bluuebunny/crossref_metadata_2025 huggingface dataset:
Struggles for Power in the Kingdom of Italy
Authors: Manarini Edoardo
Published: April 2022

This book presents a detailed study which focuses upon the Hucpoldings, an elite group in Carolingian and post-Carolingian Italy. Though the Hucpoldings have not received extensive treatment in previous Anglophone scholarship, they are a key clan in this period. Manarini's ground-breaking study uses this kinship group to highlight and pinpoint the dramatic geopolitical changes in the kingdom of Italy across three crucial centuries. The research deals with the reconstruction of the political events of every identifiable member of the kinship, as well as the inquiry into their patrimony and their networks of relations and patronage throughout the kingdom of Italy. Finally, it examines the particular elements of the group, from which emerges a clearer picture of the nature of their power, their memory strategies and the shared perceptions and self-awareness among the group members.
Archaeological Approaches to and Heritage Perspectives on Modern Conflict
Authors: van der Schriek Max
Published: April 2022

From a wider disciplinary perspective, modern conflict archaeology is now a thoroughly established and mature sub-discipline. However, a significant problem that conflict archaeologists in the Netherlands face is that modern eras, including both World Wars, have so far not received serious attention. Although both World Wars appeal strongly to the popular imagination, until recently Dutch researchers had not approached modern conflict from an academic archaeological perspective to any great extent. This is partly the result of problematic legislation on archaeological activity in the Netherlands. When applied and interpreted appropriately, archaeology can play an important role in the preservation, contemporary experience and historical reconstruction of recent conflicts. However, as this book argues, research methods other than excavations will be needed in order to conduct conflict archaeology in the Netherlands effectively. This study aims to develop a Dutch approach to conflict archaeology, integrating archaeology, heritage research and history at a landscape scale.
Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them
Authors: So Miranda , Tsai Helen , Swaminathan Neeraja , Bartash Rachel
Published: April 2022

Antimicrobial therapies are essential tools for transplant recipients who are at high risk for infectious complications. However, judicious use of antimicrobials is critical to preventing the development of antimicrobial resistance. Treatment of multidrug-resistant organisms is challenging and potentially leads to therapies with higher toxicities, intravenous access, and intensive drug monitoring for interactions. Antimicrobial stewardship programs are crucial in the prevention of antimicrobial resistance, though balancing these strategies with the need for early and frequent antibiotic therapy in these immunocompromised patients can be challenging. In this review, we summarize 5 frequently encountered transplant infectious disease stewardship challenges, and we suggest strategies to improve practices for each clinical syndrome. These 5 challenging areas are: asymptomatic bacteriuria in kidney transplant recipients, febrile neutropenia in hematopoietic stem cell transplantation, antifungal prophylaxis in liver and lung transplantation, treatment of left-ventricular assist device infections, andClostridioides difficileinfection in solid-organ and hematopoietic stem-cell transplant recipients. Common themes contributing to these challenges include limited data specific to transplant patients, shortcomings in diagnostic testing, and uncertainties in pharmacotherapy.
Scaling laws for drag-to-thrust transition and propulsive performance in pitching flexible plates
Authors: Peng Ze-Rui , Sun Yuehao , Yang Dan , Xiong Yongliang , Wang Lei , Wang Lin
Published: April 2022

The propulsion of a pitching flexible plate in a uniform flow is investigated numerically. The effects of bending stiffness (

$K$

), pitching amplitude (

$A_L$

) and frequency (

$St$

) on the wake patterns, thrust generations and propulsive performances of the fluid–plate system are analysed. Four typical wake patterns, i.e. von Kármán, reversed von Kármán, deflected and chaotic wakes, emerge from various kinematics, and the

$St-A_L$

wake maps are given for various

$K$

. The drag-to-thrust transitions (DTT) and the wake transitions (WT) between the von Kármán and reversed von Kármán wakes are examined. Results indicate that the WT and DTT boundaries can be scaled by the chord-averaged distance of travel,

$\mathcal {L}$

, which leads to

$\mathcal {L}\times St \approx 1$

and

$\mathcal {L}\times St \approx 1.2$

, respectively. Further, the resonance mechanism for the performance enhancement is revealed and confirmed in a wide range of parameters. The dimensionless average speed of plate,

$\mathcal {U^*}\left (=\mathcal {L}\times St\right )$

, is adopted merely to characterize the propulsive performances. For the first time, the

$\mathcal {U^*}$

-based scaling laws for the thrust and power are revealed in pitching rigid and flexible plates for various

$A_L$

and

$St$

. This study may deepen our understanding of biological swimming and flying, and provide a guide for bionic design.
Association between protein intake and lean body mass in a group of Masters Athletes
Authors: Stanzione Joseph R. , Boullata Joseph I. , Bruneau Michael L. , Volpe Stella L.
Published: April 2022

Recommendations for protein intake are based on total body weight; however, these recommendations do not consider lean body mass (LBM). The purpose of the present study was to identify the average protein intake in g/kg LBM in a group of healthy Masters Athletes (≥26 years of age, exercising ≥2 d/week). Data were obtained from a cross-sectional study. Body weight (kg), height (cm) and LBM via dual-energy X-ray absorptiometry were measured. Dietary intake was measured using a 2005 Block Food Frequency Questionnaire. The average energy intake, the percent energy from protein and the average protein intake in g/kg LBM were calculated. Differences between protein intake and the US Recommended Dietary Allowance (US RDA) (0⋅8 g/kg body weight) were determined. Alpha levels were set a priori to P < 0⋅05. A total of 176 participants (94 women, 82 men; 39 ± 11 years of age; body mass index: 24⋅6 ± 3⋅4 kg/m2) were analysed. The average energy intake, the percent protein energy and the average protein intake were 7996⋅9 ± 110⋅9 kilojoules (kJ)/d (1,910⋅4 ± 26⋅5 kcal), 15⋅5 ± 2⋅6 % and 1⋅43 ± 0⋅53 g/kg LBM, respectively. No differences existed between women and men for protein intake/kg LBM. Both sexes had significantly higher protein intakes than the US RDA (P < 0⋅001). We identified the average protein intake (g/kg LBM) in healthy Masters Athletes that may contribute to evolving perspectives on the determination of protein needs. The present study helps establish the relationship between protein intake and LBM so that we may further increase our accuracy when developing future protein recommendations.
AMS Radiocarbon Date for Precolumbian Caribbean Rock Art: Borbón Cave No. 1, Dominican Republic
Authors: García-Diez Marcos , López Adolfo , Sarró Moreno Isabel , Fatás Monforte Pilar
Published: April 2022

We present an AMS radiocarbon date from a bird image in a cave on the island of Hispaniola in the northern Caribbean. Borbón Cave No. 1 contains a key rock art assemblage that likely reflects a significant part of past native Taíno societies’ symbolic thought and beliefs. The grouping has already served to define one rock art style in the Antilles: the Borbón School. Our sample yielded a date of 890 ± 30 BP (1045–1225 cal AD). This result, as well as additional published dates for the region, confirms that these images were created before European contact with the region. Further dating comparison indicates that Taíno artistic traditions persisted for some years after the arrival and settlement of Spanish colonists on the island.
Coal versus Coral
Authors: Konkes Claire , Nixon Cynthia , Lester Libby , Williams Kathleen
Published: April 2022

The likelihood that climate change may destroy the Great Barrier Reef has been a central motif in Australia’s climate change politics for more than a decade as political ideologies and corporate and environmental activism draw or refute connections between the coal industry and climate change. The media fuel this debate because in this contest, as ever, the news media always do more than simply report the news. Given that the Reef has also been central to the evolution of Australia’s environmental laws since the 1960s, it is not surprising that the Reef is now a leading actor in efforts to test the capacity of our environmental laws to support action on climate change. In this contribution, we examine the news coverage of the Australian Conservation Foundation’s (ACF) 2015 challenge to Adani’s Carmichael coal mine to observe the discursive struggle between the supporters and opponents of the mine. Our analysis of the case shows that while the courts are arenas of material and symbolic contest in the politics of climate change in Australia, public interest environmental litigants struggle both inside and outside the courts to challenge the privileging of mining interests over the public interest.
Drawing a Line in the Sand
Authors: Wodak Josh
Published: April 2022

What conservation could possibly become commensurate with the rates of human-induced biophysical change unfolding at the advent to the Sixth Extinction Event? Any such conservation would require time-critical interventions into both ecosystems and evolution itself, for these interventions would also require domains of risk and ethics that shatter normative understandings of conservation. Yet a line appears to have been drawn in the sand against such experimental conservation. Holding the line will retain conservation practices that are null and void against the extinction debt facing multitudes of species. Crossing the line would invoke scales of bioengineering that appear abhorrent to normative morality. This article explores the question of whether this line in the sand could, and should, be crossed through a detailed case study of current and proposed conservation for endangered Chelonia mydas sea turtles on Raine Island, a small coral cay on the Great Barrier Reef in Australia. Chelonia mydas and Raine Island are presented as synecdoche for conservation across diverse species across the world because turtles are among the most endangered of all reptiles and Raine Island is the largest and most important rookery in the world for this species. With such lines disappearing under the rising seas, the article contemplates the unthinkable questions that our current situation demands we ask, and perhaps even try to answer.
Self-perceptions of ageing and perceived health status: the mediating role of cognitive functioning and physical activity
Authors: Fernández-Jiménez Carolina , Dumitrache Cristina G. , Rubio Laura , Ruiz-Montero Pedro J.
Published: April 2022

There is evidence that perceived health status is relevant for older adults' wellbeing, and at the same time perceived health status can be influenced by self-perceptions of ageing. There is a lack of studies on the relationship between these variables. The aim of this study was to explore attitudes towards ageing and self-perceptions of ageing among Spanish middle-aged and older people, and to identify possible mediators in the relationship between self-perceptions of ageing on perceived health status. The sample comprised 1,124 individuals from 50 to 98 years old (mean = 64.84, standard deviation = 10.12) from the Ageing in Spain Longitudinal Study database, Pilot Survey (ELES-PS). Almost 70 per cent of the participants stated that old age begins at a specific chronological age and half of them considered that society treats older people with indifference. Self-perceptions of ageing, physical activity, cognitive functioning and age were significant predictors, and together these variables explained 15.9 per cent in the variance of perceived health status. The multiple mediation analysis revealed that self-perceptions of ageing predicted cognitive functioning (B = 0.848, p < 0.01) and physical activity (B = 2.9046, p < 0.001), and mediated the association between self-perceptions of ageing and perceived health status (B = 0.1144, standard error = 0.0147, p < 0.01). Results from this study highlight the importance of perceptions and attitudes towards ageing for older adults' health and wellbeing, thus this study contributes to a better understanding of how these variables are related. In this sense, results from this study can be useful for designing interventions for fostering wellbeing. Addressing negative self-perceptions of ageing and negative attitudes towards ageing can be particularly useful because they are associated with more pessimistic expectancies about the ageing process.
Spatial meta-analysis of the occurrence and distribution of tsetse-transmitted animal trypanosomiasis in Cameroon over the last 30 years
Authors: Sevidzem Silas Lendzele , Koumba Aubin Armel , Mavoungou Jacques François , Windsor Peter Andrew
Published: April 2022

In Cameroon, >90% of cattle are considered exposed to African animal trypanosomiasis (AAT) infection, with the presence of tsetse rendering cattle husbandry as a very difficult proposition. A systematic review of data on AAT and tsetse from 1990 to 2021 was conducted to develop a national atlas. The review identified 74 relevant scientific documents, with three pathogenic Trypanosoma species (Trypanosoma vivax, T. congolense and T. brucei s.l.) most frequently identified as causing AAT. Trypanosoma grayi, T. theileri, T. simiae and the human African trypanosomiasis causative agent T. brucei gambiense were also identified in a wide range of hosts. The tsetse fly fauna of Cameroon comprises nine species, with Glossina palpalis palpalis and G. fuscipes fuscipes the most widely distributed following their identification in seven and five of the 10 regions, respectively. Two species, Glossina nigrofusca and G. pallicera pallicera appeared to be rare and were restricted to both forest and protected areas. The presence of AAT is associated with the presence of tsetse in the livestock–human–wildlife interface of Cameroon. AAT occurs beyond the tsetse belts of the country where mechanical vectors are abundant. This study provides AAT and tsetse maps to support ongoing interventions in Cameroon.
Development of a millimeter-wave transparent antenna inside a headlamp for automotive radar application
Authors: Hamid Sofian , Heberling Dirk , Junghähnel Manuela , Preussner Thomas , Gretzki Patrick , Pongratz Ludwig , Hördemann Christian , Gillner Arnold
Published: April 2022

The development of a millimeter-wave transparent antenna integrated inside a headlamp for automotive radar application is presented. The antenna consists of two radiating elements: the primary and secondary ones. The primary antenna is the one that is fabricated on RF PCB material (e.g., patch, slot, sectoral horn) and connected directly to the transceiver chip, while the secondary antenna is made of optically transparent materials such as glass, but with a optical transparent electrically conductive coating, well known as transparent conductive oxide (TCO). This antenna is realized as a planar offset reflector to collimate and shape the incoming wave from the primary antenna. This reflector is designed based on the Fresnel theory and the reflectarray concept. The division of the primary and secondary antenna enables the placement of the radar module (that contains the primary antenna) at the base of the headlamp, and therefore it is concealed from the surroundings and hidden from the optical path of the light. The secondary antenna is inserted in the space between the headlamp cover and the light unit. The main challenge here is to provide a maximum on transparency in the visible range of the spectrum with a specially designed and laser-based generated microstructure for the resonant reflection of the radar wavelength. An antenna demonstrator has been fabricated, and together with the headlamp cover, the radiation pattern and realized gain are measured. We reported here the measurement results for several reflector designs and concluded that the headlamp cover gives minimal influence on the antenna performance.
Emotionally Toned Online Discussions Evoke Subjectively Experienced	Emotional Responses
Authors: Syrjämäki Aleksi H. , Ilves Mirja , Isokoski Poika , Kiskola Joel , Rantasila Anna , Olsson Thomas , Bente Gary , Surakka Veikko
Published: April 2022

Abstract. Emotions are an important element of human interactions, including those in social media. Despite the prominence of text-based messages in online communication, little is known about how the emotional tone of the messages affects the emotions of the recipients. With three experiments, the current study investigated these effects in the context of online news discussions. Participants first read news discussion threads with a negative, neutral, and positive tone, and then rated their subjective emotional state in terms of valence and arousal. Results showed that negatively toned discussions induced more negative valence and higher arousal ratings than the other conditions. Positive discussions had an opposite effect. Emotionally toned online comments evidently affect the quality and the intensity of the readers’ subjective emotions. We discuss implications for future research and emotion mitigation strategies to improve online discussion quality.
Subsurface Eddy Facilitates Retention of Simulated Diel Vertical Migrators in a Biological Hotspot
Authors: Hudson K. , Oliver M. J. , Kohut J. , Cohen J. H. , Dinniman M. S. , Klinck J. M. , Reiss C. S. , Cutter G. R. , Statscewich H. , Bernard K. S. , Fraser W.
Published: April 2022

Diel vertical migration (DVM) is common in zooplankton populations worldwide. Every day, zooplankton leave the productive surface ocean and migrate to deepwater to avoid visual predators and return to the surface at night to feed. This behavior may also help retain migrating zooplankton in biological hotspots. Compared to fast and variable surface currents, deep ocean currents are sluggish, and can be more consistent. The time spent in the subsurface layer is driven by day length and the depth of the surface mixed layer. A subsurface, recirculating eddy has recently been described in Palmer Deep Canyon (PDC), a submarine canyon in a biological hotspot located adjacent to the West Antarctic Peninsula. Circulation model simulations have shown that residence times of neutrally buoyant particles increase with depth within this feature. We hypothesize that DVM into the subsurface eddy increases local retention of migrating zooplankton in this feature and that shallow mixed layers and longer days increase residence times. We demonstrate that simulated vertically migrating zooplankton can have residence times on the order of 30 days over the canyon, which is five times greater than residence times of near‐surface, nonmigrating zooplankton within PDC and other adjacent coastal regions. The potential interaction of zooplankton with this subsurface feature may be important to the establishment of the biological hotspot around PDC by retaining food resources in the region. Acoustic field observations confirm the presence of vertical migrators in this region, suggesting that zooplankton retention due to the subsurface eddy is feasible.
Thermohydrological Impact of Forest Disturbances on Ecosystem‐Protected Permafrost
Authors: Stuenzi Simone Maria , Kruse Stefan , Boike Julia , Herzschuh Ulrike , Oehme Alexander , Pestryakova Luidmila A. , Westermann Sebastian , Langer Moritz
Published: April 2022

Boreal forests cover over half of the global permafrost area and protect underlying permafrost. Boreal forest development, therefore, has an impact on permafrost evolution, especially under a warming climate. Forest disturbances and changing climate conditions cause vegetation shifts and potentially destabilize the carbon stored within the vegetation and permafrost. Disturbed permafrost‐forest ecosystems can develop into a dry or swampy bush‐ or grasslands, shift toward broadleaf‐ or evergreen needleleaf‐dominated forests, or recover to the pre‐disturbance state. An increase in the number and intensity of fires, as well as intensified logging activities, could lead to a partial or complete ecosystem and permafrost degradation. We study the impact of forest disturbances (logging, surface, and canopy fires) on the thermal and hydrological permafrost conditions and ecosystem resilience. We use a dynamic multilayer canopy‐permafrost model to simulate different scenarios at a study site in eastern Siberia. We implement expected mortality, defoliation, and ground surface changes and analyze the interplay between forest recovery and permafrost. We find that forest loss induces soil drying of up to 44%, leading to lower active layer thicknesses and abrupt or steady decline of a larch forest, depending on disturbance intensity. Only after surface fires, the most common disturbances, inducing low mortality rates, forests can recover and overpass pre‐disturbance leaf area index values. We find that the trajectory of larch forests after surface fires is dependent on the precipitation conditions in the years after the disturbance. Dryer years can drastically change the direction of the larch forest development within the studied period.
Decoy receptor 3 is involved in epidermal keratinocyte commitment to terminal differentiation via EGFR and PKC activation
Authors: Wu Nan-Lin , Huang Duen-Yi , Hsieh Shie-Liang , Dai Yang-Shia , Lin Wan-Wan
Published: April 2022

Decoy receptor 3 (DcR3) is a soluble receptor for Fas ligand, LIGHT and TL1A, but it also exerts effector functions. Previously, we found that DcR3 is upregulated in the serum and lesional skin of patients with psoriasis and is upregulated by EGFR activation in proliferating primary human epidermal keratinocytes. However, the functional role of intracellular DcR3 in keratinocyte differentiation is still incompletely defined. Herein, primary cultured human epidermal keratinocytes were differentiated by phorbol 12-myristate 13-acetate (PMA) treatment, calcium treatment and cell confluence, which are three standard in vitro differentiation models. We found that the constitutive expression of the DcR3 gene and protein was progressively suppressed during terminal differentiation of keratinocytes. These changes were correlated with downregulation of EGFR activation during keratinocyte differentiation. EGFR inhibition by gefitinib further decreased confluence-induced suppression of DcR3 mRNA expression, and, vice versa, knocking down DcR3 expression attenuated EGFR and EGFR ligand expression as well as EGFR activation. Under conditions without a change in cell growth, DcR3 silencing reduced the expression of involucrin and transglutaminase 1 but enhanced the induction of the terminal differentiation markers keratin 10 and loricrin. Of note, DcR3 interacted with PKCα and PKCδ and enhanced PKC activity. In keratinocytes with PKCα and PKCδ silencing, differentiation markers were differentially affected. In conclusion, DcR3 expression in keratinocytes is regulated by EGFR and forms a positive feedback loop to orchestrate constitutive EGFR and PKC activity. During differentiation, DcR3 is downregulated and involved in modulating the pattern of terminal differentiation.
Structure and density of silicon carbide to 1.5 TPa and implications for extrasolar planets
Authors: Kim D. , Smith R. F. , Ocampo I. K. , Coppari F. , Marshall M. C. , Ginnane M. K. , Wicks J. K. , Tracy S. J. , Millot M. , Lazicki A. , Rygg J. R. , Eggert J. H. , Duffy T. S.
Published: April 2022

There has been considerable recent interest in the high-pressure behavior of silicon carbide, a potential major constituent of carbon-rich exoplanets. In this work, the atomic-level structure of SiC was determined through in situ X-ray diffraction under laser-driven ramp compression up to 1.5 TPa; stresses more than seven times greater than previous static and shock data. Here we show that the B1-type structure persists over this stress range and we have constrained its equation of state (EOS). Using this data we have determined the first experimentally based mass-radius curves for a hypothetical pure SiC planet. Interior structure models are constructed for planets consisting of a SiC-rich mantle and iron-rich core. Carbide planets are found to be ~10% less dense than corresponding terrestrial planets.
Peptidoglycan biosynthesis is driven by lipid transfer along enzyme-substrate affinity gradients
Authors: Oluwole Abraham O. , Corey Robin A. , Brown Chelsea M. , Hernández-Rocamora Victor M. , Stansfeld Phillip J. , Vollmer Waldemar , Bolla Jani R. , Robinson Carol V.
Published: April 2022

Maintenance of bacterial cell shape and resistance to osmotic stress by the peptidoglycan (PG) renders PG biosynthetic enzymes and precursors attractive targets for combating bacterial infections. Here, by applying native mass spectrometry, we elucidate the effects of lipid substrates on the PG membrane enzymes MraY, MurG, and MurJ. We show that dimerization of MraY is coupled with binding of the carrier lipid substrate undecaprenyl phosphate (C55-P). Further, we demonstrate the use of native MS for biosynthetic reaction monitoring and find that the passage of substrates and products is controlled by the relative binding affinities of the different membrane enzymes. Overall, we provide a molecular view of how PG membrane enzymes convey lipid precursors through favourable binding events and highlight possible opportunities for intervention.
Data-driven capacity estimation of commercial lithium-ion batteries from voltage relaxation
Authors: Zhu Jiangong , Wang Yixiu , Huang Yuan , Bhushan Gopaluni R. , Cao Yankai , Heere Michael , Mühlbauer Martin J. , Mereacre Liuda , Dai Haifeng , Liu Xinhua , Senyshyn Anatoliy , Wei Xuezhe , Knapp Michael , Ehrenberg Helmut
Published: April 2022

Accurate capacity estimation is crucial for the reliable and safe operation of lithium-ion batteries. In particular, exploiting the relaxation voltage curve features could enable battery capacity estimation without additional cycling information. Here, we report the study of three datasets comprising 130 commercial lithium-ion cells cycled under various conditions to evaluate the capacity estimation approach. One dataset is collected for model building from batteries with LiNi0.86Co0.11Al0.03O2-based positive electrodes. The other two datasets, used for validation, are obtained from batteries with LiNi0.83Co0.11Mn0.07O2-based positive electrodes and batteries with the blend of Li(NiCoMn)O2- Li(NiCoAl)O2positive electrodes. Base models that use machine learning methods are employed to estimate the battery capacity using features derived from the relaxation voltage profiles. The best model achieves a root-mean-square error of 1.1% for the dataset used for the model building. A transfer learning model is then developed by adding a featured linear transformation to the base model. This extended model achieves a root-mean-square error of less than 1.7% on the datasets used for the model validation, indicating the successful applicability of the capacity estimation approach utilizing cell voltage relaxation.
Safety and serum distribution of anti-SARS-CoV-2 monoclonal antibody MAD0004J08 after intramuscular injection
Authors: Lanini Simone , Milleri Stefano , Andreano Emanuele , Nosari Sarah , Paciello Ida , Piccini Giulia , Gentili Alessandra , Phogat Adhuna , Hyseni Inesa , Leonardi Margherita , Torelli Alessandro , Montomoli Emanuele , Paolini Andrea , Frosini Andrea , Antinori Andrea , Nicastri Emanuele , Girardi Enrico , Plazzi Maria Maddalena , Ippolito Giuseppe , Vaia Francesco , Della Cioppa Giovanni , Rappuoli Rino
Published: April 2022

The emerging threat represented by SARS-CoV-2 variants, demands the development of therapies for better clinical management of COVID-19. MAD0004J08 is a potent Fc-engineered monoclonal antibody (mAb) able to neutralize in vitro all current SARS-CoV-2 variants of concern (VoCs) including the omicron variant even if with significantly reduced potency. Here we evaluated data obtained from the first 30 days of a phase 1 clinical study (EudraCT N.: 2020-005469-15 and ClinicalTrials.gov Identifier: NCT04932850). The primary endpoint evaluated the percentage of severe adverse events. Secondary endpoints evaluated pharmacokinetic and serum neutralization titers. A single dose administration of MAD0004J08 via intramuscular (i.m.) route is safe and well tolerated, resulting in rapid serum distribution and sera neutralizing titers higher than COVID-19 convalescent and vaccinated subjects. A single dose administration of MAD0004J08 is also sufficient to effectively neutralize major SARS-CoV-2 variants of concern (alpha, beta, gamma and delta). MAD0004J08 can be a major advancement in the prophylaxis and clinical management of COVID-19.
A cryptic pocket in Ebola VP35 allosterically controls RNA binding
Authors: Cruz Matthew A. , Frederick Thomas E. , Mallimadugula Upasana L. , Singh Sukrit , Vithani Neha , Zimmerman Maxwell I. , Porter Justin R. , Moeder Katelyn E. , Amarasinghe Gaya K. , Bowman Gregory R.
Published: April 2022

Protein-protein and protein-nucleic acid interactions are often considered difficult drug targets because the surfaces involved lack obvious druggable pockets. Cryptic pockets could present opportunities for targeting these interactions, but identifying and exploiting these pockets remains challenging. Here, we apply a general pipeline for identifying cryptic pockets to the interferon inhibitory domain (IID) of Ebola virus viral protein 35 (VP35). VP35 plays multiple essential roles in Ebola’s replication cycle but lacks pockets that present obvious utility for drug design. Using adaptive sampling simulations and machine learning algorithms, we predict VP35 harbors a cryptic pocket that is allosterically coupled to a key dsRNA-binding interface. Thiol labeling experiments corroborate the predicted pocket and mutating the predicted allosteric network supports our model of allostery. Finally, covalent modifications that mimic drug binding allosterically disrupt dsRNA binding that is essential for immune evasion. Based on these results, we expect this pipeline will be applicable to other proteins.
ASCL1 activates neuronal stem cell-like lineage programming through remodeling of the chromatin landscape in prostate cancer
Authors: Nouruzi Shaghayegh , Ganguli Dwaipayan , Tabrizian Nakisa , Kobelev Maxim , Sivak Olena , Namekawa Takeshi , Thaper Daksh , Baca Sylvan C. , Freedman Matthew L. , Aguda Adeleke , Davies Alastair , Zoubeidi Amina
Published: April 2022

Treatment with androgen receptor pathway inhibitors (ARPIs) in prostate cancer leads to the emergence of resistant tumors characterized by lineage plasticity and differentiation toward neuroendocrine lineage. Here, we find that ARPIs induce a rapid epigenetic alteration mediated by large-scale chromatin remodeling to support activation of stem/neuronal transcriptional programs. We identify the proneuronal transcription factor ASCL1 motif to be enriched in hyper-accessible regions. ASCL1 acts as a driver of the lineage plastic, neuronal transcriptional program to support treatment resistance and neuroendocrine phenotype. Targeting ASCL1 switches the neuroendocrine lineage back to the luminal epithelial state. This effect is modulated by disruption of the polycomb repressive complex-2 through UHRF1/AMPK axis and change the chromatin architecture in favor of luminal phenotype. Our study provides insights into the epigenetic alterations induced by ARPIs, governed by ASCL1, provides a proof of principle of targeting ASCL1 to reverse neuroendocrine phenotype, support luminal conversion and re-addiction to ARPIs.
Superstretchable, yet stiff, fatigue-resistant ligament-like elastomers
Authors: Li Mengxue , Chen Lili , Li Yiran , Dai Xiaobin , Jin Zhekai , Zhang Yucheng , Feng Wenwen , Yan Li-Tang , Cao Yi , Wang Chao
Published: April 2022

Ligaments are flexible and stiff tissues around joints to support body movements, showing superior toughness and fatigue-resistance. Such a combination of mechanical properties is rarely seen in synthetic elastomers because stretchability, stiffness, toughness, and fatigue resistance are seemingly incompatible in materials design. Here we resolve this long-standing mismatch through a hierarchical crosslinking design. The obtained elastomer can endure 30,000% stretch and exhibit a Young’s modulus of 18 MPa and toughness of 228 MJ m−3, outperforming all the reported synthetic elastomers. Furthermore, the fatigue threshold is as high as 2,682 J m−2, the same order of magnitude as the ligaments (~1,000 J m−2). We reveal that the dynamic double-crosslinking network composed of Li+-O interactions and PMMA nanoaggregates allows for a hierarchical energy dissipation, enabling the elastomers as artificial ligaments in soft robotics.
USP14-regulated allostery of the human proteasome by time-resolved cryo-EM
Authors: Zhang Shuwen , Zou Shitao , Yin Deyao , Zhao Lihong , Finley Daniel , Wu Zhaolong , Mao Youdong
Published: April 2022

Proteasomal degradation of ubiquitylated proteins is tightly regulated at multiple levels1–3. A primary regulatory checkpoint is the removal of ubiquitin chains from substrates by the deubiquitylating enzyme ubiquitin-specific protease 14 (USP14), which reversibly binds the proteasome and confers the ability to edit and reject substrates. How USP14 is activated and regulates proteasome function remain unknown4–7. Here we present high-resolution cryo-electron microscopy structures of human USP14 in complex with the 26S proteasome in 13 distinct conformational states captured during degradation of polyubiquitylated proteins. Time-resolved cryo-electron microscopy analysis of the conformational continuum revealed two parallel pathways of proteasome state transitions induced by USP14, and captured transient conversion of substrate-engaged intermediates into substrate-inhibited intermediates. On the substrate-engaged pathway, ubiquitin-dependent activation of USP14 allosterically reprograms the conformational landscape of the AAA-ATPase motor and stimulates opening of the core particle gate8–10, enabling observation of a near-complete cycle of asymmetric ATP hydrolysis around the ATPase ring during processive substrate unfolding. Dynamic USP14–ATPase interactions decouple the ATPase activity from RPN11-catalysed deubiquitylation11–13 and kinetically introduce three regulatory checkpoints on the proteasome, at the steps of ubiquitin recognition, substrate translocation initiation and ubiquitin chain recycling. These findings provide insights into the complete functional cycle of the USP14-regulated proteasome and establish mechanistic foundations for the discovery of USP14-targeted therapies.
Reproducibility between three-dimensional turbo spin-echo and two-dimensional dual inversion recovery turbo spin-echo for coronary vessel wall imaging in Kawasaki disease
Authors: Matsumoto Koji , Yokota Hajime , Yoda Takafumi , Ebata Ryota , Mukai Hiroki , Masuda Yoshitada , Uno Takashi
Published: April 2022

Magnetic resonance vessel wall imaging is desirable for evaluating Kawasaki disease (KD)-associated coronary arterial lesions. To evaluate the reproducibility of three-dimensional turbo spin-echo (3D-TSE) and two-dimensional dual inversion-recovery turbo spin-echo (2D-DIR-TSE) for coronary vessel wall imaging in KD. Ten patients were prospectively enrolled. Coronary vessel wall imaging with axial-slice orientation 3D-TSE and 2D-DIR-TSE were acquired for cross-sectional images in aneurysmal and normal regions. Lumen area (LA), wall area (WA), and normalized wall index (NWI) of cross-sectional images were measured in both regions. Reproducibility between 3D-TSE and 2D-DIR-TSE was evaluated via intraclass correlation coefficients (ICCs) and Bland–Altman plots. 48 points (aneurysmal, 27; normal, 21) were evaluated. There were high ICCs between 3D-TSE and 2D-DIR-TSE in LA (0.95) and WA (0.95). In aneurysmal regions, 95% limits of agreement were LA, WA, and NWI of − 29.9 to 30.4 mm2, − 18.8 to 15.0 mm2, and − 0.22 to 0.20, respectively. In normal regions, the 95% limits of agreement were LA, WA, and NWI of − 4.44 to 4.38 mm2, − 3.51 to 4.30 mm2, and − 0.14 to 0.16, respectively. No fixed and proportional biases between 3D-TSE and 2D-DIR-TSE images in aneurysmal and normal regions were noted. 3D-TSE was reproducible with conventional 2D-DIR-TSE for coronary vessel wall assessment on KD.
Rice bran protein oxidation induced by rancidity alters the gut microbiota and intestinal permeability in mice
Authors: Li Fang , Kang Zhuoran , Wu Xiaojuan , Wu Wei
Published: April 2022

Oxidized RBP induced by rice bran rancidity changes the gut microbiota profile, slightly affects the production of SCFAs, and improves the intestinal barrier by upregulating the expression of tight junction proteins.
Gold nanocluster-based ratiometric fluorescent probe for biosensing of Hg2+ ions in living organisms
Authors: Yu Fanfan , Xiang Hui , He Shiyu , Zhao Gan , Cao Zheng , Yang Lina , Liu Honglin
Published: April 2022

A gold nanocluster-based dual-emission fluorescent nanoprobe for ratiometric sensing and imaging of Hg2+ ions in living organisms.
A conformational study of the 10–23 DNAzyme via programmed DNA self-assembly
Authors: Mao Dake , Li Qian , Li Qian , Wang Pengfei , Mao Chengde
Published: April 2022

We have developed a strategy to study the interhelical angle of two DNA duplexes in nucleic acids as exemplified by the 10–23 DNAzyme. The nucleic acids are programmed to assemble into large 2D arrays to reduce random conformation fluctuation and facilitate the conformation study.
Asymmetric total synthesis of prostaglandin C2 TBS ether
Authors: Yi Xiaofen , Long Xueyu , Chen Yu , Cen Xiangling , Tang Pei , Chen Fener
Published: April 2022

Asymmetric total synthesis of prostaglandin C2 TBS ether has been achieved via a stereoselective SmI2-mediated ketyl–enoate cyclization and a Grignard addition/dehydration/metathesis sequence.
A study to discover novel pharmaceutical cocrystals of pelubiprofen with a machine learning approach compared
Authors: Kim Paul , Lee In-Seo , Kim Ji-Yoon , Mswahili Medard E. , Jeong Young-Seob , Yoon Woo-Jin , Yun Ho-Seop , Lee Min-Jeong , Choi Guang J.
Published: April 2022

Pharmaceutical cocrystals of pelubiprofen (PF) were discovered for the first time. 16 candidates to form cocrystals with PF were selected via the ANN model and the pKa rule.
Coordination compound-derived La-doped FeS2/N-doped carbon (NC) as an efficient electrocatalyst for the oxygen evolution reaction
Authors: Ma Xuan Ao , Hai Yang , Gong Yun
Published: April 2022

By annealing/sulfuring [LaxFe1−x(H2O)8Fe(CN)6]·2hmt (hmt = hexamethylene-tetramine), the obtained La-doped FeS2/N-doped carbon (NC) shows excellent electrocatalytic activity for the oxygen evolution reaction.
Crystal structures, crystallization and II–I transition behaviors of iPB-1 in iPB-1/UHMWPE blends. Part 1. Crystal structures and crystallization behaviors
Authors: Liu Yuanxing , Li Jingqing
Published: April 2022

Blending with UHMWPE inhibits the overall melt crystallization kinetics of iPB-1 due to its spherulite nucleation density decrease in spite of the observed spherulite growth enhancement. It may provide a model system for II–I transition study.
Surface coverage of alcohols on carbon nanomembranes under ambient conditions
Authors: Khayya Neita , Gölzhäuser Armin , Dementyev Petr
Published: April 2022

A reference system is proposed to calibrate PM-IRAS measurements with vaporous substances.
Theoretical and experimental study of the microstructure of a metallic melt in an In50Bi50 alloy based on the Wulff cluster model
Authors: Shao Anchen , Tian Xuelei , Song Lin , Hua Minghao , Xue Jiajia , Wu Shuang , Lin Xiaohang
Published: April 2022

The Wulff cluster model has been extended to an alloy with intermetallic compounds (In50Bi50). The simulated XRD patterns are in good agreement with HTXRD results; the results near liquidus suggest that the nucleation of Bi clusters begins at 160 °C.
Vibrational mode analysis of hydrogen-bonded organic frameworks (HOFs): synchrotron infrared studies
Authors: Ennis Courtney , Appadoo Dominique R. T. , Boer Stephanie A. , White Nicholas G.
Published: April 2022

Vibrational analysis of hydrogen-bonded organic frameworks (HOFs). Characterisation of structure, morphology and host–guest properties using synchrotron infrared spectroscopy and periodic density functional theory.
Novel heterobimetallic Ir(iii)–Re(i) complexes: design, synthesis and antitumor mechanism investigation
Authors: Lu Jun-Jian , Ma Xiu-Rong , Xie Kai , Yang Pei-Xin , Li Rong-Tao , Ye Rui-Rong
Published: April 2022

Novel heterobimetallic Ir(iii)–Re(i) complexes can specifically image lysosomes, and induce apoptosis in HeLa cells through mitochondrial damage, caspase-3 activation and cell cycle arrest.
Highly emissive supramolecular gold(i)–BTD materials
Authors: Pinto Andrea , Echeverri Marcelo , Gómez-Lor Berta , Rodríguez Laura
Published: April 2022

Herein we report the synthesis of three light emitting rod-shaped gold(i) complexes by combining ethynyl-functionalized 2,1,3-benzothiadiazole (BTD), with different N-heterocyclic (imidazole, benzimidazole and phenantroimidazole) carbene gold(i) complexes.
Differential detection of strong acids in weak acids: a combination of a benzimidazole-carbazole backbone with AIE luminophores as highly sensitive and selective turn-on fluorescent probes
Authors: Lin Pei-Chi , Lin Yu-Ting , Liu Kuan-Ting , Chen Meng-Sin , Zhang Yong-Yun , Li Jie-Cheng , Leung Man-kit
Published: April 2022

With the combination of a benzimidazole-carbazole backbone and AIE luminophores, highly sensitive and selective turn-on fluorescent probes are achieved and applicable for differential detection of strong acids in weak acids.
Characteristic vibrational frequencies of osmium(ii) nitrosyl complexes probed by Raman spectroscopy and DFT calculations
Authors: Bélanger-Desmarais Nicolas , Gavriluta Anatolie , Tommasino Jean Bernard , Reber Christian , Luneau Dominique
Published: April 2022

Raman spectroscopy at variable temperature provides experimental frequencies for osmium(ii) nitrosyl complexes. Vibrational transitions are assigned using DFT calculations.
Scale-up and optimization of the synthesis of dual CBP/BRD4 inhibitor ISOX-DUAL
Authors: Edmonds Anthony K. , Oakes Catherine S. , Hassell-Hart Storm , Bruyère Didier , Tizzard Graham J. , Coles Simon J. , Felix Robert , Maple Hannah J. , Marsh Graham P. , Spencer John
Published: April 2022

A much improved synthesis, in significantly higher overall yield, for this important chemical probe is reported. Problematic steps have been revisited, closely examined and rectified.
Parallel imaging of coagulation pathway proteases activated protein C, thrombin, and factor Xa in human plasma
Authors: Modrzycka Sylwia , Kołt Sonia , Polderdijk Stéphanie G. I. , Adams Ty E. , Potoczek Stanisław , Huntington James A. , Kasperkiewicz Paulina , Drąg Marcin
Published: April 2022

Using a collection of natural and unnatural amino acids, we synthesized a set of fluorescent activity-based probes for the fast, direct, and simultaneous detection of coagulation factors in human plasma.
A visible light/heat responsive covalent organic framework for highly efficient and switchable proton conductivity
Authors: Chen Yongkui , Qiu Jikuan , Zhang Xia-Guang , Wang Huiyong , Yao Wenhui , Li Zhiyong , Xia Qingchun , Zhu Guangshan , Wang Jianji
Published: April 2022

A novel visible light/heat responsive 2D COF is designed and synthesized to achieve high proton conductivity (0.02 S cm−1), remarkable conductivity modulation (three orders of magnitude), and excellent recyclability (more than 20 cycles).
The SATPAC Approach and Remediation of Speech Sound Errors in an RTI Context: A Replication
Authors: Flipsen Peter , Sacks Stephen
Published: April 2022

Purpose:

This retrospective study was intended to replicate findings from Sacks et al. (2013) regarding the efficacy of using the SATPAC (Systematic Articulation Training Program Accessing Computers) approach for remediating speech sound errors in a Tier 3 response to intervention (RTI) context.

Method:

Nine children aged 7;7 (years;months) to 9;11 (eight boys, one girl) previously treated using the SATPAC approach within an RTI context who had exhibited consistent errors on one or two speech sounds were identified. Three others served as delayed-treatment controls. Eleven of the 12 children spoke another language in addition to English. Baseline data were available from a recording of Contextual Probes of Articulation Competence words and sentences. Treatment occurred once weekly for 15 min and was terminated either upon successful completion of the program or at the end of the school year. Each student received 1.25–7.75 total hours of treatment per speech sound target. Generalization to conversational speech was also measured.

Results:

Seven of nine students achieved at least 90% target accuracy in single words at the end of the treatment period. Six of the nine achieved at least 90% target accuracy in conversational speech at follow-up. The three delayed-treatment controls failed to complete the treatment program but exhibited greater and faster improvement during 8–9 weeks of treatment than during the 6-month no-treatment period. This suggested that the change observed for the majority of the participants was the result of the treatment provided.

Conclusions:

Consistent with Sacks et al. (2013), the SATPAC approach appeared to be efficacious for remediating single speech sound errors within an RTI context. It did so with a relatively brief amount (i.e., less than 5 hr on average) of treatment. Thus, it appears to represent a viable option for application to RTI.
Evidence of ram-pressure stripping of WLM, a dwarf galaxy far away from any large host galaxy
Authors: Yang Yanbin , Ianjamasimanana Roger , Hammer Francois , Higgs Clare , Namumba Brenda , Carignan Claude , Józsa Gyula I. G. , McConnachie Alan W.
Published: April 2022

Dwarf galaxies are affected by all the evolutionary processes normally at work in galaxies of any mass. As fainter and less massive galaxies, however, dwarf galaxies are particularly susceptible to environmental mechanisms that can more easily perturb these systems. Importantly, the presence of nearby large galaxies is expected to have a profound effect on dwarf galaxies. Gravitational (especially tidally induced) effects from the large galaxy can cause mass to be lost from the dwarf, and the passage of the dwarf through the gaseous medium surrounding the large galaxy can additionally cause the dwarf to lose its own gas through a process called ram-pressure stripping. Such effects are considered to be the main sources of difference between “satellite” and “field” dwarf galaxy populations. Here, we report on new observations of the gaseous content of Wolf–Lundmark–Melotte (WLM), an archetype of isolated, gas-rich field dwarf galaxies in the Local Universe, which presents a much more complex situation. Previous studies of its gaseous disk suggest it has perturbed kinematics; here, we identify four trailing, extended gas clouds lying in the direction opposite to WLM’s spatial motion, as well as a spatial offset between the WLM gas and stars. Overall, the morphology and kinematics of this gas show that WLM is undergoing ram-pressure stripping, despite being 930 and 830 kpc from the Milky Way and M 31, respectively. This finding indicates the presence of an intergalactic, gaseous reservoir far from large galaxies whose evolutionary role in galaxies, both large and small, may not be fully appreciated.