Complete Library Research Articles

A Solution to Design Semi-static Null Convention Logic Cell Libraries

The Null Convention Logic (NCL) based asynchronous circuits have eliminated the disadvantages of the synchronous circuits, including noise, glitches, clock skew, power, and electromagnetic interference. However, using NCL based asynchronous designs was not easy for students and researchers because of the lack of standard NCL cell libraries. This paper proposes a solution to design a semi-static NCL cell library used to synthesize NCL based asynchronous designs. This solution will help researchers save time and effort to approach a new method. In this work, NCL cells are designed based on the Process Design Kit 45nm technology. They are simulated at the different corners with the Ocean script and Electronic Design Automation (EDA) environment to extract the timing models and the power models. These models are used to generate a *.lib file, which is converted to a *.db file by the Design Compiler tool to form a complete library of 27 cells. In addition, we synthesize the NCL based full adders to illustrate the success of the proposed library and compare our synthesis results with the results of the other authors. The comparison results indicate that power and delay are improved significantly.

A Systematic Review of the Impact of Wildfires on Sleep Disturbances.

Wildfires present a serious risk to humans as well as to the environment. Wildfires cause loss of lives, economic losses, expose people to personal as well as collective trauma, and compromise the mental health of survivors. Sleep disturbances are highly prevalent following a traumatic event; however, their prevalence is not well established amongst those confronted by natural disasters such as wildfires. The aim of this systematic review is to synthesise the empirical findings pertaining to wildfires and the prevalence of sleep disturbances in the general community affected by this natural disaster. We searched EBSCO, PsychINFO, Medline, SpringerLink, CINAHL Complete, EMBASE, PubMed, Scopus and Cochrane Library between January 2012 and March 2021. Five studies met the inclusion criteria. Findings from this systematic review suggest that sleep disturbances, assessed one to ten months following the fires, are highly prevalent in wildfire survivors, with insomnia (ranging between 63–72.5%) and nightmares (ranging between 33.3–46.5%), being the most prevalent sleep disturbances reported in this cohort. Results also highlight the significant associations between sleep disturbances and post-traumatic symptoms following the trauma of wildfires. There is a possible link between sleep disturbance prevalence, severity of, and proximity to fires.

A spectral library for laser-induced fluorescence analysis as a tool for rare earth element identification

Abstract. With the recurring interest in rare earth elements (REEs), laser-induced fluorescence (LiF) may provide a powerful tool for their rapid and accurate identification at different stages along their value chain. Applications to natural materials such as minerals and rocks could complement the spectroscopy-based toolkit for innovative, non-invasive exploration technologies. However, the diagnostic assignment of detected emission lines to individual REEs remains challenging because of the complex composition of natural rocks in which they can be found. The resulting mixed spectra and the large amount of data generated demand automated approaches of data evaluation, especially in mapping applications such as drill core scanning. LiF reference data provide the solution for robust REE identification, yet they usually remain in the form of tables of published emission lines. We show that a complete reference spectra library could open manifold options for innovative automated analysis. We present a library of high-resolution LiF reference spectra using the Smithsonian rare earth phosphate standards for electron microprobe analysis. We employ three standard laser wavelengths (325, 442, 532 nm) to record representative spectra in the UV-visible to near-infrared spectral range (340–1080 nm). Excitation at all three laser wavelengths yielded characteristic spectra with distinct REE-related emission lines for EuPO4, TbPO4, DyPO4 and YbPO4. In the other samples, the high-energy excitation at 325 nm caused unspecific, broad-band defect emissions. Here, lower-energy laser excitation is shown to be successful for suppressing non-REE-related emission. At 442 nm excitation, REE reference spectra depict the diagnostic emission lines of PrPO4, SmPO4 and ErPO4. For NdPO4 and HoPO4 the most efficient excitation was achieved with 532 nm. Our results emphasise the possibility of selective REE excitation by changing the excitation wavelength according to the suitable conditions for individual REEs. Our reference spectra provide a database for the transparent and reproducible evaluation of REE-bearing rocks. The LiF spectral library is available at zenodo.org and the registered DOI https://doi.org/10.5281/zenodo.4054606 (Fuchs et al., 2020). Primarily addressing the raw material exploration sector, it aids particularly the development of advanced data processing routines for LiF analysis but can also support further research on the REE luminescence in natural rocks or artificial compounds. It gives access to traceable data for the comparison of emission line positions, emission line intensity ratios and splitting into emission line sub-levels or can be used as reference or training data for automated approaches of component assignment.

Analysis on Challenges and Responses of Library and Information Service in Digital Information Environment

In the context of the era of digital information, library and information services can provide readers with better, more diverse and more convenient services. While digital information promotes the perfect development of library and information services, it also faces many challenges in its services. Based on this, this article applies literature research and other methods to analyze the many development challenges faced by library and information services in the digital information environment, and explores strategies and specific methods for adapting to build a more complete library and information service system and improve its service quality. To promote the healthy and long-term development of the library industry.

Binding affinity landscapes constrain the evolution of broadly neutralizing anti-influenza antibodies.

Over the past two decades, several broadly neutralizing antibodies (bnAbs) that confer protection against diverse influenza strains have been isolated. Structural and biochemical characterization of these bnAbs has provided molecular insight into how they bind distinct antigens. However, our understanding of the evolutionary pathways leading to bnAbs, and thus how best to elicit them, remains limited. Here, we measure equilibrium dissociation constants of combinatorially complete mutational libraries for two naturally isolated influenza bnAbs (CR9114, 16 heavy-chain mutations; CR6261, 11 heavy-chain mutations), reconstructing all possible evolutionary intermediates back to the unmutated germline sequences. We find that these two libraries exhibit strikingly different patterns of breadth: while many variants of CR6261 display moderate affinity to diverse antigens, those of CR9114 display appreciable affinity only in specific, nested combinations. By examining the extensive pairwise and higher order epistasis between mutations, we find key sites with strong synergistic interactions that are highly similar across antigens for CR6261 and different for CR9114. Together, these features of the binding affinity landscapes strongly favor sequential acquisition of affinity to diverse antigens for CR9114, while the acquisition of breadth to more similar antigens for CR6261 is less constrained. These results, if generalizable to other bnAbs, may explain the molecular basis for the widespread observation that sequential exposure favors greater breadth, and such mechanistic insight will be essential for predicting and eliciting broadly protective immune responses.

Complete cysteine-scanning mutagenesis of the Salmonella typhimurium melibiose permease

The melibiose permease of Salmonella typhimurium (MelBSt) catalyzes the stoichiometric symport of galactopyranoside with a cation (H+, Li+, or Na+) and is a prototype for Na+-coupled major facilitator superfamily (MFS) transporters presenting from bacteria to mammals. X-ray crystal structures of MelBSt have revealed the molecular recognition mechanism for sugar binding; however, understanding of the cation site and symport mechanism is still vague. To further investigate the transport mechanism and conformational dynamics of MelBSt, we generated a complete single-Cys library containing 476 unique mutants by placing a Cys at each position on a functional Cys-less background. Surprisingly, 105 mutants (22%) exhibit poor transport activities (<15% of Cys-less transport), although the expression levels of most mutants were comparable to that of the control. The affected positions are distributed throughout the protein. Helices I and X and transmembrane residues Asp and Tyr are most affected by cysteine replacement, while helix IX, the cytoplasmic middle-loop, and C-terminal tail are least affected. Single-Cys replacements at the major sugar-binding positions (K18, D19, D124, W128, R149, and W342) or at positions important for cation binding (D55, N58, D59, and T121) abolished the Na+-coupled active transport, as expected. We mapped 50 loss-of-function mutants outside of these substrate-binding sites that suffered from defects in protein expression/stability or conformational dynamics. This complete Cys-scanning mutagenesis study indicates that MelBSt is highly susceptible to single-Cys mutations, and this library will be a useful tool for further structural and functional studies to gain insights into the cation-coupled symport mechanism for Na+-coupled MFS transporters.

O-051 Telenursing within fertility

textAberdeen Fertility Centre provides fertility investigation and treatment across the north east, highlands and islands (Orkney & Shetland) of Scotland, which includes rural and remote communities. Whilst the SARS-Cov-2 pandemic has accelerated the delivery of Tele-fertility Nursing, the National Health Service (NHS) in Grampian, Scotland launched both ‘No Delays’ and ‘Near Me’ platforms in 2019 to keep pace with the digital age and with the intention of improving the quality of patient care.No Delays (series of video packages and virtual consultations) has revolutionised clinical pathways, providing individualised patient information from investigation to treatment, permitting email ‘prescription’ of digital postcards (personalised package of short videos introducing members of the team and explaining their role) that explain the fertility journey and management plan in detail, from investigation (ie., tubal evaluation), to treatment (ie., ovulation induction or IVF), and self-administration of medicines.Thereafter, patients receive invitation to virtual ‘Near Me’ consultation which can take place in the comfort of their own home whilst acknowledging flexibility in lifestyle (partner can remotely access consultation from workplace, including overseas).Electronic patient records (EPR’s) provide immediate access to complete, accurate and up to date clinical patient data, which, together with Electronic Consents compliment the tele-nursing experience through a complete library of consent forms, automatically allocated to patient and partner according to treatment type and personal circumstances: information being provided in video format to meet the requirements for informed consent. Forms are completed online, at home or in the ‘virtual’ clinic via computers, tablets or smartphones, with workflow automation tools allowing for digital signature/s. The complete digital package ensures patients have an early understanding of the process, therefore better prepared for face-to-face appointments and ensuring quality care delivered at point of contact.The aims and objectives of ‘Tele-fertility Nursing’ were to: (1) reinforce key information routinely provided at consultation which may not always be understood, (2) meet patient need and lifestyle, (3) increase patient choice, (4) save time and money by reducing unnecessary travel (often complicated by adverse weather conditions from rural communities), (5) avoid unnecessary time off work, and (6) reduce environmental impact of attended appointments (health miles and miles not travelled).Whilst concern remains around the digital interface and nurse/patient relationship, preliminary evaluation of ‘Near Me’ consultations and patient feedback - relative to electronic consent - suggests overall patient satisfaction; the above aims and objectives being met. However, full evaluation of the patient and fertility nurse experience of the ‘digital fertility journey’ is required.

Toward a global DNA barcode reference library of the intolerant nonbiting midge genus Rheocricotopus Brundin, 1956.

Environmental DNA metabarcoding is becoming a predominant tool in biodiversity assessment, as this time‐ and cost‐efficient tactics have the ability to increase monitoring accuracy. As a worldwide distributed genus, Rheocricotopus Brundin, 1956 still does not possess a complete and comprehensive global DNA barcode reference library for biodiversity monitoring. In the present study, we compiled a cytochrome c oxidase subunit 1 (COI) DNA barcode library of Rheocricotopus with 434 barcodes around the world, including 121 newly generated DNA barcodes of 32 morphospecies and 313 public barcodes. Automatic Barcode Gap Discovery (ABGD) was applied on the 434 COI barcodes to provide a comparison between the operational taxonomic units (OTU) number calculated from the Barcode Index Number (BIN) with the “Barcode Gap Analysis” and neighbor‐joining (NJ) tree analysis. Consequently, these 434 COI barcodes were clustered into 78 BINs, including 42 new BINs. ABGD yielded 51 OTUs with a prior intraspecific divergence of Pmax = 7.17%, while NJ tree revealed 52 well‐separated clades. Conservatively, 14 unknown species and one potential synonym were uncovered with reference to COI DNA barcodes. Besides, based on our ecological analysis, we discovered that annual mean temperature and annual precipitation could be considered as key factors associated with distribution of certain members from this genus. Our global DNA barcode reference library of Rheocricotopus provides one fundamental database for accurate species delimitation in Chironomidae taxonomy and facilitates the biodiversity monitoring of aquatic biota.

Abstract 1175: Identification of novel combination therapies with the LSD1 inhibitor SP-2577 (Seclidemstat) in Ewing's Sarcoma using a complete druggable CRISPR library approach

Abstract Introduction: Ewing's Sarcoma (ES) is a rare and aggressive pediatric bone tumor that is driven by a chromosomal translocation and fusion between EWS and FLI1 genes resulting in a chimeric protein. Nearly 85% of ES cases express the EWS/FLI protein which functions as a transcription factor and drives oncogenesis. It has been previously observed in ES patient samples have high levels of the histone lysine specific demethylase 1 (LSD1). LSD1 is recruited by EWS/FLI as a member of the nucleosome remodeling and histone deacetylase (NuRD) complex to repress the critical EWS/FLI targets LOX and TGFBR2. Treatment with the potent LSD1 reversible inhibitor, SP-2577 (Seclidemstat), causes de-repression of these genes and impaired tissue culture cell viability in multiple ES cell lines. In this study we investigated new targeted therapies to use in combination with SP-2577 to help increase the cytotoxicity of the drug within ES cell types. Methods: Synthego® arrayed CRISPR screening platform was used to knock down genes associated with known druggable interactions in the ES cell line SK-N-MC. Genes were knocked down singularly either in the presence/absence of SP-2577. Viability screening was used to determine genes that increased the cytotoxicity of SP-2577. Statistical analysis, z-score, and IPA analysis was performed to investigate correlations between loss of gene effect and LSD1 pathway. Hit-gene validation was performed using siRNA and/or sgRNA knockdown/knockout, and other methods such as qPCR, and western blot assay for protein expression. Results: Arrayed CRISPR screening identified 103 gene deletions that resulted in increased SP-2577 cytotoxicity in SK-N-MC cell line. Among those, the top 19 hits were selected by identifying a FDA approved drug-gene interaction. Two high- interest hits were seen to have significant interaction with the LSD1 pathway: ABL2 and SH2B3. Drug combination treatment of SP-2577 with either Ruxolitinib or Dasatinib in ES cell lines showed high synergy at low dose ratio. Downstream pathways analysis confirmed the efficacy of the drugs combination. Detailed data will be presented. Conclusion: Our data support the validity of the arrayed CRISPR screening to identify new therapeutic strategies in ES, and highlights the potential for Ruxolitinib or Dasatinib treatment in combination with SP-2577 in ES patients. Citation Format: Samuel Sampson, Trason Thode, Mohan Kaadige, Alexis Weston, Serina Ng, Kevin Drenner, Raffaella Soldi, Sunil Sharma. Identification of novel combination therapies with the LSD1 inhibitor SP-2577 (Seclidemstat) in Ewing's Sarcoma using a complete druggable CRISPR library approach [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1175.

Domain-aware meta network for radar HRRP target recognition with missing aspects

Conventional high resolution range profile (HRRP) based radar automatic target recognition (RATR) methods are based on a complete template library assumption. However, such an assumption can barely hold in real world applications since it is difficult to observe target echoes from all aspects, especially for noncooperative targets. To alleviate the target-aspect missing problem, we develop a domain-aware meta network (DOAMN) for HRRP-based RATR. Specifically, the DOAMN first uses a domain-aware (DOM) module to distinguish whether HRRPs come from the seen or unseen target aspects, then a meta network (MNet) is employed to learn a generalized parameter initialization that is able to achieve fast adaptation among target aspects. To enable the proposed DOAMN to be trained in an end-to-end manner, we further present an effective iterative hybrid optimization method. Experiments on simulated HRRP dataset demonstrate the effectiveness and efficiency of the proposed model.

Potentially inappropriate prescribing and its associations with health-related and system-related outcomes in hospitalised older adults: A systematic review and meta-analysis.

AimsTo synthesise associations of potentially inappropriate prescribing (PIP) with health‐related and system‐related outcomes in inpatient hospital settings.MethodsSix electronic databases were searched: Medline Complete, EMBASE, CINAHL, PyscInfo, IPA and Cochrane library. Studies published between 1 January 1991 and 31 January 2021 investigating associations between PIP and health‐related and system‐related outcomes of older adults in hospital settings, were included. A random effects model was employed using the generic inverse variance method to pool risk estimates.ResultsOverall, 63 studies were included. Pooled risk estimates did not show a significant association with all‐cause mortality (adjusted odds ratio [AOR] 1.10, 95% confidence interval [CI] 0.90–1.36; adjusted hazard ratio 1.02, 83% CI 0.90–1.16), and hospital readmission (AOR 1.11, 95% CI 0.76–1.63; adjusted hazard ratio 1.02, 95% CI 0.89–1.18). PIP was associated with 91%, 60% and 26% increased odds of adverse drug event‐related hospital admissions (AOR 1.91, 95% CI 1.21–3.01), functional decline (AOR 1.60, 95% CI 1.28–2.01), and adverse drug reactions and adverse drug events (AOR 1.26, 95% CI 1.11–1.43), respectively. PIP was associated with falls (2/2 studies). The impact of PIP on emergency department visits, length of stay, and health‐related quality of life was inconclusive. Economic cost of PIP reported in 3 studies, comprised various cost estimation methods.ConclusionsPIP was significantly associated with a range of health‐related and system‐related outcomes. It is important to optimise older adults' prescriptions to facilitate improved outcomes of care.

Socio-Physical Transformation towards Sustainable Urban Morphology through Land Readjustment in Indonesia

In the development sector, the need for land is increasing, resulting in the higher land value and land use mismatches. Urban areas have a relatively fixed area, while the need for land continues to increase. Weaknesses in urban management lead to speculation, illegal land use, and slums. Development activities should impact the physical, environmental, economic, and social conditions of the community [29]. The development process often pays little attention to these matters. In the last few decades, we have observed a very rapid social transformation process in urban areas that has changed the morphology of Indonesian cities. This transformation has accelerated after the implementation of regional autonomy in Indonesia since 1999. Land conflicts in urban areas do not end, so it is necessary to consolidate land as an activity to restructure land tenure, land use, and land acquisition to improve environmental quality and preserve natural resources and ecosystems by involving the community to play an active role. This study aims to evaluate the extent to which land readjustment in Indonesia can improve the efficiency and productivity of morphological transformation of urban land use, the extent of community participation, and its alignments to low-income people and their handling of slum areas. This study uses qualitative exploratory research methods and normative juridical approach methods through library studies. It uses the legislative approach, fact approach, and conceptual approach and primary data in the form of interviews to complete library studies. The study results show that land readjustment can improve the efficiency and productivity of morphological transformation of urban land use optimally and it is an effective way that contributes to the spatial planning that is more just, integrated and sustainable.

Do they know it when they see it?: Natural language preferences of undergraduate students for library resources

This study explored the range of undergraduate students’ natural language preferences for library resources when shown verbal and visual representations of those resources. The results indicate little consensus for preferred language although participants generally preferred natural language over library jargon. The majority of participants did not use the same language to describe a resource between the visual and verbal exercises. Furthermore, prior library instruction had no meaningful effect on participants’ language preferences. More research is needed to explore the significance of recurring library instruction on students’ language preferences and if these language preferences impact their ability to complete library research-based tasks.

Challenges in building barcode reference libraries for marine invertebrates exemplified by the genus Prionospio (Annelida: Spionidae)

The completeness of reference libraries is often a limiting factor in the effectiveness of biomonitoring using molecular tools. The fact that these libraries are often built upon Sanger sequencing can create a substantial bias due to poor primer fits and unoptimized lab protocols. Some taxa of marine macroinvertebrates are known to be notoriously difficult to sequence using traditional, PCR-based means, and only about 15% of the known bioindicator species world-wide have publicly available sequences for any genetic marker (Aylagas et al. 2014). The Barcode of Life Data System (BOLD) indicates an amplification rate between 46% and 85% of the barcode region of COI for the most commonly used marine invertebrates that indicate pollution in the North East Atlantic (Capitellidae, Cirratulidae, Dorvilleidae, Spionidae and Tubificidae within Annelida, and Thyasiridae within Mollusca). A currently on-going integrative taxonomic study on Prionospio Malmgren, 1867 (Spionidae, Annelida) exemplifies the extensive issues of utilizing Sanger sequencing on marine invertebrates. The barcode region of COI was attempted amplified using five primer pairs: three designed to be universal for marine invertebrates (Folmer et al. 1994, Geller et al. 2013, Lobo et al. 2013), one specialized on polychaetes (Carr et al. 2011) and one self-designed. In addition, two DNA polymerases were tested (TaKaRa Ex Taq HS and Qiagen HotStarTaq) and three annealing temperatures. Only five sequences of COI were obtained from a total of 255 PCR reactions (2% success rate). Other genetic markers showed better amplification rates: 58% for 16S rDNA, and more than 90% success rates for 28S rDNA and Histone H3. This illustrates the importance of having more than one marker in mind when seeking to complete reference libraries, and the potential effectiveness of a multi-marker approach in molecular biomonitoring surveys. As sequencing costs decrease, utilizing shallow shotgun-based sequencing (genome skimming) on problematic groups such as Prionospio to bypass issues regarding unfit primers is also becoming a viable option.

Discovery of Metastatic Regulators using a Rapid and Quantitative Intravital Chick Chorioallantoic Membrane Model.

Recent advances in cancer research has illustrated the highly complex nature of cancer metastasis. Multiple genes or genes networks have been found to be involved in differentially regulating cancer metastatic cascade genes and gene products dependent on the cancer type, tissue, and individual patient characteristics. These represent potentially important targets for genetic therapeutics and personalized medicine approaches. The development of rapid screening platforms is essential for the identification of these genetic targets. The chick chorioallantoic membrane (CAM) is a highly vascularized, collagen rich membrane located under the eggshell that allows for gas exchange in the developing embryo. Due to the location and vascularization of the CAM, we developed it as an intravital human cancer metastasis model that allows for robust human cancer cell xenografting and real-time imaging of cancer cell interactions with the collagen rich matrix and vasculature. Using this model, a quantitative screening platform was designed for the identification of novel drivers or suppressors of cancer metastasis. We transduced a pool of head and neck HEp3 cancer cells with a complete human genome shRNA gene library, then injected the cells, at low density, into the CAM vasculature. The cells proliferated and formed single-tumor cell colonies. Individual colonies that were unable to invade into the CAM tissue were visible as a compact colony phenotype and excised for identification of the transduced shRNA present in the cells. Images of individual colonies were evaluated for their invasiveness. Multiple rounds of selections were performed to decreases the rate of false positives. Individual, isolated cancer cell clones or newly engineered clones that express genes of interest were subjected to primary tumor formation assay or cancer cell vasculature co-option analysis. In summary we present a rapid screening platform that allows for anti-metastatic target identification and intravital analysis of a dynamic and complex cascade of events.

Service Interoperability System Architecture and Service Extension Method

With the development of power grid, the amount of data and calculation generated by network edge devices is increasing rapidly, which brings the pressure of data analysis and storage, service interoperability and model expansion. Traditional edge cloud collaboration mode uses user-defined model manually, and then downloads the model from the cloud to the edge for execution to expand the model. This method relies heavily on human experience and is difficult to ensure the efficiency of model expansion when the amount of data is large. Based on the analysis of three basic capabilities of service interoperability system, this paper innovatively proposes an automatic construction method of service extension. Firstly, the model is described as a tree structure, and then the model is automatically added from the edge to the cloud as a branch. Finally, a complete industry interoperability model library is formed in the cloud.

Assembling a library of typical surgery video clips to construct a system for assessing the surgical difficulty of laparoscopic cholecystectomy.

To explore best practices for acute cholecystitis, it is necessary to construct a system to assess the difficulty of laparoscopic cholecystectomy (LC) based on intraoperative findings. In this study, multiple evaluators assessed videos of LC to assemble a library of typical video clips for 25 intraoperative findings. We have previously identified 25 items that contribute to surgical difficulty in LC. For each item, roughly 30-second video clips were submitted from videos of LC performed at member institutions. We then selected one typical video from the collected clips based on simple tabulation of the instances of agreement. Inter-rater agreement was assessed with Fleiss's κ and Gwet's agreement coefficient (AC). Except in the case of two assessment items ("edematous change" and "easy bleeding"), κ or AC significantly exceeded 0.5 and the typical videos were judged to be applicable. For the two remaining items, the evaluation was repeated after clarifying the definitions of positive and negative findings. Eventually, they were recognized as typical. The completed video clip library contains 31 clips and is divided into five categories (http://www.jshbps.jp/modules/project/index.php?content_id=13). This clip library may be highly useful in clinical settings as a more objective standard for assessing surgical difficulty in LC.

The Influence of Tianxue (Heavenly Learning) on Chinese Thought in the Seventeenth Century

In the history of ideas in 17th-century China, the “heavenly learning” (tianxue) introduced by Western missionaries, in particularly the Jesuits, was a factor to be reckoned with. Without doubt it provided a fresh input to the development of post-Wang Yangming philosophy and the incubation of new insights in late Ming Neo-Confucianism, and this influence continued until the early Qing dynasty. However, while natural sciences and practical technologies (such as artillery and water conservancy) were well-received as part of the “heavenly learning,” other parts such as the “learning on the principle,” i.e., tenets of the Christian faith, conflicted with Confucianism. Due to the repercussions of the Chinese Rites Controversy in the late years of the Kangxi reign (r. 1661–1722), the public activities of missionaries in China were restricted. And when the Qing imperial court was in the process of compiling the Siku quanshu (Complete Library in Four Branches of Literature), those parts of “heavenly learning” dealing with the Christian faith were screened. To a certain degree this prevented later generations from gaining a proper overview of “heavenly learning.” Another factor that negatively impacted the study of the relationship between “heavenly learning” and Chinese traditional thought in the 17th century was that Christianity in modern China was closely associated with the invasion of imperialism in modern times. But how did the Confucianism from the late Ming to the early Qing period treat “heavenly learning”? This article summarizes the various attitudes of some Confucian scholars towards “heavenly learning” in hope of inciting further academic discussions.

Aqueous ionic liquids redistribute local enzyme stability via long-range perturbation pathways

Ionic liquids (IL) and aqueous ionic liquids (aIL) are attractive (co–)solvents for biocatalysis due to their unique properties. On the other hand, the incubation of enzymes in IL or aIL often reduces enzyme activity. Recent studies proposed various aIL-induced effects to explain the reduction, classified as direct effects, e.g., local dehydration or competitive inhibition, and indirect effects, e.g., structural perturbations or disturbed catalytic site integrity. However, the molecular origin of indirect effects has largely remained elusive. Here we show by multi-μs long molecular dynamics simulations, free energy computations, and rigidity analyses that aIL favorably interact with specific residues of Bacillus subtilis Lipase A (BsLipA) and modify the local structural stability of this model enzyme by inducing long-range perturbations of noncovalent interactions. The perturbations percolate over neighboring residues and eventually affect the catalytic site and the buried protein core. Validation against a complete experimental site saturation mutagenesis library of BsLipA (3620 variants) reveals that the residues of the perturbation pathways are distinguished sequence positions where substitutions highly likely yield significantly improved residual activity. Our results demonstrate that identifying these perturbation pathways and specific IL ion-residue interactions there effectively predicts focused variant libraries with improved aIL tolerance.

Bioinformatics Analysis of Cellulose Synthase &lt;i&gt;CesA&lt;/i&gt; Gene from &lt;i&gt;Miscanthus lutarioriparius&lt;/i&gt;

Based on 3 generations transcriptome sequencing technology-PacBio SMRT single-molecule real-time sequencing method, supplemented with 2 generation sequencing method, a complete and accurate unigene library was constructed. After comparing with closely related species, the cellulose synthase gene ( CesA ) 4 , 7 , 9 gene sequences of Miscanthus lutarioriparius were spliced and named as MlCesA4 , MlCesA7 and MlCesA9 . Then, Bioinformatics analysis software was used to construct phylogenetic trees of proteins, to predict and analyze the phosphorylation sites of post-translational modifications of amino acids, and to predict and analyze conserved domains of proteins.The analysis results showed that the sequence lengths of MlCesA 4, 7, 9 genes were 2980 bp, 3310 bp, and 3208 bp, respectively, which were closely related to Sorghum bicolor and Zea mays ; cellulose synthase of Miscanthus lutarioriparius (MlCesA) MlCesA4 and MlCesA9 have 43 phosphorylation sites, MlCesA7 has 48 phosphorylation sites; MlCesA4 is an unstable protein with 6 transmembrane domains, 4 domains are outside the membrane and 3 are inside the membrane.; MlCesA7 and MlCesA9 are stable proteins, both of which have 8 transmembrane domains, 5 domains are outside the membrane and 4 are inside the membrane. The three are all hydrophilic proteins, and the secondary structure is dominated by α-helix and random coils.