576 research outputs found
The solution structure of the human IgG2 subclass is distinct from those for human IgG1 and IgG4 providing an explanation for their discrete functions
No full textHuman IgG2 antibody displays distinct therapeutically-useful properties compared with the IgG1, IgG3 and IgG4 antibody subclasses. IgG2 is the second most abundant IgG subclass, being able to bind human FcγRII/FcγRIII, but not to FcγRI or complement C1q. Structural information on IgG2 is limited by the absence of a full-length crystal structure for this. To this end, we determined the solution structure of human myeloma IgG2 by atomistic X-ray and neutron scattering modelling. Analytical ultracentrifugation disclosed that IgG2 is monomeric with a sedimentation coefficient s020,w of 7.2 S. IgG2 dimer formation was ≤ 5% and independent of the buffer conditions. Small-angle X-ray scattering in a range of NaCl concentrations and in light and heavy water revealed that the X-ray radius of gyration Rg is 5.2-5.4 nm, after allowing for radiation damage at higher concentrations, and that the neutron Rg value of 5.0 nm remained unchanged in all conditions. The X-ray and neutron distance distribution curves P(r) revealed two peaks, M1 and M2, that were unchanged in different buffers. The creation of ˃123,000 physically-realistic atomistic models by Monte Carlo simulations for joint X-ray and neutron-scattering curve fits, constrained by the requirement of correct disulfide bridges in the hinge, resulted in the determination of symmetric Y-shaped IgG2 structures. These molecular structures were distinct from those for asymmetric IgG1 and asymmetric and symmetric IgG4, and were attributable to the four hinge disulfides. Our IgG2 structures rationalize the existence of the human IgG1, IgG2, and IgG4 subclasses, and explain the receptor binding functions of IgG2
Henri Temianka Correspondence; (de Gar)
No full textThis collection contains material pertaining to the life, career, and activities of Henri Temianka, violin virtuoso, conductor, music teacher, and author. Materials include correspondence, concert programs and flyers, music scores, photographs, and books.https://digitalcommons.chapman.edu/temianka_correspondence/1805/thumbnail.jp
Unravelling the interaction of the human IgG subclasses with their ligands using biophysical methods
No full textAntibodies are responsible for binding to antigens through their Fab arms and eliciting an immune response by binding to Fcγ receptors (FcγR). IgG4 is associated with IgG4-related disease. Human IgG in blood consists of four subclasses (IgG1, IgG2, IgG3 and IgG4). In order to identify their solution structures, monoclonal IgG1 and IgG4 and myeloma IgG2 were studied using analytical ultracentrifugation (AUC) and small-angle X-ray and neutron scattering (SAXS, SANS), followed by atomistic modelling using molecular dynamics and Monte Carlo methods. The three IgG subclasses exhibit variable conformations and flexibility, reflecting their function. FcγRI (CD64) is the sole high-affinity human IgG receptor. Its crystal structure showed that its three domains D1, D2 and D3 form a compact “seahorse” shape. To identify its solution structure, AUC and SAXS data and their modelling showed that FcγRI is more elongated than its crystal structure, in which the D1 and D2 domains were no longer in contact with each other, and the D3 domain showed flexibility. The solution structures of the IgG1 and IgG4 complexes with FcγRI were determined by AUC, SAXS and SANS. These showed a 1:1 binding stoichiometry. Their atomistic modelling showed that the Fc region in IgG1/IgG4 accommodates one FcγRI asymmetrically, and the two Fab arms were displaced to enable FcγRI binding. The modelling showed that the bound FcγRI changed conformation back into a compact “seahorse” where D1 is folded back against the D2 domain. Here, the solution structure of full-length IgG with FcγRI resembled the crystal structures of the IgG Fc fragment complexes with FcγRI. It was concluded that the folding back of FcγRI into a “seahorse” conformation ensures 1:1 binding and high-affinity interaction, giving an effective and regulated immune response to remove foreign antigens. This thesis furthers our understanding of the conformations of human IgG and their association with disease
Allosteric role of the amino-terminal A/B domain on corticosteroid transactivation of gar and human glucocorticoid receptors
No full textWe studied the role of the A/B domain at the amino terminus of gar (Atractosterus tropicus) and human glucocorticoid receptors (GRs) on transcriptional activation by various glucocorticoids. In transient transfection assays, dexamethasone [DEX] and cortisol had a lower half-maximal response (EC50) for transcriptional activation of full length gar GR than of human GR. Both GRs had similar responses to corticosterone, while 11-deoxycortisol had a lower EC50 for gar GR than for human GR. In contrast, constructs of gar GR and human GR consisting of their hinge (D domain), ligand binding domain (LBD) (E domain) fused to a GAL4 DNA-binding domain (DBD) had a higher EC50 (weaker response) for all glucocorticoids. To study the role of the A/B domain, which contains an intrinsically disordered region, we investigated steroid activation of chimeric gar GR and human GR, in which their A/B domains were exchanged. Replacement of human A/B domains with the gar A/B domains yielded a chimeric GR with a lower EC50 for DEX and cortisol, while the EC50 increased for these steroids for the human A/B-gar C/E chimera, indicating that gar A/B domains contributes to the lower EC50 of gar GR for glucocorticoids. Our data suggests that allosteric signaling between the A/B domains and LBD influences transcriptional activation of human and gar GR by different steroids, and this allosteric mechanism evolved over 400 million years before gar and mammals separated from a common ancestor. (C) 2015 Elsevier Ltd. All rights reserved
The parasite fauna of gar-fish - Belone belone (L.) from Puck Bay
No full textFrom 1966 to 1967 the author carried out an investigation on the helminth fauna of gar-fish Belone belone (L.) from Puck Bay of the Baltic. It was established, the next species parasitise in gar-fish: Diplostomum spathaceum (Rud.), Tylodelphys sp., Scolex pleuronectis Mull., Contracaecum aduncum (Rud.), Cucullanus truttae (Fabricius), Pomphorhynchus laevis (Zoega), and Neoechinorhynchus rutili (Mull.). With exception of Pomphorhynchus laevis (Zoega) they were not found in gar-fish yet, but they occur commonly in the other Polish fishes
Effects of Temperature and Light on Aerial Breathing of the Longnose Gar, Lepisosteus Osseus
No full textAuthor Institution: Department of Zoology, University of OklahomaSAKSENA, VISHNU P. Effects of temperature and Light on Aerial Breathing of the Longnose Gar, Lepisosteus osseus. Ohio J. Sci. 72(1): 58, 1975
Les composés à rection verbale en gallois et le problème des formations en -gar
No full textCompound with verbal head in Welsh and the problem of -gar derivatives.
It is remarkable that Welsh (and probably also all Celtic languages) has kept all the types of nominal composition, given the other typological changes which happened in this dialect of Indo-European. The author takes the example of Welsh compounds with verbal head (Greek type φερέ-οικος, βου-πλήξ Vedic trasá-dasyu- et viśva-víd-) : their formation, syntactical behaviour, and the productivity of two sub-types are shown with significant examples. A special case, the derivatives with -gar, is discussed at length, because it is still a living formation. Its semantic ambiguity is explained by its double origin.La conservation de tous les types de composition nominale en gallois (et probablement dans les langues celtiques en général) est remarquable compte tenu des autres changements typologiques de cette branche de l’Indo-Européen. On expliquera par exemple les composés gallois à rection verbale (du type grec φερέ-οικος et βου-πλήξ, védique trasá-dasyu- et viśva-víd-) : leur formation et comportement syntaxique, ainsi que la productivité de deux sous-types seront démontrés à l’aide d’exemples représentatifs. Un cas spécial, les formations en -gar, est discuté en détail, parce qu’il est toujours vivant. Son ambiguité sémantique sera expliquée sur la base d’une double origine formelle.Zimmer Stefan. Les composés à rection verbale en gallois et le problème des formations en -gar. In: Etudes Celtiques, vol. 29, 1992. Actes du IXe congrès international d'études celtiques. Paris, 7-12 juillet 1991. Deuxième partie : Linguistique, littératures. pp. 441-451
The generalized asymmetric rule (GAR): The optimization of mixture asymmetry in a noncubic equation of state.
No full textThis work uses a preexisting, noncubic EOS to predict polar/nonpolar pure components. This EOS uses the mixing rules of a preexisting local composition model (LCM) that can simultaneously (1) simulate both liquid and vapor compositions and (2) employ one (or more) pure-component equation(s) of state. The practical application entailed composition predictions of natural-gas dehydrators, including pure-component vapor-pressure and liquid-density simulations for ethylene glycol, diethylene glycol, triethylene glycol, five aromatic compounds, and two freons.This work introduces the generalized asymmetric rule (GAR) for equation-of-state (EOS) models. The GAR constitutes a novel equation that models unlike-interaction parameters (UIPs) in the simulation of vapor-liquid equilibrium (VLE) mixture compositions.A third appendix details limiting cases of both the GSR and GAR; a fourth appendix lists literature sources of mixture data, including VLE and other thermodynamic properties. Finally, the dissertation also lists pure-component property sources including vapor pressure, liquid density, enthalpy, and other thermodynamic properties.The GAR was developed by the author of this work and can replace binary interaction parameters (BIPs), a long-recognized UIP modeling standard. Overall, GARs present three basic advantages: First, GARs can provide up to a three-dimensional representation, or "mapping, " of binary systems in lieu of one-dimensional BIP representations. Second, GARs indicate how much one component "outweighs" another for a given UIP. Third, GARs offer a nondivergent mechanism that guarantees a reliable asymmetry model for UlPs.The GAR can average numbers of positive, negative, and/or zero numerical values. Moreover, the GAR can invoke positive/negative sign changes for numbers of like and/or unlike signs. The GAR therefore holds potential for other fields whenever any given set of numbers must be averaged asymmetrically.Overall, GARs surpassed BIN in over half of all results. Furthermore, this work briefly reviews literature methods that can overcome limitations of insufficient ternary binary VLE data. These methods include the use of (1) solubility data, (2) ternary data, (3) other thermodynamic property data, (4) infinite-dilution activity coefficients, (5) the substitution of alternate isomeric-component data, and (6) interpolation with the GAR. Two appendices suggest future methods of binary/multicomponent VLE modeling and overcoming parameter-correlation problems
Neural-based Knowledge Transfer in Natural Language Processing
No full textIn Natural Language Processing (NLP), neural-based knowledge transfer, which is to transfer out-of-domain (OOD) knowledge to task-specific neural networks, has been applied to many NLP tasks. To further explore neural-based knowledge transfer in NLP, in this dissertation, we consider both structured OOD knowledge and unstructured OOD knowledge, and deal with several representative NLP tasks. For structured OOD knowledge, we study the neural-based knowledge transfer in Machine Reading Comprehension (MRC). In single-passage MRC tasks, to bridge the gap between MRC models and human beings, which is mainly reflected in the hunger for data and the robustness to noise, we integrate the neural networks of MRC models with the general knowledge of human beings embodied in knowledge bases. On the one hand, we propose a data enrichment method, which uses WordNet to extract inter-word semantic connections as general knowledge from each given passage-question pair. On the other hand, we propose a novel MRC model named Knowledge Aided Reader (KAR), which explicitly uses the above extracted general knowledge to assist its attention mechanisms. According to the experimental results, KAR is comparable in performance with the state-of-the-art MRC models, and significantly more robust to noise than them. On top of that, when only a subset (20%-80%) of the training examples are available, KAR outperforms the state-of-the-art MRC models by a large margin, and is still reasonably robust to noise. In multi-hop MRC tasks, to probe the strength of Graph Neural Networks (GNNs), we propose a novel multi-hop MRC model named Graph Aided Reader (GAR), which uses GNN methods to perform multi-hop reasoning, but is free of any pre-trained language model and completely end-to-end. For graph construction, GAR utilizes the topic-referencing relations between passages and the entity-sharing relations between sentences, which is aimed at obtaining the most sensible reasoning clues. For message passing, GAR simulates a top-down reasoning and a bottom-up reasoning, which is aimed at making the best use of the above obtained reasoning clues. According to the experimental results, GAR even outperforms several competitors relying on pre-trained language models and filter-reader pipelines, which implies that GAR benefits a lot from its GNN methods. On this basis, GAR can further benefit from applying pre-trained language models, but pre-trained language models can mainly facilitate the within-passage reasoning rather than cross-passage reasoning of GAR. Moreover, compared with the competitors constructed as filter-reader pipelines, GAR is not only easier to train, but also more applicable to the low-resource cases. For unstructured OOD knowledge, we study the neural-based knowledge transfer in Natural Language Understanding (NLU), and focus on the neural-based knowledge transfer between languages, which is also known as Cross-Lingual Transfer Learning (CLTL). To facilitate the CLTL of NLU models, especially the CLTL between distant languages, we propose a novel CLTL model named Translation Aided Language Learner (TALL), where CLTL is integrated with Machine Translation (MT). Specifically, we adopt a pre-trained multilingual language model as our baseline model, and construct TALL by appending a decoder to it. On this basis, we directly fine-tune the baseline model as an NLU model to conduct CLTL, but put TALL through an MT-oriented pre-training before its NLU-oriented fine-tuning. To make use of unannotated data, we implement the recently proposed Unsupervised Machine Translation (UMT) technique in the MT-oriented pre-training of TALL. According to the experimental results, the application of UMT enables TALL to consistently achieve better CLTL performance than the baseline model without using more annotated data, and the performance gain is relatively prominent in the case of distant languages
Tributary streams provide migratory fish with access to floodplain habitats in a regulated river: evidence from alligator gar, Atractosteus spatula
No full textMigratory fishes with periodic life history strategies are sensitive to river regulation. Populations of these fishes may persist in highly regulated rivers by using tributaries that provide access to intermittently connected spawning and early life stage habitat in floodplains. We analyzed system hydrology and associated movement of a long-lived periodic strategist, the alligator gar (Atractosteus spatula), in the Brazos River, Texas. We hypothesized that: 1) flow regulation on the mainstem has resulted in the reduction of flood pulses, but tributaries have been less altered; and 2) alligator gar migrate into tributaries during high flows and temperatures. Our analysis revealed that flood pulses were reduced in the mainstem but not in an adjacent, less regulated tributary where floodplain-inundating pulses now outnumber those in the mainstem. Using data from tagged fish, we derived statistical models predicting greater occurrence of alligator gar in tributaries when water temperature exceeded 25° C and mainstem discharge exceeded 400 cms. These results emphasize that movement into less regulated tributaries can mitigate impacts of river regulation on mainstem river populations of alligator gar.The presentation of the authors' names and (or) special characters in the title of the pdf file of the accepted manuscript may differ slightly from what is displayed on the item page. The information in the pdf file of the accepted manuscript reflects the original submission by the author
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