bluuebunny/crossref_metadata_2025 huggingface dataset:
Additive, synergic and antagonistic interactions between maternal immune activation and peripubertal stress in cocaine addiction-like behaviour, morphofunctional brain parameters and striatal transcriptome
Authors: Capellán Roberto , Orihuel Javier , Marcos Alberto , Ucha Marcos , Moreno-Fernández Mario , Casquero-Veiga Marta , Soto-Montenegro María Luisa , Desco Manuel , Oteo-Vives Marta , Ibáñez-Moragues Marta , Magro-Calvo Natalia , Morcillo Miguel Ángel , Ambrosio Emilio , Higuera-Matas Alejandro
Published: October 2021

Substance use disorders are more prevalent in schizophrenia, worsening its course and prognosis. Here, we used a double-hit rat model, combining maternal immune activation (MIA) and peripubertal stress (PUS), to study cocaine addiction and the underlying neurobehavioural alterations. We injected lipopolysaccharide or saline on gestational days 15 and 16 to pregnant rats. Their male offspring were then subjected to 5 episodes of unpredictable stress every other day during adolescence (from postnatal day 28 to 38). When rats reached adulthood, we studied cocaine addiction-like behaviour, impulsivity, conditioning processes and several aspects of brain structure and function by MRI, PET and RNAseq. MIA facilitated the acquisition of cocaine self-administration while PUS reduced cocaine intake, an effect that was reversed by MIA. MIA increased motivation for cocaine and reversed the effects of PUS during extended access. Incubation of seeking was unaffected. Neither hit alone nor their combination impacted Pavlovian or instrumental conditioning or impulsiveness. At the brain level, PUS reduced hippocampal volume and hyperactivated the dorsal subiculum. MIA+PUS altered the structure and function of the dorsal striatum increasing its volume and interfering with glutamatergic dynamics. MIA did not affect the gene expression of the nucleus accumbens but, when combined with PUS, modulated specific genes that could account for the restored cocaine intake. PUS had a profound effect on the dorsal striatal transcriptome however, this was obliterated when PUS occurred in animals with MIA. These results describe a complex interplay between MIA and stress on neurodevelopment and in the susceptibility to develop cocaine addiction.
scREMOTE: Using multimodal single cell data to predict regulatory gene relationships and to build a computational cell reprogramming model
Authors: Tran Andy , Yang Pengyi , Yang Jean Y.H. , Ormerod John T.
Published: October 2021

Cell reprogramming offers a potential treatment to many diseases, by regenerating specialized somatic cells. Despite decades of research, discovering the transcription factors that promote cell reprogramming has largely been accomplished through trial and error, a time-consuming and costly method. A computational model for cell reprogramming, however, could guide the hypothesis formulation and experimental validation, to efficiently utilize time and resources. Current methods often cannot account for the heterogeneity observed in cell reprogramming, or they only make short-term predictions, without modelling the entire reprogramming process. Here, we present scREMOTE, a novel computational model for cell reprogramming that leverages single cell multiomics data, enabling a more holistic view of the regulatory mechanisms at cellular resolution. This is achieved by first identifying the regulatory potential of each transcription factor and gene to uncover regulatory relationships, then a regression model is built to estimate the effect of transcription factor perturbations. We show that scREMOTE successfully predicts the long-term effect of overexpressing two key transcription factors in hair follicle development by capturing higher-order gene regulations. Together, this demonstrates that integrating the multimodal processes governing gene regulation creates a more accurate model for cell reprogramming with significant potential to accelerate research in regenerative medicine.
Structural Diversity of Photoswitchable Sphingolipids for Optodynamic Control of Lipid Raft Microdomains
Authors: Hartrampf Nina , Leitao Samuel M. , Winter Nils , Toombs-Ruane Henry , Frank James A. , Schwille Petra , Trauner Dirk , Franquelim Henri G.
Published: October 2021

Sphingolipids are a structurally diverse class of lipids predominantly found in the plasma membrane of eukaryotic cells. These lipids can laterally segregate with other saturated lipids and cholesterol into lipid rafts; liquid-ordered (Lo) microdomains that act as organizing centers within biomembranes. Owing the vital role of sphingolipids for lipid segregation, controlling their lateral localization is of utmost significance. Hence, we made use of the light-induced trans-cis isomerization of azobenzene-modified acyl chains, to develop a set of photoswitchable sphingolipids, with different headgroups (hydroxyl, galactosyl, phosphocholine) and backbones (sphingosine, phytosphingosine, tetrahydropyran (THP)-blocked sphingosine), able to shuttle between liquid-ordered (Lo) and liquid-disordered (Ld) regions of model membranes upon irradiation with UV-A (λ = 365 nm) and blue (λ = 470 nm) light, respectively. Using combined high-speed atomic force microscopy, fluorescence microscopy, and force spectroscopy, we investigated how these active sphingolipids laterally remodel supported bilayers upon photo-isomerization, notably in terms of domain area changes, height mismatch, line tension, and membrane piercing. Hereby, we show that all sphingosine-(Azo-β-Gal-Cer, Azo-SM, Azo-Cer) and phytosphingosine-based (Azo-α-Gal-PhCer, Azo-PhCer) photolipids behave similarly, promoting a reduction in Lo domain area when in the UV-adapted cis-isoform. In contrast, azo-sphingolipids having THP groups that block H-bonding at the sphingosine backbone (Azo-THP-SM, Azo-THP-Cer) induce an increase in the Lo domain area when in cis, accompanied by a major rise in height mismatch and line tension. These changes were fully reversible upon blue light-triggered isomerization of the various lipids back to trans, pinpointing the role of interfacial interactions for the formation of stable Lo lipid raft domains.
PeakBot: Machine learning based chromatographic peak picking
Authors: Bueschl Christoph , Doppler Maria , Varga Elisabeth , Seidl Bernhard , Flasch Mira , Warth Benedikt , Zanghellini Juergen
Published: October 2021

Motivation

Chromatographic peak picking is among the first steps in data processing workflows of raw LC-HRMS datasets in untargeted metabolomics applications. Its performance is crucial for the holistic detection of all metabolic features as well as their relative quantification for statistical analysis and metabolite identification. Random noise, non-baseline separated compounds and unspecific background signals complicate this task.

Results

A machine-learning framework entitled PeakBot was developed for detecting chromatographic peaks in LC-HRMS profile-mode data. It first detects all local signal maxima in a chromatogram, which are then extracted as super-sampled standardized areas (retention-time vs. m/z). These are subsequently inspected by a custom-trained convolutional neural network that forms the basis of PeakBot’s architecture. The model reports if the respective local maximum is the apex of a chromatographic peak or not as well as its peak center and bounding box.

In training and independent validation datasets used for development, PeakBot achieved a high performance with respect to discriminating between chromatographic peaks and background signals (accuracy of 0.99). For training the machine-learning model a minimum of 100 reference features are needed to learn their characteristics to achieve high-quality peak-picking results for detecting such chromatographic peaks in an untargeted fashion.

PeakBot is implemented in python (3.8) and uses the TensorFlow (2.5.0) package for machine-learning related tasks. It has been tested on Linux and Windows OSs.

Availability

The package is available free of charge for non-commercial use (CC BY-NC-SA). It is available at https://github.com/christophuv/PeakBot.

Contact

christoph.bueschl@univie.ac.at

Supplementary information

Supplementary data are available at Bioinformatics online.
Evolution of reduced dormancy during range expansions
Authors: Travis Justin M. J. , Mynard Poppy , Bocedi Greta
Published: October 2021

There is increasing evidence that life-history traits can evolve rapidly during range expansion and that this evolution can impact the ecological dynamics of population spread. While dispersal evolution during range expansion has received substantial attention, dormancy (dispersal in time) has not. Here, we use an individual-based model to investigate the evolution of seed dormancy during range expansion. When a population is at spatial equilibrium our model produces results that are consistent with previous theoretical studies: seed dormancy evolves due to kin competition and the degree of dormancy increases as temporal environmental variation increases. During range expansions we consistently observe evolution towards reduced rates of dormancy at the front. Behind the front there is selection for higher rates of dormancy. Notably, the decreased dormancy towards the expanding margin reduces the regional resilience of recently expanded populations to a series of harsh years. We discuss how dormancy evolution during range expansion, and its consequences for spatial population dynamics, may impact other evolutionary responses to environmental change. We end with suggestions for future theoretical and empirical work.
Dormant replication origin firing links replication stress to whole chromosomal instability in human cancer
Authors: Schmidt Ann-Kathrin , Böhly Nicolas , Zhang Xiaoxiao , Slusarenko Benjamin O. , Hennecke Magdalena , Kschischo Maik , Bastians Holger
Published: October 2021

Chromosomal instability (CIN) is a hallmark of cancer and comprises structural CIN (S-CIN) and whole chromosome instability (W-CIN). Replication stress (RS), a condition of slowed or stalled DNA replication during S phase, has been linked to S-CIN, whereas defects in mitosis leading to chromosome missegregation and aneuploidy can account for W-CIN. It is well established that RS can activate additional replication origin firing that is considered as a rescue mechanism to suppress chromosomal instability in the presence of RS. In contrast, we show here that an increase in replication origin firing during S phase can contribute to W-CIN in human cancer cells. Increased origin firing can be specifically triggered by overexpression of origin firing genes including GINS1 and CDC45, whose elevated expression significantly correlates with W-CIN in human cancer specimens. Moreover, endogenous mild RS present in cancer cells characterized by W-CIN or modulation of the origin firing regulating ATR-CDK1-RIF1 axis induces dormant origin firing, which is sufficient to trigger chromosome missegregation and W-CIN. Importantly, chromosome missegregation upon increased dormant origin firing is mediated by increased microtubule growth rates leading to the generation of lagging chromosomes in mitosis, a condition prevalent in chromosomally unstable cancer cells. Thus, our study identified increased or dormant replication origin firing as a hitherto unrecognized, but cancer-relevant trigger for chromosomal instability.
Unravelling the complex genetic basis of growth in New Zealand silver trevally (Pseudocaranx georgianus)
Authors: Valenza-Troubat Noemie , Montanari Sara , Ritchie Peter , Wellenreuther Maren
Published: October 2021

Growth directly influences production rate and therefore is one of the most important and well-studied trait in animal breeding. However, understanding the genetic basis of growth has been hindered by its typically complex polygenic architecture. Here, we performed quantitative trait locus (QTL) mapping and genome-wide association studies (GWAS) for 10 growth traits that were observed over two years in 1,100 F1captive-bred trevally (Pseudocaranx georgianus). We constructed the first high-density linkage map for trevally, which included 19,861 single nucleotide polymorphism (SNP) markers, and discovered eight QTLs for height, length and weight on linkage groups 3, 14 and 18. Using GWAS, we further identified 113 SNP-trait associations, uncovering 10 genetic hot spots involved in growth. Two of the markers found in the GWAS co-located with the QTLs previously mentioned, demonstrating that combining QTL mapping and GWAS represents a powerful approach for the identification and validation of loci controlling complex traits. This is the first study of its kind for trevally. Our findings provide important insights into the genetic architecture of growth in this species and supply a basis for fine mapping QTLs, marker-assisted selection, and further detailed functional analysis of the genes underlying growth in trevally.
FX-Cell: Quantitative cell release from fixed plant tissues for single-cell genomics
Authors: Marchant D. Blaine , Nelms Brad , Walbot Virginia
Published: October 2021

Single-cell RNA-sequencing (scRNA-seq) can provide invaluable insight into cell development, cell type identification, and plant evolution. However, the resilience of the cell wall makes it difficult to dissociate plant tissues and release individual cells for single-cell analysis. Here, we show that plant organs can be rapidly and quantitatively dissociated into cells if fixed prior to enzymatic digestion. Fixation enables digestion at high temperatures at which enzymatic activity is optimal and stabilizes the plant cell cytoplasm, rendering cells resistant to mechanical shear force while maintaining high quality RNA. This protocol, FX-Cell, releases four to ten-fold more recoverable cells than optimized protoplasting methods applied to maize anthers or root tips with no cell type biases and can be readily applied to a variety of plant taxa and tissues with no optimization. FX-Cell and scRNA-seq analysis were applied to maize anthers for which 95% of the cells were dispersed and provided suitable scRNA-seq data for the identification of anther cell types with marker genes and well-understood biological functions, including rare meiocytes (∼1% anther cells). In addition, the scRNA-seq data provided putative marker genes and gene ontology information for the identification of unknown cell types. FX-Cell also preserves the morphology of the isolated cells, permitting cell type identification without staining. Ultimately, FX-Cell can be applied to a range of plant species and tissues with minimal to no optimization paving the way for plant scRNA-seq analyses in non-model taxa and tissues.
Multi-layer Regulation of Rubisco in Response to Altered Carbon Status in Synechococcus elongatus PCC 7942
Authors: Singh Amit K. , Santos-Merino María , Sakkos Jonathan K. , Walker Berkley J. , Ducat Daniel C
Published: October 2021

Photosynthetic organisms possess a variety of mechanisms to achieve balance between absorbed light (source) and the capacity to metabolically utilize or dissipate this energy (sink). While regulatory processes that detect changes in metabolic status/balance are relatively well-studied in plants, analogous pathways remain poorly characterized in photosynthetic microbes. Herein, we explore systemic changes that result from alterations in carbon availability in the model cyanobacterium Synechococcus elongatus PCC 7942 by taking advantage of an engineered strain where influx/efflux of a central carbon metabolite, sucrose, can be regulated experimentally. We observe that induction of a high-flux sucrose export pathway leads to depletion of internal carbon storage pools (glycogen), and concurrent increases in photosynthetic parameters. Further, a proteome-wide analysis and fluorescence reporter-based analysis revealed that upregulated factors following the activation of the metabolic sink are strongly concentrated on ribulose-1,5-bisphosphate carboxylase-oxygenase (Rubisco) and axillary modules involved in Rubisco maturation. Carboxysome number and Rubisco activity also increase following engagement of sucrose secretion. Conversely, reversing the flux of sucrose by feeding exogenous sucrose heterologously results in increased glycogen pools, decreased Rubisco abundance, decreased photosystem II quantum efficiency, and carboxysome reorganization. Our data suggest that Rubisco activity and organization are key outputs connected to regulatory pathways involved in metabolic balancing in cyanobacteria.

One sentence summary

Rubisco activity and organization are key outputs involve in source-sink balancing in cyanobacteria.
A Phytochrome B-PIF4-MYC2 Module Tunes Secondary Cell Wall Thickening in Response to Shaded Lighting
Authors: Luo Fang , Zhang Qian , Xin Hu , Liu Hongtao , Yang Hong-Quan , Doblin Monika S , Bacic Antony , Li Laigeng
Published: October 2021

Secondary cell walls (SCW) in stem xylem cells provide mechanical strength and structural support for growth. SCW thickening is light- regulated and varies under different light growth conditions. Our previous study revealed that blue light enhances SCW thickening through the activity of MYC2 directed by CRYPTOCHROME1 (CRY1) signaling in stem xylary fiber cells. In this study, we demonstrate that the low ratio of red: far-red light (R:FR) of the shaded light condition inhibits SCW thickening in the inflorescence stem of Arabidopsis. Phytochrome B (PHYB) plays a dominant role in perceiving the R:FR balance. Under white and red-light conditions, phyB mutants display thinner SCWs in xylary fibers, but thicker SCWs are deposited in the PHYTOCHROME INTERACTING FACTORS (PIFs) quadruple mutant pif1pif3pif4pif5 (pifq), suggesting involvement of the PHYB-PIFs signaling module in regulating SCW thickening. Interaction of PIF4 with MYC2 affects MYC2 localization in nuclei and inhibits its transactivation activity on the NST1 promoter. Shade conditions mediate the PIF4 interaction with MYC2 to regulate SCW thickening. Genetic analysis confirms that the regulation of SCW thickening by PIFs is dependent on MYC2 function. Together, these data reveal a molecular mechanism for the effect of shaded light inhibition on SCW thickening in stems of Arabidopsis.
Spatial regulation of AMPK signaling revealed by a sensitive kinase activity reporter
Authors: Schmitt Danielle L. , Curtis Stephanie D. , Leung Allen , Zhang Jin-fan , Chen Mingyuan , He Catherine Y. , Mehta Sohum , Rangamani Padmini , Shaw Reuben J. , Zhang Jin
Published: October 2021

AMP-activated protein kinase (AMPK) is a master regulator of cellular energetics which coordinates metabolism by phosphorylating a plethora of substrates throughout the cell. But whether AMPK activity is regulated at different subcellular locations to provide precise spatial and temporal control over metabolism is unclear. Genetically encoded AMPK activity reporters (AMPKAR) have provided a window into spatial AMPK activity, but the limited dynamic range of current AMPKARs hinders detailed study. To monitor the dynamic activity of AMPK with high sensitivity, we developed a single-fluorophore AMPK activity reporter (ExRai AMPKAR) that exhibits an excitation ratiometric fluorescence change upon phosphorylation by AMPK, with over 3-fold greater response compared to previous AMPKARs. Using subcellularly localized ExRai AMPKAR, we found that the activity of AMPK at the lysosome and mitochondria are differentially regulated. While different activating conditions, irrespective of their effects on ATP, robustly yet gradually increase mitochondrial AMPK activity, lysosomal AMPK activity accumulates with much faster kinetics. Genetic deletion of the canonical upstream kinase liver kinase B1 (LKB1) resulted in slower AMPK activity at lysosomes but did not affect the response amplitude at either location, in sharp contrast to the necessity of LKB1 for maximal cytoplasmic AMPK activity. We further discovered AMPK activity in the nucleus, which resulted from LKB1-mediated cytoplasmic activation of AMPK followed by nuclear shuttling. Thus, a new, sensitive reporter for AMPK activity, ExRai AMPKAR, in complement with mathematical and biophysical methods, captured subcellular AMPK activity dynamics in living cells and unveiled complex regulation of AMPK signaling within subcellular compartments.
HORmon: automated annotation of human centromeres
Authors: Kunyavskaya Olga , Dvorkina Tatiana , Bzikadze Andrey V. , Alexandrov Ivan A. , Pevzner Pavel A.
Published: October 2021

Recent advances in long-read sequencing opened a possibility to address the long-standing questions about the architecture and evolution of human centromeres. They also emphasized the need for centromere annotation (partitioning human centromeres into monomers and higher-order repeats (HORs)). Even though there was a half-century-long series of semi-manual studies of centromere architecture, a rigorous centromere annotation algorithm is still lacking. Moreover, an automated centromere annotation is a prerequisite for studies of genetic diseases associated with centromeres, and evolutionary studies of centromeres across multiple species. Although the monomer decomposition (transforming a centromere into a monocentromere written in the monomer alphabet) and the HOR decomposition (representing a monocentromere in the alphabet of HORs) are currently viewed as two separate problems, we demonstrate that they should be integrated into a single framework in such a way that HOR (monomer) inference affects monomer (HOR) inference. We thus developed the HORmon algorithm that integrates the monomer/HOR inference and automatically generates the human monomers/HORs that are largely consistent with the previous semi-manual inference.
Engaging Europe’s employees: a complex problem with a simple solution
Authors: Sinyan Pa , Nink Marco
Published: October 2021

Purpose

This paper aims to establish the state of employee engagement levels in Europe and offer insights into the reasons behind the current state of affairs. It proposes that management matters most out of all the factors influencing employee engagement, and that European organisations should therefore invest in equipping their leadership teams to provide employees with a positive experience of the workplace.

Design/methodology/approach

This paper uses data from the Gallup World Poll, which Gallup has used to conduct surveys of the world’s adult population, using randomly selected samples, since 2005. Covering more than 160 countries since its inception, the survey was conducted via computer-assisted telephone interviews in 2020 to account for COVID-compliant safety measures.

Findings

This paper provides insights into the engagement levels of European employees, which remained dismally low in 2020 as it has for the last decade. By far, the biggest influence on the state of employee engagement is leadership, which will require improvement if European organisations are to improve their employee engagement levels.

Originality/value

This paper fulfils the need for organisations to gain a better understanding of how to improve their employee engagement levels in the wake of a significant global crisis. Inspiring workplace cultures that maximise the well-being of every employee can help to reverse the decline of economic dynamism across the globe.
Reimagining This Creature: Hospitality and Autohagiography in the Visions of Margery Kempe
Authors: Fitzpatrick Joan
Published: October 2021

The Book of Margery Kempe tells the apparently true story of a medieval wife and mother of fourteen children who, following religious conversion, leaves her old life behind in order to dedicate herself to God. Apparently dictated to scribes by Kempe herself, the Book traces her treatment at the hands of her contemporaries, many of them hostile to her claims of religious visions and her odd behaviour as a result. While there has been some critical work done on the significance of food and drink in the Book, little has been observed about the role of food and drink in Kempe's visions. Specifically, critics have hitherto overlooked how it is via food, drink and performing the role of hostess in her visions that Kempe presented herself as an active and valuable participant in the Christian narrative and thus worthy of sainthood. Kempe is often unfavourably compared to Julian of Norwich, the calm and intellectual mystic who lived the solitary and dignified life of the anchoress. This article argues that the two women are more alike than is usually acknowledged. Kempe too withdrew from the world in her visions, in order to play a role in the Christian story and so promote her special status as a holy woman and her own narrative as a work of late medieval autohagiography.
Water‐assisted cold isostatic pressing to enhance sinterability of alumina ceramics
Authors: Kermani Milad , Pouchly Vaclav , Lin Yong , Hu Chunfeng , Grasso Salvatore
Published: October 2021

Water‐Assisted cold isostatic Pressing (WAP) enabled pressure‐less sintering of fine grained (0.6 μm) and nearly full dense (99.3%) weakly translucent alumina ceramics. As a term of comparison, Dry Pressed (DP) samples, prepared under identical processing conditions, maintained an opaque appearance, and their relative density did not exceed 97.7%. The enhanced compaction of WAP allowed to lower the sintering temperature down to 1350°C, which is approximately 100–150°C lower than that of DP powder. WAP samples resulted in an apparent activation energy for sintering (640 kJ/mol) matching literature values, confirming that the enhanced sinterability was attributed to an improved green density rather than a change in sintering mechanisms.
Creatinine reduction ratio on postoperative day 2 predicts long‐term outcomes after living donor kidney transplantation
Authors: Kinoshita Yoshitaka , Katano Saki , Nishida Sho , Shimizu Toshihiro , Fujimura Tetsuya , Kume Haruki , Iwami Daiki
Published: October 2021

Objectives

To evaluate the relationship between the creatinine reduction ratio between postoperative days 1 and 2 and post‐transplantation clinical outcomes after living donor kidney transplantation.

Methods

Clinical data of patients who underwent living donor kidney transplantation at Jichi Medical University Hospital, Tochigi, Japan, between 2006 and 2019 were retrieved. The creatinine reduction ratio between postoperative days 1 and 2 was calculated based on the formula: (Cre1 − Cre2) × 100/Cre1; patients were then classified into either the slow graft function (creatinine reduction ratio between postoperative days 1 and 2 ≤30%) or immediate graft function (creatinine reduction ratio between postoperative days 1 and 2 >30%) group. We carried out the log‐rank test and multivariate Cox proportional hazards regression analyses to assess graft survival and rejection‐free survival, and the unpaired t‐test and multivariate linear regression to assess post‐transplantation estimated glomerular filtration rates. Multivariate analyses used age, sex, dialysis duration, ABO compatibility, donor‐specific antibody positivity and medically complex living donors as explanatory variables.

Results

Of the 272 patients, 30 and 242 were in the slow graft function and immediate graft function groups, respectively. Multivariate Cox proportional hazards regression analyses showed a significantly higher incidence of overall and death‐censored graft loss in the slow graft function group than the immediate graft function group. The frequency of rejection after 1 week post‐transplantation did not differ within the groups. Post‐transplantation estimated glomerular filtration rates tended to decline earlier in the slow graft function group than in the immediate graft function group; however, the difference was not statistically significant.

Conclusions

The creatinine reduction ratio between postoperative days 1 and 2 could potentially predict long‐term outcomes after living donor kidney transplantation. Using the creatinine reduction ratio between postoperative days 1 and 2 and other conventional indicators might allow accurate risk classification and appropriate therapeutic interventions.
Anti‐microtubule activity of the traditional Chinese medicine herb Northern Ban Lan (Isatis tinctoria) leads to glucobrassicin
Authors: Guan Pingyin , Zhou Jianning , Girel Sergey , Zhu Xin , Schwab Marian , Zhang Kunxi , Wang‐Müller Qiyan , Bigler Laurent , Nick Peter
Published: October 2021

Traditional Chinese medicine (TCM) belongs to the most elaborate and extensive systems of plant‐based healing. The herb Northern Ban Lan (Isatis tinctoria) is famous for its antiviral and anti‐inflammatory activity. Although numerous components isolated from I. tinctoria have been characterized so far, their modes of action have remained unclear. Here, we show that extracts from I. tinctoria exert anti‐microtubular activity. Using time‐lapse microscopy in living tobacco BY‐2 (Nicotiana tabacum L. cv Bright Yellow 2) cells expressing green fluorescent protein‐tubulin, we use activity‐guided fractionation to screen out the biologically active compounds of I. tinctoria. Among 54 fractions obtained from either leaves or roots of I. tinctoria by methanol (MeOH/H2O 8:2), or ethyl acetate extraction, one specific methanolic root fraction was selected, because it efficiently and rapidly eliminated microtubules. By combination of further purification with ultra‐high‐performance liquid chromatography and high‐resolution tandem mass spectrometry most of the bioactivity could be assigned to the glucosinolate compound glucobrassicin. Glucobrassicin can also affect microtubules and induce apoptosis in HeLa cells. In the light of these findings, the antiviral activity of Northern Ban Lan is discussed in the context of microtubules being hijacked by many viral pathogens for cell‐to‐cell spread.
A prospective randomized controlled trial of Q‐switched Nd:YAG laser with topical 3% tranexamic acid (TA) versus microneedling with topical 3% tranexamic acid (TA) in treatment of melasma
Authors: Debasmita Behera , Raj Chinmoy , Ishan Agrawal , Ipsita Debata
Published: October 2021

Introduction

Treatment of melasma is challenging. Topical TA has shown promising results as an adjuvant, when combined with microneedling or QS Nd:YAG laser. The efficacy of both combinations has been demonstrated but the efficacy between these two combinations has never been compared.

Aim and Objectives

To compare the efficacy and side effects of microneedling and QS Nd:YAG laser when combined with topical 3% TA gel.

Materials and Methods

60 patients were randomized into 2 groups. Group A received Nd:YAG laser sessions monthly with daily 3% TA gel while Group B underwent microneedling monthly with daily 3% TA gel. A total of 5 sessions were given with follow‐up after 2 months. Evaluation using modified Melasma Area and Severity Index (mMASI), Patient satisfaction score, and photography was done at baseline, 3rd session, 5th session, and final follow‐up.

Results

Mean fall in mMASI at follow‐up in Group A was 5.12 ± 2.66 to 2.33 ± 1.33 and Group B was 4.60 ± 2.38 to 1.88 ± 1.08 (p < 0.001). Patient satisfaction score was not significantly different. Side effects of both interventions included erythema, pain, and burning sensation.

Conclusion

Our study shows equal efficacy of microneedling and QS Nd:YAG laser when combined with topical 3% TA gel in treating melasma without serious side effects. Microneedling has more downtime and maybe less preferable as a lunchtime procedure.
Impact of an oral gonadotropin‐releasing hormone antagonist on severe ovarian hyperstimulation syndrome in a patient with breast cancer who received a sustained‐release gonadotropin‐releasing hormone agonist: A case report
Authors: Hanada Tetsuro , Kimura Fuminori , Kitazawa Jun , Morimune Aina , Murakami Takashi
Published: October 2021

Postoperative hormone therapy for hormone‐sensitive patients with breast cancer is important to prevent a recurrence. As hormone therapy does not induce infertility in patients, fertility‐preserving therapy is not provided during treatment. Here, however, we performed controlled ovarian stimulation and embryo freezing for fertility preservation under the influence of a sustained‐release gonadotropin‐releasing hormone agonist in a patient with breast cancer whose postoperative treatment plan was changed from hormone therapy to chemotherapy. After oocyte retrieval, the patient developed treatment‐resistant severe symptomatic ovarian hyperstimulation syndrome. Following treatment with oral gonadotropin‐releasing hormone antagonist, her symptoms immediately improved, and she could receive chemotherapy on schedule.
Eleven angry men
Authors: Littlejohn Clayton
Published: October 2021

While many of us would not want to abandon the requirement that a defendant can only be found guilty of a serious criminal offence by a unanimous jury, we should not expect epistemology to give us the resources we need for justifying this requirement. The doubts that might prevent jurors from reaching unanimity do not show that, say, the BARD standard has not been met. Even if it were true, as some have suggested, that rationality requires that a jury composed of epistemic peers should coalesce around one view about the defendant's guilt, the failure to reach unanimity might be a good reason to worry about the epistemic failings of some small number of jurors but no reason to worry that we've failed to protect the defendant from an unjustified imposition of, say, the risk against wrongful conviction. The arguments for the unanimity requirement will need to come from outside of epistemology.
Failure Mode Determination of American Petroleum Institute 12F Shop-Welded Tanks With a New Roof-to-Shell Junction Detail
Authors: Feng Heyi , Guzey Sukru
Published: October 2021

The American Petroleum Institute (API) 12F is the specification for vertical, aboveground shop-welded storage tanks published by the API. The nominal capacity for the twelve tank designs given in the current 13th edition of API 12F ranges from 90 bbl. (14.3 m3) to 1000 bbl. (159 m3). The minimum required component thickness and design pressure levels are also provided in the latest edition. This study is a part of a series research project sponsored by API that dedicates to ensure the safe operation of API 12 series storage tanks. In this study, the twelve API 12F tank designs presented in the latest edition are studied. The elastic stress analysis was conducted following the procedures presented in the ASME Boiler and Pressure Vessel Code 2019, Section VIII, Division 2 (ASME VIII-2). The stress levels at the top, bottom, and cleanout junctions subject to the design pressures are determined through finite element analysis (FEA). The bottom uplift subjected to design pressures are obtained, and the yielding pressure at the roof-shell and shell-bottom junctions are also determined. The specific gravity of the stored liquid is raised from 1.0 to 1.2 in this study. A new roof-shell attachment detail is proposed, and a 0.01 in. (0.254 mm) gap between the bottom shell course and the bottom plate is modeled to simulate the actual construction details. In addition, the flat-top rectangular cleanout presented in the current edition of API 12F is modeled. Moreover, various thickness combinations are considered to further investigate the effect due to different component thicknesses.
Boiling Enhanced Lidded Server Packages for Two-Phase Immersion Cooling Using Three-Dimensional Metal Printing and Metal Injection Molding Technologies
Authors: Chuang Jimmy , Yang Jin , Shia David , Li Y. L.
Published: October 2021

In order to meet the increasing performance demand of high-performance computing and edge computing, thermal design power (TDP) of central processing unit (CPU) and graphics processing unit (GPU) needs to increase. This creates thermal challenge to corresponding electronic packages with respect to heat dissipation. In order to address this challenge, two-phase immersion cooling is gaining attention as its primary mode of heat of removal is via liquid-to-vapor phase change, which can occur at relatively low and constant temperatures. In this paper, an integrated heat spreader (IHS) with boiling enhancement features is proposed. Three-dimensional metal printing and metal injection molding (MIM) are the two approaches used to manufacture the new IHS. The resultant IHS with boiling enhancement features is used to build thermal test vehicles (TTV) by following the standard electronic package assembly process. Experimental results demonstrate that boiling enhanced TVs improved two-phase immersion cooling capability by over 50% as compared to baseline TTV without boiling enhanced features.
Underwater acoustic target recognition using attention-based deep neural network
Authors: Xiao Xu , Wang Wenbo , Ren Qunyan , Gerstoft Peter , Ma Li
Published: October 2021

Underwater acoustic target recognition based on ship-radiated noise is difficult owing to the complex marine environment and the interference by multiple targets. As an important technology for target recognition, deep-learning has high accuracy but poor interpretability. In this study, an attention-based neural network (ABNN) is proposed for target recognition in the pressure spectrogram with multi-source interference using an attention module to inspect the inner workings of the neural network. From data obtained during a September 2020 sea trial, the ABNN exhibited a gradual focus on the frequency-domain feature of the target ship and suppressed environmental noises and marine vessel interference, which led to high accuracy in the target detection and recognition.
‘Ending AIDS’ movement falters worldwide
Authors: Cohen Jon
Published: October 2021

But studies confirm treatment can slow infections in entire communities.
The Cyclin Cln1 Controls Polyploid Titan Cell Formation following a Stress-Induced G
2
Arrest in Cryptococcus
Authors: Altamirano Sophie , Li Zhongming , Fu Man Shun , Ding Minna , Fulton Sophie R. , Yoder J. Marina , Tran Vy , Nielsen Kirsten
Published: October 2021

Dysregulation of the cell cycle underlies many human genetic diseases and cancers, yet numerous organisms, including microbes, also manipulate the cell cycle to generate both morphologic and genetic diversity as a natural mechanism to enhance their chances for survival. The eukaryotic pathogen
Cryptococcus neoformans
generates morphologically distinct polyploid titan cells critical for host adaptation and subsequent disease.
Supplemental Material: Putative fossils of chemotrophic microbes preserved in seep carbonates from Vestnesa Ridge, off northwest Svalbard, Norway
Authors: Himmler Tobias , al. et
Published: October 2021

Detailed methods, supplemental figures showing microfacies context of microstructures and nanoSIMS data correlation plots, as well as supplemental data file including nanoSIMS data, lipid biomarker data, mineralogy, and carbonate stable carbon and oxygen isotope compositions.
‘Stay home when sick’ advice: implications for sport and exercise
Authors: Orchard John W , Orchard Jessica J , Puranik Rajesh
Published: October 2021

The coronavirus pandemic has given everyone in society an education on the harms of spread of respiratory illness. Young healthy athletes are far less likely to suffer severe adverse consequences of viral illnesses than the elderly and frail, but they are not completely immune. Chronic fatigue (overtraining) is an uncommon outcome and myocarditis a rare one, but they both warrant due consideration. It is, therefore, a sensible individual strategy to ‘stay home when sick’ if only for these risks. Traditionally though, athletes have tended to push through (train and play when ill) because of competing concerns, such as key events/matches and ‘not wanting to let teammates down’. Data from both low COVID-19 and high COVID-19 countries show that the number of cardiovascular deaths in a society correlates with the number of respiratory deaths at the same time, further linking respiratory viruses to cardiovascular deaths. We are now more aware of public health obligations to prevent the spread of respiratory illnesses, in particular to protect the more vulnerable members the community. This hopefully will correspond with a change in the culture of sport to one where it is considered ‘the right thing to do’, to ‘stay home when sick’.
Spectroscopic and electrochemical approaches for the analysis of interaction between textile dye 231 and salmon sperm DNA
Authors: El-Shobaky Amira , Elshafey Reda , Radi Abd-Elgawad
Published: October 2021

DNA is one of the most critical targets for many artificial agents listed as carcinogens. Most of them irreversibly bind to the DNA and induce genome mutation; therefore, it is vital to study the nature of binding of these molecules to anticipate their toxicity. The interaction between the textile dye reactive red 231 and salmon sperm double-stranded DNA (ss-dsDNA) was investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV), and ultraviolet-visible spectroscopy (UV–vis spectroscopy). Changes in the anodic current signals of the dye were observed in the presence and absence of ss-dsDNA at a glassy carbon electrode (GCE) using CV. The diffusion coefficient (D) was found to be 2.2 × 10–7 and 9.5 × 10–8 cm2 s−1 from the CV data for the free dye and dye-DNA complex, respectively. Electrochemical and UV–vis spectroscopy indicated 1:1 complex formation of the dye with DNA. The binding constant (kb) between the dye and DNA was calculated to be 5.4 × 105 M–1 and 4.9 × 105 M–1 at pH 4.0 using CV and UV–vis spectroscopy, respectively. Overall, these results suggest that the dye binds to DNA through the combined effect of intercalation and electrostatic interactions. DNA damage was also detected through changes in the voltammetric behaviour of the dye.
Performance study of the relative decay width measurement in hadronic decays of Z boson at CEPC by using the template method
Authors: Li Bo , Du Yanyan , Liang Zhijun , Liu Bo
Published: October 2021

The Circular Electron Positron Collider (CEPC) was proposed by the Chinese particle physics scientists as a future Higgs factory and [Formula: see text] factory. It will produced more than [Formula: see text] [Formula: see text] bosons by operating at a center-of-mass energy around 91.2 GeV in two years. In this study, the measurement of the relative decay widths of [Formula: see text] bosons decaying to [Formula: see text] quarks [Formula: see text], [Formula: see text] quarks [Formula: see text] and light quarks [Formula: see text] in hadronic [Formula: see text] decays are studied on CEPC Monte Carlo (MC) samples. By using a template method, [Formula: see text], [Formula: see text] and [Formula: see text] can be fitted from reconstructed data as the fractions of MC templates with different flavors. The distribution of a sensitive variable, [Formula: see text]-tagging probability, is used as the template, because of its high performance in discriminating different flavors. Based on the expected statistics of [Formula: see text] [Formula: see text] bosons at CEPC, the statistical uncertainty is estimated to be approximately [Formula: see text] by using the template method, which means that the measurement will no longer be limited by the statistics. Systematic errors arise directly from the difference in the [Formula: see text]-tagging probability distribution between real data and template MC samples. By considering the bias of input variables used for [Formula: see text]-tagging probability computing, the quantitative effect for each kind of input variable is investigated by using an ensemble test procedure.
Semi-analytic treatment of mixed hyperbolic–elliptic Cauchy problem modeling three-phase flow in porous media
Authors: Az-Zo’bi Emad , Yildirim Ahmet , Akinyemi Lanre
Published: October 2021

This work provides a technical applied description of the residual power series method (RPSM) to develop a fast and accurate algorithm for mixed hyperbolic–elliptic systems of conservation laws with Riemann initial datum. The RPSM does not require discretization, reduces the system to an explicit system of algebraic equations and consequently of massive and complex computations, and provides the solution in a form of Taylor power series expansion of closed-form exact solution (if exists). Theoretically, convergence hypotheses are discussed, and error bounds of exponential rates are derived. Numerically, the convergence and stability of approximate solutions are achieved for systems of mixed type. The reported results, with application to general Cauchy problems, which rise in diverse branches of physics and engineering, reveal the reliability, efficiency, and economical implementation of the proposed algorithm for handling nonlinear partial differential equations in applied mathematics.
Cytotoxicity and pro-inflammatory effect of GaSb thin films in L929 cells
Authors: Fujihara Junko , Nishimoto Naoki
Published: October 2021

Gallium antimonide (GaSb)-based devices operate efficiently in the infrared region. Investigating the toxicity of GaSb thin film is necessary for using embedded GaSb-based devices in living organisms. In this study, viability, oxidative stress, inflammatory responses, apoptosis induction and genotoxicity of GaSb were assayed using L929 cells following a 24 h exposure to GaSb. GaSb thin films were deposited on a quartz substrate using radio frequency (RF) magnetron sputtering. These films were soaked in cell culture medium to prepare test solutions. The viability of cells treated with the GaSb extract was lower than that of control cells. GaSb elicited little reactive oxygen species (ROS) generation. Tumor necrosis factor (TNF)-[Formula: see text] and interleukin (IL)-1[Formula: see text] levels were elevated in GaSb-treated cell culture supernatants. Apoptosis and genotoxicity were not evident following GaSb treatment. Overall, these results demonstrate the low toxicity of GaSb compared with previous studies examining arsenic-containing III–V materials, which is desirable for biological devices.
Parton evolution time-dependent transverse shape asymmetry in peripheral Pb–Pb and p–Pb collisions at 5.02TeV
Authors: Wei De-Xian
Published: October 2021

In this paper, we use a multi-phase transport model to simulate the parton evolution time-dependent transverse asymmetry in peripheral Pb–Pb ([Formula: see text]–15[Formula: see text]fm) and p–Pb ([Formula: see text]–1[Formula: see text]fm) collisions at [Formula: see text][Formula: see text]TeV, respectively. The simulated results showed that the initial spatial asymmetry depends on the collision system, while both the initial momentum asymmetry and final momentum asymmetry are independent on the collision system. It is also shown that the final momentum asymmetry is similar to the initial momentum asymmetry. Furthermore, the averaged transverse shape asymmetry, which includes the initial spatial asymmetry, the initial momentum asymmetry, and the final momentum asymmetry, is significantly dependent on the transverse momentum and particle species identity (PID). The PID scales ordering transverse asymmetry indicated that it provides a possible observation for studying the fluctuating droplet properties of quark–gluon plasma, which may produce in heavy-ion collisions.