bluuebunny/crossref_metadata_2025 huggingface dataset:
Running a Consultancy
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter outlines the challenges involved in running a consultancy, particularly the concept of leverage and the strategic options for different types of consultancy. It describes the unique characteristics of people management in consulting firms and highlights the difference between types of knowledge management in consulting firms. It also discusses the operational challenges of consultancy, focusing on innovation, growth, and internationalization. The chapter analyses the finances of professional service firms, which are a complex but essential area to understand if long term stability is to be achieved in a firm. It looks at people management and resourcing strategies that are important in consultancy practice and must be aligned with the firm's financial and marketing strategies.
Critical Themes in Consulting
Authors: O’Mahoney Joe , Markham Calvert
Published: September 2023

This chapter provides an overview of critical themes that give a deeper understanding and analysis of consultancy as a political and sociological phenomenon. It explains the history and importance of critical thinking and the role of consultants in developing the knowledge economy. It also assesses the extent to which consultants can be described as innovators and describes the professionalization of the consulting industry. The chapter explores the relationship between consultancy and the risks inherent in modern capitalism, including approaches academics have taken to explaining consulting identities. It considers consultancy as a contributor to the spread of neo-liberal forms of capitalism.
Marketing Research
Authors: Bradley Nigel
Published: September 2023

Marketing Research consists of four parts. Part 1 looks at research preparation. Part 2 is about data collection. It examines secondary data, primary data, sampling, questionnaires, qualitative research, and quantitative research. Part 3 is about analysis and communication. Part 4 looks at the marketing research context which includes business-to-business research, international research, audience and advertising research, and web metrics.
Planning research
Authors: Bradley Nigel
Published: September 2023

This chapter considers the complex area of planning research studies. It introduces a framework called ‘the marketing research mix’. This new ‘mix’ defines the sequence of research. It provides the purpose, population, procedure, and publication stages of any project. In practical terms, research plans are agreed between a client and supplier using two documents: the brief and the proposal. The chapter demonstrates how to prepare both documents and informs what is good practice.
Primary data
Authors: Bradley Nigel
Published: September 2023

This chapter discusses data collected from the field which has to happen to satisfy specific research needs. The channels used vary from face-to-face and telephone to postal delivery services and online. The chapter evaluates different methods used to collect data and the problems posed when dealing with the measurement of human activities. Data capture may mean asking respondents to complete tasks themselves or it may involve the use of skilled interviewers. Interviewing skills are extremely important to achieve the best possible cooperation.
Questionnaires and topic guides
Authors: Bradley Nigel
Published: September 2023

This chapter delves into the design of a structured questionnaire, an important tool in quantitative research. It provides help on designing a questionnaire that is ‘fit for purpose’. It introduces the concept of open and closed questions, projective techniques, and scales. For qualitative researchers, the ‘topic guide’ is important and again guidance is given. The chapter concludes with an account of questionnaire variants: the diary and the observation form.
Reporting and presentation
Authors: Bradley Nigel
Published: September 2023

This chapter features the skills involved in communicating findings, reporting, and presentation. The final part of the research depends on the ways by which information can be delivered to the right people. The chapter presents an explanation of different visual displays of data. It also considers what is expected from writers of research reports. It emphasizes the importance of using a style that is appropriate to the situation. Finally, it examines how the internet has been used to communicate the results produced by market researchers in recent years, becoming a new channel for information.
Audience and advertising research
Authors: Bradley Nigel
Published: September 2023

This chapter discusses audience and advertising research. It provides the purposes and shows the importance of audience and advertising research. Media measurement surveys dictate the amounts paid to buy advertising space; they also offer ready-made segmentation to marketing managers. Audience research offers guidance for media owners on what is of interest to readers, viewers, or listeners. The chapter addresses newspapers, magazines, radio, television, the internet, outdoor, and cinema. It also looks at how research can provide some indication of advertising effectiveness. Various measures are enumerated, including impact, emotional involvement, brand recall, image, comprehension, reactions, associations, recognition, appeal, and persuasiveness. The chapter concludes with what must be considered in the publication stage of the research.
Web metrics
Authors: Bradley Nigel
Published: September 2023

This chapter looks at web metrics. It incorporates the two topics of web analytics and social media monitoring. It begins with an introduction of the topics and distinguishes between the two approaches. It also examines their purpose, population, procedure, and some aspects related to publication. It also provides practical help in using some of the principles of web metrics, whether it is to enrich academic projects or application to active companies and brands.
Understanding employability and your development needs
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter looks into case studies to illustrate the concept of employability. It quotes Mantz Yorke to define employability as a set of achievements that makes a graduate more likely to gain employment. The chapter argues that employers tend to recruit people with strong self-efficacy while referencing the key elements of the ‘CareerEDGE’ model of employability: reflection and evaluation. It also regards IT literacy skills as vital. It includes punctuality and discipline as important attributes. Next, the chapter lists the top eight mindset qualities such as honesty and trustworthiness. It asks readers to reflect on themselves, working with others, and evidence of graduate assets.
Employability audit, learning logs and portfolio-building
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter focuses on understanding and improving employability assets. It explains the principles of Personal Development Planning (PDP): concrete experience, reflective observation, abstract conceptualization, and active experimentation. Then, it highlights the importance of mindset. The chapter argues the case for creating an employability development questionnaire and learning log formats in relation to identifying the level of confidence in employability assets. It references the CareerEDGE model of employability and Kolb's Learning Cycle as the basis for assessing employability. The chapter encourages readers to have planned strategies and actions to tackle areas of improvement to gather evidence of employability assets for their portfolios. Finally, it looks into thinking through career options as well.
Teamwork 2: Maintenance
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter explores group dynamics. It looks into problem-solving strategies such as team evaluation, effort acknowledgment, and communication. The chapter delves into working in culturally diverse teams by showing that culturally-different team members will have different behaviours and communication methods. It identifies relationship, power, and uncertainty as challenges to the team dynamic. The chapter gives tips on how to amicably solve team problems through communication, negotiation, and mediation. It points out the significance of understanding unspoken messages in an effort to deal sensitively with colleagues. The chapter concludes with Carl Rogers' suggestion in establishing a good and trusting relationship through unconditional positive regard, empathy, and congruence.
Finding a job
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter discusses the process of finding a job. It explains the range of places wherein a person could find jobs such as newspapers, online job boards, or graduate fairs. The chapter highlights the importance of researching the company and company requirements prior to the job interview. It explains the preparation for possible interviews such as face-to-face, telephone, or online. The chapter adds the significance of confidence, preparation, and practice amidst the interview process. It mentions how being shortlisted for a job will be the culmination of hard work. The chapter notes that self-awareness developed through Personal Development Planning will help the candidate understand what kind of organization they are best suited for.
Into work: succeeding in the workplace
Authors: Lumley Maryvonne , Wilkinson James
Published: September 2023

This chapter looks into succeeding in the workplace. It highlights the significance of building experience, making good first impressions, and clarifying questions. The chapter discusses how to make a good impression such as being punctual, dressing smartly, showing enthusiasm, and paying attention. It shows how first days in the workplace might proceed by giving tips on being attentive on ground rules, group ethos, work-life balance, and attendance. Meanwhile, the chapter gives tips on observing intrapreneurship and ethics. It suggests working smart instead of only working harder. The chapter also shares the experience of two new starting workers and an experienced employer to emphasize each point's importance.
From lipid nanoparticles to precision therapies for hematologic diseases: getting closer
Authors: Mayani Hector
Published: September 2023

Modification of hematopoietic stem cells, in both molecular and cellular terms, has been a long-pursued goal in experimental and clinical hematology. In a recent article published in Science, Breda et al describe a novel method for the genetic modification of hematopoietic stem cells. This new experimental approach, based on the use of lipid nanoparticles, represents an important step forward in the development of genetic and cellular therapies for hematologic diseases. A general overview of the article by Breda et al and some analysis, comments, and perspectives are presented in this editorial commentary.
The National Cancer Institute’s Cancer Disparities Research Partnership Program: a unique funding model 20 years later
Authors: Coleman C Norman , Wong Rosemary , Petereit Daniel G , Maguire Patrick D , Heron Dwight E , Steinberg Michael , Bains Yadvindera , Vikram Bhadrasain , Angelis Patricia , Livinski Alicia A , Roach Mack , Govern Frank S
Published: September 2023

The burden of cancer and access to effective treatment are not experienced equally by all in the United States. For underserved populations that often access the health-care system when their cancers are in advanced disease stages, radiation oncology services are essential. In 2001, the National Cancer Institute’s (NCI’s) Radiation Research Program created and implemented the Cancer Disparities Research Partnership Program (CDRP). CDRP was a pioneering funding model whose goal was to increase participation of medically underserved populations in NCI clinical trials. CDRP’s Cooperative Agreement funding supported for awardees the planning, development, and conduct of radiation oncology clinical research in institutions not traditionally involved in NCI-sponsored research and cared for a disproportionate number of medically underserved, health-disparities populations. The awardee secured and provided support for mentorship from 1 of 2 NCI comprehensive cancer centers named in its application. Six CDRP awards were made over two 5-year funding periods ending in 2013, with the end-of-program accomplishments previously reported. With the current focus on addressing equity, diversity, and inclusion, the 6 principal investigators were surveyed, 5 of whom responded about the impact of CDRP on their institutions, communities, and personal career paths. The survey that was emailed included 10 questions on a 5-point Likert scale. It was not possible to collect patient data this long after completion of the program. This article provides a 20-year retrospective of the experiences and observations from those principal investigators that can inform those now planning, building, and implementing equity, diversity, and inclusion programs.
Is the co-option of jasmonate signalling for botanical carnivory a universal trait for all carnivorous plants?
Authors: Pavlovič Andrej , Koller Jana , Vrobel Ondřej , Chamrád Ivo , Lenobel René , Tarkowski Petr
Published: September 2023

The carnivorous plants in the order Caryophyllales co-opted jasmonate signalling from plant defence to botanical carnivory. However, carnivorous plants have at least 11 independent origins, and here we ask whether jasmonate signalling has been co-opted repeatedly in different evolutionary lineages. We experimentally wounded and fed the carnivorous plants Sarracenia purpurea (order Ericales), Cephalotus follicularis (order Oxalidales), Drosophyllum lusitanicum (order Caryophyllales), and measured electrical signals, phytohormone tissue level, and digestive enzymes activity. Coronatine was added exogenously to confirm the role of jasmonates in the induction of digestive process. Immunodetection of aspartic protease and proteomic analysis of digestive fluid was also performed. We found that prey capture induced accumulation of endogenous jasmonates only in D. lusitanicum, in accordance with increased enzyme activity after insect prey or coronatine application. In C. follicularis, the enzyme activity was constitutive while in S. purpurea was regulated by multiple factors. Several classes of digestive enzymes were identified in the digestive fluid of D. lusitanicum. Although carnivorous plants from different evolutionary lineages use the same digestive enzymes, the mechanism of their regulation differs. All investigated genera use jasmonates for their ancient role, defence, but jasmonate signalling has been co-opted for botanical carnivory only in some of them.
A striking relationship between dust extinction and radio detection in DESI QSOs: evidence for a dusty blow-out phase in red QSOs
Authors: Fawcett V A , Alexander D M , Brodzeller A , Edge A C , Rosario D J , Myers A D , Aguilar J , Ahlen S , Alfarsy R , Brooks D , Canning R , Circosta C , Dawson K , de la Macorra A , Doel P , Fanning K , Font-Ribera A , Forero-Romero J E , Gontcho A Gontcho S , Guy J , Harrison C M , Honscheid K , Juneau S , Kehoe R , Kisner T , Kremin A , Landriau M , Manera M , Meisner A M , Miquel R , Moustakas J , Nie J , Percival W J , Poppett C , Pucha R , Rossi G , Schlegel D , Siudek M , Tarlé G , Weaver B A , Zhou Z , Zou H
Published: September 2023

We present the first eight months of data from our secondary target programme within the ongoing Dark Energy Spectroscopic Instrument (DESI) survey. Our programme uses a mid-infrared and optical colour selection to preferentially target dust-reddened quasi-stellar objects (QSOs) that would have otherwise been missed by the nominal DESI QSO selection. So far, we have obtained optical spectra for 3038 candidates, of which ∼70 per cent of the high-quality objects (those with robust redshifts) are visually confirmed to be Type 1 QSOs, consistent with the expected fraction from the main DESI QSO survey. By fitting a dust-reddened blue QSO composite to the QSO spectra, we find they are well-fitted by a normal QSO with up to AV ∼ 4 mag of line-of-sight dust extinction. Utilizing radio data from the LOFAR Two-metre Sky Survey (LoTSS) DR2, we identify a striking positive relationship between the amount of line-of-sight dust extinction towards a QSO and the radio detection fraction, that is not driven by radio-loud systems, redshift and/or luminosity effects. This demonstrates an intrinsic connection between dust reddening and the production of radio emission in QSOs, whereby the radio emission is most likely due to low-powered jets or winds/outflows causing shocks in a dusty environment. On the basis of this evidence, we suggest that red QSOs may represent a transitional ‘blow-out’ phase in the evolution of QSOs, where winds and outflows evacuate the dust and gas to reveal an unobscured blue QSO.
ATMOSPHERIX: II- Characterizing exoplanet atmospheres through transmission spectroscopy with SPIRou
Authors: Debras Florian , Klein Baptiste , Donati Jean-François , Hood Thea , Moutou Claire , Carmona Andres , Charnay Benjamin , Bézard Bruno , Fouqué Pascal , Masson Adrien , Vinatier Sandrine , Baruteau Clément , Boisse Isabelle , Bonfils Xavier , Chiavassa Andrea , Delfosse Xavier , Hebrard Guillaume , Leconte Jérémy , Martioli Eder , Ould-elkhim Merwan , Parmentier Vivien , Petit Pascal , Pluriel William , Selsis Franck , Teinturier Lucas , Tremblin Pascal , Turbet Martin , Venot Olivia , Wyttenbach Aurélien
Published: September 2023

In a companion paper, we introduced a publicly available pipeline to characterize exoplanet atmospheres through high-resolution spectroscopy. In this paper, we use this pipeline to study the biases and degeneracies that arise in atmospheric characterization of exoplanets in near-infrared ground-based transmission spectroscopy. We inject synthetic planetary transits into sequences of SPIRou spectra of the well known M dwarf star Gl 15 A, and study the effects of different assumptions on the retrieval. We focus on (i) mass and radius uncertainties, (ii) non-isothermal vertical profiles, and (iii) identification and retrieval of multiple species. We show that the uncertainties on mass and radius should be accounted for in retrievals and that depth-dependent temperature information can be derived from high-resolution transmission spectroscopy data. Finally, we discuss the impact of selecting wavelength orders in the retrieval and the issues that arise when trying to identify a single species in a multispecies atmospheric model. This analysis allows us to understand better the results obtained through transmission spectroscopy and their limitations in preparation to the analysis of actual SPIRou data.
Detection, instance segmentation, and classification for astronomical surveys with deep learning (deepdisc): detectron2 implementation and demonstration with Hyper Suprime-Cam data
Authors: Merz Grant , Liu Yichen , Burke Colin J , Aleo Patrick D , Liu Xin , Carrasco Kind Matias , Kindratenko Volodymyr , Liu Yufeng
Published: September 2023

The next generation of wide-field deep astronomical surveys will deliver unprecedented amounts of images through the 2020s and beyond. As both the sensitivity and depth of observations increase, more blended sources will be detected. This reality can lead to measurement biases that contaminate key astronomical inferences. We implement new deep learning models available through Facebook AI Research’s detectron2 repository to perform the simultaneous tasks of object identification, deblending, and classification on large multiband co-adds from the Hyper Suprime-Cam (HSC). We use existing detection/deblending codes and classification methods to train a suite of deep neural networks, including state-of-the-art transformers. Once trained, we find that transformers outperform traditional convolutional neural networks and are more robust to different contrast scalings. Transformers are able to detect and deblend objects closely matching the ground truth, achieving a median bounding box Intersection over Union of 0.99. Using high-quality class labels from the Hubble Space Telescope, we find that when classifying objects as either stars or galaxies, the best-performing networks can classify galaxies with near 100 per cent completeness and purity across the whole test sample and classify stars above 60 per cent completeness and 80 per cent purity out to HSC i-band magnitudes of 25 mag. This framework can be extended to other upcoming deep surveys such as the Legacy Survey of Space and Time and those with the Roman Space Telescope to enable fast source detection and measurement. Our code, deepdisc, is publicly available at https://github.com/grantmerz/deepdisc.
Why should models of dwarf galaxy evolution care about the initial mass function at low star-formation rates?
Authors: Steyrleithner P , Hensler G
Published: September 2023

When star clusters are formed at low star-formation rates (SFRs), their stellar initial mass function (IMF) can hardly be filled continuously with stars at each mass. This lack holds for massive stars and is verified observationally by the correlation between star-cluster mass and its most massive cluster star. Since galaxy evolution is strongly affected by massive stars, numerical models should account for this lack. Because a filled IMF is mostly applied even when only fractions of massive stars form, here we investigate, by means of 3D chemo-dynamical simulations of isolated dwarf galaxies, how deviations from a standard IMF in star clusters affect the evolution. We compare two different IMF recipes, a filled IMF and one truncated at a maximum mass at which a single complete star forms. Attention is given to energetic and chemical feedback by massive stars. Since their energy release is mass-dependent but steeper than the negative IMF slope, the energetic feedback retains a positive mass dependence, so that a filled IMF regulates star formation (SF) more strongly than truncated IMFs, though only stellar number fractions exist. The higher SFR of the truncated IMF in the simulation leads to more Type II supernovae (SNeII), driving galactic winds. Whether this results from the model-inherent larger SFR is questioned and therefore explored analytically. This shows the expected result for the Lyman continuum, but that the total SNII energy release is equal for both IMF modes, while the power is smaller for the truncated IMF. Reasonably, the different IMFs leave fingerprints in the abundance ratios of massive to intermediate-mass star elements.
The kinematic structure of magnetically aligned H i filaments
Authors: Kim Doyeon A , Clark S E , Putman M E , Li Larry
Published: September 2023

We characterize the kinematic and magnetic properties of H i filaments located in a high Galactic latitude region (165° < α < 195° and 12° < δ < 24°). We extract three-dimensional filamentary structures using fil3d from the Galactic Arecibo L-Band Feed Array H i (GALFA-H i) survey 21-cm emission data. Our algorithm identifies coherent emission structures in neighbouring velocity channels. Based on the mean velocity, we identify a population of local and intermediate velocity cloud (IVC) filaments. We find the orientations of the local (but not the IVC) H i filaments are aligned with the magnetic field orientations inferred from Planck 353 GHz polarized dust emission. We analyse position–velocity diagrams of the velocity-coherent filaments, and find that only 15 per cent of filaments demonstrate significant major-axis velocity gradients with a median magnitude of 0.5 km s−1 pc−1, assuming a fiducial filament distance of 100 pc. We conclude that the typical diffuse H i filament does not exhibit a simple velocity gradient. The reported filament properties constrain future theoretical models of filament formation.
A global turbulence model shows excellent atmospheric optical turbulence conditions over the Ethiopian plateau during non-rainy season
Authors: Qing Chun , Bi Cuicui , Zhu Wenyue , Qian Xianmei , Kang Li , Li Xuebin , Wu Xiaoqing
Published: September 2023

A worldwide search is currently being conducted to determine the most appropriate sites for the next generation of large optical and infrared telescopes. Here, we report a global map of atmospheric optical turbulence-associated parameter (atmospheric coherence length) based on the fifth generation of European Centre for Medium Range Weather Forecasts re-analysis data set and results for atmospheric coherence lengths at European Southern Observatory and Tibetan Plateau locations (all at mid-latitudes). These confirm the accuracy of the global atmospheric optical turbulence model, but also the simulation result reveals that an excellent atmospheric calm site exist at the Ethiopian Plateau (at a latitude of ∼10°N) outside of the rainy season. The Ethiopian Plateau is the highest plateau in Africa, known as the ‘Roof of Africa’, with an average elevation of over 2500 m, and thus potentially provides good opportunities for astronomy and astrophysics. The median atmospheric coherence length at the Ethiopian Plateau was 17.7 cm and approximately 75 per cent of the time above 15.6 cm for dry conditions, indicating a very calm atmosphere. Although favourable atmospheric turbulence conditions at the Ethiopian Plateau were found from the global turbulence model, due to the complete lack of infrastructure it has never been visited, meaning that additional validation experiments are required.
Chemical enrichment of ICM within the Ophiuchus cluster I: radial profiles
Authors: Gatuzz Efrain , Sanders J S , Dennerl K , Liu A , Fabian A C , Pinto C , Eckert D , Walker S A , ZuHone J
Published: September 2023

The analysis of the elemental abundances in galaxy clusters offers valuable insights into the formation and evolution of galaxies. In this study, we explore the chemical enrichment of the intracluster medium in the Ophiuchus cluster by utilizing XMM–Newton EPIC-pn observations. We explore the radial profiles of Si, S, Ar, Ca, and Fe. Due to the high absorption of the system, we have obtained only upper limits for O, Ne, Mg, and Ni. We model the X/Fe ratio profiles with a linear combination of core-collapse supernovae (SNcc) and Type Ia supernovae (SNIa) models. We found a flat radial distribution of SNIa ratio over the total cluster enrichment $10\!-\!30{{\ \rm per\ cent}}$ for all radii. However, the absence of light α-elements abundances may lead to overestimation of the SNcc contribution.
Asteroseismology of double-mode radial δ Scuti stars: AE Ursae Majoris and RV Arietis
Authors: Daszyńska-Daszkiewicz J , Walczak P , Szewczuk W , Niewiadomski W
Published: September 2023

We construct complex seismic models of two high-amplitude δ Sct stars, AE UMa and RV Ari, each pulsating in two radial modes: fundamental and first overtone. Besides the frequencies of two radial modes, the models also reproduce the amplitude of bolometric flux variations (the non-adiabatic parameter f) for the dominant mode. Applying the Monte-Carlo-based Bayesian analysis, we derive strong constraints on the parameters of the model, as well as on the free parameters of the theory. A vast majority of seismic models of the two stars are just at the beginning of hydrogen-shell burning and a small fraction are at the very end of an overall contraction. The stars have a similar age of about 1.6 Gyr for the hydrogen-shell burning phase. Both stars have unusual low overshooting from the convective core, about 0.02 and 0.004 of the pressure scaleheight for AE UMa and RV Ari, respectively. This result presumably indicates that overshooting should vary with time and scale with a decreasing convective core. The efficiency of convection in the envelope of both stars is low and is described by the mixing length parameter αMLT of about 0.3–0.6. The third frequency of RV Ari, confirmed by us in the Transiting Exoplanet Survey Satellite (TESS) photometry, can only be associated with mixed non-radial modes ℓ = 1,  g4–g8 or ℓ = 2,  g10–g12. We include the dipole mode into our Bayesian modelling and demonstrate its huge asteroseismic potential.
Stellar bars in spinning haloes: delayed buckling and absence of slowdown
Authors: Li Xingchen , Shlosman Isaac , Heller Clayton , Pfenniger Daniel
Published: September 2023

We use numerical simulations to analyse the stellar bar evolution in spinning dark matter (DM) haloes. Previous works have shown the halo spin has a substantial effect on bar evolution and can lead to bar dissolution following the vertical buckling instability. We invoke the DM spin sequence, λ = 0–0.09, and study the effect of DM density along this λ sequence by varying compactness of DM halo. We find that (1) varying DM density has a profound effect on bar evolution along λ sequence. (2) For λ ≳ 0.045, the buckling has been delayed progressively. (3) Stellar bars remain near maximal strength, and their amplitude plateau stage extends over 0.7–5 Gyr, terminating with the buckling. (4) Although stellar bars remain strong during the plateau, their pattern speed and size stay nearly constant. This unusual behaviour of stellar bars follows from highly reduced gravitational torques due to DM bar being aligned with the stellar bar. The orbital analysis shows that delayed buckling results from slow evolution of stellar oscillations along bar major and vertical axes, thus postponing the action of the vertical 2:1 resonance which pumps the rotational energy into vertical motions. (5) Peanut/boxy-shaped bulges form at the beginning of the plateau and grow with time. (6) Finally, strong bars in spinning haloes can avoid fast braking, resolving the long-standing discrepancy between observations and N-body simulations. This behaviour of stellar bars along the λ and DM density sequences reveals a wealth of stellar bar properties which require additional study.
Genetic Origins and Adaptive Evolution of the Deng People on the Tibetan Plateau
Authors: Ge Xueling , Lu Yan , Chen Shuanghui , Gao Yang , Ma Lifeng , Liu Lijun , Liu Jiaojiao , Ma Xixian , Kang Longli , Xu Shuhua
Published: September 2023

The Tibetan Plateau is populated by diverse ethnic groups, but most of them are underrepresented in genomics studies compared with the Tibetans (TIB). Here, to gain further insight into the genetic diversity and evolutionary history of the people living in the Tibetan Plateau, we sequenced 54 whole genomes of the Deng people with high coverage (30–60×) and analyzed the data together with that of TIB and Sherpas, as well as 968 ancient Asian genomes and available archaic and modern human data. We identified 17.74 million novel single-nucleotide variants from the newly sequenced genomes, although the Deng people showed reduced genomic diversity and a relatively small effective population size. Compared with the other Tibetan highlander groups which are highly admixed, the Deng people are dominated by a sole ancestry that could be traced to some ancient northern East Asian populations. The divergence between Deng and Tibetan people (∼4,700–7,200 years) was more recent than that between highlanders and the Han Chinese (Deng-HAN, ∼9,000–14,000 years; TIB-HAN, 7,200–10,000 years). Adaptive genetic variants (AGVs) identified in the Deng are only partially shared with those previously reported in the TIB like HLA-DQB1, whereas others like KLHL12 were not reported in TIB. In contrast, the top candidate genes harboring AGVs as previously identified in TIB, like EPAS1 and EGLN1, do not show strong positive selection signals in Deng. Interestingly, Deng also showed a different archaic introgression scenario from that observed in the TIB. Our results suggest that convergent adaptation might be prevalent on the Tibetan Plateau.
Preclinical pediatric brain tumor models for immunotherapy: Hurdles and a way forward
Authors: Mishra Deepak Kumar , Popovski Dean , Morris Shelli M , Bondoc Andrew , Senthil Kumar Shiva , Girard Emily J , Rutka James , Fouladi Maryam , Huang Annie , Olson James M , Drissi Rachid
Published: September 2023

Brain tumors are the most common solid tumor in children and the leading cause of cancer-related deaths. Over the last few years, improvements have been made in the diagnosis and treatment of children with Central Nervous System tumors. Unfortunately, for many patients with high-grade tumors, the overall prognosis remains poor. Lower survival rates are partly attributed to the lack of efficacious therapies. The advent and success of immune checkpoint inhibitors (ICIs) in adults have sparked interest in investigating the utility of these therapies alone or in combination with other drug treatments in pediatric patients. However, to achieve improved clinical outcomes, the establishment and selection of relevant and robust preclinical pediatric high-grade brain tumor models is imperative. Here, we review the information that influenced our model selection as we embarked on an international collaborative study to test ICIs in combination with epigenetic modifying agents to enhance adaptive immunity to treat pediatric brain tumors. We also share challenges that we faced and potential solutions.
Hosting the Tobacco Industry Supply Chain and Political Interference
Authors: Hiscock Rosemary , Alaouie Hala , Matthes Britta K , Mehegan John , Bloomfield Michael J
Published: September 2023

Introduction

We found no comprehensive studies on the location of transnational tobacco and leaf company (TTLC) subsidiaries (business entities they control) or the consequences of their presence on health policy.

Aims and Methods

Here we assess (1) the global reach of TTLCs by mapping their tobacco growing and manufacturing subsidiaries and (2) the relationship between in-country presence of the tobacco industry and their power and interference. Data on subsidiaries were collated through systematic searching for countries’ supply chain activities in documents and web pages. Cross-sectional multiple regression analysis was used to assess the association between the number of agricultural and manufacturing TTLCs and the Tobacco Industry Interference score, and the degree to which these were mediated by tobacco control, good governance, and economic importance of tobacco.

Results

TTLC supply chain activity had global reach. As the number of TTLCs with tobacco growing and manufacturing activities rose, interference increased significantly. Interference was associated with poorer tobacco control. The association with more TTLCs undertaking final product manufacturing was related to higher-value tobacco exports but was not related to tobacco making a bigger contribution to the economy.

Conclusions

TTLCs continue to control the global tobacco supply chain through their globe-spanning subsidiaries. The presence of TTLCs in a country is associated with political interference. Countries should consider their participation in the tobacco supply chain alongside the understanding that they are likely to cede political power to TTLCs, potentially undermining the health of their populations.

Implications

Tobacco control research has traditionally concentrated on the demand side of tobacco. Our results lend support to calls for more research on the supply of tobacco. Governments should require tobacco companies to provide detailed, up-to-date information in an easily accessible format on in-country supply chain activities. Policymakers should take the likelihood of political interference in health and environmental policy into account when making decisions about foreign direct investment offered by the tobacco industry.
Molecular Bulkiness of a Single Amino Acid in the F1 α-Subunit Determines the Robustness of Cyanobacterial ATP Synthase
Authors: Machida Akito , Kondo Kumiko , Wakabayashi Ken-ichi , Tanaka Kan , Hisabori Toru
Published: September 2023

Cyanobacteria are promising photosynthetic organisms owing to their ease of genetic manipulation. Among them, Synechococcus elongatus UTEX 2973 exhibits faster growth, higher biomass production efficiency and more robust stress tolerance compared with S. elongatus PCC 7942. This is due to specific genetic differences, including four single-nucleotide polymorphisms (SNPs) in three genes. One of these SNPs alters an amino acid at position 252 of the FoF1 ATP synthase α-subunit from Tyr to Cys (αY252C) in S. elongatus 7942. This change has been shown to significantly affect growth rate and stress tolerance, specifically in S. elongatus. Furthermore, experimental substitutions with several other amino acids have been shown to alter the ATP synthesis rate in the cell. In the present study, we introduced identical amino acid substitutions into Synechocystis sp. PCC 6803 at position 252 to elucidate the amino acid’s significance and generality across cyanobacteria. We investigated the resulting impact on growth, intracellular enzyme complex levels, intracellular ATP levels and enzyme activity. The results showed that the αY252C substitution decreased growth rate and high-light tolerance. This indicates that a specific bulkiness of this amino acid’s side chain is important for maintaining cell growth. Additionally, a remarkable decrease in the membrane-bound enzyme complex level was observed. However, the αY252C substitution did not affect enzyme activity or intracellular ATP levels. Although the mechanism of growth suppression remains unknown, the amino acid at position 252 is expected to play an important role in enzyme complex formation.
A multitiered haplotype strategy to enhance phased assembly and fine mapping of a disease resistance locus
Authors: Zou Cheng , Sapkota Surya , Figueroa-Balderas Rosa , Glaubitz Jeff , Cantu Dario , Kingham Brewster F , Sun Qi , Cadle-Davidson Lance
Published: September 2023

Fine mapping of quantitative trait loci (QTL) to dissect the genetic basis of traits of interest is essential to modern breeding practice. Here, we employed a multitiered haplotypic marker system to increase fine mapping accuracy by constructing a chromosome-level, haplotype-resolved parental genome, accurate detection of recombination sites, and allele-specific characterization of the transcriptome. In the first tier of this system, we applied the preexisting panel of 2,000 rhAmpSeq core genome markers that is transferable across the entire Vitis genus and provides a genomic resolution of 200 kb to 1 Mb. The second tier consisted of high-density haplotypic markers generated from Illumina skim sequencing data for samples enriched for relevant recombinations, increasing the potential resolution to hundreds of base pairs. We used this approach to dissect a novel Resistance to Plasmopara viticola-33 (RPV33) locus conferring resistance to grapevine downy mildew, narrowing the candidate region to only 0.46 Mb. In the third tier, we used allele-specific RNA-seq analysis to identify a cluster of 3 putative disease resistance RPP13-like protein 2 genes located tandemly in a nonsyntenic insertion as candidates for the disease resistance trait. In addition, combining the rhAmpSeq core genome haplotype markers and skim sequencing–derived high-density haplotype markers enabled chromosomal-level scaffolding and phasing of the grape Vitis × doaniana ‘PI 588149’ assembly, initially built solely from Pacific Biosciences (PacBio) high-fidelity (HiFi) reads, leading to the correction of 16 large-scale phasing errors. Our mapping strategy integrates high-density, phased genetic information with individual reference genomes to pinpoint the genetic basis of QTLs and will likely be widely adopted in highly heterozygous species.
Stripe rust effector Pst21674 compromises wheat resistance by targeting transcription factor TaASR3
Authors: Zheng Peijing , Liu Mengxue , Pang Lijing , Sun Ruyi , Yao Mohan , Wang Xiaojie , Kang Zhensheng , Liu Jie
Published: September 2023

Pathogens compromise host defense responses by strategically secreting effector proteins. However, the molecular mechanisms by which effectors manipulate disease-resistance factors to evade host surveillance remain poorly understood. In this study, we characterized a Puccinia striiformis f. sp. tritici (Pst) effector Pst21674 with a signal peptide. Pst21674 was significantly upregulated during Pst infections in wheat (Triticum aestivum L.) and knocking down Pst21674 by host-induced gene silencing led to reduced Pst pathogenicity and restricted hyphal spread in wheat. Pst21674 interaction with the abscisic acid-, stress-, and ripening-induced protein TaASR3 was validated mainly in the nucleus. Size exclusion chromatography, bimolecular fluorescence complementation, and luciferase complementation imaging assays confirmed that TaASR3 could form a functional tetramer. Virus-induced gene silencing and overexpression demonstrated that TaASR3 contributes to wheat resistance to stripe rust by promoting accumulation of reactive oxygen species and cell death. Additionally, transcriptome analysis revealed that the expression of defense-related genes was regulated in transgenic wheat plants overexpressing TaASR3. Interaction between Pst21674 and TaASR3 interfered with the polymerization of TaASR3 and suppressed TaASR3-mediated transcriptional activation of defense-related genes. These results indicate that Pst21674 serves as an important virulence factor secreted into the host nucleus to impede wheat resistance to Pst, possibly by targeting and preventing polymerization of TaASR3.
Cuscuta campestrisfine-tunes gene expression during haustoriogenesis as an adaptation to different hosts
Authors: Bawin Thomas , Didriksen Alena , Faehn Corine , Olsen Stian , Sørensen Iben , Rose Jocelyn K C , Krause Kirsten
Published: September 2023

The Cuscuta genus comprises obligate parasitic plants that have an unusually wide host range. Whether Cuscuta uses different infection strategies for different hosts or whether the infection strategy is mechanistically and enzymatically conserved remains unknown. To address this, we investigated molecular events during the interaction between field dodder (Cuscuta campestris) and two host species of the Solanum genus that are known to react differently to parasitic infection. We found that host gene induction, particularly of cell wall fortifying genes, coincided with a differential induction of genes for cell wall degradation in the parasite in the cultivated tomato (Solanum lycopersicum) but not in a wild relative (Solanum pennellii). This indicates that the parasite can adjust its gene expression in response to its host. This idea was supported by the increased expression of C. campestris genes encoding an endo-β-1,4-mannanase in response to exposure of the parasite to purified mono- and polysaccharides in a host-independent infection system. Our results suggest multiple key roles of the host cell wall in determining the outcome of an infection attempt.
Improvement of sleep and pain with lemborexant administration in patients with chronic pain: a retrospective observational study
Authors: Ueno Kyohei , Sato Hitoaki , Nomura Yuki , Obata Norihiko , Mizobuchi Satoshi
Published: September 2023

Objective

Patients with chronic pain often have sleep disturbances, and many patients receive sleep medications in addition to analgesics. Although there have been scattered reports of negative pain–sleep interactions, only a few reports have investigated the efficacy of sleep medication interventions in patients with chronic pain for improving sleep disturbances and reducing pain. We retrospectively examined whether lemborexant, an orexin receptor antagonist, is effective in improving sleep disturbances and reducing pain in patients with chronic pain. This study was approved by the Ethics Committee of our hospital.

Methods

The subjects were 26 patients with chronic pain undergoing treatment at our pain clinic between July 2021 and March 2022, who had been diagnosed with insomnia, with an Athens Insomnia Scale (AIS) score of ≥6 and had been started on lemborexant. The AIS score and pain score (Numeric Rating Scale [NRS]) before and after 2 and 4 weeks of starting lemborexant were investigated.

Results

Patients who were already taking other sleep medications, such as benzodiazepines were switched to 5 mg of lemborexant after all the other sleep medications were discontinued. Those who had not yet used sleeping pills were started on 5 mg of lemborexant. During the study course, the dose of lemborexant was adjusted at the discretion of the attending physician, based on improvement of insomnia symptoms and secondary symptoms, such as daytime sleepiness and lightheadedness. The study finally included 21 patients, excluding 5 who could not continue taking lemborexant due to side effects, such as lightheadedness. The AIS scores significantly improved, decreasing from baseline (mean ± standard deviation: 12.5 ± 4.9) to 2 weeks (7.8 ± 3.1) and 4 weeks (5.3 ± 2.9) after the start of lemborexant. No significant difference was observed in the degree of improvement in sleep disturbance between patients with or without previous sleep medications, and there was also no statistically significant improvement in the NRS score before (6.1 ± 2.7) and after 2 weeks (5.5 ± 2.3) and 4 weeks (5.9 ± 2.2) from treatment initiation.
Small telescopes being effective: MAGIC or not?
Authors: Afanasiev Victor L , Malygin Eugene A , Shablovinskaya Elena S , Uklein Roman I , Amirkhanyan Vladimir R , Perepelitsyn Alexander E , Afanasieva Irina V
Published: September 2023

The paper describes the MAGIC multimode focal reducer (Monitoring of Active Galaxies by Investigation of their Cores), commissioned on the 1-m Zeiss-1000 telescope of the Special Astrophysical Observatory of the Russian Academy of Sciences in 2020 September. Three observational modes are currently realized: photometry, polarimetry, and long-slit spectroscopy. Reducing the focal length makes it possible to obtain a sufficiently large field of view for photometry and a large slit height for spectroscopy of ∼12′ , as well as a large field of view for polarimetry with a quadrupole Wollaston prism of ∼6${_{.}^{\prime}}$4. This feature makes the complex study of extended nebulae and galaxies efficient. The MAGIC capabilities are presented in examples of observations of various astronomical objects. The spectral mode in the range of 4000–7200 ÅÅ provides the spectral resolution R ∼ 1000; for a starlike target up to 14 mag in medium-band filters with a seeing of 1″ for 20 min of total exposure, the photometry accuracy is better than 0.01 mag and the polarization accuracy is better than 0.6 per cent. Especially for the new focal reducer, an offset guide and a position angle rotation system were implemented. The results of the modernization of the baffle system in the optical scheme of the telescope for the suppression of scattered light are also described.
Metabolic disturbance and transcriptomic changes induced by methyl triclosan in human hepatocyte L02 cells
Authors: An Jing , Yi Yuting , Jiang Jingjing , Yao Weiwei , Ren Guofa , Shang Yu
Published: September 2023

Purpose: Methyl triclosan (MTCS) is one of the biomethylated by-products of triclosan (TCS). With the increasing use of TCS, the adverse effects of MTCS have attracted extensive attention in recent years. The purpose of this study was to investigate the cytotoxicity of MTCS and to explore the underlining mechanism using human hepatocyte L02 cells as in vitro model. Results: The cytotoxicity results revealed that MTCS could inhibit cell viability, disturb the ratio of reduced glutathione (GSH) and oxidized glutathione (GSSG), and reduce the mitochondrial membrane potential (MMP) in a dose-dependent manner. In addition, MTCS exposure significantly promoted the cellular metabolic process, including enhanced conversion of glucose to lactic acid, and elevated content of intracellular triglyceride (TG) and total cholesterol (TC). RNA-sequencing and bioinformatics analysis indicated disorder of glucose and lipid metabolism was significantly induced after MTCS exposure. Protein-protein interaction network analysis and node identification suggested that Serine hydroxy methyltransferase 2 (SHMT2), Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), Asparagine synthetase (ASNS) and Phosphoglycerate dehydrogenase (PHGDH) are potential molecular markers of metabolism imbalance induced by MTCS. Conclusion: These results demonstrated that oxidative stress and metabolism dysregulation might be involved in the cytotoxicity of MTCS in L02 cells.