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Sample records for antibodies attached molecular

  1. Monoclonal Antibodies Attached to Carbon Nanotube Transistors for Paclitaxel Detection

    Science.gov (United States)

    Lee, Wonbae; Lau, Calvin; Richardson, Mark; Rajapakse, Arith; Weiss, Gregory; Collins, Philip; UCI, Molecular Biology; Biochemistry Collaboration; UCI, Departments of Physics; Astronomy Collaboration

    Paclitaxel is a naturally-occurring pharmaceutical used in numerous cancer treatments, despite its toxic side effects. Partial inhibition of this toxicity has been demonstrated using weakly interacting monoclonal antibodies (3C6 and 8A10), but accurate monitoring of antibody and paclitaxel concentrations remains challenging. Here, single-molecule studies of the kinetics of antibody-paclitaxel interactions have been performed using single-walled carbon nanotube field-effect transistors. The devices were sensitized with single antibody attachments to record the single-molecule binding dynamics of paclitaxel. This label-free technique recorded a range of dynamic interactions between the antibody and paclitaxel, and it provided sensitive paclitaxel detection for pM to nM concentrations. Measurements with two different antibodies suggest ways of extending this working range and uncovering the mechanistic differences among different antibodies.

  2. Molecular-specific urokinase antibodies

    Science.gov (United States)

    Atassi, M. Zouhair (Inventor); Morrison, Dennis R. (Inventor)

    2009-01-01

    Antibodies have been developed against the different molecular forms of urokinase using synthetic peptides as immunogens. The peptides were synthesized specifically to represent those regions of the urokinase molecules which are exposed in the three-dimensional configuration of the molecule and are uniquely homologous to urokinase. Antibodies are directed against the lysine 158-isoleucine 159 peptide bond which is cleaved during activation from the single-chain (ScuPA) form to the bioactive double chain (54 KDa and 33 KDa) forms of urokinase and against the lysine 135 lysine 136 bond that is cleaved in the process of removing the alpha-chain from the 54 KDa form to produce the 33 KDa form of urokinase. These antibodies enable the direct measurement of the different molecular forms of urokinase from small samples of conditioned medium harvested from cell cultures.

  3. DEMONSTRATION OF MULTIPLE ANTIGENIC DETERMINANTS ON 'MYCOPLASMA PNEUMONIAE' ATTACHMENT PROTEIN BY MONOCLONAL ANTIBODIES

    Science.gov (United States)

    Distinct multiple antigenic determinants of the attachment protein of Mycoplasma pneumoniae have been identified by limited proteolytic cleavage using specific monoclonal antibodies. Western blots prepared from the gels containing the cleaved fragments were probed with antiserum ...

  4. Motility assays using myosin attached to surfaces through specific binding to monoclonal antibodies.

    Science.gov (United States)

    Winkelmann, D A; Bourdieu, L; Kinose, F; Libchaber, A

    1995-04-01

    We have analyzed the dependence of actin filament movement on the mode of myosin attachment to surfaces. Monoclonal antibodies that bind to three distinct sites were used to tether myosin to nitrocellulose-coated glass. One antibody reacts with an epitope on the regulatory light chain located at the head-rod junction. The other two react with sites in the rod domain, one in the S2 region near the S2-LMM hinge, and the other at the C terminus of the myosin rod. These monoclonal antibodies were used to provide increasing flexibility in the mode of attachment. Fast skeletal muscle myosin monomers were bound to the surfaces through the specific interaction with these monoclonal antibodies and the sliding movement of fluorescently labeled actin filaments analyzed by video microscopy. Each of these antibodies produced stable, myosin-coated surfaces that supported uniform movement of actin over the course of several hours. Attachment of myosin through the anti-S2 and anti-LMM monoclonal antibodies yielded a maximum velocity of 10 microns/s at 30 degrees C, whereas attachment through anti-LC2 produced a lower velocity of 4-5 microns/s. Each antibody showed a characteristic minimum myosin density below which sliding movement was no longer supported and an exponential dependence of actin filament velocity on myosin surface density below Vmax. Maximum sliding velocity was achieved over a range of myosin surface densities. Thus, the specific mode of attachment can influence the characteristic velocity of actin filament movement and the surface density needed to support movement. These data are being used to analyze the dynamics of sliding filament assays and evaluate estimates of the average number of motor molecules per unit length of actin required to support movement.

  5. Bordetella pertussis attachment to respiratory epithelial cells can be impaired by fimbriae-specific antibodies

    NARCIS (Netherlands)

    Rodriguez, ME; Hellwig, SMM; Vidakovics, MLAP; Berbers, GAM; van de Winkel, JGJ

    2006-01-01

    Bordetella pertussis attachment to host cells is a crucial step in colonization. In this study, we investigated the specificity of antibodies, induced either by vaccination or infection, capable of reducing bacterial adherence to respiratory epithelial cells. Both sera and purified anti-B. pertussis

  6. Dissociative electron attachment to CO2 produces molecular oxygen

    Science.gov (United States)

    Wang, Xu-Dong; Gao, Xiao-Fei; Xuan, Chuan-Jin; Tian, Shan Xi

    2016-03-01

    Until recently, it was widely regarded that only one reaction pathway led to the production of molecular oxygen in Earth's prebiotic primitive atmosphere: a three-body recombination reaction of two oxygen atoms and a third body that removes excess energy. However, an additional pathway has recently been observed that involves the photodissociation of CO2 on exposure to ultraviolet light. Here we demonstrate a further pathway to O2 production, again from CO2, but via dissociative electron attachment (DEA). Using anion-velocity image mapping, we provide experimental evidence for a channel of DEA to CO2 that produces O2(X3Σ-g) + C-. This observed channel coexists in the same energy range as the competitive three-body dissociation of CO2 to give O + O + C-. The abundance of low-energy electrons in interstellar space and the upper atmosphere of Earth suggests that the contributions of these pathways are significant and should be incorporated into atmospheric chemistry models.

  7. A bispecific antibody effectively neutralizes all four serotypes of dengue virus by simultaneous blocking virus attachment and fusion.

    Science.gov (United States)

    Shi, Xin; Deng, Yongqiang; Wang, Huajing; Ji, Guanghui; Tan, Wenlong; Jiang, Tao; Li, Xiaofeng; Zhao, Hui; Xia, Tian; Meng, Yanchun; Wang, Chao; Yu, Xiaojie; Yang, Yang; Li, Bohua; Qin, E-De; Dai, Jianxin; Qin, Cheng-Feng; Guo, Yajun

    2016-01-01

    Although dengue virus (DENV) infection severely threatens the health of humans, no specific antiviral drugs are currently approved for clinical use against DENV infection. Attachment and fusion are 2 critical steps for the flavivirus infection, and the corresponding functional epitopes are located at E protein domain III (E-DIII) and domain II (E-DII), respectively. Here, we constructed a bispecific antibody (DVD-1A1D-2A10) based on the 2 well-characterized anti-DENV monoclonal antibodies 1A1D-2 (1A1D) and 2A10G6 (2A10). The 1A1D antibody binds E-DIII and can block the virus attaching to the cell surface, while the 2A10 antibody binds E-DII and is able to prevent the virus from fusing with the endosomal membrane. Our data showed that DVD-1A1D-2A10 retained the antigen-binding activity of both parental antibodies. Importantly, it was demonstrated to be significantly more effective at neutralizing DENV than its parental antibodies both in vitro and in vivo, even better than the combination of them. To eliminate the potential antibody-dependent enhancement (ADE) effect, this bispecific antibody was successfully engineered to prevent Fc-γ-R interaction. Overall, we generated a bispecific anti-DENV antibody targeting both attachment and fusion stages, and this bispecific antibody broadly neutralized all 4 serotypes of DENV without risk of ADE, suggesting that it has great potential as a novel antiviral strategy against DENV. PMID:26905804

  8. Inhibition of Neisseria gonorrhoeae attachment to HeLa cells with monoclonal antibody directed against a protein II.

    OpenAIRE

    Sugasawara, R J; Cannon, J G; Black, W J; Nachamkin, I; Sweet, R L; Brooks, G F

    1983-01-01

    This study showed that a protein II (PII) of Neisseria gonorrhoeae FA1090 appeared to act as a mediator of attachment to HeLa cells. Two colony variants of FA1090 were selected. Both gonococcal variants were nonpiliated, but one contained a PII and the other did not. A monoclonal antibody (1090-10.1), which was directed against the PII, inhibited the apparent PII-mediated attachment to HeLa cells. Antibodies produced from clone 1035-4, which had no PII specificity, did not inhibit the attachm...

  9. Structural bases of coronavirus attachment to host aminopeptidase N and its inhibition by neutralizing antibodies.

    Directory of Open Access Journals (Sweden)

    Juan Reguera

    Full Text Available The coronaviruses (CoVs are enveloped viruses of animals and humans associated mostly with enteric and respiratory diseases, such as the severe acute respiratory syndrome and 10-20% of all common colds. A subset of CoVs uses the cell surface aminopeptidase N (APN, a membrane-bound metalloprotease, as a cell entry receptor. In these viruses, the envelope spike glycoprotein (S mediates the attachment of the virus particles to APN and subsequent cell entry, which can be blocked by neutralizing antibodies. Here we describe the crystal structures of the receptor-binding domains (RBDs of two closely related CoV strains, transmissible gastroenteritis virus (TGEV and porcine respiratory CoV (PRCV, in complex with their receptor, porcine APN (pAPN, or with a neutralizing antibody. The data provide detailed information on the architecture of the dimeric pAPN ectodomain and its interaction with the CoV S. We show that a protruding receptor-binding edge in the S determines virus-binding specificity for recessed glycan-containing surfaces in the membrane-distal region of the pAPN ectodomain. Comparison of the RBDs of TGEV and PRCV to those of other related CoVs, suggests that the conformation of the S receptor-binding region determines cell entry receptor specificity. Moreover, the receptor-binding edge is a major antigenic determinant in the TGEV envelope S that is targeted by neutralizing antibodies. Our results provide a compelling view on CoV cell entry and immune neutralization, and may aid the design of antivirals or CoV vaccines. APN is also considered a target for cancer therapy and its structure, reported here, could facilitate the development of anti-cancer drugs.

  10. Using engineered single-chain antibodies to correlate molecular binding properties and nanoparticle adhesion dynamics.

    Science.gov (United States)

    Haun, Jered B; Pepper, Lauren R; Boder, Eric T; Hammer, Daniel A

    2011-11-15

    Elucidation of the relationship between targeting molecule binding properties and the adhesive behavior of therapeutic or diagnostic nanocarriers would aid in the design of optimized vectors and lead to improved efficacy. We measured the adhesion of 200-nm-diameter particles under fluid flow that was mediated by a diverse array of molecular interactions, including recombinant single-chain antibodies (scFvs), full antibodies, and the avidin/biotin interaction. Within the panel of scFvs, we used a family of mutants that display a spectrum of binding kinetics, allowing us to compare nanoparticle adhesion to bond chemistry. In addition, we explored the effect of molecular size by inserting a protein linker into the scFv fusion construct and by employing scFvs that are specific for targets with vastly different sizes. Using computational models, we extracted multivalent kinetic rate constants for particle attachment and detachment from the adhesion data and correlated the results to molecular binding properties. Our results indicate that the factors that increase encounter probability, such as adhesion molecule valency and size, directly enhance the rate of nanoparticle attachment. Bond kinetics had no influence on scFv-mediated nanoparticle attachment within the kinetic range tested, however, but did appear to affect antibody/antigen and avidin/biotin mediated adhesion. We attribute this finding to a combination of multivalent binding and differences in bond mechanical strength between recombinant scFvs and the other adhesion molecules. Nanoparticle detachment probability correlated directly with adhesion molecule valency and size, as well as the logarithm of the affinity for all molecules tested. On the basis of this work, scFvs can serve as viable targeting receptors for nanoparticles, but improvements to their bond mechanical strength would likely be required to fully exploit their tunable kinetic properties and maximize the adhesion efficiency of nanoparticles that

  11. Attachments

    International Nuclear Information System (INIS)

    In this attachment to the Annual report 1999 of the Nuclear Regulatory Authority of the Slovak Republic (UJD) the economic and personnel data of the UJD, used abbreviations, as well as the International nuclear event scales - INES are presented. Professional level of staff of the UJD is influenced by the education structure of its staff, when nearly 75% of the total number of staff has a university degree. A of 31.12.1999 there were 79 employees as average calculated number. Financing of the regulator in 1999 was mainly provided from the state budget, which represented 96% of all expenditures. The total volume of expenditures for UJD activity funded from the state budget achieved as of 31.12.1999 Slovak crowns (SK) 67 067 thousands. In the main category of expenditures an amount of SK 63 499 thous. was used for current activities, and the difference of SK 3 587 thous. was used for raising capital assets. Significant increase expenditures in the evaluated year compared to the 1998 was caused by a special purpose payment made by the Slovakia into the Fund for reconstruction of the Chernobyl cover (SK 19 996 thous.) funded through the budget chapter of the regulator. In the structure of current expenditures the highest share is taken by current transfers to abroad in total of SK 22 543 thous., i.e. contribution to reconstruction of Chernobyl cover made to the EBRD and contributions to the Fund of Technical Co-operation of the IAEA. For procurement of goods and services an amount of SK 19 814 thous. was spent, of which SK 7 054 thous. was used for funding science and technology tasks which were contracted out. The decision-making process in performing state supervision forced UJD to contact out various expert opinions and studies, for which UJD paid SK 2 058 thous. in total. Other expenditures in a volume of SK 10 702 thous. represent travel expenses, goods and services for UJD, rent for offices and other inevitable expenses. Salaries of staff represented SK 15 953

  12. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Directory of Open Access Journals (Sweden)

    Atul Asati

    Full Text Available Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA

  13. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  14. Fluorescence Adherence Inhibition Assay: A Novel Functional Assessment of Blocking Virus Attachment by Vaccine-Induced Antibodies.

    Science.gov (United States)

    Asati, Atul; Kachurina, Olga; Karol, Alex; Dhir, Vipra; Nguyen, Michael; Parkhill, Robert; Kouiavskaia, Diana; Chumakov, Konstantin; Warren, William; Kachurin, Anatoly

    2016-01-01

    Neutralizing antibodies induced by vaccination or natural infection play a critically important role in protection against the viral diseases. In general, neutralization of the viral infection occurs via two major pathways: pre- and post-attachment modes, the first being the most important for such infections as influenza and polio, the latter being significant for filoviruses. Neutralizing capacity of antibodies is typically evaluated by virus neutralization assays that assess reduction of viral infectivity to the target cells in the presence of functional antibodies. Plaque reduction neutralization test, microneutralization and immunofluorescent assays are often used as gold standard virus neutralization assays. However, these methods are associated with several important prerequisites such as use of live virus requiring safety precautions, tedious evaluation procedure and long assessment time. Hence, there is a need for a robust, inexpensive high throughput functional assay that can be performed rapidly using inactivated virus, without extensive safety precautions. Herein, we report a novel high throughput Fluorescence Adherence Inhibition assay (fADI) using inactivated virus labeled with fluorescent secondary antibodies virus and Vero cells or erythrocytes as targets. It requires only few hours to assess pre-attachment neutralizing capacity of donor sera. fADI assay was tested successfully on donors immunized with polio, yellow fever and influenza vaccines. To further simplify and improve the throughput of the assay, we have developed a mathematical approach for calculating the 50% titers from a single sample dilution, without the need to analyze multi-point titration curves. Assessment of pre- and post-vaccination human sera from subjects immunized with IPOL®, YF-VAX® and 2013-2014 Fluzone® vaccines demonstrated high efficiency of the assay. The results correlated very well with microneutralization assay performed independently by the FDA Center of

  15. Molecular mechanisms of antibody-mediated neutralisation of flavivirus infection.

    Science.gov (United States)

    Pierson, Theodore C; Diamond, Michael S

    2008-01-01

    Flaviviruses are a group of positive-stranded RNA viruses that cause a spectrum of severe illnesses globally in more than 50 million individuals each year. While effective vaccines exist for three members of this group (yellow fever, Japanese encephalitis, and tick-borne encephalitis viruses), safe and effective vaccines for several other flaviviruses of clinical importance, including West Nile and dengue viruses, remain in development. An effective humoral immune response is critical for protection against flaviviruses and an essential goal of vaccine development. The effectiveness of virus-specific antibodies in vivo reflects their capacity to inhibit virus entry and spread through several mechanisms, including the direct neutralisation of virus infection. Recent advances in our understanding of the structural biology of flaviviruses, coupled with the use of small-animal models of flavivirus infection, have promoted significant advances in our appreciation of the factors that govern antibody recognition and inhibition of flaviviruses in vitro and in vivo. In this review, we discuss the properties that define the potency of neutralising antibodies and the molecular mechanisms by which they inhibit virus infection. How recent advances in this area have the potential to improve the development of safe and effective vaccines and immunotherapeutics is also addressed. PMID:18471342

  16. Highly Transient Molecular Interactions Underlie the Stability of Kinetochore–Microtubule Attachment During Cell Division

    Science.gov (United States)

    Zaytsev, Anatoly V.; Ataullakhanov, Fazly I.; Grishchuk, Ekaterina L.

    2013-01-01

    Chromosome segregation during mitosis is mediated by spindle microtubules that attach to chromosomal kinetochores with strong yet labile links. The exact molecular composition of the kinetochore–microtubule interface is not known but microtubules are thought to bind to kinetochores via the specialized microtubule-binding sites, which contain multiple microtubule-binding proteins. During prometaphase the lifetime of microtubule attachments is short but in metaphase it increases 3-fold, presumably owing to dephosphorylation of the microtubule-binding proteins that increases their affinity. Here, we use mathematical modeling to examine in quantitative and systematic manner the general relationships between the molecular properties of microtubule-binding proteins and the resulting stability of microtubule attachment to the protein-containing kinetochore site. We show that when the protein connections are stochastic, the physiological rate of microtubule turnover is achieved only if these molecular interactions are very transient, each lasting fraction of a second. This “microscopic” time is almost four orders of magnitude shorter than the characteristic time of kinetochore–microtubule attachment. Cooperativity of the microtubule-binding events further increases the disparity of these time scales. Furthermore, for all values of kinetic parameters the microtubule stability is very sensitive to the minor changes in the molecular constants. Such sensitivity of the lifetime of microtubule attachment to the kinetics and cooperativity of molecular interactions at the microtubule-binding site may hinder the accurate regulation of kinetochore–microtubule stability during mitotic progression, and it necessitates detailed experimental examination of the microtubule-binding properties of kinetochore-localized proteins. PMID:24376473

  17. Highly Transient Molecular Interactions Underlie the Stability of Kinetochore-Microtubule Attachment During Cell Division.

    Science.gov (United States)

    Zaytsev, Anatoly V; Ataullakhanov, Fazly I; Grishchuk, Ekaterina L

    2013-12-13

    Chromosome segregation during mitosis is mediated by spindle microtubules that attach to chromosomal kinetochores with strong yet labile links. The exact molecular composition of the kinetochore-microtubule interface is not known but microtubules are thought to bind to kinetochores via the specialized microtubule-binding sites, which contain multiple microtubule-binding proteins. During prometaphase the lifetime of microtubule attachments is short but in metaphase it increases 3-fold, presumably owing to dephosphorylation of the microtubule-binding proteins that increases their affinity. Here, we use mathematical modeling to examine in quantitative and systematic manner the general relationships between the molecular properties of microtubule-binding proteins and the resulting stability of microtubule attachment to the protein-containing kinetochore site. We show that when the protein connections are stochastic, the physiological rate of microtubule turnover is achieved only if these molecular interactions are very transient, each lasting fraction of a second. This "microscopic" time is almost four orders of magnitude shorter than the characteristic time of kinetochore-microtubule attachment. Cooperativity of the microtubule-binding events further increases the disparity of these time scales. Furthermore, for all values of kinetic parameters the microtubule stability is very sensitive to the minor changes in the molecular constants. Such sensitivity of the lifetime of microtubule attachment to the kinetics and cooperativity of molecular interactions at the microtubule-binding site may hinder the accurate regulation of kinetochore-microtubule stability during mitotic progression, and it necessitates detailed experimental examination of the microtubule-binding properties of kinetochore-localized proteins. PMID:24376473

  18. The second century of the antibody. Molecular perspectives in regulation, pathophysiology, and therapeutic applications.

    OpenAIRE

    Braun, J; Saxon, A; Wall, R; Morrison, S. L.

    1992-01-01

    The modern age of immunology began in 1890 with the discovery of antibodies as a major component of protective immunity. The 2nd century of the antibody begins with a focus on the molecular physiology and pathophysiology of immunoglobulin production. Numerous human variable-region antibody genes have been identified through advances in molecular cloning and anti-variable-region monoclonal antibodies. Some of these variable-region genes are now known to be involved in specific stages of B-lymp...

  19. Molecular imaging of rheumatoid arthritis by radiolabelled monoclonal antibodies: new imaging strategies to guide molecular therapies

    Energy Technology Data Exchange (ETDEWEB)

    Malviya, G.; Dierckx, R.A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Conti, F. [Rheumatology Unit, I Faculty of Medicine and Surgery, Sapienza University of Rome (Italy); Chianelli, M. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Unit of Nuclear Medicine, Regina apostolorum Hospital, Albano, Rome (Italy); Scopinaro, F. [Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy); Signore, A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, University of Groningen (Netherlands); Nuclear Medicine Department, Sapienza University of Rome, St. Andrea Hospital, Rome (Italy)

    2010-02-15

    The closing of the last century opened a wide variety of approaches for inflammation imaging and treatment of patients with rheumatoid arthritis (RA). The introduction of biological therapies for the management of RA started a revolution in the therapeutic armamentarium with the development of several novel monoclonal antibodies (mAbs), which can be murine, chimeric, humanised and fully human antibodies. Monoclonal antibodies specifically bind to their target, which could be adhesion molecules, activation markers, antigens or receptors, to interfere with specific inflammation pathways at the molecular level, leading to immune-modulation of the underlying pathogenic process. These new generation of mAbs can also be radiolabelled by using direct or indirect method, with a variety of nuclides, depending upon the specific diagnostic application. For studying rheumatoid arthritis patients, several monoclonal antibodies and their fragments, including anti-TNF-{alpha}, anti-CD20, anti-CD3, anti-CD4 and anti-E-selectin antibody, have been radiolabelled mainly with {sup 99m}Tc or {sup 111}In. Scintigraphy with these radiolabelled antibodies may offer an exciting possibility for the study of RA patients and holds two types of information: (1) it allows better staging of the disease and diagnosis of the state of activity by early detection of inflamed joints that might be difficult to assess; (2) it might provide a possibility to perform 'evidence-based biological therapy' of arthritis with a view to assessing whether an antibody will localise in an inflamed joint before using the same unlabelled antibody therapeutically. This might prove particularly important for the selection of patients to be treated since biological therapies can be associated with severe side-effects and are considerably expensive. This article reviews the use of radiolabelled mAbs in the study of RA with particular emphasis on the use of different radiolabelled monoclonal antibodies for

  20. Molecular recognition using nanotube-adsorbed polymer phases: nanotube antibodies

    Science.gov (United States)

    Zhang, Jingqing; Landry, Markita P.; Barone, Paul W.; Kim, Jong-Ho; Lin, Shangchao; Ulissi, Zachary W.; Lin, Dahua; Mu, Bin; Heller, Daniel A.; Boghossian, Ardemis A.; Hilmer, Andrew J.; Rwei, Alina; Hinckley, Allison C.; Kruss, Sebastian; Shandell, Mia A.; Nair, Nitish; Blake, Steven; Sen, Fatih; Sen, Selda; Croy, Robert G.; Li, Deyu; Yum, Kyungsuk; Ahn, Jin-Ho; Jin, Hong; Essigmann, John M.; Blankschtein, Daniel; Strano, Michael S.

    2016-01-01

    Molecular recognition is central to the design of therapeutics, chemical catalysis and sensors. Motifs for doing so most commonly involve biological structures such as antibodies and aptamers. The key to such biological recognition consists of a folded and constrained heteropolymer that, via intra-molecular forces, forms a unique three dimensional structure that creates a binding pocket or an interface able to recognize a specific molecule. In this work, we demonstrate that synthetic heteropolymers can be alternatively constrained by adsorption around a nanoparticle, and specifically a single walled carbon nanotube (SWNT), forming a corona phase and resulting in a new form of molecular recognition of specific molecules. The phenomenon is shown to be generic, with new heteropolymer recognition complexes demonstrated for three distinct examples: Riboflavin, l-thyroxine, and estradiol, each predicted using a 2D thermodynamic model of surface interactions. The dissociation constants are continuously tunable by perturbing the chemical structure of the heteropolymer. Moreover, these complexes can be used as new types of spatial-temporal sensors based on modulation of SWNT photoemission in the near-infrared, as we show by tracking riboflavin diffusion in murine macrophages. PMID:24270641

  1. Rate coefficients for low-energy electron dissociative attachment to molecular hydrogen

    Energy Technology Data Exchange (ETDEWEB)

    Horacek, J.; Houfek, K.; Cizek, M. [Charles University, Faculty of Mathematics and Physics, Prague (Czech Republic); Murakami, I.; Kato, T. [National Inst. for Fusion Science, Toki, Gifu (Japan)

    2003-02-01

    Calculation of rate constants for dissociative electron attachment to molecular hydrogen is reported. The calculation is based on an improved nonlocal resonance model of Cizek, Horacek and Domcke which takes fully into account the nonlocality of the resonance dynamics and uses potentials with correct asymptotic forms. The rate constants are calculated for all quantum numbers v and J of the target molecules and for electron temperature in the range 0-30000 K. (author)

  2. Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody.

    Directory of Open Access Journals (Sweden)

    Kai Xu

    Full Text Available The henipaviruses, represented by Hendra (HeV and Nipah (NiV viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4 was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.

  3. Crystal structure of the Hendra virus attachment G glycoprotein bound to a potent cross-reactive neutralizing human monoclonal antibody.

    Science.gov (United States)

    Xu, Kai; Rockx, Barry; Xie, Yihu; DeBuysscher, Blair L; Fusco, Deborah L; Zhu, Zhongyu; Chan, Yee-Peng; Xu, Yan; Luu, Truong; Cer, Regina Z; Feldmann, Heinz; Mokashi, Vishwesh; Dimitrov, Dimiter S; Bishop-Lilly, Kimberly A; Broder, Christopher C; Nikolov, Dimitar B

    2013-01-01

    The henipaviruses, represented by Hendra (HeV) and Nipah (NiV) viruses are highly pathogenic zoonotic paramyxoviruses with uniquely broad host tropisms responsible for repeated outbreaks in Australia, Southeast Asia, India and Bangladesh. The high morbidity and mortality rates associated with infection and lack of licensed antiviral therapies make the henipaviruses a potential biological threat to humans and livestock. Henipavirus entry is initiated by the attachment of the G envelope glycoprotein to host cell membrane receptors. Previously, henipavirus-neutralizing human monoclonal antibodies (hmAb) have been isolated using the HeV-G glycoprotein and a human naïve antibody library. One cross-reactive and receptor-blocking hmAb (m102.4) was recently demonstrated to be an effective post-exposure therapy in two animal models of NiV and HeV infection, has been used in several people on a compassionate use basis, and is currently in development for use in humans. Here, we report the crystal structure of the complex of HeV-G with m102.3, an m102.4 derivative, and describe NiV and HeV escape mutants. This structure provides detailed insight into the mechanism of HeV and NiV neutralization by m102.4, and serves as a blueprint for further optimization of m102.4 as a therapeutic agent and for the development of entry inhibitors and vaccines.

  4. Kinetics and role of antibodies against intimin β in colostrum and in serum from goat kids and longitudinal study of attaching and effacing Escherichia coli in goat kids

    OpenAIRE

    Orden, José A; De La Fuente, Ricardo; Yuste, María; Martínez-Pulgarín, Susana; Ruiz-Santa-Quiteria, José A.; Horcajo, Pilar; Contreras, Antonio; Sánchez, Antonio; Corrales, Juan C.; Domínguez-Bernal, Gustavo

    2010-01-01

    The presence of antibodies to the intimin β-binding region (Int280-β) of attaching and effacing Escherichia coli (AEEC) in serum from 20 goat kids from 2 herds, as well as in goat colostrum, was investigated by enzyme-linked immunosorbent assay. In addition, the onset and subsequent pattern of shedding of AEEC from the same goat kids over a 6-mo period was investigated. All the colostrum and serum samples tested contained antibodies against Int280-β. The association between the antibody titer...

  5. Neutralizing antibodies induced by recombinant virus-like particles of enterovirus 71 genotype C4 inhibit infection at pre- and post-attachment steps.

    Directory of Open Access Journals (Sweden)

    Zhiqiang Ku

    Full Text Available BACKGROUND: Enterovirus 71 (EV71 is a major causative agent of hand, foot and mouth disease, which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Antibodies elicited by experimental EV71 vaccines could neutralize infection in vitro and passively protect animal models from lethal challenge, indicating that neutralizing antibodies play an essential role in protection. However, how neutralizing antibodies inhibit infection in vitro remains unclear. METHODS/FINDINGS: In the present study, we explored the mechanisms of neutralization by antibodies against EV71 virus-like particles (VLPs. Recombinant VLPs of EV71 genotype C4 were produced in insect cells using baculovirus vectors. Immunization with the VLPs elicited a high-titer, EV71-specific antibody response in mice. Anti-VLP mouse sera potently neutralized EV71 infection in vitro. The neutralizing antibodies in the anti-VLP mouse sera were found to target mainly an extremely conserved epitope (FGEHKQEKDLEYGAC located at the GH loop of the VP1 protein. The neutralizing anti-VLP antisera were able to inhibit virus binding to target cells efficiently. In addition, post-attachment treatment of virus-bound cells with the anti-VLP antisera also neutralized virus infection, although the antibody concentration required was higher than that of the pre-attachment treatment. CONCLUSIONS: Collectively, our findings represent a valuable addition to the understanding of mechanisms of EV71 neutralization and have strong implications for EV71 vaccine development.

  6. Monoclonal antibody modification with chelate-linked high-molecular-weight polymers: major increases in polyvalent cation binding without loss of antigen binding

    Energy Technology Data Exchange (ETDEWEB)

    Torchilin, V.P.; Klibanov, A.L.; Nossiff, N.D.; Slinkin, M.A.; Strauss, H.W.; Haber, E.; Smirnov, V.N.; Khaw, B.A.

    1987-06-01

    Polyethyleneimine or polylysines of differing molecular sizes were substituted with either EDTA or DTPA and then with succinic acid groups. These polymers were then reacted with the amino groups on myosin-specific monoclonal antibody or its Fab using a water soluble carbodiimide. The polymer-antibody complexes were capable of binding up to 150 di- or trivalent ions per mole (Mn++, Gd , or /sup 111/In ) without attendant loss of antigen binding. The polylysine derivatives of the intact antibody were rapidly cleared and sequestered in the liver, whereas the polylysine 14-kilodalton (kd) derivative of Fab was cleared from the circulation with minimal hepatic and kidney sequestration. This differed from the biodistribution of intact antimyosin or its Fab labeled with /sup 111/In via direct attachment of DTPA to the epsilon amino group of the lysyl residues. Applications in magnetic resonance and nuclear imaging are envisioned.

  7. Binding hot-spots in an antibody-ssDNA interface: a molecular dynamics study.

    Science.gov (United States)

    Wang, Yeng-Tseng; Lee, Wen-Jay

    2012-10-30

    Simulating antigen-antibody interactions is essential for elucidating antigen-antibody mechanics. Proteins interactions are vital for elucidating antibody-ssDNA associations in immunology. Therefore, this study investigated the dissociation of the human systemic lupus erythematosus antibody-ssDNA complex structure. Dissociation (i.e. the distance between the center of mass of the ssDNA and the antibody) is also studied using the potential of mean force calculations based on molecular dynamics and the explicit water model. The MM-PBSA method is also used to prove our dissociation simulations. With 605 nanosecond molecular dynamics simulations, the results indicate that the 8 residues (i.e. Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2)), and the five inter-protein molecular hydrogen bonds may profoundly impact the antibody-ssDNA interaction, a finding which may be useful for protein engineering of this antibody-ssDNA structure. Experimental binding affinity of this antibody-ssDNA complex equals 7.00 kcal mol(-1). Our dissociation binding affinity is 7.96 ± 0.33 kcal mol(-1) and MM-PBSA binding affinity is 9.12 ± 1.65 kcal mol(-1), which is close to the experimental value. Additionally, the 8 residues Gly44 (HCDR2), Asn54 (HCDR2), Arg98 (HCDR3), Tyr100 (HCDR3), Asp101 (HCDR3), Tyr32 (LCDR1), Tyr49 (LCDR2) and Asn50 (LCDR2) may play a more significant role in developing bioactive antibody analogues. PMID:23079742

  8. Single Neutralizing Monoclonal Antibodies Targeting the VP1 GH Loop of Enterovirus 71 Inhibit both Virus Attachment and Internalization during Viral Entry

    Science.gov (United States)

    Ku, Zhiqiang; Ye, Xiaohua; Shi, Jinping; Wang, Xiaoli

    2015-01-01

    ABSTRACT Antibodies play a critical role in immunity against enterovirus 71 (EV71). However, how EV71-specific antibodies neutralize infections remains poorly understood. Here we report the working mechanism for a group of three monoclonal antibodies (MAbs) that potently neutralize EV71. We found that these three MAbs (termed D5, H7, and C4, respectively) recognize the same conserved neutralizing epitope within the VP1 GH loop of EV71. Single MAbs in this group, exemplified by D5, could inhibit EV71 infection in cell cultures at both the pre- and postattachment stages in a cell type-independent manner. Specifically, MAb treatment resulted in the blockade of multiple steps of EV71 entry, including virus attachment, internalization, and subsequent uncoating and RNA release. Furthermore, we show that the D5 and C4 antibodies can interfere with EV71 binding to its key receptors, including heparan sulfate, SCARB2, and PSGL-1, thus providing a possible explanation for the observed multi-inhibitory function of the MAbs. Collectively, our study unravels the mechanism of neutralization by a unique group of anti-EV71 MAbs targeting the conserved VP1 GH loop. The findings should enhance our understanding of MAb-mediated immunity against enterovirus infections and accelerate the development of MAb-based anti-EV71 therapeutic drugs. IMPORTANCE Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease (HFMD), which has caused significant morbidities and mortalities in young children. Neither a vaccine nor an antiviral drug is available. Neutralizing antibodies are major protective components in EV71 immunity. Here, we unraveled an unusual mechanism of EV71 neutralization by a group of three neutralizing monoclonal antibodies (MAbs). All of these MAbs bound the same conserved epitope located at the VP1 GH loop of EV71. Interestingly, mechanistic studies showed that single antibodies in this MAb group could block EV71 attachment and internalization during

  9. On the dissociative electron attachment as a potential source of molecular hydrogen in irradiated liquid water

    Energy Technology Data Exchange (ETDEWEB)

    Cobut, V.; Jay-Gerin, J.-P.; Frongillo, Y. [Sherbrooke Univ., PQ (Canada). Faculte de Medecine; Patau, J.P. [Toulouse-3 Univ., 31 (France)

    1996-02-01

    In the radiolysis of liquid water, different mechanisms for the formation of molecular hydrogen (H{sub 2}) are involved at different times after the initial energy disposition. It has been suggested that the contributions of the e{sub aq}{sup -} + e{sub aq}{sup -}, H + e{sub aq}{sup -} and H + H reactions between hydrated electrons (e{sub aq}{sup -}) and hydrogen atoms in the spurs are not sufficient to account for all of the observed H{sub 2} yield (0.45 molecules/100 eV) on the microsecond time scale. Addressing the question of the origin of an unscavengeable H{sub 2} yield of 0.15 molecules/100 eV produced before spur expansion, we suggest that the dissociative capture of the so-called vibrationally-relaxing electrons by H{sub 2}O molecules is a possible pathway for the formation of part of the initial H{sub 2} yield. Comparison of recent dissociative-electron-attachment H{sup -}-anion yield-distribution measurements from amorphous H{sub 2}O films with the energy spectrum of vibrationally-relaxing electrons in irradiated liquid water, calculated by Monte Carlo simulations, plays in favor of this hypothesis. (author).

  10. Formation of carbon chain molecular anions by radiative electron attachment and their destruction by photodetachment

    Science.gov (United States)

    Khamesian, Marjan; Douguet, Nicolas; Raoult, Maurice; Dulieu, Olivier; Kokoouline, Viatcheslav

    2016-05-01

    Several negative ions Cn H- (n = 4 , 6 , 8), Cn N- (n = 1 , 3 , 5) have been recently observed in the interstellar medium (ISM). A possible mechanism of formation is radiative electron attachment (REA). In this study we develop a first principle theoretical approach to study the REA and apply the approach to the formation of the negative molecular ions CN-, C2 H-, C3 N-, C4 H-, C5 N-, C6 H-, and C8 H-. The theoretical approach is based on the UK R-matrix calculations. Cross sections and rate coefficients for formation of these ions by REA to the corresponding neutral radicals are calculated. There is no experimental data on REA of these ions. However, using a similar approach we have also calculated cross sections for photodetachment of the negative ions and compared the obtained results with available experimental data. The good agreement with photodetachment experimental data provides a confirmation that the REA cross sections obtained in this study is also reliable. NSF Grant PHYS-1506391.

  11. Molecular Pathways: Immune Checkpoint Antibodies and their Toxicities.

    Science.gov (United States)

    Cousin, Sophie; Italiano, Antoine

    2016-09-15

    The emergence of immune checkpoint inhibitors for solid tumor treatments represents a major oncologic advance. Since the approval of ipilimumab, a cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, for the treatment of metastatic melanoma, many drugs, especially those targeting PD-1/PD-L1, have demonstrated promising antitumor effects in many types of cancer. By reactivating the immune system, these immunotherapies have led to the development of new toxicity profiles, also called immune-related adverse events (irAE). IrAEs can involve many organ systems, and their management is radically different from that of cytotoxic drugs; irAEs require immunosuppressive treatments, such as corticoids or TNFα antibody. In addition, the occurrence of irAEs has raised significant questions. Here, we summarize progress that has been made toward answering these questions, focusing on (i) the impact of immunotherapy dose on irAE occurrence, (ii) the correlation between irAE and patient outcome, (iii) the safety of immune checkpoint inhibitors in patients already treated for autoimmune disease, and (iv) the suspected effect on tumor growth of steroids used for the management of irAEs. Clin Cancer Res; 22(18); 4550-5. ©2016 AACR.

  12. Molecular phylogenetic analysis of attached Ulvaceae species and free-floating Enteromorpha from Qingdao coasts in 2007

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Based on the sequence data of the nuclear ribosomal DNA internal transcribed spacer (ITS) 1, 5.8 S, and ITS 2, the molecular phylogeny was analyzed on Ulvaceae species collected from Qingdao coasts in summer of 2007, including 15 attached Ulva and Enteromorpha samples from 10 locations and 10 free-floating Enteromorpha samples from seven locations. The result supported the monophyly of all free-floating Enteromorpha samples, implying the unialgal composition of the free-floating Enteromorpha, and the attached Ulvaceae species from Qingdao coasts were grouped into other five clades, suggesting that they were not the biogeographic origin of the free-floating Enteromorpha in that season.

  13. Molecular basis of high viscosity in concentrated antibody solutions: Strategies for high concentration drug product development.

    Science.gov (United States)

    Tomar, Dheeraj S; Kumar, Sandeep; Singh, Satish K; Goswami, Sumit; Li, Li

    2016-01-01

    Effective translation of breakthrough discoveries into innovative products in the clinic requires proactive mitigation or elimination of several drug development challenges. These challenges can vary depending upon the type of drug molecule. In the case of therapeutic antibody candidates, a commonly encountered challenge is high viscosity of the concentrated antibody solutions. Concentration-dependent viscosity behaviors of mAbs and other biologic entities may depend on pairwise and higher-order intermolecular interactions, non-native aggregation, and concentration-dependent fluctuations of various antibody regions. This article reviews our current understanding of molecular origins of viscosity behaviors of antibody solutions. We discuss general strategies and guidelines to select low viscosity candidates or optimize lead candidates for lower viscosity at early drug discovery stages. Moreover, strategies for formulation optimization and excipient design are also presented for candidates already in advanced product development stages. Potential future directions for research in this field are also explored. PMID:26736022

  14. Molecular Evolution of Antibody Cross-Reactivity for Two Subtypes of Type a Botulinum Neurotoxin

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Rodriguez, C.; Levy, R.; Arndt, J.W.; Forsyth, C.M.; Razai, A.; Lou, J.; Geren, I.; Stevens, R.C.; Marks, J.D.; /UC, San Francisco /Scripps Res. Inst.

    2007-07-09

    Broadening antibody specificity without compromising affinity should facilitate detection and neutralization of toxin and viral subtypes. We used yeast display and a co-selection strategy to increase cross-reactivity of a single chain (sc) Fv antibody to botulinum neurotoxin type A (BoNT/A). Starting with a scFv that binds the BoNT/A1 subtype with high affinity (136 pM) and the BoNT/A2 subtype with low affinity (109 nM), we increased its affinity for BoNT/A2 1,250-fold, to 87 pM, while maintaining high-affinity binding to BoNT/A1 (115 pM). To find the molecular basis for improved cross-reactivity, we determined the X-ray co-crystal structures of wild-type and cross-reactive antibodies complexed to BoNT/A1 at resolutions up to 2.6 A, and measured the thermodynamic contribution of BoNT/A1 and A2 amino acids to wild-type and cross-reactive antibody binding. The results show how an antibody can be engineered to bind two different antigens despite structural differences in the antigen-antibody interface and may provide a general strategy for tuning antibody specificity and cross-reactivity.

  15. Plastic Antibodies for Cosmetics: Molecularly Imprinted Polymers Scavenge Precursors of Malodors.

    Science.gov (United States)

    Nestora, Sofia; Merlier, Franck; Beyazit, Selim; Prost, Elise; Duma, Luminita; Baril, Bérangère; Greaves, Andrew; Haupt, Karsten; Tse Sum Bui, Bernadette

    2016-05-17

    Molecularly imprinted polymers (MIPs) are synthetic antibody mimics capable of specific molecular recognition. Advantageously, they are more stable, easy to tailor for a given application and less expensive than antibodies. These plastic antibodies are raising increasing interest and one relatively unexplored domain in which they could outplay these advantages particularly well is cosmetics. Here, we present the use of a MIP as an active ingredient of a cosmetic product, for suppressing body odors. In a dermo-cosmetic formulation, the MIP captures selectively the precursors of malodorous compounds, amidst a multitude of other molecules present in human sweat. These results pave the way to the fabrication of a novel generation of MIPs with improved selectivities in highly complex aqueous environments, and should be applicable to biotechnological and biomedical areas as well. PMID:27060928

  16. Bacterial Attachment to Polymeric Materials Correlates with Molecular Flexibility and Hydrophilicity

    OpenAIRE

    Sanni, Olutoba; Chang, Chien-Yi; Anderson, Daniel G.; Langer, Robert; Davies, Martyn C.; Williams, Philip M; Williams, Paul; Alexander, Morgan R.; Hook, Andrew L.

    2014-01-01

    A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This...

  17. Structural analysis and molecular modeling of two antitrichosanthin IgE clones from phage antibody library

    Institute of Scientific and Technical Information of China (English)

    LIZONGDONG; YURENYUAN; 等

    1997-01-01

    Recently we constructed a murine IgE phage surface display library and screened out two IgE (Fab) clones with specific binding activity to Trichosanthin (TCS).In this work,the Vε and Vκ genes of the two clones were sequenced and their putative germline gene usages were studied.On the basis of the known 3D structure of Trichosanthin and antibody,molecular modeling was carried out to study the antigen-antibody interaction.The possible antigenic determinant sites on the surface of TCS recognized by both the clones were analyzed,and the reaction forces between TCS and two Fab fragments were also analyzed respectively.

  18. Bacterial attachment to polymeric materials correlates with molecular flexibility and hydrophilicity.

    Science.gov (United States)

    Sanni, Olutoba; Chang, Chien-Yi; Anderson, Daniel G; Langer, Robert; Davies, Martyn C; Williams, Philip M; Williams, Paul; Alexander, Morgan R; Hook, Andrew L

    2015-04-01

    A new class of material resistant to bacterial attachment has been discovered that is formed from polyacrylates with hydrocarbon pendant groups. In this study, the relationship between the nature of the hydrocarbon moiety and resistance to bacteria is explored, comparing cyclic, aromatic, and linear chemical groups. A correlation is shown between bacterial attachment and a parameter derived from the partition coefficient and the number of rotatable bonds of the materials' pendant groups. This correlation is applicable to 86% of the hydrocarbon pendant moieties surveyed, quantitatively supporting the previous qualitative observation that bacteria are repelled from poly(meth)acrylates containing a hydrophilic ester group when the pendant group is both rigid and hydrophobic. This insight will help inform and predict the further development of polymers resistant to bacterial attachment. PMID:25491266

  19. Molecular evolution of broadly neutralizing Llama antibodies to the CD4-binding site of HIV-1.

    Directory of Open Access Journals (Sweden)

    Laura E McCoy

    2014-12-01

    Full Text Available To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols.

  20. Molecular Evolution of Broadly Neutralizing Llama Antibodies to the CD4-Binding Site of HIV-1

    Science.gov (United States)

    McCoy, Laura E.; Rutten, Lucy; Frampton, Dan; Anderson, Ian; Granger, Luke; Bashford-Rogers, Rachael; Dekkers, Gillian; Strokappe, Nika M.; Seaman, Michael S.; Koh, Willie; Grippo, Vanina; Kliche, Alexander; Verrips, Theo; Kellam, Paul; Fassati, Ariberto; Weiss, Robin A.

    2014-01-01

    To date, no immunization of humans or animals has elicited broadly neutralizing sera able to prevent HIV-1 transmission; however, elicitation of broad and potent heavy chain only antibodies (HCAb) has previously been reported in llamas. In this study, the anti-HIV immune responses in immunized llamas were studied via deep sequencing analysis using broadly neutralizing monoclonal HCAbs as a guides. Distinct neutralizing antibody lineages were identified in each animal, including two defined by novel antibodies (as variable regions called VHH) identified by robotic screening of over 6000 clones. The combined application of five VHH against viruses from clades A, B, C and CRF_AG resulted in neutralization as potent as any of the VHH individually and a predicted 100% coverage with a median IC50 of 0.17 µg/ml for the panel of 60 viruses tested. Molecular analysis of the VHH repertoires of two sets of immunized animals showed that each neutralizing lineage was only observed following immunization, demonstrating that they were elicited de novo. Our results show that immunization can induce potent and broadly neutralizing antibodies in llamas with features similar to human antibodies and provide a framework to analyze the effectiveness of immunization protocols. PMID:25522326

  1. Use of Heteropolymeric Monoclonal Antibodies to Attach Antigens to the C3b Receptor of Human Erythrocytes: A Potential Therapeutic Treatment

    Science.gov (United States)

    Taylor, Ronald P.; Sutherland, William M.; Reist, Craig J.; Webb, Donna J.; Wright, Eleanor L.; Labuguen, Ronald H.

    1991-04-01

    We have prepared bispecific, cross-linked monoclonal antibodies (heteropolymers) with specificity for both targeted antigens and the human erythrocyte (RBC) complement receptor. These heteropolymers facilitate binding of target antigens (human IgG and dinitrophenylated bovine γ globulin) to human RBCs under conditions that either allow or preclude complement activation. Quantitative analyses of this binding agree well with the number of complement receptors per RBC. In vitro "whole-blood" model experiments indicate heteropolymer-facilitated binding of antigens to RBCs is rapid and stable at 37^circC. It may be possible to extend these prototype experiments to the in vivo situation and use heteropolymer-attached RBCs for the safe and rapid binding, neutralization, and removal from the circulation of pathogenic antigens associated with infectious disease.

  2. Molecular aspects of antibody-antigen interactions : size reduction of a herpes simplex virus neutralizing antibody and its antigen

    NARCIS (Netherlands)

    Schellekens, Gerardus Antonius

    1996-01-01

    Antibody molecules, produced as a response against foreign substances, interact with their antigen in a very specific manner. Antibodies with a predetermined specificity (monoclonal antibodies) can be produced and are widely used in medicine and science as indicator molecules. Genetic engineering of

  3. Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins.

    Science.gov (United States)

    Kavanagh, Owen; Elliott, Christopher T; Campbell, Katrina

    2015-04-01

    Rapid immunoanalytical screening of food and environmental samples for small molecular weight (hapten) biotoxin contaminations requires the production of antibody reagents that possess the requisite sensitivity and specificity. To date animal-derived polyclonal (pAb) and monoclonal (mAb) antibodies have provided the binding element of the majority of these assays but recombinant antibodies (rAb) isolated from in vitro combinatorial phage display libraries are an exciting alternative due to (1) circumventing the need for experimental animals, (2) speed of production in commonly used in vitro expression systems and (3) subsequent molecular enhancement of binder performance. Short chain variable fragments (scFv) have been the most commonly employed rAb reagents for hapten biotoxin detection over the last two decades but antibody binding fragments (Fab) and single domain antibodies (sdAb) are increasing in popularity due to increased expression efficiency of functional binders and superior resistance to solvents. rAb-based immunochromatographic assays and surface plasmon resonance (SPR) biosensors have been reported to detect sub-regulatory levels of fungal (mycotoxins), marine (phycotoxins) and aquatic biotoxins in a wide range of food and environmental matrices, however this technology has yet to surpass the performances of the equivalent mAb- and pAb-based formats. As such the full potential of rAb technology in hapten biotoxin detection has yet to be achieved, but in time the inherent advantages of engineered rAb are set to provide the next generation of ultra-high performing binder reagents for the rapid and specific detection of hapten biotoxins.

  4. Progress in the development of immunoanalytical methods incorporating recombinant antibodies to small molecular weight biotoxins.

    Science.gov (United States)

    Kavanagh, Owen; Elliott, Christopher T; Campbell, Katrina

    2015-04-01

    Rapid immunoanalytical screening of food and environmental samples for small molecular weight (hapten) biotoxin contaminations requires the production of antibody reagents that possess the requisite sensitivity and specificity. To date animal-derived polyclonal (pAb) and monoclonal (mAb) antibodies have provided the binding element of the majority of these assays but recombinant antibodies (rAb) isolated from in vitro combinatorial phage display libraries are an exciting alternative due to (1) circumventing the need for experimental animals, (2) speed of production in commonly used in vitro expression systems and (3) subsequent molecular enhancement of binder performance. Short chain variable fragments (scFv) have been the most commonly employed rAb reagents for hapten biotoxin detection over the last two decades but antibody binding fragments (Fab) and single domain antibodies (sdAb) are increasing in popularity due to increased expression efficiency of functional binders and superior resistance to solvents. rAb-based immunochromatographic assays and surface plasmon resonance (SPR) biosensors have been reported to detect sub-regulatory levels of fungal (mycotoxins), marine (phycotoxins) and aquatic biotoxins in a wide range of food and environmental matrices, however this technology has yet to surpass the performances of the equivalent mAb- and pAb-based formats. As such the full potential of rAb technology in hapten biotoxin detection has yet to be achieved, but in time the inherent advantages of engineered rAb are set to provide the next generation of ultra-high performing binder reagents for the rapid and specific detection of hapten biotoxins. PMID:25716465

  5. Attachment of a Genetically Engineered Antibody to a Carbon Nanotube Transistor for Detection of Prostate Cancer Biomarkers

    Science.gov (United States)

    Lerner, Mitchell; Dailey, Jennifer; Goldsmith, Brett; Robinson, Matthew; Johnson, A. T. Charlie

    2011-03-01

    We have developed a novel detection method for osteopontin (OPN) by attaching an engineered single chain variable fragment (scFv) protein with high binding affinity for OPN to a carbon nanotube transistor. Osteopontin is a potential new biomarker for prostate cancer; its presence in humans is already associated with several forms of cancer, arthritis, osteoporosis and stress. Prostate cancer is the most commonly diagnosed cancer and second leading cause of cancer deaths among American men and as such represents a major public health issue. Detection of early-stage cancer often results in successful treatment, with long term disease-free survival in 60-90% of patients. Electronic transport measurements are used to detect the presence of OPN in solution at clinically relevant concentrations.

  6. Resolving self-association of a therapeutic antibody by formulation optimization and molecular approaches.

    Science.gov (United States)

    Casaz, Paul; Boucher, Elisabeth; Wollacott, Rachel; Pierce, Brian G; Rivera, Rachel; Sedic, Maja; Ozturk, Sadettin; Thomas, William D; Wang, Yang

    2014-01-01

    A common challenge encountered during development of high concentration monoclonal antibody formulations is preventing self-association. Depending on the antibody and its formulation, self-association can be seen as aggregation, precipitation, opalescence or phase separation. Here we report on an unusual manifestation of self-association, formation of a semi-solid gel or "gelation." Therapeutic monoclonal antibody C4 was isolated from human B cells based on its strong potency in neutralizing bacterial toxin in animal models. The purified antibody possessed the unusual property of forming a firm, opaque white gel when it was formulated at concentrations >30 mg/mL and the temperature was electrostatic interaction between IgG monomers. A comparison of the C4 amino acid sequences to consensus germline sequences revealed differences in framework regions. A C4 variant in which the framework sequence was restored to the consensus germline sequence did not gel at 100 mg/mL at temperatures as low as 1°C. Additional genetic analysis was used to predict the key residue(s) involved in the gelation. Strikingly, a single substitution in the native antibody, replacing heavy chain glutamate 23 with lysine (E23K), was sufficient to prevent gelation. These results indicate that the framework region is involved in intermolecular interactions. The temperature dependence of gelation may be related to conformational changes near glutamate 23 or the regions it interacts with. Molecular engineering of the framework can be an effective approach to resolve the solubility issues of therapeutic antibodies. PMID:25484044

  7. Molecular mechanism of SCARB2-mediated attachment and uncoating of EV71.

    Science.gov (United States)

    Dang, Minghao; Wang, Xiangxi; Wang, Quan; Wang, Yaxin; Lin, Jianping; Sun, Yuna; Li, Xuemei; Zhang, Liguo; Lou, Zhiyong; Wang, Junzhi; Rao, Zihe

    2014-09-01

    Unlike the well-established picture for the entry of enveloped viruses, the mechanism of cellular entry of non-enveloped eukaryotic viruses remains largely mysterious. Picornaviruses are representative models for such viruses, and initiate this entry process by their functional receptors. Here we present the structural and functional studies of SCARB2, a functional receptor of the important human enterovirus 71 (EV71). SCARB2 is responsible for attachment as well as uncoating of EV71. Differences in the structures of SCARB2 under neutral and acidic conditions reveal that SCARB2 undergoes a pivotal pH-dependent conformational change which opens a lipid-transfer tunnel to mediate the expulsion of a hydrophobic pocket factor from the virion, a pre-requisite for uncoating. We have also identified the key residues essential for attachment to SCARB2, identifying the canyon region of EV71 as mediating the receptor interaction. Together these results provide a clear understanding of cellular attachment and initiation of uncoating for enteroviruses.

  8. Application of Targeted Molecular and Material Property Optimization to Bacterial Attachment-Resistant (Meth)acrylate Polymers.

    Science.gov (United States)

    Adlington, Kevin; Nguyen, Nam T; Eaves, Elizabeth; Yang, Jing; Chang, Chien-Yi; Li, Jianing; Gower, Alexandra L; Stimpson, Amy; Anderson, Daniel G; Langer, Robert; Davies, Martyn C; Hook, Andrew L; Williams, Paul; Alexander, Morgan R; Irvine, Derek J

    2016-09-12

    Developing medical devices that resist bacterial attachment and subsequent biofilm formation is highly desirable. In this paper, we report the optimization of the molecular structure and thus material properties of a range of (meth)acrylate copolymers which contain monomers reported to deliver bacterial resistance to surfaces. This optimization allows such monomers to be employed within novel coatings to reduce bacterial attachment to silicone urinary catheters. We show that the flexibility of copolymers can be tuned to match that of the silicone catheter substrate, by copolymerizing these polymers with a lower Tg monomer such that it passes the flexing fatigue tests as coatings upon catheters, that the homopolymers failed. Furthermore, the Tg values of the copolymers are shown to be readily estimated by the Fox equation. The bacterial resistance performance of these copolymers were typically found to be better than the neat silicone or a commercial silver containing hydrogel surface, when the monomer feed contained only 25 v% of the "hit" monomer. The method of initiation (either photo or thermal) was shown not to affect the bacterial resistance of the copolymers. Optimized synthesis conditions to ensure that the correct copolymer composition and to prevent the onset of gelation are detailed. PMID:27461341

  9. A strategy of designing the ligand of antibody affinity chromatography based on molecular dynamics simulation.

    Science.gov (United States)

    Dai, Lu; Li, Weikang; Sun, Fei; Li, Baizhi; Li, Hongrui; Zhang, Hongxing; Zheng, Qingchuan; Liang, Chongyang

    2016-09-01

    Designing affinity ligands has always been the development focus of affinity chromatography. Previous antibody affinity ligand designs were mostly based on the crystal structure of protein A (UniProt code number: P38507), and the antibody-binding domains were modified according to the properties of amino acid residues. Currently, more effective bioinformatic prediction and experimental validation has been used to improve the design of antibody affinity ligands. In the present study, the complex crystal structure (the domain D of protein A and the Fab segment of IgM, PDB code: 1DEE) was used as the model. The vital site that inhibits the binding between domain D and IgM was estimated by means of molecular dynamics (MD) simulation, then MM-GBSA calculations were used to design a mutant of domain D (K46E) for improving affinity on the above vital site. The binding analysis using Biacore showed the association and dissociation parameters of K46E mutant that were optimized with IgM. The affinity increase of K46E mutant preferred for IgM, the affinity order is K46E tetramer (KD=6.02×10(-9)M)>K46E mutant (KD=6.66×10(-8)M)>domain D (KD=2.17×10(-7)M). Similar results were obtained when the optimized ligands were immobilized to the chromatography medium. A complete designing strategy was validated in this study, which will provide a novel insight into designing new ligands of antibody affinity chromatography media.

  10. A strategy of designing the ligand of antibody affinity chromatography based on molecular dynamics simulation.

    Science.gov (United States)

    Dai, Lu; Li, Weikang; Sun, Fei; Li, Baizhi; Li, Hongrui; Zhang, Hongxing; Zheng, Qingchuan; Liang, Chongyang

    2016-09-01

    Designing affinity ligands has always been the development focus of affinity chromatography. Previous antibody affinity ligand designs were mostly based on the crystal structure of protein A (UniProt code number: P38507), and the antibody-binding domains were modified according to the properties of amino acid residues. Currently, more effective bioinformatic prediction and experimental validation has been used to improve the design of antibody affinity ligands. In the present study, the complex crystal structure (the domain D of protein A and the Fab segment of IgM, PDB code: 1DEE) was used as the model. The vital site that inhibits the binding between domain D and IgM was estimated by means of molecular dynamics (MD) simulation, then MM-GBSA calculations were used to design a mutant of domain D (K46E) for improving affinity on the above vital site. The binding analysis using Biacore showed the association and dissociation parameters of K46E mutant that were optimized with IgM. The affinity increase of K46E mutant preferred for IgM, the affinity order is K46E tetramer (KD=6.02×10(-9)M)>K46E mutant (KD=6.66×10(-8)M)>domain D (KD=2.17×10(-7)M). Similar results were obtained when the optimized ligands were immobilized to the chromatography medium. A complete designing strategy was validated in this study, which will provide a novel insight into designing new ligands of antibody affinity chromatography media. PMID:27524303

  11. Molecular Dynamics in Dissociative Electron Attachment to CO probed by Velocity Slice Imaging

    CERN Document Server

    Nag, Pamir

    2014-01-01

    Angular distribution and kinetic energy distribution of O$^-$/CO ions formed by dissociative electron attachment process has been studied for 9, 9.5, 10, 10.5, 11, 11.5 eV incident electron energies using time sliced velocity map imaging spectrometer. The angular distribution of the ions formed with different kinetic energy for same incident electron energy are studied separately. The kinetic energy distribution is energy dependent and a second peak appears after 10.5 eV incident electron energy. We found the existence of two processes leading to the O$^-$ formation, $e^- +\\text{CO}(^1\\Sigma^+) \\rightarrow \\text{CO}^{-*} \\rightarrow \\text{O}^- (^2P) + \\text{C}^* (^3P) $ and $e^- + \\text{CO}(^1\\Sigma^+) \\rightarrow \\text{CO}^{-*} \\rightarrow \\text{O}^- (^2P) + \\text{C}^* (^1D)$. We have investigated the symmetry of intermediate state for different incident electron energies and found the presence of $\\Sigma$ and $\\Pi$ state at 9, 9.5 and 10 eV. At 10.5, 11 and 11.5 eV in the first process $\\Sigma, \\, \\Pi$ and ...

  12. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    Science.gov (United States)

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer. PMID:26961312

  13. Fab(nimotuzumab)-HYNIC-99mTc: Antibody Fragmentation for Molecular Imaging Agents.

    Science.gov (United States)

    Calzada, Victoria; García, María Fernanda; Alonso-Martínez, Luis Michel; Camachoc, Ximena; Goicochea, Enzo; Fernández, Marcelo; Castillo, Abmel Xiques; Díaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Montaña, René Leyva; Alonso, Omar; Gambini, Juan Pablo; Cabral, Pablo

    2016-01-01

    Finally, fast blood clearance nimotuzumab is a humanized monoclonal antibody that recognise, with high specific affinity, the epidermal growth factor receptor (EGF-R) which play an important role in the growth process associated with many solid tumors. In this work, the whole antibody was digested with papain in order to generate a Fab fragment, derivatized with NHS-HYNIC-Tfa and radiolabel with technetium-99m (99mTc) as a potential agent of molecular imaging of cancer. Both, whole and fragment radiolabels were in-vivo and in-vitro characterized. Radiolabeling conditions with Tricine as coligand and quality controls were assessed to confirm the integrity of the labeled fragment. Biodistribution and imaging studies in normal and spontaneous adenocarcinoma mice were performed at different times to determine the in-vivo characteristics of the radiolabel fragment. Tumor localization was visualized by conventional gamma camera imaging studies, and the results were compared with the whole antibody. Also, an immunoreactivity assay was carried out for both. The results showed clearly the integrity of the nimotuzumab fragment and the affinity by the receptor was verified. Fab(nimotuzumab)-HYNIC was obtained with high purity and a simple strategy of radiolabeling was performed. Finally, a fast blood clearance was observed in the biodistribution studies increasing the tumor uptake of Fab(nimotuzumab)- HYNIC-99mTc over time, with tumor/muscle ratios of 3.81 ± 0.50, 5.16 ± 1.97 and 6.32 ± 1.98 at 1 h, 4 h and 24 h post injection. Urinary excretion resulted in 32.89 ± 3.91 %ID eliminated at 24 h. Scintigraphy images showed uptake in the tumor and the activity in non-target organs was consistent with the biodistribution data at the same time points. Hence, these preliminary results showed important further characteristic of Fab(nimotuzumab)-HYNIC-99mTc as a molecular imaging agent of cancer.

  14. Electron-attachment processes

    International Nuclear Information System (INIS)

    Topics covered include: (1) modes of production of negative ions, (2) techniques for the study of electron attachment processes, (3) dissociative electron attachment to ground-state molecules, (4) dissociative electron attachment to hot molecules (effects of temperature on dissociative electron attachment), (5) molecular parent negative ions, and (6) negative ions formed by ion-pair processes and by collisions of molecules with ground state and Rydberg atoms

  15. [Molecular dynamics of immune complex of photoadduct-containing DNA with Fab-Anti-DNA antibody fragment].

    Science.gov (United States)

    Akberova, N I; Zhmurov, A A; Nevzorova, T A; Litvinov, R I

    2016-01-01

    Antibodies to DNA play an important role in the pathogenesis of autoimmune diseases. The elucidation of structural mechanisms of both the antigen recognition and the interaction of anti-DNA antibodies with DNA will help to understand the role of DNA-containing immune complexes in various pathologies and can provide a basis for new treatment modalities. Moreover, the DNA-antibody complex is an analog of specific intracellular DNA-protein interactions. In this work, we used in silico molecular dynamic simulations of bimolecular complexes of the dsDNA segment containing the Fab fragment of an anti-DNA antibody to obtain the detailed thermodynamic and structural characteristics of dynamic intermolecular interactions. Using computationally modified crystal structure of the Fab-DNA complex (PDB ID: 3VW3), we studied the equilibrium molecular dynamics of the 64M-5 antibody Fab fragment associated with the dsDNA fragment containing the thymine dimer, the product of DNA photodamage. Amino acid residues that constitute paratopes and the complementary nucleotide epitopes for the Fab-DNA construct were identified. Stacking and electrostatic interactions were found to play the main role in mediating the most specific antibody-dsDNA contacts, while hydrogen bonds were less significant. These findings may shed light on the formation and properties of pathogenic anti-DNA antibodies in autoimmune diseases, such as systemic lupus erythematosus associated with skin photosensitivity and DNA photodamage.

  16. Neonatal molecular pathologies induced by maternal anti-Ro and anti-La antibodies

    Directory of Open Access Journals (Sweden)

    Herrera-Esparza R

    2015-08-01

    Full Text Available Maternal antinuclear antibodies with anti-Ro or anti-La specificity might be pathogenic to the fetus and could induce molecular neonatal pathologies, such as neonatal lupus (NL with or without congenital heart block (CHB. The cutaneous manifestations of neonatal lupus appear at birth or a few weeks later, and skin lesions may persist for weeks. While CHB is characterized by intrauterine bradycardia or low heart rates at birth and may persist for months, depending on the degree of blockage. Clinical and experimental data demonstrated that anti-Ro and anti-La autoantibodies functionally inhibit L-type calcium channels and induce abnormalities in electrical conduction of the cardiac myocytes. It has been 38 years since the first clinical description of CHB. Presently, the pathophysiology of CHB has been clarified through clinical and basic research studies.

  17. Effect of different hapten-carrier conjugation ratios and molecular orientations on antibody affinity against a peptide antigen

    DEFF Research Database (Denmark)

    Pedersen, M. K.; Sørensen, Nanna Skall; Heegaard, Peter M. H.;

    2006-01-01

    -based assay systems and in deciding whether a vaccine-induced antibody response will be protective. With ovalbumin as a carrier protein and a peptide (7.2NY) representing a 19 ammo acid sequence from the E. coli-derived Verotoxin 2e as a model hapten we investigated whether it was possible to influence...... the affinity and titre of antibodies raised against the hapten using different conjugation ratios and orientations. The peptide was coupled to ovalbumin in four Conjugation ratios and two molecular orientations - terminal and central - and the Conjugates were verified by mass spectrometry. Mice were immunised......, the molecular orientation of the Coupled peptide has a major effect on the anti-peptide antibody titres induced....

  18. Diverse redox-active molecules bearing O-, S-, or Se-terminated tethers for attachment to silicon in studies of molecular information storage.

    Science.gov (United States)

    Balakumar, Arumugham; Lysenko, Andrey B; Carcel, Carole; Malinovskii, Vladimir L; Gryko, Daniel T; Schweikart, Karl-Heinz; Loewe, Robert S; Yasseri, Amir A; Liu, Zhiming; Bocian, David F; Lindsey, Jonathan S

    2004-03-01

    A molecular approach to information storage employs redox-active molecules tethered to an electroactive surface. Attachment of the molecules to electroactive surfaces requires control over the nature of the tether (linker and surface attachment group). We have synthesized a collection of redox-active molecules bearing different linkers and surface anchor groups in free or protected form (hydroxy, mercapto, S-acetylthio, and Se-acetylseleno) for attachment to surfaces such as silicon, germanium, and gold. The molecules exhibit a number of cationic oxidation states, including one (ferrocene), two [zinc(II)porphyrin], three [cobalt(II)porphyrin], or four (lanthanide triple-decker sandwich compound). Electrochemical studies of monolayers of a variety of the redox-active molecules attached to Si(100) electrodes indicate that molecules exhibit a regular mode of attachment (via a Si-X bond, X = O, S, or Se), relatively homogeneous surface organization, and robust reversible electrochemical behavior. The acetyl protecting group undergoes cleavage during the surface deposition process, enabling attachment to silicon via thio or seleno groups without handling free thiols or selenols. PMID:14986994

  19. Fluorescent competitive assay for melamine using dummy molecularly imprinted polymers as antibody mimics

    Institute of Scientific and Technical Information of China (English)

    DU Xin-wei; JIN Mao-jun; ZHENG Lu-fei; ZHANG Yan-xin; SHE Yong-xin; LIU Guang-yang; ZHAO Feng-nian; WANG Jing; WANG Shan-shan; JIN Fen; SHAO Hua

    2016-01-01

    A lfuorescent competitive assay for melamine was ifrst developed utilizing dummy molecularly imprinted polymers (DMIPs) as artiifcial antibodies. This method is based on the competition between lfuorescent substances and the unlabeled analyte for binding sites in synthesized DMIPs and the decreased binding of lfuorescent substances to DMIPs due to increased concentrations of melamine in the solutions. DMIPs for melamine were synthesized under a hot water bath in the pres-ence of the initiator azobisisobutyronitrile (AIBN) using 2,4-diamino-6-methyl-1,3,5-triazine (DAMT) as a dummy template, methacrylic acid (MAA) as a functional monomer, and ethylene glycol dimethacrylate (EGDMA) as a crosslinking agent. The adsorption capacity and selectivity of DMIPs for melamine were evaluated by the isothermal adsorption curve and Scatchard analysis. The evaluation results showed that the synthesized DMIPs had speciifc recognition sites for melamine and the maximum adsorption amount was 1066.33 μg g–1. Later, 5-(4,6-dichlorotriazinyl) amino lfuorescein (DTAF) with a triazine ring, which slightly resembles melamine, was selected as the lfuorescent substance. The lfuorescent competitive assay using DMIPs as the antibody mimics was ifnaly established by selecting and optimizing the reaction solvents, DMIPs amount, DTAF concentration, and incubation time. The optimal detection system showed a linear response within range of 0.05–40 mg L–1 and the limit of detection (LOD) was 1.23 μg L–1. It was successfuly applied to the detection of melamine in spiked milk samples with satisfactory recoveries (71.9 to 86.3%). According to the comparative analysis, the result of optimized lfuorescent competitive assay revealed excelent agreement with the HPLC-MS/MS result for melamine.

  20. Protein attachment onto silica surfaces--a survey of molecular fundamentals, resulting effects and novel preventive strategies in CE.

    Science.gov (United States)

    Stutz, Hanno

    2009-06-01

    This review addresses the fundamentals governing the adsorption of individual protein molecules onto the surface of fused-silica capillaries, the protein aggregation to adsorbate clusters and their final accretion to monolayers with subsequent stratification to protein multilayers. The attention in CE protein separation has primarily been focused on (i) tuning the BGE including the buffer type, ionic strength, pH and additives, (ii) tailored post-rinse procedures to detach adhered protein residues and (iii) the optimization of capillary wall shielding in order to reduce protein attachment. Improvements in protein separation as well as related adverse effects are mainly discussed on the basis of parameters known to become deteriorated in case of protein adhesion, e.g. repeatability of the EOF and of migration times, peak width, theoretical plate numbers, resolution and asymmetry factor. However, knowledge of the molecular principles controlling protein adsorption onto silica surfaces is indispensable for separation optimization. Furthermore, it facilitates troubleshooting and the interpretation of undesired concomitant phenomena. This review comprehensively discusses protein adsorption models derived from surface chemistry primarily in terms of their relevance for CE, clearly showing that the adsorption process in its complexity is only partially revealed by models, which address single or binary protein solutions. In a further section theoretical concepts and surface models are related to surface phenomena encountered in CE. The final part of the review surveys recent concepts for prevention of protein adhesion, thereby addressing capillary treatment, favorable buffer types, dynamic and adhesive semi-permanent coating strategies covering the literature from 2000-2008.

  1. Molecular characterization of monoclonal antibodies that inhibit acetylcholinesterase by targeting the peripheral site and backdoor region.

    Directory of Open Access Journals (Sweden)

    Yves Bourne

    Full Text Available The inhibition properties and target sites of monoclonal antibodies (mAbs Elec403, Elec408 and Elec410, generated against Electrophorus electricus acetylcholinesterase (AChE, have been defined previously using biochemical and mutagenesis approaches. Elec403 and Elec410, which bind competitively with each other and with the peptidic toxin inhibitor fasciculin, are directed toward distinctive albeit overlapping epitopes located at the AChE peripheral anionic site, which surrounds the entrance of the active site gorge. Elec408, which is not competitive with the other two mAbs nor fasciculin, targets a second epitope located in the backdoor region, distant from the gorge entrance. To characterize the molecular determinants dictating their binding site specificity, we cloned and sequenced the mAbs; generated antigen-binding fragments (Fab retaining the parental inhibition properties; and explored their structure-function relationships using complementary x-ray crystallography, homology modeling and flexible docking approaches. Hypermutation of one Elec403 complementarity-determining region suggests occurrence of antigen-driven selection towards recognition of the AChE peripheral site. Comparative analysis of the 1.9Å-resolution structure of Fab408 and of theoretical models of its Fab403 and Fab410 congeners evidences distinctive surface topographies and anisotropic repartitions of charges, consistent with their respective target sites and inhibition properties. Finally, a validated, data-driven docking model of the Fab403-AChE complex suggests a mode of binding at the PAS that fully correlates with the functional data. This comprehensive study documents the molecular peculiarities of Fab403 and Fab410, as the largest peptidic inhibitors directed towards the peripheral site, and those of Fab408, as the first inhibitor directed toward the backdoor region of an AChE and a unique template for the design of new, specific modulators of AChE catalysis.

  2. Molecular interactions and trafficking of influenza A virus polymerase proteins analyzed by specific monoclonal antibodies

    Energy Technology Data Exchange (ETDEWEB)

    MacDonald, Leslie A.; Aggarwal, Shilpa; Bussey, Kendra A.; Desmet, Emily A.; Kim, Baek; Takimoto, Toru, E-mail: toru_takimoto@urmc.rochester.edu

    2012-04-25

    The influenza polymerase complex composed of PA, PB1 and PB2, plays a key role in viral replication and pathogenicity. Newly synthesized components must be translocated to the nucleus, where replication and transcription of viral genomes take place. Previous studies suggest that while PB2 is translocated to the nucleus independently, PA and PB1 subunits could not localize to the nucleus unless in a PA-PB1 complex. To further determine the molecular interactions between the components, we created a panel of 16 hybridoma cell lines, which produce monoclonal antibodies (mAbs) against each polymerase component. We showed that, although PB1 interacts with both PA and PB2 individually, nuclear localization of PB1 is enhanced only when co-expressed with PA. Interestingly, one of the anti-PA mAbs reacted much more strongly with PA when co-expressed with PB1. These results suggest that PA-PB1 interactions induce a conformational change in PA, which could be required for its nuclear translocation.

  3. A quantum chemical study from a molecular perspective: ionization and electron attachment energies for species often used to fabricate single-molecule junctions

    CERN Document Server

    Baldea, Ioan

    2015-01-01

    The accurate determination of the lowest electron attachment ($EA$) and ionization ($IP$) energies for molecules embedded in molecular junctions is important for correctly estimating, \\emph{e.g.}, the magnitude of the currents ($I$) or the biases ($V$) where an $I-V$-curve exhibits a significant non-Ohmic behavior. Benchmark calculations for the lowest electron attachment and ionization energies of several typical molecules utilized to fabricate single-molecule junctions characterized by n-type conduction (4,4'-bipyridine, 1,4-dicyanobenzene, and 4,4'-dicyano-1,1'-biphenyl) and p-type conduction (benzenedithiol, biphenyldithiol, hexanemonothiol, and hexanedithiol] based on the EOM-CCSD (equation-of-motion coupled-cluster singles and doubles) state-of-the-art method of quantum chemistry are presented. They indicate significant differences from the results obtained within current approaches to molecular transport. The present study emphasizes that, in addition to a reliable quantum chemical method, basis sets m...

  4. Bovine Colostrum Contains Immunoglobulin G Antibodies against Intimin, EspA, and EspB and Inhibits Hemolytic Activity Mediated by the Type Three Secretion System of Attaching and Effacing Escherichia coli▿

    Science.gov (United States)

    Vilte, Daniel A.; Larzábal, Mariano; Cataldi, Ángel A.; Mercado, Elsa C.

    2008-01-01

    Enterohemorrhagic Escherichia coli (EHEC) is the main cause of hemolytic-uremic syndrome, an endemic disease in Argentina which had an incidence in 2005 of 13.9 cases per 100,000 children younger than 5 years old. Cattle appear to be a major reservoir of EHEC, and a serological response to EHEC antigens has been demonstrated in natural and experimental infections. In the current study, antibodies against proteins implicated in EHEC's ability to form attaching and effacing lesions, some of which are exported to the host cell via a type three secretion system (TTSS), were identified in bovine colostrum by Western blot analysis. Twenty-seven (77.0%) of the 35 samples examined contained immunoglobulin G (IgG) antibodies against the three proteins assayed in this study: EspA, EspB, and the carboxy-terminal 280 amino acids of γ-intimin, an intimin subtype associated mainly with O157:H7 and O145:H- serotypes. Every colostrum sample was able to inhibit, in a range between 45.9 and 96.7%, the TTSS-mediated hemolytic activity of attaching and effacing E. coli. The inhibitory effect was partially mediated by IgG and lactoferrin. In conclusion, we found that early colostrum from cows contains antibodies, lactoferrin, and other unidentified substances that impair TTSS function in attaching and effacing E. coli strains. Bovine colostrum might act by reducing EHEC colonization in newborn calves and could be used as a prophylactic measure to protect non-breast-fed children against EHEC infection in an area of endemicity. PMID:18562563

  5. Antibody to a molecular marker of cell position inhibits synapse formation in retina.

    OpenAIRE

    Trisler, D.; Bekenstein, J; Daniels, M P

    1986-01-01

    A topographic gradient of TOP molecules in retina can be used to identify neuron position. Antibody to TOP from hybridoma cells that were injected into in vivo embryo eyes diffused into the retina and bound in a topographic gradient of [antibody.TOP] ([Ab.TOP]) complexes. Synapse formation in retina was inhibited in the presence of anti-TOP antibody. This suggests that TOP is involved in synapse formation and that recognition of position by neurons is necessary for normal synapse formation.

  6. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    International Nuclear Information System (INIS)

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection

  7. Molecular determinants of dengue virus 2 envelope protein important for virus entry in FcγRIIA-mediated antibody-dependent enhancement of infection

    Energy Technology Data Exchange (ETDEWEB)

    Chotiwan, Nunya; Roehrig, John T. [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States); Schlesinger, Jacob J. [Department of Medicine, University of Rochester, Rochester, NY 14642 (United States); Blair, Carol D. [Arthropod-borne and Infectious Diseases Laboratory, Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, CO 80523 (United States); Huang, Claire Y.-H., E-mail: yxh0@cdc.gov [Arboviral Diseases Branch, Division of Vector-Borne Disease, Centers for Disease Control and Prevention, Fort Collins, CO 80521 (United States)

    2014-05-15

    Antibody-dependent enhancement (ADE) of infection may cause severe illness in patients suffering a secondary infection by a heterologous dengue virus (DENV) serotype. During ADE of infection, cross-reactive non- or poorly-neutralizing antibodies form infectious virus-Ab complexes with the newly infecting serotype and enhance virus infection by binding to the Fcγ receptors (FcγR) on FcγR-bearing cells. In this study, we determined that molecular determinants of DENV2 envelope protein critical for virus entry during non-ADE infection are also required for ADE infection mediated by FcγRIIA, and binding of virus-Ab complexes with FcγRIIA alone is not sufficient for ADE of infection. The FcγRIIA mainly plays an auxiliary role in concentrating the virus–Ab complex to the cell surface, and other primary cellular receptors are required for virus entry. Understanding the viral entry pathway in ADE of DENV infection will greatly facilitate rational designs of anti-viral therapeutics against severe dengue disease associated with ADE. - Highlights: • KKK305/307/310 in DENV2 E-DIII is critical for virus attachment in ADE and non-ADE infection. • Binding of DENV2–Ab complex with FcγRII alone is not sufficient for virus entry in ADE infection. • Other primary receptors were required for DENV2 internalization during FcγRII–mediated ADE. • G104 and L135 of DENV2 E are critical for virus-mediated membrane fusion. • DENV2 virus-mediated membrane fusion is required for both ADE and non-ADE infection.

  8. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    Science.gov (United States)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  9. Indocyanine green as effective antibody conjugate for intracellular molecular targeted photodynamic therapy

    Science.gov (United States)

    Wang, Sijia; Hüttmann, Gereon; Rudnitzki, Florian; Diddens-Tschoeke, Heyke; Zhang, Zhenxi; Rahmanzadeh, Ramtin

    2016-07-01

    The fluorescent dye indocyanine green (ICG) is clinically approved and has been applied for ophthalmic and intraoperative angiography, measurement of cardiac output and liver function, or as contrast agent in cancer surgery. Though ICG is known for its photochemical effects, it has played a minor role so far in photodynamic therapy or techniques for targeted protein-inactivation. Here, we investigated ICG as an antibody-conjugate for the selective inactivation of the protein Ki-67 in the nucleus of cells. Conjugates of the Ki-67 antibody TuBB-9 with different amounts of ICG were synthesized and delivered into HeLa and OVCAR-5 cells through conjugation to the nuclear localization sequence. Endosomal escape of the macromolecular antibodies into the cytoplasm was optically triggered by photochemical internalization with the photosensitizer BPD. The second light irradiation at 690 nm inactivated Ki-67 and subsequently caused cell death. Here, we show that ICG as an antibody-conjugate can be an effective photosensitizing agent. Best effects were achieved with 1.8 ICG molecules per antibody. Conjugated to antibodies, the ICG absorption peaks vary proportionally with concentration. The absorption of ICG above 650 nm within the optical window of tissue opens the possibility of selective Ki-67 inactivation deep inside of tissues.

  10. The neurobiology of attachment.

    Science.gov (United States)

    Insel, T R; Young, L J

    2001-02-01

    It is difficult to think of any behavioural process that is more intrinsically important to us than attachment. Feeding, sleeping and locomotion are all necessary for survival, but humans are, as Baruch Spinoza famously noted, "a social animal" and it is our social attachments that we live for. Over the past decade, studies in a range of vertebrates, including humans, have begun to address the neural basis of attachment at a molecular, cellular and systems level. This review describes some of the important insights from this work.

  11. Distribution of lifetimes of kinetochore-microtubule attachments:interplay of energy landscape, molecular motors and microtubule (de-)polymerization

    CERN Document Server

    Sharma, Ajeet K; Chowdhury, Debashish

    2013-01-01

    Before a cell divides into two daughter cells, the chromosomes are replicated resulting in two sister chromosomes embracing each other. Each sister chromosome is bound to a separate proteinous structure, called kinetochore (kt), that captures the tip of a filamentous protein, called microtubule (MT). Two oppositely oriented MTs pull the two kts attached to two sister chromosomes thereby pulling the two sisters away from each other. Here we theoretically study an even simpler system, namely an isolated kt coupled to a single MT; this system mimics an {\\it in-vitro} experiment where a single kt-MT attachment is reconstituted using purified extracts from budding yeast. Our models not only account for the experimentally observed "catch-bond-like" behavior of the kt-MT coupling, but also make new predictions on the probability distribution of the lifetimes of the attachments. In principle, our new predictions can be tested by analyzing the data collected in the {\\it in-vitro} experiments provided the experiment is...

  12. Product Attachment

    OpenAIRE

    Mugge, R.

    2007-01-01

    The topic of this doctoral research is the concept of product attachment for ordinary consumer durables. Product attachment is defined as the strength of the emotional bond a consumer experiences with a specific product. Specifically, the research investigated how this bond develops over time and the relationship between product attachment and product lifetime. In addition, we studied which determinants may affect the strength of the emotional bond with products and uncovered the role of the ...

  13. Product Attachment

    NARCIS (Netherlands)

    Mugge, R.

    2007-01-01

    The topic of this doctoral research is the concept of product attachment for ordinary consumer durables. Product attachment is defined as the strength of the emotional bond a consumer experiences with a specific product. Specifically, the research investigated how this bond develops over time and th

  14. Prevalence and first molecular characterization of Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, in Rhipicephalus sanguineus ticks attached to dogs from Egypt

    Directory of Open Access Journals (Sweden)

    Mohamed W. Ghafar

    2012-04-01

    Full Text Available PCR targeting 16S rRNA gene integrated with sequence analysis were performed to investigate the prevalence and the molecular identity of Anaplasma phagocytophilum in Egyptian Rhipicephalus sanguineus ticks attached to dogs. A total of 413 adult and nymphal R. sanguineus ticks were collected while attached to 72 free-roaming dogs from four locations (Imbaba, Boulaq, Haram, Monib in Giza Governorate, Egypt. DNA was successfully extracted from 401 specimens (133 nymphs and 268 adults. The overall prevalence rate was 13.7% and adult ticks showed a significantly higher infection rate (16.4% compared to nymphs (8.3%. Sequence comparisons of 218-bp showed that detected organism belongs to A. phagocytophilum. The sequence showed 99.1% similarity (2 nucleotide differences with some strains described as human pathogens and with that detected in the established tick vectors. Phylogenetic analysis placed the bacteria on a separate branch with that found in R. annulatus from Egypt (DQ379972 (99.5% similarity. Our variant strain was designated as A. phagocytophilum-Ghafar-EGY (AB608266. This report is the first molecular characterization of A. phagocytophilum in R. sanguineus in Egypt, suggesting that this tick species may act as a competent vector for a variant strain of human granulocytic anaplasmosis agent.

  15. An Immunosensor Based on Antibody Binding Fragments Attached to Gold Nanoparticles for the Detection of Peptides Derived from Avian Influenza Hemagglutinin H5

    Directory of Open Access Journals (Sweden)

    Urszula Jarocka

    2014-08-01

    Full Text Available This paper concerns the development of an immunosensor for detection of peptides derived from avian influenza hemagglutinin H5. Its preparation consists of successive gold electrode modification steps: (i modification with 1,6-hexanedithiol and gold colloidal nanoparticles; (ii immobilization of antibody-binding fragments (Fab’ of anti-hemagglutinin H5 monoclonal antibodies Mab 6-9-1 via S-Au covalent bonds; and (iii covering the remaining free space on the electrode surfaces with bovine serum albumin. The interactions between Fab’ fragments and hemagglutinin (HA variants have been explored with electrochemical impedance spectroscopy (EIS in the presence of [Fe(CN6]3−/4− as an electroactive marker. The immunosensor was able to recognize three different His-tagged variants of recombinant hemagglutinin from H5N1 viruses: H1 subunit (17–340 residues of A/swan/Poland/305-135V08/2006, the long HA (17–530 residues A/Bar-headed Goose/Qinghai/12/2005 and H1 subunit (1–345 residues of A/Vietnam/1194/2004. The strongest response has been observed for the long variant with detection limit of 2.2 pg/mL and dynamic range from 4.0 to 20.0 pg/mL.

  16. Electrosynthesis and binding properties of molecularly imprinted poly-o-phenylenediamine as artificial antibodies for electroanalysis of myoglobin.

    Science.gov (United States)

    Shumyantseva, V V; Bulko, T V; Sigolaeva, L V; Kuzikov, A V; Shatskaya, M A; Archakov, A I

    2015-01-01

    Molecularly imprinted poly-o-phenylenediamine with template myoglobin molecules (i.e., polymeric antibodies to myoglobin, molecularly imprinted polymer, MIP) was synthesized via electropolymerization. Electropolymerization, washing, and the interaction of the polymeric antibodies with myoglobin was examined by square wave voltammetry and microgravimetry. The analysis of myoglobin was carried out through direct electrochemical detection of the reduction peak of Fe(3+) of the hemeprotein on screen-printed graphite electrodes modified by the MIP. According to the electrochemical analysis, MIP surfaces demonstrated remarkably higher ability to bind the protein compared to that of surfaces prepared by the same route under the same conditions but in the absence of myoglobin (surfaces of the non-imprinted polymer, NIP). The imprinting factor I max(MIP)/I max(NIP) was found to be 2-4. The equilibrium dissociation constant K d of the interaction of myoglobin with MIP electrodes was evaluated as (2.4 ± 0.5) × 10(-8) M. The lower detection limit of myoglobin by a MIP sensor was determined as 0.5 × 10(-9) M, the range of detectable concentrations being 10(-9)-10(-5) M.

  17. Interaction analysis of HIV-1 antibody 2G12 and Man9GlcNAc2 ligand: Theoretical calculations by fragment molecular orbital and MD methods

    Science.gov (United States)

    Koyama, Yuka; Ueno-Noto, Kaori; Takano, Keiko

    2013-07-01

    In HIV-1 infection, human antibody 2G12 is capable of recognizing the high-mannose glycans on the HIV-1 surface glycoprotein, gp120. To investigate the ligand binding mechanisms of antibody 2G12 with glycans aiming for the contribution to the medications, we carried out classical molecular dynamics (MD) simulations and ab initio fragment molecular orbital (FMO) calculations on the antibody 2G12 complex with its high-mannose ligand. We found that Mannose D1 of the ligand had the largest binding affinity with the antibody, which was well consistent with experimental reports. Furthermore, significant roles of Mannose 4 and 4‧ in the ligand binding were theoretically indicated.

  18. Structural and molecular basis for Ebola virus neutralization by protective human antibodies.

    Science.gov (United States)

    Misasi, John; Gilman, Morgan S A; Kanekiyo, Masaru; Gui, Miao; Cagigi, Alberto; Mulangu, Sabue; Corti, Davide; Ledgerwood, Julie E; Lanzavecchia, Antonio; Cunningham, James; Muyembe-Tamfun, Jean Jacques; Baxa, Ulrich; Graham, Barney S; Xiang, Ye; Sullivan, Nancy J; McLellan, Jason S

    2016-03-18

    Ebola virus causes hemorrhagic fever with a high case fatality rate for which there is no approved therapy. Two human monoclonal antibodies, mAb100 and mAb114, in combination, protect nonhuman primates against all signs of Ebola virus disease, including viremia. Here, we demonstrate that mAb100 recognizes the base of the Ebola virus glycoprotein (GP) trimer, occludes access to the cathepsin-cleavage loop, and prevents the proteolytic cleavage of GP that is required for virus entry. We show that mAb114 interacts with the glycan cap and inner chalice of GP, remains associated after proteolytic removal of the glycan cap, and inhibits binding of cleaved GP to its receptor. These results define the basis of neutralization for two protective antibodies and may facilitate development of therapies and vaccines.

  19. Structural, electrochemical, and photophysical properties of a molecular shuttle attached to an acid-terminated self-assembled monolayer

    NARCIS (Netherlands)

    Cecchet, F; Rudolf, P; Rapino, S; Margotti, M; Paolucci, F; Baggerman, J; Kay, ER; Wong, JKY; Leigh, DA; Kay, Euan R.; Wong, Jenny K.Y.; Brouwer, A.M.

    2004-01-01

    A benzylic amide macrocycle containing a pyridine moiety (macrocycle 2) and a related benzylic amide macrocycle-based molecular shuttle (naphthalimide rotaxane) with two pyridine moieties on the macrocyclic unit were grafted onto a self-assembled monolayer (SAM) of 11-mercaptoundecanoic acid (11-MUA

  20. In vivo recombination as a tool to generate molecular diversity in phage antibody libraries.

    Science.gov (United States)

    Sblattero, D; Lou, J; Marzari, R; Bradbury, A

    2001-06-01

    The creation of diversity in populations of polypeptides has become an important tool in the derivation of polypeptides with useful characteristics. This requires efficient methods to create diversity coupled with methods to select polypeptides with desired properties. In this review we describe the use of in vivo recombination as a powerful way to generate diversity. The novel principles for the recombination process and several applications of this process for the creation of phage antibody libraries are described. The advantage and disadvantages are discussed and possible future exploitation presented.

  1. Attachment of an anti-MUC1 monoclonal antibody to 5-FU loaded BSA nanoparticles for active targeting of breast cancer cells.

    Science.gov (United States)

    Kouchakzadeh, Hasan; Shojaosadati, Seyed Abbas; Mohammadnejad, Javad; Paknejad, Malihe; Rasaee, Mohammad Javad

    2012-01-01

    With PR81 as a murine monoclonal antibody (mAb) that was prepared against the human breast cancer, the MUC1 receptor specific targeting is possible. In this study, PR81-conjugated bovine serum albumin (BSA) nanoparticles loaded with anticancer drug 5-fluorouracil (5-FU) were developed. Enzyme linked immunosorbant assay (ELISA) results showed high immunoreactivity of PR81 mAb conjugated to nanoparticles towards MUC1 related peptide or native cancerous MUC1 and almost no cross-reaction to non-specific proteins. In vitro experiments were performed to determine the ability of this new drug delivery system on overcoming MCF-7 breast cancer cells in comparison with four other systems. The results revealed that these cell-type specific drug loaded nanoparticles could achieve more cell death as compared to when the 5-FU was used with no carriers. Stability studies of produced drug delivery system proved high immunoreactivity of conjugated PR81 even after 11 days of storage in room temperature.

  2. In Vivo Molecular Imaging to Diagnose and Subtype Tumors through Receptor-Targeted Optically Labeled Monoclonal Antibodies

    Directory of Open Access Journals (Sweden)

    Yoshinori Koyama

    2007-12-01

    Full Text Available Molecular imaging of cell surface receptors can potentially diagnose tumors based on their distinct expression profiles. Using multifilter spectrally resolved optical imaging with three fluorescently labeled antibodies, we simultaneously imaged three different cell surface receptors to distinguish tumor types noninvasively. We selected tumors overexpressing different subtypes of EGFR receptor: HER-1 (A431 and HER-2 (NIH3T3/HER2+, or interleukin-2 receptor α-subunit receptor (IL-2Rα; SP2/Tac. After tumor establishment, a cocktail of three fluorescently labeled monoclonal antibodies was injected: cetuximab-Cy5 (targeting HER-1, trastuzumab-Cy7 (HER-2, daclizumab-AIexaFluor700 (IL-2Ra. Optical fluorescence imaging was performed after 24 hours with both a red filter set and three successive filter sets (yellow, red, deep red. Spectrally resolved imaging of 10 mice clearly distinguished A431, NIH3T3/HER2+, SP2-Tac tumors based on their distinct optical spectra. Three-filter sets significantly increased the signal-to-background ratio compared to a single-filter set by reducing the background signal, thus significantly improving the differentiation of each of the receptors targeted (P < .022. In conclusion, following multifilter spectrally resolved imaging, different tumor types can be simultaneously distinguished and diagnosed in vivo. Multiple filter sets increase the signal-to-noise ratio by substantially reducing the background signal, may allow more optical dyes to be resolved within the narrow limits of the near-infrared spectrum.

  3. Epitope mapping of monoclonal antibody HPT-101: a study combining dynamic force spectroscopy, ELISA and molecular dynamics simulations

    Science.gov (United States)

    Stangner, Tim; Angioletti-Uberti, Stefano; Knappe, Daniel; Singer, David; Wagner, Carolin; Hoffmann, Ralf; Kremer, Friedrich

    2015-12-01

    By combining enzyme-linked immunosorbent assay (ELISA) and optical tweezers-assisted dynamic force spectroscopy (DFS), we identify for the first time the binding epitope of the phosphorylation-specific monoclonal antibody (mAb) HPT-101 to the Alzheimer's disease relevant peptide tau[pThr231/pSer235] on the level of single amino acids. In particular, seven tau isoforms are synthesized by replacing binding relevant amino acids by a neutral alanine (alanine scanning). From the binding between mAb HPT-101 and the alanine-scan derivatives, we extract specific binding parameters such as bond lifetime {τ }0, binding length {x}{ts}, free energy of activation {{Δ }}G (DFS) and affinity constant {K}{{a}} (ELISA, DFS). Based on these quantities, we propose criteria to identify essential, secondary and non-essential amino acids, being representative of the antibody binding epitope. The obtained results are found to be in full accord for both experimental techniques. In order to elucidate the microscopic origin of the change in binding parameters, we perform molecular dynamics (MD) simulations of the free epitope in solution for both its parent and modified form. By taking the end-to-end distance {d}{{E}-{{E}}} and the distance between the α-carbons {d}{{C}-{{C}}} of the phosphorylated residues as gauging parameters, we measure how the structure of the epitope depends on the type of substitution. In particular, whereas {d}{{C}-{{C}}} is sometimes conserved between the parent and modified form, {d}{{E}-{{E}}} strongly changes depending on the type of substitution, correlating well with the experimental data. These results are highly significant, offering a detailed microscopic picture of molecular recognition.

  4. Broad-specificity immunoassay for O,O-diethyl organophosphorus pesticides: Application of molecular modeling to improve assay sensitivity and study antibody recognition

    Science.gov (United States)

    A monoclonal antibody (MAb) against 4-(diethoxyphosphorothioyloxy)benzoic acid (hapten 1) was raised and used to develop a broad-specificity competitive indirect enzyme-linked immunosorbent assay (ciELISA) for 14 O,O-diethyl organophosphorus pesticides (OPs). Computer-assisted molecular modeling was...

  5. Metal Oxide Nanosensors Using Polymeric Membranes, Enzymes and Antibody Receptors as Ion and Molecular Recognition Elements

    Directory of Open Access Journals (Sweden)

    Magnus Willander

    2014-05-01

    Full Text Available The concept of recognition and biofunctionality has attracted increasing interest in the fields of chemistry and material sciences. Advances in the field of nanotechnology for the synthesis of desired metal oxide nanostructures have provided a solid platform for the integration of nanoelectronic devices. These nanoelectronics-based devices have the ability to recognize molecular species of living organisms, and they have created the possibility for advanced chemical sensing functionalities with low limits of detection in the nanomolar range. In this review, various metal oxides, such as ZnO-, CuO-, and NiO-based nanosensors, are described using different methods (receptors of functionalization for molecular and ion recognition. These functionalized metal oxide surfaces with a specific receptor involve either a complex formation between the receptor and the analyte or an electrostatic interaction during the chemical sensing of analytes. Metal oxide nanostructures are considered revolutionary nanomaterials that have a specific surface for the immobilization of biomolecules with much needed orientation, good conformation and enhanced biological activity which further improve the sensing properties of nanosensors. Metal oxide nanostructures are associated with certain unique optical, electrical and molecular characteristics in addition to unique functionalities and surface charge features which shows attractive platforms for interfacing biorecognition elements with effective transducing properties for signal amplification. There is a great opportunity in the near future for metal oxide nanostructure-based miniaturization and the development of engineering sensor devices.

  6. Molecular recognition of antibody (IgG) by cellular Fc receptor (FcRI).

    Science.gov (United States)

    Burton, D R; Jefferis, R; Partridge, L J; Woof, J M

    1988-11-01

    Earlier studies from this and other laboratories have provided indirect evidence for the involvement of the C gamma 2 domain of human IgG in the binding of IgG to the high affinity monocyte Fc receptor (FcRI). Two approaches have been used to extend these studies and to further localize the site of interaction on human IgG. Firstly, monoclonal antibodies (MAbs) directed against different epitopes on IgG were assayed for their capacity to inhibit the binding of radiolabelled IgG to human monocytes or U937 cells. The capacity of the MAbs to interact with their respective epitopes on FcR-bound IgG was also studied using indirect radiobinding and immunofluorescence assays. Secondly, a number of IgGs from several different species and fragments of human IgGs were assayed for their ability to inhibit the binding of radiolabelled IgG to human monocytes. The amino acid sequences of those IgGs exhibiting relatively tight, intermediate or weak binding to monocyte FcRs were compared. On the basis of these studies a possible monocyte FcR-binding site on human IgG is postulated, involving the lower hinge region of IgG (residues Leu 234-Ser 239) with possible involvement of the nearby N-proximal bend and two beta-strands (Gly 316-Lys 338). PMID:2975762

  7. Rational design of viscosity reducing mutants of a monoclonal antibody: Hydrophobic versus electrostatic inter-molecular interactions

    Science.gov (United States)

    Nichols, Pilarin; Li, Li; Kumar, Sandeep; Buck, Patrick M; Singh, Satish K; Goswami, Sumit; Balthazor, Bryan; Conley, Tami R; Sek, David; Allen, Martin J

    2015-01-01

    High viscosity of monoclonal antibody formulations at concentrations ≥100 mg/mL can impede their development as products suitable for subcutaneous delivery. The effects of hydrophobic and electrostatic intermolecular interactions on the solution behavior of MAB 1, which becomes unacceptably viscous at high concentrations, was studied by testing 5 single point mutants. The mutations were designed to reduce viscosity by disrupting either an aggregation prone region (APR), which also participates in 2 hydrophobic surface patches, or a negatively charged surface patch in the variable region. The disruption of an APR that lies at the interface of light and heavy chain variable domains, VH and VL, via L45K mutation destabilized MAB 1 and abolished antigen binding. However, mutation at the preceding residue (V44K), which also lies in the same APR, increased apparent solubility and reduced viscosity of MAB 1 without sacrificing antigen binding or thermal stability. Neutralizing the negatively charged surface patch (E59Y) also increased apparent solubility and reduced viscosity of MAB 1, but charge reversal at the same position (E59K/R) caused destabilization, decreased solubility and led to difficulties in sample manipulation that precluded their viscosity measurements at high concentrations. Both V44K and E59Y mutations showed similar increase in apparent solubility. However, the viscosity profile of E59Y was considerably better than that of the V44K, providing evidence that inter-molecular interactions in MAB 1 are electrostatically driven. In conclusion, neutralizing negatively charged surface patches may be more beneficial toward reducing viscosity of highly concentrated antibody solutions than charge reversal or aggregation prone motif disruption. PMID:25559441

  8. Molecular signatures of hemagglutinin stem-directed heterosubtypic human neutralizing antibodies against influenza A viruses.

    Directory of Open Access Journals (Sweden)

    Yuval Avnir

    2014-05-01

    Full Text Available Recent studies have shown high usage of the IGHV1-69 germline immunoglobulin gene for influenza hemagglutinin stem-directed broadly-neutralizing antibodies (HV1-69-sBnAbs. Here we show that a major structural solution for these HV1-69-sBnAbs is achieved through a critical triad comprising two CDR-H2 loop anchor residues (a hydrophobic residue at position 53 (Ile or Met and Phe54, and CDR-H3-Tyr at positions 98±1; together with distinctive V-segment CDR amino acid substitutions that occur in positions sparse in AID/polymerase-η recognition motifs. A semi-synthetic IGHV1-69 phage-display library screen designed to investigate AID/polη restrictions resulted in the isolation of HV1-69-sBnAbs that featured a distinctive Ile52Ser mutation in the CDR-H2 loop, a universal CDR-H3 Tyr at position 98 or 99, and required as little as two additional substitutions for heterosubtypic neutralizing activity. The functional importance of the Ile52Ser mutation was confirmed by mutagenesis and by BCR studies. Structural modeling suggests that substitution of a small amino acid at position 52 (or 52a facilitates the insertion of CDR-H2 Phe54 and CDR-H3-Tyr into adjacent pockets on the stem. These results support the concept that activation and expansion of a defined subset of IGHV1-69-encoded B cells to produce potent HV1-69-sBnAbs does not necessarily require a heavily diversified V-segment acquired through recycling/reentry into the germinal center; rather, the incorporation of distinctive amino acid substitutions by Phase 2 long-patch error-prone repair of AID-induced mutations or by random non-AID SHM events may be sufficient. We propose that these routes of B cell maturation should be further investigated and exploited as a pathway for HV1-69-sBnAb elicitation by vaccination.

  9. Modeling the role of electron attachment rates on column density ratios for CnH-/CnH (n=4,6,8) in dense molecular clouds

    CERN Document Server

    Gianturco, F A; Wester, R

    2016-01-01

    (abridged) The fairly recent detection of a variety of anions in the Interstellar Molecular Clouds have underlined the importance of realistically modeling the processes governing their abundance. To this aim, our earlier calculations for the radiative electron attachment (REA) rates for C4H-, C6H-, and C8H- are employed to generate the corresponding column density ratios of anion/neutral (A/N) relative abundances. The latter are then compared with those obtained from observational measurements. The calculations involved the time-dependent solutions of a large network of chemical processes over an extended time interval and included a series of runs in which the values of REA rates were repeatedly scaled. Macroscopic parameters for the clouds' modeling were also varied to cover a broad range of physical environments. It was found that, within the range and quality of the processes included in the present network,and selected from state-of-the-art astrophysical databases, the REA values required to match the o...

  10. Curcumin induced nanoscale CD44 molecular redistribution and antigen-antibody interaction on HepG2 cell surface

    Energy Technology Data Exchange (ETDEWEB)

    Wang Mu [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Ruan Yuxia [Department of Ophthalmology, The First Affiliated Hospital, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Xing Xiaobo; Chen Qian; Peng, Yuan [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China); Cai Jiye, E-mail: tjycai@jnu.edu.cn [Department of Chemistry, Jinan University, 601 Huangpu Road West, Tianhe District, Guangzhou 510632 (China)

    2011-07-04

    Graphical abstract: Highlights: > In this study, we investigate the changes of CD44 expression and distribution on HepG2 cells after curcumin treatment. > We find curcumin is able to change the morphology and ultrastructure of HepG2 cells. > Curcumin can reduce the expression of CD44 molecules and induce the nanoscale molecular redistribution on cell surface. > The binding force between CD44-modified AFM tip and the HepG2 cell surface decreases after curcumin-treatment. - Abstract: The cell surface glycoprotein CD44 was implicated in the progression, metastasis and apoptosis of certain human tumors. In this study, we used atomic force microscope (AFM) to monitor the effect of curcumin on human hepatocellular carcinoma (HepG2) cell surface nanoscale structure. High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with curcumin. The membrane average roughness increased (10.88 {+-} 4.62 nm to 129.70 {+-} 43.72 nm) and the expression of CD44 decreased (99.79 {+-} 0.16% to 75.14 {+-} 8.37%). Laser scanning confocal microscope (LSCM) imaging showed that CD44 molecules were located on the cell membrane. The florescence intensity in control group was weaker than that in curcumin treated cells. Most of the binding forces between CD44 antibodies and untreated HepG2 cell membrane were around 120-220 pN. After being incubated with curcumin, the major forces focused on 70-150 pN (10 {mu}M curcumin-treated) and 50-120 pN (20 {mu}M curcumin-treated). These results suggested that, as result of nanoscale molecular redistribution, changes of the cell surface were in response to external treatment of curcumin. The combination of AFM and LSCM could be a powerful method to detect the distribution of cell surface molecules and interactions between molecules and their ligands.

  11. Toward a Universal Method for Preparing Molecularly Imprinted Polymer Nanoparticles with Antibody-like Affinity for Proteins.

    Science.gov (United States)

    Xu, Jingjing; Ambrosini, Serena; Tamahkar, Emel; Rossi, Claire; Haupt, Karsten; Tse Sum Bui, Bernadette

    2016-01-11

    We describe a potentially universal, simple and cheap method to prepare water-compatible molecularly imprinted polymer nanoparticles (MIP-NPs) as synthetic antibodies against proteins. The strategy is based on a solid phase synthesis approach where glass beads (GBs) are functionalized with a metal chelate, acting as a general affinity ligand to attract surface-bound histidines present on proteins. This configuration enables an oriented immobilization of the proteins, upon which thermoresponsive MIP-NPs are synthesized. The GBs play the role of both a reactor and a separation column since, after synthesis, the MIP-NPs are released from the support by a simple temperature change, resulting in protein-free polymers. The resulting MIP-NPs are endowed with improved binding site homogeneity, since the binding sites have the same orientation. Moreover, they are stable (no aggregation) in a buffer solution for prolonged storage time and exhibit apparent dissociation constants in the nanomolar range, with little or no cross-reactivity toward other proteins. PMID:26644006

  12. Influence of molecular weight of DNA on the determination of anti-DNA antibodies in systemic lupus erythematosus (SLE) sera by radioimmunoassay

    Energy Technology Data Exchange (ETDEWEB)

    Geisert, M.; Heicke, B.; Metzmann, E.; Zahn, R.K.

    1975-04-01

    Using a radioimmunoassay (RIA) based on the Farr technique with radioactively labeled /sup 3/H-DNA for quantitative measurements of anti-DNA antibodies in sera of patients with systemic lupus erythematosus (SLE), the influence of molecular weight of DNA (ranging from 0.1 x 10/sup 6/ to 22.0 x 10/sup 6/ daltons) on binding and precipitation in this system has been investigated. Comparing our results with mathematical models it follows that one antibody molecule is fixed on the average to a statistical DNA segment of 2 x 10/sup 6/ to 4 x 10/sup 6/ daltons. Furthermore binding capacity of the DNA was found to be independent of the molecular weight, as demonstrated in a double label experiment using /sup 14/C and /sup 3/H-labeled DNA of different size. However, the amount of radioactivity precipitated was found to depend on the molecular weight of the labeled DNA following a non-linear function. It was calculated that a minimal ratio of fixed antibody molecules per a certain size of DNA was necessary for precipitation. The mathematical treatment of the observed non-linear precipitation dependence will be discussed using various statistical models. The results indicate that the quantitative measurements of anti-DNA antibodies with the Farr technique e.g., for diagnosis and control of SLE in clinical immunology is highly dependent on the molecular weight of the labeled DNA used in the assay system and reliable results are only obtained with DNA of a sufficiently high molecular weight. (auth)

  13. Curcumin induced nanoscale CD44 molecular redistribution and antigen-antibody interaction on HepG2 cell surface

    International Nuclear Information System (INIS)

    Graphical abstract: Highlights: → In this study, we investigate the changes of CD44 expression and distribution on HepG2 cells after curcumin treatment. → We find curcumin is able to change the morphology and ultrastructure of HepG2 cells. → Curcumin can reduce the expression of CD44 molecules and induce the nanoscale molecular redistribution on cell surface. → The binding force between CD44-modified AFM tip and the HepG2 cell surface decreases after curcumin-treatment. - Abstract: The cell surface glycoprotein CD44 was implicated in the progression, metastasis and apoptosis of certain human tumors. In this study, we used atomic force microscope (AFM) to monitor the effect of curcumin on human hepatocellular carcinoma (HepG2) cell surface nanoscale structure. High-resolution imaging revealed that cell morphology and ultrastructure changed a lot after being treated with curcumin. The membrane average roughness increased (10.88 ± 4.62 nm to 129.70 ± 43.72 nm) and the expression of CD44 decreased (99.79 ± 0.16% to 75.14 ± 8.37%). Laser scanning confocal microscope (LSCM) imaging showed that CD44 molecules were located on the cell membrane. The florescence intensity in control group was weaker than that in curcumin treated cells. Most of the binding forces between CD44 antibodies and untreated HepG2 cell membrane were around 120-220 pN. After being incubated with curcumin, the major forces focused on 70-150 pN (10 μM curcumin-treated) and 50-120 pN (20 μM curcumin-treated). These results suggested that, as result of nanoscale molecular redistribution, changes of the cell surface were in response to external treatment of curcumin. The combination of AFM and LSCM could be a powerful method to detect the distribution of cell surface molecules and interactions between molecules and their ligands.

  14. Production of a monoclonal antibody specific for high molecular weight glutenin subunits (HMW-GS) in wheat and its antigenic determinant

    Institute of Scientific and Technical Information of China (English)

    WANG Hanqian; ZHANG Xueyong; WANG Hongmei; PANG Binshuang

    2005-01-01

    Wheat high molecular weight glutenin subunits (HMW-GS) 1Bx14 and 1By15 isolated by preparative SDS-PAGE are used as antigen to immunize BALB/c mice. Subcutaneous inoculation of the antigen is performed. The intra-peritoneal injection is completed 3 days before fusion with myeloma cell (SP2/0) via PEG-1500. The fusion cells are selected by indirect enzyme-linked immuno-sorbent assay (ELISA). Positive hybrid cells are further verified three times by limit dilution of the culture cells. A hybridoma cell line is successfully obtained. The monoclonal antibody belongs to IgG1 subclass. In immunoblotting, the antibody binds to all HMW-GS of T.aestivum cultivars, but does not bind to other storage proteins in seeds of wheat. This result is consisting with the high homology in amino acid sequences among the HMW glutenin subunits in wheat. The antibody also binds to HMW-GS storage proteins in Aegilops squarrosa and T. durum (durum wheat). Furthermore, it also binds to HMW storage proteins in Secale cereale (rye),Hordeum vulgare (barley). However, it never binds seed storage proteins in other cereals such as maize, oat, rice, foxtail millet, sorghum etc. The antigen determinant recognized by the antibody has been located within hexapeptide [PGQGQQ] or / and nonapeptide [GYYPTSPQQ] in the central repetitive region of HMW-GS.

  15. Molecular Mimicry: Sensitization of Lewis Rats With Campylobacter jejuni Lipopolysaccharides Induces Formation of Antibody Toward GD3 Ganglioside

    OpenAIRE

    Usuki, Seigo; Thompson, Stuart A.; Rivner, Michael H.; Taguchi, Kyoji; Shibata, Keiko; Ariga, Toshio; Robert K Yu

    2006-01-01

    Recently we have reported cases of demyelinating inflammatory neuropathy showing elevated titers of anti-GD3 antibodies, which occurs rarely in Guillain-Barré syndrome. To examine the correlation between the anti-GD3 antibody titer and Campylobacter jejuni infection, we sensitized female Lewis rats with lipopolysaccharides (LPSs) from serotype HS19 of C. jejuni and examined changes in nerve conduction velocity and nerve conduction block (P/D ratio). After 16 weeks of sensitization, animals re...

  16. Effect of Low Molecular Weight Heparins (LMWHs on antiphospholipid Antibodies (aPL-mediated inhibition of endometrial angiogenesis.

    Directory of Open Access Journals (Sweden)

    Silvia D'Ippolito

    Full Text Available Antiphospholipid syndrome (APS is an autoimmune disorder characterized by vascular thrombosis and/or pregnancy morbidity in the presence of circulating antiphospholipid antibodies (aPL. Different pathogenic mechanisms for aPL-mediated pregnancy failure have been proposed. In particular a direct effect of aPL on both maternal and fetal side of the placental tissue has been reported, since their reactivity with β2-glycoprotein I (β2GPI makes them adhere to trophoblast and human endometrial endothelial cell (HEEC membranes. β2GPI can be recognized by aPL that, once bound, interfere with both trophoblast functions and with the HEEC differentiation.APS patients can be successfully treated with Low Molecular Weight Heparin (LMWH. Recent reports suggest that LMWH acts through mechanisms alternative to its well known anticoagulant effect, because of its ability to bind β2GPI. In our previous studies, we showed that LMWH is able to reduce the aPL binding to trophoblasts and restore cell invasiveness and differentiation. So far, however, no study has described its effects on endometrial angiogenesis.The aim of our research was to evaluate whether two LMWHs, tinzaparin and enoxaparin, have an effect on the aPL-inhibited endometrial angiogenesis. This prompted us to investigate: (i in vitro HEEC angiogenesis through a Matrigel assay; (ii VEGF secretion by ELISA; (iii matrix metalloproteinase-2 (MMP-2 activity by gelatin zymography; (iv Nuclear Factor-κB (NF-κB DNA binding activity by colorimetric assay; (v STAT-3 activation by a sandwich-ELISA kit. Furthermore, using an in vivo murine model we investigated the LMWHs effects on angiogenesis.We demonstrated that the addition of LMWHs prevents aPL-inhibited HEEC angiogenesis, both in vitro and in vivo, and is able to restore the aPL inhibited NF-κB and/or STAT-3 activity, the VEGF secretion and the MMPs activity.The demonstration of a beneficial role for LMWHs on the aPL-inhibited HEEC angiogenesis

  17. Thyroid Antibodies

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? Thyroid Antibodies Share this page: Was this page helpful? Also known as: Thyroid Autoantibodies; Antithyroid Antibodies; Antimicrosomal Antibody; Thyroid Microsomal Antibody; ...

  18. Paternal Attachment, Parenting Beliefs and Children's Attachment

    Science.gov (United States)

    Howard, Kimberly S.

    2010-01-01

    Relationships between fathers' romantic attachment style, parenting beliefs and father-child attachment security and dependence were examined in a diverse sample of 72 fathers of young children. Paternal romantic attachment style was coded based on fathers' endorsement of a particular style represented in the Hazan and Shaver Three-Category…

  19. Immunoglobulin G4: an odd antibody

    NARCIS (Netherlands)

    R.C. Aalberse; S.O. Stapel; J. Schuurman; T. Rispens

    2009-01-01

    Despite its well-known association with IgE-mediated allergy, IgG4 antibodies still have several poorly understood characteristics. IgG4 is a very dynamic antibody: the antibody is involved in a continuous process of half-molecules (i.e. a heavy and attached light-chain) exchange. This process, also

  20. Enhancement of Antibodies to the Human Immunodeficiency Virus Type 1 Envelope by Using the Molecular Adjuvant C3d

    OpenAIRE

    Green, Thomas D.; David C Montefiori; Ross, Ted M.

    2003-01-01

    DNA vaccines expressing the envelope (Env) protein of the human immunodeficiency virus have been relatively ineffective at generating high-titer, long-lasting, neutralizing antibodies in a variety of animal models. In this study, the murine and human homologues of the complement component, C3d, were used in a DNA vaccine to enhance the titers of antibody to Env. Initially, plasmids expressing a secreted form of Env (sgp120) fused to one, two, or three copies of the murine homologue of C3d (mC...

  1. Theory for strength and stability of an unusual "ligand-receptor" bond: a microtubule attached to a wall by molecular motor tethers

    CERN Document Server

    Ghanti, Dipanwita

    2016-01-01

    A microtubule (MT) is a tubular stiff filament formed by a hierarchical organization of tubulin proteins. We develop a stochastic kinetic model for studying the strength and stability of a pre-formed attachment of a MT with a rigid wall where the MT is tethered to the wall by a group of motor proteins. Such an attachment, formed by the specific interactions between the MT and the motors, is an analog of ligand-receptor bonds, the MT and the motors anchored on the wall being the counterparts of the ligand and receptors, respectively. However, unlike other ligands, the length of a MT can change with time because of its polymerization-depolymerization kinetics. The simple model developed here is motivated by the MTs linked to the cell cortex by dynein motors. We present the theory for both force-ramp and force-clamp conditions. In the force-ramp protocol we investigate the strength of the attachment by assuming imposition of a time-dependent external load tension that increases linearly with time till the attach...

  2. Catalysis on the coastline: theozyme, molecular dynamics, and free energy perturbation analysis of antibody 21D8 catalysis of the decarboxylation of 5-nitro-3-carboxybenzisoxazole.

    Science.gov (United States)

    Ujaque, Gregori; Tantillo, Dean J; Hu, Yunfeng; Houk, K N; Hotta, Kinya; Hilvert, Donald

    2003-01-15

    Antibody 21D8 catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. The hapten used was designed to induce an antibody binding site with anion binders for the carboxylate, plus a nonpolar environment to accelerate decarboxylation. A recent X-ray crystal structure of 21D8 has shown that the binding pocket contains an array of both polar and charged residues. Nevertheless, 21D8 is able to catalyze a reaction that involves a decrease in polarity from reactant to transition state. The origins of this phenomenon were explored using various computational strategies-quantum mechanics, theozyme models, docking, molecular dynamics, free energy perturbation, and linear interaction energy-the combination of which has produced a consistent picture of catalysis. By partially desolvating the charged carboxylate, 21D8 manages to effect "catalysis on the coastline," without burying the carboxylate in a nonpolar region of the binding pocket. The results have implications for that broad class of enzyme and antibody catalyzed reactions that involve the conversion of a substrate with a relatively localized charge into a transition state with a highly dispersed charge.

  3. [Challenge to the Development of Molecular Targeted Therapy against a Novel Target Candidate Identified by Antibody Proteomics Technology].

    Science.gov (United States)

    Nagano, Kazuya

    2016-01-01

    Disease proteomics that systemically analyzes and identifies differentially expressed proteins between healthy and diseased samples is a potentially useful approach for obtaining target proteins for drug development. To date, however, very few target proteins have been identified from this field. A key issue that remains to be resolved is how to correctly identify target proteins from a number of potential candidates. To circumvent this problem, we have developed "antibody proteomics technology" in which a single chain Fv phage antibody library is utilized for proteome analysis. Here, we describe the application of this technology by primarily focusing on Eph receptor A10 (EphA10), a novel breast cancer-related protein that is a promising target for antibody drugs. To establish an effective and safe targeted cancer therapy, it is important that the target is specifically expressed in cancer tissues. Therefore, we attempted to analyze the EphA10 expression profiles. Tissue microarray analysis showed that EphA10 was expressed in all subtypes of breast cancer containing triple negative breast cancer cases. On the other hand, EphA10 was only expressed in testis tissue among 36 kinds of normal tissues. Thus, EphA10 could be a highly cancer-specific protein, making it a promising target for female breast cancer patients. Finally, we examined the anti-tumor effect by anti-EphA10 antibody, aiming for the development of a novel EphA10 targeting therapy. Administration of the antibody showed that tumor volumes were significantly inhibited. Our results suggest that targeting EphA10 in breast cancer cases might be a promising new form of therapy. PMID:26831784

  4. Adult Attachment and Psychotherapy

    OpenAIRE

    Rietzschel, Julia

    2012-01-01

    This thesis explores the association between adult attachment and psychological therapy by examining attachment as an outcome variable of therapy, as well as a predictor of therapy outcome. The literature review systematically explores research that has examined changes in attachment representations during psychological therapy. The purpose of the review is to enhance understanding of change processes in adult attachment and to provide empirical support to the premises of attachment theory. I...

  5. Attachment behavior in rats

    OpenAIRE

    Sigling, H.O.

    2009-01-01

    This thesis describes studies into the rat as an animal model for attachment, along the lines of Bowlby's attachment theory. First, the relation between attachment and human psychopathology is reviewed. The conclusion is that psychopathology is more frequent in insecure attached persons and that there is a relationship between specific types of insecure attachment and specific types of psychiatric disorders. Next, a reinterpretation of the literature on social preference experiments in rodent...

  6. Heavy chain only antibodies

    DEFF Research Database (Denmark)

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

    2013-01-01

    Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen-...... for combating HER2+ breast cancer. © 2013 by Tabriz University of Medical Sciences.......Unlike conventional antibodies, heavy chain only antibodies derived from camel contain a single variable domain (VHH) and two constant domains (CH2 and CH3). Cloned and isolated VHHs possess unique properties that enable them to excel conventional therapeutic antibodies and their smaller antigen......-binding fragments in cancer targeting and therapy. VHHs express low immunogenicity, are highly robust and easy to manufacture and have the ability to recognize hidden or uncommon epitopes. We highlight the utility of VHH in design of new molecular, multifunctional particulate and immune cell-based systems...

  7. Generation and molecular characterization of a monoclonal antibody reactive with conserved epitope in sphingomyelinases D from Loxosceles spider venoms.

    Science.gov (United States)

    Dias-Lopes, C; Felicori, L; Rubrecht, L; Cobo, S; Molina, L; Nguyen, C; Galéa, P; Granier, C; Molina, F; Chávez-Olortegui, C

    2014-04-11

    We report the production of a neutralizing monoclonal antibody able to recognize the venoms of three major medically important species of Loxosceles spiders in Brazil. The mAb was produced by immunization of mice with a toxic recombinant L. intermedia sphingomyelinase D {SMases D isoform (rLiD1)} [1] and screened by enzyme-linked immunosorbent assay (ELISA) using L. intermedia, L. laeta and L. gaucho venoms as antigens. One clone (LiD1mAb16) out of seventeen anti-rLiD1 hybridomas was cross-reactive with the three whole Loxosceles venoms. 2D Western blot analysis indicated that LiD1mAb16 was capable of interacting with 34 proteins of 29-36kDa in L. intermedia, 33 in L. gaucho and 27 in L. laeta venoms. The results of immunoassays with cellulose-bound peptides revealed that the LiD1mAb16 recognizes a highly conserved linear epitope localized in the catalytic region of SMases D toxins. The selected mAb displayed in vivo protective activity in rabbits after challenge with rLiD1. These results show the potential usefulness of monoclonal antibodies for future therapeutic approaches and also opens up the perspective of utilization of these antibodies for immunodiagnostic assays in loxoscelism.

  8. Preparation and binding study of a complex made of DNA-treated single-walled carbon nanotubes and antibody for specific delivery of a “molecular heater” platform

    Directory of Open Access Journals (Sweden)

    Kawaguchi M

    2012-08-01

    Full Text Available Minoru Kawaguchi,1,2 Jun Yamazaki,2,3 Jun Ohno,2,4 Tadao Fukushima2,51Department of Dental Engineering, Biomaterials Section, Fukuoka Dental College, Sawara-ku, Fukuoka; 2Japan Science and Technology Agency, Core Research of Evolutional Science and Technology, Chiyoda-ku, Tokyo; 3Department of Physiological Science and Molecular Biology, Section of Cellular and Molecular Regulation, 4Department of Morphological Biology, Pathology Section, 5Center for Regenerative Medicine, Fukuoka Dental College, Sawara-ku, Fukuoka, JapanAbstract: Carbon nanotubes have been explored as heat-delivery vehicles for thermal ablation of tumors. To use single-walled carbon nanotubes (SWNT as a “molecular heater” for hyperthermia therapy in cancer, stable dispersibility and smart-delivery potential will be needed, as well as lack of toxicity. This paper reports the preparation of a model complex comprising DNA-treated SWNT and anti-human IgG antibody and the specific binding ability of this model complex with the targeted protein, ie, human IgG. Treatment with double-stranded DNA enabled stable dispersibility of a complex composed of SWNT and the antibody under physiological conditions. Quartz crystal microbalance results suggest that there was one immobilized IgG molecule to every 21,700 carbon atoms in the complex containing DNA-treated SWNT and the antibody. The DNA-SWNT antibody complex showed good selectivity for binding to the targeted protein. Binding analysis revealed that treatment with DNA did not interfere with binding affinity or capacity between the immobilized antibody and the targeted protein. The results of this study demonstrate that the DNA-SWNT antibody complex is a useful tool for use as a smart “molecular heater” platform applicable to various types of antibodies targeting a specific antigen.Keywords: carbon nanotubes, DNA functionalization, complex, antibody, binding ability

  9. Adult attachment styles

    Directory of Open Access Journals (Sweden)

    Maša Žvelc

    2007-01-01

    Full Text Available Theory of attachment primarily described early relationships between a child and his caretakers. In the last twenty years there is a growing interest in adult attachment research. Theories and research findings of adult attachment stem from two different methodological approaches. The first approach measures adult attachment through Adult Attachment Interview (AAI; Main, 1991 where the attachment is assessed through the narratives of adult people of their early child experiences with their primary caretakers. The second approach measures adult attachment with the help of self-evaluative questionnaires, developed by (a Hazan and Shaver (1987 who started this approach in the field of personality and social psychology, and (b Bartholomew and Horowitz (1991. Research shows that there is significant correlation between early and adult attachment style. Attachment styles are passed from generation to generation. Basic adult attachment styles are: securely attached, preoccupied, fearful-avoidant, dismissing-avoidant and disorganized. Previous research using Barholomew and Horowitz (1991 Relationship Questionnaire on 176 Slovenian students showed that 48% students are securely attached, 29% are fearful-avoidant, 10% are dismissing-avoidant, and 13% have preoccupied attachment style. Theory of attachment is very useful for understanding the behavior and subjective experiences of children and adults. It is applicable to different contexts (psychotherapy, counseling, education .... The paper proposes further research focused on integration of adult attachment styles and types of object relations measured by Test of object relations (Žvelc, 1998 and Pictorial test of Separation and Individuation (Žvelc, 2003.

  10. A Molecular Model for Cocaine Binding by the Immunotherapeutic Human/Mouse Chimeric Monoclonal Antibody 2E2

    OpenAIRE

    Lape, Michael; Paula, Stefan; Ball, William J.

    2010-01-01

    Immunotherapy by cocaine-binding monoclonal antibodies (mAbs) has emerged as a promising strategy for the treatment of cocaine addiction. The human (γ1 heavy chain)/murine (λ light chain) chimeric mAb 2E2 has excellent affinity and specificity for cocaine and recent animal studies have demonstrated 2E2’s ability in vivo to reduce cocaine levels in the brain as well as alter cocaine self-administration behavior in rats. In this study, we used mAb 2E2 amino acid sequence information to create a...

  11. Attachment of cells to basement membrane collagen type IV

    OpenAIRE

    1986-01-01

    Of ten different cell lines examined, three showed distinct attachment and spreading on collagen IV substrates, and neither attachment nor spreading was enhanced by adding soluble laminin or fibronectin. This reaction was not inhibited by cycloheximide or antibodies to laminin, indicating a direct attachment to collagen IV without the need of mediator proteins. Cell-binding sites were localized to the major triple-helical domain of collagen IV and required an intact triple helical conformatio...

  12. Crystallization and molecular-replacement studies of the monoclonal antibody mAbR310 specific for the (R)-HNE-modified protein

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Sohei, E-mail: itosohei@u-shizuoka-ken.ac.jp [Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka 422-8526 (Japan); Tatsuda, Emi [Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601 (Japan); Ishino, Kousuke; Suzuki, Kenichiro; Sakai, Hiroshi [Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka 422-8526 (Japan); Uchida, Koji [Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601 (Japan); Department of Food and Nutritional Sciences, Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-Ku, Shizuoka 422-8526 (Japan)

    2006-06-01

    Antigen-free Fab fragment of mAbR310, which recognizes (R)-HNE modified protein, has been crystallized. Initial phases have been obtained by molecular replacement. 4-Hydroxy-2-nonenal (HNE), a major racemic product of lipid peroxidation, reacts with histidine to form a stable HNE–histidine Michael addition-type adduct possessing three chiral centres in the cyclic hemiacetal structure. Monoclonal antibodies against HNE-modified protein have been widely used for assessing oxidative stress in vitro and in vivo. Here, the purification, crystallization and preliminary crystallographic analysis of a Fab fragment of novel monoclonal antibody R310 (mAbR310), which recognizes (R)-HNE-modified protein, are reported. The Fab fragment of mAbR310 was obtained by digestion with papain, purified and crystallized. Using hanging-drop vapour-diffusion crystallization techniques, crystals of mAbR310 Fab were obtained. The crystal belongs to the monoclinic space group C2 (unit-cell parameters a = 127.04, b = 65.31, c = 64.29 Å, β = 118.88°) and diffracted X-rays to a resolution of 1.84 Å. The asymmetric unit contains one molecule of mAbR310, with a corresponding crystal volume per protein weight of 2.51 Å{sup 3} Da{sup −1} and a solvent content of 51.0%.

  13. Antibody profile of pregnant women with antiphospholipid syndrome and pregnancy outcome after treatment with low dose aspirin and low-weight-molecular heparin.

    Science.gov (United States)

    Glasnović, Marija; Bosnjak, Ivica; Vcev, Aleksandar; Soldo, Ivan; Kosuta, Maja; Lenz, Bahrija; Glasnović-Horvatić, Elizabeta; Soldo-Butković, Silva; Mićunović, Nikola

    2007-03-01

    The aim of the research was to show our diagnostic and therapeutic experience with antiphospholipid syndrome (APS) in pregnant women. 36 pregnant women suspect on APS were included in the study: 32 with primary antiphospholipd syndrome (PAPS) and 4 with secondary antiphospholipid syndrome (SAPS). All pregnant women received low-molecular-weight-heparin (LMWH) and low dose aspirin (LDA) therapy. Control group represented 26 women with SAPS and previous bad reproductive anamnesis. Average pregnancy lasted 37.06 +/- 0.707 weeks. LMWH and LDA therapy was successful in 97.22%. Lupus anticoagulant (LA) was found to be more frequent in PAPS group (71.87%). Anticardiolipin antibodies (aCL) were found to be more frequent in SAPS (26.66%). For three patients (3.37%), PAPS was diagnosed due to a fact that they had positive antibeta2-glycoproteinl (antibeta-GP1). To make APS diagnosis, it is of great importance to search for all antiphospholipid antibodies. LMWH and low dose of acetylsalicylic acid should be the first choice therapy.

  14. Belt attachment and system

    Science.gov (United States)

    Schneider, Abraham D.; Davidson, Erick M.

    2016-02-02

    Disclosed herein is a belt assembly including a flexible belt with an improved belt attachment. The belt attachment includes two crossbars spaced along the length of the belt. The crossbars retain bearings that allow predetermined movement in six degrees of freedom. The crossbars are connected by a rigid body that attaches to the bearings. Implements that are attached to the rigid body are simply supported but restrained in pitching rotation.

  15. Attachment Without Fear

    OpenAIRE

    Bell, David C.

    2009-01-01

    John Bowlby hypothesized an attachment system that interacts with caregiving, exploration, and fear systems in the brain, with a particular emphasis on fear. Neurobiological research confirms many of his hypotheses and also raises some new questions. A psychological model based on this neurobiological research is presented here. The model extends conventional attachment theory by describing additional attachment processes independent of fear. In this model, the attachment elements of trust, o...

  16. Special Attachments. Module 19.

    Science.gov (United States)

    South Carolina State Dept. of Education, Columbia. Office of Vocational Education.

    This module on special attachments, one in a series dealing with industrial sewing machines, their attachments, and operation, covers four topics: gauges; cording attachment; zipper foot; and hemming, shirring, and binding. For each topic these components are provided: an introduction, directions, an objective, learning activities, student…

  17. Precision Attachment: Retained Overdenture

    OpenAIRE

    Jayasree, K; Mrs.M.Bharathi; Nag, V. Dileep; B. Vinod

    2011-01-01

    Precision attachments are small interlocking devices to connect prosthesis and abutments that offer a variety of solutions to the challenge of balance between functional stability and cosmetic appeal. Precision attachments have wide applications, used in fixed removable bridge, removable partial dentures, overdentures, implant retained overdentures, and maxillofacial prosthesis. Attachment retained overdentures helps in distribution of masticatory forces, minimizes trauma to abutments and sof...

  18. Attachment and Psychopathology

    Directory of Open Access Journals (Sweden)

    Mehmet Fatih Ustundag

    2011-06-01

    Full Text Available The type of attachment defined in the early stages of life and thought to be continuous, is a phenomenon that shapes the pattern of how a person makes contact with others. The clinical appearance of every type of attachment is different and each one has prospective and retrospective phenomenological reflections. In all stages of life and in close relationships, it can be observed if a person gets in close contact with someone else and if this relation bears supportive and protective qualities. According to attachment theorists, once it is defined as safe or unsafe during nursing period, it shows little change. Starting from Bowlby’s work, unsafe attachment type is considered as the determining factor of psychopathology in the later periods of life, while safe attachment is considered as in relation with healthy processes. The nature’s original model is safe attachment. Anxious/indecisive attachment, an unsafe attachment type, is associated with anxiety disorders and depressive disorder, while avoidant attachment is associated with behavior disorder and other extroverted pathologies. Disorganized/disoriented attachment is considered to be together with dissociative disorder. The aim of this paper is to review attachment theory and the relation between attachment and psychopathology.

  19. Evaluation of the therapeutic efficacy of a VEGFR2-blocking antibody using sodium-iodide symporter molecular imaging in a tumor xenograft model

    Energy Technology Data Exchange (ETDEWEB)

    Cheong, Su-Jin; Lee, Chang-Moon; Kim, Eun-Mi [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Uhm, Tai-Boong [Faculty of Biological Science, Chonbuk National University, Jeonju-si, jeonbuk 561-756 (Korea, Republic of); Jeong, Hwan-Jeong, E-mail: jayjeong@chonbuk.ac.k [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Kim, Dong Wook; Lim, Seok Tae; Sohn, Myung-Hee [Department of Nuclear Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of); Cyclotron Research Center, Chonbuk National University Hospital, Jeonju-si, Jeonbuk 561-712 (Korea, Republic of)

    2011-01-15

    Purpose: Vascular endothelial growth factor receptor 2-blocking antibody (DC101) has inhibitory effects on tumor growth and angiogenesis in vivo. The human sodium/iodide symporter (hNIS) gene has been shown to be a useful molecular imaging reporter gene. Here, we investigated the evaluation of therapeutic efficacy by molecular imaging in reporter gene transfected tumor xenografts using a gamma imaging system. Methods: The hNIS gene was transfected into MDA-MB-231 cells using Lipofectamine. The correlation between the number of MDA-MB-231-hNIS cells and the uptake of {sup 99m}Tc-pertechnetate or {sup 125}I was investigated in vitro by gamma imaging and counting. MDA-MB-231-hNIS cells were injected subcutaneously into mice. When the tumor volume reached 180-200 mm{sup 3}, we randomly assigned five animals to each of three groups representing different tumor therapies; no DC101 (control), 100 {mu}g, or 150 {mu}g DC101/mouse. One week and 2 weeks after the first injection of DC101, gamma imaging was performed. Mice were sacrificed 2 weeks after the first injection of DC101. The tumor tissues were used for reverse transcriptase-polymerase chain reaction (RT-PCR) and CD31 staining. Results: Uptake of {sup 125}I and {sup 99m}Tc-pertechnetate into MDA-MB-231-hNIS cells in vitro showed correlation with the number of cells. In DC101 treatment groups, the mean tumor volume was smaller than that of the control mice. Furthermore, tumor uptake of {sup 125}I was lower than in the controls. The CD31 staining and RT-PCR assay results showed that vessel formation and expression of the hNIS gene were significantly reduced in the tumor tissues of treatment groups. Conclusion: This study demonstrated the power of molecular imaging using a gamma imaging system for evaluating the therapeutic efficacy of an antitumor treatment. Molecular imaging systems may be useful in evaluation and development of effective diagnostic and/or therapeutic antibodies for specific target molecules.

  20. Multi-determinants analysis of molecular alterations for predicting clinical benefit to EGFR-targeted monoclonal antibodies in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Andrea Sartore-Bianchi

    Full Text Available BACKGROUND: KRAS mutations occur in 35-45% of metastatic colorectal cancers (mCRC and preclude responsiveness to EGFR-targeted therapy with cetuximab or panitumumab. However, less than 20% patients displaying wild-type KRAS tumors achieve objective response. Alterations in other effectors downstream of the EGFR, such as BRAF, and deregulation of the PIK3CA/PTEN pathway have independently been found to give rise to resistance. We present a comprehensive analysis of KRAS, BRAF, PIK3CA mutations, and PTEN expression in mCRC patients treated with cetuximab or panitumumab, with the aim of clarifying the relative contribution of these molecular alterations to resistance. METHODOLOGY/PRINCIPAL FINDINGS: We retrospectively analyzed objective tumor response, progression-free (PFS and overall survival (OS together with the mutational status of KRAS, BRAF, PIK3CA and expression of PTEN in 132 tumors from cetuximab or panitumumab treated mCRC patients. Among the 106 non-responsive patients, 74 (70% had tumors with at least one molecular alteration in the four markers. The probability of response was 51% (22/43 among patients with no alterations, 4% (2/47 among patients with 1 alteration, and 0% (0/24 for patients with > or =2 alterations (p or =2 molecular alteration(s (p<0.001. CONCLUSIONS/SIGNIFICANCE: When expression of PTEN and mutations of KRAS, BRAF and PIK3CA are concomitantly ascertained, up to 70% of mCRC patients unlikely to respond to anti-EGFR therapies can be identified. We propose to define as 'quadruple negative', the CRCs lacking alterations in KRAS, BRAF, PTEN and PIK3CA. Comprehensive molecular dissection of the EGFR signaling pathways should be considered to select mCRC patients for cetuximab- or panitumumab-based therapies.

  1. Positron-attachment to small molecules: Vibrational enhancement of positron affinities with configuration interaction level of multi-component molecular orbital approach

    Energy Technology Data Exchange (ETDEWEB)

    Tachikawa, Masanori [Quantum Chemistry Division, Graduate School of NanoBioScience, Yokohama City University, 22-2 Seto, Kanazawa, Yokohama 236-0027 (Japan)

    2015-12-31

    To theoretically demonstrate the binding of a positron to small polarized molecules, we have calculated the vibrational averaged positron affinity (PA) values along the local vibrational contribution with the configuration interaction level of multi-component molecular orbital method. This method can take the electron-positron correlation contribution into account through single electronic - single positronic excitation configurations. The PA values are enhanced by including the local vibrational contribution from vertical PA values due to the anharmonicity of the potential.

  2. Monoclonal antibodies with equal specificity to D-dimer and high-molecular-weight fibrin degradation products

    Science.gov (United States)

    Kogan, Alexander E.; Mukharyamova, Kadriya S.; Bereznikova, Anastasia V.; Filatov, Vladimir L.; Koshkina, Ekaterina V.; Bloshchitsyna, Marina N.; Katrukha, Alexey G.

    2016-01-01

    Fibrin degradation results in the formation of fibrin degradation products (FDPs) of different molecular weights, which include D-dimer. Commercial D-dimer assays recognize multiple forms of FDP with different specificity. As a result, the absence of an international D-dimer standard and the marked discrepancy in the D-dimer values in the same samples measured by assays from different manufacturers have become the primary problems that clinicians face in the D-dimer determination. We consider that an assay with equal specificity to all FDP forms regardless of their molecular weights could help to solve these problems. We aimed to produce mAbs that could equally recognize high-molecular-weight FDP (HMW FDP) and D-dimer. mAbs against D-dimer were produced. The HMW FDP/D-dimer ratios in plasma samples were analyzed following protein separation by gel filtration using the developed fluoroimmunoassay. A sandwich immunoassay with equal specificity to HMW FDP and D-dimer was developed and applied to determine HMW FDP/D-dimer ratios in patients with different diseases. Although the HMW FDP levels prevailed in thrombotic patients, the FDP and D-dimer levels were comparable in septic patients. Meanwhile, the D-dimer levels often exceeded the HMW FDP levels in patients who had undergone surgery. The ‘D-dimer’ levels that were detected by different assays also varied greatly depending on the assay specificities to FDP and D-dimer. Our findings show that the introduction of assays with equal specificities to FDP and D-dimer in clinical practice is a possible way of standardizing D-dimer measurements. PMID:26656897

  3. Blade attachment assembly

    Science.gov (United States)

    Garcia-Crespo, Andres Jose; Delvaux, John McConnell; Miller, Diane Patricia

    2016-05-03

    An assembly and method for affixing a turbomachine rotor blade to a rotor wheel are disclosed. In an embodiment, an adaptor member is provided disposed between the blade and the rotor wheel, the adaptor member including an adaptor attachment slot that is complementary to the blade attachment member, and an adaptor attachment member that is complementary to the rotor wheel attachment slot. A coverplate is provided, having a coverplate attachment member that is complementary to the rotor wheel attachment slot, and a hook for engaging the adaptor member. When assembled, the coverplate member matingly engages with the adaptor member, and retains the blade in the adaptor member, and the assembly in the rotor wheel.

  4. Specificity of mimotope-induced anti-high molecular weight-melanoma associated antigen (HMW-MAA antibodies does not ensure biological activity.

    Directory of Open Access Journals (Sweden)

    Julia Latzka

    Full Text Available Vaccines based on peptide mimics (mimotopes of conformational tumor antigen epitopes have been investigated for a variety of human tumors including breast cancer, tumors expressing the carcinoembryonic antigen, B cell lymphoma, neuroblastoma, and melanoma. In our previous work, we designed a vaccine based on a mimotope of the high molecular weight-melanoma associated antigen (HMW-MAA that elicited HMW-MAA-specific antibodies (Abs with anti-tumor activity in vitro and in vivo. In this study, we aimed to identify mimotopes of additional distinct HMW-MAA epitopes, since they could be used to construct a polymimotope melanoma vaccine. For this purpose, random peptide phage libraries were screened with the anti-HMW-MAA monoclonal antibodies (mAbs VT80.12 and VF1-TP43 yielding one peptide ligand for each mAb. Both peptides inhibited the binding of the corresponding mAb to the HMW-MAA. Furthermore, when coupled to the carrier protein keyhole limpet hemocyanin (KLH, both HMW-MAA mimotopes elicited peptide-specific Abs in rabbits or BALB/c mice, but only the mimotope isolated with the mAb VT80.12 elicited HMW-MAA-specific Abs and only in mice. However, the latter Abs had no detectable effect on HMW-MAA expressing human melanoma cells in vitro. These results describe limitations related to the phage display technique and emphasize the need to characterize the functional properties of the mAb utilized to isolate mimotopes of the corresponding epitopes.

  5. Temperament and Attachment Disorders

    Science.gov (United States)

    Zeanah, Charles H.; Fox, Nathan A.

    2004-01-01

    Reviewed in this article is research on children with reactive attachment disorder (RAD) who exhibit specific patterns of socially aberrant behavior resulting from being maltreated or having limited opportunities to form selective attachments. There are no data explaining why 2 different patterns of the disorder, an emotionally withdrawn-inhibited…

  6. Attachment and Early Maltreatment.

    Science.gov (United States)

    Egeland, Byron; Sroufe, L. Alan

    1981-01-01

    Attachment outcomes of 31 maltreatment cases (involving extreme neglect or abuse), selected from a total poverty sample of 267 high-risk mothers and their children, were compared to those of a subsample of 33 cases with a history of excellent care. Attachment was assessed when infants were 12 and 18 months old. (Author/MP)

  7. Attachment Security and Pain

    DEFF Research Database (Denmark)

    Andersen, Tonny Elmose; Lahav, Yael; Defrin, Ruth;

    2015-01-01

    The present study assesses for the first time, the possible disruption effect of posttraumatic stress symptoms (PTSS) with regard to the protective role of attachment on pain, among ex-POWs. While secure attachment seems to serve as a buffer, decreasing the perception of pain, this function may...

  8. Adolescent attachment and psychopathology.

    Science.gov (United States)

    Rosenstein, D S; Horowitz, H A

    1996-04-01

    The relationships among attachment classification, psychopathology, and personality traits were examined in a group of 60 psychiatrically hospitalized adolescents. The concordance of attachment classification was examined in 27 adolescent-mother pairs. Both adolescent and maternal attachment status were overwhelmingly insecure and were highly concordant. Adolescents showing a dismissing attachment organization were more likely to have a conduct or substance abuse disorder, narcissistic or antisocial personality disorder, and self-reported narcissistic, antisocial, and paranoid personality traits. Adolescents showing a preoccupied attachment organization were more likely to have an affective disorder, obsessive-compulsive, histrionic, borderline or schizotypal personality disorder, and self-reported avoidant, anxious, and dysthymic personality traits. The results support a model of development of psychopathology based partially on relational experiences with parents.

  9. Attachment-related psychodynamics.

    Science.gov (United States)

    Shaver, Phillip R; Mikulincer, Mario

    2002-09-01

    Because there has been relatively little communication and cross-fertilization between the two major lines of research on adult attachment, one based on coded narrative assessments of defensive processes, the other on simple self-reports of 'attachment style' in close relationships, we here explain and review recent work based on a combination of self-report and other kinds of method, including behavioral observations and unconscious priming techniques. The review indicates that considerable progress has been made in testing central hypotheses derived from attachment theory and in exploring unconscious, psychodynamic processes related to affect-regulation and attachment-system activation. The combination of self-report assessment of attachment style and experimental manipulation of other theoretically pertinent variables allows researchers to test causal hypotheses. We present a model of normative and individual-difference processes related to attachment and identify areas in which further research is needed and likely to be successful. One long-range goal is to create a more complete theory of personality built on attachment theory and other object relations theories.

  10. Environmental and genetic influences on early attachment.

    Science.gov (United States)

    Gervai, Judit

    2009-01-01

    Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief. PMID:19732441

  11. Environmental and genetic influences on early attachment

    Directory of Open Access Journals (Sweden)

    Gervai Judit

    2009-09-01

    Full Text Available Abstract Attachment theory predicts and subsequent empirical research has amply demonstrated that individual variations in patterns of early attachment behaviour are primarily influenced by differences in sensitive responsiveness of caregivers. However, meta-analyses have shown that parenting behaviour accounts for about one third of the variance in attachment security or disorganisation. The exclusively environmental explanation has been challenged by results demonstrating some, albeit inconclusive, evidence of the effect of infant temperament. In this paper, after reviewing briefly the well-demonstrated familial and wider environmental influences, the evidence is reviewed for genetic and gene-environment interaction effects on developing early attachment relationships. Studies investigating the interaction of genes of monoamine neurotransmission with parenting environment in the course of early relationship development suggest that children's differential susceptibility to the rearing environment depends partly on genetic differences. In addition to the overview of environmental and genetic contributions to infant attachment, and especially to disorganised attachment relevant to mental health issues, the few existing studies of gene-attachment interaction effects on development of childhood behavioural problems are also reviewed. A short account of the most important methodological problems to be overcome in molecular genetic studies of psychological and psychiatric phenotypes is also given. Finally, animal research focusing on brain-structural aspects related to early care and the new, conceptually important direction of studying environmental programming of early development through epigenetic modification of gene functioning is examined in brief.

  12. The Possible Role of Transplacentally-Acquired Antibodies to Infectious Agents, With Molecular Mimicry to Nervous System Sialic Acid Epitopes, as Causes of Neuromental Disorders: Prevention and Vaccine Implications

    Directory of Open Access Journals (Sweden)

    André J. Nahmias

    2006-01-01

    Full Text Available Proof of causality of most neuromental disorders (NMD's is largely unavailable. Lessons from four-decade investigations of the epidemiology, immunology, pathogenesis, prevention and therapy of perinatal infectious agents, which invade directly the nervous system, have led us to propose a new indirect effect hypothesis: maternal transplacentally-acquired antibodies, to agents with epitope molecular mimicry with the developing nervous system, can cross the fetus/infant's blood–nervous system barriers to cause NMD's, clinically manifest years later.

  13. Attachment and Psychotherapy

    OpenAIRE

    McKay, J.M.

    2010-01-01

    The aim of this study was to explore the relationship between therapy outcome, the therapeutic alliance and both patient and therapist attachment styles. 14 therapists and 27 patients participated. 78.57% (n = 11) therapists and 29.63% (n = 8) patients were classified as securely attached by self-report measures. It was predicted that more patients of secure therapists would show clinically significant improvement as determined by CORE-OM scores. However, 21.05% of patients with a secure atta...

  14. Attachment and coercive sexual behavior.

    Science.gov (United States)

    Smallbone, S W; Dadds, M R

    2000-01-01

    This study examined the relationships between childhood attachment and coercive sexual behavior. One hundred sixty-two male undergraduate students completed self-report measures of childhood maternal attachment, childhood paternal attachment, adult attachment, antisociality, aggression, and coercive sexual behavior. As predicted, insecure childhood attachment, especially insecure paternal attachment, was associated with antisociality, aggression, and coercive sexual behavior. Moreover, childhood attachment independently predicted coercive sexual behavior after antisociality and aggression were statistically controlled. The hypothesis that paternal avoidant attachment would predict coercive sexual behavior independently of its relationship with aggression and antisociality was also supported. Posthoc analysis indicated that maternal anxious attachment was associated with antisociality and that paternal avoidant attachment was associated with both antisociality and coercive sexual behavior. These results are consistent with criminological and psychological research linking adverse early family experiences with offending and lend support to an attachment-theoretical framework for understanding offending behavior in general and sexual offending behavior in particular.

  15. Antibody binding to p-Si using LANL SAM chemistry

    Energy Technology Data Exchange (ETDEWEB)

    Anderson, Aaron S [Los Alamos National Laboratory

    2010-12-06

    This NMSBA-sponsored project involves the attachment of antibodies to polymeric silicon (p-Si) surfaces, with the ultimate goal of attaching antibodies to nanowires for Vista Therapeutics, Inc. (Santa Fe, NM). This presentation describes the functionalization of p-Si surfaces. the activation of terminal carboxylates on these surfaces, the conjugation of antibodies, and the analyses undertaken at each step. The results of this work show that antibody conjugation is possible on p-Si coatings using the well-known EDC/NHS activation chemistry.

  16. Ladder attachment platform

    Science.gov (United States)

    Swygert,; Richard, W [Springfield, SC

    2012-08-28

    A ladder attachment platform is provided that includes a base for attachment to a ladder that has first and second side rails and a plurality of rungs that extend between in a lateral direction. Also included is a user platform for having a user stand thereon that is carried by the base. The user platform may be positioned with respect to the ladder so that it is not located between a first plane that extends through the first side rail and is perpendicular to the lateral direction and a second plane that extends through the second side rail and is perpendicular to the lateral direction.

  17. Development of a monoclonal antibody-based broad-specificity ELISA for fluroquinolone antibiotics in foods and molecular modeling studies of cross-reactive compounds

    Science.gov (United States)

    Development of a competitive indirect enzyme-linked immunosorbent assay (ciELISA) with monoclonal antibodies (Mabs) having broad specificity for fluoroquinolone (FQ) antibiotics is described. Four FQs, ciprofloxacin (CIP), norfloxacin (NOR), enrofloxacin (ENR) and ofloxacin (OFL) were conjugated to...

  18. Studies towards the understanding of the effects of ionizing radiations at the molecular scale (20-150 keV H{sup +}/H + He Collisions; dissociative electron attachment to water)

    Energy Technology Data Exchange (ETDEWEB)

    Coupier, B

    2005-11-15

    This work comes within the scope of recent studies towards a better understanding of the effect of ionizing radiation at the molecular scale on biological systems. It is composed of two parts. The first one presents a new set of coincidence measurements of cross sections for the impact of protons or hydrogen atoms on helium in the energy range 20-150 keV of interest for the radiation biology. It is an archetypical system of interest for the theoreticians and there exists only a few studies on the impact of hydrogen atoms on helium. This study with helium was also motivated for the sake of performing a general test of functioning of the apparatus before investigating more complicated systems. Similar studies were then performed by replacing helium with water and biological molecules of relevance (Uracil, Thymine...) as target. This constitutes a study of direct effects of fast ionizing radiations on molecules of biological interest. The second part of the thesis deals with another type of ionizing radiations which can be seen as indirect effects of the first fast ionizing radiations studied in the first part. Low energy electrons emission in the energy range 1 to 16 eV follows the bombardment of the matter by swift protons/hydrogen atoms; these electrons have in turn an ionizing influence on the environment. A review of the dissociative electron attachment to water was undertaken motivated by the existing discrepancies between old studies on the same subject. A special attention was given to the problem of high energy kinetic ion discrimination in the trochoidal monochromator used for this work. (author)

  19. MOWER ATTACHMENT NOISE

    OpenAIRE

    Mosdzianowski, G.

    1990-01-01

    The noise produced by grass mowing attachments fitted to small tractors and combining a number of rotary blades with a total cutting width of up to 120 cm was investigated. The paper develops a noise reduction concept based on an analysis of sound sources.

  20. Attachment and Personality Disorders

    Science.gov (United States)

    Sinha, Preeti; Sharan, Pratap

    2007-01-01

    Personality disorders (PDs) arise from core psychopathology of interpersonal relationships and understanding of self and others. The distorted representations of self and others, as well as unhealthy relationships that characterize persons with various PDs, indicate the possibility that persons with PDs have insecure attachment. Insecure…

  1. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Miyamura, Tatsuo; Saito, Izumu (National Institute of Health, Tokyo (Japan)); Katayama, Tohru (Tokyo National Chest Hospital (Japan)); Kikuchi, Shu; Tateda, Akira (Sendai National Hospital (Japan)); Houghton, M.; Choo, Quilim; Kuo, G. (Chiron Corporation, Emeryville, CA (USA))

    1990-02-01

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented.

  2. Detection of antibody against antigen expressed by molecularly cloned hepatitis C virus cDNA: Application to diagnosis and blood screening for posttransfusion hepatitis

    International Nuclear Information System (INIS)

    A cDNA clone has been derived from the plasma of a chimpanzee with chronic non-A, non-B viral hepatits (NANBH). The authors have assayed for antibodies reacting with the encoded antigen in sera from posttransfusion hepatitis patients (643 samples from 23 patients) and their corresponding donors collected during the past 10 years in Japan. The antibody was detected in 15 out of 17 (88.2%) posttransfusion NANBH (PT-NANBH) patients whose sera over time displayed multiple alanine aminotransferase (ALT) peaks. In general, the antibody was detected after several peaks of serum ALT elevations and, once detected, it persisted for years. Of the 15 well-defined cases of PT-NANBH that showed multiple ALT peaks and hepatitis C virus seroconversions, 11 (73.3%) were shown to be transfused with at least one unit of blood positive for the antibody. The retrospective analysis showed that all tested donor blood found to be positive for the antibody had been transfused to recipients who afterwards developed NANBH. These data strongly suggest that the cloned cDNA originated from an etiological agent of NANBH termed the hepatitis C virus. Furthermore, the present study demonstrates that had the screening been done with the anti-hepatitis C virus assay, 11 out of 17 (64.7%) cases of chronic PT-NANBH and 1 out of 6 (16.6%) acute PT-NANBH would have been prevented

  3. Picturing Urban Green Attachments

    DEFF Research Database (Denmark)

    Blok, Anders; Meilvang, Marie Leth

    2015-01-01

    In this article, we explore the cultural-political tensions and ambiguities of urban ecology, by way of following how activists move and translate between ‘familiar’ and ‘public’ engagements in the green city. Empirically, we locate our exploration in and around Nordhavnen (The North Harbor...... in the plural’ in the city. In particular, we stress the role assumed in such engagements by various image-making practices, as means for activists to express, share and render publicly visible a range of embodied urban attachments. Pragmatic sociology, we conclude, may contribute to a novel understanding...... of urban politics as inclusive learning processes, more hospitable to a wider diversity of familiar attachments to cities and their ecologies....

  4. Turbine nozzle attachment system

    Science.gov (United States)

    Norton, Paul F.; Shaffer, James E.

    1995-01-01

    A nozzle guide vane assembly having a preestablished rate of thermal expansion is positioned in a gas turbine engine and being attached to conventional metallic components. The nozzle guide vane assembly includes a pair of legs extending radially outwardly from an outer shroud and a pair of mounting legs extending radially inwardly from an inner shroud. Each of the pair of legs and mounting legs have a pair of holes therein. A plurality of members attached to the gas turbine engine have a plurality of bores therein which axially align with corresponding ones of the pair of holes in the legs. A plurality of pins are positioned within the corresponding holes and bores radially positioning the nozzle guide vane assembly about a central axis of the gas turbine engine.

  5. Universally Rigid Framework Attachments

    CERN Document Server

    Ratmanski, Kiril

    2010-01-01

    A framework is a graph and a map from its vertices to R^d. A framework is called universally rigid if there is no other framework with the same graph and edge lengths in R^d' for any d'. A framework attachment is a framework constructed by joining two frameworks on a subset of vertices. We consider an attachment of two universally rigid frameworks that are in general position in R^d. We show that the number of vertices in the overlap between the two frameworks must be sufficiently large in order for the attachment to remain universally rigid. Furthermore, it is shown that universal rigidity of such frameworks is preserved even after removing certain edges. Given positive semidefinite stress matrices for each of the two initial frameworks, we analytically derive the PSD stress matrices for the combined and edge-reduced frameworks. One of the benefits of the results is that they provide a general method for generating new universally rigid frameworks.

  6. Attachment disorganization in different clinical groups: What underpins unresolved attachment?

    OpenAIRE

    Juen Florian; Arnold Lisa; Meissner Dominik; Nolte Tobias; Buchheim Anna

    2013-01-01

    This paper summarizes findings and clinical implications of research on attachment disorganization in diverse clinical groups. Disorganized/unresolved attachment is overrepresented in these groups compared to healthy control participants, but disorder specific characteristics of this attachment pattern are still poorly understood. The focus of this study was to explore defensive processes in participants whose narratives were classified as disorganized/unresolved using the Adult Attach...

  7. 'MYCOPLASMA PNEUMONIAE' INFECTION: ROLE OF A SURFACE PROTEIN IN THE ATTACHMENT ORGANELLE

    Science.gov (United States)

    Attachment of Mycoplasma pneumoniae to host cells by means of a specialized terminus initiates infection. Monoclonal antibodies to a surface protein (Pl) inhibit this process, and react with a region of the tip covered with peplomer-like particles. Since antibodies against the Pl...

  8. Antibody detection and molecular characterization of toxoplasma gondii from bobcats (Lynx rufus), domestic cats (Felis catus), and wildlife from Minnesota, USA

    Science.gov (United States)

    Little is known of the epidemiology of toxoplasmosis in Minnesota. In this study, we evaluated Toxoplasma gondii infection in 50 wild bobcats (Lynx rufus) and 75 other animals on/near 10 cattle farms. Antibodies to T. gondii were assayed in serum samples or tissue fluids by the modified agglutinatio...

  9. Attachment as an Organizational Construct

    Science.gov (United States)

    Sroufe, L. Alan; Waters, Everett

    1977-01-01

    Discusses the conflict between situational influences and stable individual differences in attachment behavior and attempts to resolve this conflict by examining the functions, outcomes, and context sensitivity of attachment behavior and the underlying behavioral control systems that organize it. (JMB)

  10. Attachment Behaviors in Autistic Children.

    Science.gov (United States)

    Sigman, Marian; Ungerer, Judy A.

    1984-01-01

    Observation of 14 autistic and 14 nonautistic children of equivalent mental age revealed that autistic Ss showed evidence of attachment to their mothers. Among autistic Ss, those showing increased attachment behaviors in response to separation and reunion demonstrated more advanced symbolic play skills than those showing no attachment change.…

  11. Attachment Theory: Retrospect and Prospect.

    Science.gov (United States)

    Bretherton, Inge

    1985-01-01

    Provides overview of attachment theory as parented by John Bowlby in "Attachment and Loss". Uses two major concepts from this work to interpret refinements and elaborations of attachment theory attibuted to Mary Ainsworth. Considers how recent insights into development of socioemotional understanding and development of event representation can be…

  12. Attachment Theory in Tourism

    Directory of Open Access Journals (Sweden)

    Maximiliano Korstanje

    2007-01-01

    Full Text Available The following work is intended to a revision on attachment theory. The postulates of the theory of the sure base point that the system of exploration meets in narrow relation the system of conducts of attachment and the figure of the keepers. The conducts that characterize and symbolize the relation of the adult with the environment are carried back to the early age, in the moment in which the child develops the affective capacity. What difference does exist between someone who decides to journey to England and that one that one decides to travel to Mar del Plata? How it is possible to study this topic of on a manner trustworthy? These three questions were key to begin the investigation. Nevertheless, the matter began to find certain limitations linked to the methodology that had to be in use. It is possible to use careless they on the leisure scope, a theory which still demonstrates certain inconsistencies in its own clinical application?

  13. Attachment is a dynamic system

    Directory of Open Access Journals (Sweden)

    Zlatka Cugmas

    2003-04-01

    Full Text Available On the basis of the study of recent scientific literature about the development of attachment, the author answers the following questions: which are the postulates the theory of attachment has about the stability of the patterns of attachment, which level of stability in the patterns of attachment from infancy to adulthood these studies illuminate and which factors significantly influence the (instability of the patterns of attachment in time. The theory of attachment assumes that normal circumstances elicit stability. Changes, however, can be the result of important events influencing the sensitivity of the object of attachment. Agreement has not yet been reached regarding the percentage of stability in the patterns of attachment. There is more agreement regarding attachment in adulthood than that in childhood. The results depend on the size and characteristics of the subjects of the research, the measuring instruments, type of data analysis etc. The author concludes that attachment is a dynamic system influenced by significant changes in life (the cognitive development of the child, external care, parents' divorce, different stressful situations. As the influence of stressful events on the individual person' s quality of attachment is examined, it is necessary to consider also his/her temperamental characteristics, role of other people in their lives, etc.

  14. Mapping and measuring place attachment

    DEFF Research Database (Denmark)

    Brown, Greg; Raymond, Christopher Mark; Corcoran, Jonathan

    2015-01-01

    ) identify how participant socio-demographic and home location attributes influence place attachment, (4) provide some guidance for mapping place attachment in future research. We found large spatial variability in individual place attachment and mapped landscape values using both area and distance......-based measures. The area of place attachment is influenced by occupational roles such as farming or conservation, as well as home location, especially in coastal versus non-coastal contexts. The spatial distribution of mapped landscape values or values home range is related to, but not identical to mapped place...... attachment with just over half of landscape values located outside the area of mapped place attachment. Economic livelihood values, as an indicator of place dependence, and social values, as an indicator of place identity, are more likely to be mapped within the place attachment area. Aggregated place...

  15. Site-specific antibody-liposome conjugation through copper-free click chemistry: a molecular biology approach for targeted photodynamic therapy (Conference Presentation)

    Science.gov (United States)

    Obaid, Girgis; Wang, Yucheng; Kuriakose, Jerrin; Broekgaarden, Mans; Alkhateeb, Ahmed; Bulin, Anne-Laure; Hui, James; Tsourkas, Andrew; Hasan, Tayyaba

    2016-03-01

    Nanocarriers, such as liposomes, have the ability to potentiate photodynamic therapy (PDT) treatment regimens by the encapsulation of high payloads of photosensitizers and enhance their passive delivery to tumors through the enhanced permeability and retention effect. By conjugating targeting moieties to the surface of the liposomal nanoconstructs, cellular selectivity is imparted on them and PDT-based therapies can be performed with significantly higher dose tolerances, as off-target toxicity is simultaneously reduced.1 However, the maximal benefits of conventional targeted nanocarriers, including liposomes, are hindered by practical limitations including chemical instability, non-selective conjugation chemistry, poor control over ligand orientation, and loss of ligand functionality following conjugation, amongst others.2 We have developed a robust, physically and chemically stable liposomal nanoplatform containing benzoporphyrin derivative photosensitizer molecules within the phospholipid bilayer and an optimized surface density of strained cyclooctyne moieties for `click' conjugation to azido-functionalized antibodies.3 The clinical chimeric anti-EGFR antibody Cetuximab is site-specifically photocrosslinked to a recombinant bioengineered that recognizes the antibody's Fc region, containing a terminal azide.4 The copper-free click conjugation of the bioengineered Cetuximab derivative to the optimized photosensitizing liposome provides exceptional control over the antibody's optimal orientation for cellular antigen binding. Importantly, the reaction occurs rapidly under physiological conditions, bioorthogonally (selectively in the presence of other biomolecules) and without the need for toxic copper catalysis.3 Such state-of-the-art conjugation strategies push the boundaries of targeted photodynamic therapy beyond the limitations of traditional chemical coupling techniques to produce more robust and effective targeted therapeutics with applications beyond

  16. Why Does the Molecular Structure of Broadly Neutralizing Monoclonal Antibodies Isolated from Individuals Infected with HIV-1 not Inform the Rational Design of an HIV-1 Vaccine?

    Directory of Open Access Journals (Sweden)

    Marc H V Van Regenmortel

    2015-05-01

    Full Text Available It is commonly assumed that neutralizing Mabs that bind to the HIV-1 Env glycoprotein are more specific reagents than anti-HIV-1 polyclonal antisera and that knowledge of the structure of these Mabs facilitates the rational design of effective HIV-1 vaccine immunogens. However, after more than ten years of unsuccessful experimentation using the structure-based reverse vaccinology approach, it is now evident that it is not possible to infer from the structure of neutralizing Mabs which HIV immunogens induced their formation nor which vaccine immunogens will elicit similar Abs in an immunized host. The use of Mabs for developing an HIV-1 vaccine was counterproductive because it overlooked the fact that the apparent specificity of a Mab very much depends on the selection procedure used to obtain it and also did not take into account that an antibody is never monospecific for a single epitope but is always polyspecific for many epitopes. When the rationale of the proponents of the unsuccessful rational design strategy is analyzed, it appears that investigators who claim they are designing a vaccine immunogen are only improving the binding reactivity of a single epitope-paratope pair and are not actually designing an immunogen able to generate protective antibodies. The task of a designer consists in imagining what type of immunogen is likely to elicit a protective immune response but in the absence of knowledge regarding which features of the immune system are responsible for producing a functional neutralizing activity in antibodies, it is not feasible to intentionally optimize a potential immunogen candidate in order to obtain the desired outcome. The only available option is actually to test possible solutions by trial-and-error experiments until the preset goal is perhaps attained. Rational design and empirical approaches in HIV vaccine research should thus not be opposed as alternative options since empirical testing is an integral part of a so

  17. Immunoenzymatic detection of three kinds of 43,000-molecular-weight antigens by monoclonal antibodies in the insoluble fraction of Toxoplasma gondii.

    OpenAIRE

    Ogata, K.; Kasahara, T; Shioiri-Nakano, K; Igarashi, I; Suzuki, M.

    1984-01-01

    Monoclonal antibodies (TpM 3, TpM 6, and TpM 19) against Toxoplasma gondii insoluble antigens were produced by the hybridization of NS-1, a mouse myeloma cell line, with spleen cells from mice immunized with T. gondii insoluble antigens. TpM 3, TpM 6, and TpM 19 were characterized by the dye test, the latex agglutination test, two types of enzyme-linked immunosorbent assays, using either T. gondii supernatant antigens or T. gondii insoluble antigens, and immunoperoxidase staining. TpM 3, TpM ...

  18. Borderline disorder and attachment pathology.

    Science.gov (United States)

    West, M; Keller, A; Links, P; Patrick, J

    1993-02-01

    In this paper, the authors investigate the theoretical and empirical association between dysfunctions of the attachment system and borderline personality disorder. Attachment theory focuses on the maintenance of a sense of safety and security through a close personal relationship with a particular person. Based on a biological behavioural system, functional attachment relationships in adulthood rely on experiences and expectations of security within the relationship. These issues are also important to the definition and dynamics of borderline personality disorder. The dimensions and patterns of reciprocal attachment were compared with other scales measuring components of psychopathology and interpersonal relationships. In a sample of 85 female outpatients, only four of the attachment scales--feared loss, secure base, compulsive care-seeking and angry withdrawal--identified patients with high scores on a measure of borderline disorder. Of these four scales, feared loss had the predominant effect. These empirical results support the hypothesized relationship between dysfunctions of the attachment system and borderline disorder.

  19. Simplistic Attachment and Multispectral Imaging with Semiconductor Nanocrystals

    Directory of Open Access Journals (Sweden)

    Sara G. Becker-Catania

    2011-11-01

    Full Text Available Advances in spectral deconvolution technologies are rapidly enabling researchers to replace or enhance traditional epifluorescence microscopes with instruments capable of detecting numerous markers simultaneously in a multiplexed fashion. While significantly expediting sample throughput and elucidating sample information, this technology is limited by the spectral width of common fluorescence reporters. Semiconductor nanocrystals (NC’s are very bright, narrow band fluorescence emitters with great potential for multiplexed fluorescence detection, however the availability of NC’s with facile attachment chemistries to targeting molecules has been a severe limitation to the advancement of NC technology in applications such as immunocytochemistry and immunohistochemistry. Here we report the development of simple, yet novel attachment chemistries for antibodies onto NC’s and demonstrate how spectral deconvolution technology enables the multiplexed detection of 5 distinct NC-antibody conjugates with fluorescence emission wavelengths separated by as little as 20 nm.

  20. Attachment theory: Old and new approach

    OpenAIRE

    Polovina Nada

    2005-01-01

    The article is an attempt to present holistically the key concepts of attachment theory rediscovered for its potentials. The presented concepts include: narrow definition of attachment, behavioral control system of attachment, attachment working model and patterns of attachment. The concepts are presented in the context of child attachment theory and adult attachment theory, in addition to description of the development of attachment. Concepts, as well as developmental processes are presented...

  1. Attachment theory and therapeutic relationships

    OpenAIRE

    Boysan, Zehra

    2015-01-01

    The aims of this study were to examine the associations between current self-reported attachment styles, retrospective reports of childhood experiences, and the development of the therapeutic alliance. It was hypothesised that anxious and avoidant attachment would be correlated with negative childhood experiences and that both attachment anxiety and avoidance would be inversely correlated with the therapeutic alliance. The third hypothesis stated that negative childhood recollections would co...

  2. Adult attachment and psychosocial functioning

    OpenAIRE

    Pielage, Suzanne Brenda

    2006-01-01

    In the trilogy Attachment, Separation and Loss (1969, 1973, 1980), Bowlby theorized that early experiences with caregivers affect the quality of individuals’ later (romantic) relationships and, consequently, their mental health. The current thesis set out to examine the relationships between adult attachment and psychosocial functioning, predominately in the realm of close relationships. In the first part of the thesis, the focus lay on the assessment of the adult attachment construct. In Cha...

  3. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S.

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  4. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A; Thompson, Vicki S

    2013-02-26

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  5. Antibody profiling sensitivity through increased reporter antibody layering

    Energy Technology Data Exchange (ETDEWEB)

    Apel, William A.; Thompson, Vicki S

    2010-04-13

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  6. Antibody profiling sensitivity through increased reporter antibody layering

    International Nuclear Information System (INIS)

    A method for analyzing a biological sample by antibody profiling for identifying forensic samples or for detecting the presence of an analyte. In an embodiment of the invention, the analyte is a drug, such as marijuana, Cocaine (crystalline tropane alkaloid), methamphetamine, methyltestosterone, or mesterolone. The method comprises attaching antigens to a surface of a solid support in a preselected pattern to form an array wherein locations of the antigens are known; contacting the array with the biological sample such that a portion of antibodies in the sample reacts with and binds to the antigens in the array to form immune complexes; washing away antibodies that do form immune complexes; and detecting the immune complexes, to form an antibody profile. Forensic samples are identified by comparing a sample from an unknown source with a sample from a known source. Further, an assay, such as a test for illegal drug use, can be coupled to a test for identity such that the results of the assay can be positively correlated to the subject's identity.

  7. The molecular mechanism of Shiga toxin Stx2e neutralization by a single-domain antibody targeting the cell receptor-binding domain.

    Science.gov (United States)

    Lo, Alvin W H; Moonens, Kristof; De Kerpel, Maia; Brys, Lea; Pardon, Els; Remaut, Han; De Greve, Henri

    2014-09-01

    Shiga toxin Stx2e is the major known agent that causes edema disease in newly weaned pigs. This severe disease is characterized by neurological disorders, hemorrhagic lesions, and frequent fatal outcomes. Stx2e consists of an enzymatically active A subunit and five B subunits that bind to a specific glycolipid receptor on host cells. It is evident that antibodies binding to the A subunit or the B subunits of Shiga toxin variants may have the capability to inhibit their cytotoxicity. Here, we report the discovery and characterization of a VHH single domain antibody (nanobody) isolated from a llama phage display library that confers potent neutralizing capacity against Stx2e toxin. We further present the crystal structure of the complex formed between the nanobody (NbStx2e1) and the Stx2e toxoid, determined at 2.8 Å resolution. Structural analysis revealed that for each B subunit of Stx2e, one NbStx2e1 is interacting in a head-to-head orientation and directly competing with the glycolipid receptor binding site on the surface of the B subunit. The neutralizing NbStx2e1 can in the future be used to prevent or treat edema disease. PMID:25053417

  8. Attachment disorganization in different clinical groups: What underpins unresolved attachment?

    Directory of Open Access Journals (Sweden)

    Juen Florian

    2013-01-01

    Full Text Available This paper summarizes findings and clinical implications of research on attachment disorganization in diverse clinical groups. Disorganized/unresolved attachment is overrepresented in these groups compared to healthy control participants, but disorder specific characteristics of this attachment pattern are still poorly understood. The focus of this study was to explore defensive processes in participants whose narratives were classified as disorganized/unresolved using the Adult Attachment Projective Picture System (AAP. Besides the predominance of disorganized attachment, clinical participants demonstrated more “segregated system material” especially in stories representing aloneness and more “Personal Experience material” compared to healthy individuals. Within the disorganized/ unresolved clinical individuals, BPD and PTSD patients showed the highest proportion of attachment disorganization and were less able to use other attachment-related defenses to maintain organized. Furthermore, PTSD patients were emotionally overwhelmed by the projective attachment scenes compared to the other clinical groups as indexed by an incapacity to complete sections of the AAP. BPD and addicted patients were characterized by a high degree of self-other boundary confusion. Depressive and schizophrenic patients showed a high overall defensive intensity to remain organized.

  9. Monoclonal antibodies

    International Nuclear Information System (INIS)

    Monoclonal antibodies (MAbs) are antibodies having single specificity for a given antigen site (epitope). The development of hybridoma technology and the relative ease by which MAbs can be prepared has revolutionized many aspects of serological applications in diagnosis and differentiation of disease producing agents. The property of monospecificity offers advantages in diagnostic applications over polyclonal sera in that tests can be defined exactly with regard to the antigen detected and the affinity of reaction between the given antigenic site and the monoclonal reagent. In addition, MAbs offer better possibilities for test standardization, because the same reagent can be used in different laboratories. Such an MAb can be supplied by a central laboratory or 'grown' from hybridoma cells, ensuring that the resultant product is identical from laboratory to laboratory and that the part of the test involving the MAb reaction is the same. The methodologies for inoculation regimes, mice, cloning methods, selection of fusion partners, etc., have been validated extensively in developed country laboratories. The decision to establish a MAb production facility must be examined on a strict cost-benefit basis, since it is still expensive to produce a product. There are many MAbs available that should be sought to allow exploitation in developing tests. If a production facility is envisaged, it should produce reagents for national needs, i.e. there should be a clear problem oriented approach whereby exact needs are defined. In the field of veterinary applications, MAbs are the central reagent in many immunoassays based on the enzyme linked immunosorbent assay (ELISA). The development of specific tests for diagnosing diseases is dominated by MAbs and has been fuelled by a strong research base, mainly in developed countries allied to developing countries through the study of related diseases. Thus, there are very many assays dependent on MAbs, some of which form the basis of

  10. Introduction of new derivatives of biotin and DTPA for labeling of antibodies with 111 In ti detect malignant tumors

    International Nuclear Information System (INIS)

    Radiolabeled monoclonal antibodies, have created new innovations in diagnosis, research, and therapy of diseases in last 2 decades. One of the serious limitations of applications of radiolabeled antibodies in vivo is relatively low target to background activity. Various strategies have been proposed to solve this problem including pre-targeting methods that was suggested in 1989. Regarding importance of monoclonal antibodies and radioisotopes, based on pre-targeting strategy, we have introduced new derivative of biotin and DTPA to decrease background activity. DTPA-bio and new derivative (DTPA-bio-1 OX) were labeled with 111 In, labeled compounds and injected through tail veins into Balb/c mice, and percent of injected dose per gram of blood (% ID/g of blood ) was determined at 15, 30, 60, 120, 180 and 240 min after injection. Based on results, 111 In-DTPA-bio rapidly cleared from serum, indicating activity not bound to the target. While in the case of new derivative, by attaching 10 Adenine base (IOX) molecular weight of label is increased causing delayed clearance from serum. Therefore, there is enough time for label to accumulate in the target tissues. With advent of second generation of monoclonal antibodies and antibody engineering, pre targeting methods have changed greatly. It seems that derivatives we introduced will have and important role in new pre-targeting methods

  11. Attachment and ingestion of gonococci human neutrophils.

    Science.gov (United States)

    Dilworth, J A; Hendley, J O; Mandell, G L

    1975-03-01

    Previous studies have indirectly shown that type 1 gonococci are more resistant to phagocytosis by human neutrophils (PMN) than type 3 gonococci. Using phase contrast, fluorescent, and light microscopy, we directly quantitated PMN-gonococcal interaction, with emphasis on separating ingestion from attachment. PMN monolayers were incubated on slides with type 1 or type 3 gonococcal fluorescent antibody (FA). After methanol fixation, the FA-stained gonococci associated with PMN were cointed. Since the live PMN excludes FA, the FA-stained gonococci represent only extracellular gonococci. Methylene blue was then added to the smae slide to stain both ingested and surface attached gonococci. Using these methods, intracellular and extracellular cell-associated gonococci were quantitated under varying conditions. The numbers of methylene blue-stained cell-associated gonococci that were ingested were: with normal serum, 3.7 plus or minus 4.1 per cent for type 1 and 56.2 plus or minus 3.7 percent for type 3 (P smaller than 0.001); with heat-inactivated serum, 1.0 plus or minus 3.0 per cent for type 1 and 52.6 plus or minus 3.7 per cent for type 3 (P smaller than 0.001); with higher-titer anti-gonococcal antibody serum, 4.8 plus or minus 4.3 percent for type 1 and 64.0 plus or minus 1.6 per cent for type 3 (P smaller than 0.001). Thus, most type 3 organisms were ingested, but most type 1 gonococci were bound on the PMN surface.

  12. Protein Attachment on Nanodiamonds.

    Science.gov (United States)

    Lin, Chung-Lun; Lin, Cheng-Huang; Chang, Huan-Cheng; Su, Meng-Chih

    2015-07-16

    A recent advance in nanotechnology is the scale-up production of small and nonaggregated diamond nanoparticles suitable for biological applications. Using detonation nanodiamonds (NDs) with an average diameter of ∼4 nm as the adsorbents, we have studied the static attachment of three proteins (myoglobin, bovine serum albumin, and insulin) onto the nanoparticles by optical spectroscopy, mass spectrometry, and dynamic light scattering, and electrophoretic zeta potential measurements. Results show that the protein surface coverage is predominantly determined by the competition between protein-protein and protein-ND interactions, giving each protein a unique and characteristic structural configuration in its own complex. Specifically, both myoglobin and bovine serum albumin show a Langmuir-type adsorption behavior, forming 1:1 complexes at saturation, whereas insulin folds into a tightly bound multimer before adsorption. The markedly different adsorption patterns appear to be independent of the protein concentration and are closely related to the affinity of the individual proteins for the NDs. The present study provides a fundamental understanding for the use of NDs as a platform for nanomedical drug delivery. PMID:25815400

  13. Radiolabeled monoclonal antibodies: a review

    International Nuclear Information System (INIS)

    Since the description by Kohler and Milstein 1975 of their technique for producing monoclonal antibodies of predefined specificity, it has become a mainstay in most laboratories that utilize immunochemical techniques to study problems in basic, applied or clinical research. Paradoxically, the very success of monoclonal antibodies has generated a literature which is now so vast and scattered that it has become difficult to obtain a perspective. This brief review represents the distillation of many publications relating to the production and use of monoclonaal antibodies as radiopharmaceuticals. Significant advances were made possible in the last few years by combined developments in the fields of tumor-associated antigens and of monoclonal antibodies. In fact monoclonal antibodies against some well defined tumor-associated antigens, has led to significantly greater practical possibilities for producing highly specific radiolabeled antibodies as radiopharmaceuticals for diagnosis and therapy of human tumors. One of the main requirements of this methodology is the availability of stable radiopharmaceutical reagents which after labeling in vivo injection retain the capacity of specific interaction with the defined antigen and their molecular integrity. Since injection into human is the objetive of this kind of study all the specifications of radiopharmaceutical have to be fulfilled e.g. sterility, apirogenicity and absence of toxicity. (author)

  14. Diameters in preferential attachment models

    NARCIS (Netherlands)

    Dommers, S.; Van der Hofstad, R.; Hooghiemstra, G.

    2010-01-01

    In this paper, we investigate the diameter in preferential attachment (PA-) models, thus quantifying the statement that these models are small worlds. The models studied here are such that edges are attached to older vertices proportional to the degree plus a constant, i.e., we consider affine PA-mo

  15. Association between attachment and schizotypy

    OpenAIRE

    Dunne, Colm

    2011-01-01

    Background: The human genome project has affirmed the importance of non-genetic factors in human development. Attachment style is considered to be a diathesis for psychopathology and an important determinant regarding interpersonal functioning. Epidemiological research has indicated that there is significant aetiological continuity between symptoms of schizotypy and clinical symptoms of schizophrenia. Limited research has investigated the association between attachment and schi...

  16. Attachment, caring and prosocial behavior

    NARCIS (Netherlands)

    Erez, Ayelet

    2007-01-01

    The thesis focuses on 5 studies examining the role of adult attachment in volunteering by defining volunteerism as a form of caregiving. By that we suggest an effect of one behavioral system, attachment, on another, caring or prosocial behaviors in individual or group settings. Studies 1 and 2 ex

  17. Detection of Salmonella typhimurium using polyclonal antibody immobilized magnetostrictive biosensors

    Science.gov (United States)

    Guntupalli, R.; Hu, Jing; Lakshmanan, Ramji S.; Wan, Jiehui; Huang, Shichu; Yang, Hong; Barbaree, James M.; Huang, T. S.; Chin, Bryan A.

    2006-05-01

    Novel mass-sensitive, magnetostrictive sensors have a characteristic resonant frequency that can be determined by monitoring the magnetic flux emitted by the sensor in response to an applied, time varying, magnetic field. This magnetostrictive platform has a unique advantage over conventional sensor platforms in that measurement is wireless or remote. These biosensors can thus be used in-situ for detecting pathogens and biological threat agents. In this work, we have used a magnetostrictive platform immobilized with a polyclonal antibody (the bio-molecular recognition element) to form a biosensor for the detection of Salmonella typhimurium. Upon exposure to solutions containing Salmonella typhimurium bacteria, the bacteria were bound to the sensor and the additional mass of the bound bacteria caused a shift in the sensor's resonant frequency. Responses of the sensors to different concentrations of S. typhimurium were recorded and the results correlated with those obtained from scanning electron microscopy (SEM) images of samples. Good agreement between the measured number of bound bacterial cells (attached mass) and frequency shifts were obtained. The longevity and specificity of the selected polyclonal antibody were also investigated and are reported.

  18. Factors determining antibody distribution in tumors

    Science.gov (United States)

    Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

    2009-01-01

    The development of antibody therapies for cancer is increasing rapidly, primarily owing to their specificity. Antibody distribution in tumors is often extremely uneven, however, leading to some malignant cells being exposed to saturating concentrations of antibody, whereas others are completely untargeted. This is detrimental because large regions of cells escape therapy, whereas other regions might be exposed to suboptimal concentrations that promote a selection of resistant mutants. The distribution of antibody depends on a variety of factors, including dose, affinity, antigens per cell and molecular size. Because these parameters are often known or easily estimated, a quick calculation based on simple modeling considerations can predict the uniformity of targeting within a tumor. Such analyses should enable experimental researchers to identify in a straightforward way the limitations in achieving evenly distributed antibody, and design and test improved antibody therapeutics more rationally. PMID:18179828

  19. Monoclonal antibodies.

    Science.gov (United States)

    2009-01-01

    The ability to produce and exploit monoclonal antibodies (mAbs) has revolutionized many areas of biological sciences. The unique property of an mAb is that it is a single species of immunoglobulin (IG) molecule. This means that the specificity of the interaction of the paratopes on the IG, with the epitopes on an antigenic target, is the same on every molecule. This property can be used to great benefit in immunoassays to provide tests of defined specificity and sensitivity, which improve the possibilities of standardization. The performance of assays can often be determined relating the actual weight of antibody (hence the number of molecules) to the activity. Often the production of an mAb against a specific epitope is the only way that biological entities can be differentiated. This chapter outlines the areas involving the development of assays based on mAbs. The problems involved address include the physical aspects of mAbs and how they may affect assay design and also the implications of results based on monospecific reagents. Often these are not fully understood, leading to assays that are less than satisfactory, which does not justify the relatively high cost of preparing and screening of mAbs. There are many textbooks and reviews dealing with the preparation of mAbs, the principles involved, and various purification and manipulative methods for the preparation of fragments and conjugation. There has been little general information attempting to summarize the best approaches to assay design using mAbs. Much time can be wasted through bad planning, and this is particularly relevant to mAbs. A proper understanding of some basic principles is essential. It is beyond the scope of this chapter to discuss all aspects, but major areas are highlighted. PMID:19219589

  20. Direction-specific interactions control crystal growth by oriented attachment

    DEFF Research Database (Denmark)

    Li, Dongsheng; Nielsen, Michael H; Lee, Jonathan R.I.;

    2012-01-01

    The oriented attachment of molecular clusters and nanoparticles in solution is now recognized as an important mechanism of crystal growth in many materials, yet the alignment process and attachment mechanism have not been established. We performed high-resolution transmission electron microscopy...... using a fluid cell to directly observe oriented attachment of iron oxyhydroxide nanoparticles. The particles undergo continuous rotation and interaction until they find a perfect lattice match. A sudden jump to contact then occurs over less than 1 nanometer, followed by lateral atom-by-atom addition...... initiated at the contact point. Interface elimination proceeds at a rate consistent with the curvature dependence of the Gibbs free energy. Measured translational and rotational accelerations show that strong, highly direction-specific interactions drive crystal growth via oriented attachment....

  1. Direction-Specific Interactions Control Crystal Growth by Oriented Attachment

    Science.gov (United States)

    Li, Dongsheng; Nielsen, Michael H.; Lee, Jonathan R. I.; Frandsen, Cathrine; Banfield, Jillian F.; De Yoreo, James J.

    2012-05-01

    The oriented attachment of molecular clusters and nanoparticles in solution is now recognized as an important mechanism of crystal growth in many materials, yet the alignment process and attachment mechanism have not been established. We performed high-resolution transmission electron microscopy using a fluid cell to directly observe oriented attachment of iron oxyhydroxide nanoparticles. The particles undergo continuous rotation and interaction until they find a perfect lattice match. A sudden jump to contact then occurs over less than 1 nanometer, followed by lateral atom-by-atom addition initiated at the contact point. Interface elimination proceeds at a rate consistent with the curvature dependence of the Gibbs free energy. Measured translational and rotational accelerations show that strong, highly direction-specific interactions drive crystal growth via oriented attachment.

  2. Everything You Want To Know about Attachment.

    Science.gov (United States)

    Honig, Alice Sterling

    This paper discusses infant attachment, which it defines as a long-lasting emotional bond revealed when a child under stress seeks out and tries to stay close to a specific figure. The paper addresses: (1) What is attachment? Who are the pioneers in attachment theory?; (2) How do we notice attachment in action?; (3) Is attachment the only…

  3. [Antinuclear antibodies].

    Science.gov (United States)

    Cabiedes, Javier; Núñez-Álvarez, Carlos A

    2010-01-01

    Anti-nuclear antibodies (ANA) are immunoglobulin directed against autologous cell nuclear and cytoplasmic components. Besides the autoimmune ANA there are other ANA that can be detected in circulation, like natural and infectious ANA. Because of its high sensibility, detection of the ANA must be done by indirect immunofluorescence (IIF) as screening test and all of those positive samples are convenient to confirm its specificity by ELISA, western blot or other techniques. Positive ANA detected by IIF must be evaluated taking in to account the pattern and titer. The following recommended step is the specificity characterization (reactivity against extractable nuclear antigens [ENA], dsDNA, etc.) which is useful for the diagnosis and follow up of patients with autoimmune diseases, and by such reasoning, its detection must be performed in an orderly and reasonable way using guides or strategies focused to the good use and interpretation of the autoantibodies. The objective of this review is to present a compilation of the literature and our experience in the detection and study of the ANA.

  4. Enzyme-linked immunosorbent assay for quantitation of attachment and ingestion stages of bacterial phagocytosis.

    OpenAIRE

    Athamna, A; Ofek, I

    1988-01-01

    Research on phagocytosis of bacteria is often hampered by the inability to distinguish quantitatively between bacteria that have been ingested by phagocytic cells and those which are attached to the surface of the cells. A method using the enzyme-linked immunosorbent assay technique to simply and accurately measure the rate of bacterial ingestion by phagocytic cells is described. The method is based on the ability of antibacterial antibodies to bind to bacteria attached to but not internalize...

  5. Attachment at work and performance.

    Science.gov (United States)

    Neustadt, Elizabeth A; Chamorro-Premuzic, Tomas; Furnham, Adrian

    2011-09-01

    This paper examines the relations between self-reported attachment orientation at work and personality, self-esteem, trait emotional intelligence (aka emotional self-efficacy), and independently assessed career potential and job performance. Self-report data were collected from 211 managers in an international business in the hospitality industry; independent assessments of these managers' job performance and career potential were separately obtained from the organization. A self-report measure of romantic attachment was adapted for application in the work context; a two-factor solution was found for this measure. Secure/autonomous attachment orientation at work was positively related to self-esteem, trait emotional intelligence, extraversion, agreeableness, and conscientiousness, and also to job performance. Not only was secure/autonomous attachment orientation at work statistically predictive of job performance, but the new measure also made a distinct contribution, beyond conscientiousness, to this prediction. PMID:21838647

  6. Social attachments and traumatic stress

    Directory of Open Access Journals (Sweden)

    Richard A. Bryant

    2016-03-01

    Full Text Available The extent to which we engage with our social world has been central to our survival as a species and, accordingly, is relevant to how we cope with trauma and adversity. This review summarises current knowledge about the importance of social connections from an evolutionary perspective, as well as integrating this with a discussion of prevailing attachment theories. Experimental research supporting the potential benefit of attachments for managing adversity are presented, along with a review of how these benefits are moderated by individual differences in attachment style. The potential impact of trauma on attachment systems, and the manner in which this can compound trauma stress is discussed. Finally, a broader overview of social network analysis is introduced and it is proposed that a more sociocentric framework of trauma response would promote a fuller understanding of how social processes moderate trauma response.

  7. Electron attachment to fluorocarbon radicals

    Science.gov (United States)

    Shuman, Nicholas

    2014-10-01

    Most plasma environments contain populations of short-lived species such as radicals, the chemistry of which can have significant effects on the overall chemistry of the system. However, few experimental measurements of the kinetics of electron attachment to radicals exist due to the inherent difficulties of working with transient species. Calculations from first principles have been attempted, but are arduous and, because electron attachment is so sensitive to the specifics of the potential surface, their accuracy has not been established. Electron attachment to small fluorocarbon radicals is particularly important, as the data are needed for predictive modeling of plasma etching of semiconductor materials, a key process in the industrial fabrication of microelectronics. We have recently developed a novel flowing afterglow technique to measure several types of otherwise difficult to study plasma processes, including thermal electron attachment to radicals. Variable Electron and Neutral Density Attachment Mass Spectrometry (VENDAMS) exploits dissociative electron attachment in a weakly ionized plasma as a radical source. Here, we apply VENDAMS to a series of halofluorocarbon precursors in order to measure the kinetics of thermal electron attachment to fluorocarbon radicals. Results are presented for CF2, CF3, C2F5,C2F3,1-C3F7, 2-C3F7, and C3F5 from 300 K to 900 K. Both the magnitude and the temperature dependences of rate coefficients as well as product branching between associative and dissociative attachment are highly system specific; however, thermal attachment to all species is inefficient, never exceeding 5% of the collision rate. The data are analyzed using a recently developed kinetic modeling approach, which uses extended Vogt-Wannier theory as a starting point, accounts for dynamic effects such as coupling between the electron and nuclear motions through empirically validated functional forms, and finally uses statistical theory to determine the fate of

  8. Antibody-Directed Phototherapy (ADP

    Directory of Open Access Journals (Sweden)

    M. Adil Butt

    2013-04-01

    Full Text Available Photodynamic therapy (PDT is a clinically-approved but rather under-exploited treatment modality for cancer and pre-cancerous superficial lesions. It utilises a cold laser or LED to activate a photochemical reaction between a light activated drug (photosensitiser-drug and oxygen to generate cytotoxic oxygen species. These free radical species damage cellular components leading to cell death. Despite its benefits, the complexity, limited potency and side effects of PDT have led to poor general usage. However, the research area is very active with an increasing understanding of PDT-related cell biology, photophysics and significant progress in molecular targeting of disease. Monoclonal antibody therapy is maturing and the next wave of antibody therapies includes antibody-drug conjugates (ADCs, which promise to be more potent and curable. These developments could lift antibody-directed phototherapy (ADP to success. ADP promises to increase specificity and potency and improve drug pharmacokinetics, thus delivering better PDT drugs whilst retaining its other benefits. Whole antibody conjugates with first generation ADP-drugs displayed problems with aggregation, poor pharmacokinetics and loss of immuno-reactivity. However, these early ADP-drugs still showed improved selectivity and potency. Improved PS-drug chemistry and a variety of conjugation strategies have led to improved ADP-drugs with retained antibody and PS-drug function. More recently, recombinant antibody fragments have been used to deliver ADP-drugs with superior drug loading, more favourable pharmacokinetics, enhanced potency and target cell selectivity. These improvements offer a promise of better quality PDT drugs.

  9. Molecular polygamy: The promiscuity of l-phenylalanyl-tRNA-synthetase triggers misincorporation of meta- and ortho-tyrosine in monoclonal antibodies expressed by Chinese hamster ovary cells.

    Science.gov (United States)

    Popp, Oliver; Larraillet, Vincent; Kettenberger, Hubert; Gorr, Ingo H; Hilger, Maximiliane; Lipsmeier, Florian; Zeck, Anne; Beaucamp, Nicola

    2015-06-01

    In-depth analytical characterization of biotherapeutics originating from different production batches is mandatory to ensure product safety and consistent molecule efficacy. Previously, we have shown unintended incorporation of tyrosine (Tyr) and leucine/isoleucine (Leu/Ile) at phenylalanine (Phe) positions in a recombinant produced monoclonal antibody (mAb) using an orthogonal MASCOT/SIEVE based approach for mass spectrometry data analysis. The misincorporation could be avoided by sufficient supply of phenylalanine throughout the process. Several non-annotated signals in the primarily chromatographic peptide separation step for apparently single Phe→Tyr sequence variants (SVs) suggest a role for isobar tyrosine isoforms. Meta- and ortho-Tyr are spontaneously generated during aerobic fed-batch production processes using Chinese hamster ovary (CHO) cell lines. Process induced meta- and ortho-Tyr but not proteinogenic para-Tyr are incorporated at Phe locations in Phe-starved CHO cultures expressing a recombinant mAb. Furthermore, meta- and ortho-Tyr are preferably misincorporated over Leu. Structural modeling of the l-phenylalanyl-tRNA-synthetase (PheRS) substrate activation site indicates a possible fit of non-cognate ortho-Tyr and meta-Tyr substrates. Dose-dependent misincorporations of Tyr isoforms support the hypothesis that meta- and ortho-Tyr are competing, alternative substrates for PheRS in CHO processes. Finally, easily accessible at-line surrogate markers for Phe→Tyr SV formation in biotherapeutic production were defined by the calculation of critical ratios for meta-Tyr/Phe and ortho-Tyr/Phe to support early prediction of SV probability, and finally, to allow for immediate process controlled Phe→Tyr SV prevention.

  10. Attachment Narratives in Refugee Children

    DEFF Research Database (Denmark)

    De Haene, L.; Dalgård, Nina Thorup; Montgomery, E.;

    2013-01-01

    J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study.......J Trauma Stress. 2013 Jun;26(3):413-7. doi: 10.1002/jts.21820. Attachment narratives in refugee children: interrater reliability and qualitative analysis in pilot findings from a two-site study....

  11. Antibodies: an alternative for antibiotics?

    Science.gov (United States)

    Berghman, L R; Abi-Ghanem, D; Waghela, S D; Ricke, S C

    2005-04-01

    In 1967, the success of vaccination programs, combined with the seemingly unstoppable triumph of antibiotics, prompted the US Surgeon General to declare that "it was time to close the books on infectious diseases." We now know that the prediction was overly optimistic and that the fight against infectious diseases is here to stay. During the last 20 yr, infectious diseases have indeed made a staggering comeback for a variety of reasons, including resistance against existing antibiotics. As a consequence, several alternatives to antibiotics are currently being considered or reconsidered. Passive immunization (i.e., the administration of more or less pathogen-specific antibodies to the patient) prior to or after exposure to the disease-causing agent is one of those alternative strategies that was almost entirely abandoned with the introduction of chemical antibiotics but that is now gaining interest again. This review will discuss the early successes and limitations of passive immunization, formerly referred to as "serum therapy," the current use of antibody administration for prophylaxis or treatment of infectious diseases in agriculture, and, finally, recent developments in the field of antibody engineering and "molecular farming" of antibodies in various expression systems. Especially the potential of producing therapeutic antibodies in crops that are routine dietary components of farm animals, such as corn and soy beans, seems to hold promise for future application in the fight against infectious diseases. PMID:15844826

  12. Integrated molecular targeting of IGF1R and HER2 surface receptors and destruction of breast cancer cells using single wall carbon nanotubes

    Energy Technology Data Exchange (ETDEWEB)

    Shao Ning [Delaware MEMS and Nanotechnology Laboratory, Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716 (United States); Lu Shaoxin [Delaware MEMS and Nanotechnology Laboratory, Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716 (United States); Wickstrom, Eric [Department of Biochemistry and Molecular Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Panchapakesan, Balaji [Delaware MEMS and Nanotechnology Laboratory, Department of Electrical and Computer Engineering, University of Delaware, Newark, DE 19716 (United States)

    2007-08-08

    Molecular targeting and photodynamic therapy have shown great potential for selective cancer therapy. We hypothesized that monoclonal antibodies that are specific to the IGF1 receptor and HER2 cell surface antigens could be bound to single wall carbon nanotubes (SWCNT) in order to concentrate SWCNT on breast cancer cells for specific near-infrared phototherapy. SWCNT functionalized with HER2 and IGF1R specific antibodies showed selective attachment to breast cancer cells compared to SWCNT functionalized with non-specific antibodies. After the complexes were attached to specific cancer cells, SWCNT were excited by {approx}808 nm infrared photons at {approx}800 mW cm{sup -2} for 3 min. Viability after phototherapy was determined by Trypan blue exclusion. Cells incubated with SWCNT/non-specific antibody hybrids were still alive after photo-thermal treatment due to the lack of SWNT binding to the cell membrane. All cancerous cells treated with IGF1R and HER2 specific antibody/SWCNT hybrids and receiving infrared photons showed cell death after the laser excitation. Quantitative analysis demonstrated that all the cells treated with SWCNT/IGF1R and HER2 specific antibody complex were completely destroyed, while more than 80% of the cells with SWCNT/non-specific antibody hybrids remained alive. Following multi-component targeting of IGF1R and HER2 surface receptors, integrated photo-thermal therapy in breast cancer cells led to the complete destruction of cancer cells. Functionalizing SWCNT with antibodies in combination with their intrinsic optical properties can therefore lead to a new class of molecular delivery and cancer therapeutic systems.

  13. Mycoplasma pneumoniae Infection: Role of a Surface Protein in the Attachment Organelle

    Science.gov (United States)

    Hu, P. C.; Cole, R. M.; Huang, Y. S.; Graham, J. A.; Gardner, D. E.; Collier, A. M.; Clyde, W. A.

    1982-04-01

    Attachment of Mycoplasma pneumoniae to host cells by means of a specialized terminus initiates infection. Monoclonal antibodies to a surface protein (P1) inhibit this process, and react with a region of the tip covered with peplomer-like particles. Since antibodies against the P1 protein are generated by natural and experimental infection and by immunization, the substance may be an important determinant of protective immunity.

  14. Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the β-Subunit of Phycocyanin in Arthrospira platensis FACHB314.

    Science.gov (United States)

    Wu, Fei; Zang, Xiaonan; Zhang, Xuecheng; Zhang, Ran; Huang, Xiaoyun; Hou, Lulu; Jiang, Minjie; Liu, Chang; Pang, Chunhong

    2016-01-01

    A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB) producing genes (hoxI and pcyA), while the other contained the gene of the β-Subunit of phycobiliprotein (cpcB) and the lyase gene (cpcU, cpcS, or cpcU/S) were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent β-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the β-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314. PMID:26999083

  15. Molecular Cloning of cpcU and Heterodimeric Bilin Lyase Activity Analysis of CpcU and CpcS for Attachment of Phycocyanobilin to Cys-82 on the β-Subunit of Phycocyanin in Arthrospira platensis FACHB314

    Directory of Open Access Journals (Sweden)

    Fei Wu

    2016-03-01

    Full Text Available A new bilin lyase gene cpcU was cloned from Arthrospira platensis FACHB314 to study the assembly of the phycocyanin β-Subunit. Two recombinant plasmids, one contained the phycocyanobilin (PCB producing genes (hoxI and pcyA, while the other contained the gene of the β-Subunit of phycobiliprotein (cpcB and the lyase gene (cpcU, cpcS, or cpcU/S were constructed and separately transferred into Escherichia coli in order to test the activities of relevant lyases for catalyzing PCB addition to CpcB during synthesizing fluorescent β-PC of A. platensis FACHB314. The fluorescence intensity examination showed that Cys-82 maybe the active site for the β-Subunit binding to PCBs and the attachment could be carried out by CpcU, CpcS, or co-expressed cpcU/S in A. platensis FACHB314.

  16. Site-specific integration of the temperate bacteriophage phi adh into the Lactobacillus gasseri chromosome and molecular characterization of the phage (attP) and bacterial (attB) attachment sites.

    Science.gov (United States)

    Raya, R R; Fremaux, C; De Antoni, G L; Klaenhammer, T R

    1992-01-01

    The temperate bacteriophage phi adh integrates its genome into the chromosomal DNA of Lactobacillus gasseri ADH by a site-specific recombination process. Southern hybridization analysis of BclI-digested genomic DNA from six relysogenized derivatives of the prophage-cured strain NCK102 displayed phage-chromosomal junction fragments identical to those of the lysogenic parent. The phi adh attachment site sequence, attP, was located within a 365-bp EcoRI-HindIII fragment of phage phi adh. This fragment was cloned and sequenced. DNA sequence analysis revealed striking features common to the attachment sites of other site-specific recombination systems: five direct repeats of the sequence TGTCCCTTTT(C/T) and a 14-bp inverted repeat. Oligonucleotides derived from the sequence of the attP-containing fragment enabled us to amplify predicted junction fragment sequences and thus to identify attL, attR, and attB. The core region was defined as the 16-bp sequence TACACTTCTTAGGAGG. Phage-encoded functions essential for site-specific insertion of phage phi adh were located in a 4.5-kb BclI fragment. This fragment was cloned in plasmid pSA34 to generate the insertional vector pTRK182. Plasmid pTRK182 was introduced into L. gasseri NCK102 by electroporation. Hybridization analysis showed that a single copy of pTRK182 had integrated at the attB site of the NCK102 erythromycin-resistant transformants. This is the first site-specific recombination system described in lactobacilli, as well as the first attP-based site-specific integration vector constructed for L. gasseri ADH. Images PMID:1512192

  17. Nucleotide and Predicted Amino Acid Sequence-Based Analysis of the Avian Metapneumovirus Type C Cell Attachment Glycoprotein Gene: Phylogenetic Analysis and Molecular Epidemiology of U.S. Pneumoviruses

    Science.gov (United States)

    Alvarez, Rene; Lwamba, Humphrey M.; Kapczynski, Darrell R.; Njenga, M. Kariuki; Seal, Bruce S.

    2003-01-01

    A serologically distinct avian metapneumovirus (aMPV) was isolated in the United States after an outbreak of turkey rhinotracheitis (TRT) in February 1997. The newly recognized U.S. virus was subsequently demonstrated to be genetically distinct from European subtypes and was designated aMPV serotype C (aMPV/C). We have determined the nucleotide sequence of the gene encoding the cell attachment glycoprotein (G) of aMPV/C (Colorado strain and three Minnesota isolates) and predicted amino acid sequence by sequencing cloned cDNAs synthesized from intracellular RNA of aMPV/C-infected cells. The nucleotide sequence comprised 1,321 nucleotides with only one predicted open reading frame encoding a protein of 435 amino acids, with a predicted Mr of 48,840. The structural characteristics of the predicted G protein of aMPV/C were similar to those of the human respiratory syncytial virus (hRSV) attachment G protein, including two mucin-like regions (heparin-binding domains) flanking both sides of a CX3C chemokine motif present in a conserved hydrophobic pocket. Comparison of the deduced G-protein amino acid sequence of aMPV/C with those of aMPV serotypes A, B, and D, as well as hRSV revealed overall predicted amino acid sequence identities ranging from 4 to 16.5%, suggesting a distant relationship. However, G-protein sequence identities ranged from 72 to 97% when aMPV/C was compared to other members within the aMPV/C subtype or 21% for the recently identified human MPV (hMPV) G protein. Ratios of nonsynonymous to synonymous nucleotide changes were greater than one in the G gene when comparing the more recent Minnesota isolates to the original Colorado isolate. Epidemiologically, this indicates positive selection among U.S. isolates since the first outbreak of TRT in the United States. PMID:12682171

  18. 分子印迹在仿生免疫吸附分析中的应用%Molecularly Imprinted Polymers as Antibody Alternatives in Sorbent Immunoassays

    Institute of Scientific and Technical Information of China (English)

    吕春晖; 王硕; 方国臻; 汤轶伟; 王岁楼

    2012-01-01

    Molecularly imprinted polymer(MIP),a material which owns artificially-created binding sites coupled with several distinct advantages such as high chemical,mechanical and thermal stability,robust,easy preparation,low cost and reusable.MIP as mimic in pseudo-immunoassays have attracted considerable attention over the last few years.The advances in molecularly imprinted sorbent immunoassays(MIAs) are reviewed from radioligand immunoassays to non-radioligand immunoassays,and emphasize on the promotion which homogeneous immunoassay systems and new synthesis methods bring.It is shown that the perceived disadvantages of MIP can be ignored in MIAs.The existing problems and prospects of MIAs are also described.%分子印迹聚合物是一种含特异性识别位点的高分子材料,具有高稳定性、低成本、制备简单和可重复利用等特点,常被作为仿生抗体应用于免疫分析。本文综述了分子印迹免疫吸附分析(molecularlyimprinted sorbent immunoassays,MIAs)的研究进展,介绍了以不同标记物为探针的仿生免疫分析方法的发展,着重介绍了均相免疫分析系统与分子印迹聚合物的新型合成方法在MIAs中的应用。最后,本文指出分子印迹聚合物的一些缺点并没有阻碍其在免疫吸附分析中的应用,并对MIAs仍然存在的问题和发展前景进行了分析。

  19. Biosensing made easy with PEG-targeted bi-specific antibodies.

    Science.gov (United States)

    Raftery, Lyndon J; Grewal, Yadveer S; Howard, Christopher B; Jones, Martina L; Shiddiky, Muhammad J A; Carrascosa, Laura G; Thurecht, Kristofer J; Mahler, Stephen M; Trau, Matt

    2016-04-28

    Whilst recent advances in nanotechnology have yielded many new biosensing capabilities, innovative biological attachment and detection modalities remain relatively underdeveloped. Bi-specific antibodies (bsAbs)--which exhibit binding capability for two separate targets--offer an inherent advantage over conventional antibody reagents by significantly simplifying sensor surface preparation. Herein, we report the deployment of bsAbs for simultaneous attachment to a polymer-coated transducer and label-free, electrochemical (EC) detection of target antigens. PMID:27045479

  20. Activating Attachments Reduces Memories of Traumatic Images.

    Science.gov (United States)

    Bryant, Richard A; Foord, Rachael

    2016-01-01

    Emotional memories, and especially intrusive memories, are a common feature of many psychological disorders, and are overconsolidated by stress. Attachment theory posits that activation of mental representations of attachment figures can reduce stress and boost coping. This study tested the proposition that attachment activation would reduce consolidation of emotional and intrusive memories. Sixty-seven undergraduate students viewed subliminal presentations of traumatic and neutral images, which were preceded by subliminal presentations of either attachment-related images or non-attachment-related images; free recall and intrusive memories were assessed two days later. Participants with low avoidant attachment tendencies who received the attachment primes recalled fewer memories and reported fewer intrusions than those who received the non-attachment primes. Unexpectedly, those with high anxious attachment tendencies reported fewer memories. These findings generally accord with attachment theory, and suggest that consolidation of emotional memories can be moderated by activation of attachment representations. PMID:27631498

  1. Dissecting the Role of Anti-ganglioside Antibodies in Guillain-Barré Syndrome: an Animal Model Approach.

    Science.gov (United States)

    Asthana, Pallavi; Vong, Joaquim Si Long; Kumar, Gajendra; Chang, Raymond Chuen-Chung; Zhang, Gang; Sheikh, Kazim A; Ma, Chi Him Eddie

    2016-09-01

    Guillain-Barré syndrome (GBS) is an autoimmune polyneuropathy disease affecting the peripheral nervous system (PNS). Most of the GBS patients experienced neurological symptoms such as paresthesia, weakness, pain, and areflexia. There are also combinations of non-neurological symptoms which include upper respiratory tract infection and diarrhea. One of the major causes of GBS is due largely to the autoantibodies against gangliosides located on the peripheral nerves. Gangliosides are sialic acid-bearing glycosphingolipids consisting of a ceramide lipid anchor with one or more sialic acids attached to a neutral sugar backbone. Molecular mimicry between the outer components of oligosaccharide of gangliosides on nerve membrane and lipo-oligosaccharide of microbes is thought to trigger the autoimmunity. Intra-peritoneal implantation of monoclonal ganglioside antibodies secreting hybridoma into animals induced peripheral neuropathy. Recent studies demonstrated that injection of synthesized anti-ganglioside antibodies raised by hybridoma cells into mice initiates immune response against peripheral nerves, and eventually failure in peripheral nerve regeneration. Accumulating evidences indicate that the conjugation of anti-ganglioside monoclonal antibodies to activating FcγRIII present on the circulating macrophages inhibits axonal regeneration. The activation of RhoA signaling pathways is also involved in neurite outgrowth inhibition. However, the link between these two molecular events remains unresolved and requires further investigation. Development of anti-ganglioside antagonists can serve as targeted therapy for the treatment of GBS and will open a new approach of drug development with maximum efficacy and specificity. PMID:26374552

  2. Hamiltonian Dynamics of Preferential Attachment

    CERN Document Server

    Zuev, Konstantin; Krioukov, Dmitri

    2015-01-01

    Prediction and control of network dynamics are grand-challenge problems in network science. The lack of understanding of fundamental laws driving the dynamics of networks is among the reasons why many practical problems of great significance remain unsolved for decades. Here we study the dynamics of networks evolving according to preferential attachment, known to approximate well the large-scale growth dynamics of a variety of real networks. We show that this dynamics is Hamiltonian, thus casting the study of complex networks dynamics to the powerful canonical formalism, in which the time evolution of a dynamical system is described by Hamilton's equations. We derive the explicit form of the Hamiltonian that governs network growth in preferential attachment. This Hamiltonian turns out to be nearly identical to graph energy in the configuration model, which shows that the ensemble of random graphs generated by preferential attachment is nearly identical to the ensemble of random graphs with scale-free degree d...

  3. ON THE NOTION OF SYNERGY OF MONOCLONAL ANTIBODIES AS DRUGS

    Directory of Open Access Journals (Sweden)

    Michael Sela

    2013-08-01

    Full Text Available History of developing synergy between monoclonal antibodies, anti-tumor activity of monoclonal antibodies against tyrosine-kinases receptors EGFR/ErbB-1 and HER2/ErbB-2 as well as growth factor VEGF in various combinations are considered in the article. There were proposed hypotheses about potential molecular mechanisms underlay synergy between monoclonal antibodies (for homo- and hetero combinations of antibodies appropriately specific for antigenic determinants on the same or different receptors. Future trends in researches necessary to deeper understanding causes of this phenomenon and perspectives for practical application of monoclonal antibodies acted synergistically as immunotherapeutic drugs for human tumors treatment are reviewed.

  4. Diameters in preferential attachment models

    OpenAIRE

    Dommers, S.; van der Hofstad, R.; Hooghiemstra, G.

    2010-01-01

    In this paper, we investigate the diameter in preferential attachment (PA-) models, thus quantifying the statement that these models are small worlds. The models studied here are such that edges are attached to older vertices proportional to the degree plus a constant, i.e., we consider affine PA-models. There is a substantial amount of literature proving that, quite generally, PA-graphs possess power-law degree sequences with a power-law exponent \\tau>2. We prove that the diameter of the PA-...

  5. Structural Interfaces and Attachments in Biology

    CERN Document Server

    Birman, Victor; Genin, Guy

    2013-01-01

    Attachment of dissimilar materials in engineering and surgical practice is a perennial challenge. Bimaterial attachment sites are common locations for injury, repeated injury, and mechanical failure. Nature presents several highly effective solutions to the challenge of bimaterial attachment that differ from those found in engineering practice. Structural Interfaces and Attachments in Biology describes the attachment of dissimilar materials from multiple perspectives. The text will simultaneously elucidate natural bimaterial attachments and outline engineering principles underlying successful attachments to the communities of tissue engineers and surgeons. Included an in-depth analysis of the biology of attachments in the body and mechanisms by which robust attachments are formed, a review of current concepts of attaching dissimilar materials in surgical practice and a discussion of bioengineering approaches that are currently being developed. This book also: Provides the first comprehensive treatment of phys...

  6. Fermentanomics informed amino acid supplementation of an antibody producing mammalian cell culture.

    Science.gov (United States)

    Read, Erik K; Bradley, Scott A; Smitka, Tim A; Agarabi, Cyrus D; Lute, Scott C; Brorson, Kurt A

    2013-01-01

    Fermentanomics, or a global understanding of a culture state on the molecular level empowered by advanced techniques like NMR, was employed to show that a model hybridoma culture supplied with glutamine and glucose depletes aspartate, cysteine, methionine, tryptophan, and tyrosine during antibody production. Supplementation with these amino acids prevents depletion and improves culture performance. Furthermore, no significant changes were observed in the distribution of glycans attached to the IgG3 in cultures supplemented with specific amino acids, arguing that this strategy can be implemented without fear of impact on important product quality attributes. In summary, a targeted strategy of quantifying media components and designing a supplementation strategy can improve bioprocess cell cultures when enpowered by fermentanomics tools.

  7. Attachment patterns and separation anxiety symptom

    OpenAIRE

    Sakineh - Mofrad; Rohani - Abdullah; Ikechkwu - Uba

    2010-01-01

    Literature suggests that child attachment and anxiety symptoms are related. One purpose of the present study was to assess whether attachment patterns related differently to separation anxiety symptoms (fear of being alone, and fear of abandonment). Three attachment patterns assessed were secure, avoidant and ambivalent attachment. Findings indicated that ambivalent attachment was most consistently related with higher separation anxiety symptom. And also, different associations were found bet...

  8. Bar overdentures utilizing the Locator attachment.

    Science.gov (United States)

    Schneider, A L; Kurtzman, G M

    2001-01-01

    Implant-retained overdentures are a restorative option for both the fully and partially edentulous arches. A new attachment, the Locator, which features a reduced interarch requirement and the advantage of built-in guide planes providing precise insertion, is described. The Locator is an advancement in attachment technology, with an improved design combined from the best features of a ball attachment, an ERA attachment, and a cap attachment.

  9. PRECISION ATTACHMENTS; APPLICATIONS AND LIMITATIONS

    Directory of Open Access Journals (Sweden)

    Prabhakar

    2012-12-01

    Full Text Available ABSTRACT: A unique concern of a removable denture when compare d to others is retention. Retention is the ability of the prosthesis to resist the movement of denture away from the supporting tissues/teeth. The component of removable d enture which provides retention is called as direct retainer. 1,3,4 A direct retainer can be either an extracoronal or intracoronal retainer. Extracoronal direct retainer uses mechanical resistance to displa cement through components placed on external surface of abutment teeth. Intracoronal retainer is either cast or attached to tally within the restored natural contours of an abutment tooth. 1 One of the main drawbacks of extracoronal retainers used in partial dentures is visibility. Many patients find themselves in an aest hetically compromised state when these retainers are placed on teeth in visible area. Preci sion attachments provide solution for this problem. Also, precision attachments provide better ve rtical support and better stimulation to the underlying tissue through intermittent vertical massage. 1,9 Although the history of intracoronal retainers goes back to 5 th and 4 th centuries BC, technically more sound developments began in early 2 0 th century AD, with Dr. Herman E. S. Chayes formulating the principle of internal attachme nt in 1906. Since then precision attachments are playing an important role in removabl e and fixed partial denture, conventional and implant supported overdenture. 9

  10. Adult attachment and psychosocial functioning

    NARCIS (Netherlands)

    Pielage, Suzanne Brenda

    2006-01-01

    In the trilogy Attachment, Separation and Loss (1969, 1973, 1980), Bowlby theorized that early experiences with caregivers affect the quality of individuals’ later (romantic) relationships and, consequently, their mental health. The current thesis set out to examine the relationships between adult a

  11. Virus-specific antibodies in sera from patients with genital herpes simplex virus infection.

    OpenAIRE

    Zweerink, H J; Corey, L

    1982-01-01

    Virus-specific antibodies against a number of herpes simplex virus type 2 antigens were determined by radioimmunoprecipitation assays in sequential serum samples obtained from 12 patients with initial genital herpes simplex virus infection. The progressive appearance of antibodies to virus-specific antigens was observed; antibodies against a 130,000-molecular-weight glycoprotein complex appeared first, followed by antibodies against the major nucleocapsid polypeptide and then antibodies again...

  12. IgE antibody responses in schistosomiasis measured by a radioallergosorbent test

    International Nuclear Information System (INIS)

    Helminth infections are associated with the production of unusually high concentrations of circulating IgE antibody. Assays for IgE antibodies should provide useful approaches for the study of protective immunity and may also be of use in serodiagnosis of diseases induced by helminths. The radioallergosorbent test is carried out by attaching the antigen or allergen to an insoluble supportive material, allowing the IgE antibodies in the test serum to react with excess bound antigen, and then estimating the IgE antibody bound by its reaction with 125I-labelled goat anti-human IgE antibody

  13. Monoclonal antibodies and cancer

    International Nuclear Information System (INIS)

    The usefulness of radiolabeled monoclonal antibodies for imaging and treatment of human (ovarian) cancer was investigated. A review of tumor imaging with monoclonal antibodies is presented. Special attention is given to factors that influence the localization of the antibodies in tumors, isotope choice and methods of radiolabeling of the monoclonal antibodies. Two monoclonal antibodies, OC125 and OV-TL3, with high specificity for human epithelial ovarian cancer are characterized. A simple radio-iodination technique was developed for clinical application of the monoclonal antibodies. The behavior of monoclonal antibodies in human tumor xenograft systems and in man are described. Imaging of tumors is complicated because of high background levels of radioactivity in other sites than the tumor, especially in the bloodpool. A technique was developed to improve imaging of human tumor xenographs in nude mice, using subtraction of a specific and a non-specific antibody, radiolabeled with 111In, 67Ga and 131I. To investigate the capability of the two monoclonal antibodies, to specifically localize in human ovarian carcinomas, distribution studies in mice bearing human ovarian carcinoma xenografts were performed. One of the antibodies, OC125, was used for distribution studies in ovarian cancer patients. OC125 was used because of availability and approval to use this antibody in patients. The same antibody was used to investigate the usefulness of radioimmunoimaging in ovarian cancer patients. The interaction of injected radiolabeled antibody OC125 with circulating antigen and an assay to measure the antibody response in ovarian cancer patients after injection of the antibody is described. 265 refs.; 30 figs.; 19 tabs

  14. [VGKC-complex antibodies].

    Science.gov (United States)

    Watanabe, Osamu

    2013-04-01

    Various antibodies are associated with voltage-gated potassium channels (VGKCs). Representative antibodies to VGKCs were first identified by radioimmunoassays using radioisotope-labeled alpha-dendrotoxin-VGKCs solubilized from rabbit brain. These antibodies were detected only in a proportion of patients with acquired neuromyotonia (Isaacs' syndrome). VGKC antibodies were also detected in patients with Morvan's syndrome and in those with a form of autoimmune limbic encephalitis. Recent studies indicated that the "VGKC" antibodies are mainly directed toward associated proteins (for example LGI-1 and CASPR-2) that complex with the VGKCs themselves. The "VGKC" antibodies are now commonly known as VGKC-complex antibodies. In general, LGI-1 antibodies are most commonly detected in patients with limbic encephalitis with syndrome of inappropriate secretion of antidiuretic hormone. CASPR-2 antibodies are present in the majority of patients with Morvan's syndrome. These patients develop combinations of CNS symptoms, autonomic dysfunction, and peripheral nerve hyperexcitability. Furthermore, VGKC-complex antibodies are tightly associated with chronic idiopathic pain. Hyperexcitability of nociceptive pathways has also been implicated. These antibodies may be detected in sera of some patients with neurodegenerative diseases (for example, amyotrophic lateral sclerosis and Creutzfeldt-Jakob disease).

  15. Baculovirus display of functional antibody Fab fragments.

    Science.gov (United States)

    Takada, Shinya; Ogawa, Takafumi; Matsui, Kazusa; Suzuki, Tasuku; Katsuda, Tomohisa; Yamaji, Hideki

    2015-08-01

    The generation of a recombinant baculovirus that displays antibody Fab fragments on the surface was investigated. A recombinant baculovirus was engineered so that the heavy chain (Hc; Fd fragment) of a mouse Fab fragment was expressed as a fusion to the N-terminus of baculovirus gp64, while the light chain of the Fab fragment was simultaneously expressed as a secretory protein. Following infection of Sf9 insect cells with the recombinant baculovirus, the culture supernatant was analyzed by enzyme-linked immunosorbent assay using antigen-coated microplates and either an anti-mouse IgG or an anti-gp64 antibody. A relatively strong signal was obtained in each case, showing antigen-binding activity in the culture supernatant. In western blot analysis of the culture supernatant using the anti-gp64 antibody, specific protein bands were detected at an electrophoretic mobility that coincided with the molecular weight of the Hc-gp64 fusion protein as well as that of gp64. Flow cytometry using a fluorescein isothiocyanate-conjugated antibody specific to mouse IgG successfully detected the Fab fragments on the surface of the Sf9 cells. These results suggest that immunologically functional antibody Fab fragments can be displayed on the surface of baculovirus particles, and that a fluorescence-activated cell sorter with a fluorescence-labeled antigen can isolate baculoviruses displaying specific Fab fragments. This successful baculovirus display of antibody Fab fragments may offer a novel approach for the efficient selection of specific antibodies.

  16. Antigen-Antibody Interaction Database (AgAbDb): a compendium of antigen-antibody interactions.

    Science.gov (United States)

    Kulkarni-Kale, Urmila; Raskar-Renuse, Snehal; Natekar-Kalantre, Girija; Saxena, Smita A

    2014-01-01

    Antigen-Antibody Interaction Database (AgAbDb) is an immunoinformatics resource developed at the Bioinformatics Centre, University of Pune, and is available online at http://bioinfo.net.in/AgAbDb.htm. Antigen-antibody interactions are a special class of protein-protein interactions that are characterized by high affinity and strict specificity of antibodies towards their antigens. Several co-crystal structures of antigen-antibody complexes have been solved and are available in the Protein Data Bank (PDB). AgAbDb is a derived knowledgebase developed with an objective to compile, curate, and analyze determinants of interactions between the respective antigen-antibody molecules. AgAbDb lists not only the residues of binding sites of antigens and antibodies, but also interacting residue pairs. It also helps in the identification of interacting residues and buried residues that constitute antibody-binding sites of protein and peptide antigens. The Antigen-Antibody Interaction Finder (AAIF), a program developed in-house, is used to compile the molecular interactions, viz. van der Waals interactions, salt bridges, and hydrogen bonds. A module for curating water-mediated interactions has also been developed. In addition, various residue-level features, viz. accessible surface area, data on epitope segment, and secondary structural state of binding site residues, are also compiled. Apart from the PDB numbering, Wu-Kabat numbering and explicit definitions of complementarity-determining regions are provided for residues of antibodies. The molecular interactions can be visualized using the program Jmol. AgAbDb can be used as a benchmark dataset to validate algorithms for prediction of B-cell epitopes. It can as well be used to improve accuracy of existing algorithms and to design new algorithms. AgAbDb can also be used to design mimotopes representing antigens as well as aid in designing processes leading to humanization of antibodies. PMID:25048123

  17. Antibody phage display applications for nuclear medicine imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Winthrop, M.D.; Denardo, G.L.; Denardo, S.J. [Sacramento Univ. of California Davis Medical Center, Sacramento, CA (United States). Dept. of Internal Medicine, Div. of Radiodiagnosis and Terapy

    2000-09-01

    Antibody-based constructs genetically engineered from genes of diverse origin provide a remarkable opportunity to develop functional molecular imaging techniques and specific molecular targeted radionuclide therapies. Phage display libraries of antibody fragment genes can be used to select antibody-based constructs that bind any chosen epitope. A large naive human antibody-based library was used to illustrate binding of antibody constructs to a variety of common and unique antigens. Antibody-based libraries from hybridoma cells, lymphocytes from immunized humans or from mice and human antibody repertoires produced in transgenic mice have also been described. Several orders of magnitude of affinity enhancement can be achieved by random or site specific mutations of the selected binding peptide domains of the scFv. Affinities (K{sub d}) as high as 10{sup -}11 M (10 pM) for affinity-matured scFv have been documented. Such gene libraries thus offer an almost limitless variety of antibody-based molecular binding peptide modules that can be used in creative ways for the construction of new targeting agents for functional or molecular imaging and therapy.

  18. Functionally fused antibodies--a novel adjuvant fusion system

    DEFF Research Database (Denmark)

    Larsen, Martin; Jensen, Kim Bak; Christensen, Peter Astrup;

    2008-01-01

    Antibodies capable of recognizing key molecular targets isolated e.g. by phage display technology have been used in the pursuit of new and improved therapies for prevalent human diseases. These approaches often take advantage of non-immunogenic antibody fragments to achieve specific toxin-, radio...

  19. Adult attachment processes: individual and couple perspectives.

    Science.gov (United States)

    Bartholomew, K

    1997-09-01

    This paper overviews a new approach to understanding the range of difficulties experienced in close attachment relationships in adulthood. Drawing on the work of Bowlby, four prototypic adult attachment patterns are defined in terms of the intersection of two underlying dimensions, the positivity of the person's self-image and the positivity of the person's image of others (Bartholomew, 1990; Bartholomew & Horowitz, 1991). The distinct interpersonal difficulties associated with each attachment pattern are described. Findings are presented indicating that individual differences in attachment have implications for the quality of adults' romantic relationships, and that attachment theory may be helpful in understanding violent spousal relationships. Five current issues in the study of adult attachment are addressed: the stability of attachment patterns, the associations between attachment and general personality factors, the relative merits of categorical and prototype assessments of attachment, the identification of multiple attachments in adulthood, and the specificity of adult attachment patterns. It is suggested that the four-category model of adult attachment is especially sensitive to the range and complexity of attachment-related difficulties experienced in adulthood.

  20. A conserved haem redox and trafficking pathway for cofactor attachment

    OpenAIRE

    Richard-Fogal, Cynthia L; Frawley, Elaine R.; Bonner, Eric R.; Zhu, Huifen; San Francisco, Brian; Kranz, Robert G.

    2009-01-01

    A pathway for cytochrome c maturation (Ccm) in bacteria, archaea and eukaryotes (mitochondria) requires the genes encoding eight membrane proteins (CcmABCDEFGH). The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms. For the first time, we purify pathway complexes with trapped haem to elucidate the molecular mechanisms of haem binding, trafficking and redox control. We discovered an early step i...

  1. Attaching Chuck Keys to Machine Tools

    Science.gov (United States)

    Richardson, V.

    1984-01-01

    Chuck keys attached to portable machine tools by retracting lanyards. Lanyard held taut by recoil caddy attached to tool base. Chuck key available for use when needed and safely secured during operation of tool.

  2. Oxytocin enhances the experience of attachment security

    OpenAIRE

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O’Connor, Mary-Frances; Gundel, Harald

    2009-01-01

    Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the experience of attachment security in humans. Within a 3-week interval 26 healthy male students classified with an insecure attachment pattern were invited twice to an ex...

  3. Attachment Theory, Foster Parents and Diversity Tolerance

    OpenAIRE

    Kenny, Michael; Fleming, Ted

    2009-01-01

    relevance to attachment within the biological and foster family. Yet every foster parent has a childhood attachment history that influences their interpersonal relationships in adulthood. The primary concern of the foster parent and their supports is with the foster child. But as a result the foster parent may distract or block reflection on their own attachment history. This presentation will focus on attachment theory and the adult, with particular reference to the foster parent. The pre...

  4. Development of foster mother-child attachment

    OpenAIRE

    Korhonen, J

    2014-01-01

    The impact of early attachment relationships and child-adult attachment relationships to children’s social and emotional development has been recognised for a long time. Since the pioneering attachment theories of John Bowlby and Mary Ainsworth highlighting the importance of secure child-adult attachments, many other theories from various perspectives have risen to fill in the gaps. These theories are examined with the framework of foster care in mind. In Finland, the primary solution fo...

  5. 21 CFR 872.3165 - Precision attachment.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Precision attachment. 872.3165 Section 872.3165...) MEDICAL DEVICES DENTAL DEVICES Prosthetic Devices § 872.3165 Precision attachment. (a) Identification. A precision attachment or preformed bar is a device made of austenitic alloys or alloys containing 75...

  6. Engineering antibody therapeutics.

    Science.gov (United States)

    Chiu, Mark L; Gilliland, Gary L

    2016-06-01

    The successful introduction of antibody-based protein therapeutics into the arsenal of treatments for patients has within a few decades fostered intense innovation in the production and engineering of antibodies. Reviewed here are the methods currently used to produce antibodies along with how our knowledge of the structural and functional characterization of immunoglobulins has resulted in the engineering of antibodies to produce protein therapeutics with unique properties, both biological and biophysical, that are leading to novel therapeutic approaches. Antibody engineering includes the introduction of the antibody combining site (variable regions) into a host of architectures including bi and multi-specific formats that further impact the therapeutic properties leading to further advantages and successes in patient treatment. PMID:27525816

  7. The Biochemical Properties of Antibodies and Their Fragments.

    Science.gov (United States)

    Hnasko, Robert M

    2015-01-01

    Immunoglobulins (Ig) or antibodies are powerful molecular recognition tools that can be used to identify minute quantities of a given target analyte. Their antigen-binding properties define both the sensitivity and selectivity of an immunoassay. Understanding the biochemical properties of this class of protein will provide users with the knowledge necessary to select the appropriate antibody composition to maximize immunoassay results. Here we define the general biochemical properties of antibodies and their similarities and differences, explain how these properties influence their functional relationship to an antigen target, and describe a method for the enzymatic fragmentation of antibodies into smaller functional parts.

  8. Optimization of AFP-radioimmunoassay using Antibody Capture Technique

    International Nuclear Information System (INIS)

    Alpha-fetoprotein (AFP) is a substance produced by the unborn baby. When the neural tube is not properly formed large amounts of AFP pass into the amniotic fluid and reach the mother's blood. By measuring AFP in the mother's blood and amniotic fluid, it is possible to tell whether or not there is a chance that the unborn baby has a neural tube defect. AFP also used as a tumor marker for hepatocellular carcinoma. There are many different techniques for measuring AFP in blood, but the most accurate one is the immunoassay technique. The immunoassays can be classified on the basis of methodology into three classes; (1) the antibody capture assays, (2) the antigen capture assay, (3)the two-antibody sandwich assays. In this present study, the antibody capture assay in which the antigen is attached to a solid support, and labeled antibody is allowed to bind, will be optimized

  9. Recent advances in the construction of antibody-drug conjugates

    Science.gov (United States)

    Chudasama, Vijay; Maruani, Antoine; Caddick, Stephen

    2016-02-01

    Antibody-drug conjugates (ADCs) comprise antibodies covalently attached to highly potent drugs using a variety of conjugation technologies. As therapeutics, they combine the exquisite specificity of antibodies, enabling discrimination between healthy and diseased tissue, with the cell-killing ability of cytotoxic drugs. This powerful and exciting class of targeted therapy has shown considerable promise in the treatment of various cancers with two US Food and Drug Administration approved ADCs currently on the market (Adcetris and Kadcyla) and approximately 40 currently undergoing clinical evaluation. However, most of these ADCs exist as heterogeneous mixtures, which can result in a narrow therapeutic window and have major pharmacokinetic implications. In order for ADCs to deliver their full potential, sophisticated site-specific conjugation technologies to connect the drug to the antibody are vital. This Perspective discusses the strategies currently used for the site-specific construction of ADCs and appraises their merits and disadvantages.

  10. High affinity human antibody fragments to dengue virus non-structural protein 3.

    Directory of Open Access Journals (Sweden)

    Nicole J Moreland

    Full Text Available BACKGROUND: The enzyme activities catalysed by flavivirus non-structural protein 3 (NS3 are essential for virus replication. They are distributed between the N-terminal protease domain in the first one-third and the C-terminal ATPase/helicase and nucleoside 5' triphosphatase domain which forms the remainder of the 618-aa long protein. METHODOLOGY/PRINCIPAL FINDINGS: In this study, dengue full-length NS3 protein with residues 49 to 66 of NS2B covalently attached via a flexible linker, was used as bait in biopanning with a naïve human Fab phage-display library. Using a range of truncated constructs spanning the NS2B cofactor region and the full-length NS3, 10 unique Fab were identified and characterized. Of these, monoclonal Fab 3F8 was shown to bind α3″ (residues 526 through 531 within subdomain III of the helicase domain. The antibody inhibits the ATPase and helicase activites of NS3 in biochemical assays and reduces DENV replication in HEK293 cells that were previously transfected with Fab 3F8 compared with mock transfected cells. CONCLUSIONS/SIGNIFICANCE: Antibodies such as 3F8 are valuable tools for studying the molecular mechanisms of flaviviral replication and for the monospecific detection of replicating dengue virus in vivo.

  11. RBC Antibody Screen

    Science.gov (United States)

    ... the baby is Rh-positive and the mother's antibody status is negative for anti-D, the mother is given additional RhIG. This test also may be used to help diagnose autoimmune-related hemolytic anemia ... when a person produces antibodies against his or her own RBC antigens. This ...

  12. Selection of Recombinant Human Antibodies.

    Science.gov (United States)

    Tomszak, Florian; Weber, Susanne; Zantow, Jonas; Schirrmann, Thomas; Hust, Michael; Frenzel, André

    2016-01-01

    Since the development of therapeutic antibodies the demand of recombinant human antibodies is steadily increasing. Traditionally, therapeutic antibodies were generated by immunization of rat or mice, the generation of hybridoma clones, cloning of the antibody genes and subsequent humanization and engineering of the lead candidates. In the last few years, techniques were developed that use transgenic animals with a human antibody gene repertoire. Here, modern recombinant DNA technologies can be combined with well established immunization and hybridoma technologies to generate already affinity maturated human antibodies. An alternative are in vitro technologies which enabled the generation of fully human antibodies from antibody gene libraries that even exceed the human antibody repertoire. Specific antibodies can be isolated from these libraries in a very short time and therefore reduce the development time of an antibody drug at a very early stage.In this review, we describe different technologies that are currently used for the in vitro and in vivo generation of human antibodies. PMID:27236551

  13. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... You appear to have an allergic response to insulin Insulin no longer seems to control your diabetes

  14. Protein mimics by attachment of cyclic peptides to molecular scaffolds

    NARCIS (Netherlands)

    van de Langemheen, W.

    2014-01-01

    The interaction between proteins is important in all biological functions. In practically every cellular process protein complexes have been identified as essential components. Defects or disturbance in the regulation of protein-protein interactions are responsible for many diseases. Therefore, the

  15. Attachment theory: A review of research

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2005-01-01

    Full Text Available Research of attachment is numerous and versatile. They differ according to problems addressed, methodology applied (longitudinal studies, studies with horizontal designs, different instruments used, different methods of data analysis, and characteristics of samples involved (concerning age socio/economic status, family ecology. The research is commonly relied on the core assumptions of the theory itself, and the shared characteristic is orientation to explore complex phenomena of human experience and functioning. From the vast variety of research only those who most directly test the basic assumptions of the attachment theory are focused and addressed in the paper: representation of patterns of attachment in the childhood and adulthood, stability and change of attachment security from infancy to early adulthood, transgenerational transmission of attachment characteristics, the place and the role of attachment behavioral system in the personality development. The aim of the paper is to highlight the basic research and theory issues and directions, and illustrate them with concrete research date.

  16. Wear simulation effects on overdenture stud attachments.

    Science.gov (United States)

    Rutkunas, Vygandas; Mizutani, Hiroshi; Takahashi, Hidekazu; Iwasaki, Naohiko

    2011-01-01

    The aim of this study was to evaluate wear effects on overdenture resilient attachments. Six commercially available attachments were investigated: ERA orange and white (EO and EW), Locator pink, white and blue (LRP, LRW and LRB) and OP anchor (OP). Five specimens were used for wear simulation while other two specimens served as controls. Fifteen thousands insertion-removal cycles were simulated. Dimensional changes and surface characteristics were evaluated using light microscopy and SEM, respectively. Sudden decrease of retentive force was characteristic for EO and EW attachments. Retentive force of Locator attachments fluctuated throughout the wear simulation period. Dimensional changes and surface wear was more expressed on plastic cores than on plastic rings of attachment males. Based on SEM analysis, some of the specimens obtained smoother surface after wear simulation. Mechanism of retention loss of resilient overdenture attachments can be only partially explained by dimensional changes and surface alterations.

  17. Association Between Insecure Attachment and ADHD

    DEFF Research Database (Denmark)

    Storebo, Ole Jakob; Darling Rasmussen, Pernille; Simonsen, Erik

    2016-01-01

    Objective: Psychological theories have postulated an association between insecure attachment and ADHD. The objective of this study is to investigate possible association between insecure attachment and ADHD in children and adults. Method: Review of literature was performed using the Psyc......INFO, Medline, and EMBASE databases. Results: Twenty-nine studies were included in the review. Overall, the studies showed that parental attachment problems and environmental mediating factors were significantly associated with childhood ADHD. Adults with ADHD had a much higher incidence of insecure attachment...... styles than reported in the general population. Conclusion: There seems to be a clear association between ADHD and insecure attachment. It is likely that early intervention in the form of parent training and pharmacological treatment may prevent development of attachment problems. But such studies have...

  18. Ligation of Fc gamma receptor IIB inhibits antibody-dependent enhancement of dengue virus infection.

    Science.gov (United States)

    Chan, Kuan Rong; Zhang, Summer Li-Xin; Tan, Hwee Cheng; Chan, Ying Kai; Chow, Angelia; Lim, Angeline Pei Chiew; Vasudevan, Subhash G; Hanson, Brendon J; Ooi, Eng Eong

    2011-07-26

    The interaction of antibodies, dengue virus (DENV), and monocytes can result in either immunity or enhanced virus infection. These opposing outcomes of dengue antibodies have hampered dengue vaccine development. Recent studies have shown that antibodies neutralize DENV by either preventing virus attachment to cellular receptors or inhibiting viral fusion intracellularly. However, whether the antibody blocks attachment or fusion, the resulting immune complexes are expected to be phagocytosed by Fc gamma receptor (FcγR)-bearing cells and cleared from circulation. This suggests that only antibodies that are able to block fusion intracellularly would be able to neutralize DENV upon FcγR-mediated uptake by monocytes whereas other antibodies would have resulted in enhancement of DENV replication. Using convalescent sera from dengue patients, we observed that neutralization of the homologous serotypes occurred despite FcγR-mediated uptake. However, FcγR-mediated uptake appeared to be inhibited when neutralized heterologous DENV serotypes were used instead. We demonstrate that this inhibition occurred through the formation of viral aggregates by antibodies in a concentration-dependent manner. Aggregation of viruses enabled antibodies to cross-link the inhibitory FcγRIIB, which is expressed at low levels but which inhibits FcγR-mediated phagocytosis and hence prevents antibody-dependent enhancement of DENV infection in monocytes. PMID:21746897

  19. Rate coefficients for dissociative attachment and resonant electron-impact dissociation involving vibrationally excited O{sub 2} molecules

    Energy Technology Data Exchange (ETDEWEB)

    Laporta, V. [Istituto di Metodologie Inorganiche e dei Plasmi, CNR, Bari, Italy and Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom); Celiberto, R. [Dipartimento di Ingegneria Civile, Ambientale, del Territorio, Edile e di Chimica, Politecnico di Bari, Italy and Istituto di Metodologie Inorganiche e dei Plasmi, CNR, Bari (Italy); Tennyson, J. [Department of Physics and Astronomy, University College London, London WC1E 6BT (United Kingdom)

    2014-12-09

    Rate coefficients for dissociative electron attachment and electron-impact dissociation processes, involving vibrationally excited molecular oxygen, are presented. Analytical fits of the calculated numerical data, useful in the applications, are also provided.

  20. Emergence of tempered preferential attachment from optimization

    OpenAIRE

    D'Souza, Raissa M.; Borgs, Christian; Chayes, Jennifer T.; Berger, Noam; Kleinberg, Robert D.

    2007-01-01

    We show how preferential attachment can emerge in an optimization framework, resolving a long-standing theoretical controversy. We also show that the preferential attachment model so obtained has two novel features, saturation and viability, which have natural interpretations in the underlying network and lead to a power-law degree distribution with exponential cutoff. Moreover, we consider a generalized version of this preferential attachment model with independent saturation and viability, ...

  1. Explaining gender differences in preschoolers’ attachment style

    OpenAIRE

    Tønnessen, Ellen

    2014-01-01

    Gender has throughout most attachment literature not been considered an important factor in the development of individual differences in attachment. However, some studies on preschoolers, especially using story completion/narrative measures of attachment representations, have found prominent gender differences. The present study aims to replicate such gender differences, and to examine possible explanatory variables. This will be done by using a large community sample of preschoolers from Nor...

  2. Positron-molecule interactions: resonant attachment, annihilation, and bound states

    CERN Document Server

    Gribakin, G F; Surko, C M; 10.1103/RevModPhys.82.2557

    2010-01-01

    This article presents an overview of current understanding of the interaction of low-energy positrons with molecules with emphasis on resonances, positron attachment and annihilation. Annihilation rates measured as a function of positron energy reveal the presence of vibrational Feshbach resonances (VFR) for many polyatomic molecules. These resonances lead to strong enhancement of the annihilation rates. They also provide evidence that positrons bind to many molecular species. A quantitative theory of VFR-mediated attachment to small molecules is presented. It is tested successfully for selected molecules (e.g., methyl halides and methanol) where all modes couple to the positron continuum. Combination and overtone resonances are observed and their role is elucidated. In larger molecules, annihilation rates from VFR far exceed those explicable on the basis of single-mode resonances. These enhancements increase rapidly with the number of vibrational degrees of freedom. While the details are as yet unclear, intr...

  3. Crystallization by Particle Attachment in Synthetic, Biogenic, and Geologic Environments

    Energy Technology Data Exchange (ETDEWEB)

    De Yoreo, James J.; Gilbert, Pupa U.; Sommerdijk, Nico; Penn, R. Lee; Whitelam, Stephen B.; Joester, Derk; Zhang, Hengzhong; Rimer, Jeffrey D.; Navrotsky, Alexandra; Banfield, Jillian F.; Wallace, Adam F.; Michel, F. M.; Meldrum, Fiona C.; Colfen, Helmut; Dove, Patricia M.

    2015-07-31

    Field and laboratory observations show that crystals commonly form by the addition and attachment of particles that range from multi-ion complexes to fully formed nanoparticles. These non-classical pathways to crystallization are diverse, in contrast to classical models that consider the addition of monomeric chemical species. We review progress toward understanding crystal growth by particle attachment processes and show that multiple pathways result from the interplay of free energy landscapes and reaction dynamics. Much remains unknown about the fundamental aspects; particularly the relationships between solution structure, interfacial forces, and particle motion. Developing a predictive description that connects molecular details to ensemble behavior will require revisiting long-standing interpretations of crystal formation in synthetic systems and patterns of mineralization in natural environments.

  4. A conserved haem redox and trafficking pathway for cofactor attachment

    Science.gov (United States)

    Richard-Fogal, Cynthia L; Frawley, Elaine R; Bonner, Eric R; Zhu, Huifen; San Francisco, Brian; Kranz, Robert G

    2009-01-01

    A pathway for cytochrome c maturation (Ccm) in bacteria, archaea and eukaryotes (mitochondria) requires the genes encoding eight membrane proteins (CcmABCDEFGH). The CcmABCDE proteins are proposed to traffic haem to the cytochrome c synthetase (CcmF/H) for covalent attachment to cytochrome c by unknown mechanisms. For the first time, we purify pathway complexes with trapped haem to elucidate the molecular mechanisms of haem binding, trafficking and redox control. We discovered an early step in trafficking that involves oxidation of haem (to Fe3+), yet the final attachment requires reduced haem (Fe2+). Surprisingly, CcmF is a cytochrome b with a haem never before realized, and in vitro, CcmF functions as a quinol:haem oxidoreductase. Thus, this ancient pathway has conserved and orchestrated mechanisms for trafficking, storing and reducing haem, which assure its use for cytochrome c synthesis even in limiting haem (iron) environments and reducing haem in oxidizing environments. PMID:19629033

  5. Attachment theory: Old and new approach

    Directory of Open Access Journals (Sweden)

    Polovina Nada

    2005-01-01

    Full Text Available The article is an attempt to present holistically the key concepts of attachment theory rediscovered for its potentials. The presented concepts include: narrow definition of attachment, behavioral control system of attachment, attachment working model and patterns of attachment. The concepts are presented in the context of child attachment theory and adult attachment theory, in addition to description of the development of attachment. Concepts, as well as developmental processes are presented from the stand point of pioneers in this field (John Bowlby and Mary Ainsworth as well as from the standpoint of their successors (Everett Waters and Malcolm West. Compacted ness of the theory, possibilities for operationalization of its key concepts and its application to empirical studies of complex psychological issues that have never been scientifically explored, makes it a very prospective theory in view of possible integration of existing research findings and initiating new research and new practices in psychotherapy, social work and work in schools. The goal of this integral presentation of attachment theory is to highlight its benefits and possibilities for understanding and research complex field of human's psychosocial functioning.

  6. Oxytocin enhances the experience of attachment security

    Science.gov (United States)

    Buchheim, Anna; Heinrichs, Markus; George, Carol; Pokorny, Dan; Koops, Eva; Henningsen, Peter; O’Connor, Mary-Frances; Gundel, Harald

    2011-01-01

    Summary Repeated interactions between infant and caregiver result in either secure or insecure relationship attachment patterns, and insecure attachment may affect individual emotion-regulation and health. Given that oxytocin enhances social approach behavior in animals and humans, we hypothesized that oxytocin might also promote the experience of attachment security in humans. Within a 3-week interval 26 healthy male students classified with an insecure attachment pattern were invited twice to an experimental session. Within each session, a single dose of oxytocin or placebo was administered, using a double-blind, placebo-controlled within-subject design. In both conditions, subjects completed an attachment task based on the Adult Attachment Projective Picture System (AAP). Thirty-two AAP picture system presentations depicted attachment-related events (e.g. illness, solitude, separation, loss), and were each accompanied by four prototypical phrases representing one secure and three insecure attachment categories. In the oxytocin condition, a significant proportion of these insecure subjects (N = 18; 69%) changed their rankings of “secure attachment” phrases towards the more appropriate for the AAP picture presentation, and the same subjects decreased in overall rating of the “insecure attachment” phrases. In particular, there was a significant decrease in the number of subjects ranking the pictures with “insecure-preoccupied” phrases from the placebo to the oxytocin condition. We find that a single dose of intranasally administered oxytocin is sufficient to induce a significant increase in the experience of attachment security in adults classified previously as insecure. PMID:19457618

  7. Sine-Bar Attachment For Machine Tools

    Science.gov (United States)

    Mann, Franklin D.

    1988-01-01

    Sine-bar attachment for collets, spindles, and chucks helps machinists set up quickly for precise angular cuts that require greater precision than provided by graduations of machine tools. Machinist uses attachment to index head, carriage of milling machine or lathe relative to table or turning axis of tool. Attachment accurate to 1 minute or arc depending on length of sine bar and precision of gauge blocks in setup. Attachment installs quickly and easily on almost any type of lathe or mill. Requires no special clamps or fixtures, and eliminates many trial-and-error measurements. More stable than improvised setups and not jarred out of position readily.

  8. Attachment fixation of the overdenture: part II.

    Science.gov (United States)

    Mensor, M C

    1978-01-01

    Many attachment systems of the bar or stud type increase the stability of an overdenture. When selecting an attachment it is essential to consider the skill of the dentist-laboratory team as well as the dexterity of the patient and to use the easiest system that will still improve stabilization. Generally simplicity in design, ease of maintenance, and minimum leverage should be paramount considerations in selection. Use of a guide such as the EM Gauge and of the EM Attachment Selector significantly reduces the confusion in selecting attachments and increases the working armamentarium for stabilizing an overdenture. PMID:340660

  9. Overdenture locator attachments for atrophic mandible.

    Science.gov (United States)

    Mahajan, Neerja; Thakkur, Rahul K

    2013-10-01

    Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40° of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  10. Overdenture locator attachments for atrophic mandible

    Directory of Open Access Journals (Sweden)

    Neerja Mahajan

    2013-01-01

    Full Text Available Implant-supported overdentures provide a good opportunity for dentists to improve oral health and quality-of-life of patients. Atrophic mandible poses a significant challenge to successful oral rehabilitation with dental implants. In this article, the fabrication of lower overdenture by two narrow platform implants is described with dual retentive, resilient, self-locating locator attachment system. The locator attachment system has the lowest profile in comparison with the ball and bar attachments and is versatile up to 40΀ of divergence between two implants. By using locators as attachments, we can meet functional, economic and social expectation of patients with ease and satisfaction.

  11. Attachment to an endogenous laminin-like protein initiates sprouting by leech neurons

    OpenAIRE

    1988-01-01

    Leech neurons in culture sprout rapidly when attached to extracts from connective tissue surrounding the nervous system. Laminin-like molecules that promote sprouting have now been isolated from this extracellular matrix. Two mAbs have been prepared that react on immunoblots with a approximately equal to 220- and a approximately equal to 340-kD polypeptide, respectively. These antibodies have been used to purify molecules with cross-shaped structures in the electron microscope. The molecules,...

  12. Adhesion of Photon-Driven Molecular Motors to Surfaces via 1,3-Dipolar Cycloadditions : Effect of Interfacial Interactions on Molecular Motion

    NARCIS (Netherlands)

    Carroll, Gregory T.; London, Gabor; Fernández Landaluce, Tatiana; Rudolf, Petra; Feringa, Ben L.

    2011-01-01

    We report the attachment of altitudinal light-driven molecular motors to surfaces using 1,3-dipolar cycloaddition reactions. Molecular motors were designed containing azide or alkyne groups for attachment to alkyne- or azide-modified surfaces. Surface attachment was characterized by UV-vis, IR, XPS,

  13. Biliprotein maturation: the chromophore attachment.

    Science.gov (United States)

    Scheer, H; Zhao, K-H

    2008-04-01

    Biliproteins are a widespread group of brilliantly coloured photoreceptors characterized by linear tetrapyrrolic chromophores, bilins, which are covalently bound to the apoproteins via relatively stable thioether bonds. Covalent binding stabilizes the chromoproteins and is mandatory for phycobilisome assembly; and, it is also important in biliprotein applications such as fluorescence labelling. Covalent binding has, on the other hand, also considerably hindered biliprotein research because autocatalytic chromophore additions are rare, and information on enzymatic addition by lyases was limited to a single example, an EF-type lyase attaching phycocyanobilin to cysteine-alpha84 of C-phycocyanin. The discovery of new activities for the latter lyases, and of new types of lyases, have reinvigorated research activities in the subject. So far, work has mainly concentrated on cyanobacterial phycobiliproteins. Methodological advances in the process, however, as well as the finding of often large numbers of homologues, opens new possibilities for research on the subsequent assembly/disassembly of the phycobilisome in cyanobacteria and red algae, on the assembly and organization of the cryptophyte light-harvesting system, on applications in basic research such as protein folding, and on the use of phycobiliproteins for labelling.

  14. Coexistence in preferential attachment networks

    CERN Document Server

    Antunović, Tonći; Racz, Miklos Z

    2013-01-01

    Competition in markets is ubiquitous: cell-phone providers, computer manufacturers, and sport gear brands all vie for customers. Though several coexisting competitors are often observed in empirical data, many current theoretical models of competition on small-world networks predict a single winner taking over the majority of the network. We introduce a new model of product adoption that focuses on word-of-mouth recommendations to provide an explanation for this coexistence of competitors. The key property of our model is that customer choices evolve simultaneously with the network of customers. When a new node joins the network, it chooses neighbors according to preferential attachment, and then chooses its type based on the number of initial neighbors of each type. This can model a new cell-phone user choosing a cell-phone provider, a new student choosing a laptop, or a new athletic team member choosing a gear provider. We provide a detailed analysis of the new model; in particular, we determine the possibl...

  15. Hamiltonian dynamics of preferential attachment

    International Nuclear Information System (INIS)

    Prediction and control of network dynamics are grand-challenge problems in network science. The lack of understanding of fundamental laws driving the dynamics of networks is among the reasons why many practical problems of great significance remain unsolved for decades. Here we study the dynamics of networks evolving according to preferential attachment (PA), known to approximate well the large-scale growth dynamics of a variety of real networks. We show that this dynamics is Hamiltonian, thus casting the study of complex networks dynamics to the powerful canonical formalism, in which the time evolution of a dynamical system is described by Hamilton’s equations. We derive the explicit form of the Hamiltonian that governs network growth in PA. This Hamiltonian turns out to be nearly identical to graph energy in the configuration model, which shows that the ensemble of random graphs generated by PA is nearly identical to the ensemble of random graphs with scale-free degree distributions. In other words, PA generates nothing but random graphs with power-law degree distribution. The extension of the developed canonical formalism for network analysis to richer geometric network models with non-degenerate groups of symmetries may eventually lead to a system of equations describing network dynamics at small scales. (paper)

  16. HIV Antibody Test

    Science.gov (United States)

    ... be limited. Home Visit Global Sites Search Help? HIV Antibody and HIV Antigen (p24) Share this page: Was this page helpful? Also known as: HIV Screening Tests; AIDS Test; AIDS Screen; HIV Serology; ...

  17. Antinuclear antibody panel

    Science.gov (United States)

    ... blood may be due to: Chronic liver disease Collagen vascular disease Drug-induced lupus erythematosus Myositis (inflammatory muscle disease) ... Saunders; 2011:chap 51. Read More Antibody Arthritis Collagen vascular disease Drug-induced lupus erythematosus Liver disease Scleroderma Systemic ...

  18. Anti-cartilage antibody.

    Science.gov (United States)

    Greenbury, C L; Skingle, J

    1979-08-01

    Antibody to cartilage has been demonstrated by indirect immunofluorescence on rat trachea in the serum of about 3% of 1126 patients with rheumatoid arthritis. Titres ranged from 1:20 to 1:640. The antibody was not found in 284 patients with primary or secondary osteoarthritis or in 1825 blood donors, nor, with the exception of two weak reactors, in 1314 paraplegic patients. In most cases the antibody appears to be specific for native type II collagen. Using this as an antigen in a haemagglutination test 94% of anti-cartilage sera were positive, whereas among 100 rheumatoid control sera there were only three weak positives. More than 80% of patients with antibody had some erosion of articular cartilage, but there was no correlation with age, sex, duration of disease, nor any recognisable clinical event or change.

  19. 普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产疗效的Meta分析%Meta analysis of the efficacy of common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion

    Institute of Scientific and Technical Information of China (English)

    杨晶晶; 刘帅斌; 胡丽娜

    2015-01-01

    目的:探讨普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产的疗效。方法:采用Cochrane协作网系统评价方法,对有关普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产研究进行质量评价。结果:低分子肝素组的胎儿流产风险是普通肝素组的0.59倍;低分子肝素组治疗复发性流产妇女最终导致其并发症的发生风险是普通肝素组的1.34倍,但差异均无统计学意义(P>0.05)。结论:普通肝素与低分子肝素治疗抗磷脂抗体阳性复发性流产的临床疗效无差异。%Objective:To investigate the efficacy of common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion.Methods:We adopted the cochrane cooperative network system evaluation method,to do the quality evaluation of the common heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent spontaneous abortion.Results:Low molecular heparin group fetal risk of miscarriage is unfractionated heparin group 0.59 times;low molecular weight heparin group treatment of women with recurrent spontaneous abortion ultimately lead to the complication risk is unfractionated heparin group of 1.34 times,but the difference was not statistically significant (P>0.05).Conclusion:There is no difference between the clinical efficacy of ordinary heparin and low molecular heparin in the treatment of anti phospholipid antibody positive recurrent miscarriage.

  20. Measuring Patients’ Attachment Avoidance in Psychotherapy: Development of the Attachment Avoidance in Therapy Scale (AATS

    Directory of Open Access Journals (Sweden)

    András Láng

    2012-11-01

    Full Text Available A new scale measuring patient-therapist attachment avoidance was developed. Attachment Avoidance in Therapy Scale is a new measure based on the Bartholomew model of adult attachment (Bartholomew & Horowitz, 1991 and the Experience in Close Relationships Scale (Brennan, Clark, & Shaver, 1998 to measure patients’ attachment avoidance towards therapists. With 112 patient-therapist dyads participating in the study, validation of a preliminary scale – measuring both attachment anxiety and attachment avoidance in therapy – took place using therapists’ evaluations of patients’ relational behavior and patients’ self-reports about their attitude toward psychotherapy. Analysis of the data revealed six underlying scales. Results showed all six scales to be reliable. Validation of scales measuring attachment anxiety failed. The importance of Attachment Avoidance in Therapy Scale and its subscales is discussed.

  1. Adaptive responses to antibody based therapy.

    Science.gov (United States)

    Rodems, Tamara S; Iida, Mari; Brand, Toni M; Pearson, Hannah E; Orbuch, Rachel A; Flanigan, Bailey G; Wheeler, Deric L

    2016-02-01

    Receptor tyrosine kinases (RTKs) represent a large class of protein kinases that span the cellular membrane. There are 58 human RTKs identified which are grouped into 20 distinct families based upon their ligand binding, sequence homology and structure. They are controlled by ligand binding which activates intrinsic tyrosine-kinase activity. This activity leads to the phosphorylation of distinct tyrosines on the cytoplasmic tail, leading to the activation of cell signaling cascades. These signaling cascades ultimately regulate cellular proliferation, apoptosis, migration, survival and homeostasis of the cell. The vast majority of RTKs have been directly tied to the etiology and progression of cancer. Thus, using antibodies to target RTKs as a cancer therapeutic strategy has been intensely pursued. Although antibodies against the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) have shown promise in the clinical arena, the development of both intrinsic and acquired resistance to antibody-based therapies is now well appreciated. In this review we provide an overview of the RTK family, the biology of EGFR and HER2, as well as an in-depth review of the adaptive responses undertaken by cells in response to antibody based therapies directed against these receptors. A greater understanding of these mechanisms and their relevance in human models will lead to molecular insights in overcoming and circumventing resistance to antibody based therapy. PMID:26808665

  2. Antibody tumor penetration

    Science.gov (United States)

    Thurber, Greg M.; Schmidt, Michael M.; Wittrup, K. Dane

    2009-01-01

    Antibodies have proven to be effective agents in cancer imaging and therapy. One of the major challenges still facing the field is the heterogeneous distribution of these agents in tumors when administered systemically. Large regions of untargeted cells can therefore escape therapy and potentially select for more resistant cells. We present here a summary of theoretical and experimental approaches to analyze and improve antibody penetration in tumor tissue. PMID:18541331

  3. Expression of Recombinant Antibodies

    OpenAIRE

    Frenzel, André; Hust, Michael; Schirrmann, Thomas

    2013-01-01

    Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transg...

  4. Antibody Prophylaxis and Therapy against Nipah Virus Infection in Hamsters

    OpenAIRE

    Guillaume, V; Contamin, H.; Loth, P.; Grosjean, I.; Courbot, M. C. Georges; Deubel, V.; Buckland, R; Wild, T F

    2006-01-01

    Nipah virus (NiV), a member of the Paramyxoviridae family, causes a zoonotic infection in which the reservoir, the fruit bat, may pass the infection to pigs and eventually to humans. In humans, the infection leads to encephalitis with >40 to 70% mortality. We have previously shown that polyclonal antibody directed to either one of two glycoproteins, G (attachment protein) or F (fusion protein), can protect hamsters from a lethal infection. In the present study, we have developed monoclonal an...

  5. DNA-templated antibody conjugation for targeted drug delivery to cancer cells

    DEFF Research Database (Denmark)

    Liu, Tianqiang

    2016-01-01

    Monoclonal antibodies have been used for the treatment of cancer because of their specificity to tumor markers. However, intact unmodified antibodies used as single agent therapeutics sometimes are not curative. To overcome this, there is a trend to empower them with bioactive payloads (toxins......, chemotherapeutics, radionuclides, cytokines) by means of antibody conjugation. Conventional chemical modification techniques for the conjugation of antibodies result in highly heterogeneous mixtures. This heterogeneity is far from optimal since for therapeutic purpose antibody conjugates are better in homogeneous...... conjugation strategy. Recently, a site-selective antibody conjugation method called “DNA-templated protein conjugation (DTPC)” was developed by our group. The site-selective covalently attachment of single-stranded DNA (ssDNA) to proteins was achieved by using a metal-affinity DNA probe and DNA...

  6. An Attachment Model of University Connectedness

    Science.gov (United States)

    Wilson, Steffen; Gore, Jonathan

    2013-01-01

    Students with high levels of connectedness to the university have been found to be more likely to complete their college degree than are students with low levels of university connectedness. This study examined the role of parental and peer attachment as distal predictors of school connectedness. As predicted, it was found that attachment style to…

  7. An Attachment Perspective on Anger among Adolescents

    Science.gov (United States)

    Konishi, Chiaki; Hymel, Shelley

    2014-01-01

    Extending John Bowlby's hypothesis that dysfunctional anger is a predictable outcome of insecure attachments to parents, this study investigated the relationship between current parent-adolescent attachment and both the experience and expression of anger. Participants included 776 students (379 boys and 397 girls) in grades 8-12. As predicted…

  8. Attachment, emotion regulation and adult crying

    NARCIS (Netherlands)

    Maas, J.; Laan, A.; Vingerhoets, A.J.J.M.

    2011-01-01

    Attachment serves to facilitate the contact with and proximity to the primary caregiver, in that way contributing to a safe exploration of the environment. However, due to inconsistencies in the reaction of the caregiver or her/his absence, insecure attachment styles may develop. This chapter summar

  9. Attachment of Salmonella spp. to pork meat

    DEFF Research Database (Denmark)

    Hansen, Trine; Riber, Leise; Löfström, Charlotta;

    2011-01-01

    Five strains of Salmonella, one wildtype and four knock-out mutants (the prg, flhDC, yhjH and fliC genes) were investigated based on their probability to attach and subsequently detach from a surface of pork fillet. The attachment followed by detachment was measured and modelled for two different...

  10. Attachment and Socioemotional Problems in Middle Childhood

    Science.gov (United States)

    Moss, Ellen; Lecompte, Vanessa

    2015-01-01

    In this article, we will evaluate the evidence concerning links between attachment and behavior problems in the middle childhood period. We will first provide a general introduction to the question of attachment and maladaptation in the middle childhood period, and then examine the recent empirical evidence with respect to both externalizing and…

  11. Romantic adult attachment and basic personality structure

    Directory of Open Access Journals (Sweden)

    Jelena Zeleskov Djoric

    2012-03-01

    Full Text Available The main goal of this study was localization of attachment dimensions in the space described by basic personality traits. Study purported to examine relations between attachment and basic personality structure, in a sample of 203 respondents. Romantic adult attachment was measured by the Experience in Close Relationship Scale, basic personality structure was assessed by the NEO-PI-R personality inventory, and Disintegration, which represents operationalization of Schizotypy as a basic personality trait, was estimated by the Delta 10 test. The results of Principal component analysis showed that attachment dimensions are not separate constructs in relation to basic personality traits. Furthermore, results indicate that attachment dimensions represent emotional dysregulation in close interpersonal relationships, because positive correlations are found between dimensions of Attachment and Mania (.35, Anxiety (.51 and Depression (.55. Negative correlations have been obtained between Attachment and Positive emotions (-.34 and Feelings (-.31. These results suggest that Attachment dimensions should be considered as an expression of basic personality traits in romantic adult's relationships.

  12. Attachment and Dependency in Developmental Perspective.

    Science.gov (United States)

    Sroufe, L. Alan; And Others

    1983-01-01

    Distinguishes between attachment (the relationship between infant and caregiver) and dependency (the reliance of the child on adults for nurturance, attention, or assistance). Assesses preschool children with varying attachment histories and suggests that the roots of overdependency lie in the quality of the early infant-caregiver relationship.…

  13. Attachment Theory Applied to Juvenile Sex Offending.

    Science.gov (United States)

    Goodrow, Kenneth K.; Lim, Mee-Gaik

    1998-01-01

    Attachment theory is applied to identify systemic patterns encouraging juveniles to commit sexual offenses. The role of the helping system in perpetuating offenses is reviewed. The priority of family integrity and the role of professionals in breaking cycles of abuse and repairing earlier destructive emotional attachments are discussed. (EMK)

  14. Attachment Parenting: A Style That Works.

    Science.gov (United States)

    Sears, William

    1995-01-01

    Discusses the benefits of attachment parenting, which emphasizes parental commitment, a low-stress pregnancy, childbirth preparation, breast-feeding with child-led weaning, prompt response to the baby's crying, flexible sleeping arrangements, close-knit father-mother-baby functioning, and the avoidance of detachment parenting. Attachment parenting…

  15. Anxiety, cortisol, and attachment predict plasma oxytocin

    NARCIS (Netherlands)

    Tops, Mattie; Van Peer, Jacobien M.; Korf, Jakob; Wijers, Albertus A.; Tucker, Don M.

    2007-01-01

    Oxytocin and attachment seem to interact in suppressing subjective anxiety and physiological stress responses. In this study we investigated the relationships between individual differences in trait attachment scores, state and trait anxiety, plasma cortisol, and plasma oxytocin levels in healthy pr

  16. Forgiveness and health: The role of attachment

    NARCIS (Netherlands)

    Lawler-Row, K.A.; Hyatt-Edwards, L.; Wünsch, K.L.; Karremans, J.C.T.M.

    2011-01-01

    Attachment was examined for its association to forgiveness and health. Young adults were interviewed about a time of conflict with a parent; during rest and interview periods, readings of blood pressure and heart rate were taken. Participants completed surveys of forgiveness, attachment, relationshi

  17. Adolescent Self-Esteem, Attachment and Loneliness

    Science.gov (United States)

    Dhal, Anubha; Bhatia, Sangeeta; Sharma, Vidhi; Gupta, Priyanka

    2007-01-01

    Objectives: To assess self-esteem, loneliness and attachment styles among adolescents and examine their association with each other and with age and gender. Method: Adolescents (55 males and 55 females) from a public school in Delhi, aged 10-13 years were administered Coopersmith Self-Esteem Inventory (School Form), Attachment Scale and UCLA…

  18. Genetic and Environmental Influences on Adolescent Attachment

    Science.gov (United States)

    Fearon, Pasco; Shmueli-Goetz, Yael; Viding, Essi; Fonagy, Peter; Plomin, Robert

    2014-01-01

    Background: Twin studies consistently point to limited genetic influence on attachment security in the infancy period, but no study has examined whether this remains the case in later development. This study presents the findings from a twin study examining the relative importance of genetic and environmental influences on attachment in…

  19. Antibody informatics for drug discovery

    DEFF Research Database (Denmark)

    Shirai, Hiroki; Prades, Catherine; Vita, Randi;

    2014-01-01

    for antibody rational design using computational approaches to affinity and stability improvement, as well as ab-initio and homology-based antibody modeling; (ii) resources for antibody sequences, structures, and immune epitopes and open drug discovery resources for development of antibody drugs; and (iii...

  20. Adult Attachment, Culturally Adjusted Attachment, and Interpersonal Difficulties of Taiwanese Adults

    Science.gov (United States)

    Wang, Chia-Chih DC; Scalise, Dominick A.

    2010-01-01

    This study examines the applicability of Western adult attachment perspectives to interpersonal difficulties experienced by individuals with indigenous Chinese cultural backgrounds. A total of 275 Taiwanese university students completed self-report surveys of adult attachment, ideal attachment, and interpersonal problems. Culturally adjusted…

  1. Attachment and children's biased attentional processing: evidence for the exclusion of attachment-related information.

    Directory of Open Access Journals (Sweden)

    Eva Vandevivere

    Full Text Available Research in both infants and adults demonstrated that attachment expectations are associated with the attentional processing of attachment-related information. However, this research suffered from methodological issues and has not been validated across ages. Employing a more ecologically valid paradigm to measure attentional processes by virtue of eye tracking, the current study tested the defensive exclusion hypothesis in late childhood. According to this hypothesis, insecurely attached children are assumed to defensively exclude attachment-related information. We hypothesized that securely attached children process attachment- related neutral and emotional information in a more open manner compared to insecurely attached children. Sixty-two children (59.7% girls, 8-12 years completed two different tasks, while eye movements were recorded: task one presented an array of neutral faces including mother and unfamiliar women and task two presented the same with happy and angry faces. Results indicated that more securely attached children looked longer at mother's face regardless of the emotional expression. Also, they tend to have more maintained attention to mother's neutral face. Furthermore, more attachment avoidance was related to a reduced total viewing time of mother's neutral, happy, and angry face. Attachment anxiety was not consistently related to the processing of mother's face. Findings support the theoretical assumption that securely attached children have an open manner of processing all attachment-related information.

  2. Lipophosphoglycan blocks attachment of Leishmania major amastigotes to macrophages.

    Science.gov (United States)

    Kelleher, M; Moody, S F; Mirabile, P; Osborn, A H; Bacic, A; Handman, E

    1995-01-01

    Promastigotes of the intracellular protozoan parasite Leishmania major invade mononuclear phagocytes by a direct interaction between the cell surface lipophosphoglycan found on all Leishmania species and macrophage receptors. This interaction is mediated by phosphoglycan repeats containing oligomers of beta (1-3)Gal residues specific to L. major. We show here that although amastigotes also use lipophosphoglycan to bind to both primary macrophages and a cell line, this interaction is independent of the beta (1-3)Gal residues employed by promastigotes. Binding of amastigotes to macrophages could be blocked by intact lipophosphoglycan from L. major amastigotes as well as by lipophosphoglycan from promastigotes of several other Leishmania species, suggesting involvement of a conserved domain. Binding of amastigotes to macrophages could be blocked significantly by the monoclonal antibody WIC 108.3, directed to the lipophosphoglycan backbone. The glycan core of lipophosphoglycan could also inhibit attachment of amastigotes, but to a considerably lesser extent. The glycan core structure is also present in the type 2 glycoinositolphospholipids which are expressed on the surface of amastigotes at 100-fold-higher levels than lipophosphoglycan. However, their inhibitory effect could not be increased even when they were used at a 300-fold-higher concentration than lipophosphoglycan, indicating that lipophosphoglycan is the major macrophage-binding molecule on amastigotes of L. major. In the presence of complement, the attachment of amastigotes to macrophages was not altered, suggesting that lipophosphoglycan interacts directly with macrophage receptors. PMID:7806383

  3. Feature Selection Approaches In Antibody Display

    OpenAIRE

    Polaka, Inese

    2015-01-01

    Molecular diagnostics tools provide specific data that have high dimensionality due to many factors analyzed in one experiment and few records due to high costs of the experiments. This study addresses the problem of dimensionality in melanoma patient antibody display data by applying data mining feature selection techniques. The article describes feature selection ranking and subset selection approaches and analyzes the performance of various methods evaluating selected feature subsets using...

  4. The Antimicrobial Activity of Porphyrin Attached Polymers

    Science.gov (United States)

    Thompson, Lesley

    2008-03-01

    We are interested in testing the antimicrobial activity of a porphyrin that is attached to a polymer. The porphyrin (5-(4-carboxyphenyl)-10,15,20-tris-(4-pryridyl)) was synthesized from methyl 4-formyl benzoate, 4-pyridinecarboxaldehyde, and pyrrole and attached to a copolymer of polystyrene/poly(vinyl benzyl chloride), which was synthesized by free radical polymerization. The antimicrobial activity of the polymer-attached porphyrin was then determined for gram-negative E. Coli grown to 0.80 OD. In this procedure, glass slides were coated with polymer-attached porphyrin via dip-coating, and the E. Coli bacteria were plated in Luria Broth media. The plates were subsequently exposed to light overnight before they were incubated as porphyrins act as photo-sensitizers when irradiated with light. The polymer-attached porphyrin did exhibit antimicrobial activity and parameters that affect its efficiency will be discussed.

  5. Job Cognition and Justice Influencing Organizational Attachment

    Directory of Open Access Journals (Sweden)

    Sangeeta Sahu

    2014-02-01

    Full Text Available Organizational attachment echoes the psychological bond between employee and employer relations, differing from affective component of commitment in terms of employees’ psychological and behavioral involvement. This study examines the extent to which employee perception about procedural, distributive justice and job cognition contributes toward organizational attachment in India. The effect of justice and job cognition variables relates differently to previous studies from western part of the globe. First, in past studies, procedural justice predicted commitment, whereas, for Indian employees, distributive justice contributed to organizational attachment. Second, the contribution of extrinsic job cognition in organizational attachment was evident in the model developed using Structural Equation Modeling (SEM; AMOS. Organizations must take cognizance of the outcomes exhibited by the behavior of managers while following the laid down policies and processes. Cognition of fairness at workplace and attachment can play key role in limiting retention. Practical implications and future research directions are discussed.

  6. Attachment to groups: theory and measurement.

    Science.gov (United States)

    Smith, E R; Murphy, J; Coats, S

    1999-07-01

    Aspects of people's identification with groups may be understood by borrowing theoretical ideas and measurement strategies from research on attachment in close relationships. People have mental models of the self as a group member and of groups as sources of identity and esteem. These models affect thoughts, emotions, and behaviors related to group membership. Three studies show that two dimensions of attachment to groups, attachment anxiety and avoidance, can be assessed with good reliability, validity, and over-time stability. These factors are distinct from relationship attachment and from other measures of group identification. Group attachment predicts several important outcomes, including emotions concerning the group, time and activities shared with a group, social support, collective self-esteem, and ways of resolving conflict. This conceptualization provides new insights into the nature of people's psychological ties to groups.

  7. Security of attachment and preschool friendships.

    Science.gov (United States)

    Park, K A; Waters, E

    1989-10-01

    Attachment theory proposes that the quality of the mother-child tie predicts the quality of a child's other close relationships. The purpose of this study was to test whether security of attachment to mother is related to the quality of a preschooler's best friendships. 33 4-year-old and their best friends participated (mean age = 46 months). Attachment Q-set data were collected to score security of mother-child attachment. Security data were used to classify the friend pairs as secure-secure or secure-insecure. Best friend dyads were observed for a 1-hour free-play session. Each pair's behavior was described with the Dyadic Relationships Q-set, a measure designed to describe the behavior of a pair of children. Secure-secure pairs were more harmonious, less controlling, more responsive, and happier than secure-insecure pairs. The results are related to previous work on attachment and social competence.

  8. Engineering antibodies for cancer therapy.

    Science.gov (United States)

    Boder, Eric T; Jiang, Wei

    2011-01-01

    The advent of modern antibody engineering has led to numerous successes in the application of these proteins for cancer therapy in the 13 years since the first Food and Drug Administration approval, which has stimulated active interest in developing more and better drugs based on these molecules. A wide range of tools for discovering and engineering antibodies has been brought to bear on this challenge in the past two decades. Here, we summarize mechanisms of monoclonal antibody therapeutic activity, challenges to effective antibody-based treatment, existing technologies for antibody engineering, and current concepts for engineering new antibody formats and antibody alternatives as next generation biopharmaceuticals for cancer treatment.

  9. Traffic of cytoskeletal motors with disordered attachment rates

    Science.gov (United States)

    Grzeschik, H.; Harris, R. J.; Santen, L.

    2010-03-01

    Motivated by experimental results on the interplay between molecular motors and tau proteins, we extend lattice-based models of intracellular transport to include a second species of particle which locally influences the motor-filament attachment rate. We consider various exactly solvable limits of a stochastic multiparticle model before focusing on the low-motor-density regime. Here, an approximate treatment based on the random-walk behavior of single motors gives good quantitative agreement with simulation results for the tau dependence of the motor current. Finally, we discuss the possible physiological implications of our results.

  10. Modification of monoclonal antibodies by polymers possessing chelating properties

    Energy Technology Data Exchange (ETDEWEB)

    Torchilin, V.P.; Khaw, B.A.; Klibanov, A.L.; Slinkin, M.A.; Haber, E.; Smirnov, V.N.

    1986-12-01

    This paper describes a basically new approach to obtaining diagnostic antibodies, consisting of a one-point modification of the antibody, without loss of its activity, by a high-molecular-weight synthetic polymer with the ability of effectively chelating ions of heavy metals. As a result of this approach, preparations of active antibodies containing some tens of atoms of the metal per protein molecule can be obtained. The concentration of radioactive metal (/sup 111/In) was determined with a gamma-counter and the Mn and Cd concentrations by spectroscopy. Gel-filtration of polymer-modified antibodies after binding of /sup 111/InCl/sub 3/ is shown. Also, solid-phase radioimmunoassay of antibodies and Fab fragments, native and modified by chelating polymers, is presented.

  11. Prokaryotic Expression and Polyclonal Antibody Preparation of PRL3

    Institute of Scientific and Technical Information of China (English)

    SHEN Xing-gui; LI Wan-nan; WANG Jing; JIANG Yi-qun; LI Qing-shan; FU Xue-qi

    2007-01-01

    Phosphatase of regenerating liver 3(PRL3), which belongs to the superfamily of protein tyrosine phosphatases (PTPs), represents a group of low molecular weight PTPs that participate in tumorigenesis and metastasis processes.Presented here are the results of cloning, prokaryotic expression, purification, and polyclonal antibody preparation of PRL3. To obtain a specific polyclonal antibody against PRL3, the authors have prepared GST-PRL3 to immunize rabbits and purify an anti-PRL3 polyclonal antibody by negative selection affinity columns. Western blot analysis shows that the anti-PRL3 polyclonal antibody has a specific binding ability with PRL3 protein. The anti-PRL3 polyclonal antibody provides a good tool to further study the function of PRL3.

  12. Production of Bartonella Genus-Specific Monoclonal Antibodies

    OpenAIRE

    Liang, Zhongxing; La Scola, Bernard; Lepidi, Hubert; Raoult, Didier

    2001-01-01

    Monoclonal antibodies (MAbs) which react with heat-resistant proteins with molecular masses of 32 to 33 kDa of 14 different Bartonella species were produced. These antibodies did not react with antigens of 26 diverse bacterial strains by microimmunofluorescence assay except MAb B3D4, which reacted with Chlamydia psittaci and Chlamydia trachomatis at low titers. The identification of a common Bartonella antigenic protein will make it possible to later produce a diagnostic antigen by cloning an...

  13. Longitudinal association between adolescent attachment, adult romantic attachment, and emotion regulation strategies.

    Science.gov (United States)

    Pascuzzo, Katherine; Cyr, Chantal; Moss, Ellen

    2013-01-01

    Attachment security towards parents and peers in adolescence, and romantic attachment styles and emotion regulation strategies in young adulthood, were evaluated using an eight-year longitudinal design. Fifty-six young adults completed the Inventory of Parent and Peer Attachment (IPPA) at age 14, and then, at age 22, the Experience in Close Relationships (ECR) and the Coping Inventory for Stressful Situations (CISS), an emotion regulation questionnaire concerning coping strategies, including task-oriented versus emotion-oriented foci. Results indicated that greater insecurity to parents and peers in adolescence predicted a more anxious romantic attachment style and greater use of emotion-oriented strategies in adulthood. Concurrently, anxious adult attachment style was related to more emotion-oriented strategies, whereas an avoidant attachment style was related to less support-seeking. Analyses also identified emotion-oriented coping strategies as a partial mediator of the link between adolescent attachment insecurity to parents and adult anxious attachment, and a complete mediator of the association between adolescent attachment insecurity to peers and adult anxious attachment. These findings support the core assumption of continuity in attachment theory, where relationships to parents influence close romantic relationships in adulthood.

  14. Slides with no attached paper

    International Nuclear Information System (INIS)

    This document brings together the different presentations (slides) given at the workshop but with no attached paper. These slides refer to the following presentations: - Presentation of ITN (Instituto Tecnologico e Nuclear); - Minor Actinide Partitioning (Dominique Warin); - Transmutation (Janne Wallenius); - Radioactive Waste Management, IGD-TP (Gerald Ouzounian); - Present status of the Swedish nuclear waste management programme (Peter Wikberg); - The U.S. Fuel Cycle Research and Development Program - Separations Research and Development (Terry Todd); - Strategies and national programs of closed fuel cycles - Russian Expert Vision (Mikhael Kormilitsyn) - Extraction Studies Of Potential Solvent Formulations For The GANEX Process (Fiona MacLachlan); - Investigations of The Fundamental Chemistry of the TALSPEAK Process (Ken Nash); - Extraction Separation of Trivalent Minor Actinides and Lanthanides by Hexa-dentate Nitrogen-donor Extractant, TPEN, and its Analogs (Kenji Takeshita); - Fluorinated Diluents for HLW Processing - technological point of view (Vasiliy Babain); - Extraction properties of some new pyridine molecules and search for better diluents (Irena Spendlikova); - Kinetics of extraction of Eu3+ ion by TODGA and CyMe4-BTBP studied using the RMC technique (Trong Hung Vu); - Redox Chemistry of Neptunium in Solutions of Nitric Acid (Alena Paulenova); - NMR applied to actinide ions and their complexes. In search of covalency effects (Geoffrey Vidick); - Towards 'Stability Rules' for Radiolysis of bis-DGA compounds (Ana Nunez); - Pyroprocess Research Activities at IGCAR, Kalpakkam, India (K. Nagarajan); - Critical issues of nuclear energy systems employing molten salt fluorides: from ISTC No. 1606 to No. 3749 (1. year of project activity) and MARS/EVOL cooperation (Victor Ignatiev); - Conversion processes: Internal Gelation and the Sphere-pac concept (Manuel Pouchon); - A Combined Nuclear Technology and Nuclear Chemistry Master. A Unique Initiative

  15. Highly active antibody-modified magnetic polyelectrolyte capsules.

    Science.gov (United States)

    Valdepérez, Daniel; Del Pino, Pablo; Sánchez, Lourdes; Parak, Wolfgang J; Pelaz, Beatriz

    2016-07-15

    Polyelectrolyte hollow capsules are versatile platforms typically used for encapsulation of a wide variety of macromolecules in their cavity. The polymer shell of these capsules as composed by alternating layers of oppositely charged polyelectrolytes also allows for adding additional functionalities. The properties of the shell can be for example engineered by trapping different nanoparticles in-between the shell layers and/or by attaching bioactive molecules such as antibodies to the outermost layer. Herein, iron oxide NPs were inmobilized into the shell of polyelectrolyte capsules and the outermost layer of the shell was covalently modified with anti peroxidase antibodies. These capsules act as prototype model system, aiming to obtain a microstructure with the potential capability to specifically recognize and separate macromolecules. Due to the magnetic nanoparticles in the capsule shell, the capsules together with the attached target might be extracted by magnetic field gradients. Here we verified this approach by extracting horseradish peroxidase from a solution through magnetic separation with capsules bearing antibodies against horseradish peroxidase. The bioactivity of the capsules and the high degree of specific antibody functionalization were confirmed and quantified through an enzymatic reaction mediated by the extracted horseradish peroxidase. PMID:27089014

  16. Improved Detection of Domoic Acid Using Covalently Immobilised Antibody Fragments

    Directory of Open Access Journals (Sweden)

    J. Gerard Wall

    2013-03-01

    Full Text Available Antibody molecules, and antibody fragments in particular, have enormous potential in the development of biosensors for marine monitoring. Conventional immobilisation approaches used in immunoassays typically yield unstable and mostly incorrectly oriented antibodies, however, resulting in reduced detection sensitivities for already low concentration analytes. The 2H12 anti-domoic acid scFv antibody fragment was engineered with cysteine-containing linkers of two different lengths, distal to the antigen binding pocket, for covalent and correctly oriented immobilisation of the scFvs on functionalised solid supports. The Escherichia coli-produced, cysteine-engineered scFvs dimerised in solution and demonstrated similar efficiencies of covalent immobilisation on maleimide-activated plates and minimal non-covalent attachment. The covalently attached scFvs exhibited negligible leaching from the support under acidic conditions that removed almost 50% of the adsorbed wildtype fragment, and IC50s for domoic acid of 270 and 297 ng/mL compared with 1126 and 1482 ng/mL, respectively, for their non-covalently adsorbed counterparts. The expression and immobilisation approach will facilitate the development of stable, reusable biosensors with increased stability and detection sensitivity for marine neurotoxins.

  17. An attachment research perspective on ADHD.

    Science.gov (United States)

    Kissgen, Ruediger; Franke, Sebastian

    2016-06-01

    Since the beginning of clinical attachment research in the mid-1980s the number of research projects in this area has been continuously increasing. The research questions so far can be allocated to numerous medical disciplines such as psychosomatic medicine, adult psychiatry or child and adolescent psychiatry. Recently, children with ADHD and their families have also become subjects of this branch of research. Their specific behavioral characteristics from early childhood on constitute unique challenges on the parent-child interaction. If these interactions develop in a suboptimal way, children may develop an insecure or even a disorganized attachment quality. The latter represents a risk factor for a clinically significant psychopathological development.This article initially presents basic principles of attachment theory and discusses the relevance of the cardinal symptoms of ADHD for clinical attachment research. Subsequently, it outlines and discusses the main results of existing research regarding attachment and ADHD. It concludes with a perspective on research questions that need to be addressed in the future with regard to a transgenerational model that highlights the importance of parental attachment representations to the development of children's attachment quality.

  18. Preschool teacher attachment and attention skills.

    Science.gov (United States)

    Commodari, Elena

    2013-01-01

    Attention underlies and energizes all cognitive and behavioral activities. Many studies showed that the quality of child attachment (both to parental and non parental figures) influences cognitive functions and attention. This study aimed to investigate the relationships among attachment to preschool teachers and attention in a sample of preschoolers. In particular, the study analyzed whether child attachment security to preschool teachers influences the different aspects of their attention skills. In addition, gender- and age-related differences in attention and teacher attachment were explored. Research was conducted using two standardized instruments: the Attention and Concentration Battery, and the Attachment Q Sort. Participants were 279 children (147 male, 132 female) who attended two preschools in a town in Southern Italy. Descriptive analyses, t-tests analyses, and correlation and regression analyses were carried out. Findings highlighted several interesting points concerning the relationships that occur among attachment to preschool teachers and attention. Children with secure attachments presented higher reaction time and better auditory, visual, and visual spatial selectivity and maintenance.

  19. Monoclonal antibodies and Fc fragments for treating solid tumors

    Directory of Open Access Journals (Sweden)

    Eisenbeis AM

    2012-01-01

    Full Text Available Andrea M Eisenbeis, Stefan J GrauDepartment of Neurosurgery, University Hospital of Cologne, Cologne, GermanyAbstract: Advances in biotechnology, better understanding of pathophysiological processes, as well as the identification of an increasing number of molecular markers have facilitated the use of monoclonal antibodies and Fc fragments in various fields in medicine. In this context, a rapidly growing number of these substances have also emerged in the field of oncology. This review will summarize the currently approved monoclonal antibodies used for the treatment of solid tumors with a focus on their clinical application, biological background, and currently ongoing trials.Keywords: targeted therapy, monoclonal antibodies, cancer, biological therapy

  20. The fourth pattern of attachment: Disorganized / disoriented

    Directory of Open Access Journals (Sweden)

    Zlatka Cugmas

    2003-09-01

    Full Text Available On the basis of the study of recent scientific literature about the development of attachment behavior, the author answers the following questions about: the behavior children categorized as Disorganized/disorientated or Controlling in the procedure of the Strange situation; the life circumstances, in which these children live; the reasons for lack of balanced strategies of attachment and characteristics of their general manner of adaptation. The author finds the characteristics of the mothers' (insensitivity to be significantly influential for the emergence of the fourth pattern of attachment. These children are heterogeneous regarding adaptation in general. Professional help preceding negative consequences for their socioemotional development is neccesary.

  1. Understanding the Role of Solvation Forces on the Preferential Attachment of Nanoparticles in Liquid

    Energy Technology Data Exchange (ETDEWEB)

    Welch, David A.; Woehl, Taylor J.; Park, Chiwoo; Faller, Roland; Evans, James E.; Browning, Nigel D.

    2016-01-20

    Optimization of colloidal nanoparticle synthesis techniques requires an understanding of underlying particle growth mechanisms. Non-classical growth mechanisms are particularly important as they affect nanoparticle size and shape distributions which in turn influence functional properties. For example, preferential attachment of nanoparticles is known to lead to the formation of mesocrystals, although the formation mechanism is currently not well understood. Here we employ in situ liquid cell scanning transmission electron microscopy (STEM) and steered molecular dynamics (SMD) simulations to demonstrate that the experimentally observed preference for end-to-end attachment of silver nanorods is a result of weaker solvation forces occurring at rod ends. SMD reveals that when the side of a nanorod approaches another rod, perturbation in the surface bound water at the nanorod surface creates significant energy barriers to attachment. Additionally, rod morphology (i.e. facet shape) effects can explain the majority of the side attachment effects that are observed experimentally.

  2. Antibody affinity maturation

    DEFF Research Database (Denmark)

    Skjødt, Mette Louise

    linker for yeast surface display of scFv and scFab fragments, we compared a series of different Gly-Ser-based linkers in display and antigen binding proficiency. We show that these formats of the model antibody can accommodate linkers of different lengths and that introduction of alanine or glutamate......-2. Based on the presented data we suggest that affinity maturation of the model antibody proceeds through multiple incremental steps of subtle improvements. We moreover conclude that the best affinity improved candidates are likely to be obtained through optimization of both the antigen...... fragments by in vivo homologous recombination large combinatorial antibody libraries can easily be generated. We have optimized ordered assembly of three CDR fragments into a gapped vector and observed increased transformation efficiency in a yeast strain carrying a deletion of the SGS1 helicase...

  3. 30 CFR 77.1436 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 77.1436 Section 77.1436... Hoisting Wire Ropes § 77.1436 Drum end attachment. (a) For drum end attachment, wire rope shall be attached... anchor bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist...

  4. Give Them Roots, Then Let Them Fly: Understanding Attachment Therapy.

    Science.gov (United States)

    McKelvey, Carole A., Ed.

    This book describes attachment theory, presents the attachment therapy program in place at the Evergreen Attachment Center at Evergreen, Colorado, and examines the implications of attachment therapy. The chapters are: (1) "An Overview" (Carole A. McKelvey, John Alston); (2) "Attachment Theory and Assessment" (Michael Orlans, Terry Levy); (3)…

  5. Antithyroglobulin Antibodies and Antimicrosomal Antibodies in Various Thyroid Diseases

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Gwon Jun; Hong, Key Sak; Choi, Kang Won; Lee, Kyu; Koh, Chang Soon; Lee, Mun Ho; Park, Sung Hoe; Chi, Je Geun; Lee, Sang Kook [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1979-03-15

    The authors investigated the incidence of antithyroglobulin antibodies and antibodies and antimicrosomal antibodies measured by tanned red cell hemagglutination method in subjects suffering from various thyroid disorders. 1) In 15 normal patients, neither suffering from any thyroid diseases nor from any other autoimmune disorders, the antithyroglobulin antibodies were all negative, but the antimicrosomal antibody was positive only in one patient (6.7%). 2) The antithyroglobulin antibodies were positive in 31.5% (34 patients) of 108 patients with various thyroid diseases, and the antimicrosomal antibodies were positive in 37.0% (40 patients). 3) of the 25 patients with Graves' diseases, 7 patients (28.0%) showed positive for the antithyroglobulin antibodies, and 9 (36.0%) for the antimicrosomal antibodies. There was no definite differences in clinical and thyroid functions between the groups with positive and negative results. 4) Both antibodies were positive in 16 (88.9%) and 17 (94.4%) patients respectively among 18 patients with Hashimoto's thyroiditis, all of them were diagnosed histologically. 5) Three out of 33 patients with thyroid adenoma showed positive antibodies, and 3 of 16 patients with thyroid carcinoma revealed positive antibodies. 6) TRCH antibodies demonstrated negative results in 2 patients with subacute thyroiditis, but positive in one patient with idiopathic primary myxedema. 7) The number of patients with high titers(>l:802) was 16 for antithyroglobulin antibody, and 62.5% (10 patients) of which was Hashimoto's thyroiditis. Thirteen (65.0) of 20 patients with high titers (>l:802) for antimicrosomal antibody was Hashimoto's thyroiditis. TRCH test is a simple, sensitive method, and has high reliability and reproducibility. The incidences and titers of antithyroglobulin antibody and antimicrosomal antibody are especially high in Hashimoto's thyroiditis.

  6. Targeting Antibodies to Carbon Nanotube Field Effect Transistors by Pyrene Hydrazide Modification of Heavy Chain Carbohydrates

    Directory of Open Access Journals (Sweden)

    Steingrimur Stefansson

    2012-01-01

    Full Text Available Many carbon nanotube field-effect transistor (CNT-FET studies have used immobilized antibodies as the ligand binding moiety. However, antibodies are not optimal for CNT-FET detection due to their large size and charge. Their size can prevent ligands from reaching within the Debye length of the CNTs and a layer of charged antibodies on the circuits can drown out any ligand signal. In an attempt to minimize the antibody footprint on CNT-FETs, we examined whether pyrene hydrazide modification of antibody carbohydrates could reduce the concentration required to functionalize CNT circuits. The carbohydrates are almost exclusively on the antibody Fc region and this site-specific modification could mediate uniform antibody orientation on the CNTs. We compared the hydrazide modification of anti-E. coli O157:H7 polyclonal antibodies to pyrenebutanoic acid succinimidyl ester-coated CNTs and carbodiimide-mediated antibody CNT attachment. Our results show that the pyrene hydrazide modification was superior to those methods with respect to bacteria detection and less than 1 nM labeled antibody was required to functionalize the circuits.

  7. Clinical evaluation of mandibular implant overdentures via Locator implant attachment and Locator bar attachment

    Science.gov (United States)

    Seo, Yong-Ho; Bae, Eun-Bin; Kim, Jung-Woo; Lee, So-Hyoun; Jeong, Chang-Mo; Jeon, Young-Chan

    2016-01-01

    PURPOSE The aim of this study was to evaluate the clinical findings and patient satisfaction on implant overdenture designed with Locator implant attachment or Locator bar attachment in mandibular edentulous patients. MATERIALS AND METHODS Implant survival rate, marginal bone loss, probing depth, peri-implant inflammation, bleeding, plaque, calculus, complications, and satisfaction were evaluated on sixteen patients who were treated with mandibular overdenture and have used it for at least 1 year (Locator implant attachment: n=8, Locator bar attachment: n=8). RESULTS Marginal bone loss, probing depth, plaque index of the Locator bar attachment group were significantly lower than the Locator implant attachment group (P.05). The replacement of the attachment components was the most common complication in both groups. Although there was no correlation between marginal bone loss and plaque index, a significant correlation was found between marginal bone loss and probing depth. CONCLUSION The Locator bar attachment group indicates lesser marginal bone loss and need for maintenance, as compared with the Locator implant attachment group. This may be due to the splinting effect among implants rather than the types of Locator attachment. PMID:27555901

  8. Cell-Free Synthesis Meets Antibody Production: A Review

    Directory of Open Access Journals (Sweden)

    Marlitt Stech

    2015-01-01

    Full Text Available Engineered antibodies are key players in therapy, diagnostics and research. In addition to full size immunoglobulin gamma (IgG molecules, smaller formats of recombinant antibodies, such as single-chain variable fragments (scFv and antigen binding fragments (Fab, have emerged as promising alternatives since they possess different advantageous properties. Cell-based production technologies of antibodies and antibody fragments are well-established, allowing researchers to design and manufacture highly specific molecular recognition tools. However, as these technologies are accompanied by the drawbacks of being rather time-consuming and cost-intensive, efficient and powerful cell-free protein synthesis systems have been developed over the last decade as alternatives. So far, prokaryotic cell-free systems have been the focus of interest. Recently, eukaryotic in vitro translation systems have enriched the antibody production pipeline, as these systems are able to mimic the natural pathway of antibody synthesis in eukaryotic cells. This review aims to overview and summarize the advances made in the production of antibodies and antibody fragments in cell-free systems.

  9. Dissecting antibodies with regards to linear and conformational epitopes.

    Science.gov (United States)

    Forsström, Björn; Axnäs, Barbara Bisławska; Rockberg, Johan; Danielsson, Hanna; Bohlin, Anna; Uhlen, Mathias

    2015-01-01

    An important issue for the performance and specificity of an antibody is the nature of the binding to its protein target, including if the recognition involves linear or conformational epitopes. Here, we dissect polyclonal sera by creating epitope-specific antibody fractions using a combination of epitope mapping and an affinity capture approach involving both synthesized peptides and recombinant protein fragments. This allowed us to study the relative amounts of antibodies to linear and conformational epitopes in the polyclonal sera as well as the ability of each antibody-fraction to detect its target protein in Western blot assays. The majority of the analyzed polyclonal sera were found to have most of the target-specific antibodies directed towards linear epitopes and these were in many cases giving Western blot bands of correct molecular weight. In contrast, many of the antibodies towards conformational epitopes did not bind their target proteins in the Western blot assays. The results from this work have given us insights regarding the nature of the antibody response generated by immunization with recombinant protein fragments and has demonstrated the advantage of using antibodies recognizing linear epitopes for immunoassay involving wholly or partially denatured protein targets. PMID:25816293

  10. Dissecting antibodies with regards to linear and conformational epitopes.

    Directory of Open Access Journals (Sweden)

    Björn Forsström

    Full Text Available An important issue for the performance and specificity of an antibody is the nature of the binding to its protein target, including if the recognition involves linear or conformational epitopes. Here, we dissect polyclonal sera by creating epitope-specific antibody fractions using a combination of epitope mapping and an affinity capture approach involving both synthesized peptides and recombinant protein fragments. This allowed us to study the relative amounts of antibodies to linear and conformational epitopes in the polyclonal sera as well as the ability of each antibody-fraction to detect its target protein in Western blot assays. The majority of the analyzed polyclonal sera were found to have most of the target-specific antibodies directed towards linear epitopes and these were in many cases giving Western blot bands of correct molecular weight. In contrast, many of the antibodies towards conformational epitopes did not bind their target proteins in the Western blot assays. The results from this work have given us insights regarding the nature of the antibody response generated by immunization with recombinant protein fragments and has demonstrated the advantage of using antibodies recognizing linear epitopes for immunoassay involving wholly or partially denatured protein targets.

  11. Cryogenic devices attached to electron accelerators

    International Nuclear Information System (INIS)

    The cryoeenic equipement attached to electron accelerators used at the CEN.G for fundamental research on point defects in solids is presented and some of their essential technical characteristics are briefly described

  12. Attachment and the Roots of Competence.

    Science.gov (United States)

    Sroufe, L. Alan

    1981-01-01

    Describes research with 12- to 18-month-old infants (N=108) determining whether the quality of an infant's attachment to his/her primary caregiver could predict the nature of his/her emerging personality. (CS)

  13. Are anxiously attached women better mindreaders?

    Science.gov (United States)

    Hünefeldt, Thomas; Laghi, Fiorenzo; Ortu, Francesca

    2013-08-01

    This research was aimed at providing first evidence concerning the relationship between adults' self-reported attachment style and their performance on a standard 'theory of mind' task. Based on adult attachment theory, we hypothesized that the two dimensions of self-reported adult attachment, anxiety and avoidance, are differently related to 'theory of mind,' and that this relationship is moderated by variables concerning the 'theory of mind' stimuli. The 'Experiences in Close Relationships' questionnaire and the 'Reading the Mind in the Eyes' test were administered to 132 young women. In line with our expectations, women's attachment-related anxiety was associated with better mind reading concerning stimuli that were emotionally neutral or difficult to recognize.

  14. Development of Anti-Isoproturon Polyclonal Antibody

    Institute of Scientific and Technical Information of China (English)

    LI Fang-shi; SUN Feng; LIU Xian-jin; CUI Heng-hua

    2007-01-01

    A competitive enzyme-linked immunosorbent assay (ELISA) suitable for the determination of the urea herbicide isoproturon,3-(4-isopropylphenyl)-1,1-dimethylurea, in food and environmental samples was developed. Two haptens named 1-(3-carboxypropyl)-3-(4-isopropylphenyl)-1-methylurca (hapten 4C) and 1-(5-carboxypentyl)-3-(4-isopropylphenyl)-1-methylurea (hapten 6C) were synthesized. The haptens were coupled to bovine serum albumin (BSA) and ovalbumin(OVA), respectively, using the N-hydroxysuccinimide reaction. The hapten 6C-BSA conjugate was used as the immunogen,with which a high-titer anti-isoproturon polyclonal antibody (pAb) was successfully obtained by immunization of New Zealand white rabbits. The hapten 4C-OVA conjugate was used as coating antigen and a method of the indirect competitive ELISA for isoproturon was established. The haptens were confirmed with TLC, IR, and 1H NMR. The conjugation molar ratios of hapten 4C to OVA and hapten 6C to BSA were 36:1 and 46:1, respectively, as calculated by a UV spectrophotometry.The highest titer of the anti-isoproturon sera determined by a non-competitive indirect ELISA procedure was 1.6×105. The optimal concentrations of the coating antigen and the dilution of the anti-isoproturon sera used in the ELISA were 0.1 mg L-1 and 1.0 × 105, respectively. The concentration of isoproturon that inhibits 50% of antibody-antigen binding (IC50) was 0.07 mg mL-1.The cross-reactivities of six urea herbicides including chlorbromuron, fluometuron, monolinuron were lower than 0.1%. Isoproturon is a small molecule without immune activity and active functional group for attaching to carrier protein. To produce an antibody against isoproturon with high titer and high specificity is the most important step in the development of an immunochemical method for the determination of isoproturon in food and environmental samples. The two haptens synthesized in this study have carboxyl groups and accommodate different lengths of spacer arms, and

  15. Attachment of Gold Nanoparticles to Carbon Nanotubes

    Institute of Scientific and Technical Information of China (English)

    Xi Cheng MA; Ning LUN; Shu Lin WEN

    2005-01-01

    Carbon nanotubes were initially chemically modified with an H2SO4-HNO3 treatment,and subsequently activated with Pd-Sn catalytic nuclei via a one-step activation approach. These activated nanotubes were used as precursors for obtaining gold nanoparticles-attached nanotubes via simple electroless plating. This approach provides an efficient method for attachment of metal nanostructures to carbon nanotubes. Such novel hybrid nanostructures are attractive for many applications.

  16. God as an Attachment Figure : A Case Study of the God Attachment Language and God Concepts of Anxiously Attached Christian Youths in South Africa

    NARCIS (Netherlands)

    Counted, Victor

    2016-01-01

    This study examines the role of the Christian God as an attachment figure, using the attachment language criteria of a strong and enduring affectionate bond. Respondents were 15 anxiously attached Christian youths, purposefully selected for in-depth interviews to explore their God attachment languag

  17. Structural basis for Marburg virus neutralization by a cross-reactive human antibody

    OpenAIRE

    Hashiguchi, Takao; Fusco, Marnie L.; Bornholdt, Zachary A.; Lee, Jeffrey E.; Flyak, Andrew I.; Matsuoka, Rei; Kohda, Daisuke; Yanagi, Yusuke; Hammel, Michal; Crowe, James E.; Saphire, Erica Ollmann

    2015-01-01

    The filoviruses, including Marburg and Ebola, express a single glycoprotein on their surface, termed GP, which is responsible for attachment and entry of target cells. Filovirus GPs differ by up to 70% in protein sequence, and no antibodies are yet described that cross-react among them. Here, we present the 3.6 Å crystal structure of Marburg virus GP in complex with a cross-reactive antibody from a human survivor, and a lower resolution structure of the antibody bound to Ebola virus GP. The a...

  18. Attachment of Adolescents to Parents: Turkey Profile

    Directory of Open Access Journals (Sweden)

    Turkan Dogan

    2016-12-01

    Full Text Available The present study aims to determine the attachment of adolescents to their parents according to geographical regions in Turkey and gender. The research group consisted of 6061 adolescents. With an age average of 15.53 years. The Inventory of Attachment to Parents and Friends- Brief Form (EABE was used as data acquisition tool. The results of the study indicated significant difference between the scores of students regarding the inventory of attachment to parents according to regions. Evaluating the findings regarding attachment to father and mother together, the findings were similar, and the attachment levels of adolescents in Middle Anatolia, Eastern Anatolia and Black Sea Region were found to be higher than the ones in other regions. This result may be related with socioeconomic, geographical and cultural structures of the regions. Examining the finding according to gender variable, the scores of male students are significantly lower than the scores of female students. As a result according to the data gained from a wide sample group; the main factors for the attachment of adolescents to their parents in Turkey are the geographical regions in Turkey and the gender. [Psikiyatride Guncel Yaklasimlar - Current Approaches in Psychiatry 2016; 8(4.000: 406-419

  19. Removable partial overdentures with mechanical (precision) attachments.

    Science.gov (United States)

    Mensor, M C

    1990-10-01

    Mechanical attachments for overdentures have been available in various forms for over a century. The explosive interest in osseointegration and the effort on the part of the profession to avoid the complete denture as a treatment modality has stirred the interest in positive retentive elements for overdentures represented by the mechanical stud and bar attachments. The cited references provide a resource as a trouble-free guide in the selection and use of the various stud and bar attachment systems. The clinical examples show a pattern of application not generally discussed by the manufacturers, illustrating the simplicity of use with the options for all attachments including magnets. The discussion on magnets comes from 9 years of clinical experience. Rare earth magnets provide excellent adjunct retention, and their assembly follows the same protocol and complexity as stud attachment systems. All magnets, at the present state of the art, have a corrosion potential with the exception of the Laser Sealed Units (Golden Dental, Golden, CO). Finally, the mechanics of the attachment overdenture serves as an excellent training field for the osseointegrated prosthesis, be it the classic Brånemark (Nobelpharma USA, Chicago, IL) restorative or the implant overdenture concept. PMID:2227040

  20. Attachment Theory and the Social Work Curriculum

    Directory of Open Access Journals (Sweden)

    Timothy Page

    2007-05-01

    Full Text Available Attachment theory, as developed by Bowlby and Ainsworth, represented a major departure from the current theories of human development of the time, particularly in its rejection of the major tenets of psychoanalytic theory and its integration of core ideas from evolution theory and cybernetics (Ainsworth & Bowlby, 1991. Attachment theory posits that a foundational human instinct, the desire to achieve safety and protection through proximity to a protective figure, is responsible for the formation of a special class of life-long affectional bonds, referred to as “attachments.” Emotional security is derived to a great extent, according to the theory, from experience with caregivers who are consistently responsive to the developing infant’s expression of attachment behavior toward them. Forty years of empirical research has shown that attachment is a universal characteristic that predicts children’s development of cognitive and social competence, emotional regulation, and positive self-image (Weinfield, Sroufe, Egeland, & Carlson, 1999. Social work educators are currently challenged to better integrate the findings of attachment research into their curricula to reflect more the current state of developmental science.

  1. Developing recombinant antibodies for biomarker detection

    Energy Technology Data Exchange (ETDEWEB)

    Baird, Cheryl L.; Fischer, Christopher J.; Pefaur, Noah B.; Miller, Keith D.; Kagen, Jacob; Srivastava, Sudhir; Rodland, Karin D.

    2010-10-01

    Monoclonal antibodies (mAbs) have an essential role in biomarker validation and diagnostic assays. A barrier to pursuing these applications is the reliance on immunization and hybridomas to produce mAbs, which is time-consuming and may not yield the desired mAb. We recommend a process flow for affinity reagent production that utilizes combinatorial protein display systems (eg, yeast surface display or phage display) rather than hybridomas. These systems link a selectable phenotype-binding conferred by an antibody fragment-with a means for recovering the encoding gene. Recombinant libraries obtained from immunizations can produce high-affinity antibodies (<10 nM) more quickly than other methods. Non-immune libraries provide an alternate route when immunizations are not possible, or when suitable mAbs are not recovered from an immune library. Directed molecular evolution (DME) is an integral part of optimizing mAbs obtained from combinatorial protein display, but can also be used on hybridoma-derived mAbs. Variants can easily be obtained and screened to increase the affinity of the parent mAb (affinity maturation). We discuss examples where DME has been used to tailor affinity reagents to specific applications. Combinatorial protein display also provides an accessible method for identifying antibody pairs, which are necessary for sandwich-type diagnostic assays.

  2. Neutralizing antibodies in hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    Mirjam B Zeisel; Samira Fafi-Kremer; Isabel Fofana; Heidi Barth; Fran(c)oise Stoll-Keller; Michel Doffo(e)l; Thomas F Baumert

    2007-01-01

    Hepatitis C virus (HCV) is a major cause of hepatitis world-wide. The majority of infected individuals develop chronic hepatitis which can then progress to liver cirrhosis and hepatocellular carcinoma. Spontaneous viral clearance occurs in about 20%-30% of acutely infected individuals and results in resolution of infection without sequaelae. Both viral and host factors appear to play an important role for resolution of acute infection. A large body of evidence suggests that a strong, multispecific and long-lasting cellular immune response appears to be important for control of viral infection in acute hepatitis C. Due too the lack of convenient neutralization assays,the impact of neutralizing responses for control of viral infection had been less defined. In recent years, the development of robust tissue culture model systems for HCV entry and infection has finally allowed study of antibody-mediated neutralization and to gain further insights into viral targets of host neutralizing responses.In addition, detailed analysis of antibody-mediated neutralization in individual patients as well as cohorts with well defined viral isolates has enabled the study of neutralizing responses in the course of HCV infection and characterization of the impact of neutralizing antibodies for control of viral infection. This review will summarize recent progress in the understanding of the molecular mechanisms of antibody-mediated neutralization and its impact for HCV pathogenesis.(C) 2007 The WJG Press. All rights reserved.

  3. Monoclonal antibodies in myeloma

    DEFF Research Database (Denmark)

    Sondergeld, P.; van de Donk, N. W. C. J.; Richardson, P. G.;

    2015-01-01

    The development of monoclonal antibodies (mAbs) for the treatment of disease goes back to the vision of Paul Ehrlich in the late 19th century; however, the first successful treatment with a mAb was not until 1982, in a lymphoma patient. In multiple myeloma, mAbs are a very recent and exciting add...

  4. Prediction of Antibody Epitopes

    DEFF Research Database (Denmark)

    Nielsen, Morten; Marcatili, Paolo

    2015-01-01

    self-proteins. Given the sequence or the structure of a protein of interest, several methods exploit such features to predict the residues that are more likely to be recognized by an immunoglobulin.Here, we present two methods (BepiPred and DiscoTope) to predict linear and discontinuous antibody...

  5. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

    Directory of Open Access Journals (Sweden)

    Liliana R. Loureiro

    2015-08-01

    Full Text Available The carbohydrate antigens Tn and sialyl-Tn (STn are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment.

  6. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

    Science.gov (United States)

    Loureiro, Liliana R.; Carrascal, Mylène A.; Barbas, Ana; Ramalho, José S.; Novo, Carlos; Delannoy, Philippe; Videira, Paula A.

    2015-01-01

    The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment. PMID:26270678

  7. Structure, attachment properties, and ecological importance of the attachment system of English ivy (Hedera helix)

    OpenAIRE

    Melzer, Björn; Seidel, Robin; Steinbrecher, Tina; Speck, Thomas

    2011-01-01

    Root climbers such as English ivy (Hedera helix) rely on specialized adventitious roots for attachment, enabling the plants to climb on a wide range of natural and artificial substrates. Despite their importance for the climbing habit, the biomechanical properties of these specialized adventitious roots compared with standard roots and their performance in the attachment to different host species or inert substrates have not been studied. Here organs and tissues involved in the attachment are...

  8. Neurobiology of secure infant attachment and attachment despite adversity: a mouse model

    OpenAIRE

    Roth, T.L.; Raineki, C.; Salstein, L.; Perry, R; Wilson, T. A. Sullivan; Sloan, A.; Lalji, B.; Hammock, E.; Wilson, D. A.; Levitt, P; Okutani, F.; Kaba, H. (Harry); R.M. Sullivan

    2013-01-01

    Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltr...

  9. Lupus anticoagulants and antiphospholipid antibodies

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000547.htm Lupus anticoagulants and antiphospholipid antibodies To use the sharing features on this page, please enable JavaScript. Lupus anticoagulants are antibodies against substances in the lining ...

  10. Attachment, personality, and psychopathology among adult inpatients: self-reported romantic attachment style versus Adult Attachment Interview states of mind.

    Science.gov (United States)

    Riggs, Shelley A; Paulson, Adrienne; Tunnell, Ellen; Sahl, Gayla; Atkison, Heather; Ross, Colin A

    2007-01-01

    The present study examined self-reported romantic attachment style and Adult Attachment Interview (AAI) states of mind regarding early attachment relationships, personality dimensions, and psychopathology in a psychiatric sample of trauma survivors. Inpatients (N = 80) admitted to a hospital trauma treatment program were administered the Experiences in Close Relationships Scale, AAI, Millon Clinical Multiaxial Inventory-III, Dissociative Experiences Scale, and Dissociative Disorder Interview Schedule. Self-report and AAI attachment classifications were not related, and different results emerged for the two measures. Self-reported romantic attachment style was significantly associated with personality dimensions, with fearful adults showing the most maladaptive personality profiles. Findings suggested that self-report dimensions of self and other independently contribute to different forms of psychological dysfunction. AAI unresolved trauma was uniquely associated with dissociation and posttraumatic stress disorder, whereas unresolved trauma and unresolved loss jointly contributed to schizotypal and borderline personality disorder scores. The differences in findings between the two measures are discussed with a view toward the developmental and clinical implications. PMID:17241494

  11. Recombinant antibodies and tumor targeting

    OpenAIRE

    Sheikholvaezin, Ali

    2006-01-01

    Different antibody derived constructs are rapidly advancing as putative tools for treatment of malignant diseases. Antibody engineering has added significant new technologies to modify size, affinities, solubility, stability and biodistribution properties for immunoconjugates. In the present thesis, the aim was to increase our knowledge on how new recombinant antibodies could be tailored to optimize localization to experimental tumors in mice. One hybridoma, producing the monoclonal antibody ...

  12. A double antibody radioimmunoassay for mouse hemoglobins: use of polyethylene glycol in conjunction with the second antibody

    International Nuclear Information System (INIS)

    A double antibody radioimmunoassay (RIA) system is described for detection of small quantities of hemoglobins. Mouse (C57BL/6) hemoglobin and horse anti-mouse hemoglobin antiserum were used to develop the system. The first phase of the RIA, i.e., the initial reaction between the antigen and the antibody, was found to be complete within 24 h. The reaction proceeded better at 40C than at 250C. The second phase, i.e., separation of bound from unbound antigen, was achieved by precipitation with a second antibody (goat anti-horse IgG) and polyethlene glycol (PEG). A 50 g/l concentration of PEG was found to be best suited for the assay. Mixing of all the reagents together was found to decrease the binding as compared to the system in which second antibody and PEG were added after completion of the first phase. Maximum precipitation of the complex took place within 30 min after the addition of the second antibody and 1 h after the addition of 50 g/l PEG. The RIA system described here combines the conventional double antibody RiA with the PEG method. This method has decreased the amount of time necessary for precipitation from 24 h (or longer) to 1 h. Large molecular weight antigens could not be estimated in the conventional PEG method because of their insolubility in 200 g/l PEG utilized in the assay. The use of a low concentration of PEG along with the second antibody in the method described here allows the estimation of large molecular weight antigens. This double antibody-PEG method has a general applicability for small as well as large molecular weight antigens. (Auth.)

  13. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K.; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-07-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

  14. Inhibition of HIV Virus by Neutralizing Vhh Attached to Dual Functional Liposomes Encapsulating Dapivirine.

    Science.gov (United States)

    Wang, Scarlet Xiaoyan; Michiels, Johan; Ariën, Kevin K; New, Roger; Vanham, Guido; Roitt, Ivan

    2016-12-01

    Although highly active antiretroviral therapy (HAART) has greatly improved the life expectancy of HIV/AIDS patients, the treatment is not curative. It is a global challenge which fosters an urgent need to develop an effective drug or neutralizing antibody delivery approach for the prevention and treatment of this disease. Due to the low density of envelope spikes with restricted mobility present on the surface of HIV virus, which limit the antibody potency and allow virus mutation and escape from the immune system, it is important for a neutralizing antibody to form bivalent or multivalent bonds with the virus. Liposome constructs could fulfil this need due to the flexible mobility of the membrane with its attached antibodies and the capacity for drug encapsulation. In this study, we evaluated the neutralization activity of a range of liposome formulations in different sizes coated with anti-gp120 llama antibody fragments (Vhhs) conjugated via either non-covalent metal chelation or a covalent linkage. The non-covalent construct demonstrated identical binding affinity to HIV-1 envelope glycoprotein gp120 and neutralizing ability for HIV virus as free Vhh. Although covalently linked Vhh showed significant binding affinity to gp120, it unexpectedly had a lower neutralization potency. This may be due to the comparability in size of the viral and liposome particles restricting the number which can be bound to the liposome surface so involving only a fraction of the antibodies, whereas non-covalently attached antibodies dissociate from the surface after acting with gp120 and free the remainder to bind further viruses. Covalently conjugated Vhh might also trigger the cellular uptake of a liposome-virion complex. To explore the possible ability of the antibody-coated liposomes to have a further function, we encapsulated the hydrophobic antiviral drug dapivirine into both of the non-covalently and covalently conjugated liposome formulations, both of which revealed high

  15. Selection of Arginine-Rich Anti-Gold Antibodies Engineered for Plasmonic Colloid Self-Assembly

    CERN Document Server

    Jain, Purvi; Narayanan, S Shankara; Sharma, Jadab; Girard, Christian; Dujardin, Erik; Nizak, Clément

    2014-01-01

    Antibodies are affinity proteins with a wide spectrum of applications in analytical and therapeutic biology. Proteins showing specific recognition for a chosen molecular target can be isolated and their encoding sequence identified in vitro from a large and diverse library by phage display selection. In this work, we show that this standard biochemical technique rapidly yields a collection of antibody protein binders for an inorganic target of major technological importance: crystalline metallic gold surfaces. 21 distinct anti-gold antibody proteins emerged from a large random library of antibodies and were sequenced. The systematic statistical analysis of all the protein sequences reveals a strong occurrence of arginine in anti-gold antibodies, which corroborates recent molecular dynamics predictions on the crucial role of arginine in protein/gold interactions. Once tethered to small gold nanoparticles using histidine tag chemistry, the selected antibodies could drive the self-assembly of the colloids onto t...

  16. Antibody mimetics: promising complementary agents to animal-sourced antibodies.

    Science.gov (United States)

    Baloch, Abdul Rasheed; Baloch, Abdul Wahid; Sutton, Brian J; Zhang, Xiaoying

    2016-01-01

    Despite their wide use as therapeutic, diagnostic and detection agents, the limitations of polyclonal and monoclonal antibodies have inspired scientists to design the next generation biomedical agents, so-called antibody mimetics that offer many advantages over conventional antibodies. Antibody mimetics can be constructed by protein-directed evolution or fusion of complementarity-determining regions through intervening framework regions. Substantial progress in exploiting human, butterfly (Pieris brassicae) and bacterial systems to design and select mimetics using display technologies has been made in the past 10 years, and one of these mimetics [Kalbitor® (Dyax)] has made its way to market. Many challenges lie ahead to develop mimetics for various biomedical applications, especially those for which conventional antibodies are ineffective, and this review describes the current characteristics, construction and applications of antibody mimetics compared to animal-sourced antibodies. The possible limitations of mimetics and future perspectives are also discussed. PMID:25264572

  17. Parental incarceration, attachment and child psychopathology.

    Science.gov (United States)

    Murray, Joseph; Murray, Lynne

    2010-07-01

    Theory and evidence relating parental incarceration, attachment, and psychopathology are reviewed. Parental incarceration is a strong risk factor for long-lasting psychopathology, including antisocial and internalizing outcomes. Parental incarceration might threaten children's attachment security because of parent-child separation, confusing communication about parental absence, restricted contact with incarcerated parents, and unstable caregiving arrangements. Parental incarceration can also cause economic strain, reduced supervision, stigma, home and school moves, and other negative life events for children. Thus, there are multiple possible mechanisms whereby parental incarceration might increase risk for child psychopathology. Maternal incarceration tends to cause more disruption for children than paternal incarceration and may lead to greater risk for insecure attachment and psychopathology. Children's prior attachment relations and other life experiences are likely to be of great importance for understanding children's reactions to parental incarceration. Several hypotheses are presented about how prior insecure attachment and social adversity might interact with parental incarceration and contribute to psychopathology. Carefully designed longitudinal studies, randomized controlled trials, and cross-national comparative research are required to test these hypotheses.

  18. Surface-attachment sequence in Vibrio Cholerae

    Science.gov (United States)

    Utada, Andrew; Gibiansky, Maxsim; Wong, Gerard

    2013-03-01

    Vibrio cholerae is a gram-negative bacterium that causes the human disease cholera. It is found natively in brackish costal waters in temperate climates, where it attaches to the surfaces of a variety of different aquatic life. V. cholerae has a single polar flagellum making it highly motile, as well as a number of different pili types, enabling it to attach to both biotic and abiotic surfaces. Using in-house built tracking software we track all surface-attaching bacteria from high-speed movies to examine the early-time attachment profile of v. cholerae onto a smooth glass surface. Similar to previous work, we observe right-handed circular swimming trajectories near surfaces; however, in addition we see a host of distinct motility mechanisms that enable rapid exploration of the surface before forming a more permanent attachment. Using isogenic mutants we show that the motility mechanisms observed are due to a complex combination of hydrodynamics and pili-surface interactions. Lauga, E., DiLuzio, W. R., Whitesides, G. M., Stone, H. A. Biophys. J. 90, 400 (2006).

  19. Discovery of functional monoclonal antibodies targeting G-protein-coupled receptors and ion channels.

    Science.gov (United States)

    Wilkinson, Trevor C I

    2016-06-15

    The development of recombinant antibody therapeutics is a significant area of growth in the pharmaceutical industry with almost 50 approved monoclonal antibodies on the market in the US and Europe. Despite this growth, however, certain classes of important molecular targets have remained intractable to therapeutic antibodies due to complexity of the target molecules. These complex target molecules include G-protein-coupled receptors and ion channels which represent a large potential target class for therapeutic intervention with monoclonal antibodies. Although these targets have typically been addressed by small molecule approaches, the exquisite specificity of antibodies provides a significant opportunity to provide selective modulation of these target proteins. Given this opportunity, substantial effort has been applied to address the technical challenges of targeting these complex membrane proteins with monoclonal antibodies. In this review recent progress made in the strategies for discovery of functional monoclonal antibodies for these challenging membrane protein targets is addressed. PMID:27284048

  20. Parent Attachment, Childrearing Behavior, and Child Attachment: Mediated Effects Predicting Preschoolers' Externalizing Behavior

    Science.gov (United States)

    Roskam, Isabelle; Meunier, Jean-Christophe; Stievenart, Marie

    2011-01-01

    Attachment theory provides an interesting background for thinking about externalizing behavior (EB) in early childhood and for understanding how parenting influences the child's outcomes. The study examined how attachment and parenting could be combined to explain preschoolers' EB. Data were collected from 117 preschoolers aged from 4 to 6…

  1. Measuring Lifestyle and Attachment: An Empirical Investigation Linking Individual Psychology and Attachment Theory

    Science.gov (United States)

    Peluso, Paul R.; Peluso, Jennifer P.; Buckner, Janine P.; Kern, Roy M.; Curlette, William

    2009-01-01

    P. R. Peluso, J. P. Peluso, J. F. White, and R. M. Kern (2004) reviewed the theoretical constructs underlying the similarities between lifestyle and attachment style. Specifically, they suggested that the individual psychology construct of lifestyle (or style of life) and attachment style should be empirically investigated. The present research…

  2. Maternal Attachment Representations, Maternal Sensitivity, and the Infant-Mother Attachment Relationship.

    Science.gov (United States)

    Pederson, David R.; Gleason, Karin E.; Moran, Greg; Bento, Sandi

    1998-01-01

    Examined the mediating role of maternal sensitivity for the association between maternal attachment representations and the quality of infant-mother attachment. Found that autonomous mothers and mothers in secure relationships were more sensitive at home than nonautonomous mothers and mothers in nonsecure relationships, respectively. Infants in…

  3. A monoclonal antibody against leptin.

    Science.gov (United States)

    Mahmoudian, Jafar; Jeddi-Tehrani, Mahmood; Bayat, Ali Ahmad; Mahmoudi, Ahmad Reza; Vojgani, Yasaman; Tavangar, Banafsheh; Hadavi, Reza; Zarei, Saeed

    2012-10-01

    Leptin is an important protein that regulates energy storage and homeostasis in humans and animals. Leptin deficiency results in various abnormalities such as diabetes, obesity, and infertility. Producing a high affinity monoclonal antibody against human leptin provides an important tool to monitor and trace leptin function in different biological fluids. In this study, recombinant human leptin was conjugated to KLH and injected into mice. After immunization, mouse myeloma SP2/0 cells were fused with murine splenocytes followed by selection of antibody-producing hybridoma cells. After screening of different hybridoma colonies by ELISA, a high affinity antibody was selected and purified by affinity chromatography. The affinity constant of the antibody was measured by ELISA. Western blot, immunocytochemistry, and flow cytometry experiments were used to characterize the antibody. The anti-leptin antibody had a high affinity (around 1.13 × 10(-9) M) for its antigen. The saturation of the antibody with leptin (20 moles leptin per 1 mole antibody) in Western blot analysis proved that the antibody had specific binding to its antigen. Immunocytochemistry and flow cytometry on JEG-3 (human placental choriocarcinoma cell) cells revealed that the anti-leptin antibody recognized intracellular leptin. In conclusion, we report here the production and characterization of a murine anti-leptin antibody with high affinity for human leptin. PMID:23098305

  4. Attachment theory: a biological basis for psychotherapy?

    Science.gov (United States)

    Holmes, J

    1993-10-01

    John Bowlby bemoaned the separation between the biological and psychological approaches in psychiatry, and hoped that attachment theory, which brings together psychoanalysis and the science of ethology, would help bridge the rift between them. Recent findings in developmental psychology have delineated features of parent-infant interaction, especially responsiveness, attunement, and modulation of affect, which lead to either secure or insecure attachment. Similar principles can be applied to the relationship between psychotherapist and patient--the provision of a secure base, the emergence of a shared narrative ('autobiographical competence'), the processing of affect, coping with loss--these are common to most effective psychotherapies and provide the basis for a new interpersonal paradigm within psychotherapy. Attachment theory suggests they rest on a sound ethological and hence biological foundation.

  5. Engineering antibodies by yeast display.

    Science.gov (United States)

    Boder, Eric T; Raeeszadeh-Sarmazdeh, Maryam; Price, J Vincent

    2012-10-15

    Since its first application to antibody engineering 15 years ago, yeast display technology has been developed into a highly potent tool for both affinity maturing lead molecules and isolating novel antibodies and antibody-like species. Robust approaches to the creation of diversity, construction of yeast libraries, and library screening or selection have been elaborated, improving the quality of engineered molecules and certainty of success in an antibody engineering campaign and positioning yeast display as one of the premier antibody engineering technologies currently in use. Here, we summarize the history of antibody engineering by yeast surface display, approaches used in its application, and a number of examples highlighting the utility of this method for antibody engineering.

  6. Antiphospholipid Antibody and Antiphospholipid Syndrome

    Institute of Scientific and Technical Information of China (English)

    吴竞生

    2008-01-01

    @@ Antiphospholipid antibodies (APA) APA is a big category for all kinds of negative charge phospholipid or lecithin - a protein complex autoantibodies or the same antibody, through its recognition of antigen (target protein) different, and phospholipids or lecithin - protein complex combination of various rely on the interference Phospholipid clotting and anti-coagulation factor, and promote endothelial cells, platelets, complement activation and play a role. APA including lupus anticoagulant(LA) and anticardiolipin antibody (ACA), In addition, there are anti-β2 glycoprotein-I (β2-GPI) antibody, anti-prothrombin (a- PT) antibody, anti-lysophosphatidic acid antibody and anti-phosphatidylserine antibody, and so on. APA as the main target of phospholipid-binding protein, including β2-GPI, prothrombin, annexin, protein C (PC) and protein S (PS), plasminogen, and so on.

  7. Antibody dependent enhancement of frog virus 3 infection

    Directory of Open Access Journals (Sweden)

    Penny Emily

    2010-02-01

    Full Text Available Abstract Background Viruses included in the family Iridoviridae are large, icosahedral, dsDNA viruses that are subdivided into 5 genera. Frog virus 3 (FV3 is the type species of the genus Ranavirus and the best studied iridovirus at the molecular level. Typically, antibodies directed against a virus act to neutralize the virus and limit infection. Antibody dependent enhancement occurs when viral antibodies enhance infectivity of the virus rather than neutralize it. Results Here we show that anti-FV3 serum present at the time of FV3 infection enhances infectivity of the virus in two non-immune teleost cell lines. We found that antibody dependent enhancement of FV3 was dependent on the Fc portion of anti-FV3 antibodies but not related to complement. Furthermore, the presence of anti-FV3 serum during an FV3 infection in a non-immune mammalian cell line resulted in neutralization of the virus. Our results suggest that a cell surface receptor specific to teleost cell lines is responsible for the enhancement. Conclusions This report represents the first evidence of antibody dependent enhancement in iridoviruses. The data suggests that anti-FV3 serum can either neutralize or enhance viral infection and that enhancement is related to a novel antibody dependent enhancement pathway found in teleosts that is Fc dependent.

  8. Pathogenic and Epiphenomenal Anti-DNA Antibodies in SLE

    Directory of Open Access Journals (Sweden)

    Mirjana Pavlovic

    2010-01-01

    Full Text Available The discoveries of natural and the development of manufactured highly efficient catalytic antibodies (abzymes opens the door to many practical applications. One of the most fascinating is the use of such antibodies in human therapy and prevention (vaccination, of cancer, AIDS, autoimmune diseases. A special entity of naturally occurring DNA hydrolytic anti-DNA antibodies is emerging within past decades linked to autoimmune and lymphoproliferative disorders, such as systemic lupus erythematosus (SLE, multiple sclerosis (MS, Sjogren Syndrome (SS, B - Chronic lymphocytic leucosis (B-CLL, and Multiple Myeloma (MM. The origin of the antibodies is unknown. The underlying mechanisms of these activities are suggested to be penetration into the living cells and translocation in the nucleus, with recognition of the specific binding sites at particular (ss or ds DNA. There are controversies in the literature whether hydrolysis is a sequence-specific event. The interplay between anti-DNA antibodies and DNA is not yet elucidated. This molecular “twist” also suggests that anti-DNA antibodies with DNA hydrolytic capacity could be the organism's immune response to a microbial attack, with microbial DNA, or specific genes within microbial DNA sequence, as a target for neutralization. The catalytic antibody-based approach can become a key tool in selective chemotherapeutic strategies.

  9. Family systems theory, attachment theory, and culture.

    Science.gov (United States)

    Rothbaum, Fred; Rosen, Karen; Ujiie, Tatsuo; Uchida, Nobuko

    2002-01-01

    Family systems theory and attachment theory have important similarities and complementarities. Here we consider two areas in which the theories converge: (a) in family system theorists' description of an overly close, or "enmeshed," mother-child dyad, which attachment theorists conceptualize as the interaction of children's ambivalent attachment and mothers' preoccupied attachment; (b) in family system theorists' description of the "pursuer-distance cycle" of marital conflict, which attachment theorists conceptualize as the interaction of preoccupied and dismissive partners. We briefly review family systems theory evidence, and more extensively review attachment theory evidence, pertaining to these points of convergence. We also review cross-cultural research, which leads us to conclude that the dynamics described in both theories reflect, in part, Western ways of thinking and Western patterns of relatedness. Evidence from Japan suggests that extremely close ties between mother and child are perceived as adaptive, and are more common, and that children experience less adverse effects from such relationships than do children in the West. Moreover, in Japan there is less emphasis on the importance of the exclusive spousal relationship, and less need for the mother and father to find time alone to rekindle romantic, intimate feelings and to resolve conflicts by openly communicating their differences. Thus, the "maladaptive" pattern frequently cited by Western theorists of an extremely close mother-child relationship, an unromantic, conflictual marriage characterized by little verbal communication and a peripheral, distant father, may function very differently in other cultures. While we believe that both theories will be greatly enriched by their integration, we caution against the application of either theory outside the cultures in which they were developed.

  10. Human Monoclonal Antibodies Targeting Glypican-2 in Neuroblastoma | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    Researchers at the National Cancer Institute’s Laboratory of Molecular Biology (NCI LMB) have developed and isolated several single domain monoclonal human antibodies against GPC2. NCI seeks parties interested in licensing or co-developing GPC2 antibodies and/or conjugates.

  11. Effect of attachment strategies on bipartite networks

    DEFF Research Database (Denmark)

    Ganguly, N.; Saha, S.; Maiti, A.;

    2013-01-01

    rate. Here, we focus on the case where one of the partitions can be assumed to be fixed while the other partition grows in time as observed in the codon-gene or alphabet-word network. We show that subtle changes in growth dynamics, particularly in the attachment kernel, can lead to drastic changes...... of the emergent topological properties. We present a detail analysis of various growth strategies, including sequential and parallel addition of nodes, as well as with and without replacement attachment kernels. Analytical results have been compared with stochastic simulations as well as with real systems showing...

  12. Assortativity in generalized preferential attachment models

    CERN Document Server

    Krot, Alexander

    2016-01-01

    In this paper, we analyze assortativity of preferential attachment models. We deal with a wide class of preferential attachment models (PA-class). It was previously shown that the degree distribution in all models of the PA-class follows a power law. Also, the global and the average local clustering coefficients were analyzed. We expand these results by analyzing the assortativity property of the PA-class of models. Namely, we analyze the behavior of $d_{nn}(d)$ which is the average degree of a neighbor of a vertex of degree $d$.

  13. Development of indirect competitive fluorescence immunoassay for 2,2′,4,4′-tetrabromodiphenyl ether using DNA/dye conjugate as antibody multiple labels

    Institute of Scientific and Technical Information of China (English)

    Zi-Yan Fan; Young Soo Keum; Qing-Xiao Li; Weilin L. Shelver; Liang-Hong Guo

    2012-01-01

    An indirect competitive fluorescence immunoassay using a DNA/dye conjugate as antibody multiple labels was developed on 96-well plates for the identification and quantification of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) in aqueous samples.A hapten,2,4,2′-tribromodiphenyl ether-4′-aldehyde,was synthesized,and was conjugated to bovine serum albumin to form a coating antigen,Specific recognition of the antigen by anti-PBDE antiserum was confirmed by a surface plasmon resonance measurement.In the immunoassay,the coating antigen was adsorbed on a 96-well plate first,and a sample,antiserum and biotinylated goat anti-rabbit secondary antibody were then added and reacted sequentially.A biotinylated,double-stranded DNA with 219 base pairs was attached to the secondary antibody by using streptavidin as a molecular bridge.In situ multiple labeling of the antibody was accomplished after addition of a DNA-binding fluorescent dye,SYBR Green I.The working range of the immunoassay for the BDE-47 standard was 3.1-390 μg/L,with an IC50 value of 15.6 μg/L.The calculated LOD of the immunoassay is 0.73 μg/L.The immunoassay demonstrated relatively high selectivity for BDE-47,showing very low cross-reactivity (< 3%) with BDE-15,BDE-153 and BDE-209.With a spiked river water sample containing 50 μg/L BDE-47,quantification by the immunoassay was 41.9 μg/L,which compared well with the standard GC-ECD method (45.7 μg/L).The developed immunoassay provides a rapid screening tool for polybrominated diphenyl ethers in environmental samples.

  14. 30 CFR 57.19026 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 57.19026 Section 57.19026... Wire Ropes § 57.19026 Drum end attachment. (a) For drum end attachment, wire rope shall be attached— (1... bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist drum....

  15. 30 CFR 56.19026 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 56.19026 Section 56.19026... Ropes § 56.19026 Drum end attachment. (a) For drum end attachment, wire rope shall be attached— (1... bolts, clamps, or wedges, provided that the attachment is a design feature of the hoist drum....

  16. 30 CFR 75.1436 - Drum end attachment.

    Science.gov (United States)

    2010-07-01

    ... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Drum end attachment. 75.1436 Section 75.1436... attachment. (a) For drum end attachment, wire rope shall be attached— (1) Securely by clips after making one... that the attachment is a design feature of the hoist drum. Design feature means either the...

  17. Attachment and the Processing of Social Information in Adolescence

    Science.gov (United States)

    Dykas, Matthew J.; Cassidy, Jude

    2007-01-01

    A key proposition of attachment theory is that experience-based cognitive representations of attachment, often referred to as internal working models of attachment, influence the manner in which individuals process attachment-relevant social information (Bowlby, 1969/1982, 1973, 1980; Bretherton & Munholland, 1999; Main, Kaplan, & Cassidy, 1985).…

  18. Neuroglian-positive plasmatocytes of Manduca sexta and the initiation of hemocyte attachment to foreign surfaces.

    Science.gov (United States)

    Nardi, James B; Pilas, Barbara; Bee, Charles Mark; Zhuang, Shufei; Garsha, Karl; Kanost, Michael R

    2006-01-01

    Observations of hemocyte aggregation on abiotic surfaces suggested that certain plasmatocytes from larvae of Manduca sexta act as foci for hemocyte aggregation. To establish how these particular plasmatocytes form initial attachments to foreign surfaces, they were cultured separately from other selected populations of hemocytes. While all circulating plasmatocytes immunolabel with anti-beta-integrin monoclonal antibody (MAb), only these larger plasmatocytes immunolabel with a MAb to the adhesion protein neuroglian. Neuroglian-negative plasmatocytes and granular cells that have been magnetically segregated from the majority of granular cells adhere to each other but fail to adhere to foreign substrata; by contrast, neuroglian-positive plasmatocytes that segregate with most granular cells adhere firmly to a substratum. Hemocytes form stable aggregates around the large, neuroglian-positive plasmatocytes. However, if neuroglian-positive plasmatocytes are separated from most granular cells, attachment of these plasmatocytes to foreign surfaces is suppressed. PMID:16171863

  19. A comparison of a solid phase IRC assay and the PSIFT for detection of antibodies to platelets.

    Science.gov (United States)

    Häcker-Shahin, B; Giannitsis, D J

    1992-01-01

    A rapid solid phase indicator red cells assay (IRCA) for detection of platelet antibodies was developed and its sensitivity compared with PSIFT. Platelets were attached to the surface of polystyrene microtitre plate wells by means of a sodium carbonate buffer and centrifugation. Uncovered areas were blocked by a gelatin blocking buffer. After serum incubation bound platelet-specific antibodies were made visible by anti-IgG-coated indicator red cells and a brief centrifugation. A positive result, meaning the presence of an anti-platelet antibody was indicated by red cell adherence over the reaction surface. In the absence of serum antibodies to platelets the indicator red cells formed a pellet. The IRCA showed a high sensitivity; the anti-platelet antibody Thrombocyte was detectable until a dilution of 1:1,600 whereas the same antibody in the PSIFT could only be detected until a dilution of 1:400.

  20. Mouse Monoclonal Antibodies for Liver Cancer Research | NCI Technology Transfer Center | TTC

    Science.gov (United States)

    The National Cancer Institute Laboratory of Molecular Biology seeks parties for collaborative research to co-develop and commercialize antibody drug/toxin conjugates as liver cancer therapy and diagnostics.

  1. A mouse monoclonal antibody against Alexa Fluor 647.

    Science.gov (United States)

    Wuethrich, Irene; Guillen, Eduardo; Ploegh, Hidde L

    2014-04-01

    Fluorophores are essential tools in molecular and cell biology. However, their application is mostly confined to the singular exploitation of their fluorescent properties. To enhance the versatility and expand the use of the fluorophore Alexa Fluor 647 (AF647), we generated a mouse monoclonal antibody against it. We demonstrate its use of AF647 for immunoblot, immunoprecipitation, and cytofluorimetry.

  2. A role for anti-HSP60 antibodies in arthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing; Bennike, Tue; Christiansen, Gunna;

    2013-01-01

    As a result of the high sequence similarity between HSP60 proteins, found in both prokaryotic and eukaryotic cells, it has been suggested, but never concluded, that anti-HSP60 antibodies could be of importance in the pathology of arthritis diseases explained by a concept named molecular mimicry...

  3. Characterization of Binding Epitopes of CA125 Monoclonal Antibodies

    DEFF Research Database (Denmark)

    Marcos-Silva, Lara; Narimatsu, Yoshiki; Halim, Adnan;

    2014-01-01

    The most used cancer serum biomarker is the CA125 immunoassay for ovarian cancer that detects the mucin glycoprotein MUC16. Several monoclonal antibodies (mAbs) including OC125 and M11 are used in CA125 assays. However, despite considerable efforts, our knowledge of the molecular characteristics ...

  4. Development of Lathe Attachment for a CNC Machine

    Science.gov (United States)

    Roy, V.; Kumar, S.

    2013-04-01

    A lathe attachment has been developed for an existing CNC machine (installed with rapid prototyping attachment) using conceptual design. The CNC machine operates on mechatronic controls and a computer interface called CAMSOFT, and is used as a CNC Lathe after installing the respective attachment to it. The conceptual design phase, starts from an idea and different components of the lathe are designed as attachment using CAD modelling and is followed by fabrication phase. The lathe attachment is successfully developed and is installed to the CNC machine. The working of the CNC Lathe attachment is checked by making some machining operation like turning and thread cutting. The machining operations are successfully done. The CNC machine becomes multifunctional with the presently developed lathe attachment and the existing RP (rapid prototyping) attachment, and can be used accordingly by installing the respective attachment to it. The CNC machine is useful for carrying research work in both the fields, when installed with the appropriate attachment.

  5. Active screen plasma nitriding enhances cell attachment to polymer surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Kaklamani, Georgia, E-mail: g.kaklamani@bham.ac.uk [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom); Bowen, James; Mehrban, Nazia [University of Birmingham, College of Engineering and Physical Sciences, School of Chemical Engineering, Edgbaston, Birmingham B15 2TT (United Kingdom); Dong, Hanshan [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom); Grover, Liam M. [University of Birmingham, College of Engineering and Physical Sciences, School of Chemical Engineering, Edgbaston, Birmingham B15 2TT (United Kingdom); Stamboulis, Artemis [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2013-05-15

    Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N{sub 2}/H{sub 2} ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast-coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of C-N, C=N, and C≡N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media.

  6. Low energy electron attachment to cyanamide (NH2CN)

    International Nuclear Information System (INIS)

    Cyanamide (NH2CN) is a molecule relevant for interstellar chemistry and the chemical evolution of life. In the present investigation, dissociative electron attachment to NH2CN has been studied in a crossed electron–molecular beams experiment in the electron energy range from about 0 eV to 14 eV. The following anionic species were detected: NHCN−, NCN−, CN−, NH2−, NH−, and CH2−. The anion formation proceeds within two broad electron energy regions, one between about 0.5 and 4.5 eV and a second between 4.5 and 12 eV. A discussion of possible reaction channels for all measured negative ions is provided. The experimental results are compared with calculations of the thermochemical thresholds of the anions observed. For the dehydrogenated parent anion, we explain the deviation between the experimental appearance energy of the anion with the calculated corresponding reaction threshold by electron attachment to the isomeric form of NH2CN—carbodiimide

  7. Electron attachment to antipyretics: Possible implications of their metabolic pathways

    Science.gov (United States)

    Pshenichnyuk, Stanislav A.; Modelli, Alberto

    2012-06-01

    The empty-level structures and formation of negative ion states via resonance attachment of low-energy (0-15 eV) electrons into vacant molecular orbitals in a series of non-steroidal anti-inflammatory drugs (NSAIDs), namely aspirin, paracetamol, phenacetin, and ibuprofen, were investigated in vacuo by electron transmission and dissociative electron attachment (DEA) spectroscopies, with the aim to model the behavior of these antipyretic agents under reductive conditions in vivo. The experimental findings are interpreted with the support of density functional theory calculations. The negative and neutral fragments formed by DEA in the gas phase display similarities with the main metabolites of these commonly used NSAIDs generated in vivo by the action of cytochrome P450 enzymes, as well as with several known active agents. It is concluded that xenobiotic molecules which possess pronounced electron-accepting properties could in principle follow metabolic pathways which parallel the gas-phase dissociative decay channels observed in the DEA spectra at incident electron energies below 1 eV. Unwanted side effects as, e.g., hepatoxicity or carcinogenicity produced by the NSAIDs under study in human organism are discussed within the "free radical model" framework, reported earlier to describe the toxic action of the well-known model toxicant carbon tetrachloride.

  8. Involvement of a vitronectin-like protein in attachment of Agrobacterium tumefaciens to carrot suspension culture cells.

    OpenAIRE

    Wagner, V T; Matthysse, A G

    1992-01-01

    Infections of dicotyledonous plants by Agrobacterium tumefaciens result in the formation of crown gall tumors. Attachment of the bacteria to plant host cells is required for tumor formation. Human vitronectin and antivitronectin antibodies both inhibited the binding of A. tumefaciens to carrot cells. Wild-type bacteria are able to bind radioactive vitronectin; nonattaching mutants showed a reduction in the ability to bind vitronectin. The binding of biotype 1 A. tumefaciens to carrot cells or...

  9. Childhood Abuse and Attachment Styles of Adolescents

    Science.gov (United States)

    Karakus, Ozlem

    2012-01-01

    Introduction: The fact that emotional and social experiences in early childhood period within the family influence the experiences in adolescence and adulthood (communication skills, interpersonal relations) is not a new case. Therefore, the aim of this study is to examine the relationship between childhood abuse and attachment styles. Method: The…

  10. Should Charity Donations Have Strings Attached?

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The commonly held belief among most people is that acts of charity are carried out with no thought of getting something in return, or of attaching conditions to those who receive donations. It’s perhaps for this rea- son that events surrounding the Henan Charity Federation’s recent decision to add an agenda to students’ financial aid caused such a public outcry.

  11. Hidden Regulators in Attachment, Separation, and Loss.

    Science.gov (United States)

    Hofer, Myron A.

    1994-01-01

    This essay discusses the similarities between animal behavior and human attachment behavior demonstrated by infants and their mothers. The provision of warmth, the tactile and olfactory stimulation of the mother's physical interactions, and the oral sensory and absorptive consequences of nursing are found to provide specific and independent…

  12. Ammonium and attachment of Rhodopirellula baltica.

    Science.gov (United States)

    Frank, Carsten S; Langhammer, Philipp; Fuchs, Bernhard Maximilian; Harder, Jens

    2011-05-01

    A dimorphic life cycle has been described for the planctomycete Rhodopirellula baltica SH1(T), with juvenile motile, free-swimming cells and adult sessile, attached-living cells. However, attachment as a response to environmental factors was not investigated. We studied the response of R. baltica to nitrogen limitation. In batch cultures, ammonium limitation coincided with a dominance of free-swimming cells and a low number of aggregates. Flow cytometry revealed a quantitative shift with increasing ammonium availability, from single cells towards attached cells in large aggregates. During growth of R. baltica on glucose and ammonium in chemostats, an ammonium addition caused a macroscopic change of the growth behaviour, from homogeneous growth in the liquid phase to a biofilm on the borosilicate glass wall of the chemostat vessel. Thus, an ammonium limitation-a carbon to nitrogen supply ratio of 30:1-sustained free-living growth without aggregate formation. A sudden increase in ammonium supply induced sessile growth of R. baltica. These observations reveal a response of Rhodopirellula baltica cells to ammonium: they abandon the free-swimming life, attach to particles and form biofilms. PMID:21340506

  13. No Strings Attached: Open Source Solutions

    Science.gov (United States)

    Fredricks, Kathy

    2009-01-01

    Imagine downloading a new software application and not having to worry about licensing, finding dollars in the budget, or incurring additional maintenance costs. Imagine finding a Web design tool in the public domain--free for use. Imagine major universities that provide online courses with no strings attached. Imagine online textbooks without a…

  14. Maternal anxiety, maternal sensitivity, and attachment

    NARCIS (Netherlands)

    Stevenson-Hinde, J.; Chicot, R.; Schouldice, A.; Hinde, C.A.

    2013-01-01

    Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety levels

  15. Maternal anxiety, maternal sensitivity, and attachment

    NARCIS (Netherlands)

    Stevenson-Hinde, Joan; Chicot, Rebecca; Shouldice, Anne; Hinde, Camilla A.

    2016-01-01

    Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety leve

  16. Bowlby's attachment theory: implications for health visiting.

    Science.gov (United States)

    Partis, M

    2000-10-01

    This article reviews the current state of research in attachment theory. It also examines the relations between attachment, child care and development, and the significance of attachment to adult functioning and well-being. It seems likely that humans need close emotional relationships or bonds with others. This need applies particularly to infants, who look to parents or other care givers for love and security. The best-known psychological explanation of this need is attachment theory, which has been influential in increasing our understanding of the early mother-infant relationship, and in the formulation of guidelines for child care (Melhuish, 1998). Good-quality parental care may be difficult to define, and questions remain regarding the nature of child care and the consequences that it can have for later development. This article concludes with a discussion of the possible implications for health-visitor intervention within families, which are intended to improve the quality of the relationship between parents or care givers and the infant.

  17. Attachment Styles, Abuse Experiences and Depression

    Science.gov (United States)

    Gunduz, Bulent; Capri, Burhan; Akbay, Sinem Evin; Tunc, Aygul

    2013-01-01

    This study aims to examine the relationship between abuse experiences, depression and attachment styles. The data for this study was collected from 251 students (123 females and 128 males) who attend Mersin University. As a part of the data collection, students completed the Experiences in Affiliation Inventory, Childhood Trauma Scale and Brief…

  18. Infant attachment, adult attachment, and maternal sensitivity: revisiting the intergenerational transmission gap.

    Science.gov (United States)

    Behrens, Kazuko Y; Haltigan, John D; Bahm, Naomi I Gribneau

    2016-08-01

    This study investigated the intergenerational transmission of attachment, utilizing the Adult Attachment Interview (AAI), the Strange Situation Procedure (SSP), and the Maternal Behavioral Q-Set (MBQS). We revisited fundamental questions in attachment theory and research by examining: (1) the level of intergenerational agreement between maternal attachment representations and infant attachment security, and (2) whether maternal sensitivity serves as an intergenerational mediator between adult and infant attachment security. Significant categorical matches between the AAI and the SSP as well as mean differences for MBQS scores between adult attachment secure-insecure groups were found. Consistent with earlier intergenerational research, maternal sensitivity only partially mediated the AAI-SSP link, indicating the transmission gap remains. Consistent with recent mediation studies, using more contemporary analytical techniques, it was confirmed that maternal sensitivity did mediate the direct pathway between AAI security and SSP security. Thus, the transmission gap appears somewhat different depending on the statistical method used to measure mediation. Post hoc analyses considered mothers' childhood experiences of separation/divorce and this helped make sense of intergenerational mismatches.

  19. Comparative validity of the Adult Attachment Interview and the Adult Attachment Projective.

    Science.gov (United States)

    Jones-Mason, Karen; Allen, I Elaine; Hamilton, Steve; Weiss, Sandra J

    2015-01-01

    The Adult Attachment Interview (AAI) and the Adult Attachment Projective (AAP) purport to measure the same attachment classifications. The aims of this study were to determine the concurrent validity of the AAI and AAP, and to compare their ability to predict indicators of risk associated with socioeconomic status (SES), depression, and 5-HTTLPR genotype. Results indicated no agreement between AAI and AAP attachment classifications in a sample of late adolescents. As predicted, individuals classified as "unresolved" with regard to loss or trauma were significantly more likely to be of lower SES, have higher levels of depression, and have the 5-HTTLPR "ss" genotype than individuals with secure, preoccupied, or dismissing attachments. These associations, however, were only significant when attachment was classified with the AAI. Results suggest that the AAI and AAP measure different facets of attachment as a result of their unique methodologies and coding criteria. Further research is needed to support their comparability before investigators can assume that the AAP is a valid substitute for the AAI. PMID:26362584

  20. Infant attachment, adult attachment, and maternal sensitivity: revisiting the intergenerational transmission gap.

    Science.gov (United States)

    Behrens, Kazuko Y; Haltigan, John D; Bahm, Naomi I Gribneau

    2016-08-01

    This study investigated the intergenerational transmission of attachment, utilizing the Adult Attachment Interview (AAI), the Strange Situation Procedure (SSP), and the Maternal Behavioral Q-Set (MBQS). We revisited fundamental questions in attachment theory and research by examining: (1) the level of intergenerational agreement between maternal attachment representations and infant attachment security, and (2) whether maternal sensitivity serves as an intergenerational mediator between adult and infant attachment security. Significant categorical matches between the AAI and the SSP as well as mean differences for MBQS scores between adult attachment secure-insecure groups were found. Consistent with earlier intergenerational research, maternal sensitivity only partially mediated the AAI-SSP link, indicating the transmission gap remains. Consistent with recent mediation studies, using more contemporary analytical techniques, it was confirmed that maternal sensitivity did mediate the direct pathway between AAI security and SSP security. Thus, the transmission gap appears somewhat different depending on the statistical method used to measure mediation. Post hoc analyses considered mothers' childhood experiences of separation/divorce and this helped make sense of intergenerational mismatches. PMID:27056466

  1. Sexuality examined through the lens of attachment theory: attachment, caregiving, and sexual satisfaction.

    Science.gov (United States)

    Péloquin, Katherine; Brassard, Audrey; Lafontaine, Marie-France; Shaver, Phillip R

    2014-01-01

    Attachment researchers have proposed that the attachment, caregiving, and sexual behavioral systems are interrelated in adult love relationships (Mikulincer & Shaver, 2007 ). This study examined whether aspects of partners' caregiving (proximity, sensitivity, control, compulsive caregiving) mediated the association between their attachment insecurities (anxiety and avoidance) and each other's sexual satisfaction in two samples of committed couples (Study 1: 126 cohabiting or married couples from the general community; Study 2: 55 clinically distressed couples). Partners completed the Experiences in Close Relationships measure (Brennan, Clark, & Shaver, 1998 ), the Caregiving Questionnaire (Kunce & Shaver, 1994 ), and the Global Measure of Sexual Satisfaction (Lawrance & Byers, 1998 ). Path analyses based on the actor-partner interdependence model (APIM) revealed that caregiving proximity mediated the association between low attachment avoidance and partners' sexual satisfaction in distressed and nondistressed couples. Sensitivity mediated this association in nondistressed couples only. Control mediated the association between men's insecurities (attachment-related avoidance and anxiety) and their partners' low sexual satisfaction in nondistressed couples. Attachment anxiety predicted compulsive caregiving, but this caregiving dimension was not a significant mediator. These results are discussed in light of attachment theory and their implications for treating distressed couples.

  2. Attachment issues: kinetochore transformations and spindle checkpoint silencing.

    Science.gov (United States)

    Etemad, Banafsheh; Kops, Geert J P L

    2016-04-01

    Cell division culminates in the segregation of duplicated chromosomes in opposite directions prior to cellular fission. This process is guarded by the spindle assembly checkpoint (SAC), which prevents the anaphase of cell division until stable connections between spindle microtubules and the kinetochores of all chromosomes are established. The anaphase inhibitor is generated at unattached kinetochores and inhibitor production is prevented when microtubules are captured. Understanding the molecular changes in the kinetochore that are evoked by microtubule attachments is crucial for understanding the mechanisms of SAC signaling and silencing. Here, we highlight the most recent findings on these events, pinpoint some remaining mysteries, and argue for incorporating holistic views of kinetochore dynamics in order to understand SAC silencing. PMID:26947988

  3. THERMOPHILE ENDOSPORES HAVE RESPONSIVE EXOSPORIUM FOR ATTACHMENT

    Energy Technology Data Exchange (ETDEWEB)

    PANESSA-WARREN,B.; TORTORA,G.T.; WARREN,J.; SABATINI,R.

    1999-08-01

    Recently studies examining the colonization of Clostridial pathogens on agar and human tissue culture cells, demonstrated that (C. sporogenes ATCC 3584, C. difficile ATCC 43594 [patient isolate], C. difficile ATCC 9689 [non-clinical], C. clostridioforme [patient isolate]) bacterial spores (endospores) of the genus Clostridia have an outer membrane that becomes responsive at activation and exhibits extensions of the exosporial membrane that facilitate and maintain spore attachment to a nutritive substrate during germination and initial outgrowth of the newly developed bacterial cell. Therefore this attachment phenomenon plays an important role in insuring bacterial colonization of a surface and the initial stages of the infective process. To see if other non-clinical members of this genus also have this ability to attach to a substrate or food-source during spore germination, and how this attachment process in environmental thermophiles compares to the clinical paradigm (in relation to time sequence, exosporial membrane structure, type of attachment structures, composition of the membrane etc...), sediment samples were collected in sterile transport containers at 4 geothermal sites at Yellowstone National Park in Wyoming. Because spore forming bacteria will produce spores when conditions are unfavorable for growth, the samples were sealed and stored at 4 C. After 8 months the samples were screened for the presence of spores by light microscope examination using malachite green/safranin, and traditional endospores were identified in significant quantities from the Terrace Spring site (a 46 C lake with bacterial mats and a rapidly moving run-off channel leading to a traditional hot spring). The highest spore population was found in the top sediment and benthic water of the run-off channel, pH 8.1.

  4. The antibody Hijikata Tatsumi

    Directory of Open Access Journals (Sweden)

    Éden Peretta

    2012-11-01

    Full Text Available Considered one of the most influential modern dance representatives in Japan, Tatsumi Hijikata’s work was a milestone in the Japanese post-war experimental artistic scene. Heretic son of his time, he staged a fertile mix of artistic and cultural influences, overlapping subversive elements of European arts and philosophy with radical references from pre-modern Japanese culture. In this way he built the foundations of its unstable antibody, its political-artistic project of dissolution of a organism, both physical and social.

  5. Electron attachment rate constant measurement by photoemission electron attachment ion mobility spectrometry (PE-EA-IMS)

    Science.gov (United States)

    Su, Desheng; Niu, Wenqi; Liu, Sheng; Shen, Chengyin; Huang, Chaoqun; Wang, Hongmei; Jiang, Haihe; Chu, Yannan

    2012-12-01

    Photoemission electron attachment ion mobility spectrometry (PE-EA-IMS), with a source of photoelectrons induced by vacuum ultraviolet radiation on a metal surface, has been developed to study electron attachment reaction at atmospheric pressure using nitrogen as the buffer gas. Based on the negative ion mobility spectra, the rate constants for electron attachment to tetrachloromethane and chloroform were measured at ambient temperature as a function of the average electron energy in the range from 0.29 to 0.96 eV. The experimental results are in good agreement with the data reported in the literature.

  6. The Effect of Birth Order on Attachment Style According to Attachment Theory

    OpenAIRE

    BAYRAKTAR, Seda; YAHŞİ, Gülşah

    2016-01-01

    Attachment is a vital neurobiopsychological phenomenon known to be dependent on the early relationship between baby and the caregiver. It mostly develops in the first year and out of repeated patterns of the primary attachment relationship. Birth order is defined as a person's rank by age among his or her siblings. Birth order is often believed to have a profound and lasting effect on psychological development. Also it has been thought that birth order has an impact on the attachment.  In thi...

  7. Dissociative Electron Attachment to Hydrocarbons. A Laboratory Study

    Science.gov (United States)

    Szymanska, E.; Mason, N. J.

    2011-05-01

    Laboratory studies of PAHs continue to be essential if we are to interpret the wealth and variety of processes contributing to star formation. In the realm of gas-phase kinetics reactions involving negative ions are being studied to help modellers understand the role of these species in interstellar chemistry. Observations have shown that PAHs molecules are abundant and ubiquitous in the interstellar medium of galaxies, play an important role in its physical and chemical characteristics and form a key link between small hydrocarbon species and large carbonaceous grains. There is therefore considerable interest in the mechanisms by which these molecules and their anions may form. One method is electron induced chemistry within the icy mantles on the surface of dust grains. In particular it has been recently shown that functional group dependence exists in electron attachment processes giving rise to site selective fragmentation of molecules at the C-H, O-H and N-H bonds at energies well beyond the threshold for the breaking of any of these bonds allowing novel forms of chemistry that have little or no activation barriers, such as are necessary in the ISM. In this poster we present the results of recent studies on dissociative electron attachment (DEA) to PAHs using an improved version of a Velocity Map Imaging (VMI) spectrometer comprised of a magnetically collimated and low energy pulsed electron gun, a Faraday cup, an effusive molecular beam, a pulsed field ion extraction, a time of flight analyzer and a two-dimensional position sensitive detector consisting of microchannel plate and a phosphor screen. The VMI spectrometer measures the kinetic energy and angular distribution of the fragment anions produced in the dissociative electron attachment process. Kinetic energy measurements provide information on the internal energies of the fragment anions and determine the dissociation limits of the parent negative ion resonant states responsible for the dissociative

  8. Attachment: A Study of a Child's Attachment to the Teacher as an Outgrowth of Her/His Attachment to the Mother.

    Science.gov (United States)

    Houston, Ann Jespersen

    This paper reviews the literature on attachment, presents a study of child-teacher attachment, and discusses child-teacher attachment as a secondary relationship influenced by the prototype bonding between mother and child. The literature review traces the development of psychoanalytic thought regarding the mother-child relationship and examines…

  9. DETECTION OF THE BOVINE VIRAL DIARRHEA ANTIBODIES

    Directory of Open Access Journals (Sweden)

    I. V. Goraichuk

    2013-06-01

    Full Text Available Bovine viral diarrhea is a widespread infection of cattle that has a wide range of clinical symptoms in domestic and wild ruminants. It is a major problem in cattle and causes significant economic losses in the cattle industry. The virus infects bovines of all ages and causes both immunosuppression and reproductive, respiratory and digestive disorders. Persistently infected cattle are the main factor in transmission of the disease between and among herds. Comparative results of antibodies presence received by two methods of enzymoimmunoassay and virus neutralization test are given in the paper. During the work, 1010 samples of blood serum of cattle from three farms in the Kharkiv region were selected and analyzed. Bovine viral diarrhea virus concerning antibodies were found by enzymoimmunoassay in 704 samples (69.7% using commercial kit and in 690 samples (68.3% using in house method. After results clarification by virus neutralization test, bovine viral diarrhea antibodies were found in 712 samples (70.5%. Immunoenzyme analysis is recommended for mass screening of cattle for viral diarrhea occurrence. The results confirm that the sensitivity immunoenzyme analysis satisfies the requirements of the diagnostic methods. Using the neutralization reaction of viruses as the «gold standard» of serological methods, it is appropriate to clarify the results of immunoenzyme analysis. Since the results contain a signi ficant number of false positive results, it is necessary to carry out comprehensive studies using both serological and molecular genetics methods.

  10. VIRAL ANTIBODIES IN PRESCHOOL CHILDREN

    Directory of Open Access Journals (Sweden)

    S. Saidi

    1974-08-01

    Full Text Available One hundred sera from children 1 - 6 years of age, representative of a large serum collection, were tested for the prevalence of antibodies against different viruses. Hemagglutination-inhibition (HI antibodies were found in 68% for measles; 61 % for rubella; 75'% for influenza A2/Hong Kong/68, 16% for influenza B/Md./59, 0% for group A arboviruses, 10% for group B arboviruses, 3% for phlebotomus fever group and 4% for Congo-Crimean hemorrhagic fever (C-CHF group of arboviruses Poliomyelitis-neutralizing antibodies for type 1, 2 and 3 were 90%; 85% and 84%~ respectively. Antibody to EH virus was detected in 84% of the sera by immuno-fluorescence. None of the sera were positive for hepatitis-B antigen or antibody by immuno-precipitation test. The prevalence of some viral antibodies found in this survey are compared with results obtained from surveys in other parts of the country.

  11. An Insertion Mutation That Distorts Antibody Binding Site Architecture Enhances Function of a Human Antibody

    Energy Technology Data Exchange (ETDEWEB)

    Krause, Jens C.; Ekiert, Damian C.; Tumpey, Terrence M.; Smith, Patricia B.; Wilson, Ian A.; Crowe, Jr., James E. (Vanderbilt); (Scripps); (CDC)

    2011-09-02

    The structural and functional significance of somatic insertions and deletions in antibody chains is unclear. Here, we demonstrate that a naturally occurring three-amino-acid insertion within the influenza virus-specific human monoclonal antibody 2D1 heavy-chain variable region reconfigures the antibody-combining site and contributes to its high potency against the 1918 and 2009 pandemic H1N1 influenza viruses. The insertion arose through a series of events, including a somatic point mutation in a predicted hot-spot motif, introduction of a new hot-spot motif, a molecular duplication due to polymerase slippage, a deletion due to misalignment, and additional somatic point mutations. Atomic resolution structures of the wild-type antibody and a variant in which the insertion was removed revealed that the three-amino-acid insertion near the base of heavy-chain complementarity-determining region (CDR) H2 resulted in a bulge in that loop. This enlarged CDR H2 loop impinges on adjacent regions, causing distortion of the CDR H1 architecture and its displacement away from the antigen-combining site. Removal of the insertion restores the canonical structure of CDR H1 and CDR H2, but binding, neutralization activity, and in vivo activity were reduced markedly because of steric conflict of CDR H1 with the hemagglutinin antigen.

  12. Dissociative electron attachments to ethanol and acetaldehyde: A combined experimental and simulation study

    Science.gov (United States)

    Wang, Xu-Dong; Xuan, Chuan-Jin; Feng, Wen-Ling; Tian, Shan Xi

    2015-02-01

    Dissociation dynamics of the temporary negative ions of ethanol and acetaldehyde formed by the low-energy electron attachments is investigated by using the anion velocity map imaging technique and ab initio molecular dynamics simulations. The momentum images of the dominant fragments O-/OH- and CH3- are recorded, indicating the low kinetic energies of O-/OH- for ethanol while the low and high kinetic energy distributions of O- ions for acetaldehyde. The CH3- image for acetaldehyde also shows the low kinetic energy. With help of the dynamics simulations, the fragmentation processes are qualitatively clarified. A new cascade dissociation pathway to produce the slow O- ion via the dehydrogenated intermediate, CH3CHO- (acetaldehyde anion), is proposed for the dissociative electron attachment to ethanol. After the electron attachment to acetaldehyde molecule, the slow CH3- is produced quickly in the two-body dissociation with the internal energy redistributions in different aspects before bond cleavages.

  13. Metrics for antibody therapeutics development

    OpenAIRE

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approv...

  14. Empowered Antibody Therapies - IBC conference.

    Science.gov (United States)

    Herold, Jens

    2010-10-01

    The Empowered Antibody Therapies conference, held in Burlingame, CA, USA, included topics covering new therapeutic developments in the field of multispecific antibodies. This conference report highlights selected presentations on DVD-Igs from Abbott Laboratories, ImmTACs from Immunocore, 'Dock-and-Lock' technology from Immunomedics, the bispecific BiTE antibody blinatumomab from Micromet, and Triomabs from TRION Pharma and Fresenius Biotech. PMID:20878591

  15. Monoclonal antibodies for treating cancer

    International Nuclear Information System (INIS)

    The purpose of this study is to assess the current status of in-vivo use of monoclonal antibodies for treating cancer. Publications appearing between 1980 and 1988 were identified by computer searches using MEDLINE and CANCERLIT, by reviewing the table of contents of recently published journals, and by searching bibliographies of identified books and articles. More than 700 articles, including peer-reviewed articles and book chapters, were identified and selected for analysis. The literature was reviewed and 235 articles were selected as relevant and representative of the current issues and future applications for in-vivo monoclonal antibodies for cancer therapy and of the toxicity and efficacy which has been associated with clinical trials. Approaches include using antibody alone (interacting with complement or effector cells or binding directly with certain cell receptors) and immunoconjugates (antibody coupled to radioisotopes, drugs, toxins, or other biologicals). Most experience has been with murine antibodies. Trials of antibody alone and radiolabeled antibodies have confirmed the feasibility of this approach and the in-vivo trafficking of antibodies to tumor cells. However, tumor cell heterogeneity, lack of cytotoxicity, and the development of human antimouse antibodies have limited clinical efficacy. Although the immunoconjugates are very promising, heterogeneity and the antimouse immune response have hampered this approach as has the additional challenge of chemically or genetically coupling antibody to cytotoxic agents. As a therapeutic modality, monoclonal antibodies are still promising but their general use will be delayed for several years. New approaches using human antibodies and reducing the human antiglobulin response should facilitate treatment. 235 references

  16. Amended Final Report - Antibodies to Radionuclides. Engineering by Surface Display for Immunosensors

    Energy Technology Data Exchange (ETDEWEB)

    Blake, Diane A. [Tulane Univ., New Orleans, LA (United States)

    2013-06-14

    The relatively new techniques of antibody display, which permit molecular engineering of antibody structure and function, have the potential to revolutionize the way scientists generate binding proteins for specific applications. However, the skills required to efficiently use antibody display techniques have proven difficult for other laboratories to acquire without hands-on training and exchange of laboratory personnel. This research project is designed bring important expertise in antibody display to the State of Louisiana while pursuing a project with direct relevance to the DOE’s EM program.

  17. Antineutrophil cytoplasmic antibodies

    Directory of Open Access Journals (Sweden)

    G.D. Sebastiani

    2011-06-01

    Full Text Available Antineutrophil cytoplasmic antibodies (ANCA are predominantly IgG autoantibodies directed against constituents of primary granules of neutrophils and monocytes’ lysosomes. Although several antigenic targets have been identified, those ANCA directed to proteinase 3 or myeloperoxidase are clinically relevant, whereas the importance of other ANCA remains unknown. Both are strongly associated with small vessel vasculitides, the ANCA-associated vasculitides, which include Wegener’s granulomatosis, microscopic polyangiitis, and Churg-Strauss syndrome, and the localised forms of these diseases (eg, pauci-immune necrotising and crescentic glomerulonephritis. ANCA is a useful serological test to assist in diagnosis of small-vessel vasculitides. 85-95% of patients with Wegener’s granulomatosis, microscopic polyangiitis, and pauci-immune necrotising and crescentic glomerulonephritis have serum ANCA. ANCA directed to either proteinase 3 or myeloperoxidase are clinically relevant, yet the relevance of other ANCA remains unknown. Besides their diagnostic potential, ANCA might be valuable in disease monitoring. In addition, data seem to confirm the long-disputed pathogenic role of these antibodies. There is increasing evidence that myeloperoxidase- ANCA are directly involved in the pathogenesis of necrotizing vasculitis. This is less clear for proteinase 3-ANCA, markers for Wegener’s granulomatosis. With respect to proteinase 3-ANCA, complementary proteinase 3, a peptide translated from the antisense DNA strand of proteinase 3 and homologous to several microbial peptides, may be involved in induction of proteinase 3-antineutrophil cytoplasmic autoantibodies.

  18. Investigation of antigen-antibody interactions of sulfonamides with a monoclonal antibody in a fluorescence polarization immunoassay using 3D-QSAR models

    Science.gov (United States)

    A three-dimensional quantitative structure-activity relationship (3D-QSAR) model of sulfonamide analogs binding a monoclonal antibody (MAbSMR) produced against sulfamerazine was carried out by Distance Comparison (DISCOtech), comparative molecular field analysis (CoMFA), and comparative molecular si...

  19. A polar ring endows improved specificity to an antibody fragment.

    Science.gov (United States)

    Schaefer, Zachary P; Bailey, Lucas J; Kossiakoff, Anthony A

    2016-07-01

    Engineering monovalent Fab fragments into bivalent formats like IgGs or F(ab')2 can lead to aggregation presumably because of nonspecific off-target interactions that induce aggregation. In an effort to further understand the molecular determinants of nonspecific interactions for engineered antibodies and natively folded proteins in general, we focused on a synthetic Fab with low nanomolar affinity to histone chaperone Anti-silencing factor 1 (Asf1) that demonstrates off-target binding through low solubility (∼5 mg/mL) in the multivalent F(ab') 2 state. Here, we generated phage display-based shotgun scanning libraries to introduce aspartate as a negative design element into the antibody paratope. The antibody-combining site was amenable to aspartate substitution at numerous positions within the antigen binding loops and one variant, Tyr(L93) Asp/His(L94) Asp/Thr(H100b) Asp, possessed high solubility (>100 mg/ml). Furthermore, the mutations decreased nonspecific interactions measured by column interaction chromatography and ELISA in the multivalent antibody format while maintaining high affinity to the antigen. Structural determination of the antibody-antigen complex revealed that the aspartate-permissive residues formed a polar ring around the structural and functional paratope, recapitulating the canonical feature of naturally occurring protein-protein interactions. This observation may inform future strategies for the design and engineering of molecular recognition. PMID:27334407

  20. Role of a bacillus Calmette-Guérin fibronectin attachment protein in BCG-induced antitumor activity.

    Science.gov (United States)

    Zhao, W; Schorey, J S; Bong-Mastek, M; Ritchey, J; Brown, E J; Ratliff, T L

    2000-04-01

    Intravesical Mycobacterium bovis bacillus Calmette-Gu*erin (BCG) is the treatment of choice for superficial bladder cancer. Previous studies showed that attachment of BCG to fibronectin within the bladder was necessary for mediation of the antitumor response. Further studies identified a bacterial receptor, fibronectin attachment protein (FAP), as an important mediator of BCG attachment to fibronectin. In vitro studies showed that a stable BCG/fibronectin interaction was dependent on FAP binding to fibronectin; however, no role for FAP in the attachment of BCG in vivo has been characterized. We now report the cloning of the M. bovis BCG FAP (FAP-B) and demonstrate an important role for FAP in the in vivo attachment of BCG to the bladder wall and in the induction of BCG-mediated antitumor activity. The predicted amino acid sequence for FAP-B shows 61% and 71% homology, respectively, with Mycobacterium avium FAP (FAP-A) and Mycobacterium leprae FAP (FAP-L). Rabbit polyclonal antibodies against Mycobacterium vaccae FAP (FAP-V) reacted with all 3 recombinant FAP proteins on Western blots. Functional studies show FAP-B to bind fibronectin via the highly conserved attachment regions previously identified for FAP-A and FAP-L and also to competitively inhibit attachment of BCG to matrix fibronectin. In vivo studies show FAP to be a necessary protein for the stable attachment of BCG to the bladder wall. Moreover, stable binding of BCG via FAP was shown to be necessary for the expression of BCG-induced antitumor activity. Our results demonstrate a biological role for FAP in the mediation of BCG-induced antitumor activity.

  1. Porcine dentin sialoprotein glycosylation and glycosaminoglycan attachments

    Directory of Open Access Journals (Sweden)

    Yamakoshi Fumiko

    2011-02-01

    Full Text Available Abstract Background Dentin sialophosphoprotein (Dspp is a multidomain, secreted protein that is critical for the formation of tooth dentin. Mutations in DSPP cause inherited dentin defects categorized as dentin dysplasia type II and dentinogenesis imperfecta type II and type III. Dentin sialoprotein (Dsp, the N-terminal domain of dentin sialophosphoprotein (Dspp, is a highly glycosylated proteoglycan, but little is known about the number, character, and attachment sites of its carbohydrate moieties. Results To identify its carbohydrate attachment sites we isolated Dsp from developing porcine molars and digested it with endoproteinase Glu-C or pronase, fractionated the digestion products, identified fractions containing glycosylated peptides using a phenol sulfuric acid assay, and characterized the glycopeptides by N-terminal sequencing, amino acid analyses, or LC/MSMS. To determine the average number of sialic acid attachments per N-glycosylation, we digested Dsp with glycopeptidase A, labeled the released N-glycosylations with 2-aminobenzoic acid, and quantified the moles of released glycosylations by comparison to labeled standards of known concentration. Sialic acid was released by sialidase digestion and quantified by measuring β-NADH reduction of pyruvic acid, which was generated stoichiometrically from sialic acid by aldolase. To determine its forms, sialic acid released by sialidase digestion was labeled with 1,2-diamino-4,5-methyleneoxybenzene (DMB and compared to a DMB-labeled sialic acid reference panel by RP-HPLC. To determine the composition of Dsp glycosaminoglycan (GAG attachments, we digested Dsp with chondroitinase ABC and compared the chromotagraphic profiles of the released disaccharides to commercial standards. N-glycosylations were identified at Asn37, Asn77, Asn136, Asn155, Asn161, and Asn176. Dsp averages one sialic acid per N-glycosylation, which is always in the form of N-acetylneuraminic acid. O-glycosylations were

  2. Development of Antibody-Coated Magnetite Nanoparticles for Biomarker Immobilization

    Directory of Open Access Journals (Sweden)

    Christian Chapa Gonzalez

    2014-01-01

    Full Text Available Magnetic nanoparticles (MNPs have great potential in biomedical applications because of their magnetic response offers the possibility to direct them to specific areas and target biological entities. Magnetic separation of biomolecules is one of the most important applications of MNPs because their versatility in detecting cancer biomarkers. However, the effectiveness of this method depends on many factors, including the type of functionalization onto MNPs. Therefore, in this study, magnetite nanoparticles have been developed in order to separate the 5′-nucleotidase enzyme (5eNT. The 5eNT is used as a bio-indicator for diagnosing diseases such as hepatic ischaemia, liver tumor, and hepatotoxic drugs damage. Magnetic nanoparticles were covered in a core/shell type with silica, aminosilane, and a double shell of silica-aminosilane. A ScFv (fragment antibody and anti-CD73 antibody were attached to the coated nanoparticles in order to separate the enzyme. The magnetic separation of this enzyme with fragment antibody was found to be 28% higher than anti-CD73 antibody and the enzyme adsorption was improved with the double shell due to the increased length of the polymeric chain. Magnetite nanoparticles with a double shell (silica-aminosilane were also found to be more sensitive than magnetite with a single shell in the detection of biomarkers.

  3. Intra-spike crosslinking overcomes antibody evasion by HIV-1.

    Science.gov (United States)

    Galimidi, Rachel P; Klein, Joshua S; Politzer, Maria S; Bai, Shiyu; Seaman, Michael S; Nussenzweig, Michel C; West, Anthony P; Bjorkman, Pamela J

    2015-01-29

    Antibodies developed during HIV-1 infection lose efficacy as the viral spike mutates. We postulated that anti-HIV-1 antibodies primarily bind monovalently because HIV's low spike density impedes bivalent binding through inter-spike crosslinking, and the spike structure prohibits bivalent binding through intra-spike crosslinking. Monovalent binding reduces avidity and potency, thus expanding the range of mutations permitting antibody evasion. To test this idea, we engineered antibody-based molecules capable of bivalent binding through intra-spike crosslinking. We used DNA as a "molecular ruler" to measure intra-epitope distances on virion-bound spikes and construct intra-spike crosslinking molecules. Optimal bivalent reagents exhibited up to 2.5 orders of magnitude increased potency (>100-fold average increases across virus panels) and identified conformational states of virion-bound spikes. The demonstration that intra-spike crosslinking lowers the concentration of antibodies required for neutralization supports the hypothesis that low spike densities facilitate antibody evasion and the use of molecules capable of intra-spike crosslinking for therapy or passive protection. PMID:25635457

  4. Antibody-functionalized porous silicon nanoparticles for vectorization of hydrophobic drugs.

    Science.gov (United States)

    Secret, Emilie; Smith, Kevin; Dubljevic, Valentina; Moore, Eli; Macardle, Peter; Delalat, Bahman; Rogers, Mary-Louise; Johns, Terrance G; Durand, Jean-Olivier; Cunin, Frédérique; Voelcker, Nicolas H

    2013-05-01

    We describe the preparation of biodegradable porous silicon nanoparticles (pSiNP) functionalized with cancer cell targeting antibodies and loaded with the hydrophobic anti-cancer drug camptothecin. Orientated immobilization of the antibody on the pSiNP is achieved using novel semicarbazide based bioconjugate chemistry. To demonstrate the generality of this targeting approach, the three antibodies MLR2, mAb528 and Rituximab are used, which target neuroblastoma, glioblastoma and B lymphoma cells, respectively. Successful targeting is demonstrated by means of flow cytometry and immunocytochemistry both with cell lines and primary cells. Cell viability assays after incubation with pSiNPs show selective killing of cells expressing the receptor corresponding to the antibody attached on the pSiNP.

  5. Structural Basis for Broad and Potent Neutralization of HIV-1 by Antibody VRC01

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Tongqing; Georgiev, Ivelin; Wu, Xueling; Yang, Zhi-Yong; Dai, Kaifan; Finzi, Andrés; Kwon, Young Do; Scheid, Johannes F.; Shi, Wei; Xu, Ling; Yang, Yongping; Zhu, Jiang; Nussenzweig, Michel C.; Sodroski, Joseph; Shapiro, Lawrence; Nabel, Gary J.; Mascola, John R.; Kwong, Peter D. (NIH); (Rockefeller); (DFCI)

    2010-08-26

    During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

  6. [Locator or ball attachment: a guide for clinical decision making].

    Science.gov (United States)

    Büttel, Adrian E; Bühler, Nico M; Marinello, Carlo P

    2009-01-01

    Various attachments are available to retain overdentures on natural roots or implants. Technical aspects, the clinical handling, the capability to adapt or repair and the costs are parameters to be considered when choosing the appropriate attachment. Ball attachments and bars are clinically established and well documented. Ball attachments as prefabricated, unsplinted units are easily replaceable and show hygienic advantages, while bars show favorable stability. The Locator is a newer, popular clinical alternative to these established attachments. The ball attachment and the Locator are compared from a technical and clinical point of view. PMID:19852208

  7. [Locator or ball attachment: a guide for clinical decision making].

    Science.gov (United States)

    Büttel, Adrian E; Bühler, Nico M; Marinello, Carlo P

    2009-01-01

    Various attachments are available to retain overdentures on natural roots or implants. Technical aspects, the clinical handling, the capability to adapt or repair and the costs are parameters to be considered when choosing the appropriate attachment. Ball attachments and bars are clinically established and well documented. Ball attachments as prefabricated, unsplinted units are easily replaceable and show hygienic advantages, while bars show favorable stability. The Locator is a newer, popular clinical alternative to these established attachments. The ball attachment and the Locator are compared from a technical and clinical point of view.

  8. Implications of attachment theory for developmental psychopathology.

    Science.gov (United States)

    Sroufe, L A; Carlson, E A; Levy, A K; Egeland, B

    1999-01-01

    Bowlby's attachment theory is a theory of psychopathology as well as a theory of normal development. It contains clear and specific propositions regarding the role of early experience in developmental psychopathology, the importance of ongoing context, and the nature of the developmental process underlying pathology. In particular, Bowlby argued that adaptation is always the joint product of developmental history and current circumstances (never either alone). Early experience does not cause later pathology in a linear way; yet, it has special significance due to the complex, systemic, transactional nature of development. Prior history is part of current context, playing a role in selection, engagement, and interpretation of subsequent experience and in the use of available environmental supports. Finally, except in very extreme cases, early anxious attachment is not viewed as psychopathology itself or as a direct cause of psychopathology but as an initiator of pathways probabilistically associated with later pathology. PMID:10208353

  9. DFB laser with attached external intensity modulator

    Energy Technology Data Exchange (ETDEWEB)

    Marcuse, D. (AT and T Bell Labs. Holmdel, NJ (US))

    1990-02-01

    This paper presents a theoretical study of the frequency pulling effect exerted on a DFB laser by an external amplitude modulator that is directly attached to it. The modulator consists of a piece of waveguide whose loss is modulated by means of an externally applied voltage. The modulator affects the laser due to residual reflections from its far end which appear as a variable effective reflectivity to the output end of the DFB laser. Modulation affects the magnitude as well as the phase of the effective reflection coefficient presented to the laser due to the coupling of the real and imaginary parts of the effective refractive index of the modulator waveguide. The tuning problem is formulated as an eigenvalue equation for the DFB laser in the presence of an externally attached lossy cavity.

  10. Conflict in close relationships: an attachment perspective.

    Science.gov (United States)

    Simpson, J A; Rholes, W S; Phillips, D

    1996-11-01

    This study investigated how perceptions of current dating partners and relationships change after people with different attachment orientations attempt to resolve a problem in their relationship. Dating couples were videotaped while they tried to resolve either a major or a minor problem. Confirming predictions from attachment theory, men and women who had a more ambivalent orientation perceived their partner and relationship in relatively less positive terms after discussing a major problem. Observer ratings revealed that more ambivalent women who tried to resolve a major problem displayed particularly strong stress and anxiety and engaged in more negative behaviors. Conversely, men with a more avoidant orientation were rated as less warm and supportive, especially if they discussed a major problem. These results are discussed in terms of how highly ambivalent and highly avoidant people differentially perceive and respond to distressing events.

  11. [Set of radiocirculographic attachments for radioisotope laboratories].

    Science.gov (United States)

    Devishev, M I; Panfilova, N P; Ostrogradskaia, M G

    1980-01-01

    A set of radiocirculographic attachments is offered which serves for calibration and verification of readings taken from the apparatus during radiographic procedures. The set is designed for operation with all colimators of radiocirculographs produced in the USSR and Hungarian People's Republic. The set is able to imitate the investigation geometry, accumulation of radioactivity in the organ under study, absorption and scattering of radioactivty in the organism tissues. Series production of this device has already been initiated. PMID:7392870

  12. Preferential attachment in the protein network evolution

    OpenAIRE

    Eisenberg, Eli; Levanon, Erez Y.

    2003-01-01

    The Saccharomyces cerevisiae protein-protein interaction map, as well as many natural and man-made networks, shares the scale-free topology. The preferential attachment model was suggested as a generic network evolution model that yields this universal topology. However, it is not clear that the model assumptions hold for the protein interaction network. Using a cross genome comparison we show that (a) the older a protein, the better connected it is, and (b) The number of interactions a prote...

  13. Attachment of Thiobacillus thiooxidans to sulfur crystals.

    Science.gov (United States)

    SCHAEFFER, W I; HOLBERT, P E; UMBREIT, W W

    1963-01-01

    Schaeffer, W. I. (Rutgers, The State University, New Brunswick, N.J.), P. E. Holbert, and W. W. Umbreit. Attachment of Thiobacillus thiooxidans to sulfur crystals. J. Bacteriol. 85:137-140. 1963.-Electron micrographs of replicas of sulfur crystals before and after attack by Thiobacillus thiooxidans show that the microorganisms erode the crystal in the area immediately adjacent to the cell. When there are many cells, the entire crystal surface appears eroded.

  14. Attachment alternatives in implant-supported overdentures

    OpenAIRE

    Aktaş, Güliz; CANAY, Şenay

    2015-01-01

    Severe resorption of the alveolar ridges often makes it very difficult for patients to wear conventional dentures due to the lack of retention and stability of the dentures. Implant-supported overdentures offer edentulous patients a better retained and more stable prosthesis resulting in improved chewing ability and patient satisfaction compared against conventional complete dentures. There exist various attachment systems to be used with overdenture prostheses and are available in the market...

  15. Discriminant validity of the adult attachment interview.

    Science.gov (United States)

    Crowell, J A; Waters, E; Treboux, D; O'Connor, E O; Colon-Downs, C; Feider, O; Golby, B; Posada

    1996-10-01

    The Adult Attachment Interview is a semi-structured interview developed to investigate adults' attachment representations. Subjects are asked to describe their parents as caregivers, explain these descriptions, describe how their parents typically responded to distress, and discuss their current relationships with their parents. They are also asked to describe any significant losses and/or instances of abuse during childhood. Scoring focuses on the accessibility of early experiences to memory and the coherence and plausibility of the subject's narrative. Discriminant validity is always an important issue with such measures because IQ and other cognitively loaded variables offer plausible alternative interpretations or represent important correlates that should be treated as covariates when the measure is used. In addition, complex, multifaceted interviews always pose the risk of assessing general social adjustment rather than a more narrowly defined construct. This study examines the discriminant validity of the AAI vis(-)à-vis intelligence, social desirability, discourse style, and general social adjustment in a sample of 53 native-English-speaking, married women with preschool children. They were assessed with the AAI, a written IQ test, the Social Adjustment Scale, the Employment Experience Interview (discourse style), and a measure of social desirability. There were modest but significant correlations with IQ scores and social adjustment. There was no relation between AAI classifications and discourse style or social desirability. These results substantially strengthen the case for interpreting the AAI as an attachment-related measure.

  16. Cladding Attachment Over Thick Exterior Insulating Sheathing

    Energy Technology Data Exchange (ETDEWEB)

    Baker, P. [Building Science Corporation, Somerville, MA (United States); Eng, P. [Building Science Corporation, Somerville, MA (United States); Lepage, R. [Building Science Corporation, Somerville, MA (United States)

    2014-01-01

    The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of both wood framed walls as well as mass masonry wall assemblies. For thick layers of exterior insulation (levels greater than 1.5 inches), the use of wood furring strips attached through the insulation back to the structure has been used by many contractors and designers as a means to provide a convenient cladding attachment location (Straube and Smegal 2009, Pettit 2009, Joyce 2009, Ueno 2010). The research presented in this report is intended to help develop a better understanding of the system mechanics involved and the potential for environmental exposure induced movement between the furring strip and the framing. BSC sought to address the following research questions: 1.What are the relative roles of the mechanisms and the magnitudes of the force that influence the vertical displacement resistance of the system? 2.Can the capacity at a specified deflection be reliably calculated using mechanics based equations? 3.What are the impacts of environmental exposure on the vertical displacement of furring strips attached directly through insulation back to a wood structure?

  17. Cladding Attachment Over Thick Exterior Insulating Sheathing

    Energy Technology Data Exchange (ETDEWEB)

    Baker, P.; Eng, P.; Lepage, R.

    2014-01-01

    The addition of insulation to the exterior of buildings is an effective means of increasing the thermal resistance of both wood framed walls as well as mass masonry wall assemblies. For thick layers of exterior insulation (levels greater than 1.5 inches), the use of wood furring strips attached through the insulation back to the structure has been used by many contractors and designers as a means to provide a convenient cladding attachment location (Straube and Smegal 2009, Pettit 2009, Joyce 2009, Ueno 2010). The research presented in this report is intended to help develop a better understanding of the system mechanics involved and the potential for environmental exposure induced movement between the furring strip and the framing. BSC sought to address the following research questions: 1. What are the relative roles of the mechanisms and the magnitudes of the force that influence the vertical displacement resistance of the system? 2. Can the capacity at a specified deflection be reliably calculated using mechanics based equations? 3. What are the impacts of environmental exposure on the vertical displacement of furring strips attached directly through insulation back to a wood structure?

  18. Integrin Expression Regulates Neuroblastoma Attachment and Migration

    Directory of Open Access Journals (Sweden)

    Amy Meyer

    2004-07-01

    Full Text Available Neuroblastoma (NBL is the most common malignant disease of infancy, and children with bone metastasis have a mortality rate greater than 90%. Two major classes of proteins, integrins and growth factors, regulate the metastatic process. We have previously shown that tumorigenic NBL cells express higher levels of the type I insulin-like growth factor receptor (IGF-IR and that β1 integrin expression is inversely proportional to tumorigenic potential in NBL. In the current study, we analyze the effect of β1 integrin and IGF-IR on NBL cell attachment and migration. Nontumorigenic S-cells express high levels of β1 integrin, whereas tumorigenic N-cells express little β1 integrin. Alterations in (3, integrin are due to regulation at the protein level, as translation is decreased in N-type cells. Moreover, inhibition of protein synthesis shows that β1 integrin is degraded more slowly in S-type cells (SHEP than in N-type cells (SH-SY5Y and IMR32. Inhibition of α5β1 integrin prevents SHEP (but not SH-SY5Y or IMR32 cell attachment to fibronectin and increases SHEP cell migration. Increases in IGF-IR decrease β1 integrin expression, and enhance SHEP cell migration, potentially through increased expression of αvβ3. These data suggest that specific classes of integrins in concert with IGF-IR regulate NBL attachment and migration.

  19. Maternal anxiety, maternal sensitivity, and attachment.

    Science.gov (United States)

    Stevenson-Hinde, Joan; Chicot, Rebecca; Shouldice, Anne; Hinde, Camilla A

    2013-01-01

    Previous research has related maternal anxiety to insecurity of attachment. Here we ask whether different aspects of maternal sensitivity mediate this link. From a community sample of intact families with 1-3 children, mothers with 4.5-year-olds were selected for low, medium, or high anxiety levels (N = 98). Following Mary Ainsworth's lead, our maternal sensitivity measures were primarily based on ratings of direct observations. Six sets of measures were obtained: positive maternal style at home (a mean of four different ratings); providing a sensitive framework, limit setting, allowing autonomy, criticizing/cutting in (each a mean over two laboratory joint tasks); and tension-making (a mean of three different ratings in a fear-inducing task). Regression analyses showed firstly that maternal anxiety rather than behavioral inhibition or sex of child was the significant predictor of each maternal sensitivity measure; and secondly that these measures rather than maternal anxiety or sex were the significant predictors of security of attachment. Finally, ANOVA's indicated which sets of maternal ratings were associated with each pattern of attachment (Avoidant, Secure, Ambivalent, or Controlling).

  20. Machiavellianism and Parental Attachment in Adolescence

    Directory of Open Access Journals (Sweden)

    András Láng

    2015-02-01

    Full Text Available Machiavellianism is a well-studied topic in several branches of psychology. Still, it has received little attention from a developmental perspective. Previous retrospective studies linked Machiavellianism to poor parental care, but actual reports of adolescents who live in their family of origin have been ignored so far. Therefore, we investigated the relationship between Machiavellianism and parental attachment in adolescence and possible sex differences based on life history theory. An adolescent sample (N = 376; 17.27 ± .77 years of age completed the Mach-IV and the maternal and paternal versions of revised Inventory of Parent and Peer Attachment (IPPA-R. According to our results, significant sex differences emerged in the relationship between Machiavellianism and attachment to parents. For girls, maternal alienation proved to be the only significant predictor of Machiavellianism, whereas for boys, low intensity and quality of verbal communication with father predicted higher levels of Machiavellianism. Results are discussed from an evolutionary perspective of socialization and from the perspective of emotion regulation.

  1. Antibody responses to recombinant and plasma derived hepatitis B vaccines.

    OpenAIRE

    Brown, S E; Stanley, C.; Howard, C. R.; Zuckerman, A J; Steward, M W

    1986-01-01

    The antibody response to hepatitis B surface antigen (anti-HBs) induced in 25 recipients of a recombinant hepatitis B vaccine derived from yeast was compared with that induced in 25 recipients of a vaccine prepared from hepatitis B surface antigen (HBsAg) derived from plasma. Anti-HBs affinity and specificity were compared using assays of antibody affinity with two different antigens, a complex of the major polypeptide of HBsAg (p25; molecular weight 25 000 daltons) covalently linked to its g...

  2. Analysis of sperm membrane antigens relevant to antisperm antibody using Western blot

    Institute of Scientific and Technical Information of China (English)

    WangHF

    2002-01-01

    Objective:To identify the sperm membrane antigens associated with antisperm antibody.Methods:The antisperm antibody in serum was tested by ELISA.Antisperm antibody positive sera from 18 infertile men and 15 infertile women were used.The molecular weight(MW) of sperm membrane antigens associated with the antisperm antibody was analyzed with antisperm antibody positive serum using Western blot.Results:Eight kinds of MW of sperm membrane antigens were identified.The ratio of identification on the 78 KD(60.7%),60KD(71.4%),51KD(14.9%) and 23KD(14.29%)sperm antigen was higher than other.Conclusion:sperm membrane antigens with MW of 78KD,60KD,51KD and 23KD were associated with antisperm antibody and immunological infertility.

  3. Lineage tracing of human B cells reveals the in vivo landscape of human antibody class switching.

    Science.gov (United States)

    Horns, Felix; Vollmers, Christopher; Croote, Derek; Mackey, Sally F; Swan, Gary E; Dekker, Cornelia L; Davis, Mark M; Quake, Stephen R

    2016-01-01

    Antibody class switching is a feature of the adaptive immune system which enables diversification of the effector properties of antibodies. Even though class switching is essential for mounting a protective response to pathogens, the in vivo patterns and lineage characteristics of antibody class switching have remained uncharacterized in living humans. Here we comprehensively measured the landscape of antibody class switching in human adult twins using antibody repertoire sequencing. The map identifies how antibodies of every class are created and delineates a two-tiered hierarchy of class switch pathways. Using somatic hypermutations as a molecular clock, we discovered that closely related B cells often switch to the same class, but lose coherence as somatic mutations accumulate. Such correlations between closely related cells exist when purified B cells class switch in vitro, suggesting that class switch recombination is directed toward specific isotypes by a cell-autonomous imprinted state. PMID:27481325

  4. Development of radioactivity labelling method of new antibody by using the antibody engineering

    International Nuclear Information System (INIS)

    With an aim to develop a method to produce labelled antibodies with low immunogenicity, two recombinant fusion proteins; scFv-His and scFv-MTβ were produced using gene engineering techniques. The former was constructed with scFv-antibody and histidine hexamer, a metal-chelated protein (or peptide). The latter was done with scFv-antibody and β-domain of metallothionein. Then, antigen-binding activity and metal-binding activity of these fusion proteins were determined using gel-filtration chromatography and ELISA. The main antigen-binding activity of scFv-His preparation was detected in a domain of about 25-30 kDa, which agreed with the peak of 29 kDa corresponding to the presumed molecular weight for the protein. Whereas the antigen-binding activity of scFv-MTβ was found in a domain of 30-35 kDa, which agreed with 32 kDa, the presumed molecular weight of scFv-MTβ. Gel-filtration chromatography of scFv-His preparation after the addition of Cu2+ ion revealed an optical absorption at 280 nm and a Cu-peak near at 14 kDa. These results suggested that the metal affinity of the histidine-hexamer was too weak to chelate Cu2+ in a solution. The chromatography of scFv-MTβ preparation added with Cd2+ showed a peak of Cd appeared around a position of about 20 kDa but the peak was not coincident with that of the antigen-binding activity (ca. 30 kDa), suggesting that the present preparation of scFv-MTβ had no Cd-binding activity due to metal-exchange reaction. Based on these results, problems on the production of recombinant scFv-antibody fused with metal-binding domain of cystein-binding type or histidine-binding one were discussed. (M.N.)

  5. Targeting of Antibodies using Aptamers

    OpenAIRE

    Missailidis, Sotiris

    2003-01-01

    The chapter presents a methodology for the rapid selection of aptamers against antibody targets. It is a detailed account of the various methodological steps that describe the selection of aptamers, including PCR steps, buffers to be used, target immobilisation, partitioning and amplification of aptamers, clonning and sequencing, to results in high affinity and specificity ligands for the chosen target antibody.

  6. Structural Characterization of Peptide Antibodies

    DEFF Research Database (Denmark)

    Chailyan, Anna; Marcatili, Paolo

    2015-01-01

    The role of proteins as very effective immunogens for the generation of antibodies is indisputable. Nevertheless, cases in which protein usage for antibody production is not feasible or convenient compelled the creation of a powerful alternative consisting of synthetic peptides. Synthetic peptide...

  7. Pathogenic role of antiphospholipid antibodies

    NARCIS (Netherlands)

    Salmon, J. E.; de Groot, P. G.

    2008-01-01

    The antiphospholipid antibody syndrome (APS) is characterized by recurrent arterial and venous thrombosis and/or pregnancy in association with antiphospholipid (aPL) antibodies. The pathogenic mechanisms in APS that lead to in vivo injury are incompletely understood. Recent evidence suggests that AP

  8. Directed Selection of Recombinant Human Monoclonal Antibodies to Herpes Simplex Virus Glycoproteins from Phage Display Libraries

    Science.gov (United States)

    Sanna, Pietro Paolo; Williamson, R. Anthony; de Logu, Alessandro; Bloom, Floyd E.; Burton, Dennis R.

    1995-07-01

    Human monoclonal antibodies have considerable potential in the prophylaxis and treatment of viral disease. However, only a few such antibodies suitable for clinical use have been produced to date. We have previously shown that large panels of human recombinant monoclonal antibodies against a plethora of infectious agents, including herpes simplex virus types 1 and 2, can be established from phage display libraries. Here we demonstrate that facile cloning of recombinant Fab fragments against specific viral proteins in their native conformation can be accomplished by panning phage display libraries against viral glycoproteins "captured" from infected cell extracts by specific monoclonal antibodies immobilized on ELISA plates. We have tested this strategy by isolating six neutralizing recombinant antibodies specific for herpes simplex glycoprotein gD or gB, some of which are against conformationally sensitive epitopes. By using defined monoclonal antibodies for the antigen-capture step, this method can be used for the isolation of antibodies to specific regions and epitopes within the target viral protein. For instance, monoclonal antibodies to a nonneutralizing epitope can be used in the capture step to clone antibodies to neutralizing epitopes, or antibodies to a neutralizing epitope can be used to clone antibodies to a different neutralizing epitope. Furthermore, by using capturing antibodies to more immunodominant epitopes, one can direct the cloning to less immunogenic ones. This method should be of value in generating antibodies to be used both in the prophylaxis and treatment of viral infections and in the characterization of the mechanisms of antibody protective actions at the molecular level.

  9. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed. PMID:20930555

  10. Metrics for antibody therapeutics development.

    Science.gov (United States)

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  11. Ion Momentum Imaging of Dissociative Electron Attachment to Small Molecules

    Science.gov (United States)

    Fogle, Michael

    2015-09-01

    In recent years, low energy dissociative electron attachment (DEA) interactions have been of interest to varying biological and technological applications. To study the dynamics resulting from DEA, we used an ion-momentum imaging apparatus based on the Cold Target Recoil Ion Momentum Spectroscopy (COLTRIMS) technique in which a molecular beam is crossed by a pulsed electron beam. The beam interaction takes place in a 4 π pulsed electrostatic spectrometer that collects the anion fragments resulting from DEA. The molecular beam is formed by a supersonic expansion which results in a well-localized and cold target. Using this apparatus we have investigated the DEA dynamics for several small molecules: CO2 at the 4 eV shape resonance and the 8 eV Feshbach resonance; N2O at the 2.3 eV shape resonance; HCCH at the 3 eV shape resonance; and CF4 near the 7 eV resonance. An overview of these experimental ion-momentum results will be compared to ab initio electronic structure and fixed-nuclei scattering calculations to gauge the resulting dynamics driven by DEA. In many cases, conical intersections play a pivotal role in driving the dynamics. Some of these systems exhibit non-axial recoil conditions indicative of a bending dynamics in the transitory negative ion state while others exhibit a direct axial recoil dissociation without any bending. This work is supported by the National Science Foundation under Contract NSF-PHYS1404366.

  12. 多疣壁虎tubulin beta 3基因克隆和多克隆抗体制备%Molecular cloning of tubulin beta 3 (TUBB3) in Gekkojaponicus and preparation of its polyclonal antibody

    Institute of Scientific and Technical Information of China (English)

    李静; 秦勇; 顾云; 刘炎; 刘梅

    2012-01-01

    The tubulin beta III (TUBB3) gene encodes a class III member of the beta tubulin protein family that is primarily expressed in neurons and is considered to play a critical role in proper axon guidance and maintenance. This protein is generally used as a specific marker of neurons in the central nervous system. We obtained the full length cDNA sequence of TUBB3 by using the RACE method based on the EST fragment from the brain and spinal cord cDNA library of Gekko japonicus. We further investigated the multi-tissue expression pattern by RT-PCR and identified one transcript of TUBB3 about 1.8 kb in the central nervous system of Gekko japonicus by Northern blotting. The completed cDNA of gecko TUBB3 is 1790 bp with an open reading frame of 1350 bp, encoding a 450 amino-acid protein. The recombinant plasmid of pET-32a-TUBB3 was constructed and induced to express His-tagged TUBB3 protein in prokaryotic BL21 cells. The purified TUBB3 protein was then used to immunize rabbits to generate polyclonal antisera. The titer of the antiserum was more than 1:65 536 determined by ELISA. The result of western blotting showed that the TUBB3 antibody could specifically recognize the recombinant TUBB3 protein and endogenous TUBB3 protein. Our findings provide the tools to further understand the TUBB3 gene and investigate the regeneration of the central nervous system in Gekko japonicas.%Tubulin beta 3 (TUBB3)是特异表达于神经元的微管蛋白tubulin beta家族成员,被认为在维持轴突正常状态起着重要作用,是神经元特异的标志蛋白.该研究旨在获得多疣壁虎TUBB3全长cDNA序列并制备其多克隆抗体,为进一步研究多疣壁虎断尾再生提供基因和抗体工具.根据多疣壁虎中枢神经组织cDNA文库中TUBB3的EST片段序列,采用RACE-PCR方法,获得了全长cDNA,序列全长1790 bp,编码450个氨基酸,与其他物种TUBB3蛋白高度同源;RT-PCR方法和Northern blotting检测了TUBB3组织表达谱及其转录本的大

  13. Dual-shank attachment design for omega seals

    Science.gov (United States)

    Sattinger, Stanley S.

    1978-01-01

    An improved apparatus and process for attaching welded omega seal segments to reactor heads, standpipes, mechanisms, and plugs comprises a first shank in combination with a second shank to attach an omega seal at a metal-to-metal interface.

  14. Continuities and changes in infant attachment patterns across two generations.

    Science.gov (United States)

    Raby, K Lee; Steele, Ryan D; Carlson, Elizabeth A; Sroufe, L Alan

    2015-01-01

    This study examined the intergenerational continuities and changes in infant attachment patterns within a higher-risk longitudinal sample of 55 female participants born into poverty. Infant attachment was assessed using the Strange Situation when participants were 12 and 18 months as well as several decades later with participants' children. Paralleling earlier findings from this sample on the stability of attachment patterns from infancy to young adulthood, results provided evidence for intergenerational continuities in attachment disorganization but not security. Children of adults with histories of infant attachment disorganization were at an increased risk of forming disorganized attachments. Although changes in infant attachment patterns across the two generations were not correlated with individuals' caregiving experiences or interpersonal stresses and supports during childhood and adolescence, higher quality social support during adulthood was associated with intergenerational changes from insecure to secure infant-caregiver attachment relationships. PMID:26213155

  15. Structure of the Ebola virus glycoprotein bound to a human survivor antibody

    OpenAIRE

    Lee, Jeffrey E.; Fusco, Marnie L.; Hessell, Ann J.; Oswald, Wendelien B; Burton, Dennis R.; Saphire, Erica Ollmann

    2008-01-01

    Ebola virus (EBOV) entry requires the surface glycoprotein, GP, to initiate attachment and fusion of viral and host membranes. Here, we report the crystal structure of EBOV GP in its trimeric, pre-fusion conformation (GP1+GP2) bound to a neutralizing antibody, KZ52, derived from a human survivor of the 1995 Kikwit outbreak. Three GP1 viral attachment subunits assemble to form a chalice, cradled by the GP2 fusion subunits, while a novel glycan cap and projected mucin-like domain restrict acces...

  16. HIV Molecular Immunology 2014

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Korber, Bette Tina Marie [Los Alamos National Lab. (LANL), Los Alamos, NM (United States); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States); Koup, Richard [Vaccine Research Center National Institutes of Health (United States); de Boer, Rob [Utrecht Univ. (Netherlands). Dept. of Biology; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Brander, Christian [Institucioi Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Walker, Bruce D. [Ragon Institute of Massachusetts General Hospital, Cambridge, MA (United States); Harvard Univ., Cambridge, MA (United States); Massachusetts Inst. of Technology (MIT), Cambridge, MA (United States)

    2015-02-03

    HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2014 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as crossreactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins are provided.

  17. Attachment dimensions as a predictor of emotional intelligence and sociability.

    OpenAIRE

    Svensson, Helen

    2011-01-01

    One of the ways in which the attachment relationships we develop during infancy influence us throughout life is by emotion regulation. Although studies have shown that attachment orientations affect emotional functioning, the effect of attachment dimensions on overall emotional functioning and sociability has still not been investigated. The purpose of the present study was to examine if attachment dimensions predict emotional intelligence (EI) and sociability. The sample consisted of 75 psyc...

  18. Attachment at work: its construct, discriminant, and predictive validity.

    OpenAIRE

    Neustadt, E.

    2007-01-01

    This dissertation is concerned with Attachment Theory (e.g. Bowlby, 1969/82 1973 1980) as it may apply to adults at work, with particular attention to the bearing of attachment orientation on management style and job performance. Chapter 1 provides an overview of attachment theory, existing measures and salient measurement issues Chapter 2 examines the literature, with a particular focus on adult attachment. Chapters 3-9 present a series of studies that entail testing the construct, discrimin...

  19. The Association between State Attachment Security and State Mindfulness

    OpenAIRE

    Pepping, Christopher A.; Penelope J Davis; Analise O'Donovan

    2015-01-01

    Recent research suggests that attachment and mindfulness are related, though the nature of this association is unclear. Here we present two studies examining whether there is a causal relationship between state attachment and state mindfulness. Study 1 investigated the effects of experimentally increasing state mindfulness on state attachment security. State mindfulness was successfully enhanced, but this led to no change in state attachment security. Study 2 investigated the effects of exper...

  20. Examinations on retention of overdentures with elastic frictional attachments

    OpenAIRE

    W. Chladek; G. Chladek; M. Wrzuś-Wieliński; J. Żmudzki

    2010-01-01

    frictional attachments.Design/methodology/approach: The examinations of retention characteristics of traditional attachments, elastic frictional attachments and models of overdentures have been carried out using Zwick testing machine. Retention forces and work essential for separating the attachments have been determined as well. Next the force – displacement characteristics for overdenture model have been registered for two places where the force was applied and for three inclination angles ...

  1. Disrupted caring attachments: implications for long-term care.

    Science.gov (United States)

    Flannery, Raymond B

    2002-01-01

    Caring attachments or social supports are the positive psychological and physical contacts and relationships between people. These attachments have been associated with improved health, well-being, and longevity. It is also true that disrupted caring attachments are associated with impaired health and well-being. This paper reviews the general medical and elder medical findings of disrupted caring attachments and negative health outcomes. The implications of these findings for dementia sufferers, caregivers, and long-term care staff are examined.

  2. Adult Attachment Ratings (AAR): An Item Response Theory Analysis

    OpenAIRE

    Pilkonis, Paul A.; Kim, Yookyung; Yu, Lan; Morse, Jennifer Q.

    2013-01-01

    The Adult Attachment Ratings (AAR) include 3 scales for anxious, ambivalent attachment (excessive dependency, interpersonal ambivalence, and compulsive care-giving), 3 for avoidant attachment (rigid self-control, defensive separation, and emotional detachment), and 1 for secure attachment. The scales include items (ranging from 6–16 in their original form) scored by raters using a 3-point format (0 = absent, 1 = present, and 2 = strongly present) and summed to produce a total score. Item resp...

  3. Adult attachment styles and the psychological response to infant bereavement

    OpenAIRE

    Shevlin, Mark; Boyda, David; Elklit, Ask; Murphy, Siobhan

    2014-01-01

    Background: Based on Bowlby’s attachment theory, Bartholomew proposed a four-category attachment typology by which individuals judged themselves and adult relationships. This explanatory model has since been used to help explain the risk of psychiatric comorbidity.Objective: The current study aimed to identify attachment typologies based on Bartholomew’s attachment styles in a sample of bereaved parents on dimensions of closeness/dependency and anxiety. In addition, it sought to assess the re...

  4. Structural Correspondence of the Oriented Attachment Growth Mechanism of Crystals of the Pharmaceutical Dirithromycin.

    Science.gov (United States)

    Liang, Zuozhong; Wang, Yuan; Wang, Wei; Han, Xianglong; Chen, Jian-Feng; Xue, Chunyu; Zhao, Hong

    2015-12-29

    The oriented attachment (OA) mechanism is promising for designing novel nanomaterials, yet an intensive understanding of the relationship between the crystal structure and attachment orientation is still lacking. In this work, we report layered hexagonal crystals of the pharmaceutical dirithromycin (DIR) containing multiple layers fabricated via a solvothermal method for a certain period of time at 40 °C. These elongated hexagonal crystals experience an OA that is preferentially on the face (001) of the initial crystals to assemble the final crystals into layered stacks. Through agreement with molecular modeling calculations, we predicted the final crystal growth morphology and confirmed the favored attachment surface based on the energy change ΔE following an OA event. These simulation results at the molecular level yielded good agreement with the crystal growth experiments. This study demonstrates the critical importance of combining experiments with a computational approach to understand the intrinsic molecular details of the OA growth mechanism of other compounds and to design nanomaterials with a desirable morphology and physical and chemical properties. PMID:26632998

  5. Proteomics Insights: Proteins related to Larval Attachment and Metamorphosis of Marine Invertebrates

    Directory of Open Access Journals (Sweden)

    KONDETHIMMANAHALLI eCHANDRAMOULI

    2014-10-01

    Full Text Available The transition in an animal from a pelagic larval stage to a sessile benthic juvenile typically requires major morphological and behavioral changes. Larval competency, attachment and initiation of metamorphosis are thought to be regulated by intrinsic chemical signals and specific sets of proteins. However, the molecular mechanisms that regulate larval attachment and metamorphosis in marine invertebrates have yet to be fully elucidated. Despite the many challenges associated with analysis of the larvae proteome, recent proteomic technologies have been used to address specific questions in larval developmental biology. These and other molecular studies have generated substantial amount of information of the proteins and molecular pathways involved in larval attachment and metamorphosis. Furthermore, the results of these studies have shown that systematic changes in protein expression patterns and post-translational modifications (PTM are crucial for the transition from larva to juvenile. The degeneration of larval tissues is mediated by protein degradation, while the development of juvenile organs may require PTM. In terms of application, the identified proteins may serve as targets for antifouling compounds, and biomarkers for environmental stressors. In this review we highlight the strengths and limitations of proteomic tools in the context of the study of marine invertebrate larval biology.

  6. Proteomics insights: proteins related to larval attachment and metamorphosis of marine invertebrates

    KAUST Repository

    Chandramouli, Kondethimmanahalli

    2014-10-31

    The transition in an animal from a pelagic larval stage to a sessile benthic juvenile typically requires major morphological and behavioral changes. Larval competency, attachment and initiation of metamorphosis are thought to be regulated by intrinsic chemical signals and specific sets of proteins. However, the molecular mechanisms that regulate larval attachment and metamorphosis in marine invertebrates have yet to be fully elucidated. Despite the many challenges associated with analysis of the larvae proteome, recent proteomic technologies have been used to address specific questions in larval developmental biology. These and other molecular studies have generated substantial amount of information of the proteins and molecular pathways involved in larval attachment and metamorphosis. Furthermore, the results of these studies have shown that systematic changes in protein expression patterns and post-translational modifications (PTMs) are crucial for the transition from larva to juvenile. The degeneration of larval tissues is mediated by protein degradation, while the development of juvenile organs may require PTM. In terms of application, the identified proteins may serve as targets for antifouling compounds, and biomarkers for environmental stressors. In this review we highlight the strengths and limitations of proteomic tools in the context of the study of marine invertebrate larval biology.

  7. Neurobiology of secure infant attachment and attachment despite adversity: a mouse model.

    Science.gov (United States)

    Roth, T L; Raineki, C; Salstein, L; Perry, R; Sullivan-Wilson, T A; Sloan, A; Lalji, B; Hammock, E; Wilson, D A; Levitt, P; Okutani, F; Kaba, H; Sullivan, R M

    2013-10-01

    Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7-9 or 13-14) with presentations of peppermint odor and either stroking or shock. We used (14) C 2-deoxyglucose (2-DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7-9 mice learned to prefer an odor following either odor-stroke or shock conditioning, whereas odor-shock conditioning at PN13-14 resulted in aversion/fear learning. 2-DG data indicated enhanced bulbar activity in PN7-9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13-14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment-related behaviors and behavioral development.

  8. From secure dependency to attachment: Mary Ainsworth's integration of Blatz's security theory into Bowlby's attachment theory.

    Science.gov (United States)

    van Rosmalen, Lenny; van der Horst, Frank C P; van der Veer, René

    2016-02-01

    John Bowlby is generally regarded as the founder of attachment theory, with the help of Mary Ainsworth. Through her Uganda and Baltimore studies Ainsworth provided empirical evidence for attachment theory, and she contributed the notion of the secure base and exploratory behavior, the Strange Situation Procedure and its classification system, and the notion of maternal sensitivity. On closer scrutiny, many of these contributions appear to be heavily influenced by William Blatz and his security theory. Even though Blatz's influence on Ainsworth has been generally acknowledged, this article, partly based on understudied correspondence from several personal archives, is the first to show which specific parts of attachment theory can be traced back directly to Blatz and his security theory. When Ainsworth started working with Bowlby in the 1950s, around the time he turned to evolutionary theory for an explanation of his findings, she integrated much of Blatzian security theory into Bowlby's theory in the making and used her theoretical and practical experience to enrich attachment theory. Even though Blatz is hardly mentioned nowadays, several of his ideas live on in attachment theory.

  9. Neurobiology of secure infant attachment and attachment despite adversity: a mouse model.

    Science.gov (United States)

    Roth, T L; Raineki, C; Salstein, L; Perry, R; Sullivan-Wilson, T A; Sloan, A; Lalji, B; Hammock, E; Wilson, D A; Levitt, P; Okutani, F; Kaba, H; Sullivan, R M

    2013-10-01

    Attachment to an abusive caregiver has wide phylogenetic representation, suggesting that animal models are useful in understanding the neural basis underlying this phenomenon and subsequent behavioral outcomes. We previously developed a rat model, in which we use classical conditioning to parallel learning processes evoked during secure attachment (odor-stroke, with stroke mimicking tactile stimulation from the caregiver) or attachment despite adversity (odor-shock, with shock mimicking maltreatment). Here we extend this model to mice. We conditioned infant mice (postnatal day (PN) 7-9 or 13-14) with presentations of peppermint odor and either stroking or shock. We used (14) C 2-deoxyglucose (2-DG) to assess olfactory bulb and amygdala metabolic changes following learning. PN7-9 mice learned to prefer an odor following either odor-stroke or shock conditioning, whereas odor-shock conditioning at PN13-14 resulted in aversion/fear learning. 2-DG data indicated enhanced bulbar activity in PN7-9 preference learning, whereas significant amygdala activity was present following aversion learning at PN13-14. Overall, the mouse results parallel behavioral and neural results in the rat model of attachment, and provide the foundation for the use of transgenic and knockout models to assess the impact of both genetic (biological vulnerabilities) and environmental factors (abusive) on attachment-related behaviors and behavioral development. PMID:23927771

  10. Attachment icebergs: Maternal and child health nurses' evaluation of infant-caregiver attachment.

    Science.gov (United States)

    Bryant, Edith; Ridgway, Lael; Lucas, Sandra

    2016-05-01

    Secure attachment of infants to their caregiver is important when promoting the emotional wellbeing and mental health of infants. Maternal and child health (MCH) nurses are well positioned to observe the quality of interactions between infants and caregivers and to assess and intervene. However, as yet there are no approved methods to assess the emotional and mental health of infants in community settings. A qualitative descriptive study of 12 MCH nurses in Victoria, Australia, using semi-structured interviews, was thematically analysed. The data revealed that nurses used many skills to identify and manage attachment difficulties. Key among these were observations of interactions, collaboration with caregivers and reflective practice. Assessments and interventions are also influenced by nurses' emotions, attitudes and workplace factors. An unexpected finding was that attachment markers can be likened to an 'iceberg': warning indicators at the tip can be easily observed by the nurse, while the less obvious underlying factors need to be explored in order to support attachment and improve infant mental health outcomes. Education for nurses should include concepts of attachment and link behaviours with emotional wellbeing. PMID:27276798

  11. Molecular bioengineering of biomaterials in the 1990s and beyond: a growing liaison of polymers with molecular biology.

    Science.gov (United States)

    Hoffman, A S

    1992-02-01

    An important trend in biomaterials research and development is the synthesis of polymers that combine capabilities of biologic recognition (biomimetic) with special physicochemical properties of the synthetic polymer system. Another important trend in such "molecular bioengineering" is to develop, perhaps via computer-aided molecular design, new artificial biomimetic systems by exact placement of functional groups on rigid polymer backbones, cross-linked structures, or macromolecular assemblies. In this way, biocatalytic functioning or biorecognition similar to enzymes and antibodies can be achieved without the inherent instability often encountered with the native biomolecules or assemblies. Perhaps the most exciting trend in biomaterials research and development is the availability of new biomolecules, e.g., via protein engineering and of hardy cells with specific biofunctions and bioresponses that can be tailored to specific medical or biotechnological needs. The wide variety of ways that such biomolecules and cells can be combined with polymeric biomaterials provides tremendously exciting opportunities for the biomaterials scientists and engineers. In addition to these synthetic approaches, new and exciting analytical tools, such as the scanning tunneling microscope and the atomic force microscope, are permitting study on a molecular scale of individual and small clusters of proteins and other biomolecular assemblies on surfaces. Cell attachments and spreading may also be visualized at various depths within the cell using the confocal laser microscope. Such analytical techniques can lead to important new knowledge about biologic interactions with biomaterials and, therefore, to development of even more biocompatible implants and devices. This paper overviews the present state of polymeric biomaterials and highlights the important and exciting opportunities generated by the liaison of these materials with molecular biology.

  12. Attachment Styles among Bullies, Victims and Uninvolved Adolescents

    Science.gov (United States)

    Koiv, Kristi

    2012-01-01

    Attachment theory provides a frame for understanding the role of attachment styles in the development of bullying behaviour in adolescence. The present study examined attachment styles (secure, avoidant and anxious/ambivalent) that differentiated bullies, victims, bully/victims and uninvolved adolescents. A total of 1,921 students (1,006 girls and…

  13. 49 CFR 583.9 - Attachment and maintenance of label.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Attachment and maintenance of label. 583.9 Section 583.9 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC... Attachment and maintenance of label. (a) Attachment of the label. (1) Except as provided in (a)(2),...

  14. 12 CFR 1511.8 - Notice of attachment.

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 7 2010-01-01 2010-01-01 false Notice of attachment. 1511.8 Section 1511.8....8 Notice of attachment. The interest of a debtor in a Security Entitlement may be reached by a... or other notice of attachment in any particular case or class of cases....

  15. Adolescents in Wilderness Therapy: A Qualitative Study of Attachment Relationships

    Science.gov (United States)

    Bettmann, Joanna E.; Olson-Morrison, Debra; Jasperson, Rachael A.

    2011-01-01

    Characterized by acute changes in attachment relationships, adolescence is a time of balancing autonomy and attachment needs. For adolescents in wilderness therapy programs, the setting often challenges their understanding of their own attachment relationships. The current study evaluates the narratives of 13 adolescents in a wilderness therapy…

  16. Predictive Implications of Secure Mother-Infant Attachments.

    Science.gov (United States)

    Hunt, Judith Lynn

    The general proposition of attachment theory is that attachment is grounded in an independent, biologically based system. The quality of primary attachment relationships strongly influences a child's early personality organization, particularly the concept of self and others. The theory emphasizes the primary status and biological function of…

  17. Attachment State of Mind: Implications for Adjustment to College

    Science.gov (United States)

    Bernier, Annie; Larose, Simon; Boivin, Michel; Soucy, Nathalie

    2004-01-01

    The main purpose of this study was to examine the associations between attachment state of mind and adjustment to college. A related aim was to examine the moderating role of attachment state of mind in the relation between parental control and school adjustment. One-hundred two college freshmen completed the Adult Attachment Interview and a…

  18. Parental Attachment and Identity in Portuguese Late Adolescents.

    Science.gov (United States)

    Matos, Paula Mena; Barbosa, Sonia; de Almeida, Helena Milheiro; Costa, Maria Emilia

    1999-01-01

    Based on life span attachment perspective and on identity status paradigm, this study investigated the relationship between attachment and identity in a sample of 361 Portuguese late adolescents as a function of parental and adolescent gender. The results indicated gender differences in the association between attachment variables and identity…

  19. Device and process for attachment of parts to rocket motors

    Science.gov (United States)

    Yagla, Jon J.; Lowry, Robert W.; Mears, Otho L.

    1992-04-01

    An attachment platform positioned longitudinally on a rocket motor chamber and secured with laser welding techniques is described. Each attachment platform is continuously sealed longitudinally to the rocket motor chamber through the application of laser welding and optical seam tracking. Application of laser welding techniques allows for repair and installation of attachment platforms on rocket motors fully loaded with live propellant.

  20. Photoswitchable method for the ordered attachment of proteins to surfaces

    Science.gov (United States)

    Camarero, Julio A.; DeYoreo, James J.; Kwon, Youngeun

    2011-07-05

    Described herein is a method for the attachment of proteins to any solid support with control over the orientation of the attachment. The method is extremely efficient, not requiring the previous purification of the protein to be attached, and can be activated by UV-light. Spatially addressable arrays of multiple protein components can be generated by using standard photolithographic techniques.

  1. Attachment Representations and Characteristics of Friendship Relations during Adolescence

    Science.gov (United States)

    Zimmermann, Peter

    2004-01-01

    Attachment theory proposes that experiences with the primary caregivers are an important basis for the development of close social relationships outside the parent-child relationship. This study examined the association between representations of attachment, as assessed with the Adult Attachment Interview (AAI), representations of friendship and…

  2. Anxious attachment may be a vulnerability factor for developing embitterment

    NARCIS (Netherlands)

    Blom, D.; Middendorp, H. van; Geenen, R.

    2012-01-01

    By predisposing to ego-defensive strategies in social situations, a negative attachment history may promote embitterment. The present study identified attachment anxiety - more than attachment avoidance - as a possible vulnerability factor for the development and maintenance of embitterment. This fa

  3. An Observational Measure of Children's Attachments to Soft Objects.

    Science.gov (United States)

    Steier, Alison J.; Lehman, Elyse Brauch

    2000-01-01

    Developed direct observational measure of children's attachment to inanimate objects such as blankets and soft toys among object-attached and non-object-attached 15- to 31-month-olds. Procedure varied arousal levels across situations. Found support for validity of the procedure in, among other factors, its ability to capture the preference of…

  4. Adult Attachment and Disordered Eating in Undergraduate Men and Women

    Science.gov (United States)

    Elgin, Jenna; Pritchard, Mary

    2006-01-01

    Previous research on gender differences between males and females on the risk factors leading to disordered eating is sparse, especially on males and eating disorders using attachment theory. This study examined the relationship between adult attachment style and disordered eating in men and women. Secure attachment scores were significantly…

  5. Magnetic antibody immunoassay (MAIA) - a new improved separation technique in radioimmunoassay

    International Nuclear Information System (INIS)

    Following a short description of the principle of radioimmunoassay and immunoradiometric assay, the special difficulties connected with the separation steps are discussed. Centrifugation is subject to inaccuracies and both time-consuming and technically complicated. Moreover it involves the risk of microbial or radioactive contamination. A new solid-phase procedure is presented using magnetizable particles as solid phase which are for instance bonded with the antibody. Separation is effected by collection of the magnetizable particles and the attached antibodies using a permanent magnet and subsequent decanting of the supernatant. The method is explained using two examples (cortisol, digoxin). (ZDE)

  6. Processes involved in client-nominated relationship building incidents: Client attachment, attachment to therapist, and session impact.

    Science.gov (United States)

    Janzen, Jennifer; Fitzpatrick, Marilyn; Drapeau, Martin

    2008-09-01

    Thirty volunteer clients of trainee therapists nominated an incident that was critical in the development of their therapeutic relationship. Clients completed the Client Attachment to Therapist Scale (CATS), the Experiences in Close Relationships Scale (ECRS), and the Session Impacts Scale (SIS). Clients reported an increase in attachment security with their therapists, along with perceptions of support and relief and increasing exploration following the relationship building incident. While clients' avoidant attachment was unrelated to attachment to the therapist prior to the incidents, in subsequent sessions avoidance was related to a change in secure attachment to therapist. Finally, client attachment to therapist but not general attachment was significantly related to in-session exploration. Findings are discussed in light of attachment theory and convergence with findings from the field of social psychology. (PsycINFO Database Record (c) 2010 APA, all rights reserved).

  7. Characterisation of a novel light activated adhesive scaffold: Potential for device attachment.

    Science.gov (United States)

    Ark, Morris; Boughton, Philip; Lauto, Antonio; Tran, Giang T; Chen, Yongjuan; Cosman, Peter H; Dunstan, Colin R

    2016-09-01

    The most common methods for attaching a device to the internal tissues of the human body are via sutures, clips or staples. These attachment techniques require penetration and manipulation of the tissue. Tears and leaks can often be a complication post-attachment, and scarring usually occurs around the attachment sites. To resolve these issues, it is proposed to develop a soft tissue scaffold impregnated with Rose Bengal/Chitosan solution (RBC-scaffold, 0.01% w/v Rose Bengal, 1.7% w/v Medium Molecular Weight Chitosan). This scaffold will initially attach to the tissue via a light activation method. The light activates the dye in the scaffold which causes cross-links to form between the scaffold and tissue, thus adhering them together. This is done without mechanically manipulating the surrounding tissue, thus avoiding the issues associated with current techniques. Eventually, the scaffold will be resorbed and tissue will integrate for long-term attachment. A variety of tests were performed to characterise the RBC-scaffold. Porosity, interconnectivity, and mechanical strength were measured. Light activation was performed with a broad spectrum (380-780nm) 10W LED lamp exposed to various time lengths (2-15min, Fluence range 0.4-3J/cm(2) ). Adhesive strength of the light-activated bond was measured with lap-shear tests performed on porcine stomach tissue. Cell culture viability was also assessed to confirm tissue integration potential. These properties were compared to Variotis™, an aliphatic polyester soft tissue scaffold which has proven to be viable for soft tissue regeneration. The RBC-scaffolds were found to have high porosity (86.46±2.95%) and connectivity, showing rapid fluid movement. The elastic modulus of the RBC-scaffolds (3.55±1.28MPa) was found to be significantly higher than the controls (0.15±0.058MPa, plight activation, this is comparable to the adhesion strength of fibrin glue on scaffolds. Cell attachment was seen to be similar to the controls

  8. Characterisation of a novel light activated adhesive scaffold: Potential for device attachment.

    Science.gov (United States)

    Ark, Morris; Boughton, Philip; Lauto, Antonio; Tran, Giang T; Chen, Yongjuan; Cosman, Peter H; Dunstan, Colin R

    2016-09-01

    The most common methods for attaching a device to the internal tissues of the human body are via sutures, clips or staples. These attachment techniques require penetration and manipulation of the tissue. Tears and leaks can often be a complication post-attachment, and scarring usually occurs around the attachment sites. To resolve these issues, it is proposed to develop a soft tissue scaffold impregnated with Rose Bengal/Chitosan solution (RBC-scaffold, 0.01% w/v Rose Bengal, 1.7% w/v Medium Molecular Weight Chitosan). This scaffold will initially attach to the tissue via a light activation method. The light activates the dye in the scaffold which causes cross-links to form between the scaffold and tissue, thus adhering them together. This is done without mechanically manipulating the surrounding tissue, thus avoiding the issues associated with current techniques. Eventually, the scaffold will be resorbed and tissue will integrate for long-term attachment. A variety of tests were performed to characterise the RBC-scaffold. Porosity, interconnectivity, and mechanical strength were measured. Light activation was performed with a broad spectrum (380-780nm) 10W LED lamp exposed to various time lengths (2-15min, Fluence range 0.4-3J/cm(2) ). Adhesive strength of the light-activated bond was measured with lap-shear tests performed on porcine stomach tissue. Cell culture viability was also assessed to confirm tissue integration potential. These properties were compared to Variotis™, an aliphatic polyester soft tissue scaffold which has proven to be viable for soft tissue regeneration. The RBC-scaffolds were found to have high porosity (86.46±2.95%) and connectivity, showing rapid fluid movement. The elastic modulus of the RBC-scaffolds (3.55±1.28MPa) was found to be significantly higher than the controls (0.15±0.058MPa, p<0.01) and approached reported values for human gastrointestinal tissue (2.3MPa). The maximum adhesion strength achieved of the RBC-scaffolds was 8

  9. Antigen antibody interactions

    CERN Document Server

    DeLisi, Charles

    1976-01-01

    1. 1 Organization of the Immune System One of the most important survival mechanisms of vertebrates is their ability to recognize and respond to the onslaught of pathogenic microbes to which they are conti- ously exposed. The collection of host cells and molecules involved in this recognition­ 12 response function constitutes its immune system. In man, it comprises about 10 cells 20 (lymphocytes) and 10 molecules (immunoglobulins). Its ontogenic development is c- strained by the requirement that it be capable of responding to an almost limitless variety of molecular configurations on foreign substances, while simultaneously remaining inert to those on self components. It has thus evolved to discriminate, with exquisite precision, between molecular patterns. The foreign substances which induce a response, called antigens, are typically large molecules such as proteins and polysaccharides. The portions of these with which immunoglobulins interact are called epitopes or determinants. A typical protein epitope m...

  10. HIV Molecular Immunology 2015

    Energy Technology Data Exchange (ETDEWEB)

    Yusim, Karina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Korber, Bette Tina [Los Alamos National Lab. (LANL), Los Alamos, NM (United States). Theoretical Division; Brander, Christian [Institucio Catalana de Recerca i Estudis Avancats (ICREA), Barcelona (Spain); Barouch, Dan [Beth Israel Deaconess Medical Center, Boston, MA (United States). Division of Vaccine Research; de Boer, Rob [Utrecht University, Utrecht (Netherlands). Faculty of Biology; Haynes, Barton F. [Duke Univ., Durham, NC (United States). Duke Human Vaccine Institute and Departments of Medicine, Surgery and Immunology; Koup, Richard [National Inst. of Health (NIH), Bethesda, MD (United States). Vaccine Research Center; Moore, John P. [Cornell Univ., Ithaca, NY (United States). Weill Medical College; Walker, Bruce D. [Ragon Institute, Cambridge, MA (United States); Watkins, David [Wisconsin Regional Primate Research Center, Madison, WI (United States)

    2016-04-05

    The scope and purpose of the HIV molecular immunology database: HIV Molecular Immunology is a companion volume to HIV Sequence Compendium. This publication, the 2015 edition, is the PDF version of the web-based HIV Immunology Database (http://www.hiv.lanl.gov/ content/immunology/). The web interface for this relational database has many search options, as well as interactive tools to help immunologists design reagents and interpret their results. In the HIV Immunology Database, HIV-specific B-cell and T-cell responses are summarized and annotated. Immunological responses are divided into three parts, CTL, T helper, and antibody. Within these parts, defined epitopes are organized by protein and binding sites within each protein, moving from left to right through the coding regions spanning the HIV genome. We include human responses to natural HIV infections, as well as vaccine studies in a range of animal models and human trials. Responses that are not specifically defined, such as responses to whole proteins or monoclonal antibody responses to discontinuous epitopes, are summarized at the end of each protein section. Studies describing general HIV responses to the virus, but not to any specific protein, are included at the end of each part. The annotation includes information such as cross-reactivity, escape mutations, antibody sequence, TCR usage, functional domains that overlap with an epitope, immune response associations with rates of progression and therapy, and how specific epitopes were experimentally defined. Basic information such as HLA specificities for T-cell epitopes, isotypes of monoclonal antibodies, and epitope sequences are included whenever possible. All studies that we can find that incorporate the use of a specific monoclonal antibody are included in the entry for that antibody. A single T-cell epitope can have multiple entries, generally one entry per study. Finally, maps of all defined linear epitopes relative to the HXB2 reference proteins

  11. Attachment and continuing bonds in bereavement

    Directory of Open Access Journals (Sweden)

    Anja Simonič

    2006-03-01

    Full Text Available The subject of this paper is the attachment in a relationship being one of the factors which co-form the grieving process after conjugal loss. In this integrative study about the grieving process after the loss of a partner due to sudden or expected death one or two years after the loss, the author determined that the relationship between partners represents an important indicator of the grieving process. Due to the sensitive nature of the process, the method used was a case study (seven participants were interviewed and a circular research process. The functioning of grieving persons in different areas of life was assessed with a semi-structured interview, specifically designed for this research, and with an adapted version of the Attachment Test, a part of Picture Test of Separation and Individuation (Žvelc and Žvelc, 2000. It was ascertained that particular contents in the grieving process are specifically connected with the type of relationship prior to death (ambivalent and closely connected/dependent relationship and the experiencing of the present position in relation to the deceased partner. Due to the fact that knowledge about possible maintenance/continuance of the bond between the partners has only recently become the locus of empirical research, the present study could not yet fully evaluate what kind of experience of current relationship position towards the partner contributes to healthy separation and individuation processes, i.e. grieving. Although the findings are limited to the specific context of each individual participant, the case study ascertained certain patterns in the relation between the grieving process and the attachment between partners, which indicates that there is a possibility of these in the wider population.

  12. Phenotypes of Non-Attached Pseudomonas aeruginosa Aggregates Resemble Surface Attached Biofilm

    DEFF Research Database (Denmark)

    Alhede, Morten; Kragh, Kasper Nørskov; Qvortrup, Klaus;

    2011-01-01

    of age, both aggregates and flow-cell biofilm had the same slow growth rate as a stationary phase shaking cultures. Internal structures of the aggregates matrix components and their capacity to survive otherwise lethal treatments with antibiotics (referred to as tolerance) and resistance to phagocytes......, RT-PCR as well as traditional culturing techniques to study the properties of Pseudomonas aeruginosa aggregates. We found that non-attached aggregates from stationary-phase cultures have comparable growth rates to surface attached biofilms. The growth rate estimations indicated that, independently...... were also found to be strikingly similar to flow-cell biofilms. Our data indicate that the tolerance of both biofilms and non-attached aggregates towards antibiotics is reversible by physical disruption. We provide evidence that the antibiotic tolerance is likely to be dependent on both...

  13. The Relation of Insecure Attachment States of Mind and Romantic Attachment Styles to Adolescent Aggression in Romantic Relationships

    OpenAIRE

    Miga, Erin M.; Hare, Amanda; Allen, Joseph P.; Manning, Nell

    2010-01-01

    The relation of attachment states of mind and self reported attachment relationship styles to romantic partner aggression was examined in a community sample of 93 adolescents. Higher levels of insecure-preoccupied and insecure-dismissing states of mind, as assessed by the Adolescent Attachment Interview at age 14, were predictive, respectively, of perpetration and victimization of psychological aggression in romantic relationships four years later. Partners’ romantic attachment anxiety was li...

  14. From detached to attached buildup complexes

    DEFF Research Database (Denmark)

    Rafaelsen, B.; Elvebakk, G.; Andreassen, K.;

    2008-01-01

    deposition and buildup growth bridged the detached platform with the attached platform. In the Bjarmeland Group (Lower Permian) 0.35-4.8 km wide, 1.5-27 km long and 60-420 m thick cool-water bryozoan-dominated straight, sinuous and continuous carbonate ridges or atoll-like ridges are located on top......Carbonate buildups were abundant during the Palaeozoic. Three-dimensional seismic data from the Finnmark Platform, Barents Sea, has been used to reconstruct the evolution of laterally extensive carbonate buildup complexes in space and time. The results suggest that the location of Upper Palaeozoic...

  15. Shuttle-Attached Manipulator System requirements.

    Science.gov (United States)

    Bodey, C. E.; Cepollina, F. J.

    1973-01-01

    Shuttle mission requirements and cost objectives have led to the selection of a Shuttle-Attached Manipulator System (SAMS) as a general purpose mechanism for docking, payload handling, and the general launch and retrieval of free-flying satellites. SAMS design requirements are discussed, giving attention to end effectors, kinematics, timelines, dynamics, load ratings, TV cameras and lights. Requirements for low-cost payload satellites are considered, taking into account satellites with modular subsystems which are designed for replacement and for resupply in orbit by SAMS.

  16. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm.

    Directory of Open Access Journals (Sweden)

    Morten Alhede

    Full Text Available For a chronic infection to be established, bacteria must be able to cope with hostile conditions such as low iron levels, oxidative stress, and clearance by the host defense, as well as antibiotic treatment. It is generally accepted that biofilm formation facilitates tolerance to these adverse conditions. However, microscopic investigations of samples isolated from sites of chronic infections seem to suggest that some bacteria do not need to be attached to surfaces in order to establish chronic infections. In this study we employed scanning electron microscopy, confocal laser scanning microscopy, RT-PCR as well as traditional culturing techniques to study the properties of Pseudomonas aeruginosa aggregates. We found that non-attached aggregates from stationary-phase cultures have comparable growth rates to surface attached biofilms. The growth rate estimations indicated that, independently of age, both aggregates and flow-cell biofilm had the same slow growth rate as a stationary phase shaking cultures. Internal structures of the aggregates matrix components and their capacity to survive otherwise lethal treatments with antibiotics (referred to as tolerance and resistance to phagocytes were also found to be strikingly similar to flow-cell biofilms. Our data indicate that the tolerance of both biofilms and non-attached aggregates towards antibiotics is reversible by physical disruption. We provide evidence that the antibiotic tolerance is likely to be dependent on both the physiological states of the aggregates and particular matrix components. Bacterial surface-attachment and subsequent biofilm formation are considered hallmarks of the capacity of microbes to cause persistent infections. We have observed non-attached aggregates in the lungs of cystic fibrosis patients; otitis media; soft tissue fillers and non-healing wounds, and we propose that aggregated cells exhibit enhanced survival in the hostile host environment, compared with non

  17. Mothers of Securely Attached Children with Autism Spectrum Disorder Are More Sensitive than Mothers of Insecurely Attached Children

    Science.gov (United States)

    Koren-Karie, Nina; Oppenheim, David; Dolev, Smadar; Yirmiya, Nurit

    2009-01-01

    In the current study we examined the links between maternal sensitivity and children's secure attachment in a sample of 45 preschool-age boys with Autism Spectrum Disorders (ASD). We hypothesized that mothers of securely attached children would be more sensitive to their children than mothers of insecurely attached children. Children's attachment…

  18. Attachment and God Representations among Lay Catholics, Priests, and Religious: A Matched Comparison Study Based on the Adult Attachment Interview

    Science.gov (United States)

    Cassibba, Rosalinda; Granqvist, Pehr; Costantini, Alessandro; Gatto, Sergio

    2008-01-01

    Based on the idea that believers' perceived relationships with God develop from their attachment-related experiences with primary caregivers, the authors explored the quality of such experiences and their representations among individuals who differed in likelihood of experiencing a principal attachment to God. Using the Adult Attachment Interview…

  19. Antiparasitic antibodies occur with similar frequency in patients with clinically established multiple sclerosis with or without oligoclonal bands in the cerebrospinal fluid

    Directory of Open Access Journals (Sweden)

    Fabiana Cruz Gomes da Fonseca-Papavero

    2013-08-01

    Full Text Available The "hygiene hypothesis" postulates an inverse relationship between the prevalence of parasitic infections and the frequency of multiple sclerosis (MS. Objective: It was to study whether antibodies against parasites could be demonstrated more frequently in blood serum from MS patients with oligoclonal bands (OCB than from MS patients without OCB. Methods: We studied serum samples from 164 patients who had previously been analyzed to investigate OCB. Parasitic antibodies were studied through unidimensional electrophoresis of proteins on polyacrylamide gel against Taenia antigens, searching for antiparasitic specific low molecular weight antibodies and also for antiparasitic nonspecific high molecular weight antibodies. Results: Two of the 103 patients with no evidence of OCB had antibodies of low molecular weight and 59 of them had antibodies of high molecular weight. Of the 61 patients with evidence of OCB, one showed antibodies of low molecular weight and 16 showed antibodies of high molecular weight. Conclusion: Antiparasitic antibodies are detected with similar frequency in MS patients with OCB and in MS patients without OCB.

  20. Attachment and prejudice: The mediating role of empathy.

    Science.gov (United States)

    Boag, Elle M; Carnelley, Katherine B

    2016-06-01

    In two studies, we examined the novel hypothesis that empathy is a mechanism through which the relationship between attachment patterns and prejudice can be explained. Study 1 examined primed attachment security (vs. neutral prime), empathy, and prejudice towards immigrants. Study 2 examined primed attachment patterns (secure, avoidant, anxious), empathy subscales (perspective taking, empathic concern, personal distress), and prejudice towards Muslims. Across both studies, empathy mediated the relationship between primed attachment security and low prejudice levels. The findings suggest that enhancing felt security and empathic skills in individuals high in attachment-avoidance may lead to reduced prejudice.

  1. Attachment of killed Mycoplasma gallisepticum cells and membranes to erythrocytes

    International Nuclear Information System (INIS)

    To correlate viability with attachment capacity, Mycoplasma gallisepticum cells harvested at different growth phases and treated by various agents were tested for their capacity to attach to human erythrocytes. The results show that viability per se is not essential for M. gallisepticum attachment to erythrocytes, as cells killed by ultraviolet irradiation and membranes isolated by lysing M. gallisepticum cells by various means retained attachment capacity. However, treatment of the mycoplasmas by protein-denaturing agents, such as heart, glutaraldehyde, or prolonged exposure to low pH, drastically affected or even abolished attachment, supporting the protein nature of the mycoplasma membrane components responsible for specific binding to the sialoglycoprotein receptors on the erythrocytes

  2. Modulation of the virus-receptor interaction by mutations in the V5 loop of feline immunodeficiency virus (FIV following in vivo escape from neutralising antibody

    Directory of Open Access Journals (Sweden)

    Samman Ayman

    2010-04-01

    Full Text Available Abstract Background In the acute phase of infection with feline immunodeficiency virus (FIV, the virus targets activated CD4+ T cells by utilising CD134 (OX40 as a primary attachment receptor and CXCR4 as a co-receptor. The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" determinant on CD134 formed by cysteine-rich domains (CRDs 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection. These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists. In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo. Results Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134. Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134. Conclusions The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes to the virus-receptor interaction. Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.

  3. Binding of a neutralizing antibody to dengue virus alters the arrangement of surface glycoproteins

    Energy Technology Data Exchange (ETDEWEB)

    Lok, Shee-Mei; Kostyuchenko, Victor; Nybakken, Grant E.; Holdaway, Heather A.; Battisti, Anthony J.; Sukupolvi-Petty, Soila; Sedlak, Dagmar; Fremont, Daved H.; Chipman, Paul R.; Roehrig, John T.; Diamond, Michael S.; Kuhn, Richard J.; Rossmann, Michael G. (Purdue); (WU-MED); (CDC)

    2008-04-02

    The monoclonal antibody 1A1D-2 has been shown to strongly neutralize dengue virus serotypes 1, 2 and 3, primarily by inhibiting attachment to host cells. A crystal structure of its antigen binding fragment (Fab) complexed with domain III of the viral envelope glycoprotein, E, showed that the epitope would be partially occluded in the known structure of the mature dengue virus. Nevertheless, antibody could bind to the virus at 37 degrees C, suggesting that the virus is in dynamic motion making hidden epitopes briefly available. A cryo-electron microscope image reconstruction of the virus:Fab complex showed large changes in the organization of the E protein that exposed the epitopes on two of the three E molecules in each of the 60 icosahedral asymmetric units of the virus. The changes in the structure of the viral surface are presumably responsible for inhibiting attachment to cells.

  4. Charisma and attachment theory: a crossdisciplinary interpretation.

    Science.gov (United States)

    Aberbach, D

    1995-08-01

    The attachment theory of Bowlby and his followers has not previously been applied to the interpretation of charismatic phenomena in the bonding of large numbers of people with their leaders in crisis. This essay, which builds on the author's 'Surviving trauma: loss, literature and psychoanalysis', attempts to use attachment theory and sociological concepts such as homogamy, anomie, negative imprinting and de-individuation, as well as classical Freudian concepts such as transference and splitting of the ego, in interpreting the charismatic bond. It is argued that charismatic homogamy becomes viable at the point of intersection between the inner world of the charismatic leader and social and political reality. The bonding of the individual and the public may be based partly upon a symbolic link between public crisis and the charismatic's experience of trauma that has deeply scarred or even ended the affectional bonds in his family of orientation. This trauma, however, is a source of insight and power as well as of disability, for it has schooled him in crisis and given him the capacity to offer directional leadership. The charismatic and his society are bonded in crisis through a mutual attempt to break free of anomie and alienation, and a sense of powerlessness and despair. PMID:8543437

  5. Predicting Envelope Leakage in Attached Dwellings

    Energy Technology Data Exchange (ETDEWEB)

    Faakye, O. [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States); Arena, L. [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States); Griffiths, D. [Consortium for Advanced Residential Buildings (CARB), Norwalk, CT (United States)

    2013-07-01

    The most common method for measuring air leakage is to use a single blower door to pressurize and/or depressurize the test unit. In detached housing, the test unit is the entire home and the single blower door measures air leakage to the outside. In attached housing, this 'single unit', 'total', or 'solo' test method measures both the air leakage between adjacent units through common surfaces as well air leakage to the outside. Measuring and minimizing this total leakage is recommended to avoid indoor air quality issues between units, reduce energy losses to the outside, reduce pressure differentials between units, and control stack effect. However, two significant limitations of the total leakage measurement in attached housing are: for retrofit work, if total leakage is assumed to be all to the outside, the energy benefits of air sealing can be significantly over predicted; for new construction, the total leakage values may result in failing to meet an energy-based house tightness program criterion. The scope of this research is to investigate an approach for developing a viable simplified algorithm that can be used by contractors to assess energy efficiency program qualification and/or compliance based upon solo test results.

  6. Jet-diffuser Ejector - Attached Nozzle Design

    Science.gov (United States)

    Alperin, M.; Wu, J. J.

    1980-01-01

    Attached primary nozzles were developed to replace the detached nozzles of jet-diffuser ejectors. Slotted primary nozzles located at the inlet lip and injecting fluid normal to the thrust axis, and rotating the fluid into the thrust direction using the Coanda Effect were investigated. Experiments indicated excessive skin friction or momentum cancellation due to impingement of opposing jets resulted in performance degradation. This indicated a desirability for location and orientation of the injection point at positions removed from the immediate vicinity of the inlet surface, and at an acute angle with respect to the thrust axis. Various nozzle designs were tested over a range of positions and orientations. The problems of aircraft integration of the ejector, and internal and external nozzle losses were also considered and a geometry for the attached nozzles was selected. The effect of leaks, protrusions, and asymmetries in the ejector surfaces was examined. The results indicated a relative insensitivity to all surface irregularities, except for large protrusions at the throat of the ejector.

  7. [Early attachement relationships and epigenetic customization].

    Science.gov (United States)

    Rocchi, Giordana; Serio, Valentina; Carluccio, Giuseppe Mattia; Marini, Isabella; Meuti, Valentina; Zaccagni, Michela; Giacchetti, Nicoletta; Aceti, Franca

    2015-01-01

    Recently, new findings in epigenetic science switched the focus from the observation of physiological intragenomic dynamics to the idea of an environmental co-construction of phenotypic expression. In psichodynamic field, objectual relations and attachement theoreticians emphasized the interpersonal dimension of individual development, focusing the attention on the relational matrix of self organization. The construction of stable affective-behavioral traits throughout different parenting styles has actually found a coincidence in ethological studies, which have explored the epigenetic processes underlying the relationship between caregiving and HPA stress responsiveness. An adequate parenting style seems to support affective regulation throughout psychobiological hidden moderators, which would tend to rebalance the physiological systems homeostasis; an unconfident attachment style would promote, on the other hand, the allostatic load rise. Sites of longlife epigenetic susceptibility have also been identified in humans; although associated with risk of maladaptive developing in adverse environmental conditions, they seem to confer protection under favorable conditions. This persisting possibility of reorganization of stable traits throughout lifetime, which seems to be activated by a relevant environmental input, grant to significant relationships, and to therapeutical one as well, an implicit reconditioning potential which could result into the configuration of new stable affective-behavioral styles.

  8. Charisma and attachment theory: a crossdisciplinary interpretation.

    Science.gov (United States)

    Aberbach, D

    1995-08-01

    The attachment theory of Bowlby and his followers has not previously been applied to the interpretation of charismatic phenomena in the bonding of large numbers of people with their leaders in crisis. This essay, which builds on the author's 'Surviving trauma: loss, literature and psychoanalysis', attempts to use attachment theory and sociological concepts such as homogamy, anomie, negative imprinting and de-individuation, as well as classical Freudian concepts such as transference and splitting of the ego, in interpreting the charismatic bond. It is argued that charismatic homogamy becomes viable at the point of intersection between the inner world of the charismatic leader and social and political reality. The bonding of the individual and the public may be based partly upon a symbolic link between public crisis and the charismatic's experience of trauma that has deeply scarred or even ended the affectional bonds in his family of orientation. This trauma, however, is a source of insight and power as well as of disability, for it has schooled him in crisis and given him the capacity to offer directional leadership. The charismatic and his society are bonded in crisis through a mutual attempt to break free of anomie and alienation, and a sense of powerlessness and despair.

  9. A longitudinal study of maternal attachment and infant developmental outcomes.

    Science.gov (United States)

    Alhusen, Jeanne L; Hayat, Matthew J; Gross, Deborah

    2013-12-01

    Extant research has demonstrated that compared to adults with insecure attachment styles, more securely attached parents tend to be more responsive, sensitive, and involved parents, resulting in improved outcomes for their children. Less studied is the influence of a mother's attachment style on her attachment to her unborn child during pregnancy and the consequent developmental outcomes of the child during early childhood. Thus, the aim of this prospective longitudinal study was to examine the relationship between maternal-fetal attachment (MFA) during pregnancy and infant and toddler outcomes and the role of mothers' attachment style on early childhood developmental outcomes in an economically disadvantaged sample of women and their children. Gamma regression modeling demonstrated that an avoidant maternal attachment style (b = .98, 95 % CI [.97, .98], p styles and greater depressive symptomatology were more likely to have children demonstrating early childhood developmental delays than those women with less avoidant attachment styles and less depressive symptomatology. Furthermore, women reporting higher MFA during pregnancy had more secure attachment styles, and their children had more optimal early childhood development than those women reporting lower MFA and less secure attachment styles. Findings have implications for enhancing early intervention programs aimed at improving maternal and childhood outcomes. An earlier identification of disruptions in attachment may be beneficial in tailoring interventions focused on the mother-child dyad.

  10. Cutting Gordian Knots: Reducing Prejudice Through Attachment Security.

    Science.gov (United States)

    Saleem, Muniba; Prot, Sara; Cikara, Mina; Lam, Ben C P; Anderson, Craig A; Jelic, Margareta

    2015-11-01

    The positive role of secure attachment in reducing intergroup biases has been suggested in prior studies. We extend this work by testing the effects of secure attachment primes on negative emotions and aggressive behaviors toward outgroup members across four experiments. Results from Studies 1A and 1B reveal that secure attachment prime, relative to neutral, can reduce negative outgroup emotions. In addition, Studies 1B and 3 results rule out positive mood increase as an alternative explanation for the observed effects. Results from Studies 2 and 3 reveal that secure attachment primes can reduce aggressive behavior toward an outgroup member. The effect of secure attachment primes on outgroup harm was found to be fully mediated by negative emotions in Studies 2 and 3. An interaction between secure attachment primes and ingroup identification in Study 2 indicated that the positive effects of secure attachment in reducing outgroup harm may be especially beneficial for highly identified ingroup members.

  11. The association between state attachment security and state Mindfulness.

    Directory of Open Access Journals (Sweden)

    Christopher A Pepping

    Full Text Available Recent research suggests that attachment and mindfulness are related, though the nature of this association is unclear. Here we present two studies examining whether there is a causal relationship between state attachment and state mindfulness. Study 1 investigated the effects of experimentally increasing state mindfulness on state attachment security. State mindfulness was successfully enhanced, but this led to no change in state attachment security. Study 2 investigated the effects of experimentally enhancing state attachment security on state mindfulness. State attachment security was successfully enhanced, but this did not lead to any change in state mindfulness. These findings suggest that there is not a direct, immediate causal relationship between state attachment and state mindfulness as a result of brief experimental manipulations. Future research should examine these associations in longer term interventions.

  12. Relationship between deposition and attachment rates in Jacobi room model

    International Nuclear Information System (INIS)

    It is shown in this work that parameters of the Jacobi model, which describes behavior of short-lived radon progeny, are not independent. The relationship between deposition rate of attached radon progeny and attachment rate of their unattached fraction was determined in this paper. It was found that deposition rate increases when the attachment rate is smaller; this effect is more pronounced for larger friction velocity. The deposition rate of attached radon progeny is presented here as a function of friction velocity, ventilation and attachment rate. Deposition rate of attached fraction was estimated in the range 0.012-0.46 h-1, when attachment rate varies from 10 h-1 to 100 h-1.

  13. Mediators of the Link Between Adult Attachment and Mindfulness

    Directory of Open Access Journals (Sweden)

    Jon G. Caldwell

    2013-12-01

    Full Text Available The capacity to be mindfully aware of the present moment without judgment is associated with a number of positive psychological and physiological outcomes. Experiences in attachment relationships are related to specific cognitive-emotional patterns that may contribute to dispositional mindfulness. A sample of adults (N = 93 completed questionnaires regarding adult attachment, rumination, thought suppression, attentional control, and mindfulness. Attachment-related avoidance predicted lower levels of mindfulness, a relation mediated by thought suppression and poorer attentional control. Attachment-related anxiety also predicted lower levels of mindfulness, a relation mediated by rumination and poorer attentional control. The results suggest that in the context of insecure attachment relationships thought suppression and rumination defend against personal and interpersonal losses by deactivating (in the case of avoidance or hyperactivating (in the case of anxiety the attachment system. These habitual defensive patterns may be important links between adult attachment orientations and mindfulness.

  14. Relationships between attachment and marital satisfaction in married couples

    Directory of Open Access Journals (Sweden)

    Patrícia Gallerová

    2016-01-01

    Full Text Available Theory of attachment strongly influences exploring of close relationships in childhood and in adulthood as well. According Bowlby attachment is "lasting relationship bond characterized by need of seeking and maintaining proximity with a person in stressful situations especially (Bowbly, 2010. Hazan a Shaver (1987 applied theory of early attachment in romantic relationships of adults. Behavior of adult human in relationships is more or less predictable by style of attachment in childhood (Feeney, 1999. Brennan, Clark a Shaver (1998 created four-dimensional model of attachment which was based on Ainsworth´s theory as well. The model was formed of two dimensions - anxiety and avoidance. The authors identified four types of attachment: secure, fearful, dismissive and preoccupied style of attachment (Brennan, Clark, & Shaver, 1998. Satisfaction in romantic relationship can be explained as a degree in which is relationship for a human enojyable. Attachment influences satisfaction in relationship in terms of meeting need of proximity and safety (Mikulincer, Florian, Cowan, & Cowan, 2002. Several researches show that safe attachment is associated with higher satisfaction in marriage and on the other hand people with insecure style of attachment show lower degree of satisfaction in relationship (Alexandrov, Cowan, & Cowan, 2005; Treboux, Crowell, & Waters, 2004. At the same time style of attachment of the partner also influences individual a lot, satisfaction does not depend only on his own style of attachment but also on attachment of his partner (Farinelli, & McEwan, 2009. The study examined relations between the relationship attachment and marital satisfaction. The goal was to explain the relationship between the adult attachment and marital satisfaction of the individual and her/his husband/wife. The research examined relationship between adult attachment and marital satisfaction as well. Quantitative questionnaire survey: The battery consisted of

  15. Anxious attachment and psychological distress in cardiac rehabilitation patients.

    Science.gov (United States)

    West, M; Sarah Rose, M; Brewis, C S

    1995-06-01

    This study investigated the relevance of anxious attachment to the differentiation of psychologically distressed and non-psychologically distressed cardiac patients. Attachment is a biologically based behavioral system in which proximity to a special other is sought or maintained to achieve a sense of safety and security. Anxious attachment, as the name denotes, fails to achieve the function of attachment in the sense of individuals having little or no confidence in the availability of their attachment figures. Empirically, three scales (feared loss of the attachment figure, proximity seeking and separation protest) capture the features of anxious attachment as elaborated by Bowlby. These scales were administered to 178 cardiac rehabilitation patients drawn from the cardiac rehabilitation program of the Calgary General Hospital. The results indicate that feared loss and proximity seeking differentiated psychologically distressed from non-psychologically distressed patients. The implications of this finding for the understanding of psychologically distressed cardiac patients are discussed.

  16. The Use of Monoclonal Antibodies in Human Prion Disease

    Science.gov (United States)

    Bodemer, Walter

    Detection of PrP and its pathological isoform(s) is the key to understanding the etiology and pathogenesis of transmissible spongiform encephalopathy. There is ample evidence that PrP isoforms constitute a major component of an unknown and perhaps unconventional infectious agent. An etiological relationship between human and zoonotic transmissible spongiform encephalopathies may be revealed with monoclonal antibodies. Knowledge of the conformational transition rendering a nonpathogenic, almost ubiquitous cellular protein into a pathogenic one is crucial to defining pathomechanisms. The stepwise or even continuous formation of pathogenic molecules can be monitored. Any improvement in the early diagnosis could help to conceive new therapeutic measures which are not currently available. Determination of PrP isoforms in tissue, cells, or body fluids may be of prognostic value. Many experimental approaches in molecular medicine and molecular biology of the prion protein already rely on monoclonal antibodies. Recombinant antibodies such as the single-chain Fv may soon replace traditional hybridoma techniques. Binding affinity can easily be manipulated by a number of techniques, including in vitro mutagenesis - a step which could never be carried out using the traditional hybridoma technology. Monoclonal antibodies are and will remain an essential support for ongoing research on the prion protein in general and on the unconventional infectious prions.

  17. Preparation and characterization of polyclonal antibodies against ARL-1 protein

    Institute of Scientific and Technical Information of China (English)

    Jun-Fei Jin; Liu-Di Yuan; Li Liu; Zhu-Jiang Zhao; Wei Xie

    2003-01-01

    AIM: To prepare and characterize polyclonal antibodies against aldose reductase-like (ARL-1) protein.METHODS: ARL-L gene was inserted into the E.coli expression vector pGEX-4T-1(His)6C and vector pQE-30. Recombinant ARL1 proteins named ARL-(His)6 and ARL-GST were expressed.They were purified by affinity chromatography. Sera from domestic rabbits immunized with ARL-(His)6 were purified by CNBr-activated sepharose 4B coupled ARL-GST. Polyclonal antibodies were detected by Western blotting.RESULTS: Recombinant proteins of ARL-(His)6 with molecular weight of 35.7 KD and ARL-GST with molecular weight of 60.8 KD were highly expressed. The expression levels of ARL-GST and ARL-(His)6 were 15.1% and 27.7 %among total bacteria proteins, respectively. They were soluble, predominantly in supernatant. After purification by non-denatured way, SDS-PAGE showed one band. In the course of polyclonal antibodies purification, only one elution peak could be seen. Western blotting showed positive signals in the two purified proteins and the bacteria transformed with pGEX-4T-1(His)6 C-ARL and pQE-30-ARL individually.CONCLUSION: Polyclonal antibodies are purified and highly specific against ARL-1 protein. ARL-GST and ARL-(His)6 are highly expressed and purified.

  18. Elevated levels of measles antibodies in children with autism.

    Science.gov (United States)

    Singh, Vijendra K; Jensen, Ryan L

    2003-04-01

    Virus-induced autoimmunity may play a causal role in autism. To examine the etiologic link of viruses in this brain disorder, we conducted a serologic study of measles virus, mumps virus, and rubella virus. Viral antibodies were measured by enzyme-linked immunosorbent assay in the serum of autistic children, normal children, and siblings of autistic children. The level of measles antibody, but not mumps or rubella antibodies, was significantly higher in autistic children as compared with normal children (P = 0.003) or siblings of autistic children (P vaccine virus revealed that the antibody was directed against a protein of approximately 74 kd molecular weight. The antibody to this antigen was found in 83% of autistic children but not in normal children or siblings of autistic children. Thus autistic children have a hyperimmune response to measles virus, which in the absence of a wild type of measles infection might be a sign of an abnormal immune reaction to the vaccine strain or virus reactivation.

  19. The antineutrophil antibody in uveitis.

    OpenAIRE

    Young, D W

    1991-01-01

    Ninety eight patients with uveitis of various types were tested for the presence of the antineutrophil antibody or ANCA by an indirect immunofluorescence method. This antibody is found in patients with diseases associated with small vessel vasculitis, including Wegener's granulomatosis and microscopic polyarteritis. Eleven true positive cases were found. A positive test was not associated with the anatomical site of the uveitis but was related to the time course of the disease. In particular ...

  20. Functional effects of anticardiolipin antibodies.

    Science.gov (United States)

    Harris, E N; Pierangeli, S S

    1996-10-01

    The 'lupus anticoagulant' phenomenon is the best documented functional effect of antiphospholipid (aPL) antibodies, occurring either by inhibition of the prothrombinase and/or Factor X activation reactions. Understanding the mechanism by which aPL antibodies inhibit phospholipid dependent coagulation reactions may yield important clues about their 'thrombogenic effects' in vivo. We conducted a series of studies to determine the specificity, diversity, and mechanism by which aPL antibodies inhibit phospholipid dependent reactions. Results showed that purified immunoglobulins with lupus anticoagulant and anti-cardiolipin activities were absorbed by negatively charged phospholipids and both activities were recovered from the phospholipid-antibody precipitate. Purified aPL antibodies inhibited the prothrombinase reaction in a plasma free system in which beta 2-glycoprotein 1 (beta 2-GP1) was absent. Affinity purified aPL antibodies had 25-50 times the inhibitory activity of immunoglobulin preparations. The phospholipid binding proteins, beta 2-GPI and placental anticoagulant protein I (PAP I), independently inhibited the prothrombinase reaction, and when these proteins were combined with aPL, inhibition of the prothrombinase reaction was additive. Antibodies of syphilis had no inhibitory effect, partially accounted for by lack of specificity for phosphotidylserine (PS). Although aPL antibodies inhibited the protein C activation reaction, there was no correlation of these activities with inhibition of the prothrombinase reaction. Together, these results show that aPL exert their effects by interaction with negatively charged phospholipids, in particular phosphotidylserine, but lack of correlation between inhibition of the prothrombinase and protein C activation reactions, suggests that the nature of the coagulation protein is also important. PMID:8902763