bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modified SIR-model applied to covid-19, similarity solutions and projections to further development
Authors: Rebhan E. 
Published: August 2020

AbstractThe SIR-model is adapted to the covid-19 pandemic through a modification that consists in making the basic reproduction number variable. Independent of it, another reproduction number is introduced, which is defined similarly to the usual net reproduction number. Due to its simple analytic form, it enables a clear interpretation for all values. A further parameter, provisionally called acceleration parameter, is introduced and applied, which enables a more differentiated characterization of the infection number dynamics. By a variable transformation the 3 equations of the modified SIR-model can be reduced to 2. The latter are solved up to ordinary integrations. The solutions are evaluated for current situations, yielding a pretty good match with the data reported. Encouraged by this, a variety of possible future developments is examined, including linear and exponential growth of the infection numbers as well as sub- and super-exponential growth. In particular, the behavior of the two reproduction numbers and the acceleration parameter is studied, which in some cases leads to surprising results. With regard to the number of unreported infections it is shown, that from the solution for a special one solutions for others can be derived by similarity transformations.
Molecular Parallelism Underlies Convergent Highland Adaptation of Maize Landraces
Authors: Wang Li , Josephs Emily B. , Lee Kristin M. , Roberts Lucas M. , Rellán-Álvarez Rubén , Ross-Ibarra Jeffrey , Hufford Matthew B. 
Published: August 2020

AbstractConvergent phenotypic evolution provides some of the strongest evidence for adaptation. However, the extent to which recurrent phenotypic adaptation has arisen via parallelism at the molecular level remains unresolved, as does the evolutionary origin of alleles underlying such adaptation. Here, we investigate genetic mechanisms of convergent highland adaptation in maize landrace populations and evaluate the genetic sources of recurrently selected alleles. Population branch excess statistics reveal strong evidence of parallel adaptation at the level of individual SNPs, genes and pathways in four independent highland maize populations, even though most SNPs show unique patterns of local adaptation. The majority of selected SNPs originated via migration from a single population, most likely in the Mesoamerican highlands. Polygenic adaptation analyses of quantitative traits reveal that alleles affecting flowering time are significantly associated with elevation, indicating the flowering time pathway was targeted by highland adaptation. In addition, repeatedly selected genes were significantly enriched in the flowering time pathway, indicating their significance in adapting to highland conditions. Overall, our study system represents a promising model to study convergent evolution in plants with potential applications to crop adaptation across environmental gradients.
Respiration and brain neural dynamics associated with interval timing during odor fear learning in rats
Authors: Dupin Maryne , Garcia Samuel , Messaoudi Belkacem , Doyère Valérie , Mouly Anne-Marie 
Published: August 2020

ABSTRACTIn fear conditioning, where a conditioned stimulus predicts the arrival of an aversive stimulus, the animal encodes the time interval between the two stimuli. Freezing, the most used index to assess learned fear, lacks the temporal resolution required to investigate interval timing at the early stages of learning. Here we monitored respiration to visualize anticipatory behavioral responses in an odor fear conditioning in rats, while recording theta (5-15Hz) and gamma (40-80Hz) brain oscillatory activities in the medial prefrontal cortex (mPFC), basolateral amygdala (BLA), dorsomedial striatum (DMS) and olfactory piriform cortex (PIR). We investigated the temporal patterns of respiration frequency and of theta and gamma activity power during the odor-shock interval. We found that akin to respiration patterns, theta temporal curves were modulated by the duration of the odor-shock interval in the four recording sites, and respected scalar property in mPFC and DMS. In contrast, gamma temporal curves were modulated by the interval duration only in the mPFC, and in a manner that did not respect scalar property. This suggests a preferential role for theta rhythm in interval timing. In addition, our data bring the novel idea that the respiratory rhythm might take part in the setting of theta activity dynamics.
Behavioural and transcriptomic characterization of the comorbidity between Alzheimer’s disease and Major Depression
Authors: Martín-Sánchez Ana , Piñero Janet , Nonell Lara , Arnal Magdalena , Ribe Elena M. , Nevado-Holgado Alejo , Lovestone Simon , Sanz Ferran , Furlong Laura I. , Valverde Olga 
Published: August 2020

ABSTRACTMajor Depression (MD) is the most prevalent psychiatric disease in the population and is considered a prodromal stage of the Alzheimer’s disease (AD). Despite both diseases having a robust genetic component, the common transcriptomic signature remains unknown. In this regard, we investigated the cognitive and emotional responses in 3- and 6-month-old in APP/PSEN1-Tg mutant mice, before β-amyloid plaques were detected. Then, we studied the deregulation of genes and pathways in prefrontal cortex, striatum, hippocampus and amygdala, using transcriptomic and functional data analysis. The results demonstrated that depressive-like and anxiety-like behaviours, as well as memory impairments are already present at 3-month-old together with the deregulation of several genes and gene sets, including components of the circadian rhythms, electronic transport chain and neurotransmission. Finally, DisGeNET GSEA provides translational support for common depregulated gene sets related to MD and AD. Altogether, the results demonstrate that MD could be an early manifestation of AD.
Rapid Inactivation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) by Tungsten Trioxide-Based (WO3) Photocatalysis
Authors: Ghezzi Silvia , Pagani Isabel , Poli Guido , Perboni Stefano , Vicenzi Elisa 
Published: August 2020

AbstractSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiological agent of coronavirus disease 2019 (COVID-19), is transmitted person-to-person via respiratory droplets and, likely, via smaller droplet nuclei light enough to remain suspended in the air for hours and contaminate surfaces particularly in indoor conditions. Thus, effective measures are needed to prevent SARS-CoV-2 transmission in indoor environments. In this regard, we have investigated whether a system based on a filter combining Tungsten Trioxide-Based (WO3) photocatalysis and an antiviral fabric treated-copper nanocluster could inactivate SARS-CoV-2. To this purpose, an infectious SARS-CoV-2 suspension was introduced in the upper opening of a closed cylinder containing a WO3filter and a lightbased system that activates WO3and the antiviral fabric. From the bottom exit, aliquots of fluid were collected every 10 min (up to 60 min) and tested for their infectivity by means of a viral plaque assay in Vero cells whereas, in parallel, the viral RNA content was measured by quantitative PCR (qPCR). As we have previously shown for SARS-CoV, a 1:1,000 ratio of plaque forming units (PFU) vs. viral RNA copies was observed also for SARS-CoV-2. After 10 min, the infectious viral content was already decreased by 98.2% reaching 100% inactivation after 30 min whereas the SARS-CoV-2 RNA load was decreased of 1.5 log10after 30 min. Thus, in spite of only a partial decrease of viral RNA, SARS-CoV-2 infectivity was completely abolished by the WO3photocatalysis system by 30 min. These results support the hypothesis that this system could be exploited to achieve SARS-CoV-2 inactivation in indoor environments.
Multiple pools of Protein Phosphatase 2A-B56 function to antagonize spindle assembly, promote kinetochore attachments and maintain cohesion inDrosophilaOocytes
Authors: Jang Janet K. , Gladstein Amy C. , Das Arunika , Sisco Zachary L. , McKim Kim S. 
Published: August 2020

AbstractMeiosis in female oocytes lack centrosomes, the major microtubule-organizing center, which makes them especially vulnerable to aneuploidy. In the acentrosomal oocytes ofDrosophila, meiotic spindle assembly depends on the chromosomal passenger complex (CPC). Aurora B is the catalytic component of the CPC while the remaining subunits regulate its localization. Using an inhibitor of Aurora B activity, Binucleine 2, we found that continuous Aurora B activity is required to maintain the oocyte spindle during meiosis I, and this activity is antagonized by phosphatases acting on spindle associated proteins such as kinesins. Protein Phosphatase 2A (PP2A) exists in two varieties, B55 and B56. While both antagonize Aurora B, B55 has only minor roles in meiosis I spindle function. The B56 subunit is encoded by two partially redundant paralogs in theDrosophilagenome,wdbandwrd. Knocking down both paralogs showed that the B56 subunit is critical for maintaining sister chromatid cohesion, establishing end-on microtubule attachments, and the metaphase I arrest in oocytes. We found that WDB recruitment to the centromeres depends on BUBR1, MEI-S332, and kinetochore protein SPC105R. While BUBR1 has been shown previously to stabilize microtubule attachments inDrosophilaoocytes, only SPC105R is required for cohesion maintenance during meiosis I. We propose that SPC105R promotes cohesion maintenance by recruiting two proteins that recruit PP2A, MEI-S332, and the Soronin homolog Dalmatian.
A New Model of SARS-CoV-2 Infection Based on (Hydroxy) Chloroquine Activity
Authors: Sheaff Robert J. 
Published: August 2020

AbstractChloroquine and hydroxychloroquine (H)CQ are well known anti-malarial drugs, while their use against COVID-19 is more controversial. (H)CQ activity was examined in tissue culture cells to determine if their anti-viral benefits or adverse effects might be due to altering host cell pathways. Metabolic analysis revealed (H)CQ inhibit oxidative phosphorylation in mitochondria, likely by sequestering protons needed to drive ATP synthase. This activity could cause cardiotoxicity because heart muscle relies on beta oxidation of fatty acids. However, it might also explain their therapeutic benefit against COVID-19. A new model of SARS-CoV-2 infection postulates virus enters host cell mitochondria and uses its protons for genome release. Oxidative phosphorylation is eventually compromised, so glycolysis is upregulated to maintain ATP levels. (H)CQ could prevent viral infection and/or slow its replication by sequestering these protons. In support of this model other potential COVID-19 therapeutics also targeted mitochondria, as did tobacco smoke, which may underlie smokers’ protection. The mitochondria of young people are naturally more adaptable and resilient, providing a rationale for their resistance to disease progression. Conversely, obesity and diabetes could exacerbate disease severity by providing extra glucose to infected cells dependent on glycolysis. The description of (H)CQ function presented here, together with its implications for understanding SARS-CO-V2 infection, makes testable predictions about disease progression and identifies new approaches for treating COVID-19.
Integration of machine learning and genome-scale metabolic modeling identifies multi-omics biomarkers for radiation resistance
Authors: Lewis Joshua E. , Kemp Melissa L. 
Published: August 2020

AbstractResistance to ionizing radiation, a first-line therapy for many cancers, is a major clinical challenge. Personalized prediction of tumor radiosensitivity is not currently implemented clinically due to insufficient accuracy of existing machine learning classifiers. Despite the acknowledged role of tumor metabolism in radiation response, metabolomics data is rarely collected in large multi-omics initiatives such as The Cancer Genome Atlas (TCGA) and consequently omitted from algorithm development. In this study, we circumvent the paucity of personalized metabolomics information by characterizing 915 TCGA patient tumors with genome-scale metabolic Flux Balance Analysis models generated from transcriptomic and genomic datasets. Novel metabolic biomarkers differentiating radiation-sensitive and -resistant tumors were predicted and experimentally validated, enabling integration of metabolic features with other multi-omics datasets into ensemble-based machine learning classifiers for radiation response. These multi-omics classifiers showed improved classification accuracy, identified novel clinical patient subgroups, and demonstrated the utility of personalized blood-based metabolic biomarkers for radiation sensitivity. The integration of machine learning with genome-scale metabolic modeling represents a significant methodological advancement for identifying prognostic metabolite biomarkers and predicting radiosensitivity for individual patients.
Synaptic contributions to cochlear outer hair cell Ca2+homeostasis
Authors: Moglie Marcelo J. , Wengier Diego L. , Elgoyhen A. Belén , Goutman Juan D. 
Published: August 2020

AbstractFor normal cochlear function, outer hair cells (OHCs) require a precise regulation of intracellular Ca2+levels. Influx of Ca2+occurs both at the stereocillia tips and through the basolateral membrane. In this latter compartment, two different origins for Ca2+influx have been poorly explored: voltage-gated Ca2+channels (VGCC) at synapses with type II afferent neurons, and α9α10 cholinergic nicotinic receptors at synapses with medio-olivochlear complex (MOC) neurons. Using functional imaging in rodent OHCs, we report that these two Ca2+entry sites are closely positioned, but present different regulation mechanisms. Ca2+spread from MOC synapses is contained by cisternal Ca2+-ATPases. Considered a weak drive for transmitter release, we unexpectedly found that VGCC Ca2+signals are comparable in size to those elicited by α9α10 and can be potentiated by ryanodine receptors. Finally, we showed that sorcin, a highly expressed gene product in OHCs with reported Ca2+control function in cardiomy-ocytes, regulates basal Ca2+levels and MOC synaptic activity in OHCs.
HDAC1 regulates the chromatin landscape to establish transcriptional dependencies in chronic lymphocytic leukemia
Authors: Lai Tzung-Huei , Ozer Hatice Gulcin , Gasparini Pierluigi , Nigita Giovanni , Destefano Rosario , Yu Lianbo , Ravikrishnan Janani , Tsai Tzung-Lin , Lapalombella Rosa , Woyach Jennifer , Puduvalli Vinay , Blachly James , Byrd John C , Sampath Deepa 
Published: August 2020

AbstractHDAC1 is a key regulator of gene expression in cancer. We identified a critical role for HDAC1 in establishing the transcriptional dependencies essential for survival in chronic lymphocytic leukemia (CLL) by profiling HDAC1 with BRD4, H3K27Ac superenhancers, H4K9Ac, chromatin accessibility signatures, Pol2 measurements and expression signatures to generate a regulatory chromatin landscape. Superenhancers marked by high levels of acetylation and BRD4 paradoxically also recruited the highest levels of HDAC1. HDAC inhibition poisoned transcription at these loci to selectively disrupt B-cell transcription factors and B-cell receptor signaling. HDAC1 was also recruited genome-wide at promoters without superenhancers to repress expression; HDAC inhibition induces these genes which include key microRNA networks that reciprocally downregulate CLL specific survival and driver genes. Our work provides a compelling rationale for profiling HDAC1 across cancers to characterize its role in driving the transcriptional dysregulation that is a hallmark of most cancers and develop epigenetic therapeutic strategies.SignificanceOur work definitively establishes the composition of the regulatory chromatin that enables HDAC1 to function as an activator and repressor at distinct target genes within the same tumor to drive transcriptional dysregulation and allow the expression of B cell specific signaling and survival networks that are critical for survival.
Gender, women, and the future of tobacco control
Authors: Solomon Alexandra 
Published: August 2020

Purpose
This paper aims to provide a gendered analysis of the WHO Framework Convention on Tobacco Control (FCTC) benchmarked upon the global commitments to women’s health and well-being in the UN Convention on the Elimination of All Forms of Discrimination against Women (CEDAW) and the Beijing Declaration and Platform for Action. It reviews evidence of the global consequences of neglecting women’s tobacco use and health, as well as analyzes persistent issues related to sex and gender that compromise the efficacy of tobacco control and science. Actionable recommendations are made to the Conference of the Parties to the FCTC and other key stakeholders.

Design/methodology/approach
This paper draws upon empirical studies, literature reviews and global health data at the varying intersections of gender, sex, tobacco and global health.

Findings
The global tobacco control framework and its implementation by state governments have been largely gender blind to date with dire health and economic consequences, including inequitable positive outcomes for men compared to women, and an increase in women’s smoking with associated morbidity and mortality. Gender equitable progress in combatting the tobacco epidemic will not be possible without resolving the gender bias, stigmatization, sexism and lack of intersectionality that plague tobacco control policy, research and interventions for cessation and harm reduction.

Originality/value
This paper provides an updated global overview of current trends in women’s tobacco use and comprehensively details the persistent structural barriers in tobacco control and science that limit their capacity to effectively analyze and address tobacco use and its impact on women.
Discovery Digital Health strategy: COVID-19 accelerates online health care in South Africa
Authors: Moore Amy , Hawarden Verity 
Published: August 2020

Learning outcomes
The broad teaching objective is underpinned by the themes of purpose and partnerships. This is taught through application of business model innovation for sustainability where the value proposition is broadened to social and environmental, and multi-stakeholder partnerships in a time of crisis. Students will be expected to analyse the above concepts through a meso (sustainable value), micro (business models) and macro (ecosystems) lens. Upon completion of the case study discussion, successful students will be able to better understand the three features that support sustainable value, explore how a global pandemic can create new business models and partnerships to create social value and analyse how business ecosystems operate against the 6 C framework.

Case overview / synopsis
Discovery Holdings Limited is a leading financial service organisation in South Africa, and its Digital Health division is responsible for the platform which delivers telemedicine offerings to doctors and patients. The case highlights the development of the telemedicine offering and the period that is covered spans from the launch of the Discovery DrConnect platform in 2017 to April 2020. Adrian Moss is the protagonist in the case. He is a manager in the Special Projects, Digital Health team of Discovery Health, responsible for the DrConnect project. His challenge is how to raise more awareness of the DrConnect offering and how to enhance uptake from doctors and patients. COVID-19 and the lockdown in South Africa in March and April of 2020 presented an opportunity for both doctors and patients to use telemedicine as a new way of engagement and treatment.

Complexity academic level
This case is appropriate for masters, MBA and executive education students focusing on the fields of study of environment of business, strategy, business model innovation and social entrepreneurship.

Supplementary materials
Teaching Notes are available for educators only.

Subject code
CSS: 11 Strategy.
Innovative work behavior in SMEs: the role of transformational leadership
Authors: Knezović Emil , Drkić Amina 
Published: August 2020

PurposeThe purpose of this paper is to investigate the determinants of innovative work behavior (IWB) by examining the moderating role of transformational leadership in the context of small and medium enterprises (SMEs).Design/methodology/approachThe study surveyed 371 employees from SMEs in Bosnia and Herzegovina by adopting convenience sampling. Hierarchical regression was used to test the hypotheses.FindingsThe findings supported the authors’ assumptions that IWB determinants such as psychological empowerment, participation in the decision-making process and organizational justice are positively related to IWB. Besides, transformational leadership moderates the relationship between organizational justice and IWB.Research limitations/implicationsThe data for this study was collected by using convenience sampling as well as a cross-sectional survey method, which limits the generalization of results.Practical implicationsTo spur the IWB among the employees in SMEs, an organization has to create an environment where psychological empowerment is high, employees have a chance to participate in the decision-making process and organizational rules and procedures are fair. In the case of organizational justice, the relationship shall be stronger if transformational leadership is present.Originality/valueIn SMEs, transformational leadership plays an important role. To the best of the authors' knowledge, this is the first study that demonstrates the moderating effect of transformational leadership on the relationship between one specific IWB determinant and IWB.
“Poking around and reading the tea leaves”: analysis of issues affecting film and TV unions
Authors: Fuller Ryan P. , Michael Boniface 
Published: August 2020

PurposeThis research investigates the issues of concern for American film and television (TV) unions, the features of issues, whether issues are threats, opportunities or mixed evaluations, and unions' distributive or integrative approaches to issues (Walton and McKersie, 1965).Design/methodology/approachThe first author interviewed 25 union leaders and used thematic analysis to identify issue characteristics and evaluations of issues as threats, opportunities or mixed. Using language analysis, the authors then connected these evaluations to integrative or distributive approaches.FindingsThe findings revealed three larger issues of concern (positioning the union and jurisdiction, shifting patterns of risk and negotiating and enforcing contracts) and five characteristics (locus, boundary, manageability, predictability and scope). These characteristics then determined how interviewees viewed issues as threats, opportunities or mixed evaluations. Three characteristics grouped together to form threats: external locus, indistinct boundaries and low manageability. Indistinct boundaries contributed to assessments of issues as mixed. These issue types, characteristics and interpretations revealed a metaphorical above- and below-the-line differentiation among film and TV unions based on the members continued ownership of their work. With one exception – BTL unions on positioning union and jurisdiction – leaders' language reflected distributive approaches to issues.Originality/valueThis study delves deeper into Walton and McKersie's (1965) classical two-part classification of issues by adding a typology of characteristics and operational definitions to aid in identifying threats, opportunities and mixed evaluations through the novel use of issue analysis in industrial relations.