Target Structure Research Articles

Study on circular scanning for cross-scale micro/nanoscratching machining

Large-scale scanning probe can facilitate fabricating cross-scale micro/nano structures. However, the processing of complex two-dimensional patterns usually encounters challenges including numerous machining feature points and probe jumps, which results in low efficiency, as well as poor machining quality. Therefore, a circular scanning method based on corner point extraction (CSCE) was proposed in this study for programming the probe path and reducing the number of probe jumps. Before the machining, the target structures or images were converted into raw data points through image processing, and then the data was refined by corner point extraction for obtaining the machining points. Subsequently, the machining points were arranged in the order of a circular scanning algorithm to get the probe path. Using CSCE, the probe jump was only 1 time for processing an H-shaped pattern. By comparison with the circular scanning method based on intersection point extraction (CSIE) for the H pattern, the number of machining points in CSCE was reduced from 82 to 12, and the machining time was shortened from 17.15 s to 3.17 s. Consequently, CSCE can enable efficient and high-quality fabrication of cross-scale micro/nanostructures.

Poisson Effect‐Assisted Replication Lithography for Rapid Fabrication of Three‐Dimensional Microstructures

Demands for micro‐ and nano‐fabrication techniques have been increasing over recent decades due to their foundational importance in fields such as electronics, sensors, displays, biotechnologies, and energy technologies. Still, the rapid and efficient fabrication of complex 3D microstructures has long been a challenge due to the inherent limitations of conventional imprint lithography and the slow fabrication speed of maskless lithography systems using femtosecond lasers. This study introduces a novel lithographic replication method for the rapid replication of intricate 3D microstructures with closed‐loops by leveraging the Poisson effect‐driven lateral deformation of soft molds. Specifically, the suggested technique employs an elastomeric soft mold, engraved with negative cavity parts of the target structure separated by intentional gaps. Lateral deformation of the material allows the separated cavities to assemble for replication of target microstructure and defectless release from the soft mold. In addition to the experimental demonstrations of the proposed method using well‐known materials like polydimethysliloxane (PDMS) for the soft mold and UV‐curable polyurethane acrylate (PUA) for replication, essential considerations such as material selection and master mold design are discussed. The presented method not only broadens the capabilities of imprint lithographic techniques but also holds promise for the large scale, continuous fabrication of complex 3D microstructures.

Effects of task repetition with grammatizing on oral task performance and knowledge development

Abstract This study compared the effects of task repetition only (TR), task repetition with grammatizing (TR+GR), and grammatization with no task repetition (GR) on 94 EFL learners’ oral task performances. Participants’ productions were measured both in terms of complexity, accuracy, and fluency as well as receptive knowledge (measured by an error correction test) and productive knowledge (measured by a sentence-level oral production test) development. Immediately after performing a narrative task, the TR+GR and GR learners were required to restore the target structure, namely the English regular past tense, which had been deleted in a grammatized text. Learners in the TR group received no grammatization, and only the TR+GR and TR groups repeated the same task twice. Results revealed that although both TR conditions led to enhanced receptive knowledge, the TR+GR performed better than the TR in fostering learners’ receptive knowledge and improving accuracy and productive knowledge at a delayed posttest. The GR group improved their receptive knowledge in the immediate posttest, but this improvement tailed off in the delayed posttest. Lastly, the TR+GR group could also improve the complexity and accuracy of their narrative task performances–albeit at the expense of fluency.

Evaluation of Novel Benzo-annelated 1,4-dihydropyridines as MDR Modulators in Cancer Cells.

Multidrug resistance (MDR) is the main problem in anticancer therapy today. Causative transmembrane efflux pumps in cancer cells have been reconsidered as promising anticancer target structures to restore anticancer drug sensitivity by various strategies, including MDR modulators. MDR modulators interfere with the efflux pumps and improve the cellular efficiency of chemotherapeutics. So far, only a few candidates have gone through clinical trials with disappointing results because of low specificity and toxic properties. This study aimed to find Novel MDR modulators to effectively combat multidrug resistance in cancer cells. We synthesized various novel benzo-annelated 1,4-dihydropyridines to evaluate them as MDR modulators towards ABCB1 in cancer cells. Synthesized compounds were purified by column chromatography. The MDR modulation of ABCB1 was determined in cellular efflux assays using the flow cytometry technique and cellular fluorescent measurements by the use of each fluorescent substrate. Compounds were yielded in a two-step reaction with structurally varied components. Further, substituent- dependent effects on the determined MDR inhibiting properties towards ABCB1 were discussed. Cellular studies prove that there is no toxicity or restoration of cancer cell sensitivity towards the used anticancer drug. Novel MDR modulators could be identified with favorable methoxy and ester group functions. Their use in both ABCB1 non-expressing and overexpressing cells proves a selective toxicity-increasing effect of the applied anticancer agent in the ABCB1 overexpressing cells, whereas the toxicity effect of the anticancer drug was almost unchanged in the non-expressing cells. These results qualify our novel compounds as perspective anticancer drugs compared to MDR modulators with nonselective toxicity properties.

Deformation mechanism of metastable oriented grains in high-purity tantalum under different strain paths

High-purity tantalum is used as the sputtering target material for integrated circuits, requiring fine grains and random texture. Understanding different orientation deformation mechanisms, especially the metastable orientation (here {112} crystallographic orientations), is beneficial for controlling the structure of tantalum target materials.This paper employs EBSD and crystallographic calculations to regulate the grain deformation behavior by introducing a reverse strain at 135° clock rolling. The deformation behavior and dislocation density distribution of the metastable oriented grains under different strain paths are quantitatively analyzed. Results show that unidirectional rolling (UR) generates stress concentration, causing an uneven distribution of geometrically necessary dislocation density. The splitting behavior of {112} and {111} grains is promoted, and they have similar deformation behavior in UR process, while the deformation of {100} oriented grains is significantly suppressed. Furthermore, changing the strain path promotes the splitting of {100} grains, and makes the {112} change from the soft orientation to the hard orientation. This change makes it easier to start multi-slipping, resulting in a more uniform deformation. Additionally, crystallographic calculations show that Schmid factor is ineffective in explaining the strain localization problem in BCC metals. However, Schmid factor difference ratio makes it possible to analyze the distribution of dislocation density in local regions through the quantitative calculation of multi- slipping.

Broad-Spectrum In Vitro Activity of Nα-aroyl-N-aryl-Phenylalanine Amides against Non-Tuberculous Mycobacteria and Comparative Analysis of RNA Polymerases

This study investigates the in vitro activity of Nα-aroyl-N-aryl-phenylalanine amides (AAPs), previously identified as antimycobacterial RNA polymerase (RNAP) inhibitors, against a panel of 25 non-tuberculous mycobacteria (NTM). The compounds, including the hit compound MMV688845, were selected based on their structural diversity and previously described activity against mycobacteria. Bacterial strains, including the M. abscessus complex, M. avium complex, and other clinically relevant NTM, were cultured and subjected to growth inhibition assays. The results demonstrate significant activity against the most common NTM pathogens from the M. abscessus and M. avium complexes. Variations in activity were observed against other NTM species, with for instance M. ulcerans displaying high susceptibility and M. xenopi and M. simiae resistance to AAPs. Comparative analysis of RNAP β and β′ subunits across mycobacterial species revealed strain-specific polymorphisms, providing insights into differential compound susceptibility. While conservation of target structures was observed, differences in compound activity suggested influences beyond drug–target interactions. This study highlights the potential of AAPs as effective antimycobacterial agents and emphasizes the complex interplay between compound structure, bacterial genetics, and in vitro activity.

A Pseudo Planar Heterojunction Structure for Eco‐Friendly Printable Organic Solar Cells Achieving 19.05% Efficiency

AbstractObtaining a well‐accurate vertical distribution active layer morphology through the air‐printing process is an essential task for achieving efficient scalable large‐area organic solar cells (OSCs). In this target, the desired and controllable pseudo planar heterojunction (PPHJ) active layer structure with suitable phase separation is developed by pre‐deposited D18‐Cl layer under the PM6:BTP‐eC9 film via an eco‐friendly manufacturing method. The addition of the D18‐Cl regulates molecular crystallization and leads to an ideal vertical stratification while simultaneously suppressing voltage loss, optimizing energetic disorder, and carrier management. Impressively, the optimal PPHJ devices perform superior power conversion efficiencies (PCEs) of 19.05% (100 nm), 17.33% (300 nm), and 14.14% (4 cm2) compared to the BHJ devices. Importantly, the PPHJ OSCs also exhibit an impressive extrapolated T80 (the time required to reach 80% of initial PCE) of long‐time storage and operational stability, as well as thermal stability.

Synchronous excitation in the superficial and deep layers of the medial entorhinal cortex precedes early sharp waves in the neonatal rat hippocampus.

Early Sharp Waves (eSPWs) are the earliest pattern of network activity in the developing hippocampus of neonatal rodents. eSPWs were originally considered to be an immature prototype of adult SPWs, which are spontaneous top-down hippocampal events that are self-generated in the hippocampal circuitry. However, recent studies have shifted this paradigm to a bottom-up model of eSPW genesis, in which eSPWs are primarily driven by the inputs from the layers 2/3 of the medial entorhinal cortex (MEC). A hallmark of the adult SPWs is the relay of information from the CA1 hippocampus to target structures, including deep layers of the EC. Whether and how deep layers of the MEC are activated during eSPWs in the neonates remains elusive. In this study, we investigated activity in layer 5 of the MEC of neonatal rat pups during eSPWs using silicone probe recordings from the MEC and CA1 hippocampus. We found that neurons in deep and superficial layers of the MEC fire synchronously during MEC sharp potentials, and that neuronal firing in both superficial and deep layers of the MEC precedes the activation of CA1 neurons during eSPWs. Thus, the sequence of activation of CA1 hippocampal neurons and deep EC neurons during sharp waves reverses during development, from a lead of deep EC neurons during eSPWs in neonates to a lead of CA1 neurons during adult SPWs. These findings suggest another important difference in the generative mechanisms and possible functional roles of eSPWs compared to adult SPWs.

Multimodal protein representation learning and target-aware variational auto-encoders for protein-binding ligand generation

Without knowledge of specific pockets, generating ligands based on the global structure of a protein target plays a crucial role in drug discovery as it helps reduce the search space for potential drug-like candidates in the pipeline. However, contemporary methods require optimizing tailored networks for each protein, which is arduous and costly. To address this issue, we introduce TargetVAE, a target-aware variational auto-encoder that generates ligands with desirable properties including high binding affinity and high synthesizability to arbitrary target proteins, guided by a multimodal deep neural network built based on geometric and sequence models, named Protein Multimodal Network (PMN), as the prior for the generative model. PMN unifies different representations of proteins (e.g. primary structure—sequence of amino acids, 3D tertiary structure, and residue-level graph) into a single representation. Our multimodal architecture learns from the entire protein structure and is able to capture their sequential, topological, and geometrical information by utilizing language modeling, graph neural networks, and geometric deep learning. We showcase the superiority of our approach by conducting extensive experiments and evaluations, including predicting protein-ligand binding affinity in the PBDBind v2020 dataset as well as the assessment of generative model quality, ligand generation for unseen targets, and docking score computation. Empirical results demonstrate the promising and competitive performance of our proposed approach. Our software package is publicly available at https://github.com/HySonLab/Ligand_Generation.

R-Matrix calculations for opacities: II. Photoionization and oscillator strengths of iron ion FeXVII, FeXVIII and FeXIX

Abstract Iron is the dominant heavy element that plays an important role in radiation transport in stellar interiors. Owing to its abundance and large number of bound levels and transitions, iron ions determine the opacity more than any other astrophysically abundant element. A few iron ions constitute the abundance and opacity of iron at the base of the convection zone (BCZ) at the boundary between the solar convection and radiative zones, and are the focus of the present study. Together, Fe xvii , Fe xviii and Fe xix contribute 85% of iron ion fractions 20%, 39% and 26% respectively, at the BCZ physical conditions of temperature T ∼ 2.11 × 106K and electron density Ne = 3.1 × 1022cc. We report heretofore the most extensive R-matrix atomic calculations for these ions for bound-bound and bound-free transitions, the two main processes of radiation absorption. We consider wavefunction expansions with 218 target or core ion fine structure levels of Fe xviii for Fe xvii , 276 levels of Fe xix for Fe xviii , in the Breit-Pauli R-matrix (BPRM) approximation, and 180 LS terms (equivalent to 415 fine structure levels) of Fe xx for Fe xix calculations. These large target expansions which includes core ion excitations to n=2,3,4 complexes enable accuracy and convergence of photoionization cross sections, as well as inclusion of high lying resonances. The resulting R-matrix datasets include 454 bound levels for Fe xvii , 1,174 levels for Fe xviii , and 1,626 for Fe xix up to n ≤ 10 and l=0 - 9. Corresponding datasets of oscillator strengths for photoabsorption are: 20,951 transitions for Fe xvii , 141,869 for Fe xviii , and 289,291 for Fe xix . Photoionization cross sections have obtained for all bound fine structure levels of Fe xvii and Fe xviii , and for 900 bound LS states of Fe xix . Selected results demonstrating prominent characteristic features of photoionization are presented, particularly the strong Seaton PEC (photoexcitation-of-core) resonances formed via high-lying core excitations with ∆n = 1 that significantly impact bound-free opacity.

Click Chemistry with Cell-Permeable Fluorophores Expands the Choice of Bioorthogonal Markers for Two-Color Live-Cell STED Nanoscopy.

STED nanoscopy allows for the direct observation of dynamic processes in living cells and tissues with diffraction-unlimited resolution. Although fluorescent proteins can be used for STED imaging, these labels are often outperformed in photostability by organic fluorescent dyes. This feature is especially crucial for time-lapse imaging. Unlike fluorescent proteins, organic fluorophores cannot be genetically fused to a target protein but require different labeling strategies. To achieve simultaneous imaging of more than one protein in the interior of the cell with organic fluorophores, bioorthogonal labeling techniques and cell-permeable dyes are needed. In addition, the fluorophores should preferentially emit in the red spectral range to reduce the potential phototoxic effects that can be induced by the STED light, which further restricts the choice of suitable markers. In this work, we selected five different cell-permeable organic dyes that fulfill all of the above requirements and applied them for SPIEDAC click labeling inside living cells. By combining click-chemistry-based protein labeling with other orthogonal and highly specific labeling methods, we demonstrate two-color STED imaging of different target structures in living specimens using different dye pairs. The excellent photostability of the dyes enables STED imaging for up to 60 frames, allowing the observation of dynamic processes in living cells over extended time periods at super-resolution.

TECHNOLOGY AIDED ACTIVITIES FOR JUNIOR HIGH SCHOOL: ORAL COMMUNICATION SKILLS IN FOCUS

This study aims to explore whether students perceive that the technology aided activities for Junior High School support the development of their oral speaking skills, whether students consider that the out-of-class speaking activities contributed to building their level of confidence with respect to using the target structures and vocabulary in the classroom, and the advantages and/or challenges they perceive in using computer-mediated communicative out-of-class activities to improve their speaking skills during the pandemic. A further aim of this study is to investigate whether the use of technology aided activities out-of-class speaking activities supports the development of students willingness to communicate, measured by using students performance on different online activities. The research was conducted in selected public Junior High School who were chosen among Junior High School students on a voluntary basis. The data for this research were collected via in-depth interview, which was conducted at the middle of the study. Also, the study showed that there was a significant contribution to the students willingness to communicate in the target language as they became more confident as well as more comfortable speaking English. KEY WORDS: Technology, aided, English, activities, junior high school, oral communication, skills, focus

Is Syntactic Priming from Multiple Speakers Stronger?

Syntactic priming in dialogue occurs when exposure to a particular syntactic structure implicitly induces a speaker’s subsequent preference for the same syntactic structures in their own speech. Here, we asked whether this priming effect is boosted when individuals are primed by several different speakers as opposed to one. In an initial baseline session involving a picture description task, we assessed adult participants’ production of double object/DO (vs. prepositional/PO) dative and passive (vs. active) transitive structures. Subsequently, participants played a picture description and verification game, in turns, with six other players (confederates). During verification turns, confederates primed participants by using DO and passive utterances. Crucially, participants were primed either by a single confederate (single-speaker priming condition, SSP) or by five confederates (multi-speaker priming condition, MSP). Across conditions, the same priming stimuli were presented in the same order, leaving speaker source/variation as the only different feature. The degree to which participants were primed for the target structures compared to baseline was measured. Results indicated a robust priming effect in both conditions. Nevertheless, the increase in the target structures’ use did not differ significantly between the SSP and MSP conditions, suggesting that speaker variation did not promote stronger priming.

Neuroprotection of Cholinergic Neurons with a Tau Aggregation Inhibitor and Rivastigmine in an Alzheimer's-like Tauopathy Mouse Model.

Basal forebrain cholinergic dysfunction, most likely linked with tau protein aggregation, is a characteristic feature of Alzheimer's disease (AD). Recent evidence suggests that tau protein is a putative target for the treatment of dementia, and the tau aggregation inhibitor, hydromethylthionine mesylate (HMTM), has emerged as a potential disease-modifying treatment. However, its efficacy was diminished in patients already receiving approved acetylcholinesterase inhibitors. In this study, we ask whether this negative interaction can also be mimicked in experimental tau models of AD and whether the underlying mechanism can be understood. From a previous age profiling study, 6-month-old line 1 (L1) tau transgenic mice were characterized by a severe reduction in several cholinergic markers. We therefore assessed whether long-term pre-exposure with the acetylcholinesterase inhibitor rivastigmine alone and in conjunction with the tau aggregation inhibitor HMTM can reverse cholinergic deficits in L1. Rivastigmine and HMTM, and combinations of the two compounds were administered orally for 11 weeks to both L1 and wild-type mice. The brains were sectioned with a focus on the basal forebrain, motor cortex and hippocampus. Immunohistochemical staining and quantification of choline acetyltransferase (ChAT), tyrosine kinase A (TrkA)-positive neurons and relative optical intensity (ROI) for vesicular acetylcholine transporter (VAChT), and acetylcholinesterase (AChE) reactivity confirmed reversal of the diminished cholinergic phenotype of interneurons (nucleus accumbens, striatum) and projection neurons (medial septum, nucleus basalis magnocellularis) by HMTM, to a greater extent than by rivastigmine alone in L1 mice. Combined administration did not yield additivity but, in most proxies, led to antagonistic effects in which rivastigmine decreased the benefits shown with HMTM alone. Local markers (VAChT and AChE) in target structures of the basal forebrain, motor cortex and hippocampal CA3 seemed to be normalized by HMTM, but not by rivastigmine or the combination of both drugs. HMTM, which was developed as a tau aggregation inhibitor, strongly decreased the tau load in L1 mice, however, not in combination with rivastigmine. Taken together, these data confirm a cholinergic phenotype in L1 tau transgenic mice that resembles the deficits observed in AD patients. This phenotype is reversible by HMTM, but at the same time appears to be subject to a homeostatic regulation induced by chronic pre-treatment with an acetylcholinesterase inhibitor, which interferes with the efficacy of HMTM. The strongest phenotypic reversal coincided with a normalization of the tau load in the cortex and hippocampus of L1, suggesting that tau accumulation underpins the loss of cholinergic markers in the basal forebrain and its projection targets.

Self-replication via tile self-assembly

AbstractIn this paper we present a model containing modifications to the Signal-passing Tile Assembly Model (STAM), a tile-based self-assembly model whose tiles are capable of activating and deactivating glues based on the binding of other glues. These modifications consist of an extension to 3D, the ability of tiles to form “flexible” bonds that allow bound tiles to rotate relative to each other, and allowing tiles of multiple shapes within the same system. We call this new model the STAM*, and we present a series of constructions within it that are capable of self-replicating behavior. Namely, the input seed assemblies to our STAM* systems can encode either “genomes” specifying the instructions for building a target shape, or can be copies of the target shape with instructions built in. A universal tile set exists for any target shape (at scale factor 2), and from a genome assembly creates infinite copies of the genome as well as the target shape. An input target structure, on the other hand, can be “deconstructed” by the universal tile set to form a genome encoding it, which will then replicate and also initiate the growth of copies of assemblies of the target shape. Since the lengths of the genomes for these constructions are proportional to the number of points in the target shape, we also present a replicator which utilizes hierarchical self-assembly to greatly reduce the size of the genomes required. The main goals of this work are to examine minimal requirements of self-assembling systems capable of self-replicating behavior, with the aim of better understanding self-replication in nature as well as understanding the complexity of mimicking it.

Serotonin Receptors in Myocardial Infarction: Friend or Foe?

Acute myocardial infarction (AMI) is one of the leading causes of death worldwide and treatment costs pose a major burden on the global health care system. Despite the variety of treatment options, individual recovery can be still poor and the mortality rate, especially in the first few years after the event, remains high. Therefore, intense research is currently focused on identifying novel target molecules to improve the outcome following AMI. One of the potentially interesting targets is the serotonergic system (5-HT system), not at least because of its connection to mental disorders. It is known that patients suffering from AMI have an increased risk of developing depression and vice versa. This implicates that the 5-HT system can be affected in response to AMI and might thus represent a target structure for patients' treatment. This review aims to highlight the importance of the 5-HT system after AMI by describing the role of individual serotonin receptors (5-HTR) in the regulation of physiological and pathophysiological responses. It particularly focuses on the signaling pathways of the serotonin receptors 1, 2, 4, and 7, which are expressed in the cardiovascular system, during disease onset, and the following remodeling process. This overview also emphasizes the importance of the 5-HT system in AMI etiology and highlights 5-HTRs as potential treatment targets.

The individual variability of the dentato-rubro-thalamic tract in the planning of stereotactic operations in patients with tremor

Background. Stereotactic operations on the ventral‑intermediate nucleus of the thalamus (Vim) and the posterior subthalamic area (PSA) are used for the surgical treatment of tremor. Since these structures are invisible in standard magnetic resonance imaging (MRI) regimes, indirect stereotactic guidance is mainly used during operations. MRI tractography allows taking into account the individual variability of the target structures for tremor, visualizing the target directly, but this technique has not yet entered the routine practice of preparing operations.Aim. The aim of the work is to study the variability of the position of the dentato‑rubro‑thalamic tract (DRT), determined according to MRI tractography data, in relation to the main reference points for indirect stereotactic guidance, as well as to the visible landmarks on MRI in FGATIR mode, to assess the validity of the currently used methods of preparing operations in patients with tremor.Materials and methods. Probabilistic MRI tractography of DRT based on the HARDY protocol was performed in 34 patients. Additionally, 3D T1 tomograms were obtained with axial slices with an isotropic voxel size equal to 1 mm, as well as FLAIR sagittal slices with a thickness of 1.12 and a pitch of 0.56 mm. Eleven patients additionally underwent a series of MRI sections according to the FGATIR program with a thickness of 1 mm, without an intersectional gap.Results. A significant variability of the DRT position has been established both in the coordinate system of the anterior and posterior commissures, and in relation to standard targets for indirect stereotactic guidance. In addition, a visible interhemispheric asymmetry of the position of the tracts was revealed. The smallest degree of deviation from the tract was noted for the trajectories of deep brain stimulation electrodes implanted in the caudal zona incerta (cZI) at the level of the maximum diameter of the red nuclei. A high degree of correspondence between the tract and the target zone of prelemniscal radiations (Raprl) was also established on tomograms in the FGATIR mode.Conclusions. The standard target points for the indirect targeting of Vim targets and the cerebello‑thalamic tract in PSA give a deviation of more than 2 mm from DRT in almost half of patients. During the use of cZI as a standard target for indirect guidance in the treatment of tremor, the DRT is located at the zone of stereotactic impact at the level of the 2nd or 3rd contact of the electrode in 76.5 % of cases. FGATIR mode allows visualizing the structure of Raprl, with stereotactic guidance on which the effect on the DRT can be achieved in 86.4 % of cases.

Identification of Serum Interleukin-22 as Novel Biomarker in Pulmonary Hypertension: A Translational Study.

Growing evidence suggests the crucial involvement of inflammation in the pathogenesis of pulmonary hypertension (PH). The current study analyzed the expression of interleukin (IL)-17a and IL-22 as potential biomarkers for PH in a preclinical rat model of PH as well as the serum levels in a PH patient collective. PH was induced by monocrotalin (60 mg/kg body weight s.c.) in 10 Sprague Dawley rats (PH) and compared to 6 sham-treated controls (CON) as well as 10 monocrotalin-induced, macitentan-treated rats (PH_MAC). Lung and cardiac tissues were subjected to histological and immunohistochemical analysis for the ILs, and their serum levels were quantified using ELISA. Serum IL levels were also measured in a PH patient cohort. IL-22 expression was significantly increased in the lungs of the PH and PH_MAC groups (p = 0.002), whereas increased IL17a expression was demonstrated only in the lungs and RV of the PH (p < 0.05) but not the PH_MAC group (p = n.s.). The PH group showed elevated serum concentrations for IL-22 (p = 0.04) and IL-17a (p = 0.008). Compared to the PH group, the PH_MAC group demonstrated a decrease in IL-22 (p = 0.021) but not IL17a (p = n.s.). In the PH patient collective (n = 92), increased serum levels of IL-22 but not IL-17a could be shown (p < 0.0001). This elevation remained significant across the different etiological groups (p < 0.05). Correlation analysis revealed multiple significant relations between IL-22 and various clinical, laboratory, functional and hemodynamic parameters. IL-22 could serve as a promising inflammatory biomarker of PH with potential value for initial diagnosis, functional classification or even prognosis estimation. Its validation in larger patients' cohorts regarding outcome and survival data, as well as the probability of promising therapeutic target structures, remains the object of further studies.

A comprehensive review of the recent advances on predicting drug-target affinity based on deep learning.

Accurate calculation of drug-target affinity (DTA) is crucial for various applications in the pharmaceutical industry, including drug screening, design, and repurposing. However, traditional machine learning methods for calculating DTA often lack accuracy, posing a significant challenge in accurately predicting DTA. Fortunately, deep learning has emerged as a promising approach in computational biology, leading to the development of various deep learning-based methods for DTA prediction. To support researchers in developing novel and highly precision methods, we have provided a comprehensive review of recent advances in predicting DTA using deep learning. We firstly conducted a statistical analysis of commonly used public datasets, providing essential information and introducing the used fields of these datasets. We further explored the common representations of sequences and structures of drugs and targets. These analyses served as the foundation for constructing DTA prediction methods based on deep learning. Next, we focused on explaining how deep learning models, such as Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), Transformer, and Graph Neural Networks (GNNs), were effectively employed in specific DTA prediction methods. We highlighted the unique advantages and applications of these models in the context of DTA prediction. Finally, we conducted a performance analysis of multiple state-of-the-art methods for predicting DTA based on deep learning. The comprehensive review aimed to help researchers understand the shortcomings and advantages of existing methods, and further develop high-precision DTA prediction tool to promote the development of drug discovery.

Off-site 3D printed concrete beam design and fabrication

This study identifies the need for a prefabricated reinforced 3D printed concrete (3DPC) beam that can integrate into a building system. A novel 3DPC beam for a specified target structure is designed, fabricated, and experimentally tested. The beam design is experimentally investigated by fabricating the beam with design-determined print parameters and performing a set of two large-scale 4-point bending tests which determine the shear and flexural resistance of the beam. Modified Eurocode design equations successfully predict the flexural resistance within 6%, however the shear design equations overpredict the shear resistance by 51%. The study provides a replicable design and fabrication workflow for 3DPC elements, and a feasible 3DPC beam concept that requires shear strengthening before application in the target frame. 3D concrete printing designers are provided with a 3DPC beam solution with the potential to integrate into a building system and are further equipped to design and fabricate future 3DPC building elements.