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In this study, a hybrid dual drug-loaded hydroxyapatite-oxidized dextran methacrylate core–shell nanocarrier was formulated and explored for combinatorial delivery of doxorubicin (DOX) and methotrexate (MTX) to bone cancer. The synthesized nanocarrier was well characterized by different techniques. In vitro drug release studies in both acidic (pH 5) and alkaline (pH 7.4) conditions showed sequential release of MTX followed by DOX in a sustained manner for 10 days. Biocompatibility and cytotoxicity studies performed using drug-loaded nanoparticles (NPs) on fibroblast L929 cells and osteosarcoma MG63 cells (OMG63) showed that the NPs were highly biocompatible and showed concentration-dependent toxicity. Gene expression studies in OMG-63 cells exhibited the upregulation of caspase-3 and BAX which confirmed the apoptosis induced by dual drug-loaded NPs. The nanocarrier is expected to be a potential bone void filling material, as well as a platform for sequential delivery of DOX and MTX for the treatment of bone cancer.
Air plasma sprayed thermal barrier coatings (TBCs) are used extensively throughout the gas turbine industry for both power and propulsion. As these engines push to higher temperatures, concern for failure from the melt infiltration of ingested siliceous debris [commonly called calcium–magnesium–alumino-silicate (CMAS)] arises, especially in aeroengines. 7 wt% yttria-stabilized zirconia is particularly prone to melt infiltration and stiffening-induced premature failure. Novel TBC materials such as gadolinium zirconate have been introduced for their infiltration-inhibiting CMAS reactions. Past academic work has utilized ideal laboratory furnace environments to study these phenomena. In this work, the influence of TBC microstructure and chemistry on impinging molten CMAS injected via a burner rig is studied. An observational study of the impacted surfaces and location-specific cross-sectional analysis is reported. Results point toward the critical role of surface microstructure on the mobility and reactivity of the molten CMAS.
Giant cell tumor (GCT) of bone is a common benign lesion that causes significant morbidity due to the failure of modern medical and surgical treatment. Surface ultra-structures of giant cells (GCs) may help in distinguishing aggressive tumors from indolent GC lesions. This study aimed to standardize scanning electron microscopic (SEM) imaging of GC from GCT of bone. Fresh GCT collected in Dulbecco's Modified Eagle Medium was washed to remove blood, homogenized, or treated with collagenase to isolate the GCs. Mechanically homogenized and collagenase-digested GCs were imaged on SEM after commonly used drying methodologies such as air-drying, tetramethylsilane (TMS)-drying, freeze-drying, and critical point-drying (CPD) for the optimization of sample processing. The collagenase-treated samples yielded a greater number of isolated GC and showed better surface morphology in comparison to mechanical homogenization. Air-drying was associated with marked cell shrinkage, and freeze-dried samples showed severe cell damage. TMS methodology partially preserved the cell contour and surface structures, although the cell shape was distorted. GC images with optimum surface morphology including membrane folding and microvesicular structures on the surface were observed only in collagenase-treated and critical point-dried samples. Collagenase digestion and critical point/TMS-drying should be performed for optimal SEM imaging of individual GCs.
The current fourth industrial revolution, or ‘Industry 4.0’ (I4.0), is driven by digital data, connectivity, and cyber systems, and it has the potential to create impressive/new business opportunities. With the arrival of I4.0, the scenario of various intelligent systems interacting reliably and securely with each other becomes a reality which technical systems need to address. One major aspect of I4.0 is to adopt a coherent approach for the semantic communication in between multiple intelligent systems, which include human and artificial (software or hardware) agents. For this purpose, ontologies can provide the solution by formalizing the smart manufacturing knowledge in an interoperable way. Hence, this paper presents the few existing ontologies for I4.0, along with the current state of the standardization effort in the factory 4.0 domain and examples of real-world scenarios for I4.0.
A Cu–3%Ti (wt%) alloy was processed by multiaxial forging (MAF) at cryogenic temperature up to 3 cycles, imposing a total strain of 1.6. Microstructure and mechanical properties of the unprocessed and cryo-forged samples were analyzed. X-ray diffraction results showed deviation in peak broadening and peak intensity of the cryo-forged samples in comparison to that of unprocessed, which are due to texture modification caused by grain refinement during the MAF process. Microstructural analysis showed reduction in grain size from 80 µm in the as-received condition to 250 nm after 3 cycles. Electron backscatter diffraction results indicated the transformation of high angle grain boundaries to low angle grain boundaries in all 3 cycles when compared to the as-received condition. Reduction in ductility was observed after 1 cycle, but with an increase in the number of cycles, both strength and ductility increased. After 3 cycles, ultimate tensile strength and hardness reached 1126 MPa and 427 Hv as compared to 528 MPa and 224 Hv for the as-received condition. Fractography analysis showed decrement in dimple size after 1 cycle, in comparison to that of the as-received condition. However, it kept on increasing for higher number of cycles.
OBJECTIVES/SPECIFIC AIMS: The goals of our study are: (1) To test the hypothesis that the presence of any autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with decreased risk of developing LN. (1b) To test the hypothesis that there is a lower risk of LN in patients with cSLE and any co-existing autoimmune cytopenia (ITP, AIHA, or ES) who had treatment with immunomodulatory or immunosuppressive therapy (intravenous immunoglobulin, corticosteroids, rituximab, or cyclophosphamide) before diagnosis of cSLE. (2) To test the hypothesis that in patients with cSLE who develop LN, the presence of any co-existing autoimmune cytopenia (ITP, AIHA, or ES) at time of cSLE diagnosis is associated with less severe LN. (3) To test the hypothesis that at the time of cSLE diagnosis, there is a lower incidence of double-stranded DNA (dsDNA) and a higher incidence of ribonucleoprotein autoantibodies in those with co-existing autoimmune cytopenias (ITP, AIHA, or ES). METHODS/STUDY POPULATION: This is a retrospective study of a large cohort of patients from the Emory Children’s Center, Children’s Healthcare of Atlanta (CHOA) satellite clinics and pediatric rheumatology inpatient services at any of the 3 CHOA hospitals (Egleston, Scottish Rite, and Hughes Spalding) with ICD 9 or ICD 10 codes corresponding to a diagnosis of SLE between January 1, 2000 and January 31, 2015. We will include patients diagnosed at age 2–16 years who meet at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE. We will consider these patients as having cSLE. We will exclude patients with less than 2 years of follow-up data and patients with a pre-existing diagnosis of cSLE who transferred care to our Emory/CHOA center. We will define time of diagnosis as time from initial evaluation for cSLE by a pediatric rheumatologist up to 28 days post cSLE diagnosis. We will define co-existing autoimmune cytopenia as preceding diagnosis of a primary autoimmune cytopenia or the presence of an autoimmune cytopenia at the time of initial evaluation for cSLE and up to 28 days post cSLE diagnosis. We will define AIHA as hemoglobin ≤10 g/dL with positive direct Coombs and/or reticulocytosis. We will define ITP as thrombocytopenia <100,000/mm3 and Evans syndrome as concurrent or sequential AIHA and ITP. We will define lupus nephritis (LN) as the presence of urine protein to creatinine ratio>0.5 in a patient with cSLE and/or biopsy demonstrating LN. IRB approval of the study protocol with waiver of informed consent has been obtained from the CHOA IRB. RESULTS/ANTICIPATED RESULTS: We have approximately 40 newly diagnosed cSLE patients annually; therefore, a study population of 400 patients with cSLE is possible. Therefore, assuming 50% of cSLE patients without autoimmune cytopenias have LN and 22% of cSLE patients with autoimmune cytopenias have LN, at an alpha of 0.05, we will have > 80% power to detect significant differences. We expect to show phenotypic differences in patients with co-existing autoimmune cytopenia and cSLE from other newly diagnosed cSLE patients. We expect that the presence of a co-existing autoimmune cytopenia and cSLE is associated with decreased risk of developing LN. We expect that there will be a decreased prevalence of LN in cSLE patients pretreated with immunosuppression further highlighting that earlier indicators of LN risk and early interventions are necessary. We expect to find decreased severity of LN in patients with a co-existing autoimmune cytopenia at time of cSLE diagnosis. DISCUSSION/SIGNIFICANCE OF IMPACT: Our study will be conducted on one of the largest single-center cohorts of cSLE patients. We will determine whether pediatric patients with SLE and autoimmune cytopenias have a distinct clinical or serological phenotype and less severe disease. Our results will be significant in developing hypothesis for further retrospective or prospective multi-center or large database and immunological studies to understand the relationship of each individual autoimmune cytopenia to cSLE. It will provide the necessary background for further clinical and immunological studies to identify predictive biomarkers of cSLE severity.
A cadmium chloride activation treatment is essential for the production of high efficiency cadmium telluride (CdTe) solar cells. However, the effects of the treatment on the distributions of chlorine and sulphur within the device are not fully understood. Here, the detailed locations of chlorine and sulphur in a treated CdTe cell are determined in three dimensions by high resolution dynamic SIMS measurements. Chlorine is found to be present in grain boundaries, grain interiors, extended defects within the grain interiors, at the front interface, and in the cadmium sulphide layer. In each of these regions, the chlorine is likely to have significant effects on local electronic properties of the material, and hence overall device performance. Sulphur is found to have a U-shaped diffusion profile within CdTe grains, indicating a mixed grain boundary and lattice diffusion regime.
Internet applications have been extended to various aspects of everyday life and offer services of high reliability and security at relatively low cost. This project presents the design of a reliable, safe and secure software system for real-time remote operation and monitoring of an aero gas turbine with utilisation of existing internet technology, whilst the gas turbine is installed in a remote test facility
This project introduces a capability that allows remote and flexible operation of an aero gas turbine throughout the whole operational envelope, as required by the user at low cost, by exploiting the available Internet technology. Remote operation of the gas turbine can be combined with other remote Internet applications to provide very powerful gas-turbine performance-simulation experimental platforms and real-time performance monitoring tools, whilst keeping the implementation cost at low levels.
The gas turbine used in this experiment is an AMT Netherlands Olympus micro gas turbine and a spiral model approach was applied for the software. The whole process was driven by risk mitigation.
The outcome is a fully functional software application that enables remote operation of the micro gas turbine whilst constantly monitors the performance of the engine according to basic gas turbine control theory. The application is very flexible, as it runs with no local installation requirements and includes provisions for expansion and collaboration with other online performance simulation and diagnostic tools.
In vitro rumen methane output (IRMO) of over 200 feed/feed mix samples representing approximately 74 feed types was investigated in a series of completely randomized experiments. The samples comprised dry fodder, grass, tree leaves, cultivated grasses, cereal by-products, cereal grains, oilseed/meals, compound feeds and total mixed rations (TMRs) from the tropical regions. These samples were subjected to three in vitro gas production tests at 39 °C in 100 ml Heberle syringes. The first incubation was conducted with 200 mg dry matter (DM) substrate for 96 h to determine half-time gas production (t1/2, h) value of each sample. The second and third incubations were carried out simultaneously. The second incubation was done with 200 mg DM substrate until t1/2 time to determine IRMO and third with 500 mg DM to estimate in vitro dry matter digestibility (IVDMD) of each samples, respectively. The IRMO was expressed as ml/100 mg digestible substrate. Crude protein content (g/kg DM) was lowest in dry fodder samples and highest in oilseed meals, whereas it was similar in local grass and tree leaves. The IVDMD values ranged from 0·48 to 0·87; the lowest digestibility was recorded in tree leaves. The potential gas production (PGP, ml/200 mg DM) ranged from 9·76 to 61·3. The PGP from grasses and compound feeds was similar, whereas it was lowest in tree leaves. The rate constant (mg/h) was maximum in compound feed followed by oilseed meal. The rate constant was similar among other group of feedstuffs. The t1/2 time ranged from 9·8 to 19·4 h. The highest t1/2 time was recorded in local grass samples followed by dry fodder and cultivated grasses. However, they were similar among tree leaves, cereal grains, by-products and compound feeds. The methane % in the total gas varied from 9·79 (tree leaves) to 20·2 (local grasses). Among straw, IRMO varied from 3·88 (Zea mays fodder) to 12·0 (Sorghum vulgare) and it was lower in fruit tree leaves than cultivated grasses. Among protein and energy sources, IRMO was higher in cereal by-products as compared with cereal grains, oil meals and compound feed. The IRMO was similar among TMR, irrespective of the composition of the concentrate mixture. Nevertheless, it varied with the amount of concentrate in the TMR. This is the first exhaustive data on IRMO from the tropical region. Because of the substantial amount of dietary gross energy lost in methane, knowledge of the methane output from these feed ingredients will help in formulating low methane emitting diets for ruminants. Incorporation of tropical tree leaves in the diets and feeding TMR are potential strategies to reduce enteric methane emission in ruminants.