Undefined Structure Research Articles

Pulping black liquor-based polymer hydrogel as water retention material and slow-release fertilizer

Black liquor produced by pulping industry is generally difficult to utilize considering its complex constitutions including lignin with undefined primary structure, various polysaccharides and mineral salts, thus generally being regarded as industrial waste. In this work, we report the preparation of black liquor-based hydrogel (BLH) by a redox free radical induced polymerization process and its applications as both water retention material and slow-release fertilizer. Comparing with the hydrogel prepared without black liquor, the maximum water swelling ratio of the BLH can be enhanced from 69 g/g to 359 g/g, and the water retention ratio was increased from 24.42% to 45.25 %. The hydrogel’s potential application as both water retention material and slow-release fertilizer was verified by performing a cultivating plant test in the hydrogel-mixed sand. Applying this polymer hydrogel as water retention material and slow-release fertilizer achieves the utilization of the whole components of black liquor that were treated as industrial waste before, which not only solve the pollution problem of paper-making process, but also expand its promising application prospect to the afforestation of desertification control projects.

Controllable Self‐Assembly of Peptide‐Cyanine Conjugates In Vivo as Fine‐Tunable Theranostics

AbstractThe fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide‐cyanine conjugates that intracellularly self‐assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase‐3/7 after entering the cells. Then the self‐assembled residue, with a double cyanine substitution (Pr‐2Cy), forms a P helical column in which H‐aggregated cyanine dyes show 3.4‐fold photothermal conversion efficiency compared to free ones. The self‐assembled residue with a single cyanine substitution (Pr‐1Cy) forms a loose column, in which cyanine dyes with undefined structure have a fluorescence quantum yield of up to 9.5 % (emission at 819 nm in H2O). This work provides a simple way to modify in vivo self‐assembled peptides with functional molecules for achieving desired bio‐applications.

Controllable Self-Assembly of Peptide-Cyanine Conjugates In Vivo as Fine-Tunable Theranostics.

The fabrication of functional assemblies with defined structures through controllable molecular packing under physiological conditions is challenging. Here, modularly designed peptide-cyanine conjugates that intracellularly self-assembly into 1D columnar superstructures with controlled cyanine aggregation were designed, and they exhibit distinct imaging or photothermal properties. The peptide backbone is cleaved by caspase-3/7 after entering the cells. Then the self-assembled residue, with a double cyanine substitution (Pr-2Cy), forms a P helical column in which H-aggregated cyanine dyes show 3.4-fold photothermal conversion efficiency compared to free ones. The self-assembled residue with a single cyanine substitution (Pr-1Cy) forms a loose column, in which cyanine dyes with undefined structure have a fluorescence quantum yield of up to 9.5 % (emission at 819 nm in H2 O). This work provides a simple way to modify in vivo self-assembled peptides with functional molecules for achieving desired bio-applications.

Melting Curves of Triolein Polymorphs

AbstractHigh‐pressure treatment is a promising option for improving mechanical properties and processing parameters of fat‐containing products. To identify optimum processing windows, melting curves, crystallization kinetics, and pathways for transferring the optimized structures to atmospheric pressure need to be known. Here, we provide melting curves of different polymorphic forms of triolein in the industrially relevant pressure range. The melting points of different polymorphic forms are detected optically in thin samples during stepwise changes of pressure or temperature. For cross‐nucleated spherulites, this method allows determining the respective melting points of nuclei and overgrown structures. Tracing the melting curves to atmospheric pressure confirms previous identification of the polymorphic forms at high pressure and enables identifying a previously reported but undefined structure as the β2‐form. Employing Raman spectroscopy, it is confirmed that the polymorph remained unaltered during the pressure release. With increasing pressure, the melting curves of the different polymorphic forms approach each other until they successively merge at the highest pressure levels studied.

Endothelial glycocalyx: clinical relevance and translational approach

Endothelial glycocalyx is an undefined structure covering the luminal layer of the vascular endothelium and consisting mainly of three elements: proteoglycans, glycosaminoglycans and glycoproteins. It has different functions, such as the regulation of vascular permeability to liquids and molecules; transduction of the mechanical forces of vascular tension; regulation of coagulation and fibrinolysis cascades; and protection of leukocyte, platelet and pathogen adhesion. The determinants of a glycocalyx lesion can be of several types―e.g., increased tensile forces; reactive oxygen (O ) species; increased plasma level of substances such as sodium (hypernatremia), glucose (hyperglycemia) and cholesterol (hypercholesterolemia); and pro-inflammatory molecules. Any of the above-mentioned noxas, alone or combined, injure the glycocalyx. Its dysfunction will be clinically expressed as endothelial dysfunction, increased vascular permeability, filtration of lipoproteins to the subendothelium, activation of coagulation, or increased adhesion of leukocytes and platelets to the endothelium.

A meta-analysis of catalytic literature data reveals property-performance correlations for the OCM reaction

Decades of catalysis research have created vast amounts of experimental data. Within these data, new insights into property-performance correlations are hidden. However, the incomplete nature and undefined structure of the data has so far prevented comprehensive knowledge extraction. We propose a meta-analysis method that identifies correlations between a catalyst’s physico-chemical properties and its performance in a particular reaction. The method unites literature data with textbook knowledge and statistical tools. Starting from a researcher’s chemical intuition, a hypothesis is formulated and tested against the data for statistical significance. Iterative hypothesis refinement yields simple, robust and interpretable chemical models. The derived insights can guide new fundamental research and the discovery of improved catalysts. We demonstrate and validate the method for the oxidative coupling of methane (OCM). The final model indicates that only well-performing catalysts provide under reaction conditions two independent functionalities, i.e. a thermodynamically stable carbonate and a thermally stable oxide support.

Self‐assembly of a renewable lignin biopolymer in nanoparticles with multiple morphologies

ABSTRACTLignin is considered one of the main biorenewable polymers from natural resources. Each year, a large amount of lignin is generated as a waste byproduct of the pulping process in the paper industry. However, it is seldom treated as a value‐added material because of its undefined structure, the diverse methods of isolation and processing, and the origin of the material; these greatly hinder its application. Therefore, it is of great significance to explore new potential applications of this readily available yet underappreciated natural product. In this study, we developed a preparation method of lignin‐based microstructures or nanostructures via self‐assembly. We created various self‐assembled nanostructures, including nanocubes, nanorods, nano‐octahedrons, nanobranches, and other morphologies, by choosing different types of simple inorganic acids at various pHs. Some of these nanostructures have never been reported. These structures were fully characterized with scanning electron microscopy, ultraviolet–visible spectroscopy, and dynamic light scattering. All of them were uniform and stable. They displayed little or no cytotoxicity to cells in vitro at concentrations up to 1024 μg/mL. We hope the results of this study provide some insight for the future development of new applications of lignin‐based materials. © 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 47482.

Newly Synthesized Lipid-Porphyrin Conjugates: Evaluation of Their Self-Assembling Properties, Their Miscibility with Phospholipids and Their Photodynamic Activity In Vitro.

Lipid-porphyrin conjugates are considered nowadays as promising building blocks for the conception of supramolecular structures with multifunctional properties, required for efficient cancer therapy by photodynamic therapy (PDT). The synthesis of two new lipid-porphyrin conjugates coupling pheophorbide-a (Pheo-a), a photosensitizer derived from chlorophyll-a, to either chemically modified lyso-phosphatidylcholine (PhLPC) or egg lyso-sphingomyelin (PhLSM) is reported. The impact of the lipid backbone of these conjugates on their self-assembling properties, as well as on their physicochemical properties, including interfacial behavior at the air/buffer interface, fluorescence and absorption properties, thermotropic behavior, and incorporation rate in the membrane of liposomes were studied. Finally, their photodynamic activity was evaluated on esophageal squamous cell carcinoma (ESCC) and normal esophageal squamous epithelium cell lines. The liposome-like vesicles resulting from self-assembly of the pure conjugates were unstable and turned into aggregates with undefined structure within few days. However, both lipid-porphyrin conjugates could be efficiently incorporated in lipid vesicles, with higher loading rates than unconjugated Pheo-a. Interestingly, phototoxicity tests of free and liposome-incorporated lipid-porphyrin conjugates demonstrated a better selectivity in vitro to esophageal squamous cell carcinoma relative to normal cells.

Toward Understanding the Mechanism of Calcium-Inhibited Membrane Binding of the SLP-2 C2A Domain

Synaptotagmin-like proteins (Slps) are membrane-binding proteins that play key roles in trafficking of large dense-core vesicles for exocytosis. In particular, Slp-2 is responsible for docking hormone secretory vesicles to sites of exocytosis in pancreatic alpha cells and other cell types. Like all Slp family members, Slp-2 contains an N-terminal Slp-homology domain, a linker region of undefined structure, and two C-terminal membrane-binding C2 domains (C2A and C2B). The C2A domain of Slp-2 has been shown to have a unique response to Ca2+ ions, in that it binds anionic liposome membranes in the absence of Ca2+ but dissociates upon addition of sufficient Ca2+. This Ca2+ dependence contrasts with most other C2 domains, which bind lipid membranes in either a Ca2+-dependent or Ca2+-independent fashion. To investigate the mechanism of this unusual Ca2+ inhibition, a series of biophysical and spectroscopic measurements has been completed. First, the affinity of the well-purified C2A domain for liposomes containing different compositions of key anionic lipids was measured using steady-state and stopped-flow fluorescence spectroscopy. Next, the effect of Ca2+ on C2A domain binding to each of the liposome compositions was measured. It was found that Ca2+ does inhibit membrane binding, albeit at significantly higher concentrations than previously reported. Although the protein-liposome affinity varies by >10-fold among the different lipid compositions tested, the Ca2+ concentration required for inhibition varies relatively little, suggesting a nonspecific mechanism. Current efforts are directed toward quantifying Ca2+ and other metal binding affinities using a luminescence-based Tb3+ displacement assay, and measuring effects of Ca2+ and lipids on protein structure using EPR and NMR.

Collaborative capacity to develop an events portfolio within a small island development state: the Cook Islands

ABSTRACTThis paper develops a framework for understanding and assessing collaborative capacities associated with developing an events portfolio within a small island developing state. The three key features of the collaborative capacity framework are network structure, tie strength and collaborative inertia. We conducted interviews with participants from various government departments, agencies, industry associations, sport organizations, community groups, event organizations and the private sector (e.g. accommodation, transportation, retail and travel agency). Key themes to emerge include calls for an events-focused government agency and a more strategic approach to events, political interference, an undefined network structure, and little or no structural, administrative or institutional links. Collaborative inertia was underpinned by poor private–public sector collaboration, cliques and negative attitudes. Concerns about reliability and competence-based trust were also noted, but corruption was not a great concern. Loss of control, transaction costs, role ambiguity, competition and conflicts of interest also constrained collaborative capacity.

Selective Dispersion of Large‐Diameter Semiconducting Carbon Nanotubes by Functionalized Conjugated Dendritic Oligothiophenes for Use in Printed Thin Film Transistors

AbstractSelective dispersion of semiconducting single walled carbon nanotubes (s‐SWCNTs) by conjugated polymer wrapping is recognized as the most promising scalable method for s‐SWCNT separation. Despite a number of linear conjugated polymers being reported for use in s‐SWCNT separation, these linear polymers suffer batch‐to‐batch variation for their undefined molecular structure. Here, it is reported that conjugated dendritic oligothiophenes with multiple diketopyrrolopyrrole groups at the periphery have the capability of selectively dispersing large diameter s‐SWCNTs with high dispersion efficiency and certain chiral selectivity. Printed top‐gated thin film transistors using the dendrimer sorted s‐SWCNTs show high charge carrier mobility of up to 57 cm2 V−1 s−1 and on/off ratios of ≈106 with high reproducibility, which is ascribed to the defined and monodispersed molecular structure of dendrimers. Moreover, owing to the multiple peripheral anchoring groups of these dendritic molecules, these dendrimer‐s‐SWCNT dispersions display excellent stability. The current work proves that dendritic molecules are excellent dispersion reagents for s‐SWCNT separation.

Genetic Contribution to Degeneration and Repair Potentials of the Intervertebral Disc in Mice

Introduction Intervertebral discs degenerate with age affected by environmental and genetic factors. Presently, there are no direct biological cures as the etiology of disc degeneration is still not well understood. Enchantingly, nearly 10% population are “protected” from intervertebral disc degeneration even above the age of 50. It is most possibly ascribed to genetic causes manipulating disc homeostasis, maintenance or repair mechanism. The LG/J mice possess outstanding healing capability for damages to elastic and articular cartilages, in contrast to the poor healer SM/J mice. Using these parental strains of mice and the recombinant inbreeds, we assessed the potential genetic contributions to degenerative and protective effects on the intervertebral disc. Material and Method: The parental LG/J and SM/J mice together with recombinant inbreeds (RI) LGXSM-6 (80% of LG/J, 20% of SM/J) and LGXSM-33 (50% of LG/J, 50% of SM/J) were studied. Tail discs at P10, 4 weeks and 8weeks of age were assessed with a quantitative histological degeneration scoring system that has been established. The genetic regions common to parental and RIs were assessed with SNP markers for potential degenerative and protective genes, and functional relationship to disc biology assessed using gene ontology and gene network association with the variants from the RI mouse panel. Results In the absence of any environmental perturbation, SM/J mice display early signs of disc degeneration. In contrast, the IVD in LG/J mice remained “healthy” at the same age with vacuolated NP cells, while the nucleus pulposus (NP) in SM/J are degenerative in nature with an undefined NP structure that appear fibrotic. Both LGXSM-6 and LGXSM-33 have even higher degenerative scores than SM/J, suggesting that part of the “protective” loci from LG/J may be absence in these RIs. A more detailed analysis of the overlapping genetic region (less than 20% of the whole genome) contains 178 SNP makers (Herbek et al., 2006) on 87 nearby genes. Unsupervised Gene Ontology analyses identified multiple biology processes enriched in transportation of ions and lipid, channel activity and membrane, cytoskeleton organization, immune response, cell adhesion, migration, cell cycle progression and posttranslational protein modifications for the set of genes. Genes that correlated to immune system and skeletal development included VDR, Ano6, Mttp, Bmpr, and Cep112 informed to be share high associated or have frequent variation. Conclusion LG/J mice have enhanced disc homeostasis and superior healing potential, with a protective effect against disc degeneration. Preliminarily analysis of the gene set (87 genes) suggests changes in the transportation of ions and lipid, and membrane and channel activity may involve in disc function and maintenance. The genomic data can also be used for advanced mapping of the susceptible healing genes identified in articular cartilage repair. It is also promising to map this set of genes across the human whole exome sequencing data that we have generated from 750 individuals for disc degeneration in our population cohort, including elderly with a normal (protect) disc to assess their relevance in our human population study. Acknowledgment This worked is supported by funding from AOSPINE(SRN2012_8), and China's National strategic basic research program(“973”) Grant2014CB942901.

Carbon Materials from Lignin and Sodium Lignosulfonate via Diisocyanate Cross-Linking and Subsequent Carbonization

Applications for lignin and lignosulfonates are limited today due to the undefined structure and varying properties of the substance. However, lignin, as the second most abundant bio-resource besides cellulose and the bio-resource with one of the highest natural carbon contents, has the potential to act as a precursor for carbon materials. In this study we have applied a Kraft lignin and a sodium lignosulfonate with the cross-linker toluene-2,4-diisocyanate. The reaction mixture was molded to form small cylindrical shaped paddings. Cross-linked lignin-polyurethane and lignosulfonate-polyurethane networks were analyzed via elemental analysis and thermogravimetric analysis and finally carbonized. The carbon material was analyzed for its BET surface area and its surface structure via scanning electron microscopy. Surface areas between 70 and 80 m²·g−1 could be reached. Moreover, the material was tested for its adsorption potential of crude oil from water and could take up to twice its own weight. For better understanding of the core chemistry of the cross-linking reaction, we have studied the reaction with model substances to define the reactive groups and the influence of sulfonate groups in the cross-linking reaction of lignin and lignosulfonates with toluene-2,4-diisocyanate.

Prediction of protein folding rates from simplified secondary structure alphabet

Protein folding is a very complicated and highly cooperative dynamic process. However, the folding kinetics is likely to depend more on a few key structural features. Here we find that secondary structures can determine folding rates of only large, multi-state folding proteins and fails to predict those for small, two-state proteins. The importance of secondary structures for protein folding is ordered as: extended β strand>α helix>bend>turn>undefined secondary structure>310 helix>isolated β strand>π helix. Only the first three secondary structures, extended β strand, α helix and bend, can achieve a good correlation with folding rates. This suggests that the rate-limiting step of protein folding would depend upon the formation of regular secondary structures and the buckling of chain. The reduced secondary structure alphabet provides a simplified description for the machine learning applications in protein design.

New Scaffolds for the Delivery of Protease Sensitive Photosensitizer Prodrugs

Photodynamic therapy (PDT) is a non-invasive technique for the treatment of several diseases such as microbial infections, rheumatoid arthritis, age-related macular degeneration, and cancer. However, this therapeutic approach suffers from several drawbacks associated with the administration of conventional photoactive compounds, such as skin photosensitization, unfavorable physicochemical properties, and finally low selectivity for the diseased tissue. To improve the selectivity of conventional photosensitizers (PS) we have developed quenched PS prodrugs based on poly (L) lysine and cyclopeptidic carriers that target up-regulated proteolytic activities related to certain diseases, including cancer. These compounds are based on energy transfer between multiple copies of PSs tethered to oligomeric carriers via protease sensitive peptide linkers, thus, silencing any photodynamic activity. Proteolytic digestion of the peptide results into the release of a PS peptidyl fragment thereby restoring photodynamic activity. These conceptually new compounds act through several complementary targeting mechanisms. They 1) accumulate preferentially in pathologic tissue, 2) target pathology-related proteases, 3) are taken-up selectively by abnormal cells, and 4) being selectively irradiated in the diseased area. Using poly(L)lysine based carriers we have designed quenched PS prodrugs that effectively image and treat prostate cancer. Unfortunately, due to their undefined chemical structure these prodrugs are not suitable for clinical use. Therefore, we have proceeded to design defined quenched PS prodrugs based on a cyclopeptidic carrier vehicle. These novel prodrugs have a constrained secondary structure with a defined molecular weight and predefined number and positions of the PS peptide conjugates. Preliminary evaluation demonstrated that these compounds show the expected tendencies, i.e. increased quenching with increasing number PSs per carrier and digestion by recombinant target proteases including, uPA, Cathepsin B and MMPs. The influence of different design parameters has been investigated in vitro and in vivo. For instance, we have shown that high molecular weight PEGylation is unfavorable for high quenching efficiencies. Furthermore, we have characterized quenched PS prodrugs with respect to activation and phototoxicity in human cancer cell lines with special emphasis on prostate and ovarian cancer. Furthermore, preliminary optimization of pharmacokinetics and biodistribution will be carried out in the chorioallantoic membrane model inoculated with tumor spheroids. Finally, might be possible to translate the gained knowledge into other scientific fields such as for instance the improved drug delivery of chemotherapeutics using cyclopeptidic protease sensitive carriers or the targeted imaging of GLP-1 receptors through the multimerization of targeting moieties onto the cyclopeptidic scaffold.

Activation of Dendritic Cells by the Novel Toll-Like Receptor 3 Agonist RGC100

Toll-like receptor (TLR) 3 agonists emerged as attractive candidates for vaccination strategies against tumors and pathogens. An important mechanism of action of such agonists is based on the activation of TLR3-expressing dendritic cells (DCs), which display a unique capacity to induce and stimulate T-cell responses. In this context, it has been demonstrated that targeting of TLR3 by double-stranded RNA such as poly(I:C) results in potent activation of DCs. Major disadvantages of poly(I:C) comprise its undefined chemical structure and very poor homogeneity, with subsequent unpredictable pharmacokinetics and high toxicity. In the present study, we evaluated the physicochemical properties and biological activity of the novel TLR3 agonist RGC100. RGC100 has a defined chemical structure, with a defined length (100 bp) and molecular weight (64.9 KDa) and a good solubility. RGC100 is stable in serum and activates myeloid DCs through TLR3 targeting, as evidenced by gene silencing experiments. Activation of mouse and human myeloid CD1c+ DCs by RGC100 leads to secretion of several proinflammatory cytokines. In addition, RGC100 improves the ability of CD1c+ DCs to stimulate T-cell proliferation. Due to its physicochemical properties and its immunostimulatory properties, RGC100 may represent a promising adjuvant for prophylactic and therapeutic vaccination strategies.

A novel process for recovery of iron, titanium, and vanadium from titanomagnetite concentrates: NaOH molten salt roasting and water leaching processes

A novel process for recovering iron, titanium, and vanadium from titanomagnetite concentrates has been developed. In the present paper, the treatment of rich titanium–vanadium slag by NaOH molten salt roasting and water leaching processes is investigated. In the NaOH molten salt roasting process, the metallic iron is oxidized into ferriferous oxide, MgTi2O5 is converted to NaCl-type structure of Na2TiO3, and M3O5 (M=Ti, Mg, Fe) is converted to α-NaFeO2-type structure of NaMO2, respectively. Roasting temperature and NaOH–slag mass ratio played a considerable role in the conversion of titanium in the rich titanium–vanadium slag during the NaOH molten salt roasting process. Roasting at 500°C for 60min and a 1:1 NaOH–slag mass ratio produces 96.3% titanium conversion. In the water leaching process, the Na+ was exchanged with H+, Na2TiO3 is converted to undefined structure of H2TiO3, and NaMO2 is converted to α-NaFeO2-type structure of HMO2. Under the optimal conditions, 87.3% of the sodium, 42.3% of the silicon, 43.2% of the aluminum, 22.8% of the manganese, and 96.6% of the vanadium are leached out.

Polymer nanocomposites: structure, interaction, and functionality

This feature article discusses the main factors determining the properties of polymer nanocomposites with special attention paid to structure and interactions. Usually more complicated structure develops in nanocomposites than in traditional particulate filled polymers, and that is especially valid for composites prepared from plate-like nanofillers. Besides the usually assumed exfoliated/intercalated morphology, i.e. individual platelets and tactoids, such nanocomposites often contain large particles, and a network structure developing at large extent of exfoliation. Aggregation and orientation are the most important structural phenomena in nanotube or nanofiber reinforced composites, and ag-gregation is a major problem also in composites prepared with spherical particles. The surface characteristics of nanofillers and interactions are rarely determined or known; the related problems are discussed in the paper in detail. The surface of these reinforcements is modified practically always. The goal of the modification is to improve dispersion and/or adhesion in nanotube and spherical particle reinforced composites, and to help exfoliation in nanocomposites containing platelets. However, modification decreases surface energy often leading to decreased interaction with the matrix. Very limited information exists about interphase formation and the properties of the interphase in nanocomposites, although they must influence properties considerably. The properties of nanocomposites are usually far from the expectations, the main reason being insufficient homogeneity, undefined structure and improper adhesion. In spite of considerable difficulties nanocomposites have great potentials especially in functional applications. Several nanocomposite products are already used in industrial practice demonstrated by a few examples in the article.

Up-scaled equal channel angular pressing of AA6060 and subsequent mechanical properties

Abstract Equal channel angular pressing (ECAP) experiments on AA6060 alloy were performed at room temperature and 150 °C with different pressing speeds. It was possible to accomplish between 3 and 6 passes for the different parameter combinations before cracks were observed at the surface of the billets. The microstructure investigations of the materials revealed a fragmented grain structure and a more undefined mushy structure. Hardness testing showed about 110 Vickers for room temperature and low speed pressings. Tensile testing revealed corresponding results with the highest proof stress of 324 MPa for the same parameter settings. This is typically 75% higher than nominal values for this alloy. Elongation, or ductility, was however lower than nominal values by about 60%.

Functional Nanoscale Organization of Signaling Molecules Downstream of the T Cell Antigen Receptor

Receptor-regulated cellular signaling often is mediated by formation of transient, heterogeneous protein complexes of undefined structure. We used single and two-color photoactivated localization microscopy to study complexes downstream of the T cell antigen receptor (TCR) in single-molecule detail at the plasma membrane of intact T cells. The kinase ZAP-70 distributed completely with the TCRζ chain and both partially mixed with the adaptor LAT in activated cells, thus showing localized activation of LAT by TCR-coupled ZAP-70. In resting and activated cells, LAT primarily resided in nanoscale clusters as small as dimers whose formation depended on protein-protein and protein-lipid interactions. Surprisingly, the adaptor SLP-76 localized to the periphery of LAT clusters. This nanoscale structure depended on polymerized actin and its disruption affected TCR-dependent cell function. These results extend our understanding of the mechanism of T cell activation and the formation and organization of TCR-mediated signaling complexes, findings also relevant to other receptor systems.