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Stereolithography Cure Process Modeling Using Acrylate Resin
In this paper, a complex stereolithography (SL) cure process model is presented that
incorporates transient thermal and chemical effects which influence final part shape and
properties. The model incorporates photopolymerization, mass diffusion, and heat transfer.
Material properties are characterized and a comprehensive kinetic model parameterized for a
model compound system. SL process simulations are performed using finite element methods
with the software package FEMLAB, and validated by the capability of predicting the fabricated
part dimensions. A degree of cure (DOC) threshold model is proposed which can predict the cure
line size within 15% error, comparing with 30% prediction error by the exposure threshold
model currently used in SL. Furthermore, through the sensitivity analysis conducted by the
process model presented here, the sensitive parameters are identified and the SL bath
temperature, photointiator absorptivity and concentration are found to be the most sensitive
factors that affect the SL fabrication results. The sensitive variables will be the focus of further
research meant to improve SL process speed and resolution.Mechanical Engineerin
A self-powered pumping system for in situ extraction of particulate and dissolved materials from large volumes of seawater
A pumping system has been developed for the in situ extraction of particles and of dissolved constituents from large volumes of seawater. The assembly consists of a battery-powered submersible pump, filters, and chemisorptive
cartridges; it is entirely self-contained and has been used successfully
on ship's hydrographic wire to depths as great as 5800 m. The pump is
designed to operate at a maximum pressure drop of 66 cm of Hg; flow rates
have varied from 1.3 to 5.1 liters/min. We have sampled volumes as large as
758 liters, and the measured battery drain suggests that volumes several
times this could be pumped at any depth. The system is being used to study
a variety of artificial radionuclides, but modifications of the filter or
chemisorbent units would make it useful in many other geochemical
applications.Prepared for the U.S. Department of Energy under Contracts
DE-AC02-76EV03563 and DE-AC02-81EV10694 and through Sandia Laboratories under Contracts 13-2562 and 16/3112
Active Stat3 is required for survival of human squamous cell carcinoma cells in serum-free conditions
BACKGROUND: Squamous cell carcinoma (SCC) of the skin is the most aggressive form of non-melanoma skin cancer (NMSC), and is the single most commonly diagnosed cancer in the U.S., with over one million new cases reported each year. Recent studies have revealed an oncogenic role of activated signal transducer and activator of transcription 3 (Stat3) in many human tumors, especially in those of epithelial origin, including skin SCC. Stat3 is a mediator of numerous growth factor and cytokine signaling pathways, all of which activate it through phosphorylation of tyrosine 705. RESULTS: To further address the role of Stat3 in skin SCC tumorigenesis, we have analyzed a panel of human skin-derived cell lines ranging from normal human epidermal keratinocytes (NHEK), to non-tumorigenic transformed skin cells (HaCaT), to highly tumorigenic cells (SRB1-m7 and SRB12-p9) and observed a positive correlation between Stat3 phosphorylation and SCC malignancy. We next determined the role of Stat3 activity in cell proliferation and viability under serum-free culture conditions. This was accomplished by suppressing Stat3 activity in the SRB12-p9 cells through stable expression of a dominant negative acting form of Stat3β, which contains a tyrosine 705 to phenylalanine mutation (S3DN). The S3DN cells behaved similar to parental SRB12-p9 cells when cultured in optimal growth conditions, in the presence of 10% fetal calf serum. However, unlike the SRB12-p9 cells, S3DN cells underwent apoptotic cell death when cultured in serum-free medium (SFM). This was evidenced by multiple criteria, including accumulation of sub-G1 particles, induced PARP cleavage, and acquisition of the characteristic morphological changes associated with apoptosis. CONCLUSION: This study provides direct evidence for a role for Stat3 in maintaining cell survival in the conditions of exogenous growth factor deprivation produced by culture in SFM. We also propose that delivery of the S3DN gene or protein to tumor cells could induce apoptosis and/or sensitize those cells to the apoptotic effects of cancer therapeutic agents, raising the possibility of using S3DN as an adjunct for treatment of skin SCC
HGF/c-met/Stat3 signaling during skin tumor cell invasion: indications for a positive feedback loop
<p>Abstract</p> <p>Background</p> <p>Stat3 is a cytokine- and growth factor-inducible transcription factor that regulates cell motility, migration, and invasion under normal and pathological situations, making it a promising target for cancer therapeutics. The hepatocyte growth factor (HGF)/c-met receptor tyrosine kinase signaling pathway is responsible for stimulation of cell motility and invasion, and Stat3 is responsible for at least part of the c-met signal.</p> <p>Methods</p> <p>We have stably transfected a human squamous cell carcinoma (SCC) cell line (SRB12-p9) to force the expression of a dominant negative form of Stat3 (S3DN), which we have previously shown to suppress Stat3 activity. The <it>in vitro </it>and <it>in vivo </it>malignant behavior of the S3DN cells was compared to parental and vector transfected controls.</p> <p>Results</p> <p>Suppression of Stat3 activity impaired the ability of the S3DN cells to scatter upon stimulation with HGF (c-met ligand), enhanced their adhesion, and diminished their capacity to invade <it>in vitro </it>and <it>in vivo</it>. Surprisingly, S3DN cells also showed suppressed HGF-induced activation of c-met, and had nearly undetectable basal c-met activity, as revealed by a phospho-specific c-met antibody. In addition, we showed that there is a strong membrane specific localization of phospho-Stat3 in the wild type (WT) and vector transfected control (NEO4) SRB12-p9 cells, which is lost in the S3DN cells. Finally, co-immunoprecipitation experiments revealed that S3DN interfered with Stat3/c-met interaction.</p> <p>Conclusion</p> <p>These studies are the first confirm that interference with the HGF/c-met/Stat3 signaling pathway can block tumor cell invasion in an <it>in vivo </it>model. We also provide novel evidence for a possible positive feedback loop whereby Stat3 can activate c-met, and we correlate membrane localization of phospho-Stat3 with invasion <it>in vivo</it>.</p
Seroprevalence of Zika virus in wild African green monkeys and baboons
ABSTRACT Zika virus (ZIKV) has recently spread through the Americas and has been associated with a range of health effects, including birth defects in children born to women infected during pregnancy. Although the natural reservoir of ZIKV remains poorly defined, the virus was first identified in a captive “sentinel” macaque monkey in Africa in 1947. However, the virus has not been reported in humans or nonhuman primates (NHPs) in Africa outside Gabon in over a decade. Here, we examine ZIKV infection in 239 wild baboons and African green monkeys from South Africa, the Gambia, Tanzania, and Zambia using combinations of unbiased deep sequencing, quantitative reverse transcription-PCR (qRT-PCR), and an antibody capture assay that we optimized using serum collected from captive macaque monkeys exposed to ZIKV, dengue virus, and yellow fever virus. While we did not find evidence of active ZIKV infection in wild NHPs in Africa, we found variable ZIKV seropositivity of up to 16% in some of the NHP populations sampled. We anticipate that these results and the methodology described within will help in continued efforts to determine the prevalence, natural reservoir, and transmission dynamics of ZIKV in Africa and elsewhere. IMPORTANCE Zika virus (ZIKV) is a mosquito-borne virus originally discovered in a captive monkey living in the Zika Forest of Uganda, Africa, in 1947. Recently, an outbreak in South America has shown that ZIKV infection can cause myriad health effects, including birth defects in the children of women infected during pregnancy. Here, we sought to investigate ZIKV infection in wild African primates to better understand its emergence and spread, looking for evidence of active or prior infection. Our results suggest that up to 16% of some populations of nonhuman primate were, at some point, exposed to ZIKV. We anticipate that this study will be useful for future studies that examine the spread of infections from wild animals to humans in general and those studying ZIKV in primates in particular. Podcast: A podcast concerning this article is available
Ariel - Volume 4 Number 3
Editors
David A. Jacoby
Eugenia Miller
Tom Williams
Associate Editors
Paul Bialas
Terry Burt
Michael Leo
Gail Tenikat
Editor Emeritus and Business Manager
Richard J. Bonnano
Movie Editor
Robert Breckenridge
Staff
Richard Blutstein
Mary F. Buechler
Steve Glinks
Len Grasman
Alice M. Johnson
J.D. Kanofsky
Tom Lehman
Dave Mayer
Bernie Odd
Profiling lung adenocarcinoma by liquid biopsy: can one size fit all?
BACKGROUND: Cancer is first and foremost a disease of the genome. Specific genetic signatures within a tumour are prognostic of disease outcome, reflect subclonal architecture and intratumour heterogeneity, inform treatment choices and predict the emergence of resistance to targeted therapies. Minimally invasive liquid biopsies can give temporal resolution to a tumour's genetic profile and allow the monitoring of treatment response through levels of circulating tumour DNA (ctDNA). However, the detection of ctDNA in repeated liquid biopsies is currently limited by economic and time constraints associated with targeted sequencing. METHODS: Here we bioinformatically profile the mutational and copy number spectrum of The Cancer Genome Network's lung adenocarcinoma dataset to uncover recurrently mutated genomic loci. RESULTS: We build a panel of 400 hotspot mutations and show that the coverage extends to more than 80% of the dataset at a median depth of 8 mutations per patient. Additionally, we uncover several novel single-nucleotide variants present in more than 5% of patients, often in genes not commonly associated with lung adenocarcinoma. CONCLUSION: With further optimisation, this hotspot panel could allow molecular diagnostics laboratories to build curated primer banks for 'off-the-shelf' monitoring of ctDNA by droplet-based digital PCR or similar techniques, in a time- and cost-effective manner
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