bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disrupted-in-Schizophrenia-1is required for proper pyramidal cell-interneuron communication and network dynamics in the prefrontal cortex
Authors: Sauer Jonas-Frederic , Bartos Marlene 
Published: December 2021

AbstractWe interrogated prefrontal circuit function in mice lackingDisrupted-in-schizophrenia-1(Disc1-mutant mice), a risk factor for psychiatric disorders. Single-unit recordings in awake mice revealed reduced average firing rates of fast-spiking interneurons (INTs), including optogenetically identified parvalbumin-positive cells, and a lower proportion of INTs phase-coupled to ongoing gamma oscillations. Moreover, we observed decreased spike transmission efficacy at local pyramidal cell (PYR)-INT connectionsin vivo, suggesting a reduced excitatory effect of local glutamatergic inputs as a potential mechanism of lower INT rates. On the network level, impaired INT function resulted in altered activation of PYR assemblies: While assembly activations were observed equally often, the expression strength of individual assembly patterns was significantly higher in Disc1-mutant mice. Our data thus reveal a role of Disc1 in shaping the properties of prefrontal assembly patterns by setting prefrontal INT responsiveness to glutamatergic drive.
Scalable batch-correction approach for integrating large-scale single-cell transcriptomes
Authors: Shen Xilin , Shen Hongru , Wu Dan , Feng Mengyao , Hu Jiani , Liu Jilei , Yang Yichen , Yang Meng , Li Yang , Shi Lei , Chen Kexin , Li Xiangchun 
Published: December 2021

AbstractIntegration of the evolving large-scale single-cell transcriptomes requires scalable batch-correction approaches. Here we propose a simple batch-correction method that is scalable for integrating super large-scale single-cell transcriptomes from diverse sources. The core idea of the method is encoding batch information of each cell as a trainable parameter and added to its expression profile; subsequently, a contrastive learning approach is used to learn feature representation of the additive expression profile. We demonstrate the scalability of the proposed method by integrating 18 million cells obtained from the Human Cell Atlas. Our benchmark comparisons with current state-of-the-art single-cell integration methods demonstrated that our method could achieve comparable data alignment and cluster preservation. Our study would facilitate the integration of super large-scale single-cell transcriptomes. The source code is available athttps://github.com/xilinshen/Fugue.
The Prion Protein Octarepeat Domain Forms Transient β-sheet Structures Upon Residue-Specific Cu(II) and Zn(II) Binding
Authors: Gielnik Maciej , Szymańska Aneta , Dong Xiaolin , Jarvet Jüri , Svedružić Željko M. , Gräslund Astrid , Kozak Maciej , Wärmländer Sebastian K. T. S. 
Published: December 2021

AbstractMisfolding of the cellular prion protein (PrPC) is associated with the development of fatal neurodegenerative diseases called transmissible spongiform encephalopathies (TSEs). Metal ions appear to play a crucial role in the protein misfolding, and metal imbalance may be part of TSE pathologies. PrPCis a combined Cu(II) and Zn(II) metal binding protein, where the main metal binding site is located in the octarepeat (OR) region. Here, we used biophysical methods to characterize Cu(II) and Zn(II) binding to the isolated OR region. Circular dichroism (CD) spectroscopy data suggest that the OR domain binds up to four Cu(II) ions or two Zn(II) ions. Upon metal binding, the OR region seems to adopt a transient antiparallel β-sheet hairpin structure. Fluorescence spectroscopy data indicates that under neutral conditions, the OR region can bind both Cu(II) and Zn(II) ions, whereas under acidic conditions it binds only Cu(II) ions. Molecular dynamics simulations suggest that binding of both metal ions to the OR region results in formation of β-hairpin structures. As formation of β-sheet structures is a first step towards amyloid formation, we propose that high concentrations of either Cu(II) or Zn(II) ions may have a pro-amyloid effect in TSEs.
Third BNT162b2 vaccination neutralization of SARS-CoV-2 Omicron infection
Authors: Nemet Ital , Kliker Limor , Lustig Yaniv , Zuckerman Neta S. , Erster Oran , Cohen Carmit , Kreiss Yitshak , Alroy-Preis Sharon , Regev-Yochay Gili , Mendelson Ella , Mandelboim Michal 
Published: December 2021

AbstractUsing isolates of SARS-CoV-2 WT, Beta, Delta and most importantly Omicron we studied the capability of the BNT162b2 vaccine given in two or three doses to neutralize major SARS-CoV-2 variants of concern (VOC).We demonstrate low neutralization efficiency against delta and wild-type for vaccines with more than 5 months following the second BNT162b2 dose, with no neutralization efficiency against Omicron. We demonstrate the importance of a third dose, by showing a 100-fold increase in neutralization efficiency of Omicron following a third dose, with a 4-fold reduced neutralization compared to that against the Delta VOC. The durability of the effect of the third dose is yet to be determined.
Metabolitin-based molecular drug delivery by targeting GPR158 in glioblastoma
Authors: Zhao Huashan , Zhu Wen , Li Jingwei , Lin Jinju , Lei Xiaohua , Zhang Pengfei , Zhang Jian V. 
Published: December 2021

AbstractGlioblastoma multiforme (GBM) is a lethal form of intracranial tumor. One of the obstacles to treat GBM is the blood-brain barrier which limit the transportation of drugs into the tumor site. Here, based on our previous study on metabolitin (MTL) and osteocalcin, we generated a molecular drug delivery system that consisted of metabolitin and small molecules such as fluorescent dye or peptide drugs for diagnosis and treatment. And we designed a GBM diagnostic probe (MTL-ICG) and therapeutic peptide drug (MTL-NBD) that can cross the blood-brain barrier (BBB). In a NIR animal live imaging system, we found MTL-ICG can penetrate cross BBB and label the GBM site. The in vitro experiment showed that MTL-NBD had inhibitory effect on GBM cell line (U87-MG). Besides, after orthotopic transplantation of GBM into mouse cortex, treatment of MTL-NBD intravenously showed inhibition trend, which were similar with the effect of NBD, a known anti-tumor polypeptide drug. In addition, we found the GPR158, the receptor of osteocalcin, was also high expressed in grafting site. Taken together, these findings suggest that MTL is a promising cell penetrating peptide targeting GPR158 in GBM, which provide a novel delivery tool for GBM.
Production and secretion of functional full-length SARS-CoV-2 spike protein in Chlamydomonas reinhardtii
Authors: Kiefer Anna , Niemeyer Justus , Probst Anna , Erkel Gerhard , Schroda Michael 
Published: December 2021

AbstractThe spike protein is the major protein on the surface of coronaviruses. It is therefore the prominent target of neutralizing antibodies and consequently the antigen of all currently admitted vaccines against SARS-CoV-2. Since it is a 1273-amino acids glycoprotein with 22 N-linked glycans, the production of functional, full-length spike protein was limited to mammalian and insect cells, requiring complex culture media. Here we report the production of full-length SARS-CoV-2 spike protein – lacking the C-terminal membrane anchor – as a secreted protein in the prefusion-stabilized conformation in the unicellular green alga Chlamydomonas reinhardtii. We show that the spike protein is efficiently cleaved at the furin cleavage site during synthesis in the alga and that cleavage is abolished upon mutation of the multi-basic cleavage site. We could enrich the spike protein from culture medium by ammonium sulfate precipitation and demonstrate its functionality based on its interaction with recombinant ACE2 and ACE2 expressed on human 293T cells. Chlamydomonas reinhardtii is a GRAS organism that can be cultivated at low cost in simple media at a large scale, making it an attractive production platform for recombinant spike protein and other biopharmaceuticals in low-income countries.
Systematic discovery of receptor-ligand biology by engineered cell entry and single-cell genomics
Authors: Yu Bingfei , Shi Quanming , Belk Julia A. , Yost Kathryn E. , Parker Kevin R. , Huang Huang , Lingwood Daniel , Davis Mark M. , Satpathy Ansuman T. , Chang Howard Y. 
Published: December 2021

ABSTRACTCells communicate with each other via receptor-ligand interactions on the cell surface. Here we describe a technology for lentiviral-mediated cell entry byengineeredreceptor-ligand interaction (ENTER) to decode receptor specificity. Engineered lentiviral particles displaying specific ligands deliver fluorescent proteins into target cells upon cognate receptor-ligand interaction, without genome integration or transgene transcription. We optimize ENTER to decode interactions between T cell receptor (TCR)-MHC peptides, antibody-antigen, and other receptor-ligand pairs. We develop an effective presentation strategy to capture interactions between B cell receptor (BCR) and intracellular antigen epitopes. Single-cell readout of ENTER by RNA sequencing (ENTER-seq) enables multiplexed enumeration of TCR-antigen specificities, clonality, cell type, and cell states of individual T cells. ENTER-seq of patient blood samples after CMV infection reveals the viral epitopes that drive human effector memory T cell differentiation and inter-clonal phenotypic diversity that targets the same epitope. ENTER enables systematic discovery of receptor specificity, linkage to cell fates, and cell-specific delivery of gene or protein payloads.HIGHLIGHTSENTER displays ligands, deliver cargos, and records receptor specificity.ENTER deorphanizes antigen recognition of TCR and BCR.ENTER-seq maps TCR specificity, clonality and cell state in single cells.ENTER-seq of patient sample decodes antiviral T cell memory.
Fast, live-cell imaging of 15 intracellular compartments by deep learning segmentation of super-resolution data
Authors: Zhanghao Karl , Li Meiqi , Chen Xingye , Liu Wenhui , Wang Yiming , Wu Zihan , Shan Chunyan , Wu Jiamin , Zhang Yan , Xi Peng , Jin Dayong 
Published: December 2021

AbstractThe number of colors that can be used in fluorescence microscopy to image the live-cell anatomy and organelles’ interactions is far less than the number of intracellular organelles and compartments. Here, we report that deep convolutional neuronal networks can predict 15 subcellular structures from super-resolution spinning-disk microscopy images using only one dye, one laser excitation, and two detection channels. Comparing to the colocalization images, this method achieves pixel accuracies of over 91.7%, which not only bypasses the fundamental limitation of multi-color imaging but also accelerates the imaging speed by more than one order of magnitude.
Market orientation, performance and the mediating role of innovation in Indonesian SMEs
Authors: D'souza Clare , Nanere Marthin , Marimuthu Malliga , Arwani Mokhamad , Nguyen Ninh 
Published: December 2021

PurposeDespite the theoretical advancements of market orientation and firm performance, there is a paucity of research regarding SMEs in Indonesia. Customer and competitor orientation were examined as two distinct constructs as per the literature, as it has been questioned for its robustness. They have been used synonymously, even though customer orientation is operationalised as a component of a market orientation construct. There is support for the argument from a theoretical point of view to keep customer orientation and competitor orientation separate. The objective of this research was to empirically test market orientation concepts on firm performance and assessing customer and competitor orientation separately. Furthermore, it also tests whether innovation plays a mediating role.Design/methodology/approachA sample of 309 small and medium-sized firms was found eligible for this study. Structural Equation Modelling was used to analyze the data. A multi-industry sample of firms was used to strengthen the generalisability of the results. The sample was acquired from two databases of SMEs directory in Kudus and Pati, East Java Indonesia, participants were randomly selected.FindingsThe findings show that innovation mediates the relationship between competitor orientation and firm performance, while competitor orientation had no significant relationship with firm performance. Customer orientation was found to positively influence firm performance.Originality/valueThe role of innovation as a mediator within SMEs in a developing country opens up avenues for further research among other developing countries. By examining both the concepts of customer and competitor orientation separately and establishing relationships, we validate support for this argument both from a methodological and theoretical point of view.
Drought-tolerant Bambara groundnuts as future food: a comprehensive review of its properties and applications in food
Authors: Pui Liew-Phing , Tan Wen-Chian , Kong Ianne , Tan Choon-Hui 
Published: December 2021

PurposeThis review provides an overview of the applications of Bambara groundnuts in various food products. The genetic diversity, physical properties and chemical compositions of the crop are also elucidated.Design/methodology/approachThis paper critically reviewed the physicochemical properties and applications of Bambara groundnuts from recent literature.FindingsBambara groundnut (Vigna subterranea) is a drought-tolerant crop from West Africa that contains not only carbohydrates and fats but is also high in protein. The cultivars of Bambara groundnut can be distinguished by the colours of seeds, which range from red, blue-eye, brown and black-eye. Bambara groundnuts contain carbohydrate (57–67%), protein (15–25%), fat (4–8%), fibre (1.4–1.5%) and ash (2.9–4%). As a percentage of protein, the essential amino acids, lysine, methionine and cysteine are relatively high in Bambara groundnuts. Meanwhile, linoleic, palmitic and linolenic acids are the fatty acids present in this crop.Practical implicationsSeveral studies have shown that Bambara groundnuts can be used as fat substitutes, emulsifiers, water binders, bulking agents and thickeners due to its water and oil absorption properties, gelling, pasting, emulsifying and foaming abilities. Bambara groundnuts are used in the development of many intermediate or final products like flour blend, cookies, bread and fermented milk. It has a positive impact on the overall proximate, functional, mineral and amino acid profiles of the food products.Originality/valueDespite its high nutrient density, Bambara groundnuts are an underutilised legume due to unavailability and lack of knowledge among consumers on its benefits. There is a need to promote the use of Bambara groundnuts as a future food.
Creating space and time for innovation - a methodology for building adaptation design appraisal using physics-based simulation tools and interactive multi-objective optimization
Authors: Shahi Sheida , Beesley Philip , Haas Carl Thomas 
Published: December 2021

PurposeIt is crucial to consider the multitude of possible building adaptation design strategies for improving the existing conditions of building stock as an alternative to demolition.Design/methodology/approachIntegration of physics-based simulation tools and decision-making tools such as Multi-Attribute Utility (MAU) and Interactive Multi-objective Optimization (IMO) in the design process enable optimized design decision-making for high-performing buildings. A methodology is presented for improving building adaptation design decision making, specifically in the early-stage design feasibility analysis. Ten residential building adaptation strategies are selected and applied to one primary building system for eight performance metrics using physics-based simulation tools. These measures include energy use, thermal comfort, daylighting, natural ventilation, systems performance, life cycle, cost-benefit and constructability. The results are processed using MAU and IMO analysis and are validated through sensitivity analysis by testing one design strategy on three building systems.FindingsQuantifiable comparison of building adaptation strategies based on multiple metrics derived from physics-based simulations can assist in the evaluation of overall environmental performance and economic feasibility for building adaptation projects.Research limitations/implicationsThe current methodology presented is limited to the analysis of one decision-maker at a time. It can be improved to include multiple decision-makers and capture varying perspectives to reflect common practices in the industry.Practical implicationsThe methodology presented supports affordable generation and analysis of a large number of design options for early-stage design optimization.Originality/valueGiven the practical implications, more space and time is created for exploration and innovation, resulting in potential for improved benefits.
Enhancing perceived product value through peripheral product anecdotes
Authors: Wiener Hillary J.D. , Wiener Joshua , Arnold Todd 
Published: December 2021

Purpose
The purpose of this paper is to introduce a new strategic marketing tool: a peripheral product anecdote (PPA), or a brief, interesting story that is loosely connected to a product but not connected to its history, quality or usage. A PPA is contrasted with similar tools, such as product/brand heritage claims. This study investigates when PPAs are most effective at increasing willingness to pay.

Design/methodology/approach
Five experiments examine the effect of different PPAs on willingness to pay. This study examines product-use situation as a moderator (Studies 3 and 4) and conversational value as a mediator (Studies 2 and 4).

Findings
Customers will pay a premium for products with PPAs, but only when they intend to use the products in social situations where they could share the anecdote with others. Mediation analyses reveal these anecdotes are valuable because they provide purchasers with a conversation topic (a source of social currency).

Practical implications
In contrast to brand heritage stories, nearly any firm can associate a PPA with their product. These anecdotes are a low-cost way for firms to increase willingness to pay for products. PPAs are innovative and varied, unlike brand heritage stories which tend to be static.

Originality/value
This paper shows that customers sometimes want packaged goods, such as beer and snacks, to help them have conversations and will pay more for products that do so. It introduces the PPA as one way marketers can help customers achieve this goal of conversation.
An unsupervised one-class-classifier support vector machine to simultaneously monitor location and scale of multivariate quality characteristics
Authors: Maji Arijit , Mukherjee Indrajit 
Published: December 2021

PurposeThe purpose of this study is to propose an effective unsupervised one-class-classifier (OCC) support vector machine (SVM)-based single multivariate control chart (OCC-SVM) to simultaneously monitor “location” and “scale” shifts of a manufacturing process.Design/methodology/approachThe step-by-step approach to developing, implementing and fine-tuning the intrinsic parameters of the OCC-SVM chart is demonstrated based on simulation and two real-life case examples.FindingsA comparative study, considering varied known and unknown response distributions, indicates that the OCC-SVM is highly effective in detecting process shifts of samples with individual observations. OCC-SVM chart also shows promising results for samples with a rational subgroup of observations. In addition, the results also indicate that the performance of OCC-SVM is unaffected by the small reference sample size.Research limitations/implicationsThe sample responses are considered identically distributed with no significant multivariate autocorrelation between sample observations.Practical implicationsThe proposed easy-to-implement chart shows satisfactory performance to detect an out-of-control signal with known or unknown response distributions.Originality/valueVarious multivariate (e.g. parametric or nonparametric) control chart(s) are recommended to monitor the mean (e.g. location) and variance (e.g. scale) of multiple correlated responses in a manufacturing process. However, real-life implementation of a parametric control chart may be complex due to its restrictive response distribution assumptions. There is no evidence of work in the open literature that demonstrates the suitability of an unsupervised OCC-SVM chart to simultaneously monitor “location” and “scale” shifts of multivariate responses. Thus, a new efficient OCC-SVM single chart approach is proposed to address this gap to monitor a multivariate manufacturing process with unknown response distributions.
An empirical investigation of the professional identification of sales managers and their ethical intentions
Authors: Vocino Andrea , McClaren Nicholas 
Published: December 2021

Purpose
The purpose of this study is to show how senior management can create work environments conducive to ethical behavior in organizations through the use of sales managers’ professionalism and professional identification. The study also aims to demonstrate the influence of professional identification in occupations other than those requiring certification.

Design/methodology/approach
This study conceptualizes and tests a model using data collected from a survey panel of 350 sales managers. To test the hypotheses, this study makes use of covariance structured analysis.

Findings
The results demonstrate the importance of developing sales managers’ professionalism as an antecedent to professional identification. The findings also show professional identification positively affects professional ethical values, work-related norms and occupational commitment. This study finds that work-related norms moderate the relationship between professional ethical values and ethical intentions and directly and positively influence ethical intentions.

Research limitations/implications
This study used a panel sampling technique and these findings cannot be generalized to other populations. This study recommends that this study is replicated not only with sales managers but also with other categories of marketers. This study also highlights that more work using methods such as longitudinal panel data and experimentation is required to validate the current findings.

Practical implications
The findings are of particular interest to senior managers and managers of professional associations, as well as other sales practitioners. Because ethical intentions are affected by work-related norms and from an interaction between work-related norms and professional ethical values, senior managers need to ensure both the work activities in which their staff are involved and the professional ethical values of their employees contribute to appropriate ethical intentions.

Originality/value
This study introduces professional identification into the sales ethics literature and theorize relationships among the professionalism of sales managers and their professional identification, work-related norms, professional ethical values, occupational commitment and ethical intentions. This study empirically measures the professionalism of sales managers.