure on the tensile properties of elastomeric chain. UVA light exposure was used as model for artificial aging, simulating prolonged storage of elastomeric chain. Tensile strength (n = 60) was measured after exposing Ormco, Forestadent and 3M chains to UVA light for 0, 2, 3, and 4 weeks. Force decay was measured (n = 60) using chain exposed for 5, 10, and 14 days. The chains were subsequently stretched at a constant distance and the resulting forces measured at 0, 1, 24 hours and 7, 14, 21, and 28 days. This test simulated a clinical scenario of pre-stretching and subsequent shortening of elastomeric chain. Tensile strength had statistically significant difference and was directly related to the duration of ultraviolet (UV) light exposure. Forestadent chain, which had the second highest value for the 'as received' product, showed the most consistent values over time with the lowest degradation. Ormco showed the lowest values for 'as received' as well as after UV exposure; 3M chain had the highest loss of tensile strength. Force decay was also significantly different. UV light exposure of 10 days or more appears to mark a 'watershed' between products: 3M had most survivors, Forestadent chain had some survivors, depending on the time the chain was stretched for. None of the Ormco product survived UV light exposure for more than 5 days. UVA light exposure may be used as a model for artificial aging as it reduces force delivery and tensile strength of exposed chains.

  4. Anxiety and depression among amyloid light-chain cardiac amyloidosis patients: The role of life satisfaction.

    Science.gov (United States)

    Smorti, Martina; Guarnieri, Silvia; Bergesio, Franco; Perfetto, Federico; Cappelli, Francesco

    2016-06-01

    The present study aimed to provide a contribution to the study of a rare disease, amyloid light-chain (AL) cardiac amyloidosis, which is the most common type of systemic amyloidosis. In AL amyloidosis prognosis is determined by cardiac involvement. Although the association between psychological distress (e.g. anxiety and depression) and AL cardiac amyloidosis is documented, very little is known about the psychosocial variables that may mediate the association. The aim of the study is therefore to examine the potential mediating role of life satisfaction in the relationship between cardiac symptom severity (independent variable) and anxious and depressive symptoms (dependent variables) in AL patients. Forty-three AL amyloidosis patients (57.1% males) with cardiac amyloidosis were administered the Satisfaction with Life Scale, the State-Trait Anxiety Inventory and the Centre for Epidemiological Study-Depression Scale. Clinical variables such as months since cardiac symptom onset and cardiac symptom severity were collected. Findings showed significant relationships between symptom severity and psychological disorders (e.g. anxiety and depression) and these were mediated by life satisfaction. Overall, findings highlight the importance of subjective well-being (e.g. life satisfaction) to reduce anxious and depressive symptoms and to improve general health in AL patients. © The European Society of Cardiology 2015.

  5. Baxter Q-operator and separation of variables for the open SL(2, R) spin chain

    International Nuclear Information System (INIS)

    Derkachov, Sergey E.; Korchemsky, Gregory P.; Manashov, Alexander N.

    2003-01-01

    We construct the Baxter Q-operator and the representation of the Separated Variables (SoV) for the homogeneous open SL(2, R) spin chain. Applying the diagrammatical approach, we calculate Sklyanin's integration measure in the separated variables and obtain the solution to the spectral problem for the model in terms of the eigenvalues of the Q-operator. We show that the transition kernel to the SoV representation is factorized into the product of certain operators each depending on a single separated variable. As a consequence, it has a universal pyramid-like form that has been already observed for vari- ous quantum integrable models such as periodic Toda chain, closed SL(2, R) and SL(2, C) spin chains. (author)

  6. Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T

    1989-01-01

    The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated...

  7. Observation of the dynamics of magnetically induced chains of sub-micron superparamagnetic beads in aqueous solutions by laser light scattering

    International Nuclear Information System (INIS)

    Tanizawa, Y; Tashiro, T; Sandhu, A; Ko, P J

    2013-01-01

    Optical monitoring the behaviour of magnetically induced self-assembled chains of superparamagnetic beads (SPBs) are of interest for biomedical applications such as biosensors. However, it is difficult to directly monitor magnetically induced self-assembly of sub-micron nano-beads with conventional optical microscopes. Here, we describe the optical observation of the dynamics of magnetically induced self-assembled rotating chains of 130 nm SPBs in aqueous solutions by laser light scattering. Magnetic fields of ∼1 kOe were applied to control the self-assembly chains of SPBs and their behaviour analyzed by monitoring the intensity of laser light scattered from the chain structures. We compared the light scattering from chains that were formed only by the application of external fields with chains formed by beads functionalized by EDC, where chemical reactions lead to the bonding of individual beads to form chains. The EDC experiments are a precursor to experiments on molecular recognition applications for biomedical diagnostics.

  8. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis.

    Science.gov (United States)

    Bever, Katherine M; Masha, Luke I; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L; Sanchorawala, Vaishali; Seldin, David C; Sloan, J Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60-11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. Copyright© Ferrata Storti Foundation.

  9. Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

    Science.gov (United States)

    Bever, Katherine M.; Masha, Luke I.; Sun, Fangui; Stern, Lauren; Havasi, Andrea; Berk, John L.; Sanchorawala, Vaishali; Seldin, David C.; Sloan, J. Mark

    2016-01-01

    Patients with immunoglobulin light chain amyloidosis are at risk for both thrombotic and bleeding complications. While the hemostatic defects have been extensively studied, less is known about thrombotic complications in this disease. This retrospective study examined the frequency of venous thromboembolism in 929 patients with immunoglobulin light chain amyloidosis presenting to a single referral center, correlated risk of venous thromboembolism with clinical and laboratory factors, and examined complications of anticoagulation in this population. Sixty-five patients (7%) were documented as having at least one venous thromboembolic event. Eighty percent of these patients had events within one year prior to or following diagnosis. Lower serum albumin was associated with increased risk of VTE, with a hazard ratio of 4.30 (CI 1.60–11.55; P=0.0038) for serum albumin less than 3 g/dL compared to serum albumin greater than 4 g/dL. Severe bleeding complications were observed in 5 out of 57 patients with venous thromboembolism undergoing treatment with anticoagulation. Prospective investigation should be undertaken to better risk stratify these patients and to determine the optimal strategies for prophylaxis against and management of venous thromboembolism. PMID:26452981

  10. Association of immunoglobulin G4 and free light chain with idiopathic pleural effusion.

    Science.gov (United States)

    Murata, Y; Aoe, K; Mimura-Kimura, Y; Murakami, T; Oishi, K; Matsumoto, T; Ueoka, H; Matsunaga, K; Yano, M; Mimura, Y

    2017-10-01

    The cause of pleural effusion remains uncertain in approximately 15% of patients despite exhaustive evaluation. As recently described immunoglobulin (Ig)G4-related disease is a fibroinflammatory disorder that can affect various organs, including the lungs, we investigate whether idiopathic pleural effusion includes IgG4-associated etiology. Between 2000 and 2012, we collected 830 pleural fluid samples and reviewed 35 patients with pleural effusions undiagnosed after pleural biopsy at Yamaguchi-Ube Medical Center. Importantly, IgG4 immunostaining revealed infiltration of IgG4-positive plasma cells in the pleura of 12 patients (34%, IgG4 + group). The median effusion IgG4 level was 41 mg/dl in the IgG4 + group and 27 mg/dl in the IgG4 - group (P effusion IgG4 antibodies of patients in the IgG4 + group were heterogeneous by two-dimensional electrophoresis, indicating the absence of clonality of the IgG4 antibodies. Interestingly, the κ light chains were more heterogeneous than the λ light chains. The measurement of the κ and λ free light chain (FLC) levels in the pleural fluids showed significantly different κ FLC levels (median: 28·0 versus 9·1 mg/dl, P pleural effusions and provide insights into the diagnosis, pathogenesis and therapeutic opportunities of IgG4-associated pleural effusion. © 2017 British Society for Immunology.

  11. Subset of Kappa and Lambda Germline Sequences Result in Light Chains with a Higher Molecular Mass Phenotype.

    Science.gov (United States)

    Barnidge, David R; Lundström, Susanna L; Zhang, Bo; Dasari, Surendra; Murray, David L; Zubarev, Roman A

    2015-12-04

    In our previous work, we showed that electrospray ionization of intact polyclonal kappa and lambda light chains isolated from normal serum generates two distinct, Gaussian-shaped, molecular mass distributions representing the light-chain repertoire. During the analysis of a large (>100) patient sample set, we noticed a low-intensity molecular mass distribution with a mean of approximately 24 250 Da, roughly 800 Da higher than the mean of the typical kappa molecular-mass distribution mean of 23 450 Da. We also observed distinct clones in this region that did not appear to contain any typical post-translational modifications that would account for such a large mass shift. To determine the origin of the high molecular mass clones, we performed de novo bottom-up mass spectrometry on a purified IgM monoclonal light chain that had a calculated molecular mass of 24 275.03 Da. The entire sequence of the monoclonal light chain was determined using multienzyme digestion and de novo sequence-alignment software and was found to belong to the germline allele IGKV2-30. The alignment of kappa germline sequences revealed ten IGKV2 and one IGKV4 sequences that contained additional amino acids in their CDR1 region, creating the high-molecular-mass phenotype. We also performed an alignment of lambda germline sequences, which showed additional amino acids in the CDR2 region, and the FR3 region of functional germline sequences that result in a high-molecular-mass phenotype. The work presented here illustrates the ability of mass spectrometry to provide information on the diversity of light-chain molecular mass phenotypes in circulation, which reflects the germline sequences selected by the immunoglobulin-secreting B-cell population.

  12. Light-induced circular birefringence in cyanoazobenzene side-chain liquid-crystalline polyester films

    DEFF Research Database (Denmark)

    Naydenova, I; Nikolova, L; Ramanujam, P.S.

    1999-01-01

    We report the inducement of large circular birefringence (optical activity) in films of a cyanoazobenzene side-chain liquid-crystalline polyester on illumination with circularly polarized light. The polyester has no chiral groups and is initially isotropic. The induced optical rotation is up to 5...

  13. Automated colorimetric in situ hybridization (CISH) detection of immunoglobulin (Ig) light chain mRNA expression in plasma cell (PC) dyscrasias and non-Hodgkin lymphoma.

    Science.gov (United States)

    Beck, Rose C; Tubbs, Raymond R; Hussein, Mohamad; Pettay, James; Hsi, Eric D

    2003-03-01

    Immunohistochemistry (IHC) is frequently used to detect plasma cell (PC) or B cell monoclonality in histologic sections, but its interpretation is often confounded by background staining. We evaluated a new automated method for colorimetric in situ hybridization (CISH) detection of clonality in PC dyscrasias and small B cell lymphomas. Cases of PC dyscrasia included multiple myeloma (MM; 31 cases), plasmacytoma (seven cases), or amyloidosis (one case), while cases of lymphoma included small lymphocytic (three cases), marginal zone (four cases), lymphoplasmacytic (three cases), and mantle cell lymphomas (three cases). Tissue sections were stained for kappa and lambda light chains by IHC and for light chain mRNA by automated CISH using haptenated probes. Twenty-eight of 31 MM cases had detectable light chain restriction by IHC. Thirty of 31 MM cases demonstrated light chain restriction by CISH, including 2 cases with uninterpretable IHC and one case of nonsecretory myeloma, which was negative for light chains by IHC. Seven of 7 plasmacytoma cases had detectable light chain restriction by CISH, including one case of nonsecretory plasmacytoma in which IHC was noninformative. Automated CISH demonstrated monoclonality in 9 of 13 cases of B cell non-Hodgkin lymphoma and had a slightly higher sensitivity than IHC (6 of 13 cases), especially in cases of lymphoplasmacytic and marginal zone lymphoma. Overall, there were no discrepancies in light chain restriction results between IHC, CISH, or serum paraprotein analysis. Automated CISH is useful in detecting light chain expression in paraffin sections and appeared superior to IHC for light chain detection in PC dyscrasias and B cell non-Hodgkin lymphomas, predominantly due to lack of background staining.

  14. Characterization of Nighttime Light Variability Over the Southeastern United States

    Science.gov (United States)

    Cole, Tony A.; Molthan, Andrew L.; Schultz, Lori A.

    2016-01-01

    City lights provide indications of human activity at night. Nighttime satellite imagery offers daily snapshots of this activity. With calibrated, science-quality imagery, long-term monitoring can also be achieved. The degree to which city lights fluctuate, however, is not well known. For the application of detecting power outages, this degree of variability is crucial for assessing reductions to city lights based on historical trends. Eight southeastern U.S. cities are analyzed to understand the relationship between emission variability and several population centers. A preliminary, example case power outage study is also discussed as a transition into future work.

  15. In vitro aggregation behavior of a non-amyloidogenic λ light chain dimer deriving from U266 multiple myeloma cells.

    Directory of Open Access Journals (Sweden)

    Paolo Arosio

    Full Text Available Excessive production of monoclonal light chains due to multiple myeloma can induce aggregation-related disorders, such as light chain amyloidosis (AL and light chain deposition diseases (LCDD. In this work, we produce a non-amyloidogenic IgE λ light chain dimer from human mammalian cells U266, which originated from a patient suffering from multiple myeloma, and we investigate the effect of several physicochemical parameters on the in vitro stability of this protein. The dimer is stable in physiological conditions and aggregation is observed only when strong denaturating conditions are applied (acidic pH with salt at large concentration or heating at melting temperature T(m at pH 7.4. The produced aggregates are spherical, amorphous oligomers. Despite the larger β-sheet content of such oligomers with respect to the native state, they do not bind Congo Red or ThT. The impossibility to obtain fibrils from the light chain dimer suggests that the occurrence of amyloidosis in patients requires the presence of the light chain fragment in the monomer form, while dimer can form only amorphous oligomers or amorphous deposits. No aggregation is observed after denaturant addition at pH 7.4 or at pH 2.0 with low salt concentration, indicating that not a generic unfolding but specific conformational changes are necessary to trigger aggregation. A specific anion effect in increasing the aggregation rate at pH 2.0 is observed according to the following order: SO(4(-≫Cl(->H(2PO(4(-, confirming the peculiar role of sulfate in promoting protein aggregation. It is found that, at least for the investigated case, the mechanism of the sulfate effect is related to protein secondary structure changes induced by anion binding.

  16. Lambda light chain disease associated with myelomatous pericardial and pleural effusion

    International Nuclear Information System (INIS)

    Helbig, G.; Wieczorkiewicz, A.; Dziaczkowska-Suszek, J.; Krzemien, S.

    2009-01-01

    The paper presents the case of a 53-year patient with lambda light chain disease and concomitant myelomatous pleural and pericardial effusions. The symptoms of cardiac failure dominated the clinical manifestation. Only moderate plasma cell infiltration in bone marrow was present, whereas 100% of these cells infiltrated the pleura. Chemotherapy appeared to be ineffective and patient died from cardiac failure. (authors)

  17. Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy

    DEFF Research Database (Denmark)

    Toftmann Hansen, Charlotte; Pedersen, Per T.; Jensen, Bo Amdi

    Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy.......Value of the free light chain analysis in the clinical evaluation of response in multiple myeloma patients receiving anti-myeloma therapy....

  18. QUEST1 Variability Survey. III. Light Curve Catalog Update

    Science.gov (United States)

    Rengstorf, A. W.; Thompson, D. L.; Mufson, S. L.; Andrews, P.; Honeycutt, R. K.; Vivas, A. K.; Abad, C.; Adams, B.; Bailyn, C.; Baltay, C.; Bongiovanni, A.; Briceño, C.; Bruzual, G.; Coppi, P.; Della Prugna, F.; Emmet, W.; Ferrín, I.; Fuenmayor, F.; Gebhard, M.; Hernández, J.; Magris, G.; Musser, J.; Naranjo, O.; Oemler, A.; Rosenzweig, P.; Sabbey, C. N.; Sánchez, Ge.; Sánchez, Gu.; Schaefer, B.; Schenner, H.; Sinnott, J.; Snyder, J. A.; Sofia, S.; Stock, J.; van Altena, W.

    2009-03-01

    This paper reports an update to the QUEST1 (QUasar Equatorial Survey Team, Phase 1) Variability Survey (QVS) light curve catalog, which links QVS instrumental magnitude light curves to Sloan Digital Sky Survey (SDSS) objects and photometry. In the time since the original QVS catalog release, the overlap between publicly available SDSS data and QVS data has increased by 8% in sky coverage and 16,728 in number of matched objects. The astrometric matching and the treatment of SDSS masks have been refined for the updated catalog. We report on these improvements and present multiple bandpass light curves, global variability information, and matched SDSS photometry for 214,941 QUEST1 objects. Based on observations obtained at the Llano del Hato National Astronomical Observatory, operated by the Centro de Investigaciones de Astronomía for the Ministerio de Ciencia y Tecnologia of Venezuela.

  19. Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, Takashi; Izumi, Tohru; Shibata, Akira (Niigata Univ. (Japan). School of Medicine)

    1992-08-01

    Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51[+-]11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of [sup 201]Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author).

  20. Clinical assessment of serum myosin light chain I in patients with dilated cardiomyopathy

    International Nuclear Information System (INIS)

    Tsuda, Takashi; Izumi, Tohru; Shibata, Akira

    1992-01-01

    Serum cardiac myosin light chain I (LCI) levels were quantitated using a radioimmunoassay kit in patients suspected of dilated cardiomyopathy (DCM). In this study, 55 patients were evaluated between 1986 and 1991. They were composed of 40 males and 15 females, and their age was 27-75 years (51±11 years). The patients with renal dysfunction were excluded due to their serum creatinine levels (>2.0 mg/dl). After cardiac catheterization, endomyocardial biopsy and echocardiography, 44 patients were diagnosed as DCM, 2 as ischemic heart disease, 2 as chronic myocarditis, 1 as restrictive cardiomyopathy, 1 as dilated hypertrophic cardiomyopathy, 1 as cardiac amyloidosis, 2 as myopathy, 1 as polymyositis and 1 as hypothyroidism. Only two patients with DCM had elevated LCI. Besides, two patients with myopathy or hypothyroidism had elevated LCI. In the follow-up, one patient died suddenly 6 months later and another showed normal value of LCI four years later. LCI elevation in DCM was not related to either the severity of heart failure or cardiac function and it showed no finding of 201 Tl myocardial defect or elevated CPK. The mechanism for elevated LCI in myopathy is related to a crossreaction with myosin light chain in the skeletal muscle. In hypothyroidism, it may be related to decreased clearance of normal LCI concentration or increased myosin light chain from damaged skeletal muscle. In conclusion, it is evident that the measurement of LCI is not helpful in clinical assessment of patients with DCM, but may be useful in detection of secondary cardiomyopathy. (author)

  1. Double phosphorylation of the myosin regulatory light chain during rigor mortis of bovine Longissimus muscle.

    Science.gov (United States)

    Muroya, Susumu; Ohnishi-Kameyama, Mayumi; Oe, Mika; Nakajima, Ikuyo; Shibata, Masahiro; Chikuni, Koichi

    2007-05-16

    To investigate changes in myosin light chains (MyLCs) during postmortem aging of the bovine longissimus muscle, we performed two-dimensional gel electrophoresis followed by identification with matrix-assisted laser desorption ionization time-of-flight mass spectrometry. The results of fluorescent differential gel electrophoresis showed that two spots of the myosin regulatory light chain (MyLC2) at pI values of 4.6 and 4.7 shifted toward those at pI values of 4.5 and 4.6, respectively, by 24 h postmortem when rigor mortis was completed. Meanwhile, the MyLC1 and MyLC3 spots did not change during the 14 days postmortem. Phosphoprotein-specific staining of the gels demonstrated that the MyLC2 proteins at pI values of 4.5 and 4.6 were phosphorylated. Furthermore, possible N-terminal region peptides containing one and two phosphoserine residues were detected in each mass spectrum of the MyLC2 spots at pI values of 4.5 and 4.6, respectively. These results demonstrated that MyLC2 became doubly phosphorylated during rigor formation of the bovine longissimus, suggesting involvement of the MyLC2 phosphorylation in the progress of beef rigor mortis. Bovine; myosin regulatory light chain (RLC, MyLC2); phosphorylation; rigor mortis; skeletal muscle.

  2. EXPLORING THE VARIABLE SKY WITH LINEAR. III. CLASSIFICATION OF PERIODIC LIGHT CURVES

    Energy Technology Data Exchange (ETDEWEB)

    Palaversa, Lovro; Eyer, Laurent; Rimoldini, Lorenzo [Observatoire Astronomique de l' Université de Genève, 51 chemin des Maillettes, CH-1290 Sauverny (Switzerland); Ivezić, Željko; Loebman, Sarah; Hunt-Walker, Nicholas; VanderPlas, Jacob; Westman, David; Becker, Andrew C. [Department of Astronomy, University of Washington, P.O. Box 351580, Seattle, WA 98195-1580 (United States); Ruždjak, Domagoj; Sudar, Davor; Božić, Hrvoje [Hvar Observatory, Faculty of Geodesy, Kačićeva 26, 10000 Zagreb (Croatia); Galin, Mario [Faculty of Geodesy, Kačićeva 26, 10000 Zagreb (Croatia); Kroflin, Andrea; Mesarić, Martina; Munk, Petra; Vrbanec, Dijana [Department of Physics, Faculty of Science, University of Zagreb, Bijenička cesta 32, 10000 Zagreb (Croatia); Sesar, Branimir [Division of Physics, Mathematics, and Astronomy, Caltech, Pasadena, CA 91125 (United States); Stuart, J. Scott [Lincoln Laboratory, Massachusetts Institute of Technology, 244 Wood Street, Lexington, MA 02420-9108 (United States); Srdoč, Gregor, E-mail: lovro.palaversa@unige.ch [Saršoni 90, 51216 Viškovo (Croatia); and others

    2013-10-01

    We describe the construction of a highly reliable sample of ∼7000 optically faint periodic variable stars with light curves obtained by the asteroid survey LINEAR across 10,000 deg{sup 2} of the northern sky. The majority of these variables have not been cataloged yet. The sample flux limit is several magnitudes fainter than most other wide-angle surveys; the photometric errors range from ∼0.03 mag at r = 15 to ∼0.20 mag at r = 18. Light curves include on average 250 data points, collected over about a decade. Using Sloan Digital Sky Survey (SDSS) based photometric recalibration of the LINEAR data for about 25 million objects, we selected ∼200,000 most probable candidate variables with r < 17 and visually confirmed and classified ∼7000 periodic variables using phased light curves. The reliability and uniformity of visual classification across eight human classifiers was calibrated and tested using a catalog of variable stars from the SDSS Stripe 82 region and verified using an unsupervised machine learning approach. The resulting sample of periodic LINEAR variables is dominated by 3900 RR Lyrae stars and 2700 eclipsing binary stars of all subtypes and includes small fractions of relatively rare populations such as asymptotic giant branch stars and SX Phoenicis stars. We discuss the distribution of these mostly uncataloged variables in various diagrams constructed with optical-to-infrared SDSS, Two Micron All Sky Survey, and Wide-field Infrared Survey Explorer photometry, and with LINEAR light-curve features. We find that the combination of light-curve features and colors enables classification schemes much more powerful than when colors or light curves are each used separately. An interesting side result is a robust and precise quantitative description of a strong correlation between the light-curve period and color/spectral type for close and contact eclipsing binary stars (β Lyrae and W UMa): as the color-based spectral type varies from K4 to F5, the

  3. Biased immunoglobulin light chain gene usage in the shark1

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-01-01

    This study of a large family of kappa light (L) chain clusters in nurse shark completes the characterization of its classical immunoglobulin (Ig) gene content (two heavy chain classes, mu and omega, and four L chain isotopes, kappa, lambda, sigma, and sigma-2). The shark kappa clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over a ~500 bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ca. 39 kappa clusters are pre-rearranged in the germline (GL-joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, non-productive, and sterile transcripts of the kappa clusters compared to the other three L chain isotypes. Kappa cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and non-productive rearrangements. These results show that the individual activation of the spatially distant kappa clusters is non-random. Although both split and GL-joined kappa genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. PMID:26342033

  4. Molecular cloning and complete nucleotide sequence of a human ventricular myosin light chain 1

    Energy Technology Data Exchange (ETDEWEB)

    Hoffmann, E; Shi, Q W; Floroff, M; Mickle, D A.G.; Wu, T W; Olley, P M; Jackowski, G

    1988-03-25

    Human ventricular plasmid library was constructed. The library was screened with the oligonucleotide probe (17-mer) corresponding to a conserve region of myosin light chain 1 near the carboxy terminal. Full length cDNA recombinant plasmid containing 1100 bp insert was isolated. RNA blot hybridization with this insert detected a message of approximately 1500 bp corresponding to the size of VLCl and mRNA. Complete nucleotide sequence of the coding region was determined in M13 subclones using dideoxy chain termination method. With the isolation of this clone (pCD HLVCl), the publication of the complete nucleotide sequence of HVLCl and the predicted secondary structure of this protein will aid in understanding of the biochemistry of myosin and its function in contraction, the evolution of myosin light genes and the genetic, developmental and physiological regulation of myosin genes.

  5. Diagnostic reference range of κ/λ free light chain ratio to screen for Bence Jones proteinuria is not significantly influenced by GFR.

    Science.gov (United States)

    Schmidt-Hieltjes, Yvonne; Elshof, Clemens; Roovers, Lian; Ruinemans-Koerts, Janneke

    2016-05-01

    The aim of our study was to analyse whether the κ/λ free light chain ratio reference range for screening for Bence Jones proteinuria should be dependent on the estimated glomerular filtration rate (eGFR). The serum κ/λ free light chain ratio, eGFR, serum M-protein and Bence Jones protein were measured in 544 patients for whom Bence Jones protein analysis was ordered. In the population of patients without Bence Jones proteinuria or a M-protein (n = 402), there is no gradual increase in κ/λ free light chain ratio with diminishing eGFR. The κ/λ free light chain ratio in this group was 0.56-1.86 (95% interval). With this diagnostic reference range of the κ/λ ratio, 105 of the 110 patients with Bence Jones protein could be identified correctly. Only five patients with Bence Jones proteinuria (free light chain ratio was measured without the presence of Bence Jones proteinuria. A κ/λ free light chain ratio in serum can be used safely and efficiently to select urine samples which should be analysed for Bence Jones proteinuria with an electrophoresis/immunofixation technique. Using this diagnostic reference range, the number of urine samples which should be analysed by electrophoresis/immunofixation could be reduced by 74%. The diagnostic reference interval can be determined best in a group of patients for whom Bence Jones analysis is indicated. For calculation of this reference range, the eGFR value does not need to be taken into account. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. Suppression of Aggrus/podoplanin-induced platelet aggregation and pulmonary metastasis by a single-chain antibody variable region fragment

    International Nuclear Information System (INIS)

    Miyata, Kenichi; Takagi, Satoshi; Sato, Shigeo; Morioka, Hiroshi; Shiba, Kiyotaka; Minamisawa, Tamiko; Takami, Miho; Fujita, Naoya

    2014-01-01

    Almost all highly metastatic tumor cells possess high platelet aggregating abilities, thereby form large tumor cell-platelet aggregates in the microvasculature. Embolization of tumor cells in the microvasculature is considered to be the first step in metastasis to distant organs. We previously identified the platelet aggregation-inducing factor expressed on the surfaces of highly metastatic tumor cells and named as Aggrus. Aggrus was observed to be identical to the marker protein podoplanin (alternative names, T1α, OTS-8, and others). Aggrus is frequently overexpressed in several types of tumors and enhances platelet aggregation by interacting with the platelet receptor C-type lectin-like receptor 2 (CLEC-2). Here, we generated a novel single-chain antibody variable region fragment (scFv) by linking the variable regions of heavy and light chains of the neutralizing anti-human Aggrus monoclonal antibody MS-1 with a flexible peptide linker. Unfortunately, the generated KM10 scFv failed to suppress Aggrus-induced platelet aggregation in vitro. Therefore, we performed phage display screening and finally obtained a high-affinity scFv, K-11. K-11 scFv was able to suppress Aggrus-induced platelet aggregation in vitro. Moreover, K-11 scFv prevented the formation of pulmonary metastasis in vivo. These results suggest that K-11 scFv may be useful as metastasis inhibitory scFv and is expected to aid in the development of preclinical and clinical examinations of Aggrus-targeted cancer therapies

  7. Development of single chain variable fragment (scFv) antibodies against Xylella fastidiosa subsp. pauca by phage display.

    Science.gov (United States)

    Yuan, Qing; Jordan, Ramon; Brlansky, Ronald H; Istomina, Olga; Hartung, John

    2015-10-01

    Xylella fastidiosa is a member of the gamma proteobacteria. It is fastidious, insect-vectored and xylem-limited and causes a variety of diseases, some severe, on a wide range of economically important perennial crops, including grape and citrus. Antibody based detection assays are commercially available for X. fastidiosa, and are effective at the species, but not at the subspecies level. We have made a library of scFv antibody fragments directed against X. fastidiosa subsp. pauca strain 9a5c (citrus) by using phage display technology. Antibody gene repertoires were PCR-amplified using 23 primers for the heavy chain variable region (V(H)) and 21 primers for the light chain variable region (V(L)). The V(H) and V(L) were joined by overlap extension PCR, and then the genes of the scFv library were ligated into the phage vector pKM19. The library contained 1.2×10(7) independent clones with full-length scFv inserts. In each of 3cycles of affinity-selection with 9a5c, about 1.0×10(12) phage were used for panning with 4.1×10(6), 7.1×10(6), 2.1×10(7) phage recovered after the first, second and third cycles, respectively. Sixty-six percent of clones from the final library bound X. fastidiosa 9a5c in an ELISA. Some of these scFv antibodies recognized strain 9a5c and did not recognize X. fastidiosa strains that cause Pierce's disease of grapevine. Published by Elsevier B.V.

  8. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features.

    Science.gov (United States)

    Kumar, Shaji; Dispenzieri, Angela; Katzmann, Jerry A; Larson, Dirk R; Colby, Colin L; Lacy, Martha Q; Hayman, Suzanne R; Buadi, Francis K; Leung, Nelson; Zeldenrust, Steve R; Ramirez-Alvarado, Marina; Clark, Raynell J; Kyle, Robert A; Rajkumar, S Vincent; Gertz, Morie A

    2010-12-09

    Immunoglobulin free light chains (FLCs) are the precursors of amyloid fibrils in primary amyloidosis (AL). We studied the relationship between FLC levels and clinical features in 730 patients with newly diagnosed AL. The plasma cell clone was λ in 72% patients, and κ in 28% patients. κ-AL had more GI tract and liver involvement, where as renal involvement was more with λ-AL. While the overall survival (OS) was similar for κ and λ-AL, the median OS for those without an identifiable serum heavy chain was significantly shorter (12.6 vs 29.9 months; P = .02). The OS was shorter among those with a higher dFLC (involved FLC-uninvolved FLC; κ > 29.4 mg/dL or λ > 18.2 mg/dL using median for cutoff); 10.9 vs 37.1 months; P analysis, dFLC was independent of other prognostic factors. The type of light chain impacts the spectrum of organ involvement and the FLC burden correlates with survival in AL.

  9. Generation and characterisation of murine monoclonal antibodies specific for cervine immunoglobulin light chain, IgM and IgG

    International Nuclear Information System (INIS)

    Hibma, M.; Griffin, J.F.T.

    1992-01-01

    Monoclonal antibodies (mAb) which react with cervine immunoglobulin (Ig) light chain, IgM and IgG were produced using conventional cell fusion technology. Hybridoma supernatants were initially screened for specificity against cervine Ig using an enzyme-linked immunosorbent assay (ELISA). The specificity of supernatants against size-fractionated cervine Ig was further determined. Supernatants were characterised using western blotting and autoradiographic techniques. The mAb OU1G, OU2G and OU3G were specific for cervine gamma-chain of IgG, whereas OU1L was specific for light chain of Ig. A further mAb (OU1M) bound IgM and not IgG. These mAb were found to have varying cross-reactivity against Ig from other species

  10. Effect of including decay chains on predictions of equilibrium-type terrestrial food chain models

    International Nuclear Information System (INIS)

    Kirchner, G.

    1990-01-01

    Equilibrium-type food chain models are commonly used for assessing the radiological impact to man from environmental releases of radionuclides. Usually these do not take into account build-up of radioactive decay products during environmental transport. This may be a potential source of underprediction. For estimating consequences of this simplification, the equations of an internationally recognised terrestrial food chain model have been extended to include decay chains of variable length. Example calculations show that for releases from light water reactors as expected both during routine operation and in the case of severe accidents, the build-up of decay products during environmental transport is generally of minor importance. However, a considerable number of radionuclides of potential radiological significance have been identified which show marked contributions of decay products to calculated contamination of human food and resulting radiation dose rates. (author)

  11. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    Science.gov (United States)

    Ghiotto, Fabio; Marcatili, Paolo; Tenca, Claudya; Calevo, Maria Grazia; Yan, Xiao-Jie; Albesiano, Emilia; Bagnara, Davide; Colombo, Monica; Cutrona, Giovanna; Chu, Charles C; Morabito, Fortunato; Bruno, Silvia; Ferrarini, Manlio; Tramontano, Anna; Fais, Franco; Chiorazzi, Nicholas

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV–diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation. PMID:21785810

  12. Mutation Pattern of Paired Immunoglobulin Heavy and Light Variable Domains in Chronic Lymphocytic Leukemia B Cells

    KAUST Repository

    Ghiotto, Fabio; Marcatili, Paolo

    2011-01-01

    B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated immunoglobulin heavy variable (IGHV ) genes. Most information on CLL immunoglobulins (Igs), such as the definition of stereotyped B-cell receptors (BCRs), was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy- and light-chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hyper-mutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-diversity-joining (IGHV-D-J ) and immunoglobulin kappa/lambda variable-joining (IGK/LV-J ) rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at least one of the two immunoglobulin variable (IGV ) genes (IGHV and/or IGK/LV ). The relationship between the mutation frequency in IGHV and IGK/LV complementarity determining regions (CDRs) and framework regions (FRs) was evaluated by correlation analysis. Replacement (R) mutation frequency within IGK/LV chain CDRs correlated significantly with mutation frequency of paired IGHV CDRs in λ but not κ isotype CLL clones. CDRs of IGKV-J rearrangements displayed a lower percentage of R mutations than IGHVs. The frequency/pattern of mutations in kappa CLL Igs differed also from that in κ-expressing normal B cells described in the literature. Instead, the mutation frequency within the FRs of IGHV and either IGKV or IGLV was correlated. Notably, the amount of diversity introduced by replaced amino acids was comparable between IGHVs and IGKVs. The data indicate a different mutation pattern between κ and λ isotype CLL clones and suggest an antigenic selection that, in κ samples, operates against CDR variation.

  13. Marked improvement by high-dose chemotherapy and autologous stem cell transplantation in a case of light chain deposition disease.

    Science.gov (United States)

    Matsuzaki, Keiichi; Ohsawa, Isao; Nishitani, Tomohito; Takeda, Yukihiko; Inoshita, Hiroyuki; Ishii, Masaya; Takagi, Miyuki; Horikoshi, Satoshi; Tomino, Yasuhiko

    2011-01-01

    A 55-year-old woman presented with heavy proteinuria (6.2 g/day) in April 2007. Because monoclonal IgG-k was detected in serum and urine samples, bone marrow aspiration and renal biopsy were performed. She was diagnosed with plasma cell dyscrasia because a bone marrow aspiration specimen showed plasma cells at 6.1%. Renal tissues revealed the formation of nodular glomerulosclerosis which was negative for Congo-red staining. Renal immunohistochemistry showed positive staining for kappa light chains in the nodular lesions, proximal tubules and part of Bowman's capsules. Her renal involvement was diagnosed as light chain deposition disease. Proteinuria disappeared and renal function stabilized after high-dose chemotherapy and autologous stem cell transplantation. It appears that an early initiation of active therapy such as high-dose chemotherapy and autologous stem cell transplantation may be beneficial for patients with light chain deposition disease.

  14. Investigating the variability in brown carbon light-absorption properties

    Science.gov (United States)

    Saleh, R.; Cheng, Z.; Atwi, K.

    2017-12-01

    Combustion of biomass fuels contributes a significant portion of brown carbon (BrC), the light-absorbing fraction of organic aerosols. BrC exhibits highly variable light-absorption properties, with imaginary part of the refractive indices (k) reported in the literature varying over two orders of magnitude. This high variability in k is attributed to the chaotic nature of combustion; however, there is a major gap in the fundamental understanding of this variability. To address this gap, we hypothesize that BrC is comprised of black carbon (BC) precursors whose transformation to BC has not seen fruition. Depending on the combustion conditions, these BC precursors exhibit different maturity levels which dictate their light-absorption properties (k). The more mature are the precursors, the more absorptive (or BC-like) they are. Therefore, k of BrC obtained from a certain measurement depends on the specific combustion conditions associated with the measurement, leading to the aforementioned variability in the literature. To test this hypothesis, we performed controlled combustion experiments in which the combustion conditions (temperature and air/fuel ratio) were varied and k was retrieved from real-time multi-wavelength light-absorption measurements at each condition. We used benzene, the inception of which during combustion is the initial critical step leading to BC formation, as a model fuel. By varying the combustion conditions from relatively inefficient (low temperature and/or air/fuel ratio) to relatively efficient (high temperature and/or air/fuel ratio), we isolated BrC components with progressively increasing k, spanning the wide range reported in the literature. We also performed thermodenuder measurements to constrain the volatility of the BrC, as well as laser desorption ionization mass spectrometry analysis to constrain its molecular mass. We found that as the combustion conditions approached the BC-formation threshold, the increase in k was associated

  15. Effect of magnetism and light sp-dopants on chain creation in Ir and Pt break junctions

    International Nuclear Information System (INIS)

    Di Napoli, S; Thiess, A; Blügel, S; Mokrousov, Y

    2014-01-01

    Applying the generalization of the model for chain formation in break-junctions (Di Napoli et al 2012 J. Phys.: Condens. Matter 24 135501), we study the effect of light impurities on the energetics and elongation properties of Pt and Ir chains. Our model enables us to develop a tool ideal for detailed analysis of impurity-assisted chain formation, in which zigzag bonds play an important role. In particular we focus on H (s-like) and O (p-like) impurities and assume, for simplicity, that the presence of impurity atoms in experiments results in a ..M-X-M-X-... (M: metal, X: impurity) chain structure in between the metallic leads. Feeding our model with material-specific parameters from systematic full-potential first-principles calculations, we find that the presence of such impurities strongly affects the binding properties of the chains. We find that, while both types of impurities enhance the probability of chains being elongated, the s-like impurities lower the chain's stability. We also analyze the effect of magnetism and spin-orbit interaction on the growth properties of the chains. (paper)

  16. Evaluation of strategies to control Fab light chain dimer during mammalian expression and purification: A universal one-step process for purification of correctly assembled Fab.

    Science.gov (United States)

    Spooner, Jennifer; Keen, Jenny; Nayyar, Kalpana; Birkett, Neil; Bond, Nicholas; Bannister, David; Tigue, Natalie; Higazi, Daniel; Kemp, Benjamin; Vaughan, Tristan; Kippen, Alistair; Buchanan, Andrew

    2015-07-01

    Fabs are an important class of antibody fragment as both research reagents and therapeutic agents. There are a plethora of methods described for their recombinant expression and purification. However, these do not address the issue of excessive light chain production that forms light chain dimers nor do they describe a universal purification strategy. Light chain dimer impurities and the absence of a universal Fab purification strategy present persistent challenges for biotechnology applications using Fabs, particularly around the need for bespoke purification strategies. This study describes methods to address light chain dimer formation during Fab expression and identifies a novel CH 1 affinity resin as a simple and efficient one-step purification for correctly assembled Fab. © 2015 Wiley Periodicals, Inc.

  17. Tunable long-distance light transportation along Au nanoparticle chains: promising for optical interconnect

    Science.gov (United States)

    Lin, Z.; Li, X. D.; Chen, T. P.

    2014-10-01

    Tunable light resonance transportation along a single long Au hemisphere nanoparticles (NPs) chain was studied. The realistic experimentally determined gold dielectric function was used for the simulation of Au localized surface plasmon polariton (LSPPs) effect. The resonance light energy with minimized attenuation and its bandwidth were quantitatively analyzed by inducing the effective mass which was observed to increase only with the length of Au NPs between the source and the test point. The geometric ratio g/ r of NP size and gap were investigated at 5 µm far of NPs with different gaps from 0 to 70 nm. Strongest resonance can be achieved with g/ r = 1.2 by the factor of 1.5 than the connected NPs. This resonance mode falls in the wavelength λ = 555 nm (green light), which is exactly the maximum sensitivity of a light-adapted eye of human beings.

  18. Compositional and expression analyses of the glideosome during the Plasmodium life cycle reveal an additional myosin light chain required for maximum motility.

    Science.gov (United States)

    Green, Judith L; Wall, Richard J; Vahokoski, Juha; Yusuf, Noor A; Ridzuan, Mohd A Mohd; Stanway, Rebecca R; Stock, Jessica; Knuepfer, Ellen; Brady, Declan; Martin, Stephen R; Howell, Steven A; Pires, Isa P; Moon, Robert W; Molloy, Justin E; Kursula, Inari; Tewari, Rita; Holder, Anthony A

    2017-10-27

    Myosin A (MyoA) is a Class XIV myosin implicated in gliding motility and host cell and tissue invasion by malaria parasites. MyoA is part of a membrane-associated protein complex called the glideosome, which is essential for parasite motility and includes the MyoA light chain myosin tail domain-interacting protein (MTIP) and several glideosome-associated proteins (GAPs). However, most studies of MyoA have focused on single stages of the parasite life cycle. We examined MyoA expression throughout the Plasmodium berghei life cycle in both mammalian and insect hosts. In extracellular ookinetes, sporozoites, and merozoites, MyoA was located at the parasite periphery. In the sexual stages, zygote formation and initial ookinete differentiation precede MyoA synthesis and deposition, which occurred only in the developing protuberance. In developing intracellular asexual blood stages, MyoA was synthesized in mature schizonts and was located at the periphery of segmenting merozoites, where it remained throughout maturation, merozoite egress, and host cell invasion. Besides the known GAPs in the malaria parasite, the complex included GAP40, an additional myosin light chain designated essential light chain (ELC), and several other candidate components. This ELC bound the MyoA neck region adjacent to the MTIP-binding site, and both myosin light chains co-located to the glideosome. Co-expression of MyoA with its two light chains revealed that the presence of both light chains enhances MyoA-dependent actin motility. In conclusion, we have established a system to study the interplay and function of the three glideosome components, enabling the assessment of inhibitors that target this motor complex to block host cell invasion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  19. Evaluation of energy efficiency in street lighting: model proposition considering climate variability

    Directory of Open Access Journals (Sweden)

    Amaury Caruzzo

    2015-12-01

    Full Text Available This paper assesses the impacts of climate variability on efficient electricity consumption in street lighting in Brazil. The Climate Demand Method (CDM was applied, and the energy savings achieved by Brazil’s National Efficient Street Lighting Program (ReLuz in 2005 were calculated, considering the monthly climatology of sunshine duration, disaggregated by county in Brazil. The total energy savings in street lighting in 2005 were estimated at 63 GWh/year or 1.39% higher than the value determined by ReLuz/Eletrobrás and there was a 15 MW reduction in demand in Brazil, considering the nearly 393,000 points in ReLuz served in 2005. The results indicate that, besides the difference in latitude, climate variability in different county increases the daily usage of street lighting up to 19%. Furthermore, Brazil’s large size means that seasonality patterns in energy savings are not homogeneous, and there is a correlation between the monthly variability in sunshine duration and the latitude of mesoregions. The CDM was also shown to be suitable for ranking mesoregions with the highest levels of energy saving lighting.

  20. Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

    Science.gov (United States)

    Zhai, Linzhu; Zhao, Yuanyuan; Peng, Songguo; Zhu, Ke; Yu, Rongjian; Chen, Hailong; Lin, Tongyu; Lin, Lizhu

    2016-12-01

    There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

  1. Minimal Essential Domains Specifying Toxicity of the Light Chains of Tetanus Toxin and Botulinum Neurotoxin Type A

    NARCIS (Netherlands)

    Kurazono, Hisao; Mochida, Sumiko; Binz, Thomas; Eisel, Ulrich; Quanz, Martin; Grebenstein, Oliver; Wernars, Karel; Poulain, Bernard; Tauc, Ladislav; Niemann, Heiner

    1992-01-01

    To define conserved domains within the light (L) chains of clostridial neurotoxins, we determined the sequence of botulinum neurotoxin type B (BoNT/B) and aligned it with those of tetanus toxin (TeTx) and BoNT/A, BoNT/Cl, BoNT/D, and BoNT/E. The L chains of BoNT/B and TeTx share 51.6% identical

  2. [The value of serum free light chain in differential diagnosis of monoclonal gammopathy of renal significance].

    Science.gov (United States)

    Li, C; Wen, Y B; Li, H; Su, W; Li, J; Cai, J F; Chen, L M; Li, X M; Li, X W

    2017-08-08

    Objective: To investigate the value of serum free light chain (FLC) in differential diagnosis of monoclonal gammopathy of renal significance (MGRS). Methods: Forty-nine hospitalized patients who underwent renal biopsy in Peking Union Medical College Hospital between January 2013 and December 2015 were included. Monoclonal gammopathy was detected by serum protein electrophoresis (SPE), serum immunofixation electrophoresis (IFE), urine IFE and serum FLC. All patients were classified as MGRS ( n =32) and monoclonal gammopathy of undetermined significance (MGUS) ( n =17). Results: Renal lesions in MGRS subgroup included light chain amyloidosis ( n =24, 75.0%), light chain deposition disease ( n =7, 21.9%), and fibrillary glomerulopathy ( n =1, 3.1%). Renal diseases in MGUS subgroup included membranous nephropathy ( n =10), focal segmental glomerulosclerosi (FSGS) ( n =3), diabetic glomerulopathy ( n =1), Henoch-Schonlein purpura nephritis ( n =1), anti-GBM disease concurrent with membranous nephropathy ( n =1) and glomerulomegaly ( n =1). Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGRS subgroup were 12, 16, 23 and 30, respectively. Positive number of SPE, serum IFE, urine IFE and abnormal number of serum FLC ratio in MGUS subgroup were 11, 17, 6 and 3, respectively. MGRS and MGUS subgroups differed significantly in positive rate of serum IFE ( P value for MGRS, which was helpful for differential diagnosis of patients who had contraindication to renal biopsy.

  3. A strategy for synthesis of pathogenic human immunoglobulin free light chains in E. coli.

    Directory of Open Access Journals (Sweden)

    Paola Rognoni

    Full Text Available Monoclonal immunoglobulin light chains are normally synthesized in excess compared to the heavy chain partners and can be detected in serum and urine ("free" LC. Occasionally free LC are per se cause of organ toxicity, as in free LC-related disorders. In AL amyloidosis, the most common of these conditions, free LC with peculiar biophysical properties related to their primary structure damage target organs and organize in amyloid fibrils. Unlimited availability of well-characterized free LC is instrumental to investigate the toxic effect of these proteins and to study their interactions with targets. We present a straightforward strategy to obtain recombinant monoclonal free LC by using a bacterial system. These proteins, expressed as inclusion bodies, were subjected to solubilization and refolding procedures to recover them in native form. To minimize differences from the circulating natural LC, full-length recombinant LC were expressed, i.e. complete of variable and constant regions, with the original amino acid sequence along the entire protein, and with no purification tags. The strategy was exploited to generate free LC from three AL amyloidosis patients. After purification, recombinant proteins were biochemically characterized and compared to the natural Bence Jones protein isolated from one of the patients. Results showed that the recombinant free LC were properly folded and formed homodimers in solution, similar to the natural Bence Jones protein used for comparison. Furthermore, as proof of pathogenicity, recombinant proteins formed amyloid fibrils in vitro. We believe that the present strategy represents a valuable tool to speed research in free LC-related disorders.

  4. Differential recruitment efficacy of patient-derived amyloidogenic and myeloma light chain proteins by synthetic fibrils-A metric for predicting amyloid propensity.

    Directory of Open Access Journals (Sweden)

    Emily B Martin

    Full Text Available Monoclonal free light chain (LC proteins are present in the circulation of patients with immunoproliferative disorders such as light chain (AL amyloidosis and multiple myeloma (MM. Light chain-associated amyloid is a complex pathology composed of proteinaceous fibrils and extracellular matrix proteins found in all patients with AL and in ~10-30% of patients who presented with MM. Amyloid deposits systemically in multiple organs and tissues leading to dysfunction and ultimately death. The overall survival of patients with amyloidosis is worse than for those with early stage MM.We have developed a sensitive binding assay quantifying the recruitment of full length, patient-derived LC proteins by synthetic amyloid fibrils, as a method for studying their amyloidogenic potential. In a survey of eight urinary LC, both AL and MM-associated proteins were recruited by synthetic amyloid fibrils; however, AL-associated LC bound significantly more efficiently (p < 0.05 than did MM LCs. The LC proteins used in this study were isolated from urine and presumed to represent a surrogate of serum free light chains.The binding of LC to synthetic fibrils in this assay accurately differentiated LC with amyloidogenic propensity from MM LC that were not associated with clinical amyloid disease. Notably, the LC from a MM patient who subsequently developed amyloid behaved as an AL-associated protein in the assay, indicating the possibility for identifying MM patients at risk for developing amyloidosis based on the light chain recruitment efficacy. With this information, at risk patients can be monitored more closely for the development of amyloidosis, allowing timely administration of novel, amyloid-directed immunotherapies-this approach may improve the prognosis for these patients.

  5. Expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori

    NARCIS (Netherlands)

    Joosten, V.; Gouka, R.J.; Hondel, C.A.M.J.J. van den; Verrips, C.T.; Lokman, B.C.

    2005-01-01

    We report the expression and production of llama variable heavy-chain antibody fragments (VHHs) by Aspergillus awamori. Fragments encoding VHHs were cloned in a suitable Aspergillus expression vector and transformants secreting VHH fragments were analysed for integrated gene copy-numbers, mRNA

  6. Pulmonary light-chain deposition disease: CT and pathology findings in nine patients

    International Nuclear Information System (INIS)

    Sheard, S.; Nicholson, A.G.; Edmunds, L.; Wotherspoon, A.C.; Hansell, D.M.

    2015-01-01

    Aim: To review the clinical features of nine patients with pulmonary light-chain deposition disease (LCDD) and record their high-resolution CT (HRCT) and histopathological findings. Materials and methods: Patients with a diagnosis of LCDD on lung biopsy specimen were retrospectively identified. The HRCT characteristics of nodules, cysts, and ancillary findings; change at follow-up; and histopathological findings were documented. Results: Features common to all nine cases were thin-walled cysts. In seven cases, vessels traversing the cysts were identified. The majority of patients (8/9) had at least one pulmonary nodule. There was no zonal predominance of either cysts or nodules. The disease appeared stable in the majority of cases with no serial change in HRCT appearances (5/6 cases with follow-up data, mean duration 29 months). Conclusion: To the authors' knowledge, this is the largest series of pulmonary LCDD patients in the literature, and the first systematic assessment of HRCT findings. Pulmonary cysts are a unifying feature, usually with pulmonary nodules, and serial change on HRCT is unusual. - Highlights: • Nine cases of pulmonary light chain deposition disease with high-resolution CT. • CT scans assessed for abnormal features. • Clinical data and histopathological findings obtained. • All patients had thin-walled cysts on CT, often with traversing vessels. • CT features of disease in this group are cysts, nodules and an indolent course

  7. Characterization of a specific monoclonal antibody against immunoglobulin light kappa/L1 chain in olive flounder (Paralichthys olivaceus)

    DEFF Research Database (Denmark)

    Kim, Young Kyu; Lee, Jung Seok; Jung, Jae Wook

    2017-01-01

    Immunoglobulins (Ig) are heterodimeric proteins that play critical roles in the adaptive immune system of vertebrates. Because of their plasticity, teleostean Igs are more diverse, and thus do not conform to mammalian classifications. Because of this, mammalian-based Ig cell markers cannot be used...... successfully to study immune responses in fish. There is therefore a need to produce Ig-specific cell markers for fish. Here, we attempted to identify the specific isotype detected by an Ig light chain-specific monoclonal antibody (anti-olive flounder IgL-mAb: M7C3-4) that we had previously produced [11......]. Three newly identified sequences of the Ig light chain from olive flounder were classified according to their isotypes. Subsequent analyses revealed that M7C3-4 was able to specifically detect lymphocytes expressing one of the κ chains (Igκ-a) in olive flounder. Interestingly, Igκ-a+ B cells were more...

  8. The role of free kappa and lambda light chains in the pathogenesis and treatment of inflammatory diseases.

    Science.gov (United States)

    Esparvarinha, Mojgan; Nickho, Hamid; Mohammadi, Hamed; Aghebati-Maleki, Leili; Abdolalizadeh, Jalal; Majidi, Jafar

    2017-07-01

    Kappa (κ) or lambda (λ) free light chains (FLCs) are produced from B cells during immunoglobulin synthesis. FLCs have been shown to participate in several key processes of immune responses. They are necessary to adjust PMN functions and assist PMN pre-stimulation. Moreover, they cause mast cell degranulation which releases pro-inflammatory mediators and stimulates local inflammatory responses in some conditions such as inflammatory bowel disease (IBD). Having low molecular weights which may straightly be toxic to proximal tubule cells (PTCs), FLCs can also have an important role in renal diseases. In this review we have highlighted the involvement of light chains in the pathogenesis of some inflammatory diseases and discussed their potential to be the targets of therapeutic purposes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  9. Classification of decays involving variable decay chains with convolutional architectures

    CERN Multimedia

    CERN. Geneva

    2018-01-01

    Vidyo contribution We present a technique to perform classification of decays that exhibit decay chains involving a variable number of particles, which include a broad class of $B$ meson decays sensitive to new physics. The utility of such decays as a probe of the Standard Model is dependent upon accurate determination of the decay rate, which is challenged by the combinatorial background arising in high-multiplicity decay modes. In our model, each particle in the decay event is represented as a fixed-dimensional vector of feature attributes, forming an $n \\times k$ representation of the event, where $n$ is the number of particles in the event and $k$ is the dimensionality of the feature vector. A convolutional architecture is used to capture dependencies between the embedded particle representations and perform the final classification. The proposed model performs outperforms standard machine learning approaches based on Monte Carlo studies across a range of variable final-state decays with the Belle II det...

  10. QUEST1 Variability Survey. II. Variability Determination Criteria and 200k Light Curve Catalog

    Science.gov (United States)

    Rengstorf, A. W.; Mufson, S. L.; Andrews, P.; Honeycutt, R. K.; Vivas, A. K.; Abad, C.; Adams, B.; Bailyn, C.; Baltay, C.; Bongiovanni, A.; Briceño, C.; Bruzual, G.; Coppi, P.; Della Prugna, F.; Emmet, W.; Ferrín, I.; Fuenmayor, F.; Gebhard, M.; Hernández, J.; Magris, G.; Musser, J.; Naranjo, O.; Oemler, A.; Rosenzweig, P.; Sabbey, C. N.; Sánchez, Ge.; Sánchez, Gu.; Schaefer, B.; Schenner, H.; Sinnott, J.; Snyder, J. A.; Sofia, S.; Stock, J.; van Altena, W.

    2004-12-01

    The QUEST (QUasar Equatorial Survey Team) Phase 1 camera has collected multibandpass photometry on a large strip of high Galactic latitude sky over a period of 26 months. This robust data set has been reduced and nightly catalogs compared to determine the photometric variability of the ensemble objects. Subsequent spectroscopic observations have confirmed a subset of the photometric variables as quasars, as previously reported. This paper reports on the details of the data reduction and analysis pipeline and presents multiple bandpass light curves for 198,213 QUEST1 objects, along with global variability information and matched Sloan photometry. Based on observations obtained at the Llano del Hato National Astronomical Observatory, operated by the Centro de Investigaciones de Astronomía for the Ministerio de Ciencia y Tecnologia of Venezuela.

  11. Excitation of random intense single-cycle light-pulse chains in optical fiber

    International Nuclear Information System (INIS)

    Ding, Y C; Zhang, F L; Gao, J B; Chen, Z Y; Lin, C Y; Yu, M Y

    2014-01-01

    Excitation of intense periodic single-cycle light pulses in a stochastic background arising from continuous wave stimulated Brillouin scattering (SBS) in a long optical fiber with weak optical feedback is found experimentally and modeled theoretically. Such intense light-pulse chains occur randomly and the optical feedback is a requirement for their excitation. The probability of these forms, among the large number of experimental output signals with identifiable waveforms, appearing is only about 3%, with the remainder exhibiting regular SBS characteristics. It is also found that pulses with low period numbers appear more frequently and the probability distribution for their occurrence in terms of the pulse power is roughly L-shaped, like that for rogue waves. The results from a three-wave-coupling model for SBS including feedback phase control agree well qualitatively with the observed phenomena. (paper)

  12. Tissue Specific Roles of Dynein Light Chain 1 in Regulating Germ Cell Apoptosis in Ceanorhabditis elegans

    DEFF Research Database (Denmark)

    Morthorst, Tine Hørning

    2015-01-01

    in the etiology of many diseases, including cancer, neurodegenerative, cardiovascular and autoimmune diseases. Several of the first genes found to regulate apoptosis were discovered in the nematode Caenorhabditis elegans. In this project, two different and tissue specific roles of C. elegans dynein light chain 1...

  13. Dynamics of a linear system coupled to a chain of light nonlinear oscillators analyzed through a continuous approximation

    Science.gov (United States)

    Charlemagne, S.; Ture Savadkoohi, A.; Lamarque, C.-H.

    2018-07-01

    The continuous approximation is used in this work to describe the dynamics of a nonlinear chain of light oscillators coupled to a linear main system. A general methodology is applied to an example where the chain has local nonlinear restoring forces. The slow invariant manifold is detected at fast time scale. At slow time scale, equilibrium and singular points are sought around this manifold in order to predict periodic regimes and strongly modulated responses of the system. Analytical predictions are in good accordance with numerical results and represent a potent tool for designing nonlinear chains for passive control purposes.

  14. A Single-Chain Photoswitchable CRISPR-Cas9 Architecture for Light-Inducible Gene Editing and Transcription.

    Science.gov (United States)

    Zhou, Xin X; Zou, Xinzhi; Chung, Hokyung K; Gao, Yuchen; Liu, Yanxia; Qi, Lei S; Lin, Michael Z

    2018-02-16

    Optical control of CRISPR-Cas9-derived proteins would be useful for restricting gene editing or transcriptional regulation to desired times and places. Optical control of Cas9 functions has been achieved with photouncageable unnatural amino acids or by using light-induced protein interactions to reconstitute Cas9-mediated functions from two polypeptides. However, these methods have only been applied to one Cas9 species and have not been used for optical control of different perturbations at two genes. Here, we use photodissociable dimeric fluorescent protein domains to engineer single-chain photoswitchable Cas9 (ps-Cas9) proteins in which the DNA-binding cleft is occluded at baseline and opened upon illumination. This design successfully controlled different species and functional variants of Cas9, mediated transcriptional activation more robustly than previous optogenetic methods, and enabled light-induced transcription of one gene and editing of another in the same cells. Thus, a single-chain photoswitchable architecture provides a general method to control a variety of Cas9-mediated functions.

  15. Myosin light chain phosphorylation is critical for adaptation to cardiac stress.

    Science.gov (United States)

    Warren, Sonisha A; Briggs, Laura E; Zeng, Huadong; Chuang, Joyce; Chang, Eileen I; Terada, Ryota; Li, Moyi; Swanson, Maurice S; Lecker, Stewart H; Willis, Monte S; Spinale, Francis G; Maupin-Furlowe, Julie; McMullen, Julie R; Moss, Richard L; Kasahara, Hideko

    2012-11-27

    Cardiac hypertrophy is a common response to circulatory or neurohumoral stressors as a mechanism to augment contractility. When the heart is under sustained stress, the hypertrophic response can evolve into decompensated heart failure, although the mechanism(s) underlying this transition remain largely unknown. Because phosphorylation of cardiac myosin light chain 2 (MLC2v), bound to myosin at the head-rod junction, facilitates actin-myosin interactions and enhances contractility, we hypothesized that phosphorylation of MLC2v plays a role in the adaptation of the heart to stress. We previously identified an enzyme that predominantly phosphorylates MLC2v in cardiomyocytes, cardiac myosin light-chain kinase (cMLCK), yet the role(s) played by cMLCK in regulating cardiac function in health and disease remain to be determined. We found that pressure overload induced by transaortic constriction in wild-type mice reduced phosphorylated MLC2v levels by ≈40% and cMLCK levels by ≈85%. To examine how a reduction in cMLCK and the corresponding reduction in phosphorylated MLC2v affect function, we generated Mylk3 gene-targeted mice and transgenic mice overexpressing cMLCK specifically in cardiomyocytes. Pressure overload led to severe heart failure in cMLCK knockout mice but not in mice with cMLCK overexpression in which cMLCK protein synthesis exceeded degradation. The reduction in cMLCK protein during pressure overload was attenuated by inhibition of ubiquitin-proteasome protein degradation systems. Our results suggest the novel idea that accelerated cMLCK protein turnover by the ubiquitin-proteasome system underlies the transition from compensated hypertrophy to decompensated heart failure as a result of reduced phosphorylation of MLC2v.

  16. Longitudinal left ventricular function for prediction of survival in systemic light-chain amyloidosis: incremental value compared with clinical and biochemical markers.

    Science.gov (United States)

    Buss, Sebastian J; Emami, Mostafa; Mereles, Derliz; Korosoglou, Grigorios; Kristen, Arnt V; Voss, Andreas; Schellberg, Dieter; Zugck, Christian; Galuschky, Christian; Giannitsis, Evangelos; Hegenbart, Ute; Ho, Anthony D; Katus, Hugo A; Schonland, Stefan O; Hardt, Stefan E

    2012-09-18

    The aim of the study was to determine whether longitudinal left ventricular (LV) function provides prognostic information in a large cohort of patients with systemic light-chain (AL) amyloidosis. AL amyloidosis is associated with a high incidence of cardiovascular events. Reduced myocardial longitudinal function is one of the hallmarks of myocardial involvement in this rare disease. Two hundred six consecutive patients with biopsy-proven AL amyloidosis were investigated in this prospective observational study. Echocardiographic imaging parameters, mean tissue Doppler-derived longitudinal strain (LS), and two-dimensional global longitudinal strain (2D-GLS) of the LV, cardiac serological biomarkers, and comprehensive clinical disease characteristics were assessed. The primary endpoint was all-cause mortality or heart transplantation. After a median follow-up of 1207 days, LS and 2D-GLS were significant predictors of survival in AL amyloidosis. The cutoff values discriminating survivors from nonsurvivors were -10.65% for LS and -11.78% for 2D-GLS. In a multivariable echocardiographic Cox model, only diastolic dysfunction and 2D-GLS remained as independent predictors of survival. In comprehensive clinical models, 2D-GLS (p < 0.0001), diastolic dysfunction (p < 0.01), the pathologic free light chains (p < 0.05), cardiac troponin-T (cTnT) (p < 0.01), and the Karnofsky index (p < 0.001) remained as independent predictors. 2D-GLS delineated a superior prognostic value compared with that derived from pathologic free light chains or cTnT in patients evaluated before firstline chemotherapy (n = 113; p < 0.0001), and remained the only independent predictor besides the Karnofsky index in subjects with preserved LV ejection fraction (≥50%; n = 127; p < 0.01). LS and 2D-GLS both offered significant incremental information (p < 0.001) for the assessment of outcome compared with clinical variables (age, Karnofsky index, and New York Heart Association functional class) and

  17. Age- and Activity-Related Differences in the Abundance of Myosin Essential and Regulatory Light Chains in Human Muscle

    Directory of Open Access Journals (Sweden)

    James N. Cobley

    2016-04-01

    Full Text Available Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM. We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.

  18. A Strategy for Generating a Broad-Spectrum Monoclonal Antibody and Soluble Single-Chain Variable Fragments against Plant Potyviruses

    Science.gov (United States)

    Liu, Han-Lin; Lin, Wei-Fang; Hu, Wen-Chi; Lee, Yung-An

    2015-01-01

    Potyviruses are major pathogens that often cause mixed infection in calla lilies. To reduce the time and cost of virus indexing, a detection method for the simultaneous targeting of multiple potyviruses was developed by generating a broad-spectrum monoclonal antibody (MAb) for detecting the greatest possible number of potyviruses. The conserved 121-amino-acid core regions of the capsid proteins of Dasheen mosaic potyvirus (DsMV), Konjak mosaic potyvirus (KoMV), and Zantedeschia mild mosaic potyvirus (ZaMMV) were sequentially concatenated and expressed as a recombinant protein for immunization. After hybridoma cell fusion and selection, one stable cell line that secreted a group-specific antibody, named C4 MAb, was selected. In the reaction spectrum test, the C4 MAb detected at least 14 potyviruses by indirect enzyme-linked immunosorbent assay (I-ELISA) and Western blot analysis. Furthermore, the variable regions of the heavy (VH) and light (VL) chains of the C4 MAb were separately cloned and constructed as single-chain variable fragments (scFvs) for expression in Escherichia coli. Moreover, the pectate lyase E (PelE) signal peptide of Erwinia chrysanthemi S3-1 was added to promote the secretion of C4 scFvs into the medium. According to Western blot analysis and I-ELISA, the soluble C4 scFv (VL-VH) fragment showed a binding specificity similar to that of the C4 MAb. Our results demonstrate that a recombinant protein derived from fusion of the conserved regions of viral proteins has the potential to produce a broad-spectrum MAb against a large group of viruses and that the PelE signal peptide can improve the secretion of scFvs in E. coli. PMID:26209665

  19. Increased myosin heavy chain-beta with atrial expression of ventricular light chain-2 in canine cardiomyopathy.

    Science.gov (United States)

    Fuller, Geraldine A; Bicer, Sabahattin; Hamlin, Robert L; Yamaguchi, Mamoru; Reiser, Peter J

    2007-10-01

    Dilated cardiomyopathy is a naturally occurring disease in humans and dogs. Human studies have shown increased levels of myosin heavy chain (MHC)-beta in failing ventricles and the left atria (LA) and of ventricular light chain (VLC)-2 in the right atria in dilated cardiomyopathy. This study evaluates the levels of MHC-beta in all heart chambers in prolonged canine right ventricular pacing. In addition, we determined whether levels of VLC2 were altered in these hearts. Failing hearts demonstrated significantly increased levels of MHC-beta in the right atria, right atrial appendage, LA, left atrial appendage (LAA), and right ventricle compared with controls. Significant levels of VLC2 were detected in the right atria of paced hearts. Differences in MHC-beta expression were observed between the LA and the LAA of paced and control dogs. MHC-beta expression was significantly greater in the LA of paced and control dogs compared with their respective LAA. The cardiac myosin isoform shifts in this study were similar to those observed in end-stage human heart failure and more severe than those reported in less prolonged pacing models, supporting the use of this model for further study of end-stage human heart failure. The observation of consistent differences between sampling sites, especially LA versus LAA, indicates the need for rigorous sampling consistency in future studies.

  20. Shark Ig light chain junctions are as diverse as in heavy chains.

    Science.gov (United States)

    Fleurant, Marshall; Changchien, Lily; Chen, Chin-Tung; Flajnik, Martin F; Hsu, Ellen

    2004-11-01

    We have characterized a small family of four genes encoding one of the three nurse shark Ig L chain isotypes, called NS5. All NS5 cDNA sequences are encoded by three loci, of which two are organized as conventional clusters, each consisting of a V and J gene segment that can recombine and one C region exon; the third contains a germline-joined VJ in-frame and the fourth locus is a pseudogene. This is the second nurse shark L chain type where both germline-joined and split V-J organizations have been found. Since there are only two rearranging Ig loci, it was possible for the first time to examine junctional diversity in defined fish Ig genes, comparing productive vs nonproductive rearrangements. N region addition was found to be considerably more extensive in length and in frequency than any other vertebrate L chain so far reported and rivals that in H chain. We put forth the speculation that the unprecedented efficiency of N region addition (87-93% of NS5 sequences) may be a result not only of simultaneous H and L chain rearrangement in the shark but also of processing events that afford greater accessibility of the V or J gene coding ends to terminal deoxynucleotidyltransferase.

  1. Successful treatment of nephrotic syndrome induced by lambda light chain deposition disease using lenalidomide: A case report and review of the literature
.

    Science.gov (United States)

    Mima, Akira; Nagahara, Dai; Tansho, Kosuke

    2018-06-01

    Light chain deposition disease (LCDD) is a monoclonal immunoglobulin deposition disease (MIDD) that is characterized by the deposition of monoclonal light chains in multiple organs, including the kidney. It is a rare disorder caused by an underlying monoclonal plasma cell dyscrasia. LCDD with renal involvement causes proteinuria, which sometimes can lead to nephrotic syndrome. The monoclonal light chains are mostly in the κ form. Treatment of LCDD is the same as that for multiple myeloma (MM); however, some conventional anticancer drugs show substantial toxicity and therefore cannot be administered to older patients or those with renal impairment. An 80-year-old woman was referred to our department with severe nephrotic syndrome (13.6 g/gCr) and anemia. A renal biopsy showed mesangial proliferation and mesangial matrix expansion, and immunohistochemistry showed positive staining for λ chains along the glomerular basement membrane, but was negative for κ chains or amyloid deposition. A bone marrow biopsy revealed 64% plasma cells. Immunoglobulin G (IgG)-λ type M protein was detected, and the levels of free λ chain was significantly increased. We concluded that her nephrotic syndrome was caused by LCDD, which resulted from IgG-λ MM. The induction of a BCD (bortezomib, cyclophosphamide, and dexamethasone) treatment regimen did not lead to a hematological response or decrease in proteinuria. The administration of combination therapy of lenalidomide and prednisolone led to the successful reduction of proteinuria and hematuria. We presented a very rare case report describing the successful treatment of LCDD (λ chain)-induced nephrotic syndrome with lenalidomide.
.

  2. New construction of eigenstates and separation of variables for SU( N) quantum spin chains

    Science.gov (United States)

    Gromov, Nikolay; Levkovich-Maslyuk, Fedor; Sizov, Grigory

    2017-09-01

    We conjecture a new way to construct eigenstates of integrable XXX quantum spin chains with SU( N) symmetry. The states are built by repeatedly acting on the vacuum with a single operator B good( u) evaluated at the Bethe roots. Our proposal serves as a compact alternative to the usual nested algebraic Bethe ansatz. Furthermore, the roots of this operator give the separated variables of the model, explicitly generalizing Sklyanin's approach to the SU( N) case. We present many tests of the conjecture and prove it in several special cases. We focus on rational spin chains with fundamental representation at each site, but expect many of the results to be valid more generally.

  3. Porous silicon biosensor for detection of variable domain of heavy-chain of HCAb antibody

    Science.gov (United States)

    Zhang, Hong-yan; Lü, Xiao-yi; Jia, Zhen-hong; Li, Jiang-wei; Zhang, Fu-chun

    2012-03-01

    In this paper, we produce porous silicon (PSi) by electrochemical etching, and it is the first time to evaluate the performance of label-free porous silicon biosensor for detection of variable domain of heavy chain of heavy-chain antibody (VHH). The binding of hen egg white lysozyme (HEWL) and VHH causes a red shift in the reflection spectrum of the biosensor. The red shift is proportional to the VHH concentration in the range from 14 g·ml-1 to 30 g·ml-1 with a detection limit of 0.648 ng·ml-1. The research is useful for the development of label-free biosensor applied in the rapid and sensitive determination of small molecules.

  4. Cerebrospinal fluid neurofilament light chain levels predict visual outcome after optic neuritis

    DEFF Research Database (Denmark)

    Modvig, Signe; Degn, M; Sander, B

    2016-01-01

    BACKGROUND: Optic neuritis is a good model for multiple sclerosis relapse, but currently no tests can accurately predict visual outcome. OBJECTIVE: The purpose of this study was to examine whether cerebrospinal fluid (CSF) biomarkers of tissue damage and remodelling (neurofilament light chain (NF......-L, β=-1.1, p=0.0150 for GC-IPL). Complete/incomplete remission was determined based on LCVA from 30 healthy controls. NF-L had a positive predictive value of 91% and an area under the curve (AUC) of 0.79 for incomplete remission. CONCLUSION: CSF NF-L is a promising biomarker of visual outcome after...

  5. CHARACTERIZATION OF TIGHTLY-ASSOCIATED SMOOTH MUSCLE MYOSIN-MYOSIN LIGHT CHAIN KINASE-CALMODULIN COMPLEXES*

    OpenAIRE

    Hong, Feng; Haldeman, Brian D.; John, Olivia A.; Brewer, Paul D.; Wu, Yi-Ying; Ni, Shaowei; Wilson, David P.; Walsh, Michael P.; Baker, Jonathan E.; Cremo, Christine R.

    2009-01-01

    A current popular model to explain phosphorylation of smooth muscle myosin (SMM) by smooth muscle myosin light chain kinase (MLCK) proposes that MLCK is bound tightly to actin but weakly to SMM. We found that MLCK and calmodulin (CaM) co-purify with unphosphorylated SMM (up-SMM) from chicken gizzard, suggesting that they are tightly bound. Although the MLCK:SMM molar ratio in SMM preparations was well below stoichiometric (1:73 ± 9), the ratio was ~ 23–37% of that in gizzard tissue. Fifteen t...

  6. Enhancing lean supply chain through traffic light quality management system

    Directory of Open Access Journals (Sweden)

    Md. Mazharul Islam

    2013-03-01

    Full Text Available Lean is a continuous journey to grow and excel the company. Any company want to develop and cope with the world pace must adopt lean. However, in most of the organizations the management culture or people’s mentality is not so good to embrace change. They have predestined mind set where no change is normally allowed. Lean is a cooperative way of working that involves all departments and all personnel to work together in a team for the betterment of the entire company. Without providing fixed solution of any problem it suggests the best way that people willingly accept to do. Lean normally deals with highest quality, shorter lead time and lowest cost. In Bangladesh, most of the garment manufacturing companies are experiencing a massive quality problem. We describe a case where traffic light, a tool of lean quality system was adopted to a garment manufacturing company in Bangladesh. We also provide the charts to contrast the before and after scenario in detail, in order to illustrate the company benefits. After the traffic light system being implemented, the quality status was improved, production capacity was increased; significant days were saved that enhanced the lead time and thus strengthen the supply chain.

  7. Light Scattering Study of Mixed Micelles Made from Elastin-Like Polypeptide Linear Chains and Trimers

    Science.gov (United States)

    Terrano, Daniel; Tsuper, Ilona; Maraschky, Adam; Holland, Nolan; Streletzky, Kiril

    Temperature sensitive nanoparticles were generated from a construct (H20F) of three chains of elastin-like polypeptides (ELP) linked to a negatively charged foldon domain. This ELP system was mixed at different ratios with linear chains of ELP (H40L) which lacks the foldon domain. The mixed system is soluble at room temperature and at a transition temperature (Tt) will form swollen micelles with the hydrophobic linear chains hidden inside. This system was studied using depolarized dynamic light scattering (DDLS) and static light scattering (SLS) to determine the size, shape, and internal structure of the mixed micelles. The mixed micelle in equal parts of H20F and H40L show a constant apparent hydrodynamic radius of 40-45 nm at the concentration window from 25:25 to 60:60 uM (1:1 ratio). At a fixed 50 uM concentration of the H20F, varying H40L concentration from 5 to 80 uM resulted in a linear growth in the hydrodynamic radius from about 11 to about 62 nm, along with a 1000-fold increase in VH signal. A possible simple model explaining the growth of the swollen micelles is considered. Lastly, the VH signal can indicate elongation in the geometry of the particle or could possibly be a result from anisotropic properties from the core of the micelle. SLS was used to study the molecular weight, and the radius of gyration of the micelle to help identify the structure and morphology of mixed micelles and the tangible cause of the VH signal.

  8. Period of Light Variability in BL Lac ON 231 Xu Yun Bing1, Zhang ...

    Indian Academy of Sciences (India)

    period light variability may be greater than the current observation history and needs further monitoring certification (Zhang et al. 1998). To establish the real periods of ON 231, we employ wavelet analysis and DCF method to search a periodicity in the light curves. 2. Periodicity analysis of ON231. 2.1 Light curve of ON 231.

  9. A Novel, In-solution Separation of Endogenous Cardiac Sarcomeric Proteins and Identification of Distinct Charged Variants of Regulatory Light Chain*

    Science.gov (United States)

    Scruggs, Sarah B.; Reisdorph, Rick; Armstrong, Mike L.; Warren, Chad M.; Reisdorph, Nichole; Solaro, R. John; Buttrick, Peter M.

    2010-01-01

    The molecular conformation of the cardiac myosin motor is modulated by intermolecular interactions among the heavy chain, the light chains, myosin binding protein-C, and titin and is governed by post-translational modifications (PTMs). In-gel digestion followed by LC/MS/MS has classically been applied to identify cardiac sarcomeric PTMs; however, this approach is limited by protein size, pI, and difficulties in peptide extraction. We report a solution-based work flow for global separation of endogenous cardiac sarcomeric proteins with a focus on the regulatory light chain (RLC) in which specific sites of phosphorylation have been unclear. Subcellular fractionation followed by OFFGEL electrophoresis resulted in isolation of endogenous charge variants of sarcomeric proteins, including regulatory and essential light chains, myosin heavy chain, and myosin-binding protein-C of the thick filament. Further purification of RLC using reverse-phase HPLC separation and UV detection enriched for RLC PTMs at the intact protein level and provided a stoichiometric and quantitative assessment of endogenous RLC charge variants. Digestion and subsequent LC/MS/MS unequivocally identified that the endogenous charge variants of cardiac RLC focused in unique OFFGEL electrophoresis fractions were unphosphorylated (78.8%), singly phosphorylated (18.1%), and doubly phosphorylated (3.1%) RLC. The novel aspects of this study are that 1) milligram amounts of endogenous cardiac sarcomeric subproteome were focused with resolution comparable with two-dimensional electrophoresis, 2) separation and quantification of post-translationally modified variants were achieved at the intact protein level, 3) separation of intact high molecular weight thick filament proteins was achieved in solution, and 4) endogenous charge variants of RLC were separated; a novel doubly phosphorylated form was identified in mouse, and singly phosphorylated, singly deamidated, and deamidated/phosphorylated forms were

  10. Targeting nanodisks via a single chain variable antibody - Apolipoprotein chimera

    International Nuclear Information System (INIS)

    Iovannisci, David M.; Beckstead, Jennifer A.; Ryan, Robert O.

    2009-01-01

    Nanodisks (ND) are nanometer scale complexes of phospholipid and apolipoprotein that have been shown to function as drug delivery vehicles. ND harboring significant quantities of the antifungal agent, amphotericin B, or the bioactive isoprenoid, all trans retinoic acid, have been generated and characterized. As currently formulated, ND possess limited targeting capability. In this study, we constructed a single chain variable antibody (scFv).apolipoprotein chimera and assessed the ability of this fusion protein to form ND and recognize the antigen to which the scFv is directed. Data obtained revealed that α-vimentin scFv.apolipoprotein A-I is functional in ND formation and antigen recognition, opening the door to the use of such chimeras in targeting drug-enriched ND to specific tissues.

  11. Hypermutation in shark immunoglobulin light chain genes results in contiguous substitutions.

    Science.gov (United States)

    Lee, Susan S; Tranchina, Daniel; Ohta, Yuko; Flajnik, Martin F; Hsu, Ellen

    2002-04-01

    Among 631 substitutions present in 90 nurse shark immunoglobulin light chain somatic mutants, 338 constitute 2-4 bp stretches of adjacent changes. An absence of mutations in perinatal sequences and the bias for one mutating V gene in adults suggest that the diversification is antigen dependent. The substitutions shared no patterns, and the absence of donor sequences, including from family members, supports the idea that most changes arose from nontemplated mutation. The tandem mutations as a group are distinguished by consistently fewer transition changes and an A bias. We suggest this is one of several pathways of hypermutation diversifying shark antigen-receptor genes--point mutations, tandem mutations, and mutations with a G-C preference--that coevolved with or preceded gene rearrangement.

  12. A Model of the Temporal Variability of Optical Light from Extrasolar Terrestrial Planets

    OpenAIRE

    Ford, Eric B.; Seager, Sara; Turner, Edwin L.

    2002-01-01

    The light scattered by an extrasolar Earth-like planet's surface and atmosphere will vary in intensity and color as the planet rotates; the resulting light curve will contain information about the planet's properties. Since most of the light comes from a small fraction of the planet's surface, the temporal flux variability can be quite significant, $\\sim$ 10-100%. In addition, for cloudless Earth-like extrasolar planet models, qualitative changes to the surface (such as ocean fraction, ice co...

  13. Prognostic value of free light chains lambda and kappa in early multiple sclerosis.

    Science.gov (United States)

    Voortman, Margarete M; Stojakovic, Tatjana; Pirpamer, Lukas; Jehna, Margit; Langkammer, Christian; Scharnagl, Hubert; Reindl, Markus; Ropele, Stefan; Seifert-Held, Thomas; Archelos, Juan-Jose; Fuchs, Siegrid; Enzinger, Christian; Fazekas, Franz; Khalil, Michael

    2017-10-01

    Cerebrospinal fluid (CSF) immunoglobulin free light chains (FLC) have been suggested as quantitative alternative to oligoclonal bands (OCB) in the diagnosis of multiple sclerosis (MS). However, little is known on their role in predicting clinical and paraclinical disease progression, particularly in early stages. To assess the prognostic value of FLC in OCB-positive patients with clinically isolated syndrome (CIS) suggestive of MS and early MS. We determined FLC kappa (KFLC) and lambda (LFLC) in CSF and serum by nephelometry in 61 patients (CIS ( n = 48), relapsing-remitting multiple sclerosis ( n = 13)) and 60 non-inflammatory neurological controls. Median clinical follow-up time in CIS was 4.8 years (interquartile range (IQR), 1.5-6.5 years). Patients underwent 3T magnetic resonance imaging (MRI) at baseline and follow-up (median time interval, 2.2 years; IQR, 1.0-3.7 years) to determine T2 lesion load (T2LL) and percent brain volume change (PBVC). CSF FLC were significantly increased in CIS/MS compared to controls (all p multiple sclerosis (CDMS) conversion (hazard ratio (HR) = 2.89; 95% confidence interval (CI) = 1.17-7.14; p < 0.05). No correlations were found for FLC variables with T2LL or PBVC. Our study confirms increased intrathecal synthesis of FLC in CIS/MS which supports their diagnostic contribution. The KFLC/LFLC CSF ratio appears to have a prognostic value in CIS beyond OCB.

  14. Tubulointerstitial nephritis accompanying gamma-heavy chain deposition and gamma-heavy chain restricted plasma cells in the kidney.

    Science.gov (United States)

    Nayer, Ali; Green, Dollie F; Gonzalez-Suarez, Maria L; Sujoy, Victoria; Ikpatt, Offiong F; Thomas, David B

    2014-09-01

    Monoclonal immunoglobulin heavy chain (HC) diseases are rare proliferative disorders of B lymphocytes or plasma cells characterized by the presence of monoclonal α-, µ-, or γ-HC without associated light chains in the blood, urine, or both. We report a 59-year-old woman with a history of Hodgkin disease who developed hypercalcemia, proteinuria, and impaired kidney function. Protein electrophoresis and immunofixation displayed γ-HC without associated light chains in the serum and urine. Pathologic examination demonstrated severe tubulointerstitial nephritis associated with diffuse and strong linear staining of the glomerular and tubular basement membranes as well as Bowman capsules for γ-HC, but not for κ- or λ-light chains. Immunohistochemical examination of the kidney and bone marrow demonstrated numerous CD138+ plasma cells immunoreactive for γ-HC, but not for κ- or λ-light chains. This is the first report of tubulointerstitial nephritis associated with γ-HC deposition and γ-HC restricted plasma cells in the kidney. This report heightens awareness about tubulointerstitial nephritis as a possible manifestation of γ-HC deposition in the kidney.

  15. Size variability of the unit building block of peripheral light-harvesting antennas as a strategy for effective functioning of antennas of variable size that is controlled in vivo by light intensity.

    Science.gov (United States)

    Taisova, A S; Yakovlev, A G; Fetisova, Z G

    2014-03-01

    This work continuous a series of studies devoted to discovering principles of organization of natural antennas in photosynthetic microorganisms that generate in vivo large and highly effective light-harvesting structures. The largest antenna is observed in green photosynthesizing bacteria, which are able to grow over a wide range of light intensities and adapt to low intensities by increasing of size of peripheral BChl c/d/e antenna. However, increasing antenna size must inevitably cause structural changes needed to maintain high efficiency of its functioning. Our model calculations have demonstrated that aggregation of the light-harvesting antenna pigments represents one of the universal structural factors that optimize functioning of any antenna and manage antenna efficiency. If the degree of aggregation of antenna pigments is a variable parameter, then efficiency of the antenna increases with increasing size of a single aggregate of the antenna. This means that change in degree of pigment aggregation controlled by light-harvesting antenna size is biologically expedient. We showed in our previous work on the oligomeric chlorosomal BChl c superantenna of green bacteria of the Chloroflexaceae family that this principle of optimization of variable antenna structure, whose size is controlled by light intensity during growth of bacteria, is actually realized in vivo. Studies of this phenomenon are continued in the present work, expanding the number of studied biological materials and investigating optical linear and nonlinear spectra of chlorosomes having different structures. We show for oligomeric chlorosomal superantennas of green bacteria (from two different families, Chloroflexaceae and Oscillochloridaceae) that a single BChl c aggregate is of small size, and the degree of BChl c aggregation is a variable parameter, which is controlled by the size of the entire BChl c superantenna, and the latter, in turn, is controlled by light intensity in the course of cell

  16. Retinal pigment epithelial detachments and tears, and progressive retinal degeneration in light chain deposition disease.

    Science.gov (United States)

    Spielberg, Leigh H; Heckenlively, John R; Leys, Anita M

    2013-05-01

    Light-chain deposition disease (LCDD) is a rare condition characterised by deposition of monoclonal immunoglobulin light chains (LCs) in tissues, resulting in varying degrees of organ dysfunction. This study reports the characteristic clinical ocular findings seen in advanced LCDD upon development of ocular fundus changes. This is the first report to describe this entity in vivo in a series of patients. A case series of ocular fundus changes in three patients with kidney biopsy-proven LCDD. All patients underwent best corrected visual acuity (BCVA) exam, perimetry, colour fundus photography and fluorescein angiography; two patients underwent indocyanine green angiography, optical coherence tomography, ultrasound and electroretinography; and one patient underwent fundus autofluorescence. Three patients, 53-60 years old at initial presentation, were studied. All three presented with night blindness, poor dark adaptation, metamorphopsia and visual loss. Examination revealed serous and serohaemorrhagic detachments, multiple retinal pigment epithelial (RPE) tears, diffuse RPE degeneration and progressive fibrotic changes. Neither choroidal neovascularisation nor other vascular abnormalities were present. Final best corrected visual acuity (BCVA) ranged from 20/40 to 20/300. Progressive LC deposition in the fundus seems to damage RPE pump function with flow disturbance between choroid and retina. This pathogenesis can explain the evolution to RPE detachments and subsequent rips and progressive retinal malfunction.

  17. The normally expressed kappa immunoglobulin light chain gene repertoire and somatic mutations studied by single-sided specific polymerase chain reaction (PCR); frequent occurrence of features often assigned to autoimmunity

    DEFF Research Database (Denmark)

    Juul, L; Hougs, L; Andersen, V

    1997-01-01

    The expressed human kappa light chain gene repertoire utilized by healthy individuals was studied by two different single-sided specific PCR techniques to avoid bias for certain V genes. A total of 103 rearranged kappa sequences from peripheral blood mononuclear cells from healthy individuals were...

  18. BstXI RFLP in the human inter-alpha-trypsin inhibitor light chain gene

    Energy Technology Data Exchange (ETDEWEB)

    Leveillard, T; Bourguignon, J; Sesbouee, R; Hanauer, A; Salier, J P; Diarra-Mehrpour, M; Martin, J P

    1988-03-25

    The 1.2 kb EcoRI/SmaI fragment of lambdaHuLITI2 was used as probe. lambdaHuLITI2 is a full length cDNA clone coding for human inter-alpha-trypsin inhibitor light chain isolated from immunochemical screening of a lambdagt11 library. Its sequence coding for HI-30 and alpha-1-microglobulin is in agreement. BstXI identifies five invariant bands at 5.0 kb, 2.3 kb, 1.5 kb, 1.1 kb, and 0.7 kb and a diallelic polymorphism with DNA fragments at 2.0 kb or 1.7 kb.

  19. Mechanical Defects of Muscle Fibers with Myosin Light Chain Mutants that Cause Cardiomyopathy

    OpenAIRE

    Roopnarine, Osha

    2003-01-01

    Familial hypertrophic cardiomyopathy is a disease caused by single mutations in several sarcomeric proteins, including the human myosin ventricular regulatory light chain (vRLC). The effects of four of these mutations (A13T, F18L, E22K, and P95A) in vRLC on force generation were determined as a function of Ca2+ concentration. The endogenous RLC was removed from skinned rabbit psoas muscle fibers, and replaced with either rat wildtype vRLC or recombinant rat vRLC (G13T, F18L, E22K, and P95A). ...

  20. An analysis of the variables that provide a supply chain with sustainable competitiveness An analysis of the variables that provide a supply chain with sustainable competitiveness Análisis de las variables que proporcionan una competitividad sostenible de la cadena de suministro

    Directory of Open Access Journals (Sweden)

    José A.D. Machuca

    2012-04-01

    Full Text Available Purpose: An agile, adaptable and aligned (Triple A supply chain (SC would seem to be key to obtaining sustainable competitive advantages. Little previous research has been done into the topic, however, and there are even discrepancies on the conceptual level. For this reason this study aims to propose a reference framework to determine the dimensions and factors that define agility, adaptability and alignment in the SC and to facilitate both the evaluation of its state by managers and researchers with respect to these variables and also the development of empirical research that determines its impact on performance.Design/methodology: A systematic literature review was carried out of specialist Operations Management, Logistics, Management and Supply Chain Management journals using the ProQuest (Abi/Inform Global database. The articles retrieved were examined and those that were relevant for this study were selected. Using these, a qualitative analysis was done that led to the proposed goal being achieved. Findings: This study sets out the definitions, dimensions and factors of the three variables and groups them together for the first time, thus providing a solid conceptual frame. Although the number of articles that analyse one or other of the variables is growing, it is still low. Agility is the variable on which most research has been done, while adaptability is the least analysed.Research limitations/implications: A theoretical reference framework is proposed for the Triple A in the SC based on earlier studies which do not discuss the joint effect of three variables, as a result of which there is no tested theoretical base. The model will be analysed empirically in future research.Originality/value: The lack of papers on agility, adaptability and alignment in the supply chain and the lack of a consensus regarding the dimensions and factors to define them reveal a need for studies such as this. Normal 0 21 false false false Microsoft

  1. β-Arrestin regulation of myosin light chain phosphorylation promotes AT1aR-mediated cell contraction and migration.

    Directory of Open Access Journals (Sweden)

    Elie Simard

    Full Text Available Over the last decade, it has been established that G-protein-coupled receptors (GPCRs signal not only through canonical G-protein-mediated mechanisms, but also through the ubiquitous cellular scaffolds β-arrestin-1 and β-arrestin-2. Previous studies have implicated β-arrestins as regulators of actin reorganization in response to GPCR stimulation while also being required for membrane protrusion events that accompany cellular motility. One of the most critical events in the active movement of cells is the cyclic phosphorylation and activation of myosin light chain (MLC, which is required for cellular contraction and movement. We have identified the myosin light chain phosphatase Targeting Subunit (MYPT-1 as a binding partner of the β-arrestins and found that β-arrestins play a role in regulating the turnover of phosphorylated myosin light chain. In response to stimulation of the angiotensin Type 1a Receptor (AT1aR, MLC phosphorylation is induced quickly and potently. We have found that β-arrestin-2 facilitates dephosphorylation of MLC, while, in a reciprocal fashion, β-arrestin 1 limits dephosphorylation of MLC. Intriguingly, loss of either β-arrestin-1 or 2 blocks phospho-MLC turnover and causes a decrease in the contraction of cells as monitored by atomic force microscopy (AFM. Furthermore, by employing the β-arrestin biased ligand [Sar(1,Ile(4,Ile(8]-Ang, we demonstrate that AT1aR-mediated cellular motility involves a β-arrestin dependent component. This suggests that the reciprocal regulation of MLC phosphorylation status by β-arrestins-1 and 2 causes turnover in the phosphorylation status of MLC that is required for cell contractility and subsequent chemotaxic motility.

  2. Interactions of a potent cyclic peptide inhibitor with the light chain of botulinum neurotoxin A: Insights from X-ray crystallography.

    Science.gov (United States)

    Kumaran, Desigan; Adler, Michael; Levit, Matthew; Krebs, Michael; Sweeney, Richard; Swaminathan, Subramanyam

    2015-11-15

    The seven antigenically distinct serotypes (A-G) of botulinum neurotoxin (BoNT) are responsible for the deadly disease botulism. BoNT serotype A (BoNT/A) exerts its lethal action by cleaving the SNARE protein SNAP-25, leading to inhibition of neurotransmitter release, flaccid paralysis and autonomic dysfunction. BoNTs are dichain proteins consisting of a ∼ 100 kDa heavy chain and a ∼ 50 kDa light chain; the former is responsible for neurospecific binding, internalization and translocation, and the latter for cleavage of neuronal SNARE proteins. Because of their extreme toxicity and history of weaponization, the BoNTs are regarded as potential biowarfare/bioterrorism agents. No post-symptomatic therapeutic interventions are available for BoNT intoxication other than intensive care; therefore it is imperative to develop specific antidotes against this neurotoxin. To this end, a cyclic peptide inhibitor (CPI-1) was evaluated in a FRET assay for its ability to inhibit BoNT/A light chain (Balc). CPI was found to be highly potent, exhibiting a Ki of 12.3 nM with full-length Balc448 and 39.2 nM using a truncated crystallizable form of the light chain (Balc424). Cocrystallization studies revealed that in the Balc424-CPI-1 complex, the inhibitor adopts a helical conformation, occupies a high percentage of the active site cavity and interacts in an amphipathic manner with critical active site residues. The data suggest that CPI-1 prevents SNAP-25 from accessing the Balc active site by blocking both the substrate binding path at the surface and the Zn(2+) binding region involved in catalysis. This differs from linear peptide inhibitors described to date which block only the latter. Published by Elsevier Ltd.

  3. Myosin light chain 2-based selection of human iPSC-derived early ventricular cardiac myocytes.

    Science.gov (United States)

    Bizy, Alexandra; Guerrero-Serna, Guadalupe; Hu, Bin; Ponce-Balbuena, Daniela; Willis, B Cicero; Zarzoso, Manuel; Ramirez, Rafael J; Sener, Michelle F; Mundada, Lakshmi V; Klos, Matthew; Devaney, Eric J; Vikstrom, Karen L; Herron, Todd J; Jalife, José

    2013-11-01

    Applications of human induced pluripotent stem cell derived-cardiac myocytes (hiPSC-CMs) would be strengthened by the ability to generate specific cardiac myocyte (CM) lineages. However, purification of lineage-specific hiPSC-CMs is limited by the lack of cell marking techniques. Here, we have developed an iPSC-CM marking system using recombinant adenoviral reporter constructs with atrial- or ventricular-specific myosin light chain-2 (MLC-2) promoters. MLC-2a and MLC-2v selected hiPSC-CMs were purified by fluorescence-activated cell sorting and their biochemical and electrophysiological phenotypes analyzed. We demonstrate that the phenotype of both populations remained stable in culture and they expressed the expected sarcomeric proteins, gap junction proteins and chamber-specific transcription factors. Compared to MLC-2a cells, MLC-2v selected CMs had larger action potential amplitudes and durations. In addition, by immunofluorescence, we showed that MLC-2 isoform expression can be used to enrich hiPSC-CM consistent with early atrial and ventricular myocyte lineages. However, only the ventricular myosin light chain-2 promoter was able to purify a highly homogeneous population of iPSC-CMs. Using this approach, it is now possible to develop ventricular-specific disease models using iPSC-CMs while atrial-specific iPSC-CM cultures may require additional chamber-specific markers. © 2013.

  4. Quantum information processing with a travelling wave of light

    Science.gov (United States)

    Serikawa, Takahiro; Shiozawa, Yu; Ogawa, Hisashi; Takanashi, Naoto; Takeda, Shuntaro; Yoshikawa, Jun-ichi; Furusawa, Akira

    2018-02-01

    We exploit quantum information processing on a traveling wave of light, expecting emancipation from thermal noise, easy coupling to fiber communication, and potentially high operation speed. Although optical memories are technically challenging, we have an alternative approach to apply multi-step operations on traveling light, that is, continuous-variable one-way computation. So far our achievement includes generation of a one-million-mode entangled chain in time-domain, mode engineering of nonlinear resource states, and real-time nonlinear feedforward. Although they are implemented with free space optics, we are also investigating photonic integration and performed quantum teleportation with a passive liner waveguide chip as a demonstration of entangling, measurement, and feedforward. We also suggest a loop-based architecture as another model of continuous-variable computing.

  5. LONG-TERM LIGHT CURVE OF HIGHLY VARIABLE PROTOSTELLAR STAR GM CEP

    International Nuclear Information System (INIS)

    Xiao Limin; Kroll, Peter; Henden, Arne A.

    2010-01-01

    We present data from the archival plates at Harvard College Observatory and Sonneberg Observatory showing the field of the solar-type pre-main-sequence star GM Cep. A total of 186 magnitudes of GM Cep have been measured on these archival plates, with 176 in blue sensitivity, six in visible, and four in red. We combine our data with data from the literature and from the American Association of Variable Star Observers to depict the long-term light curves of GM Cep in both B and V wavelengths. The light curves span from 1895 until now, with two densely sampled regions (1935-1945 in the B band, and 2006 until now in the V band). The long-term light curves do not show any fast rise behavior as predicted by an accretion mechanism. Both the light curves and the magnitude histograms confirm the conclusion that the light curves are dominated by dips (possibly from extinction) superposed on some quiescence state, instead of outbursts caused by accretion flares. Our result excludes the possibility of GM Cep being a FUor, EXor, or McNeil's Nebula-type star. Several special cases of T Tauri stars were checked, but none of these light curves were compatible with that of GM Cep. The lack of periodicity in the light curve excludes the possibility of GM Cep being a KH 15D system.

  6. Selection of RNA Aptamers Against Botulinum Neurotoxin Type A Light Chain Through a Non-Radioactive Approach.

    Science.gov (United States)

    Chang, Tzuu-Wang; Janardhanan, Pavithra; Mello, Charlene M; Singh, Bal Ram; Cai, Shuowei

    2016-09-01

    Botulinum neurotoxin (BoNT), a category A agent, is the most toxic molecule known to mankind. The endopeptidase activity of light chain domain of BoNT is the cause for the inhibition of the neurotransmitter release and the flaccid paralysis that leads to lethality in botulism. Currently, antidotes are not available to reverse the flaccid paralysis caused by BoNT. In the present study, a non-radioactive-based systematic evolution of ligands by exponential enrichment (SELEX) process is developed by utilizing surface plasmon resonance to monitor the binding enrichment. Two RNA aptamers have been identified as strong binders against light chain of botulinum neurotoxin type A. These two aptamers showed strong inhibition activity on LCA, with IC50 in nanomolar range. Inhibition kinetic studies reveal mid nanomolar KI and non-competitive nature of their inhibition, suggesting that they have strong potential as antidotes that can reverse the symptom caused by BoNT/A. More importantly, we observed that the 2'-fluorine-pyrimidine-modified RNA aptamers identified here do not change their binding and biological activities. This observation could lead to a cost-effective way for SELEX, by using regular nucleotide during SELEX, and 2'-fluorine-pyrimidine-modified nucleotide for final application to enhance their RNase-resistance.

  7. Light-chain amyloidosis presenting with rapidly progressive submucosal hemorrhage of the stomach

    Directory of Open Access Journals (Sweden)

    Song-Yi Kim

    2016-04-01

    Full Text Available The gastrointestinal tract is frequently in involved light-chain (AL amyloidosis, but significant hemorrhagic complications are rare. A 71-year-old man presented to our hospital with dyspepsia and heartburn for 1 month. Gastroscopy revealed a large submucosal hematoma at the gastric fundus. Two days later, a follow-up gastroscopy indicated extensive expansion of the hematoma throughout the upper half of the stomach. The hematoma displayed ongoing expansion during the endoscopic examination, suggesting that rupture was imminent. Emergency total gastrectomy was performed, and amyloidosis was confirmed after examining the surgical specimen. Bone marrow examination revealed multiple myeloma, and serum immunoglobulin assay confirmed the diagnosis of myeloma-associated AL amyloidosis. At manuscript submission, the patient was doing well and was undergoing chemotherapy.

  8. Screens as light biological variable in microgravitational space environment.

    Science.gov (United States)

    Schlacht, S.; Masali, M.

    Foreword The ability of the biological organisms to orient themselves and to synchronize on the variations of the solar rhythms is a fundamental aspect in the planning of the human habitat above all when habitat is confined in the Space the planetary and in satellite outer space settlements In order to simulate the experience of the astronauts in long duration missions one of the dominant characteristics of the Space confined habitats is the absence of the earthlings solar cycles references The Sun is the main references and guidelines of the biological compass and timepiece The organism functions are influenced from the variation of the light in the round of the 24 hours the human circadian rhythms In these habitats it is therefore necessary to reproduce the color and intensity of the solar light variations along the arc of the day according to defined scientific programs assuring a better performance of the human organism subsubsection Multilayer Foldable Screens as biological environmental variable In the project Multilayer Foldable Screens are the monitors posed in the ceiling of an Outer Space habitat and are made of liquid crystals and covered with Kevlar they stand for a modulate and flexible structure for different arrangements and different visions Screens work sout s on all the solar light frequencies and display the images that the subject needs They are characterized from the emission of an environmental light that restores the earthly solar cycle for intensity and color temperature to irradiate

  9. Simultaneously measured pupillary light reflex and heart rate variability in healthy children

    International Nuclear Information System (INIS)

    Daluwatte, C; Yao, G; Miles, J H

    2012-01-01

    We investigated the potential inter-relationship between two measures of autonomic nervous system: pupillary light reflex (PLR) and heart rate variability (HRV), in healthy children of 8–16 years old. PLR was measured at both dark- and light-adapted conditions with various stimulation intensities. Simultaneously measured HRV was obtained in five different PLR testing phases: before PLR test, light-adapted PLR test, dark adaptation, dark-adapted PLR test and after PLR test. The frequency domain HRV parameters measured during the PLR test were significantly different from those measured during rest. Both the regression analysis and factor analysis indicated that PLR and HRV parameters were not correlated, which suggests that they may provide complementary assessment of different aspects of the overall autonomic nervous system. (paper)

  10. Simultaneously measured pupillary light reflex and heart rate variability in healthy children

    Energy Technology Data Exchange (ETDEWEB)

    Daluwatte, C; Yao, G [Department of Biological Engineering, University of Missouri, Columbia, MO 65211 (United States); Miles, J H, E-mail: YaoG@missouri.edu [Child Health and Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, Columbia, MO 65211 (United States)

    2012-06-15

    We investigated the potential inter-relationship between two measures of autonomic nervous system: pupillary light reflex (PLR) and heart rate variability (HRV), in healthy children of 8–16 years old. PLR was measured at both dark- and light-adapted conditions with various stimulation intensities. Simultaneously measured HRV was obtained in five different PLR testing phases: before PLR test, light-adapted PLR test, dark adaptation, dark-adapted PLR test and after PLR test. The frequency domain HRV parameters measured during the PLR test were significantly different from those measured during rest. Both the regression analysis and factor analysis indicated that PLR and HRV parameters were not correlated, which suggests that they may provide complementary assessment of different aspects of the overall autonomic nervous system. (paper)

  11. Quantum hacking on a practical continuous-variable quantum cryptosystem by inserting an external light

    Science.gov (United States)

    Qin, Hao; Kumar, Rupesh; Alleaume, Romain

    2015-10-01

    We report here a new side channel attack on a practical continuous-variable (CV) quantum key distribution (QKD) system. Inspired by blinding attack in discrete-variable QKD, we formalize an attack strategy by inserting an external light into a CV QKD system implemented Gaussian-modulated coherent state protocol and show that our attack can compromise its practical security. In this attack, we concern imperfections of a balanced homodyne detector used in CV QKD. According to our analysis, if one inserts an external light into Bob's signal port, due to the imperfect subtraction from the homodyne detector, the leakage of the external light contributes a displacement on the homodyne signal which causes detector electronics saturation. In consequence, Bob's quadrature measurement is not linear with the quadrature sent by Alice. By considering such vulnerability, a potential Eve can launch a full intercept-resend attack meanwhile she inserts an external light into Bob's signal port. By selecting proper properties of the external light, Eve actively controls the induced displacement value from the inserted light which results saturation of homodyne detection. In consequence, Eve can bias the excess noise due to the intercept-resend attack and the external light, such that Alice and Bob believe their excess noise estimation is below the null key threshold and they can still share a secret key. Our attack shows that the detector loopholes also exist in CV QKD, and it seems influence all the CV QKD systems using homodyne detection, since all the practical detectors have finite detection range.

  12. [The prognostic value of baseline serum free light chain in cardiac amyloidosis].

    Science.gov (United States)

    Zhao, Lei; Tian, Zhuang; Fang, Quan

    2016-03-01

    To analyze the prognostic value of baseline serum free light chain (sFLC) in light-chain (AL) cardiac amyloidosis. Twenty-seven patients with AL cardiac amyloidosis were retrospectively reviewed from January 2014 to January 2015. sFLC was measured by immuoturbidimetric assay. Baseline characteristics, echocardiographic parameters and electrocardiogram data were analyzed. According to the median baseline dFLC (involved sFLC minus uninvolved sFLC), patients were categorized into either the low dFLC(≤ 307 mg/L) or the high dFLC group (>307 mg/L). More subjects in the high dFLC group with early/late diastolic mitral velocity ratio (E/A ratio) over 2 (71.4% vs 30.8%, P=0.035), and subjects in this group had a shorter median survival time than those in the low dFLC group (3 months vs 17 months, P=0.004). A similar phenomenon for median survival time was observed when the subjects were redivided either by a new cut-off value of 180 mg/L for dFLC (low dFLC group: 17 months; high dFLC group: 4 months, P=0.014) or a κ/λ ratio, in which subjects with κ type sFLC-ratio ≤ 19.6 and λ type sFLC-ratio>0.065 were in the low sFLC-ratio group (17 months) and those with κ type sFLC-ratio > 19.6 and λ type sFLC-ratio ≤ 0.065 were in the high sFLC-ratio group (4 months, P=0.023). In multivariate analysis, dFLC and New York Heart Association (NYHA)classification of cardiac function were two risk factors associated with all-cause mortality in patients, among which the hazard ratio for higher dFLC was 4.28 (95%CI 1.55-11.8, P=0.005). The level of sFLC could be a marker for the prognosis of AL cardiac amyloidosis.

  13. Angiotensin II induces reorganization of the actin cytoskeleton and myosin light-chain phosphorylation in podocytes through rho/ROCK-signaling pathway

    NARCIS (Netherlands)

    Wang, Siyuan; Chen, Cheng; Su, Ke; Zha, Dongqing; Liang, Wei; Hillebrands, J L; van Goor, Harry; Ding, Guohua

    2016-01-01

    Aims In the present study, we have evaluated the effect of angiotensin II (Ang II) on actin cytoskeleton reorganization and myosin light-chain (MLC) phosphorylation in podocytes to demonstrate whether the Rho/Rho-associated coiled kinase (ROCK) pathway is involved podocyte injury. Methods Eighteen

  14. Influence of fast and slow alkali myosin light chain isoforms on the kinetics of stretch-induced force transients of fast-twitch type IIA fibres of rat.

    Science.gov (United States)

    Andruchov, Oleg; Galler, Stefan

    2008-03-01

    This study contributes to understand the physiological role of slow myosin light chain isoforms in fast-twitch type IIA fibres of skeletal muscle. These isoforms are often attached to the myosin necks of rat type IIA fibres, whereby the slow alkali myosin light chain isoform MLC1s is much more frequent and abundant than the slow regulatory myosin light chain isoform MLC2s. In the present study, single-skinned rat type IIA fibres were maximally Ca(2+) activated and subjected to stepwise stretches for causing a perturbation of myosin head pulling cycles. From the time course of the resulting force transients, myosin head kinetics was deduced. Fibres containing MLC1s exhibited slower kinetics independently of the presence or absence of MLC2s. At the maximal MLC1s concentration of about 75%, the slowing was about 40%. The slowing effect of MLC1s is possibly due to differences in the myosin heavy chain binding sites of the fast and slow alkali MLC isoforms, which changes the rigidity of the myosin neck. Compared with the impact of myosin heavy chain isoforms in various fast-twitch fibre types, the influence of MLC1s on myosin head kinetics of type IIA fibres is much smaller. In conclusion, the physiological role of fast and slow MLC isoforms in type IIA fibres is a fine-tuning of the myosin head kinetics.

  15. Three-dimensional Speckle Tracking Echocardiography in Light Chain Cardiac Amyloidosis: Examination of Left and Right Ventricular Myocardial Mechanics Parameters.

    Science.gov (United States)

    Urbano-Moral, Jose Angel; Gangadharamurthy, Dakshin; Comenzo, Raymond L; Pandian, Natesa G; Patel, Ayan R

    2015-08-01

    The study of myocardial mechanics has a potential role in the detection of cardiac involvement in patients with amyloidosis. This study aimed to characterize 3-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics in light chain amyloidosis and examine their relationship with brain natriuretic peptide. In patients with light chain amyloidosis, left ventricular longitudinal and circumferential strain (n=40), and right ventricular longitudinal strain and radial displacement (n=26) were obtained by 3-dimensional-speckle tracking echocardiography. Brain natriuretic peptide levels were determined. All myocardial mechanics measurements showed differences when compared by brain natriuretic peptide level tertiles. Left and right ventricular longitudinal strain were highly correlated (r=0.95, P<.001). Left ventricular longitudinal and circumferential strain were reduced in patients with cardiac involvement (-9±4 vs -16±2; P<.001, and -24±6 vs -29±4; P=.01, respectively), with the most prominent impairment at the basal segments. Right ventricular longitudinal strain and radial displacement were diminished in patients with cardiac involvement (-9±3 vs -17±3; P<.001, and 2.7±0.8 vs 3.8±0.3; P=.002). On multivariate analysis, left ventricular longitudinal strain was associated with the presence of cardiac involvement (odds ratio = 1.6; 95% confidence interval, 1.04 to 2.37; P=.03) independent of the presence of brain natriuretic peptide and troponin I criteria for cardiac amyloidosis. Three-dimensional-speckle tracking echocardiography-derived left and right ventricular myocardial mechanics are increasingly altered as brain natriuretic peptide increases in light chain amyloidosis. There appears to be a strong association between left ventricular longitudinal strain and cardiac involvement, beyond biomarkers such as brain natriuretic peptide and troponin I. Copyright © 2015 Sociedad Española de Cardiología. Published by

  16. Imaging Variable Stars with HST

    Science.gov (United States)

    Karovska, M.

    2012-06-01

    (Abstract only) The Hubble Space Telescope (HST) observations of astronomical sources, ranging from objects in our solar system to objects in the early Universe, have revolutionized our knowledge of the Universe its origins and contents. I highlight results from HST observations of variable stars obtained during the past twenty or so years. Multiwavelength observations of numerous variable stars and stellar systems were obtained using the superb HST imaging capabilities and its unprecedented angular resolution, especially in the UV and optical. The HST provided the first detailed images probing the structure of variable stars including their atmospheres and circumstellar environments. AAVSO observations and light curves have been critical for scheduling of many of these observations and provided important information and context for understanding of the imaging results of many variable sources. I describe the scientific results from the imaging observations of variable stars including AGBs, Miras, Cepheids, semiregular variables (including supergiants and giants), YSOs and interacting stellar systems with a variable stellar components. These results have led to an unprecedented understanding of the spatial and temporal characteristics of these objects and their place in the stellar evolutionary chains, and in the larger context of the dynamic evolving Universe.

  17. THE LICK AGN MONITORING PROJECT: PHOTOMETRIC LIGHT CURVES AND OPTICAL VARIABILITY CHARACTERISTICS

    International Nuclear Information System (INIS)

    Walsh, Jonelle L.; Bentz, Misty C.; Barth, Aaron J.; Minezaki, Takeo; Sakata, Yu; Yoshii, Yuzuru; Baliber, Nairn; Bennert, Vardha Nicola; Street, Rachel A.; Treu, Tommaso; Li Weidong; Filippenko, Alexei V.; Stern, Daniel; Brown, Timothy M.; Canalizo, Gabriela; Gates, Elinor L.; Greene, Jenny E.; Malkan, Matthew A.; Woo, Jong-Hak

    2009-01-01

    The Lick AGN Monitoring Project targeted 13 nearby Seyfert 1 galaxies with the intent of measuring the masses of their central black holes using reverberation mapping. The sample includes 12 galaxies selected to have black holes with masses roughly in the range 10 6 -10 7 M sun , as well as the well-studied active galactic nucleus (AGN) NGC 5548. In conjunction with a spectroscopic monitoring campaign, we obtained broadband B and V images on most nights from 2008 February through 2008 May. The imaging observations were carried out by four telescopes: the 0.76 m Katzman Automatic Imaging Telescope, the 2 m Multicolor Active Galactic Nuclei Monitoring telescope, the Palomar 60 inch (1.5 m) telescope, and the 0.80 m Tenagra II telescope. Having well-sampled light curves over the course of a few months is useful for obtaining the broad-line reverberation lag and black hole mass, and also allows us to examine the characteristics of the continuum variability. In this paper, we discuss the observational methods and the photometric measurements, and present the AGN continuum light curves. We measure various variability characteristics of each of the light curves. We do not detect any evidence for a time lag between the B- and V-band variations, and we do not find significant color variations for the AGNs in our sample.

  18. Alignment-free Transcriptomic and Metatranscriptomic Comparison Using Sequencing Signatures with Variable Length Markov Chains.

    Science.gov (United States)

    Liao, Weinan; Ren, Jie; Wang, Kun; Wang, Shun; Zeng, Feng; Wang, Ying; Sun, Fengzhu

    2016-11-23

    The comparison between microbial sequencing data is critical to understand the dynamics of microbial communities. The alignment-based tools analyzing metagenomic datasets require reference sequences and read alignments. The available alignment-free dissimilarity approaches model the background sequences with Fixed Order Markov Chain (FOMC) yielding promising results for the comparison of microbial communities. However, in FOMC, the number of parameters grows exponentially with the increase of the order of Markov Chain (MC). Under a fixed high order of MC, the parameters might not be accurately estimated owing to the limitation of sequencing depth. In our study, we investigate an alternative to FOMC to model background sequences with the data-driven Variable Length Markov Chain (VLMC) in metatranscriptomic data. The VLMC originally designed for long sequences was extended to apply to high-throughput sequencing reads and the strategies to estimate the corresponding parameters were developed. The flexible number of parameters in VLMC avoids estimating the vast number of parameters of high-order MC under limited sequencing depth. Different from the manual selection in FOMC, VLMC determines the MC order adaptively. Several beta diversity measures based on VLMC were applied to compare the bacterial RNA-Seq and metatranscriptomic datasets. Experiments show that VLMC outperforms FOMC to model the background sequences in transcriptomic and metatranscriptomic samples. A software pipeline is available at https://d2vlmc.codeplex.com.

  19. Assessment of Light Environment Variability in Broadleaved Forest Canopies Using Terrestrial Laser Scanning

    Directory of Open Access Journals (Sweden)

    Dimitry Van der Zande

    2010-06-01

    Full Text Available Light availability inside a forest canopy is of key importance to many ecosystem processes, such as photosynthesis and transpiration. Assessment of light availability and within-canopy light variability enables a more detailed understanding of these biophysical processes. The changing light-vegetation interaction in a homogeneous oak (Quercus robur L. stand was studied at different moments during the growth season using terrestrial laser scanning datasets and ray tracing technology. Three field campaigns were organized at regular time intervals (24 April 2008; 07 May 2008; 23 May 2008 to monitor the increase of foliage material. The laser scanning data was used to generate 3D representations of the forest stands, enabling structure feature extraction and light interception modeling, using the Voxel-Based Light Interception Model (VLIM. The VLIM is capable of estimating the relative light intensity or Percentage of Above Canopy Light (PACL at any arbitrary point in the modeled crown space. This resulted in a detailed description of the dynamic light environments inside the canopy. Mean vertical light extinction profiles were calculated for the three time frames, showing significant differences in light attenuation by the canopy between April 24 on the one hand, and May 7 and May 23 on the other hand. The proposed methodology created the opportunity to link these within-canopy light distributions to the increasing amount of photosynthetically active leaf material and its distribution in the considered 3D space.

  20. Mouse myeloma cells that make short immunoglobulin heavy chains: pleiotropic effects on glycosylation and chain assembly

    OpenAIRE

    1984-01-01

    Two variants in immunoglobulin heavy chain production, derived from the MPC 11 mouse myeloma cell line, make short heavy (H) chains with identical precise deletions of the CH3 domain. The CH3 domain is expressed in the H chain mRNA from both variants. Although in vitro translation of this mRNA produces one H chain species, deleted heavy chains are secreted as heavy-light (HL) and H2L2 moieties in contrast to MPC 11, which secretes only H2L2 . The heavy chains of HL apparently contain more car...

  1. Vascular O-GlcNAcylation augments reactivity to constrictor stimuli by prolonging phosphorylated levels of the myosin light chain

    Energy Technology Data Exchange (ETDEWEB)

    Lima, V.V. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil); Lobato, N.S.; Filgueira, F.P. [Curso de Medicina, Setor de Fisiologia Humana, Universidade Federal de Goiás, Jataí, GO (Brazil); Webb, R.C. [Department of Physiology, Georgia Regents University, Augusta, GA (United States); Tostes, R.C. [Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP (Brazil); Giachini, F.R. [Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Mato Grosso, Barra do Garças, MT (Brazil)

    2014-08-15

    O-GlcNAcylation is a modification that alters the function of numerous proteins. We hypothesized that augmented O-GlcNAcylation levels enhance myosin light chain kinase (MLCK) and reduce myosin light chain phosphatase (MLCP) activity, leading to increased vascular contractile responsiveness. The vascular responses were measured by isometric force displacement. Thoracic aorta and vascular smooth muscle cells (VSMCs) from rats were incubated with vehicle or with PugNAc, which increases O-GlcNAcylation. In addition, we determined whether proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation. PugNAc enhanced phenylephrine (PE) responses in rat aortas (maximal effect, 14.2±2 vs 7.9±1 mN for vehicle, n=7). Treatment with an MLCP inhibitor (calyculin A) augmented vascular responses to PE (13.4±2 mN) and abolished the differences in PE-response between the groups. The effect of PugNAc was not observed when vessels were preincubated with ML-9, an MLCK inhibitor (7.3±2 vs 7.5±2 mN for vehicle, n=5). Furthermore, our data showed that differences in the PE-induced contractile response between the groups were abolished by the activator of AMP-activated protein kinase (AICAR; 6.1±2 vs 7.4±2 mN for vehicle, n=5). PugNAc increased phosphorylation of myosin phosphatase target subunit 1 (MYPT-1) and protein kinase C-potentiated inhibitor protein of 17 kDa (CPI-17), which are involved in RhoA/Rho-kinase-mediated inhibition of myosin phosphatase activity. PugNAc incubation produced a time-dependent increase in vascular phosphorylation of myosin light chain and decreased phosphorylation levels of AMP-activated protein kinase, which decreased the affinity of MLCK for Ca{sup 2+}/calmodulin. Our data suggest that proteins that play an important role in the regulation of MLCK and MLCP activity are directly affected by O-GlcNAcylation, favoring vascular contraction.

  2. Opinion: the red-light response of stomatal movement is sensed by the redox state of the photosynthetic electron transport chain.

    Science.gov (United States)

    Busch, Florian A

    2014-02-01

    Guard cells regulate CO2 uptake and water loss of a leaf by controlling stomatal movement in response to environmental factors such as CO2, humidity, and light. The mechanisms by which stomata respond to red light are actively debated in the literature, and even after decades of research it is still controversial whether stomatal movement is related to photosynthesis or not. This review summarizes the current knowledge of the red-light response of stomata. A comparison of published evidence suggests that stomatal movement is controlled by the redox state of photosynthetic electron transport chain components, in particular the redox state of plastoquinone. Potential consequences for the modeling of stomatal conductance are discussed.

  3. Synergy between the Multiple Supply Chain and Green Supply Chain Management (GSCM) approaches: an initial analysis aimed at fostering supply chain sustainability

    OpenAIRE

    Ana Lima de Carvalho; Livia Rodrigues Ignácio; Kleber Francisco Esposto; Aldo Roberto Ometto

    2016-01-01

    The concept of Green Supply Chain Management (GSCM) was created in the 90s to reduce the environmental impacts of productive systems. This approach seeks to improve the environmental performance of all the participants in a supply chain, from the extraction of raw materials to the use and final disposal of the product, through relationships of collaboration or conformity between the parties. The multiple supply chains approach established by Gattorna (2009) brought to light different supply c...

  4. Anemia crônica e glomerulopatia secundárias à Doença de Depósito das Cadeias Leves Chronic anemia and glomerulopathy secondary to Light-chain Deposition Disease

    Directory of Open Access Journals (Sweden)

    Ítala P. Silveira

    2004-01-01

    Full Text Available Os autores relatam o caso de uma paciente do sexo feminino, 65 anos de idade, internada com anemia de longa evolução que se associou posteriormente a uma glomerulopatia manifestada por proteinúria, cilindrúria e perda de função renal. As cadeias leves no plasma e na urina estavam elevadas, sobretudo a fração kappa e uma biópsia renal estudada por imunofluorescência e microscopia eletrônica confirmou o diagnóstico de Doença de Depósito das Cadeias Leves. A nefropatia de cadeia leve ocorre pela superprodução de cadeia leve de imunoglobulina produzida por linfócitos B com deposição nas membranas tubulares e no glomérulo.The authors present a case of a 65-year-old female patient, with chronic anemia associated with glomerulopathy manifested as proteinuria, cylindruria and renal failure. There were high serum and urinary levels of light chains and the diagnosis was performed by renal biopsy, examined using immunofluorescence and by electron microscopy that showed light chain paraproteins. Nephropathy of light-chain deposition disease occurs due to an over-production of light chains from immunoglobulins produced by B lymphocytes with a deposit in tubular and glomerular membranes.

  5. Precast Pearl-Chain concrete arch bridges

    DEFF Research Database (Denmark)

    Halding, Philip Skov; Hertz, Kristian Dahl; Schmidt, Jacob Wittrup

    2015-01-01

    A Pearl-Chain Bridge is a closed-spandrel arch bridge consisting of a number of straight pre-fabricated so called Super-Light Deck elements put together in an arch shape by post-tensioning cables. Several Pearl-Chain arches can be positioned adjacent to each other by a crane to achieve a bridge...... of a desired width. On top of the arch is a filling material to level out the surface of the above road. The filling only transfers vertical loads to the arch. The geometry and material properties of Super-Light Decks are presented, and we refer to several fullscale tests of Pearl-Chain arches where...... the technology was used. We also study other important components and details in the Pearl-Chain Bridge concept and review the effects of different types of loads. A theoretical case study of a circular 30 m span Pearl-Chain Bridge is presented showing the influence of a number of parameters: The number of post...

  6. Intestinal infection with Giardia spp. reduces epithelial barrier function in a myosin light chain kinase-dependent fashion.

    Science.gov (United States)

    Scott, Kevin G-E; Meddings, Jonathon B; Kirk, David R; Lees-Miller, Susan P; Buret, André G

    2002-10-01

    Giardiasis causes malabsorptive diarrhea, and symptoms can be present in the absence of any significant morphologic injury to the intestinal mucosa. The effects of giardiasis on epithelial permeability in vivo remain unknown, and the role of T cells and myosin light chain kinase (MLCK) in altered intestinal barrier function is unclear. This study was conducted to determine whether Giardia spp. alters intestinal permeability in vivo, to assess whether these abnormalities are dependent on T cells, and to assess the role of MLCK in altered epithelial barrier function. Immunocompetent and isogenic athymic mice were inoculated with axenic Giardia muris trophozoites or sterile vehicle (control), then assessed for trophozoite colonization and gastrointestinal permeability. Mechanistic studies using nontransformed human duodenal epithelial monolayers (SCBN) determined the effects of Giardia on myosin light chain (MLC) phosphorylation, transepithelial fluorescein isothiocyanate-dextran fluxes, cytoskeletal F-actin, tight junctional zonula occludens-1 (ZO-1), and MLCK. Giardia infection caused a significant increase in small intestinal, but not gastric or colonic, permeability that correlated with trophozoite colonization in both immunocompetent and athymic mice. In vitro, Giardia increased permeability and phosphorylation of MLC and reorganized F-actin and ZO-1. These alterations were abolished with an MLCK inhibitor. Disruption of small intestinal barrier function is T cell independent, disappears on parasite clearance, and correlates with reorganization of cytoskeletal F-actin and tight junctional ZO-1 in an MLCK-dependent fashion.

  7. Myosin light chain kinase knockout improves gut barrier function and confers a survival advantage in polymicrobial sepsis.

    Science.gov (United States)

    Lorentz, C Adam; Liang, Zhe; Meng, Mei; Chen, Ching-Wen; Yoseph, Benyam P; Breed, Elise R; Mittal, Rohit; Klingensmith, Nathan J; Farris, Alton B; Burd, Eileen M; Koval, Michael; Ford, Mandy L; Coopersmith, Craig M

    2017-06-07

    Sepsis-induced intestinal hyperpermeability is mediated by disruption of the epithelial tight junction, which is closely associated with the peri-junctional actin-myosin ring. Myosin light chain kinase (MLCK) phosphorylates the myosin regulatory light chain, resulting in increased permeability. The purpose of this study was to determine whether genetic deletion of MLCK would alter gut barrier function and survival from sepsis. MLCK -/- and wild type (WT) mice were subjected to cecal ligation and puncture and assayed for both survival and mechanistic studies. Survival was significantly increased in MLCK -/- mice (95% vs. 24%, p<0.0001). Intestinal permeability increased in septic WT mice compared to unmanipulated mice. In contrast, permeability in septic MLCK -/- mice was similar to that seen in unmanipulated animals. Improved gut barrier function in MLCK -/- mice was associated with increases in the tight junction mediators ZO-1 and claudin 15 without alterations in claudin 1, 2, 3, 4, 5, 7, 8, 13, occludin or JAM-A. Other components of intestinal integrity (apoptosis, proliferation and villus length) were unaffected by MLCK deletion as were local peritoneal inflammation and distant lung injury. Systemic IL-10 was decreased greater than 10-fold in MLCK -/- mice; however, survival was similar between septic MLCK -/- mice given exogenous IL-10 or vehicle. These data demonstrate that deletion of MLCK improves survival following sepsis, associated with normalization of intestinal permeability and selected tight junction proteins.

  8. A residue-specific shift in stability and amyloidogenicity of antibody variable domains.

    Science.gov (United States)

    Nokwe, Cardine N; Zacharias, Martin; Yagi, Hisashi; Hora, Manuel; Reif, Bernd; Goto, Yuji; Buchner, Johannes

    2014-09-26

    Variable (V) domains of antibodies are essential for antigen recognition by our adaptive immune system. However, some variants of the light chain V domains (VL) form pathogenic amyloid fibrils in patients. It is so far unclear which residues play a key role in governing these processes. Here, we show that the conserved residue 2 of VL domains is crucial for controlling its thermodynamic stability and fibril formation. Hydrophobic side chains at position 2 stabilize the domain, whereas charged residues destabilize and lead to amyloid fibril formation. NMR experiments identified several segments within the core of the VL domain to be affected by changes in residue 2. Furthermore, molecular dynamic simulations showed that hydrophobic side chains at position 2 remain buried in a hydrophobic pocket, and charged side chains show a high flexibility. This results in a predicted difference in the dissociation free energy of ∼10 kJ mol(-1), which is in excellent agreement with our experimental values. Interestingly, this switch point is found only in VL domains of the κ family and not in VLλ or in VH domains, despite a highly similar domain architecture. Our results reveal novel insight into the architecture of variable domains and the prerequisites for formation of amyloid fibrils. This might also contribute to the rational design of stable variable antibody domains. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  9. Characteristics and Long-Term Outcome of Patients with Systemic Immunoglobulin Light-Chain Amyloidosis

    DEFF Research Database (Denmark)

    Nelson, Lærke Marie; Gustafsson, Finn; Gimsing, Peter

    2015-01-01

    Background/Aims: Immunoglobulin light-chain (AL) amyloidosis is a systemic disorder that causes progressive organ dysfunction. The optimal treatment strategy requires accurate patient stratification with an emphasis on the extent of cardiac involvement. Reports on its prognosis are sparse...... and predominantly originate from highly selected centers. We aimed to evaluate patient characteristics and outcomes in a cohort treated at a single center. Methods: This is a single-center retrospective study of 63 consecutive patients diagnosed with AL amyloidosis between January 2000 and December 2012. Patients...... were evaluated by treatment strategy and cardiac involvement. Results: The mean age at diagnosis was 61.4 years (±8.9), and 39 patients (62%) were male. Thirty-two (51%) patients presented with cardiac amyloid involvement (CA) and the remaining 31 (49%) had noncardiac amyloidosis (NCA). The median...

  10. Serum levels of immunoglobulin free light chains in patients with chronic hepatitis C presenting cryoglobulinemia

    Directory of Open Access Journals (Sweden)

    Isabela S. Oliveira

    2014-11-01

    Full Text Available Hepatitis C virus (HCV infects B-lymphocytes, provokes cellular dysfunction and causes lymphoproliferative diseases such as cryoglobulinemia and non-Hodgkin's B-cell lymphoma. In the present study, we investigated the serum levels of kappa and lambda free light chains (FLC of immunoglobulins and the kappa/lambda FLC ratio in Brazilian patients with chronic HCV infection and cryoglobulinemia. We also analyzed the immunochemical composition of the cryoglobulins in these patients. Twenty-eight cryoglobulinemic HCV patients composed the target group, while 37 HCV patients without cryoglobulinemia were included as controls. The median levels of kappa and lambda FLC were higher in patients with cryoglobulinemia compared to controls (p = 0.001 and p = 0.003, respectively, but the kappa/lambda FLC ratio was similar in patients with and without cryoglobulinemia (p > 0.05. The median FLC ratio was higher in HCV patients presenting with advanced fibrosis of the liver compared to HCV patients without fibrosis (p = 0.004. Kappa and lambda FLC levels were strongly correlated with the IgA, IgG and IgM levels in the patients with cryoglobulinemia. In patients without cryoglobulinemia, the kappa FLC level was only correlated with the IgG level, whereas the lambda FLC were weakly correlated with the IgA, IgG and IgM levels. An immunochemical pattern of mixed cryoglobulins (MC, predominantly IgM, IgG, IgA and kappa light chain, was verified in these immune complexes. We concluded that HCV-infected patients presenting cryoglobulinemia have vigorous polyclonal B-lymphocyte activation due to chronic HCV infection and persistent immune stimulation.

  11. Chain-loaded variable resistance warm-up improves free-weight maximal back squat performance.

    Science.gov (United States)

    Mina, Minas A; Blazevich, Anthony J; Giakas, Giannis; Seitz, Laurent B; Kay, Anthony D

    2016-11-01

    The acute influence of chain-loaded variable resistance exercise on subsequent free-weight one-repetition maximum (1-RM) back squat performance was examined in 16 recreationally active men. The participants performed either a free-weight resistance (FWR) or chain-loaded resistance (CLR) back squat warm-up at 85% 1-RM on two separate occasions. After a 5-min rest, the participants attempted a free-weight 1-RM back squat; if successful, subsequent 5% load additions were made until participants failed to complete the lift. During the 1-RM trials, 3D knee joint kinematics and knee extensor and flexor electromyograms (EMG) were recorded simultaneously. Significantly greater 1-RM (6.2 ± 5.0%; p  .05) was found in concentric EMG, eccentric or concentric knee angular velocity, or peak knee flexion angle. Performing a CLR warm-up enhanced subsequent free-weight 1-RM performance without changes in knee flexion angle or eccentric and concentric knee angular velocities; thus a real 1-RM increase was achieved as the mechanics of the lift were not altered. These results are indicative of a potentiating effect of CLR in a warm-up, which may benefit athletes in tasks where high-level strength is required.

  12. Supply Chain Management In Construction Revealed

    OpenAIRE

    Dr. Ghaith Al-Werikat

    2017-01-01

    The construction supply chain plays a major role in the construction market competition. Construction supply chain management assists enterprises by helping to improve competitiveness increase profits and have more control over the different factors and variables within the project. This paper discusses the construction supply chain characteristics challenges and problems supply chains encounter and the benefits of an integrated supply chain in the construction sector.

  13. Quenching Capabilities of Long-Chain Carotenoids in Light-Harvesting-2 Complexes from Rhodobacter sphaeroides with an Engineered Carotenoid Synthesis Pathway.

    Science.gov (United States)

    Dilbeck, Preston L; Tang, Qun; Mothersole, David J; Martin, Elizabeth C; Hunter, C Neil; Bocian, David F; Holten, Dewey; Niedzwiedzki, Dariusz M

    2016-06-23

    Six light-harvesting-2 complexes (LH2) from genetically modified strains of the purple photosynthetic bacterium Rhodobacter (Rb.) sphaeroides were studied using static and ultrafast optical methods and resonance Raman spectroscopy. These strains were engineered to incorporate carotenoids for which the number of conjugated groups (N = NC═C + NC═O) varies from 9 to 15. The Rb. sphaeroides strains incorporate their native carotenoids spheroidene (N = 10) and spheroidenone (N = 11), as well as longer-chain analogues including spirilloxanthin (N = 13) and diketospirilloxantion (N = 15) normally found in Rhodospirillum rubrum. Measurements of the properties of the carotenoid first singlet excited state (S1) in antennas from the Rb. sphaeroides set show that carotenoid-bacteriochlorophyll a (BChl a) interactions are similar to those in LH2 complexes from various other bacterial species and thus are not significantly impacted by differences in polypeptide composition. Instead, variations in carotenoid-to-BChl a energy transfer are primarily regulated by the N-determined energy of the carotenoid S1 excited state, which for long-chain (N ≥ 13) carotenoids is not involved in energy transfer. Furthermore, the role of the long-chain carotenoids switches from a light-harvesting supporter (via energy transfer to BChl a) to a quencher of the BChl a S1 excited state B850*. This quenching is manifested as a substantial (∼2-fold) reduction of the B850* lifetime and the B850* fluorescence quantum yield for LH2 housing the longest carotenoids.

  14. Long-term reversibility of renal dysfunction associated to light chain deposition disease with bortezomib and dexamethasone and high dose therapy and autologous stem cell transplantation

    Directory of Open Access Journals (Sweden)

    Tomás J. González-López

    2011-11-01

    Full Text Available A 63-year-old woman presented with progressive renal insufficiency, until a glomerular filtration rate (GFR of 12 mL/min. A renal biopsy demonstrated glomerular deposition of immunoglobulin k light chain. The presence of a small population of monoclonal plasmacytes producing an only light k monoclonal component was demonstrated and Bortezomib and Dexamethasone (BD was provided as initial therapy. After seven courses of therapy, renal function improved without dialysis requirements up to a GFR 31 mL/min. Under hematological complete response (HCR the patient underwent high dose of melphalan (HDM and autologous peripheral blood stem cell transplant. Fifty-four months later the patient remains in HCR and the GFR has progressively improved up to 48 mL/min. This report describes a notably renal function improvement in a patient with Light Chain Deposition Disease after therapy with BD followed by HDM, which can support this treatment as a future option for these patients.

  15. Force decay evaluation of thermoplastic and thermoset elastomeric chains: A mechanical design comparison.

    Science.gov (United States)

    Masoud, Ahmed I; Tsay, T Peter; BeGole, Ellen; Bedran-Russo, Ana K

    2014-11-01

    To compare the following over a period of 8 weeks: (1) force decay between thermoplastic (TP) and thermoset (TS) elastomeric chains; (2) force decay between light (200-g) and heavy (350-g) initial forces; and (3) force decay between direct chains and chain loops (stretched from one pin around the second pin and back to the first pin). TP and TS chains were obtained from American Orthodontics™ (AOTP, AOTS) and ORMCO™ (OrTP, OrTS). Each of the four chain groups was subdivided into four subgroups with 10 specimens per subgroup: (1) direct chains light force, (2) direct chains heavy force, (3) chain loops light force, and (4) chain loops heavy force. The experiment was performed in artificial saliva (pH of 6.75) at 37°C. A significant difference was found between TP and TS chains, with an average mean difference of around 20% more force decay found in the TP chains (P < .001, α  =  .05). There was no significant difference between direct chains and chain loops except in OrTP, in which direct chains showed more force decay. There was also no significant difference in force decay identified when using light vs heavy forces. TS chains decayed less than TP chains, and chain loop retraction was beneficial only when using OrTP chains. Contrary to the interchangeable use of TP and TS chains in the published literature and in clinical practice, this study demonstrates that they perform differently under stress and that a clear distinction should be made between the two.

  16. Human amyloidogenic light chain proteins result in cardiac dysfunction, cell death, and early mortality in zebrafish.

    Science.gov (United States)

    Mishra, Shikha; Guan, Jian; Plovie, Eva; Seldin, David C; Connors, Lawreen H; Merlini, Giampaolo; Falk, Rodney H; MacRae, Calum A; Liao, Ronglih

    2013-07-01

    Systemic amyloid light-chain (AL) amyloidosis is associated with rapidly progressive and fatal cardiomyopathy resulting from the direct cardiotoxic effects of circulating AL light chain (AL-LC) proteins and the indirect effects of AL fibril tissue infiltration. Cardiac amyloidosis is resistant to standard heart failure therapies, and, to date, there are limited treatment options for these patients. The mechanisms underlying the development of cardiac amyloidosis and AL-LC cardiotoxicity are largely unknown, and their study has been limited by the lack of a suitable in vivo model system. Here, we establish an in vivo zebrafish model of human AL-LC-induced cardiotoxicity. AL-LC isolated from AL cardiomyopathy patients or control nonamyloidogenic LC protein isolated from multiple myeloma patients (Con-LC) was directly injected into the circulation of zebrafish at 48 h postfertilization. AL-LC injection resulted in impaired cardiac function, pericardial edema, and increased cell death relative to Con-LC, culminating in compromised survival with 100% mortality within 2 wk, independent of AL fibril deposition. Prior work has implicated noncanonical p38 MAPK activation in the pathogenesis of AL-LC-induced cardiotoxicity, and p38 MAPK inhibition via SB-203580 rescued AL-LC-induced cardiac dysfunction and cell death and attenuated mortality in zebrafish. This in vivo zebrafish model of AL-LC cardiotoxicity demonstrates that antagonism of p38 MAPK within the AL-LC cardiotoxic signaling response may serve to improve cardiac function and mortality in AL cardiomyopathy. Furthermore, this in vivo model system will allow for further study of the molecular underpinnings of AL cardiotoxicity and identification of novel therapeutic strategies.

  17. The Kinetics of Myosin Light Chain Kinase Activation of Smooth Muscle Myosin in an In Vitro Model System

    OpenAIRE

    Hong, Feng; Facemyer, Kevin C.; Carter, Michael S.; Jackson, Del R.; Haldeman, Brian D.; Ruana, Nick; Sutherland, Cindy; Walsh, Michael P.; Cremo, Christine R.; Baker, Josh E.

    2013-01-01

    During activation of smooth muscle contraction, one myosin light chain kinase (MLCK) molecule rapidly phosphorylates many smooth muscle myosin (SMM) molecules, suggesting that muscle activation rates are influenced by the kinetics of MLCK-SMM interactions. To determine the rate-limiting step underlying activation of SMM by MLCK, we measured the kinetics of calcium-calmodulin (Ca2+-CaM)-MLCK-mediated SMM phosphorylation and the corresponding initiation of SMM-based F-actin motility in an in vi...

  18. Development of an Indirect Competitive Enzyme-Linked Immunosorbent Assay for Glycocholic Acid Based on Chicken Single-Chain Variable Fragment Antibodies.

    Science.gov (United States)

    Cui, Xiping; Vasylieva, Natalia; Wu, Panpan; Barnych, Bogdan; Yang, Jun; Shen, Ding; He, Qiyi; Gee, Shirley J; Zhao, Suqing; Hammock, Bruce D

    2017-10-17

    Glycocholic acid (GCA) is an important metabolite of bile acids, whose urine levels are expected to be a specific diagnostic biomarker for hepatocellular carcinoma (HCC). A high-throughput immunoassay for determination of GCA would be of significant advantage and useful for primary diagnosis, surveillance, and early detection of HCC. Single-chain variable fragment (scFv) antibodies have several desirable characteristics and are an attractive alternative to traditional antibodies for the immunoassay. Because chicken antibodies possess single heavy and light variable functional domains, they are an ideal framework for simplified generation of recombinant antibodies for GCA detection. However, chicken scFvs have rarely been used to detect GCA. In this study, a scFv library was generated from chickens immunized with a GCA hapten coupled to bovine serum albumin (BSA), and anti-GCA scFvs were isolated by a phage-displayed method. Compared to the homologous coating antigen, use of a heterologous coating antigen resulted in about an 85-fold improvement in sensitivity of the immunoassay. This assay, under optimized conditions, had a linear range of 0.02-0.18 μg/mL, with an IC 50 of 0.06 μg/mL. The assay showed negligible cross-reactivity with various related bile acids, except for taurocholic acid. The detection of GCA from spiked human urine samples ranged from 86.7% to 123.3%. These results, combined with the advantages of scFv antibodies, indicated that a chicken scFv-based enzyme-linked immunosorbent assay is a suitable method for high-throughput screening of GCA in human urine.

  19. Supply Chain Management In Construction Revealed

    Directory of Open Access Journals (Sweden)

    Dr. Ghaith Al-Werikat

    2017-03-01

    Full Text Available The construction supply chain plays a major role in the construction market competition. Construction supply chain management assists enterprises by helping to improve competitiveness increase profits and have more control over the different factors and variables within the project. This paper discusses the construction supply chain characteristics challenges and problems supply chains encounter and the benefits of an integrated supply chain in the construction sector.

  20. IgD multiple myeloma: Clinical, biological features and prognostic value of the serum free light chain assay.

    Science.gov (United States)

    Djidjik, R; Lounici, Y; Chergeulaïne, K; Berkouk, Y; Mouhoub, S; Chaib, S; Belhani, M; Ghaffor, M

    2015-09-01

    IgD multiple myeloma (MM) is a rare subtype of myeloma, it affects less than 2% of patients with MM. To evaluate the clinical and prognostic attributes of serum free light chains (sFLCs) analysis, we examined 17 cases of IgD MM. From 1998 to 2012, we obtained 1250 monoclonal gammapathies including 590 multiple myeloma and 17 patients had IgD MM. With preponderance of men patients with a mean age at diagnosis of: 59±12years. Patients with IgD MM have a short survival (Median survival=9months). The presenting features included: bone pain (75%), lymphadenopathy (16%), hepatomegaly (25%), splenomegaly (8%), associated AL amyloidosis (6%), renal impairment function (82%), infections (47%), hypercalcemia (37%) and anemia (93%). Serum electrophoresis showed a subtle M-spike (Mean=13.22±10g/L) in all patients associated to a hypogammaglobulinemia. There was an over-representation of Lambda light chain (65%); high serum β2-microglobulin in 91% and Bence Jones proteinuria was identified in 71%. The median rate of sFLCs κ was 19.05mg/L and 296.75mg/L for sFLCs λ. sFLCR was abnormal in 93% of patients and it showed concordance between baseline sFLCR and the survival (P=0.034). The contribution of FLC assay is crucial for the prognosis of patients with IgD MM. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  1. Prognostic Value of Serum Free Light Chain in Multiple Myeloma.

    Science.gov (United States)

    El Naggar, Amel A; El-Naggar, Mostafa; Mokhamer, El-Hassan; Avad, Mona W

    2015-01-01

    The measurement of serum free light chain (sFLC) has been shown to be valuable in screening for the presence of plasma cell dyscrasia as well as for baseline prognosis in newly diagnosed patients. The aim of the present work was to study the prognostic value of sFLC in multiple myeloma in relation to other serum biomarkers, response to therapy and survival. Forty five newly diagnosed patients with MM were included in the study. Patients were divided into responders and non-responders groups according to response to therapy. sFLC and serum Amyloid A (SAA) were measured by immunonephelometry. The non-responders group showed a statistically significant higher kappa/lambda or lambda/kappa ratio and higher β2 microglobulin level, but lower albumin level at presentation, as compared to the responders group (P < 0.001). However, no statistically significant difference was detected between the two groups regarding SA A or calcium levels. Comparison between sFLC ratio obtained before and after therapy revealed significant decrease after treatment in the responders group (P = 0.05). Survival was significantly inferior in patients with an FLC ratio of ≥ 2.6 or ≤ 0.56 compared with those with an FLC ratio that was between 0.56 and 2.6 (P = 0.002).

  2. Light-chain residue 95 is critical for antigen binding and multispecificity of monoclonal antibody G2.

    Science.gov (United States)

    Usui, Daiki; Inaba, Satomi; Kamatari, Yuji O; Ishiguro, Naotaka; Oda, Masayuki

    2017-09-02

    The monoclonal antibody, G2, specifically binds to the immunogen peptide derived from the chicken prion protein, Pep18mer, and two chicken proteins derived peptides, Pep8 and Pep395; G2 binds with equal affinity to Pep18mer. The amino acid sequences of the three peptides are completely different, and so the recognition mechanism of G2 is unique and interesting. We generated a single-chain Fv (scFv) antibody of G2, and demonstrated its correct folding with an antigen binding function similar to intact G2 antibody. We also generated a Pro containing mutant of G2 scFv at residue 95 of the light chain, and analyzed its antigen binding using a surface plasmon biosensor. The mutant lost its binding ability to Pep18mer, but remained those to Pep8 and Pep395. The results clearly indicate residue 95 as being critical for multispecific antigen binding of G2 at the site generated from the junctional diversity introduced at the joints between the V and J gene segments. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Immunoglobulin diversification in B cell malignancies: internal splicing of heavy chain variable region as a by-product of somatic hypermutation

    NARCIS (Netherlands)

    Bende, R. J.; Aarts, W. M.; Pals, S. T.; van Noesel, C. J. M.

    2002-01-01

    In this study we describe alternative splicing of somatically mutated immunoglobulin (Ig) variable heavy chain (V-H) genes in three distinct primary B cell non-Hodgkin's lymphomas (B-NHL). In two V4-34 expressing lymphomas, ie a post-germinal center type B cell chronic lymphocytic leukemia (B-CLL)

  4. Optical anisotropy of polyimide and polymethacrylate containing photocrosslinkable chalcone group in the side chain under irradiation of a linearly polarized UV light

    CERN Document Server

    Choi, D H

    2002-01-01

    Photocrosslinkable soluble polyimide and polymethacrylate compound were synthesized for studying the optically induced anisotropy of the thin films. Chalcone group was introduced into the side chain unit of two polymers. We observed a photodimerization behavior between the double bonds in the chalcone group and an optical anisotropy of these materials by irradiation of a linearly polarized UV light (LPL). Optical anisotropy of the thin film was also investigated by using polarized UV absorption spectroscopy.The dynamic property of optical anisotropy in photoreactive polyimide was compared to that in polymethacrylate containing chalcone group in the side chain.

  5. Endocytosis of G protein-coupled receptors is regulated by clathrin light chain phosphorylation.

    Science.gov (United States)

    Ferreira, Filipe; Foley, Matthew; Cooke, Alex; Cunningham, Margaret; Smith, Gemma; Woolley, Robert; Henderson, Graeme; Kelly, Eamonn; Mundell, Stuart; Smythe, Elizabeth

    2012-08-07

    Signaling by transmembrane receptors such as G protein-coupled receptors (GPCRs) occurs at the cell surface and throughout the endocytic pathway, and signaling from the cell surface may differ in magnitude and downstream output from intracellular signaling. As a result, the rate at which signaling molecules traverse the endocytic pathway makes a significant contribution to downstream output. Modulation of the core endocytic machinery facilitates differential uptake of individual cargoes. Clathrin-coated pits are a major entry portal where assembled clathrin forms a lattice around invaginating buds that have captured endocytic cargo. Clathrin assembles into triskelia composed of three clathrin heavy chains and associated clathrin light chains (CLCs). Despite the identification of clathrin-coated pits at the cell surface over 30 years ago, the functions of CLCs in endocytosis have been elusive. In this work, we identify a novel role for CLCs in the regulated endocytosis of specific cargoes. Small interfering RNA-mediated knockdown of either CLCa or CLCb inhibits the uptake of GPCRs. Moreover, we demonstrate that phosphorylation of Ser204 in CLCb is required for efficient endocytosis of a subset of GPCRs and identify G protein-coupled receptor kinase 2 (GRK2) as a kinase that can phosphorylate CLCb on Ser204. Overexpression of CLCb(S204A) specifically inhibits the endocytosis of those GPCRs whose endocytosis is GRK2-dependent. Together, these results indicate that CLCb phosphorylation acts as a discriminator for the endocytosis of specific GPCRs. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Equilibrium and stochastic resonance in finite chains of noisy bistable elements

    International Nuclear Information System (INIS)

    Morillo, Manuel; Gomez-Ordonez, Jose; Casado, Jose Manuel

    2010-01-01

    Graphical abstract: We analyze the dependence of the equilibrium distribution of a collective variable of a chain on relevant parameters including the chain size and its connectivity. We also analyze the stochastic resonance effect of the same variable. - Abstract: Using numerical simulations, we analyze equilibrium properties of finite chains of coupled noisy bistable units and their response to weak time periodic forces. Finite chains with global as well as local (nearest neighbors) coupling are considered. We focus on the study of a collective variable defined as the arithmetic mean of the variables characterizing each element of the chain. By contrast with the case of infinite size chains, where the coexistence of several equilibrium distributions for the same values of parameters is possible, for finite chains just a single equilibrium distribution exists for given values of the parameters. We demonstrate that, regardless of the chain connectivity, there exist transition lines separating regions in parameter space where the equilibrium distribution function is either monomodal or multimodal. The location of the transition line depends on the chain connectivity and the size of the system. For driven chains, the response of the system shows stochastic resonant effects. For the two types of chains considered, both the power spectral amplification and the signal-to-noise ratio of the collective variable are analyzed as the noise strength, the coupling parameter and the number of bistable units in the system are varied. Compared with the effects observed in single unit systems, the collective variable shows a strong enhancement of the stochastic resonance effects.

  7. Phos-tag-based analysis of myosin regulatory light chain phosphorylation in human uterine myocytes.

    Directory of Open Access Journals (Sweden)

    Hector N Aguilar

    Full Text Available The 'phosphate-binding tag' (phos-tag reagent enables separation of phospho-proteins during SDS-PAGE by impeding migration proportional to their phosphorylation stoichiometry. Western blotting can then be used to detect and quantify the bands corresponding to the phospho-states of a target protein. We present a method for quantification of data regarding phospho-states derived from phos-tag SDS-PAGE. The method incorporates corrections for lane-to-lane loading variability and for the effects of drug vehicles thus enabling the comparison of multiple treatments by using the untreated cellular set-point as a reference. This method is exemplified by quantifying the phosphorylation of myosin regulatory light chain (RLC in cultured human uterine myocytes.We have evaluated and validated the concept that, when using an antibody (Ab against the total-protein, the sum of all phosphorylation states in a single lane represents a 'closed system' since all possible phospho-states and phosphoisotypes are detected. Using this approach, we demonstrate that oxytocin (OT and calpeptin (Calp induce RLC kinase (MLCK- and rho-kinase (ROK-dependent enhancements in phosphorylation of RLC at T18 and S19. Treatment of myocytes with a phorbol ester (PMA induced phosphorylation of S1-RLC, which caused a mobility shift in the phos-tag matrices distinct from phosphorylation at S19.We have presented a method for analysis of phospho-state data that facilitates quantitative comparison to a reference control without the use of a traditional 'loading' or 'reference' standard. This analysis is useful for assessing effects of putative agonists and antagonists where all phospho-states are represented in control and experimental samples. We also demonstrated that phosphorylation of RLC at S1 is inducible in intact uterine myocytes, though the signal in the resting samples was not sufficiently abundant to allow quantification by the approach used here.

  8. IG and TR single chain fragment variable (scFv) sequence analysis: a new advanced functionality of IMGT/V-QUEST and IMGT/HighV-QUEST.

    Science.gov (United States)

    Giudicelli, Véronique; Duroux, Patrice; Kossida, Sofia; Lefranc, Marie-Paule

    2017-06-26

    IMGT®, the international ImMunoGeneTics information system® ( http://www.imgt.org ), was created in 1989 in Montpellier, France (CNRS and Montpellier University) to manage the huge and complex diversity of the antigen receptors, and is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. Immunoglobulins (IG) or antibodies and T cell receptors (TR) are managed and described in the IMGT® databases and tools at the level of receptor, chain and domain. The analysis of the IG and TR variable (V) domain rearranged nucleotide sequences is performed by IMGT/V-QUEST (online since 1997, 50 sequences per batch) and, for next generation sequencing (NGS), by IMGT/HighV-QUEST, the high throughput version of IMGT/V-QUEST (portal begun in 2010, 500,000 sequences per batch). In vitro combinatorial libraries of engineered antibody single chain Fragment variable (scFv) which mimic the in vivo natural diversity of the immune adaptive responses are extensively screened for the discovery of novel antigen binding specificities. However the analysis of NGS full length scFv (~850 bp) represents a challenge as they contain two V domains connected by a linker and there is no tool for the analysis of two V domains in a single chain. The functionality "Analyis of single chain Fragment variable (scFv)" has been implemented in IMGT/V-QUEST and, for NGS, in IMGT/HighV-QUEST for the analysis of the two V domains of IG and TR scFv. It proceeds in five steps: search for a first closest V-REGION, full characterization of the first V-(D)-J-REGION, then search for a second V-REGION and full characterization of the second V-(D)-J-REGION, and finally linker delimitation. For each sequence or NGS read, positions of the 5'V-DOMAIN, linker and 3'V-DOMAIN in the scFv are provided in the 'V-orientated' sense. Each V-DOMAIN is fully characterized (gene identification, sequence description, junction analysis, characterization of mutations and amino

  9. Development of a single-chain variable fragment-alkaline phosphatase fusion protein and a sensitive direct competitive chemiluminescent enzyme immunoassay for detection of ractopamine in pork

    Energy Technology Data Exchange (ETDEWEB)

    Dong Jiexian; Li Zhenfeng; Lei Hongtao; Sun Yuanming [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Ducancel, Frederic [CEA, iBiTec-S, Service de Pharmacologie et d' Immnoanalyse (SPI), CEA Saclay, F-91191 Gif sur Yvette (France); Xu Zhenlin [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Boulain, Jean-Claude [CEA, iBiTec-S, Service de Pharmacologie et d' Immnoanalyse (SPI), CEA Saclay, F-91191 Gif sur Yvette (France); Yang Jinyi; Shen Yudong [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China); Wang Hong, E-mail: gzwhongd@63.com [Guangdong Provincial Key Laboratory of Food Quality and Safety, South China Agricultural University, Guangzhou 510642 (China)

    2012-07-29

    Graphical abstract: Detection model of dc-CLEIA based on anti-RAC scFv-AP fusion protein. Highlights: Black-Right-Pointing-Pointer The scFv-AP fusion protein against ractopamine (RAC) was produced. Black-Right-Pointing-Pointer A dc-CLEIA for RAC was developed based on the purified scFv-AP fusion protein. Black-Right-Pointing-Pointer The sensitivity of dc-CLEIA was 10 times as sensitive as dc-ELISA for RAC. Black-Right-Pointing-Pointer Recovery tests from pork samples were studied. Black-Right-Pointing-Pointer Good accuracy was obtained. - Abstract: A rapid, sensitive chemiluminescent enzyme immunoassay (CLEIA) for ractopamine (RAC) based on a single-chain variable fragment (scFv)-alkaline phosphatase (AP) fusion protein was developed. The scFv gene was prepared by cloning the heavy- and light-chain variable region genes (V{sub H} and V{sub L}) from hybridoma cell line AC2, which secretes antibodies against RAC, and assembling V{sub H} and V{sub L} genes with a linker by means of splicing overlap extension polymerase chain reaction. The resulting scFv gene was inserted into the expression vector pLIP6/GN containing AP to produce the fusion protein in Escherichia coli strain BL21. The purified scFv-AP fusion protein was used to develop a direct competitive CLEIA (dcCLEIA) protocol for detection of RAC. The average concentration required for 50% inhibition of binding and the limit of detection of the assay were 0.25 {+-} 0.03 and 0.02 {+-} 0.004 ng mL{sup -1}, respectively, and the linear response range extended from 0.05 to 1.45 ng mL{sup -1}. The assay was 10 times as sensitive as the corresponding enzyme-linked immunosorbent assay based on the same fusion protein. Cross-reactivity studies showed that the fusion protein did not cross react with RAC analogs. DcCLEIA was used to analyze RAC spiked pork samples, and the validation was confirmed by high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS). The results showed a good correlation between

  10. Biased Immunoglobulin Light Chain Gene Usage in the Shark.

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Naik, Ushma; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2015-10-15

    This study of a large family of κ L chain clusters in nurse shark completes the characterization of its classical Ig gene content (two H chain isotypes, μ and ω, and four L chain isotypes, κ, λ, σ, and σ-2). The shark κ clusters are minigenes consisting of a simple VL-JL-CL array, where V to J recombination occurs over an ~500-bp interval, and functional clusters are widely separated by at least 100 kb. Six out of ~39 κ clusters are prerearranged in the germline (germline joined). Unlike the complex gene organization and multistep assembly process of Ig in mammals, each shark Ig rearrangement, somatic or in the germline, appears to be an independent event localized to the minigene. This study examined the expression of functional, nonproductive, and sterile transcripts of the κ clusters compared with the other three L chain isotypes. κ cluster usage was investigated in young sharks, and a skewed pattern of split gene expression was observed, one similar in functional and nonproductive rearrangements. These results show that the individual activation of the spatially distant κ clusters is nonrandom. Although both split and germline-joined κ genes are expressed, the latter are prominent in young animals and wane with age. We speculate that, in the shark, the differential activation of the multiple isotypes can be advantageously used in receptor editing. Copyright © 2015 by The American Association of Immunologists, Inc.

  11. Chemical variability along the value chains of turmeric (Curcuma longa): a comparison of nuclear magnetic resonance spectroscopy and high performance thin layer chromatography.

    Science.gov (United States)

    Booker, Anthony; Frommenwiler, Debora; Johnston, Deborah; Umealajekwu, Chinenye; Reich, Eike; Heinrich, Michael

    2014-03-14

    Herbal medicine value chains have generally been overlooked compared with food commodities. Not surprisingly, revenue generation tends to be weighted towards the end of the chain and consequently the farmers and producers are the lowest paid beneficiaries. Value chains have an impact both on the livelihood of producers and on the composition and quality of products commonly sold locally and globally and consequently on the consumers. In order to understand the impact of value chains on the composition of products, we studied the production conditions for turmeric (Curcuma longa) and the metabolomic composition of products derived from it. We aimed at integrating these two components in order to gain a better understanding of the effect of different value chains on the livelihoods of some producers. This interdisciplinary project uses a mixed methods approach. Case studies were undertaken on two separate sites in India. Data was initially gathered on herbal medicine value chains by means of semi-structured interviews and non-participant observations. Samples were collected from locations in India, Europe and the USA and analysed using (1)H NMR spectroscopy coupled with multivariate analysis software and with high performance thin layer chromatography (HPTLC). We investigate medicinal plant value chains and interpret the impact different value chains have on some aspects of the livelihoods of producers in India and, for the first time, analytically assess the chemical variability and quality implications that different value chains may have on the products available to end users in Europe. There are benefits to farmers that belonged to an integrated chain and the resulting products were subject to a higher standard of processing and storage. By using analytical methods, including HPTLC and (1)H NMR spectroscopy, it has been possible to correlate some variations in product composition for selected producers and identify strengths and weaknesses of some types of value

  12. Bifunctional Rhodamine Probes of Myosin Regulatory Light Chain Orientation in Relaxed Skeletal Muscle Fibers

    Science.gov (United States)

    Brack, Andrew S.; Brandmeier, Birgit D.; Ferguson, Roisean E.; Criddle, Susan; Dale, Robert E.; Irving, Malcolm

    2004-01-01

    The orientation of the regulatory light chain (RLC) region of the myosin heads in relaxed skinned fibers from rabbit psoas muscle was investigated by polarized fluorescence from bifunctional rhodamine (BR) probes cross-linking pairs of cysteine residues introduced into the RLC. Pure 1:1 BR-RLC complexes were exchanged into single muscle fibers in EDTA rigor solution for 30 min at 30°C; ∼60% of the native RLC was removed and stoichiometrically replaced by BR-RLC, and >85% of the BR-RLC was located in the sarcomeric A-bands. The second- and fourth-rank order parameters of the orientation distributions of BR dipoles linking RLC cysteine pairs 100-108, 100-113, 108-113, and 104-115 were calculated from polarized fluorescence intensities, and used to determine the smoothest RLC orientation distribution—the maximum entropy distribution—consistent with the polarized fluorescence data. Maximum entropy distributions in relaxed muscle were relatively broad. At the peak of the distribution, the “lever” axis, linking Cys707 and Lys843 of the myosin heavy chain, was at 70–80° to the fiber axis, and the “hook” helix (Pro830–Lys843) was almost coplanar with the fiber and lever axes. The temperature and ionic strength of the relaxing solution had small but reproducible effects on the orientation of the RLC region. PMID:15041671

  13. Quantifying Short-Chain Chlorinated Paraffin Congener Groups

    NARCIS (Netherlands)

    Yuan, Bo; Bogdal, Christian; Berger, Urs; MacLeod, Matthew; Gebbink, Wouter A.; Alsberg, Tomas; Wit, de Cynthia A.

    2017-01-01

    Accurate quantification of short-chain chlorinated paraffins (SCCPs) poses an exceptional challenge to analytical chemists. SCCPs are complex mixtures of chlorinated alkanes with variable chain length and chlorination level; congeners with a fixed chain length (n) and number of chlorines (m) are

  14. Intraventricular dyssynchrony in light chain amyloidosis: a new mechanism of systolic dysfunction assessed by 3-dimensional echocardiography

    Directory of Open Access Journals (Sweden)

    Truran Seth

    2008-08-01

    Full Text Available Abstract Background Light chain amyloidosis (AL is a rare but often fatal disease due to intractable heart failure. Amyloid deposition leads to diastolic dysfunction and often preserved ejection fraction. We hypothesize that AL is associated with regional systolic dyssynchrony. The aim is to compare left ventricular (LV regional synchrony in AL subjects versus healthy controls using 16-segment dyssynchrony index measured from 3-dimension-al (3D echocardiography. Methods Cardiac 3D echocardiography full volumes were acquired in 10 biopsy-proven AL subjects (60 ± 3 years, 5 females and 10 healthy controls (52 ± 1 years, 5 females. The LV was subdivided into 16 segments and the time from end-diastole to the minimal systolic volume for each of the 16 segments was expressed as a percent of the cycle length. The standard deviations of these times provided a 16-segment dyssynchrony index (16-SD%. 16-SD% was compared between healthy and AL subjects. Results Left ventricular ejection fraction was comparable (control vs. AL: 62.4 ± 0.6 vs. 58.6 ± 2.8%, p = NS. 16-SD% was significantly higher in AL versus healthy subjects (5.93 ± 4.4 vs. 1.67 ± 0.87%, p = 0.003. 16-SD% correlated with left ventricular mass index (R 0.45, p = 0.04 but not to left ventricular ejection fraction. Conclusion Light chain amyloidosis is associated with left ventricular regional systolic dyssynchrony. Regional dyssynchrony may be an unrecognized mechanism of heart failure in AL subjects.

  15. PCR-based clonality analysis of B-cell lymphomas in paraffin-embedded tissues: diagnostic value of immunoglobulin kappa and lambda light chain gene rearrangement investigation.

    Science.gov (United States)

    Amara, Khaled; Trimeche, Mounir; Ziadi, Sonia; Sriha, Badreddine; Mokni, Moncef; Korbi, Sadok

    2006-01-01

    Polymerase chain reaction (PCR)-based analysis, employed for detecting immunoglobulin heavy chain (IgH) gene rearrangements, has become a diagnostic tool widely used in the investigation of B-cell lymphomas, but the overall sensitivity of these methods does not exceed 80%, notably in germinal center (GC) and post-GC B-cell origin lymphomas. Many PCR strategies devised for detecting immunoglobulin light chain (IgL) gene rearrangements have been developed to enhance the clonality detection rates. However, the feasibility of these methods in routine clinical diagnosis using paraffin-embedded tissues has not yet been investigated sufficiently. We studied a large series of 108 cases of B-cell lymphomas, as well as 20 reactive lymphoid tissues using degenerate primers to amplify immunoglobulin kappa (Igkappa) and lambda (Iglambda) light chain genes. B-cell clonality was further investigated using semi-nested PCR for IgH gene rearrangements. B-cell clonality was detected in 74%, 56.5%, and 43.5% of cases using IgH, Igkappa, and Iglambda PCR, respectively. By combining these methods, the clonality detection rate increased to 93.5%. Only polyclonal patterns were noted in reactive lymphoid samples. We concluded that in addition to the established methods for IgH analysis, a PCR-based approach for IgL gene rearrangements analysis improves the clonality detection rate in over 90% of B-cell lymphoma cases using routine histological specimens with poor preservation of the genomic DNA.

  16. Supply Chain Management Practices in Toy Supply Chains

    DEFF Research Database (Denmark)

    Arlbjørn, Jan Stentoft; Johansen, J.; Wong, C. Y.

    2005-01-01

    Purpose - Innovative products usually experience highly unpredictable and variable demand. This is especially valid for the volatile and seasonal toy industry, which produces high obsolete inventory, lost sales and markdown. In such a volatile industry, what supply chain management (SCM) practices...... (traditional mass-production or push-models). These low-responsive practices in the toy supply chain are not caused only by slow knowledge diffusion. SCM know-how is not yet capable of managing such levels of volatility and seasonality. Therefore, explanations of these theoretical gaps and what new theories...... are required for such extreme volatility and seasonality are proposed. Originality/value - It reveals actual SCM practices in a volatile and seasonal supply chain, such that theoretical and practical gaps are identified. Also, it proposes a model to match manufacturing SCM-practices with retailer SCM-practices....

  17. Redeployment-based drug screening identifies the anti-helminthic niclosamide as anti-myeloma therapy that also reduces free light chain production

    International Nuclear Information System (INIS)

    Khanim, F L; Merrick, B A M E; Giles, H V; Jankute, M; Jackson, J B; Giles, L J; Birtwistle, J; Bunce, C M; Drayson, M T

    2011-01-01

    Despite recent therapeutic advancements, multiple myeloma (MM) remains incurable and new therapies are needed, especially for the treatment of elderly and relapsed/refractory patients. We have screened a panel of 100 off-patent licensed oral drugs for anti-myeloma activity and identified niclosamide, an anti-helminthic. Niclosamide, at clinically achievable non-toxic concentrations, killed MM cell lines and primary MM cells as efficiently as or better than standard chemotherapy and existing anti-myeloma drugs individually or in combinations, with little impact on normal donor cells. Cell death was associated with markers of both apoptosis and autophagy. Importantly, niclosamide rapidly reduced free light chain (FLC) production by MM cell lines and primary MM. FLCs are a major cause of renal impairment in MM patients and light chain amyloid and FLC reduction is associated with reversal of tissue damage. Our data indicate that niclosamides anti-MM activity was mediated through the mitochondria with rapid loss of mitochondrial membrane potential, uncoupling of oxidative phosphorylation and production of mitochondrial superoxide. Niclosamide also modulated the nuclear factor-κB and STAT3 pathways in MM cells. In conclusion, our data indicate that MM cells can be selectively targeted using niclosamide while also reducing FLC secretion. Importantly, niclosamide is widely used at these concentrations with minimal toxicity

  18. SINGLE CHAIN VARIABLE FRAGMENTS OF ANTIBODIES AGAINST DIPHTHERIA TOXIN B-SUBUNIT ISOLATED FROM PHAGE DISPLAY HUMAN ANTIBODY LIBRARY

    Directory of Open Access Journals (Sweden)

    Oliinyk O. S.

    2014-02-01

    Full Text Available Diphtheria toxin is an exoantigen of Corynebacterium diphtheriae that inhibits protein synthesis and kills sensitive cells. The aim of this study was to obtain human recombinant single-chain variable fragment (scFv antibodies against receptor-binding B subunit of diphtheria toxin. 12 specific clones were selected after three rounds of a phage display naїve (unimmunized human antibody library against recombinant B-subunit. scFv DNA inserts from these 12 clones were digested with MvaI, and 6 unique restriction patterns were found. Single-chain antibodies were expressed in Escherichia coli XL1-blue. The recombinant proteins were characterized by immunoblotting of bacterial extracts and detection with an anti-E-tag antibody. The toxin B-subunit-binding function of the single-chain antibody was shown by ELISA. The affinity constants for different clones were found to be from 106 to 108 М–1. Due to the fact, that these antibody fragments recognized epitopes in the receptor-binding Bsubunit of diphtheria toxin, further studies are interesting to evaluate their toxin neutralization properties and potential for therapeutic applications. Obtained scFv-antibodies can also be used for detection and investigation of biological properties of diphtheria toxin.

  19. Glycogen synthase kinase 3 phosphorylates kinesin light chains and negatively regulates kinesin-based motility

    Science.gov (United States)

    Morfini, Gerardo; Szebenyi, Gyorgyi; Elluru, Ravindhra; Ratner, Nancy; Brady, Scott T.

    2002-01-01

    Membrane-bounded organelles (MBOs) are delivered to different domains in neurons by fast axonal transport. The importance of kinesin for fast antero grade transport is well established, but mechanisms for regulating kinesin-based motility are largely unknown. In this report, we provide biochemical and in vivo evidence that kinesin light chains (KLCs) interact with and are in vivo substrates for glycogen synthase kinase 3 (GSK3). Active GSK3 inhibited anterograde, but not retrograde, transport in squid axoplasm and reduced the amount of kinesin bound to MBOs. Kinesin microtubule binding and microtubule-stimulated ATPase activities were unaffected by GSK3 phosphorylation of KLCs. Active GSK3 was also localized preferentially to regions known to be sites of membrane delivery. These data suggest that GSK3 can regulate fast anterograde axonal transport and targeting of cargos to specific subcellular domains in neurons.

  20. Crystal Structures of the Tetratricopeptide Repeat Domains of Kinesin Light Chains: Insight into Cargo Recognition Mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, Haizhong; Lee, Han Youl; Tong, Yufeng; Hong, Bum-Soo; Kim, Kyung-Phil; Shen, Yang; Lim, Kyung Jik; Mackenzie, Farrell; Tempel, Wolfram; Park, Hee-Won (SGC-Toronto); (PPCS); (Toronto)

    2012-10-23

    Kinesin-1 transports various cargos along the axon by interacting with the cargos through its light chain subunit. Kinesin light chains (KLC) utilize its tetratricopeptide repeat (TPR) domain to interact with over 10 different cargos. Despite a high sequence identity between their TPR domains (87%), KLC1 and KLC2 isoforms exhibit differential binding properties towards some cargos. We determined the structures of human KLC1 and KLC2 tetratricopeptide repeat (TPR) domains using X-ray crystallography and investigated the different mechanisms by which KLCs interact with their cargos. Using isothermal titration calorimetry, we attributed the specific interaction between KLC1 and JNK-interacting protein 1 (JIP1) cargo to residue N343 in the fourth TRP repeat. Structurally, the N343 residue is adjacent to other asparagines and lysines, creating a positively charged polar patch within the groove of the TPR domain. Whereas, KLC2 with the corresponding residue S328 did not interact with JIP1. Based on these finding, we propose that N343 of KLC1 can form 'a carboxylate clamp' with its neighboring asparagine to interact with JIP1, similar to that of HSP70/HSP90 organizing protein-1's (HOP1) interaction with heat shock proteins. For the binding of cargos shared by KLC1 and KLC2, we propose a different site located within the groove but not involving N343. We further propose a third binding site on KLC1 which involves a stretch of polar residues along the inter-TPR loops that may form a network of hydrogen bonds to JIP3 and JIP4. Together, these results provide structural insights into possible mechanisms of interaction between KLC TPR domains and various cargo proteins.

  1. Grasping the nettle: A bacterial invasin that targets immunoglobulin variable domains.

    Science.gov (United States)

    Barlow, Paul

    2018-06-01

    In a new paper, the protein InvD from Yersinia pseudotuberculosis , a zoonotic pathogen, is shown to assist late-stage invasion of intestinal epithelia. Remarkably, InvD acts by binding the Fab region of IgG or IgA. It straddles adjacent light-chain and heavy-chain variable domains, but its binding is different from that of antigens in that complementarity-determining regions do not participate. Structure determination revealed that its Fab-interacting domain adopts an immunoglobulin-like fold, fused to the preceding immunoglobulin-like domain and carried on a long stalk anchored to the bacterial outer membrane. Possible roles of this unusual host-pathogen interaction include avoidance of clearance from the intestine by secretory IgA. © 2018 Barlow.

  2. Botulinum neurotoxin type A radiolabeled at either the light or the heavy chain

    International Nuclear Information System (INIS)

    Dekleva, M.L.; DasGupta, B.R.; Sathyamoorthy, V.

    1989-01-01

    Botulinum neurotoxin (NT) has two distinct structural regions called L and H chains (approximately 50 and approximately 100 kDa, respectively). Although the H chain is responsible for binding of the NT to neuronal cells, it is not known which of the subunits is internalized and therefore responsible for causing the blockage of acetylcholine release in susceptible neuronal cells. In this report we describe for the first time the preparation of type A NT which is selectively radiolabeled at either the L or the H chain subunit. Such NT preparations will be useful as tools for determining the distribution of L and H chains in poisoned neuronal cells and the role that each subunit plays in inducing toxicity. The L and H chains of the NT (approximately 150 kDa) were separated, purified, and then individually radiolabeled by reductive methylation of the lysine residues using [3H]- or [14C]formaldehyde. The labeled L and H chains were reconjugated with the complementary unlabeled L and H chains. Formation of -S-S- and noncovalent bonds between the L and H chains regenerated the approximately 150 kDa NT. Autoradiographs of sodium dodecyl sulfate polyacrylamide gels confirmed that each reconstituted NT preparation was labeled at only one subunit chain. NT selectively labeled at either the L or the H chain had specific radioactivities of ca. 25-30 and 45-55 microCi/mumol, respectively, and toxicity (mouse LD50/mg protein) values of 2.2 +/- 1.1 X 10(7) and 3.0 +/- 1.0 X 10(7), respectively. A linear increase in the specific radioactivity of L and H chain subunits was observed with increasing concentrations of 3H- or 14C-labeled formaldehyde in the reaction mixture and with increasing concentrations of L or H chain in the reaction mixture

  3. A high affinity monoclonal antibody recognizing the light chain of human coagulating factor VII.

    Science.gov (United States)

    Sarial, Sheila; Asadi, Farzad; Jeddi-Tehrani, Mahmood; Hadavi, Reza; Bayat, Ali Ahmad; Mahmoudian, Jafar; Taghizadeh-Jahed, Masoud; Shokri, Fazel; Rabbani, Hodjattallah

    2012-12-01

    Factor VII (FVII) is a serine protease-coagulating element responsible for the initiation of an extrinsic pathway of clot formation. Here we generated and characterized a high affinity monoclonal antibody that specifically recognizes human FVII. Recombinant human FVII (rh-FVII) was used for the production of a monoclonal antibody using BALB/c mice. The specificity of the antibody was determined by Western blot using plasma samples from human, mouse, sheep, goat, bovine, rabbit, and rat. Furthermore, the antibody was used to detect transiently expressed rh-FVII in BHK21 cell line using Western blot and sandwich ELISA. A mouse IgG1 (kappa chain) monoclonal antibody clone 1F1-B11 was produced against rh-FVII. The affinity constant (K(aff)) of the antibody was calculated to be 6.4×10(10) M(-1). The antibody could specifically recognize an epitope on the light chain of hFVII, with no reactivity with factor VII from several other animals. In addition, transiently expressed rh-FVII in BHK21 cells was recognized by 1F1-B11. The high affinity as well as the specificity of 1F1-B11 for hFVII will facilitate the affinity purification of hFVII and also production of FVII deficient plasma and minimizes the risk of bovine FVII contamination when fetal bovine serum-supplemented media are used for production and subsequent purification of rh-FVII.

  4. Effects of Variable Production Rate and Time-Dependent Holding Cost for Complementary Products in Supply Chain Model

    Directory of Open Access Journals (Sweden)

    Mitali Sarkar

    2017-01-01

    Full Text Available Recently, a major trend is going to redesign a production system by controlling or making variable the production rate within some fixed interval to maintain the optimal level. This strategy is more effective when the holding cost is time-dependent as it is interrelated with holding duration of products and rate of production. An effort is made to make a supply chain model (SCM to show the joint effect of variable production rate and time-varying holding cost for specific type of complementary products, where those products are made by two different manufacturers and a common retailer makes them bundle and sells bundles to end customers. Demand of each product is specified by stochastic reservation prices with a known potential market size. Those players of the SCM are considered with unequal power. Stackelberg game approach is employed to obtain global optimum solution of the model. An illustrative numerical example, graphical representation, and managerial insights are given to illustrate the model. Results prove that variable production rate and time-dependent holding cost save more than existing literature.

  5. Light interception efficiency explained by two simple variables: a test using a diversity of small- to medium-sized woody plants

    NARCIS (Netherlands)

    Duursma, R.A.; Falster, D.S.; Valladares, F.; Sterck, F.J.; Pearcy, R.W.; Lusk, C.; Sendall, K.M.; Nordenstahl, M.; Houter, N.C.; Atwell, B.J.; Kelly, N.; Kelly, J.W.G.; Liberloo, M.; Tissue, D.T.; Medlyn, B.E.; Ellsworth, D.S.

    2012-01-01

    Plant light interception efficiency is a crucial determinant of carbon uptake by individual plants and by vegetation. Our aim was to identify whole-plant variables that summarize complex crown architecture, which can be used to predict light interception efficiency. •We gathered the largest database

  6. Excessive amounts of mu heavy chain block B-cell development.

    Science.gov (United States)

    Zhu, Lingqiao; Chang, Cheong-Hee; Dunnick, Wesley

    2011-09-01

    Antigen-independent B-cell development occurs in several stages that depend on the expression of Ig heavy and light chain. We identified a line of mice that lacked mature B cells in the spleen. This mouse line carried approximately 11 copies of a transgene of the murine heavy chain constant region locus, and B-lineage cells expressed excessive amounts of the intracellular μ heavy chain. B-cell development failed in the bone marrow at the pro/pre B-cell transition, and examination of other lines with various copy numbers of the same transgene suggested that deficiencies in B-cell development increased with increased transgene copy number. Expression of a transgenic (Tg) light chain along with the Tg μ heavy chain led to minimal rescue of B-cell development in the bone marrow and B cells in the spleen. There are several potential mechanisms for the death of pro/pre B cells as a consequence of excess heavy chain expression.

  7. A global, myosin light chain kinase-dependent increase in myosin II contractility accompanies the metaphase-anaphase transition in sea urchin eggs.

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R; Shuster, Charles B

    2006-09-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase-anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase-anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus.

  8. A Global, Myosin Light Chain Kinase-dependent Increase in Myosin II Contractility Accompanies the Metaphase–Anaphase Transition in Sea Urchin Eggs

    Science.gov (United States)

    Lucero, Amy; Stack, Christianna; Bresnick, Anne R.

    2006-01-01

    Myosin II is the force-generating motor for cytokinesis, and although it is accepted that myosin contractility is greatest at the cell equator, the temporal and spatial cues that direct equatorial contractility are not known. Dividing sea urchin eggs were placed under compression to study myosin II-based contractile dynamics, and cells manipulated in this manner underwent an abrupt, global increase in cortical contractility concomitant with the metaphase–anaphase transition, followed by a brief relaxation and the onset of furrowing. Prefurrow cortical contractility both preceded and was independent of astral microtubule elongation, suggesting that the initial activation of myosin II preceded cleavage plane specification. The initial rise in contractility required myosin light chain kinase but not Rho-kinase, but both signaling pathways were required for successful cytokinesis. Last, mobilization of intracellular calcium during metaphase induced a contractile response, suggesting that calcium transients may be partially responsible for the timing of this initial contractile event. Together, these findings suggest that myosin II-based contractility is initiated at the metaphase–anaphase transition by Ca2+-dependent myosin light chain kinase (MLCK) activity and is maintained through cytokinesis by both MLCK- and Rho-dependent signaling. Moreover, the signals that initiate myosin II contractility respond to specific cell cycle transitions independently of the microtubule-dependent cleavage stimulus. PMID:16837551

  9. Production of bifunctional proteins by Aspergillus awamori: Llama variable heavy chain antibody fragment (VHH) R9 coupled to Arthromyces ramosus peroxidase (ARP)

    NARCIS (Netherlands)

    Joosten, V.; Roelofs, M.S.; Dries, N. van den; Goosen, T.; Verrips, C.T.; Hondel, C.A.M.J.J. van den; Lokman, B.C.

    2005-01-01

    The Arthromyces ramosus peroxidase gene (arp) was genetically fused to either the 5′- or 3′-terminal ends of the gene encoding llama variable heavy chain antibody fragment VHH R9, resulting in the fusion expression cassettes ARP-R9 or R9-ARP. Aspergillus awamori transformants were obtained which

  10. The effect of work pace on workload, motor variability and fatigue during simulated light assembly work

    NARCIS (Netherlands)

    Bosch, T.; Mathiassen, S.E.; Visser, B.; Looze, M.D. de; Dieën, J.V. van

    2011-01-01

    This study investigated the effect of work pace on workload, motor variability and fatigue during light assembly work. Upper extremity kinematics and electromyography (EMG) were obtained on a cycle-to-cycle basis for eight participants during two conditions, corresponding to "normal" and "high" work

  11. Definition of organ involvement and treatment response in immunoglobulin light chain amyloidosis (AL) : A consensus opinion from the 10th International Symposium on Amyloid and Amyloidosis

    NARCIS (Netherlands)

    Gertz, MA; Comenzo, R; Falk, RH; Fermand, JP; Hazenberg, BP; Hawkins, PN; Merlini, G; Moreau, P; Ronco, P; Sanchorawala, [No Value; Sezer, O; Solomon, A; Grateau, G

    We undertook this study to develop uniformly accepted criteria for the definition of organ involvement and response for patients on treatment protocols for immunoglobulin light-chain amyloidosis (AL). A consensus panel was convened comprising 13 specialists actively involved in the treatment of

  12. Boosting nearest-neighbour to long-range integrable spin chains

    International Nuclear Information System (INIS)

    Bargheer, Till; Beisert, Niklas; Loebbert, Florian

    2008-01-01

    We present an integrability-preserving recursion relation for the explicit construction of long-range spin chain Hamiltonians. These chains are generalizations of the Haldane–Shastry and Inozemtsev models and they play an important role in recent advances in string/gauge duality. The method is based on arbitrary nearest-neighbour integrable spin chains and it sheds light on the moduli space of deformation parameters. We also derive the closed chain asymptotic Bethe equations. (letter)

  13. Drivers of close supply chain collaboration: one size fits all?

    NARCIS (Netherlands)

    de Leeuw, S.L.J.M.; Fransoo, J.C.

    2009-01-01

    Purpose - The purpose of this paper is to investigate the antecedents of close supply chain collaboration and to develop a multi-variable conceptual model of factors that drive the need for close supply chain collaboration. Design/methodology/approach - A multi-variable conceptual model is developed

  14. Antibody Heavy Chain Variable Domains of Different Germline Gene Origins Diversify through Different Paths

    Directory of Open Access Journals (Sweden)

    Ufuk Kirik

    2017-11-01

    Full Text Available B cells produce antibodies, key effector molecules in health and disease. They mature their properties, including their affinity for antigen, through hypermutation events; processes that involve, e.g., base substitution, codon insertion and deletion, often in association with an isotype switch. Investigations of antibody evolution define modes whereby particular antibody responses are able to form, and such studies provide insight important for instance for development of efficient vaccines. Antibody evolution is also used in vitro for the design of antibodies with improved properties. To better understand the basic concepts of antibody evolution, we analyzed the mutational paths, both in terms of amino acid substitution and insertions and deletions, taken by antibodies of the IgG isotype. The analysis focused on the evolution of the heavy chain variable domain of sets of antibodies, each with an origin in 1 of 11 different germline genes representing six human heavy chain germline gene subgroups. Investigated genes were isolated from cells of human bone marrow, a major site of antibody production, and characterized by next-generation sequencing and an in-house bioinformatics pipeline. Apart from substitutions within the complementarity determining regions, multiple framework residues including those in protein cores were targets of extensive diversification. Diversity, both in terms of substitutions, and insertions and deletions, in antibodies is focused to different positions in the sequence in a germline gene-unique manner. Altogether, our findings create a framework for understanding patterns of evolution of antibodies from defined germline genes.

  15. Analysis of optically variable devices using a photometric light-field approach

    Science.gov (United States)

    Soukup, Daniel; Å tolc, Svorad; Huber-Mörk, Reinhold

    2015-03-01

    Diffractive Optically Variable Image Devices (DOVIDs), sometimes loosely referred to as holograms, are popular security features for protecting banknotes, ID cards, or other security documents. Inspection, authentication, as well as forensic analysis of these security features are still demanding tasks requiring special hardware tools and expert knowledge. Existing equipment for such analyses is based either on a microscopic analysis of the grating structure or a point-wise projection and recording of the diffraction patterns. We investigated approaches for an examination of DOVID security features based on sampling the Bidirectional Reflectance Distribution Function (BRDF) of DOVIDs using photometric stereo- and light-field-based methods. Our approach is demonstrated on the practical task of automated discrimination between genuine and counterfeited DOVIDs on banknotes. For this purpose, we propose a tailored feature descriptor which is robust against several expected sources of inaccuracy but still specific enough for the given task. The suggested approach is analyzed from both theoretical as well as practical viewpoints and w.r.t. analysis based on photometric stereo and light fields. We show that especially the photometric method provides a reliable and robust tool for revealing DOVID behavior and authenticity.

  16. Drivers of close supply chain collaboration : one size fits all?

    NARCIS (Netherlands)

    Leeuw, de S.L.J.M.; Fransoo, J.C.

    2009-01-01

    Purpose – The purpose of this paper is to investigate the antecedents of close supply chain collaboration and to develop a multi-variable conceptual model of factors that drive the need for close supply chain collaboration. Design/methodology/approach – A multi-variable conceptual model is developed

  17. Supply chain dynamics in healthcare services.

    Science.gov (United States)

    Samuel, Cherian; Gonapa, Kasiviswanadh; Chaudhary, P K; Mishra, Ananya

    2010-01-01

    The purpose of this paper is to analyse health service supply chain systems. A great deal of literature is available on supply chain management in finished goods inventory situations; however, little research exists on managing service capacity when finished goods inventories are absent. System dynamics models for a typical service-oriented supply chain such as healthcare processes are developed, wherein three service stages are presented sequentially. Just like supply chains with finished goods inventory, healthcare service supply chains also show dynamic behaviour. Comparing options, service reduction, and capacity adjustment delays showed that reducing capacity adjustment and service delays gives better results. The study is confined to health service-oriented supply chains. Further work includes extending the study to service-oriented supply chains with parallel processing, i.e. having more than one stage to perform a similar operation and also to study the behaviour in service-oriented supply chains that have re-entrant orders and applications. Specific case studies can also be developed to reveal factors relevant to particular service-oriented supply chains. The paper explains the bullwhip effect in healthcare service-oriented supply chains. Reducing stages and capacity adjustment are strategic options for service-oriented supply chains. The paper throws light on policy options for managing healthcare service-oriented supply chain dynamics.

  18. Variability in dose estimates associated with the food-chain transport and ingestion of selected radionuclides

    International Nuclear Information System (INIS)

    Hoffman, F.O.; Gardner, R.H.; Eckerman, K.F.

    1982-06-01

    Dose predictions for the ingestion of 90 Sr and 137 Cs, using aquatic and terrestrial food chain transport models similar to those in the Nuclear Regulatory Commission's Regulatory Guide 1.109, are evaluated through estimating the variability of model parameters and determining the effect of this variability on model output. The variability in the predicted dose equivalent is determined using analytical and numerical procedures. In addition, a detailed discussion is included on 90 Sr dosimetry. The overall estimates of uncertainty are most relevant to conditions where site-specific data is unavailable and when model structure and parameter estimates are unbiased. Based on the comparisons performed in this report, it is concluded that the use of the generic default parameters in Regulatory Guide 1.109 will usually produce conservative dose estimates that exceed the 90th percentile of the predicted distribution of dose equivalents. An exception is the meat pathway for 137 Cs, in which use of generic default values results in a dose estimate at the 24th percentile. Among the terrestrial pathways of exposure, the non-leafy vegetable pathway is the most important for 90 Sr. For 90 Sr, the parameters for soil retention, soil-to-plant transfer, and internal dosimetry contribute most significantly to the variability in the predicted dose for the combined exposure to all terrestrial pathways. For 137 Cs, the meat transfer coefficient the mass interception factor for pasture forage, and the ingestion dose factor are the most important parameters. The freshwater finfish bioaccumulation factor is the most important parameter for the dose prediction of 90 Sr and 137 Cs transported over the water-fish-man pathway

  19. Emission lines in the hydrogen-deficient variable MV Sagittarii near maximum light

    International Nuclear Information System (INIS)

    Herbig, G.H.

    1975-01-01

    The H-deficient R CrB type variable MV Sgr near maximum light shows a rich emission spectrum in the 5800--8600 A region. Most of these lines are due to Fe ii, but Si ii, N i, O i, and Hα also are present. Such a spectrum has not been observed in any other R CrB star, but there is some resemblance to v Sgr. The emission lines in MV Sgr probably originate in an extended region of low temperature, which may also be responsible for the infrared excess observed by Feast and Glass

  20. CSF free light chain identification of demyelinating disease: comparison with oligoclonal banding and other CSF indexes.

    Science.gov (United States)

    Gurtner, Kari M; Shosha, Eslam; Bryant, Sandra C; Andreguetto, Bruna D; Murray, David L; Pittock, Sean J; Willrich, Maria Alice V

    2018-02-19

    Cerebrospinal fluid (CSF) used in immunoglobulin gamma (IgG) index testing and oligoclonal bands (OCBs) are common laboratory tests used in the diagnosis of multiple sclerosis. The measurement of CSF free light chains (FLC) could pose as an alternative to the labor-intensive isoelectric-focusing (IEF) gels used for OCBs. A total of 325 residual paired CSF and serum specimens were obtained after physician-ordered OCB IEF testing. CSF kappa (cKFLC) and lambda FLC (cLFLC), albumin and total IgG were measured. Calculations were performed based on combinations of analytes: CSF sum of kappa and lambda ([cKFLC+cLFLC]), kappa-index (K-index) ([cKFLC/sKFLC]/[CSF albumin/serum albumin]), kappa intrathecal fraction (KFLCIF) {([cKFLC/sKFLC]-[0.9358×CSF albumin/serum albumin]^[0.6687×sKFLC]/cKFLC)} and IgG-index ([CSF IgG/CSF albumin]/[serum IgG/serum albumin]). Patients were categorized as: demyelination (n=67), autoimmunity (n=53), non-inflammatory (n=50), inflammation (n=38), degeneration (n=28), peripheral neuropathy (n=24), infection (n=13), cancer (n=11), neuromyelitis optica (n=10) and others (n=31). cKFLC measurement used alone at a cutoff of 0.0611 mg/dL showed >90% agreement to OCBs, similar or better performance than all other calculations, reducing the number of analytes and variables. When cases of demyelinating disease were reviewed, cKFLC measurements showed 86% clinical sensitivity/77% specificity. cKFLC alone demonstrates comparable performance to OCBs along with increased sensitivity for demyelinating diseases. Replacing OCB with cKFLC would alleviate the need for serum and CSF IgG and albumin and calculated conversions. cKFLC can overcome challenges associated with performance, interpretation, and cost of traditional OCBs, reducing costs and maintaining sensitivity and specificity supporting MS diagnosis.

  1. ASSESSMENT OF THE RESIDUAL TUMOR IN PATIENTS WITH MULTIPLE MYELOMA BASED ON THE ANALYSIS OF THE FREE LIGHT CHAINS OF IMMUNOGLOBULINS IN BLOOD SERUM

    Directory of Open Access Journals (Sweden)

    T. A. Мitina

    2013-01-01

    Full Text Available Efficiency of the multiple myeloma treatment with chemotherapy including bortezomib was assessed based on determination of the level of immunoglobulin free light chains in blood serum. The method enables estimation of changes in kinetic parameters of the residual tumor, detection of the disease course prognosis, and the choice of the optimal approach to the disease therapy.

  2. Super-light concrete with pearl-chains

    DEFF Research Database (Denmark)

    Hertz, Kristian Dahl

    2009-01-01

    with large spans for bridges, factories, warehouses, shopping centres, car parks, assembly and sports halls and so on. The new structures are new applications for well-understood components, so it is not necessary to prove that they are possible. However, the paper presents tests that were made to illustrate...... half that of similar structures in concrete and steel. They are heat-insulating, fire-resistant and they open up the possibility for large spans and the creation of advanced shapes. Fields of application include roofs, shells, beams, columns, walls, façades, offshore structures, tunnels and structures...... the applicability and to reveal any potential hidden problems. Continuing research will aim to reduce the weight and thereby the resource consumption further. In addition, the paper introduces pearl-chain reinforcement, which is a new principle for creating compression and tension zones. A small number of simple...

  3. Managing Distance Education Institutions through Value Chain Analysis: the Nigerian Experience.

    Science.gov (United States)

    Aderinto, J. A.; Akintayo, M. O.

    Value chain analysis can gauge, analyze, and predict organization effects to control cost in light of achieving strategic organization objectives of distance education. Value chain analysis enables organizations to accomplish their goal or mission through cost effectiveness or differentiation. The value chain activity structure in a distance…

  4. Mechanisms of interaction of monochromatic visible light with cells

    Science.gov (United States)

    Karu, Tiina I.

    1996-01-01

    Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a3 in mitochondria). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O'2- production, and photodynamic action and 1O2 production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These reactions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low- power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Besides explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation for some clinical effects of irradiation, for example the positive

  5. Production of bifunctional proteins by Aspergillus awamori: Llama variable heavy chain antibody fragment (V-HH) R9 coupled to Arthromyces ramosus peroxidase (ARP)

    NARCIS (Netherlands)

    Joosten, V.; Roelofs, M.S.; Dries, van den N.; Goosen, T.; Verrips, C.T.; Hondel, van den C.A.M.J.J.; Lokman, B.C.

    2005-01-01

    The Arthromyces ramosus peroxidase gene (arp) was genetically fused to either the 5'- or 3'-terminal ends of the gene encoding llama variable heavy chain antibody fragment V-HH R9, resulting in the fusion expression cassettes ARP-R9 or R9-ARP. Aspergillus awamori transformants were obtained which

  6. Variable-temperature Microwave Impedance Microscope with Light Stimulation for Research on Photo-induced Phase Transitions

    Science.gov (United States)

    2017-07-24

    SECURITY CLASSIFICATION OF: The DURIP program "Variable-temperature Microwave Impedance Microscope with Light Stimulation for Research on Photo... Stimulation for Research on Photo- induced Phase Transitions The views, opinions and/or findings contained in this report are those of the author(s) and should...reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions

  7. Myosin Light Chain Kinase Mediates Intestinal Barrier Disruption following Burn Injury

    Science.gov (United States)

    Chen, Chuanli; Wang, Pei; Su, Qin; Wang, Shiliang; Wang, Fengjun

    2012-01-01

    Background Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC) phosphorylation mediated by MLC kinase (MLCK) is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. Methodology/Principal Findings Male balb/c mice were assigned randomly to either sham burn (control) or 30% total body surface area (TBSA) full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg), an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC)-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. Conclusions/Significance The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury. PMID:22529961

  8. Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome.

    Science.gov (United States)

    Wang, Chen; Su, Wei; Cai, Qian-Qian; Cai, Hao; Ji, Wei; Di, Qian; Duan, Ming-Hui; Cao, Xin-Xin; Zhou, Dao-Bin; Li, Jian

    2016-07-01

    POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype-specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty-six patients (73%; 95% confidence interval, 63-82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression-free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34-35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post-therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression-free survival (P = 0.019; HR 4.30, 95% CI 1.27-14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Demand management in Multi-Stage Distribution Chain

    NARCIS (Netherlands)

    de Kok, T.; Janssen, F.B.S.L.P.

    1996-01-01

    In this paper we discuss demand management problems in a multi-stage distribution chain.We focus on distribution chains where demand processes have high variability due to a few large customer orders.We give a possible explanation, and suggest two simple procedures that help to smooth demand.It is

  10. Tropical food chains: Governance regimes for quality management

    NARCIS (Netherlands)

    Ruben, R.; Boekel, van M.A.J.S.; Tilburg, van A.; Trienekens, J.H.

    2007-01-01

    International supply chains of vulnerable tropical food products face major problems in the fields of quality performance and coordination between supply chain partners. Degradation and variability of quality, segmentation of supply networks and scattered production by smallholder producers could

  11. Dependence of the product chain-length on detergents for long-chain E-polyprenyl diphosphate synthases

    Science.gov (United States)

    Pan, Jian-Jung; Ramamoorthy, Gurusankar; Poulter, C. Dale

    2013-01-01

    Long-chain E-polyprenyl diphosphate synthases (E-PDS) catalyze repetitive addition of isopentenyl diphosphate (IPP) to the growing prenyl chain of an allylic diphosphate. The polyprenyl diphosphate products are required for the biosynthesis of ubiquinones and menaquinones required for electron transport during oxidative phosphorylation to generate ATP. In vitro, the long-chain PDSs require addition of phospholipids or detergents to the assay buffer to enhance product release and maintain efficient turnover. During preliminary assays of product chain-length with anionic, zwitterionic, and non-ionic detergents, we discovered considerable variability. Examination of a series of non-ionic PEG detergents with several long-chain E-PDSs from different organisms revealed that in vitro incubations with nonaethylene glycol monododecyl ether or Triton X-100 typically gave chain lengths that corresponded to those of the isoprenoid moieties in respiratory quinones synthesized in vivo. In contrast incubations in buffer with n-butanol, CHAPS, DMSO, n-octyl-β-glucopyranoside, or β-cyclodextrin or in buffer without detergent typically proceeded more slowly and gave a broad range of chain lengths. PMID:23802587

  12. Smart management of sample dilution using an artificial neural network to achieve streamlined processes and saving resources: the automated nephelometric testing of serum free light chain as case study.

    Science.gov (United States)

    Ialongo, Cristiano; Pieri, Massimo; Bernardini, Sergio

    2017-02-01

    Saving resources is a paramount issue for the modern laboratory, and new trainable as well as smart technologies can be used to allow the automated instrumentation to manage samples more efficiently in order to achieve streamlined processes. In this regard the serum free light chain (sFLC) testing represents an interesting challenge, as it usually causes using a number of assays before achieving an acceptable result within the analytical range. An artificial neural network based on the multi-layer perceptron (MLP-ANN) was used to infer the starting dilution status of sFLC samples based on the information available through the laboratory information system (LIS). After the learning phase, the MLP-ANN simulation was applied to the nephelometric testing routinely performed in our laboratory on a BN ProSpec® System analyzer (Siemens Helathcare) using the N Latex FLC kit. The MLP-ANN reduced the serum kappa free light chain (κ-FLC) and serum lambda free light chain (λ-FLC) wasted tests by 69.4% and 70.8% with respect to the naïve stepwise dilution scheme used by the automated analyzer, and by 64.9% and 66.9% compared to a "rational" dilution scheme based on a 4-step dilution. Although it was restricted to follow-up samples, the MLP-ANN showed good predictive performance, which alongside the possibility to implement it in any automated system, made it a suitable solution for achieving streamlined laboratory processes and saving resources.

  13. May the variable magnetic field and pulse red light induce synergy effects in respiratory burst of neutrophils in vitro?

    International Nuclear Information System (INIS)

    Nawrocka - Bogusz, H; Jaroszyk, F

    2011-01-01

    We investigated the effect of the red light (R) (630 nm), magnetic field (MF) and magnetic field combined with the red light (MF+R) upon reactive oxygen species (ROS) production by neutrophils in vitro. The object of the research was hydrogen peroxide (H 2 O 2 ) formation during neutrophils respiratory burst or within steady-state. Blood from healthy volunteers was used for the purpose of the study. Flow cytometry method, using transformation of DCFH-DA (2'7'-dichlorofluorescin diacetate) to the fluorescent DCF (2'7'-dichlorofluorescin), was used for estimation of hydrogen peroxide production. The variable magnetic field of ELF range of the mean induction equals 26.7(μT), the red light at the energy density of 1.17(J/cm 2 ) and their combination were applied for 30 minutes each. The fundamental frequency of pulses was 180÷ 195 Hz. A statistically significant decrease of H 2 O 2 production by neutrophils was observed. The level of the decrease was in the range of 10-30% and was dependent on the kind of applied physical factors and whether neutrophils were stimulated or not. The observation showed that the variable magnetic field combined with red light do not induce the synergy effect.

  14. Increased Prognostic Value of Query Amyloid Late Enhancement Score in Light-Chain Cardiac Amyloidosis.

    Science.gov (United States)

    Wan, Ke; Sun, Jiayu; Han, Yuchi; Liu, Hong; Yang, Dan; Li, Weihao; Wang, Jie; Cheng, Wei; Zhang, Qing; Zeng, Zhi; Chen, Yucheng

    2018-02-23

    Late gadolinium enhancement (LGE) pattern is a powerful imaging biomarker for prognosis of cardiac amyloidosis. It is unknown if the query amyloid late enhancement (QALE) score in light-chain (AL) amyloidosis could provide increased prognostic value compared with LGE pattern.Methods and Results:Seventy-eight consecutive patients with AL amyloidosis underwent contrast-enhanced cardiovascular magnetic resonance imaging. Patients with cardiac involvement were grouped by LGE pattern and analyzed using QALE score. Receiver operating characteristic curve was used to identify the optimal cut-off for QALE score in predicting all-cause mortality. Survival of these patients was analyzed with the Kaplan-Meier method and multivariate Cox regression. During a median follow-up of 34 months, 53 of 78 patients died. The optimal cut-off for QALE score to predict mortality at 12-month follow-up was 9.0. On multivariate Cox analysis, QALE score ≥9 (HR, 5.997; 95% CI: 2.665-13.497; Pvalue in AL cardiac amyloidosis. QALE score ≥9 has added value to differentiate prognosis in AL amyloidosis patients with a subendocardial LGE pattern.

  15. An Auxiliary Variable Method for Markov Chain Monte Carlo Algorithms in High Dimension

    Directory of Open Access Journals (Sweden)

    Yosra Marnissi

    2018-02-01

    Full Text Available In this paper, we are interested in Bayesian inverse problems where either the data fidelity term or the prior distribution is Gaussian or driven from a hierarchical Gaussian model. Generally, Markov chain Monte Carlo (MCMC algorithms allow us to generate sets of samples that are employed to infer some relevant parameters of the underlying distributions. However, when the parameter space is high-dimensional, the performance of stochastic sampling algorithms is very sensitive to existing dependencies between parameters. In particular, this problem arises when one aims to sample from a high-dimensional Gaussian distribution whose covariance matrix does not present a simple structure. Another challenge is the design of Metropolis–Hastings proposals that make use of information about the local geometry of the target density in order to speed up the convergence and improve mixing properties in the parameter space, while not being too computationally expensive. These two contexts are mainly related to the presence of two heterogeneous sources of dependencies stemming either from the prior or the likelihood in the sense that the related covariance matrices cannot be diagonalized in the same basis. In this work, we address these two issues. Our contribution consists of adding auxiliary variables to the model in order to dissociate the two sources of dependencies. In the new augmented space, only one source of correlation remains directly related to the target parameters, the other sources of correlations being captured by the auxiliary variables. Experiments are conducted on two practical image restoration problems—namely the recovery of multichannel blurred images embedded in Gaussian noise and the recovery of signal corrupted by a mixed Gaussian noise. Experimental results indicate that adding the proposed auxiliary variables makes the sampling problem simpler since the new conditional distribution no longer contains highly heterogeneous

  16. The composite supply chain efficiency model: A case study of the Sishen-Saldanha supply chain

    Directory of Open Access Journals (Sweden)

    Leila L. Goedhals-Gerber

    2016-01-01

    Full Text Available As South Africa strives to be a major force in global markets, it is essential that South African supply chains achieve and maintain a competitive advantage. One approach to achieving this is to ensure that South African supply chains maximise their levels of efficiency. Consequently, the efficiency levels of South Africa’s supply chains must be evaluated. The objective of this article is to propose a model that can assist South African industries in becoming internationally competitive by providing them with a tool for evaluating their levels of efficiency both as individual firms and as a component in an overall supply chain. The Composite Supply Chain Efficiency Model (CSCEM was developed to measure supply chain efficiency across supply chains using variables identified as problem areas experienced by South African supply chains. The CSCEM is tested in this article using the Sishen-Saldanda iron ore supply chain as a case study. The results indicate that all three links or nodes along the Sishen-Saldanha iron ore supply chain performed well. The average efficiency of the rail leg was 97.34%, while the average efficiency of the mine and the port were 97% and 95.44%, respectively. The results also show that the CSCEM can be used by South African firms to measure their levels of supply chain efficiency. This article concludes with the benefits of the CSCEM.

  17. Stability of llama heavy chain antibody fragments under extreme conditions

    NARCIS (Netherlands)

    Dolk, E.

    2004-01-01

    Camelids have next to their normal antibodies, a unique subset of antibodies lacking light chains. The resulting single binding domain, VHH, of these heavy chain antibodies consequently have unique properties. A high stability is one of these properties, which was investigated in this thesis. The

  18. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  19. Fluorescent protein-mediated colour polymorphism in reef corals: multicopy genes extend the adaptation/acclimatization potential to variable light environments.

    Science.gov (United States)

    Gittins, John R; D'Angelo, Cecilia; Oswald, Franz; Edwards, Richard J; Wiedenmann, Jörg

    2015-01-01

    The genomic framework that enables corals to adjust to unfavourable conditions is crucial for coral reef survival in a rapidly changing climate. We have explored the striking intraspecific variability in the expression of coral pigments from the green fluorescent protein (GFP) family to elucidate the genomic basis for the plasticity of stress responses among reef corals. We show that multicopy genes can greatly increase the dynamic range over which corals can modulate transcript levels in response to the light environment. Using the red fluorescent protein amilFP597 in the coral Acropora millepora as a model, we demonstrate that its expression increases with light intensity, but both the minimal and maximal gene transcript levels vary markedly among colour morphs. The pigment concentration in the tissue of different morphs is strongly correlated with the number of gene copies with a particular promoter type. These findings indicate that colour polymorphism in reef corals can be caused by the environmentally regulated expression of multicopy genes. High-level expression of amilFP597 is correlated with reduced photodamage of zooxanthellae under acute light stress, supporting a photoprotective function of this pigment. The cluster of light-regulated pigment genes can enable corals to invest either in expensive high-level pigmentation, offering benefits under light stress, or to rely on low tissue pigment concentrations and use the conserved resources for other purposes, which is preferable in less light-exposed environments. The genomic framework described here allows corals to pursue different strategies to succeed in habitats with highly variable light stress levels. In summary, our results suggest that the intraspecific plasticity of reef corals' stress responses is larger than previously thought. © 2014 The Authors Molecular Ecology Published by John Wiley & Sons Ltd.

  20. Diagnostic value of immunoglobulin κ light chain gene rearrangement analysis in B-cell lymphomas.

    Science.gov (United States)

    Kokovic, Ira; Jezersek Novakovic, Barbara; Novakovic, Srdjan

    2015-03-01

    Analysis of the immunoglobulin κ light chain (IGK) gene is an alternative method for B-cell clonality assessment in the diagnosis of mature B-cell proliferations in which the detection of clonal immunoglobulin heavy chain (IGH) gene rearrangements fails. The aim of the present study was to evaluate the added value of standardized BIOMED-2 assay for the detection of clonal IGK gene rearrangements in the diagnostic setting of suspected B-cell lymphomas. With this purpose, 92 specimens from 80 patients with the final diagnosis of mature B-cell lymphoma (37 specimens), mature T-cell lymphoma (26 specimens) and reactive lymphoid proliferation (29 specimens) were analyzed for B-cell clonality. B-cell clonality analysis was performed using the BIOMED-2 IGH and IGK gene clonality assays. The determined sensitivity of the IGK assay was 67.6%, while the determined sensitivity of the IGH assay was 75.7%. The sensitivity of combined IGH+IGK assay was 81.1%. The determined specificity of the IGK assay was 96.2% in the group of T-cell lymphomas and 96.6% in the group of reactive lesions. The determined specificity of the IGH assay was 84.6% in the group of lymphomas and 86.2% in the group of reactive lesions. The comparison of GeneScan (GS) and heteroduplex pretreatment-polyacrylamide gel electrophoresis (HD-PAGE) methods for the analysis of IGK gene rearrangements showed a higher efficacy of GS analysis in a series of 27 B-cell lymphomas analyzed by both methods. In the present study, we demonstrated that by applying the combined IGH+IGK clonality assay the overall detection rate of B-cell clonality was increased by 5.4%. Thus, we confirmed the added value of the standardized BIOMED-2 IGK assay for assessment of B-cell clonality in suspected B-cell lymphomas with inconclusive clinical and cyto/histological diagnosis.

  1. Influence of an irregular surface and low light on the step variability of patients with peripheral neuropathy during level gait.

    Science.gov (United States)

    Thies, Sibylle B; Richardson, James K; Demott, Trina; Ashton-Miller, James A

    2005-08-01

    Patients with peripheral neuropathy (PN) report greater difficulty walking on irregular surfaces with low light (IL) than on flat surfaces with regular lighting (FR). We tested the primary hypothesis that older PN patients would demonstrate greater step width and step width variability under IL conditions than under FR conditions. Forty-two subjects (22 male, 20 female: mean +/- S.D.: 64.7 +/- 9.8 years) with PN underwent history, physical examination, and electrodiagnostic testing. Subjects were asked to walk 10 m at a comfortable speed while kinematic and force data were measured at 100 Hz using optoelectronic markers and foot switches. Ten trials were conducted under both IL and FR conditions. Step width, time, length, and speed were calculated with a MATLAB algorithm, with the standard deviation serving as the measure of variability. The results showed that under IL, as compared to FR, conditions subjects demonstrated greater step width (197.1 +/- 40.8 mm versus 180.5 +/- 32.4 mm; P < 0.001) and step width variability (40.4 +/- 9.0 mm versus 34.5 +/- 8.4 mm; P < 0.001), step time and its variability (P < 0.001 and P = 0.003, respectively), and step length variability (P < 0.001). Average step length and gait speed decreased under IL conditions (P < 0.001 for both). Step width variability and step time variability correlated best under IL conditions with a clinical measure of PN severity and fall history, respectively. We conclude that IL conditions cause PN patients to increase the variability of their step width and other gait parameters.

  2. Practical way to avoid spurious geometrical contributions in Brillouin light scattering experiments at variable scattering angles.

    Science.gov (United States)

    Battistoni, Andrea; Bencivenga, Filippo; Fioretto, Daniele; Masciovecchio, Claudio

    2014-10-15

    In this Letter, we present a simple method to avoid the well-known spurious contributions in the Brillouin light scattering (BLS) spectrum arising from the finite aperture of collection optics. The method relies on the use of special spatial filters able to select the scattered light with arbitrary precision around a given value of the momentum transfer (Q). We demonstrate the effectiveness of such filters by analyzing the BLS spectra of a reference sample as a function of scattering angle. This practical and inexpensive method could be an extremely useful tool to fully exploit the potentiality of Brillouin acoustic spectroscopy, as it will easily allow for effective Q-variable experiments with unparalleled luminosity and resolution.

  3. Resonance Assignments and Secondary Structure Analysis of Dynein Light Chain 8 by Magic-angle Spinning NMR Spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Shangjin; Butterworth, Andrew H.; Paramasivam, Sivakumar; Yan, Si; Lightcap, Christine M.; Williams, John C.; Polenova, Tatyana E.

    2011-08-04

    Dynein light chain LC8 is the smallest subunit of the dynein motor complex and has been shown to play important roles in both dynein-dependent and dynein-independent physiological functions via its interaction with a number of its binding partners. It has also been linked to pathogenesis including roles in viral infections and tumorigenesis. Structural information for LC8-target proteins is critical to understanding the underlying function of LC8 in these complexes. However, some LC8-target interactions are not amenable to structural characterization by conventional structural biology techniques owing to their large size, low solubility, and crystallization difficulties. Here, we report magic-angle spinning (MAS) NMR studies of the homodimeric apo-LC8 protein as a first effort in addressing more complex, multi-partner, LC8-based protein assemblies. We have established site-specific backbone and side-chain resonance assignments for the majority of the residues of LC8, and show TALOS+-predicted torsion angles ø and ψ in close agreement with most residues in the published LC8 crystal structure. Data obtained through these studies will provide the first step toward using MAS NMR to examine the LC8 structure, which will eventually be used to investigate protein–protein interactions in larger systems that cannot be determined by conventional structural studies.

  4. Immunoglobulin heavy and light chains and T-cell receptor beta and gamma chains PCR assessment on cytological samples. A study comparing FTA cards and cryopreserved lymph node fine-needle cytology.

    Science.gov (United States)

    Peluso, A L; Cozzolino, I; Bottiglieri, A; Lucchese, L; Di Crescenzo, R M; Langella, M; Selleri, C; Zeppa, P

    2017-06-01

    To evaluate and compare the DNA yield and quality extracted from lymph node fine needle cytology (FNC) samples stored on FTA cards to those cryopreserved, and to assess the immunoglobulin heavy and light chains (IGHK) and T-Cell receptor beta and gamma chains (TCRBG) PCR tests. DNA extractions were performed on FNC of 80 non-Hodgkin lymphomas (NHL), four myelomas and 56 benign reactive hyperplasias (BRH) cryopreserved and stored on FTA cards. The JAK2 gene was amplified to assess the DNA integrity and the IGHK/TCRBG clonality status was tested. IGHK monoclonality was found in 99% of B-cell NHL and 100% of myeloma. TCRBG monoclonality was found in 100% of T-cell NHL. TCRBG polyclonality was detected in 97% of B-cell NHL, 100% of myeloma and 96% of BRH. IGHK/TCRBG PCR data were confirmed by histological and/or follow-up controls. No differences were found in the DNA quality between cryopreservation and FTA cards storage methods. IGHK/TCRBG PCR of the lymphoproliferative process on FTA cards is comparable to those cryopreserved. FTA cards can be used to store lymph node FNC for further molecular investigations. © 2016 John Wiley & Sons Ltd.

  5. Crystallization and preliminary crystallographic studies of the single-chain variable fragment of antibody chA21 in complex with an N-terminal fragment of ErbB2

    International Nuclear Information System (INIS)

    Liu, Yang; Zhou, Huihao; Zhu, Juanjuan; Gao, Yongxiang; Niu, Liwen; Liu, Jing; Teng, Maikun

    2009-01-01

    An antibody–antigen complex consisting of a single-chain variable fragment of the potential therapeutic antibody chA21 and an N-terminal fragment (residues 1–192) of the human ErbB2 extracellular domain was expressed, purified and crystallized. X-ray diffraction data were collected to 2.45 Å resolution. ErbB2 is a transmembrane tyrosine kinase, the overexpression of which causes abnormality and disorder in cell signalling and leads to cell transformation. Previously, an anti-ErbB2 single-chain chimeric antibody chA21 that specifically inhibits the growth of ErbB2-overexpressing cancer cells in vitro and in vivo was developed. Here, an antibody–antigen complex consisting of the single-chain variable fragment (scFv) of chA21 and an N-terminal fragment (residues 1–192, named EP I) of the ErbB2 extracellular domain was crystallized using the sitting-drop vapour-diffusion method. An X-ray diffraction data set was collected to 2.45 Å resolution from a single flash-cooled crystal; the crystal belonged to space group P2 1 2 1 2 1

  6. Confocal Cornea Microscopy Detects Involvement of Corneal Nerve Fibers in a Patient with Light-Chain Amyloid Neuropathy Caused by Multiple Myeloma: A Case Report

    Directory of Open Access Journals (Sweden)

    Dietrich Sturm

    2016-06-01

    Full Text Available Changes in the subbasal corneal plexus detected by confocal cornea microscopy (CCM have been described for various types of neuropathy. An involvement of these nerves within light-chain (AL amyloid neuropathy (a rare cause of polyneuropathy has never been shown. Here, we report on a case of a patient suffering from neuropathy caused by AL amyloidosis and underlying multiple myeloma. Small-fiber damage was detected by CCM.

  7. Myosin light chain kinase mediates intestinal barrier disruption following burn injury.

    Directory of Open Access Journals (Sweden)

    Chuanli Chen

    Full Text Available BACKGROUND: Severe burn injury results in the loss of intestinal barrier function, however, the underlying mechanism remains unclear. Myosin light chain (MLC phosphorylation mediated by MLC kinase (MLCK is critical to the pathophysiological regulation of intestinal barrier function. We hypothesized that the MLCK-dependent MLC phosphorylation mediates the regulation of intestinal barrier function following burn injury, and that MLCK inhibition attenuates the burn-induced intestinal barrier disfunction. METHODOLOGY/PRINCIPAL FINDINGS: Male balb/c mice were assigned randomly to either sham burn (control or 30% total body surface area (TBSA full thickness burn without or with intraperitoneal injection of ML-9 (2 mg/kg, an MLCK inhibitor. In vivo intestinal permeability to fluorescein isothiocyanate (FITC-dextran was measured. Intestinal mucosa injury was assessed histologically. Tight junction proteins ZO-1, occludin and claudin-1 was analyzed by immunofluorescent assay. Expression of MLCK and phosphorylated MLC in ileal mucosa was assessed by Western blot. Intestinal permeability was increased significantly after burn injury, which was accompanied by mucosa injury, tight junction protein alterations, and increase of both MLCK and MLC phosphorylation. Treatment with ML-9 attenuated the burn-caused increase of intestinal permeability, mucosa injury, tight junction protein alterations, and decreased MLC phosphorylation, but not MLCK expression. CONCLUSIONS/SIGNIFICANCE: The MLCK-dependent MLC phosphorylation mediates intestinal epithelial barrier dysfunction after severe burn injury. It is suggested that MLCK-dependent MLC phosphorylation may be a critical target for the therapeutic treatment of intestinal epithelial barrier disruption after severe burn injury.

  8. Heavy chain only antibodies

    DEFF Research Database (Denmark)

    Moghimi, Seyed Moein; Rahbarizadeh, Fatemeh; Ahmadvand, Davoud

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen...

  9. Applying Markov Chains for NDVI Time Series Forecasting of Latvian Regions

    Directory of Open Access Journals (Sweden)

    Stepchenko Arthur

    2015-12-01

    Full Text Available Time series of earth observation based estimates of vegetation inform about variations in vegetation at the scale of Latvia. A vegetation index is an indicator that describes the amount of chlorophyll (the green mass and shows the relative density and health of vegetation. NDVI index is an important variable for vegetation forecasting and management of various problems, such as climate change monitoring, energy usage monitoring, managing the consumption of natural resources, agricultural productivity monitoring, drought monitoring and forest fire detection. In this paper, we make a one-step-ahead prediction of 7-daily time series of NDVI index using Markov chains. The choice of a Markov chain is due to the fact that a Markov chain is a sequence of random variables where each variable is located in some state. And a Markov chain contains probabilities of moving from one state to other.

  10. Light refraction in sapphire plates with a variable angle of crystal optical axis to the surface

    International Nuclear Information System (INIS)

    Vetrov, V. N.; Ignatenkov, B. A.

    2013-01-01

    The modification of sapphire by inhomogeneous plastic deformation makes it possible to obtain plates with a variable angle of inclination of the crystal optical axis to the plate surface. The refraction of light in this plate at perpendicular and oblique incidence of a parallel beam of rays is considered. The algorithm of calculating the refractive index of extraordinary ray and the birefringence is proposed.

  11. Size, shape, and diffusivity of a single Debye-Hückel polyelectrolyte chain in solution

    Science.gov (United States)

    Soysa, W. Chamath; Dünweg, B.; Prakash, J. Ravi

    2015-08-01

    Brownian dynamics simulations of a coarse-grained bead-spring chain model, with Debye-Hückel electrostatic interactions between the beads, are used to determine the root-mean-square end-to-end vector, the radius of gyration, and various shape functions (defined in terms of eigenvalues of the radius of gyration tensor) of a weakly charged polyelectrolyte chain in solution, in the limit of low polymer concentration. The long-time diffusivity is calculated from the mean square displacement of the centre of mass of the chain, with hydrodynamic interactions taken into account through the incorporation of the Rotne-Prager-Yamakawa tensor. Simulation results are interpreted in the light of the Odjik, Skolnick, Fixman, Khokhlov, and Khachaturian blob scaling theory (Everaers et al., Eur. Phys. J. E 8, 3 (2002)) which predicts that all solution properties are determined by just two scaling variables—the number of electrostatic blobs X and the reduced Debye screening length, Y. We identify three broad regimes, the ideal chain regime at small values of Y, the blob-pole regime at large values of Y, and the crossover regime at intermediate values of Y, within which the mean size, shape, and diffusivity exhibit characteristic behaviours. In particular, when simulation results are recast in terms of blob scaling variables, universal behaviour independent of the choice of bead-spring chain parameters, and the number of blobs X, is observed in the ideal chain regime and in much of the crossover regime, while the existence of logarithmic corrections to scaling in the blob-pole regime leads to non-universal behaviour.

  12. AEOLUS: A MARKOV CHAIN MONTE CARLO CODE FOR MAPPING ULTRACOOL ATMOSPHERES. AN APPLICATION ON JUPITER AND BROWN DWARF HST LIGHT CURVES

    Energy Technology Data Exchange (ETDEWEB)

    Karalidi, Theodora; Apai, Dániel; Schneider, Glenn; Hanson, Jake R. [Steward Observatory, Department of Astronomy, University of Arizona, 933 N. Cherry Avenue, Tucson, AZ 85721 (United States); Pasachoff, Jay M., E-mail: tkaralidi@email.arizona.edu [Hopkins Observatory, Williams College, 33 Lab Campus Drive, Williamstown, MA 01267 (United States)

    2015-11-20

    Deducing the cloud cover and its temporal evolution from the observed planetary spectra and phase curves can give us major insight into the atmospheric dynamics. In this paper, we present Aeolus, a Markov chain Monte Carlo code that maps the structure of brown dwarf and other ultracool atmospheres. We validated Aeolus on a set of unique Jupiter Hubble Space Telescope (HST) light curves. Aeolus accurately retrieves the properties of the major features of the Jovian atmosphere, such as the Great Red Spot and a major 5 μm hot spot. Aeolus is the first mapping code validated on actual observations of a giant planet over a full rotational period. For this study, we applied Aeolus to J- and H-band HST light curves of 2MASS J21392676+0220226 and 2MASS J0136565+093347. Aeolus retrieves three spots at the top of the atmosphere (per observational wavelength) of these two brown dwarfs, with a surface coverage of 21% ± 3% and 20.3% ± 1.5%, respectively. The Jupiter HST light curves will be publicly available via ADS/VIZIR.

  13. Measuring the influence of industry sector membership on supply chain disruption reporting.

    Science.gov (United States)

    Alcantara, Patrick

    2015-01-01

    The global Supply Chain Resilience Survey by the Business Continuity Institute and Zurich Insurance is a comprehensive study on the state of supply chains in different organisations worldwide. As a benchmarking tool, it also contains data about business continuity arrangements in place to ensure supply chain resilience. Given this study's historically qualitative approach to reporting, this paper aims to introduce quantitative analysis. In this paper, responses that report membership in Standard Industrial Classification 2007 industry sectors from the 2013 Supply Chain Resilience Survey were disaggregated and related to supply chain disruption reporting. A chi-square test of independence reveals that membership in a particular industry sector influences reporting of supply chain disruption. Nonetheless, the relationship between these variables is weak. This study demonstrates interesting differences between industry sectors in terms of supply chain resilience. Further research is required in terms of other variables in order to provide granularity and relevant findings to supply chain planners.

  14. Facilitators and Inhibitors of Supply Chain Innovation-prospects for Supply Chain Managment in the Irish Grocery Sector

    OpenAIRE

    Keegan, Joan; O'Callaghan, Edmund; Wilcox, Mary

    2001-01-01

    Supply chain management is one of the most significant strategic challenges currently facing the Irish grocery sector. The UK grocery market with its emphasis on composite deliveries via regional distribution centres is extremely sophisticated; the Irish grocery sector, however, is in the embryonic stage of implementing central distribution. The potential to develop innovative supply chain systems is mediated by both national logistic-related variables and company characteristics. In additio...

  15. 2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †.

    Science.gov (United States)

    Renz, Mark; Torres, Ronald; Dolan, Philip J; Tam, Stephen J; Tapia, Jose R; Li, Lauri; Salmans, Joshua R; Barbour, Robin M; Shughrue, Paul J; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G; Zago, Wagner

    2016-09-01

    Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency-approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T-positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis.

  16. 2A4 binds soluble and insoluble light chain aggregates from AL amyloidosis patients and promotes clearance of amyloid deposits by phagocytosis †

    Science.gov (United States)

    Renz, Mark; Torres, Ronald; Dolan, Philip J.; Tam, Stephen J.; Tapia, Jose R.; Li, Lauri; Salmans, Joshua R.; Barbour, Robin M.; Shughrue, Paul J.; Nijjar, Tarlochan; Schenk, Dale; Kinney, Gene G.; Zago, Wagner

    2016-01-01

    Abstract Amyloid light chain (AL) amyloidosis is characterized by misfolded light chain (LC) (amyloid) deposition in various peripheral organs, leading to progressive dysfunction and death. There are no regulatory agency–approved treatments for AL amyloidosis, and none of the available standard of care approaches directly targets the LC protein that constitutes the amyloid. NEOD001, currently in late-stage clinical trials, is a conformation-specific, anti-LC antibody designed to specifically target misfolded LC aggregates and promote phagocytic clearance of AL amyloid deposits. The present study demonstrated that the monoclonal antibody 2A4, the murine form of NEOD001, binds to patient-derived soluble and insoluble LC aggregates and induces phagocytic clearance of AL amyloid in vitro. 2A4 specifically labeled all 21 fresh-frozen organ samples studied, which were derived from 10 patients representing both κ and λ LC amyloidosis subtypes. 2A4 immunoreactivity largely overlapped with thioflavin T–positive labeling, and 2A4 bound both soluble and insoluble LC aggregates extracted from patient tissue. Finally, 2A4 induced macrophage engagement and phagocytic clearance of AL amyloid deposits in vitro. These findings provide further evidence that 2A4/NEOD001 can effectively clear and remove human AL-amyloid from tissue and further support the rationale for the evaluation of NEOD001 in patients with AL amyloidosis. PMID:27494229

  17. Changes in the structure of calmodulin induced by a peptide based on the calmodulin-binding domain of myosin light chain kinase

    International Nuclear Information System (INIS)

    Heidorn, D.B.; Seeger, P.A.; Rokop, S.E.; Blumenthal, D.K.; Means, A.R.; Crespi, H.; Trewhella, J.

    1989-01-01

    Small-angle X-ray and neutron scattering data were used to study the solution structure of calmodulin complexed with a synthetic peptide corresponding to residues 577-603 of rabbit skeletal muscle myosin light chain kinase. The X-ray data indicate that, in the presence of Ca 2+ , the calmodulin-peptide complex has a structure that is considerably more compact than uncomplexed calmodulin. The radius of gyration, R g , for the complex is approximately 20% smaller than that of uncomplexed Ca 2+ ·calmodulin, and the maximum dimension, d max , for the complex is also about 20% smaller. The peptide-induced conformational rearrangement of calmodulin is [Ca 2+ ] dependent. The length distribution function for the complex is more symmetric than that for uncomplexed Ca 2+ ·calmodulin, indicating that more of the mass is distributed toward the center of mass for the complex, compared with the dumbbell-shaped Ca 2+ ·calmodulin. The solvent contrast dependence of R g for neutron scattering indicates that the peptide is located more toward the center of the complex, while the calmodulin is located more peripherally, and that the centers of mass of the calmodulin and the peptide are not coincident. The scattering data support the hypothesis that the interconnecting helix region observed in the crystal structure for calmodulin is quite flexible in solution, allowing the two lobes of calmodulin to form close contacts on binding the peptide. This flexibility of the central helix may play a critical role in activating target enzymes such as myosin light chain kinase

  18. Phenotypic plasticity of mesenchymal stem cells is crucial for mesangial repair in a model of immunoglobulin light chain-associated mesangial damage.

    Science.gov (United States)

    Herrera, Guillermo A; Teng, Jiamin; Zeng, Chun; Xu, Hongzhi; Liang, Man; Alexander, J Steven; Liu, Bing; Boyer, Chris; Turbat-Herrera, Elba A

    2018-01-01

    Mesangiopathies produced by glomerulopathic monoclonal immunoglobulin light chains (GLCs) acting on the glomerular mesangium produce two characteristic lesions: AL-amyloidosis (AL-Am) and light chain deposition disease (LCDD). In both cases, the pathology is centered in the mesangium, where initial and progressive damage occurs. In AL-Am the mesangial matrix is destroyed and replaced by amyloid fibrils and in LCDD, the mesangial matrix is increased and remodeled. The collagen IV rich matrix is replaced by tenascin. In both conditions, mesangial cells (MCs) become apoptotic as a direct effect of the GLCs. MCs were incubated in-vitro with GLCs and animal kidneys were perfused ex-vivo via the renal artery with GLCs, producing expected lesions, and then mesenchymal stem cells (MSCs) were added to both platforms. Each of the two platforms provided unique information that when put together created a comprehensive evaluation of the processes involved. A "cocktail" with growth and differentiating factors was used to study its effect on mesangial repair. MSCs displayed remarkable phenotypic plasticity during the repair process. The first role of the MSCs after migrating to the affected areas was to dispose of the amyloid fibrils (in AL-Am), the altered mesangial matrix (in LCDD) and apoptotic MCs/debris. To accomplish this task, MSCs transformed into facultative macrophages acquiring an abundance of lysosomes and endocytotic capabilities required to engage in phagocytic functions. Once the mesangial cleaning was completed, MSCs transformed into functional MCs restoring the mesangium to normal. "Cocktail" made the repair process more efficient.

  19. Quantifying Short-Chain Chlorinated Paraffin Congener Groups.

    Science.gov (United States)

    Yuan, Bo; Bogdal, Christian; Berger, Urs; MacLeod, Matthew; Gebbink, Wouter A; Alsberg, Tomas; de Wit, Cynthia A

    2017-09-19

    Accurate quantification of short-chain chlorinated paraffins (SCCPs) poses an exceptional challenge to analytical chemists. SCCPs are complex mixtures of chlorinated alkanes with variable chain length and chlorination level; congeners with a fixed chain length (n) and number of chlorines (m) are referred to as a "congener group" C n Cl m . Recently, we resolved individual C n Cl m by mathematically deconvolving soft ionization high-resolution mass spectra of SCCP mixtures. Here we extend the method to quantifying C n Cl m by introducing C n Cl m specific response factors (RFs) that are calculated from 17 SCCP chain-length standards with a single carbon chain length and variable chlorination level. The signal pattern of each standard is measured on APCI-QTOF-MS. RFs of each C n Cl m are obtained by pairwise optimization of the normal distribution's fit to the signal patterns of the 17 chain-length standards. The method was verified by quantifying SCCP technical mixtures and spiked environmental samples with accuracies of 82-123% and 76-109%, respectively. The absolute differences between calculated and manufacturer-reported chlorination degrees were -0.9 to 1.0%Cl for SCCP mixtures of 49-71%Cl. The quantification method has been replicated with ECNI magnetic sector MS and ECNI-Q-Orbitrap-MS. C n Cl m concentrations determined with the three instruments were highly correlated (R 2 > 0.90) with each other.

  20. Regulation of myosin light chain kinase during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Shelly Woody

    Full Text Available Myosin II (MyoII is required for insulin-responsive glucose transporter 4 (GLUT4-mediated glucose uptake in 3T3-L1 adipocytes. Our previous studies have shown that insulin signaling stimulates phosphorylation of the regulatory light chain (RLC of MyoIIA via myosin light chain kinase (MLCK. The experiments described here delineate upstream regulators of MLCK during insulin-stimulated glucose uptake. Since 3T3-L1 adipocytes express two MyoII isoforms, we wanted to determine which isoform was required for insulin-stimulated glucose uptake. Using a siRNA approach, we demonstrate that a 60% decrease in MyoIIA protein expression resulted in a 40% inhibition of insulin-stimulated glucose uptake. We also show that insulin signaling stimulates the phosphorylation of MLCK. We further show that MLCK can be activated by calcium as well as signaling pathways. We demonstrate that adipocytes treated with the calcium chelating agent, 1,2-b (iso-aminophenoxy ethane-N,N,N',N'-tetra acetic acid, (BAPTA (in the presence of insulin impaired the insulin-induced phosphorylation of MLCK by 52% and the RLC of MyoIIA by 45% as well as impairing the recruitment of MyoIIA to the plasma membrane when compared to cells treated with insulin alone. We further show that the calcium ionophore, A23187 alone stimulated the phosphorylation of MLCK and the RLC associated with MyoIIA to the same extent as insulin. To identify signaling pathways that might regulate MLCK, we examined ERK and CaMKII. Inhibition of ERK2 impaired phosphorylation of MLCK and insulin-stimulated glucose uptake. In contrast, while inhibition of CaMKII did inhibit phosphorylation of the RLC associated with MyoIIA, inhibition of CAMKIIδ did not impair MLCK phosphorylation or translocation to the plasma membrane or glucose uptake. Collectively, our results are the first to delineate a role for calcium and ERK in the activation of MLCK and thus MyoIIA during insulin-stimulated glucose uptake in 3T3-L1 adipocytes.

  1. Promoting occupational safety and health through the supply chain Literature review

    NARCIS (Netherlands)

    Ustailieva, E.; Starren, A.; Eeckelaert, L.; Lopes Nunes, I.; Hauke, A.

    2012-01-01

    This report sheds light on occupational safety and health (OSH) within complex supply chain networks. Based on a literature, policy and case study review it attempts to give an overview of how OSH can be managed and promoted through the supply chain, and which drivers, incentives and instruments

  2. Motivators to Adopt Green Supply Chain Initiatives

    OpenAIRE

    Amarpreet S. Kohli; Ellen Hawkins

    2015-01-01

    There are several factors that drive organizations to consider implementing green supply chain (GSC) initiatives. This paper refines an instrument to empirically test the significance of the following drivers for participation in GSC initiatives: Government Regulation, Buyer/Supply Chain Influence, Internal Readiness, Competitive Advantage, and Corporate Social Responsibility. Corporate Social Responsibility emerged as the most significant variable that effected the decision making of the org...

  3. SUPPLY CHAIN RISKS: LITERATURE REVIEW AND A NEW CATEGORIZATION

    OpenAIRE

    Er Kara, Merve; Oktay Fırat, Seniye Ümit

    2017-01-01

    Identification of risks is the first step to build a resilient and sustainable supply chain and develop proactive risk management strategies. Supply chains contain numerous risks with different forms, probabilities and impacts. Supply chain risks have a multi-dimensional nature and can result from a wide variety of sources including demand and supply variability, poor performing suppliers, price fluctuations, dynamic consumer markets, global economic uncertainty, and even unexpected events su...

  4. The Vulnerability of Rice Value Chains in Sub-Saharan Africa: A Review

    Directory of Open Access Journals (Sweden)

    Fanen Terdoo

    2016-09-01

    Full Text Available Rice is one of the most important food crops in sub-Saharan Africa. Climate change, variability, and economic globalization threatens to disrupt rice value chains across the subcontinent, undermining their important role in economic development, food security, and poverty reduction. This paper maps existing research on the vulnerability of rice value chains, synthesizes the evidence and the risks posed by climate change and economic globalization, and discusses agriculture and rural development policies and their relevance for the vulnerability of rice value chains in sub-Saharan Africa. Important avenues for future research are identified. These include the impacts of multiple, simultaneous pressures on rice value chains, the effects of climate change and variability on parts of the value chain other than production, and the forms and extent to which different development policies hinder or enhance the resilience of rice value chains in the face of climatic and other pressures.

  5. Image compensation for camera and lighting variability

    Science.gov (United States)

    Daley, Wayne D.; Britton, Douglas F.

    1996-12-01

    With the current trend of integrating machine vision systems in industrial manufacturing and inspection applications comes the issue of camera and illumination stabilization. Unless each application is built around a particular camera and highly controlled lighting environment, the interchangeability of cameras of fluctuations in lighting become a problem as each camera usually has a different response. An empirical approach is proposed where color tile data is acquired using the camera of interest, and a mapping is developed to some predetermined reference image using neural networks. A similar analytical approach based on a rough analysis of the imaging systems is also considered for deriving a mapping between cameras. Once a mapping has been determined, all data from one camera is mapped to correspond to the images of the other prior to performing any processing on the data. Instead of writing separate image processing algorithms for the particular image data being received, the image data is adjusted based on each particular camera and lighting situation. All that is required when swapping cameras is the new mapping for the camera being inserted. The image processing algorithms can remain the same as the input data has been adjusted appropriately. The results of utilizing this technique are presented for an inspection application.

  6. A tactical supply chain planning model with multiple flexibility options

    DEFF Research Database (Denmark)

    Esmaeilikia, Masoud; Fahimnia, Behnam; Sarkis, Joeseph

    2016-01-01

    Supply chain flexibility is widely recognized as an approach to manage uncertainty. Uncertainty in the supply chain may arise from a number of sources such as demand and supply interruptions and lead time variability. A tactical supply chain planning model with multiple flexibility options...... incorporated in sourcing, manufacturing and logistics functions can be used for the analysis of flexibility adjustment in an existing supply chain. This paper develops such a tactical supply chain planning model incorporating a realistic range of flexibility options. A novel solution method is designed...

  7. Light induced intraspecific variability in response to thermal stress in the hard coral Stylophora pistillata

    Directory of Open Access Journals (Sweden)

    Arjen Tilstra

    2017-10-01

    Full Text Available Recent research suggests that prior exposure of several months to elevated irradiance induces enhanced thermal tolerance in scleractinian corals. While this tolerance has been reported at the species level, individual coral colonies may react differently due to individual variability in thermal tolerance. As thermal anomalies are predicted to become common in the upcoming future, intraspecific variation may be key to the survival of coral populations. In order to study light-history based thermal stress responses on individual colonies, we developed a preliminary microcosm experiment where three randomly chosen, aquacultured colonies of the model coral Stylophora pistillata were exposed to two irradiance treatments (200 and 400 μmol photons m−2 s−1 for 31 days, followed by artificially induced heat stress (∼33.4 °C. We found different responses to occur at both the intraspecific and the intracolonial levels, as indicated by either equal, less severe, delayed, and/or even non-necrotic responses of corals previously exposed to the irradiance of 400 compared to 200 μmol photons m−2 s−1. In addition, all individual colonies revealed light-enhanced calcification. Finally, elevated irradiance resulted in a lower chlorophyll a concentration in one colony compared to the control treatment, and the same colony displayed more rapid bleaching compared to the other ones. Taken together, this study highlights the potential importance of intra-individual variability in physiological responses of scleractinian corals and provides recommendations for improving methodological designs for future studies.

  8. Exploring single chain amphiphile self-assembly and their possible roles in light transduction

    DEFF Research Database (Denmark)

    Monnard, Pierre-Alain

    2011-01-01

    Self-assembled structures of single-chain amphiphiles have been used as hosts for biochemical, and chemical reactions. Their use as models for protocells (i.e., precursors to the first biological cells) has been extensively researched by various groups because the availability of single chain......: the medium composition in terms of ionic strengths and the medium physical parameters, such as temperature, significantly influence the formation of structures, as well as their subsequent stability. In addition, membranes composed of a single amphiphile type seem to be implausible as no potential amphiphile...... source studied to date can supply one single type of amphiphile at concentrations conducive to self-assembly. Mixtures of single-chain amphiphiles were therefore proposed to better model primitive membranes and potentially enhance their structural integrity1-3. Recently, we have established that complex...

  9. Spin chains and Gustafson's integrals

    International Nuclear Information System (INIS)

    Derkachov, S.E; Manashov, A.N.; Regensburg Univ.

    2016-12-01

    The Gustafson's integrals are the multidimensional generalization of the classical Mellin-Barnes integrals. We show that some of these integrals arise from relations between matrix elements in the Sklyanin's representation of Separated Variables in the spin chain models. We also present several new integrals.

  10. Spatial and temporal variability of canopy cover and understory light in a Cerrado of Southern Brazil

    Directory of Open Access Journals (Sweden)

    JP. Lemos-Filho

    Full Text Available Canopy cover has significant effects on the understory environment, including upon light availability for seedling growth. The aim of the present study was to verify spatial heterogeneity and seasonal changes in the canopy cover of a dense Cerrado area, and their relationship to understory photosynthetic active radiation availability. Leaf area index (LAI values in the rainy season varied from 0.9 to 4.83, with 40% of the values ranging from 4.0 to 5.0, while in the dry season LAI varied from 0.74 to 3.3, with 53% of the values oscilating from 2.0 to 3.0. Understory light (Qi and the Lambert-Beer ratio (Qi/Qo were taken around noon on sunny days (between 11:00 AM and 1:00 PM. They were also statistically different (p < 0.01 between the dry and wet seasons, with 72% of sampled points in the rainy season presenting photosynthetic photon flux density (PPFD values lower than 250 μmol.m-2/s around noon, whereas in the dry season, most PPFD values varied from 1500 to 1817 μmol.m-2/s , thus providing high light availability for understory plants. In most of the studied sites, understory plants did not even receive enough light for 50% of their photosynthetic capacity in the wet season. In contrast during the dry season, Qi/Qo values of 0.8 to 1.0 were observed in more than 50% of the points, thereby allowing for photosynthetic light saturation. Thus, light variability around noon was higher during the dry season than in the wet season, its heterogeneity being related to spatial complexity in the canopy cover.

  11. A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin G1.

    Science.gov (United States)

    De Nardis, Camilla; Hendriks, Linda J A; Poirier, Emilie; Arvinte, Tudor; Gros, Piet; Bakker, Alexander B H; de Kruif, John

    2017-09-01

    Bispecific antibodies combine two different antigen-binding sites in a single molecule, enabling more specific targeting, novel mechanisms of action, and higher clinical efficacies. Although they have the potential to outperform conventional monoclonal antibodies, many bispecific antibodies have issues regarding production, stability, and pharmacokinetic properties. Here, we describe a new approach for generating bispecific antibodies using a common light chain format and exploiting the stable architecture of human immunoglobulin G 1 We used iterative experimental validation and computational modeling to identify multiple Fc variant pairs that drive efficient heterodimerization of the antibody heavy chains. Accelerated stability studies enabled selection of one Fc variant pair dubbed "DEKK" consisting of substitutions L351D and L368E in one heavy chain combined with L351K and T366K in the other. Solving the crystal structure of the DEKK Fc region at a resolution of 2.3 Å enabled detailed analysis of the interactions inducing CH3 interface heterodimerization. Local shifts in the IgG backbone accommodate the introduction of lysine side chains that form stabilizing salt-bridge interactions with substituted and native residues in the opposite chain. Overall, the CH3 domain adapted to these shifts at the interface, yielding a stable Fc conformation very similar to that in wild-type IgG. Using the DEKK format, we generated the bispecific antibody MCLA-128, targeting human EGF receptors 2 and 3. MCLA-128 could be readily produced and purified at industrial scale with a standard mammalian cell culture platform and a routine purification protocol. Long-term accelerated stability assays confirmed that MCLA-128 is highly stable and has excellent biophysical characteristics. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  12. Reverse logistics and closed-loop supply chain

    DEFF Research Database (Denmark)

    Govindan, Kannan; Soleimani, Hamed; Kannan, Devika

    2015-01-01

    Based on environmental, legal, social, and economic factors, reverse logistics and closed-loop supply chain issues have attracted attention among both academia and practitioners. This attention is evident by the vast number of publications in scientific journals which have been published in recent...... years. Hence, a comprehensive literature review of recent and state-of-the-art papers is vital to draw a framework of the past, and to shed light on future directions. The aim of this paper is to review recently published papers in reverse logistic and closed-loop supply chain in scientific journals...

  13. CSF neurofilament light chain but not FLT3 ligand discriminates Parkinsonian disorders

    Directory of Open Access Journals (Sweden)

    Megan Kristy Herbert

    2015-05-01

    Full Text Available The differentiation between multiple system atrophy (MSA and Parkinson’s disease (PD is difficult, particularly in early disease stages. Therefore, we aimed to evaluate the diagnostic value of neurofilament light chain (NFL, fms-like tyrosine kinase ligand (FLT3L and total tau protein (t-tau in cerebrospinal fluid (CSF as biomarkers to discriminate MSA from PD. Using commercially available enzyme-linked immunoassays (ELISAs, we measured CSF levels of NFL, FLT3L and t-tau in a discovery cohort of 36 PD patients, 27 MSA patients and 57 non-neurological controls and in a validation cohort of 32 PD patients, 25 MSA patients, 15 PSP patients, 5 CBS patients, and 56 non-neurological controls. Cut-offs obtained from individual assays and binary logistic regression models developed from combinations of biomarkers were assessed. CSF levels of NFL were substantially increased in MSA and discriminated between MSA and PD with a sensitivity of 74% and specificity of 92% (AUC = 0.85 in the discovery cohort and with 80% sensitivity and 97% specificity (AUC = 0.94 in the validation cohort. FLT3L levels in CSF were significantly lower in both PD and MSA compared to controls in the discovery cohort, but not in the validation cohort. T-tau levels were significantly higher in MSA than PD and controls. Addition of either FLT3L or t-tau to NFL did not improve discrimination of PD from MSA above NFL alone. Our findings show that increased levels of NFL in CSF offer clinically relevant, high accuracy discrimination between PD and MSA.

  14. Designing of an artificial light energy converter in the form of short-chain dyad when combined with core-shell gold/silver nanocomposites.

    Science.gov (United States)

    Dutta Pal, Gopa; Paul, Somnath; Bardhan, Munmun; De, Asish; Ganguly, Tapan

    2017-06-05

    UV-vis absorption, steady state and time resolved fluorescence and absorption spectroscopic investigations demonstrate that the short chain dyad MNTMA when combined with gold-silver core-shell (Au@Ag) nanocomposite , forms elongated conformers in the excited state whereas for the dyad - Ag (spherical) system the majority of dyads remains in a folded conformation. In the dyad-core-shell nanocomposite system, energy wasting charge recombination rate slows down primarily due to elongated conformation and thus it may be anticipated that this hybrid nanocomposite system may serve as a better light energy conversion device. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Behavioral and other phenotypes in a cytoplasmic Dynein light intermediate chain 1 mutant mouse.

    Science.gov (United States)

    Banks, Gareth T; Haas, Matilda A; Line, Samantha; Shepherd, Hazel L; Alqatari, Mona; Stewart, Sammy; Rishal, Ida; Philpott, Amelia; Kalmar, Bernadett; Kuta, Anna; Groves, Michael; Parkinson, Nicholas; Acevedo-Arozena, Abraham; Brandner, Sebastian; Bannerman, David; Greensmith, Linda; Hafezparast, Majid; Koltzenburg, Martin; Deacon, Robert; Fainzilber, Mike; Fisher, Elizabeth M C

    2011-04-06

    The cytoplasmic dynein complex is fundamentally important to all eukaryotic cells for transporting a variety of essential cargoes along microtubules within the cell. This complex also plays more specialized roles in neurons. The complex consists of 11 types of protein that interact with each other and with external adaptors, regulators and cargoes. Despite the importance of the cytoplasmic dynein complex, we know comparatively little of the roles of each component protein, and in mammals few mutants exist that allow us to explore the effects of defects in dynein-controlled processes in the context of the whole organism. Here we have taken a genotype-driven approach in mouse (Mus musculus) to analyze the role of one subunit, the dynein light intermediate chain 1 (Dync1li1). We find that, surprisingly, an N235Y point mutation in this protein results in altered neuronal development, as shown from in vivo studies in the developing cortex, and analyses of electrophysiological function. Moreover, mutant mice display increased anxiety, thus linking dynein functions to a behavioral phenotype in mammals for the first time. These results demonstrate the important role that dynein-controlled processes play in the correct development and function of the mammalian nervous system.

  16. Logistic indicators measurement in two assembly operations feeded by supply-chains

    Directory of Open Access Journals (Sweden)

    Thiago Morais Menezes

    2008-07-01

    Full Text Available This paper presents a methodology for the measurement of logistic indicators. The methodology was applied in two cases: a shoewear assembling manufacture and a air conditioning assembling operation, both feeded by supply-chains. The study of the assembling operation can be useful in synchronizing the supply-chain and reducing variability in order arrivals by forming an assembly buffer. The methodology applies quantitative and graphic analysis to evaluate leadtime, inventory, performance and buffer. The first case was an exploration of the model, testing and refine its quantitative part. The second case, more extended, studied, in quantitative and graphically modes, two serial processes: standard assembling of items delivered by a supply-chain and customized services. The case was discussed and the implications analyzed. With the so calculated indicators, we suggest inventory reduction in assembling and increase in customization, so the total leadtime can also be reduced. Key words:, Logistic indicators, Queues in manufacture, Manufacturing Control; Variability in Supply Chains, Supply Chain management.

  17. Prognostics for Steam Generator Tube Rupture using Markov Chain model

    International Nuclear Information System (INIS)

    Kim, Gibeom; Heo, Gyunyoung; Kim, Hyeonmin

    2016-01-01

    This paper will describe the prognostics method for evaluating and forecasting the ageing effect and demonstrate the procedure of prognostics for the Steam Generator Tube Rupture (SGTR) accident. Authors will propose the data-driven method so called MCMC (Markov Chain Monte Carlo) which is preferred to the physical-model method in terms of flexibility and availability. Degradation data is represented as growth of burst probability over time. Markov chain model is performed based on transition probability of state. And the state must be discrete variable. Therefore, burst probability that is continuous variable have to be changed into discrete variable to apply Markov chain model to the degradation data. The Markov chain model which is one of prognostics methods was described and the pilot demonstration for a SGTR accident was performed as a case study. The Markov chain model is strong since it is possible to be performed without physical models as long as enough data are available. However, in the case of the discrete Markov chain used in this study, there must be loss of information while the given data is discretized and assigned to the finite number of states. In this process, original information might not be reflected on prediction sufficiently. This should be noted as the limitation of discrete models. Now we will be studying on other prognostics methods such as GPM (General Path Model) which is also data-driven method as well as the particle filer which belongs to physical-model method and conducting comparison analysis

  18. Evidence for Ig Light Chain Isotype Exclusion in Shark B Lymphocytes Suggests Ordered Mechanisms.

    Science.gov (United States)

    Iacoangeli, Anna; Lui, Anita; Haines, Ashley; Ohta, Yuko; Flajnik, Martin; Hsu, Ellen

    2017-09-01

    Unlike most vertebrates, the shark IgL gene organization precludes secondary rearrangements that delete self-reactive VJ rearranged genes. Nurse sharks express four L chain isotypes, κ, λ, σ, and σ-2, encoded by 35 functional minigenes or clusters. The sequence of gene activation/expression and receptor editing of these isotypes have not been studied. We therefore investigated the extent of isotypic exclusion in separated B cell subpopulations. Surface Ig (sIg)κ-expressing cells, isolated with mAb LK14 that recognizes Cκ, carry predominantly nonproductive rearrangements of other L chain isotypes. Conversely, after depletion with LK14, sIgM + cells contained largely nonproductive κ and enrichment for in-frame VJ of the others. Because some isotypic inclusion was observed at the mRNA level, expression in the BCR was examined. Functional λ mRNA was obtained, as expected, from the LK14-depleted population, but was also in sIgκ + splenocytes. Whereas λ somatic mutants from the depleted sample displayed evidence of positive selection, the λ genes in sIgκ + cells accumulated bystander mutations indicating a failure to express their products at the cell surface in association with the BCR H chain. In conclusion, a shark B cell expresses one L chain isotype at the surface and other isotypes as nonproductive VJ, sterile transcripts, or in-frame VJ whose products may not associate with the H chain. Based on the mRNA content found in the B cell subpopulations, an order of L chain gene activation is suggested as: σ-2 followed by κ, then σ and λ. Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Variable self-powered light detection CMOS chip with real-time adaptive tracking digital output based on a novel on-chip sensor.

    Science.gov (United States)

    Wang, HongYi; Fan, Youyou; Lu, Zhijian; Luo, Tao; Fu, Houqiang; Song, Hongjiang; Zhao, Yuji; Christen, Jennifer Blain

    2017-10-02

    This paper provides a solution for a self-powered light direction detection with digitized output. Light direction sensors, energy harvesting photodiodes, real-time adaptive tracking digital output unit and other necessary circuits are integrated on a single chip based on a standard 0.18 µm CMOS process. Light direction sensors proposed have an accuracy of 1.8 degree over a 120 degree range. In order to improve the accuracy, a compensation circuit is presented for photodiodes' forward currents. The actual measurement precision of output is approximately 7 ENOB. Besides that, an adaptive under voltage protection circuit is designed for variable supply power which may undulate with temperature and process.

  20. Contribution of components of Green Supply Chain Execution-Supply Loops in Green Supply Chain Performance measurement-A Pilot Empirical Study of the Indian Automobile Manufacturing Sector

    OpenAIRE

    Mohd. Asif Gandhi

    2017-01-01

    This paper is one of the several extensions of the research works done by [5]. Green Supply Chain Practices have been known to have an impact on Green Supply Chain Performance [5].This paper tests empirically through a pilot study of the Indian Automobile Manufacturing Sector, the contribution of the three variables constituting the construct Green Supply Chain Execution-Supply Loops in Green Supply Chain Performance measurement. Also the paper establishes the reliability of the questionnaire...

  1. On Darboux-integrable semi-discrete chains

    International Nuclear Information System (INIS)

    Habibullin, Ismagil; Sakieva, Alfia; Zheltukhina, Natalya

    2010-01-01

    A differential-difference equation d/dx t (n+1,x) = f(x,t(n,x),t(n+1,x),d/dx t (n,x)) with unknown t(n, x) depending on the continuous and discrete variables x and n is studied. We call an equation of such kind Darboux integrable if there exist two functions (called integrals) F and I of a finite number of dynamical variables such that D x F = 0 and DI = I, where D x is the operator of total differentiation with respect to x and D is the shift operator: Dp(n) = p(n + 1). It is proved that the integrals can be brought to some canonical form. A method of construction of an explicit formula for a general solution to Darboux-integrable chains is discussed and such solutions are found for a class of chains.

  2. Supply chain integration framework using literature review

    OpenAIRE

    Alfalla-Luque, Rafaela; Medina-Lopez, Carmen; Dey, Prasanta K.

    2013-01-01

    Definitions and measures of supply chain integration (SCI) are diverse. More empirical research, with clear definition and appropriate measures are needed. The purpose of this article is to identify dimensions and variables for SCI and develop an integrated framework to facilitate this. A literature review of the relevant academic papers in international journals in Logistics, Supply Chain Management and Operations Management for the period 1995-2009 has been undertaken. This study reveals th...

  3. The force dependence of isometric and concentric potentiation in mouse muscle with and without skeletal myosin light chain kinase.

    Science.gov (United States)

    Gittings, William; Aggarwal, Harish; Stull, James T; Vandenboom, Rene

    2015-01-01

    The isometric potentiation associated with myosin phosphorylation is force dependent. The purpose of this study was to assess the influence of a pre-existing period of isometric force on the concentric force potentiation displayed by mouse muscles with and without the ability to phosphorylate myosin. We tested isometric (ISO) and concentric (CON) potentiation, as well as concentric potentiation after isometric force (ISO-CON), in muscles from wild-type (WT) and skeletal myosin light chain kinase-deficient (skMLCK(-/-)) mice. A conditioning stimulus increased (i.e., potentiated) mean concentric force in the ISO-CON and CON conditions to 1.31 ± 0.02 and 1.35 ± 0.02 (WT) and to 1.19 ± 0.02 and 1.21 ± 0.01 (skMLCK(-/-)) of prestimulus levels, respectively (data n = 6-8, p muscles.

  4. Flexibility evaluation of multiechelon supply chains.

    Science.gov (United States)

    Almeida, João Flávio de Freitas; Conceição, Samuel Vieira; Pinto, Luiz Ricardo; de Camargo, Ricardo Saraiva; Júnior, Gilberto de Miranda

    2018-01-01

    Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution.

  5. Generation of high-affinity, internalizing anti-FGFR2 single-chain variable antibody fragment fused with Fc for targeting gastrointestinal cancers.

    Science.gov (United States)

    Borek, Aleksandra; Sokolowska-Wedzina, Aleksandra; Chodaczek, Grzegorz; Otlewski, Jacek

    2018-01-01

    Fibroblast growth factor receptors (FGFRs) are promising targets for antibody-based cancer therapies, as their substantial overexpression has been found in various tumor cells. Aberrant activation of FGF receptor 2 (FGFR2) signaling through overexpression of FGFR2 and/or its ligands, mutations, or receptor amplification has been reported in multiple cancer types, including gastric, colorectal, endometrial, ovarian, breast and lung cancer. In this paper, we describe application of the phage display technology to produce a panel of high affinity single chain variable antibody fragments (scFvs) against the extracellular ligand-binding domain of FGFR2 (ECD_FGFR2). The binders were selected from the human single chain variable fragment scFv phage display libraries Tomlinson I + J and showed high specificity and binding affinity towards human FGFR2 with nanomolar KD values. To improve the affinity of the best binder selected, scFvF7, we reformatted it to a bivalent diabody format, or fused it with the Fc region (scFvF7-Fc). The scFvF7-Fc antibody construct presented the highest affinity for FGFR2, with a KD of 0.76 nM, and was selectively internalized into cancer cells overexpressing FGFR2, Snu-16 and NCI-H716. Finally, we prepared a conjugate of scFvF7-Fc with the cytotoxic drug monomethyl-auristatin E (MMAE) and evaluated its cytotoxicity. The conjugate delivered MMAE selectively to FGFR2-positive tumor cells. These results indicate that scFvF7-Fc-vcMMAE is a highly potent molecule for the treatment of cancers with FGFR2 overexpression.

  6. Issue in Information Sharing of Halal Food Supply Chain

    Directory of Open Access Journals (Sweden)

    Masrom Nor Ratna

    2017-01-01

    Full Text Available Information sharing serves as an essential approach for the companies and antecedents of supply chain integration. Nowadays, with the highly competitive in halal food market, information sharing has become more conceivable. Furthermore, information sharing in supply chains has become more efficient by having meaningful relationship with the members of halal supply chain. There is a lack information regarding information shared within members in halal food supply chain literature. The information needed in order to shed the light of how companies nowadays can be more competitive. The purpose of this study is to investigate to what extent the information can be shared among the members of the halal food supply chain. This study elaborates the barriers of information sharing leading to enhanced supply chain integration among enterprises, as a result. The interview with four managers from halal certified food manufactures has been deployed to get rich data about the information sharing. The finding shows that most of cases halal certified food manufacturers has low communication with their suppliers. Trust is the key enablers within the members of halal food supply chain.

  7. Affinity maturation in an HIV broadly neutralizing B-cell lineage through reorientation of variable domains.

    Science.gov (United States)

    Fera, Daniela; Schmidt, Aaron G; Haynes, Barton F; Gao, Feng; Liao, Hua-Xin; Kepler, Thomas B; Harrison, Stephen C

    2014-07-15

    Rapidly evolving pathogens, such as human immunodeficiency and influenza viruses, escape immune defenses provided by most vaccine-induced antibodies. Proposed strategies to elicit broadly neutralizing antibodies require a deeper understanding of antibody affinity maturation and evolution of the immune response to vaccination or infection. In HIV-infected individuals, viruses and B cells evolve together, creating a virus-antibody "arms race." Analysis of samples from an individual designated CH505 has illustrated the interplay between an antibody lineage, CH103, and autologous viruses at various time points. The CH103 antibodies, relatively broad in their neutralization spectrum, interact with the CD4 binding site of gp120, with a contact dominated by CDRH3. We show by analyzing structures of progenitor and intermediate antibodies and by correlating them with measurements of binding to various gp120s that there was a shift in the relative orientation of the light- and heavy-chain variable domains during evolution of the CH103 lineage. We further show that mutations leading to this conformational shift probably occurred in response to insertions in variable loop 5 (V5) of the HIV envelope. The shift displaced the tips of the light chain away from contact with V5, making room for the inserted residues, which had allowed escape from neutralization by the progenitor antibody. These results, which document the selective mechanism underlying this example of a virus-antibody arms race, illustrate the functional significance of affinity maturation by mutation outside the complementarity determining region surface of the antibody molecule.

  8. Effects of alkalinity and salinity at low and high light intensity on hydrogen isotope fractionation of long-chain alkenones produced by Emiliania huxleyi

    Directory of Open Access Journals (Sweden)

    G. M. Weiss

    2017-12-01

    Full Text Available Over the last decade, hydrogen isotopes of long-chain alkenones have been shown to be a promising proxy for reconstructing paleo sea surface salinity due to a strong hydrogen isotope fractionation response to salinity across different environmental conditions. However, to date, the decoupling of the effects of alkalinity and salinity, parameters that co-vary in the surface ocean, on hydrogen isotope fractionation of alkenones has not been assessed. Furthermore, as the alkenone-producing haptophyte, Emiliania huxleyi, is known to grow in large blooms under high light intensities, the effect of salinity on hydrogen isotope fractionation under these high irradiances is important to constrain before using δDC37 to reconstruct paleosalinity. Batch cultures of the marine haptophyte E. huxleyi strain CCMP 1516 were grown to investigate the hydrogen isotope fractionation response to salinity at high light intensity and independently assess the effects of salinity and alkalinity under low-light conditions. Our results suggest that alkalinity does not significantly influence hydrogen isotope fractionation of alkenones, but salinity does have a strong effect. Additionally, no significant difference was observed between the fractionation responses to salinity recorded in alkenones grown under both high- and low-light conditions. Comparison with previous studies suggests that the fractionation response to salinity in culture is similar under different environmental conditions, strengthening the use of hydrogen isotope fractionation as a paleosalinity proxy.

  9. Effects of alkalinity and salinity at low and high light intensity on hydrogen isotope fractionation of long-chain alkenones produced by Emiliania huxleyi

    Science.gov (United States)

    Weiss, Gabriella M.; Pfannerstill, Eva Y.; Schouten, Stefan; Sinninghe Damsté, Jaap S.; van der Meer, Marcel T. J.

    2017-12-01

    Over the last decade, hydrogen isotopes of long-chain alkenones have been shown to be a promising proxy for reconstructing paleo sea surface salinity due to a strong hydrogen isotope fractionation response to salinity across different environmental conditions. However, to date, the decoupling of the effects of alkalinity and salinity, parameters that co-vary in the surface ocean, on hydrogen isotope fractionation of alkenones has not been assessed. Furthermore, as the alkenone-producing haptophyte, Emiliania huxleyi, is known to grow in large blooms under high light intensities, the effect of salinity on hydrogen isotope fractionation under these high irradiances is important to constrain before using δDC37 to reconstruct paleosalinity. Batch cultures of the marine haptophyte E. huxleyi strain CCMP 1516 were grown to investigate the hydrogen isotope fractionation response to salinity at high light intensity and independently assess the effects of salinity and alkalinity under low-light conditions. Our results suggest that alkalinity does not significantly influence hydrogen isotope fractionation of alkenones, but salinity does have a strong effect. Additionally, no significant difference was observed between the fractionation responses to salinity recorded in alkenones grown under both high- and low-light conditions. Comparison with previous studies suggests that the fractionation response to salinity in culture is similar under different environmental conditions, strengthening the use of hydrogen isotope fractionation as a paleosalinity proxy.

  10. A Four-Type Decision-Variable MINLP Model for a Supply Chain Network Design

    Directory of Open Access Journals (Sweden)

    M. M. Monteiro

    2010-01-01

    Full Text Available We propose a mixed integer nonlinear programming model for the design of a one-period planning horizon supply chain with integrated and flexible decisions on location of plants and of warehouses, on levels of production and of inventory, and on transportation models, considering stochastic demand and the ABC classification for finished goods, which is an NP-hard industrial engineering optimization problem. Furthermore, computational implementation of the proposed model is presented through the direct application of the outer approximation algorithm on some randomly generated supply chain data.

  11. Interactions of monochromatic visible light and near-IR radiation with cells: currently discussed mechanisms

    Science.gov (United States)

    Karu, Tiina I.

    1995-05-01

    Biological responses of cells to visible and near IR (laser) radiation occur due to physical and/or chemical changes in photoacceptor molecules, components of respiratory chains (cyt a/a3 in mitochondria, and cyt d in E. coli). As a result of the photoexcitation of electronic states, the following physical and/or chemical changes can occur: alteration of redox properties and acceleration of electron transfer, changes in biochemical activity due to local transient heating of chromophores, one-electron auto-oxidation and O2- production, and photodynamic action and 1O2 production. Different reaction channels can be activated to achieve the photobiological macroeffect. The primary physical and/or chemical changes induced by light in photoacceptor molecules are followed by a cascade of biochemical reactions in the cell that do not need further light activation and occur in the dark (photosignal transduction and amplification chains). These reactions are connected with changes in cellular homeostasis parameters. The crucial step here is thought to be an alteration of the cellular redox state: a shift towards oxidation is associated with stimulation of cellular vitality, and a shift towards reduction is linked to inhibition. Cells with a lower than normal pH, where the redox state is shifted in the reduced direction, are considered to be more sensitive to the stimulative action of light than those with the respective parameters being optimal or near optimal. This circumstance explains the possible variations in observed magnitudes of low-power laser effects. Light action on the redox state of a cell via the respiratory chain also explains the diversity of low-power laser effects. Beside explaining many controversies in the field of low-power laser effects (i.e., the diversity of effects, the variable magnitude or absence of effects in certain studies), the proposed redox-regulation mechanism may be a fundamental explanation of some clinical effects of irradiation, for

  12. Application of monosymmetrical I-beams in light metal frames with variable stiffness

    Directory of Open Access Journals (Sweden)

    I.O. Sklyarov

    2016-05-01

    Full Text Available The article is devoted to effectiveness of using of monosymmetrical I-beams with flexible wall frame structures of variable section, features of their calculation and design. Aim: The aim of research is to confirm the feasibility of I-beams with flexible wall bearing as light metal skeletons for buildings of the universal assignment. Materials and Methods: In order to reduce the metal consumption a frame is conventionally divided into several sections according to bending moment diagrams so that in the more compressed zone section the belt of great area was located, and in the stretched or less intense zone the lesser belt was installed. The resulting sections have smaller area in compare to symmetric profiles. Additional reduce bending moments provided as a result of displacement of elements axes with variable cross section. Results: The calculations and selection of sections of the frame have shown that it can be achieved the reducing of bearing elements weight by 10% compared to the symmetrical profiles of variable stiffness due to using monosymmetrical sections. The effectiveness of the proposed constructive solution is confirmed by compare of the projected weight frame construction with existing analogue. The symmetrical frame profile is 15.3% lighter; the monosymmetrical frame profile is 27% lighter. Conclusions: Analysis of stress-strain state structures shown: first, through asymmetrical profile there is a shifting of the center of gravity section, which leads to a redistribution of internal forces in the frame; secondly, because of the small cross-sectional area of the stretched zones more difficult to ensure the stability of the plane form of bending beams, which leads to the necessity to disconnect areas curtain beams by constraints of smaller steps.

  13. A novel anti-alpha-fetoprotein single-chain variable fragment displays anti-tumor effects in HepG2 cells as a single agent or in combination with paclitaxel.

    Science.gov (United States)

    Ji, Xiaonan; Shen, Yanli; Sun, Hao; Gao, Xiangdong

    2016-08-01

    Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The function of alpha-fetoprotein (AFP) as a regulatory factor in the growth of HCC cells has been well defined. The aim of this study was to investigate the use of a novel AFP-specific single-chain variable fragment that blocked AFP and inhibited HCC cell growth. The results indicated that the anti-AFP single-chain variable fragment (scFv) induced growth inhibition of AFP-expressing HCC cell lines in vitro through induction of G1 cell cycle arrest and apoptosis. The mechanism of apoptosis probably involved with blocking AFP internalization and regulation of the PTEN/PI3K/Akt signaling network. Moreover, the anti-AFP-scFv also effectively sensitized the HepG2 cells to paclitaxel (PTX) at a lower concentration. The combination effect of PTX and anti-AFP-scFv displayed a synergistic effect on HepG2 cells both in vitro and in vivo. Our results demonstrated that targeting AFP by specific antibodies has potential immunotherapeutic efficacy in human HCC.

  14. Philips Electronics synchronizes its supply chain to end the bullwhip effect

    NARCIS (Netherlands)

    Kok, de A.G.; Janssen, F.B.S.L.P.; van Doremalen, J.B.M.; Wachem, van E.; Clerkx, M.J.R.; Peeters, W.

    2005-01-01

    Demand variability increases as one moves up a supply chain. The demand for finished products is less variable than for subassemblies, which is less variable than for individual components. This phenomenon is known as the bullwhip or Forrester effect. It increases inventory unnecessarily and makes

  15. Cardiac-Specific Gene Expression Facilitated by an Enhanced Myosin Light Chain Promoter

    Directory of Open Access Journals (Sweden)

    Wolfgang Boecker

    2004-04-01

    Full Text Available Background: Adenoviral gene transfer has been shown to be effective in cardiac myocytes in vitro and in vivo. A major limitation of myocardial gene therapy is the extracardiac transgene expression. Methods: To minimize extracardiac gene expression, we have constructed a tissue-specific promoter for cardiac gene transfer, namely, the 250-bp fragment of the myosin light chain-2v (MLC-2v gene, which is known to be expressed in a tissue-specific manner in ventricular myocardium followed by a luciferase (luc reporter gene (Ad.4 × MLC250.Luc. Rat cardiomyocytes, liver and kidney cells were infected with Ad.4 × MLC.Luc or control vectors. For in vivo testing, Ad.4 × MLC250.Luc was injected into the myocardium or in the liver of rats. Kinetics of promoter activity were monitored over 8 days using a cooled CCD camera. Results: In vitro: By infecting hepatic versus cardiomyocyte cells, we found that the promoter specificity ratio (luc activity in cardiomyocytes per liver cells was 20.4 versus 0.9 (Ad.4 × MLC250.Luc vs. Ad.CMV. In vivo: Ad.4 × MLC250.Luc significantly reduced luc activity in liver (38.4-fold, lung (16.1-fold, and kidney (21.8-fold versus Ad.CMV (p = .01; whereas activity in the heart was only 3.8-fold decreased. The gene expression rate of cardiomyocytes versus hepatocytes was 7:1 (Ad.4 × MLC.Luc versus 1:1.4 (Ad.CMV.Luc. Discussion: This new vector may be useful to validate therapeutic approaches in animal disease models and offers the perspective for selective expression of therapeutic genes in the diseased heart.

  16. Effective use of product quality information in food supply chain logistics

    NARCIS (Netherlands)

    Rijpkema, W.A.

    2014-01-01

    Food supply chains have inherent characteristics, such as variability in product quality and quality decay, which put specific demands on logistics decision making. Furthermore, food supply chain organization and control has changed significantly in the past decades by factors such as scale

  17. The TUS space fluorescence detector for study of UHECR and other phenomena of variable fluorescence light in the atmosphere

    Science.gov (United States)

    Abrashkin, V.; Alexandrov, V.; Arakcheev, Y.; Bitkin, E.; Cordero, A.; Eremin, S.; Finger, M.; Garipov, G.; Grebenyuk, V.; Kalmykov, N.; Khrenov, B.; Koval, V.; Martinez, O.; Matyushkin, A.; Moreno, E.; Naumov, D.; Olshevsky, A.; Panasyuk, M.; Park, I.; Robledo, C.; Rubinstein, I.; Sharakin, S.; Silaev, A.; Tkatchev, L.; Tulupov, V.; Tyukaev, R.; Sabirov, B.; Salazar, H.; Saprykin, O.; Syromyatnikov, V.; Urmantsev, F.; Villasenor, L.; Yashin, I.; Zaikin, N.; Zepeda, A.

    The Tracking Ultraviolet Set Up (TUS) instrument has been designed to observe from space the fluorescence light in the atmosphere when Extensive Air Shower (EAS) or other phenomena such as meteors or dust grains traverse it. The TUS design concepts will allow us to construct the next generation of fluorescence detectors with increasing light collection power and higher resolution. The KLYPVE instrument with collection power 5 times larger of the TUS will be the next space detector. Light collection is obtained with the help of segmented “low frequency Fresnel type” mirrors. Photo receiver retina in the focal consists of modules of PM tubes. For stable performance in conditions of variable light noise and variable temperature the tube type with a multi-alcali cathode was chosen. Voltage supplies for PMT in one module were designed for keeping the performance of photo receiver retina uniform when the tube gain change. From every tube the signal amplitude is recorded in time bins of 400 ns. The digital data are kept and analyzed in the module FPGA connected to the central FPGA controlling all data. The RAM memory is large, capable to record events with different duration of the light signal (up to several seconds). The preliminary event data are analyzed in the triggering system of the central FPGA. The trigger criteria have several options for events of different origin (different pixel signal duration). The trigger integration time is controlled from the space mission center. The performances of the detector were simulated and zenith angle dependent trigger efficiencies were calculated. The TUS detector will be efficient in recording “horizontal” EAS (zenith angles more than 60°), developed to their maximum above the cloud cover. The EAS Cherenkov light, back scattered from the cloud cover, will be recorded and will improve data on the EAS direction and position of maximum. For better accuracy in physical parameters of the events and for the experimental

  18. Variation in N-linked carbohydrate chains in different batches of two chimeric monoclonal IgG1 antibodies produced by different murine SP2/0 transfectoma cell subclones.

    Science.gov (United States)

    Bergwerff, A A; Stroop, C J; Murray, B; Holtorf, A P; Pluschke, G; Van Oostrum, J; Kamerling, J P; Vliegenthart, J F

    1995-06-01

    Two chimeric human/murine monoclonal antibodies were constructed by substitution of the murine constant regions with human gamma 1 and kappa constant regions for heavy and light chains, respectively. The chimeric human/murine molecules are anti-idiotypic antibodies, meaning that they were directed against the antigen binding site in the variable region of another antibody. Antibody batches were produced under identical production conditions, using two selected SP2/0 myeloma cell subclones, which produce chimeric antibodies with different variable regions, but identical constant regions. Several samples were collected during the production of the antibodies in hollow-fibre reactors. The heavy chain, but not the light chain, of the two different chimeric IgG1 antibodies is glycosylated. Structural analysis of the enzymically released N-linked carbohydrate chains by 1H-NMR spectroscopy, as well as by chromatographic profiling, demonstrated that the collection of N-glycans comprises a small amount of monoantennary, and for the greater part diantennary structures. The N-glycans are completely (alpha 1-->6)-fucosylated at the innermost GlcNAc residue. The antennae of the neutral diantennary N-glycans are built up from GlcNAc beta 1-->2, Gal beta 1-->4GlcNAc beta 1-->2 or Gal alpha 1-->3G alpha 1 beta 1-->4GlcNAc beta 1-->2 elements, whereas the antennae of the neutral monoantennary carbohydrate chains have only (beta 1-->2)-linked GlcNAc residues. Galactosylation of the GlcNAc beta 1-->2Man alpha 1-->6 branch occurs four times more frequently than that of the GlcNAc beta 1-->2Man alpha 1-->3 branch, independently of the production batch. A small amount of the diantennary N-glycans are mono- or disialylated, carrying N-acetylneuraminic acid (Neu5Ac) or N-glycolylneuraminic acid (Neu5Gc), exclusively (alpha 2-->6)-linked to beta Gal. Analysis of the different production batches demonstrates that the structures of the N-linked carbohydrate chains are identical in the two

  19. The Level of Psychological Burnout at the Teachers of Students with Autism Disorders in Light of a Number of Variables in Al-Riyadh Area

    Science.gov (United States)

    Atiyat, Omar Khalil

    2017-01-01

    This study aimed at measuring the level of the psychological burnout in the teachers of students that have autism symptoms in Al-Riyadh area--kingdom of Saudi Arabia. In light of variables. These variables are the gender, the teaching place, the academic qualification of the teachers, the experience of the teachers, the age of the teachers, and…

  20. Photoinduced Circular Anisotropy in Side-Chain Azobenzene Polyesters

    DEFF Research Database (Denmark)

    Nikolova, L.; Todorov, T.; Ivanov, M.

    1997-01-01

    We report for the first time the inducing of large circular anisotropy in previously unoriented films of side-chain azobenzene polyesters on illumination with circularly polarized light at a wavelength of 488 nm. The circular dichroism and optical activity are measured simultaneously in real time...

  1. Flexibility evaluation of multiechelon supply chains.

    Directory of Open Access Journals (Sweden)

    João Flávio de Freitas Almeida

    Full Text Available Multiechelon supply chains are complex logistics systems that require flexibility and coordination at a tactical level to cope with environmental uncertainties in an efficient and effective manner. To cope with these challenges, mathematical programming models are developed to evaluate supply chain flexibility. However, under uncertainty, supply chain models become complex and the scope of flexibility analysis is generally reduced. This paper presents a unified approach that can evaluate the flexibility of a four-echelon supply chain via a robust stochastic programming model. The model simultaneously considers the plans of multiple business divisions such as marketing, logistics, manufacturing, and procurement, whose goals are often conflicting. A numerical example with deterministic parameters is presented to introduce the analysis, and then, the model stochastic parameters are considered to evaluate flexibility. The results of the analysis on supply, manufacturing, and distribution flexibility are presented. Tradeoff analysis of demand variability and service levels is also carried out. The proposed approach facilitates the adoption of different management styles, thus improving supply chain resilience. The model can be extended to contexts pertaining to supply chain disruptions; for example, the model can be used to explore operation strategies when subtle events disrupt supply, manufacturing, or distribution.

  2. Conceptual design of a pressure tube light water reactor with variable moderator control

    International Nuclear Information System (INIS)

    Rachamin, R.; Fridman, E.; Galperin, A.

    2012-01-01

    This paper presents the development of innovative pressure tube light water reactor with variable moderator control. The core layout is derived from a CANDU line of reactors in general, and advanced ACR-1000 design in particular. It should be stressed however, that while some of the ACR-1000 mechanical design features are adopted, the core design basics of the reactor proposed here are completely different. First, the inter fuel channels spacing, surrounded by the calandria tank, contains a low pressure gas instead of heavy water moderator. Second, the fuel channel design features an additional/external tube (designated as moderator tube) connected to a separate moderator management system. The moderator management system is design to vary the moderator tube content from 'dry' (gas) to 'flooded' (light water filled). The dynamic variation of the moderator is a unique and very important feature of the proposed design. The moderator variation allows an implementation of the 'breed and burn' mode of operation. The 'breed and burn' mode of operation is implemented by keeping the moderator tube empty ('dry' filled with gas) during the breed part of the fuel depletion and subsequently introducing the moderator by 'flooding' the moderator tube for the 'burn' part. This paper assesses the conceptual feasibility of the proposed concept from a neutronics point of view. (authors)

  3. Properties of Confined Star-Branched and Linear Chains. A Monte Carlo Simulation Study

    International Nuclear Information System (INIS)

    Romiszowski, P.; Sikorski, A.

    2004-01-01

    A model of linear and star-branched polymer chains confined between two parallel and impenetrable surfaces was built. The polymer chains were restricted to a simple cubic lattice. Two macromolecular architectures of the chain: linear and star branched (consisted of f = 3 branches of equal length) were studied. The excluded volume was the only potential introduced into the model (the athermal system). Monte Carlo simulations were carried out using a sampling algorithm based on chain's local changes of conformation. The simulations were carried out at different confinement conditions: from light to high chain's compression. The scaling of chain's size with the chain length was studied and discussed. The influence of the confinement and the macromolecular architecture on the shape of a chain was studied. The differences in the shape of linear and star-branched chains were pointed out. (author)

  4. Effective use of product quality information in food supply chain logistics

    OpenAIRE

    Rijpkema, W.A.

    2014-01-01

    Food supply chains have inherent characteristics, such as variability in product quality and quality decay, which put specific demands on logistics decision making. Furthermore, food supply chain organization and control has changed significantly in the past decades by factors such as scale intensification and globalization. In practice, these characteristics and developments frequently lead to supply chain problems, such as high levels of product waste, product quality problems, and high lo...

  5. Discrete-Choice Modeling Of Non-Working Women’s Trip-Chaining Activity Based

    Science.gov (United States)

    Hayati, Amelia; Pradono; Purboyo, Heru; Maryati, Sri

    2018-05-01

    Start The urban developments of technology and economics are now changing the lifestyles of the urban societies. It is also changing their travel demand to meet their movement needs. Nowadays, urban women, especially in Bandung, West Java, have a high demand for their daily travel and tend to increase. They have the ease of accessibility to personal modes of transportation and freedom to go anywhere to meet their personal and family needs. This also happens to non-working women or as housewives in the city of Bandung. More than 50% of women’s mobility is outside the home, in the term of trip-chaining, from leaving to returning home in one day. It is based on their complex activities in order to meet the needs of family and home care. While less than 60% of male’s mobility is outdoors, it is a simple trip-chaining or only has a single trip. The trip-chaining has significant differences between non-working women and working-men. This illustrates the pattern of Mom and Dad’s mobility in a family with an activity-based approach for the same purpose, i.e. family welfare. This study explains how complex the trip-chaining of non-working urban women and as housewives, with an activity-based approach done outdoors in a week. Socio-economic and household demographic variables serve as the basis for measuring the independent variables affecting family welfare, as well as the variables of type, time and duration of activities performed by unemployed housewives. This study aims to examine the interrelationships between activity variables, especially the time of activity and travel, and socio-economic of household variables that can generate the complexity of women’s daily travel. Discrete Choice Modeling developed by Ben-Akiva, Chandra Bhat, etc., is used in this study to illustrate the relationship between activity and socio-economic demographic variables based on primary survey data in Bandung, West Java for 466 unemployed housewives. The results of the regression, by

  6. A continuous-variable quantum memory for light

    DEFF Research Database (Denmark)

    Dantan, Aurélien; Cviklinski, J.; Ortalo, J.

    We study here a different scheme involving a large ensemble of Lambda-type atoms, a control field, and the field to be stored and show how to transfer with a nearly 100% efficiency a quantum state of light (squeezed vacuum) into the ground state coherence of a spin-polarized atomic cloud. We find...

  7. Modelling antibody side chain conformations using heuristic database search.

    Science.gov (United States)

    Ritchie, D W; Kemp, G J

    1997-01-01

    We have developed a knowledge-based system which models the side chain conformations of residues in the variable domains of antibody Fv fragments. The system is written in Prolog and uses an object-oriented database of aligned antibody structures in conjunction with a side chain rotamer library. The antibody database provides 3-dimensional clusters of side chain conformations which can be copied en masse into the model structure. The object-oriented database architecture facilitates a navigational style of database access, necessary to assemble side chains clusters. Around 60% of the model is built using side chain clusters and this eliminates much of the combinatorial complexity associated with many other side chain placement algorithms. Construction and placement of side chain clusters is guided by a heuristic cost function based on a simple model of side chain packing interactions. Even with a simple model, we find that a large proportion of side chain conformations are modelled accurately. We expect our approach could be used with other homologous protein families, in addition to antibodies, both to improve the quality of model structures and to give a "smart start" to the side chain placement problem.

  8. Dissect Kif5b in nuclear positioning during myogenesis: The light chain binding domain and the autoinhibitory peptide are both indispensable

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zai, E-mail: wangzai81@hotmail.com [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Institute of Clinical Medical Sciences, China–Japan Friendship Hospital, Beijing (China); Xue, Wenqian; Li, Xiuling; Lin, Raozhou [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Cui, Ju [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong); Beijing Institute of Geriatrics, Beijing Hospital, Ministry of Health (China); Huang, Jian-Dong, E-mail: jdhuang@hku.hk [Department of Biochemistry, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam (Hong Kong)

    2013-03-08

    Highlights: ► Kif5b localizes at myonuclear membrane and is responsible for nuclear dispersion. ► Kif5b stalk/tail domain contains signal for nuclear membrane targeting. ► Kif5b stalk/tail domain directly binds to a nesprin 4 in vitro. ► KLC binding domain and autoinhibitory peptide are both functionally indispensable. -- Abstract: The microtubule motor kinesin-1 is responsible for the nuclear positioning during myogenesis. Here we show that the coiled-coil stalk/tail domain containing the kinesin light chain (KLC) binding sites targets to the perinuclear region like endogenous Kif5b, while the globular tail domain cannot. To investigate which fragments of kinesin heavy chain (Kif5b) is responsible for the myonuclear positioning, we transfect Kif5b expression constructs into Kif5b deficient myoblasts and test their ability to rescue the myonuclear phenotype. We find that the KLC binding domain and the autoinhibitory peptide in the globular tail region are both indispensable for the nuclear membrane localization of Kif5b and the kinesin-1-mediated myonuclear positioning. These results suggest that while the KLC binding domain may directly targets Kif5b to the myonuclear membrane, the autoinhibitory peptide may play an indirect role in regulating the kinesin-1-mediated myonuclear positioning.

  9. Immunoglobulin free light chains are increased in hypersensitivity pneumonitis and idiopathic pulmonary fibrosis.

    Directory of Open Access Journals (Sweden)

    Tom Groot Kormelink

    Full Text Available BACKGROUND: Idiopathic pulmonary fibrosis (IPF, a devastating lung disorder of unknown aetiology, and chronic hypersensitivity pneumonitis (HP, a disease provoked by an immunopathologic reaction to inhaled antigens, are two common interstitial lung diseases with uncertain pathogenic mechanisms. Previously, we have shown in other upper and lower airway diseases that immunoglobulin free light chains (FLCs are increased and may be involved in initiating a local inflammation. In this study we explored if such a mechanism may also apply to HP and IPF. METHODS: In this study we examined the presence of FLC in serum and BAL fluid from 21 IPF and 22 HP patients and controls. IgG, IgE and tryptase concentrations were measured in BAL fluid only. The presence of FLCs, plasma cells, B cells and mast cells in lung tissue of 3 HP and 3 IPF patients and 1 control was analyzed using immunohistochemistry. RESULTS: FLC concentrations in serum and BAL fluid were increased in IPF and HP patients as compared to control subjects. IgG concentrations were only increased in HP patients, whereas IgE concentrations were comparable to controls in both patient groups. FLC-positive cells, B cells, plasma cells, and large numbers of activated mast cells were all detected in the lungs of HP and IPF patients, not in control lung. CONCLUSION: These results show that FLC concentrations are increased in serum and BAL fluid of IPF and HP patients and that FLCs are present within affected lung tissue. This suggests that FLCs may be involved in mediating pathology in both diseases.

  10. Design and Generation of Humanized Single-chain Fv Derived from Mouse Hybridoma for Potential Targeting Application.

    Science.gov (United States)

    Khantasup, Kannika; Chantima, Warangkana; Sangma, Chak; Poomputsa, Kanokwan; Dharakul, Tararaj

    2015-12-01

    Single-chain variable antibody fragments (scFvs) are attractive candidates for targeted immunotherapy in several human diseases. In this study, a concise humanization strategy combined with an optimized production method for humanizing scFvs was successfully employed. Two antibody clones, one directed against the hemagglutinin of H5N1 influenza virus, the other against EpCAM, a cancer biomarker, were used to demonstrate the validity of the method. Heavy chain (VH) and light chain (VL) variable regions of immunoglobulin genes from mouse hybridoma cells were sequenced and subjected to the construction of mouse scFv 3-D structure. Based on in silico modeling, the humanized version of the scFv was designed via complementarity-determining region (CDR) grafting with the retention of mouse framework region (FR) residues identified by primary sequence analysis. Root-mean-square deviation (RMSD) value between mouse and humanized scFv structures was calculated to evaluate the preservation of CDR conformation. Mouse and humanized scFv genes were then constructed and expressed in Escherichia coli. Using this method, we successfully generated humanized scFvs that retained the targeting activity of their respective mouse scFv counterparts. In addition, the humanized scFvs were engineered with a C-terminal cysteine residue (hscFv-C) for site-directed conjugation for use in future targeting applications. The hscFv-C expression was extensively optimized to improve protein production yield. The protocol yielded a 20-fold increase in production of hscFv-Cs in E. coli periplasm. The strategy described in this study may be applicable in the humanization of other antibodies derived from mouse hybridoma.

  11. Supply chain performance: the role of regional markets

    Directory of Open Access Journals (Sweden)

    Ali Ghasemi

    2015-05-01

    Full Text Available This paper investigates the role of exports in the regional markets on the performance of supply chain. The study first determines critical variables affecting exports for entering into the regional markets and then measures the effects of these variables on the effectiveness of supply chain performance. The study uses two questionnaires, one for measuring the effects of various factors on export development and the other for measuring supply chain performance in Likert scale. Cronbach alpha for the mentioned questionnaires were calculated as 0.84 and 0.78, respectively. The population of the survey includes all small and medium enterprises active in city of Tehran, Iran and the study selects a sample of 250 people as a sample size. Using factor analysis, the study has determined seven factors including product development, government support, strategic orientation, customer satisfaction, competitive pressures, organizational capability and distribution strategies for entry into regional markets. In addition, the implementation of structural equation modeling has disclosed that product development and distribution strategies maintained the highest impact on export activities.

  12. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species.

    Directory of Open Access Journals (Sweden)

    Xifeng Wang

    Full Text Available Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλn. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates.

  13. A Comprehensive Analysis of the Phylogeny, Genomic Organization and Expression of Immunoglobulin Light Chain Genes in Alligator sinensis, an Endangered Reptile Species

    Science.gov (United States)

    Lu, Yan; Zhang, Chenglin; Wu, Xiaobing; Han, Haitang; Zhao, Yaofeng; Ren, Liming

    2016-01-01

    Crocodilians are evolutionarily distinct reptiles that are distantly related to lizards and are thought to be the closest relatives of birds. Compared with birds and mammals, few studies have investigated the Ig light chain of crocodilians. Here, employing an Alligator sinensis genomic bacterial artificial chromosome (BAC) library and available genome data, we characterized the genomic organization of the Alligator sinensis IgL gene loci. The Alligator sinensis has two IgL isotypes, λ and κ, the same as Anolis carolinensis. The Igλ locus contains 6 Cλ genes, each preceded by a Jλ gene, and 86 potentially functional Vλ genes upstream of (Jλ-Cλ)n. The Igκ locus contains a single Cκ gene, 6 Jκs and 62 functional Vκs. All VL genes are classified into a total of 31 families: 19 Vλ families and 12 Vκ families. Based on an analysis of the chromosomal location of the light chain genes among mammals, birds, lizards and frogs, the data further confirm that there are two IgL isotypes in the Alligator sinensis: Igλ and Igκ. By analyzing the cloned Igλ/κ cDNA, we identified a biased usage pattern of V families in the expressed Vλ and Vκ. An analysis of the junctions of the recombined VJ revealed the presence of N and P nucleotides in both expressed λ and κ sequences. Phylogenetic analysis of the V genes revealed V families shared by mammals, birds, reptiles and Xenopus, suggesting that these conserved V families are orthologous and have been retained during the evolution of IgL. Our data suggest that the Alligator sinensis IgL gene repertoire is highly diverse and complex and provide insight into immunoglobulin gene evolution in vertebrates. PMID:26901135

  14. Assessing responsiveness of a volatile and seasonal supply chain

    DEFF Research Database (Denmark)

    Wong, Chee Yew; Arlbjørn, Jan Stentoft; Hvolby, Hans Henrik

    2006-01-01

    ‘‘market responsive’’ and ‘‘physically efficient’’ supply chains constitutes the backbone of this assessment. Four risk-influencing determinants—forecast uncertainty, demand variability, contribution margin, and time window of delivery are found suitable to assess the responsiveness of the toy supply chain......This paper describes a structural approach to assess the responsiveness of a volatile and seasonal supply chain. It is based on a case study in an international toy company. Fisher’s (Harvard Bus. Rev. 75(2) (1997) 105–117) Model of ‘‘innovative’’ and ‘‘functional’’ products and the corresponding...... with volatility, and to design for a responsive supply chain. These findings have also enabled the extension of Fisher’s Model to volatile supply chains. This new product differentiation model adds a physically responsive supply chain for ‘‘intermediate’’ products into the Fisher’s Model....

  15. Modulation of neutrophil superoxide generation by inhibitors of protein kinase C, calmodulin, diacylglycerol and myosin light chain kinases, and peptidyl prolyl cis-trans isomerase.

    Science.gov (United States)

    Bergstrand, H; Eriksson, T; Hallberg, A; Johansson, B; Karabelas, K; Michelsen, P; Nybom, A

    1992-12-01

    To assess the role of protein kinase C (PKC) in the respiratory burst of adherent human polymorphonuclear leukocytes (PMNL), reduction of ferricytochrome C by cells triggered with a phorbol ester (PMA), ionophore A23187, serum-treated zymosan (STZ) or three lipid derivatives, 3-decanoyl-sn-glycerol (G-3-OCOC9), (R,R)-1,4-diethyl-2-O-decyl-L-tartrate (Tt-2-OC10) and 3-decyloxy-5-hydroxymethylphenol (DHP) was examined in a microtiter plate procedure in the presence of inhibitors of PKC and, for comparison, inhibitors of calmodulin, diacylglycerol and myosin light chain kinases and the peptidyl-prolyl cis-trans isomerase activity of fujiphilin. 1) Of the protein kinase inhibitors examined, Ro 31-7549 and staurosporine reduced responses to all stimuli except possibly STZ; in contrast, K252a and the myosin light chain kinase inhibitors ML-7 and ML-9 blocked responses to A23187 and STZ better than those triggered by PMA. H-7 reduced responses to A23187, DHP and G-3-OCOC9, and calphostin, palmitoyl carnitine, sphingosine and the multifunctional drugs TMB-8 and W-7 reduced A23187; they also, when examined, reduced decane derivative-induced O2- production more effectively than PMA- and STZ-triggered responses. Polymyxin B, 4 alpha-PMA and retinal displayed no inhibitory capacity. 2) Of the selective calmodulin antagonists, CGS 9343B, Ro 22-4839 and calmidazolium did not inhibit the oxidative response irrespective of the stimulus used, whereas metofenazate reduced those evoked by A23187, DHP, G-3-OCOC9 and STZ.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Continuous Variable Quantum Communication and Computation

    DEFF Research Database (Denmark)

    Andersen, Ulrik Lund; Dong, Ruifang; Jezek, Miroslav

    2011-01-01

    We use squeezed states of light to implement a robust continuous variable quantum key distribution scheme and an optical Hadamard gate based on coherent state qubits.......We use squeezed states of light to implement a robust continuous variable quantum key distribution scheme and an optical Hadamard gate based on coherent state qubits....

  17. N-terminus of Cardiac Myosin Essential Light Chain Modulates Myosin Step-Size

    Science.gov (United States)

    Wang, Yihua; Ajtai, Katalin; Kazmierczak, Katarzyna; Szczesna-Cordary, Danuta; Burghardt, Thomas P.

    2016-01-01

    Muscle myosin cyclically hydrolyzes ATP to translate actin. Ventricular cardiac myosin (βmys) moves actin with three distinct unitary step-sizes resulting from its lever-arm rotation and with step-frequencies that are modulated in a myosin regulation mechanism. The lever-arm associated essential light chain (vELC) binds actin by its 43 residue N-terminal extension. Unitary steps were proposed to involve the vELC N-terminal extension with the 8 nm step engaging the vELC/actin bond facilitating an extra ~19 degrees of lever-arm rotation while the predominant 5 nm step forgoes vELC/actin binding. A minor 3 nm step is the unlikely conversion of the completed 5 to the 8 nm step. This hypothesis was tested using a 17 residue N-terminal truncated vELC in porcine βmys (Δ17βmys) and a 43 residue N-terminal truncated human vELC expressed in transgenic mouse heart (Δ43αmys). Step-size and step-frequency were measured using the Qdot motility assay. Both Δ17βmys and Δ43αmys had significantly increased 5 nm step-frequency and coincident loss in the 8 nm step-frequency compared to native proteins suggesting the vELC/actin interaction drives step-size preference. Step-size and step-frequency probability densities depend on the relative fraction of truncated vELC and relate linearly to pure myosin species concentrations in a mixture containing native vELC homodimer, two truncated vELCs in the modified homodimer, and one native and one truncated vELC in the heterodimer. Step-size and step-frequency, measured for native homodimer and at two or more known relative fractions of truncated vELC, are surmised for each pure species by using a new analytical method. PMID:26671638

  18. Nuclear Physics on the Light Front

    OpenAIRE

    Miller, Gerald A.

    1999-01-01

    High energy scattering experiments involving nuclei are typically analyzed in terms of light front variables. The desire to provide realistic, relativistic wave functions expressed in terms of these variables led me to try to use light front dynamics to compute nuclear wave functions. The progress is summarized here.

  19. THE CHANDRA VARIABLE GUIDE STAR CATALOG

    International Nuclear Information System (INIS)

    Nichols, Joy S.; Lauer, Jennifer L.; Morgan, Douglas L.; Sundheim, Beth A.; Henden, Arne A.; Huenemoerder, David P.; Martin, Eric

    2010-01-01

    Variable stars have been identified among the optical-wavelength light curves of guide stars used for pointing control of the Chandra X-ray Observatory. We present a catalog of these variable stars along with their light curves and ancillary data. Variability was detected to a lower limit of 0.02 mag amplitude in the 4000-10000 A range using the photometrically stable Aspect Camera on board the Chandra spacecraft. The Chandra Variable Guide Star Catalog (VGUIDE) contains 827 stars, of which 586 are classified as definitely variable and 241 are identified as possibly variable. Of the 586 definite variable stars, we believe 319 are new variable star identifications. Types of variables in the catalog include eclipsing binaries, pulsating stars, and rotating stars. The variability was detected during the course of normal verification of each Chandra pointing and results from analysis of over 75,000 guide star light curves from the Chandra mission. The VGUIDE catalog represents data from only about 9 years of the Chandra mission. Future releases of VGUIDE will include newly identified variable guide stars as the mission proceeds. An important advantage of the use of space data to identify and analyze variable stars is the relatively long observations that are available. The Chandra orbit allows for observations up to 2 days in length. Also, guide stars were often used multiple times for Chandra observations, so many of the stars in the VGUIDE catalog have multiple light curves available from various times in the mission. The catalog is presented as both online data associated with this paper and as a public Web interface. Light curves with data at the instrumental time resolution of about 2 s, overplotted with the data binned at 1 ks, can be viewed on the public Web interface and downloaded for further analysis. VGUIDE is a unique project using data collected during the mission that would otherwise be ignored. The stars available for use as Chandra guide stars are

  20. The origin of the infrared light of cataclysmic variable stars

    International Nuclear Information System (INIS)

    Berriman, G.; Szkody, P.; Capps, R.W.

    1985-01-01

    This paper presents a model-independent overview of the origin of the near infrared (1-2 μm) light of a sample of 28 cataclysmic binary stars, largely dwarf novae in quiescence. The infrared light comes from the red dwarf that supplies matter to the white dwarf companion and the accretion disc around the white dwarf. The complex nature of the disc prevents near-infrared photometry from being a good probe of the red dwarfs, even in those systems where they are seen in the visual. All that can be found reliably is an upper limit to the proportion light that the red dwarfs supply, and consequently lower limits to the distances to the systems. The infrared light of the discs comes from opaque material and from the optically thin gas that gives rise to the visual and UV emission lines. (author)

  1. PENGARUH MEDIASI KEPERCAYAAN PADA HUBUNGAN ANTARA KOLABORASI SUPPLY CHAIN DAN KINERJA OPERASI

    Directory of Open Access Journals (Sweden)

    Amak M. Yaqoub

    2012-01-01

    Full Text Available This study aims to investigate the mediating role of interorganizational trust on the relationship between supply chain collaboration and operation performance. Supply chain collaboration measured using second order variables; information sharing, incentive alignment, and decision synchronization. Hypotheses testing using SmartPLS confirm positive relationship between supply chain collaboration and interorganizational trust as well as interorganizational trust and operations performance. The direct relationship between supply chain collaboration and operation performance was not significant. These support the mediating role of interorganizational trust.

  2. Low-Frequency Temporal Variability in Mira and Semiregular Variables

    Science.gov (United States)

    Templeton, Matthew R.; Karovska, M.; Waagen, E. O.

    2012-01-01

    We investigate low-frequency variability in a large sample of Mira and semiregular variables with long-term visual light curves from the AAVSO International Database. Our aim is to determine whether we can detect and measure long-timescale variable phenomena in these stars, for example photometric variations that might be associated with supergranular convection. We analyzed the long-term light curves of 522 variable stars of the Mira and SRa, b, c, and d classes. We calculated their low-frequency time-series spectra to characterize rednoise with the power density spectrum index, and then correlate this index with other observable characteristics such as spectral type and primary pulsation period. In our initial analysis of the sample, we see that the semiregular variables have a much broader range of spectral index than the Mira types, with the SRb subtype having the broadest range. Among Mira variables we see that the M- and S-type Miras have similarly wide ranges of index, while the C-types have the narrowest with generally shallower slopes. There is also a trend of steeper slope with larger amplitude, but at a given amplitude, a wide range of slopes are seen. The ultimate goal of the project is to identify stars with strong intrinsic red noise components as possible targets for resolved surface imaging with interferometry.

  3. Effects of breathing patterns and light exercise on linear and nonlinear heart rate variability.

    Science.gov (United States)

    Weippert, Matthias; Behrens, Kristin; Rieger, Annika; Kumar, Mohit; Behrens, Martin

    2015-08-01

    Despite their use in cardiac risk stratification, the physiological meaning of nonlinear heart rate variability (HRV) measures is not well understood. The aim of this study was to elucidate effects of breathing frequency, tidal volume, and light exercise on nonlinear HRV and to determine associations with traditional HRV indices. R-R intervals, blood pressure, minute ventilation, breathing frequency, and respiratory gas concentrations were measured in 24 healthy male volunteers during 7 conditions: voluntary breathing at rest, and metronome guided breathing (0.1, 0.2 and 0.4 Hz) during rest, and cycling, respectively. The effect of physical load was significant for heart rate (HR; p < 0.001) and traditional HRV indices SDNN, RMSSD, lnLFP, and lnHFP (p < 0.01 for all). It approached significance for sample entropy (SampEn) and correlation dimension (D2) (p < 0.1 for both), while HRV detrended fluctuation analysis (DFA) measures DFAα1 and DFAα2 were not affected by load condition. Breathing did not affect HR but affected all traditional HRV measures. D2 was not affected by breathing; DFAα1 was moderately affected by breathing; and DFAα2, approximate entropy (ApEn), and SampEn were strongly affected by breathing. DFAα1 was strongly increased, whereas DFAα2, ApEn, and SampEn were decreased by slow breathing. No interaction effect of load and breathing pattern was evident. Correlations to traditional HRV indices were modest (r from -0.14 to -0.67, p < 0.05 to <0.01). In conclusion, while light exercise does not significantly affect short-time HRV nonlinear indices, respiratory activity has to be considered as a potential contributor at rest and during light dynamic exercise.

  4. Effects of light intensity on components and topographical structures of extracellular polysaccharides from the cyanobacteria Nostoc sp.

    Science.gov (United States)

    Ge, Hongmei; Xia, Ling; Zhou, Xuping; Zhang, Delu; Hu, Chunxiang

    2014-02-01

    A study on the effects of light intensity (40 and 80 μE/m(2)/sec) on the components and topographical structures of extracellular polysaccharides (EPS) was carried out in cyanobacteria Nostoc sp.. EPS yield increased with light intensity. However, light intensity did not significantly affect the EPS fractions and monosaccharide composition. Higher light intensity generally resulted in higher protein content of EPS in similar fractions. The topographical structure of EPS, investigated by atomic force microscopy, appeared as spherical lumps, chains and networks. The long chains were observed at higher light intensity. Thus, light intensity affected the yield and nature of EPS.

  5. Significant differences in physicochemical properties of human immunoglobulin kappa and lambda CDR3 regions

    Directory of Open Access Journals (Sweden)

    Catherine L Townsend

    2016-09-01

    Full Text Available Antibody variable regions are composed of a heavy and a light chain and in humans there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain CDR-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 - light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains, and probed the Protein Data Bank (PDB to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda and heavy chain gene rearrangements are correlated within donors, but can differ between donors. This indicates that TdT may work with differing efficiencies between different people, but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  6. Significant Differences in Physicochemical Properties of Human Immunoglobulin Kappa and Lambda CDR3 Regions.

    Science.gov (United States)

    Townsend, Catherine L; Laffy, Julie M J; Wu, Yu-Chang Bryan; Silva O'Hare, Joselli; Martin, Victoria; Kipling, David; Fraternali, Franca; Dunn-Walters, Deborah K

    2016-01-01

    Antibody variable regions are composed of a heavy and a light chain, and in humans, there are two light chain isotypes: kappa and lambda. Despite their importance in receptor editing, the light chain is often overlooked in the antibody literature, with the focus being on the heavy chain complementarity-determining region (CDR)-H3 region. In this paper, we set out to investigate the physicochemical and structural differences between human kappa and lambda light chain CDR regions. We constructed a dataset containing over 29,000 light chain variable region sequences from IgM-transcribing, newly formed B cells isolated from human bone marrow and peripheral blood. We also used a published human naïve dataset to investigate the CDR-H3 properties of heavy chains paired with kappa and lambda light chains and probed the Protein Data Bank to investigate the structural differences between kappa and lambda antibody CDR regions. We found that kappa and lambda light chains have very different CDR physicochemical and structural properties, whereas the heavy chains with which they are paired do not differ significantly. We also observed that the mean CDR3 N nucleotide addition in the kappa, lambda, and heavy chain gene rearrangements are correlated within donors but can differ between donors. This indicates that terminal deoxynucleotidyl transferase may work with differing efficiencies between different people but the same efficiency in the different classes of immunoglobulin chain within one person. We have observed large differences in the physicochemical and structural properties of kappa and lambda light chain CDR regions. This may reflect different roles in the humoral immune response.

  7. Optical bistability controlling light with light

    CERN Document Server

    Gibbs, Hyatt

    1985-01-01

    Optical Bistability: Controlling Light with Light focuses on optical bistability in nonlinear optical systems. Emphasis is on passive (non-laser) systems that exhibit reversible bistability with input intensity as the hysteresis variable, along with the physics and the potential applications of such systems for nonlinear optical signal processing. This book consists of seven chapters and begins with a historical overview of optical bistability in lasers and passive systems. The next chapter describes steady-state theories of optical bistability, including the Bonifacio-Lugiato model, as we

  8. Manipulation of Self-Assembled Microparticle Chains by Electroosmotic Flow Assisted Electrorotation in an Optoelectronic Device

    Directory of Open Access Journals (Sweden)

    Xiaolu Zhu

    2015-09-01

    Full Text Available A method incorporating the optically induced electrorotation (OER and alternating current electroosmotic (ACEO effects, for the formation and motion control of microparticle chains, is numerically and experimentally demonstrated. In this method, both the rotating electric field and ACEO fluid roll are generated around the border between light and dark area of the fluidic chamber in an optoelectronic tweezers (OET device. The experimental results show that the particle chains can self-rotate in their pitch axes under the rotating electric field produced due to the different impedances of the photoconductive layer in light and dark areas, and have a peak self-rotating rate at around 1 MHz. The orbital movement of entire particle chain around the center of ACEO fluid roll can be achieved from 0.5 to 600 kHz. The strength of OER motion and ACEO-caused orbital movement of particle chains can be adjusted by changing the frequency of alternating current (AC voltage. This non-contact method has the potential for spatially regulating the posture, orientation and position of microparticle chains.

  9. Bilinear forms and soliton solutions for a fourth-order variable-coefficient nonlinear Schrödinger equation in an inhomogeneous Heisenberg ferromagnetic spin chain or an alpha helical protein

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jin-Wei; Gao, Yi-Tian, E-mail: gaoyt163@163.com; Wang, Qi-Min; Su, Chuan-Qi; Feng, Yu-Jie; Yu, Xin

    2016-01-15

    In this paper, a fourth-order variable-coefficient nonlinear Schrödinger equation is studied, which might describe a one-dimensional continuum anisotropic Heisenberg ferromagnetic spin chain with the octuple–dipole interaction or an alpha helical protein with higher-order excitations and interactions under continuum approximation. With the aid of auxiliary function, we derive the bilinear forms and corresponding constraints on the variable coefficients. Via the symbolic computation, we obtain the Lax pair, infinitely many conservation laws, one-, two- and three-soliton solutions. We discuss the influence of the variable coefficients on the solitons. With different choices of the variable coefficients, we obtain the parabolic, cubic, and periodic solitons, respectively. We analyse the head-on and overtaking interactions between/among the two and three solitons. Interactions between a bound state and a single soliton are displayed with different choices of variable coefficients. We also derive the quasi-periodic formulae for the three cases of the bound states.

  10. Exploration Supply Chain Simulation

    Science.gov (United States)

    2008-01-01

    The Exploration Supply Chain Simulation project was chartered by the NASA Exploration Systems Mission Directorate to develop a software tool, with proper data, to quantitatively analyze supply chains for future program planning. This tool is a discrete-event simulation that uses the basic supply chain concepts of planning, sourcing, making, delivering, and returning. This supply chain perspective is combined with other discrete or continuous simulation factors. Discrete resource events (such as launch or delivery reviews) are represented as organizational functional units. Continuous resources (such as civil service or contractor program functions) are defined as enabling functional units. Concepts of fixed and variable costs are included in the model to allow the discrete events to interact with cost calculations. The definition file is intrinsic to the model, but a blank start can be initiated at any time. The current definition file is an Orion Ares I crew launch vehicle. Parameters stretch from Kennedy Space Center across and into other program entities (Michaud Assembly Facility, Aliant Techsystems, Stennis Space Center, Johnson Space Center, etc.) though these will only gain detail as the file continues to evolve. The Orion Ares I file definition in the tool continues to evolve, and analysis from this tool is expected in 2008. This is the first application of such business-driven modeling to a NASA/government-- aerospace contractor endeavor.

  11. Chain Dynamics in Magnetorheological Suspensions

    Science.gov (United States)

    Gast, A. P.; Furst, E. M.

    1999-01-01

    Magnetorheological (MR) suspensions are composed of colloidal particles which acquire dipole moments when subjected to an external magnetic field. At sufficient field strengths and concentrations, the dipolar particles rapidly aggregate to form long chains. Subsequent lateral cross-linking of the dipolar chains is responsible for a rapid liquid-to-solid-like rheological transition. The unique, magnetically-activated rheological properties of MR suspensions make them ideal for interfacing mechanical systems to electronic controls. Additionally, the ability to experimentally probe colloidal suspensions interacting through tunable anisotropic potentials is of fundamental interest. Our current experimental work has focused on understanding the fluctuations of dipolar chains. It has been proposed by Halsey and Toor (HT) that the strong Landau-Peierls thermal fluctuations of dipolar chains could be responsible for long-range attractions between chains. Such interactions will govern the long-time relaxation of MR suspensions. We have synthesized monodisperse neutrally buoyant MR suspensions by density matching stabilized ferrofluid emulsion droplets with D2O. This allows us to probe the dynamics of the dipolar chains using light scattering without gravitational, interfacial, and polydispersity effects to resolve the short-wavelength dynamics of the dipolar chains. We used diffusing wave spectroscopy to measure these dynamics. The particle displacements at short times that show an independence to the field strength, but at long times exhibit a constrained, sub-diffusive motion that slows as the dipole strength is increased. The experiments are in good qualitative agreement with Brownian dynamics simulations of dipolar chains. Although there have been several important and detailed studies of the structure and interactions in MR suspensions, there has not been conclusive evidence that supports or contradicts the HT model prediction that long-range interactions exist between

  12. Primitive-path statistics of entangled polymers: mapping multi-chain simulations onto single-chain mean-field models

    International Nuclear Information System (INIS)

    Steenbakkers, Rudi J A; Schieber, Jay D; Tzoumanekas, Christos; Li, Ying; Liu, Wing Kam; Kröger, Martin

    2014-01-01

    We present a method to map the full equilibrium distribution of the primitive-path (PP) length, obtained from multi-chain simulations of polymer melts, onto a single-chain mean-field ‘target’ model. Most previous works used the Doi–Edwards tube model as a target. However, the average number of monomers per PP segment, obtained from multi-chain PP networks, has consistently shown a discrepancy of a factor of two with respect to tube-model estimates. Part of the problem is that the tube model neglects fluctuations in the lengths of PP segments, the number of entanglements per chain and the distribution of monomers among PP segments, while all these fluctuations are observed in multi-chain simulations. Here we use a recently proposed slip-link model, which includes fluctuations in all these variables as well as in the spatial positions of the entanglements. This turns out to be essential to obtain qualitative and quantitative agreement with the equilibrium PP-length distribution obtained from multi-chain simulations. By fitting this distribution, we are able to determine two of the three parameters of the model, which govern its equilibrium properties. This mapping is executed for four different linear polymers and for different molecular weights. The two parameters are found to depend on chemistry, but not on molecular weight. The model predicts a constant plateau modulus minus a correction inversely proportional to molecular weight. The value for well-entangled chains, with the parameters determined ab initio, lies in the range of experimental data for the materials investigated. (paper)

  13. Variable Gap Undulator for 1.5-48 Kev Free Electron Laser at Linac Coherent Light Source

    International Nuclear Information System (INIS)

    2011-01-01

    We study the feasibility of generating femtosecond duration Free-Electron Laser with a variable photon energy from 1.5 to 48 keV, using an electron bunch with the same characteristics of the LINAC Coherent Light Source (LCLS) bunch, and a planar undulator with additional focusing. We assume that the electron bunch energy can be changed, and the undulator has a variable gap, allowing a variable undulator parameter. It is assumed to be operated in an ultra-low charge and ultra-short pulse regime. We study the feasibility of a tunable, short pulse, X-ray FEL with photon energy from 1.5 to 48 keV, using an electron beam like the one in the LCLS and a 2:5 cm period, variable gap, planar undulator. The beam energy changes from 4.6 to 13.8 GeV, the electorn charge is kept at 10 pC, and the undulator parameter varies from 1 to 3. The undulator length needed to saturate the 48 keV FEL is about 55 m, with a peak power around 5 GW. At longer wavelength the saturation length is as short as 15 m, and the peak power around 20 GW. The results from the analytical models and the GENESIS simulations show that the system is feasible. The large wavelength range, full tunability and short, few femtosecond pulses, together with the large peak power, would provide a powerful research tool.

  14. Residue-Specific Side-Chain Polymorphisms via Particle Belief Propagation.

    Science.gov (United States)

    Ghoraie, Laleh Soltan; Burkowski, Forbes; Li, Shuai Cheng; Zhu, Mu

    2014-01-01

    Protein side chains populate diverse conformational ensembles in crystals. Despite much evidence that there is widespread conformational polymorphism in protein side chains, most of the X-ray crystallography data are modeled by single conformations in the Protein Data Bank. The ability to extract or to predict these conformational polymorphisms is of crucial importance, as it facilitates deeper understanding of protein dynamics and functionality. In this paper, we describe a computational strategy capable of predicting side-chain polymorphisms. Our approach extends a particular class of algorithms for side-chain prediction by modeling the side-chain dihedral angles more appropriately as continuous rather than discrete variables. Employing a new inferential technique known as particle belief propagation, we predict residue-specific distributions that encode information about side-chain polymorphisms. Our predicted polymorphisms are in relatively close agreement with results from a state-of-the-art approach based on X-ray crystallography data, which characterizes the conformational polymorphisms of side chains using electron density information, and has successfully discovered previously unmodeled conformations.

  15. Photochemical decomposition of perfluorooctanoic acid in aqueous periodate with VUV and UV light irradiation

    International Nuclear Information System (INIS)

    Cao, M.H.; Wang, B.B.; Yu, H.S.; Wang, L.L.; Yuan, S.H.; Chen, J.

    2010-01-01

    The photochemical decomposition of perfluorooctanoic acid (PFOA) in aqueous periodate (IO 4 - ) was investigated under two types of low-pressure mercury lamps: one emits at 254 nm light (UV light) and the other emits both 254 nm and 185 nm light (VUV light). PFOA decomposed efficiently under VUV light irradiation while it decomposed poorly under UV light irradiation. The addition of IO 4 - significantly increased the rate of decomposition and defluorination of PFOA irradiated with UV light whereas it decreased both processes under VUV irradiation. Reactive radical (IO 3 ·) generated by photolysis of IO 4 - initiated the oxidation of PFOA in UV process. Aquated electrons (e aq - ), generated from water homolysis, scavenged IO 4 - resulting in decrease of reactive radical species production and PFOA decomposition. The shorter-chain perfluorocarboxylic acids (PFCAs) formed in a stepwise manner from long-chain PFCAs.

  16. Quantification of rapid Myosin regulatory light chain phosphorylation using high-throughput in-cell Western assays: comparison to Western immunoblots.

    Directory of Open Access Journals (Sweden)

    Hector N Aguilar

    2010-04-01

    Full Text Available Quantification of phospho-proteins (PPs is crucial when studying cellular signaling pathways. Western immunoblotting (WB is commonly used for the measurement of relative levels of signaling intermediates in experimental samples. However, WB is in general a labour-intensive and low-throughput technique. Because of variability in protein yield and phospho-signal preservation during protein harvesting, and potential loss of antigen during protein transfer, WB provides only semi-quantitative data. By comparison, the "in-cell western" (ICW technique has high-throughput capacity and requires less extensive sample preparation. Thus, we compared the ICW technique to WB for measuring phosphorylated myosin regulatory light chain (PMLC(20 in primary cultures of uterine myocytes to assess their relative specificity, sensitivity, precision, and quantification of biologically relevant responses.ICWs are cell-based microplate assays for quantification of protein targets in their cellular context. ICWs utilize a two-channel infrared (IR scanner (Odyssey(R to quantify signals arising from near-infrared (NIR fluorophores conjugated to secondary antibodies. One channel is dedicated to measuring the protein of interest and the second is used for data normalization of the signal in each well of the microplate. Using uterine myocytes, we assessed oxytocin (OT-stimulated MLC(20 phosphorylation measured by ICW and WB, both using NIR fluorescence. ICW and WB data were comparable regarding signal linearity, signal specificity, and time course of phosphorylation response to OT.ICW and WB yield comparable biological data. The advantages of ICW over WB are its high-throughput capacity, improved precision, and reduced sample preparation requirements. ICW might provide better sensitivity and precision with low-quantity samples or for protocols requiring large numbers of samples. These features make the ICW technique an excellent tool for the study of phosphorylation endpoints

  17. LEAN HEALTHCARE SUPPLY CHAIN MANAGEMENT: MINIMIZING WASTE AND COSTS

    Directory of Open Access Journals (Sweden)

    Catia M L Machado

    2014-12-01

    Full Text Available The purpose of this research is to investigate the management models applied in the supply chain providing services in healthcare organizations, considering the lenses of lean. The aim of this is to develop a model of supply chain management focusing on the identification and minimization of waste, assisting in decision making and contributing to the quality of services and as a consequence the reduction of the costs involved in healthcare supply chain. The philosophies of continuous improvement and lean techniques have a role to play in helping healthcare to provide quality service and support to reduce costs in the current budget constraints. In the supply chain of hospitals the financial costs can be around 40% of its budget (MASOUMI et al. 2012; SOUZA et al., 2013. This article sheds light on the improvement in decision making and the effect of reducing costs in the healthcare supply chain. In this sense, the research intend to expand knowledge related to supply chain management in the area of ​​provision of healthcare services through the use of the philosophy of continuous improvement and lean principles, helping healthcare to provide quality service within their current budget constraints.

  18. Analysis of the response of a photovoltaic module subjected to pulsating light of variable duty cycle

    International Nuclear Information System (INIS)

    Zuñiga-Reyes, Marco A.; Sevilla-Camacho, P.Y.; Robles-Ocampo, J.B.; Lopez-Villarea, S. A.

    2017-01-01

    The present work analyzes the time domain response of polycrystalline and amorphous silicon modules subjected to a pulsed light signal, applied under conditions of darkness and controlled temperature. The applied light has a wavelength of 625 nm, a constant power of 5 Watts, a constant frequency of 10 kHz and a variable duty cycle. The response of the modules was analyzed in both direct current (DC) and alternating current (AC). The results of the research showed differences between the waveform and the amplitude of the output voltage of each of the manufacturing technologies of the modules. To validate the obtained results, the simulation of the response of a solar cell using its equivalent circuit in CA was performed. From the experimental and simulation tests it is observed that the relation between the duty cycle and the response of the modules of different technologies can be used for the monitoring and detection of faults or for the determination of the components of the AC equivalent circuit from the solar cells. (author)

  19. The Atomic Views of Flat Supply Chains in China

    Directory of Open Access Journals (Sweden)

    Sekhar Chattopadhyay

    2010-09-01

    Full Text Available China's domestic supply chain networks are getting flat and unbalanced despite its spectacular growth and rise to the enviable position in the global supply chain arena in recent times. The aftermath of continued investment explosion, especially in the coastal areas of the mainland, calls for an interwoven relationship of Chinese companies with the rest of the global supply chains. However, with new information and communication technologies, the real-time problems arising from this flattened supply chains are much more complex, multifaceted and multidimensional. China needs to re-think and re-focus on better alignment to the western values and cultures while managing its global business activities. This paper discusses four recently developed enterprise models in the light of several case studies conducted recently in Australia, China and India to characterise these new flat supply chains: People-Centric, Molecular Organization, Globally Dispersed and Disaggregated Value Chain. These, apparently different but inherently similar models have a vibrant architecture and system behaviour in their core and propose an alternative approach to address challenges of unbalanced domestic flat supply chains in China and helps the Chinese manufacturers to explore an approach to embrace Western values and cultures by enlarging their sphere of influence.

  20. Removal of a C-terminal serine residue proximal to the inter-chain disulfide bond of a human IgG1 lambda light chain mediates enhanced antibody stability and antibody dependent cell-mediated cytotoxicity

    Science.gov (United States)

    Shen, Yang; Zeng, Lin; Zhu, Aiping; Blanc, Tim; Patel, Dipa; Pennello, Anthony; Bari, Amtul; Ng, Stanley; Persaud, Kris; Kang, Yun (Kenneth); Balderes, Paul; Surguladze, David; Hindi, Sagit; Zhou, Qinwei; Ludwig, Dale L.; Snavely, Marshall

    2013-01-01

    Optimization of biophysical properties is a critical success factor for the developability of monoclonal antibodies with potential therapeutic applications. The inter-domain disulfide bond between light chain (Lc) and heavy chain (Hc) in human IgG1 lends structural support for antibody scaffold stability, optimal antigen binding, and normal Fc function. Recently, human IgG1λ has been suggested to exhibit significantly greater susceptibility to reduction of the inter Lc-Hc disulfide bond relative to the same disulfide bond in human IgG1κ. To understand the molecular basis for this observed difference in stability, the sequence and structure of human IgG1λ and human IgG1κ were compared. Based on this Lc comparison, three single mutations were made in the λ Lc proximal to the cysteine residue, which forms a disulfide bond with the Hc. We determined that deletion of S214 (dS) improved resistance of the association between Lc and Hc to thermal stress. In addition, deletion of this terminal serine from the Lc of IgG1λ provided further benefit, including an increase in stability at elevated pH, increased yield from transient transfection, and improved in vitro antibody dependent cell-mediated cytotoxicity (ADCC). These observations support the conclusion that the presence of the terminal serine of the λ Lc creates a weaker inter-chain disulfide bond between the Lc and Hc, leading to slightly reduced stability and a potential compromise in IgG1λ function. Our data from a human IgG1λ provide a basis for further investigation of the effects of deleting terminal serine from λLc on the stability and function of other human IgG1λ antibodies. PMID:23567210

  1. Supramolecular Nanoparticles via Single-Chain Folding Driven by Ferrous Ions.

    Science.gov (United States)

    Wang, Fei; Pu, Hongting; Jin, Ming; Wan, Decheng

    2016-02-01

    Single-chain nanoparticles can be obtained via single-chain folding assisted by intramolecular crosslinking reversibly or irreversibly. Single-chain folding is also an efficient route to simulate biomacromolecules. In present study, poly(N-hydroxyethylacrylamide-co-4'-(propoxy urethane ethyl acrylate)-2,2':6',2''-terpyridine) (P(HEAm-co-EMA-Tpy)) is synthesized via reversible addition fragmentation chain transfer polymerization. Single-chain folding and intramolecular crosslinking of P(HEAm-co-EMA-Tpy) are achieved via metal coordination chemistry. The intramolecular interaction is characterized on ultraviolet/visible spectrophotometer (UV-vis spectroscopy), proton nuclear magnetic resonance ((1)H NMR), and differential scanning calorimetry (DSC). The supramolecular crosslinking mediated by Fe(2+) plays an important role in the intramolecular collapsing of the single-chain and the formation of the nanoparticles. The size and morphology of the nanoparticles can be controlled reversibly via metal coordination chemistry, which can be characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and atomic force microscope (AFM). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. Consistent energy barrier distributions in magnetic particle chains

    International Nuclear Information System (INIS)

    Laslett, O.; Ruta, S.; Chantrell, R.W.; Barker, J.; Friedman, G.; Hovorka, O.

    2016-01-01

    We investigate long-time thermal activation behaviour in magnetic particle chains of variable length. Chains are modelled as Stoner–Wohlfarth particles coupled by dipolar interactions. Thermal activation is described as a hopping process over a multidimensional energy landscape using the discrete orientation model limit of the Landau–Lifshitz–Gilbert dynamics. The underlying master equation is solved by diagonalising the associated transition matrix, which allows the evaluation of distributions of time scales of intrinsic thermal activation modes and their energy representation. It is shown that as a result of the interaction dependence of these distributions, increasing the particle chain length can lead to acceleration or deceleration of the overall relaxation process depending on the initialisation procedure.

  3. Honest Importance Sampling with Multiple Markov Chains.

    Science.gov (United States)

    Tan, Aixin; Doss, Hani; Hobert, James P

    2015-01-01

    Importance sampling is a classical Monte Carlo technique in which a random sample from one probability density, π 1 , is used to estimate an expectation with respect to another, π . The importance sampling estimator is strongly consistent and, as long as two simple moment conditions are satisfied, it obeys a central limit theorem (CLT). Moreover, there is a simple consistent estimator for the asymptotic variance in the CLT, which makes for routine computation of standard errors. Importance sampling can also be used in the Markov chain Monte Carlo (MCMC) context. Indeed, if the random sample from π 1 is replaced by a Harris ergodic Markov chain with invariant density π 1 , then the resulting estimator remains strongly consistent. There is a price to be paid however, as the computation of standard errors becomes more complicated. First, the two simple moment conditions that guarantee a CLT in the iid case are not enough in the MCMC context. Second, even when a CLT does hold, the asymptotic variance has a complex form and is difficult to estimate consistently. In this paper, we explain how to use regenerative simulation to overcome these problems. Actually, we consider a more general set up, where we assume that Markov chain samples from several probability densities, π 1 , …, π k , are available. We construct multiple-chain importance sampling estimators for which we obtain a CLT based on regeneration. We show that if the Markov chains converge to their respective target distributions at a geometric rate, then under moment conditions similar to those required in the iid case, the MCMC-based importance sampling estimator obeys a CLT. Furthermore, because the CLT is based on a regenerative process, there is a simple consistent estimator of the asymptotic variance. We illustrate the method with two applications in Bayesian sensitivity analysis. The first concerns one-way random effects models under different priors. The second involves Bayesian variable

  4. CSF neurofilament light chain and phosphorylated tau 181 predict disease progression in PSP.

    Science.gov (United States)

    Rojas, Julio C; Bang, Jee; Lobach, Iryna V; Tsai, Richard M; Rabinovici, Gil D; Miller, Bruce L; Boxer, Adam L

    2018-01-23

    To determine the ability of CSF biomarkers to predict disease progression in progressive supranuclear palsy (PSP). We compared the ability of baseline CSF β-amyloid 1-42 , tau, phosphorylated tau 181 (p-tau), and neurofilament light chain (NfL) concentrations, measured by INNO-BIA AlzBio3 or ELISA, to predict 52-week changes in clinical (PSP Rating Scale [PSPRS] and Schwab and England Activities of Daily Living [SEADL]), neuropsychological, and regional brain volumes on MRI using linear mixed effects models controlled for age, sex, and baseline disease severity, and Fisher F density curves to compare effect sizes in 50 patients with PSP. Similar analyses were done using plasma NfL measured by single molecule arrays in 141 patients. Higher CSF NfL concentration predicted more rapid decline (biomarker × time interaction) over 52 weeks in PSPRS ( p = 0.004, false discovery rate-corrected) and SEADL ( p = 0.008), whereas lower baseline CSF p-tau predicted faster decline on PSPRS ( p = 0.004). Higher CSF tau concentrations predicted faster decline by SEADL ( p = 0.004). The CSF NfL/p-tau ratio was superior for predicting change in PSPRS, compared to p-tau ( p = 0.003) or NfL ( p = 0.001) alone. Higher NfL concentrations in CSF or blood were associated with greater superior cerebellar peduncle atrophy (fixed effect, p ≤ 0.029 and 0.008, respectively). Both CSF p-tau and NfL correlate with disease severity and rate of disease progression in PSP. The inverse correlation of p-tau with disease severity suggests a potentially different mechanism of tau pathology in PSP as compared to Alzheimer disease. Copyright © 2017 American Academy of Neurology.

  5. Can light make us bright? Effects of light on cognition and sleep

    NARCIS (Netherlands)

    Chellappa, Sarah Laxhmi; Gordijn, Marijke C. M.; Cajochen, Christian; VanDongen, HPA; Kerkhof, GA

    2011-01-01

    Light elicits robust nonvisual effects on numerous physiological and behavioral variables, such as the human sleep-wake cycle and cognitive performance. Light effects crucially rely on properties such as dose, duration, timing, and wavelength. Recently, the use of methods such as fMRI to assess

  6. The nebular variables

    CERN Document Server

    Glasby, John S

    1974-01-01

    The Nebular Variables focuses on the nebular variables and their characteristics. Discussions are organized by type of nebular variable, namely, RW Aurigae stars, T Orionis stars, T Tauri stars, and peculiar nebular objects. Topics range from light variations of the stars to their spectroscopic and physical characteristics, spatial distribution, interaction with nebulosity, and evolutionary features. This volume is divided into four sections and consists of 25 chapters, the first of which provides general information on nebular variables, including their stellar associations and their classifi

  7. Neutralization of botulinum neurotoxin by a human monoclonal antibody specific for the catalytic light chain.

    Directory of Open Access Journals (Sweden)

    Sharad P Adekar

    2008-08-01

    Full Text Available Botulinum neurotoxins (BoNT are a family of category A select bioterror agents and the most potent biological toxins known. Cloned antibody therapeutics hold considerable promise as BoNT therapeutics, but the therapeutic utility of antibodies that bind the BoNT light chain domain (LC, a metalloprotease that functions in the cytosol of cholinergic neurons, has not been thoroughly explored.We used an optimized hybridoma method to clone a fully human antibody specific for the LC of serotype A BoNT (BoNT/A. The 4LCA antibody demonstrated potent in vivo neutralization when administered alone and collaborated with an antibody specific for the HC. In Neuro-2a neuroblastoma cells, the 4LCA antibody prevented the cleavage of the BoNT/A proteolytic target, SNAP-25. Unlike an antibody specific for the HC, the 4LCA antibody did not block entry of BoNT/A into cultured cells. Instead, it was taken up into synaptic vesicles along with BoNT/A. The 4LCA antibody also directly inhibited BoNT/A catalytic activity in vitro.An antibody specific for the BoNT/A LC can potently inhibit BoNT/A in vivo and in vitro, using mechanisms not previously associated with BoNT-neutralizing antibodies. Antibodies specific for BoNT LC may be valuable components of an antibody antidote for BoNT exposure.

  8. Influence of chain topology and bond potential on the glass transition of polymer chains simulated with the bond fluctuation model

    International Nuclear Information System (INIS)

    Freire, J J

    2008-01-01

    The bond fluctuation model with a bond potential has been applied to investigation of the glass transition of linear chains and chains with a regular disposition of small branches. Cooling and subsequent heating curves are obtained for the chain energies and also for the mean acceptance probability of a bead jump. In order to mimic different trends to vitrification, a factor B gauging the strength of the bond potential with respect to the long-range potential (i.e. the intramolecular or intermolecular potential between indirectly bonded beads) has been introduced. (A higher value of B leads to a preference for the highest bond lengths and a higher total energy, implying a greater tendency to vitrify.) Different cases have been considered for linear chains: no long-range potential, no bond potential and several choices for B. Furthermore, two distinct values of B have been considered for alternate bonds in linear chains. In the case of the branched chains, mixed models with different values of B for bonds in the main chain and in the branches have also been investigated. The possible presence of ordering or crystallization has been characterized by calculating the collective light scattering function of the different samples after annealing at a convenient temperature below the onset of the abrupt change in the curves associated with a thermodynamic transition. It is concluded that ordering is inherited more efficiently in the systems with branched chains and also for higher values of B. The branched molecules with the highest B values in the main chain bonds exhibit two distinct transitions in the heating curves, which may be associated with two glass transitions. This behavior has been detected experimentally for chains with relatively long flexible branches

  9. Influence of chain topology and bond potential on the glass transition of polymer chains simulated with the bond fluctuation model

    Energy Technology Data Exchange (ETDEWEB)

    Freire, J J [Departamento de Ciencias y Tecnicas FisicoquImicas, Facultad de Ciencias, Universidad Nacional de Educacion a Distancia (UNED), Senda del Rey 9, 28040 Madrid (Spain)], E-mail: jfreire@invi.uned.es

    2008-07-16

    The bond fluctuation model with a bond potential has been applied to investigation of the glass transition of linear chains and chains with a regular disposition of small branches. Cooling and subsequent heating curves are obtained for the chain energies and also for the mean acceptance probability of a bead jump. In order to mimic different trends to vitrification, a factor B gauging the strength of the bond potential with respect to the long-range potential (i.e. the intramolecular or intermolecular potential between indirectly bonded beads) has been introduced. (A higher value of B leads to a preference for the highest bond lengths and a higher total energy, implying a greater tendency to vitrify.) Different cases have been considered for linear chains: no long-range potential, no bond potential and several choices for B. Furthermore, two distinct values of B have been considered for alternate bonds in linear chains. In the case of the branched chains, mixed models with different values of B for bonds in the main chain and in the branches have also been investigated. The possible presence of ordering or crystallization has been characterized by calculating the collective light scattering function of the different samples after annealing at a convenient temperature below the onset of the abrupt change in the curves associated with a thermodynamic transition. It is concluded that ordering is inherited more efficiently in the systems with branched chains and also for higher values of B. The branched molecules with the highest B values in the main chain bonds exhibit two distinct transitions in the heating curves, which may be associated with two glass transitions. This behavior has been detected experimentally for chains with relatively long flexible branches.

  10. Making Supply Chains Resilient to Floods Using a Bayesian Network

    Science.gov (United States)

    Haraguchi, M.

    2015-12-01

    Natural hazards distress the global economy by disrupting the interconnected supply chain networks. Manufacturing companies have created cost-efficient supply chains by reducing inventories, streamlining logistics and limiting the number of suppliers. As a result, today's supply chains are profoundly susceptible to systemic risks. In Thailand, for example, the GDP growth rate declined by 76 % in 2011 due to prolonged flooding. Thailand incurred economic damage including the loss of USD 46.5 billion, approximately 70% of which was caused by major supply chain disruptions in the manufacturing sector. Similar problems occurred after the Great East Japan Earthquake and Tsunami in 2011, the Mississippi River floods and droughts during 2011 - 2013, and Hurricane Sandy in 2012. This study proposes a methodology for modeling supply chain disruptions using a Bayesian network analysis (BNA) to estimate expected values of countermeasures of floods, such as inventory management, supplier management and hard infrastructure management. We first performed a spatio-temporal correlation analysis between floods and extreme precipitation data for the last 100 years at a global scale. Then we used a BNA to create synthetic networks that include variables associated with the magnitude and duration of floods, major components of supply chains and market demands. We also included decision variables of countermeasures that would mitigate potential losses caused by supply chain disruptions. Finally, we conducted a cost-benefit analysis by estimating the expected values of these potential countermeasures while conducting a sensitivity analysis. The methodology was applied to supply chain disruptions caused by the 2011 Thailand floods. Our study demonstrates desirable typical data requirements for the analysis, such as anonymized supplier network data (i.e. critical dependencies, vulnerability information of suppliers) and sourcing data(i.e. locations of suppliers, and production rates and

  11. Surface mu heavy chain signals down-regulation of the V(D)J-recombinase machinery in the absence of surrogate light chain components.

    Science.gov (United States)

    Galler, Gunther R; Mundt, Cornelia; Parker, Mathew; Pelanda, Roberta; Mårtensson, Inga-Lill; Winkler, Thomas H

    2004-06-07

    Early B cell development is characterized by stepwise, ordered rearrangement of the immunoglobulin (Ig) heavy (HC) and light (LC) chain genes. Only one of the two alleles of these genes is used to produce a receptor, a phenomenon referred to as allelic exclusion. It has been suggested that pre-B cell receptor (pre-BCR) signals are responsible for down-regulation of the VDJH-recombinase machinery (Rag1, Rag2, and terminal deoxynucleotidyl transferase [TdT]), thereby preventing further rearrangement on the second HC allele. Using a mouse model, we show that expression of an inducible muHC transgene in Rag2-/- pro-B cells induces down-regulation of the following: (a) TdT protein, (b) a transgenic green fluorescent protein reporter reflecting endogenous Rag2 expression, and (c) Rag1 primary transcripts. Similar effects were also observed in the absence of surrogate LC (SLC) components, but not in the absence of the signaling subunit Ig-alpha. Furthermore, in wild-type mice and in mice lacking either lambda5, VpreB1/2, or the entire SLC, the TdT protein is down-regulated in muHC+LC- pre-B cells. Surprisingly, muHC without LC is expressed on the surface of pro-/pre-B cells from lambda5-/-, VpreB1-/-VpreB2-/-, and SLC-/- mice. Thus, SLC or LC is not required for muHC cell surface expression and signaling in these cells. Therefore, these findings offer an explanation for the occurrence of HC allelic exclusion in mice lacking SLC components.

  12. Interaction in endothelium of non-muscular myosin light-chain kinase and the NF-κB pathway is critical to lipopolysaccharide-induced vascular hyporeactivity.

    Science.gov (United States)

    Recoquillon, Sylvain; Carusio, Nunzia; Lagrue-Lakhal, Anne-Hélène; Tual-Chalot, Simon; Filippelli, Amelia; Andriantsitohaina, Ramaroson; Martinez, M Carmen

    2015-10-01

    During sepsis, endothelial barrier dysfunction contributes to cardiovascular failure, mainly through the release of oxidative metabolites by penetrant leukocytes. We reported the non-muscular isoform of myosin light chain kinase (nmMLCK) playing a pivotal role in endotoxin shock injury associated with oxidative and nitrative stresses, and vascular hyporeactivity. The present study was aimed at understanding the molecular mechanism of lipopolysaccharide (LPS)-induced vascular alterations as well as studying a probable functional association of nmMLCK with nuclear factor κ-light-chain enhancer of activated B cells (NF-κB). Aortic rings from mice were exposed in vitro to LPS and, then, vascular reactivity was measured. Human aortic endothelial cells (HAoECs) were incubated with LPS, and interaction of nmMLCK with NF-κB was analysed. We provide evidence that nmMLCK deletion prevents vascular hyporeactivity induced by in vitro LPS treatment but not endothelial dysfunction in the aorta. Deletion of nmMLCK inhibits LPS-induced NF-κB activation and increases nitric oxide (NO) release via induction of inducible NO synthase (iNOS) within the vascular wall. Also, removal of endothelium prevented both NF-κB and iNOS expression in aortic rings. Among the proinflammatory factors released by LPS-treated endothelial cells, interleukin-6 accounts for the induction of iNOS on smooth muscle cells in response to LPS. Of particular interest is the demonstration that, in HAoECs, LPS-induced NF-κB activation occurs via increased MLCK activity sensitive to the MLCK inhibitor, ML-7, and physical interactions between nmMLCK and NF-κB. We report for the first time on NF-κB as a novel partner of nmMLCK within endothelial cells. The present study demonstrates a pivotal role of nmMLCK in vascular inflammatory pathologies. © 2015 Authors; published by Portland Press Limited.

  13. Chain Plot: A Tool for Exploiting Bivariate Temporal Structures

    OpenAIRE

    Taylor, CC; Zempeni, A

    2004-01-01

    In this paper we present a graphical tool useful for visualizing the cyclic behaviour of bivariate time series. We investigate its properties and link it to the asymmetry of the two variables concerned. We also suggest adding approximate confidence bounds to the points on the plot and investigate the effect of lagging to the chain plot. We conclude our paper by some standard Fourier analysis, relating and comparing this to the chain plot.

  14. Durability of Materials in Pearl-Chain Bridges

    DEFF Research Database (Denmark)

    Lund, Mia Schou Møller

    . The construction of the Pearl-Chain arch is simple. The arch is assembled on its side, next to the road that the bridge will span, by placing a number of plane prefabricated Super-Light Decks that consist of lightweight aggregate concrete and conventional concrete, in the desired arch shape. Mortar joints are cast...... is stabilized by casting a fill material between the spandrel walls of the arch. Finally, the road surface is cast on top of the fill material. New bridges are designed for a service lifetime of at least 100 years. Hence, the specifications of the materials used in Pearl-Chain Bridges are high. This PhD study...... and pervious concrete were also investigated. The most suitable fill material for Pearl-Chain Bridges depends on the particular bridge design; the results obtained and presented in the present PhD study provide guidance on how to decide which fill material is most suitable regarding strength, permeability...

  15. Machine learning search for variable stars

    Science.gov (United States)

    Pashchenko, Ilya N.; Sokolovsky, Kirill V.; Gavras, Panagiotis

    2018-04-01

    Photometric variability detection is often considered as a hypothesis testing problem: an object is variable if the null hypothesis that its brightness is constant can be ruled out given the measurements and their uncertainties. The practical applicability of this approach is limited by uncorrected systematic errors. We propose a new variability detection technique sensitive to a wide range of variability types while being robust to outliers and underestimated measurement uncertainties. We consider variability detection as a classification problem that can be approached with machine learning. Logistic Regression (LR), Support Vector Machines (SVM), k Nearest Neighbours (kNN), Neural Nets (NN), Random Forests (RF), and Stochastic Gradient Boosting classifier (SGB) are applied to 18 features (variability indices) quantifying scatter and/or correlation between points in a light curve. We use a subset of Optical Gravitational Lensing Experiment phase two (OGLE-II) Large Magellanic Cloud (LMC) photometry (30 265 light curves) that was searched for variability using traditional methods (168 known variable objects) as the training set and then apply the NN to a new test set of 31 798 OGLE-II LMC light curves. Among 205 candidates selected in the test set, 178 are real variables, while 13 low-amplitude variables are new discoveries. The machine learning classifiers considered are found to be more efficient (select more variables and fewer false candidates) compared to traditional techniques using individual variability indices or their linear combination. The NN, SGB, SVM, and RF show a higher efficiency compared to LR and kNN.

  16. Efficient Synthesis of Single-Chain Polymer Nanoparticles via Amide Formation

    Directory of Open Access Journals (Sweden)

    Ana Sanchez-Sanchez

    2015-01-01

    Full Text Available Single-chain technology (SCT allows the transformation of individual polymer chains to folded/collapsed unimolecular soft nanoparticles. In this work we contribute to the enlargement of the SCT toolbox by demonstrating the efficient synthesis of single-chain polymer nanoparticles (SCNPs via intrachain amide formation. In particular, we exploit cross-linking between active methylene groups and isocyanate moieties as powerful “click” chemistry driving force for SCNP construction. By employing poly(methyl methacrylate- (PMMA- based copolymers bearing β-ketoester units distributed randomly along the copolymer chains and bifunctional isocyanate cross-linkers, SCNPs were successfully synthesized at r.t. under appropriate reaction conditions. Characterization of the resulting SCNPs was carried out by means of a combination of techniques including size exclusion chromatography (SEC, infrared (IR spectroscopy, proton nuclear magnetic resonance (1H NMR spectroscopy, dynamic light scattering (DLS, and elemental analysis (EA.

  17. The Influence of New Colored Light Stimulation Methods on Heart Rate Variability, Temperature, and Well-Being: Results of a Pilot Study in Humans

    Directory of Open Access Journals (Sweden)

    Daniela Litscher

    2013-01-01

    Full Text Available Changes of light intensity of different colors can shift many physiological parameters and conditions like melatonin, alertness, body temperature, heart rate (HR, and heart rate variability (HRV. The aim of this pilot study was to investigate acute temperature, HR, HRV, and state of mind reactivities after illumination with red (631 nm and blue (456 nm light (illuminance 140 lux for both. Seven healthy volunteers (5 females, 2 males; mean age ± SD 34.1 ± 11.9 years were investigated at the Medical University of Graz, using new color light panels. Significant decreases were found only after 10 min blue light stimulation in nose temperature (P=0.046, HR (P<0.05, and total HRV (P=0.029, in association with a significant alteration of the emotional state (stress level score, P=0.006. However, red light stimulation of the same persons did not induce the same effects in these parameters. The effect of blue light as environmental stimulation on human health is not clarified in detail and needs further investigations.

  18. White Light Generation in Human Saliva

    Science.gov (United States)

    Santhosh, C.; Dharmadhikari, A. K.; Dharmadhikari, J. A.; Alti, K.; Mathur, D.

    2011-07-01

    Interaction of intense, femto-second pulses of infrared light (800 nm) with water generates white light supercontinuum due to nonlinear optical effects. This supercontinuum was found to be suppressed by the addition of alpha amylase, a major protein in the human saliva. We have studied the suppression of supper continuum by human saliva, collected from healthy subjects with and without smoking habits. Suppression of the blue-sided components was observed significantly in non-smokers saliva than chain smokers.

  19. Internal Light Source-Driven Photoelectrochemical 3D-rGO/Cellulose Device Based on Cascade DNA Amplification Strategy Integrating Target Analog Chain and DNA Mimic Enzyme.

    Science.gov (United States)

    Lan, Feifei; Liang, Linlin; Zhang, Yan; Li, Li; Ren, Na; Yan, Mei; Ge, Shenguang; Yu, Jinghua

    2017-11-01

    In this work, a chemiluminescence-driven collapsible greeting card-like photoelectrochemical lab-on-paper device (GPECD) with hollow channel was demonstrated, in which target-triggering cascade DNA amplification strategy was ingeniously introduced. The GPECD had the functions of reagents storage and signal collection, and the change of configuration could control fluidic path, reaction time and alterations in electrical connectivity. In addition, three-dimentional reduced graphene oxide affixed Au flower was in situ grown on paper cellulose fiber for achieving excellent conductivity and biocompatibility. The cascade DNA amplification strategy referred to the cyclic formation of target analog chain and its trigger action to hybridization chain reaction (HCR), leading to the formation of numerous hemin/G-quadruplex DNA mimic enzyme with the presence of hemin. Subjected to the catalysis of hemin/G-quadruplex, the strong chemiluminiscence of luminol-H 2 O 2 system was obtained, which then was used as internal light source to excite photoactive materials realizing the simplification of instrument. In this analyzing process, thrombin served as proof-of-concept, and the concentration of target was converted into the DNA signal output by the specific recognition of aptamer-protein and target analog chain recycling. The target analog chain was produced in quantity with the presence of target, which further triggered abundant HCR and introduced hemin/G-quadruplex into the system. The photocurrent signal was obtained after the nitrogen-doped carbon dots sensitized ZnO was stimulated by chemiluminescence. The proposed GPECD exhibited excellent specificity and sensitivity toward thrombin with a detection limit of 16.7 fM. This judiciously engineered GPECD paved a luciferous way for detecting other protein with trace amounts in bioanalysis and clinical biomedicine.

  20. Bloch Oscillations in the Chains of Artificial Atoms Dressed with Photons

    Directory of Open Access Journals (Sweden)

    Ilay Levie

    2018-06-01

    Full Text Available We present a model of one-dimensional chain of two-level artificial atoms driven with DC field and quantum light simultaneously in a strong coupling regime. The interaction of atoms with light leads to electron-photon entanglement (dressing of the atoms with light. The driving via dc field leads to the Bloch oscillations (BO in the chain of dressed atoms. We consider the mutual influence of dressing and BO and show that scenario of oscillations dramatically differs from predicted by the Jaynes-Cummings and Bloch-Zener models. We study the evolution of the population inversion, tunneling current, photon probability distribution, mean number of photons, and photon number variance, and show the influence of BO on the quantum-statistical characteristics of light. For example, the collapse-revivals picture and vacuum Rabi-oscillations are strongly modulated with Bloch frequency. As a result, quantum properties of light and degree of electron-photon entanglement become controllable via adiabatic dc field turning. On the other hand, the low-frequency tunneling current depends on the quantum light statistics (in particular, for coherent initial state it is modulated accordingly the collapse-revivals picture. The developed model is universal with respect to the physical origin of artificial atom and frequency range of atom-light interaction. The model is adapted to the 2D-heterostructures (THz frequencies, semiconductor quantum dots (optical range, and Josephson junctions (microwaves. The data for numerical simulations are taken from recently published experiments. The obtained results open a new way in quantum state engineering and nano-photonic spectroscopy.

  1. Nutritional status independently affects quality of life of patients with systemic immunoglobulin light-chain (AL) amyloidosis.

    Science.gov (United States)

    Caccialanza, Riccardo; Palladini, Giovanni; Klersy, Catherine; Cereda, Emanuele; Bonardi, Chiara; Cameletti, Barbara; Montagna, Elisabetta; Russo, Paola; Foli, Andrea; Milani, Paolo; Lavatelli, Francesca; Merlini, Giampaolo

    2012-03-01

    Nutritional status is an independent prognostic factor in immunoglobulin light-chain amyloidosis (AL), but its influence on quality of life (QoL) is unknown. The aim of this cross-sectional study was to investigate the association between nutritional status and QoL in AL patients at diagnosis. One hundred and fifty consecutive patients with biopsy-proven AL were assessed for nutritional status by anthropometry [body mass index, unintentional weight loss (WL) in the previous 6 months and mid-arm muscle circumference (MAMC)], biochemistry (serum prealbumin), and semiquantitative food intake at referral. QoL was assessed by the Medical Outcomes Study 36-item Short Form General Health Survey. The composite physical component summary (PCS) and the mental component summary (MCS) for AL outpatients were 36.2 ± 10.1 and 44.9 ± 11.3, respectively (p performance status, the number of organs involved, the severity of cardiac damage, C-reactive protein, energy intake, and WL, PCS was significantly lower for serum prealbumin Nutritional status independently affects QoL in AL patients since diagnosis. Nutritional evaluation should be integral part of the clinical assessment of AL patients. Nutritional support intervention trials are warranted in such patients' population.

  2. Customer involvement in greening the supply chain: an interpretive structural modeling methodology

    Science.gov (United States)

    Kumar, Sanjay; Luthra, Sunil; Haleem, Abid

    2013-04-01

    The role of customers in green supply chain management needs to be identified and recognized as an important research area. This paper is an attempt to explore the involvement aspect of customers towards greening of the supply chain (SC). An empirical research approach has been used to collect primary data to rank different variables for effective customer involvement in green concept implementation in SC. An interpretive structural-based model has been presented, and variables have been classified using matrice d' impacts croises- multiplication appliqué a un classement analysis. Contextual relationships among variables have been established using experts' opinions. The research may help practicing managers to understand the interaction among variables affecting customer involvement. Further, this understanding may be helpful in framing the policies and strategies to green SC. Analyzing interaction among variables for effective customer involvement in greening SC to develop the structural model in the Indian perspective is an effort towards promoting environment consciousness.

  3. Analysis of the multiple forms of the 20,000-dalton myosin light, chain from uterine arterial smooth muscles

    International Nuclear Information System (INIS)

    Barany, K.; Csabina, S.; Mougios, V.; Barany, M.

    1986-01-01

    2D gel electrophoresis resolved the light chain (LC) in four spots, three spots were phosphorylated. Phosphorylation was determined by densitometry (S) and [ 32 P]phosphate incorporation (P). Molar [ 32 P]phosphate incorporation was quantitated for each LC spot. Phosphorylation was low in resting or drug-relaxed muscles and high in contracting or stretched muscles. At low phosphorylation S > P, this discrepancy can be explained by the presence of unphosphorylated isoforms in the phosphorylated spots. Indeed, unphosphorylated uterine LC exhibited three spots on electrophoretograms (distribution: 0, 13, 7, 80%), whereas arterial LC showed two spots (0, 15, 0, 85%). At high phosphorylation P > S, this aberration is caused by diphosphorylation. In the intact tissue of uterus, the ratio of Thr-P to Ser-P, and the level of diphosphorylation are higher than in artery. The molecular weight and isoelectric points of uterine and arterial LC are the same, but the percentage distribution of the unphosphorylated isoforms, the molar phosphate incorporation in the phosphorylated spots, and the extent of diphosphorylation are different

  4. Outcome prediction in plasmacytoma of bone: a risk model utilizing bone marrow flow cytometry and light-chain analysis.

    Science.gov (United States)

    Hill, Quentin A; Rawstron, Andy C; de Tute, Ruth M; Owen, Roger G

    2014-08-21

    The purpose of this study was to use multiparameter flow cytometry to detect occult marrow disease (OMD) in patients with solitary plasmacytoma of bone and assess its value in predicting outcome. Aberrant phenotype plasma cells were demonstrable in 34 of 50 (68%) patients and comprised a median of 0.52% of bone marrow leukocytes. With a median follow-up of 3.7 years, 28 of 50 patients have progressed with a median time to progression (TTP) of 18 months. Progression was documented in 72% of patients with OMD vs 12.5% without (median TTP, 26 months vs not reached; P = .003). Monoclonal urinary light chains (ULC) were similarly predictive of outcome because progression was documented in 91% vs 44% without (median TTP, 16 vs 82 months; P < .001). By using both parameters, it was possible to define patients with an excellent outcome (lacking both OMD and ULC, 7.7% progression) and high-risk patients (OMD and/or ULC, 75% progression; P = .001). Trials of systemic therapy are warranted in high-risk patients. © 2014 by The American Society of Hematology.

  5. Natural Hazards and Supply Chain Disruptions

    Science.gov (United States)

    Haraguchi, M.

    2016-12-01

    Natural hazards distress the global economy through disruptions in supply chain networks. Moreover, despite increasing investment to infrastructure for disaster risk management, economic damages and losses caused by natural hazards are increasing. Manufacturing companies today have reduced inventories and streamlined logistics in order to maximize economic competitiveness. As a result, today's supply chains are profoundly susceptible to systemic risks, which are the risk of collapse of an entire network caused by a few node of the network. For instance, the prolonged floods in Thailand in 2011 caused supply chain disruptions in their primary industries, i.e. electronic and automotive industries, harming not only the Thai economy but also the global economy. Similar problems occurred after the Great East Japan Earthquake and Tsunami in 2011, the Mississippi River floods and droughts during 2011 - 2013, and the Earthquake in Kumamoto Japan in 2016. This study attempts to discover what kind of effective measures are available for private companies to manage supply chain disruptions caused by floods. It also proposes a method to estimate potential risks using a Bayesian network. The study uses a Bayesian network to create synthetic networks that include variables associated with the magnitude and duration of floods, major components of supply chains such as logistics, multiple layers of suppliers, warehouses, and consumer markets. Considering situations across different times, our study shows desirable data requirements for the analysis and effective measures to improve Value at Risk (VaR) for private enterprises and supply chains.

  6. Intensified training increases salivary free light chains in trained cyclists: Indication that training volume increases oral inflammation.

    Science.gov (United States)

    Heaney, Jennifer L J; Killer, Sophie C; Svendsen, Ida S; Gleeson, Michael; Campbell, John P

    2018-05-01

    Periods of short-term intensified training (IT) are often used by athletes during training cycles over the season and undergoing phases of increased physical stress may impact upon the immune system. This study investigated the effects of a period of IT on free light chains (FLCs) in saliva - an emerging immune biomarker of oral inflammation - and matched serum samples in well-trained athletes. It also examined if IT influences basal FLC levels and FLC flux during acute exercise. Highly trained male cyclists (n = 10) underwent a 9-day period of IT; before and after IT participants performed a 1 h time trial (TT) on a cycle ergometer, with blood and saliva samples collected pre- and post-exercise. FLCs were assessed in serum and saliva, and IgG, IgA, IgM and creatinine were also measured in serum. Weekly training volume increased by 143% (95% CI 114-172%), p training. Following IT, the cyclists demonstrated higher salivary FLC levels. Both salivary lambda FLC concentrations (p training, and we show for the first time that FLCs may have utility as a marker of exercise stress and oral health status. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Physical linkage of a human immunoglobulin heavy chain variable region gene segment to diversity and joining region elements

    International Nuclear Information System (INIS)

    Schroeder, H.W. Jr.; Walter, M.A.; Hofker, M.H.; Ebens, A.; Van Dijk, K.W.; Liao, L.C.; Cox, D.W.; Milner, E.C.B.; Perlmutter, R.M.

    1988-01-01

    Antibody genes are assembled from a series of germ-line gene segments that are juxtaposed during the maturation of B lymphocytes. Although diversification of the adult antibody repertoire results in large part from the combinatorial joining of these gene segments, a restricted set of antibody heavy chain variable (V H ), diversity (D H ), and joining (J H ) region gene segments appears preferentially in the human fetal repertoire. The authors report here that one of these early-expressed V H elements (termed V H 6) is the most 3' V H gene segment, positioned 77 kilobases on the 5' side of the J H locus and immediately adjacent to a set of previously described D H sequences. In addition to providing a physical map linking human V H , D H , and J H elements, these results support the view that the programmed development of the antibody V H repertoire is determined in part by the chromosomal position of these gene segments

  8. High production of llama variable heavy-chain antibody fragment (VHH) fused to various reader proteins by Aspergillus oryzae.

    Science.gov (United States)

    Hisada, Hiromoto; Tsutsumi, Hiroko; Ishida, Hiroki; Hata, Yoji

    2013-01-01

    Llama variable heavy-chain antibody fragment (VHH) fused to four different reader proteins was produced and secreted in culture medium by Aspergillus oryzae. These fusion proteins consisted of N-terminal reader proteins, VHH, and a C-terminal his-tag sequence which facilitated purification using one-step his-tag affinity chromatography. SDS-PAGE analysis of the deglycosylated purified fusion proteins confirmed that the molecular weight of each corresponded to the expected sum of VHH and the respective reader proteins. The apparent high molecular weight reader protein glucoamylase (GlaB) was found to be suitable for efficient VHH production. The GlaB-VHH-His protein bound its antigen, human chorionic gonadotropin, and was detectable by a new ELISA-based method using a coupled assay with glucoamylase, glucose oxidase, peroxidase, maltose, and 3,3',5,5'-tetramethylbenzidine as substrates. Addition of potassium phosphate to the culture medium induced secretion of 0.61 mg GlaB-VHH-His protein/ml culture medium in 5 days.

  9. High-efficiency red-light emission from polyfluorenes grafted with cyclometalated iridium complexes and charge transport moiety.

    Science.gov (United States)

    Chen, Xiwen; Liao, Jin-Long; Liang, Yongmin; Ahmed, M O; Tseng, Hao-En; Chen, Show-An

    2003-01-22

    We report a new route for the design of electroluminescent polymers by grafting high-efficiency phosphorescent organometallic complexes as dopants and charge transport moieties onto alky side chains of fully conjugated polymers for polymer light-emitting diodes (PLED) with single layer/single polymers. The polymer system studied involves polyfluorene (PF) as the base conjugated polymer, carbazole (Cz) as the charge transport moiety and a source for green emission by forming an electroplex with the PF main chain, and cyclometalated iridium (Ir) complexes as the phosphorescent dopant. Energy transfer from the green Ir complex or an electroplex formed between the fluorene main chain and side-chain carbazole moieties, in addition to that from the PF main chain, to the red Ir complex can significantly enhance the device performance, and a red light-emitting device with the high efficiency 2.8 cd/A at 7 V and 65 cd/m2, comparable to that of the same Ir complex-based OLED, and a broad-band light-emitting device containing blue, green, and red peaks (2.16 cd/A at 9 V) are obtained.

  10. CHAINS-PC, Decay Chain Atomic Densities

    International Nuclear Information System (INIS)

    1994-01-01

    1 - Description of program or function: CHAINS computes the atom density of members of a single radioactive decay chain. The linearity of the Bateman equations allows tracing of interconnecting chains by manually accumulating results from separate calculations of single chains. Re-entrant loops can be treated as extensions of a single chain. Losses from the chain are also tallied. 2 - Method of solution: The Bateman equations are solved analytically using double-precision arithmetic. Poles are avoided by small alterations of the loss terms. Multigroup fluxes, cross sections, and self-shielding factors entered as input are used to compute the effective specific reaction rates. The atom densities are computed at any specified times. 3 - Restrictions on the complexity of the problem: Maxima of 100 energy groups, 100 time values, 50 members in a chain

  11. AN EXPLORATORY APPROACH TO INTEGRATION OF BUSINESS PRACTICES IN SUPPLY CHAIN MANAGEMENT

    Directory of Open Access Journals (Sweden)

    Constangioara Alexandru

    2014-07-01

    After reviewing the literature on supply chain integration, present paper proposes an exploratory analysis of the measurement model corresponding to logistics integration. A Romanian dataset of 21 firms from various industries, covering all levels of a supply chain, from production to commerce is used to conduct a principal factor analysis to test for (a content validity, (b substantive validity, (c uni-dimensionality and (d reliability of scales used to measure integration in supply chains. Also the principal component analysis is used to forecast both dependent and independent variables subsequently used in an OLS estimation of the relationship between supply chain integration and performances in Romanian supply chains. Results support the conclusion that Romanian supply chains focus on a strategy of operational excellence.

  12. Sensitivity analysis on a dose-calculation model for the terrestrial food-chain pathway

    International Nuclear Information System (INIS)

    Abdel-Aal, M.M.

    1994-01-01

    Parameter uncertainty and sensitivity were applied to the U.S. Regulatory Commission's (NRC) Regulatory Guide 1.109 (1977) models for calculating the ingestion dose via a terrestrial food-chain pathway in order to assess the transport of chronically released, low-level effluents from light-water reactors. In the analysis, we used the generation of latin hypercube samples (LHS) and employed a constrained sampling scheme. The generation of these samples is based on information supplied to the LHS program for variables or parameters. The actually sampled values are used to form vectors of variables that are commonly used as inputs to computer models for the purpose of sensitivity and uncertainty analysis. Regulatory models consider the concentrations of radionuclides that are deposited on plant tissues or lead to root uptake of nuclides initially deposited on soil. We also consider concentrations in milk and beef as a consequence of grazing on contaminated pasture or ingestion of contaminated feed by dairy and beef cattle. The radionuclides Sr-90 and Cs-137 were selected for evaluation. The most sensitive input parameters for the model were the ground-dispersion parameter, release rates of radionuclides, and soil-to-plant transfer coefficients of radionuclides. (Author)

  13. Efficient heterologous expression and secretion in Aspergillus oryzae of a llama variable heavy-chain antibody fragment V(HH) against EGFR.

    Science.gov (United States)

    Okazaki, Fumiyoshi; Aoki, Jun-ichi; Tabuchi, Soichiro; Tanaka, Tsutomu; Ogino, Chiaki; Kondo, Akihiko

    2012-10-01

    We have constructed a filamentous fungus Aspergillus oryzae that secretes a llama variable heavy-chain antibody fragment (V(HH)) that binds specifically to epidermal growth factor receptor (EGFR) in a culture medium. A major improvement in yield was achieved by fusing the V(HH) with a Taka-amylase A signal sequence (sTAA) and a segment of 28 amino acids from the N-terminal region of Rhizopus oryzae lipase (N28). The yields of secreted, immunologically active anti-EGFR V(HH) reached 73.8 mg/1 in a Sakaguchi flask. The V(HH) fragments were released from the sTAA or N28 proteins by an indigenous A. oryzae protease during cultivation. The purified recombinant V(HH) fragment was specifically recognized and could bind to the EGFR with a high affinity.

  14. Markov Chain Modelling for Short-Term NDVI Time Series Forecasting

    Directory of Open Access Journals (Sweden)

    Stepčenko Artūrs

    2016-12-01

    Full Text Available In this paper, the NDVI time series forecasting model has been developed based on the use of discrete time, continuous state Markov chain of suitable order. The normalised difference vegetation index (NDVI is an indicator that describes the amount of chlorophyll (the green mass and shows the relative density and health of vegetation; therefore, it is an important variable for vegetation forecasting. A Markov chain is a stochastic process that consists of a state space. This stochastic process undergoes transitions from one state to another in the state space with some probabilities. A Markov chain forecast model is flexible in accommodating various forecast assumptions and structures. The present paper discusses the considerations and techniques in building a Markov chain forecast model at each step. Continuous state Markov chain model is analytically described. Finally, the application of the proposed Markov chain model is illustrated with reference to a set of NDVI time series data.

  15. Force Spectroscopy of Hyaluronan by AFM; From H-bonded Networks Towards Single Chain Behavior

    NARCIS (Netherlands)

    Giannotti, M.I.; Rinaudo, Marguerite; Vancso, Gyula J.

    2007-01-01

    The conformational behavior of hyaluronan (HA) polysaccharide chains in aqueous NaCl solution was characterized directly at the single-molecule level. This comunication reports on one of the first single-chain atomic force microscopy (AFM) experiments performed at variable temperatures,

  16. Isolation and characterization of anti c-met single chain fragment variable (scFv) antibodies.

    Science.gov (United States)

    Qamsari, Elmira Safaie; Sharifzadeh, Zahra; Bagheri, Salman; Riazi-Rad, Farhad; Younesi, Vahid; Abolhassani, Mohsen; Ghaderi, Sepideh Safaei; Baradaran, Behzad; Somi, Mohammad Hossein; Yousefi, Mehdi

    2017-12-01

    The receptor tyrosine kinase (RTK) Met is the cell surface receptor for hepatocyte growth factor (HGF) involved in invasive growth programs during embryogenesis and tumorgenesis. There is compelling evidence suggesting important roles for c-Met in colorectal cancer proliferation, migration, invasion, angiogenesis, and survival. Hence, a molecular inhibitor of an extracellular domain of c-Met receptor that blocks c-Met-cell surface interactions could be of great thera-peutic importance. In an attempt to develop molecular inhibitors of c-Met, single chain variable fragment (scFv) phage display libraries Tomlinson I + J against a specific synthetic oligopeptide from the extracellular domain of c-Met receptor were screened; selected scFv were then characterized using various immune techniques. Three c-Met specific scFv (ES1, ES2, and ES3) were selected following five rounds of panning procedures. The scFv showed specific binding to c-Met receptor, and significantly inhibited proliferation responses of a human colorectal carcinoma cell line (HCT-116). Moreover, anti- apoptotic effects of selected scFv antibodies on the HCT-116 cell line were also evaluated using Annexin V/PI assays. The results demonstrated rates of apoptotic cell death of 46.0, 25.5, and 37.8% among these cells were induced by use of ES1, ES2, and ES3, respectively. The results demonstrated ability to successfully isolate/char-acterize specific c-Met scFv that could ultimately have a great therapeutic potential in immuno-therapies against (colorectal) cancers.

  17. Light in complex dielectrics

    NARCIS (Netherlands)

    Schuurmans, F.J.P.

    1999-01-01

    In this thesis the properties of light in complex dielectrics are described, with the two general topics of "modification of spontaneous emission" and "Anderson localization of light". The first part focuses on the spontaneous emission rate of an excited atom in a dielectric host with variable

  18. Artificial night light alters nocturnal prey interception outcomes for morphologically variable spiders

    Directory of Open Access Journals (Sweden)

    Suet Wai Yuen

    2017-12-01

    Full Text Available Artificial night light has the potential to significantly alter visually-dependent species interactions. However, examples of disruptions of species interactions through changes in light remain rare and how artificial night light may alter predator–prey relationships are particularly understudied. In this study, we examined whether artificial night light could impact prey attraction and interception in Nephila pilipes orb weaver spiders, conspicuous predators who make use of yellow color patterns to mimic floral resources and attract prey to their webs. We measured moth prey attraction and interception responses to treatments where we experimentally manipulated the color/contrast of spider individuals in the field (removed yellow markings and also set up light manipulations. We found that lit webs had lower rates of moth interception than unlit webs. Spider color, however, had no clear impact on moth interception or attraction rates in lit nor unlit webs. The results show that night light can reduce prey interception for spiders. Additionally, this study highlights how environmental and morphological variation can complicate simple predictions of ecological light pollution’s disruption of species interactions.

  19. Artificial night light alters nocturnal prey interception outcomes for morphologically variable spiders.

    Science.gov (United States)

    Yuen, Suet Wai; Bonebrake, Timothy C

    2017-01-01

    Artificial night light has the potential to significantly alter visually-dependent species interactions. However, examples of disruptions of species interactions through changes in light remain rare and how artificial night light may alter predator-prey relationships are particularly understudied. In this study, we examined whether artificial night light could impact prey attraction and interception in Nephila pilipes orb weaver spiders, conspicuous predators who make use of yellow color patterns to mimic floral resources and attract prey to their webs. We measured moth prey attraction and interception responses to treatments where we experimentally manipulated the color/contrast of spider individuals in the field (removed yellow markings) and also set up light manipulations. We found that lit webs had lower rates of moth interception than unlit webs. Spider color, however, had no clear impact on moth interception or attraction rates in lit nor unlit webs. The results show that night light can reduce prey interception for spiders. Additionally, this study highlights how environmental and morphological variation can complicate simple predictions of ecological light pollution's disruption of species interactions.

  20. Dissecting a Light Echo

    Science.gov (United States)

    2008-01-01

    [figure removed for brevity, see original site] Click on image for audio animation This animation illustrates how a light echo works, and how an optical illusion of material moving outward is created. A light echo occurs when a star explodes, acting like a cosmic flashbulb. The light from this explosion zips through nearby dust clumps, illuminating and heating them up slightly. This brief period of warming causes them to glow in infrared, like a chain of Christmas bulbs lighting up one by one. The animation starts by showing the explosion of a star, which results in a flash of light that moves outward in all directions. The direction of our line of sight from Earth is indicated by the blue arrow. When the light flash reaches surrounding dust, shown here as three dark clouds, the dust is heated up, creating infrared light that begins to travel toward Earth (indicated by the red arrows). Dust closest to the explosion lights up first, while the explosion's shock wave takes longer to reach more distant material. This results in light from different parts of the cloud reaching Earth at different times, creating the illusion of motion over time. As the animation shows, the inclination of the cloud toward our line of sight can result in the material seeming to move both away from and toward the central star.

  1. The WFCAM multiwavelength Variable Star Catalog

    Science.gov (United States)

    Ferreira Lopes, C. E.; Dékány, I.; Catelan, M.; Cross, N. J. G.; Angeloni, R.; Leão, I. C.; De Medeiros, J. R.

    2015-01-01

    Context. Stellar variability in the near-infrared (NIR) remains largely unexplored. The exploitation of public science archives with data-mining methods offers a perspective for a time-domain exploration of the NIR sky. Aims: We perform a comprehensive search for stellar variability using the optical-NIR multiband photometric data in the public Calibration Database of the WFCAM Science Archive (WSA), with the aim of contributing to the general census of variable stars and of extending the current scarce inventory of accurate NIR light curves for a number of variable star classes. Methods: Standard data-mining methods were applied to extract and fine-tune time-series data from the WSA. We introduced new variability indices designed for multiband data with correlated sampling, and applied them for preselecting variable star candidates, i.e., light curves that are dominated by correlated variations, from noise-dominated ones. Preselection criteria were established by robust numerical tests for evaluating the response of variability indices to the colored noise characteristic of the data. We performed a period search using the string-length minimization method on an initial catalog of 6551 variable star candidates preselected by variability indices. Further frequency analysis was performed on positive candidates using three additional methods in combination, in order to cope with aliasing. Results: We find 275 periodic variable stars and an additional 44 objects with suspected variability with uncertain periods or apparently aperiodic variation. Only 44 of these objects had been previously known, including 11 RR Lyrae stars on the outskirts of the globular cluster M 3 (NGC 5272). We provide a preliminary classification of the new variable stars that have well-measured light curves, but the variability types of a large number of objects remain ambiguous. We classify most of the new variables as contact binary stars, but we also find several pulsating stars, among which

  2. Orientation of spin-labeled light chain 2 of myosin heads in muscle fibers.

    Science.gov (United States)

    Arata, T

    1990-07-20

    Electron paramagnetic resonance (e.p.r.) spectroscopy has been used to monitor the orientation of spin labels attached rigidly to a reactive SH residue on the light chain 2 (LC2) of myosin heads in muscle fibers. e.p.r. spectra from spin-labeled myosin subfragment-1 (S1), allowed to diffuse into unlabeled rigor (ATP-free) fibers, were roughly approximated by a narrow angular distribution of spin labels centered at 66 degrees relative to the fiber axis, indicating a uniform orientation of S1 bound to actin. On the other hand, spectra from spin-labeled heavy meromyosin (HMM) were roughly approximated by two narrow angular distributions centered at 42 degrees and 66 degrees, suggesting that the LC2 domains of the two HMM heads have different orientations. In contrast to S1 or HMM, the spectra from rigor fibers, in which LC2 of endogenous myosin heads was labeled, showed a random orientation which may be due to distortion imposed by the structure of the filament lattice and the mismatch of the helical periodicities of the thick and thin filaments. However, spectra from the fibers in the presence of ATP analog 5'-adenylyl imidodiphosphate (AMPPNP) were approximated by two narrow angular distributions similar to those obtained with HMM. Thus, AMPPNP may cause the LC2 domain to be less flexible and/or the S2 portion to be more flexible, so as to release the distortion of the LC2 domain and make it return to its natural position. At high ionic strength, AMPPNP disoriented the spin labels as ATP did under relaxing conditions, suggesting that the myosin head is detached from and/or weakly (flexibly) attached to a thin filament.

  3. Variable-angle total internal reflection fluorescence microscopy of intact cells of Arabidopsis thaliana

    Directory of Open Access Journals (Sweden)

    Kim Myung K

    2011-09-01

    Full Text Available Abstract Background Total internal reflection fluorescence microscopy (TIRFM is a powerful tool for observing fluorescently labeled molecules on the plasma membrane surface of animal cells. However, the utility of TIRFM in plant cell studies has been limited by the fact that plants have cell walls, thick peripheral layers surrounding the plasma membrane. Recently, a new technique known as variable-angle epifluorescence microscopy (VAEM was developed to circumvent this problem. However, the lack of a detailed analysis of the optical principles underlying VAEM has limited its applications in plant-cell biology. Results Here, we present theoretical and experimental evidence supporting the use of variable-angle TIRFM in observations of intact plant cells. We show that when total internal reflection occurs at the cell wall/cytosol interface with an appropriate angle of incidence, an evanescent wave field of constant depth is produced inside the cytosol. Results of experimental TIRFM observations of the dynamic behaviors of phototropin 1 (a membrane receptor protein and clathrin light chain (a vesicle coat protein support our theoretical analysis. Conclusions These findings demonstrate that variable-angle TIRFM is appropriate for quantitative live imaging of cells in intact tissues of Arabidopsis thaliana.

  4. A shark antibody heavy chain encoded by a nonsomatically rearranged VDJ is preferentially expressed in early development and is convergent with mammalian IgG.

    Science.gov (United States)

    Rumfelt, L L; Avila, D; Diaz, M; Bartl, S; McKinney, E C; Flajnik, M F

    2001-02-13

    In most vertebrate embryos and neonates studied to date unique antigen receptors (antibodies and T cell receptors) are expressed that possess a limited immune repertoire. We have isolated a subclass of IgM, IgM(1gj), from the nurse shark Ginglymostoma cirratum that is preferentially expressed in neonates. The variable (V) region gene encoding the heavy (H) chain underwent V-D-J rearrangement in germ cells ("germline-joined"). Such H chain V genes were discovered over 10 years ago in sharks but until now were not shown to be expressed at appreciable levels; we find expression of H(1gj) in primary and secondary lymphoid tissues early in life, but in adults only in primary lymphoid tissue, which is identified in this work as the epigonal organ. H(1gj) chain associates covalently with light (L) chains and is most similar in sequence to IgM H chains, but like mammalian IgG has three rather than the four IgM constant domains; deletion of the ancestral IgM C2 domain thus defines both IgG and IgM(1gj). Because sharks are the members of the oldest vertebrate class known to possess antibodies, unique or specialized antibodies expressed early in ontogeny in sharks and other vertebrates were likely present at the inception of the adaptive immune system.

  5. Governance for quality management in tropical food chains

    NARCIS (Netherlands)

    Tilburg, van A.; Trienekens, J.H.; Ruben, R.; Boekel, van M.A.J.S.

    2007-01-01

    This paper provides a framework that focuses on the linkages between several key dimensions of supply chain organisation and performance of perishable tropical food products. The focus is on the relationship between governance regime and quality management, however, two other related variables are

  6. Association between the human herpesvirus 8 and the diffuse nodular lymphoid hyperplasia of the small intestine in common variable immunodeficiency

    International Nuclear Information System (INIS)

    Kokuina, Elena; Dominguez Alvarez, Carlos; Noa Pedroso, Guillermo; Martinez Rodriguez Pedro Ariel

    2009-01-01

    The common variable immunodeficiency (CVID) is the more frequent primary immunodeficiency in clinical field and its presentation forms are very variable. We describe the case of a women presenting with adult CVID with chronic diarrhea syndrome, weight loss and diffuse lymphadenopathies, where the more marked immunologic features were a deep hypogammaglobulinemia of the three major kinds of immunoglobulins and numerical decrease of B cells (CD19 +) and NK cells (CD3 -C D56 +) in peripheral blood. Biopsy of small intestine obtained by video-assisted panendoscope, showed the presence of a multinodular lymphoid hyperplasia with partial atrophy of hairinesses. Immunohistochemistry showed that nodules were high germinal centers with distribution of B cells (CD20 +) and T cells (CD3 +) , similar to that of normal follicle. There was not differential expression of the K and λ light chains. The real time polymerase chain reaction (QRT-PCR) method detected many copies from the genome of type 8 human herpesvirus (VHH-8) (133 copies/μL of DNA) in biopsy of intestinal nodule DNA. VHH-8 infection may to be a significant factor in pathogenesis of lymphoproliferative disorders in patients presenting with CVID

  7. New Variable Stars in the KP2001 Catalog from the Data Base of the Northern Sky Variability Survey

    Science.gov (United States)

    Petrosyan, G. V.

    2018-03-01

    The optical variability of stars in the KP2001 catalog is studied. Monitor data from the automatic Northern Sky Variability Survey (NSVS) are used for this purpose. Of the 257 objects that were studied, 5 are Mira Ceti variables (mirids), 33 are semiregular (SR), and 108 are irregular variables (Ir). The light curves of the other objects show no noticeable signs of variability. For the first time, 11 stars are assigned to the semiregular and 105 stars to the irregular variables. Of the irregular variables, the light curves of two, No. 8 and No. 194, are distinct and are similar to the curves for eclipsing variables. The periods and amplitudes of the mirids and semiregular variables are determined using the "VStar" program package from AAVSO. The absolute stellar magnitudes M K and distances are also estimated, along with the mass loss for the mirids. The behavior of stars from KP2001 in 2MASS and WISE color diagrams is examined.

  8. Azobenzene side-chain liquid crystalline polyesters with outstanding optical storage properties

    DEFF Research Database (Denmark)

    Hvilsted, Søren; Pedersen, M; Holme, NCR

    1998-01-01

    A flexible azobenzene side-chain liquid crystalline (SCLC) polyester architecture employed for reversible optical storage is described. The modular design allows four structural parameters to be individually modified. These parameters: i- the methylene side-chain spacer length, ii- the substituent......,000 are routinely obtained by melt transesterification of the novel diols and selected diacid precursors (parameter iii). Prominent storage features include no prealignment of thin SCLC polyester films prior to the writing process, and sensitivity in a broad laser wavelength window (415-532 nm). Additionally...... sign of fatigue. The non-destructive read out is performed with red light (600-750 nm). Finally, erasing the information can be achieved by heating the polyester film to 80 degrees C or irradiating it briefly with UV-light. In the latter case at least 10,000 write, read and erase cycles are possible...

  9. Molecular immune recognition of botulinum neurotoxin B. The light chain regions that bind human blocking antibodies from toxin-treated cervical dystonia patients. Antigenic structure of the entire BoNT/B molecule.

    Science.gov (United States)

    Atassi, M Zouhair; Jankovic, Joseph; Steward, Lance E; Aoki, K Roger; Dolimbek, Behzod Z

    2012-01-01

    We recently mapped the regions on the heavy (H) chain of botulinum neurotoxin, type B (BoNT/B) recognized by blocking antibodies (Abs) from cervical dystonia (CD) patients who develop immunoresistance during toxin treatment. Since blocking could also be effected by Abs directed against regions on the light (L) chain, we have mapped here the L chain, using the same 30 CD antisera. We synthesized, purified and characterized 32 19-residue L chain peptides that overlapped successively by 5 residues (peptide L32 overlapped with peptide N1 of the H chain by 12 residues). In a given patient, Abs against the L chain seemed less intense than those against H chain. Most sera recognized a limited set of L chain peptides. The levels of Abs against a given region varied with the patient, consistent with immune responses to each epitope being under separate MHC control. The peptides most frequently recognized were: L13, by 30 of 30 antisera (100%); L22, by 23 of 30 (76.67%); L19, by 15 of 30 (50.00%); L26, by 11 of 30 (36.70%); and L14, by 12 of 30 (40.00%). The activity of L14 probably derives from its overlap with L13. The levels of Ab binding decreased in the following order: L13 (residues 169-187), L22 (295-313), L19 (253-271), and L26 (351-369). Peptides L12 (155-173), L18 (239-257), L15 (197-215), L1 (1-19) and L23 (309-327) exhibited very low Ab binding. The remaining peptides had little or no Ab-binding activity. The antigenic regions are analyzed in terms of their three-dimensional locations and the enzyme active site. With the previous localization of the antigenic regions on the BoNT/B H chain, the human Ab recognition of the entire BoNT/B molecule is presented and compared to the recognition of BoNT/A by human blocking Abs. Copyright © 2011. Published by Elsevier GmbH.

  10. Option contracts in fresh produce supply chain with circulation loss

    Directory of Open Access Journals (Sweden)

    Chong Wang

    2013-03-01

    Full Text Available Purpose: The purpose of this paper is to investigate management decisions via option contracts in a two-stage supply chain in which a fresh produce supplier sells to a retailer, considering the circulation loss of the fresh produce. Design/methodology/approach: Authors propose a Stackelberg model to analyze the supply chain members’ decisions in the decentralized supply chain compared with the integrated one under the newsvendor framework. Findings: The results illustrate that there exists a unique optimal option order quantity for the retailer and a unique optimal option order price for the supplier giving certain conditions; furthermore, option contracts cannot coordinate the fresh produce supply chain when the retailer only orders options. Originality/value: Agricultural products especially fresh produce’s characteristics such as circulation loss and high risk are considered. Option contracts and game theory are combined to manage the fresh produce supply chain’s risk. The proposed tool and models are hoped to shed light to the future works in the field of supply chain risk management.

  11. Bullwhip Effect in the Information Flow of a Supply Chain: A Role of Culture

    Directory of Open Access Journals (Sweden)

    Lampret Tadeja

    2014-11-01

    Full Text Available The main goal of our research is to analyze and display causes of a bullwhip effect formation within a supply chain, as well as to provide the appropriate solutions to limit the occurrence of the bullwhip effect by using the proper information flow and partners’ cooperation within the supply chain. The bullwhip effect is one of the most important issues in the supply chain management and it is present in many companies. It preserves a character of invisibility because there are lots of causes for its formation and they are usually difficult to discern. The bullwhip effect is a phenomenon of an increase in the order variability within a supply chain. The higher we are within the supply chain, the higher is the order variability. The company encountered with the whip effect can successfully reduce its impact by improving the information flow, as well as improving partners’ cooperation within the supply chain. In this way the company can limit its negative repercussions and increase the profit. The article focuses on the overview of the bullwhip effect within a distribution chain, from its causes to suggestions and measures how to ease its negative repercussions on the organisation. Part of the causes could be found in the market demand variability and in the lack of communication about the actual marked demand within the supply chain. The rest of the causes are related to obstacles that emerge among different partners within the supply chain (role of culture. A qualitative analysis is applied on the basis of the selected cognitions from the supply chain management. The quantitative analysis is based on the theoretical research of the effective flow of information among the participants and its contribution to the reduction of the bullwhip impact. The article discusses two research questions: 1 The correct information flow within the supply chain and the improvement of the communication among partners can lead to the bullwhip effect reduction

  12. Integration of environmental aspects in modelling and optimisation of water supply chains.

    Science.gov (United States)

    Koleva, Mariya N; Calderón, Andrés J; Zhang, Di; Styan, Craig A; Papageorgiou, Lazaros G

    2018-04-26

    Climate change becomes increasingly more relevant in the context of water systems planning. Tools are necessary to provide the most economic investment option considering the reliability of the infrastructure from technical and environmental perspectives. Accordingly, in this work, an optimisation approach, formulated as a spatially-explicit multi-period Mixed Integer Linear Programming (MILP) model, is proposed for the design of water supply chains at regional and national scales. The optimisation framework encompasses decisions such as installation of new purification plants, capacity expansion, and raw water trading schemes. The objective is to minimise the total cost incurring from capital and operating expenditures. Assessment of available resources for withdrawal is performed based on hydrological balances, governmental rules and sustainable limits. In the light of the increasing importance of reliability of water supply, a second objective, seeking to maximise the reliability of the supply chains, is introduced. The epsilon-constraint method is used as a solution procedure for the multi-objective formulation. Nash bargaining approach is applied to investigate the fair trade-offs between the two objectives and find the Pareto optimality. The models' capability is addressed through a case study based on Australia. The impact of variability in key input parameters is tackled through the implementation of a rigorous global sensitivity analysis (GSA). The findings suggest that variations in water demand can be more disruptive for the water supply chain than scenarios in which rainfalls are reduced. The frameworks can facilitate governmental multi-aspect decision making processes for the adequate and strategic investments of regional water supply infrastructure. Copyright © 2018. Published by Elsevier B.V.

  13. Cavity-Enhanced Raman Spectroscopy for Food Chain Management

    Directory of Open Access Journals (Sweden)

    Vincenz Sandfort

    2018-02-01

    Full Text Available Comprehensive food chain management requires the monitoring of many parameters including temperature, humidity, and multiple gases. The latter is highly challenging because no low-cost technology for the simultaneous chemical analysis of multiple gaseous components currently exists. This contribution proposes the use of cavity enhanced Raman spectroscopy to enable online monitoring of all relevant components using a single laser source. A laboratory scale setup is presented and characterized in detail. Power enhancement of the pump light is achieved in an optical resonator with a Finesse exceeding 2500. A simulation for the light scattering behavior shows the influence of polarization on the spatial distribution of the Raman scattered light. The setup is also used to measure three relevant showcase gases to demonstrate the feasibility of the approach, including carbon dioxide, oxygen and ethene.

  14. Synthesis and characterization of novel side-chain liquid crystalline polycarbonates, 5 - Mesophase characterization of side-chain liquid crystalline polycarbonates with tails of different lengths

    NARCIS (Netherlands)

    Jansen, J.C.; Addink, R.; Nijenhuis, K.T.; Mijs, W.J.

    1999-01-01

    The mesomorphic properties and thermal stability of side-chain LC polycarbonates with alkoxyphenyl benzoate side groups having a short spacer and alkoxy tails ranging from 1 to 8 carbon atoms were studied by DSC, X-ray diffraction and polarized light optical microscopy. All polymers have a smectic A

  15. Unsupervised classification of variable stars

    Science.gov (United States)

    Valenzuela, Lucas; Pichara, Karim

    2018-03-01

    During the past 10 years, a considerable amount of effort has been made to develop algorithms for automatic classification of variable stars. That has been primarily achieved by applying machine learning methods to photometric data sets where objects are represented as light curves. Classifiers require training sets to learn the underlying patterns that allow the separation among classes. Unfortunately, building training sets is an expensive process that demands a lot of human efforts. Every time data come from new surveys; the only available training instances are the ones that have a cross-match with previously labelled objects, consequently generating insufficient training sets compared with the large amounts of unlabelled sources. In this work, we present an algorithm that performs unsupervised classification of variable stars, relying only on the similarity among light curves. We tackle the unsupervised classification problem by proposing an untraditional approach. Instead of trying to match classes of stars with clusters found by a clustering algorithm, we propose a query-based method where astronomers can find groups of variable stars ranked by similarity. We also develop a fast similarity function specific for light curves, based on a novel data structure that allows scaling the search over the entire data set of unlabelled objects. Experiments show that our unsupervised model achieves high accuracy in the classification of different types of variable stars and that the proposed algorithm scales up to massive amounts of light curves.

  16. Creative industries value chain: The value chain logic in supply chain relationships

    OpenAIRE

    Emilia Madudová

    2017-01-01

    The purpose of this paper is to provide a deeper look into value chain logic in supply chain relationships in a creative industries value chains. In recent years, value has been recognized as a key factor in better understanding of consumer behavior and gaining a competitive advantage. In a value chain, added value should be defined at every step of the chain. There should be defined activity which adds value as well as the activity that subtracts any value. The total value can be then calcul...

  17. Multidimensional Structure for Definingthe Effect of Organizational Culture and Supply Chain Culture on Knowledge Sharing in Supply Chain of Automotive Industry: With Emphasis on Improving Supply Chain Performance

    Directory of Open Access Journals (Sweden)

    Mohsen Shafiei Nikabadi

    2012-12-01

    Full Text Available : One of the key aspects of knowledge management is organizational culture. Finding an appropriate culture and key indicators for culture in implementation and execution of knowledge management are one the most important matter in knowledge management implementation in any organization. So, the main purpose of this article was presenting a multidimensional structure for organizational culture and supply chain culture with the aim of effective knowledge sharing in supply chain of automotive industry of Iran. First, according to the literature review, key indicators for any dimension of multidimensional structure of the research were defined. Then, key indicators were revised, adjusted and modified by three industry experts and three college professors, so 4 questions and 5 hypotheses were offered. Next, that multidimensional structure has been assessed as a survey and cause-effect study in supply chains of Iran Khodro Company and Saipa Company.115 industry professionals have participated in this study. In the research, after testing co-linearity between variables, relations between different dimensions of the multidimensional structure have been assessed with the help of path analysis. Research findings showed that the multidimensional structure introduced in the study had an appropriate fitness in automotive industry. The results of path analysis also showed that the culture of the supply chain has had the greatest impact of Business culture. On the other hand, business culture had a strong but indirect effect on supply chain performance. And finally, the greatest effect of knowledge sharing and transferring was on non-financial performance of supply chain.

  18. Dynamically variable spot size laser system

    Science.gov (United States)

    Gradl, Paul R. (Inventor); Hurst, John F. (Inventor); Middleton, James R. (Inventor)

    2012-01-01

    A Dynamically Variable Spot Size (DVSS) laser system for bonding metal components includes an elongated housing containing a light entry aperture coupled to a laser beam transmission cable and a light exit aperture. A plurality of lenses contained within the housing focus a laser beam from the light entry aperture through the light exit aperture. The lenses may be dynamically adjusted to vary the spot size of the laser. A plurality of interoperable safety devices, including a manually depressible interlock switch, an internal proximity sensor, a remotely operated potentiometer, a remotely activated toggle and a power supply interlock, prevent activation of the laser and DVSS laser system if each safety device does not provide a closed circuit. The remotely operated potentiometer also provides continuous variability in laser energy output.

  19. Protein kinase C activation and myosin light chain phosphorylation in 32P-labeled arterial smooth muscle

    International Nuclear Information System (INIS)

    Singer, H.A.

    1990-01-01

    Experiments using 32P-labeled strips of swine carotid artery medial smooth muscle were performed to define the relative contribution of myosin light chain (MLC) phosphorylation as an activation mechanism mediating contractile responses stimulated by phorbol dibutyrate (PDB). Tryptic phosphopeptide mapping of phosphorylated MLC indicated that near-maximal force responses were associated with increases in functional MLC phosphorylation of less than 10% of the total MLC content following tonic (45 min) stimulation by PDB. Significant phosphorylation of MLC residues, consistent with the specificity of protein kinase C, occurred in response to high concentrations of PDB (greater than 0.1 microM). Histamine (10 microM)-induced MLC phosphorylation after 2 min (72.5% of total MLC) or 45 min (61.7%) was restricted to serine residues on peptides thought to contain serine19. Although agonist (histamine)-induced responses were eliminated under conditions of Ca2+ depletion, near-maximal force in response to 10 microM PDB (89.4% of a standard KCl response) was associated with monophosphorylation of less than 9% of the total MLC on peptides interpreted as containing serine19. A substantial fraction of this was localized to threonine residues. The quantitative analysis of the relation between PDB-stimulated force and the residues in MLC phosphorylated supports the concept that PDB stimulation results in activation of arterial smooth muscle cross bridges by MLC-phosphorylation-independent mechanisms

  20. Partial transpose of two disjoint blocks in XY spin chains

    International Nuclear Information System (INIS)

    Coser, Andrea; Tonni, Erik; Calabrese, Pasquale

    2015-01-01

    We consider the partial transpose of the spin reduced density matrix of two disjoint blocks in spin chains admitting a representation in terms of free fermions, such as XY chains. We exploit the solution of the model in terms of Majorana fermions and show that such partial transpose in the spin variables is a linear combination of four Gaussian fermionic operators. This representation allows to explicitly construct and evaluate the integer moments of the partial transpose. We numerically study critical XX and Ising chains and we show that the asymptotic results for large blocks agree with conformal field theory predictions if corrections to the scaling are properly taken into account. (paper)

  1. The Influence of Side-Chain Position on the Optoelectronic Properties of a Red-Emitting Conjugated Polymer

    NARCIS (Netherlands)

    Lu, Li Ping; Finlayson, Chris E.; Kabra, Dinesh; Albert-Seifried, Sebastian; Song, Myoung Hoon; Havenith, Remco W. A.; Tu, Guoli; Huck, Wilhelm T. S.; Friend, Richard H.

    2013-01-01

    A study of the organic semiconductor F8TBT is presented, directly comparing a conventional form (F8TBT-out) with a form with varied alkyl side-chain position (F8TBT-in), in terms of optical properties and device performance in light-emitting-diodes (LEDs). Computational simulations of the side-chain

  2. [Survival strategy of photosynthetic organisms. 1. Variability of the extent of light-harvesting pigment aggregation as a structural factor optimizing the function of oligomeric photosynthetic antenna. Model calculations].

    Science.gov (United States)

    Fetisova, Z G

    2004-01-01

    In accordance with our concept of rigorous optimization of photosynthetic machinery by a functional criterion, this series of papers continues purposeful search in natural photosynthetic units (PSU) for the basic principles of their organization that we predicted theoretically for optimal model light-harvesting systems. This approach allowed us to determine the basic principles for the organization of a PSU of any fixed size. This series of papers deals with the problem of structural optimization of light-harvesting antenna of variable size controlled in vivo by the light intensity during the growth of organisms, which accentuates the problem of antenna structure optimization because optimization requirements become more stringent as the PSU increases in size. In this work, using mathematical modeling for the functioning of natural PSUs, we have shown that the aggregation of pigments of model light-harvesting antenna, being one of universal optimizing factors, furthermore allows controlling the antenna efficiency if the extent of pigment aggregation is a variable parameter. In this case, the efficiency of antenna increases with the size of the elementary antenna aggregate, thus ensuring the high efficiency of the PSU irrespective of its size; i.e., variation in the extent of pigment aggregation controlled by the size of light-harvesting antenna is biologically expedient.

  3. Effects of weather conditions, light conditions, and road lighting on vehicle speed.

    Science.gov (United States)

    Jägerbrand, Annika K; Sjöbergh, Jonas

    2016-01-01

    Light conditions are known to affect the number of vehicle accidents and fatalities but the relationship between light conditions and vehicle speed is not fully understood. This study examined whether vehicle speed on roads is higher in daylight and under road lighting than in darkness, and determined the combined effects of light conditions, posted speed limit and weather conditions on driving speed. The vehicle speed of passenger cars in different light conditions (daylight, twilight, darkness, artificial light) and different weather conditions (clear weather, rain, snow) was determined using traffic and weather data collected on an hourly basis for approximately 2 years (1 September 2012-31 May 2014) at 25 locations in Sweden (17 with road lighting and eight without). In total, the data included almost 60 million vehicle passes. The data were cleaned by removing June, July, and August, which have different traffic patterns than the rest of the year. Only data from the periods 10:00 A.M.-04:00 P.M. and 06:00 P.M.-10:00 P.M. were used, to remove traffic during rush hour and at night. Multivariate adaptive regression splines was used to evaluate the overall influence of independent variables on vehicle speed and nonparametric statistical testing was applied to test for speed differences between dark-daylight, dark-twilight, and twilight-daylight, on roads with and without road lighting. The results show that vehicle speed in general depends on several independent variables. Analyses of vehicle speed and speed differences between daylight, twilight and darkness, with and without road lighting, did not reveal any differences attributable to light conditions. However, vehicle speed decreased due to rain or snow and the decrease was higher on roads without road lighting than on roads with lighting. These results suggest that the strong association between traffic accidents and darkness or low light conditions could be explained by drivers failing to adjust their

  4. The Analysis of Orders of Perishable Goods in Relation to the Bullwhip Effect in the Logistic Supply Chain of the Food Industry: a Case Study

    Science.gov (United States)

    Chocholáč, Jan; Průša, Petr

    2016-12-01

    The bullwhip effect generally refers to the phenomenon where order variability increases as the orders move upstream in the supply chain. It is serious problem for every member of the supply chain. This effect begins at customers and passes through the chain to producers, which are at the end of the logistic chain. Especially food supply chains are affected by this issue. These chains are unique for problems of expiration of goods (particularly perishable goods), variable demand, orders with quantity discounts and effort to maximize the customer satisfaction. This paper will present the problem of the bullwhip effect in the real supply chain in the food industry. This supply chain consists of approximately 350 stores, four central warehouses and more than 1000 suppliers, but the case study will examine 87 stores, one central warehouse and one supplier in 2015. The aim of this paper is the analysis of the order variability between the various links in this chain and confirmation of the bullwhip effect in this chain. The subject of the analysis will be perishable goods.

  5. Fourier analysis of the light curves of eclipsing variables. XI

    International Nuclear Information System (INIS)

    Kopal, Z.

    1977-01-01

    The aim of the present paper is to introduce a new definition of the loss of light suffered by mutual eclipses of the components of close binary systems: namely, as a cross-correlation of two apertures representing the eclipsing and eclipsed discs. The advantages of such a strategy over the more conventional (geometrical) approach are (a) greater symmetry of the respective expressions; (b) greater affinity of expressions arising from distortion with those expressing the light changes due to eclipses of spherical stars; and (c) greater freedom in dealing with the effects of particular distribution of brightness over the disc of the star undergoing eclipse (generalized limb-darkening), as well as of possible semi-transparency of the eclipsing component (Wolf-Rayet stars). In point of fact, none of these tasks could be handled with equal ease by any other technique; nor could the corresponding loss of light be so automated by any other approach. (Auth.)

  6. A novel option for reducing free light chains in myeloma kidney: supra-hemodiafiltration with endogenous reinfusion (HFR).

    Science.gov (United States)

    Pasquali, Sonia; Iannuzzella, Francesco; Corradini, Mattia; Mattei, Silvia; Bovino, Achiropita; Stefani, Alfredo; Palladino, Giuseppe; Caiazzo, Marialuisa

    2015-04-01

    In myeloma cast nephropathy, fast reduction of serum free light chain (FLC) levels correlates with renal recovery. Recently, extracorporeal treatments using filters with a high-molecular weight cut-off have been successfully used for FLC removal. However, using these new filters, high cost and elevated albumin leakage are common drawbacks. We studied a new and cheaper therapeutic approach with adsorbent resins to evaluate its efficacy. We treated four patients, affected by dialysis-dependent acute kidney injury (AKI) due to biopsy proven de novo FLC myeloma cast nephropathy. Each patient underwent bortezomib chemotherapy and extracorporeal treatment with the supra-hemodiafiltration with endogenous reinfusion (HFR) technique (Supra-HFR, Bellco Mirandola, Modena, Italy). Supra-HFR is a kind of hemodiafiltration that utilizes separated convection, diffusion and adsorption. The sorbent cartridge has a high affinity for FLC (both κ and λ) but is able to re-infuse albumin, avoiding the need for albumin perfusions. Supra HFR treatments (4 h each) were carried out for eight consecutive days and then every other day. All patients showed a significant reduction of serum FLC, whereas serum albumin concentration remained unchanged. Renal function recovered in three out of four patients. FLC removal with adsorbent resins represents an effective therapeutic strategy that does not require replacement with albumin .

  7. Auto-SCT improves survival in systemic light chain amyloidosis: a retrospective analysis with 14-year follow-up.

    Science.gov (United States)

    Parmar, S; Kongtim, P; Champlin, R; Dinh, Y; Elgharably, Y; Wang, M; Bashir, Q; Shah, J J; Shah, N; Popat, U; Giralt, S A; Orlowski, R Z; Qazilbash, M H

    2014-08-01

    Optimal treatment approach continues to remain a challenge for systemic light chain amyloidosis (AL). So far, Auto-SCT is the only modality associated with long-term survival. However, failure to show survival benefit in randomized study raises questions regarding its efficacy. We present a comparative outcome analysis of Auto-SCT to conventional therapies (CTR) in AL patients treated over a 14-year period at our institution. Out of the 145 AL amyloidosis patients, Auto-SCT was performed in 80 patients with 1-year non-relapse mortality rate of 12.5%. Novel agents were used as part of induction therapy in 56% of transplant recipients vs 46% of CTR patients. Hematological and organ responses were seen in 74.6% and 39% in the Auto-SCT arm vs 53% and 12% in the CTR arm, respectively. The projected 5-year survival for Auto-SCT vs CTR was 63% vs 38%, respectively. Landmark analysis of patients alive at 1-year after diagnosis showed improved 5-year OS of 72% with Auto-SCT vs 65% in the CTR arm. In the multivariate analysis, age SCT were associated with improved survival. In conclusion, Auto-SCT is associated with long-term survival for patients with AL amyloidosis.

  8. Acoustic Design of Super-light Structures

    DEFF Research Database (Denmark)

    Christensen, Jacob Ellehauge; Hertz, Kristian Dahl; Brunskog, Jonas

    in a controlled laboratory environment have been conducted with the element in order to evaluate its performance in airborne and impact sound insulation. These results have been employed in simulations of the flanking transmission to estimate the in-situ performance of the super-light slab element. The flanking...... aggregate (leca) along with a newly developed technology called pearl-chain reinforcement, which is a system for post-tensioning. Here, it is shown how to combine these technologies within a precast super-light slab element, while honoring the requirements of a holistic design. Acoustic experiments...

  9. Human heavy-chain variable region gene family nonrandomly rearranged in familial chronic lymphocytic leukemia

    International Nuclear Information System (INIS)

    Shen, A.; Humphries, C.; Tucker, P.; Blattner, F.

    1987-01-01

    The authors have identified a family of human immunoglobulin heavy-chain variable-region (V/sub H/) genes, one member of which is rearranged in two affected members of a family in which the father and four of five siblings developed chronic lymphocytic leukemia. Cloning and sequencing of the rearranged V/sub H/ genes from leukemic lymphocytes of three affected siblings showed that two siblings had rearranged V/sub H/ genes (V/sub H/TS1 and V/sub H/WS1) that were 90% homologous. The corresponding germ-line gene, V/sub H/251, was found to part of a small (four gene) V/sub H/ gene family, which they term V/sub H/V. The DNA sequence homology to V/sub H/WS1 (95%) and V/sub H/TS1 (88%) and identical restriction sites on the 5' side of V/sub H/ confirm that rearrangement of V/sub H/251 followed by somatic mutation produced the identical V/sub H/ gene rearrangements in the two siblings. V/sub H/TS1 is not a functional V/sub H/ gene; a functional V/sub H/ rearrangement was found on the other chromosome of this patient. The other two siblings had different V/sub H/ gene rearrangements. All used different diversity genes. Mechanisms proposed for nonrandom selection of a single V/sub H/ gene include developmental regulation of this V/sub H/ gene rearrangement or selection of a subpopulation of B cells in which this V/sub H/ has been rearranged

  10. Temporal Variability of Canopy Light Use Efficiency and its Environmental Controls in a Subtropical Mangrove Wetland

    Science.gov (United States)

    Zhu, X.

    2016-12-01

    Mangrove wetlands play an important role in global carbon cycle due to their strong carbon sequestration resulting from high plant carbon assimilation and low soil respiration. However, temporal variability of carbon sequestration in mangrove wetlands is less understood since carbon processes of mangrove wetlands are influenced by many complicated and concurrent environmental controls including tidal activities, site climate and soil conditions. Canopy light use efficiency (LUE), is the most important plant physiological parameter that can be used to describe the temporal dynamics of canopy photosynthesis, and therefore a better characterization of temporal variability of canopy LUE will improve our understanding in mangrove photosynthesis and carbon balance. One of our aims is to study the temporal variability of canopy LUE and its environmental controls in a subtropical mangrove wetland. Half-hourly canopy LUE is derived from eddy covariance (EC) carbon flux and photosynthesis active radiation observations, and half-hourly environmental controls we measure include temperature, humidity, precipitation, radiation, tidal height, salinity, etc. Another aim is to explore the links between canopy LUE and spectral indices derived from near-surface tower-based remote sensing (normalized difference vegetation index, enhanced vegetation index, photochemical reflectance index, solar-induced chlorophyll fluorescence, etc.), and then identify potential quantitative relationships for developing remote sensing-based estimation methods of canopy LUE. At present, some instruments in our in-situ observation system have not yet been installed (planned in next months) and therefore we don't have enough measurements to support our analysis. However, a preliminary analysis of our historical EC and climate observations in past several years indicates that canopy LUE shows strong temporal variability and is greatly affected by environmental factors such as tidal activity. Detailed and

  11. Amazon forest structure generates diurnal and seasonal variability in light utilization

    Science.gov (United States)

    Douglas C. Morton; Jeremy Rubio; Bruce D. Cook; Jean-Philippe Gastellu-Etchegorry; Marcos Longo; Hyeungu Choi; Maria Hunter; Michael Keller

    2016-01-01

    The complex three-dimensional (3-D) structure of tropical forests generates a diversity of light environments for canopy and understory trees. Understanding diurnal and seasonal changes in light availability is critical for interpreting measurements of net ecosystem exchange and improving ecosystem models. Here, we used the Discrete Anisotropic Radiative Transfer (DART...

  12. Supply chain challenges. building relationships.

    Science.gov (United States)

    Beth, Scott; Burt, David N; Copacino, William; Gopal, Chris; Lee, Hau L; Lynch, Robert Porter; Morris, Sandra

    2003-07-01

    Supply chain management is all about software and systems, right? Put in the best technology, sit back, and watch as your processes run smoothly and the savings roll in? Apparently not. When HBR convened a panel of leading thinkers in the field of supply chain management, technology was not top of mind. People and relationships were the dominant issues of the day. The opportunities and problems created by globalization, for example, are requiring companies to establish relationships with new types of suppliers. The ever-present pressure for speed and cost containment is making it even more important to break down stubbornly high internal barriers and establish more effective cross-functional relationships. The costs of failure have never been higher. The leading supply chain performers are applying new technology, new innovations, and process thinking to far greater advantage than the laggards, reaping tremendous gains in all the variables that affect shareholder value: cost, customer service, asset productivity, and revenue generation. And the gap between the leaders and the losers is growing in almost every industry. This roundtable gathered many of the leading thinkers and doers in the field of supply chain management, including practitioners Scott Beth of Intuit, Sandra Morris of Intel, and Chris Gopal of Unisys. David Burt of the University of San Diego and Stanford's Hau Lee bring the latest research from academia. Accenture's William Copacino and the Warren Company's Robert Porter Lynch offer the consultant's perspectives. Together, they take a wide-ranging view of such topics as developing talent, the role of the chief executive, and the latest technologies, exploring both the tactical and the strategic in the current state of supply chain management.

  13. Standard handbook of chains chains for power transmission and material handling

    CERN Document Server

    2005-01-01

    A BRIEF HISTORY OF THE DEVELOPMENT OF CHAINEarly DevelopmentsCog ChainCast Detachable ChainCast Pintle ChainPrecision Roller ChainEngineering Steel ChainSilent ChainFlat-Top ChainTerminologyA CHAIN OVERVIEW: USES AND ADVANTAGESGeneralTypes of ChainScope of Chains CoveredStyles and Forms of ChainsStraight and Offset Link ChainsChains With and Without RollersUses of ChainStandard Chains and Their UsesThe Advantages of Chains in ApplicationsAdvantages of Roller Chains in DrivesAdvantages of Silent Chain Drives

  14. The effects of light-emitting diode lighting on greenhouse plant growth and quality

    Directory of Open Access Journals (Sweden)

    Margit Olle

    2013-06-01

    Full Text Available The aim of this study is to present the light emitting diode (LED technology for greenhouse plant lighting and to give an overview about LED light effects on photosynthetic indices, growth, yield and nutritional value in green vegetables and tomato, cucumber, sweet pepper transplants. The sole LED lighting, applied in closed growth chambers, as well as combinations of LED wavelengths with conventional light sources, fluorescent and high pressure sodium lamp light, and natural illumination in greenhouses are overviewed. Red and blue light are basal in the lighting spectra for green vegetables and tomato, cucumber, and pepper transplants; far red light, important for photomorphogenetic processes in plants also results in growth promotion. However, theoretically unprofitable spectral parts as green or yellow also have significant physiological effects on investigated plants. Presented results disclose the variability of light spectral effects on different plant species and different physiological indices.

  15. Prognosis of Light Chain Amyloidosis With Preserved LVEF: Added Value of 2D Speckle-Tracking Echocardiography to the Current Prognostic Staging System.

    Science.gov (United States)

    Barros-Gomes, Sergio; Williams, Brittney; Nhola, Lara F; Grogan, Martha; Maalouf, Joseph F; Dispenzieri, Angela; Pellikka, Patricia A; Villarraga, Hector R

    2017-04-01

    This study evaluated whether 2-dimensional speckle-tracking echocardiography (2D-STE) has incremental value for prognosis over traditional clinical, echocardiographic, and serological markers-with main focus on the current prognostic staging system-in light-chain (AL) amyloidosis patients with preserved left ventricular ejection fraction. Cardiac amyloidosis (CA) is the major determinant of outcome in AL amyloidosis. The current prognostic staging system is based primarily on serum levels of cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and free light chain differential (FLC-diff). Consecutive patients with biopsy-proven AL amyloidosis and left ventricular ejection fraction ≥55% were divided into group 1 with CA (n = 63) and group 2 without CA (n = 87). Global longitudinal strain (GLS) by 2D-STE was performed with Vivid E9 (GE Healthcare Co., Milwaukee, Wisconsin) and syngo Velocity Vector Imaging (VVI) software (Siemens Medical Solutions USA, Inc., Malvern, Pennsylvania) (GLS GE and GLS VVI , respectively). Thirty-two deaths (51%) occurred in group 1 and 13 (15%) in group 2 (p ≤ 0.001). Group 1 had thicker walls, lower early diastolic tissue Doppler velocity at septal mitral annulus, and greater left ventricular mass, left atrial volume, glomerular filtration rate, FLC-diff, cTnT, and NT-proBNP (p value over cTnT, NT-proBNP, and FLC-diff. For survival analysis limited to group 2 (non-CA), GLS GE and GLS VVI both predicted all-cause mortality (GLS GE HR: 1.23; 95% CI: 1.03 to 1.47 [p = 0.02]; GLS VVI HR: 1.22; 95% CI: 1.01 to 1.49 [p = 0.04], respectively). 2D-STE predicted outcome and provided incremental prognostic information over the current prognostic staging system, especially in the group without CA. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. Cutting Food Waste through Cooperation along the Food Supply Chain

    Directory of Open Access Journals (Sweden)

    Christine Göbel

    2015-01-01

    Full Text Available Food produced but not used for human consumption is a waste of natural resources. In order to prevent and reduce food waste, the main causes have to be identified systematically along the food supply chain (FSC. The aim of this study is (1 to shed light on the causes and effects of food waste through the analysis of 44 qualitative expert interviews examining the processes and intermediaries along the German food chain and (2 to find methods to reduce it. Results indicate that food waste occurs at all stages in the food chain. Thus, there is no single culprit to be blamed. Besides, the identified reasons for food waste differ between product groups; not a single solution can cause notable change. Furthermore, the analysis demonstrates that the causes and effects of food waste are to be found at different stages of the value chain. Hence, it is of high importance to improve communication and to raise a new appreciation for food among all stakeholders of the food supply chain in order to develop a more sustainable food system. Information on the topic of food waste needs to be shared among all actors of the supply chain. They need to share responsibility and work together to reduce food waste.

  17. Crystal structure of the anti-(carcinoembryonic antigen) single-chain Fv antibody MFE-23 and a model for antigen binding based on intermolecular contacts.

    Science.gov (United States)

    Boehm, M K; Corper, A L; Wan, T; Sohi, M K; Sutton, B J; Thornton, J D; Keep, P A; Chester, K A; Begent, R H; Perkins, S J

    2000-03-01

    MFE-23 is the first single-chain Fv antibody molecule to be used in patients and is used to target colorectal cancer through its high affinity for carcinoembryonic antigen (CEA), a cell-surface member of the immunoglobulin superfamily. MFE-23 contains an N-terminal variable heavy-chain domain joined by a (Gly(4)Ser)(3) linker to a variable light-chain (V(L)) domain (kappa chain) with an 11-residue C-terminal Myc-tag. Its crystal structure was determined at 2.4 A resolution by molecular replacement with an R(cryst) of 19.0%. Five of the six antigen-binding loops, L1, L2, L3, H1 and H2, conformed to known canonical structures. The sixth loop, H3, displayed a unique structure, with a beta-hairpin loop and a bifurcated apex characterized by a buried Thr residue. In the crystal lattice, two MFE-23 molecules were associated back-to-back in a manner not seen before. The antigen-binding site displayed a large acidic region located mainly within the H2 loop and a large hydrophobic region within the H3 loop. Even though this structure is unliganded within the crystal, there is an unusually large region of contact between the H1, H2 and H3 loops and the beta-sheet of the V(L) domain of an adjacent molecule (strands DEBA) as a result of intermolecular packing. These interactions exhibited remarkably high surface and electrostatic complementarity. Of seven MFE-23 residues predicted to make contact with antigen, five participated in these lattice contacts, and this model for antigen binding is consistent with previously reported site-specific mutagenesis of MFE-23 and its effect on CEA binding.

  18. Clinical usefulness of serum free light chains measurement in patients with multiple myeloma: comparative analysis of two different tests

    Directory of Open Access Journals (Sweden)

    Tadeusz Kubicki

    2017-01-01

    Full Text Available Introduction: There are two commercially available tests for measurement of serum free light chains (sFLC in multiple myeloma (MM patients – Freelite and N Latex FLC. The aim of this study was to perform an assessment and direct comparison of the usefulness of the methods in routine clinical practice.Methods: 40 refractory/relapsed MM patients underwent routine disease activity assessment studies, along with sFLC analysis using both assays. Correlation and concordance between the tests and sensitivity of studied methods of sFLC assessment were established. Special attention was focused on sFLC results in patients finally evaluated after completing the treatment. Results: A weak correlation for the measurement of both κ [Passing–Bablok slope (PB = 0.7681] and λ chains [(PB = 1.542] was found. Using Bland–Altman plots, a bias of 0.0467 (κ and -0.2133 (λ between the measurements was documented. The concordance coefficient equaled 0.87 for κ, 0.62 for λ and 0.52 for κ/λ ratio. Ten patients had an abnormal Freelite assay κ/λ ratio and normal N Latex FLC κ/λ ratio. Three of these patients had negative serum protein electrophoresis results and fulfilled diagnostic criteria of stringent complete remission (sCR according to N Latex FLC (but not according to Freelite. When the κ/λ ratio obtained by both methods was compared to patients’ serum/urine protein electrophoresis and immunofixation results, sensitivity of Freelite and N Latex FLC was established to be 62.5% and 41%, respectively. Conclusions: There was no strong correlation or concordance between the two assays, and the sensitivity in terms of sFLC detection was different. This may cause problems when diagnosis of sCR is considered.

  19. Fast response dry-type artificial molecular muscles with [c2]daisy chains

    Science.gov (United States)

    Iwaso, Kazuhisa; Takashima, Yoshinori; Harada, Akira

    2016-06-01

    Hierarchically organized myosin and actin filaments found in biological systems exhibit contraction and expansion behaviours that produce work and force by consuming chemical energy. Inspired by these naturally occurring examples, we have developed photoresponsive wet- and dry-type molecular actuators built from rotaxane-based compounds known as [c2]daisy chains (specifically, [c2]AzoCD2 hydrogel and [c2]AzoCD2 xerogel). These actuators were prepared via polycondensation between four-armed poly(ethylene glycol) and a [c2]daisy chain based on α-cyclodextrin as the host component and azobenzene as a photoresponsive guest component. The light-induced actuation arises from the sliding motion of the [c2]daisy chain unit. Ultraviolet irradiation caused the gels to bend towards the light source. The response of the [c2]AzoCD2 xerogel, even under dry conditions, is very fast (7° every second), which is 10,800 times faster than the [c2]AzoCD2 hydrogel (7° every 3 h). In addition, the [c2]AzoCD2 xerogel was used as a crane arm to lift an object using ultraviolet irradiation to produce mechanical work.

  20. Automated Blazar Light Curves Using Machine Learning

    Energy Technology Data Exchange (ETDEWEB)

    Johnson, Spencer James [Los Alamos National Lab. (LANL), Los Alamos, NM (United States)

    2017-07-27

    This presentation describes a problem and methodology pertaining to automated blazar light curves. Namely, optical variability patterns for blazars require the construction of light curves and in order to generate the light curves, data must be filtered before processing to ensure quality.

  1. The Impact of Knowledge Management Capability, Organizational Learning, and Supply Chain Management Practices on Organizational Performance

    Directory of Open Access Journals (Sweden)

    Ingy Essam Eldin Salama

    2017-03-01

    Full Text Available The focus of this research is developing and examining a conceptual framework relating resource-based organizational capabilities and inter-organizational practices with organizational performance. Specifically, it investigates the relationship between knowledge management capability, organizational learning, supply chain management practices and organizational performance. Such a study is important as it contributes to the growing body of literature that links organizational capabilities and practices with organizational performance. In addition, it also contributes to empirical knowledge by applying the proposed conceptual framework in the Egyptian context, which is currently under-researched. The research approach adopted in this research includes empirical examination of the hypothesized relationships among research variables applied on 63 factories with more than 100 employees located at New Borg Al-Arab industrial city using self-administrated questionnaires. The findings of this research provide evidence that knowledge management capability has an impact on organizational learning as well as on supply chain management practices. However, none of the research variables; i.e. knowledge management capability, organizational learning and supply chain management practices have an impact on organizational performance. The main conclusion drawn from this study is that knowledge management capability may be useful to managers for predicting organizational learning and coordinating supply chain management practices between supply chain members. In addition, it could be concluded that organizational performance, in the factories under study, is affected by variables other than knowledge management capability, organizational learning and supply chain management practices.

  2. Detection of clonal immunoglobulin heavy chain gene rearrangements by the polymerase chain reaction and capillary gel electrophoresis.

    Science.gov (United States)

    Fan, Hongxin; Robetorye, Ryan S

    2013-01-01

    Although well-established diagnostic criteria exist for mature B-cell neoplasms, a definitive diagnosis of a B-cell lymphoproliferative disorder cannot always be obtained using more conventional techniques such as flow cytometric immunophenotyping, conventional cytogenetics, fluorescence in situ hybridization, or immunohistochemistry. However, because B-cell malignancies contain identically rearranged immunoglobulin heavy chain genes, the polymerase chain reaction (PCR) can be a fast, convenient, and dependable option to identify clonal B-cell processes. This chapter describes the use of PCR and capillary electrophoresis to identify clonal immunoglobulin heavy chain (IGH) variable and joining region (VH-JH) gene rearrangements (IGH VH-JH PCR) using a commercially available method employing multiple multiplex PCR tubes that was originally developed as the result of a large European BIOMED-2 collaborative study (Invivoscribe Technologies). The core protocol involves the use of three separate master mix tubes that target the conserved framework (FR1, FR2, and FR3) and joining (J) regions of the IGH gene. Analysis of these three framework regions can detect approximately 88% of clonal IGH gene rearrangements.

  3. Annual variability in light absorption by particles and colored dissolved organic matter in the Crimean coastal waters (the Black Sea)

    Science.gov (United States)

    Churilova, T.; Moiseeva, N.; Efimova, T.; Suslin, V.; Krivenko, O.; Zemlianskaia, E.

    2017-11-01

    Bio-optical studies were carried out in coastal waters around the Crimea peninsula in different seasons 2016. It was shown that variability of chlorophyll a concentration (Chl-a), light absorption by suspended particles (ap(λ)), phytoplankton pigments (aph(λ)), non-algal particles (aNAP(λ)) and by colored dissolved organic matter (aCDOM(λ)) in the Crimea coastal water was high ( order of magnitudes) in all seasons 2016. Relationships between ap(440), aph(440) and Chl-a were obtained and their seasonal differences were analyzed. Spectral distribution of aNAP(λ) and aCDOM(λ) were parameterized. Seasonality in aCDOM(λ) parameterization was revealed, but - in aNAP(λ) parameterization was not revealed. The budget of light absorption by aph(λ), aNAP(λ) i aCDOM(λ) at 440 nm was assessed and its seasonal dynamics was analyzed.

  4. BLAM (Benthic Light Availability Model): A Proposed Model of Hydrogeomorphic Controls on Light in Rivers

    Science.gov (United States)

    Julian, J. P.; Doyle, M. W.; Stanley, E. H.

    2006-12-01

    Light is vital to the dynamics of aquatic ecosystems. It drives photosynthesis and photochemical reactions, affects thermal structure, and influences behavior of aquatic biota. Despite the fundamental role of light to riverine ecosystems, light studies in rivers have been mostly neglected because i) boundary conditions (e.g., banks, riparian vegetation) make ambient light measurements difficult, and ii) the optical water quality of rivers is highly variable and difficult to characterize. We propose a benthic light availability model (BLAM) that predicts the percent of incoming photosynthetically active radiation (PAR) available at the river bed. BLAM was developed by quantifying light attenuation of the five hydrogeomorphic controls that dictate riverine light availability: topography, riparian vegetation, channel geometry, optical water quality, and water depth. BLAM was calibrated using hydrogeomorphic data and light measurements from two rivers: Deep River - a 5th-order, turbid river in central North Carolina, and Big Spring Creek - a 2nd-order, optically clear stream in central Wisconsin. We used a series of four PAR sensors to measure i) above-canopy PAR, ii) PAR above water surface, iii) PAR below water surface, and iv) PAR on stream bed. These measurements were used to develop empirical light attenuation coefficients, which were then used in combination with optical water quality measurements, shading analyses, channel surveys, and flow records to quantify the spatial and temporal variability in riverine light availability. Finally, we apply BLAM to the Baraboo River - a 6th-order, 120-mile, unimpounded river in central Wisconsin - in order to characterize light availability along the river continuum (from headwaters to mouth).

  5. Cardiac Light Chain Amyloidosis: The Role of Metal Ions in Oxidative Stress and Mitochondrial Damage.

    Science.gov (United States)

    Diomede, Luisa; Romeo, Margherita; Rognoni, Paola; Beeg, Marten; Foray, Claudia; Ghibaudi, Elena; Palladini, Giovanni; Cherny, Robert A; Verga, Laura; Capello, Gian Luca; Perfetti, Vittorio; Fiordaliso, Fabio; Merlini, Giampaolo; Salmona, Mario

    2017-09-20

    The knowledge of the mechanism underlying the cardiac damage in immunoglobulin light chain (LC) amyloidosis (AL) is essential to develop novel therapies and improve patients' outcome. Although an active role of reactive oxygen species (ROS) in LC-induced cardiotoxicity has already been envisaged, the actual mechanisms behind their generation remain elusive. This study was aimed at further dissecting the action of ROS generated by cardiotoxic LC in vivo and investigating whether transition metal ions are involved in this process. In the absence of reliable vertebrate model of AL, we used the nematode Caenorhabditis elegans, whose pharynx is an "ancestral heart." LC purified from patients with severe cardiac involvement intrinsically generated high levels of ROS and when administered to C. elegans induced ROS production, activation of the DAF-16/forkhead transcription factor (FOXO) pathway, and expression of proteins involved in stress resistance and survival. Profound functional and structural ROS-mediated mitochondrial damage, similar to that observed in amyloid-affected hearts from AL patients, was observed. All these effects were entirely dependent on the presence of metal ions since addition of metal chelator or metal-binding 8-hydroxyquinoline compounds (chelex, PBT2, and clioquinol) permanently blocked the ROS production and prevented the cardiotoxic effects of amyloid LC. Innovation and Conclusion: Our findings identify the key role of metal ions in driving the ROS-mediated toxic effects of LC. This is a novel conceptual advance that paves the way for new pharmacological strategies aimed at not only counteracting but also totally inhibiting the vicious cycle of redox damage. Antioxid. Redox Signal. 27, 567-582.

  6. Extreme event statistics in a drifting Markov chain

    Science.gov (United States)

    Kindermann, Farina; Hohmann, Michael; Lausch, Tobias; Mayer, Daniel; Schmidt, Felix; Widera, Artur

    2017-07-01

    We analyze extreme event statistics of experimentally realized Markov chains with various drifts. Our Markov chains are individual trajectories of a single atom diffusing in a one-dimensional periodic potential. Based on more than 500 individual atomic traces we verify the applicability of the Sparre Andersen theorem to our system despite the presence of a drift. We present detailed analysis of four different rare-event statistics for our system: the distributions of extreme values, of record values, of extreme value occurrence in the chain, and of the number of records in the chain. We observe that, for our data, the shape of the extreme event distributions is dominated by the underlying exponential distance distribution extracted from the atomic traces. Furthermore, we find that even small drifts influence the statistics of extreme events and record values, which is supported by numerical simulations, and we identify cases in which the drift can be determined without information about the underlying random variable distributions. Our results facilitate the use of extreme event statistics as a signal for small drifts in correlated trajectories.

  7. Development Value Chains meet Business Supply Chains : The concept of Global Value Chains unraveled

    NARCIS (Netherlands)

    S. Drost (Sarah); J.C.A.C. van Wijk (Jeroen); S.R. Vellema (Sietze)

    2011-01-01

    textabstractValue chain promotion is considered a key element of private sector development strategies and pro-poor growth. However, (value) chain concepts are rather complex and unclear. This paper unravels the concept of global value chains and studies the diversity of key value chain-related

  8. Response to variable light intensity in photoacclimated algae and cyanobacteria exposed to atrazine

    Energy Technology Data Exchange (ETDEWEB)

    Deblois, Charles P.; Dufresne, Karine [Department of Biological Sciences-TOXEN, Ecotoxicology of Aquatic Microorganisms Laboratory, Universite du Quebec a Montreal, Succ. Centre-Ville, Montreal, Quebec (Canada); Juneau, Philippe, E-mail: juneau.philippe@uqam.ca [Department of Biological Sciences-TOXEN, Ecotoxicology of Aquatic Microorganisms Laboratory, Universite du Quebec a Montreal, Succ. Centre-Ville, Montreal, Quebec (Canada)

    2013-01-15

    Atrazine is frequently detected in freshwater ecosystems exposed to agricultural waste waters and runoffs worldwide and it can affect non-target organisms (mainly photoautotrophic) and modify community structure. Meanwhile, light environment is known to vary between aquatic ecosystems, but also before and during the exposure to atrazine and these variations may modify the sensitivity to atrazine of photoautotroph organisms. In this study, 10 species of phytoplankton (chlorophytes, baccilariophytes and cyanophytes) acclimated to low or high light intensities were exposed to atrazine and light of different intensities to compare their combined effect. Our data showed that chlorophytes and baccilariophytes were more resistant to atrazine compared to cyanophytes for all light conditions. Atrazine was found to inhibit {Phi}{sup Prime }{sub M}, {Psi}{sub 0}, P{sub M} and non-photochemical quenching for all species indicating an effect on electron transport, primary production and photoregulation processes. These data also indicate a higher sensitivity of {Psi}{sub 0} (average {Psi}{sub 0}-EC{sub 50} of 91 {+-} 11 nM or 19.6 {+-} 0.9 {mu}g L{sup -1}) compared to {Phi}{sup Prime }{sub M} (average {Phi}{sup Prime }{sub M}-EC{sub 50} of 217 {+-} 19 nM or 46.8 {+-} 4.1 {mu}g L{sup -1}) and suggest that photoregulation processes activated in presence of light decrease the effect of atrazine. We also showed that increasing light intensity decreased {Phi}{sup Prime }{sub M}-EC{sub 50} in both low (except baccilariophytes) and high light acclimated conditions. Despite this similarity, most species acclimated to high light were found to have higher or similar {Phi}{sup Prime }{sub M}-EC{sub 50} compared to low light acclimated cells and thus, were less sensitive to atrazine in low light and high light environments. We concluded that an increase in the plastoquinone pool induced by acclimation to high light decreased the sensitivity to atrazine in phytoplankton and we hypothesized

  9. THE CLASSIFICATION OF KEPLER B-STAR VARIABLES

    International Nuclear Information System (INIS)

    McNamara, Bernard J.; Jackiewicz, Jason; McKeever, Jean

    2012-01-01

    The light curves of 252 B-star candidates in the Kepler database are analyzed in a similar fashion to that done by Balona et al. to further characterize B-star variability, increase the sample of variable B stars for future study, and to identify stars whose power spectra include particularly interesting features such as frequency groupings. Stars are classified as either constant light emitters, β Cep stars, slowly pulsating B stars (SPBs), hybrid pulsators, binaries or stars whose light curves are dominated by rotation (Bin/Rot), hot subdwarfs, or white dwarfs. One-hundred stars in our sample were found to be either light constants or to be variable at a level of less than 0.02 mmag. We increase the number of candidate B-star variables found in the Kepler database by Balona et al. in the following fashion: β Cep stars from 0 to 10, SPBs from eight to 54, hybrid pulsators from seven to 21, and Bin/Rot stars from 23 to 82. For comparison purposes, approximately 51 SPBs and six hybrids had been known prior to 2007. The number of β Cep stars known prior to 2004 was 93. A secondary result of this study is the identification of an additional 11 pulsating white dwarf candidates, four of which possess frequency groupings.

  10. CSI 2264: CHARACTERIZING YOUNG STARS IN NGC 2264 WITH STOCHASTICALLY VARYING LIGHT CURVES

    Energy Technology Data Exchange (ETDEWEB)

    Stauffer, John; Rebull, Luisa; Carey, Sean [Spitzer Science Center, California Institute of Technology, Pasadena, CA 91125 (United States); Cody, Ann Marie [NASA Ames Research Center, Kepler Science Office, Mountain View, CA 94035 (United States); Hillenbrand, Lynne A.; Carpenter, John [Astronomy Department, California Institute of Technology, Pasadena, CA 91125 (United States); Turner, Neal J. [Jet Propulsion Laboratory, California Institute of Technology, Pasadena, CA 91109 (United States); Terebey, Susan [Department of Physics and Astronomy, 5151 State University Drive, California State University at Los Angeles, Los Angeles, CA 90032 (United States); Morales-Calderón, Maria [Centro de Astrobiología, Dpto. de Astrofísica, INTA-CSIC, P.O. BOX 78, E-28691, ESAC Campus, Villanueva de la Cañada, Madrid (Spain); Alencar, Silvia H. P.; McGinnis, Pauline; Sousa, Alana [Departamento de Física—ICEx—UFMG, Av. Antônio Carlos, 6627, 30270-901, Belo Horizonte, MG (Brazil); Bouvier, Jerome; Venuti, Laura [Université de Grenoble, Institut de Planétologie et d’Astrophysique de Grenoble (IPAG), F-38000 Grenoble (France); Hartmann, Lee; Calvet, Nuria [Department of Astronomy, University of Michigan, 500 Church Street, Ann Arbor, MI:48105 (United States); Micela, Giusi; Flaccomio, Ettore [INAF—Osservatorio Astronomico di Palermo, Piazza del Parlamento 1, I-90134, Palermo (Italy); Song, Inseok [Department of Physics and Astronomy, The University of Georgia, Athens, GA 30602-2451 (United States); Gutermuth, Rob, E-mail: stauffer@ipac.caltech.edu [Department of Astronomy, University of Massachusetts, Amherst, MA 01003 (United States); and others

    2016-03-15

    We provide CoRoT and Spitzer light curves and other supporting data for 17 classical T Tauri stars in NGC 2264 whose CoRoT light curves exemplify the “stochastic” light curve class as defined in 2014 by Cody et al. The most probable physical mechanism to explain the optical variability within this light curve class is time-dependent mass accretion onto the stellar photosphere, producing transient hot spots. Where we have appropriate spectral data, we show that the veiling variability in these stars is consistent in both amplitude and timescale with the optical light curve morphology. The veiling variability is also well-correlated with the strength of the He i 6678 Å emission line, predicted by models to arise in accretion shocks on or near the stellar photosphere. Stars with accretion burst light curve morphology also have variable mass accretion. The stochastic and accretion burst light curves can both be explained by a simple model of randomly occurring flux bursts, with the stochastic light curve class having a higher frequency of lower amplitude events. Members of the stochastic light curve class have only moderate mass accretion rates. Their Hα profiles usually have blueshifted absorption features, probably originating in a disk wind. The lack of periodic signatures in the light curves suggests that little of the variability is due to long-lived hot spots rotating into or out of our line of sight; instead, the primary driver of the observed photometric variability is likely to be instabilities in the inner disk that lead to variable mass accretion.

  11. A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth

    Energy Technology Data Exchange (ETDEWEB)

    Zhao, Shuli [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Nanjing Affiliated First Hospital, Nanjing Medical University, Nanjing (China); Zhao, Guangfeng; Xie, Hao; Huang, Yahong [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Hou, Yayi [Immunology and Reproductive Biology Laboratory, Medical School & State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing (China)

    2012-01-27

    Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex){sub 1.3}(DOX){sub 20}. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.

  12. A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth

    International Nuclear Information System (INIS)

    Zhao, Shuli; Zhao, Guangfeng; Xie, Hao; Huang, Yahong; Hou, Yayi

    2012-01-01

    Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex) 1.3 (DOX) 20 . In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8%) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83% inhibition vs 40.81%). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers

  13. Inhibition of DNA chain elongation in Chinese hamster cells by damage localized behind the replication fork

    Energy Technology Data Exchange (ETDEWEB)

    Ben-Hur, E [Israel Atomic Energy Commission, Beersheba. Nuclear Research Center-Negev; Hagan, M P [Armed Forces Radiobiology Research Inst., Bethesda, MD (USA)

    1984-05-01

    Chinese hamster fibroblasts were pulse labelled with 5-bromodeoxyuridine and exposed at time intervals (Tsub(i)) to near-ultraviolet (U.V.A.) light in the presence of a bisbenzimidazole derivative (Hoechst 33342). The sensitivity of the cells in terms of colony forming ability fluctuated depending on Tsub(i). Inhibition of DNA synthesis also depended on Tsub(i) and was maximal when Tsub(i)=O. Using the alkaline elution technique it was shown that the effect of a large dose of light was to inhibit both initiation and elongation of DNA chains. These effects were most pronounced for Tsub(i)=O. It is concluded that DNA damage in an active replicon can inhibit initiation of new replicons and that damage localized behind the replication fork can retard elongation of nascent DNA chains. This effect on chain elongation decreases with increased distance of the damage from the replication fork.

  14. The ASAS-SN Catalog of Variable Stars I: The Serendipitous Survey

    Science.gov (United States)

    Jayasinghe, T.; Kochanek, C. S.; Stanek, K. Z.; Shappee, B. J.; Holoien, T. W.-S.; Thompson, Todd A.; Prieto, J. L.; Dong, Subo; Pawlak, M.; Shields, J. V.; Pojmanski, G.; Otero, S.; Britt, C. A.; Will, D.

    2018-04-01

    The All-Sky Automated Survey for Supernovae (ASAS-SN) is the first optical survey to routinely monitor the whole sky with a cadence of ˜2 - 3 days down to V≲ 17 mag. ASAS-SN has monitored the whole sky since 2014, collecting ˜100 - 500 epochs of observations per field. The V-band light curves for candidate variables identified during the search for supernovae are classified using a random forest classifier and visually verified. We present a catalog of 66,533 bright, new variable stars discovered during our search for supernovae, including 27,753 periodic variables and 38,780 irregular variables. V-band light curves for the ASAS-SN variables are available through the ASAS-SN variable stars database (https://asas-sn.osu.edu/variables). The database will begin to include the light curves of known variable stars in the near future along with the results for a systematic, all-sky variability survey.

  15. Efficiency and Integration in the Food Supply Chain

    Directory of Open Access Journals (Sweden)

    Sebastian Jarzebowski

    2013-11-01

    Full Text Available Due to the nature of the food supply chain, an increase of the integration's degree in the chain may be an important aspect in the context of increasing the efficiency of agri-food companies. Therefore, exploring the relationships among these variables was found as an important research area and adopted as the goal of the paper. The paper is focused mainly on the theoretical background showing the relationship between integration and performance. A description of the theoretical and methodological aspects of performance measurement and its extension (including the integration aspect was also made within the framework of the paper.For an empirical illustration of the analyzed relationships two steps were made. Firstly, the integration's degree in the food chain was measured. Secondly, the efficiency of the companies from the cereals processing industry in Europe was assessed. The SFA models (e.g. Translog and Cobb-Douglas functional form were used for assessment of efficiency. By using stochastic method (e.g. the SFA, Stochastic Frontier Analysis, one may show the influence of external variable (the integration in the supply chain on the efficiency performance of enterprises. Efficiency of economic entities is not an unambiguous term. There are several different concepts of efficiency, its measurement and expressions. Within the framework of efficiency, many terms of similar meaning may be applied. However, these concepts are not identical. The actual concept of efficiency is derived from the structure of the production function, therefore it is conditioned by changes in the productivity of production factors and their remuneration and refers to the allocation of production factors in the most technically efficient way.

  16. Using mi impute chained to fit ANCOVA models in randomized trials with censored dependent and independent variables

    DEFF Research Database (Denmark)

    Andersen, Andreas; Rieckmann, Andreas

    2016-01-01

    In this article, we illustrate how to use mi impute chained with intreg to fit an analysis of covariance analysis of censored and nondetectable immunological concentrations measured in a randomized pretest–posttest design.......In this article, we illustrate how to use mi impute chained with intreg to fit an analysis of covariance analysis of censored and nondetectable immunological concentrations measured in a randomized pretest–posttest design....

  17. Logistics’ diagnostic in cosmetics and toiletries supply chain

    Directory of Open Access Journals (Sweden)

    Javier Arturo Orjuela-Castro

    2016-12-01

    Full Text Available The sector of cosmetics and toiletries is a world class sector, consolidated in Colombia with 690 companies of which 420 are in Bogotá D.C. Taking into account that logistics management generates competitive advantage in organizations as factor of success in a global economy, this paper proposes a logistics analysis applied to the case of cosmetics and toiletries supply chain. The results include the diagnosis of logistics processes and resources, which they were studied with an own methodology proposal. The methodology allowed study the logistics factors and variables, elements that recognized the logistical behaviour in the different links of the supply chain.

  18. An Integer Programming Model for Multi-Echelon Supply Chain Decision Problem Considering Inventories

    Science.gov (United States)

    Harahap, Amin; Mawengkang, Herman; Siswadi; Effendi, Syahril

    2018-01-01

    In this paper we address a problem that is of significance to the industry, namely the optimal decision of a multi-echelon supply chain and the associated inventory systems. By using the guaranteed service approach to model the multi-echelon inventory system, we develop a mixed integer; programming model to simultaneously optimize the transportation, inventory and network structure of a multi-echelon supply chain. To solve the model we develop a direct search approach using a strategy of releasing nonbasic variables from their bounds, combined with the “active constraint” method. This strategy is used to force the appropriate non-integer basic variables to move to their neighbourhood integer points.

  19. Structural plasticity of the N-terminal capping helix of the TPR domain of kinesin light chain.

    Directory of Open Access Journals (Sweden)

    The Quyen Nguyen

    Full Text Available Kinesin1 plays a major role in neuronal transport by recruiting many different cargos through its kinesin light chain (KLC. Various structurally unrelated cargos interact with the conserved tetratricopeptide repeat (TPR domain of KLC. The N-terminal capping helix of the TPR domain exhibits an atypical sequence and structural features that may contribute to the versatility of the TPR domain to bind different cargos. We determined crystal structures of the TPR domain of both KLC1 and KLC2 encompassing the N-terminal capping helix and show that this helix exhibits two distinct and defined orientations relative to the rest of the TPR domain. Such a difference in orientation gives rise, at the N-terminal part of the groove, to the formation of one hydrophobic pocket, as well as to electrostatic variations at the groove surface. We present a comprehensive structural analysis of available KLC1/2-TPR domain structures that highlights that ligand binding into the groove can be specific of one or the other N-terminal capping helix orientations. Further, structural analysis reveals that the N-terminal capping helix is always involved in crystal packing contacts, especially in a TPR1:TPR1' contact which highlights its propensity to be a protein-protein interaction site. Together, these results underline that the structural plasticity of the N-terminal capping helix might represent a structural determinant for TPR domain structural versatility in cargo binding.

  20. SUPPLY CHAIN STRATEGIES IN THE CONTEXT OF AN E-COMMERCE CHAIN (E-CHAIN

    Directory of Open Access Journals (Sweden)

    João Gilberto Mendes do Reis

    2014-05-01

    Full Text Available This paper purpose to explore the relationships between supply chain strategies and product performance in retail e-commerce. In this case, we concern that in current, in order to bear up under competition, organizations have to manage their supply chains so that they meet the needs of their final customers. With this concept in mind, the research presented in this study focuses on establishing the right strategy for supply chains according to their product segment. Thus, after a Literature Review, the paper explain a methodology based in different authors studies. Finally the article focuses on a pratical case in e-commerce retail that describes its application in this field. The research shows that it is possible to use a methodology for classifying supply chains using chain strategies and product features. The use of the right strategy for supply chains will improve the competitive advantage of businesses. One limitation is that the methodology study focuses on only two e-commerce segment; future studies may go further in refining the proposed framework for other segments. The aim of this research is to offer businesses a model for evaluating supply chains, allowing them to improve the performance of their products and services by using the right strategy for supply chains. The classification proposal of this paper presents an original model for classification of supply chains based on different studies on the theme.

  1. Haloes and clustering in light, neutron-rich nuclei

    International Nuclear Information System (INIS)

    Orr, N.A.

    2001-10-01

    Clustering is a relatively widespread phenomenon which takes on many guises across the nuclear landscape. Selected topics concerning the study of halo systems and clustering in light, neutron-rich nuclei are discussed here through illustrative examples taken from the Be isotopic chain. (author)

  2. Probabilistic Assessment of Investment Options in Honey Value Chains in Lamu County, Kenya

    Directory of Open Access Journals (Sweden)

    Joshua Wafula

    2018-03-01

    Full Text Available Designing and implementing biodiversity-based value chains can be a complex undertaking, especially in places where outcomes are uncertain and risks of project failure and cost overruns are high. We used the Stochastic Impact Evaluation (SIE approach to guide the Intergovernmental Authority on Development (IGAD on viable investment options in honey value chains, which the agency considered implementing as an economic incentive for communities along the Kenya-Somalia border to conserve biodiversity. The SIE approach allows for holistic analysis of project cost, benefit, and risk variables, including those with uncertain and missing information. It also identifies areas that pose critical uncertainties in the project. We started by conducting a baseline survey in Witu and Awer in Lamu County, Kenya. The aim of the survey was to establish the current farm income from beekeeping as a baseline, against which the prospective impacts of intervention options could be measured. We then developed an intervention decision model that was populated with all cost, benefit and risk variables relevant to beekeeping. After receiving training in making quantitative estimates, four subject-matter experts expressed their uncertainty about the proposed variables in the model by specifying probability distributions for them. We then used Monte Carlo simulation to project decision outcomes. We also identified variables that projected decision outcomes were most sensitive to, and we determined the value of information for each variable. The variable with the highest information value to the decision-maker in Witu was the honey price. In Awer, no additional information on any of the variables would change the recommendation to invest in honey value chains in the region. The analysis demonstrates a novel and comprehensive approach to decision-making for different stakeholders in a project where decision outcomes are uncertain.

  3. From Chains for Mean Value Inequalities to Mitrinovic's Problem II

    Science.gov (United States)

    Zhu, Ling

    2005-01-01

    In this note, an integrated form of some significant means with two variables is provided, and some chains for mean value inequalities are obtained. At the same time, a concise family of algebraic functions appears, which satisfy Mitrinovic's requirements.

  4. Variable Stars in the Field of V729 Aql

    Science.gov (United States)

    Cagaš, P.

    2017-04-01

    Wide field instruments can be used to acquire light curves of tens or even hundreds of variable stars per night, which increases the probability of new discoveries of interesting variable stars and generally increases the efficiency of observations. At the same time, wide field instruments produce a large amount of data, which must be processed using advanced software. The traditional approach, typically used by amateur astronomers, requires an unacceptable amount of time needed to process each data set. New functionality, built into SIPS software package, can shorten the time needed to obtain light curves by several orders of magnitude. Also, newly introduced SILICUPS software is intended for post-processing of stored light curves. It can be used to visualize observations from many nights, to find variable star periods, evaluate types of variability, etc. This work provides an overview of tools used to process data from the large field of view around the variable star V729 Aql. and demonstrates the results.

  5. China's Rare Earth Supply Chain: Illegal Production, and Response to new Cerium Demand

    Science.gov (United States)

    Nguyen, Ruby Thuy; Imholte, D. Devin

    2016-07-01

    As the demand for personal electronic devices, wind turbines, and electric vehicles increases, the world becomes more dependent on rare earth elements. Given the volatile, Chinese-concentrated supply chain, global attempts have been made to diversify supply of these materials. However, the overall effect of supply diversification on the entire supply chain, including increasing low-value rare earth demand, is not fully understood. This paper is the first attempt to shed some light on China's supply chain from both demand and supply perspectives, taking into account different Chinese policies such as mining quotas, separation quotas, export quotas, and resource taxes. We constructed a simulation model using Powersim Studio that analyzes production (both legal and illegal), production costs, Chinese and rest-of-world demand, and market dynamics. We also simulated new demand of an automotive aluminum-cerium alloy in the US market starting from 2018. Results showed that market share of the illegal sector has grown since 2007-2015, ranging between 22% and 25% of China's rare earth supply, translating into 59-65% illegal heavy rare earths and 14-16% illegal light rare earths. There will be a shortage in certain light and heavy rare earths given three production quota scenarios and constant demand growth rate from 2015 to 2030. The new simulated Ce demand would require supply beyond that produced in China. Finally, we illustrate revenue streams for different ore compositions in China in 2015.

  6. Incidence and outcome of patients starting renal replacement therapy for end-stage renal disease due to multiple myeloma or light-chain deposit disease: an ERA-EDTA Registry study

    DEFF Research Database (Denmark)

    Tsakiris, D.J.; Stel, V.S.; Finne, P.

    2010-01-01

    Background. Information on demographics and survival of patients starting renal replacement therapy (RRT) for end-stage renal disease (ESRD) due to multiple myeloma (MM) or light-chain deposit disease (LCDD) is scarce. The aim of this study was to describe the incidence, characteristics, causes...... causes (non-MM) was observed overtime. Patient survival on RRT was examined, unadjusted and adjusted for age and gender. Results. Of the 159 637 patients on RRT, 2453 (1.54%) had MM or LCDD. The incidence of RRT for ESRD due to MM or LCDD, adjusted for age and gender, increased from 0.70 pmp in 1986...

  7. Optical design of adjustable light emitting diode for different lighting requirements

    International Nuclear Information System (INIS)

    Lu Jia-Ning; Yu Jie; Tong Yu-Zhen; Zhang Guo-Yi

    2012-01-01

    Light emitting diode (LED) sources have been widely used for illumination. Optical design, especially freedom compact lens design is necessary to make LED sources applied in lighting industry, such as large-range interior lighting and small-range condensed lighting. For different lighting requirements, the size of target planes should be variable. In our paper we provide a method to design freedom lens according to the energy conservation law and Snell law through establishing energy mapping between the luminous flux emitted by a Lambertian LED source and a certain area of the target plane. The algorithm of our design can easily change the radius of each circular target plane, which makes the size of the target plane adjustable. Ray-tracing software Tracepro is used to validate the illuminance maps and polar-distribution maps. We design lenses for different sizes of target planes to meet specific lighting requirements. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  8. Light-Front Holography and the Light-Front Schrodinger Equation

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, Stanley J.; de Teramond, Guy

    2012-08-15

    One of the most important nonperturbative methods for solving QCD is quantization at fixed light-front time {tau} = t+z=c - Dirac's 'Front Form'. The eigenvalues of the light-front QCD Hamiltonian predict the hadron spectrum and the eigensolutions provide the light-front wavefunctions which describe hadron structure. More generally, we show that the valence Fock-state wavefunctions of the light-front QCD Hamiltonian satisfy a single-variable relativistic equation of motion, analogous to the nonrelativistic radial Schrodinger equation, with an effective confining potential U which systematically incorporates the effects of higher quark and gluon Fock states. We outline a method for computing the required potential from first principles in QCD. The holographic mapping of gravity in AdS space to QCD, quantized at fixed light-front time, yields the same light front Schrodinger equation; in fact, the soft-wall AdS/QCD approach provides a model for the light-front potential which is color-confining and reproduces well the light-hadron spectrum. One also derives via light-front holography a precise relation between the bound-state amplitudes in the fifth dimension of AdS space and the boost-invariant light-front wavefunctions describing the internal structure of hadrons in physical space-time. The elastic and transition form factors of the pion and the nucleons are found to be well described in this framework. The light-front AdS/QCD holographic approach thus gives a frame-independent first approximation of the color-confining dynamics, spectroscopy, and excitation spectra of relativistic light-quark bound states in QCD.

  9. Superconducting Undulator with Variably Polarized Light

    CERN Document Server

    Hwang, Ching Shiang; Ching Fan, Tai; Li, W P; Lin, P H

    2004-01-01

    This study investigates planar in-vacuo superconducting undulators with periodic length of 5 cm (IVSU5) producing linearly and circularly polarized infrared rays or xrays source. The vertically wound racetrack coil is selected for the coil and pole fabrication of the IVSU5. When the up and down magnetic pole arrays with alternative directions rotated wires in the horizontal plane, a helical field radiates circularly polarized light in the electron storage ring, the free electron laser (FEL), and the energy recovery linac (ERL) facilities. Meanwhile, an un-rotated wire is constructed together with the rotated wire on the same undulator is used to switch the linear horizontal and vertical, the right- and left-circular polarization radiation. Given a periodic length of 5 cm and a gap of 23 mm, the maximum magnetic flux density in the helical undulator are Bz = 1.5 T and Bx = 0.5 T when the wires rotated by 20°. This article describes the main factors of the planar and helical undulator design for FEL and...

  10. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics

    Directory of Open Access Journals (Sweden)

    Peter Bannas

    2017-11-01

    Full Text Available Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL. The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL. VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv. scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa and nanobody-based human heavy chain antibodies (75 kDa can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb. Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo. Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo. Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody

  11. Nanobodies and Nanobody-Based Human Heavy Chain Antibodies As Antitumor Therapeutics.

    Science.gov (United States)

    Bannas, Peter; Hambach, Julia; Koch-Nolte, Friedrich

    2017-01-01

    Monoclonal antibodies have revolutionized cancer therapy. However, delivery to tumor cells in vivo is hampered by the large size (150 kDa) of conventional antibodies. The minimal target recognition module of a conventional antibody is composed of two non-covalently associated variable domains (VH and VL). The proper orientation of these domains is mediated by their hydrophobic interface and is stabilized by their linkage to disulfide-linked constant domains (CH1 and CL). VH and VL domains can be fused via a genetic linker into a single-chain variable fragment (scFv). scFv modules in turn can be fused to one another, e.g., to generate a bispecific T-cell engager, or they can be fused in various orientations to antibody hinge and Fc domains to generate bi- and multispecific antibodies. However, the inherent hydrophobic interaction of VH and VL domains limits the stability and solubility of engineered antibodies, often causing aggregation and/or mispairing of V-domains. Nanobodies (15 kDa) and nanobody-based human heavy chain antibodies (75 kDa) can overcome these limitations. Camelids naturally produce antibodies composed only of heavy chains in which the target recognition module is composed of a single variable domain (VHH or Nb). Advantageous features of nanobodies include their small size, high solubility, high stability, and excellent tissue penetration in vivo . Nanobodies can readily be linked genetically to Fc-domains, other nanobodies, peptide tags, or toxins and can be conjugated chemically at a specific site to drugs, radionuclides, photosensitizers, and nanoparticles. These properties make them particularly suited for specific and efficient targeting of tumors in vivo . Chimeric nanobody-heavy chain antibodies combine advantageous features of nanobodies and human Fc domains in about half the size of a conventional antibody. In this review, we discuss recent developments and perspectives for applications of nanobodies and nanobody-based human heavy

  12. Non-classical light emission from single conjugated polymers

    Science.gov (United States)

    Hollars, Christopher; Lane, Stephen; Huser, Thomas

    2002-03-01

    Photon-antibunching from single, isolated molecules of collapsed-chain poly[2-methoxy,5-(2’-ethyl-hexyloxy)-p-phenylene-vinylene] (MEH-PPV) has been observed using confocal microscopy techniques. Efficient inter-segment energy transfer in collapsed-chain conjugated polymers leads to emission from an average of only 2-3 active sites on a polymer chain that is composed of hundreds of quasi-chromophores. These few centers consist of the segments with the lowest excitation energy and are supplied by the efficient light-harvesting and energy transfer of the surrounding higher-energy segments. This effect depends on the conformation of the polymer molecules, which is controlled by solvent polarity. These results provide new insight into the controversial photophysics of conjugated polymers and their application in optoelectronic devices.

  13. Facile Synthesis of Worm-like Micelles by Visible Light Mediated Dispersion Polymerization Using Photoredox Catalyst.

    Science.gov (United States)

    Yeow, Jonathan; Xu, Jiangtao; Boyer, Cyrille

    2016-06-08

    Presented herein is a protocol for the facile synthesis of worm-like micelles by visible light mediated dispersion polymerization. This approach begins with the synthesis of a hydrophilic poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA) homopolymer using reversible addition-fragmentation chain-transfer (RAFT) polymerization. Under mild visible light irradiation (λ = 460 nm, 0.7 mW/cm(2)), this macro-chain transfer agent (macro-CTA) in the presence of a ruthenium based photoredox catalyst, Ru(bpy)3Cl2 can be chain extended with a second monomer to form a well-defined block copolymer in a process known as Photoinduced Electron Transfer RAFT (PET-RAFT). When PET-RAFT is used to chain extend POEGMA with benzyl methacrylate (BzMA) in ethanol (EtOH), polymeric nanoparticles with different morphologies are formed in situ according to a polymerization-induced self-assembly (PISA) mechanism. Self-assembly into nanoparticles presenting POEGMA chains at the corona and poly(benzyl methacrylate) (PBzMA) chains in the core occurs in situ due to the growing insolubility of the PBzMA block in ethanol. Interestingly, the formation of highly pure worm-like micelles can be readily monitored by observing the onset of a highly viscous gel in situ due to nanoparticle entanglements occurring during the polymerization. This process thereby allows for a more reproducible synthesis of worm-like micelles simply by monitoring the solution viscosity during the course of the polymerization. In addition, the light stimulus can be intermittently applied in an ON/OFF manner demonstrating temporal control over the nanoparticle morphology.

  14. Cataclysmic Variable Stars

    Science.gov (United States)

    Hellier, Coel

    2001-01-01

    Cataclysmic variable stars are the most variable stars in the night sky, fluctuating in brightness continually on timescales from seconds to hours to weeks to years. The changes can be recorded using amateur telescopes, yet are also the subject of intensive study by professional astronomers. That study has led to an understanding of cataclysmic variables as binary stars, orbiting so closely that material transfers from one star to the other. The resulting process of accretion is one of the most important in astrophysics. This book presents the first account of cataclysmic variables at an introductory level. Assuming no previous knowledge of the field, it explains the basic principles underlying the variability, while providing an extensive compilation of cataclysmic variable light curves. Aimed at amateur astronomers, undergraduates, and researchers, the main text is accessible to those with no mathematical background, while supplementary boxes present technical details and equations.

  15. Spin chain and duality between string theory and gauge theories

    International Nuclear Information System (INIS)

    Gorskij, A.S.

    2005-01-01

    One discusses a string pattern hidden by the integrable spin chains describing the evolution equations in the Yang- Mills theory. It is shown that the single-loop correction to the dilatation operator in N = 4 theory may be expressed in terms of two-point correlation functions at two-dimensional world surface of a string. Correspondence between the Neumann integrable systems and the spin chains leads us to believe that passing to the finite values of the coupling constants in the gauge theory corresponds to the quantization of the world surface. The model of string bits for the digitized world surface is assumed to be in line with representation of the integrable spin chains in terms of the separable variables [ru

  16. Novel Strategy for Photopatterning Emissive Polymer Brushes for Organic Light Emitting Diode Applications.

    Science.gov (United States)

    Page, Zachariah A; Narupai, Benjaporn; Pester, Christian W; Bou Zerdan, Raghida; Sokolov, Anatoliy; Laitar, David S; Mukhopadhyay, Sukrit; Sprague, Scott; McGrath, Alaina J; Kramer, John W; Trefonas, Peter; Hawker, Craig J

    2017-06-28

    A light-mediated methodology to grow patterned, emissive polymer brushes with micron feature resolution is reported and applied to organic light emitting diode (OLED) displays. Light is used for both initiator functionalization of indium tin oxide and subsequent atom transfer radical polymerization of methacrylate-based fluorescent and phosphorescent iridium monomers. The iridium centers play key roles in photocatalyzing and mediating polymer growth while also emitting light in the final OLED structure. The scope of the presented procedure enables the synthesis of a library of polymers with emissive colors spanning the visible spectrum where the dopant incorporation, position of brush growth, and brush thickness are readily controlled. The chain-ends of the polymer brushes remain intact, affording subsequent chain extension and formation of well-defined diblock architectures. This high level of structure and function control allows for the facile preparation of random ternary copolymers and red-green-blue arrays to yield white emission.

  17. Lemur tyrosine kinase-2 signalling regulates kinesin-1 light chain-2 phosphorylation and binding of Smad2 cargo.

    LENUS (Irish Health Repository)

    Manser, C

    2012-05-31

    A recent genome-wide association study identified the gene encoding lemur tyrosine kinase-2 (LMTK2) as a susceptibility gene for prostate cancer. The identified genetic alteration is within intron 9, but the mechanisms by which LMTK2 may impact upon prostate cancer are not clear because the functions of LMTK2 are poorly understood. Here, we show that LMTK2 regulates a known pathway that controls phosphorylation of kinesin-1 light chain-2 (KLC2) by glycogen synthase kinase-3β (GSK3β). KLC2 phosphorylation by GSK3β induces the release of cargo from KLC2. LMTK2 signals via protein phosphatase-1C (PP1C) to increase inhibitory phosphorylation of GSK3β on serine-9 that reduces KLC2 phosphorylation and promotes binding of the known KLC2 cargo Smad2. Smad2 signals to the nucleus in response to transforming growth factor-β (TGFβ) receptor stimulation and transport of Smad2 by kinesin-1 is required for this signalling. We show that small interfering RNA loss of LMTK2 not only reduces binding of Smad2 to KLC2, but also inhibits TGFβ-induced Smad2 signalling. Thus, LMTK2 may regulate the activity of kinesin-1 motor function and Smad2 signalling.

  18. Review of Coconut “Lethal Yellowing” type diseases Diversity, variability and diagnosis

    Directory of Open Access Journals (Sweden)

    Dollet Michel

    2009-03-01

    Full Text Available Coconut palms (Cocos nucifera L. can be affected by several types of Lethal Yellowing (LY diseases worldwide. Some of the syndromes are caused by phytoplasmas, small bacteria that are impossible to detect by light microscopy. Amplification of a given gene of the phytoplasmas by polymerase chain reaction (PCR is the most convenient diagnosis method. The problem is that there are at least 28 “groups” of phytoplasmas and only one pair of primers -P1/P7- commonly used for PCR. As these primers belong to a very conserved gene, false positives are frequent. Consequently, alternative primers specific to one “strain” (or subgroup have to be used, such as LY-F/LY-R for the Caribbean LY, Rohde primers for LD Tanzania. Such specific primers are sometimes restrictive. Indeed, there is variability within each strain and the sequence of the primers has to be adapted to that variability. There are at least five LY subgroups. The subgroups can only be identified by restriction fragment length polymorphism or sequencing. In Africa, two subgroups of LY phytoplasmas have been identified so far.

  19. Single chain variable fragment antibodies block aggregation and toxicity induced by familial ALS-linked mutant forms of SOD1.

    Science.gov (United States)

    Ghadge, Ghanashyam D; Pavlovic, John D; Koduvayur, Sujatha P; Kay, Brian K; Roos, Raymond P

    2013-08-01

    Approximately 10% of amyotrophic lateral sclerosis (ALS) cases are familial (known as FALS) with an autosomal dominant inheritance pattern, and ~25% of FALS cases are caused by mutations in Cu/Zn superoxide dismutase (SOD1). There is convincing evidence that mutant SOD1 (mtSOD1) kills motor neurons (MNs) because of a gain-of-function toxicity, most likely related to aggregation of mtSOD1. A number of recent reports have suggested that antibodies can be used to treat mtSOD1-induced FALS. To follow up on the use of antibodies as potential therapeutics, we generated single chain fragments of variable region antibodies (scFvs) against SOD1, and then expressed them as 'intrabodies' within a motor neuron cell line. In the present study, we describe isolation of human scFvs that interfere with mtSOD1 in vitro aggregation and toxicity. These scFvs may have therapeutic potential in sporadic ALS, as well as FALS, given that sporadic ALS may also involve abnormalities in the SOD1 protein or activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Genetic variability in Brazilian populations of Biomphalaria straminea complex detected by simple sequence repeat anchored polymerase chain reaction amplification

    Directory of Open Access Journals (Sweden)

    Caldeira Roberta L

    2001-01-01

    Full Text Available Biomphalaria glabrata, B. tenagophila and B. straminea are intermediate hosts of Schistosoma mansoni, in Brazil. The latter is of epidemiological importance in the northwest of Brazil and, due to morphological similarities, has been grouped with B. intermedia and B. kuhniana in a complex named B. straminea. In the current work, we have standardized the simple sequence repeat anchored polymerase chain reaction (SSR-PCR technique, using the primers (CA8RY and K7, to study the genetic variability of these species. The similarity level was calculated using the Dice coefficient and genetic distance using the Nei and Li coefficient. The trees were obtained by the UPGMA and neighbor-joining methods. We have observed that the most related individuals belong to the same species and locality and that individuals from different localities, but of the same species, present clear heterogeneity. The trees generated using both methods showed similar topologies. The SSR-PCR technique was shown to be very efficient in intrapopulational and intraspecific studies of the B. straminea complex snails.

  1. Use of calorie information at fast-food and chain restaurants among US adults, 2009.

    Science.gov (United States)

    Wethington, Holly; Maynard, Leah M; Haltiwanger, Christine; Blanck, Heidi M

    2014-09-01

    The aim of this study was to examine reading and use of calorie information at fast-food/chain restaurants. A cross-sectional analysis was conducted on a sample of 4363 US adults using the 2009 HealthStyles survey. The outcome variable was reading calorie information when available while ordering at fast-food/chain restaurants. Among those who go to fast-food/chain restaurants, we conducted multivariable logistic regression to examine associations between sociodemographic variables and reading calorie information when available. Among those who report reading calorie information when available, we assessed the proportion using calorie information. Among those who reported eating at fast-food/chain restaurants, 36.4% reported reading calorie information when available. Reading calorie information was not related to race/ethnicity, income or education. Compared with men, women had higher odds [adjusted odds ratio (OR) = 1.8; 95% confidence interval (CI) = 1.5-2.1] of reading calorie information when available while those who frequented fast-food/chain restaurants ≥3 times/week (aOR = 0.6; 95% CI = 0.4-0.8) had lower odds compared with those going Health 2013. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  2. Influence of light, UV-B radiation, and herbicides on wax biosynthesis of cucumber seedlings

    International Nuclear Information System (INIS)

    Tevini, M.; Steinmüller, D.

    1987-01-01

    The behavior of cuticular alkane-1-ols and alkanes were studied in different developmental stages of cucumber seedlings grown in the dark or under white light, with or without UV-B radiation or in presence of wax biosynthesis inhibitors, trichloroacetic acid and metolachlor. Accumulation of alkane-1-ols increased light independently with seedling age. Synthesis of alkanes was strictly light and dose dependent. Addition of UV-B radiation did not alter the amounts of alkanes or alcohols, however, the distribution of homologues was shifted towards shorter chain homologues. Treatments with Cl 3 AcOH resulted in strong inhibition of alkane accumulation, whereas the amount of alkane-1-ols was changed neither at low nor at moderate concentrations of Cl 3 AcOH but their homologue distribution shifted towards longer chain lengths. This shifting was depressed in the presence of UV-B. At high concentrations of Cl 3 Ac0H similar homologue distributions as produced by UV-B (shift to shorter homologues) were observed. Metolachlor treatment resulted in an inhibition of alkane-1-ol production connected with rising amounts of alkanes, predominantly of short chain species. A simple model of wax biosynthesis is proposed which describes the interactions with white light, UV-B radiation and herbicides. (author)

  3. Multiperiodicity in the light curve of Alpha Orionis

    International Nuclear Information System (INIS)

    Karovska, M.

    1987-01-01

    Alpha Ori, a supergiant star classified as M2 Iab, is characterized by pronounced variability encompassing most of its observed parameters. Variability on two different time scales has been observed in the light and velocity curves: a long period variation of about 6 years and superposed on this, irregular fluctuations having a time scale of several hundred days. This paper reports the results of Fourier analysis of more than 60- years of AAVSO (American Association of Variable Stars Observers) data which suggest a multiperiodicity in the light curve of α Ori

  4. Calculus light

    CERN Document Server

    Friedman, Menahem

    2011-01-01

    Another Calculus book? As long as students find calculus scary, the failure rate in mathematics is higher than in all other subjects, and as long as most people mistakenly believe that only geniuses can learn and understand mathematics, there will always be room for a new book of Calculus. We call it Calculus Light. This book is designed for a one semester course in ""light"" calculus -- mostly single variable, meant to be used by undergraduate students without a wide mathematical background and who do not major in mathematics but study subjects such as engineering, biology or management infor

  5. A novel smart lighting clinical testbed.

    Science.gov (United States)

    Gleason, Joseph D; Oishi, Meeko; Simkulet, Michelle; Tuzikas, Arunas; Brown, Lee K; Brueck, S R J; Karlicek, Robert F

    2017-07-01

    A real-time, feedback-capable, variable spectrum lighting system was recently installed at the University of New Mexico Hospital to facilitate biomedical research on the health impacts of lighting. The system consists of variable spectrum troffers, color sensors, occupancy sensors, and computing and communication infrastructure, and is the only such clinical facility in the US. The clinical environment posed special challenges for installation as well as for ongoing maintenance and operations. Pilot studies are currently underway to evaluate the effectiveness of the system to regulate circadian phase in subjects with delayed sleep-wake phase disorder.

  6. Effects of Supply Chain Risk Management on Organization Performance: Case of Andy Forwarders Services Limited

    OpenAIRE

    Caroline Wanjiru Munyuko

    2015-01-01

    The purpose of the research was to determine the effects of Supply chain risk management on organization performance. Previous studies have focused on risk management within the general context of an organization but little attention has been focused on how supply chain risk affect organization performance in terms of its bottom line profits and overall organization objectives. Particular attention was paid to the effects of supply chain risk management variables to the performance of the org...

  7. Adsorption of polymer chains at penetrable interfaces

    International Nuclear Information System (INIS)

    Gerasimchuk, I. V.; Sommer, J.-U.; Gerasimchuk, V. S.

    2011-01-01

    We investigate the problem of adsorption (localization) of polymer chains in the system of two penetrable interfaces within the mean-field approximation. The saturation of the polymer system in the limit case of zero bulk concentration is studied. We find the exact solution of this mean-field polymer adsorption problem that opens the possibility to treat various localization problems for polymer chains in such environments using appropriate boundary conditions. The exact solution is controlled by a single scaling variable that describes the coupling between the interfaces due to the polymer chains. We obtain a nonmonotonic behavior of the amount of adsorbed polymers as a function of the distance between the interfaces. This leads to a high-energy and a low-energy phase for the double layer with respect to the amount of polymers localized. At the saturation point, we find the total energy of the system and determine the force acting between the interfaces to be strictly attractive and to monotonically decay to zero when the interface distance increases.

  8. Modeling Water Clarity and Light Quality in Oceans

    Science.gov (United States)

    Phytoplankton is a primary producer of organic compounds, and it forms the base of the food chain in ocean waters. The concentration of phytoplankton in the water column controls water clarity and the amount and quality of light that penetrates through it. The availability of ade...

  9. Form factors of the finite quantum XY-chain

    International Nuclear Information System (INIS)

    Iorgov, Nikolai

    2011-01-01

    Explicit factorized formulas for the matrix elements (form factors) of the spin operators σ x and σ y between the eigenvectors of the Hamiltonian of the finite quantum periodic XY-chain in a transverse field were derived. The derivation is based on the relations between three models: the model of quantum XY-chain, Ising model on 2D lattice and N = 2 Baxter-Bazhanov-Stroganov τ (2) -model. Due to these relations we transfer the formulas for the form factors of the latter model recently obtained by the use of separation of variables method to the model of quantum XY-chain. Hopefully, the formulas for the form factors will help in analysis of multipoint dynamic correlation functions at a finite temperature. As an example, we re-derive the asymptotics of the two-point correlation function in the disordered phase without the use of the Toeplitz determinants and the Wiener-Hopf factorization method.

  10. Decision-Making for Supply Chain Integration Supply Chain Integration

    CERN Document Server

    Lettice, Fiona; Durowoju, Olatunde

    2012-01-01

    Effective supply chain integration, and the tight co-ordination it creates, is an essential pre-requisite for successful supply chain management.  Decision-Making for Supply Chain Integration is a practical reference on recent research in the area of supply chain integration focusing on distributed decision-making problems. Recent applications of various decision-making tools for integrating supply chains are covered including chapters focusing on: •Supplier selection, pricing strategy and inventory decisions in multi-level supply chains, •RFID-enabled distributed decision-making, •Operational risk issues and time-critical decision-making for sensitive logistics nodes, Modelling end to end processes to improve supply chain integration, and •Integrated systems to improve service delivery and optimize resource use. Decision-Making for Supply Chain Integration provides an insight into the tools and methodologies of this field with support from real-life case studies demonstrating successful application ...

  11. Simulation and assessment of agricultural biomass supply chain systems

    Directory of Open Access Journals (Sweden)

    D. Pavlou

    2017-05-01

    Full Text Available Agricultural biomass supply chain consists of a number of interacted sequential operations affected by various variables, such as weather conditions, machinery systems, and biomass features. These facts make the process of biomass supply chain as a complex system that requires computational tools, e.g. simulation and mathematical models, for their assessment and analysis. A biomass supply chain simulation model developed on the ExtendSim 8 simulation environment is presented in this paper. A number of sequential operations are applied in order biomass to be mowed, harvested, and transported to a biorefinery facility. Different operational scenarios regarding the travel distance between field and biorefinery facility, number of machines, and capacity of machines are analyzed showing how different parameters affect the processes within biomass supply chain in terms of time and cost. The results shown that parameters such as area of the field, travel distance, number of available machines, capacity of the machines, etc. should be taken into account in order a less time and/ or cost consuming machinery combination to be selected.

  12. Enhancing the Photoluminescence Emission of Conjugated MEH-PPV by Light Processing

    KAUST Repository

    Botiz, Ioan

    2014-04-09

    We show here that treatment of thin films of conjugated polymers by illumination with light leads to an increase of the intensity of their photoluminescence by up to 42%. The corresponding enhancement of absorbance was much less pronounced. We explain this significant enhancement of photoluminescence by a planarization of the conjugated polymer chains induced by photoexcitations even below the glass transition temperature, possibly due to an increased conjugation length. Interestingly, the photoluminescence remains at the enhanced level for more than 71 h after treatment of the films by illumination with light, likely due to the fact that below the glass transition temperature no restoring force could return the conjugated chains into their initial conformational state. © 2014 American Chemical Society.

  13. Expression, production and renaturation of a functional single-chain ...

    African Journals Online (AJOL)

    The single-chain variable antibody fragment (scFv) against human intercellular adhesion molecule-1 (ICAM-1) was expressed at a high level in Escherichia coli as inclusion bodies. We attempted to refold the scFv by ion-exchange chromatography (IEC), dialysis and dilution. The results show that the column ...

  14. From light to knowledge

    CERN Multimedia

    Globe Info

    2011-01-01

    An evening in two parts with Fabio Barblan. 1/ Light in daily life and what light means for an astronomer (exhibition). 2/ Light in all its states or how to extract information from the heavenly bodies: exploration using telescopes, space probes, spectrometry and imagery. Measuring and modelling using light (physical parameters, distances, etc.) Fabio Barblan is "an external scientific collaborator" and member of the photometry, stellar variability and GAIA group at the Observatoire de Genève. Observatoire de Genève Friday 14 October from 8:30 p.m. to 10:00 p.m. » Suitable for all – Admission free - Lecture in French For further information: +33 (0)4 50 41 96 80

  15. Growth and temperature dependent photoluminescence of InGaAs quantum dot chains

    International Nuclear Information System (INIS)

    Yang, Haeyeon; Kim, Dong-Jun; Colton, John S.; Park, Tyler; Meyer, David; Jones, Aaron M.; Thalman, Scott; Smith, Dallas; Clark, Ken; Brown, Steve

    2014-01-01

    Highlights: • We examine the optical properties of novel quantum dot chains. • Study shows that platelets evolve into quantum dots during heating of the InGaAs platelets encapsulated with GaAs. • Single stack of quantum dots emits light at room temperature. • Quantum dots are of high quality, confirmed by cross-section TEM images and photoluminescence. • Light emission at room temperature weakens beyond the detection limit when the quantum dots form above the critical annealing temperature. - Abstract: We report a study of growth and photoluminescence from a single stack of MBE-grown In 0.4 Ga 0.6 As quantum dot chains. The InGaAs epilayers were grown at a low temperature so that the resulting surfaces remain flat with platelets even though their thicknesses exceed the critical thickness of the conventional Stranski–Krastanov growth mode. The flat InGaAs layers were then annealed at elevated temperatures to induce the formation of quantum dot chains. A reflection high energy electron diffraction study suggests that, when the annealing temperature is at or below 480 °C, the surface of growth front remains flat during the periods of annealing and growth of a 10 nm thick GaAs capping layer. Surprisingly, transmission electron microscopy images do indicate the formation of quantum dot chains, however, so the dot-chains in those samples may form from precursory platelets during the period of temperature ramping and subsequent capping with GaAs due to intermixing of group III elements. The optical emission from the quantum dot layer demonstrates that there is a critical annealing temperature of 480–500 °C above which the properties of the low temperature growth approach are lost, as the optical properties begin to resemble those of quantum dots produced by the conventional Stranski–Krastanov technique

  16. Characterization of amylose nanoparticles prepared via nanoprecipitation: Influence of chain length distribution.

    Science.gov (United States)

    Chang, Yanjiao; Yang, Jingde; Ren, Lili; Zhou, Jiang

    2018-08-15

    The influence of chain length distribution of amylose on size and structure of the amylose nanoparticles (ANPs) prepared through nanoprecipitation was investigated. Amylose with different chain length distributions was obtained by β-amylase treating amylose paste for different times and measured by size exclusion chromatography (SEC) and fluorophore-assisted carbohydrate electrophoresis (FACE). ANPs prepared via precipitation were characterized by using dynamic light scattering (DLS), scanning electron microscopy (SEM) and X-ray diffraction (XRD). Results showed that the β-amylase treatments led to decrease in chain length of amylose, and it was the most important factor affecting size of ANPs. When hydrolysis degree of amylose was 52.8%, mean size of ANPs decreased from 206.4 nm to 102.7 nm. All the ANPs displayed a V-type crystalline structure and the effect of amylose chain length on crystallinity of the precipitated ANPs was negligible in the investigated range. Copyright © 2018 Elsevier Ltd. All rights reserved.

  17. Kapabilitas Pemasaran dan Operasi Serta Pengaruhnya Pada Supply Chain Management dan Kinerja Perusahaan

    Directory of Open Access Journals (Sweden)

    Hadi Purnomo

    2016-06-01

    Full Text Available Competition is a fact that needs to be faced by companies, and competitive advantage is thecore of the company’s success. To face the competition, the accuracy of the strategy undertaken by a company is one of the key success factors of the company. The strategy is to focus on the important factors that affect the performance of the company. In this case, two functions that are key to the creation of value-added are marketing and operations functions. Operations and marketing capabilities are important factors to obtain superior performance. Integration of marketing and operations (operation capabilities, marketing capabilities is believed to be a synergy to achieve the company's competitive advantage.On the other hand, Supply Chain Management (SCM is a key strategic factor to improve the company effectiveness. While an effective supply chain process is based on cross-functional collaboration of the company including operations and marketing capabilities. Thus, the main concern of this study is to focus on the influence of operationand marketing capabilities in supply chain integration and the firm performance, as well as the effect of supply chain integration on the firm performance. The results of this study based on regression analysis show that the regression coefficient of each independent variable on the dependent variable is positive. This means that the marketing and operation capabilities have positive effects on the firm performance, as well as having a positive impact on the supply chain integration. On the other side, the supply chain integration also has a positive effect on the firm performance.

  18. Lean and agile supply chain management concepts in the aspect of risk management

    Directory of Open Access Journals (Sweden)

    2010-12-01

    Full Text Available Lean and agile supply chain managements, as well as the hybrid forms (leagile supply chains, are popular and relatively widely discussed in literature. However, there are some disputes concerning differentiating these types of the management from tools and instruments such as outsourcing, single sourcing, quick response, standardizing principles and postponement. The above-mentioned concepts are discussed in a positive light as tools for achieving a competitive advantage of supply chains. A recently introduced term SCRM (Supply Chain Risk Management emphasizes the importance of the risk management in supply chains also due to the ability to achieve a competitive advantage of those chains in which a risk is identified, estimated, managed and controlled. Therefore, it seems to be of benefit to look for the relationships and dependencies between these concepts (some references were made to the author's own research. A significant part of the papers concerns the identification of risks related to the above-mentioned instruments of supply chain management. However, the concepts of lean and agile management are often discussed due to the fundamental determiners of the functioning of a supply chain such as the nature of the demand, the character of goods and the total lead-time. According to the author, the discussed concepts could be viewed concerning supply chain risk management. It could facilitate the choice of a supply chain strategy based on the risk analysis. Several case studies were included to support the presented considerations.

  19. Cloning and molecular characterization of the cDNAs encoding the variable regions of an anti-CD20 monoclonal antibody.

    Science.gov (United States)

    Shanehbandi, Dariush; Majidi, Jafar; Kazemi, Tohid; Baradaran, Behzad; Aghebati-Maleki, Leili

    2017-01-01

    CD20-based targeting of B-cells in hematologic malignancies and autoimmune disorders is associated with outstanding clinical outcomes. Isolation and characterization of VH and VL cDNAs encoding the variable regions of the heavy and light chains of monoclonal antibodies (MAb) is necessary to produce next generation MAbs and their derivatives such as bispecific antibodies (bsAb) and single-chain variable fragments (scFv). This study was aimed at cloning and characterization of the VH and VL cDNAs from a hybridoma cell line producing an anti-CD20 MAb. VH and VL fragments were amplified, cloned and characterized. Furthermore, amino acid sequences of VH, VL and corresponding complementarity-determining regions (CDR) were determined and compared with those of four approved MAbs including Rituximab (RTX), Ibritumomab tiuxetan, Ofatumumab and GA101. The cloned VH and VL cDNAs were found to be functional and follow a consensus pattern. Amino acid sequences corresponding to the VH and VL fragments also indicated noticeable homologies to those of RTX and Ibritumomab. Furthermore, amino acid sequences of the relating CDRs had remarkable similarities to their counterparts in RTX and Ibritumomab. Successful recovery of VH and VL fragments encourages the development of novel CD20 targeting bsAbs, scFvs, antibody conjugates and T-cells armed with chimeric antigen receptors.

  20. Revealing the Supramolecular Nature of Side-Chain Terpyridine-Functionalized Polymer Networks

    Directory of Open Access Journals (Sweden)

    Jérémy Brassinne

    2015-01-01

    Full Text Available Nowadays, finely controlling the mechanical properties of polymeric materials is possible by incorporating supramolecular motifs into their architecture. In this context, the synthesis of a side-chain terpyridine-functionalized poly(2-(dimethylaminoethyl methacrylate is reported via reversible addition-fragmentation chain transfer polymerization. By addition of transition metal ions, concentrated aqueous solutions of this polymer turn into metallo-supramolecular hydrogels whose dynamic mechanical properties are investigated by rotational rheometry. Hence, the possibility for the material to relax mechanical constrains via dissociation of transient cross-links is brought into light. In addition, the complex phenomena occurring under large oscillatory shear are interpreted in the context of transient networks.