Library Design Research Articles

Seeing a Sea of Ships - Exploring the Ship Design Space in the Digital Domain

We tackle in this work aspects of the ship design space in the digital domain, with an overview of the current status and opportunities to shift from fixed arrangements towards open technologies, proposing a mix of open and proprietary databases. The discussion is focused on the visual domain and digital thread in ship design. Literature examples from the Brazilian case and the visualization of the ocean space are presented (Numerical Offshore Tank - TPN), followed by the Japanese services to design and optimize hull for specific missions (NMRI), and lastly the current open ship design library developed in Norway (Vessel.js, NTNU). We present the argument that seeing a sea of ships, that is, visualizing the behavior of many options is already a reality, accessible from a portable device, without the need a large cluster as in the past, exemplified by web-based cases. Our conclusion is that computer graphics approaches to Ship Design should be considered open and exchangeable. Naval architects should focus on what they do best: creating, analyzing, refining, storing and populating the database of the know-how from the institution (e.g. university, research institute or company).

Regulation of cerebral blood flow boosts precise brain targeting of vinpocetine-derived ionizable-lipidoid nanoparticles

Despite advances in active drug targeting for blood-brain barrier penetration, two key challenges persist: first, attachment of a targeting ligand to the drug or drug carrier does not enhance its brain biodistribution; and second, many brain diseases are intricately linked to microcirculation disorders that significantly impede drug accumulation within brain lesions even after they cross the barrier. Inspired by the neuroprotective properties of vinpocetine, which regulates cerebral blood flow, we propose a molecular library design centered on this class of cyclic tertiary amine compounds and develop a self-enhanced brain-targeted nucleic acid delivery system. Our findings reveal that: (i) vinpocetine-derived ionizable-lipidoid nanoparticles efficiently breach the blood-brain barrier; (ii) they have high gene-loading capacity, facilitating endosomal escape and intracellular transport; (iii) their administration is safe with minimal immunogenicity even with prolonged use; and (iv) they have potent pharmacologic brain-protective activity and may synergize with treatments for brain disorders as demonstrated in male APP/PS1 mice.

Assessing Users’ Demand for Library Space: Insights from an Architecture School

The purpose of this paper is to conduct a post-occupancy evaluation to assess users’ feedback on the use of the architecture school library at Thammasat University, Thailand. The proposed study also has a specific objective: to explore users’ demand for library space in terms of academic library attributes. A case study of the library in the Faculty of Architecture and Planning was conducted at Thammasat University. Multiple data collection methods were used, including document analysis, a questionnaire survey, a workshop, and focus group interviews, to gather information on users’ demand for the library space. The findings confirm the relevance of the variables in the conceptual model from previous studies, which encompass three key attributes regarding users’ demand for library space: physical, social, and digital spaces. Functional obsolescence and changing learning approaches are revealed as dominant influential factors affecting users’ demand for library space. The connection between post-occupancy evaluation (POE) and pre-design evaluation (PDE) in the redevelopment of a real estate project is considered as a shift from performance measurement to performance management, assisting in establishing agreed-upon performance goals for the operation. This study’s findings, derived from a single case study, do affect affect generalisability. However, the study provides insights into academic library design and renovation by emphasising the alignment of library spaces with user needs for improved service effectiveness and user satisfaction. The research introduces an integration of POE and PDE, proposing a methodological framework for future library space redevelopment that could contribute to the broader discussion on library design and user experience.

DigCode—A generic mid-air gesture coding method on human-computer interaction

With high flexibility and rich semantic expressiveness, mid-air gesture interaction is an important part of natural human-computer interaction (HCI) and has broad application prospects. However, there is no unified representation frame for designing, recording, investigating and comparing HCI mid-air gestures. Therefore, this paper proposes an interpretable coding method, DigCode, for HCI mid-air gestures. DigCode converts the unstructured continuous actions into structured discrete string encoding. From the perspective of human cognition and expression, the research employed psychophysical methods to divide gesture actions into discrete intervals, defined the coding rules of representation in letters and numbers, and developed automated programs to enable encoding and decoding by using gesture sensors. The coding method can cover the existing representations of HCI mid-air gestures by considering human understanding and computer recognition and can be applied to HCI mid-air gesture design and gesture library construction.

SynDesign: web-based prime editing guide RNA design and evaluation tool for saturation genome editing.

Saturation genome editing (SGE) enables in-depth functional evaluation of disease-associated genes and variants by generating all possible single nucleotide variants (SNVs) within a given coding region. Although prime editing can be employed for inducing these SNVs, designing efficient prime editing guide RNAs (pegRNAs) can be challenging and time-consuming. Here, we present SynDesign, an easy-to-use webtool for the design, evaluation, and construction precision pegRNA libraries for SGE with synonymous mutation markers. SynDesign offers a simple yet powerful interface that automates the generation of all feasible pegRNA designs for a target gene or variant of interest. The pegRNAs are selected using the state-of-the-art models to predict prime editing efficiencies for various prime editors and cell types. Top-scoring pegRNA designs are further enhanced using synonymous mutation markers which improve pegRNA efficiency by diffusing the cellular mismatch repair mechanism and serve as sequence markers for improved identification of intended edits following deep sequencing. SynDesign is expected to facilitate future research using SGE to investigate genes or variants of interest associated with human diseases. SynDesign is freely available at https://deepcrispr.info/SynDesign without a login process.

Changes in Active Site Loop Conformation Relate to the Transition toward a Novel Enzymatic Activity.

Enzymatic promiscuity, the ability of enzymes to catalyze multiple, distinct chemical reactions, has been well documented and is hypothesized to be a major driver of the emergence of new enzymatic functions. Yet, the molecular mechanisms involved in the transition from one activity to another remain debated and elusive. Here, we evaluated the redesign of the active site binding cleft of lactonase SsoPox using structure-based design and combinatorial libraries. We created variants with largely improved catalytic abilities against phosphotriesters, the best ones being >1000-fold better compared to the wild-type enzyme. The observed shifts in activity specificity are large, and some variants completely lost their initial activity. The selected combinations of mutations have considerably reshaped the active site cavity via side chain changes but mostly through large rearrangements of the active site loops and changes to their conformations, as revealed by a suite of crystal structures. This suggests that a specific active site loop configuration is critical to the lactonase activity. Interestingly, analysis of high-resolution structures hints at the potential role of conformational sampling and its directionality in defining the enzyme activity profile.

An Experimental Research of the Algorithm for Extracting of a Boolean Function Subsystems for Joint Multilevel Optimization

The results of an experimental comparison of programs for technologically independent minimization of complexity of multilevel representations of systems of fully defined functions based on the Shannon expansion are described. The main attention is paid to the effectiveness of using, when synthesizing logical circuits, a program that implements an algorithm for solving the problem of extracting from a system of functions such subsystems for which it is advisable to carry out joint minimization of multi-level representations of subsystems in the form of Binary Decision Diagrams, called BDD-representations, and in the form of Boolean net. The complexity of the representation is estimated by the total number of literals of Boolean variables in a set of interrelated logical equations that define a system of Boolean functions. After extracting the subsystems and their joint minimization, the synthesis of logic circuits is carried out in the design library of custom digital CMOS VLSIs, the results are compared in terms of chip area and speed (time delay) on a stream of 39 industrial examples of circuits. It was found that for 20 examples, the subsystem selection algorithm allows one to obtain better solutions than joint or separate minimization of multi-level representations based on Shannon expansion (13 examples). The three best solutions are obtained by applying the well-known Espresso program for minimizing functions in the DNF class, and the three solutions are obtained by the synthesizer using the original (non-optimized) matrix representations of DNF systems of Boolean functions.

Keterikatan Warna dan Emosi dalam Mebeler Bagi Pemustaka Tuli di Perpustakaan UIN Sunan Kalijaga

This study aims to investigate the association to furniture color and emotion for deaf users in libraries, who often experience limited accessibility. However, few studies have focused on the relationship between color-emotion associations to furniture and the experience of deaf users. The purpose of this research is to find out how colours is associated with furniture, which benefit the emotions and comfort to the deaf library user. This study uses qualitative research methods with in-depth interview techniques and participatory observation at the UIN Sunankalijaga Library in Yogyakarta. The findings of this study entailed how the uniqueness of colour was attached and functional with furniture. Major impact on emotions, where its produce a favourable experience for deaf guests. While in the library, the application of certain hues colour and design aspects provide a sense of comfort, relaxation, and concertration. The cool colours, such as green, which paired with neutral colours in furniture products or vice versa are shown to increase mood. Indeed, this study adds to our understanding of the psychological and social elements of deaf users' furnishings. Practical ideas for library managers and designers on how to create an inclusive library environment and fulfil the needs of deaf visitors through furnishing products that was generated.

Design and construction of a phage-displayed Camelid nanobody library using a simple bioinformatics method

BackgroundRational design of synthetic phage-displayed libraries requires the identification of the most appropriate positions for randomization using defined amino acid sets to recapitulate the natural occurrence. The present study uses position-specific scoring matrixes (PSSMs) for identifying and randomizing Camelidae nanobody (VHH) CDR3. The functionality of a synthetic VHH repertoire designed by this method was tested for discovering new VHH binders to recombinant coagulation factor VII (rfVII). MethodsBased on PSSM analysis, the CDR3 of cAbBCII10 VHH framework was identified, and a set of amino acids for the substitution of each PSSM-CDR3 position was defined. Using the Rosetta design SwiftLib tool, the final repertoire was back-translated to a degenerate nucleotide sequence. A synthetic phage-displayed library was constructed based on this repertoire and screened for anti-rfVII binders. ResultsA synthetic phage-displayed VHH library with 1 × 108 variants was constructed. Three VHH binders to rfVII were isolated from this library with estimated dissociation constants (KD) of 1 × 10−8 M, 5.8 × 10−8 M and 2.6 × 10-7 M. ConclusionPSSM analysis is a simple and efficient way to design synthetic phage-displayed libraries.

Structural Survey of Antigen Recognition by Synthetic Human Antibodies.

Synthetic antibody libraries have been used extensively to isolate and optimize antibodies. To generate these libraries, the immunological diversity and the antibody framework(s) that supports it outside of the binding regions are carefully designed/chosen to ensure favorable functional and biophysical properties. In particular, minimalist, single-framework synthetic libraries pioneered by our group have yielded a vast trove of antibodies to a broad array of antigens. Here, we review their systematic and iterative development to provide insights into the design principles that make them a powerful tool for drug discovery. In addition, the ongoing accumulation of crystal structures of antigen-binding fragment (Fab)-antigen complexes generated with synthetic antibodies enables a deepening understanding of the structural determinants of antigen recognition and usage of immunoglobulin sequence diversity, which can assist in developing new strategies for antibody and library optimization. Toward this, we also survey here the structural landscape of a comprehensive and unbiased set of 50 distinct complexes derived from these libraries and compare it to a similar set of natural antibodies with the goal of better understanding how each achieves molecular recognition and whether opportunities exist for iterative improvement of synthetic libraries. From this survey, we conclude that despite the minimalist strategies used for design of these synthetic antibody libraries, the overall structural interaction landscapes are highly similar to natural repertoires. We also found, however, some key differences that can help guide the iterative design of new synthetic libraries via the introduction of positionally tailored diversity.

Abstract LB161: Discovery of an oral, potent, and selective CDK9 molecular glue degrader SLX-3065 active in aggressive variant prostate cancers (AVPC)

Abstract Background: The use of new potent targeted therapies in prostate cancers has led to the resistance and development of highly aggressive variant prostate cancers (AVPC), including neuroendocrine prostate cancers (NEPC). N-MYC and C-MYC oncogenes overexpress in all aggressive prostate cancers (PCa). This overexpression is highly prevalent in these lethal subtypes of cancers, detected in 2% of all Prostate Cancers and over 10-17% of mCRPC patients. Transcriptional targets of CDK9 are MYCs, which act as an oncogenic driver, sufficient to transform human-derived prostate cancer cells to take on AVPC and NEPC phenotypic changes. Additionally, N-MYC and C-MYC play key roles in tumor drug resistance, and their downregulation, through CDK9 inhibition or degradation lowers tumor growth. Our efforts have demonstrated that targeting drivers of NEPC and mCRPC with highly selective CDK9 molecular glue degraders SLX-3064 SLX-3065 was designed from reversible SLX-3039 for therapeutic intervention of mCRPC, AVPC, and NEPCs. Materials and Methods: We employed our MolecuLernTM-trained molecular glue library design strategies and in vitro CDK9 kinase binding assays. Other experiments include cellular efficacies of single-agent Molecular Glue degraders and their effect in combination experiments on 22Rv1, LASCPC-01, C4-2, and C4-2B MYC expressed PCa cells. Kinase selectivity, Nano BRET, ADME-Tox, in vitro safety, secondary pharmacological assays, Cell engraftment mouse tumor mode, and PK studies were performed. Results: We designed and synthesized a series of novel small molecule CDK9 Molecular Glue degraders based on our initial CDK9 inhibitor lead SLX-3030 and SLX-3039. The SLX-3064 and SLX-3065 reversibly bind to CDK9 with an IC50 of 9 and 7 nM in kinase binding, in target engagement assays, elicit pharmacological responses in N-MYC, C-MYC, driven prostate cancer cells in vitro in LASCPC-01 (21, 35 nM), 22Rv1 (108, 236 nM), C4-2B (15, 12 nM), C4-2 (2.7, 1.5 nM) and VCap (86, 73 nM) cell lines. SLX-3064 and SLX-3065 exhibited potent activity degrading total, pCDK9, MYCs, Mcl-1, and its downstream RNA Pol II, Ser 2, 5, 7, and pAR Ser-81 in a dose-dependent manner. Additionally, we performed in vitro ADME-Tox, hERG, P450, safety panel screen, and in vivo PK experiments in rodent and beagle dog species. Conclusion: In summary, both SLX-3064 and SLX-3065 molecular glues display complete degradation of CDK9 and its downstream markers, and these degraders possess ideal developable criteria as oral agents. With these characteristics, SLX-3065 was selected as a candidate that had the appropriate developable properties and our plans for conducting additional IND-enabling studies and future clinical trial plans will also be discussed. Citation Format: Chenyu Lin, Zhaoliang Li, Kyle Medley, David J. Bearss, Hariprasad Vankayalapati. Discovery of an oral, potent, and selective CDK9 molecular glue degrader SLX-3065 active in aggressive variant prostate cancers (AVPC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB161.

Plans to Weed: An Investigation into the State of North American Reference Collections Supporting Art and Design

ABSTRACT This paper aims to shed light on the state of the Reference Collection in post-secondary Art and Design libraries. Recent trends indicate that the availability of electronic research tools is a factor in institutions dismantling their print collections; however, others have argued for retaining them for their convenience, low cost, and even for their value as training tools. This research seeks to determine what types of reference collections art and design libraries are maintaining, how they are using and promoting them, and what considerations go into their removal.

Sequence-based design and construction of synthetic nanobody library.

Nanobody (Nb), the smallest antibody fragments known to bind antigens, is now widely applied to various studies, including protein structure analysis, bioassay, diagnosis, and biomedicine. The traditional approach to generating specific nanobodies involves animal immunization which is time-consuming and expensive. As the understanding of the antibody repertoire accumulation, the synthetic library, which is devoid of animals, has attracted attention widely in recent years. Here, we describe a synthetic phage display library (S-Library), designed based on the systematic analysis of the next-generation sequencing (NGS) of nanobody repertoire. The library consists of a single highly conserved scaffold (IGHV3S65*01-IGHJ4*01) and complementary determining regions of constrained diversity. The S-Library containing 2.19 × 108 independent clones was constructed by the one-step assembly and rapid electro-transformation. The S-Library was screened against various targets (Nb G8, fusion protein of Nb G8 and green fluorescent protein, bovine serum albumin, ovalbumin, and acetylcholinesterase). In comparison, a naïve library (N-Library) from the source of 13 healthy animals was constructed and screened against the same targets as the S-Library. Binders were isolated from both S-Library and N-Library. The dynamic affinity was evaluated by the biolayer interferometry. The data confirms that the feature of the Nb repertoire is conducive to reducing the complexity of library design, thus allowing the S-Library to be built on conventional reagents and primers.

A combinatorial strategy for HRV 3C protease engineering to achieve the N-terminal free cleavage

Human rhinovirus 3C protease (HRV 3CP) has a high specificity against the substrate of LEVLFQ↓G at P1′ site, which plays an important role in biotechnology and academia as a fusion tag removal tool. However, a non-ignorable limitation is that an extra residue of Gly would remain at the N terminus of the recombinant target protein after cleavage with HRV 3CP, thus potentially causing protein mis-functionality or immunogenicity. Here, we developed a combinatorial strategy by integrating structure-guided library design and high-throughput screening of eYESS approach for HRV 3CP engineering to expand its P1′ specificity. Finally, a C3 variant was obtained, exhibiting a broad substrate P1′ specificity to recognize 20 different amino acids with the highest activity against LEVLFQ↓M (kcat/KM = 3.72 ± 0.04 mM−1∙s−1). Further biochemical and NGS-mediated substrate profiling analysis showed that C3 variant still kept its substrate stringency at P1 site and good residue tolerance at P2′ site, but with an expanded P1′ specificity. Structural simulation of C3 indicated a reconstructed S1′ binding pocket as well as new interactions with the substrates. Overall, our studies here prompt not only the practical applications and understanding of substrate recognition mechanisms of HRV 3CP, also provide new tools for other enzyme engineering.

Cyclic β2,3-amino acids improve the serum stability of macrocyclic peptide inhibitors targeting the SARS-CoV-2 main protease.

Due to their constrained conformations, cyclic β2,3-amino acids (cβAA) are key building blocks that can fold peptides into compact and rigid structures, improving peptidase resistance and binding affinity to target proteins, due to their constrained conformations. Although the translation efficiency of cβAAs is generally low, our engineered tRNA, referred to as tRNAPro1E2, enabled efficient incorporation of cβAAs into peptide libraries using the flexible in vitro translation (FIT) system. Here we report on the design and application of a macrocyclic peptide library incorporating 3 kinds of cβAAs: (1R,2S)-2-aminocyclopentane carboxylic acid (β1), (1S,2S)-2-aminocyclohexane carboxylic acid (β2), and (1R,2R)-2-aminocyclopentane carboxylic acid. This library was applied to an in vitro selection against the SARS-CoV-2 main protease (Mpro). The resultant peptides, BM3 and BM7, bearing one β2 and two β1, exhibited potent inhibitory activities with IC50 values of 40 and 20 nM, respectively. BM3 and BM7 also showed remarkable serum stability with half-lives of 48 and >168 h, respectively. Notably, BM3A and BM7A, wherein the cβAAs were substituted with alanine, lost their inhibitory activities against Mpro and displayed substantially shorter serum half-lives. This observation underscores the significant contribution of cβAA to the activity and stability of peptides. Overall, our results highlight the potential of cβAA in generating potent and highly stable macrocyclic peptides with drug-like properties.

Repurposing university library spaces for improved learning satisfaction: The moderating role of organizational size

This paper investigates the moderating influence of library size on the relationship between library space attributes and learning satisfaction. Employing a quantitative methodology, a sample of 196 university library users in Ghana was selected to investigate the perceived impact of repurposed library spaces on learning satisfaction. The author conducted an empirical analysis to examine how organizational size (the total number of workers at a particular location) moderates the association between library space attributes (including access and linkages [physical location and proximity to campus resources], usage patterns [highlights the hours when users are most active and displays when a specific app is utilized during the day], sociability [the propensity and corresponding abilities to look for friendship, interact with others, and take part in social activities], and comfort [a state of physically ease and freedom from pain or constraint]) and the learning satisfaction of users. The research, administered through a closed-ended questionnaire, underscored the significant influence of access and linkages, usage patterns, sociability, and the physical environment on users’ satisfaction levels. These four library space attributes together accounted for 13.1% of the variance in learning satisfaction, according to a multiple regression study conducted with SPSS version 27. Nevertheless, moderation analysis showed that there was no statistically significant relationship (p = 0.3370) between the characteristics of the library space and learning satisfaction through organizational size. The paper recommends adaptations to library designs to better align with the evolving learning needs of university library users in Ghana. A notable suggestion is the transformation of university libraries into dynamic physical spaces known as "learning commons" on campuses.

Exploiting Vector Pattern Diversity of Molecular Scaffolds for Cheminformatics Tasks in Drug Discovery.

Chemical diversity is challenging to describe objectively. Despite this, various notions of chemical diversity are used throughout the medicinal chemistry optimization process in drug discovery. In this work, we show the usefulness of considering exploited vectors during different phases of the drug design process to provide a quantitative and objective description of chemical diversity. We have developed a concise and fast approach to enumerate and analyze the exploited vector patterns (EVPs) of molecular compound series, which can then be used in archetypal compound selection tasks, from hit matter identification to hit expansion and lead optimization. We first show that EVPs can be used to assess the progressibility of compounds in a fragment library design exercise. By considering EVPs, we then show how a set of compounds can be prioritized for hit expansion using EVP-based, customizable diversity sampling approaches, reducing the time taken and mitigating human biases. We also show that EVPs are a useful tool to analyze SAR data, offering the chance to uncover correlations between different vectors without predetermining the molecular scaffold structures. The codes used to perform these tasks are presented as easy-to-use Jupyter notebooks, which can be readily adapted for further related tasks.

Design and Diversity Analysis of Chemical Libraries in Drug Discovery.

Chemical libraries and compound data sets are among the main inputs to start the drug discovery process at universities, research institutes, and the pharmaceutical industry. The approach used in the design of compound libraries, the chemical information they possess, and the representation of structures, play a fundamental role in the development of studies: chemoinformatics, food informatics, in silico pharmacokinetics, computational toxicology, bioinformatics, and molecular modeling to generate computational hits that will continue the optimization process of drug candidates. The prospects for growth in drug discovery and development processes in chemical, biotechnological, and pharmaceutical companies began a few years ago by integrating computational tools with artificial intelligence methodologies. It is anticipated that it will increase the number of drugs approved by regulatory agencies shortly.

The Construction of New Forms of Textbooks and Exploration of Smart Teaching Models in the Perspective of Digital Education Transformation

Currently, digitalization is leading a new wave of educational reform and innovation, giving birth to new forms of digital education, which will continue to have a profound impact on the development of education. This article is based on the "Chaoxing Learning Pass" online platform, exploring new forms of textbook construction and smart classroom models, promoting the integration of digital teaching resources with twin technology, modular design of dynamic textbook project library and smart teaching implementation, as well as the construction of a diversified online evaluation system. It stimulates students' interest in learning, enhances their knowledge literacy and practical skills in industrial robot technology, and achieves good practical teaching results.

Exponential Combination of a and e/g Intracellular Peptide Libraries Identifies a Selective ATF3 Inhibitor.

Activating transcription factor 3 (ATF3) is an activation transcription factor/cyclic adenosine monophosphate (cAMP) responsive element-binding (CREB) protein family member. It is recognized as an important regulator of cancer progression by repressing expression of key inflammatory factors such as interferon-γ and chemokine (C-C motif) ligand 4 (CCL4). Here, we describe a novel library screening approach that probes individual leucine zipper components before combining them to search exponentially larger sequence spaces not normally accessible to intracellular screening. To do so, we employ two individual semirational library design approaches and screen using a protein-fragment complementation assay (PCA). First, a 248,832-member library explored 12 amino acid positions at all five a positions to identify those that provided improved binding, with all e/g positions fixed as Q, placing selection pressure onto the library options provided. Next, a 59,049-member library probed all ten e/g positions with 3 options. Similarly, during e/g library screening, a positions were locked into a generically bindable sequence pattern (AIAIA), weakly favoring leucine zipper formation, while placing selection pressure onto e/g options provided. The combined a/e/g library represents ∼14.7 billion members, with the resulting peptide, ATF3W_aeg, binding ATF3 with high affinity (Tm = 60 °C; Kd = 151 nM) while strongly disfavoring homodimerization. Moreover, ATF3W_aeg is notably improved over component PCA hits, with target specificity found to be driven predominantly by electrostatic interactions. The combined a/e/g exponential library screening approach provides a robust, accelerated platform for exploring larger peptide libraries, toward derivation of potent yet selective antagonists that avoid homoassociation to provide new insight into rational peptide design.