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Introduction: A multitude of findings from cell cultures and animal studies are available to support the anti-cancer properties of cannabidiol (CBD). Since CBD acts on multiple molecular targets, its clinical adaptation, especially in combination with cancer immunotherapy regimen remains a serious concern.
Methods: Considering this, we extensively studied the effect of CBD on the cytokine-induced killer (CIK) cell immunotherapy approach using multiple non-small cell lung cancer (NSCLC) cells harboring diverse genotypes.
Results: Our analysis showed that, a) The Transient Receptor Potential Cation Channel Subfamily V Member 2 (TRPV2) channel was intracellularly expressed both in NSCLC cells and CIK cells. b) A synergistic effect of CIK combined with CBD, resulted in a significant increase in tumor lysis and Interferon gamma (IFN-g) production. c) CBD had a preference to elevate the CD25+CD69+ population and the CD62L_CD45RA+terminal effector memory (EMRA) population in NKT-CIK cells, suggesting early-stage activation and effector memory differentiation in CD3+CD56+ CIK cells. Of interest, we observed that CBD enhanced the calcium influx, which was mediated by the TRPV2 channel and elevated phosphor-Extracellular signal-Regulated Kinase (p-ERK) expression directly in CIK cells, whereas ERK selective inhibitor FR180204 inhibited the increasing cytotoxic CIK ability induced by CBD. Further examinations revealed that CBD induced DNA double-strand breaks via upregulation of histone H2AX phosphorylation in NSCLC cells and the migration and invasion ability of NSCLC cells suppressed by CBD were rescued using the TRPV2 antagonist (Tranilast) in the absence of CIK cells. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation. We further investigated the epigenetic effects of this synergy and found that adding CBD to CIK cells decreased the Long Interspersed Nuclear Element-1 (LINE-1) mRNA expression and the global DNA methylation level in NSCLC cells carrying KRAS mutation.
Conclusions: Taken together, CBD holds a great potential for treating NSCLC with CIK cell immunotherapy. In addition, we utilized NSCLC with different driver mutations to investigate the efficacy of CBD. Our findings might provide evidence for CBD-personized treatment with NSCLC patients.
Self-motion perception is a multi-sensory process that involves visual, vestibular, and other cues. When perception of self-motion is induced using only visual motion, vestibular cues indicate that the body remains stationary, which may bias an observer’s perception. When lowering the precision of the vestibular cue by for example, lying down or by adapting to microgravity, these biases may decrease, accompanied by a decrease in precision. To test this hypothesis, we used a move-to-target task in virtual reality. Astronauts and Earth-based controls were shown a target at a range of simulated distances. After the target disappeared, forward self-motion was induced by optic flow. Participants indicated when they thought they had arrived at the target’s previously seen location. Astronauts completed the task on Earth (supine and sitting upright) prior to space travel, early and late in space, and early and late after landing. Controls completed the experiment on Earth using a similar regime with a supine posture used to simulate being in space. While variability was similar across all conditions, the supine posture led to significantly higher gains (target distance/perceived travel distance) than the sitting posture for the astronauts pre-flight and early post-flight but not late post-flight. No difference was detected between the astronauts’ performance on Earth and onboard the ISS, indicating that judgments of traveled distance were largely unaffected by long-term exposure to microgravity. Overall, this constitutes mixed evidence as to whether non-visual cues to travel distance are integrated with relevant visual cues when self-motion is simulated using optic flow alone.
Protocol for conducting advanced cyclic tests in lithium-ion batteries to estimate capacity fade
(2024)
Using advanced cyclic testing techniques improves accuracy in estimating capacity fade and incorporates real-world scenarios in battery cycle aging assessment. Here, we present a protocol for conducting cyclic tests in lithium-ion batteries to estimate capacity fade. We describe steps for implementing strategies for accounting for variations in rest periods, charge-discharge rates, and temperatures. We also detail procedures for validating tests experimentally within a climate-controlled chamber and for developing an empirical model to estimate capacity fading under various testing objectives. For complete details on the use and execution of this protocol, please refer to Mulpuri et al.1.
A firm link between endoplasmic reticulum (ER) stress and tumors has been wildly reported. Endoplasmic reticulum oxidoreductase 1 alpha (ERO1α), an ER-resident thiol oxidoreductase, is confirmed to be highly upregulated in various cancer types and associated with a significantly worse prognosis. Of importance, under ER stress, the functional interplay of ERO1α/PDI axis plays a pivotal role to orchestrate proper protein folding and other key processes. Multiple lines of evidence propose ERO1α as an attractive potential target for cancer treatment. However, the unavailability of specific inhibitor for ERO1α, its molecular inter-relatedness with closely related paralog ERO1β and the tightly regulated processes with other members of flavoenzyme family of enzymes, raises several concerns about its clinical translation. Herein, we have provided a detailed description of ERO1α in human cancers and its vulnerability towards the aforementioned concerns. Besides, we have discussed a few key considerations that may improve our understanding about ERO1α in tumors.
Accurate global horizontal irradiance (GHI) forecasting is critical for integrating solar energy into the power grid and operating solar power plants. The Weather Research and Forecasting model with its solar radiation extension (WRF-Solar) has been used to forecast solar irradiance in different regions around the world. However, the application of the WRF-Solar model to the prediction of GHI in West Africa, particularly Ghana, has not yet been investigated. The aim of this study is to evaluate the performance of the WRF-Solar model for predicting GHI in Ghana, focusing on three automatic weather stations (Akwatia, Kumasi and Kologo) for the year 2021. We used two one-way nested domains (D1 = 15 km and D2 = 3 km) to investigate the ability of the fully coupled WRF-Solar model to forecast GHI up to 72-hour ahead under different atmospheric conditions. The initial and lateral boundary conditions were taken from the ECMWF high-resolution operational forecasts. Our findings reveal that the WRF-Solar model performs better under clear skies than cloudy skies. Under clear skies, Kologo performed best in predicting 72-hour GHI, with a first day nRMSE of 9.62 %. However, forecasting GHI under cloudy skies at all three sites had significant uncertainties. Additionally, WRF-Solar model is able to reproduce the observed GHI diurnal cycle under high AOD conditions in most of the selected days. This study enhances the understanding of the WRF-Solar model’s capabilities and limitations for GHI forecasting in West Africa, particularly in Ghana. The findings provide valuable information for stakeholders involved in solar energy generation and grid integration towards optimized management in the region.
Green infrastructure has been widely recognized for the benefits to human health and biodiversity conservation. However, knowledge of the qualities and requirements of such spaces and structures for the effective delivery of the range of ecosystem services expected is still limited, as well as the identification of trade-offs between services. In this study, we apply the One Health approach in the context of green spaces to investigate how urban park characteristics affect human mental health and wildlife support outcomes and identify synergies and trade-offs between these dimensions. Here we show that perceived restorativeness of park users varies significantly across sites and is mainly affected by safety and naturalness perceptions. In turn, these perceptions are driven by objective indicators of quality, such as maintenance of facilities and vegetation structure, and subjective estimations of biodiversity levels. The presence of water bodies benefited both mental health and wildlife. However, high tree canopy coverage provided greater restoration potential whereas a certain level of habitat heterogeneity was important to support a wider range of bird species requirements. To reconcile human and wildlife needs in green spaces, cities should strategically implement a heterogeneous green infrastructure network that considers trade-offs and maximizes synergies between these dimensions.
Pipeline transport is an efficient method for transporting fluids in energy supply and other technical applications. While natural gas is the classical example, the transport of hydrogen is becoming more and more important; both are transmitted under high pressure in a gaseous state. Also relevant is the transport of carbon dioxide, captured in the places of formation, transferred under high pressure in a liquid or supercritical state and pumped into underground reservoirs for storage. The transport of other fluids is also required in technical applications. Meanwhile, the transport equations for different fluids are essentially the same, and the simulation can be performed using the same methods. In this paper, the effect of control elements such as compressors, regulators and flaptraps on the stability of fluid transport simulations is studied. It is shown that modeling of these elements can lead to instabilities, both in stationary and dynamic simulations. Special regularization methods were developed to overcome these problems. Their functionality also for dynamic simulations is demonstrated for a number of numerical experiments.
Farming communities confronted with climate change adopt formal and informal adaptation strategies to mitigate the effects of climate change. While the environmental and social effects of climate change are well documented, there is still a dearth of literature on girl-child marriage (formal marriage or informal union between a child under the age of 18 and an adult or another child) as a response to the effects of climate change. In this research, we ask if girl-child marriage is promoted as a social protection mechanism first, rather than as simply a response to climate-induced poverty. We use qualitative semi-structured interviews and focus group discussions to explore this question in a rural farming community in Northern Ghana. Our findings reveal that climate change shocks result in poverty and compel farmers to marry off their young daughters. The unmarried girl-child is perceived as an ‘extra mouth to feed’, a liability whose marriage becomes a strategy for protecting the family, the family’s reputation, and the girl child. The emphasis in girl-child marriage is not on the girl-child as an individual but on the family as a group. Hence, what is good for the family is assumed to be in the best interest of the girl-child. We place our analysis at the intersection of climate change, social protection, and the incidence of girl-child marriages. We argue that understanding this link is crucial and can contribute significantly to our knowledge of girl-child marriage as well as our ability to address this in Sub-Saharan Africa.
The transport sector is a major source of air pollution and thus a major contributor to the changing climate. As a result, in the recent past, driving bans have been imposed on cars with critical pollutant groups. As an international UN campus and self-proclaimed climate capital, the Federal City of Bonn declared a climate emergency in 2019 and participated in a federally funded “Lead City” project to optimise air quality. A key goal of the project is to reduce private motorised transport and strengthen public transport. Among the implemented measures, a “climate ticket” was introduced in 2019 whereby consumers could purchase an annual 365 € ticket for all local public transport. This paper reports on an analysis of that ticket’s changes in travel behavior.
A quantitative survey (n = 1,315) of the climate ticket users as well as the multiple regressions confirm that the climate ticket attracted more customers to the buses and trams and that a modal shift for the period of the measure was recognisable. The multiple regressions showed that the ticket was perceived significantly more positively by full-time employed users than by unemployed people. The results also show that, in addition to the price, it is essential that travel time and reliability are ensured. Furthermore, the eligible groups of people, the area of coverage, and good connecting services should be extended. To sustainably improve air quality, this type of mobility service must be optimised and introduced on a permanent basis.
The human gut microbiota harbors untapped potential for biotechnological applications. Within the phylum of Bacteroidota, Phocaeicola vulgatus stands out as a promising candidate for sustainable production of key platform chemicals like succinate. However, genetic engineering of Phocaeicola sp. remains challenging due to its intricate molecular landscape. This study lays the groundwork for manipulating the central carbon pathways in Phocaeicola vulgatus, offering insights into overcoming genetic hurdles for increased succinate yields.
Improved Thermal Comfort Model Leveraging Conditional Tabular GAN Focusing on Feature Selection
(2024)
The indoor thermal comfort in both homes and workplaces significantly influences the health and productivity of inhabitants. The heating system, controlled by Artificial Intelligence (AI), can automatically calibrate the indoor thermal condition by analyzing various physiological and environmental variables. To ensure a comfortable indoor environment, smart home systems can adjust parameters related to thermal comfort based on accurate predictions of inhabitants’ preferences. Modeling personal thermal comfort preferences poses two significant challenges: the inadequacy of data and its high dimensionality. An adequate amount of data is a prerequisite for training efficient machine learning (ML) models. Additionally, high-dimensional data tends to contain multiple irrelevant and noisy features, which might hinder ML models’ performance. To address these challenges, we propose a framework for predicting personal thermal comfort preferences, combining the conditional tabular generative adversarial network (CTGAN) with multiple feature selection techniques. We first address the data inadequacy challenge by applying CTGAN to generate synthetic data samples, incorporating challenges associated with multimodal distributions and categorical features. Then, multiple feature selection techniques are employed to identify the best possible sets of features. Experimental results based on a wide range of settings on a standard dataset demonstrated state-of-the-art performance in predicting personal thermal comfort preferences. The results also indicated that ML models trained on synthetic data achieved significantly better performance than models trained on real data. Overall, our method, combining CTGAN and feature selection techniques, outperformed existing known related work in thermal comfort prediction in terms of multiple evaluation metrics, including area under the curve (AUC), Cohen’s Kappa, and accuracy. Additionally, we presented a global, model-agnostic explanation of the thermal preference prediction system, providing an avenue for thermal comfort experiment designers to consciously select the data to be collected.
Trade of wild-caught animals is illegal for many taxa and in many countries. Common regulatory procedures involve documentation and marking techniques. However, these procedures are subject to fraud and thus should be complemented by routine genetic testing in order to authenticate the captive-bred origin of animals intended for trade. A suitable class of genetic markers are SNPSTRs that combine a short tandem repeat (STR) and single nucleotide polymorphisms (SNPs) within one amplicon. This combined marker type can be used for genetic identification and for parentage analyses and in addition, provides insight into haplotype history. As a proof of principle, this study establishes a set of 20 SNPSTR markers for Athene noctua, one of the most trafficked owls in CITES Appendix II. These markers can be coamplified in a single multiplex reaction. Based on population data, the percentage of observed and expected heterozygosities of the markers ranged from 0.400 to 1.000 and 0.545 to 0.850, respectively. A combined probability of identity of 5.3*10-23 was achieved with the whole set, and combined parentage exclusion probabilities reached over 99.99%, even if the genotype of one parent was missing. A direct comparison of an owl family and an unrelated owl demonstrated the applicability of the SNPSTR set in parentage testing. The established SNPSTR set thus proved to be highly useful for identifying individuals and analysing parentage to determine wild or captive origin. We propose to implement SNPSTR-based routine certification in wildlife trade as a way to reveal animal laundering and misdeclaration of wild-caught animals.
The lattice Boltzmann method (LBM) stands apart from conventional macroscopic approaches due to its low numerical dissipation and reduced computational cost, attributed to a simple streaming and local collision step. While this property makes the method particularly attractive for applications such as direct noise computation, it also renders the method highly susceptible to instabilities. A vast body of literature exists on stability-enhancing techniques, which can be categorized into selective filtering, regularized LBM, and multi-relaxation time (MRT) models. Although each technique bolsters stability by adding numerical dissipation, they act on different modes. Consequently, there is not a universal scheme optimally suited for a wide range of different flows. The reason for this lies in the static nature of these methods; they cannot adapt to local or global flow features. Still, adaptive filtering using a shear sensor constitutes an exception to this. For this reason, we developed a novel collision operator that uses space- and time-variant collision rates associated with the bulk viscosity. These rates are optimized by a physically informed neural net. In this study, the training data consists of a time series of different instances of a 2D barotropic vortex solution, obtained from a high-order Navier–Stokes solver that embodies desirable numerical features. For this specific text case our results demonstrate that the relaxation times adapt to the local flow and show a dependence on the velocity field. Furthermore, the novel collision operator demonstrates a better stability-to-precision ratio and outperforms conventional techniques that use an empirical constant for the bulk viscosity.
This article deals with the under-researched phenomenon of rural health entrepreneurship and its major characteristics. The purpose of this study is to explicate the process of providing health services in rural areas of a developing country and their relation to SDGs. The paper is based on six semi-structured interviews conducted with Serbian health entrepreneurs in rural areas (two private practices, two policlinics, and two dental practices), a review of laws and strategies relevant to the field, and three sessions of discussions with eight experts (four authors and four additional experts). The research methodology follows an empirical, mixed-method case study research procedure. The results are presented in relation to the aspects of frugality, family orientation, and sustainability-oriented innovation. The timeline of the six case studies demonstrates the increasing importance of health entrepreneurs in rural areas due to the aging population and, therefore, increased needs for quality healthcare in these areas. The financing instruments have also become more formal and substantial in recent years, enabling the growth of healthcare businesses in rural areas. However, a major obstacle to further sustainable development remains the non-refundability of services before the state-owned, obligatory health fund, creating major social inequalities, especially in rural areas.
In addition to the long-term goal of mitigating climate change, the current geopolitical upheavals heighten the urgency to transform Europe's energy system. This involves expanding renewable energies while managing intermittent electricity generation. Hydrogen is a promising solution to balance generation and demand, simultaneously decarbonizing complex applications. To model the energy system's transformation, the project TransHyDE-Sys, funded by the German Federal Ministry of Education and Research, takes an integrated approach beyond traditional energy system analysis, incorporating a diverse range of more detailed methods and tools. Herein, TransHyDE-Sys is situated within the recent policy discussion. It addresses the requirements for energy system modeling to gain insights into transforming the European hydrogen and energy infrastructure. It identifies knowledge gaps in the existing literature on hydrogen infrastructure-oriented energy system modeling and presents the research approach of TransHyDE-Sys. TransHyDE-Sys analyzes the development of hydrogen and energy infrastructures from “the system” and “the stakeholder” perspectives. The integrated modeling landscape captures temporal and spatial interactions among hydrogen, electricity, and natural gas infrastructure, providing comprehensive insights for systemic infrastructure planning. This allows a more accurate representation of the energy system's dynamics and aids in decision-making for achieving sustainable and efficient hydrogen network development integration.
Interne Audits können mehr
(2024)
Dieser Beitrag zeigt, wie das Deutsche Zentrum für Luft- und Raumfahrt e. V. (DLR) Zufriedenheitsanalysen aus zwei Sichtweisen durchführt: Aus Sicht der Auditoren und aus Sicht der Managementbeauftragten der auditierten Institute und Einrichtungen. Die Ergebnisse fließen in die jährliche Auditprogrammplanung ein. Damit wird der Nutzen von internen Audits gesteigert.
Introduction: The paper analyses – basing itself on reports and other documents created by different parts of the International Labour Organisation (ILO) – the process which led to the adoption of Social Protection Floor Recommendation No. 202 and the shift in focus of social policy advice towards basic protection and to the Global South countries. We look at the actions of different actors which shape the standard setting and policy stand of the organisation. Objective: To provide a comprehensive analysis of the historical trajectory of ILO social security standards, examining the evolution of principles, conventions, and the global dynamics that have shaped the organization's approach to social protection over time. Materials and methods: The methods include examining ILO documents, relevant subject literature, and the author's participant observations from over twenty-years of service in the ILO's Social Security Department, aiming to provide insights into the decision-making processes within the organization. Conclusion: We conclude that change was brought by: 1) shift in the membership of the ILO and of its decision-making bodies towards the increased presence and powers of representatives from countries of the Global South, 2) the shift in the global development community policy priorities towards poverty reduction, 3) emergence of experimental social assistance schemes in Global South countries, with designs often ignoring principles embedded in the ILO standards. The Social Protection Floor Recommendation complements previous standards in response to the challenges of widespread poverty and informality and spreading atypical forms of employment. It provides two directions of policy responses: 1) formalizing informal employment relationships and 2) expanding universal or targeted rights-based social assistance schemes. Assistance provided by ILO to member states focuses now more on building the non-contributory schemes and on identifying the fiscal space necessary to close the coverage gaps. Nowadays, the ILO must collaborate more than before with other development partners and the main challenge is to build among them awareness and acceptance of the principles of the ILO social security standards.
There are several recent works which had proposed an automatic computer-aided diagnosis (CAD) deep learning (DL) model to diagnose coronavirus disease 2019 (COVID-19) using chest x-ray images (CXR) to propose a high-accuracy CAD method to detect COVID-19 automatically. In this study, seven different models including Convolutional Neural Network (CNN) models such as VGG-16 and vision transformer (ViT) models, are proposed. The different proposed models are trained with a three-class balanced dataset consisting of 3,000 CXR images consisting of 1,000 CXR images for each class of COVID-19, Normal, and Lung-Opacity. A publicly available dataset to train and test the models is used from Kaggle-COVID-19-Radiography-Dataset. From the experiments, the accuracy of the VGG16 model is 93.44% and ViT's is 92.33%. Besides, the binary classification between two classes of COVID-19 and Normal CXR with a limited number of just 100 images for each class, using a transfer learning technique, with a validation accuracy of 97.5% is proposed.
This work proposes a novel approach for probabilistic end-to-end all-sky imager-based nowcasting with horizons of up to 30 min using an ImageNet pre-trained deep neural network. The method involves a two-stage approach. First, a backbone model is trained to estimate the irradiance from all-sky imager (ASI) images. The model is then extended and retrained on image and parameter sequences for forecasting. An open access data set is used for training and evaluation. We investigated the impact of simultaneously considering global horizontal (GHI), direct normal (DNI), and diffuse horizontal irradiance (DHI) on training time and forecast performance as well as the effect of adding parameters describing the irradiance variability proposed in the literature. The backbone model estimates current GHI with an RMSE and MAE of 58.06 and 29.33 W m−2, respectively. When extended for forecasting, the model achieves an overall positive skill score reaching 18.6 % compared to a smart persistence forecast. Minor modifications to the deterministic backbone and forecasting models enables the architecture to output an asymmetrical probability distribution and reduces training time while leading to similar errors for the backbone models. Investigating the impact of variability parameters shows that they reduce training time but have no significant impact on the GHI forecasting performance for both deterministic and probabilistic forecasting while simultaneously forecasting GHI, DNI, and DHI reduces the forecast performance.
Integrating physical simulation data into data ecosystems challenges the compatibility and interoperability of data management tools. Semantic web technologies and relational databases mostly use other data types, such as measurement or manufacturing design data. Standardizing simulation data storage and harmonizing the data structures with other domains is still a challenge, as current standards such as the ISO standard STEP (ISO 10303 ”Standard for the Exchange of Product model data”) fail to bridge the gap between design and simulation data. This challenge requires new methods, such as ontologies, to rethink simulation results integration. This research describes a new software architecture and application methodology based on the industrial standard ”Virtual Material Modelling in Manufacturing” (VMAP). The architecture integrates large quantities of structured simulation data and their analyses into a semantic data structure. It is capable of providing data permeability from the global digital twin level to the detailed numerical values of data entries and even new key indicators in a three-step approach: It represents a file as an instance in a knowledge graph, queries the file’s metadata, and finds a semantically represented process that enables new metadata to be created and instantiated.