bluuebunny/crossref_metadata_2025 huggingface dataset:
An improved fruit fly optimization algorithm with Q-learning for solving distributed permutation flow shop scheduling problems
Authors: Zhao Cai , Wu Lianghong , Zuo Cili , Zhang Hongqiang
Published: May 2024

The distributed permutation flow shop scheduling problem (DPFSP) is one of the hottest issues in the context of economic globalization. In this paper, a Q-learning enhanced fruit fly optimization algorithm (QFOA) is proposed to solve the DPFSP with the goal of minimizing the makespan. First, a hybrid strategy is used to cooperatively initialize the position of the fruit fly in the solution space and the boundary properties are used to improve the operation efficiency of QFOA. Second, the neighborhood structure based on problem knowledge is designed in the smell stage to generate neighborhood solutions, and the Q-learning method is conducive to the selection of high-quality neighborhood structures. Moreover, a local search algorithm based on key factories is designed to improve the solution accuracy by processing sequences of subjobs from key factories. Finally, the proposed QFOA is compared with the state-of-the-art algorithms for solving 720 well-known large-scale benchmark instances. The experimental results demonstrate the most outstanding performance of QFOA.
Novel titanium-based sulfur-containing BMG for PBF-LB/M
Authors: Schönrath Hanna , Wegner Jan , Frey Maximilian , Schroer Martin A. , Jin Xueze , Pérez-Prado María Teresa , Busch Ralf , Kleszczynski Stefan
Published: May 2024

This paper investigates the additive manufacturing route for a novel glass-forming titanium-based sulfur-containing alloy of the composition $${\text{Ti}}_{60} {\text{Zr}}_{15} {\text{Cu}}_{17} {\text{S}}_{8}$$

Ti
60

Zr
15

Cu
17

S
8

. This system is a promising candidate for medical devices since the lack of toxic components is combined with a high corrosion resistance and strength. Preliminary experiments and simulations show a general processability of bulk material by powder bed fusion technologies. TEM and XRD reveal an amorphous microstructure of laser-treated surfaces. Ultrasonic atomization is used to fabricate a flowable powder feed stock with spherical morphology and crystalline microstructure, which is suitable for processing in powder bed fusion. Correlations between detected crystalline phase formations and melt pool dynamics are revealed by SEM and EDX. It is shown that bulk samples with a high relative density and partially crystalline microstructure can be manufactured.
Quantification and valorization of compost derived from urban households’ waste in Bukavu City, Eastern D.R. Congo
Authors: Chuma Géant B. , Mondo Jean M. , Ndeko Adrien B. , Akuzibwe Etienne M. , Bagula Espoir M. , Mushagalusa Gustave N.
Published: May 2024

This study focused on quantifying and valorizing domestic waste in Bukavu, a rapidly growing city in eastern Democratic Republic of Congo (DRC). With increasing anthropogenic pressure, waste management has become a pressing issue, yet documentation in this area is still limited. This study aimed to fill this gap by providing comprehensive data on domestic waste generation, composition, and disposal practices in Bukavu city. Through field surveys and analysis, waste quantities and types were documented, revealing significant challenges in waste management infrastructure and practices. Additionally, the study explores opportunities for waste valorization, particularly through composting, given the region's agricultural potential and growing urban food demand. The findings revealed that ~ 5% of the domestic waste is biodegradable, with the majority consisting of metals and plastics. These wastes are predominantly used as livestock feed (10%), incinerated (66%), or buried (17%), with ~ 5% undergoing composting. Waste management is primarily handled by children (82%), with very few non-governmental organizations (NGOs) involved in such activities. Among the three composting methods evaluated, outputs from vermicomposting demonstrated superior qualities in terms of promoting crop growth, increasing yield, and achieving a high germination index. Overall, the application of composts improved plant growth and yield parameters of the two major legumes (common bean and soybean). Future interventions should explore the implementation of large-scale composting units at the household or citywide level, while also considering additional strategies to enhance the quality of the compost products. Such efforts are crucial in mitigating the environmental and health impacts of urban household waste and promoting sustainable practices in urban agriculture.
How News Coverage of Misinformation Shapes Perceptions and Trust
Authors: Thorson Emily
Published: May 2024

This manuscript takes on two related questions: how do the media cover this important issue, and how does exposure to this coverage affect public perceptions, including trust? A content analysis shows that most media coverage explicitly blames social media for the problem, and two experiments find that while exposure to news coverage of misinformation makes people less trusting of news on social media, it increases trust in print news. This counter-intuitive effect occurs because exposure to news about misinformation increases the perceived value of traditional journalistic norms. Finally, exposure to misinformation coverage has no measurable effect political trust or internal efficacy, and political interest is a strong predictor of interest in news coverage of misinformation across partisan lines. These results suggest that many Americans see legacy media as bulwark against changes that threaten to distort the information environment.
Feminist Philosophy of Science
Authors: Bueter Anke
Published: May 2024

Feminist scholars have identified pervasive gender discrimination in science as an institution, as well as gender bias in the very content of many scientific theories. An ameliorative project at heart, feminist philosophy of science has inquired into the social and epistemological roots and consequences of these problems and into their potential solutions. Most feminist philosophers agree on a need for diversity in scientific communities to counter the detrimental effects of gender bias. Diversity could thus serve as a unifying concept for a potential consensus of the field. Yet there are substantial differences in the kinds and roles of diversity envisaged. This element argues that we need diversity, both in terms of social locations and of values, to overcome former biases and blind spots. Diversity as such, however, is insufficient. To reap its epistemic benefits, diversity also needs to be institutionalised in a way that counters various forms of epistemic injustice.
Between Appeasement and Accommodation: Kōmeitō's Policy Influence under Second Abe Administration
Authors: Sohn Sukeui
Published: May 2024

This study examines the Kōmeitō's strategies for policy influence within the coalition framework with its coalition partner, the Liberal Democratic Party (LDP) during the period of Second Abe Administration (2012–2020). As a junior coalition partner, Kōmeitō faces unity–distinctiveness dilemma, where it must accommodate policy demands of the senior partner while appeasing its core support base, Sōka Gakkai. This article argues that the junior partner's strategies for policy influence are determined by two factors: overlap/distinctiveness of policy inclinations and the positive/negative issue associations measured by the level of involvement in decision-making, i.e. portfolio allocation. Three cases are analyzed to elucidate the diversity of Kōmeitō's policy influence, the strategies of which range from corrective moderation, to nudging, to threats, all utilized to maintain a balance between reinforcing “distinctiveness” from the senior partner and consolidating coalition coherence to sustain competence within the coalition framework.
GREENER IS CHEAPER: AN EXAMPLE FROM OFFSHORE WIND FARMS
Authors: Bhattacharya Subhamoy , Kammen Dan
Published: May 2024

Offshore wind farms (OWF) are now in operation and increasingly under construction as scalable, sustainable energy sources. In fact OWFs are currently the cheapest form of new energy projects in Europe. The levelized cost of energy (LCOE) for OWF has fallen drastically due to decades of innovation facilitated by both taxpayer and private sector funding. This emerging industry is experiencing massive worldwide growth with the potential to accelerate the decarbonization of regional and the global economy as well as bring a reliable source of green hydrogen into commercial use, all with minimal disruption to ecosystems and impacts on biodiversity. This paper provides a historical perspective of wind energy harnessing and shows that wind turbines are the oldest, largest and one of the smartest machines. We also highlight the potential of offshore wind energy to provide new solutions to (a) meet clean energy demand for a growing world population, (b) improve energy security of nations through other downstream technologies such as production and storage of dispatchable fuel (such as green hydrogen battery storage) and (c) through supply complementarity improve resilience of nuclear power plants in high-seismic-activity areas. Offshore wind industry can also become a gold standard for future industries, and the paper provides insights into the new green economics and jobs and factories for the future. We show that environment-friendly regulation is driving innovations even further to enhance sustainability of OWF. Examples include material recycling, landfill ban on blade disposal and ecofriendly low-noise offshore construction to protect biodiversity.
A classification of automorphic Lie algebras on complex tori
Authors: Knibbeler Vincent , Lombardo Sara , Oelen Casper
Published: May 2024

We classify the automorphic Lie algebras of equivariant maps from a complex torus to $\mathfrak{sl}_2(\mathbb{C})$. For each case, we compute a basis in a normal form. The automorphic Lie algebras correspond precisely to two disjoint families of Lie algebras parametrised by the modular curve of $\mathrm{PSL}_2({\mathbb{Z}})$, apart from four cases, which are all isomorphic to Onsager’s algebra.
The Thermal Evolution of Western Norway Based on Multi‐Sample Models of an Elevation Transect: Implications for the Formation of High‐Elevation Low‐Relief Surfaces on an Elevated Rifted Continental Margin
Authors: Hestnes Å. , Gasser D. , Ketcham R. , Dunkl I. , Ksienzyk A. K. , Scheiber T. , Sirevaag H. , Jacobs J.
Published: May 2024

The post‐Caledonian thermal and geomorphological evolution of onshore Western Norway is poorly understood, including the formation and age of the high‐elevation low‐relief surfaces seen across the Norwegian landscape. We present new apatite fission track (AFT) and (U‐Th‐Sm)/He analyses from an elevation transect (ET) covering ∼1,800 m vertical distance below a high‐elevation low‐relief surface in the inner Nordfjord. The AFT ages increase with elevation from 159 ± 11 Ma to 256 ± 21 Ma and apatite (U‐Th‐Sm)/He ages increase with elevation from 80 ± 4 Ma to 277 ± 15 Ma. In order to test different possible thermal evolutions, we present the first multi‐sample thermal history models from Norway using HeFTy combining both AFT and (U‐Th‐Sm)/He ages along the ET, refining available thermal history models for the area considerably. The best modeling results are found for a thermal evolution with slow cooling throughout the Mesozoic and increased cooling rates from the Late Cretaceous until present, indicating a Cenozoic age for the low‐relief surface at the top of the transect. The models also allow for cooling to surface conditions in the Late Jurassic, but such an evolution must have been followed by rapid burial by 1.5–3 km Cretaceous sediments, and by re‐exhumation in the Cenozoic, indicating that the low‐relief surface cannot represent a simply uplifted Jurassic or Cretaceous peneplain. We compare our results with multi‐sample models from the wider North Atlantic region, supporting previous findings of Cenozoic exhumation and landscape forming processes within that region.
ZDR Backwards Arc: Evidence of Multi‐Directional Size Sorting in the Storm Producing 201.9 mm Hourly Rainfall
Authors: Li Haoran , Yin Jinfang , Kumjian Matthew
Published: May 2024

In this study, we present radar polarimetric characterizations of the storm producing 201.9 mm hourly rainfall on 20 July 2021 in Zhengzhou, China. We employed the separation signatures of enhanced polarimetric observations to investigate hydrometeor size sorting processes, and developed an algorithm to quantify the size sorting directions. Analysis of coupled polarimetric observations unraveled multi‐directional size sorting (MSS) occurred as a low‐level differential reflectivity ZDR backwards arc signature encompassing the rainfall center during the most intensive rainfall period. The rainfall intensification is in step with the increase of size sorting directions. Model simulations with two‐moment microphysics scheme suggest that the presence of arc‐shaped updrafts is conducive to MSS and increased rain rates around the rainfall center. This work sheds novel insights into the kinematics‐driven microphysics in extreme rainfall storms, warranting the potential of using coupled polarimetric signatures for warning catastrophic extreme rainfall events.
Decreased frontal theta frequency during the presence of smartphone among children: an EEG study
Authors: Shaer Rawnaq , Eldin Sheherban Nasser , Gashri Carmel , Horowitz-Kraus Tzipi
Published: May 2024

Background

Smart devices have become an integral part of our lives. However, research has highlighted the potential implications of smartphone presence on task performance, particularly in young children. This study aimed to determine the effect of a smartphone presence on brainwaves associated with cognitive interruption in children.

Methods

EEG data were collected from 5.3 to 8.5-year-old children performing a simple reaction time task with and without the presence of a smartphone. Theta and alpha bands were calculated, and repeated measure analysis of variance was performed to assess the impact of two conditions on alpha and theta bands: 1) with the presence and; 2) without the presence of a smartphone. EEG waveforms were also correlated with standardized cognitive measures evaluating attention abilities using Pearson correlation.

Results

Theta and alpha activity values were higher in the absence vs the presence of a smartphone, with a significant difference between theta bands for the two study conditions. Moreover, the difference between theta bands in the two conditions was significantly correlated with lower scores on an auditory attention test.

Conclusions

The existence of an interactive electronic device during cognitive tasks is associated with alterations in brain activity related to cognitive control.

Impact

The presence of a smartphone during a simple reaction time task in young children was associated with a significant decrease in frontal theta frequency.

A trend of a decreased alpha band in the presence of a smartphone.

The differences in theta and alpha frequencies between conditions were significantly correlated with lower scores in auditory and visual attention and inhibition tests.
A novel TGFbeta/TGILR axis mediates crosstalk between cancer-associated fibroblasts and tumor cells to drive gastric cancer progression
Authors: Qin Shanshan , Guo Qiwei , Liu Yue , Zhang Xiangang , Huang Pan , Yu Hedong , Xia Lingyun , Leng Weidong , Li Dandan
Published: May 2024

Transforming growth factor beta (TGFβ) signaling plays a critical role in tumorigenesis and metastasis. However, little is known about the biological function of TGFbeta-induced lncRNA in cancer. In this study, we discovered a novel TGFbeta-induced lncRNA, termed TGILR, whose function in cancer remains unknown to date. TGILR expression was directly activated by the canonical TGFbeta/SMAD3 signaling axis, and this activation is highly conserved in cancer. Clinical analysis showed that TGILR overexpression showed a significant correlation with lymph node metastasis and poor survival and was an independent prognostic factor in gastric cancer (GC). Depletion of TGILR caused an obvious inhibitory effect on GC cell proliferation, invasion, and epithelial-mesenchymal transition (EMT) in vitro and in vivo. More importantly, we demonstrated that TGFbeta signaling in GC was overactivated due to cancer-associated fibroblast (CAF) infiltration. Mechanistically, increased level of CAF-secreted TGFbeta activates TGFbeta signaling, leading to TGILR overexpression in GC cells. Meanwhile, TGILR overexpression inhibited the microRNA biogenesis of miR-1306 and miR-33a by interacting with TARBP2 and reducing its protein stability, thereby promoting GC progression via TCF4-mediated EMT signaling. In conclusion, CAF infiltration drives GC metastasis and EMT signaling through activating TGFbeta/TGILR axis. Targeted blocking of CAF-derived TGFbeta should be a promising anticancer strategy in GC.
Tumor microenvironment-induced FOXM1 regulates ovarian cancer stemness
Authors: Battistini Chiara , Kenny Hilary A. , Zambuto Melissa , Nieddu Valentina , Melocchi Valentina , Decio Alessandra , Lo Riso Pietro , Villa Carlo Emanuele , Gatto Alessia , Ghioni Mariacristina , Porta Francesca M. , Testa Giuseppe , Giavazzi Raffaella , Colombo Nicoletta , Bianchi Fabrizio , Lengyel Ernst , Cavallaro Ugo
Published: May 2024

In ovarian tumors, the omental microenvironment profoundly influences the behavior of cancer cells and sustains the acquisition of stem-like traits, with major impacts on tumor aggressiveness and relapse. Here, we leverage a patient-derived platform of organotypic cultures to study the crosstalk between the tumor microenvironment and ovarian cancer stem cells. We discovered that the pro-tumorigenic transcription factor FOXM1 is specifically induced by the microenvironment in ovarian cancer stem cells, through activation of FAK/YAP signaling. The microenvironment-induced FOXM1 sustains stemness, and its inactivation reduces cancer stem cells survival in the omental niche and enhances their response to the PARP inhibitor Olaparib. By unveiling the novel role of FOXM1 in ovarian cancer stemness, our findings highlight patient-derived organotypic co-cultures as a powerful tool to capture clinically relevant mechanisms of the microenvironment/cancer stem cells crosstalk, contributing to the identification of tumor vulnerabilities.
IFRD1 promotes tumor cells “low-cost” survival under glutamine starvation via inhibiting histone H1.0 nucleophagy
Authors: Huang Yabin , Meng Fanzheng , Zeng Taofei , Thorne Rick Francis , He Lifang , Zha Qingrui , Li Hairui , Liu Hong , Lang Chuandong , Xiong Wanxiang , Pan Shixiang , Yin Dalong , Wu Mian , Sun Xuedan , Liu Lianxin
Published: May 2024

Glutamine addiction represents a metabolic vulnerability of cancer cells; however, effective therapeutic targeting of the pathways involved remains to be realized. Here, we disclose the critical role of interferon-related developmental regulator 1 (IFRD1) in the adaptive survival of hepatocellular carcinoma (HCC) cells during glutamine starvation. IFRD1 is induced under glutamine starvation to inhibit autophagy by promoting the proteasomal degradation of the key autophagy regulator ATG14 in a TRIM21-dependent manner. Conversely, targeting IFRD1 in the glutamine-deprived state increases autophagy flux, triggering cancer cell exhaustive death. This effect largely results from the nucleophilic degradation of histone H1.0 and the ensuing unchecked increases in ribosome and protein biosynthesis associated with globally enhanced chromatin accessibility. Intriguingly, IFRD1 depletion in preclinical HCC models synergizes with the treatment of the glutaminase-1 selective inhibitor CB-839 to potentiate the effect of limiting glutamine. Together, our findings reveal how IFRD1 supports the adaptive survival of cancer cells under glutamine starvation, further highlighting the potential of IFRD1 as a therapeutic target in anti-cancer applications.
An isoform quantitative trait locus in SBNO2 links genetic susceptibility to Crohn’s disease with defective antimicrobial activity
Authors: Aschenbrenner Dominik , Nassiri Isar , Venkateswaran Suresh , Pandey Sumeet , Page Matthew , Drowley Lauren , Armstrong Martin , Kugathasan Subra , Fairfax Benjamin , Uhlig Holm H.
Published: May 2024

Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn’s disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn’s disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn’s disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.
L-RNA aptamer-based CXCL12 inhibition combined with radiotherapy in newly-diagnosed glioblastoma: dose escalation of the phase I/II GLORIA trial
Authors: Giordano Frank A. , Layer Julian P. , Leonardelli Sonia , Friker Lea L. , Turiello Roberta , Corvino Dillon , Zeyen Thomas , Schaub Christina , Müller Wolf , Sperk Elena , Schmeel Leonard Christopher , Sahm Katharina , Oster Christoph , Kebir Sied , Hambsch Peter , Pietsch Torsten , Bisdas Sotirios , Platten Michael , Glas Martin , Seidel Clemens , Herrlinger Ulrich , Hölzel Michael
Published: May 2024

The chemokine CXCL12 promotes glioblastoma (GBM) recurrence after radiotherapy (RT) by facilitating vasculogenesis. Here we report outcomes of the dose-escalation part of GLORIA (NCT04121455), a phase I/II trial combining RT and the CXCL12-neutralizing aptamer olaptesed pegol (NOX-A12; 200/400/600 mg per week) in patients with incompletely resected, newly-diagnosed GBM lacking MGMT methylation. The primary endpoint was safety, secondary endpoints included maximum tolerable dose (MTD), recommended phase II dose (RP2D), NOX-A12 plasma levels, topography of recurrence, tumor vascularization, neurologic assessment in neuro-oncology (NANO), quality of life (QOL), median progression-free survival (PFS), 6-months PFS and overall survival (OS). Treatment was safe with no dose-limiting toxicities or treatment-related deaths. The MTD has not been reached and, thus, 600 mg per week of NOX-A12 was established as RP2D for the ongoing expansion part of the trial. With increasing NOX-A12 dose levels, a corresponding increase of NOX-A12 plasma levels was observed. Of ten patients enrolled, nine showed radiographic responses, four reached partial remission. All but one patient (90%) showed at best response reduced perfusion values in terms of relative cerebral blood volume (rCBV). The median PFS was 174 (range 58-260) days, 6-month PFS was 40.0% and the median OS 389 (144-562) days. In a post-hoc exploratory analysis of tumor tissue, higher frequency of CXCL12+ endothelial and glioma cells was significantly associated with longer PFS under NOX-A12. Our data imply safety of NOX-A12 and its efficacy signal warrants further investigation.
On the quality of commercial chemical vapour deposited hexagonal boron nitride
Authors: Yuan Yue , Weber Jonas , Li Junzhu , Tian Bo , Ma Yinchang , Zhang Xixiang , Taniguchi Takashi , Watanabe Kenji , Lanza Mario
Published: May 2024

The semiconductors industry has put its eyes on two-dimensional (2D) materials produced by chemical vapour deposition (CVD) because they can be grown at the wafer level with small thickness fluctuations, which is necessary to build electronic devices and circuits. However, CVD-grown 2D materials can contain significant amounts of lattice distortions, which degrades the performance at the device level and increases device-to-device variability. Here we statistically analyse the quality of commercially available CVD-grown hexagonal boron nitride (h-BN) from the most popular suppliers. h-BN is of strategic importance because it is one of the few insulating 2D materials, and can be used as anti-scattering substrate and gate dielectric. We find that the leakage current and electrical homogeneity of all commercially available CVD h-BN samples are significantly worse than those of mechanically exfoliated h-BN of similar thickness. Moreover, in most cases the properties of the CVD h-BN samples analysed don’t match the technical specifications given by the suppliers, and the sample-to-sample variability is unsuitable for the reproducible fabrication of capacitors, transistors or memristors in different batches. In the short term, suppliers should try to provide accurate sample specifications matching the properties of the commercialized materials, and researchers should keep such inaccuracies in mind; and in the middle term suppliers should try to reduce the density of defects to enable the fabrication of high-performance devices with high reliability and reproducibility.
Domain wall magnetic tunnel junction-based artificial synapses and neurons for all-spin neuromorphic hardware
Authors: Liu Long , Wang Di , Wang Dandan , Sun Yan , Lin Huai , Gong Xiliang , Zhang Yifan , Tang Ruifeng , Mai Zhihong , Hou Zhipeng , Yang Yumeng , Li Peng , Wang Lan , Luo Qing , Li Ling , Xing Guozhong , Liu Ming
Published: May 2024

We report a breakthrough in the hardware implementation of energy-efficient all-spin synapse and neuron devices for highly scalable integrated neuromorphic circuits. Our work demonstrates the successful execution of all-spin synapse and activation function generator using domain wall-magnetic tunnel junctions. By harnessing the synergistic effects of spin-orbit torque and interfacial Dzyaloshinskii-Moriya interaction in selectively etched spin-orbit coupling layers, we achieve a programmable multi-state synaptic device with high reliability. Our first-principles calculations confirm that the reduced atomic distance between 5dand 3datoms enhances Dzyaloshinskii-Moriya interaction, leading to stable domain wall pinning. Our experimental results, supported by visualizing energy landscapes and theoretical simulations, validate the proposed mechanism. Furthermore, we demonstrate a spin-neuron with a sigmoidal activation function, enabling high operation frequency up to 20 MHz and low energy consumption of 508 fJ/operation. A neuron circuit design with a compact sigmoidal cell area and low power consumption is also presented, along with corroborated experimental implementation. Our findings highlight the great potential of domain wall-magnetic tunnel junctions in the development of all-spin neuromorphic computing hardware, offering exciting possibilities for energy-efficient and scalable neural network architectures.
Dynamics underlie the drug recognition mechanism by the efflux transporter EmrE
Authors: Li Jianping , Her Ampon Sae , Besch Alida , Ramirez-Cordero Belen , Crames Maureen , Banigan James R. , Mueller Casey , Marsiglia William M. , Zhang Yingkai , Traaseth Nathaniel J.
Published: May 2024

The multidrug efflux transporter EmrE from Escherichia coli requires anionic residues in the substrate binding pocket for coupling drug transport with the proton motive force. Here, we show how protonation of a single membrane embedded glutamate residue (Glu14) within the homodimer of EmrE modulates the structure and dynamics in an allosteric manner using NMR spectroscopy. The structure of EmrE in the Glu14 protonated state displays a partially occluded conformation that is inaccessible for drug binding by the presence of aromatic residues in the binding pocket. Deprotonation of a single Glu14 residue in one monomer induces an equilibrium shift toward the open state by altering its side chain position and that of a nearby tryptophan residue. This structural change promotes an open conformation that facilitates drug binding through a conformational selection mechanism and increases the binding affinity by approximately 2000-fold. The prevalence of proton-coupled exchange in efflux systems suggests a mechanism that may be shared in other antiporters where acid/base chemistry modulates access of drugs to the substrate binding pocket.
Structure prediction of protein-ligand complexes from sequence information with Umol
Authors: Bryant Patrick , Kelkar Atharva , Guljas Andrea , Clementi Cecilia , Noé Frank
Published: May 2024

Protein-ligand docking is an established tool in drug discovery and development to narrow down potential therapeutics for experimental testing. However, a high-quality protein structure is required and often the protein is treated as fully or partially rigid. Here we develop an AI system that can predict the fully flexible all-atom structure of protein-ligand complexes directly from sequence information. We find that classical docking methods are still superior, but depend upon having crystal structures of the target protein. In addition to predicting flexible all-atom structures, predicted confidence metrics (plDDT) can be used to select accurate predictions as well as to distinguish between strong and weak binders. The advances presented here suggest that the goal of AI-based drug discovery is one step closer, but there is still a way to go to grasp the complexity of protein-ligand interactions fully. Umol is available at: https://github.com/patrickbryant1/Umol.
Intelligent wearable olfactory interface for latency-free mixed reality and fast olfactory enhancement
Authors: Liu Yiming , Jia Shengxin , Yiu Chun Ki , Park Wooyoung , Chen Zhenlin , Nan Jin , Huang Xingcan , Chen Hongting , Li Wenyang , Gao Yuyu , Song Weike , Yokota Tomoyuki , Someya Takao , Zhao Zhao , Li Yuhang , Yu Xinge
Published: May 2024

Olfaction feedback systems could be utilized to stimulate human emotion, increase alertness, provide clinical therapy, and establish immersive virtual environments. Currently, the reported olfaction feedback technologies still face a host of formidable challenges, including human perceivable delay in odor manipulation, unwieldy dimensions, and limited number of odor supplies. Herein, we report a general strategy to solve these problems, which associates with a wearable, high-performance olfactory interface based on miniaturized odor generators (OGs) with advanced artificial intelligence (AI) algorithms. The OGs serve as the core technology of the intelligent olfactory interface, which exhibit milestone advances in millisecond-level response time, milliwatt-scale power consumption, and the miniaturized size. Empowered by robust AI algorithms, the olfactory interface shows its great potentials in latency-free mixed reality (MR) and fast olfaction enhancement, thereby establishing a bridge between electronics and users for broad applications ranging from entertainment, to education, to medical treatment, and to human machine interfaces.
Quantum barriers engineering toward radiative and stable perovskite photovoltaic devices
Authors: Yeom Kyung Mun , Cho Changsoon , Jung Eui Hyuk , Kim Geunjin , Moon Chan Su , Park So Yeon , Kim Su Hyun , Woo Mun Young , Khayyat Mohammed Nabaz Taher , Lee Wanhee , Jeon Nam Joong , Anaya Miguel , Stranks Samuel D. , Friend Richard H. , Greenham Neil C. , Noh Jun Hong
Published: May 2024

Efficient photovoltaic devices must be efficient light emitters to reach the thermodynamic efficiency limit. Here, we present a promising prospect of perovskite photovoltaics as bright emitters by harnessing the significant benefits of photon recycling, which can be practically achieved by suppressing interfacial quenching. We have achieved radiative and stable perovskite photovoltaic devices by the design of a multiple quantum well structure with long (∼3 nm) organic spacers with oleylammonium molecules at perovskite top interfaces. Our L-site exchange process (L: barrier molecule cation) enables the formation of stable interfacial structures with moderate conductivity despite the thick barriers. Compared to popular short (∼1 nm) Ls, our approach results in enhanced radiation efficiency through the recursive process of photon recycling. This leads to the realization of radiative perovskite photovoltaics with both high photovoltaic efficiency (in-lab 26.0%, certified to 25.2%) and electroluminescence quantum efficiency (19.7 % at peak, 17.8% at 1-sun equivalent condition). Furthermore, the stable crystallinity of oleylammonium-based quantum wells enables our devices to maintain high efficiencies for over 1000 h of operation and >2 years of storage.
Non-thermal emission in gap-mode plasmon photoluminescence
Authors: Lemasters Robert , Manjare Manoj , Freeman Ryan , Wang Feng , Pierce Luka Guy , Hua Gordon , Urazhdin Sergei , Harutyunyan Hayk
Published: May 2024

Photoluminescence from spatially inhomogeneous plasmonic nanostructures exhibits fascinating wavelength-dependent nonlinear behaviors due to the intraband recombination of hot electrons excited into the conduction band of the metal. The properties of the excited carrier distribution and the role of localized plasmonic modes are subjects of debate. In this work, we use plasmonic gap-mode resonators with precise nanometer-scale confinement to show that the nonlinear photoluminescence behavior can become dominated by non-thermal contributions produced by the excited carrier population that strongly deviates from the Fermi-Dirac distribution due to the confinement-induced large-momentum free carrier absorption beyond the dipole approximation. These findings open new pathways for controllable light conversion using nonequilibrium electron states at the nanoscale.
The low-density lipoprotein receptor and apolipoprotein E associated with CCHFV particles mediate CCHFV entry into cells
Authors: Ritter Maureen , Canus Lola , Gautam Anupriya , Vallet Thomas , Zhong Li , Lalande Alexandre , Boson Bertrand , Gandhi Apoorv , Bodoirat Sergueï , Burlaud-Gaillard Julien , Freitas Natalia , Roingeard Philippe , Barr John N. , Lotteau Vincent , Legros Vincent , Mathieu Cyrille , Cosset François-Loïc , Denolly Solène
Published: May 2024

The Crimean-Congo hemorrhagic fever virus (CCHFV) is an emerging pathogen of the Orthonairovirus genus that can cause severe and often lethal hemorrhagic diseases in humans. CCHFV has a broad tropism and can infect a variety of species and tissues. Here, by using gene silencing, blocking antibodies or soluble receptor fragments, we identify the low-density lipoprotein receptor (LDL-R) as a CCHFV entry factor. The LDL-R facilitates binding of CCHFV particles but does not allow entry of Hazara virus (HAZV), another member of the genus. In addition, we show that apolipoprotein E (apoE), an exchangeable protein that mediates LDL/LDL-R interaction, is incorporated on CCHFV particles, though not on HAZV particles, and enhances their specific infectivity by promoting an LDL-R dependent entry. Finally, we show that molecules that decrease LDL-R from the surface of target cells could inhibit CCHFV infection. Our study highlights that CCHFV takes advantage of a lipoprotein receptor and recruits its natural ligand to promote entry into cells.
Usability and feasibility of the Test of Adherence to Inhalers (TAI) Toolkit in daily clinical practice: The BANANA study
Authors: Achterbosch Maria , van de Hei Susanne J. , Dierick Boudewijn J. H. , Kocks Janwillem W. H. , van den Berge Maarten , Kerstjens Huib A. M. , Been-Buck Sandra , Klemmeier Titia , van Dijk Liset , van Boven Job F. M.
Published: May 2024

The Test of Adherence to Inhalers (TAI) Toolkit links an adherence measurement instrument (the TAI) to proven effective interventions for different causes of non-adherence to inhaled medication. This study aimed to assess the usability and feasibility of the TAI Toolkit in clinical practice. The TAI Toolkit was piloted in eight primary and secondary care settings. Each study site included 10 patients with asthma and/or COPD and suspected non-adherence. Healthcare professionals (HCPs) recorded clinical data and TAI Toolkit outcomes. Data on usability and feasibility were collected in semi-structured interviews and with the System Usability Score (SUS). Of the included patients, 81% were non-adherent, and sporadic non-adherence was the most common (69%). The TAI Toolkit was valued with a mean SUS-score of 85.9 by the HCPs. They found the toolkit to ‘be visually attractive’, ‘easy-to-use’ and ‘give insight into patients’ adherence’, thereby offering good potential for its use in clinical practice.
Microbial polyphenol metabolism is part of the thawing permafrost carbon cycle
Authors: McGivern Bridget B. , Cronin Dylan R. , Ellenbogen Jared B. , Borton Mikayla A. , Knutson Eleanor L. , Freire-Zapata Viviana , Bouranis John A. , Bernhardt Lukas , Hernandez Alma I. , Flynn Rory M. , Woyda Reed , Cory Alexandra B. , Wilson Rachel M. , Chanton Jeffrey P. , Woodcroft Ben J. , Ernakovich Jessica G. , Tfaily Malak M. , Sullivan Matthew B. , Tyson Gene W. , Rich Virginia I. , Hagerman Ann E. , Wrighton Kelly C.
Published: May 2024

With rising global temperatures, permafrost carbon stores are vulnerable to microbial degradation. The enzyme latch theory states that polyphenols should accumulate in saturated peatlands due to diminished phenol oxidase activity, inhibiting resident microbes and promoting carbon stabilization. Pairing microbiome and geochemical measurements along a permafrost thaw-induced saturation gradient in Stordalen Mire, a model Arctic peatland, we confirmed a negative relationship between phenol oxidase expression and saturation but failed to support other trends predicted by the enzyme latch. To inventory alternative polyphenol removal strategies, we built CAMPER, a gene annotation tool leveraging polyphenol enzyme knowledge gleaned across microbial ecosystems. Applying CAMPER to genome-resolved metatranscriptomes, we identified genes for diverse polyphenol-active enzymes expressed by various microbial lineages under a range of redox conditions. This shifts the paradigm that polyphenols stabilize carbon in saturated soils and highlights the need to consider both oxic and anoxic polyphenol metabolisms to understand carbon cycling in changing ecosystems.
Self-assembling viral histones are evolutionary intermediates between archaeal and eukaryotic nucleosomes
Authors: Irwin Nicholas A. T. , Richards Thomas A.
Published: May 2024

Nucleosomes are DNA–protein complexes composed of histone proteins that form the basis of eukaryotic chromatin. The nucleosome was a key innovation during eukaryotic evolution, but its origin from histone homologues in Archaea remains unclear. Viral histone repeats, consisting of multiple histone paralogues within a single protein, may reflect an intermediate state. Here we examine the diversity of histones encoded by Nucleocytoviricota viruses. We identified 258 histones from 168 viral metagenomes with variable domain configurations including histone singlets, doublets, triplets and quadruplets, the latter comprising the four core histones arranged in series. Viral histone repeats branch phylogenetically between Archaea and eukaryotes and display intermediate functions in Escherichia coli, self-assembling into eukaryotic-like nucleosomes that stack into archaeal-like oligomers capable of impacting genomic activity and condensing DNA. Histone linkage also facilitates nucleosome formation, promoting eukaryotic histone assembly in E. coli. These data support the hypothesis that viral histone repeats originated in stem-eukaryotes and that nucleosome evolution proceeded through histone repeat intermediates.
Maritime Freight Carbon Emission in the U.S. using AIS data from 2018 to 2022
Authors: Cheng Cheng , Li Zengshuang , Yan Yuting , Cui Qiang , Zhang Yong , Liu Lei
Published: May 2024

Global maritime emissions, a 3% contributor to greenhouse gases, anticipate a surge of 90–130% by 2050. Regulatory challenges persist due to international governance gaps. Legislative strides, including the EU Emission Trading System, highlight global efforts. In the U.S., despite legislative commitment, consensus hurdles impede cross-regional carbon management. Prevailing top-down emissions estimation methods warrant scrutiny. This paper unveils U.S. maritime emissions intricacies, focusing on carbon accounting, transfer, and compensation for cargo and tanker vessels. Leveraging AIS data (2018–2022), an activity-based/bottom-up approach navigates emissions calculations, aiming to reshape understanding and foster strategic reductions. The study bridges gaps in U.S. maritime emission research, promising insights into transfer and compensation dynamics. By concentrating on high-impact vessel types, it contributes to emissions mitigation strategies, steering towards a sustainable U.S. maritime future.
Establishment of a high-content compatible platform to assess effects of monocyte-derived factors on neural stem cell proliferation and differentiation
Authors: Campo Garcia Juliana , Bueno Roemel Jeusep , Salla Maren , Martorell-Serra Ivette , Seeger Bibiane , Akbari Nilufar , Sperber Pia , Stachelscheid Harald , Infante-Duarte Carmen , Paul Friedemann , Starossom Sarah C.
Published: May 2024

During neuroinflammation, monocytes that infiltrate the central nervous system (CNS) may contribute to regenerative processes depending on their activation status. However, the extent and mechanisms of monocyte-induced CNS repair in patients with neuroinflammatory diseases remain largely unknown, partly due to the lack of a fully human assay platform that can recapitulate monocyte-neural stem cell interactions within the CNS microenvironment. We therefore developed a human model system to assess the impact of monocytic factors on neural stem cells, establishing a high-content compatible assay for screening monocyte-induced neural stem cell proliferation and differentiation. The model combined monocytes isolated from healthy donors and human embryonic stem cell derived neural stem cells and integrated both cell-intrinsic and -extrinsic properties. We identified CNS-mimicking culture media options that induced a monocytic phenotype resembling CNS infiltrating monocytes, while allowing adequate monocyte survival. Monocyte-induced proliferation, gliogenic fate and neurogenic fate of neural stem cells were affected by the conditions of monocytic priming and basal neural stem cell culture as extrinsic factors as well as the neural stem cell passage number as an intrinsic neural stem cell property. We developed a high-content compatible human in vitro assay for the integrated analysis of monocyte-derived factors on CNS repair.
In vitro and ex vivo protoscolicidal effect of poly(amidoamine) nanoemulsion against Echinococcus granulosus
Authors: Aboelsoued Dina , Toaleb Nagwa I. , Ibrahim Sally , Ibrahim Saber
Published: May 2024

Hydatidosis causes a serious health hazard to humans and animals leading to significant economic and veterinary and public health concern worldwide. The present study aimed to evaluate the in vitro and ex vivo protoscolicidal effects of synthesized poly(amidoamine), PAMAM, nanoemulsion. In this study, PAMAM was characterized through dynamic light scattering technique to investigate the particle size and zeta potential of nanoemulsified polymer. For the in vitro and ex vivo assays, we used eosin dye exclusion test and scanning electron microscope (SEM) to evaluate the effects of the prepared and characterized PAMAM nanoemulsion against protoscoleces from Echinococcus granulosus sensu lato G6 (GenBank: OQ443068.1) isolated from livers of naturally infected camels. Various concentrations (0.5, 1, 1.5 and 2 mg/mL) of PAMAM nanoemulsion at different exposure times (5, 10, 20 and 30 min) were tested against protoscolices. Our findings showed that PAMAM nanoemulsion had considerable concentration- and time-dependent protoscolicidal effect at both in vitro and ex vivo experiments. Regarding in vitro assay, PAMAM nanoemulsion had a potent protoscolicidal effect when compared with the control group with a highest protoscolicidal activity observed at the concentration of 2 mg/mL at all exposure times, such that 100% of protoscolices were killed after 20 min of exposure. Also, the mortality of protoscolices was 100% after 30 min of exposure to 1 and 1.5 mg/mL of PAMAM nanoemulsion, in vitro. Concerning ex vivo assay PAMAM nanoemulsion recorded the highest mortality rates at the concentration of 2 mg/mL (55, 99.4 and 100% at 10, 20, 30 min, respectively). Ultrastructure examination of examined protoscolices after 20 min of exposure to PAMAM nanoemulsion showed a complete loss of rostellar hooks, disruption of suckers with disorganization of hooks with partial or complete loss of them, and damage of protoscolices tegument with loss of their integrity in the form of holes and contraction of the soma region were observed in 1.5 and 2 mg/mL of PAMAM, in vitro and ex vivo, showing more damage in the in vitro conditions. It can be concluded that PAMAM nanoemulsion is a promising protoscolicidal agent offering a high protoscolicidal effect at a short exposure time. Further in vivo studies and preclinical animal trials are required to evaluate its efficacy and clinical applications against hydatid cysts.
Structure-aware machine learning strategies for antimicrobial peptide discovery
Authors: Aguilera-Puga Mariana D. C. , Plisson Fabien
Published: May 2024

Machine learning models are revolutionizing our approaches to discovering and designing bioactive peptides. These models often need protein structure awareness, as they heavily rely on sequential data. The models excel at identifying sequences of a particular biological nature or activity, but they frequently fail to comprehend their intricate mechanism(s) of action. To solve two problems at once, we studied the mechanisms of action and structural landscape of antimicrobial peptides as (i) membrane-disrupting peptides, (ii) membrane-penetrating peptides, and (iii) protein-binding peptides. By analyzing critical features such as dipeptides and physicochemical descriptors, we developed models with high accuracy (86–88%) in predicting these categories. However, our initial models (1.0 and 2.0) exhibited a bias towards α-helical and coiled structures, influencing predictions. To address this structural bias, we implemented subset selection and data reduction strategies. The former gave three structure-specific models for peptides likely to fold into α-helices (models 1.1 and 2.1), coils (1.3 and 2.3), or mixed structures (1.4 and 2.4). The latter depleted over-represented structures, leading to structure-agnostic predictors 1.5 and 2.5. Additionally, our research highlights the sensitivity of important features to different structure classes across models.