Worm Model Research Articles

Meshing theory and contact analysis of double enveloping hourglass worm drive with planar generatrix

The meshing and limit equations of worm drive usually have strong nonlinearities such as multiple solutions, solution nonexistence and equation singularity. Meanwhile, the tooth surfaces of worm drive are in nonconforming line contact, which often requires mesh refinement of contact region for the loaded contact analysis. These two challenges cause that the modeling of worm drive heavily relies on manual adjustment and the loaded contact analysis of worm drive is still rare especially when edge contact and assembly error are concerned. Focusing on the double enveloping hourglass worm (DEHW) drive with planar generatrix, this work presents procedures to solve meshing and limit equations with global convergence. The instantaneous contact line, meshing limit line, curvature interference limit line and tooth surface grid discretization are adaptively generated, without manual trial or adjustment. On the basis of adaptive mesh refinement of tooth surface, the mortar virtual element method is adopted for loaded contact analysis of DEHW drive with edge contact and center distance error. Under sliding friction, the discrete system of governing equalities and inequalities is solved by semi-smooth Newton algorithm after constraint condensation. Numerical results for meshing theory and loaded contact analysis of DEHW drive with planar generatrix are discussed.

EYA protein complex is required for Wntless retrograde trafficking from endosomes to Golgi

Retrograde transport of WLS (Wntless) from endosomes to trans-Golgi network (TGN) is required for efficient Wnt secretion during development. However, the molecular players connecting endosomes to TGN during WLS trafficking are limited. Here, we identified a role for Eyes Absent (EYA) proteins during retrograde trafficking of WLS to TGN in human cell lines. By using worm, fly, and zebrafish models, we found that the EYA-secretory carrier-associated membrane protein 3 (SCAMP3) axis is evolved in vertebrates. EYAs form a complex and interact with retromer on early endosomes. Retromer-bound EYA complex recruits SCAMP3 to endosomes, which is necessary for the fusion of WLS-containing endosomes to TGN. Loss of EYA complex or SCAMP3 leads to defective transport of WLS to TGN and failed Wnt secretion. EYA mutations found in patients with hearing loss form a dysfunctional EYA-retromer complex that fails to activate Wnt signaling. These findings identify the EYA complex as a component of retrograde trafficking of WLS from the endosome to TGN.

The anti-leprosy drug clofazimine reduces polyQ toxicity through activation of PPARγ

PolyQ diseases are autosomal dominant neurodegenerative disorders caused by the expansion of CAG repeats. While of slow progression, these diseases are ultimately fatal and lack effective therapies. A high-throughput chemical screen was conducted to identify drugs that lower the toxicity of a protein containing the first exon of Huntington's disease (HD) protein huntingtin (HTT) harbouring 94 glutamines (Htt-Q94). Candidate drugs were tested in a wide range of invitro and invivo models of polyQ toxicity. The chemical screen identified the anti-leprosy drug clofazimine as a hit, which was subsequently validated in several invitro models. Computational analyses of transcriptional signatures revealed that the effect of clofazimine was due to the stimulation of mitochondrial biogenesis by peroxisome proliferator-activated receptor gamma (PPARγ). In agreement with this, clofazimine rescued mitochondrial dysfunction triggered by Htt-Q94 expression. Importantly, clofazimine also limited polyQ toxicity in developing zebrafish and neuron-specific worm models of polyQ disease. Our results support the potential of repurposing the antimicrobial drug clofazimine for the treatment of polyQ diseases. A full list of funding sources can be found in the acknowledgments section.

Structure elucidation and antioxidant activity of a polysaccharide from Penthorum chinense Pursh

Penthorum chinense Pursh is a traditional Miao medicine, mainly used in the treatment of liver diseases. In this study, an acidic heteropolysaccharide PCPP was isolated from P. chinense with an average molecular weight of 14.96 kDa. PCPP contained arabinogalactan and homogalacturonan segments, which is formed by 4-Galp-(1 → 5)-Araf-1 and 3,6-Galp-(1 → 6)-Galp-1,3 glycosidic linkage. A variety of side chains, including t-Glcp-(1 → 4)-Glcp-(1 → 4)-GlcpA-1, t-Xylp-(1→, and 2-Manp-(1 → 4)-GalpA-1,3 linked to the O-3 and O-6 of 3,6-Galp. The antioxidant activity measurement in three models demonstrated that PCPP exhibited ROS scavenging capacity, antioxidant ability in the cellular model, enhancement of oxidative stress resistance, and healthspan-promoting effect in the worm model. These results provided the theoretical fundament of PCPP as a potential natural antioxidant.

PHARMACOLOGIC AMPK ACTIVATION IMPROVES HEALTHSPAN AND LIFESPAN IN NORMAL AND PREMATURE AGING MODELS

Abstract Cockayne Syndrome (CS) is a rare autosomal recessive childhood disease, caused by mutations in CSA (ERCC8) or CSB (ERCC6) genes leading to defective DNA damage repair. CS characteristics include UV sensitivity and premature aging. Deficiencies in CSA or CSB may lead to impaired AMP-activated protein kinase (AMPK) activation. Notably, AMPK-activating interventions have shown promise in preclinical CS mouse models. We tested whether MK8722, an AMPK activator, could mitigate CS phenotypes in a C. elegans model. Our preliminary data show that MK-8722 increases lifespan in wild-type and CS worm model. We also tested the effect of MK-8722 on brood size as a fitness parameter and showed that it does not change the total brood size. We also showed that treating aged mice with MK-8722 improves multiple measures of healthspan including body composition, grip strength and age-associated inflammation. These data suggest that AMPK activation may be a promising therapeutic avenue for both normal and CS-associated aging phenotypes

Ethyl Isothiocyanate as a Novel Antifungal Agent Against Candida albicans.

In the recent years, occurrence of candidiasis has increased drastically which leads to significant mortality and morbidity mainly in immune compromised patients. Glucosinolate(GLS) derivatives are reported to have antifungal activities. Ethyl isothiocyanate (EITC) and its antifungal activity and mechanism of action is still unclear against Candida albicans. The present workwas designed to get a mechanistic insight in to the anti-Candida efficacy of EITC through invitro and in vivo studies. EITC inhibited C. albicans planktonic growth at 0.5mg/ml and virulence factors like yeast to hyphal form morphogenesis (0.0312mg/ml), adhesion to polystyrene surface (0.0312mg/ml) and biofilm formation (developing biofilm at 2mg/ml and mature biofilm at 0.5mg/ml) effectively. EITC blocked ergosterol biosynthesis and arrested C. albicans cells at S-phase. EITC caused ROS-dependent cellular death and nuclear or DNA fragmentation. EITC at 0.0312mg/ml concentration regulated the expression of genes involved in the signal transduction pathway and inhibited yeast to hyphal form morphogenesis by upregulating TUP1, MIG1, and NRG1 by 3.10, 5.84 and 2.64-fold, respectively and downregulating PDE2 and CEK1 genes by 15.38 and 2.10-fold, respectively. EITC has showed haemolytic activity at 0.5mg/ml concentration. In vivo study in silk worm model showed that EITC has toxicity to C. albicans at 0.5mg/ml concentration. Thus, from present study we conclude that EITC has antifungal activity and to reduce its MIC and toxicity, combination study with other antifungal drugs need to be done. EITC and its combinations might be used as alternative therapeutics for the prevention and treatment of C. albicans infections.

Theoretical modeling and transmission characteristics analysis of a novel double-roller hourglass worm drive based on enveloping principle

Traditional planar double-enveloping hourglass worm pairs have the characteristics such as the strong bearing capacity, high transmission efficiency and long life-span. However, the high relative sliding velocity and the serious agglutination or abrasion may also occur at the contact point on tooth surfaces. In this paper, a novel type of double-roller hourglass worm pair is proposed and analyzed, wherein, the worm part adopts from the planar double-enveloping worm pair, the corresponding meshing tooth surface of worm gear is replaced by two rows of cylinder rollers for reducing friction and enhancing meshing efficiency. That is, the original meshing tooth surfaces in worm gear are replaced by the common tangent plane of rollers to form a special type of meshing drive, the original line-contact form between tooth surfaces was changed to point-contact so that the sliding friction was transformed into rolling friction, and the meshing efficiency can be greatly improved. The theoretical model of double-roller hourglass worm pair was established based on spatial enveloping principle, the meshing equation and tooth surface equations were derived. The solid models of worm and gear were established and assembled. The parameters of enveloping surface angle, roller radius and friction coefficient, which affecting relative motion velocity at meshing contact point and efficiency during the whole transmission process was analyzed and discussed systematically. The results showed that comparing to the traditional worm pair, the roller’s rotation greatly reduced the relative sliding velocity and improved meshing efficiency at the contact point in this double-roller hourglass worm pair.

Efficacy of Azadirachta indica in the Treatment of Gastrointestinal Helminthiasis

The study was carried out to assess the anthelminthic efficacy of Azadirachta indica commonly known as Neem (Dogoyaro). The phytochemical components of the leaf extract was accessed using Gas Chromatography Mass Spectrometry and the efficacy was carried out in vitro and in vivo using Toxocara canis (as worm model) of dogs. Twenty peaks of compounds were revealed in the GS-MS chromatogram, with Hexadecanoic acid which is saddled with anthelminthic effect as one of its major constituents. In the in vitro study, the lethal concentration was 92.48ml/mg at 6hrs. Percentage egg reduction of 76.2% and 83.9% from the Faecal Egg Count (FEC) at LC25 and LC50 respectively was recorded for the in vivo study. The overall blood count of all the puppies used for the experiment were 4.46 X 106µL for RBC, 31.32% for PCV and 11.23 X 103for WBC. Puppies treated with Azadirachta indica leaf extract showed minimal alteration of the three heamatological parameters (WBC, PCV and RBC) analyzed compared to the uninfected control group and group treated with Mbendazole. This indicates that Azadirachta indica leaf extract is effective in the treatment of gastrointestinal helminthiasis and also further investigations are recommended as it may be useful in the treatment of other diseases.

Back to the future through the wormhole: Caenorhabditis elegans as a preclinical model.

On the 15th Anniversary of Disease Models & Mechanisms as a trailblazing venue for the dissemination of discoveries pertaining to human health involving model systems, we celebrate the journey of this journal, as mirrored through the evolution of research using the nematode roundworm, Caenorhabditis elegans. Driven by the exponential growth of genomic data, worms have advanced from a basic research tool to precise and elegant models for disease and have yielded substantive insights into numerous human disorders. A harbinger of functional genomic analysis since the inception of RNA interference screening, the directed application of C. elegans for identification of disease-modifying factors has revealed new pathways and therapeutic targets to accelerate translational outcomes. Together with advances in gene editing, worm models are now ushering in the era of precision medicine with characteristic expedience.

Deletion of SERF2 in mice delays embryonic development and alters amyloid deposit structure in the brain.

In age-related neurodegenerative diseases, like Alzheimer's and Parkinson's, disease-specific proteins become aggregation-prone and form amyloid-like deposits. Depletion of SERF proteins ameliorates this toxic process in worm and human cell models for diseases. Whether SERF modifies amyloid pathology in mammalian brain, however, has remained unknown. Here, we generated conditional Serf2 knockout mice and found that full-body deletion of Serf2 delayed embryonic development, causing premature birth and perinatal lethality. Brain-specific Serf2 knockout mice, on the other hand, were viable, and showed no major behavioral or cognitive abnormalities. In a mouse model for amyloid-β aggregation, brain depletion of Serf2 altered the binding of structure-specific amyloid dyes, previously used to distinguish amyloid polymorphisms in the human brain. These results suggest that Serf2 depletion changed the structure of amyloid deposits, which was further supported by scanning transmission electron microscopy, but further study will be required to confirm this observation. Altogether, our data reveal the pleiotropic functions of SERF2 in embryonic development and in the brain and support the existence of modifying factors of amyloid deposition in mammalian brain, which offer possibilities for polymorphism-based interventions.

Establishment of Straight Profile Hourglass Worm under Virtual Reality

Virtual workpiece is widely used in dynamic simulation and can be imported into the Virtual Gear Measuring Center (VGMC) to be virtually measured. The tooth surface of hourglass worm is complicated, so the dynamic meshing performance is often improved by modification of the tooth surface. The design cycle of traditional tooth surface modification without digital virtual workpiece is long, and the dynamic meshing performance only can be judged by getting meshing spots with sample parts. In this paper, based on the direct digital modeling, the working tooth surface and the non-working tooth surface are processed respectively for the straight profile enveloping worm, and the errors introduced by the turning tool in the modeling process are eliminated. Segmental cutting and inversion methods are proposed to greatly improve the modeling efficiency. By writing software and parameterizing modeling process, the virtual workpiece model of the hourglass worm with controllable accuracy and no holes and redundant faces can be obtained conveniently and quickly. The model can improve the design efficiency and shorten the design cycle.

The alg-1 Gene Is Necessary for Orsay Virus Replication in Caenorhabditis elegans.

The establishment of the Orsay virus-Caenorhabditis elegans infection model has enabled the identification of host factors essential for virus infection. Argonautes are RNA interacting proteins evolutionary conserved in the three domains of life that are key components of small RNA pathways. C. elegans encodes 27 argonautes or argonaute-like proteins. Here, we determined that mutation of the argonaute-like gene 1, alg-1, results in a greater than 10,000-fold reduction in Orsay viral RNA levels, which could be rescued by ectopic expression of alg-1. Mutation in ain-1, a known interactor of ALG-1 and component of the RNA-induced silencing complex, also resulted in a significant reduction in Orsay virus levels. Viral RNA replication from an endogenous transgene replicon system was impaired by the lack of ALG-1, suggesting that ALG-1 plays a role during the replication stage of the virus life cycle. Orsay virus RNA levels were unaffected by mutations in the ALG-1 RNase H-like motif that ablate the slicer activity of ALG-1. These findings demonstrate a novel function of ALG-1 in promoting Orsay virus replication in C. elegans. IMPORTANCE All viruses are obligate intracellular parasites that recruit the cellular machinery of the host they infect to support their own proliferation. We used Caenorhabditis elegans and its only known infecting virus, Orsay virus, to identify host proteins relevant for virus infection. We determined that ALG-1, a protein previously known to be important in influencing worm life span and the expression levels of thousands of genes, is required for Orsay virus infection of C. elegans. This is a new function attributed to ALG-1 that was not recognized before. In humans, it has been shown that AGO2, a close relative protein to ALG-1, is essential for hepatitis C virus replication. This demonstrates that through evolution from worms to humans, some proteins have maintained similar functions, and consequently, this suggests that studying virus infection in a simple worm model has the potential to provide novel insights into strategies used by viruses to proliferate.

Using the Reactome Database.

Pathway databases provide descriptions of the roles of proteins, nucleic acids, lipids, carbohydrates, and other molecular entities within their biological cellular contexts. Pathway-centric views of these roles may allow for the discovery of unexpected functional relationships in data such as gene expression profiles and somatic mutation catalogues from tumor cells. For this reason, there is a high demand for high-quality pathway databases and their associated tools. The Reactome project (a collaboration between the Ontario Institute for Cancer Research, New York University Langone Health, the European Bioinformatics Institute, and Oregon Health & Science University) is one such pathway database. Reactome collects detailed information on biological pathways and processes in humans from the primary literature. Reactome content is manually curated, expert-authored, and peer-reviewed and spans the gamut from simple intermediate metabolism to signaling pathways and complex cellular events. This information is supplemented with likely orthologous molecular reactions in mouse, rat, zebrafish, worm, and other model organisms. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Browsing a Reactome pathway Basic Protocol 2: Exploring Reactome annotations of disease and drugs Basic Protocol 3: Finding the pathways involving a gene or protein Alternate Protocol 1: Finding the pathways involving a gene or protein using UniProtKB (SwissProt), Ensembl, or Entrez gene identifier Alternate Protocol 2: Using advanced search Basic Protocol 4: Using the Reactome pathway analysis tool to identify statistically overrepresented pathways Basic Protocol 5: Using the Reactome pathway analysis tool to overlay expression data onto Reactome pathway diagrams Basic Protocol 6: Comparing inferred model organism and human pathways using the Species Comparison tool Basic Protocol 7: Comparing tissue-specific expression using the Tissue Distribution tool.

Synergy between Human Peptide LL-37 and Polymyxin B against Planktonic and Biofilm Cells of Escherichia coli and Pseudomonas aeruginosa.

The rise in antimicrobial resistant bacteria is limiting the number of effective treatments for bacterial infections. Escherichia coli and Pseudomonas aeruginosa are two of the pathogens with the highest prevalence of resistance, and with the greatest need for new antimicrobial agents. Combinations of antimicrobial peptides (AMPs) and antibiotics that display synergistic effects have been shown to be an effective strategy in the development of novel therapeutic agents. In this study, we investigated the synergy between the AMP LL-37 and various classes of antibiotics against E. coli and P. aeruginosa strains. Of the six antibiotics tested (ampicillin, tetracycline, ciprofloxacin, gentamicin, aztreonam, and polymyxin B (PMB)), LL-37 displayed the strongest synergy against E. coli MG1655 and P. aeruginosa PAO1 laboratory strains when combined with PMB. Given the strong synergy, the PMB + LL-37 combination was chosen for further examination where it demonstrated synergy against multidrug-resistant and clinical E. coli isolates. Synergy of PMB + LL-37 towards clinical isolates of P. aeruginosa varied and showed synergistic, additive, or indifferent effects. The PMB + LL-37 combination treatment showed significant prevention of biofilm formation as well as eradication of pre-grown E. coli and P. aeruginosa biofilms. Using the Galleria mellonella wax worm model, we showed that the PMB + LL-37 combination treatment retained its antibacterial capacities in vivo. Flow analyses were performed to characterize the mode of action. The results of the present study provide proof of principle for the synergistic response between LL-37 and PMB and give novel insights into a promising new antimicrobial combination against gram-negative planktonic and biofilm cells.

Discovery of Natural Small Molecules Promoting Collagen Secretion by High-Throughput Screening in Caenorhabditis elegans

Advancing approaches for drug screening are in great demand to explore natural small molecules that may play important roles in collagen biogenesis, secretion, and assembly, which may find novel lead compounds for treating collagen-related diseases or preventing skin aging. In this study, we generated a single copy insertion transgenic Pcol-19- COL-12::GFP Caenorhabditis elegans (C. elegans) strain to label epidermis collagen XII (COL-12), a cuticle structure component, and established an efficient high-content screening techniques to discover bioactive natural products in this worm strain through quantification of fluorescence imaging. We performed a preliminary screening of 614 compounds from the laboratory's library of natural small molecule compounds on the COL-12 labeling worm model, which was tested once at a single concentration of 100 µM to screen for compounds that promoted COL-12 protein amount. Besides col-12, the transcriptional levels of worm-associated collagen coding genes col-19 and sqt-3 were also examined, and none of the compounds affected their transcriptional levels. Meanwhile, the protein levels of COL-12 were significantly upregulated after treating with Danshensu, Lawsone, and Sanguinarine. The effects of these drugs on COL-12 overexpressing worms occur mainly after collagen transcription. Through various validation methods, Danshensu, Lawsone, and Sanguinarine were more effective in promoting the synthesis or secretion of COL-12.

A Caenorhabditis elegans model of autosomal dominant adult-onset neuronal ceroid lipofuscinosis identifies ethosuximide as a potential therapeutic.

Autosomal dominant adult-onset neuronal ceroid lipofuscinosis (ANCL) is a rare neurodegenerative disorder characterized by progressive dementia and premature death. Four ANCL-causing mutations have been identified, all mapping to the DNAJC5 gene that encodes cysteine string protein α (CSPα). Here, using Caenorhabditis elegans, we describe an animal model of ANCL in which disease-causing mutations are introduced into their endogenous chromosomal locus, thereby mirroring the human genetic disorder. This was achieved through CRISPR/Cas9-mediated gene editing of dnj-14, the C. elegans ortholog of DNAJC5. The resultant homozygous ANCL mutant worms exhibited reduced lifespans and severely impaired chemotaxis, similar to isogenic dnj-14 null mutants. Importantly, these phenotypes were also seen in balanced heterozygotes carrying one wild-type and one ANCL mutant dnj-14 allele, mimicking the heterozygosity of ANCL patients. We observed a more severe chemotaxis phenotype in heterozygous ANCL mutant worms compared with haploinsufficient worms lacking one copy of CSP, consistent with a dominant-negative mechanism of action. Additionally, we provide evidence of CSP haploinsufficiency in longevity, as heterozygous null mutants exhibited significantly shorter lifespan than wild-type controls. The chemotaxis phenotype of dnj-14 null mutants was fully rescued by transgenic human CSPα, confirming the translational relevance of the worm model. Finally, a focused compound screen revealed that the anti-epileptic drug ethosuximide could restore chemotaxis in dnj-14 ANCL mutants to wild-type levels. This suggests that ethosuximide may have therapeutic potential for ANCL and demonstrates the utility of this C. elegans model for future larger-scale drug screening.

Study on the meshing evolving mechanism of a novel self-evolution hourglass worm drive

To satisfy the increasing unique characteristics of high precision and heavy-load performance in industrial equipment, a novel self-evolution hourglass worm drive is proposed in this paper. It is consisted of an involute helical beveloid (IHB) gear and an oblique planar enveloping (OPE) hourglass worm, and this worm drive gradually evolves from a local conjugate hourglass worm drive with point contact in the initial meshing state, and a middle meshing state (MES) hourglass worm drive with short-line contact with continuous operation and wear, as well as the finally evolves into a toroidal involute (TI) hourglass worm drive with line contact. According to the differential geometry theory and the spatial meshing principle, the mathematical models of this novel self-evolution hourglass worm drive are established in each evolution stage, the theory of backlash-adjustable is confirmed with introducing a pair of transition tooth surfaces, and the meshing contact area evolution mechanism was defined and elaborated. In addition, the meshing performance evolution of the contact area and the bearing capacity are simulated by numerical analysis including tooth contact analysis and finite element analysis. The analysis results show that with the continuous evolution, the contact area keeps increasing, and the bearing capacity also keeps improving. This study will provide a theoretical basis for the industrial application of this novel hourglass worm drive.

In vivo, in vitro and molecular docking studies reveal the anti-virulence property of hispidulin against Pseudomonas aeruginosa through the modulation of quorum sensing

Pseudomonas aeruginosa is an audacious infectious agent involved in multiple persistent and incurable diseases in hosts through quorum sensing mediated pathways. Thus, compounds targeting quorum sensing (QS) can reduce the pathogenesis and virulence. The present study attempts to elucidate the QS inhibition properties of hispidulin against P. aeruginosa PAO1. Hispidulin (HPD) at its sub-inhibitory concentration (75 μg/ml) decreased violacein and pyocyanin pigment production of reporter bacteria and test bacteria to 81.92 ± 1.90 and 71.69 ± 3.46%, respectively. HPD supressed the virulence and biofilm development as similar to the positive control, baicalein. The pathogenesis of P. aeruginosa was effectively reduced in the infected worm model. The infected C. elegans showed 80.43% survival on the 6th day in presence of sub-MIC of HPD. In addition, HPD reduced the transcription of genes regulated by Las and Rhl networks including the receptor proteins and autoinducer producing genes which validated the anti-QS potential of the flavonoid. Computational studies revealed competitive binding of HPD with LasR protein and a weak interaction with RhlR. The results suggested the ability of HPD to block QS regulatory networks of P. aeruginosa. The potential lead obtained through this study can be utilized in the near future to design and develop anti-pathogenic agents to treat pseudomonal infections.

From bugs to bedside: functional annotation of human genetic variation for neurological disorders using invertebrate models.

The exponential accumulation of DNA sequencing data has opened new avenues for discovering the causative roles of single-nucleotide polymorphisms (SNPs) in neurological diseases. The opportunities emerging from this are staggering, yet only as good as our abilities to glean insights from this surplus of information. Whereas computational biology continues to improve with respect to predictions and molecular modeling, the differences between in silico and in vivo analysis remain substantial. Invertebrate in vivo model systems represent technically advanced, experimentally mature, high-throughput, efficient and cost-effective resources for investigating a disease. With a decades-long track record of enabling investigators to discern function from DNA, fly (Drosophila) and worm (Caenorhabditis elegans) models have never been better poised to serve as living engines of discovery. Both of these animals have already proven useful in the classification of genetic variants as either pathogenic or benign across a range of neurodevelopmental and neurodegenerative disorders-including autism spectrum disorders, ciliopathies, amyotrophic lateral sclerosis, Alzheimer's and Parkinson's disease. Pathogenic SNPs typically display distinctive phenotypes in functional assays when compared with null alleles and frequently lead to protein products with gain-of-function or partial loss-of-function properties that contribute to neurological disease pathogenesis. The utility of invertebrates is logically limited by overt differences in anatomical and physiological characteristics, and also the evolutionary distance in genome structure. Nevertheless, functional annotation of disease-SNPs using invertebrate models can expedite the process of assigning cellular and organismal consequences to mutations, ascertain insights into mechanisms of action, and accelerate therapeutic target discovery and drug development for neurological conditions.

Experimental investigation of efficiency of worm gears and modeling of power loss through artificial neural networks

In this study, an experimental system that can operate at different speeds and loading rates was developed for the efficiency calculations of worm gears (WGs), and measurements were made accordingly. A comprehensive efficiency analysis has been made for WGs based on power loss calculations under different operating conditions. The efficiencies obtained from the healthy gearbox were also compared with three different gearboxes with different failures (pitting, wear and breakage). The negative effect of the faults on the efficiency that may occur in the gearbox has been investigated comparatively. A widely used type of machine learning algorithms, called artificial neural network (ANN), is applied for data-driven modeling of the power loss in WG under different operating conditions. The input and output power of the gearbox are utilized to design an ANN-based model for the power loss.