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.

Serum Free Light Chains

Science.gov (United States)

... 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 ...

Structure of single-chain single crystals of isotactic polystyrene and their radiation resistance

International Nuclear Information System (INIS)

Bu Haishan; Cao Jie; Xu Shengyong; Zhang Ze

1997-01-01

The structure of the single-chain single crystals of isotactic polystyrene (i-PS) was investigated by electron diffraction (ED) and high resolution electron microscopy (HREM). The nano-scale single-chain single crystals were found to be very stable to electron irradiation. According to the unit cell of i-PS crystals, the reflection rings in ED pattern and the lattice fringes in HREM images could be indexed, but the lower-index diffractions were not found. It is proposed that the single-chain single crystals are very small, thus secondary electrons may be allowed to escape and radiation damage is highly reduced, and that there are less lower-index lattice planes in the single-chain single crystals to provide sufficient diffraction intensity for recording. HREM images can be achieved at room temperature in the case of single-chain single crystals because of its stability to electron irradiation, therefore, this might be a novel experimental approach to the study of crystal structure of macromolecules

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+

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)

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.

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

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.

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.

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

Single-Chain Folding of Synthetic Polymers: A Critical Update.

Science.gov (United States)

Altintas, Ozcan; Barner-Kowollik, Christopher

2015-11-23

The current contribution serves as a critical update to a previous feature article from us (Macromol. Rapid Commun. 2012, 33, 958-971), and highlights the latest advances in the preparation of single chain polymeric nanoparticles and initial-yet promising-attempts towards mimicking the structure of natural biomacromolecules via single-chain folding of well-defined linear polymers via so-called single chain selective point folding and repeat unit folding. The contribution covers selected examples from the literature published up to ca. September 2015. Our aim is not to provide an exhaustive review but rather highlight a selection of new and exciting examples for single-chain folding based on advanced macromolecular precision chemistry. Initially, the discussion focuses on the synthesis and characterization of single-chain folded structures via selective point folding. The second part of the feature article addresses the folding of well-defined single-chain polymers by means of repeat unit folding. The current state of the art in the field of single-chain folding indicates that repeat unit folding-driven nanoparticle preparation is well-advanced, while initial encouraging steps towards building selective point folding systems have been taken. In addition, a summary of the-in our view-open key questions is provided that may guide future biomimetic design efforts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

Stable single helical C- and I-chains inside single-walled carbon nanotubes

International Nuclear Information System (INIS)

Yao Z; Li Y; Jing X D; Meng F S; Zhao X; Li J H; Qiu Z Y; Yuan Q; Wang W X; Bi L; Liu H; Zhang Y P; Liu C J; Zheng S P; Liu B B

2016-01-01

The helicity of stable single helical carbon chains and iodine chains inside single-walled carbon nanotubes (SWCNTs) is studied by calculating the systematic van der Waals interaction energy. The results show that the optimal helical radius increases linearly with increasing tube radius, which produces a constant separation between the chain structure and the tube wall. The helical angle exhibits a ladder-like decrease with increasing tube radius, indicating that a large tube can produce a small helicity in the helical structures. (paper)

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...

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.

Optical Properties of a Single Carbon Chain-Doped Silicene Nanoribbon

Science.gov (United States)

Lu, Dao-Bang; Song, Yu-Ling; Huang, Xiao-yu; Wang, Chong

2018-05-01

Using first-principles spin polarization density function theory calculations, we have studied the electronic and optical properties of zigzag-edge silicene nanoribbons (ZSiNRs) doped with a single carbon chain. Because of the doped carbon chain, there are several defect states in the band structures of ZSiNRs across the Fermi level, and the ferromagnetic ground state is metallic. The dielectric functions in all three dimensions are completely different from each other, and thus the system exhibits strong optical anisotropism. The carbon chain influenced the dielectric functions most at low energy. The first peak in the E//x direction of the dielectric spectrum exhibits a significant blueshift, and its value has changed as well. The main absorption wavelength depends on the polarization direction of the incident light, but occurs within the UV region for all polarization directions. The peaks of the energy loss spectra correspond to the trailing edges in the reflectivity spectrum, and the highest peak corresponds to a plasmon frequency. Our results could be useful for investigating nanodevices based on silicene nanoribbons.

Novel scenario of the folding transition of a single chain

International Nuclear Information System (INIS)

Yoshikawa, Kenichi; Yoshinaga, Natsuhiko

2005-01-01

Unique characteristics of a single polymer chain with the effects of stiffness and charge are discussed. It has been well established that a flexible polymer chain undergoes a continuous transition from an elongated coil to a compact globule, corresponding to the transition between disordered gas-like and disordered liquid-like states. Here, we will show that a semiflexible chain exhibits a discrete transition from coil to compact states, corresponding to a disorder-order transition to an ordered crystalline state. We will propose a novel strategy to obtain various kinds of nano-ordered structures from single chains connecting a pair of chains of different stiffness. We will also discuss the effect of charge, putting emphasis on intramolecular segregation in a single polyelectrolyte chain

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...

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.

[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.

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

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.

Effect of Chain Conformation on the Single-Molecule Melting Force in Polymer Single Crystals: Steered Molecular Dynamics Simulations Study.

Science.gov (United States)

Feng, Wei; Wang, Zhigang; Zhang, Wenke

2017-02-28

Understanding the relationship between polymer chain conformation as well as the chain composition within the single crystal and the mechanical properties of the corresponding single polymer chain will facilitate the rational design of high performance polymer materials. Here three model systems of polymer single crystals, namely poly(ethylene oxide) (PEO), polyethylene (PE), and nylon-66 (PA66) have been chosen to study the effects of chain conformation, helical (PEO) versus planar zigzag conformation (PE, PA66), and chain composition (PE versus PA66) on the mechanical properties of a single polymer chain. To do that, steered molecular dynamics simulations were performed on those polymer single crystals by pulling individual polymer chains out of the crystals. Our results show that the patterns of force-extension curve as well as the chain moving mode are closely related to the conformation of the polymer chain in the single crystal. In addition, hydrogen bonds can enhance greatly the force required to stretch the polymer chain out of the single crystal. The dynamic breaking and reformation of multivalent hydrogen bonds have been observed for the first time in PA66 at the single molecule level.

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.

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.

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.

White Polymer Light-Emitting Diodes Based on Exciplex Electroluminescence from Polymer Blends and a Single Polymer.

Science.gov (United States)

Liang, Junfei; Zhao, Sen; Jiang, Xiao-Fang; Guo, Ting; Yip, Hin-Lap; Ying, Lei; Huang, Fei; Yang, Wei; Cao, Yong

2016-03-09

In this Article, we designed and synthesized a series of polyfluorene derivatives, which consist of the electron-rich 4,4'-(9-alkyl-carbazole-3,6-diyl)bis(N,N-diphenylaniline) (TPA-Cz) in the side chain and the electron-deficient dibenzothiophene-5,5-dioxide (SO) unit in the main chain. The resulting copolymer PF-T25 that did not comprise the SO unit exhibited blue light-emission with the Commission Internationale de L'Eclairage coordinates of (0.16, 0.10). However, by physically blending PF-T25 with a blue light-emitting SO-based oligomer, a novel low-energy emission correlated to exciplex emerged due to the appropriate energy level alignment of TPA-Cz and the SO-based oligomers, which showed extended exciton lifetime as confirmed by time-resolved photoluminescent spectroscopy. The low-energy emission was also identified in copolymers consisting of SO unit in the main chain, which can effectively compensate for the high-energy emission to produce binary white light-emission. Polymer light-emitting diodes based on the exciplex-type single greenish-white polymer exhibit the peak luminous efficiency of 2.34 cd A(-1) and the maximum brightness of 12 410 cd m(-2), with Commission Internationale de L'Eclairage color coordinates (0.27, 0.39). The device based on such polymer showed much better electroluminescent stability than those based on blending films. These observations indicated that developing a single polymer with the generated exciplex emission can be a novel and effective molecular design strategy toward highly stable and efficient white polymer light-emitting diodes.

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.

Unexpectedly normal phase behavior of single homopolymer chains

International Nuclear Information System (INIS)

Paul, W.; Strauch, T.; Rampf, F.; Binder, K.

2007-01-01

Employing Monte Carlo simulations, we show that the topology of the phase diagram of a single flexible homopolymer chain changes in dependence on the range of an attractive square well interaction between the monomers. For a range of attraction larger than a critical value, the equilibrium phase diagram of the single polymer chain and the corresponding polymer solution phase diagram exhibit vapor (swollen coil, dilute solution), liquid (collapsed globule, dense solution), and solid phases. Otherwise, the liquid-vapor transition vanishes from the equilibrium phase diagram for both the single chain and the polymer solution. This change in topology of the phase diagram resembles the behavior known for colloidal dispersions. The interplay of enthalpy and conformational entropy in the polymer case thus can lead to the same topology of phase diagrams as the interplay of enthalpy and translational entropy in simple liquids

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.

Domain walls in single-chain magnets

Science.gov (United States)

Pianet, Vivien; Urdampilleta, Matias; Colin, Thierry; Clérac, Rodolphe; Coulon, Claude

2017-12-01

The topology and creation energy of domain walls in different magnetic chains (called Single-Chain Magnets or SCMs) are discussed. As these domain walls, that can be seen as "defects", are known to control both static and dynamic properties of these one-dimensional systems, their study and understanding are necessary first steps before a deeper discussion of the SCM properties at finite temperature. The starting point of the paper is the simple regular ferromagnetic chain for which the characteristics of the domain walls are well known. Then two cases will be discussed (i) the "mixed chains" in which isotropic and anisotropic classical spins alternate, and (ii) the so-called "canted chains" where two different easy axis directions are present. In particular, we show that "strictly narrow" domain walls no longer exist in these more complex cases, while a cascade of phase transitions is found for canted chains as the canting angle approaches 45∘. The consequence for thermodynamic properties is briefly discussed in the last part of the paper.

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.

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.)

Light chain (AL amyloidosis: update on diagnosis and management

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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.

Safety, efficacy and pharmacokinetics of rVIII-SingleChain in children with severe hemophilia A: results of a multicenter clinical trial.

Science.gov (United States)

Stasyshyn, O; Djambas Khayat, C; Iosava, G; Ong, J; Abdul Karim, F; Fischer, K; Veldman, A; Blackman, N; St Ledger, K; Pabinger, I

2017-04-01

Essentials rVIII-SingleChain is a novel recombinant factor VIII with covalently bonded heavy and light chains. Efficacy, safety and pharmacokinetics were studied in pediatric patients with severe hemophilia A. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00. rVIII-SingleChain showed excellent hemostatic efficacy and a favorable safety profile. Background rVIII-SingleChain is a novel B-domain truncated recombinant factor VIII (rFVIII) comprised of covalently bonded FVIII heavy and light chains, demonstrating a high binding affinity to von Willebrand factor. Objectives This phase III study investigated the safety, efficacy and pharmacokinetics of rVIII-SingleChain in previously treated pediatric patients hemophilia A. Patients/Methods Patients could be assigned to prophylaxis or on-demand therapy by the investigator. For patients assigned to prophylaxis, the treatment regimen and dose were based on the bleeding phenotype. For patients receiving on-demand therapy, dosing was guided by World Federation of Hemophilia recommendations. The primary endpoint was treatment success, defined as a rating of 'excellent' or 'good' on the investigator's clinical assessment of hemostatic efficacy for all treated bleeding events. Results The study enrolled 84 patients (0 to 50 EDs. In the 347 bleeds treated and evaluated by the investigator, hemostatic efficacy was rated as excellent or good in 96.3%. The median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.00, 2.20), and the median annualized bleeding rate was 3.69 (Q1, Q3: 0.00, 7.20) across all prophylaxis regimens. No participant developed an inhibitor. Conclusions rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy and a favorable safety profile in a clinical study in children hemophilia A. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and

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.

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....

Single-ion and single-chain magnetism in triangular spin-chain oxides

Science.gov (United States)

Seikh, Md. Motin; Caignaert, Vincent; Perez, Olivier; Raveau, Bernard; Hardy, Vincent

2017-05-01

S r4 -xC axM n2Co O9 oxides (x =0 and x =2 ) are found to exhibit magnetic responses typical of single-chain magnets (SCMs) and single-ion magnets (SIMs), two features generally investigated in coordination polymers or complexes. The compound x =0 appears to be a genuine SCM, in that blocking effects associated with slow spin dynamics yield remanence and coercivity in the absence of long-range ordering (LRO). In addition, SIM signatures of nearly identical nature are detected in both compounds, coexisting with SCM in x =0 and with LRO in x =2 . It is also observed that a SCM response can be recovered in x =2 after application of magnetic field. These results suggest that purely inorganic systems could play a valuable role in the topical issue of the interplay among SIM, SCM, and LRO phenomena in low-dimensional magnetism.

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.

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

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

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.

Light Chain Amyloid Fibrils Cause Metabolic Dysfunction in Human Cardiomyocytes.

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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.

Elementary excitations in single-chain magnets

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Lutz, Philipp; Aguilà, David; Mondal, Abhishake; Pinkowicz, Dawid; Marx, Raphael; Neugebauer, Petr; Fâk, Björn; Ollivier, Jacques; Clérac, Rodolphe; van Slageren, Joris

2017-09-01

Single-chain magnets (SCMs) are one-dimensional coordination polymers or spin chains that display slow relaxation of the magnetization. Typically their static magnetic properties are described by the Heisenberg model, while the description of their dynamic magnetic properties is based on an Ising-like model. The types of excitations predicted by these models (collective vs localized) are quite different. Therefore we probed the nature of the elementary excitations for two SCMs abbreviated Mn2Ni and Mn2Fe , as well as a mononuclear derivative of the Mn2Fe chain, by means of high-frequency electron paramagnetic resonance spectroscopy (HFEPR) and inelastic neutron scattering (INS). We find that the HFEPR spectra of the chains are clearly distinct from those of the monomer. The momentum transfer dependence of the INS intensity did not reveal significant dispersion, indicating an essentially localized nature of the excitations. At the lowest temperatures these are modified by the occurrence of short-range correlations.

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.

Development of two dimensional electrophoresis method using single chain DNA

International Nuclear Information System (INIS)

Ikeda, Junichi; Hidaka, So

1998-01-01

By combining a separation method due to molecular weight and a method to distinguish difference of mono-bases, it was aimed to develop a two dimensional single chain DNA labeled with Radioisotope (RI). From electrophoretic pattern difference of parent and variant strands, it was investigated to isolate the root module implantation control gene. At first, a Single Strand Conformation Polymorphism (SSCP) method using concentration gradient gel was investigated. As a result, it was formed that intervals between double chain and single chain DNAs expanded, but intervals of both single chain DNAs did not expand. On next, combination of non-modified acrylic amide electrophoresis method and Denaturing Gradient-Gel Electrophoresis (DGGE) method was examined. As a result, hybrid DNA developed by two dimensional electrophoresis arranged on two lines. But, among them a band of DNA modified by high concentration of urea could not be found. Therefore, in this fiscal year's experiments, no preferable result could be obtained. By the used method, it was thought to be impossible to detect the differences. (G.K.)

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). ...

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...

Thermal Stability Threshold for Amyloid Formation in Light Chain Amyloidosis

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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.

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....

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.

Single-copy entanglement in critical quantum spin chains

International Nuclear Information System (INIS)

Eisert, J.; Cramer, M.

2005-01-01

We consider the single-copy entanglement as a quantity to assess quantum correlations in the ground state in quantum many-body systems. We show for a large class of models that already on the level of single specimens of spin chains, criticality is accompanied with the possibility of distilling a maximally entangled state of arbitrary dimension from a sufficiently large block deterministically, with local operations and classical communication. These analytical results--which refine previous results on the divergence of block entropy as the rate at which maximally entangled pairs can be distilled from many identically prepared chains--are made quantitative for general isotropic translationally invariant spin chains that can be mapped onto a quasifree fermionic system, and for the anisotropic XY model. For the XX model, we provide the asymptotic scaling of ∼(1/6)log 2 (L), and contrast it with the block entropy

Unconventional phase transitions in a constrained single polymer chain

International Nuclear Information System (INIS)

Klushin, L I; Skvortsov, A M

2011-01-01

Phase transitions were recognized among the most fascinating phenomena in physics. Exactly solved models are especially important in the theory of phase transitions. A number of exactly solved models of phase transitions in a single polymer chain are discussed in this review. These are three models demonstrating the second order phase transitions with some unusual features: two-dimensional model of β-structure formation, the model of coil–globule transition and adsorption of a polymer chain grafted on the solid surface. We also discuss models with first order phase transitions in a single macromolecule which admit not only exact analytical solutions for the partition function with explicit finite-size effects but also the non-equilibrium free energy as a function of the order parameter (Landau function) in closed analytical form. One of them is a model of mechanical desorption of a macromolecule, which demonstrates an unusual first order phase transition with phase coexistence within a single chain. Features of first and second order transitions become mixed here due to phase coexistence which is not accompanied by additional interfacial free energy. Apart from that, there exist several single-chain models belonging to the same class (adsorption of a polymer chain tethered near the solid surface or liquid–liquid interface, and escape transition upon compressing a polymer between small pistons) that represent examples of a highly unconventional first order phase transition with several inter-related unusual features: no simultaneous phase coexistence, and hence no phase boundary, non-concave thermodynamic potential and non-equivalence of conjugate ensembles. An analysis of complex zeros of partition functions upon approaching the thermodynamic limit is presented for models with and without phase coexistence. (topical review)

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

Screened ion-ion interaction in mercury-chain compounds: Single chain

International Nuclear Information System (INIS)

Mohan, M.M.; Griffin, A.

1985-01-01

At room temperature, the mercury chains in Hg/sub 3-delta/AsF 6 exhibit phonons characteristic of a one-dimensional lattice. We calculate the screening of the Hg ion-ion interaction in a single chain by electrons moving in a cylindrical potential of finite radius, within the random-phase approximation. The resulting Bohm-Staver-type expression for the phonon velocity is (Z 2 mN/sub I//MN/sub e/)/sup 1/2/v/sub F/, where Z is the Hg ionic charge and N/sub I/ (N/sub e/) is the number of ions (electrons) per unit length. Use of the Tomonaga-Luttinger solution for the electronic response function (keeping only the small-momentum scattering processes) just renormalizes the Fermi velocity in this expression

Equivalence of chain conformations in the surface region of a polymer melt and a single Gaussian chain under critical conditions.

Science.gov (United States)

Skvortsov, A M; Leermakers, F A M; Fleer, G J

2013-08-07

In the melt polymer conformations are nearly ideal according to Flory's ideality hypothesis. Silberberg generalized this statement for chains in the interfacial region. We check the Silberberg argument by analyzing the conformations of a probe chain end-grafted at a solid surface in a sea of floating free chains of concentration φ by the self-consistent field (SCF) method. Apart from the grafting, probe chain and floating chains are identical. Most of the results were obtained for a standard SCF model with freely jointed chains on a six-choice lattice, where immediate step reversals are allowed. A few data were generated for a five-choice lattice, where such step reversals are forbidden. These coarse-grained models describe the equilibrium properties of flexible atactic polymer chains at the scale of the segment length. The concentration was varied over the whole range from φ = 0 (single grafted chain) to φ = 1 (probe chain in the melt). The number of contacts with the surface, average height of the free end and its dispersion, average loop and train length, tail size distribution, end-point and overall segment distributions were calculated for a grafted probe chain as a function of φ, for several chain lengths and substrate∕polymer interactions, which were varied from strong repulsion to strong adsorption. The computations show that the conformations of the probe chain in the melt do not depend on substrate∕polymer interactions and are very similar to the conformations of a single end-grafted chain under critical conditions, and can thus be described analytically. When the substrate∕polymer interaction is fixed at the value corresponding to critical conditions, all equilibrium properties of a probe chain are independent of φ, over the whole range from a dilute solution to the melt. We believe that the conformations of all flexible chains in the surface region of the melt are close to those of an appropriate single chain in critical conditions, provided

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

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...

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.

Effect of chain stiffness on the structure of single-chain polymer nanoparticles

Science.gov (United States)

Moreno, Angel J.; Bacova, Petra; Lo Verso, Federica; Arbe, Arantxa; Colmenero, Juan; Pomposo, José A.

2018-01-01

Polymeric single-chain nanoparticles (SCNPs) are soft nano-objects synthesized by purely intramolecular cross-linking of single polymer chains. By means of computer simulations, we investigate the conformational properties of SCNPs as a function of the bending stiffness of their linear polymer precursors. We investigate a broad range of characteristic ratios from the fully flexible case to those typical of bulky synthetic polymers. Increasing stiffness hinders bonding of groups separated by short contour distances and increases looping over longer distances, leading to more compact nanoparticles with a structure of highly interconnected loops. This feature is reflected in a crossover in the scaling behaviour of several structural observables. The scaling exponents change from those characteristic for Gaussian chains or rings in θ-solvents in the fully flexible limit, to values resembling fractal or ‘crumpled’ globular behaviour for very stiff SCNPs. We characterize domains in the SCNPs. These are weakly deformable regions that can be seen as disordered analogues of domains in disordered proteins. Increasing stiffness leads to bigger and less deformable domains. Surprisingly, the scaling behaviour of the domains is in all cases similar to that of Gaussian chains or rings, irrespective of the stiffness and degree of cross-linking. It is the spatial arrangement of the domains which determines the global structure of the SCNP (sparse Gaussian-like object or crumpled globule). Since intramolecular stiffness can be varied through the specific chemistry of the precursor or by introducing bulky side groups in its backbone, our results propose a new strategy to tune the global structure of SCNPs.

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...

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...

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

Science.gov (United States)

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

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....

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.

Mechanics of biopolymer materials: Single chains to bulk properties

NARCIS (Netherlands)

Amuasi, H.E.; Storm, C.

2010-01-01

We outline the first stages in the multiscale modeling of biopolymer materials, starting with the statistical mechanics of single stiff chains. In the first coarse graining step, we demonstrate how to integrate out the single polymer degrees of freedom in supramolecular assemblies of such

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

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.

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.

Efficacy and safety of rVIII-SingleChain: results of a phase 1/3 multicenter clinical trial in severe hemophilia A

Science.gov (United States)

Mahlangu, Johnny; Kuliczkowski, Kazimierz; Karim, Faraizah Abdul; Stasyshyn, Oleksandra; Kosinova, Marina V.; Lepatan, Lynda Mae; Skotnicki, Aleksander; Boggio, Lisa N.; Klamroth, Robert; Oldenburg, Johannes; Hellmann, Andrzej; Santagostino, Elena; Baker, Ross I.; Fischer, Kathelijn; Gill, Joan C.; P’Ng, Stephanie; Chowdary, Pratima; Escobar, Miguel A.; Khayat, Claudia Djambas; Rusen, Luminita; Bensen-Kennedy, Debra; Blackman, Nicole; Limsakun, Tharin; Veldman, Alex; St. Ledger, Katie

2016-01-01

Recombinant VIII (rVIII)-SingleChain is a novel B-domain–truncated recombinant factor VIII (rFVIII), comprised of covalently bonded factor VIII (FVIII) heavy and light chains. It was designed to have a higher binding affinity for von Willebrand factor (VWF). This phase 1/3 study investigated the efficacy and safety of rVIII-SingleChain in the treatment of bleeding episodes, routine prophylaxis, and surgical prophylaxis. Participants were ≥12 years of age, with severe hemophilia A (endogenous FVIII <1%). The participants were allocated by the investigator to receive rVIII-SingleChain in either an on-demand or prophylaxis regimen. Of the 175 patients meeting study eligibility criteria, 173 were treated with rVIII-SingleChain, prophylactically (N = 146) or on-demand (N = 27). The total cumulative exposure was 14 306 exposure days (EDs), with 120 participants reaching ≥50 EDs and 52 participants having ≥100 EDs. Hemostatic efficacy was rated by the investigator as excellent or good in 93.8% of the 835 bleeds treated and assessed. Across all prophylaxis regimens, the median annualized spontaneous bleeding rate was 0.00 (Q1, Q3: 0.0, 2.4) and the median overall annualized bleeding rate (ABR) was 1.14 (Q1, Q3: 0.0, 4.2). Surgical hemostasis was rated as excellent/good in 100% of major surgeries by the investigator. No participant developed FVIII inhibitors. In conclusion, rVIII-SingleChain is a novel rFVIII molecule showing excellent hemostatic efficacy in surgery and in the control of bleeding events, low ABR in patients on prophylaxis, and a favorable safety profile in this large clinical study. This trial was registered at www.clinicaltrials.gov as #NCT01486927. PMID:27330001

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.

Selection rules for single-chain-magnet behaviour in non-collinear Ising systems

International Nuclear Information System (INIS)

Vindigni, Alessandro; Pini, Maria Gloria

2009-01-01

The magnetic behaviour of molecular single-chain magnets is investigated in the framework of a one-dimensional Ising model with single spin-flip Glauber dynamics. Opportune modifications to the original theory are required in order to account for non-collinearity of local anisotropy axes between themselves and with respect to the crystallographic (laboratory) frame. The extension of Glauber's theory to the case of a collinear Ising ferrimagnetic chain is also discussed. Within this formalism, both the dynamics of magnetization reversal in zero field and the response of the system to a weak magnetic field, oscillating in time, are studied. Depending on the experimental geometry, selection rules are found for the occurrence of slow relaxation of the magnetization at low temperatures, as well as for resonant behaviour of the a.c. susceptibility as a function of temperature at low frequencies. The present theory applies successfully to some real systems, namely Mn-, Dy- and Co-based molecular magnetic chains, showing that single-chain-magnet behaviour is not only a feature of collinear ferro- and ferrimagnetic, but also of canted antiferromagnetic chains.

Selection rules for single-chain-magnet behaviour in non-collinear Ising systems

Energy Technology Data Exchange (ETDEWEB)

Vindigni, Alessandro [Laboratorium fuer Festkoerperphysik, ETH Zuerich, CH-8093 Zuerich (Switzerland); Pini, Maria Gloria [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, Via Madonna del Piano 10, I-50019 Sesto Fiorentino (Italy)], E-mail: vindigni@phys.ethz.ch

2009-06-10

The magnetic behaviour of molecular single-chain magnets is investigated in the framework of a one-dimensional Ising model with single spin-flip Glauber dynamics. Opportune modifications to the original theory are required in order to account for non-collinearity of local anisotropy axes between themselves and with respect to the crystallographic (laboratory) frame. The extension of Glauber's theory to the case of a collinear Ising ferrimagnetic chain is also discussed. Within this formalism, both the dynamics of magnetization reversal in zero field and the response of the system to a weak magnetic field, oscillating in time, are studied. Depending on the experimental geometry, selection rules are found for the occurrence of slow relaxation of the magnetization at low temperatures, as well as for resonant behaviour of the a.c. susceptibility as a function of temperature at low frequencies. The present theory applies successfully to some real systems, namely Mn-, Dy- and Co-based molecular magnetic chains, showing that single-chain-magnet behaviour is not only a feature of collinear ferro- and ferrimagnetic, but also of canted antiferromagnetic chains.

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.

Covalent bond force profile and cleavage in a single polymer chain

Science.gov (United States)

Garnier, Lionel; Gauthier-Manuel, Bernard; van der Vegte, Eric W.; Snijders, Jaap; Hadziioannou, Georges

2000-08-01

We present here the measurement of the single-polymer entropic elasticity and the single covalent bond force profile, probed with two types of atomic force microscopes (AFM) on a synthetic polymer molecule: polymethacrylic acid in water. The conventional AFM allowed us to distinguish two types of interactions present in this system when doing force spectroscopic measurements: the first interaction is associated with adsorption sites of the polymer chains onto a bare gold surface, the second interaction is directly correlated to the rupture process of a single covalent bond. All these bridging interactions allowed us to stretch the single polymer chain and to determine the various factors playing a role in the elasticity of these molecules. To obtain a closer insight into the bond rupture process, we moved to a force sensor stable in position when measuring attractive forces. By optimizing the polymer length so as to fulfill the elastic stability conditions, we were able for the first time to map out the entire force profile associated with the cleavage of a single covalent bond. Experimental data coupled with molecular quantum mechanical calculations strongly suggest that the breaking bond is located at one end of the polymer chain.

Real-time observation of conformational switching in single conjugated polymer chains.

Science.gov (United States)

Tenopala-Carmona, Francisco; Fronk, Stephanie; Bazan, Guillermo C; Samuel, Ifor D W; Penedo, J Carlos

2018-02-01

Conjugated polymers (CPs) are an important class of organic semiconductors that combine novel optoelectronic properties with simple processing from organic solvents. It is important to study CP conformation in solution to understand the physics of these materials and because it affects the properties of solution-processed films. Single-molecule techniques are unique in their ability to extract information on a chain-to-chain basis; however, in the context of CPs, technical challenges have limited their general application to host matrices or semiliquid environments that constrain the conformational dynamics of the polymer. We introduce a conceptually different methodology that enables measurements in organic solvents using the single-end anchoring of polymer chains to avoid diffusion while preserving polymer flexibility. We explore the effect of organic solvents and show that, in addition to chain-to-chain conformational heterogeneity, collapsed and extended polymer segments can coexist within the same chain. The technique enables real-time solvent-exchange measurements, which show that anchored CP chains respond to sudden changes in solvent conditions on a subsecond time scale. Our results give an unprecedented glimpse into the mechanism of solvent-induced reorganization of CPs and can be expected to lead to a new range of techniques to investigate and conformationally manipulate CPs.

Quantum Heisenberg antiferromagnetic chains with exchange and single-ion anisotropies

International Nuclear Information System (INIS)

Peters, D; Selke, W; McCulloch, I P

2010-01-01

Using density matrix renormalization group calculations, ground state properties of the spin-1 Heisenberg chain with exchange and quadratic single-ion anisotropies in an external field are studied, for special choices of the two kinds of anisotropies. In particular, the phase diagram includes antiferromagnetic, spin-liquid (or spin-flop), IS2, and supersolid (or biconical) phases. Especially, new features of the spin-liquid and supersolid phases are discussed. Properties of the quantum chains are compared to those of corresponding classical spin chains.

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,

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.

Pressure effects on single chain magnets

Energy Technology Data Exchange (ETDEWEB)

Mito, M. E-mail: mitoh@elcs.kyutech.ac.jp; Shindo, N.; Tajiri, T.; Deguchi, H.; Takagi, S.; Miyasaka, H.; Yamashita, M.; Clerac, R.; Coulon, C

2004-05-01

Pressure effects on a single chain magnet [Mn{sub 2}(saltmen){sub 2}Ni(pao){sub 2}(py){sub 2}](ClO{sub 4}){sub 2} (saltmen{sup 2-}=N,N'-(1,1,2,2-tetramethylethylene)bis(salicylideneiminate), and pao{sup -}=pyridine-2-aldoximate) have been investigated through AC magnetic measurements under pressure (P). The slow relaxation of the magnetization depends on pressure. Both the blocking temperature (T{sub B}) and energy barrier ({delta}) increase by pressurization, and those enhancements saturate at around P=7 kbar.

Stereoelectronic Effect-Induced Conductance Switching in Aromatic Chain Single-Molecule Junctions.

Science.gov (United States)

Xin, Na; Wang, Jinying; Jia, Chuancheng; Liu, Zitong; Zhang, Xisha; Yu, Chenmin; Li, Mingliang; Wang, Shuopei; Gong, Yao; Sun, Hantao; Zhang, Guanxin; Liu, Zhirong; Zhang, Guangyu; Liao, Jianhui; Zhang, Deqing; Guo, Xuefeng

2017-02-08

Biphenyl, as the elementary unit of organic functional materials, has been widely used in electronic and optoelectronic devices. However, over decades little has been fundamentally understood regarding how the intramolecular conformation of biphenyl dynamically affects its transport properties at the single-molecule level. Here, we establish the stereoelectronic effect of biphenyl on its electrical conductance based on the platform of graphene-molecule single-molecule junctions, where a specifically designed hexaphenyl aromatic chain molecule is covalently sandwiched between nanogapped graphene point contacts to create stable single-molecule junctions. Both theoretical and temperature-dependent experimental results consistently demonstrate that phenyl twisting in the aromatic chain molecule produces different microstates with different degrees of conjugation, thus leading to stochastic switching between high- and low-conductance states. These investigations offer new molecular design insights into building functional single-molecule electrical devices.

Earlinet single calculus chain: new products overview

Science.gov (United States)

D'Amico, Giuseppe; Mattis, Ina; Binietoglou, Ioannis; Baars, Holger; Mona, Lucia; Amato, Francesco; Kokkalis, Panos; Rodríguez-Gómez, Alejandro; Soupiona, Ourania; Kalliopi-Artemis, Voudouri

2018-04-01

The Single Calculus Chain (SCC) is an automatic and flexible tool to analyze raw lidar data using EARLINET quality assured retrieval algorithms. It has been already demonstrated the SCC can retrieve reliable aerosol backscatter and extinction coefficient profiles for different lidar systems. In this paper we provide an overview of new SCC products like particle linear depolarization ratio, cloud masking, aerosol layering allowing relevant improvements in the atmospheric aerosol characterization.

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.

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...

Single molecule experiments challenge the strict wave-particle dualism of light.

Science.gov (United States)

Greulich, Karl Otto

2010-01-21

Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the "single photon limit" of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. "Single photon detectors" do not meet their promise-only "photon number resolving single photon detectors" do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

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.

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.

Population pharmacokinetics of recombinant coagulation factor VIII-SingleChain in patients with severe hemophilia A.

Science.gov (United States)

Zhang, Y; Roberts, J; Tortorici, M; Veldman, A; St Ledger, K; Feussner, A; Sidhu, J

2017-06-01

Essentials rVIII-SingleChain is a unique recombinant factor VIII (FVIII) molecule. A population pharmacokinetic model was based on FVIII activity of severe hemophilia A patients. The model was used to simulate factor VIII activity-time profiles for various dosing scenarios. The model supports prolonged dosing of rVIII-SingleChain with intervals of up to twice per week. Background Single-chain recombinant coagulation factor VIII (rVIII-SingleChain) is a unique recombinant coagulation factor VIII molecule. Objectives To: (i) characterize the population pharmacokinetics (PK) of rVIII-SingleChain in patients with severe hemophilia A; (ii) identify correlates of variability in rVIII-SingleChain PK; and (iii) simulate various dosing scenarios of rVIII-SingleChain. Patients/Methods A population PK model was developed, based on FVIII activity levels of 130 patients with severe hemophilia A (n = 91 for ≥ 12-65 years; n = 39 for  85% and > 93% of patients were predicted to maintain FVIII activity level above 1 IU dL -1 , at all times with three-times-weekly dosing (given on days 0, 2, and 4.5) at the lowest (20 IU kg -1 ) and highest (50 IU kg -1 ) doses, respectively. For twice weekly dosing (days 0 and 3.5) of 50 IU kg -1 rVIII-SingleChain, 62-80% of patients across all ages were predicted to maintain a FVIII activity level above 1 IU dL -1 at day 7. Conclusions The population PK model adequately characterized rVIII-SingleChain PK, and the model can be utilized to simulate FVIII activity-time profiles for various dosing scenarios. © 2017 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis.

Single-molecule exploration of photoprotective mechanisms in light-harvesting complexes

Science.gov (United States)

Yang, Hsiang-Yu; Schlau-Cohen, Gabriela S.; Gwizdala, Michal; Krüger, Tjaart; Xu, Pengqi; Croce, Roberta; van Grondelle, Rienk; Moerner, W. E.

2015-03-01

Plants harvest sunlight by converting light energy to electron flow through the primary events in photosynthesis. One important question is how the light harvesting machinery adapts to fluctuating sunlight intensity. As a result of various regulatory processes, efficient light harvesting and photoprotection are balanced. Some of the biological steps in the photoprotective processes have been extensively studied and physiological regulatory factors have been identified. For example, the effect of lumen pH in changing carotenoid composition has been explored. However, the importance of photophysical dynamics in the initial light-harvesting steps and its relation to photoprotection remain poorly understood. Conformational and excited-state dynamics of multi-chromophore pigment-protein complexes are often difficult to study and limited information can be extracted from ensemble-averaged measurements. To address the problem, we use the Anti-Brownian ELectrokinetic (ABEL) trap to investigate the fluorescence from individual copies of light-harvesting complex II (LHCII), the primary antenna protein in higher plants, in a solution-phase environment. Perturbative surface immobilization or encapsulation schemes are avoided, and therefore the intrinsic dynamics and heterogeneity in the fluorescence of individual proteins are revealed. We perform simultaneous measurements of fluorescence intensity (brightness), excited-state lifetime, and emission spectrum of single trapped proteins. By analyzing the correlated changes between these observables, we identify forms of LHCII with different fluorescence intensities and excited-state lifetimes. The distinct forms may be associated with different energy dissipation mechanisms in the energy transfer chain. Changes of relative populations in response to pH and carotenoid composition are observed, which may extend our understanding of the molecular mechanisms of photoprotection.

Single Molecule Experiments Challenge the Strict Wave-Particle Dualism of Light

Directory of Open Access Journals (Sweden)

Karl Otto Greulich

2010-01-01

Full Text Available Single molecule techniques improve our understanding of the photon and light. If the single photon double slit experiment is performed at the “single photon limit” of a multi-atom light source, faint light pulses with more than one photon hamper the interpretation. Single molecules, quantum dots or defect centres in crystals should be used as light source. “Single photon detectors” do not meet their promise―only “photon number resolving single photon detectors” do so. Particularly, the accumulation time argument, the only safe basis for the postulate of a strictly particle like photon, has so far not yet been verified.

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

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...

Molecular dynamics simulation of AFM studies of a single polymer chain

International Nuclear Information System (INIS)

Wang Wenhai; Kistler, Kurt A.; Sadeghipour, Keya; Baran, George

2008-01-01

Single polymer chain force-extension behavior measured by Atomic Force Microscopy (AFM) was interpreted by molecular dynamics (MD) simulation performed by applying a bead-spring (coarse-graining) model in which the bond potential function between adjacent beads is described by a worm-like chain (WLC) model. Simulation results indicate that caution should be applied when interpreting experimental AFM data, because the data vary depending on the point of AFM tip-polymer chain attachment. This approach offers an effective way for eventual analysis of the mechanical behavior of complex polymer networks

Molecular dynamics simulation of AFM studies of a single polymer chain

Energy Technology Data Exchange (ETDEWEB)

Wang Wenhai [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States); Kistler, Kurt A. [Department of Chemistry, Temple University, 1901 N. 13th Street, Philadelphia, PA 19122 (United States); Sadeghipour, Keya [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States); Baran, George [Center for Bioengineering and Biomaterials, College of Engineering, Temple University, 1947 N. 12th Street, Philadelphia, PA 19122 (United States)], E-mail: grbaran@temple.edu

2008-11-24

Single polymer chain force-extension behavior measured by Atomic Force Microscopy (AFM) was interpreted by molecular dynamics (MD) simulation performed by applying a bead-spring (coarse-graining) model in which the bond potential function between adjacent beads is described by a worm-like chain (WLC) model. Simulation results indicate that caution should be applied when interpreting experimental AFM data, because the data vary depending on the point of AFM tip-polymer chain attachment. This approach offers an effective way for eventual analysis of the mechanical behavior of complex polymer networks.

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.

Single-Molecule Imaging Reveals Topology Dependent Mutual Relaxation of Polymer Chains

KAUST Repository

Abadi, Maram; Serag, Maged F.; Habuchi, Satoshi

2015-01-01

The motion and relaxation of linear and cyclic polymers under entangled conditions are investigated by means of a newly developed single-molecule tracking technique, cumulative-area (CA) tracking. CA tracking enables simultaneous quantitative characterization of the diffusion mode, diffusion rate, and relaxation time that have been impossible with a widely used conventional single-molecule localization and tracking method, by analyzing cumulative areas occupied by the moving molecule. Using the novel approach, we investigate the motion and relaxation of entangled cyclic polymers, which have been an important but poorly understood question. Fluorescently labeled 42 kbp linear or cyclic tracer dsDNAs in concentrated solutions of unlabeled linear or cyclic DNAs are used as model systems. We show that CA tracking can explicitly distinguish topology-dependent diffusion mode, rate, and relaxation time, demonstrating that the method provides an invaluable tool for characterizing topological interaction between the entangled chains. We further demonstrate that the current models proposed for the entanglement between cyclic polymers which are based on cyclic chains moving through an array of fixed obstacles cannot correctly describe the motion of the cyclic chain under the entangled conditions. Our results rather suggest the mutual relaxation of the cyclic chains, which underscore the necessity of developing a new model to describe the motion of cyclic polymer under the entangled conditions based on the mutual interaction of the chains.

Single-Molecule Imaging Reveals Topology Dependent Mutual Relaxation of Polymer Chains

KAUST Repository

Abadi, Maram

2015-08-24

The motion and relaxation of linear and cyclic polymers under entangled conditions are investigated by means of a newly developed single-molecule tracking technique, cumulative-area (CA) tracking. CA tracking enables simultaneous quantitative characterization of the diffusion mode, diffusion rate, and relaxation time that have been impossible with a widely used conventional single-molecule localization and tracking method, by analyzing cumulative areas occupied by the moving molecule. Using the novel approach, we investigate the motion and relaxation of entangled cyclic polymers, which have been an important but poorly understood question. Fluorescently labeled 42 kbp linear or cyclic tracer dsDNAs in concentrated solutions of unlabeled linear or cyclic DNAs are used as model systems. We show that CA tracking can explicitly distinguish topology-dependent diffusion mode, rate, and relaxation time, demonstrating that the method provides an invaluable tool for characterizing topological interaction between the entangled chains. We further demonstrate that the current models proposed for the entanglement between cyclic polymers which are based on cyclic chains moving through an array of fixed obstacles cannot correctly describe the motion of the cyclic chain under the entangled conditions. Our results rather suggest the mutual relaxation of the cyclic chains, which underscore the necessity of developing a new model to describe the motion of cyclic polymer under the entangled conditions based on the mutual interaction of the chains.

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.

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 ...

Light emission from organic single crystals operated by electrolyte doping

Science.gov (United States)

Matsuki, Keiichiro; Sakanoue, Tomo; Yomogida, Yohei; Hotta, Shu; Takenobu, Taishi

2018-03-01

Light-emitting devices based on electrolytes, such as light-emitting electrochemical cells (LECs) and electric double-layer transistors (EDLTs), are solution-processable devices with a very simple structure. Therefore, it is necessary to apply this device structure into highly fluorescent organic materials for future printed applications. However, owing to compatibility problems between electrolytes and organic crystals, electrolyte-based single-crystal light-emitting devices have not yet been demonstrated. Here, we report on light-emitting devices based on organic single crystals and electrolytes. As the fluorescent materials, α,ω-bis(biphenylyl)terthiophene (BP3T) and 5,6,11,12-tetraphenylnaphthacene (rubrene) single crystals were selected. Using ionic liquids as electrolytes, we observed clear light emission from BP3T LECs and rubrene EDLTs.

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 ...

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.

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.

Single-Chain Conformation for Interacting Poly(N-isopropylacrylamide in Aqueous Solution

Directory of Open Access Journals (Sweden)

Boualem Hammouda

2015-04-01

Full Text Available The demixing phase behavior of Poly(N-isopropylacrylamide (PNIPAM aqueous solution is investigated using small-angle neutron scattering. This polymer phase separates upon heating and demixes around 32 °C. The pre-transition temperature range is characterized by two scattering modes; a low-Q (large-scale signal and a high-Q dissolved chains signal. In order to get insight into this pre-transition region, especially the origin of the low-Q (large-scale structure, the zero average contrast method is used in order to isolate single-chain conformations even in the demixing polymers transition region. This method consists of measuring deuterated and non-deuterated polymers dissolved in mixtures of deuterated and non-deuterated water for which the polymer scattering length density matches the solvent scattering length density. A fixed 4% polymer mass fraction is used in a contrast variation series where the d-water/h-water fraction is varied in order to determine the match point. The zero average contrast (match point sample displays pure single-chain scattering with no interchain contributions. Our measurements prove that the large scale structure in this polymer solution is due to a transient polymer network formed through hydrophobic segment-segment interactions. Scattering intensity increases when the temperature gets close to the phase boundary. While the apparent radius of gyration increases substantially at the Lower Critical Solution Temperature (LCST transition due to strong interchain correlation, the single-chain true radius of gyration has been found to decrease slightly with temperature when approaching the transition.

Single-molecule study on polymer diffusion in a melt state: Effect of chain topology

KAUST Repository

Habuchi, Satoshi

2013-08-06

We report a new methodology for studying diffusion of individual polymer chains in a melt state, with special emphasis on the effect of chain topology. A perylene diimide fluorophore was incorporated into the linear and cyclic poly(THF)s, and real-time diffusion behavior of individual chains in a melt of linear poly(THF) was measured by means of a single-molecule fluorescence imaging technique. The combination of mean squared displacement (MSD) and cumulative distribution function (CDF) analysis demonstrated the broad distribution of diffusion coefficient of both the linear and cyclic polymer chains in the melt state. This indicates the presence of spatiotemporal heterogeneity of the polymer diffusion which occurs at much larger time and length scales than those expected from the current polymer physics theory. We further demonstrated that the cyclic chains showed marginally slower diffusion in comparison with the linear counterparts, to suggest the effective suppression of the translocation through the threading-entanglement with the linear matrix chains. This coincides with the higher activation energy for the diffusion of the cyclic chains than of the linear chains. These results suggest that the single-molecule imaging technique provides a powerful tool to analyze complicated polymer dynamics and contributes to the molecular level understanding of the chain interaction. © 2013 American Chemical Society.

Single-molecule study on polymer diffusion in a melt state: Effect of chain topology

KAUST Repository

Habuchi, Satoshi; Fujiwara, Susumu; Yamamoto, Takuya; Vá cha, Martin; Tezuka, Yasuyuki

2013-01-01

We report a new methodology for studying diffusion of individual polymer chains in a melt state, with special emphasis on the effect of chain topology. A perylene diimide fluorophore was incorporated into the linear and cyclic poly(THF)s, and real-time diffusion behavior of individual chains in a melt of linear poly(THF) was measured by means of a single-molecule fluorescence imaging technique. The combination of mean squared displacement (MSD) and cumulative distribution function (CDF) analysis demonstrated the broad distribution of diffusion coefficient of both the linear and cyclic polymer chains in the melt state. This indicates the presence of spatiotemporal heterogeneity of the polymer diffusion which occurs at much larger time and length scales than those expected from the current polymer physics theory. We further demonstrated that the cyclic chains showed marginally slower diffusion in comparison with the linear counterparts, to suggest the effective suppression of the translocation through the threading-entanglement with the linear matrix chains. This coincides with the higher activation energy for the diffusion of the cyclic chains than of the linear chains. These results suggest that the single-molecule imaging technique provides a powerful tool to analyze complicated polymer dynamics and contributes to the molecular level understanding of the chain interaction. © 2013 American Chemical Society.

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.

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.

Expression and characterization of recombinant single-chain salmon class I MHC fused with beta2-microglobulin with biological activity

DEFF Research Database (Denmark)

Zhao, Heng; Stet, René J M; Skjødt, Karsten

2008-01-01

Heterodimeric class I major histocompatibility complex (MHC) molecules consist of a putative 45-kDa heavy chain and a 12-kDa beta2-microglobulin (beta2m) light chain. The knowledge about MHC genes in Atlantic salmon accumulated during the last decade has allowed us to generate soluble and stable ...... MHC class I molecules with biological activity. We report here the use of a bacterial expression system to produce the recombinant single-chain MHC molecules based on a specific allele Sasa-UBA*0301. This particular allele was selected because previous work has shown its association...... antibodies were successfully produced against both the MHC class I heavy chain and beta(2)m, and showed binding to the recombinant molecule. The recombinant complex Sasabeta2mUBA*0301 was expressed and isolated; the production was scaled up by adjusting to its optimal conditions. Subsequently......, the recombinant proteins were purified by affinity chromatography using mAb against beta2m and alpha3. Eluates were analyzed by Western blot and refolded by the removal of denaturant. The correct folding was confirmed by measuring its binding capacity against mAb produced to recognize the native form of MHC...

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.

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...

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.

Markov chain analysis of single spin flip Ising simulations

International Nuclear Information System (INIS)

Hennecke, M.

1997-01-01

The Markov processes defined by random and loop-based schemes for single spin flip attempts in Monte Carlo simulations of the 2D Ising model are investigated, by explicitly constructing their transition matrices. Their analysis reveals that loops over all lattice sites using a Metropolis-type single spin flip probability often do not define ergodic Markov chains, and have distorted dynamical properties even if they are ergodic. The transition matrices also enable a comparison of the dynamics of random versus loop spin selection and Glauber versus Metropolis probabilities

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.

Structural and electronic properties of a single C chain doped zigzag BN nanoribbons

International Nuclear Information System (INIS)

Wu, Ping; Wang, Qianwen; Cao, Gengyu; Tang, Fuling; Huang, Min

2014-01-01

The effects of single C-chain on the stability, structural and electronic properties of zigzag BN nanoribbons (ZBNNRs) were investigated by first-principles calculations. C-chain was expected to dope at B-edge for all the ribbon widths N z considered. The band gaps of C-chain doped N z -ZBNNR are narrower than that of perfect ZBNNR due to new localized states induced by C-chain. The band gaps of N z -ZBNNR-C(n) are direct except for the case of C-chain position n=2. Band gaps of BN nanoribbons are tunable by C-chain and its position n, which may endow the potential applications of BNNR in electronics.

Well-defined single-chain polymer nanoparticles via thiol-Michael addition

NARCIS (Netherlands)

Kröger, A. Pia P.; Boonen, Roy J.E.A.; Paulusse, Jos M.J.

2017-01-01

A synthetic strategy has been developed giving facile access to well-defined single-chain polymer nanoparticles (SCNPs) from styrene-, acrylate- and methacrylate-based polymers. Random copolymers (polydispersity indices 1.10–1.15) of methyl (meth)acrylate, benzyl methacrylate or styrene containing

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.

Single-chain statistics and the upper wave-vector cutoff in polymer blends

International Nuclear Information System (INIS)

Holyst, R.; Vilgis, T.A.

1994-01-01

We derive the equation for the single-chain correlation function in polymer blends. The chains in the incompressible blend have a radius of gyration smaller than the radius of gyration for ideal chains. The chains shrink progressively as we approach the critical temperature T c . The correction responsible for shrinking is proportional to 1/ √N , where N is the polymerization index. At T=T c and for N=1000, the size of the chain has been estimated to be 10% smaller than the size of the ideal coil. The estimate relies on the appropriate cutoff. In the limit of N→∞ the chains approach the random walk limit. Additionally, we propose in this paper a self-consistent determination of the radius of gyration and the upper wave-vector cutoff. Our model is free from any divergences such as were encountered in the previous mean-field studies; we make an estimate of the chain size at the true critical temperature and not the mean-field one

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

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)

Inactivation of single-chain urokinase-type plasminogen activator by thrombin in human subjects

NARCIS (Netherlands)

Braat, E. A.; Levi, M. [=Marcel M.; Bos, R.; Haverkate, F.; Lassen, M. R.; de Maat, M. P.; Rijken, D. C.

1999-01-01

Thrombin cleaves single-chain urokinase-type plasminogen activator (scu-PA) into a virtually inactive two-chain form (tcu-PA/T), a process that may protect a blood clot from early fibrinolysis. It is not known under what circumstances tcu-PA/T can be generated in vivo. We have studied the occurrence

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)

An integrated single- and two-photon non-diffracting light-sheet microscope

Science.gov (United States)

Lau, Sze Cheung; Chiu, Hoi Chun; Zhao, Luwei; Zhao, Teng; Loy, M. M. T.; Du, Shengwang

2018-04-01

We describe a fluorescence optical microscope with both single-photon and two-photon non-diffracting light-sheet excitations for large volume imaging. With a special design to accommodate two different wavelength ranges (visible: 400-700 nm and near infrared: 800-1200 nm), we combine the line-Bessel sheet (LBS, for single-photon excitation) and the scanning Bessel beam (SBB, for two-photon excitation) light sheet together in a single microscope setup. For a transparent thin sample where the scattering can be ignored, the LBS single-photon excitation is the optimal imaging solution. When the light scattering becomes significant for a deep-cell or deep-tissue imaging, we use SBB light-sheet two-photon excitation with a longer wavelength. We achieved nearly identical lateral/axial resolution of about 350/270 nm for both imagings. This integrated light-sheet microscope may have a wide application for live-cell and live-tissue three-dimensional high-speed imaging.

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media

OpenAIRE

Gracia R.; Marradi M.; Cossío U.; Benito A.; Pérez-San Vicente A.; Gómez-Vallejo V.; Grande H.-J.; Llop J.; and Loinaz I.

2017-01-01

Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and under mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstrating their potential use as imaging contrast agents.

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....

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).

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)

Single-cell atomic quantum memory for light

International Nuclear Information System (INIS)

Opatrny, Tomas

2006-01-01

Recent experiments demonstrating atomic quantum memory for light [B. Julsgaard et al., Nature 432, 482 (2004)] involve two macroscopic samples of atoms, each with opposite spin polarization. It is shown here that a single atomic cell is enough for the memory function if the atoms are optically pumped with suitable linearly polarized light, and quadratic Zeeman shift and/or ac Stark shift are used to manipulate rotations of the quadratures. This should enhance the performance of our quantum memory devices since less resources are needed and losses of light in crossing different media boundaries are avoided

Optimization of the crystallizability of a single-chain antibody fragment

Czech Academy of Sciences Publication Activity Database

Škerlová, Jana; Král, Vlastimil; Fábry, Milan; Sedláček, Juraj; Veverka, Václav; Řezáčová, Pavlína

2014-01-01

Roč. 70, č. 12 (2014), s. 1701-1706 ISSN 1744-3091 R&D Projects: GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:68378050 Keywords : single-chain antibody fragment * Thermofluor assay * differential scanning fluorimetry * crystallizability optimization * oligomerization * crystallization Subject RIV: CE - Biochemistry Impact factor: 0.527, year: 2014

Choice between Single and Multiple Reinforcers in Concurrent-Chains Schedules

Science.gov (United States)

Mazur, James E.

2006-01-01

Pigeons responded on concurrent-chains schedules with equal variable-interval schedules as initial links. One terminal link delivered a single reinforcer after a fixed delay, and the other terminal link delivered either three or five reinforcers, each preceded by a fixed delay. Some conditions included a postreinforcer delay after the single…

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.

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

Single Atoms Preparation Using Light-Assisted Collisions

Directory of Open Access Journals (Sweden)

Yin Hsien Fung

2016-01-01

Full Text Available The detailed control achieved over single optically trapped neutral atoms makes them candidates for applications in quantum metrology and quantum information processing. The last few decades have seen different methods developed to optimize the preparation efficiency of single atoms in optical traps. Here we review the near-deterministic preparation of single atoms based on light-assisted collisions and describe how this method can be implemented in different trap regimes. The simplicity and versatility of the method makes it feasible to be employed in future quantum technologies such as a quantum logic device.

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

Strong-coupling behaviour of two t - J chains with interchain single-electron hopping

International Nuclear Information System (INIS)

Zhang Guangming; Feng Shiping; Yu Lu.

1994-01-01

Using the fermion-spin transformation to implement spin-charge separation of constrained electrons, a model of two t - J chains with interchain single-electron hopping is studied by abelian bosonization. After spin-charge decoupling the charge dynamics can be trivially solved, while the spin dynamics is determined by a strong-coupling fixed point where the correlation functions can be calculated explicitly. This is a generalization of the Luther-Emery line for two-coupled t - J chains. The interchain single-electron hopping changes the asymptotic behaviour of the interchain spin-spin correlation functions and the electron Green function, but their exponents are independent of the coupling strength. (author). 25 refs

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

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.

Dynamical behavior of a single polymer chain under nanometric confinement

Science.gov (United States)

Lagrené, K.; Zanotti, J.-M.; Daoud, M.; Farago, B.; Judeinstein, P.

2010-10-01

We address the dynamical behavior of a single polymer chain under nanometric confinement. We consider a polymer melt made of a mixture of hydrogenated and deuterated high molecular mass Poly(Ethylene Oxide) (PEO). The confining material is a membrane of Anodic Aluminum Oxide (AAO), a macroscopically highly ordered confining system made of parallel cylindrical channels. We use Neutron Spin-Echo (NSE) under the Zero Average Contrast (ZAC) condition to, all at once, i) match the intense porous AAO detrimental elastic SANS (Small Angle Neutron Scattering) contribution to the total intermediate scattering function I(Q,t) and ii) measure the Q dependence of the dynamical modes of a single chain under confinement. The polymer dynamics is probed on an extremely broad spacial ([2.2 10-2 Å-1, 0.2 Å-1]) and temporal ([0.1 ns, 600 ns]) ranges. We do not detect any influence of confinement on the polymer dynamics. This result is discussed in the framework of the debate on the existence of a "corset effect" recently suggested by NMR relaxometry data.

Interfacial free energy governs single polystyrene chain collapse in water and aqueous solutions.

Science.gov (United States)

Li, Isaac T S; Walker, Gilbert C

2010-05-12

The hydrophobic interaction is significantly responsible for driving protein folding and self-assembly. To understand it, the thermodynamics, the role of water structure, the dewetting process surrounding hydrophobes, and related aspects have undergone extensive investigations. Here, we examine the hypothesis that polymer-solvent interfacial free energy is adequate to describe the energetics of the collapse of a hydrophobic homopolymer chain at fixed temperature, which serves as a much simplified model for studying the hydrophobic collapse of a protein. This implies that changes in polymer-solvent interfacial free energy should be directly proportional to the force to extend a collapsed polymer into a bad solvent. To test this hypothesis, we undertook single-molecule force spectroscopy on a collapsed, single, polystyrene chain in water-ethanol and water-salt mixtures where we measured the monomer solvation free energy from an ensemble average conformations. Different proportions within the binary mixture were used to create solvents with different interfacial free energies with polystyrene. In these mixed solvents, we observed a linear correlation between the interfacial free energy and the force required to extend the chain into solution, which is a direct measure of the solvation free energy per monomer on a single chain at room temperature. A simple analytical model compares favorably with the experimental results. This knowledge supports a common assumption that explicit water solvent may not be necessary for cases whose primary concerns are hydrophobic interactions and hydrophobic hydration.

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.

Pricing and ordering policies for price-dependent demand in a supply chain of a single retailer and a single manufacturer

Science.gov (United States)

Kim, Jungkyu; Hong, Yushin; Kim, Taebok

2011-01-01

This article discusses joint pricing and ordering policies for price-dependent demand in a supply chain consisting of a single retailer and a single manufacturer. The retailer places orders for products according to an EOQ policy and the manufacturer produces them on a lot-for-lot basis. Four mechanisms with differing levels of coordination are presented. Mathematical models are formulated and solution procedures are developed to determine the optimal retail prices and order quantities. Through extensive numerical experiments, we analyse and compare the behaviours and characteristics of the proposed mechanisms, and find that enhancing the level of coordination has important benefits for the supply chain.

Enantiopure heterobimetallic single-chain magnets from the chiral Ru(III) building block.

Science.gov (United States)

Ru, Jing; Gao, Feng; Wu, Tao; Yao, Min-Xia; Li, Yi-Zhi; Zuo, Jing-Lin

2014-01-21

A pair of one-dimensional enantiomers based on the versatile chiral dicyanoruthenate(III) building block have been synthesized and they are chiral single-chain magnets with the effective spin-reversal barrier of 28.2 K.

Single-Molecule Light-Sheet Imaging of Suspended T Cells.

Science.gov (United States)

Ponjavic, Aleks; McColl, James; Carr, Alexander R; Santos, Ana Mafalda; Kulenkampff, Klara; Lippert, Anna; Davis, Simon J; Klenerman, David; Lee, Steven F

2018-05-08

Adaptive immune responses are initiated by triggering of the T cell receptor. Single-molecule imaging based on total internal reflection fluorescence microscopy at coverslip/basal cell interfaces is commonly used to study this process. These experiments have suggested, unexpectedly, that the diffusional behavior and organization of signaling proteins and receptors may be constrained before activation. However, it is unclear to what extent the molecular behavior and cell state is affected by the imaging conditions, i.e., by the presence of a supporting surface. In this study, we implemented single-molecule light-sheet microscopy, which enables single receptors to be directly visualized at any plane in a cell to study protein dynamics and organization in live, resting T cells. The light sheet enabled the acquisition of high-quality single-molecule fluorescence images that were comparable to those of total internal reflection fluorescence microscopy. By comparing the apical and basal surfaces of surface-contacting T cells using single-molecule light-sheet microscopy, we found that most coated-glass surfaces and supported lipid bilayers profoundly affected the diffusion of membrane proteins (T cell receptor and CD45) and that all the surfaces induced calcium influx to various degrees. Our results suggest that, when studying resting T cells, surfaces are best avoided, which we achieve here by suspending cells in agarose. Copyright © 2018. Published by Elsevier Inc.

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.

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

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.

Premenstrual mood and empathy after a single light therapy session.

Science.gov (United States)

Aan Het Rot, Marije; Miloserdov, Kristina; Buijze, Anna L F; Meesters, Ybe; Gordijn, Marijke C M

2017-10-01

To examine whether acute changes in cognitive empathy might mediate the impact of light therapy on mood, we assessed the effects of a single light-therapy session on mood and cognitive empathy in 48 premenstrual women, including 17 who met Premenstrual Symptoms Screening Tool criteria for moderate-to-severe premenstrual syndrome / premenstrual dysphoric disorder (PMS/PMDD). Using a participant-blind between-groups design, 23 women underwent 30min of morning light therapy (5,000lx; blue-enriched polychromatic light, 17,000K) while 25 women had a sham session (200lx, polychromatic light, 5,000K). We administered the Positive Affect and Negative Affect Schedule and the Affect Grid right before and after the intervention, and 60min later upon completion of a computerized empathic accuracy task. There were no significant effects of light condition on cognitive empathy as assessed using the computer task. Nonetheless, bright light reduced negative affect, specifically in women not using hormonal contraceptives. No effects of bright light on mood were observed in women who were using contraceptives. If a single light-therapy session does not alter cognitive empathy, then cognitive empathy may not mediate the impact of light therapy on mood in premenstrual women. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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

Conformation of Single Pentablock Ionomer Chains in Dilute Solutions

Energy Technology Data Exchange (ETDEWEB)

Aryal, Dipak [Clemson Univ., SC (United States); Perahia, Dvora [Clemson Univ., SC (United States); Grest, Gary S. [Sandia National Lab. (SNL-NM), Albuquerque, NM (United States)

2015-04-01

The conformation of single chain pentablock ionomers (A-B-C-B-A) containing randomly sulfonated polystyrene in the center block, tethered to poly-ethylene-r-propylene end-capped by poly-t-butyl styrene is studied in dilute solutions by molecular dynamics simulations. Multi-block copolymers offer a means to tailor several properties into one molecule, taking advantage of their rich phase diagram together with unique properties of specific blocks. For this pentablock the ionic block facilitates transport while the A and B components are incorporated for mechanical stability. The present study investigates the confirmation of a single chain of pentablock ionomer of molecular weight M_w ~ 50,000 g/mol and sulfonated polystyrene of the same molecular weight as that of the center block for six sulfonation fractions f from f=0.0-0.55. For the sulfonated systems Na⁺ counterions are included. Results for the equilibrium conformation of the chains and the three blocks in water and 1:1 mixture of cyclohexane and n-heptane are compared to simulations in implicit poor solvents with dielectric constants ε =1.0 and 77.73. In water, the pentablock is collapsed with sulfonated groups on the outer surface. As the sulfonation fraction f increases, the ionic, center block is increasingly segregated from the hydrophobic regions. In the 1:1 mixture of cyclohexane and heptane both the flexible and end blocks are swollen while the center ionic block is collasped for f>0, while for f=0 all blocks are swollen. In both implicit poor solvents the pentablock is collapsed into a nearly spherical shape for all f. The sodium counterions are dispersed widely throughout the simulation cell for both water and ε =77.73 whereas for ε =1.0 the counterions are largely condensed on the collapsed pentablock.

Single particle analysis with a 3600 light scattering photometer

International Nuclear Information System (INIS)

Bartholdi, M.F.

1979-06-01

Light scattering by single spherical homogeneous particles in the diameter range 1 to 20 μm and relative refractive index 1.20 is measured. Particle size of narrowly dispersed populations is determined and a multi-modal dispersion of five components is completely analyzed. A 360 0 light scattering photometer for analysis of single particles has been designed and developed. A fluid stream containing single particles intersects a focused laser beam at the primary focal point of an ellipsoidal reflector ring. The light scattered at angles theta = 2.5 0 to 177.5 0 at phi = 0 0 and 180 0 is reflected onto a circular array of photodiodes. The ellipsoidal reflector is situated in a chamber filled with fluid matching that of the stream to minimize refracting and reflecting interfaces. The detector array consists of 60 photodiodes each subtending 3 0 in scattering angle on 6 0 centers around 360 0 . 32 measurements on individual particles can be acquired at rates of 500 particles per second. The intensity and angular distribution of light scattered by spherical particles are indicative of size and relative refractive index. Calculations, using Lorenz--Mie theory, of differential scattering patterns integrated over angle corresponding to the detector geometry determined the instrument response to particle size. From this the expected resolution and experimental procedures are determined.Ultimately, the photometer will be utilized for identification and discrimination of biological cells based on the sensitivity of light scattering to size, shape, refractive index differences, internal granularity, and other internal morphology. This study has demonstrated the utility of the photometer and indicates potential for application to light scattering studies of biological cells

From single magnetic adatoms on superconductors to coupled spin chains

Science.gov (United States)

Franke, Katharina J.

Magnetic adsorbates on conventional s-wave superconductors lead to exchange interactions that induce Yu-Shiba-Rusinov (YSR) states inside the superconducting energy gap. Here, we employ tunneling spectroscopy at 1.1 K to investigate magnetic atoms and chains on superconducting Pb surfaces. We show that individual Manganese (Mn) atoms give rise to a distinct number of YSR-states. The single-atom junctions are stable over several orders of magnitude in conductance. We identify single-electron tunneling as well as Andreev processes. When the atoms are brought into sufficiently close distance, the Shiba states hybridize, thus giving rise to states with bonding and anti-bonding character. It has been shown that the Pb(110) surface supports the self-assembly of Fe chains, which exhibit fingerprints of Majorana bound states. Using superconducting tips, we resolve a rich subgap structure including peaks at zero energy and low-energy resonances, which overlap with the putative Majorana states. We gratefully acknowledge funding by the Deutsche Forschungsgemeinschaft through collaborative research Grant Sfb 658, and through Grant FR2726/4, as well by the European Research Council through Consolidator Grant NanoSpin.

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.

Analysis of the paired TCR α- and β-chains of single human T cells.

Directory of Open Access Journals (Sweden)

Song-Min Kim

Full Text Available Analysis of the paired i.e. matching TCR α- and β-chain rearrangements of single human T cells is required for a precise investigation of clonal diversity, tissue distribution and specificity of protective and pathologic T-cell mediated immune responses. Here we describe a multiplex RT-PCR based technology, which for the first time allows for an unbiased analysis of the complete sequences of both α- and β-chains of TCR from single T cells. We validated our technology by the analysis of the pathologic T-cell infiltrates from tissue lesions of two T-cell mediated autoimmune diseases, psoriasis vulgaris (PV and multiple sclerosis (MS. In both disorders we could detect various T cell clones as defined by multiple T cells with identical α- and β-chain rearrangements distributed across the tissue lesions. In PV, single cell TCR analysis of lesional T cells identified clonal CD8(+ T cell expansions that predominated in the epidermis of psoriatic plaques. An MS brain lesion contained two dominant CD8(+ T-cell clones that extended over the white and grey matter and meninges. In both diseases several clonally expanded T cells carried dual TCRs composed of one Vβ and two different Vα-chain rearrangements. These results show that our technology is an efficient instrument to analyse αβ-T cell responses with single cell resolution in man. It should facilitate essential new insights into the mechanisms of protective and pathologic immunity in many human T-cell mediated conditions and allow for resurrecting functional TCRs from any αβ-T cell of choice that can be used for investigating their specificity.

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)

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.

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.

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

[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.

Single-frequency blue light generation by single-pass sum-frequency generation in a coupled ring cavity tapered laser

DEFF Research Database (Denmark)

Jensen, Ole Bjarlin; Petersen, Paul Michael

2013-01-01

A generic approach for generation of tunable single frequency light is presented. 340 mW of near diffraction limited, single-frequency, and tunable blue light around 459 nm is generated by sum-frequency generation (SFG) between two tunable tapered diode lasers. One diode laser is operated in a ring...... cavity and another tapered diode laser is single-passed through a nonlinear crystal which is contained in the coupled ring cavity. Using this method, the single-pass conversion efficiency is more than 25%. In contrast to SFG in an external cavity, the system is entirely self-stabilized with no electronic...

White-light-emitting diode based on a single-layer polymer

Science.gov (United States)

Wang, B. Z.; Zhang, X. P.; Liu, H. M.

2013-05-01

A broad-band light-emitting diode was achieved in a single-layer device based on pure poly(9,9'-dioctylfluorene-co-bis-N,N'-(4-butylphenyl)-bis-N,N'-phenyl-1,4-phenylenediamine) (PFB). Electromer emission was observed in the red with a center wavelength of about 620 nm in electroluminescence (EL) spectrum. This kind of emission exhibits strong dependence on the thickness of the PFB layer, so that the shape of the EL spectrum may be adjusted through changing the thickness of the active polymer layer to balance between the intrinsic PFB emission in the blue and the electromer emission in the red. Thus, white light emission may be achieved from such a single-layer single-material diode.

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

Spin canting in a Dy-based single-chain magnet with dominant next-nearest-neighbor antiferromagnetic interactions

Science.gov (United States)

Bernot, K.; Luzon, J.; Caneschi, A.; Gatteschi, D.; Sessoli, R.; Bogani, L.; Vindigni, A.; Rettori, A.; Pini, M. G.

2009-04-01

We investigate theoretically and experimentally the static magnetic properties of single crystals of the molecular-based single-chain magnet of formula [Dy(hfac)3NIT(C6H4OPh)]∞ comprising alternating Dy3+ and organic radicals. The magnetic molar susceptibility χM displays a strong angular variation for sample rotations around two directions perpendicular to the chain axis. A peculiar inversion between maxima and minima in the angular dependence of χM occurs on increasing temperature. Using information regarding the monomeric building block as well as an ab initio estimation of the magnetic anisotropy of the Dy3+ ion, this “anisotropy-inversion” phenomenon can be assigned to weak one-dimensional ferromagnetism along the chain axis. This indicates that antiferromagnetic next-nearest-neighbor interactions between Dy3+ ions dominate, despite the large Dy-Dy separation, over the nearest-neighbor interactions between the radicals and the Dy3+ ions. Measurements of the field dependence of the magnetization, both along and perpendicularly to the chain, and of the angular dependence of χM in a strong magnetic field confirm such an interpretation. Transfer-matrix simulations of the experimental measurements are performed using a classical one-dimensional spin model with antiferromagnetic Heisenberg exchange interaction and noncollinear uniaxial single-ion anisotropies favoring a canted antiferromagnetic spin arrangement, with a net magnetic moment along the chain axis. The fine agreement obtained with experimental data provides estimates of the Hamiltonian parameters, essential for further study of the dynamics of rare-earth-based molecular chains.

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.

Alternative types of molecule-decorated atomic chains in Au–CO–Au single-molecule junctions

Directory of Open Access Journals (Sweden)

Zoltán Balogh

2015-06-01

Full Text Available We investigate the formation and evolution of Au–CO single-molecule break junctions. The conductance histogram exhibits two distinct molecular configurations, which are further investigated by a combined statistical analysis. According to conditional histogram and correlation analysis these molecular configurations show strong anticorrelations with each other and with pure Au monoatomic junctions and atomic chains. We identify molecular precursor configurations with somewhat higher conductance, which are formed prior to single-molecule junctions. According to detailed length analysis two distinct types of molecule-affected chain-formation processes are observed, and we compare these results to former theoretical calculations considering bridge- and atop-type molecular configurations where the latter has reduced conductance due to destructive Fano interference.

Jet and ultrasonic nebulization of single chain urokinase plasminogen activator (scu-PA)

DEFF Research Database (Denmark)

Münster, Anna-Marie; Bendstrup, E; Jensen, J.I.

2000-01-01

locally by nebulization in a recombinant zymogen form as single chain urokinase plasminogen activator (scu-PA). We aimed to characterize the particle size distribution, drug output, and enzymatic activity of scu-PA after nebulization with a Ventstream jet nebulizer (Medic-Aid, Bognor Regis, UK) and a Syst...

Finite-size effects on the static properties of a single-chain magnet

Science.gov (United States)

Bogani, L.; Sessoli, R.; Pini, M. G.; Rettori, A.; Novak, M. A.; Rosa, P.; Massi, M.; Fedi, M. E.; Giuntini, L.; Caneschi, A.; Gatteschi, D.

2005-08-01

We study the role of defects in the “single-chain magnet” CoPhOMe by inserting a controlled number of diamagnetic impurities. The samples are analyzed with unprecedented accuracy with the particle induced x-ray emission technique, and with ac and dc magnetic measurements. In an external applied field the system shows an unexpected behavior, giving rise to a double peak in the susceptibility. The static thermodynamic properties of the randomly diluted Ising chain with alternating g values are then exactly obtained via a transfer matrix approach. These results are compared to the experimental behavior of CoPhOMe, showing qualitative agreement.

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.

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.

Efficient and bright organic light-emitting diodes on single-layer graphene electrodes

Science.gov (United States)

Li, Ning; Oida, Satoshi; Tulevski, George S.; Han, Shu-Jen; Hannon, James B.; Sadana, Devendra K.; Chen, Tze-Chiang

2013-08-01

Organic light-emitting diodes are emerging as leading technologies for both high quality display and lighting. However, the transparent conductive electrode used in the current organic light-emitting diode technologies increases the overall cost and has limited bendability for future flexible applications. Here we use single-layer graphene as an alternative flexible transparent conductor, yielding white organic light-emitting diodes with brightness and efficiency sufficient for general lighting. The performance improvement is attributed to the device structure, which allows direct hole injection from the single-layer graphene anode into the light-emitting layers, reducing carrier trapping induced efficiency roll-off. By employing a light out-coupling structure, phosphorescent green organic light-emitting diodes exhibit external quantum efficiency >60%, while phosphorescent white organic light-emitting diodes exhibit external quantum efficiency >45% at 10,000 cd m-2 with colour rendering index of 85. The power efficiency of white organic light-emitting diodes reaches 80 lm W-1 at 3,000 cd m-2, comparable to the most efficient lighting technologies.

From single Debye-Hückel chains to polyelectrolyte solutions: Simulation results

Science.gov (United States)

Kremer, Kurt

1996-03-01

This lecture will present results from simulations of single weakly charged flexible chains, where the electrostatic part of the interaction is modeled by a Debye-Hückel potential,( with U. Micka, IFF, Forschungszentrum Jülich, 52425 Jülich, Germany) as well as simulations of polyelectrolyte solutions, where the counterions are explicitly taken into account( with M. J. Stevens, Sandia Nat. Lab., Albuquerque, NM 87185-1111) ( M. J. Stevens, K. Kremer, JCP 103), 1669 (1995). The first set of the simulations is meant to clear a recent contoversy on the dependency of the persistence length LP on the screening length Γ. While the analytic theories give Lp ~ Γ^x with either x=1 or x=2, the simulations find for all experimentally accessible chain lengths a varying exponent, which is significantly smaller than 1. This causes serious doubts on the applicability of this model for weakly charged polyelectrolytes in general. The second part deals with strongly charged flexible polyelectrolytes in salt free solution. These simulations are performed for multichain systems. The full Coulomb interactions of the monomers and counterions are treated explicitly. Experimental measurements of the osmotic pressure and the structure factor are reproduced and extended. The simulations reveal a new picture of the chain structure based on calculations of the structure factor, persistence length, end-to-end distance, etc. Even at very low density, the chains show significant bending. Furthermore, the chains contract significantly before they start to overlap. We also show that counterion condensation dramatically alters the chain structure, even for a good solvent backbone.

Properties, production and applications of camelid single-domain antibody fragments

NARCIS (Netherlands)

Harmsen, M.M.; Haard, de H.J.

2007-01-01

Camelids produce functional antibodies devoid of light chains of which the single N-terminal domain is fully capable of antigen binding. These single-domain antibody fragments (VHHs or Nanobodies®) have several advantages for biotechnological applications. They are well expressed in microorganisms

Premenstrual mood and empathy after a single light therapy session

NARCIS (Netherlands)

aan het Rot, Marije; Miloserdov, Kristina; Buijze, Anna L. F.; Meesters, Ybe; Gordijn, Marijke C. M.

2017-01-01

To examine whether acute changes in cognitive empathy might mediate the impact of light therapy on mood, we assessed the effects of a single light-therapy session on mood and cognitive empathy in 48 premenstrual women, including 17 who met Premenstrual Symptoms Screening Tool criteria for

3D single-molecule super-resolution microscopy with a tilted light sheet.

Science.gov (United States)

Gustavsson, Anna-Karin; Petrov, Petar N; Lee, Maurice Y; Shechtman, Yoav; Moerner, W E

2018-01-09

Tilted light sheet microscopy with 3D point spread functions (TILT3D) combines a novel, tilted light sheet illumination strategy with long axial range point spread functions (PSFs) for low-background, 3D super-localization of single molecules as well as 3D super-resolution imaging in thick cells. Because the axial positions of the single emitters are encoded in the shape of each single-molecule image rather than in the position or thickness of the light sheet, the light sheet need not be extremely thin. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The result is simple and flexible 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validate TILT3D for 3D super-resolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed tetrapod PSFs for fiducial bead tracking and live axial drift correction.

Interaction of a single mode field cavity with the 1D XY model: Energy spectrum

International Nuclear Information System (INIS)

Tonchev, H; Donkov, A A; Chamati, H

2016-01-01

In this work we use the fundamental in quantum optics Jaynes-Cummings model to study the response of spin 1/2chain to a single mode of a laser light falling on one of the spins, a focused interaction model between the light and the spin chain. For the spin-spin interaction along the chain we use the XY model. We report here the exact analytical results, obtained with the help of a computer algebra system, for the energy spectrum in this model for chains of up to 4 spins with nearest neighbors interactions, either for open or cyclic chain configurations. Varying the sign and magnitude of the spin exchange coupling relative to the light-spin interaction we have investigated both cases of ferromagnetic or antiferromagnetic spin chains. (paper)

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.

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

Conductance of single microRNAs chains related to the autism spectrum disorder

Science.gov (United States)

Oliveira, J. I. N.; Albuquerque, E. L.; Fulco, U. L.; Mauriz, P. W.; Sarmento, R. G.; Caetano, E. W. S.; Freire, V. N.

2014-09-01

The charge transport properties of single-stranded microRNAs (miRNAs) chains associated to autism disorder were investigated. The computations were performed within a tight-binding model, together with a transfer matrix technique, with ionization energies and hopping parameters obtained by quantum chemistry method. Current-voltage (I× V) curves of twelve miRNA chains related to the autism spectrum disorders were calculated and analysed. We have obtained both semiconductor and insulator behavior, and a relationship between the current intensity and the autism-related miRNA bases sequencies, suggesting that a kind of electronic biosensor can be developed to distinguish different profiles of autism disorders.

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...

Creation of Single Chain of Nanoscale Skyrmion Bubbles with Record-high Temperature Stability in a Geometrically Confined Nanostripe

KAUST Repository

Hou, Zhipeng; Zhang, Qiang; Xu, Guizhou; Gong, Chen; Ding, Bei; Wang, Yue; Li, Hang; Liu, Enke; Xu, Feng; Zhang, Hongwei; Yao, Yuan; Wu, Guangheng; Zhang, Xixiang; Wang, Wenhong

2018-01-01

Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.

Creation of Single Chain of Nanoscale Skyrmion Bubbles with Record-high Temperature Stability in a Geometrically Confined Nanostripe

KAUST Repository

Hou, Zhipeng

2018-01-04

Nanoscale topologically nontrivial spin textures, such as magnetic skyrmions, have been identified as promising candidates for the transport and storage of information for spintronic applications, notably magnetic racetrack memory devices. The design and realization of a single skyrmion chain at room temperature (RT) and above in the low-dimensional nanostructures are of great importance for future practical applications. Here, we report the creation of a single skyrmion bubble chain in a geometrically confined Fe3Sn2 nanostripe with a width comparable to the featured size of a skyrmion bubble. Systematic investigations on the thermal stability have revealed that the single chain of skyrmion bubbles can keep stable at temperatures varying from RT up to a record-high temperature of 630 K. This extreme stability can be ascribed to the weak temperature-dependent magnetic anisotropy and the formation of edge states at the boundaries of the nanostripes. The realization of the highly stable skyrmion bubble chain in a geometrically confined nanostructure is a very important step toward the application of skyrmion-based spintronic devices.

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.

Single-strand breaks induced in Bacillus subtilis DNA by ultraviolet light: action spectrum and properties

International Nuclear Information System (INIS)

Peak, M.J.; Peak, J.G.

1982-01-01

The induction of single-strand breaks (alkali-labile bonds plus frank breaks) in the DNA of Bacillus subtilis irradiated in vivo by monochromatic UV light at wavelengths from 254 to 434nm was measured. The spectrum consists of a major far-UV (below 320nm) component and a minor near-UV shoulder. A mutant deficient in DNA polymerase I accumulates breaks caused by near-UV (above 320nm) wavelengths faster than the wild-type strain proficient in polymerase I. Measurable breaks in extracted DNA are induced at a higher frequency than those induced in vivo. Anoxia, glycerol, and diazobicyclo (2.2.2.) octane inhibit break formation in extracted DNA. Alkali-labile bonds induced by 365-nm UV radiation are largely (78%) covalent bond chain breaks, the remainder consists of true alkali-labile bonds, probably apurinic and apyrimidinic sites. (author)

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.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten; Luka-Guth, Katharina; Wieser, Matthias; Lokamani; Wolf, Jannic Sebastian; Helm, Manfred; Gemming, Sibylle; Kerbusch, Jochen; Scheer, Elke; Huhn, Thomas; Erbe, Artur

2015-01-01

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Light-Induced Switching of Tunable Single-Molecule Junctions

KAUST Repository

Sendler, Torsten

2015-04-16

A major goal of molecular electronics is the development and implementation of devices such as single-molecular switches. Here, measurements are presented that show the controlled in situ switching of diarylethene molecules from their nonconductive to conductive state in contact to gold nanoelectrodes via controlled light irradiation. Both the conductance and the quantum yield for switching of these molecules are within a range making the molecules suitable for actual devices. The conductance of the molecular junctions in the opened and closed states is characterized and the molecular level E 0, which dominates the current transport in the closed state, and its level broadening Γ are identified. The obtained results show a clear light-induced ring forming isomerization of the single-molecule junctions. Electron withdrawing side-groups lead to a reduction of conductance, but do not influence the efficiency of the switching mechanism. Quantum chemical calculations of the light-induced switching processes correlate these observations with the fundamentally different low-lying electronic states of the opened and closed forms and their comparably small modification by electron-withdrawing substituents. This full characterization of a molecular switch operated in a molecular junction is an important step toward the development of real molecular electronics devices.

Single-chain vascular endothelial growth factor variant with antagonist activity

DEFF Research Database (Denmark)

Boesen, Thomas P; Soni, Bobby; Schwartz, Thue W

2002-01-01

receptor molecules and inducing dimerization. By mixing two vascular endothelial growth factor monomers, each with different substitutions, heterodimers with only one active receptor binding site have previously been prepared. These heterodimers bind the receptor molecule but are unable to induce...... dimerization and activation. However, preparation of heterodimers is cumbersome, involving separate expression of different monomers, refolding the mixture, and separating heterodimers from homodimers. Here we show that a fully functional ligand can efficiently be expressed as a single protein chain containing...

The in vivo characteristics of genetically engineered divalent and tetravalent single-chain antibody constructs

International Nuclear Information System (INIS)

Wittel, Uwe A.; Jain, Maneesh; Goel, Apollina; Chauhan, Subhash C.; Colcher, David; Batra, Surinder K.

2005-01-01

Engineered multivalent single-chain Fv (scFv) constructs have been demonstrated to exhibit rapid blood clearance and better tumor penetration. To understand the short plasma half-life of multivalent single-chain antibody fragments, the pharmacokinetic properties of covalent dimeric scFv [sc(Fv) 2 ], noncovalent tetrameric scFv {[sc(Fv) 2 ] 2 } and IgG of MAb CC49 were examined. The scFvs displayed an ability to form higher molecular aggregates in vivo. A specific proteolytic cleavage of the linker sequence of the covalent dimeric or a deterioration of the noncovalent association of the dimeric scFv into tetravalent scFv constructs was not observed. In conclusion, sc(Fv) 2 and [sc(Fv) 2 ] 2 are stable in vivo and have significant potential for diagnostic and therapeutic applications

Surface water retardation around single-chain polymeric nanoparticles: critical for catalytic function?

Science.gov (United States)

Stals, Patrick J M; Cheng, Chi-Yuan; van Beek, Lotte; Wauters, Annelies C; Palmans, Anja R A; Han, Songi; Meijer, E W

2016-03-01

A library of water-soluble dynamic single-chain polymeric nanoparticles (SCPN) was prepared using a controlled radical polymerisation technique followed by the introduction of functional groups, including probes at targeted positions. The combined tools of electron paramagnetic resonance (EPR) and Overhauser dynamic nuclear polarization (ODNP) reveal that these SCPNs have structural and surface hydration properties resembling that of enzymes.

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...

Experimental studies of the dynamic mechanical response of a single polymer chain

DEFF Research Database (Denmark)

Thormann, Esben; Evans, Drew R.; Craig, Vincent S. J.

2006-01-01

The high-frequency and low-amplitude dynamic mechanical response from a single poly(vinyl alcohol) chain was investigated. Modification of a commercial atomic force microscope enabled high-frequency and low-amplitude periodic deformations of polymer chains during extension to be performed...... mechanical response from poly(vinyl alcohol) does not differ from its static response. This result is not unexpected as poly(vinyl alcohol) is a highly flexible polymer with intramolecular relaxation processes taking place on a short time scale. The choice of a polymer with a fast relaxation allows its...... static properties to be recovered from the dynamic measurements and enables the method suggested in this paper for decoupling the polymer response from the hydrodynamic response to be validated....

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.

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.

High luminous flux from single crystal phosphor-converted laser-based white lighting system

KAUST Repository

Cantore, Michael

2015-12-14

The efficiency droop of light emitting diodes (LEDs) with increasing current density limits the amount of light emitted per wafer area. Since low current densities are required for high efficiency operation, many LED die are needed for high power white light illumination systems. In contrast, the carrier density of laser diodes (LDs) clamps at threshold, so the efficiency of LDs does not droop above threshold and high efficiencies can be achieved at very high current densities. The use of a high power blue GaN-based LD coupled with a single crystal Ce-doped yttrium aluminum garnet (YAG:Ce) sample was investigated for white light illumination applications. Under CW operation, a single phosphor-converted LD (pc-LD) die produced a peak luminous efficacy of 86.7 lm/W at 1.4 A and 4.24 V and a peak luminous flux of 1100 lm at 3.0 A and 4.85 V with a luminous efficacy of 75.6 lm/W. Simulations of a pc-LD confirm that the single crystal YAG:Ce sample did not experience thermal quenching at peak LD operating efficiency. These results show that a single pc-LD die is capable of emitting enough luminous flux for use in a high power white light illumination system.

Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes

Science.gov (United States)

Raithel, Dominic; Simine, Lena; Pickel, Sebastian; Schötz, Konstantin; Panzer, Fabian; Baderschneider, Sebastian; Schiefer, Daniel; Lohwasser, Ruth; Köhler, Jürgen; Thelakkat, Mukundan; Sommer, Michael; Köhler, Anna; Rossky, Peter J.; Hildner, Richard

2018-03-01

The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (˜2,000 cm‑1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron‑hole polarization.

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.

A detailed comparison of single-camera light-field PIV and tomographic PIV

Science.gov (United States)

Shi, Shengxian; Ding, Junfei; Atkinson, Callum; Soria, Julio; New, T. H.

2018-03-01

This paper conducts a comprehensive study between the single-camera light-field particle image velocimetry (LF-PIV) and the multi-camera tomographic particle image velocimetry (Tomo-PIV). Simulation studies were first performed using synthetic light-field and tomographic particle images, which extensively examine the difference between these two techniques by varying key parameters such as pixel to microlens ratio (PMR), light-field camera Tomo-camera pixel ratio (LTPR), particle seeding density and tomographic camera number. Simulation results indicate that the single LF-PIV can achieve accuracy consistent with that of multi-camera Tomo-PIV, but requires the use of overall greater number of pixels. Experimental studies were then conducted by simultaneously measuring low-speed jet flow with single-camera LF-PIV and four-camera Tomo-PIV systems. Experiments confirm that given a sufficiently high pixel resolution, a single-camera LF-PIV system can indeed deliver volumetric velocity field measurements for an equivalent field of view with a spatial resolution commensurate with those of multi-camera Tomo-PIV system, enabling accurate 3D measurements in applications where optical access is limited.

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.

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.

Single step, pH induced gold nanoparticle chain formation in lecithin/water system.

Science.gov (United States)

Sharma, Damyanti

2013-07-01

Gold nanoparticle (AuNP) chains have been formed by a single step method in a lecithin/water system where lecithin itself plays the role of a reductant and a template for AuNP chain formation. Two preparative strategies were explored: (1) evaporating lecithin solution with aqueous gold chloride (HAuCl4) at different pHs and (2) dispersing lecithin vesicles in aqueous HAuCl4 solutions of various pHs in the range of 2.5-11.3. In method 1, at initial pH 2.5, 20-50 nm AuNPs are found attached to lecithin vesicles. When pH is raised to 5.5 there are no vesicles present and 20 nm monodisperse particles are found aggregating. Chain formation of fine nanoparticles (3-5 nm) is observed from neutral to basic pH, between 6.5-10.3 The chains formed are hundreds of nanometers to micrometer long and are usually 2-3 nanoparticles wide. On further increasing pH to 11.3, particles form disk-like or raft-like structures. When method (ii) was used a little chain formation was observed. Most of the nanoparticles formed were found either sitting together as raft like structures or scattered on lecithin structures. Copyright © 2013 Elsevier B.V. All rights reserved.

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.

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.
.

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

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.

Kinetic analysis of a monoclonal therapeutic antibody and its single-chain homolog by surface plasmon resonance.

Science.gov (United States)

Patel, Rekha; Andrien, Bruce A

2010-01-01

Monoclonal antibodies (mAbs) and antibody fragments have become an emerging class of therapeutics since 1986. Their versatility enables them to be engineered for optimal efficiency and decreased immunogenicity, and the path to market has been set by recent regulatory approvals. One of the initial criteria for success of any protein or antibody therapeutic is to understand its binding characteristics to the target antigen. Surface plasmon resonance (SPR) has been widely used and is an important tool for ligand-antigen binding characterization. In this work, the binding kinetics of a recombinant mAb and its single-chain antibody homolog, single-chain variable fragment (scFv), was analyzed by SPR. These two proteins target the same antigen. The binding kinetics of the mAb (bivalent antibody) and scFv (monovalent scFv) for this antigen was analyzed along with an assessment of the thermodynamics of the binding interactions. Alternative binding configurations were investigated to evaluate potential experimental bias because theoretically experimental binding configuration should have no impact on binding kinetics. Self-association binding kinetics in the proteins' respective formulation solutions and antigen epitope mapping were also evaluated. Functional characterization of monoclonal and single-chain antibodies has become just as important as structural characterization in the biotechnology field.

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...

Efficient sampling of reversible cross-linking polymers: Self-assembly of single-chain polymeric nanoparticles

Science.gov (United States)

Oyarzún, Bernardo; Mognetti, Bortolo Matteo

2018-03-01

We present a new simulation technique to study systems of polymers functionalized by reactive sites that bind/unbind forming reversible linkages. Functionalized polymers feature self-assembly and responsive properties that are unmatched by the systems lacking selective interactions. The scales at which the functional properties of these materials emerge are difficult to model, especially in the reversible regime where such properties result from many binding/unbinding events. This difficulty is related to large entropic barriers associated with the formation of intra-molecular loops. In this work, we present a simulation scheme that sidesteps configurational costs by dedicated Monte Carlo moves capable of binding/unbinding reactive sites in a single step. Cross-linking reactions are implemented by trial moves that reconstruct chain sections attempting, at the same time, a dimerization reaction between pairs of reactive sites. The model is parametrized by the reaction equilibrium constant of the reactive species free in solution. This quantity can be obtained by means of experiments or atomistic/quantum simulations. We use the proposed methodology to study the self-assembly of single-chain polymeric nanoparticles, starting from flexible precursors carrying regularly or randomly distributed reactive sites. We focus on understanding differences in the morphology of chain nanoparticles when linkages are reversible as compared to the well-studied case of irreversible reactions. Intriguingly, we find that the size of regularly functionalized chains, in good solvent conditions, is non-monotonous as a function of the degree of functionalization. We clarify how this result follows from excluded volume interactions and is peculiar of reversible linkages and regular functionalizations.

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...

Single-fiber myosin heavy chain polymorphism during postnatal development: modulation by hypothyroidism

Science.gov (United States)

di Maso, N. A.; Caiozzo, V. J.; Baldwin, K. M.

2000-01-01

The primary objective of this study was to follow the developmental time course of myosin heavy chain (MHC) isoform transitions in single fibers of the rodent plantaris muscle. Hypothyroidism was used in conjunction with single-fiber analyses to better describe a possible linkage between the neonatal and fast type IIB MHC isoforms during development. In contrast to the general concept that developmental MHC isoform transitions give rise to muscle fibers that express only a single MHC isoform, the single-fiber analyses revealed a very high degree of MHC polymorphism throughout postnatal development. In the adult state, MHC polymorphism was so pervasive that the rodent plantaris muscles contained approximately 12-15 different pools of fibers (i.e., fiber types). The degree of polymorphism observed at the single-fiber level made it difficult to determine specific developmental schemes analogous to those observed previously for the rodent soleus muscle. However, hypothyroidism was useful in that it confirmed a possible link between the developmental regulation of the neonatal and fast type IIB MHC isoforms.

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.

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.

Construction and Self-Assembly of Single-Chain Polymer Nanoparticles via Coordination Association and Electrostatic Repulsion in Water.

Science.gov (United States)

Zhu, Zhengguang; Xu, Na; Yu, Qiuping; Guo, Lei; Cao, Hui; Lu, Xinhua; Cai, Yuanli

2015-08-01

Simultaneous coordination-association and electrostatic-repulsion interactions play critical roles in the construction and stabilization of enzymatic function metal centers in water media. These interactions are promising for construction and self-assembly of artificial aqueous polymer single-chain nanoparticles (SCNPs). Herein, the construction and self-assembly of dative-bonded aqueous SCNPs are reported via simultaneous coordination-association and electrostatic-repulsion interactions within single chains of histamine-based hydrophilic block copolymer. The electrostatic-repulsion interactions are tunable through adjusting the imidazolium/imidazole ratio in response to pH, and in situ Cu(II)-coordination leads to the intramolecular association and single-chain collapse in acidic water. SCNPs are stabilized by the electrostatic repulsion of dative-bonded block and steric shielding of nonionic water-soluble block, and have a huge specific surface area of function metal centers accessible to substrates in acidic water. Moreover, SCNPs can assemble into micelles, networks, and large particles programmably in response to the solution pH. These unique media-sensitive phase-transformation behaviors provide a general, facile, and versatile platform for the fabrication of enzyme-inspired smart aqueous catalysts. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Mediating Dynamic Supply Chain Formation by Collaborative Single Machine Earliness/Tardiness Agents in Supply Mesh

Directory of Open Access Journals (Sweden)

Hang Yang

2014-01-01

Full Text Available Nowadays, a trend of forming dynamic supply chains with different trading partners over different e-marketplaces has emerged. These supply chains, which are called “supply mesh,” generally refer to heterogeneous electronic marketplaces in which dynamic supply chains, as per project (often make-to-order, are formed across different parties. Conceptually, in a supply mesh a dynamic supply chain is formed vertically, mediating several companies for a project. Companies that are on the same level horizontally are either competitors or cohorts. A complex scenario such as this makes it challenging to find the right group of members for a dynamic supply chain. Earlier on, a multiagent model called the collaborative single machine earliness/tardiness (CSET model was proposed for the optimal formation of make-to-order supply chains. This paper contributes the particular agent designs, for enabling the mediation of CSET in a supply mesh, and the possibilities are discussed. It is demonstrated via a computer simulation, based on samples from the U.S. textile industry, that by using intelligent agents under the CSET model it is possible to automatically find an ideal group of trading partners from a supply mesh.

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.

First-order reversal curves of single domain particles: diluted random assemblages and chains

Science.gov (United States)

Egli, R.

2009-04-01

Exact magnetic models can be used to calculate first-order reversal curves (FORC) of single domain (SD) particle assemblages, as shown by Newell [2005] for the case of isolated Stoner-Wohlfarth particles. After overcoming experimental difficulties, a FORC diagram sharing many similarities to Newell's model has been measured on a lake sediment sample (see A.P. Chen et al., "Quantification of magnetofossils using first-order reversal curves", EGU General Assembly 2009, Abstracts Vol. 11, EGU2009-10719). This sample contains abundant magnetofossils, as shown by coercivity analysis and electron microscopy, therefore suggesting that well dispersed, intact magnetosome chains are the main SD carriers. Subtle differences between the reversible and the irreversible contributions of the measured FORC distribution suggest that magnetosome chains might not be correctly described by the Stoner-Wohlfarth model. To better understand the hysteresis properties of such chains, a simple magnetic model has been implemented, taking dipole-dipole interactions between particles within the same chain into account. The model results depend on the magnetosome elongation, the number of magnetosomes in a chain, and the gap between them. If the chain axis is subparallel to the applied field, the magnetic moment reverses by a pseudo-fanning mode, which is replaced by a pseudo-coherent rotation mode at greater angles. These reversal modes are intrinsically different from coherent rotation assumed Stoner-Wohlfarth model, resulting in FORC diagrams with a smaller reversible component. On the other hand, isolated authigenic SD particles can precipitate in the sediment matrix, as it might occur for pedogenic magnetite. In this case, an assembly of randomly located particles provides a possible model for the resulting FORC diagram. If the concentration of the particles is small, each particle is affected by a random interaction field whose statistical distribution can be calculated from first

Quantum phase transitions driven by rhombic-type single-ion anisotropy in the S =1 Haldane chain

Science.gov (United States)

Tzeng, Yu-Chin; Onishi, Hiroaki; Okubo, Tsuyoshi; Kao, Ying-Jer

2017-08-01

The spin-1 Haldane chain is an example of the symmetry-protected-topological (SPT) phase in one dimension. Experimental realization of the spin chain materials usually involves both the uniaxial-type, D (Sz)2 , and the rhombic-type, E [(Sx)2-(Sy)2] , single-ion anisotropies. Here, we provide a precise ground-state phase diagram for a spin-1 Haldane chain with these single-ion anisotropies. Using quantum numbers, we find that the Z2 symmetry breaking phase can be characterized by double degeneracy in the entanglement spectrum. Topological quantum phase transitions take place on particular paths in the phase diagram, from the Haldane phase to the large-Ex, large-Ey, or large-D phases. The topological critical points are determined by the level spectroscopy method with a newly developed parity technique in the density matrix renormalization group [Phys. Rev. B 86, 024403 (2012), 10.1103/PhysRevB.86.024403], and the Haldane-large-D critical point is obtained with an unprecedented precision, (D/J ) c=0.9684713 (1 ) . Close to this critical point, a small rhombic single-ion anisotropy |E |/J ≪1 can destroy the Haldane phase and bring the system into a y -Néel phase. We propose that the compound [Ni (HF2) (3-Clpy ) 4] BF4 is a candidate system to search for the y -Néel phase.

Magnetic properties of CsCrCl/sub 3/, an antiferromagnetic chain compound with single-ion anisotropy

Energy Technology Data Exchange (ETDEWEB)

Day, P; Gregson, A K; Leech, D H [Oxford Univ. (UK). Inorganic Chemistry Lab.; Hutchings, M T [UKAEA Atomic Energy Research Establishment, Harwell. Materials Physics Div.; Rainford, B D [Imperial Coll. of Science and Technology, London (UK). Dept. of Physics

1979-01-01

The magnetic structure and excitations of the linear chain hexagonal perovskite salt CsCrCl/sub 3/ have been studied by susceptibility, powder and single crystal neutron diffraction, and coherent inelastic neutron scattering. Below the Neel temperature, Tsub(N) = 16 K, the spins lie in the basal plane with antiferromagnetic ordering along the c-axis chains. At 4.5 K there is strong dispersion of the spin-wave energy along c but no measurable dispersion perpendicular to c.

Single photon light detector for deep ocean applications

International Nuclear Information System (INIS)

Matsuno, S.; Babson, J.; Learned, J.G.; O'Connor, D.; Grieder, P.K.F.; Wilson, C.

1989-01-01

We have developed a single photon sensitive light detector module which can be operated in the ocean to a depth of 5000 m. It was designed primarily to be used as a Cherenkov light detector in conjunction with the DUMAND (Deep Underwater Muon And Neutrino Detector) experiment. After calibration in the laboratory, seven detectors, assembled in a vertical string geometry, have been operated simultaneously in the deep ocean off the coast of the island of Hawaii. Cosmic ray muons have been recorded successfully at dephts ranging from 2000 to 4000 m. The results have demonstrated the capability of the detector; it fulfills the specifications required for the modules to be used in a deep ocean muon and neutrino detector. (orig.)

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.

Integrated single- and two-photon light sheet microscopy using accelerating beams

DEFF Research Database (Denmark)

Piksarv, Peeter; Marti, Dominik; Le, Tuan

2017-01-01

We demonstrate the first light sheet microscope using propagation invariant, accelerating Airy beams that operates both in single- and two-photon modes. The use of the Airy beam permits us to develop an ultra compact, high resolution light sheet system without beam scanning. In two-photon mode......, an increase in the field of view over the use of a standard Gaussian beam by a factor of six is demonstrated. This implementation for light sheet microscopy opens up new possibilities across a wide range of biomedical applications, especially for the study of neuronal processes....

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.

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.

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.

Membrane potential and microsecond to millisecond delayed light emission after a single excitation flash in isolated chloroplasts

International Nuclear Information System (INIS)

Jursinic, P.; Govindjee; Wraight, C.A.

1978-01-01

The effect of light-induced and salt-jump induced membrane potential on microsecond and millisecond delayed light emission from chloroplasts, following a single 10 ns flash, have been studied. Microsecond delayed light emission is shown to be independent of the membrane potential contrary to proposals that the activation energy for delayed light emission can be modulated by transmembrane electric fields. This result is discussed in terms of the possible origin of this short-lived emission. Millisecond delayed light after a single excitation flash is enhanced by membrane potential only if a proton gradient is present. By measuring changes in ms delayed light caused by simultaneous injection of KCl and Na-benzoate (which creates a proton gradient) in the presence of valinomycin, the light-induced potential generated across the thylakoid membrane by a single excitation flash was calibrated and found to be 128 +- 10 mV in agreement with the recent measurements of Zickler and Witt, (FEBS Lett. 66, 142-148 (1976)), based on voltage-dependent ionophores. It is concluded that the secondary charges that give rise to ms delayed light, after a single flash, do not fully span the membrane. (author)

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.

Monte Carlo simulated dynamical magnetization of single-chain magnets

Energy Technology Data Exchange (ETDEWEB)

Li, Jun; Liu, Bang-Gui, E-mail: bgliu@iphy.ac.cn

2015-03-15

Here, a dynamical Monte-Carlo (DMC) method is used to study temperature-dependent dynamical magnetization of famous Mn{sub 2}Ni system as typical example of single-chain magnets with strong magnetic anisotropy. Simulated magnetization curves are in good agreement with experimental results under typical temperatures and sweeping rates, and simulated coercive fields as functions of temperature are also consistent with experimental curves. Further analysis indicates that the magnetization reversal is determined by both thermal-activated effects and quantum spin tunnelings. These can help explore basic properties and applications of such important magnetic systems. - Highlights: • Monte Carlo simulated magnetization curves are in good agreement with experimental results. • Simulated coercive fields as functions of temperature are consistent with experimental results. • The magnetization reversal is understood in terms of the Monte Carlo simulations.

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.

The exact solution of the Ising quantum chain with alternating single and sector defects

International Nuclear Information System (INIS)

Zhang Degang; Li Bozang; Li Yun

1992-10-01

The Ising quantum chain with alternating single and sector defects is solved exactly by using the technique of Lieb, Schultz and Mattis. The energy spectrum of this model is shown to have a tower structure if and only if these defects constitute a commensurate configuration. This means that conformal invariance is preserved under these circumstances. (author). 13 refs

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.

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.

A uranium-based UO_2"+-Mn"2"+ single-chain magnet assembled trough cation-cation interactions

International Nuclear Information System (INIS)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella; Caciuffo, Roberto; Colineau, Eric; Tuna, Floriana; Magnani, Nicola; Geyer, Arnaud de

2014-01-01

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]_n, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO_2(salen)py][Cp"*_2Co] (Cp"*=pentamethylcyclopentadienyl) with Cd(NO_3)_2 or Mn(NO_3)_2 in pyridine. The infinite UMn chain displays a high relaxation barrier of 134±0.8 K (93±0.5 cm"-"1), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T<6 K, with an impressive coercive field of 3.4 T at 2 K.

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

Characterization of a Single Chain Fv Antibody that Reacts with Free Morphine

OpenAIRE

Matsukizono, Miho; Kamegawa, Mariko; Tanaka, Koichi; Kohra, Shinya; Arizono, Koji; Hamazoe, Yuta; Sugimura, Kazuhisa

2013-01-01

An immune phage library derived from mice, hyperimmunized with morphine-conjugated BSA, was used to isolate a single-chain Fv (scFv) clone, M86, with binding activity to morphine-conjugated thyroglobulin (morphine-C-Tg) but not to codeine-, cocaine-, or ketamine-conjugated Tg. Surface plasmon resonance analysis using a morphine-C-Tg-coupled CM5 sensor chip showed that the Kd value was 1.26 × 10−8 M. To analyze its binding activity to free morphine and related compounds, we performed a competi...

The generation and selection of single-domain, v region libraries from nurse sharks.

Science.gov (United States)

Flajnik, Martin F; Dooley, Helen

2009-01-01

The cartilaginous fish (sharks, skates, and rays) are the oldest phylogenetic group in which a human-type adaptive immune system and immunoglobulins (Igs) have been found. In addition to their conventional (heavy-light chain heterodimeric) isotypes, IgM and IgW, sharks produce the novel isotype, IgNAR, a heavy chain homodimer that does not associate with light chains. Instead, its variable (V) regions act as independent, soluble units in order to bind antigen. In this chapter, we detail our immunization protocol in order to raise a humoral IgNAR response in the nurse shark (Ginglymostoma cirratum) and the subsequent cloning of the single-domain V regions from this isotype in order to select antigen-specific binders by phage display.

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.

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.

Growth and development of Arabidopsis thaliana under single-wavelength red and blue laser light

KAUST Repository

Ooi, Amanda Siok Lee

2016-09-23

Indoor horticulture offers a sensible solution for sustainable food production and is becoming increasingly widespread. However, it incurs high energy and cost due to the use of artificial lighting such as high-pressure sodium lamps, fluorescent light or increasingly, the light-emitting diodes (LEDs). The energy efficiency and light quality of currently available horticultural lighting is suboptimal, and therefore less than ideal for sustainable and cost-effective large-scale plant production. Here, we demonstrate the use of high-powered single-wavelength lasers for indoor horticulture. They are highly energy-efficient and can be remotely guided to the site of plant growth, thus reducing on-site heat accumulation. Furthermore, laser beams can be tailored to match the absorption profiles of different plant species. We have developed a prototype laser growth chamber and demonstrate that plants grown under laser illumination can complete a full growth cycle from seed to seed with phenotypes resembling those of plants grown under LEDs reported previously. Importantly, the plants have lower expression of proteins diagnostic for light and radiation stress. The phenotypical, biochemical and proteome data show that the single-wavelength laser light is suitable for plant growth and therefore, potentially able to unlock the advantages of this next generation lighting technology for highly energy-efficient horticulture.

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.

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

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.

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.

Single nanowire green InGaN/GaN light emitting diodes

Science.gov (United States)

Zhang, Guogang; Li, Ziyuan; Yuan, Xiaoming; Wang, Fan; Fu, Lan; Zhuang, Zhe; Ren, Fang-Fang; Liu, Bin; Zhang, Rong; Tan, Hark Hoe; Jagadish, Chennupati

2016-10-01

Single nanowire (NW) green InGaN/GaN light-emitting diodes (LEDs) were fabricated by top-down etching technology. The electroluminescence (EL) peak wavelength remains approximately constant with an increasing injection current in contrast to a standard planar LED, which suggests that the quantum-confined Stark effect is significantly reduced in the single NW device. The strain relaxation mechanism is studied in the single NW LED using Raman scattering analysis. As compared to its planar counterpart, the EL peak of the NW LED shows a redshift, due to electric field redistribution as a result of changes in the cavity mode pattern after metallization. Our method has important implication for single NW optoelectronic device applications.

UVSiPM: A light detector instrument based on a SiPM sensor working in single photon counting

Energy Technology Data Exchange (ETDEWEB)

Sottile, G.; Russo, F.; Agnetta, G. [Istituto di Astrofisica Spaziale e Fisica Cosmica di Palermo, IASF-Pa/INAF, Palermo (Italy); Belluso, M.; Billotta, S. [Osservatorio Astrofisico di Catania, OACT/INAF, Catania (Italy); Biondo, B. [Istituto di Astrofisica Spaziale e Fisica Cosmica di Palermo, IASF-Pa/INAF, Palermo (Italy); Bonanno, G. [Osservatorio Astrofisico di Catania, OACT/INAF, Catania (Italy); Catalano, O.; Giarrusso, S. [Istituto di Astrofisica Spaziale e Fisica Cosmica di Palermo, IASF-Pa/INAF, Palermo (Italy); Grillo, A. [Osservatorio Astrofisico di Catania, OACT/INAF, Catania (Italy); Impiombato, D.; La Rosa, G.; Maccarone, M.C.; Mangano, A. [Istituto di Astrofisica Spaziale e Fisica Cosmica di Palermo, IASF-Pa/INAF, Palermo (Italy); Marano, D. [Osservatorio Astrofisico di Catania, OACT/INAF, Catania (Italy); Mineo, T.; Segreto, A.; Strazzeri, E. [Istituto di Astrofisica Spaziale e Fisica Cosmica di Palermo, IASF-Pa/INAF, Palermo (Italy); Timpanaro, M.C. [Osservatorio Astrofisico di Catania, OACT/INAF, Catania (Italy)

2013-06-15

UVSiPM is a light detector designed to measure the intensity of electromagnetic radiation in the 320–900 nm wavelength range. It has been developed in the framework of the ASTRI project whose main goal is the design and construction of an end-to-end Small Size class Telescope prototype for the Cherenkov Telescope Array. The UVSiPM instrument is composed by a multipixel Silicon Photo-Multiplier detector unit coupled to an electronic chain working in single photon counting mode with 10 nanosecond double pulse resolution, and by a disk emulator interface card for computer connection. The detector unit of UVSiPM is of the same kind as the ones forming the camera at the focal plane of the ASTRI prototype. Eventually, the UVSiPM instrument can be equipped with a collimator to regulate its angular aperture. UVSiPM, with its peculiar characteristics, will permit to perform several measurements both in lab and on field, allowing the absolute calibration of the ASTRI prototype.

Bubble dynamics and bubble-induced turbulence of a single-bubble chain

Science.gov (United States)

Lee, Joohyoung; Park, Hyungmin

2016-11-01

In the present study, the bubble dynamics and liquid-phase turbulence induced by a chain of bubbles injected from a single nozzle have been experimentally investigated. Using a high-speed two-phase particle image velociemtry, measurements on the bubbles and liquid-phase velocity field are conducted in a transparent tank filled with water, while varying the bubble release frequency from 0.1 to 35 Hz. The tested bubble size ranges between 2.0-3.2 mm, and the corresponding bubble Reynolds number is 590-1100, indicating that it belongs to the regime of path instability. As the release frequency increases, it is found that the global shape of bubble dispersion can be classified into two regimes: from asymmetric (regular) to axisymmetric (irregular). In particular, at higher frequency, the wake vortices of leading bubbles cause an irregular behaviour of the following bubble. For the liquid phase, it is found that a specific trend on the bubble-induced turbulence appears in a strong relation to the above bubble dynamics. Considering this, we try to provide a theoretical model to estimate the liquid-phase turbulence induced by a chain of bubbles. Supported by a Grant funded by Samsung Electronics, Korea.

A uranium-based UO_2"+-Mn"2"+ single-chain magnet assembled trough cation-cation interactions

International Nuclear Information System (INIS)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella; Caciuffo, Roberto; Colineau, Eric; Tuna, Floriana; Magnani, Nicola; Geyer, Arnaud de

2014-01-01

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]_n, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO_2(salen)py][Cp*_2Co] (Cp*=pentamethylcyclopentadienyl) with Cd(NO_3)_2 or Mn(NO_3)_2 in pyridine. The infinite UMn chain displays a high relaxation barrier of 134 ±0.8 K (93 ±0.5 cm"-"1), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T <6 K, with an impressive coercive field of 3.4 T at 2 K. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Purification, crystallization, X-ray diffraction analysis and phasing of an engineered single-chain PvuII restriction endonuclease

International Nuclear Information System (INIS)

Meramveliotaki, Chrysi; Kotsifaki, Dina; Androulaki, Maria; Hountas, Athanasios; Eliopoulos, Elias; Kokkinidis, Michael

2007-01-01

PvuII is the first type II restriction endonuclease to be converted from its wild-type homodimeric form into an enzymatically active single-chain variant. The enzyme was crystallized and phasing was successfully performed by molecular replacement. The restriction endonuclease PvuII from Proteus vulgaris has been converted from its wild-type homodimeric form into the enzymatically active single-chain variant scPvuII by tandemly joining the two subunits through the peptide linker Gly-Ser-Gly-Gly. scPvuII, which is suitable for the development of programmed restriction endonucleases for highly specific DNA cleavage, was purified and crystallized. The crystals diffract to a resolution of 2.35 Å and belong to space group P4 2 , with unit-cell parameters a = b = 101.92, c = 100.28 Å and two molecules per asymmetric unit. Phasing was successfully performed by molecular replacement

Adsorption of a single polymer chain on a surface: effects of the potential range.

Science.gov (United States)

Klushin, Leonid I; Polotsky, Alexey A; Hsu, Hsiao-Ping; Markelov, Denis A; Binder, Kurt; Skvortsov, Alexander M

2013-02-01

We investigate the effects of the range of adsorption potential on the equilibrium behavior of a single polymer chain end-attached to a solid surface. The exact analytical theory for ideal lattice chains interacting with a planar surface via a box potential of depth U and width W is presented and compared to continuum model results and to Monte Carlo (MC) simulations using the pruned-enriched Rosenbluth method for self-avoiding chains on a simple cubic lattice. We show that the critical value U(c) corresponding to the adsorption transition scales as W(-1/ν), where the exponent ν=1/2 for ideal chains and ν≈3/5 for self-avoiding walks. Lattice corrections for finite W are incorporated in the analytical prediction of the ideal chain theory U(c)≈(π(2)/24)(W+1/2)(-2) and in the best-fit equation for the MC simulation data U(c)=0.585(W+1/2)(-5/3). Tail, loop, and train distributions at the critical point are evaluated by MC simulations for 1≤W≤10 and compared to analytical results for ideal chains and with scaling theory predictions. The behavior of a self-avoiding chain is remarkably close to that of an ideal chain in several aspects. We demonstrate that the bound fraction θ and the related properties of finite ideal and self-avoiding chains can be presented in a universal reduced form: θ(N,U,W)=θ(NU(c),U/U(c)). By utilizing precise estimations of the critical points we investigate the chain length dependence of the ratio of the normal and lateral components of the gyration radius. Contrary to common expectations this ratio attains a limiting universal value /=0.320±0.003 only at N~5000. Finite-N corrections for this ratio turn out to be of the opposite sign for W=1 and for W≥2. We also study the N dependence of the apparent crossover exponent φ(eff)(N). Strong corrections to scaling of order N(-0.5) are observed, and the extrapolated value φ=0.483±0.003 is found for all values of W. The strong correction to scaling effects found here explain why

[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.

Comparison of light out-coupling enhancements in single-layer blue-phosphorescent organic light emitting diodes using small-molecule or polymer hosts

International Nuclear Information System (INIS)

Chang, Yung-Ting; Liu, Shun-Wei; Yuan, Chih-Hsien; Lee, Chih-Chien; Ho, Yu-Hsuan; Wei, Pei-Kuen; Chen, Kuan-Yu; Lee, Yi-Ting; Wu, Min-Fei; Chen, Chin-Ti; Wu, Chih-I

2013-01-01

Single-layer blue phosphorescence organic light emitting diodes (OLEDs) with either small-molecule or polymer hosts are fabricated using solution process and the performances of devices with different hosts are investigated. The small-molecule device exhibits luminous efficiency of 14.7 cd/A and maximum power efficiency of 8.39 lm/W, which is the highest among blue phosphorescence OLEDs with single-layer solution process and small molecular hosts. Using the same solution process for all devices, comparison of light out-coupling enhancement, with brightness enhancement film (BEF), between small-molecule and polymer based OLEDs is realized. Due to different dipole orientation and anisotropic refractive index, polymer-based OLEDs would trap less light than small molecule-based OLEDs internally, about 37% better based simulation results. In spite of better electrical and spectroscopic characteristics, including ambipolar characteristics, higher carrier mobility, higher photoluminescence quantum yield, and larger triplet state energy, the overall light out-coupling efficiency of small molecule-based devices is worse than that of polymer-based devices without BEF. However, with BEF for light out-coupling enhancement, the improved ratio in luminous flux and luminous efficiency for small molecule based device is 1.64 and 1.57, respectively, which are significantly better than those of PVK (poly-9-vinylcarbazole) devices. In addition to the theoretical optical simulation, the experimental data also confirm the origins of differential light-outcoupling enhancement. The maximum luminous efficiency and power efficiency are enhanced from 14.7 cd/A and 8.39 lm/W to 23 cd/A and 13.2 lm/W, respectively, with laminated BEF, which are both the highest so far for single-layer solution-process blue phosphorescence OLEDs with small molecule hosts

Comparison of light out-coupling enhancements in single-layer blue-phosphorescent organic light emitting diodes using small-molecule or polymer hosts

Energy Technology Data Exchange (ETDEWEB)

Chang, Yung-Ting [Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, Taiwan (China); Department of Electrical Engineering, Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan 10617, Taiwan (China); Liu, Shun-Wei [Department of Electronic Engineering, Mingchi University of Technology, New Taipei, Taiwan 24301, Taiwan (China); Yuan, Chih-Hsien; Lee, Chih-Chien [Department of Electronic Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan 10607, Taiwan (China); Ho, Yu-Hsuan; Wei, Pei-Kuen [Research Center for Applied Science Academia Sinica, Taipei, Taiwan 11527, Taiwan (China); Chen, Kuan-Yu [Chilin Technology Co., LTD, Tainan City, Taiwan 71758, Taiwan (China); Lee, Yi-Ting; Wu, Min-Fei; Chen, Chin-Ti, E-mail: cchen@chem.sinica.edu.tw, E-mail: chihiwu@cc.ee.ntu.edu.tw [Institute of Chemistry, Academia Sinica, Taipei, Taiwan 11529, Taiwan (China); Wu, Chih-I, E-mail: cchen@chem.sinica.edu.tw, E-mail: chihiwu@cc.ee.ntu.edu.tw [Department of Electrical Engineering, Graduate Institute of Photonics and Optoelectronics, National Taiwan University, Taipei, Taiwan 10617, Taiwan (China)

2013-11-07

Single-layer blue phosphorescence organic light emitting diodes (OLEDs) with either small-molecule or polymer hosts are fabricated using solution process and the performances of devices with different hosts are investigated. The small-molecule device exhibits luminous efficiency of 14.7 cd/A and maximum power efficiency of 8.39 lm/W, which is the highest among blue phosphorescence OLEDs with single-layer solution process and small molecular hosts. Using the same solution process for all devices, comparison of light out-coupling enhancement, with brightness enhancement film (BEF), between small-molecule and polymer based OLEDs is realized. Due to different dipole orientation and anisotropic refractive index, polymer-based OLEDs would trap less light than small molecule-based OLEDs internally, about 37% better based simulation results. In spite of better electrical and spectroscopic characteristics, including ambipolar characteristics, higher carrier mobility, higher photoluminescence quantum yield, and larger triplet state energy, the overall light out-coupling efficiency of small molecule-based devices is worse than that of polymer-based devices without BEF. However, with BEF for light out-coupling enhancement, the improved ratio in luminous flux and luminous efficiency for small molecule based device is 1.64 and 1.57, respectively, which are significantly better than those of PVK (poly-9-vinylcarbazole) devices. In addition to the theoretical optical simulation, the experimental data also confirm the origins of differential light-outcoupling enhancement. The maximum luminous efficiency and power efficiency are enhanced from 14.7 cd/A and 8.39 lm/W to 23 cd/A and 13.2 lm/W, respectively, with laminated BEF, which are both the highest so far for single-layer solution-process blue phosphorescence OLEDs with small molecule hosts.

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

Conjugated Polymer Chains Confined in Vertical Nanocylinders of a Block-Copolymer Film: Preparation, Characterization, and Optoelectronic Function

KAUST Repository

Dong, Ban Xuan; Honmou, Yoshihiro; Komiyama, Hideaki; Furumaki, Shu; Iyoda, Tomokazu; Vacha, Martin

2013-01-01

Hybrid materials composed of phase-separated block copolymer films and conjugated polymers of the phenylenevinylene family (PPV) are prepared. The PPV chains are embedded in vertical cylinders of nanometer diameter in the block-copolymer films. The cylinders span continuously the whole film thickness of 70 nm. Incorporation of the PPV chains into the one-dimensional cylinders leads to modified photoluminescence spectra and to large absorption anisotropy. The hybrid films show electroluminescence from the PPV chains in a simple light-emitting device at minute doping concentrations, and also exhibit a factor of 19 increase in electron transport efficiency along the single PPV chains. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Conjugated Polymer Chains Confined in Vertical Nanocylinders of a Block-Copolymer Film: Preparation, Characterization, and Optoelectronic Function

KAUST Repository

Dong, Ban Xuan

2013-01-15

Hybrid materials composed of phase-separated block copolymer films and conjugated polymers of the phenylenevinylene family (PPV) are prepared. The PPV chains are embedded in vertical cylinders of nanometer diameter in the block-copolymer films. The cylinders span continuously the whole film thickness of 70 nm. Incorporation of the PPV chains into the one-dimensional cylinders leads to modified photoluminescence spectra and to large absorption anisotropy. The hybrid films show electroluminescence from the PPV chains in a simple light-emitting device at minute doping concentrations, and also exhibit a factor of 19 increase in electron transport efficiency along the single PPV chains. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Simultaneous live cell imaging using dual FRET sensors with a single excitation light.

Directory of Open Access Journals (Sweden)

Yusuke Niino

Full Text Available Fluorescence resonance energy transfer (FRET between fluorescent proteins is a powerful tool for visualization of signal transduction in living cells, and recently, some strategies for imaging of dual FRET pairs in a single cell have been reported. However, these necessitate alteration of excitation light between two different wavelengths to avoid the spectral overlap, resulting in sequential detection with a lag time. Thus, to follow fast signal dynamics or signal changes in highly motile cells, a single-excitation dual-FRET method should be required. Here we reported this by using four-color imaging with a single excitation light and subsequent linear unmixing to distinguish fluorescent proteins. We constructed new FRET sensors with Sapphire/RFP to combine with CFP/YFP, and accomplished simultaneous imaging of cAMP and cGMP in single cells. We confirmed that signal amplitude of our dual FRET measurement is comparable to of conventional single FRET measurement. Finally, we demonstrated to monitor both intracellular Ca(2+ and cAMP in highly motile cardiac myocytes. To cancel out artifacts caused by the movement of the cell, this method expands the applicability of the combined use of dual FRET sensors for cell samples with high motility.

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.

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

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

Single-photon three-qubit quantum logic using spatial light modulators.

Science.gov (United States)

Kagalwala, Kumel H; Di Giuseppe, Giovanni; Abouraddy, Ayman F; Saleh, Bahaa E A

2017-09-29

The information-carrying capacity of a single photon can be vastly expanded by exploiting its multiple degrees of freedom: spatial, temporal, and polarization. Although multiple qubits can be encoded per photon, to date only two-qubit single-photon quantum operations have been realized. Here, we report an experimental demonstration of three-qubit single-photon, linear, deterministic quantum gates that exploit photon polarization and the two-dimensional spatial-parity-symmetry of the transverse single-photon field. These gates are implemented using a polarization-sensitive spatial light modulator that provides a robust, non-interferometric, versatile platform for implementing controlled unitary gates. Polarization here represents the control qubit for either separable or entangling unitary operations on the two spatial-parity target qubits. Such gates help generate maximally entangled three-qubit Greenberger-Horne-Zeilinger and W states, which is confirmed by tomographical reconstruction of single-photon density matrices. This strategy provides access to a wide range of three-qubit states and operations for use in few-qubit quantum information processing protocols.Photons are essential for quantum information processing, but to date only two-qubit single-photon operations have been realized. Here the authors demonstrate experimentally a three-qubit single-photon linear deterministic quantum gate by exploiting polarization along with spatial-parity symmetry.

Early recognition is important when multiple magnets masquerade as a single chain after foreign body ingestion

Directory of Open Access Journals (Sweden)

Auriel August

2016-10-01

Full Text Available Ingestions of multiple magnets can lead to serious damage to the gastrointestinal tract. Moreover, these foreign bodies can take deceptive shapes such as single chains which may mislead clinicians. We report the case of a ten-year-old boy who swallowed 33 magnets, the most yet reported, which took on the appearance of a single loop in the stomach, while actually being located in the stomach, small bowel, and colon. Early recognition and prompt intervention are necessary to avoid complications of this foreign body misadventure.

Phase transitions of single polymer chains and of polymer solutions: insights from Monte Carlo simulations

International Nuclear Information System (INIS)

Binder, K; Paul, W; Strauch, T; Rampf, F; Ivanov, V; Luettmer-Strathmann, J

2008-01-01

The statistical mechanics of flexible and semiflexible macromolecules is distinct from that of small molecule systems, since the thermodynamic limit can also be approached when the number of (effective) monomers of a single chain (realizable by a polymer solution in the dilute limit) is approaching infinity. One can introduce effective attractive interactions into a simulation model for a single chain such that a swollen coil contracts when the temperature is reduced, until excluded volume interactions are effectively canceled by attractive forces, and the chain conformation becomes almost Gaussian at the theta point. This state corresponds to a tricritical point, as the renormalization group theory shows. Below the theta temperature a fluid globule is predicted (at nonzero concentration then phase separation between dilute and semidilute solutions occurs), while at still lower temperature a transition to a solid phase (crystal or glass) occurs. Monte Carlo simulations have shown, however, that the fluid globule phase may become suppressed, when the range of the effective attractive forces becomes too short, with the result that a direct (ultimately first-order) transition from the swollen coil to the solid occurs. This behavior is analogous to the behavior of colloidal particles with a very short range of attractive forces, where liquid-vapor-type phase separation may be suppressed. Analogous first-order transitions from swollen coils to dense rodlike or toroidal structures occur for semiflexible polymers. Finally, the modifications of the behavior discussed when the polymers are adsorbed at surfaces are also mentioned, and possible relations to wetting behavior of polymer solutions are addressed.

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.

First principles studies of the electronic properties and catalytic activity of single-walled carbon nanotube doped with Pt clusters and chains

International Nuclear Information System (INIS)

Hayes, Kayla E.; Lee, Hee-Seung

2012-01-01

Highlights: ► Electronic and magnetic properties of (5, 5)-SWNT doped with Pt clusters and chains. ► Pt-doping can change metallic (5, 5)-SWNT to semiconducting CNT. ► Oxygen adsorption on Pt-doped (5, 5)-SWNT is barrierless process. ► Pt-doping reduces the activation barrier of oxygen dissociation reaction. ► Adsorbed oxygen has 2 O 2 - – character. - Abstract: We report the results of density functional theory calculations on the electronic structures, geometrical parameters, and magnetic properties of a wide variety of Pt clusters/chains adsorbed on metallic (5,5) single-walled carbon nanotube (SWNT). It was found that the electronic band structures of Pt/CNT systems are very sensitive to the small changes in the geometries of Pt clusters and chains. In some cases, metallic (5, 5)-SWNT becomes a small-gap semiconducting nanotube with adsorbed Pt clusters and chains. We also investigated the dissociation of molecular oxygen on the (5, 5)-SWNT doped with a single Pt atom via the nudged elastic band (NEB) method. The NEB results showed that the activation barrier is lowered even with a single Pt atom compared to that of pristine SWNT. It was found that the electronic structure of molecular oxygen adsorbed on Pt-doped CNT resembles that of 2 O 2 - , which should facilitate the dissociation process.

Optimal Decisions in a Single-Period Supply Chain with Price-Sensitive Random Demand under a Buy-Back Contract

Directory of Open Access Journals (Sweden)

Feng Wang

2014-01-01

Full Text Available This paper studies a single-period supply chain with a buy-back contract under a Stackelberg game model, in which the supplier (leader decides on the wholesale price, and the retailer (follower responds to determine the retail price and the order quantity. We analytically investigate the decentralized retailer’s optimal decision. Our results demonstrate that the retailer has a unique optimal simultaneous decision on the retail price and the order quantity, under a mild restriction on the demand distribution. Moreover, as it can be shown that the decentralized supply chain facing price-sensitive random demand cannot be coordinated with buy-back contract, we propose a scheme for the system to achieve Pareto-improvement. Theoretical analysis suggests that there exists a unique Pareto-equilibrium for the supply chain. In particular, when the Pareto-equilibrium is reached, the supply chain is coordinated. Numerical experiments confirm our results.

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...

Single component Mn-doped perovskite-related CsPb2ClxBr5-x nanoplatelets with a record white light quantum yield of 49%: a new single layer color conversion material for light-emitting diodes.

Science.gov (United States)

Wu, Hao; Xu, Shuhong; Shao, Haibao; Li, Lang; Cui, Yiping; Wang, Chunlei

2017-11-09

Single component nanocrystals (NCs) with white fluorescence are promising single layer color conversion media for white light-emitting diodes (LED) because the undesirable changes of chromaticity coordinates for the mixture of blue, green and red emitting NCs can be avoided. However, their practical applications have been hindered by the relative low photoluminescence (PL) quantum yield (QY) for traditional semiconductor NCs. Though Mn-doped perovskite nanocube is a potential candidate, it has been unable to realize a white-light emission to date. In this work, the synthesis of Mn-doped 2D perovskite-related CsPb 2 Cl x Br 5-x nanoplatelets with a pure white emission from a single component is reported. Unlike Mn-doped perovskite nanocubes with insufficient energy transfer efficiency, the current reported Mn-doped 2D perovskite-related CsPb 2 Cl x Br 5-x nanoplatelets show a 10 times higher energy transfer efficiency from perovskite to Mn impurities at the required emission wavelengths (about 450 nm for perovskite emission and 580 nm for Mn emission). As a result, the Mn/perovskite dual emission intensity ratio surprisingly elevates from less than 0.25 in case of Mn-doped nanocubes to 0.99 in the current Mn-doped CsPb 2 Cl x Br 5-x nanoplatelets, giving rise to a pure white light emission with Commission Internationale de l'Eclairage (CIE) color coordinates of (0.35, 0.32). More importantly, the highest PL QY for Mn-doped perovskite-related CsPb 2 Cl x Br 5-x nanoplatelets is up to 49%, which is a new record for white-emitting nanocrystals with single component. These highly luminescent nanoplatelets can be blended with polystyrene (PS) without changing the white light emission but dramatically improving perovskite stability. The perovskite-PS composites are available not only as a good solution processable coating material for assembling LED, but also as a superior conversion material for achieving white light LED with a single conversion layer.

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.

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.

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

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.

Conformation of single block copolymer chain in two-dimensional microphase-separated structure studied by scanning near-field optical microscopy.

Science.gov (United States)

Sekine, Ryojun; Aoki, Hiroyuki; Ito, Shinzaburo

2009-05-21

The localization and orientation of the symmetric diblock copolymer chain in a quasi-two-dimensional microphase-separated structure were studied by scanning near-field optical microscopy (SNOM). In the monolayer of poly(isobutyl methacrylate)-block-poly(octadecyl methacrylate) (PiBMA-b-PODMA), the individual PiBMA subchains were directly observed by SNOM, and the center of mass (CM) and orientational angle relative to the phase interface were examined at the single chain level. It was found that the position of the CM and the orientation of the PiBMA subchain in the lamellar structure were dependent on the curvature of the PiBMA/PODMA interface. As the interface was bent toward the objective chain, the block chain preferred the CM position closer to the domain center, and the conformation was strongly oriented perpendicularly to the domain interface. With increase of the curvature, the steric hindrance among the block chain increases, resulting in the stretched conformation.

Electrical contacts to nanorod networks at different length scales: From macroscale ensembles to single nanorod chains

KAUST Repository

Lavieville, Romain; Zhang, Yang; Di Fabrizio, Enzo M.; Krahne, Roman

2013-01-01

The nature of metal-semiconductor interfaces at the nanoscale is an important issue in micro- and nanoelectronic engineering. The study of charge transport through chains of CdSe semiconductor nanorods linked by Au particles represents an ideal model system for this matter, because the metal semiconductor interface is an intrinsic feature of the nanosystem. Here we show the controlled fabrication of all-inorganic hybrid metal-semiconductor networks with different size, in which the semiconductor nanorods are linked by Au domains at their tips. We demonstrate different approaches to selectively contact the networks and single nanorod chains with planar electrodes, and we investigate their charge transport at room temperature. © 2013 Elsevier B.V. All rights reserved.

Electrical contacts to nanorod networks at different length scales: From macroscale ensembles to single nanorod chains

KAUST Repository

Lavieville, Romain

2013-11-01

The nature of metal-semiconductor interfaces at the nanoscale is an important issue in micro- and nanoelectronic engineering. The study of charge transport through chains of CdSe semiconductor nanorods linked by Au particles represents an ideal model system for this matter, because the metal semiconductor interface is an intrinsic feature of the nanosystem. Here we show the controlled fabrication of all-inorganic hybrid metal-semiconductor networks with different size, in which the semiconductor nanorods are linked by Au domains at their tips. We demonstrate different approaches to selectively contact the networks and single nanorod chains with planar electrodes, and we investigate their charge transport at room temperature. © 2013 Elsevier B.V. All rights reserved.

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...

Escherichia coli surface display of single-chain antibody VRC01 against HIV-1 infection

International Nuclear Information System (INIS)

Wang, Lin-Xu; Mellon, Michael; Bowder, Dane; Quinn, Meghan; Shea, Danielle; Wood, Charles; Xiang, Shi-Hua

2015-01-01

Human immunodeficiency virus type 1 (HIV-1) transmission and infection occur mainly via the mucosal surfaces. The commensal bacteria residing in these surfaces can potentially be employed as a vehicle for delivering inhibitors to prevent HIV-1 infection. In this study, we have employed a bacteria-based strategy to display a broadly neutralizing antibody VRC01, which could potentially be used to prevent HIV-1 infection. The VRC01 antibody mimics CD4-binding to gp120 and has broadly neutralization activities against HIV-1. We have designed a construct that can express the fusion peptide of the scFv-VRC01 antibody together with the autotransporter β-barrel domain of IgAP gene from Neisseria gonorrhoeae, which enabled surface display of the antibody molecule. Our results indicate that the scFv-VRC01 antibody molecule was displayed on the surface of the bacteria as demonstrated by flow cytometry and immunofluorescence microscopy. The engineered bacteria can capture HIV-1 particles via surface-binding and inhibit HIV-1 infection in cell culture. - Highlights: • Designed single-chain VRC01 antibody was demonstrated to bind HIV-1 envelope gp120. • Single-chain VRC01 antibody was successfully displayed on the surface of E. coli. • Engineered bacteria can absorb HIV-1 particles and prevent HIV-1 infection in cell culture

End-anchored polymers in good solvents from the single chain limit to high anchoring densities.

Science.gov (United States)

Whitmore, Mark D; Grest, Gary S; Douglas, Jack F; Kent, Michael S; Suo, Tongchuan

2016-11-07

An increasing number of applications utilize grafted polymer layers to alter the interfacial properties of solid substrates, motivating refinement in our theoretical understanding of such layers. To assess existing theoretical models of them, we have investigated end-anchored polymer layers over a wide range of grafting densities, σ, ranging from a single chain to high anchoring density limits, chain lengths ranging over two orders of magnitude, for very good and marginally good solvent conditions. We compare Monte Carlo and molecular dynamics simulations, numerical self-consistent field calculations, and experimental measurements of the average layer thickness, h, with renormalization group theory, the Alexander-de Gennes mushroom theory, and the classical brush theory. Our simulations clearly indicate that appreciable inter-chain interactions exist at all simulated areal anchoring densities so that there is no mushroom regime in which the layer thickness is independent of σ. Moreover, we find that there is no high coverage regime in which h follows the predicted scaling, h ∼ Nσ 1/3 , for classical polymer brushes either. Given that no completely adequate analytic theory seems to exist that spans wide ranges of N and σ, we applied scaling arguments for h as a function of a suitably defined reduced anchoring density, defined in terms of the solution radius of gyration of the polymer chains and N. We find that such a scaling approach enables a smooth, unified description of h in very good solvents over the full range of anchoring density and chain lengths, although this type of data reduction does not apply to marginal solvent quality conditions.

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.

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...

Effective single chain antibody (scFv) concentrations in vivo via adenoviral vector mediated expression of secretory scFv

NARCIS (Netherlands)

Arafat, WO; Gomez-Navarro, J; Buchsbaum, DJ; Xiang, J; Casado, E; Barker, SD; Mahasreshti, PJ; Haisma, HJ; Barnes, MN; Siegal, GP; Alvarez, RD; Hemminki, A; Nettelbeck, DM; Curiel, DT

Single chain antibodies (scFv) represent powerful interventional agents for the achievement of targeted therapeutics. The practical utility of these agents have been limited, however, by difficulties related to production of recombinant scFv and the achievement of effective and sustained levels of

Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

Science.gov (United States)

Sun, Xiaoming; Saito, Masumichi; Sato, Yoshinori; Chikata, Takayuki; Naruto, Takuya; Ozawa, Tatsuhiko; Kobayashi, Eiji; Kishi, Hiroyuki; Muraguchi, Atsushi; Takiguchi, Masafumi

2012-01-01

T-cell receptor (TCR) α/β chains are expressed on the surface of CD8(+) T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+) subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1) chimeric rearrangements of TCRδ-α, (2) control of TCRα/β transcription with multiple transcriptional initiation sites, (3) altered utilization of TCRα/β chains in CD8(+) subsets, and (4) strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+) T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

A new approach to sum frequency generation of single-frequency blue light in a coupled ring cavity

DEFF Research Database (Denmark)

Jensen, Ole Bjarlin; Petersen, Paul Michael

2014-01-01

We present a generic approach for the generation of tunable single-frequency light and demonstrate generation of more than 300 mW tunable light around 460 nm. One tapered diode laser is operated in a coupled ring cavity containing the nonlinear crystal and another tapered diode laser is sent thro...... through the nonlinear crystal in a single pass. A high conversion efficiency of more than 25 % of the single-pass laser is enabled by the high circulating power in the coupled cavity. The system is entirely self-stabilized with no need for electronic locking....

Evidence for single-chain magnet behavior in a Mn(III)-Ni(II) chain designed with high spin magnetic units: a route to high temperature metastable magnets.

Science.gov (United States)

Clérac, Rodolphe; Miyasaka, Hitoshi; Yamashita, Masahiro; Coulon, Claude

2002-10-30

We herein present the synthesis, crystal structure, and magnetic properties of a new heterometallic chain of MnIII and NiII ions, [Mn2(saltmen)2Ni(pao)2(py)2](ClO4)2 (1) (saltmen2- = N,N'-(1,1,2,2-tetramethylethylene) bis(salicylideneiminate) and pao- = pyridine-2-aldoximate). The crystal structure of 1 was investigated by X-ray crystallographic analysis: compound 1 crystallized in monoclinic, space group C2/c (No. 15) with a = 21.140(3) A, b = 15.975(1) A, c = 18.6212(4) A, beta = 98.0586(4) degrees , V = 6226.5(7) A3, and Z = 4. This compound consists of two fragments, the out-of-plane dimer [Mn2(saltmen)2]2+ as a coordination acceptor building block and the neutral mononuclear unit [Ni(pao)2(py)2] as a coordination donor building block, forming an alternating chain having the repeating unit [-Mn-(O)2-Mn-ON-Ni-NO-]n. In the crystal structure, each chain is well separated with a minimum intermetallic distance between Mn and Ni ions of 10.39 A and with the absence of interchain pi overlaps between organic ligands. These features ensure a good magnetic isolation of the chains. The dc and ac magnetic measurements were performed on both the polycrystalline sample and the aligned single crystals of 1. Above 30 K, the magnetic susceptibility of this one-dimensional compound was successfully described in a mean field approximation as an assembly of trimers (Mn...Ni...Mn) with a NiII...MnIII antiferromagnetic interaction (J = -21 K) connected through a ferromagnetic MnIII...MnIII interaction (J'). However, the mean field theory fails to describe the magnetic behavior below 30 K emphasizing the one-dimensional magnetic character of the title compound. Between 5 and 15 K, the susceptibility in the chain direction was fitted to a one-dimensional Ising model leading to the same value of J'. Hysteresis loops are observed below 3.5 K, indicating a magnet-type behavior. In the same range of temperature, combined ac and dc measurements show a slow relaxation of the magnetization

From Animaculum to single molecules: 300 years of the light microscope

Science.gov (United States)

Wollman, Adam J. M.; Nudd, Richard; Hedlund, Erik G.; Leake, Mark C.

2015-01-01

Although not laying claim to being the inventor of the light microscope, Antonj van Leeuwenhoek (1632–1723) was arguably the first person to bring this new technological wonder of the age properly to the attention of natural scientists interested in the study of living things (people we might now term ‘biologists’). He was a Dutch draper with no formal scientific training. From using magnifying glasses to observe threads in cloth, he went on to develop over 500 simple single lens microscopes (Baker & Leeuwenhoek 1739 Phil. Trans. 41, 503–519. (doi:10.1098/rstl.1739.0085)) which he used to observe many different biological samples. He communicated his finding to the Royal Society in a series of letters (Leeuwenhoek 1800 The select works of Antony Van Leeuwenhoek, containing his microscopical discoveries in many of the works of nature, vol. 1) including the one republished in this edition of Open Biology. Our review here begins with the work of van Leeuwenhoek before summarizing the key developments over the last ca 300 years, which has seen the light microscope evolve from a simple single lens device of van Leeuwenhoek's day into an instrument capable of observing the dynamics of single biological molecules inside living cells, and to tracking every cell nucleus in the development of whole embryos and plants. PMID:25924631

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.

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.

Nanostructured current-confined single quantum dot light-emitting diode at 1300 nm

NARCIS (Netherlands)

Monat, C.; Alloing, B.; Zinoni, C.; Li, L.; Fiore, A.

2006-01-01

A novel light-emitting-diode structure is demonstrated, which relies on nanoscale current injection through an oxide aperture to achieve selective excitation of single InAs/GaAs quantum dots. Low-temp. electroluminescence spectra evidence discrete narrow lines around 1300 nm (line width ~ 75 micro

Polymorphism of myofibrillar proteins of rabbit skeletal-muscle fibres. An electrophoretic study of single fibres.

OpenAIRE

Salviati, G; Betto, R; Danieli Betto, D

1982-01-01

Rabbit predominantly fast-twitch-fibre and predominantly slow-twitch-fibre skeletal muscles of the hind limbs, the psoas, the diaphragm and the masseter muscles were fibre-typed by one-dimensional polyacrylamide-gel electrophoresis of the myofibrillar proteins of chemically skinned single fibres. Investigation of the distribution of fast-twitch-fibre and slow-twitch-fibre isoforms of myosin light chains and the type of myosin heavy chains, based on peptide 'maps' published in Cleveland. Fisch...

Contaminant transport in fractured porous media: analytical solution for a two-member decay chain in a single fracture

International Nuclear Information System (INIS)

Sudicky, E.A.; Frind, E.O.

1984-01-01

An analytical solution is presented for the problem of radionuclide chain decay during transport through a discrete fracture situated in a porous rock matrix. The solution takes into account advection along the fracture, molecular diffusion from the fracture to the porous matrix, adsorption on the fracture face, adsorption in the rock matrix, and radioactive decay. The solution for the daughter product is in the form of a double integral which is evaluated by Gauss-Legendre quadrature. Results show that the daughter product tends to advance ahead of the parent nuclide even when the half-life of the parent is larger. This is attributed to the effect of chain decay in the matrix, which tends to reduce the diffusive loss of the daughter along the fracture. The examples also demonstrate that neglecting the parent nuclide and modeling its daughter as a single species can result in significant overestimation of arrival times at some point along the fracture. Although the analytical solution is restricted to a two-member chain for practical reasons, it represents a more realistic description of nuclide transport along a fracture than available single-species models. The solution may be of use for application to other contaminants undergoing different types of first-order transformation reactions

Ground-state phase diagram of an (S, S') = (1, 2) spin-alternating chain with competing single-ion anisotropies

International Nuclear Information System (INIS)

Tonegawa, T; Okamoto, K; Sakai, T; Kaburagi, M

2009-01-01

Employing various numerical methods, we determine the ground-state phase diagram of an (S, S') = (1, 2) spin-alternating chain with antiferromagnetic nearest-neighboring exchange interactions and uniaxial single-ion anisotropies. The resulting phase diagram consists of eight kinds of phases including two phases which accompany the spontaneous breaking of the translational symmetry and a ferrimagnetic phase in which the ground-state magnetization varies continuously with the uniaxial single-ion anisotropy constants for the S=1 and S =2 spins. The appearance of these three phases is attributed to the competition between the uniaxial single-ion anisotropies of both spins.

Design principles of natural light-harvesting as revealed by single molecule spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Krüger, T.P.J., E-mail: tjaart.kruger@up.ac.za [Department of Physics, University of Pretoria, Private bag X20, Hatfield 0028 (South Africa); Grondelle, R. van [Department of Physics and Astronomy, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam (Netherlands)

2016-01-01

Biology offers a boundless source of adaptation, innovation, and inspiration. A wide range of photosynthetic organisms exist that are capable of harvesting solar light in an exceptionally efficient way, using abundant and low-cost materials. These natural light-harvesting complexes consist of proteins that strongly bind a high density of chromophores to capture solar photons and rapidly transfer the excitation energy to the photochemical reaction centre. The amount of harvested light is also delicately tuned to the level of solar radiation to maintain a constant energy throughput at the reaction centre and avoid the accumulation of the products of charge separation. In this Review, recent developments in the understanding of light-harvesting by plants will be discussed, based on results obtained from single molecule spectroscopy studies. Three design principles of the main light-harvesting antenna of plants will be highlighted: (a) fine, photoactive control over the intrinsic protein disorder to efficiently use intrinsically available thermal energy dissipation mechanisms; (b) the design of the protein microenvironment of a low-energy chromophore dimer to control the amount of shade absorption; (c) the design of the exciton manifold to ensure efficient funneling of the harvested light to the terminal emitter cluster.

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.

Terahertz light-emitting graphene-channel transistor toward single-mode lasing

Science.gov (United States)

Yadav, Deepika; Tamamushi, Gen; Watanabe, Takayuki; Mitsushio, Junki; Tobah, Youssef; Sugawara, Kenta; Dubinov, Alexander A.; Satou, Akira; Ryzhii, Maxim; Ryzhii, Victor; Otsuji, Taiichi

2018-03-01

A distributed feedback dual-gate graphene-channel field-effect transistor (DFB-DG-GFET) was fabricated as a current-injection terahertz (THz) light-emitting laser transistor. We observed a broadband emission in a 1-7.6-THz range with a maximum radiation power of 10 μW as well as a single-mode emission at 5.2 THz with a radiation power of 0.1 μW both at 100 K when the carrier injection stays between the lower cutoff and upper cutoff threshold levels. The device also exhibited peculiar nonlinear threshold-like behavior with respect to the current-injection level. The LED-like broadband emission is interpreted as an amplified spontaneous THz emission being transcended to a single-mode lasing. Design constraints on waveguide structures for better THz photon field confinement with higher gain overlapping as well as DFB cavity structures with higher Q factors are also addressed towards intense, single-mode continuous wave THz lasing at room temperature.

A conceptual framework for economic optimization of single hazard surveillance in livestock production chains.

Science.gov (United States)

Guo, Xuezhen; Claassen, G D H; Oude Lansink, A G J M; Saatkamp, H W

2014-06-01

Economic analysis of hazard surveillance in livestock production chains is essential for surveillance organizations (such as food safety authorities) when making scientifically based decisions on optimization of resource allocation. To enable this, quantitative decision support tools are required at two levels of analysis: (1) single-hazard surveillance system and (2) surveillance portfolio. This paper addresses the first level by presenting a conceptual approach for the economic analysis of single-hazard surveillance systems. The concept includes objective and subjective aspects of single-hazard surveillance system analysis: (1) a simulation part to derive an efficient set of surveillance setups based on the technical surveillance performance parameters (TSPPs) and the corresponding surveillance costs, i.e., objective analysis, and (2) a multi-criteria decision making model to evaluate the impacts of the hazard surveillance, i.e., subjective analysis. The conceptual approach was checked for (1) conceptual validity and (2) data validity. Issues regarding the practical use of the approach, particularly the data requirement, were discussed. We concluded that the conceptual approach is scientifically credible for economic analysis of single-hazard surveillance systems and that the practicability of the approach depends on data availability. Copyright © 2014 Elsevier B.V. All rights reserved.

Unbiased analysis of TCRα/β chains at the single-cell level in human CD8+ T-cell subsets.

Directory of Open Access Journals (Sweden)

Xiaoming Sun

Full Text Available T-cell receptor (TCR α/β chains are expressed on the surface of CD8(+ T-cells and have been implicated in antigen recognition, activation, and proliferation. However, the methods for characterization of human TCRα/β chains have not been well established largely because of the complexity of their structures owing to the extensive genetic rearrangements that they undergo. Here we report the development of an integrated 5'-RACE and multiplex PCR method to amplify the full-length transcripts of TCRα/β at the single-cell level in human CD8(+ subsets, including naive, central memory, early effector memory, late effector memory, and effector phenotypic cells. Using this method, with an approximately 47% and 62% of PCR success rate for TCRα and for TCRβ chains, respectively, we were able to analyze more than 1,000 reads of transcripts of each TCR chain. Our comprehensive analysis revealed the following: (1 chimeric rearrangements of TCRδ-α, (2 control of TCRα/β transcription with multiple transcriptional initiation sites, (3 altered utilization of TCRα/β chains in CD8(+ subsets, and (4 strong association between the clonal size of TCRα/β chains and the effector phenotype of CD8(+ T-cells. Based on these findings, we conclude that our method is a useful tool to identify the dynamics of the TCRα/β repertoire, and provides new insights into the study of human TCRα/β chains.

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.

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.

Statistical properties of intensity of partially polarised semiconductor laser light backscattered by a single-mode optical fibre

International Nuclear Information System (INIS)

Alekseev, A E; Potapov, V T; Gorshkov, B G

2015-01-01

We report the results of studying statistical properties of the intensity of partially polarised coherent light backscattered by a single mode optical fibre. An expression is derived for the deviation of the backscattered light intensity depending on the scattering region length, the degree of the light source coherence and the degree of scattered light polarisation. It is shown that the backscattered light in a fibre scattered-light interferometer is partially polarised with the polarisation degree P = 1/3 in the case of external perturbations of the interferometer fibre. (scattering of light)

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.

Membranous Glomerulopathy With Light Chain–Restricted Deposits: A Clinicopathological Analysis of 28 Cases

Directory of Open Access Journals (Sweden)

Alejandro Best Rocha

2017-11-01

Discussion: The majority of MG cases with light chain isotype−restricted deposits lack a recognizable secondary etiology. However, the absence of PLA2R positivity, positive staining for a single IgG subclass, and presence of focal proliferation are worrisome histopathologic features that should prompt a thorough clinical workup to exclude the presence of an underlying LPD.

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.

Reevaluation of the role of nuclear uncertainties in experiments on atomic parity violation with isotopic chains

International Nuclear Information System (INIS)

Derevianko, Andrei; Porsev, Sergey G.

2002-01-01

In light of new data on neutron distributions from experiments with antiprotonic atoms [Trzcinska et al., Phys. Rev. Lett. 87, 082501 (2001)], we reexamine the role of nuclear-structure uncertainties in the interpretation of measurements of parity violation in atoms using chains of isotopes of the same element. With these new nuclear data, we find an improvement in the sensitivity of isotopic chain measurements to 'new physics' beyond the standard model. We compare possible constraints on 'new physics' with the most accurate to date single-isotope probe of parity violation in the Cs atom. We conclude that presently isotopic chain experiments employing atoms with nuclear charges Z < or approx. 50 may result in more accurate tests of the weak interaction

Development of coordination system model on single-supplier multi-buyer for multi-item supply chain with probabilistic demand

Science.gov (United States)

Olivia, G.; Santoso, A.; Prayogo, D. N.

2017-11-01

Nowadays, the level of competition between supply chains is getting tighter and a good coordination system between supply chains members is very crucial in solving the issue. This paper focused on a model development of coordination system between single supplier and buyers in a supply chain as a solution. Proposed optimization model was designed to determine the optimal number of deliveries from a supplier to buyers in order to minimize the total cost over a planning horizon. Components of the total supply chain cost consist of transportation costs, handling costs of supplier and buyers and also stock out costs. In the proposed optimization model, the supplier can supply various types of items to retailers whose item demand patterns are probabilistic. Sensitivity analysis of the proposed model was conducted to test the effect of changes in transport costs, handling costs and production capacities of the supplier. The results of the sensitivity analysis showed a significant influence on the changes in the transportation cost, handling costs and production capacity to the decisions of the optimal numbers of product delivery for each item to the buyers.

Accelerating the coupled-cluster singles and doubles method using the chain-of-sphere approximation

Science.gov (United States)

Dutta, Achintya Kumar; Neese, Frank; Izsák, Róbert

2018-06-01

In this paper, we present a chain-of-sphere implementation of the external exchange term, the computational bottleneck of coupled-cluster calculations at the singles and doubles level. This implementation is compared to standard molecular orbital, atomic orbital and resolution of identity implementations of the same term within the ORCA package and turns out to be the most efficient one for larger molecules, with a better accuracy than the resolution-of-identity approximation. Furthermore, it becomes possible to perform a canonical CC calculation on a tetramer of nucleobases in 17 days, 20 hours.

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...

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

An ATP sensitive light addressable biosensor for extracellular monitoring of single taste receptor cell.

Science.gov (United States)

Wu, Chunsheng; Du, Liping; Zou, Ling; Zhao, Luhang; Wang, Ping

2012-12-01

Adenosine triphosphate (ATP) is considered as the key neurotransmitter in taste buds for taste signal transmission and processing. Measurements of ATP secreted from single taste receptor cell (TRC) with high sensitivity and specificity are essential for investigating mechanisms underlying taste cell-to-cell communications. In this study, we presented an aptamer-based biosensor for the detection of ATP locally secreted from single TRC. ATP sensitive DNA aptamer was used as recognition element and its DNA competitor was served as signal transduction element that was covalently immobilized on the surface of light addressable potentiometric sensor (LAPS). Due to the light addressable capability of LAPS, local ATP secretion from single TRC can be detected by monitoring the working potential shifts of LAPS. The results show this biosensor can detect ATP with high sensitivity and specificity. It is demonstrated this biosensor can effectively detect the local ATP secretion from single TRC responding to tastant mixture. This biosensor could provide a promising new tool for the research of taste cell-to-cell communications as well as for the detection of local ATP secretion from other types of ATP secreting individual cells.

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.

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).

Single-chain magnet features in 1D [MnR4TPP][TCNE] compounds

International Nuclear Information System (INIS)

Balanda, Maria; Tomkowicz, Zbigniew; Rams, Michal; Haase, Wolfgang

2011-01-01

Molecular chains of antiferrimagnetically coupled Mn III -ion (S = 2) and TCNE (tetracyanoethylene) radical moments (s = 1/2 ) show different behaviour depending on group R substituted to TPP (tetraphenylporphyrin) and on the substitution site. The compound with R = F in Ortho position is a Single-Chain Magnet (SCM) with blocking temperature T b = 6.6K, while that with R = F in Meta position shows both blocking (T b = 5.4 K) and magnetic ordering transition (T c = 10 K). For bulky groups R = OC n H 2n+1 , the magnetically ordered phase is observed (T c ∼ 22 K), which does not however prevent slow relaxation at T c of 2 T at 2.3 K is like that of SCM. The frequency dependent AC susceptibility in the superimposed DC field reveals common features of all systems. The energy of intrachain ferromagnetic coupling between effective spin units 3/2, relevant at low temperatures, is determined for all compounds and the interchain dipolar coupling is estimated. It is concluded that slow relaxation is inherent for all quasi one-dimensional compounds and for the magnetically ordered ones shows up in the high enough magnetic field.

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.

Bioaccumulation and Toxicity of Single-Walled Carbon Nanotubes to Benthic Organisms at the Base of the Marine Food Chain

Science.gov (United States)

As the use of single-walled carbon nanotubes (SWNTs) increases over time, so does the potential for environmental release. This research aimed to determine the toxicity, bioavailability, and bioaccumulation of SWNTs in marine benthic organisms at the base of the food chain. The t...

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.

EARLINET Single Calculus Chain - overview on methodology and strategy

Science.gov (United States)

D'Amico, G.; Amodeo, A.; Baars, H.; Binietoglou, I.; Freudenthaler, V.; Mattis, I.; Wandinger, U.; Pappalardo, G.

2015-11-01

In this paper we describe the EARLINET Single Calculus Chain (SCC), a tool for the automatic analysis of lidar measurements. The development of this tool started in the framework of EARLINET-ASOS (European Aerosol Research Lidar Network - Advanced Sustainable Observation System); it was extended within ACTRIS (Aerosol, Clouds and Trace gases Research InfraStructure Network), and it is continuing within ACTRIS-2. The main idea was to develop a data processing chain that allows all EARLINET stations to retrieve, in a fully automatic way, the aerosol backscatter and extinction profiles starting from the raw lidar data of the lidar systems they operate. The calculus subsystem of the SCC is composed of two modules: a pre-processor module which handles the raw lidar data and corrects them for instrumental effects and an optical processing module for the retrieval of aerosol optical products from the pre-processed data. All input parameters needed to perform the lidar analysis are stored in a database to keep track of all changes which may occur for any EARLINET lidar system over the time. The two calculus modules are coordinated and synchronized by an additional module (daemon) which makes the whole analysis process fully automatic. The end user can interact with the SCC via a user-friendly web interface. All SCC modules are developed using open-source and freely available software packages. The final products retrieved by the SCC fulfill all requirements of the EARLINET quality assurance programs on both instrumental and algorithm levels. Moreover, the manpower needed to provide aerosol optical products is greatly reduced and thus the near-real-time availability of lidar data is improved. The high-quality of the SCC products is proven by the good agreement between the SCC analysis, and the corresponding independent manual retrievals. Finally, the ability of the SCC to provide high-quality aerosol optical products is demonstrated for an EARLINET intense observation

Finite-size effects on the dynamic susceptibility of CoPhOMe single-chain molecular magnets in presence of a static magnetic field

Science.gov (United States)

Pini, M. G.; Rettori, A.; Bogani, L.; Lascialfari, A.; Mariani, M.; Caneschi, A.; Sessoli, R.

2011-09-01

The static and dynamic properties of the single-chain molecular magnet Co(hfac)2NITPhOMe (CoPhOMe) (hfac = hexafluoroacetylacetonate, NITPhOMe = 4'-methoxy-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide) are investigated in the framework of the Ising model with Glauber dynamics, in order to take into account both the effect of an applied magnetic field and a finite size of the chains. For static fields of moderate intensity and short chain lengths, the approximation of a monoexponential decay of the magnetization fluctuations is found to be valid at low temperatures; for strong fields and long chains, a multiexponential decay should rather be assumed. The effect of an oscillating magnetic field, with intensity much smaller than that of the static one, is included in the theory in order to obtain the dynamic susceptibility χ(ω). We find that, for an open chain with N spins, χ(ω) can be written as a weighted sum of N frequency contributions, with a sum rule relating the frequency weights to the static susceptibility of the chain. Very good agreement is found between the theoretical dynamic susceptibility and the ac susceptibility measured in moderate static fields (Hdc≤2 kOe), where the approximation of a single dominating frequency for each segment length turns out to be valid. For static fields in this range, data for the relaxation time, τ versus Hdc, of the magnetization of CoPhOMe at low temperature are also qualitatively reproduced by theory, provided that finite-size effects are included.

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.

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.

Structure predictions of two Bauhinia variegata lectins reveal patterns of C-terminal properties in single chain legume lectins.

Science.gov (United States)

Moreira, Gustavo M S G; Conceição, Fabricio R; McBride, Alan J A; Pinto, Luciano da S

2013-01-01

Bauhinia variegata lectins (BVL-I and BVL-II) are single chain lectins isolated from the plant Bauhinia variegata. Single chain lectins undergo post-translational processing on its N-terminal and C-terminal regions, which determines their physiological targeting, carbohydrate binding activity and pattern of quaternary association. These two lectins are isoforms, BVL-I being highly glycosylated, and thus far, it has not been possible to determine their structures. The present study used prediction and validation algorithms to elucidate the likely structures of BVL-I and -II. The program Bhageerath-H was chosen from among three different structure prediction programs due to its better overall reliability. In order to predict the C-terminal region cleavage sites, other lectins known to have this modification were analysed and three rules were created: (1) the first amino acid of the excised peptide is small or hydrophobic; (2) the cleavage occurs after an acid, polar, or hydrophobic residue, but not after a basic one; and (3) the cleavage spot is located 5-8 residues after a conserved Leu amino acid. These rules predicted that BVL-I and -II would have fifteen C-terminal residues cleaved, and this was confirmed experimentally by Edman degradation sequencing of BVL-I. Furthermore, the C-terminal analyses predicted that only BVL-II underwent α-helical folding in this region, similar to that seen in SBA and DBL. Conversely, BVL-I and -II contained four conserved regions of a GS-I association, providing evidence of a previously undescribed X4+unusual oligomerisation between the truncated BVL-I and the intact BVL-II. This is the first report on the structural analysis of lectins from Bauhinia spp. and therefore is important for the characterisation C-terminal cleavage and patterns of quaternary association of single chain lectins.

Heterogeneity of rabbit endogenous pyrogens is not attributable to glycosylated variants of a single polypeptide chain.

OpenAIRE

Murphy, P A; Cebula, T A; Windle, B E

1981-01-01

Rabbit endogenous pyrogens were of about the same molecular size, but showed considerable heterogeneity of their isoelectric points. We attempted to show that this heterogeneity was attributable to variable glycosylation of a single polypeptide chain. When peritoneal exudate cells were stimulated to make pyrogens in the presence of 2-deoxy-D-glucose, there was a relatively trivial suppression of pyrogen release, and analysis by isoelectric focusing showed parallel inhibition of secretion of a...

Schottky junctions on perovskite single crystals: light-modulated dielectric constant and self-biased photodetection

KAUST Repository

Shaikh, Parvez Abdul Ajij

2016-08-16

Schottky junctions formed between semiconductors and metal contacts are ubiquitous in modern electronic and optoelectronic devices. Here we report on the physical properties of Schottky-junctions formed on hybrid perovskite CH3NH3PbBr3 single crystals. It is found that light illumination can significantly increase the dielectric constant of perovskite junctions by 2300%. Furthermore, such Pt/perovskite junctions are used to fabricate self-biased photodetectors. A photodetectivity of 1.4 × 1010 Jones is obtained at zero bias, which increases to 7.1 × 1011 Jones at a bias of +3 V, and the photodetectivity remains almost constant in a wide range of light intensity. These devices also exhibit fast responses with a rising time of 70 μs and a falling time of 150 μs. As a result of the high crystal quality and low defect density, such single-crystal photodetectors show stable performance after storage in air for over 45 days. Our results suggest that hybrid perovskite single crystals provide a new platform to develop promising optoelectronic applications. © 2016 The Royal Society of Chemistry.

White emission from liquid-crystalline copolymers containing oxadiazole moieties in the side chain

Science.gov (United States)

Kawamoto, Masuki; Tsukamoto, Takuji; Kinoshita, Motoi; Ikeda, Tomiki

2006-09-01

A liquid-crystalline polymer in the side chain was synthesized through copolymerization of a bipolar carrier-transporting monomer with a liquid-crystalline monomer containing oxadiazole moieties substituted with trifluoromethyl groups. A single-layer light-emitting diode of indium tin oxide (ITO)/copolymer/MgAg emitted white light with a maximum luminous efficiency of 0.1cd/A. The origin of the white emission in the copolymer is the electroplex between bipolar carrier-transporting moieties and strong electron-withdrawing moieties. Furthermore, a simple multilayer device with configuration of ITO/poly(3,4-ethylenedioxythiophene)/poly(styrenesulfonic acid)/copolymer/MgAg device showed white emission with CIE 1931 chromaticity coordinates (x,y): (0.30, 0.33).

Universal holonomic single quantum gates over a geometric spin with phase-modulated polarized light.

Science.gov (United States)

Ishida, Naoki; Nakamura, Takaaki; Tanaka, Touta; Mishima, Shota; Kano, Hiroki; Kuroiwa, Ryota; Sekiguchi, Yuhei; Kosaka, Hideo

2018-05-15

We demonstrate universal non-adiabatic non-abelian holonomic single quantum gates over a geometric electron spin with phase-modulated polarized light and 93% average fidelity. This allows purely geometric rotation around an arbitrary axis by any angle defined by light polarization and phase using a degenerate three-level Λ-type system in a negatively charged nitrogen-vacancy center in diamond. Since the control light is completely resonant to the ancillary excited state, the demonstrated holonomic gate not only is fast with low power, but also is precise without the dynamical phase being subject to control error and environmental noise. It thus allows pulse shaping for further fidelity.

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

A uranium-based UO{sub 2}{sup +}-Mn{sup 2+} single-chain magnet assembled trough cation-cation interactions

Energy Technology Data Exchange (ETDEWEB)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella [CEA-Grenoble (France). Lab. de Reconnaissance Ionique et Chimie de Coordination; Caciuffo, Roberto; Colineau, Eric [European Commission, Karlsruhe (Germany). Inst. for Transuranium Elements; Tuna, Floriana [Manchester Univ. (United Kingdom). School of Chemistry; Magnani, Nicola [KIT Karlsruhe (Germany). Inst. of Nanotechnology; Geyer, Arnaud de [CEA-Grenoble (France). Service General des Rayons X

2014-01-13

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]{sub n}, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO{sub 2}(salen)py][Cp{sup *}{sub 2}Co] (Cp{sup *}=pentamethylcyclopentadienyl) with Cd(NO{sub 3}){sub 2} or Mn(NO{sub 3}){sub 2} in pyridine. The infinite UMn chain displays a high relaxation barrier of 134±0.8 K (93±0.5 cm{sup -1}), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T<6 K, with an impressive coercive field of 3.4 T at 2 K.

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.

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.

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.

Introduction of a point mutation into an HLA class I single-chain trimer induces enhancement of CTL priming and antitumor immunity

Directory of Open Access Journals (Sweden)

Masanori Matsui

2014-01-01

Full Text Available We previously discovered one particular HLA-A*02:01 mutant that enhanced peptide-specific cytotoxic T lymphocyte (CTL recognition in vitro compared to wild-type HLA-A*02:01. This mutant contains a single amino acid substitution from histidine to leucine at position 74 (H74L that is located in the peptide-binding groove. To investigate the effect of the H74L mutation on the in vivo CTL priming, we took advantage of the technology of the HLA class I single-chain trimer (SCT in which three components involving a peptide, β2 microglobulin and the HLA class I heavy chain are joined together via flexible linkers. We generated recombinant adenovirus expressing SCT comprised influenza A matrix protein (FMP-derived peptide, β2 microglobulin and the H74L heavy chain. HLA-A*02:01 transgenic mice were immunized with the adenovirus, and the induction of peptide-specific CTLs and antitumor immunity was investigated. It was clearly shown that the H74L mutation enabled the HLA-A*02:01 SCT molecule to dramatically enhance both in vivo priming of FMP-specific CTLs and protection against a lethal challenge of tumor cells expressing FMP. These data present the first evidence that a simple point mutation in the HLA class I heavy chain of SCT is beneficial for improving CTL-based immunotherapy and prophylaxis to control tumors.

Detecting and locating light atoms from high-resolution STEM images: The quest for a single optimal design

Energy Technology Data Exchange (ETDEWEB)

Gonnissen, J.; De Backer, A. [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium); Dekker, A.J. den [iMinds-Vision Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); Delft Center for Systems and Control (DCSC), Delft University of Technology, Mekelweg 2, 2628 CD Delft (Netherlands); Sijbers, J. [iMinds-Vision Lab, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk (Belgium); Van Aert, S., E-mail: sandra.vanaert@uantwerpen.be [Electron Microscopy for Materials Science (EMAT), University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp (Belgium)

2016-11-15

In the present paper, the optimal detector design is investigated for both detecting and locating light atoms from high resolution scanning transmission electron microscopy (HR STEM) images. The principles of detection theory are used to quantify the probability of error for the detection of light atoms from HR STEM images. To determine the optimal experiment design for locating light atoms, use is made of the so-called Cramér–Rao Lower Bound (CRLB). It is investigated if a single optimal design can be found for both the detection and location problem of light atoms. Furthermore, the incoming electron dose is optimised for both research goals and it is shown that picometre range precision is feasible for the estimation of the atom positions when using an appropriate incoming electron dose under the optimal detector settings to detect light atoms. - Highlights: • The optimal detector design to detect and locate light atoms in HR STEM is derived. • The probability of error is quantified and used to detect light atoms. • The Cramér–Rao lower bound is calculated to determine the atomic column precision. • Both measures are evaluated and result in the single optimal LAADF detector regime. • The incoming electron dose is optimised for both research goals.

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.

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.

Fidelity of Quantum Teleportation for Single-Mode Squeezed State Light

Institute of Scientific and Technical Information of China (English)

ZHANG Jun-Xiang; XIE Chang-De; PENG Kun-Chi

2005-01-01

@@ The fidelity of quantum teleportation of a single-mode squeezed state of light is calculated based on the general theory of quantum-mechanical measurement in the Schrodinger picture. It is shown that the criterion for the nonclassical state teleportation is different from that for coherent state. F = 1/2 is no longer the rigorous boundary between classical and quantum teleportation for a squeezed state of light. When the quantum entanglement of an Einstein-Podolsky-Rosen (EPR) beam used for teleportation and the parameters of the system are given,the fidelity depends on the squeezing of the input squeezed state. The higher the squeezing is, the smaller the fidelity is, and the lower the classical limitation of fidelity is. The dependence of the optimum gain for teleporting a squeezed vacuum state upon the EPR entanglement is also calculated. The results obtained provide important references for designing experimental systems of teleporting a non-classical state and judging the quality of the teleported quantum state.

Role of light in the mediation of acute effects of a single afternoon ...

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences; Volume 25; Issue 3. Role of light in the mediation of acute effects of a single afternoon melatonin injection on steroidogenic activity of testis in the rat. Saumen K Maitra Arun K Ray. Articles Volume 25 Issue 3 September 2000 pp 253-256 ...

Growth and characterization of air annealing Tb-doped YAG:Ce single crystal for white-light-emitting diode

International Nuclear Information System (INIS)

Gong, Maogao; Xiang, Weidong; Liang, Xiaojuan; Zhong, Jiasong; Chen, Daqin; Huang, Jun; Gu, Guorui; Yang, Cheng; Xiang, Run

2015-01-01

Highlights: • We report preparation of transparent Ce,Tb:YAG single crystal by Czochralski method. • The effect of annealing on Ce,Tb:YAG single crystal had been investigated. • The Ce,Tb:YAG single crystal after annealing exhibited better optical performance. • The Ce,Tb:YAG single crystal could be used as an ideal candidate for WLED. - Abstract: We report the preparation of transparent Ce and Tb co-doped Y 3 Al 5 O 12 single crystal by the Czochralski method. The characterization of the resulting single crystal was accomplished by using X-ray powder diffractometer, scanning electron microscopy and energy dispersive X-ray spectroscopy. Absorption peak of the single crystal at about 460 nm has been obtained from ultraviolet–visible absorption spectrometer and their intensity is changed with different annealing condition. Its optical properties also have been investigated using fluorescence spectrometer. What’s more, its photoelectric parameters were studied by LED fast spectrometer. The constructed single crystal based white-light-emitting diode exhibits a high luminous efficiency of 140.89 lm/W, and a correlated color temperature of 4176 K as well as a color rendering index of 56.7, which reveal the prominent feasibility of the present single crystal material in white-light-emitting diode application

Growth and characterization of air annealing Tb-doped YAG:Ce single crystal for white-light-emitting diode

Energy Technology Data Exchange (ETDEWEB)

Gong, Maogao [College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 (China); Xiang, Weidong, E-mail: xiangweidong001@126.com [College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 (China); Liang, Xiaojuan [College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 (China); Zhong, Jiasong; Chen, Daqin [College of Materials & Environmental Engineering, Hangzhou Dianzi University, Hangzhou 310018 (China); Huang, Jun; Gu, Guorui; Yang, Cheng; Xiang, Run [College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou 325035 (China)

2015-08-05

Highlights: • We report preparation of transparent Ce,Tb:YAG single crystal by Czochralski method. • The effect of annealing on Ce,Tb:YAG single crystal had been investigated. • The Ce,Tb:YAG single crystal after annealing exhibited better optical performance. • The Ce,Tb:YAG single crystal could be used as an ideal candidate for WLED. - Abstract: We report the preparation of transparent Ce and Tb co-doped Y{sub 3}Al{sub 5}O{sub 12} single crystal by the Czochralski method. The characterization of the resulting single crystal was accomplished by using X-ray powder diffractometer, scanning electron microscopy and energy dispersive X-ray spectroscopy. Absorption peak of the single crystal at about 460 nm has been obtained from ultraviolet–visible absorption spectrometer and their intensity is changed with different annealing condition. Its optical properties also have been investigated using fluorescence spectrometer. What’s more, its photoelectric parameters were studied by LED fast spectrometer. The constructed single crystal based white-light-emitting diode exhibits a high luminous efficiency of 140.89 lm/W, and a correlated color temperature of 4176 K as well as a color rendering index of 56.7, which reveal the prominent feasibility of the present single crystal material in white-light-emitting diode application.

Highly efficient single-layer dendrimer light-emitting diodes with balanced charge transport

Science.gov (United States)

Anthopoulos, Thomas D.; Markham, Jonathan P. J.; Namdas, Ebinazar B.; Samuel, Ifor D. W.; Lo, Shih-Chun; Burn, Paul L.

2003-06-01

High-efficiency single-layer-solution-processed green light-emitting diodes based on a phosphorescent dendrimer are demonstrated. A peak external quantum efficiency of 10.4% (35 cd/A) was measured for a first generation fac-tris(2-phenylpyridine) iridium cored dendrimer when blended with 4,4'-bis(N-carbazolyl)biphenyl and electron transporting 1,3,5-tris(2-N-phenylbenzimidazolyl)benzene at 8.1 V. A maximum power efficiency of 12.8 lm/W was measured also at 8.1 V and 550 cd/m2. These results indicate that, by simple blending of bipolar and electron-transporting molecules, highly efficient light-emitting diodes can be made employing a very simple device structure.

Controlled light emission from white organic light-emitting devices with a single blue-emitting host and multiple fluorescent dopants

International Nuclear Information System (INIS)

Chin, Byung Doo; Kim, Jai Kyeong; Park, O Ok

2007-01-01

In this work, we fabricated white organic light-emitting devices (WOLEDs) containing a layered light-emitting region composed of a single blue-emitting host and different fluorescent dopant materials. The effects of varying the dye-doping ratio and emitting layer thickness on the efficiency, lifetime, spectral voltage-dependence and white balance were investigated for devices with a blue/orange stacked layer structure. Addition of a blue host layer doped with a green-emitting dopant, to give a blue/green/orange emitter, resulted in a broadband white spectrum without the need for a charge-blocking interlayer. The composition of blue, green and orange dopants in the host and the thickness of each emitting layer were optimized, resulting in a device efficiency of 9-11 cd A -1 even at a high brightness of 10 000 cd m -2 (achieved at a bias voltage of less than 9 V) with an emission spectrum suitable for lighting applications

Myosin heavy chain composition of single fibres from m. biceps brachii of male body builders

DEFF Research Database (Denmark)

Klitgaard, H; Zhou, M.-Y.; Richter, Erik

1990-01-01

The myosin heavy chain (MHC) composition of single fibres from m. biceps brachii of young sedentary men (28 +/- 0.4 years, mean +/- SE, n = 4) and male body builders (25 +/- 2.0 years, n = 4) was analysed with a sensitive one-dimensional electrophoretic technique. Compared with sedentary men...... expression of MHC isoforms within histochemical type II fibres of human skeletal muscle with body building. Furthermore, in human skeletal muscle differences in expression of MHC isoforms may not always be reflected in the traditional histochemical classification of types I, IIa, IIb and IIc fibres....

Tilted Light Sheet Microscopy with 3D Point Spread Functions for Single-Molecule Super-Resolution Imaging in Mammalian Cells.

Science.gov (United States)

Gustavsson, Anna-Karin; Petrov, Petar N; Lee, Maurice Y; Shechtman, Yoav; Moerner, W E

2018-02-01

To obtain a complete picture of subcellular nanostructures, cells must be imaged with high resolution in all three dimensions (3D). Here, we present tilted light sheet microscopy with 3D point spread functions (TILT3D), an imaging platform that combines a novel, tilted light sheet illumination strategy with engineered long axial range point spread functions (PSFs) for low-background, 3D super localization of single molecules as well as 3D super-resolution imaging in thick cells. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The axial positions of the single molecules are encoded in the shape of the PSF rather than in the position or thickness of the light sheet, and the light sheet can therefore be formed using simple optics. The result is flexible and user-friendly 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validated TILT3D for 3D super-resolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed Tetrapod PSF for fiducial bead tracking and live axial drift correction. We envision TILT3D to become an important tool not only for 3D super-resolution imaging, but also for live whole-cell single-particle and single-molecule tracking.

Tilted light sheet microscopy with 3D point spread functions for single-molecule super-resolution imaging in mammalian cells

Science.gov (United States)

Gustavsson, Anna-Karin; Petrov, Petar N.; Lee, Maurice Y.; Shechtman, Yoav; Moerner, W. E.

2018-02-01

To obtain a complete picture of subcellular nanostructures, cells must be imaged with high resolution in all three dimensions (3D). Here, we present tilted light sheet microscopy with 3D point spread functions (TILT3D), an imaging platform that combines a novel, tilted light sheet illumination strategy with engineered long axial range point spread functions (PSFs) for low-background, 3D super localization of single molecules as well as 3D super-resolution imaging in thick cells. TILT3D is built upon a standard inverted microscope and has minimal custom parts. The axial positions of the single molecules are encoded in the shape of the PSF rather than in the position or thickness of the light sheet, and the light sheet can therefore be formed using simple optics. The result is flexible and user-friendly 3D super-resolution imaging with tens of nm localization precision throughout thick mammalian cells. We validated TILT3D for 3D superresolution imaging in mammalian cells by imaging mitochondria and the full nuclear lamina using the double-helix PSF for single-molecule detection and the recently developed Tetrapod PSF for fiducial bead tracking and live axial drift correction. We envision TILT3D to become an important tool not only for 3D super-resolution imaging, but also for live whole-cell single-particle and single-molecule tracking.

Enhanced visible light photocatalytic performance of polyaniline modified mesoporous single crystal TiO{sub 2} microsphere

Energy Technology Data Exchange (ETDEWEB)

Deng, Yaocheng [College of Environmental Science and Engineering, Hunan University, Changsha, 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Tang, Lin, E-mail: tanglin@hnu.edu.cn [College of Environmental Science and Engineering, Hunan University, Changsha, 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Zeng, Guangming, E-mail: zgming@hnu.edu.cn [College of Environmental Science and Engineering, Hunan University, Changsha, 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Dong, Haoran; Yan, Ming; Wang, Jingjing [College of Environmental Science and Engineering, Hunan University, Changsha, 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China); Hu, Wei [College of Physics and Microelectronics Science, Hunan University, Changsha, 410082 (China); Wang, Jiajia; Zhou, Yaoyu; Tang, Jing [College of Environmental Science and Engineering, Hunan University, Changsha, 410082 (China); Key Laboratory of Environmental Biology and Pollution Control, Hunan University, Ministry of Education, Changsha 410082 (China)

2016-11-30

Highlights: • The mesoporous single crystal microsphere of PANI/MS-TiO{sub 2} improved the light absorption. • The mesoporous structure of MS-TiO{sub 2} can increase the loading amount of PANI. • The synergistic effect between PANI and MS-TiO{sub 2} promoted the separation of charges. • Improved photocatalysis was achieved via PANI modified mesoporous single crystal TiO{sub 2} microsphere. - Abstract: Polyaniline (PANI) modified mesoporous single crystal TiO{sub 2} microsphere (PANI/MS-TiO{sub 2}) with excellent photocatalytic activity was successfully prepared by a simple method of solution evaporation and chemisorption. The X-ray diffraction characterization demonstrated that the whole MS-TiO{sub 2} kept the crystal type of anatase. The nitrogen adsorption-desorption characterization coupled with scanning electron microscopy indicated that the MS-TiO{sub 2} possessed a unique mesoporous structure with high specific surface area, which resulted in the increased load of PANI on the surface of MS-TiO{sub 2} and multiple light reflection in the photocatalyst. The UV–vis diffuse reflectance spectra confirmed that PANI/MS-TiO{sub 2} presented more absorption ability in the visible light range than that of the pristine MS-TiO{sub 2}. The transient photocurrent responses and electrochemical impedance spectroscopy (EIS) indicated the high photo responses and fast photogenerated charge separation efficiency of PANI/MS-TiO{sub 2}. The photocatalytic activity of the PANI/MS-TiO{sub 2} was evaluated by the photodegradation of RhB and MB under visible light irradiation. MS-TiO{sub 2} photocatalyst with different molar ration of PANI had been prepared, and the results showed that the optimal photocatalyst (PANI/MS-TiO{sub 2} (1:40)) exhibited the highest photocatalytic efficiency which is nearly three times as great as that of pristine MS-TiO{sub 2} for the degradation of the RhB and MB under visible light irradiation. The remarkable performance of the PANI

Quantum phase transitions in spin-1 X X Z chains with rhombic single-ion anisotropy

Science.gov (United States)

Ren, Jie; Wang, Yimin; You, Wen-Long

2018-04-01

We explore numerically the inverse participation ratios in the ground state of one-dimensional spin-1 X X Z chains with the rhombic single-ion anisotropy. By employing the techniques of density-matrix renormalization group, effects of the rhombic single-ion anisotropy on various information theoretical measures are investigated, such as the fidelity susceptibility, the quantum coherence, and the entanglement entropy. Their relations with the quantum phase transitions are also analyzed. The phase transitions from the Y -Néel phase to the large-Ex or the Haldane phase can be well characterized by the fidelity susceptibility. The second-order derivative of the ground-state energy indicates all the transitions are of second order. We also find that the quantum coherence, the entanglement entropy, the Schmidt gap, and the inverse participation ratios can be used to detect the critical points of quantum phase transitions. Results drawn from these quantum information observables agree well with each other. Finally we provide a ground-state phase diagram as functions of the exchange anisotropy Δ and the rhombic single-ion anisotropy E .

Charge distribution in an two-chain dual model

International Nuclear Information System (INIS)

Fialkowski, K.; Kotanski, A.

1983-01-01

Charge distributions in the multiple production processes are analysed using the dual chain model. A parametrisation of charge distributions for single dual chains based on the νp and anti vp data is proposed. The rapidity charge distributions are then calculated for pp and anti pp collisions and compared with the previous calculations based on the recursive cascade model of single chains. The results differ at the SPS collider energies and in the energy dependence of the net forward charge supplying the useful tests of the dual chain model. (orig.)

Realities of Supply Chain Collaboration

NARCIS (Netherlands)

Kampstra, R.P.; Ashayeri, J.; Gattorna, J.

2006-01-01

Successful supply chain collaboration (SCC) practices are rather exceptional, yet collaboration is believed to be the single most pressing need in supply chain management.In this paper we discuss the realities of SCC, present prerequisites for the collaboration process, indicate where the process

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

Chain formation of metal atoms

DEFF Research Database (Denmark)

Bahn, Sune Rastad; Jacobsen, Karsten Wedel

2001-01-01

The possibility of formation of single-atomic chains by manipulation of nanocontacts is studied for a selection of metals (Ni, Pd, Pt, Cu, Ag, Au). Molecular dynamics simulations show that the tendency for chain formation is strongest for Au and Pt. Density functional theory calculations indicate...... that the metals which form chains exhibit pronounced many-atom interactions with strong bonding in low coordinated systems....

Efficient white organic light emission by single emitting layer

Energy Technology Data Exchange (ETDEWEB)

Ko, Young Wook; Chung, Choong-Heui; Lee, Jin Ho; Kim, Yong-Hae; Sohn, Choong-Yong; Kim, Bong-Chul; Hwang, Chi-Sun; Song, Yoon-Ho; Lim, Jongtae; Ahn, Young-Joo; Kang, Gi-Wook; Lee, Namheon; Lee, Changhee

2003-02-24

Stable organic white light-emitting diodes are successfully fabricated by a single organic white emitting layer, which is Bis (2-methyl-8-quinolinato) (triphenylsiloxy) aluminum (III) (SAlq) doped red fluorescent dye of 4-(dicyanomethylene)-2-tert-butyl-6(1,1,7,7-tetramethyljulolidyl-9-enyl)- 4H-pyran (DCJTB). The incomplete energy transfer from blue-emitting SAlq to red-emitting DCJTB enables to obtain a stable white balanced light-emission by the DCJTB doping concentration of 0.5%. A device with the structure of ITO/TPD (50 nm)/SAlq:DCJTB (30 nm, 0.5%)/Alq{sub 3} (20 nm)/LiF (0.5 nm)/Al (110 nm) shows maximum luminance of 20 400 cd/m{sup 2} at 810 mA/cm{sup 2}, external quantum efficiency of 2% at 200 cd/m{sup 2} ({approx}3 mA/cm{sup 2}), power efficiency of 2.3 lm/W at 67 cd/m{sup 2} ({approx}1 mA/cm{sup 2}), and a Commission Internationale de l'Eclairage chromaticity coordinates of (0.34, 0.39) at 1.8 mA/cm{sup 2} to (0.31, 0.38) at 36 mA/cm{sup 2}.

Phase transitions in single macromolecules: Loop-stretch transition versus loop adsorption transition in end-grafted polymer chains

Science.gov (United States)

Zhang, Shuangshuang; Qi, Shuanhu; Klushin, Leonid I.; Skvortsov, Alexander M.; Yan, Dadong; Schmid, Friederike

2018-01-01

We use Brownian dynamics simulations and analytical theory to compare two prominent types of single molecule transitions. One is the adsorption transition of a loop (a chain with two ends bound to an attractive substrate) driven by an attraction parameter ɛ and the other is the loop-stretch transition in a chain with one end attached to a repulsive substrate, driven by an external end-force F applied to the free end. Specifically, we compare the behavior of the respective order parameters of the transitions, i.e., the mean number of surface contacts in the case of the adsorption transition and the mean position of the chain end in the case of the loop-stretch transition. Close to the transition points, both the static behavior and the dynamic behavior of chains with different length N are very well described by a scaling ansatz with the scaling parameters (ɛ - ɛ*)Nϕ (adsorption transition) and (F - F*)Nν (loop-stretch transition), respectively, where ϕ is the crossover exponent of the adsorption transition and ν is the Flory exponent. We show that both the loop-stretch and the loop adsorption transitions provide an exceptional opportunity to construct explicit analytical expressions for the crossover functions which perfectly describe all simulation results on static properties in the finite-size scaling regime. Explicit crossover functions are based on the ansatz for the analytical form of the order parameter distributions at the respective transition points. In contrast to the close similarity in equilibrium static behavior, the dynamic relaxation at the two transitions shows qualitative differences, especially in the strongly ordered regimes. This is attributed to the fact that the surface contact dynamics in a strongly adsorbed chain is governed by local processes, whereas the end height relaxation of a strongly stretched chain involves the full spectrum of Rouse modes.

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.

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.

Quantum communication and state transfer in spin chains

International Nuclear Information System (INIS)

Van der Jeugt, Joris

2011-01-01

We investigate the time evolution of a single spin excitation state in certain linear spin chains, as a model for quantum communication. We consider first the simplest possible spin chain, where the spin chain data (the nearest neighbour interaction strengths and the magnetic field strengths) are constant throughout the chain. The time evolution of a single spin state is determined, and this time evolution is illustrated by means of an animation. Some years ago it was discovered that when the spin chain data are of a special form so-called perfect state transfer takes place. These special spin chain data can be linked to the Jacobi matrix entries of Krawtchouk polynomials or dual Hahn polynomials. We discuss here the case related to Krawtchouk polynomials, and illustrate the possibility of perfect state transfer by an animation showing the time evolution of the spin chain from an initial single spin state. Very recently, these ideas were extended to discrete orthogonal polynomials of q-hypergeometric type. Here, a remarkable result is a new analytic model where perfect state transfer is achieved: this is when the spin chain data are related to the Jacobi matrix of q-Krawtchouk polynomials. This case is discussed here, and again illustrated by means of an animation.

Exactly solved mixed spin-(1,1/2) Ising–Heisenberg diamond chain with a single-ion anisotropy

International Nuclear Information System (INIS)

Lisnyi, Bohdan; Strečka, Jozef

2015-01-01

The mixed spin-(1,1/2) Ising–Heisenberg diamond chain with a single-ion anisotropy is exactly solved through the generalized decoration–iteration transformation and the transfer-matrix method. The decoration–iteration transformation is first used for establishing a rigorous mapping equivalence with the corresponding spin-1 Blume–Emery–Griffiths chain, which is subsequently exactly treated within the transfer-matrix technique. Apart from three classical ground states the model exhibits three striking quantum ground states in which a singlet-dimer state of the interstitial Heisenberg spins is accompanied either with a frustrated state or a polarized state or a non-magnetic state of the nodal Ising spins. It is evidenced that two magnetization plateaus at zero and/or one-half of the saturation magnetization may appear in low-temperature magnetization curves. The specific heat may display remarkable temperature dependences with up to three and four distinct round maxima in a zero and non-zero magnetic field, respectively. - Highlights: • Mixed spin-(1,1/2) Ising–Heisenberg diamond chain is exactly solved. • Quantum ground states with a singlet-dimer state of the Heisenberg spins are found. • Magnetization curve displays intermediate plateaus at zero and half of full magnetization. • Thermal dependences of specific heat may display up to four distinct peaks

Ground state properties of a spin chain within Heisenberg model with a single lacking spin site

International Nuclear Information System (INIS)

Mebrouki, M.

2011-01-01

The ground state and first excited state energies of an antiferromagnetic spin-1/2 chain with and without a single lacking spin site are computed using exact diagonalization method, within the Heisenberg model. In order to keep both parts of a spin chain with a lacking site connected, next nearest neighbors interactions are then introduced. Also, the Density Matrix Renormalization Group (DMRG) method is used, to investigate ground state energies of large system sizes; which permits us to inquire about the effect of large system sizes on energies. Other quantum quantities such as fidelity and correlation functions are also studied and compared in both cases. - Research highlights: → In this paper we compute ground state and first excited state energies of a spin chain with and without a lacking spin site. The next nearest neighbors are introduced with the antiferromagnetic Heisenberg spin-half. → Exact diagonalization is used for small systems, where DMRG method is used to compute energies for large systems. Other quantities like quantum fidelity and correlation are also computed. → Results are presented in figures with comments. → E 0 /N is computed in a function of N for several values of J 2 and for both systems. First excited energies are also investigated.

Observation of a commensurate array of flux chains in tilted flux lattices in Bi-Sr-Ca-Cu-O single crystals

International Nuclear Information System (INIS)

Bolle, C.A.; Gammel, P.L.; Grier, D.G.; Murray, C.A.; Bishop, D.J.; Mitzi, D.B.; Kapitulnik, A.

1991-01-01

We report the observation of a novel flux-lattice structure, a commensurate array of flux-line chains. Our experiments consist of the magnetic decoration of the flux lattices in single crystals of Ba-Sr-Ca-Cu-O where the magnetic field is applied at an angle with respect to the conducting planes. For a narrow range of angles, the equilibrium structure is one with uniformly spaced chains with a higher line density of vortices than the background lattice. Our observations are in qualitative agreement with theories which suggest that, in strongly anisotropic materials the vortices develop an attractive interaction in tilted magnetic fields

Calculation of single chain cellulose elasticity using fully atomistic modeling

Science.gov (United States)

Xiawa Wu; Robert J. Moon; Ashlie Martini

2011-01-01

Cellulose nanocrystals, a potential base material for green nanocomposites, are ordered bundles of cellulose chains. The properties of these chains have been studied for many years using atomic-scale modeling. However, model predictions are difficult to interpret because of the significant dependence of predicted properties on model details. The goal of this study is...

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.

A uranium-based UO{sub 2}{sup +}-Mn{sup 2+} single-chain magnet assembled trough cation-cation interactions

Energy Technology Data Exchange (ETDEWEB)

Mougel, Victor; Chatelain, Lucile; Hermle, Johannes; Pecaut, Jacques; Mazzanti, Marinella [Laboratoire de Reconnaissance Ionique et Chimie de Coordination, SCIB, UMR-E3 CEA-UJF, INAC, CEA-Grenoble (France); Caciuffo, Roberto; Colineau, Eric [European Commission, Joint Research Centre, Institute for Transuranium Elements, Karlsruhe (Germany); Tuna, Floriana [EPSRC UK EPR Facility, School of Chemistry and Photon Science Institute, The University of Manchester (United Kingdom); Magnani, Nicola [Institute of Nanotechnology, Karlsruhe Institute of Technology, Eggenstein-Leopoldshafen (Germany); Geyer, Arnaud de [Service General des Rayons X, SP2M, INAC, CEA-Grenoble (France)

2014-01-13

Single-chain magnets (SCMs) are materials composed of magnetically isolated one-dimensional (1D) units exhibiting slow relaxation of magnetization. The occurrence of SCM behavior requires the fulfillment of stringent conditions for exchange and anisotropy interactions. Herein, we report the synthesis, the structure, and the magnetic characterization of the first actinide-containing SCM. The 5f-3d heterometallic 1D chains [{[UO_2(salen)(py)][M(py)_4](NO_3)}]{sub n}, (M=Cd (1) and M=Mn (2); py=pyridine) are assembled trough cation-cation interaction from the reaction of the uranyl(V) complex [UO{sub 2}(salen)py][Cp*{sub 2}Co] (Cp*=pentamethylcyclopentadienyl) with Cd(NO{sub 3}){sub 2} or Mn(NO{sub 3}){sub 2} in pyridine. The infinite UMn chain displays a high relaxation barrier of 134 ±0.8 K (93 ±0.5 cm{sup -1}), probably as a result of strong intra-chain magnetic interactions combined with the high Ising anisotropy of the uranyl(V) dioxo group. It also exhibits an open magnetic hysteresis loop at T <6 K, with an impressive coercive field of 3.4 T at 2 K. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

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

Single-molecule fluorescence microscopy review: shedding new light on old problems.

Science.gov (United States)

Shashkova, Sviatlana; Leake, Mark C

2017-08-31

Fluorescence microscopy is an invaluable tool in the biosciences, a genuine workhorse technique offering exceptional contrast in conjunction with high specificity of labelling with relatively minimal perturbation to biological samples compared with many competing biophysical techniques. Improvements in detector and dye technologies coupled to advances in image analysis methods have fuelled recent development towards single-molecule fluorescence microscopy, which can utilize light microscopy tools to enable the faithful detection and analysis of single fluorescent molecules used as reporter tags in biological samples. For example, the discovery of GFP, initiating the so-called 'green revolution', has pushed experimental tools in the biosciences to a completely new level of functional imaging of living samples, culminating in single fluorescent protein molecule detection. Today, fluorescence microscopy is an indispensable tool in single-molecule investigations, providing a high signal-to-noise ratio for visualization while still retaining the key features in the physiological context of native biological systems. In this review, we discuss some of the recent discoveries in the life sciences which have been enabled using single-molecule fluorescence microscopy, paying particular attention to the so-called 'super-resolution' fluorescence microscopy techniques in live cells, which are at the cutting-edge of these methods. In particular, how these tools can reveal new insights into long-standing puzzles in biology: old problems, which have been impossible to tackle using other more traditional tools until the emergence of new single-molecule fluorescence microscopy techniques. © 2017 The Author(s).

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.

Self-assembly surface modified indium-tin oxide anodes for single-layer light-emitting diodes

CERN Document Server

Morgado, J; Charas, A; Matos, M; Alcacer, L; Cacialli, F

2003-01-01

We study the effect of indium-tin oxide surface modification by self assembling of highly polar molecules on the performance of single-layer light-emitting diodes (LEDs) fabricated with polyfluorene blends and aluminium cathodes. We find that the efficiency and light-output of such LEDs is comparable to, and sometimes better than, the values obtained for LEDs incorporating a hole injection layer of poly(3,4-ethylene dioxythiophene) doped with polystyrene sulphonic acid. This effect is attributed to the dipole-induced work function modification of indium-tin oxide.

Self-assembly surface modified indium-tin oxide anodes for single-layer light-emitting diodes

International Nuclear Information System (INIS)

Morgado, Jorge; Barbagallo, Nunzio; Charas, Ana; Matos, Manuel; Alcacer, Luis; Cacialli, Franco

2003-01-01

We study the effect of indium-tin oxide surface modification by self assembling of highly polar molecules on the performance of single-layer light-emitting diodes (LEDs) fabricated with polyfluorene blends and aluminium cathodes. We find that the efficiency and light-output of such LEDs is comparable to, and sometimes better than, the values obtained for LEDs incorporating a hole injection layer of poly(3,4-ethylene dioxythiophene) doped with polystyrene sulphonic acid. This effect is attributed to the dipole-induced work function modification of indium-tin oxide

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.

Cylindrical polymer brushes with dendritic side chains by iterative anionic reactions

KAUST Repository

Zhang, Hefeng

2015-05-01

We report in this paper an easy method for the synthesis of cylindrical polymer brushes with dendritic side chains through anionic reaction. The synthesis is accomplished by iteratively grafting a living block copolymer, polyisoprene-. b-polystyrenyllithium (PI-. b-PSLi), to the main chain and subsequently to the branches in a divergent way. PI segment is short and serves as a precursor for multifunctional branching unit. The grafting reaction involves two successive steps: i) epoxidation of internal double bonds of PI segments, either in main chain or side chains; ii) ring-opening addition to the resulting epoxy group by the living PI-. b-PSLi. Repeating the two steps affords a series of cylindrical polymer brushes with up to 3rd generation and extremely high molecular weight. The branching multiplicity depends on the average number of oxirane groups per PI segment, usually ca. 8 in the present work. The high branching multiplicity leads to tremendous increase in molecular weights of the cylindrical products with generation growth. Several series of cylindrical polymer brushes with tunable aspect ratios are prepared using backbones and branches with controlled lengths. Shape anisotropy is investigated in dilute solution using light scattering technique. Worm-like single molecular morphology with large persistence length is observed on different substrates by atomic force microscopy.

Manipulating Ion Migration for Highly Stable Light-Emitting Diodes with Single-Crystalline Organometal Halide Perovskite Microplatelets.

Science.gov (United States)

Chen, Mingming; Shan, Xin; Geske, Thomas; Li, Junqiang; Yu, Zhibin

2017-06-27

Ion migration has been commonly observed as a detrimental phenomenon in organometal halide perovskite semiconductors, causing the measurement hysteresis in solar cells and ultrashort operation lifetimes in light-emitting diodes. In this work, ion migration is utilized for the formation of a p-i-n junction at ambient temperature in single-crystalline organometal halide perovskites. The junction is subsequently stabilized by quenching the ionic movement at a low temperature. Such a strategy of manipulating the ion migration has led to efficient single-crystalline light-emitting diodes that emit 2.3 eV photons starting at 1.8 V and sustain a continuous operation for 54 h at ∼5000 cd m -2 without degradation of brightness. In addition, a whispering-gallery-mode cavity and exciton-exciton interaction in the perovskite microplatelets have both been observed that can be potentially useful for achieving electrically driven laser diodes based on single-crystalline organometal halide perovskite semiconductors.

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

Heterogeneous Single-Atom Catalyst for Visible-Light-Driven High-Turnover CO2 Reduction: The Role of Electron Transfer.

Science.gov (United States)

Gao, Chao; Chen, Shuangming; Wang, Ying; Wang, Jiawen; Zheng, Xusheng; Zhu, Junfa; Song, Li; Zhang, Wenkai; Xiong, Yujie

2018-03-01

Visible-light-driven conversion of CO 2 into chemical fuels is an intriguing approach to address the energy and environmental challenges. In principle, light harvesting and catalytic reactions can be both optimized by combining the merits of homogeneous and heterogeneous photocatalysts; however, the efficiency of charge transfer between light absorbers and catalytic sites is often too low to limit the overall photocatalytic performance. In this communication, it is reported that the single-atom Co sites coordinated on the partially oxidized graphene nanosheets can serve as a highly active and durable heterogeneous catalyst for CO 2 conversion, wherein the graphene bridges homogeneous light absorbers with single-atom catalytic sites for the efficient transfer of photoexcited electrons. As a result, the turnover number for CO production reaches a high value of 678 with an unprecedented turnover frequency of 3.77 min -1 , superior to those obtained with the state-of-the-art heterogeneous photocatalysts. This work provides fresh insights into the design of catalytic sites toward photocatalytic CO 2 conversion from the angle of single-atom catalysis and highlights the role of charge kinetics in bridging the gap between heterogeneous and homogeneous photocatalysts. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cell surface expression of single chain antibodies with applications to imaging of gene expression in vivo

International Nuclear Information System (INIS)

Northrop, Jeffrey P.; Bednarski, Mark; Li, King C.; Barbieri, Susan O.; Lu, Amy T.; Nguyen, Dee; Varadarajan, John; Osen, Maureen; Star-Lack, Josh

2003-01-01

Imaging of gene expression in vivo has many potential uses for biomedical research and drug discovery, ranging from the study of gene regulation and cancer to the non-invasive assessment of gene therapies. To streamline the development of imaging marker gene technologies for nuclear medicine, we propose a new approach to the design of reporter/probe pairs wherein the reporter is a cell surface-expressed single chain antibody variable fragment that has been raised against a low molecular weight imaging probe with optimized pharmacokinetic properties. Proof of concept of the approach was achieved using a single chain antibody variable fragment that binds with high affinity to fluorescein and an imaging probe consisting of fluorescein isothiocyanate coupled to the chelator diethylene triamine penta-acetic acid labeled with the gamma-emitter 111 In. We demonstrate specific high-affinity binding of this probe to the cell surface-expressed reporter in vitro and assess the in vivo biodistribution of the probe both in wild-type mice and in mice harboring tumor xenografts expressing the reporter. Specific uptake of the probe by, and in vivo imaging of, tumors expressing the reporter are shown. Since ScFvs with high affinities can be raised to almost any protein or small molecule, the proposed methodology may offer a new flexibility in the design of imaging tracer/reporter pairs wherein both probe pharmacokinetics and binding affinities can be readily optimized. (orig.)

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.

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.

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

A 3 W High-Voltage Single-Chip Green Light-Emitting Diode with Multiple-Cells Network

Directory of Open Access Journals (Sweden)

W. Wang

2015-01-01

Full Text Available A parallel and series network structure was introduced into the design of the high-voltage single-chip (HV-SC light-emitting diode to inhibit the effect of current crowding and to improve the yield. Using such a design, a 6.6×5 mm2 large area LED chip of 24 parallel stages was demonstrated with 3 W light output power (LOP at the current of 500 mA. The forward voltage was measured to be 83 V with the same current injection, corresponding to 3.5 V for a single stage. The LED chip’s average thermal resistance was identified to be 0.28 K/W by using infrared thermography analysis.

Light-dependent electrogenic activity of cyanobacteria.

Directory of Open Access Journals (Sweden)

John M Pisciotta

2010-05-01

Full Text Available Cyanobacteria account for 20-30% of Earth's primary photosynthetic productivity and convert solar energy into biomass-stored chemical energy at the rate of approximately 450 TW [1]. These single-cell microorganisms are resilient predecessors of all higher oxygenic phototrophs and can be found in self-sustaining, nitrogen-fixing communities the world over, from Antarctic glaciers to the Sahara desert [2].Here we show that diverse genera of cyanobacteria including biofilm-forming and pelagic strains have a conserved light-dependent electrogenic activity, i.e. the ability to transfer electrons to their surroundings in response to illumination. Naturally-growing biofilm-forming photosynthetic consortia also displayed light-dependent electrogenic activity, demonstrating that this phenomenon is not limited to individual cultures. Treatment with site-specific inhibitors revealed the electrons originate at the photosynthetic electron transfer chain (P-ETC. Moreover, electrogenic activity was observed upon illumination only with blue or red but not green light confirming that P-ETC is the source of electrons. The yield of electrons harvested by extracellular electron acceptor to photons available for photosynthesis ranged from 0.05% to 0.3%, although the efficiency of electron harvesting likely varies depending on terminal electron acceptor.The current study illustrates that cyanobacterial electrogenic activity is an important microbiological conduit of solar energy into the biosphere. The mechanism responsible for electrogenic activity in cyanobacteria appears to be fundamentally different from the one exploited in previously discovered electrogenic bacteria, such as Geobacter, where electrons are derived from oxidation of organic compounds and transported via a respiratory electron transfer chain (R-ETC [3], [4]. The electrogenic pathway of cyanobacteria might be exploited to develop light-sensitive devices or future technologies that convert solar

Generation of three wide frequency bands within a single white-light cavity

Science.gov (United States)

Othman, Anas; Yevick, David; Al-Amri, M.

2018-04-01

We theoretically investigate the double-Λ scheme inside a Fabry-Pérot cavity employing a weak probe beam and two strong driving fields together with an incoherent pumping mechanism. By generating analytical expressions for the susceptibility and applying the white-light cavity conditions, we devise a procedure that reaches the white-light condition at a smaller gas density than the values typically cited in similar previous studies. Further, when the intensities of the two driving fields are equal, a single giant white band is obtained, while for unequal driving fields three white bands can be present in the cavity. Two additional techniques are then advanced for generating three white bands and a method is described for displacing the center frequency of the bands. Finally, some potential applications are suggested.

Direct photoaffinity labeling by nucleotides of the apparent catalytic site on the heavy chains of smooth muscle and Acanthamoeba myosins

International Nuclear Information System (INIS)

Maruta, H.; Korn, E.D.

1981-01-01

The heavy chains of Acanthamoeba myosins, IA, IB and II, turkey gizzard myosin, and rabbit skeletal muscle myosin subfragment-1 were specifically labeled by radioactive ATP, ADP, and UTP, each of which is a substrate or product of myosin ATPase activity, when irradiated with uv light at 0 0 C. With UTP, as much as 0.45 mol/mol of Acanthamoeba myosin IA heavy chain and 1 mol/mol of turkey gizzard myosin heavy chain was incorporated. Evidence that the ligands were associated with the catalytic site included the observations that reaction occurred only with nucleotides that are substrates or products of the ATPase activity; that the reaction was blocked by pyrophosphate which is an inhibitor of the ATPase activity; that ATP was bound as ADP; and that label was probably restricted to a single peptide following limited subtilisin proteolysis of labeled Acanthamoeba myosin IA heavy chain and extensive cleavage with CNBr and trypsin of labeled turkey gizzard myosin heavy chain

Luminescence- and nanoparticle-mediated increase of light absorption by photoreceptor cells: Converting UV light to visible light

OpenAIRE

Li, Lei; Sahi, Sunil K.; Peng, Mingying; Lee, Eric B.; Ma, Lun; Wojtowicz, Jennifer L.; Malin, John H.; Chen, Wei

2016-01-01

We developed new optic devices ? singly-doped luminescence glasses and nanoparticle-coated lenses that convert UV light to visible light ? for improvement of visual system functions. Tb3+ or Eu3+ singly-doped borate glasses or CdS-quantum dot (CdS-QD) coated lenses efficiently convert UV light to 542?nm or 613?nm wavelength narrow-band green or red light, or wide-spectrum white light, and thereby provide extra visible light to the eye. In zebrafish (wild-type larvae and adult control animals,...

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

Single-chain magnet features in 1D [MnR{sub 4}TPP][TCNE] compounds

Energy Technology Data Exchange (ETDEWEB)

Balanda, Maria [Institute of Nuclear Physics PAN, Radzikowskiego 152, 31-342 Krakow (Poland); Tomkowicz, Zbigniew; Rams, Michal [Institute of Physics, Jagiellonian University, Reymonta 4, 30-059 Krakow (Poland); Haase, Wolfgang, E-mail: Maria.Balanda@ifj.edu.pl [Institute of Physical Chemistry, Darmstadt University of Technology, 64287 Darmstadt (Germany)

2011-07-06

Molecular chains of antiferrimagnetically coupled Mn{sup III}-ion (S = 2) and TCNE (tetracyanoethylene) radical moments (s = 1/2 ) show different behaviour depending on group R substituted to TPP (tetraphenylporphyrin) and on the substitution site. The compound with R = F in Ortho position is a Single-Chain Magnet (SCM) with blocking temperature T{sub b} = 6.6K, while that with R = F in Meta position shows both blocking (T{sub b} = 5.4 K) and magnetic ordering transition (T{sub c} = 10 K). For bulky groups R = OC{sub n}H{sub 2n+1}, the magnetically ordered phase is observed (T{sub c} {approx} 22 K), which does not however prevent slow relaxation at T <8 K. Magnetic hysteresis with coercive field H{sub c} of 2 T at 2.3 K is like that of SCM. The frequency dependent AC susceptibility in the superimposed DC field reveals common features of all systems. The energy of intrachain ferromagnetic coupling between effective spin units 3/2, relevant at low temperatures, is determined for all compounds and the interchain dipolar coupling is estimated. It is concluded that slow relaxation is inherent for all quasi one-dimensional compounds and for the magnetically ordered ones shows up in the high enough magnetic field.

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)

Efficient polymer white-light-emitting diodes with a single-emission layer of fluorescent polymer blend

International Nuclear Information System (INIS)

Niu Qiaoli; Xu Yunhua; Jiang Jiaxing; Peng Junbiao; Cao Yong

2007-01-01

Efficient polymer white-light-emitting diodes (WPLEDs) have been fabricated with a single layer of fluorescent polymer blend. The device structure consists of ITO/PEDOT/PVK/emissive layer/Ba/Al. The emissive layer is a blend of poly(9,9-dioctylfluorene) (PFO), phenyl-substituted PPV derivative (P-PPV) and a copolymer of 9,9-dioctylfluorene and 4,7-di(4-hexylthien-2-yl)-2,1,3-benzothiadiazole (PFO-DHTBT), which, respectively, emits blue, green and red light. The emission of pure and efficient white light was implemented by tuning the blend weight ratio of PFO: P-PPV: PFO-DHTBT to 96:4:0.4. The maximum current efficiency and luminance are, respectively, 7.6 cd/A at 6.7 V and 11930 cd/m 2 at 11.2 V. The CIE coordinates of white-light emission were stable with the drive voltages

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.

Analysis of the relationship between end-to-end distance and activity of single-chain antibody against colorectal carcinoma.

Science.gov (United States)

Zhang, Jianhua; Liu, Shanhong; Shang, Zhigang; Shi, Li; Yun, Jun

2012-08-22

We investigated the relationship of End-to-end distance between VH and VL with different peptide linkers and the activity of single-chain antibodies by computer-aided simulation. First, we developed (G4S)n (where n = 1-9) as the linker to connect VH and VL, and estimated the 3D structure of single-chain Fv antibody (scFv) by homologous modeling. After molecular models were evaluated and optimized, the coordinate system of every protein was built and unified into one coordinate system, and End-to-end distances calculated using 3D space coordinates. After expression and purification of scFv-n with (G4S)n as n = 1, 3, 5, 7 or 9, the immunoreactivity of purified ND-1 scFv-n was determined by ELISA. A multi-factorial relationship model was employed to analyze the structural factors affecting scFv: rn=ABn-ABO2+CDn-CDO2+BCn-BCst2. The relationship between immunoreactivity and r-values revealed that fusion protein structure approached the desired state when the r-value = 3. The immunoreactivity declined as the r-value increased, but when the r-value exceeded a certain threshold, it stabilized. We used a linear relationship to analyze structural factors affecting scFv immunoreactivity.

Consistency of the single calculus chain for climatological studies using long-term measurements from thessaloniki lidar station

Science.gov (United States)

Siomos, Nikolaos; Voudouri, Kalliopi A.; Filioglou, Maria; Giannakaki, Eleni; Amiridis, Vasilis; D'Amico, Giuseppe; Balis, Dimitris S.

2018-04-01

The long term analysis of 15 years of lidar data derived from a Raman lidar at Thessaloniki is presented here. All measurements have been processed with the latest version 4 of the EARLINET Single Calculus Chain algorithm and are compared with the results from the current operational retrieval algorithm. In this paper we investigate the consistency between the EARLINET database and SCC for the case of Thessaloniki and we identify the issues to be considered when switching from current operations to SCC.

Fluorescence polarization measures energy funneling in single light-harvesting antennas--LH2 vs conjugated polymers.

Science.gov (United States)

Camacho, Rafael; Tubasum, Sumera; Southall, June; Cogdell, Richard J; Sforazzini, Giuseppe; Anderson, Harry L; Pullerits, Tõnu; Scheblykin, Ivan G

2015-10-19

Numerous approaches have been proposed to mimic natural photosynthesis using artificial antenna systems, such as conjugated polymers (CPs), dendrimers, and J-aggregates. As a result, there is a need to characterize and compare the excitation energy transfer (EET) properties of various natural and artificial antennas. Here we experimentally show that EET in single antennas can be characterized by 2D polarization imaging using the single funnel approximation. This methodology addresses the ability of an individual antenna to transfer its absorbed energy towards a single pool of emissive states, using a single parameter called energy funneling efficiency (ε). We studied individual peripheral antennas of purple bacteria (LH2) and single CP chains of 20 nm length. As expected from a perfect antenna, LH2s showed funneling efficiencies close to unity. In contrast, CPs showed lower average funneling efficiencies, greatly varying from molecule to molecule. Cyclodextrin insulation of the conjugated backbone improves EET, increasing the fraction of CPs possessing ε = 1. Comparison between LH2s and CPs shows the importance of the protection systems and the protein scaffold of LH2, which keep the chromophores in functional form and at such geometrical arrangement that ensures excellent EET.

Formation and properties of metal-oxygen atomic chains

DEFF Research Database (Denmark)

Thijssen, W.H.A.; Strange, Mikkel; de Brugh, J.M.J.A.

2008-01-01

of longer atomic chains. The mechanical and electrical properties of these diatomic chains have been investigated by determining local vibration modes of the chain and by measuring the dependence of the average chain-conductance on the length of the chain. Additionally, we have performed calculations......Suspended chains consisting of single noble metal and oxygen atoms have been formed. We provide evidence that oxygen can react with and be incorporated into metallic one-dimensional atomic chains. Oxygen incorporation reinforces the linear bonds in the chain, which facilitates the creation...

Graphene metamaterial spatial light modulator for infrared single pixel imaging.

Science.gov (United States)

Fan, Kebin; Suen, Jonathan Y; Padilla, Willie J

2017-10-16

High-resolution and hyperspectral imaging has long been a goal for multi-dimensional data fusion sensing applications - of interest for autonomous vehicles and environmental monitoring. In the long wave infrared regime this quest has been impeded by size, weight, power, and cost issues, especially as focal-plane array detector sizes increase. Here we propose and experimentally demonstrated a new approach based on a metamaterial graphene spatial light modulator (GSLM) for infrared single pixel imaging. A frequency-division multiplexing (FDM) imaging technique is designed and implemented, and relies entirely on the electronic reconfigurability of the GSLM. We compare our approach to the more common raster-scan method and directly show FDM image frame rates can be 64 times faster with no degradation of image quality. Our device and related imaging architecture are not restricted to the infrared regime, and may be scaled to other bands of the electromagnetic spectrum. The study presented here opens a new approach for fast and efficient single pixel imaging utilizing graphene metamaterials with novel acquisition strategies.

Single-phased CaAl2Si2O8:Tm3+, Dy3+ white-light phosphors under ultraviolet excitation

International Nuclear Information System (INIS)

Yang, Penghui; Yu, Xue; Xu, Xuhui; Jiang, Tingming; Yu, Hongling; Zhou, Dacheng; Yang, Zhengwen; Song, Zhiguo; Qiu, Jianbei

2013-01-01

A novel white-light-emitting phosphor CaAl 2 Si 2 O 8 :Tm, Dy was synthesized in ambient atmosphere by solid-state reaction. The energy transfer from Tm 3+ to Dy 3+ ions via a dipole–quadrupole reaction was observed and investigated. Upon UV excitation, white light emission was achieved by integrating a blue emission band located at 455 nm and an orange one located at 574 nm attributed to Tm 3+ and Dy 3+ ions, respectively. In addition, the energy-transfer efficiency and critical distance were calculated. Results suggested that the phosphor might be promising as a single-phased white-light-emitting phosphor for UV white-light LED. - Graphical abstract: The results indicate the existence of energy transfer from Tm 3+ to Dy 3+ . By tuning the concentration of Dy 3+ , single-phased white light can be realized. - Highlights: ► Energy transfer from Tm 3+ to Dy 3+ was investigated. ► Color tunable from blue to white can be achieved. ► White light can be realized in CaAl 2 Si 2 O 8 :Tm 3+ , Dy 3+ phosphor

Single-phased white-light-emitting Sr3NaLa(PO4)3F: Eu2+,Mn2+ phosphor via energy transfer

International Nuclear Information System (INIS)

Shanshan, Hu; Wanjun, Tang

2014-01-01

Single-phased white-light-emitting Sr 3 NaLa(PO 4 ) 3 F:Eu 2+ ,Mn 2+ phosphor is synthesized via the combustion-assisted synthesis technique. Upon excitation of 344 nm ultraviolet (UV) light, two intense broad bands have clearly been obtained due to the allowed 5d–4f transition of Eu 2+ and the forbidden 4 T 1 − 6 A 1 transition of Mn 2+ , respectively. As a result of fine-tuning of the emission composition of the Eu 2+ and Mn 2+ ions, white-light emission can be realized by combining the emission of Eu 2+ and Mn 2+ in a single host lattice under UV light excitation. The obtained phosphor exhibits a strong excitation band between 250 and 420 nm, matching well with the dominant emission band of a UV light-emitting-diode (LED) chip, which could be a promising candidate for UV-converting white-light-emitting diodes (LEDs). -- Highlights: • Single-phased Sr 3 NaLa(PO 4 ) 3 F:Eu 2+ ,Mn 2+ phosphors are synthesized. • Sr 3 NaLa(PO 4 ) 3 F:Eu 2+ ,Mn 2+ shows a blue emission band and a yellow emission band. • White-emitting can be obtained by tuning the compositions of the Eu 2+ and Mn 2+

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.

A family of rare-earth-based single chain magnets: playing with anisotropy.

Science.gov (United States)

Bernot, Kevin; Bogani, Lapo; Caneschi, Andrea; Gatteschi, Dante; Sessoli, Roberta

2006-06-21

The first family of rare-earth-based single chain magnets is presented. Compounds of general formula [M(hfac)3(NITPhOPh)], where M = Eu, Gd, Tb, Dy, Ho, Er, or Yb, and PhOPh is the nitronyl-nitroxide radical (2,4'-benzoxo-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide), have been structurally characterized and found to be isostructural. The characterization of both static and dynamic magnetic properties of the whole family is reported. Dy, Tb, and Ho compounds display slow relaxation of the magnetization, and ac susceptibility shows a thermally activated regime with energy barriers of 69, 45, and 34 K for Dy, Tb, and Ho compounds, respectively, while only a frequency-dependent susceptibility is observed for Er below 2.0 K. In Gd and Yb derivatives, antiferromagnetic interactions dominate. The pre-exponential factors differ by about 4 orders of magnitude. Finite size effects, due to naturally occurring defects, affect the static and dynamic properties of the compounds differently.

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

Design of Slow and Fast Light Photonic Crystal Waveguides for Single-photon Emission Using a Bloch Mode Expansion Technique

DEFF Research Database (Denmark)

de Lasson, Jakob Rosenkrantz; Rigal, B.; Kapon, E.

We design slow and fast light photonic crystal waveguides for single-photon emission using a Bloch mode expansion and scattering matrix technique. We propose slow light designs that increase the group index-waveguide mode volume ratio for larger Purcell enhancement, and address efficient slow-to-...

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.

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...

Comparison of reverse transcription-quantitative polymerase chain reaction methods and platforms for single cell gene expression analysis.

Science.gov (United States)

Fox, Bridget C; Devonshire, Alison S; Baradez, Marc-Olivier; Marshall, Damian; Foy, Carole A

2012-08-15

Single cell gene expression analysis can provide insights into development and disease progression by profiling individual cellular responses as opposed to reporting the global average of a population. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is the "gold standard" for the quantification of gene expression levels; however, the technical performance of kits and platforms aimed at single cell analysis has not been fully defined in terms of sensitivity and assay comparability. We compared three kits using purification columns (PicoPure) or direct lysis (CellsDirect and Cells-to-CT) combined with a one- or two-step RT-qPCR approach using dilutions of cells and RNA standards to the single cell level. Single cell-level messenger RNA (mRNA) analysis was possible using all three methods, although the precision, linearity, and effect of lysis buffer and cell background differed depending on the approach used. The impact of using a microfluidic qPCR platform versus a standard instrument was investigated for potential variability introduced by preamplification of template or scaling down of the qPCR to nanoliter volumes using laser-dissected single cell samples. The two approaches were found to be comparable. These studies show that accurate gene expression analysis is achievable at the single cell level and highlight the importance of well-validated experimental procedures for low-level mRNA analysis. Copyright © 2012 Elsevier Inc. All rights reserved.

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.

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…

Supply Chain Management in Albania: An Empirical Study

OpenAIRE

Alma Spaho, Thoma Mitre

2012-01-01

Supply chain management in Albania has received little attention in the recent literature. Many companies now realize that actions taken by one member of the chain can influence the profitability of all others in the chain. Companies are increasingly thinking in terms of competing as part of a supply chain against other supply chains, rather than as a single firm against other individual firms. The aim of the paper is to investigate the current situation of supply chain management in Albania ...

Quantum gates controlled by spin chain soliton excitations

Energy Technology Data Exchange (ETDEWEB)

Cuccoli, Alessandro, E-mail: cuccoli@fi.infn.it [Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy); Nuzzi, Davide [Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Vaia, Ruggero [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy); Verrucchi, Paola [Istituto dei Sistemi Complessi, Consiglio Nazionale delle Ricerche, I-50019 Sesto Fiorentino (Italy); Dipartimento di Fisica e Astronomia, Università di Firenze, I-50019 Sesto Fiorentino (Italy); Istituto Nazionale di Fisica Nucleare, Sezione di Firenze, I-50019 Sesto Fiorentino (Italy)

2014-05-07

Propagation of soliton-like excitations along spin chains has been proposed as a possible way for transmitting both classical and quantum information between two distant parties with negligible dispersion and dissipation. In this work, a somewhat different use of solitons is considered. Solitons propagating along a spin chain realize an effective magnetic field, well localized in space and time, which can be exploited as a means to manipulate the state of an external spin (i.e., a qubit) that is weakly coupled to the chain. We have investigated different couplings between the qubit and the chain, as well as different soliton shapes, according to a Heisenberg chain model. It is found that symmetry properties strongly affect the effectiveness of the proposed scheme, and the most suitable setups for implementing single qubit quantum gates are singled out.

Oxygen vacancy chain and conductive filament formation in hafnia

Science.gov (United States)

Xue, Kan-Hao; Miao, Xiang-Shui

2018-04-01

The stability and aggregation mechanisms of oxygen vacancy chains are studied for hafnia using self-energy corrected density functional theory. While oxygen vacancies tend not to align along the c-axis of monoclinic HfO2, oxygen vacancy chains along a-axis and b-axis are energetically favorable, with cohesive energies of 0.05 eV and 0.03 eV per vacancy, respectively. Nevertheless, with an increase of the cross section area, intensive oxygen vacancy chains become much more stable in hafnia, which yields phase separation into Hf-clusters and HfO2. Compared with disperse single vacancy chains, intensive oxygen vacancy chains made of 4, 6, and 8 single vacancy chains are energetically more favorable by 0.17, 0.20, and 0.30 eV per oxygen vacancy, respectively. On the other hand, while a single oxygen vacancy chain exhibits a tiny electronic energy gap of around 0.5 eV, metallic conduction emerges for the intensive vacancy chain made of 8 single vacancy chains, which possesses a filament cross section area of ˜0.4 nm2. This sets a lower area limit for Hf-cluster filaments from metallic conduction point of view, but in real hafnia resistive RAM devices the cross section area of the filaments can generally be much larger (>5 nm2) for the sake of energy minimization. Our work sets up a bridge between oxygen vacancy ordering and phase separation in hafnia, and shows a clear trend of filament stabilization with larger dimensions. The results could explain the threshold switching phenomenon in hafnia when a small AFM tip was used as the top electrode, as well as the undesired multimode operation in resistive RAM cells with 3 nm-thick hafnia.

Electrical and optical 3D modelling of light-trapping single-photon avalanche diode

Science.gov (United States)

Zheng, Tianzhe; Zang, Kai; Morea, Matthew; Xue, Muyu; Lu, Ching-Ying; Jiang, Xiao; Zhang, Qiang; Kamins, Theodore I.; Harris, James S.

2018-02-01

Single-photon avalanche diodes (SPADs) have been widely used to push the frontier of scientific research (e.g., quantum science and single-molecule fluorescence) and practical applications (e.g., Lidar). However, there is a typical compromise between photon detection efficiency and jitter distribution. The light-trapping SPAD has been proposed to break this trade-off by coupling the vertically incoming photons into a laterally propagating mode while maintaining a small jitter and a thin Si device layer. In this work, we provide a 3D-based optical and electrical model based on practical fabrication conditions and discuss about design parameters, which include surface texturing, photon injection position, device area, and other features.

Significantly enhanced visible light response in single TiO2 nanowire by nitrogen ion implantation

Science.gov (United States)

Wu, Pengcheng; Song, Xianyin; Si, Shuyao; Ke, Zunjian; Cheng, Li; Li, Wenqing; Xiao, Xiangheng; Jiang, Changzhong

2018-05-01

The metal-oxide semiconductor TiO2 shows enormous potential in the field of photoelectric detection; however, UV-light absorption only restricts its widespread application. It is considered that nitrogen doping can improve the visible light absorption of TiO2, but the effect of traditional chemical doping is far from being used for visible light detection. Herein, we dramatically broadened the absorption spectrum of the TiO2 nanowire (NW) by nitrogen ion implantation and apply the N-doped single TiO2 NW to visible light detection for the first time. Moreover, this novel strategy effectively modifies the surface states and thus regulates the height of Schottky barriers at the metal/semiconductor interface, which is crucial to realizing high responsivity and a fast response rate. Under the illumination of a laser with a wavelength of 457 nm, our fabricated photodetector exhibits favorable responsivity (8 A W-1) and a short response time (0.5 s). These results indicate that ion implantation is a promising method in exploring the visible light detection of TiO2.

Plasmonic Circuit Theory for Multiresonant Light Funneling to a Single Spatial Hot Spot.

Science.gov (United States)

Hughes, Tyler W; Fan, Shanhui

2016-09-14

We present a theoretical framework, based on plasmonic circuit models, for generating a multiresonant field intensity enhancement spectrum at a single "hot spot" in a plasmonic device. We introduce a circuit model, consisting of an array of coupled LC resonators, that directs current asymmetrically in the array, and we show that this circuit can funnel energy efficiently from each resonance to a single element. We implement the circuit model in a plasmonic nanostructure consisting of a series of metal bars of differing length, with nearest neighbor metal bars strongly coupled electromagnetically through air gaps. The resulting nanostructure resonantly traps different wavelengths of incident light in separate gap regions, yet it funnels the energy of different resonances to a common location, which is consistent with our circuit model. Our work is important for a number of applications of plasmonic nanoantennas in spectroscopy, such as in single-molecule fluorescence spectroscopy or Raman spectroscopy.

White light emitting device based on single-phase CdS quantum dots

Science.gov (United States)

Li, Feng; Nie, Chao; You, Lai; Jin, Xiao; Zhang, Qin; Qin, Yuancheng; Zhao, Feng; Song, Yinglin; Chen, Zhongping; Li, Qinghua

2018-05-01

White light emitting diodes (WLEDs) based on quantum dots (QDs) are emerging as robust candidates for white light sources, however they are suffering from the problem of energy loss resulting from the re-absorption and self-absorption among the employed QDs of different peak wavelengths. It still remains a challenging task to construct WLEDs based on single-phase QD emitters. Here, CdS QDs with short synthesis times are introduced to the fabrication of WLEDs. With a short synthesis time, on one hand, CdS QDs with a small diameter with blue emission can be obtained. On the other hand, surface reconstruction barely has time to occur, and the surface is likely defect-ridden, which enables the existence of a broad emission covering the range of green, yellow and red regions. This is essential for the white light emission of CdS QDs, and is very important for WLED applications. The temporal evolution of the PL spectra for CdS QDs was obtained to investigate the influence of growth time on the luminescent properties. The CdS QDs with a growth time of 0.5 min exhibited a colour rendering index (CRI) of 79.5 and a correlated colour temperature (CCT) of 6238 K. With increasing reaction time, the colour coordinates of the CdS QDs will move away from the white light region in the CIE 1931 chromaticity diagram. By integrating the as prepared white light emission CdS QDs with a violet GaN chip, WLEDs were fabricated. The fabricated WLEDs exhibited a CRI of 87.9 and a CCT of 4619 K, which satisfy the demand of general illumination. The luminous flux and the luminous efficiency of the fabricated WLEDs, being less advanced than current commercial white light sources, can be further improved, meaning there is a need for much more in-depth studies on white light emission CdS QDs.

White polymer light-emitting diodes based on star-shaped polymers with an orange dendritic phosphorescent core.

Science.gov (United States)

Zhu, Minrong; Li, Yanhu; Cao, Xiaosong; Jiang, Bei; Wu, Hongbin; Qin, Jingui; Cao, Yong; Yang, Chuluo

2014-12-01

A series of new star-shaped polymers with a triphenylamine-based iridium(III) dendritic complex as the orange-emitting core and poly(9,9-dihexylfluorene) (PFH) chains as the blue-emitting arms is developed towards white polymer light-emitting diodes (WPLEDs). By fine-tuning the content of the orange phosphor, partial energy transfer and charge trapping from the blue backbone to the orange core is realized to achieve white light emission. Single-layer WPLEDs with the configuration of ITO (indium-tin oxide)/poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS)/polymer/CsF/Al exhibit a maximum current efficiency of 1.69 cd A(-1) and CIE coordinates of (0.35, 0.33), which is very close to the pure white-light point of (0.33, 0.33). To the best of our knowledge, this is the first report on star-shaped white-emitting single polymers that simultaneously consist of fluorescent and phosphorescent species. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Stimulated polarization wave process in spin 3/2 chains

International Nuclear Information System (INIS)

Furman, G. B.

2007-01-01

Stimulated wave of polarization, triggered by a flip of a single spin, presents a simple model of quantum amplification. Recently, it has been demonstrated that, in an idealized one-dimensional Ising spin 1/2 chain with nearest-neighbor interactions and realistic spin 1/2 chain including the natural dipole-dipole interactions, irradiated by a weak resonant transverse field, a wave of flipped spins can be triggered by a single spin flip. Here we focuse on control of polarization wave in chain of spin 3/2, where the nuclear quadrupole interaction is dominant. Results of simulations for 1D spin chains and rings with up to five spins are presented.

Direct observation of the discrete energy spectrum of two lanthanide-based single-chain magnets by far-infrared spectroscopy

Science.gov (United States)

Haas, Sabrina; Heintze, Eric; Zapf, Sina; Gorshunov, Boris; Dressel, Martin; Bogani, Lapo

2014-05-01

The far-infrared optical transmission has been studied for two lanthanide-based single-chain magnets DyPhOPh and TbPhOPh in the frequency range between 3 and 80 cm-1. The spectra were acquired at temperatures between 2 and 80 K and magnetic fields up to 6 T. Based on their magnetic field dependence in DyPhOPh two of the observed absorption lines are identified as transitions inside the crystal field split Dy3+ ground multiplet 6H15/2, coupled to the neighboring spins. In TbPhOPh one transition was observed inside the crystal-field-split Tb3+ ground multiplet 7F6. The results allow a spectroscopic investigation of the role of single-ion anisotropy and exchange in Glauber dynamics.

1.5 W green light generation by single-pass second harmonic generation of a single-frequency tapered diode laser

DEFF Research Database (Denmark)