bluuebunny/crossref_metadata_2025 huggingface dataset:
A Survey on Recent Advances and Challenges in Reinforcement Learning Methods for Task-oriented Dialogue Policy Learning
Authors: Kwan Wai-Chung , Wang Hong-Ru , Wang Hui-Min , Wong Kam-Fai
Published: January 2023

Dialogue policy learning (DPL) is a key component in a task-oriented dialogue (TOD) system. Its goal is to decide the next action of the dialogue system, given the dialogue state at each turn based on a learned dialogue policy. Reinforcement learning (RL) is widely used to optimize this dialogue policy. In the learning process, the user is regarded as the environment and the system as the agent. In this paper, we present an overview of the recent advances and challenges in dialogue policy from the perspective of RL. More specifically, we identify the problems and summarize corresponding solutions for RL-based dialogue policy learning. In addition, we provide a comprehensive survey of applying RL to DPL by categorizing recent methods into five basic elements in RL. We believe this survey can shed light on future research in DPL.
AI in Human-computer Gaming: Techniques, Challenges and Opportunities
Authors: Yin Qi-Yue , Yang Jun , Huang Kai-Qi , Zhao Mei-Jing , Ni Wan-Cheng , Liang Bin , Huang Yan , Wu Shu , Wang Liang
Published: January 2023

With the breakthrough of AlphaGo, human-computer gaming AI has ushered in a big explosion, attracting more and more researchers all over the world. As a recognized standard for testing artificial intelligence, various human-computer gaming AI systems (AIs) have been developed, such as Libratus, OpenAI Five, and AlphaStar, which beat professional human players. The rapid development of human-computer gaming AIs indicates a big step for decision-making intelligence, and it seems that current techniques can handle very complex human-computer games. So, one natural question arises: What are the possible challenges of current techniques in human-computer gaming and what are the future trends? To answer the above question, in this paper, we survey recent successful game AIs, covering board game AIs, card game AIs, first-person shooting game AIs, and real-time strategy game AIs. Through this survey, we 1) compare the main difficulties among different kinds of games and the corresponding techniques utilized for achieving professional human-level AIs; 2) summarize the mainstream frameworks and techniques that can be properly relied on for developing AIs for complex human-computer games; 3) raise the challenges or drawbacks of current techniques in the successful AIs; and 4) try to point out future trends in human-computer gaming AIs. Finally, we hope that this brief review can provide an introduction for beginners and inspire insight for researchers in the field of AI in human-computer gaming.
Clinical testing of the cardiovascular effects of e-cigarette substitution for smoking: a living systematic review
Authors: La Rosa Giusy , Vernooij Robin , Qureshi Maria , Polosa Riccardo , O’Leary Renée
Published: January 2023

Some persons who smoke have substituted e-cigarettes for tobacco cigarettes, either completely or partially. What effect does this have on cardiovascular functioning? We conducted a living systematic review on human clinical studies measuring the cardiovascular effects of e-cigarette substitution for smoking. The Scopus, PubMed, and CENTRAL Cochrane Library databases were searched on January 31 and April 29, 2021. Three secondary searches and a grey literature search were conducted. Included study designs were randomized controlled trials, quasi-experimental clinical trials, and cohort studies. Risk of bias and study quality were evaluated with the JBI Critical Appraisal tools and the Oxford Catalogue of Bias. The systematic review covered 25 studies comprising 1810 participants who smoked. Twenty studies were rated at high risk of bias, and five as some concerns. A tabular synthesis by direction of effect was conducted due to heterogeneity in the data. Nearly two-thirds of the test analyses indicated that e-cigarette use had no significance difference compared with tobacco cigarettes on heart rate, blood pressure, and in other cardiovascular tests. In two studies, participants with hypertension experienced a clinically relevant reduction in systolic blood pressure after 1 year of e-cigarette use. E-cigarette substitution incurs no additional cardiovascular risks, and some possible benefits may be obtained, but the evidence is of low to very low certainty. An update search on May 30, 2022 retrieved five studies that did not alter our conclusion.

Registration PROSPERO #CRD42021239094.
Computational Analysis of the Mechanical Properties of Ta/Cu Nanocomposite Dental Implants: On the Role of Incoherent Interfaces
Authors: Kardani Arash , Montazeri Abbas , Urbassek Herbert M.
Published: January 2023

In recent years, tantalum (Ta)-based nanostructured dental implants have been widely utilized considering their exceptional biocompatibility, bioactivity, and biomechanical properties. Despite their advantages, the mechanical properties of Ta are higher than those of the adjacent jawbone, weakening the bone structure. It has been demonstrated that soft antibacterial additives such as copper (Cu) nanoparticles can tune the mechanical features of Ta-based implants to be similar to those of the adjacent bone. However, a noticeable gap in this research area is the lack of a computational model to explore the interfacial load transfer through the curved interfaces of Ta/Cu nanocomposites. Accordingly, a series of molecular dynamics simulations is employed to survey the microstructural evolution in Ta/Cu nanocomposites subjected to the uniaxial tensile loading condition at the body temperature. Additionally, to provide a complete picture of the contribution of Cu nanoparticles to the results, the mechanisms governing the plastic deformation of nanocomposite models with fine-grained and coarse-grained Ta matrix is systematically examined during the process. In summary, this work provides a comprehensive molecular dynamics simulation of the role of dislocation networks, twin formation, and their mutual interactions on the extent of the plastic zone in various Ta/Cu nanocomposite models.

Graphical Abstract
Potential of the hazelnut tree search–ELM hybrid approach in estimating yield and water productivity
Authors: Dehghanisanij Hossein , Emami Somayeh , Rezaverdinejad Vahid , Amini Abdollah
Published: January 2023

Wheat plays a vital role in the food security of society, and early estimation of its yield will be a great help to macro-decisions. For this purpose, wheat yield and water productivity (WP) by considering soil data, irrigation, fertilizer, climate, and crop characteristics and using a novel hybrid approach called hazelnut tree search algorithm (HTS) and extreme machine learning method (ELM) was examined under the drip (tape) irrigation. A dataset including 125 wheat yield data, irrigation and meteorological data of Mahabad plain located southeast of Lake Urmia, Iran, was used as input parameters for crop year 2020–2021. Eighty percentage of the data were used for training, and the remaining 20% for model testing. Nine different input scenarios were presented to estimate yield and WP. The efficiency of the proposed model was calculated with the statistical indices coefficient of determination (R2), root-mean-square error (RMSE), normalized root-mean-square error, and efficiency criterion. Sensitivity analysis result showed that the parameters of irrigation, rainfall, soil moisture, and crop variety provide better results for modeling. There was good agreement between the practical values (field management data) and the estimated values with the HTS–ELM model. The results also showed that the HTS–ELM method is very efficient in selecting the best input combination with R2 = 0.985 and RMSE = 0.005. In general, intelligent hybrid methods can enable optimal and economical use of water and soil resources.
Genetic mutations affecting mitochondrial function in cancer drug resistance
Authors: Lee Chanhaeng , Park Sang‑Hee , Yoon Sungjoo Kim
Published: January 2023

Mitochondria are organelles that serve as a central hub for physiological processes in eukaryotes, including production of ATP, regulation of calcium dependent signaling, generation of ROS, and regulation of apoptosis. Cancer cells undergo metabolic reprogramming in an effort to support their increasing requirements for cell survival, growth, and proliferation, and mitochondria have primary roles in these processes. Because of their central function in survival of cancer cells and drug resistance, mitochondria are an important target in cancer therapy and many drugs targeting mitochondria that target the TCA cycle, apoptosis, metabolic pathway, and generation of ROS have been developed. Continued use of mitochondrial-targeting drugs can lead to resistance due to development of new somatic mutations. Use of drugs is limited due to these mutations, which have been detected in mitochondrial proteins. In this review, we will focus on genetic mutations in mitochondrial target proteins and their function in induction of drug-resistance.
Reducing congestion and emissions via roadside unit deployment under mixed traffic flow
Authors: Liu Yuhao , Chen Zhibin , Gong Siyuan , Liu Han
Published: January 2023

It is expected that for a long time the future road traffic will be composed of both regular vehicles (RVs) and connected autonomous vehicles (CAVs). As a vehicle-to-infrastructure technology dedicated to facilitating CAV under the mixed traffic flow, roadside units (RSUs) can also improve the quality of information received by CAVs, thereby influencing the routing behavior of CAV users. This paper explores the possibility of leveraging the RSU deployment to affect the route choices of both CAVs and RVs and the adoption rate of CAVs so as to reduce the network congestion and emissions. To this end, we first establish a logit-based stochastic user equilibrium model to capture drivers’ route choice and vehicle type choice behaviors provided the RSU deployment plan is given. Particularly, CAV users’ perception error can be reduced by higher CAV penetration and denser RSUs deployed on the road due to the improved information quality. With the established equilibrium model, the RSU deployment problem is then formulated as a mathematical program with equilibrium constraints. An active-set algorithm is presented to solve the deployment problem efficiently. Numerical results suggest that an optimal RSU deployment plan can effectively drive the system towards one with lower network delay and emissions.
Spatiotemporal change detection of land use land cover (LULC) in Fashiakhali wildlife sanctuary (FKWS) impact area, Bangladesh, employing multispectral images and GIS
Authors: Hossain Md. Sazzad , Khan Md. Asif Haider , Oluwajuwon Tomiwa Victor , Biswas Jayanta , Rubaiot Abdullah S. M. , Tanvir Md. Seikh Sadiul Islam , Munira Sirajum , Chowdhury Md. Naif Ahmed
Published: January 2023

Land cover change has posed significant concerns to biodiversity and climate change in Bangladesh and globally. Despite the country’s designation of forest regions as protected areas to conserve their valuable resources, deforestation and forest conversion remained unabated. Fashiakhali Wildlife Sanctuary (FKWS), a protected area in the Chittagong Hill Tracts, and its surrounding forested impact area have experienced considerable changes over the years, yet are deficient in extensive assessment. This study evaluated the land use land cover (LULC) changes in the FKWS impact area over almost 3 decades (1994–2021) using multispectral remotely sensed data. The Landsat images of 1994, 2001, 2010, and 2021 were classified using a maximum likelihood algorithm and analyzed for change detection. The comparative potential of vegetation indices, including Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI), in forest cover assessment, and the relationship between Land Surface Temperature (LST) and NDVI was also assessed. A significant forest cover loss of around 1117.17 ha (16%) was recorded in the FKWS impact area between 1994 and 2021, with the hugest proportion of 867.78 ha (12.24%) deforested in the first period (1994–2001). Agricultural land also declined by 593.73 ha (8.37%) within the entire period, despite its initial increase of 392.04 ha (5.53%) between 2001 and 2010, being the primary driver of earlier deforestation. However, in the recent decade (2010–2021), settlement expansion of 963.90 ha (13.59%) due to massive human migration in the area contributed to the most remarkable overall land cover change of 1731.51 ha (24.42%). Furthermore, NDVI provided a better and more accurate forest cover assessment than SAVI and was recommended to aid in the quick evaluation and monitoring of the future impacts of agriculture, settlement, and other sorts of land use on the forest cover. In tandem with the widely acknowledged issue of increased temperature due to climate change, an absolute negative correlation was found between the NDVI and LST, confirming the negative impact of climate change on forest loss in the FKWS impact area.
Recurring heavy rainfall resulting in degraded-upgraded phases in soil microbial networks that are reflected in soil functioning
Authors: Stamou George P. , Monokrousos Nikolaos , Papapostolou Anastasia , Papatheodorou Effimia M.
Published: January 2023

• We assess the recovery of microbial networks underneath crust to repeated rainfall.

• The network fragmentation after the second heavy rain was milder than at the first one.

• Cohesive networks were related to high enzyme activity involved in C, N, and P cycles.

• Loose networks were related to high Ca, K, Mg, NH4 and organic N.

• The network in dry-crusted soils collapsed after the second heavy rain.

Biological soil crusts (BSCs) are an important multi-trophic component of arid ecosystems in the Mediterranean region. In a mesocosm experiment, the authors investigated how the network of interactions among the members of the soil microbial communities in four types of soil sample responded when soils were exposed to two simulated extreme rain events. The four types of soil samples were: covered by Cladonia rangiformis and previously hydrated (+BSC+H), covered by C. rangiformis and dried (+BSC−H), uncovered and hydrated (−BSC+H), uncovered and dried (−BSC−H). Network analysis was based on the co-occurrence patterns of microbes; microbes were assessed by the phospholipid fatty acids analysis. The authors further explored the relations between networks’ metrics and soil functions denoted by enzymatic activity and soil chemical variables. All networks exhibited Small world properties, moderate values of clustering coefficient and eigen centrality, indicating the lack of hub nodes. The networks in −BSC−H soils appeared coherent during the pre-rain phases and they became modular after rains, while those in +BSC−H soils kept their connectivity till the second rain but this then collapsed. The network metrics that were indicative of cohesive networks tended to be related to enzyme activity while those that characterized the loose networks were related to Ca, K, Mg, NH
4
+
and organic N. In all mesocosms except for +BSC−H, networks’ fragmentation after the second heavy rain was milder than after the first one, supporting the idea of community acclimatization. The response of microbial networks to heavy rains was characterized by the tendency to exhibit degradation-reconstruction phases. The network collapse in the crusted only mesocosms showed that the communities beneath crusts in arid areas were extremely vulnerable to recurring heavy rain events.
Implementation of new indicators of pediatric malnutrition and comparison to previous indicators
Authors: Ezzat Mai Adnan , Albassam Ebtsam Mohmmed , Aldajani Eman Abdullah , Alaskar Raneem Abdulaziz , Devol Edward Bentz
Published: January 2023

Background:

Early identification of childhood malnutrition is imperative to improve overall health outcomes, and more importantly, to start early intervention to decrease the risk of future complications. This study aimed to evaluate new malnutrition Z-score growth indicators for detecting pediatric malnutrition and degrees of severity and compare their accuracy with that of growth chart centiles.

Patients and Methods:

This retrospective study included 475 pediatric patients from several pediatric nutrition clinics for six months. The participant's weight, height, age, and growth parameters were recorded using both traditional growth charts (centiles) and updated malnutrition indicators (z-scores). The percentage and degree of malnutrition using centiles and Z-scores were compared.

Results:

In children aged <2 years, the percentage of malnutrition was 4.7% higher when measured using new malnutrition indicators (weight-for-length Z-score) compared with (weight-for-length centiles). Our results also showed 9.6% higher number of malnourished children >2 years of age when BMI-for-age Z-score was used compared to weight-for-height centiles while there were 15.8% higher malnourished children when BMI-for-age Z-score was compared to BMI-for-age centiles for the same group. We found a significant difference (X2 = 202.548, P=<.0001) between the degree of malnutrition in children aged >2 years using BMI-for-age Z-score (normal vs. malnourished) and the degree of malnutrition using BMI centiles (normal vs. malnourished). Approximately 34% of the children classified as normal using centiles were classified as malnourished using Z-scores. Comparing the degrees of Malnutrition, approximately 23% (45 of 196) of children classified as normal based on centiles were classified as having mild malnutrition when Z-scores were used, and 42% (80 of 192) of children who were classified as having mild malnutrition based on centiles were classified as having moderate malnutrition when Z-scores were used.

Conclusions:

In our study, a higher percentage of children showed malnutrition when assessed using the Z-score (BMI-for-age for children >2 years/weight-for-length for children <2 years of age) than the centiles growth chart.
Kickstarting Italian Opera in the Andes
Authors: Izquierdo König José Manuel
Published: January 2023

During the 19th century, Italian opera became truly transatlantic and its rapid expansion is one of the most exciting new areas of study in music and the performing arts. Beyond the Atlantic coasts, opera searched for new spaces to expand its reach. This Element discusses about the Italian opera in Andean countries like Chile, Peru, Ecuador and Bolivia during the 1840s and focuses on opera as a product that both challenged and was challenged in the Andes by other forms of performing arts, behaviours, technologies, material realities, and business models.
Understanding the Old Hispanic Office
Authors: Hornby Emma , Ihnat Kati , Maloy Rebecca , Rojo Carrillo Raquel
Published: January 2023

Based on highly original archival and palaeographical research, this is the first methodological and factual primer in English on the distinctive liturgical tradition of early medieval Spain. It provides clear and approachable blueprints for future work on the description and analysis (musical, theological and cultural) of this and other liturgies. For non-specialists, the authors introduce the main features of Old Hispanic liturgy, its manuscripts, its services and its liturgical genres. For specialists, they model a variety of ways to work with the Old Hispanic materials in depth, incorporating notational, musical, theological and historical perspectives. For those interested in musical notation, the book lays out a method for working with unpitched neumes, with illustrative results, that will inspire and challenge others working on monophonic chant. For historians and liturgists, the texts and melodies are analysed in combination with the theological context that informed their creation.
The Utility of RGB Color for Discrimination of Lunar Maturity and Composition
Authors: Blewett David T. , Choi Tiffanie X. , Zheng YongChun , Cloutis Edward A.
Published: January 2023

We explore the extent to which red‐green‐blue (RGB) color images, such as those produced by a complementary metal oxide semiconductor (CMOS) Bayer‐filter camera, can be utilized for studying the maturity and composition of the lunar surface. RGB filters typically are quite broad, with considerable overlap among the three colors. Convolution of laboratory spectra for lunar samples to the RGB responsivities of the Chang'E‐3 rover's Panoramic Camera allowed determination of the correlations between color ratios (B/R, B/G, and G/R) and the sample maturity (Is/FeO) or composition (wt.% FeO or TiO2). In general, color ratios decrease as Is/FeO increases. When separate sample categories are considered, we find that the B/R ratio is a good predictor of Is/FeO for low‐Ti mare, low‐Fe highland, and moderate‐Fe highland soils. For high‐Ti mare soils, Is/FeO has little influence on the B/R ratio (due to the spectral effects of abundant ilmenite), and hence the ratio cannot be used to determine maturity. We also find that color ratios have no useful correlation with sample wt.% FeO or TiO2. Thus, in locations excluding the high‐Ti maria, RGB color data could be used to estimate soil maturity. We outline a concept for a multispectral imager based on a CMOS sensor with a Bayer‐like pattern of custom‐wavelength filters chosen specifically for lunar science applications.
Thermally Induced Microcracks in Granite and Their Effect on the Macroscale Mechanical Behavior
Authors: Xu J. J. , Zhang Y. H. , Rutqvist J. , Hu M. S. , Wang Z. Z. , Tang X. H.
Published: January 2023

Understanding the thermal effects on rock is critical for the exploration of geothermal resources and the temperature‐driven evolution of Earth. The macroscale mechanical behavior of granite under thermal loading can be complicated due to microcracking and the heterogeneity of minerals. In this study, the thermally induced microcrack propagation of granite was first observed in real time by an ultrahigh‐temperature instrument on an optical microscope. The previous investigation believed that the α–β quartz transition at approximately 573°C leads to a sharp decrease in macroscale mechanical behavior. However, the present experimental results revealed that microcracks initiate at 300°C and coalesce between 400 and 600°C, which is the main reason for the sharp decrease in macroscale mechanical properties of granite. Additionally, an accurate grain‐based model based on the mineralogical morphology of granite samples adopted mechanical parameters of minerals obtained from microscale rock mechanical techniques. It is able to well reproduce the process of microcracking and the strength evolution of granite during heating. The numerical results show that the heterogeneity of thermal expansion and mechanical properties of minerals produce local thermal stress concentrations in granite. The uneven tensile‐compressive stress between feldspar and quartz and the shear stress around biotite result in the initiation and propagation of microcracks. The present work is potentially useful for understanding and predicting the mechanical behavior of granites under thermal loading with different mineral compositions and microstructures.
Multi‐Year Analysis of Rain‐Snow Levels at Marquette, Michigan
Authors: Shates J. A. , Pettersen C. , L’Ecuyer T. S. , Kulie M. S.
Published: January 2023

This study uses observations from a ground‐based instrument suite to investigate the rain‐snow level (RSL) in stratiform rainfall from January 2014 to April 2020 in the Upper Great Lakes Region. The height above the surface where ice melts to rain, the rain‐snow level, influences microphysical assumptions in remote sensing precipitation retrievals and the ability of space‐based radar to discriminate surface precipitation phase because of ground clutter. The instrument suite is installed at the Marquette, MI (MQT) National Weather Service station adjacent to Lake Superior. Rain events and the RSLs are studied through a ground‐based vertically profiling radar (Micro Rain Radar), a custom NASA‐developed video disdrometer (Precipitation Imaging Package), and reanalysis products from ECMWF ERA5 and NASA MERRA‐2. Distinct macro and microphysical characteristics are observed in precipitation events with shallow RSLs (<1.8 km above ground level [AGL]) and intermediate RSLs (>1.8 km AGL). Intermediate RSLs correspond to rain events with relatively higher rain rates and a higher concentration of small drops in the drop size distributions (DSDs). Shallow RSL DSDs contain relatively higher concentrations of large drops with lower fall speeds suggesting that partially melted snowflakes may be reaching the surface. Reflectivity‐rain‐rate relationships are also impacted by microphysical differences associated with RSL regimes. Radar‐detected RSLs agree with reanalysis‐derived melt levels‐especially at wet‐bulb isotherms of 0.5°C and 1°C. Seasonal differences such as shallow RSLs in winter, fall, and spring have subsequent implications for satellite detectability.
Toward Better Constrained Scattering Models for Natural Ice Crystals in the Visible Region
Authors: Xu Guanglang , Waitz Fritz , Wagner Shawn , Nehlert Franziska , Schnaiter Martin , Järvinen Emma
Published: January 2023

In this work, we introduce a method for constraining the optical scattering models of natural ice crystals based on in‐situ measurements. Specifically the measured angular scattering functions for ice crystals can be used to compute a set of the asymmetry parameter (g) and the corresponding complexity parameter (Cp). It is demonstrated that the g‐Cp relation can give valuable information on the morphology of ice crystal. The validity of the methods is shown from theoretical perspectives and the geometric‐optics ray‐tracing simulations. As an application, we investigate rimed ice crystals from in‐situ measurements and found that (a) the Cp parameter is very well correlated with the surface riming degree and (b) only those models with both roughness and internal scattering can explain the observed g‐Cp relation for rimed particles.
Age‐Depth Models for Tropical Marine Hemipelagic Deposits Improve Significantly When Proxy‐Based Information on Sediment Composition Is Included
Authors: Peeters F. J. C. , van der Lubbe H. J. L. , Scussolini P.
Published: January 2023

Accurate age‐depth models for marine sediment cores are crucial for understanding paleo‐oceanographic and ‐climatic changes derived from these archives. To date, information on bulk sediment composition is largely ignored as a potential source of information to improve age‐depth models. In this study, we explore how bulk sediment composition can be qualitatively used to improve age‐depth models. We developed the BomDia algorithm, which produces age‐depth models with realistic sediment accumulation rates that co‐vary in harmony with the bulk sediment composition. We demonstrate that changes in the marine versus terrigenous sediment deposition, based on bulk sediment composition, can be used to significantly improve age‐depth models of hemipelagic marine deposits. Based on two marine records—each containing more than 20 radiocarbon (AMS 14C) dated levels—we show that the mean error of prediction of unused AMS 14C ages significantly improves from 3.9% using simple linear interpolation, to 2.4% (p = 0.003), when bulk sediment composition is included. The BomDia age‐depth modeling approach provides a powerful statistical tool to assess the validity of age control points used and also may assist in the detection of hiatuses. Testing and further development of the BomDia algorithm may be needed for application in depositional settings other than tropical hemipelagic.
Estimation of Groundwater Flow Rate by an Actively Heated Fiber Optics Based Thermal Response Test in a Grouted Borehole
Authors: Zhang Bo , Gu Kai , Bayer Peter , Qi Haibo , Shi Bin , Wang Baojun , Jiang Yuehua , Zhou Quanping
Published: January 2023

The thermal response test (TRT) in an aquifer establishes a relationship between the groundwater flow rate and the recorded temperature response curve of temporal ground heating. A major challenge for achieving a mature hydrogeological field test is to minimize borehole effects by smart practical solutions of in situ heating and temperature sensing. When borehole effects are substantial, concepts are needed to separate their contribution to the recorded signal. This is especially the case when heating and sensing devices are installed in grouted boreholes as permanent testing stations. Interpretation of a recorded response curve thus means solving a transient heat transfer problem with radial conduction through composite media. Here, a series of numerical models are set up to study the effect of the grout and the jacket of an actively heated fiber‐optic cable on the simulated thermal response measured along a heated borehole. The findings are utilized to further develop existing groundwater flow rate estimation procedures based on the moving infinite line source model. The developed approach is demonstrated in a case study in a borehole near a bank collapse site that penetrates different aquifer layers. Accordingly, significant local groundwater flow rates (9 × 10−7–5 × 10−6 m·s−1) are found that vary with depth. The values derived by the TRT interpretation closely match the expected rates (2 × 10−6–7 × 10−6 m·s−1), which supports the good applicability of the estimation procedure in the field.
Changes in interactions over ecological time scales influence single-cell growth dynamics in a metabolically coupled marine microbial community
Authors: Daniels Michael , van Vliet Simon , Ackermann Martin
Published: January 2023

Microbial communities thrive in almost all habitats on earth. Within these communities, cells interact through the release and uptake of metabolites. These interactions can have synergistic or antagonistic effects on individual community members. The collective metabolic activity of microbial communities leads to changes in their local environment. As the environment changes over time, the nature of the interactions between cells can change. We currently lack understanding of how such dynamic feedbacks affect the growth dynamics of individual microbes and of the community as a whole. Here we study how interactions mediated by the exchange of metabolites through the environment change over time within a simple marine microbial community. We used a microfluidic-based approach that allows us to disentangle the effect cells have on their environment from how they respond to their environment. We found that the interactions between two species—a degrader of chitin and a cross-feeder that consumes metabolic by-products—changes dynamically over time as cells modify their environment. Cells initially interact positively and then start to compete at later stages of growth. Our results demonstrate that interactions between microorganisms are not static and depend on the state of the environment, emphasizing the importance of disentangling how modifications of the environment affects species interactions. This experimental approach can shed new light on how interspecies interactions scale up to community level processes in natural environments.
Leveraging molecular structure and bioactivity with chemical language models for de novo drug design
Authors: Moret Michael , Pachon Angona Irene , Cotos Leandro , Yan Shen , Atz Kenneth , Brunner Cyrill , Baumgartner Martin , Grisoni Francesca , Schneider Gisbert
Published: January 2023

Generative chemical language models (CLMs) can be used for de novo molecular structure generation by learning from a textual representation of molecules. Here, we show that hybrid CLMs can additionally leverage the bioactivity information available for the training compounds. To computationally design ligands of phosphoinositide 3-kinase gamma (PI3Kγ), a collection of virtual molecules was created with a generative CLM. This virtual compound library was refined using a CLM-based classifier for bioactivity prediction. This second hybrid CLM was pretrained with patented molecular structures and fine-tuned with known PI3Kγ ligands. Several of the computer-generated molecular designs were commercially available, enabling fast prescreening and preliminary experimental validation. A new PI3Kγ ligand with sub-micromolar activity was identified, highlighting the method’s scaffold-hopping potential. Chemical synthesis and biochemical testing of two of the top-ranked de novo designed molecules and their derivatives corroborated the model’s ability to generate PI3Kγ ligands with medium to low nanomolar activity for hit-to-lead expansion. The most potent compounds led to pronounced inhibition of PI3K-dependent Akt phosphorylation in a medulloblastoma cell model, demonstrating efficacy of PI3Kγ ligands in PI3K/Akt pathway repression in human tumor cells. The results positively advocate hybrid CLMs for virtual compound screening and activity-focused molecular design.
In vivo detection of bile duct pre-cancer with endoscopic light scattering spectroscopy
Authors: Pleskow Douglas K. , Sawhney Mandeep S. , Upputuri Paul K. , Berzin Tyler M. , Coughlan Mark F. , Khan Umar , Glyavina Maria , Zhang Xuejun , Chen Liming , Sheil Conor J. , Cohen Jonah M. , Vitkin Edward , Zakharov Yuri N. , Itzkan Irving , Zhang Lei , Qiu Le , Perelman Lev T.
Published: January 2023

Bile duct cancer is the second most common primary liver cancer, with most diagnoses occurring in the advanced stages. This leads to a poor survival rate, which means a technique capable of reliably detecting pre-cancer in the bile duct is urgently required. Unfortunately, radiological imaging lacks adequate accuracy for distinguishing dysplastic and benign biliary ducts, while endoscopic techniques, which can directly assess the bile duct lining, often suffer from insufficient sampling. Here, we report an endoscopic optical light scattering technique for clinical evaluation of the malignant potential of the bile duct. This technique employs an ultraminiature spatial gating fiber optic probe compatible with cholangioscopes and endoscopic retrograde cholangiopancreatography (ERCP) catheters. The probe allowed us to investigate the internal cellular composition of the bile duct epithelium with light scattering spectroscopy (LSS) and phenotypic properties of the underlying connective tissue with diffuse reflectance spectroscopy (DRS). In a pilot in vivo double-blind prospective study involving 29 patients undergoing routine ERCP procedures, the technique detected malignant transformation with 97% accuracy, showing that biliary duct pre-cancer can be reliably identified in vivo non-invasively.
Subthalamic beta bursts correlate with dopamine-dependent motor symptoms in 106 Parkinson’s patients
Authors: Lofredi Roxanne , Okudzhava Liana , Irmen Friederike , Brücke Christof , Huebl Julius , Krauss Joachim K. , Schneider Gerd-Helge , Faust Katharina , Neumann Wolf-Julian , Kühn Andrea A.
Published: January 2023

Pathologically increased beta power has been described as a biomarker for Parkinson’s disease (PD) and related to prolonged bursts of subthalamic beta synchronization. Here, we investigate the association between subthalamic beta dynamics and motor impairment in a cohort of 106 Parkinson’s patients in the ON- and OFF-medication state, using two different methods of beta burst determination. We report a frequency-specific correlation of low beta power and burst duration with motor impairment OFF dopaminergic medication. Furthermore, reduction of power and burst duration correlated significantly with symptom alleviation through dopaminergic medication. Importantly, qualitatively similar results were yielded with two different methods of beta burst definition. Our findings validate the robustness of previous results on pathological changes in subcortical oscillations both in the frequency- as well as in the time-domain in the largest cohort of PD patients to date with important implications for next-generation adaptive deep brain stimulation control algorithms.
Design of a hydroxy channel based on the selectivity of water permeation via ions exclusion
Authors: Ghahari Afsaneh , Raissi Heidar , Farzad Farzaneh , Pasban Samaneh
Published: January 2023

The Artificial water channels (AWCs) encapsulate water wires or clusters, analogous to natural porins, and offer iterative and continuous hydrogen bonding that plays an essential role in their stabilization. During the last few years, significant progress has been made in AWCs characterization and synthesis, and bridging these advancements to practical development remains a unique challenge. In this study, the possibility of high water selectivity and permeability, as well as the stability of the AWCs channel, is examined via classical molecular dynamic (MD) simulations and well-tempered metadynamics (Wt-metaD) simulations. The results of MD simulations demonstrated that AWCs could provide paths for rapid and selective water permeation via the formation of water-wire networks. Moreover, our findings revealed that the AWC is stable during the simulation time and non-bonded interactions, especially hydrogen bonding, have an essential role in forming a stable OH channel for transporting water molecules. However, the obtained water fluxes (L m−2 h−1) using nanofiltration AWC give us a high flux value, 19.08 (L m−2 h−1), 17.96, and 20.2 (L m−2 h−1), for AWC/ NO3−, AWC/Mg2+, and AWC/Ca2+, respectively. Well-tempered metadynamics simulations of water transport in the OH channel also report similar activation energy values and provide molecular-scale details of the mechanism for water entry into these channels. The free energy values for the AWC/water complexes at their global minima are about ~−241.912, ~−223.479, and ~−255.98 kJ mol−1 in systems AWC/NO3−, AWC/Mg2+, and AWC/Ca2+, respectively.
Advancing thermal performance through vortex generators morphing
Authors: Ali Samer , Dbouk Talib , Wang Guanghui , Wang Dingbiao , Drikakis Dimitris
Published: January 2023

The design of rigid vortex generators (RVG) influences the thermal performance of various technologies. We employed Discrete Adjoint-Based Optimization to show the optimal development of vortex generators. Under turbulent flow conditions, different bi-objective functions on the RVG design were examined. Specifically, we aimed at an optimal RVG shape that minimizes the pressure drop and maximizes the local heat transfer in a rectangular channel. We show that an optimal design of an RVG can be obtained using computational fluid dynamics in conjunction with the Pareto Front at a computational cost of the order ~$$O(10^{-1})$$

O
(

10

-
1

)

. We obtained three essential vortex generator shapes based on the RVG morphing technique. Compared to the baseline geometry of a delta winglet pair DWP, the first morphed design reduced the pressure drop by $$39\%$$

39
%

, however, at the expense of a $$21\%$$

21
%

reduction in the Nusselt number. The second vortex generator design enhanced the heat transfer by $$18\%$$

18
%

, however, at the cost of a significant increase in pressure drop of about $$40\%$$

40
%

. The final morphed design achieved the highest thermal performance factor of 1.28, representing a heat transfer enhancement of $$6\%$$

6
%

with a moderate increase in pressure drop of about $$13\%$$

13
%

compared to DWP vortex generators. Furthermore, we investigated the effect of introducing different size holes on the mass reduction of vortex generators and their thermal performances. The mass of vortex generators can be reduced by $$9\%$$

9
%

and with an increase of $$7\%$$

7
%

in thermal performance factor concerning the DWP baseline. The findings of this study will lead to highly efficient lightweight heat exchangers.
Spatial integration framework of solar, wind, and hydropower energy potential in Southeast Asia
Authors: Sakti Anjar Dimara , Rohayani Pitri , Izzah Nurusshobah Ainul , Toya Nur Afrizal , Hadi Pradita Octoviandiningrum , Octavianti Thanti , Harjupa Wendi , Caraka Rezzy Eko , Kim Yunho , Avtar Ram , Puttanapong Nattapong , Lin Chao-Hung , Wikantika Ketut
Published: January 2023

Amid its massive increase in energy demand, Southeast Asia has pledged to increase its use of renewable energy by up to 23% by 2025. Geospatial technology approaches that integrate statistical data, spatial models, earth observation satellite data, and climate modeling can be used to conduct strategic analyses for understanding the potential and efficiency of renewable energy development. This study aims to create the first spatial model of its kind in Southeast Asia to develop multi-renewable energy from solar, wind, and hydropower, further broken down into residential and agricultural areas. The novelty of this study is the development of a new priority model for renewable energy development resulting from the integration of area suitability analysis and the estimation of the amount of potential energy. Areas with high potential power estimations for the combination of the three types of energy are mostly located in northern Southeast Asia. Areas close to the equator, have a lower potential than the northern countries, except for southern regions. Solar photovoltaic (PV) plant construction is the most area-intensive type of energy generation among the considered energy sources, requiring 143,901,600 ha (61.71%), followed by wind (39,618,300 ha; 16.98%); a combination of solar PV and wind (37,302,500 ha; 16%); hydro (7,665,200 ha; 3.28%); a combination of hydro and solar PV (3,792,500 ha; 1.62%); and a combination of hydro and wind (582,700 ha; 0.25%). This study is timely and important because it will inform policies and regional strategies for transitioning to renewable energy, with consideration of the different characteristics present in Southeast Asia.
Overexpression of the NEK9–EG5 axis is a novel metastatic marker in pathologic stage T3 colon cancer
Authors: Kim Meejeong , Jeong Hui Jeong , Ju Hyun-min , Song Ji-young , Jang Se Jin , Choi Jene
Published: January 2023

NEK9 is a key player in the NEK9–EG5 axis for microtubule polymerization, chromosome alignment, and mitosis. In present study, we investigated the altered expression of the NEK9, EG5 and acetyl-α-tubulin as well as common epithelial–mesenchymal transition (EMT) markers (E-cadherin, vimentin, claudin-1, and β-catenin) through the immunohistochemistry analysis of 138 patients with pathologic T3 (pT3) stage colon cancers, and evaluated their metastatic potential. NEK9 expression showed an association with distant metastasis (P = 0.032) and was an independent predictive factor for distant metastasis (HR = 3.365, P < 0.001) by multivariate analysis, which was more significant than either the regional nodal metastasis (HR = 2.496, P = 0.007) or lymphovascular invasion (HR = 2.090, P = 0.153). Positive correlations were observed between NEK9 and EG5 or acetyl-α-tubulin (r = 0.236 and P = 0.007; r = 0.181 and P = 0.038, respectively) and concordant overexpression of the NEK9–EG5 axis was further confirmed in colon cancer cell lines. These findings collectively suggest that the overexpression of the NEK9–EG5 axis is present and associated with distant metastasis in colon cancer. These biomarkers might be useful for predicting metastatic potential among the patients with pT3 colon cancers.
Analysis of critical protein–protein interactions of SARS-CoV-2 capping and proofreading molecular machineries towards designing dual target inhibitory peptides
Authors: Arabi-Jeshvaghani Fatemeh , Javadi‐Zarnaghi Fatemeh , Ganjalikhany Mohamad Reza
Published: January 2023

In recent years, the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as the cause of the coronavirus disease (COVID-19) global pandemic, and its variants, especially those with higher transmissibility and substantial immune evasion, have highlighted the imperative for developing novel therapeutics as sustainable solutions other than vaccination to combat coronaviruses (CoVs). Beside receptor recognition and virus entry, members of the SARS-CoV-2 replication/transcription complex are promising targets for designing antivirals. Here, the interacting residues that mediate protein–protein interactions (PPIs) of nsp10 with nsp16 and nsp14 were comprehensively analyzed, and the key residues’ interaction maps, interaction energies, structural networks, and dynamics were investigated. Nsp10 stimulates both nsp14’s exoribonuclease (ExoN) and nsp16’s 2′O-methyltransferase (2′O-MTase). Nsp14 ExoN is an RNA proofreading enzyme that supports replication fidelity. Nsp16 2′O-MTase is responsible for the completion of RNA capping to ensure efficient replication and translation and escape from the host cell’s innate immune system. The results of the PPIs analysis proposed crucial information with implications for designing SARS-CoV-2 antiviral drugs. Based on the predicted shared protein–protein interfaces of the nsp16-nsp10 and nsp14-nsp10 interactions, a set of dual-target peptide inhibitors was designed. The designed peptides were evaluated by molecular docking, peptide–protein interaction analysis, and free energy calculations, and then further optimized by in silico saturation mutagenesis. Based on the predicted evolutionary conservation of the interacted target residues among CoVs, the designed peptides have the potential to be developed as dual target pan-coronavirus inhibitors.
IL-1β neutralization prevents diastolic dysfunction development, but lacks hepatoprotective effect in an aged mouse model of NASH
Authors: Kucsera Dániel , Tóth Viktória E. , Sayour Nabil V. , Kovács Tamás , Gergely Tamás G. , Ruppert Mihály , Radovits Tamás , Fábián Alexandra , Kovács Attila , Merkely Béla , Ferdinandy Péter , Varga Zoltán V.
Published: January 2023

Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1β targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional—and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH. In conclusion, IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.