Strategies for obtaining deep slots in soft materials can vary significantly. Conventionally, the tool travels along the slot, removing material mainly with the side cutting edges. However, a “plunge ...milling” strategy is also possible, performing the cut vertically, taking advantage of the tip cutting edges that almost reach the center of the tool. Although both strategies are already commonly used, there is a clear gap in the literature in studies that compare tool wear, surface roughness, and productivity in each case. This paper describes an experimental study comparing the milling of deep slots in AA7050-T7451 aluminum alloy, coated with a novel DLCSiO500W3.5O2 layer to minimize the aluminum adhesion to the tool, using conventional and plunge milling strategies. The main novelty of this paper is to present a broad study regarding different factors involved in machining operations and comparing two distinct strategies using a novel tool coating in the milling of aeronautical aluminum alloy. Tool wear is correlated with the vibrations of the tools in each situation, the cycle time is compared between the cases studied, and the surface roughness of the machined surfaces is analyzed. This study concludes that the cycle time of plunge milling can be about 20% less than that of conventional milling procedures, favoring economic sustainability and modifying the wear observed on the tools. Plunge milling can increase productivity, does not increase tool tip wear, and avoids damaging the side edges of the tool, which can eventually be used for final finishing operations. Therefore, it can be said that the plunge milling strategy improves economic and environmental sustainability as it uses all the cutting edges of the tools in a more balanced way, with less global wear.
Germline mutations in codon 918 of exon 16 of the RET gene (M918T) are classically associated with multiple endocrine neoplasia type 2B (MEN 2B) with highly aggressive medullary thyroid cancer (MTC), ...pheochromocytoma and a unique phenotype. The objectives of this study are to describe the rare M918V RET mutation discovered in 8 MTC kindreds from Brazil lacking the MEN 2B phenotype classically observed in M918T patients and to investigate the presence of a founder effect for this germline mutation. Eight apparently sporadic MTC cases were diagnosed with the germline M918V RET mutation. Subsequently, their relatives underwent clinical and genetic assessment (n = 113), and M918V was found in 42 of them. Until today, 20/50 M918V carriers underwent thyroidectomy and all presented MTC/C-cell hyperplasia; the remainder carriers are on clinical follow-up. None of the M918V carriers presented clinical features of MEN 2B. Their clinical presentation was heterogeneous, and the age at tumor diagnosis ranged from 24 to 59 years. Lymph node metastases were present in 12/20 patients, and presumable distant metastases in 2/20; in contrast, we observed a carrier of up to 87 years of age without evidence of MTC. Ethnographic fieldwork and haplotype analyses suggested that the founder mutation first settled in that area fifteen generations ago and originated from Portugal. Our study is the first to demonstrate the RET M918V mutation co-segregating in 8 familial MTC kindreds with validated evidence of a founder effect. We suggest that M918V MTC should be clinically considered an American Thyroid Association (ATA) moderate-risk category.
Traumatic spinal cord injury (SCI) causes dramatic disability and dysfunction in the motor, sensory and autonomic systems. The severe inflammatory reaction that occurs after SCI is strongly ...associated with further tissue damage. As such, immunomodulatory strategies have been developed, aimed at reducing inflammation, but also at shaping the immune response in order to protect, repair and promote regeneration of spared neural tissue. One of those promising strategies is the intraspinal administration of the cytokine interleukin-4 (IL-4) that was shown to promote a phenotype on specific immune cells associated with neuroprotection and repair. In this work, we evaluated if a systemic delivery of IL-4 for a 7-days period was also capable of promoting neuroprotection after SCI by analyzing different neural cells populations and motor recovery. IL-4 treatment promoted an elevation of the anti-inflammatory cytokine IL-10 in the serum both at 24 h and 7 days after injury. Locally, treatment with IL-4 led to a reduction on cells expressing markers associated with inflammation, CD11b/c and iNOS. Importantly, IL-4 treatment increased the neuronal markers βIII-tubulin and NeuN, and the oligodendrocyte marker O4, suggesting a neuroprotective effect. Moreover, 100% of the animals treated with IL-4 were able to recover weight support against only 33% of saline treated animals. Overall, these results show that systemic administration of IL-4 positively impacts different aspects of spinal cord injury, creating a more favorable environment for recovery to take place.
Bone turnover markers (BTMs) are product of bone cell activity and are generally divided in bone formation and bone resorption markers. The purpose of this review was to structure the available ...information on the use of BTMs in studies on small ruminants, especially for monitoring their variations related to diet, exercise, gestation and metabolic lactation state, circadian and seasonal variations, and also during skeletal growth. Pre-clinical and translational studies using BTMs with sheep and goats as animal models in orthopaedic research studies to help in the evaluation of the fracture healing process and osteoporosis research are also described in this review. The available information from the reviewed studies was systematically organized in order to highlight the most promising BTMs in small ruminant research, as well as provide a wide view of the use of sheep and goat as animal models in orthopaedic research, type of markers and commercial assay kits with cross-reactivity in sheep and goat, method of sample and storage of serum and urine for bone turnover markers determination and the usefulness and limitations of bone turnover markers in the different studies, therefore an effective tool for researchers that seek answers to different questions while using BTMs in small ruminants.
The development of vaccines to prevent COVID-19 breakouts came with highly positive results but some unexpected side effects. Rare side effects have been seen with the BNT162b2 SARS-CoV 2 vaccine.
We ...present the case of a 45-year-old female patient who developed an acute kidney injury needing urgent hemodialysis one week after the second administration of the BNT162b2 SARS-CoV 2 vaccine. She developed a macular rash on her lower limbs and palms as well. A kidney biopsy was performed 10 days after vaccine inoculation, diagnosing acute interstitial nephritis and acute tubular necrosis with cellular casts. The patient was treated with three corticosteroid pulses followed by daily prednisolone. We witnessed clinical improvement 4 days after the initial corticosteroid treatment with progressive recovery of kidney function and hemodialysis withdrawal. After 2 weeks, the patient had recovered her kidney function. Immunophenotyping was performed, diagnosing a hypersensitivity to the vaccine and the polyethylene glycol excipient.
Patients may develop acute reactions to vaccines. In this case, symptoms seem to correlate significantly with its inoculation and, although this case had a favourable outcome, these side effects must be made aware for clinicians and patients.
Cellular systems implanted into an injured nerve may produce growth factors or extracellular matrix molecules, modulate the inflammatory process and eventually improve nerve regeneration. In the ...present study, we evaluated the therapeutic value of human umbilical cord matrix MSCs (HMSCs) on rat sciatic nerve after axonotmesis injury associated to Vivosorb® membrane. During HMSCs expansion and differentiation in neuroglial-like cells, the culture medium was collected at 48, 72 and 96h for nuclear magnetic resonance (NMR) analysis in order to evaluate the metabolic profile. To correlate the HMSCs ability to differentiate and survival capacity in the presence of the Vivosorb® membrane, the Ca2+i of undifferentiated HMSCs or neuroglial-differentiated HMSCs was determined by the epifluorescence technique using the Fura-2AM probe. The Vivosorb® membrane proved to be adequate and used as scaffold associated with undifferentiated HMSCs or neuroglial-differentiated HMSCs. In vivo testing was carried out in adult rats where a sciatic nerve axonotmesis injury was treated with undifferentiated HMSCs or neuroglial differentiated HMSCs with or without the Vivosorb® membrane. Motor and sensory functional recovery was evaluated throughout a healing period of 12 weeks using sciatic functional index (SFI), extensor postural thrust (EPT), and withdrawal reflex latency (WRL).
Stereological analysis was carried out on regenerated nerve fibers. In vitro investigation showed the formation of typical neuroglial cells after differentiation, which were positively stained for the typical specific neuroglial markers such as the GFAP, the GAP-43 and NeuN.
NMR showed clear evidence that HMSCs expansion is glycolysis-dependent but their differentiation requires the switch of the metabolic profile to oxidative metabolism. In vivo studies showed enhanced recovery of motor and sensory function in animals treated with transplanted undifferentiated and differentiated HMSCs that was accompanied by an increase in myelin sheath. Taken together, HMSC from the umbilical cord Wharton jelly might be useful for improving the clinical outcome after peripheral nerve lesion.
► Axonotmesis causes axonal interruption and induces functional loss. ► Wharton's jelly (WJ) is a non controversial source of MSCs. ► MSCs improve nerve regeneration and can differentiate into neuroglial-like cells. ► MSCs from WJ enhance the recovery of sensory/motor function. ► MSCs from WJ increase the myelin sheath of the regenerated fibers.
The dorsoventral axis of the
Drosophila embryo is patterned by a gradient of bone morphogenetic protein (BMP) ligands. In a process requiring at least three additional extracellular proteins, a broad ...domain of weak signaling forms and then abruptly sharpens into a narrow dorsal midline peak. Using experimental and computational approaches, we investigate how the interactions of a multiprotein network create the unusual shape and dynamics of formation of this gradient. Starting from observations suggesting that receptor-mediated BMP degradation is an important driving force in gradient dynamics, we develop a general model that is capable of capturing both subtle aspects of gradient behavior and a level of robustness that agrees with in vivo results.
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► Natural based polymers are processed by a variety of different supercritical fluid technologies. ► 3D architectures to serve as scaffolds for tissue engineering and regenerative ...medicine are presented. ► Controlled release systems were prepared for delivery of growth factors which induce stem cell differentiation. ► Examples of scaffold processing, preparation of delivery systems, polymer cross-linking reactions and matrices drying are given.
One of the major scientific challenges that tissue engineering and regenerative medicine (TERM) faces to move from benchtop to bedside regards biomaterials development, despite the latest advances in polymer processing technologies.
A variety of scaffolds processing techniques have been developed and include solvent casting and particles leaching, compression molding and particle leaching, thermally induced phase separation, rapid prototyping, among others. Supercritical fluids appear as an interesting alternative to the conventional methods for processing biopolymers as they do not require the use of large amounts of organic solvents and the processes can be conducted at mild temperatures. However, this processing technique has only recently started to receive more attention from researchers. Different processing methods based on the use of supercritical carbon dioxide have been proposed for the creation of novel architectures based on natural and synthetic polymers and these will be unleashed in this paper.
The design and evaluation of the imaging system Clear-PEM for positron emission mammography, under development by the PEM Consortium within the framework of the Crystal Clear Collaboration at CERN, ...is presented. The proposed apparatus is based on fast, segmented, high atomic number radiation sensors with depth-of-interaction measurement capabilities, and state-of-the-art data acquisition techniques. The camera consists of two compact and planar detector heads with dimensions 16.5/spl times/14.5 cm/sup 2/ for breast and axilla imaging. Low-noise integrated electronics provide signal amplification and analog multiplexing based on a new data-driven architecture. The coincidence trigger and data acquisition architecture makes extensive use of pipeline processing structures and multi-event memories for high efficiency up to a data acquisition rate of one million events/s. Experimental validation of the detection techniques, namely the basic properties of the radiation sensors and the ability to measure the depth-of-interaction of the incoming photons, are presented. System performance in terms of detection sensitivity, count-rates and reconstructed image spatial resolution were also evaluated by means of a detailed Monte Carlo simulation and an iterative image reconstruction algorithm.
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