52 research outputs found

    Ladle Metallurgy using the Scandinavian Lancers System

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    The Scandinavian Lancers Ladle Injection Metallurgy System is a metallurgical process that was developed jointly by Scandinavian steel industry and MEFOS, a foundation for metallurgical research located in Sweden. The development work was initiated in 1972 with MEFOS studying the fundamental principles of ladle injection. Considerable study was done on turbulence phenomena in agitated ladles, heat, mass and momentum transfer.Once the fundamental principles were under-stood, laboratory tests were conducted in 6-10 ton heats to evaluate the metallurgical results of injecting various powders. At this point the test work was moved to producing plants to determine that the theory and laboratory results could be obtained under actual operating conditions

    NOGO-A induction and localization during chick brain development indicate a role disparate from neurite outgrowth inhibition

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    BACKGROUND: Nogo-A, a myelin-associated protein, inhibits neurite outgrowth and abates regeneration in the adult vertebrate central nervous system (CNS) and may play a role in maintaining neural pathways once established. However, the presence of Nogo-A during early CNS development is counterintuitive and hints at an additional role for Nogo-A beyond neurite inhibition. RESULTS: We isolated chicken NOGO-A and determined its sequence. A multiple alignment of the amino acid sequence across divergent species, identified five previously undescribed, Nogo-A specific conserved regions that may be relevant for development. NOGO gene transcripts (NOGO-A, NOGO-B and NOGO-C) were differentially expressed in the CNS during development and a second NOGO-A splice variant was identified. We further localized NOGO-A expression during key phases of CNS development by in situ hybridization. CNS-associated NOGO-A was induced coincident with neural plate formation and up-regulated by FGF in the transformation of non-neural ectoderm into neural precursors. NOGO-A expression was diffuse in the neuroectoderm during the early proliferative phase of development, and migration, but localized to large projection neurons of the optic tectum and tectal-associated nuclei during architectural differentiation, lamination and network establishment. CONCLUSION: These data suggest Nogo-A plays a functional role in the determination of neural identity and/or differentiation and also appears to play a later role in the networking of large projection neurons during neurite formation and synaptogenesis. These data indicate that Nogo-A is a multifunctional protein with additional roles during CNS development that are disparate from its later role of neurite outgrowth inhibition in the adult CNS

    Newborn screening in metachromatic leukodystrophy – European consensus-based recommendations on clinical management

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    Introduction: Metachromatic leukodystrophy (MLD) is a rare autosomal recessive lysosomal storage disorder resulting from arylsulfatase A enzyme deficiency, leading to toxic sulfatide accumulation. As a result affected individuals exhibit progressive neurodegeneration. Treatments such as hematopoietic stem cell transplantation (HSCT) and gene therapy are effective when administered pre-symptomatically. Newborn screening (NBS) for MLD has recently been shown to be technically feasible and is indicated because of available treatment options. However, there is a lack of guidance on how to monitor and manage identified cases. This study aims to establish consensus among international experts in MLD and patient advocates on clinical management for NBS-identified MLD cases. Methods: A real-time Delphi procedure using eDELPHI software with 22 experts in MLD was performed. Questions, based on a literature review and workshops, were answered during a seven-week period. Three levels of consensus were defined: A) 100%, B) 75–99%, and C) 50–74% or >75% but >25% neutral votes. Recommendations were categorized by agreement level, from strongly recommended to suggested. Patient advocates participated in discussions and were involved in the final consensus. Results: The study presents 57 statements guiding clinical management of NBS-identified MLD patients. Key recommendations include timely communication by MLD experts with identified families, treating early-onset MLD with gene therapy and late-onset MLD with HSCT, as well as pre-treatment monitoring schemes. Specific knowledge gaps were identified, urging prioritized research for future evidence-based guidelines. Discussion: Consensus-based recommendations for NBS in MLD will enhance harmonized management and facilitate integration in national screening programs. Structured data collection and monitoring of screening programs are crucial for evidence generation and future guideline development. Involving patient representatives in the development of recommendations seems essential for NBS programs

    Integrated genomic characterization of pancreatic ductal adenocarcinoma

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    We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

    Increasing Stringiness of Low Fat Mozzarella Cheese Using Polysaccharides

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    We examined the ability of polysaccharides to function as fat mimetics in low-fat (LF) mozzarella string cheese to improve functionality by acting like fat globules to separate protein fibers during cheese extrusion. Low-fat mozzarella cheese curd made from 273 kg of 0.7% fat milk was salted at a rate of 10 g/kg then divided into 3.6-kg batches that were hand-stretched in 5% brine at 80° C and formed into a homogeneous mass. The hot cheese was hand mixed with a hot 80° polysaccharide slurry, placed into a small piston-driven extruder and then forced through a 16-mm die to form the string cheese. Extruded string cheese was cut manually into approximately 15-cm lengths. From preliminary trials using starches (waxy corn, waxy rice, and instant tapioca starch), xanthan and guar gums, and polydextrose, we determined that LF string cheese made using xanthan gum most closely resembled commercial string cheese. LF cheese was then made using a 10% xanthan gum slurry added at 0.25%, 0.5%, 1.0%, 1.5%, and 2.0% (wt/wt) levels. Cheeses were analyzed for fat, salt, pH, and moisture. After 2 wk of 4° C storage, the cheese was analyzed for extent of stringiness by pulling apart the cheese longitudinally, visually observing and photographing the size, length and appearance of individual strings of cheese. Hardness was determined using a Warner-Bratzler shear test. A consumer liking test was conducted after 2 and 8 wk storage time at 6° C. At 2-wk storage, using a hedonic scale (1 to 9) for overall liking, the LF string cheese with 1% added xanthan slurry (score = 6.8) was liked more (PWhen considered on a JAR scale, most of the panelists scored the LF cheese with added xanthan gum (1%) as having the right texture, while only some did so for the retail cheese. The LF control cheese with no added gum was considered too firm. Using a visual comparison, adding the xanthan gum slurry produced greater fiber formation with the longest and most complete string separation. After 8 wk storage, the LF cheeses had softened extensively with fracture stress for LF cheese decreasing from 12 to 20 kg at 2 wk to 1.5 to 3 kg at 8 wk. Extent of stringiness also decreased during storage
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