Here, we demonstrate that the active conformation of the CDR loops of natural antibodies can be reconstructed on AuNPs to create Goldbodies, which bind the corresponding antigens specifically with apparent affinities several orders of magnitude stronger than those of the original natural antibodies. Up to now, both NP functionalization (4⇓⇓⇓-8) and protein mimicking (48) have relied on the incorporation of functional groups. Herein we show that new functions of NPs can be created by controlling the conformation of the surface groups on NPs. Self-assembled monolayers on gold surfaces have shown certain molecular density effects on the packing of the immobilized groups (49⇓-51), yet those self-assembling methods aim to create certain macro patterns consisting of numerous chains. Precisely manipulating conformations of individual groups for specific functions is still beyond reach. The seemingly insurmountable task of tuning the conformation of individual peptides for specific ...
The target of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (Abs) is the putative trimer of gp120-gp41 heterodimers that decorates the surface of HIV-1 (10, 28, 43, 52, 54). In the case of gp41, it appears that antibody access to neutralizing epitopes may be more restricted than access to those on gp120, since the relevant epitopes on gp41 probably become fully exposed only during HIV-1 envelope-mediated virus-cell membrane fusion (4, 19, 20, 46). The two anti-gp41 monoclonal Abs (MAbs) that are the most potent and broadly neutralizing are the human immunoglobulin G (IgG) MAbs 2F5 and 4E10 (12, 14, 16, 21, 47, 49, 58). The core epitope of 2F5, the most studied of the two MAbs, has been defined conveniently by a short linear sequence, ELDKWA, which is found at the extreme C-terminal end of the C-heptad repeat region on the ectodomain of gp41 (37). MAb 4E10 appears to recognize an epitope immediately C-terminal to the 2F5 epitope. The 4E10 epitope has been defined by the ...
This study investigated whether fingolimod reduced newly produced T and B lymphocytes and T-cell receptor repertoire diversity in peripheral blood in patients
Next-generation sequencing enabled T-cell receptor (TCR) repertoire analysis has gained major attention in scientific as well as clinically driven research. However, despite improvements of sequencing technology, next-generation sequencers produce huge data sets that are usually prone to errors, thus urging the need for improved analysis tools being able to account not only for the large number of sequences but also for sequencing artifacts. TCRProfiler is a tool that includes sequencer generated quality values to improve reliability of TCR repertoire analysis. As a stand alone tool for parallel and detailed analysis, TCRProfiler delimits combinatorial diversity (rearranged germline V, (D), and J genes) and junctional diversity (P(alindromic)-, and N(on-template)-nucleotides) of TCR alpha and/or beta chain sequences. TCRProfiler generates probe-specific statistical repertoire profiles, as well as visualization files to allow fast and comprehensive accession of repertoire diversity. In a single ...
Novelty: Unbiased analysis of immunophenotyping of blood from a cohort of moderate, severe, recovered COVID-19 donors and healthy control reveals selective clustering of severe individuals. Severe cases have oligoclonal expansion of antibodies, which have long CDR3s, indicating multi-reactivity, compared to moderate cases that had a more diverse clonal expansion. The increased frequencies of neutrophil and eosinophil populations were not associated with an activated phenotype. They highlight a decrease of CD15 expression in neutrophils and CD16 expression in different innate immune cell populations such as NK cells that could be interesting to investigate further. Standing in the field: They show extensive data on blood immune cell composition between different subgroups of COVID-19 patients that supports other studies, which they always cite. Appropriate statistics: The statistical tools used are very clear and all listed in the method section of the paper. Viral model used: SARS-CoV2 from ...
Urethane on Poly wheel utilizes polyurethane mechanically bonded to a high-density polypropylene core. This mechanical bond eliminates bond separation due to
For CDR3 size polymorphism analysis we used the Immunoscope software package. 23 Immunoscope analysis couples fluorescence PCR and software analysis and allows the direct and accurate sizing of a clonal population of T or B cells within a polyclonal milieu. Peripheral blood mononuclear cells (PBMCs) were prepared by centrifugation on single-density gradient (Ficoll Hypaque; Pharmacia, Upsala, Sweden) and processed for Immunoscope analysis, as previously described. 25 An Epstein-Barr virus (EBV)-transformed human B lymphoblastoid cell line (BLCL) was established in the laboratory and maintained as previously described. 26 The vitreous humor was obtained after vitrectomy. Approximately 200 μL of vitreous humor was diluted in a saline solution to a final volume of 1 mL, and the samples were centrifuged immediately (910g for 10 minutes at 4°C). Previous morphologic studies revealed that such amounts of vitreous humor obtained from PIOL patients contain, on average, 1000 cells (Merle-Beral H, ...
Antibodies can rapidly evolve in specific response to antigens. Affinity maturation drives this evolution through cycles of mutation and selection leading to enhanced antibody specificity and affinity. Elucidating the biophysical mechanisms that underlie affinity maturation is fundamental to understanding B-cell immunity. An emergent hypothesis is that affinity maturation reduces the conformational flexibility of the antibodys antigen-binding paratope to minimize entropic losses incurred upon binding. In recent years, computational and experimental approaches have tested this hypothesis on a small number of antibodies, often observing a decrease in the flexibility of the Complementarity Determining Region (CDR) loops that typically comprise the paratope and in particular the CDR-H3 loop, which contributes a plurality of antigen contacts. However, there were a few exceptions, and previous studies were limited to a small handful of cases. Here, we determined the structural flexibility of the CDR-H3 loop
CD4 T lymphocyte activation requires T cell receptor (TCR) engagement by peptide/MHC (major histocompatibility complex) (pMHC). The TCR complementarity-determining region 3 (CDR3) contains variable α and β loops critical for pMHC recognition. During any immune response, tuning of TCR usage through progressive clonal selection occurs. Th1 and Th2 cells operate at different avidities for activation and display distinct transcriptional programs, although polarization may be plastic, influenced by pathogens and cytokines. We therefore hypothesized that CDR3αβ sequence features may intrinsically influence CD4 phenotype during progression of a response. We show that CD4 polarization involves distinct CDR3α usage: Th1 and Th17 cells favored short TCR CDR3α sequences of 12 and 11 amino acids, respectively, while Th2 cells favored elongated CDR3α loops of 14 amino acids, with lower predicted affinity. The dominant Th2- and Th1-derived TCRα sequences with14 amino acid CDR3 loops and 12 amino acid CDR3
Lesk has made significant contributions to the study of protein evolution.[2] He and Cyrus Chothia, working at the Medical Research Council (UK) Laboratory of Molecular Biology in Cambridge, United Kingdom, discovered the relationship between changes in amino-acid sequence and changes in protein structure by analyzing the mechanism of evolution in protein families.[3][4] This discovery has provided the quantitative basis for the most successful and widely used method of structure prediction, known as homology modelling. Lesk and Chothia also studied the conformations of antigen-binding sites of immunoglobulins. They discovered the canonical-structure model for the conformation of the complementarity-determining regions of antibodies, and they applied this model to the analysis of antibody-germ-line genes, including the prediction of the structure of the corresponding proteins. This work has supported the humanization of antibodies for therapy in the treatment of cancer. This approach to ...
The antigen-binding end of an antibody molecule and green fluorescent protein (GEP) both contain β-strands that are connected by exposed loops. Zeytun et al. have taken advantage of this commonality and engineered libraries of fluorobodies by inserting antigen-binding sequences (the complementarity-determining regions) within four of the GFP loops. They isolated fluorobodies that bound specifically to several proteins (ubiquitin, tubulin, and myoglobin) with submicromolar affinities and were used successfully in immunofluorescence microscopy, immunoblots, or flow cytometry. - GJC. NatureBiotechnol. 10.1038/nbt911 (2003).. ...
branch: master commit 8f5738eb8fc7556b69016976dfa810f7e6275bf8 Author: Lars Ingebrigtsen ,[email protected], Commit: Lars Ingebrigtsen ,[email protected], Add more car/cdr examples to shortdoc * lisp/emacs-lisp/shortdoc.el (list): Add more car/cdr examples. --- lisp/emacs-lisp/shortdoc.el , 8 ++++++-- 1 file changed, 6 insertions(+), 2 deletions(-) diff --git a/lisp/emacs-lisp/shortdoc.el b/lisp/emacs-lisp/shortdoc.el index dbf1696..3a32f63 100644 --- a/lisp/emacs-lisp/shortdoc.el +++ b/lisp/emacs-lisp/shortdoc.el @@ -503,9 +503,13 @@ There can be any number of :example/:result elements. (flatten-tree :eval (flatten-tree (1 (2 3) 4))) (car - :eval (car (one two three))) + :eval (car (one two three)) + :eval (car (one . two)) + :eval (car nil)) (cdr - :eval (cdr (one two three))) + :eval (cdr (one two three)) + :eval (cdr (one . two)) + :eval (cdr nil)) (last :eval (last (one two three))) (butlast ...
Surface representation of the CDRs.(A) Surface representation of D7 revealing the gp120 docking interface based on gp120 binding and HIV-1 neutralization result
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title: T 세포 백혈병 세포주에서 T 세포 수용체 β쇄 CDR3 유전자 염기서열의 규명, doi: none, category: Thesis
The analysis of the T cell repertoires involved in local or systemic immune responses is beginning to play an important role in many clinical situations. These include autoimmunity, response to viral or bacterial superantigens, alloimmunity including allograft rejection, and tumor immunity. Here we analyze circulating T cell repertoires by determining TCR beta-chain gene complexity using a modification of V beta family-specific PCR. This approach, called CDR3 size spectratyping, uses the size heterogeneity of the CDR3 as a further source of specificity in TCR analysis. It has been used here to analyze the complexity and stability of circulating T cell repertoires in normal adults, including bone marrow donors, and bone marrow transplant recipients. Normal spectratypes are both complex and stable. The repertoire complexity of marrow recipients correlates with their state of immune function. Contractions and gaps in repertoires are revealed in individuals suffering from recurrent infections ...
The intestinal mucosa is constantly exposed to microbial and dietary antigens, all of which are considered to induce IgA-secreting plasma cells. Thus, the limited IgA repertoire diversity predicted in previous studies (Dunn-Walters et al., 1997, 2000; Holtmeier et al., 2000; Stoel et al., 2005; Yuvaraj et al., 2009) is difficult to reconcile with the broad range of intestinal antigens. In this study, we show that in fact each individual harbors a private polyclonal and highly diverse IgA repertoire. Because we analyzed switched Ig sequences, repertoire analyses performed in this study did not require sorting of plasma cells. Instead, RNA was isolated directly from intestinal tissue, and IgA-encoding transcripts were enriched during reverse transcription. This approach was equivalent to our results obtained when RNA was isolated out of sorted plasma cells. The IgA repertoire showed characteristics reminiscent of the T cell receptor repertoire of CD8+ memory cells (Naumov et al., 2003), i.e., the ...
T-cell receptor repertoires could help researchers determine whether a certain treatment will work for a given cancer patient. 
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B cell antigen receptor (BCR) or antibody diversity arises from somatic recombination of immunoglobulin (Ig) gene segments and is concentrated within the Ig heavy (H) chain complementarity-determining region 3 (CDR-H3). We performed high-throughput sequencing of the expressed antibody heavy chain repertoire from adult torafugu. We found that torafugu use between 70% and 82% of all possible V (variable) D (diversity) J (joining) gene segment combinations and that they share a similar frequency distribution of these VDJ combinations. The CDR-H3 sequence repertoire observed in individuals is biased with the preferential use of a small number of VDJ, dominated by sequences containing inserted nucleotides. We uncovered the common CDR-H3 amino acid (aa) sequences shared by individuals. Common CDR-H3 sequences feature highly convergent nucleic acid recombination compared with private ones. Finally, we observed differences in repertoires between IgM and IgT, including the unequal usage frequencies of V gene
T cells play an important role in the pathogenesis of systemic lupus erythematosus (SLE). Clonal expansion of T cells correlating with disease activity has been observed in peripheral blood (PB) of SLE subjects. Recently, next-generation sequencing (NGS) of the T cell receptor (TCR) β loci has emerged as a sensitive way to measure the T cell repertoire. In this study, we utilized NGS to assess whether changes in T cell repertoire diversity in PB of SLE patients correlate with or predict changes in disease activity. Total RNA was isolated from the PB of 11 SLE patients. Each subject had three samples, collected at periods of clinical quiescence and at a flare. Twelve age-matched healthy controls (HC) were used for reference. NGS was used to profile the complementarity-determining region 3 (CDR3) of the rearranged TCR β loci. Relative to the HC, SLE patients (at quiescence) demonstrated a 2.2-fold reduction in repertoire diversity in a given PB volume (P |0.0002), a more uneven distribution of the
The diversity of the human TCR repertoire in aging has been studied by examining the profiles of complementarity-determining region 3 (CDR3) sizes expressed by the BV families. The TCRBV CDR3 profile, which shows size heterogeneity in young adult humans, is significantly restricted in aged humans. Clonal T cell expansions were identified using a PCR-based approach, in one or more BV families from all 14 healthy persons over the age of 65 that we studied. CD4+ T cell expansions were identified in 8 of 11 donors and CD8+ T cell expansions in 7 of 10 donors. These clonal expansions were stable during a 2-year period. Interestingly, more than half of the aged persons had clonal expansions within the BV3, -14, -16, and -23 families. Although there was no homology among the eight CDR3 sequences identified in clonal T cells from 8 aged persons, selective pressure on the expanded T cell clones was suggested by the fact that the BV families used by the T cell clones were not proportional to the number of ...
Downloadable! Empirical research on complementarity between organizational design decisions has traditionally focused on the question of existence of complementarity. In this paper, we take a broader approach to the issue, combining a productivity and an adoption approach, while including a search for contextual variables in the firms strategy that affects complementarity. Analysis of contextual variables is not only interesting per se, but also improves the productivity test for the existence of complementarity. We use our empirical methodology to analyze complementarity between innovation activities: internal research and development (R& D) and external knowledge acquisition. Our results suggest that internal R& D and external knowledge acquisition are complementary innovation activities, but that the degree of complementarity is sensitive to other elements of the firms strategic environment. We identify reliance on basic R& D--the importance of universities and research centers as an
1. The regulation of the immune response: vaccine design, phage-based vaccines, Virus-like-particle vaccines, protein vaccines, Alzheimers Disease immunotherapy, induction of immune responses to self-antigens, correlates of vaccine efficacy, signaling in T cell development and activation, T cell receptor repertoire in Coeliac disease, T cell receptor repertoire of antigen-specific T cell lines ...
functions (append (car display-buffer-overriding-action) , (car user-action) , (car action) , (car display-buffer-default-action))) , (alist (append (cdr display-buffer-overriding-action) , (cdr user-action) , (cdr action) , (cdr display-buffer-default-action)))) , (run-with-args-until-success functions buffer alist))) Elaborating once more on this subject: Let O, U, A and D respectively denote the functions in the cars of display-buffer-overriding-action, user-action, action, and display-buffer-default-action and OL, UL, AL, DL the alists in the corresponding cdrs. Now my original proposal was to run until success (O . (OL UL AL DL)) (U . (UL AL DL)) (A . (AL DL)) (D . (DL)) that is, try the overriding function with all alists, if that fails try the user function with all alists but the overriding one and so on. People raised concerns about misinterpreting the alist concept and Chong proposed to do something like (O . (OL)) (U . (UL)) (A . (AL)) (D . (DL)) instead. I raised concerns about ...
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Use the search fields below to explore our most up to date test repertoire and find user details such as how to order and interpret results. ...
1. Its possible and instructive to build repertoire by adding one tune a week and concentrating my practicing and playing to these tunes. Yes, indeed. I...
Material and methods Three DMARD-naïve ERA patients (disease duration , 1 year) and three ESRA patients (disease duration ,2 years) were included. All fulfilled the American College of Rheumatology1987 criteria for RA. mRNA was isolated from paired ST and PB samples. A linear amplification with primers for all V(ariable)-genes of the T cell receptor β-chain was performed. The amplified products contain the CDR3s of all T cells. Samples were processed using a Genome Sequencer (454) analysing up to 15 000 receptors per sample, The frequency of each clone was determined by its CDR3 frequency (% of all CDR3s analysed). Clones with a CDR3 frequency of ,1% were arbitrarily considered as highly expanded clones (HECs).. ...
In this report, we describe the molecular and functional characterization of T-cell clones identified in peripheral blood from patients with relapsed myeloma responding to DLI. These clones were initially identified through analysis of TCR Vβ repertoire (spectratyping), a technique that provides a comprehensive characterization of the circulating T-cell compartment (21 , 24 , 25) . Serial analysis of T-cell repertoire in patient samples has also been used to detect the emergence of oligoclonal and clonal T cells at different times in vivo (18 , 26 , 27) . By combining analysis of TCR repertoire with clinical events, we observed the expansion of individual T-cell clones in peripheral blood that were temporally associated with the initiation of either a GVM or GVHD response (17) . However, despite the association of these T-cell clones with specific clinical responses, the functional specificity of these T cells was not established. Further studies were therefore undertaken to quantify the ...
There is a reason this project is unique. It is because governments and regulators in other countries see no reason to collect every single CDR for every single call. If others do not have a system like this, how can Malawis authorities make extraordinary promises about improving services as well as gathering more taxes?. Awareness of the perils of CDR collection has moved on since MACRA initiated their project, even if MACRAs arguments have not changed at all. The world can turn its eyes toward the example set by the USA, whose authorities also needed to justify blanket collection of CDRs. In that case, the leak of secret court orders revealed that the NSA was gathering huge swathes of call data. The subsequent justification offered by the NSA was that the data is needed to identify relationships between potential terrorists. In other words, the NSA gathers CDRs for the purpose of surveillance. Meanwhile, Malawis government says they will implement a comprehensive centralized database of ...
DI-fusion, le Dépôt institutionnel numérique de lULB, est loutil de référencementde la production scientifique de lULB.Linterface de recherche DI-fusion permet de consulter les publications des chercheurs de lULB et les thèses qui y ont été défendues.
China, as expected, has remained the largest source of Indias imports in 2020, highlighting the economic complementarities of the two Asian economies which is exactly what could help India to promote its
It is precisely at the problematic crossroads so often encountered in relationships that we are offered the opportunity to create a new foundation based on mutual complementarity rather than need; a free relationship between two people who want to be together, rather than two people who need to be together. Needing another, we are told, is the measure of love, but for a fully conscious individual nothing could be further from the truth. And therein lies part of the secret and healing power of spiritual partnerships. ...
Human cytomegalovirus (HCMV) infections are life-threating to people with a compromised or immature immune system. Upon adhesion, fusion of the virus envelope with the host cell is initiated. In this step, the viral glycoprotein gB is considered to represent the major fusogen. Here, we present for the first time structural data on the binding of an anti-herpes virus antibody and describe the atomic interactions between the antigenic domain Dom-II of HCMV gB and the Fab fragment of the human antibody SM5-1. The crystal structure shows that SM5-1 binds Dom-II almost exclusively via only two CDRs, namely light chain CDR L1 and a 22-residue-long heavy chain CDR H3. Two contiguous segments of Dom-II are targeted by SM5-1, and the combining site includes a hydrophobic pocket on the Dom-II surface that is only partially filled by CDR H3 residues. SM5-1 belongs to a series of sequence-homologous anti-HCMV gB monoclonal antibodies that were isolated from the same donor at a single time point and that ...
0094] Clonotype profile means a listing of distinct clonotypes and their relative abundances that are derived from a population of lymphocytes. Typically, the population of lymphocytes are obtained from a tissue sample. The term clonotype profile is related to, but more general than, the immunology concept of immune repertoire as described in references, such as the following: Arstila et al. Science, 286: 958-61 (1999): Yassai et al. Imnunogenetics, 61: 493-502 (2009); Kedzierska et al, Mol. Immunol., 45(3): 607-618 (2008); and the like. The term clonotype profile includes a wide variety of lists and abundances of rearranged immune receptor-encoding nucleic acids, which may be derived from selected subsets of lymphocytes (e.g. tissue-infiltrating lymphocytes, immunophenotypic subsets, or the like), or which may encode portions of immune receptors that have reduced diversity as compared to full immune receptors. In some embodiments, clonotype profiles may comprise at least 103 distinct ...
We will carry out deep sequencing of rearranged immunoglobulin (Ig) and T cell receptor (TCR) genes from lymphocytes in human subjects responding to several dis...
We will carry out deep sequencing of rearranged immunoglobulin (Ig) and T cell receptor (TCR) genes from lymphocytes in human subjects responding to several dis...
Its this seemingly paradoxical and yet crucial yin-and-yang aspect of science that I believe is still quite hard to grasp for non-scientists. Niels Bohr would have appreciated the tension. Bohr bequeathed to the world the concept of complementarity. Complementarity means the existence of seemingly opposite ideas that are still required together to explain the world. In the physical world, complementarity was first glimpsed in the behavior of subatomic particles which can sometimes behave as waves and sometime as particles, depending on the experiment. Waves and particles may seem to be contradictory concepts, and yet as the pioneers of quantum mechanics showed us, you cannot explain reality without assuming that electrons or photons are both. In his later life, Bohr extended the idea of complementarity to many aspects of the human world; good and evil, freedom and restraint, war and peace. He realized that all of these seemingly paradoxical aspects of the human and physical world have to ...
pI profiles across HC CDR3 regions of NZM2410-derived ANAs and non-ANAs. The mean pI value (isoelectric point) at each HC CDR3 position (from H95 to H100a) was
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Use 80 min. / 730 MB Cdr where nessecary !!. I can copy all of my recordings to CDr. If Its from LP or tape/video you can be sure its remastered before I make a Cdr of it. So NO crackles from boot LPs on my Cdrs!!!! ...
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Immunoglobulins play important roles in antigen recognition during the immune response, and the complementarity-determining region (CDR) 3 of the heavy chain is considered as the critical antigen-binding site. We previously developed a statistical protocol for the extensive analysis of heavy chain variable region repertoires and the dynamics of their immune response using next-generation sequencing (NGS). The properties of important antibody heavy chains predicted in silico by the protocol were examined by gene synthesis and antibody protein expression; however, the corresponding light chain that matches with the heavy chain could not be predicted by our protocol. To understand the dynamics of the heavy chain and the effect of light chain pairing on it, we firstly tried to obtain an artificial light chain that pairs with a broad range of heavy chains and then analyzed its effect on the antigen binding of heavy chains upon pairing. During the pre-B cell stage, the surrogate light chain (SLC) ...
Backwash is a ten-year compilation of Wayne Butanes talk-heavy plunderphonics collages. It collects seven cassette recordings and one seven-inch record into one long CDR track. The work is somewhat akin to the less musical side of People Like Us and The Tape Beatles, with emphasis on vocal clips rather than song excerpts - which are also present, but sparse. Like Swipes, which I also reviewed recently, this disc is successful because of its sample diversity - theres so much on here, that you just end up sitting next to the stereo with your mouth gaping open in awe. Sound sources come from everywhere - grisly newscasts, Michael Jackson, Longmont Potion Castle, and even pornography. This isnt nearly as polished as some of the more popular audio collage material, but its a good selection of lo-fi cut-n-pasting. Fun.. 85%. Matt Shimmer ...
We have humanized a murine anti-GM2 MAb in an attempt to improve its potential clinical efficacy by reducing its immunogenicity and by changing the C region to support potent CDC and ADCC. The pharmacokinetic studies of humanized MAbs and murine MAbs in monkeys revealed that the humanization resulted in a prolonged serum half-life and in a substantial reduction in immunogenicity compared with the murine MAbs (44 , 45) . The antihumanized KM8969 response would be theoretically directed to a conformational epitope formed by the CDR loops, so that the reduction in immune response to the KM8969 in monkeys and humans would be expected in comparison with the chimeric KM966, which has murine V regions including CDRs. There has been no comparative pharmacokinetic studies between the humanized MAbs and their counterpart chimeric MAbs. The actual advantages of the humanized MAbs in pharmacokinetics vary for each MAb and need to be evaluated in clinical studies.. The humanized KM8969 showed a binding ...
Repertoire Bibliographique Des Principales Revues Francaises, by Daniel Jordell, 9781236769947, available at Book Depository with free delivery worldwide.