1,216 research outputs found

    Serration phenomena occurring during tensile tests of three high-manganese TWinning Induced Plasticity (TWIP) steels

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    In this study, the serration phenomena of two high-Mn TWIP steels and an Al-added TWIP steel were examined by tensile tests, and were explained by the microstructural evolution including formation of localized Portevin-Le Chatelier deformation bands and twins. In stress-strain curves of the high-Mn steels, serrations started in a fine and short shape, and their height and periodic interval increased with increasing strain, whereas the Al-added steel did not show any serrations. According to digital images of strain rate and strain obtained from a vision strain gage system, deformation bands were initially formed at the upper region of the gage section, and moved downward along the tensile loading direction. The time when the band formation started was matched with the time when one serration occurred in the stress-time curve. This serration behavior was generally explained by dynamic strain aging, which was closely related with the formation of deformation bands. (C) The Minerals, Metals & Materials Society and ASM International 2013ope

    New synchronization method for <i>Plasmodium falciparum</i>

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    &lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

    Evaluation of two high-throughput proteomic technologies for plasma biomarker discovery in immunotherapy-treated melanoma patients

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    Background: Selective kinase and immune checkpoint inhibitors, and their combinations, have significantly improved the survival of patients with advanced metastatic melanoma. Not all patients will respond to treatment however, and some patients will present with significant toxicities. Hence, the identification of biomarkers is critical for the selection and management of patients receiving treatment. Biomarker discovery often involves proteomic techniques that simultaneously profile multiple proteins but few studies have compared these platforms. Methods: In this study, we used the multiplex bead-based Eve Technologies Discovery assay and the aptamer-based SomaLogic SOMAscan assay to identify circulating proteins predictive of response to immunotherapy in melanoma patients treated with combination immune checkpoint inhibitors. Expression of four plasma proteins were further validated using the bead-based Millipore Milliplex assay. Results: Both the Discovery and the SOMAscan assays detected circulating plasma proteins in immunotherapy-treated melanoma patients. However, these widely used assays showed limited correlation in relative protein quantification, due to differences in specificity and the dynamic range of protein detection. Protein data derived from the Discovery and Milliplex bead-based assays were highly correlated. Conclusions: Our study highlights significant limitations imposed by inconsistent sensitivity and specificity due to differences in the detection antibodies or aptamers of these widespread biomarker discovery approaches. Our findings emphasize the need to improve these technologies for the accurate identification of biomarkers

    Automated measurement of infant and mother Duchenne facial expressions in the Face-to-Face/Still-Face

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    Although still-face effects are well-studied, little is known about the degree to which the Face-to-Face/Still-Face (FFSF) is associated with the production of intense affective displays. Duchenne smiling expresses more intense positive affect than non-Duchenne smiling, while Duchenne cry-faces express more intense negative affect than non-Duchenne cry-faces. Forty 4-month-old infants and their mothers completed the FFSF, and key affect-indexing facial Action Units (AUs) were coded by expert Facial Action Coding System coders for the first 30 s of each FFSF episode. Computer vision software, automated facial affect recognition (AFAR), identified AUs for the entire 2-min episodes. Expert coding and AFAR produced similar infant and mother Duchenne and non-Duchenne FFSF effects, highlighting the convergent validity of automated measurement. Substantive AFAR analyses indicated that both infant Duchenne and non-Duchenne smiling declined from the FF to the SF, but only Duchenne smiling increased from the SF to the RE. In similar fashion, the magnitude of mother Duchenne smiling changes over the FFSF were 2–4 times greater than non-Duchenne smiling changes. Duchenne expressions appear to be a sensitive index of intense infant and mother affective valence that are accessible to automated measurement and may be a target for future FFSF research

    Measurement Reliability for Acupoint Activity Determined with the Prognos Ohmmeter

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    The concepts of meridians and acupoints are critical to traditional Chinese medicine but are met with skepticism in Western medicine. Empirical validation of these concepts is in its beginning stages and still hampered by problems with measurement. A promising avenue and foundation for validity testing is the demonstration that acupoint activity can be reliably measured via determination of electrical resistance at well-defined body surface points. In this article, efforts are described to maximize measurement reliability; we tested a variety of protocols to determine which method of data aggregation is associated with maximal reliability. Twenty-one healthy individuals were subjected to 5 repeated measurement cycles to test the predicted increase in reliability with increasing number of aggregated measurements. Reliability, defined as internal consistency, was indeed highest for 5 measurements (mean alpha = .88). Even the aggregate of only three measures was quite reliable (alpha = .84). Reliability for measuring acupoints on the left side of the body was roughly .05 higher than on the right side. Consistent with previous literature, we conclude that with repeated measures the reliability of electrical resistance measurements at acupoints is high and that a strong foundation for validation research is now laid

    Enhanced anti-tumor effects of combined MDR1 RNA interference and human sodium/iodide symporter (NIS) radioiodine gene therapy using an adenoviral system in a colon cancer model

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    Using an adenoviral system as a delivery mediator of therapeutic gene, we investigated the therapeutic effects of the use of combined MDR1 shRNA and human NIS (hNIS) radioiodine gene therapy in a mouse colon xenograft model. In vitro uptake of Tc-99m sestamibi was increased approximately two-fold in cells infected with an adenovirus vector that expressed MDR1 shRNA (Ad-shMDR1) and I-125 uptake was 25-fold higher in cells infected with an adenovirus vector that expressed human NIS (Ad-hNIS) as compared with control cells. As compared with doxorubicin or I-131 treatment alone, the combination of doxorubicin and I-131 resulted in enhanced cytotoxicity for both Ad-shMDR1- and Ad-hNIS-infected cells, but not for control cells. In vivo uptake of Tc-99m sestamibi and Tc-99m pertechnetate was twofold and 10-fold higher for Ad-shMDR1 and Ad-hNIS-infected tumors as compared with tumors infected with a control adenovirus construct that expressed β-galactrosidase (Ad-LacZ), respectively. In mice treated with either doxorubicin or I-131 alone, there was a slight delay in tumor growth as compared to mice treated with Ad-LacZ. However, combination therapy with doxorubicin and I-131 induced further significant inhibition of tumor growth as compared with mice treated with Ad-LacZ. We have shown successful therapeutic efficacy of combined MDR shRNA and hNIS radioiodine gene therapy using an adenoviral vector system in a mouse colon cancer model. Adenovirus-mediated cancer gene therapy using MDR1 shRNA and hNIS would be a useful tool for the treatment of cancer cells expressing multi-drug resistant genes

    Phosphoenolpyruvate carboxylase dentified as a key enzyme in erythrocytic Plasmodium falciparum carbon metabolism

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    Phospoenolpyruvate carboxylase (PEPC) is absent from humans but encoded in thePlasmodium falciparum genome, suggesting that PEPC has a parasite-specific function. To investigate its importance in P. falciparum, we generated a pepc null mutant (D10Δpepc), which was only achievable when malate, a reduction product of oxaloacetate, was added to the growth medium. D10Δpepc had a severe growth defect in vitro, which was partially reversed by addition of malate or fumarate, suggesting that pepc may be essential in vivo. Targeted metabolomics using 13C-U-D-glucose and 13C-bicarbonate showed that the conversion of glycolytically-derived PEP into malate, fumarate, aspartate and citrate was abolished in D10Δpepc and that pentose phosphate pathway metabolites and glycerol 3-phosphate were present at increased levels. In contrast, metabolism of the carbon skeleton of 13C,15N-U-glutamine was similar in both parasite lines, although the flux was lower in D10Δpepc; it also confirmed the operation of a complete forward TCA cycle in the wild type parasite. Overall, these data confirm the CO2 fixing activity of PEPC and suggest that it provides metabolites essential for TCA cycle anaplerosis and the maintenance of cytosolic and mitochondrial redox balance. Moreover, these findings imply that PEPC may be an exploitable target for future drug discovery

    Efficacy of Lactic Acid Bacteria (LAB) supplement in management of constipation among nursing home residents

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    <p>Abstract</p> <p>Background</p> <p>Constipation is a significant problem in the elderly, specifically nursing home and/or extended-care facility residents are reported to suffer from constipation. Lactic acid bacteria (LAB) are beneficial probiotic organisms that contribute to improved nutrition, microbial balance, and immuno-enhancement of the intestinal tract, as well as diarrhea and constipation effect. The objective of this study was to investigate the efficacy of this LAB supplement in the management of nursing home residents.</p> <p>Methods</p> <p>Nineteen subjects (8M, 11F; mean age 77.1 ± 10.1) suffering with chronic constipation were assigned to receive LAB (3.0 × 10<sup>11 </sup>CFU/g) twice (to be taken 30 minutes after breakfast and dinner) a day for 2 weeks in November 2008. Subjects draw up a questionnaire on defecation habits (frequency of defecation, amount and state of stool), and we collected fecal samples from the subjects both before entering and after ending the trial, to investigate LAB levels and inhibition of harmful enzyme activities. Results were tested with SAS and Student's t-test.</p> <p>Results</p> <p>Analysis of questionnaire showed that there was an increase in the frequency of defecation and amount of stool excreted in defecation habit after LAB treatment, but there were no significant changes. And it also affects the intestinal environment, through significantly increase (<it>p </it>< 0.05) fecal LAB levels. In addition, tryptophanase and urease among harmful enzyme activities of intestinal microflora were significantly decreased (<it>p </it>< 0.05) after LAB treatment.</p> <p>Conclusion</p> <p>LAB, when added to the standard treatment regimen for nursing home residents with chronic constipation, increased defecation habit such as frequency of defecation, amount and state of stool. So, it may be used as functional probiotics to improve human health by helping to prevent constipation.</p
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