Research on vibration characteristics of gear-coupled multi-shaft rotor-bearing systems under the excitation of unbalance

To find out the effect of eccentricity of a gear wheel on inherent characteristics of a gear-rotor system, this paper establishes a pair of general transverse-rotational-axial-swinging multi degrees of freedom coupling helical gear meshing dynamic model based on the finite element method (FEM). Considering the influence of the azimuth, the meshing angle, the helix angle and the rotation direction of driving shaft on mesh stiffness matrix, it analyzes the effect of mesh stiffness and mesh damping on the inherent characteristics and the transient response of the system. It obtains the displacement response curve and the dynamic meshing force curve of all nodes responding to the incentives of static transmission error and unbalance while considering mesh damping. It concludes that the effects of gear coupling and eccentricity of gear wheel should be taken into account in a multi-parallel-shaft gear meshing rotor system

A Comprehensive Molecular Interaction Map for Rheumatoid Arthritis

Computational biology contributes to a variety of areas related to life sciences and, due to the growing impact of translational medicine - the scientific approach to medicine in tight relation with basic science -, it is becoming an important player in clinical-related areas. In this study, we use computation methods in order to improve our understanding of the complex interactions that occur between molecules related to Rheumatoid Arthritis (RA).Due to the complexity of the disease and the numerous molecular players involved, we devised a method to construct a systemic network of interactions of the processes ongoing in patients affected by RA. The network is based on high-throughput data, refined semi-automatically with carefully curated literature-based information. This global network has then been topologically analysed, as a whole and tissue-specifically, in order to translate the experimental molecular connections into topological motifs meaningful in the identification of tissue-specific markers and targets in the diagnosis, and possibly in the therapy, of RA.’

Frontotemporal Dementia Nonsense Mutation of Progranulin Rescued by Aminoglycosides

Frontotemporal dementia (FTD) is an early onset dementia and is characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5-26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its function under physiological and pathological conditions remains to be defined. Many FTD-causing nonsense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy. Aminoglycosides are a class of antibiotics that possess a less known function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein. The aminoglycoside-induced readthrough strategy has been utilized to treat multiple human diseases caused by PTCs. In this study, we tested the only clinically approved readthrough small molecule PTC124 and eleven aminoglycosides in a cell culture system on four PTCs responsible for FTD or a related neurodegenerative disease amyotrophic lateral sclerosis. We found that the aminoglycosides G418 and gentamicin B1 rescued the expression of the progranulin R493X mutation. G418 was more effective than gentamicin B1 (~50% rescue vs \u3c 10%), and the effect was dose and time-dependent. The proganulin readthrough protein displayed similar subcellular localization as the wild-type proganulin protein. These data provide an exciting proof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue for familial FTD caused by proganulin PTC mutations

ALS Mutations of FUS Suppress Protein Translation and Disrupt the Regulation of Nonsense-Mediated Decay

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid–liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed a protocol to isolate the dynamic mutant FUS-positive cytoplasmic granules. Proteomic identification of the protein composition and subsequent pathway analysis led us to hypothesize that mutant FUS can interfere with protein translation. We demonstrated that the ALS mutations in FUS indeed suppressed protein translation in N2a cells expressing mutant FUS and fibroblast cells derived from FUS ALS cases. In addition, the nonsense-mediated decay (NMD) pathway, which is closely related to protein translation, was altered by mutant FUS. Specifically, NMD-promoting factors UPF1 and UPF3b increased, whereas a negative NMD regulator, UPF3a, decreased, leading to the disruption of NMD autoregulation and the hyperactivation of NMD. Alterations in NMD factors and elevated activity were also observed in the fibroblast cells of FUS ALS cases. We conclude that mutant FUS suppresses protein biosynthesis and disrupts NMD regulation, both of which likely contribute to motor neuron death

Peptide-fluorescent bacteria complex as luminescent reagents for cancer diagnosis

Currently in clinic, people use hematoxylin and eosin stain (H&E stain) and immunohistochemistry methods to identify the generation and genre of cancers for human pathological samples. Since these methods are inaccurate and time consuming, developing a rapid and accurate method to detect cancer is urgently demanded. In our study, binding peptides for lung cancer cell line A549 were identified using bacteria surface display method. With those binding peptides for A549 cells on the surface, the fluorescent bacteria (Escherichia coli with stably expressed green fluorescent protein) were served as specific detecting reagents for the diagnosis of cancers. The binding activity of peptide-fluorescent bacteria complex was confirmed by detached cancer cells, attached cancer cells and mice tumor xenograft samples. A unique fixation method was developed for peptide-bacteria complex in order to make this complex more feasible for the clinic use. This peptide-fluorescent bacteria complex has great potential to become a new diagnostic tool for clinical application

Blood nesfatin-1 levels in patients with polycystic ovary syndrome: a systematic review and meta-analysis

BackgroundPrevious studies have investigated the relationship between nesfatin-1 level and polycystic ovary syndrome (PCOS). However, these studies have produced conflicting results. Thus, in this meta-analysis, we aimed to clarify the association between blood nesfatin-1 levels and PCOS, and the ability of nesfatin-1 as a biomarker in PCOS.MethodsMeta-analysis was performed using STATA 12.0 software. We computed standard mean difference (SMD) and 95% confidence interval (CI) regarding the comparison of blood nesfatin-1 in patients with PCOS and controls.ResultsThe present meta-analysis showed no significant difference in blood nesfatin-1 level between patients with PCOS and controls with a random effects model (SMD = 0.03; 95%CI: -0.71, 0.77; I2 = 97.1%, p value for Q test < 0.001). Subgroup analysis for different ethnicities reported no significant difference in blood nesfatin-1 level between patients with PCOS and controls in both Caucasian and Asian populations. Subgroup analysis for different sample types reported no significant difference in serum nesfatin-1 level between patients with PCOS and controls. Subgroup studies reported no significant difference in blood nesfatin-1 level between PCOS and controls in both obese and non-obese populations.ConclusionIn conclusion, there is no significant relationship between blood nesfatin-1 levels and PCOS

I2^2-SDF: Intrinsic Indoor Scene Reconstruction and Editing via Raytracing in Neural SDFs

In this work, we present I$^2$-SDF, a new method for intrinsic indoor scene reconstruction and editing using differentiable Monte Carlo raytracing on neural signed distance fields (SDFs). Our holistic neural SDF-based framework jointly recovers the underlying shapes, incident radiance and materials from multi-view images. We introduce a novel bubble loss for fine-grained small objects and error-guided adaptive sampling scheme to largely improve the reconstruction quality on large-scale indoor scenes. Further, we propose to decompose the neural radiance field into spatially-varying material of the scene as a neural field through surface-based, differentiable Monte Carlo raytracing and emitter semantic segmentations, which enables physically based and photorealistic scene relighting and editing applications. Through a number of qualitative and quantitative experiments, we demonstrate the superior quality of our method on indoor scene reconstruction, novel view synthesis, and scene editing compared to state-of-the-art baselines.Comment: Accepted by CVPR 202

Clinical and Experimental Studies of a Novel P525R FUS Mutation in Amyotrophic Lateral Sclerosis

Objective: To describe the clinical features of a novel fused in sarcoma (FUS) mutation in a young adult female amyotrophic lateral sclerosis (ALS) patient with rapid progression of weakness and to experimentally validate the consequences of the P525R mutation in cellular neuronal models. Methods: We conducted sequencing of genomic DNA from the index patient and her family members. Immunocytochemistry was performed in various cellular models to determine whether the newly identified P525R mutant FUS protein accumulated in cytoplasmic inclusions. Clinical features of the index patient were compared with 19 other patients with ALS carrying the P525L mutation in the same amino acid position. Results: A novel mutation c.1574C\u3eG (p.525P\u3eR) in the in the FUS gene was identified in the index patient. The clinical symptoms are similar to those in familial ALS patients with the P525L mutation at the same position. The P525R mutant FUS protein showed cytoplasmic localization and formed large stress granule–like cytoplasmic inclusions in multiple cellular models. Conclusions: The clinical features of the patient and the cytoplasmic inclusions of the P525R mutant FUS protein strengthen the notion that mutations at position 525 of the FUS protein result in a coherent phenotype characterized by juvenile or young adult onset, rapid progression, variable positive family history, and female preponderance