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Carbon nanotube (CNT)/thermoplastic composites have many potential applications. However, processing CNT/thermoplastic composites has been extremely challenging due to the inherently strong affinity of CNT to themselves. Two major issues in processing CNT/thermoplastic composites for enhanced mechanical properties are achieving uniform dispersion and producing alignment of the nanotubes in the polymer matrix. This study used a combination of surfactant-aided mixing, extrusion, and various drawing processing techniques to successfully obtain significant improvement of nanotube dispersion and alignment in a semi-crystalline polymer matrix.

Equipment management has received significant attention during the recent years in the semiconductor industry because of the industry's dynamic characteristics and the increasing cost of capital equipment. The inefficiencies in equipment management have a greater impact on a company's output and profit. In many segments of the semiconductor industry, this situation is made worse because the technology becomes obsolete at a very rapid rate, causing a very short equipment useful life. Equipment is operated continuously and performs more and more complex tasks. As a result, managing equipment performance becomes a challenging task for managers in semiconductor companies. Equipment management has gone through the pre-maintenance era, which was the breakdown management phase in the pre-1950 period, and the maintenance era, which consisted of the preventive maintenance phase in the 1950s, the productive maintenance phase in the 1960s, the “Total Productive Maintenance” (TPM) phase in 1970s, and the TPM with predictive maintenance phase since the 1980s. Up until now, equipment management has been operated in the maintenance era at large. The conclusive focus of maintenance approaches is on the optimization of equipment availability. However, it is equipment utilization that determines the output and profit of a factory. The maintenance organizational structure is often based on a functional setup. The whole picture is often not fully comprehended, allowing inefficiencies to occur in the equipment management process. Because the maintenance methods cannot meet today's requirements, especially in the semiconductor industry, Intel started to challenge the old norms in equipment management and eliminated the functional division in maintenance. The equipment management process is consolidated under a single ownership. The maintenance departments are replaced by platform engineering departments with their responsibilities extended beyond maintenance to include equipment development as well as equipment utilization, and thus providing a total solution to optimizing equipment output. This dissertation research highlights this new era in equipment management as the “post-maintenance era” by utilizing the systems approach to examine the new era under the areas of environmental, goals and values, structural, technical psychosocial, and managerial subsystems. The platform convergence theory is proposed to signify this new paradigm shift in equipment management.

Diffusion is a major molecular transport mechanism in biological systems. Quantifying direction-dependent (i.e., anisotropic) diffusion is vitally important to depicting how the three-dimensional (3D) tissue structure and composition affect the biochemical environment, and thus define tissue functions. However, a tool for noninvasively measuring the 3D anisotropic extracellular diffusion of biorelevant molecules is not yet available. Here, we present light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP), which noninvasively determines 3D diffusion tensors of various biomolecules with diffusivities up to 51 µm 2 s −1 , reaching the physiological diffusivity range in most biological systems. Using cornea as an example, LiFT-FRAP reveals fundamental limitations of current invasive two-dimensional diffusion measurements, which have drawn controversial conclusions on extracellular diffusion in healthy and clinically treated tissues. Moreover, LiFT-FRAP demonstrates that tissue structural or compositional changes caused by diseases or scaffold fabrication yield direction-dependent diffusion changes. These results demonstrate LiFT-FRAP as a powerful platform technology for studying disease mechanisms, advancing clinical outcomes, and improving tissue engineering. It is challenging to quantify anisotropic diffusion in biological systems. Here the authors report light-sheet imaging-based Fourier transform fluorescence recovery after photobleaching (LiFT-FRAP) to noninvasively determine 3D diffusion tensors of various biomolecules at physiological diffusivity.

The escalating worldwide prevalence of Crohn’s disease (CD) among children and adolescents, coupled with a trend toward earlier onset, presents significant challenges for healthcare systems. Moreover, the chronicity of this condition imposes substantial individual burdens. Consequently, the principal objective of CD treatment revolves around rapid inducing remission. This study scrutinizes the impact of age, gender, initial disease localization, and therapy on the duration to achieve disease activity amelioration. Data from the Saxon Pediatric IBD Registry in Germany were analyzed over a period of 15 years. In addition to descriptive methods, logistic and linear regression analyses were conducted to identify correlations. Furthermore, survival analyses and Cox regressions were utilized to identify factors influencing the time to improvement in disease activity. These effects were expressed as Hazard Ratios (HR) with 95% confidence intervals. Data on the clinical course of 338 children and adolescents with CD were available in the registry. The analyses showed a significant correlation between a young age of onset and the severity of disease activity. It was evident that treatment with anti-TNF (Infliximab) was associated with a more favorable prognosis in terms of the time required for improvement in disease activity. Similarly, favorable outcomes were observed with the combination therapies of infliximab with enteral nutrition therapy and Infliximab with immunosuppressants. Conclusion : Our analysis of data from the Saxon Pediatric IBD Registry revealed that the timeframe for improvement of disease activity in pediatric Crohn’s disease is influenced by several factors. Specifically, patient age, treatment modality, and initial site of inflammation were found to be significant factors. The study provides important findings that underline the need for individualized treatment.

The clinical role and underlying mechanisms of valproic acid (VPA) on bone homeostasis remain controversial. Herein, we confirmed that VPA treatment was associated with decreased bone mass and bone mineral density (BMD) in both patients and mice. This effect was attributed to VPA-induced elevation in osteoclast formation and activity. Through RNA-sequencing, we observed a significant rise in precursor miR-6359 expression in VPA-treated osteoclast precursors in vitro, and further, a marked upregulation of mature miR-6359 (miR-6359) in vivo was demonstrated using quantitative real-time PCR (qRT-PCR) and miR-6359 fluorescent in situ hybridization (miR-6359-FISH). Specifically, the miR-6359 was predominantly increased in osteoclast precursors and macrophages but not in neutrophils, T lymphocytes, monocytes and bone marrow-derived mesenchymal stem cells (BMSCs) following VPA stimulation, which influenced osteoclast differentiation and bone-resorptive activity. Additionally, VPA-induced miR-6359 enrichment in osteoclast precursors enhanced reactive oxygen species (ROS) production by silencing the SIRT3 protein expression, followed by activation of the MAPK signaling pathway, which enhanced osteoclast formation and activity, thereby accelerating bone loss. Currently, there are no medications that can effectively treat VPA-induced bone loss. Therefore, we constructed engineered small extracellular vesicles (E-sEVs) targeting osteoclast precursors in bone and naturally carrying anti-miR-6359 by introducing of EXOmotif (CGGGAGC) in the 3’-end of the anti-miR-6359 sequence. We confirmed that the E-sEVs exhibited decent bone/osteoclast precursor targeting and exerted protective therapeutic effects on VPA-induced bone loss, but not on ovariectomy (OVX) and glucocorticoid-induced osteoporotic models, deepening our understanding of the underlying mechanism and treatment strategies for VPA-induced bone loss.

Purpose Telemedicine provides patients with easy and remote access to consultant expertise irrespective of geographic location. In a randomized controlled trial, this study has applied a rigorous costing methodology to the use of telemedicine in chronic pain management. Methods We performed a randomized two-period crossover trial comparing in-person (IP) consultation with telemedicine (TM) consultation in the management of chronic pain. Over an 18-month period, 26 patients each completed two diaries capturing their direct and indirect travel costs, daily pain scores, and satisfaction with physician consultation. Costing models were developed to account for direct, indirect, fixed, and variable costs in order to perform break-even analyses. Sensitivity analysis was performed over a broad range of assumptions. Results Direct patient costs were significantly lower in the TM group than in the IP group, with median cost and interquartile range $133 (28–377) vs $443 (292–1075), respectively ( P  = 0.001). More patients were highly satisfied with the TM consultation than with the IP consultation (56 and 24%, respectively; P  < 0.05). Break-even annual patient volume was estimated at 57 patients. A two-way sensitivity analysis controlling for annual patient volume and round-trip distance indicated that TM remains cost-effective at volumes >50 patients/year or at round-trip distances >200 km. Conclusion Telemedicine is cost-effective over a broad range of assumptions, including annual patient volumes, travel distance, fuel costs, amortization, and discount rates. This study provides data from a real-world setting to determine relevant thresholds and targets for establishing a TM program for patients who are undergoing chronic pain therapy.

Fuzzy logic has features that are particular attractive in light of the problems posed by autonomous robot navigation. Fuzzy logic allows us to model different types of uncertainty and imprecision. In this paper, the implementation of a hexapod mobile robot with a fuzzy controller navigating in unknown environments is presented. The robot, MKIII, interprets input sensor data through the comparison of values in its fuzzy rule base and moves accordingly to avoid obstacles. Results of trial run experiments are presented.

Developing high-resolution reference maps of disease-susceptible spatial niches is a critical step to mitigating the profound effects of lung disease. Here, we present an integrated multimodal single-nucleus human lung atlas (snHLA) profiling 746,047 nuclei from 49 mapped lung blocks spanning clinically relevant distal airways, alveoli, and interstitium across 11 healthy adults. Integrating snRNA-seq and SNARE-seq2, which co-assays chromatin accessibility and gene expression from the same nucleus, we resolved 70 molecularly distinct populations and captured 332,846 accessible chromatin regions, nominating new transcriptional regulators of human lung cell diversity. Spatial transcriptomics using MERFISH mapped 25 cell populations across 7 structural neighborhoods and multiplexed immunofluorescence localized cell subtypes and distal airway-defining protein markers, expanding and validating distinct lung structure-specific cell populations. This open access snHLA and companion Cell Type and Marker Gene Dictionary with anatomically aligned nomenclature delivers a foundational resource at an unprecedented resolution to interrogate the origins of lung pathophysiology.

RationaleAcute lung injury alters ventilatory control by impairing gas exchange. However, even before hypoxemia develops, lung inflammation itself may alter ventilatory control. The objective of the present study was to examine the impact of acute lung injury on ventilatory control by hypoxia and hypercapnia.MethodsExperiments were performed on adult male Sprague-Dawley rats challenged with intratracheal injections of either bleomycin (BM; 1 unit) or PBS. Five days after the injections, the extent of lung injury was evaluated, and ventilatory responses to hypoxia (12% O2) or hypercapnia (7% CO2) were measured by plethysmography in unanesthetized animals and by diaphragmatic EMG in anesthetized animals. Contribution of carotid body sensory afferents to ventilatory patterns was evaluated by comparing responses before and after glomectomy in anesthetized animals.ResultsBM-treated animals had increased total cell count, percent neutrophils, and protein levels in lavage fluid with no alterations in lung collagen content suggesting acute lung injury but not fibrosis. Core body temperature, PaO2 , and PaCO2 were comparable between both groups of animals. In unanesthetized animals (n = 16), baseline ventilation and the hypoxic ventilatory responses were significantly higher in BM-injected animals compared to control animals (average increases in minute ventilation [VE]: BM +214 ± 59 mL/kg/min vs Control +60 ± 8 mL/kg/min; p = .003), whereas respiratory stimulation by hypercapnia was not altered to the same degree (p = .672). The selective enhancement of hypoxic ventilatory drive was also present in anesthetized, spontaneously breathing animals (n = 12) where average increases in respiratory rate [RR] were greater in animals with lung injury (p = .036). In contrast, this difference between control and BM-exposed animals was abolished following bilateral glomectomy (p = .786). In these same animals, average decreases in RR in response to sudden administration of hyperoxia (FiO2 change from 0.12'1.0) was significantly greater in the BM-exposed group compared to control animals (BM -13.0 ± 1.0 % vs control -9.7 ± 1.0 %; p = .041), and these differences were abolished following glomectomy (p = .128).ConclusionsThese data demonstrate that afferent sensory input from the carotid body contributes to a selective enhancement of hypoxic ventilatory drive in the absence of pulmonary fibrosis and arterial hypoxemia in early BM-induced lung injury.