bluuebunny/crossref_metadata_2025 huggingface dataset:
Some university experiences of aircraft simulator research
Authors: Chapleo A. Q.
Published: March 2023

My department's involvement in flight simulation started in the early 1960s under Professor Stephens. At that time, and even more so subsequently, what I think is an unusually high proportion of our staff had previous experience either as pilots, or in flight testing. Since 1965 we have operated our own light aircraft, primarily for flight test work at undergraduate level. In addition our links with the University Air Squadron are strong and the number of our students who are members is also exceptional. Every project described here, apart from one, was done by a pilot, or ex-pilot.

Our first project, for a PhD, was somewhat exploratory in nature, consisting as it did of three largely unrelated investigations. The first of these, suggested by two accidents involving aircraft on ground controlled approaches (GCA), was tackled using a fixed-base simulator consisting of a spring-loaded pitch control and throttle, and the usual flight instruments, all under a hood. I should explain that the GCA, particularly favoured by the military as an approach technique, consists of precision ground radar giving information of azimuth and elevation relative to the desired line of approach, to a ground controller. The ground controller then passes instructions to the pilot such as: ‘You are 30 ft below the glidepath. Adjust your rate of descent and turn left three degrees.’
The M.45SD-02 variable pitch geared fan engine demonstrator test and evaluation experience
Authors: Wright G. H. , Russell J. G.
Published: March 2023

In the early 1970s considerable attention was being given to the possibilities of short-haul aircraft aimed at operating into or near city centres. There was a belief that suitable airfield sites could be found if field lengths no greater than about 2000 ft-3000 ft were required into which the aircraft could operate quietly with steep climb out and approach.
Recent developments in helicopter noise reduction
Authors: Sternfeld Harry
Published: March 2023

The helicopter industry has been experiencing a dramatic conversion from a market which was almost completely dominated by the military, to one in which the civil customer is playing an ever increasing role. As part of this change there is an increasing demand for vehicles whose interior noise levels are substantially lower than those of their predecessors.

One of the most significant recent events in the area of helicopter noise has been an impending regulatory action, rather than a technological breakthrough. This action is the development of helicopter noise standards which are currently being considered simultaneously by the International Congress of Aeronautical Organisation's (ICAO) and by the Federal Aviation Administration (FAA) in the United States. Up to the present time the specification of external noise limits, if any, were either made by individual customers, based on a particular need, or by the designer and manufacturer who might try to forecast how noisy the aircraft could be and still meet market requirements. It is highly probable that the effect of the new standards will be to require future helicopters to be substantially quieter than many of the current models.
The 1-4-1 system of jack movements for the flexible liners of supersonic wind tunnels
Authors: McIntosh A. C. , Pike J.
Published: March 2023

A method of improving the flow angle and Mach number distribution of a flexible-plate supersonic wind tunnel by small movements of the top and bottom liners has been known for a number of years. Once the influence on the flow, at a given Mach number, of small displacements of jacks supporting the liners are known, jack movements can be used to reduce non-uniformities in the working section flow. Such a procedure is being studied for adjusting the flow in the 8 ft x 8 ft Supersonic Wind Tunnel at RAE Bedford. However, one of the main difficulties encountered has been that of accurately determining the influence of each jack. The extended rippling in the plate which results from a displacement of a single jack generates a Mach number disturbance which is difficult to trace. This is particularly true at lower Mach numbers (i.e. near M=l.4) where the reflection of the disturbance from the opposite wall is observed to combine with the ‘tail’ of the direct effect, thereby causing interference effects in the data. Even with a 9-tube pitot rake spanning the tunnel it is difficult to ascertain which part of the disturbance is coming from the top of the tunnel and which part from the bottom. Ways have therefore been considered of moving the plate in the region of a particular jack in such a manner that the resulting waveform is shorter and more readily traced. A simple but effective system of jack movement has been derived and is described here as the 1-4-1 system.
The future of data processing in aerospace
Authors: Mueller George E.
Published: March 2023

Future developments and trends in the data processing industry will have an earlier and stronger impact on aerospace than upon any other segment of industry. The use of data processing by aerospace in scientific, administrative and automation applications typically precedes and anticipates that of society and industry at large. My discussion, therefore, will focus on the total use of data processing and its technologies in our industrial-based societies. First, I will present an overview of data processing in terms of usage and dollars, then look at the world of computers a decade hence from a user's and administrator's point of view. Then I will offer a view of that world of computers from a technologist's point of view, and finally, discuss the impact of such a scenario on our society.

The term data processing industry, as I will use it, includes all those who are involved in providing data processing capabilities: equipment and software manufacturers, programming and operations staffs of user installations, professional data processing organisations, and university and research computer science groups. In short, those who design and produce our computer-based systems and services.
Safety aspects of the aerial application of pesticides
Authors: Quantick H. R.
Published: March 2023

Pesticides help to protect man, plants, animals, structures and various goods from injury, disease or destruction. They maintain and improve our food supply and public health. In some cases, actual economic survival is dependent upon these chemicals.

Although biological and integrated control play an important role in our overall control of pests, we must still rely, to a large extent, upon chemicals to control or suppress the majority of pests. Although there are other methods of controlling insects and pests by biological and physical means, the object is to prevent pest damage of economic significance by the most compatible, acceptable, efficient and economic method.

At the present time, this means chemicals, and in many cases, the rapid application to match an insect invasion, a vector-borne disease outbreak or application in inaccessable areas requires aircraft to apply them.
Inventing the ‘Maritime Silk Road’
Authors: Sen Tansen
Published: March 2023

Although inspired by the nineteenth-century term ‘Silk Road(s)’, the phrase ‘Maritime Silk Road’ has its own origins, connotations, and applications. This article examines the emergence of the latter term as a China-centric concept and its various entanglements since the early 1980s, involving the People’s Republic of China’s (PRC) political bodies, academia, the ‘open door’ policy, the pursuit of World Heritage listings, and the current ‘Belt and Road Initiative’. These entanglements, the article contends, have resulted in the emergence of what could be called a ‘Maritime Silk Road’ ecosystem in the PRC. The analysis of this ecosystem presented in the article reveals not only the processes through which a narrative on China’s engagement with the maritime world has been constructed over time, but also its association with issues of national pride, heritage- and tradition-making, foreign-policy objectives, and claims to territorial sovereignty. As such, the ‘Maritime Silk Road’ must be understood as a concept that is intimately entwined with the recent history of the PRC and distinct from its nineteenth-century antecedent, which was used as a label for overland connectivity.
Commemorating the Virgin Mary at Barking Abbey: Cambridge, University Library, Dd.12.56
Authors: YARDLEY ANNE BAGNALL
Published: March 2023

This article examines the unusual commemorative Office of the Virgin from Barking Abbey in a fifteenth-century book of hours, Cambridge, University Library, Dd.12.56 (hereafter Dd.12.56). As already evident in the Barking Ordinal, the nuns of this Abbey venerated Mary, one of their patron saints, with a weekly full three-nocturn, twelve-lesson Matins service. Dd.12.56, however, has only recently been linked to Barking Abbey and drawing on new material in this manuscript in correlation with others from the Abbey, I argue that the Barking nuns compiled a unique series of readings and responsories to honour Mary. The progression through the three nocturns of Matins articulates a Marian theology that intersects with the nuns’ self-understanding and I demonstrate that they carefully crafted the lesser hours to highlight specific times of day and to complement Marian hymns sung at Barking. The accepted belief that books of hours were for personal devotion obscures the possibility that such books reflect communal liturgical practices, potentially serving multiple purposes within a monastic setting. Although Dd.12.56 dates from the fifteenth century, it may testify to a much older liturgical practice, which originated in the twelfth century when the three-nocturn format was still prevalent in Benedictine use and before it was largely replaced by a two-nocturn format in the thirteenth century. Benedictine tradition offered individual monastic houses the opportunity to craft this service. Dd.12.56 stands as a new and important testimony to the rich and imaginative ways in which the Barking community created, collated and curated materials that they steeped in their minds and hearts.
Functional idiosyncrasies of suggesting constructions in British English
Authors: SUNG MIN-CHANG
Published: March 2023

This study aims to examine functional idiosyncrasies of seemingly synonymous constructions and explain their frequency distributions in different spoken registers. To this end, lexical and discoursal approaches in the corpus-based research of constructions are combined to investigate how significant collocates of three suggesting constructions – namely, let's, what/how about and why don't you/we – are contextually situated in British English. Constructional analyses of the spoken part of the British National Corpus show that the three suggesting constructions primarily perform different metadiscourse and directive functions. Based on these functional variations, the present study explains the distribution and usage of the three suggesting constructions across the five spoken registers.
CANONICITY IN POWER AND MODAL LOGICS OF FINITE ACHRONAL WIDTH
Authors: GOLDBLATT ROBERT , HODKINSON IAN
Published: March 2023

We develop a method for showing that various modal logics that are valid in their countably generated canonical Kripke frames must also be valid in their uncountably generated ones. This is applied to many systems, including the logics of finite width, and a broader class of multimodal logics of ‘finite achronal width’ that are introduced here.
Subclinical vascular damage in Schistosoma spp. endemic	regions
Authors: Silvestri Valeria , Mshana Mwanahawa Idavas , Mushi Vivian , Bonaventura Witness M. , Justine Nyanda C. , Kinabo Clemence , Zacharia Abdallah , La Torre Giuseppe , Ngasala Billy
Published: March 2023

Summary: Background: Cardiovascular abnormalities have been described in patients with schistosomiasis. Their true prevalence and clinical features in endemic settings are unknown. Patients and methods: The study aimed to assess the prevalence of subclinical cardiovascular damage in a population endemic to schistosomiasis. A cross-sectional study was conducted using colour-ultrasound assessment of abdominal and carotid arteries among adults aged >18 years living in Kome Island, Tanzania. Carotid intimal medial thickness, carotid plaque, mean abdominal aortic diameter, and presence of aneurysms were assessed. Anamnestic data on previous Schistosoma infection was collected; the actual prevalence of Schistosoma mansoni and Schistosoma haematobium was also assessed through stool and urine investigations. Results: A total of 264 participants (166 female, 98 male) were enrolled (mean age of 50±15.5 years). The history of previous schistosomiasis was 27.3%, and actual positivity for Schistosoma mansoni was 5.9%. The Latero-lateral Abdominal Aortic Diameter was significantly increased among participants with a previous history of schistosomiasis (16.7±2.8 mm vs. 17.6±3 mm; p=0.02), with an aOR of 1.15 [CI 1.04–1.28]; p=0.007]. Conclusions: The significant difference in the Latero-lateral Abdominal Aortic Diameter in participants with a previous history of schistosomiasis suggests the need for further investigations on aortic damage in endemic populations, independently from the positive laboratory investigations.
The Urban Lightning Effect Revealed With Geostationary Lightning Mapper Observations
Authors: Burke J. D. , Shepherd Marshall
Published: March 2023

Within the Charlotte, North Carolina, to Atlanta, Georgia, megaregion (Charlanta), the Atlanta metropolitan area has been shown to augment proximal cloud‐to‐ground (CG) lightning occurrence. Although numerous studies have documented this “urban lightning effect” (ULE) with regard to CG lightning, relatively few have investigated urban effects on distributions of total lightning (TL). Moreover, there has yet to be a study of the ULE using TL observations from the Geostationary Lightning Mapper (GLM). In an effort to fill this gap, we investigated spatial distributions of TL around the cities of Atlanta, GA, Greenville, SC, and Charlotte, NC, using GLM data collected during the warm seasons of 2018–2021. Analyses reveal augmentation of TL intensity and frequency over the major cities of Atlanta and Charlotte, with a diminished urban signal over the smaller city of Greenville. This work also demonstrated the potential efficacy of the emerging satellite‐based TL climatology in ULE studies.
Quaternary Magnetic Stratigraphy of Deep‐Sea Sediments in the Western North Pacific: Influences of Paleomagnetic Recording Efficiency and Lock‐In Delay
Authors: Shin Ji Young , Kim Wonnyon , Seong Yeong‐Bae , Chang Liao
Published: March 2023

Understanding past environmental changes in the western North Pacific is rather limited due to the general paucity of robust chronology for carbonate‐lacking pelagic clay sediments. Here, we present a new magnetostratigraphy of Quaternary deep‐sea sediments in the northern Mariana Basin. A comprehensive set of paleomagnetic, rock magnetic, and microscopic results reveal that paleomagnetic signals are mainly carried by detrital magnetic minerals of Asian eolian dust and volcanic origins. The volcanic materials, most likely from the Mariana Arc, are characterized by low coercivity (∼30 mT) interacting single domain (SD) and pseudo‐SD grains, associated with abundant dendritic magnetic crystals/inclusions. This volcanic component is a suitable remanence carrier but is less efficient in recording geomagnetic intensity than the higher coercivity eolian component. The relative paleointensity record derived with minimum rock magnetic artifacts shows comparable patterns with global templates. At the Matuyama‐Brunhes transition, a ∼2‐cm remanence lock‐in depth offset is identified from beryllium isotope records, and the estimated magnetostratigraphic age delay is small (∼8 kyr). Our results provide an improved understanding of remanence recording processes in carbonate‐poor deep‐sea clays and demonstrate magnetic stratigraphy as a valuable chronology in the western North Pacific region.
The Mid‐Lithospheric Discontinuity Caused by Channel Flow in Proto‐Cratonic Mantle
Authors: Yang Haibin , Artemieva Irina M. , Thybo Hans
Published: March 2023

Global geophysical observations show the presence of the enigmatic mid‐lithospheric discontinuity (MLD) at depths of ca. 80–150 km which may question the stability and internal structure of the continental lithosphere. While various mechanisms may explain the MLD, the dynamic processes leading to the seismic observations are unclear. Here we present a physical mechanism for the origin of MLD by channel flow in the cratonic mantle lithosphere, triggered by convective instabilities at cratonic margins in the Archean when the mantle was hot. Our numerical modeling shows that the top of the frozen‐in channel flow creates a shear zone at a depth comparable to the globally observed seismic MLD. Grain size reduction in the shear zone and accumulation of percolated melts or fluids along the channel top may reduce seismic wave speeds as observed below the MLD, while the channel flow itself may explain radial anisotropy of seismic wave speeds and change in direction of the seismic anisotropic fast axis. The proposed mechanism is valid for a broad range of physically realistic parameters and that MLD may have been preserved since its formation in the Archean. The intensity of the channel flow ceased with time due to secular cooling of the Earth's interior. The new mechanism may reshape our understanding of the evolution and stability of cratonic lithosphere.
Iron Loss During Continental Weathering in the Early Carboniferous Period Recorded by Karst Bauxites
Authors: Ling Kunyue , Wen Hanjie , Fan Haifeng , Zhu Xiangkun , Li Zhihong , Zhang Zhengwei , Grasby Stephen E.
Published: March 2023

Significant iron (Fe) loss can occur during continental weathering and efflux to the ocean via runoff, historically affecting global Fe cycling and marine ecosystems. Here, we report extremely low Fe content in early Carboniferous (ca. 340 Ma) bauxites in southwestern China. These bauxites were formed by redeposition of terrestrial soils along the paleo‐continental margin of the western South China Plate in warm climates. The bauxites contain high δ56Fe (−0.17‰ to +1.15‰) values with a negative correlation between Fe2O3 and δ56Fe, indicating that a substantial amount of Fe(III) was reduced to isotopically light dissolved Fe(II) and effuxed to the ocean via reductive dissolution under anoxic conditions. The low Corg content and low FeHR/FeT, Mo/Al, U/Al, and V/Al ratios of bauxite suggest that this reduction process occurred during the pedogenic (continental weathering) rather than the depositional/diagenetic stage of karst bauxite formation. Most of the dissolved Fe(II) were rapidly re‐oxidized to Fe(III) and transported toward the paleo‐continental margin forming iron ores with δ56Fe values around zero (−0.13‰ to +0.16‰). The negative correlation between Al2O3 and Fe2O3 contents in global karst bauxites suggests common Fe loss processes during continental weathering in geological periods favoring karst bauxite formation, such as during the Carboniferous, Permian, and Cretaceous periods and the Cenozoic era. Karst bauxite may thus provide a record of Fe loss during continental weathering and act as an indicator of enhanced Fe flux to oceans.
A Robust Estimate of Continental‐Scale Terrestrial Carbon Sinks Using GOSAT XCO2 Retrievals
Authors: Zhang Lingyu , Jiang Fei , He Wei , Wu Mousong , Wang Jun , Ju Weimin , Wang Hengmao , Zhang Yongguang , Sitch Stephen , Walker Anthony P. , Yue Xu , Feng Shuzhuang , Jia Mengwei , Chen Jing M.
Published: March 2023

Satellite XCO2 retrievals could improve the estimates of surface carbon fluxes, but it remains unknown on what scales these estimates are robust. Here, we use the time‐dependent Bayesian synthesis top‐down method and prior net ecosystem exchanges (NEEs) from 12 terrestrial biosphere models (TBMs) to infer the monthly carbon fluxes of 51 land regions with constraints by GOSAT XCO2 retrievals. We find that the uncertainty (standard deviation of 12 TBMs) reduction rates (uncertainty reduction rate (URR)) decrease significantly at decreasing spatial scales. On the continental‐scale, the mean URR is about 57%, and the annual and seasonal cycle estimates of NEE are rather robust. The evaluation shows that the posterior CO2 concentrations are significantly improved at the continental scale. Our study suggests that the GOSAT XCO2 can only promise a robust continental‐scale NEE estimate, and improving the XCO2 accuracy is an effective way to achieve robust estimates on smaller scales under current spatial coverage.
Cooperative antibiotic resistance facilitates horizontal gene transfer
Authors: Wang Qinqin , Wei Shaodong , Silva Ana Filipa , Madsen Jonas Stenløkke
Published: March 2023

The rise of β-lactam resistance among pathogenic bacteria, due to the horizontal transfer of plasmid-encoded β-lactamases, is a current global health crisis. Importantly, β-lactam hydrolyzation by β-lactamases, not only protects the producing cells but also sensitive neighboring cells cooperatively. Yet, how such cooperative traits affect plasmid transmission and maintenance is currently poorly understood. Here we experimentally show that KPC-2 β-lactamase expression and extracellular activity were higher when encoded on plasmids compared with the chromosome, resulting in the elevated rescue of sensitive non-producers. This facilitated efficient plasmid transfer to the rescued non-producers and expanded the potential plasmid recipient pool and the probability of plasmid transfer to new genotypes. Social conversion of non-producers by conjugation was efficient yet not absolute. Non-cooperative plasmids, not encoding KPC-2, were moderately more competitive than cooperative plasmids when β-lactam antibiotics were absent. However, in the presence of a β-lactam antibiotic, strains with non-cooperative plasmids were efficiently outcompeted. Moreover, plasmid-free non-producers were more competitive than non-producers imposed with the metabolic burden of a plasmid. Our results suggest that cooperative antibiotic resistance especially promotes the fitness of replicons that transfer horizontally such as conjugative plasmids.
The impact of childhood glaucoma on psychosocial functioning and quality of life: a review of the literature
Authors: McLaughlin Danielle E. , Semrov Ana , Munshi Hounsh , Patel Annika J. , Rahi Jugnoo , Grajewski Alana L. ,   Balkan CGRN Study Group, Bitrian Elena , Brandt James D. , Chang Ta Chen , Dada Tanuj , Delamater Alan , Edmunds Beth , Freedman Sharon F. , Hodapp Elizabeth , Kim Youngmee
Published: March 2023

We present a novel comprehensive literature review of studies of the psychosocial functioning (PF) and quality of life (QoL) of patients with childhood glaucoma and their caregivers. Our findings demonstrate variable study quality and approach, as well as inconsistent results relating to the association of glaucoma-specific factors and sociodemographic variables with measured PF and QoL. Future studies should focus on the development of culturally cognizant and standardized assessment tools, execution of multi-center longitudinal studies with global representation, evaluation of PF and QoL among siblings and childhood glaucoma providers, and implementation of interventions to improve patient and caregiver PF and QoL.
Epigenetic state determines the in vivo efficacy of STING agonist therapy
Authors: Falahat Rana , Berglund Anders , Perez-Villarroel Patricio , Putney Ryan M. , Hamaidi Imene , Kim Sungjune , Pilon-Thomas Shari , Barber Glen N. , Mulé James J.
Published: March 2023

While STING-activating agents have shown limited efficacy in early-phase clinical trials, multiple lines of evidence suggest the importance of tumor cell-intrinsic STING function in mediating antitumor immune responses. Although STING signaling is impaired in human melanoma, its restoration through epigenetic reprogramming can augment its antigenicity and T cell recognition. In this study, we show that reversal of methylation silencing of STING in murine melanoma cell lines using a clinically available DNA methylation inhibitor can improve agonist-induced STING activation and type-I IFN induction, which, in tumor-bearing mice, can induce tumor regression through a CD8+ T cell-dependent immune response. These findings not only provide mechanistic insight into how STING signaling dysfunction in tumor cells can contribute to impaired responses to STING agonist therapy, but also suggest that pharmacological restoration of STING signaling through epigenetic reprogramming might improve the therapeutic efficacy of STING agonists.
Rescue of astrocyte activity by the calcium sensor STIM1 restores long-term synaptic plasticity in female mice modelling Alzheimer’s disease
Authors: Lia Annamaria , Sansevero Gabriele , Chiavegato Angela , Sbrissa Miriana , Pendin Diana , Mariotti Letizia , Pozzan Tullio , Berardi Nicoletta , Carmignoto Giorgio , Fasolato Cristina , Zonta Micaela
Published: March 2023

Calcium dynamics in astrocytes represent a fundamental signal that through gliotransmitter release regulates synaptic plasticity and behaviour. Here we present a longitudinal study in the PS2APP mouse model of Alzheimer’s disease (AD) linking astrocyte Ca2+ hypoactivity to memory loss. At the onset of plaque deposition, somatosensory cortical astrocytes of AD female mice exhibit a drastic reduction of Ca2+ signaling, closely associated with decreased endoplasmic reticulum Ca2+ concentration and reduced expression of the Ca2+ sensor STIM1. In parallel, astrocyte-dependent long-term synaptic plasticity declines in the somatosensory circuitry, anticipating specific tactile memory loss. Notably, we show that both astrocyte Ca2+ signaling and long-term synaptic plasticity are fully recovered by selective STIM1 overexpression in astrocytes. Our data unveil astrocyte Ca2+ hypoactivity in neocortical astrocytes as a functional hallmark of early AD stages and indicate astrocytic STIM1 as a target to rescue memory deficits.
Integrated analysis of genomic and transcriptomic data for the discovery of splice-associated variants in cancer
Authors: Cotto Kelsy C. , Feng Yang-Yang , Ramu Avinash , Richters Megan , Freshour Sharon L. , Skidmore Zachary L. , Xia Huiming , McMichael Joshua F. , Kunisaki Jason , Campbell Katie M. , Chen Timothy Hung-Po , Rozycki Emily B. , Adkins Douglas , Devarakonda Siddhartha , Sankararaman Sumithra , Lin Yiing , Chapman William C. , Maher Christopher A. , Arora Vivek , Dunn Gavin P. , Uppaluri Ravindra , Govindan Ramaswamy , Griffith Obi L. , Griffith Malachi
Published: March 2023

Somatic mutations within non-coding regions and even exons may have unidentified regulatory consequences that are often overlooked in analysis workflows. Here we present RegTools (www.regtools.org), a computationally efficient, free, and open-source software package designed to integrate somatic variants from genomic data with splice junctions from bulk or single cell transcriptomic data to identify variants that may cause aberrant splicing. We apply RegTools to over 9000 tumor samples with both tumor DNA and RNA sequence data. RegTools discovers 235,778 events where a splice-associated variant significantly increases the splicing of a particular junction, across 158,200 unique variants and 131,212 unique junctions. To characterize these somatic variants and their associated splice isoforms, we annotate them with the Variant Effect Predictor, SpliceAI, and Genotype-Tissue Expression junction counts and compare our results to other tools that integrate genomic and transcriptomic data. While many events are corroborated by the aforementioned tools, the flexibility of RegTools also allows us to identify splice-associated variants in known cancer drivers, such asTP53,CDKN2A, andB2M, and other genes.
IGFBP5 is an ROR1 ligand promoting glioblastoma invasion via ROR1/HER2-CREB signaling axis
Authors: Lin Weiwei , Niu Rui , Park Seong-Min , Zou Yan , Kim Sung Soo , Xia Xue , Xing Songge , Yang Qingshan , Sun Xinhong , Yuan Zheng , Zhou Shuchang , Zhang Dongya , Kwon Hyung Joon , Park Saewhan , Il Kim Chan , Koo Harim , Liu Yang , Wu Haigang , Zheng Meng , Yoo Heon , Shi Bingyang , Park Jong Bae , Yin Jinlong
Published: March 2023

Diffuse infiltration is the main reason for therapeutic resistance and recurrence in glioblastoma (GBM). However, potential targeted therapies for GBM stem-like cell (GSC) which is responsible for GBM invasion are limited. Herein, we report Insulin-like Growth Factor-Binding Protein 5 (IGFBP5) is a ligand for Receptor tyrosine kinase like Orphan Receptor 1 (ROR1), as a promising target for GSC invasion. Using a GSC-derived brain tumor model, GSCs were characterized into invasive or non-invasive subtypes, and RNA sequencing analysis revealed that IGFBP5 was differentially expressed between these two subtypes. GSC invasion capacity was inhibited by IGFBP5 knockdown and enhanced by IGFBP5 overexpression both in vitro and in vivo, particularly in a patient-derived xenograft model. IGFBP5 binds to ROR1 and facilitates ROR1/HER2 heterodimer formation, followed by inducing CREB-mediated ETV5 and FBXW9 expression, thereby promoting GSC invasion and tumorigenesis. Importantly, using a tumor-specific targeting and penetrating nanocapsule-mediated delivery of CRISPR/Cas9-based IGFBP5 gene editing significantly suppressed GSC invasion and downstream gene expression, and prolonged the survival of orthotopic tumor-bearing mice. Collectively, our data reveal that IGFBP5-ROR1/HER2-CREB signaling axis as a potential GBM therapeutic target.
A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth
Authors: Wang Chong , Liu Xiang , Liang Jun , Narita Yohei , Ding Weiyue , Li Difei , Zhang Luyao , Wang Hongbo , Leong Merrin Man Long , Hou Isabella , Gerdt Catherine , Jiang Chang , Zhong Qian , Tang Zhonghui , Forney Carmy , Kottyan Leah , Weirauch Matthew T. , Gewurz Benjamin E. , Zeng Mu-sheng , Jiang Sizun , Teng Mingxiang , Zhao Bo
Published: March 2023

Epstein-Barr virus (EBV) immortalization of resting B lymphocytes (RBLs) to lymphoblastoid cell lines (LCLs) models human DNA tumor virus oncogenesis. RBL and LCL chromatin interaction maps are compared to identify the spatial and temporal genome architectural changes during EBV B cell transformation. EBV induces global genome reorganization where contact domains frequently merge or subdivide during transformation. Repressed B compartments in RBLs frequently switch to active A compartments in LCLs. LCLs gain 40% new contact domain boundaries. Newly gained LCL boundaries have strong CTCF binding at their borders while in RBLs, the same sites have much less CTCF binding. Some LCL CTCF sites also have EBV nuclear antigen (EBNA) leader protein EBNALP binding. LCLs have more local interactions than RBLs at LCL dependency factors and super-enhancer targets. RNA Pol II HiChIP and FISH of RBL and LCL further validate the Hi-C results. EBNA3A inactivation globally alters LCL genome interactions. EBNA3A inactivation reduces CTCF and RAD21 DNA binding. EBNA3C inactivation rewires the looping at the CDKN2A/B and AICDA loci. Disruption of a CTCF site at AICDA locus increases AICDA expression. These data suggest that EBV controls lymphocyte growth by globally reorganizing host genome architecture to facilitate the expression of key oncogenes.
RBFOX2 modulates a metastatic signature of alternative splicing in pancreatic cancer
Authors: Jbara Amina , Lin Kuan-Ting , Stossel Chani , Siegfried Zahava , Shqerat Haya , Amar-Schwartz Adi , Elyada Ela , Mogilevsky Maxim , Raitses-Gurevich Maria , Johnson Jared L. , Yaron Tomer M. , Ovadia Ofek , Jang Gun Ho , Danan-Gotthold Miri , Cantley Lewis C. , Levanon Erez Y. , Gallinger Steven , Krainer Adrian R. , Golan Talia , Karni Rotem
Published: March 2023

Pancreatic ductal adenocarcinoma (PDA) is characterized by aggressive local invasion and metastatic spread, leading to high lethality. Although driver gene mutations during PDA progression are conserved, no specific mutation is correlated with the dissemination of metastases1–3. Here we analysed RNA splicing data of a large cohort of primary and metastatic PDA tumours to identify differentially spliced events that correlate with PDA progression. De novo motif analysis of these events detected enrichment of motifs with high similarity to the RBFOX2 motif. Overexpression of RBFOX2 in a patient-derived xenograft (PDX) metastatic PDA cell line drastically reduced the metastatic potential of these cells in vitro and in vivo, whereas depletion of RBFOX2 in primary pancreatic tumour cell lines increased the metastatic potential of these cells. These findings support the role of RBFOX2 as a potent metastatic suppressor in PDA. RNA-sequencing and splicing analysis of RBFOX2 target genes revealed enrichment of genes in the RHO GTPase pathways, suggesting a role of RBFOX2 splicing activity in cytoskeletal organization and focal adhesion formation. Modulation of RBFOX2-regulated splicing events, such as via myosin phosphatase RHO-interacting protein (MPRIP), is associated with PDA metastases, altered cytoskeletal organization and the induction of focal adhesion formation. Our results implicate the splicing-regulatory function of RBFOX2 as a tumour suppressor in PDA and suggest a therapeutic approach for metastatic PDA.
Genome assembly of the ectoparasitoid wasp Theocolax elegans
Authors: Xiao Shan , Ye Xinhai , Wang Shuping , Yang Yi , Fang Qi , Wang Fang , Ye Gongyin
Published: March 2023

The ectoparasitoid waspTheocolax elegansis a cosmopolitan and generalist pteromalid parasitoid of several major storage insect pests, and can effectively suppress a host population in warehouses. However, little molecular information about this wasp is currently available. In this study, we assembled the genome ofT. elegansusing PacBio long-read sequencing, Illumina sequencing, and Hi-C methods. The genome assembly is 662.73 Mb in length with contig and scaffold N50 values of 1.15 Mb and 88.8 Mb, respectively. The genome contains 56.4% repeat sequences and 23,212 protein-coding genes were annotated. Phylogenomic analyses revealed thatT. elegansdiverged from the lineage leading to subfamily Pteromalinae (Nasonia vitripennisandPteromalus puparum) approximately 110.5 million years ago. We identified 130 significantly expanded gene families, 34 contracted families, 248 fast-evolving genes, and 365 positively selected genes inT. elegans. Additionally, 260 olfactory receptors and 285 venom proteins were identified. This genome assembly provides valuable genetic bases for future investigations on evolution, molecular biology and application ofT. elegans.
CACNA1D overexpression and voltage-gated calcium channels in prostate cancer during androgen deprivation
Authors: McKerr Niamh , Mohd-Sarip Adone , Dorrian Hannah , Breen Conor , A. James Jacqueline , McQuaid Stephen , Mills Ian G. , McCloskey Karen D.
Published: March 2023

Prostate cancer is often treated by perturbing androgen receptor signalling. CACNA1D, encoding CaV1.3 ion channels is upregulated in prostate cancer. Here we show how hormone therapy affects CACNA1D expression and CaV1.3 function. Human prostate cells (LNCaP, VCaP, C4-2B, normal RWPE-1) and a tissue microarray were used. Cells were treated with anti-androgen drug, Enzalutamide (ENZ) or androgen-removal from media, mimicking androgen-deprivation therapy (ADT). Proliferation assays, qPCR, Western blot, immunofluorescence, Ca2+-imaging and patch-clamp electrophysiology were performed. Nifedipine, Bay K 8644 (CaV1.3 inhibitor, activator), mibefradil, Ni2+ (CaV3.2 inhibitors) and high K+ depolarising solution were employed. CACNA1D and CaV1.3 protein are overexpressed in prostate tumours and CACNA1D was overexpressed in androgen-sensitive prostate cancer cells. In LNCaP, ADT or ENZ increased CACNA1D time-dependently whereas total protein showed little change. Untreated LNCaP were unresponsive to depolarising high K+/Bay K (to activate CaV1.3); moreover, currents were rarely detected. ADT or ENZ-treated LNCaP exhibited nifedipine-sensitive Ca2+-transients; ADT-treated LNCaP exhibited mibefradil-sensitive or, occasionally, nifedipine-sensitive inward currents. CACNA1D knockdown reduced the subpopulation of treated-LNCaP with CaV1.3 activity. VCaP displayed nifedipine-sensitive high K+/Bay K transients (responding subpopulation was increased by ENZ), and Ni2+-sensitive currents. Hormone therapy enables depolarization/Bay K-evoked Ca2+-transients and detection of CaV1.3 and CaV3.2 currents. Physiological and genomic CACNA1D/CaV1.3 mechanisms are likely active during hormone therapy—their modulation may offer therapeutic advantage.
Fascicle dynamics of the tibialis anterior muscle reflect whole-body walking economy
Authors: Kwak Samuel T. , Chang Young-Hui
Published: March 2023

Humans can inherently adapt their gait pattern in a way that minimizes the metabolic cost of transport, or walking economy, within a few steps, which is faster than any known direct physiological sensor of metabolic energy. Instead, walking economy may be indirectly sensed through mechanoreceptors that correlate with the metabolic cost per step to make such gait adaptations. We tested whether velocity feedback from tibialis anterior (TA) muscle fascicles during the early stance phase of walking could potentially act to indirectly sense walking economy. As participants walked within a range of steady-state speeds and step frequencies, we observed that TA fascicles lengthen on almost every step. Moreover, the average peak fascicle velocity experienced during lengthening reflected the metabolic cost of transport of the given walking condition. We observed that the peak TA muscle activation occurred earlier than could be explained by a short latency reflex response. The activation of the TA muscle just prior to heel strike may serve as a prediction of the magnitude of the ground collision and the associated energy exchange. In this scenario, any unexpected length change experienced by the TA fascicle would serve as an error signal to the nervous system and provide additional information about energy lost per step. Our work helps provide a biomechanical framework to understand the possible neural mechanisms underlying the rapid optimization of walking economy.
Sex-differences in prostaglandin signaling: a semi-systematic review and characterization of PTGDS expression in human sensory neurons
Authors: Shen Breanna Q. , Sankaranarayanan Ishwarya , Price Theodore J. , Tavares-Ferreira Diana
Published: March 2023

There is increasing evidence of sex differences in underlying mechanisms causing pain in preclinical models, and in clinical populations. There are also important disconnects between clinical pain populations and the way preclinical pain studies are conducted. For instance, osteoarthritis pain more frequently affects women, but most preclinical studies have been conducted using males in animal models. The most widely used painkillers, nonsteroidal anti-inflammatory drugs (NSAIDs), act on the prostaglandin pathway by inhibiting cyclooxygenase (COX) enzymes. The purpose of this study was to analyze the preclinical and clinical literature on the role of prostaglandins and COX in inflammation and pain. We aimed to specifically identify studies that used both sexes and investigate whether any sex-differences in the action of prostaglandins and COX inhibition had been reported, either in clinical or preclinical studies. We conducted a PubMed search and identified 369 preclinical studies and 100 clinical studies that matched our inclusion/exclusion criteria. Our analysis shows that only 17% of preclinical studies on prostaglandins used both sexes and, out of those, only 19% analyzed or reported data separated by sex. In contrast, 79% of the clinical studies analyzed used both sexes. However, only 6% of those reported data separated by sex. Interestingly, 14 out of 15 preclinical studies and 5 out of 6 clinical studies that analyzed data separated by sex have identified sex-differences. This builds on the increasing evidence of sex-differences in prostaglandin signaling and the importance of sex as a biological variable in data analysis. The preclinical literature identifies a sex difference in prostaglandin D2 synthase (PTGDS) expression where it is higher in female than in male rodents in the nervous system. We experimentally validated that PTGDS expression is higher in female human dorsal root ganglia (DRG) neurons recovered from organ donors. Our semi-systematic literature review reveals a need for continued inclusivity of both male and female animals in prostaglandins studies and data analysis separated by sex in preclinical and clinical studies. Our finding of sex-differences in neuronal PTGDS expression in humans exemplifies the need for a more comprehensive understanding of how the prostaglandin system functions in the DRG in rodents and humans.
Quartile coefficient of variation is more robust than CV for traits calculated as a ratio
Authors: Botta-Dukát Zoltán
Published: March 2023

Comparing within-species variations of traits can be used in testing ecological theories. In these comparisons, it is useful to remove the effect of the difference in mean trait values, therefore measures of relative variation, most often the coefficient of variation (CV), are used. The studied traits are often calculated as the ratio of the size or mass of two organs: e.g. specific leaf area (SLA) is the ratio of leaf size and leaf mass. Often the inverse of these ratios is also meaningful; for example, the inverse of SLA is often referred to as LMA (leaf mass per area). Relative variation of a trait and its inverse should not considerably differ. However, it is illustrated that using the coefficient of variation may result in differences that could influence the interpretation, especially if there are outlier trait values. The alternative way for estimating CV from the standard deviation of log-transformed data assuming log-normal distribution and Kirkwood’s geometric coefficient of variation free from this problem, but they proved to be sensitive to outlier values. Quartile coefficient of variation performed best in the tests: it gives the same value for a trait and its inverse and it is not sensitive to outliers.
NTSR1 glycosylation and MMP dependent cleavage generate three distinct forms of the protein
Authors: Libanje Fotine , Delille Raphael , Young Pamela A , Rolland Sylvie , Meyer-Losic Florence , Lewkowicz Elodie , Klinz Stephan
Published: March 2023

NTSR1 abnormal expression by cancer cells makes it a strategic target for antitumoral therapies, such as compounds that use NTSR1 binding probes to deliver cytotoxic agents to tumor cells. Success of these therapies relies on NTSR1 protein availability and accessibility; therefore, understanding the protein’s biology is crucial. We studied NTSR1 protein in exogenously and endogenously expressing non-tumoral and tumoral cells. We found NTSR1 to be expressed as three distinct protein forms: the NTSR1-high form, a glycosylated protein; the NTSR1-low form, a N-terminally cleaved and de-glycosylated protein; and the NTSR1-LP protein with the MW size predicted by its NTSR1 amino acid sequence. We show that the NTSR1-high form is cleaved by MMPs to generate the NTSR1-low form, a process that is promoted by the Neurotensin (NTS) ligand. In addition, NTS induced the internalization of plasma membrane localized NTSR1 and degradation of NTSR1-low form via the proteasome. Importantly, we found NTSR1-low form to be the most abundant form in the tumoral cells and in PDAC Patient Derived Xenograft, demonstrating its physiopathological relevance. Altogether, our work provides important technical and experimental tools as well as new crucial insights into NTSR1 protein biology that are required to develop clinically relevant NTSR1 targeting anti-tumoral therapies.
Copper phenanthroline for selective electrochemical CO2reduction on carbon paper
Authors: Du Jiehao , Cheng Banggui , Jiang Long , Han Zhiji
Published: March 2023

A simple system to control the selectivities of C2products in electrochemical CO2reduction with copper phenanthroline on carbon paper.
Carnauba wax-based sustainable coatings for prolonging postharvest shelf-life of citrus fruits
Authors: Devi L. Susmita , Mukherjee Avik , Dutta Debjani , Kumar Santosh
Published: March 2023

Citrus fruits are extremely popular for their rich nutritional attributes and health benefits, but they are perishable in nature, and growers and suppliers often face financial losses due to rapid postharvest decay in the fruits.
Integrated transcriptomics, proteomics and metabolomics to identify biomarkers of astragaloside IV against cerebral ischemic injury in rats
Authors: Wei Xiaoyu , He Yu , Wan Haitong , Yin Junjun , Lin Bingying , Ding Zhishan , Yang Jiehong , Zhou Huifen
Published: March 2023

Based on transcriptomic, proteomic, and metabolomic analyses, we developed an strategy to explore the key targets and mechanisms of Astragaloside IV treatment for cerebral ischemia in rats to obtain a compound–reaction–enzyme–gene network.
Engineering probiotics-derived membrane vesicles for encapsulating fucoxanthin: evaluation of stability, bioavailability, and biosafety
Authors: Liang Duo , Liu Chenyue , Li Jiaxuan , Li Yu , Li Jiashu , Tan Mingqian , Su Wentao
Published: March 2023

Schematic diagram of the fabrication of membrane vesicles for improving the stability and enhancing the absorption and oral biosafety of fucoxanthin.
Evidence of half-metallicity at the BiFeO3(001) surface
Authors: Jena Soumyasree , Datta Sanjoy
Published: March 2023

Evidence of half-metallicity at the BiFeO3 (001) surface has been found. Half-metals are considered to be one of the most promising candidate for efficient spin-injection and detection processes in spintronic devices.
Modifying flexible polymer films towards superhydrophobicity and superoleophobicity by utilizing water-based nanohybrid coatings
Authors: Krasanakis Fanourios , Chatzaki Thaleia-Michaela , Chrissopoulou Kiriaki , Anastasiadis Spiros H.
Published: March 2023

Waterborne nanocomposite coatings consisting of a low surface energy matrix in conjunction with appropriate nanoparticles were developed to be deposited onto flexible polyethylene films to modify them into superhydrophobic and even superoleophobic.
Phenylboronic acid-modified polyethyleneimine assisted neutral polysaccharide detection and weight-resolution analysis with a nanopipette
Authors: Xie Wanyi , He Shixuan , Fang Shaoxi , Tian Rong , Liang Liyuan , Wang Deqiang
Published: March 2023

A high-charge polymer molecule PEI-oBA is introduced to assisted low molecular weight neutral dextran detection based on nanopipette technology.
Acetylene bridged alkoxyphenanthrene and triarylamine-based triads for low threshold voltage with high mobility OFETs
Authors: Balambiga Balu , Devibala Panneerselvam , Harshini Deivendran , Imran Predhanekar Mohamed , Nagarajan Samuthira
Published: March 2023

New phenanthrene and triarylamine-based organic semiconductors with D′–π–D–π–D′ architecture were designed and synthesized for OFETs, the fabricated BGTC devices exhibited μh and Ion/off up to 3.5 cm2 V−1 s−1 and 108 and the lowest Vth up to −3 V, respectively.
Quantitative analysis of phenanthrene in soil by fluorescence spectroscopy coupled with the CARS-PLS model
Authors: Li Haonan , Li Maogang , Tang Hongsheng , Li Hua , Zhang Tianlong , Yang Xiao-Feng
Published: March 2023

Fluorescence spectroscopy coupled with CARS-PLS model is successfully used for the rapid quantitative analysis of phenanthrene in soil.
Visible light antibacterial potential of cement mortar incorporating Cu-ZnO/g-C3N4 nanocomposites
Authors: Liu Xiaomin , Yang Zhengxian , Li Kang , Briseghella Bruno , Marano Giuseppe Carlo , Xu Jiankun
Published: March 2023

A hybrid Cu-ZnO/g-C3N4 nanocomposite was synthesized and introduced to fabricate photocatalytic cement mortar whose bactericidal activity was investigated under visible light.