This study explores accelerated internationalization among inexperienced digital entrepreneurs who lack resources such as prior experience, knowledge, and networks, which previous research regards as prerequisites for such growth. Following an in-depth qualitative research methodology, the findings reveal three theoretical mechanisms through which inexperienced entrepreneurs can make international commitment decisions with regard to the internationalization of their digital firms. The first is a novel mindset-based approach through which an entrepreneur can make an affective commitment to the international stakeholders within a digital community. Entrepreneurs do that by applying pull-based tools in digital communication to build interest among potential network contacts. The second mechanism is a means-based approach following effectuation logic resulting in an effectual form of commitment to international stakeholders in the digital community. The mechanism relies on applying push-based tools for digital communication to facilitate interactions with known network contacts. The third mechanism is continuance commitment to international business that entrepreneurs can foster over time in tandem with accumulated international experiential knowledge. This research provides an entrepreneurial decision-making model that extends effectuation theory and integrates it with extant research. The resulting holistic entrepreneurial decision-making model explains the accelerated internationalization of digital firms. Digital technologies enable entrepreneurial activity that incorporates novel technology and creates new business ventures. Consequently, there has recently been additional room for accelerated internationalization, particularly during the COVID-19 pandemic . Interestingly, the literature reviewed revealed that there is one stream of research under label entrepreneurs’ decision-making logic that covers research dealing with use of effectuation logic and networking. Moreover, there is another stream of research that can be labeled as digital entrepreneurship, which provides insights into how entrepreneurial firms can internationalize within the digital community. However, there is no mention in the literature about how entrepreneurial decision-making logic and related networking applies to digital entrepreneurship in the context of accelerated internationalization. The following sections review earlier research and draw conclusions based on those studies; we present our positioning against the identified key articles in Table Our conceptual foundation is based on a systematic literature search of the most relevant journals related to studies investigating effectuation, networking, and digital entrepreneurship. We used Reuter’s Web of Science database and EBSCOhost (multiple databases) to perform an advanced search within relevant journals publishing international entrepreneurship research, such as Entrepreneurship Theory and Practice, Journal of the Academy of Marketing Science, Journal of Business Research, Journal of Business Venturing, Journal of International Business Studies, Journal of International Entrepreneurship, Journal of Marketing, Journal of Marketing Research, Journal of World Business, Management International Review, and Small Business Economics. We considered articles published up until 2021. We searched for the keywords Experiential knowledge can only be learned through personal experience. With experiential knowledge, emphasis is placed on the change in the services the human resources can supply which arises from their activity… experience itself can never be transmitted, it produces a change – frequently a subtle change – in individuals and cannot be separated from them (p. 53).Earlier research suggests that international experiential knowledge exerts a key influence on accelerated internationalization, such that prior knowledge of foreign markets can enhance the speed with which an entrepreneurial team perceives opportunities  and international market conditions  can cause uncertainty for entrepreneurial firms expanding internationally relatively soon after their foundation , entrepreneurs may amend their perceptions of their firm’s mission, vision, or strategy. The effectuation process may also become one based more on causal decision-making. In causation, the entrepreneur focuses on the target, which involves asking what should be done using underutilized network relationships and with partners that could confer benefits  where those processes are conducted .We conducted eight interviews applying the ontological, epistemological, and methodological assumptions of our study. The interviewees had been central to Alpha’s development and included the firm’s founders, chief executive officers (CEOs), a chief technical officer (CTO), and a chief marketing officer (CMO) . Because of their self-learned skills as amateur talents in mobile-game development, they believed in themselves and wanted to show their competence (what I know). However, regarding their international experiential knowledge, the entrepreneurs lacked the resources, dense social networks, and previous international management and industry expertise to facilitate the process of establishing a new venture with an international orientation.The Alpha founders were university students whose lack of international experiential knowledge was compensated for by their favoring an effectuation approach. They had a dream of becoming global, well-respected talents in digital programming . By these means, they attracted more interest, creating a pull factor in digital networks. As a result, the young entrepreneurs were recognized as new digital talents among game developers in the mobile gaming industry network, which encouraged them to establish a new venture.In 2003, their success at new means) and instigated close collaboration with them. This effectual commitment included an investment from the Alpha side into research and development work in order to meet Beta’s expectations. The collaboration set the Alpha entrepreneurs up with a new insider position and provided access to the global digital community, which spurred the firm’s accelerated internationalization. The Alpha staff described their relationship with Beta as active and beneficial, and Beta invested considerable resources into the partnership and, thus, shared the risk of the new venture. Although Beta gave Alpha significant autonomy in the collaboration, the Alpha entrepreneurs recognized the need to become more independent in their digital entrepreneurship.Although the entrepreneurs lacked international experiential knowledge, their capabilities in mobile-game development and digital communication  facilitated access to Beta, a multinational corporation (MNC) digital games publisher, in 2004. Because Beta management had identified the entrepreneurs behind Alpha as potential partners, the young entrepreneurs made an effectual commitment to the MNC game developer ((as new means) in mobile-game development was the foundation of their self-efficacy. The perspective led to them adopting an effectual approach as a decision-making logic. Such entrepreneurial behavior enabled increasingly greater effectual commitment in global game development collaborations with several multinational corporations, and they felt able to bypass Beta, their MNC distributor. Alpha’s management created a push through digital communication  by interacting with key players in the digital community – an example of employing effectual logic. Subsequently, the Alpha entrepreneurs committed to subcontract arrangements with several direct MNC customers in the digital mobile-game industry, which led them to invest the money received from an angel investor into rebranding the firm as Alpha Ltd. Such collaborations particularly helped the Alpha entrepreneurs recognize that they needed to gain brand visibility among consumers of the digital community . To reduce the firm’s dependence on any single relationship and to pursue rapid international growth, Alpha sold its own mobile games to operators, which triggered a staff expansion in 2006.The Alpha entrepreneurs’ initial international experiential knowledge combined with the danger of overdependence and enhanced digital capability a digital artifact). The game deliberately targeted consumers globally and, in time, proved an enormous success. The innovative touch-screen technology exposed the game to new consumers in the digital mobile-game industry and was enabled by the emerging digital global marketplaces or digital platforms.Owing to the entrepreneurs’ very limited experience of building a profitable business partnership, the expansion was unsuccessful. The entrepreneurs almost lost their financial independence and the firm failed to realize its international sales forecasts. However, Alpha’s entrepreneurs learned more about the game development industry and used that knowledge to develop new and better games. The entrepreneurs’ digital capability, which now included analytical skills and a specific understanding of the global mobile-game industry, prompted the move toward a causation-based strategic decision to commercialize their first mobile game . Therefore, they targeted several franchising opportunities and quickly built partnerships with global consumer brands outside of the digital community. These new collaborations brought Alpha’s management team closer to the retail markets and pushed the firm toward new growth opportunities flowing from the expansion into highly diversified global consumer markets. The strong digital brand also led to unexpected contacts from various fields interested in associating their products with digitalization and gaming (new means).what I can do) can compensate for a lack of international experience in a new field. Alpha leveraged its strong brand to push through effectual commitments in new avenues to foster brand extension, and the entrepreneurs also formed an innovative collaboration with a world-leading global film studio. In May 2016, the computer-animated Alpha movie was released and enjoyed substantial worldwide success. This success was extremely important for the future of Alpha and its brand; it strengthened its global network position, and as a result, industry leaders sought to collaborate with Alpha. The discourses of the Alpha management informants reveal they view effectuation as an important decision-making tool that enables the firm to remain agile to exploit new digital business opportunities through innovative product development.However, the new strategy was unsuccessful and led to the fragmentation of Alpha’s businesses. The entrepreneurs’ extensive international experiential knowledge meant they recognized that their brand would deteriorate rapidly if Alpha relied only on leveraging the brand through international consumer firms. Consequently, the entrepreneurs began to explore developing a new digital business area. However, as they were unaware of the precise new direction it would take, the entrepreneurs applied a means-based approach. Having dispatched one of the entrepreneurs to the United States to explore possible avenues, the entrepreneurs used effectual networking to identify the digital movie industry as a potential area of expansion. They accordingly sought to collaborate with a leading global film studio and mutual commitments were made to develop a new movie based on the Alpha brand. The movie deal is an example of how a means-based effectuation approach  During accelerated internationalization, entrepreneurs can follow (a) an initial global mindset-based approach leading to affective commitment, or (b) an entrepreneurial means-based approach leading to effectual commitment to the stakeholders within the digital community.Whom I know) and enabled the subsequent means-based effectuation process.The empirical evidence suggests that following the effectuation process by relying on either a mindset- or a means-based approach may involve adopting new means or setting new goals. A new finding pertaining to Sarasvathy’s  model isWhat can I do.” Hence, we offer the following synthesis:In the next event, effectual decision-making resulted in the entrepreneurs acquiring new international experiential knowledge relating to the constraints of being dependent on a single partner. The situation persuaded Alpha to increase the number of partners involved in subsequent key events. This evidenced a converging cycle of constraints on the transformation of the new digital artifact that brought the firm back to adopting a means-based effectual approach and asking, “Synthesis 2: An entrepreneur that has established mutual commitment with the stakeholders within the digital community can embark on a repeated process of effectuation based on learning by following either (a) an expanding cycle of resources or (b) a converging cycle of constraints on the transformation of new digital artifacts.Recording the changes to the discourses over time enabled us to see beyond the initial choice between effectual decision-making and causal networking  partners. The new goals cycle was applied when the company realized that the strategy was depleting its brand value, forcing it to return to applying the effectuation process during its next iteration into film production. Therefore, our entrepreneurial decision-making and networking model of accelerated internationalization see Fig.  extends Synthesis 4: As internationalization advances in a digital firm and the entrepreneurs engage in causal decision-making to attain continuance commitment, they may temporarily (a) return to effectuation by following the expanding cycle of resources or (b) the converging cycle of constraints on the transformation of the new digital artifacts.The context for this study is that of entrepreneurs’ decision-making and networking within the digital community when engaging in accelerated internationalization, doing so successfully, despite lacking experiential knowledge. This phenomenon was investigated by focusing on two literature streams: entrepreneurial decision-making and digital entrepreneurship. An examination of qualitative research identified three entrepreneurial decision-making and networking paths for entrepreneurs to adopt in the course of accelerated internationalization see Fig. .This research contributes to the international entrepreneurship research field in the following ways. First, in terms of originality (Corley & Gioia, Second, this study adds scientific utility (Corley & Gioia, Third, the current research incrementally extends the international entrepreneurship research field (Corley & Gioia, Following Corley and Gioia , our finMoreover, the entrepreneurial decision-making model for accelerated internationalization presented in our research could prove very useful in entrepreneurial education, particularly as there is a strong demand across society to promote digital entrepreneurship, as evident, for instance, in universities being expected to produce more science-based entrepreneurs, but there being few initiatives to ensure those often inexperienced graduates can select the most viable path to follow in their internationalization.


BackgroundRenal transplantation is the optimal treatment for patients of all ages with end-stage kidney disease. The long-term outcomes of renal transplantation are assessed by graft and patient survival rates. These outcomes are, in turn, influenced by post-transplant events such as delayed graft function, rejections, post-transplant infections, and post-transplant diabetes mellitus (PTDM). Each of these short-term outcomes is, in turn, determined by the interplay of various factors in the pre-, peri-, and post-transplant period. This prospective study was designed to understand the factors affecting short-term outcomes in living donor transplantation and their effect on graft and patient survival.MethodologyA total of 86 patients underwent live donor renal transplantation between January 1, 2015, and March 31, 2016, at a tertiary care hospital in north India. Of these, five were lost to follow-up, and the remaining 81 patients were prospectively followed up to December 31, 2017.ResultsThe majority of the recipients were males (91%) and the donors were females (74%). Spousal and related donors comprised 49% and 51% of donations, respectively. The mean estimated glomerular filtration rate (eGFR) of donors was 98 ± 9.2 mL/minute/1.73m². Induction therapy with basiliximab was given to 21/81 (26%) recipients. The majority of recipients  received triple-drug immunosuppression with prednisolone, tacrolimus, and mycophenolate mofetil. Delayed graft function (DGF) occurred in 4/81 (4.9%) cases. Biopsy-proven acute rejections (BPARs) occurred in 15/81 (18.5%) cases, two-thirds of which were acute antibody-mediated rejections (ABMRs). During the follow-up period, 50 episodes of infections occurred in 35/81 (43.2%) recipients, with the most common being urinary tract infection . PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of transplant. On multivariate logistic regression analysis, the most significant predictor of DGF was acute rejections and vice versa. Acute rejections also predicted the occurrence of post-transplant infections. Pre-transplant hepatitis C virus (HCV) infection and cyclosporine-based therapy were significant predictors of PTDM. At the six-month follow-up, 10/81 (12.3%) patients developed graft dysfunction. The predictors of graft dysfunction at six months were recipients of related donors and rural patients. One-year graft survival, death-censored graft survival, and patient survival rates were 85.2%, 92.6%, and 91.3%, respectively. The most common cause of death was post-transplant infections  of which the majority  were fungal infections. On multivariate logistic regression analysis, the most significant predictor of graft loss and patient loss was low pre-transplant donor eGFR and PTDM, respectively.ConclusionsGraft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors during the pre-transplant  and the post-transplant  period. Short-term outcomes of renal transplants have improved because of a better understanding of transplant immunology, more effective and safer immunosuppressants, and improvisations of surgical techniques. Most of the data on the risk factors determining transplant outcomes were based on terminal events such as graft loss and patient loss which were mainly derived from retrospective studies done before 2010 . These hStudy design and populationThis prospective observational study was conducted in the Department of Nephrology at a tertiary care hospital in north India between January 1, 2015, and December 31, 2017. All patients undergoing live donor renal transplantation between January 1, 2015, and March 31, 2016, were included. The study was cleared by the Institutional Ethics Committee on Human Research and approved by the Dayanand Medical College and Hospital (DM_216/589). The study complied with the Declaration of Helsinki of 1975, as revised in 2000. Informed written consent was obtained from all patients.Baseline assessments and treatmentDetailed history and investigations into the etiology of renal disease, age, sex, duration of dialysis, body mass index (BMI), relationship with the donor, induction therapy, hepatitis B surface antigen (HbsAg), anti-hepatitis C virus (anti-HCV) antibody, anti-human immunodeficiency virus (anti-HIV) antibody, type of immunosuppressive therapy given, and urological, vascular, and infective complications were noted. High immunological risk renal transplants (those with complement-dependent cytotoxicity (CDC), flow cytometry crossmatch positivity, or recipients positive for donor-specific antibodies (DSA)) are not routinely done at our center and were excluded from this study. Induction therapy was offered to all recipients (low risk); however, due to financial constraints, only one-quarter of recipients received non-depleting interleukin 2 receptor blocker (IL2B), intravenous basiliximab 20 mg on the day of the transplant and on day four post-transplant. All patients were initiated on triple-drug immunosuppression  in therapeutic doses which were adjusted based on trough levels. Mycophenolate was replaced by azathioprine in 9/81 (11%) recipients due to gastrointestinal intolerance (5/9) and persistent leucopenia (2/9). Tacrolimus was changed to cyclosporine in 6/81 (7.4%) recipients due to inadequate trough levels (5/6) and neurotoxicity (1/6). All recipients received three months of oral cotrimoxazole and valganciclovir prophylaxis.Follow-up procedures and study outcomesRegular check-ups of renal allograft recipients were done weekly in the first month and monthly for one year, and any complications noted were recorded and treated. All cases of biopsy-proven acute rejections (BPARs) were classified as per the 2019 modified Banff classification . ProtocoStatistical analysisStatistical analysis was done by SPSS version 25 . Categorical data were presented as percentages and quantitative data as mean ± standard deviation (SD) or median (range). Comparison of different groups was carried out using the chi-square test or Fisher exact test for categorical variables and independent Student’s t-test for comparing means of continuous variables. Multivariate logistic regression analysis was used to identify the predictors of various short-term outcomes. Survival analysis for time to graft loss and time to patient loss was done using the Kaplan-Meier test using the log-rank test for comparison between groups. Statistical significance was assumed at p-values of <0.05.Baseline donor and recipient characteristics are listed in Table Escherichia coli (60.9%), followed by Klebsiella (21.7%) and Enterobacter (17.4%). PTDM was diagnosed in 22/81 (27.2%) patients beyond six weeks of the transplant. Of these, 5/22 (22.7%) had chronic HCV infection in the pre-transplant period.Infectious and non-Infectious complications post-transplant are presented in Table Significant predictors of short-term outcomes are listed in Table Spousal versus related donors are presented in Table The salient findings of our prospective observational study of short-term outcomes of live related (60%) and spousal (40%) renal allograft recipients were one-year graft survival, death-censored graft survival, and patient survival rates of 85.2%, 92.6%, and 91.3%, respectively. This is comparable to most other single-center studies as well as large registry data -9  nephrotoxicity .In our study, donor and recipient age were not significant predictors of graft and patient outcomes on multivariate analysis. However, advanced donor age is associated with poor graft survival in large retrospective series -3. The pThe most significant predictor of graft loss on multivariate analysis was low pre-transplant donor eGFR (p = 0.046). This was similar to the findings of Norden et al. who reported that death-censored graft survival was significantly lower in grafts from donors with GFR less than 80 mL/minute with a relative risk of graft loss of 2.28 . In a reIn our study, PTDM was the most significant predictor of mortality on multivariate analysis (p = 0.020). PTDM is a risk factor for both cardiovascular diseases (CVD) and infections, which are the two most common causes of mortality in transplant settings. Using data from the USRDS database, Kasiske et al. also demonstrated that PTDM was associated with an increased risk of graft loss (hazard ratio (HR) = 1.46) and mortality (HR = 1.87) . Pre-traThe two most significant predictors of graft dysfunction at six months were rural patients and recipients of related transplants. Almost half of our patients belonged to a rural population with agriculture the main livelihood. We observed that patients of rural populations had a higher incidence of BPARs (p = 0.057) and graft dysfunction at six months (p = 0.040). Non-compliance to medications might be the reason for the adverse graft outcomes. Mittal et al. reported higher rates of BPARs and graft dysfunction among related donors compared to spousal donors in a study involving 323 living donor transplants . The autNon-use of induction therapy is a cost-saving strategy used by many centers in developing countries . In a raDGF is reported in 5-10% of living donor kidney transplants (4.9% in our study) . DGF wasUTIs are frequent after kidney transplantation but the impact on short-term outcomes is not well established. In a study by Bodro et al. in 867 kidney transplant recipients, the incidence of UTI and acute graft pyelonephritis was 21% and 15%, respectively. Although uncomplicated UTI was not associated with graft impairment, the development of at least one episode of acute graft pyelonephritis was associated with graft loss at one year . One-thiThe prospective longitudinal follow-up over one year after living donor kidney transplantation and a holistic approach to include predictors of all clinically relevant outcomes are the strengths of our study. However, our study is not without limitations. HLA typing and donor-specific antibodies (DSAs) were done pre-transplant in only a minority of patients in view of financial constraints. However, in the era of potent immunosuppressants, the role of HLA mismatches on graft outcomes is controversial . With a The results of this prospective observational study of short-term outcomes in living donor transplantation of 81 consecutive cases over a one-year period have shown one-year graft survival, death-censored graft survival, and patient survival of 85.2%, 92.6%, and 91.3%, respectively. Graft and patient survival in living donor kidney transplantation are influenced by a multitude of interdependent factors in the pre-transplant  and the post-transplant  period.


SUS gene family, SUS3 was the most highly expressed isoform in guard cells. The Arabidopsis sus3 mutant displayed changes in guard cell starch contents comparable to the Wild Type (WT) up until 6 h into the day. After this time point, sus3 guard cells surprisingly started to accumulate starch at very high rates, reaching the end of the day with significantly more starch than WT. Based on the phenotype of the sus3 mutant, we suggest that in guard cells, SUS3 is involved in the regulation of carbon fluxes towards starch synthesis during the second half of the day. SUS3 may be part of a previously predicted guard cell futile cycle of metabolic reactions, in which sucrose is re-synthesized from UDP-glucose to avoid excessive starch synthesis toward the end of the day. This is in contrast to typical storage organs, in which cytosolic SUS is required to produce ADP-glucose for starch synthesis.Starch in the stomatal guard cells is largely synthesized using carbon precursors originating from sugars imported from the leaf mesophyll. Such heterotrophic nature of guard cell starch synthesis prompted us to investigate the role of cytosolic sucrose synthases (SUS) in this pathway. Out of the six members of the Arabidopsis  Stomata are bordered by specialized guard cells, which modulate the opening and closing of the stomatal pore through changes in their turgor pressure. Starch turnover in the guard cells is critically important for stomatal movements. Within the first hour of light, starch is degraded to promote rapid stomatal opening.2 Starch is then resynthesized during the rest of day, in coincidence with stomatal closing.2 Upon plant exposure to high CO2 concentrations, starch accumulation is required for efficient stomatal closure.3 For a long time, it has been hypothesized that organic osmolytes, such as sucrose and malate, are released from starch turnover during stomatal movements to contribute to the changes in guard cell turgor.5 More recent research revealed that starch turnover yields glucose to maintain the cytosolic sugar pool as a readily available source of osmolytes, energy and signaling molecules to drive fast stomatal movements.1Stomata are microscopic pores on the leaf surface operating as gateways for CO2 is assimilated mainly via phosphoenolpyruvate carboxylase, and mitochondria are the main source of ATP.7 The heterotrophic nature of guard cells is also reflected in the way they form starch. At the beginning of the day, when stomata are fully open, guard cell photosynthesis provides some precursors to fuel the plastidial phosphoglucose isomerase-phosphoglucose mutase reactions.8 The remainder of carbon precursors derives from sugars imported from the mesophyll via the plasma membrane sugar transport proteins 1 and 4.9et al., 1992; Zrenner et al., 1995; Déjardin et al., 1997,12). SUS was previously implicated in the regulation of stomatal conductance when overexpressed in the guard cells of tobacco plants,14 but its role in guard cell starch metabolism is unknown.One additional component of such uncanonical guard cell starch synthesis pathway may be the sucrose synthases (SUS). SUS are cytosolic, plasmamembrane- or cytoskeleton-associated enzymes, catalyzing the reversible cleavage of sucrose in UDP/ADP-glucose and fructose. In storage organs, such as potato tubers, maize kernels, or pea embryos, SUS hydrolytic activity controls sink strength by providing ADP-glucose for starch synthesis , SUS is a small gene family of six members, with each isoform generally showing a distinct expression profile, depending on the plant tissue, the developmental stage or the environmental conditions.16 We performed in silico gene expression analyses using the microarray data from Yang et al.,18,19 In line with previous transcriptomic studies,21 we found that SUS3 was the isoform most highly and preferentially expressed in guard cells, followed by SUS1  and Inward-rectifying K+ channel 1 (KAT1). The expression of BAM3; a leaf marker) was downregulated in guard cells, confirming the purity of the extracted guard cell-enriched epidermal peel samples. Based on the gene expression profile, we selected SUS3 for further investigations.In Arabidopsis  and examined changes in stomatal starch levels during the light phase (under a 12-h/12-h light/dark photoperiod). The sus3 mutant displayed guard cell starch turnover comparable to the wild type (WT) up until 3 h of light, starting with similar amounts of starch at the end of the night (EoN) (sus3 mutant (We obtained a homozygous Arabidopsis T-DNA insertion line at the ht (EoN) . Consist3 mutant .Figure sus3 guard cells compared to WT (sus3 mutant leads to the conclusion that most of SUS end-products are further metabolized to fuel ATP production via the tricarboxylic acid (TCA) cycle and oxidative phosphorylation in mitochondria, as previously suggested.14Between 3 and 6 h of light, however, starch accumulation was slightly, but significantly reduced in ed to WT . This sued to WT . In any sus3 guard cells surprisingly started to accumulate starch at very high rates (22 In the light of these observations, it is likely that the over accumulation of starch in sus3 guard cells results from the disruption of the sucrose futile cycle and subsequent redirection to starch of intermediate metabolites, such as G1P, via the activity of the plastidial G1PT transporters (1Later during the day, between 6 h and 9 h of light, gh rates , reachingh rates . This ungh rates . The sucsporters .1To conclude, our study suggests that SUS3 represents a central node in the guard cell metabolism network, particularly towards the end of the day, when the guard cells have abundant amounts of sugars. By controlling the flux of carbon toward starch synthesis, SUS3 coordinates the need of energy with the removal of metabolites during stomatal closure at the end of the day. Future efforts should consider modulating SUS3 activity in guard cells to optimize stomatal movements and potentially increase plant water use efficiency and productivity.


Moreover, the orthosis significantly restored the range of motion and improved the performance of daily activities. The proposed spatial stiffness distribution can suggest a design solution to make strengthful hand orthoses with reduced weight.Stroke survivors having limited finger coordination require an active hand orthosis to assist them with grasping tasks for daily activities. The orthosis should be portable for constant use; however, portability imposes constraints on the number, size, and weight of the actuators, which increase the difficulty of the design process. Therefore, a tradeoff exists between portability and the assistive force. In this study, a personalized spatial stiffness distribution design is presented for a portable and strengthful hand orthosis. The spatial stiffness distribution of the orthosis was optimized based on measurements of individual hand parameters to satisfy the functional requirements of achieving sufficient grip aperture in the pre-grasping phase and minimal assistive force in the grasping phase. Ten stroke survivors were recruited to evaluate the system. Sufficient grip aperture and high grip strength-to-weight ratio were achieved by the orthosis  Stroke is a cerebrovascular event that occurs in 13 million people worldwide every year . Often, For stroke survivors, the limited finger coordination because of spasticity and muscle weakness is the primary obstacle for performing grasping tasks with the affected hand . In partMany types of hand orthoses have been developed. Most existing hand orthoses include multiple actuators to assist dexterous finger movements for rehabilitation purposes. The hand orthoses comprise exoskeletons , tendon-Several portable hand orthoses have been developed by reducing the number of actuators in the soft orthoses for assistive purposes in daily living ; 2020. SAn elastic structure can be used for portable orthoses  to ensurThis study presents a personalized spatial stiffness distribution design for a portable and strengthful hand orthosis to assist with grasping tasks . The spa1) Portability: The orthosis including the actuators should weigh <500 g  because 2) Grasping assistance: The orthosis should assist with the bidirectional movement of the fingers to aid with grasping tasks. The target grip aperture and minimal required grip strength are set to 80 mm (>70 mm ) and 15 3) Comfort and safety: The orthosis should not induce pain, hyperextension, and skin damage during use. The application of a compressive force to finger joints must be avoided when it is assisting with finger movement.The specifications of the orthosis made by the spatial stiffness distribution design are determined as follows based on the results of previous studies and interviews with clinicians.The number of grasp types that the orthosis can assist with is limited because the underactuation of the orthosis is inevitable for portability. Because tripod grasp achieved by three fingers  was similar with the grasping posture achieved by one of the postural synergies required for a tool use , it was T) for grasping. The passive elastic structure excluding the beam is designed as per the hand geometry of each user for comfort. Because of finger contracture in the affected hand, a 3D scanner  is used to scan the unaffected hand when the user grasps an 80-mm-diameter cylinder. The affected hand geometry is generated by mirroring the 3D scanning results assuming symmetry of the hands (The orthosis comprises a passive elastic structure (including a beam) fabricated from thermoplastic polyurethane , an intention detection module, and a control module . The orthe hands . The thuf) can sense the flexion force of the affected hand, and the FSR on the thumb module (FSRg) can measure how much grip strength is applied to a grasped object.The control module comprises a small motor  that exceeds the pre-set values . In the initial state, the fingers are passively extended (open-hand posture) at the initial angle of the motor, which is set when the cable is completely untwisted. Active flexion of the beam is initiated once the user applies a force that exceeds Thresholdgrasp. The active flexion is driven by rotating the motor to twist the cable under a nominal step input current. The motor rotates until the angle limit, which is set to when the end of the beam makes contact with the thumb module. Once the rotation angle reaches the angle limit, a proportional–integral–derivative (PID) controller maintains the angle limit for safety. When the grip strength (Fg) reaches 15 N  caused by physical perturbation, the user must reapply a force to return their hand to the desired posture.The grasping and releasing tasks are initiated when the user applies a flexion force  and two hard regions (Hard1 and Hard2)  for all users. The position of Soft2 was determined by considering the slip occurrence between the beam and fingers during MCP flexion. The beam slips with respect to the fingers  of the slip distance (Lslip) and radius of the PIP joint (rp). Because 35° of MCP flexion has been reported to occur during tripod grasping  . Becauseard2) . The pro fingers  during Mgrasping , LconsA  and two hard regions (Hard1 and Hard2) at predefined locations to allow bidirectional finger movement.A  is the lconst2 . Thus, tSoft1 and Soft2 is determined by design variables  are determined as per the measured anthropometric dimensions of an individual hand. In particular, L1, L2, and L3 are the lengths between the PPC and PDC, PDC and PIP, and PIP and DIP, respectively. W is the width of the index and middle fingers. H is the thickness of the hard regions. To ensure high stiffness in the hard regions and the applicability of the Euler–Bernoulli theory, H is set so that the aspect ratio of the entire beam slightly exceeds 10. As geometric constraints, the distal edge of Soft1 should be more proximal than PDC (L1), and the distal edge of Soft2 should be more proximal than PIP joint (L2). The routing structures are positioned along the PPC, PDC, and PIP joint to deflect each of Soft1 and Soft2 under the assistive force.The stiffness can be adjusted by changing the thickness along the beam . The stiThere exists a tradeoff between an achievable grip aperture and grip strength because an increase in the spatial stiffness leads to an increase in the grip aperture and required assistive force for grasping. The stiffness optimization enables the orthosis to achieve a target grip aperture in the pre-grasping phase while minimizing the required assistive force in the grasping phase. It would enable the orthosis to grasp common objects with increased grip strength by a given small-sized motor. Because stroke survivors have different joint characteristics  such as Soft1 and Soft2, the relevant individual hand parameters should be measured. The anthropometric dimensions of the hand are the primary parameters. In this study, the dimensions were measured using a goniometer , and they are used to determine L1, L2, L3, W, and H of the beam. Because finger contracture made it difficult to measure the affected hand, the dimensions were measured for the unaffected hand assuming the symmetry of both hands (ϕMCP and ϕPIP) are the secondary parameters. The target joint angles that should be maintained are used to determine the stiffness of Soft1 and Soft2. Because the joint angles differ among individuals because of the dissimilar hand size, the joint angles should be measured for each user and then be used to set constraints in determining the stiffness of Soft1 and Soft2. The joint angles were measured using the goniometer as a user grasps an 80-mm-diameter cylinder with their unaffected hand. The force applied to the beam by the fingers  deflects Soft1 and Soft2 and decreases the grip aperture. This joint resistive force should be known to determine the necessary stiffness for Soft1 and Soft2 to achieve passive extension. Thus, the joint resistive force is the tertiary parameter. Because the joint resistive force differs depending on the degree of spasticity, it should be measured for each user.Before determining the stiffness of th hands . The joiBefore measuring the force, the location where the force is applied was obtained by static analysis under the condition that the finger and beam contact each other. In this study, finite element analysis (FEA) was used using ABAQUS  for static analysis. An individual hand–beam model was developed  that useFMCP and FPIP) for the user were measured based on the positions of primary contact areas  of the index finger to maintain fully extended PIP joint is used to measure FPIP. For this measurement, the experimenter externally holds the MCP joints in full extension. During the measurement, the force was nearly constant when the spastic response occurred right after the extension settled down. To eliminate the contribution of the spastic response immediately after movement, the force was measured for 1 min, and the average force over the last 10 s is considered as FMCP or FPIP.The joint resistive forces  and ψ2 (s2) are the beam deflection angles at s1 and s2, which are the arc lengths between the fixed end and a point on the corresponding segment (h (s1) and h (s2) are the thickness at s1 and s2. M1, M2, and E are the corresponding bending moments and Young’s modulus. The beam stiffness should be set to ensure a grip aperture of 80 mm. The difference between the beam deflection angles and joint angles at the primary contact areas is < 2.95° on average (1 and B.C2) were set to make the beam deflection angles at the primary contact areas equal to the individually measured joint angles (ϕMCP and ϕPIP). Hard1 and Hard2 were assumed to be sufficiently stiff to ensure that any changes in ψ1 (s1) and ψ2 (s2) are negligible. In this study, MATLAB  was used to calculate h1 and h2 based on λ1 and λ2, which are pre-set to change in increments of 1 mm within the geometric constraints. Then, stiffness solutions that satisfy Eq. where  segment . h  using a high-precision micromechanical test system . This measured Young’s modulus (22.35 MPa) was used as 1/s usingFMCP and FPIP) were used in Eq. The spasticity of the flexor muscles can change over time and made it difficult to guarantee that the beam, which has fixed spatial stiffness distribution, would maintain the target grip aperture. A grip aperture less than the target of 80 mm would present a challenge in positioning common objects within the hand for grasping in the pre-grasping phase. Thus, a safety factor was applied to the degree of spatial stiffness; the spatial stiffness distribution was designed to achieve the target grip aperture against maximal joint resistive forces. The joint resistive forces are greatest when the fingers are fully extended. Thus, the maximal joint resistive forces statically measured at the fully extended posture  should be determined first. The ROMs of finger joints during a tripod grasp were used to determine the required beam deflection. The ROMs were measured during tripod grasping tasks using the unaffected hand . In thisT1, T2) (Seg 1 and Seg 2) as per the position of the PDC, where the routing structure was located. The relationships were obtained for each beam segment because the assistive force in Seg 2 does not generate a moment in Seg 1. For the simulation, the assistive force was applied at the positions of the routing structures, and the beam segments were meshed with C3D20 elements and subjected to the dynamic flexural modulus (46.49 MPa). Plastic deformation resulting from active flexion was not considered because the plastic strain was expected to be small owing to the thinness of the beam.In this study, FEA was used to simulate the active flexion of stiffness solutions to obtain the relationship between beam deflection angles  . The beaT1 and T2. In particular, T1 and T2 that yield T1 and T2 were then used to identify the optimal solution that required the minimal assistive force among the stiffness solutions , and finger joint angles when the finger makes contact with the beam were calculated. It was confirmed that the PIP joint angle increased linearly with respect to the MCP joint angle, and this inter-joint coordination pattern of the joint angles was obtained to check whether finger joint angles of users increase in accordance with the obtained inter-joint coordination pattern during assistance.The finger joint angles during active flexion were obtained using an individual hand–beam model. For the model, the optimal solution was used for the beam, and measured dimensions were used for the hand . The beaTen stroke survivors having varying degrees of spasticity were recruited  to evalu1) Beam deflection and grip aperture: The beam deflection was measured to confirm whether it was equal to the target deflection. The target deflection was obtained using FEA by applying the maximal joint resistive force to the beam having the measured Young’s modulus. The increase in the deflection of the distal end of the beam was used  to deter2) ROM measurement: The ROMs for the MCP and PIP joints of the index finger were measured before and after the orthosis was applied to the affected hand. Reflective markers were placed atop the metacarpal, MCP, PIP, and DIP joints and the fingertip of the index finger for tracking, and joint angles were obtained based on the 3D trajectory data of the markers. The voluntary ROM  was obtained, where θvoluntary and θassisted are the maximal unassisted and assisted extension angles, respectively.3) Grasp performance: The maximum grip strength with the orthosis, in addition to the ability of the orthosis to grasp various objects, were evaluated. The objects applied for this test were selected based on the previous study , and the4) Functional assessment and questionnaire: Each participant was instructed to perform nine ADL tasks from the Chedoke Arm and Hand Activity Inventory (CAHAI)-9  to evaluThe following criteria were used to evaluate the performance of the proposed orthosis design.The beam deflection was less than the target deflection, thereby yielding a grip aperture larger than the target grip aperture of 80 mm. The distal end of the beam deflected by 12.17 ± 10.00 mm immediately after donning, generating the grip aperture of 94.26 ± 10.73 mm. This measured deflection was less than the target deflection of 40.08 ± 7.37 mm primarily owing to viscosity of the TPU. Because of creep occurred after donning and plastic deformation by active flexion, the beam deflection increased by 9.38 ± 5.48 mm after four repetitions of active flexion, which corresponded to an average decrease of 6.74 mm for the grip aperture. Non-etheless, the measured beam deflection of 21.54 ± 9.36 mm still did not equal to the target deflection of 40.08 ± 7.37 mm, yielding a grip aperture of 87.52 ± 6.40 mm. The error for the beam deflection would be because of the safety factor considered in designing the stiffness of the beam. The beam stiffness was set to yield the target grip aperture against the maximal joint resistive force; however, fingers would apply force less than the maximal joint resistive force on the beam. This would primarily make the measured deflection be less than the target deflection, which led to increase in the grip aperture.The orthosis effectively assisted the finger joints for all participants . All parThe finger joint angles increase in accordance with the inter-joint coordination pattern obtained by the individual hand–beam model. The “Measured joint angles” in All participants could grasp each object with the orthosis. Furthermore, they were able to establish contact between their fingertips and large-size objects . However, the large slip between the fingers and beam prevented the fingertips from contacting the small-size objects . The maximum grip strength was measured as 26.27 ± 3.90 N, and the orthosis showed a high grip strength-to-weight ratio .The results of the CAHAI-9 tasks  demonstrThe participants answered that the device is sufficiently lightweight (score: 4.3 ± 0.7) and comfortable (score: 4.2 ± 0.5). Moreover, they were satisfied with the assistance of the orthosis (score: 4.3 ± 0.48).In this study, a personalized spatial stiffness distribution is presented for a portable and strengthful hand orthosis. The stiffness was optimized for each participant based on measurement of individual hand parameter to satisfy predetermined requirements for the orthosis: maintaining a minimum grip aperture of 80 mm and minimizing the assistive force needed to achieve flexion. The stiffness optimization of the passive elastic structure assists individuals with finger flexor spasticity to achieve the target grip aperture to grasp common objects while minimizing the antagonistic assistive force to generate sufficient grip strength. The experimental results demonstrated that the orthosis achieves a high grip strength-to-weight ratio and weighs only 454 g, including all of the motor, electronics, and battery located at the hand and forearm. It was demonstrated that the strengthful all-in-one orthosis achieved by the spatial stiffness distribution design can assist participants with the bidirectional movement of the affected hand to grasp various objects and thus can aid with bimanual tasks for ADL.The passive elastic structure enabled spastic finger joints to be extended even for a participant who has MAS grade of three. Previous orthoses  assist wThe spatial stiffness distribution design of the orthosis significantly affects ROMs of finger joints during assistance. In this study, by adjusting the stiffness along the beam considering the slip between the fingers and beam, the limited increase in ROM during assistance is avoided. In particular, the hard region of beam can limit the ROM of the PIP joint when the slip during finger flexion is not considered in the spatial stiffness distribution design. The soft regions were respectively positioned close to the finger joints considering the slip, and their stiffness were adjusted to emulate the tripod grasp. The proposed design prevents the beam from blocking finger flexion and enables users to conduct tripod grasp. The proposed orthosis was demonstrated to increase the ROM of finger joints by an average of 31.7°, which is similar to that of a previous orthosis  .The results highlight the importance of a user-specific orthosis design. To maximize user compliance and increase grip strength through reduced actuator size and weight, orthosis was personalized for each participant based on the measurements of hand parameters. This was achieved by first considering the individual hand geometry. With the exception of the beam component, the passive elastic structure was designed based on the affected hand geometry generated by 3D scanning. All participants reported that the orthosis was comfortable. The second individualized characteristic that was considered was the joint resistive force, particularly for MCP and PIP joints. The spatial stiffness distribution was personalized based on measurement results of joint resistive force to ensure sufficient grip aperture and high enough grip strength, and it was shown that the orthosis can achieve grasping assistance with a high grip strength-to-weight ratio. The required motor size and weight for grasping assistance would be reduced by considering individual joint characteristics in the spatial stiffness distribution design.The TSA mechanism was selected to improve the portability of the orthosis using its high contraction force-to-torque ratio and mechanical simplicity. Owing to its characteristics, the actuating module adopting the TSA mechanism becomes compact in comparison with the other actuating modules such as soft fluidic actuators . HoweverThe proposed orthosis does have limitations. First, the cable of the TSA mechanism can break during use. The cable breaks after being twisted several times , which mIn this study, a personalized spatial stiffness distribution design is presented for a portable and strengthful hand orthosis to assist with grasping tasks. The objective was to design spatial stiffness distribution that can assist bidirectional finger movement with a sufficient grip aperture in the pre-grasping phase and high enough grip strength in the grasping phase. The orthosis includes a passive elastic structure with an individually optimized stiffness and a cable contracted by TSA mechanism using a single motor. In the experiment, the orthosis can assist with grasping tasks for ADL by providing a sufficient grip aperture and grip strength. The orthosis increased the grip aperture and grip strength of all participants, enabling successful grasping even by those with severe degrees of spasticity.


Based on the theory of sway frame column, the equation of the effective length factor was derived in this paper. Combined with the characteristics of semi-rigid joints, the linear stiffness correction factor of horizontal bar was introduced, and the equation of effective length correction factor was obtained. By using MATLAB programming method, the three-dimensional relationship between the effective length correction factor and the influencing factors was obtained, and the entire process of the stability bearing capacity of the disc-buckle type high support system was described in detail, which improves the stability calculation theory of the high support system. The influence of setting parameters, joint bending stiffness, geometrical size, and material properties on the effective length correction factor is studied. Simultaneously, the joint bending stiffness of semi-rigid joints is determined. The area of the effective length correction factor is analyzed to optimize the design of the setting scheme using horizontal bars and vertical poles of different sizes. The results show that the lift height significantly affects the effective length correction factor during the load bearing process; the factor decreases with increasing lift height. Large transverse and longitudinal distances influence this rule during the initial load bearing. When the joint bending stiffness is less than 100 (kN·m)/rad, the effective length correction factor decreases rapidly with an increase in joint bending stiffness. When the joint bending stiffness is greater than 100 (kN·m)/rad, the effective length correction factor is unaffected by the joint bending stiffness. When the joint bending stiffness is large at initiation of loading, the effective length correction factor decreases with an increase in the outer diameter of the horizontal bar. When the joint bending stiffness is small, the effective length correction factor increases with an increase in the section size of the vertical pole. Therefore, the outer diameter of the horizontal bar significantly affects the effective length correction factor, and a larger diameter is more conducive to the overall stability. Furthermore, the elastic modulus effects the effective length correction factor for the unstable support system. With increasing complexity of the building functional requirements, large spatial structure forms continue to emerge. However, the diversification of spatial structure forms has brought technical problems to construction. New requirements for the safety and stable construction of high support system need to be put forward. Disc-buckle type steel scaffolding has been widely used in construction. However, due to the imperfect stability calculation theory of high support systems and excessive dependence on experienced formulation of the construction scheme, safety accidents occur frequently. The method for the stability calculation of formwork support has been given in the “Technical specification for safety of disk lock steel tubular scaffold in construction”  and “StaMAB = (EIc2/lc2)[CθA + SθB − (C + S)ρ2] and MAG = (EIc1/lc1)[CθA + SθB − (C + S)ρ1], where ρ1 = ρ2, and MAC = 6(EIb1/lb1)θA, MAD = 6(EIb2/lb2)θA.The moment of force of the horizontal bar and vertical pole ends related to joint A are established as MA = 0, that is, MAB + MAG + MAC + MAD = 0 and The equilibrium equation of joint A is established as ∑K1 was introduced. It is defined as the sum of linear stiffness of the horizontal bar connected to the upper end of the AB vertical pole to the linear stiffness of the vertical pole. Thus, CθA + SθB − (C + S)ρ2 + 6K1θA = 0. Reorganizing the results, we obtain The ratio K2 related to the lower end constraint of AB vertical pole.Similarly, the moment equilibrium equation of joint B can be established and MBA = (EIc2/lc2)[CθB + SθA − (C + S)ρ2] and MBH = (EIc3/lc3)[CθB + SθA − (C + S)ρ3], where ρ2 = ρ3, and MBE = 6(EIb3/lb3)θB and MBF = 6(EIb4/lb4)θB. Subsequently, the equilibrium equation of joint B is established as ∑MB = 0, that is, MBH + MBA + MBE + MBF = 0, and First, torques of horizontal bars and vertical poles end related to joint B are established as K2 of the sum of the linear stiffness of the horizontal bar connected to the lower end of the AB vertical pole to the linear stiffness of the vertical pole was introduced, and CθB + SθA − (C + S)ρ2 + 6K2θB = 0. Reorganizing the results, we obtain The ratio MAB + MBA + PΔ = 0, where Δ = ρ2lc2 and P = k2EIc2. Furthermore, PΔ = k2EIc2ρ2lc2 = (EIc2/lc2)(klc2)2ρ2 and (EIc2/lc2)[CθA + SθB − (C + S)ρ2] + (EIc2/lc2)[CθB + SθA − (C + S)ρ2] + (EIc2/lc2)(klc2)2ρ2 = 0.To establish the equilibrium equation of the vertical pole itself, Reorganizing results in Adding Eqs Subsequently, From the linear Eqs C and S are substituted and expressed by μ = π/klc2, after which the buckling The trigonometric functions of μ of laterally shifted multi-story and multi-span rigid frame columns, which depends on the constraint parameters K1 and K2 Additionally, the value of μ can be determined by the following practical calculation GB 50017–2017 Appendix E.0.2 gives the effective length factor R, which is obtained by the semi-rigid stiffness curve, and the rotation angle of the double curvature bar end is θA = θD and MAD = MDA. By substituting these into Eqs lb denotes the transverse and longitudinal distance; R denotes joint bending stiffness; Ib denotes the cross sectional moment of inertia of horizontal bar; and E denotes the elastic modulus of horizontal bar.Let the joint bending stiffness be α of horizontal bar can be obtained from The linear stiffness correction factor μmod is obtained, as shown in μmod denotes the effective length correction factor; K1 denotes the ratio of the sum of horizontal bar linear stiffness of the upper end of vertical pole to the vertical pole linear stiffness, K2 denotes the ratio of the sum of horizontal bar linear stiffness of the lower end of vertical pole to the vertical pole linear stiffness, α denotes the linear stiffness correction factor of horizontal bar, Then, the effective length correction factor According to Appendix A of the Technical specification for safety of disk lock steel tubular scaffold in construction JGJ231-2010 [K1 = K2 = k, lb1 = lb2 = lb3 = lb4 = lb, lc1 = lc2 = lc3 = lc4 = lc, Ib1 = Ib2 = Ib3 = Ib4 = Ib, Ic1 = Ic2 = Ic3 = Ic4 = Ic.In high support system, the lift height and transverse and longitudinal distance are generally set in the same setting scheme; furthermore, the specifications of the horizontal bar and vertical pole are fixed. Therefore, in general, K = αk and Hence, μmod is related to three variables.From K, described as follows.There are four primary conditions for the value of E = 2.06 × 108kN/m2 and IbA = 9.28 × 10−8m4; the vertical pole adopts the model of A-LG, E = 2.06 × 108kN/m2 and IcA = 23.10 × 10−8m4. Therefore, Condition 1: the horizontal bar adopts the model of A-SG, E = 2.06 × 108kN/m2 and IbA = 9.28 × 10−8m4; the vertical pole adopts the model of B-LG, E = 2.06 × 108kN/m2 and IcB = 11.36 × 10−8m4. Therefore, Condition 2: the horizontal bar adopts the model of A-SG, E = 2.06 × 108kN/m2 and IbB = 6.07 × 10−8m4; the vertical pole adopts the model of A-LG, E = 2.06 × 108kN/m2 and IcA = 23.10 × 10−8m4. Therefore, Condition 3: the horizontal bar adopts the model of B-SG, E = 2.06 × 108kN/m2 and IbB = 6.07 × 10−8m4; the vertical pole adopts model of B-LG, E = 2.06 × 108kN/m2 and IcB = 11.36 × 10−8m4. Therefore, Finally, condition 4: the horizontal bar adopts the model of B-SG, The connection joints of the disc-buckle type formwork support comprised the disk-plate welded to the vertical pole, wedge head welded to the horizontal bar, and the wedge inserted into the wedge head welded to the end of the diagonal bracing, as shown in The geometrical size of the connection joints used at the construction site is shown in L3 of the wedge insertion in the disk-plate, the thickness of the wedge b and the disk-plate tP. The wedge insertion state of the positive- and negative-directions are shown in All components were obtained from the construction site. Due to the nonstandard production and recycling, the dimensions of components differed, which resulted in different configurations of each experimental joint. The specific differences are shown in the depth The joint bending state consists of positive- and negative-direction bendings, represented by “P” and “N,” respectively, in the study. Eight groups of parallel experiments were carried out to study the effects of the positive- and negative-direction bending.The experimental device is shown in The loading mechanism was controlled by force and the process included preloading, formal loading, and unloading. Each specimen was preloaded to approximately 20% of the yield load to verify whether the experimental device and measurement equipment were operating normally. Each loading stage was 1/10-1/15 of the estimated ultimate load and the load remained in each step for 2 min. When the horizontal bar had a large angle relative to the vertical pole and the load was no longer increased, the displacement increased gradually. This was considered as the specimen of joints reaching the ultimate failure state. The formal experimental loading mechanism is listed in Five displacement transducers with measurement accuracy of 0.01 mm were used to measure the displacement of the horizontal bar and vertical pole during loading. The upper and lower measuring points of the vertical pole were set to 150 mm from the joint center, which were recorded as measuring point 1 and 2, respectively. The displacement measuring points of the horizontal bar were set 100 mm and 200 mm away from the joint center, which were recorded as measuring point 3 and 4, respectively. The loading point of the horizontal bar was set to 300 mm away from the joint center, which was recorded as measuring point 5; this measuring point was set for the calibration data. The arrangement of the measuring points is shown in F denotes the vertically concentrated load at the loading point of the horizontal bar and L denotes the distance from the loading point to the joint center (which can be taken as 300 mm). The relative rotation angle of the joint can be obtained using 1, Δ2, Δ3, and Δ4 denotes the displacement transducer reading data at measuring points 1, 2, 3, and 4, respectively. Furthermore, d3–4 denotes the straight-line distance between the measuring points 3 and 4, d1 and d2 denotes the distances from measuring points 1 and 2 to the joint center, respectively, and θ1 denotes the rotation angle of the horizontal bar section relative to the joint. A section of the vertical pole produces a rotation angle relative to the joint, which is denoted by θ2 and expressed in Qian XJ  employedThe bending moment–rotation angle curve of the joint was obtained by processing the data obtained from the experiment through Eqs At the initial stage of loading, the specimen had no obvious deformation; the joint bending stiffness is larger when the bending moment is small . With inThe moment–rotation curves corresponding to each experiment are shown in As can be seen from As can be seen from Du RJ  providedMP denotes the full plastic bending moment of the horizontal bar; Mp = Wpx · fy, where Wpx denotes the plastic section modulus; EIb/lb denotes the linear stiffness of the horizontal bar; and Ib denotes the cross-section inertia moment of the horizontal bar.The curves in the figure were plotted using the following equations.R = 24 mm and t = 2.5 mm. According to the material test results, the yield strength of the horizontal bar was set to 401.44 × 106 Pa and the elastic modulus was set to 2.06 × 1011 Pa. Therefore, it was calculated that Wpx = 3.8648 × 10−6 m3; subsequently, it was calculated that MP = 1551.5 N·m and Mplb/EIb = 0.02436 rad.For disc-buckle type formwork support, the section size of the horizontal bar was set to The experimental data of the connection joints were processed without dimensions using the above equation  and corrRmin of the socket-type formwork support can be derived from M* = 25θ*, which results in Rmin = M/θ = 0.5EIb / lb. Additionally, the maximum initial joint bending stiffness Rmax can be derived from M* = 25θ*, which results in Rmin = M/θ = 25EIb / lb, as shown in Du RJ  summarizRmin and Rmax were related to the transverse and longitudinal distance, lb. The results of the range of initial joint bending stiffness of the horizontal bars of the two specifications are as follows.As seen from Condition 1:lb,min = 0.3m, Rmin = M/θ = 0.5EIbA / lb,min = 31.9(kN · m)/rad;when lb,max = 2.0m, Rmin = M/θ = 0.5EIbA / lb,max = 4.8(kN · m)/rad;when lb,min = 0.3m, Rmax = M/θ = 25EIbA / lb,min = 1593.1(kN · m)/rad;when lb,max = 2.0m, Rmax = M/θ = 25EIbA / lb,max = 239.0(kN · m)/rad.when When the transverse and longitudinal distance differed, the regional boundary of initial bending stiffness of the semi-rigid joint differed, as listed in Condition 2:lb,min = 0.3m, Rmin = M/θ = 0.5EIbB / lb,min = 20.8(kN · m)/rad;when lb,max = 2.0m, Rmin = M/θ = 0.5EIbB / lb,max = 3.1(kN · m)/rad;when lb,min = 0.3m, Rmax = M/θ = 25EIbB / lb,min = 1042.0(kN · m)/rad;when lb,max = 2.0m, Rmax = M/θ = 25EIbB / lb,max = 156.3(kN · m)/rad.when When the transverse and longitudinal distance differed, the regional boundary of initial bending stiffness of the semi-rigid joint differed, as listed in From Tables From this analysis, the following can be determined.Rmax = M/θ = 5EIb / lb.When the joint was in the positive bending state, the maximum initial bending stiffness was, Rmax = M/θ = 2.5EIb / lb.When the joint was in the negative bending state, the maximum initial bending stiffness was, Rmin = M/θ = 0.5EIb / lb.Regardless of whether the joint was in the positive or negative bending state, the minimum initial bending stiffness was, Models A-SG and B-LG were adopted in horizontal bars and vertical poles, respectively. The regional boundary of initial bending stiffness of semi-rigid joint at different transverse and longitudinal distances are summarized in Tables K = αk, where According to the analysis performed above, the equation of the effective length correction factor is μmod was primarily considered in the four conditions.The effective length correction factor Condition 1: model A-SG was adopted in the horizontal bar, Condition 2: model A-SG was adopted in the horizontal bar, RAP = 5 ~ 319(kN · m)/rad. When the joint was in the negative bending state, the value range of the initial bending stiffness was RAN = 5 ~ 159(kN · m)/rad.In Conditions 1 and 2, when the joint was in the positive bending state, the value range of the initial bending stiffness was Condition 3: model B-SG was adopted in the horizontal bar, Condition 4: model B-SG was adopted in the horizontal bar, RBP = 3 ~ 208(kN · m)/rad. When the joint was in the negative bending state, the value range of the initial bending stiffness was RBN = 3 ~ 104(kN · m)/rad.In Conditions 3 and 4, when the joint was in the positive bending state, the value range of the initial bending stiffness was The effective length correction factor of the aforementioned four conditions was obtained using MATLAB. When considering the influence of the effective length correction factor on the joint bending stiffness, transverse and longitudinal distance, and lift height, the three-dimensional cloud diagram of the respective relationships were obtained, as shown in The results indicate that when the overall high support system bore the initial load, the lift height had a significant influence on the effective length correction factor; this influence was more obvious when the transverse and longitudinal distance was large. Furthermore, the transverse and longitudinal distances affected the effective length correction factor when the lift height was small. When the load of the overall high support system decreased gradually, the lift height played a decisive role in the effective length correction factor and the transverse and longitudinal distances had little influence.The combined conditions between different types of horizontal bars and vertical poles are shown in Through this process, the bending moment–rotation curves of the joint were determined, and subsequently, the joint bending stiffness was obtained. After the setting parameters were determined, the effective length correction factor was calculated; note that herein, the value of the effective length correction factor was taken during the stiffness change to accurately control the process description of the overall stability bearing capacity.According to the region of the semi-rigid joint bending stiffness of the socket-type formwork support, the value area of the effective length correction factor under various conditions was determined. Figs The effective length was obtained by multiplying the effective length correction factor of the four conditions in The influence of the joint bending stiffness on the effective length correction factor when the lift height was varied is shown in R = 5~319 (kN·m)/rad in condition 1 and condition 2, so the bending stiffness of the relative dangerous condition is set to R = 150 (kN·m)/rad, and the effective length correction factor can be obtained. Similarly, the joint initial bending stiffness R = 3~208 (kN·m)/rad in condition 3 and condition 4, so the bending stiffness of the relative dangerous condition is set to R = 100 (kN·m)/rad.According to the above research, the joint initial bending stiffness ϕ42 × 3.2, ϕ52 × 3.2, ϕ48 × 2.6, ϕ48 × 3.2, and ϕ48 × 3.6.To study the influence of the section size of horizontal bar on the effective length correction factor, the outer diameter and wall thickness size of the horizontal bar were set to 48 mm ± 0.5 mm and 2.5mm ± 0.5 mm, respectively. The relevant parameters are listed in The three-dimensional relationship between the outer diameter size of the horizontal bar section and effective length correction factor when the section size of the vertical pole was varied is shown in The three-dimensional relationship between the wall thickness size of the horizontal bar section and effective length correction factor when the section size of the vertical pole was varied is shown in With increasing outer diameter and wall thickness of the horizontal bar section, the effective length correction factor exhibited a decreasing trend, but the overall effect was small. There was only an influence when the joint bending stiffness was large, the transverse and longitudinal distance was set to 2.0 m, and the lift height was set to 0.5 m. This indicates that the section size of the horizontal bar had an influence on the effective length correction factor under the initial joint bending stiffness when the transverse and longitudinal distance was large or the lift height was small in the setting parameters, and the outer diameter had a significant influence on the effective length correction factor. Essentially, the larger the section size of the horizontal bar, the smaller the effective length correction factor, and the more conducive it is to the overall stability.ϕ43 × 2.5, ϕ53 × 2.5, ϕ48 × 2.0, ϕ48 × 2.5, and ϕ48 × 3.0.To study the influence of the section size of the vertical pole on the effective length correction factor, the section size selected was relatively large; the outer diameter and wall thickness of the vertical pole were set to 48 + 0.4 mm and 48–0.6 mm, respectively. The relevant parameters are listed in The three-dimensional relationship between the outer diameter size of the vertical pole section and effective length correction factor when the section size of the horizontal bar was varied is shown in The three-dimensional relationship between the wall thickness size of the vertical pole section and effective length correction factor when the section size of the horizontal bar was varied is shown in In summary, the effective length correction factor increased with increasing section size of the vertical pole. When the joint bending stiffness was small, the influence was more obvious. Whereas, when the joint bending stiffness was large, the transverse and longitudinal distance and lift height had an influence on the relationship between the section size of the vertical pole and effective length correction factor. The outer diameter size of the vertical pole had a significant influence on the effective length correction factor with a small joint bending stiffness, and the influence degree was not affected by the size of the setting parameters.The variation of the effective length with the section size is shown in 5N/mm2, 2.00 × 105N/mm2, 2.06 × 105N/mm2, 2.10 × 105N/mm2, and 2.20 × 105N/mm2. The influence of the section size of the horizontal bar was considered when the specification of the vertical pole was set to ϕ48 × 3.2, and the section size of the horizontal bar was set to GK-1: ϕ48 × 2.5; GK-2: ϕ48 × 2.0; GK-3: ϕ48 × 3.0; GK-4: ϕ43 × 2.5; and GK-5: ϕ53 × 2.5, as summarized in ϕ48 × 2.5, and the section size of the vertical pole was set to GK-6: ϕ48 × 2.6; GK-7: ϕ48 × 3.6; GK-8: ϕ42 × 3.2; and GK-9: ϕ52 × 3.2, as summarized in The influence of elastic modulus on the effective length correction factor was studied by analyzing different sizes of the horizontal bar section and vertical pole section. Five elastic modulus parameters were considered, namely 1.90 × 10The three-dimensional relationship between the elastic modulus and effective length correction factor is shown in When the overall high support system bears the initial load, the parameters of lift height, both big or small, have a significant influence on the effective length correction factor. This influence was more obvious when the transverse and longitudinal distance was large. When the load of the overall high support system decreases gradually, the parameters of lift height play a decisive role in the effective length correction factor, and the parameters of transverse and longitudinal distance have little influence.R = 150 (kN·m)/rad, and the bending stiffness of the relative dangerous condition is set to R = 100 (kN·m)/rad. Finally, the effective length correction factor of different working conditions are obtained.When the joint bending stiffness is less than 100 (kN·m)/rad, the effective length correction factor is greatly affected by the joint bending stiffness. With increasing of joint bending stiffness, the effective length correction factor decreases rapidly and the transverse and longitudinal distance has no influence. When the joint bending stiffness is increased to greater than 100 (kN·m)/rad, the effective length correction factor remains unchanged and the transverse and longitudinal distance has a negligible influence on the effective length correction factor. The bending stiffness of the relative dangerous condition is set to When the joint bending stiffness is large, the effective length correction factor is affected primarily by the section size of the outer diameter. This influence of the wall thickness is small. The effective length correction factor decreases with increasing outer diameter size of horizontal bar. When the joint bending stiffness is small, the effective length correction factor is affected primarily by the section size of vertical pole, especially the outer diameter size. The effective length correction factor increases with increasing section size of the vertical pole. Therefore, it is known that the outer diameter size of the horizontal bar plays a decisive role in the effective length correction factor.When the joint bending stiffness is large, at the initial stage of the overall structure under loading, the outer diameter size of the horizontal bar and the vertical pole section influence the effective length and the wall thickness size of the section has little influence. A larger outer diameter size of the horizontal bar section is more conducive to the overall stability. When the joint bending stiffness is small, i.e., the overall structure is in a failure state, the section size of the vertical pole has an influence on the effective length and the section size of the horizontal bar has little influence. The effective length increases with increasing section size of the vertical pole.When the joint bending stiffness is large, the elastic modulus has no influence on the effective length correction factor. With decreasing joint bending stiffness, the elastic modulus has a proportional influence on the effective length correction factor.


These prediction tools output hundreds of potential peptide candidates which require further processing; however, these tools are either not graphical or not friendly for non-programming users. We present Epitope-Evaluator, a web tool developed in the Shiny/R framework to interactively analyze predicted T-cell epitopes. Epitope-Evaluator contains six tools providing the distribution of epitopes across a selected set of MHC alleles, the promiscuity and conservation of epitopes, and their density and location within antigens. Epitope-Evaluator requires as input the fasta file of protein sequences and the output prediction file coming out from any predictor. By choosing different cutoffs and parameters, users can produce several interactive plots and tables that can be downloaded as JPG and text files, respectively. Using Epitope-Evaluator, we found the HLA-B*40, HLA-B*27:05 and HLA-B*07:02 recognized fewer epitopes from the SARS-CoV-2 proteome than other MHC Class I alleles. We also identified shared epitopes between Delta, Omicron, and Wuhan Spike variants as well as variant-specific epitopes. In summary, Epitope-Evaluator removes the programming barrier and provides intuitive tools, allowing a straightforward interpretation and graphical representations that facilitate the selection of candidate epitopes for experimental evaluation. The web server Epitope-Evaluator is available at  T-cell epitopes are peptides derived from processed antigens that are recognized by T-cells to elicit adaptive immune responses. Generally, CD4+ T-cells recognize epitopes between 13–17 amino acidic residues presented on the surface of major histocompatibility complex (MHC) class II molecules, while CD8+ T-cells recognize peptides of around 9 amino acid residues presented on the surface of MHC class I molecules , 3. FurtThe Immune Epitope Database and Analysis (IEDB) resource is a comprehensive database of experimental epitopes derived from individual low-throughput and high-throughput studies . There aGiven the complexity of experimental assays to measure epitope binding, several tools that predict epitope binding to different MHC alleles based on epitope amino acid sequences have been developed. Predictors such as SYFPEITHI  and BIMAFig 1A–1C) allow an adequate filtering and selection process. In particular, highly conserved epitopes may be good vaccine candidates as they would generate a cross-protective response, not only against the original pathogen but against other strains/types. For example, conserved epitopes against different influenza A and B subtypes have been targeted to elicit protective responses in mice [These predictors often return a large number of predicted T-cell epitopes which need to be further filtered before experimental testing. Epitope features such as the predicted binding strength, the promiscuity , the conservation across homologs, and the location within the amino acid sequence of the antigens . Currently, Epitope-Evaluator recognizes prediction files from NetMHC4.0 [Epitope-Evaluator requires as input: 1) a multi-FASTA file containing the IDs and the sequences of the antigenic proteins, and 2) the respective prediction file previously obtained from a T-cell epitope predictor  The parameters section, 2) the title section, 3) the help section, and 4) the output section . The parameter section, located on the left side of the web application, allows users to set different options and parameters for the corresponding tool. The help section describes the functionality of each tool, details each parameter, and explains the plots and tables returned in the output section. The output section shows the plots and tables from the selected analyses which are downloadable. All the tools contain interactive plots where users can zoom in/out, select regions, and obtain more information by hovering over the plots. The ‘About’ section shows a brief summary of Epitope-Evaluator and specifies the necessary files to run the shiny app. The ‘Run Example’ section contains an example data so users can try the different tools. The ‘Documentation’ section includes the link to the GitHub to download the code and information of the different T-cell epitopes predictors currently supported. In the ‘Tutorial’ section, we have included videos showing the different steps to use the shiny app and the interactivity of each tool.The web server is composed of 6 different sections: ’Home’, ‘About’, ‘Run Example’, ‘Documentation’ and ‘Tutorial’. The ‘Home’ section comprises the Input tab and the 6 different tools available Epitope-Evaluator facilitates the interpretation, visualization, and selection of predicted epitopes. This Shiny app can be used for analyzing MHC Class I and II epitopes and is compatible with any epitope predictor used. More information about the functionalities available in each section, main parameters, and main interface are available in the ‘Run Example’ section where it is also possible to download the sample dataset to use the shiny app. Epitope-Evaluator comprises the following six tools:Fig 2A) or a cumulative histogram . Hovering over any of the histogram bars provides the number of predicted epitopes with a percentile rank lower than a selected cutoff. In addition, the tool shows a heatmap indicating the number of epitopes predicted to bind to each allele with a percentage rank lower than a defined cutoff .This tool helps to identify which MHC Class I or Class II alleles recognize the least (and the greatest) number of epitopes and, therefore, which genotypes could be presenting a weaker T-cell response. For example, patients with MHC alleles recognizing fewer epitopes could be correlated with more severe symptoms during a viral infection. Conversely, patients with MHC alleles recognizing more neo-epitopes could be correlated with a better response during cancer progression or immunotherapies. The Epitope Distribution depicts a histogram representing the number of epitopes within a percentile rank or binding score range allowing an easy identification of the number of strong binder epitopes (lower rank percentile) and weak binder epitopes (higher rank percentile). This histogram can be shown per MHC allele or for the union or intersection of different MHC alleles, which can represent the number of epitopes that can be recognized by a heterozygote individual or the number of epitopes that are recognized by the alleles present in a population, respectively. Users can select between plotting a histogram . In addition to the downloadable plots, the tool provides a table containing the epitope sequences and the number of epitopes within each combination of MHC alleles .Different populations are represented by distinct combinations of MHC alleles. This tool enables users to identify the set of epitopes that could be used in epitope vaccines that are potentially recognized by most/all MHC alleles in the population, as well as to identify epitopes restricted to a particular set of MHC alleles. Users need to select the MCH alleles of interest and a %rank cutoff to identify epitopes. This tool shows the number of epitopes predicted to bind to different MHC allele combinations represented as a Venn Diagram or Up-Set plot if 6 or fewer MHC alleles are selected, or an Up-Set plot if more than 6 MHC alleles are selected . The tool also shows the absolute number of epitopes within each protein predicted to bind to each MHC allele. This visualization can be displayed as a bar plot for a small number of proteins,  and by arranging the set of proteins.This tool can be used to determine the set of proteins containing a high number of predicted epitopes as a first step to finding potentially highly immunogenic proteins, which should then be confirmed experimentally. The tool displays a scatter plot of protein length versus the number of epitopes predicted to bind an MHC allele or combination of alleles .This tool facilitates the visual identification of protein regions enriched or depleted with epitopes. The tool also helps to visualize how different coding mutations impact the increase or decrease of neo-epitopes within pathogenic proteins or oncogenic proteins. The tool can also be used to inform strategies to deimmunize peptide-based drugs by identifying potentially immunogenic epitopes which could then be mutated or deleted. Epitope Viewer graphically represents the position of each predicted epitope within each protein where more promiscuous epitopes are filled with a more intense color. Users must select a cutoff to identify epitopes and the MHC alleles of interest. Choosing the ‘Intersection’ option will show only epitopes predicted to bind to all of the selected MHC alleles. Selecting the ‘Union’ option will display all the epitopes which are colored ranging from yellow to red indicating the number of MHC alleles predicted to bind .This tool facilitates the identification of promiscuous epitopes, which are epitopes predicted to bind to most MHC alleles, and their predicted percentage rank affinity regardless to which protein they belong. This tool allows to identify a list of epitopes that can cover all the MHC alleles of interest. Moreover, with proper selection of the parameters, users are able to perform analyses using only strong binding epitopes or all epitopes. Epitope Promiscuity shows in a heatmap the predicted epitopes that bind to more than a certain number of MHC alleles, set by the user. Users must also indicate the cutoff for both weak and strong binding epitopes. By default, these cutoffs are 0.5 and 2 for MHC Class I epitopes, and 2 and 10 for MHC Class II. If users prefer to analyze only strong binding epitopes, both cutoffs should be set with the same value . The output of this tool is a heatmap where strong binder and weak binder epitopes are indicated as red and orange, respectively. Moreover, the tool returns a table with the sequence of the promiscuous epitopes, their start position within the protein, and the name of the corresponding protein .This tool allows users to identify epitopes that are present in multiple proteins, which can be useful to identify conserved epitopes across different pathogen strains. For example, this tool can be used to identify epitopes shared by all Spike variants from SARS-CoV-2. In addition, this tool allows for identifying epitopes gained or lost by diverse mutations. For this tool, users need to select the proteins, the MHC alleles of interest, and the cutoff percentile rank. The number of shared epitopes is represented as Venn Diagrams/Up-Set plot (≤ 6 proteins) or only Up-Set plot (> 6 proteins) (S1 File).To illustrate the use of Epitope-Evaluator, we analyzed the T-cell epitopes predicted from the SARS-CoV-2 proteome, identified the most antigenic SARS-CoV-2 proteins and regions, and evaluated the density of epitopes across the Spike protein from different SARS-CoV-2 variants. The MHC Class I epitopes were predicted using NetMHCPan  and MHCFEpitope Distribution” tool, we found that each MHC allele recognized a different number of epitopes . Although most MHC Class I alleles recognized around 200 strong binder and 400 weak binder epitopes, the HLA-B*27:05, HLA-B*40:01, and HLA-B*07:02 showed the lowest number of predicted epitopes (~100 strong binder and ~200 weak binder epitopes). Moreover, this observation was not dependent on the percentile rank selected as the same low binder MHC alleles were identified across different percentile rank cutoffs . This suggests that patients with these alleles may have a weaker cytotoxic response against viral infection. The HLA-B*40 allele has been correlated with moderate/severe disease course [The prediction of MHC Class I epitopes from the SARS-CoV-2 proteome resulted in 1,150 strong binder and 1,645 weak binder epitopes, predicted to bind to at least one MHC allele. However, using the “Fig 4B). This suggests that variability in MHC Class II alleles is less likely to be correlated with a worse or better viral response against SARS-CoV-2.We also predicted epitopes binding to MHC Class II, which resulted in 2,245 weak binder and 1,091 strong binder epitopes. Contrary to what we observed for MHC Class I alleles, a similar number of epitopes was predicted to bind each MHC Class II allele regardless of the cutoff selected .As a first step to design recombinant vaccines, we identified the SARS-CoV-2 proteins enriched in MHC Class I and Class II epitopes, using the ‘Epitope Density’ tool. As expected, we found that R1AB and R1A, which are the largest SARS-CoV-2 proteins, contained the highest number of MHC Class I epitopes in total . From the remaining proteins, we show that Spike (S), Nucleocapsid (N), ORF3A and Membrane (M) proteins contain the highest number of MHC-Class I. Moreover, these proteins contain at least one MHC Class I epitope predicted to bind to each MHC allele, which suggests a broader protection . Altogether, these results suggest that proteins N, M and ORF3 could also be considered complementary vaccine antigens, as previously suggested [Similarly, R1AB and R1A contained the highest number of MHC Class II epitopes in total . From the remaining, we found that S, N, M and ORF3A also contained the highest number of MHC-Class II epitopes. These proteins also contained at least one epitope predicted to bind to each MHC-Class II allele (uggested –23.S1 File) and determined whether MHC Class II alleles were predicted to recognize fewer epitopes due to the mutations in each variant by using the “Epitope Density” tool. We found that Wuhan Spike contains a similar number of epitopes as other Spike variants for each MHC Class II allele , suggesting that mutations in current variants do not have a marked impact on the recognition of epitopes by MHC class II alleles. We then used the ‘Epitope Promiscuity’ tool to identify highly promiscuous epitopes and determine whether these epitopes were affected by the mutations in the Spike variants. We identified five epitopes binding to at least 7 MHC Class II alleles and all five were present in the six Spike variants, suggesting that these epitopes may be well suited for epitope vaccines as they are recognized by most MHC Class II alleles and are present in all current variants .We predicted MHC Class II epitopes from the Alpha, Beta, Gamma, Delta, Omicron and Wuhan Spike variants . This is consistent with the higher number of mutations in Omicron Spike compared to Delta Spike [Fig 4H). Altogether, our analyses suggest that, although Spike variants can escape from certain antibodies elicited by vaccines against the Wuhan and Omicron Spike, the T-helper response may remain efficient, as demonstrated in other works [Next, we evaluated whether MHC Class II epitopes identified from Wuhan Spike are conserved in the variants of concern (Delta and Omicron variants). These epitopes could suggest cross-protection across variants when immunized against Wuhan Spike as it is the antigen used in most current SARS-CoV-2 vaccines. Using the ‘Epitope Conservation’ tool we determined the number of epitopes shared, gained, and lost, by mutations in Delta and Omicron. We identified 212 epitopes shared across the three variants, 21 and 18 epitopes were lost and gained in the Delta variant, and 89 and 63 epitopes were lost and gained in the Omicron variant, respectively , expression level, and potential toxicity. These parameters are case-specific and are therefore not considered by Epitope-Evaluator.As an example, we used Epitope-Evaluator to analyze the MHC Class I and Class II epitopes from the SARS-CoV-2 proteome. Our analysis confirmed previously reported results such as the potential of N and M proteins as complementary candidate vaccines , 33. OurFuture directions include adding new T-cell predictors, developing tools for analyzing B-cell epitopes and new ways to integrate MHC Class I T-cell epitopes, MHC Class II T-cell epitopes, and B-cell epitopes. Moreover, gene expression data for the antigens can be included to prioritize epitopes of highly expressed genes. Altogether, this tool will assist immunologists and experimental scientists to interpret and analyze T-cell epitopes.S1 File(DOCX)Click here for additional data file.