Examples of four classes of CPPs and delivered cargoes. The list of cargo is not exhaustive and given for illustration. X = 7, 8, or 9 arginine residues.
\\n\\n
Released this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\\n\\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'IntechOpen is proud to announce that 179 of our authors have made the Clarivate™ Highly Cited Researchers List for 2020, ranking them among the top 1% most-cited.
\n\nThroughout the years, the list has named a total of 252 IntechOpen authors as Highly Cited. Of those researchers, 69 have been featured on the list multiple times.
\n\n\n\nReleased this past November, the list is based on data collected from the Web of Science and highlights some of the world’s most influential scientific minds by naming the researchers whose publications over the previous decade have included a high number of Highly Cited Papers placing them among the top 1% most-cited.
\n\nWe wish to congratulate all of the researchers named and especially our authors on this amazing accomplishment! We are happy and proud to share in their success!
\n'}],latestNews:[{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"},{slug:"intechopen-books-hosted-on-the-mathworks-book-program-20200819",title:"IntechOpen Books Hosted on the MathWorks Book Program"},{slug:"intechopen-s-chapter-awarded-the-guenther-von-pannewitz-preis-2020-20200715",title:"IntechOpen's Chapter Awarded the Günther-von-Pannewitz-Preis 2020"}]},book:{item:{type:"book",id:"5921",leadTitle:null,fullTitle:"Textiles for Advanced Applications",title:"Textiles for Advanced Applications",subtitle:null,reviewType:"peer-reviewed",abstract:"This book presents a global view of the development and applications of technical textiles with the description of materials, structures, properties, characterizations, functions and relevant production technologies, case studies, challenges, and opportunities. 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Currently, he is appointed as Assistant Professor in The Department of Textile Technology at IIT Delhi, India. Prior to joining IIT Delhi, he was working as Research Assistant Professor (2016-2017) at The Hong Kong Polytechnic University, Hong Kong. He also served as a cultural ambassador (2014-2016) in USA at The University of California Davis via the prestigious Fulbright Fellowship program. He is the first recipient from India to be selected for the Fulbright Postdoctoral Program (2013) in the field of textiles.\r\n\r\nHis main research focuses on smart fibrous/polymeric materials and related fabric structures. He has over 30 publications in leading refereed SCI journals of materials, textiles and medical fields, 2 patents, 2 authored books, 10 book chapters, and over 20 conference proceedings. He holds editorial membership of 3 international referred journals including JEFF, FTEE and CTFTTE. 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Once steel and concrete framing systems replaced bearing wall systems, especially for multistory buildings, masonry walls were then used as infill walls (Figure 1) to provide the envelope and partition wall functions. Besides such functions, the role of masonry infill walls in seismic resistance of buildings has long been well recognized. In fact, because of participation of masonry infill walls in resisting lateral seismic loads, infill walls and/or their framing systems can sustain damage with life-safety hazard potential [1, 2].
\nExamples of masonry infill wall in a reinforced concrete frame building [Photo by Ali M. Memari].
Traditionally, masonry infill walls are specified by architects as exterior envelope walls, backup walls for veneer systems, or interior partition walls. Such construction does not carry gravity load from floors and only carries its own weight. Depending on the details of joints between the edges of infill walls and infilled frames, the interaction between the infill wall and frame can adversely affect the seismic behavior of the structure (e.g., [3, 4]). In most cases, the small gaps between the infill wall and the structural frame are infilled with caulking and in some cases with mortar [5]. This tight-fit construction (Figure 2) engages the infill wall in in-plane lateral load resistance [6]. Depending on whether the wall is solid (complete infill) or the existence of large openings that make the infill wall partial infill, the wall’s interaction with confining frames could possibly lead to premature column failure as a result of short column effect or to increased levels of ductility demand in columns. Furthermore, because these tight-fit infill walls essentially behave as shear walls, their distribution in plan could increase torsional moments and create structural irregularities, if not placed symmetrically. The manner infill walls resist lateral loads is much like a compression brace, and the cyclic interaction of this effective brace with structural frame connection may lead to either the failure in the masonry and/or damage to the beam-column connection. Tight-fit construction of infill walls, whether of partial height or full height can lead to extensive damage to walls, columns, or beam-column joints. Besides the life-safety hazard that such damage will pose, in terms of financial loss, infill wall damage and subsequent repair/replacement work can seriously challenge building owners and tenants.
\nExample of a tight-fit masonry infill wall construction [Photo by Ali M. Memari].
In order to avoid damage to infill walls, columns, or joints, the use of gaps between the infill wall and the frame is one alternative as shown in Figures 3 and 4. Providing gaps between the infill wall and the confining frame is a building code requirement (e.g., [7]) if the infill wall is not designed as part of the lateral force-resisting system, that is, if it is a nonparticipating infill. On the other hand, if the in-plane isolation joints are not large enough to satisfy the conditions for nonparticipating infills, then the infill wall is considered as part of the primary lateral force-resisting system, that is, participating infill, and it must be designed as a shear wall, which complicates design and construction and is not typically desirable by designers. For isolation of infill walls, small gaps (e.g., 9.5 mm–12.7 mm) are usually provided, which are then filled with caulking or other deformable fillers. Figure 3 shows an example of an infill wall construction with isolated joints from the frame with small gaps. In more seismically active areas, larger gaps are usually provided, as shown in the example of Figure 4, which shows a large gap between concrete masonry unit (CMU) infill wall and reinforced concrete frame. This particular infill wall was, however, intended to function as the backup wall for brick veneer exterior skin. In general, when such a gap is to be provided, the gap size should exceed the expected interstory drift, which is determined either by structural analysis, or as the maximum allowable value specified in the building code.
\nExample of partition infill wall isolated from the frame with small gaps: (a) beam-column joint area and (b) gap between column and infill wall [Photo by Ali M. Memari].
Use of large gaps between infill backup wall and frame in a Seattle building: (a) view of several stories of the building and (b) close-up view of gaps between column and infill walls [Photo by Ali M. Memari].
Providing large gaps for partition wall applications will cause its own challenging issues with respect to fire safety and sound transmission issues for which the architect and designers should recommend appropriate solutions. Providing small gaps in general will not have the scale of the problems of large gaps. However, under moderate-to-strong earthquakes, the gap openings will likely approach the upper limit for story drift ratios of building codes such as ASCE 7–16 [8]. For instance, for a Risk Category II building with allowable story drift ratio of 2%, the upper limit will be nearly 75 mm for a 3750 mm story height. In that case, once the gap opening is overcome by the frame story drift, the columns will then bear against the infill wall, and under cyclic-type oscillations, the infill wall and/or frame members can sustain damage. It is the responsibility of the designer to assure the sufficiency of the gap size, and if it is desirable to keep the gap size small, the designer will have to increase the size or number of frame members designated as part of the lateral-force-resisting system, which could translate to substantial increase in construction cost.
\nBy isolating the infill wall from the frame and avoiding their interaction in buildings with moment-resisting frames as their primary lateral force-resisting system, damages to infilled frames, failure of infill walls, and potential life-safety hazards can be avoided. However, in that case, the building is deprived of the potential benefit from the strength and stiffness that masonry infill walls can offer even if they are not designed as shear walls. It should be noted that even unreinforced masonry walls inherently possess considerable stiffness that can be properly and advantageously employed in lateral force resistance.
\nOne shortcoming of this isolation option is that the beneficial effects of the masonry infill in stiffening and strengthening the structural frame system will not be employed. In general, since the masonry infill walls are heavy and greatly increase the effective seismic weight of the building, it would be logical to engage them also in lateral load resistance. However, it is the potential damage to these brittle components that designers wish to avoid. The compromise solution seems to be a controlled engagement of the masonry infill walls by employing a structural fuse concept. Such an idea is based on desirability of employing beneficial effects of strength and stiffness of infill walls to reduce story drifts during seismic events up to certain controlled levels. Under strong shaking, when the interaction force between the infill wall and the frame exceeds a certain level, it is desirable to isolate the infill wall from the frame in order to avoid damage to the wall or the frame. This function is provided by using a structural fuse.
\nIn this chapter, preliminary studies on this concept are reviewed. Initially, the concept of the masonry infill structural fuse is explained. This is followed by discussion of experimental tests on different types of fuse elements. Next, the pilot experimental studies employing a one-fourth scale frame and infill walls with fuse are reviewed. The results of computer-modeling studies are then presented followed by recommendations for additional follow-up studies that need to be undertaken.
\nThere has been over 60 years of research on infill walls. The following references are mentioned as chronological representative examples of the experimental and analytical studies done over the past six decades: [2, 5, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48]. Even after such extensive international efforts, there is still room for enhanced understanding and design considerations of masonry infill wall interaction with structural frame.
\nThe consensus among researchers is that it is wise to use the beneficial properties of the infills in design if their strength and stiffness characteristics can be relied on. The masonry design code, ACI 530–13/ASCE 5–13/TMS 402–13 [7], provides design guidelines for infill walls in Appendix B. The current code offers two sets of prescriptive design guidelines, one for masonry walls not considered participating in lateral force-resistance, and the other for walls that are expected to take part in lateral force resistance. For the latter group, masonry standards joint committee (MSJC) 2013 code requires these walls to be designed as shear walls, which necessitates use of sufficient reinforcement and detailing to satisfy in-plane and out-of-plane flexural and shear effects. According to the code, for the former group B2.1.1: In-plane isolation joints shall be designed between the infill and the sides and top of the bounding frame., B2.1.2: In-plane isolation joints shall be specified to be at least 3/8 in. (9.5 mm) wide in the plane of the infill, and shall be sized to accommodate the design displacements of the bounding frame., B2.1.3: In-plane isolation joints shall be free of mortar to contain resilient material, provided that the compressibility of that material is considered in establishing the required size of the joint. In practice, sometimes gaps of different sizes are provided (most likely not by design but because of construction issues) between the infill and the frame as shown in Figure 5 in a building.
\nUse of different size gaps in a building [Photo by Ali M. Memari].
In search of ways to find an alternative solution so that the infill wall can participate in lateral load resistance and provide additional stiffness for wind loading and low-to-moderate seismic events, but to disengage (be isolated) under major events, a fuse concept was introduced [49]. Figure 6 shows the concept of a structural fuse placed between the infill wall and structural frame. The fuse element is placed as a masonry unit (or part of it). Depending on the fuse element material and mechanism design, it can have stiffness and damping properties and it could be a single rigid-brittle element or a rigid-ductile element.
\nSchematic representation of fuse elements in a masonry infill wall [53].
Pilot tests were carried out to investigate the concept and the feasibility of using such a fuse for infill walls [50, 51, 52]. A few different materials and mechanisms were studied to develop a potentially acceptable fuse element. The concept of a disk and a punching or penetrating rod was developed. In this concept, a disk of concrete or wood will be used as the breakable fuse element as shown in Figure 7. The fuse element types shown in Figure 7 perform in a rigid manner up to their punching capacity, beyond which, the interaction between the frame and the infill wall stops. In other words, when the fuse is installed between the top of the infill wall and the frame columns, the infill wall is engaged in lateral load resistance, but when the fuse breaks at the threshold design load of the fuse, the infill wall no longer offers resistance to lateral movement of the frame.
\nRigid fuse element with concrete and wood disk alternatives: (a) concrete disk; (b) wood disk; (c) engagement of steel rod on concrete disk; (d) engagement of steel rod on wood disk [53].
Another pilot study used rigid wood disks on a one-fourth scale three-story two-bay frame as shown in Figure 8. The pilot study investigated a rigid fuse element that worked only under compression. Figure 8 shows how a wood disk breaks when its ultimate capacity is reached. The size of the gap between the infill walls and the frame shown in Figure 8 was chosen for convenience of experimental study. For real applications in buildings, the fuse-holding mechanism will be placed in the location of an edge masonry unit, and therefore, normal gap sizes can be used. Furthermore, the out-of-plane movement of the infill wall can be restricted using different available mechanisms as appropriate to a given design.
\nTest results on one-fourth scale frame and infill wall with wood disk fuses: (a) one-fourth scale experimental setup; (b) steel rod tightened against wood fuse; and (c) steel rod puncturing wood fuse [53].
The process of pilot study leading to the test specimen shown in Figure 8 consisted of initially developing load-deformation relations for isolated disk element to obtain the average capacities. Then isolated masonry walls were tested under in-plane shear loading to determine their capacities. Finally, the fuse disks were chosen such that they will break prior to masonry infill shear capacity. The detail of the experimental study is explained in Ref. [53]. In this chapter, only the computer-modeling aspect of masonry infill walls equipped with rigid-brittle structural fuse elements is presented. The objective of this chapter is to discuss development of a finite element model for the system (infill-fuse-frame) and validate it by using the results of tests on masonry infill walls (without fuse) available in the literature. In the process of developing the finite element modeling, initially a single-bay, single-story steel frame with tightly fitted infill wall that has been studied by others was modeled. Once the single-bay, single-story model was validated using existing literature results, the model was subjected to monotonic pushover loading as well as cyclic loading under different load-control and displacement-control parameters. The presentation also includes discussion of a parametric study. Practical design approaches and guidelines for masonry infill walls equipped with the proposed structural fuse element and variation of masonry type for the fuse concept are presented in Refs. [54, 52].
\nIn the finite element model, material nonlinearities were considered because of nonlinear moment-rotation and force-deformation responses of steel frame connections, equivalent infill wall struts, tie-down anchors, and the fuse element. Large deformation and geometrical nonlinearities existed due to movements and contact between infill wall and frame. In this study, ANSYS finite element analysis program [55] was employed. Five different finite element types from ANSYS element library were used for modeling. The uniaxial BEAM3 element with compression, tension, and bending modeling capabilities was used to model the frame members. PLAIN42 element was used to model the masonry infill wall. CONTACT12 element was employed to model the interaction between infill and frame, and COMBIN39 spring element was considered to model the diagonal strut representing the masonry infill and rotational spring representing beam-column joint. Finally, COMBIN40 element was used to model the proposed structural fuse component.
\nTo model a bare steel frame, BEAM3 element with three degrees of freedom (two translations and one rotation) at each node was used. PLAIN42 element with four nodes and two translational degrees of freedom per node was used as a plane stress element to model the infill wall. COMBIN39 element with two nodes and with up to three translational degrees of freedom per node can be used as a unidirectional element (e.g., uniaxial compression-tension element or purely rotational spring). The longitudinal option with two degrees of freedom per node was used to model the diagonal struts to represent effective infill and also tie-down rebars. The rotational option was used to represent the frame’s beam-column connection. CONTACT12 element with two nodes and two translational degrees of freedom at each node was considered to model a gap between two surfaces, which can be in compression contact or at no contact and may also slide relative to each other considering Coulomb friction. This element was used to model the interaction between infill wall and frame when equipped with fuse. When there is interaction between the two surfaces, the normal stiffness and tangential (shear) stiffness may be active. A negative normal force represents contact between the two surfaces through a linear spring, while a positive normal force means lack of contact. On the other hand, when there is a negative force and the tangential force is less than the product of the normal force and friction coefficient, the two surfaces do not slide freely and are governed by the tangential spring stiffness. However, the two surfaces slide when the tangential force equals that product. COMBIN40 element is a special element to provide stiffness and damping to one side of a gap modeled in series. This two-node element with one degree of freedom per node (e.g., translational or rotational) can be specialized for different applications by appropriate assignment of values for spring stiffness coefficients, damping coefficient, mass value, gap size, and a limiting sliding force.
\nFrom the result of a comprehensive review of experimental and analytical studies on infill wall systems [22], an appropriate specimen was chosen for development of finite element modeling in this work. The approach for finite element model validation consisted of initially modeling the bare steel frame, then adding brace elements following methods in Refs. [56] (single-diagonal strut model) and [57] (three-diagonal strut model). The last step in developing the model was to add fuse elements.
\nOne of the specimens in the tests in Ref. [58] on single-bay, single-story steel frame with CMU infill walls (labeled WD7) was chosen for finite element modeling. The specimens selected are described in detail in Ref. [22]. Lateral load was applied to the frame at the top. Specimen WD7 [58] included CMU infill wall with standard horizontal bed joint reinforcement constructed without any gaps between the infill and the steel frame. Load-deflection diagram for the specimen is shown in Figure 9 including the bare frame and infilled frame tests. The figure also shows analysis results discussed subsequently.
\nLoad-deflection relation for single-bay, single-story system [53].
The bare frame was modeled as shown in Figure 10(a) using the finite elements as explained in the previous section. The trilinear moment-rotation relationship proposed in Ref. [57] was used for the beam-column joints. The load–displacement diagram for the model when subjected to monotonically increasing displacement was quite close to the experimental results. The bare frame showed to have an initial stiffness of about 3.22 kN/m. The failure mechanism consisted of formation of four plastic hinges in the four beam-column connections, which are represented by rotational springs in the model (Figure 10(a)).
\nANSYS models for (a) bare frame; (b) infilled steel frame with single-diagonal strut model; and (c) infilled steel frame with three-diagonal strut model [53].
The infill wall was modeled initially using the single-diagonal strut model [56] shown in Figure 10(b). This was accomplished by adding a nonlinear diagonal compression strut to the bare frame model. However, the nonlinear rotational springs at the beam-column joint were substituted by frictionless hinges, in order for the diagonal strut to take the entire lateral load. The force-deformation model [56] was used for the strut representing the infill wall. The three-diagonal compression strut [57] shown in Figure 10(c) was also used as a second alternative for infill model. The force-deformation models were developed based on equations in Ref. [57] using the geometry and material properties of the modeled specimen (WD7). The infilled frame models with the two types of strut models were subjected to monotonically increasing displacement with load-deflection plots compared to the experimental test results shown in Figure 9. The results of the two strut models show notable differences which is due to the assumptions made for force-deformation properties of the strut element. The three-diagonal strut model shows closer analytical results to the experimental test results.
\nThe next step in completing the finite element model (shown in Figure 11) was to add appropriate fuse elements and hold-down elements. At the location of the fuse element on the columns, two nonlinear rotational springs were added. The final steel frame model shown in Figure 11 had a total of 33 BEAM3 elements and 6 COMBIN39 elements. The masonry infill wall was, then, modeled with PLAIN42 elements. To model the contact between infill wall and steel frame, CONTACT12 elements were added at top and bottom at each side. The model presented also shows vertical steel rebar hold-downs modeled with COMBIN39 elements with tension force-deformation properties shown in Figure 12. The bottom corners of the infill wall were assumed to be in tight fit connection with the columns to provide shear transfer. The micro infill wall modeling required 396 PLAIN42 elements, 27 CONTACT12 elements, and 2 COMBIN39 elements.
\nANSYS model for infilled steel frame with fuse elements [53].
Force-deformation responses for tie-down steel rebar [53].
The fuse element used in the model is intended to simulate an elastic behavior up to failure or breakage of the element as shown in Figure 13. Once the fuse element breaks, there is no force transfer through the fuse element. COMBIN40 element provides the required property, which is transfer of force only in compression. To provide for such behavior, a very small value (0.0025 mm) was assumed for the GAP specification in the element property data. The spring K1 in the COMBIN40 element was determined considering the force-deformation results of the fuse elements pilot tests. COMBIN40 element features “break-away” property appropriate to simulate the condition of fuse breakage with subsequent zero force in the element, once the fuse capacity is reached. The fuse capacity is a function of the masonry infill wall shear strength. According to test results in Ref. [56], the infill wall had a capacity of 383 kN, which with a factor of safety of 4.0, yields a fuse capacity of 89 kN for the model. This value was used to specify FSLIDE, for which a negative value results in a drop to zero when the force in the element reaches the specified capacity (89 kN), while a positive value represents yielding or constant force equal to the capacity. In this case, only negative value was assigned.
\nForce-deformation responses for the rigid-brittle fuse element [53].
Pushover analysis of single-bay, single-story infilled frame with fuse element model was carried out to compare the response with infilled frame without fuse element. The results of this analysis are shown in Figure 9 along with the results from the experimental study of the bare frame and infilled frame. For better clarity, Figure 14 shows the plot of the initial deflection portions with larger scale. The effect of varying the fuse capacity on the system response is illustrated in Figure 9 with three different values for the fuse capacity (i.e., 89 kN, 178 kN, and 267 kN). The figure shows two stages of response consisting of (a) prior to breakage of the fuse and (b) after breakage. During the first stage shown by line OA in Figure 14, the fuse transfers lateral loads from the frame to the infill wall and as such, the slope of the line OA represents the combined larger stiffness of the steel frame and the masonry infill wall. Upon breakage of the fuse at point A (capacity of fuse), there is sudden drop in the force level, line AB, followed by load-deflection relation along BC, which represents the response of the bare frame. This means that the infill wall is disengaged from the steel frame and only the bare frame is resisting the total load.
\nLoad-deflection relation for single-bay, single-story model with “brittle-failure” fuse element [53].
Comparison of the response of the model having fuse element with those of the bare frame and infilled frame in Figure 9 shows that the stiffness of the system with fuse element is slightly smaller than that resulting from tested infilled frame (about 75% of the infilled frame). This, however, is about ten times the stiffness of the bare frame. Although as shown in Figure 9, higher strength fuse elements increase the strength capacity of the system, but it should be noted that the objective is to prevent failure of the wall. For example, based on the test results (shown on the figure), the tightly fitted masonry infill wall cracks around a lateral load of 378 kN. The smaller the fuse capacity, the larger will be the margin of safety against cracking.
\nThe fuse element model shown in Figure 13 describes a condition where upon breakage of the fuse, the force transfer across the fuse becomes zero. Since this could imply a shock-type response, but which is more like cracking of reinforced concrete or masonry system, it is possible to develop fuse elements that show more ductile response. For example, if the fuse element can be described by the trilinear or multilinear models shown in Figure 15, the corresponding load deflection plots for the infilled frame will be those shown in Figures 16 and 17, which show a more gradual drop of the force across the fuse and a smoother transition to the bare frame condition. It should be noted that depending on the mechanism of failure or design function of the fuse, different types of infilled frame response can be obtained. Examples of such mechanisms could include friction damper mechanism for energy dissipation and enhanced seismic response of the structure.
\nAssumed force-deformation responses for fuse element (a) “trilinear” and (b) “multilinear” [53].
Load-deflection relation for single-bay, single-story case study with “trilinear” response for fuse element [53].
Load-deflection relation for single-bay, single-story case study with “multilinear” response for fuse element [53].
With the finite element model validated based on the performance of a single-bay, single-story infilled frame, the modeling approach can next be applied to a multi-bay, multistory system. The same modeling features presented in previous sections were used to model the two-bay, three-story frame shown in Figure 18. The panel dimensions and material properties were the same as those for the single-bay, single-story case. The steel frame members, however, were modified to make them appropriate for a three-story structure. The masonry infill walls were assumed to be conventional CMU blocks (200 mm x 200 mm × 400 mm).
\nTwo-bay, three-story model description [53].
Models were developed for two-bay, three-story systems for three cases of bare frame, infilled frame without fuse, and infilled frame with fuse elements. The bare frame model shown in Figure 19(a) employed nonlinear beam-column joints shown in the figure by COMBIN39 elements. The model with masonry infill without fuse shown in Figure 19(b and c) consisted of two cases of single-diagonal strut and three-diagonal strut representation of the infill wall. Figure 20 shows the moment-rotation section behavior assumed for beam and column sections. For the single-strut case, the force-deformation behavior model shown in Figure 21 was used, while for the three-strut case, the models proposed in Ref. [57] were considered. The finite element model for the infilled frame with fuse elements is shown in Figure 22, where the elements used consist of 110 BEAM3 elements for the frame, 50 COMBIN30 elements for nonlinear joints, 606 PLAIN42 elements for masonry infill, 108 CONTACT12 elements for wall and frame connections, 12 COMBIN39/40 elements for fuse, 12 COMBIN40 elements for gap modeling, and 12 COMBIN39 elements for tie-downs.
\nANSYS models for two-bay, three-story case study: (a) bare steel frame; (b) single-diagonal strut method; and (c) three-diagonal strut method [53].
Moment-rotation response for joints [53].
Force-deformation response for diagonal strut of single-diagonal strut model [53].
ANSYS model for two-bay, three-story infilled frame with fuse elements [53].
The loading applied to the four models described consisted of imposing incremental horizontal in-plane displacement at the third floor level in a displacement-controlled mode. The resulting load-deflection diagrams for all four models are plotted in Figure 23. The results shown are consistent with the type of response observed for the single-bay, single-story in Figure 9. The results for the infilled frame with fuse element are also shown with three different fuse capacities. Figure 24 shows the enlarged plot of the fuse-equipped system compared to the bare frame model, while Figure 25 shows the sequence of fuse breakages. As expected, the load-deflection diagram for the system with fuse shows that after the breakage of the last fuse, the response closely follows the bare frame diagram. It should be added that such deflection will continue until the clearance between the frame and the infill wall is overcome, at which point the frame will directly bear against the infill wall, and the overall system will again experience high stiffness due to re-engagement and participation of infill wall.
\nLoad-deflection relation for single-bay, single-story system [53].
Load-deflection relation for two-bay, three-story infilled steel frame with “brittle-failure” fuse elements [53].
Behavior and failure mechanism of two-bay, three-story infilled steel frame with fuse system [53].
The displacement-controlled load application is useful to understand the behavior of the system as each fuse breaks, and in general for experimental tests studies to collect detailed data at each displacement increment. To simulate more realistic earthquake loading conditions and also for design purposes, however, load-controlled application can be a better choice. The two-bay, three-story model of the infilled frame with fuse elements was subjected to such a load-controlled case. Consistent with the first-mode deflection and story lateral loads, in-plane loads of F/2, F/3, and F/6 were considered at the third, second, and first floor levels, respectively, and applied incrementally. The resulting load-deflection diagram is shown in Figure 26 and the sequence of fuse breakage is graphically shown in Figure 27. Figure 26 shows that upon the breakage of the last fuse (third story), the response follows that of the bare frame. The results in Figure 26 show the beneficial effects of using fuse on increasing the stiffness and thus reducing in-plane deflection. Desirable sequence of fuse failure can be obtained by appropriate distribution of fuses with predetermined varying capacities over the height.
\nLoad-deflection relation for two-bay, three-story infilled steel frame with “brittle-failure” fuse elements (load control) [53].
Behavior and failure mechanism of two-bay, three-story infilled steel frame with fuse system (load control) [53].
In addition to described analytical studies, parametric studies were conducted to determine the effect of varying the structural frame joint rigidities, member strengths, as well as the location and stiffness of fuse elements. The moment-rotation model used for beam-column connection is shown in Figure 28, where the initial stiffness is Kj = Mpl/φel. By varying the rotation φel values from 0.0001 rad for a rigid frame to 100 rad for a pinned frame, the effects of joint stiffness on the response were evaluated. The results of the analysis for the two-bay, three-story frame are shown in Figure 29, which shows that by reducing the stiffness of the joints, the frame becomes more flexible. However, the effect on fuse performance is minor.
\nThree-linear moment-rotation response for joints [53].
Load-deflection relation for two-bay, three-story infilled steel frame with fuse system with different connection rigidity (stiffness) [53].
Next, by changing the size of the frame members, for a rigid frame, the member size effect on fuse equipped infilled frame performance were studied. Such behavior for the two-bay, three-story frame with different member sizes is shown in Figure 30. The initial design consisted of W12x53 for columns and W10x30 for beams, and the variation includes two cases of heavier and two cases of lighter sections. The results of the analysis show that heavier frame members provide stiffer and stronger system as a whole and that with stronger frames, fuse breaks at lower displacements. The results also show that the strength of the fuse elements should be consistent with that of frame, that is, a frame with higher ultimate load capacity should be used with fuse elements with larger capacity.
\nLoad-deflection relation for two-bay, three-story infilled steel frame with fuse system with different frame Strengths [53].
The effect of varying the vertical position of fuse elements with respect to the top of the wall was also examined. Four positions consisting of the wall top corner, 300 mm, 600 mm, and 900 mm below the top corner were chosen. The results of the analysis of the two-bay, three-story frame are illustrated in Figure 31, which show that the lower the position of fuse element, the larger the frame drift at fuse breakage points. The results also show that by lowering the position of the fuse, the initial stiffness of the entire system will be reduced and the fuse breaks at larger deflection. It can be concluded that higher positions enhances the effectiveness of the fuse function. Finally, in order to examine the effect of the fuse stiffness on the overall response, four different stiffness values were chosen for fuse elements and the results of the analysis of the two-bay, three-story frame are shown in Figure 32, which show that for fuse with lower stiffness, the load and deflection at fuse breakage increases. It can therefore be concluded that the stiffness of the fuse element can have a notable effect on the response of infilled frame.
\nLoad-deflection relation for two-bay, three-story infilled steel frame with fuse system with varying location for fuse element [53].
Load-deflection relation for two-bay, three-story infilled steel frame with fuse system with different stiffness for fuse elements [53].
The study presented has shown that existing commercial software (such as ANSYS or other similar software) can be used to effectively model complex use of masonry walls. The study has shown how various finite elements can be used to model masonry, structural fuse, as well as infilled frame for analysis under in-plane lateral loading. The available library of finite elements seems to be well-developed for this purpose. Aside from concluding the appropriateness of existing of modeling capabilities to capture various behavioral aspects of masonry infills used in conjunction with fuse elements, some conclusions and remarks can also be mentioned related to the proposed use of fuse concept to mitigate damage to masonry infill walls and/or infilled frames. The concept of using structural fuse elements as sacrificial components in masonry construction is practical and should be given consideration for follow-up R&D studies and more refined design and detailing for practical application. The use of finite element modeling for parametric study of the proposed concept has shown that the effect of frame joint stiffness on the overall mode of behavior is not as much as the stiffness of the frame members. The latter affects the design of the fuse capacity, and for a given frame stiffness, the overall behavior will be sensitive to the fuse capacity. The finite element model analysis also showed that higher positions of the fuse element add efficiency to fuse element performance. While the presented study focused on proof of the concept for masonry infill within steel frames, the concept is equally applicable for concrete frames as well. In fact, variations of the presented concept can be expanded to develop energy dissipating fuse systems for application to steel and concrete frames as well as light frame construction infilled with other materials than masonry.
\nA novel approach to overcome cell membrane impermeability and to deliver a large variety of particles and macromolecules into cells has been recently emerged, which is called cell-penetrating peptides (CPPs), also known as protein transduction domains (PTDs) [1, 2]. CPPs are generally short (up to 30 amino acids in length) water-soluble, cationic, and/or amphipathic peptides which make them promising vectors for therapeutic delivery, leading to a considerable amount of research focused on the intracellular delivery of drugs [3, 4, 5]. There are two principal types of CPPs that have been utilized for this purpose: (i) cationic CPPs, composed of short sequence of amino acids (arginine, lysine, and histidine). The indicated amino acids give the cationic charge to the peptide and permit its interaction with anionic motifs on the plasma membrane by a receptor-independent mechanism. (ii) amphipathic peptides, which have lipophilic and hydrophilic tails that are responsible for a direct peptide translocation mechanism across the plasma membrane [6].
The most important characteristic of CPPs is that they are able to translocate the plasma membrane at low micromolar concentrations in vivo and in vitro without using any receptors and without causing any significant membrane damage [7, 8]. Other benefits of using CPPs for therapeutic delivery are the absence of toxicity as compared to other cytoplasmic delivery devices, such as liposomes, polymers, etc. [6]. The mechanism for the CPP-facilitated cellular uptake remains not clear and depends on cargo and cellular type [9]. Due to its high density of basic amino acid residues (Arg and Lys), the large charge at physiological pH excludes the passive diffusion of CPPs across the lipid bilayer. Furthermore, it seems that classical uptake mechanisms such as protein-based receptors and transporters are not involved. On the contrary, endocytosis was shown as a common uptake mechanism, but is controversial at the same time. For example, in a number of reports, CPP uptake was not inhibited at 4°C or in the presence of inhibitors of endocytosis; in contrast, a capture of CPPs in the endocytotic vesicles was observed when soluble heparin sulfate was added [9, 10]. Many other studies indicate that aggregation of the cell surface glycosaminoglycan heparan sulfate (HS) is an important element in the uptake mechanism [2]. The challenge of the strategy using CPPs should take into consideration the size, stability, nonspecific versus specific associations, and potency versus toxicity that all play an important role for the selection of delivery systems [5].
The CPPs are initially discovered in 1965 when it was observed that histones and cationic polyamines such as polylysine stimulate the uptake of albumin by tumor cells in culture. It was shown that the conjugation of polylysine to albumin and other proteins enhances their transport into cells. Moreover, a comparison study of different homopolymers of cationic amino acids demonstrates that medium-length polymers of arginine enter cells more effective than similar-length polymers composed of lysine, ornithine, or histidine [11]. In 1988, it was discovered that the human immunodeficiency virus type 1 (HIV-1) encoded trans-acting activator of transcription (Tat) peptide which also translocates cell membranes and gains intracellular mammalian cells [12, 13]. Covalently the conjugation of Tat peptide to proteins or fluorescent markers allowed these molecules to gain into the cell. A few years later, another discovery was followed when polycationic peptide of natural (VP22 and AntP) and synthetic origin (transportan) was used for the delivery of genes, proteins, small exogenous peptide, or even nanoparticles. Furthermore, it was demonstrated that small domains in these peptides are often responsible for cellular entry [14]. Thus, these translocation sequences could be shortened to a few amino acids in comparison with the first Tat peptide, without affecting cell penetration efficiency [13]. Since that time, the list of synthetic CPPs has increased sharply, and the number continues to rise (Table 1). In the last decade, another peptide was described named maurocalcine (MCa), a 33 amino acid residue peptide that has been isolated from the venom of the Tunisian chactid scorpion Scorpio maurus palmatus. It folds according to an “inhibitor cystine knot” (ICK) motif and contains three disulfide bridges connected by the following pattern: C1–C4, C2–C5, and C3– C6 [15]. MCa acts on ryanodine receptors resulting in pharmacological activation. These receptors are calcium channels located in the membrane of the endoplasmic reticulum. They control Ca2+ release from internal stores and therefore a large number of cell functions [16, 17].
Peptide | Sequence | Origin | Cargoes |
---|---|---|---|
Protein transduction domain | |||
Tat48-60 | GRKKRRQRRRPPQ | VIH-1 | ADN, peptide, PKC inhibitor |
Pénétratin | RQIKIWFQNRRMKWKK | Drosophila Antennapedia homeodomain | HSP20 phosphopeptide |
Chimeric peptides | |||
Transportan | GWTLNSAGYLLGKINLKALAALAKKIL | Galanin + Mastoparan | Protéine, PNA |
Pep-1 | KETWWETWWTEWSQPKKKRKV | Rich domain of tryptophan + spacer + domain derived from virus SV40-NLS sequence of T antigène | Enzyme |
MPG | GALFLGFLGAAGSTMGAWSQPKKKRKV | Hydrophobic motif derived from HIV-1 gp41 + linker + domain derived from virus SV40-NLS sequence of T antigène | siARN, oligo-nucléotides |
CADY | GLWRALWRLLRSLWRLLWRA | Dérived from PPTG11, variant of JTS1 fusion protéin | siARN |
Peptide models | |||
(Arg)x | (RRRRR)X | Synthetic peptide | siARN, Cyclosporine A |
MAP | KLALKLALKALKAALKA | Synthetic peptide | Natural CPPs |
Natural CPP | |||
Maurocalcine | GDCLPHLKLCKENKDCCSKKCKRRGTNIEKRCR | Scorpio maurus palmatus | Doxorubicin |
Examples of four classes of CPPs and delivered cargoes. The list of cargo is not exhaustive and given for illustration. X = 7, 8, or 9 arginine residues.
This peptide possesses vector properties when coupled to fluorescent streptavidin. This complex was shown to enter various cell types within minutes and in all cell types tested, a common feature of CPPs. A variety of mutants of MCa were then designed in order to unravel the most active residues for its pharmacological and penetration activities (Figure 1) [18, 19].
Example of origin of four CPPs: Maurocalcine, penetratin, tat, and polyarginine. Maurocalcine, penetratin, and tat are derived from natural sequences, but polyarginine was produced by de novo conception in order to obtain a good cellular penetration.
Two distinct advances were shown to be used to bind CPPs to molecular cargoes. One process is non-covalently which connect CPP to its cargoes using electrostatic interactions, such as MPG and Pep-1, amphipathic peptides carriers, which link to cargoes beyond any cross linking or chemical changes [20]. The second approach is more frequent and uses a covalent relation between the two compounds. This means has been widely used by different teams and has demonstrated positive advances, especially with TAT, penetratin, or polyarginines [21].
Various mechanisms for CPP internalization have been suggested, but the exact one is still not well known. Yet, many data approve that the energy-dependent tool (endocytosis) and the energy-independent mechanism (direct translocation) or both are involved in the cellular uptake progress [22].
For direct penetration, various mechanisms have been described: the carpet-like model (membrane destabilization) [23] and the pore formation model (barrel-stave) [24]. Positively charged CPPs interact with negatively charged membrane components like phospholipid bilayer or heparan sulfate. Such interaction is dwelling on the first stage of all of these mechanisms, followed by destabilization of the membrane and finished by crossing of the CPP on the lipid membrane.
For endocytosis transduction or cellular digestion, pinocytosis, phagocytosis, and receptor-mediated endocytosis have been reported [25, 26]. A sum-up of CPP transduction systems is shown in Figure 2. In pinocytosis, the plasma membrane absorbs solutes, while in phagocytosis it takes great particles. In clathrin-mediated endocytosis, clathrin and also caveolin, which are receptor-mediated endocytosis and cover the intracellular part of the biomembranes, possess a key role in the uptake mechanism. These protein structures are pivotal for the membrane invagination and for the construction of the vesicles after bounding the extracellular molecule to the membrane receptor. Clathrin has a great diameter in comparison with caveolin-coated vesicles and was also considered as a selective route for the translocation of compounds into cells through specific receptors on the surface of the cell [27].
CPP translocation mechanisms.
Many determinants influence the internalization process, such as the nature of CPP or the cell type, the cargo, and the experimental conditions (temperature and pH) [22].
Chemotherapy used for treatment of cancer has a lot of defects because of the toxicity of the drugs to normal healthy cells and also to resistance developed by tumor cells to the anticancer drug [28]. The major inconveniences with used cancer chemotherapy are the absence of specificity target to tumor cells and thus poor antitumor effect. The challenge in cancer therapy is to know how to deliver a drug intact to the cytosol of every cancer cell, sparing healthy cells.
It was shown that polyarginines carry cargoes that exceed 500 Da by molecular electroporation across the cell membrane which may solve part of the drug delivery problem [29]. However, the use of well-chosen linkers and anions can help target cancer cells and contribute to successful conjugation process. For example, the CXC chemokine receptor 4 (CXCR4) is overexpressed in different types of cancer, including prostate, breast, colon, and small-cell lung cancer. Snyder et al. linked the CXCR4 receptor ligand, DV3, to two transducible anticancer peptides: a p53-activating peptide (DV3-TATp53C′) and a cyclin-dependent kinase 2 antagonist peptide (DV3-TAT-RxL). Treatment of tumor cells expressing the CXCR4 receptor with either the DV3-TATp53C′ or DV3-TAT-RxL targeted peptides resulted in an enhancement of tumor cell killing compared with treatment with nontargeted parental peptides [30]. Furthermore, hypoxia-inducible factor-1 (HIF), the transcription factor central to oxygen homeostasis, is regulated via the oxygen-dependent degradation domains (ODD) of its α isoforms (HIFα). The amino- and carboxyl-terminal sequences of ODD (NODD and CODD) were fused to TAT and injected into sponges implanted subcutaneously (s.c.) in mice by William et al. They demonstrated that this injection causes a markedly accelerated local angiogenic response and induction of glucose transporter-1 gene expression, thus opening additional therapeutic avenues for ischemic diseases [31].
In some cancer cells, such as melanoma (common eye cancers in adults), p53 seems to be inhibited by overexpression of HDM2. A transducible peptide that inhibits HDM2 and Bcl-2 for their ability to induce tumor-specific apoptosis in these cells was tested [30]. In this study, it was demonstrated that the anti-Bcl-2 peptide induced apoptosis in tumor cells but also caused variable levels of toxicity in normal cells and tissues. On the contrary, the anti-HDM2 peptide induced apoptosis in tumor cells, with little effect on normal cells in a therapeutic dose range. This peptide also caused regression of retinoblastoma in rabbit eyes, with minimal damage to normal ocular tissues. They conclude that the inhibition of HDM2 may be a promising strategy for the treatment of uveal melanoma and retinoblastoma, and that strategy may be an effective technology for local delivery of anticancer therapy to the eye.
Most of the patients with sporadic renal cell carcinomas (RCCs) exhibit mutation of the Hippel-Lindau (VHL) tumor suppressor gene. Conjugation of the protein transduction domain of HIV-TAT protein to the amino acid sequence (104–123) in the beta-domain of the VHL gene product (pVHL) arrested and then reduced proliferation and invasion of 786-O renal cancer cells in vitro. Besides, daily i.p. injections with the conjugate put off and, in some cases, caused partial regression of renal tumors that were implanted in the dorsal flank of nude mice [32].
The tumor suppressor gene p16INK4A, an inhibitor of cdk3 4, is often inactivated via intragenic mutation, homozygous deletion, and methylation-associated transcriptional silencing in a large number of human cancers, mainly in pancreatic cancer. Treated animals with the p16-derived synthetic peptide coupled with the Antennapedia carrier sequence, in which we designated as Trojan p16 peptide, showed reduced AsPC-1 and BxPC-3 s.c. tumors, respectively. Thus, we conclude that Trojan p16 peptide system, a gene-oriented peptide coupled with a peptide vector, functions for experimental pancreatic cancer therapy [33].
Recently, it was shown by Sonia et al. that coupling doxorubicin (Dox) to three cell-penetrating peptides Tat, penetratin, and maurocalcine (Dox-CPPs) is a good strategy to overcome Dox resistance in MDA-MB 231 breast cancer cells and CHO cells (Figure 3) [3, 34]. We also reported that all conjugates are able to promote cell apoptosis in the breast cancer-resistant cells MDA-MB 231 at lesser concentration needed for Dox alone. Indeed, apoptosis death was shown to be correlated with ladder-internucleosomal degradation, chromatin contraction, caspase activation, Bad and Bax activation by oligomerization on the mitochondrial membrane, and liberation of cytochrome c. Despite the effective Bcl-2 overexpression in apoptosis induced by the Dox alone, such potency was shown to be insufficient in case of Dox-CPP-triggered cell apoptotic death. Otherwise, these results suggest that there are other apoptotic signaling pathways, independent of mitochondrial one, which are implicated in Dox-CPP apoptosis. Moreover, greater effectiveness of Dox when coupled to CPPs is not due only to its higher accumulation on the cells but also to the incitement of other signaling pathways. These pathways include death receptors and activation of the JNK pathway [4, 35].
Cellular internalization of Dox by MCa. MDA-MB231 cells treated with (a) RPMI, (B) Dox alone (red), and (C) Dox coupled to Dox at the same concentration (red).
Another study led by Leslie Walker et al. showed that conjugated Dox to both ELP and SynB1 prevents tumor development in mice. In fact, conjugation of Dox to SynB1-ELP was more efficient in tumor inhibition under hyperthermic condition than Dox alone, which was twofold higher. Such conception was considered hopeful peptide candidates for drug delivery [36]. The anticancer activity of Dox was also enhanced when constructed a drug delivery system by developing 25 nm gold nanospheres (GNSs) conjugated to four α-helical CPPs [37].
A thermally sensitive quantum dot that exhibits an “on-demand” cellular uptake behavior via temperature-induced “shielding/deshielding” of CPP on the surface was synthesized. Poly(N-isopropylacrylamide) (PNIPAAm) and CPP were biotinylated at their terminal ends and co-immobilized onto the surface of streptavidin-coated quantum dots (QDs-Strep) through biotin-streptavidin interaction. Namely, under a lower critical solution temperature (LCST), the hydrated PNIPAAm chains blocked CPP cellular uptake. This effect was broken down when the LCST was raised to allow CPP moieties to be exposed on the cell surface, leading to QD cellular uptake.
Additionally, the “shielding/deshielding” temperature of CPP was also used for siRNA delivery system. Biotinylated siRNA was coupled to the surface of TSQDs. Indeed, the amount of corresponding gene silencing was increased due to the surface exposure of CPP within a rising temperature above the LCST [38].
Over the last decade, a great attention has been assigned to the importance of CPP on drug transportation of bioactive molecules in various preclinical studies. In fact, novel computational basics have been made in order to develop knowledge on CPPs [39].
Previously, different researchers have developed a few in silico algorithm approaches for CPP prediction (CPPpred) and screening to facilitate throughput CPP-based research. The in silico screening/prediction methods aimed on the use of scales of chemical characteristic, such as z-descriptors [40, 41]. It is generally followed by experimental validation to make it reliable with less cost and time-consuming approach. Later on, other CPP prediction applied neural network (NN) strategies were developed and consist on introducing an N-to-1 NN. The network proceeds by a sequence of 5 to 30 amino acids in length, as input, and gives a prediction of how probably each peptide is to be cell penetrating [42]. This CPPpred offers an advantage since it was developed with repetition-reduced training and test sets.
Over the years, the commitment therapeutic importance of CPPs motivated other teams to develop the first version of CPP database, i.e., CPPsite which supports broad information on the promising use of CPPs [43]. The CPPsite manually created database of 843 experimentally described CPPs. Each consulting gives us data of the peptide involving peptide sequence, peptide name, nature of peptide, origin, chirality, uptake efficiency, subcellular localization, etc. A deep area of user-friendly tools has been integrated in this database like analyzing and browsing tools. Moreover, they have introduced other informations concerning peptide sequences such as secondary/tertiary structure and physicochemical properties of peptides.
This database version was then developed and updated as a CPPsite 2.0 and holds 1855 entries, including 1012 recent new entries [44]. The renovated version contains further data concerning chemically modified CPPs used on the in vivo model. In addition to other informations on delivered cargoes by CPPs (proteins, molecules, nanoparticles, DNA, RNA, etc.), secondary and tertiary structures of natural and chemical CPPs (including CPP with D-amino acids) were also predicted in view of their important role in the functionality of CPPs and stored in the database. Numerous tools for information browse and analysis are combined in this database and considered as a useful resource since it is compatible for all users, including smartphone and tablet.
CPP prediction sites are a promising assist to the researchers to design cell penetrating peptide, as well as making different modification and to investigate their effect on cell penetration potency [45].
The progressive and continuous application of CPPs shows that they are efficient delivery vectors. Because of the need to ameliorate the drug delivery, a great number of CPP-based applications are still drawing the attention of researchers.
In this review, the current tendency in drug delivery by CPPs is summed up. Conjugation with CPP increases cell-surface affinity and eventual cellular uptake of bioactive molecules.
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\n\nThe Open Access Publishing Fee (OAPF) is payable only after your full chapter, monograph or Compacts monograph is accepted for publication.
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\n\n*These prices do not include Value-Added Tax (VAT). Residents of European Union countries need to add VAT based on the specific rate in their country of residence. Institutions and companies registered as VAT taxable entities in their own EU member state will not pay VAT as long as provision of the VAT registration number is made during the application process. This is made possible by the EU reverse charge method.
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