bluuebunny/crossref_metadata_2025 huggingface dataset:
A homogenised model for the motion of evaporating fronts in porous media
Authors: Luckins Ellen K. , Breward Christopher J. W. , Griffiths Ian M. , Please Colin P.
Published: January 2023

Evaporation within porous media is both a multiscale and interface-driven process, since the phase change at the evaporating interfaces within the pores generates a vapour flow and depends on the transport of vapour through the porous medium. While homogenised models of flow and chemical transport in porous media allow multiscale processes to be modelled efficiently, it is not clear how the multiscale effects impact the interface conditions required for these homogenised models. In this paper, we derive a homogenised model, including effective interface conditions, for the motion of an evaporation front through a porous medium, using a combined homogenisation and boundary layer analysis. This analysis extends previous work for a purely diffusive problem to include both gas flow and the advective–diffusive transport of material. We investigate the effect that different microscale models describing the chemistry of the evaporation have on the homogenised interface conditions. In particular, we identify a new effective parameter,$\mathcal{L}$, the average microscale interface length, which modifies the effective evaporation rate in the homogenised model. Like the effective diffusivity and permeability of a porous medium,$\mathcal{L}$may be found by solving a periodic cell problem on the microscale. We also show that the different microscale models of the interface chemistry result in fundamentally different fine-scale behaviour at, and near, the interface.
The (Re-)construction of Monuments in Germany: New Historical Narratives in a Time of Nation-building
Authors: Kott Sandrine , Wieder Thomas
Published: January 2023

In the slipstream of the Black Lives Matter movement in the United States, there has been a global mobilisation around monuments and statues of famous figures involved in the slave trade and European colonial conquest. In former colonial states – such as France and Britain – and states shaped by the legacies of slavery – such as the United States – activists have defaced, damaged or torn down monuments associated with these contested pasts. This is hardly a novelty. The destruction of physical symbols is often a response to regime change. But, in this case, the mobilisation has taken a different form. Instead of legitimising a new regime and new elites, the destruction of monuments is part of a demand for justice from historically marginalised groups who are seeking to reclaim their heritage. The deconstruction of these monuments automatically entails the deconstruction of dominant national narratives that have contributed to such marginalisation.
Contemporary History as an Intrusion into Personal Memory: Methodological Dilemmas, Public Presence and the Perils of Presentism
Authors: Hatzivassiliou Evanthis
Published: January 2023

In a brilliant 1972 cartoon, the creator of Snoopy, Charles M. Schulz, depicts the contemplative beagle going through a crisis of rage. Snoopy discovers that a six-storey parking garage has been built on the site of the Daisy Hill Puppy Farm, a place in which, we are led to understand, he had spent some of his happiest childhood moments. Snoopy cannot contain himself. ‘You stupid people’, he shouts; ‘You're parking on my memories’.
When History Matters Too Much: Historians and the Politics of History in Poland
Authors: Machcewicz Paweł
Published: January 2023

Academic historians often complain that their work is not appreciated by the public and that the impact of their books is limited to a few other scholars. There are, however, situations where historians face the opposite challenge, namely a great deal of interest from both the public and from politicians who want to exploit or interfere with their work to further their political agendas. This arises most often in countries that are undergoing deep political and social changes. At these times, the legacies of the past that emerge after a fundamental regime transformation, like the collapse of dictatorship, have a profound impact on historical research and discourse.
Scholars and the Politics of International Art Restitution
Authors: Subotic Jelena
Published: January 2023

Almost every week brings news of another major European museum agreeing to return looted art. Since the 2000s we have grown somewhat accustomed to the headlines describing a ceremonial return to its original owners of a painting looted in the Holocaust, a process that took decades to develop and was initially met with considerable resistance in the art world and in the countries where this art was displayed.1 In the past few years, however, building in part on the perceived success of Holocaust art restitution but also on the increased visibility and impact of national and global social movements demanding racial justice and institutional decolonisation, major international museums have come under ever stronger pressure to return art looted as part of colonial occupations. Perhaps the most organised of the current campaigns is the campaign to return the so-called ‘Benin Bronzes’ – a vast collection of various artifacts looted from the Kingdom of Benin (in today's Nigeria) and dispersed across major international museums, most prominently the British Museum in London, the Ethnological Museum in Berlin, and the Musée du quai Branly in Paris, among others. Since 2020, a number of museums have pledged to return their holdings of Benin Bronzes and restitute them to Nigeria, where a major new museum is being built to display them in Benin City. All of this activity has also reenergised perhaps the most famous case for restitution – the movement to return the Parthenon ‘Elgin’ marbles from the British Museum to the Acropolis in Athens.
Putin's Histories
Authors: Radchenko Sergey
Published: January 2023

One day in December 2019 I knew something was badly amiss. Russian President Vladimir Putin had called a meeting with the leaders of the Commonwealth of Independent States – the vague post-Soviet association of former Soviet republics that semi-defer to Russia – in order to discuss history. Not just discuss: he actually brought a thick stack of archival documents to the meeting, which, he said, demonstrated certain truths about the history of the Second World War. These had allegedly been forgotten or perhaps deliberately ignored in the West. He then selectively cited from these documents (most, if not all, of which are well-known to historians) to prove that, effectively, the West, and especially Poland, were responsible for the war.
Confronting the Past: The Role of the European Historian Today
Authors: Chabal Emile , Karamouzi Eirini
Published: January 2023

The pandemic may have consigned historians to their homes, but this did not stop history from taking centre-stage in public debate. From falling statues to culture wars, history in all its forms has continued to be deployed by states, activists, prestigious institutions and grassroots organisations. As has always been the case, those who study history for a living have rarely played a prominent role in these debates. At best, historians have tended to be confined to supporting roles as ‘advisers’, ‘consultants’ or ‘experts’. Still, even for those historians who eschew the rough-and-tumble of political and civic discussion, it is impossible to remain entirely neutral. Governments and politicians can overturn funding priorities; universities can suddenly find themselves targets of hostile political campaigning; and lecture halls can turn into sites of civic struggle. This constant historical instrumentalisation is a dramatic reminder of the power of narratives in constructing realities.
Administrative Literacy in the Digital Welfare State: Migrants Navigating Access to Public Services in Finland
Authors: Safarov Nuriiar
Published: January 2023

The digitalisation of public services brought challenges for their access and use. This article looks at the migrants as claimants of the public services to analyse the problems with the digital delivery of public services. The previous research recognised the various resources, such as digital skills and administrative literacy, needed for the successful use of digital services. However, the role of administrative literacy has not been studied in linguistically and culturally diverse contexts, such as migration. This article draws on the qualitative study of Russian-speaking migrants in Finland. By analysing the perspective of the service users, it describes in detail the requirements that people with migrant backgrounds try to meet to gain access to social protection. Findings demonstrate the multiple obstacles that burden or prevent access to entitlements.
Donizetti's Self-Borrowings as an Artistic Practice
Authors: Mantica Candida Billie
Published: January 2023

Gaetano Donizetti's versatile production unfolded over three decades (1818–43) and was staged in the foremost Italian and European theatres. In this article I question his self-borrowing as a chiefly economic practice, offering novel keys to reading his re-use of existing materials. In the introductory section, I offer a preliminary discussion of the coeval discourse on Donizetti's self-imitation as it surfaces in the press, which appears to follow in the footsteps of that on Rossini's. I then look at his self-borrowings across genres, dwelling on the ways in which he re-functionalized earlier serious passages within comic frames, almost inevitably to achieve a parodic effect. After discussing the links between parody and diegetic music – one of his favourite contexts for employing older materials – I turn to Donizetti's serious production, advancing the hypothesis that his recourse to self-borrowing could take on semantic connotations. In so doing, in the second part of the article I focus on selected case studies grouped into three thematic areas, which – similarly to, and occasionally in connection with diegetic music – all involve the suspension of a character's habitual idioms: deception, rituals and madness. The article includes extended examples from the composer'sLinda di Chamounix(Vienna, Kärntnertortheater, 1842),Sancia di Castiglia(Naples, Teatro San Carlo, 1832),Il paria(Naples, Teatro San Carlo, 1829),Marino Faliero(Paris, Théâtre-Italien, 1835),Enrico di Borgogna(Venice, Teatro San Luca, 1818), andAnna Bolena(Milan, Teatro Carcano, 1830). My ultimate concern is to demonstrate that Donizetti's use of self-borrowing could perform a dramatic function, deliberately connoting the altered modes of expression of the characters to which the earlier piece is associated.
Strain Localization: Analog Modeling and Anisotropy of Magnetic Susceptibility
Authors: Roxerová Zuzana , Machek Matěj , Kusbach Vladimír K. , Vávrová Anna
Published: January 2023

The majority of the strain in Earth crust and upper mantle is localized to the high strain zones developed at ductile‐to‐brittle condition at kilometer‐to‐micrometer scale. Therefore, they represent the key to understanding the deformation evolution of the lithosphere. The finite strain pattern recorded within these zones has been therefore a subject of research in geology. The methods studying rock magnetism such as the anisotropy of magnetic susceptibility (AMS) are frequently used techniques to characterize and quantify deformation and flow record in rocks. Numerous sedimentary, subsolidus and submagmatic deformation zones exhibit typical evolution of the AMS ellipsoid across the strain gradient suggesting indirect not straightforward correlation between AMS and strain ellipsoids. To document spatiotemporal and internal fabric evolution during strain localization, pure shear, simple shear, and shear zone (SZ) analog experiments were performed using shear‐thinning thixotropic material of plaster of Paris. The experimental results closely resemble the record from natural SZs in sedimentary rock systems but also in subsolidus SZs and submagmatic mushy systems. The magnetic fabric evolution across deformation zones is interpreted to be associated with the intersection and transposition of preexisting primary fabric with shear fabrics and evolution of synkinematic subfabrics. Their development is attributed to localization of deformation at microscale due to the self‐organized slip of anisometric particles forming microshear planes reflecting the symmetry of deformation. The experimental results when confronted with the natural examples implies that the localization and partitioning of deformation is one of the most important factors for the interpretation of AMS in deformation zones.
Bayesian Inversion of Finite‐Fault Earthquake Slip Model Using Geodetic Data, Solving for Non‐Planar Fault Geometry, Variable Slip, and Data Weighting
Authors: Wei Guoguang , Chen Kejie , Meng Haoran
Published: January 2023

A precise finite‐fault model including the fault geometry and slip distribution is essential to understand the physics of an earthquake. However, the conventional linear inversion of geodetic data for a finite‐fault model cannot fully resolve the fault geometry. In this study, we developed a Bayesian inversion framework that can comprehensively solve a non‐planar fault geometry, the corresponding fault slip distribution with spatially variable directions, and objective weighting for multiple data types. In the proposed framework, the probability distributions of all the model parameters are sampled using the Monte Carlo method. The developed methodology removes the requirement for manual intervention for the fault geometry and data weighting and can provide an ensemble of plausible model parameters. The performance of the developed method is tested and demonstrated through inversions for synthetic oblique‐slip faulting models. The results show that the constant rake assumption can significantly bias the estimates of fault geometry and data weighting, whereas additional consideration of the variability of slip orientations can allow plausible estimates of a non‐planar fault geometry with objective data weighting. We applied the method to the 2013 Mw 6.5 Lushan earthquake in Sichuan province, China. The result reveals dominant thrust slips with left‐lateral components and a curved fault geometry, with the confidence interval of the dip angles being between 20°–25° and 56°–58°. The proposed method provides useful insights into the scope of imaging a non‐planar fault geometry, and could help to interpret more complex earthquake sources in the future.
Toward an Integrated Probabilistic Coastal Vulnerability Assessment: A Novel Copula‐Based Vulnerability Index
Authors: Tanim Ahad Hasan , Goharian Erfan
Published: January 2023

Estimating the exposure of the coastal systems to natural hazards using coastal vulnerability models, which benefits from index‐based approaches and utilize information about the characteristics of the system, has become extensively adopted in the past few decades in coastal management and planning. However, the explanatory power of index‐based approaches and subjective selection of vulnerability factors are still in dispute. This study aims to introduce a stochastic coastal vulnerability model and assess its skill in characterizing and preserving simultaneous information about various comprising factors. Two common coastal vulnerability indices, Additive Coastal Vulnerability Index and Multiplicative Coastal Vulnerability Index are formed, and then their performances are compared to the proposed Probabilistic Coastal Vulnerability Index (PCVI) for the coastal counties of South Carolina. PCVI is developed based on the joint‐probability analysis of vulnerability factors using copula functions, which makes it capable of preserving the importance of multivariate information, and in turn, forms a more informative index. The performance of indices is benchmarked against post‐hazard flood maps and the cost of fatalities from Hurricane Florence (2018) and Hurricane Matthew (2016). The PCVI revealed more accurate results in terms of explaining the importance of vulnerability associated with biophysical and socio‐economic factors. The capability of PCVI to preserve multivariate vulnerability information offers a more pragmatic approach to reflect the exposure and adaptive capacity of coastal communities facing coastal hazards.
Novel D-glutamate catabolic pathway in marine Proteobacteria and halophilic archaea
Authors: Yu Yang , Wang Peng , Cao Hai-Yan , Teng Zhao-Jie , Zhu Yanping , Wang Min , McMinn Andrew , Chen Yin , Xiang Hua , Zhang Yu-Zhong , Chen Xiu-Lan , Zhang Yu-Qiang
Published: January 2023

D-glutamate (D-Glu) is an essential component of bacterial peptidoglycans, representing an important, yet overlooked, pool of organic matter in global oceans. However, little is known on D-Glu catabolism by marine microorganisms. Here, a novel catabolic pathway for D-Glu was identified using the marine bacterium Pseudoalteromonas sp. CF6-2 as the model. Two novel enzymes (DgcN, DgcA), together with a transcriptional regulator DgcR, are crucial for D-Glu catabolism in strain CF6-2. Genetic and biochemical data confirm that DgcN is a N-acetyltransferase which catalyzes the formation of N-acetyl-D-Glu from D-Glu. DgcA is a racemase that converts N-acetyl-D-Glu to N-acetyl-L-Glu, which is further hydrolyzed to L-Glu. DgcR positively regulates the transcription of dgcN and dgcA. Structural and biochemical analyses suggested that DgcN and its homologs, which use D-Glu as the acyl receptor, represent a new group of the general control non-repressible 5 (GCN5)-related N-acetyltransferases (GNAT) superfamily. DgcA and DgcN occur widely in marine bacteria (particularly Rhodobacterales) and halophilic archaea (Halobacteria) and are abundant in marine and hypersaline metagenome datasets. Thus, this study reveals a novel D-Glu catabolic pathway in ecologically important marine bacteria and halophilic archaea and helps better understand the catabolism and recycling of D-Glu in these ecosystems.
Approximating defense mechanisms in a national study of adults: prevalence and correlates with functioning
Authors: Blanco Carlos , Kampe Leonie , Wall Melanie M. , Liu Shang-Min , Wang Shuai , Caligor Eve , Olfson Mark
Published: January 2023

Despite the clinical relevance of defense mechanisms, there are no published studies in nationally representative samples of their prevalence, correlates, and association with psychosocial functioning. We sought to estimate the prevalence and correlates of 12 defense mechanisms in the general adult population by approximating from items used to assess personality traits in the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a representative sample of US adults (N = 36,653). We examined the associations between sociodemographic characteristics and prevalence of 3 types of defenses mechanisms (pathological, immature, and neurotic). For each defense mechanism, we used the Short-Form 12 to compare psychosocial functioning among 3 groups: those who (1) endorsed the mechanism with self-recognized impairment, (2) endorsed the mechanism without self-recognized impairment, and (3) did not endorse the defense mechanism. The prevalence of defense mechanisms ranged from 13.2% (splitting) to 44.5% (obsessive/controlling behavior). Pathological defenses were more strongly associated with immature defenses (OR = 5.4, 95% CI = 5.2–5.6) than with neurotic defenses (OR = 2.0, 95% CI = 1.9–2.0), whereas the association between immature and neurotic defenses had an intermediate value between the other two (OR = 2.2, 95% CI = 2.1–2.2). Pathological and immature defenses were associated with younger age, having been never married, lower educational attainment, and lower income. After adjusting the crude results for age and sex, individuals who did not endorse a given defense generally had higher scores on the mental health component of the SF-12 than those who endorsed the defense without self-recognized impairment who, in turn, had on average higher scores than those with self-recognized impairment. These results suggest that neurotic, immature, and pathological defense mechanisms are prevalent in the general population and associated with psychosocial impairment. Recognizing defense mechanisms may be important in clinical practice regardless of treatment modality.
Prognostic refinement of NSMP high-risk endometrial cancers using oestrogen receptor immunohistochemistry
Authors: Vermij Lisa , Jobsen Jan J. , León-Castillo Alicia , Brinkhuis Mariel , Roothaan Suzan , Powell Melanie E. , de Boer Stephanie M. , Khaw Pearly , Mileshkin Linda R. , Fyles Anthony , Leary Alexandra , Genestie Catherine , Jürgenliemk-Schulz Ina M. , Crosbie Emma J. , Mackay Helen J. , Nijman Hans. W. , Nout Remi A. , Smit Vincent T. H. B. M. , Creutzberg Carien L. , Horeweg Nanda , Bosse Tjalling ,   TransPORTEC Consortium, de Boer Stephanie M.
Published: January 2023

Background

Risk-assessment of endometrial cancer (EC) is based on clinicopathological factors and molecular subgroup. It is unclear whether adding hormone receptor expression, L1CAM expression or CTNNB1 status yields prognostic refinement.

Methods

Paraffin-embedded tumour samples of women with high-risk EC (HR-EC) from the PORTEC-3 trial (n = 424), and a Dutch prospective clinical cohort called MST (n = 256), were used. All cases were molecularly classified. Expression of L1CAM, ER and PR were analysed by whole-slide immunohistochemistry and CTNNB1 mutations were assessed with a next-generation sequencing. Kaplan–Meier method, log-rank tests and Cox’s proportional hazard models were used for survival analysis.

Results

In total, 648 HR-EC were included. No independent prognostic value of ER, PR, L1CAM, and CTNNB1 was found, while age, stage, and adjuvant chemotherapy had an independent impact on risk of recurrence. Subgroup-analysis showed that only in NSMP HR-EC, ER-positivity was independently associated with a reduced risk of recurrence (HR 0.33, 95%CI 0.15–0.75).

Conclusions

We confirmed the prognostic impact of the molecular classification, age, stage, and adjuvant CTRT in a large cohort of high-risk EC. ER-positivity is a strong favourable prognostic factor in NSMP HR-EC and identifies a homogeneous subgroup of NSMP tumours. Assessment of ER status in high-risk NSMP EC is feasible in clinical practice and could improve risk stratification and treatment.
The mitochondrial inhibitor IF1 binds to the ATP synthase OSCP subunit and protects cancer cells from apoptosis
Authors: Galber Chiara , Fabbian Simone , Gatto Cristina , Grandi Martina , Carissimi Stefania , Acosta Manuel Jesus , Sgarbi Gianluca , Tiso Natascia , Argenton Francesco , Solaini Giancarlo , Baracca Alessandra , Bellanda Massimo , Giorgio Valentina
Published: January 2023

The mitochondrial protein IF1 binds to the catalytic domain of the ATP synthase and inhibits ATP hydrolysis in ischemic tissues. Moreover, IF1 is overexpressed in many tumors and has been shown to act as a pro-oncogenic protein, although its mechanism of action is still debated. Here, we show that ATP5IF1 gene disruption in HeLa cells decreases colony formation in soft agar and tumor mass development in xenografts, underlining the role of IF1 in cancer. Notably, the lack of IF1 does not affect proliferation or oligomycin-sensitive mitochondrial respiration, but it sensitizes the cells to the opening of the permeability transition pore (PTP). Immunoprecipitation and proximity ligation analysis show that IF1 binds to the ATP synthase OSCP subunit in HeLa cells under oxidative phosphorylation conditions. The IF1–OSCP interaction is confirmed by NMR spectroscopy analysis of the recombinant soluble proteins. Overall, our results suggest that the IF1-OSCP interaction protects cancer cells from PTP-dependent apoptosis under normoxic conditions.
Development of a versatile nuclease prime editor with upgraded precision
Authors: Li Xiangyang , Zhang Guiquan , Huang Shisheng , Liu Yao , Tang Jin , Zhong Mingtian , Wang Xin , Sun Wenjun , Yao Yuan , Ji Quanjiang , Wang Xiaolong , Liu Jianghuai , Zhu Shiqiang , Huang Xingxu
Published: January 2023

The applicability of nuclease-based form of prime editor (PEn) has been hindered by its complexed editing outcomes. A chemical inhibitor against DNA-PK, which mediates the nonhomologous end joining (NHEJ) pathway, was recently shown to promote precise insertions by PEn. Nevertheless, the intrinsic issues of specificity and toxicity for such a chemical approach necessitate development of alternative strategies. Here, we find that co-introduction of PEn and a NHEJ-restraining, 53BP1-inhibitory ubiquitin variant potently drives precise edits via mitigation of unintended edits, framing a high-activity editing platform (uPEn) apparently complementing the canonical PE. Further developments involve exploring the effective configuration of a homologous region-containing pegRNA (HR-pegRNA). Overall, uPEn can empower high-efficiency installation of insertions (38%), deletions (43%) and replacements (52%) in HEK293T cells. When compared with PE3/5max, uPEn demonstrates superior activities for typically refractory base substitutions, and for small-block edits. Collectively, this work establishes a highly efficient PE platform with broad application potential.
Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry
Authors: Rizzato Matteo , Mao Fuxiang , Chardon Florian , Lai Kun-Yi , Villalonga-Planells Ruth , Drexler Hannes C. A. , Pesenti Marion E. , Fiskin Mert , Roos Nora , King Kelly M. , Li Shuaizhi , Gamez Eduardo R. , Greune Lilo , Dersch Petra , Simon Claudia , Masson Murielle , Van Doorslaer Koenraad , Campos Samuel K. , Schelhaas Mario
Published: January 2023

Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis.
Strong room-temperature bulk nonlinear Hall effect in a spin-valley locked Dirac material
Authors: Min Lujin , Tan Hengxin , Xie Zhijian , Miao Leixin , Zhang Ruoxi , Lee Seng Huat , Gopalan Venkatraman , Liu Chao-Xing , Alem Nasim , Yan Binghai , Mao Zhiqiang
Published: January 2023

Nonlinear Hall effect (NLHE) is a new type of Hall effect with wide application prospects. Practical device applications require strong NLHE at room temperature (RT). However, previously reported NLHEs are all low-temperature phenomena except for the surface NLHE of TaIrTe4. Bulk RT NLHE is highly desired due to its ability to generate large photocurrent. Here, we show the spin-valley locked Dirac state in BaMnSb2 can generate a strong bulk NLHE at RT. In the microscale devices, we observe the typical signature of an intrinsic NLHE, i.e. the transverse Hall voltage quadratically scales with the longitudinal current as the current is applied to the Berry curvature dipole direction. Furthermore, we also demonstrate our nonlinear Hall device’s functionality in wireless microwave detection and frequency doubling. These findings broaden the coupled spin and valley physics from 2D systems into a 3D system and lay a foundation for exploring bulk NLHE’s applications.
Mechanisms and function of de novo DNA methylation in placental development reveals an essential role for DNMT3B
Authors: Andrews Simon , Krueger Christel , Mellado-Lopez Maravillas , Hemberger Myriam , Dean Wendy , Perez-Garcia Vicente , Hanna Courtney W.
Published: January 2023

DNA methylation is a repressive epigenetic modification that is essential for development, exemplified by the embryonic and perinatal lethality observed in mice lacking de novo DNA methyltransferases (DNMTs). Here we characterise the role for DNMT3A, 3B and 3L in gene regulation and development of the mouse placenta. We find that each DNMT establishes unique aspects of the placental methylome through targeting to distinct chromatin features. Loss of Dnmt3b results in de-repression of germline genes in trophoblast lineages and impaired formation of the maternal-foetal interface in the placental labyrinth. Using Sox2-Cre to delete Dnmt3b in the embryo, leaving expression intact in placental cells, the placental phenotype was rescued and, consequently, the embryonic lethality, as Dnmt3b null embryos could now survive to birth. We conclude that de novo DNA methylation by DNMT3B during embryogenesis is principally required to regulate placental development and function, which in turn is critical for embryo survival.
RSL24D1 sustains steady-state ribosome biogenesis and pluripotency translational programs in embryonic stem cells
Authors: Durand Sébastien , Bruelle Marion , Bourdelais Fleur , Bennychen Bigitha , Blin-Gonthier Juliana , Isaac Caroline , Huyghe Aurélia , Martel Sylvie , Seyve Antoine , Vanbelle Christophe , Adrait Annie , Couté Yohann , Meyronet David , Catez Frédéric , Diaz Jean-Jacques , Lavial Fabrice , Ricci Emiliano P. , Ducray François , Gabut Mathieu
Published: January 2023

Embryonic stem cell (ESC) fate decisions are regulated by a complex circuitry that coordinates gene expression at multiple levels from chromatin to mRNA processing. Recently, ribosome biogenesis and translation have emerged as key pathways that efficiently control stem cell homeostasis, yet the underlying molecular mechanisms remain largely unknown. Here, we identified RSL24D1 as highly expressed in both mouse and human pluripotent stem cells. RSL24D1 is associated with nuclear pre-ribosomes and is required for the biogenesis of 60S subunits in mouse ESCs. Interestingly, RSL24D1 depletion significantly impairs global translation, particularly of key pluripotency factors and of components from the Polycomb Repressive Complex 2 (PRC2). While having a moderate impact on differentiation, RSL24D1 depletion significantly alters ESC self-renewal and lineage commitment choices. Altogether, these results demonstrate that RSL24D1-dependant ribosome biogenesis is both required to sustain the expression of pluripotent transcriptional programs and to silence PRC2-regulated developmental programs, which concertedly dictate ESC homeostasis.
Video-rate hyperspectral camera based on a CMOS-compatible random array of Fabry–Pérot filters
Authors: Yako Motoki , Yamaoka Yoshikazu , Kiyohara Takayuki , Hosokawa Chikai , Noda Akihiro , Tack Klaas , Spooren Nick , Hirasawa Taku , Ishikawa Atsushi
Published: January 2023

Hyperspectral (HS) imaging provides rich spatial and spectral information and extends image inspection beyond human perception. Existing approaches, however, suffer from several drawbacks such as low sensitivity, resolution and/or frame rate, which confines HS cameras to scientific laboratories. Here we develop a video-rate HS camera capable of collecting spectral information on real-world scenes with sensitivities and spatial resolutions comparable with those of a typical RGB camera. Our camera uses compressive sensing, whereby spatial–spectral encoding is achieved with an array of 64 complementary metal–oxide–semiconductor (CMOS)-compatible Fabry–Pérot filters placed onto a monochromatic image sensor. The array affords high optical transmission while minimizing the reconstruction error in subsequent iterative image reconstruction. The experimentally measured sensitivity of 45% for visible light, the spatial resolution of 3 px for 3 dB contrast, and the frame rate of 32.3 fps at VGA resolution meet the requirements for practical use. For further acceleration, we show that AI-based image reconstruction affords operation at 34.4 fps and full high-definition resolution. By enabling practical sensitivity, resolution and frame rate together with compact size and data compression, our HS camera holds great promise for the adoption of HS technology in real-world scenarios, including consumer applications such as smartphones and drones.
Comprehensive liquid biopsy analysis as a tool for the early detection of minimal residual disease in breast cancer
Authors: Stergiopoulou Dimitra , Markou Athina , Strati Areti , Zavridou Martha , Tzanikou Eleni , Mastoraki Sophia , Kallergi Galatea , Georgoulias Vassilis , Lianidou Evi
Published: January 2023

Liquid biopsy (LB) provides a unique minimally invasive tool to follow-up cancer patients over time, to detect minimal residual disease (MRD), to study metastasis-biology and mechanisms of therapy-resistance. Molecular characterization of CTCs offers additionally the potential to understand resistance to therapy and implement individualized targeted treatments which can be modified during the disease evolution and follow-up period of a patient. In this study, we present a long-term follow-up of operable breast cancer patients based on a comprehensive liquid biopsy analysis. We performed a comprehensive liquid biopsy analysis in peripheral blood of 13 patients with early-stage operable breast cancer at several time points for a period of ten years, consisting of: (a) CTC enumeration using the CellSearch system, (b) phenotypic analysis of CTCs using Immunofluorescence, (c) gene expression analysis, in EpCAM(+) CTCs for CK-19, CD24,CD44, ALDH1, and TWIST1, (d) analysis of PIK3CA and ESR1 mutations in EpCAM(+) CTCs and corresponding plasma ctDNA and (e) DNA methylation of ESR1 in CTCs. 10/13 (77%) patients were found negative for LB markers in PB during the whole follow-up period, and these patients did not relapse during the follow-up. However, 3/13(18%) patients that were positive for at least one LB marker relapsed within the follow-up period. The molecular characteristics of CTCs were highly different even for the same patient at different time points, and always increased before the clinical relapse. Our results indicate that liquid biopsy can reveal the presence of MRD at least 4 years before the appearance of clinically detectable metastatic disease demonstrating that a comprehensive liquid biopsy analysis provides highly important information for the therapeutic management of breast cancer patients.
Out-of-reach rewards elicit human-oriented referential communicative behaviours in family dogs but not in family pigs
Authors: Pérez Fraga Paula , Morvai Boglárka , Gerencsér Linda , Lehoczki Fanni , Andics Attila
Published: January 2023

Human-oriented referential communication has been evidenced not only in domestic but also in some wild species, however, the importance of domestication-unrelated species’ characteristics in the emergence of this capacity remains largely unexplored. One shared property of all species reported to exhibit referential communication is the efficient use of visual social signals. To assess the potential role of species-specific characteristics in the emergence of human-oriented referential communication, we compared similarly socialised companion animals from two domestic species: dogs, which rely heavily on conspecific visual social signals; and pigs, which do not. We used an out-of-reach reward paradigm with three conditions: both human and reward present, only human present, only reward present. Both species exhibited certain behaviours (e.g. orientation towards the human, orientation alternation between the human and the reward) more often in the human’s presence. However, only dogs exhibited those behaviours more often in the simultaneous presence of the human and the reward. These results suggest similar readiness in dogs and pigs to attend to humans but also that pigs, unlike dogs, do not initiate referential communication with humans. The ability to referentially communicate with humans may not emerge in mammals, even if domesticated companion animals, that lack certain species characteristics, such as efficient intraspecific visual communication.
Association of metallothionein 2A rs10636 with low mean corpuscular volume (MCV), low mean corpuscular haemoglobin (MCH) in healthy Taiwanese
Authors: Chen Rong-Fu , Chen Po-Ming , Pan Chau-Shiung , Huang Chieh-Cheng , Chiang En-Pei Isabel
Published: January 2023

Human metallothionein-2A (MT2A) protein participates in metal homeostasis, detoxification, oxidative stress reduction, and immune defense. It decreases heavy metal ions and reactive oxygen species (ROS) during injury of cells and tissues. The single nucleotide polymorphisms at the MT2A gene have been associated in various human diseases including cancer. The current study aimed to elucidate associations between MT2A genotypes with the clinical, biochemical, and molecular characteristics that potentially related to lowered MT2A ex-pression. One hundred and forty-one healthy Taiwanese subjects were enrolled from Changhua Show-Chwan Memorial Hospital. Clinical, biochemical and molecular characteristics including the frequent minor allele SNPs, rs28366003 and rs10636, within the MT2A gene were determined. The genotype distribution of MT2A rs10636 fits the Hardy–Weinberg equilibrium. The significant associations with gradually decline of mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) were identified with MT2A rs10636 and rs28366003 using analysis of variance (ANOVA) with Tukey’s analysis as a post hoc test. We further validated the correlations between the expressions of genes in erythropoiesis, cholesterol synthesis, platelet synthesis, insulin with MT2A using the web-based Gene Expression Profiling Interactive Analysis (GEPIA) databases. The results revealed that hypoxia-inducible factor 1α (HIF-1α), erythropoietin (EPO), lipoprotein lipase (LPL), and lecithin-cholesterol acyltransferase (LCAT) mRNA ex-pression are significantly correlated with MT2A mRNA expression. In conclusion, these results suggested that genetic variations of MT2A rs10636 and rs28366003 might be an important risk factor for erythropoiesis in the Taiwanese general population.
Influence of variability in the cyclooxygenase pathway on cardiovascular outcomes of nephrosclerosis patients
Authors: González Luz M. , Robles Nicolás R. , Mota-Zamorano Sonia , Valdivielso José M. , González-Rodríguez Laura , López-Gómez Juan , Gervasini Guillermo
Published: January 2023

Nephrosclerosis patients are at an exceptionally high cardiovascular (CV) risk. We aimed to determine whether genetic variability represented by 38 tag-SNPs in genes of the cyclooxygenase pathway (PTGS1, PTGS2, PTGES, PTGES2 and PTGES3) leading to prostaglandin E2 (PGE2) synthesis, modified CV traits and events in 493 nephrosclerosis patients. Additionally, we genotyped 716 controls to identify nephrosclerosis risk associations. The addition of three variants, namely PTGS2 rs4648268, PTGES3 rs2958155 and PTGES3 rs11300958, to a predictive model for CV events containing classic risk factors in nephrosclerosis patients, significantly enhanced its statistical power (AUC value increased from 78.6 to 87.4%, p = 0.0003). Such increase remained significant after correcting for multiple testing. In addition, two tag-SNPs (rs11790782 and rs2241270) in PTGES were linked to higher systolic and diastolic pressure [carriers vs. non-carriers = 5.23 (1.87–9.93), p = 0.03 and 5.9 (1.87–9.93), p = 0.004]. PTGS1(COX1) rs10306194 was associated with higher common carotid intima media thickness (ccIMT) progression [OR 1.90 (1.07–3.36), p = 0.029], presence of carotid plaque [OR 1.79 (1.06–3.01), p = 0.026] and atherosclerosis severity (p = 0.041). These associations, however, did not survive Bonferroni correction of the data. Our findings highlight the importance of the route leading to PGE2 synthesis in the CV risk experienced by nephrosclerosis patients and add to the growing body of evidence pointing out the PGE2 synthesis/activity axis as a promising therapeutic target in this field.
Incidence and impact of new-onset postoperative arrhythmia after surgery of the lower gastrointestinal tract
Authors: Rühlmann Felix , Hedicke Mara Sophie , Engelhardt Deborah , Mackert Alma Franziska , Tichelbäcker Tobias , Leha Andreas , Bernhardt Markus , Ghadimi Michael , Perl Thorsten , Azizian Azadeh , Gaedcke Jochen
Published: January 2023

Postoperative arrhythmias (PAs) are common events and have been widely investigated in cardiothoracic surgery. Within visceral surgery, a recent study revealed a significant occurrence of PA in esophageal resections. In contrast, PA in lower gastrointestinal surgery is rarely investigated and has been rudimentary described in the medical literature. The present work is a retrospective cohort study of 1171 patients who underwent surgery of lower gastrointestinal tract between 2012 and 2018. All included patients were treated and monitored in the intensive care unit (ICU) or intermediate care unit (IMC) after surgery. Follow-up, performed between January and May 2021, was obtained for the patients with PA investigating the possible persistence of PA and complications such as permanent arrhythmia or thromboembolic events after discharge. In total, n = 1171 patients (559 female, 612 male) without any history of prior arrhythmia were analyzed. Overall, PA occurred in n = 56 (4.8%) patients after surgery of the lower GI. The highest incidence of PA was seen in patients undergoing bowel surgery after mesenteric ischaemia (26.92%), followed by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC; 16.67%). PA was significantly associated with higher age (72 years (IQR 63–78 years) vs. 64 years (IQR 55–73.5 years), p < 0.001) and longer length of stay in the ICU (median 15 days (IQR 5–25 days) vs. median 2 days (IQR 1–5 days), p < 0.001). PA was independently associated with organ failure (OR = 4.62, 95% CI 2.11–10.11, p < 0.001) and higher in-house mortality (OR = 3.37, 95% CI 1.23–9.28, p < 0.001). In median, PA occurred 66.5 h after surgery. In follow-up, 31% of all the patients with PA showed development of permanent arrhythmia. The incidence of PA after lower GI surgery is comparatively low. Its occurrence, however, seems to have severe implications since it is significantly associated with higher rates of organ failure and in-house mortality. Also, compared to the general population, the development of permanent arrhythmia is significantly higher in patients who developed new-onset PA.
Mapping the diffusion pattern of 1O2 along DNA duplex by guanine photooxidation with an appended biphenyl photosensitizer
Authors: Kanamori Takashi , Kaneko Shota , Hamamoto Koji , Yuasa Hideya
Published: January 2023

To realize nucleic acid-targeting photodynamic therapy, a photosensitizer should be attached at the optimal position on a complementary oligonucleotide, where a guanine photooxidation is maximized. Here we show the photooxidation of 22 DNA duplexes with varied lengths between a1O2-generating biphenyl photosensitizer attached at a midchain thymine in a strand and the single guanine reactant in the other strand. The best photooxidation efficiencies are achieved at 9, 10, and 21 base intervals, which coincides with the pitch of 10.5 base pairs per turn in a DNA duplex. The low efficiencies for near and far guanines are due to quenching of the biphenyl by guanine and dilution of1O2by diffusion, respectively. The1O2-diffusion mapping along DNA duplex provides clues to the development of efficient and selective photosensitizer agents for nucleic acid-targeting photodynamic therapy, as well as an experimental demonstration of diffusion of a particle along cylindrical surface in molecular level.
Towards a high-density photonic tensor core enabled by intensity-modulated microrings and photonic wire bonding
Authors: Luan Enxiao , Yu Shangxuan , Salmani Mahsa , Nezami Mohammadreza Sanadgol , Shastri Bhavin J. , Chrostowski Lukas , Eshaghi Armaghan
Published: January 2023

We propose a photonic processing unit for high-density analog computation using intensity-modulation-based microring modulators (IM-MRMs). The output signal at the fixed resonance wavelength is directly intensity modulated by changing the extinction ratio (ER) of the IM-MRM . Thanks to the intensity-modulated approach, the proposed photonic processing unit is less sensitive to the inter-channel crosstalk. Simulation results reveal that the proposed design offers a maximum of 17-fold increase in wavelength channel density compared to its wavelength-modulated counterpart. Therefore, a photonic tensor core of size 512 $$\times $$
×
512 can be realized by current foundry lines. A convolutional neural network (CNN) simulator with 6-bit precision is built for handwritten digit recognition task using the proposed modulator. Simulation results show an overall accuracy of 96.76%, when the wavelength channel spacing suffers a 3-dB power penalty. To experimentally validate the system, 1000 dot product operations are carried out with a 4-bit signed system on a co-packaged photonic chip, where optical and electrical I/Os are realized using photonic and electrical wire bonding techniques. Study of the measurement results show a mean squared error (MSE) of 3.09$$\times $$
×
10$$^{-3}$$

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3

for dot product calculations. The proposed IM-MRM, therefore, renders the crosstalk issue tractable and provides a solution for the development of large-scale optical information processing systems with multiple wavelengths.