bluuebunny/crossref_metadata_2025 huggingface dataset:
Mucilaginibacter glaciei sp. nov. and Mucilaginibacter pankratovii sp. nov., isolated from a glacier on the Tibetan Plateau
Authors: Yang Lei-Lei , Pang Yu , Liu Hong-Can , Xin Yu-Hua , Liu Qing
Published: December 2020

Two Gram-stain-negative, aerobic, rod-shaped, non-motile, bacterial strains, designated as ZB1P21T and ZT4R22T, were isolated from ice and cryoconite samples collected from Zepu glacier on the Tibetan Plateau, PR China. The phylogenetic analysis of 16S rRNA gene showed that the two strains belong to the genus

Mucilaginibacter

. Strain ZB1P21T showed the highest similarity to

Mucilaginibacter rigui

WPCB133T (97.35 %), while strain ZT4R22T showed the highest similarity to

Mucilaginibacter gilvus

F01003T (99.11 %). The average nucleotide identity values between the two novel strains and their closest relatives were 79.42 and 85.72 % respectively. The two novel strains contained MK-7 as the major menaquinone, and summed feature 3 (comprising C16 : 1
 ω7c and/or C16 : 1
 ω6c), iso-C15:0, iso-C17 : 03-OH and C16 : 1
 ω5c as the major fatty acids. The major polar lipid of the two novel strains were phosphatidylethanolamine. Based on these data, we propose two novel species, Mucilaginibacter glaciei sp. nov. (ZB1P21T=CGMCC 1.23981T=NBRC 113932T) and Mucilaginibacter pankratovii sp. nov. (ZT4R22T=CGMCC 1.23487T=NBRC 113931T).
BiTSC2: Bayesian inference of Tumor clonal Tree by joint analysis of Single-Cell SNV and CNA data
Authors: Chen Ziwei , Gong Fuzhou , Wan Lin , Ma Liang
Published: December 2020

The rapid development of single-cell DNA sequencing (scDNA-seq) technology has greatly enhanced the resolution of tumor cell profiling, providing an unprecedented perspective in characterizing intra-tumoral heterogeneity and understanding tumor progression and metastasis. However, prominent algorithms for constructing tumor phylogeny based on scDNA-seq data usually only take single nucleotide variations (SNVs) as markers, failing to consider the effect caused by copy number alterations (CNAs). Here, we proposeBiTSC2,Bayesianinference ofTumor clonalTree by joint analysis ofSingle-CellSNV andCNA data.BiTSC2takes raw reads from scDNA-seq as input, accounts for sequencing errors, models dropout rate and assigns single cells into subclones. By applying Markov Chain Monte Carlo (MCMC) sampling,BiTSC2can simultaneously estimate the subclonal scCNA and scSNV genotype matrices, sub-clonal assignments and tumor subclonal evolutionary tree. In comparison with existing methods on synthetic and real tumor data,BiTSC2shows high accuracy in genotype recovery and sub-clonal assignment.BiTSC2also performs robustly in dealing with scDNA-seq data with low sequencing depth and variant dropout rate.
A data harmonization pipeline to leverage external controls and boost power in GWAS
Authors: Chen Danfeng , Tashman Katherine , Palmer Duncan S. , Neale Benjamin , Roeder Kathryn , Bloemendal Alex , Churchhouse Claire , Ke Zheng Tracy
Published: December 2020

Abstract

The use of external controls in genome-wide association study (GWAS) can significantly increase the size and diversity of the control sample, enabling high-resolution ancestry matching and enhancing the power to detect association signals. However, the aggregation of controls from multiple sources is challenging due to batch effects, difficulty in identifying genotyping errors, and the use of different genotyping platforms. These obstacles have impeded the use of external controls in GWAS and can lead to spurious results if not carefully addressed. We propose a unified data harmonization pipeline that includes an iterative approach to quality control (QC) and imputation, implemented before and after merging cohorts and arrays. We apply this harmonization pipeline to aggregate 27,517 European control samples from 16 collections within dbGaP. We leverage these harmonized controls to conduct a GWAS of Crohn’s disease. We demonstrate a boost in power over using the cohort samples alone, and that our procedure results in summary statistics free of any significant batch effects. This harmonization pipeline for aggregating genotype data from multiple sources can also serve other applications where individual level genotypes, rather than summary statistics, are required.
Accuracy of automated computer aided-risk scoring systems to estimate the risk of COVID-19 and in-hospital mortality: a retrospective cohort study
Authors: Faisal Muhammad , Mohammed Mohammed A , Richardson Donald , Fiori Massimo , Beatson Kevin
Published: December 2020

Objectives

Although a set of computer-aided risk scoring systems (CARSS), that use the National Early Warning Score and routine blood tests results, have been validated for predicting in-hospital mortality and sepsis in unplanned admission to hospital, little is known about their performance for COVID-19 patients. We compare the performance of CARSS in unplanned admissions with COVID-19 during the first phase of the pandemic.

Design

a retrospective cross-sectional study

Setting

Two acute hospitals (Scarborough and York) are combined into a single dataset and analysed collectively.

Participants

Adult (>=18 years) non-elective admissions discharged between 11-March-2020 to 13-June-2020 with an index NEWS electronically recorded within ±24 hours. We assessed the performance of all four risk score (for sepsis: CARS_N, CARS_NB; for mortality: CARM_N, CARM_NB) according to discrimination (c-statistic) and calibration (graphically) in predicting the risk of COVID-19 and in-hospital mortality.

Results

The risk of in-hospital mortality following emergency medical admission was 8.4% (500/6444) and 9.6% (620/6444) had a diagnosis of COVID-19. For predicting COVID-19 admissions, the CARS_N model had the highest discrimination 0.73 (0.71 to 0.75) and calibration slope 0.81 (0.72 to 0.89). For predicting in-hospital mortality, the CARM_NB model had the highest discrimination 0.84 (0.82 to 0.75) and calibration slope 0.89 (0.81 to 0.98).

Conclusions

Two of the computer-aided risk scores (CARS_N and CARM_NB) are reasonably accurate for predicting the risk of COVID-19 and in-hospital mortality, respectively. They may be clinically useful as an early warning system at the time of admission especially to triage large numbers of unplanned hospital admissions because they are automated and require no additional data collection.

Article Summary

In this study, we found that two of the automated computer-aided risk scores are reasonably accurate for predicting the risk of COVID-19 and in-hospital mortality, respectively.

They may be clinically useful as an early warning system at the time of admission especially to triage large numbers of unplanned hospital admissions because they are automated and require no additional data collection.

Although we focused on in-hospital mortality (because we aimed to aid clinical decision making in the hospital), the impact of this selection bias needs to be assessed by capturing out-of-hospital mortality by linking death certification data and hospital data.

We identified COVID-19 based on ICD-10 code ‘U071’ which was determined by COVID-19 swab test results (hospital or community) and clinical judgment and so our findings are constrained by the accuracy of these methods
Biliverdin reductase bridges focal adhesion kinase to Src to modulate synaptic signaling
Authors: Vasavda Chirag , Semenza Evan R. , Liew Jason , Kothari Ruchita , Dhindsa Ryan S. , Shanmukha Shruthi , Ricco Cristina , Tokhunts Robert , Snowman Adele M. , Albacarys Lauren , Paul Bindu D. , Snyder Solomon H.
Published: December 2020

Synapses are complex bridges that connect discrete neurons into vast networks that send, receive, and encode diverse forms of information. However, they must remain dynamic in order to adapt to changing inputs. Here, we report that the enzyme biliverdin reductase (BVR) physically links together key molecules in focal adhesion signaling at the synapse. In challenging mice with a battery of neurocognitive tasks, we first discover that BVR null (BVR-/-) mice exhibit profound deficits in learning and memory. We uncover that these deficits may be explained by a loss of focal adhesion signaling that is both transcriptionally and biochemically disrupted in BVR-/-hippocampi. We learn that BVR mediates focal adhesion signaling by physically bridging the initiatory kinases FAK/Pyk2 to the effector kinase Src. Activated Src normally promotes synaptic plasticity by phosphorylating the N-methyl-D-aspartate (NMDA) receptor, but FAK/Pyk2 are unable to bind and stimulate Src without BVR. Src itself is a molecular hub upon which many signaling pathways converge in order to stimulate NMDA neurotransmission, positioning BVR at a prominent intersection of synaptic signaling.
Convolutional neural networks for automated CMR image segmentation in rats with myocardial infarcts
Authors: Gondova Andrea , Zurek Magdalena , Karlsson Johan , Hultin Leif , Noeske Tobias , Watson Edmund
Published: December 2020

In translational cardiovascular research, delineation of left ventricle (LV) in magnetic resonance images is a crucial step in assessing heart’s function. Performed manually, this task is time-consuming and prone to inter- and intra-reader variability. Here we report first AI-based tool for segmentation of rat cardiovascular MRI. The method is an ensemble of fully convolutional networks and can quantify clinically relevant measures: end-diastolic volume (EDV), end-systolic volume (ESV), and ejection fraction (EF) automatically.

Overall, our method reaches Dice score of 0.93 on the independent test set. The mean absolute difference of segmented volumes between automated and manual segmentation is 22.5μL for EDV, 13.6μL for ESV, and for EF 2.9%. Our work demonstrates the value of AI in development of tools that will significantly reduce time spent on repetitive work and result in increased efficiency of reporting data to project teams.
Development of an Antiseizure Drug Screening Platform for Dravet Syndrome at the NINDS contract site for the Epilepsy Therapy Screening Program
Authors: Pernici Chelsea D. , Mensah Jeffrey A. , Dahle Elizabeth J. , Johnson Kristina J. , Handy Laura , Buxton Lauren , Smith Misty D. , West Peter J. , Metcalf Cameron S. , Wilcox Karen S.
Published: December 2020

Objective

Dravet syndrome (DS) is a rare, but catastrophic genetic epilepsy, with 80% of patients with carrying a mutation in the SCN1A gene. Currently, no anti-seizure drug (ASD) exists that adequately controls seizures. Patients with DS often present clinically with a febrile seizure and generalized tonic-clonic seizures that continue throughout life. To facilitate the development of ASDs for DS, the contract site of the NINDS Epilepsy Therapy Screening Program (ETSP) has evaluated a mouse model of DS using the conditional knock-inScn1aA1783V/WTmouse.

Methods

Survival rates and temperature thresholds forScn1aA1783V/WTwere determined. Prototype ASDs were administered via intraperitoneal injections at the time-to-peak effect, which was previously determined, prior to the induction of hyperthermia-induced seizures. Protection was determined if ASDs significantly increased the temperature at whichScn1aA1783V/WTmice seized.

Results

Approximately 50% ofScn1aA1783V/WTsurvive to adulthood and all have hyperthermia-induce seizures. The results suggest that hyperthermia-induced seizures in this model of DS are highly refractory to a battery of ASDs. Exceptions were clobazam, tiagabine, and the combination of clobazam and valproic acid with add-on stiripentol, which elevated seizure thresholds

Significance

Overall, the data demonstrate the proposed model for DS is suitable for screening novel compounds for the ability to block hyperthermia-induced seizures and heterozygous mice can be evaluated repeatedly over the course of several weeks, allowing for higher throughput screening.

Key Points

Scn1aA1783V/WTmice have a 50% survival rate and all have hyperthermia-induced seizures.

Common DS treatments such as CLB and combinatorial therapy of CLB, VPA, and STP increase temperature thresholds inScn1aA1783V/WTmice.

Sodium channel blockers, such as CBZ and LTG, decrease temperature thresholds ofScn1aA1783V/WTmice as predicted.

Scn1aA1783V/WTmice are highly pharmacoresitant to common ASDs

TheScn1aA1783V/WTmay be a useful preclinical drug screening platform for the treatment of DS.
High-speed, multicolor, structured illumination microscopy using a hexagonal single mode fiber array
Authors: Hinsdale Taylor A. , Stallinga Sjoerd , Rieger Bernd
Published: December 2020

Structured Illumination Microscopy (SIM) is a widely used imaging technique that doubles the effective resolution of widefield microscopes. Most current implementations rely on diffractive elements, either gratings or programmable devices, to generate structured light patterns in the sample. These can be limited by spectral efficiency, speed, or both. Here we introduce the concept of fiber SIM which allows for camera frame rate limited pattern generation and manipulation over a broad wavelength range. Illumination patterns are generated by coupling laser beams into radially opposite pairs of fibers in a hexagonal single mode fiber array where the exit beams are relayed to the microscope objective’s back focal plane. The phase stepping and rotation of the illumination patterns are controlled by fast electro-optic devices. We achieved a rate of 111 SIM frames per second and imaged with excitation patterns generated by both 488 nm and 532 nm lasers.
RTN3 inhibits RIGI-I-mediated antiviral responses by impairing TRIM25-mediated K63-linked polyubiquitination
Authors: Yang Ziwei , Wang Jun , He Bailin , Zhang Xiaolin , Li Xiaojuan , Kuang Ersheng
Published: December 2020

Upon viral RNA recognition, the RIG-I signalosome continuously generates IFNs and cytokines, leading to neutrophil recruitment and inflammation. Thus, attenuation of excessive immune and inflammatory responses is crucial to restore immune homeostasis and prevent unwarranted damage, yet few proresolving mediators have been identified. In the present study, we demonstrated that RTN3 is strongly upregulated during RNA viral infection and acts as an inflammation-resolving regulator. Increased RTN3 aggregates on the endoplasmic reticulum and interacts with both TRIM25 and RIG-I, subsequently impairing K63-linked polyubiquitination and resulting in both IRF3 and NF-κB inhibition. Rtn3 overexpression in mice causes an obvious inflammation resolving phenomenon when challenged with VSV, Rtn3-overexpressing mice display significantly decreased neutrophil numbers and inflammatory cell infiltration, which is accompanied by reduced tissue edema in the liver and thinner alveolar interstitium. Taken together, our findings identify RTN3 as a conserved proresolving mediator of immune and inflammatory responses and provide insights into the negative feedback that maintains immune and inflammatory homeostasis.

RTN3 is upregulated upon RNA viral infection due to inflammation and ER stress, in turn suppresses antiviral responses by impairing TRIM25-mediated RIG-I K63-linked polyubiquitination and consequently decreases neutrophil populations and inflammatory infiltration, representing a novel mechanism of negative inflammatory resolution.
Repurposing the Ebola and Marburg Virus Inhibitors Tilorone, Quinacrine and Pyronaridine: In vitro Activity Against SARS-CoV-2 and Potential Mechanisms
Authors: Puhl Ana C. , Fritch Ethan James , Lane Thomas R. , Tse Longping V. , Yount Boyd L. , Sacramento Carol Queiroz , Tavella Tatyana Almeida , Costa Fabio Trindade Maranhão , Weston Stuart , Logue James , Frieman Matthew , Premkumar Lakshmanane , Pearce Kenneth H. , Hurst Brett L. , Andrade Carolina Horta , Levi James A. , Johnson Nicole J. , Kisthardt Samantha C. , Scholle Frank , Souza Thiago Moreno L. , Moorman Nathaniel John , Baric Ralph S. , Madrid Peter , Ekins Sean
Published: December 2020

SARS-CoV-2 is a newly identified virus that has resulted in over 1.3 M deaths globally and over 59 M cases globally to date. Small molecule inhibitors that reverse disease severity have proven difficult to discover. One of the key approaches that has been widely applied in an effort to speed up the translation of drugs is drug repurposing. A few drugs have shownin vitroactivity against Ebola virus and demonstrated activity against SARS-CoV-2in vivo. Most notably the RNA polymerase targeting remdesivir demonstrated activityin vitroand efficacy in the early stage of the disease in humans. Testing other small molecule drugs that are active against Ebola virus would seem a reasonable strategy to evaluate their potential for SARS-CoV-2. We have previously repurposed pyronaridine, tilorone and quinacrine (from malaria, influenza, and antiprotozoal uses, respectively) as inhibitors of Ebola and Marburg virusin vitroin HeLa cells and of mouse adapted Ebola virus in mousein vivo. We have now tested these three drugs in various cell lines (VeroE6, Vero76, Caco-2, Calu-3, A549-ACE2, HUH-7 and monocytes) infected with SARS-CoV-2 as well as other viruses (including MHV and HCoV 229E). The compilation of these results indicated considerable variability in antiviral activity observed across cell lines. We found that tilorone and pyronaridine inhibited the virus replication in A549-ACE2 cells with IC50values of 180 nM and IC50198 nM, respectively. We have also tested them in a pseudovirus assay and used microscale thermophoresis to test the binding of these molecules to the spike protein. They bind to spike RBD protein with Kdvalues of 339 nM and 647 nM, respectively. Human Cmaxfor pyronaridine and quinacrine is greater than the IC50hence justifyingin vivoevaluation. We also provide novel insights into their mechanism which is likely lysosomotropic.
Bivalent chromatin protects reversibly repressed genes from irreversible silencing
Authors: Kumar Dhirendra , Jothi Raja
Published: December 2020

Bivalent chromatin is characterized by the simultaneous presence of H3K4me3 and H3K27me3, histone modifications generally associated with transcriptionally active and repressed chromatin, respectively. Prevalent in embryonic stem cells, bivalency is postulated to poise lineage-controlling developmental genes for rapid activation during embryogenesis while maintaining a transcriptionally repressed state in the absence of activation cues, but its function in development and disease remains a mystery. Here we show that bivalency does not poise genes for rapid activation but protects reversibly repressed genes from irreversible silencing. We find that H3K4me3 at bivalent gene promoters—a product of the underlying DNA sequence—persists in nearly all cell types irrespective of gene expression and confers protection fromde novoDNA methylation. Accordingly, loss of H3K4me3 at bivalent promoters is strongly associated with aberrant hypermethylation and irreversible silencing in adult human cancers. Bivalency may thus represent a distinct regulatory mechanism for maintaining epigenetic plasticity.

HIGHLIGHTS

Bivalent chromatin does not poise genes for rapid activation

H3K4me3 at bivalent promoters is not instructive for transcription activation

H3K4me3 at bivalent promoters protects reversibly repressed genes fromde novoDNA methylation

Loss of H3K4me3/bivalency is associated with aberrant DNA hypermethylation in cancer
A time-course study of actively stained mouse brains: DTI parameter and connectomic stability over one year
Authors: Xiao Jaclyn , Hornburg Kathryn J. , Cofer Gary , Cook James J. , Qi Yi , Johnson G Allan
Published: December 2020

While the application of diffusion tensor imaging (DTI), tractography, and connectomics to fixed ex-vivo tissue is a common practice today, there have been limited studies examining the effects of fixation on brain microstructure over extended periods. This time-course study reports the changes of regional brain volumes and diffusion scalar parameters, such as fractional anisotropy across twelve representative brain regions as measures of brain structural stability. The scalar DTI parameters and regional volumes were highly variable over the first two weeks after fixation. The same parameters were stable over a two to eight-week window after fixation which means confounds from tissue stability over that scanning window are minimal. Quantitative connectomes were analyzed over the same time period with extension out to one year. While there is some change in the scalar metrics at one year after fixation, these changes are sufficiently small, particularly in white matter to support reproducible connectomes over a period ranging from two weeks to one year post fixation. These findings delineate a stable scanning period during which brain volumes, diffusion scalar metrics and connectomes are remarkably stable.
FGF2 disruption enhances thermogenesis in brown and beige fat to protect against obesity and hepatic steatosis
Authors: Li Haifang , Zhang Xinzhi , Huang Cheng , Liu Huan , Liu Shuang , Zhang Qiang , Dong Mei , Hou Mengjie , Liu Yiming , Lin Hai
Published: December 2020

Since brown and beige fat expend energy in the form of heat via non-shivering thermogenesis, identifying key regulators of thermogenic functions represents a major goal for development of potential therapeutic avenues for obesity and associated disorders. Here, we identified fibroblast growth factor 2 (FGF2) as a novel thermogenic regulator. FGF2 gene disruption resulted in increased thermogenic capability in both brown and beige fat, which was supported by increased UCP1 expression, enhanced respiratory exchange ratio, and elevated thermogenic potential under cold challenge or β-adrenergic stimulation. Thus, deletion of FGF2 protected mice from high fat-induced obesity and hepatic steatosis. Mechanistically, FGF2 acts in autocrine/paracrine fashionsin vitro. Exogenous FGF2 supplementation inhibits both PGC-1α and PPARγ expression through ERK phosphorylation, thereby limiting PGC-1α/PPARγ interactions, and leading to suppression of UCP1 expression and thermogenic activity in brown and beige adipocytes. These findings suggest a viable potential strategy for use of FGF2-selective inhibitors in treatment of combating obesity and related disorders.
Effectivein-vitroinactivation of SARS-CoV-2 by commercially available mouthwashes
Authors: Davies Katherine , Buczkowski Hubert , Welch Stephen R , Green Nicole , Mawer Damian , Woodford Neil , Roberts Allen DG , Nixon Peter J , Seymour David W , Killip Marian J
Published: December 2020

Infectious SARS-CoV-2 can be recovered from the oral cavities and saliva of COVID-19 patients with potential implications for disease transmission. Reducing viral load in patient saliva using antiviral mouthwashes may therefore have a role as a control measure in limiting virus spread, particularly in dental settings. Here, the efficacy of SARS-CoV-2 inactivation by seven commercially available mouthwashes with a range of active ingredients were evaluatedin vitro. We demonstrate ≥4.1 to ≥5.5 log10reduction in SARS-CoV-2 titre following a one minute treatment with commercially available mouthwashes containing 0.01-0.02% stabilised hypochlorous acid or 0.58% povidone iodine, and non-specialist mouthwashes with both alcohol-based and alcohol-free formulations designed for home use. In contrast, products containing 1.5% hydrogen peroxide or 0.2% chlorhexidine gluconate were ineffective against SARS-CoV-2 in these tests. This study contributes to the growing body of evidence surrounding virucidal efficacy of mouthwashes/oral rinses against SARS-CoV-2, and has important applications in reducing risk associated with aerosol generating procedures in dentistry and potentially for infection control more widely.
A promiscuous archaeal cardiolipin synthase generating a variety of cardiolipins and phospholipids
Authors: Exterkate Marten , de Kok Niels A. W. , Andringa Ruben L. H. , Wolbert Niels H. J. , Minnaard Adriaan J. , Driessen Arnold J. M.
Published: December 2020

Cardiolipin (DPCL) biosynthesis has barely been explored in Archaeal isoprenoid-based ether lipid membranes. Here, we identified a cardiolipin synthase (MhCls) from the mesophilic anaerobic methanogenMethanospirillum hungatei.The enzyme was overexpressed inEscherichia coli,purified, and subsequently characterized by LC-MS. MhCls utilizes two archaetidylglycerol molecules in a transesterification reaction to synthesize archaeal di-phosphate cardiolipin (aDPCL) and glycerol. The enzyme is invariant to the stereochemistry of the glycerol-backbone and the nature of the lipid tail, as it also accepts phosphatidylglycerol to generate di-phosphate cardiolipin (DPCL). Remarkably, in the presence of archaetidylglycerol and phosphatidylglycerol, MhCls formed an archaeal-bacterial hybrid di-phosphate cardiolipin (hDPCL), that so far has not been observed in nature. Due to the reversibility of the transesterification, cardiolipin can be converted back in presence of glycerol into phosphatidylglycerol. In the presence of other compounds that contain primary hydroxyl groups (e.g. alcohols, water, sugars) various natural and unique artificial phospholipid species could be synthesized, including multiple di-phosphate cardiolipin species. Moreover, MhCls could utilize a glycolipid in the presence of phosphatidylglycerol to form a glycosyl-mono-phosphate cardiolipin, emphasizing the promiscuity of this cardiolipin synthase.
An Expanded Class of Histidine-Accepting Viral tRNA-like Structures
Authors: Langeberg Conner J. , Sherlock Madeline E. , MacFadden Andrea , Kieft Jeffrey S.
Published: December 2020

Structured RNA elements are common in the genomes of RNA viruses, often playing critical roles during viral infection. Some RNA elements use forms of tRNA mimicry, but the diverse ways this mimicry can be achieved are poorly understood. Histidine-accepting tRNA-like structures (TLSHis) are examples found at the 3′ termini of some positive-sense single-stranded RNA (+ssRNA) viruses where they interact with several host proteins, induce histidylation of the RNA genome, and facilitate several processes important for infection, to include replication. As only five TLSHisexamples had been reported, we explored the possible larger phylogenetic distribution and diversity of this TLS class using bioinformatic approaches. We identified many new examples of TLSHis, yielding a rigorous consensus sequence and secondary structure model that we validated by chemical probing of representative TLSHisRNAs. We confirmed new examples as authentic TLSHisby demonstrating their ability to be histidylatedin vitro, then used mutational analyses to verify a tertiary interaction that is likely analogous to the D- and T-loop interaction found in canonical tRNAs. These results expand our understanding of how diverse RNA sequences achieve tRNA-like structures and functions in the context of viral RNA genomes and lay the groundwork for high-resolution structural studies of tRNA mimicry by histidine-accepting TLSs.
Human spinal cord organoids exhibiting neural tube morphogenesis for a quantifiable drug screening system of neural tube defects
Authors: Lee Ju-Hyun , Shin Hyogeun , Shaker Mohammed R. , Kim Hyun Jung , Kim June Hoan , Lee Namwon , Kang Minjin , Cho Subin , Kwak Tae Hwan , Kim Jong Woon , Song Mi-Ryong , Kwon Seung-Hae , Han Dong Wook , Lee Sanghyuk , Choi Se-Young , Rhyu Im Joo , Kim Hyun , Geum Dongho , Cho Il-Joo , Sun Woong
Published: December 2020

The human spinal cord forms well-organized neural circuits for environment sensing and motor behavior. The three-dimensional (3D) induction of the spinal cord-like tissue from human pluripotent stem cells has been reported, but they often do not mimic morphological features of neurulation and their maturity is limited. Here, we report an advanced 3D culture system for the production of human spinal cord-like organoids (hSCOs) suitable for the scale-up and quantitative studies. The hSCOs exhibited many aspects of spinal cord development, including neurulation-like tube-forming morphogenesis, differentiation of the major spinal cord neurons and glial cells, and mature synaptic functional activities. We further demonstrated that hSCOs platform allowed quantitative and systematic high-throughput examination of the potential risk of neural tube defects induced by antiepileptic drugs. Thus, hSCOs can be used for understanding human spinal cord development, disease modeling, and toxicology screening.
Discovery IQ by GE: Launching Super Value PET/CT Scanner
Authors: Jaiswal Anand Kumar , Malodia Suresh
Published: December 2020

It was mid-March 2014, and GE's John F. Welch Technology Centre in Bangalore, India was brimming with activity. GE had developed an advanced, scalable positron emission tomography-computed tomography (PET/CT) scanner as part of its global Healthymagination initiative to provide better healthcare for more people at a lower cost. Munesh Makhija, Managing Director, GE India Technology Centre and Chief Technology Officer (CTO), GE South Asia, was thumbing through a report prepared by the PET/CT product development team and GE's healthcare market research team. In another office, Suresh Kumar R.(Kumar), General Manager of the Essential PET Segment, was putting the finishing touches on a presentation outlining a commercialisation strategy for the new PET/CT product, Discovery IQ (Exhibit 1).

Discovery IQ was a revolutionary product that would be useful for staging, treatment planning and post-treatment planning assessment. Early reviews from nuclear physicians had been positive. However, the product was still too costly for the bottom of the pyramid (BoP) market. Kumar and his team were scheduled to meet with Makhija the following morning to discuss a “go-to-market strategy”. Kumar knew that Makhija would want to talk about their segmentation strategy and the underlying needs of various customer types. He also expected Makhija to focus on return on investment (ROI) projections because diagnostic centres in India first looked at various financial return measures before investing in any new equipment. Kumar wanted to present a commercialisation strategy for Discovery IQ, which required a significant commitment of resources to tackle supply and distribution challenges across tier II and tier III citiesa in India.
Wendt India Limited
Authors: Bathini Dharma Raju , Vohra Neharika , Jaiswal Manoj
Published: December 2020

Consistent growth and profitability had been the bedrock of Wendt India Limited (WIL) over the past ten years, in spite of facing huge financial mismanagement in the initial years and three ownership changes at group level. The strategic intent of WIL, “Wendt India sought to become a significant global player in offering customized functionally superior products/services for grinding and machining hard-to-process material,” kept the leaders of the company focused on exceptional performance. Despite a remarkable track record, WIL posted a lower growth 3.1% (CAGR) during 2007–2010, against an impressive 18% (CAGR) during 2000–2007 (See Exhibit 1). Rajesh Khanna, Chief Executive Officer of WIL, knew that the company's growth was tied to the perceptible slowdown in the economy post 2007. Industry analysts speculated that over the next few years, the abrasive industry itself was expected to grow at 7.2% per annum, mirroring the GDP growth rate. Goaded by the group chairperson's expectation that each business within the Murugappa group had to grow at three times the country's GDP growth rate, and personal belief that slowing down was not an option, Rajesh had set aggressive targets. He knew he would have to provide direction on how to reach the set expectations. He needed a coherent and strategic action plan to meet the aggressive targets.
Sandwichworkz - The Fusion Street Café
Authors: Roy Debjit , Raut Mukund , Agrawal Sanchit , Agrawal Shubham
Published: December 2020

Takshshila, the owner of Sandwichworkz, a trendy restaurant in Ahmedabad, India, is worried about the diminishing profitability of her restaurant. Recent promotional offers have increased the footfall, but not profitability. To address this issue, she knew she had to optimize and redesign their menu. She also realizes that to properly address this issue, they would beed to take into account factors such as popularity of each menu item and their per unit profitability. She contacts Nick, a restaurant consultant who further dwells into calculating the costs involved in making each item, to determine the per unit profitability. He proposed plotting the popularity vs. popularity graph (as per Kasavana Smith model) and making qyadrant specific re-enginering decisions. Post his analysis using this menu re-engineering tool, he calls Takshshila with his recommendations. During the call, they come across a new costing methodology which may affect his recommendations. Which methodology should Nick use? Should Takshshila invest in capturing data for the new methodology?
Nagpur Golden Transport Company: From Data to Insights
Authors: Roy Debjit
Published: December 2020

The case focuses on truck high idle time, truck detention, and enroute challenges faced by Nagpur Golden Transport Company, a trucking company with a fleet size of 150 trucks. Being in a highly competitive market, every single order not fulfilled by the transporter is an opportunity lost. How should NGTC use GPS data, MIS, and other freight transport technological capabilities in reducing truck idling times, and increasing trip revenues?
Zerodha - A Success Story(B)
Authors: Garg Archit , Gupta Aashish , Maheshwari Garima , Sinha Ankur , Sugathan Anish
Published: December 2020

The transparency and consistency of Zerodha provided them mileage and the business model certainly disrupted the Indian brokerage industry. The zero-commission model was successful in attracting consumers and provided tough competition to other brokers. However, competitive advantage coming solely from low pricing may not always be sustainable in the long run. This case explores the sustainability of the business model and looks at alternatives that are important for a long term scale-up of Zerodha.
Adani Power Limited (B): Renegotiating Long-term Electricity Contracts
Authors: Pandey Ajay
Published: December 2020

Adani Power Limited (B) is the second case in a series of cases on the attempts by the firm to wriggle out of the negative consequences of the long-term fixed price power purchase agreements it had entered into. Changes in Indonesian regulations for coal exported from Indonesia created serious financial problems for the firm. This case describes how the firm was able to get relief from the regulator and raises public policy issues including the robustness of guidelines for procurement of power and the regulatory framework.
A human touch and content matter for consumer engagement on social media
Authors: Park Hyojung , Jiang Yangzhi
Published: December 2020

Purpose

The purpose of this study is to examine what individual motives (e.g., self-expression or rewards) and brand communication aspects (such as content) influence consumers' brand engagement behaviors, and how these behaviors are linked to their intentions in favor of a brand.

Design/methodology/approach

The authors conducted an online survey with a quota sample of 629 adults in the United States. Participants were recruited through a Qualtrics online panel.

Findings

Data indicate that the motivations of entertainment and remuneration are positively associated with consuming and contributing to brand content on social media. In addition, the motive of obtaining information prompts people to consume brand content (e.g., reading a brand's posts or watching videos), while the motivation for self-expression leads to contributing activities (e.g., conversing on a brand's account and uploading videos). After controlling for these motivations, brand communication strategy (such as content and tone) appears to influence consumers' brand-related activities on social media, which subsequently results in consumer intentions in favor of the brand.

Originality/value

Consumer engagement in social media has become the primary focus of corporate communication. This work is one of few studies that have explored how consumer motivation and brand communication come together to generate consumer engagement on social media. The overall findings shed light on how corporate communications can generate consumer engagement on social media and how companies reap benefits from it.
Panel data or pseudo panels for longitudinal research? Cross-national comparisons using the example of firms' training spend
Authors: Brookes Michael , Brewster Chris , Gedikli Cigdem , Yilmaz Okan
Published: December 2020

Purpose

The evolution of firm level practices over time has always been a keen area of interest for management scholars. However, in comparison to other social scientists, particularly economists, the relative dearth of firm level panel data sets has restricted the methodological options for exploring inter-temporal changes.

Design/methodology/approach

This paper applies a pseudo panel methodology to investigate the evolution of training spend at the firm level over time.

Findings

The analysis is framed within a varieties of capitalism lens and by adopting a more meaningful approach to examining changes over time it leads us to question some of the “truisms” linked to firms expected behaviours within different national institutional frameworks.

Research limitations/implications

As with any large-scale quantitative analysis, it would always benefits from a larger number of observations and/or a longer time period, in this instance access to annual data rather than 4 or 5 year intervals would have been helpful.

Practical implications

By adopting a different, and more appropriate, approach to analysing existing cross-sectional data over time this empirical research helps to achieve a deeper understanding of the complex issues that influence decision making at the firm level.

Social implications

At the firm level, in line with the practical implications above, this will enable decision makers to achieve a deeper understanding of the evolution of the external context in which they operate and the likely influence of that evolution within their own organisation.

Originality/value

This approach enables a more meaningful exploration of inter-temporal changes in situations where longitudinal data does not exist.
Form tolerance analysis and multi-parametric optimization of meso deep square hole EDMed on Inconel-718 plate using GRA method
Authors: Kumar Sandeep , Dhanabalan S.
Published: December 2020

Purpose

The main objective of this experimental work is to analyze and measure the form tolerances namely flatness and squareness while machining a meso deep hole in EDM on Inconel-718 material plate.

Design/methodology/approach

The experiments were performed on 15 amps rated SPARKONIX-EDM as per DOE (design of experiments). Kerosene was used as a dielectric along with constant pressure of 0.2 kg/cm2 for all trial runs. The currents Ton and Toff were selected as process constraints to conduct experimental trials. The MRR, EWR, machining time and form tolerances were considered as output responses. The experimental outcomes were optimized by hybrid optimization using Taguchi and GRA (grey relational analysis) method.

Findings

The EDM process parameters for Ni-based super alloy namely Inconel-718 had optimized by using GRA method coupled with Taguchi method. The optimum solution has been calculated for MRR, EWR, machining time and form tolerances namely squareness and flatness. The optimized parameters for the output responses in EDM process are Peak current (Ip) 12 Amps, 400 µs Ton (pulse on time) and 10 µs Toff (pulse off time). An attempt had also been made to attain Max. and Min. Evaluation of MRR and form tolerances, respectively. The attained optimum outcomes had also been examined through a real experiment and established to be satisfactory.

Practical implications

This article will facilitate the defense, aerospace and EDM industries to improve their productivity with closer tolerances.

Originality/value

The optimized parameters by multi-parametric optimization showed the considerable improvement in the process and will facilitate the defense, aerospace and EDM industries to improve their productivity with closer tolerances.
Development of a 3D technology-based pattern prototype for female girdles
Authors: Yao Xiaofeng , Wang Jianping , Liu Kaixuan , Xu Shuo
Published: December 2020

Purpose

An exact pattern prototype is a prerequisite for female girdle pattern-making. The purpose of this paper is to develop new ways to make girdle pattern prototypes based on 3D technology.

Design/methodology/approach

This paper presented two novel methods for creating girdle pattern prototypes. The first one was the girdle's parametric foundation pattern developing method based on 3D geometric modeling. In this method, considering the different characteristics of a female's lower body shape, several models were created to define the relationship between the female's lower body shape and the pattern, such as a side-waist curvature model, an interior-posterior waist-warping model, a buttocks' parametric model and an abdomen parametric model. Then, parameters of drawing the prototype were abstracted to facilitate transforming the 3D geometric model into the 2D pattern. Another method was implemented by 3D virtual modeling and unwrapping. The whole process included surface division, surface reconstruction and surface unwrapping.

Findings

The prototypes created by these two methods were tested using the 3D virtual trying-on examination. Trial tests showed that the patterns can be dressed in the right positions on the virtual model with little pressure. This means that the proportions and shapes of the pattern are correct. The prototypes obtained through the methods proposed in this paper have good effects and high precision. Both methods can be used for making the girdle's foundation pattern.

Originality/value

Two pragmatic approaches of girdle's prototype building have been put forward. The parametric prototype designing method has changed the unconstrained state of free modeling. The pattern structure can be controlled by parameter constraints. In the other method, with 3D scanning and surface modeling technology, personalized girdle's pattern is generated, and the segmentation lines of the girdle can be designed flexibly according to the requirements. These findings also can be used in other tight garments' prototype making.
Assessing residents’ perceptions of urban placemaking prior to hosting a major cultural event
Authors: Wise Nicholas , Đurkin Badurina Jelena , Perić Marko
Published: December 2020

Purpose

More research is needed to consider residents’ perceptions prior to hosting large-scale events. This paper contributes new insight on residents’ perceptions of placemaking analysed by considering awareness, enthusiasm and participation prior to hosting a large-scale event. Placemaking is becoming increasingly important and this insight can help planners understand how locals perceive change and event planning preparations.

Design/methodology/approach

454 residents of Rijeka, Croatia completed a survey (seven-point Likert scale) of 17 placemaking principles, asked in three ways: (1) how you feel; (2) how you believe people near you feel and (3) if you feel that planning/preparing for ECoC 2020 has made a difference. The data analysis considers socio-demographics and the significance of awareness, enthusiasm and participation as factors affecting residents’ perceptions of placemaking.

Findings

The study found respondents originally from Rijeka expressed statistically significant higher level of agreement. Where statistically significant differences exist, female respondents expressed statistically significant higher levels of agreement. For six statements, the distribution of results was not similar for all age groups. Awareness and enthusiasm seems to influence placemaking principles to a greater extent than participation in this study, but all have proven to have statistically significant positive impacts on the placemaking principles assessed.

Practical implications

Planners need to focus on effective promotional activities aimed at awareness and enhance enthusiasm to help increase perceptions of placemaking and increase local quality of life.

Originality/value

explores perceptions of “self” and “how others feel” by assessing principles of placemaking associated with the case of Rijeka. This allows researchers to explore understandings of how people perceive the attitudes of their fellow residents.
Competing corporate sustainability perceptions in a global retail organization
Authors: Elg Ulf , Hultman Jens , Welinder Axel
Published: December 2020

Purpose

The purpose is to explore the different and often contradictory perceptions individual managers have about corporate sustainability within a global retailer.

Design/methodology/approach

A qualitative case study method is used, including interviews and document studies. The authors study the global retailer IKEA. In total the authors have interviewed respondents on both the global level and the country level, within the sustainability organization as well as corporate, sales and communication management. The study includes managers in Sweden, the UK and Germany.

Findings

The research is based on institutional theory, focusing upon cognitive and normative aspects; the authors propose that managers may have a proactive, forceful view on sustainability or a reactive view. These need to coexist. The authors also show how global retailers can balance sustainability goals with other business considerations, as well as about the implications of the sustainability approach for the retailer's business model.

Practical implications

Retail managers need to recognize and integrate the contradictory views on sustainability that managers hold. The authors show how sustainability can be given different impact depending on the context and the strategic issue it is linked to.

Originality/value

Most studies have focused on how sustainability is managed on an organizational level and how different goals can co-exist. The authors’ focus is on individual managers and their perceptions of sustainability – what it includes, how they want to manage sustainability issues, and the priority it should be given.
Big data analytics based enablers of supply chain capabilities and firm competitiveness: a fuzzy-TISM approach
Authors: Bamel Nisha , Bamel Umesh
Published: December 2020

Purpose

This paper aims to identify the big data analytics (BDAs) based enablers of supply chain capabilities (SCCs) and competitiveness of firms. This paper also models the interaction among identified enablers and thus projects the relationship strength of these enablers with SCC and a firm's competitiveness.

Design/methodology/approach

In order to achieve the research objectives of this paper, we employed fuzzy total interpretive structural modeling (TISM), an integrated approach of an interpretive structural model and TISM.

Findings

Results suggest that BDA-based enablers namely, IT infrastructure for BDA; leadership commitment; people skills for use of BDA and financial support for BDA significantly enable SCC and enhance firm competitiveness.

Practical implications

Results of the present study have implications for researchers and practitioners; the results will enable them to design policies around identified enablers of BDA initiatives.

Originality/value

The present paper is one of a few early efforts that address the role of BDA in augmenting SCC and subsequently a firm's competitiveness from a resource-dynamic capability perspective.