Library Members Research Articles

Fuel-Driven Dynamic Combinatorial Peptide Libraries.

Dynamic combinatorial chemistry (DCC) creates libraries of molecules that are constantly interchanging in a dynamic combinatorial library. When a library member self-assembles, it can displace the equilibria, leading to emergent phenomena like its selection or even its replication. However, such dynamic combinatorial libraries typically operate in or close to equilibrium. This work introduces a new dynamic combinatorial chemistry fueled by a catalytic reaction cycle that forms transient, out-of-equilibrium peptide-based macrocycles. The products in this library exist out of equilibrium at the expense of fuel and are thus regulated by kinetics and thermodynamics. By creating a chemically fueled dynamic combinatorial library with the vast structural space of amino acids, we explored the liquid-liquid phase separation behavior of the library members. The study advances DCCs by showing that peptide structures can be engineered to control the dynamic library's behavior. The work paves the way for creating novel, tunable material systems that exhibit emergent behavior reminiscent of biological systems. These findings have implications for the development of new materials and for understanding life's chemistry.

Developing Catalysts for the Hydrolysis of Glycosidic Bonds in Oligosaccharides Using a Spectrophotometric Screening Assay.

In a proof-of-concept study, a method for the empirical design of polyacrylate gel catalysts with the ability to cleave 1→4 α-glycosidic bonds in di- and trisaccharides was elaborated. The study included the synthesis of a 300-gel member library based on two different cross-linkers and 10 acrylate monomers, identification of monomodal gels by dynamic light scattering, and a 96-well plate spectrophotometric screening assay to monitor the hydrolysis of chromophore-free maltose into glucose units. The composition of the matrix of the most efficient catalysts in the library was found to enable CH-π, hydrophobic, and H-bond accepting interactions during the hydrolysis as typically seen in glycosylases. The same gel catalysts allowed the hydrolysis of the trisaccharide maltotriose with a catalytic proficiency of 2 × 106 indicating transition state stabilization during the hydrolysis of 5 × 10-7. The results place the developed gels among the most efficient catalysts developed for the hydrolysis of natural saccharides. The elaborated strategy may lead to catalysts that can transform polysaccharides into valuable synthons in the near future.

Fuel‐Driven Dynamic Combinatorial Peptide Libraries

Dynamic combinatorial chemistry (DCC) creates libraries of molecules that are constantly interchanging in a dynamic combinatorial library. When a library member self‐assembles, it can displace the equilibria, leading to emergent phenomena like its selection or even its replication. However, such dynamic combinatorial libraries typically operate in or close to equilibrium. This work introduces a new dynamic combinatorial chemistry fueled by a catalytic reaction cycle that forms transient, out‐of‐equilibrium peptide‐based macrocycles. The products in this library exist out of equilibrium at the expense of fuel and are thus regulated by kinetics and thermodynamics. By creating a chemically fueled dynamic combinatorial library with the vast structural space of amino acids, we explored the liquid‐liquid phase separation behavior of the library members. The study advances DCCs by showing that peptide structures can be engineered to control the dynamic library's behavior. The work paves the way for creating novel, tunable material systems that exhibit emergent behavior reminiscent of biological systems. These findings have implications for the development of new materials and for understanding life's chemistry.

“The changing same” of whiteness in the US LIS academy: a cathartic testimonial from BIPOC faculty scholars

PurposeThere is little to no empirical research on the phenomenon of ways in which the racism of whiteness transpires within the faculties and classrooms of US-based ALA-accredited library and information science (LIS) education programs. We do have scholars publishing meaningful work exploring diversity-equity-inclusion topics and initiatives to evolve the LIS discourse on these issues (Honma, 2005; Chancellor, 2019; De LaRosa et al., 2021; Gibson, 2019; Mehra et al., 2023; Colón-Aguirre et al., 2022; Hands, 2022). This research substantiates the conceptual research that exists by empirically exposing the ways in which the racism of whiteness functions at the interpersonal level of work culture in LIS programs (i.e. the academy) in the US.Design/methodology/approachAdapting Baima and Sude’s (2020) modified Delphi Method, a focus group of 13 BIPOC (Black, Indigenous, and People of Color) library and information science faculty members in the United States were recruited to participate in a one-time 60-min virtual Zoom session. Participants were engaged in three iterative rounds of reflective inquiry to reach a consensus of experience. The study design was embedded with critical race theory-based (CRT) ethnographic methods such as testimony (counterstorytelling), collective affirmation (shared narratives), and silence.FindingsBIPOC LIS faculty (tenure-track and tenured) have similar ideas about whiteness and how it is operationalized as micro- and macro-aggressions in the LIS academic workplace, most significantly inside the classroom. The experience of whiteness was prevalent among all study participants in two areas: workplace meetings with faculty colleagues and classroom sessions (face-to-face and online) with students.Originality/valueThe findings offer empirical evidence to support the prolific conceptual literature in LIS discourse concerning ways in which critical race theory (CRT) interrogates LIS’s socio-professional injustices and inequities (e.g. Gibson et al., 2018; Stauffer, 2020; Leung and Lopez-McKnight, 2021; Jennings and Kinzer, 2022; Snow and Dunbar, 2022). There remains a dearth of empirical research that reports how whiteness is reproduced in the practices, knowledge, and resources that make up the ethos of the LIS faculty meeting and classroom. Documenting the testimonies of BIPOC LIS faculty solidifies the existence of whiteness as a toxic reality in the LIS academy.

Permutational Encoding Strategy Accelerates HIT Validation from Single-Stranded DNA-Encoded Libraries.

DNA-Encoded Libraries (DELs) allow the parallel screening of millions of compounds for various applications, including de novo discovery or affinity maturation campaigns. However, library construction and HIT resynthesis can be cumbersome, especially when library members present an unknown stereochemistry. We introduce a permutational encoding strategy suitable for the construction of highly pure single-stranded single-pharmacophore DELs, designed to distinguish isomers at the sequencing level (e.g., stereoisomers, regio-isomers, and peptide sequences). This approach was validated by synthesizing a mock 921,600-member 4-amino-proline single-stranded DEL ("DEL1"). While screening DEL1 against different targets, high-throughput sequencing results showed selective enrichment of the most potent stereoisomers, with enrichment factors that outperform conventional encoding strategies. The versatility of our methodology was additionally validated by encoding 24 scaffolds derived from different permutations of the amino acid sequence of a previously described cyclic peptide targeting Fibroblast Activation Protein (FAP-2286). The resulting library ("DEL2") was interrogated against human FAP, showing selective enrichment of five cyclic peptides. We observed a direct correlation between enrichment factors and on-DNA binding affinities. The presented encoding methodology accelerates drug discovery by facilitating library synthesis and streamlining HIT resynthesis while enhancing enrichment factors at the DEL sequencing level. This facilitates the identification of HIT candidates prior to medicinal chemistry and affinity maturation campaigns.

Synthesis of Mesylated and Tosylated α-Hydroxy-Benzylphosphonates; Their Reactivity and Cytostatic Activity.

α-Hydroxyphosphonates and their acylated and phosphorylated derivatives may be of significant biological activity including cytotoxic effects. To extend the pool of the potentially bioactive species, new methane- and arenesulfonyloxyphosphonates were synthesized by the sulfonylation of differently substituted α-hydroxy-benzylphosphonates using methanesulfonyl chloride or p-toluenesulfonyl chloride at 25 °C in the presence of triethylamine in toluene. The new sulfonyl derivatives were obtained in 54-80% yields. In the case of the 4- or 2-methoxy substituent in the aromatic ring, surprisingly the corresponding α-chlorophosphonates were the exclusive products, whose formation was explained assuming a quinoid intermediate and supported by theoretical calculations. With a 3-methoxyphenyl substituent, the expected mesylation of the hydroxy group took place. Attempted alcoholyses of the diethyl α-methanesulfonyloxy-benzylphosphonates with different substituents in the benzyl ring at ∼140 °C in the presence of triethylamine under microwave irradiation left the P-function intact under the conditions applied, instead, the mesyloxy group was substituted by an alkoxy unit in a selective new reaction. The α-alkoxy-benzylphosphonates were isolated in 60-77% yields. While α-chloro- or α-bromo-benzylphosphonates proved to be rather inefficient in the Michaelis-Arbuzov reaction with triethyl phosphite, according to a new possibility, the α-methansulfonyloxy-benzylphosphonates underwent an efficient Arbuzov fission using the phosphite in excess at 135 °C. The arylmethylenebisphosphonates were obtained in yields of 76-81%. Bioactivity studies with the members of the phosphonate library revealed pronounced in vitro cytostatic effect of the α-hydroxy- and α-mesyloxy-3,5-di-tert-butylbenzylphosphonates on human breast carcinoma cell culture with IC50 values of 16.4 and 28.0 μM, respectively. The mesyloxy species was also cytostatic on melanoma cells (IC50 = 34.9).

Highly pure DNA-encoded chemical libraries by dual-linker solid-phase synthesis.

The first drugs discovered using DNA-encoded chemical library (DEL) screens have entered late-stage clinical development. However, DEL technology as a whole still suffers from poor chemical purity resulting in suboptimal performance. In this work, we report a technique to overcome this issue through self-purifying release of the DEL after magnetic bead-based synthesis. Both the first and last building blocks of each assembled library member were linked to the beads by tethers that could be cleaved by mutually orthogonal chemistry. Sequential cleavage of the first and last tether, with washing in between, ensured that the final library comprises only the fully complete compounds. The outstanding purity attained by this approach enables a direct correlation of chemical display and encoding, allows for an increased chemical reaction scope, and facilitates the use of more diversity elements while achieving greatly improved signal-to-noise ratios in selections.

LIBRARY MANAGEMENT SYSTEM

Abstract : The Library Management System (LMS) is a software application designed to handle the basic operations of a library. The primary objective of the LMS is to provide a user-friendly interface that automates the management of books, members, and transactions, thereby increasing efficiency and reducing the workload of library staff. The system is designed to perform various tasks such as book cataloging, member registration, book issuing, returning, and tracking due dates. It includes modules for adding new books to the inventory, updating book information, and removing books from the catalog. For members, the system allows registration, updating personal information, and tracking borrowing history. The LMS incorporates a robust search functionality that enables users to quickly find books based on various criteria such as title, author, genre, and ISBN. Additionally, it supports generating reports on library usage, overdue books, and member activity, which can help in decision-making and improving library services. Security features are embedded in the system to ensure data integrity and prevent unauthorized access. The LMS provides different access levels for administrators, staff, and members, each with specific permissions to ensure that users can only access functions relevant to their roles. IndexTerms – Management system, Library management, Library, Library Management System.

Top IT Challenges in ARL Libraries

The practice of information technology (IT) in academic libraries is changing rapidly, not only with new and evolving developments in the technologies themselves but also with the organization and management of IT at both the library and institution levels. This study presents the results of an online survey of Association of Research Libraries (ARL) academic library members to identify the biggest challenges they perceive in the area of information technology organization and management. This article compares their responses with challenges reported in earlier studies to identify new and changing trends as well as ongoing challenges that remain.

Structural and Functional Analyses of Inhibition of Human Dihydroorotate Dehydrogenase by Antiviral Furocoumavirin.

Natural products are important sources of seed compounds for drug discovery. However, it has become difficult in recent years to discover new compounds with valuable pharmacological activities. On the other hand, among the vast number of natural products that have been isolated so far, a considerable number of compounds with specific biological activities are thought to be overlooked in screening that uses biological activity as an index. Therefore, it is conceivable that such overlooked useful compounds may be found by screening compound libraries that have been amassed previously through specific assays. Previously, NPD723, a member of the Natural Products Depository library comprised of a mixture of natural and non-natural products developed at RIKEN, and its metabolite H-006 were found to inhibit growth of various cancer cells at low nanomolar half-maximal inhibitory concentration. Subsequent analysis revealed that H-006 strongly inhibited human dihydroorotate dehydrogenase (DHODH), the rate-limiting enzyme in the de novo pyrimidine biosynthetic pathway. Here, we elucidated the crystal structure of the DHODH-flavin mononucleotide-orotic acid-H-006 complex at 1.7 Å resolution to determine that furocoumavirin, the S-enantiomer of H-006, was the actual inhibitor. The overall mode of interaction of furocoumavirin with the inhibitor binding pocket was similar to that described for previously reported tight-binding inhibitors. However, the structural information together with kinetic characterizations of site-specific mutants identified key unique features that are considered to contribute to the sub-nanomolar inhibition of DHODH by furocoumavirin. Our finding identified new chemical features that could improve the design of human DHODH inhibitors.

Ultrahigh Throughput Evolution of Tryptophan Synthase in Droplets via an Aptamer Sensor.

Tryptophan synthase catalyzes the synthesis of a wide array of noncanonical amino acids and is an attractive target for directed evolution. Droplet microfluidics offers an ultrahigh throughput approach to directed evolution (up to 107 experiments per day), enabling the search for biocatalysts in wider regions of sequence space with reagent consumption minimized to the picoliter volume (per library member). While the majority of screening campaigns in this format on record relied on an optically active reaction product, a new assay is needed for tryptophan synthase. Tryptophan is not fluorogenic in the visible light spectrum and thus falls outside the scope of conventional droplet microfluidic readouts, which are incompatible with UV light detection at high throughput. Here, we engineer a tryptophan DNA aptamer into a sensor to quantitatively report on tryptophan production in droplets. The utility of the sensor was validated by identifying five-fold improved tryptophan synthases from ∼100,000 protein variants. More generally, this work establishes the use of DNA-aptamer sensors with a fluorogenic read-out in widening the scope of droplet microfluidic evolution.

PENERAPAN METODE ASOSIASI PADA ANALISA POLA PEMINJAMAN BUKU PERPUSTAKAAN

The library produces a lot of book loan transaction data every day, but the data has not been maximally utilized due to the limited knowledge of the data, therefore the librarian cannot provide the right book recommendations for readers. The research aims to analyze book loan data by applying the Knowledge Discovery in Database (KDD) method. The research stages are observation and interviews, data selection and data preprocessing, data transformation. Data processing using the apriori algorithm association rule mining approach to provide an overview in seeing the pattern of book loan transactions. This is to provide book recommendations that match the reading interests of library members, so that it can become a reference in the layout of books on the shelf according to the results of the rules formed. The book loan transaction data used is the September period of 2023, the implementation uses the rapidminer application to find association rules. The results obtained as many as 77 rule recommendations with the highest support value of 10.7%, the highest confidence value of 100% and the highest lift value of 14. The rule formed is that if a library member borrows a book by Dale Carneige, the chances that the library member will also borrow a book by George Orwel are 100%. The results obtained can be a reference for the library to provide book recommendations to readers, maintain the availability of book stock and arrange the placement of these books on adjacent shelves.

Positive epistasis drives clavulanic acid resistance in double mutant libraries of BlaC β-lactamase

Phenotypic effects of mutations are highly dependent on the genetic backgrounds in which they occur, due to epistatic effects. To test how easily the loss of enzyme activity can be compensated for, we screen mutant libraries of BlaC, a β-lactamase from Mycobacterium tuberculosis, for fitness in the presence of carbenicillin and the inhibitor clavulanic acid. Using a semi-rational approach and deep sequencing, we prepare four double-site saturation libraries and determine the relative fitness effect for 1534/1540 (99.6%) of the unique library members at two temperatures. Each library comprises variants of a residue known to be relevant for clavulanic acid resistance as well as residue 105, which regulates access to the active site. Variants with greatly improved fitness were identified within each library, demonstrating that compensatory mutations for loss of activity can be readily found. In most cases, the fittest variants are a result of positive epistasis, indicating strong synergistic effects between the chosen residue pairs. Our study sheds light on a role of epistasis in the evolution of functional residues and underlines the highly adaptive potential of BlaC.

Reading against Reform: The Bristol Library Society and the Intellectual Culture of Bristol's Elections in 1812*

AbstractThis article pioneers a new methodological approach to the study of electoral politics by combining an analysis of the politics of reading, library association and the reading habits of electors in an English urban constituency in the early 19th century. By integrating an examination of reading practices and intellectual context into our analysis of electoral contests, political history scholars can go further in their examination of the unreformed electoral system and attempt to gauge the motivations behind voting habits and partisan identification in this period. Using electoral voting data and the records of an urban subscription library, this article explores the interrelation between the Bristol Library Society and Bristol's electoral politics, as well as conducting an analysis of which books were being borrowed and read by electors in a politically tumultuous year. Although few in number compared with the total size of Bristol's electorate, Bristol Library members were among some of the most politically and culturally influential individuals in Bristol society and were active participants in electoral contests in the city, either as candidates, campaigners, civic officials or voters. An analysis of their voting habits reveals that the library's membership reflected the Tory political hegemony that became pronounced in the city's civic politics. Moreover, an analysis of their reading habits in 1812 reveals an interest in political texts that were conservative and anti‐Gallic in tone, that were representative of the political climate in Bristol in 1812, and which contributed to the defeat of candidates for reform in its electoral contests.

The Influence of Communication Strategy on User Satisfaction at the Medan State Polytechnic Library

The title of this research was The Influence of Communication Strategy and Prime Service on Library Members’ Satisfaction at the Library of Politeknik Negeri Medan. The research used the theory of satisfaction. Kotler (2014) points out that there are two theories of satisfaction: theory of performance expectation and theory of cognitive inappropriateness. Theory of performance expectation states that consumer satisfaction is the function of consumers’ expectation of the result. If the result is in accordance with what has been expected, consumers will be satisfied, if it exceeds what has been expected, they will be more satisfied, but if it is not in accordance with what has been expected, they will be dissatisfied. The population was 5,994 members of the library, and 98 of them were used as the samples, taken by using Slovin formula. The data were gathered by using questionnaires and conducting documentation and observation. The result of the research showed that the factors of communication strategy and prime service had positive and significant influence on library members’ satisfaction which indicated that the better the communication strategy and the prime service, the higher the library members’ level of satisfaction.

The transaction analysis of loan and usage of information resources by library members: A case study of public libraries in Ilam province

The transaction analysis of loan and usage of information resources by library members: A case study of public libraries in Ilam province

Rancang Bangun Alat Pengembalian Buku Perpustakaan Secara Mandiri Berbasis Single Board Computer

the process of borrowing and returning library books usually requires a librarian to go through this process, of course this requirement can cause delays in returning books due to library holidays and the difference in free hours from the library and library members. so this research aims to make it easy for library members to be able to return books independently using a storage box that can be done by the system. in this book return box using a raspberry pi 3b+ as a data processing center and using the pi camera to capture the book cover made on the book return box. the security system in this return box uses a selenoid door lock as an automatic door lock which will be routed by a relay and uses rfid as the identity of books, members and librarians. in this study the system can store and return books using the K-Nearest Neighbor (KNN) method with an accuracy of 95% with a processing time of 6.9s

Streamlined Protein-Protein Interface Loop Mimicry.

Cyclic peptides comprising endocyclic organic fragments, "cyclo-organopeptides", can be probes for perturbing protein-protein interactions (PPIs). Finding loop mimics is difficult because of high conformational variability amongst targets. Backbone Matching (BM), introduced here, helps solve this problem in the illustrative cases by facilitating efficient evaluation of virtual cyclo-organopeptide core-structure libraries. Thus, 86 rigid organic fragments were selected to build a library of 602 cyclo-organopeptides comprising Ala and organic parts: "cyclo-{-(Ala)n -organo-}". The central hypothesis is "hit" library members have accessible low energy conformers corresponding to backbone structures of target protein loops, while library members which cannot attain this conformation are probably unworthy of further evaluation. BM thereby prioritizes candidate loop mimics, so that less than 10 cyclo-organopeptides are needed to be prepared to find leads for two illustrative PPIs: iNOS ⋅ SPSB2, and uPA ⋅ uPAR.

Streamlined Protein‐Protein Interface Loop Mimicry

AbstractCyclic peptides comprising endocyclic organic fragments, “cyclo‐organopeptides”, can be probes for perturbing protein‐protein interactions (PPIs). Finding loop mimics is difficult because of high conformational variability amongst targets. Backbone Matching (BM), introduced here, helps solve this problem in the illustrative cases by facilitating efficient evaluation of virtual cyclo‐organopeptide core‐structure libraries. Thus, 86 rigid organic fragments were selected to build a library of 602 cyclo‐organopeptides comprising Ala and organic parts: “cyclo‐{‐(Ala)n‐organo‐}”. The central hypothesis is “hit” library members have accessible low energy conformers corresponding to backbone structures of target protein loops, while library members which cannot attain this conformation are probably unworthy of further evaluation. BM thereby prioritizes candidate loop mimics, so that less than 10 cyclo‐organopeptides are needed to be prepared to find leads for two illustrative PPIs: iNOS ⋅ SPSB2, and uPA ⋅ uPAR.

Rancang Bangun Sistem Informasi Perpustakaan Pada SDN 21 Desa Sesap

With the rapid development of information technology, it has a very important role in various fields, one of which is education. The library information system is a system that is very useful for managing, making things easier for staff and storing library book collections using the system. SD Negeri 21 Sesap Village has a library that stores various kinds of learning books, but the service is still done manually or still in the form of bookkeeping, so it is prone to errors, for example library member data, book data and borrower data. In this research, interview and literature study methods were used, and the programming language used was Hypertext Processor (PHP) and the database used MySQL. The aim of this paper is to design a computerized library information system at SD Negeri 21 Sesap Village to make it easier to manage book data and anticipate errors that occur in library management at SD Negeri 21 Sesap Village.