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Journal articles on the topic 'Location Affinity'
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1
Brusco, Michael J., and Douglas Steinley. "Affinity Propagation and Uncapacitated Facility Location Problems." Journal of Classification 32, no. 3 (2015): 443–80. http://dx.doi.org/10.1007/s00357-015-9187-x.
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Sandage, Erin. "Create Chapters by Affinity Rather Than Location." Membership Management Report 14, no. 8 (2018): 6. http://dx.doi.org/10.1002/mmr.31011.
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Haja, David, Zoltan Richard Turanyi, and Laszlo Toka. "Location, Proximity, Affinity – The key factors in FaaS." Infocommunications journal, no. 4 (2020): 14–21. http://dx.doi.org/10.36244/icj.2020.4.3.
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The Function-as-a-Service paradigm emerged not only as a pricing technique, but also as a programming model promising to simplify developing to the cloud. Interestingly, while placing functions across hosts under the service platform is believed to be flexible, currently the available platforms pay little attention to co-locate connected functions, or data with the respective processing function in order to improve performance. Even though the local function invocation and data access might be an order of magnitude faster than their remote intra-cloud counterparts. In this paper, we therefore propose a Function-asa- Service platform design that reaps the performance benefits of co-location. We build the platform on WebAssembly, a secure and flexible tool for efficient local function invocations, and on a distributed in-memory database, which allows arbitrary data placement. On top we advocate smart placement strategies for function executions and data, decoupled from the functions. Hence we envision good horizontal scaling of functions while keeping the experienced processing latency to that of a single machine case.
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Hu, Hao, and Liang Zhang. "Social Relationship Analysis and Prediction Based on Location Information." Advanced Materials Research 926-930 (May 2014): 3966–69. http://dx.doi.org/10.4028/www.scientific.net/amr.926-930.3966.
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With the development of smart terminal and smart phones, it is more and more conveniently that obtains the peoples locations and movements trajectory. Even though humans daily movement is free and random, we also can find some regular pattern and periodic movements in daily life. These regular movements and locations make up the daily life pattern. The interactions between two daily life pattern cause person-to-person social relation and effect its changing. So we can describe persons life pattern with location data and we also can describe and infer the relations. In this paper, we propose a new method to quantify and predict social relationship affinity with absolute location and approximation location data.
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Chen, X. H., L. Niu, Y. J. Zhou, Z. Bi, G. Ding, and D. Liang. "Rss-based Affinity Propagation Algorithm Accuracy Improvement Considering Physical Location." Information Technology Journal 12, no. 18 (2013): 4544–48. http://dx.doi.org/10.3923/itj.2013.4544.4548.
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Dr., Ravi Shankar Pandey, and Pathak Richa. "AN ADAPTIVE APPROACH FOR DYNAMIC RECOVERY DECISIONS IN WEB SERVICE COMPOSITION USING SPACE BASED QOS FACTOR." International Journal on Web Service Computing (IJWSC) 6, no. 2/3 (2015): 11–26. https://doi.org/10.5281/zenodo.3706486.
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Service Oriented Architecture facilitates automatic execution and composition of web services in distributed environment. This service composition in the heterogeneous environment may suffer from various kinds of service failures. These failures interrupt the execution of composite web services and lead towards complete system failure. The dynamic recovery decisions of the failed services are dependent on non-functional attributes of the services. In the recent years, various methodologies have been presented to provide recovery decisions based on time related QoS (Quality of Service) factors. These QoS attributes can be categorized further. Our paper categorized these attributes as space and time. In this paper, we have proposed an affinity model to quantify the location affinity for composition of web services. Furthermore, we have also suggested a replication mechanism and algorithm for taking recovery decisions based on time and space based QoS parameters and usage pattern of the services by the user.
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Zhang, Yajun, Jie Deng, Kangkang Zhu, Yongqiang Tao, Xiaolin Liu, and Ligang Cui. "Location and Expansion of Electric Bus Charging Stations Based on Gridded Affinity Propagation Clustering and a Sequential Expansion Rule." Sustainability 13, no. 16 (2021): 8957. http://dx.doi.org/10.3390/su13168957.
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With the escalating contradiction between the growing demand for electric buses and limited supporting resources of cities to deploy electric charging infrastructure, it is a great challenge for decision-makers to synthetically plan the location and decide on the expansion sequence of electric charging stations. In light of the location decisions of electric charging stations having long-term impacts on the deployment of electric buses and the layout of city traffic networks, a comprehensive framework for planning the locations and deciding on the expansion of electric bus charging stations should be developed simultaneously. In practice, construction or renovation of a new charging station is limited by various factors, such as land resources, capital investment, and power grid load. Thus, it is necessary to develop an evaluation structure that combines these factors to provide integrated decision support for the location of bus charging stations. Under this background, this paper develops a gridded affinity propagation (AP) clustering algorithm that combines the superiorities of the AP clustering algorithm and the map gridding rule to find the optimal candidate locations for electric bus charging stations by considering multiple impacting factors such as land cost, traffic conditions, and so on. Based on the location results of the candidate stations, the expansion sequence of these candidate stations is proposed. In particular, a sequential expansion rule for planning the charging stations is proposed that considers the development trends of the charging demand. To verify the performance of the gridded AP clustering and the effectiveness of the proposed sequential expansion rule, an empirical investigation of Guiyang City, the capital of Guizhou province in China, is conducted. The results of the empirical investigation demonstrate that the proposed framework that helps find optimal locations for electric bus charging stations and the expansion sequence of these locations are decided with less capital investment pressure. This research shows that the combination of gridded AP clustering and the proposed sequential expansion rule can systematically solve the problem of finding the optimal locations and deciding on the best expansion sequence for electric bus charging stations, which denotes that the proposed structure is pretty pragmatic and would benefit the government for long-term investment in electric bus station deployment.
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VOROTNIKOV, V. Alexander, B. Steven MARSTON, and A. J. Pia HUBER. "Location and functional characterization of myosin contact sites in smooth- muscle caldesmon." Biochemical Journal 328, no. 1 (1997): 211–18. http://dx.doi.org/10.1042/bj3280211.
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Caldesmon interaction with smooth muscle myosin and its ability to cross-link actin filaments to myosin were investigated by the use of several bacterially expressed myosin-binding fragments of caldesmon. We have confirmed the presence of two functionally different myosin-binding sites located in domains 1 and 3/4a of caldesmon. The binding of the C-terminal site is highly sensitive to ionic strength and hardly participates in acto-myosin cross-linking, while the N-terminal binding site is relatively independent of ionic strength and apparently contains two separate myosin contact regions within residues 1-28 and 29-128 of chicken gizzard caldesmon. Both these N-terminal sub-sites are involved in the interaction with myosin and are predominantly responsible for the caldesmon-mediated high-affinity cross-linking of actin and myosin filaments, without affecting the affinity of direct acto-myosin interaction. Binding of caldesmon and its fragments to myosin or rod filaments revealed affinity in the micromolar range. We determined various stoichiometries at maximal binding, which depended on the ionic strength and the concentration of Mg2+ ions. At 30 mM NaCl and 1 mM Mg2+ the maximum stoichiometry was 4 moles of caldesmon (or caldesmon fragment) per mole of myosin. At 130 mM NaCl/1 mM Mg2+, or at 30 mM NaCl/5 mM Mg2+ it decreased to about two caldesmon molecules bound per myosin, while remaining 4:1 for individual caldesmon fragments, suggesting that all binding sequences on myosin were still fully capable of interaction. A further increase in the Mg2+ concentration led to a substantial decrease in both the affinity and maximum stoichiometry of caldesmon and the fragments binding to myosin. We suggest that caldesmon-myosin interaction varies according to the conformation of caldesmon in solution, that caldesmon-binding sites on myosin are not well defined and that their accessibility is determined by spatial organization and is blocked by divalent cations like Mg2+.
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Jacobsson, K. G., U. Lindahl, and A. A. Horner. "Location of antithrombin-binding regions in rat skin heparin proteoglycans." Biochemical Journal 240, no. 3 (1986): 625–32. http://dx.doi.org/10.1042/bj2400625.
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Rat skin heparin proteoglycan labelled biosynthetically with 35S was fractionated on a column of antithrombin-Sepharose into fractions with varying degrees of affinity for antithrombin. These were treated with NaOH to release heparin chains (Mr 60,000-100,000), by beta-elimination or incubated with serum to produce fragments of the same order of size as commercial heparin (Mr 5000-30,000), by endoglycosidase cleavage. Chains and fragments were then fractionated on antithrombin-Sepharose. The various fractions were deaminated with HNO2 at pH 1.5 followed by reduction with NaB3H4. Approx 90% of the incorporated 3H was associated with disaccharides. These were fractionated by high-performance ion-exchange chromatography. A unique minor component corresponding to the sequence glucuronosyl-N-sulphoglucosaminyl (3,6-di-O-sulphate) in the polysaccharide was found only in fractions with high affinity for antithrombin. The glucosamine residue linked to C-4 of this glucuronosyl unit was predominantly (or exclusively) N-sulphated rather than N-acetylated, pointing to a structural difference between the antithrombin-binding region of rat heparin and that of pig mucosal heparin. Calculations based on the distribution of the glucosaminyl 3-O-sulphate group showed that approximately two-thirds of the total antithrombin-binding regions present in the unfractionated material were accommodated by only 20% of the proteoglycan molecules, and by 10% of the polysaccharide chains. While most of the proteoglycan molecules thus lacked such regions (and hence affinity for antithrombin) a minor proportion of the polysaccharide chains contained on the average three binding regions per molecule. These findings support by direct chemical analysis an earlier proposal, based on anticoagulant activities of similar rat skin heparin fractions, that the distribution of antithrombin-binding sites in intact heparin proteoglycans is markedly non-random.
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Dan, Ovidiu, Vaibhav Parikh, and Brian D. Davison. "IP Geolocation through Geographic Clicks." ACM Transactions on Spatial Algorithms and Systems 8, no. 1 (2022): 1–22. http://dx.doi.org/10.1145/3476774.
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IP geolocation databases map IP addresses to their physical locations. They are used to determine the location of online users when their precise location is unavailable. These databases are vital for a number of online services, including search engine personalization, content delivery, local ads, and fraud detection. However, IP geolocation databases are often inaccurate. In this work we present two novel approaches to improving IP geolocation by mining search engine click logs. First, we show that we can derive which URLs have local affinity by clustering clicks from IPs with known locations. We demonstrate that we can further propagate these URL locations to IP addresses with unknown locations. Our approach significantly outperforms two state-of-the-art commercial IP geolocation databases by 25 and 36 percentage points at a distance error of 10 kilometers, respectively. Second, we present an alternative method of assigning locations to URLs when IP location training data is not available, by instead extracting locations from the body of web documents. This second approach also outperforms the baselines by 7 and 17 percentage points, respectively, and has higher coverage than the first method. Finally, we also demonstrate that our two approaches outperform the academic state of the art based on mining query logs.
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Wang, Chao Ying, and Zhi Neng Liu. "An Immunity-Based Algorithm for Distribution Center Location." Advanced Materials Research 971-973 (June 2014): 1537–42. http://dx.doi.org/10.4028/www.scientific.net/amr.971-973.1537.
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The distribution center is the bridge connected supply points and demand points, lies in pivotal status in modern logistics system. Firstly, the mathematical model of a distribution center location is established, based on the study of using neural network to solve distribution center location of the previous scholars, a new method is presented as well as the improved immune algorithm. A new affinity formula is designed for immunoselection criteria. Simultaneously, based on the mathematical model and cases, the algorithm is drilled concrete. A case shows that the improved immune algorithm can better solve the problem of the distribution center location.
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Asada, Mizue, and Hiroyuki Mino. "Location of the High-Affinity Mn2+ Site in Photosystem II Detected by PELDOR." Journal of Physical Chemistry B 119, no. 32 (2015): 10139–44. http://dx.doi.org/10.1021/acs.jpcb.5b03994.
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Koni, Pandelakis A., and Richard A. Flavell. "Lymph Node Germinal Centers Form in the Absence of Follicular Dendritic Cell Networks." Journal of Experimental Medicine 189, no. 5 (1999): 855–64. http://dx.doi.org/10.1084/jem.189.5.855.
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Follicular dendritic cell networks are said to be pivotal to both the formation of germinal centers (GCs) and their functions in generating antigen-specific antibody affinity maturation and B cell memory. We report that lymphotoxin β–deficient mice form GC cell clusters in the gross anatomical location expected of GCs, despite the complete absence of follicular dendritic cell networks. Furthermore, antigen-specific GC generation was at first relatively normal, but these GCs then rapidly regressed and GC-phase antibody affinity maturation was reduced. Lymphotoxin β–deficient mice also showed substantial B cell memory in their mesenteric lymph nodes. This memory antibody response was of relatively low affinity for antigen at week 4 after challenge, but by week 10 after challenge was comparable to wild-type, indicating that affinity maturation had failed in the GC phase but developed later.
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Zimmerman, Christopher, Kjeld Hansen, and Ravi Vatrapu. "A Theoretical Model for Digital Reverberations of City Spaces and Public Places." International Journal of Electronic Government Research 10, no. 1 (2014): 46–62. http://dx.doi.org/10.4018/ijegr.2014010104.
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The increasing pervasiveness of Internet connected devices and services is altering the perception and practice of public spaces through the provisioning of location-specific digital information. Location-aware technologies allow people to access, annotate, address and attach information to locations, which transforms the space for other people who use the same services. Such locations acquire relevance and reshape social and spatial interactions through increased use on social media as people ‘check-in' to places, photograph or ‘like' them. Collectively the authors are marking-up the city around them. The popularization of location-aware technologies thus contributes to the changing meaning of locations in cities. In contrast to the technological focus in the emerging discourses on smart cities and big data, this paper offers an alternative view of the three lenses of Social, Local and Mobile technologies that describe and explain crowd-sourced socio-technical layers on the city landscape. The proposed integrated theoretical model describes the relevant information linkages between people and places in the online and offline worlds and introduces a new evaluation method for the evaluation of city places: affinity spectrum of social endorsements. The authors conclude with a discussion of the new opportunities for governments to better understand socially emergent ‘urban qualities' and how citizens construct and appreciate them in order better convert city places into public spaces.
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Guo-ying, Zhou, Guo Liang, Li Lin, and Li He. "rDNA internal transcribed spacer sequence analysis of Craterellus tubaeformis from North America and Europe." Canadian Journal of Microbiology 57, no. 1 (2011): 29–32. http://dx.doi.org/10.1139/w10-098.
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The basidiomycete Craterellus tubaeformis (Fries) Quélet is an important widespread ectomycorrhizal basidiomycete found in the Northern Hemisphere. In this study, 12 samples of C. tubaeformis from North America and Europe were analyzed using internal transcribed spacer (ITS) sequences to reveal the correlation between ITS genotypes and geographic locations and to provide molecular evidence for the identification of C. tubaeformis from different habitats in North America and Europe. The analyses identified abundant sequence variations within C. tubaeformis. The length of the ITS region varied from 571 to 640 bp. The proportion of variable sites was 17.6%, and the proportion of parsimony information sites was 16.7%. Phylogenetic analysis showed some correlations between the ITS genotypes and geographic locations of C. tubaeformis; however, some discrepancies between geographical location and affinity were also found. The results indicated that C. tubaeformis from different habitats in North America and Europe underwent genetic drifting and evolved into 2 different species. nrDNA ITS could be a good markers for distinguishing among C. tubaeformis from different habitats, but rational affinity should be determined by associating the available ITS data with other information sources.
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Summers, R. J., J. A. Stephenson, S. Lipe та C. B. Neylon. "α2-Adrenoceptors in dog kidney: autoradiographic localization and putative functions". Clinical Science 68, s10 (1985): 105s—109s. http://dx.doi.org/10.1042/cs068s105.
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1. The location of α2-adrenoceptors has been examined in slide-mounted sections of dog kidney by using labelling in vitro with [3H]rauwolscine and autoradiography. 2. [3H]Rauwolscine binding in dog kidney was of high affinity, saturable, and to a single population of sites. Stereoselectivity was observed for (−)-noradrenaline and the relative affinity of a series of competing antagonists indicated binding to α2-adrenoceptors. 3. Autoradiography of [3H]rauwolscine binding revealed localization to three areas: glomeruli, the intimal and adventitial surfaces of arcuate blood vessels and the medullary vascular bundles.
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Fiedor, Joanna, Mateusz Przetocki, Aleksander Siniarski та ін. "β-Carotene-Induced Alterations in Haemoglobin Affinity to O2". Antioxidants 10, № 3 (2021): 451. http://dx.doi.org/10.3390/antiox10030451.
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β-Carotene (β-Crt) can be dispersed in hydrophobic regions of the membrane of red blood cells (RBC). Its location, orientation and distribution strongly depend on carotenoid concentration. In the present pilot trial (six human subjects involved), it is demonstrated that incubation of RBCs with β-Crt (1.8 × 107 β-Crt molecules per RBC, 50 μmol/L) results in expansion of the membrane of RBCs and slight elongation of the cell. The changes are of statistical significance, as verified by the Wilcoxon test at p < 0.05. They indicate (i) a highly random orientation and location of β-Crt inside the membrane and (ii) a tendency for its interaction with membrane skeleton proteins. The accompanying effect of decreased RBC resistance to lysis is possibly a result of the incorrect functioning of ion channels due to their modification/disruption. At higher β-Crt concentrations, its clustering inside membranes may occur, leading to further alterations in the shape and size of RBCs, with the most pronounced changes observed at 1.8 × 108 β-Crt molecules per RBC (500 μmol/L). Due to the reduced permeability of ions, such membranes exhibit increased resistance to haemolysis. Finally, we show that interactions of β-Crt with the membrane of RBCs lead to an alteration in haemoglobin-oxygen affinity, shifting the oxyhaemoglobin dissociation curve toward higher oxygen partial pressures. If the impact of β-Crt on a curve course is confirmed in vivo, one may consider its role in the fine tuning of O2 transportation to tissues. Hence, at low concentrations, providing unchanged elastic and functional properties of RBCs, it could serve as a beneficial agent in optimising heart performance and cardiovascular load.
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Stoler-Barak, Liat, Adi Biram, Natalia Davidzohn, Yoseph Addadi, Ofra Golani, and Ziv Shulman. "B cell dissemination patterns during the germinal center reaction revealed by whole-organ imaging." Journal of Experimental Medicine 216, no. 11 (2019): 2515–30. http://dx.doi.org/10.1084/jem.20190789.
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Germinal centers (GCs) are sites wherein B cells proliferate and mutate their immunoglobulins in the dark zone (DZ), followed by affinity-based selection in the light zone (LZ). Here, we mapped the location of single B cells in the context of intact lymph nodes (LNs) throughout the GC response, and examined the role of BCR affinity in dictating their position. Imaging of entire GC structures and proximal single cells by light-sheet fluorescence microscopy revealed that individual B cells that previously expressed AID are located within the LN cortex, in an area close to the GC LZ. Using in situ photoactivation, we demonstrated that B cells migrate from the LZ toward the GC outskirts, while DZ B cells are confined to the GC. B cells expressing very-low-affinity BCRs formed GCs but were unable to efficiently disperse within the follicles. Our findings reveal that BCR affinity regulates B cell positioning during the GC response.
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Nováková, Barbora Marie. "The Impact of Regional and Segmental Factors on the Benefits and Risks of Venture Capital Financing." Journal of Economics, Finance and Accounting Studies 6, no. 1 (2024): 78–84. http://dx.doi.org/10.32996/jefas.2024.6.1.8.
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This paper presents an analysis of aspects of venture capital (VC) financing, focusing on risks and rewards, correlation with geographic location and industry. The results were obtained through statistical analysis of data from public startup databases and a questionnaire distributed to selected VC-funded startups. The aim of the paper was to analyze the risks and benefits of VC funding and the impact of regional and segment factors. The paper identifies the key benefits of VC funding as fast and flexible access to capital, while the key risks include loss of control over the business and high pressure on performance. The analysis suggests that the perceived riskiness of VC financing is strongly influenced by both geographic location and industry. Certain geographic locations were found to have an affinity for specific industries, suggesting regional specialization within the VC market. The paper reveals significant trends in funding, with the dominance of technology startups, business platforms and the HealthTech sector, and increasing activity in certain regions in recent years.
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Thompson, Jill, and Ted Begenisich. "Affinity and Location of an Internal K+ Ion Binding Site in Shaker K Channels." Journal of General Physiology 117, no. 5 (2001): 373–84. http://dx.doi.org/10.1085/jgp.117.5.373.
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We have examined the interaction between TEA and K+ ions in the pore of Shaker potassium channels. We found that the ability of external TEA to antagonize block of Shaker channels by internal TEA depended on internal K+ ions. In contrast, this antagonism was independent of external K+ concentrations between 0.2 and 40 mM. The external TEA antagonism of internal TEA block increased linearly with the concentration of internal K+ ions. In addition, block by external TEA was significantly enhanced by increases in the internal K+ concentration. These results suggested that external TEA ions do not directly antagonize internal TEA, but rather promote increased occupancy of an internal K+ site by inhibiting the emptying of that site to the external side of the pore. We found this mechanism to be quantitatively consistent with the results and revealed an intrinsic affinity of the site for K+ ions near 65 mM located ∼7% into the membrane electric field from the internal end of the pore. We also found that the voltage dependence of block by internal TEA was influenced by internal K+ ions. The TEA site (at 0 internal K+) appeared to sense ∼5% of the field from the internal end of the pore (essentially colocalized with the internal K+ site). These results lead to a refined picture of the number and location of ion binding sites at the inner end of the pore in Shaker K channels.
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Hou, Feng. "Changes in the Initial Destinations and Redistribution of Canada's Major Immigrant Groups: Reexamining the Role of Group Affinity." International Migration Review 41, no. 3 (2007): 680–705. http://dx.doi.org/10.1111/j.1747-7379.2007.00090.x.
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This study examines to what extent Canada's recent immigrants have altered their geographic concentration over time, with a view of determining the role of preexisting immigrant communities in immigrants' locational choices, looking specifically at community size. The results show a large increase in concentration levels at the initial destination among major immigrant groups throughout the 1970s and 1980s, and a much smaller increase in the following decade. However, redistribution after immigration was generally small-scale and had inconsistent effects on changing concentration at initial destinations among immigrant groups and across arrival cohorts within an immigrant group. Finally, this study finds that the size of the preexisting immigrant community is not a significant factor in immigrant locational choice when location fixed effects are accounted for.
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Cohen-Khait, Ruth, and Gideon Schreiber. "Low-stringency selection of TEM1 for BLIP shows interface plasticity and selection for faster binders." Proceedings of the National Academy of Sciences 113, no. 52 (2016): 14982–87. http://dx.doi.org/10.1073/pnas.1613122113.
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Protein–protein interactions occur via well-defined interfaces on the protein surface. Whereas the location of homologous interfaces is conserved, their composition varies, suggesting that multiple solutions may support high-affinity binding. In this study, we examined the plasticity of the interface of TEM1 β-lactamase with its protein inhibitor BLIP by low-stringency selection of a random TEM1 library using yeast surface display. Our results show that most interfacial residues could be mutated without a loss in binding affinity, protein stability, or enzymatic activity, suggesting plasticity in the interface composition supporting high-affinity binding. Interestingly, many of the selected mutations promoted faster association. Further selection for faster binders was achieved by drastically decreasing the library–ligand incubation time to 30 s. Preequilibrium selection as suggested here is a novel methodology for specifically selecting faster-associating protein complexes.
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Priyanka S, Harshita S.S, Geethamani P.R, Pooja M, Brinda.L, and Manohar G M. "Higher binding affinity in mutant G614 SARS-CoV2 may explain the higher prevalence of Anosmia in European countries." international journal of engineering technology and management sciences 7, no. 3 (2023): 825–31. http://dx.doi.org/10.46647/ijetms.2023.v07i03.127.
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Anosmia is a condition where there is a loss of smell in people affected by covid 19. The prevalence of anosmia differs according to the geographical location. The prevalence of chemosensory dysfunction in Europeans was found to be three times higher than that in Asians. We observed that these geographical locations are also characterised by the occurrence of unique mutant strains G614 found in European countries and D614 wild-type strain of the SARS-CoV2 in Asian countries. Assuming that there may be a correlation between the mutation and the infection efficiency that in turn might affect the anosmia prevalence we analysed the binding affinity (with its receptor ACE2) and other features of the mutation. Using FoldX we built a mutant model G614 and found that the stability of the protein is not much affected. However, the difference in interaction energy with the receptor ACE2 showed a difference of around 10 kcal/mol. FoldX analyze complex analysis showed that the interaction energy is stronger in mutant strain hence high binding affinity. Pymol visualisation showed that the mutation was on the surface of the Spike protein. A phylogenetic tree of available ACE2 human sequences showed that Anosmia prevalence is not correlated with the variation in ACE2 sequences of different ethnic/geographical samples. Our study finds that the binding affinity of the mutant strain is high and therefore a possibility of explaining the correlation observed with the mutant strain and prevalence of anosmia.
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Brandic, Ivona, Sabri Pllana, and Siegfried Benkner. "An Approach for the High-Level Specification of QoS-Aware Grid Workflows Considering Location Affinity." Scientific Programming 14, no. 3-4 (2006): 231–50. http://dx.doi.org/10.1155/2006/670375.
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Many important scientific and engineering problems may be solved by combining multiple applications in the form of a Grid workflow. We consider that for the wide acceptance of Grid technology it is important that the user has the possibility to express requirements on Quality of Service (QoS) at workflow specification time. However, most of the existing workflow languages lack constructs for QoS specification. In this paper we present an approach for high level workflow specification that considers a comprehensive set of QoS requirements. Besides performance related QoS, it includes economical, legal and security aspects. For instance, for security or legal reasons the user may express the location affinity regarding Grid resources on which certain workflow tasks may be executed. Our QoS-aware workflow system provides support for the whole workflow life cycle from specification to execution. Workflow is specified graphically, in an intuitive manner, based on a standard visual modeling language. A set of QoS-aware service-oriented components is provided for workflow planning to support automatic constraint-based service negotiation and workflow optimization. For reducing the complexity of workflow planning, we introduce a QoS-aware workflow reduction technique. We illustrate our approach with a real-world workflow for maxillo facial surgery simulation.
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Reed, R. G. "Location of long chain fatty acid-binding sites of bovine serum albumin by affinity labeling." Journal of Biological Chemistry 261, no. 33 (1986): 15619–24. http://dx.doi.org/10.1016/s0021-9258(18)66760-2.
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Hayat, Tanzim, ASM Maksud Kamal, Md Shakhawat Hossain, Saiyeba Zaman, BM Rabby Hossain, and Tapas Ranjan Chakraborty. "Accessibility Analysis of Cyclone Shelters - A Case Study for Atulia Union, Satkhira, Bangladesh." Journal of the Asiatic Society of Bangladesh, Science 46, no. 2 (2021): 163–78. http://dx.doi.org/10.3329/jasbs.v46i2.54412.
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Cyclone shelters are considered as a solution to reduce cyclone risk in coastal districts of Bangladesh. The location of a shelter plays a crucial part in a potential user’s decisionmaking process. If the perception is that the shelter is too far away, the user may decide not to use it. On the other hand, it would not be financially feasible to construct shelters near every settlement cluster. Therefore, network analysis using GIS has been applied to reveal the optimal location. Apart from distance, there are some other factors (like space, presence of gender segregated rooms and toilets, ramped access way, availability of drinking water, etc.), which affect a user’s affinity to evacuate to a specific shelter. All the shelters in Atulia Union from Satkhira District of Bangladesh were visited to identify these characteristics. Finally, an index was developed to determine the preference of each shelter to its potential users. It was found that there is inadequate number of shelters in the study area and two new shelter locations were recommended.
 Asiat. Soc. Bangladesh, Sci. 46(2): 163-178, December 2020
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JARJAPU, MAHITA, CoVIC-DB TEAM, ERICA OLLMANN SAPHIRE, and BJOERN PETERS. "Large-scale analysis of CoVIC antibodies by a global consortium identifies predictors of in vivoprotection." Journal of Immunology 210, no. 1_Supplement (2023): 146.11. http://dx.doi.org/10.4049/jimmunol.210.supp.146.11.
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Abstract The Coronavirus Immunotherapeutic Consortium (CoVIC) was established to develop prevention and therapeutic strategies against SARS-CoV-2 that could be used in low- and middle-income countries. The CoVIC compiled a unique panel comprising nearly 400 candidate therapeutic antibodies contributed by 60 groups in industry, academic, and government settings. All antibodies in the CoVIC panel were first blinded at the CoVIC headquarters at the La Jolla Institute for Immunology through the assignment of a code name. Identical sets of antibodies were then sent under the assigned code names to seven different partner reference labs that carried out side-by-side, standardized analyses of binding affinity, epitope location, high resolution structures, pseudovirus and authentic virus neutralization, in vivo protection, and Fc-mediated effector functions. The reference labs deposited their data, which was then validated and made publicly accessible, in the CoVIC database (CoVIC-DB). Using various statistical analyses of the data, we investigated relationships among functional properties of the antibodies. For example, we could discern that binding affinity to the full-length spike is more predictive of neutralization potency than binding affinity to the RBD, and that binding affinity and epitope location together correlates with neutralization. However, neutralization alone is not sufficient to explain in vivo protection in the K18 mouse model of SARS-CoV-2 infection, as other factors such as antibody pharmacokinetics were also important. Overall, the results of this study revealed important insights into antibody properties that are good predictors of in vivo protection by CoVIC antibodies. COVIC-19 Therapeutics Accelerator (a partnership of Bill and Melinda Gates Foundation), Bill and Melinda Gates Foundation, Mastercard, Wellcome Trust, National Institute of Allergy and Infectious Diseases of the National Institutes of Health, GHR Foundation, FastGrant from Emergent Ventures
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Stevens, F. J., J. Jwo, W. Carperos, H. Köhler, and M. Schiffer. "Relationships between liquid- and solid-phase antibody association characteristics: implications for the use of competitive ELISA techniques to map the spatial location of idiotopes." Journal of Immunology 137, no. 6 (1986): 1937–44. http://dx.doi.org/10.4049/jimmunol.137.6.1937.
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Abstract A liquid-phase assay system based on small-zone size-exclusion chromatography was used to examine the binding of a monoclonal anti-idiotopic antibody, F6, to its idiotope on the murine plasmacytoma IgA, TEPC-15. Chromatographic behavior revealed a strong association between T-15 and F6, which was previously characterized by solid-phase immunoassay as recognizing a nonbinding site epitope of the T-15. This chromatographic pattern suggests that the inability of the hapten phosphorylcholine to inhibit the anti-idiotope:idiotope relationship in solid-phase immunoassay might be equally explained by the low affinity of the hapten relative to the high affinity of the anti-idiotope antibody. Bivalent interactions between solid-phase IgA and liquid-phase IgG should enhance the binding of the anti-idiotope to an extent that would prevent the hapten from dissociating the complex. Under these solid-phase assay conditions, observation of hapten inhibition may, in some cases, indicate site specificity, but absence of inhibition cannot be interpreted. Computer simulations of solid-phase hapten inhibition scenarios were used to evaluate the qualitative nature of binding inhibition profiles expected under various conditions of liquid- and solid-phase reactant affinities and concentrations. The apparently unusual inhibition curves previously observed in the T-15:anti-T-15 studies in which the degree of binding inhibition by hapten appeared to be independent of anti-idiotope concentration may be predictable in cases of excess solid-phase epitope; the plateau inhibition value is a function of relative affinity constants and concentrations of solid-phase and inhibitor components. The results additionally suggest that the affinity of a liquid-phase antibody may modulate the effective concentration of solid-phase epitope.
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Huber, P. A. J., I. D. C. Fraser, and S. B. Marston. "Location of smooth-muscle myosin and tropomyosin binding sites in the C-terminal 288 residues of human caldesmon." Biochemical Journal 312, no. 2 (1995): 617–25. http://dx.doi.org/10.1042/bj3120617.
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We have produced nine recombinant fragments, H1 to H9, from a human cDNA that codes for the C-terminal 288 residues of caldesmon. The fragment H1, encompassing the 288 residues, is equivalent to domains 3 and 4 of caldesmon (amino acids 506-793 in human, 476-737 in the chicken gizzard sequence). It has been shown [Huber, Redwood, Avent, Tanner and Marston (1993) J. Muscle Res. Cell Motil. 14, 385-391] to bind to actin, Ca(2+)-calmodulin, tropomyosin and myosin. The fragments, H2 to H9, differ in length between 60 and 176 residues and cover the whole of domains 3 and 4 with many of the fragments overlapping. We have characterized the myosin and tropomyosin binding of these fragments. The binding of both tropomyosin and myosin is highly dependent on salt concentration, indicating the ionic nature of these interactions. The location of the myosin binding is an extended region encompassing the junction of domains 3/4 and domain 4a (residues 622-714, human; 566-657, chicken gizzard). Tropomyosin binds in a smaller region within domain 4a of caldesmon (residues 663-714, human; 606-657 chicken gizzard). We confirmed predictions based on sequence similarities of a tropomyosin binding site in domain 3 of caldesmon; however, this site bound to skeletal-muscle tropomyosin and had little affinity for the smooth-muscle tropomyosin isoform. None of the protein fragments H2-H9 retained the affinity of the parent fragment H1 for either myosin or tropomyosin. This indicates the need for several interaction sites scattered over an extended region to attain higher affinity. The regions interacting with caldesmon in both tropomyosin and myosin are coiled-coil structures. This is probably the reason for their shared interaction sites on caldesmon and their similar natures of binding.
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Wold, J. K., H. S. Slayter, J. F. Codington, and R. W. Jeanloz. "Location of an epitopic site on epiglycanin by molecular immunoelectron microscopy." Biochemical Journal 227, no. 1 (1985): 231–37. http://dx.doi.org/10.1042/bj2270231.
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Antibodies of the IgM type present in rabbit anti-epiglycanin antiserum were purified by (NH4)2SO4 precipitation and by ion-exchange, affinity and gel-filtration chromatography. After papain treatment of this fraction, followed by gel filtration, the fraction with highest apparent Mr was incubated with epiglycanin, and the antigen-antibody complexes separated by gel filtration. These were examined by electron microscopy, using rotational shadow casting, and the photographs of the complexes were mapped for the locations of the antibody molecules on the extended epiglycanin molecules. Distribution of the frequency of attachment of immunoglobulin showed a strong tendency toward binding at one end of epiglycanin, suggesting the probable presence of only one epitope, probably a glycopeptide structure containing a beta-D-galactopyranosyl-(1→3)-2-acetamido-2-deoxy-D-galactose chain.
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Kragh-Hansen, U. "Octanoate binding to the indole- and benzodiazepine-binding region of human serum albumin." Biochemical Journal 273, no. 3 (1991): 641–44. http://dx.doi.org/10.1042/bj2730641.
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Binding of L-tryptophan, diazepam and octanoate to defatted human serum albumin was studied at pH 7.0 by equilibrium dialysis at low ligand/protein molar ratios. L-Tryptophan binding takes place at only one site of the protein with an association constant of 4.4 x 10(4) M-1. Under the present experimental conditions, binding of diazepam and octanoate could be accounted for by high-affinity binding alone with primary association constants of 3.8 x 10(5) M-1 and 1.6 x 10(6) M-1 respectively. During the simultaneous presence of L-tryptophan plus octanoate or diazepam plus octanoate, pronounced mutual reductions in binding were observed. Analysis of the data suggests that the reductions in binding represent competition for a common high-affinity binding site. Thus a region seems to exist that is capable of binding one molecule of these diverse ligands with a high affinity. The location of this region within the albumin molecule is discussed.
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Razani, Nooshin, Nancy K. Hills, Doug Thompson, and George W. Rutherford. "The Association of Knowledge, Attitudes and Access with Park Use before and after a Park-Prescription Intervention for Low-Income Families in the U.S." International Journal of Environmental Research and Public Health 17, no. 3 (2020): 701. http://dx.doi.org/10.3390/ijerph17030701.
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We conducted secondary data analyses of pooled data from a clinical trial that prescribed park visits to children and their caregivers in a low-income, urban setting. Data were collected at the prescribing visit (baseline) and at one and three months of follow up from 78 families. Family characteristics were identified at baseline; regression models were used to explore changes during follow up in associations of park use with knowledge, attitudes and perceived access to parks. At baseline, park users differed from non-users in demographics, knowledge of park locations, attitudes about the value of park visits, but not affinity for nature. Park users were also more likely than non-users to feel that their neighborhood was safe for children to play in. Changes in knowledge of park locations, nature affinity, and perceived access to parks were each significantly associated with increased park use by families at one and three months after the park prescription. Adjusting for age, gender, race, poverty, and US birth, increases in knowing the location of parks were associated with an increase of 0.27 weekly park visits (95% CI 0.05, 0.49; p = 0.016); increases in feeling a caregiver had money to visit parks were associated with 0.48 more weekly park visits (95% CI 0.28, 0.69; p < 0.001); increases in perceived money for park outings were associated with 0.24 increased park visits per week (95% CI 0.05, 0.42; p = 0.01); each unit increase in nature affinity was associated with 0.34 more weekly park visits (95% CI 0.09, 0.59; p = 0.007). In other words, knowing where to go, valuing nature, and having time, and money contributed to increased likelihood of visiting a park. We discuss in terms of health behavior theory how demographics, knowledge, attitudes and perceived barriers to park use can inform park prescription interventions.
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Rosalki, S. B., and A. Y. Foo. "Incubation with neuraminidase and affinity electrophoresis with wheat-germ lectin compared for separating and quantifying alkaline phosphatase isoenzymes in plasma." Clinical Chemistry 31, no. 7 (1985): 1198–200. http://dx.doi.org/10.1093/clinchem/31.7.1198.
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Abstract Of 98 patients' specimens examined for alkaline phosphatase (EC 3.1.3.1) isoenzymes by electrophoresis on cellulose acetate membrane after incubation with neuraminidase, 50 showed only a single liver or bone isoenzyme staining band; in 15 of these, the tissue origin of the fraction could not be accurately identified from its electrophoretic location. In the remaining 48 specimens, both liver and bone fractions were identifiable, but in only 25 of these was the electrophoretic resolution sufficient to yield separate peaks on densitometry. In contrast, both liver and bone alkaline phosphatase isoenzymes were identified in 95 of the 98 specimens by affinity electrophoresis involving wheat-germ lectin, the detection of both fractions being in agreement with the results of sequential heat inactivation. The tissue origin of the enzyme bands was readily ascertainable from their consistent electrophoretic location in this medium, and in 89 of the specimens the isoenzyme fractions could be resolved into separate peaks on densitometry. We conclude that resolution of liver and bone alkaline phosphatase by incubation with neuraminidase followed by cellulose acetate electrophoresis is greatly inferior to that obtained by wheat-germ lectin affinity electrophoresis.
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Li, Xue, Marianna Porcino, Jingwen Qiu, Doru Constantin, Charlotte Martineau-Corcos, and Ruxandra Gref. "Doxorubicin-Loaded Metal-Organic Frameworks Nanoparticles with Engineered Cyclodextrin Coatings: Insights on Drug Location by Solid State NMR Spectroscopy." Nanomaterials 11, no. 4 (2021): 945. http://dx.doi.org/10.3390/nano11040945.
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Recently developed, nanoscale metal-organic frameworks (nanoMOFs) functionalized with versatile coatings are drawing special attention in the nanomedicine field. Here we show the preparation of core–shell MIL-100(Al) nanoMOFs for the delivery of the anticancer drug doxorubicin (DOX). DOX was efficiently incorporated in the MOFs and was released in a progressive manner, depending on the initial loading. Besides, the coatings were made of biodegradable γ-cyclodextrin-citrate oligomers (CD-CO) with affinity for both DOX and the MOF cores. DOX was incorporated and released faster due to its affinity for the coating material. A set of complementary solid state nuclear magnetic resonance (ssNMR) experiments including 1H-1H and 13C-27Al two-dimensional NMR, was used to gain a deep understanding on the multiple interactions involved in the MIL-100(Al) core–shell system. To do so, 13C-labelled shells were synthesized. This study paves the way towards a methodology to assess the nanoMOF component localization at a molecular scale and to investigate the nanoMOF physicochemical properties, which play a main role on their biological applications.
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Aamodt, E., R. Holmgren, and J. Culotti. "The isolation and in situ location of adligin: the microtubule cross-linking protein from Caenorhabditis elegans." Journal of Cell Biology 108, no. 3 (1989): 955–63. http://dx.doi.org/10.1083/jcb.108.3.955.
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Microtubules isolated from the nematode Caenorhabditis elegans contain long stretches of periodic cross-links formed by microtubule-associated proteins (MAPs). These cross-links are 5.7 nm long, 3 nm wide, and occur at one tubulin dimer (8-nm) intervals along the walls of microtubules (Aamodt, E., and J. Culotti, 1986. J. Cell Biol. 103:23-31). The structural protein of the cross-links was isolated from the MAPs by centrifugation and exclusion chromatography. The cross-links were formed exclusively from the most prevalent MAP, a 32,000 mol wt protein. We suggest the name adligin for this MAP. Adligin eluted from the exclusion column at 33,000 mol wt indicating that it was a monomer in solution. Antibodies were made against the purified adligin and affinity purified. The affinity-purified antibodies were used to locate adligin in situ and to determine its distribution relative to that of tubulin by the use of double label immunofluorescence. The anti-adligin antibodies labeled a fibrous network in the cytoplasm of most cells of C. elegans. Neurons were labeled especially well. This labeling pattern was similar to the labeling pattern obtained with antitubulin, but anti-adligin labeled some granules in the gut that were not labeled with antitubulin. These results suggest that adligin may be part of the interphase microtubule network in C. elegans.
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Mišković, Marija Zora, Marta Wojtyś, Maria Winiewska-Szajewska, et al. "Location Is Everything: Influence of His-Tag Fusion Site on Properties of Adenylosuccinate Synthetase from Helicobacter pylori." International Journal of Molecular Sciences 25, no. 14 (2024): 7613. http://dx.doi.org/10.3390/ijms25147613.
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The requirement for fast and dependable protein purification methods is constant, either for functional studies of natural proteins or for the production of biotechnological protein products. The original procedure has to be formulated for each individual protein, and this demanding task was significantly simplified by the introduction of affinity tags. Helicobacter pylori adenylosuccinate synthetase (AdSS) is present in solution in a dynamic equilibrium of monomers and biologically active homodimers. The addition of the His6-tag on the C-terminus (C-His-AdSS) was proven to have a negligible effect on the characteristics of this enzyme. This paper shows that the same enzyme with the His6-tag fused on its N-terminus (N-His-AdSS) has a high tendency to precipitate. Circular dichroism and X-ray diffraction studies do not detect any structural change that could explain this propensity. However, the dynamic light scattering, differential scanning fluorimetry, and analytical ultracentrifugation measurements indicate that the monomer of this construct is prone to aggregation, which shifts the equilibrium towards the insoluble precipitant. In agreement, enzyme kinetics measurements showed reduced enzyme activity, but preserved affinity for the substrates, in comparison with the wild-type and C-His-AdSS. The presented results reinforce the notion that testing the influence of the tag on protein properties should not be overlooked.
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Sherratt, Samuel, and R. Mason. "Fenofibric Acid has Distinct Molecular Location in Reconstituted Liver Membranes and Higher Affinity Compared to Pemafibrate." Journal of Clinical Lipidology 18, no. 4 (2024): e573-e574. http://dx.doi.org/10.1016/j.jacl.2024.04.111.
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Christ, George J., Brian Stone, and Arnold Melman. "Age-dependent alterations in the efficacy of phenylephrine-induced contractions in vascular smooth muscle isolated from the corpus cavernosum of impotent men." Canadian Journal of Physiology and Pharmacology 69, no. 7 (1991): 909–13. http://dx.doi.org/10.1139/y91-138.
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Steady-state contractile responses elicited by phenylephrine activation of the α1-adrenergic receptor subtype were studied in vascular smooth muscle strips isolated from the corpus cavernosum of impotent men. The dissociation constant of phenylephrine was determined by the method of partial irreversible receptor inactivation over a wide range of α1-adrenergic receptor alkylation levels. Statistical analysis of mean population values revealed a significantly greater mean efficacy for phenylephrine-induced contractions in older patients (60–73 years old) than in younger patients (40–59 years old), in the absence of similar alterations in the mean phenylephrine dissociation constant (affinity). In addition, there was no significant effect of the diabetic state on the mean phenylephrine affinity or efficacy estimates. However, despite the absence of age-or pathology-dependent variations in agonist affinity, as assessed by group mean calculations, a detailed examination of all isolated tissues on an individual basis revealed that the phenylephrine affinity estimates varied over a range of almost two orders of magnitude. Furthermore, a linear regression analysis revealed a highly significant positive correlation between agonist affinity and the location of the phenylephrine concentration–response curve, which was characterized by a slope significantly less than unity. In conclusion, an increased efficacy of phenylephrine-induced contractions in vitro is consistent with the hypothesis that augmented corporal vascular smooth muscle contractility in vivo may contribute to the pathophysiology of impotence in older patients.Key words: phenylephrine, α1-adrenergic receptor, human vascular smooth muscle, efficacy, impotence, corpus cavernosum.
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Neeld, Dennis, Jamie Rossjohn, and Brian Evavold. "Two dimensional affinity range correlates with phenotypic response to lipid antigens in iNKT cells (IRC4P.600)." Journal of Immunology 194, no. 1_Supplement (2015): 57.17. http://dx.doi.org/10.4049/jimmunol.194.supp.57.17.
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Abstract Invariant natural killer T cells (iNKT) are a unique group of T cells that possess an invariant T cell receptor (TCR) alpha chain paired with a limited repertoire of TCR beta chains that recognize lipid antigens presented by the MHC-I like molecule, CD1d. The micropipette adhesion frequency assay was used to define 2D affinities of iNKT cells for a panel of lipid:CD1d antigens. Despite having a limited diversity of αβ TCRs, NKT cells possess approximately a 100-fold range of affinities for the lipids tested. Our results show that αGalCer, an INFγ inducing lipid, has an approximately 10-fold higher affinity than OCH, an IL-4 skewing lipid in B6 mice. Moreover, thymic B6 iNKT cells, which predominantly produce Th1 cytokines (IFNγ), possessed a 4-fold higher affinity as compared to iNKT cells from Balb/C mice that favor more of a Th2 (IL-4) response. iNKT cell phenotype is also affected by their location as cells from the liver of Balb/C mice, which are predominantly IFNγ producers have a 2-fold increase in affinity for αGalCer compared to IL-4 predominant thymic iNKT cells. In addition to affinity differences related to phenotype, TCR expression levels of thymic derived iNKT cells reveal that Balb/C mice express twice as much TCR as the B6 mice. Taken together, these results indicate that NKT2 cytokine producing iNKT cells possess lower 2D affinity and higher TCR density compared to their NKT1 producing counterparts.
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MERNAGH, Darren R., Ian A. TAYLOR, and G. Geoff KNEALE. "Interaction of the type I methyltransferase M.EcoR124I with modified DNA substrates: sequence discrimination and base flipping." Biochemical Journal 336, no. 3 (1998): 719–25. http://dx.doi.org/10.1042/bj3360719.
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We have analysed the DNA–protein contacts made between the type I DNA methyltransferase M.EcoR124I and its recognition sequence. The effects of base modifications have been probed by measuring the affinity of M.EcoR124I for the modified sequences relative to that for the wild-type sequence by using gel-retardation competition assays. These results, along with those from methylation interference footprinting and photo-affinity cross-linking have identified the location of potential DNA contacts within the DNA recognition site. Substitution of 6-thioguanosine for each of the three specific guanines in the recognition sequence leads to a large (10–20-fold) decrease in the strength of DNA binding, indicating the importance of hydrogen-bonding interactions in the major groove of DNA. In contrast, replacement of either (or both) of the adenines at the target site for methylation by the enzyme, to produce either a base pair mismatch or loss of the base, leads to a marked increase in DNA-binding affinity. The results strongly support the proposal that type I methyltransferases employ a base-flipping mechanism to methylate their target base.
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Longo, Raffaele, Marialuigia Raimondo, Luigi Vertuccio, et al. "Bottom-Up Strategy to Forecast the Drug Location and Release Kinetics in Antitumoral Electrospun Drug Delivery Systems." International Journal of Molecular Sciences 24, no. 2 (2023): 1507. http://dx.doi.org/10.3390/ijms24021507.
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Electrospun systems are becoming promising devices usable for topical treatments. They are eligible to deliver different therapies, from anti-inflammatory to antitumoral. In the current research, polycaprolactone electrospun membranes loaded with synthetic and commercial antitumoral active substances were produced, underlining how the matrix-filler affinity is a crucial parameter for designing drug delivery devices. Nanofibrous membranes loaded with different percentages of Dacarbazine (the drug of choice for melanoma) and a synthetic derivative of Dacarbazine were produced and compared to membranes loaded with AuM1, a highly active Au-complex with low affinity to the matrix. AFM morphologies showed that the surface profile of nanofibers loaded with affine substances is similar to one of the unloaded systems, thanks to the nature of the matrix-filler interaction. FTIR analyses proved the efficacy of the interaction between the amidic group of the Dacarbazine and the polycaprolactone. In AuM1-loaded membranes, because of the weak matrix-filler interaction, the complex is mainly aggregated in nanometric domains on the nanofiber surface, which manifests a nanometric roughness. Consequently, the release profiles follow a Fickian behavior for the Dacarbazine-based systems, whereas a two-step with a highly prominent burst effect was observed for AuM1 systems. The performed antitumoral tests evidence the high-cytotoxic activity of the electrospun systems against melanoma cell lines, proving that the synthetic substances are more active than the commercial dacarbazine.
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Samsó, Montserrat, Ramon Trujillo, Georgina B. Gurrola, Hector H. Valdivia, and Terence Wagenknecht. "Three-Dimensional Location of the Imperatoxin a Binding Site on the Ryanodine Receptor." Journal of Cell Biology 146, no. 2 (1999): 493–500. http://dx.doi.org/10.1083/jcb.146.2.493.
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Cryo-electron microscopy and three-dimensional, single-particle image analysis have been used to reveal the specific binding site of imperatoxin A (IpTxa) on the architecture of the calcium release channel/ryanodine receptor from skeletal muscle (RyR1). IpTxa is a peptide toxin that binds with high affinity to RyR1 and affects its functioning. The toxin was derivatized with biotin to enhance its detection with streptavidin. IpTxa binds to the cytoplasmic moiety of RyR1 between the clamp and handle domains, 11 nm away from the transmembrane pore. The proposed mimicry by IpTxa of the dihydropyridine receptor (DHPR) II-III loop, thought to be a main physiological excitation-contraction trigger, suggests that the IpTxa binding location is a potential excitation-contraction signal transduction site.
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Maier, Irene, Robert H. Schiestl, and Georg Kontaxis. "Cyanovirin-N Binds Viral Envelope Proteins at the Low-Affinity Carbohydrate Binding Site without Direct Virus Neutralization Ability." Molecules 26, no. 12 (2021): 3621. http://dx.doi.org/10.3390/molecules26123621.
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Glycan-targeting antibodies and pseudo-antibodies have been extensively studied for their stoichiometry, avidity, and their interactions with the rapidly modifying glycan shield of influenza A. Broadly neutralizing antiviral agents bind in the same order when they neutralize enveloped viruses regardless of the location of epitopes to the host receptor binding site. Herein, we investigated the binding of cyanovirin-N (CV–N) to surface-expressed glycoproteins such as those of human immunodeficiency virus (HIV) gp120, hemagglutinin (HA), and Ebola (GP)1,2 and compared their binding affinities with the binding response to the trimer-folded gp140 using surface plasmon resonance (SPR). Binding-site knockout variants of an engineered dimeric CV–N molecule (CVN2) revealed a binding affinity that correlated with the number of (high-) affinity binding sites. Binding curves were specific for the interaction with N-linked glycans upon binding with two low-affinity carbohydrate binding sites. This biologically active assembly of a domain-swapped CVN2, or monomeric CV–N, bound to HA with a maximum KD of 2.7 nM. All three envelope spike proteins were recognized at a nanomolar KD, whereas binding to HIV neutralizing 2G12 by targeting HA and Ebola GP1,2 was measured in the µM range and specific for the bivalent binding scheme in SPR. In conclusion, invariant structural protein patterns provide a substrate for affinity maturation in the membrane-anchored HA regions, as well as the glycan shield on the membrane-distal HA top part. They can also induce high-affinity binding in antiviral CV–N to HA at two sites, and CVN2 binding is achieved at low-affinity binding sites.
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Cline, Erin G., and W. James Nelson. "Characterization of Mammalian Par 6 as a Dual-Location Protein." Molecular and Cellular Biology 27, no. 12 (2007): 4431–43. http://dx.doi.org/10.1128/mcb.02235-06.
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ABSTRACT Par 6 acts as a scaffold protein to facilitate atypical protein kinase C-mediated phosphorylation of cytoplasmic protein complexes, leading to epithelial and neuronal cell polarization. In addition to its location in the cytoplasm, Par 6 is localized to the nucleus. However, its organization and potential functions in the nucleus have not been examined. Using an affinity-purified Par 6 antibody and a chimera of Par 6 and green fluorescent protein, we show that Par 6 localizes precisely to nuclear speckles, but not to other nuclear structures, and displays characteristics of speckle proteins. We show that Par 6 colocalizes in the nucleus with Tax, a transcriptional activator of the human T-cell leukemia virus type 1 long terminal repeat, but multiple lines of evidence show that Par 6 is not directly involved in known functions of speckle proteins, including general transcription, splicing, or mRNA transport. Significantly, however, the structure of nuclear speckles is lost when Par 6 levels are reduced by Par 6-specific small interfering RNA. Therefore, we hypothesize that Par 6 in the nucleus acts as a scaffolding protein in nuclear speckle complexes, similar to its role in the cytoplasm.
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Lewis, D. A., and L. F. Bisson. "The HXT1 gene product of Saccharomyces cerevisiae is a new member of the family of hexose transporters." Molecular and Cellular Biology 11, no. 7 (1991): 3804–13. http://dx.doi.org/10.1128/mcb.11.7.3804-3813.1991.
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Two novel genes affecting hexose transport in the yeast Saccharomyces cerevisiae have been identified. The gene HXT1 (hexose transport), isolated from plasmid pSC7, was sequenced and found to encode a hydrophobic protein which is highly homologous to the large family of sugar transporter proteins from eucaryotes and procaryotes. Multicopy expression of the HXT1 gene restored high-affinity glucose transport to the snf3 mutant, which is deficient in a significant proportion of high-affinity glucose transport. HXT1 was unable to complement the snf3 growth defect in low copy number. The HXT1 protein was found to contain 12 putative membrane-spanning domains with a central hydrophilic domain and hydrophilic N- and C-terminal domains. The HXT1 protein is 69% identical to GAL2 and 66% identical to HXT2, and all three proteins were found to have a putative leucine zipper motif at a consensus location in membrane-spanning domain 2. Disruption of the HXT1 gene resulted in loss of a portion of high-affinity glucose and mannose transport, and wild-type levels of transport required both the HXT1 and SNF3 genes. Unexpectedly, expression of beta-galactosidase activity by using a fusion of the lacZ gene to the HXT1 promoter in a multicopy plasmid was maximal during lag and early exponential phases of growth, decreasing approximately 100-fold upon further entry into exponential growth. Deletion analysis of pSC7 revealed the presence of another gene (called ORF2) capable of suppressing the snf3 null mutant phenotype by restoring high-affinity glucose transport and increased low-affinity transport.
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Lewis, D. A., and L. F. Bisson. "The HXT1 gene product of Saccharomyces cerevisiae is a new member of the family of hexose transporters." Molecular and Cellular Biology 11, no. 7 (1991): 3804–13. http://dx.doi.org/10.1128/mcb.11.7.3804.
Full textAbstract:
Two novel genes affecting hexose transport in the yeast Saccharomyces cerevisiae have been identified. The gene HXT1 (hexose transport), isolated from plasmid pSC7, was sequenced and found to encode a hydrophobic protein which is highly homologous to the large family of sugar transporter proteins from eucaryotes and procaryotes. Multicopy expression of the HXT1 gene restored high-affinity glucose transport to the snf3 mutant, which is deficient in a significant proportion of high-affinity glucose transport. HXT1 was unable to complement the snf3 growth defect in low copy number. The HXT1 protein was found to contain 12 putative membrane-spanning domains with a central hydrophilic domain and hydrophilic N- and C-terminal domains. The HXT1 protein is 69% identical to GAL2 and 66% identical to HXT2, and all three proteins were found to have a putative leucine zipper motif at a consensus location in membrane-spanning domain 2. Disruption of the HXT1 gene resulted in loss of a portion of high-affinity glucose and mannose transport, and wild-type levels of transport required both the HXT1 and SNF3 genes. Unexpectedly, expression of beta-galactosidase activity by using a fusion of the lacZ gene to the HXT1 promoter in a multicopy plasmid was maximal during lag and early exponential phases of growth, decreasing approximately 100-fold upon further entry into exponential growth. Deletion analysis of pSC7 revealed the presence of another gene (called ORF2) capable of suppressing the snf3 null mutant phenotype by restoring high-affinity glucose transport and increased low-affinity transport.
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Jensen, Jan K., Klavs Dolmer, Christine Schar, and Peter G. W. Gettins. "Receptor-associated protein (RAP) has two high-affinity binding sites for the low-density lipoprotein receptor-related protein (LRP): consequences for the chaperone functions of RAP." Biochemical Journal 421, no. 2 (2009): 273–82. http://dx.doi.org/10.1042/bj20090175.
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RAP (receptor-associated protein) is a three domain 38 kDa ER (endoplasmic reticulum)-resident protein that is a chaperone for the LRP (low-density lipoprotein receptor-related protein). Whereas RAP is known to compete for binding of all known LRP ligands, neither the location, the number of binding sites on LRP, nor the domains of RAP involved in binding is known with certainty. We have systematically examined the binding of each of the three RAP domains (D1, D2 and D3) to tandem and triple CRs (complement-like repeats) that span the principal ligand-binding region, cluster II, of LRP. We found that D3 binds with low nanomolar affinity to all (CR)2 species examined. Addition of a third CR domain increases the affinity for D3 slightly. A pH change from 7.4 to 5.5 gave only a 6-fold increase in Kd for D3 at 37 °C, whereas temperature change from 22 °C to 37 °C has a similar small effect on affinity, raising questions about the recently proposed D3-destabilization mechanism of RAP release from LRP. Surprisingly, and in contrast to literature suggestions, D1 and D2 also bind to most (CR)2 and (CR)3 constructs with nanomolar affinity. Although this suggested that there might be three high-affinity binding sites in RAP for LRP, studies with intact RAP showed that only two binding sites are available in the intact chaperone. These findings suggest a new model for RAP to function as a folding chaperone and also for the involvement of YWTD domains in RAP release from LRP in the Golgi.
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Radic, M. Z., J. Mackle, J. Erikson, C. Mol, W. F. Anderson, and M. Weigert. "Residues that mediate DNA binding of autoimmune antibodies." Journal of Immunology 150, no. 11 (1993): 4966–77. http://dx.doi.org/10.4049/jimmunol.150.11.4966.
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Abstract Somatic mutations to arginine (R) are a common feature of a subset of J558 H chain genes that code for the majority of high-affinity, anti-dsDNA antibodies in autoimmune MRL/lpr mice. To examine the consequences of such amino acid substitutions on DNA binding, we reverted three somatic mutations of a prototypic anti-dsDNA H chain gene, VH3H9, and assayed the effect of those reversions by expression in a V lambda 1 L chain-only plasmacytoma line. Reversion of R53 eliminated virtually all dsDNA binding and sharply reduced ssDNA affinity. While the complete germ-line revertant of VH3H9 retained a low level of DNA binding, the substitution of R96, a product of N base addition in the third complementarity determining region (CDR3), with glycine (G) was sufficient to abolish measureable DNA specificity. Antibodies with higher affinity for DNA were generated by introducing arginines into VH3H9 at any one of four positions where somatic mutations to arginine had been identified by sequencing other anti-dsDNA J558 H chain genes. All four arginine mutants showed affinity increments consistent with their direct involvement in DNA binding, although one such mutant, K64R, required the simultaneous reversion of an adjacent aspartic acid (D) to the germ-line glycine. Two variants with three nongerm-line arginines showed further improvements in DNA affinity suggesting that their contributions to DNA binding may be additive. Molecular modeling of antibody and mutant F(ab) structures and calculations of their electrostatic potentials were used as an aid in interpreting the results and in predicting the location and size of possible combining sites.
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Popp, Roland, Tobias Kohl, Patricia Patz, Gaby Trautwein, and Ulrike Gerischer. "Differential DNA Binding of Transcriptional Regulator PcaU from Acinetobacter sp. Strain ADP1." Journal of Bacteriology 184, no. 7 (2002): 1988–97. http://dx.doi.org/10.1128/jb.184.7.1988-1997.2002.
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ABSTRACT Transcriptional regulator PcaU from Acinetobacter sp. strain ADP1 governs expression of genes for protocatechuate degradation (pca genes) as a repressor or an activator depending on the levels of the inducer protocatechuate and of its own gene. PcaU is a member of the IclR protein family. Here the DNA binding properties of the purified protein are described in terms of the location of the binding sites and the affinity to these sites. Native PcaU was purified after overexpression of the pcaU gene in Escherichia coli. It is a dimer in solution. The binding site in the pcaU-pcaI intergenic region is located between the two divergent promoters covering 45 bp, which includes three perfect 10-bp repetitions. A PcaU binding site downstream of pcaU is covered by PcaU across two palindromic sequence repetitions. The affinity of PcaU for the intergenic binding sites is 50-fold higher (dissociation constant [Kd ], 0.16 nM) than the affinity for the site downstream of pcaU (Kd , 8 nM). The binding of PcaU was tested after modifications of the intergenic binding site. Removal of any external sequence repetition still allowed for specific binding of PcaU, but the affinity was significantly reduced, suggesting an important role for all three sequence repetitions in gene expression. The involvement of DNA bending in the regulatory process is suggested by the observed strong intrinsic curvature displayed by the pcaU-pcaI intergenic DNA.
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Butterfield, John, Shari Sutor, Wendy Nevala, and Svetomir Markovic. "616 A novel non-covalent linker peptide with nanomolar affinity for clinical IgG1 antibodies preserves antibody-antigen affinity and drug potency against PDL1+ melanoma when conjugated with DM1." Journal for ImmunoTherapy of Cancer 8, Suppl 3 (2020): A652. http://dx.doi.org/10.1136/jitc-2020-sitc2020.0616.
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BackgroundAntibody-drug conjugates (ADC) increase the efficacy of current chemotherapeutics, decrease off site toxicity, and pair drug function with immunomodulatory effects. Current ADC platforms depend on the use of covalent linker molecules between the antibody and the drug of choice. This approach leads to significant variation in the number of drug molecules bound, the location of their binding, and inconsistency in maintaining the structure and antigen affinity of the antibody. Because of this, covalent-based ADC development requires extensive separation steps to isolate the ideal isotypes of the ADC. This testing and separation must be repeated for each antibody and each drug considered. Here we present a peptide that non-covalently binds multiple clinically relevant IgG1 antibodies at a controlled ratio and location, then demonstrate its use as a modular ADC linker platform.MethodsPeptide-antibody and antibody-antigen affinity were determined using Biacore surface plasmon resonance. Peptides conjugated with alexafluor or DM1 were purified using HPLC and structure was confirmed through mass spectrometry. Flow cytometry verified delivery of peptide-atezolizumab conjugates to C1861 PDL1+ melanoma cells. Peptide-DM1 potency was determined in-vitro using a calcein-AM and propridium iodine live/dead cell double staining.ResultsAntibody-Binding Peptide Linker (APL) was developed from a series of space filling amino acid substitutions at key residues on an 18-mer peptide derived from a hydrophobic pocket on human albumin (figure 1a). A lysine containing tail was added to the C-terminus for conjugation to small molecule therapeutics through amine coupling. APL has nanomolar binding affinity for the fab region of IgG1 antibodies including rituximab (KD= 1.85 × 10-8), bevacizumab (KD= 5.2 × 10-8), trastuzumab (KD= 8.87 × 10-8), and atezolizumab (KD= 3.78 × 10-8) (figure 1b). Kinetic binding models, performed by Biacore surface plasmon resonance, showed a 2:1 association of peptide to antibody. All four antibodies retained their antigen affinity when bound by APL (figure 2a). Labeling of APL with an alexafluor showed delivery to PDL1+ melanoma cells when given bound to the anti-PDL1 antibody atezolizumab (figure 2b). Conjugation of APL with the tubulin inhibitor DM1 (figure 2c) resulted in a drug conjugated peptide that retained the potency of the drug itself (figure 2d).Abstract 616 Figure 1a) APLinker peptide structure showing the hydrophobic side chains necessary for antibody binding (green), an isoleucine substitution to increase affinity (red), and the addition of a lysine residue to the C terminus for amine conjugation. b) Binding affinity of each peptide mutant to common therapeutic antibodies, determined using Biacore surface plasmon resonanceAbstract 616 Figure 2a) Affinity of clinical antibodies for their antigen when bound by APLinker peptide at different molar ratios. b) Labeling of PDL1+ C8161 melanoma cells with atezolizumab bound by AF647 conjugated APLinker. c) Structure of APLinker conjugated with the chemotherapeutic DM1 onto the C-terminus lysine using an SMCC crosslinker. d) In-vitro proliferation assay of DM1 alone and APL-DM1 conjugate using A-375 melanoma cells.ConclusionsAntibody-Binding Peptide Linker (APL) non-covalently binds clinical IgG1 antibodies at a fixed two to one ratio without affecting antigen affinity. Conjugation of APL with a drug of choice provides a modular Antibody-Drug Conjugate platform where both the antibody and drug can be substituted with ease.