1,209 research outputs found
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SLS Processing Studies of Nylon 11 Nanocomposites
Selective Laser Sintering (SLS) is widely used for rapid prototyping/manufacturing of
nylon 11 and nylon 12 parts. This processing technique has not been explored for
nylon nanocomposites. This study investigates the technicalities of processing nylon
11-clay and nylon-carbon nanofiber nanocomposites with SLS. Microstructural
analyses of the SLS powders and parts were conducted under SEM. Results suggest
that SLS processing is possible with the new nylon 11 nanocomposites. Yet the SLS
parts built have inferior properties relative to those of injection molding, suggesting
that more fine tuning for the processing is required.Mechanical Engineerin
Etanercept in the treatment of plaque psoriasis
Etanercept is approved for the treatment of moderate to severe plaque psoriasis at a dose of 50 mg twice weekly for 3 months followed by a maintenance dosage of 50 mg weekly thereafter. Clinical studies have shown excellent efficacy, favorable benefit to side-effects ratio, and safe long-term usage. Extensive information on safety is available as etanercept has been used for many years for other indications such as rheumatoid arthritis and psoriatic arthritis and is the first of the tumor necrosis factor antagonists to gain approval in psoriasis
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Mammalian EAK-7 activates alternative mTOR signaling to regulate cell proliferation and migration.
Nematode EAK-7 (enhancer-of-akt-1-7) regulates dauer formation and controls life span; however, the function of the human ortholog mammalian EAK-7 (mEAK-7) is unknown. We report that mEAK-7 activates an alternative mechanistic/mammalian target of rapamycin (mTOR) signaling pathway in human cells, in which mEAK-7 interacts with mTOR at the lysosome to facilitate S6K2 activation and 4E-BP1 repression. Despite interacting with mTOR and mammalian lethal with SEC13 protein 8 (mLST8), mEAK-7 does not interact with other mTOR complex 1 (mTORC1) or mTOR complex 2 (mTORC2) components; however, it is essential for mTOR signaling at the lysosome. This phenomenon is distinguished by S6 and 4E-BP1 activity in response to nutrient stimulation. Conventional S6K1 phosphorylation is uncoupled from S6 phosphorylation in response to mEAK-7 knockdown. mEAK-7 recruits mTOR to the lysosome, a crucial compartment for mTOR activation. Loss of mEAK-7 results in a marked decrease in lysosomal localization of mTOR, whereas overexpression of mEAK-7 results in enhanced lysosomal localization of mTOR. Deletion of the carboxyl terminus of mEAK-7 significantly decreases mTOR interaction. mEAK-7 knockdown decreases cell proliferation and migration, whereas overexpression of mEAK-7 enhances these cellular effects. Constitutively activated S6K rescues mTOR signaling in mEAK-7-knocked down cells. Thus, mEAK-7 activates an alternative mTOR signaling pathway through S6K2 and 4E-BP1 to regulate cell proliferation and migration
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mEAK-7 Forms an Alternative mTOR Complex with DNA-PKcs in Human Cancer.
MTOR associated protein, eak-7 homolog (mEAK-7), activates mechanistic target of rapamycin (mTOR) signaling in human cells through an alternative mTOR complex to regulate S6K2 and 4E-BP1. However, the role of mEAK-7 in human cancer has not yet been identified. We demonstrate that mEAK-7 and mTOR signaling are strongly elevated in tumor and metastatic lymph nodes of patients with non-small-cell lung carcinoma compared with those of patients with normal lung or lymph tissue. Cancer stem cells, CD44+/CD90+ cells, yield elevated mEAK-7 and activated mTOR signaling. mEAK-7 is required for clonogenic potential and spheroid formation. mEAK-7 associates with DNA-dependent protein kinase catalytic subunit isoform 1 (DNA-PKcs), and this interaction is increased in response to X-ray irradiation to regulate S6K2 signaling. DNA-PKcs pharmacologic inhibition or genetic knockout reduced S6K2, mEAK-7, and mTOR binding with DNA-PKcs, resulting in loss of S6K2 activity and mTOR signaling. Therefore, mEAK-7 forms an alternative mTOR complex with DNA-PKcs to regulate S6K2 in human cancer cells
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Innovative Selective Laser Sintering Rapid Manufacturing using Nanotechnology
The objective of this research is to develop an improved nylon 11 (polyamide 11) polymer
with enhanced flame retardancy, thermal, and mechanical properties for selective laser sintering
(SLS) rapid manufacturing (RM). A nanophase was introduced into nylon 11 via twin screw
extrusion to provide improved material properties of the polymer blends. Atofina (now known
as Arkema) RILSAN® nylon 11 injection molding polymer pellets was used with three types of
nanoparticles: chemically modified montmorillonite (MMT) organoclays, nanosilica, and carbon
nanofibers (CNF) to create nylon 11 nanocomposites. Wide angle X-ray diffraction (WAXD)
and transmission electron microscopy (TEM) were used to determine the degree of dispersion.
Fifteen nylon 11 nanocomposites and control nylon 11 were fabricated by injection molding.
Flammability properties (using a cone calorimeter with a radiant flux of 50 kW/m2
) and
mechanical properties such as tensile strength and modulus, flexural modulus, elongation at
break were determined for the nylon 11 nanocomposites and compared with the baseline nylon
11. Based on flammability and mechanical material performance, five polymers including four
nylon 11 nanocomposites and a control nylon 11 were cryogenically ground into fine powders
for SLS RM. SLS specimens were fabricated for flammability, mechanical, and thermal
properties characterization. Nylon 11-CNF nanocomposites exhibited the best overall properties
for this study.Mechanical Engineerin
Functional rescue of dystrophin deficiency in mice caused by frameshift mutations using Campylobacter jejuni Cas9
Duchenne muscular dystrophy (DMD) is a fatal, X-linked muscle wasting disease caused by mutations in the DMD gene. In 51% of DMD cases, a reading frame is disrupted because of deletion of several exons. Here, we show that CjCas9 derived from Campylobacter jejuni can be
used as a gene editing tool to correct an out-of-frame Dmd exon in Dmd knockout mice. Herein, we used Cas9 derived from S. pyogenes to generate Dmd knockout (KO) mice with a frameshift mutation in Dmd gene. Then, we expressed CjCas9, its single-guide RNA, and the eGFP gene
in the tibialis anterior muscle of the Dmd KO mice using an all-in-one adeno-associated virus (AAV) vector. CjCas9 cleaved the target site in the Dmd gene efficiently in vivo and induced small insertions or deletions at the target site. This treatment resulted in conversion of the
disrupted Dmd reading frame from out-of-frame to in-frame, leading to the expression of dystrophin in the sarcolemma. Importantly, muscle strength was enhanced in the CjCas9-treated muscles, without off-target mutations, indicating high efficiency and specificity of CjCas9. This work suggests that in vivo DMD frame correction, mediated by CjCas9 has great potential for the treatment of DMD and other neuromuscular diseases
A biomimetic pancreatic cancer on-chip reveals endothelial ablation via ALK7 signaling
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive, lethal malignancy that invades adjacent vasculatures and spreads to distant sites before clinical detection. Although invasion into the peripancreatic vasculature is one of the hallmarks of PDAC, paradoxically, PDAC tumors also exhibit hypovascularity. How PDAC tumors become hypovascular is poorly understood. We describe an organotypic PDAC-on-a-chip culture model that emulates vascular invasion and tumor-blood vessel interactions to better understand PDAC-vascular interactions. The model features a 3D matrix containing juxtaposed PDAC and perfusable endothelial lumens. PDAC cells invaded through intervening matrix, into vessel lumen, and ablated the endothelial cells, leaving behind tumor-filled luminal structures. Endothelial ablation was also observed in in vivo PDAC models. We also identified the activin-ALK7 pathway as a mediator of endothelial ablation by PDAC. This tumor-on-a-chip model provides an important in vitro platform for investigating the process of PDAC-driven endothelial ablation and may provide a mechanism for tumor hypovascularity.R01 EB000262 - NIBIB NIH HHS; TL1 TR001410 - NCATS NIH HHS; UC4 DK104196 - NIDDK NIH HHS; UH3 EB017103 - NIBIB NIH HHSPublished versio
Direct measurement of mechanical vibrations of the 4-rod RFQ at the HLI
In this paper, we present a new haptic interface, called active skin , which is configured with a tactile sensor and a tactile stimulator in single haptic cell, and multiple haptic cells are embedded in a dielectric elastomer. The active skin generates a wide variety of haptic feel in response to the touch by synchronizing the sensor and the stimulator. In this paper, the design of the haptic cell is derived via iterative analysis and design procedures. A fabrication method dedicated to the proposed device is investigated and a controller to drive multiple haptic cells is developed. In addition, several experiments are performed to evaluate the performance of the active skin
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