Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

The cardiac sodium ion channel (NaV1.5) is a protein with four domains (DI-DIV), each with six transmembrane segments. Its opening and subsequent inactivation results in the brief rapid influx of Na+ ions resulting in the depolarization of cardiomyocytes. The neurotoxin veratridine (VTD) inhibits NaV1.5 inactivation resulting in longer channel opening times, and potentially fatal action potential prolongation. VTD is predicted to bind at the channel pore, but alternative binding sites have not been ruled out. To determine the binding site of VTD on NaV1.5, we performed docking calculations and high-throughput electrophysiology experiments. The docking calculations identified two distinct binding regions. The first site was in the pore, close to the binding site of NaV1.4 and NaV1.5 blocking drugs in experimental structures. The second site was at the “mouth” of the pore at the cytosolic side, partly solvent-exposed. Mutations at this site (L409, E417, and I1466) had large effects on VTD binding, while residues deeper in the pore had no effect, consistent with VTD binding at the mouth site. Overall, our results suggest a VTD binding site close to the cytoplasmic mouth of the channel pore. Binding at this alternative site might indicate an allosteric inactivation mechanism for VTD at NaV1.5.

KV channel-interacting proteins (KChIPs) belong to a family of Ca2+-binding EF-hand proteins that are able to bind to the N-terminus of the KV4 channel α-subunits. As the auxiliary subunit, KChIPs are critically involved in regulating the amplitude and gating properties of KV4 channels by modulating their cell surface trafficking, voltage-dependent activation, inactivation kinetics, and recovery rate from inactivation. IKs, ICa,L, and INa can also be regulated by KChIPs. KChIPs are predominantly expressed in the brain and heart, where they contribute to the maintenance of the excitability of neurons and cardiomyocytes by modulating the KV4 currents. Interestingly, all KChIPs can act as transcription factors to control the expression of genes involved in pain, memory, and circadian regulation. Altered expression of KChIPs has been implicated in the pathogenesis of many diseases, such as arrhythmia, heart failure, Alzheimer's disease, etc. In this review, we summarize the research progress of KChIPs in their structural properties, physiological functions, and pathological roles in disease progression, and provide an overview of the therapeutic potential of KChIPs as pharmacological targets for associated disorders.

Semisolid casting can provide excellent castings, but the nature of the pore-forming mechanisms has not been properly clarified. In the current communication, it was suggested that hydrogen precipitated during slurry making might have a decisive role in the formation of both gas and shrinkage porosity. Intensive stirring at the end of the slurry making process may act as a degassing step. Without the intense stirring, structures of primary slurry particles form around the hydrogen pores, strongly affecting pore formation and feeding during the intensification stage.

We aimed to investigate the relationship between membrane material and development of membrane fouling in a membrane bioreactor (MBR) using membranes with different pore sizes and hydrophilicities. Batch filtration tests were performed using submerged single hollow fiber membrane ultrafiltration (UF) modules with different polymeric membrane materials including cellulose acetate (CA), polyethersulfone (PES), and polyvinylidene fluoride (PVDF) with activated sludge taken from a municipal wastewater treatment plant. The three UF hollow fiber membranes were prepared by a non-solvent-induced phase separation method and had similar water permeabilities and pore sizes. The results revealed that transmembrane pressure (TMP) increased more sharply for the hydrophobic PVDF membrane than for the hydrophilic CA membrane in batch filtration tests, even when membranes with similar permeabilities and pore sizes were used. PVDF hollow fiber membranes with smaller pores had greater fouling propensity than those with larger pores. In contrast, CA hollow fiber membranes showed good mitigation of membrane fouling regardless of pore size. The results obtained in this study suggest that the surface hydrophilicity and pore size of UF membranes clearly affect the fouling properties in MBR operation when using activated sludge.

The human mandible's cancellous bone, which is characterized by its unique porosity and directional sensitivity to external forces, is crucial for sustaining biting stress. Traditional CAD models fail to fully represent bone's anisotropic structure and thus depend on simple isotropic assumptions. For our research, we use the latest versions of nTopology and Creo Parametric software to make biomimetic Voronoi lattice models that accurately reflect the complex geometry and mechanical properties of trabecular bone. The porosity of human cancellous bone is accurately modeled in this work using biomimetic Voronoi lattice models. The porosities range from 70% to 95%, which can be achieved by changing the pore sizes to 1.0 mm, 1.5 mm, 2.0 mm, and 2.5 mm. Finite element analysis (FEA) was used to examine the displacements, stresses, and strains acting on dental implants with a buttress thread, abutment, retaining screw, and biting load surface. The results show that the Voronoi model accurately depicts the complex anatomy of the trabecular bone in the human jaw, compared to standard solid block models. The ideal pore size for biomimetic Voronoi lattice trabecular bone models is 2 mm, taking into account both the von Mises stress distribution over the dental implant, screw retention, cortical bone, cancellous bone, and micromotions. This pore size displayed balanced performance by successfully matching natural bone's mechanical characteristics. Advanced finite element analysis (FEA) improves biomechanical understanding of how bones and implants interact by creating more accurate models of biological problems and dynamic loading situations. This makes biomechanical engineering better.

Dynamic systems which underly controlled systems are expected to increase in complexity as robots, devices, and connected networks become more intelligent. While classical stable systems converge to a stable point (a sink), another type of stability is to consider a stable path rather than a single point. Such stable paths can be made of saddles which draw in trajectories from certain regions, and then push the trajectory toward the next saddle point. These are chains of saddles are called stable heteroclinic channels (SHCs), and can be used in robotic control to represent time sequences. While we have previously shown that each saddle is visualizable as a trajectory waypoint in phase space, how to increase the fidelity of the trajectory was unclear. In this paper, we hypothesized that the waypoints can be individually modified to locally vary fidelity. Specifically, we expected that increasing the saddle value (ratio of saddle eigenvalues) causes the trajectory to slow to more closely approach a particular saddle. Combined with other parameters that control speed and magnitude, a system expressed with an SHC can be modified locally, point by point, without disrupting the rest of the path, supporting their use in motion primitives. However, even more complex trajectory shape modifications are possible. While some combinations can enable a trajectory to better reach into corners, other combinations can rotate, distort and round the trajectory in the region of a corner. In our example, modifying select saddle values produced a 32% decrease in the trajectory error of a complex trajectory produced using this system. This is an effect not visible in previous 1D studies, that can lead to different learnable and tunable representations of dynamic systems.

Channel bends are one of the most important characteristic features of natural streams. These bends often create the conditions for a hyporheic zone, which has been recognized as a critical component of stream ecosystems. The streambed vertical hydraulic conductivity (K_v), vertical hydraulic gradient (VHG) and Darcian flux (DF) in the hyporheic zone were estimated at 61 locations along a channel bend of the Beiluo River during July 2015 and January 2016. All the streambed attributes showed great spatial variability along the channel bend. Both upward fluxes and downward fluxes occurred during the two test periods, most of studied stream sections were controlled by downwelling, indicating stream water discharge into the subsurface. The average downward flux was higher at the downstream side than at the upstream side of the channel bend, especially in July 2015. The distribution of streambed sediment grain size has a significant influence on the variability of K_v; high percentages of silt and clay sediments generally lead to low K_v values. Higher K_v at the depositional left bank at the upstream site shifted toward the erosional right bank at the downstream site, with K_v values positively correlated with the water depth. This study suggested that the variabilities of K_v and VHG were influenced by the stream geomorphology and that the distribution of K_v was inversely related, to a certain extent, to the distribution of VHG across the channel bend. K_v and VHG were found to have opposite effects on the DF, and the close relationship between K_v and DF indicated that the water fluxes were mainly controlled by K_v.

Dynamic optical structural color is always desired in various display applications and usually involves active materials. Full-color generation, especially bi-directional full-color generation in both reflective and transmissive modes, without any active materials included has been rarely investigated. Herein, we demonstrate a scheme of bi-directional full-color generation based on a plasmonic metasurface modulated by rotation of the polarization angle of the incident light without varying the geometry and the optical properties of the materials and the environment where the metasurface resides. The metasurface unit cell consists of plasmonic modules aligning in three directions and is patterned in a square array. The metasurface structural color device generates full colors in both reflection and transmission. Based on the proposed polarization-dependent structural color, information encoding of three multiplexed animal images and quick-responsive (QR) codes is demonstrated to verify the efficient information encoding and decoding of the proposed scheme. The animals can be seen under different polarization incidence and the QR codes can be successfully decoded by the polarization rotation in transmission. The proposed bi-directional full-color generation metasurface has great potential in applications such as kaleidoscope generation, anti-counterfeiting, dynamic color display, and optical information encoding.

Ion channels are integral membrane proteins that facilitate the movement of ions across cell membranes, playing a key role in a range of biological processes. The high cost and time required for wet lab experiments to characterize ion channels has spurred the development of computational methods for this purpose. In our previous work, we demonstrated the effectiveness of protein language models for ion channel prediction, using a logistic regression classifier to distinguish ion channels from non-ion channels (TooT-BERT-C) and transporters from non-transporters (TooT-BERT-T). In this study, we build upon this approach by using a combination of classical machine learning classifiers and a Convolutional Neural Network (CNN) with fine-tuned representations from ProtBERT, ProtBERT-BFD, and MembraneBERT to discriminate ion channels from non-ion channels. The results of our experiments demonstrate that TooT-BERT-CNN-C, a combination of the representations from ProtBERT-BFD and a CNN, outperforms existing state-of-the-art methods for predicting ion channels, with a Matthews Correlation Coefficient (MCC) of 0.86 and an accuracy of 98.35% on an independent test set.

An accurate assessment of the stage-discharge relationship in open channel flows is necessary and important to the design and management of hydraulic structures and engineering in practical hydrosystems such as rivers and streams. While the flow structures and patterns at open channel junctions are interesting and have been widely studied in the literature, this paper focuses further on the effect of flow junctions on stage-discharge relationship at mountain river confluences. In this study, both the flume and physical model experiments are designed and performed carefully to test and analyze the complex flow structures and characteristics at river confluences with different configurations and hydraulic conditions. The impacts of the flow junctions on the traditional stage-discharge relationship are analyzed in this study. The results of this study are discussed in the paper for the understanding of flow structures at flow junctions and the design and management of hydraulic structures in river engineering.

Finding a good MIMO system model also major issue in Wireless Communication system. It is facing with so many problem, one of the major problem is finding good system model in terms of capacity and transmitting antenna system. In this paper, we analyze the channel capacity of various MIMO system model with some constant SNR level and outage probability. We establish a novel idea for MIMO system models as consider as 2^N- MIMO system model and find-out change in channel capacity when different transmitting antennas with constant SNR and outage probability. The channel capacity ratio CC_R is presented here on the basis of 2^N- MIMO channel capacity model. Number of transmitted antenna presented in MIMO system is increases is well-known however paper shows change in capacity in simple form.

The cross-kingdom stress hormone abscisic acid (ABA) and its mammalian receptors LANCL1 and LANCL2 regulate cardiomyocyte response to hypoxia by activating NO generation. Over-expression of LANCL1/2 increases transcription, phosphorylation and activity of eNOS and im-proves cell vitality after hypoxia/reoxygenation via the AMPK/PGC-1α axis. The aim of this study was to investigate whether the ABA/LANCL system also affects mitochondrial oxidative metab-olism and structural proteins. The effect of ABA and of the silencing or overexpression of LANCL1 and LANCL2 were investigated in H9c2 rat cardiomyoblasts on mitochondrial function, cell cycle and expression of cytoskeletal, contractile and ion channel proteins. Overexpression or silencing of LANCL1/2 significantly increased, or conversely decreased, mitochondrial number, oxphos complex I, proton gradient, glucose and palmitate-dependent respiration, transcription of uncoupling proteins, expression of proteins involved in cytoskeletal, contractile and electrical functions. These effects, and LANCL1/2-dependent NO generation, are mediated by the tran-scription factor ERRα, upstream of the AMPK/PGC1-α axis and transcriptionally controlled by the LANCL1/2-ABA system. The ABA-LANCL1/2 hormone-receptors system controls fundamental aspects of cardiomyocyte physiology via an ERRα/AMPK/PGC-1α signaling axis and ABA-mediated targeting of this axis could improve cardiac function and resilience to hypoxic and dysmetabolic conditions.

Rheumatoid arthritis (RA) is a chronic inflammatory disease. Despite new methods of diagnostics and treatment as well as extensive biological and immunosuppressive treatment, the etiology of RA is not fully understood. Moreover, the problem of diagnosis and treatment of RA patients is still current and affects a large group of patients. It is suggested that these ER-related features may impair adaptation to chronic stress, inferring the risk of rheumatoid arthritis. The main goal in this study was evaluation of changes in mRNA translation to determine chronic ER stress conditions in rheumatoid arthritis patients. The study group consist of 86 individuals including total 56 rheumatoid arthritis patients and 30 healthy controls. The expression level of mRNA form blood samples of RA patients as well as controls of the PERK-UPR associated genes: p-eIF2, BCL-2, PERK, ATF4, BAX were investigated by Real-Time qPCR. GAPDH expression was used as a standard control. Considering the median, the expression of PERK, BCL-2, p-eIF2, ATF4, BAX was found to be significantly increased in the blood of RA patients compared with the control group. The p-value for the PERK gene was 0.0000000036, the p-value for the BCL-2 gene was 0.000000014, the p-value for the p-eIF2 gene was 0.006948, the p-value for the ATF4 gene was 0.0000056 and the p-value for the BAX gene was 0.00019, respectively. Thus, it can be concluded that targeting of the components of the PERK-dependent UPR signaling pathway via small-molecule PERK inhibitors, may contribute to the development of novel, innovative treatment strategies against rheumatoid arthritis.

Hemoconcentration membranes used in cardiopulmonary bypass require a pore structure design with high pure water permeability, and which does not allow protein adsorption and useful protein loss. However, studies on hemoconcentration membranes have not been conducted yet. The purpose of this study was to analyze three-dimensional pore structures and protein fouling before and after blood contact with capillary membranes using the tortuous pore diffusion model and a scanning probe microscope system. We examined two commercially available capillary membranes of similar polymer composition that are successfully used in hemoconcentration clinically. Assuming the conditions of actual use in cardiopulmonary bypass, we perfused these membranes with bovine blood. Pure water permeability before and after bovine blood perfusion was measured using the dead-end filtration. The scanning probe microscopy system was used for analysis. High-resolution three-dimensional pore structures on the inner surface of the membranes were observed before blood contact. On the other hand, pore structures after blood contact could not be observed due to protein fouling. The pore diameters calculated by the tortuous pore diffusion model and scanning probe microscopy were mostly similar and could be validated reciprocally. Achievable pure water permeabilities showed no difference despite protein fouling, leading to low values of albumin SC. This is due to the mechanism that protein fouling occurs on the membrane surface, while there is little internal pore blocking. Therefore, controlling the fouling is essential for membranes in medical use. These characteristics of the hemoconcentration membranes examined in this study are suitable for clinical use.

The initial valves of two Cymbella species are observed under the scanning electron microscope and the perizonium ultrastructure of Cymbella is revealed for the first time. The perizonium is composed of alternate nodes and internodes and lacks transverse perizonium bands. Four new species, Cymbella apiculatophora sp. nov., C. hunanensis sp. nov., C. juglandis sp. nov. and C. menyuanensis sp. nov., are described using light and scanning electron microscope from epilithon samples collected in rivers from Hunan and Qinghai Provinces, China. Cymbella menyuanensis is a typical Cymbella species that closely resembles species in the group around C. cymbiformis Agardh, the lectotype species of the genus. Cymbella apiculatophora is similar to C. sinensis Metzeltin & Krammer while Cymbella hunanensis is closer to the C. hustedtii Krasske group. The last species, C. juglandis, has a cymbelloid valve outline, obscured intermissio, internal occlusions of areolae, dorsally deflected distal raphe fissures, and a divided APF at each apex, and does not appear to belong to any group. In addition, new observations on C. cf. excisiformis Krammer and C. hustedtii are reported. The current concept of the genus Cymbella does not represent a monophyletic group as shown by molecular phylogenetic analyses. However, these analyses are still at the preliminary stage and are not yet sufficient to support a complete revision of the genus. Thus, although extremely diverse ultrastructural features are observed in the six Cymbella species investigated in this paper, we prefer to keep them within Cymbella at this moment for the sake of nomenclatural stability.

Wireless Powered Communication Networks (WPCN), which has attracted much attention of researchers, also been recently recommended in 5^th generation (5G) wireless networks. With the help of the WPCN, the reliability and battery life of wireless low-power devices can be improved. In this paper, we investigate throughput and ergodic capacity in WPCN-assisted amplify-and-forward (AF) relaying system, considering two transmission modes including delay-tolerant and delay-limited. As important achievement, we propose symmetric energy harvesting protocol, namely time power switching relaying (TPSR) in order to find maximal throughput. In particular, both time switching and power switching coefficients in this schemes are considered. Unlike most of the previous works, we further focus on impact of outdated channel state information (CSI) in this WPCN. In order to evaluate information processing efficiency, the performance can be substantially improved by optimally harvesting time and power coefficients of the received signal at relay node for energy and information extraction, and by deploying several scenarios. By deploying Monte Carlo simulation, it is confirmed that the system performance is more sensitive to CSI estimation error, noise variance, signal-to-noise ratio (SNR) and resulting in other reasonable computations of TPSR need be deployed to obtain QoS requirement.

Hypertension is a frequent risk factor for cardiovascular diseases and the prevalence rate is continuously rising. Multiple pathophysiological mechanisms are responsible for hypertension, necessitating a combination of drugs from different classes for best management. Combination therapy is five times more effective in decreasing blood pressure compared to escalating the dose of a single agent. As per the ACCOMPLISH trial analysis, coupling a renin-angiotensin system inhibitor with a calcium channel blocker is more effective than the combination of a renin-angiotensin system inhibitor with diuretics in reducing major cardiovascular events, cardiovascular-related mortality, and the progression of chronic kidney disease. The renin-angiotensin system can be suppressed by inhibiting the angiotensin-converting enzyme or angiotensin type 1 receptor (AT1R), resulting, in decreased vascular smooth muscle contraction, heart performance, and reduced aldosterone synthesis. Calcium channel blockers work by inhibiting L-type calcium channels, reducing heart performance via negative inotropic, chronotropic, and bathmotropic effects, along with reducing vascular smooth muscle contraction. Diuretics exert their antihypertensive impact by changing body fluid volume and electrolytes. Initially, hypertension treatment commences with a single medication but often, different classes of two or more antihypertensive medications are necessary for achieving the target blood pressure goal. Sometimes, for Resistant hypertension four different classes of antihypertensive medications are necessary to reach the target blood pressure goal.

In this study, literature on pore structure and chloride ion diffusivity was collected to investigate the correlation of pore structure indicators with diffusivity. Good correlation between total porosity and chloride ion diffusivity was found when the samples did not contain admixture materials and diffusion test was conducted without acceleration. Pore diameter indicators did not correlate with diffusivity. The diffusivity of cement paste was reduced by admixture materials compared to that without admixture materials even if the total porosity is the same. On the other hand, the diffusivity of concrete was not reduced by admixture materials.

The BET family of proteins is characterized by the presence of two tandem bromodomains and an extra-terminal domain. The mammalian BET family of proteins comprises Brd2, Brd3, Brd4, and Brdt, which are encoded by paralogous genes that may have been generated by repeated duplication of an ancestral gene during evolution. Bromodomains that can specifically bind acetylated lysine residues in histones serve as chromatin-targeting modules that decipher the histone acetylation code. BET proteins play a crucial role in regulating gene transcription through epigenetic interactions between bromodomains and acetylated histones during cellular proliferation and differentiation processes. On the other hand, BET proteins have been reported to mediate latent viral infection in host cells and be involved in oncogenesis. Human BRD4 is involved in multiple processes of the DNA virus life cycle, including viral replication, genome maintenance, and gene transcription through interaction with viral proteins. Aberrant BRD4 expression contributes to carcinogenesis by mediating hyperacetylation of the chromatin containing the cell proliferation-promoting genes. BET bromodomain blockade using small-molecule inhibitors gives rise to selective repression of the transcriptional network driven by c-Myc. These inhibitors are expected to be potential therapeutic drugs for a wide range of cancers. This review presents an overview of the basic roles of BET proteins and highlights the pathological functions of BET and the recent developments in cancer therapy targeting BET proteins in animal models.

Abstract: A. baumannii exhibits resilience in harsh environments and progressively develops resistance to diverse antibacterial agents over time. This adaptability poses a significant challenge in treating an infection caused by this bacterium within healthcare settings. The presence of peptidoglycan, a crucial precursor for cell wall synthesis, contributes to this challenge. Peptidoglycan serves not only as a structural support in bacterial cells but also provides protection against adverse environmental conditions. The synthesis of the peptidoglycan layer involves a group of substrates such as N-acetylglucosamine (GlcNAc) and N-acetylmuramic acid (MurNAc), within a three-partitioned process occurring in the membrane, periplasmic space, and cytoplasm of each bacterium. Initiated in the cytoplasm and extending to the inner cell membrane, this synthesis starts with the production of nucleotide precursors. The first step involves the synthesis of UDP-GlcNAc, orchestrated by Glm (GlmS, GlmM, and GlmU) enzymes using fructose-6-phosphate. Subsequently, enzymes from the Mur family, namely MurB, MurA, MurD, MurC, MurI, MurF, and MurE, synthesize UDP-N-acetylmuramyl-pentapeptide (UDP-Mpp) from UDP-GlcNAc. Concurrently, on the cytosolic side, the production of membrane-surrounded undecaprenyl phosphate occurs, involving membrane-side proteins MraY and MurG in the biosynthesis of peptidoglycan. This review emphasizes updated information on Mur family proteins, encompassing physicochemical properties, nature of binding site, number and type of binding site residues, functional domain details, three-dimensional structural aspects, and their functions within bacterial cells. Special attention is directed towards their enzymatic role in peptidoglycan biosynthesis due to the limited availability of precursors in the market. Additionally, the review provides a comprehensive summary of existing inhibitors and ongoing efforts in identifying new targeted inhibitors, recognizing these enzymes as potential candidates for antibacterial drug design and discovery.

Correlations between the air permeability coefficient and various pore structure indicators in cementitious materials were examined to determine the pore structure indicator that best evaluated air permeability using data from previous studies of air permeabilities and pore structures. The determination coefficients of air permeability with total pore volume, critical pore diameter, and ordinary threshold pore diameter were low, although these have often been used as indicators. The median and threshold pore diameters obtained by percolation theory showed high determination coefficients. The equation using the threshold pore diameter better estimated the air permeability coefficient than the Katz–Thompson equation.

To understand the relationship between water permeability and the pore structure of cementitious materials, literature that studied both water permeability and the pore structure are reviewed, and their correlation is studied. Although the majority of this data is for cement paste, mortar, concrete, and cemented soil are also included. Based on this study, it is established the determination coefficient between water permeability and the total pore volume is very low; however, those between water permeability and the critical, threshold, and median pore diameters, respectively, are moderate. On the other hand, the threshold pore diameter, derived based on the percolation theory, exhibits a very high determination coefficient. The calculated water permeability, using the Katz and Thompson equation, agrees with the reported water permeability quantitatively to a certain level, but is overestimated.

Intrinsically Disordered Proteins (IDPs) play crucial roles in signal transduction, cell differentiation, and transcriptional regulation. Many disrupted genes associated with mental disorders are identified as IDPs, and emerging evidence suggests the functional role of IDPs in neuropsychiatric disorders. However, few studies comprehensively explore the functional association between protein disorder properties and different mental diseases. To address this gap, we collected disrupted gene sets for seven mental diseases (MDD, SCZ, BP, ID, AD, ADHD, ASD) and a control gene set from normal brains using DisGeNET and GeneCards databases. The state-of-the-art predictor IUPred2A was then utilized to calculate the disorder properties , followed by a thorough comparison between the disordered proteins in mental diseases and healthy controls. Functional enrichment analysis and protein-protein interaction networks were conducted to investigate the IDPs’ functional roles in psychiatric diseases. Additionally, we demonstrated the role of IDPs in protein binding formations through a case study of alpha-synuclein using protein docking. Our findings reveal that differentially expressed proteins in mental disorders, especially in ASD and ADHD, exhibit more IDPs than those in healthy controls. IDPs in psychiatric disorders are significantly enriched in neurodevelopmental pathways and play an important role in in gene expression regulation. Our results indicate distinct functional patterns of disorder proteins among mental diseases and healthy controls. When comparing the IDPs between ASD and ADHD, we observed that IDPs in ADHD are more likely linked to the synaptic signaling and regulation, while IDPs in ASD are more tendentiously related to diverse and complex biological processes. Our work offers valuable insights into the important functions of IDPs in psychiatric disorders, enhancing our understanding of the molecular mechanisms involved in psychiatric disorders.

Proteins possess complex three-dimensional structures, and these structures are stable only within specific ranges of temperature which mostly correspond to the temperature ranges of the host organisms. However, few exceptional proteins, called heat-stable proteins, are stable at temperatures that are substantially higher than those tolerated by the host organisms themselves. Most of the heat-stable proteins possess heat stability to perform their functions at high temperatures, but some of them are intrinsically heat-stable due to their structure. Heat-stable proteins are usually divided into three or four groups depending upon the intricacies of their structures and thermal behaviors. Their peculiar property, i.e. heat-stability, makes them very valuable in applications such as polymerase chain reaction, industrial processes requiring high temperature, and protein engineering. Heat-stability also makes it feasible to purify such proteins, from the rest of the heat-labile proteins, using a simple heat-treatment method. Moreover, heat treatment can be used as a combined cell-lysis and protein purification step which, as compared to conventional methods, can result in a higher yield of heat-stable proteins. Furthermore, some special heat-stable proteins, i.e. intrinsically disordered proteins (which include the proteins involved in important neurodegenerative diseases), need heat-treatment step, in some cases, as the only way for their successful purification and study. Hence, this paper provides a first-ever comprehensive review of all major aspects of heat-stable proteins, i.e., their structure, evolution, classification, significance, and heat-treatment mediated purification.

The Zika virus (ZIKV) is a mosquito-borne Flavivirus and can be transmitted through an infected mosquito bite or through human-to-human interaction by sexual activity, blood transfusion, breastfeeding or perinatal exposure. After the 2015-2016 outbreak in Brazil, a strong link between ZIKV infection and microcephaly emerged. ZIKV specifically targets human neural progenitor cells, suggesting that proteins encoded by ZIKV bind and inactivate host cell proteins leading to microcephaly. Here, we present a systematic annotation of interactions between human proteins and the seven non-structural ZIKV proteins corresponding to a Brazilian isolate. The interaction network was generated by combining tandem-affinity purification followed by mass spectrometry with yeast two-hybrid screens. We identified 150 human proteins, involved in distinct biological processes, as interactors to ZIKV non-structural proteins. Our interacting network is composed of proteins that have been previously associated with microcephaly in human genetic disorders and/or animal models. This study builds on previously published interacting networks of ZIKV and genes related to autosomal recessive primary microcephaly to generate a catalog of human cellular targets of ZIKV proteins implicated in processes related to microcephaly in humans. Collectively, this data can be used as a resource for future characterization of ZIKV infection biology and help create a basis for the discovery of drugs which may disrupt the interaction and reduce the health damage to the fetus.

The investigation of membrane proteins, key constituents of cells, is hampered by the difficulty and complexity of their in vitro synthesis, of unpredictable yield. Cell-free synthesis is herein employed to unravel the impact of the expression construct on gene transcription and translation, without the complex regulatory mechanisms of cellular systems. Through the systematic design of plasmids in the immediacy of the start of the target gene, it was possible to identify translation initiation and the conformation of mRNA as the main factors governing the cell-free expression efficiency of the human voltage dependent anion channel (VDAC), a relevant membrane protein in drug-based therapy. A simple translation initiation model was developed to quantitatively assess the expression potential for the designed constructs. A scoring function is proposed that quantifies the feasibility of formation of the translation initiation complex through the ribosome-mRNA hybridization energy and the accessibility of the mRNA segment binding to the ribosome. The scoring function enables to optimize plasmid sequences and semi-quantitatively predict protein expression efficiencies. This scoring function is publicly available as webservice XenoExpressO at rna.tbi.univie.ac.at.

In the intricate dance between viruses and host cells, RNA-binding proteins (RBPs) serve as crucial orchestrators of gene expression and cellular processes. We will delve into the riveting realm of viral hijacking, where viruses deftly exploit host RBPs to manipulate cellular machinery for their replication and pathogenesis. Through a masterstroke of molecular subterfuge, viruses co-opt RBPs involved in various facets of RNA metabolism - from transcription to degradation - to promote viral gene expression and evade host immune defenses. This manipulation leads to global alterations in cellular RNA metabolism, impacting essential host genes vital for immune responses and homeostasis.Unveiling this clandestine alliance between viruses and RBPs is not just a scientific pursuit, but a critical imperative for devising innovative antiviral strategies to disrupt these interactions. By unraveling the intricate interplay between viral proteins and host RBPs throughout the viral life cycle - from entry to assembly - researchers aim to identify vulnerabilities that can be targeted for therapeutic intervention. Strategies such as disrupting viral protein-RBP interactions hold promise for inhibiting viral replication and curbing pathogenesis, offering a beacon of hope in the battle against viral infections.Our manuscript elucidates the indispensable roles played by RBPs in viral replication, translation, and pathogenesis, shedding light on the molecular mechanisms driving viral success. Delving deeper, it explores how viruses intricately entwine with host RBPs, manipulating cellular signaling pathways to create a hospitable environment for viral spread. By dissecting these manipulative tactics, researchers uncover new targets for antiviral therapy, envisioning a future where tailored interventions disrupt viral-host RBP interactions with precision and efficacy.As the narrative unfolds, the therapeutic implications of targeting RBPs or their interactions with viral proteins emerge as a promising frontier in the fight against viral infections. From small molecule inhibitors to RNA-based therapeutics, innovative approaches are on the horizon, offering new avenues for combatting viral diseases. We set the stage for future research, beckoning researchers to delve deeper into the molecular intricacies of viral hijacking of RBPs and charting a course towards novel therapeutic interventions that promise to reshape the landscape of antiviral therapy.\Ultimately, it beckons the scientific community to embark on a voyage of discovery, unraveling the secrets of viral hijacking of RBPs and paving the way for transformative advances in antiviral therapeutics. The stage is set for a new chapter in the battle against viral infections, where knowledge becomes the sword and innovation the shield against the pernicious machinations of viral pathogens.

Reinforcement corrosion due to chloride attack is of major economic significance for reinforced concrete structures. Pozzolans are known to inhibit corrosion initiation mainly by reducing concrete permeability. However, there is evidence in the literature that changes in the chemical environment in the concrete due to the pozzolans may be creating improved corrosion resistance, by themselves. In this study, the composition of a pore solution of mature hydrated cement paste containing silica-fume at different ratios was analyzed. The electrochemical behavior of reinforcing steel was studied in simulated pore solutions with silicate concentrations ranging from 0 to 35.6 mM, which are within the concentration range found by pore solution extraction to be up to 49 mM. Polished reinforcing steel specimens were used for cyclic voltammetry in simulated pore solutions with chloride concentrations of 10-20%. Better corrosion protection was found with increasing silicate concentration up to 3.56 mM. This was indicated by lower corrosion currents both in the passive state and after anodic activation. Anodic activation of steel in a 35.6 mM silicate solution with 20% NaCl yielded a higher potential than the anterior potential.

A new design scheme is proposed for twisting the walls of a microchannel, and its performance is demonstrated numerically. The numerical study was carried out for a T-shaped microchannel with twist angles in the range of 0 to 34π. The Reynolds number range was 0.15 to 6. The T-shaped microchannel consists of two inlet branches and an outlet branch. The mixing performance was analyzed in terms of the degree of mixing and relative mixing cost. All numerical results show that the twisting scheme is an effective way to enhance the mixing in a T-shaped microchannel. The mixing enhancement is realized by the swirling of two fluids in the cross section and is more prominent as the Reynolds number decreases. The twist angle was optimized to maximize the DOM, which increases with the length of the outlet branch. The twist angle was also optimized in terms of the relative mixing. The two optimum twisting angles are generally not coincident. The optimum twist angle shows a dependence on the length of the outlet branch but it is not affected much by the Reynolds number.

Pathogenicity of many bacteria including Bacillus cereus and Staphylococcus aureus depends on pore-forming toxins (PFTs), which cause lysis of host cells by forming pores in membranes of eukaryotic cells. Bioinformatic analysis revealed in over 600 PFTs a region homologous to the Lys171-Gly250 sequence in hemolysin II (HlyII) from B. cereus, which we designated as “homologous peptide”. Three β-barrel PFTs were used for a detailed comparative analysis. Two of them –HlyII and cytotoxin K2 (CytK2), – are synthesized in Bacillus cereus sensu lato; the third – S. aureus α-toxin (Hla) – is the most investigated representative of the family. Protein modeling showed certain amino acids of homologous peptide to be located on the surface of the monomeric forms of these β-barrel PFTs. We obtained monoclonal antibodies against both a cloned homologous peptide and a 14-membered synthetic peptide DSFNTFYGNQLFMK as part of homologous peptide. The HlyII, CytK2 and Hla regions recognized by the obtained antibodies, as well as an antibody capable of suppressing the hemolytic activity of CytK2, were identified in the course of the work. Antibodies capable of recognizing PFTs of various origins can be useful tools for both identification and suppression of the cytolytic activity of PFTs.

Wall Shear Stress (WSS) abnormalities in carotid artery blood flow are key hemodynamic factors leading to arterial endothelial damage, atherosclerotic plaque formation, and carotid artery stenosis. Precise simulation of carotid artery blood flow WSS in vitro play an important role in understanding the underlying hemodynamic mechanism of carotid artery stenosis. This study presents a design for a microfluidic cell culture chamber with a variable cross-section and a step structure, leveraging microfluidic technology and principles of fluid dynamics. We propose an optimization strategy for microchannel dimensions based on Computational Fluid Dynamics (CFD) simulations. This strategy aims to replicate the distinct WSS waveform features found at various locations within the carotid bifurcation as observed in vivo. Our simulations indicate that with a step height of 0.09 mm, a width of 4 mm for the initial segment, and 5 mm for the subsequent wider channel, the device can effectively model the characteristics of low oscillatory WSS seen at sites of carotid sinus stenosis. Furthermore, it accurately represents the high-magnitude pulsatile WSS waveforms in the more uniform arterial sections downstream of the carotid sinus. The study also reveals that vortex formation and variations in low oscillatory WSS within the stepped section of the microchannel correlate with the step's height and width, as well as with the dimensions of the wider channel section. An increase in step width leads to a decrease in both the vortex area and the magnitude of negative WSS oscillations. When the step height is less than 0.03 mm, vortex formation is inhibited, challenging the simulation of low oscillatory WSS patterns. The variable cross-section microfluidic channel developed in this study provides a platform for simulating carotid artery WSS waveforms and facilitates research into the interplay between low oscillatory WSS at sites of carotid sinus stenosis and arterial endothelial dysfunction.

Low-loss photonic waveguides in lithium niobate offer versatile functionality as nonlinear frequency converters, switches, and modulators for integrated optics. Combining the flexibility of laser processing with liquid phase epitaxy we have fabricated and characterized lithium niobate channel waveguides on lithium niobate and lithium tantalate. We used liquid phase epitaxy with K2O flux on laser-machined lithium niobate and lithium tantalate substrates. The laser-driven rapid-prototyping technique can be programmed to give machined features of various sizes, and liquid phase epitaxy produces high quality single-crystal, lithium niobate channels. The surface roughness of the lithium niobate channels on a lithium tantalate substrate was measured to be 90 nm. The lithium niobate channel waveguides exhibit propagation losses of 0.26 ± 0.04 dB/mm at a wavelength of 633 nm. Second harmonic generation at 980 nm was demonstrated using the channel waveguides, indicating that these waveguides retain their nonlinear optical properties.

PIEZO channels PIEZO1 and PIEZO2 are the newly identified mechanosensitive, non-selective cation channels permeable to Ca2+. In higher vertebrates, PIEZO1 expresses ubiquitously in most of the tissues and cells while PIEZO2 expresses more specifically in the peripheral sensory neurons. PIEZO channels contribute to a wide range of biological behaviors and developmental processes, therefore driving a significant attention in the effort to understand their molecular properties. One prominent property of PIEZO channels is their rapid inactivation, which manifests itself as a decrease of channel open probability in the presence of a sustained mechanical stimulus. Lack of the PIEZO channel inactivation is linked to various mechanopathologies emphasizing the significance of studying this PIEZO channel property and the factors affecting it. In the present review, we discuss the mechanisms underlying the PIEZO channel inactivation, its modulation by interaction of the channels with lipids and/or proteins, and how the changes of PIEZO inactivation by the channel mutations can cause a variety of diseases in animals and humans.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, wings, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects and all other arthropods. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. As a means of renaming this protein family, this review article discusses the latest findings (“CSP” is attached to the tail of bigger intracellular proteins) and attempts to compel all the data. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins) and use at least for abbreviations for distinctive animal proteins the common peptide 5-letter code, such as “Bommo-4CSPs”.

With the development of free trade port in Hainan Island, the construction of tourist roads around the island is also in full swing. Under the weather conditions of strong typhoon and rainstorm in Hainan, the highway cutting slope built on the coastal weak sandy terraces has strong sand loss and is easy to be scour by rainfall. MICP green spray irrigation solidification technology is used to strengthen the sandy cutting, and pore water pressure monitoring is carried out on the slope model during MICP solidification and rainfall scour. Combined with the model pore water pressure and flow slip failure pattern, dynamic analysis was carried out. The results show that MICP sprinkler irrigation technology can solidified the surface of the slope model in a short time, and the cementation depth of the model reaches 4cm after three sets of rotation reinforcement. The surface reinforcement effect is good, and the sand samples are closely connected. Under the erosion effect of simulated rainfall intensity, the sand loss of the slope is weakened, and no sand binding damage occurs, and the integrity is enhanced. Due to the cementation between sand grains, most of the rainfall was converted into runoff, and the slope slid after 150s. When the slope began to slip, the leading edge of the slope model lost sand and unloaded, and the failure mode was graded creep slip failure. Finally, the slope was divided into several blocks due to the continuous expansion of cracks after the slope failure. The erosion stability of the sandy slope under heavy rains is optimized and the sand loss is prevented effectively. In this study, a new method of MICP remediation techniques is proposed, which provides a new test basis for the application of MICP technology in practical engineering.

The influence of pore size on the toughness of Fe-Mo-Cu-C sintered and carburized components was investigated. The charpy impact value of the component made from Fe-0.4%Mo diffusion-alloyed steel powder mixed with 2%Cu powder and 0.3% graphite powder significantly increased with a decrease in pore size. The highest impact value of 17 J/cm2 was obtained at the average pore size of 12 µm. This value was 25% higher than that of the sintered and carburized component made from conventional Fe- 4%Ni-1.5%Cu-0.5%Mo alloyed steel powder called 4Ni even though the component was made from a Ni-free alloyed steel powder. The mechanism of the improvement of the impact value by pore size refinement and the influence of microstructural difference between the components made from Fe- 0.4%Mo diffusion-alloyed steel powder and 4Ni on toughness is discussed based on optical microstructural observation and crystal orientation analysis data.

We propose a deep-learning approach for the joint MIMO detection and channel decoding problem. Conventional MIMO receivers adopt a model-based approach for MIMO detection and channel decoding in linear or iterative manners. However, due to the complex MIMO signal model, the optimal solution to the joint MIMO detection and channel decoding problem (i.e., the maximum likelihood decoding of the transmitted codewords from the received MIMO signals) is computationally infeasible. As a practical measure, the current model-based MIMO receivers all use suboptimal MIMO decoding methods with affordable computational complexities. This work applies the latest advances in deep learning for the design of MIMO receivers. In particular, we leverage deep neural networks (DNN) with supervised training to solve the joint MIMO detection and channel decoding problem. We show that DNN can be trained to give much better decoding performance than conventional MIMO receivers do. Our simulations show that a DNN implementation consisting of seven hidden layers can outperform conventional model-based linear or iterative receivers. This performance improvement points to a new direction for future MIMO receiver design.

Orthohepadnavirus causes chronic hepatitis in a broad range of mammals, including primates, cats, woodchucks, and bats. Hepatitis B virus (HBV) X protein inhibits type-I interferon (IFN) signaling, promoting HBV escape from the innate immune system to establish persistent infection. However, whether X proteins of Orthohepadnavirus viruses in the other species have similar inhibitory activity remains unknown. Here, we investigated the anti-IFN activity of 17 Orthohepadnavirus X proteins derived from various hosts. We observed conserved activity of Orthohepadnavirus X proteins in inhibiting TIR-domain-containing adaptor protein inducing IFN-β (TRIF)-mediated IFN-β signaling pathway through TRIF degradation. X proteins from domestic cat hepadnavirus (DCH), a novel member of Orthohepadnavirus, inhibited mitochondrial antiviral signaling protein (MAVS)-mediated IFNβ signaling pathway comparable with HBV X. These results indicate that inhibition of IFN signaling is conserved in Orthohepadnavirus X proteins.

The combination of neural network and beamforming has been proved to be very effective in multi-channel speech separation. But its performance faces a challenge in complex environment. In this paper, an iteratively refined multi-channel speech separation method is proposed for the challenge, where the proposed is composed of initial separation and iterative separation. In initial separation, the time-frequency domain dual-path recurrent neural network neural network (TFDPRNN), minimum variance distortionless response (MVDR) beamformer and post-separation (also TFDPRNN) are cascaded for obtaining the first additional input in iterative separation. In iterative separation, the MVDR beamformer and post-separation are iteratively used, where the output of the MVDR beamformer is used as an additional input of the post-separation network and the final output comes from post-separation module. This iteration of the beamformer and post-separation is fully employed for promoting their individual optimization, which ultimately improves the overall performance of speech separation in multi-speaker scenarios. Experiments on the spatialized version of the WSJ0-2mix corpus show that our proposed method is significantly better than the current popular methods. In addition, the method also has a good effect on the dereverberation task.

Network Simulators (NS) is typically used to study services and applications in complex scenarios due to the infeasibility of deploying real testbeds. This is the case of Mobile Ad hoc Networks (MANETs) which can be extensively used in emergency situations or to gather information without infraestructure. An important factor to get realiable results in the MANETs’ simulations is the wireless channel module of NSs. In this report, we explain how thw wireless channel is implemented in NS-3 and it can be configured.

Synucleins are a family of small, soluble proteins mainly expressed in neural tissue and in certain tumors. Since their discovery, tens of thousands of scientific reports have been published about this family of proteins as they are associated to severe human diseases. Although the physiological function of these proteins still elusive, their relation with neurodegeneration and cancer was clearly described over the years. In this review, we summarize data connecting synucleins and cancer, going from the structural description of these molecules, to their involvement in tumor-related processes, and discuss the putative use of this proteins as cancer molecular biomarkers.

The Coronavirus Disease 2019 (COVID-19) is a new viral infection caused by the severe acute respiratory coronavirus 2 (SARS-CoV-2). Genomic analyses have revealed that SARS-CoV-2 is related to Pangolin and Bat coronaviruses. In this report, a structural comparison between the Sars-CoV-2 Envelope and Membrane proteins from different human isolates with homologous proteins from closely related viruses is described. The analyses here reported show the high structural similarity of Envelope and Membrane proteins to the counterparts from Pangolin and Bat coronavirus isolates. However, the comparisons have also highlighted structural differences specific of Sars-CoV-2 proteins which may be correlated to the cross-species transmission and/or to the properties of the virus. Structural modelling has been applied to map the variant sites onto the predicted three-dimensional structure of the Envelope and Membrane proteins.

The aim of this study was characterization of some dairy drinks based on Milk Serum regarding major whey proteins (WP) and free amino acids (FAAs) using reversed phase high performance liquid chromatographic (RP-HPLC) methods. The studied WP, -lactalbumin (-La), bovine serum albumin (BSA), -lactoglobulin A (-Lg A) and -lactoglobulin B (-Lg B) were separated on Aeris XB-C18 column at 214 nm detection. The RP-HPLC method was validated by selectivity, linearity (R2 ≥0.99), sensitivity (LOQ, 1.35–10.08 µg mL−1), accuracy (recovery 96.79-103.07%) and precision (% RSD ≤ 4.13%). The total studied WP in studied dairy drinks varied between 1.42 and 3.047 g·L-1. The chromatographic profile of FAAs (aspartic acid, glutamic acid, serine, histidine, arginine, glycine, threonine, alanine, tyrosine, cysteine, tryptophan, methionine, valine, phenylalanine, isoleucine, leucine and lysine) was determined in lyophilized concentrate of Milk Serum by RP-HPLC using pre-column derivatization reaction with orthophthalaldehyde (OPA). The total studied FAAs in studied samples varied between 1.103 and 1.119 mg·g-1. Moreover, the Milk Serum showed bacteriostatic activity against two bacterial strains Escherichia coli and Staphylococcus aureus. The obtained results confirm that dairy drinks based on the Milk Serum constitutes a valuable sources of bioactive components with benefits for human healthy nutrition.

To prevent CO2 leakage and ensure the safety of long-term CO2 storage, it is essential to investigate the flow mechanism of CO2 in complex pore structures at the pore scale. This study focuses on reviewing the experimental, theoretical, and numerical simulation studies on the microscopic flow of CO2 in complex pore structures during the last decade. For example, advanced imaging techniques, such as X-ray computed tomography (CT) and nuclear magnetic resonance (NMR), are used to reconstruct the complex pore structures of rocks. Mathematical methods, such as Darcy's law, Young–Laplace’s law, and the Navier-Stokes equation, are used to describe the microscopic flow of CO2. Numerical methods, such as the lattice Boltzmann method (LBM) and pore network (PN) model, are used for numerical simulation. The application of these experimental and theoretical models and numerical simulation studies is discussed, considering the effect of complex pore structures. Finally, future research is suggested to focus on: (1) Conducting real-time CT scanning experiments of CO2 displacement combined with the developed real-time CT scanning clamping device to realize real-time visualization and provide quantitative description of the flow behavior of CO2 in complex pore structures; (2) The effect of pore structures change on the CO2 flow mechanism caused by the chemical reaction between CO2 and the pore surface, the flow theory of CO2 considering wettability and damage theory in a complex pore structures; (3) The flow mechanism of multi-phase CO2 in complex pore structures; (4) The flow mechanism of CO2 in the pore structures at multiscale and the scale upgrade from microscopic to mesoscopic to macroscopic. Generally, this study focuses on reviewing the research progress of CO2 flow mechanisms in complex pore structures at the pore scale and affords an overview of potential advanced developments to enhance the current understanding of CO2 microscopic flow mechanisms.

It is important to distinguish between natural earthquakes and those induced by CO2 injection at carbon capture and storage sites. For example, the 2004 Mw 6.8 Chuetsu earthquake occurred close to the Nagaoka CO2 storage site during gas injection, but we could not quantify whether the earthquake was due to CO2 injection or not. Here we simulated changes of pore pressure during CO2 injection at the Nagaoka site and compared them with estimated natural seasonal fluctuations of pore pressure due to rainfall and snowmelt as well as estimated pore pressure increases related to remote earthquakes. We clearly distinguished changes of pore pressure due to CO2 injection from those due to rainfall and snowmelt. The simulated local increase in pore pressure at seismogenic fault area was much less than the seasonal fluctuations related to precipitation and increases caused by remote earthquakes, and the lateral extent of pore pressure increase was insufficient to influence seismogenic faults. We also demonstrated that pore pressure changes due to distant earthquakes are capable of triggering slip on seismogenic faults. The approach we developed could be used to distinguish natural from injection-induced earthquakes and will be useful for that purpose at other CO2 sequestration sites.

The study investigates the evolution of soil pore structure and shear strength deterioration in compacted clayey soil under controlled wetting and drying (wd) cycles, which are expected to become more frequent due to climate change. Thirty soil samples were compacted at optimal moisture content and 90% of maximum dry density. These samples were then subjected to 0, 1, 5, 10, and 15 controlled wd cycles from saturation to the wilting point, and volumetric changes were recorded during each cycle. After the wd treatment, the soil samples were scanned using X-ray Computed Tomography (CT) at 50 μm resolution and then sheared under unconsolidated-undrained and consolidated-undrained conditions in a triaxial test. Significant shrinkage and swelling of soil samples were observed during wd cycles, with average volumetric strain fluctuating between +12% at saturation and -5% at the wilting point. X-ray CT visualisation and analysis revealed higher porosity, more prominent pores and increased pore length in soil samples with increasing wd cycles. Both undrained and effective soil shear strength markedly decreased with increasing wd cycles. CT-derived macroporosity and pore length were significant predictors of the soil's undrained and effective shear strength when exposed to wd cycles. The findings emphasise the considerable impact of climate change, specifically wd cycles, on clayey soil, highlighting the need for consideration in the design of earth-based infrastructure.

The structure of turbulent flow over non-flat surfaces is a topic of major interest in practical applications in both engineering and geophysical settings. A lot of work has been done in the fully rough regime at high Reynolds numbers where the effect on the outer layer turbulence structure and the resulting friction drag is well documented. It turns out that surface topology plays a significant role on the flow drag especially in the transitional roughness regime and therefore, hard to characterize. Survey of literature shows that roughness function depends on the interaction of roughness height, flow Reynolds number and topology shape. In addition, if the surface topology contains large enough scales then it can impact the outer layer dynamics and in turn modulate the total frictional force. Therefore, it is important to understand the mechanisms underlying drag increase from systematically varied surface undulations in order to better interpret quantifications based on mean statistics such as roughness function. In this study, we explore the mechanisms that modulate the turbulence structure over a two-dimensional (2D) sinusoidal wavy surface with a fixed amplitude, but varying slope. To accomplish this, we model the turbulent flow between two infinitely wide 2D wavy plates at a friction Reynolds number, $Re_{\tau}=180$. We pursue two different but related flavors of analysis. The first one adopts a roughness characterization flavor of such wavy surfaces. The second one focuses on understanding the non-equilibrium near surface turbulence structure and their impact on roughness characterization. Analysis of the different statistical quantifications show strong dependence on wave slope for the roughness function indicating drag increase due to enhanced turbulent stresses resulting from increased production of vertical velocity variance from the surface undulations.

The Inverted F Antenna (IFA) with the parasitic element on a finite conducting plane is proposed in the range frequency of 0.1 to 5.5 GHz and its characteristics are analyzed numerically. In this research, the parasitic element and the main IFA are investigated to obtain the resonance frequency for multiband operation purposes. The parasitic element is placed beneath adjusted to the main IFA to derive more frequency bands. The distance between the parasitic element and main horizontal element extremely affects the performance of the IFA. It is found that when the parasitic element is located closer to the conducting plane, this element is coupled by the current on the conducting plane. Consequently, the return loss bandwidth becomes narrower. Therefore, the gain of the proposed IFA becomes a bit higher. The antenna gain is about 8.21 dB at band #3 (λ_1.747), 7.43 dB at band #5 (λ_2.967) and 8.82 dB at band #6 (λ_4.023). This occurs when the calculation condition is antenna height h1 = 23 mm, h2 = 21 mm, horizontal antenna elements L = 173.2 mm, L1 = 140.9 mm and Lp = 152 mm, shorted element Ls = 30.7 mm, the distance between parasitic element and shorted element pyl = 5 mm. While the size of conducting plane is considered pxp+pxm by pyp+pym as 57.5+57.5 mm by 200+50 mm. In the numerical analysis, the electromagnetic simulator WIPL-D based on Method of Moment is used. The results show that the proposed IFA has UHF and SHF channel receiver which are suitable for advanced wireless service (band #3), mobile phones, Bluetooth, maritime service, radiolocation service (band #5) and radars, mobile phones, commercial wireless LAN (band #6).

Ion channels serve many cellular functions including ion homeostasis, volume regulation, signaling, nutrient acquisition, and developmental progression. Although the complex lifecycles of malaria parasites necessitate ion and solute flux across membranes, whole genome sequencing of the human pathogen, Plasmodium falciparum, revealed remarkably few orthologs of known ion channel genes. Contrasting with this, biochemical studies have implicated channel-mediated flux of ions and nutritive solutes across several membranes in infected erythrocytes. Here, I review advances in the cellular and molecular biology of ion channels in malaria parasites. These studies have implicated novel parasite genes in the formation of at least two ion channels, with additional ion channels likely present at various membranes and parasite stages. Computational approaches that rely on homology to known channel genes from higher organisms will not be very helpful in identifying the molecular determinants of these activities. Given their unusual properties, novel molecular and structural features, and essential roles in pathogen survival and development, parasite channels should be promising targets for therapy development.

In this paper, we develop a tractable mathematical model and emulation framework for communicating information through water using acoustic signals. Water is considered as one of the most complex mediums to model owing to its vastness and variety in characteristics depending on the scenario, what kind of water-body (lakes, rivers, tanks, sea etc.) and geographical location of the water-body is considered. Our proposed mathematical model involves the concept of damped harmonic oscillators to represent the medium (water) and Milne’s oscillator technique to map the interaction between the acoustic signal and water. Wave equations formulated for acoustic pressure and acoustic wave velocity are used to characterize the travelling acoustic signal. Signal strength, phase shift and time-delay generated from the mathematical model are fed to a Simulink-based emulator framework to generate channel samples and channel impulse responses. The emulator uses wide sense stationary uncorrelated scattering (WSSUS) assumption and finite sum-of-sinusoids (SOS) with uniformly distributed phase to generate the channel samples. Using the emulator platform it is possible to generate amplitude variation profile, Doppler shift and spread experienced by any travelling signal through different underwater communication scenarios. Such an emulator platform can be used to simulate different communication scenarios, underwater network topologies, data to train different learning models and predict performance of different modulation, multiplexing, error correction and multi-access techniques for underwater acoustic communications (UWAC) systems.

in this paper, the optical channel performance with respect to varying scintillation index parameters is studied. Where different channel effects are studied and analyzed. In free-space optical (FSO) communication, the major drawback of the optical communication system is the atmospheric turbulence (AT). This effect is nonlinear with optical channel altitude being changed. Therefore, the power margenal (PM) required for such a channel is also inconstant respectively. In this thesis, we analyze AT effect on the optical channel with different altitudes. Such that we found the difference in the range of PM required for such optical link distance. In our result, the Bit Error Rate (BER) VS. PM required is measured. The optical channel model is Log-Normal considered and the BER threshold BER^th = 10^-10 is taken.

In line with Pomeau’s conjecture about the relevance of directed percolation (DP) to turbulence onset/decay in wall-bounded flows, we propose a minimal stochastic model dedicated to the interpretation of the spatially intermittent regimes observed in channel flow before its return to laminar flow. Numerical simulations show that a regime with bands obliquely drifting in two stream-wise symmetrical directions bifurcates into an asymmetrical regime, before ultimately decaying to laminar flow. The model is expressed in terms of a probabilistic cellular automaton evolving von Neumann neighbourhoods with probabilities educed from a close examination of simulation results. It implements band propagation and the two main local processes: longitudinal splitting involving bands with the same orientation, and transversal splitting giving birth to a daughter band with orientation opposite to that of its mother. The ultimate decay stage observed to display one-dimensional DP properties in a two-dimensional geometry is interpreted as resulting from the irrelevance of lateral spreading in the single-orientation regime. The model also reproduces the bifurcation restoring the symmetry upon variation of the probability attached to transversal splitting, which opens the way to a study of the critical properties of that bifurcation, in analogy with thermodynamic phase transitions.

Ion channels contribute fundamental properties to all cell membranes. The ion channels are highly diverse in conductivity, structure, location and function. However, many of them can be regulated by common mechanisms, such as voltage or (de-)phosphorylation. Considering primarily pain-related ion channels, this review covers more novel and less known features of ion channel function, also with the aim to transfer knowledge between fields, which get inevitably more separate due to their size.

Security is a major topic in recent researchers, and finding new methods deliver was the motivations for this research to emphasize and as an awareness to browsers developers to handle images with more care and to enhance exploit detection technology in the browser, as this paper proves that hackers now can attack users with just an image.

Integrated crop-livestock production (ILP) is an interesting alternative for more sustainable soil use. However, more studies are needed to analyze soil pore properties under ILP at the micrometer scale. Thus, this study proposes a detailed analysis of soil pore architecture at the micrometer scale in three dimensions. For this purpose, samples of an Oxisol under ILP subjected to minimum tillage (MT) and no-tillage (NT) with ryegrass as cover crop (C) and silage (S) were investigated. The soil micromorphological properties of the soil were analyzed using X-ray microtomography. The MT(C) system showed the highest values of porosity (c. 20.4%), connectivity (c. 32.8×103), volume (c. 26%), and number of pores (c. 32%) in a rod-like shape. On the other hand, the MT(S), NT(C), and NT(S) systems showed higher tortuosities (c. 2.2, c. 2.0, and c. 2.1) and lower pore connectivities (c. 8.3×103, c. 6.9×103, and c. 6.2×103), especially in S use. Ellipsoidal and rod-shaped pores predominated over spheroidal and disc-shaped pores in all treatments. The results of this study show that the use of ryegrass as a cover crop improves soil physical properties, especially in MT. For S use, the type of soil management (MT or NT) did not show any differences.

The study focuses on a novel porous TiNi-based material for ophthalmic orbital implants which was produced by self-propagating high-temperature synthesis (SHS) and, after proper surface modification, possesses a specific microstructure of its surface pores, which makes it attractive for biomedical use in implants. After preparation via SHS, the obtained porous TiNi material was etched in acidic environment, to get rid of its surface Ti2Ni secondary-phase particles. This was found to improve the material’s surface morphology, adding micro-roughness to its macro-rough pores. As a result, cell growth tests conducted on the material demonstrated improved cell adhesion and growth kinetics on such a porous material with improved roughness. Finally, the material was tested in vivo as an ophthalmic orbital implant, demonstrating good biocompatibility, good degree of biointegration with surrounding eyeball tissues, and no signs of rejection after as long as 180 days. Thus, the novel porous TiNi-based material shows promise for its use in ophthalmic implantology, for instanse for manufacturing musculoskeletal stumps of the eyeball after evisceration, as it is biocompatible, has a high tissue-implant integration potential and demonstrates reduced risks of exposure and rejection of the implant.

Tight gas, a category of Deep Green Energy Resources, rely on advanced intelligent monitoring methods for their extraction. Conventional logging for reservoir evaluation relies on logging data and the manual setting of evaluation criteria to classify reservoirs. However, the complexity and heterogeneity of tight reservoirs pose challenges in accurately identifying target layers by using traditional well-logging techniques. Machine learning may hold the key to solving this problem, as it enables computers to learn without being explicitly programmed and manually added rules. Therefore, it is possible to make reservoir evaluation via using machine learning methods. In this paper, the reservoir quality index (RQI) and porous geometric parameters obtained from the optimized inversion of the spherical-tubular model are adopted to evaluate the reservoir. Then, three different machine learning approaches, the random forest (RF) algorithm, support vector machine (SVM) algorithm, and extreme gradient boosting (XGB) algorithm, are utilized for reservoir classification. The selected dataset covers more than 7,000 samples from five wells. The data from four wells are arranged as the training dataset, and the data of the remaining one well is designed as the testing dataset to calculate the prediction accuracies of different machine learning algorithms. Among them, accuracies of RF, SVM, and XGB are all higher than 90%, and XGB owns the highest result by reaching 97%. Machine learning based approaches can greatly assist reservoir prediction by implementing the well-logging data. The research highlights the application of reservoir classification with a higher prediction accuracy by combining machine learning algorithms with NMR logging based pore structure characterization, which can provide a guideline for sweet spot identification within the tight formation. This not only optimizes resource extraction but also aligns with the global shift towards clean and renewable energy sources, promoting sustainability and reducing the carbon footprint associated with conventional energy production. In summary, the fusion of machine learning and NMR logging based reservoir evaluation plays a crucial role in advancing both energy efficiency and the transition to cleaner energy sources.

Pore structure characterization and fractal analysis have great significance for understanding and evaluating tight limestone reservoirs. In this work, the pore structure of tight limestone is characterized combined with low-temperature nitrogen adsorption (LTNA) and low-field nuclear magnetic resonance (NMR), and the fractal dimension of tight limestone pore structure is discussed based on LTNA and NMR data. The results indicate that the pores of tight limestone have H3 and H4 types, the pore size distribution (PSD) of H3 type is a wave distribution ranging from 2 to 10 nm, and the PSD of H4 type is a unimodal distribution ranging from 2 to 10 nm. The transverse relaxation time (T2) spectrum of tight limestone shows single peak (DF), double peak (SF) and three peak (TF), and the T2 spectrums for micropores, mesopores and macropores range from 0.1 to 10 ms, from 10 to 100 ms, and greater than 100 ms, respectively. The LTNA fractal dimension of tight limestone (DL) ranges between 2.4446 and 2.7688, with an average of 2.5729, and the NMR fractal dimensions of micropores (DNMR1), mesopores (DNMR2) and macropores (DNMR3) are distributed between 0.3744 to 1.1293, 2.4263 to 2.9395 and 2.6582 to 2.9989, respectively. Moreover, there is no correlation between fractal dimension and permeability and porosity, a negative correlation between DL and average pore radius, a positive correlation between DL and specific surface area, and a positive correlation between DNMR2 and DNMR3 and micropore content, while DNMR2 and DNMR3 are negatively correlated with the content of mesopores and macropores.

Phα1β a spider peptide, purified from the venom of Phoneutria nigriventer inhibits high voltage calcium channels and is antagonist of TRPA1 receptor two important pain transduction path-ways. In the last 15 years, we have showed, in preclinical tests with Phα1β native and recombi-nant in rodent models of pain the potential of Phα1β to become a new analgesic drug. Evaluation of new drug on human ERG channel is requirement of the regulatory agencies. For the hERG channel inhibition assay it was used the commercial kit FLIPR® Potassium Assay. It was tested the effect of Phα1β and as positive control dofetilide, a well characterized hERG block-er. Phα1β 56, 225, 450 and 900 pMol caused at a higher concentration a very weak inhibition of the hERG channel activity of about 13.47 % with channel inhibition at 50%, IC50 > 900 pMol. Dofetilide (0.0001 - 10 µM), a known hERG inhibitor, caused a well-known, concentra-tion-dependent inhibition of the hERG channel with a mean IC50 of 0.1642 µM (0.1189 – 0.2282 µM. For the cytotoxicity assay, Phα1β concentrations of 56, 225, 450 and 900 pMol incubated for 24 h with HEK293-hERG cells did not alter the viability of the HEK293-hERG cells. It is con-cluded that Phα1β even at high concentrations does not interfere with hERG channels.

A recent paper demonstrates the importance of the linker region joining the two SNARE motifs of the neuronal t-SNARE SNAP25 for maintaining rates of secretion with roles for distinct segments in speeding fusion pore expansion (Shaaban et al., 2019, Elife. 8). Remarkably, lipid perturbing agents rescue a palmitoylation-deficient phenotype that includes slow fusion pore expansion, suggesting that protein-protein interactions have a role not only in bringing together the granule or vesicle membrane with the plasma membrane but also in orchestrating protein-lipid interactions leading to the fusion reaction. Furthermore, biochemical investigations demonstrate the importance of the C-terminal domain of the linker in the formation of the plasma membrane t-SNARE acceptor complex for synaptobrevin2 (Jiang, et al., 2019, FASEB J. 33:7985-7994;Shaaban et al., 2019, Elife. 8). This insight, together with biophysical and optical studies from other laboratories (Wang, et al., 2008, Molecular Biology of the Cell. 19:3944-3955; Zhao, et al., 2013, Proc Natl Acad Sci U S A. 110:14249-14254) suggests that the plasma membrane SNARE acceptor complex between SNAP25 and syntaxin and the resulting trans SNARE complex with the v-SNARE synaptobrevin form just milliseconds before fusion.

Comparison between hydraulic and hydrologic computational methods is conducted in this study, regarding prismatic open channels under unsteady subcritical flow conditions. One-dimensional unsteady flow continuity and momentum equations are solved using explicit and implicit finite difference schemes for a symmetrical trapezoidal cross section, where the flow discharge and depth are the dependent variables. The results have been compared to those derived from Muskingum-Cunge hydraulic/hydrologic method as well as the commercial software HEC-RAS. The results from explicit and implicit code compare well to those from commercial software and hydraulic/hydrologic methods for long prismatic channels, thus directing the hydraulic engineer to quick preliminary design of prismatic open channels for unsteady flow with satisfactory accuracy.

For voltage-gated Ca2+ channel (VGCC), its α2δ subunits are traditionally considered to be auxiliary subunits that regulates VGCC trafficking to the plasma membrane. The antiepileptic, antinociceptive and anxiolytic gabapentin (GBP) has previously been shown to bind the VGCC α2δ subunits with high affinity to disrupt VGCC trafficking. Yet, the interaction between GBP and α2δ still remains poorly understood from a structural point of view. For instance, it is not clear yet what the structural implication is of α2δ-1-bound GBP against VGCC trafficking. With a set of experimental data-driven structural analysis of the VGCC α2δ-1 and its ligand GBP, this article postulates for the first time that: 1), α2δ-1 bound GBP stabilizes the α2δ-1-GBP complex structure; 2), α2δ-1 bound GBP restrains the conformational flexibility of α2δ-1; 3), α2δ-1-bound GBP establishes an electrostatic axis consisting of Q535 (Gln535)-R241 (Arg241)-GBP (gabapentin)-D452 (Asp452), which constitutes an energetically favourable contribution towards the structural stability of the α2δ-1-GBP complex and helps restrains the conformational flexibility and local structural rigidification of α2δ-1; and 4), GBP-induced local conformational inflexibility and structural rigidification of α2δ-1 is one key step in the pharmacological disruption of VGCC trafficking by GBP.

Various studies indicate that vaccination, especially with pneumococcal vaccines, protects against symptomatic cases of SARS-CoV-2 infection and death. This paper explores the possibility that pneumococcal vaccines in particular, but perhaps other vaccines as well, contain antigens that might be cross-reactive with SARS-CoV-2 antigens. Comparison of the glycosylation structures of SARS-CoV-2 with the polysaccharide structures of pneumococcal vaccines yielded no obvious similarities. However, while pneumococcal vaccines are primarily composed of capsular polysaccharides, some are conjugated to CRM197, a modified diphtheria toxin, and all contain about three percent protein contaminants, including the pneumococcal surface proteins PsaA, PspA and probably PspC. All of these proteins have very high degrees of similarity, using very stringent criteria, with several SARS-CoV-2 proteins including the spike protein, membrane protein and replicase 1a. CRM197 is also present in Hib and meningitis vaccines. Equivalent similarities were found at lower rates, or were completely absent, among the proteins in diphtheria, tetanus, pertussis, measles, mumps, rubella, and poliovirus vaccines. Notably, PspA and PspC are highly antigenic and new pneumococcal vaccines based on them are currently in human clinical trials so that their effectiveness against SARS-CoV-2 disease is easily testable.

Dual localization or dual targeting refers to the phenomenon by which identical, or almost identical, proteins are localized to two (or more) separate compartments of the cell. From previous work in the field, we had estimated that a third of the mitochondrial proteome is dual targeted to extra-mitochondrial locations and suggested that this abundant dual targeting presents an evolutionary advantage. Here we set out to study how many additional proteins whose main activity is outside mitochondria are also localized, albeit at low levels, to mitochondria (eclipsed). To do this we employed two complementary approaches utilizing the α-complementation assay in yeast to uncover the extent of such eclipsed distribution: one systematic and unbiased and the other based on Mitochondrial Targeting Signal (MTS) predictions. Using these approaches, we suggest 280 new eclipsed distributed protein candidates. Interestingly, these proteins are enriched for distinctive properties compared to their exclusively mitochondrial-targeted counterparts. We focus on one unexpected eclipsed protein-family of the Triose-phosphate DeHydrogenases (TDH), and prove that indeed their eclipsed distribution in mitochondria is important for mitochondrial activity. Our work provides a paradigm of deliberate eclipsed mitochondrial localization, targeting and function, and should expand our understanding of mitochondrial function in health and disease.

Formaldehyde (HCHO), an indoor volatile organic compound, is seriously harmful to human health. Therefore, green and effective decomposition of HCHO is essential. TiO₂ has been employed for the degradation of HCHO via photocatalytic generation of reactive oxygen species (ROS) (O^2-, ·OH), yet the low specific surface area of crystalline TiO₂ depressed the catalytic performance. Herein, we prepared TiO₂ aerogels with high specific surface area and high porosity by sol-gel method, and added PVA to introduce flexible molecular chains for pore size regulation. The photocatalytic performance test verifies that the pore size of TiO₂ aerogel is one of the important factors for HCHO decomposition. Notably, through the establishment of theoretical model and calculation, we validated that the efficiency of HCHO decomposition is related to the oxygen pressure in the pores of TiO₂ aerogel, and the oxygen pressure is inversely proportional to the pore size. Accordingly, the optimal pore size of TiO₂ aerogel for the photocatalytic HCHO decomposition is 2 nm~10 nm. This study provides a theoretical idea for TiO₂ aerogels in the decomposition reaction of HCHO, which is expected to inspire more breakthroughs in the study of TiO₂ aerogels for green chemistry.

Formaldehyde (HCHO), an indoor volatile organic compound, is seriously harmful to human health. Therefore, green and effective decomposition of HCHO is essential. TiO2 has been employed for the degradation of HCHO via photocatalytic generation of reactive oxygen species (ROS) (O2-, ·OH), yet the low specific surface area of crystalline TiO2 depressed the catalytic performance. Herein, we prepared TiO2 aerogels with high specific surface area and high porosity by sol-gel method, and added PVA to introduce flexible molecular chains for pore size regulation. The photocatalytic performance test verifies that the pore size of TiO2 aerogel is one of the important factors for HCHO decomposition. Notably, through the establishment of theoretical model and calculation, we validated that the efficiency of HCHO decomposition is related to the oxygen pressure in the pores of TiO2 aerogel, and the oxygen pressure is inversely proportional to the pore size. Accordingly, the optimal pore size of TiO2 aerogel for the photocatalytic HCHO decomposition is 2 nm-10 nm. This study provides a theoretical idea for TiO2 aerogels in the decomposition reaction of HCHO, which is expected to inspire more breakthroughs in the study of TiO2 aerogels for green chemistry.

Electrospun fiber scaffolds are widely used in small diameter vascular tissue engineering because they mimick organizational structure and biological function of natural extracellular matrix. However, there is still one problem of low patency rate in the long term. The main reasons are the mismatch of compliance and the easy formation of thrombus. Therefore, it is very important to promote the rapid endothelialization of small diameter tissue engineering blood vessels by regulating the topological structure and biological properties of electrospun fiber scaffolds. Firstly, crimped polylactic acid (PLA) fibers were prepared by heat treatment to mimick the crimped structure and nonlinear mechanical properties of the elastic membrane of blood vessel wall. It improved effectively the aspect ratio of human umbilical vein endothelial cells (HUVECs) and promoted lateral alignment and growth. Then, crimped PLA fibers with three levels of pore structure were prepared by thermal induced phase separation, vapor induced phase separation and laser ablation to enhance the degree of HUVECs infiltrarion and realize patterned cell growth. Crimped PLA fibers with three levels of pore structure promote rapid endothelialization of blood vessels, which is of great significance to achieve long term patency rate of small diameter tissue engineering blood vessels.

YouTube Kids serves as a dynamic and user-friendly resource for young learners to learn English. Its extensive library of instructional materials, which includes captivating animations and interactive movies, provides a rich and varied learning environment. Through the integration of play and exploration into language study, YouTube Kids creates a comfortable and engaging atmosphere that allows kids to improve their English language skills at their own pace. In this research article, a narrative literature review was employed as a qualitative methodology. Based on the gathered relevant literature, YouTube Kids presented such positive and negative impacts as a channel for English language acquisition. YouTube Kids is indeed a beneficial tool for young learners who are trying to learn English, but at the same time, it does have some potential disadvantages, as some videos may not employ the same standard or correctness of English, which could expose kids to improper grammar or pronunciation. Parents and teachers need to carefully select and keep an eye on the content their kids watch to ensure that their children's YouTube Kids content supports their language learning objectives. Through careful supervision and curation, parents and educators may maximize the usefulness of the site as a medium for teaching young learners English language skills while also minimizing any potential downsides.

Starting from the model of a slow-rolling missile with six degrees of freedom (6 DOF) in the body frame, a 6 DOF model in the Resal frame is obtained, which is used to linearize the coupled commanded motion. Based on the linearized model, we obtain the structural scheme of the commanded object and define the quality parameters. The obtained parameters have a complex representation (with real and imaginary parts) due to the coupling between longitudinal channels. Then, the kinematic guidance equations, the seeker equations and the actuator specific to the slow-rolling single-channel missile are defined using a switching function. The guidance kinematic equations, the seeker equations and the actuator model are linearized in the Resal frame, and the structural diagram of the homing missile is constructed. Starting from this, the characteristic polynomial having complex coefficients is determined and then analyzed with the Frank-Wall stability criterion. Based on the analysis, a stability range is determined for the navigation constant and a minimum and possibly a maximum limit for the time to hit the target is obtained. The stability range defined for the navigation constant on the linear model is finally validated on the nonlinear model in the body frame.

In the last decade, three-dimensional (3D) printing has allowed the field of complex microfluidic channels to expand rapidly towards channels with variable cross-sections (i.e., beyond simple rounded media with a constant diameter) and channels. Whose trajectory can be outside a single plane and has gained numerous macro- and nanoscale manufacturing advances. Three-dimensional printing is being explored for various biomedical applications and the fabrication of nanomedicines using additive manufacturing techniques. Employing 3D-printed templates for macro-to-micro interfacing, a passively operated microfluidic device was designed. The research seeks to fabricate a biodevice that enables insulin microdosing, creating a subsystem like a microvalve and a microchannel matrix using additive manufacturing techniques. Our systems feature designs that enhance fluid dynamics without affecting the stability of the insulin. We propose using Humalog insulin in tropical climates (up to 30°C) without refrigeration for 28 days. The microvalve has a spiral trajectory with four outlet channels distributed along it. These channels align with the microchannels organized in a 10 mm x 15 mm matrix with 25 microchannels, each with a 770 µm internal diameter. The system delivers a dose of 2,3 mL in 6 minutes. We designed these systems for insulin micro-dosing, but they can also serve similar devices for other drugs.

Zn2+ has been implicated in the regulation of intestinal redox and microbial homeostasis, and we recently reported that transient receptor potential canonical (TRPC) 6 channel activity contributes to intracellular Zn2+ homeostasis in mammalian cells. This study aims to investigate the role of TRPC6-mediated Zn2+ influx in stress resistance of intestine. Expression profile of TRPC1-C7 mRNAs in the actively inflamed mucosa from inflammatory bowel disease (IBD) patients was analyzed using GEO database. Systemic TRPC3-knockout (KO) and TRPC6-KO mice were treated with dextran sulphate sodium (DSS) to induce colitis. The Zn2+ concentration and the mRNA expression levels of oxidative/inflammatory markers in colon tissues were quantitatively analyzed, and gut microbiota profiles were compared. TRPC6 mRNA expression level was increased in IBD patients and DSS-treated mouse colon tissues. DSS-treated TRPC6-KO mice, but not TRPC3-KO mice, showed severe weight loss and increased disease activity index compared with DSS-treated WT mice. The mRNA abundances of antioxidant proteins were basically increased in TRPC6-KO colon, with changes in gut microbiota profiles. Treatment with TRPC6 activator prevented the DSS-induced colitis progression accompanied by increasing Zn2+ concentration. We suggest that TRPC6-mediated Zn2+ influx activity plays a key role in stress resistance against IBD, providing a new strategy for treating colitis.

Transient Receptor Potential Vanilloid 4 (TRPV4) channel is a non-selective cation channel, mostly permeable to calcium (Ca2+), which participates to intracellular Ca2+ handling in cardiac cells. It is widely expressed through the body and is activated by a large spectrum of physico-chemical stimuli, conferring it a role in a variety of sensorial and physiological functions. With-in the cardiovascular system, TRPV4 expression was reported in cardiomyocytes, endothelial cells (ECs) and smooth muscle cells (SMCs) where it modulates mitochondrial activity, Ca2+ ho-meostasis, cardiomyocytes electrical activity and contractility, cardiac embryonic development, fibroblast proliferation but also vascular permeability, dilatation and constriction. On the other hand, TRPV4 channels participate in several cardiac pathological processes such as development of cardiac fibrosis, hypertrophy, ischemia-reperfusion injuries, heart failure, myocardial infarc-tion, and arrhythmia. In this manuscript, we provide an overview of TRPV4 channel implica-tions in cardiac physiology and discuss the potential of TRPV4 channel as therapeutic target against cardiovascular diseases.

Next generation in-to-out-of body biomedical applications have adopted optical wireless communications (OWCs). However, by delving into the published literature, a gap is recognised in modeling the in-to-out-of channel, since most published contributions neglect the particularities of different type of tissues. Towards this direction, in this paper we present a novel pathloss and scattering models for in-to-out-of OWC links. Specifically, we derive extract analytical expressions that accurately describe the absorption of the five main tissues’ constituents, namely fat, water, melanin, oxygenated and de-oxygenated blood. Moreover, we formulate a model for the calculation of the absorption coefficient of any generic biological tissue. Next, by incorporating the impact of scattering in the aforementioned model we formulate the complete pathloss model. The developed theoretical framework is verified by means of comparisons between the estimated pathloss and experimental measurements from independent research works. Finally, we illustrate the accuracy of the theoretical framework in estimating the optical properties of any generic tissue based on its constitution. The extracted channel model is capable of boosting the design of optimized communication protocols for a plethora of biomedical applications.

In this work, we explore the intrinsic disorder status of the three members of the synuclein family of proteins - α-, β-, and γ-synucleins. We also analyzed the peculiarities of the amino acid sequences and modeled 3D structures of the human synuclein family members to find potential effects of pathological mutations. Furthermore, we conducted a comparative sequence-based analysis of the synuclein proteins from various evolutionary distant species and evaluated their levels of intrinsic disorder using a set of commonly used bioinformatics tools. Next, we conducted a detailed functional disorder analysis of the proteins in the interactomes of the human synuclein family members using various web-based disorder analysis and prediction tools, such as RIDAO, D2P2 and FuzDrop. We identify that the interactome of human α-synuclein has relatively higher levels of intrinsic disorder, as compared to the interactomes of human β- and γ- synucleins. These observations highlight the critical importance of intrinsic disorder of human α-synuclein and its interactors in neuronal processes as compared to other proteins of the synuclein family.

Reinventing approved therapeutic proteins for a new dose, a new formulation, a new route of administration, an improved safety profile, a new indication, or a new conjugate with a drug or a radioactive source is a creative approach to benefit from the billions spent on developing new therapeutic proteins. These new opportunities were created only recently with the arrival of AI/ML tools and high throughput screening technologies. Furthermore, the complex nature of proteins offers mining opportunities that are not possible with chemical drugs; bringing in newer therapies without spending billions makes this path highly lucrative financially while serving the dire needs of humanity. This paper analyses several practical reinventing approaches and suggests regulatory strategies to reduce development costs significantly. This should enable the entry of hundreds of new therapies at affordable costs.

A plenty of theories on the origin of genetic codes have been proposed so far, yet all ignored the energetic driving force, its relation to the biochemical system, and most importantly, the missing “matchmaker” between proteins and nucleic acids. Here, a new hypothesis is proposed, according to which ATP is at the origin of the primordial genetic code by driving the coevolution of the genetic code with the pristine biochemical system. This hypothesis aims to show how the genetic code was produced e.g. by photochemical reactions in a protocell that derived from a lipid vesicle enclosing various life’s building blocks (e.g. nucleotides and peptides). At extant cell, ATP is the only energetic product of photosynthesis, and is at the energetic heart of the biochemical systems. ATP could energetically form and elongate chains of both polynucleotides and polypeptides, thus acting a “matchmaker” between these two bio-polymers and eventually mediating precellular biochemical innovation from energy transformation to informatization. ATP was not the only one that could drive the formation of polynucleotides and polypeptides, but favored by precellular selection. The protocell innovated a photosynthesis system to produce ATP efficiently and regularly with the aids of proteins and RNA/DNA. The completion of permanently recording the genetic information by DNA marked the dawn of cellular life operated by Darwinian evolution. The ATP hypothesis assumes or supports the photochemical origin of life, shedding light on the origins of both photosynthetic and biochemical systems, which remains largely unknown thus far. Based on ATP hypothesis, virus (like the new coronavirus) could not be the earliest life on Earth, as it has neither biochemical systems nor lipid bilayer membrane that provided relatively isolated environment for the development of protobiochemical reactions, although it owns the genetic code of a cellular life. Virus could not be a bridge between life and non-life, but is an anti-life substance, as it depletes cellular material for its own replication, and then spreads by destroying the host cells. It can be imagined that if cellular life are completely wiped out by the virus, the complete destruction of life on Earth would be inevitable.

Dictyostelium discoideum is gaining increasing attention as a model organism for the study of calcium binding and calmodulin function in basic biological events as well as human diseases. After a short overview of calcium-binding proteins, the structure of Dictyostelium calmodulin and the conformational changes effected by calcium ion binding to its four EF hands is compared to its human counterpart, emphasizing the highly conserved nature of this central regulatory protein. The calcium-dependent and -independent motifs involved in calmodulin binding to target proteins are discussed with examples of the diversity of calmodulin binding proteins that have been studied in this amoebozoan. The methods used to identify and characterize calmodulin binding proteins is covered followed by the ways Dictyostelium is currently being used as a system to study several neurodegenerative diseases and how it could serve as a model for studying calmodulinopathies such as those associated with specific types of heart arrythmia. Because of its rapid developmental cycles, its genetic tractability, and a richly endowed stock center, Dictyostelium is in a position to become a leader in the field of calmodulin research.

HD-Zip proteins are unique to plants, and contain a homeodomain closely linked to a leucine zipper motif, which are involved in dimerization and DNA binding. Based on homology in the HD-Zip domain, gene structure and the presence of additional motifs, HD-Zips are divided into four families, HD-Zip I–IV. Phylogenetic and bioinformatics analysis of HD-Zip genes using transcriptomic and genomic datasets from a wide range of plant species indicate that the HD-Zip protein class was already present in green algae. Later, HD-Zips experienced multiple duplication events that promoted neo- and sub-functionalizations. HD-Zip proteins are known to control key developmental and environmental responses, and a growing body of evidence indicates a strict link between members of the HD-Zip II and III families and the auxin machineries. Interactions of HD-Zip proteins with other hormones such as brassinolide and cytokinin have also been described. However, it is striking that among the genes regulated by REV, a HD-Zip III protein playing a key role in apical development, are genes that mediate ABA signaling. Furthermore, HAT1 and HAT3, two HD-Zip II proteins involved in key developmental processes, repress ABA biosynthesis and signaling, indicating an essential role of these factors in adjusting development to changing environment.

The Casiquiare River is a natural channel that connects two of the greatest rivers in the world, the Orinoco and the Amazon in the South American Continent. The aim of this paper is to present a review and synthesis of the hydrological and sedimentological knowledge of the Casiquiare River, including the first hydro-sedimentary balance of the Casiquiare fluvial system conducted at the bifurcation and at the mouth on September 9-12, 2000, during the expedition ‘Humboldt-Amazonia 2000’. Bathymetric, flow discharge and physico-chemical measurements were made at the inlet and at the outlet of the Casiquiare Channel. The main conclusions of this study indicate that Casiquiare is taking a significant proportion of flow (20 to 30%) from the Upper Orinoco basin to the Amazon basin. Throughout its 356 km-course, this chameleon channel undergoes significant morphological, hydrological and bio-geochemical variations between the inlet and the outlet, whose most visible witnesses are the increase in its width (3 to 4 times), flow (7 to 9 times) and its change in water color (white to black water), under the influence of tributaries coming from vast forest plains.

Pore fluid pressure is very important to the generation, migration and accumulation of petroleum. The previous studies indicate that the Chezhen sag region is typically characterized by pore fluid overpressure (the difference between pore fluid pressure and hydrostatic pressure). To date, the formation mechanism of pore overpressure and the accumulation regularity of “upper source-lower reservoir” type in this region remains unknown. In order to investigate these problems, a 2-D finite element model is established with regards to the fluid-solid coupling in Chegu 25 block of Chezhen depression, fully considering the existing seismic, logging data and regional tectonic stress environment. Meanwhile, we calculate the abnormal overpressure generated at the source rock during hydrocarbon generation and the process of hydrocarbon migration and accumulation along the faults, analyzing the dynamic conditions of hydrocarbon downward accumulation. The results show that overpressure can accelerate migration of hydrocarbon and improve the efficiency of hydrocarbon accumulation. However, when the overpressure is too large, tensile fractures and shear fractures may occur, resulting in hydrocarbon dissipation, and changing the results of oil and gas accumulation. The overpressure at the source rock is mainly caused by hydrocarbon generation, while the overpressure at the reservoir is primarily created by unbalanced compaction. As the dominant channel of hydrocarbon migration, overpressure will change the direction and path of hydrocarbon migration in the fault. Therefore, the “upper source-lower reservoir” hydrocarbon accumulation model is strongly explained by the high permeability of faults and the presence overpressure. In summary, the simulated overpressure results are in good agreement with the mud weight equivalent overpressure and the drill stem tests (DSTs).

Metabolic and ionic changes during ischaemia predispose the heart to the damaging effects of reperfusion. Such changes and the resulting injury differ between immature and adult heart. Therefore, cardioprotective strategies for adults need to be tested in immature heart. We have recently shown that simultaneous activation of PKA and EPAC confers marked cardioprotection in adult hearts. The aim of this study is to investigate the efficacy of this intervention in immature hearts and determine whether the mitochondrial permeability transition pore (MPTP) is involved. Isolated perfused Langendorff hearts from both adult and immature rats were exposed to global ischaemia and reperfusion injury (I/R) following control perfusion or perfusion after an equilibra-tion period with activators of PKA and/or EPAC. Functional outcome and reperfusion injury were measured and in parallel, mitochondria were isolated following 5 min reperfusion to determine whether cardioprotective interventions involved changes in MPTP opening behaviour. Perfusion for 5 minutes preceding ischaemia of injury- matched adult and immature hearts with 5 µM 8-Br (8-Br-cAMP-AM), an activator of both PKA and EPAC, led to significant reduction in post-reperfusion CK release and infarct size. Perfusion with this agent also led to a reduction in MPTP opening propensity in both adult and immature hearts. These data show that immature hearts are innately more resistant to I/R injury than adults, and that this is due to a reduced ten-dency to MPTP opening following reperfusion. Further, simultaneous stimulation of PKA & EPAC causes cardioprotection which is additive to the innate resistance.

This is a brief critique of the functions—particularly olfactory functions—specified for the “Chemosensory Protein” (CSPs) molecule family. On the basis of these proteins’ presence in the sensory antennal lymph of locusts, odor chemosensory ligand binding functions have been hypothesized. According to this hypothesis, the entire protein molecule superfamily is referred to as “CSPs”. However, new information and developments in the field of CSP molecular research, such as the expression of CSP genes in the gut, brain, fat body, epidermis, and pheromone gland, as well as gene expression profiling from most early developmental stages—that is, CSP expression well in advance of the appearance of chemical sense nerve cells—strongly suggest that the protein molecule has other roles that are unrelated to chemosensing. Moreover, CSPs are found in bacterial microbial prokaryote organisms in addition to insects. Thus, we examine the molecule’s name, definition, RNA editing, protein structure, lipid binding properties, DNA interaction, and evolutionary characteristics in brief before referring to this protein family as “Chemosensory Proteins”. This article tries to compel and discuss the most recent information as a way to rename this protein family. Because of its highly conserved molecular distinctive feature (four adjacent cysteines), we propose renaming “CSPs” as “4CSPs” (4 Cysteines Soluble Proteins).

The purpose of this paper is to propose a novel transfer learning regularization method based on knowledge distillation. Recently, transfer learning methods have been used in various fields. However, the problems such as knowledge loss still occur during the process of transfer learning to a new target dataset. To solve these problems, there are various regularization methods based on knowledge distillation techniques. In this paper, we propose a transfer learning regularization method based on feature map alignment used in the field of knowledge distillation. The proposed method is composed of two attention based submodules: self-pixel attention (SPA) and global channel attention (GCA). The self-pixel attention submodule utilizes both the feature maps of the source and target models, so that it provides an opportunity to jointly consider the features of the target and the knowledge of the source. The global channel attention submodule determines the importance of channels through all layers, unlike the existing methods that calculate these only within a single layer. Accordingly, transfer learning regularization is performed by considering both the internal of each single layer and the depth of the entire layer. Consequently, the proposed method using both of these submodules showed overall improved classification accuracy than the existing methods in classification experiments on commonly used dataset.

This paper addresses the problem of low accuracy of conventional channel estimation and signal detection in complex fields like mines; and the problem of replacing the deep receiver at the receiver side with a deep neural network requires a large amount of data for training and slow training time. Combining the receiver side with traditional communication knowledge, a channel estimation and signal detection method based on the joint ReEsNet and SDRNet under the mine is proposed. The detailed step is to use ReEsNet network for interpolation of conventional channel estimation. Then, on the basis of ReEsNet, the output data is channel equalized and pilots removed, and the previously processed data is input to SDRNet to perform signal recovery. In the complex mine environment, the MSE values are 2e-2 for LS, 6e-3 for MMSE, and 8.44e-5 for ReEsNet at the 1500th sample data for interpolation compared to the conventional channel estimation. the MSE of ReEsNet is the smallest and is closer to the real channel estimation. Compared with the proposed joint channel estimation and signal detection methods, fewer trainable parameters reduce 97% of the parameters compared to CCRNet and 84% of the parameters compared to CNNNet; their detection results, however, are not very different.

After cut by basecutter, sugarcane stalks are carried to a chopper by the basecutter and the feeding/conveying rollers train of harvester. However, the conventional feeding/conveying channels of sugarcane chopper harvesters, when harvesting seriously lodged sugarcane, have numerous drawbacks, including easy clogging, and poor adaptability. In order to resolve these problems, a novel design and layout method of feeding/conveying and chopping channel are proposed in the paper. And a chopper centrally-mounted channel is designed for a sugarcane chopper harvester as well, which has been implemented in the HN4GDL-91 harvester. The proposed channel consists of a feeding/conveying rollers train, a chopper, and a billet conveying device. By mounting the chopper between the feeding/conveying rollers train and the billets conveying device, the harvester can avoid the chopper chopping back the billets, thus improving the harvest quality. The feeding/conveying rollers train is designed with only a pair of feeding rollers and a pair of conveying rollers, achieving a short channel path. Moreover, the structure of the basecutter and the mechanism carrying stalks to feeding rollers are studied via theoretical analysis and tests. The relationship between the basecutter and the chopper centrally-mounted channel is also conducted in systematic analysis. The results of the theoretical analysis show that the inclination angle of the disc of basecutter should be 2° greater than the angle of the feeding conveying channel (both angles are from the horizontal plane). The inclination angle of the disc of basecutter should go from 10° to 15°. A field experiment with four factors and three levels indicates that the field loss rate is 2.45%, the feed quantity is 16.66 kg/s, and the qualified rate of the billets is 98.02%, while the number of sugarcane stalks in a clump, the ground speed of harvester the rotational speed of the chopper, and the rotational speed of feeding/conveying roller are 10, 1.09 m/s, 390 r/min, and 230 r/min, respectively. It is concluded that the proposed chopper centrally-mounted channel could improve the conveying and harvesting performance significantly.

EMG analysis is becoming increasingly important in many research and clinical applications, including muscle fatigue detection, control of robotic mechanisms and prostheses, clinical diagnosis of neuromuscular diseases and quantification of force. However, electromyographic signals can be contaminated by various types of noise, interference and artifacts, which can lead to misinterpretation of the data acquired using this method. Even assuming best practices, the collected signal may still be altered by such contaminants. The aim of this paper is to review methods employed to reduce contamination of single channel EMG signals. This review is limited to methods performed directly on the measured EMG signal and those that allow total reconstruction of the EMG signal. Subtraction methods used in the time domain, denoising methods performed after signal decomposition and hybrid methods are assessed. It is defended that individual methods may be more or less suitable for a particular application depending on contaminant(s) present in the signal and on the specific requirements of the application.

Deep convolutional neural network (CNN) has shown their great advantages in the single image deraining task. However, most existing CNN-based single image deraining methods still suffer from residual rain streaks and details lost. In this paper, we propose a deep neural network including the Multi-scale feature extraction module and the channel attention module, which are embed in the feature extraction sub-network and the rain removal sub-network respectively. In the feature extraction sub-network, the Multi-scale feature extraction module is constructed by a Multi-layer Laplacian pyramid, and is then integrated multi-scale feature maps by a feature fusion module. In the rain removal sub-network, the channel attention module, which assigns different weights to the different channels, is introduced for preserving image details. Experimental results on visually and quantitatively comparison demonstrate that the proposed method performs favorably against other state-of-the-art approaches

Purpose: The purpose of this study was to evaluate the dosimetric impact of multiple channels compared to a single channel in high dose rate (HDR) vaginal cuff brachytherapy (VCBT). Methods and materials: Sample plans of HDR VCBT from both single and multiple channel cylinders at 2.5, 3.0 and 3.5 cm in diameter were created and analyzed. The doses were prescribed either at the 0.5 cm depth with 5.5 Gy for 4 fractions or at the cylinder surface with 8.8 Gy for 4 frac¬tions, in various treatment lengths ranging from 3 to 8 cm. A 0.5 cm ring target volume called PTV_Eval was contoured for each plan and served as the target volume for dosimetric evaluation. Mean doses and the doses covering 90% (D90), 10% (D10), and 5% (D5) of PTV_Eval were calculated and compared. The same treatment lengths, same prescription regimens, same target volume contouring and same plan evaluation methods were repeated for the similar size single channel and multiple channel cylinders. Results: The mean doses of both regimens with the multi-channel cases (6.3 to 7.1 Gy) were comparable to single channel ones (6.4 and 7.5 Gy). The ranges of D90, D10 and D5 were from 3.654 to 5.04 Gy, 8.44 to 10.08 Gy and 8.84 to 10.86 Gy in the multi-channel cases, but from 5.36 to 5.76 Gy, 7.40 to 9.97 Gy and 8.16 to 11.93 Gy in the single channel cases, respectively. Conclusion: The single channel and multiple-channel cylinder deliver a similar mean dose, but with marked heterogeneity in D90, D5 and D10 for the same prescription dose and target volume. Multi-channel cylinders adequately cover the target volume, but given the heterogeneity, increased treatment time and cost are best suited for asymmetric target volumes.

Rett syndrome (RTT) is mainly caused by mutations in methyl CpG-binding protein 2, cyclin-dependent kinase-like 5, or forkhead box protein G1. These RTT-causing proteins harbor an intrinsically disordered region (IDR) whose conformation exhibits spatiotemporal heterogeneity, which not only confer versatility to the protein, but also implicates them in diseases. The IDR generally evolves more rapidly than an ordered structure. In this study, we examined the relationship between pathogenic RTT-associated point mutations in RTT-causing proteins and the evolutionary dynamics of sequence features including structural order–disorder, phosphorylation sites, and evolutionary rates. We also analyzed the molecular properties and evolution of proteins that interact with RTT-causing proteins in terms of phylogenetic profiles, tissue specificity, subcellular localization, expression level, and functions. The results indicate that constrained IDRs may function by forming contacts with other regions in the protein sequence causing pathogenic missense mutations likely to arise in the rapidly evolving IDR and affect molecular networks, leading to disease. The results also provide novel insights into the genetic basis for RTT and the evolution of the neocortex in higher vertebrates.

It is widely reported that the mitochondrial membrane potential, ∆Ψm, is reduced in aging animals. It was recently suggested that the lower ∆Ψm in aged animals modulate mitochondrial bioenergetics and that this effect is a major cause of aging since artificially increased ∆Ψm in C. elegans increased lifespan. Here I review, critically, studies that reported reduction of ∆Ψm in aged animals, including worms, and conclude that many of these observations are best interpreted as evidence that the fraction of depolarized mitochondria is increased in aged cells because of the enhanced activation of the mitochondrial Permeability Transition Pore, mPTP. Activation of the voltage-gated mPTP depolarizes the mitochondria, inhibits oxidative phosphorylation, releases large amounts of calcium and mROS, and depletes cellular NAD+, thus accelerating degenerative diseases and aging. Since the inhibition of mPTP was shown to restore ∆Ψm and retard aging, the reported lifespan extension by artificially generated ∆Ψm in C. elegans is best explained by inhibition of the voltage-gated mPTP. Similarly, the reported activation of the mitochondrial Unfolded Protein Response by reduction of ∆Ψm, and the reported preservation of ∆Ψm in dietary restriction treatment in C. elegans are best explained as a resulting from activation or inhibition of the voltage-gated mPTP, respectively.

In our previous works we have proposed design equations that can predict with reasonable accuracy the transition point from homogeneous to heterogeneous regime as well as the gas holdup and the mean Sauter diameter at the homogeneous regime. The validity of the proposed correlations was checked with data obtained using different geometrical configurations and several Newtonian and non-Newtonian liquids as well as the addition of surfactants. However, in all the experiments the gas phase was atmospheric air. This work investigates the effect of gas phase properties by conducting experiments employing various gases (i.e., air, CO₂, He) that cover a wide range of physical property values. Experiments revealed that only the use of low-density gas (He) has a measurable effect on bubble column performance. More precisely, when the low-density gas (He) is employed, the transition point shifts to higher gas flow rates and the gas holdup decreases, a fact attributed to the lower momentum force exerted by the gas. In view of the new data, the proposed correlations have been slightly modified to include the effect of gas phase properties and it is found that they can predict the aforementioned quantities with an accuracy of ±15%. It has been also proved that CFD simulations are an accurate means for assessing the flow characteristics inside a bubble column.

A comprehensive study of the interactions of human serum albumin (HSA) and α-1-acid glycoprotein (AAG) with two isoquinoline alkaloids: allocryptopine (ACP) and protopine (PP) was performed. The UV-Vis spectroscopy, molecular docking, competitive binding assays, and circular dichroism (CD) spectroscopy were used for the investigations. The results showed that ACP and PP form spontaneous and stable complexes with HSA and AAG, with ACP displaying a stronger affinity towards both proteins. Molecular docking studies showed also revealed the preferential binding of ACP and PP to specific sites within HSA, with site 2 (IIIA) being identified as the favored location for both alkaloids. This was supported by competitive binding assays using markers specific to HSA's drug binding sites. Similarly, for AAG, a decrease in fluorescence intensity upon addition of the alkaloids to AAG/ Quinaldine Red (QR) complexes indicated the replacement of the marker by the alkaloids, with ACP showing a greater extent of replacement than PP. CD spectroscopy showed that the proteins’ structures remained largely unchanged suggesting that the formation of complexes did not significantly perturb the overall spatial configuration of these macromolecules. These findings are crucial for advancing the knowledge on the natural products-protein interactions and the future design of isoquinoline alkaloid-based therapeutics.

Herpesviridae is a family of enveloped double-stranded DNA viruses that cause a wide range of diseases in hosts. Among the various components of herpesvirus particles, tegument proteins residing between the envelop and nucleocapsid play crucial roles in viral replication, immune evasion, and modulation of host cellular pathways. Understanding the three-dimensional structure of herpesvirus tegument proteins help to reveal the molecular mechanism underlying the crosstalk with other viral and cellular components, and thus is crucial for the investigation of their biological and pathological functions. In this review, we summarize the current knowledge of the structural features of herpesvirus tegument proteins, highlighting the structure-based functional implications, including the potential as targets for antiviral drug development.

Healthcare faces a major problem with the increased emergence of antimicrobial resistance due to the over-prescription of antibiotics. This causes dysbiosis and major disruption of the gut microbiome, leading to the development of intestinal diseases, abnormalities in the regulation of immune responses, malfunctioning of entero-endocrine signaling, and an imbalance in communication with the central nervous system (CNS). Bacteriophages may provide a solution to the treatment of bacterial infections given their specificity. This approach increased rapidly over the last ten years, because of the rapid rise of multi-drug-resistant bacteria worldwide coupled with a decline in the development and production of novel antibacterial agents. Eradication of multidrug-resistant bacteria is often only possible with bacteriophage treatment. Phage proteins are used to stimulate immune responses against specific pathogens, improve antibiotic susceptibility, prevent biofilm formation, and characterize bacterial pathogens. This review discusses the therapeutic potential of bacteriophage-derived proteins.

A major obstacle faced by nanopore-based polymer sequencing and analysis is the high speed of translocation of an analyte (nucleotide, DNA, amino acid (AA), peptide) through the pore; the rate currently exceeds available detector bandwidth. Except for one method that uses an enzyme ratchet to sequence DNA, attempts to resolve the problem satisfactorily have been largely unsuccessful. Here a counterintuitive method based on reversing the pore voltage, and, with some analytes, increasing their mobility, is described. A simplified Fokker-Planck model shows a significant increase in translocation times for single nucleotides and AAs (up from ~10 ns to ~1 ms). More realistic simulations show that with a bi-level positive-negative pore voltage profile all four nucleotides in DNA (dAMP, dTMP, dCMP, and dGMP) and the 20 proteinogenic amino acids can be trapped inside the pore long enough for detection with bandwidths of ~1-10 Khz.

(1) Background: The Gárdos channel (KCNN4) and Piezo1 are the best-known ion channels in the red blood cell (RBC) membrane. Nevertheless, the quantitative electrophysiological behavior of RBCs and its heterogeneity are still not completely understood.; (2) Methods: Here we use state-of-the-art biochemical methods to probe for the abundance of the channels in RBCs. Furthermore, we utilize automated patch-clamp, based on planar chips, to compare the activity of the two channels in reticulocytes and mature RBCs. Besides this characterization, we performed membrane potential measurements to demonstrate the effect of channel activity and interplay on the RBC properties.; (3) Results: Both, Gárdos channel and Piezo1, albeit their average copy number of activatable channels per cell is in the single digit range, can be detected by transcriptome analysis of reticulocytes. Proteomics analysis of RBCs could only detect Piezo1 but not the Gárdos channel. Furthermore, they can be reliably measured in the whole-cell configuration of the patch-clamp method. While for the Gárdos channel the activity is higher in reticulocytes compared to mature RBCs, for Piezo1 the tendency is the opposite. While the interplay between Piezo1 and Gárdos channel cannot be followed using the patch-clamp measurements, it could be proved based on membrane potential measurements in populations of intact RBCs.; (4) Conclusions: We discuss the Gárdos channel and Piezo1 abundance, interdependencies and interactions in the context of their proposed physiological and pathophysiological functions, which are the passing of small constrictions, e.g., in the spleen, and their active participation in blood clot formation and thrombosis.

Data obtained by Direct Numerical Simulations (DNS) of pressure-driven turbulent channel flow are studied in the range 180 ≤ Reτ≤ 10,000. Reynolds number effects on the Mean Velocity Profile (MVP) and second order statistics are analyzed with a view of finding logarithmic behavior in the overlap region or even further from the wall, well in the boundary layer’s outer region. Values of Kármán constant for the MVPs and the Townsend-Perry constants for the streamwise and spanwise fluctuation variances are determined for the Reynolds numbers considered. A data-driven model of the MVP, proposed and validated for zero pressure gradient flow over a flat plate, is employed for pressure-driven channel flow by appropriately adjusting Coles’ strength of the wake function parameter, Π. There is excellent agreement between the analytic model predictions of MVP and the DNS-computed MVP as well as of the Reynolds shear stress profile. The skin friction coefficient Cf is calculated analytically. The agreement between the analytical model predictions and the DNS-based computed discrete values of Cf is excellent.

Our study provides guidelines on how to build long-term customer relationship in the non-contract mechanism context. More specifically, the findings show that special, social, and core benefits influence calculative commitment, and operational and special benefits influence affective commitment. This study also supports that calculative and affective commitment play a crucial role in understanding multi-channel agencies’ loyalty. In sum, this study revealed that calculative and affective commitment can be considered as partial or full mediators in the relationship between RBs (relational benefits) and loyalty. This study not only contributed to the existing SET (social exchange theory) and RBs paradigm but also provided practical implications for food distribution management.

Microcombs provide a potential compact and efficient light source for multi-Terabit-per-second optical superchannels. However, as the bandwidth of these multi-wavelength light sources is increased, this can result in low per-line power. Optical amplifiers can be used to overcome power limitations, but the accompanying spontaneous optical noise can degrade performance in optical systems. To overcome this issue, we propose wideband noise reduction for comb lines using a high-Q microring resonator, whose resonances align with comb lines. When applying the proposed distillation to a superchannel system with 18 Gbaud, 64-QAM sub-channels in a > 10 Tb/s optical superchannel, we find that noise-corrupted comb lines can reduce the optical signal-to-noise ratio required for the comb by ~ 9 dB when used as optical carriers at the transmitter side, and by ~ 12 dB when used as a local oscillator at the receiver side.