Module Assembly Research Articles

Identification of key genes in salivary gland in Sjögren's syndrome complicated with Hashimoto thyroiditis: Common pathogenesis and potential diagnostic markers.

The coexistence of Sjögren's syndrome (SS) and Hashimoto thyroiditis (HT) has been confirmed, but the common mechanism of its co-occurrence remains unknown. This study aims to further explore the underlying mechanism and biomarkers for the co-occurrence of SS and HT. The Gene Expression Omnibus databases were used to obtain gene expression profiles for SS (GSE127952 and GSE23117) and HT (GSE29315 and GSE138198). Following identifying SS and HT's shared differentially expressed genes, functional annotation, protein-protein interaction network creation, and module assembly were performed to discover hub genes. H&E staining and immunohistochemistry were performed to validate the expression of the hub genes in salivary glands. Finally, the receiver operating characteristic (ROC) curve was utilized to assess the discrimination of the hub genes as biomarkers in predicting SS, this study applied CIBERSORTx to analyze the immune infiltration in SS and HT in addition. A total of 48 common differentially expressed genes (48 upregulated genes and 0 downregulated genes) were chosen for further investigation. We analyzed the expression and function of PTPRC, CD69, IKZF1, and lymphocyte cytosolic protein 2 via H&E, immunohistochemistry, and ROC analysis. The 4 hub genes were mainly enriched in the T-cell receptor signaling pathway. We then evaluated and verified the diagnosis value of 4 hub genes in clinical minor labial gland biopsy of SS with HT, SS without HT, and non-SS. ROC analysis revealed that the 4 hub genes had a strong diagnostic value. Our study showed the common pathogenesis of SS and HT. These hub genes and diagnostic models may put forward some new insights for diagnosing and treating SS complicated with HT.

Dual-adaptive energy management strategy design for fast start-up and thermal balance control of multi-stack solid oxide fuel cell combined heat and power system

Solid oxide fuel cell (SOFC) hybrid system offers several advantages, including rapid start-up, effectively mitigating thermal stress and system stability. In this study, a multi-stack SOFC battery hybrid (SBH) Combined Heat and Power (CHP) system is designed. A dual-adaptive control strategy for this multi-stack system is proposed. The assembly of each power generation module (PGM) in parallel is implemented and the reliability of the system is verified. The dynamic characteristics of the multi-stack SBH-CHP system and the effect of temperature on the system are investigated. The results show that the multi-stack system can achieve stability within 80 s. The transient current observed in the system reaches up to 40 A, which accounts for at least 25% of the current generated by the SOFC. The system exhibits robust and prompt dynamic response characteristics, which ultimately contribute to an extended operational lifespan. The proposed adaptive control method and adaptive energy management strategy have been proven to be effective approaches for addressing the issues associated with rapid start-up and over-temperature within the multi-stack SBH-CHP system.

Novel non-HAP class A HBV capsid assembly modulators have distinct in vitro and in vivo profiles.

Chronic hepatitis B is the most important cause of liver cancer worldwide and affects more than 290 million people. Current treatments are mostly suppressive and rarely lead to a cure. Therefore, there is a need for novel and curative drugs that target the host or the causative agent, hepatitis B virus itself. Capsid assembly modulators are an interesting class of antiviral molecules that may one day become part of curative treatment regimens for chronic hepatitis B. Here we explore the characteristics of a particularly interesting subclass of capsid assembly modulators. These so-called non-HAP CAM-As have intriguing properties in cell culture but also clear virus-infected cells from the mouse liver in a gradual and sustained way. We believe they represent a considerable improvement over previously reported molecules and may one day be part of curative treatment combinations for chronic hepatitis B.

A novel hepatitis B virus capsid assembly modulator QL-007 inhibits HBV replication and infection through altering capsid assembly

The core protein allosteric modulators (CpAMs) have shown great potential as highly effective antiviral drugs against hepatitis B virus (HBV) in preclinical studies and clinical trials. In this study, we evaluated a small molecule compound called QL-007, which could potentially influence capsid assembly, using HBV replicated and susceptible cell models as well as mice infected with rAAV-HBV. QL-007 significantly inhibited HBV replication in a dose-dependent manner both in vitro and in vivo, resulting in significant decreases in HBV DNA, 3.5 kb HBV RNA and HBeAg. Furthermore, QL-007 not only induced the formation of misshaped Cp149 capsids but also possessed the capability to disassemble HBV capsids. It is noteworthy that QL-007 effectively reduced cccDNA biosynthesis in de novo infections. Mechanistically, QL-007 blocked the encapsidation of pgRNA and induced aberrant polymers assembly at concentrations ≥100 nM, while having no impact on the stability of core proteins. In conclusion, our findings underscore the potential of QL-007 as an effective agent against HBV replication and introduce it as a novel CpAM for the antiviral treatment of chronic hepatitis B.

Alternate Strategies to Induce Dynamically Modulated Transient Transcription Machineries.

Emulating native transient transcription machineries modulating temporal gene expression by synthetic circuits is a major challenge in the area of systems chemistry. Three different methods to operate transient transcription machineries and to modulate the gated transcription processes of target RNAs are introduced. One method involves the design of a reaction module consisting of transcription templates being triggered by promoter fuel strands transcribing target RNAs and in parallel generating functional DNAzymes in the transcription templates, modulating the dissipative depletion of the active templates and the transient operation of transcription circuits. The second approach involves the application of a reaction module consisting of two transcription templates being activated by a common fuel promoter strand. While one transcription template triggers the transcription of the target RNA, the second transcription template transcribes the anti-fuel strand, displacing the promoter strand associated with the transcription templates, leading to the depletion of the transcription templates and to the dynamic transient modulation of the transcription process. The third strategy involves the assembly of a reaction module consisting of a reaction template triggered by a fuel promoter strand transcribing the target RNA. The concomitant nickase-stimulated depletion of the promoter strand guides the transient modulation of the transcription process. Via integration of two parallel fuel-triggered transcription templates in the three transcription reaction modules and application of template-specific blocker units, the parallel and gated transiently modulated transcription of two different RNA aptamers is demonstrated. The nickase-stimulated transiently modulated transcription reaction module is applied as a functional circuit guiding the dynamic expression of gated, transiently operating, catalytic DNAzymes.

Pharmacophore-Based Virtual Screening and Structural Modification of Novel Benzamide Derivatives as HBV Capsid Assembly Modulators.

Hepatitis B virus (HBV) infection is the most common cause of death from liver disease worldwide. The use of capsid assembly modulators is considered a prominent strategy for the development of novel anti-HBV therapies. We performed a pharmacophore-based virtual screening strategy, and a benzamide scaffold hit, WAI-5, was chosen for further structural optimization. A series of novel HBV capsid assembly modulators (CAMs) were found. Compared with the lead hit, the representative compounds 11g and 11n exhibited a 10-fold increase in anti-HBV activity with 50% effective concentration (EC50) values of 1.74 and 1.90 µM, respectively.

Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure.

Hepatitis B virus (HBV) is a hepadnavirus, a small DNA virus that infects liver tissue, with some unusual replication steps that share similarities to retroviruses. HBV infection can lead to chronic hepatitis B (CHB), a life-long infection associated with significant risks of liver disease, especially if untreated. HBV is a significant global health problem, with hundreds of millions currently living with CHB. Currently approved strategies to prevent or inhibit HBV are highly effective, however, a cure for CHB has remained elusive. To achieve a cure, elimination of the functionally integrated HBV covalently closed chromosomal DNA (cccDNA) genome is required. The capsid core is an essential component of HBV replication, serving roles when establishing infection and in creating new virions. Over the last two and a half decades, significant efforts have been made to find and characterize antivirals that target the capsid, specifically the HBV core protein (Cp). The antivirals that interfere with the kinetics and morphology of the capsid, termed capsid assembly modulators (CAMs), are extremely potent, and clinical investigations indicate they are well tolerated and highly effective. Several CAMs offer the potential to cure CHB by decreasing the cccDNA pools. Here, we review the biology of the HBV capsid, focused on Cp, and the development of inhibitors that target it.

Microstructure Model to Predict Mechanical Behavior of Lithium-Ion Battery Active Material Under Compressive Load

A three-dimensional microstructure-based modeling method (3DMS) is developed to predict the mechanical behaviors of porous electrode that includes both active material (AM) and binders inside lithium-ion battery during compression. The geometry of both AM and binder shown in Fig. 1a is generated stochastically to create microstructures by using a modified MATBOX opensource program with our in-house code. The advanced technique of volume element generation is also established to overcome the interfacial error due to complexity of binder distribution as illustrated in Fig. 1b. The Finite Element Analysis (FEA) based solid-stress model is applied to predict local mechanical activities including stress-strain relationship and microstructure evolution.The predictions of anisotropic behavior in the porous electrode under compressive loads will be presented and the insights into the microstructure deformation will be discussed. Further, the analysis results will be validated using experimental testing results acquired at various length scales. This work can be used for the model-based FEA platform to predict the impact of volume change under charge/discharge cycles, volume change of a jelly-roll during formation, and the response of the active material in typical pouch cells during battery module assembly. Figure 1

Design, synthesis, and structure-activity relationship of a bicyclic HBV capsid assembly modulator chemotype leading to the identification of clinical candidate AB-506

Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development.

LEGO-like Assembly of Fibrous Modules for Display Textiles.

Due to their promising advantages over classical rigid devices, the development of display textiles has exciting potential for various fields, including sensor technology, healthcare, and communication. To realize display textiles, it is necessary to prepare light-emitting building blocks at the fiber level and then weave or knit them to form the desired textile structures. However, from a practical viewpoint, it is difficult to continuously weave functional fibers containing light-emitting devices using conventional textile technologies. To address this issue, we introduced fibrous modules that can be assembled like LEGO blocks to realize textile displays. A unique feature of this work is that the light-emitting pixels are generated through a simple contact between modular electrochemiluminescent (ECL) fibers. Each fiber is composed of a single metallic wire coated with a gel-type ECL electrolyte that is formed by using a simple dip-coating method in ambient air. The sticky nature of the gel electrolyte enables the construction of light-emitting pixels through the simple physical contact of two or more fiber modules without the need for external pressure or heating. The diversity of this technology offers in terms of fibrous module arrangements and assembly can provide various options for designing the geometries of light-emitting pixels. We have implemented this technique to demonstrate not only a 1 × 1 pixel but also 3 × 3 pixels with an irregular shape. These results demonstrate that the unique strategy for display devices developed in this work provides a feasible approach for various electronic and optical textile applications.

Initial lateral stiffness of plate-type modular steel frame structure with semi-rigid corner connections

The plate-type modular steel frame buildings with semi-rigid corner connections are assembled structures, whose prefabricated plate-type modules are constructed in the factory and assembled on site. Owing to the assembly of different plate-type modules, this self-bearing building forms a double-beam and multi-column structure. To calculate the initial lateral stiffness of the plate-type modular steel frame structure with semi-rigid corner connections, based on the modified displacement method, the lateral amplification effect caused by semi-rigid connections between upper and lower modules was transferred to the lower beam of the upper module; according to the concept of superposed beam, the structure can be simplified into the form of single beam and multiple columns; in addition, by using the combination method of multiple columns with different corner connections, the theoretical formulas of the initial lateral stiffness of the semi-rigid connected plate-type modular frame structure were derived. Compared with the plate-type modular frame with rigid connections, the lateral amplification coefficients of regular plate-type modular frames with semi-rigid connections were derived and the influence of the number of spans and stories on the lateral amplification coefficient were investigated. The theoretical values of the initial lateral stiffness of the plate-type modular steel frame with semi-rigid connections were in good agreement with the experimental values and FEM evaluations.

Size-Specific Modulation of a Multienzyme Glucosome Assembly during the Cell Cycle.

Enzymes in glucose metabolism have been subjected to numerous studies, revealing the importance of their biological roles during the cell cycle. However, due to the lack of viable experimental strategies for measuring enzymatic activities particularly in living human cells, it has been challenging to address whether their enzymatic activities and thus anticipated glucose flux are directly associated with cell cycle progression. It has remained largely elusive how human cells regulate glucose metabolism at a subcellular level to meet the metabolic demands during the cell cycle. Meanwhile, we have characterized that rate-determining enzymes in glucose metabolism are spatially organized into three different sizes of multienzyme metabolic assemblies, termed glucosomes, to regulate the glucose flux between energy metabolism and building block biosynthesis. In this work, we first determined using cell synchronization and flow cytometric techniques that enhanced green fluorescent protein-tagged phosphofructokinase is adequate as an intracellular biomarker to evaluate the state of glucose metabolism during the cell cycle. We then applied fluorescence single-cell imaging strategies and discovered that the percentage of Hs578T cells showing small-sized glucosomes is drastically changed during the cell cycle, whereas the percentage of cells with medium-sized glucosomes is significantly elevated only in the G1 phase, but the percentage of cells showing large-sized glucosomes is barely or minimally altered along the cell cycle. Should we consider our previous localization-function studies that showed assembly size-dependent metabolic roles of glucosomes, this work strongly suggests that glucosome sizes are modulated during the cell cycle to regulate glucose flux between glycolysis and building block biosynthesis. Therefore, we propose the size-specific modulation of glucosomes as a behind-the-scenes mechanism that may explain functional association of glucose metabolism with the cell cycle and, thereby, their metabolic significance in human cell biology.

Improvement of silicon heterojunction module efficiency using fast illumination post-treatments

Intense illumination treatments on silicon heterojunction cells (SHJ) have recently gained interest to improve the final cell efficiency and are now being implemented into cell manufacturing tools. However, additional efforts are still required to clarify the robustness of such approach. Indeed, it has been reported that the positive effects of the intense illumination treatments applied to cells may be partly lost during module assembly. Therefore, in order to circumvent these potential issues, we reveal herein a broad investigation on the interest of intense illumination treatments directly at module level, using an experimental lab tool provided by Applied Materials, Baccini (Italy). Efficiency gains up to +0.3 %abs have been achieved within a treatment process time compatible with industry requirements. The gains remained stable for two months after a slight decrease during the first days (−0.05 %abs). Moreover, the reliability tests against UV, thermal cycling and damp heat did not reveal any detrimental influence of the post-treatments applied to the modules, further highlighting the fast illumination post-treatment as promising candidate for the next generation of high technologically advanced photovoltaic modules manufacturing production lines.

Quality Assurance Test System for Assembly of STS Modules for the BM@N Experiment

The Silicon Tracking System (STS) of the BM@N experiment will be based on modules with Double-Sided microstrip Silicon Detectors (DSSD) which have been initially developed for the CBM experiment at FAIR. Each module consists of a DSSD, two front-end boards with 8 ASICs each, and a set of low-mass aluminum microcables. During the module assembly the microcables are tab-bonded to the sensor and readout ASICs. The module has 1024 channels on each side of the sensor. For the quality assurance of the ultrasonic bonding process a dedicated procedure based on the noise per channel measurements with a Pogo Pin test device was developed.

Prefabricated buildings made of block modules with nonremovable formwork

Introduction. The construction technology of prefabricated buildings, along with the high quality of construction, is widely used for all types of buildings and structures.Aim. To maximize the safety of people and equipment after impact. This is achieved by:1) development of a design solution for a thin-walled plate-membrane capable of obtaining significant deflections without collapse;2) technologies for assembling spatial block modules made of membrane plates without welding;3) working out technological issues of manufacturing plates-membranes; assembly of block modules; sealing joints between block modules.Materials and methods. In the manufacture of membrane plates, fine-grained concrete of the VSM B25 P2 F200 W4 brand was used with the use of a fine additive (barite), spiral reinforcement of spring wire d = 1.6 mm.Results. The proposed design solution has significant reserves of strength and deformability. This ensures the safety of people and equipment.Conclusions. The use of spiral reinforcement makes it possible to manufacture thin-walled structures with the further construction of block modules with them and, after filling with light concrete, to obtain prefabricated buildings and structures that can withstand significant loads by external shock forces.

Experimental and numerical study on energy harvesting performance thermoelectric generator applied to a screw compressor

Abstract In this paper, an experimental and numerical investigation of thermoelectric generator for energy harvesting performance of screw compressors has been studied. The sources of heat recovery from compressors are recognized and a heat exchanger to mount the Thermoelectric Generator (TEG) module assembly is designed to adapt for implementation in this work. Computational fluid dynamics (CFD) is used to find out the temperature distribution in the heat exchanger and experimental work is carried out to validate CFD results. The heat exchangers, consisting of five TEG modules, temperature profile and voltage value have been studied numerically and experimentally. The parametric study has been studied to understand the influence of various system parameters on energy harvesting performance TEG based heat exchanger. An average of 1.6 V is generated by each TEG module and heat exchanger consists of five TEG and an average of 8 V is generated continuously by the heat exchanger. Also, it is proved that the usages of steel foam with 90 % porosity in heat exchanger improves the heat transfer rate and maximize the output from 8 V to 24 V in heat exchanger.

Structure-based Design of Novel Hepatitis B Virus Capsid Assembly Modulators

Small-molecule capsid assembly modulators (CAMs) have been recently recognized as promising antiviral agents for curing chronic hepatitis B virus (HBV) infection. A target-based in silico screening study is described, aimed towards the discovery of novel HBV CAMs. Initial optimization of four weakly active screening hits was performed via focused library synthesis. Lead compound 42 and close analogues 56 and 57 exhibited in vitro potency in the sub- and micromolar range along with good physico-chemical properties and were further evaluated in molecular docking and mechanism of action studies.

Exploring Giant Unilamellar Vesicle Production for Artificial Cells - Current Challenges and Future Directions.

Creating an artificial cell from the bottom up is a long-standing challenge and, while significant progress has been made, the full realization of this goal remains elusive. Arguably, one of the biggest hurdles that researchers are facing now is the assembly of different modules of cell function inside a single container. Giant unilamellar vesicles (GUVs) have emerged as a suitable container with many methods available for their production. Well-studied swelling-based methods offer a wide range of lipid compositions but at the expense of limited encapsulation efficiency. Emulsion-based methods, on the other hand, excel at encapsulation but are only effective with a limited set of membrane compositions and may entrap residual additives in the lipid bilayer. Since the ultimate artificial cell will need to comply with both specific membrane and encapsulation requirements, there is still no one-method-fits-all solution for GUV formation available today. This review discusses the state of the art in different GUV production methods and their compatibility with GUV requirements and operational requirements such as reproducibility and ease of use. It concludes by identifying the most pressing issues and proposes potential avenues for future research to bring us one step closer to turning artificial cells into a reality.

Structure and assembly of the NOT10:11 module of the CCR4-NOT complex

NOT1, NOT10, and NOT11 form a conserved module in the CCR4-NOT complex, critical for post-transcriptional regulation in eukaryotes, but how this module contributes to the functions of the CCR4-NOT remains poorly understood. Here, we present cryo-EM structures of human and chicken NOT1:NOT10:NOT11 ternary complexes to sub-3 Å resolution, revealing an evolutionarily conserved, flexible structure. Through biochemical dissection studies, which include the Drosophila orthologs, we show that the module assembly is hierarchical, with NOT11 binding to NOT10, which then organizes it for binding to NOT1. A short proline-rich motif in NOT11 stabilizes the entire module assembly.

Identification of novel tetrahydroquinoxaline derived phenyl ureas as modulators of the hepatitis B virus nucleocapsid assembly

A key step of hepatitis B virus (HBV) replication is the selective packaging of pregenomic RNA (pgRNA) by core protein (Cp) dimers, forming a nucleocapsid where the reverse transcriptional viral DNA replication takes place. One approach in the development of new anti-HBV drugs is to disrupt the assembly of HBV nucleocapsids by misdirecting Cp dimers to assemble morphologically normal capsids devoid of pgRNA. In this study, we built upon our previous discovery of benzamide-derived HBV capsid assembly modulators by exploring fused bicyclic scaffolds with an exocyclic amide that is β, γ to the fused ring, and identified 1,2,3,4-tetrahydroquinoxaline derived phenyl ureas as a novel scaffold. Structure-activity relationship studies showed that a favorable hydrophobic substitution can be tolerated at the 2-position of the 1,2,3,4-tetrahydroquinoxaline core, and the resulting compound 88 demonstrated comparable or improved antiviral potencies in mouse and human hepatocyte-derived HBV-replicating cell lines compared to our previously reported benzamide compound, 38017 (8). In addition, a novel bis-urea series based on 1,2,3,4-tetrahydroquinoxaline was also found to inhibit HBV DNA replication with sub-micromolar EC50 values. The mode of action of these compounds is consistent with specific inhibition of pgRNA encapsidation into nucleocapsids in hepatocytes.