scholarly journals Enzymic and immunochemical properties of lysozyme. Accurate definition of the antigenic site around the disulphide bridge 30-115 (site 3) by ‘surface simulation’ synthesis

1977 ◽  
Vol 167 (3) ◽  
pp. 571-581 ◽  
Author(s):  
Ching-Li Lee ◽  
M. Zouhair Atassi
Keyword(s):  
Antigenic Site ◽  
Surface Region ◽  
Synthetic Approach ◽  
Disulphide Bridge ◽  
Peptide Bonds ◽  
Preferred Direction ◽  
Accurate Definition ◽  
Definition Of ◽  
A Site ◽  
Antigenic Reactivity

1. Previous reports from this laboratory have shown that both Lys-33 and Lys-116 are parts of an antigenic site in native lysozyme. Similar studies of tyrosine derivatives indicated that one or both of Tyr-20 and Tyr-23 are located in or very close to an antigenic site in lysozyme. The site, which was located around the disulphide bridge 30–115, was recently shown unequivocally to include the residues Tyr-20, Arg-21, Lys-116, Asn-113, Arg-114, Phe-34 and Lys-33. This was confirmed by the ‘surface-simulation’ synthetic approach that we have recently developed, in which the foregoing eight surface residues were directly linked via peptide bonds, with intervening spacers where appropriate, into a single peptide. The peptide does not exist in native lysozyme, but simulates a surface region of it. 2. In the present work several surface-simulation peptides were synthesized representing various parts of the region, to determine the minimum structural feature that retains full antigenic reactivity and to investigate if the spatially constructed antigenic site has a preferred direction. 3. The peptide Lys-Asn-Arg-Gly-Phe-Lys exhibited a remarkable inhibitory activity towards the immune reaction of lysozyme and accounted entirely for the maximum expected reactivity of the site in the native protein (i.e. about one-third of the total lysozyme reactivity). An immunoadsorbent of the peptide bound about one-third of the total antibody to lysozyme. 4. The residues Tyr-20 and Arg-21 are not part of the site. The previously reported immunochemical effect observed on nitration of Tyr-20 was due to a deleterious ionic effect exerted by the modified tyrosine residue on the adjacent Lys-96, which is in an entirely different antigenic site of lysozyme. Thus the modification of Tyr-20 impairs the reactivity of an adjacent antigenic site, even though the residue itself is not part of a site. The conformational and immunochemical implications of this finding are discussed. 5. The antigenic site therefore comprises the five spatially adjacent residues Lys-116, Asn-113, Arg-114, Phe-34, Lys-33. The antigenic site exhibited a preferred direction (Lys-116 to Lys-33), since the reverse surface-simulation synthetic sequence was immunochemically inefficient. The site describes a line which circumscribes part [2.1nm in C(α)–C(α) distance from Lys-116 to Lys-33] of the surface of the molecule.

scholarly journals Delineation of the third antigenic site of lysozyme by application of a novel ‘surface-simulation’ synthetic approach directly linking the conformationally adjacent residues forming the site

1976 ◽  
Vol 159 (1) ◽  
pp. 89-93 ◽  
Author(s):  
C L Lee ◽  
M Z Atassi
Keyword(s):  
Chemical Reactivity ◽  
Antigenic Site ◽  
Surface Region ◽  
Synthetic Approach ◽  
The Novel ◽  
Disulphide Bridge ◽  
Native Proteins ◽  
Novel Approach ◽  
Peptide Linkage ◽  
Imaginary Line

We have previously shown that an antigenic site in native lysozyme resides around the disulphide bridge 30-115 and incorporates Lys-33 and Lys-116 and one or both of Tyr-20 and Tyr-23. These residues fall in an imaginary line circumscribing part of the surface of the molecule and passing through the spatially adjacent residues Tyr-20, Arg-21, Tyr-23, Lys-116, Asn-113, Arg-114, Phe-34 and Lys-33. The identity of the site was confirmed by demonstrating that the synthetic peptide Tyr-Arg-Tyr-Gly-Lys-Asn-Arg-Gly-Phe-Lys (which does not exist in lysozyme but simulates a surface region of it), and an analogue in which glycine replaced Tyr-23, possessed remarkable immuno-chemical reactivity that accounted entirely for the expected reactivity of the site in native lysozyme. Tyr-23 is not part of the site, and its contribution was satisfied by a glycine spacer. The novel approach presents a powerful technique for the delineation of antigenic (and other binding) sites in native proteins and confirms that these need not always comprise residues in direct peptide linkage.

scholarly journals Boundary refinement of the lysozyme antigenic site around the disulphide bond 6–127 (site 1) by ‘surface-simulation’ synthesis

1978 ◽  
Vol 171 (2) ◽  
pp. 419-427 ◽  
Author(s):  
M. Zouhair Atassi ◽  
Ching-Li Lee
Keyword(s):  
Synthetic Peptide ◽  
Antigenic Site ◽  
Surface Region ◽  
Disulphide Bond ◽  
Direct Verification ◽  
Conformational Freedom ◽  
Directional Preference ◽  
Definition Of ◽  
Antigenic Reactivity

1. We have previously shown that an antigenic site (site 1) in native lysozyme resides around the disulphide bond 6–127 and, by classical synthesis of nine disulphide peptides, the antigenic site was accurately narrowed down to the structure Cys(6)–Arg(14)–[Cys(6)–Cys(127)] –Gly(126)–Arg(128). Only a few residues on this disulphide peptide were proposed to be involved in the reactivity with antibody. However, this lacked direct verification and the role of Arg-128 remained uncertain. 2. In the present work, several peptides were designed and synthesized by the surface-simulation concept devised in our laboratory. These enabled the precise definition of the site as well as the investigation of its conformational and directional requirements. 3. The results showed that the antigenic site (site 1) is made up of the spatially contiguous surface residues: Arg-125, Arg-5, Glu-7, Arg-14, Lys-13. The surface-simulation synthetic peptide Arg-Gly-Gly-Arg-Gly-Glu-Gly-Gly-Arg-Lys (which does not exist in native lysozyme, but copies a surface region of it) accounted entirely for the maximum expected reactivity of the site (i.e. about one-third of the total antigenic reactivity of lysozyme). An immunoadsorbent of the peptide also removed about one-third of the total lysozyme antibodies. 4. The antigenic site exhibited restricted conformational freedom. The achievement of the full reactivity of the site by surface-simulation synthesis requires the appropriate choice of spacer separation between its reactive residues. The surface-simulation synthetic site exhibits the same mono-directional preference (Arg-125 to Lys-13) for the rabbit and goat antisera so far tested. The site describes a line which encircles a part (3.01 nm in C(α)-to-C(α) distance from Arg-125 to Lys-13) of the surface of the molecule.

Resolution and measurement in the scanning electron microscope

1987 ◽  
Vol 45 ◽  
pp. 534-537 ◽  
Author(s):  
Michael T. Postek
Keyword(s):  
Electron Microscope ◽  
Scanning Electron Microscope ◽  
Engineering Design ◽  
Resolving Power ◽  
Practical Applications ◽  
Instrument Resolution ◽  
Accurate Definition ◽  
Definition Of ◽  
Scanning Electron ◽  
Better Than

The term ultimate resolution or resolving power is the very best performance that can be obtained from a scanning electron microscope (SEM) given the optimum instrumental conditions and sample. However, as it relates to SEM users, the conventional definitions of this figure are ambiguous. The numbers quoted for the resolution of an instrument are not only theoretically derived, but are also verified through the direct measurement of images on micrographs. However, the samples commonly used for this purpose are specifically optimized for the measurement of instrument resolution and are most often not typical of the sample used in practical applications.SEM RESOLUTION. Some instruments resolve better than others either due to engineering design or other reasons. There is no definitively accurate definition of how to quantify instrument resolution and its measurement in the SEM.

Dasein, personeidad, intersubjetividad y persona-núcleo. El sujeto relacional después de Heidegger, en Zubiri, Apel y Polo. Dasein, Personhood, Inter-subjectivity and Nucleus-Person. The Relational Subject after Heidegger, in Zubiri, Apel and Polo

2017 ◽  
Author(s):  
Carlos Ortiz de Landázuri
Keyword(s):  
Heuristic Strategies ◽  
Accurate Definition ◽  
Being There ◽  
Definition Of

Heidegger, Zubiri, Apel y Polo habrían propuesto una definición más correcta de las respectivas nociones de sujeto relacional humano, a saber: “Dasein” o “ser-ahí”; “personeidad” o “esencia abierta”; “intersubjetividad” o “la llamada por parte de los entes a diversos interlocutores”; y, finalmente, “persona-núcleo” o “agente mediador entre los entes y el ser”. Se pretendía así evitar una vuelta a las paradojas del “sujeto transcendental” en Kant, del “yo absoluto” en Hegel o del “sujeto fenomenológico” en Husserl. Sin embargo en cada caso se siguieron estrategias heurísticas específicamente distintas a la hora de conceptualizar dicho sujeto relacional: Heidegger propuso una superación de la noción de “sujeto fenomenológico” en Husserl; Zubiri, en cambio, defendería una recuperación de la noción de “sujeto fenomenológico” en Husserl; por su parte, Apel propondría una reformulación semióticamente transformada del “Dasein” heideggeriano; finalmente, Polo propondría una reformulación gnoseológica de la noción de “Dasein” heideggeriano.Heidegger, Zubiri, Apel, and Polo have proposed a more accurate definition of the respective notions of human relational subject: “Dasein” or “being-there”; “Personhood” or “open essence”; “inter-subjectivity” or “entities’ appeal to diverse interlocutors”; and, finally, “nucleus-person” or “mediator between entities and being”. The aim is to avoid a return to Kant’s transcendental subject paradoxes and Hegel’s “absolute I” or Husserl´s “fenomenological subject”. But in each case specifically different heuristic strategies were followed when conceptualizing said relational subject: Heidegger proposed overcoming the notion of “phenomenological subject” in Husserl; Zubiri, however, defend the recovery of the notion of “phenomenological subject” in Husserl; meanwhile, Apel propose a transformed semiotically reformulation of Heidegger’s “Dasein”; finally, Polo propose a reformulation of the epistemological notion of Heidegger’s “Dasein”.

MONARCHS, TRAVELLERS AND EMPIRE IN THE PACIFIC'S AGE OF REVOLUTIONS

2020 ◽  
Vol 30 ◽  
pp. 77-96
Author(s):  
Sujit Sivasundaram
Keyword(s):  
Pacific Islanders ◽  
Modern World ◽  
Global History ◽  
The Past ◽  
The Pacific ◽  
Cultural Terms ◽  
The Pacific Ocean ◽  
Definition Of ◽  
The Uk ◽  
A Site

AbstractThe Pacific has often been invisible in global histories written in the UK. Yet it has consistently been a site for contemplating the past and the future, even among Britons cast on its shores. In this lecture, I reconsider a critical moment of globalisation and empire, the ‘age of revolutions’ at the end of the eighteenth century and the start of the nineteenth century, by journeying with European voyagers to the Pacific Ocean. The lecture will point to what this age meant for Pacific islanders, in social, political and cultural terms. It works with a definition of the Pacific's age of revolutions as a surge of indigeneity met by a counter-revolutionary imperialism. What was involved in undertaking a European voyage changed in this era, even as one important expedition was interrupted by news from revolutionary Europe. Yet more fundamentally vocabularies and practices of monarchy were consolidated by islanders across the Pacific. This was followed by the outworkings of counter-revolutionary imperialism through agreements of alliance and alleged cessation. Such an argument allows me, for instance, to place the 1806 wreck of the Port-au-Prince within the Pacific's age of revolutions. This was an English ship used to raid French and Spanish targets in the Pacific, but which was stripped of its guns, iron, gunpowder and carronades by Tongans. To chart the trajectory from revolution and islander agency on to violence and empire is to appreciate the unsettled paths that gave rise to our modern world. This view foregrounds people who inhabited and travelled through the earth's oceanic frontiers. It is a global history from a specific place in the oceanic south, on the opposite side of the planet to Europe.

scholarly journals Advancing UK Regulatory Science Strategy in the Context of Global Regulation: a Stakeholder Survey

2021 ◽  
Author(s):  
Samantha Cruz Rivera ◽  
Barbara Torlinska ◽  
Eliot Marston ◽  
Alastair K. Denniston ◽  
Kathy Oliver ◽  
...  
Keyword(s):  
Pay For Performance ◽  
Regulatory Science ◽  
International Strategy ◽  
Free Text ◽  
The European Union ◽  
Accurate Definition ◽  
Definition Of ◽  
Healthcare Innovation ◽  
The Uk ◽  
Medium Enterprises

Abstract Background The UK’s transition from the European Union creates both an urgent need and key opportunity for the UK and its global collaborators to consider new approaches to the regulation of emerging technologies, underpinned by regulatory science. This survey aimed to identify the most accurate definition of regulatory science, to define strategic areas of the regulation of healthcare innovation which can be informed through regulatory science and to explore the training and infrastructure needed to advance UK and international regulatory science. Methods A survey was distributed to UK healthcare professionals, academics, patients, health technology assessment agencies, ethicists and trade associations, as well as international regulators, pharmaceutical companies and small or medium enterprises which have expertise in regulatory science and in developing or applying regulation in healthcare. Subsequently, a descriptive quantitative analyses of survey results and directed thematic analysis of free-text comments were applied. Results Priority areas for UK regulatory science identified by 145 participants included the following: flexibility: the capability of regulations to adapt to novel products and target patient outcomes; co-development: collaboration across sectors, e.g. patients, manufacturers, regulators, and educators working together to develop appropriate training for novel product deployment; responsiveness: the preparation of frameworks which enable timely innovation required by emerging events; speed: the rate at which new products can reach the market; reimbursement: developing effective tools to track and evaluate outcomes for “pay for performance” products; and education and professional development. Conclusions The UK has a time-critical opportunity to establish its national and international strategy for regulatory science leadership by harnessing broader academic input, developing strategic cross-sector collaborations, incorporating patients’ experiences and perspectives, and investing in a skilled workforce.

DELIGHTFUL COXCOMBS TO INDUSTRIOUS MEN: FASHIONABLE POLITICS IN CECIL AND PENDENNIS

2002 ◽  
Vol 30 (1) ◽  
pp. 289-304 ◽  
Author(s):  
Claire Nicolay
Keyword(s):  
Nineteenth Century ◽  
Eighteenth Century ◽  
Middle Class ◽  
Upward Mobility ◽  
Late Nineteenth Century ◽  
Class A ◽  
Late Nineteenth ◽  
Definition Of ◽  
A Site ◽  
Trade Office

THOMAS CARLYLE’S CONTEMPTUOUS DESCRIPTION of the dandy as “a Clothes-wearing Man, a Man whose trade, office, and existence consists in the wearing of Clothes” (313) has survived as the best-known definition of dandyism, which is generally equated with the foppery of eighteenth-century beaux and late nineteenth-century aesthetes. Actually, however, George Brummell (1778–1840), the primary architect of dandyism, developed not only a style of dress, but also a mode of behavior and style of wit that opposed ostentation. Brummell insisted that he was completely self-made, and his audacious self-transformation served as an example for both parvenus and dissatisfied nobles: the bourgeois might achieve upward mobility by distinguishing himself from his peers, and the noble could bolster his faltering status while retaining illusions of exclusivity. Aristocrats like Byron, Bulwer, and Wellington might effortlessly cultivate themselves and indulge their taste for luxury, while at the same time ambitious social climbers like Brummell, Disraeli, and Dickens might employ the codes of dandyism in order to establish places for themselves in the urban world. Thus, dandyism served as a nexus for the declining aristocratic elite and the rising middle class, a site where each was transformed by the dialectic interplay of aristocratic and individualistic ideals.

Cervical cytologic abnormalities and negative colposcopy: histologic assessment

1994 ◽  
Vol 4 (5) ◽  
pp. 348-351 ◽  
Author(s):  
R. Chenoy ◽  
S. Manohar ◽  
C. W.E. Redman ◽  
D. M. Luesley
Keyword(s):  
Cervical Cytology ◽  
Histologic Diagnosis ◽  
Abnormal Cervical Cytology ◽  
Accurate Definition ◽  
Cone Biopsy ◽  
Histologic Evaluation ◽  
Simple Regression Analysis ◽  
Definition Of ◽  
Cytologic Abnormalities ◽  
Intraepithelial Lesions

Colposcopic assessment may be normal in the presence of severe or persistent minor cytologic abnormality. To assess the significance of negative satisfactory colposcopy in patients with abnormal cervical smears, a retrospective review was carried out on 1170 patients who had undergone out-patient loop diathermy excision for abnormal cervical cytology. Of these, 69 patients were treated for abnormal cervical cytology, despite normal colposcopic findings. Cytologic abnormalities ranged from persistent borderline changes to severe dyskariosis. Histologic assessment of the excision specimens revealed cervical intraepithalial neoplasia (CIN) in 43 (62.3%) cases, of which high-grade CIN accounted for 24 (34.8%) cases. There was good correlation between cytologic and histologic diagnosis. Simple regression analysis showedr= 0.46,P< 0.0001. The cytologic abnormality was highly predictive of the corresponding histologic diagnosis. This analysis has shown that significant intraepithelial lesions may exist despite negative colposcopic examination and highlights the need for histologic evaluation in such cases. In these circumstances, loop cone biopsy permits accurate definition of lesion severity, avoids potential undertreatment of significant lesions and causes less morbidity than conventional cone biopsy.

scholarly journals Definition of essential sequences and functional equivalence of elements downstream of the adenovirus E2A and the early simian virus 40 polyadenylation sites.

1985 ◽  
Vol 5 (11) ◽  
pp. 2975-2983 ◽  
Author(s):  
R P Hart ◽  
M A McDevitt ◽  
H Ali ◽  
J R Nevins
Keyword(s):  
Essential Element ◽  
Simian Virus 40 ◽  
Simian Virus ◽  
Cleavage Sites ◽  
Multiple Sequence ◽  
Polyadenylic Acid ◽  
Sequence Elements ◽  
Cleavage And Polyadenylation ◽  
Definition Of ◽  
A Site

In addition to the highly conserved AATAAA sequence, there is a requirement for specific sequences downstream of polyadenylic acid [poly(A)] cleavage sites to generate correct mRNA 3' termini. Previous experiments demonstrated that 35 nucleotides downstream of the E2A poly(A) site were sufficient but 20 nucleotides were not. The construction and assay of bidirectional deletion mutants in the adenovirus E2A poly(A) site indicates that there may be redundant multiple sequence elements that affect poly(A) site usage. Sequences between the poly(A) site and 31 nucleotides downstream were not essential for efficient cleavage. Further deletion downstream (3' to +31) abolished efficient cleavage in certain constructions but not all. Between +20 and +38 the sequence T(A/G)TTTTT was duplicated. Function was retained when one copy of the sequence was present, suggesting that this sequence represents an essential element. There may also be additional sequences distal to +43 that can function. To establish common features of poly(A) sites, we also analyzed the early simian virus 40 (SV40) poly(A) site for essential sequences. An SV40 poly(A) site deletion that retained 18 nucleotides downstream of the cleavage site was fully functional while one that retained 5 nucleotides downstream was not, thus defining sequences required for cleavage. Comparison of the SV40 sequences with those from E2A did not reveal significant homologies. Nevertheless, normal cleavage and polyadenylation could be restored at the early SV40 poly(A) site by the addition of downstream sequences from the adenovirus E2A poly(A) site to the SV40 +5 mutant. The same sequences that were required in the E2A site for efficient cleavage also restored activity to the SV40 poly(A) site.

Theism and Hypertheism

1943 ◽  
Vol 36 (1) ◽  
pp. 63-81
Author(s):  
John Laird
Keyword(s):  
Accurate Definition ◽  
Definition Of

Theists, I suppose, are persons who believe in “God's” existence. Atheists are persons who deny the same.Such statements may be suitable, and even adequate, for many proper purposes. In several contexts it is silly or malicious to interrogate them closely. Even in theology, which is, or should be, some kind of science, they may have, and they do have, their use and their propriety. For many theological purposes, however (and also for some others) they are far too vague. It may be wrong, no doubt, to tell a theologian that he must either produce an accurate definition of what he means by “God” or be forever shamed.

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