bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dichotomous Feedback: A Signal Sequestration-based Feedback Mechanism for Biocontroller Design
Authors: Sootla Aivar , Delalez Nicolas , Alexis Emmanouil , Norman Arthur , Steel Harrison , Wadhams George H. , Papachristodoulou Antonis 
Published: December 2021

AbstractWe introduce a new design framework for implementing negative feedback regulation in Synthetic Biology, which we term ‘dichotomous feedback’. Our approach is different from current methods, in that it sequesters existing fluxes in the process to be controlled, and in this way takes advantage of the process’s architecture to design the control law. This signal sequestration mechanism appears in many natural biological systems and can potentially be easier to realise than ‘molecular sequestration’ and other comparison motifs that are nowadays common in biomolecular feedback control design. The loop is closed by linking the strength of signal sequestration to the process output. Our feedback regulation mechanism is motivated by two-component signalling systems, where we introduce a second response regulator competing with the natural response regulator thus sequestering kinase activity. Here, dichotomous feedback is established by increasing the concentration of the second response regulator as the level of the output of the natural process increases. Extensive analysis demonstrates how this type of feedback shapes the signal response, attenuates intrinsic noise while increasing robustness and reducing crosstalk.
Frontal cortical regulation of neurogenesis and cellular proliferation in the ventral subventricular zone
Authors: Naffaa Moawiah M , Khan Rehan R , Kuo Chay T. , Yin Henry H. 
Published: December 2021

SummaryNeurogenesis and differentiation of the neural stem cells (NSCs) in the subventricular zone (SVZ) are controlled by cell-intrinsic molecular pathways that interact with extrinsic signaling cues. Here we identified a novel circuit that regulates neurogenesis and cellular proliferation in the lateral ventricle SVZ (LV-SVZ). Our results demonstrate direct glutamatergic inputs from the frontal cortex as well as local inhibitory interneurons, control the activity of distinctive cholinergic neurons in the subependymal zone (subep-ChAT+). In vivo optogenetic stimulation and inhibition in this circuit were sufficient to control local SVZ neurogenesis, LV NSCs proliferation, and SVZ cellular divisions in ventral SVZ. These findings shed light on local and distal neural circuit activity-dependent regulation of postnatal and adult SVZ neurogenesis and LV-SVZ cellular proliferation.
Booster vaccines protect hamsters with waning immunity from Delta VOC infection, disease, and transmission
Authors: Potts Kyle G. , Noyce Ryan S. , Gafuik Chris , John Cini M. , Todesco Hayley M. , De Heuvel Elaine , Favis Nicole , Kelly Margaret M. , Evans David H. , Mahoney Douglas J. 
Published: December 2021

AbstractWaning immunity to COVID-19 vaccination is associated with increased risk of breakthrough infection, especially with highly transmissible variants of concern (VOC). Booster vaccination generates rapid immune recall in humans, which real-world observational studies suggest protects against VOC infection and associated disease, and modeling studies suggest could mitigate community spread. We directly tested the impact of booster vaccination on protection against Delta VOC infection, disease, and transmission to naïve cohorts in golden Syrian hamsters. Animals with waning immunity to bnt162b2 generated rapid immune recall and strong protection against upper- and lower-respiratory tract infection when boosted with bnt126b2, mRNA-1273 or AZD1222. Boosting with either mRNA vaccine generated moderate protection against lung inflammation and virus transmission to unvaccinated animals. Our data support booster vaccination as a tool to address emerging VOC in the COVID-19 pandemic.One-Sentence SummaryA booster vaccine delivered 9 months after primary bnt162b2 vaccination protects hamsters from Delta VOC infection, disease, and transmission.
The origin of mouse extraembryonic endoderm stem cell lines
Authors: Lin Jiangwei 
Published: December 2021

ABSTRACTMouse extraembryonic endoderm stem (XEN) cell lines can be derived from preimplantation embryos (pre-XEN) and postimplantation embryos (post-XEN). XEN cells share a gene expression profile and cell lineage potential with primitive endoderm (PrE) blastocysts. However, the cellular origin of XEN cells in embryos remains unclear. Here, we report that post-XEN cell lines are derived both from the extraembryonic endoderm and epiblasts of postimplantation embryos and that pre-XEN cell lines are derived both from PrE and epiblasts of blastocysts. Our strategy consisted of deriving post-XEN cells from clumps of epiblasts, parietal endoderm (PE) and visceral endoderm (VE) and deriving pre-XEN cell lines from single PrE and single epiblasts of blastocysts. Thus, XEN cell lines in the mouse embryo originate not only from PrE and PrE-derived lineages but also from epiblast and epiblast-derived lineages of blastocysts and postimplantation embryos.
Identification of Cell-Type-Specific Spatially Variable Genes Accounting for Excess Zeros
Authors: Yu Jinge , Luo Xiangyu 
Published: December 2021

AbstractSpatial transcriptomic techniques can profile gene expressions while retaining the spatial information, thus offering unprecedented opportunities to explore the relationship between gene expression and spatial locations. The spatial relationship may vary across cell types, but there is a lack of statistical methods to identify cell-type-specific spatially variable (SV) genes by simultaneously modeling excess zeros and cell-type proportions. We develop a statistical approach CTSV to detect cell-type-specific SV genes. CTSV directly models spatial raw count data and considers zero-inflation as well as overdispersion using a zero-inflated negative binomial distribution. It then incorporates cell-type proportions and spatial effect functions in the zero-inflated negative binomial regression framework. The Rpackage pscl(Zeileis et al., 2008) is employed to fit the model. For robustness, a Cauchy combination rule is applied to integrate p-values from multiple choices of spatial effect functions. Simulation studies show that CTSV not only outperforms competing methods at the aggregated level but also achieves more power at the cell-type level. By analyzing pancreatic ductal adenocarcinoma spatial transcriptomic data, SV genes identified by CTSV reveal biological insights at the cell-type level. The R package of CTSV is available onhttps://github.com/jingeyu/CTSV.
HSP40 overexpression in pacemaker neurons protects against circadian dysfunction in aDrosophilamodel of Huntington’s Disease
Authors: Prakash Pavitra , Pradhan Arpit Kumar , Sheeba Vasu 
Published: December 2021

AbstractCircadian disturbances are early features of neurodegenerative diseases, including Huntington’s Disease (HD), affecting the quality of life of patients and caregivers. Emerging evidence suggests that circadian decline feeds-forward to neurodegenerative symptoms, exacerbating them, highlighting a need for restoring circadian health. Therefore, we asked whether any of the known neurotoxic modifiers can suppress circadian dysfunction. We performed a screen of neurotoxicity-modifier genes to suppress circadian behavioural arrhythmicity in aDrosophilacircadian HD model. Notably, the molecular chaperones HSP40 and HSP70 (HeatShockProtein) emerged as significant suppressors in the circadian context, with HSP40 being the more potent mitigator of HD-induced deficits. Upon HSP40 overexpression in theDrosophilacircadian ventrolateral neurons (LNv), the behavioural rhythm rescue was associated with neuronal rescue of loss in circadian proteins from small LNv soma. Specifically, there was a restoration of the molecular clock protein Period and its oscillations in young flies and a long-lasting rescue of the output neuropeptide Pigment Dispersing Factor. Significantly, there was a reduction in the expanded Huntingtin inclusion load, concomitant with the appearance of a spot-like Huntingtin form. Thus, we provide evidence for the first time that implicates the neuroprotective chaperone HSP40 incircadian rehabilitation. Given the importance of proteostasis and circadian health in neurodegenerative diseases, the involvement of molecular chaperones in circadian maintenance has broader therapeutic implications.Summary StatementThis study shows, for the first time, a neuroprotective role of chaperone HSP40 in overcoming circadian dysfunction associated with Huntington’s Disease in aDrosophilamodel
Fast and specific enrichment of cancer-related exosomes by DNA-nanoweight-assisted centrifugation
Authors: Lu Zhangwei , shi Ye , Ma Yuxuan , Jia Bin , Li Xintong , Li Zhe 
Published: December 2021

AbstractExosomes are nanoscale membrane vesicles actively released by cells and play an important role in the diagnosis of cancer-related diseases. However, it is challenging to efficiently enrich exosomes from extracellular fluids. In this work, we used DNA-tetrahedron as a nanoweight during centrifugation to precisely enrich tumor exosomes from a complex biological environment. Two different DNA tetrahedral nanostructures (DTAs), each carrying a specific aptamer for exosome biomarker recognition, were incubated with clinical samples simultaneously. One DTA triggered the cross-linking of multiple target exosomes, and therefore enabled low-speed and fast centrifugation for enrichment. The other DTA further narrowed down the target exosome subtype and initiated a hybridization chain reaction (HCR) for sensitive signal amplification. The method enabled the detection of 180 MCF-7-derived exosomes per microliter and 560 HepG2-derived exosomes per microliter, with 1000-fold higher sensitivity than conventional ELISA. This easy-to-operate method can enrich exosomes with excellent specificity and therefore will be appealing in biomedical research and clinical diagnosis.
Mapping prion pathology in mice using quantitative imaging: an MRI study
Authors: Demetriou Eleni , Tachrount Mohamed , Ellis Matthew , Linehan Jackie , Brandner Sebastian , Collinge John , Mead Simon , Shmueli Karin , Farrow Mark , Golay Xavier 
Published: December 2021

AbstractHuman prion diseases are fatal neurodegenerative disorders which cause cognitive impairment and neurological deficits. Additional measures of tissue status are necessary for improving the sensitivity and specificity of clinical diagnosis as in many cases clinical forms of prion disease are commonly mistaken for other forms of dementia. To that effect, we developed a set of quantitative magnetic resonance-based tools, including magnetic resonance spectroscopy (MRS), magnetization transfer ratio (MTR) and quantitative T1 and T2 imaging to study the course of the disease in an animal model of prion disease. Using in vivo MTR, significant changes were detected in the cortex and thalamus of late-stage prion -infected mice as compared to littermates. In addition, we found a significant increase of MTR in thalamus and cortex of 80 dpi healthy mice when compared with 160 dpi healthy mice suggestive of changes occurring during the development of the brain. Using quantitative T2 mapping, significantly higher values were measured in thalamus of prion mice at all stages of the disease (T2=40ms) while T1 was found to be significantly higher in cortex (T1=1.89s) and hippocampus, albeit only in late-stage prion mice as compared to aged-matched controls (T1=1.67s). Using quantitative MRS significant changes were detected in glutamate (Glu) and myo-inositol (Ins) at all stages of prion disease when compared with the control group. NAA, Cr, Lactate and Lipids were only found to be significantly different at early and late stages of the disease while Taurine (Tau) was only significantly increased in the asymptomatic stage without any significant change at early and late stages of the disease. These changes in MRI and MRS signals, which precede clinical signs of disease, could provide insights into the pathogenesis of this disease and may enable early detection of pathology.
FastCAT accelerates absolute quantification of proteins by using multiple short non-purified chimeric standards
Authors: Rzagalinski Ignacy , Bogdanova Aliona , Raghuraman Bharath Kumar , Geertsma Eric R. , Hersemann Lena , Ziemssen Tjalf , Shevchenko Andrej 
Published: December 2021

ABSTRACTAbsolute (molar) quantification of clinically relevant proteins determines their reference values in liquid and solid biopsies. FastCAT (for Fast-track QconCAT) method employs multiple short (<50 kDa) stable-isotope labeled chimeric proteins (CPs) composed of concatenated quantotypic (Q-) peptides representing the quantified proteins. Each CP also comprises scrambled sequences of reference (R-) peptides that relate its abundance to a single protein standard (BSA). FastCAT not only alleviates the need in purifying CP or using SDS-PAGE, but also improves the accuracy, precision and dynamic range of the absolute quantification by grouping Q-peptides according to the expected abundance of target proteins. We benchmarked FastCAT against the reference method of MS Western and tested it in the direct molar quantification of neurological markers in the human cerebrospinal fluid at the low ng/mL level.
Affordable housing in urban India: a review of critical success factors (CSFs) addressing housing adequacy with affordability for the urban poor
Authors: Agarwal Shagun , Singh Tribhuvan Pratap , Bajaj Deepak , Pant Vimal 
Published: December 2021

Purpose
This paper aims to focus on the housing situation in Indian cities and the various stakeholders involved in the housing sector. This study addresses the conflict in expectations of the supply and demand side of the housing and establishes the factors crucial to making housing successful for all the stakeholders, essential for sustainable urban development.

Design/methodology/approach
This paper is developed using the content analysis of preceding independent reviews on housing sustainability by authors across the globe, a review of the current housing situation in Indian cities and a Pilot study of the desired qualitative aspects of housing by the consumer group.

Findings
This paper identifies the challenges and constraints of the various stakeholders involved in the housing sector. A comprehensive list of all the parameters, both qualitative and quantitative, essential for successful housing implementation, focused on the preferences of the demand side, also referred to as the “Critical Success Factors (CSFs)” is generated. The results advocate a strict consideration and integration of these CSFs with the housing policies for all future housing projects.

Research limitations/implications
Most of the studies conducted in the past have reviewed the housing situation in India from the perspective of the government authorities and the initiatives undertaken by them to improve the housing crisis. However, a gap exists in achieving a balanced understanding of the supply-side constraints, with the demand-side expectations from the housing. Focusing only on the supply without adequately understanding the consumption can only lead to further chaos in the already turbulent housing situation.

Originality/value
To the best of author’s knowledge, this is among the first attempts to address the housing scenario in urban centers of India, simultaneously from the perspective of both the demand side and the supply side of the housing, giving additional impetus to the expectations of the demand side which are often ignored. This study becomes more relevant in the ongoing pandemic situation to be able to provide appropriate and acceptable housing solutions to all.
Tertiary wavelet model based automatic epilepsy classification system
Authors: Jaglan Satyender , Dhull Sanjeev Kumar , Singh Krishna Kant 
Published: December 2021

PurposeThis work proposes a tertiary wavelet model based automatic epilepsy classification system using electroencephalogram (EEG) signals.Design/methodology/approachIn this paper, a three-stage system has been proposed for automated classification of epilepsy signals. In the first stage, a tertiary wavelet model uses the orthonormal M-band wavelet transform. This model decomposes EEG signals into three bands of different frequencies. In the second stage, the decomposed EEG signals are analyzed to find novel statistical features. The statistical values of the features are demonstrated using multi-parameters graph comparing normal and epileptic signals. In the last stage, the features are inputted to different conventional classifiers that classify pre-ictal, inter-ictal (epileptic with seizure-free interval) and ictal (seizure) EEG segments.FindingsFor the proposed system the performance of five different classifiers, namely, KNN, DT, XGBoost, SVM and RF is evaluated for the University of BONN data set using different performance parameters. It is observed that RF classifier gives the best performance among the above said classifiers, with an average accuracy of 99.47%.Originality/valueEpilepsy is a neurological condition in which two or more spontaneous seizures occur repeatedly. EEG signals are widely used and it is an important method for detecting epilepsy. EEG signals contain information about the brain's electrical activity. Clinicians manually examine the EEG waveforms to detect epileptic anomalies, which is a time-consuming and error-prone process. An automated epilepsy classification system is proposed in this paper based on combination of signal processing (tertiary wavelet model) and novel features-based classification using the EEG signals.
Contextual factors moderating the impact of strategic management accounting on competitive advantage
Authors: Oyewo Babajide 
Published: December 2021

PurposeThis study investigates the influence of six interrelated contextual factors, namely organisational structure, quality of information technology, business strategy in terms of deliberate strategy-formulation, market orientation, market competition and perceived environmental uncertainty (PEU), on the usage intensity of innovative management accounting techniques commonly referred to as strategic management accounting (SMA); the impact of SMA usage on competitive advantage; and the moderating influence of the contextual factors on the relationship between SMA usage and competitive advantage.Design/methodology/approachSurvey data were obtained through a structured questionnaire from publicly listed manufacturing companies on the main board of the Nigerian Stock Exchange (NSE). Ordinary least squares (OLS) regression and moderated regression were used to analyse data. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used to examine the validity and reliability of variables as first and second order of analysis. Structural equation modelling (SEM) (maximum likelihood estimation method) was applied to assess the robustness of result.FindingsMarket orientation and deliberate strategy-formulation emerged as significant determinants of SMA usage intensity. Although there is a significant relationship between SMA usage and competitive advantage, the strength of the relationship is moderate. Organisational structure, deliberate strategy-formulation and PEU significantly moderate the relationship between SMA usage and competitive advantage.Research limitations/implicationsThe emergence of deliberate strategy-formulation, as both a significant predictor of SMA usage intensity and as the strongest moderator of the relationship between SMA usage and competitive advantage, establish that it is organisations that take a proactive approach to strategy issues that may derive the most benefit from SMA utilisation.Practical implicationsThe result from this study brings to fore the need to involve management accountants in strategy-formulation and implementation in order to leverage their competence in deploying SMA techniques to enhance organisational competitiveness.Originality/valueThe current study is the first, to the researcher's knowledge, to specifically examine interrelated contextual factors distinctively affecting SMA usage and organisational competitiveness in a developing country. Whilst these six factors have been stressed as important determinants of the adoption of innovative management accounting techniques, the study provides empirical evidence on the extent to which they exert on SMA. The study presents empirical evidence on the relevance of market orientation—a construct which has surprisingly received little research attention in management accounting literature—as a variable which could affect the adoption of management accounting innovation.
Everyday genocide: femicide, transicide and the responsibility to protect
Authors: Standish Katerina 
Published: December 2021

Purpose
The purpose of this paper is to establish a conceptual connection between gender-based violence (GBV) and genocide. Victims of gendercide, such as femicide and transicide, should be eligible for protections assigned to victims of genocide, including the Responsibility to Protect (R2P).

Design/methodology/approach
This study examines genocide, gendercide, femicide, transicide and the R2P doctrine to formulate a platform of engagement from which to argue the alignment and congruence of genocide with gendercide. Using a content analysis of the United Nations High Commission for Refugees definition of GBV, and Article II of the Genocide Convention (GC) five “directive” facets are examined, namely, identity, physical violence, psychological violence, oppressive violence and repressive violence.

Findings
Expressions of physical violence, psychological violence, oppressive violence and repressive violence reflected similarity, whereas the GCs omit sex and gender as facets of identity group inclusion. The only variation is the encapsulation of identity factors included in the acts of harm.

Practical implications
The elevation of gendercide to the status of genocide would permit us the leverage to make it not only illegal to permit gendercide – internationally or in-country – but make it illegal not to intervene, too.

Social implications
Deliberate harm based on sex and gender are crimes against people because of their real or perceived group membership, and as such, should be included in genocide theory and prevention.

Originality/value
This study explores a new conceptual basis for addressing gendercidal violence nationally to include sex and gender victim groups typically excluded from formal parameters of inclusion and address due to limitations in Article II. The analysis of genocide alongside GBV may inform scholars and activists in the aim to end gendered violence.