Early Stages Of Process Research Articles

Critical decisions at the early stage of start-ups: a systematic literature review

AbstractThis systematic literature review (SLR) identifies and ranks the decisions that can be considered critical for entrepreneurs at the early stage of the start-up process. The sample (N = 56) derived from the SLR contained primary publications from the A + and A journals of the VHB-Journal ranking. Deductive and inductive approaches were used to define the critical decision domains. Then, the relevance of the domains was evaluated using the frequency of the selected studies. A key implication for founders is to understand that not all decisions that could be taken in the early stage may be critical for success. Most critical seems to invest time and effort in the, what we label the internal business and human core (Core People and Product Definition) and the external business and human core (Market segment selection and Partnerships). This study depicts an integrated view of the fragmented field of critical decisions in the context of early-stage start-ups by using a SLR. Thus, it creates value for theory-building and practitioners in entrepreneurship and innovation.

Giardia fibrillarin: a bioinformatics exploration of sequence and structure.

Fibrillarin is a key nucleolar S-adenosyl-L-methionine (SAM)-dependent methyltransferase, highly conserved among species in both sequence and function. It is actively involved in numerous cellular processes, particularly in the early stages of pre-ribosomal RNA processing. Although a fibrillarin orthologue has been identified in Giardia, an intestinal protozoan parasite responsible for numerous infections worldwide, its functional and structural features in this parasite remain largely unexplored. In this study, bioinformatics tools were used to analyze the sequence and structure of Giardia fibrillarin to provide insights that could aid future experimental and therapeutic investigations. Taking advantage of the protein sequence of Giardia fibrillarin, multiple bioinformatics tools were employed to estimate its domains, nuclear and nucleolar localization signals (NLS and NoLS), post-translational modifications, phylogeny, and three-dimensional structure. The analysis revealed significant conservation of Giardia fibrillarin, showing close relationships with archaeal and parasitic amoeba orthologs. It retains essential features such as the SAM-dependent methyltransferase domain, a glycine- and arginine-rich domain, and both NLS and NoLS. While the core region of the protein is structurally conserved, the N-terminal region exhibits notable divergence. The potential for inhibition of Giardia fibrillarin by SAM competitors suggests that it could be a promising target for drug development, particularly for strains resistant to current treatments.

Visualization of Moisture Content, Reducing Sugars, and Chewiness in Bread During Oral Processing Based on Hyperspectral Imaging Technology

This study evaluated the differences in oral processing and texture perception of breads with varying compositions. The research investigated the dynamic changes in moisture content (MC), reducing sugars (RSs), and chewiness of the bolus formed from white bread (B0) and 50% whole-wheat bread (B50) during oral processing. Hyperspectral imaging (HSI) combined with chemometric methods was used to establish quantitative prediction models for MC, RSs, and chewiness, and to create visual distribution maps of these parameters. The results showed that B0 had a higher moisture content and a faster hydration rate than B50 during the initial stages of oral processing, indicating greater hydrophilicity and ease of saliva wetting. Additionally, the uniformity of moisture distribution in the bolus of B0 was higher than that of B50. B50 exhibited significantly lower RSs content and poorer distribution uniformity compared to B0. The primary differences in chewiness between the two types of bread were observed during the early stages of oral processing, with B50 requiring more chewing effort initially. This study demonstrated that HSI technology can effectively monitor and elucidate the compositional changes in food particles during oral processing, providing new insights into bread texture perception and offering a scientific basis for improving bread processing and texture.

The implementation process of decentralization of health services: a qualitative perspective from Sudan

BackgroundHealth system reform initiatives have increasingly embraced decentralization as a key trend. The implementation process and its outcomes are influenced by a myriad of factors, including economic forces, political dynamics, and ideological factors. Comprehending and carefully examining the implementation phase of decentralization and its consequences to achieve desired outcomes is crucial. Notably, this phase is often considered the weakest aspect of policy reforms, especially in developing countries. Therefore, this study aimed to explore and analyze the implementation phase of decentralization and its implications as essentials for achieving intended goals. The study objectives evolved around examining the entire decentralization as a multifaceted social and political process in Khartoum State, Sudan, from its early stages of decision-making, policy formulation, and implementation process and the influencing contextual factors.MethodsThis study was an exploratory qualitative study that employed in-depth interviews to gather perspectives of healthcare providers and policymakers, semi-structured observations, and thematic analysis. The study utilized Grindle’s framework for analysis.FindingsThis study revealed a political nature of decision-making, with a top–down approach to the implementation, which also lacked stakeholder involvement. It showed a lack of transparency, official documentation, and proper handover procedures from the Ministry of Health to the devolved hospitals during the implementation process. A conflict of interest between the federal and the state level was also reported. It is important to note that this process occurred within the context of structural adjustment program (SAP) schemes, which had already empowered the private sector in Sudan.ConclusionThis study documented the implementation process of decentralization of health services and its influencing factors. The study recommended reforming the decentralization policy through consultative stakeholder involvement and by implementing a concurrent responsibility paradigm that divides authority between the federal and state levels.

Features of the change in the thermal coefficient of electrical resistance upon heating electrically conductive composites of crystallizable polyolefins with carbon black

Objectives. To investigate electrically conductive polymer composite materials (EPCMs) based on crystallizable polyolefins and electrically conductive carbon black for the production of self-regulating heaters; to study the mechanism of the occurrence of positive and negative temperature coefficients (PTC and NTC) upon heating such composites.Methods. A comprehensive study of the structure and properties of crystallizable EPCMs with electrically conductive technical carbon was carried out. In order to measure the electrical characteristics of the composites, they were compacted into plates to model polymer heaters. Contact electrodes made of an ungreased brass mesh were embedded in their ends. The temperature dependencies of the electrical characteristics of the samples were investigated in a modified thermal chamber of an FWV 633.10 Vicat softening temperature meter. The change in the degree of crystallinity was analyzed by means of differential scanning calorimetry with a NETZSCH DSC 204 F1 Phoenix calorimeter. The dilatometric and rheological characteristics of the samples were studied using an IIRT-AM melt flow index tester.Results. It was determined that the self-regulation ability (an abnormally high positive thermal coefficient of electrical resistance) of selfregulating heaters made of composites of crystallizable polyolefins with electrically conductive technical carbon cannot be explained by the thermal expansion of EPCMs alone. It was shown that in crystallizable polyolefin-based EPCMs, the inversion of the thermal coefficients of electrical resistance (transition from PTC to NTC) is associated with a change in the aggregate state of EPCMs and the beginning of its transition to a viscous-flow state. A mechanism involving a sharp increase in the electrical resistance of self-regulating crystallizable polyolefin-based composite with electrically conductive technical carbon was proposed and substantiated. This mechanism takes into account the additional shear deformation effect produced on the crystalline phase of the EPCM by numerous expanding melt microvolumes formed at the early stages of the melting process with a minimum change in the degree of crystallinity.

Numerical simulations on non-reactive multiphase flow during the transition from vent activation to venting with vent cap fragments in 18650 lithium-ion batteries

Mandatory safety devices, prevalent in lithium-ion batteries (LIBs), enable current interrupt device (CID)-and vent-activated power-off protection by sensing the electrochemical gas production boost triggered by thermal runaway (TR). For an in-depth understanding of the early warning of safety devices, the thermodynamic and multiphase flow behaviour of gases-vent particles interaction under the non-combustion venting phase is numerically investigated. From the gas phase simulation results, the flow field structure of the counter-rotating vortex pairs (CVPs) bounded by vent cap fragments enhances the heat transfer between ambient air and the venting gas, and the local venting gas temperature can reach a drop of >100 K. The transient three-dimensional spatial evolution characteristics of vent particles interacting with vent cap fragments at the early stage of the venting process after 18650 thermal runaway-induced vent-activation is originally demonstrated, including gas temperature and velocity as well as particle size and temperature. The spatial distributions of polydisperse particle size and temperature under the process of non-combustion venting are used to characterize the ejected particles' behaviour, which reveals the particle trajectories in particle-laden streams and their heat-transfer characteristics. The results show that ejected particles with relatively high temperatures and large sizes are mainly clustered within the cell diameters, and possible thermal runaway propagation inside the module can be triggered by the smaller-size particles of higher temperature sprayed in the periphery when the blocking effect of the vent cap fragment is weakened.

Effect of Fin Configuration on the Early Stage of the Melting Process of a Phase Change Material

Thermal storage systems are essential for optimizing energy resource utilization, particularly in the current context where sustainability and efficiency are critical. Phase Change materials (PCMs) offer a promising solution for improving thermal management efficiency without additional power consumption. Considering that the low thermal conductivity of phase change materials (PCMs) is a limiting factor for heat transfer, this study employs the enthalpy-porosity method to analyze the melting characteristics of a high-Prandtl number PCM. Additionally, this study investigated the effect of varying the number of fins in the heat sink on the heat transfer rate. The material melting process was modeled by considering buoyancy effects and treating the flow as incompressible, Newtonian, transient, and laminar. Lauric acid was selected as the working material with temperature-dependent properties that were incorporated into the simulations for greater accuracy. Three different heat sink configurations were analyzed, varying the number of fins from 5 to 10 and their lengths from 0.02 meters to 0.04 meters. The objective was to optimize the cooling performance using aluminum, which was selected for its excellent balance of lightweight properties and high thermal conductivity. This analysis aimed to assess how these variations in the fin count and dimensions affect the overall heat dissipation efficiency and thermal management of the system. The inclusion of a finned heat sink within a heat exchanger has demonstrated significant efficiency, particularly in regions with substantial boundary layer development, resulting in enhanced heat transfer. These findings highlight the effectiveness of using finned heat sinks in these regions. However, an interesting observation emerged regarding the effect of increasing the number of fins over long periods. Although initially beneficial, a larger number of fins eventually led to a reduced performance over time, notably affecting the thermal storage capacity and molten liquid mass production. Additionally, this study elucidates the influence of natural convection on thermal boundary layer development, highlighting the complexity of the heat transfer processes.

SydR, a redox-sensing MarR-type regulator of Sinorhizobium meliloti, is crucial for symbiotic infection of Medicago truncatula roots.

Rhizobia associate with legumes and induce the formation of nitrogen-fixing nodules. The regulation of bacterial redox state plays a major role in symbiosis, and reactive oxygen species produced by the plant are known to activate signaling pathways. However, only a few redox-sensing transcriptional regulators (TRs) have been characterized in the microsymbiont. Here, we describe SydR, a novel redox-sensing TR of Sinorhizobium meliloti that is essential for the establishment of symbiosis with Medicago truncatula. SydR, a MarR-type TR, represses the expression of the adjacent gene SMa2023 in growing cultures, and this repression is alleviated by NaOCl, tert-butyl hydroperoxide, or H2O2 treatment. Transcriptional psydR-gfp and pSMa2023-gfp fusions, as well as gel shift assays, showed that SydR binds two independent sites of the sydR-SMa2023 intergenic region. This binding is redox-dependent, and site-directed mutagenesis demonstrated that the conserved C16 is essential for SydR redox sensing. The inactivation of sydR did not alter the sensitivity of S. meliloti to NaOCl, tert-butyl hydroperoxide, or H2O2, nor did it affect the response to oxidants of the roGFP2-Orp1 redox biosensor expressed within bacteria. However, in planta, ΔsydR mutation impaired the formation of root nodules. Microscopic observations and analyses of plant marker gene expression showed that the ΔsydR mutant is defective at an early stage of the bacterial infection process. Altogether, these results demonstrated that SydR is a redox-sensing MarR-type TR that plays a key role in the regulation of nitrogen-fixing symbiosis with M. truncatula.IMPORTANCEThe nitrogen-fixing symbiosis between rhizobia and legumes has an important ecological role in the nitrogen cycle, contributes to nitrogen enrichment of soils, and can improve plant growth in agriculture. This interaction is initiated in the rhizosphere by a molecular dialog between the two partners, resulting in plant root infection and the formation of root nodules, where bacteria reduce the atmospheric nitrogen into ammonium. This symbiosis involves modifications of the bacterial redox state in response to reactive oxygen species produced by the plant partner. Here, we show that SydR, a transcriptional regulator of the Medicago symbiont Sinorhizobium meliloti, acts as a redox-responsive repressor that is crucial for the development of root nodules and contributes to the regulation of bacterial infection in S. meliloti/Medicago truncatula symbiotic interaction.

YOLO-DHGC: Small Object Detection Using Two-Stream Structure with Dense Connections.

Small object detection, which is frequently applied in defect detection, medical imaging, and security surveillance, often suffers from low accuracy due to limited feature information and blurred details. This paper proposes a small object detection method named YOLO-DHGC, which employs a two-stream structure with dense connections. Firstly, a novel backbone network, DenseHRNet, is introduced. It innovatively combines a dense connection mechanism with high-resolution feature map branches, effectively enhancing feature reuse and cross-layer fusion, thereby obtaining high-level semantic information from the image. Secondly, a two-stream structure based on an edge-gated branch is designed. It uses higher-level information from the regular detection stream to eliminate irrelevant interference remaining in the early processing stages of the edge-gated stream, allowing it to focus on processing information related to shape boundaries and accurately capture the morphological features of small objects. To assess the effectiveness of the proposed YOLO-DHGC method, we conducted experiments on several public datasets and a self-constructed dataset. Exceptionally, a defect detection accuracy of 96.3% was achieved on the Market-PCB public dataset, demonstrating the effectiveness of our method in detecting small object defects for industrial applications.

Embodied Semantics: Early Simultaneous Motor Grounding in First and Second Languages

Background/Objectives: Although the embodiment of action-related language is well-established in the mother tongue (L1), less is known about the embodiment of a second language (L2) acquired later in life through formal instruction. We used the high temporal resolution of ERPs and topographic ERP analyses to compare embodiment in L1 and L2 and to investigate whether L1 and L2 are embodied with different strengths at different stages of linguistic processing. Methods: Subjects were presented with action-related and non-action-related verbs in a silent reading task. Subjects were late French–German and German–French bilinguals, respectively, and we could therefore collapse across languages to avoid common confounding between language (French and German) and order of acquisition (L1, L2). Results: We could show distinct effects of embodiment and language. Embodiment affected only the sensory and lexical stages of processing with increased strength and power of the N1 component for motor vs. non-motor verbs, and language affected the lexical and semantic stages of processing with stronger P2/N400 components for L2 than for L1. Non-motor verbs elicited a stronger P1 component in L2. Conclusions: Our results suggest that processing words in L2 requires more effortful processing. Importantly, L1 and L2 are not embodied differently, and embodiment affects early and similar stages of processing in L1 and L2, possibly integrating other process of action–language interaction

Few-femtosecond time-resolved study of the UV-induced dissociative dynamics of iodomethane

Ultraviolet (UV) light that penetrates our atmosphere initiates various photochemical and photobiological processes. However, the absence of extremely short UV pulses has so far hindered our ability to fully capture the mechanisms at the very early stages of such processes. This is important because the concerted motion of electrons and nuclei in the first few femtoseconds often determines molecular reactivity. Here we investigate the dissociative dynamics of iodomethane following UV photoexcitation, utilizing mass spectrometry with a 5 fs time resolution. The short duration of the UV pump pulse (4.2 fs) allows the ultrafast dynamics to be investigated in the absence of any external field, from well before any significant vibrational displacement occurs until dissociation has taken place. The experimental results combined with semi-classical trajectory calculations provide the identification of the main dissociation channels and indirectly reveal the signature of a conical intersection in the time-dependent yield of the iodine ion. Furthermore, we demonstrate that the UV-induced breakage of the C-I bond can be prevented when the molecule is ionized by the probe pulse within 5 fs after the UV excitation, showcasing an ultrafast stabilization scheme against dissociation.

Endoscopic diagnosis of laryngeal precancerous lesions and early laryngeal cancer

ISince laryngeal cancer currently occupies a leading position in frequency of occurrence among all tumors of the upper respiratory tract of modern humans, the importance of its detection at an early stage of development cannot be overestimated. Existing diagnostic methods using rigid endoscopes, including direct and indirect laryngoscopy, have significant limitations in a number of patients. The use of modern video endoscopic technology allows diagnosing precancerous lesions and laryngeal cancer at an early stage of the tumor process, which significantly expands the possibilities of minimally invasive organ-preserving treatment.

Multiple mechanisms enable broad-spectrum activity of the Pelargonium sidoides root extract EPs 7630 against acute respiratory tract infections.

There is clinical evidence showing that the Pelargonium sidoides root extract EPs 7630 is a safe and effective treatment for a range of acute infectious respiratory illnesses. Moreover, EPs 7630 has been shown to reduce the use of antibiotics, which is important in the context of rising antibiotic resistance levels. A wide range of mechanisms appears to contribute to the beneficial effects of EPs 7630, e.g. antibacterial, antiviral, immunomodulatory, and epithelial barrier effects. This broad spectrum of pharmacological activities seems to enable the clinical activity of EPs 7630 against multiple respiratory infections. In particular, the combination of antiviral and immunomodulatory effects may enable EPs 7630 to tackle acute viral respiratory infections both in early stages of the disease process, which are driven by virus replication, as well as in later stages, which are caused by an overshooting immune response. Hence, EPs 7630 is a prime example of a plant extract with evidence-based clinical efficacy, including a solid understanding of the underlying mechanisms of action. The example of EPs 7630 demonstrates that plant extracts have a potential role as evidence-based clinical treatments and that they deserve pre-clinical and clinical testing and investigation in the same way as any other drug class.

Control charts for monitoring the capability of unstable process

Stability is an important criterion to be investigated at the early stage of any industrial process and stable processes are usually preferred over unstable ones. But a process can be unstable and nevertheless capable and, therefore, there is a clear need to monitor such situations to ensure an acceptable capability. In this study we introduce, in a first step, a new Shewhart-type control chart for normal processes based on the yield index S pk to monitor the capability of potentially unstable processes and then, in a second step, we extend it using an Exponentially Weighted Moving Average (EWMA) scheme. Moreover, the optimal values of the control parameters are obtained using a nonlinear optimization problem for which the out-of-control average run length is the objective function. The introduced charts’ sensitivity is examined for deterministic shift sizes. Numerical and graphical analyses are given to display the features of the proposed charts. A simulation study shows, how in such a situation, the introduced tool is successful to recognize changes in the process capability.

Proposed framework for medication delivery system in the Jordanian public health sector

BackgroundIn Jordan, the confluence of traffic congestion and overcrowding in public hospitals poses a significant challenge for patients to collect their medications timely. This challenge was further intensified during the COVID-19 pandemic. Recognizing this issue, the Ministry of Health (MOH) and Electronic Health Solutions (EHS) intend to establish a Medication Delivery System (MDS), designed to provide patients with home delivery of medications and ensure proper treatment. This paper outlines a comprehensive framework to guide requirements engineers in devising an effective MDS framework, with a focus on expediting the development and testing processes and mitigating the risks associated with constructing such a system.MethodThe proposed methodology entails a robust, structured approach to requirements development for an MDS that integrates an electronic health record system, billing system, pharmacy application, the patient-oriented My Hakeem app, and a delivery tracking system. The requirements elicitation and analysis processes were undertaken by a multidisciplinary committee from MOH and EHS teams, ensuring a diverse understanding of stakeholder needs and expectations. The requirement specifications were meticulously documented via a data dictionary, unified modeling language (UML), and context diagrams. The quality and accuracy of the requirements were verified through an extensive validation process, involving thorough review by various EHS teams and the MOH committee.ResultsThe MDS was implemented across numerous MOH facilities within a timeline that was a third of the original projection, leveraging the same level of resources and expertise. Post the requirements development phase, there were no changes requested by any stakeholders, indicating a high level of requirement accuracy and satisfaction.ConclusionThe study illustrates that our proposed methodology significantly results in a comprehensive, well-documented, and validated set of requirements, which streamlines the development and testing phases of the project and effectively eliminates requirement errors at an early stage of the requirements development process.

Connector hubs in semantic network contribute to creative thinking.

Semantic memory offers a rich repository of raw materials (e.g., various concepts and connections between concepts) for creative thinking, represented as a semantic network. Similar to other networks, the semantic network exhibits a modular structure characterized by modules with dense internal connections and sparse connections between them. This organizational principle facilitates the routine storage and retrieval of information but may impede creativity. The present study investigated the effect of hub concepts with varying connection patterns on creative thinking from the perspective of a modular structured semantic network. By analyzing a large-scale semantic network, connector hubs (C-hubs) and provincial hubs (P-hubs) were identified based on their intra- and intermodule connections. These hubs were used as cue words in the alternative uses task, a widely used measure of creative thinking. Across four experiments, behavioral and neural evidence indicated that C-hubs facilitate the generation of more novel and remote ideas compared to P-hubs. However, this effect is predominantly observed in the early stage of the creative thinking process, involving changes in brain activation and functional connectivity in core regions of the default mode network and the frontoparietal network, including the dorsolateral prefrontal cortex, angular gyrus, and precuneus. Neural findings suggest that the superior performance of C-hubs relies on stronger interactions between automatic spreading activation, controlled semantic retrieval, and attentional regulation of salient information. These results provide insight into how concepts with varying semantic connection patterns facilitate and constrain different stages of the creative thinking process through the modular structure of semantic network. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Predictive Role of visual attention bias in aggressive driving decisions among violation-involved drivers on attitudes of right-of-way

This study, based on dual-process theory, explores the aggressive driving decision-making characteristics and cognitive processing of violation-involved drivers in right-of-way infringement scenarios. It aims to identify an eye-movement indicator that can predict drivers’ prosocial behaviors. The study recruited 75 drivers aged 19–58 years, who completed a video-based aggressive driving decision-making test and the Driver Attitudes of Right-of-way Questionnaire (DARQ). The results indicate that age moderates the relationship between violation history and visual attentional bias. Younger drivers with a history of violations exhibit an attentional bias towards aggressive words, whereas older drivers do not. After controlling for age, violation-involved drivers demonstrated a higher rate of aggressive decision-making, especially in situations with very short lane-change time headway. Visual attentional bias towards aggressive words can effectively predict positive emotions in attitudes towards the right-of-way. This suggests that early eye movement indicators during the driving decision-making process represent a form of socioemotional characteristic. The more positive the driver’s right-of-way attitude, the stronger their prosocial behavior and the weaker their intuitive impulsiveness during the early cognitive processing stages of driving decision-making. This indicates that the driving decision-making eye-movement assessment paradigm is an objective and effective method for evaluating drivers’ pro-sociality.

Internal radiation effect on semiconductor β-Ga2O3 crystals grown by the VB Method and anisotropic thermal stress

Gallium oxide crystals are semitransparent semiconductors with good optical and electrical properties, which allow their use for several technological applications. During the growth process of β-Ga2O3 crystals, internal radiation plays a crucial role that affects the growth process and then the crystal quality. In this work, the effect of the melt and the crystal transparency on the vertical Bridgman growth of β-Ga2O3 oxide is thoroughly studied. Using a global 2D/3D finite element model, temperature, melt flow, melt-crystal interface, and three-dimensional anisotropic thermal stress are computed at different growth stages. At each stage, four cases are considered, namely, opaque melt and crystal, semi-transparent melt and opaque crystal, semitransparent crystal and opaque melt, and finally semitransparent melt and crystal. The role of internal radiation in each case at different growth stages is then highlighted separately and then coupled together. It was found that the melt-crystal interface is shifted from a convex shape at the early stage to a nearly plane and then to a concave shape at the last stage. The melt flow is then changed from two rolls pattern at the beginning to a single-roll structure at the last stage. Thermal stress of the as-grown ingot is decreased during the growth due to the decrease of temperature non-linearities. Internal radiation inside the crystal acts to increase the melt-crystal interface convexity at the early and middle stages of the growth process and leads to a decrease in its concavity at the final stage. However, the melt transparency leads to the opposite effects, i.e., it decreases the interface convexity at the early stage and increases the interface concavity at the final stage. As a result, for semitransparent crystal and melt, the interface is between the two previous cases. The calculated thermal stresses are found to be more affected by the transparency of the crystal than the melt as the absorption coefficient of β-Ga2O3 crystal is smaller than that of the melt. At all stages, the thermal stresses are found to be larger for the opaque case due to the increase of temperature non-linearities in the crystal. Large values are found at the bottom and the lower part of the periphery. Furthermore, internal radiation inside the melt plays a major role during the early growth stage due to the large liquid volume. It reduces the melt flow intensity close to the free surface where the shear stress is combined with the buoyant force and leads to the flattening of the interface decreasing then the radial temperature gradients, which leads to small attenuation of the thermal stress. At the final stage, the transparency of the melt plays the opposite role due to the increase of the interface concavity which leads to an increase in both of the temperature gradients and the thermal stress inside the crystal. Due to the crystal anisotropy, and especially to the large thermal expansion coefficient in the [010] direction, the 3D thermal stress values are found to be larger in this direction, especially in the bottom part of the ingot. Comparisons with available experimental and numerical works are provided in this paper.

ChemAP: predicting drug approval with chemical structures before clinical trial phase by leveraging multi-modal embedding space and knowledge distillation

Recent studies showed that the likelihood of drug approval can be predicted with clinical data and structure information of drug using computational approaches. Predicting the likelihood of drug approval can be innovative and of high impact. However, models that leverage clinical data are applicable only in clinical stages, which is not very practical. Prioritizing drug candidates and early-stage decision-making in the de novo drug development process is crucial in pharmaceutical research to optimize resource allocation. For early-stage decision-making, we need a computational model that uses only chemical structures. This seemingly impossible task may utilize the predictive power with multi-modal features including clinical data. In this work, we introduce ChemAP (Chemical structure-based drug Approval Predictor), a novel deep learning scheme for drug approval prediction in the early-stage drug discovery phase. ChemAP aims to enhance the possibility of early-stage decision-making by enriching semantic knowledge to fill in the gap between multi-modal and single-modal chemical spaces through knowledge distillation techniques. This approach facilitates the effective construction of chemical space solely from chemical structure data, guided by multi-modal knowledge related to efficacy, such as clinical trials and patents of drugs. In this study, ChemAP achieved state-of-the-art performance, outperforming both traditional machine learning and deep learning models in drug approval prediction, with AUROC and AUPRC scores of 0.782 and 0.842 respectively on the drug approval benchmark dataset. Additionally, we demonstrated its generalizability by outperforming baseline models on a recent external dataset, which included drugs from the 2023 FDA-approved list and the 2024 clinical trial failure drug list, achieving AUROC and AUPRC scores of 0.694 and 0.851. These results demonstrate that ChemAP is an effective method in predicting drug approval only with chemical structure information of drug so that decision-making can be done at the early stages of drug development process. To the best of our knowledge, our work is the first of its kind to show that prediction of drug approval is possible only with structure information of drug by defining the chemical space of approved and unapproved drugs using deep learning technology.

Removal of raffinose and stachyose from soy-based beverages using soluble and immobilized MelA α-D-galactosidase from Lactiplantibacillus plantarum WCFS1

The hydrolysis of α-galactose-carbohydrates in soy-based beverages using the enzyme MelA α-D-galactosidase (Lp_3485) from Lactiplantibacillus plantarum WCFS1 is presented. MelA is a highly unstable trimeric enzyme whose activity and stability are strongly dependent on the dilution and polarity of the reaction medium. Considering this, the enzyme was immobilized and stabilized using different immobilization protocols. Post-immobilization techniques consisting of cross-linking with different polyfunctional polymers were used. The optimal derivative was used to hydrolyse different oligosaccharides of the raffinose family (raffinose and stachyose) present in soy drink preparations. Remarkably, MelA showed specific activity and high hydrolytic efficiency towards RFOs in soy-based beverages at a relatively low temperature (20 °C). Therefore, these results suggest that this enzyme could be preferentially used in the early stage of soybean processing to remove RFOs from soy-based beverages and soy-derived products, thereby improving their nutritional value.