bluuebunny/crossref_metadata_2025 huggingface dataset:
The prospects for European aerospace transporters - Part 1: The derivation of a first order parametric method for estimating the development cost of aerospace transporters
Authors: Ashford D. M. , Collins P. Q.
Published: March 2023

Manned spacecraft cost typically ten times as much to develop as advanced technology prototype aeroplanes of similar weight. For example, the Hermes spaceplane, which is designed to be launched into orbit by the expendable Ariane 5, has an estimated development cost of $4 billion, which is about ten times greater than the cost of the Experimental Aircraft Programme (EAP) demonstrator of the European Fighter Aircraft ($350 million). The Hermes spaceplane and the EAP are of comparable size and weight and both use very advanced technology. The EAP is already more mature than Hermes would become because, although the EAP is only a prototype, it has made more flights than are planned for Hermes over its entire operational career.

This part of the paper attempts to identify the factors which explain this difference in cost and then to determine which of them would apply to fully reusable, piloted, aeroplane-like launchers, i.e. aerospace transporters.
Sycomores concept
Authors: Dulck J. F. , Larregola R. , Mariet G. , Rouffet D.
Published: March 2023

Most organisations predict that the expansion of satellite applications to new areas, such as land mobile communications, will be in a rapid worldwide growth phase up to the end of the century. The geographical and geometrical link properties along with the economic aspects (with the projected saturation of the frequency allocation), have led communications services to consider non-conventional orbits for the near future. This paper presents an analysis of the fundamental problems and a statement on the short-term technical solutions within the particular framework of a general land mobile communication mission. The results of these efforts led the authors to propose the Sycomores concept, which is at least a twin satellite system located on particular inclined elliptical geosynchronous orbits.
Fracture analysis of complex shaped structures by numerical and experimental methods
Authors: Marchetti M. , La Barbera A. , Morganti F.
Published: March 2023

The problem of fracture characterisation of geometrically complex structures is considered. Numerical and experimental strategies are used to evaluate stress intensity factors and elastic fields for cracked thin shell and plate structures. Theoretical analyses, using different order theories, are also performed in order to evaluate stress and energy distributions in the neighbourhood of the crack tip. A geometrically complex strut component is analysed by using a ‘p-convergent’ finite element code based on hierarchic elements and on the high degree of approximating functions. Actual fracture modes, for different crack locations, have been singled out and the elastic fields are compared to those referring to cracked plate and shell structures. An experimental investigation, using the optical method of caustics, has been also performed and stress intensity factors for several crack configurations have been calculated. The numerical investigations have shown the ability of the p-version finite element method to provide accurate computation of local stress values and to quote the convergence of the numerical calculations. The caustics method has confirmed its accuracy for evaluating stress intensity factors, even for complex structures.
Counterinsurgency Tactics, Rebel Grievances, and Who Keeps Fighting
Authors: HUFF CONNOR
Published: March 2023

How do government counterinsurgency tactics shape the behavior of the rebels they are combating? This letter builds upon foundational theories of civil war to argue that within-conflict government actions can further increase rebels’ levels of grievances. This increases the likelihood rebels continue fighting as conflicts unfold. I test the argument using newly compiled individual-level data on over 1,700 members of the Irish Volunteers and Irish Citizen Army who participated in the 1916 Easter Rising. Rebels varied in whether they were interned after the uprising. I show that rebels who were interned were more likely to fight throughout the entire Irish War of Independence. Qualitative evidence corroborates the contention that internment increased rebels’ levels of grievances. The letter elucidates how within-conflict events shape rebel behavior, by documenting how the tactics governments employ as they fight can shape the subsequent actions of the rebels they are combating.
VITELLIUS AND THE SHIELD OF MINERVA
Authors: Connolly Serena
Published: March 2023

In 69 ce, the emperor Vitellius presented to dinner guests his ‘Shield of Minerva’, a platter filled with pike livers, pheasant and peacock brains, flamingo tongues, and lamprey milt. Just as Vitellius’ passion for food has been distorted into gluttony, so the Shield of Minerva has been misrepresented as a culinary abomination and the worst of the emperor's excesses. Modern scholarly reception of the Shield owes much to hostile ancient sources, but is also influenced by some modern culinary preferences. Critical reading of our sources reveals the dish as a mix of ingredients carefully chosen for their gustatory and visual appeal and for their political and military symbolism. Vitellius’ association of the platter with Minerva evokes her status not only as a martial deity, but also as a goddess of craft. The Shield of Minerva is revealed to be an intellectual exercise, not a symbol of gluttonous self-indulgence.
Greek literature
Authors: Heath Malcolm
Published: March 2023

Stephen Halliwell has, at last, completed his three-volume verse translation of Aristophanes. The first instalment, published in 1997, covered Aristophanes’ ‘longest play, Birds, his sexiest play, Lysistrata, and two works from very near the end of his career, Assembly-Women and Wealth’. Geoffrey Arnott's review of that first volume was positive: ‘H.'s style is lively, modern, and generally effective, closer perhaps in its presentation of the complexities of Aristophanic detail and reference than most of his rivals…He is virtually always accurate without being over-literal, and far more often graphically idiomatic than flat.’ Arnott's assessment was generally favourable, although he did identify some imperfections: ‘errors in detail are few and far between (Birds 244, “marshy greens”, not “rolling hills”; 266, “like a stone curlew”, not “with a waterfall of sound”; Eccl. 1092, βολβoί not “onions”; Plut. 192, μάζα not “bread”)’, and Halliwell ‘would have benefited from having his translation of Birds vetted by an ornithologist, who would have removed the phantasmagorical blue thrush (979), and turned the moorhen (304), siskins (1079), and curlews (1140) into gallinule, chaffinches, and stone curlews’. I confess that I could not possibly have managed that menagerie myself; Arnott, of course, was an accomplished ornithologist. Halliwell's original plan was to deal with ‘the “political” plays from the 420s, Acharnians, Knights, Wasps, and Peace’ in the second instalment, and ‘the comedies on more “cultural” themes, Clouds, Women at the Thesmophoria, and Frogs’ in the third. In the event, the sequence of ‘cultural’ and ‘political’ volumes was recast in biblical form: ‘the last shall be first and the first shall be last’ (Matthew 20.16). Or, perhaps, vice versa. The format for each volume is, at any rate, consistent: each volume has a substantial introduction, with a bibliography and brief chronology; and each play has its own introduction, together with fourteen or so pages of explanatory notes. As a sample of Halliwell's translation, consider (for example) this taster from Peace (996–1,014):Blend all us Greeks,As we once used to be,In an essence of friendship, and mix our mindsIn a milder spirit of sympathy.Allow our market to teem with goods:From Megara bring us heads of garlic,Early cucumbers, apples, pomegranates,Fancy cloaks for slaves to wear.From Boiotian traders we'd like to seeGeese, ducks, wood-pigeons, and wrens,As well as baskets of Kopaic eels.Then may we all crowd round these basketsAnd buying our food get into a jostleWith Morychos, Teleas, Glauketes,And numerous other gluttons. And nextMay Melanthios come to the market too late,When the eels are all sold: let him ululate,Then sing a solo from his Medea,‘I'm doomed, I'm doomed, now quite bereftOf a female embedded in beetroot’.
Greek history
Authors: Vlassopoulos Kostas
Published: March 2023

I commence this review with a number of important works in Greek social history. As I commented in my last review for this journal, the study of labour is among the biggest holes in current research in Greek history. An important contribution towards filling this gap is the Cultural History of Work in Antiquity, edited by Ephraim Lytle. The volume gives an excellent overview of how work is represented and discussed in both literary and archaeological sources; at the same time, it situates work and workers within four important contexts: the structures of ancient economies and the level of trade and specialization determined demand in urban and rural labour; the changing form of workplaces determined the division of labour among workers; different forms of work developed highly divergent workplace cultures; finally, practices and organizations for the transmission of skills and knowledge were of critical importance. Work and workers are then placed within wider contexts: chapters explore the role of mobility in ancient labour markets, and how political communities and attitudes about different forms of work affected workers. Finally, work is profitably juxtaposed to leisure practices and ideas. Perhaps the strongest point of most chapters is their attention to regional diversity and historical change: the volume sets the groundwork for ultimately producing a dynamic narrative of the history of work in antiquity.
Roman History
Authors: Corke-Webster James
Published: March 2023

Do you want to hear something worth knowing? If so, you're in luck, because Pliny the Elder has 20,000 such nuggets ready for your delectation. Even better, one of the elder statesmen of Roman history, Richard Saller, has provided a fresh study of them in his new book, Pliny's Roman Economy. Saller is famous for publications that have painted in broad brush strokes the landscape of Roman economic and social history as we now understand it. Here, instead, he offers a brief, focused study of a single author, albeit one whose Natural History is of extraordinarily ambitious scope. Published in ‘The Princeton Economic History of the Western World’ series, this is a book for both classicists and economic historians with a focused aim: to use Pliny to intervene in the long-standing debate over whether the Roman imperial economy enjoyed sustainable growth in the first two centuries ce (behind which lurks, as Saller notes, the more existential question as to whether the oppression of the Roman imperial project came with benefits). This question arises from a controversial methodological contention – that scholars’ efforts to develop sophisticated proxies to enable quantitative assessment of ancient economic growth (now largely associated with New Institutional Economics) have so far failed, and thus that we should return, at least in part, to more traditional use of literary sources: ‘at this point none [of those proxies] is reliable enough to justify neglecting our aristocratic authors’ (3). Pliny is particularly interesting here because eighteenth-century encyclopaedias have been seen (in part by the series editor, Joel Mokyr) as part of a culture of innovation that in turn fed the pronounced economic growth of that period.
General
Authors: Petrovic Andrej
Published: March 2023

Since we are globally more or less saved from a disease, if perhaps not quite yet from the threat of a global conflict (the transition from a pandemic to a large-scale war is never easy), I start with two books that deal with deliverance, the first one deliverance from danger, the second book with the deliverance from death.
NEUTRAL ARMS TRANSFERS AND THE RUSSIAN INVASION OF UKRAINE
Authors: Clancy Pearce
Published: March 2023

Since the beginning of the Russian invasion of Ukraine in February 2022, numerous Western States have supplied Ukraine with arms, munitions and war material, in ostensible breach of their obligations as neutral, non-participating States. States have failed to provide any legal explanation for such transfers, leaving the task to scholars and commentators to provide legal argumentation as to the compatibility of arms transfers to victims of aggression with neutral duties. This article analyses and seeks to evaluate these arguments in favour of ‘qualified neutrality’ and assess which of the proposed grounds, if any, are the most compelling.
Medical Legitimacy: Childbirth, Pluralism, and Professionalization in Nigeria's Faith-Based Aladura Birthing Homes
Authors: Williams Ogechukwu E.
Published: March 2023

In the wake of the Aladura (prayer people) religious movement of the late 1920s, a site of childbirth that relied primarily on faith healing emerged in Nigeria under the Christ Apostolic Church (CAC). This practice of faith-based delivery remained informal until 1959 when it evolved into a permanent structure with a professional guild of midwives, codified practices, and trained personnel. This article explores the advent of CAC's faith-based maternity practice, notably its faith home midwifery school, and how the faith home transformed its identity from the informal realms of religious healing to a recognized religious entity that offered primary maternity care based on the principles of faith healing. By examining the professionalization of Aladura faith homes, I highlight questions of legitimacy allocation in postcolonial Africa and how CAC navigated this process by courting legitimacy from state-backed institutions and sociocultural frameworks.
Effects of early-life environment and adulthood SES on cognitive change in a multiethnic cohort
Authors: Meyer Oanh L. , Harrati Amal , Gavett Brandon E. , Farias Sarah T. , Whitmer Rachel A. , Widaman Keith , Hoang Victoria , Tobias Michele , Mungas Dan
Published: March 2023

Objectives:

Early-life socioeconomic status (SES) and adversity are associated with late-life cognition and risk of dementia. We examined the association between early-life SES and adversity and late-life cross-sectional cognitive outcomes as well as global cognitive decline, hypothesizing that adulthood SES would mediate these associations.

Methods:

Our sample (N = 837) was a racially and ethnically diverse cohort of non-Hispanic/Latino White (48%), Black (27%), and Hispanic/Latino (19%) participants from Northern California. Participant addresses were geocoded to the level of the census tract, and US Census Tract 2010 variables (e.g., percent with high school diploma) were extracted and combined to create a neighborhood SES composite. We used multilevel latent variable models to estimate early-life (e.g., parental education, whether participant ever went hungry) and adult (participant’s education, main occupation) SES factors and their associations with cross-sectional and longitudinal cognitive outcomes of episodic memory, semantic memory, executive function, and spatial ability.

Results:

Child and adult factors were strongly related to domain-specific cognitive intercepts (0.20–0.48 SD per SD of SES factor); in contrast, SES factors were not related to global cognitive change (0.001–0.01 SD per year per SD of SES factor). Adulthood SES mediated a large percentage (68–75%) of the total early-life effect on cognition.

Conclusions:

Early-life sociocontextual factors are more strongly associated with cross-sectional late-life cognitive performance compared to cognitive change; this effect is largely mediated through associations with adulthood SES.
Irreversible and Large‐Scale Heavy Metal Pollution Arising From Increased Damming and Untreated Water Reuse in the Nile Delta
Authors: Abotalib Abotalib Z. , Abdelhady Ahmed A. , Heggy Essam , Salem Salem G. , Ismail Esam , Ali Ahmed , Khalil Mahmoud M.
Published: March 2023

Egypt observes one of the highest water budget deficits in Africa that is mainly compensated by intensive reuse of untreated agricultural drainage water in the Nile Delta. The implications of untreated water reuse on increasing soil pollution levels remain poorly characterized; however, a large‐scale pollution can compromise crop production and water quality. To address this deficiency, we evaluate the level of heavy metal pollution in the Nile Delta, identify its sources and explore the implications of damming on heavy metal concentration using integrated pollution indicators and statistical modeling. Pollution indicators show moderate to very high contamination by Pb, Ni, Cr, Cd, Cu, and Zn, with unprecedented Cd levels in the sediments (up to 72.0 ppm) and a northward increase in pollution levels. Statistical modeling and historical datasets reveal the association of Cd and Fe on both Nile branches and the clustering of Pb, Ni, Cu, Zn and Cr, which attribute the heavy metal concentrations to the cumulative addition of untreated agricultural drainage water (9.5 BCM/yr) and wastewater. These processes introduced an accelerated pollution in the Nile Delta system. Though, conservation measures are crucial to reverse this degradation, yet the increasingly engineered Nile flow, the low gradient of the delta and the active silting impede heavy metal flushing causing irreversible pollution. Our findings alarm future increase in heavy metal pollution in response to increased untreated drainage water reuse to mitigate the impacts of ongoing upstream damming and call for implementing international cooperative agreements for integrated water management along the Nile River.
Shear Velocity Evidence of Upper Crustal Magma Storage Beneath Valles Caldera
Authors: Wilgus Justin , Schmandt Brandon , Maguire Ross , Jiang Chengxin , Chaput Julien
Published: March 2023

Valles Caldera was formed by large rhyolitic eruptions at ∼1.6 and 1.23 Ma and it hosts post‐caldera rhyolitic deposits as young as ∼69 ka, but the contemporary state of the magmatic system is unclear. Local seismicity beneath Valles Caldera is rare and shear‐velocity (Vs) structure has not been previously imaged. Here, we present the first local Vs tomography beneath Valles Caldera using ambient noise Rayleigh dispersion from a ∼71 km transect of nodal seismographs with mean spacing of ∼750 m. An ∼6 km wide low‐Vs anomaly (Vs < 2.1 km/s) is located at ∼3–10 km depth within the 1.23 Ma caldera's ring fracture. Assuming magma in textural equilibrium, the new tomography suggests that melt fractions up to ∼17%–22% may be present within the upper crustal depth range where previously erupted rhyolites were stored.
A Global Quantification of the Physical Processes Leading to Near‐Surface Cold Extremes
Authors: Röthlisberger Matthias , Papritz Lukas
Published: March 2023

Kinematic backward trajectories are used to globally quantify the contributions of temperature advection, adiabatic compression and diabatic processes to near‐surface temperature anomalies (hereafter ) during the coldest day of each year (TN1day events) based on ERA5. Diabatic cooling dominates TN1day anomalies in the climatologically coldest regions, while advection forms TN1day anomalies over most ocean regions. Over most extratropical land masses, TN1day anomalies arise from a combination of both processes. The mean age and formation distance of TN1day anomalies vary strongly in space, from one to 8 days, and 500–5,500 km, respectively. Five distinct types of TN1day events are identified from these physical and spatio‐temporal characteristics, and their geographical occurrence is investigated. Furthermore, advective, adiabatic and diabatic contributions typically cancel each other partially, but less so for the most intense TN1day events, which occur when the atmosphere's ability to dampen near‐surface temperature anomalies is limited.
Algorithm Stability and the Long‐Term Geospace Data Record From TIMED/SABER
Authors: Mlynczak Martin G. , Marshall B. Thomas , Garcia Rolando R. , Hunt Linda , Yue Jia , Harvey V. Lynn , Lopez‐Puertas Manuel , Mertens Chris , Russell James
Published: March 2023

The ability of satellite instruments to accurately observe long‐term changes in atmospheric temperature depends on many factors including the absolute accuracy of the measurement, the stability of the calibration of the instrument, the stability of the satellite orbit, and the stability of the numerical algorithm that produces the temperature data. We present an example of algorithm instability recently discovered in the temperature data set from the SABER instrument on the NASA TIMED satellite. The instability resulted in derived temperatures that were substantially colder than anticipated from mid‐December 2019 to mid‐2022. This algorithm‐induced change in temperature over 1 to 2 years corresponded to the expected temperature change over several decades from increasing anthropogenic CO2. This paper highlights the importance of algorithm stability in developing Geospace Data Records (GDRs) for Earth’s mesosphere and lower thermosphere. A corrected version (Version 2.08) of the temperatures from SABER is described.
Insights Into the Dynamics of Vegetated Alternate Bars by Means of Flume Experiments
Authors: Calvani G. , Francalanci S. , Solari L.
Published: March 2023

Alternate bars are bedforms recognizable in straight or weakly curved channels as a result of riverbed instability. The length and height of alternate bars scale with the river width and the water depth, respectively. During low water stages, alternate bars become exposed and can be colonized by riparian vegetation. The effects of established plants on the morphodynamics of alternate bars have been poorly investigated. In this work, we focus on the effects induced by rigid vegetation on the dynamics and morphology of previously developed alternate bars in a straight channel by means of flume experiments. We investigate three different spatial densities of plants to reproduce scenarios of vegetation establishment. The results illustrate that vegetation alters both the altimetric and planimetric characteristics of bar patterns. In particular, as compared to bare‐bed bars, vegetated bars have a higher wave amplitude and scour, and this effect becomes stronger with plant density. Moreover, they exhibit decreasing wavenumbers according to vegetation density. A comparison with previous fundamental work for the planimetric instability of straight channels with bare‐bed alternate bars, suggests that the established vegetated bars may promote the transition to river meandering.
Windmapper: An Efficient Wind Downscaling Method for Hydrological Models
Authors: Marsh Christopher B. , Vionnet Vincent , Pomeroy John W.
Published: March 2023

Estimates of near‐surface wind speed and direction are key meteorological components for predicting many surface hydrometeorological processes that influence critical aspects of hydrological and biological systems. However, observations of near‐surface wind are typically spatially sparse. The use of these sparse wind fields to force distributed models, such as hydrological models, is greatly complicated in complex terrain, such as mountain headwaters basins. In these regions, wind flows are heavily impacted by overlapping influences of terrain at different scales. This can have a great impact on calculations of evapotranspiration, snowmelt, and blowing snow transport and sublimation. The use of high‐resolution atmospheric models allows for numerical weather prediction (NWP) model outputs to be dynamically downscaled. However, the computation burden for large spatial extents and long periods of time often precludes their use. Here, a wind‐library approach is presented to aid in downscaling NWP outputs and terrain‐correcting spatially interpolated observations. This approach preserves important spatial characteristics of the flow field at a fraction of the computational costs of even the simplest high‐resolution atmospheric models. This approach improves on previous implementations by: scaling to large spatial extents O(1M km2); approximating lee‐side effects; and fully automating the creation of the wind library. Overall, this approach was shown to have a third quartile RMSE of 1.8  and a third quartile RMSE of 58.2° versus a standalone diagnostic windflow model. The wind velocity estimates versus observations were better than existing empirical terrain‐based estimates and computational savings were approximately 100‐fold versus the diagnostic model.
Exploring the Optimal Location of Pumps as Turbines Within Branched Irrigation Networks by Global Optimization
Authors: Morani M. C. , Crespo Chacón M. , Garcia Morillo J. , McNabola A. , Fecarotta O.
Published: March 2023

In this study a new procedure to address the optimization of the location and selection of pumps as turbines (PATs) within irrigation networks is presented in order to reduce network pressure and recover energy. The proposed procedure consists of two steps: in the first step the optimization of the location of devices is performed, then the optimal selection and regulation is investigated in the second step. Two new mixed integer non‐linear models have been developed and a global optimization solver has been employed to perform both optimization procedures. The procedure has been tested on a real irrigation network in Spain. The entire 2015 irrigation season has been used to properly model the water demand within the system. According to the results, the optimal solution consists of 5 PATs, installed in the middle region of the system. The investment cost has been estimated as 169,278 € with a payback period of almost 4.2 irrigation seasons. According to the solution, the effective amount of produced energy is equal to 289 MWh if the system is properly regulated and the pressure exceeding the minimum requirements is exploited to produce energy. Compared to other studies in literature focused on irrigated agriculture, the number of PATs is not fixed but rather it results from the maximization of the energy recovery and the minimization of capital costs, simultaneously. Moreover, the proposed procedure relies on a deterministic approach, achieving promising results in terms of accuracy.
Marauding Moons Spell Disaster for Some Planets
Authors: Kornei Katherine
Published: March 2023

In solar systems beyond our own, some moons might eventually collide with their host planets, new simulations suggest.
An old model with new insights: endogenous retroviruses drive the evolvement toward ASD susceptibility and hijack transcription machinery during development
Authors: Lin Chia-Wen , Ellegood Jacob , Tamada Kota , Miura Ikuo , Konda Mikiko , Takeshita Kozue , Atarashi Koji , Lerch Jason P. , Wakana Shigeharu , McHugh Thomas J. , Takumi Toru
Published: March 2023

The BTBR T+Itpr3tf/J (BTBR/J) strain is one of the most valid models of idiopathic autism, serving as a potent forward genetics tool to dissect the complexity of autism. We found that a sister strain with an intact corpus callosum, BTBR TF/ArtRbrc (BTBR/R), showed more prominent autism core symptoms but moderate ultrasonic communication/normal hippocampus-dependent memory, which may mimic autism in the high functioning spectrum. Intriguingly, disturbed epigenetic silencing mechanism leads to hyperactive endogenous retrovirus (ERV), a mobile genetic element of ancient retroviral infection, which increases de novo copy number variation (CNV) formation in the two BTBR strains. This feature makes the BTBR strain a still evolving multiple-loci model toward higher ASD susceptibility. Furthermore, active ERV, analogous to virus infection, evades the integrated stress response (ISR) of host defense and hijacks the transcriptional machinery during embryonic development in the BTBR strains. These results suggest dual roles of ERV in the pathogenesis of ASD, driving host genome evolution at a long-term scale and managing cellular pathways in response to viral infection, which has immediate effects on embryonic development. The wild-type Draxin expression in BTBR/R also makes this substrain a more precise model to investigate the core etiology of autism without the interference of impaired forebrain bundles as in BTBR/J.
Emerging phagocytosis checkpoints in cancer immunotherapy
Authors: Liu Yu’e , Wang Yanjin , Yang Yanrong , Weng Linjun , Wu Qi , Zhang Jin , Zhao Pengcheng , Fang Lan , Shi Yufeng , Wang Ping
Published: March 2023

Cancer immunotherapy, mainly including immune checkpoints-targeted therapy and the adoptive transfer of engineered immune cells, has revolutionized the oncology landscape as it utilizes patients’ own immune systems in combating the cancer cells. Cancer cells escape immune surveillance by hijacking the corresponding inhibitory pathways via overexpressing checkpoint genes. Phagocytosis checkpoints, such as CD47, CD24, MHC-I, PD-L1, STC-1 and GD2, have emerged as essential checkpoints for cancer immunotherapy by functioning as “don’t eat me” signals or interacting with “eat me” signals to suppress immune responses. Phagocytosis checkpoints link innate immunity and adaptive immunity in cancer immunotherapy. Genetic ablation of these phagocytosis checkpoints, as well as blockade of their signaling pathways, robustly augments phagocytosis and reduces tumor size. Among all phagocytosis checkpoints, CD47 is the most thoroughly studied and has emerged as a rising star among targets for cancer treatment. CD47-targeting antibodies and inhibitors have been investigated in various preclinical and clinical trials. However, anemia and thrombocytopenia appear to be formidable challenges since CD47 is ubiquitously expressed on erythrocytes. Here, we review the reported phagocytosis checkpoints by discussing their mechanisms and functions in cancer immunotherapy, highlight clinical progress in targeting these checkpoints and discuss challenges and potential solutions to smooth the way for combination immunotherapeutic strategies that involve both innate and adaptive immune responses.
Non-canonical functions of SNAIL drive context-specific cancer progression
Authors: Paul Mariel C. , Schneeweis Christian , Falcomatà Chiara , Shan Chuan , Rossmeisl Daniel , Koutsouli Stella , Klement Christine , Zukowska Magdalena , Widholz Sebastian A. , Jesinghaus Moritz , Heuermann Konstanze K. , Engleitner Thomas , Seidler Barbara , Sleiman Katia , Steiger Katja , Tschurtschenthaler Markus , Walter Benjamin , Weidemann Sören A. , Pietsch Regina , Schnieke Angelika , Schmid Roland M. , Robles Maria S. , Andrieux Geoffroy , Boerries Melanie , Rad Roland , Schneider Günter , Saur Dieter
Published: March 2023

SNAIL is a key transcriptional regulator in embryonic development and cancer. Its effects in physiology and disease are believed to be linked to its role as a master regulator of epithelial-to-mesenchymal transition (EMT). Here, we report EMT-independent oncogenic SNAIL functions in cancer. Using genetic models, we systematically interrogated SNAIL effects in various oncogenic backgrounds and tissue types. SNAIL-related phenotypes displayed remarkable tissue- and genetic context-dependencies, ranging from protective effects as observed in KRAS- or WNT-driven intestinal cancers, to dramatic acceleration of tumorigenesis, as shown in KRAS-induced pancreatic cancer. Unexpectedly, SNAIL-driven oncogenesis was not associated with E-cadherin downregulation or induction of an overt EMT program. Instead, we show that SNAIL induces bypass of senescence and cell cycle progression through p16INK4A-independent inactivation of the Retinoblastoma (RB)-restriction checkpoint. Collectively, our work identifies non-canonical EMT-independent functions of SNAIL and unravel its complex context-dependent role in cancer.
Engineering zero modes in transformable mechanical metamaterials
Authors: Hu Zhou , Wei Zhibo , Wang Kun , Chen Yan , Zhu Rui , Huang Guoliang , Hu Gengkai
Published: March 2023

In the field of flexible metamaterial design, harnessing zero modes plays a key part in enabling reconfigurable elastic properties of the metamaterial with unconventional characteristics. However, only quantitative enhancement of certain properties succeeds in most cases rather than qualitative transformation of the metamaterials’ states or/and functionalities, due to the lack of systematic designs on the corresponding zero modes. Here, we propose a 3D metamaterial with engineered zero modes, and experimentally demonstrate its transformable static and dynamic properties. All seven types of extremal metamaterials ranging from null-mode (solid state) to hexa-mode (near-gaseous state) are reported to be reversibly transformed from one state to another, which is verified by the 3D-printed Thermoplastic Polyurethanes prototypes. Tunable wave manipulations are further investigated in 1D-, 2D- and 3D-systems. Our work sheds lights on the design of flexible mechanical metamaterials, which can be potentially extended from the mechanical to the electro-magnetite, the thermal or other types.
Structural basis of peptide recognition and activation of endothelin receptors
Authors: Ji Yujie , Duan Jia , Yuan Qingning , He Xinheng , Yang Gong , Zhu Shengnan , Wu Kai , Hu Wen , Gao Tianyu , Cheng Xi , Jiang Hualiang , Eric Xu H. , Jiang Yi
Published: March 2023

Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes—endothelin receptor A (ETAR) and B (ETBR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETAR and ETBR bound to ET-1 and ETBR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes.
Distinct roles of Arabidopsis ORC1 proteins in DNA replication and heterochromatic H3K27me1 deposition
Authors: Vergara Zaida , Gomez María S. , Desvoyes Bénédicte , Sequeira-Mendes Joana , Masoud Kinda , Costas Celina , Noir Sandra , Caro Elena , Mora-Gil Victoria , Genschik Pascal , Gutierrez Crisanto
Published: March 2023

Most cellular proteins involved in genome replication are conserved in all eukaryotic lineages including yeast, plants and animals. However, the mechanisms controlling their availability during the cell cycle are less well defined. Here we show that the Arabidopsis genome encodes for two ORC1 proteins highly similar in amino acid sequence and that have partially overlapping expression domains but with distinct functions. The ancestralORC1bgene, present before the partial duplication of the Arabidopsis genome, has retained the canonical function in DNA replication. ORC1b is expressed in both proliferating and endoreplicating cells, accumulates during G1 and is rapidly degraded upon S-phase entry through the ubiquitin-proteasome pathway. In contrast, the duplicatedORC1agene has acquired a specialized function in heterochromatin biology. ORC1a is required for efficient deposition of the heterochromatic H3K27me1 mark by the ATXR5/6 histone methyltransferases. The distinct roles of the two ORC1 proteins may be a feature common to other organisms with duplicatedORC1genes and a major difference with animal cells.
Fully 3D-printed organic electrochemical transistors
Authors: Massetti Matteo , Zhang Silan , Harikesh Padinhare Cholakkal , Burtscher Bernhard , Diacci Chiara , Simon Daniel T. , Liu Xianjie , Fahlman Mats , Tu Deyu , Berggren Magnus , Fabiano Simone
Published: March 2023

Organic electrochemical transistors (OECTs) are being researched for various applications, ranging from sensors to logic gates and neuromorphic hardware. To meet the requirements of these diverse applications, the device fabrication process must be compatible with flexible and scalable digital techniques. Here, we report a direct-write additive process to fabricate fully 3D-printed OECTs, using 3D printable conducting, semiconducting, insulating, and electrolyte inks. These 3D-printed OECTs, which operate in the depletion mode, can be fabricated on flexible substrates, resulting in high mechanical and environmental stability. The 3D-printed OECTs have good dopamine biosensing capabilities (limit of detection down to 6 µM without metal gate electrodes) and show long-term (~1 h) synapse response, indicating their potential for various applications such as sensors and neuromorphic hardware. This manufacturing strategy is suitable for applications that require rapid design changes and digitally enabled direct-write techniques.
Deficiency of Perry syndrome-associated p150Glued in midbrain dopaminergic neurons leads to progressive neurodegeneration and endoplasmic reticulum abnormalities
Authors: Yu Jia , Yang Xuan , Zheng Jiayin , Sgobio Carmelo , Sun Lixin , Cai Huaibin
Published: March 2023

Multiple missense mutations in p150Glued are linked to Perry syndrome (PS), a rare neurodegenerative disease pathologically characterized by loss of nigral dopaminergic (DAergic) neurons. Here we generated p150Glued conditional knockout (cKO) mice by deleting p150Glued in midbrain DAergic neurons. The young cKO mice displayed impaired motor coordination, dystrophic DAergic dendrites, swollen axon terminals, reduced striatal dopamine transporter (DAT), and dysregulated dopamine transmission. The aged cKO mice showed loss of DAergic neurons and axons, somatic accumulation of α-synuclein, and astrogliosis. Further mechanistic studies revealed that p150Glued deficiency in DAergic neurons led to the reorganization of endoplasmic reticulum (ER) in dystrophic dendrites, upregulation of ER tubule-shaping protein reticulon 3, accumulation of DAT in reorganized ERs, dysfunction of COPII-mediated ER export, activation of unfolded protein response, and exacerbation of ER stress-induced cell death. Our findings demonstrate the importance of p150Glued in controlling the structure and function of ER, which is critical for the survival and function of midbrain DAergic neurons in PS.
MFCSC: Novel method to calculate mismatch between functional and structural brain connectomes, and its application for detecting hemispheric functional specialisations
Authors: Civier Oren , Sourty Marion , Calamante Fernando
Published: March 2023

We introduce a novel connectomics method, MFCSC, that integrates information on structural connectivity (SC) from diffusion MRI tractography and functional connectivity (FC) from functional MRI, at individual subject level. The MFCSC method is based on the fact that SC only broadly predicts FC, and for each connection in the brain, the method calculates a value that quantifies the mismatch that often still exists between the two modalities. To capture underlying physiological properties, MFCSC minimises biases in SC and addresses challenges with the multimodal analysis, including by using a data-driven normalisation approach. We ran MFCSC on data from the Human Connectome Project and used the output to detect pairs of left and right unilateral connections that have distinct relationship between structure and function in each hemisphere; we suggest that this reflects cases of hemispheric functional specialisation. In conclusion, the MFCSC method provides new information on brain organisation that may not be inferred from an analysis that considers SC and FC separately.
In vivo multi-parameter mapping of the habenula using MRI
Authors: Milotta Giorgia , Green Isobel , Roiser Jonathan P. , Callaghan Martina F.
Published: March 2023

The habenula is a small, epithalamic brain structure situated between the mediodorsal thalamus and the third ventricle. It plays an important role in the reward circuitry of the brain and is implicated in psychiatric conditions, such as depression. The importance of the habenula for human cognition and mental health make it a key structure of interest for neuroimaging studies. However, few studies have characterised the physical properties of the human habenula using magnetic resonance imaging because its challenging visualisation in vivo, primarily due to its subcortical location and small size. To date, microstructural characterization of the habenula has focused on quantitative susceptibility mapping. In this work, we complement this previous characterisation with measures of longitudinal and effective transverse relaxation rates, proton density and magnetisation transfer saturation using a high-resolution quantitative multi-parametric mapping protocol at 3T, in a cohort of 26 healthy participants. The habenula had consistent boundaries across the various parameter maps and was most clearly visualised on the longitudinal relaxation rate maps. We have provided a quantitative multi-parametric characterisation that may be useful for future sequence optimisation to enhance visualisation of the habenula, and additionally provides reference values for future studies investigating pathological differences in habenula microstructure.
On electromagnetic head digitization in MEG and EEG
Authors: Jaiswal Amit , Nenonen Jukka , Parkkonen Lauri
Published: March 2023

In MEG and EEG studies, the accuracy of the head digitization impacts the co-registration between functional and structural data. The co-registration is one of the major factors that affect the spatial accuracy in MEG/EEG source imaging. Precisely digitized head-surface (scalp) points do not only improve the co-registration but can also deform a template MRI. Such an individualized-template MRI can be used for conductivity modeling in MEG/EEG source imaging if the individual’s structural MRI is unavailable. Electromagnetic tracking (EMT) systems (particularly Fastrak, Polhemus Inc., Colchester, VT, USA) have been the most common solution for digitization in MEG and EEG. However, they may occasionally suffer from ambient electromagnetic interference which makes it challenging to achieve (sub-)millimeter digitization accuracy. The current study—(i) evaluated the performance of the Fastrak EMT system under different conditions in MEG/EEG digitization, and (ii) explores the usability of two alternative EMT systems (Aurora, NDI, Waterloo, ON, Canada; Fastrak with a short-range transmitter) for digitization. Tracking fluctuation, digitization accuracy, and robustness of the systems were evaluated in several test cases using test frames and human head models. The performance of the two alternative systems was compared against the Fastrak system. The results showed that the Fastrak system is accurate and robust for MEG/EEG digitization if the recommended operating conditions are met. The Fastrak with the short-range transmitter shows comparatively higher digitization error if digitization is not carried out very close to the transmitter. The study also evinces that the Aurora system can be used for MEG/EEG digitization within a constrained range; however, some modifications would be required to make the system a practical and easy-to-use digitizer. Its real-time error estimation feature can potentially improve digitization accuracy.
Histone H3-wild type diffuse midline gliomas with H3K27me3 loss are a distinct entity with exclusive EGFR or ACVR1 mutation and differential methylation of homeobox genes
Authors: Ajuyah Pamela , Mayoh Chelsea , Lau Loretta M. S. , Barahona Paulette , Wong Marie , Chambers Hazel , Valdes-Mora Fatima , Senapati Akanksha , Gifford Andrew J. , D’Arcy Colleen , Hansford Jordan R. , Manoharan Neevika , Nicholls Wayne , Williams Molly M. , Wood Paul J. , Cowley Mark J. , Tyrrell Vanessa , Haber Michelle , Ekert Paul G. , Ziegler David S. , Khuong-Quang Dong-Anh
Published: March 2023

Diffuse midline gliomas (DMG) harbouring H3K27M mutation are paediatric tumours with a dismal outcome. Recently, a new subtype of midline gliomas has been described with similar features to DMG, including loss of H3K27 trimethylation, but lacking the canonical H3K27M mutation (H3-WT). Here, we report a cohort of five H3-WT tumours profiled by whole-genome sequencing, RNA sequencing and DNA methylation profiling and combine their analysis with previously published cases. We show that these tumours have recurrent and mutually exclusive mutations in either ACVR1 or EGFR and are characterised by high expression of EZHIP associated to its promoter hypomethylation. Affected patients share a similar poor prognosis as patients with H3K27M DMG. Global molecular analysis of H3-WT and H3K27M DMG reveal distinct transcriptome and methylome profiles including differential methylation of homeobox genes involved in development and cellular differentiation. Patients have distinct clinical features, with a trend demonstrating ACVR1 mutations occurring in H3-WT tumours at an older age. This in-depth exploration of H3-WT tumours further characterises this novel DMG, H3K27-altered sub-group, characterised by a specific immunohistochemistry profile with H3K27me3 loss, wild-type H3K27M and positive EZHIP. It also gives new insights into the possible mechanism and pathway regulation in these tumours, potentially opening new therapeutic avenues for these tumours which have no known effective treatment.

This study has been retrospectively registered on clinicaltrial.gov on 8 November 2017 under the registration number NCT03336931 (https://clinicaltrials.gov/ct2/show/NCT03336931).
The efficiency of quantum teleportation with three-qubit entangled state in a noisy environment
Authors: Zhang Chang-Yue , Zheng Zhu-Jun , Fan Zhao-Bing , Ma Hai-Tao
Published: March 2023

Quantum teleportation plays a significant role in the field of quantum communication. This paper investigates quantum teleportation through a noisy environment by using GHZ state and non-standard W state as quantum channels. We analyze the efficiency of quantum teleportation by solving analytically a master equation in Lindblad form. Following the quantum teleportation protocol, we obtain the fidelity of quantum teleportation as a function of evolution time. The calculation results show that the teleportation fidelity using non-standard W is higher in comparison to GHZ state at the same evolution time. Moreover, we consider the efficiency of teleportation with weak measurements and reverse quantum measurement under amplitude damping noise. Our analysis suggests that the teleportation fidelity using non-standard W is also more robust to noise than GHZ state in the same conditions. Interestingly, we found that weak measurement and its reverse operation have no positive effect on the efficiency of quantum teleportation by using GHZ and non-standard W state in the amplitude damping noise environment. In addition, we also demonstrate the efficiency of quantum teleportation can be improved by making minor modifications to the protocol.