bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional expression of CXCL10 and STAT1 in lupus nephritis and the intervention effect of triptolide
Authors: Shi Dongliang , Li Yan , Shi Xiaomei , Yao Meihong , Wu Dan , Zheng Yuhui , Lin Qing , Yang Yinghong
Published: November 2022

Objective

This study screened out the key genes associated with the occurrence and development of lupus nephritis (LN) using bioinformatics methods, and then explored the expression of key genes in LN and the inhibitory effect of triptolide.

Methods

The GEO2R online tool in the GEO database was used to perform differential analysis of gene expression in LN tissues and normal kidney tissues. The GO function and KEGG pathway enrichment analysis of differentially expressed genes (DEGs), STRING, and Cytoscape software were used to build a protein–protein interaction network (PPI) to screen out the Hub gene. Mouse glomerular mesangial cells (MMC) were randomly divided into a control group, an interferon-γ (IFN-γ) stimulation group, and a triptolide intervention group. The relative expression of CXCL10 mRNA in each group was detected by real-time fluorescent quantitative PCR (RT-PCR). CXCL10 secretion was detected by enzyme-linked immunosorbent assay (ELISA), and Western blot was used to detect the expression of the JAK/STAT1 signaling pathway–related proteins STAT1 and p-STAT1 in each group.

Results

Bioinformatics showed that there were 22 DEGs expression differences in the GEO database. The GO enrichment analysis showed that biological process (BP) such as the type I interferon signaling pathway, innate immune response, IFN-γ-mediated signaling pathway, virus defense response, and immune response were significantly regulated by DEGs. Through the combination of String database analysis and cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN. Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway.

Conclusion

STAT1 and CXCL10 are the key genes in the occurrence and development of LN. IFN-γ induces the expression of CXCL10 by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 by blocking the JAK/STAT1 signaling pathway. Inhibition of the JAK/STAT1 signaling pathway and CXCL10 expression is expected to become a potential target for the treatment of LN.

Key Points• Bioinformatics showed that there were 22 DEGs expression differences in the GEO database.• Through the combination of String database analysis and Cytoscape software, it was found that STAT1 and CXCL10 are closely related to LN.• Experimental results showed that IFN-γ induces the expression of CXCL10 mRNA and protein by activating the JAK/STAT1 signaling pathway, while triptolide inhibits the expression of CXCL10 mRNA and protein by inhibiting the JAK/STAT1 signaling pathway.
Differentiation and Maturation of Muscle and Fat Cells in Cultivated Seafood: Lessons from Developmental Biology
Authors: Bomkamp Claire , Musgrove Lisa , Marques Diana M. C. , Fernando Gonçalo F. , Ferreira Frederico C. , Specht Elizabeth A.
Published: November 2022

Cultivated meat, also known as cultured or cell-based meat, is meat produced directly from cultured animal cells rather than from a whole animal. Cultivated meat and seafood have been proposed as a means of mitigating the substantial harms associated with current production methods, including damage to the environment, antibiotic resistance, food security challenges, poor animal welfare, and—in the case of seafood—overfishing and ecological damage associated with fishing and aquaculture. Because biomedical tissue engineering research, from which cultivated meat draws a great deal of inspiration, has thus far been conducted almost exclusively in mammals, cultivated seafood suffers from a lack of established protocols for producing complex tissues in vitro. At the same time, fish such as the zebrafish Danio rerio have been widely used as model organisms in developmental biology. Therefore, many of the mechanisms and signaling pathways involved in the formation of muscle, fat, and other relevant tissue are relatively well understood for this species. The same processes are understood to a lesser degree in aquatic invertebrates. This review discusses the differentiation and maturation of meat-relevant cell types in aquatic species and makes recommendations for future research aimed at recapitulating these processes to produce cultivated fish and shellfish.
Workplace Mental Health Disclosure, Sustainable Employability and Well-Being at Work: A Cross-Sectional Study Among Military Personnel with Mental Illness
Authors: Bogaers Rebecca , Geuze Elbert , van Weeghel Jaap , Leijten Fenna , van de Mheen Dike , Rüsch Nicolas , Rozema Andrea , Brouwers Evelien
Published: November 2022

Purpose Disclosure of mental illness to a supervisor can have positive (e.g. supervisor support) and negative consequences (e.g. stigma). However, research on the association between disclosure and sustainable employability and well-being at work is scarce. The aim of this study was to investigate the association between the disclosure decision (yes/no), experiences with the decision (positive/negative) and sustainable employment and well-being at work among military personnel with mental illness (N = 323). Methods A cross-sectional questionnaire study was conducted. Descriptive and regression (linear and ordinal) analyses were performed. Comparisons were made between those with positive and negative disclosure experiences. Results Disclosure decision (yes/no) was not significantly associated with any of the measures of sustainable employability and well-being at work. However, positive disclosure experiences were significantly associated with higher scores on almost all measures of sustainable employability and well-being at work. Those with negative disclosure experiences reported significantly more shame (Mpos = 2.42, Mneg = 2.78, p < .05) and discrimination (Mpos = 1.70, Mneg = 2.84, p < .001). Those with a positive disclosure experience, reported significantly more supervisor support (Mpos = 3.20, Mneg = 1.94, p < .001). Conclusion We did not find evidence that the disclosure decision itself is related to measures of sustainable employment and well-being at work. In contrast, how participants had experienced their (non-)disclosure decision was significantly related to almost all measures. This emphasizes the importance of the work environments reactions to disclosure and mental illness in the workplace. Future research and interventions should focus on increasing the likelihood of positive disclosure experiences through creating a more inclusive work environment, with more supervisor support and less stigma.
Evolution of Coronary Calcium Screening for Assessment of Atherosclerotic Cardiovascular Disease Risk and Role in Preventive Cardiology
Authors: Wong Nathan D.
Published: November 2022

Purpose of Review

Coronary artery calcium (CAC) is an important measure of subclinical atherosclerosis and strongly predicts atherosclerotic cardiovascular disease (ASCVD) outcomes. The purpose of this review is to discuss the key studies that have helped to establish its role as an important screening tool and its place in preventive cardiology.

Recent Findings

Epidemiologic studies document a strong relation of age, race/ethnicity, and risk factors with the prevalence and extent of CAC. Large-scale registry and prospective investigations show CAC to be the strongest subclinical disease predictor of ASCVD outcomes, with higher CAC scores associated with successively higher risks and those with a CAC score of 0 having a long-term “warranty” against having events. Moreover, CAC is associated with greater initiation of preventive health behaviors and therapy. Current US guidelines utilize CAC to inform the treatment decision for statin therapy. Further study is underway to document whether CAC screening will ultimately improve clinical outcomes.

CAC is well established as the most important subclinical cardiovascular disease measure for prediction of future ASCVD outcomes and can be used for informing the treatment decision for preventive therapies.
Value Change, Value Conflict, and Policy Innovation: Understanding the Opposition to the Market-Based Economic Dispatch of Electricity Scheme in India Using the Multiple Streams Framework
Authors: Goyal Nihit , Iychettira Kaveri
Published: November 2022

As policy innovation is essential for upscaling responsible innovation, understanding its relationship to value change(s) occurring or sought in sociotechnical systems is imperative. In this study, we ask: what are the different types of values in the policy process? And, how does value change influence policy innovation? We propose a disaggregation of values and value change based on a four-stream variant of the multiple streams framework (MSF), a conceptual lens increasingly used for explaining policy innovation in sociotechnical transitions. Specifically, we posit that the values that ‘govern’ problem framing, policy design, political decision making, and technological diffusion can evolve relatively independently, potentially leading to value conflict. We apply this framework to the ongoing case of the market-based economic dispatch of electricity (MBED) policy in the Indian energy transition using content analysis. We find that the MBED scheme—with its emphasis on efficiency (problem), economic principles (policy), low-cost dispatch (technology), and centralization (politics)—attempts value change in each stream. Each instance of value change is, however, widely contested, with the ensuing value conflicts resulting in significant opposition to this policy innovation. We conclude that a disaggregation of values based on the MSF can facilitate an analysis of value change and value conflict in sociotechnical transitions and lay the foundation for systematically studying the relationships among technological change, value change, and policy change.
The Ethics of Supernumerary Robotic Limbs. An Enactivist Approach
Authors: Di Stefano Nicola , Jarrassé Nathanaël , Valera Luca
Published: November 2022

Supernumerary robotic limbs are innovative devices in the field of wearable robotics which can provide humans with unprecedented sensorimotor abilities. However, scholars have raised awareness of the ethical issues that would arise from the large adoption of technologies for human augmentation in society. Most negative attitudes towards such technologies seem to rely on an allegedly clear distinction between therapy and enhancement in the use of technological devices. Based on such distinction, people tend to accept technologies when used for therapeutic purposes (e.g., prostheses), but tend to raise issues when similar devices are used for upgrading a physical or cognitive ability (e.g., supernumerary robotics limbs). However, as many scholars have pointed out, the distinction between therapy and enhancement might be theoretically flawed. In this paper, we present an alternative approach to the ethics of supernumerary limbs which is based on two related claims. First, we propose to conceive supernumerary limbs as tools that necessarily modify our psychological and bodily identity. At the same time, we stress that such a modification is not ethically bad in itself; on the contrary, it drives human interaction with the environment. Second, by comparing our view with the extended mind thesis, we claim that the mediation through tools is crucial for the formation of novel meanings and skills that constitute human interaction with the world. We will relate the latter claim to enactivism as a helpful theoretical perspective to frame issues related to artificial limbs and, more in general, to technologies for augmentation. Based on this approach, we finally sketch some suggestions for future directions in the ethics of supernumerary limbs.
Repentance as Rebuke: Betrayal and Moral Injury in Safety Engineering
Authors: Dekker Sidney W. A. , Layson Mark D. , Woods David D.
Published: November 2022

Following other contributions about the MAX accidents to this journal, this paper explores the role of betrayal and moral injury in safety engineering related to the U.S. federal regulator’s role in approving the Boeing 737MAX—a plane involved in two crashes that together killed 346 people. It discusses the tension between humility and hubris when engineers are faced with complex systems that create ambiguity, uncertain judgements, and equivocal test results from unstructured situations. It considers the relationship between moral injury, principled outrage and rebuke when the technology ends up involved in disasters. It examines the corporate backdrop against which calls for enhanced employee voice are typically made, and argues that when engineers need to rely on various protections and moral inducements to ‘speak up,’ then the ethical essence of engineering—skepticism, testing, checking, and questioning—has already failed.
Broadband optical frequency comb generation based on single electro-absorption modulation driven by radio frequency coupled signals
Authors: Jiang Pan , Li Peili , Fan Yiming
Published: November 2022

Broadband optical frequency comb (OFC) generation based on a single electro-absorption modulator (EAM) is proposed. The EAM is driven by a radio frequency (RF) multi-frequency signal generated by a multiplication coupler composed of an electrical power splitter and an arithmetic circuit. Thus the number of comb-lines of the generated OFC can be increased. A complete theoretical model of OFC generation by an EAM driven by nth power of the RF source is established, and the performance of the OFC is analyzed by using OptiSystem software. The results show that, the number of comb-lines of the OFC is positively correlated with the number of multiplication of the RF source signal. The frequency spacing of the comb-lines is twice the frequency of the RF source signal and is tunable by adjusting the frequency of the RF source signal. Increasing chirp factor and modulation index of EAM could increase the number of comb-lines of the generated OFC. The amplitude of the RF source signal had little impact on the flatness of the OFC and the average OFC power. The scheme developed is not only simple and low-cost, but also can produce a large number of comb-lines.

Graphical Abstract
Pointwise Expansion of Degenerating Immersions of Finite Total Curvature
Authors: Michelat Alexis , Rivière Tristan
Published: November 2022

Generalising classical result of Müller and Šverák (J. Differ. Geom. 42(2), 229-258, 1995), we obtain a pointwise estimate of the conformal factor of sequences of conformal immersions from the unit disk of the complex plane of uniformly bounded total curvature and converging strongly outside of a concentration point towards a branched immersions for which the quantization of energy holds. We show that the multiplicity associated to the conformal parameter becomes eventually constant to an integer equal to the order of the branch point of the limiting branched immersion. Furthermore, we deduce a$$C^0$$C0convergence of the normal unit in the neck regions. Finally, we show that these improved energy quantizations hold for Willmore surfaces of uniformly bounded energy and precompact conformal class, and for Willmore spheres arising as solutions of min-max problems in the viscosity method.
Astrocytes in Chronic Pain: Cellular and Molecular Mechanisms
Authors: Lu Huan-Jun , Gao Yong-Jing
Published: November 2022

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron–glia and glia–glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Historical biogeography highlights the role of Miocene landscape changes on the diversification of a clade of Amazonian tree frogs
Authors: Ortiz Diego A. , Hoskin Conrad J. , Werneck Fernanda P. , Réjaud Alexandre , Manzi Sophie , Ron Santiago R. , Fouquet Antoine
Published: November 2022

The diversification processes underlying why Amazonia hosts the most species-rich vertebrate fauna on earth remain poorly understood. We studied the spatio-temporal diversification of a tree frog clade distributed throughout Amazonia (Anura: Hylidae:Osteocephalus,Tepuihyla, andDryaderces) and tested the hypothesis that Miocene mega wetlands located in western and central Amazonia impacted connectivity among major biogeographic areas during extensive periods. We assessed the group’s diversity through DNA-based (16S rRNA) species delimitation to identify Operational Taxonomic Units (OTUs) from 557 individuals. We then selected one terminal for each OTU (n = 50) and assembled a mitogenomic matrix (~14,100 bp; complete for 17 terminals) to reconstruct a Bayesian, time-calibrated phylogeny encompassing nearly all described species. Ancestral area reconstruction indicates that each genus was restricted to one of the major Amazonian biogeographic areas (western Amazonia, Guiana Shield and Brazilian Shield, respectively) between ~10 and 20 Mya, suggesting that they diverged and diversified in isolation during this period around the Pebas mega wetland. After 10 Mya and the transition to the modern configuration of the Amazon River watershed, most speciation within each genus continued to occur within each area. InOsteocephalus, only three species expanded widely across Amazonia (< 6 Mya), and all were pond-breeders. Species with other breeding modes remained mostly restricted to narrow ranges. The spectacular radiation ofOsteocephaluswas probably driven by climatic stability, habitat diversity and the acquisition of new reproductive modes along the Andean foothills and western Amazonia. Our findings add evidence to the importance of major hydrological changes during the Miocene on biotic diversification in Amazonia.
Gewissheitsschwund: Über transformatives Führen in der ampeligen Lern-Koalition
Authors: Korte Karl-Rudolf
Published: November 2022

Führen und Entscheiden in Zeiten der Krisenpermanenz und dem damit einhergehenden Gewissheitsschwund wäre schon für erprobte Koalitionsformate eine große Herausforderung. Für die Ampel-Koalition sind diese ungleich größer. Die im vorliegenden Beitrag skizzierten vier Spielarten des transformativen Regierens deuten an, wie das Politikmanagement in der Transformation gelingen kann.
Vancomycin heteroresistance among methicillin-resistant clinical isolates S. haemolyticus, S. hominis, S. simulans, and S. warneri
Authors: Szemraj Magdalena , Lisiecki Paweł , Glajzner Paulina , Szewczyk Eligia M.
Published: November 2022

Besides being an essential part of the skin microbiome, coagulase-negative staphylococci are the etiological factors of serious infections. The aim of the study was to evaluate the heteroresistance to vancomycin and the potential antimicrobial efficacy of teicoplanin and daptomycin against the multiresistant strains of S. haemolyticus, S. hominis, S. warneri, and S. simulans. The study covered 80 clinical coagulase-negative staphylococci. Teicoplanin, vancomycin, and daptomycin MICs for the tested strains were determined according to EUCAST recommendation. The vanA and vanB genes were searched. The brain heart infusion screen agar method detected vancomycin heteroresistance. The population analysis profile method and analysis of autolytic activity were applied for the strains growing on BHI containing 4 mg/L vancomycin. Seven S. haemolyticus, two S. hominis, and two S. warneri strains presented a heterogeneous resistance to vancomycin. Their subpopulations were able to grow on a medium containing 4–12 mg/L of vancomycin. Monitoring heteroresistance to peptide antibiotics, which are often the last resort in staphylococcal infections, is essential due to the severe crisis in antibiotic therapy and the lack of alternatives to treat infections with multiresistant strains. Our work highlights the selection of resistant strains and the need for more careful use of peptide antibiotics.
Methionine addition improves the acid tolerance of Lactiplantibacillus plantarum by altering cellular metabolic flux, energy distribution, lipids composition
Authors: Meng Qiang , Li Yueyao , Yuan Yuxin , Wu Shaowen , Shi Kan , Liu Shuwen
Published: November 2022

This paper reported a wine-derived lactic acid bacterium, Lactiplantibacillus plantarum XJ25, which exhibited higher cell viability under acid stress upon methionine supplementation. Cellular morphology and the composition of the cytomembrane phospholipids revealed a more solid membrane architecture presented in the acid-stressed cells treated with methionine supplementation. Transcriptional analysis showed L. plantarum XJ25 reduced methionine transport and homocysteine biosynthesis under acid stress. Subsequent overexpression assays proved that methionine supplementation could alleviate the cell toxicity from homocysteine accumulation under acid stress. Finally, L. plantarum XJ25 employed energy allocation strategy to response environmental changes by balancing the uptake methionine and adjusting saturated fatty acids (SFAs) in membrane. These data support a novel mechanism of acid resistance involving methionine utilization and cellular energy distribution in LAB and provide crucial theoretical clues for the mechanisms of acid resistance in other bacteria.
Identity of AI
Authors: Devedzic Vladan
Published: November 2022

With the explosion of Artificial Intelligence (AI) as an area of study and practice, it has gradually become very difficult to mark its boundaries precisely and specify what exactly it encompasses. Many other areas of study are interwoven with AI, and new research and development topics that require interdisciplinary approach frequently attract attention. In addition, several AI subfields and topics are home to long-time controversies that give rise to seemingly never-ending debates that further obfuscate the entire area of AI and make its boundaries even more indistinct. To tackle such problems in a systematic way, this paper introduces the concept of identity of AI (viewed as an area of study) and discusses its dynamics, controversies, contradictions, and opposing opinions and approaches, coming from different sources and stakeholders. The concept of identity of AI emerges as a set of characteristics that shape up the current outlook on AI from epistemological, philosophical, ethical, technological, and social perspectives.
A 3D-induced pluripotent stem cell-derived human neural culture model to study certain molecular and biochemical aspects of Alzheimer’s disease
Authors: Prasannan Preeti , Siney Elodie , Chatterjee Shreyasi , Johnston David , Shah Mohammad , Mudher Amrit , Willaime-Morawek Sandrine
Published: November 2022

Purpose

Alzheimer’s disease (AD) early pathology needs better understanding and models. Here, we describe a human induced pluripotent stem cells (iPSCs)-derived 3D neural culture model to study certain aspects of AD biochemistry and pathology.

Method

iPSCs derived from controls and AD patients with Presenilin1 mutations were cultured in a 3D platform with a similar microenvironment to the brain, to differentiate into neurons and astrocytes and self-organise into 3D structures by 3 weeks of differentiation in vitro.

Results

Cells express astrocytic (GFAP), neuronal (β3-Tubulin, MAP2), glutamatergic (VGLUT1), GABAergic (GAD65/67), pre-synaptic (Synapsin1) markers and a low level of neural progenitor cell (Nestin) marker after 6 and 12 weeks of differentiation in 3D. The foetal 3R Tau isoforms and adult 4R Tau isoforms were detected at 6 weeks post differentiation, showing advanced neuronal maturity. In the 3D AD cells, total and insoluble Tau levels were higher than in 3D control cells.

Conclusion

Our data indicates that this model may recapitulate the early biochemical and pathological disease features and can be a relevant platform for studying early cellular and biochemical changes and the identification of drug targets.
Signal corrector and decoupling estimations for UAV control
Authors: Wang X.
Published: November 2022

For a class of uncertain systems with large-error sensing, the low-order stable signal corrector and observer are presented for signal correction and uncertainty estimation according to completely decoupling estimation. The model-free signal corrector can reject the bounded stochastic disturbance/error in global position sensing, and system uncertainty can be estimated by the observer, even the existence of large disturbance in position sensing. Furthermore, a general form of signal corrector is given. The describing function method is used to analyse the robustness of the corrector in frequency domain, and the parameter selection rules are presented. The merits of the signal corrector includes its model free, gain-bounded stable structure, sufficient rejection of bounded stochastic disturbance/error in sensing and ease of parameters’ regulation. The corrector and observer are applied to a UAV navigation and control for large disturbance/error corrections in position/attitude angle and the uncertainties estimation in the UAV flight dynamics. The control laws are designed according to the correction-estimation results. Finally, experiments demonstrate the effectiveness of the proposed method.
A framework for ‘configuring participation’ in living labs
Authors: Akasaka Fumiya , Mitake Yuya , Watanabe Kentaro , Shimomura Yoshiki
Published: November 2022

In recent years, ‘living lab (LL)’, a design approach that actively involves users as partners from the early stage of the design process, has been attracting much attention. Compared with the traditional participatory design or co-design approaches, one of the distinctive features of the LL approach is that the process of and opportunity for user participation tends to be long-term and complex. Thus, LL practitioners must appropriately plan and design effective integration of user participation into the design process to promote co-creation with users. In other words, LL practitioners are required to ‘configure user participation’ for the effective promotion of co-creation. However, to date, the knowledge on how to properly configure long-term and complex user participation in LLs has not been systematically clarified, nor have its methodologies been developed. This study develops a novel framework for configuring user participation in LLs. Through a literature review and analysis on LL case studies, we identified the 11 key elements in five categories that should be considered while configuring user participation in LLs. Furthermore, on the basis of the identified elements, we developed a novel framework for configuring user participation in LLs, which is called the participation blueprint. We have demonstrated its use and have also discussed its theoretical and practical contributions to the LL and co-design research community.
A comparative study of experiments with numerical simulations of free-stream turbulence transition
Authors: Mamidala Santhosh B. , Weingärtner André , Fransson Jens H.M.
Published: November 2022

To date, very few careful and direct comparisons between experiments and direct numerical simulations (DNS) have been published on free-stream turbulence (FST) induced boundary layer transition, whilst there exist numerous published works on the comparison of canonical turbulent boundary layers. The primary reason is that the former comparison is vastly more difficult to carry out simply because all known transition scenarios have large energy gradients and are extremely sensitive to surrounding conditions. This paper presents a detailed comparison between new experiments and available DNS data of the complex FST transition scenario in a flat plate boundary layer at turbulence intensity level about

$Tu = 3\,\%$

and FST Reynolds number about

$Re_{{fst}} = 67$

. The leading edge (LE) pressure gradient distribution and the full energy spectrum at the LE are identified as the two most important parameters for a satisfying comparison. Matching the LE characteristic FST parameters is not enough as previously thought, which is illustrated by setting up two experimental FST cases with about the same FST integral parameters at the LE but with different energy spectra. Finally, an FST boundary layer penetration depth (PD) measure is defined using DNS, which suggests that the PD grows with the downstream distance and stays around 20 % of the boundary layer thickness down to transition onset. With this result, one cannot rule out the significance of the continuous FST forcing along the boundary layer edge in this transition scenario, as indicated in previous studies.
Estimation of alcohol demand elasticity: Consumption of wine, beer, and spirits at home and away from home
Authors: Čiderová Tereza , Ščasný Milan
Published: November 2022

Most of the previous research examined the demand for alcohol consumed at the off-trade (consumed at home). However, some consumers might prefer to consume alcohol on-trade (away from home) or switch between on-trade and off-trade consumption as a reaction to price or income change. We estimate the Quadratic Almost Ideal Demand System consisting of three broad alcohol categories, consumed on-trade and off-trade, to derive own-price, cross-price, and income elasticities. Selectivity due to the high censoring is treated, and special attention is paid to quality-adjusted price. Beer consumption is the most responsive to income as well as own price changes, while spirits are the least responsive. The own-price elasticity of wine is –0.66 and –1.00 at on-trade and off-trade, respectively. Beer is more price responsive, spirits are less price responsive, and consumption reacts weaker in the off-trade market. Own-price elasticities of demand range between –1.20 and –0.41 at the off-trade and between –1.51 and –0.63 at the on-trade alcohol market. Increasing the price of wine in one market decreases wine consumption in another one. Between the two markets, wine and spirits are complementary, and wine and beer are substitutes in both markets.
The circadian rhythm regulates branched-chain amino acids metabolism in fast muscle of Chinese perch (Siniperca chuatsi) during short-term fasting by Clock-KLF15-Bcat2 pathway
Authors: Zhu Xin , Liu Jingjie , Cai Minglang , Bao Lingsheng , Pan Yaxiong , Wu Ping , Chu Wuying , Zhang Jianshe
Published: November 2022

As an internal time-keeping mechanism, circadian rhythm plays crucial role in maintaining homoeostasis when in response to nutrition change; meanwhile, branched-chain amino acids (BCAA) in skeletal muscle play an important role in preserving energy homoeostasis during fasting. Previous results from our laboratory suggested that fasting can influence peripheral circadian rhythm and BCAA metabolism in fish, but the relationship between circadian rhythm and BCAA metabolism, and whether circadian rhythm regulates BCAA metabolism to maintain physiological homoeostasis during fasting remains unclear. This study shows that the expression of fifteen core clock genes as well as KLF15 and Bcat2 is highly responsive to short-term fasting in fast muscle of Siniperca chuatsi, and the correlation coefficient between Clock and KLF15 expression is enhanced after fasting treatment. Furthermore, we demonstrate that the transcriptional expression of KLF15 is regulated by Clock, and the transcriptional expression of Bcat2 is regulated by KLF15 by using dual-luciferase reporter gene assay and Vivo-morpholinos-mediated gene knockdown technique. Therefore, fasting imposes a dynamic coordination of transcription between the circadian rhythm and BCAA metabolic pathways. The findings highlight the interaction between circadian rhythm and BCAA metabolism and suggest that fasting induces a switch in KLF15 expression through affecting the rhythmic expression of Clock, and then KLF15 promotes the transcription of Bcat2 to enhance the metabolism of BCAA, thus maintaining energy homoeostasis and providing energy for skeletal muscle as well as other tissues.
Locked in, logged out: pandemic and ride-hailing in South Africa and Kenya
Authors: Anwar Mohammad Amir , Otieno Elly , Stein Malte
Published: November 2022

This article examines the impact of the pandemic on ride-hailing drivers and their mitigation strategies during lockdown in Africa. Ride-hailing has emerged as one of the latest paid-work opportunities for the continent's many unemployed. Yet, ride-hailing companies such as Uber and Bolt misclassify drivers to avoid regulation and responsibilities towards workers’ welfare. Drawing on 34 in-depth interviews with ride-hailing drivers, driver representatives and trade unions in South Africa and Kenya, this article makes two arguments. First, the gig economy in Africa provides work opportunities for the unemployed on the continent and simultaneously vitiates the working conditions through the commodification and informalisation of work. Second, the state-directed emergency measures act as a veneer to capital's efforts to commodify labour and the gig economy platforms have emerged as primary tools for it. Our account points to an urgent need for better regulatory systems to hold platform companies accountable and a collective bargaining mechanism in the gig economy.
Companies in the Early Modern World: A Review of Recent Literature
Authors: Odegard Erik
Published: November 2022

Chartered companies provided one solution for the problems posed by long-distance trade in the early modern world. Accordingly, these organisations have been studied exhaustively. Yet the field is by no means depleted, as the books reviewed here attest. These six books cover questions ranging from whether the chartered companies acted as real business organisations or rather as appendages of state power, the relations between companies and states, the institutional development of the corporate form, and the nature of some of these companies as “company-states.” In addition, two edited volumes deal with specific aspects of the chartered companies and with noncorporate forms of merchant organisation. The works raise new questions and engage in ongoing debates. The review also raises a number of issues which could be addressed in future research, including the dominance of the East India Companies in our understanding of the corporate form as a whole.
The Welfare Diffusion Objection to Prioritarianism
Authors: Francis Tomi
Published: November 2022

According to the Welfare Diffusion Objection, we should reject Prioritarianism because it implies the ‘desirability of welfare diffusion’: the claim that it can be better for there to be less total wellbeing spread thinly between a larger total number of people, rather than for there to be more total wellbeing, spread more generously between a smaller total number of people. I argue that while Prioritarianism does not directly imply the desirability of welfare diffusion, Prioritarians are nevertheless implicitly committed to certain principles for comparing different-number populations which, together with the Prioritarian same-person axiology, imply the desirability of welfare diffusion.
Demolishing Modernism: GDR and Neo-Prussian Architecture in Berlin
Authors: Costa Xavier
Published: November 2022

This article examines the significance of some recent architecture and urban demolitions in Berlin. As an example of present-day iconoclasm in the heart of Europe, the relevance of these cases lies not only in the destruction of politically-charged artefacts, but also in their replacement with replicas of eighteenth-century architecture, thus materializing a Prussian revival and a nostalgia for the country’s royal past. In 2006, Berlin initiated the demolition of the Palace of the Republic (Palast der Republik). The Palast der Republik occupied the site of the original Berlin Palace, or Berliner Schloss, the residence of the Hohenzollern dynasty between 1701 and 1918. The demolition of the Palast has been followed by the construction of a replica of the eighteenth-century Schloss, but now intended to house the new Humboldt Forum, a museum dedicated to non-Western art. In recent years, both Berlin and neighbouring Potsdam have witnessed several integral reconstructions of historical buildings. This series of architecture demolitions and replicas therefore appears as a calculated and well-orchestrated operation to redefine the presence of the past through built artefacts, deserving to be examined from the broader perspective of iconoclastic precedents in art and architecture.
Applications of butyric acid in poultry production: the dynamics of gut health, performance, nutrient utilization, egg quality, and osteoporosis
Authors: El-Saadony Mohamed T. , Umar Muhammad , Hassan Faiz-ul , Alagawany Mahmoud , Arif Muhammad , Taha Ayman E. , Elnesr Shaaban S. , El-Tarabily Khaled A. , Abd El-Hack Mohamed E.
Published: November 2022

Due to the increasing demand for antibiotic-free livestock products from the consumer side and the ban on the use of antibiotic growth promoters, the poultry feed industry is increasingly interested in developing more alternatives to cope with this problem. Organic acids (butyric acid) have many beneficial effects on poultry health, performance, and egg quality when used in their diet, thus they can be considered for the replacement of antibiotics in livestock production systems. Butyric acid is most efficacious against pathogenic bacteria such as Salmonella spp. and Escherichia coli, and stimulates the population of beneficial gut bacteria. It is a primary energy source for colonocytes and augments the differentiation and maturation of the intestinal cells. Collectively, butyric acid should be considered as an alternative to antibiotic growth promoters, because it reduces pathogenic bacteria and their toxins, enhancing gut health thereby increasing nutrient digestibility, thus leading to improved growth performance and immunity among birds. The possible pathways and mechanisms through which butyric acid enhances gut health and production performance are discussed in this review. Detailed information about the use of butyric acid in poultry and its possible benefits under different conditions are also provided, and the impacts of butyric acid on egg quality and osteoporosis are noted.
Auxiliary Selection in Yiddish Dialects
Authors: Schäfer Lea
Published: November 2022

The variation of the two past tense auxiliaries (HAVE and BE) is a well-studied phenomenon in European languages, especially in the West Germanic varieties. So far, however, the situation in Eastern Yiddish has not been examined. This paper focuses on auxiliary selection in these Yiddish dialects based on data from the Language and Culture Archive of Ashkenazic Jewry, which were collected in the 1960s. Like most of the current works on this topic, the following analysis uses and discusses Sorace’s (1993, 2000) Auxiliary Selection Hierarchy, which allows to examine the Yiddish structures in light of historical and diatopic evidence from other Germanic varieties, particularly German and Dutch. The main focus is on intransitive verbs that show a high degree of variation—state verbs, controlled and uncontrolled motional process verbs, and change-of-state verbs. However, the Auxiliary Selection Hierarchy also has weaknesses, as is demonstrated in the following.*
On the Predictability of the Extreme Drought in East Africa During the Short Rains Season
Authors: Doi Takeshi , Behera Swadhin K. , Yamagata Toshio
Published: November 2022

Many parts of East Africa experienced extremely dry conditions during the short rains season of October–December 2021. It was predicted a few months before by the ensemble seasonal prediction system based on the SINTEX‐F climate model. The analysis of co‐variability of inter‐member anomalies has revealed that the 2021 negative Indian Ocean Dipole was responsible for these unusually dry conditions over East Africa. We also show that a hybrid statistical‐dynamical framework is more skillful than the SINTEX‐F model at predicting drought in East Africa on longer lead time, which may help people to take necessary mitigation measures to reduce the devastating impact of the drought.
VIP152 is a selective CDK9 inhibitor with pre-clinical in vitro and in vivo efficacy in chronic lymphocytic leukemia
Authors: Sher Steven , Whipp Ethan , Walker Janek , Zhang Pu , Beaver Larry , Williams Katie , Orwick Shelley , Ravikrishnan Janani , Walker Brandi , Perry Elizabeth , Gregory Charles , Purcell Matthew , Pan Alexander , Yan Pearlly , Alinari Lapo , Johnson Amy J. , Frigault Melanie M. , Greer Joy M. , Hamdy Ahmed , Izumi Raquel , Mo Xiaokui , Sampath Deepa , Woyach Jennifer , Blachly James , Byrd John C. , Lapalombella Rosa
Published: November 2022

Chronic lymphocytic leukemia (CLL) is effectively treated with targeted therapies including Bruton tyrosine kinase inhibitors and BCL2 antagonists. When these become ineffective, treatment options are limited. Positive transcription elongation factor complex (P-TEFb), a heterodimeric protein complex composed of cyclin dependent kinase 9 (CDK9) and cyclin T1, functions to regulate short half-life transcripts by phosphorylation of RNA Polymerase II (POLII). These transcripts are frequently dysregulated in hematologic malignancies; however, therapies targeting inhibition of P-TEFb have not yet achieved approval for cancer treatment. VIP152 kinome profiling revealed CDK9 as the main enzyme inhibited at 100 nM, with over a 10-fold increase in potency compared with other inhibitors currently in development for this target. VIP152 induced cell death in CLL cell lines and primary patient samples. Transcriptome analysis revealed inhibition of RNA degradation through the AU-Rich Element (ARE) dysregulation. Mechanistically, VIP152 inhibits the assembly of P-TEFb onto the transcription machinery and disturbs binding partners. Finally, immune competent mice engrafted with CLL-like cells of Eµ-MTCP1 over-expressing mice and treated with VIP152 demonstrated reduced disease burden and improvement in overall survival compared to vehicle-treated mice. These data suggest that VIP152 is a highly selective inhibitor of CDK9 that represents an attractive new therapy for CLL.
Altered purinergic receptor expression in the frontal cortex in schizophrenia
Authors: Alnafisah Rawan , Lundh Anna , Asah Sophie M. , Hoeflinger Julie , Wolfinger Alyssa , Hamoud Abdul-rizaq , McCullumsmith Robert E. , O’Donovan Sinead M.
Published: November 2022

ATP functions as a neurotransmitter, acting on the ubiquitously expressed family of purinergic P2 receptors. In schizophrenia (SCZ), the pathways that modulate extracellular ATP and its catabolism to adenosine are dysregulated. However, the effects of altered ATP availability on P2 receptor expression in the brain in SCZ have not been assessed. We assayed P2 receptor mRNA and protein expression in the DLPFC and ACC in subjects diagnosed with SCZ and matched, non-psychiatrically ill controls (n = 20–22/group). P2RX7, P2RX4 and male P2RX5 mRNA expression were significantly increased (p < 0.05) in the DLPFC in SCZ. Expression of P2RX7 protein isoform was also significantly increased (p < 0.05) in the DLPFC in SCZ. Significant increases in P2RX4 and male P2RX5 mRNA expression may be associated with antipsychotic medication effects. We found that P2RX4 and P2RX7 mRNA are significantly correlated with the inflammatory marker SERPINA3, and may suggest an association between upregulated P2XR and neuroinflammation in SCZ. These findings lend support for brain-region dependent dysregulation of the purinergic system in SCZ.
Epigenetic silencing by the SMC5/6 complex mediates HIV-1 latency
Authors: Irwan Ishak D. , Bogerd Hal P. , Cullen Bryan R.
Published: November 2022

After viral entry and reverse transcription, HIV-1 proviruses that fail to integrate are epigenetically silenced, but the underlying mechanism has remained unclear. Using a genome-wide CRISPR/Cas9 knockout screen, we identified the host SMC5/6 complex as essential for this epigenetic silencing. We show that SMC5/6 binds to and then SUMOylates unintegrated chromatinized HIV-1 DNA. Inhibition of SUMOylation, either by point mutagenesis of the SMC5/6 component NSMCE2—a SUMO E3 ligase—or using the SUMOylation inhibitor TAK-981, prevents epigenetic silencing, enables transcription from unintegrated HIV-1 DNA and rescues the replication of integrase-deficient HIV-1. Finally, we show that blocking SMC5/6 complex expression, or inhibiting its SUMOylation activity, suppresses the establishment of latent HIV-1 infections in both CD4+ T cell lines and primary human T cells. Collectively, our data show that the SMC5/6 complex plays a direct role in mediating the establishment of HIV-1 latency by epigenetically silencing integration-competent HIV-1 proviruses before integration.
Enabling FAIR data in Earth and environmental science with community-centric (meta)data reporting formats
Authors: Crystal-Ornelas Robert , Varadharajan Charuleka , O’Ryan Dylan , Beilsmith Kathleen , Bond-Lamberty Benjamin , Boye Kristin , Burrus Madison , Cholia Shreyas , Christianson Danielle S. , Crow Michael , Damerow Joan , Ely Kim S. , Goldman Amy E. , Heinz Susan L. , Hendrix Valerie C. , Kakalia Zarine , Mathes Kayla , O’Brien Fianna , Pennington Stephanie C. , Robles Emily , Rogers Alistair , Simmonds Maegen , Velliquette Terri , Weisenhorn Pamela , Welch Jessica Nicole , Whitenack Karen , Agarwal Deborah A.
Published: November 2022

Research can be more transparent and collaborative by using Findable, Accessible, Interoperable, and Reusable (FAIR) principles to publish Earth and environmental science data. Reporting formats—instructions, templates, and tools for consistently formatting data within a discipline—can help make data more accessible and reusable. However, the immense diversity of data types across Earth science disciplines makes development and adoption challenging. Here, we describe 11 community reporting formats for a diverse set of Earth science (meta)data including cross-domain metadata (dataset metadata, location metadata, sample metadata), file-formatting guidelines (file-level metadata, CSV files, terrestrial model data archiving), and domain-specific reporting formats for some biological, geochemical, and hydrological data (amplicon abundance tables, leaf-level gas exchange, soil respiration, water and sediment chemistry, sensor-based hydrologic measurements). More broadly, we provide guidelines that communities can use to create new (meta)data formats that integrate with their scientific workflows. Such reporting formats have the potential to accelerate scientific discovery and predictions by making it easier for data contributors to provide (meta)data that are more interoperable and reusable.
Effect of metal oxides on the light radiation intensity of Ba(NO3)2/Mg-containing pyrotechnic mixtures combustion
Authors: Ouyang Di-hua , Yang Chun-hai , Zhang Qian-tao , Yan Hao-yu , Pang Wei-qiang
Published: November 2022

Studying how to improve the performance of illuminating agents to meet the requirements of ammunition miniaturization of great importance. In this study, a simple method for increasing light radiation intensity through the adding of metal oxides was developed and tested. Results revealed that the metal oxides had a very strong effect on the light radiation intensity of the reaction system. Optical radiation intensity increased by 17.8%, − 5.4% and 25.9% after the addition 5% of MgO, Al2O3and BaO to the Ba(NO3)2/Mg reaction system, respectively. This phenomenon may be related to the light radiation characteristics and reactivity of the metal oxide itself, as well as the temperature at which the added metal oxide can be excited to radiate light intensity.