bluuebunny/crossref_metadata_2025 huggingface dataset:
Flexibel, stabil und effektiv? Zum Stand der Forschung über Minderheitsregierungen
Authors: Thürk Maria , Stecker Christian
Published: December 2023

Minderheitsregierungen stellen im internationalen Vergleich etwa ein Drittel aller Regierungen in etablierten parlamentarischen Demokratien dar. Insbesondere in den letzten beiden Jahrzehnten lässt sich international ein deutlicher Anstieg von Minderheitsregierungen feststellen. Während Minderheitsregierungen im deutschen Sprachraum oft kritisch betrachtet werden und üblicherweise nur als Notlösung in Ausnahmefällen gelten, sind sie in Skandinavien oder Neuseeland der reguläre Modus des Regierens. Im vorliegenden Literaturbericht wird der aktuelle Forschungsstand zum Regieren von Minderheitskabinetten sowohl auf nationaler als auch auf internationaler Ebene dargelegt. Zunächst wird erörtert, wie Minderheitsregierungen definiert werden und wo sie häufig anzutreffen sind. Anschließend beleuchtet der Bericht die Handlungskalküle von Parteien und erläutert, warum es für sie eine rationale Strategie sein kann, Minderheitsregierungen zu tolerieren, anstatt an der Regierung teilzunehmen. Weiterhin werden die institutionellen und situativen Bedingungen erläutert, unter denen die Bildung von Minderheitsregierungen wahrscheinlicher wird. Es werden auch die verschiedenen Möglichkeiten aufgezeigt, wie Minderheitsregierungen parlamentarische Mehrheiten für die Durchsetzung ihres Programms organisieren können. Abschließend wird die Performanz von Minderheitsregierungen diskutiert, wobei sowohl die Nachteile als auch die zahlreichen normativen Vorteile beleuchtet werden.
The adverse outcome pathway for breast cancer: a knowledge management framework bridging biomedicine and toxicology
Authors: von Coburg Elena , Dunst Sebastian
Published: December 2023

Breast cancer is the most common cancer worldwide, with an estimated 2.3 million new cases diagnosed every year. Effective measures for cancer prevention and cancer therapy require a detailed understanding of the individual key disease mechanisms involved and their interactions at the molecular, cellular, tissue, organ, and organism level. In that regard, the rapid progress of biomedical and toxicological research in recent years now allows the pursuit of new approaches based on non-animal methods that provide greater mechanistic insight than traditional animal models and therefore facilitate the development of Adverse Outcome Pathways (AOPs) for human diseases. We performed a systematic review of the current state of published knowledge with regard to breast cancer to identify relevant key mechanisms for inclusion into breast cancer AOPs, i.e. decreased cell stiffness and decreased cell adhesion, and to concurrently map non-animal methods addressing these key events. We conclude that the broader sharing of expertise and methods between biomedical research and toxicology enabled by the AOP knowledge management framework can help to coordinate global research efforts and accelerate the transition to advanced non-animal methods, which, when combined into powerful method batteries, closely mimic human physiology and disease states without the need for animal testing.
Multiple Hypointense Vessels are Associated with Cognitive Impairment in Patients with Single Subcortical Infarction
Authors: Yang Tang , Peng Pengfei , Jiang Shuai , Yan Yuying , Hu Yi , Wang Hang , Ye Chen , Pan Ruosu , Sun Jiayu , Wu Bo
Published: December 2023

We aimed to explore the relationship between multiple hypointense vessels and cognitive function in patients with single subcortical infarction (SSI) and the role of SSI with different etiological mechanisms in the above relationship. Multiple hypointense vessels were measured by the number of deep medullary veins (DMVs), DMVs score, and cortical veins (CVs) score. The Montreal Cognitive Assessment (MoCA), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) were assessed to evaluate cognitive function. SSI was dichotomized as branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI by whole-brain vessel-wall magnetic resonance imaging. We included a total of 103 acute SSI patients. After adjustments were made for related risk factors of cognitive function, the SSI patients with higher DMVs score were more likely to have longer STT-B (P = 0.001) and smaller STT-B-1 min (P = 0.014), and the SSI patients with higher CVs score were more likely to have shorter STT-A (P = 0.049). In subgroup analysis, we found that the negative relationship between DMVs scores and cognitive function and the positive relationship between CVs scores and cognitive function were significantly stronger in BAD patients. We provided valuable insights into the associations between DMVs, CVs, and multi-domain cognitive impairment in SSI patients, which underscored the necessity to further study the dynamic alterations of venules and their specific influence on post-stroke cognitive impairment.
Machine learning techniques to predict the risk of developing diabetic nephropathy: a literature review
Authors: Mesquita F. , Bernardino J. , Henriques J. , Raposo JF. , Ribeiro RT. , Paredes S.
Published: December 2023

Purpose

Diabetes is a major public health challenge with widespread prevalence, often leading to complications such as Diabetic Nephropathy (DN)—a chronic condition that progressively impairs kidney function. In this context, it is important to evaluate if Machine learning models can exploit the inherent temporal factor in clinical data to predict the risk of developing DN faster and more accurately than current clinical models.

Methods

Three different databases were used for this literature review: Scopus, Web of Science, and PubMed. Only articles written in English and published between January 2015 and December 2022 were included.

Results

We included 11 studies, from which we discuss a number of algorithms capable of extracting knowledge from clinical data, incorporating dynamic aspects in patient assessment, and exploring their evolution over time. We also present a comparison of the different approaches, their performance, advantages, disadvantages, interpretation, and the value that the time factor can bring to a more successful prediction of diabetic nephropathy.

Conclusion

Our analysis showed that some studies ignored the temporal factor, while others partially exploited it. Greater use of the temporal aspect inherent in Electronic Health Records (EHR) data, together with the integration of omics data, could lead to the development of more reliable and powerful predictive models.
The Effects of Physical Activity Interventions in Children with Autism Spectrum Disorder: a Systematic Review and Network Meta-analysis
Authors: Li Yinhua , Feng Yanqing , Zhong Jiugen , Zou Zhi , Lan Wanting , Shen Yingying , Gong Jiaheng , Zhao Benxuan , Tong Cong , Sit Cindy Hui-Ping , Hou Xiaohui
Published: December 2023

We conducted a network meta-analysis to assess and rank the efficacy of different physical activities on motor function, social function, communication, and stereotyped behavior in children with autism spectrum disorder. PubMed, EBSCO, Cochrane Library, and Web of Science databases were searched through May 25, 2023. A total of 37 studies involving 1200 participants and 17 interventions were included in our study. Based on the ranking probabilities, Tai Chi Chuan and fundamental motor skill intervention were ranked as possibly the most effective intervention for motor function and communication, respectively. Kata techniques had the highest probability of being best for stereotyped behavior and social function. This review provides valuable information that physical activity can be a useful strategy in the management of autism spectrum disorder.
Classification and spectrum optimization method of grease based on infrared spectrum
Authors: Feng Xin , Xia Yanqiu , Xie Peiyuan , Li Xiaohe
Published: December 2023

The infrared (IR) absorption spectral data of 63 kinds of lubricating greases containing six different types of thickeners were obtained using the IR spectroscopy. The Kohonen neural network algorithm was used to identify the type of the lubricating grease. The results show that this machine learning method can effectively eliminate the interference fringes in the IR spectrum, and complete the feature selection and dimensionality reduction of the high-dimensional spectral data. The 63 kinds of greases exhibit spatial clustering under certain IR spectrum recognition spectral bands, which are linked to characteristic peaks of lubricating greases and improve the recognition accuracy of these greases. The model achieved recognition accuracy of 100.00%, 96.08%, 94.87%, 100.00%, and 87.50% for polyurea grease, calcium sulfonate composite grease, aluminum (Al)-based grease, bentonite grease, and lithium-based grease, respectively. Based on the different IR absorption spectrum bands produced by each kind of lubricating grease, the three-dimensional spatial distribution map of the lubricating grease drawn also verifies the accuracy of classification while recognizing the accuracy. This paper demonstrates fast recognition speed and high accuracy, proving that the Kohonen neural network algorithm has an efficient recognition ability for identifying the types of the lubricating grease.
Bewertungskompetenz in Biologieschulbüchern: Eine integrativ-inhaltsanalytische Untersuchung von Schulbuchaufgaben für die Sekundarstufe I
Authors: Leubecher René , Zabel Jörg , Funke Maja , Linnenkemper Victor , Schneider Michael , Bergmann-Gering Alexander
Published: December 2023

Biologielehrkräfte beklagen einen Mangel an Unterrichtsmaterial zur Förderung der Bewertungskompetenz ihrer Schüler:innen. Schulbücher sollten entsprechendes Unterrichtsmaterial, wie bspw. kompetenzorientierte Aufgaben, enthalten, da sie kultusministeriell legitimiert sind und demnach den Bildungsstandards bzw. Lehrplänen folgen sollten. Daher verwundert der beklagte Mangel an Material. Um das Phänomen besser zu verstehen, wurden die Aufgaben (n = 39.464) von in Deutschland zugelassenen Schulbüchern (n = 72) integrativ-inhaltsanalytisch untersucht. Dazu wurden Systematisierungen bioethischer Themenfelder und das Oldenburger Modell der Bewertungskompetenz genutzt und das Ziel verfolgt, zu prüfen, inwieweit die Schulbuchaufgaben den Erwerb von Bewertungskompetenz im Verlauf der Sekundarstufe I ansteuern. Die Ergebnisse zeigen, dass Schulbuchaufgaben zur Förderung von Bewertungskompetenz (n = 3191) insgesamt unterrepräsentiert sind. Ferner werden vor allem sozialethische Themen angesprochen, während wissenschaftsethische Themen kaum aufgegriffen werden. Die vorhandenen Aufgaben zeigen kein systematisches Förderpotential, da sie vor allem auf das Argumentieren abzielen, während die ethische Dimension kaum ausgeleuchtet wird. Auf Grundlage dieser Befunde diskutiert der Beitrag die Qualität von Schulbuchaufgaben zur Förderung von Bewertungskompetenz, die Rolle des Schulbuchs für die Unterrichtsvorbereitung und -durchführung von Biologielehrkräfte sowie als Treiber von curricularen Reformen.
„Fertig, du bist über sieben.“ – Schülervorstellungen zur Kooperation in Experimentierphasen von Naturwissenschaftsunterricht
Authors: Hoffmann Thomas , Menthe Jürgen , Gómez Thews Sina
Published: December 2023

In der Didaktik wird Kooperation in der Regel eher aus der Perspektive der Lernmotive und des sozialen Lernens als aus der des fachlichen Lernens betrachtet. Anhand videographierter Unterrichtssituationen im Naturwissenschaftsunterricht wird im vorliegenden Beitrag rekonstruiert, welche Vorstellungen und Überzeugungen von Schüler*innen (S*S) sich in Interaktionen gemeinsamer Experimentierphasen und in den beobachteten fachbezogenen, gegenständlichen Tätigkeiten niederschlagen. Eine Interaktionsanalyse auf der Grundlage der Dokumentarischen Methode (DM) erfasst die Schülervorstellungen und den durch die Lehrkraft geschaffenen Orientierungsrahmen sowohl auf der Ebene des konjunktiven wie des kommunikativen Wissens. Am Videomaterial werden insgesamt acht z. T. für den Naturwissenschaftsunterricht spezifische Orientierungen der S*S zur Kooperation und zum gemeinsamen Lernen beim Experimentieren rekonstruiert, die sich im Handeln der S*S dokumentieren. Die Ergebnisse werden vor dem Hintergrund der aus fachdidaktisch-normativer Sicht intendierten Lernziele, Kooperationsanlässe und Handlungsabläufe diskutiert. In der Diskussion wird auf methodologischer Ebene der Erkenntnisgewinn durch die Analyse von Schülervorstellungen mittels der DM herausgestellt.
Conceptualizing the Integration of Business and Private Components in Individual Information Systems
Authors: Lanzl Julia , Utz Lena , Afflerbach Patrick , Gimpel Henner
Published: December 2023

Individuals build their individual information system (IIS) with which they manage the boundary between different domains of life. In this age of permanent mobile accessibility, however, the boundary between the private and business domains can become blurred. While some users try to maintain a degree of separation between the two IIS sub-systems (the private and the business information system), others integrate them. Understanding such integration is essential as it affects well-being and performance in both domains. To further this understanding, we introduce a conceptualization of IIS that distinguishes between four layers of IIS: devices, digital identities, relationships, and information. To measure IIS integration, we develop a method based on the IIS components’ usage frequencies in each domain. We evaluate our conceptualization as well as our measurement method by empirically testing a theoretical model of IIS integration on multiple layers. Our data provides empirical support for the importance of relationship integration as one of the four layers. This leads us to the conclusion that even though IIS are composed of four layers, only the relationship layer is of interest regarding IIS integration. Our results are of interest and service to individuals, organizations, and IT designers who aim to manage IIS integration for individual and organizational benefits.
Phosphorus-enriched biochar from biogas residue of Eichhornia crassipes: transformation and release of phosphorus
Authors: Yu Fan , Wang Junxia , Wang Xutong , Wang Yuting , Guo Qianqian , Wang Zhi , Cui Xiaoqiang , Hu Yanjun , Yan Beibei , Chen Guanyi
Published: December 2023

Pyrolysis is an effective technology for treating and utilizing biogas residue. To explore the phosphorus (P) supply capacity of the biochar generated from biogas residue of Eichhornia Crassipes, the P speciation of E. crassipes biogas residue and biomass during pyrolysis (300–700 °C) was analyzed by combining sequential chemical extraction, 31P nuclear magnetic resonance (NMR) and P K-edge X-ray absorption near edge structure (XANES) spectroscopy. Pyrolysis treatment promoted the conversion of amorphous Ca-P phases in biogas residue and biomass into crystalline hydroxyapatite (HAP) phase, which matched the formation of stable HCl-P pools in the biochar derived from biogas residue (AEBs, 22.65–82.04%) and biomass (EBs, 13.08–33.52%) in the process of pyrolysis. Moreover, the total P contents in AEBs (19.43–28.92 mg g−1) were higher than that of EBs (3.41–5.26 mg g−1), indicating that AEBs had a great P reclamation potential. The P release kinetics from AEBs and EBs in water were evaluated via an incubation experiment for 360 h. The P release from both AEBs and EBs conformed to the pseudo-second order kinetics model (R2 > 0.93), but their P release behaviors were different. The P release of AEBs conformed to the diffusion-re-adsorption model, while that of EBs accorded with the diffusion-dissolution model. The diffusive gradients in thin-films (DGT) analysis showed that AEBs could significantly increase soil available P content as compared with EBs. Hence, the biochar produced from biogas residue of E. crassipes via pyrolysis has a good application potential as a P fertilizer.

Graphical Abstract
Deliberation and Ethical Voting Behavior: Evidence from a Campaign Experiment in Benin
Authors: WANTCHEKON LEONARD , GUARDADO JENNY
Published: December 2023

The article provides experimental evidence of the effect of candidate-citizen town-hall meetings on voters’ political behavior. The intervention took place prior to the March 2011 elections in Benin and involved 150 randomly selected villages. In the treatment group, candidates held town-hall meetings where voters deliberated over their electoral platforms. The control group was exposed to the standard campaign—that is, one-way communication of the candidate’s platform by himself or his local broker. We find that town-hall meetings led to a more informed citizenry and higher electoral participation, which diverged little along socioeconomic lines. We also observe a lower effectiveness of vote-buying attempts where town halls took place. This is consistent with town-hall deliberation promoting what we call more “ethical” voters.
Application of Raman spectroscopy to the evaluation of F-actin changes in sea urchin eggs at fertilization
Authors: Mangini Maria , Limatola Nunzia , Ferrara Maria Antonietta , Coppola Giuseppe , Chun Jong Tai , De Luca Anna Chiara , Santella Luigia
Published: December 2023

The actin filaments on the surface of echinoderm oocytes and eggs readily undergo massive reorganization during meiotic maturation and fertilization. In sea urchin eggs, the actin cytoskeletal response to the fertilizing sperm is fast enough to accompany Ca2+ signals and to guide sperm’s entry into the egg. Although recent work using live cell imaging technology confirmed changes in the actin polymerization status in fertilized eggs, as was previously shown using light and electron microscopy, it failed to provide experimental evidence of F-actin depolymerization a few seconds after insemination, which is concurrent with the sperm-induced Ca2+ release. In the present study, we applied Raman microspectroscopy to tackle this issue by examining the spectral profiles of the egg’s subplasmalemmal regions before and after treating the eggs with actin drugs or fertilizing sperm. At both early (15 s) and late (15 min) time points after fertilization, specific peak shifts in the Raman spectra revealed change in the actin structure, and Raman imaging detected the cytoskeletal changes corresponding to the F-actin reorganization visualized with LifeAct-GFP in confocal microscopy. Our observation suggests that the application of Raman spectroscopy, which does not require microinjection of fluorescent probes and exogenous gene expression, may serve as an alternative or even advantageous method in disclosing rapid subtle changes in the subplasmalemmal actin cytoskeleton that are difficult to resolve.
Who is Interested in Participating in Participatory Budgeting?
Authors: Doherty David , Pavel Raluca G. , Jackson Madeline , Garbarski Dana
Published: December 2023

Inequalities in terms of who participates in politics yield policy outcomes that fail to reflect the interests of the broader public. Because these processes fail to engage the full citizenry in political decision-making processes, they are also markers of an anemic civic culture. Advocates of participatory budgeting (PB) – a process implemented at the subnational level in thousands of cities in the United States and beyond that invites residents to participate directly in the process of allocating public resources for local projects – argue that it can alleviate these inequalities. They argue that features of the PB process make it ripe for engaging new participants in the political process and weaving a more inclusive social fabric. We examine the correlates of interest in participating in PB using a survey of Cook County residents. We also consider the extent to which the policy priorities of those who are interested in participating diverge from those who are less interested. Although we find evidence that the process is particularly appealing to younger respondents and those who identify as Latine or Black (as opposed to White), we also find that interest is higher among those with higher socioeconomic status and those who perceive conditions in their neighborhood to already be good. Our evidence also suggests that inequalities in who is interested in participating may not radically affect policy outcomes. However, those who decline to participate cannot reap the broader social and political benefits advocates hope the PB process can foster.
A reflective display based on the electro-microfluidic assembly of particles within suppressed water-in-oil droplet array
Authors: Shen Shitao , Feng Haoqiang , Deng Yueming , Xie Shuting , Yi Zichuan , Jin Mingliang , Zhou Guofu , Mulvaney Paul , Shui Lingling
Published: December 2023

Reflective displays have stimulated considerable interest because of their friendly readability and low energy consumption. Herein, we develop a reflective display technique via an electro-microfluidic assembly of particles (eMAP) strategy whereby colored particles assemble into annular and planar structures inside a dyed water droplet to create “open” and “closed” states of a display pixel. Water-in-oil droplets are compressed within microwells to form a pixel array. The particles dispersed in droplets are driven by deformation-strengthened dielectrophoretic force to achieve fast and reversible motion and assemble into multiple structures. This eMAP based device can display designed information in three primary colors with ≥170° viewing angle, ~0.14 s switching time, and bistability with an optimized material system. This proposed technique demonstrates the basis of a high-performance and energy-saving reflective display, and the display speed and color quality could be further improved by structure and material optimization; exhibiting a potential reflective display technology.
“Puberty age gap”: new method of assessing pubertal timing and its association with mental health problems
Authors: Dehestani Niousha , Vijayakumar Nandita , Ball Gareth , Mansour L Sina , Whittle Sarah , Silk Timothy J.
Published: December 2023

Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing that was built upon multiple pubertal features and their nonlinear changes over time (i.e., with age), and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort (N ~ 9900, aged 9–13 years), we employed three different models to assess pubertal timing. These models aimed to predict chronological age based on: (i) observed physical development, (ii) hormone levels (testosterone and dehydroepiandrosterone [DHEA]), and (iii) a combination of both physical development and hormones. To achieve this, we utilized a supervised machine learning approach, which allowed us to train the models using the available data and make age predictions based on the input pubertal features. The accuracy of these three models was evaluated, and their associations with mental health problems were examined. The new pubertal timing model performed better at capturing age variance compared to the more commonly used linear regression method. Further, the model based on physical features accounted for the most variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility of our new model of pubertal timing and suggests that, relative to hormonal measures, physical measures of pubertal maturation have a stronger association with mental health problems in early adolescence.
Long-term outcome of children with acute promyelocytic leukemia: a randomized study of oral versus intravenous arsenic by SCCLG-APL group
Authors: Huang Dan-Ping , Yang Liang-Chun , Chen Yi-Qiao , Wan Wu-Qing , Zhou Dun-Hua , Mai Hui-Rong , Li Wan-Li , Yang Li-Hua , Lan He-Kui , Chen Hui-Qin , Guo Bi-Yun , Zhen Zi-Jun , Liu Ri-Yang , Chen Guo-Hua , Feng Xiao-Qin , Liang Cong , Wang Li-Na , Li Yu , Luo Jie-Si , Fan Zhong , Luo Xue-Qun , Li Bin , Tang Yan-Lai , Zhang Xiao-Li , Huang Li-Bin
Published: December 2023

Realgar-Indigo naturalis formula (RIF), an oral traditional Chinese medicine mainly containing Realgar (As4S4), is highly effective in treating adult acute promyelocytic leukemia (APL). However, the treatment efficacy and safety of RIF have not been verified in pediatric patients. SCCLG-APL group conducted a multicenter randomized non-inferiority trial to determine whether intravenous arsenic trioxide (ATO) can be substituted by oral RIF in treating pediatric APL. Of 176 eligible patients enrolled, 91 and 85 were randomized to ATO and RIF groups, respectively. Patients were treated with the risk-adapted protocol. Induction, consolidation, and 96-week maintenance treatment contained all-trans-retinoic acid and low-intensity chemotherapy, and either ATO or RIF. The primary endpoint was 5-year event-free survival (EFS). The secondary endpoints were adverse events and hospital days. After a median 6-year follow-up, the 5-year EFS was 97.6% in both groups. However, the RIF group had significantly shorter hospital stays and lower incidence of infection and tended to have less cardiac toxicity. All 4 relapses occurred within 1.5 years after completion of maintenance therapy. No long-term arsenic retentions were observed in either group. Substituting oral RIF for ATO maintains treatment efficacy while reducing hospitalization and adverse events in treating pediatric APL patients, which may be a future treatment strategy for APL.
Deletion of Mettl3 in mesenchymal stem cells promotes acute myeloid leukemia resistance to chemotherapy
Authors: Liao Xinai , Cai Danni , Liu Jingru , Hu Haoran , You Ruolan , Pan Zhipeng , Chen Shucheng , Xu Kaiming , Dai Wei , Zhang Shuxia , Lin Xinjian , Huang Huifang
Published: December 2023

Acute myeloid leukemia (AML) cell survival and chemoresistance are influenced by the existence of bone marrow mesenchymal stem cells (BMMSCs); however, the pathways by which BMMSCs contribute to these processes remain unclear. We earlier revealed that methyltransferase-like 3 (METTL3) expression is significantly reduced in AML BMMSCs and that METTL3 mediates BMMSC adipogenesis to promote chemoresistance in human AML cell lines in vitro. In this investigation, we evaluated the METTL3 function in vivo. Mice exhibiting a conditional removal of Mettl3 in BMMSCs were developed by mating Prrx1-CreERT2;Mettl3fl/+ mice with Mettl3fl/fl mice using the CRISPR-Cas9 system. The Mettl3 deletion increased bone marrow adiposity, enhanced disease progression in the transplantation-induced MLL-AF9 AML mouse model, and chemoresistance to cytarabine. The removal of Mettl3 in BMMSCs resulted in a significant increase in BMMSC adipogenesis. This effect was attributed to the downregulation of AKT1 expression, an AKT serine/threonine kinase 1, in an m6A-dependent manner. The development of chemoresistance in AML is linked to the promoted adipogenesis of BMMSCs. We conclude that METTL3 expression in BMMSCs has a critical function in limiting AML progression and chemoresistance, providing a basis for the progression of therapeutic approaches for AML.
Structural basis of nucleosomal H4K20 recognition and methylation by SUV420H1 methyltransferase
Authors: Lin Folan , Zhang Ruxin , Shao Weihan , Lei Cong , Ma Mingxi , Zhang Ying , Wen Zengqi , Li Wanqiu
Published: December 2023

Histone lysine methyltransferase SUV420H1, which is responsible for site-specific di-/tri-methylation of histone H4 lysine 20 (H4K20), has crucial roles in DNA-templated processes, including DNA replication, DNA damage repair, and chromatin compaction. Its mutations frequently occur in human cancers. Nucleosomes containing the histone variant H2A.Z enhance the catalytic activities of SUV420H1 on H4K20 di-methylation deposition, regulating early replication origins. However, the molecular mechanism by which SUV420H1 specifically recognizes and deposits H4K20 methyl marks on nucleosomes remains poorly understood. Here we report the cryo-electron microscopy structures of SUV420H1 associated with H2A-containing nucleosome core particles (NCPs), and H2A.Z-containing NCPs. We find that SUV420H1 makes extensive site-specific contacts with histone and DNA regions. SUV420H1 C-terminal domain recognizes the H2A–H2B acidic patch of NCPs through its two arginine anchors, thus enabling H4K20 insertion for catalysis specifically. We also identify important residues increasing the catalytic activities of SUV420H1 bound to H2A.Z NCPs. In vitro and in vivo functional analyses reveal that multiple disease-associated mutations at the interfaces are essential for its catalytic activity and chromatin state regulation. Together, our study provides molecular insights into the nucleosome-based recognition and methylation mechanisms of SUV420H1, and a structural basis for understanding SUV420H1-related human disease.
A facile dual-template-directed successive assembly approach to hollow multi-shell mesoporous metal–organic framework particles
Authors: Xu Haidong , Han Ji , Zhao Bin , Sun Ruigang , Zhong Guiyuan , Chen Guangrui , Yamauchi Yusuke , Guan Buyuan
Published: December 2023

Hollow multi-shell mesoporous metal–organic framework (MOF) particles with accessible compartmentalization environments, plentiful heterogeneous interfaces, and abundant framework diversity are expected to hold great potential for catalysis, energy conversion, and biotechnology. However, their synthetic methodology has not yet been established. In this work, a facile dual-template-directed successive assembly approach has been developed for the preparation of monodisperse hollow multi-shell mesoporous MOF (UiO-66-NH2) particles through one-step selective etching of successively grown multi-layer MOFs with alternating two types of mesostructured layers. This strategy enables the preparation of hollow multi-shell mesoporous UiO-66-NH2 nanostructures with controllable shell numbers, accessible mesochannels, large pore volume, tunable shell thickness and chamber sizes. The methodology relies on creating multiple alternating layers of two different mesostructured MOFs via dual-template-directed successive assembly and their difference in framework stability upon chemical etching. Benefiting from the highly accessible Lewis acidic sites and the accumulation of reactants within the multi-compartment architecture, the resultant hollow multi-shell mesoporous UiO-66-NH2 particles exhibit enhanced catalytic activity for CO2 cycloaddition reaction. The dual-template-directed successive assembly strategy paves the way toward the rational construction of elaborate hierarchical MOF nanoarchitectures with specific physical and chemical features for different applications.
An inorganic mineral-based protocell with prebiotic radiation fitness
Authors: Dai Shang , Xie Zhenming , Wang Binqiang , Ye Rui , Ou Xinwen , Wang Chen , Yu Ning , Huang Cheng , Zhao Jie , Cai Chunhui , Zhang Furong , Buratto Damiano , Khan Taimoor , Qiao Yan , Hua Yuejin , Zhou Ruhong , Tian Bing
Published: December 2023

Protocell fitness under extreme prebiotic conditions is critical in understanding the origin of life. However, little is known about protocell’s survival and fitness under prebiotic radiations. Here we present a radioresistant protocell model based on assembly of two types of coacervate droplets, which are formed through interactions of inorganic polyphosphate (polyP) with divalent metal cation and cationic tripeptide, respectively. Among the coacervate droplets, only the polyP-Mn droplet is radiotolerant and provides strong protection for recruited proteins. The radiosensitive polyP-tripeptide droplet sequestered with both proteins and DNA could be encapsulated inside the polyP-Mn droplet, and form into a compartmentalized protocell. The protocell protects the inner nucleoid-like condensate through efficient reactive oxygen species’ scavenging capacity of intracellular nonenzymic antioxidants including Mn-phosphate and Mn-peptide. Our results demonstrate a radioresistant protocell model with redox reaction system in response to ionizing radiation, which might enable the protocell fitness to prebiotic radiation on the primitive Earth preceding the emergence of enzyme-based fitness. This protocell might also provide applications in synthetic biology as bioreactor or drug delivery system.
Harmonizing sound and light: X-ray imaging unveils acoustic signatures of stochastic inter-regime instabilities during laser melting
Authors: Hamidi Nasab Milad , Masinelli Giulio , de Formanoir Charlotte , Schlenger Lucas , Van Petegem Steven , Esmaeilzadeh Reza , Wasmer Kilian , Ganvir Ashish , Salminen Antti , Aymanns Florian , Marone Federica , Pandiyan Vigneashwara , Goel Sneha , Logé Roland E.
Published: December 2023

Laser powder bed fusion (LPBF) is a metal additive manufacturing technique involving complex interplays between vapor, liquid, and solid phases. Despite LPBF’s advantageous capabilities compared to conventional manufacturing methods, the underlying physical phenomena can result in inter-regime instabilities followed by transitions between conduction and keyhole melting regimes — leading to defects. We investigate these issues through operando synchrotron X-ray imaging synchronized with acoustic emission recording, during the remelting processes of LPBF-produced thin walls, monitoring regime changes occurring under constant laser processing parameters. The collected data show an increment in acoustic signal amplitude when switching from conduction to keyhole regime, which we correlate to changes in laser absorptivity. Moreover, a full correlation between X-ray imaging and the acoustic signals permits the design of a simple filtering algorithm to predict the melting regimes. As a result, conduction, stable keyhole, and unstable keyhole regimes are identified with a time resolution of 100 µs, even under rapid transitions, providing a straightforward method to accurately detect undesired processing regimes without the use of artificial intelligence.
A monoacylglycerol lipase inhibitor showing therapeutic efficacy in mice without central side effects or dependence
Authors: Jiang Ming , Huizenga Mirjam C. W. , Wirt Jonah L. , Paloczi Janos , Amedi Avand , van den Berg Richard J. B. H. N. , Benz Joerg , Collin Ludovic , Deng Hui , Di Xinyu , Driever Wouter F. , Florea Bogdan I. , Grether Uwe , Janssen Antonius P. A. , Hankemeier Thomas , Heitman Laura H. , Lam Tsang-Wai , Mohr Florian , Pavlovic Anto , Ruf Iris , van den Hurk Helma , Stevens Anna F. , van der Vliet Daan , van der Wel Tom , Wittwer Matthias B. , van Boeckel Constant A. A. , Pacher Pal , Hohmann Andrea G. , van der Stelt Mario
Published: December 2023

Monoacylglycerol lipase (MAGL) regulates endocannabinoid 2-arachidonoylglycerol (2-AG) and eicosanoid signalling. MAGL inhibition provides therapeutic opportunities but clinical potential is limited by central nervous system (CNS)-mediated side effects. Here, we report the discovery of LEI-515, a peripherally restricted, reversible MAGL inhibitor, using high throughput screening and a medicinal chemistry programme. LEI-515 increased 2-AG levels in peripheral organs, but not mouse brain. LEI-515 attenuated liver necrosis, oxidative stress and inflammation in a CCl4-induced acute liver injury model. LEI-515 suppressed chemotherapy-induced neuropathic nociception in mice without inducing cardinal signs of CB1 activation. Antinociceptive efficacy of LEI-515 was blocked by CB2, but not CB1, antagonists. The CB1 antagonist rimonabant precipitated signs of physical dependence in mice treated chronically with a global MAGL inhibitor (JZL184), and an orthosteric cannabinoid agonist (WIN55,212-2), but not with LEI-515. Our data support targeting peripheral MAGL as a promising therapeutic strategy for developing safe and effective anti-inflammatory and analgesic agents.
Neural substrates of parallel devaluation-sensitive and devaluation-insensitive Pavlovian learning in humans
Authors: Pool Eva R. , Pauli Wolfgang M. , Cross Logan , O’Doherty John P.
Published: December 2023

We aim to differentiate the brain regions involved in the learning and encoding of Pavlovian associations sensitive to changes in outcome value from those that are not sensitive to such changes by combining a learning task with outcome devaluation, eye-tracking, and functional magnetic resonance imaging in humans. Contrary to theoretical expectation, voxels correlating with reward prediction errors in the ventral striatum and subgenual cingulate appear to be sensitive to devaluation. Moreover, regions encoding state prediction errors appear to be devaluation insensitive. We can also distinguish regions encoding predictions about outcome taste identity from predictions about expected spatial location. Regions encoding predictions about taste identity seem devaluation sensitive while those encoding predictions about an outcome’s spatial location seem devaluation insensitive. These findings suggest the existence of multiple and distinct associative mechanisms in the brain and help identify putative neural correlates for the parallel expression of both devaluation sensitive and insensitive conditioned behaviors.
Electrosynthesis of buckyballs with fused-ring systems from PCBM and its analogue
Authors: Wang Wei-Feng , Liu Kai-Qing , Niu Chuang , Wang Yun-Shu , Yao Yang-Rong , Yin Zheng-Chun , Chen Muqing , Ye Shi-Qi , Yang Shangfeng , Wang Guan-Wu
Published: December 2023

[6,6]-Phenyl-C61-butyric acid methyl ester (PCBM), a star molecule in the fullerene field, has found wide applications in materials science. Herein, electrosynthesis of buckyballs with fused-ring systems has been achieved through radical α-C−H functionalization of the side-chain ester for both PCBM and its analogue, [6,6]-phenyl-C61-propionic acid methyl ester (PCPM), in the presence of a trace amount of oxygen. Two classes of buckyballs with fused bi- and tricyclic carbocycles have been electrochemically synthesized. Furthermore, an unknown type of a bisfulleroid with two tethered [6,6]-open orifices can also be efficiently generated from PCPM. All three types of products have been confirmed by single-crystal X-ray crystallography. A representative intramolecularly annulated isomer of PCBM has been applied as an additive to inverted planar perovskite solar cells and boosted a significant enhancement of power conversion efficiency from 15.83% to 17.67%.
Environmental modulation of global epistasis in a drug resistance fitness landscape
Authors: Diaz-Colunga Juan , Sanchez Alvaro , Ogbunugafor C. Brandon
Published: December 2023

Interactions between mutations (epistasis) can add substantial complexity to genotype-phenotype maps, hampering our ability to predict evolution. Yet, recent studies have shown that the fitness effect of a mutation can often be predicted from the fitness of its genetic background using simple, linear relationships. This phenomenon, termed global epistasis, has been leveraged to reconstruct fitness landscapes and infer adaptive trajectories in a wide variety of contexts. However, little attention has been paid to how patterns of global epistasis may be affected by environmental variation, despite this variation frequently being a major driver of evolution. This is particularly relevant for the evolution of drug resistance, where antimicrobial drugs may change the environment faced by pathogens and shape their adaptive trajectories in ways that can be difficult to predict. By analyzing a fitness landscape of four mutations in a gene encoding an essential enzyme of P. falciparum (a parasite cause of malaria), here we show that patterns of global epistasis can be strongly modulated by the concentration of a drug in the environment. Expanding on previous theoretical results, we demonstrate that this modulation can be quantitatively explained by how specific gene-by-gene interactions are modified by drug dose. Importantly, our results highlight the need to incorporate potential environmental variation into the global epistasis framework in order to predict adaptation in dynamic environments.
Expansion microscopy applied to mono- and dual-species biofilms
Authors: Valdivieso González David , Jara Josué , Almendro-Vedia Víctor G. , Orgaz Belén , López-Montero Iván
Published: December 2023

Expansion microscopy (ExM) is a new super-resolution technique based on embedding the biological sample within a hydrogel and its physical expansion after swelling. This allows increasing its size by several times while preserving its structural details. Applied to prokaryotic cells, ExM requires digestion steps for efficient expansion as bacteria are surrounded by a rigid cell wall. Furthermore, bacteria can live in social groups forming biofilms, where cells are protected from environmental stresses by a self-produced matrix. The extracellular matrix represents an additional impenetrable barrier for ExM. Here we optimize the current protocols of ExM and apply them to mono- and dual-species biofilms formed by clinical isolates of Limosilactobacillus reuteri, Enterococcus faecalis, Serratia marcescens and Staphylococcus aureus. Using scanning electron microscopy for comparison, our results demonstrate that embedded bacteria expanded 3-fold. Moreover, ExM allowed visualizing the three-dimensional architecture of the biofilm and identifying the distribution of different microbial species and their interactions. We also detected the presence of the extracellular matrix after expansion with a specific stain of the polysaccharide component. The potential applications of ExM in biofilms will improve our understanding of these complex communities and have far-reaching implications for industrial and clinical research.
Real-time estimation of the effective reproduction number of COVID-19 from behavioral data
Authors: Bokányi Eszter , Vizi Zsolt , Koltai Júlia , Röst Gergely , Karsai Márton
Published: December 2023

Monitoring the effective reproduction number$$R_t$$Rtof a rapidly unfolding pandemic in real-time is key to successful mitigation and prevention strategies. However, existing methods based on case numbers, hospital admissions or fatalities suffer from multiple measurement biases and temporal lags due to high test positivity rates or delays in symptom development or administrative reporting. Alternative methods such as web search and social media tracking are less directly indicating epidemic prevalence over time. We instead record age-stratified anonymous contact matrices at a daily resolution using a longitudinal online-offline survey in Hungary during the first two waves of the COVID-19 pandemic. This approach is innovative, cheap, and provides information in near real-time for estimating$$R_t$$Rtat a daily resolution. Moreover, it allows to complement traditional surveillance systems by signaling periods when official monitoring infrastructures are unreliable due to observational biases.
A graph-based approach can improve keypoint detection of complex poses: a proof-of-concept on injury occurrences in alpine ski racing
Authors: Zwölfer Michael , Heinrich Dieter , Wandt Bastian , Rhodin Helge , Spörri Jörg , Nachbauer Werner
Published: December 2023

For most applications, 2D keypoint detection works well and offers a simple and fast tool to analyse human movements. However, there remain many situations where even the best state-of-the-art algorithms reach their limits and fail to detect human keypoints correctly. Such situations may occur especially when individual body parts are occluded, twisted, or when the whole person is flipped. Especially when analysing injuries in alpine ski racing, such twisted and rotated body positions occur frequently. To improve the detection of keypoints for this application, we developed a novel method that refines keypoint estimates by rotating the input videos. We select the best rotation for every frame with a graph-based global solver. Thereby, we improve keypoint detection of an arbitrary pose estimation algorithm, in particular for ‘hard’ keypoints. In the current proof-of-concept study, we show that our approach outperforms standard keypoint detection results in all categories and in all metrics, in injury-related out-of-balance and fall situations by a large margin as well as previous methods, in performance and robustness. The Injury Ski II dataset was made publicly available, aiming to facilitate the investigation of sports accidents based on computer vision in the future.
Quantum mechanisms for selective detection in complex gas mixtures using conductive sensors
Authors: Kamarchuk G. , Pospelov A. , Kamarchuk L. , Belan V. , Herus A. , Savytskyi A. , Vakula V. , Harbuz D. , Gudimenko V. , Faulques E.
Published: December 2023

In this paper, we consider new quantum mechanisms for selective detection in complex gaseous media which provide the highest possible efficiency of quantum sensors and for the first time analyze their nature. On the basis of these quantum mechanisms, the concepts of quantum detection and innovative methods of analysis are developed, which are virtually impossible to implement in the conventional conductive sensors and nanosensors. Examples of original solutions to problems in the field of detection and analysis of human breath using point-contact sensors are considered. A new method of analysis based on detection of metastable quantum states of the "point-contact sensor—breath" system in dynamic mode is proposed. The conductance histogram of dendritic Yanson point contacts recorded for this system is a unique energy signature of breath which allows differentiation between the states of human body. We demonstrate that nanosized Yanson point contacts, which, thanks to their quantum properties, can replace a massive spectrometer, open up wide opportunities for solving complex problems in the field of breath analysis using a new generation of portable high-tech quantum sensor devices.
Develop the artificial neural network approach to predict thermal transport analysis of nanofluid inside a porous enclosure
Authors: Nasir Saleem , Berrouk Abdallah S. , Gul Taza , Ali Aatif
Published: December 2023

This study explores the impacts of heat transportation on hybrid (Ag + MgO) nanofluid flow in a porous cavity using artificial neural networks (Bayesian regularization approach (BRT-ANN) neural networks technique). The cavity considered in this analysis is a semicircular shape with a heated and a cooled wall. The dynamics of flow and energy transmission in the cavity are influenced by various features such as the effect of magnetize field, porosity and volume fraction of nanoparticles. To explore the outcomes of these features on hybrid nanofluid thermal and flow transport, a BRT-ANN model is developed. The ANN model is trained using a dataset generated through numerical scheme. The trained ANN model is then used to predict the heat and flow transport characteristics for various input parameters. The accuracy of the ANN simulation is confirmed through comparison of the predicted results with the results obtained through numerical simulations. By maintaining the corrugated wall uniformly heated, we inspected the levels of isotherms, streamlines and heat transfer distribution. A graphical illustration highlights the characteristics of the Hartmann and Rayleigh numbers, permeability component in porous material, drag force and rate of energy transport. According to the percentage analysis, nanofluids (Ag + MgO/H2O) are prominent to enhance the thermal distribution of traditional fluids. The study demonstrates the potential of ANNs in predicting the impacts of various factors on hybrid nanofluid flow and heat transport, which can be useful in designing and optimizing heat transfer systems.