Critical Process Research Articles

Energy Efficient for Heat Exchanger Refrigeration and Air Conditioning

Scientifically, it is difficult to predict the relationship between global temperature and greenhouse gas (GHG) concentrations. The climate system contains many processes that will change if warming occurs. Critical processes include heat transfer by winds and tides, the hydrological cycle involving evaporation, precipitation, runoff and groundwater and the formation of clouds, snow, and ice, all of which display enormous natural variability. The equipment and infrastructure for energy supply and use are designed with long lifetimes, and the premature turnover of capital stock involves significant costs. Economic benefits occur if capital stock is replaced with more efficient equipment in step with its normal replacement cycle. Likewise, if opportunities to reduce future emissions are taken in a timely manner, they should be less costly.

Language portraits going digital and multimodal: deciphering the translanguaging space and linguistic repertoires among multilinguals

In recent years, language portraits (LPs) have emerged as a valuable tool for visually representing multilingual learners’ linguistic repertoires. However, previous studies have primarily relied on traditional methods of inviting participants to sketch their language portraits on paper using pens and crayons. In this paper, we propose the use of digital methods to collect and analyze data on language portraits to examine the translingual practices and negotiations of meaning among multilingual individuals. By utilizing Synchronic Computer-Mediated Communication platforms, participants can actively deploy and mobilize multi-linguistic and multi-semiotic resources in lived experiences, engaging in interactive translanguaging practices. In this particular case study, data were collected through a biographic survey and a sketch of the language portraits in digital form, which were then further supported by follow-up interviews. Four participants’ LPs and oral narratives during the interviews were then subjected to qualitative multimodal analysis and discourse analysis. The results revealed that these digital language portraits (DLPs) possess significant features such as digital affordance and multimodality. They tap into the translanguaging spaces that emerge from the creative and critical meaning-making process, enabling multilingual individuals to visualize their linguistic repertoires through digital visual strategies. Furthermore, it was discovered that DLPs can foster creative performance and discursive negotiations, thereby enhancing participants’ expressive abilities in developing their language perceptions.

Errors in memory recall, ToT, SoT, FoK and BoP. Operational classification

The evocation of memory is a critical cognitive process that involves the activation of engrams, which in turn evoke concepts. During memory recall, errors often occur, some of which are well-known, such as the tip-of-the-tongue (ToT) phenomenon or slip of the tongue (SoT). A related variable is verbal taxonomy closely associated with ToT and SoT, as well as the anxiety variable, which has been linked to the occurrence of these phenomena. The results of this research identify errors unrelated to verbs, leading to the operationalization of previously unidentified phenomena called Bias of Perception (BoP) and feeling of Knowing (FoK). This paper explores these errors and their systematic occurrence. In summary, this document seeks to increase understanding of errors that occur during memory recall, their causes, and their implications for cognitive processes.

Laser marking on polyoxymethylene (POM) polymer substrate for a lean manufacturing application

AbstractLaser marking is a critical production process step in most automated production systems. However, some materials such as polyoxymethylene (POM) can be quite challenging to laser to 80 kHz.mark, hence the need to develop new laser marking methods. By employing a wide range of marking parameters (marking speed 15–2000 mm/s, laser power from 10 to 100% of 30 W maximum, and frequencies mainly from 1 to 400 kHz) and characterization techniques, and with the use of marker inks as masking agents successful laser marking POM is demonstrated irrespective of its presentation (white or black coloured) using a new method akin to Laser Polymer Tattooing (LPT), and without prior modification of polymer composition (by addition of laser marking additives). Results indicate laser marking of acceptable quality can be obtained with black POM at marking speeds up to 2000 mm/s. For white POM, markings of acceptable quality were obtained at markings speeds up to 100 mm/s, with laser power ≥ 80% (of 30 W maximum), and with frequencies in the range of 20 kHz with the help of a masking agent. The effects of the laser marking parameters on marking quality and the changes induced in the material are presented and discussed. The wide range of marking parameters employed enabled the determination of feasible marking parameters for the development of a lean manufacturing-based automatic and self-evaluating and improving laser marking system with minimal human intervention.

Dynamic N6 -methyladenosine RNA modification regulates peanut resistance to bacterial wilt.

N6 -methyladenosine (m6 A) is the most abundant mRNA modification in eukaryotes and is an important regulator of gene expression as well as many other critical biological processes. However, the characteristics and functions of m6 A in peanut (Arachis hypogea L.) resistance to bacterial wilt (BW) remain unknown. Here, we analyzed the dynamic of m6 A during infection of resistant (H108) and susceptible (H107) peanut accessions with Ralstonia solanacearum (R. solanacearum), the causative agent of BW. Throughout the transcriptome, we identified 'URUAY' as a highly conserved motif for m6 A in peanut. The majority of differential m6 A located within the 3' untranslated region (UTR) of the transcript, with fewer in the exons. Integrative analysis of RNA-Seq and m6 A methylomes suggests the correlation between m6 A and gene expression in peanut R. solanacearum infection, and functional analysis reveals that m6 A-associated genes were related to plant-pathogen interaction. Our experimental analysis suggests that AhALKBH15 is an m6 A demethylase in peanut, leading to decreased m6 A levels and upregulation of the resistance gene AhCQ2G6Y. The upregulation of AhCQ2G6Y expression appears to promote BW resistance in the H108 accession.

Enhancing the borosilicate glass micromachining by using mixed alkaline electrolytes in the ECDM process

ABSTRACT This article investigates the effects of mixing different alkaline electrolytes on the geometrical features created by the ECDM. Sodium hydroxide (NaOH) and potassium hydroxide (KOH) were mixed in varying volumetric proportions. Effect of critical process parameters on the depth and width of the microchannels and the associated tool wear was investigated. Pure NaOH electrolyte has resulted in the highest depth compared to the pure KOH electrolyte. Process mechanism behind the role of mixed electrolytes on the opening sizes and depths of microchannels is explained. Higher material removal by the NaOH electrolyte was due to the larger number of sodium (Na+) ions in the electrolyte, resulting in more aggressive electrochemical discharge; however, it also resulted in severe tool wear. Mixed electrolytes with a KOH yielded lower width and low tool wear. Increasing the volumetric proportion of KOH in the mixed electrolyte gradually decreased the machining depth, width, and tool wear.

Quality Tolerance Limits: A General Guidance for Parameter Selection and Threshold Setting.

The past years have sharpened the industry's understanding of a Quality by Design (QbD) approach toward clinical trials. Using QbD encourages designing quality into a trial during the planning phase. The identification of Critical to Quality (CtQs) factors and specifically Critical Data and Processes (CD&Ps) is key to such a risk-based monitoring approach. A variable that allows monitoring the evolution of risk regarding the CD&Ps is called a Quality Tolerance Limit (QTL) parameter. These parameters are linked to the scientific question(s) of a trial and may identify the issues that can jeopardize the integrity of trial endpoints. This paper focuses on defining what QTL parameters are and providing general guidance on setting thresholds for these parameters allowing for the derivation of an acceptable range of the risk.

Protein succinylation: regulating metabolism and beyond.

Modifications of protein post-translation are critical modulatory processes, which alters target protein biological activity，function and/or location, even involved in pathogenesis of some diseases. So far, there are at least 16 types of post-translation modifications identified, particularly through recent mass spectrometry analysis. Among them, succinylation (Ksuc) on protein lysine residues causes a variety of biological changes. Succinylation of proteins contributes to many cellular processes such as proliferation, growth, differentiation, metabolism and even tumorigenesis. Mechanically, Succinylation leads to conformation alteration of chromatin or remodeling. As a result, transcription/expression of target genes is changed accordingly. Recent research indicated that succinylation mainly contributes to metabolism modulations, from gene expression of metabolic enzymes to their activity modulation. In this review, we will conclude roles of succinylation in metabolic regulation of glucose, fat, amino acids and related metabolic disease launched by aberrant succinylation. Our goal is to stimulate extra attention to these still not well researched perhaps important succinylation modification on proteins and cell processes.

Gate-controlled gain tuning of fully depleted silicon-on-insulator-based 1 T pixel for in-sensor white balance

White balance (WB) is a critical back-end processing function in image sensors to keep color constancy under various lighting conditions by adjusting the RGB color channel gain values. In this work, we proposed a novel gate-controlled gain-tuning method for a fully depleted silicon-on-insulator (FDSOI) one-transistor (1 T) pixel to achieve WB inside the sensor. Based on the pixel structure of a p-well under the buried oxide for sensing and an n-type nMOSFET on the top for readout, the 1 T pixel output gain is modulated by the MOSFET gate according to the transistor transfer characteristics. About 5x gain modulation range in RGB spectrum photoresponse (nonlinearity < 3%) is experimentally demonstrated in the devices fabricated by 22 nm FDSOI-based technology. The scheme for in-sensor WB demonstration is provided with a novel 1 T pixel array design, and the evaluation result shows in-sensor WB achieving an almost equivalent performance (Delta-E deviation < 1) compared with using conventional back-end WB.

The assessment of the mechanism of action of lauric acid in the context of oral cancer through integrative approach combining network pharmacology and molecular docking technology.

Lauric acid has been investigated for its effects on various human cancer cell types, although limited research has been dedicated to its impact on oral cancer. In light of this, the objective of our study was to comprehensively assess the anticancer properties of lauric acid specifically in the context of oral cancer. This evaluation was achieved through an in-silico approach, leveraging network analysis techniques. By employing this methodology, we aimed to gain valuable insights into the potential therapeutic benefits of lauric acid for treating oral cancer. The in-silico analysis involved determination of drug-likeness prediction, prediction of common targets between oral cancer and LA, protein-protein interactions (PPI), hub genes, top 10 associated pathways by gene ontology (GO), Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway, molecular docking experiments. Our study pinpointed 23 common genes involved in critical cellular processes, including proliferation, apoptosis regulation, PI3K AKT cascade, and cell cycle control. Among them, CXCL8, MMP9, PPARA, MAPK1, and AR stood out in the top 10 pathways, particularly in the PI3K/AKT signaling pathway. This highlights the potential role of lauric acid in oral cancer treatment through the PI3K/AKT pathway and calls for further exploration of this mechanism. Our study highlights lauric acid's promising anticancer properties through computational analysis, offering a foundation for future research in cancer treatment development. This approach combines molecular insights with in-silico methods, paving the way for identifying therapeutic compounds and understanding their mechanisms. Lauric acid holds potential as a chemotherapeutic agent, opening up new avenues for cancer therapy exploration.

Surface roughness analysis of Cu seed layer deposited on α-Ti diffusion barrier layer: A molecular dynamics simulation study

Copper (Cu) interconnections have been widely used in advanced electronic packaging due to their outstanding thermal and electric properties. Preparing a smooth and uniform Cu seed thin layer is one of the critical processes to obtain high-reliability Cu interconnections. The barrier layer between Cu and silicon (Si) devices is necessary to prevent the inter-diffusion between Cu and Si. However, little work has been done on the surface roughness analysis of the Cu seed layer deposited on the diffusion barrier layer. In this paper, the influences of deposition thickness, incident energy, barrier layer temperature, and surface morphology on the surface roughness of the Cu seed layer deposited on α-titanium (α-Ti) barrier layer were studied in detail by the molecular dynamics (MD). The simulation results indicated that appropriate parameters have a beneficial effect on reducing the surface roughness, and the surface morphology of the Cu seed layer strongly connects with that of the barrier layer. These results provided a foundation for optimizing the quality of the Cu seed layer.

Milli Eğitim Yönetiminde Eğitim Politikası Analiz Sürecini Uygulamaya Dönüştürme

Summary Limitations on developing real knowledge about the education system and its performance minimize the lack of potential resources in policy development. This type of information also forms the basis for achieving consensus. Understanding the problems in the education system, developing the sharing and finding a strategy for it is a critical process in reaching the foundation. Because such consensus is a key to encouraging synergetic action and cooperation by many segments that typically play a role in parts of implementation policies in the education system. To illustrate the difficulty of achieving consensus in the absence of good analytical work, we have to say that it is the best in policy discussions with priority views on the weaknesses and strengths of the education system, and how its performance should best be improved. As a result, it is not a surprise to see the political discussions at an impasse. Because it is difficult to assess the pros and cons of options only on the basis of theoretical arguments. For example, someone might argue that multilevel learning is pedagogically weak. But someone else also claims that equal-level learning can be quite effective. Because in this, each student devotes more time independently and makes the demands on teachers to teach the diversity of students' learning styles more obvious. It is not possible to emphasize the validity of any assessment of the effectiveness of multiple learning without empirical evidence to compare learning outcomes under the alternative learning arrangement. Of course, analytical work does not consist of discussion alone. But it helps those who shed light on the thoughts in reaching that conclusion. Key Words: National Education, Education Management, Education Policy, Analysis Process

AgroTech advancing agriculture through innovative design and development of solar-powered seed sowing, fertilizer dispensing, precision water sprinkling, and chemical fertilizer sprinkling machine

This research explores the intersection of technology and agriculture, focusing on the design and development of solar-powered machines that are set to revolutionize farming. The study examines the use of solar energy in critical agricultural processes like seed sowing, fertilizer dispensing, precision water sprinkling, and chemical fertilizer application. The goal is to improve operational efficiency, reduce environmental impact, and promote sustainable farming practices. To achieve this goal, the research evaluates the technical intricacies of solar-powered machinery and their reliability and adaptability across diverse agricultural contexts. The financial viability and potential advantages for farmers are also analyzed through a detailed cost-benefit analysis. The importance of solar- powered AgroTech in mitigating carbon footprints, promoting eco-friendly farming practices, and contributing to overall environmental sustainability is emphasized. In addition, the study highlights the precision capabilities of these machines and their role in optimizing seed placement, judicious fertilizer application, and efficient water management. By providing a comprehensive understanding of how solar-powered AgroTech can catalyse sustainable agriculture, this research offers valuable insights for farmers, policymakers, and industry stakeholders navigating the evolving landscape of modern farming.

Proteomics revealed composition- and size-related regulators for hepatic impairments induced by silica nanoparticles

Along with the growing production and application of silica nanoparticles (SiNPs), increased human exposure and ensuing safety evaluation have progressively attracted concern. Accumulative data evidenced the hepatic injuries upon SiNPs inhalation. Still, the understanding of the hepatic outcomes resulting from SiNPs exposure, and underlying mechanisms are incompletely elucidated. Here, SiNPs of two sizes (60 nm and 300 nm) were applied to investigate their composition- and size-related impacts on livers of ApoE−/− mice via intratracheal instillation. Histopathological and biochemical analysis indicated SiNPs promoted inflammation, lipid deposition and fibrosis in the hepatic tissue, accompanied by increased ALT, AST, TC and TG. Oxidative stress was activated upon SiNPs stimuli, as evidenced by the increased hepatic ROS, MDA and declined GSH/GSSG. Of note, these alterations were more dramatic in SiNPs with a smaller size (SiNPs-60) but the same dosage. LC-MS/MS-based quantitative proteomics unveiled changes in mice liver protein profiles, and filtered out particle composition- or size-related molecules. Interestingly, altered lipid metabolism and oxidative damage served as two critical biological processes. In accordance with correlation analysis and liver disease-targeting prediction, a final of 10 differentially expressed proteins (DEPs) were selected as key potential targets attributable to composition- (4 molecules) and size-related (6 molecules) liver impairments upon SiNPs stimuli. Overall, our study provided strong laboratory evidence for a comprehensive understanding of the harmful biological effects of SiNPs, which was crucial for toxicological evaluation to ensure nanosafety.

Hepatitis B virus RNAs co-opt ELAVL1 for stabilization and CRM1-dependent nuclear export.

Hepatitis B virus (HBV) chronically infects 296 million people worldwide, posing a major global health threat. Export of HBV RNAs from the nucleus to the cytoplasm is indispensable for viral protein translation and genome replication, however the mechanisms regulating this critical process remain largely elusive. Here, we identify a key host factor embryonic lethal, abnormal vision, Drosophila-like 1 (ELAVL1) that binds HBV RNAs and controls their nuclear export. Using an unbiased quantitative proteomics screen, we demonstrate direct binding of ELAVL1 to the HBV pregenomic RNA (pgRNA). ELAVL1 knockdown inhibits HBV RNAs posttranscriptional regulation and suppresses viral replication. Further mechanistic studies reveal ELAVL1 recruits the nuclear export receptor CRM1 through ANP32A and ANP32B to transport HBV RNAs to the cytoplasm via specific AU-rich elements, which can be targeted by a compound CMLD-2. Moreover, ELAVL1 protects HBV RNAs from DIS3+RRP6+ RNA exosome mediated nuclear RNA degradation. Notably, we find HBV core protein is dispensable for HBV RNA-CRM1 interaction and nuclear export. Our results unveil ELAVL1 as a crucial host factor that regulates HBV RNAs stability and trafficking. By orchestrating viral RNA nuclear export, ELAVL1 is indispensable for the HBV life cycle. Our study highlights a virus-host interaction that may be exploited as a new therapeutic target against chronic hepatitis B.

Enhancing Control Room Operator Decision Making

In the dynamic and complex environment of industrial control rooms, operators are often inundated with numerous tasks and alerts, leading to a state known as task overload. This condition can result in decision fatigue and increased reliance on cognitive biases, which may compromise the decision-making process. To mitigate these risks, the implementation of decision support systems (DSSs) is essential. These systems are designed to aid operators in making swift, well-informed decisions, especially when their judgment may be faltering. Our research presents an artificial intelligence (AI)-based framework utilizing dynamic influence diagrams and reinforcement learning to develop a powerful decision support system. The foundation of this AI framework is the creation of a robust, interpretable, and effective DSS that aids control room operators during critical process disturbances. By incorporating expert knowledge, the dynamic influence diagram provides a comprehensive model that captures the uncertainties inherent in complex industrial processes. It excels in anomaly detection and recommending optimal actions. Furthermore, this model is improved through a strategic collaboration with reinforcement learning, which refines the recommendations to be more context-specific and accurate. The primary goal of this AI framework is to equip operators with a live, reliable DSS that significantly enhances their response during process upsets. This paper describes the development of the AI framework and its implementation in a simulated control room environment. Our results show that the DSS can improve operator performance and reduce cognitive workload. However, it also uncovers a trade-off with situation awareness, which may decrease as operators become overly dependent on the system’s guidance. Our study highlights the necessity of balancing the advantages of decision support with the need to maintain operator engagement and understanding during process operations.

ERORUN‐STAFOR: A collaborative observatory for the multidisciplinary study of the critical zone processes in a tropical volcanic watershed including a Tropical Montane Cloud Forest

AbstractTropical volcanic islands are biodiversity hotspots where the Critical Zone (CZ) still remains poorly studied. In such steep topographic environments associated with extreme climatic events (cyclones), deployment and maintenance of monitoring equipment is highly challenging. While a few Critical Zone Observatories (CZOS) are located in tropical volcanic regions, none of them includes a Tropical Montane Cloud Forest (TMCF) at the watershed scale. We present here the dataset of the first observatory from the French network of critical zone observatories (OZCAR) located in an insular tropical and volcanic context, integrating a ‘Tropical Montane Cloud Forest’: The ERORUN‐STAFOR observatory. This collaborative observatory is located in the northern part of La Réunion island (Indian Ocean) within the 45.0 km2 watershed of Rivière des Pluies (i.e., Rainfall river) which hosts the TMCF of Plaines des Fougères, one of the best preserved natural habitats in La Réunion Island. Since 2014, the ERORUN‐STAFOR monitoring in collaboration with local partners collected a multidisciplinary dataset with a constant improvement of the instrumentation over time. At the watershed scale and in its vicinity, the ERORUN‐STAFOR observatory includes 10 measurement stations covering the upstream, midstream and downstream part of the watershed. The stations record a total of 48 different variables through continuous (sensors) or periodic (sampling) monitoring. The dataset consists of continuous time series variables related to (i) meteorology, including precipitation, air temperature, relative humidity, wind speed and direction, net radiation, atmospheric pressure, cloud water flux, irradiance, leaf wetness and soil temperature, (ii) hydrology, including water level and temperature, discharge and electrical conductivity (EC) of stream, (iii) hydrogeology, including (ground)water level, water temperature and EC in two piezometers and one horizontally drilled groundwater gallery completed by soil moisture measurements under the canopy. The dataset is completed by periodic time series variables related to (iv) hydrogeochemistry, including field parameters and water analysis results. The periodic sampling survey provides chemical and isotopic compositions of rainfall, groundwater, and stream water at different locations of this watershed. The ERORUN‐STAFOR monitoring dataset extends from 2014 to 2022 with an acquisition frequency from 10 min to hourly for the sensor variables and from weekly to monthly frequency for the sampling. Despite the frequent maintenance of the monitoring sites, several data gaps exist due to the remote location of some sites and instrument destruction by cyclones. Preliminary results show that the Rivière des Pluies watershed is characterized by high annual precipitation (&gt;3000 mm y−1) and a fast hydrologic response to precipitation (≈2 h basin lag time). The long‐term evolution of the deep groundwater recharge is mainly driven by the occurrence of cyclone events with a seasonal groundwater response. The water chemical results support existing hydrogeological conceptual models suggesting a deep infiltration of the upstream infiltrated rainfall. The TMCF of Plaine des Fougères shows a high water storage capacity (&gt;2000% for the Bryophytes) that makes this one a significant input of water to groundwater recharge which still needs to be quantified. This observatory is a unique research site in an insular volcanic tropical environment offering three windows of observation for the study of critical zone processes through upstream‐midstream‐downstream measurements sites. This high‐resolution dataset is valuable to assess the response of volcanic tropical watersheds and aquifers at both event and long‐term scales (i.e., global change). It will also provide insights in the hydrogeological conceptual model of volcanic islands, including the significant role of the TMCFs in the recharge processes as well as the watershed hydrosedimentary responses to extreme climatic events and their respective evolution under changing climatic conditions. All data sets are available at https://doi.org/10.5281/zenodo.7983138.

Research on identification of key processes in machining process based on PageRank algorithm

Aiming at the difficulty of quantitatively evaluating the critical processes in the manufacturing process of complex mechanical products, a critical process identification method based on the PageRank algorithm is proposed with the goal of identifying key processes in the machining process. Based on the complex network theory, the error transfer network model of the machining process is established in this paper. Adopting the actual machining process as the data set of the complex network, the weights of the machining feature nodes are calculated by the PageRank ranking algorithm, and the nodes are ranked according to the weight values to assess the influence and importance of the nodes in the network model. Finally, taking the connecting rod machining process of a medium-speed marine diesel engine as an example, the results show that the method can quickly and effectively identify the key processes in the machining process.

The chromatin-associated lncREST ensures effective replication stress response by promoting the assembly of fork signaling factors

ABSTRACTBesides the well-characterized protein network involved in the replication stress response, several regulatory RNAs have been shown to play a role in this critical process. However, it has remained elusive whether they act locally at the stressed forks. Here, by investigating the RNAs localizing on chromatin upon replication stress induced by hydroxyurea, we identified a set of lncRNAs upregulated in S-phase and controlled by stress transcription factors. Among them, we demonstrate that the previously uncharacterized lncRNA lncREST (long non-coding RNA REplication STress) is transcriptionally controlled by p53 and localizes at stressed replication forks. LncREST-depleted cells experience sustained replication fork progression and accumulate un-signaled DNA damage. Under replication stress, lncREST interacts with the protein NCL and assists in engaging its interaction with RPA. The loss of lncREST is associated with a reduced NCL-RPA interaction and decreased RPA on chromatin, leading to defective replication stress signaling and accumulation of mitotic defects, resulting in apoptosis and a reduction in tumorigenic potential of cancer cells. These findings uncover the function of a lncRNA in favoring the recruitment of replication proteins to sites of DNA replication.

A generic pump-free organ-on-a-chip platform for assessment of intestinal drug absorption.

Organ-on-a-chip technology has shown great potential in disease modeling and drug evaluation. However, traditional organ-on-a-chip devices are mostly pump-dependent with low throughput, which makes it difficult to leverage their advantages. In this study, we have developed a generic, pump-free organ-on-a-chip platform consisting of a 32-unit chip and an adjustable rocker, facilitating high-throughput dynamic cell culture with straightforward operation. By utilizing the rocker to induce periodic fluid forces, we can achieve fluidic conditions similar to those obtained with traditional pump-based systems. Through constructing a gut-on-a-chip model, we observed remarkable enhancements in the expression of barrier-associated proteins and the spatial distribution of differentiated intestinal cells compared to static culture. Furthermore, RNA sequencing analysis unveiled enriched pathways associated with cell proliferation, lipid transport, and drug metabolism, indicating the ability of the platform to mimic critical physiological processes. Additionally, we tested seven drugs that represent a range of high, medium, and low in vivo permeability using this model and found a strong correlation between their Papp values and human Fa, demonstrating the capability of this model for drug absorption evaluation. Our findings highlight the potential of this pump-free organ-on-a-chip platform as a valuable tool for advancing drug development and enabling personalized medicine.