bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improved antibody structure prediction by deep learning of side chain conformations
Authors: Akpinaroglu Deniz , Ruffolo Jeffrey A. , Mahajan Sai Pooja , Gray Jeffrey J. 
Published: September 2021

AbstractAntibody engineering is becoming increasingly popular in medicine for the development of diagnostics and immunotherapies. Antibody function relies largely on the recognition and binding of antigenic epitopes via the loops in the complementarity determining regions. Hence, accurate high-resolution modeling of these loops is essential for effective antibody engineering and design. Deep learning methods have previously been shown to effectively predict antibody backbone structures described as a set of inter-residue distances and orientations. However, antigen binding is also dependent on the specific conformations of surface side chains. To address this shortcoming, we created DeepSCAb: a deep learning method that predicts inter-residue geometries as well as side chain dihedrals of the antibody variable fragment. The network requires only sequence as input, rendering it particularly useful for antibodies without any known backbone conformations. Rotamer predictions use an interpretable self-attention layer, which learns to identify structurally conserved anchor positions across several species. We evaluate the performance of our model for discriminating near-native structures from sets of decoys and find that DeepSCAb outperforms similar methods lacking side chain context. When compared to alternative rotamer repacking methods, which require an input backbone structure, DeepSCAb predicts side chain conformations competitively. Our findings suggest that DeepSCAb improves antibody structure prediction with accurate side chain modeling and is adaptable to applications in docking of antibody-antigen complexes and design of new therapeutic antibody sequences.
Cerebrospinal fluid amyloid beta and glial fibrillary acidic protein concentrations in Huntington’s disease
Authors: Korpela Sara , Sundblom Jimmy , Zetterberg Henrik , Constantinescu Radu , Svenningsson Per , Paucar Martin , Niemelä Valter 
Published: September 2021

AbstractIntroductionHuntington’s disease (HD) is a genetic incurable lethal disease. Biomarkers are needed for objective assessment of disease progression. Evidence supports both complex protein aggregation and astrocyte activation in HD. This study assesses the 42 amino acid long amyloid beta (Aβ42) and glial fibrillary acidic protein (GFAP) as potential biomarkers in the cerebrospinal fluid (CSF) of HD mutation carriers.MethodsCSF was obtained from manifest HD patients (ManHD), premanifest HD-gene-expansion carriers (PreHD) and gene-negative controls (controls). Disease Burden Score (DBS) and Total Functional Capacity (TFC) were calculated. Protein concentrations were measured by enzyme-linked immunosorbent assays (ELISA) and intergroup differences were analysed using Mann-Whitney U test. Spearman correlations were calculated to assess disease stage association. Age-adjustment was included in the statistical tests.ResultsThe study enrolled 27 ManHD and 13 PreHD subjects. The number of controls differed in the analysis of Aβ42 and GFAP (n = 19, and 8 respectively). Aβ42 levels were higher in ManHD (mean 741 ng/l, SD 361) compared with PreHD (mean 468 ng/l, SD 184) (p = 0.025). Likewise GFAP concentration was higher in ManHD (mean 435 ng/l, SD 255) compared with both PreHD (mean 266 ng/l, SD 92.4)(p = 0.040) and controls (mean 208 ng/l, SD 83.7)(p = 0.011). GFAP correlated with DBS (r = 0.361, p = 0.028), TFC (r = − 0.463, p = 0.005), and 5-year risk of onset in PreHD (r = 0.694, p = 0.008). In contrast, there was no correlation between Aβ42 concentration and DBS, TFC or 5-year risk of onset.ConclusionCSF Aβ42 levels did not correlate with disease stage suggesting no Aβaggregation in HD. GFAP is a potential biomarker in HD with association to disease stage. Validation in larger HD cohorts and potential correlations with clinical phenotype would be of interest.
Magnetic Particle Imaging is a sensitivein vivoimaging modality for the quantification of dendritic cell migration
Authors: Gevaert Julia J. , Fink Corby , Dikeakos Jimmy , Dekaban Gregory A. , Foster Paula J. 
Published: September 2021

AbstractImmunotherapies, such as dendritic cell- (DC-)based therapies, are useful for treating cancer as an alternative to or in combination with traditional therapies. Cells must migrate to lymphoid organs to be effective and the magnitude of the ensuing T cell response is proportional to the number of lymph node-migrated DC. With less than 10% of cells expected to reach their destination, there is a need for an imaging modality capable of sensitively and quantitatively detecting cells. MRI has been used to track DC using iron and 19F methods, with limitations. Quantification of iron-induced signal loss is indirect and challenging; 19F signal is directly quantifiable but lacks sensitivity. Magnetic Particle Imaging (MPI) directly detects superparamagnetic iron oxide nanoparticles (SPIO) and enables quantitation of low numbers of SPIO-labeled cells. Here we describe the first study using MPI to track and quantify the migration of DC, injected into the footpads of C57BL/6 mice, to the popliteal lymph nodes (pLNs). As DC migrate from the site of injection to the lymph nodes, we measured a decrease in signal in the footpads and an increase in signal at the pLNs. The presence of SPIO-labeled DC in nodes was validated byex vivoMPI and histology. By measuring the iron mass per cell in samples of labeled cells, we were able to provide an estimate of cell number for each source of signal and we report a sensitivity of approximately 4000 cellsin vivoand 2000 cellsex vivo. For some mice, MPI was compared to cellular MRI. We also bring attention to the issue of resolving unequal signals within close proximity, a challenge for many pre-clinical studies using a highly concentrated tracer bolus that over shadows nearby lower signals. This study demonstrates the clear advantage of MPI to detect and quantify cellsin vivo, bridging the gap left by cellular MRI, and all otherin vivoimaging modalities, and opening the door for quantitative imaging of cellular immunotherapies.
The connection between Rap1 and Talin1 in CD4+ T Lymphocytes
Authors: Lagarrigue Frederic , Tan Boyang , Du Qinyi , Fan Zhichao , Lopez-Ramirez Miguel A. , Gingras Alexandre R , Qi Weiwei , Sun Hao 
Published: September 2021

AbstractAgonist induced increase in integrin affinity for ligands (activation) plays a pivotal role in T cell trafficking and functions. Activation requires Rap1 GTPase-mediated recruitment of talin1 to the integrins in the plasma membrane. Rap1-interacting adaptor molecule (RIAM) is a Rap1 effector that serves this function in T cells. In addition, Rap1 directly binds to talin1 to enable integrin activation in platelets. Here, we assessed the relative contributions of the Rap1-talin1 interaction and RIAM and provide a complete accounting of the connections between Rap1 and talin1 that support integrin activation in conventional CD4+ (Tconv) and CD25HiFoxp3+CD4+ regulatory T (Treg) cells. Disruption of both Rap1 binding sites in talin1 (talin1 (R35E,R118E)) causes a partial defect in αLβ2, α4β1 and α4β7 integrin activation in both Tconv and Treg cells with resulting defects in T cell homing and functions. Over-expression of RIAM bypasses the integrin activation defect in Tconv cells expressing talin1 (R35E,R118E), indicating that RIAM can substitute for Rap1 binding to talin in integrin activation. Conversely, deletion of RIAM in talin1 (R35E,R118E) Tconv cells abrogates activation of αLβ2, α4β1 and α4β7. RIAM and lamellipodin (LPD) are mammalian members of the MRL protein family; LPD plays a more important role than RIAM in Treg cell integrin activation. Nevertheless, loss of RIAM profoundly exacerbates the defects in Treg cell function caused by the talin1 (R35E,R118E) mutation. Most importantly, deleting both MRL proteins combined with talin1 (R35E,R118E) phenocopies the complete lack of integrin activation observed in Rap1a/b null Treg cells. In sum, these data reveal the functionally significant connections between Rap1 and talin1 that enable αLβ2, α4β1 and α4β7 integrin activation in T cells.
Deciphering the role of the Pancreatic Secretome in Covid-19 associated Multi-Organ Dysfunctions
Authors: Pathak Ekta , Mishra Rajeev 
Published: September 2021

SummaryEmerging evidence indicates an intricate relationship between the SARS-CoV-2 infection and Multi-Organ Dysfunctions (MODs). Here, we have investigated the role of the Secretome of the SARS-CoV-2 infected pancreas and mechanistically linked it with the multi-organ dysfunction using the scRNA-seq analysis. We found that acinar-specific PRSS2, REG3A, REG1A, SPINK1, and ductal-specific SPP1, MMP7 genes are upregulated in alpha, beta, delta, and mesenchyme cells. Using extensive documented experimental evidence, we validated the association of upregulated pancreatic Secretome with coagulation cascade, complement activation, renin angiotensinogen system dysregulation, endothelial cell injury and thrombosis, immune system dysregulation, and fibrosis. Our finding suggests the influence of upregulated Secretome on multi-organ systems such as Nervous, Cardiovascular, Immune, Digestive, and Urogenital systems. In addition, we report that the secretory proteins IL1B, AGT, ALB, SPP1, CRP, SERPINA1, C3, TFRC, TNFSF10, and MIF are associated with diverse diseases. Thus, suggest the role of the pancreatic Secretome in SARS-CoV-2 associated MODs.
Modelling 3D tumour microenvironment in vivo: a tool to predict cancer fate
Authors: Marines J. , Lorenzini F. , Kissa K. , Fontenille L. 
Published: September 2021

AbstractRecently, many studies demonstrated the fundamental role of tumour microenvironment (TME) in cancer progression. Here, we describe a state-of-the-art method to visualize in 3D the behaviour of tumours in zebrafish embryos. We highlight two major actors of TME, macrophages and vessels. This valuable tool is transposable to Patients Derived Xenograft imaging in order to predict the fate of malignant tumours according to the dynamics of their TME.
Assessing the importance of transformational leadership competencies and supply chain learning to green innovation: construction practitioners’ perspectives
Authors: Pham Hai , Pham Tho , Dang Chau Ngoc 
Published: September 2021

Purpose
This study aims to assess the importance of transformational leadership competencies, as well as supply chain learning, to green innovation in construction at the supply chain level.

Design/methodology/approach
A questionnaire survey is conducted to collect data from construction firms in Vietnam. Many statistical analysis methods – including the Shapiro-Wilk test, one-sample Wilcoxon signed-rank test and Kruskal-Wallis test – are performed to achieve the research objectives.

Findings
The results indicate that the importance of most transformational leadership competencies is similarly perceived among different role groups (i.e. directors/deputy directors, project managers, consultants, quantity surveyors and designers).

Research limitations/implications
This study enriches the understanding of leadership research in construction at the supply chain level and also develops a theoretical framework for theory testing research, where the relationships of transformational leadership competencies and supply chain learning with green innovation are highlighted.

Originality/value
Research on leadership in the green supply chain context is still limited, especially in the construction industry. Thus, this study is conducted to fill this gap of research.
MCS package and entrepreneurial competency influence on business performance: the moderating role of business strategy
Authors: Rehman Shafique Ur , Elrehail Hamzah , Nair Kiran , Bhatti Anam , Taamneh Abdallah Mohammad 
Published: September 2021

PurposeThis paper draws on resource-based theory (RBV) to examine the impact of the management control system (MCS) package on business performance through the mediating role of entrepreneurial competencies and the interaction role of business strategy in small and medium-sized enterprises (SMEs).Design/methodology/approachA total of 372 questionnaires were used in this research for analysis purposes using partial least square–structural equation modelling. Cluster sampling was used and nine states out of 16 states were selected randomly, including Kelantan, Johor, Sarawak, Selangor, Kedah, Kuala Lumpur, Penang, Perak and Sabah, because the nine states cover 84.4% of the total SMEs.FindingsThe results revealed that only cultural and administrative control has no relationship with business performance. Moreover, in the MCS package, all elements have a significant and positive influence on entrepreneurial competencies. Furthermore, business strategy (cost leadership and differentiation strategy) significantly moderates, while entrepreneurial competencies mediate between, cultural, planning, cybernetic, rewards and compensation, administrative control and business performance.Originality/valueSMEs in Malaysia are contributing 36.6% to gross domestic product. Further, as this sector is important, less attention has been paid to this area of MCS package with business strategies to determine organisational performance. This study fills these gaps, and the recommendations and findings for further research are discussed in detail accordingly. Moreover, the findings of the current research provide guidelines for the management of SMEs.
Effectiveness of travel time during evacuation in high-rise residential buildings: a case study in Selangor, Malaysia
Authors: Gian Caleb Michealangelo , Mohd Tohir Mohd Zahirasri , Md Said Mohamad Syazarudin , Tharima Ahmad Faiz , Mohd Nizam Ong Nur Aliah Fatin , Ramali Mohd Rashid 
Published: September 2021

Purpose
In recent years, the number of high-rise buildings in Malaysia has been increasing. Therefore, it is essential to take evacuation into consideration especially for emergency conditions such as fire, explosion and natural disasters. This research aims to evaluate the effectiveness of the escape time in typical Malaysian high-rise residential buildings.

Design/methodology/approach
This work comprises simulation on three buildings around the Selangor area in Malaysia. Quantitative methodology is adopted using Pathfinder software to simulate the evacuation process and time of the three typical Malaysian high-rise residential buildings. Four parameters were studied namely, the occupant load density, walking speed of first and last occupants, average of evacuation time per floor for the three buildings and effect of placement of emergency staircase on travel time.

Findings
Findings show that 12 m2 which is double the allowable occupants' density in Malaysia increases evacuation time by 67.9% while the placement of the emergency staircase on the left and middle section of a building significantly affects the evacuation time by 21.2%. In conclusion, from the simulation studies, it is recognized that a higher occupant's density affects the evacuation time.

Originality/value
This work could provide information on escape time for future construction of high-rise buildings in Malaysia. Hence, the specification and design of buildings could be reviewed based on the results obtained from this simulation. This information could be beneficial to the building regulators and developers thus enhancing the knowledge of building constructor and possible issues in the design of staircases, corridors and height of buildings.
A structural relationship model of gender-role orientation and entrepreneurial intention: examining the mediating effect of motivational antecedents in Northeast India
Authors: Passah Kiefe Heibormi , Panda Nagari Mohan 
Published: September 2021

PurposeThe paper presents a structural model to explain the relationship between various gender-role orientations (GROs) and motivational antecedents leading to entrepreneurial intention (EI). It examines the influence of GRO in the formation of EI among educated youths of Northeast India.Design/methodology/approachUsing a structural equation modelling approach, the hypothesized model is tested on a sample of 642 post-graduate students from four different universities in Northeast India, a developing region with unique socio-cultural diversity. The mediating role of EI antecedents on the relationship between GRO and EI was examined after establishing the reliability and validity of the measurement model.FindingsResults from the analysis support the hypothesized structural relationship confirming the influence of GRO on EI. The study also finds that androgynous individuals have a higher EI than their masculine or feminine counterparts.Research limitations/implicationsThe study contributes to the understanding of EI determinants from a GRO perspective, especially in the industrially backward region of an emerging economy. It adds to the existing literature by empirically proving the role of gender orientation. The results have several policy implications for educational institutions and policymakers in emerging economies.Originality/valueThe paper re-examines the predictive value of the theory of planned behaviour (TPB) model from a GRO perspective and compares indirect effects of gender identity through motivational antecedents on EI. Whilst TPB predicted EI in Western and developed countries, using a more diverse sample provides strong empirical evidence in the context of a developing region.
A robust multiobjective solution approach for mean-variance optimisation of correlated multiple quality characteristics
Authors: Sharma Abhinav Kumar , Mukherjee Indrajit , Bera Sasadhar , Sengupta Raghu Nandan 
Published: September 2021

PurposeThe primary objective of this study is to propose a robust multiobjective solution search approach for a mean-variance multiple correlated quality characteristics optimisation problem, so-called “multiple response optimisation (MRO) problem”. The solution approach needs to consider response surface (RS) model parameter uncertainties, response uncertainties, process setting sensitivity and response correlation strength to derive the robust solutions iteratively.Design/methodology/approachThis study adopts a new multiobjective solution search approach to determine robust solutions for a typical mean-variance MRO formulation. A fine-tuned, non-dominated sorting genetic algorithm-II (NSGA-II) is used to derive efficient multiobjective solutions for varied mean-variance MRO problems. The iterative search considers RS model uncertainties, process setting uncertainties and response correlation structure to derive efficient fronts. The final solutions are ranked based on two different multi-criteria decision-making (MCDM) techniques.FindingsFive different mean-variance MRO cases are selected from the literature to verify the efficacy of the proposed solution approach. Results derived from the proposed solution approach are compared and contrasted with the best solution(s) derived from other approaches suggested in the literature. Comparative results indicate significant superiorities of the top-ranked predicted robust solutions in nondominated frequency, closeness-to-target and response variabilities.Research limitations/implicationsThe solution approach depends on RS modelling and considers continuous search space.Practical implicationsIn this study, promising robust solutions are expected to be more suitable for implementation than point estimate-based MOO solutions for a real-life MRO problem.Originality/valueNo evidence of earlier research demonstrates the superiority of a MOO-based iterative solution search approach for mean-variance MRO problems by simultaneously considering model uncertainties, response correlation and process setting sensitivity.
Development of a novel robotic hand with soft materials and rigid structures
Authors: Li Yongyao , Cong Ming , Liu Dong , Du Yu , Wu Minjie , de Silva Clarence W. 
Published: September 2021

Purpose
Rigid robotic hands are generally fast, precise and capable of exerting large forces, whereas soft robotic hands are compliant, safe and adaptive to complex environments. It is valuable and challenging to develop soft-rigid robotic hands that have both types of capabilities. The paper aims to address the challenge through developing a paradigm to achieve the behaviors of soft and rigid robotic hands adaptively.

Design/methodology/approach
The design principle of a two-joint finger is proposed. A kinematic model and a stiffness enhancement method are proposed and discussed. The manufacturing process for the soft-rigid finger is presented. Experiments are carried out to validate the accuracy of the kinematic model and evaluate the performance of the flexible body of the finger. Finally, a robotic hand composed of two soft-rigid fingers is fabricated to demonstrate its grasping capacities.

Findings
The kinematic model can capture the desired distal deflection and comprehensive shape accurately. The stiffness enhancement method guarantees stable grasp of the robotic hand, without sacrificing its flexibility and adaptability. The robotic hand is lightweight and practical. It can exhibit different grasping capacities.

Practical implications
It can be applied in the field of industrial grasping, where the objects are varied in materials and geometry. The hand’s inherent characteristic removes the need to detect and react to slight variations in surface geometry and makes the control strategies simple.

Originality/value
This work proposes a novel robotic hand. It possesses three distinct characteristics, i.e. high compliance, exhibiting discrete or continuous kinematics adaptively, lightweight and practical structures.
Should we engage variety seeking customers?
Authors: Gupta Ashish , Pandey Shivendra 
Published: September 2021

Purpose
The study aims to examine the moderating role of variety-seeking behaviour between customer engagement and its antecedents (customer satisfaction and customer value). Further, this study also tests the existence of the value-satisfaction-engagement behaviour chain.

Design/methodology/approach
The perception of 262 respondents was used to examine the hypothesis using the structural equation modelling approach.

Findings
The moderation effect of variety-seeking behaviour between customer satisfaction and customer engagement was found to be significant. Also, customer satisfaction fully mediated the relationship between perceived value and customer engagement, hence, empirically validating the value-satisfaction-engagement model in the retailing context.

Research limitations/implications
The findings draw managers' attention towards the segment of consumers who are more likely to be engaged, thus helping managers develop a more efficient and focussed strategy to achieve customer engagement. The result also suggests that variety-seeking buyers may not get engaged even after satisfaction.

Originality/value
This paper is among the first to empirically test the moderating role of variety-seeking behaviour to achieve customer engagement.