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Abstract This study introduces a method to predict the remaining useful life (RUL) of plain bearings operating under stationary, wear-critical conditions. In this method, the transient wear data of a coupled elastohydrodynamic lubrication (mixed-EHL) and wear simulation approach is used to parametrize a statistical, linear degradation model. The method incorporates Bayesian inference to update the linear degradation model throughout the runtime and thereby consider the transient, system-dependent wear progression within the RUL prediction. A case study is used to show the suitability of the proposed method. The results show that the method can be applied to three distinct types of post-wearing-in behavior: wearing-in with subsequent hydrodynamic, stationary wear, and progressive wear operation. While hydrodynamic operation leads to an infinite lifetime, the method is successfully applied to predict RUL in cases with stationary and progressive wear.

Introduction: Polymorphisms in genes responsible for the metabolism and transport of tacrolimus have been demonstrated to influence clinical outcomes for patients following allogeneic hematologic stem cell transplant (allo-HSCT). However, the clinical impact of germline polymorphisms specifically for oral formulations of tacrolimus is not fully described.Methods: To investigate the clinical impact of genetic polymorphisms in CYP3A4, CYP3A5, and ABCB1 on oral tacrolimus pharmacokinetics and clinical outcomes, we prospectively enrolled 103 adult patients receiving oral tacrolimus for the prevention of graft-versus-host disease (GVHD) following allo-HSCT. Patients were followed in the inpatient and outpatient phase of care for the first 100 days of tacrolimus therapy. Patients were genotyped for CYP3A5 *3 (rs776746), CYP3A4 *1B (rs2740574), ABCB1 exon 12 (rs1128503), ABCB1 exon 21 (rs2032582), ABCB1 exon 26 (rs1045642).Results: Expression of CYP3A5 *1 was highly correlated with tacrolimus pharmacokinetics in the inpatient phase of care (p < 0.001) and throughout the entirety of the study period (p < 0.001). Additionally, Expression of CYP3A5 *1 was associated with decreased risk of developing AKI as an inpatient (p = 0.06). Variants in ABCB1 were not associated with tacrolimus pharmacokinetics in this study. We were unable to discern an independent effect of CYP3A4 *1B or *22 in this population.Conclusion: Expression of CYP3A5 *1 is highly influential on the pharmacokinetics and clinical outcomes for patients receiving oral tacrolimus as GVHD prophylaxis following allo-HSCT.

Background: To test efficacy, HIV cure-related trials often require a period of intensively monitored interruption of antiretroviral therapy (ART) (analytical treatment interruption or ATI). As individuals who started ART during primary HIV-1 infection (PHI) are often recruited, we have asked people already enrolled into an observational PHI study about their willingness and concerns around participating in cure-related studies involving ATIs. Methods: People who were diagnosed with PHI and started ART, attending two London HIV clinics, provided informed consent to complete a digital survey in clinic between 21/07/21 to October 31, 2023. Questions comprised sociodemographics, motivations, concerns and practical considerations influencing willingness to participate in studies involving ATIs. Hierarchical clustering of responses was performed using the ‘pheatmap’ R statistical package and ranked from most to least concerned. Responses were cross-referenced with enrolment into an ATI study which recruited from this cohort. Results: Of 352 eligible participants, 75 completed the survey. The majority were white, cisgender men who have sex with men, 34/75 (45 %) were born outside the UK. 29 (39 %) expressed interest in joining ATI studies. Participants who were interested or unsure in joining ATI studies were primarily motivated (53/65, 82 % very or moderately interested) by an altruistic desire to help scientific research. Across all participants, onward HIV transmission was the predominant concern (67/75, 89 % very or moderately concerned), and similar levels of concerns reported if the HIV-1 viral load threshold to restarting ART was increased from 500 to 50 000 copies/mL. Most participants preferred weekly (23/65, 35 %) or fortnightly (11/65, 17 %) viral load monitoring during an ATI. Before taking part in a study involving an ATI, participants stated they would prefer to discuss this with their HIV doctor (55/65, 85 %). Conclusion: In this small survey, 39 % of respondents expressed interest in joining studies involving ATIs, primarily for altruistic reasons. Participants were more interested in joining a potential ATI study if a novel intervention was included than simply an ATI alone. The main concern expressed was risk of viral transmission. To inform practical and study design considerations for future ATI studies, unrestricted access for mitigation of transmission risk should be included, and regular, frequent viral load monitoring is preferred.

Among breast cancer subtypes, triple-negative breast cancer stands out as the most aggressive, with patients facing a 40% mortality rate within the initial five years. The limited treatment options and unfavourable prognosis for triple-negative patients necessitate the development of novel therapeutic strategies. Photodynamic therapy (PDT) is an alternative treatment that can effectively target triple-negative neoplastic cells such as MDA-MB-231. In this in vitro study, we conducted a comparative analysis of the PDT killing rate of unbound Rose Bengal (RB) in solution versus RB-encapsulated chitosan nanoparticles to determine the most effective approach for inducing cytotoxicity at low laser powers (90 mW, 50 mW, 25 mW and 10 mW) and RB concentrations (50 µg/mL, 25 µg/mL, 10 µg/mL and 5 µg/mL). Intracellular singlet oxygen production and cell uptake were also determined for both treatment modalities. Dark toxicity was also assessed for normal breast cells. Despite the low laser power and concentration of nanoparticles (10 mW and 5 µg/mL), MDA-MB-231 cells experienced a substantial reduction in viability (8 ± 1%) compared to those treated with RB solution (38 ± 10%). RB nanoparticles demonstrated higher singlet oxygen production and greater uptake by cancer cells than RB solutions. Moreover, RB nanoparticles display strong cytocompatibility with normal breast cells (MCF-10A). The low activation threshold may be a crucial advantage for specifically targeting malignant cells in deep tissues.

Yan Wei,1,&ast; Jin Zhao,1,&ast; Jian Ming,1 Xuewu Zhang,2 Yingyao Chen1 1National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 2Department of Rheumatology, Peking University People’s Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuewu Zhang, Department of Rheumatology, Peking University People’s Hospital, Beijing, People’s Republic of China, Tel +8613681573403, Fax +86-010-88366323, Email xuewulore@163.com Yingyao Chen, National Health Commission Key Laboratory of Health Technology Assessment, School of Public Health, Fudan University, Shanghai, 200032, People’s Republic of China, Tel +86-21-33565183, Fax +86-21-64169552, Email yychen@shmu.edu.cnObjective: Rheumatoid arthritis (RA) is increasingly treated with biologics, which is commonly administered by injection devices. The aim of this study is to evaluate patients’ preferences for self-injection devices in RA, and to elicit their willingness to pay (WTP) for injector devices in China.Methods: RA patients were recruited from Beijing, Shanghai, Guangzhou, Chengdu, Wuhan and Xi’an in China. A discrete choice experiment (DCE) was employed to elicit patient preferences. Patients were presented with 15 choice sets that consisted of seven attributes, which were developed based on literature review and further validated by physicians. The seven attributes were as follows: operation steps, injection pain, feedback indication, needle visibility, needle protection, size and out-of-pocket costs. A mixed logit model was used to analyze the relative importance of seven attributes and to calculate the WTP for a changed attribute level.Results: Analyses included 114 adults with RA (mean age of 44.6 years old). When choosing the injection device, all attributes had significant influence. Among nonmonetary attributes, very slight injection pain was the most preferred for patients, followed by auto-injection method, thicker size, hidden needle, with needle protection and multiple feedback indication. Patients had a negative preference for increasing out-of-pocket costs. Patients were willing to pay CNY 45.26 for improving slight injection pain to very slight injection pain, CNY 13.26 for the auto-injection method, CNY 12.22 for the thicker size, CNY 10.06 for the hidden needle, CNY 9.82 for needle protection, and CNY 9.70 for multiple feedback indicators.Conclusion: The results suggested that injection pain was the most important attribute for RA patients. Meanwhile, all other enhanced attributes of self-injection devices also significantly influence patients’ selection on injection devices. Findings suggested that there is significant potential value in developing self-injection devices that could further help improve treatment adherence and promote patient-centered care in autoimmune diseases.Keywords: self-injection devices, rheumatoid arthritis, patient preferences, discrete choice experiment

Multiple Myeloma (MM) is an incurable plasma cell malignancy often treated by autologous stem cell transplant (ASCT). Clinical response to ASCT has been associated with DNA repair efficiency. Here we interrogated the role of the base excision DNA repair (BER) pathway in MM response to ASCT. Across 450 clinical samples and six disease stages, expression levels of genes in the BER pathway were found to be highly upregulated during the development of MM. In a separate cohort of 559 patients with MM treated with ASCT, expression of BER pathway members MPG and PARP3 was positively associated with overall survival (OS) while expression of PARP1, POLD1, and POLD2 was negatively associated with OS. In a validation cohort of 356 patients with MM treated with ASCT, PARP1 and POLD2 findings were replicated. In patients with MM who never received ASCT (n=319), PARP1 and POLD2 were not associated with OS, suggesting that the prognostic effect of these genes may be treatment-dependent. In preclinical models of MM, synergy was observed in anti-tumor activity when poly (ADPribose) polymerase (PARP) inhibitors (olaparib, talazoparib) were used in combination with melphalan. The negative prognosis associated with PARP1 and POLD2 expression along with the apparent melphalan-sensitizing effect of PARP inhibition may suggest this pathway as a potential biomarker in patients with MM in the setting of ASCT. Further understanding of the role of the BER pathway in MM is vital to improve therapeutic strategies related to ASCT.

Cancer, a prominent cause of death, presents treatment challenges, including high dosage requirements, drug resistance, poor tumour penetration and systemic toxicity in traditional chemotherapy. Photodynamic therapy, using photosensitizers like rose bengal (RB) with a green laser, shows promise against breast cancer cells in vitro. However, the hydrophilic RB struggles to efficiently penetrate the tumour site due to the unique clinical microenvironment, aggregating around rather than entering cancer cells. In this study, we have synthesized and characterized RB-encapsulated chitosan nanoparticles with a peak particle size of ~200 nm. These nanoparticles are readily internalized by cells and, in combination with a green laser (λ = 532 nm) killed 94–98% of cultured human breast cancer cells (MCF-7) and prostate cancer cells (PC3) at a low dosage (25 μg/mL RB-nanoparticles, fluence ~126 J/cm2, and irradiance ~0.21 W/cm2). Furthermore, these nanoparticles are not toxic to cultured human normal breast cells (MCF10A), which opens an avenue for translational applications.

Fowl adenoviruses (FAdVs) are distributed worldwide in poultry and incriminated as the etiological agents for several health problems in fowls, and are capable of crossing species barriers between domestic and wild fowls. An FAdV strain was, for the first time, isolated from black-necked crane in this study, and was designated as serotype 4 Fowl aviadenovirus C (abbreviated as BNC2021) according to the phylogenetic analysis of its DNA polymerase and hexon gene. The viral genomic sequence analysis demonstrated that the isolate possessed the ORF deletions that are present in FAdV4 strains circulating in poultry fowls in China and the amino acid mutations associated with viral pathogenicity in the hexon and fiber 2 proteins. A viral challenge experiment with mallard ducks demonstrated systemic viral infection and horizontal transmission. BNC2021 induced the typical clinical signs of hepatitis–hydropericardium syndrome (HHS) with swelling and inflammation in multiple organs and showed significant viral replication in all eight organs tested in the virus-inoculated ducks and their contactees at 6 dpi. The findings highlight the importance of surveillance of FAdVs in wild birds.

Adeno-associated virus (AAV) capsid libraries have generated improved transgene delivery vectors. We designed an AAV library construct, iTransduce, that combines a peptide library on the AAV9 capsid with a Cre cassette to enable sensitive detection of transgene expression. After only two selection rounds of the library delivered intravenously in transgenic mice carrying a Cre-inducible fluorescent protein, we flow sorted fluorescent cells from brain, and DNA sequencing revealed two dominant capsids. One of the capsids, termed AAV-F, mediated transgene expression in the brain cortex more than 65-fold (astrocytes) and 171-fold (neurons) higher than the parental AAV9. High transduction efficiency was sex-independent and sustained in two mouse strains (C57BL/6 and BALB/c), making it a highly useful capsid for CNS transduction of mice. Future work in large animal models will test the translation potential of AAV-F. Keywords: adeno-associated virus vector, AAV vector, gene therapy, gene delivery, central nervous system, transduction efficiency, AAV capsid library

The seasonal migration of wild aquatic birds plays a critical role in the maintenance, transmission, and incursion of the avian influenza virus (AIV). AIV surveillance was performed during 2020–2021 in two national nature reserves with abundant wild bird resources in Yunnan, China. Four H5N8 AIVs isolates from the common crane were identified by next-generation sequencing. Phylogenetic analysis demonstrated that all eight gene segments of these H5N8 AIVs belonged to clade 2.3.4.4b high-pathogenic AIV (HPAIV) and shared high nucleotide sequence similarity with the strains isolated in Hubei, China, and Siberia, Russia, in 2020–2021. The H5N8 HPAIVs from common cranes were characterized by both human and avian dual-receptor specificity in the hemagglutinin (HA) protein. Moreover, possessing the substitutions contributes to overcoming transmission barriers of mammalian hosts in polymerase basic 2 (PB2), polymerase basic protein 1 (PB1), and polymerase acid (PA), and exhibiting the long stalk in the neck region of the neuraminidase (NA) protein contributes to adaptation in wild birds. Monitoring AIVs in migratory birds, at stopover sites and in their primary habitats, i.e., breeding or wintering grounds, could provide insight into potential zoonosis caused by AIVs.

This paper presents methods for the 2019 PHM Conference Data Challenge developed by the team named "Angler". This Challenge aims to estimate the fatigue crack length of a type of aluminum structure using ultrasonic signals at the current load cycle and to predict the crack length at multiple future load cycles (multiple-step-ahead prediction) as accurately as possible. For estimating crack length, four crack-sensitive features are extracted from ultrasonic signals, namely, the first peak value, root mean square value, logarithm of kurtosis, and correlation coefficient. An ensemble linear regression model is presented to map these features and their second-order interactions with the crack length. The Best Subset Selection method is employed to select the optimal features. For predicting crack length, variations of the Paris’ law are derived to describe the relationships between the crack length and the number of load cycles. The material parameters and stress range of Paris’ law are learned using the Genetic Algorithm. These parameters will be updated based on the previous-step predicted crack length. After that, the crack length corresponding to a future load cycle number for either the constant amplitude load case or variable amplitude load case is predicted. The presented methods achieved a score of 16.14 based on the score-calculation rule provided by the Data Challenge committees, and was ranked third best among all participating teams.

Bifan Zhu,1 Yanfang Wang,2 Jian Ming,3 Wen Chen,4 Luying Zhang4 1Shanghai Health Development Research Center, Shanghai Medical Information Center, Shanghai, China; 2The First Affiliated Hospital of Wannan Medical College, Wuhu, China; 3IQVIA, Shanghai, China; 4School of Public Health, Fudan University, Shanghai, China Abstract: Chronic obstructive pulmonary disease (COPD) is one of the main contributors to the global burden of disease. The aim of this systematic review was to quantify the disease burden of COPD in China and to determine the risk factors of the disease. The number of studies included in the review was 47 with an average quality assessment score of 7.70 out of 10. Reported COPD prevalence varied between 1.20% and 8.87% in different provinces/cities across China. The prevalence rate of COPD was higher among men (7.76%) than women (4.07%). The disease was more prevalent in rural areas (7.62%) than in urban areas (6.09%). The diagnostic rate of COPD patients in China varied from 23.61% to 30.00%. The percentage of COPD patients receiving outpatient treatment was around 50%, while the admission rate ranged between 8.78% and 35.60%. Tobacco exposure and biomass fuel/solid fuel usage were documented as two important risk factors of COPD. COPD ranked among the top three leading causes of death in China. The direct medical cost of COPD ranged from 72 to 3,565 USD per capita per year, accounting for 33.33% to 118.09% of local average annual income. The most commonly used scales for the assessment of quality of life (QoL) included Saint George Respiratory Questionnaire, Airways Questionnaire 20, SF-36, and their revised versions. The status of QoL was worse among COPD patients than in non-COPD patients, and COPD patients were at higher risks of depression. The COPD burden in China was high in terms of economic burden and QoL. In view of the high smoking rate and considerable concerns related to air pollution and smog in China, countermeasures need to be taken to improve disease prevention and management to reduce disease burdens raised by COPD. Keywords: COPD, burden of disease, systematic review

Xinghuai Sun,1,2 Mingkai Lin,3 Xuanchu Duan,4 Chun Zhang,5 Jian Ming6 1Eye, Ear, Nose and Throat Hospital, Shanghai Medical College, Fudan University, Shanghai, 2Key Laboratory of Myopia, Ministry of Health (Fudan University), and Shanghai Key Laboratory of Visual Impairment and Restoration (Fudan University), Shanghai, 3Zhongshan Ophthalmic Center, Guangzhou, 4The Second Xiangya Hospital of Central South University, Changsha, 5Peking University Third Hospital, Beijing, 6Allergan plc, Shanghai, People’s Republic of China Background: Poor adherence to treatment is a problem in glaucoma, and patient dissatisfaction with topical glaucoma medication is a barrier to adherence. The objective of this study was to evaluate glaucoma patients’ satisfaction with fixed-combination bimatoprost/timolol ophthalmic solution (BTFC). Methods: This observational, multicenter study was conducted in China in adults with glaucoma treated with BTFC for 1–3 months. Five hundred patients answered a questionnaire concerning their demographic characteristics, history of glaucoma and topical glaucoma treatment, and use of BTFC. The primary endpoint was patient satisfaction with BTFC assessed on a 10-point scale (1= very dissatisfied, 10= very satisfied).Results: Patients received BTFC alone (65%) or with other treatments (35%), most commonly a carbonic anhydrase inhibitor. Most patients (87%) used BTFC as a replacement for other medication, usually a β-blocker or prostaglandin analog; 13% received BTFC as add-on treatment. Key reasons for initiating BTFC therapy were poor efficacy of previous treatment (72% of patients) and side effects of previous treatment (32% of patients). Most patients agreed or very much agreed that BTFC provided better control of intraocular pressure (85% of patients), had a simpler administration (87% of patients), and was associated with better tolerance and comfort (82% of patients) compared with their previous treatment. Mean satisfaction scores were significantly higher for BTFC than for previous treatments among all patients (7.8 versus 6.0; P

Effective signal processing methods are essential for machinery fault diagnosis. Most conventional signal processing methods lack adaptability, thus being unable to well extract the embedded meaningful information. Adaptive mode decomposition methods have excellent adaptability and high flexibility in describing arbitrary complicated signals, and are free from the limitations imposed by conventional basis expansion, thus being able to adapt to the signal characteristics, extract rich characteristic information, and therefore reveal the underlying physical nature. This paper presents a systematic and up-to-date review on adaptive mode decomposition in two major topics, i.e., mono-component decomposition algorithms (such as empirical mode composition, local mean decomposition, intrinsic time-scale decomposition, local characteristic scale decomposition, Hilbert vibration decomposition, empirical wavelet transform, variational mode decomposition, nonlinear mode decomposition, and adaptive local iterative filtering) and instantaneous frequency estimation approaches (including Hilbert-transform-based analytic signal, direct quadrature, and normalized Hilbert transform based on empirical AM-FM decomposition, as well as generalized zero-crossing and energy separation) reported in more than 80 representative articles published since 1998. Their fundamental principles, advantages and disadvantages, and applications to signal analysis in machinery fault diagnosis, are examined. Examples are provided to illustrate their performance.

Batten disease, or juvenile NCL, is a fatal neurodegenerative disorder that occurs due to mutations in the CLN3 gene. Because the function of CLN3 remains unclear, experimental therapies for JNCL have largely concentrated upon the targeting of downstream pathomechanisms. Neuron loss is preceded by localized glial activation, and in this proof-of-concept study we have investigated whether targeting this innate immune response with ibuprofen in combination with the neuroprotective agent lamotrigine improves the previously documented beneficial effects of immunosuppressants alone. Drugs were administered daily to symptomatic Cln3−/− mice over a 3 month period, starting at 6 months of age, and their impact was assessed using both behavioral and neuropathological outcome measures. During the treatment period, the combination of ibuprofen and lamotrigine significantly improved the performance of Cln3−/− mice on the vertical pole test, slowing the disease-associated decline, but had less of an impact upon their rotarod performance. There were also moderate and regionally dependent effects upon astrocyte activation that were most pronounced for ibuprofen alone, but there was no overt effect upon microglial activation. Administering such treatments for longer periods will enable testing for any impact upon the neuron loss that occurs later in disease progression. Given the partial efficacy of these treatments, it will be important to test further drugs of this type in order to find more effective combinations.

Abstract Background Alport syndrome (AS) is a hereditary disease caused by mutations in COL4A3‐5 genes. Recently, comprehensive genetic analysis has become the first‐line diagnostic tool for AS. However, no reports comparing mutation identification rates between conventional sequencing and comprehensive screening have been published. Methods In this study, 441 patients clinically suspected of having AS were divided into two groups and compared. The initial mutational analysis method involved targeted exome sequencing using next‐generation sequencing (NGS) (n = 147, NGS group) or Sanger sequencing for COL4A3/COL4A4/COL4A5 (n = 294, Sanger group). Results In the NGS group, 126 patients (86%) were diagnosed with AS by NGS, while two had pathogenic mutations in other genes, NPHS1 and EYA1. Further, 239 patients (81%) were diagnosed with AS by initial analysis in the Sanger group. Thirteen patients who were negative for mutation detection in the Sanger group were analyzed by NGS; three were diagnosed with AS. Two had mutations in CLCN5 or LAMB2. The final variant detection rate was 90%. Discussion Our results reveal that Sanger sequencing and targeted exome sequencing have high diagnostic ability. NGS also has the advantage of detecting other inherited kidney diseases and pathogenic mutations missed by Sanger sequencing.

Planetary gearbox systems are critical mechanical components in heavy machinery such as wind turbines. They may suffer from various failure modes, due to the harsh working environment. Dynamic modeling is a useful method to support early fault detection for enhancing reliability and reducing maintenance costs. However, reported studies have not considered the sun gear tooth crack and bearing clearance simultaneously to analyze their combined effect on vibration characteristics of planetary gearboxes. In this paper, a dynamic model is developed for planetary gearboxes considering the clearance of planet gear, sun gear, and carrier bearings, as well as sun gear tooth crack levels. Bearing forces are calculated considering bearing clearance, and the dynamic model equations are updated accordingly. The results reveal that the combination of bearing clearances can affect the vibration response with sun gear tooth crack by increasing the kurtosis. It is found that the effect of planet gear bearing clearance is very small, while the sun gear and carrier bearing clearance has clear impact on the vibration responses. These findings suggest that the incorporation of bearing clearance is important for planetary gearbox dynamic modeling.

Vasculoprotective endothelium glycocalyx (GCX) shedding plays a critical role in vascular disease. Previous work demonstrated that GCX degradation disrupts endothelial cell (EC) gap junction connexin (Cx) proteins, likely blocking interendothelial molecular transport that maintains EC and vascular tissue homeostasis to resist disease. Here, we focused on GCX regeneration and tested the hypothesis that vasculoprotective EC function can be stimulated via replacement of GCX when it is shed. We used EC with [i] intact heparan sulfate (HS), the most abundant GCX component; [ii] degraded HS; or [iii] HS that was restored after enzyme degradation, by cellular self-recovery or artificially. Artificial HS restoration was achieved via treatment with exogenous HS, with or without the GCX regenerator and protector sphingosine 1- phosphate (S1P). In these cells we immunocytochemically examined expression of Cx isotype 43 (Cx43) at EC borders and characterized Cx-containing gap junction activity by measuring interendothelial spread of gap junction permeable Lucifer Yellow dye. With intact HS, 60% of EC borders expressed Cx43 and dye spread to 2.88 ± 0.09 neighboring cells. HS degradation decreased Cx43 expression to 30% and reduced dye spread to 1.87± 0.06 cells. Cellular self-recovery of HS restored baseline levels of Cx43 and dye transfer. Artificial HS recovery with exogenous HS partially restored Cx43 expression to 46% and yielded dye spread to only 1.03 ± 0.07 cells. Treatment with both HS and S1P, recovered HS and restored Cx43 to 56% with significant dye transfer to 3.96 ± 0.23 cells. This is the first evidence of GCX regeneration in a manner that effectively restores vasculoprotective EC communication.

Maintenance optimization has received special attention among the wind energy research community over the past two decades. This is mainly because of the high degree of uncertainties involved in the execution of operation and maintenance (O&M) activities throughout the lifecycle of wind farms. The increasing complexity in offshore maintenance execution demands applied research and brings forth a need to develop problem-specific maintenance decision-making models. In this paper, a mathematical model is proposed to assist wind farm stakeholders in making critical resource- related decisions for corrective maintenance at offshore wind farms (OWFs), considering uncertainties in turbine failure information.

Natural and artificial cells are two common chassis in synthetic biology. Natural cells can perform complex tasks through synthetic genetic constructs, but their autonomous replication often causes safety concerns for biomedical applications. In contrast, artificial cells based on nonreplicating materials, albeit possessing reduced biochemical complexity, provide more defined and controllable functions. Here, for the first time, the authors create hybrid material-cell entities termed Cyborg Cells. To create Cyborg Cells, a synthetic polymer network is assembled inside each bacterium, rendering them incapable of dividing. Cyborg Cells preserve essential functions, including cellular metabolism, motility, protein synthesis, and compatibility with genetic circuits. Cyborg Cells also acquire new abilities to resist stressors that otherwise kill natural cells. Finally, the authors demonstrate the therapeutic potential by showing invasion into cancer cells. This work establishes a new paradigm in cellular bioengineering by exploiting a combination of intracellular man-made polymers and their interaction with the protein networks of living cells.

Patients and a mouse model of Batten disease, the juvenile form of neuronal ceroid lipofuscinosis (JNCL), raise autoantibodies against GAD65 and other brain-directed antigens. Here we investigate the adaptive component of the neuroimmune response. Cln3−/− mice have autoantibodies to GAD65 in their cerebrospinal fluid and elevated levels of brain bound immunoglobulin G (IgG). IgG deposition was found within human JNCL autopsy material, a feature that became more evident with increased age in Cln3−/− mice. The lymphocyte infiltration present in human and murine JNCL occurred late in disease progression, and was not capable of central/intrathecal IgG production. In contrast, we found evidence for an early systemic immune dysregulation in Cln3−/− mice. In addition evidence for a size-selective breach in the blood–brain barrier integrity in these mice suggests that systemically produced autoantibodies can access the JNCL central nervous system and contribute to a progressive inflammatory response.

Gears are widely used in gearbox to transmit power from one shaft to another. Gear crack is one of the most frequent gear fault modes found in industry. Identification of different gear crack levels is beneficial in preventing any unexpected machine breakdown and reducing economic loss because gear crack leads to gear tooth breakage. In this paper, an intelligent fault diagnosis method for identification of different gear crack levels under different working conditions is proposed. First, superhigh-dimensional statistical features are extracted from continuous wavelet transform at different scales. The number of the statistical features extracted by using the proposed method is 920 so that the extracted statistical features are superhigh dimensional. To reduce the dimensionality of the extracted statistical features and generate new significant low-dimensional statistical features, a simple and effective method called principal component analysis is used. To further improve identification accuracies of different gear crack levels under different working conditions, support vector machine is employed. Three experiments are investigated to show the superiority of the proposed method. Comparisons with other existing gear crack level identification methods are conducted. The results show that the proposed method has the highest identification accuracies among all existing methods.

The structural changes which occur during the swelling of Wyoming Na montmorillonite have been investigated by adsorption and desorption of water, simulation of XRD powder patterns, immersion microcalorimetry, and small-angle X-ray scattering in 10 to the power of (-3) N NaCl solutions. The progressive changes of the water concentration in the interlamellar space, and the mechanisms of water adsorption were followed from dry state to relative pressures up to 0. 9. The microstructure of Na montmorillonite corresponding to high water contents appears to be a network of quasi-crystals containing pores of about 1 µm in size. The tactoids were found to consist of a few layers and the water was mainly located in the layers inside the tactoids. Les changements de structure qui se produisent durant le gonflement de la montmorillonite Na du Wyoming ont été étudiés par différents procédés : adsorption et désorption d'eau, simulation de diagrammes de diffraction, microcalorimétrie d'immersion, et diffusion aux petits angles des rayons X dans des solutions de 10 puissance (-3) N NaCI. Les modifications progressives de la concentration d'eau dans l'espace interfoliaire, et les mécanismes de l'adsorption d'eau ont été suivis de l'état sec jusqu'à des pressions relatives atteignant 0,9. Pour de fortes teneurs en eau, la microstructure de la montmorillonite Na semble être un réseau de quasi-cristaux avec des pores d'environ 1 µm. On a constaté que les tactoïdes se composent de quelques feuillets, à l'intérieur desquels l'eau était principalement concentrée.

Planetary gearbox vibration signals have strong modulation features due to the amplitude modulation and frequency modulation (AM-FM) effect of gear faults, as well as the amplitude modulation (AM) effect of time-varying vibration transfer paths, on gear meshing vibrations. This results in an involute sidebands structure in Fourier spectrum, possibly misleading fault diagnosis. The modulating frequency of both amplitude modulation (AM) and frequency modulation (FM) parts is closely related to the gear fault characteristic frequency. This inspires the idea of joint amplitude and frequency demodulation analysis, thus addressing the complex sidebands issue inherent in Fourier spectrum. Demodulation analysis requires mono-component signals for accurate estimation of instantaneous frequency, and proper selection of an AM-FM component sensitive to gear fault. To this end, we firstly decompose the complex signal into intrinsic mode functions (IMFs) via variational mode decomposition (VMD), by exploiting its capability in decomposing complex modulated signal into constituent AM-FM components. For effective application of VMD in complex planetary gearbox signal analysis, we propose a method to determine a key parameter in VMD, i.e. the number of IMFs to be separated. For accurate instantaneous frequency estimation, we decompose IMFs via empirical AM-FM decomposition, to remove the influence of AM on instantaneous frequency estimation. Then, we select the sensitive IMF that contains the main gear fault information for further demodulation analysis. In order to properly select the sensitive IMF, we propose a criterion based on the gear vibration characteristics and the VMD properties. Finally, we obtain the amplitude and frequency demodulated spectra by applying Fourier transform to the amplitude envelope and instantaneous frequency of the selected sensitive IMF. According to the characteristics exhibited in the demodulated spectra, we can detect planetary gearbox fault. The proposed method is illustrated via a numerical simulated planetary gearbox vibration signal, and is further validated using lab experimental vibration signals of a planetary gearbox. Faults on all the three types of gear (sun, planet and ring) are successfully identified.

The pleiotropic serine/threonine protein kinase CK2 was the first kinase discovered. It is renowned for its role in cell proliferation and anti-apoptosis. The complexity of this kinase is well reflected by the findings of past decades in terms of its heterotetrameric structure, subcellular location, constitutive activity and the extensive catalogue of substrates. With the advent of non-biased high-throughput functional genomics such as genome-wide deletion mutant screening, novel aspects of CK2 functionality have been revealed. Our recent discoveries using the model organism Saccharomyces cerevisiae and mammalian cells demonstrate that CK2 regulates metal toxicity. Extensive literature search reveals that there are few but elegant works on the role of CK2 in regulating the sodium and zinc channels. As both CK2 and metal ions are key players in cell biology and oncogenesis, understanding the details of CK2’s regulation of metal ion homeostasis has a direct bearing on cancer research. In this review, we aim to garner the recent data and gain insights into the role of CK2 in metal ion transport.

To evaluate the prevalence and predictors of vitamin D insufficiency (VDI) in children in Great Britain.A nationally representative cross-sectional study survey of children (1102) aged 4-18 years (999 white, 570 male) living in private households (January 1997-1998). Interventions provided information about dietary habits, physical activity, socio-demographics, and blood sample. Outcome measures were vitamin D insufficiency (2.5 hours of TV/day/week (OR = 1.6[95%CI 1.0-2.4]).We confirm a previously under-recognised risk of VDI in adolescents. The marked higher risk for VDI in non-white children suggests they should be targeted in any preventative strategies. The association of higher risk of VDI among children who exercised less outdoors, watched more TV and were overweight highlights potentially modifiable risk factors. Clearer guidelines and an increased awareness especially in adolescents are needed, as there are no recommendations for vitamin D supplementation in older children.