MUC1 enhances tumor progression and contributes towards immunosuppression in a mouse model of spontaneous pancreatic adenocarcinoma

PubMed Central

Tinder, Teresa L.; Subramani, Durai B.; Basu, Gargi D.; Bradley, Judy M.; Schettini, Jorge; Million, Arefayene; Skaar, Todd

2008-01-01

MUC1, a membrane tethered mucin glycoprotein, is overexpressed and aberrantly glycosylated in >80% of human ductal pancreatic adenocarcinoma. However, the role of MUC1 in pancreatic cancer has been elusive, partly due to the lack of an appropriate model. We report the characterization of a novel mouse model that expresses human MUC1 as a self molecule (PDA.MUC1 mice). Pancreatic tumors arise in an appropriate MUC1-tolerant background within an immune competent host. Significant enhancement in the development of pancreatic intraepithelial pre-neoplastic lesions (PanINs) and progression to adenocarcinoma is observed in PDA.MUC1 mice, possibly due to increased proliferation. Tumors from PDA.MUC1 mice express higher levels of cyclooxygenase-2 and indoleamine 2,3, dioxygenase compared to PDA mice lacking MUC1, especially during early stages of tumor development. The increased pro-inflammatory milieu correlates with an increased percentage of regulatory T cells and myeloid suppressor cells in the pancreatic tumor and tumor draining lymph nodes. Data shows that during pancreatic cancer progression, MUC1-mediated mechanisms enhance the onset and progression of the disease which in turn regulate the immune responses. Thus, the mouse model is ideally-suited for testing novel chemopreventive and therapeutic strategies against pancreatic cancer. PMID:18713982

Plants and their bioactive compounds with the potential to enhance mechanisms of inherited cardiac regeneration.

PubMed

Zhou, Zhen; Li, Dianbin; Zhou, Hua; Lin, Xiaoli; Li, Censing; Tang, Mingfeng; Feng, Zhou; Li, Ming

2015-06-01

This article reviews the current progress and research indications in the application of natural plant compounds with the potential for the treatment of cardiovascular diseases. Our understanding of how to apply natural plant compounds to enhance mechanisms of inherited cardiac regeneration, which is physiologically pertinent to myocyte turnover or minor cardiac repair, for substantial cardiac regeneration to repair pathological heart injuries is discussed. Although significant progress has been made in the application of natural plant compounds for therapy of heart diseases, the understanding or the application of these compounds specifically for enhancing mechanisms of inherited cardiac regeneration for the treatment of cardiovascular diseases is little. Recent recognition of some natural plant compounds that can repair damaged myocardial tissues through enhancing mechanisms of inherited cardiac regeneration has offered an alternative for clinical translation. Application of natural plant compounds, which show the activity of manipulating gene expressions in such a way to enhance mechanisms of inherited cardiac regeneration for cardiac repair, may provide a promising strategy for the reconstruction of damaged cardiac tissues due to cardiovascular diseases. Georg Thieme Verlag KG Stuttgart · New York.

Fundamental and progress of Bi2Te3-based thermoelectric materials

NASA Astrophysics Data System (ADS)

Hong, Min; Chen, Zhi-Gang; Zou, Jin

2018-04-01

Thermoelectric materials, enabling the directing conversion between heat and electricity, are one of the promising candidates for overcoming environmental pollution and the upcoming energy shortage caused by the over-consumption of fossil fuels. Bi2Te3-based alloys are the classical thermoelectric materials working near room temperature. Due to the intensive theoretical investigations and experimental demonstrations, significant progress has been achieved to enhance the thermoelectric performance of Bi2Te3-based thermoelectric materials. In this review, we first explored the fundamentals of thermoelectric effect and derived the equations for thermoelectric properties. On this basis, we studied the effect of material parameters on thermoelectric properties. Then, we analyzed the features of Bi2Te3-based thermoelectric materials, including the lattice defects, anisotropic behavior and the strong bipolar conduction at relatively high temperature. Then we accordingly summarized the strategies for enhancing the thermoelectric performance, including point defect engineering, texture alignment, and band gap enlargement. Moreover, we highlighted the progress in decreasing thermal conductivity using nanostructures fabricated by solution grown method, ball milling, and melt spinning. Lastly, we employed modeling analysis to uncover the principles of anisotropy behavior and the achieved enhancement in Bi2Te3, which will enlighten the enhancement of thermoelectric performance in broader materials.

Quantitative T2 mapping of recurrent glioblastoma under bevacizumab improves monitoring for non-enhancing tumor progression and predicts overall survival

PubMed Central

Hattingen, Elke; Jurcoane, Alina; Daneshvar, Keivan; Pilatus, Ulrich; Mittelbronn, Michel; Steinbach, Joachim P.; Bähr, Oliver

2013-01-01

Background Anti-angiogenic treatment in recurrent glioblastoma patients suppresses contrast enhancement and reduces vasogenic edema while non-enhancing tumor progression is common. Thus, the importance of T2-weighted imaging is increasing. We therefore quantified T2 relaxation times, which are the basis for the image contrast on T2-weighted images. Methods Conventional and quantitative MRI procedures were performed on 18 patients with recurrent glioblastoma before treatment with bevacizumab and every 8 weeks thereafter until further tumor progression. We segmented the tumor on conventional MRI into 3 subvolumes: enhancing tumor, non-enhancing tumor, and edema. Using coregistered quantitative maps, we followed changes in T2 relaxation time in each subvolume. Moreover, we generated differential T2 maps by a voxelwise subtraction using the first T2 map under bevacizumab as reference. Results Visually segmented areas of tumor and edema did not differ in T2 relaxation times. Non-enhancing tumor volume did not decrease after commencement of bevacizumab treatment but strikingly increased at progression. Differential T2 maps clearly showed non-enhancing tumor progression in previously normal brain. T2 relaxation times decreased under bevacizumab without re-increasing at tumor progression. A decrease of <26 ms in the enhancing tumor following exposure to bevacizumab was associated with longer overall survival. Conclusions Combining quantitative MRI and tumor segmentation improves monitoring of glioblastoma patients under bevacizumab. The degree of change in T2 relaxation time under bevacizumab may be an early response parameter predictive of overall survival. The sustained decrease in T2 relaxation times toward values of healthy tissue masks progressive tumor on conventional T2-weighted images. Therefore, quantitative T2 relaxation times may detect non-enhancing progression better than conventional T2-weighted imaging. PMID:23925453

Tumor-derived exosomes promote tumor self-seeding in hepatocellular carcinoma by transferring miRNA-25-5p to enhance cell motility.

PubMed

Liu, Hao; Chen, Wei; Zhi, Xiao; Chen, En-Jiang; Wei, Tao; Zhang, Jian; Shen, Jian; Hu, Li-Qiang; Zhao, Bin; Feng, Xin-Hua; Bai, Xue-Li; Liang, Ting-Bo

2018-05-22

Tumor self-seeding occurs when circulating malignant cells reinfiltrate the original tumor. The process may breed more aggressive tumor cells, which may contribute to cancer progression. In this study, we observed tumor self-seeding in mouse xenograft models of hepatocellular carcinoma (HCC) for the first time. We confirmed that circulating tumor cell uptake of tumor-derived exosomes, which are increasingly recognized as key instigators of cancer progression by facilitating cell-cell communication, promoted tumor self-seeding by enhancing the invasive and migration capability of recipient HCC cells. Horizontal transfer of exosomal microRNA-25-5p to anoikis-resistant HCC cells significantly enhanced their migratory and invasive abilities, whereas inhibiting microRNA-25-5p alleviated these effects. Our experiments delineate an exosome-based novel pathway employed by functional microRNA from the original tumor cells that can influence the biological fate of circulating tumor cells.

N-acetyl-cysteine increases cellular dysfunction in progressive chronic kidney damage after acute kidney injury by dampening endogenous antioxidant responses.

PubMed

Small, David M; Sanchez, Washington Y; Roy, Sandrine F; Morais, Christudas; Brooks, Heddwen L; Coombes, Jeff S; Johnson, David W; Gobe, Glenda C

2018-05-01

Oxidative stress and mitochondrial dysfunction exacerbate acute kidney injury (AKI), but their role in any associated progress to chronic kidney disease (CKD) remains unclear. Antioxidant therapies often benefit AKI, but their benefits in CKD are controversial since clinical and preclinical investigations often conflict. Here we examined the influence of the antioxidant N-acetyl-cysteine (NAC) on oxidative stress and mitochondrial function during AKI (20-min bilateral renal ischemia plus reperfusion/IR) and progression to chronic kidney pathologies in mice. NAC (5% in diet) was given to mice 7 days prior and up to 21 days post-IR (21d-IR). NAC treatment resulted in the following: prevented proximal tubular epithelial cell apoptosis at early IR (40-min postischemia), yet enhanced interstitial cell proliferation at 21d-IR; increased transforming growth factor-β1 expression independent of IR time; and significantly dampened nuclear factor-like 2-initiated cytoprotective signaling at early IR. In the long term, NAC enhanced cellular metabolic impairment demonstrated by increased peroxisome proliferator activator-γ serine-112 phosphorylation at 21d-IR. Intravital multiphoton microscopy revealed increased endogenous fluorescence of nicotinamide adenine dinucleotide (NADH) in cortical tubular epithelial cells during ischemia, and at 21d-IR that was not attenuated with NAC. Fluorescence lifetime imaging microscopy demonstrated persistent metabolic impairment by increased free/bound NADH in the cortex at 21d-IR that was enhanced by NAC. Increased mitochondrial dysfunction in remnant tubular cells was demonstrated at 21d-IR by tetramethylrhodamine methyl ester fluorimetry. In summary, NAC enhanced progression to CKD following AKI not only by dampening endogenous cellular antioxidant responses at time of injury but also by enhancing persistent kidney mitochondrial and metabolic dysfunction.

Effects of age and gender on neural networks of motor response inhibition: from adolescence to mid-adulthood.

PubMed

Rubia, Katya; Lim, Lena; Ecker, Christine; Halari, Rozmin; Giampietro, Vincent; Simmons, Andrew; Brammer, Michael; Smith, Anna

2013-12-01

Functional inhibitory neural networks mature progressively with age. However, nothing is known about the impact of gender on their development. This study employed functional magnetic resonance imaging (fMRI) to investigate the effects of age, sex, and sex by age interactions on the brain activation of 63 healthy males and females, between 13 and 38 years, performing a Stop task. Increasing age was associated with progressively increased activation in typical response inhibition areas of right inferior and dorsolateral prefrontal and temporo-parietal regions. Females showed significantly enhanced activation in left inferior and superior frontal and striatal regions relative to males, while males showed increased activation relative to females in right inferior and superior parietal areas. Importantly, left frontal and striatal areas that showed increased activation in females, also showed significantly increased functional maturation in females relative to males, while the right inferior parietal activation that was increased in males showed significantly increased functional maturation relative to females. The findings demonstrate for the first time that sex-dimorphic activation patterns of enhanced left fronto-striatal activation in females and enhanced right parietal activation in males during motor inhibition appear to be the result of underlying gender differences in the functional maturation of these brain regions. © 2013. Published by Elsevier Inc. All rights reserved.

Histone deacetylase (HDAC)-1, -2, -4 and -6 expression in human pancreatic adenocarcinoma: associations with clinicopathological parameters, tumor proliferative capacity and patients' survival.

PubMed

Giaginis, Constantinos; Damaskos, Christos; Koutsounas, Ioannis; Zizi-Serbetzoglou, Adamantia; Tsoukalas, Nicolaos; Patsouris, Efstratios; Kouraklis, Gregorios; Theocharis, Stamatios

2015-10-26

Histone deacetylases (HDACs) have been associated with malignant tumor development and progression in humans. HDAC inhibitors (HDACIs) are currently being explored as anti-cancer agents in clinical trials. The present study aimed to evaluate the clinical significance of HDAC-1, -2, -4 and -6 protein expression in pancreatic adenocarcinoma. HDAC-1, -2, -4 and -6 protein expression was assessed immunohistochemically on 70 pancreatic adenocarcinoma tissue specimens and was statistically analyzed with clinicopathological characteristics and patients' survival. Enhanced HDAC-1 expression was significantly associated with increased tumor proliferative capacity (p = 0.0238) and borderline with the absence of lymph node metastases (p = 0.0632). Elevated HDAC-4 expression was significantly associated with the absence of organ metastases (p = 0.0453) and borderline with the absence of lymph node metastases (p = 0.0571) and tumor proliferative capacity (p = 0.0576). Enhanced HDAC-6 expression was significantly associated with earlier histopathological stage (p = 0.0115) and borderline with smaller tumor size (p = 0.0864). Pancreatic adenocarcinoma patients with enhanced HDAC-1 and -6 expression showed significantly longer survival times compared to those with low expression (p = 0.0022 and p = 0.0113, respectively), while a borderline association concerning HDAC-2 expression was noted (p = 0.0634). The present study suggested that HDACs may be implicated in pancreatic malignant disease progression, being considered of clinical utility with potential use as therapeutic targets.

Comparison between the Prebolus T1 Measurement and the Fixed T1 Value in Dynamic Contrast-Enhanced MR Imaging for the Differentiation of True Progression from Pseudoprogression in Glioblastoma Treated with Concurrent Radiation Therapy and Temozolomide Chemotherapy.

PubMed

Nam, J G; Kang, K M; Choi, S H; Lim, W H; Yoo, R-E; Kim, J-H; Yun, T J; Sohn, C-H

2017-12-01

Glioblastoma is the most common primary brain malignancy and differentiation of true progression from pseudoprogression is clinically important. Our purpose was to compare the diagnostic performance of dynamic contrast-enhanced pharmacokinetic parameters using the fixed T1 and measured T1 on differentiating true from pseudoprogression of glioblastoma after chemoradiation with temozolomide. This retrospective study included 37 patients with histopathologically confirmed glioblastoma with new enhancing lesions after temozolomide chemoradiation defined as true progression ( n = 15) or pseudoprogression ( n = 22). Dynamic contrast-enhanced pharmacokinetic parameters, including the volume transfer constant, the rate transfer constant, the blood plasma volume per unit volume, and the extravascular extracellular space per unit volume, were calculated by using both the fixed T1 of 1000 ms and measured T1 by using the multiple flip-angle method. Intra- and interobserver reproducibility was assessed by using the intraclass correlation coefficient. Dynamic contrast-enhanced pharmacokinetic parameters were compared between the 2 groups by using univariate and multivariate analysis. The diagnostic performance was evaluated by receiver operating characteristic analysis and leave-one-out cross validation. The intraclass correlation coefficients of all the parameters from both T1 values were fair to excellent (0.689-0.999). The volume transfer constant and rate transfer constant from the fixed T1 were significantly higher in patients with true progression ( P = .048 and .010, respectively). Multivariate analysis revealed that the rate transfer constant from the fixed T1 was the only independent variable (OR, 1.77 × 10 5 ) and showed substantial diagnostic power on receiver operating characteristic analysis (area under the curve, 0.752; P = .002). The sensitivity and specificity on leave-one-out cross validation were 73.3% (11/15) and 59.1% (13/20), respectively. The dynamic contrast-enhanced parameter of rate transfer constant from the fixed T1 acted as a preferable marker to differentiate true progression from pseudoprogression. © 2017 by American Journal of Neuroradiology.

Combining image-processing and image compression schemes

NASA Technical Reports Server (NTRS)

Greenspan, H.; Lee, M.-C.

1995-01-01

An investigation into the combining of image-processing schemes, specifically an image enhancement scheme, with existing compression schemes is discussed. Results are presented on the pyramid coding scheme, the subband coding scheme, and progressive transmission. Encouraging results are demonstrated for the combination of image enhancement and pyramid image coding schemes, especially at low bit rates. Adding the enhancement scheme to progressive image transmission allows enhanced visual perception at low resolutions. In addition, further progressing of the transmitted images, such as edge detection schemes, can gain from the added image resolution via the enhancement.

Baseline Fourier-Domain Optical Coherence Tomography Structural Risk Factors for Visual Field Progression in the Advanced Imaging for Glaucoma Study.

PubMed

Zhang, Xinbo; Dastiridou, Anna; Francis, Brian A; Tan, Ou; Varma, Rohit; Greenfield, David S; Schuman, Joel S; Sehi, Mitra; Chopra, Vikas; Huang, David

2016-12-01

To identify baseline structural parameters that predict the progression of visual field (VF) loss in patients with open-angle glaucoma. Multicenter cohort study. Participants from the Advanced Imaging for Glaucoma (AIG) study were enrolled and followed up. VF progression is defined as either a confirmed progression event on Humphrey Progression Analysis or a significant (P < .05) negative slope for VF index (VFI). Fourier-domain optical coherence tomography (FDOCT) was used to measure optic disc, peripapillary retinal nerve fiber layer (NFL), and macular ganglion cell complex (GCC) thickness parameters. A total of 277 eyes of 188 participants were followed up for 3.7 ± 2.1 years. VF progression was observed in 83 eyes (30%). Several baseline NFL and GCC parameters, but not disc parameters, were found to be significant predictors of progression on univariate Cox regression analysis. The most accurate single predictors were the GCC focal loss volume (FLV), followed closely by NFL-FLV. An abnormal GCC-FLV at baseline increased risk of progression by a hazard ratio of 3.1. Multivariate Cox analysis showed that combining age and central corneal thickness with GCC-FLV in a composite index called "Glaucoma Composite Progression Index" (GCPI) further improved the accuracy of progression prediction. GCC-FLV and GCPI were both found to be significantly correlated with the annual rate of change in VFI. Focal GCC and NFL loss as measured by FDOCT are the strongest predictors for VF progression among the measurements considered. Older age and thinner central corneal thickness can enhance the predictive power using the composite risk model. Copyright © 2016 Elsevier Inc. All rights reserved.

Application of Nanostructures in Electrochromic Materials and Devices: Recent Progress.

PubMed

Wang, Jin Min; Sun, Xiao Wei; Jiao, Zhihui

2010-11-26

The recent progress in application of nanostructures in electrochromic materials and devices is reviewed. ZnO nanowire array modified by viologen and WO₃, crystalline WO₃ nanoparticles and nanorods, mesoporous WO₃ and TiO₂, poly(3,4-ethylenedioxythiophene) nanotubes, Prussian blue nanoinks and nanostructures in switchable mirrors are reviewed. The electrochromic properties were significantly enhanced by applying nanostructures, resulting in faster switching responses, higher stability and higher optical contrast. A perspective on the development trends in electrochromic materials and devices is also proposed.

Effect of vernolide-A, a sesquiterpene lactone from Vernonia cinerea L., on cell-mediated immune response in B16F-10 metastatic melanoma-bearing mice.

PubMed

Pratheeshkumar, P; Kuttan, Girija

2011-09-01

One of the major reasons for the rapid progression of cancers is the ability of tumor cells to escape from the immune surveillance mechanism of the body. Modulation of immune responses is highly relevant in tumor cell destruction. Effect of vernolide-A on the cell-mediated immune (CMI) response in metastatic condition was studied using C57BL/6 mice model. Administration of vernolide-A enhanced natural killer (NK) cell activity, antibody-dependent cellular cytotoxicity (ADCC), and antibody-dependent complement-mediated cytotoxicity (ACC) and the activity was observed in treated group much earlier compared with the metastatic tumor-bearing control. Administration of vernolide-A significantly enhanced the production of interleukin (IL)-2 and interferon-gamma (IFN-γ) in metastatic tumor-bearing animals. In addition, vernolide-A significantly down-regulated the serum levels of proinflammatory cytokines such as IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) during metastasis. All these results demonstrate that vernolide-A could enhance the immune response against metastatic progression of B16F-10 melanoma cells in mice.

TOP1MT deficiency promotes GC invasion and migration via the enhancements of LDHA expression and aerobic glycolysis.

PubMed

Wang, Hongqiang; Zhou, Rui; Sun, Li; Xia, Jianling; Yang, Xuchun; Pan, Changqie; Huang, Na; Shi, Min; Bin, Jianping; Liao, Yulin; Liao, Wangjun

2017-11-01

Aerobic glycolysis plays an important role in cancer progression. New target genes regulating cancer aerobic glycolysis must be explored to improve patient prognosis. Mitochondrial topoisomerase I ( TOP1MT ) deficiency suppresses glucose oxidative metabolism but enhances glycolysis in normal cells. Here, we examined the role of TOP1MT in gastric cancer (GC) and attempted to determine the underlying mechanism. Using in vitro and in vivo experiments and analyzing the clinicopathological characteristics of patients with GC, we found that TOP1MT expression was lower in GC samples than in adjacent nonmalignant tissues. TOP1MT knockdown significantly promoted GC migration and invasion in vitro and in vivo Importantly, TOP1MT silencing increased glucose consumption, lactate production, glucose transporter 1 expression and the epithelial-mesenchymal transition (EMT) in GC. Additionally, regulation of glucose metabolism induced by TOP1MT was significantly associated with lactate dehydrogenase A (LDHA) expression. A retrospective analysis of clinical data from 295 patients with GC demonstrated that low TOP1MT expression was associated with lymph node metastasis, recurrence and high mortality rates. TOP1MT deficiency enhanced glucose aerobic glycolysis by stimulating LDHA to promote GC progression. © 2017 The authors.

AUTEN-67 (Autophagy Enhancer-67) Hampers the Progression of Neurodegenerative Symptoms in a Drosophila model of Huntington's Disease.

PubMed

Billes, Viktor; Kovács, Tibor; Hotzi, Bernadette; Manzéger, Anna; Tagscherer, Kinga; Komlós, Marcell; Tarnóci, Anna; Pádár, Zsolt; Erdős, Attila; Bjelik, Annamaria; Legradi, Adam; Gulya, Károly; Gulyás, Balázs; Vellai, Tibor

2016-05-07

Autophagy, a lysosome-mediated self-degradation process of eukaryotic cells, serves as a main route for the elimination of cellular damage [1-3]. Such damages include aggregated, oxidized or misfolded proteins whose accumulation can cause various neurodegenerative pathologies, including Huntington's disease (HD). Here we examined whether enhanced autophagic activity can alleviate neurophatological features in a Drosophila model of HD (the transgenic animals express a human mutant Huntingtin protein with a long polyglutamine repeat, 128Q). We have recently identified an autophagy-enhancing small molecule, AUTEN-67 (autophagy enhancer 67), with potent neuroprotective effects [4]. AUTEN-67 was applied to induce autophagic activity in the HD model used in this study. We showed that AUTEN-67 treatment interferes with the progressive accumulation of ubiquitinated proteins in the brain of Drosophila transgenic for the pathological 128Q form of human Huntingtin protein. The compound significantly improved the climbing ability and moderately extended the mean life span of these flies. Furthermore, brain tissue samples from human patients diagnosed for HD displayed increased levels of the autophagy substrate SQSTM1/p62 protein, as compared with controls. These results imply that AUTEN-67 impedes the progression of neurodegenerative symptoms characterizing HD, and that autophagy is a promising therapeutic target for treating this pathology. In humans, AUTEN-67 may have the potential to delay the onset and decrease the severity of HD.

Kinetic activity, membrane mitochondrial potential, lipid peroxidation, intracellular pH and calcium of frozen/thawed bovine spermatozoa treated with metabolic enhancers.

PubMed

Boni, R; Gallo, A; Cecchini, S

2017-01-01

Owing to the progressive decline of sperm motility during storage there is a need to find substances capable of enhancing sperm energy metabolism and motility and/or preserving it from oxidative damage. The aim of this study was to evaluate in frozen/thawed bovine spermatozoa the effect of several compounds, such as myo-inositol, pentoxifylline, penicillamine + hypotaurine + epinephrine mixture (PHE), caffeine and coenzyme Q10+ zinc + d-aspartate mixture (CZA), on either kinetic or metabolic parameters. Sperm kinetics was evaluated by Sperm Class Analyser whereas specific fluorochromes were used to evaluated mitochondrial membrane potential (MMP), intracellular pH, intracellular calcium concentration and lipid peroxidation. Lipid peroxidation was also evaluated by TBARS analysis. Treatments significantly affected total and progressive motility with different dynamics in relation to the incubation time. After the first hour of incubation, CZA treatment produced the best performance in total and progressive sperm motility as well as in curvilinear velocity, average path velocity and amplitude of head displacement, whereas pentoxifylline stimulated the highest straight-line velocity. MMP showed higher values (p < 0.01) after treatment with pentoxifylline and PHE. Intracytoplasmic calcium concentration and lipid peroxidation were significantly (p < 0.05) affected by the incubation time rather than the treatments. Intracellular pH varied significantly (p < 0.01) in relation to either the incubation time or treatments. In particular, it showed a progressive increase throughout incubation with values in control group significantly higher than in myo-inositol, PHE, caffeine, pentoxifylline and CZA groups (7.37 ± 0.03 vs. 7.29 ± 0.03, 7.28 ± 0.03, 7.26 ± 0.03, 7.22 ± 0.03 and 7.00 ± 0.03, respectively; p < 0.01).; however, among treatments, CZA displayed the lowest values. Significant correlations were found between sperm kinetic and metabolic parameters. These findings provide new comparative information on the effects of putative metabolic enhancers on kinetics and metabolic activities of bovine spermatozoa. In this study, a rapid methodological approach for evaluating sperm quality is proposed. © 2016 American Society of Andrology and European Academy of Andrology.

[The glymphatic system: concept, function and research progresses].

PubMed

Wang, Lin-Hui; Wang, Zi-Lan; Chen, Wen-Yue; Chen, Ming-Jia; Xu, Guang-Yin

2018-02-25

The glymphatic system is a cerebrospinal fluid-interstitial fluid exchange system dependent on the water channel aquaporin-4 polarized on astrocyte endfeet, which is proposed to account for the clearance of abnormal proteins (e.g. β-amyloid) and metabolites (e.g. lactate) from the brain. Accumulating studies have revealed that glymphatic activity during sleep and general anesthesia is dramatically enhanced, while its function is significantly damaged during aging, traumatic brain injury, Alzheimer's disease, stroke, and diabetes. The glymphatic hypothesis is a breakthrough in the field of neuroscience recently, which would considerably enhance our comprehension on the cerebrospinal fluid circulation and its role in the maintenance of brain homeostasis. In this review, we briefly introduced the conceptualization of glymphatic system, summarized the recent progresses, and prospected its future investigation and potential clinical application.

Genome-wide Association Study Implicates PARD3B-based AIDS Restriction

PubMed Central

Nelson, George W.; Lautenberger, James A.; Chinn, Leslie; McIntosh, Carl; Johnson, Randall C.; Sezgin, Efe; Kessing, Bailey; Malasky, Michael; Hendrickson, Sher L.; Pontius, Joan; Tang, Minzhong; An, Ping; Winkler, Cheryl A.; Limou, Sophie; Le Clerc, Sigrid; Delaneau, Olivier; Zagury, Jean-François; Schuitemaker, Hanneke; van Manen, Daniëlle; Bream, Jay H.; Gomperts, Edward D.; Buchbinder, Susan; Goedert, James J.; Kirk, Gregory D.; O'Brien, Stephen J.

2011-01-01

Background. Host genetic variation influences human immunodeficiency virus (HIV) infection and progression to AIDS. Here we used clinically well-characterized subjects from 5 pretreatment HIV/AIDS cohorts for a genome-wide association study to identify gene associations with rate of AIDS progression. Methods.  European American HIV seroconverters (n = 755) were interrogated for single-nucleotide polymorphisms (SNPs) (n = 700,022) associated with progression to AIDS 1987 (Cox proportional hazards regression analysis, co-dominant model). Results.  Association with slower progression was observed for SNPs in the gene PARD3B. One of these, rs11884476, reached genome-wide significance (relative hazard = 0.3; P =3. 370 × 10−9) after statistical correction for 700,022 SNPs and contributes 4.52% of the overall variance in AIDS progression in this study. Nine of the top-ranked SNPs define a PARD3B haplotype that also displays significant association with progression to AIDS (hazard ratio, 0.3; P = 3.220 × 10−8). One of these SNPs, rs10185378, is a predicted exonic splicing enhancer; significant alteration in the expression profile of PARD3B splicing transcripts was observed in B cell lines with alternate rs10185378 genotypes. This SNP was typed in European cohorts of rapid progressors and was found to be protective for AIDS 1993 definition (odds ratio, 0.43, P = .025). Conclusions. These observations suggest a potential unsuspected pathway of host genetic influence on the dynamics of AIDS progression. PMID:21502085

Bevacizumab and fotemustine for recurrent glioblastoma: a phase II study of AINO (Italian Association of Neuro-Oncology).

PubMed

Soffietti, Riccardo; Trevisan, Elisa; Bertero, Luca; Cassoni, Paola; Morra, Isabella; Fabrini, Maria Grazia; Pasqualetti, Francesco; Lolli, Ivan; Castiglione, Anna; Ciccone, Giovannino; Rudà, Roberta

2014-02-01

The optimal combination of bevacizumab with cytotoxic or cytostatic drugs in recurrent glioblastoma is unknown. We performed a phase 2 trial of combined bevacizumab and fotemustine for patients with glioblastoma at first relapse after radiotherapy and temozolomide. The primary endpoint was 6-month progression-free survival (PFS), while secondary endpoints were overall survival (OS), response rate based on RANO criteria and toxicity. Fifty-four patients with recurrent GBM were enrolled. The authors observed a 6-month PFS rate of 42.6% (95% CI 29.3-55.2) and a median PFS of 5.2 months (95% CI 3.8-6.6). The median OS was 9.1 months (95% CI 7.3-10.3). Twenty-eight patients (52%) had a radiographic response, and a significant neurological improvement with steroid reduction was observed in 25/42 symptomatic patients (60%). MGMT promoter methylation was significantly associated with improved PFS in univariate analysis. Most unifocal tumors at baseline had a focal enhancing progression (76%), while the diffuse non-enhancing progression accounted for 9.5%. Response or survival were not associated with any pattern of progression. Survival after failure of treatment was short. Twelve out of 54 patients (22%) discontinued fotemustine for grade 3/4 myelotoxicity, while 4/54 (7.4%) discontinued bevacizumab. This study failed to demonstrate a superiority of the combination of bevacizumab and fotemustine over either bevacizumab or fotemustine alone as historical controls. Future studies should explore alternative regimens of combination of the two drugs.

Effect of quinolinic acid-induced lesions of the subthalamic nucleus on performance on a progressive-ratio schedule of reinforcement: A quantitative analysis

PubMed Central

Bezzina, G.; Boon, F.S. den; Hampson, C.L.; Cheung, T.H.C.; Body, S.; Bradshaw, C.M.; Szabadi, E.; Anderson, I.M.; Deakin, J.F.W.

2008-01-01

The subthalamic nucleus (STN), a major relay in the indirect striatofugal pathway, plays an important role in extrapyramidal motor control. Recent evidence indicates that it may also be involved in regulating the incentive value of food reinforcers. Objective To examine the effect of lesions of the STN on performance on a progressive-ratio schedule using a quantitative model that dissociates effects of interventions on motor and motivational processes [Killeen PR. Mathematical principles of reinforcement. Behav Brain Sci 1994;17:105–72]. Rats with bilateral quinolinic acid-induced lesions of the STN (n = 14) or sham lesions (n = 14) were trained to press a lever for food-pellet reinforcers under a progressive-ratio schedule. In Phase 1 (90 sessions) the reinforcer was one pellet; in Phase 2 (30 sessions) it was two pellets; in Phase 3 (30 sessions) it was again one pellet. Results The performance of both groups conformed to the model of progressive-ratio schedule performance. The motor parameter, δ, was significantly higher in the STN-lesioned than the sham-lesioned group, reflecting lower overall response rates in the lesioned group. The motivational parameter, a, was significantly higher in the STN-lesioned group than in the sham-lesioned group, consistent with enhanced reinforcer value in the STN-lesioned group compared to the sham-lesioned group. In both groups, a was sensitive to changes in reinforcer size, being significantly greater under the two-pellet condition (Phase 2) than under the one-pellet condition (Phases 1 and 3). The results suggest that destruction of the STN impairs response capacity and enhances the incentive value of food reinforcers. PMID:18840473

Increased expression of 78 kD glucose-regulated protein promotes cardiomyocyte apoptosis in a rat model of liver cirrhosis

PubMed Central

Zhang, Lili; Zhang, Huiying; Lv, Minli; Jia, Jiantao; Fan, Yimin; Tian, Xiaoxia; Li, Xujiong; Li, Baohong; Ji, Jingquan; Wang, Limin; Zhao, Zhongfu; Han, Dewu; Ji, Cheng

2015-01-01

Aims: This study was to investigate the role and underlying mechanism of 78 kD glucose-regulated protein (GRP78) in cardiomyocyte apoptosis in a rat model of liver cirrhosis. Methods: A rat model of liver cirrhosis was established with multiple pathogenic factors. A total of 42 male SD rats were randomly divided into the liver cirrhosis group and control group. Cardiac structure analysis was performed to assess alterations in cardiac structure. Cardiomyocytes apoptosis was detected by TdT-mediated dUTP nick end labeling method. Expression of GRP78, CCAAT/enhancer-binding protein homologous protein (CHOP), caspase-12, nuclear factor kappa-light-chain-enhancer of activated B cells p65 subunit (NF-κB p65) and B cell lymphoma-2 (Bcl-2) was detected by immunohistochemical staining. Results: The ratios of left ventricular wall thickness to heart weight and heart weight to body weight were significantly increased with the progression of liver cirrhosis (P < 0.05). Apoptosis index of cardiomyocytes was significantly increased with the progression of liver cirrhosis (P < 0.05). The expression levels of GRP78, CHOP and caspase-12 were significantly increased in the progression of liver cirrhosis (P < 0.05). The expression levels of NF-κB p65 and Bcl-2 were highest in the 4-wk liver cirrhosis, and they were decreased in the 6-wk and 8-wk in the progression of liver cirrhosis. GRP78 expression levels were positively correlated with apoptosis index, CHOP and caspase-12 expression levels (P < 0.05). CHOP expression levels were negatively correlated with NF-κB p65 and Bcl-2 expression levels (P < 0.05). Conclusion: Increased expression of GRP78 promotes cardiomyocyte apoptosis in rats with cirrhotic cardiomyopathy. PMID:26464674

Military Interoperable Digital Hospital Testbed (MIDHT)

DTIC Science & Technology

2010-02-01

note build and system setup. There was significant progress in identifying workflows and processes. A sample note for a patient visit can be seen...between EMR systems did not exist when surveys were completed in early 2009. There is a significant opportunity to enhance patient care of military...interpret the provider’s handwriting . Many EHRs have included decision support into their functionality to help alert physicians to medication conflicts

Microchannel Plate Imaging Detectors for the Ultraviolet

NASA Technical Reports Server (NTRS)

Siegmund, O. H. W.; Gummin, M. A.; Stock, J.; Marsh, D.

1992-01-01

There has been significant progress over the last few years in the development of technologies for microchannel plate imaging detectors in the Ultraviolet (UV). Areas where significant developments have occurred include enhancements of quantum detection efficiency through improved photocathodes, advances in microchannel plate performance characteristics, and development of high performance image readout techniques. The current developments in these areas are summarized, with their applications in astrophysical instrumentation.

Permeability estimates in histopathology-proved treatment-induced necrosis using perfusion CT: can these add to other perfusion parameters in differentiating from recurrent/progressive tumors?

PubMed

Jain, R; Narang, J; Schultz, L; Scarpace, L; Saksena, S; Brown, S; Rock, J P; Rosenblum, M; Gutierrez, J; Mikkelsen, T

2011-04-01

Differentiating treatment effects from RPT is a common yet challenging task in a busy neuro-oncologic practice. PS probably represents a different aspect of angiogenesis and vasculature and can provide additional physiologic information about recurrent/progressive enhancing lesions. The purpose of the study was to use PS measured by using PCT to differentiate TIN from RPT in patients with previously irradiated brain tumor who presented with a recurrent/progressive enhancing lesion. Seventy-two patients underwent PCT for assessment of a recurrent/progressive enhancing lesion from January 2006 to November 2009. Thirty-eight patients who underwent surgery and histopathologic diagnosis were included in this analysis. Perfusion parameters such as PS, CBV, CBF, and MTT were obtained from the enhancing lesion as well as from the NAWM. Of 38 patients, 11 were diagnosed with pure TIN and 27 had RPT. Patients with TIN showed significantly lower mean PS values than those with RPT (1.8 ± 0.8 versus 3.6 ± 1.6 mL/100 g/min; P value=.001). The TIN group also showed lower rCBV (1.2 ± 0.3 versus 2.1 ± 0.7; P value<.001), lower rCBF (1.2 ± 0.5 versus 2.6 ± 1.7; P value=.004), and higher rMTT (1.4 ± 0.4 versus 1.0 ± 0.4; P value=.018) compared with the RPT group. PCT and particularly PS can be used in patients with previously treated brain tumors to differentiate TIN from RPT. PS estimates can help increase the accuracy of PCT in differentiating these 2 entities.

Environmental heat stress enhances mental fatigue during sustained attention task performing: evidence from an ASL perfusion study.

PubMed

Qian, Shaowen; Li, Min; Li, Guoying; Liu, Kai; Li, Bo; Jiang, Qingjun; Li, Li; Yang, Zhen; Sun, Gang

2015-03-01

This study was to investigate the potential enhancing effect of heat stress on mental fatigue progression during sustained attention task using arterial spin labeling (ASL) imaging. Twenty participants underwent two thermal exposures in an environmental chamber: normothermic (NT) condition (25°C, 1h) and hyperthermic (HT) condition (50°C, 1h). After thermal exposure, they performed a twenty-minute psychomotor vigilance test (PVT) in the scanner. Behavioral analysis revealed progressively increasing subjective fatigue ratings and reaction time as PVT progressed. Moreover, heat stress caused worse performance. Perfusion imaging analyses showed significant resting-state cerebral blood flow (CBF) alterations after heat exposure. Specifically, increased CBF mainly gathered in thalamic-brainstem area while decreased CBF predominantly located in fronto-parietal areas, anterior cingulate cortex, posterior cingulate cortex, and medial frontal cortex. More importantly, diverse CBF distributions and trend of changes between both conditions were observed as the fatigue level progressed during subsequent PVT task. Specifically, higher CBF and enhanced rising trend were presented in superior parietal lobe, precuneus, posterior cingulate cortex and anterior cingulate cortex, while lower CBF or inhibited rising trend was found in dorsolateral frontal cortex, medial frontal cortex, inferior parietal lobe and thalamic-brainstem areas. Furthermore, the decrease of post-heat resting-state CBF in fronto-parietal cortex was correlated with subsequent slower reaction time, suggesting prior disturbed resting-state CBF might be indicator of performance potential and fatigue level in following task. These findings may provide proof for such a view: heat stress has a potential fatigue-enhancing effect when individual is performing highly cognition-demanding attention task. Copyright © 2014 Elsevier B.V. All rights reserved.

CO 2 elevation improves photosynthetic performance in progressive warming environment in white birch seedlings.

PubMed

Zhang, Shouren; Dang, Qing-Lai

2013-01-01

White birch (Betula paperifera Mash) seedlings were exposed to progressively warming in greenhouses under ambient and elevated CO 2 concentrations for 5 months to explore boreal tree species' potential capacity to acclimate to global climate warming and CO 2 elevation. In situ foliar gas exchange, in vivo carboxylation characteristics and chlorophyll fluorescence were measured at temperatures of 26 (o)C and 37 (o)C. Elevated CO 2 significantly increased net photosynthetic rate (Pn) at both measurement temperatures, and Pn at 37 (o)C was higher than that at 26 (o)C under elevated CO 2. Stomatal conductance (gs) was lower at 37 (o)C than at 26 (o)C, while transpiration rate (E) was higher at 37 (o)C than that at 26 (o)C. Elevated CO 2 significantly increased instantaneous water-use efficiency (WUE) at both 26 (o)C and 37 (o)C, but WUE was markedly enhanced at 37 (o)C under elevated CO 2. The effect of temperature on maximal carboxylation rate (Vcmax), PAR-saturated electron transport rate (Jmax) and triose phosphate utilization (TPU) varied with CO 2, and the Vcmax and Jmax were significantly higher at 37 (o)C than at 26 (o)C under elevated CO 2. However, there were no significant interactive effects of CO 2 and temperature on TPU. The actual photochemical efficiency of PSII (DF/ Fm'), total photosynthetic linear electron transport rate through PSII (JT) and the partitioning of JT to carboxylation (Jc) were higher at 37 (o)C than at 26 (o)C under elevated CO 2. Elevated CO 2 significantly suppressed the partitioning of JT to oxygenation (Jo/JT). The data suggest that the CO 2 elevation and progressive warming greatly enhanced photosynthesis in white birch seedlings in an interactive fashion.

Application of Nanostructures in Electrochromic Materials and Devices: Recent Progress

PubMed Central

Wang, Jinmin; Sun, Xiao Wei; Jiao, Zhihui

2010-01-01

The recent progress in application of nanostructures in electrochromic materials and devices is reviewed. ZnO nanowire array modified by viologen and WO3, crystalline WO3 nanoparticles and nanorods, mesoporous WO3 and TiO2, poly(3,4-ethylenedioxythiophene) nanotubes, Prussian blue nanoinks and nanostructures in switchable mirrors are reviewed. The electrochromic properties were significantly enhanced by applying nanostructures, resulting in faster switching responses, higher stability and higher optical contrast. A perspective on the development trends in electrochromic materials and devices is also proposed. PMID:28883368

Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection--The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index.

PubMed

Rollet-Kurhajec, Kathleen C; Moodie, Erica E M; Walmsley, Sharon; Cooper, Curtis; Pick, Neora; Klein, Marina B

2015-01-01

In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA. Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed.

Most recent developments in strategies to reduce the progression of structural changes in osteoarthritis: today and tomorrow

PubMed Central

Pelletier, Jean-Pierre; Martel-Pelletier, Johanne; Raynauld, Jean-Pierre

2006-01-01

Osteoarthritis (OA), the most common of all arthritic conditions, is a social and financial burden to all nations. The most recent research has significantly advanced our understanding of the cause of OA and risk factors associated with it. These findings have provided useful information that has helped in the daily management of patients with OA. Some preventative measures and a number of therapeutic agents and drugs are available, which may help to reduce the progression of OA in certain patients. Moreover, the most recent progress in research has significantly enhanced our knowledge of the factors involved in the development of the disease and of the mechanisms responsible for its progression. This has allowed identification of several new therapeutic targets in a number of pathophysiological pathways. Consequently, the field is opening up to a new era in which drugs and agents that can specifically block important mechanisms responsible for the structural changes that occur in OA can be brought into development and eventually into clinical trials. PMID:16569256

Open Classroom: Enhancing Student Achievement on Artificial Intelligence through an International Online Competition

ERIC Educational Resources Information Center

Carpio Cañada, J.; Mateo Sanguino, T. J.; Merelo Guervós, J. J.; Rivas Santos, V. M.

2015-01-01

Limitations of formal learning (e.g., one-way communication, rigid methodology, results-oriented approach) can significantly influence the motivation and expectation of students, thus resulting in an academic progress reduction. In order to make learning processes more playful and motivating, this paper presents a new educational experience…

Scorpion venom peptide SPVII promotes irradiated cells proliferation and increases the expression of the IL-3 receptor

PubMed Central

2013-01-01

Background The previous investigation demonstrated the radioprotective efficacy of peptides isolated from the venom of Buthus Martti Karsch. In this study, the effect of isolated scorpion venom peptide II (SVPII) on irradiated M-NFS-60 cells and mouse bone marrow mononuclear cells (BM-MNCs) was observed. The AlamarBlue cell viability assay, a colony-forming unit (CFU) assay, flow cytometry (FCM), immunofluorescence, and Western blotting were used to evaluate cell proliferation, cell cycle progression, and the expression of the IL-3 receptor (IL-3R) protein in non-irradiated and irradiated cells. Results Proliferation of irradiated M-NFS-60 cells was significantly accelerated by SPVII, and this effect was further enhanced by co-application of IL-3. Similarly, SPVII increased the number of BM-MNC CFUs and this proliferative effect was greater in the presence of SVPII plus IL-3. In addition, SPVII significantly altered cell cycle progression; SVPII enhanced the fraction of unirradiated M-NFS-60 cells in S phase and the fraction of irradiated M-NFS-60 cells arrested in G2/M. The expression of IL-3R protein by unirradiated M-NFS-60 cells was enhanced significantly by SVPII, and SVPII-induced IL-3R overexpression was 10-fold greater in irradiated M-NFS-60 cells. Conclusions These results indicated the hematopoietic growth factor (HGF)-like effects of SVPII on irradiated cells, possibly mediated by upregulation of IL-3R. PMID:23835458

Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells

PubMed Central

Okumura, Takashi; Ohuchida, Kenoki; Sada, Masafumi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Iwamoto, Chika; Miura, Daisuke; Mizuuchi, Yusuke; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

2017-01-01

Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells. PMID:28407685

Students, Teachers, and Schools as Sources of Variability, Integrity, and Sustainability in Implementing Progress Monitoring

ERIC Educational Resources Information Center

Bolt, Daniel M.; Ysseldyke, Jim; Patterson, Michael J.

2010-01-01

A three-level variance decomposition analysis was used to examine the sources of variability in implementation of a technology-enhanced progress monitoring system within each year of a 2-year study using a randomized-controlled design. We show that results of technology-enhanced progress monitoring are not necessarily a measure of student…

Potential for differentiation of pseudoprogression from true tumor progression with dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging using ferumoxytol versus gadoteridol: A pilot study

PubMed Central

Gahramanov, Seymur; Raslan, Ahmed; Muldoon, Leslie L.; Hamilton, Bronwyn E.; Rooney, William D.; Varallyay, Csanad G.; Njus, Jeffrey M.; Haluska, Marianne; Neuwelt, Edward A.

2010-01-01

Purpose We evaluated dynamic susceptibility-weighted contrast-enhanced magnetic resonance imaging (DSC-MRI) using gadoteridol in comparison to the iron oxide nanoparticle blood pool agent, ferumoxytol in patients with glioblastoma multiforme (GBM) who received standard radiochemotherapy (RCT). Methods and Materials Fourteen patients with GBM received standard RCT and underwent 19 MRI sessions that included DSC-MRI acquisitions with gadoteridol on day 1 and ferumoxytol on day 2. Relative cerebral blood volume (rCBV) values were calculated from DSC data obtained from each contrast agent. T1-weighted acquisition post-gadoteridol administration was used to identify enhancing regions. Results In 7 MRI sessions of clinically presumptive active tumor, gadoteridol-DSC showed low rCBV in 3 and high rCBV in 4, while ferumoxytol-DSC showed high rCBV in all 7 sessions (p=0.002). After RCT, 7 MRI sessions showed increased gadoteridol contrast enhancement on T1-weighted scans coupled with low rCBV without significant differences between contrast agents (p=0.9). Based on post-gadoteridol T1-weighted scans, DSC-MRI, and clinical presentation four patterns of response to RCT were observed: 1) regression, 2) pseudoprogression, 3) true progression, and 4) mixed response. Conclusion We conclude that DSC-MRI with a blood-pool agent such as ferumoxytol may provide a better monitor of tumor rCBV than DSC-MRI with gadoteridol. Lesions demonstrating increased enhancement on T1-weighted MRI coupled with low ferumoxytol rCBV, are likely exhibiting pseudoprogression, while high rCBV with ferumoxytol is a better marker than gadoteridol for determining active tumor. These interesting pilot observations suggest that ferumoxytol may differentiate tumor progression from pseudoprogression, and warrant further investigation. PMID:20395065

Defective photoreceptor phagocytosis in a mouse model of enhanced S-cone syndrome causes progressive retinal degeneration

PubMed Central

Mustafi, Debarshi; Kevany, Brian M.; Genoud, Christel; Okano, Kiichiro; Cideciyan, Artur V.; Sumaroka, Alexander; Roman, Alejandro J.; Jacobson, Samuel G.; Engel, Andreas; Adams, Mark D.; Palczewski, Krzysztof

2011-01-01

Enhanced S-cone syndrome (ESCS), featuring an excess number of S cones, manifests as a progressive retinal degeneration that leads to blindness. Here, through optical imaging, we identified an abnormal interface between photoreceptors and the retinal pigment epithelium (RPE) in 9 patients with ESCS. The neural retina leucine zipper transcription factor-knockout (Nrl−/−) mouse model demonstrates many phenotypic features of human ESCS, including unstable S-cone-positive photoreceptors. Using massively parallel RNA sequencing, we identified 6203 differentially expressed transcripts between wild-type (Wt) and Nrl−/− mouse retinas, with 6 highly significant differentially expressed genes of the Pax, Notch, and Wnt canonical pathways. Changes were also obvious in expression of 30 genes involved in the visual cycle and 3 key genes in photoreceptor phagocytosis. Novel high-resolution (100 nm) imaging and reconstruction of Nrl−/− retinas revealed an abnormal packing of photoreceptors that contributed to buildup of photoreceptor deposits. Furthermore, lack of phagosomes in the RPE layer of Nrl−/− retina revealed impairment in phagocytosis. Cultured RPE cells from Wt and Nrl−/− mice illustrated that the phagocytotic defect was attributable to the aberrant interface between ESCS photoreceptors and the RPE. Overcoming the retinal phagocytosis defect could arrest the progressive degenerative component of this disease.—Mustafi, D., Kevany, B. M., Genoud, C., Okano, K., Cideciyan, A. V., Sumaroka, A., Roman, A. J., Jacobson, S. G. Engel, A., Adams, M. D., Palczewski, K. Defective photoreceptor phagocytosis in a mouse model of enhanced S-cone syndrome causes progressive retinal degeneration. PMID:21659555

Imaging of intrahepatic progression of hepatocellular carcinoma post transarterial chemoembolization. A long-term, prospective evaluation of contrast-enhanced ultrasonography (CEUS).

PubMed

Moschouris, Hippocrates; Kalokairinou-Motogna, Mariana; Vrakas, Spyros; Papadatou, Aggeliki; Karagiannis, Eyaggelos; Kiltenis, Michail; Kladis-Kalentzis, Konstantinos; Marmaridou, Kyriaki; Papadogeorgopoulos, Nikolaos; Malagari, Katerina

2017-04-22

To assess the diagnostic efficacy of contrast-enhanced ultrasonography (CEUS) in the context of intrahepatic progression (IHP) of hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Sixty HCC patients were prospectively included in the study. They were treated with transarterial chemoembolization (TACE)with doxorubicin-eluting microspheres (231 sessions). Imaging follow-up was performed 1 month after each session and at 3-6 month intervals after the last session of TACE and included CEUS and contrast-enhanced magnetic resonance (MR) imaging (reference modality). The diagnosis of IHP was based on mRECIST criteria and the respective findings of MR and CEUS were recorded, categorized and correlated. A total of 441 CEUS studies were compared with the corresponding MR studies. During a follow-up period of 5-82 months (mean: 22 months), MR diagnosed 51 cases of IHP in 34/60 (56.6%) patients. CEUS correctly diagnosed 12/14 (85.7%) cases of IHP of target tumors, 2/5 (40%) cases of IHP of non-target tumors, 13/18 (72.2%) cases of distal and 6/9 (66.6%) cases of proximal new lesions, and 5/5 (100%) cases of major vessel involvement. On a per-lesion basis, CEUS was significantly inferior to MR in the detection of new lesions (p=0.002). No false positive CEUS diagnoses of IHP were observed. 54% of the diagnostic failures of CEUS were considered clinically significant.  In the long term evaluation of HCC post TACE, CEUS appears to have limitations in the detection of IHP, which are more prominent in the case of new lesions and of progressive non-target tumors.

Career progress in online and blended learning environments.

PubMed

DeRosier, Melissa; Kameny, Rebecca; Holler, Wendy; Davis, Naomi Ornstein; Maschauer, Emily

2013-03-01

The authors examined the career achievement of early- and mid-career researchers in social, behavioral, and mental health who participated in a career-development conference. Trainees participated in a career-development conference either through attending a live conference supplemented with an online version of the conference (Combined: N=46) or through the online version of the conference alone (Web-Only: N=60). An objective measure tracked the trainees' publications, involvement in research projects, honors and grant awards, collaborations, and scientific presentations before and 9 months after participation in the career-development conference. Statistical analysis showed that trainees improved for each category measured, with no significant differences across the Combined and Web-Only groups. The strongest variable affecting improvement was Time, and the most significant time effect was seen in the production of presentations and publications. A significant Gender difference was present, with women showing greater total career progress than men. Career-development conferences can support career growth for trainees. Online training provides a cost-effective and time-efficient alternative to in-person methods, while still enhancing key markers of career progress.

Effect of Technology-Enhanced Continuous Progress Monitoring on Math Achievement

ERIC Educational Resources Information Center

Ysseldyke, Jim; Bolt, Daniel M.

2007-01-01

We examined the extent to which use of a technology-enhanced continuous progress monitoring system would enhance the results of math instruction, examined variability in teacher implementation of the program, and compared math results in classrooms in which teachers did and did not use the system. Classrooms were randomly assigned to within-school…

Guided filtering for solar image/video processing

NASA Astrophysics Data System (ADS)

Xu, Long; Yan, Yihua; Cheng, Jun

2017-06-01

A new image enhancement algorithm employing guided filtering is proposed in this work for the enhancement of solar images and videos so that users can easily figure out important fine structures embedded in the recorded images/movies for solar observation. The proposed algorithm can efficiently remove image noises, including Gaussian and impulse noises. Meanwhile, it can further highlight fibrous structures on/beyond the solar disk. These fibrous structures can clearly demonstrate the progress of solar flare, prominence coronal mass emission, magnetic field, and so on. The experimental results prove that the proposed algorithm gives significant enhancement of visual quality of solar images beyond original input and several classical image enhancement algorithms, thus facilitating easier determination of interesting solar burst activities from recorded images/movies.

Progressive disease in glioblastoma: Benefits and limitations of semi-automated volumetry

PubMed Central

Alber, Georgina; Bette, Stefanie; Kaesmacher, Johannes; Boeckh-Behrens, Tobias; Gempt, Jens; Ringel, Florian; Specht, Hanno M.; Meyer, Bernhard; Zimmer, Claus

2017-01-01

Purpose Unambiguous evaluation of glioblastoma (GB) progression is crucial, both for clinical trials as well as day by day routine management of GB patients. 3D-volumetry in the follow-up of GB provides quantitative data on tumor extent and growth, and therefore has the potential to facilitate objective disease assessment. The present study investigated the utility of absolute changes in volume (delta) or regional, segmentation-based subtractions for detecting disease progression in longitudinal MRI follow-ups. Methods 165 high resolution 3-Tesla MRIs of 30 GB patients (23m, mean age 60.2y) were retrospectively included in this single center study. Contrast enhancement (CV) and tumor-related signal alterations in FLAIR images (FV) were semi-automatically segmented. Delta volume (dCV, dFV) and regional subtractions (sCV, sFV) were calculated. Disease progression was classified for every follow-up according to histopathologic results, decisions of the local multidisciplinary CNS tumor board and a consensus rating of the neuro-radiologic report. Results A generalized logistic mixed model for disease progression (yes / no) with dCV, dFV, sCV and sFV as input variables revealed that only dCV was significantly associated with prediction of disease progression (P = .005). Delta volume had a better accuracy than regional, segmentation-based subtractions (79% versus 72%) and a higher area under the curve by trend in ROC curves (.83 versus .75). Conclusion Absolute volume changes of the contrast enhancing tumor part were the most accurate volumetric determinant to detect progressive disease in assessment of GB and outweighed FLAIR changes as well as regional, segmentation-based image subtractions. This parameter might be useful in upcoming objective response criteria for glioblastoma. PMID:28245291

Monoclonal antibody Zt/g4 targeting RON receptor tyrosine kinase enhances chemosensitivity of bladder cancer cells to Epirubicin by promoting G1/S arrest and apoptosis.

PubMed

Chen, Jun-Feng; Yu, Bi-Xia; Yu, Rui; Ma, Liang; Lv, Xiu-Yi; Cheng, Yue; Ma, Qi

2017-02-01

Epirubicin (EPI) is one of the most used intravesical chemotherapy agents after transurethral resection to non-muscle invasive bladder tumors (NMIBC) to prevent cancer recurrence and progression. However, even after resection of bladder tumors and intravesical chemotherapy, half of them will recur and progress. RON is a membrane tyrosine kinase receptor usually overexpressed in bladder cancer cells and associated with poor pathological features. This study aims to investigate the effects of anti-RON monoclonal antibody Zt/g4 on the chemosensitivity of bladder cells to EPI. After Zt/g4 treatment, cell cytotoxicity was significantly increased and cell invasion was markedly suppressed in EPI-treated bladder cancer cells. Further investigation indicated that combing Zt/g4 with EPI promoted cell G1/S-phase arrest and apoptosis, which are the potential mechanisms that RON signaling inhibition enhances chemosensitivity of EPI. Thus, combing antibody-based RON targeted therapy enhances the therapeutic effects of intravesical chemotherapy, which provides new strategy for further improvement of NMIBC patient outcomes.

Co-amplification of phosphoinositide 3-kinase enhancer A and cyclin-dependent kinase 4 triggers glioblastoma progression | Office of Cancer Genomics

Cancer.gov

Glioblastoma (GBM) is the most common primary brain tumor and has a dismal prognosis. Amplification of chromosome 12q13-q15 (Cyclin-dependent kinase 4 (CDK4) amplicon) is frequently observed in numerous human cancers including GBM. Phosphoinositide 3-kinase enhancer (PIKE) is a group of GTP-binding proteins that belong to the subgroup of centaurin GTPase family, encoded by CENTG1 located in CDK4 amplicon. However, the pathological significance of CDK4 amplicon in GBM formation remains incompletely understood.

Leupaxin acts as a mediator in prostate carcinoma progression through deregulation of p120catenin expression.

PubMed

Kaulfuss, S; von Hardenberg, S; Schweyer, S; Herr, A M; Laccone, F; Wolf, S; Burfeind, P

2009-11-12

Recently, we could show that the focal adhesion protein leupaxin (LPXN) is expressed in human prostate carcinomas (PCa) and induces invasiveness of androgen-independent PCa cells. In this study we show that LPXN enhanced the progression of existing PCa in vivo by breeding transgenic mice with prostate-specific LPXN expression and TRAMP mice (transgenic adenocarcinoma of mouse prostate). Double transgenic LPXN/TRAMP mice showed a significant increase in poorly differentiated PCa and distant metastases as compared with control TRAMP mice. Additional studies on primary PCa cells generated from both transgenic backgrounds confirmed the connection regarding LPXN overexpression and increased motility and invasiveness of PCa cells. One mediator of LPXN-induced invasion was found to be the cell-cell adhesion protein p120catenin (p120CTN). Both in vitro and in vivo experiments revealed that p120CTN expression negatively correlates with LPXN expression, followed by a redistribution of beta-catenin. Downregulation of LPXN using small interfering RNAs (siRNAs) resulted in a membranous localization of beta-catenin, whereas strong nuclear accumulation of beta-catenin was observed in p120CTN knockdown cells leading to enhanced transcription of the beta-catenin target gene matrix metalloprotease-7. In conclusion, the present results indicate that LPXN enhances the progression of PCa through downregulation of p120CTN expression and that LPXN could function as a marker for aggressive PCa in the future.

Toward Teaching Methods that Develop Learning and Enhance Problem Solving Skills in Engineering Students

ERIC Educational Resources Information Center

Loji, K.

2012-01-01

Problem solving skills and abilities are critical in life and more specifically in the engineering field. Unfortunately, significant numbers of South African students who are accessing higher education lack problem solving skills and this results in poor academic performance jeopardizing their progress especially from first to second year. On the…

Increased accumulation of 4-hydroxynonenal adducts in female GSTA4/PPAR alpha double knockout mice enhance steatosis and inflammation in a model of pediatric nonalcoholic fatty liver disease

USDA-ARS?s Scientific Manuscript database

Hepatocellular injury resulting from increased lipid peroxidation products and oxidative stress is considered a potential mechanism driving the progression of nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitsis (NASH). To test the significance of lipid peroxidation and protein...

mRECIST criteria and contrast-enhanced US for the assessment of the response of hepatocellular carcinoma to transarterial chemoembolization

PubMed Central

Moschouris, Hippocrates; Malagari, Katerina; Papadaki, Marina G.; Kornezos, Ioannis; Stamatiou, Konstantinos; Anagnostopoulos, Antonios; Chatzimichael, Katerina; Kelekis, Nikolaos

2014-01-01

PURPOSE We aimed to evaluate the combination of the modified Response Evaluation Criteria In Solid Tumors (mRECIST) and contrast-enhanced ultrasonography (CEUS) as a tool for the assessment of hepatocellular carcinoma treated with transarterial chemoembolization. MATERIALS AND METHODS Forty-seven hepatocellular carcinoma patients (80 target tumors suitable for mRECIST measurements) were studied. They were treated with scheduled transarterial chemoembolization with doxorubicin-eluting microspheres every 5–7 weeks. Imaging follow-up (performed one month after each transarterial chemoembolization) included a standard, contrast-enhanced modality (computed tomography [CT] in 12 patients or magnetic resonance imaging [MRI] in 35 patients) and CEUS. The study focused on response evaluation after the third transarterial chemoembolization. CEUS required a bolus injection of an echo-enhancer and imaging with a dedicated, low mechanical index technique. The longest diameters of the enhancing target tumors were measured on the CEUS or CT/MRI, and mRECIST criteria were applied. Radiologic responses were correlated with overall survival and time to progression. RESULTS The measurements of longest diameters of the enhancing target tumors were easily performed in all patients. According to mRECIST-CEUS and mRECIST-CT/MRI, complete response was recorded in five and six patients, partial response in 22 and 21 patients, stable disease in 16 and 14 patients, and progressive disease in four and six patients, respectively. There was a high degree of concordance between CEUS and CT/MRI (kappa coefficient=0.84, P < 0.001). Responders (complete+partial response) according to mRECIST-CEUS had a significantly longer mean overall survival and time to progression compared to nonresponders (37.1 vs. 11.0 months, P < 0.001 and 24.6 vs. 10.9 months, P = 0.007, respectively). CONCLUSION The mRECIST-CEUS combination is feasible and has prognostic value in the assessment of hepatocellular carcinoma following transarterial chemoembolization. PMID:24317334

The effect of melatonin on the quality of extended boar semen after long-term storage at 17 °C.

PubMed

Martín-Hidalgo, D; Barón, F J; Bragado, M J; Carmona, P; Robina, A; García-Marín, L J; Gil, M C

2011-05-01

Melatonin (MLT) is an efficient antioxidant that protects cells and tissues and initiates a host of receptor-mediated effects. In order to enhance the life span of refrigerated boar semen, our aim was to evaluate the effects of addition of 1 μM MLT to commercially produced pig semen (33 seminal doses from 14 boars) that had been preserved at 17 °C for 7 days. Samples without MLT served as controls. On Days 1, 4 and 7, we evaluated motility parameters and the percentage of total motile and progressively motile spermatozoa by a computer-aided sperm analysis system. Viability (SYBR-14/PI), acrosomal status (FITC-PNA/PI), membrane fluidity (M-540/YoPro-1) and mitochondrial membrane potential status (JC-1) were evaluated by flow cytometry. MLT treatment significantly enhanced the percentage of static spermatozoa after 7 days of storage and significantly reduced the percentage of progressively motile spermatozoa on Day 7. The velocity characteristics (VCL, VSL and VAP) were significantly higher for MLT-treated samples on Day 1 and were their lowest on Day 7. With regard to flow cytometry results, the percentage of viable spermatozoa with an intact acrosome was higher in MLT samples throughout the entire storage period. In addition, there was a significantly higher proportion of live spermatozoa on Day 7 in the samples that had not been treated with MLT. The proportion of spermatozoa showing a high mitochondrial membrane potential remained at similar levels (P > 0.05) throughout the trial. Although the findings of the present study revealed that 1 μM MLT increased the proportion of live sperm with an intact acrosome, this treatment did not enhance the spermatic quality of refrigerated boar semen. Copyright © 2011 Elsevier Inc. All rights reserved.

True progression versus pseudoprogression in the treatment of glioblastomas: a comparison study of normalized cerebral blood volume and apparent diffusion coefficient by histogram analysis.

PubMed

Song, Yong Sub; Choi, Seung Hong; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm(2)). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10(-6) mm(2)/sec for observer 1 and 907 × 10(-6) mm(2)/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas.

True Progression versus Pseudoprogression in the Treatment of Glioblastomas: A Comparison Study of Normalized Cerebral Blood Volume and Apparent Diffusion Coefficient by Histogram Analysis

PubMed Central

Song, Yong Sub; Park, Chul-Kee; Yi, Kyung Sik; Lee, Woong Jae; Yun, Tae Jin; Kim, Tae Min; Lee, Se-Hoon; Kim, Ji-Hoon; Sohn, Chul-Ho; Park, Sung-Hye; Kim, Il Han; Jahng, Geon-Ho; Chang, Kee-Hyun

2013-01-01

Objective The purpose of this study was to differentiate true progression from pseudoprogression of glioblastomas treated with concurrent chemoradiotherapy (CCRT) with temozolomide (TMZ) by using histogram analysis of apparent diffusion coefficient (ADC) and normalized cerebral blood volume (nCBV) maps. Materials and Methods Twenty patients with histopathologically proven glioblastoma who had received CCRT with TMZ underwent perfusion-weighted imaging and diffusion-weighted imaging (b = 0, 1000 sec/mm2). The corresponding nCBV and ADC maps for the newly visible, entirely enhancing lesions were calculated after the completion of CCRT with TMZ. Two observers independently measured the histogram parameters of the nCBV and ADC maps. The histogram parameters between the true progression group (n = 10) and the pseudoprogression group (n = 10) were compared by use of an unpaired Student's t test and subsequent multivariable stepwise logistic regression analysis to determine the best predictors for the differential diagnosis between the two groups. Receiver operating characteristic analysis was employed to determine the best cutoff values for the histogram parameters that proved to be significant predictors for differentiating true progression from pseudoprogression. Intraclass correlation coefficient was used to determine the level of inter-observer reliability for the histogram parameters. Results The 5th percentile value (C5) of the cumulative ADC histograms was a significant predictor for the differential diagnosis between true progression and pseudoprogression (p = 0.044 for observer 1; p = 0.011 for observer 2). Optimal cutoff values of 892 × 10-6 mm2/sec for observer 1 and 907 × 10-6 mm2/sec for observer 2 could help differentiate between the two groups with a sensitivity of 90% and 80%, respectively, a specificity of 90% and 80%, respectively, and an area under the curve of 0.880 and 0.840, respectively. There was no other significant differentiating parameter on the nCBV histograms. Inter-observer reliability was excellent or good for all histogram parameters (intraclass correlation coefficient range: 0.70-0.99). Conclusion The C5 of the cumulative ADC histogram can be a promising parameter for the differentiation of true progression from pseudoprogression of newly visible, entirely enhancing lesions after CCRT with TMZ for glioblastomas. PMID:23901325

Design of SERS nanoprobes for Raman imaging: materials, critical factors and architectures.

PubMed

Li, Mingwang; Qiu, Yuanyuan; Fan, Chenchen; Cui, Kai; Zhang, Yongming; Xiao, Zeyu

2018-05-01

Raman imaging yields high specificity and sensitivity when compared to other imaging modalities, mainly due to its fingerprint signature. However, intrinsic Raman signals are weak, thus limiting medical applications of Raman imaging. By adsorbing Raman molecules onto specific nanostructures such as noble metals, Raman signals can be significantly enhanced, termed surface-enhanced Raman scattering (SERS). Recent years have witnessed great interest in the development of SERS nanoprobes for Raman imaging. Rationally designed SERS nanoprobes have greatly enhanced Raman signals by several orders of magnitude, thus showing great potential for biomedical applications. In this review we elaborate on recent progress in design strategies with emphasis on material properties, modifying factors, and structural parameters.

Factors Associated with Enhanced Gross Motor Progress in Children with Cerebral Palsy: A Register-Based Study.

PubMed

Størvold, Gunfrid V; Jahnsen, Reidun B; Evensen, Kari Anne I; Romild, Ulla K; Bratberg, Grete H

2018-05-01

To examine associations between interventions and child characteristics; and enhanced gross motor progress in children with cerebral palsy (CP). Prospective cohort study based on 2048 assessments of 442 children (256 boys, 186 girls) aged 2-12 years registered in the Cerebral Palsy Follow-up Program and the Cerebral Palsy Register of Norway. Gross motor progress estimates were based on repeated measures of reference percentiles for the Gross Motor Function Measure (GMFM-66) in a linear mixed model. Mean follow-up time: 2.9 years. Intensive training was the only intervention factor associated with enhanced gross motor progress (mean 3.3 percentiles, 95% CI: 1.0, 5.5 per period of ≥3 sessions per week and/or participation in an intensive program). Gross motor function was on average 24.2 percentiles (95% CI: 15.2, 33.2) lower in children with intellectual disability compared with others. Except for eating problems (-10.5 percentiles 95% CI: -18.5, -2.4) and ankle contractures by age (-1.9 percentiles 95% CI: -3.6, -0.2) no other factors examined were associated with long-term gross motor progress. Intensive training was associated with enhanced gross motor progress over an average of 2.9 years in children with CP. Intellectual disability was a strong negative prognostic factor. Preventing ankle contractures appears important for gross motor progress.

Measurement of Key Pool BOiling Parameters in nanofluids for Nuclerar Applications

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bang, In C; Buongiorno, Jdacopo; Hu, Lin-wen

Nanofluids, colloidal dispersions of nanoparticles in a base fluid such as water, can afford very significant Critical Heat Flux (CHF) enhancement. Such engineered fluids potentially could be employed in reactors as advanced coolants in safety systems with significant safety and economic advantages. However, a satisfactory explanation of the CHF enhancement mechanism in nanofluids is lacking. To close this gap, we have identified the important boiling parameters to be measured. These are the properties (e.g., density, viscosity, thermal conductivity, specific heat, vaporization enthalpy, surface tension), hydrodynamic parameters (i.e., bubble size, bubble velocity, departure frequency, hot/dry spot dynamics) and surface conditions (i.e.,more » contact angle, nucleation site density). We have also deployed a pool boiling facility in which many such parameters can be measured. The facility is equipped with a thin indium-tin-oxide heater deposited over a sapphire substrate. An infra-red high-speed camera and an optical probe are used to measure the temperature distribution on the heater and the hydrodynamics above the heater, respectively. The first data generated with this facility already provide some clue on the CHF enhancement mechanism in nanofluids. Specifically, the progression to burnout in a pure fluid (ethanol in this case) is characterized by a smoothly-shaped and steadily-expanding hot spot. By contrast, in the ethanol-based nanofluid the hot spot pulsates and the progression to burnout lasts longer, although the nanofluid CHF is higher than the pure fluid CHF. The presence of a nanoparticle deposition layer on the heater surface seems to enhance wettability and aid hot spot dissipation, thus delaying burnout.« less

Exercise Training and Peripheral Arterial Disease

PubMed Central

Haas, Tara L.; Lloyd, Pamela G.; Yang, Hsiao-Tung; Terjung, Ronald L.

2013-01-01

Peripheral arterial disease (PAD) is a common vascular disease that reduces blood flow capacity to the legs of patients. PAD leads to exercise intolerance that can progress in severity to greatly limit mobility, and in advanced cases leads to frank ischemia with pain at rest. It is estimated that 12–15 million people in the United States are diagnosed with PAD, with a much larger population that is undiagnosed. The presence of PAD predicts a 50–1500% increase in morbidity and mortality, depending on severity. Treatment of patients with PAD is limited to modification of cardiovascular disease risk factors, pharmacological intervention, surgery, and exercise therapy. Extended exercise programs that involve walking ~5 times/wk, at a significant intensity that requires frequent rest periods, are most significant. Pre-clinical studies and virtually all clinical trials demonstrate the benefits of exercise therapy, including: improved walking tolerance, modified inflammatory/hemostatic markers, enhanced vasoresponsiveness, adaptations within the limb (angiogenesis, arteriogenesis, mitochondrial synthesis) that enhance oxygen delivery and metabolic responses, potentially delayed progression of the disease, enhanced quality of life indices, and extended longevity. A synthesis is provided as to how these adaptations can develop in the context of our current state of knowledge and events known to be orchestrated by exercise. The benefits are so compelling that exercise prescription should be an essential option presented to patients with PAD in the absence of contraindications. Obviously, selecting for a life style pattern, that includes enhanced physical activity prior to the advance of PAD limitations, is the most desirable and beneficial. PMID:23720270

Clinical usefulness of the ablative margin assessed by magnetic resonance imaging with Gd-EOB-DTPA for radiofrequency ablation of hepatocellular carcinoma.

PubMed

Koda, Masahiko; Tokunaga, Shiho; Okamoto, Toshiaki; Hodozuka, Masanori; Miyoshi, Kennichi; Kishina, Manabu; Fujise, Yuki; Kato, Jun; Matono, Tomomitsu; Sugihara, Takaaki; Oyama, Kenji; Hosho, Keiko; Okano, Jun-ichi; Murawaki, Yoshikazu; Kakite, Suguru; Yamashita, Eijiro

2015-12-01

The aim of this study was to investigate the feasibility of ablative margin (AM) grading by magnetic resonance imaging (MRI) with Gd-EOB-DTPA administered prior to radiofrequency ablation (RFA), and to identify factors for achieving a sufficient AM and predictors for local tumor progression. A total of 124 hepatocellular carcinomas (HCCs) were treated by RFA after Gd-EOB-DTPA administration. MRI and enhanced CT were performed within seven hours and one month after RFA. The AM assessment was categorized using three grades: AM (+), low-intensity area with continuous high-intensity rim; AM zero, low-intensity area with discontinuous high-intensity rim; and AM (-), low-intensity area extends beyond the high-intensity rim. Patients were followed and local tumor progression was observed. AM (+), AM zero, AM (-), and indeterminate were found in 34, 33, 26, and 31 nodules, respectively. The overall agreement rate between MRI and enhanced CT for the diagnosis of AM was 56.8%. The κ coefficient was 0.326 (p<0.001), indicating moderate agreement. Multivariate logistic regression analysis showed that a significant factor for the achievement of AM (+) on MRI was no contiguous vessels. The cumulative local tumor progression rates (0% at 1, 2, and 3 years) in 33 AM (+) nodules were significantly lower than those (3.6%, 11.5%, and 18.3% at 1, 2, and 3 years respectively) in 32 AM zero nodules. A multivariate Cox proportional hazards model identified tumor size as an independent predictor for local tumor progression. Gd-EOB-DTPA-MRI enabled an early assessment of RFA effectiveness in the majority ofHCC nodules. Local tumor progression was not detected in AM (+) nodules during the follow-up. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Hepatic Fibrosis Progression in HIV-Hepatitis C Virus Co-Infection – The Effect of Sex on Risk of Significant Fibrosis Measured by Aspartate-to-Platelet Ratio Index

PubMed Central

Rollet-Kurhajec, Kathleen C.; Moodie, Erica E. M.; Walmsley, Sharon; Cooper, Curtis; Pick, Neora; Klein, Marina B.

2015-01-01

Background In Hepatitis C virus (HCV) mono-infection, male sex is associated with faster liver fibrosis progression but the effects of sex have not been well studied in HIV-HCV co-infected patients. We examined the influence of sex on progression to significant liver fibrosis in HIV-HCV co-infected adults receiving antiretroviral therapy (ART) using the aspartate aminotransferase-to-platelet ratio index (APRI) as a surrogate biomarker of liver fibrosis. Methods We evaluated 308 HIV infected, HCV RNA positive participants of a Canadian multicentre prospective cohort receiving antiretrovirals and without significant liver fibrosis or end-stage liver disease at baseline. We used multivariate discrete-time proportional hazards models to assess the effect of sex on time to significant fibrosis (APRI≥1.5) adjusting for baseline age, alcohol use, cigarette smoking, HCV duration, and APRI and time-updated CD4 count and HIV RNA. Results Overall, 55 (18%) participants developed an APRI ≥ 1.5 over 544 person-years of at-risk follow-up time; 18 (21%) women (incidence rate (IR)=14.0/100 PY; 7.5-20.4) and 37 (17%) men (IR=8.9/100 PY; 6.0-11.8). Women had more favourable profiles with respect to traditional risk factors for liver disease progression (younger, shorter duration of HCV infection and less alcohol use). Despite this, female sex was associated with a greater than two-fold increased risk of fibrosis progression (adjusted hazard rate (HR) =2.23; 1.22-4.08). Conclusions HIV-HCV co-infected women receiving antiretroviral therapy were at significantly greater risk of progressing to liver fibrosis as measured by APRI compared with men. Enhanced efforts to engage and treat co-infected women for HCV are needed. PMID:26090666

[Current Status of Targeted Treatment in Breast Cancer].

PubMed

Seiffert, Katharina; Schmalfeldt, Barbara; Müller, Volkmar

2017-11-01

Within the last years, significant improvements have been achieved in breast cancer treatment, particularly with the development of targeted therapies. Major progress has been made in identifying the drivers malignant growth in oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of the cyclin-dependent kinases CDK4 and CDK6 like palbociclib and inhibitors of mTOR substantially improve progression-free survival. For patients with HER2-positive disease the addition of Pertuzumab to Trastuzumab in combination with chemotherapy has been a significant improvement in anti-HER2 therapy in early as well as metastatic breast cancer. Evidence-based further line therapy options in the metastatic setting include T-DM1 and in later lines Lapatinib. For triple negative disease the angiogenesis inhibitor Bevacizumab is approved, which increases progression free survival. Immune checkpoint inhibitors, PARP-inhibitors or anti-androgens represent promising strategies, all of which are currently being evaluated in clinical trials. The development of predictive biomarkers to guide targeted therapies is still the subject of research. © Georg Thieme Verlag KG Stuttgart · New York.

CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

PubMed Central

Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

2014-01-01

The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

Research Progress in Carbon Dioxide Storage and Enhanced Oil Recovery

NASA Astrophysics Data System (ADS)

Wang, Keliang; Wang, Gang; Lu, Chunjing

2018-02-01

With the rapid development of global economy, human beings have become highly dependent upon fossil fuel such as coal and petroleum. Much fossil fuel is consumed in industrial production and human life. As a result, carbon dioxide emissions have been increasing, and the greenhouse effects thereby generated are posing serious threats to environment of the earth. These years, increasing average global temperature, frequent extreme weather events and climatic changes cause material disasters to the world. After scientists’ long-term research, ample evidences have proven that emissions of greenhouse gas like carbon dioxide have brought about tremendous changes to global climate. To really reduce carbon dioxide emissions, governments of different countries and international organizations have invested much money and human resources in performing research related to carbon dioxide emissions. Manual underground carbon dioxide storage and carbon dioxide-enhanced oil recovery are schemes with great potential and prospect for reducing carbon dioxide emissions. Compared with other schemes for reducing carbon dioxide emissions, aforementioned two schemes exhibit high storage capacity and yield considerable economic benefits, so they have become research focuses for reducing carbon dioxide emissions. This paper introduces the research progress in underground carbon dioxide storage and enhanced oil recovery, pointing out the significance and necessity of carbon dioxide-driven enhanced oil recovery.

Glycogen Synthase Kinase-3 and Mammalian Target of Rapamycin Pathways Contribute to DNA Synthesis, Cell Cycle Progression, and Proliferation in Human Islets

PubMed Central

Liu, Hui; Remedi, Maria S.; Pappan, Kirk L.; Kwon, Guim; Rohatgi, Nidhi; Marshall, Connie A.; McDaniel, Michael L.

2009-01-01

OBJECTIVE—Our previous studies demonstrated that nutrient regulation of mammalian target of rapamycin (mTOR) signaling promotes regenerative processes in rodent islets but rarely in human islets. Our objective was to extend these findings by using therapeutic agents to determine whether the regulation of glycogen synthase kinase-3 (GSK-3)/β-catenin and mTOR signaling represent key components necessary for effecting a positive impact on human β-cell mass relevant to type 1 and 2 diabetes. RESEARCH DESIGN AND METHODS—Primary adult human and rat islets were treated with the GSK-3 inhibitors, LiCl and the highly potent 1-azakenpaullone (1-Akp), and with nutrients. DNA synthesis, cell cycle progression, and proliferation of β-cells were assessed. Measurement of insulin secretion and content and Western blot analysis of GSK-3 and mTOR signaling components were performed. RESULTS—Human islets treated for 4 days with LiCl or 1-Akp exhibited significant increases in DNA synthesis, cell cycle progression, and proliferation of β-cells that displayed varying degrees of sensitivity to rapamycin. Intermediate glucose (8 mmol/l) produced a striking degree of synergism in combination with GSK-3 inhibition to enhance bromodeoxyuridine (BrdU) incorporation and Ki-67 expression in human β-cells. Nuclear translocation of β-catenin responsible for cell proliferation was found to be particularly sensitive to rapamycin. CONCLUSIONS—A combination of GSK-3 inhibition and nutrient activation of mTOR contributes to enhanced DNA synthesis, cell cycle progression, and proliferation of human β-cells. Identification of therapeutic agents that appropriately regulate GSK-3 and mTOR signaling may provide a feasible and available approach to enhance human islet growth and proliferation. PMID:19073772

Patterns of Failure After Concurrent Bevacizumab and Hypofractionated Stereotactic Radiation Therapy for Recurrent High-Grade Glioma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shapiro, Lauren Q.; Beal, Kathryn, E-mail: bealk@mskcc.org; Goenka, Anuj

2013-03-01

Purpose: Concurrent bevacizumab with hypofractionated stereotactic radiation therapy (HSRT) is safe and effective for the treatment of recurrent high-grade gliomas (HGG). The objective of this study was to characterize the patterns of failure after this treatment regimen. Methods and Materials: Twenty-four patients with recurrent enhancing HGG were previously treated on an institutional review board-approved protocol of concurrent bevacizumab and reirradiation. Patients received 30 Gy in 5 fractions to the recurrent tumor with HSRT. Brain magnetic resonance imaging (MRI) was performed every 2 cycles, and bevacizumab was continued until clinical or radiographic tumor progression according to the criteria of Macdonald etmore » al. MRI at the time of progression was fused to the HSRT treatment plan, and the location of recurrence was classified on the basis of volume within the 95% isodose line. Outcomes based on patient characteristics, tumor grade, recurrence pattern, and best response to treatment were analyzed by the Kaplan-Meier method. Results: Twenty-two patients experienced either clinical or radiographic progression. Recurrent tumor was enhancing in 15 (71.4%) and nonenhancing in 6 (28.6%) patients. Eleven patients (52.4%) had recurrence within the radiation field, 5 patients (23.8%) had marginal recurrence, and 5 patients had recurrence outside the radiation field. Pattern of enhancement and location of failure did not correlate with overall survival or progression-free survival. Radiographic response was the only variable to significantly correlate with progression-free survival. Conclusions: Despite the promising initial response seen with the addition of HSRT to bevacizumab as salvage treatment for recurrent HGG, approximately half of patients ultimately still experience failure within the radiation field. The rate of local failure with the addition of HSRT seems to be lower than that seen with bevacizumab alone in the salvage setting. Our data underscore the radioresistance of HGG and the need for better salvage treatments.« less

Type III TGF-β Receptor Enhances Colon Cancer Cell Migration and Anchorage-Independent Growth12

PubMed Central

Gatza, Catherine E; Holtzhausen, Alisha; Kirkbride, Kellye C; Morton, Allyson; Gatza, Michael L; Datto, Michael B; Blobe, Gerard C

2011-01-01

The type III TGF-β receptor (TβRIII or betagylcan) is a TGF-β superfamily coreceptor with emerging roles in regulating TGF-β superfamily signaling and cancer progression. Alterations in TGF-β superfamily signaling are common in colon cancer; however, the role of TβRIII has not been examined. Although TβRIII expression is frequently lost at the message and protein level in human cancers and suppresses cancer progression in these contexts, here we demonstrate that, in colon cancer, TβRIII messenger RNA expression is not significantly altered and TβRIII expression is more frequently increased at the protein level, suggesting a distinct role for TβRIII in colon cancer. Increasing TβRIII expression in colon cancer model systems enhanced ligand-mediated phosphorylation of p38 and the Smad proteins, while switching TGF-β and BMP-2 from inhibitors to stimulators of colon cancer cell proliferation, inhibiting ligand-induced p21 and p27 expression. In addition, increasing TβRIII expression increased ligand-stimulated anchorage-independent growth, a resistance to ligand- and chemotherapy-induced apoptosis, cell migration and modestly increased tumorigenicity in vivo. In a reciprocal manner, silencing endogenous TβRIII expression decreased colon cancer cell migration. These data support a model whereby TβRIII mediates TGF-β superfamily ligand-induced colon cancer progression and support a context-dependent role for TβRIII in regulating cancer progression. PMID:21847367

A Functional Variant of SMAD4 Enhances Thoracic Aortic Aneurysm and Dissection Risk through Promoting Smooth Muscle Cell Apoptosis and Proteoglycan Degradation.

PubMed

Wang, Ying; Huang, Hao-Yue; Bian, Guang-Liang; Yu, Yun-Sheng; Ye, Wen-Xue; Hua, Fei; Chen, Yi-Huan; Shen, Zhen-Ya

2017-07-01

Recent studies indicate important roles for SMAD4 in SMCs proliferation, extracellular matrix maintenance, and blood vessel remodeling. However, the genetic effects of SMAD4 in the pathogenesis of thoracic aortic aneurysm and dissection (TAAD) are still largely unknown. Here we identified a functional variant of SMAD4 which might be involved in the pathological progression of TAAD. Five tagging SNPs of SMAD4 were genotyped in 202 TAAD cases and 400 controls using MALDI-TOF. rs12455792 CT or TT variant genotypes was associated with an significantly elevated TAAD risk (adjusted OR=1.58, 95%CI=1.09-2.30) under a dominant genetic model. It was located in the 5'UTR and predicted to influence transcription activity and RNA folding of SMAD4. In luciferase reporter assay, rs12455792 T allele markedly decreased luciferase activities. Accordingly, SMAD4 expression in tissues was lower in patients with CT or TT genotypes, compared with CC. Movat's pentachrome showed that rs12455792 T allele enhanced SMCs loss and fibers accumulation. With angiotensin II induction, rate of Apoptotic SMCs was significantly higher while SMAD4 silenced. Moreover, rs12455792 T allele also increased Versican degradation via ADAMTS-4. In conclusion, this variant might promote SMCs apoptosis and proteoglycans degradation, and further facilitate the progress of TAAD. Our findings identified rs12455792 as a predictor for progression of vascular media pathological changes related thoracic aortic disorders. Copyright © 2017. Published by Elsevier B.V.

The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

PubMed

Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

2012-01-05

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

Facilities Performance Indicators Report 2010-11: Tracking Your Facilities Vital Signs

ERIC Educational Resources Information Center

APPA: Association of Higher Education Facilities Officers, 2012

2012-01-01

APPA's Information and Research Committee's goal for this year was to enhance the survey and report tools by making them both more navigable, user friendly, and accurate. Significant progress has been made with all of these initiatives. APPA also automated many of the internal processes for the survey and report, which resulted in a…

Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment.

PubMed

Liu, Hao-Li; Hua, Mu-Yi; Chen, Pin-Yuan; Chu, Po-Chun; Pan, Chia-Hsin; Yang, Hung-Wei; Huang, Chiung-Yin; Wang, Jiun-Jie; Yen, Tzu-Chen; Wei, Kuo-Chen

2010-05-01

To demonstrate the feasibility of using focused ultrasound to enhance delivery of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to glioblastomas in rats with induced tumors and determine if such an approach increases treatment efficacy. All animal experiments were approved by the animal committee and adhered to the experimental animal care guidelines. A 400-kHz focused ultrasound generator was used to transcranially disrupt the blood-brain barrier (BBB) in rat brains by delivering burst-tone ultrasound energy in the presence of microbubbles. The process was monitored in vivo by using magnetic resonance (MR) imaging. Cultured C6 glioma cells implanted in Sprague-Dawley rats were used as the tumor model. BCNU (13.5 mg/kg) was administered intravenously and its concentration in brains was quantified by using high-performance liquid chromatography. MR imaging was used to evaluate the effect of treatments longitudinally, including analysis of tumor progression and animal survival, and brain tissues were histologically examined. Methods including the two-tailed unpaired t test and the Mantel-Cox test were used for statistical analyses, with a significance level of .05. Focused ultrasound significantly enhanced the penetration of BCNU through the BBB in normal (by 340%) and tumor-implanted (by 202%) brains without causing hemorrhaging. Treatment of tumor-implanted rats with focused ultrasound alone had no beneficial effect on tumor progression or on animal survival up to 60 days. Administration of BCNU only transiently controlled tumor progression; nevertheless, relative to untreated controls, animal survival was improved by treatment with BCNU alone (increase in median survival time [IST(median)], 15.7%, P = .023). Treatment with focused ultrasound before BCNU administration controlled tumor progression (day 31: 0.05 cm(3) + or - 0.1 [standard deviation] vs 0.28 cm(3) + or - 0.1) and improved animal survival relative to untreated controls (IST(median), 85.9%, P = .0015). This study demonstrates a means of increasing localized chemotherapeutic drug delivery for brain tumor treatment and strongly supports the feasibility of this treatment in a clinical setting.

Oxidative stress induced mechanisms in the progression of periodontal diseases and cancer: a common approach to redox homeostasis?

PubMed

Soory, Mena

2010-04-26

There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers and periodontal diseases of the supporting structures of the teeth. Enhanced lipid peroxidation, raised levels of TBARS and the oxidative stress marker malondealdehyde have been detected in breast cancer with reduced antioxidant capacity, also characteristic of periodontal diseases. Antioxidants could overcome this deficit and attenuate disease progression by down regulating glutathione detoxification/redox buffering system and inhibiting key transcription factors. Periodontal disease may be a critical marker of a susceptible immune system, or initiate cancer risk with a pro-oxidant inflammatory profile.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Chuanyi; Shen, Liangfang, E-mail: lfshen2008@163.com; Mao, Lei

MicroRNAs (miRNAs) are involved in the cervical carcinogenesis and progression. In this study, we investigated the role of miR-92a in progression and invasion of cervical cancer. MiR-92a was significantly upregulated in cervical cancer tissues and cell lines. Overexpression of miR-92a led to remarkably enhanced proliferation by promoting cell cycle transition from G1 to S phase and significantly enhanced invasion of cervical cancer cells, while its knockdown significantly reversed these cellular events. Bioinformatics analysis suggested F-box and WD repeat domain-containing 7 (FBXW7) as a novel target of miR-92a, and miR-92a suppressed the expression level of FBXW7 mRNA by direct binding tomore » its 3′-untranslated region (3′UTR). Expression of miR-92a was negatively correlated with FBXW7 in cervical cancer tissues. Furthermore, Silencing of FBXW7 counteracted the effects of miR-92a suppression, while its overexpression reversed oncogenic effects of miR-92a. Together, these findings indicate that miR-92a acts as an onco-miRNA and may contribute to the progression and invasion of cervical cancer, suggesting miR-92a as a potential novel diagnostic and therapeutic target of cervical cancer. - Highlights: • miR-92a is elevated in cervical cancer tissues and cell lines. • miR-92a promotes cervical cancer cell proliferation, cell cycle transition from G1 to S phase and invasion. • FBXW7 is a direct target of miR-92a. • FBXW7 counteracts the oncogenic effects of miR-92a on cervical cancer cells.« less

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma.

PubMed

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-05-07

To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test ( P = 0.002). The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs.

Rate of local tumor progression following radiofrequency ablation of pathologically early hepatocellular carcinoma

PubMed Central

Hao, Yoshiteru; Numata, Kazushi; Ishii, Tomohiro; Fukuda, Hiroyuki; Maeda, Shin; Nakano, Masayuki; Tanaka, Katsuaki

2017-01-01

AIM To evaluate whether pathologically early hepatocellular carcinoma (HCC) exhibited local tumor progression after radiofrequency ablation (RFA) less often than typical HCC. METHODS Fifty pathologically early HCCs [tumor diameter (mm): mean, 15.8; range, 10-23; follow-up days after RFA: median, 1213; range, 216-2137] and 187 typical HCCs [tumor diameter (mm): mean, 15.6; range, 6-30; follow-up days after RFA: median, 1116; range, 190-2328] were enrolled in this retrospective study. The presence of stromal invasion (namely, tumor cell invasion into the intratumoral portal tracts) was considered to be the most important pathologic finding for the diagnosis of early HCCs. Typical HCC was defined as the presence of a hyper-vascular lesion accompanied by delayed washout using contrast-enhanced computed tomography or contrast-enhanced magnetic resonance imaging. Follow-up examinations were performed at 3-mo intervals to monitor for signs of local tumor progression. The local tumor progression rates of pathologically early HCCs and typical HCCs were then determined using the Kaplan-Meier method. RESULTS During the follow-up period for the 50 pathologically early HCCs, 49 (98%) of the nodules did not exhibit local tumor progression. However, 1 nodule (2%) was associated with a local tumor progression found 636 d after RFA. For the 187 typical HCCs, 46 (24.6%) of the nodules exhibited local recurrence after RFA. The follow-up period until the local tumor progression of typical HCC was a median of 605 d, ranging from 181 to 1741 d. Among the cases with typical HCCs, local tumor progression had occurred in 7.0% (7/187), 16.0% (30/187), 21.9% (41/187) and 24.6% (46/187) of the cases at 1, 2, 3 and 4 years, respectively. Pathologically early HCC was statistically associated with a lower rate of local tumor progression, compared with typical HCC, when evaluated using a log-rank test (P = 0.002). CONCLUSION The rate of local tumor progression for pathologically early HCCs after RFA was significantly lower than that for typical HCCs. PMID:28533668

Metamaterials Application in Sensing

PubMed Central

Chen, Tao; Li, Suyan; Sun, Hui

2012-01-01

Metamaterials are artificial media structured on a size scale smaller than wavelength of external stimuli, and they can exhibit a strong localization and enhancement of fields, which may provide novel tools to significantly enhance the sensitivity and resolution of sensors, and open new degrees of freedom in sensing design aspect. This paper mainly presents the recent progress concerning metamaterials-based sensing, and detailedly reviews the principle, detecting process and sensitivity of three distinct types of sensors based on metamaterials, as well as their challenges and prospects. Moreover, the design guidelines for each sensor and its performance are compared and summarized. PMID:22736975

Identifying the association between contrast enhancement pattern, surgical resection, and prognosis in anaplastic glioma patients.

PubMed

Wang, Yinyan; Wang, Kai; Wang, Jiangfei; Li, Shaowu; Ma, Jun; Dai, Jianping; Jiang, Tao

2016-04-01

Contrast enhancement observable on magnetic resonance (MR) images reflects the destructive features of malignant gliomas. This study aimed to investigate the relationship between radiologic patterns of tumor enhancement, extent of resection, and prognosis in patients with anaplastic gliomas (AGs). Clinical data from 268 patients with histologically confirmed AGs were retrospectively analyzed. Contrast enhancement patterns were classified based on preoperative T1-contrast MR images. Univariate and multivariate analyses were performed to evaluate the prognostic value of MR enhancement patterns on progression-free survival (PFS) and overall survival (OS). The pattern of tumor contrast enhancement was associated with the extent of surgical resection in AGs. A gross total resection was more likely to be achieved for AGs with focal enhancement than those with diffuse (p = 0.001) or ring-like (p = 0.024) enhancement. Additionally, patients with focal-enhanced AGs had a significantly longer PFS and OS than those with diffuse (log-rank, p = 0.025 and p = 0.031, respectively) or ring-like (log-rank, p = 0.008 and p = 0.011, respectively) enhanced AGs. Furthermore, multivariate analysis identified the pattern of tumor enhancement as a significant predictor of PFS (p = 0.016, hazard ratio [HR] = 1.485) and OS (p = 0.030, HR = 1.446). Our results suggested that the contrast enhancement pattern on preoperative MR images was associated with the extent of resection and predictive of survival outcomes in AG patients.

Metamorphic III–V Solar Cells: Recent Progress and Potential

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, Ivan; France, Ryan M.; Geisz, John F.

Inverted metamorphic multijunction solar cells have been demonstrated to be a pathway to achieve the highest photovoltaic (PV) conversion efficiencies. Attaining high-quality lattice-mismatched (metamorphic) semiconductor devices is challenging. However, recent improvements to compositionally graded buffer epitaxy and junction structures have led to the achievement of high-quality metamorphic solar cells exhibiting internal luminescence efficiencies over 90%. For this high material quality, photon recycling is significant, and therefore, the optical environment of the solar cell becomes important. In this paper, we first present recent progress and performance results for 1- and 0.7-eV GaInAs solar cells grown on GaAs substrates. Then, an electroopticalmore » model is used to assess the potential performance improvements in current metamorphic solar cells under different realizable design scenarios. The results show that the quality of 1-eV subcells is such that further improving its electronic quality does not produce significant Voc increases in the four-junction inverted metamorphic subcells, unless a back reflector is used to enhance photon recycling, which would significantly complicate the structure. Conversely, improving the electronic quality of the 0.7-eV subcell would lead to significant Voc boosts, driving the progress of four-junction inverted metamorphic solar cells.« less

NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.

PubMed

Rodrigues, Paulo; Patel, Saroor A; Harewood, Louise; Olan, Ioana; Vojtasova, Erika; Syafruddin, Saiful E; Zaini, M Nazhif; Richardson, Emma K; Burge, Johanna; Warren, Anne Y; Stewart, Grant D; Saeb-Parsy, Kourosh; Samarajiwa, Shamith A; Vanharanta, Sakari

2018-06-06

Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states. SIGNIFICANCE: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 1-16. ©2018 AACR. ©2018 American Association for Cancer Research.

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma.

PubMed

Zou, Shitao; Shang, Zeng-Fu; Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

2016-05-31

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC.

DNA polymerase iota (Pol ι) promotes invasion and metastasis of esophageal squamous cell carcinoma

PubMed Central

Liu, Biao; Zhang, Shuyu; Wu, Jinchang; Huang, Min; Ding, Wei-Qun; Zhou, Jundong

2016-01-01

DNA polymerase iota (Pol ι) is an error-prone DNA polymerase involved in translesion DNA synthesis (TLS) that contributes to the accumulation of DNA mutations. We recently showed that Pol ι is overexpressed in human esophageal squamous cell cancer (ESCC) tissues which promotes ESCC' progression. The present study was aimed at investigating the molecular mechanisms by which Pol ι enhances the invasiveness and metastasis of ESCC cells. We found that the expression of Pol ι is significantly higher in ESCCs with lymph node metastasis compared to those without lymph node metastasis. Kaplan-Meier analysis revealed an inverse correlation between Pol ι expression and patient prognosis. The expression levels of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9), two essential regulators of cells' invasiveness, were positively associated with Pol ι expression in ESCC tissues. Ectopic expression of Pol ι enhanced the motility and invasiveness of ESCC cells as evaluated by wound-healing and transwell assays, respectively. A xenograft nude mouse model showed that Pol ι promotes the colonization of ESCC cells in the liver, lung and kidney. Signaling pathway analysis identified the JNK-AP-1 cascade as a mediator of the Pol ι-induced increase in the expression of MMP-2/9 and enhancement of ESCC progression. These data demonstrate the underlying mechanism by which Pol ι promotes ESCC progression, suggesting that Pol ι is a potential novel prognostic biomarker and therapeutic target for ESCC. PMID:27057634

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

PubMed Central

Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

[Mathematic Model for Prediction of Liver Fibrosis Progression Rate in Patients with Chronic Hepatitis C Based on Combination of Genomic Markers].

PubMed

Samokhodskaia, L M; Starostina, E E; Yarovaya, E B; Krasnova, T N; Mukhin, N A; Tkachuk, V A; Sadovnichy, V A

2015-01-01

To evaluate clinical significance of different combinations of gene polymorphisms IL-1b, IL-6, IL-10, TNF, HFE, TGF-b, ATR1, N0S3894, CYBA, AGT, MTHFR, FII, FV, FVII, FXIII, ITGA2, ITGB3, FBG, PAI and their prognostic value for prediction of liver fibrosis progression rate in patients with chronic hepatitis C (CHC). 118 patients with CHC were divided into "fast" and "slow" (fibrosis rate progression ≥ 0.13 and < 0.13 fibrosis units/yr; n = 64 and n = 54) fibrosis groups. Gene polymorphisms were determined. Statistical analysis was performed using Statistica 10. A allele (p = 0.012) and genotype AA (p = 0.024) of AGT G-6T gene, as well as T allele (p = 0.013) and MT+TT genotypes (p = 0.005) of AGT 235 M/T gene were significantly more common in "fast fibrosers" than in "slow fibrosers". Patients with genotype TT of CYBA 242 C/T had a higher fibrosis progression rate than patients with CC+CT genotype (p = 0.02). Our analysis showed a protective effect of TTgenotype of ITGA2 807 C/T on fibrosis progression rate (p = 0.03). There was a trend (p < 0.15) to higher fibrosis progression rate in patients with mutant alleles and genotypes of TGFb +915 G/C, FXIII 103 G/T, PAI-675 5G/4G genes. Other gene polymorphisms were not associated with enhanced liver fibrosis. To build a mathematical modelfor prediction of liverfibrosis progression rate we performed coding with scores for genotypes and virus genotype. Total score correlated with the fibrosis progression rate (R = 0.39, p = 0.000). Determination of genetic profile of the patient and virus genotype allows to predict the course of CHC.

Software for enhanced video capsule endoscopy: challenges for essential progress.

PubMed

Iakovidis, Dimitris K; Koulaouzidis, Anastasios

2015-03-01

Video capsule endoscopy (VCE) has revolutionized the diagnostic work-up in the field of small bowel diseases. Furthermore, VCE has the potential to become the leading screening technique for the entire gastrointestinal tract. Computational methods that can be implemented in software can enhance the diagnostic yield of VCE both in terms of efficiency and diagnostic accuracy. Since the appearance of the first capsule endoscope in clinical practice in 2001, information technology (IT) research groups have proposed a variety of such methods, including algorithms for detecting haemorrhage and lesions, reducing the reviewing time, localizing the capsule or lesion, assessing intestinal motility, enhancing the video quality and managing the data. Even though research is prolific (as measured by publication activity), the progress made during the past 5 years can only be considered as marginal with respect to clinically significant outcomes. One thing is clear-parallel pathways of medical and IT scientists exist, each publishing in their own area, but where do these research pathways meet? Could the proposed IT plans have any clinical effect and do clinicians really understand the limitations of VCE software? In this Review, we present an in-depth critical analysis that aims to inspire and align the agendas of the two scientific groups.

Polycrystalline Si nanoparticles and their strong aging enhancement of blue photoluminescence

NASA Astrophysics Data System (ADS)

Yang, Shikuan; Cai, Weiping; Zeng, Haibo; Li, Zhigang

2008-07-01

Nearly spherical polycrystalline Si nanoparticles with 20 nm diameter were fabricated based on laser ablation of silicon wafer immersed in sodium dodecyl sulfate aqueous solution. Such Si nanoparticles consist of disordered areas and ultrafine grains of 3 nm in mean size and exhibit significant photoluminescence in blue region. Importantly, aging at ambient air leads to continuing enhancement of the emission (more than 130 times higher in 16 weeks) showing stable and strong blue emission. This aging enhancement is attributed to progressive passivation of nonradiative Pb centers corresponding to silicon dangling bonds on the particles' surface. This study could be helpful in pushing Si into optoelectronic field and Si-based full color display, biomedical tagging, and flash memories.

Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaid, Mudit; Singh, Tripti; Prasad, Ram

Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180 mJ/cm{sup 2}) three times a week for 24 weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P < 0.01–0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression ofmore » UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E{sub 2} (P < 0.01), and PGE{sub 2} receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P < 0.01), interleukin (IL)-1β (P < 0.01) and IL-6 (P < 0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser{sup 473} in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors. - Highlights: • Consumption of high-fat diet increases UVB-induced skin tumor development in mice. • Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma. • Intake of high-fat diet enhances inflammation in UV-exposed skin • Regular consumption of low-fat diet may inhibit the risk of photocarcinogenesis.« less

Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

PubMed

Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

2010-12-01

There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

Microalgal hydrogen production - A review.

PubMed

Khetkorn, Wanthanee; Rastogi, Rajesh P; Incharoensakdi, Aran; Lindblad, Peter; Madamwar, Datta; Pandey, Ashok; Larroche, Christian

2017-11-01

Bio-hydrogen from microalgae including cyanobacteria has attracted commercial awareness due to its potential as an alternative, reliable and renewable energy source. Photosynthetic hydrogen production from microalgae can be interesting and promising options for clean energy. Advances in hydrogen-fuel-cell technology may attest an eco-friendly way of biofuel production, since, the use of H 2 to generate electricity releases only water as a by-product. Progress in genetic/metabolic engineering may significantly enhance the photobiological hydrogen production from microalgae. Manipulation of competing metabolic pathways by modulating the certain key enzymes such as hydrogenase and nitrogenase may enhance the evolution of H 2 from photoautotrophic cells. Moreover, biological H 2 production at low operating costs is requisite for economic viability. Several photobioreactors have been developed for large-scale biomass and hydrogen production. This review highlights the recent technological progress, enzymes involved and genetic as well as metabolic engineering approaches towards sustainable hydrogen production from microalgae. Copyright © 2017 Elsevier Ltd. All rights reserved.

Nutrient enrichment enhances black band disease progression in corals

NASA Astrophysics Data System (ADS)

Voss, Joshua D.; Richardson, Laurie L.

2006-11-01

Infectious diseases are recognized as significant contributors to the dramatic loss of corals observed worldwide. However, the causes of increased coral disease prevalence and severity are not well understood. One potential factor is elevated nutrient concentration related to localized anthropogenic activities such as inadequate waste water treatment or terrestrial runoff. In this study the effect of nutrient enrichment on the progression of black band disease (BBD) was investigated using both in situ and laboratory experiments. Experimental increases in localized nutrient availability using commercial time release fertilizer in situ resulted in doubling of BBD progression and coral tissue loss in the common reef framework coral Siderastrea siderea. Laboratory experiments in which artificially infected S. siderea colonies were exposed to increased nitrate concentrations (up to 3 μM) demonstrated similar increases in BBD progression. These findings provide evidence that the impacts of this disease on coral populations are exacerbated by nutrient enrichment and that management to curtail excess nutrient loading may be important for reducing coral cover loss due to BBD.

High-Fat-Diet Intake Enhances Cerebral Amyloid Angiopathy and Cognitive Impairment in a Mouse Model of Alzheimer's Disease, Independently of Metabolic Disorders.

PubMed

Lin, Bowen; Hasegawa, Yu; Takane, Koki; Koibuchi, Nobutaka; Cao, Cheng; Kim-Mitsuyama, Shokei

2016-06-13

The high-fat Western diet is postulated to be associated with the onset and progression of Alzheimer's disease (AD). However, the role of high-fat-diet consumption in AD pathology is unknown. This study was undertaken to examine the role of high-fat-diet intake in AD. 5XFAD mice, a useful mouse model of AD, and control wild-type mice were fed (1) high-fat diet or (2) control diet for 10 weeks. The effects on cerebral AD pathology, cognitive function, and metabolic parameters were compared between each group of mice. High-fat diet significantly enhanced cerebrovascular β-amyloid (Aβ) deposition (P<0.05) and impaired cognitive function (P<0.05) in 5XFAD mice, but not in wild-type mice. High-fat diet enhanced hippocampal oxidative stress (P<0.05) and NADPH oxidase subunits, gp91(phox) (P<0.01) and p22(phox) (P<0.01) in 5XFAD mice, but not in wild-type mice. Furthermore, high-fat diet reduced cerebral occludin (P<0.05) in 5XFAD mice, but not in wild-type mice. Thus, 5XFAD mice exhibited greater susceptibility to high-fat diet than wild-type mice regarding cerebrovascular injury and cognitive impairment. On the other hand, 5XFAD mice fed high-fat diet exhibited much less increase in body weight, white adipose tissue weight, and adipocyte size than their wild-type counterparts. High-fat diet significantly impaired glucose tolerance in wild-type mice but not in 5XFAD mice. Thus, 5XFAD mice had much less susceptibility to high-fat-diet-induced metabolic disorders than wild-type mice. High-fat diet, independently of metabolic disorders, significantly promotes the progression of AD-like pathology through enhancement of cerebral amyloid angiopathy and oxidative stress. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

The Role ERG and CXCR4 in Prostate Cancer Progression

DTIC Science & Technology

2011-06-01

axis functions in PC progression to enhance invasion and metastasis. To address the regulation of CXCR4 expression, we identified several putative ERG...interaction between ERG factor and CXCR4 gene promoter and link these activities with TMPRSS2-ERG translocations and enhanced metastasis of tumor cells via...and increased VCaP nuclear extract protein in assay enhanced the intensity of bands (Figure 1D). Inclusion of anti-ERG antibodies super shifted

Photokinetic Drug Delivery: Light-Enhanced Permeation in an In Vitro Eye Model.

PubMed

Godley, Bernard F; Kraft, Edward R; Giannos, Steven A; Zhao, Zhen-Yang; Haag, Anthony M; Wen, Julie W

2015-12-01

To investigate light-enhanced molecular movement as a potential technology for drug delivery. To do this, we developed an in vitro eye model while representing similar concentration gradient conditions and compositions found in the eye. The eye model unit was fabricated by inserting a cross-linked type I collagen membrane in a spectrophotometer cuvette with 1% hyaluronic acid as the drug recipient medium. Photokinetic delivery was studied by illuminating 1 mg/mL methotrexate (MTX) placed in the drug donor compartment on top of the membrane, with noncoherent 450 nm light at 8.2 mW from an LED source pulsed at 25 cycles per second, placed in contact with the solution. A modified UV-visual spectrophotometer was employed to rapidly determine the concentration of MTX, at progressive 1 mm distances away from the membrane, within the viscous recipient medium of the model eye after 1 h. A defined, progressive concentration gradient was observed within the nonagitated drug recipient media, diminishing with greater distances from the membrane. Transport of MTX through the membrane was significantly enhanced (ranging from 2 to 3 times, P < 0.05 to P ≤ 0.001) by photokinetic methods compared with control conditions by determining drug concentrations at 4 defined distances from the membrane. According to scanning electron microscopy images, no structural damage or shunts were created on the surface of the cross-linked gelatin membrane. The application of pulsed noncoherent visible light significantly enhances the permeation of MTX through a cross-linked collagen membrane and hyaluronic acid recipient medium without causing structural damage to the membrane.

Periodic array-based substrates for surface-enhanced infrared spectroscopy

NASA Astrophysics Data System (ADS)

Mayerhöfer, Thomas G.; Popp, Jürgen

2018-01-01

At the beginning of the 1980s, the first reports of surface-enhanced infrared spectroscopy (SEIRS) surfaced. Probably due to signal-enhancement factors of only 101 to 103, which are modest compared to those of surface-enhanced Raman spectroscopy (SERS), SEIRS did not reach the same significance up to date. However, taking the compared to Raman scattering much larger cross-sections of infrared absorptions and the enhancement factors together, SEIRS reaches about the same sensitivity for molecular species on a surface in terms of the cross-sections as SERS and, due to the complementary nature of both techniques, can valuably augment information gained by SERS. For the first 20 years since its discovery, SEIRS relied completely on metal island films, fabricated by either vapor or electrochemical deposition. The resulting films showed a strong variance concerning their structure, which was essentially random. Therefore, the increase in the corresponding signal-enhancement factors of these structures stagnated in the last years. In the very same years, however, the development of periodic array-based substrates helped SEIRS to gather momentum. This development was supported by technological progress concerning electromagnetic field solvers, which help to understand plasmonic properties and allow targeted design. In addition, the strong progress concerning modern fabrication methods allowed to implement these designs into practice. The aim of this contribution is to critically review the development of these engineered surfaces for SEIRS, to compare the different approaches with regard to their performance where possible, and report further gain of knowledge around and in relation to these structures.

Biologically Enhanced Carbon Sequestration: Research Needs and Opportunities

DOE Office of Scientific and Technical Information (OSTI.GOV)

Oldenburg, Curtis; Oldenburg, Curtis M.; Torn, Margaret S.

2008-03-21

Fossil fuel combustion, deforestation, and biomass burning are the dominant contributors to increasing atmospheric carbon dioxide (CO{sub 2}) concentrations and global warming. Many approaches to mitigating CO{sub 2} emissions are being pursued, and among the most promising are terrestrial and geologic carbon sequestration. Recent advances in ecology and microbial biology offer promising new possibilities for enhancing terrestrial and geologic carbon sequestration. A workshop was held October 29, 2007, at Lawrence Berkeley National Laboratory (LBNL) on Biologically Enhanced Carbon Sequestration (BECS). The workshop participants (approximately 30 scientists from California, Illinois, Oregon, Montana, and New Mexico) developed a prioritized list of researchmore » needed to make progress in the development of biological enhancements to improve terrestrial and geologic carbon sequestration. The workshop participants also identified a number of areas of supporting science that are critical to making progress in the fundamental research areas. The purpose of this position paper is to summarize and elaborate upon the findings of the workshop. The paper considers terrestrial and geologic carbon sequestration separately. First, we present a summary in outline form of the research roadmaps for terrestrial and geologic BECS. This outline is elaborated upon in the narrative sections that follow. The narrative sections start with the focused research priorities in each area followed by critical supporting science for biological enhancements as prioritized during the workshop. Finally, Table 1 summarizes the potential significance or 'materiality' of advances in these areas for reducing net greenhouse gas emissions.« less

Oral administration of Pantoea agglomerans-derived lipopolysaccharide prevents metabolic dysfunction and Alzheimer's disease-related memory loss in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet.

PubMed

Kobayashi, Yutaro; Inagawa, Hiroyuki; Kohchi, Chie; Kazumura, Kimiko; Tsuchiya, Hiroshi; Miwa, Toshiyuki; Okazaki, Katsuichiro; Soma, Gen-Ichiro

2018-01-01

The pathogenesis of Alzheimer's disease (AD) remains unclear, but an imbalance between the production and clearance of amyloid-β (Aβ) peptides is known to play a critical role in AD progression. A promising preventative approach is to enhance the normal Aβ clearance activity of brain phagocytes such as microglia. In mice, the intraperitoneal injection of Toll-like receptor 4 agonist was shown to enhance Aβ clearance and exhibit a preventative effect on AD-related pathology. Our previous clinical study demonstrated that orally administered Pantoea agglomerans-derived lipopolysaccharide (LPSp) exhibited an LDL (low-density lipoprotein)-lowering effect in human volunteers with hyperlipidemia, a known risk factor for AD. In vitro studies have shown that LPSp treatment increases Aβ phagocytosis by microglial cells; however it is still unclear whether orally administered LPSp exhibits a preventive effect on AD progression. We show here that in senescence-accelerated prone 8 (SAMP8) mice fed a high-fat diet, oral administration of LPSp at 0.3 or 1 mg/kg body weight·day for 18 weeks significantly improved glucose metabolism and lipid profiles. The LPSp treatment also reduced pro-inflammatory cytokine expression and oxidative-burst activity in the peripheral blood. Moreover, LPSp significantly reduced brain Aβ burden and memory impairment as seen in the water maze test, although we could not confirm a significant enhancement of Aβ phagocytosis in microglia isolated from the brains after treatment. Taken together, our results show that LPSp holds promise as a preventative therapy for AD or AD-related diseases induced by impairment of metabolic functions.

Respiratory Syncytial Virus Infections Enhance Cigarette Smoke Induced COPD in Mice

PubMed Central

Foronjy, Robert F.; Dabo, Abdoulaye J.; Taggart, Clifford C.; Weldon, Sinead; Geraghty, Patrick

2014-01-01

Respiratory syncytial viral (RSV) infections are a frequent cause of chronic obstructive pulmonary disease (COPD) exacerbations, which are a major factor in disease progression and mortality. RSV is able to evade antiviral defenses to persist in the lungs of COPD patients. Though RSV infection has been identified in COPD, its contribution to cigarette smoke-induced airway inflammation and lung tissue destruction has not been established. Here we examine the long-term effects of cigarette smoke exposure, in combination with monthly RSV infections, on pulmonary inflammation, protease production and remodeling in mice. RSV exposures enhanced the influx of macrophages, neutrophils and lymphocytes to the airways of cigarette smoke exposed C57BL/6J mice. This infiltration of cells was most pronounced around the vasculature and bronchial airways. By itself, RSV caused significant airspace enlargement and fibrosis in mice and these effects were accentuated with concomitant smoke exposure. Combined stimulation with both smoke and RSV synergistically induced cytokine (IL-1α, IL-17, IFN-γ, KC, IL-13, CXCL9, RANTES, MIF and GM-CSF) and protease (MMP-2, -8, -12, -13, -16 and cathepsins E, S, W and Z) expression. In addition, RSV exposure caused marked apoptosis within the airways of infected mice, which was augmented by cigarette smoke exposure. RSV and smoke exposure also reduced protein phosphatase 2A (PP2A) and protein tyrosine phosphates (PTP1B) expression and activity. This is significant as these phosphatases counter smoke-induced inflammation and protease expression. Together, these findings show for the first time that recurrent RSV infection markedly enhances inflammation, apoptosis and tissue destruction in smoke-exposed mice. Indeed, these results indicate that preventing RSV transmission and infection has the potential to significantly impact on COPD severity and progression. PMID:24587397

Estrogen related receptor alpha in castration-resistant prostate cancer cells promotes tumor progression in bone

PubMed Central

Delliaux, Carine; Gervais, Manon; Kan, Casina; Benetollo, Claire; Pantano, Francesco; Vargas, Geoffrey; Bouazza, Lamia; Croset, Martine; Bala, Yohann; Leroy, Xavier; Rosol, Thomas J; Rieusset, Jennifer; Bellahcène, Akeila; Castronovo, Vincent; Aubin, Jane E; Clézardin, Philippe; Duterque-Coquillaud, Martine; Bonnelye, Edith

2016-01-01

Bone metastases are one of the main complications of prostate cancer and they are incurable. We investigated whether and how estrogen receptor-related receptor alpha (ERRα) is involved in bone tumor progression associated with advanced prostate cancer. By meta-analysis, we first found that ERRα expression is correlated with castration-resistant prostate cancer (CRPC), the hallmark of progressive disease. We then analyzed tumor cell progression and the associated signaling pathways in gain-of-function/loss-of-function CRPC models in vivo and in vitro. Increased levels of ERRα in tumor cells led to rapid tumor progression, with both bone destruction and formation, and direct impacts on osteoclasts and osteoblasts. VEGF-A, WNT5A and TGFβ1 were upregulated by ERRα in tumor cells and all of these factors also significantly and positively correlated with ERRα expression in CRPC patient specimens. Finally, high levels of ERRα in tumor cells stimulated the pro-metastatic factor periostin expression in the stroma, suggesting that ERRα regulates the tumor stromal cell microenvironment to enhance tumor progression. Taken together, our data demonstrate that ERRα is a regulator of CRPC cell progression in bone. Therefore, inhibiting ERRα may constitute a new therapeutic strategy for prostate cancer skeletal-related events. PMID:27776343

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions

PubMed Central

Barnes, Jessica J.; Nobre, Anna Christina; Woolrich, Mark W.; Baker, Kate

2016-01-01

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. SIGNIFICANCE STATEMENT Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called “phase amplitude coupling.” PMID:27559180

Biomaterials for Craniofacial Bone Engineering

PubMed Central

Tevlin, R.; McArdle, A.; Atashroo, D.; Walmsley, G.G.; Senarath-Yapa, K.; Zielins, E.R.; Paik, K.J.; Longaker, M.T.; Wan, D.C.

2014-01-01

Conditions such as congenital anomalies, cancers, and trauma can all result in devastating deficits of bone in the craniofacial skeleton. This can lead to significant alteration in function and appearance that may have significant implications for patients. In addition, large bone defects in this area can pose serious clinical dilemmas, which prove difficult to remedy, even with current gold standard surgical treatments. The craniofacial skeleton is complex and serves important functional demands. The necessity to develop new approaches for craniofacial reconstruction arises from the fact that traditional therapeutic modalities, such as autologous bone grafting, present myriad limitations and carry with them the potential for significant complications. While the optimal bone construct for tissue regeneration remains to be elucidated, much progress has been made in the past decade. Advances in tissue engineering have led to innovative scaffold design, complemented by progress in the understanding of stem cell–based therapy and growth factor enhancement of the healing cascade. This review focuses on the role of biomaterials for craniofacial bone engineering, highlighting key advances in scaffold design and development. PMID:25139365

Intermediate Volume on Computed Tomography Imaging Defines a Fibrotic Compartment that Predicts Glomerular Filtration Rate Decline in Autosomal Dominant Polycystic Kidney Disease Patients

PubMed Central

Caroli, Anna; Antiga, Luca; Conti, Sara; Sonzogni, Aurelio; Fasolini, Giorgio; Ondei, Patrizia; Perico, Norberto; Remuzzi, Giuseppe; Remuzzi, Andrea

2011-01-01

Total kidney and cyst volumes have been used to quantify disease progression in autosomal dominant polycystic kidney disease (ADPKD), but a causal relationship with progression to renal failure has not been demonstrated. Advanced image processing recently allowed to quantify extracystic tissue, and to identify an additional tissue component named “intermediate,” appearing hypoenhanced on contrast-enhanced computed tomography (CT). The aim of this study is to provide a histological characterization of intermediate volume, investigate its relation with renal function, and provide preliminary evidence of its role in long-term prediction of functional loss. Three ADPKD patients underwent contrast-enhanced CT scans before nephrectomy. Histological samples of intermediate volume were drawn from the excised kidneys, and stained with hematoxylin and eosin and with saturated picrosirius solution for histological analysis. Intermediate volume showed major structural changes, characterized by tubular dilation and atrophy, microcysts, inflammatory cell infiltrate, vascular sclerosis, and extended peritubular interstitial fibrosis. A significant correlation (r = −0.69, P < 0.001) between relative intermediate volume and baseline renal function was found in 21 ADPKD patients. Long-term prediction of renal functional loss was investigated in an independent cohort of 13 ADPKD patients, followed for 3 to 8 years. Intermediate volume, but not total kidney or cyst volume, significantly correlated with glomerular filtration rate decline (r = −0.79, P < 0.005). These findings suggest that intermediate volume may represent a suitable surrogate marker of ADPKD progression and a novel therapeutic target. PMID:21683674

18F-Fluorodeoxyglucose PET/CT and dynamic contrast-enhanced MRI as imaging biomarkers in malignant pleural mesothelioma.

PubMed

Hall, David O; Hooper, Clare E; Searle, Julie; Darby, Michael; White, Paul; Harvey, John E; Braybrooke, Jeremy P; Maskell, Nick A; Masani, Vidan; Lyburn, Iain D

2018-02-01

The purpose of this study was to compare the use of fluorine-18-fluorodeoxyglucose (F-FDG) PET with computed tomography (CT) and dynamic contrast-enhanced (DCE) MRI to predict prognosis and monitor treatment in malignant pleural mesothelioma. F-FDG PET/CT and DCE-MRI studies carried out as part of the South West Area Mesothelioma Pemetrexed trial were used. F-FDG PET/CT and DCE-MRI studies were carried out before treatment, and after two cycles of chemotherapy, on patients treated with pemetrexed and cisplatin. A total of 73 patients were recruited, of whom 65 had PET/CT and DCE-MRI scans. Baseline measurements from F-FDG PET/CT (maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis) and DCE-MRI (integrated area under the first 90s of the curve and washout slope) were compared with overall survival (OS) using Kaplan-Meier and Cox regression analyses, and changes in imaging measurements were compared with disease progression. PET/CT and DCE-MRI measurements were not correlated with each other. Maximum standardized uptake value, metabolic tumour volume and total lesion glycolysis were significantly related to OS with Cox regression analysis and Kaplan-Meir analysis, and DCE-MRI washout curve shape was significantly related to OS. DCE-MRI curve shape can be combined with F-FDG PET/CT to give additional prognostic information. Changes in measurements were not related to progression-free survival. F-FDG PET/CT and DCE-MRI give prognostic information in malignant pleural mesothelioma. Neither PET/CT nor DCE-MRI is useful for monitoring disease progression.

Leptomeningeal contrast enhancement is associated with progression of cortical atrophy in MS: A retrospective, pilot, observational longitudinal study.

PubMed

Zivadinov, Robert; Ramasamy, Deepa P; Vaneckova, Manuela; Gandhi, Sirin; Chandra, Avinash; Hagemeier, Jesper; Bergsland, Niels; Polak, Paul; Benedict, Ralph Hb; Hojnacki, David; Weinstock-Guttman, Bianca

2017-09-01

Leptomeningeal contrast enhancement (LM CE) has been recently described in multiple sclerosis (MS) patients as a potential in vivo marker of cortical pathology. To investigate the association of LM CE and development of cortical atrophy in 50 MS patients (27 relapsing-remitting (RR) and 23 secondary-progressive (SP)) followed for 5 years. The presence and number of LM CE foci were assessed only at the 5-year follow-up using three-dimensional (3D) fluid-attenuated inversion recovery magnetic resonance imaging (MRI) sequence obtained 10 minutes after single dose of gadolinium injection on 3T scanner. The percentage change in whole brain, cortical and deep gray matter (GM) volumes, and lesion volume (LV) was measured between baseline and the 5-year follow-up. In total, 25 (50%) of MS patients had LM CE at the 5-year follow-up. Significantly more SPMS patients (12, 85.7%) had multiple LM CE foci, compared to those with RRMS (2, 18.2%) ( p = 0.001). MS patients with LM CE showed significantly greater percentage decrease in total GM (-3.6% vs -2%, d = 0.80, p = 0.006) and cortical (-3.4% vs -1.8%, d = 0.84, p = 0.007) volumes and greater percentage increase in ventricular cerebrospinal fluid (vCSF) volume (22.8% vs 9.9%, d = 0.90, p = 0.003) over the follow-up, compared to those without. In this retrospective, pilot, observational longitudinal study, the presence of LM CE was associated with progression of cortical atrophy over 5 years.

Oxidative Stress Induced Mechanisms in the Progression of Periodontal Diseases and Cancer: A Common Approach to Redox Homeostasis?

PubMed Central

Soory, Mena

2010-01-01

There is documented evidence of significant associations between cancer of the lung, kidney, pancreas, hematological and oral cancers and periodontal diseases of the supporting structures of the teeth. Enhanced lipid peroxidation, raised levels of TBARS and the oxidative stress marker malondealdehyde have been detected in breast cancer with reduced antioxidant capacity, also characteristic of periodontal diseases. Antioxidants could overcome this deficit and attenuate disease progression by down regulating glutathione detoxification/redox buffering system and inhibiting key transcription factors. Periodontal disease may be a critical marker of a susceptible immune system, or initiate cancer risk with a pro-oxidant inflammatory profile. PMID:24281088

Radiosensitive orbital metastasis as presentation of occult colonic adenocarcinoma.

PubMed

Ludmir, Ethan B; McCall, Shannon J; Czito, Brian G; Palta, Manisha

2014-09-19

An 82-year-old man presented with progressive right frontal headaches. The patient's history was significant for benign polyps on surveillance colonoscopy 2 years prior, without high-grade dysplasia or carcinoma. MRI revealed an enhancing lesion arising within the superomedial aspect of the right orbit. Lesion biopsy demonstrated histological appearance and immunophenotype suggestive of colonic adenocarcinoma. Staging positron emission tomography/CT showed visceral metastases and diffuse activity in the posterior rectosigmoid, consistent with metastatic colon cancer. Treatment of the orbital lesion with external beam radiotherapy to 30 Gy resulted in significant palliation of the patient's headaches. The patient expired 2 months following treatment completion due to disease progression. Orbital metastasis as the initial presentation of an occult colorectal primary lesion is exceedingly rare, and occurred in this patient despite surveillance colonoscopy. Radiotherapy remains an efficacious modality for treatment of orbital metastases. 2014 BMJ Publishing Group Ltd.

Clinical Manifestations and Overall Management Strategies for Duchenne Muscular Dystrophy.

PubMed

Tsuda, Takeshi

2018-01-01

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder that causes progressive weakness and wasting of skeletal muscular and myocardium in boys due to mutation of dystrophin. The structural integrity of each individual skeletal and cardiac myocyte is significantly compromised upon physical stress due to the absence of dystrophin. The progressive destruction of systemic musculature and myocardium causes affected patients to develop multiple organ disabilities, including loss of ambulation, physical immobility, neuromuscular scoliosis, joint contracture, restrictive lung disease, obstructive sleep apnea, and cardiomyopathy. There are some central nervous system-related medical problems, as dystrophin is also expressed in the neuronal tissues. Although principal management is to mainly delay the pathological process, an enhanced understanding of underlying pathological processes has significantly improved quality of life and longevity for DMD patients. Future research in novel molecular approach is warranted to answer unanswered questions.

Therapy response assessment after radioembolization of patients with hepatocellular carcinoma--comparison of MR imaging with gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid and gadobutrol.

PubMed

Schelhorn, Juliane; Best, Jan; Reinboldt, Marcus P; Gerken, Guido; Ruhlmann, Marcus; Lauenstein, Thomas C; Antoch, Gerald; Kinner, Sonja

2015-07-01

To compare the utility of gadolinium ethoxybenzyl diethylenetriamine penta-acetic acid (Gd-EOB-DTPA), a liver-specific magnetic resonance (MR) imaging contrast agent, versus gadobutrol for treatment response evaluation of hepatocellular carcinoma (HCC) after radioembolization. This prospective study included 50 patients with HCC undergoing radioembolization. All patients underwent contrast-enhanced computed tomography (CT) and MR imaging with gadobutrol and Gd-EOB-DTPA on 2 consecutive days before radioembolization and 30 days, 90 days, 180 days, and 270 days after radioembolization. The standard of reference indicating tumor progression was CT combined with either α-fetoprotein or γ-glutamyltransferase. Gadobutrol-enhanced MR imaging, Gd-EOB-DTPA-enhanced MR imaging without late phase imaging (Gd-EOB-DTPA-), and Gd-EOB-DTPA-enhanced MR imaging with late phase imaging (Gd-EOB-DTPA+) were evaluated by 2 radiologists in consensus using a 4-point scale: 1 = definitely no tumor progression; 2 = probably no tumor progression; 3 = probably tumor progression; 4 = definitely tumor progression. Diagnostic accuracy was assessed with receiver operating characteristic analysis. Tumor progression was detected in 14 of 82 study visits according to the reference standard. Pairwise comparison of the area under the curve showed a tendency toward a larger area under the curve for Gd-EOB-DTPA+ compared with gadobutrol (P = .056). Sensitivity and specificity were higher in Gd-EOB-DTPA+ (0.929 and 0.971) than in Gd-EOB-DTPA- (0.786 and 0.941) or gadobutrol (0.643 and 0.956). In 2 cases, tumor progression was detected by Gd-EOB-DTPA+ and by an increase in α-fetoprotein, but not by CT, gadobutrol, or Gd-EOB-DTPA-. Gd-EOB-DTPA+ MR imaging was not inferior to gadobutrol-enhanced MR imaging in therapy response evaluation after radioembolization and may allow a more accurate detection of early HCC recurrence in single cases. Copyright © 2015 SIR. Published by Elsevier Inc. All rights reserved.

Nano-Bio-Mechanics of Neuroblastoma Cells Using AFM

NASA Astrophysics Data System (ADS)

Bastatas, Lyndon; Matthews, James; Kang, Min; Park, Soyeun

2011-10-01

We have conducted an in vitro study to determine the elastic moduli of neurobalstoma cell lines using atomic force microscopy. Using a panel of cell lines established from neuroblastoma patients at different stages of disease progress and treatment, we have investigated the differences in elastic moduli during a course of cancer progression and chemotherapy. The cells were grown on the hard substrates that are chemically functionalized to enhance adhesion. We have performed the AFM indentation experiments with different applied forces from the AFM probe. For the purpose of the comparison between cell lines, the indentations were performed only on cell centers. The obtained force-distance curves were analyzed using the Hertz model in order to extract the elastic moduli. We have found that the elastic moduli of human neuroblastoma cells significantly varied during the disease progression. We postulate that the observed difference might be affected by the treatment and chemotherapy.

Microglia activation in multiple sclerosis black holes predicts outcome in progressive patients: an in vivo [(11)C](R)-PK11195-PET pilot study.

PubMed

Giannetti, Paolo; Politis, Marios; Su, Paul; Turkheimer, Federico; Malik, Omar; Keihaninejad, Shiva; Wu, Kit; Reynolds, Richard; Nicholas, Richard; Piccini, Paola

2014-05-01

The pathophysiological correlates and the contribution to persisting disability of hypointense T1-weighted MRI lesions, black holes (BH), in multiple sclerosis (MS) are still unclear. In order to study the in vivo functional correlates of this MRI finding, we used 11C-PK11195 PET (PK-PET) to investigate changes in microglial activity. Ten relapsing and 9 progressive MS subjects had a PK-PET scan and a MRI scan alongside a full clinical assessment, including the expanded disability status scale (EDSS) for evaluation of disability. We studied the PK binding potential of the specifically bound radioligand relative to the non-displaceable radioligand in tissue (BPND) in T1 BHs. Out of a total of 1242 BHs identified, 947 were PK enhancing. The PKBPND was correlated with the EDSS (r=0.818; p<0.05) only in the progressive group. In the relapsing patients there was an inverse correlation between PKBPND and BH total lesion volume in whole brain (r=-0.781; p<0.05). When progressive patients were grouped according to the disability outcome at 2years from the PK-PET scan, the total PKBPND in BHs was found to be a significant outcome predictor of disability (p<0.01). Our findings show that relapsing and progressive patients have heterogeneous patterns of PKBPND in T1 BHs and indicate that BHs are not just "holes" representing loss of axons and myelin, but display inflammatory activity in the form of activated microglia. The significant association between PKBPND, neurological impairment and outcome in progressive subjects supports a role for activated microglia in disability progression. Copyright © 2014 Elsevier Inc. All rights reserved.

A Data Analysis Center for Electromagnetic and Hadronic Interaction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briscoe, William John; Strakovsky, Igor I.; Workman, Ronald L.

2015-05-31

The GW Data Analysis Center (DAC) has made significant progress in its program to enhance and expand the partial-wave and multipole analyses of fundamental reactions, while maintaining and expanding each associated database. These efforts provide guidance to national and international experimental and theoretical efforts, and are an important link between theory and experiment. Our principal goals are focused on baryon and meson physics programs and related topics.

YAC128 Huntington's disease transgenic mice show enhanced short-term hippocampal synaptic plasticity early in the course of the disease.

PubMed

Ghilan, Mohamed; Bostrom, Crystal A; Hryciw, Brett N; Simpson, Jessica M; Christie, Brian R; Gil-Mohapel, Joana

2014-09-18

Huntington's disease (HD) is a progressive and fatal neurodegenerative disorder caused by a polyglutamine expansion in the gene encoding the protein huntingtin. The disease progresses over decades, but often patients develop cognitive impairments that precede the onset of the classical motor symptoms. Similar to the disease progression in humans, the yeast artificial chromosome (YAC) 128 HD mouse model also exhibits cognitive dysfunction that precedes the onset of the neuropathological and motor impairments characteristic of HD. Thus, the purpose of this study was to evaluate whether short- and long-term synaptic plasticity in the hippocampus, two related biological models of learning and memory processes, were altered in YAC128 mice in early stages of disease progression. We show that the YAC128 hippocampal dentate gyrus (DG) displays marked reductions in paired-pulse depression both at 3 and 6 months of age. In addition, significantly enhanced post-tetanic and short-term potentiation are apparent in YAC128 mice after high-frequency stimulation at this time. Early and late forms of long-term plasticity were not altered at this stage. Together these findings indicate that there may be elevated neurotransmitter release in response to synaptic stimulation in YAC128 mice during the initial phase of disease progression. These abnormalities in short-term plasticity detected at this stage in YAC128 HD transgenic mice indicate that aberrant information processing at the level of the synapses may contribute, at least in part, to the early onset of cognitive deficits that are characteristic of this devastating neurodegenerative disorder. Copyright © 2014 Elsevier B.V. All rights reserved.

Enhanced expression of SRPK2 contributes to aggressive progression and metastasis in prostate cancer.

PubMed

Zhuo, Yang Jia; Liu, Ze Zhen; Wan, Song; Cai, Zhi Duan; Xie, Jian Jiang; Cai, Zhou da; Song, Sheng da; Wan, Yue Ping; Hua, Wei; Zhong, Wei de; Wu, Chin Lee

2018-06-01

Serine/Arginine-Rich Protein-Specific Kinase-2 (SRSF protein kinase-2, SRPK2) is up-regulated in multiple human tumors. However, the expression, function and clinical significance of SRPK2 in prostate cancer (PCa) has not yet been understood. We therefore aimed to determine the association of SRPK2 with tumor progression and metastasis in PCa patients in our present study. The expression of SRPK2 was detected by some public datasets and validated using a clinical tissue microarray (TMA) by immunohistochemistry. The association of SRPK2 expression with various clinicopathological characteristics of PCa patients was subsequently statistically analyzed based on the The Cancer Genome Atlas (TCGA) dataset and clinical TMA. The effects of SRPK2 on cancer cell proliferation, migration, invasion, cell cycle progression, apoptosis and tumor growth were then respectively investigated using in vitro and in vivo experiments. First, public datasets showed that SRPK2 expression was greater in PCa tissues when compared with non-cancerous tissues. Statistical analysis demonstrated that high expression of SRPK2 was significantly correlated with a higher Gleason Score, advanced pathological stage and the presence of tumor metastasis in the TCGA Dataset (all P < 0.01). Similar correlations between SRPK2 and a higher Gleason Score or advanced pathological stage were also identified in the TMA (P < 0.05). Kaplan-Meier curve analyses showed that the biochemical recurrence (BCR)-free time of PCa patients with SRPK2 high expression was shorter than for those with SRPK2 low expression (P < 0.05). Second, cell function experiments in PCa cell lines revealed that enhanced SRPK2 expression could promote cell proliferation, migration, invasion and cell cycle progression but suppress tumor cell apoptosis in vitro. Xenograft experiments showed that SRPK2 promoted tumor growth in vivo. In conclusion, our data demonstrated that SRPK2 may play an important role in the progression and metastasis of PCa, which suggests that it might be a potential therapeutic target for PCa clinical therapy. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Exosomes confer pro-survival signals to alter the phenotype of prostate cells in their surrounding environment

PubMed Central

Hosseini-Beheshti, Elham; Choi, Wendy; Weiswald, Louis-Bastien; Kharmate, Geetanjali; Ghaffari, Mazyar; Roshan-Moniri, Mani; Hassona, Mohamed D.; Chan, Leslie; Chin, Mei Yieng; Tai, Isabella T.; Rennie, Paul S.; Fazli, Ladan; Guns, Emma S. Tomlinson

2016-01-01

Prostate cancer (PCa) is the most frequently diagnosed cancer in men. Current research on tumour-related extracellular vesicles (EVs) suggests that exosomes play a significant role in paracrine signaling pathways, thus potentially influencing cancer progression via multiple mechanisms. In fact, during the last decade numerous studies have revealed the role of EVs in the progression of various pathological conditions including cancer. Moreover, differences in the proteomic, lipidomic, and cholesterol content of exosomes derived from PCa cell lines versus benign prostate cell lines confirm that exosomes could be excellent biomarker candidates. As such, as part of an extensive proteomic analysis using LCMS we previously described a potential role of exosomes as biomarkers for PCa. Current evidence suggests that uptake of EV's into the local tumour microenvironment encouraging us to further examine the role of these vesicles in distinct mechanisms involved in the progression of PCa and castration resistant PCa. For the purpose of this study, we hypothesized that exosomes play a pivotal role in cell-cell communication in the local tumour microenvironment, conferring activation of numerous survival mechanisms during PCa progression and development of therapeutic resistance. Our in vitro results demonstrate that PCa derived exosomes significantly reduce apoptosis, increase cancer cell proliferation and induce cell migration in LNCaP and RWPE-1 cells. In conjunction with our in vitro findings, we have also demonstrated that exosomes increased tumor volume and serum PSA levels in vivo when xenograft bearing mice were administered DU145 cell derived exosomes intravenously. This research suggests that, regardless of androgen receptor phenotype, exosomes derived from PCa cells significantly enhance multiple mechanisms that contribute to PCa progression. PMID:26840259

Non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI as a predictor of outcomes for early-stage HCC.

PubMed

Toyoda, Hidenori; Kumada, Takashi; Tada, Toshifumi; Sone, Yasuhiro; Maeda, Atsuyuki; Kaneoka, Yuji

2015-01-01

In patients with hepatocellular carcinoma (HCC), gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) often identifies non-hypervascular hypointense hepatic nodules during the hepatobiliary phase, but their prognostic significance is unclear. We conducted a prospective observational study to investigate the impact of non-hypervascular hypointense hepatic nodules detected by Gd-EOB-DTPA-enhanced MRI on the outcome of patients with early-stage HCC. Post-treatment recurrence and survival rates were analyzed in 138 patients with non-recurrent, early-stage HCC [Barcelona Clinic Liver Cancer (BCLC) stage 0 or A] and Child-Pugh A liver function according to the presence of non-hypervascular hypointense nodules on pretreatment Gd-EOB-DTPA-enhanced MRI. Non-hypervascular hypointense hepatic nodules were detected in 51 (37.0%) patients with early-stage HCC on pretreatment Gd-EOB-DTPA-enhanced MRI. Recurrence rates were significantly higher in patients with non-hypervascular hypointense nodules (p < 0.0001). Based on a multivariate analysis, the presence of non-hypervascular hypointense hepatic nodules on Gd-EOB-DTPA-enhanced MRI was independently associated with an increased recurrence rate, independent of tumor progression or treatment (p = 0.0005). The survival rate was significantly lower in patients with non-hypervascular hypointense nodules on Gd-EOB-DTPA-enhanced MRI (p = 0.0108). In patients with early-stage typical HCC (BCLC 0 or A), the presence of concurrent non-hypervascular hypointense hepatic nodules in the hepatobiliary phase of pretreatment Gd-EOB-DTPA-enhanced MRI is an indicator of higher likelihood of recurrence after treatment and may be a marker for unfavorable outcome.

The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis

PubMed Central

Clarke, Cassie J.; Berg, Tracy J.; Birch, Joanna; Ennis, Darren; Mitchell, Louise; Cloix, Catherine; Campbell, Andrew; Sumpton, David; Nixon, Colin; Campbell, Kirsteen; Bridgeman, Victoria L.; Vermeulen, Peter B.; Foo, Shane; Kostaras, Eleftherios; Jones, J. Louise; Haywood, Linda; Pulleine, Ellie; Yin, Huabing; Strathdee, Douglas; Sansom, Owen; Blyth, Karen; McNeish, Iain; Zanivan, Sara; Reynolds, Andrew R.; Norman, Jim C.

2016-01-01

Summary Expression of the initiator methionine tRNA (tRNAiMet) is deregulated in cancer. Despite this fact, it is not currently known how tRNAiMet expression levels influence tumor progression. We have found that tRNAiMet expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAiMet in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAiMet contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAiMet gene (2+tRNAiMet mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAiMet mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAiMet mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAiMet significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAiMet-overexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAiMet-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAiMet mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAiMet levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis. PMID:26948875

The Initiator Methionine tRNA Drives Secretion of Type II Collagen from Stromal Fibroblasts to Promote Tumor Growth and Angiogenesis.

PubMed

Clarke, Cassie J; Berg, Tracy J; Birch, Joanna; Ennis, Darren; Mitchell, Louise; Cloix, Catherine; Campbell, Andrew; Sumpton, David; Nixon, Colin; Campbell, Kirsteen; Bridgeman, Victoria L; Vermeulen, Peter B; Foo, Shane; Kostaras, Eleftherios; Jones, J Louise; Haywood, Linda; Pulleine, Ellie; Yin, Huabing; Strathdee, Douglas; Sansom, Owen; Blyth, Karen; McNeish, Iain; Zanivan, Sara; Reynolds, Andrew R; Norman, Jim C

2016-03-21

Expression of the initiator methionine tRNA (tRNAi(Met)) is deregulated in cancer. Despite this fact, it is not currently known how tRNAi(Met) expression levels influence tumor progression. We have found that tRNAi(Met) expression is increased in carcinoma-associated fibroblasts, implicating deregulated expression of tRNAi(Met) in the tumor stroma as a possible contributor to tumor progression. To investigate how elevated stromal tRNAi(Met) contributes to tumor progression, we generated a mouse expressing additional copies of the tRNAi(Met) gene (2+tRNAi(Met) mouse). Growth and vascularization of subcutaneous tumor allografts was enhanced in 2+tRNAi(Met) mice compared with wild-type littermate controls. Extracellular matrix (ECM) deposited by fibroblasts from 2+tRNAi(Met) mice supported enhanced endothelial cell and fibroblast migration. SILAC mass spectrometry indicated that elevated expression of tRNAi(Met) significantly increased synthesis and secretion of certain types of collagen, in particular type II collagen. Suppression of type II collagen opposed the ability of tRNAi(Met)-overexpressing fibroblasts to deposit pro-migratory ECM. We used the prolyl hydroxylase inhibitor ethyl-3,4-dihydroxybenzoate (DHB) to determine whether collagen synthesis contributes to the tRNAi(Met)-driven pro-tumorigenic stroma in vivo. DHB had no effect on the growth of syngeneic allografts in wild-type mice but opposed the ability of 2+tRNAi(Met) mice to support increased angiogenesis and tumor growth. Finally, collagen II expression predicts poor prognosis in high-grade serous ovarian carcinoma. Taken together, these data indicate that increased tRNAi(Met) levels contribute to tumor progression by enhancing the ability of stromal fibroblasts to synthesize and secrete a type II collagen-rich ECM that supports endothelial cell migration and angiogenesis. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chronic stress enhances progression of periodontitis via α1-adrenergic signaling: a potential target for periodontal disease therapy.

PubMed

Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan

2014-10-17

This study assessed the roles of chronic stress (CS) in the stimulation of the sympathetic nervous system and explored the underlying mechanisms of periodontitis. Using an animal model of periodontitis and CS, the expression of tyrosine hydroxylase (TH) and the protein levels of the α1-adrenergic receptor (α1-AR) and β2-adrenergic receptor (β2-AR) were assessed. Furthermore, human periodontal ligament fibroblasts (HPDLFs) were stimulated with lipopolysaccharide (LPS) to mimic the process of inflammation. The proliferation of the HPDLFs and the expression of α1-AR and β2-AR were assessed. The inflammatory-related cytokines interleukin (IL)-1β, IL-6 and IL-8 were detected after pretreatment with the α1/β2-AR blockers phentolamine/propranolol, both in vitro and in vivo. Results show that periodontitis under CS conditions enhanced the expression of TH, α1-AR and β2-AR. Phentolamine significantly reduced the inflammatory cytokine levels. Furthermore, we observed a marked decrease in HPDLF proliferation and the increased expression of α1-ARfollowing LPS pretreatment. Pretreatment with phentolamine dramatically ameliorated LPS-inhibited cell proliferation. In addition, the blocking of α1-ARsignaling also hindered the upregulation of the inflammatory-related cytokines IL-1β, IL-6 and IL-8. These results suggest that CS can significantly enhance the pathological progression of periodontitis by an α1-adrenergic signaling-mediated inflammatory response. We have identified a potential therapeutic target for the treatment of periodontal disease, particularly in those patients suffering from concurrent CS.

Symptomatic Therapy and Rehabilitation in Primary Progressive Multiple Sclerosis

PubMed Central

Khan, Fary; Amatya, Bhasker; Turner-Stokes, Lynne

2011-01-01

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system and a major cause of chronic neurological disability in young adults. Primary progressive MS (PPMS) constitutes about 10% of cases, and is characterized by a steady decline in function with no acute attacks. The rate of deterioration from disease onset is more rapid than relapsing remitting and secondary progressive MS types. Multiple system involvement at onset and rapid early progression have a worse prognosis. PPMS can cause significant disability and impact on quality of life. Recent studies are biased in favour of relapsing remitting patients as treatment is now available for them and they are more likely to be seen at MS clinics. Since prognosis for PPMS is worse than other types of MS, the focus of rehabilitation is on managing disability and enhancing participation, and application of a “neuropalliative” approach as the disease progresses. This chapter presents the symptomatic treatment and rehabilitation for persons with MS, including PPMS. A multidisciplinary approach optimizes the intermediate and long-term medical, psychological and social outcomes in this population. Restoration and maintenance of functional independence and societal reintegration, and issues relating to quality of life are addressed in rehabilitation processes. PMID:22013521

Lobulated Enhancement Evaluation in the Follow-Up of Liver Metastases Treated by Stereotactic Body Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jarraya, Hajer, E-mail: h-jarraya@o-lambret.fr; Borde, Paul; Mirabel, Xavier

Objective: The Response Evaluation Criteria in Solid Tumors (RECIST) can have limitations when used to evaluate local treatments for cancer, especially for liver malignancies treated by stereotactic body radiation therapy (SBRT). The aim of this study was to validate the relationship between the occurrence of lobulated enhancement (LE) and local relapse and to evaluate the utility of this relationship for predicting local progression. Patients and Methods: Imaging data of 59 lesions in 46 patients, including 281 computed tomographic (CT) scans, were retrospectively and blindly reviewed by 3 radiologists. One radiologist measured the lesion size, for each CT and overall, tomore » classify responses using RECIST threshold criteria. The second studied LE occurrence. A third radiologist was later included and studied LE occurrence to evaluate the interobserver consistency for LE evaluation. Results: The mean duration of follow-up was 13.6 months. LE was observed in 16 of 18 progressive lesions, occurring before size-based progression in 50% of cases, and the median delay of LE detection was 3.2 months. The sensitivity of LE to predict progression was 89%, and its specificity was 100%. The positive predictive value was 100%, the negative predictive value was 95.3%, and the overall accuracy was 97%. The probability of local progression-free survival at 12 months was significantly higher for lesions without LE compared with all lesions: 0.80 (CI 95%: 0.65-0.89) versus 0.69 (CI 95%: 0.54-0.80), respectively. The overall concordance rate between the 2 readers of LE was 97.9%. Conclusion: Response assessment of liver metastases treated by SBRT can be improved by including LE. This study demonstrates the diagnostic and predictive utility of LE for assessing local progression at a size still eligible for local salvage treatment.« less

Salmonella enterica Suppresses Pectobacterium carotovorum subsp. carotovorum Population and Soft Rot Progression by Acidifying the Microaerophilic Environment

PubMed Central

Kwan, Grace; Charkowski, Amy O.; Barak, Jeri D.

2013-01-01

ABSTRACT Although enteric human pathogens are usually studied in the context of their animal hosts, a significant portion of their life cycle occurs on plants. Plant disease alters the phyllosphere, leading to enhanced growth of human pathogens; however, the impact of human pathogens on phytopathogen biology and plant health is largely unknown. To characterize the interaction between human pathogens and phytobacterial pathogens in the phyllosphere, we examined the interactions between Pectobacterium carotovorum subsp. carotovorum and Salmonella enterica or Escherichia coli O157:H7 with regard to bacterial populations, soft rot progression, and changes in local pH. The presence of P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7 on leaves. However, in a microaerophilic environment, S. enterica reduced P. carotovorum subsp. carotovorum populations and soft rot progression by moderating local environmental pH. Reduced soft rot was not due to S. enterica proteolytic activity. Limitations on P. carotovorum subsp. carotovorum growth, disease progression, and pH elevation were not observed on leaves coinoculated with E. coli O157:H7 or when leaves were coinoculated with S. enterica in an aerobic environment. S. enterica also severely undermined the relationship between the phytobacterial population and disease progression of a P. carotovorum subsp. carotovorum budB mutant defective in the 2,3-butanediol pathway for acid neutralization. Our results show that S. enterica and E. coli O157:H7 interact differently with the enteric phytobacterial pathogen P. carotovorum subsp. carotovorum. S. enterica inhibition of soft rot progression may conceal a rapidly growing human pathogen population. Whereas soft rotted produce can alert consumers to the possibility of food-borne pathogens, healthy-looking produce may entice consumption of contaminated vegetables. PMID:23404399

Absence of IDH1-R132H mutation predicts rapid progression of nonenhancing diffuse glioma in older adults.

PubMed

Olar, Adriana; Raghunathan, Aditya; Albarracin, Constance T; Aldape, Kenneth D; Cahill, Daniel P; Powell, Suzanne Z; Goodman, J Clay; Fuller, Gregory N

2012-06-01

Advanced age and contrast enhancement portend a poor prognosis in diffuse glioma (DG). Diffuse glioma may present as nonenhancing tumors that rapidly progress in weeks to months to a pattern of ring enhancement, characteristic of glioblastoma (GBM). Mutations involving isocitrate dehydrogenase 1 (IDH1) have recently emerged as important diagnostic and prognostic markers in DG. R132H is the most common mutation, expressed in more than 80% of DG and secondary GBM but in less than 10% of primary GBM. Adults older than 50 years with nonenhancing, rapidly progressing DG were identified. A comparison group comprised randomly selected, age-matched patients with nonenhancing, nonprogressing DG. Isocitrate dehydrogenase 1 status was evaluated using anti-IDH1-R132H antibodies (Dianova, Hamburg, Germany). The results were correlated with the clinical outcomes. We identified 4 patients who presented with nonenhancing DG that rapidly progressed to ring-enhancing lesions that were subsequently diagnosed on surgical resection as GBM. This group showed absent IDH1-R132H expression, which is characteristic of primary GBM. The comparison group of 5 patients presented with nonenhancing, nonprogressing DG, and all 5 tumors showed IDH1-R132H expression. In conclusion, negative IDH1-R132H mutation status in nonenhancing DG of older adults is a poor prognostic factor associated with rapid progression to ring-enhancing GBM. The shorter interval of progression and negative IDH1-R132H mutation status suggest a similar molecular pathway as seen in primary GBM. Copyright © 2012 Elsevier Inc. All rights reserved.

Progress in the use of microemulsions for transdermal and dermal drug delivery.

PubMed

Ita, Kevin

2017-06-01

Transdermal drug delivery continues to attract considerable interest in the scientific community. However, due to the hindrance provided by the stratum corneum, it is not possible to deliver most medications in therapeutically significant amounts. One of the ways of increasing the penetration of drugs across the skin is through the use of microemulsions (MEs). This review focuses on the role of MEs in enhancing topical and transdermal drug delivery.

Next-Generation Molecular Histology Using Highly Multiplexed Ion Beam Imaging (MIBI) of Breast Cancer Tissue Specimens for Enhanced Clinical Guidance

DTIC Science & Technology

2015-07-01

describe: 1) major activities ; 2) specific objectives; 3) significant results or key outcomes, including major findings, developments, or conclusions...project progresses to completion, the emphasis in reporting in this section should shift from reporting activities to reporting accomplishments. B...high-resolution axial (depth) imaging as well. Of course, both techniques are under active development, and their properties may change sub

Strain Breeding Enhanced Heterologous Cellobiohydrolase Secretion by Saccharomyces cerevisiae in a Protein Specific Manner.

PubMed

Kroukamp, Heinrich; den Haan, Riaan; la Grange, Daniël C; Sibanda, Ntsako; Foulquié-Moreno, Maria R; Thevelein, Johan M; van Zyl, Willem H

2017-10-01

The yeast Saccharomyces cerevisiae has a long association with alcoholic fermentation industries and has received renewed interest as a biocatalyst for second-generation bioethanol production. Rational engineering strategies are used to create yeast strains for consolidated bioprocessing of lignocellulosic biomass. Although significant progress is made in this regard with the expression of different cellulolytic activities in yeast, cellobiohydrolase (CBH) titers remain well below ideal levels. Through classical breeding, S. cerevisiae strains with up to twofold increased CBH secretion titers is obtained in strains expressing a single gene copy. An increase of up to 3.5-fold in secreted cellobiohydrolase activity is subsequently shown for strains expressing the heterologous gene on a high copy episomal vector. To our knowledge, this is the first report of classical breeding being used to enhance heterologous protein secretion and also the most significant enhancement of CBH secretion in yeast yet reported. This enhanced secretion phenotype is specific for cellobiohydrolase I secretion, indicating that reporter protein properties might be a major determining factor for efficient protein secretion in yeast. By exploring the latent potential of different S. cerevisiae strains, the authors show that the allele pool of various strains is a valuable engineering resource to enhance secretion in yeast. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Midwest Nuclear Science and Engineering Consortium

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dr. Wynn Volkert; Dr. Arvind Kumar; Dr. Bryan Becker

2010-12-08

The objective of the Midwest Nuclear Science and Engineering Consortium (MNSEC) is to enhance the scope, quality and integration of educational and research capabilities of nuclear sciences and engineering (NS/E) programs at partner schools in support of the U.S. nuclear industry (including DOE laboratories). With INIE support, MNSEC had a productive seven years and made impressive progress in achieving these goals. Since the past three years have been no-cost-extension periods, limited -- but notable -- progress has been made in FY10. Existing programs continue to be strengthened and broadened at Consortium partner institutions. The enthusiasm generated by the academic, state,more » federal, and industrial communities for the MNSEC activities is reflected in the significant leveraging that has occurred for our programs.« less

Quantifying the remineralization of artificial caries lesions using PS-OCT

NASA Astrophysics Data System (ADS)

Jones, Robert S.; Fried, Daniel

2006-02-01

New optical imaging methods are needed to determine whether caries lesions (tooth decay) are active and progressing or have become remineralized and arrested and are no longer progressing. The objective of this study was to use Polarization Sensitive Optical Coherence Tomography (PS-OCT) to image the fluoride enhanced remineralization of artificial enamel lesions. Artificial lesions were created by an acetate buffer on smooth enamel surfaces and were exposed for 20 days to a 2 ppm fluoride containing remineralization solution. PS-OCT images revealed the presence of a low scattering surface zone after the artificial lesions were remineralized. These samples displayed intact nondepolarizing surface zones when analyzed with Polarized Light Microscopy (PLM). No statistical difference in lesion depth before and after remineralization was found with both PS-OCT and PLM. The remineralized lesions showed a significant decrease in the overall integrated reflectivity compared with the demineralized lesions. Digital Microradiography confirmed the increase in mineral volume of the remineralized surface zone. This study determined that PS-OCT can image the restoration of the surface zone enamel after fluoride-enhanced remineralization of artificial in vitro dental caries.

Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells.

PubMed

Huang, S C; Lee, T C

1998-05-01

Arsenical compounds, known to be human carcinogens, were shown to disturb cell cycle progression and induce cytogenetic alterations in a variety of cell systems. We report here that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35% of the total cell population was arrested at the mitotic stage after treatment with 5 microM sodium arsenite in HeLa S3 cells and after 10 microM in KB cells. Under a microscope, we observed abnormal mitotic figures in arsenite-arrested mitotic cells, including deranged chromosome congression, elongated polar distance of mitotic spindle, and enhanced microtubule immunofluorescence. The spindle microtubules of arsenite-arrested mitotic cells were more resistant to nocodazole-induced dissolution than those of control mitotic cells. According to turbidity assay, arsenite at concentrations below 100 microM significantly enhanced polymerization of tubulins. Since spindle dynamics play a crucial role in mitotic progression, our results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.

An Exploration of Students' Science Learning Interest Related to Their Cognitive Anxiety, Cognitive Load, Self-Confidence and Learning Progress Using Inquiry-Based Learning With an iPad

NASA Astrophysics Data System (ADS)

Hong, Jon-Chao; Hwang, Ming-Yueh; Tai, Kai-Hsin; Tsai, Chi-Ruei

2017-12-01

Based on the cognitive-affective theory, the present study designed a science inquiry learning model, predict-observe-explain (POE), and implemented it in an app called "WhyWhy" to examine the effectiveness of students' science inquiry learning practice. To understand how POE can affect the cognitive-affective learning process, as well as the learning progress, a pretest and a posttest were given to 152 grade 5 elementary school students. The students practiced WhyWhy during six sessions over 6 weeks, and data related to interest in learning science (ILS), cognitive anxiety (CA), and extraneous cognitive load (ECL) were collected and analyzed through confirmatory factor analysis with structure equation modeling. The results showed that students with high ILS have low CA and ECL. In addition, the results also indicated that students with a high level of self-confidence enhancement showed significant improvement in the posttest. The implications of this study suggest that by using technology-enhanced science learning, the POE model is a practical approach to motivate students to learn.

Enhancing Conceptual Change in Preschool Children's Representations of Light: A Sociocognitive Approach

NASA Astrophysics Data System (ADS)

Ravanis, Konstantinos; Christidou, Vasilia; Hatzinikita, Vassilia

2013-12-01

The aim of this study is to investigate the effect of a sociocognitive teaching strategy on young children's understanding of light. It explores their understanding of the concept of light as an entity that is transmitted independently of the light source and the final receiver. The study was conducted in three phases: pretest, teaching intervention, and post-tests. The sample consisted of 170 preschool children who were assigned to two groups. The children in the first group participated in activities which adopted a sociocognitive approach. In the context of this approach, a familiar metaphor was introduced in order to facilitate children to construct a "precursor model" about light. The children in the second group participated in activities with the same teaching objectives, but adopting an empiricist perspective. Statistical analysis using the Mann-Whitney U test indicated that the cognitive progress of the sociocognitive group was more significant than the progress of the empiricist group. This provides evidence for the effect of the sociocognitive strategy on enhancing children in constructing a "precursor model" for the concept of light.

Cytokine Profile in Patients with Progressive Multiple Sclerosis and Its Association with Disease Progression and Disability.

PubMed

Kallaur, Ana Paula; Oliveira, Sayonara Rangel; Simão, Andréa Name Colado; Alfieri, Daniela Frizon; Flauzino, Tamires; Lopes, Josiane; de Carvalho Jennings Pereira, Wildea Lice; de Meleck Proença, Caio; Borelli, Sueli Donizete; Kaimen-Maciel, Damacio Ramón; Maes, Michael; Reiche, Edna Maria Vissoci

2017-05-01

Inflammation is the driving force for brain injury in patients with multiple sclerosis (MS). The objective of the present study is to delineate the serum cytokine profile in patients with progressive MS in a Southern Brazilian population compared with healthy controls and patients with relapsing-remitting MS (RRMS) and its associations with disease progression and disability. We included 32 patients with progressive MS, 126 with RRMS, and 40 healthy controls. The patients were evaluated using the Expanded Disability Status Scale (EDSS) and magnetic resonance imaging (MRI) with gadolinium. Serum interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, IL-10, IL-4, and IL-17 levels were assessed using an enzyme-linked immunosorbent assay. IL-1β, IL-6, TNF-α, IFN-γ, IL-17, IL-4, and IL-10 levels were higher in progressive MS than in controls. Increased IL-1β and IFN-γ and decreased IL-12 and IL-4 levels were found in progressive MS compared with RRMS. Patients with progressive MS with disease progression presented higher TNF-α, IFN-γ, and IL-10 levels than those without disease progression. Patients with progressive MS with disease progression showed a higher frequency of positive gadolinium-enhanced lesions in MRI; higher TNF-α, IFN-γ, and IL-17 levels; and decreased IL-12 levels compared with RRMS patients with progression. There was a significant inverse correlation between IL-10 levels and EDSS score in patients with progressive MS. The results underscore the complex cytokine network imbalance exhibited by progressive MS patients and show the important involvement of TNF-α, IFN-γ, and IL-17 in the pathophysiology and progression of the disease. Moreover, serum IL-10 levels were inversely associated with disability in patients with progressive MS.

Progress and challenges in improving the nutritional quality of rice (Oryza sativa L.).

PubMed

Birla, Deep Shikha; Malik, Kapil; Sainger, Manish; Chaudhary, Darshna; Jaiwal, Ranjana; Jaiwal, Pawan K

2017-07-24

Rice is a staple food for more than 3 billion people in more than 100 countries of the world but ironically it is deficient in many bioavailable vitamins, minerals, essential amino- and fatty-acids and phytochemicals that prevent chronic diseases like type 2 diabetes, heart disease, cancers, and obesity. To enhance the nutritional and other quality aspects of rice, a better understanding of the regulation of the processes involved in the synthesis, uptake, transport, and metabolism of macro-(starch, seed storage protein and lipid) and micronutrients (vitamins, minerals and phytochemicals) is required. With the publication of high quality genomic sequence of rice, significant progress has been made in identification, isolation, and characterization of novel genes and their regulation for the nutritional and quality enhancement of rice. During the last decade, numerous efforts have been made to refine the nutritional and other quality traits either by using the traditional breeding with high through put technologies such as marker assisted selection and breeding, or by adopting the transgenic approach. A significant improvement in vitamins (A, folate, and E), mineral (iron), essential amino acid (lysine), and flavonoids levels has been achieved in the edible part of rice, i.e., endosperm (biofortification) to meet the daily dietary allowance. However, studies on bioavailability and allergenicity on biofortified rice are still required. Despite the numerous efforts, the commercialization of biofortified rice has not yet been achieved. The present review summarizes the progress and challenges of genetic engineering and/or metabolic engineering technologies to improve rice grain quality, and presents the future prospects in developing nutrient dense rice to save the everincreasing population, that depends solely on rice as the staple food, from widespread nutritional deficiencies.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy.

PubMed

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-12-01

The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02-6.80, P=0.04), SLPECC inferior RNFLT (per -1 μm, HR=1.38, 95% CI: 1.02-2.2, P=0.02), and TDOCT inferior RNFLT (per -1 μm, HR=1.11, 95% CI: 1.04-1.2, P=0.001) had significant HRs for SAP progression. Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes.

Evaluation of baseline structural factors for predicting glaucomatous visual-field progression using optical coherence tomography, scanning laser polarimetry and confocal scanning laser ophthalmoscopy

PubMed Central

Sehi, M; Bhardwaj, N; Chung, Y S; Greenfield, D S

2012-01-01

Purpose The objective of this study is to assess whether baseline optic nerve head (ONH) topography and retinal nerve fiber layer thickness (RNFLT) are predictive of glaucomatous visual-field progression in glaucoma suspect (GS) and glaucomatous eyes, and to calculate the level of risk associated with each of these parameters. Methods Participants with ≥28 months of follow-up were recruited from the longitudinal Advanced Imaging for Glaucoma Study. All eyes underwent standard automated perimetry (SAP), confocal scanning laser ophthalmoscopy (CSLO), time-domain optical coherence tomography (TDOCT), and scanning laser polarimetry using enhanced corneal compensation (SLPECC) every 6 months. Visual-field progression was assessed using pointwise linear-regression analysis of SAP sensitivity values (progressor) and defined as significant sensitivity loss of >1 dB/year at ≥2 adjacent test locations in the same hemifield at P<0.01. Cox proportional hazard ratios (HR) were calculated to determine the predictive ability of baseline ONH and RNFL parameters for SAP progression using univariate and multivariate models. Results Seventy-three eyes of 73 patients (43 GS and 30 glaucoma, mean age 63.2±9.5 years) were enrolled (mean follow-up 51.5±11.3 months). Four of 43 GS (9.3%) and 6 of 30 (20%) glaucomatous eyes demonstrated progression. Mean time to progression was 50.8±11.4 months. Using multivariate models, abnormal CSLO temporal-inferior Moorfields classification (HR=3.76, 95% confidence interval (CI): 1.02–6.80, P=0.04), SLPECC inferior RNFLT (per −1 μm, HR=1.38, 95% CI: 1.02–2.2, P=0.02), and TDOCT inferior RNFLT (per −1 μm, HR=1.11, 95% CI: 1.04–1.2, P=0.001) had significant HRs for SAP progression. Conclusion Abnormal baseline ONH topography and reduced inferior RNFL are predictive of SAP progression in GS and glaucomatous eyes. PMID:23060026

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies.

PubMed

Sosenko, Jay M; Yu, Liping; Skyler, Jay S; Krischer, Jeffrey P; Gottlieb, Peter A; Boulware, David; Miao, Dongmei; Palmer, Jerry P; Steck, Andrea K

2017-03-01

Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies. TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL + ) were compared with those ECL negative (ECL - ) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D. The progression to multiple autoantibodies was significantly higher for those GADA/ECL + (n = 107) than those GADA/ECL - (n = 78) (P = 0.001) and for those mIAA/ECL + (n = 24) than those mIAA/ECL - (n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58-7.39; P < 0.01) for GADA and 8.15 (3.02-22.00; P < 0.001) for mIAA. GADA/ECL + and mIAA/ECL + participants had significantly higher PS6M values than their ECL - counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ECL + , 14% progressed to T1D; of those mIAA/ECL + , 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL - progressed to T1D (median follow-up: 5 years). ECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL + are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL - are at very low risk.

The Impact of Retardance Pattern Variability on Nerve Fiber Layer Measurements over Time Using GDx with Variable and Enhanced Corneal Compensation

PubMed Central

Grewal, Dilraj S.; Sehi, Mitra; Cook, Richard J.

2011-01-01

Purpose. To examine the impact of retardance pattern variability on retinal nerve fiber layer (RNFL) measurements over time using scanning laser polarimetry with variable (GDxVCC) and enhanced corneal compensation (GDxECC; both by Carl Zeiss Meditec, Inc., Dublin, CA). Methods. Glaucoma suspect and glaucomatous eyes with 4 years of follow-up participating in the Advanced Imaging in Glaucoma Study were prospectively enrolled. All eyes underwent standard automated perimetry (SAP), GDxVCC, and GDxECC imaging every 6 months. SAP progression was determined with point-wise linear regression analysis of SAP sensitivity values. Typical scan score (TSS) values were extracted as a measure of retardance image quality; an atypical retardation pattern (ARP) was defined as TSS < 80. TSS fluctuation over time was measured using three parameters: change in TSS from baseline, absolute difference (maximum minus minimum TSS value), and TSS variance. Linear mixed-effects models that accommodated the association between the two eyes were constructed to evaluate the relationship between change in TSS and RNFL thickness over time. Results. Eighty-six eyes (51 suspected glaucoma, 35 glaucomatous) of 45 patients were enrolled. Twenty (23.3%) eyes demonstrated SAP progression. There was significantly greater fluctuation in TSS over time with GDxVCC compared with GDxECC as measured by absolute difference (18.40 ± 15.35 units vs. 2.50 ± 4.69 units; P < 0.001), TSS variance (59.63 ± 87.27 units vs. 3.82 ± 9.63 units, P < 0.001), and change in TSS from baseline (−0.83 ± 11.2 vs. 0.25 ± 2.9, P = 0.01). The change in TSS over time significantly (P = 0.006) influenced the TSNIT average RNFL thickness when measured by GDxVCC but not by GDxECC. Conclusions. Longitudinal images obtained with GDxECC have significantly less variability in TSS and retardance patterns and have reduced bias produced by ARP on RNFL progression assessment. PMID:21296821

Au@Pt nanoparticles as catalase mimics to attenuate tumor hypoxia and enhance immune cell-mediated cytotoxicity

NASA Astrophysics Data System (ADS)

Liang, Hong; Wu, Ying; Ou, Xiang-Yu; Li, Jing-Ying; Li, Juan

2017-11-01

Hypoxic tumor microenvironment (TME) is closely linked to tumor progression, heterogeneity and immune suppression. Therefore, the development of effective methods to overcome hypoxia and substantially enhance the immunotherapy efficacy remains a desirable goal. Herein, we engineered a biocompatible Au core/Pt shell nanoparticles (Au@Pt NPs) to reoxygenate the TME by reacting with endogenous H2O2. Treatment with Au@Pt NPs appeared to improve oxygen in intracellular environments and decrease hypoxia-inducible factor-1α expression. Furthermore, the integration of high catalytic efficiency of Au@Pt NPs with cytokine-induced killer (CIK) cell immunotherapy, could lead to significantly improve the effect of CIK cell-mediated cytotoxicity. These results suggest great potential of Au@Pt NPs for regulation of the hypoxic TME and enhance immune cell mediated anti-tumor immunity.

Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis.

PubMed

Das, Biplab; Goyal, Manoj Kumar; Modi, Manish; Mehta, Sahil; Chakravarthi, Sudheer; Lal, Vivek; Vyas, Sameer

2016-01-01

Subacute sclerosing panencephalitis (SSPE) is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage. Heterogeneity of imaging findings in SSPE is not very uncommon. But pial and gyral enhancements are very rarely noticed. Significant asymmetric onset as well as pial-gyral enhancements is not reported. Herein we present a case of 16 years adolescent of SSPE having remarkable asymmetric pial-gyral enhancements, which were misinterpreted as tubercular infection. Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case.

Final Project Report: Data Locality Enhancement of Dynamic Simulations for Exascale Computing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Xipeng

The goal of this project is to develop a set of techniques and software tools to enhance the matching between memory accesses in dynamic simulations and the prominent features of modern and future manycore systems, alleviating the memory performance issues for exascale computing. In the first three years, the PI and his group have achieves some significant progress towards the goal, producing a set of novel techniques for improving the memory performance and data locality in manycore systems, yielding 18 conference and workshop papers and 4 journal papers and graduating 6 Ph.Ds. This report summarizes the research results of thismore » project through that period.« less

Nanomaterial-Based Plasmon-Enhanced Infrared Spectroscopy.

PubMed

Yang, Xiaoxia; Sun, Zhipei; Low, Tony; Hu, Hai; Guo, Xiangdong; García de Abajo, F Javier; Avouris, Phaedon; Dai, Qing

2018-05-01

Surface-enhanced infrared absorption (SEIRA) has attracted increasing attention due to the potential of infrared spectroscopy in applications such as molecular trace sensing of solids, polymers, and proteins, specifically fueled by recent substantial developments in infrared plasmonic materials and engineered nanostructures. Here, the significant progress achieved in the past decades is reviewed, along with the current state of the art of SEIRA. In particular, the plasmonic properties of a variety of nanomaterials are discussed (e.g., metals, semiconductors, and graphene) along with their use in the design of efficient SEIRA configurations. To conclude, perspectives on potential applications, including single-molecule detection and in vivo bioassays, are presented. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The specificity of memory enhancement during interaction with a virtual environment.

PubMed

Brooks, B M; Attree, E A; Rose, F D; Clifford, B R; Leadbetter, A G

1999-01-01

Two experiments investigated differences between active and passive participation in a computer-generated virtual environment in terms of spatial memory, object memory, and object location memory. It was found that active participants, who controlled their movements in the virtual environment using a joystick, recalled the spatial layout of the virtual environment better than passive participants, who merely watched the active participants' progress. Conversely, there were no significant differences between the active and passive participants' recall or recognition of the virtual objects, nor in their recall of the correct locations of objects in the virtual environment. These findings are discussed in terms of subject-performed task research and the specificity of memory enhancement in virtual environments.

Optofluidic platforms based on surface-enhanced Raman scattering.

PubMed

Lim, Chaesung; Hong, Jongin; Chung, Bong Geun; deMello, Andrew J; Choo, Jaebum

2010-05-01

We report recent progress in the development of surface-enhanced Raman scattering (SERS)-based optofluidic platforms for the fast and sensitive detection of chemical and biological analytes. In the current context, a SERS-based optofluidic platform is defined as an integrated analytical device composed of a microfluidic element and a sensitive Raman spectrometer. Optofluidic devices for SERS detection normally involve nanocolloid-based microfluidic systems or metal nanostructure-embedded microfluidic systems. In the current review, recent advances in both approaches are surveyed and assessed. Additionally, integrated real-time sensing systems that combine portable Raman spectrometers with microfluidic devices are also reviewed. Such real-time sensing systems have significant utility in environmental monitoring, forensic science and homeland defense applications.

Using filtered forecasting techniques to determine personalized monitoring schedules for patients with open-angle glaucoma.

PubMed

Schell, Greggory J; Lavieri, Mariel S; Helm, Jonathan E; Liu, Xiang; Musch, David C; Van Oyen, Mark P; Stein, Joshua D

2014-08-01

To determine whether dynamic and personalized schedules of visual field (VF) testing and intraocular pressure (IOP) measurements result in an improvement in disease progression detection compared with fixed interval schedules for performing these tests when evaluating patients with open-angle glaucoma (OAG). Secondary analyses using longitudinal data from 2 randomized controlled trials. A total of 571 participants from the Advanced Glaucoma Intervention Study (AGIS) and the Collaborative Initial Glaucoma Treatment Study (CIGTS). Perimetric and tonometric data were obtained for AGIS and CIGTS trial participants and used to parameterize and validate a Kalman filter model. The Kalman filter updates knowledge about each participant's disease dynamics as additional VF tests and IOP measurements are obtained. After incorporating the most recent VF and IOP measurements, the model forecasts each participant's disease dynamics into the future and characterizes the forecasting error. To determine personalized schedules for future VF tests and IOP measurements, we developed an algorithm by combining the Kalman filter for state estimation with the predictive power of logistic regression to identify OAG progression. The algorithm was compared with 1-, 1.5-, and 2-year fixed interval schedules of obtaining VF and IOP measurements. Length of diagnostic delay in detecting OAG progression, efficiency of detecting progression, and number of VF and IOP measurements needed to assess for progression. Participants were followed in the AGIS and CIGTS trials for a mean (standard deviation) of 6.5 (2.8) years. Our forecasting model achieved a 29% increased efficiency in identifying OAG progression (P<0.0001) and detected OAG progression 57% sooner (reduced diagnostic delay) (P = 0.02) than following a fixed yearly monitoring schedule, without increasing the number of VF tests and IOP measurements required. The model performed well for patients with mild and advanced disease. The model performed significantly more testing of patients who exhibited OAG progression than nonprogressing patients (1.3 vs. 1.0 tests per year; P<0.0001). Use of dynamic and personalized testing schedules can enhance the efficiency of OAG progression detection and reduce diagnostic delay compared with yearly fixed monitoring intervals. If further validation studies confirm these findings, such algorithms may be able to greatly enhance OAG management. Copyright © 2014 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Training Working Memory in Childhood Enhances Coupling between Frontoparietal Control Network and Task-Related Regions.

PubMed

Barnes, Jessica J; Nobre, Anna Christina; Woolrich, Mark W; Baker, Kate; Astle, Duncan E

2016-08-24

Working memory is a capacity upon which many everyday tasks depend and which constrains a child's educational progress. We show that a child's working memory can be significantly enhanced by intensive computer-based training, relative to a placebo control intervention, in terms of both standardized assessments of working memory and performance on a working memory task performed in a magnetoencephalography scanner. Neurophysiologically, we identified significantly increased cross-frequency phase amplitude coupling in children who completed training. Following training, the coupling between the upper alpha rhythm (at 16 Hz), recorded in superior frontal and parietal cortex, became significantly coupled with high gamma activity (at ∼90 Hz) in inferior temporal cortex. This altered neural network activity associated with cognitive skill enhancement is consistent with a framework in which slower cortical rhythms enable the dynamic regulation of higher-frequency oscillatory activity related to task-related cognitive processes. Whether we can enhance cognitive abilities through intensive training is one of the most controversial topics of cognitive psychology in recent years. This is particularly controversial in childhood, where aspects of cognition, such as working memory, are closely related to school success and are implicated in numerous developmental disorders. We provide the first neurophysiological account of how working memory training may enhance ability in childhood, using a brain recording technique called magnetoencephalography. We borrowed an analysis approach previously used with intracranial recordings in adults, or more typically in other animal models, called "phase amplitude coupling." Copyright © 2016 Barnes et al.

Preventive effects of conservative treatment with short-term teriparatide on the progression of vertebral body collapse after osteoporotic vertebral compression fracture.

PubMed

Park, J-H; Kang, K-C; Shin, D-E; Koh, Y-G; Son, J-S; Kim, B-H

2014-02-01

The progression of fractured vertebral collapse is not rare after a conservative treatment of vertebral compression fracture (VCF). Teriparatide has been shown to directly stimulate bone formation and improve bone density, but there is a lack of evidence regarding its use in fracture management. Conservative treatment with short-term teriparatide is effective for decreasing the progression of fractured vertebral body collapse. Few studies have reported on the prevention of collapsed vertebral body progression after osteoporotic VCF. Teriparatide rapidly enhances bone formation and increases bone strength. This study evaluated preventive effects of short-term teriparatide on the progression of vertebral body collapse after osteoporotic VCF. Radiographs of 68 women with single-level osteoporotic VCF at thoracolumbar junction (T11-L2) were reviewed. Among them, 32 patients were treated conservatively with teriparatide (minimum 3 months) (group I), and 36 were treated with antiresorptive (group II). We measured kyphosis and wedge angle of the fractured vertebral body, and ratios of anterior, middle, and posterior heights of the collapsed body to posterior height of a normal upper vertebra were determined. The degree of collapse progression was compared between two groups. The progression of fractured vertebral body collapse was shown in both groups, but the degree of progression was significantly lower in group I than in group II. At the last follow-up, mean increments of kyphosis and wedge angle were significantly lower in group I (4.0° ± 4.2° and 3.6° ± 3.6°) than in group II (6.8° ± 4.1° and 5.8° ± 3.5°) (p = 0.032 and p = 0.037). Decrement percentages of anterior and middle border height were significantly lower in group I (9.6 ± 10.3 and 7.4 ± 7.5 %) than in group II (18.1 ± 9.7 and 13.8 ± 12.2 %) (p = 0.001 and p = 0.025), but not in posterior height (p = 0.086). In female patients with single-level osteoporotic VCF at the thoracolumbar junction, short-term teriparatide treatment did not prevent but did decrease the progression of fractured vertebral body collapse.

Induction of monocyte chemoattractant protein-1 and interleukin-10 by TGFbeta1 in melanoma enhances tumor infiltration and immunosuppression.

PubMed

Díaz-Valdés, Nancy; Basagoiti, María; Dotor, Javier; Aranda, Fernando; Monreal, Iñaki; Riezu-Boj, José Ignacio; Borrás-Cuesta, Francisco; Sarobe, Pablo; Feijoó, Esperanza

2011-02-01

Melanoma progression is associated with the expression of different growth factors, cytokines, and chemokines. Because TGFβ1 is a pleiotropic cytokine involved not only in physiologic processes but also in cancer development, we analyzed in A375 human melanoma cells, the effect of TGFβ1 on monocyte chemoattractant protein-1 (MCP-1) and interleukin-10 (IL-10) expression, two known factors responsible for melanoma progression. TGFβ1 increased the expression of MCP-1 and IL-10 in A375 cells, an effect mediated by the cross-talk between Smad, PI3K (phosphoinositide 3-kinase)/AKT, and BRAF-MAPK (mitogen activated protein kinase) signaling pathways. Supernatants from TGFβ1-treated A375 cells enhanced MCP-1-dependent migration of monocytes, which, in turn, expressed high levels of TGF,β1, bFGF, and VEGF mRNA. Moreover, these supernatants also inhibited functional properties of dendritic cells through IL-10-dependent mechanisms. When using in vitro, the TGFβ1-blocking peptide P144, TGFβ1-dependent Smad3 phosphorylation, and expression of MCP-1 and IL-10 were inhibited. In vivo, treatment of A375 tumor-bearing athymic mice with P144 significantly reduced tumor growth, associated with a lower macrophage infiltrate and decreased intratumor MCP-1 and VEGF levels, as well as angiogenesis. Finally, in C57BL/6 mice with B16-OVA melanoma tumors, when administered with immunotherapy, P144 decreased tumor growth and intratumor IL-10 levels, linked to enhanced activation of dendritic cells and natural killer cells, as well as anti-OVA T-cell responses. These results show new effects of TGFβ1 on melanoma cells, which promote tumor progression and immunosuppression, strongly reinforcing the relevance of this cytokine as a molecular target in melanoma.

Loss of HCN1 enhances disease progression in mouse models of CNG channel-linked retinitis pigmentosa and achromatopsia.

PubMed

Schön, Christian; Asteriti, Sabrina; Koch, Susanne; Sothilingam, Vithiyanjali; Garcia Garrido, Marina; Tanimoto, Naoyuki; Herms, Jochen; Seeliger, Mathias W; Cangiano, Lorenzo; Biel, Martin; Michalakis, Stylianos

2016-03-15

Most inherited blinding diseases are characterized by compromised retinal function and progressive degeneration of photoreceptors. However, the factors that affect the life span of photoreceptors in such degenerative retinal diseases are rather poorly understood. Here, we explore the role of hyperpolarization-activated cyclic nucleotide-gated channel 1 (HCN1) in this context. HCN1 is known to adjust retinal function under mesopic conditions, and although it is expressed at high levels in rod and cone photoreceptor inner segments, no association with any retinal disorder has yet been found. We investigated the effects of an additional genetic deletion of HCN1 on the function and survival of photoreceptors in a mouse model of CNGB1-linked retinitis pigmentosa (RP). We found that the absence of HCN1 in Cngb1 knockout (KO) mice exacerbated photoreceptor degeneration. The deleterious effect was reduced by expression of HCN1 using a viral vector. Moreover, pharmacological inhibition of HCN1 also enhanced rod degeneration in Cngb1 KO mice. Patch-clamp recordings revealed that the membrane potentials of Cngb1 KO and Cngb1/Hcn1 double-KO rods were both significantly depolarized. We also found evidence for altered calcium homeostasis and increased activation of the protease calpain in Cngb1/Hcn1 double-KO mice. Finally, the deletion of HCN1 also exacerbated degeneration of cone photoreceptors in a mouse model of CNGA3-linked achromatopsia. Our results identify HCN1 as a major modifier of photoreceptor degeneration and suggest that pharmacological inhibition of HCN channels may enhance disease progression in RP and achromatopsia patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Tribulus terrestris Extract Improves Human Sperm Parameters In Vitro

PubMed Central

Khaleghi, Sara; Bakhtiari, Mitra; Asadmobini, Atefeh; Esmaeili, Farzane

2016-01-01

Objective. The object of present study was to investigate the effects of direct addition of Tribulus terrestris extract on human sperm parameters. Design. Semen specimens from 40 healthy men volunteers were divided into 4 groups: one group received no treatment (control group) while the others were incubated with 20, 40, and 50 µg/mL of T terrestris extract (experimental groups). Motility, viability, and DNA fragmentation were assessed in all groups. Results. The incubation of human semen with 40 and 50 μg/mL of T terrestris extract significantly enhanced total sperm motility, number of progressive motile spermatozoa, and curvilinear velocity over 60 to 120 minutes’ holding time (P < .05 or P < < .01). Furthermore, viability was significantly enhanced by using T terrestris extract (P < .01). Conclusions. In vitro addition of the T terrestris extract to human sperm could affect male fertility capacity. PMID:27694560

Tribulus terrestris Extract Improves Human Sperm Parameters In Vitro.

PubMed

Khaleghi, Sara; Bakhtiari, Mitra; Asadmobini, Atefeh; Esmaeili, Farzane

2016-09-30

The object of present study was to investigate the effects of direct addition of Tribulus terrestris extract on human sperm parameters. Semen specimens from 40 healthy men volunteers were divided into 4 groups: one group received no treatment (control group) while the others were incubated with 20, 40, and 50 µg/mL of T terrestris extract (experimental groups). Motility, viability, and DNA fragmentation were assessed in all groups. The incubation of human semen with 40 and 50 μg/mL of T terrestris extract significantly enhanced total sperm motility, number of progressive motile spermatozoa, and curvilinear velocity over 60 to 120 minutes' holding time (P < .05 or P < < .01). Furthermore, viability was significantly enhanced by using T terrestris extract (P < .01). In vitro addition of the T terrestris extract to human sperm could affect male fertility capacity. © The Author(s) 2016.

Recent Progress in Virtual Reality Exposure Therapy for Phobias: A Systematic Review.

PubMed

Botella, Cristina; Fernández-Álvarez, Javier; Guillén, Verónica; García-Palacios, Azucena; Baños, Rosa

2017-07-01

This review is designed to systematically examine the available evidence about virtual reality exposure therapy's (VRET) efficacy for phobias, critically describe some of the most important challenges in the field and discuss possible directions. Evidence reveals that virtual reality (VR) is an effective treatment for phobias and useful for studying specific issues, such as pharmacological compounds and behavioral manipulations, that can enhance treatment outcomes. In addition, some variables, such as sense of presence in virtual environments, have a significant influence on outcomes, but further research is needed to better understand their role in therapeutic outcomes. We conclude that VR is a useful tool to improve exposure therapy and it can be a good option to analyze the processes and mechanisms involved in exposure therapy and the ways this strategy can be enhanced. In the coming years, there will be a significant expansion of VR in routine practice in clinical contexts.

Queerin' the PGD clinic : human enhancement and the future of bodily diversity.

PubMed

Sparrow, Robert

2013-06-01

Disability activists influenced by queer theory and advocates of "human enhancement" have each disputed the idea that what is "normal" is normatively significant, which currently plays a key role in the regulation of pre-implantation genetic diagnosis (PGD). Previously, I have argued that the only way to avoid the implication that parents have strong reasons to select children of one sex (most plausibly, female) over the other is to affirm the moral significance of sexually dimorphic human biological norms. After outlining the logic that generates this conclusion, I investigate the extent to which it might also facilitate an alternative, progressive, opening up of the notion of the normal and of the criteria against which we should evaluate the relative merits of different forms of embodiment. This paper therefore investigates the implications of ideas derived from queer theory for the future of PGD and of PGD for the future of queerness.

Information Tailoring Enhancements for Large-Scale Social Data

DTIC Science & Technology

2016-06-15

Intelligent Automation Incorporated Information Tailoring Enhancements for Large-Scale... Automation Incorporated Progress Report No. 3 Information Tailoring Enhancements for Large-Scale Social Data Submitted in accordance with...1 Work Performed within This Reporting Period .................................................... 2 1.1 Enhanced Named Entity Recognition (NER

Sex differences and the role of dopamine receptors in the reward-enhancing effects of nicotine and bupropion.

PubMed

Barrett, Scott T; Geary, Trevor N; Steiner, Amy N; Bevins, Rick A

2017-01-01

Nicotine and bupropion have been demonstrated to enhance the value of other reinforcers, and this may partially account for nicotine reward and dependence. Evidence suggests that the sexes differ in their sensitivity to the primary and secondary reinforcing effects of nicotine and nicotine-associated stimuli. Whether the sexes also differ in sensitivity to the reward-enhancing effects of nicotine (and bupropion) is yet unclear. The present study evaluated potential sex differences in the enhancement effects of nicotine and bupropion using a reinforcer demand approach. Furthermore, we sought to investigate the role that D1- and D2-type dopamine receptors play in the reward-enhancing effects of nicotine and bupropion. Demand for sensory reinforcement was assessed in male and female rats responding on a progression of fixed ratio schedules. The effects of nicotine and 10 or 20 mg/kg bupropion on reinforcer demand were assessed within subjects. Subsequently, the effects of SCH-23390 and eticlopride were assessed on the enhancing effects of nicotine and bupropion on progressive ratio responding. Nicotine and bupropion enhanced demand metrics of reinforcement value in both sexes. Females were more sensitive to the enhancement effects of bupropion assessed by reinforcer demand and progressive ratio performance. D2-like dopamine receptor antagonism by eticlopride attenuated the enhancement effects of bupropion, but not of nicotine. Nicotine and bupropion both enhance reinforcement value in both sexes, though females may be more sensitive to the reward-enhancing effects of bupropion. D2- and possibly D1-type receptors appear to be involved in the reward-enhancing effects of bupropion, but not necessarily nicotine.

Responses of peripheral endocannabinoids and endocannabinoid-related compounds to hedonic eating in obesity.

PubMed

Monteleone, A M; Di Marzo, V; Monteleone, P; Dalle Grave, R; Aveta, T; Ghoch, M El; Piscitelli, F; Volpe, U; Calugi, S; Maj, M

2016-06-01

Hedonic eating occurs independently from homeostatic needs prompting the ingestion of pleasurable foods that are typically rich in fat, sugar and/or salt content. In normal weight healthy subjects, we found that before hedonic eating, plasma levels of 2-arachidonoylglycerol (2-AG) were higher than before nonhedonic eating, and although they progressively decreased after food ingestion in both eating conditions, they were significantly higher in hedonic eating. Plasma levels of anandamide (AEA), oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), instead, progressively decreased in both eating conditions without significant differences. In this study, we investigated the responses of AEA, 2-AG, OEA and PEA to hedonic eating in obese individuals. Peripheral levels of AEA, 2-AG, OEA and PEA were measured in 14 obese patients after eating favourite (hedonic eating) and non-favourite (nonhedonic eating) foods in conditions of no homeostatic needs. Plasma levels of 2-AG increased after eating the favourite food, whereas they decreased after eating the non-favourite food, with the production of the endocannabinoid being significantly enhanced in hedonic eating. Plasma levels of AEA decreased progressively in nonhedonic eating, whereas they showed a decrease after the exposure to the favourite food followed by a return to baseline values after eating it. No significant differences emerged in plasma OEA and PEA responses to favourite and non-favourite food. Present findings compared with those obtained in our previously studied normal weight healthy subjects suggest deranged responses of endocannabinoids to food-related reward in obesity.

Withdrawal of repeated morphine enhances histamine-induced scratching responses in mice.

PubMed

Abe, Kenji; Kobayashi, Kanayo; Yoshino, Saori; Taguchi, Kyoji; Nojima, Hiroshi

2015-04-01

An itch is experientially well known that the scratching response of conditions such as atopic dermatitis is enhanced under psychological stress. Morphine is typical narcotic drug that induces a scratching response upon local application as an adverse drug reaction. Although long-term treatment with morphine will cause tolerance and dependence, morphine withdrawal can cause psychologically and physiologically stressful changes in humans. In this study, we evaluated the effects of morphine withdrawal on histamine-induced scratching behavior in mice. Administration of morphine with progressively increasing doses (10-50 mg/kg, i.p.) was performed for 5 consecutive days. At 3, 24, 48, and 72 hr after spontaneous withdrawal from the final morphine dose, histamine was intradermally injected into the rostral part of the back and then the number of bouts of scratching in 60 min was recorded and summed. We found that at 24 hr after morphine withdrawal there was a significant increase in histamine-induced scratching behavior. The spinal c-Fos positive cells were also significantly increased. The relative adrenal weight increased and the relative thymus weight decreased, both significantly. Moreover, the plasma corticosterone levels changed in parallel with the number of scratching bouts. These results suggest that morphine withdrawal induces a stressed state and enhances in histamine-induced scratching behavior. Increased reaction against histamine in the cervical vertebrae will participate in this stress-induced itch enhancement.

Hypoxia Potentiates Anabolic Effects of Exogenous Hyaluronic Acid in Rat Articular Cartilage

PubMed Central

Ichimaru, Shohei; Nakagawa, Shuji; Arai, Yuji; Kishida, Tsunao; Shin-Ya, Masaharu; Honjo, Kuniaki; Tsuchida, Shinji; Inoue, Hiroaki; Fujiwara, Hiroyoshi; Shimomura, Seiji; Mazda, Osam; Kubo, Toshikazu

2016-01-01

Hyaluronic acid (HA) is used clinically to treat osteoarthritis (OA), but its pharmacological effects under hypoxic conditions remain unclear. Articular chondrocytes in patients with OA are exposed to a hypoxic environment. This study investigated whether hypoxia could potentiate the anabolic effects of exogenous HA in rat articular cartilage and whether these mechanisms involved HA receptors. HA under hypoxic conditions significantly enhanced the expression of extracellular matrix genes and proteins in explant culture, as shown by real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and dimethylmethylene blue (DMMB) assays. Staining with Safranin-O and immunohistochemical staining with antibody to type II collagen were also enhanced in pellet culture. The expression of CD44 was increased by hypoxia and significantly suppressed by transfection with siRNAs targeting hypoxia-inducible factor 1 alpha (siHIF-1α). These findings indicate that hypoxia potentiates the anabolic effects of exogenous HA by a mechanism in which HIF-1α positively regulates the expression of CD44, enhancing the binding affinity for exogenous HA. The anabolic effects of exogenous HA may increase as OA progresses. PMID:27347945

Ab initio optimization of phonon drag effect for lower-temperature thermoelectric energy conversion.

PubMed

Zhou, Jiawei; Liao, Bolin; Qiu, Bo; Huberman, Samuel; Esfarjani, Keivan; Dresselhaus, Mildred S; Chen, Gang

2015-12-01

Although the thermoelectric figure of merit zT above 300 K has seen significant improvement recently, the progress at lower temperatures has been slow, mainly limited by the relatively low Seebeck coefficient and high thermal conductivity. Here we report, for the first time to our knowledge, success in first-principles computation of the phonon drag effect--a coupling phenomenon between electrons and nonequilibrium phonons--in heavily doped region and its optimization to enhance the Seebeck coefficient while reducing the phonon thermal conductivity by nanostructuring. Our simulation quantitatively identifies the major phonons contributing to the phonon drag, which are spectrally distinct from those carrying heat, and further reveals that although the phonon drag is reduced in heavily doped samples, a significant contribution to Seebeck coefficient still exists. An ideal phonon filter is proposed to enhance zT of silicon at room temperature by a factor of 20 to ∼ 0.25, and the enhancement can reach 70 times at 100 K. This work opens up a new venue toward better thermoelectrics by harnessing nonequilibrium phonons.

Neuropilin 1 deficiency on CD4+Foxp3+ regulatory T cells impairs mouse melanoma growth

PubMed Central

Hutzler, Marina; Abel, Simone; Alter, Christina; Stockmann, Christian; Kliche, Stefanie; Albert, Juliane; Sparwasser, Tim; Sakaguchi, Shimon; Westendorf, Astrid M.; Schadendorf, Dirk; Buer, Jan; Helfrich, Iris

2012-01-01

Infiltration of Foxp3+ regulatory T (T reg) cells is considered to be a critical step during tumor development and progression. T reg cells supposedly suppress locally an effective anti-tumor immune response within tumor tissues, although the precise mechanism by which T reg cells infiltrate the tumor is still unclear. We provide evidence that Neuropilin 1 (Nrp-1), highly expressed by Foxp3+ T reg cells, regulates the immunological anti-tumor control by guiding T reg cells into the tumor in response to tumor-derived vascular endothelial growth factor (VEGF). We demonstrate for the first time that T cell–specific ablation of Nrp-1 expression results in a significant breakdown in tumor immune escape in various transplantation models and in a spontaneous, endogenously driven melanoma model associated with strongly reduced tumor growth and prolonged tumor-free survival. Strikingly, numbers of tumor-infiltrating Foxp3+ T reg cells were significantly reduced accompanied by enhanced activation of CD8+ T cells within tumors of T cell–specific Nrp-1–deficient mice. This phenotype can be reversed by adoptive transfer of Nrp-1+ T reg cells from wild-type mice. Thus, our data strongly suggest that Nrp-1 acts as a key mediator of Foxp3+ T reg cell infiltration into the tumor site resulting in a dampened anti-tumor immune response and enhanced tumor progression. PMID:23045606

Interdependence of plant water status with photosynthetic performance and root defense responses in Vigna radiata (L.) Wilczek under progressive drought stress and recovery.

PubMed

Sengupta, Debashree; Guha, Anirban; Reddy, Attipalli Ramachandra

2013-10-05

The present study investigates the interdependence of plant water status with foliar and root responses in Vigna radiata L.Wilczek under progressive drought. Vegetatively-mature V. radiata plants were subjected to water withdrawal for 3 and 6days (D3 and D6, respectively) and then re-watered subsequently for 6days (6R) for stress-recovery. Changes in plant water status were expressed in terms of leaf and root moisture contents (LMC and RMC, respectively) and leaf relative water content (LRWC). Progressive drought caused apparent decrease in LRWC, LMC and RMC depicting significant level of dehydration of leaf and root tissues. Stomatal limitation alone could not account for the observed decrease in net CO2 assimilation rates (Pn) due to comparatively less decrease in sub-stomatal CO2 (Ci) concentrations with respect to other gas exchange parameters indicating possible involvement of non-stomatal limitations. Analysis of polyphasic chl a fluorescence kinetics during progressive drought showed decreased energy connectivity among PSII units as defined by a positive L-band with highest amplitude during D6. Efficiency of electron flux from OEC towards PSII acceptor side was not significantly affected during drought conditions as evidenced by the absence of a positive K-band. Increasing root-level water-limitation enforced a gradual oxidative stress through H2O2 accumulation and membrane lipid peroxidation in V. radiata roots exhibiting drastic enhancement of proline content and a significant but gradual increase in ascorbic acid content as well as guaiacol peroxidase activity under progressive drought. Expression analysis of Δ(1) pyrroline-5-carboxylate synthetase (P5CS) through real time PCR and enzyme activity studies showed a strong positive correlation between VrP5CS gene expression, enzyme activity and proline accumulation in the roots of V. radiata under progressive drought and recovery. Drought-induced changes in root moisture content (RMC) showed positive linear correlations with leaf water content, stomatal conductance as well as transpirational water loss dynamics and a significant negative correlation with the corresponding drought-induced expression patterns of ascorbate, guaiacol peroxidase and proline in roots of V. radiata. The study provides new insights into the plant water status-dependent interrelationship between photosynthetic performance and major root defense responses of V. radiata under progressive drought conditions. Copyright © 2013 Elsevier B.V. All rights reserved.

Combination of radiation therapy and firocoxib for the treatment of canine nasal carcinoma.

PubMed

Cancedda, Simona; Sabattini, Silvia; Bettini, Giuliano; Leone, Vito F; Laganga, Paola; Rossi, Federica; Terragni, Rossella; Gnudi, Giacomo; Vignoli, Massimo

2015-01-01

Carcinomas represent two-thirds of canine nasosinal neoplasms. Although radiation therapy (RT) is the standard of care, the incidence of local recurrence following treatment is high. Cyclooxygenase-isoform-2 (COX-2) is expressed in 71-95% of canine nasal carcinomas and has been implicated in tumor growth and angiogenesis. Accordingly, COX-2 inhibition seems rational to improve outcome. Dogs with histologically confirmed, previously untreated nasal carcinomas were randomized to receive the combination of a selective COX-2 inhibitor (firocoxib) and palliative RT (Group 1) or RT and placebo (Group 2). Patients were regularly monitored with blood tests, urinalysis, and computed tomography. Pet owners were asked to complete monthly a quality-of-life questionnaire. Twenty-four dogs were prospectively enrolled. According to Adams modified system, there were five stage 1, five stage 2, three stage 3, and 11 stage 4 tumors. Two dogs had metastases to regional lymph nodes. Median progression-free interval and overall survival were 228 and 335 days in Group 1 (n = 12) and 234 and 244 days in Group 2 (n = 12). These differences were not statistically significant. The involvement of regional lymph nodes was significantly associated with progression-free interval and overall survival (P = 0.004). Quality of life was significantly improved in Group 1 (P = 0.008). In particular, a significant difference was observed for activity and appetite. Although not providing a significant enhancement of progression-free interval and overall survival, firocoxib in combination with RT is safe and improved life quality in dogs with nasal carcinomas. © 2015 American College of Veterinary Radiology.

Immune-Inflammatory and Oxidative and Nitrosative Stress Biomarkers of Depression Symptoms in Subjects with Multiple Sclerosis: Increased Peripheral Inflammation but Less Acute Neuroinflammation.

PubMed

Kallaur, Ana Paula; Lopes, Josiane; Oliveira, Sayonara Rangel; Simão, Andrea Name Colado; Reiche, Edna Maria Vissoci; de Almeida, Elaine Regina Delicato; Morimoto, Helena Kaminami; de Pereira, Wildea Lice Carvalho Jennings; Alfieri, Daniele Frizon; Borelli, Sueli Donizete; Kaimen-Maciel, Domacio Ramon; Maes, Michael

2016-10-01

There is evidence that activated immune-inflammatory and oxidative and nitrosative stress (IO&NS) pathways play a role in the pathophysiology of multiple sclerosis (MS) and depression. This study examines serum levels of interleukin (IL)-1β, IL-4, IL-6, and IL-10; peroxides (LOOH); nitric oxide metabolites (NOx); albumin; ferritin; C-reactive protein (CRP); and tumor necrosis factor (TNF)-β NcoI polymorphism (rs909253) and gadolinium-enhanced magnetic resonance imaging (MRI) scan in MS patients with (n = 42) and without (n = 108) depression and normal controls (n = 249). Depression is scored using the depressive subscale of the Hospital Anxiety and Depression Scale (HADS). The extent of neurological disability is measured using the Expanded Disability Status Scale (EDSS) at the same time of the abovementioned measurements and 5 years earlier. Disease progression is assessed as actual EDSS-EDSS 5 years earlier. Three variables discriminate MS patients with depression from those without depression, i.e., increased IL-6 and lower IL-4 and albumin. Binary logistic regression showed that MS with depression (versus no depression) was characterized by more gastrointestinal symptoms and disease progression, higher serum IL-6, and lower albumin levels. In subjects with MS, the HADS score was significantly predicted by three EDSS symptoms, i.e., pyramidal, gastrointestinal, and visual symptoms. Fifty-eight percent of the variance in the HADS score was predicted by gastrointestinal symptoms, visual symptoms, the TNFB1/B2 genotype, and contrast enhancement (both inversely associated). There were no significant associations between depression in MS and type of MS, duration of illness, age, sex, nicotine dependence, and body mass index. MS with depression is associated with signs of peripheral inflammation, more disability, disease progression, gastrointestinal and visual symptoms, but less contrast enhancement as compared to MS without depression. It is concluded that depression is part of the neurological symptoms of MS and that its expression is primed by peripheral inflammation while acute neuroinflammation and the TNFB1/B2 genotype may be protective.

Progress in reading and spelling of dyslexic children is not affected by executive functioning.

PubMed

Walda, Sietske A E; van Weerdenburg, Marjolijn; Wijnants, Maarten L; Bosman, Anna M T

2014-12-01

Although poor reading and spelling skills have been associated with weak skills of executive functioning (EF), its role in literacy is not undisputed. Because EF has different theoretical underpinnings, methods of analysis and of assessing, it has led to varying and often contrasting results in its effects in children with dyslexia. The present study has two goals. The first goal is to establish the relationship between a large number of EF tasks and reading and spelling skills in a large number of Dutch dyslexic children (n = 229). More interesting, however, is the second aim. To what extent do EF skills predict progress in reading and spelling in dyslexic children who attended a remediation programme? The results revealed small, but significant relationships between EF and reading and spelling skills, but no relationships between EF and progress in reading and spelling. It is concluded that training EF skills is unlikely to enhance reading and spelling skills. Copyright © 2014 Elsevier Ltd. All rights reserved.

Highlights of Aeroacoustics Research in the U.S. 1998

NASA Technical Reports Server (NTRS)

Raman, Ganesh; McLaughlin, Dennis K.

1999-01-01

Highlights of aeroacoustics research in the United States of America during 1998 are reported in a summary compiled from information provided by members of the Aeroacoustics Technical Committee of the American Institute of Aeronautics and Astronautics (AIAA) and other leading research groups in industry, national laboratories, and academia. The past few years have seen significant progress in aeroacoustics. Research has steadily progressed toward enhanced safety, noise benefits, and lower costs. Since industrial progress is generally not published in the archival literature, it is particularly important to highlight these accomplishments. This year we chose to report on five topics of great interest to the aerospace industry including a synopsis of fundamental research at universities and national laboratories. The topics chosen are: (1) Advanced Subsonic Technology (AST), (2) High Speed Research (HSR), (3) Rotorcraft, (4) Weapons bay aeroacoustics control and (5) Academic research including Computational AeroAcoustics (CAA). Although the information presented in this review is not all encompassing we hope that the topics covered will provide some insights into aeroacoustics activity in the U.S.

Physical activity and cancer prevention : pathways and targets for intervention.

PubMed

Rogers, Connie J; Colbert, Lisa H; Greiner, John W; Perkins, Susan N; Hursting, Stephen D

2008-01-01

The prevalence of obesity, an established epidemiological risk factor for many cancers, has risen steadily for the past several decades in the US and many other countries. Particularly alarming are the increasing rates of obesity among children, portending continuing increases in the rates of obesity and obesity-related cancers for many years to come. Modulation of energy balance, via increased physical activity, has been shown in numerous comprehensive epidemiological reviews to reduce cancer risk. Unfortunately, the effects and mechanistic targets of physical activity interventions on the carcinogenesis process have not been thoroughly characterized. Studies to date suggest that exercise can exert its cancer-preventive effects at many stages during the process of carcinogenesis, including both tumour initiation and progression. As discussed in this review, exercise may be altering tumour initiation events by modifying carcinogen activation, specifically by enhancing the cytochrome P450 system and by enhancing selective enzymes in the carcinogen detoxification pathway, including, but not limited to, glutathione-S-transferases. Furthermore, exercise may reduce oxidative damage by increasing a variety of anti-oxidant enzymes, enhancing DNA repair systems and improving intracellular protein repair systems. In addition to altering processes related to tumour initiation, exercise may also exert a cancer-preventive effect by dampening the processes involved in the promotion and progression stages of carcinogenesis, including scavenging reactive oxygen species (ROS); altering cell proliferation, apoptosis and differentiation; decreasing inflammation; enhancing immune function; and suppressing angiogenesis. A paucity of data exists as to whether exercise may be working as an anti-promotion strategy via altering ROS in initiated or preneoplastic models; therefore, no conclusions can be made about this possible mechanism. The studies directly examining cell proliferation and apoptosis have shown that exercise can enhance both processes, which is difficult to interpret in the context of carcinogenesis. Studies examining the relationship between exercise and chronic inflammation suggest that exercise may reduce pro-inflammatory mediators and reduce the state of low-grade, chronic inflammation. Additionally, exercise has been shown to enhance components of the innate immune response (i.e. macrophage and natural killer cell function). Finally, only a limited number of studies have explored the relationship between exercise and angiogenesis; therefore, no conclusions can be made currently about the role of exercise in the angiogenesis process as it relates to tumour progression. In summary, exercise can alter biological processes that contribute to both anti-initiation and anti-progression events in the carcinogenesis process. However, more sophisticated, detailed studies are needed to examine each of the potential mechanisms contributing to an exercise-induced decrease in carcinogenesis in order to determine the minimum dose, duration and frequency of exercise needed to yield significant cancer-preventive effects, and whether exercise can be used prescriptively to reverse the obesity-induced physiological changes that increase cancer risk.

Comparing self-guided learning and educator-guided learning formats for simulation-based clinical training.

PubMed

Brydges, Ryan; Carnahan, Heather; Rose, Don; Dubrowski, Adam

2010-08-01

In this paper, we tested the over-arching hypothesis that progressive self-guided learning offers equivalent learning benefit vs. proficiency-based training while limiting the need to set proficiency standards. We have shown that self-guided learning is enhanced when students learn on simulators that progressively increase in fidelity during practice. Proficiency-based training, a current gold-standard training approach, requires achievement of a criterion score before students advance to the next learning level. Baccalaureate nursing students (n = 15/group) practised intravenous catheterization using simulators that differed in fidelity (i.e. students' perceived realism). Data were collected in 2008. Proficiency-based students advanced from low- to mid- to high-fidelity after achieving a proficiency criterion at each level. Progressive students self-guided their progression from low- to mid- to high-fidelity. Yoked control students followed an experimenter-defined progressive practice schedule. Open-ended students moved freely between the simulators. One week after practice, blinded experts evaluated students' skill transfer on a standardized patient simulation. Group differences were examined using analyses of variance. Proficiency-based students scored highest on the high-fidelity post-test (effect size = 1.22). An interaction effect showed that the Progressive and Open-ended groups maintained their performance from post-test to transfer test, whereas the Proficiency-based and Yoked control groups experienced a significant decrease (P < 0.05). Surprisingly, most Open-ended students (73%) chose the progressive practice schedule. Progressive training and proficiency-based training resulted in equivalent transfer test performance, suggesting that progressive students effectively self-guided when to transition between simulators. Students' preference for the progressive practice schedule indicates that educators should consider this sequence for simulation-based training.

Heme Oxygenase 1 as a Therapeutic Target in Acute Kidney Injury

PubMed Central

Bolisetty, Subhashini; Zarjou, Abolfazl; Agarwal, Anupam

2017-01-01

A common clinical condition, acute kidney injury (AKI) significantly influences morbidity and mortality, particularly in critically ill patients. The pathophysiology of AKI is complex and involves multiple pathways including inflammation, autophagy, cell cycle progression, and oxidative stress. Recent evidence suggests that a single insult to the kidney significantly enhances the propensity to develop chronic kidney disease. Therefore, generation of effective therapies against AKI are timely. In this context, the cytoprotective effects of heme oxygenase 1 (HO-1) in animal models of AKI are well documented. HO-1 modulates oxidative stress, autophagy, and inflammation, and regulates the progression of cell cycle via direct and indirect mechanisms. These beneficial effects of HO-1 induction during AKI are, in part, mediated by the by-products of the HO reaction (iron, carbon monoxide, and bile pigments). This review highlights the recent advances in the molecular mechanisms of HO-1–mediated cytoprotection and discusses the translational potential of HO-1 induction in AKI. PMID:28139396

SP-100 - The national space reactor power system program in response to future needs

NASA Astrophysics Data System (ADS)

Armijo, J. S.; Josloff, A. T.; Bailey, H. S.; Matteo, D. N.

The SP-100 system has been designed to meet comprehensive and demanding NASA/DOD/DOE requirements. The key requirements include: nuclear safety for all mission phases, scalability from 10's to 100's of kWe, reliable performance at full power for seven years of partial power for ten years, survivability in civil or military threat environments, capability to operate autonomously for up to six months, capability to protect payloads from excessive radiation, and compatibility with shuttle and expendable launch vehicles. The authors address of major progress in terms of design, flexibility/scalability, survivability, and development. These areas, with the exception of survivability, are discussed in detail. There has been significant improvement in the generic flight system design with substantial mass savings and simplification that enhance performance and reliability. Design activity has confirmed the scalability and flexibility of the system and the ability to efficiently meet NASA, AF, and SDIO needs. SP-100 development continues to make significant progress in all key technology areas.

HEPATIC LIPOGENESIS IN D$sub 2$O-FED MICE

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rabinowitz, J.L.; Defendi, V.; Langan, J.

1960-11-25

Swiss mice were maintained on a regimen of 25% D/sub 2/O for three weeks. The mice were slightly smaller than H/sub 2/O-fed controls, but the liver weight to body weight ratio was greater. There were no significant differences in liver lipid or cholesterol. Histologic examination showed progressive vacuolization and loss of basophilia, with changes in the mitochondrial distribution in the cytoplasm. These alterations did not show any specific localization in the hepatic lobule. There was a progressive reduction in the ability of liver homogenates from D/sub 2/O-fed mice to convert acetate-2-C-14 to cholesterol and fatty acid. Incubation of normal mousemore » livers in media containing 75% D/sub 2/O resulted in significant enhancement of cholestero1 and fatty acid biosynthetic capacity. This reduced lipogenesis in D/sub 2/O-fed mice appears to be due to derangements in cell structure, rather than to inhibition of enzyme activity. (auth)« less

Enhancements for a Dynamic Data Warehousing and Mining System for Large-Scale HSCB Data

DTIC Science & Technology

2016-04-21

Intelligent Automation Incorporated Enhancements for a Dynamic Data Warehousing and Mining ...Page | 2 Intelligent Automation Incorporated Progress Report No. 1 Enhancements for a Dynamic Data Warehousing and Mining System Large-Scale

Strengthening the HIV Care Continuum in the Dominican Republic: Application of a Triadic Implementation Framework to Meet the UNAIDS 90-90-90 Treatment Goal.

PubMed

Bowman, Alex S; Mehta, Mili; Lerebours Nadal, Leonel; Halpern, Mina; Nicholas, Stephen W; Amesty, Silvia

2017-10-01

Innovative empirical frameworks to evaluate progress in efforts addressing HIV treatment and prevention barriers in resource-limited areas are sorely needed to achieve the UNAIDS 90-90-90 goal (90% diagnosed, 90% on treatment, and 90% virally suppressed). A triadic implementation framework (TIF) is a comprehensive conceptual tool for (1) monitoring attrition, (2) evaluating operational programs, and (3) measuring the impact of specific implementation goals within the care continuum. TIF will assess the effects of enhanced programs on adherence and virologic suppression within the HIV care continuum at a regional clinic in the Dominican Republic (Clínica de Familia La Romana [CFLR]) and its program serving high-risk, migratory batey (sugarcane cultivation) communities. A retrospective cohort study completed during 2015 collected deidentified data from a CFLR chart review of adult HIV patients diagnosed in 2013. The results were quantitatively analyzed and compared to 2011 cohort data. In 2013, 310 patients were diagnosed HIV positive. The results demonstrated 73% enrolling in care, 28% adhering to care, and 16% achieving viral load suppression. Engagement increased across all steps of the care continuum compared to a 2011 cohort, culminating in a significant increase in undetectable viral load from 4% to 16% (p < 0.001). The batey program showed significant increases in patient enrollment compared to the 2011 cohort (p < 0.001). Meeting the UNAIDS 90-90-90 goal requires enhanced services in high-burden, resource-limited regions. CFLR employs TIF to assess progress and programmatic areas in need of strengthening. Data suggest enhanced CFLR services improve outcomes. Given improvements, maintenance and expansion of similar programs are warranted to achieve the 90-90-90 goal.

A preliminary study into the sensitivity of disease activity detection by serial weekly magnetic resonance imaging in multiple sclerosis.

PubMed Central

Lai, M; Hodgson, T; Gawne-Cain, M; Webb, S; MacManus, D; McDonald, W I; Thompson, A J; Miller, D H

1996-01-01

Long TR and gadolinium enhanced spin echo brain MRI was performed weekly for three months in three patients with relapsing-remitting or secondary progressive multiple sclerosis. During the study, 38 new enhancing lesions were seen; 11 showed enhancement for less than four weeks, and two enhanced on only one scan. All 16 new lesions seen on long TR scans showed initial enhancement. When only every fourth (monthly) scan was analysed, a total of 33 new enhancing lesions were seen. Subject to confirmation in a larger cohort, the results suggest: (a) that blood brain barrier leakage is an invariable event in new lesion development in relapsing-remitting and secondary progressive multiple sclerosis; (b) the small increase in sensitivity of weekly scanning does not justify its use in preference to monthly scanning when monitoring treatments. Images PMID:8609517

Plasmofluidics: Merging Light and Fluids at the Micro-/Nano-Scale

PubMed Central

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph

2016-01-01

Plasmofluidics is the synergistic integration of plasmonics and micro/nano fluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids, and precise manipulation via micro/nano fluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, we examine and categorize the most recent advances in plasmofluidics into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro-/nano-scale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. We conclude with our perspectives on the upcoming challenges, opportunities, and the possible future directions of the emerging field of plasmofluidics. PMID:26140612

Plasmofluidics: Merging Light and Fluids at the Micro-/Nanoscale.

PubMed

Wang, Mingsong; Zhao, Chenglong; Miao, Xiaoyu; Zhao, Yanhui; Rufo, Joseph; Liu, Yan Jun; Huang, Tony Jun; Zheng, Yuebing

2015-09-16

Plasmofluidics is the synergistic integration of plasmonics and micro/nanofluidics in devices and applications in order to enhance performance. There has been significant progress in the emerging field of plasmofluidics in recent years. By utilizing the capability of plasmonics to manipulate light at the nanoscale, combined with the unique optical properties of fluids and precise manipulation via micro/nanofluidics, plasmofluidic technologies enable innovations in lab-on-a-chip systems, reconfigurable photonic devices, optical sensing, imaging, and spectroscopy. In this review article, the most recent advances in plasmofluidics are examined and categorized into plasmon-enhanced functionalities in microfluidics and microfluidics-enhanced plasmonic devices. The former focuses on plasmonic manipulations of fluids, bubbles, particles, biological cells, and molecules at the micro/nanoscale. The latter includes technological advances that apply microfluidic principles to enable reconfigurable plasmonic devices and performance-enhanced plasmonic sensors. The article is concluded with perspectives on the upcoming challenges, opportunities, and possible future directions of the emerging field of plasmofluidics. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Telehealth Applications to Enhance CKD Knowledge and Awareness Among Patients and Providers.

PubMed

Tuot, Delphine S; Boulware, L Ebony

2017-01-01

CKD affects 13% of the US adult population, causes excess mortality, and is associated with significant sociodemographic disparities. Optimal CKD management slows progression of disease and reduces cardiovascular-related outcomes. Resources for patients and primary care providers, major stakeholders in preventive CKD care, are critically needed to enhance understanding of the disease and to optimize CKD health, particularly because of the asymptomatic nature of kidney disease. Telehealth is defined as the use of electronic communication and telecommunications technology to support long-distance clinical health care, patient and professional health-related education, and public health and health administration. It provides new opportunities to enhance awareness and understanding among these important stakeholders. This review will examine the role of telehealth within existing educational theories, identify telehealth applications that can enhance CKD knowledge and behavior change among patients and primary care providers, and examine the advantages and disadvantages of telehealth vs usual modalities for education. Copyright © 2016 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Contrast-enhanced ultrasound measurement of pancreatic blood flow dynamics predicts type 1 diabetes progression in preclinical models.

PubMed

St Clair, Joshua R; Ramirez, David; Passman, Samantha; Benninger, Richard K P

2018-05-01

In type 1 diabetes (T1D), immune-cell infiltration into the islets of Langerhans (insulitis) and β-cell decline occurs many years before diabetes clinically presents. Non-invasively detecting insulitis and β-cell decline would allow the diagnosis of eventual diabetes, and provide a means to monitor therapeutic intervention. However, there is a lack of validated clinical approaches for specifically and non-invasively imaging disease progression leading to T1D. Islets have a denser microvasculature that reorganizes during diabetes. Here we apply contrast-enhanced ultrasound measurements of pancreatic blood-flow dynamics to non-invasively and predictively assess disease progression in T1D pre-clinical models. STZ-treated mice, NOD mice, and adoptive-transfer mice demonstrate altered islet blood-flow dynamics prior to diabetes onset, consistent with islet microvasculature reorganization. These assessments predict both time to diabetes onset and future responders to antiCD4-mediated disease prevention. Thus contrast-enhanced ultrasound measurements of pancreas blood-flow dynamics may provide a clinically deployable predictive marker for disease progression in pre-symptomatic T1D and therapeutic reversal.

Sequential and direct ionic excitation in the strong-field ionization of 1-butene molecules.

PubMed

Schell, Felix; Boguslavskiy, Andrey E; Schulz, Claus Peter; Patchkovskii, Serguei; Vrakking, Marc J J; Stolow, Albert; Mikosch, Jochen

2018-05-18

We study the Strong-Field Ionization (SFI) of the hydrocarbon 1-butene as a function of wavelength using photoion-photoelectron covariance and coincidence spectroscopy. We observe a striking transition in the fragment-associated photoelectron spectra: from a single Above Threshold Ionization (ATI) progression for photon energies less than the cation D0-D1 gap to two ATI progressions for a photon energy greater than this gap. For the first case, electronically excited cations are created by SFI populating the ground cationic state D0, followed by sequential post-ionization excitation. For the second case, direct sub-cycle SFI to the D1 excited cation state contributes significantly. Our experiments access ionization dynamics in a regime where strong-field and resonance-enhanced processes can interplay.

Pneumonic Plague: The Darker Side of Yersinia pestis.

PubMed

Pechous, Roger D; Sivaraman, Vijay; Stasulli, Nikolas M; Goldman, William E

2016-03-01

Inhalation of the bacterium Yersinia pestis results in primary pneumonic plague. Pneumonic plague is the most severe manifestation of plague, with mortality rates approaching 100% in the absence of treatment. Its rapid disease progression, lethality, and ability to be transmitted via aerosol have compounded fears of the intentional release of Y. pestis as a biological weapon. Importantly, recent epidemics of plague have highlighted a significant role for pneumonic plague during outbreaks of Y. pestis infections. In this review we describe the characteristics of pneumonic plague, focusing on its disease progression and pathogenesis. The rapid time-course, severity, and difficulty of treating pneumonic plague highlight how differences in the route of disease transmission can enhance the lethality of an already deadly pathogen. Copyright © 2015 Elsevier Ltd. All rights reserved.

Enhanced M1 Macrophage Polarization in Human Helicobacter pylori-Associated Atrophic Gastritis and in Vaccinated Mice

PubMed Central

Quiding-Järbrink, Marianne; Raghavan, Sukanya; Sundquist, Malin

2010-01-01

Background Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. Methodology/Principal Findings By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. Conclusions/Significance These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis. PMID:21124899

Extracellular deoxyribonuclease made by group A Streptococcus assists pathogenesis by enhancing evasion of the innate immune response.

PubMed

Sumby, Paul; Barbian, Kent D; Gardner, Donald J; Whitney, Adeline R; Welty, Diane M; Long, R Daniel; Bailey, John R; Parnell, Michael J; Hoe, Nancy P; Adams, Gerald G; Deleo, Frank R; Musser, James M

2005-02-01

Many pathogenic bacteria produce extracellular DNase, but the benefit of this enzymatic activity is not understood. For example, all strains of the human bacterial pathogen group A Streptococcus (GAS) produce at least one extracellular DNase, and most strains make several distinct enzymes. Despite six decades of study, it is not known whether production of DNase by GAS enhances virulence. To test the hypothesis that extracellular DNase is required for normal progression of GAS infection, we generated seven isogenic mutant strains in which the three chromosomal- and prophage-encoded DNases made by a contemporary serotype M1 GAS strain were inactivated. Compared to the wild-type parental strain, the isogenic triple-mutant strain was significantly less virulent in two mouse models of invasive infection. The triple-mutant strain was cleared from the skin injection site significantly faster than the wild-type strain. Preferential clearance of the mutant strain was related to the differential extracellular killing of the mutant and wild-type strains, possibly through degradation of neutrophil extracellular traps, innate immune structures composed of chromatin and granule proteins. The triple-mutant strain was also significantly compromised in its ability to cause experimental pharyngeal disease in cynomolgus macaques. Comparative analysis of the seven DNase mutant strains strongly suggested that the prophage-encoded SdaD2 enzyme is the major DNase that contributes to virulence in this clone. We conclude that extracellular DNase activity made by GAS contributes to disease progression, thereby resolving a long-standing question in bacterial pathogenesis research.

Atypical magnetic resonance imaging features in subacute sclerosing panencephalitis

PubMed Central

Das, Biplab; Goyal, Manoj Kumar; Modi, Manish; Mehta, Sahil; Chakravarthi, Sudheer; Lal, Vivek; Vyas, Sameer

2016-01-01

Objectives: Subacute sclerosing panencephalitis (SSPE) is rare chronic, progressive encephalitis that affects primarily children and young adults, caused by a persistent infection with measles virus. No cure for SSPE exists, but the condition can be managed by medication if treatment is started at an early stage. Methods and Results: Heterogeneity of imaging findings in SSPE is not very uncommon. But pial and gyral enhancements are very rarely noticed. Significant asymmetric onset as well as pial-gyral enhancements is not reported. Herein we present a case of 16 years adolescent of SSPE having remarkable asymmetric pial-gyral enhancements, which were misinterpreted as tubercular infection. Conclusion: Early diagnosis and treatment is encouraging in SSPE, although it is not curable with current therapy. Clinico-radiological and electrophysiological correlation is very important in diagnosis of SSPE, more gravely in patients having atypical image findings as in our index case. PMID:27293348

Enhancing promotional strategies within social marketing programs: use of Web 2.0 social media.

PubMed

Thackeray, Rosemary; Neiger, Brad L; Hanson, Carl L; McKenzie, James F

2008-10-01

The second generation of Internet-based applications (i.e., Web 2.0), in which users control communication, holds promise to significantly enhance promotional efforts within social marketing campaigns. Web 2.0 applications can directly engage consumers in the creative process by both producing and distributing information through collaborative writing, content sharing, social networking, social bookmarking, and syndication. Web 2.0 can also enhance the power of viral marketing by increasing the speed at which consumers share experiences and opinions with progressively larger audiences. Because of the novelty and potential effectiveness of Web 2.0, social marketers may be enticed to prematurely incorporate related applications into promotional plans. However, as strategic issues such as priority audience preferences, selection of appropriate applications, tracking and evaluation, and related costs are carefully considered, Web 2.0 will expand to allow health promotion practitioners more direct access to consumers with less dependency on traditional communication channels.

Exploring the experiences and coping strategies of international medical students

PubMed Central

2011-01-01

Background Few studies have addressed the challenges that international medical students face and there is a dearth of information on the behavioural strategies these students adopt to successfully progress through their academic program in the face of substantial difficulties of language barrier, curriculum overload, financial constraints and assessment tasks that require high proficiency in communication skills. Methods This study was designed primarily with the aim of enhancing understanding of the coping strategies, skill perceptions and knowledge of assessment expectations of international students as they progress through the third and fourth years of their medical degree at the School of Medicine, University of Tasmania, Australia. Results Survey, focus group discussion and individual interviews revealed that language barriers, communication skills, cultural differences, financial burdens, heavy workloads and discriminatory bottlenecks were key factors that hindered their adaptation to the Australian culture. Quantitative analyses of their examination results showed that there were highly significant (p < 0.001) variations between student performances in multiple choice questions, short answer questions and objective structured clinical examinations (70.3%, 49.7% & 61.7% respectively), indicating existence of communication issues. Conclusions Despite the challenges, these students have adopted commendable coping strategies and progressed through the course largely due to their high sense of responsibility towards their family, their focus on the goal of graduating as medical doctors and their support networks. It was concluded that faculty needs to provide both academic and moral support to their international medical students at three major intervention points, namely point of entry, mid way through the course and at the end of the course to enhance their coping skills and academic progression. Finally, appropriate recommendations were made. PMID:21702988

Connected Health and Progress against Cancer

Cancer.gov

An NCI Cancer Currents blog post about a new report from President’s Cancer Panel outlining how connective technologies can promote cancer prevention, enhance patients’ treatment experience, and accelerate progress in cancer research.

Novel Coatings for Enhancement of Light-Emitting Diodes (LEDs)

DTIC Science & Technology

2006-10-28

quantum efficiency of LEDs. SAIC’s strength is this area is a proprietary nonimaging optics code. In consultation with Lumileds, SAIC developed designs for...five different optical ele- ments that collect and project light from a LED. The simulations showed that the designs achieve a significant improvement... optical microscope at 100x power the coating is not visible. Fire sample 6DecO4P1 in tube furnace As a first test, sample 6Dec04P1 was progressively

Analysis of ERTS-1 imagery of Wyoming and its application to evaluation of Wyoming's natural resources

NASA Technical Reports Server (NTRS)

Marrs, R. W.; Breckenridge, R. M.

1973-01-01

The author has identified the following significant results. The Wyoming investigation has progressed according to schedule during the Jan. - Feb., 1973 report period. A map of the maximum extent of Pleistocene glaciation was compiled for northwest Wyoming from interpretations of glacial features seen on ERTS-1 imagery. Using isodensitometry as a tool for image enhancement, techniques were developed which allowed accurate delineation of small urban areas and provided distinction of broad classifications within these small urban centers.

Role of cholesterol and lipid organization in disease

NASA Astrophysics Data System (ADS)

Maxfield, Frederick R.; Tabas, Ira

2005-12-01

Membrane lipids are essential for biological functions ranging from membrane trafficking to signal transduction. The composition of lipid membranes influences their organization and properties, so it is not surprising that disorders in lipid metabolism and transport have a role in human disease. Significant recent progress has enhanced our understanding of the molecular and cellular basis of lipid-associated disorders such as Tangier disease, Niemann-Pick disease type C and atherosclerosis. These insights have also led to improved understanding of normal physiology.

Evolution of ferromagnetism in charge ordered manganite: An effect of external pressure

NASA Astrophysics Data System (ADS)

Dash, S.; Pradhan, M. K.; Rao, T. Lakshmana

2018-05-01

Detailed magnetic measurements of the Pr0.75Na0.25MnO3 polycrystalline sample have been carried out under external hydrostatic pressure upto 10kbar. Pressure strongly suppresses the first order magnetic transition, while thermal hysteresis narrows down progressively and then disappears with increase in pressure. The significant enhancement of the field cooled magnetization value at different pressures is due to the antiferromagnetic to ferromagnetic transformation, while ruling out any contribution from the domain alignment within the ferromagnetic phase.

Inflammation disrupts the LDL receptor pathway and accelerates the progression of vascular calcification in ESRD patients.

PubMed

Liu, Jing; Ma, Kun Ling; Gao, Min; Wang, Chang Xian; Ni, Jie; Zhang, Yang; Zhang, Xiao Liang; Liu, Hong; Wang, Yan Li; Liu, Bi Cheng

2012-01-01

Chronic inflammation plays a crucial role in the progression of vascular calcification (VC). This study was designed to investigate whether the low-density lipoprotein receptor (LDLr) pathway is involved in the progression of VC in patients with end-stage renal disease (ESRD) during inflammation. Twenty-eight ESRD patients were divided into control and inflamed groups according to plasma C-reactive protein (CRP) level. Surgically removed tissues from the radial arteries of patients receiving arteriovenostomy were used in the experiments. The expression of tumour necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) of the radial artery were increased in the inflamed group. Hematoxylin-eosin and alizarin red S staining revealed parallel increases in foam cell formation and calcium deposit formation in continuous cross-sections of radial arteries in the inflamed group compared to the control, which were closely correlated with increased LDLr, sterol regulatory element binding protein-2 (SREBP-2), bone morphogenetic proteins-2 (BMP-2), and collagen I protein expression, as shown by immunohistochemical and immunofluorescent staining. Confocal microscopy confirmed that inflammation enhanced the translocation of the SREBP cleavage-activating protein (SCAP)/SREBP-2 complex from the endoplasmic reticulum to the Golgi, thereby activating LDLr gene transcription. Inflammation increased alkaline phosphatase protein expression and reduced α-smooth muscle actin protein expression, contributing to the conversion of the vascular smooth muscle cells in calcified vessels from the fibroblastic to the osteogenic phenotype; osteogenic cells are the main cellular components involved in VC. Further analysis showed that the inflammation-induced disruption of the LDLr pathway was significantly associated with enhanced BMP-2 and collagen I expression. Inflammation accelerated the progression of VC in ESRD patients by disrupting the LDLr pathway, which may represent a novel mechanism involved in the progression of both VC and atherosclerosis.

Dynamic Contrast-Enhanced MRI of Cervical Cancers: Temporal Percentile Screening of Contrast Enhancement Identifies Parameters for Prediction of Chemoradioresistance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, Erlend K.F.; Hole, Knut Hakon; Lund, Kjersti V.

Purpose: To systematically screen the tumor contrast enhancement of locally advanced cervical cancers to assess the prognostic value of two descriptive parameters derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). Methods and Materials: This study included a prospectively collected cohort of 81 patients who underwent DCE-MRI with gadopentetate dimeglumine before chemoradiotherapy. The following descriptive DCE-MRI parameters were extracted voxel by voxel and presented as histograms for each time point in the dynamic series: normalized relative signal increase (nRSI) and normalized area under the curve (nAUC). The first to 100th percentiles of the histograms were included in a log-rank survival test,more » resulting in p value and relative risk maps of all percentile-time intervals for each DCE-MRI parameter. The maps were used to evaluate the robustness of the individual percentile-time pairs and to construct prognostic parameters. Clinical endpoints were locoregional control and progression-free survival. The study was approved by the institutional ethics committee. Results: The p value maps of nRSI and nAUC showed a large continuous region of percentile-time pairs that were significantly associated with locoregional control (p < 0.05). These parameters had prognostic impact independent of tumor stage, volume, and lymph node status on multivariate analysis. Only a small percentile-time interval of nRSI was associated with progression-free survival. Conclusions: The percentile-time screening identified DCE-MRI parameters that predict long-term locoregional control after chemoradiotherapy of cervical cancer.« less

Progress and prospects of GaN-based LEDs using nanostructures

NASA Astrophysics Data System (ADS)

Zhao, Li-Xia; Yu, Zhi-Guo; Sun, Bo; Zhu, Shi-Chao; An, Ping-Bo; Yang, Chao; Liu, Lei; Wang, Jun-Xi; Li, Jin-Min

2015-06-01

Progress with GaN-based light emitting diodes (LEDs) that incorporate nanostructures is reviewed, especially the recent achievements in our research group. Nano-patterned sapphire substrates have been used to grow an AlN template layer for deep-ultraviolet (DUV) LEDs. One efficient surface nano-texturing technology, hemisphere-cones-hybrid nanostructures, was employed to enhance the extraction efficiency of InGaN flip-chip LEDs. Hexagonal nanopyramid GaN-based LEDs have been fabricated and show electrically driven color modification and phosphor-free white light emission because of the linearly increased quantum well width and indium incorporation from the shell to the core. Based on the nanostructures, we have also fabricated surface plasmon-enhanced nanoporous GaN-based green LEDs using AAO membrane as a mask. Benefitting from the strong lateral SP coupling as well as good electrical protection by a passivation layer, the EL intensity of an SP-enhanced nanoporous LED was significantly enhanced by 380%. Furthermore, nanostructures have been used for the growth of GaN LEDs on amorphous substrates, the fabrication of stretchable LEDs, and for increasing the 3-dB modulation bandwidth for visible light communication. Project supported by the National Natural Science Foundation of China (Grant No. 61334009), the National High Technology Research and Development Program of China (Grant Nos. 2015AA03A101 and 2014BAK02B08), China International Science and Technology Cooperation Program (Grant No. 2014DFG62280), the “Import Outstanding Technical Talent Plan” and “Youth Innovation Promotion Association Program” of the Chinese Academy of Sciences.

Nicotine enhancement and reinforcer devaluation: Interaction with opioid receptors.

PubMed

Kirshenbaum, Ari P; Suhaka, Jesse A; Phillips, Jessie L; Voltolini de Souza Pinto, Maiary

In rats, nicotine enhances responding maintained by non-pharmacological reinforcers, and discontinuation of nicotine devalues those same reinforcers. The goal of this study was to assess the interaction of nicotine and opioid receptors and to evaluate the degree to which nicotine enhancement and nicotine-induced devaluation are related to opioid activation. Nicotine (0.4mg/kg), or nicotine plus naloxone (0.3 or 3.0mg/kg), was delivered to rats prior to progressive ratio (PR) schedule sessions in which sucrose was used as a reinforcer. PR-schedule responding was assessed during ten daily sessions of drug delivery, and for three post-dosing days/sessions. Control groups for this investigation included a saline-only condition, and naloxone-only (0.3 or 3.0mg/kg) conditions. When administered in conjunction with nicotine, both naloxone doses attenuated nicotine enhancement of the sucrose reinforcer, and the combination of the larger dose of naloxone (3.0mg/kg) with nicotine produced significant impairments in sucrose reinforced responding. When administered alone, neither dose of naloxone (0.3 & 3.0mg/kg) significantly altered responding in comparison to saline. Furthermore, when dosing was discontinued after ten once-daily doses, all nicotine groups (nicotine-only and nicotine+naloxone combination) demonstrated significant decreases in sucrose reinforcement compared to the saline group. Although opioid antagonism attenuated reinforcement enhancement by nicotine, it did not prevent reinforcer devaluation upon discontinuation of nicotine dosing, and the higher dose of naloxone (3.0mg/kg) produced decrements upon discontinuation on its own in the absence of nicotine. Copyright © 2016 Elsevier Inc. All rights reserved.

Progress and challenges in bioinformatics approaches for enhancer identification

PubMed Central

Kleftogiannis, Dimitrios; Kalnis, Panos

2016-01-01

Enhancers are cis-acting DNA elements that play critical roles in distal regulation of gene expression. Identifying enhancers is an important step for understanding distinct gene expression programs that may reflect normal and pathogenic cellular conditions. Experimental identification of enhancers is constrained by the set of conditions used in the experiment. This requires multiple experiments to identify enhancers, as they can be active under specific cellular conditions but not in different cell types/tissues or cellular states. This has opened prospects for computational prediction methods that can be used for high-throughput identification of putative enhancers to complement experimental approaches. Potential functions and properties of predicted enhancers have been catalogued and summarized in several enhancer-oriented databases. Because the current methods for the computational prediction of enhancers produce significantly different enhancer predictions, it will be beneficial for the research community to have an overview of the strategies and solutions developed in this field. In this review, we focus on the identification and analysis of enhancers by bioinformatics approaches. First, we describe a general framework for computational identification of enhancers, present relevant data types and discuss possible computational solutions. Next, we cover over 30 existing computational enhancer identification methods that were developed since 2000. Our review highlights advantages, limitations and potentials, while suggesting pragmatic guidelines for development of more efficient computational enhancer prediction methods. Finally, we discuss challenges and open problems of this topic, which require further consideration. PMID:26634919

Nanoparticle Approaches against Bacterial Infections

PubMed Central

Gao, Weiwei; Thamphiwatana, Soracha; Angsantikul, Pavimol; Zhang, Liangfang

2014-01-01

Despite the wide success of antibiotics, the treatment of bacterial infection still faces significant challenges, particularly the emergence of antibiotic resistance. As a result, nanoparticle drug delivery platforms including liposomes, polymeric nanoparticles, dendrimers, and various inorganic nanoparticles have been increasingly exploited to enhance the therapeutic effectiveness of existing antibiotics. This review focuses on areas where nanoparticle approaches hold significant potential to advance the treatment of bacterial infection. These areas include targeted antibiotic delivery, environmentally responsive antibiotic delivery, combinatorial antibiotic delivery, nanoparticle-enabled antibacterial vaccination, and nanoparticle-based bacterial detection. In each area we highlight the innovative antimicrobial nanoparticle platforms and review their progress made against bacterial infections. PMID:25044325

Equity in health care financing in Palestine: the value-added of the disaggregate approach.

PubMed

Abu-Zaineh, Mohammad; Mataria, Awad; Luchini, Stéphane; Moatti, Jean-Paul

2008-06-01

This paper analyzes the redistributive effect and progressivity associated with the current health care financing schemes in the Occupied Palestinian Territory, using data from the first Palestinian Household Health Expenditure Survey conducted in 2004. The paper goes beyond the commonly used "aggregate summary index approach" to apply a more detailed "disaggregate approach". Such an approach is borrowed from the general economic literature on taxation, and examines redistributive and vertical effects over specific parts of the income distribution, using the dominance criterion. In addition, the paper employs a bootstrap method to test for the statistical significance of the inequality measures. While both the aggregate and disaggregate approaches confirm the pro-rich and regressive character of out-of-pocket payments, the aggregate approach does not ascertain the potential progressive feature of any of the available insurance schemes. The disaggregate approach, however, significantly reveals a progressive aspect, for over half of the population, of the government health insurance scheme, and demonstrates that the regressivity of the out-of-pocket payments is most pronounced among the worst-off classes of the population. Recommendations are advanced to improve the performance of the government insurance schemes to enhance its capacity in limiting inequalities in health care financing in the Occupied Palestinian Territory.

The Physiological/Pathophysiological Significance of Vitamin D in Cancer, Cardiovascular Disorders and Beyond.

PubMed

AlMatar, Manaf; AlMandeal, Husam; Makky, Essam A; Kayar, Begum; Yarar, Emel; Var, Isıl; Koksal, Fatih

2017-01-01

Vitamin D, a molecular precursor of the potent steroid hormone calcitriol, has crucial functions and roles in physiology and pathophysiology. Tellingly, calcitriol has been shown to regulate various cellular signalling networks and cascades that have crucial role in cancer biology and diagnostics. Mounting lines of evidences from previous clinical and preclinical investigations indicate that the deficiency of vitamin D may contribute to the carcinogenesis risk. Concomitantly, recent reports suggested that significant reduction in the cancer occurrence and progression is more likely to appear after vitamin D supplementation. Furthermore, a pivotal role functioned by vitamin D in cardiovascular physiology indicates that the deficiency of vitamin D is significantly correlated with enhanced prevalence of stroke, hypertension and myocardial infarction. Notably, vitamin D status is more likely to be used as a lifestyle biomarker, since poor and unhealthy lifestyles are correlated with the deficiency of vitamin D, a feature which may result in cardiovascular complications. Moreover, recent reports revealed that the effect of vitamin D is to cover not only cardiovascular system but also skeletal system. Herein, we are highlighting the recent knowledge of vitamin D roles and functions with respect to pathophysiological disorders such as cancer, cardiovascular diseases, rheumatoid arthritis (RA) and debate the potential avails of vitamin D on slowing cancer, cardiovascular disease and RA progression. The findings of this review confirm that the importance of vitamin D metabolites or analogues which can provide a helpful platform to target some kinds of cancer, particularly when used in combination with existing therapies. Moreover, the correlation between vitamin D deficiencies with cardiovascular diseases and rheumatoid arthritis (RA) progression might suggest a pivotal role of vitamin D in either initiation or progression of these diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Losartan Slows Pancreatic Tumor Progression and Extends Survival of SPARC-Null Mice by Abrogating Aberrant TGFβ Activation

PubMed Central

Arnold, Shanna A.; Rivera, Lee B.; Carbon, Juliet G.; Toombs, Jason E.; Chang, Chi-Lun; Bradshaw, Amy D.; Brekken, Rolf A.

2012-01-01

Pancreatic adenocarcinoma, a desmoplastic disease, is the fourth leading cause of cancer-related death in the Western world due, in large part, to locally invasive primary tumor growth and ensuing metastasis. SPARC is a matricellular protein that governs extracellular matrix (ECM) deposition and maturation during tissue remodeling, particularly, during wound healing and tumorigenesis. In the present study, we sought to determine the mechanism by which lack of host SPARC alters the tumor microenvironment and enhances invasion and metastasis of an orthotopic model of pancreatic cancer. We identified that levels of active TGFβ1 were increased significantly in tumors grown in SPARC-null mice. TGFβ1 contributes to many aspects of tumor development including metastasis, endothelial cell permeability, inflammation and fibrosis, all of which are altered in the absence of stromal-derived SPARC. Given these results, we performed a survival study to assess the contribution of increased TGFβ1 activity to tumor progression in SPARC-null mice using losartan, an angiotensin II type 1 receptor antagonist that diminishes TGFβ1 expression and activation in vivo. Tumors grown in SPARC-null mice progressed more quickly than those grown in wild-type littermates leading to a significant reduction in median survival. However, median survival of SPARC-null animals treated with losartan was extended to that of losartan-treated wild-type controls. In addition, losartan abrogated TGFβ induced gene expression, reduced local invasion and metastasis, decreased vascular permeability and altered the immune profile of tumors grown in SPARC-null mice. These data support the concept that aberrant TGFβ1-activation in the absence of host SPARC contributes significantly to tumor progression and suggests that SPARC, by controlling ECM deposition and maturation, can regulate TGFβ availability and activation. PMID:22348081

Aircraft family design using enhanced collaborative optimization

NASA Astrophysics Data System (ADS)

Roth, Brian Douglas

Significant progress has been made toward the development of multidisciplinary design optimization (MDO) methods that are well-suited to practical large-scale design problems. However, opportunities exist for further progress. This thesis describes the development of enhanced collaborative optimization (ECO), a new decomposition-based MDO method. To support the development effort, the thesis offers a detailed comparison of two existing MDO methods: collaborative optimization (CO) and analytical target cascading (ATC). This aids in clarifying their function and capabilities, and it provides inspiration for the development of ECO. The ECO method offers several significant contributions. First, it enhances communication between disciplinary design teams while retaining the low-order coupling between them. Second, it provides disciplinary design teams with more authority over the design process. Third, it resolves several troubling computational inefficiencies that are associated with CO. As a result, ECO provides significant computational savings (relative to CO) for the test cases and practical design problems described in this thesis. New aircraft development projects seldom focus on a single set of mission requirements. Rather, a family of aircraft is designed, with each family member tailored to a different set of requirements. This thesis illustrates the application of decomposition-based MDO methods to aircraft family design. This represents a new application area, since MDO methods have traditionally been applied to multidisciplinary problems. ECO offers aircraft family design the same benefits that it affords to multidisciplinary design problems. Namely, it simplifies analysis integration, it provides a means to manage problem complexity, and it enables concurrent design of all family members. In support of aircraft family design, this thesis introduces a new wing structural model with sufficient fidelity to capture the tradeoffs associated with component commonality, but of appropriate fidelity for aircraft conceptual design. The thesis also introduces a new aircraft family concept. Unlike most families, the intent is not necessarily to produce all family members. Rather, the family includes members for immediate production and members that address potential future market conditions and/or environmental regulations. The result is a set of designs that yield a small performance penalty today in return for significant future flexibility to produce family members that respond to new market conditions and environmental regulations.

Novel cross-talk between IGF-IR and DDR1 regulates IGF-IR trafficking, signaling and biological responses

PubMed Central

Sacco, Antonella; Morcavallo, Alaide; Vella, Veronica; Voci, Concetta; Spatuzza, Michela; Xu, Shi-Qiong; Iozzo, Renato V.; Vigneri, Riccardo; Morrione, Andrea; Belfiore, Antonino

2015-01-01

The insulin-like growth factor-I receptor (IGF-IR), plays a key role in regulating mammalian development and growth, and is frequently deregulated in cancer contributing to tumor initiation and progression. Discoidin domain receptor 1 (DDR1), a collagen receptor tyrosine-kinase, is as well frequently overexpressed in cancer and implicated in cancer progression. Thus, we investigated whether a functional cross-talk between the IGF-IR and DDR1 exists and plays any role in cancer progression. Using human breast cancer cells we found that DDR1 constitutively associated with the IGF-IR. However, this interaction was enhanced by IGF-I stimulation, which promoted rapid DDR1 tyrosine-phosphorylation and co-internalization with the IGF-IR. Significantly, DDR1 was critical for IGF-IR endocytosis and trafficking into early endosomes, IGF-IR protein expression and IGF-I intracellular signaling and biological effects, including cell proliferation, migration and colony formation. These biological responses were inhibited by DDR1 silencing and enhanced by DDR1 overexpression. Experiments in mouse fibroblasts co-transfected with the human IGF-IR and DDR1 gave similar results and indicated that, in the absence of IGF-IR, collagen-dependent phosphorylation of DDR1 is impaired. These results demonstrate a critical role of DDR1 in the regulation of IGF-IR action, and identify DDR1 as a novel important target for breast cancers that overexpress IGF-IR. PMID:25840417

Chronic Nerve Compression Accelerates the Progression of Diabetic Peripheral Neuropathy in a Rat Model: A Study of Gene Expression Profiling.

PubMed

Tu, Yiji; Chen, Zenggan; Hu, Junda; Ding, Zuoyou; Lineaweaver, William C; Dellon, A Lee; Zhang, Feng

2018-04-25

 This article investigates the role of chronic nerve compression in the progression of diabetic peripheral neuropathy (DPN) by gene expression profiling.  Chronic nerve compression was created in streptozotocin (STZ)-induced diabetic rats by wrapping a silicone tube around the sciatic nerve (SCN). Neurological deficits were evaluated using pain threshold test, motor nerve conduction velocity (MNCV), and histopathologic examination. Differentially expressed genes (DGEs) and metabolic processes associated with chronic nerve compression were analyzed.  Significant changes in withdrawal threshold and MNCV were observed in diabetic rats 6 weeks after diabetes induction, and in DPN rats 4 weeks after diabetes induction. Histopathologic examination of the SCN in DPN rats presented typical changes of myelin degeneration in DPN. Function analyses of DEGs demonstrated that biological processes related to inflammatory response, extracellular matrix component, and synaptic transmission were upregulated after diabetes induction, and chronic nerve compression further enhanced those changes. While processes related to lipid and glucose metabolism, response to insulin, and apoptosis regulation were inhibited after diabetes induction, chronic nerve compression further enhanced these inhibitions.  Our study suggests that additional silicone tube wrapping on the SCN of rat with diabetes closely mimics the course and pathologic findings of human DPN. Further studies are needed to verify the effectiveness of this rat model of DPN and elucidate the roles of the individual genes in the progression of DPN. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

PubMed

Liu, Chuanxia; Feng, Xiaoxia; Wang, Baixiang; Wang, Xinhua; Wang, Chaowei; Yu, Mengfei; Cao, Guifen; Wang, Huiming

2018-03-01

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

The potentiality of Trichoderma harzianum in alleviation the adverse effects of salinity in faba bean plants.

PubMed

Abd El-Baki, G K; Mostafa, Doaa

2014-12-01

The interaction between sodium chloride and Trichoderma harzianum (T24) on growth parameters, ion contents, MDA content, proline, soluble proteins as well as SDS page protein profile were studied in Vicia faba Giza 429. A sharp reduction was found in fresh and dry mass of shoots and roots with increasing salinity. Trichoderma treatments promoted the growth criteria as compared with corresponding salinized plants. The water content and leaf area exhibited a marked decrease with increasing salinity. Trichoderma treatments induced a progressive increase in both parameters. Both proline and MDA contents were increased progressively as the salinity rose in the soil. Trichoderma treatments considerably retarded the accumulation of both parameters in shoots and roots. Both Na+ and K+ concentration increased in both organs by enhancing salinity levels. The treatment with Trichoderma harzianum enhanced the accumulation of both ions. Exposure of plants to different concentrations of salinity, or others treated with Trichoderma harzianum produced marked changes in their protein pattern. Three types of alterations were observed: the synthesis of certain proteins declined significantly, specific synthesis of certain other proteins were markedly observed and synthesis of a set specific protein was induced de novo in plant treated with Trichoderma harzianum.

MIF induces osteoclast differentiation and contributes to progression of periodontal disease in mice.

PubMed

Madeira, Mila Fernandes Moreira; Queiroz-Junior, Celso Martins; Costa, Graciela Mitre; Santos, Patrícia Campi; Silveira, Elcia Maria; Garlet, Gustavo Pompermaier; Cisalpino, Patrícia Silva; Teixeira, Mauro Martins; Silva, Tarcília Aparecida; Souza, Daniele da Glória

2012-02-01

Periodontal disease (PD) is a chronic inflammatory and alveolar bone destructive disease triggered by microorganisms from the oral biofilm. Oral inoculation of mice with the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) induces marked alveolar bone loss and local production of inflammatory mediators, including Macrophage Migration Inhibitory Factor (MIF). The role of MIF for alveolar bone resorption during PD is not known. In the present study, experimental PD was induced in BALB/c wild-type mice (WT) and MIF knockout mice (MIF⁻/⁻) through oral inoculation of Aa. Despite enhanced number of bacteria, MIF⁻/⁻ mice had reduced infiltration of TRAP-positive cells and reduced alveolar bone loss. This was associated with decreased neutrophil accumulation and increased levels of IL-10 in periodontal tissues. TNF-α production was similar in both groups. In vitro, LPS from Aa enhanced osteoclastic activity in a MIF-dependent manner. In conclusion, MIF has role in controlling bacterial growth in the context of PD but contributes more significantly to the progression of bone loss during PD by directly affecting differentiation and activity of osteoclasts. Copyright © 2011 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Microneedles for intradermal and transdermal delivery

PubMed Central

Tuan-Mahmood, Tuan-Mazlelaa; McCrudden, Maeliosa T.C.; Torrisi, Barbara M.; McAlister, Emma; Garland, Martin J; Singh, Thakur Raghu Raj; Donnelly, Ryan F

2014-01-01

The formidable barrier properties of the uppermost layer of the skin, the stratum corneum impose significant limitations for successful systemic delivery of a broad range of therapeutic molecules, particularly macromolecules and genetic material. Microneedle delivery has been proposed as a strategy to breach the SC barrier function in order to facilitate effective transport of molecules across the skin. This strategy involves the use of micron sized needles fabricated from different materials and using different geometries to create transient aqueous conduits across the skin. Microneedles in isolation, or in combination with other enhancing strategies, have been shown to dramatically enhance the skin permeability of numerous therapeutic molecules including biopharmaceuticals either in vitro, ex vivo or in vivo. Progress in the areas of microneedle design, development and manufacture have proven promising in terms of the potential use of this emerging delivery method in clinical applications such as insulin delivery, transcutaneous immunisations and cutaneous gene delivery. This review article focuses on recent and potential future developments in microneedle technologies. This will include the detailing of progress made in microneedle design, an exploration of the challenges faced in this field and potential forward strategies to embrace the exploitation of microneedle methodologies, while considering the inherent safety aspects of such therapeutic tools. PMID:23680534

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeung, Timothy P C; Robarts Research Institute, The University of Western Ontario, Ontario, Canada, N6A 5B7; Department of Medical Biophysics, The University of Western Ontario, Ontario, Canada, N6A 5C1

Introduction: This study aimed to explore the potential for computed tomography (CT) perfusion and 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) in predicting sites of future progressive tumour on a voxel-by-voxel basis after radiotherapy and chemotherapy. Methods: Ten patients underwent pre-radiotherapy magnetic resonance (MR), FDG-PET and CT perfusion near the end of radiotherapy and repeated post-radiotherapy follow-up MR scans. The relationships between these images and tumour progression were assessed using logistic regression. Cross-validation with receiver operating characteristic (ROC) analysis was used to assess the value of these images in predicting sites of tumour progression. Results: Pre-radiotherapy MR-defined gross tumour; near-end-of-radiotherapy CT-defined enhancingmore » lesion; CT perfusion blood flow (BF), blood volume (BV) and permeability-surface area (PS) product; FDG-PET standard uptake value (SUV); and SUV:BF showed significant associations with tumour progression on follow-up MR imaging (P < 0.0001). The mean sensitivity (±standard deviation), specificity and area under the ROC curve (AUC) of PS were 0.64 ± 0.15, 0.74 ± 0.07 and 0.72 ± 0.12 respectively. This mean AUC was higher than that of the pre-radiotherapy MR-defined gross tumour and near-end-of-radiotherapy CT-defined enhancing lesion (both AUCs = 0.6 ± 0.1, P ≤ 0.03). The multivariate model using BF, BV, PS and SUV had a mean AUC of 0.8 ± 0.1, but this was not significantly higher than the PS only model. Conclusion: PS is the single best predictor of tumour progression when compared to other parameters, but voxel-based prediction based on logistic regression had modest sensitivity and specificity.« less

Minimising Same Error Repetition and Maximising Progress in SLA: An Integrated Method

ERIC Educational Resources Information Center

Gadd, Anna

2016-01-01

Alderson teaches us that, "progress should be the aim of all learning". With the purpose of ensuring progress and enhancing first year students' learning of Italian as a second language, research into feedback and repair was undertaken at The University of Western Australia. The research--funded by the UWA Centre for the Advancement of…

The Use of Electrochemiluminescence Assays to Predict Autoantibody and Glycemic Progression Toward Type 1 Diabetes in Individuals with Single Autoantibodies

PubMed Central

Yu, Liping; Skyler, Jay S.; Krischer, Jeffrey P.; Gottlieb, Peter A.; Boulware, David; Miao, Dongmei; Palmer, Jerry P.; Steck, Andrea K.

2017-01-01

Abstract Background: Electrochemiluminescence (ECL) assays have shown promise for enhancing the prediction of type 1 diabetes (T1D) with autoantibodies. We thus studied relatives of T1D patients to determine whether ECL assays can be used to refine risk assessments for T1D among individuals either positive for single GADA or single mIAA autoantibodies. Subjects and Methods: TrialNet Pathway to Prevention (PTP) study participants with either GADA or mIAA single autoantibodies were tested for ECL positivity during their participation in the TrialNet PTP study. Those ECL positive (ECL+) were compared with those ECL negative (ECL−) for conversion to multiple autoantibodies, 6-month glycemic progression (PS6M), and the progression to T1D. Results: The progression to multiple autoantibodies was significantly higher for those GADA/ECL+ (n = 107) than those GADA/ECL− (n = 78) (P = 0.001) and for those mIAA/ECL+ (n = 24) than those mIAA/ECL− (n = 63) (P < 0.001). The hazard ratios with 95% confidence intervals were 3.42 (1.58–7.39; P < 0.01) for GADA and 8.15 (3.02–22.00; P < 0.001) for mIAA. GADA/ECL+ and mIAA/ECL+ participants had significantly higher PS6M values than their ECL− counterparts (P = 0.001 for GADA and P = 0.009 for mIAA). Of those GADA/ECL+, 14% progressed to T1D; of those mIAA/ECL+, 17% progressed to T1D. Only 1 individual (positive for GADA) of the 141 who was ECL− progressed to T1D (median follow-up: 5 years). Conclusion: ECL measurements appear to have utility for natural history studies and prevention trials of individuals with single autoantibodies. Those ECL+ are at appreciable risk for developing multiple autoantibodies and for glycemic progression toward T1D, whereas those ECL− are at very low risk. PMID:28177779

Advanced Glycation End Products Enhance Macrophages Polarization into M1 Phenotype through Activating RAGE/NF-κB Pathway

PubMed Central

Jin, Xian; Yao, Tongqing; Zhou, Zhong'e; Zhu, Jian; Zhang, Song; Hu, Wei; Shen, Chengxing

2015-01-01

Atherosclerotic lesions are accelerated in patients with diabetes. M1 (classically activated in contrast to M2 alternatively activated) macrophages play key roles in the progression of atherosclerosis. Since advanced glycation end products (AGEs) are major pathogenic factors and active inflammation inducers in diabetes mellitus, this study assessed the effects of AGEs on macrophage polarization. The present study showed that AGEs significantly promoted macrophages to express IL-6 and TNF-α. M1 macrophage markers such as iNOS and surface markers including CD11c and CD86 were significantly upregulated while M2 macrophage markers such as Arg1 and CD206 remained unchanged after AGEs stimulation. AGEs significantly increased RAGE expression in macrophages and activated NF-κB pathway, and the aforementioned effects were partly abolished by administration of anti-RAGE antibody or NF-κB inhibitor PDTC. In conclusion, our results suggest that AGEs enhance macrophage differentiation into proinflammatory M1 phenotype at least partly via RAGE/NF-κB pathway activation. PMID:26114112

Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells.

PubMed

Pandey, Vijay; Zhang, Min; Chong, Qing-Yun; You, Mingliang; Raquib, Ainiah Rushdiana; Pandey, Amit K; Liu, Dong-Xu; Liu, Liang; Ma, Lan; Jha, Sudhakar; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E

2017-09-29

Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 ( TFF3) , in oestrogen receptor-positive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models. Clinically, elevated TFF3 protein expression was observed in EC compared with normal endometrial tissue, and its increased expression in EC was significantly associated with myometrial invasion. TAM exposure increased expression of TFF3 in ER+ EC cells and its elevated expression resulted in increased oncogenicity and invasiveness. TAM-stimulated expression of TFF3 in EC cells was associated with hypomethylation of the TFF3 promoter sequence and c-JUN/SP1-dependent transcriptional activation. In addition, small interfering ( si) RNA -mediated depletion or polyclonal antibody inhibition of TFF3 significantly abrogated oncogenicity and invasiveness in EC cells consequent to TAM induction or forced expression of TFF3. Hence, TAM-stimulated upregulation of TFF3 in EC cells was critical in promoting EC progression associated with TAM treatment. Importantly, inhibition of TFF3 function might be an attractive molecular modality to abrogate the stimulatory effects of TAM on endometrial tissue and to limit the progression of EC.

MicroRNA-101 regulates T-cell acute lymphoblastic leukemia progression and chemotherapeutic sensitivity by targeting Notch1.

PubMed

Qian, Lu; Zhang, Wanggang; Lei, Bo; He, Aili; Ye, Lianhong; Li, Xingzhou; Dong, Xin

2016-11-01

The present study aimed to investigate the role of microRNA (miR)-101 in acute lymphoblastic leukemia progression and chemoresistance. Furthermore, a novel target gene of miR-101 was identified. Here, we confirmed that miR-101 was significantly downregulated in the blood samples of patients with T-cell acute lymphoblastic leukemia (T-ALL) compared with the healthy controls, as determined by reverse transcription quantitative polymerase chain reaction (RTqPCR) analysis. The in vitro experiments demonstrated that miR-101 significantly repressed the proliferation and invasion, and induced potent apoptosis in Jurkat cells, as determined by CCK-8, flow cytometer and cell invasion assays. Luciferase assay confirmed that Notch1 was a target gene of miR-101, and western blotting showed that miR-101 suppressed the expression of Notch1 at the protein level. Moreover, functional restoration assays revealed that Notch1 mediates the effects of miR-101 on Jurkat cell proliferation, apoptosis and invasion. miR-101 enhanced the sensitivity of Jurkat cells to the chemotherapeutic agent adriamycin. Taken together, our results show for the first time that miR-101 acts as a tumor suppressor in T-cell acute lymphoblastic leukaemia and it could enhance chemotherapeutic sensitivity. Furthermore, Notch1 was identified to be a novel target of miR-101. This study indicates that miR-101 may represent a potential therapeutic target for T-cell acute lymphoblastic leukemia intervention.

Contracts for field projects and supporting research on enhanced oil recovery. Progress review number 83, quarter ending June 30, 1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Summaries of 41 research projects on enhanced recovery are presented under the following sections: (1) chemical flooding; (2) gas displacement; (3) thermal recovery; (4) geoscience technology; (5) resource assessment technology; and (6) reservoir classes. Each presentation gives the title of the project, contract number, research facility, contract date, expected completion data, amount of the award, principal investigator, and DOE program manager, and describes the objectives of the project and a summary of the technical progress.

Promoting and Scaffolding Elementary School Students' Attitudes Toward Science and Argumentation Through a Science and Society Intervention

NASA Astrophysics Data System (ADS)

Hong, Zuway-R.; Lin, Huann-shyang; Wang, Hsin-Hui; Chen, Hsiang-Ting; Yang, Kuay-Keng

2013-07-01

This study investigated the effects of a science and society intervention on elementary school students' argumentation skills and their attitudes toward science. One hundred and eleven fifth grade students volunteered as an experimental group to join a 12-week intervention; another 107 sixth grade students volunteered to be the comparison group. All participants completed the Student Questionnaire at the beginning and end of this study. Observation and interview results were used to triangulate and consolidate the quantitative findings. The data showed that after the intervention, the quality of the experimental group students' arguments and their attitudes toward science were significantly higher than their comparison group counterparts. In addition, the experimental group boys made significantly greater progress in the quality of their argumentation from the pretest to posttest than the girls; and low achievers made the most significant progress in their attitudes toward science and quality of argumentation. Interviews and observations indicated that their understandings of explanation and argumentation changed over the intervention. This indicated that a science and society intervention can enhance both the ability of students to develop strong arguments and their attitudes toward science.

Microsurgery robots: addressing the needs of high-precision surgical interventions.

PubMed

Mattos, Leonardo S; Caldwell, Darwin G; Peretti, Giorgio; Mora, Francesco; Guastini, Luca; Cingolani, Roberto

2016-01-01

Robotics has a significant potential to enhance the overall capacity and efficiency of healthcare systems. Robots can help surgeons perform better quality operations, leading to reductions in the hospitalisation time of patients and in the impact of surgery on their postoperative quality of life. In particular, robotics can have a significant impact on microsurgery, which presents stringent requirements for superhuman precision and control of the surgical tools. Microsurgery is, in fact, expected to gain importance in a growing range of surgical specialties as novel technologies progressively enable the detection, diagnosis and treatment of diseases at earlier stages. Within such scenarios, robotic microsurgery emerges as one of the key components of future surgical interventions, and will be a vital technology for addressing major surgical challenges. Nonetheless, several issues have yet to be overcome in terms of mechatronics, perception and surgeon-robot interfaces before microsurgical robots can achieve their full potential in operating rooms. Research in this direction is progressing quickly and microsurgery robot prototypes are gradually demonstrating significant clinical benefits in challenging applications such as reconstructive plastic surgery, ophthalmology, otology and laryngology. These are reassuring results offering confidence in a brighter future for high-precision surgical interventions.

EZH2-mediated repression of GSK-3β and TP53 promotes Wnt/β-catenin signaling-dependent cell expansion in cervical carcinoma.

PubMed

Chen, Qian; Zheng, Peng-Sheng; Yang, Wen-Ting

2016-06-14

Enhancer of zeste homolog 2 (EZH2), a catalytic core component of the Polycomb repressive complex 2 (PRC2), stimulates the silencing of target genes through histone H3 lysine 27 trimethylation (H3K27me3). Recent findings have indicated EZH2 is involved in the development and progression of various human cancers. However, the exact mechanism of EZH2 in the promotion of cervical cancer is largely unknown. Here, we show that EZH2 expression gradually increases during the progression of cervical cancer. We identified a significant positive correlation between EZH2 expression and cell proliferation in vitro and tumor formation in vivo by the up-regulation or down-regulation of EZH2 using CRISPR-Cas9-mediated gene editing technology and shRNA in HeLa and SiHa cells. Further investigation indicated that EZH2 protein significantly accelerated the cell cycle transition from the G0/G1 to S phase. TOP/FOP-Flash reporter assay revealed that EZH2 significantly activated Wnt/β-catenin signaling and the target genes of Wnt/β-catenin pathway were up-regulated, including β-catenin, cyclin D1, and c-myc. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed that EZH2 inhibited the expression of glycogen synthase kinase-3β (GSK-3β) and TP53 through physically interacting with motifs in the promoters of the GSK-3β and TP53 genes. Additionally, blockage of the Wnt/β-catenin pathway resulted in significant inhibition of cell proliferation, and activation of the Wnt/β-catenin pathway resulted in significant enhancement of cell proliferation, as induced by EZH2. Taken together, our data demonstrate that EZH2 promotes cell proliferation and tumor formation in cervical cancer through activating the Wnt/β-catenin pathway by epigenetic silencing via GSK-3β and TP53.

EZH2-mediated repression of GSK-3β and TP53 promotes Wnt/β-catenin signaling-dependent cell expansion in cervical carcinoma

PubMed Central

Chen, Qian; Zheng, Peng-Sheng; Yang, Wen-Ting

2016-01-01

Enhancer of zeste homolog 2 (EZH2), a catalytic core component of the Polycomb repressive complex 2 (PRC2), stimulates the silencing of target genes through histone H3 lysine 27 trimethylation (H3K27me3). Recent findings have indicated EZH2 is involved in the development and progression of various human cancers. However, the exact mechanism of EZH2 in the promotion of cervical cancer is largely unknown. Here, we show that EZH2 expression gradually increases during the progression of cervical cancer. We identified a significant positive correlation between EZH2 expression and cell proliferation in vitro and tumor formation in vivo by the up-regulation or down-regulation of EZH2 using CRISPR-Cas9-mediated gene editing technology and shRNA in HeLa and SiHa cells. Further investigation indicated that EZH2 protein significantly accelerated the cell cycle transition from the G0/G1 to S phase. TOP/FOP-Flash reporter assay revealed that EZH2 significantly activated Wnt/β-catenin signaling and the target genes of Wnt/β-catenin pathway were up-regulated, including β-catenin, cyclin D1, and c-myc. Moreover, dual-luciferase reporter and chromatin immunoprecipitation (ChIP) assays confirmed that EZH2 inhibited the expression of glycogen synthase kinase-3β (GSK-3β) and TP53 through physically interacting with motifs in the promoters of the GSK-3β and TP53 genes. Additionally, blockage of the Wnt/β-catenin pathway resulted in significant inhibition of cell proliferation, and activation of the Wnt/β-catenin pathway resulted in significant enhancement of cell proliferation, as induced by EZH2. Taken together, our data demonstrate that EZH2 promotes cell proliferation and tumor formation in cervical cancer through activating the Wnt/β-catenin pathway by epigenetic silencing via GSK-3β and TP53. PMID:27092879

Effect of treatment on titer, function, and antigen recognition of serum antibodies to Actinobacillus actinomycetemcomitans in patients with rapidly progressive periodontitis.

PubMed Central

Sjöström, K; Ou, J; Whitney, C; Johnson, B; Darveau, R; Engel, D; Page, R C

1994-01-01

Although periodontal treatment by scaling and root planing (SCRP) is known to induce bacteremia, the effect of this procedure on the host immune response is not known. We have determined pre- and post-SCRP immunoglobulin G antibody titers to antigens of Actinobacillus actinomycetemcomitans in the sera of 22 patients with rapidly progressive periodontitis. We also assessed the ability of these sera to enhance phagocytosis and killing of A. actinomycetemcomitans by human polymorphonuclear leukocytes by using a polymorphonuclear leukocyte chemiluminescence (CL) assay. Specific anti-A. actinomycetemcomitans antibody titers were significantly increased at 6 and 12 months after beginning treatment, and CL values were significantly increased at 12 months, whereas mean interproximal pocket depths were significantly decreased at 12 months after beginning treatment. When patients were classified as either seropositive (twice the median titer of control subjects; n = 10) or seronegative (n = 12), both median titers and CL values were significantly increased for the seronegative group at 6 and 12 months after treatment. In the seropositive group, only the median titer was significantly increased at 12 months. Western blot (immunoblot) patterns for six seronegative and six seropositive patients differed remarkably at the baseline. Before treatment, all of the seropositive patients recognized high-molecular-mass lipopolysaccharide (LPS) and a large number of protein components. Patterns were virtually unaffected by therapy. Before treatment, only one of the seronegative patients recognized the LPS smear and none reacted strongly with protein components. Following treatment, slight LPS staining was observed for five of six seronegative patients and detection of protein bands was enhanced in all cases. We conclude that treatment by SCRP induces a humoral immune response, especially in seronegative patients, and that response may play a role in the observed beneficial effects of periodontal treatment. Images PMID:8262620

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gabrielson, Marike; Reizer, Edwin; Stål, Olle

An increasing body of evidence is pointing towards mitochondrial regulation of the cell cycle. In a previous study of HER2-positive tumours we could demonstrate a common loss in the gene encoding for the mitochondrial transporter SLC25A43 and also a significant relation between SLC25A43 protein expression and S-phase fraction. Here, we investigated the consequence of suppressed SLC25A43 expression on cell cycle progression and proliferation in breast epithelial cells. In the present study, we suppressed SLC25A43 using siRNA in immortalised non-cancerous breast epithelial MCF10A cells and HER2-positive breast cancer cells BT-474. Viability, apoptosis, cell proliferation rate, cell cycle phase distribution, and nuclearmore » Ki-67 and p21, were assessed by flow cytometry. Cell cycle related gene expressions were analysed using real-time PCR. We found that SLC25A43 knockdown in MCF10A cells significantly inhibited cell cycle progression during G{sub 1}-to-S transition, thus significantly reducing the proliferation rate and fraction of Ki-67 positive MCF10A cells. In contrast, suppressed SLC25A43 expression in BT-474 cells resulted in a significantly increased proliferation rate together with an enhanced G{sub 1}-to-S transition. This was reflected by an increased fraction of Ki-67 positive cells and reduced level of nuclear p21. In line with our previous results, we show a role for SLC25A43 as a regulator of cell cycle progression and proliferation through a putative mitochondrial checkpoint. These novel data further strengthen the connection between mitochondrial function and the cell cycle, both in non-malignant and in cancer cells. - Highlights: • Proposed cell cycle regulation through the mitochondrial transporter SLC25A43. • SLC25A43 alters cell proliferation rate and cell cycle progression. • Suppressed SLC25A43 influences transcription of cell cycle regulatory genes.« less

Experience-Dependent Effects of Cocaine Self-Administration/Conditioning on Prefrontal and Accumbens Dopamine Responses

PubMed Central

Ikegami, Aiko; Olsen, Christopher M.; D’Souza, Manoranjan S.; Duvauchelle, Christine L.

2008-01-01

Experiments were performed to examine the effects of cocaine self-administration and conditioning experience on operant behavior, locomotor activity, and nucleus accumbens (NAcc) and prefrontal cortex (PFC) dopamine (DA) responses. Sensory cues were paired with alternating cocaine and nonreinforcement during 12 (limited training) or 40 (long-term training) daily operant sessions. After limited training, NAcc DA responses to cocaine were significantly enhanced in the presence of cocaine-associated cues compared with nonreward cues and significantly depressed after cocaine-paired cues accompanied a nonreinforced lever response. PFC DA levels were generally nonresponsive to cues after the same training duration. However, after long-term training, cocaine-associated cues increased the magnitude of cocaine-stimulated PFC DA levels significantly over levels observed with nonreinforcement cues. Conversely, conditioned cues no longer influenced NAcc DA levels after long-term training. In addition, cocaine-stimulated locomotor activity was enhanced by cocaine-paired cues after long-term, but not after limited, training. Findings demonstrate that cue-induced cocaine expectation exerts a significant impact on dopaminergic and behavioral systems, progressing from mesolimbic to mesocortical regions and from latent to patent behaviors as cocaine and associative experiences escalate. PMID:17469929

Does hypervascularity of liver metastases as detected on MRI predict disease progression in breast cancer patients?

PubMed

Braga, Larissa; Semelka, Richard C; Pietrobon, Ricardo; Martin, Diego; de Barros, Nestor; Guller, Ulrich

2004-05-01

The aim of our study was to evaluate the association of the vascularity of liver metastases, as characterized by MRI, and disease progression in breast cancer patients. Sixteen breast cancer patients with liver metastases who underwent MRI before and after systemic therapy were retrospectively identified. On the basis of comparison of each MRI examination with the previous examination, disease status of the patients was classified as complete response, partial response, stable disease, or progressive disease. Liver metastases were characterized as hyper- or hypovascular on the basis of the degree of enhancement in the arterial, portal, and interstitial phases of imaging after administration of a contrast agent. Fisher's exact test and ordinal logistic regression models, including the type of systemic therapy, presence of multiple metastases, and hormone receptor status, were used to estimate the unadjusted and risk-adjusted association between the presence of hypervascular liver metastases and disease progression. All patients in our sample (n = 16) were women and most (12/16, 75%) were white. Their median age was 51.5 years. In unadjusted analyses, the association between the presence of hypervascular liver metastases and disease progression was statistically significant (p < 0.0001). In multiple logistic regression analyses, hypervascular liver metastases were found to be an independent predictor of disease progression. Patients with hypervascular liver lesions were 20.5 times more likely to experience disease progression than patients without hypervascular metastases (odds ratio, 20.5; 95% confidence interval, 5.1-83.5; p < 0.0001). Our analysis provides suggestive evidence that disease progression can be predicted through MRI assessment of the vascularity of liver metastases in patients with breast cancer.

Pleiotropic biological activities of alternatively spliced TMPRSS2/ERG fusion gene transcripts

PubMed Central

Wang, Jianghua; Cai, Yi; Yu, Wendong; Ren, Chengxi; Spencer, David M.; Ittmann, Michael

2008-01-01

TMPRSS2/ERG gene fusions are found in the majority of prostate cancers; however, there is significant heterogeneity in the 5′ region of the alternatively spliced fusion gene transcripts. We have found that there is also significant heterogeneity within the coding exons as well. There is variable inclusion of a 72-bp exon and other novel alternatively spliced isoforms. To assess the biological significance of these alternatively spliced transcripts, we expressed various transcripts in primary prostatic epithelial cells and in an immortalized prostatic epithelial cell line, PNT1a. The fusion gene transcripts promoted proliferation, invasion and motility with variable activities that depended on the structure of the 5′ region encoding the TMPRSS2/ERG fusion and the presence of the 72-bp exon. Cotransfection of different isoforms further enhanced biological activity, mimicking the situation in vivo, in which multiple isoforms are expressed. Finally, knockdown of the fusion gene in VCaP cells resulted in inhibition of proliferation in vitro and tumor progression in an in vivo orthotopic mice model. Our results indicate that TMPRSS2/ERG fusion isoforms have variable biological activities promoting tumor initiation and progression and are consistent with our previous clinical observations indicating that certain TMPRSS2/ERG fusion isoforms are significantly correlated with more aggressive disease. PMID:18922926

IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.

PubMed

Bie, Qingli; Zhang, Bin; Sun, Caixia; Ji, Xiaoyun; Barnie, Prince Amoah; Qi, Chen; Peng, Jingjing; Zhang, Danyi; Zheng, Dong; Su, Zhaoliang; Wang, Shengjun; Xu, Huaxi

2017-03-21

Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

Transgenic expression of human neutrophil peptide-1 enhances hepatic fibrosis in mice fed a choline-deficient, L-amino acid-defined diet.

PubMed

Ibusuki, Rie; Uto, Hirofumi; Arima, Shiho; Mawatari, Seiichi; Setoguchi, Yoshiko; Iwashita, Yuji; Hashimoto, Shinichi; Maeda, Takuro; Tanoue, Shiro; Kanmura, Shuji; Oketani, Makoto; Ido, Akio; Tsubouchi, Hirohito

2013-11-01

Neutrophils infiltrate the livers of patients with nonalcoholic steatohepatitis (NASH). Human neutrophil peptides (HNPs) induce cytokine and chemokine production under inflammatory conditions, which may contribute to the progression of NASH. In this study, we focused on the effects of HNP-1 on hepatic steatosis and fibrosis in a mouse model of NASH induced by a choline-deficient, L-amino acid-defined (CDAA) diet. We generated transgenic mice expressing HNP-1 under the control of a β-actin-based promoter. HNP-1 transgenic and wild-type C57BL/6N mice were fed a CDAA diet for 16 weeks to induce hepatic steatosis and fibrosis. Serological and histological features were examined, and the effects of HNP-1 on hepatic stellate cell lines were assessed. HNP-1 transgenic and wild-type mice fed the CDAA diet showed no significant differences in serum alanine aminotransferase levels or the degree of hepatic steatosis based on Oil red O staining and hepatic triglyceride content. In contrast, Sirius Red and Azan staining showed significantly more severe hepatic fibrosis in HNP-1 transgenic mice compared with wild-type mice. In addition, significantly more α-smooth muscle actin-positive hepatic stellate cells were observed in the transgenic mice than in the wild-type mice. Finally, the proliferation of the LI90 hepatic stellate cell line increased in response to HNP-1. Our data indicate that HNP-1 enhances hepatic fibrosis in fatty liver by inducing hepatic stellate cell proliferation. Thus, neutrophil-derived HNP-1 may contribute to the progression of NASH. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab

PubMed Central

Lassau, N.; Coiffier, B.; Kind, M.; Vilgrain, V.; Lacroix, J.; Cuinet, M.; Taieb, S.; Aziza, R.; Sarran, A.; Labbe-Devilliers, C.; Gallix, B.; Lucidarme, O.; Ptak, Y.; Rocher, L.; Caquot, L. M.; Chagnon, S.; Marion, D.; Luciani, A.; Feutray, S.; Uzan-Augui, J.; Benatsou, B.; Bonastre, J.; Koscielny, S.

2016-01-01

Background Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients and methods Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. Results The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. Conclusion The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. AFSSAPS No 2007-A00399-44. PMID:27502701

Transforming growth factor-beta regulates mammary carcinoma cell survival and interaction with the adjacent microenvironment.

PubMed

Bierie, Brian; Stover, Daniel G; Abel, Ty W; Chytil, Anna; Gorska, Agnieszka E; Aakre, Mary; Forrester, Elizabeth; Yang, Li; Wagner, Kay-Uwe; Moses, Harold L

2008-03-15

Transforming growth factor (TGF)-beta signaling has been associated with early tumor suppression and late tumor progression; however, many of the mechanisms that mediate these processes are not known. Using Cre/LoxP technology, with the whey acidic protein promoter driving transgenic expression of Cre recombinase (WAP-Cre), we have now ablated the type II TGF-beta receptor (T beta RII) expression specifically within mouse mammary alveolar progenitors. Transgenic expression of the polyoma virus middle T antigen, under control of the mouse mammary tumor virus enhancer/promoter, was used to produce mammary tumors in the absence or presence of Cre (T beta RII((fl/fl);PY) and T beta RII((fl/fl);PY;WC), respectively). The loss of TGF-beta signaling significantly decreased tumor latency and increased the rate of pulmonary metastasis. The loss of TGF-beta signaling was significantly correlated with increased tumor size and enhanced carcinoma cell survival. In addition, we observed significant differences in stromal fibrovascular abundance and composition accompanied by increased recruitment of F4/80(+) cell populations in T beta RII((fl/fl);PY;WC) mice when compared with T beta RII((fl/fl);PY) controls. The recruitment of F4/80(+) cells correlated with increased expression of known inflammatory genes including Cxcl1, Cxcl5, and Ptgs2 (cyclooxygenase-2). Notably, we also identified an enriched K5(+) dNp63(+) cell population in primary T beta RII((fl/fl);PY;WC) tumors and corresponding pulmonary metastases, suggesting that loss of TGF-beta signaling in this subset of carcinoma cells can contribute to metastasis. Together, our current results indicate that loss of TGF-beta signaling in mammary alveolar progenitors may affect tumor initiation, progression, and metastasis through regulation of both intrinsic cell signaling and adjacent stromal-epithelial interactions in vivo.

Making Progress: The Use of Multiple Progress Reports to Enhance Advertising Students' Media Plan Term Projects

ERIC Educational Resources Information Center

Kritz, Gary H.; Lozada, Hector R.; Long, Mary M.

2007-01-01

Since the AACSB mandates that students demonstrate effective oral and written communication skills, it is imperative that business professors do what is necessary to improve such skills. The authors investigate whether the use of using multiple progress reports in an Advertising class project improves the final product. The data results show that…

Advances in adult acute lymphoblastic leukemia therapy.

PubMed

Aldoss, Ibrahim; Stein, Anthony S

2018-05-01

Progress in adult acute lymphoblastic leukemia (ALL) treatment has been met with challenge until recently. A steady improvement in outcomes is being witnessed among adults with ALL, and it will be enhanced further with early referral of newly diagnosed ALL patients to specialized centers, enrolling more ALL adults in clinical trials, adopting pediatric-inspired ALL regimens in younger adults, tailoring treatments according to minimal residual disease response and disease genetics, incorporating novel therapies and tyrosine kinase inhibitors in frontline regimens, early referral to transplant when indicated, expanding the donor pool, and developing more effective salvage therapies for relapsed/refractory ALL. In this review, we will discuss the most significant advances in treating adult ALL observed in the last five years that have the potential to enhance adult ALL treatment and outcome.

Polycrystalline Diamond Coating of Additively Manufactured Titanium for Biomedical Applications.

PubMed

Rifai, Aaqil; Tran, Nhiem; Lau, Desmond W; Elbourne, Aaron; Zhan, Hualin; Stacey, Alastair D; Mayes, Edwin L H; Sarker, Avik; Ivanova, Elena P; Crawford, Russell J; Tran, Phong A; Gibson, Brant C; Greentree, Andrew D; Pirogova, Elena; Fox, Kate

2018-03-14

Additive manufacturing using selective laser melted titanium (SLM-Ti) is used to create bespoke items across many diverse fields such as medicine, defense, and aerospace. Despite great progress in orthopedic implant applications, such as for "just in time" implants, significant challenges remain with regards to material osseointegration and the susceptibility to bacterial colonization on the implant. Here, we show that polycrystalline diamond coatings on these titanium samples can enhance biological scaffold interaction improving medical implant applicability. The highly conformable coating exhibited excellent bonding to the substrate. Relative to uncoated SLM-Ti, the diamond coated samples showed enhanced mammalian cell growth, enriched apatite deposition, and reduced microbial S. aureus activity. These results open new opportunities for novel coatings on SLM-Ti devices in general and especially show promise for improved biomedical implants.

Tumor Progression Is Mediated by Thymosin-β4 through a TGFβ/MRTF Signaling Axis.

PubMed

Morita, Tsuyoshi; Hayashi, Ken'ichiro

2018-05-01

Although enhanced thymosin β4 (TMSB4X/Tβ4) expression is associated with tumor progression and metastasis, its tumor-promoting functions remain largely unknown. Here, it is demonstrated that TGFβ facilitates Tβ4 expression and leads to the activation of myocardin-related transcription factors (MRTF), which are coactivators of serum response factor (SRF) and regulate the expression of genes critical for the epithelial-mesenchymal transition (EMT) and tumor metastasis. In murine mammary gland cells (NMuMG), Tβ4 upregulation is required for full induction of a MRTF-regulated EMT gene expression program after TGFβ stimulation. Tβ4 levels are transcriptionally regulated via the novel cis -acting element AGACAAAG, which interacts with Smad and T-cell factor/lymphoid enhancer factor (TCF/LEF) to synergistically activate the Tβ4 promoter downstream of TGFβ. Murine skin melanoma cells (B16F0 and B16F1) also show the expression regulation of Tβ4 by Smad and TCF/LEF. Tβ4-knockout B16F1 (Tβ4 KO) clones show significantly diminished expression level of tumor-associated genes, which is regulated by the TGFβ/MRTFs pathway. In multiple human cancers, Tβ4 levels correlate positively with TGFβ1 and the tumor-associated gene expression levels through processes that respectively depend on TGFβ receptor 1 (TGFBR1) and MRTF expression. Kaplan-Meier survival analyses demonstrate that high Tβ4 expression associates with poor prognosis in an SRF expression-dependent manner in several cancers. In mice, Tβ4 KO clones show significantly decreased experimental metastatic potential; furthermore, ectopic expression of constitutively active MRTF-A fully restores the diminished metastatic activity. In conclusion, the TGFβ/Tβ4/MRTF/SRF pathway is critical for metastasis and tumor progression. Implications: These findings define a molecular mechanism underlying a tumor-promoting function of thymosin β4 through activation of MRTF/SRF signaling. Mol Cancer Res; 16(5); 880-93. ©2018 AACR . ©2018 American Association for Cancer Research.

Liposomal temozolomide drug delivery using convection enhanced delivery.

PubMed

Nordling-David, Mirjam M; Yaffe, Roni; Guez, David; Meirow, Hadar; Last, David; Grad, Etty; Salomon, Sharona; Sharabi, Shirley; Levi-Kalisman, Yael; Golomb, Gershon; Mardor, Yael

2017-09-10

Even though some progress in diagnosis and treatment has been made over the years, there is still no definitive treatment available for Glioblastoma multiforme (GBM). Convection-enhanced delivery (CED), a continuous infusion-mediated pressure gradient via intracranial catheters, studied in clinical trials, enables in situ drug concentrations several orders of magnitude greater than those achieved by systemic administration. We hypothesized that the currently limited efficacy of CED could be enhanced by a liposomal formulation, thus achieving enhanced drug localization to the tumor site with minimal toxicity. We hereby describe a novel approach for treating GBM by CED of liposomes containing the known chemotherapeutic agent, temozolomide (TMZ). A new technique for encapsulating TMZ in hydrophilic (PEGylated) liposomes, characterized by nano-size (121nm), low polydispersity index (<0.13) and with near-neutral charge (-ʒ,0.2mV), has been developed. Co-infusion of PEGylated Gd-DTPA liposomes and TMZ-liposomes by CED in GBM bearing rats, resulted in enhanced tumor detection with longer residence time than free Gd-DTPA. Treatment of GBM-bearing rats with either TMZ solution or TMZ-liposomes resulted in greater tumor inhibition and significantly higher survival. However, the longer survival and smaller tumor volumes exhibited by TMZ liposomal treatment in comparison to TMZ in solution were insignificant (p<0.053); and only significantly lower edema volumes were observed. Thus, there are no clear-cut advantages to use a liposomal delivery system of TMZ via CED over a drug solution. Copyright © 2017 Elsevier B.V. All rights reserved.

Portable wireless neurofeedback system of EEG alpha rhythm enhances memory.

PubMed

Wei, Ting-Ying; Chang, Da-Wei; Liu, You-De; Liu, Chen-Wei; Young, Chung-Ping; Liang, Sheng-Fu; Shaw, Fu-Zen

2017-11-13

Effect of neurofeedback training (NFT) on enhancement of cognitive function or amelioration of clinical symptoms is inconclusive. The trainability of brain rhythm using a neurofeedback system is uncertainty because various experimental designs are used in previous studies. The current study aimed to develop a portable wireless NFT system for alpha rhythm and to validate effect of the NFT system on memory with a sham-controlled group. The proposed system contained an EEG signal analysis device and a smartphone with wireless Bluetooth low-energy technology. Instantaneous 1-s EEG power and contiguous 5-min EEG power throughout the training were developed as feedback information. The training performance and its progression were kept to boost usability of our device. Participants were blinded and randomly assigned into either the control group receiving random 4-Hz power or Alpha group receiving 8-12-Hz power. Working memory and episodic memory were assessed by the backward digital span task and word-pair task, respectively. The portable neurofeedback system had advantages of a tiny size and long-term recording and demonstrated trainability of alpha rhythm in terms of significant increase of power and duration of 8-12 Hz. Moreover, accuracies of the backward digital span task and word-pair task showed significant enhancement in the Alpha group after training compared to the control group. Our tiny portable device demonstrated success trainability of alpha rhythm and enhanced two kinds of memories. The present study suggest that the portable neurofeedback system provides an alternative intervention for memory enhancement.

USP22 regulates oncogenic signaling pathways to drive lethal cancer progression.

PubMed

Schrecengost, Randy S; Dean, Jeffry L; Goodwin, Jonathan F; Schiewer, Matthew J; Urban, Mark W; Stanek, Timothy J; Sussman, Robyn T; Hicks, Jessica L; Birbe, Ruth C; Draganova-Tacheva, Rossitza A; Visakorpi, Tapio; DeMarzo, Angelo M; McMahon, Steven B; Knudsen, Karen E

2014-01-01

Increasing evidence links deregulation of the ubiquitin-specific proteases 22 (USP22) deubitiquitylase to cancer development and progression in a select group of tumor types, but its specificity and underlying mechanisms of action are not well defined. Here we show that USP22 is a critical promoter of lethal tumor phenotypes that acts by modulating nuclear receptor and oncogenic signaling. In multiple xenograft models of human cancer, modeling of tumor-associated USP22 deregulation demonstrated that USP22 controls androgen receptor accumulation and signaling, and that it enhances expression of critical target genes coregulated by androgen receptor and MYC. USP22 not only reprogrammed androgen receptor function, but was sufficient to induce the transition to therapeutic resistance. Notably, in vivo depletion experiments revealed that USP22 is critical to maintain phenotypes associated with end-stage disease. This was a significant finding given clinical evidence that USP22 is highly deregulated in tumors, which have achieved therapeutic resistance. Taken together, our findings define USP22 as a critical effector of tumor progression, which drives lethal phenotypes, rationalizing this enzyme as an appealing therapeutic target to treat advanced disease.

GABA(A) and dopamine receptors in the nucleus accumbens shell differentially influence performance of a water-reinforced progressive ratio task.

PubMed

Covelo, Ignacio R; Wirtshafter, David; Stratford, Thomas R

2012-03-01

Several authors have shown that injections of the GABA(A) agonist muscimol into the medial shell region of the nucleus accumbens (AcbSh) result in large increases in food, but not water, intake. In previous studies we demonstrated that intra-AcbSh injections of either muscimol or of the indirect dopamine agonist amphetamine increase response output on a food-reinforced progressive ratio schedule. In the current experiment we extended these observations by examining the effects of muscimol and amphetamine injections on the performance of a water-reinforced progressive ratio task in mildly deprived animals. We found that muscimol did not affect the number of responses made in the water-reinforced task, even though a marked increase in responding was observed after amphetamine. Muscimol did, however, significantly increase food intake in the same animals. The results suggest that the enhancing effects of intra-AcbSh muscimol differ from those of amphetamine in that they are selective for food-reinforced behaviors. Copyright © 2011. Published by Elsevier Inc.

Chemicals to enhance microalgal growth and accumulation of high-value bioproducts

PubMed Central

Yu, Xinheng; Chen, Lei; Zhang, Weiwen

2015-01-01

Photosynthetic microalgae have attracted significant attention as they can serve as important sources for cosmetic, food and pharmaceutical products, industrial materials and even biofuel biodiesels. However, current productivity of microalga-based processes is still very low, which has restricted their scale-up application. In addition to various efforts in strain improvement and cultivation optimization, it was proposed that the productivity of microalga-based processes can also be increased using various chemicals to trigger or enhance cell growth and accumulation of bioproducts. Herein, we summarized recent progresses in applying chemical triggers or enhancers to improve cell growth and accumulation of bioproducts in algal cultures. Based on their enhancing mechanisms, these chemicals can be classified into four categories:chemicals regulating biosynthetic pathways, chemicals inducing oxidative stress responses, phytohormones and analogs regulating multiple aspects of microalgal metabolism, and chemicals directly as metabolic precursors. Taken together, the early researches demonstrated that the use of chemical stimulants could be a very effective and economical way to improve cell growth and accumulation of high-value bioproducts in large-scale cultivation of microalgae. PMID:25741321

78 FR 75383 - Duke Energy Progress; Shearon Harris Units 2 and 3; Exemption From Requirements To Revise...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... Address Enhancements to Emergency Preparedness Rules AGENCY: Nuclear Regulatory Commission. ACTION... their COL application in order to address enhancements to the Emergency Preparedness (EP) rules within... Safety The underlying purpose of the enhancements to Emergency Preparedness found in 10 CFR part 50...

Reliability of Semi-Automated Segmentations in Glioblastoma.

PubMed

Huber, T; Alber, G; Bette, S; Boeckh-Behrens, T; Gempt, J; Ringel, F; Alberts, E; Zimmer, C; Bauer, J S

2017-06-01

In glioblastoma, quantitative volumetric measurements of contrast-enhancing or fluid-attenuated inversion recovery (FLAIR) hyperintense tumor compartments are needed for an objective assessment of therapy response. The aim of this study was to evaluate the reliability of a semi-automated, region-growing segmentation tool for determining tumor volume in patients with glioblastoma among different users of the software. A total of 320 segmentations of tumor-associated FLAIR changes and contrast-enhancing tumor tissue were performed by different raters (neuroradiologists, medical students, and volunteers). All patients underwent high-resolution magnetic resonance imaging including a 3D-FLAIR and a 3D-MPRage sequence. Segmentations were done using a semi-automated, region-growing segmentation tool. Intra- and inter-rater-reliability were addressed by intra-class-correlation (ICC). Root-mean-square error (RMSE) was used to determine the precision error. Dice score was calculated to measure the overlap between segmentations. Semi-automated segmentation showed a high ICC (> 0.985) for all groups indicating an excellent intra- and inter-rater-reliability. Significant smaller precision errors and higher Dice scores were observed for FLAIR segmentations compared with segmentations of contrast-enhancement. Single rater segmentations showed the lowest RMSE for FLAIR of 3.3 % (MPRage: 8.2 %). Both, single raters and neuroradiologists had the lowest precision error for longitudinal evaluation of FLAIR changes. Semi-automated volumetry of glioblastoma was reliably performed by all groups of raters, even without neuroradiologic expertise. Interestingly, segmentations of tumor-associated FLAIR changes were more reliable than segmentations of contrast enhancement. In longitudinal evaluations, an experienced rater can detect progressive FLAIR changes of less than 15 % reliably in a quantitative way which could help to detect progressive disease earlier.

Advanced teaching labs in physics - celebrating progress; challenges ahead

NASA Astrophysics Data System (ADS)

Peterson, Richard

A few examples of optical physics experiments may help us first reflect on significant progress on how advanced lab initiatives may now be more effectively developed, discussed, and disseminated - as opposed to only 10 or 15 years back. Many cooperative developments of the last decade are having profound impacts on advanced lab workers and students. Central to these changes are the programs of the Advanced Laboratory Physics Association (ALPhA) (Immersions, BFY conferences), AAPT (advlab-l server, ComPADRE, apparatus competitions, summer workshops/sessions), APS (Reichert Award, FEd activities and sessions), and the Jonathan F. Reichert Foundation (ALPhA support and institution matched equipment grants for Immersion participants). Broad NSF support has helped undergird several of these initiatives. Two of the most significant challenges before this new advanced lab community are (a) to somehow enhance funding opportunities for teaching equipment and apparatus in an era of minimal NSF equipment support, and (b) to help develop a more complementary relationship between research-based advanced lab pedagogies and the development of fresh physics experiments that help enable the mentoring and experimental challenge of our students.

Effect of C content on the mechanical properties of solution treated as-cast ASTM F-75 alloys.

PubMed

Herrera, M; Espinoza, A; Méndez, J; Castro, M; López, J; Rendón, J

2005-07-01

The mechanical properties of solution treated ASTM F-75 alloys with various carbon contents have been studied. Alloys cast under the same conditions were subjected to solution treatment for several periods and then their tensile properties were evaluated. In the as-cast conditions, the alloys exhibited higher strength values with increasing carbon content whereas their ductility was not significantly affected. For the solution treated alloys, the variation of the strength was characterized by a progressive increase for short treatment times until a maximum value was achieved, which was followed by a diminution in this property for longer treatment times. This behavior was more accentuated for the case of the alloys with medium carbon contents, which also exhibited the highest values of strength. Furthermore, the alloy's ductility was enhanced progressively with increasing solution treatment time. This improvement in ductility was significantly higher for the medium carbon alloys compared with the rest of the studied alloys. Thus, high and low carbon contents in solution treated ASTM F-75 alloys did not produced sufficiently high tensile properties.

Podoplanin increases migration and angiogenesis in malignant glioma

PubMed Central

Grau, Stefan J; Trillsch, Fabian; Tonn, Joerg-Christian; Goldbrunner, Roland H; Noessner, Elfriede; Nelson, Peter J; von Luettichau, Irene

2015-01-01

Expression of podoplanin in glial brain tumors is grade dependent. While serving as a marker for tumor progression and modulating invasion in various neoplasms, little is known about podoplanin function in gliomas. Therefore we stably transfected two human glioma cell lines (U373MG and U87MG) with expression plasmids encoding podoplanin. The efficacy of transfection was confirmed by FACS analysis, PCR and immunocytochemistry. Cells were then sorted for highly podoplanin expressing cells (U373Phigh/U87Phigh). Transfection did not influence the production of pro-angiogenic factors including VEGF, VEGF-C and D. Also, expression of VEGF receptors (VEGFR) remained unchanged except for U87Phigh, where a VEGFR3 expression was induced. U373Phigh showed significantly reduced proliferation as compared to mock transfected group. By contrast, podoplanin significantly increased migration and invasion into collagen matrix. Furthermore, conditioned media from Phigh glioma cells strongly induced tube formation on matrigel. In conclusion, podoplanin increased migration of tumor cells and enhanced tube formation activity in endothelial cells independent from VEGF. Thus, podoplanin expression may be an important step in tumor progression. PMID:26339454

Targeting Hypoxia-Inducible Factor-1α/Pyruvate Dehydrogenase Kinase 1 Axis by Dichloroacetate Suppresses Bleomycin-induced Pulmonary Fibrosis.

PubMed

Goodwin, Justin; Choi, Hyunsung; Hsieh, Meng-Hsiung; Neugent, Michael L; Ahn, Jung-Mo; Hayenga, Heather N; Singh, Pankaj K; Shackelford, David B; Lee, In-Kyu; Shulaev, Vladimir; Dhar, Shanta; Takeda, Norihiko; Kim, Jung-Whan

2018-02-01

Hypoxia has long been implicated in the pathogenesis of fibrotic diseases. Aberrantly activated myofibroblasts are the primary pathological driver of fibrotic progression, yet how various microenvironmental influences, such as hypoxia, contribute to their sustained activation and differentiation is poorly understood. As a defining feature of hypoxia is its impact on cellular metabolism, we sought to investigate how hypoxia-induced metabolic reprogramming affects myofibroblast differentiation and fibrotic progression, and to test the preclinical efficacy of targeting glycolytic metabolism for the treatment of pulmonary fibrosis. Bleomycin-induced pulmonary fibrotic progression was evaluated in two independent, fibroblast-specific, promoter-driven, hypoxia-inducible factor (Hif) 1A knockout mouse models and in glycolytic inhibitor, dichloroacetate-treated mice. Genetic and pharmacological approaches were used to explicate the role of metabolic reprogramming in myofibroblast differentiation. Hypoxia significantly enhanced transforming growth factor-β-induced myofibroblast differentiation through HIF-1α, whereas overexpression of the critical HIF-1α-mediated glycolytic switch, pyruvate dehydrogenase kinase 1 (PDK1) was sufficient to activate glycolysis and potentiate myofibroblast differentiation, even in the absence of HIF-1α. Inhibition of the HIF-1α/PDK1 axis by genomic deletion of Hif1A or pharmacological inhibition of PDK1 significantly attenuated bleomycin-induced pulmonary fibrosis. Our findings suggest that HIF-1α/PDK1-mediated glycolytic reprogramming is a critical metabolic alteration that acts to promote myofibroblast differentiation and fibrotic progression, and demonstrate that targeting glycolytic metabolism may prove to be a potential therapeutic strategy for the treatment of pulmonary fibrosis.

Analysis of simian virus 40 small t antigen-induced progression of rat F111 cells minimally transformed by large T antigen.

PubMed Central

Zerrahn, J; Deppert, W

1993-01-01

Minimal transformants of rat F111 fibroblasts were established after infection with the large T antigen (large T)-encoding retroviral expression vector pZIPTEX (M. Brown, M. McCormack, K. Zinn, M. Farrell, I. Bikel, and D. Livingston, J. Virol. 60:290-293, 1986). Coexpression of small t antigen (small t) in these cells efficiently led to their progression toward a significantly enhanced transformed phenotype. Small t forms a complex with phosphatase 2A and thereby might influence cellular phosphorylation processes, including the phosphorylation of large T. Since phosphorylation can modulate the transforming activity of large T, we asked whether the phosphorylation status of large T in minimally transformed cells might differ from that of large T in maximally transformed FR(wt648) cells and whether it might be altered by coexpression of small t. We found the phosphate turnover on large T in minimally transformed cells significantly different from that in fully transformed cells. This resulted in underphosphorylation of large T in minimally transformed cells at phosphorylation sites previously shown to be involved in the regulation of the transforming activity of large T. However, coexpression of small t in the minimally transformed cells did not alter the phosphate turnover on large T during progression; i.e., it did not induce a change in the steady-state phosphorylation of large T. This suggests that the helper function of small t during the progression of these cells was not mediated by modulating phosphatase 2A activity toward large T. Images PMID:8382310

Imaging outcome measures for progressive multiple sclerosis trials

PubMed Central

Moccia, Marcello; de Stefano, Nicola; Barkhof, Frederik

2017-01-01

Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Position emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation. PMID:29041865

‘Serpent in the spine’: a case of giant spinal ependymoma of cervicothoracic spine

PubMed Central

Arrifin, Arlizan; Kaliaperumal, Chandrasekaran; Keohane, Catherine; O'Sullivan, Michael

2012-01-01

We describe a case of giant spinal ependymoma of cervicothoracic spine in a 30-year-old lady who presented with progressive spastic paraparesis and significant combined upper and lower motor neuron signs in her lower limbs over a 1-year period. She also had upper limb small muscle wasting with absent reflexes and diminished sensation. She was wheel chair bound with involvement of sphincters. Neuroimaging revealed a uniformly enhancing intramedullary lesion from C2–T3 level with associated syringomyelia. She underwent a complete excision of this World Health Organisation (WHO) II cellular ependymoma, resulting in significant clinical outcome and improvement in bladder and bowel function. PMID:22739334

Aircraft fire safety research

NASA Technical Reports Server (NTRS)

Botteri, Benito P.

1987-01-01

During the past 15 years, very significant progress has been made toward enhancing aircraft fire safety in both normal and hostile (combat) operational environments. Most of the major aspects of the aircraft fire safety problem are touched upon here. The technology of aircraft fire protection, although not directly applicable in all cases to spacecraft fire scenarios, nevertheless does provide a solid foundation to build upon. This is particularly true of the extensive research and testing pertaining to aircraft interior fire safety and to onboard inert gas generation systems, both of which are still active areas of investigation.

Photonics for microwave systems and ultra-wideband signal processing

NASA Astrophysics Data System (ADS)

Ng, W.

2016-08-01

The advantages of using the broadband and low-loss distribution attributes of photonics to enhance the signal processing and sensing capabilities of microwave systems are well known. In this paper, we review the progress made in the topical areas of true-time-delay beamsteering, photonic-assisted analog-to-digital conversion, RF-photonic filtering and link performances. We also provide an outlook on the emerging field of integrated microwave photonics (MWP) that promise to reduce the cost of MWP subsystems and components, while providing significantly improved form-factors for system insertion.

[Acute mesenteric ischemia: do biomarkers contribute to diagnosis?].

PubMed

Rosero, Olivér; Harsányi, László; Szijártó, Attila

2014-10-12

Acute mesenteric ischemia is an emergency condition that requires immediate therapy. Despite advances in the fields of surgery and intensive therapy, the mortality of this condition remains high. This is due to the broad variability of clinical presentations and non-specific laboratory findings, which delay the diagnosis allowing the ischemia to progress and further worsening the patients' chances of survival. Thus, there is a significant need for reliable and enhanced serological markers of intestinal ischemia. The authors review the traditionally used and novel experimental serological markers for early diagnosis of mesenteric ischemia.

Intelligence moderates reinforcement learning: a mini-review of the neural evidence

PubMed Central

2014-01-01

Our understanding of the neural basis of reinforcement learning and intelligence, two key factors contributing to human strivings, has progressed significantly recently. However, the overlap of these two lines of research, namely, how intelligence affects neural responses during reinforcement learning, remains uninvestigated. A mini-review of three existing studies suggests that higher IQ (especially fluid IQ) may enhance the neural signal of positive prediction error in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum, several brain substrates of reinforcement learning or intelligence. PMID:25185818

Intelligence moderates reinforcement learning: a mini-review of the neural evidence.

PubMed

Chen, Chong

2015-06-01

Our understanding of the neural basis of reinforcement learning and intelligence, two key factors contributing to human strivings, has progressed significantly recently. However, the overlap of these two lines of research, namely, how intelligence affects neural responses during reinforcement learning, remains uninvestigated. A mini-review of three existing studies suggests that higher IQ (especially fluid IQ) may enhance the neural signal of positive prediction error in dorsolateral prefrontal cortex, dorsal anterior cingulate cortex, and striatum, several brain substrates of reinforcement learning or intelligence. Copyright © 2015 the American Physiological Society.

Necrotizing pancreatitis: challenges and solutions.

PubMed

Bendersky, Victoria A; Mallipeddi, Mohan K; Perez, Alexander; Pappas, Theodore N

2016-01-01

Acute pancreatitis is a common disease that can progress to gland necrosis, which imposes significant risk of morbidity and mortality. In general, the treatment for pancreatitis is a supportive therapy. However, there are several reasons to escalate to surgery or another intervention. This review discusses the pathophysiology as well as medical and interventional management of necrotizing pancreatitis. Current evidence suggests that patients are best served by delaying interventions for at least 4 weeks, draining as a first resort, and debriding recalcitrant tissue using minimally invasive techniques to promote or enhance postoperative recovery while reducing wound-related complications.

Progress of Rugby Hohlraum Experiments on Omega

NASA Astrophysics Data System (ADS)

Philippe, Franck; Tassin, Veronique; Casner, Alexis; Gauthier, Pascal; Seytor, Patricia; Monteil, Marie-Christine; Park, Hye-Sook; Robey, Harry; Ross, Steven; Amendt, Peter; Girard, Frederic; Villette, Bruno; Reverdin, Charles; Loiseau, Pascal; Caillaud, Tony; Landoas, Olivier; Li, Chi Kang; Petrasso, Richard; Seguin, Fredrick; Rosenberg, Markus

2011-10-01

The rugby hohlraum concept is predicted to enable better coupling and higher gains in the indirect drive approach to ignition. A collaborative experimental program is currently pursued on OMEGA to test this concept in preparation for future megajoule-scale ignition designs. A direct comparison of gas-filled rugby hohlraums with classical cylinders was recently performed, showing a significant (up to ~40%) observed x-ray drive enhancement and neutron yields that are consistently higher in the rugby case. This work extends and confirms our previous findings in empty rugby hohlraums.

Wall enhancement on high-resolution magnetic resonance imaging may predict an unsteady state of an intracranial saccular aneurysm.

PubMed

Hu, Peng; Yang, Qi; Wang, Dan-Dan; Guan, Shao-Chen; Zhang, Hong-Qi

2016-10-01

The aneurysm wall has been reported to play a critical role in the formation, development, and even rupture of an aneurysm. We used high-resolution magnetic resonance imaging (HRMRI) to investigate the aneurysm wall in an effort to identify evidence of inflammation invasion and define its relationship with aneurysm behavior. Patients with intracranial aneurysms who were prospectively evaluated using HRMRI between July 2013 and June 2014 were enrolled in this study. The aneurysm's wall enhancement and evidence of inflammation invasion were determined. In addition, the relationship between aneurysm wall enhancement and aneurysm size and symptoms, including ruptured aneurysms, giant unruputred intracranial aneurysms (UIAs) presenting as mass effect, progressively growing aneurysms, and aneurysms associated with neurological symptoms, was statistically analyzed. Twenty-five patients with 30 aneurysms were available for the current study. Fourteen aneurysms showed wall enhancement, including 6 ruptured and 8 unruptured aneurysms. Evidence of inflammation was identified directly through histological studies and indirectly through intraoperative investigations and clinical courses. The statistical analysis indicated no significant correlation between aneurysm wall enhancement and aneurysm size. However, there was a strong correlation between wall enhancement and aneurysm symptoms, with a kappa value of 0.86 (95 % CI 0.68-1). Aneurysm wall enhancement on HRMRI might be a sign of inflammatory change. Symptomatic aneurysms exhibited wall enhancement on HRMRI. Wall enhancement had a high consistent correlation of symptomatic aneurysms. Therefore, wall enhancement on HRMRI might predict an unsteady state of an intracranial saccular aneurysm.

Systemic delivery of blood-brain barrier-targeted polymeric nanoparticles enhances delivery to brain tissue.

PubMed

Saucier-Sawyer, Jennifer K; Deng, Yang; Seo, Young-Eun; Cheng, Christopher J; Zhang, Junwei; Quijano, Elias; Saltzman, W Mark

2015-01-01

Delivery of therapeutic agents to the central nervous system is a significant challenge, hindering progress in the treatment of diseases such as glioblastoma. Due to the presence of the blood-brain barrier (BBB), therapeutic agents do not readily transverse the brain endothelium to enter the parenchyma. Previous reports suggest that surface modification of polymer nanoparticles (NPs) can improve their ability to cross the BBB, but it is unclear whether the observed enhancements in transport are large enough to enhance therapy. In this study, we synthesized two degradable polymer NP systems surface-modified with ligands previously suggested to improve BBB transport, and tested their ability to cross the BBB after intravenous injection in mice. All the NP preparations were able to cross the BBB, although generally in low amounts (<0.5% of the injected dose), which was consistent with prior reports. One NP produced significantly higher brain uptake (∼0.8% of the injected dose): a block copolymer of polylactic acid and hyperbranched polyglycerol, surface modified with adenosine (PLA-HPG-Ad). PLA-HPG-Ad NPs provided controlled release of camptothecin, killing U87 glioma cells in culture. When administered intravenously in mice with intracranial U87 tumors, they failed to increase survival. These results suggest that enhancing NP transport across the BBB does not necessarily yield proportional pharmacological effects.

Inhibition of indoleamine 2,3-dioxygenase activity enhances the anti-tumour effects of a Toll-like receptor 7 agonist in an established cancer model.

PubMed

Ito, Hiroyasu; Ando, Tatsuya; Arioka, Yuko; Saito, Kuniaki; Seishima, Mitsuru

2015-04-01

Toll-like receptor (TLR) agonists have been shown to have anti-tumour activity in basic research and clinical studies. However, TLR agonist monotherapy does not sufficiently eliminate tumours. Activation of the innate immune response by TLR agonists is effective at driving adaptive immunity via interleukin-12 (IL-12) or IL-1, but is counteracted by the simultaneous induction of immunosuppressive cytokines and other molecules, including IL-10, transforming growth factor-β, and indoleamine 2,3-dioxygenase (IDO). In the present study, we evaluated the anti-cancer effect of the TLR7 agonist, imiquimod (IMQ), in the absence of IDO activity. The administration of IMQ in IDO knockout (KO) mice inoculated with tumour cells significantly suppressed tumour progression compared with that in wild-type (WT) mice, and improved the survival rate. Moreover, injection with IMQ enhanced the tumour antigen-specific T helper type 1 response in IDO-KO mice with tumours. Combination therapy with IMQ and an IDO inhibitor also significantly inhibited tumour growth. Our results indicated that the enhancement of IDO expression with TLR agonists in cancer treatment might impair host anti-tumour immunity while the inhibition of IDO could enhance the therapeutic efficacy of TLR agonists via the increase of T helper type 1 immune response. © 2014 John Wiley & Sons Ltd.

Diagnostic value of brain chronic black holes on T1-weighted MR images in clinically isolated syndromes.

PubMed

Mitjana, Raquel; Tintoré, Mar; Rocca, Maria A; Auger, Cristina; Barkhof, Frederik; Filippi, Massimo; Polman, Chris; Fazekas, Franz; Huerga, Elena; Montalban, Xavier; Rovira, Alex

2014-10-01

Non-enhancing black holes (neBHs) are more common in multiple sclerosis (MS) patients with longer disease durations and progressive disease subtypes. Our aim was to analyse the added value of neBHs in patients with clinically isolated syndromes (CISs) for predicting conversion to clinically definite MS (CDMS). Patients were classified based on the presence or absence of neBHs and on the number of Barkhof-Tintoré (B-T) criteria fulfilled. Dissemination in space (DIS) was defined as the presence of at least three of the four B-T criteria. Dissemination in time (DIT)1 was defined by simultaneous presence of enhancing and non-enhancing lesions. DIT2 was defined by simultaneous presence of neBHs and T2 lesions not apparent on T1-weighted images. Focal T2-hyperintense brain lesions were identified in 87.7% of the 520 CIS patients, and 41.4% of them presented at least one neBH. Patients meeting DIS, DIT1, and DIT2 had a significantly higher rate of conversion to CDMS. After adjusting for DIS, only patients who fulfilled DIT1 preserved a significant increase in CDMS conversion. Non-enhancing black holes in CIS patients are associated with a higher risk of conversion to CDMS. However, the predictive value of this finding is lost when added to the DIS criteria. © The Author(s) 2014.

ENHANCED PRACTICAL PHOTOSYNTHETIC CO2 MITIGATION

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dr. Gregory Kremer; Dr. David J. Bayless; Dr. Morgan Vis

2001-10-15

This report documents significant achievements in the Enhanced Practical Photosynthetic CO{sub 2} Mitigation project during the period from 10/03/2000 through 10/02/2001. Most of the achievements are milestones in our efforts to complete the tasks and subtasks that constitute the project objectives. This is the fourth quarterly report for this project, so it also serves as a year-1 project review. We have made significant progress on our Phase I objectives, and our current efforts are focused on fulfilling these research objectives ''on time'' relative to the project timeline. Overall, we believe that we are on schedule to complete Phase I activitiesmore » by 10/2002, which is the milestone date from the original project timeline. Our results to date concerning the individual factors which have the most significant effect on CO{sub 2} uptake are inconclusive, but we have gathered useful information about the effects of lighting, temperature and CO{sub 2} concentration on one particular organism (Nostoc) and significant progress has been made in identifying other organisms that are more suitable for use in the bioreactor due to their better tolerance for the high temperatures likely to be encountered in the flue gas stream. Our current tests are focused on one such thermophilic organism (Cyanidium), and an enlarged bioreactor system (CRF-2) has been prepared for testing this organism. Tests on the enhanced mass transfer CO{sub 2} absorption technique are underway and useful information is currently being collected concerning pressure drop. The solar collectors for the deep-penetration hybrid solar lighting system have been designed and a single solar collector tracking unit is being prepared for installation in the pilot scale bioreactor system currently under construction. Much progress has been made in designing the fiber optic light delivery system, but final selection of the ''optimum'' delivery system design depends on many factors, most significantly the configuration and orientation of the growth surfaces in the bioreactor. For the growth surface subsystem we have identified advantages and disadvantages for several candidate growth surface materials, we have built and tested various ''screen'' systems and fluid delivery systems, and we continue to test compatibility of the candidate materials with the organisms and with the moisture delivery and harvesting system designs. These tests will be ongoing until an ''optimum'' combination of growth surface material/organism type/harvesting system is identified. For the harvesting system, a nozzle-based water jet system has been shown to be effective, but it has disadvantages for the overall system design in terms of space utilization. A streamlined and integrated screen wetting/harvesting system design is currently under development and will be the focus of harvesting system tests in the foreseeable future. This report addresses each of the key project tasks as defined in the statement of work, giving both a summary of key accomplishments over the past year and a plan for future work.« less

Salmonella enterica suppresses Pectobacterium carotovorum subsp. carotovorum population and soft rot progression by acidifying the microaerophilic environment.

PubMed

Kwan, Grace; Charkowski, Amy O; Barak, Jeri D

2013-02-12

Although enteric human pathogens are usually studied in the context of their animal hosts, a significant portion of their life cycle occurs on plants. Plant disease alters the phyllosphere, leading to enhanced growth of human pathogens; however, the impact of human pathogens on phytopathogen biology and plant health is largely unknown. To characterize the interaction between human pathogens and phytobacterial pathogens in the phyllosphere, we examined the interactions between Pectobacterium carotovorum subsp. carotovorum and Salmonella enterica or Escherichia coli O157:H7 with regard to bacterial populations, soft rot progression, and changes in local pH. The presence of P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7 on leaves. However, in a microaerophilic environment, S. enterica reduced P. carotovorum subsp. carotovorum populations and soft rot progression by moderating local environmental pH. Reduced soft rot was not due to S. enterica proteolytic activity. Limitations on P. carotovorum subsp. carotovorum growth, disease progression, and pH elevation were not observed on leaves coinoculated with E. coli O157:H7 or when leaves were coinoculated with S. enterica in an aerobic environment. S. enterica also severely undermined the relationship between the phytobacterial population and disease progression of a P. carotovorum subsp. carotovorum budB mutant defective in the 2,3-butanediol pathway for acid neutralization. Our results show that S. enterica and E. coli O157:H7 interact differently with the enteric phytobacterial pathogen P. carotovorum subsp. carotovorum. S. enterica inhibition of soft rot progression may conceal a rapidly growing human pathogen population. Whereas soft rotted produce can alert consumers to the possibility of food-borne pathogens, healthy-looking produce may entice consumption of contaminated vegetables. Salmonella enterica and Escherichia coli O157:H7 may use plants to move between animal and human hosts. Their populations are higher on plants cocolonized with the common bacterial soft rot pathogen Pectobacterium carotovorum subsp. carotovorum, turning edible plants into a risk factor for human disease. We inoculated leaves with P. carotovorum subsp. carotovorum and S. enterica or E. coli O157:H7 to study the interactions between these bacteria. While P. carotovorum subsp. carotovorum enhanced the growth of both S. enterica and E. coli O157:H7, these human pathogens affected P. carotovorum subsp. carotovorum fundamentally differently. S. enterica reduced P. carotovorum subsp. carotovorum growth and acidified the environment, leading to less soft rot on leaves; E. coli O157:H7 had no such effects. As soft rot signals a food safety risk, the reduction of soft rot symptoms in the presence of S. enterica may lead consumers to eat healthy-looking but S. enterica-contaminated produce.

Aberrant Notch1-dependent effects on glomerular parietal epithelial cells promotes collapsing focal segmental glomerulosclerosis with progressive podocyte loss.

PubMed

Ueno, Toshiharu; Kobayashi, Namiko; Nakayama, Makiko; Takashima, Yasutoshi; Ohse, Takamoto; Pastan, Ira; Pippin, Jeffrey W; Shankland, Stuart J; Uesugi, Noriko; Matsusaka, Taiji; Nagata, Michio

2013-06-01

Collapsing focal segmental glomerulosclerosis (cFSGS) is a progressive kidney disease characterized by glomerular collapse with epithelial hyperplasia. Here we used a transgenic mouse model of cFSGS with immunotoxin-induced podocyte-specific injury to determine the role for Notch signaling in its pathogenesis. The mice exhibited progressive loss of podocytes and severe proteinuria concomitant with histological features of cFSGS. Hyperplastic epithelium was negative for genetic podocyte tags, but positive for the parietal epithelial cell marker claudin-1, and expressed Notch1, Jagged1, and Hes1 mRNA and protein. Enhanced Notch mRNA expression induced by transforming growth factor-β1 in cultured parietal epithelial cells was associated with mesenchymal markers (α-smooth muscle actin, vimentin, and Snail1). Notch inhibition in vitro suppressed these phenotypic transcripts and Notch-dependent cell migration. Moreover, Notch inhibition in vivo significantly decreased parietal epithelial cell lesions but worsened proteinuria and histopathology in our cFSGS model. Thus, aberrant Notch1-mediated parietal epithelial cell migration with phenotypic changes appears to underlie the pathogenesis of cFSGS. Parietal epithelial cell hyperplasia may also represent an adaptive response to compensate for a disrupted filtration barrier with progressive podocyte loss.

Effects of exercise on fitness and cognition in progressive MS: a randomized, controlled pilot trial.

PubMed

Briken, S; Gold, S M; Patra, S; Vettorazzi, E; Harbs, D; Tallner, A; Ketels, G; Schulz, K H; Heesen, C

2014-03-01

Exercise may have beneficial effects on both well-being and walking ability in multiple sclerosis (MS). Exercise is shown to be neuroprotective in rodents and may also enhance cognitive function in humans. It may, therefore, be particularly useful for MS patients with pronounced neurodegeneration. To investigate the potential of standardized exercise as a therapeutic intervention for progressive MS, in a randomized-controlled pilot trial. Patients with progressive MS and moderate disability (Expanded Disability Status Scale (EDSS) of 4-6) were randomized to one of three exercise interventions (arm ergometry, rowing, bicycle ergometry) for 8-10 weeks or a waitlist control group. We analyzed the drop-out rate as a measure of feasibility. The primary endpoint of the study was aerobic fitness. Secondary endpoints were walking ability, cognitive function as measured by a neuropsychological test battery, depression and fatigue. A total of 42 patients completed the trial (10.6% drop-out rate). Significant improvements were seen in aerobic fitness. In addition, exercise improved walking ability, depressive symptoms, fatigue and several domains of cognitive function. This study indicated that aerobic training is feasible and could be beneficial for patients with progressive MS. Larger exercise studies are needed to confirm the effect on cognition. ISRCTN (trial number 76467492) http://isrctn.org.

Validation of dynamic contrast-enhanced ultrasound in predicting outcomes of antiangiogenic therapy for solid tumors: the French multicenter support for innovative and expensive techniques study.

PubMed

Lassau, Nathalie; Bonastre, Julia; Kind, Michèle; Vilgrain, Valérie; Lacroix, Joëlle; Cuinet, Marie; Taieb, Sophie; Aziza, Richard; Sarran, Antony; Labbe-Devilliers, Catherine; Gallix, Benoit; Lucidarme, Olivier; Ptak, Yvette; Rocher, Laurence; Caquot, Louis-Michel; Chagnon, Sophie; Marion, Denis; Luciani, Alain; Feutray, Sylvaine; Uzan-Augui, Joëlle; Coiffier, Benedicte; Benastou, Baya; Koscielny, Serge

2014-12-01

Dynamic contrast-enhanced ultrasound (DCE-US) has been used in single-center studies to evaluate tumor response to antiangiogenic treatments: the change of area under the perfusion curve (AUC), a criterion linked to blood volume, was consistently correlated with the Response Evaluation Criteria in Solid Tumors response. The main objective here was to do a multicentric validation of the use of DCE-US to evaluate tumor response in different solid tumor types treated by several antiangiogenic agents. A secondary objective was to evaluate the costs of the procedure. This prospective study included patients from 2007 to 2010 in 19 centers (8 teaching hospitals and 11 comprehensive cancer centers). All patients treated with antiangiogenic therapy were eligible. Dynamic contrast-enhanced ultrasound examinations were performed at baseline as well as on days 7, 15, 30, and 60. For each examination, a perfusion curve was recorded during 3 minutes after injection of a contrast agent. Change from baseline at each time point was estimated for each of 7 fitted criteria. The main end point was freedom from progression (FFP). Criterion/time-point combinations with the strongest correlation with FFP were analyzed further to estimate an optimal cutoff point. A total of 1968 DCE-US examinations in 539 patients were analyzed. The median follow-up was 1.65 years. Variations from baseline were significant at day 30 for several criteria, with AUC having the most significant association with FFP (P = 0.00002). Patients with a greater than 40% decrease in AUC at day 30 had better FFP (P = 0.005) and overall survival (P = 0.05). The mean cost of each DCE-US was 180&OV0556;, which corresponds to $250 using the current exchange rate. Dynamic contrast-enhanced ultrasound is a new functional imaging technique that provides a validated criterion, namely, the change of AUC from baseline to day 30, which is predictive of tumor progression in a large multicenter cohort. Because of its low cost, it should be considered in the routine evaluation of solid tumors treated with antiangiogenic therapy.

Progress in performance enhancement methods for capacitive silicon resonators

NASA Astrophysics Data System (ADS)

Van Toan, Nguyen; Ono, Takahito

2017-11-01

In this paper, we review the progress in recent studies on the performance enhancement methods for capacitive silicon resonators. We provide information on various fabrication technologies and design considerations that can be employed to improve the performance of capacitive silicon resonators, including low motional resistance, small insertion loss, and high quality factor (Q). This paper contains an overview of device structures and working principles, fabrication technologies consisting of hermetic packaging, deep reactive-ion etching and neutral beam etching, and design considerations including mechanically coupled, movable electrode structures and piezoresistive heat engines.

Does Computed Tomography Have the Ability to Differentiate Aggressive From Nonaggressive Solid Pseudopapillary Neoplasm?

PubMed

Rastogi, Ashita; Assing, Mathew; Taggart, Mellisa; Rao, Brinda; Sun, Jia; Elsayes, Khaled; Tamm, Eric; Bhosale, Priya

The aim of the study was to assess the ability of contrast-enhanced computed tomography (CECT) to differentiate aggressive from nonaggressive solid pseudopapillary neoplasms (SPNs). Forty treatment-naive patients with pathologically proven pancreatic SPNs were included. Imaging characteristics were determined by consensus of 3 radiologists blinded to histopathologic aggressiveness. All patients underwent 4-phase CECT using a pancreatic protocol. The regions of interest of the tumor and the normal pancreas were documented on all phases. Lymph nodes were considered metastatic if greater than 1.0 cm in short-axis diameter.Fisher exact and Wilcoxon rank-sum tests were used to compare between aggressive and nonaggressive tumors. No significant difference was noted between imaging covariates, such as internal hemorrhage, calcification, wall thickness perceptibility, vascular invasion, margins, cystic component, and pancreatic and biliary ductal dilation. Tumors with greater than 62.5 Hounsfield units and progressive enhancement during the delayed phase had aggressive characteristics (P = 0.03). On delayed phase CECT, pathologically aggressive SPNs may show greater enhancement than nonaggressive SPNs.

Resveratrol enhances HBV replication through activating Sirt1-PGC-1α-PPARα pathway.

PubMed

Shi, Yixian; Li, Yongjun; Huang, Chenjie; Ying, Lixiong; Xue, Jihua; Wu, Haicong; Chen, Zhi; Yang, Zhenggang

2016-04-21

The population of hepatitis B combined with a number of metabolic disorders is increasing significantly. Resveratrol (RSV) has been used as a preclinical drug for the treatment of the metabolic disorders. However, the impact of RSV on HBV replication remains unknown. In this study, the HBV-expressing hepatocelluar carcinoma cell line and mouse model created by hydrodynamic injection of viral DNA were used. We found that RSV activates Sirt1, which in turn deacetylates PGC-1α and subsequently increases the transcriptional activity of PPARα, leading to the enhanced HBV transcription and replication in vitro and in vivo. In addition, we found that this pathway is also required for fasting-induced HBV transcription. Taken together, this study identifies that RSV enhances HBV transcription and replication especially acting on the core promoter, which depends on Sirt1-PGC-1α-PPARα pathway. We conclude that RSV may exacerbate the progression of hepatitis B and that patients with hepatitis B infection should be cautious taking RSV as a dietary supplement.

Overexpression of Cullin7 is associated with hepatocellular carcinoma progression and pathogenesis.

PubMed

An, Jun; Zhang, Zhigang; Liu, Zhiyong; Wang, Ruizhi; Hui, Dayang; Jin, Yi

2017-12-06

Overexpression of Cullin7 is associated with some types of malignancies. However, the part of Cullin7 in hepatocellular carcinoma remains unclear. The aim of this study was to investigate the role of Cullin7 in pathogenesis and the progression of hepatocellular carcinoma. In the present study, the expression of Cullin7 in hepatocellular carcinoma cell lines and five surgical hepatocellular carcinoma specimens was detected with quantitative reverse transcription PCR and western blotting. In addition, the protein expression of Cullin7 was examined in 162 cases of archived hepatocellular carcinoma using immunohistochemistry. We found elevated expression of both mRNA and protein levels of Cullin7 in hepatocellular carcinoma cell lines, and Cullin7 protein was significantly upregulated in hepatocellular carcinoma compared with paired normal hepatic tissues. The immunohistochemistry analysis revealed that overexpression of Cullin7 occurred in 69.1% of hepatocellular carcinoma samples, which was a significantly higher rate than that in adjacent normal hepatic tissue (P < 0.01). Statistical analysis found that overexpression of Cullin7 was significantly associated with lymph node metastasis, tumor thrombus of the portal vein and advanced clinical stage (P < 0.05). Furthermore, by overexpressing Cullin7 in hepatocellular carcinoma HepG2 cells, we revealed that Cullin7 could significantly enhance cell proliferation, growth, migration and invasion. Conversely, knocking down Cullin7 expression with short hairpin RNAi in hepatocellular carcinoma HepG2 cells inhibited cell proliferation, growth, migration and invasion. Our studies provide evidence that overexpression of Cullin7 plays an important role in the pathogenesis and progression of hepatocellular carcinoma and may be a valuable marker for hepatocellular carcinoma management.

Psychotherapy for Borderline Personality Disorder: Progress and Remaining Challenges.

PubMed

Links, Paul S; Shah, Ravi; Eynan, Rahel

2017-03-01

The main purpose of this review was to critically evaluate the literature on psychotherapies for borderline personality disorder (BPD) published over the past 5 years to identify the progress with remaining challenges and to determine priority areas for future research. A systematic review of the literature over the last 5 years was undertaken. The review yielded 184 relevant abstracts, and after applying inclusion criteria, 16 articles were fully reviewed based on the articles' implications for future research and/or clinical practice. Our review indicated that patients with various severities benefited from psychotherapy; more intensive therapies were not significantly superior to less intensive therapies; enhancing emotion regulation processes and fostering more coherent self-identity were important mechanisms of change; therapies had been extended to patients with BPD and posttraumatic stress disorder; and more research was needed to be directed at functional outcomes.

Enhancing the Health-Promoting Effects of Tomato Fruit for Biofortified Food

PubMed Central

Rigano, Maria Manuela; Frusciante, Luigi; Barone, Amalia

2014-01-01

Consumption of tomato fruits, like those of many other plant species that are part of the human diet, is considered to be associated with several positive effects on health. Indeed, tomato fruits are an important source of bioactive compounds with known beneficial effects including vitamins, antioxidants, and anticancer substances. In particular, antioxidant metabolites are a group of vitamins, carotenoids, phenolic compounds, and phenolic acid that can provide effective protection by neutralizing free radicals, which are unstable molecules linked to the development of a number of degenerative diseases and conditions. In this review, we will summarize the recent progress on tomatoes nutritional importance and mechanisms of action of different phytochemicals against inflammation processes and prevention of chronic noncommunicable diseases (e.g., obesity, diabetes, coronary heart disease, and hypertension). In addition, we will summarize the significant progress recently made to improve the nutritional quality of tomato fruits through metabolic engineering and/or breeding. PMID:24744504

Children's Interstitial and Diffuse Lung Disease. Progress and Future Horizons.

PubMed

Deterding, Robin R

2015-10-01

Children's interstitial and diffuse lung disease (chILD) is a term that encompasses a large and diverse group of rare pediatric diseases and disorders. Significant progress has been made over the last 2 decades in classification, clinical care, research, and organizational structure to enhance the care of children with these high-morbidity and -mortality diseases. New diseases have been defined clinically and genetically, classification systems developed and applied, organizations formed such as the chILD Research Network (chILDRN) and chILD Foundation, and basic and translational science expanded to focus on chILD diseases. Multidisciplinary collaborations and efforts to advance understanding and treatment of chILD have been extended worldwide. The future horizon holds great promise to expand scientific discoveries, collaborate more broadly, and bring new treatment to these children. An overview of key historical past developments, major clinical and research updates, and opportunities for the future in chILD is reviewed in this Perspective.

Complex problems and unchallenged solutions: Bringing ecosystem governance to the forefront of the UN sustainable development goals.

PubMed

Vasseur, Liette; Horning, Darwin; Thornbush, Mary; Cohen-Shacham, Emmanuelle; Andrade, Angela; Barrow, Ed; Edwards, Steve R; Wit, Piet; Jones, Mike

2017-11-01

Sustainable development aims at addressing economic, social, and environmental concerns, but the current lack of responsive environmental governance hinders progress. Short-term economic development has led to limited actions, unsustainable resource management, and degraded ecosystems. The UN Sustainable Development Goals (SDGs) may continue to fall short of achieving significant progress without a better understanding of how ecosystems contribute to achieving sustainability for all people. Ecosystem governance is an approach that integrates the social and ecological components for improved sustainability and includes principles such as adaptive ecosystem co-management, subsidiarity, and telecoupling framework, as well as principles of democracy and accountability. We explain the importance of ecosystem governance in achieving the SDGs, and suggest some ways to ensure that ecosystem services are meaningfully considered. This paper reflects on how integration of these approaches into policies can enhance the current agenda of sustainability.

Managers' roles in the professional growth of Iranian clinical nurses.

PubMed

Rahimaghaee, Flora; Nayeri, Nahid Dehghan; Mohammadi, Eesa

2010-12-01

Any progressive organization should consider investing in its clinical nurses' professional growth if it desires to survive and succeed in offering care. Managers play a significant role in facilitating clinical nurses' professional growth. A content analysis study was conducted with 20 clinical nurses and managers in Iran in order to describe how they experienced managers' roles in relation to their professional growth. They believed that managers played two major roles in their professional growth process: motivating and inhibiting. From the participants' point of view, managers, through supporting, encouraging, and valuing staff and creating opportunities for learning, played a facilitating role in their professional growth. But, whenever the staff did not receive this support, they became discouraged and did not make any progress. The results can be used to improve management and, consequently, to enhance the professional growth of staff. © 2010 Blackwell Publishing Asia Pty Ltd.

Drug-based modulation of endogenous stem cells promotes functional remyelination in vivo

PubMed Central

Najm, Fadi J.; Madhavan, Mayur; Zaremba, Anita; Shick, Elizabeth; Karl, Robert T.; Factor, Daniel C.; Miller, Tyler E.; Nevin, Zachary S.; Kantor, Christopher; Sargent, Alex; Quick, Kevin L.; Schlatzer, Daniela M.; Tang, Hong; Papoian, Ruben; Brimacombe, Kyle R.; Shen, Min; Boxer, Matthew B.; Jadhav, Ajit; Robinson, Andrew P.; Podojil, Joseph R.; Miller, Stephen D.; Miller, Robert H.; Tesar, Paul J.

2015-01-01

Multiple sclerosis (MS) involves an aberrant autoimmune response and progressive failure of remyelination in the central nervous system (CNS). Prevention of neural degeneration and subsequent disability requires remyelination through the generation of new oligodendrocytes, but current treatments exclusively target the immune system. Oligodendrocyte progenitor cells (OPCs) are stem cells in the CNS and the principal source of myelinating oligodendrocytes1. OPCs are abundant in demyelinated regions of MS patients, yet fail to differentiate, thereby representing a cellular target for pharmacological intervention2. To discover therapeutic compounds for enhancing myelination from endogenous OPCs, we screened a library of bioactive small molecules on mouse pluripotent epiblast stem cell (EpiSC)-derived OPCs3–5. We identified seven drugs that functioned at nanomolar doses to selectively enhance the generation of mature oligodendrocytes from OPCs in vitro. Two drugs, miconazole and clobetasol, were effective in promoting precocious myelination in organotypic cerebellar slice cultures, and in vivo in early postnatal mouse pups. Systemic delivery of each of the two drugs significantly increased the number of new oligodendrocytes and enhanced remyelination in a lysolecithin-induced mouse model of focal demyelination. Administering each of the two drugs at the peak of disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of chronic progressive MS resulted in striking reversal of disease severity. Immune response assays showed that miconazole functioned directly as a remyelinating drug with no effect on the immune system, whereas clobetasol was a potent immunosuppressant as well as a remyelinating agent. Mechanistic studies showed that miconazole and clobetasol functioned in OPCs through mitogen-activated protein kinase (MAPK) and glucocorticoid receptor (GR) signaling, respectively. Furthermore, both drugs enhanced the generation of human oligodendrocytes from human OPCs in vitro. Collectively, our results provide a rationale for testing miconazole and clobetasol, or structurally-modified derivatives, to enhance remyelination in patients. PMID:25896324

A Framework for Reproducible Latent Fingerprint Enhancements.

PubMed

Carasso, Alfred S

2014-01-01

Photoshop processing of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology.

A Framework for Reproducible Latent Fingerprint Enhancements

PubMed Central

Carasso, Alfred S.

2014-01-01

Photoshop processing1 of latent fingerprints is the preferred methodology among law enforcement forensic experts, but that appproach is not fully reproducible and may lead to questionable enhancements. Alternative, independent, fully reproducible enhancements, using IDL Histogram Equalization and IDL Adaptive Histogram Equalization, can produce better-defined ridge structures, along with considerable background information. Applying a systematic slow motion smoothing procedure to such IDL enhancements, based on the rapid FFT solution of a Lévy stable fractional diffusion equation, can attenuate background detail while preserving ridge information. The resulting smoothed latent print enhancements are comparable to, but distinct from, forensic Photoshop images suitable for input into automated fingerprint identification systems, (AFIS). In addition, this progressive smoothing procedure can be reexamined by displaying the suite of progressively smoother IDL images. That suite can be stored, providing an audit trail that allows monitoring for possible loss of useful information, in transit to the user-selected optimal image. Such independent and fully reproducible enhancements provide a valuable frame of reference that may be helpful in informing, complementing, and possibly validating the forensic Photoshop methodology. PMID:26601028

Secretory leukocyte protease inhibitor gene deletion alters bleomycin-induced lung injury, but not development of pulmonary fibrosis.

PubMed

Habgood, Anthony N; Tatler, Amanda L; Porte, Joanne; Wahl, Sharon M; Laurent, Geoffrey J; John, Alison E; Johnson, Simon R; Jenkins, Gisli

2016-06-01

Idiopathic pulmonary fibrosis is a progressive, fatal disease with limited treatment options. Protease-mediated transforming growth factor-β (TGF-β) activation has been proposed as a pathogenic mechanism of lung fibrosis. Protease activity in the lung is tightly regulated by protease inhibitors, particularly secretory leukocyte protease inhibitor (SLPI). The bleomycin model of lung fibrosis was used to determine the effect of increased protease activity in the lungs of Slpi(-/-) mice following injury. Slpi(-/-), and wild-type, mice received oropharyngeal administration of bleomycin (30 IU) and the development of pulmonary fibrosis was assessed. Pro and active forms of matrix metalloproteinase (MMP)-2 and MMP-9 were measured. Lung fibrosis was determined by collagen subtype-specific gene expression, hydroxyproline concentration, and histological assessment. Alveolar TGF-β activation was measured using bronchoalveolar lavage cell pSmad2 levels and global TGF-β activity was assessed by pSmad2 immunohistochemistry. The active-MMP-9 to pro-MMP-9 ratio was significantly increased in Slpi(-/-) animals compared with wild-type animals, demonstrating enhanced metalloproteinase activity. Wild-type animals showed an increase in TGF-β activation following bleomycin, with a progressive and sustained increase in collagen type I, alpha 1 (Col1α1), III, alpha 1(Col3α1), IV, alpha 1(Col4α1) mRNA expression, and a significant increase in total lung collagen 28 days post bleomycin. In contrast Slpi(-/-) mice showed no significant increase of alveolar TGF-β activity following bleomycin, above their already elevated levels, although global TGF-β activity did increase. Slpi(-/-) mice had impaired collagen gene expression but animals demonstrated minimal reduction in lung fibrosis compared with wild-type animals. These data suggest that enhanced proteolysis does not further enhance TGF-β activation, and inhibits sustained Col1α1, Col3α1, and Col4α1 gene expression following lung injury. However, these changes do not prevent the development of lung fibrosis. Overall, these data suggest that the absence of Slpi does not markedly modify the development of lung fibrosis following bleomycin-induced lung injury.

Targeting demyelination and virtual hypoxia with high-dose biotin as a treatment for progressive multiple sclerosis.

PubMed

Sedel, Frédéric; Bernard, Delphine; Mock, Donald M; Tourbah, Ayman

2016-11-01

Progressive multiple sclerosis (MS) is a severely disabling neurological condition, and an effective treatment is urgently needed. Recently, high-dose biotin has emerged as a promising therapy for affected individuals. Initial clinical data have shown that daily doses of biotin of up to 300 mg can improve objective measures of MS-related disability. In this article, we review the biology of biotin and explore the properties of this ubiquitous coenzyme that may explain the encouraging responses seen in patients with progressive MS. The gradual worsening of neurological disability in patients with progressive MS is caused by progressive axonal loss or damage. The triggers for axonal loss in MS likely include both inflammatory demyelination of the myelin sheath and primary neurodegeneration caused by a state of virtual hypoxia within the neuron. Accordingly, targeting both these pathological processes could be effective in the treatment of progressive MS. Biotin is an essential co-factor for five carboxylases involved in fatty acid synthesis and energy production. We hypothesize that high-dose biotin is exerting a therapeutic effect in patients with progressive MS through two different and complementary mechanisms: by promoting axonal remyelination by enhancing myelin production and by reducing axonal hypoxia through enhanced energy production. This article is part of the Special Issue entitled 'Oligodendrocytes in Health and Disease'. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

TRENDS IN USE OF EZETIMIBE AFTER THE ENHANCE TRIAL, 2007–2010

PubMed Central

Ross, Joseph S.; Frazee, Sharon G.; Garavaglia, Susan B.; Levin, Rebecca; Novshadian, Haik; Jackevicius, Cynthia A.; Stettin, Glen; Krumholz, Harlan M.

2014-01-01

Importance Results from the landmark Ezetimibe and Simvastatin in Hypercholesterolemia Enhances Atherosclerosis Regression [ENHANCE] trial were announced in January 2008, demonstrating that ezetimibe lowered cholesterol levels but did not slow the progression of atherosclerosis. Objective Examine the association of this announcement with national patterns of ezetimibe prescribing, including medication initiation and discontinuation, as well as predictors of use. Design, Setting and Patients Retrospective analysis of a national sample of adults aged 18 years or older who were continuously enrolled in a large U.S. pharmacy benefit manager from 2007 to 2010. Main Outcome Measures All lipid-lowering therapy prescription claims were categorized as ezetimibe-containing treatments or any other lipid-lowering agent. Initiation was defined as an ezetimibe claim without another in the prior 180 days; discontinuation as an ezetimibe claim without another in the subsequent 180 days. Results From 2007 to 2010, there were 10 million continuously eligible adults, 29.1% of whom obtained at least one prescription for a lipid-lowering agent. Among these adults, 17.8% were prescribed ezetimibe, 95.3% another lipid-lowering agent, predominantly statins. Ezetimibe use peaked in January 2008, when 2.5% of all adults were ezetimibe users, but declined only to 1.8% by December 2010. Although announcement of the ENHANCE trial was not associated with a significant change in overall ezetimibe use (p=0.11), it was associated with significantly more monthly monotherapy use and significantly less monthly ezetimibe use concomitant with other lipid-lowering agents. The ENHANCE trial was also associated with significantly fewer ezetimibe initiations (p=0.002) and significantly more ezetimibe discontinuations (p<0.0001), particularly of ezetimibe monotherapy for both. Before and after the trial, more than half of adults who initiated ezetimibe did so without first being prescribed another lipid-lowering agent. Middle aged adults (50 and 64 years) and those living in the East South Central United States were both more likely to initiate and less likely to discontinue ezetimibe after the ENHANCE trial. Conclusions After announcement of the results of the ENHANCE trial, nearly 2% of all continuously enrolled adult beneficiaries within a large U.S. pharmacy benefit manager used ezetimibe, although ezetimibe initiations declined and discontinuations increased. PMID:25070672

Sequential contrast-enhanced MR imaging of the penis.

PubMed

Kaneko, K; De Mouy, E H; Lee, B E

1994-04-01

To determine the enhancement patterns of the penis at magnetic resonance (MR) imaging. Sequential contrast material-enhanced MR images of the penis in a flaccid state were obtained in 16 volunteers (12 with normal penile function and four with erectile dysfunction). Subjects with normal erectile function showed gradual and centrifugal enhancement of the corpora cavernosa, while those with erectile dysfunction showed poor enhancement with abnormal progression. Sequential contrast-enhanced MR imaging provides additional morphologic information for the evaluation of erectile dysfunction.

Towards optimizing the sequence of bevacizumab and nitrosoureas in recurrent malignant glioma.

PubMed

Wiestler, Benedikt; Radbruch, Alexander; Osswald, Matthias; Combs, Stephanie E; Jungk, Christine; Winkler, Frank; Bendszus, Martin; Unterberg, Andreas; Platten, Michael; Wick, Wolfgang; Wick, Antje

2014-03-01

Studies on the monoclonal VEGF-A antibody bevacizumab gave raise to questions regarding the lack of an overall survival benefit, the optimal timing in the disease course and potential combination and salvage therapies. We retrospectively assessed survival, radiological progression type on bevacizumab and efficacy of salvage therapies in 42 patients with recurrent malignant gliomas who received bevacizumab and nitrosourea sequentially. 15 patients received bevacizumab followed by nitrosourea at progression and 27 patients vice versa. Time to treatment failure, defined as time from initiation of one to failure of the other treatment, was similar in both groups (9.6 vs. 9.2 months, log rank p = 0.19). Progression-free survival on nitrosoureas was comparable in both groups, while progression-free survival on bevacizumab was longer in the group receiving bevacizumab first (5.3 vs. 4.1 months, log rank p = 0.03). Survival times were similar for patients with grade III (n = 9) and grade IV (n = 33) tumors. Progression-free survival on bevacizumab for patients developing contrast-enhancing T1 progression was longer than for patients who displayed a non-enhancing T2 progression. However, post-progression survival times after bevacizumab failure were not different. Earlier treatment with bevacizumab was not associated with better outcome in this series. The fact that earlier as compared to later bevacizumab treatment does not result in a different time to treatment failure highlights the challenge for first-line or recurrence trials with bevacizumab to demonstrate an overall survival benefit if crossover of bevacizumab-naïve patients after progression occurs.

Progressing MoodSwings. The upgrade and evaluation of MoodSwings 2.0: An online intervention for bipolar disorder.

PubMed

Lauder, S; Cosgrove, V E; Gliddon, E; Grimm, D; Dodd, S; Berk, L; Castle, D; Suppes, T S; Berk, M

2017-05-01

MoodSwings 2.0 is a self-guided online intervention for bipolar disorder. The intervention incorporates technological improvements on an earlier validated version of the intervention (MoodSwings 1.0). The previous MoodSwings trial provides this study with a unique opportunity to progress previous work, whilst being able to take into consideration lesson learnt, and technological enhancements. The structure and technology of MoodSwings 2.0 are described and the relevance to other online health interventions is highlighted. An international team from Australia and the US updated and improved the programs content pursuant to changes in DSM-5, added multimedia components and included larger numbers of participants in the group discussion boards. Greater methodological rigour in this trial includes an attention control condition, quarterly telephone assessments, and red flag alerts for significant clinical change. This paper outlines these improvements, including additional security and safety measures. A 3 arm RCT is currently evaluating the enhanced program to assess the efficacy of MS 2.0; the primary outcome is change in depressive and manic symptoms. To our knowledge this is the first randomized controlled online bipolar study with a discussion board attention control and meets the key methodological criteria for online interventions. Copyright © 2017. Published by Elsevier Inc.

Progressing MoodSwings. The upgrade and evaluation of MoodSwings 2.0: An online intervention for Bipolar Disorder

PubMed Central

Lauder, S.; Cosgrove, V.E.; Gliddon, E.; Grimm, D.; Dodd, S.; Berk, L.; Castle, D.; Suppes, T.S.; Berk, M.

2017-01-01

MoodSwings 2.0 is a self-guided online intervention for bipolar disorder. The intervention incorporates technological improvements on an earlier validated version of the intervention (MoodSwings 1.0). The previous MoodSwings trial provides this study with a unique opportunity to progress previous work, whilst being able to take into consideration lesson learnt, and technological enhancements. The structure and technology of MoodSwings 2.0 are described and the relevance to other online health interventions is highlighted. An international team from Australia and the US updated and improved the programs content pursuant to changes in DSM-5, added multimedia components and included larger numbers of participants in the group discussion boards. Greater methodological rigour in this trial includes an attention control condition, quarterly telephone assessments, and red flag alerts for significant clinical change. This paper outlines these improvements, including additional security and safety measures. A 3 arm RCT is currently evaluating the enhanced program to assess the efficacy of MS 2.0; the primary outcome is change in depressive and manic symptoms. To our knowledge this is the first randomised controlled online bipolar study with a discussion board attention control and meets the key methodological criteria for online interventions PMID:28257919

Design, Fabrication, and In Vitro Testing of an Anti-biofouling Glaucoma Micro-shunt.

PubMed

Harake, Ryan S; Ding, Yuzhe; Brown, J David; Pan, Tingrui

2015-10-01

Glaucoma, one of the leading causes of irreversible blindness, is a progressive neurodegenerative disease. Chronic elevated intraocular pressure (IOP), a prime risk factor for glaucoma, can be treated by aqueous shunts, implantable devices, which reduce IOP in glaucoma patients by providing alternative aqueous outflow pathways. Although initially effective at delaying glaucoma progression, contemporary aqueous shunts often lead to numerous complications and only 50% of implanted devices remain functional after 5 years. In this work, we introduce a novel micro-device which provides an innovative platform for IOP reduction in glaucoma patients. The device design features an array of parallel micro-channels to provide precision aqueous outflow resistance control. Additionally, the device's microfluidic channels are composed of a unique combination of polyethylene glycol materials in order to provide enhanced biocompatibility and resistance to problematic channel clogging from biofouling of aqueous proteins. The microfabrication process employed to produce the devices results in additional advantages such as enhanced device uniformity and increased manufacturing throughput. Surface characterization experimental results show the device's surfaces exhibit significantly less non-specific protein adsorption compared to traditional implant materials. Results of in vitro flow experiments verify the device's ability to provide aqueous resistance control, continuous long-term stability through 10-day protein flow testing, and safety from risk of infection due to bacterial ingression.

O-GlcNAcylation enhances anaplastic thyroid carcinoma malignancy.

PubMed

Cheng, Y U; Li, Honglun; Li, Jianlin; Li, Jisheng; Gao, Yan; Liu, Baodong

2016-07-01

O-linked N -acetylglucosamine (O-GlcNAc) glycosylation (O-GlcNAcylation), a dynamic post-translational modification of nuclear and cytoplasmic proteins, may have a critical role in the regulation of biological cell processes and human cancer. O-GlcNAcylation is dynamically regulated by O-GlcNAc transferase (OGT) and O-GlcNAc hydrolase (OGA). Accumulating evidence suggests that O-GlcNAcylation is involved in a variety of types of human cancer. However, the exact role of O-GlcNAcylation in tumor pathogenesis or progression remains to be established. Computed tomography scans of patients with anaplastic thyroid carcinoma (ATC) reveal a rapid growth rate and invasion. The present study demonstrated that O-GlcNAcylation accelerates the progression of ATC. The global O-GlcNAc level of intracellular proteins was increased by overexpression of OGT or downregulation of OGA activity with the specific inhibitor Thiamet-G. By contrast, the global O-GlcNAc level was decreased by silencing of OGT. MTT assay indicated that O-GlcNAcylation significantly promotes cell proliferation. Furthermore, O-GlcNAcylation enhanced cellular biological functions, such as colony formation ability, migration and invasion, of ATC cells in vitro . The findings of the present study suggest that O-GlcNAcylation is associated with malignant properties of thyroid cancer, and may be a potential target for the diagnosis and treatment of thyroid cancer.

HER3 expression is enhanced during progression of lung adenocarcinoma without EGFR mutation from stage 0 to IA1.

PubMed

Kumagai, Toru; Tomita, Yasuhiko; Nakatsuka, Shin-Ichi; Kimura, Madoka; Kunimasa, Kei; Inoue, Takako; Tamiya, Motohiro; Nishino, Kazumi; Susaki, Yoshiyuki; Kusu, Takashi; Tokunaga, Toshiteru; Okami, Jiro; Higashiyama, Masahiko; Imamura, Fumio

2018-04-01

Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence of EGFR mutation from stage 0 to IA1. HER2 and HER3 expression and activating EGFR mutations in surgically resected lung adenocarcinoma exhibiting ground glass nodules on chest computed tomography and re-classified to stage 0 and IA1 were examined by immunohistochemistry and peptide nucleic acid-locked nucleic acid PCR clamp method, respectively. HER2 and HER3 expression was detected in 22.2% and 86.1% of samples, respectively. The frequency of EGFR mutation was 45.7% and was not significantly different between stage 0 and IA1 (40.0% and 48.0%, respectively), suggesting that EGFR mutation does not correlate with cancer progression from stage 0 to IA1. HER2 expression also did not correlate to progression. However, not only the frequency, but also the intensity of HER3 expression was increased in stage IA1 lung adenocarcinoma, particularly in lung adenocarcinoma without EGFR mutation. HER3 tends to be intensively expressed during the progression of lung adenocarcinoma without EGFR mutation from carcinoma in situ to invasive carcinoma. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

Patterns of relapse and prognosis after bevacizumab failure in recurrent glioblastoma

PubMed Central

Iwamoto, F M.; Abrey, L E.; Beal, K; Gutin, P H.; Rosenblum, M K.; Reuter, V E.; DeAngelis, L M.; Lassman, A B.

2009-01-01

Background: Bevacizumab has recently been approved by the US Food and Drug Administration for recurrent glioblastoma (GBM). However, patterns of relapse, prognosis, and outcome of further therapy after bevacizumab failure have not been studied systematically. Methods: We identified patients at Memorial Sloan-Kettering Cancer Center with recurrent GBM who discontinued bevacizumab because of progressive disease. Results: There were 37 patients (26 men with a median age of 54 years). The most common therapies administered concurrently with bevacizumab were irinotecan (43%) and hypofractionated reirradiation (38%). The median overall survival (OS) after progressive disease on bevacizumab was 4.5 months; 34 patients died. At the time bevacizumab was discontinued for tumor progression, 17 patients (46%) had an increase in the size of enhancement at the initial site of disease (local recurrence), 6 (16%) had a new enhancing lesion outside of the initial site of disease (multifocal), and 13 (35%) had progression of predominantly nonenhancing tumor. Factors associated with shorter OS after discontinuing bevacizumab were lower performance status and nonenhancing pattern of recurrence. Additional salvage chemotherapy after bevacizumab failure was given to 19 patients. The median progression-free survival (PFS) among these 19 patients was 2 months, the median OS was 5.2 months, and the 6-month PFS rate was 0%. Conclusions: Contrast enhanced MRI does not adequately assess disease status during bevacizumab therapy for recurrent glioblastoma (GBM). A nonenhancing tumor pattern of progression is common after treatment with bevacizumab for GBM and is correlated with worse survival. Treatments after bevacizumab failure provide only transient tumor control. GLOSSARY CA9 = carbonic anhydrase 9; CI = confidence interval; FDG = [18F]fluorodeoxyglucose; FLAIR = fluid-attenuation inversion recovery; GBM = glioblastoma; HIF-1 α = hypoxia-inducible factor 1α; KPS = Karnofsky performance status; MR = magnetic resonance; OS = overall survival; PFS = progression-free survival; TMZ = temozolomide; VEGF = vascular endothelial growth factor; VEGFR = vascular endothelial growth factor receptor. PMID:19822869

Treatment of children with recurrent high grade gliomas with a bevacizumab containing regimen.

PubMed

Parekh, Chintan; Jubran, Rima; Erdreich-Epstein, Anat; Panigrahy, Ashok; Bluml, Stefan; Finlay, Jonathan; Dhall, Girish

2011-07-01

Children with recurrent high grade gliomas (HGG) have a dismal outcome with a median progression free survival (PFS) of 12 weeks. Adults with recurrent HGG treated with irinotecan and bevacizumab reportedly have a 63% response rate and a median PFS of 23 weeks. There is a paucity of corresponding published pediatric data. We retrospectively reviewed the records of patients less than 21 years of age with recurrent or progressive WHO grade 3-4 gliomas who were treated with bevacizumab containing regimens at our institution between January 2006 and September 2008. We identified eight patients. Six out of eight patients received irinotecan, temozolomide and bevacizumab, one patient received irinotecan and bevacizumab, and one patient received CCNU and bevacizumab. Three patients had stable disease for 30-93 weeks. The remaining five patients developed progressive disease within 17 weeks. The median PFS was 15 weeks and the 6-month PFS was 38%. Contrast enhancing disease responded or remained stable in five out of seven patients whereas non-enhancing disease progressed in three out of four patients. New distant non-enhancing lesions developed in three patients. The most common side effects included diarrhea, vomiting, thrombocytopenia and neutropenia. Bevacizumab was well tolerated when used in combination with conventional chemotherapy (irinotecan in most cases). PFS in our cohort was much shorter and the response rate was inferior in this small cohort of patients when compared with published adult data. However, bevacizumab containing regimens might be effective in a subset of pediatric patients, especially those with predominantly contrast-enhancing disease.

Renal blood flow measurement with contrast-enhanced harmonic ultrasonography: evaluation of dopamine-induced changes in renal cortical perfusion in humans.

PubMed

Kishimoto, N; Mori, Y; Nishiue, T; Shibasaki, Y; Iba, O; Nose, A; Uchiyama-Tanaka, Y; Masaki, H; Matsubara, H; Iwasaka, T

2003-06-01

An accessible non-invasive method for evaluating renal regional blood flow in real time is highly desirable in the clinical setting. Recent progress in ultrasonography with microbubble contrast has allowed quantification of regional blood flow in animal models. Goal ofthis study was to establish a convenient contrast--enhanced harmonic ultrasonography (CEHU) method for evaluating renal cortical blood flow in humans. We carried out intermittent second harmonic imaging in 9 healthy volunteers. Pulse interval was progressively decreased from 4 s - 0.2 s during continuous venous infusion of the microbubble contrast agent. Pulse interval versus CEHU-derived acoustic intensity plots provided microbubble velocity (MV) and fractional vascular volume (FVV) during renal cortical perfusion in humans. Low-dose dopamine infusion (2 microg/min/kg) resulted in a significant increase in MV which correlated well with the increase in total renal blood flow (RBF) determined by a conventional study of p-aminohippurate clearance (C(PAH)) (r = 0.956, p < 0.0001). Although FVV was not significantly increased, alterations in CEHU-derived renal cortical blood flow calculated by the products of MV and FVV were also correlated with alterations in total RBF (r = 0.969, p < 0.0001). Thus, low-dose dopamine infusion increases renal cortical blood flow observed in CEHU, mainly by increasing MV. The present study shows that renal cortical blood flow in humans can be measured non-invasively by CEHU and that CEHU can be used for quantitatively evaluating changes induced by a therapeutic agent such as dopamine in flow velocity and in FVV.

Erythrocyte membrane fluidity and indices of plasmatic oxidative damage after acute physical exercise in humans.

PubMed

Berzosa, C; Gómez-Trullén, E M; Piedrafita, E; Cebrián, I; Martínez-Ballarín, E; Miana-Mena, F J; Fuentes-Broto, L; García, J J

2011-06-01

Optimal levels of membrane fluidity are essential for numerous cell functions including cell growth, solute transport and signal transduction. Since exercise enhances free radical production, our aim was to evaluate in healthy male subjects the effects of an acute bout of maximal and submaximal exercise on the erythrocyte membrane fluidity and its possible relation to the oxidative damage overproduction due to exercise. Subjects (n = 34) performed three cycloergometric tests: a continuous progressive exercise, a strenuous exercise until exhaustion and an acute bout of exercise at an intensity corresponding to 70% of maximal work capacity for 30 min. Venous blood samples were collected before and immediately after these exercises. Erythrocyte membrane fluidity was assessed by fluorescence spectroscopy. Plasma malondialdehyde (MDA) and 4-hydroxyalkenals (4-HDA) concentrations and carbonyl content of plasmatic proteins were used as an index of lipid and protein oxidation, respectively. Exercise produced a dramatic drop in the erythrocyte membrane fluidity as compared to resting time, but this was not accompanied by significant changes in the plasmatic MDA and 4-HDA concentrations. The highest erythrocyte membrane rigidity was detected immediately after strenuous exercise until exhaustion was performed. Protein carbonyl levels were higher after exhaustive exercises than at rest. Continuous progressive and strenuous exercises until exhaustion, but not submaximal workload, resulted in a significant enhanced accumulation of carbonylated proteins in the plasma. These findings are consistent with the idea that exercise exaggerates oxidative damage, which may contribute, at least partially, to explain the rigidity in the membrane of the erythrocytes due to acute exercise.

Ethanol Extract of Mylabris phalerata Inhibits M2 Polarization Induced by Recombinant IL-4 and IL-13 in Murine Macrophages

PubMed Central

Chung, Hwan-Suck; Lee, Bong-Seon

2017-01-01

Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment. In this line, we screened oriental medicines to find M1 polarizing medicines in M2-polarized macrophages. Among approximately 400 types of oriental medicine, the ethanol extract of M. phalerata (EMP) was the most proficient in increasing TNF-α secretion in M2-polarized macrophages and TAM. Although EMP enhanced the levels of an M1 cytokine (TNF-α) and a marker (CD86), it significantly reduced the levels of an M2 marker (arginase-1) in M2-polarized macrophages. In addition, EMP-treated macrophages increased the levels of M1 markers (Inos and Tnf-α) and reduced those of the enhanced M2 markers (Fizz-1, Ym-1, and arginase-1). EMP-treated macrophages significantly reduced Lewis lung carcinoma cell migration in a transwell migration assay and inhibited EL4-luc2 lymphoma proliferation. In our mechanism study, EMP was found to inhibit STAT3 phosphorylation in M2-polarized macrophages. These results suggest that EMP is effective in treating TAM-mediated tumor progression and metastasis. PMID:28811825

Crew/Automation Interaction in Space Transportation Systems: Lessons Learned from the Glass Cockpit

NASA Technical Reports Server (NTRS)

Rudisill, Marianne

2000-01-01

The progressive integration of automation technologies in commercial transport aircraft flight decks - the 'glass cockpit' - has had a major, and generally positive, impact on flight crew operations. Flight deck automation has provided significant benefits, such as economic efficiency, increased precision and safety, and enhanced functionality within the crew interface. These enhancements, however, may have been accrued at a price, such as complexity added to crew/automation interaction that has been implicated in a number of aircraft incidents and accidents. This report briefly describes 'glass cockpit' evolution. Some relevant aircraft accidents and incidents are described, followed by a more detailed description of human/automation issues and problems (e.g., crew error, monitoring, modes, command authority, crew coordination, workload, and training). This paper concludes with example principles and guidelines for considering 'glass cockpit' human/automation integration within space transportation systems.

On the stabilizing role of species diffusion in chemical enhanced oil recovery

NASA Astrophysics Data System (ADS)

Daripa, Prabir; Gin, Craig

2015-11-01

In this talk, the speaker will discuss a problem on the stability analysis related to the effect of species diffusion on stabilization of fingering in a Hele-Shaw model of chemical enhanced oil recovery. The formulation of the problem is motivated by a specific design principle of the immiscible interfaces in the hope that this will lead to significant stabilization of interfacial instabilities, there by improving oil recovery in the context of porous media flow. Testing the merits of this hypothesis poses some challenges which will be discussed along with some numerical results based on current formulation of this problem. Several open problems in this context will be discussed. This work is currently under progress. Supported by the grant NPRP 08-777-1-141 from the Qatar National Research Fund (a member of The Qatar Foundation).

SDDOT'S enhanced pavement management system : visual distress survey manual [2017

DOT National Transportation Integrated Search

2017-05-11

In 1993, the South Dakota Department of Transportation initiated the Research Project SD93-14, Enhancement of South Dakotas Pavement Management System. As the Research Project progressed, it was determined that to better evaluate the condition of ...

Functional imaging of the angiogenic switch in a transgenic mouse model of human breast cancer by dynamic contrast enhanced magnetic resonance imaging.

PubMed

Consolino, Lorena; Longo, Dario Livio; Dastrù, Walter; Cutrin, Juan Carlos; Dettori, Daniela; Lanzardo, Stefania; Oliviero, Salvatore; Cavallo, Federica; Aime, Silvio

2016-07-15

Tumour progression depends on several sequential events that include the microenvironment remodelling processes and the switch to the angiogenic phenotype, leading to new blood vessels recruitment. Non-invasive imaging techniques allow the monitoring of functional alterations in tumour vascularity and cellularity. The aim of this work was to detect functional changes in vascularisation and cellularity through Dynamic Contrast Enhanced (DCE) and Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) modalities during breast cancer initiation and progression of a transgenic mouse model (BALB-neuT mice). Histological examination showed that BALB-neuT mammary glands undergo a slow neoplastic progression from simple hyperplasia to invasive carcinoma, still preserving normal parts of mammary glands. DCE-MRI results highlighted marked functional changes in terms of vessel permeability (K(trans) , volume transfer constant) and vascularisation (vp , vascular volume fraction) in BALB-neuT hyperplastic mammary glands if compared to BALB/c ones. When breast tissue progressed from simple to atypical hyperplasia, a strong increase in DCE-MRI biomarkers was observed in BALB-neuT in comparison to BALB/c mice (K(trans)  = 5.3 ± 0.7E-4 and 3.1 ± 0.5E-4; vp  = 7.4 ± 0.8E-2 and 4.7 ± 0.6E-2 for BALB-neuT and BALB/c, respectively) that remained constant during the successive steps of the neoplastic transformation. Consistent with DCE-MRI observations, microvessel counting revealed a significant increase in tumour vessels. Our study showed that DCE-MRI estimates can accurately detect the angiogenic switch at early step of breast cancer carcinogenesis. These results support the view that this imaging approach is an excellent tool to characterize microvasculature changes, despite only small portions of the mammary glands developed neoplastic lesions in a transgenic mouse model. © 2016 UICC.

Regulation of a TGF-β1-CD147 self-sustaining network in the differentiation plasticity of hepatocellular carcinoma cells.

PubMed

Wu, J; Lu, M; Li, Y; Shang, Y-K; Wang, S-J; Meng, Y; Wang, Z; Li, Z-S; Chen, H; Chen, Z-N; Bian, H

2016-10-20

Cellular plasticity has an important role in the progression of hepatocellular carcinoma (HCC). In this study, the involvement of a TGF-β1-CD147 self-sustaining network in the regulation of the dedifferentiation progress was fully explored in HCC cell lines, hepatocyte-specific basigin/CD147-knockout mice and human HCC tissues. We demonstrated that TGF-β1 stimulation upregulated CD147 expression and mediated the dedifferentiation of HCC cells, whereas all-trans-retinoic acid induced the downregulation of CD147 and promoted differentiation in HCC cells. Overexpression of CD147 induced the dedifferentiation and enhanced the malignancy of HCC cells, and increased the transcriptional expression of TGF-β1 by activating β-catenin. CD147-induced matrix metalloproteinase (MMP) production activated pro-TGF-β1. The activated TGF-β1 signaling subsequently repressed the HNF4α expression via Smad-Snail1 signaling and enhanced the dedifferentiation progress. Hepatocyte-specific basigin/CD147-knockout mice decreased the susceptibility to N-nitrosodiethylamine-induced tumorigenesis by suppressing TGF-β1-CD147 signaling and inhibiting dedifferentiation in hepatocytes during tumor progression. CD147 was positively correlated with TGF-β1 and negatively correlated with HNF4α in human HCC tissues. Positive CD147 staining and lower HNF4α levels in tumor tissues were significantly associated with poor survival of patients with HCC. The overexpression of HNF4α and Smad7 and the deletion of CD147 by lentiviral vectors jointly reprogrammed the expression profile of hepatocyte markers and attenuated malignant properties including proliferation, cell survival and tumor growth of HCC cells. Our results highlight the important role of the TGF-β1-CD147 self-sustaining network in driving HCC development by regulating differentiation plasticity, which provides a strong basis for further investigations of the differentiation therapy of HCC targeting TGF-β1 and CD147.

Overexpression of EMMPRIN Isoform 2 Is Associated with Head and Neck Cancer Metastasis

PubMed Central

Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

2014-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2), urokinase-type plasminogen activator(uPA) and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel mechanism underlying EMMPRIN-2 enhanced tumor progression in head and neck cancer. PMID:24705283

Overexpression of EMMPRIN isoform 2 is associated with head and neck cancer metastasis.

PubMed

Huang, Zhiquan; Tan, Ning; Guo, Weijie; Wang, Lili; Li, Haigang; Zhang, Tianyu; Liu, Xiaojia; Xu, Qin; Li, Jinsong; Guo, Zhongmin

2014-01-01

Extracellular matrix metalloproteinase inducer (EMMPRIN), a plasma membrane protein of the immunoglobulin (Ig) superfamily, has been reported to promote cancer cell invasion and metastasis in several human malignancies. However, the roles of the different EMMPRIN isoforms and their associated mechanisms in head and neck cancer progression remain unknown. Using quantitative real-time PCR, we found that EMMPRIN isoform 2 (EMMPRIN-2) was the only isoform that was overexpressed in both head and neck cancer tissues and cell lines and that it was associated with head and neck cancer metastasis. To determine the effects of EMMPRIN-2 on head and neck cancer progression, we transfected head and neck cancer cells with an EMMPRIN-2 expression vector and EMMPRIN-2 siRNA to exogenously modulate EMMPRIN-2 expression and examined the functional importance of EMMPRIN-2 in head and neck cancer invasion and metastasis. We found that EMMPRIN-2 promoted head and neck cancer cell invasion, migration, and adhesion in vitro and increased lung metastasis in vivo. Mechanistic studies revealed that EMMPRIN-2 overexpression promoted the secretion of extracellular signaling molecules, including matrix metalloproteinases-2(MMP-2), urokinase-type plasminogen activator(uPA) and Cathepsin B, in head and neck cancer cells. While MMP-2 and uPA have been demonstrated to be important mediators of EMMPRIN signaling, the role of Cathepsin B in EMMPRIN-mediated molecular cascades and tumorigenesis has not been established. We found that EMMPRIN-2 overexpression and Cathepsin B down-regulation significantly inhibited the invasion, migration and adhesion of Tca8133 cells, suggesting that Cathepsin B is required for EMMPRIN-2 enhanced cell migration and invasion in head and neck cancer. The results of our study demonstrate the important role of EMMPRIN-2 in head and neck cancer progression for the first time and reveal that increased extracellular secretion of Cathepsin B may be a novel mechanism underlying EMMPRIN-2 enhanced tumor progression in head and neck cancer.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma.

PubMed

Porcu, Cristiana; Antonucci, Laura; Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-02-06

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies.

Radiation necrosis presenting as pseudoprogression (PsP) during alectinib treatment of previously radiated brain metastases in ALK-positive NSCLC: Implications for disease assessment and management.

PubMed

Ou, Sai-Hong Ignatius; Klempner, Samuel J; Azada, Michele C; Rausei-Mills, Veronica; Duma, Christopher

2015-06-01

Radiation necrosis presenting as pseudoprogression (PsP) is relatively common after radiation and temozolomide (TMZ) treatment in glioblastoma multiforme (GBM), especially among patients with GBM that harbors intrinsic increased responsiveness to TMZ (methylated O6-methylguanine-DNA methyltransferase [MGMT] promoter). Alectinib is a second generation ALK inhibitor that has significant CNS activity against brain metastases in anaplastic lymphoma kinase (ALK)-rearranged (ALK+) non-small cell lung cancer (NSCLC) patients. We report 2 ALK+ NSCLC patients who met RECIST criteria for progressive disease by central radiologic review due to increased in size from increased contrast enhancement in previously stereotactically radiated brain metastases with ongoing extra-cranial response to alectinib. In both patients alectinib was started within 4 months of completing stereotactic radiosurgery (SRS). The enlarging lesions in both patients were resected and found to have undergone extensive necrosis with no residual tumor pathologically. PsP was incorrectly classified as progressive disease even by central independent imaging review. Treatment-related necrosis of previously SRS-treated brain metastasis during alectinib treatment can present as PsP. It may be impossible to distinguish PsP from true disease progression without a pathologic examination from resected sample. High degree of clinical suspicion, close monitoring and more sensitive imaging modalities may be needed to distinguish PsP versus progression in radiated brain lesions during alectinib treatment especially if there is no progression extra-cranially. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Immunopathological Changes in the Brain of Immunosuppressed Mice Experimentally Infected with Toxocara canis

PubMed Central

Eid, Mohamed M.; El-Kowrany, Samy I.; Othman, Ahmad A.; Gendy, Dina I. El; Saied, Eman M.

2015-01-01

Toxocariasis is a soil-transmitted helminthozoonosis due to infection of humans by larvae of Toxocara canis. The disease could produce cognitive and behavioral disturbances especially in children. Meanwhile, in our modern era, the incidence of immunosuppression has been progressively increasing due to increased incidence of malignancy as well as increased use of immunosuppressive agents. The present study aimed at comparing some of the pathological and immunological alterations in the brain of normal and immunosuppressed mice experimentally infected with T. canis. Therefore, 180 Swiss albino mice were divided into 4 groups including normal (control) group, immunocompetent T. canis-infected group, immunosuppressed group (control), and immunosuppressed infected group. Infected mice were subjected to larval counts in the brain, and the brains from all mice were assessed for histopathological changes, astrogliosis, and IL-5 mRNA expression levels in brain tissues. The results showed that under immunosuppression, there were significant increase in brain larval counts, significant enhancement of reactive gliosis, and significant reduction in IL-5 mRNA expression. All these changes were maximal in the chronic stage of infection. In conclusion, the immunopathological alterations in the brains of infected animals were progressive over time, and were exaggerated under the effect of immunosuppression as did the intensity of cerebral infection. PMID:25748709

The Assessment of the Impact of REU Programs on Student Classroom Performance

NASA Astrophysics Data System (ADS)

Hughes, Chris

2009-03-01

Supporters of undergraduate research claim that the research experience enhances the success of students in their classes and promotes their progress toward completing a science major. Since there are many other variables that can influence a student's progress through a curriculum, it is frequently difficult to compare students from undergraduate research programs with a suitable control group. At James Madison University, a significant number of chemistry and physics majors participate in summer REU programs on campus. However, since JMU is among the top 10% of undergraduate institutions in the US in undergraduate physics enrollment, there are also a significant number who choose not to stay on campus for summer research. Using several years worth of data, we have determined the change in the GPAs of REU students (N=75) from the semester before the REU to the semester after the REU and compared these with the students who did not participate in summer research (N=663). We have found that the REU students' average GPA increased by a statistically significant amount while the non-REU students' average GPA was unchanged to within a standard deviation. We will also discuss other assessment methods used at JMU and some of the limitations in the interpretation of this study.

Non-DBS DNA Repair Genes Regulate Radiation-induced Cytogenetic Damage Repair and Cell Cycle Progression

NASA Technical Reports Server (NTRS)

Zhang, Ye; Rohde, Larry H.; Emami, Kamal; Casey, Rachael; Wu, Honglu

2008-01-01

Changes of gene expression profile are one of the most important biological responses in living cells after ionizing radiation (IR) exposure. Although some studies have shown that genes up-regulated by IR may play important roles in DNA damage repair, the relationship between the regulation of gene expression by IR, particularly genes not known for their roles in DSB repair, and its impact on cytogenetic responses has not been systematically studied. In the present study, the expression of 25 genes selected on the basis of their transcriptional changes in response to IR was individually knocked down by transfection with small interfering RNA in human fibroblast cells. The purpose of this study is to identify new roles of these selected genes on regulating DSB repair and cell cycle progression , as measured in the micronuclei formation and chromosome aberration. In response to IR, the formation of MN was significantly increased by suppressed expression of 5 genes: Ku70 in the DSB repair pathway, XPA in the NER pathway, RPA1 in the MMR pathway, and RAD17 and RBBP8 in cell cycle control. Knocked-down expression of 4 genes (MRE11A, RAD51 in the DSB pathway, SESN1, and SUMO1) significantly inhibited cell cycle progression, possibly because of severe impairment of DNA damage repair. Furthermore, loss of XPA, P21, or MLH1 expression resulted in both significantly enhanced cell cycle progression and increased yields of chromosome aberrations, indicating that these gene products modulate both cell cycle control and DNA damage repair. Most of the 11 genes that affected cytogenetic responses are not known to have clear roles influencing DBS repair. Nine of these 11 genes were up-regulated in cells exposed to gamma radiation, suggesting that genes transcriptionally modulated by IR were critical to regulate the biological consequences after IR.

Cumulative Significance of Hyporheic Exchange and Biogeochemical Processing in River Networks

NASA Astrophysics Data System (ADS)

Harvey, J. W.; Gomez-Velez, J. D.

2014-12-01

Biogeochemical reactions in rivers that decrease excessive loads of nutrients, metals, organic compounds, etc. are enhanced by hydrologic interactions with microbially and geochemically active sediments of the hyporheic zone. The significance of reactions in individual hyporheic flow paths has been shown to be controlled by the contact time between river water and sediment and the intrinsic reaction rate in the sediment. However, little is known about how the cumulative effects of hyporheic processing in large river basins. We used the river network model NEXSS (Gomez-Velez and Harvey, submitted) to simulate hyporheic exchange through synthetic river networks based on the best available models of network topology, hydraulic geometry and scaling of geomorphic features, grain size, hydraulic conductivity, and intrinsic reaction rates of nutrients and metals in river sediment. The dimensionless reaction significance factor, RSF (Harvey et al., 2013) was used to quantify the cumulative removal fraction of a reactive solute by hyporheic processing. SF scales reaction progress in a single pass through the hyporheic zone with the proportion of stream discharge passing through the hyporheic zone for a specified distance. Reaction progress is optimal where the intrinsic reaction timescale in sediment matches the residence time of hyporheic flow and is less efficient in longer residence time hyporheic flow as a result of the decreasing proportion of river flow that is processed by longer residence time hyporheic flow paths. In contrast, higher fluxes through short residence time hyporheic flow paths may be inefficient because of the repeated surface-subsurface exchanges required to complete the reaction. Using NEXSS we found that reaction efficiency may be high in both small streams and large rivers, although for different reasons. In small streams reaction progress generally is dominated by faster pathways of vertical exchange beneath submerged bedforms. Slower exchange beneath meandering river banks mainly has importance only in large rivers. For solutes entering networks in proportion to water inputs it is the lower order streams that tend to dominate cumulative reaction progress.

The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats.

PubMed

Hamlyn, Eugene; Brand, Linda; Shahid, Mohammed; Harvey, Brian H

2009-10-01

Ampakines have shown beneficial effects on cognition in selected animal models of learning. However, their ability to modify long-term spatial memory tasks has not been studied yet. This would lend credence to their possible value in treating disorders of cognition. We evaluated the actions of subchronic Org 26576 administration on spatial reference memory performance in the 5-day Morris water maze task in male Sprague-Dawley rats, at doses of 1, 3 and 10 mg/kg twice daily through intraperitoneal injection over 12 days. Org 26576 exerted a dose and time-dependent effect on spatial learning, with dosages of 3 and 10 mg/kg significantly enhancing acquisition on day 1. Globally, escape latency decreased significantly as the training days progressed in the saline and Org 26576-treated groups, indicating that significant and equal learning had taken place over the learning period. However, at the end of the learning period, all doses of Org 26576 significantly improved spatial memory storage/retrieval without confounding effects in the cued version of the task. Org 26576 offers early phase spatial memory benefits in rats, but particularly enhances search accuracy during reference memory retrieval. These results support its possible utility in treating disorders characterized by deficits in cognitive performance.

Dryland climate change: Recent progress and challenges

NASA Astrophysics Data System (ADS)

Huang, J.; Li, Y.; Fu, C.; Chen, F.; Fu, Q.; Dai, A.; Shinoda, M.; Ma, Z.; Guo, W.; Li, Z.; Zhang, L.; Liu, Y.; Yu, H.; He, Y.; Xie, Y.; Guan, X.; Ji, M.; Lin, L.; Wang, S.; Yan, H.; Wang, G.

2017-09-01

Drylands are home to more than 38% of the world's population and are one of the most sensitive areas to climate change and human activities. This review describes recent progress in dryland climate change research. Recent findings indicate that the long-term trend of the aridity index (AI) is mainly attributable to increased greenhouse gas emissions, while anthropogenic aerosols exert small effects but alter its attributions. Atmosphere-land interactions determine the intensity of regional response. The largest warming during the last 100 years was observed over drylands and accounted for more than half of the continental warming. The global pattern and interdecadal variability of aridity changes are modulated by oceanic oscillations. The different phases of those oceanic oscillations induce significant changes in land-sea and north-south thermal contrasts, which affect the intensity of the westerlies and planetary waves and the blocking frequency, thereby altering global changes in temperature and precipitation. During 1948-2008, the drylands in the Americas became wetter due to enhanced westerlies, whereas the drylands in the Eastern Hemisphere became drier because of the weakened East Asian summer monsoon. Drylands as defined by the AI have expanded over the last 60 years and are projected to expand in the 21st century. The largest expansion of drylands has occurred in semiarid regions since the early 1960s. Dryland expansion will lead to reduced carbon sequestration and enhanced regional warming. The increasing aridity, enhanced warming, and rapidly growing population will exacerbate the risk of land degradation and desertification in the near future in developing countries.

EMPOWERING ADULT STEM CELLS FOR MYOCARDIAL REGENERATION

PubMed Central

Mohsin, Sadia; Siddiqi, Sailay; Collins, Brett; Sussman, Mark A.

2012-01-01

Treatment strategies for heart failure remain a high priority for ongoing research due to the profound unmet need in clinical disease coupled with lack of significant translational progress. The underlying issue is the same whether the cause is acute damage, chronic stress from disease, or aging: progressive loss of functional cardiomyocytes and diminished hemodynamic output. To stave off cardiomyocyte losses, a number of strategic approaches have been embraced in recent years involving both molecular and cellular approaches to augment myocardial structure and performance. Resultant excitement surrounding regenerative medicine in the heart has been tempered by realizations that reparative processes in the heart are insufficient to restore damaged myocardium to normal functional capacity and that cellular cardiomyoplasty is hampered by poor survival, proliferation, engraftment and differentiation of the donated population. To overcome these limitations, a combination of molecular and cellular approaches needs to be adopted involving use of genetic engineering to enhance resistance to cell death and increase regenerative capacity. This review will highlight biological properties of approached to potentiate stem cell-mediated regeneration to promote enhanced myocardial regeneration, persistence of donated cells, and long lasting tissue repair. Optimizing cell delivery and harnessing the power of survival signaling cascades for ex vivo genetic modification of stem cells prior to reintroduction into the patient will be critical to enhance the efficacy of cellular cardiomyoplasty. Once this goal is achieved, then cell-based therapy has great promise for treatment of heart failure to combat the loss of cardiac structure and function associated with acute damage, chronic disease or aging. PMID:22158649

Recent Progress Towards Quantum Dot Solar Cells with Enhanced Optical Absorption.

PubMed

Zheng, Zerui; Ji, Haining; Yu, Peng; Wang, Zhiming

2016-12-01

Quantum dot solar cells, as a promising candidate for the next generation solar cell technology, have received tremendous attention in the last 10 years. Some recent developments in epitaxy growth and device structures have opened up new avenues for practical quantum dot solar cells. Unfortunately, the performance of quantum dot solar cells is often plagued by marginal photon absorption. In this review, we focus on the recent progress made in enhancing optical absorption in quantum dot solar cells, including optimization of quantum dot growth, improving the solar cells structure, and engineering light trapping techniques.

Nutritionally enhanced food crops; progress and perspectives.

PubMed

Hefferon, Kathleen L

2015-02-11

Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world's poor are under development as well as new varieties of crops which have the ability to combat chronic disease. This review discusses the improvement of the nutritional status of crops to make a positive impact on global human health. Several examples of nutritionally enhanced crops which have been developed using biotechnological approaches will be discussed. These range from biofortified crops to crops with novel abilities to fight disease. The review concludes with a discussion of hurdles faced with respect to public perception, as well as directions of future research and development for nutritionally enhanced food crops.

Mindfulness and Loving-Kindness Meditation.

PubMed

Aspy, Denholm J; Proeve, Michael

2017-02-01

An experiment involving 115 undergraduate students (74.8% females; mean age = 20.5 years, SD = 4.3) was conducted to explore effects of meditation on social connectedness, nature connectedness, and affect. Participants listened to one of three brief guided meditation Mp3 recordings via the internet, which involved mindfulness meditation (MM), loving-kindness meditation (LKM), or progressive muscle relaxation (active control group). Participants in the MM and LKM groups reported greater social and nature connectedness at post-test than those in the control group. There were no significant differences in connectedness between the MM and LKM groups, suggesting they are both effective for enhancing connectedness. There were no significant changes in negative or positive affect at post-test due to the interventions. Recommendations for future research are provided.

Environmental assessment for the Processing and Environmental Technology Laboratory (PETL)

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-09-01

The U.S. Department of Energy (DOE) has prepared an environmental assessment (EA) on the proposed Processing and Environmental Technology Laboratory (PETC) at Sandia National Laboratories/New Mexico (SNL/NM). This facility is needed to integrate, consolidate, and enhance the materials science and materials process research and development (R&D) currently in progress at SNL/NM. Based on the analyses in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, an environmental impact statement is not required, andmore » DOE is issuing this Finding of No Significant Impact (FONSI).« less

Progress in linear optics, non-linear optics and surface alignment of liquid crystals

NASA Astrophysics Data System (ADS)

Ong, H. L.; Meyer, R. B.; Hurd, A. J.; Karn, A. J.; Arakelian, S. M.; Shen, Y. R.; Sanda, P. N.; Dove, D. B.; Jansen, S. A.; Hoffmann, R.

We first discuss the progress in linear optics, in particular, the formulation and application of geometrical-optics approximation and its generalization. We then discuss the progress in non-linear optics, in particular, the enhancement of a first-order Freedericksz transition and intrinsic optical bistability in homeotropic and parallel oriented nematic liquid crystal cells. Finally, we discuss the liquid crystal alignment and surface effects on field-induced Freedericksz transition.

Relaxation-Induced Anxiety: Paradoxical Anxiety Enhancement Due to Relaxation Training.

ERIC Educational Resources Information Center

Heide, Frederick J.; Borkovec, T. D.

1983-01-01

Documented relaxation-induced anxiety in 14 subjects suffering from tension who were given training in progressive relaxation and mantra meditation. Four of the subjects displayed clinical evidence of an anxiety reaction during a preliminary practice period. Progressive relaxation produced less evidence of relaxation-induced anxiety. (Author/JAC)

Evaluating Youth Development Programs: Progress and Promise

ERIC Educational Resources Information Center

Roth, Jodie L.; Brooks-Gunn, Jeanne

2016-01-01

Advances in theories of adolescent development and positive youth development have greatly increased our understanding of how programs and practices with adolescents can impede or enhance their development. In this article the authors reflect on the progress in research on youth development programs in the last two decades, since possibly the…

Progress in Scientific and Technical Communications, 1968 Annual Report.

ERIC Educational Resources Information Center

Federal Council for Science and Technology, Washington, DC. Committee on Scientific and Technical Information.

This sixth annual report describes progress achieved by the Federal Government in improving the communication of scientific and technical information to support and enhance national science and technology. Included in the report are details regarding the scientific and technical activities of individual Federal Agencies, such as the Atomic Energy…

Integration of Culturally Relevant Pedagogy into the Science Learning Progression Framework

ERIC Educational Resources Information Center

Bernardo, Cyntra

2017-01-01

This study integrated elements of culturally relevant pedagogy into a science learning progression framework, with the goal of enhancing teachers' cultural knowledge and thereby creating better teaching practices in an urban public high school science classroom. The study was conducted using teachers, an administrator, a science coach, and…

Increased phospho-AKT is associated with loss of the androgen receptor during the progression of N-methyl-N-nitrosourea-induced prostate carcinogenesis in rats.

PubMed

Liao, Zhiming; Wang, Shihua; Boileau, Thomas W-M; Erdman, John W; Clinton, Steven K

2005-07-01

Characterization of molecular events during N-methyl-N-nitrosourea (MNU)-induced rat prostate carcinogenesis enhances the utility of this model for the preclinical assessment of preventive strategies. Androgen independence is typical of advanced human prostate cancer and may occur through multiple mechanisms including the loss of androgen receptor (AR) expression and the activation of alternative signaling pathways. We examined the interrelationships between AR and p-AKT expression by immunohistochemical staining during MNU-androgen-induced prostate carcinogenesis in male Wistar-Unilever rats. Histone nuclear staining and image analysis was employed to assess parallel changes in chromatin and nuclear structure. The percentage of AR positive nuclei decreased (P < 0.01) as carcinogenesis progressed: hyperplasia (92%), atypical hyperplasia (92%), well-differentiated adenocarcinoma (57%), moderately-differentiated adenocarcinoma (19%), and poorly-differentiated adenocarcinoma (10%). Conversely, p-AKT staining increased significantly during carcinogenesis. Sparse staining was observed in normal tissues (0.2% of epithelial area) and hyperplastic lesions (0.1%), while expression increased significantly (P < 0.001) in atypical hyperplasia (7.6%), well-differentiated adenocarcinoma (16.7%), moderately-differentiated adenocarcinoma (19.6%), and poorly-differentiated adenocarcinoma (17.4%). In parallel, nuclear morphometry revealed increased nuclear size, greater irregularity, and lower DNA compactness as cancers became more poorly differentiated. In the MNU model, the progressive evolution of dominant tumor cell populations showing an increase in p-AKT in parallel with a decline in AR staining suggests that activation of AKT signaling may be one of several mechanisms contributing to androgen insensitivity during prostate cancer progression. Our observations mimic findings suggested by human studies and support the relevance of the MNU model in preclinical studies of preventive strategies. (c) 2005 Wiley-Liss, Inc.

Change of synovial vascularity in a single finger joint assessed by power doppler sonography correlated with radiographic change in rheumatoid arthritis: comparative study of a novel quantitative score with a semiquantitative score.

PubMed

Fukae, Jun; Kon, Yujiro; Henmi, Mihoko; Sakamoto, Fumihiko; Narita, Akihiro; Shimizu, Masato; Tanimura, Kazuhide; Matsuhashi, Megumi; Kamishima, Tamotsu; Atsumi, Tatsuya; Koike, Takao

2010-05-01

To investigate the relationship between synovial vascularity assessed by quantitative power Doppler sonography (PDS) and progression of structural bone damage in a single finger joint in patients with rheumatoid arthritis (RA). We studied 190 metacarpophalangeal (MCP) joints and 190 proximal interphalangeal (PIP) joints of 19 patients with active RA who had initial treatment with disease-modifying antirheumatic drugs (DMARDs). Patients were examined by clinical and laboratory assessments throughout the study. Hand and foot radiography was performed at baseline and the twentieth week. Magnetic resonance imaging (MRI) was performed at baseline. PDS was performed at baseline and the eighth week. Synovial vascularity was evaluated according to both quantitative and semiquantitative methods. Quantitative PDS was significantly correlated with the enhancement rate of MRI in each single finger joint. Comparing quantitative synovial vascularity and radiographic change in single MCP or PIP joints, the level of vascularity at baseline showed a significant positive correlation with radiographic progression at the twentieth week. The change of vascularity in response to DMARDs, defined as the percentage change in vascularity by the eighth week from baseline, was inversely correlated with radiographic progression in each MCP joint. The quantitative PDS method was more useful than the semiquantitative method for the evaluation of synovial vascularity in a single finger joint. The change of synovial vascularity in a single finger joint determined by quantitative PDS could numerically predict its radiographic progression. Using vascularity as a guide to consider a therapeutic approach would have benefits for patients with active RA.

Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

PubMed Central

Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

2015-01-01

Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

A reconnaissance space sensing investigation of crustal structure for a strip from the eastern Sierra Nevada to the Colorado Plateau

NASA Technical Reports Server (NTRS)

Bechtold, I. C. (Principal Investigator); Liggett, M. L.; Childs, J. F.

1973-01-01

There are no author-identified significant results in this report. Research progress in applications of ERTS-1 MSS imagery in study of Basin-Range tectonics is summarized. Field reconnaissance of ERTS-1 image anomalies has resulted in recognition of previously unreported fault zones and regional structural control of volcanic and plutonic activity. NIMBUS, Apollo 9, X-15, U-2, and SLAR imagery are discussed with specific applications, and methods of image enhancement and analysis employed in the research are summarized. Areas studied and methods employed in geologic field work are outlined.

A reconnaissance space sensing investigation of crustal structure for a strip from the eastern Sierra Nevada to the Colorado Plateau

NASA Technical Reports Server (NTRS)

Liggett, M. A.; Childs, J. F.

1973-01-01

The author has identified the following significant results. Research progress in applications of ERTS-1 MSS imagery to study of Basin-Range tectonics is summarized. Field reconnaissance of ERTS-1 image anomalies has resulted in recognition of previously unreported fault zones and regional structural control of volcanic and plutonic activity. Nimbus, Apollo 9, X-15, U-2, and SIAR imagery are discussed with specific applications, and methods of image enhancement and analysis employed in the research are summarized. Field areas studied and methods employed in geologic field work are outlined.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neft, R.E.; Tierney, L.A.; Belinsky, S.A.

Molecular and immunological techniques may enhance the usefulness of sputum cytology as a screening tool for lung cancer. These techniques may also be useful in detecting and following the early progression of disease from metaplasia to dysplasia, carcinoma in situ, and finally to invasive carcinoma. Longitudinal information on the evolution of these malignant changes in the respiratory epithelium can be gained by prospective study of populations at high risk for lung cancer. This work is significant because double-labeling of cells in sputum with p53 and cytokeratin antibodies facilitates rapid screening of p53 positive neoplastic and preneoplastic lung cells by brightfieldmore » and fluorescence microscopy.« less

Magnetic resonance imaging findings in fatal primary cerebral infection due to Chaetomium strumarium.

PubMed

Aribandi, M; Bazan Iii, C; Rinaldi, M G

2005-04-01

This report describes MRI findings of a rare case of biopsy-proven fatal cerebral infection with Chaetomium strumarium in a 28-year-old man with a history of i.v. drug abuse. Magnetic resonance imaging revealed rapidly progressing lesions with irregular peripheral enhancement, possible central haemorrhage and significant mass effect. Only six cases of cerebral infection with Chaetomium have been reported in the English literature. This is the first report in the radiology literature describing the imaging findings. The previously reported cases of cerebral infection by the Chaetomium species are also reviewed.

Study of a programmable high speed processor for use on-board satellites

NASA Astrophysics Data System (ADS)

Degavre, J. Cl.; Okkes, R.; Gaillat, G.

The availability of VLSI programmable devices will significantly enhance satellite on-board data processing capabilities. A case study is presented which indicates that computation-intensive processing applications requiring the execution of 100 megainstructions/sec are within the CD power constraints of satellites. It is noted that the current progress in semicustom design technique development and in achievable gate array densities, together with the recent announcement of improved monochip processors, are encouraging the development of an on-board programmable processor architecture able to associate the devices that will appear in communication and military markets.

[The Aim and Scope of "Clinical Practice Guidelines for the Management of Kidney Disease in Cancer Survivors"].

PubMed

Horie, Shigeo

2017-03-01

Drug-induced nephron-toxicity hampers the effective cancer chemotherapy and impairs the quality of life of the patients. Now eGFR has substituted Ccr for the estimation of renal function. The concepts and clinical significance of CKD and AKI have been established. These progress of clinical nephrology can improve the management of cancer chemotherapy. Clinical practice guidelines for the management of kidney disease in cancer survivors supports health-related professional to practice based on the evidence, which will enhance the efficacy of the treatment and QOL of the cancer survivors.

Current Status of Tissue-Engineered Scaffolds for Rotator Cuff Repair.

PubMed

Chainani, Abby; Little, Dianne

2016-06-01

Rotator cuff tears continue to be at significant risk for re-tear or for failure to heal after surgical repair despite the use of a variety of surgical techniques and augmentation devices. Therefore, there is a need for functionalized scaffold strategies to provide sustained mechanical augmentation during the critical first 12-weeks following repair, and to enhance the healing potential of the repaired tendon and tendon-bone interface. Tissue engineered approaches that combine the use of scaffolds, cells, and bioactive molecules towards promising new solutions for rotator cuff repair are reviewed. The ideal scaffold should have adequate initial mechanical properties, be slowly degrading or non-degradable, have non-toxic degradation products, enhance cell growth, infiltration and differentiation, promote regeneration of the tendon-bone interface, be biocompatible and have excellent suture retention and handling properties. Scaffolds that closely match the inhomogeneity and non-linearity of the native rotator cuff may significantly advance the field. While substantial pre-clinical work remains to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical translation.

Current Status of Tissue-Engineered Scaffolds for Rotator Cuff Repair

PubMed Central

Chainani, Abby; Little, Dianne

2015-01-01

Rotator cuff tears continue to be at significant risk for re-tear or for failure to heal after surgical repair despite the use of a variety of surgical techniques and augmentation devices. Therefore, there is a need for functionalized scaffold strategies to provide sustained mechanical augmentation during the critical first 12-weeks following repair, and to enhance the healing potential of the repaired tendon and tendon-bone interface. Tissue engineered approaches that combine the use of scaffolds, cells, and bioactive molecules towards promising new solutions for rotator cuff repair are reviewed. The ideal scaffold should have adequate initial mechanical properties, be slowly degrading or non-degradable, have non-toxic degradation products, enhance cell growth, infiltration and differentiation, promote regeneration of the tendon-bone interface, be biocompatible and have excellent suture retention and handling properties. Scaffolds that closely match the inhomogeneity and non-linearity of the native rotator cuff may significantly advance the field. While substantial pre-clinical work remains to be done, continued progress in overcoming current tissue engineering challenges should allow for successful clinical translation. PMID:27346922

Suppression of RND3 activity by AES downregulation promotes cancer cell proliferation and invasion.

PubMed

Xia, Hongwei; Li, Mingxing; Chen, Liang; Leng, Weibing; Yuan, Dandan; Pang, Xiaohui; Chen, Liu; Li, Ronghui; Tang, Qiulin; Bi, Feng

2013-05-01

Amino-terminal enhancer of split (AES) is a member of the Groucho/TLE family. Although it has no DNA-binding site, AES can regulate transcriptional activity by interacting with transcriptional factors. Emerging evidence indicates that AES may play an important role in tumor metastasis, but the molecular mechanism is still poorly understood. In this study, we found that knockdown of AES by RNA interference (RNAi) downregulated RND3 expression at the mRNA and protein levels in MDA-MB-231 and HepG2, two cancer cell lines. Furthermore, luciferase assays showed that overexpression of AES significantly enhanced RND3 promoter activity. Moreover, inhibition of AES both in MDA-MB-231 and HepG2 cells by RNAi significantly promoted cell proliferation, cell cycle progression and invasion, consistent with the effects of RNAi-mediated RND3 knockdown in these cells. For the first time, data are presented showing that alteration of the malignant behavior of cancer cells by AES is related to RND3 regulation, and these findings also provide new insights into the mechanism of AES action in regulating tumor malignancy.

Macrophage PPARγ inhibits Gpr132 to mediate the anti-tumor effects of rosiglitazone

PubMed Central

Cheng, Wing Yin; Huynh, HoangDinh; Chen, Peiwen; Peña-Llopis, Samuel; Wan, Yihong

2016-01-01

Tumor-associated macrophage (TAM) significantly contributes to cancer progression. Human cancer is enhanced by PPARγ loss-of-function mutations, but inhibited by PPARγ agonists such as TZD diabetes drugs including rosiglitazone. However, it remains enigmatic whether and how macrophage contributes to PPARγ tumor-suppressive functions. Here we report that macrophage PPARγ deletion in mice not only exacerbates mammary tumor development but also impairs the anti-tumor effects of rosiglitazone. Mechanistically, we identify Gpr132 as a novel direct PPARγ target in macrophage whose expression is enhanced by PPARγ loss but repressed by PPARγ activation. Functionally, macrophage Gpr132 is pro-inflammatory and pro-tumor. Genetic Gpr132 deletion not only retards inflammation and cancer growth but also abrogates the anti-tumor effects of PPARγ and rosiglitazone. Pharmacological Gpr132 inhibition significantly impedes mammary tumor malignancy. These findings uncover macrophage PPARγ and Gpr132 as critical TAM modulators, new cancer therapeutic targets, and essential mediators of TZD anti-cancer effects. DOI: http://dx.doi.org/10.7554/eLife.18501.001 PMID:27692066

Effects of Irradiation on Albite's Chemical Durability.

PubMed

Hsiao, Yi-Hsuan; La Plante, Erika Callagon; Krishnan, N M Anoop; Le Pape, Yann; Neithalath, Narayanan; Bauchy, Mathieu; Sant, Gaurav

2017-10-19

Albite (NaAlSi 3 O 8 ), a framework silicate of the plagioclase feldspar family and a common constituent of felsic rocks, is often present in the siliceous mineral aggregates that compose concrete. When exposed to radiation (e.g., in the form of neutrons) in nuclear power plants, the crystal structure of albite can undergo significant alterations. These alterations may degrade its chemical durability. Indeed, careful examinations of Ar + -implanted albite carried out using Fourier transform infrared spectroscopy (FTIR) and molecular dynamics simulations show that albite's crystal structure, upon irradiation, undergoes progressive disordering, resulting in an expansion in its molar volume (i.e., a reduction of density) and a reduction in the connectivity of its atomic network. This loss of network connectivity (i.e., rigidity) results in an enhancement of the aqueous dissolution rate of albite-measured using vertical scanning interferometry (VSI) in alkaline environments-by a factor of 20. This enhancement in the dissolution rate (i.e., reduction in chemical durability) of albite following irradiation has significant impacts on the durability of felsic rocks and of concrete containing them upon their exposure to radiation in nuclear power plant (NPP) environments.

Practice-based learning and improvement: a dream that can become a reality.

PubMed

Manning, Phil R

2003-01-01

Systematically enhancing learning from experience (practice-based learning) dominates the teachings of Sir William Osler and adult learning theorists such as Eduard Lindeman, Malcolm Knowles, and Cyril Houle. Because of time constraints, most physicians have not implemented methods that systematically facilitate learning from day-to-day work, but improvements in information technology offer the promise of making systematic practice-based learning practical. At least four ingredients need to be incorporated to significantly enhance learning from experience: a database that makes it possible to study individual practices; methods for supplying short, quick answers to questions while seeing patients; a reminder system to avoid errors of omission; and the opportunity to discuss practice data with colleagues. Great progress has been made, but significant barriers still must be overcome before a majority of physicians will participate. In particular, methods of data collection must be simplified, the delivery of point-of-care information and reminders must become more automatic, and physicians must develop skills to make the discussion of practice data acceptable, stimulating, and not unduly punitive.

Why Environmental Education? It Is Critical to Maintaining Our Quality of Life.

ERIC Educational Resources Information Center

Browner, Carol M.

1995-01-01

Traces the progress of environmental education and discusses its role in enhancing the quality of life on our planet. Describes several initiatives aimed at deepening environmental awareness among all Americans and enhancing participation in solving environmental problems. (JRH)

IL-17 Plays a Role in Respiratory Syncytial Virus-induced Lung Inflammation and Emphysema in Elastase and LPS-injured Mice.

PubMed

Mebratu, Yohannes A; Tesfaigzi, Yohannes

2018-06-01

Respiratory syncytial virus (RSV) is associated with enhanced progression of chronic obstructive pulmonary disease (COPD) and COPD exacerbations. However, little is known about the role of IL-17 in RSV-induced lung injury. We first investigated the role of RSV infection in enhancing mucous cell hyperplasia (MCH) and airspace enlargement in the lungs of mice injured with elastase and LPS (E/LPS). Mice injured with E/LPS had an enhanced and prolonged neutrophilic response to RSV that was associated with decreased levels of type I IFN and increased levels of IL-17, IL-23, CXCL-1, granulocyte colony stimulating factor (GCSF), CXCL-5, and matrix metalloproteinase (MMP)-9. In addition, extent of MCH and mean weighted alveolar space were increased significantly in the lungs of E/LPS-injured mice infected with RSV compared with E/LPS-only or RSV-only controls. Interestingly, immunodepletion of IL-17 before viral infection diminished the RSV-driven MCH and airspace enlargement in the E/LPS-injured animals, suggesting that IL-17 may be a therapeutic target for MCH and airspace enlargement when enhanced by RSV infection.

Therapeutic and prophylactic utility of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing electroconvulsive therapy: a randomized controlled trial.

PubMed

Prakash, Jyoti; Kotwal, Atul; Prabhu, Hra

2006-09-01

Substantial progress has been made in identifying how the treatment parameters used in electroconvulsive therapy (ECT) impact its cognitive side effects. However, there is limited information regarding the role of memory enhancers in post-ECT cognitive disturbances. We evaluated the therapeutic and prophylactic efficacy of the memory-enhancing drug donepezil hydrochloride on cognition of patients undergoing ECT. A triple blind (the study subjects, clinician assessing the cognition, and the data analyst were unaware of subject allocation for trial assessment) randomized controlled trial was carried out in a General Hospital Psychiatry Unit. Subjects were randomized into 2 groups. One group received ECT with placebo, whereas the other group received ECT and donepezil (a memory-enhancing drug). Study participants were assessed in post-ECT period to analyze cognitive deficits and to compare the differences in 2 groups, as regards recovery of various aspects of cognition. The post-ECT recovery of various components of cognition was more rapid in patients using donepezil as compared to those not given donepezil (P < 0.05). This significant improvement in recovery time among patients receiving donepezil bears therapeutic implication in immediate post-ECT cognitive deficits.

Negative inductance circuits for metamaterial bandwidth enhancement

NASA Astrophysics Data System (ADS)

Avignon-Meseldzija, Emilie; Lepetit, Thomas; Ferreira, Pietro Maris; Boust, Fabrice

2017-12-01

Passive metamaterials have yet to be translated into applications on a large scale due in large part to their limited bandwidth. To overcome this limitation many authors have suggested coupling metamaterials to non-Foster circuits. However, up to now, the number of convincing demonstrations based on non-Foster metamaterials has been very limited. This paper intends to clarify why progress has been so slow, i.e., the fundamental difficulty in making a truly broadband and efficient non-Foster metamaterial. To this end, we consider two families of metamaterials, namely Artificial Magnetic Media and Artificial Magnetic Conductors. In both cases, it turns out that bandwidth enhancement requires negative inductance with almost zero resistance. To estimate bandwidth enhancement with actual non-Foster circuits, we consider two classes of such circuits, namely Linvill and gyrator. The issue of stability being critical, both metamaterial families are studied with equivalent circuits that include advanced models of these non-Foster circuits. Conclusions are different for Artificial Magnetic Media coupled to Linvill circuits and Artificial Magnetic Conductors coupled to gyrator circuits. In the first case, requirements for bandwidth enhancement and stability are very hard to meet simultaneously whereas, in the second case, an adjustment of the transistor gain does significantly increase bandwidth.

Detection of candidate biomarkers of prostate cancer progression in serum: a depletion-free 3D LC/MS quantitative proteomics pilot study.

PubMed

Larkin, S E T; Johnston, H E; Jackson, T R; Jamieson, D G; Roumeliotis, T I; Mockridge, C I; Michael, A; Manousopoulou, A; Papachristou, E K; Brown, M D; Clarke, N W; Pandha, H; Aukim-Hastie, C L; Cragg, M S; Garbis, S D; Townsend, P A

2016-10-25

Prostate cancer (PCa) is the most common male cancer in the United Kingdom and we aimed to identify clinically relevant biomarkers corresponding to stage progression of the disease. We used enhanced proteomic profiling of PCa progression using iTRAQ 3D LC mass spectrometry on high-quality serum samples to identify biomarkers of PCa. We identified >1000 proteins. Following specific inclusion/exclusion criteria we targeted seven proteins of which two were validated by ELISA and six potentially interacted forming an 'interactome' with only a single protein linking each marker. This network also includes accepted cancer markers, such as TNF, STAT3, NF-κB and IL6. Our linked and interrelated biomarker network highlights the potential utility of six of our seven markers as a panel for diagnosing PCa and, critically, in determining the stage of the disease. Our validation analysis of the MS-identified proteins found that SAA alongside KLK3 may improve categorisation of PCa than by KLK3 alone, and that TSR1, although not significant in this model, might also be a clinically relevant biomarker.

A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin

PubMed Central

Doctrow, Susan R.; Lopez, Argelia; Schock, Ashley M.; Duncan, Nathan E.; Jourdan, Megan M.; Olasz, Edit B.; Moulder, John E.; Fish, Brian L.; Mäder, Marylou; Lazar, Jozef; Lazarova, Zelmira

2012-01-01

In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 h after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress plays a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 h after exposure. PMID:23190879

Altered Fibroblast Growth Factor Receptor 4 Stability Promotes Prostate Cancer Progression1

PubMed Central

Wang, Jianghua; Yu, Wendong; Cai, Yi; Ren, Chengxi; Ittmann, Michael M

2008-01-01

Fibroblast growth factor receptor 4 (FGFR-4) is expressed at significant levels in almost all human prostate cancers, and expression of its ligands is ubiquitous. A common polymorphism of FGFR-4 in which arginine (Arg388) replaces glycine (Gly388) at amino acid 388 is associated with progression in human prostate cancer. We show that the FGFR-4 Arg388 polymorphism, which is present in most prostate cancer patients, results in increased receptor stability and sustained receptor activation. In patients bearing the FGFR-4 Gly388 variant, expression of Huntingtin-interacting protein 1 (HIP1), which occurs in more than half of human prostate cancers, also results in FGFR-4 stabilization. This is associated with enhanced proliferation and anchorage-independent growth in vitro. Our findings indicate that increased receptor stability and sustained FGFR-4 signaling occur in most human prostate cancers due to either the presence of a common genetic polymorphism or the expression of a protein that stabilizes FGFR-4. Both of these alterations are associated with clinical progression in patients with prostate cancer. Thus, FGFR-4 signaling and receptor turnover are important potential therapeutic targets in prostate cancer. PMID:18670643

Overexpression of Human Papillomavirus Type 16 Oncoproteins Enhances Epithelial-Mesenchymal Transition via STAT3 Signaling Pathway in Non-Small Cell Lung Cancer Cells.

PubMed

Zhang, Wenzhang; Wu, Xin; Hu, Liang; Ma, Yuefan; Xiu, Zihan; Huang, Bingyu; Feng, Yun; Tang, Xudong

2017-05-24

The human papillomavirus (HPV) infection may be associated with the development and progression of non-small cell lung cancer (NSCLC). However, the role of HPV-16 oncoproteins in the development and progression of NSCLC is not completely clear. Epithelial-mesenchymal transition (EMT), a crucial step for invasion and metastasis, plays a key role in the development and progression of NSCLC. Here we explored the effect of HPV-16 oncoproteins on EMT and the underlying mechanisms. NSCLC cell lines, A549 and NCI-H460, were transiently transfected with the EGFP-N1-HPV-16 E6 or E7 plasmid. Real-time PCR and Western blot analysis were performed to analyze the expression of EMT markers. A protein microarray was used to screen the involved signaling pathway. Our results showed that overexpression of HPV-16 E6 and E7 oncoproteins in NSCLC cells significantly promoted EMT-like morphologic changes, downregulated the mRNA and protein levels of EMT epithelial markers (E-cadherin and ZO-1), and upregulated the mRNA and protein levels of EMT mesenchymal markers (N-cadherin and vimentin) and transcription factors (ZEB-1 and Snail-1). Furthermore, the HPV-16 E6 oncoprotein promoted STAT3 activation. Moreover, WP1066, a specific signal transducer and activator of transcription 3 (STAT3) inhibitor, reversed the effect of HPV-16 E6 on the expression of ZO-1, vimentin, and ZEB-1 in transfected NSCLC cells. Taken together, our results suggest that overexpression of HPV-16 E6 and E7 oncoproteins enhances EMT, and the STAT3 signaling pathway may be involved in HPV-16 E6-induced EMT in NSCLC cells.

Particulate matter induced enhancement of inflammatory markers in the brains of apolipoprotein E knockout mice.

PubMed

Campbell, Arezoo; Araujo, Jesus A; Li, Huihui; Sioutas, Constantinos; Kleinman, Michael

2009-08-01

Exposure to air particulate matter (PM) present in urban environments have been shown to induce systemic prooxidant and proinflammatory effects in apolipoprotein E knockout (ApoE-/-) mice and proinflammatory central nervous system (CNS) effects in BALB/c mice. We hypothesize that ApoE-/- mice would exhibit a greater propensity to develop PM-induced CNS effects due to their greater susceptibility to CNS inflammation. We studied the brains of ApoE-/- mice exposed in a previous study to concentrated air particles of different sizes (fine vs. ultrafine) or filtered-air to evaluate the effect of PM exposure on the development of CNS proinflammatory effects in a genetically susceptible background. This was important because, although the use of nano-sized materials opens an exciting potential for their use as diagnostic or therapeutic tools, not much is known about the possible CNS toxicity of these particles. Neuroinflammation has been shown to exacerbate progression of neurodegeneration. Since the onset and progression of idiopathic forms of neurodegenerative disorders are likely to be multifactorial and involve gene-environment interactions, we determined the possibility of particles in ambient air pollution to enhance neuroinflammation. Our results indicate that in the brain, there was significant modulation in the activation of the transcription factors NF-kappaB and AP-1 after exposure to the ultrafine fractions. Levels of two pro-inflammatory cytokines (TNF-alpha and IL-1alpha) were also increased in the brain of exposed animals and this was independent of the size fraction of PM. Since inflammatory processes have been shown to contribute to the pathology associated with neurodegenerative diseases, it will be important to further evaluate the role ambient particles may play in the potentiation of existing CNS damage and progression of neurodegenerative disorders.

3-Dimensional magnetic resonance spectroscopic imaging at 3 Tesla for early response assessment of glioblastoma patients during external beam radiation therapy.

PubMed

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-09-01

To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al. MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. Published by Elsevier Inc.

3D-MR Spectroscopic Imaging at 3Tesla for Early Response Assessment of Glioblastoma Patients during External Beam Radiation Therapy

PubMed Central

Muruganandham, Manickam; Clerkin, Patrick P; Smith, Brian J; Anderson, Carryn M; Morris, Ann; Capizzano, Aristides A; Magnotta, Vincent; McGuire, Sarah M; Smith, Mark C; Bayouth, John E; Buatti, John M

2014-01-01

Purpose To evaluate the utility of 3D-MR proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium enhanced MR images at simulation and at boost treatment planning after 17-20 fractions of radiotherapy. All patients received standard radiotherapy with temozolomide and follow-up with every two month MR scans. Progression free survival was defined using MacDonald criteria. MRSI images obtained at initial simulation were analyzed for choline / N-acetylaspartate ratios (Cho/NAA) on a voxel by voxel basis with abnormal activity defined as Cho/NAA ≥ 2. These images were compared on anatomically matched MRSI data collected after 3 weeks of radiotherapy. Changes in Cho/NAA between pre-therapy and 3rd week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results After 8.6 months (median follow-up), 50% of patients had progressed based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (p< 0.01). Patients with an increase in mean or median Cho/NAA values at the 3rd week RT scan had a significantly greater chance of early progression (p <0.01). An increased Cho/NAA at the 3rd week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval 1.10-6.71, p= 0.03). Most patients received the prescription dose of RT to the Cho/NAA ≥ 2 volume, which was where recurrence most often occurred. Conclusion Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested. PMID:24986746

3-Dimensional Magnetic Resonance Spectroscopic Imaging at 3 Tesla for Early Response Assessment of Glioblastoma Patients During External Beam Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Muruganandham, Manickam; Clerkin, Patrick P.; Smith, Brian J.

Purpose: To evaluate the utility of 3-dimensional magnetic resonance (3D-MR) proton spectroscopic imaging for treatment planning and its implications for early response assessment in glioblastoma multiforme. Methods and Materials: Eighteen patients with newly diagnosed, histologically confirmed glioblastoma had 3D-MR proton spectroscopic imaging (MRSI) along with T2 and T1 gadolinium-enhanced MR images at simulation and at boost treatment planning after 17 to 20 fractions of radiation therapy. All patients received standard radiation therapy (RT) with concurrent temozolomide followed by adjuvant temozolomide. Imaging for response assessment consisted of MR scans every 2 months. Progression-free survival was defined by the criteria of MacDonald et al.more » MRSI images obtained at initial simulation were analyzed for choline/N-acetylaspartate ratios (Cho/NAA) on a voxel-by-voxel basis with abnormal activity defined as Cho/NAA ≥2. These images were compared on anatomically matched MRSI data collected after 3 weeks of RT. Changes in Cho/NAA between pretherapy and third-week RT scans were tested using Wilcoxon matched-pairs signed rank tests and correlated with progression-free survival, radiation dose and location of recurrence using Cox proportional hazards regression. Results: After a median follow-up time of 8.6 months, 50% of patients had experienced progression based on imaging. Patients with a decreased or stable mean or median Cho/NAA values had less risk of progression (P<.01). Patients with an increase in mean or median Cho/NAA values at the third-week RT scan had a significantly greater chance of early progression (P<.01). An increased Cho/NAA at the third-week MRSI scan carried a hazard ratio of 2.72 (95% confidence interval, 1.10-6.71; P=.03). Most patients received the prescription dose of RT to the Cho/NAA ≥2 volume, where recurrence most often occurred. Conclusion: Change in mean and median Cho/NAA detected at 3 weeks was a significant predictor of early progression. The potential impact for risk-adaptive therapy based on early spectroscopic findings is suggested.« less

The PHD Finger Protein MMD1/DUET Ensures the Progression of Male Meiotic Chromosome Condensation and Directly Regulates the Expression of the Condensin Gene CAP-D3.

PubMed

Wang, Jun; Niu, Baixiao; Huang, Jiyue; Wang, Hongkuan; Yang, Xiaohui; Dong, Aiwu; Makaroff, Christopher; Ma, Hong; Wang, Yingxiang

2016-08-01

Chromosome condensation, a process mediated by the condensin complex, is essential for proper chromosome segregation during cell division. Unlike rapid mitotic chromosome condensation, meiotic chromosome condensation occurs over a relatively long prophase I and is unusually complex due to the coordination with chromosome axis formation and homolog interaction. The molecular mechanisms that regulate meiotic chromosome condensation progression from prophase I to metaphase I are unclear. Here, we show that the Arabidopsis thaliana meiotic PHD-finger protein MMD1/DUET is required for progressive compaction of prophase I chromosomes to metaphase I bivalents. The MMD1 PHD domain is required for its function in chromosome condensation and binds to methylated histone tails. Transcriptome analysis and qRT-PCR showed that several condensin genes exhibit significantly reduced expression in mmd1 meiocytes. Furthermore, MMD1 specifically binds to the promoter region of the condensin subunit gene CAP-D3 to enhance its expression. Moreover, cap-d3 mutants exhibit similar chromosome condensation defects, revealing an MMD1-dependent mechanism for regulating meiotic chromosome condensation, which functions in part by promoting condensin gene expression. Together, these discoveries provide strong evidence that the histone reader MMD1/DUET defines an important step for regulating the progression of meiotic prophase I chromosome condensation. © 2016 American Society of Plant Biologists. All rights reserved.

The PHD Finger Protein MMD1/DUET Ensures the Progression of Male Meiotic Chromosome Condensation and Directly Regulates the Expression of the Condensin Gene CAP-D3[OPEN

PubMed Central

Wang, Jun; Niu, Baixiao; Huang, Jiyue; Wang, Hongkuan; Yang, Xiaohui; Dong, Aiwu

2016-01-01

Chromosome condensation, a process mediated by the condensin complex, is essential for proper chromosome segregation during cell division. Unlike rapid mitotic chromosome condensation, meiotic chromosome condensation occurs over a relatively long prophase I and is unusually complex due to the coordination with chromosome axis formation and homolog interaction. The molecular mechanisms that regulate meiotic chromosome condensation progression from prophase I to metaphase I are unclear. Here, we show that the Arabidopsis thaliana meiotic PHD-finger protein MMD1/DUET is required for progressive compaction of prophase I chromosomes to metaphase I bivalents. The MMD1 PHD domain is required for its function in chromosome condensation and binds to methylated histone tails. Transcriptome analysis and qRT-PCR showed that several condensin genes exhibit significantly reduced expression in mmd1 meiocytes. Furthermore, MMD1 specifically binds to the promoter region of the condensin subunit gene CAP-D3 to enhance its expression. Moreover, cap-d3 mutants exhibit similar chromosome condensation defects, revealing an MMD1-dependent mechanism for regulating meiotic chromosome condensation, which functions in part by promoting condensin gene expression. Together, these discoveries provide strong evidence that the histone reader MMD1/DUET defines an important step for regulating the progression of meiotic prophase I chromosome condensation. PMID:27385818

Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.

PubMed

Orozco, Carlos A; Martinez-Bosch, Neus; Guerrero, Pedro E; Vinaixa, Judith; Dalotto-Moreno, Tomás; Iglesias, Mar; Moreno, Mireia; Djurec, Magdolna; Poirier, Françoise; Gabius, Hans-Joachim; Fernandez-Zapico, Martin E; Hwang, Rosa F; Guerra, Carmen; Rabinovich, Gabriel A; Navarro, Pilar

2018-04-17

Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras -driven mouse model of PDA ( Ela-Kras G12V p53 -/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.

Combined Secretomics and Transcriptomics Revealed Cancer-Derived GDF15 is Involved in Diffuse-Type Gastric Cancer Progression and Fibroblast Activation.

PubMed

Ishige, Takayuki; Nishimura, Motoi; Satoh, Mamoru; Fujimoto, Mai; Fukuyo, Masaki; Semba, Toshihisa; Kado, Sayaka; Tsuchida, Sachio; Sawai, Setsu; Matsushita, Kazuyuki; Togawa, Akira; Matsubara, Hisahiro; Kaneda, Atsushi; Nomura, Fumio

2016-02-19

Gastric cancer is classified into two subtypes, diffuse and intestinal. The diffuse-type gastric cancer (DGC) has poorer prognosis, and the molecular pathology is not yet fully understood. The purpose of this study was to identify functional secreted molecules involved in DGC progression. We integrated the secretomics of six gastric cancer cell lines and gene expression analysis of gastric cancer tissues with publicly available microarray data. Hierarchical clustering revealed characteristic gene expression differences between diffuse- and intestinal-types. GDF15 was selected as a functional secreted molecule owing to high expression only in fetal tissues. Protein expression of GDF15 was higher in DGC cell lines and tissues. Serum levels of GDF15 were significant higher in DGC patients as compared with healthy individuals and chronic gastritis patients, and positively correlated with wall invasion and lymph node metastasis. In addition, the stimulation of GDF15 on NIH3T3 fibroblast enhanced proliferation and up-regulated expression of extracellular matrix genes, which were similar to TGF-β stimulation. These results indicate that GDF15 contributes to fibroblast activation. In conclusion, this study revealed that GDF15 may be a novel functional secreted molecule for DGC progression, possibly having important roles for cancer progression via the affecting fibroblast function, as well as TGF-β.

Mobilizing community-based health insurance to enhance awareness & prevention of airborne, vector-borne & waterborne diseases in rural India.

PubMed

Panda, Pradeep; Chakraborty, Arpita; Dror, David M

2015-08-01

Despite remarkable progress in airborne, vector-borne and waterborne diseases in India, the morbidity associated with these diseases is still high. Many of these diseases are controllable through awareness and preventive practice. This study was an attempt to evaluate the effectiveness of a preventive care awareness campaign in enhancing knowledge related with airborne, vector-borne and waterborne diseases, carried out in 2011 in three rural communities in India (Pratapgarh and Kanpur-Dehat in Uttar Pradesh and Vaishali in Bihar). Data for this analysis were collected from two surveys, one done before the campaign and the other after it, each of 300 randomly selected households drawn from a larger sample of Self-Help Groups (SHGs) members invited to join community-based health insurance (CBHI) schemes. The results showed a significant increase both in awareness (34%, p<0.001) and in preventive practices (48%, P=0.001), suggesting that the awareness campaign was effective. However, average practice scores (0.31) were substantially lower than average awareness scores (0.47), even in post-campaign. Awareness and preventive practices were less prevalent in vector-borne diseases than in airborne and waterborne diseases. Education was positively associated with both awareness and practice scores. The awareness scores were positive and significant determinants of the practice scores, both in the pre- and in the post-campaign results. Affiliation to CBHI had significant positive influence on awareness and on practice scores in the post-campaign period. The results suggest that well-crafted health educational campaigns can be effective in raising awareness and promoting health-enhancing practices in resource-poor settings. It also confirms that CBHI can serve as a platform to enhance awareness to risks of exposure to airborne, vector-borne and waterborne diseases, and encourage preventive practices.

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy.

PubMed

Conte, Antonella; Belvisi, Daniele; Bologna, Matteo; Ottaviani, Donatella; Fabbrini, Giovanni; Colosimo, Carlo; Williams, David R; Berardelli, Alfredo

2012-03-01

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.

Id-1 promotes osteosarcoma cell growth and inhibits cell apoptosis via PI3K/AKT signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hao, Liang; Liao, Qi; Tang, Qiang

2016-02-12

Accumulating evidence reveals that Id-1 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the role of Id-1 in osteosarcoma (OS) is unknown. In present study, we found that Id-1 expression was elevated in OS tissues than adjacent normal bone tissues. More importantly, we demonstrated that overexpression of Id-1 is significantly correlated with tumor progression and poor survival in OS patients. Furthermore, increased expression of Id-1 was observed in OS cell lines and ectopic expression of Id-1 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas knockdown of Id-1 suppressed OS cellsmore » growth. Moreover, our experimental data revealed that Id-1 promotes cell proliferation by facilitating cell cycle progression and inhibits cell apoptosis. Mechanistically, the effects of Id-1 in OS cells is at least partly through activation of PI3K/Akt signaling pathway. Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients. - Highlights: • Id-1 expression is positively correlated in OS patients with poor prognosis. • Overexpression of Id-1 promotes OS cell growth in vitro and in vivo. • Id-1induces cell cycle progression and inhibits cell apoptosis. • PI3K/Akt signaling pathway contributed to the oncogenic effects of Id-1 in OS cells.« less

Proteomic Analysis of Metabolic Responses to Biofuels and Chemicals in Photosynthetic Cyanobacteria.

PubMed

Sun, T; Chen, L; Zhang, W

2017-01-01

Recent progresses in various "omics" technologies have enabled quantitative measurements of biological molecules in a high-throughput manner. Among them, high-throughput proteomics is a rapidly advancing field that offers a new means to quantify metabolic changes at protein level, which has significantly facilitated our understanding of cellular process, such as protein synthesis, posttranslational modifications, and degradation in responding to environmental perturbations. Cyanobacteria are autotrophic prokaryotes that can perform oxygenic photosynthesis and have recently attracted significant attentions as one promising alternative to traditionally biomass-based "microbial cell factories" to produce green fuels and chemicals. However, early studies have shown that the low tolerance to toxic biofuels and chemicals represented one major hurdle for further improving productivity of the cyanobacterial production systems. To address the issue, metabolic responses and their regulation of cyanobacterial cells to toxic end-products need to be defined. In this chapter, we discuss recent progresses in interpreting cyanobacterial responses to biofuels and chemicals using high-throughput proteomics approach, aiming to provide insights and guidelines on how to enhance tolerance and productivity of biofuels or chemicals in the renewable cyanobacteria systems in the future. © 2017 Elsevier Inc. All rights reserved.

Optimization of genetics to create therapies for metastatic (stage IV) non-small-cell lung cancer.

PubMed

Rosell, Rafael; Moran, Teresa; Viteri, Santiago; Carcereny, Enric; Gasco, Amaya; Quiroga, Vanessa; Wei, Jia; Camps, Carlos; Massuti, Bartomeu

2010-07-01

Non-small-cell lung cancer (NSCLC) is a disseminated disease in 50% of cases, with a gloomy prognosis and median survivals of < 1 year. Based on substantial advances, cancer biology insights and novel biotechnology tools, customized treatment provides hints that cisplatin-based treatment can be optimized in favorable subgroups of patients according to gene expression DNA repair profiles. In 2004, it was discovered that 10-15% of NSCLC can harbor a new class of EGFR mutation conferring specific sensitivity to EGFR tyrosine kinase inhibitors. The homologous recombination pathway provides information for customizing cisplatin-based chemotherapy. BRCA1 plays a central role in this pathway that can be used in tailoring chemotherapy. Patient subgroups can obtain significant increases in progression-free survival. For EGFR lung-addicted cancers, treatment with EGFR tyrosine kinase inhibitors like erlotinib provide impressive improvement in progression-free survival--up to 14 months with significant enhanced survival. Customized chemotherapy based on BRCA1 models can contribute to demonstrating this approach's clinical relevance, and the implementation of EGFR mutation assessment is warranted to identify EGFR-addicted lung cancers with a different prognosis that could benefit from a specifically targeted therapy approach.

A study of morphology, provenance, and movement of desert sand seas in Africa, Asia, and Australia

NASA Technical Reports Server (NTRS)

Mckee, E. D. (Principal Investigator); Breed, C. S.

1973-01-01

The author has identified the following significant results. Recent acquisition of generally high quality color prints for most of the test sites has enabled the project to make significant advances in preparing mosaics of sand desert areas under study. Computer enhancement of imagery of selected sites, where details of complex dune forms need to be determined, has been achieved with arrival of computer-compatible ERTS-1 tapes. Further, a comparator, recently received, gives precise visual measurements of width, length, and spacing of sand bodies and so improves comparison of patterns in various test sites. Considerable additional meteorological data recently received on sand-moving winds in China, Pakistan, Libya and other areas enabled much progress to be made in developing overlays for the dune mosaics. These data show direction, speed, and frequency of winds. Other new data for use in preparing overlays used with ERTS-1 image mosaics include ground truth on moisture control, geologic settings, and plant distribution. With the addition of visual observation data and prints from hand-held photography now being obtained by the Skylab mission, much progress in interpreting the patterns of sand seas for 17 desert sites is anticipated.

A study of morphology, provenance, and movement of desert sand seas in Africa, Asia, and Australia

NASA Technical Reports Server (NTRS)

Mckee, E. D. (Principal Investigator); Breed, C. S.

1974-01-01

The author has identified the following significant results. Recent acquisition of generally high quality color prints for most of the test sites has enabled this project to make significant advances in preparing mosaics of sand desert areas under study. Computer enhancement of imagery, where details of complex dune forms need to be determined, has been achieved with arrival of computer-compatible ERTS-1 tapes. Further, a comparator, recently received, gives precise visual measurements of width, length, and spacing of sand bodies and so improves comparison of patterns in various test sites. Considerable additional meteorological data recently received on sand-moving winds in China, Pakistan, Libya, and other study areas enabled much progress to be made in developing overlays for the dune mosaics. These data show direction, speed, and frequency of winds. Other new data for use in preparing overlays used with ERTS-1 image mosaics include ground truth on moisture control, geologic settings, and plant distribution. With the addition of visual observation data and prints from hand-held photography now being obtained by the Skylab 4 mission, much progress in interpreting the patterns of sand seas for 17 desert sites is anticipated.

The free and cued selective reminding test for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: A prospective longitudinal study.

PubMed

Lemos, Raquel; Marôco, João; Simões, Mário R; Santiago, Beatriz; Tomás, José; Santana, Isabel

2017-03-01

Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow-up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker. © 2015 The British Psychological Society.

Fibulin-1 Predicts Disease Progression in Patients With Idiopathic Pulmonary Fibrosis

PubMed Central

Unger, Sofia; Corte, Tamera J.; Keller, Michael; Wolters, Paul J.; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M.; Hansbro, Philip M.; Argraves, William Scott; Oliver, Rema A.; Oliver, Brian G.; Black, Judith L.; Burgess, Janette K.

2014-01-01

BACKGROUND: The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. METHODS: Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. RESULTS: Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = −0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). CONCLUSIONS: Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments. PMID:24832167

Predictive Value of Early Tumor Shrinkage and Density Reduction of Lung Metastases in Patients With Metastatic Colorectal Cancer Treated With Regorafenib.

PubMed

Vanwynsberghe, Hannes; Verbeke, Xander; Coolen, Johan; Van Cutsem, Eric

2017-12-01

The benefit of regorafenib in colorectal cancer is not very pronounced. At present, there is lack of predictive biological or radiological markers. We studied if density reduction or small changes in size of lung metastases could be a predictive marker. We retrospectively measured density in size of lung metastases of all patients included in the CORRECT and CONSIGN trials at our center. Contrast-enhanced CT scan at baseline and at week 8 were compared. Data of progressive-free survival and overall survival were collected from the CORRECT and CONSIGN trials. A significant difference in progressive-free survival was seen in 3 groups: response or stable disease in size (5.36 vs. 3.96 months), response in density (6.03 vs. 2.72 months), and response in corrected density (6.14 vs. 3.08 months). No difference was seen for response in size versus stable disease or progressive disease in size. For overall survival, a difference was observed in the same 3 groups: response or stable disease in size (9.89 vs. 6.44 months), response in density (9.59 vs. 7.04 months), and response in corrected density (9.09 vs. 7.16 months). No difference was seen for response in size versus stable disease or progressive disease in size. Density reduction in lung metastases might be a good predictive parameter to predict outcome for regorafenib. Early tumor progression might be a negative predictive factor. If further validated, density reduction and early tumor progression might be useful to ameliorate the cost-benefit of regorafenib. Copyright © 2017 Elsevier Inc. All rights reserved.

Fibulin-1 predicts disease progression in patients with idiopathic pulmonary fibrosis.

PubMed

Jaffar, Jade; Unger, Sofia; Corte, Tamera J; Keller, Michael; Wolters, Paul J; Richeldi, Luca; Cerri, Stefania; Prêle, Cecilia M; Hansbro, Philip M; Argraves, William Scott; Oliver, Rema A; Oliver, Brian G; Black, Judith L; Burgess, Janette K

2014-10-01

The underlying mechanisms of idiopathic pulmonary fibrosis (IPF) are unknown. This progressive disease has high mortality rates, and current models for prediction of mortality have limited value in identifying which patients will progress. We previously showed that the glycoprotein fibulin-1 is involved in enhanced proliferation and wound repair by mesenchymal cells and, thus, may contribute to lung fibrosis in IPF. Serum, lung tissue, and lung function values were obtained from four independent locations (Sydney, NSW, and Perth, WA, Australia; San Francisco, CA; and Modena, Italy). Patients with IPF were followed for a minimum of 1 year and progression was defined as a significant decline in lung function or death. Primary parenchymal lung fibroblasts of 15 patients with and without IPF were cultured under nonstimulatory conditions. Fibulin-1 levels in serum, and secreted or deposited by fibroblasts, were measured by western blot and in lung tissue by immunohistochemistry. Serum fibulin-1 levels were increased in patients with IPF compared with subjects without lung disease (P = .006). Furthermore, tissue fibulin-1 levels were increased in patients with IPF (P = .02) and correlated negatively with lung function (r = -0.9, P < .05). Primary parenchymal fibroblasts from patients with IPF produced more fibulin-1 than those from subjects without IPF (P < .05). Finally, serum fibulin-1 levels at first blood draw predicted disease progression in IPF within 1 year (area under the curve , 0.71; 95% CI, 0.57-0.86; P = .012). Fibulin-1 is a novel potential biomarker for disease progression in IPF and raises the possibility that it could be used as a target for the development of new treatments.

The role of Fas ligand and transforming growth factor beta in tumor progression: molecular mechanisms of immune privilege via Fas-mediated apoptosis and potential targets for cancer therapy.

PubMed

Kim, Ryungsa; Emi, Manabu; Tanabe, Kazuaki; Uchida, Yoko; Toge, Tetsuya

2004-06-01

Despite the fact that expression of Fas ligand (FasL) in cytotoxic T lymphocytes (CTLs) and in natural killer (NK) cells plays an important role in Fas-mediated tumor killing, During tumor progression FasL-expressing tumor cells are involved in counterattacking to kill tumor-infiltrating lymphocytes (TILs). Soluble FasL levels also increase with tumor progression in solid tumors, and this increase inhibits Fas-mediated tumor killing by CTLs and NK cells. The increased expression of FasL in tumor cells is associated with decreased expression of Fas; and the promoter region of the FASL gene is regulated by transcription factors, such as neuronal factor kappaB (NF-kappaB) and AP-1, in the tumor microenvironment. Although the ratio of FasL expression to Fas expression in tumor cells is not strongly related to the induction of apoptosis in TILs, increased expression of FasL is associated with decreased Fas levels in tumor cells that can escape immune surveillance and facilitate tumor progression and metastasis. Transforming growth factor beta (TGF-beta) is a potent growth inhibitor and has tumor-suppressing activity in the early phases of carcinogenesis. During subsequent tumor progression, the increased secretion of TGF-beta by both tumor cells and, in a paracrine fashion, stromal cells, is involved in the enhancement of tumor invasion and metastasis accompanied by immunosuppression. Herein, the authors review the clinical significance of FasL and TGF-beta expression patterns as features of immune privilege accompanying tumor progression in the tumor microenvironment. Potential strategies for identifying which molecules can serve as targets for effective antitumor therapy also are discussed. Copyright 2004 American Cancer Society.

20 CFR 411.180 - What is timely progress toward self-supporting employment?

Code of Federal Regulations, 2010 CFR

2010-04-01

... certificate or vocational or technical training that will enhance your ability to return to work. In addition...-secondary education requirement or vocational or technical training requirement in the applicable progress... this 12-month period; or (iv) You must have been enrolled in a vocational or technical training program...

Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

USDA-ARS?s Scientific Manuscript database

Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

Mena deficiency delays tumor progression and decreases metastasis in polyoma middle-T transgenic mouse mammary tumors.

PubMed

Roussos, Evanthia T; Wang, Yarong; Wyckoff, Jeffrey B; Sellers, Rani S; Wang, Weigang; Li, Jiufeng; Pollard, Jeffrey W; Gertler, Frank B; Condeelis, John S

2010-01-01

The actin binding protein Mammalian enabled (Mena), has been implicated in the metastatic progression of solid tumors in humans. Mena expression level in primary tumors is correlated with metastasis in breast, cervical, colorectal and pancreatic cancers. Cells expressing high Mena levels are part of the tumor microenvironment for metastasis (TMEM), an anatomical structure that is predictive for risk of breast cancer metastasis. Previously we have shown that forced expression of Mena adenocarcinoma cells enhances invasion and metastasis in xenograft mice. Whether Mena is required for tumor progression is still unknown. Here we report the effects of Mena deficiency on tumor progression, metastasis and on normal mammary gland development. To investigate the role of Mena in tumor progression and metastasis, Mena deficient mice were intercrossed with mice carrying a transgene expressing the polyoma middle T oncoprotein, driven by the mouse mammary tumor virus. The progeny were investigated for the effects of Mena deficiency on tumor progression via staging of primary mammary tumors and by evaluation of morbidity. Stages of metastatic progression were investigated using an in vivo invasion assay, intravital multiphoton microscopy, circulating tumor cell burden, and lung metastases. Mammary gland development was studied in whole mount mammary glands of wild type and Mena deficient mice. Mena deficiency decreased morbidity and metastatic dissemination. Loss of Mena increased mammary tumor latency but had no affect on mammary tumor burden or histologic progression to carcinoma. Elimination of Mena also significantly decreased epidermal growth factor (EGF) induced in vivo invasion, in vivo motility, intravasation and metastasis. Non-tumor bearing mice deficient for Mena also showed defects in mammary gland terminal end bud formation and branching. Deficiency of Mena decreases metastasis by slowing tumor progression and reducing tumor cell invasion and intravasation. Mena deficiency during development causes defects in invasive processes involved in mammary gland development. These findings suggest that functional intervention targeting Mena in breast cancer patients may provide a valuable treatment option to delay tumor progression and decrease invasion and metastatic spread leading to an improved prognostic outcome.

Epoch Analysis of On-Treatment Disability Progression Events over Time in the Tysabri Observational Program (TOP)

PubMed Central

Wiendl, Heinz; Butzkueven, Helmut; Kappos, Ludwig; Trojano, Maria; Pellegrini, Fabio; Paes, Dominic; Zhang, Annie; Belachew, Shibeshih

2016-01-01

Objective To evaluate the effect of natalizumab on disability progression beyond 2 years of treatment in clinical practice. Methods Analyses included the 496 relapsing-remitting multiple sclerosis (RRMS) patients among 5122 patients in the Tysabri Observational Program (TOP) who had completed 4 continuous years of natalizumab treatment and had baseline (study enrollment) and postbaseline Expanded Disability Status Scale (EDSS) assessments. Proportions of patients with 6-month or 12-month confirmed ≥1.0-point EDSS progression relative to baseline were compared in treatment months 1–24 and 25–48. Sensitivity analyses compared progression rates in months 13–24 and 25–36. Results Baseline characteristics appeared similar between the overall TOP population (N = 5122), patients who had completed 4 years of natalizumab treatment (n = 469), and patients eligible to complete 4 years in TOP who had discontinued natalizumab after 2 years of treatment (n = 514). Among 4-year completers, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased between months 1–24 and 25–48 of natalizumab treatment by 42% (from 10.9% to 6.3%; p < 0.01) and 52% (from 9.5% to 4.6%; p < 0.01), respectively. Few patients had 6-month or 12-month confirmed EDSS progression in both epochs (0.6% and 0.2%, respectively). Between months 13–24 and 25–36 of treatment, the proportion of patients with 6-month and 12-month confirmed EDSS progression decreased by 60% (from 7.5% to 3.0%; p < 0.01) and 58% (from 6.7% to 2.8%; p < 0.01), respectively. Significant reductions in disability progression events between months 13–24 and 25–36 were also observed in relapse-free patients. Conclusion In this observational study, the disability progression rate decreased further beyond 2 years of natalizumab treatment. Patients who responded well and remained on continuous natalizumab therapy for over 4 years had sustained and potentially enhanced reductions in EDSS progression over time. PMID:26771747

Biotin-Pt (IV)-indomethacin hybrid: A targeting anticancer prodrug providing enhanced cancer cellular uptake and reversing cisplatin resistance.

PubMed

Hu, Weiwei; Fang, Lei; Hua, Wuyang; Gou, Shaohua

2017-10-01

A Pt(IV) prodrug (2) composed of cancer-targeting biotin and nonsteroidal anti-inflammatory drug indomethacin in the axial positions of the six-coordinated octahedral geometry derived from cisplatin was developed, which could be highly accumulated in cancer cells more than normal ones and activated by endogenous reducing molecules to release cisplatin and indomethacin moieties simultaneously to inhibit tumor progression synergistically. In vitro assays revealed that 2 exhibited significantly selective inhibition to the tested cancer cell lines and sensitivity to cisplatin resistant cancer cells. Moreover, 2 presented cyclooxygenases inhibition properties to reduce tumor-associated inflammation, reduced the invasiveness of the highly aggressive PC-3 cells, and disrupted capillary-like tube formation in EA.hy926 cells. In all, this study offers a new strategy to enhance sensitivity and reduce toxicity of cisplatin. Copyright © 2017 Elsevier Inc. All rights reserved.

Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

PubMed Central

Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Ardolino, Michele; Fessler, Evelyn; Chen, Michelle B.; Krall, Jordan A.; DeCock, Jasmine; Zervantonakis, Ioannis K.; Iannello, Alexandre; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Kamm, Roger D.; Pittet, Mikael J.; Raulet, David H.; Weinberg, Robert A.

2016-01-01

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+ neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL-1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their crosstalk with host cells and disseminating carcinoma cells. PMID:27072748

PGK1 Drives Hepatocellular Carcinoma Metastasis by Enhancing Metabolic Process.

PubMed

Xie, Huijun; Tong, Guihui; Zhang, Yupei; Liang, Shu; Tang, Kairui; Yang, Qinhe

2017-07-27

During the proliferation and metastasis, the tumor cells prefer glycolysis (Warburg effect), but its exact mechanism remains largely unknown. In this study, we demonstrated that phosphoglycerate kinase 1 (PGK1) is an important enzyme in the pathway of metabolic glycolysis. We observed a significant overexpression of PGK1 in hepatocellular carcinoma tissues, and a correlation between PGK1 expression and poor survival of hepatocellular carcinoma patients. Also, the depletion of PGK1 dramatically reduced cancer cell proliferation and metastasis, indicating an oncogenic role of PGK1 in liver cancer progression. Further experiments showed that PGK1 played an important role in MYC -induced metabolic reprogramming, which led to an enhanced Warburg effect. Our results revealed a new effect of PGK1, which can provide a new treatment strategy for hepatocellular carcinoma, as PGK1 is used to indicate the prognosis of hepatocellular carcinoma (HCC).

78 FR 70415 - Federal Motor Vehicle Safety Standards; Occupant Crash Protection

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-25

...Completing the first initiative of NHTSA's 2007 ``NHTSA's Approach to Motorcoach Safety'' plan and one of the principal undertakings of DOT's 2009 Motorcoach Safety Action Plan, and fulfilling a statutory mandate of the Motorcoach Enhanced Safety Act of 2012, incorporated into the Moving Ahead for Progress in the 21st Century Act, this final rule amends the Federal motor vehicle safety standard (FMVSS) on occupant crash protection to require lap/shoulder seat belts for each passenger seating position in all new over-the-road buses, and in new buses other than over-the-road buses with a gross vehicle weight rating (GVWR) greater than 11,793 kilograms (kg) (26,000 pounds (lb), with certain exclusions. By requiring the passenger lap/ shoulder seat belts, this final rule significantly reduces the risk of fatality and serious injury in frontal crashes and the risk of occupant ejection in rollovers, thus considerably enhancing the safety of these vehicles.

Conservation biology in Asia: the major policy challenges.

PubMed

McNeely, Jeffrey A; Kapoor-Vijay, Promila; Zhi, Lu; Olsvig-Whittaker, Linda; Sheikh, Kashif M; Smith, Andrew T

2009-08-01

With about half the world's human population and booming economies, Asia faces numerous challenges to its biodiversity. The Asia Section of the Society for Conservation Biology has identified some key policy issues in which significant progress can be made. These include developing new sources of funding for forest conservation; identifying potential impacts of energy alternatives on the conservation of biodiversity; curbing the trade in endangered species of plants and animals; a special focus on the conservation of mountain biodiversity; enhancing relevant research; ensuring that conservation biology contributes to major international conventions and funding mechanisms; using conservation biology to build a better understanding of zoonotic diseases; more effectively addressing human-animal conflicts; enhancing community-based conservation; and using conservation biology to help address the pervasive water-deficit problems in much of Asia. These challenges can be met through improved regional cooperation among the relevant stakeholders.

Contrast Media for X-ray and Magnetic Resonance Imaging: Development, Current Status and Future Perspectives.

PubMed

Frenzel, Thomas; Lawaczeck, Rüdiger; Taupitz, Matthias; Jost, Gregor; Lohrke, Jessica; Sieber, Martin A; Pietsch, Hubertus

2015-09-01

Over the last 120 years, the extensive advances in medical imaging allowed enhanced diagnosis and therapy of many diseases and thereby improved the quality of life of many patient generations. From the beginning, all technical solutions and imaging procedures were combined with dedicated pharmaceutical developments of contrast media, to further enhance the visualization of morphology and physiology. This symbiosis of imaging hardware and contrast media development was of high importance for the development of modern clinical radiology. Today, all available clinically approved contrast media fulfill the highest requirements for clinical safety and efficacy. All new concepts to increase the efficacy of contrast media have also to consider the high clinical safety standards and cost of goods of current marketed contrast media. Nevertheless, diagnostic imaging will contribute significantly to the progresses in medicine, and new contrast media developments are mandatory to address the medical needs of the future.

Reducing resistance and denial by exercising ambivalence during the treatment of addiction.

PubMed

Shaffer, H J; Simoneau, G

2001-01-01

Stage change models and motivational enhancement therapies have significantly influenced the therapeutic tactics clinicians employ in the treatment of addictive behaviors. While motivational enhancement strategies have addressed client ambivalence to increase motivation to change, this article suggests that focusing on ambivalence during treatment has even wider clinical utility than previously thought. Resistance reduction concentrates on exercising ambivalence without an investment in clients changing, thereby strengthening client tolerance for ambivalent thoughts and feelings. Exercising ambivalence reduces resistance to treatment and change by validating a wide array of possible outcomes through detailed exploration of how a behavior pattern works for a client. Since resistance reduction does not require clients to want to change for therapy to progress, exploring the decision-making process becomes paramount. A general discussion of the resistance reduction model, ambivalence, and how clients present for treatment precedes clinical case examples.

Augmentation of chemokine production by severe acute respiratory syndrome coronavirus 3a/X1 and 7a/X4 proteins through NF-kappaB activation.

PubMed

Kanzawa, Noriyuki; Nishigaki, Kazuo; Hayashi, Takaya; Ishii, Yuichi; Furukawa, Souichi; Niiro, Ayako; Yasui, Fumihiko; Kohara, Michinori; Morita, Kouichi; Matsushima, Kouji; Le, Mai Quynh; Masuda, Takao; Kannagi, Mari

2006-12-22

Severe acute respiratory syndrome (SARS) is characterized by rapidly progressing respiratory failure resembling acute/adult respiratory distress syndrome (ARDS) associated with uncontrolled inflammatory responses. Here, we demonstrated that, among five accessory proteins of SARS coronavirus (SARS-CoV) tested, 3a/X1 and 7a/X4 were capable of activating nuclear factor kappa B (NF-kappaB) and c-Jun N-terminal kinase (JNK), and significantly enhanced interleukin 8 (IL-8) promoter activity. Furthermore, 3a/X1 and 7a/X4 expression in A549 cells enhanced production of inflammatory chemokines that were known to be up-regulated in SARS-CoV infection. Our results suggest potential involvement of 3a/X1 and 7a/X4 proteins in the pathological inflammatory responses in SARS.

Transdermal drug delivery

PubMed Central

Prausnitz, Mark R.; Langer, Robert

2009-01-01

Transdermal drug delivery has made an important contribution to medical practice, but has yet to fully achieve its potential as an alternative to oral delivery and hypodermic injections. First-generation transdermal delivery systems have continued their steady increase in clinical use for delivery of small, lipophilic, low-dose drugs. Second-generation delivery systems using chemical enhancers, non-cavitational ultrasound and iontophoresis have also resulted in clinical products; the ability of iontophoresis to control delivery rates in real time provides added functionality. Third-generation delivery systems target their effects to skin’s barrier layer of stratum corneum using microneedles, thermal ablation, microdermabrasion, electroporation and cavitational ultrasound. Microneedles and thermal ablation are currently progressing through clinical trials for delivery of macromolecules and vaccines, such as insulin, parathyroid hormone and influenza vaccine. Using these novel second- and third-generation enhancement strategies, transdermal delivery is poised to significantly increase impact on medicine. PMID:18997767

Infrared point sensors for homeland defense applications

NASA Astrophysics Data System (ADS)

Thomas, Ross C.; Carter, Michael T.; Homrighausen, Craig L.

2004-03-01

We report recent progress toward the development of infrared point sensors for the detection of chemical warfare agents and explosive related chemicals, which pose a significant threat to both health and environment. Technical objectives have focused on the development of polymer sorbents to enhance the infrared response of these hazardous organic compounds. For example, infrared point sensors which part-per-billion detection limits have been developed that rapidlypartition chemical warfare agents and explosive related chemicals into polymer thin films with desirable chemical and physical properties. These chemical sensors demonstrate novel routes to reversible sensing of hazardous organic compounds. The development of small, low-power, sensitive, and selective instruments employing these chemical sensors would enhance the capabilities of federal, state, and local emergency response to incidents involving chemical terrorism. Specific applications include chemical defense systems for military personnel and homeland defense, environmental monitors for remediation and demilitarization, and point source detectors for emergency and maintenance response teams.

Hsp70: a chaperokine.

PubMed

Asea, Alexzander

2008-01-01

Chaperokine is a term recently coined to better describe the dual role of extracellular heat shock protein as both chaperone and cytokine. The augmentation of intracellular Hsp72 expression has clearly been demonstrated to be cytoprotective; with the ability to activate anti-apoptotic and anti-inflammatory pathways, exerting inhibitory effects on cell cycle progression and suppressing genes important in proliferation and differentiation. On the other hand, the role of extracellular Hsp72 is only now being elucidated and has been demonstrated to play a cytostimulatory role by enhancing proinflammatory cytokine and chemokine synthesis, up-regulate co-stimulatory molecule expression, enhance the maturation of dendritic cells and promote antitumour surveillance. This paper covers the most recent advances in elucidation of the mechanism by which the chaperokine activity of Hsp72 is transduced, addresses its biological significance and, finally, covers how it is being harnessed to produce novel therapeutic agents.

[Effect of inhibitors serine/threonine protein kinases and protein phosphatases on mitosis progression of synchronized tobacco by-2 cells].

PubMed

Sheremet, Ia A; Emets, A I; Azmi, A; Vissenberg, K; Verbelen, J-P; Blium, Ia B

2012-01-01

In order to investigate the role of various serine/ threonine protein kinases and protein phosphatases in the regulation of mitosis progression in plant cells the influence of cyclin-dependent (olomoucine) and Ca2+ -calmodulin-dependent (W7) protein kinases inhibitors, as well as protein kinase C inhibitors (H7 and staurosporine) and protein phosphatases inhibitor (okadaic acid) on mitosis progression in synchronized tobacco BY-2 cells has been studied. It was found that BY-2 culture treatment with inhibitors of cyclin dependent protein kinases and protein kinase C causes prophase delay, reduces the mitotic index and displaces of mitotic peak as compare with control cells. Inhibition of Ca2+ -calmodulin dependent protein kinases enhances the cell entry into prophase and delays their exit from mitosis. Meanwhile inhibition of serine/threonine protein phosphatases insignificantly enhances of synchronized BY-2 cells entering into all phases of mitosis.

An enhancement to the NA4 gear vibration diagnostic parameter

NASA Technical Reports Server (NTRS)

Decker, Harry J.; Handschuh, Robert F.; Zakrajsek, James J.

1994-01-01

A new vibration diagnostic parameter for health monitoring of gears, NA4*, is proposed and tested. A recently developed gear vibration diagnostic parameter NA4 outperformed other fault detection methods at indicating the start and initial progression of damage. However, in some cases, as the damage progressed, the sensitivity of the NA4 and FM4 parameters tended to decrease and no longer indicated damage. A new parameter, NA4* was developed by enhancing NA4 to improve the trending of the parameter. This allows for the indication of damage both at initiation and also as the damage progresses. The NA4* parameter was verified and compared to the NA4 and FM4 parameters using experimental data from single mesh spur and spiral bevel gear fatigue rigs. The primary failure mode for the test cases was naturally occurring tooth surface pitting. The NA4* parameter is shown to be a more robust indicator of damage.

Nanoparticle radio-enhancement: principles, progress and application to cancer treatment

NASA Astrophysics Data System (ADS)

Kuncic, Zdenka; Lacombe, Sandrine

2018-01-01

Enhancement of radiation effects by high-atomic number nanoparticles (NPs) has been increasingly studied for its potential to improve radiotherapeutic efficacy. The underlying principle of NP radio-enhancement is the potential to release copious electrons into a nanoscale volume, thereby amplifying radiation-induced biological damage. While the vast majority of studies to date have focused on gold nanoparticles with photon radiation, an increasing number of experimental, theoretical and simulation studies have explored opportunities offered by other NPs (e.g. gadolinium, platinum, iron oxide, hafnium) and other therapeutic radiation sources such as ion beams. It is thus of interest to the research community to consolidate findings from the different studies and summarise progress to date, as well as to identify strategies that offer promising opportunities for clinical translation. This is the purpose of this Topical Review.

Progress with enhancing veterinary surveillance in the United Kingdom.

PubMed

Lysons, R E; Gibbens, J C; Smith, L H

2007-01-27

The UK has experienced various animal health events that have had national impact in recent years. In response, a ;Veterinary Surveillance Strategy' (VSS) was published in 2003, with the objective of enhancing and coordinating national veterinary surveillance practice in a way that would enable important animal health events to be detected and assessed more rapidly and reliably. The VSS adopts an integrated UK-wide approach, which includes widespread engagement with interested parties both within government and beyond. It proposes enhancing surveillance through improved collaboration; transparent and defensible prioritisation of government resources to surveillance; deriving better value from existing resources, and assuring quality of the surveillance reports and source data. This article describes progress with implementing the VSS, in particular the methodology for developing a functional network and creating an effective, quality-assured, information management system, RADAR.

Nutritionally Enhanced Food Crops; Progress and Perspectives

PubMed Central

Hefferon, Kathleen L.

2015-01-01

Great progress has been made over the past decade with respect to the application of biotechnology to generate nutritionally improved food crops. Biofortified staple crops such as rice, maize and wheat harboring essential micronutrients to benefit the world’s poor are under development as well as new varieties of crops which have the ability to combat chronic disease. This review discusses the improvement of the nutritional status of crops to make a positive impact on global human health. Several examples of nutritionally enhanced crops which have been developed using biotechnological approaches will be discussed. These range from biofortified crops to crops with novel abilities to fight disease. The review concludes with a discussion of hurdles faced with respect to public perception, as well as directions of future research and development for nutritionally enhanced food crops. PMID:25679450

Environmentally relevant concentration of arsenic trioxide and humic acid promoted tumor progression of human cervical cancer cells: In vivo and in vitro studies.

PubMed

Tsai, Min-Ling; Yen, Cheng-Chieh; Lu, Fung-Jou; Ting, Hung-Chih; Chang, Horng-Rong

2016-09-01

In a previous study, treatment at higher concentrations of arsenic trioxide or co-exposure to arsenic trioxide and humic acid was found to be inhibited cell growth of cervical cancer cells (SiHa cells) by reactive oxygen species generation. However, treatment at lower concentrations slightly increased cell viability. Here, we investigate the enhancement of progression effects of environmentally relevant concentration of humic acid and arsenic trioxide in SiHa cell lines in vitro and in vivo by measuring cell proliferation, migration, invasion, and the carcinogenesis-related protein (MMP-2, MMP-9, and VEGF-A) expressions. SiHa cells treated with low concentrations of humic acid and arsenic trioxide alone or in co-exposure significantly increased reactive oxygen species, glutathione levels, cell proliferation, scratch wound-healing activities, migration abilities, and MMP-2 expression as compared to the untreated control. In vivo the tumor volume of either single drug (humic acid or arsenic trioxide) or combined drug-treated group was significantly larger than that of the control for an additional 45 days after tumor cell injection on the back of NOD/SCID mice. Levels of MMP-2, MMP-9, and VEGF-A, also significantly increased compared to the control. Histopathologic effects of all tumor cells appeared round in cell shape with high mitosis, focal hyperkeratosis and epidermal hyperplasia in the skin, and some tumor growth in the muscle were observed. Our results may indicate that exposure to low concentrations of arsenic trioxide and humic acid is associated with the progression of cervical cancer. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1121-1132, 2016. © 2015 Wiley Periodicals, Inc.

Recent Progress in SERS Biosensing

PubMed Central

Bantz, Kyle C.; Meyer, Audrey F.; Wittenberg, Nathan J.; Im, Hyungsoon; Kurtuluş, Özge; Lee, Si Hoon; Lindquist, Nathan C.

2011-01-01

This perspective gives an overview of recent developments in surface-enhanced Raman scattering (SERS) for biosensing. We focus this review on SERS papers published in the last 10 years and to specific applications of detecting biological analytes. Both intrinsic and extrinsic SERS biosensing schemes have been employed to detect and identify small molecules, nucleic acids, lipids, peptides, and proteins, as well as for in vivo and cellular sensing. Current SERS substrate technologies along with a series of advancements in surface chemistry, sample preparation, intrinsic/extrinsic signal transduction schemes, and tip-enhanced Raman spectroscopy are discussed. The progress covered herein shows great promise for widespread adoption of SERS biosensing. PMID:21509385

Using Laboratory Activities Enhanced with Concept Cartoons to Support Progression in Students' Understanding of Acid-Base Concepts

ERIC Educational Resources Information Center

Ozmen, Haluk; Demircioglu, Gokhan; Burhan, Yasemin; Naseriazar, Akbar; Demircioglu, Hulya

2012-01-01

The aim of this study is to examine the effectiveness of an intervention based on a series of laboratory activities enhanced with concept cartoons. The purpose of the intervention was to enhance students' understanding of acid-base chemistry for eight grade students' from two classes in a Turkish primary school. A pretest-posttest non-equivalent…

Research on radiation characteristics of dipole antenna modulation by sub-wavelength inhomogeneous plasma layer

NASA Astrophysics Data System (ADS)

Kong, Fanrong; Chen, Peiqi; Nie, Qiuyue; Zhang, Xiaoning; Zhang, Zhen; Jiang, Binhao

2018-02-01

The modulation and enhancement effect of sub-wavelength plasma structures on compact antennas exhibits obvious technological advantage and considerable progress. In order to extend the availability of this technology under complex and actual environment with inhomogeneous plasma structure, a numerical simulation analysis based on finite element method has been conducted in this paper. The modulation function of the antenna radiation with sub-wavelength plasma layer located at different positions was investigated, and the inhomogeneous plasma layer with multiple electron density distribution profiles were employed to explore the effect of plasma density distribution on the antenna radiation. It has been revealed that the optical near-field modulated distance and reduced plasma distribution are more beneficial to enhance the radiation. On the basis above, an application-focused research about communication through the plasma sheath surrounding a hypersonic vehicle has been carried out aiming at exploring an effective communication window. The relevant results devote guiding significance in the field of antenna radiation modulation and enhancement, as well as the development of communication technology in hypersonic flight.

Enhanced proton acceleration in an applied longitudinal magnetic field

DOE PAGES

Arefiev, A.; Toncian, T.; Fiksel, G.

2016-10-31

Using two-dimensional particle-in-cell simulations, we examine how an externally applied strong magnetic field impacts proton acceleration in laser-irradiated solid-density targets. We find that a kT-level external magnetic field can sufficiently inhibit transverse transport of hot electrons in a flat laser-irradiated target. While the electron heating by the laser remains mostly unaffected, the reduced electron transport during proton acceleration leads to an enhancement of maximum proton energies and the overall number of energetic protons. The resulting proton beam is much better collimated compared to a beam generated without applying a kT-level magnetic field. A factor of three enhancement of the lasermore » energy conversion efficiency into multi-MeV protons is another effect of the magnetic field. The required kT-level magnetic fields are becoming feasible due to a significant progress that has been made in generating magnetic fields with laser-driven coils using ns-long laser pulses. The possibility of improving characteristics of laser-driven proton beams using such fields is a strong motivation for further development of laser-driven magnetic field capabilities.« less

Enhanced proton acceleration in an applied longitudinal magnetic field

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arefiev, A.; Toncian, T.; Fiksel, G.

Using two-dimensional particle-in-cell simulations, we examine how an externally applied strong magnetic field impacts proton acceleration in laser-irradiated solid-density targets. We find that a kT-level external magnetic field can sufficiently inhibit transverse transport of hot electrons in a flat laser-irradiated target. While the electron heating by the laser remains mostly unaffected, the reduced electron transport during proton acceleration leads to an enhancement of maximum proton energies and the overall number of energetic protons. The resulting proton beam is much better collimated compared to a beam generated without applying a kT-level magnetic field. A factor of three enhancement of the lasermore » energy conversion efficiency into multi-MeV protons is another effect of the magnetic field. The required kT-level magnetic fields are becoming feasible due to a significant progress that has been made in generating magnetic fields with laser-driven coils using ns-long laser pulses. The possibility of improving characteristics of laser-driven proton beams using such fields is a strong motivation for further development of laser-driven magnetic field capabilities.« less

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis

PubMed Central

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi

2011-01-01

Background. In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Methods. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). Results. The urinary protein level in Tg mice decreased significantly during the acute phase (∼Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB. Conclusions. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury. PMID:21525165

Protective effects of L-type fatty acid-binding protein (L-FABP) in proximal tubular cells against glomerular injury in anti-GBM antibody-mediated glomerulonephritis.

PubMed

Kanaguchi, Yasuhiko; Suzuki, Yusuke; Osaki, Ken; Sugaya, Takeshi; Horikoshi, Satoshi; Tomino, Yasuhiko

2011-11-01

In glomerulonephritis (GN), an overload of free fatty acids (FFA) bound to albumin in urinary protein may induce oxidative stress in the proximal tubules. Human liver-type fatty acid-binding protein (hL-FABP) expressed in human proximal tubules, but not rodents, participates in intracellular FFA metabolism and exerts anti-oxidative effects on the progression of tubulointerstitial damage. We examined whether tubular enhancement of this anti-oxidative action modulates the progression of glomerular damage in immune-mediated GN in hL-FABP chromosomal gene transgenic (Tg) mice. Anti-glomerular basement membrane antibody-induced glomerulonephritis (anti-GBM GN) was induced in Tg and wild-type mice (WT). Proteinuria, histopathology, polymorphonuclear (PMN) influx, expression of tubulointerstitial markers for oxidative stress 4-hydroxy-2-Nonenal (HNE) and fibrosis (α-smooth muscle actin), proximal tubular damage (Kim-1), Peroxisome Proliferator-Activated Receptor γ (PPAR γ) and inflammatory cytokines [Monocyte Chemotactic Protein-1, tumor necrosis factor-alpha (TNF-α) and Transforming growth factor beta (TGF-β)] were analyzed. The mice were also treated with an angiotensin type II receptor blocker (ARB). The urinary protein level in Tg mice decreased significantly during the acute phase (~Day 5). Tg mice survived for a significantly longer time than WT mice, with an attenuation of tubulointerstitial damage score and expression of each tubulointerstitial damage marker observed at Day 7. Expression of inflammatory cytokines on Day 7 was higher in WT mice than Tg mice and correlated strongly with PPARγ expression in WT mice, but not in Tg mice. Interestingly, Tg mice showed insufficient PMN influx at 3 and 6 h, with simultaneous elevation of urinary L-FABP and reduction in HNE expression. The two strains of mice showed different types of glomerular damage, with mild mesangial proliferation in Tg mice and severe endothelial swelling with vascular thrombosis in WT mice. The glomerular damage in Tg mice was improved by administration of an ARB. The present experimental model suggests that tubular enhancement of L-FABP may protect mice with anti-GBM GN from progression of both tubulointerstitial and glomerular injury.

BMP and TGFbeta pathways in human central chondrosarcoma: enhanced endoglin and Smad 1 signaling in high grade tumors

PubMed Central

2012-01-01

Background As major regulators of normal chondrogenesis, the bone morphogenic protein (BMP) and transforming growth factor β (TGFB) signaling pathways may be involved in the development and progression of central chondrosarcoma. In order to uncover their possible implication, the aim of this study was to perform a systematic quantitative study of the expression of BMPs, TGFBs and their receptors and to assess activity of the corresponding pathways in central chondrosarcoma. Methods Gene expression analysis was performed by quantitative RT-PCR in 26 central chondrosarcoma and 6 healthy articular cartilage samples. Expression of endoglin and nuclear localization of phosphorylated Smad1/5/8 and Smad2 was assessed by immunohistochemical analysis. Results The expression of TGFB3 and of the activin receptor-like kinase ALK2 was found to be significantly higher in grade III compared to grade I chondrosarcoma. Nuclear phosphorylated Smad1/5/8 and Smad2 were found in all tumors analyzed and the activity of both signaling pathways was confirmed by functional reporter assays in 2 chondrosarcoma cell lines. Immunohistochemical analysis furthermore revealed that phosphorylated Smad1/5/8 and endoglin expression were significantly higher in high-grade compared to low-grade chondrosarcoma and correlated to each other. Conclusions The BMP and TGFβ signaling pathways were found to be active in central chondrosarcoma cells. The correlation of Smad1/5/8 activity to endoglin expression suggests that, as described in other cell types, endoglin could enhance Smad1/5/8 signaling in high-grade chondrosarcoma cells. Endoglin expression coupled to Smad1/5/8 activation could thus represent a functionally important signaling axis for the progression of chondrosarcoma and a regulator of the undifferentiated phenotype of high-grade tumor cells. PMID:23088614

Japanese encephalitis virus replication is negatively regulated by autophagy and occurs on LC3-I- and EDEM1-containing membranes.

PubMed

Sharma, Manish; Bhattacharyya, Sankar; Nain, Minu; Kaur, Manpreet; Sood, Vikas; Gupta, Vishal; Khasa, Renu; Abdin, Malik Z; Vrati, Sudhanshu; Kalia, Manjula

2014-09-01

Autophagy is a lysosomal degradative pathway that has diverse physiological functions and plays crucial roles in several viral infections. Here we examine the role of autophagy in the life cycle of JEV, a neurotropic flavivirus. JEV infection leads to induction of autophagy in several cell types. JEV replication was significantly enhanced in neuronal cells where autophagy was rendered dysfunctional by ATG7 depletion, and in Atg5-deficient mouse embryonic fibroblasts (MEFs), resulting in higher viral titers. Autophagy was functional during early stages of infection however it becomes dysfunctional as infection progressed resulting in accumulation of misfolded proteins. Autophagy-deficient cells were highly susceptible to virus-induced cell death. We also observed JEV replication complexes that are marked by nonstructural protein 1 (NS1) and dsRNA colocalized with endogenous LC3 but not with GFP-LC3. Colocalization of NS1 and LC3 was also observed in Atg5 deficient MEFs, which contain only the nonlipidated form of LC3. Viral replication complexes furthermore show association with a marker of the ER-associated degradation (ERAD) pathway, EDEM1 (ER degradation enhancer, mannosidase α-like 1). Our data suggest that virus replication occurs on ERAD-derived EDEM1 and LC3-I-positive structures referred to as EDEMosomes. While silencing of ERAD regulators EDEM1 and SEL1L suppressed JEV replication, LC3 depletion exerted a profound inhibition with significantly reduced RNA levels and virus titers. Our study suggests that while autophagy is primarily antiviral for JEV and might have implications for disease progression and pathogenesis of JEV, nonlipidated LC3 plays an important autophagy independent function in the virus life cycle.

Nurse and resident satisfaction in magnet long-term care organizations: do high involvement approaches matter?

PubMed

Rondeau, Kent V; Wagar, Terry H

2006-04-01

This study examines the association of high involvement nursing work practices with employer-of-choice (magnet) status in a sample of Canadian nursing homes. In response to a severe shortage of registered nursing personnel, it is imperative for health care organizations to more effectively recruit and retain nursing personnel. Some long-term care organizations are developing employee-centred cultures that allow them to effectively enhance nurse and resident satisfaction. At the same time, many nursing homes have adopted progressive nursing workplace practices (high involvement work practices) that emphasize greater employee empowerment, participation and commitment. A mail survey was sent to the director of nursing in 300 nursing homes in western Canada. In total, 125 useable questionnaires were returned and constituted the data set for this study. Separate ordinary least squares regressions are performed with magnet strength, nurse satisfaction and resident satisfaction used as dependent variables. Nursing homes that demonstrate strong magnet (employer-of-choice) characteristics are more likely to have higher levels of nurse and patient satisfaction, even after controlling for a number of significant factors at the establishment level. Magnet nursing homes are more likely to have progressive participatory decision-making cultures and much more likely to spend considerable resources on job-related training for their nursing staff. The presence of high involvement work practices is not found to be a significant predictor in magnet strength, nurse or resident satisfaction. Merely adopting more high involvement nursing work practices may be insufficient for nursing homes, which desire to become 'employers-of-choice' in their marketplaces, especially if these practices are adopted without a concomitant investment in nurse training or an enhanced commitment to establishing a more democratic and participatory decision-making style involving all nursing staff.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

PubMed

Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Development of mannose functionalized dendrimeric nanoparticles for targeted delivery to macrophages: use of this platform to modulate atherosclerosis.

PubMed

He, Hongliang; Yuan, Quan; Bie, Jinghua; Wallace, Ryan L; Yannie, Paul J; Wang, Jing; Lancina, Michael G; Zolotarskaya, Olga Yu; Korzun, William; Yang, Hu; Ghosh, Shobha

2018-03-01

Dysfunctional macrophages underlie the development of several diseases including atherosclerosis where accumulation of cholesteryl esters and persistent inflammation are 2 of the critical macrophage processes that regulate the progression as well as stability of atherosclerotic plaques. Ligand-dependent activation of liver-x-receptor (LXR) not only enhances mobilization of stored cholesteryl ester but also exerts anti-inflammatory effects mediated via trans-repression of proinflammatory transcription factor nuclear factor kappa B. However, increased hepatic lipogenesis by systemic administration of LXR ligands (LXR-L) has precluded their therapeutic use. The objective of the present study was to devise a strategy to selectively deliver LXR-L to atherosclerotic plaque-associated macrophages while limiting hepatic uptake. Mannose-functionalized dendrimeric nanoparticles (mDNP) were synthesized to facilitate active uptake via the mannose receptor expressed exclusively by macrophages using polyamidoamine dendrimer. Terminal amine groups were used to conjugate mannose and LXR-L T091317 via polyethylene glycol spacers. mDNP-LXR-L was effectively taken up by macrophages (and not by hepatocytes), increased expression of LXR target genes (ABCA1/ABCG1), and enhanced cholesterol efflux. When administered intravenously to LDLR-/- mice with established plaques, significant accumulation of fluorescently labeled mDNP-LXR-L was seen in atherosclerotic plaque-associated macrophages. Four weekly injections of mDNP-LXR-L led to significant reduction in atherosclerotic plaque progression, plaque necrosis, and plaque inflammation as assessed by expression of nuclear factor kappa B target gene matrix metalloproteinase 9; no increase in hepatic lipogenic genes or plasma lipids was observed. These studies validate the development of a macrophage-specific delivery platform for the delivery of anti-atherosclerotic agents directly to the plaque-associated macrophages to attenuate plaque burden. Copyright © 2017 Elsevier Inc. All rights reserved.

Axed MUC4 (MUC4/X) aggravates pancreatic malignant phenotype by activating integrin-β1/FAK/ERK pathway.

PubMed

Jahan, Rahat; Macha, Muzafar A; Rachagani, Satyanarayana; Das, Srustidhar; Smith, Lynette M; Kaur, Sukhwinder; Batra, Surinder K

2018-08-01

Alternative splicing is evolving as an eminent player of oncogenic signaling for tumor development and progression. Mucin 4 (MUC4), a type I membrane-bound mucin, is differentially expressed in pancreatic cancer (PC) and plays a critical role in its progression and metastasis. However, the molecular implications of MUC4 splice variants during disease pathogenesis remain obscure. The present study delineates the pathological and molecular significance of a unique splice variant of MUC4, MUC4/X, which lacks the largest exon 2, along with exon 3. Exon 2 encodes for the highly glycosylated tandem repeat (TR) domain of MUC4 and its absence creates MUC4/X, which is devoid of TR. Expression analysis from PC clinical samples revealed significant upregulation of MUC4/X in PC tissues with most differential expression in poorly differentiated tumors. In vitro studies suggest that overexpression of MUC4/X in wild-type-MUC4 (WT-MUC4) null PC cell lines markedly enhanced PC cell proliferation, invasion, and adhesion to extracellular matrix (ECM) proteins. Furthermore, MUC4/X overexpression leads to an increase in the tumorigenic potential of PC cells in orthotopic transplantation studies. In line with these findings, doxycycline-induced expression of MUC4/X in an endogenous WT-MUC4 expressing PC cell line (Capan-1) also displayed enhanced cell proliferation, invasion, and adhesion to ECM, compared to WT-MUC4 alone, emphasizing its direct involvement in the aggressive behavior of PC cells. Investigation into the molecular mechanism suggested that MUC4/X facilitated PC tumorigenesis via integrin-β1/FAK/ERK signaling pathway. Overall, these findings revealed the novel role of MUC4/X in promoting and sustaining the oncogenic features of PC. Copyright © 2018 Elsevier B.V. All rights reserved.

Progressing Toward a Cohesive Pediatric 18F-FDG PET/MR Protocol: Is Administration of Gadolinium Chelates Necessary?

PubMed

Klenk, Christopher; Gawande, Rakhee; Tran, Vy Thao; Leung, Jennifer Trinh; Chi, Kevin; Owen, Daniel; Luna-Fineman, Sandra; Sakamoto, Kathleen M; McMillan, Alex; Quon, Andy; Daldrup-Link, Heike E

2016-01-01

With the increasing availability of integrated PET/MR scanners, the utility and need for MR contrast agents for combined scans is questioned. The purpose of our study was to evaluate whether administration of gadolinium chelates is necessary for evaluation of pediatric tumors on (18)F-FDG PET/MR images. First, in 119 pediatric patients with primary and secondary tumors, we used 14 diagnostic criteria to compare the accuracy of several MR sequences: unenhanced T2-weighted fast spin-echo imaging; unenhanced diffusion-weighted imaging; and-before and after gadolinium chelate contrast enhancement-T1-weighted 3-dimensional spoiled gradient echo LAVA (liver acquisition with volume acquisition) imaging. Next, in a subset of 36 patients who had undergone (18)F-FDG PET within 3 wk of MRI, we fused the PET images with the unenhanced T2-weighted MR images (unenhanced (18)F-FDG PET/MRI) and the enhanced T1-weighted MR images (enhanced (18)F-FDG PET/MRI). Using the McNemar test, we compared the accuracy of the two types of fused images using the 14 diagnostic criteria. We also evaluated the concordance between (18)F-FDG avidity and gadolinium chelate enhancement. The standard of reference was histopathologic results, surgical notes, and follow-up imaging. There was no significant difference in diagnostic accuracy between the unenhanced and enhanced MR images. Accordingly, there was no significant difference in diagnostic accuracy between the unenhanced and enhanced (18)F-FDG PET/MR images. (18)F-FDG avidity and gadolinium chelate enhancement were concordant in 30 of the 36 patients and 106 of their 123 tumors. Gadolinium chelate administration is not necessary for accurate diagnostic characterization of most solid pediatric malignancies on (18)F-FDG PET/MR images, with the possible exception of focal liver lesions. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma

PubMed Central

Barbaro, Barbara; Illi, Barbara; Nasi, Sergio; Martini, Maurizio; Licata, Anna; Miele, Luca; Grieco, Antonio; Balsano, Clara

2018-01-01

Free serum copper correlates with tumor incidence and progression of human cancers, including hepatocellular carcinoma (HCC). Copper extracellular uptake is provided by the transporter CTR1, whose expression is regulated to avoid excessive intracellular copper entry. Inadequate copper serum concentration is involved in the pathogenesis of Non Alcoholic Fatty Liver Disease (NAFLD), which is becoming a major cause of liver damage progression and HCC incidence. Finally, MYC is over-expressed in most of HCCs and is a critical regulator of cellular growth, tumor invasion and metastasis. The purpose of our study was to understand if higher serum copper concentrations might be involved in the progression of NAFLD-cirrhosis toward-HCC. We investigated whether high exogenous copper levels sensitize liver cells to transformation and if it exists an interplay between copper-related proteins and MYC oncogene. NAFLD-cirrhotic patients were characterized by a statistical significant enhancement of serum copper levels, even more evident in HCC patients. We demonstrated that high extracellular copper concentrations increase cell growth, migration, and invasion of liver cancer cells by modulating MYC/CTR1 axis. We highlighted that MYC binds a specific region of the CTR1 promoter, regulating its transcription. Accordingly, CTR1 and MYC proteins expression were progressively up-regulated in liver tissues from NAFLD-cirrhotic to HCC patients. This work provides novel insights on the molecular mechanisms by which copper may favor the progression from cirrhosis to cancer. The Cu/MYC/CTR1 interplay opens a window to refine HCC diagnosis and design new combined therapies. PMID:29507693

Dietary restriction slightly affects glucose homeostasis and delays plasma cholesterol removal in rabbits with dietary lipid lowering.

PubMed

Yu, Qi; Liu, Ruihan; Han, Lijuan; Zhang, Guangwei; Guan, Hua; Pan, Qi; Wang, Siwang; Liu, Enqi

2018-04-15

Dietary restriction (DR) has been reported to promote the beneficial effects on atherosclerotic progression, lipid and glucose metabolism, but little is known about these effects can be enhanced or weakened by dietary lipid lowering. After 12 weeks of the high-cholesterol diet (HCD) feeding, hypercholesterolemic rabbits were fed with either a chow diet ad libitum (AL) or a chow diet with DR for 16 weeks of dietary lipid lowering. Here, we found the DR group exhibited a loss in body weight, small internal organs and the reduced fat mass, but the AL group accumulated more subcutaneous fat than the baseline group. DR treatment slightly worsened glucose tolerance but enhanced insulin sensitivity, and a slight effect of DR on insulin secretion was also observed. After diet cholesterol withdrawal, rabbits showed persistently lowering of total cholesterol and triglyceride in plasma. The DR group had significantly higher plasma total cholesterol than the AL group at the most time points during 7 to 16 weeks of lipid lowering. Although both AL and DR groups developed more severe atherosclerosis than baseline group, DR did not improve atherosclerotic progression and the accumulation of macrophages and smooth muscle cells as well. We concluded that DR affected glucose and lipid metabolism but did not ameliorate atherosclerosis in rabbits when associated with lipid lowering by the dietary cholesterol withdrawal.

Adrenic acid as an inflammation enhancer in non-alcoholic fatty liver disease.

PubMed

Horas H Nababan, Saut; Nishiumi, Shin; Kawano, Yuki; Kobayashi, Takashi; Yoshida, Masaru; Azuma, Takeshi

2017-06-01

This study was designed to identify novel links between lipid species and disease progression in non-alcoholic fatty liver disease (NAFLD). We analyzed lipid species in the liver and plasma of db/db mice fed a choline-deficient l-amino acid-defined, high-fat diet (CDAHFD) using liquid chromatography/mass spectrometry (LC/MS). An in vitro experiment was performed using HepG2 cells stimulated with recombinant human TNFα or IL1β. The expression of steatosis-, inflammation-, and fibrosis-related genes were analyzed. Plasma samples from NAFLD patients were also analyzed by LC/MS. The CDAHFD-fed db/db mice with hepatic steatosis, inflammation, mild fibrosis, obesity, and hypercholesterolemia displayed significantly higher hepatic and plasma levels of free adrenic acid (p < 0.05). The accumulated adrenic acid in the CDAHFD-fed db/db mice was associated with increased expression of ELOVL2 and 5, and the suppression of the acyl-CoA oxidase 1 gene during peroxisomal β-oxidation. The pretreatment of HepG2 cells with adrenic acid enhanced their cytokine-induced cytokines and chemokines mRNA expression. In NAFLD patients, the group with the highest ALT levels exhibited higher plasma adrenic acid concentrations than the other ALT groups (p-value for trend <0.001). Data obtained demonstrated that adrenic acid accumulation contributes to disease progression in NAFLD. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of virtual learning environment (VLE): A technological approach to genetics teaching on high school students' content knowledge, self-efficacy and career goal aspirations

NASA Astrophysics Data System (ADS)

Kandi, Kamala M.

This study examines the effect of a technology-based instructional tool 'Geniverse' on the content knowledge gains, Science Self-Efficacy, Technology Self-Efficacy, and Career Goal Aspirations among 283 high school learners. The study was conducted in four urban high schools, two of which have achieved Adequate Yearly Progress (AYP) and two have not. Students in both types of schools were taught genetics either through Geniverse, a virtual learning environment or Dragon genetics, a paper-pencil activity embedded in traditional instructional method. Results indicated that students in all schools increased their knowledge of genetics using either type of instructional approach. Students who were taught using Geniverse demonstrated an advantage for genetics knowledge although the effect was small. These increases were more pronounced in the schools that had been meeting the AYP goal. The other significant effect for Geniverse was that students in the technology-enhanced classrooms increased in science Self-Efficacy while students in the non-technology enhanced classrooms decreased. In addition, students from Non-AYP schools showed an improvement in Science and Technology Self-Efficacy; however the effects were small. The implications of these results for the future use of technology-enriched classrooms were discussed. Keywords: Technology-based instruction, Self-Efficacy, career goals and Adequate Yearly Progress (AYP).

APPL1-Mediating Leptin Signaling Contributes to Proliferation and Migration of Cancer Cells.

PubMed

Ding, Youming; Cao, Yingkang; Wang, Bin; Wang, Lei; Zhang, Yemin; Zhang, Deling; Chen, Xiaoyan; Li, Mingxin; Wang, Changhua

2016-01-01

Leptin has been implicated in tumorigenesis and tumor progression, particularly in obese patients. As a multifunctional adaptor protein, APPL1 (containing pleckstrin homology domain, phosphotyrosine binding domain, and a leucine zipper motif 1) plays a critical role in regulating adiponectin and insulin signaling pathways. Currently, high APPL1 level has been suggested to be related to metastases and progression of some types of cancer. However, the intercourse between leptin signaling pathway and APPL1 remains poorly understood. Here, we show that the protein levels and phosphorylation statues of APPL1were highly expressed in tissues from human hepatocellular carcinoma and triple-positive breast cancer. Leptin stimulated APPL1 phosphorylation in a time-dependent manner in both human hepatocellular carcinoma HepG2 cell and breast cancer MCF-7 cell. Overexpression or suppression of APPL1 promoted or attenuated, respectively, leptin-induced phosphorylation of STAT3, ERK1/2, and Akt in the cancer cells, accompanied with enhanced or mitigated cell proliferation and migration. In addition, we identified that APPL1 directly bound to both leptin receptor and STAT3. This interaction was significantly enhanced by leptin stimulation. Our results suggested that APPL1 positively mediated leptin signaling and promoted leptin-induced proliferation and migration of cancer cells. This finding reveals a novel mechanism by which leptin promotes the motility and growth of cancer cells.

Morphine affects HIV-induced inflammatory response without influencing viral replication in human monocyte-derived macrophages

PubMed Central

Dave, Rajnish S.

2011-01-01

Opiate-abusing individuals are in the top three risk-factor groups for HIV infection. In fact, almost 30% of HIV-infected individuals in the USA are reported to abuse opiates, highlighting the intersection of drugs of abuse with HIV/AIDS. Opiate-abusers are cognitively impaired and suffer from neurological dysfunctions that may lead to high-risk sexual behavior, poor adherence to antiretroviral regimens, and hepatitis-C virus infection. Collectively, these factors may contribute to accelerated HIV CNS disease progression. To understand the role of morphine in disease progression, we sought to determine whether morphine influences HIV-induced inflammation or viral replication in human monocyte-derived macrophages (h-mdms) and MAGI cells infected with HIV and exposed to morphine. Chronic morphine exposure of HIV-infected h-mdms led to significant alterations in secretion of IL-6 and MCP-2. Morphine enhanced IL-6 secretion and blunted MCP-2 secretion from HIV-infected h-mdms. However, exposure of HIV-infected h-mdms to morphine had no effect on TNF-α secretion. Morphine had no effect on later-stages of viral replication in HIV-infected h-mdms. Morphine had a potentially additive effect on the HIV-induced production of IL-6 and delayed HIV-induced MCP-2 production. These results suggest that in HIV-infected opiate abusers enhanced CNS inflammation might result even when HIV disease is controlled. PMID:22066570

Pokemon enhances proliferation, cell cycle progression and anti-apoptosis activity of colorectal cancer independently of p14ARF-MDM2-p53 pathway.

PubMed

Zhao, Yi; Yao, Yun-hong; Li, Li; An, Wei-fang; Chen, Hong-zen; Sun, Li-ping; Kang, Hai-xian; Wang, Sen; Hu, Xin-rong

2014-12-01

Pokemon has been showed to directly suppress p14(ARF) expression and also to overexpress in multiple cancers. However, p14(ARF)-MDM2-p53 pathway is usually aberrant in colorectal cancer (CRC). The aim is to confirm whether Pokemon plays a role in CRC and explore whether Pokemon works through p14(ARF)-MDM2-p53 pathway in CRC. Immunohistochemistry for Pokemon, p14(ARF) and Mtp53 protein was applied to 45 colorectal epitheliums (CREs), 42 colorectal adenomas (CRAs) and 66 CRCs. Pokemon was knocked down with RNAi technique in CRC cell line Lovo to detect mRNA expression of p14(ARF) with qRT-PCR, cell proliferation with CCK8 assay, and cell cycle and apoptosis with flowcytometry analysis. The protein expression rates were significantly higher in CRC (75.8%) than in CRE (22.2 %) or CRA (38.1%) for Pokemon and higher in CRC (53.0%) than in CRE (0) or CRA (4.8%) for Mtp53, but not significantly different in CRC (86.4 %) versus CRE (93.3%) or CRA (90.5 %) for p14(ARF). Higher expression rate of Pokemon was associated with lymph node metastasis and higher Duke's stage. After knockdown of Pokemon in Lovo cells, the mRNA level of p14(ARF) was not significantly changed, the cell proliferation ability was decreased by 20.6%, cell cycle was arrested by 55.7% in G0/G1 phase, and apoptosis rate was increased by 19.0%. Pokemon enhanced the oncogenesis of CRC by promoting proliferation, cell cycle progression and anti-apoptosis activity of CRC cells independently of p14(ARF)-MDM2-p53 pathway. This finding provided a novel idea for understanding and further studying the molecular mechanism of Pokemon on carcinogenesis of CRC.

Dynamic contrast-enhanced perfusion area-detector CT assessed with various mathematical models: Its capability for therapeutic outcome prediction for non-small cell lung cancer patients with chemoradiotherapy as compared with that of FDG-PET/CT.

PubMed

Ohno, Yoshiharu; Fujisawa, Yasuko; Koyama, Hisanobu; Kishida, Yuji; Seki, Shinichiro; Sugihara, Naoki; Yoshikawa, Takeshi

2017-01-01

To directly compare the capability of dynamic first-pass contrast-enhanced (CE-) perfusion area-detector CT (ADCT) and PET/CT for early prediction of treatment response, disease progression and overall survival of non-small cell carcinoma (NSCLC) patients treated with chemoradiotherapy. Fifty-three consecutive Stage IIIB NSCLC patients who had undergone PET/CT, dynamic first-pass CE-perfusion ADCT, chemoradiotherapy, and follow-up examination were enrolled in this study. They were divided into two groups: 1) complete or partial response (CR+PR) and 2) stable or progressive disease (SD+PD). Pulmonary arterial and systemic arterial perfusions and total perfusion were assessed at targeted lesions with the dual-input maximum slope method, permeability surface and distribution volume with the Patlak plot method, tumor perfusion with the single-input maximum slope method, and SUV max , and results were averaged to determine final values for each patient. Next, step-wise regression analysis was used to determine which indices were the most useful for predicting therapeutic effect. Finally, overall survival of responders and non-responders assessed by using the indices that had a significant effect on prediction of therapeutic outcome was statistically compared. The step-wise regression test showed that therapeutic effect (r 2 =0.63, p=0.01) was significantly affected by the following three factors in order of magnitude of impact: systemic arterial perfusion, total perfusion, and SUV max . Mean overall survival showed a significant difference for total perfusion (p=0.003) and systemic arterial perfusion (p=0.04). Dynamic first-pass CE-perfusion ADCT as well as PET/CT are useful for treatment response prediction in NSCLC patients treated with chemoradiotherapy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Role for chondroitin sulfate glycosaminoglycan in NEDD9-mediated breast cancer cell growth.

PubMed

Iida, Joji; Dorchak, Jesse; Clancy, Rebecca; Slavik, Juliana; Ellsworth, Rachel; Katagiri, Yasuhiro; Pugacheva, Elena N; van Kuppevelt, Toin H; Mural, Richard J; Cutler, Mary Lou; Shriver, Craig D

2015-01-15

There are lines of evidence demonstrating that NEDD9 (Cas-L, HEF-1) plays a key role in the development, progression, and metastasis of breast cancer cells. We previously reported that NEDD9 plays a critical role for promoting migration and growth of MDA-MB-231. In order to further characterize the mechanisms of NEDD9-mediated cancer migration and growth, stable cells overexpressing NEDD9 were generated using HCC38 as a parental cell line which expresses low level of endogenous NEDD9. Microarray studies demonstrated that core proteins of CD44 and Serglycin were markedly upregulated in HCC38(NEDD9) cells compared to HCC38(Vector) cells, while those of Syndecan-1, Syndecan-2, and Versican were downregulated in HCC38(NEDD9). Importantly, enzymes generating chondroitin sulfate glycosaminoglycans (CS) such as CHST11, CHST15, and CSGALNACT1 were upregulated in HCC38(NEDD9) compared to HCC38(Vector). Immunofluorescence studies using specific antibody, GD3G7, confirmed the enhanced expression of CS-E subunit in HCC38(NEDD9). Immunoprecipitation and western blotting analysis demonstrated that CS-E was attached to CD44 core protein. We demonstrated that removing CS by chondroitinase ABC significantly inhibited anchorage-independent colony formation of HCC38(NEDD9) in methylcellulose. Importantly, the fact that GD3G7 significantly inhibited colony formation of HCC38(NEDD9) cells suggests that CS-E subunit plays a key role in this process. Furthermore, treatment of HCC38(NEDD9) cells with chondroitinase ABC or GD3G7 significantly inhibited mammosphere formation. Exogenous addition of CS-E enhanced colony formation and mammosphere formation of HCC38 parental and HCC38(Vector) cells. These results suggest that NEDD9 regulates the synthesis and expression of tumor associated glycocalyx structures including CS-E, which plays a key role in promoting and regulating breast cancer progression and metastasis and possibly stem cell phenotypes. Copyright © 2014 Elsevier Inc. All rights reserved.

Selection of an early biomarker for vascular normalization using dynamic contrast-enhanced ultrasonography to predict outcomes of metastatic patients treated with bevacizumab.

PubMed

Lassau, N; Coiffier, B; Kind, M; Vilgrain, V; Lacroix, J; Cuinet, M; Taieb, S; Aziza, R; Sarran, A; Labbe-Devilliers, C; Gallix, B; Lucidarme, O; Ptak, Y; Rocher, L; Caquot, L M; Chagnon, S; Marion, D; Luciani, A; Feutray, S; Uzan-Augui, J; Benatsou, B; Bonastre, J; Koscielny, S

2016-10-01

Dynamic contrast-enhanced ultrasonography (DCE-US) has been used for evaluation of tumor response to antiangiogenic treatments. The objective of this study was to assess the link between DCE-US data obtained during the first week of treatment and subsequent tumor progression. Patients treated with antiangiogenic therapies were included in a multicentric prospective study from 2007 to 2010. DCE-US examinations were available at baseline and at day 7. For each examination, a 3 min perfusion curve was recorded just after injection of a contrast agent. Each perfusion curve was modeled with seven parameters. We analyzed the correlation between criteria measured up to day 7 on freedom from progression (FFP). The impact was assessed globally, according to tumor localization and to type of treatment. The median follow-up was 20 months. The mean transit time (MTT) evaluated at day 7 was the only criterion significantly associated with FFP (P = 0.002). The cut-off point maximizing the difference between FFP curves was 12 s. Patients with at least a 12 s MTT had a better FFP. The results according to tumor type were significantly heterogeneous: the impact of MTT on FFP was more marked for breast cancer (P = 0.004) and for colon cancer (P = 0.025) than for other tumor types. Similarly, the differences in FFP according to MTT at day 7 were marked (P = 0.004) in patients receiving bevacizumab. The MTT evaluated with DCE-US at day 7 is significantly correlated to FFP of patients treated with bevacizumab. This criterion might be linked to vascular normalization. 2007-A00399-44. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Natural history of moderately dilated tubular ascending aorta: implications for determining the optimal imaging interval.

PubMed

Park, Kay-Hyun; Chung, Suryeun; Kim, Dong Jung; Kim, Jun Sung; Lim, Cheong

2017-05-01

For a moderately dilated ascending aorta (diameter 35-54 mm), current guidelines recommend continuous annual or semi-annual examinations with computed tomography or magnetic resonance imaging. However, few data have shown the yield and benefit of such a protocol. This study aimed to investigate the fate of a moderately dilated ascending aorta and thereby determine the adequate imaging interval. In our institutional database, we identified adult patients having an ascending aortic diameter ≥40 mm in contrast-enhanced computed tomography and follow-up imaging(s) after ≥1 year. Of the 509 patients (mean age 67.2 ± 10.4 years) enrolled in the study, the maximal diameter of the ascending aorta was compared between the first and last images. Also, their medical records were reviewed to investigate the associated illness and clinical events. The mean growth rate of the patients with a 40-44 mm ( n  = 321), 45-49 mm ( n  = 142) and ≥50 mm ( n  = 46) ascending aorta was 0.3 ± 0.5, 0.3 ± 0.5 and 0.7 ± 0.9 mm/year, respectively. During the mean interval of 4.3 ± 2.4 years, significant progression (diameter increase by ≥5 mm) occurred in 3.4, 5.6 and 21.7%, respectively. The 3- to 5-year rates of freedom from significant progression were 99.1%-96.5% (40-44 mm) and 97.8%-96.4% (45-49 mm). In multivariate analysis, initial ascending aortic diameter ≥45 mm and aortic valve regurgitation were significantly associated with significant progression. Acute type A aortic dissection occurred in 5 patients (1%), before the maximal diameter of the ascending aorta reached 55 mm or significant progression was observed. For a moderately dilated ascending aorta not exceeding 45 mm in maximal diameter and stable in the first annual follow-up image, a 3- to 4-year interval would be reasonable before subsequent imaging. More frequent imaging may be warranted in patients with aortic valve insufficiency or with an aortic diameter ≥45 mm. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Introducing modern technology to promote transparency in health services.

PubMed

Islam, Mohammad Shafiqul

2015-01-01

Quantitative indicators show that Bangladeshi maternal and child healthcare is progressing satisfactorily. However, healthcare quality is still inadequate. It is hypothesised that modern technology enhances healthcare quality. Therefore, the purpose of this paper is to investigate how modern technology such as electronic record keeping and the internet can contribute to enhancing Bangladeshi healthcare quality. This study also explores how socio-economic and political factors affect the healthcare quality. This paper is based on a qualitative case study involving 68 in-depth interviews with healthcare professionals, elected representatives, local informants and five focus group discussions with healthcare service users to understand technology's effect on health service quality. The study has been conducted in one rural and one urban service organisations to understand how various factors contribute differently to healthcare quality. The findings show that modern technology, such as the internet and electronic devices for record keeping, contribute significantly to enhancing health service transparency, which in turn leads to quality health and family planning services. The findings also show that information and communication technology (ICT) is an effective mechanism for reducing corruption and promoting transparency. However, resource constraints impact adversely on the introduction of technology, which leads to less transparent healthcare. Progress in education and general socio-economic conditions makes it suitable to enhance ICT usage, which could lead to healthcare transparency, but political and bureaucratic factors pose a major challenge to ensure transparency. This paper can be a useful guide for promoting governance and healthcare quality in developing countries including Bangladesh. It analyses the ICT challenges that healthcare staff face when promoting transparent healthcare. This paper provides a deeper understanding of transparency and healthcare quality in an ICT context using empirical data, which has not been explored in Bangladesh. This critical thinking is useful for policy makers and healthcare practitioners for promoting health service quality.

Comparison of Wintertime Ozone Production Associated With Oil and Gas Extraction Activity in Wyoming and Utah

NASA Astrophysics Data System (ADS)

Oltmans, S. J.; Schnell, R. C.; Mefford, T. K.; Neely, R. R., III

2012-12-01

The wintertime cold, reduced sunlight conditions of the mid-latitudes of continental interior locations are normally not considered to be conducive to significant ozone production. Recent observations have shattered this expectation with hourly ozone mixing ratios regularly exceeding 100 ppb measured in January, February and March in the states of Wyoming and Utah in the United States. Maximum daily eight hour average ozone mixing ratios have exceeded 100 ppb, far exceeding the U.S. threshold of 75 ppb. Conditions under which this dramatic ozone production takes place include a mix of high levels of ozone precursors (NOx and VOCs), a very stable and shallow boundary layer, snow cover providing enhanced UV radiation, and air confining terrain features. The high levels of precursors have been tied to oil and gas extraction activities in the affected regions. Under the requisite meteorological conditions where high pressure, low winds, and snow-covered ground are present extremely stable and shallow (~50-200 m) boundary layers persist. The highly reflective snow cover provides enhanced photolysis rates that in February can exceed those in June. For several winters in Utah and Wyoming with large ozone enhancements, the time series of various meteorological (wind, temperature, solar radiation, snow cover) and chemical parameters (ozone and NOx) show a somewhat different progression of high ozone events between the two locations. In the Unitah Basin of Utah high ozone formation conditions are more persistent throughout the winter than in the Pinedale Anticline region of Wyoming. This is likely a function of the differing topography of the two areas. However, for individual events the two sites show a similar progression of rapid ozone formation each day. Sites in both Utah and Wyoming just outside the oil and gas extraction activity areas show little or no enhanced ozone. Winters without the requisite meteorological conditions also do not experience high ozone events.

Alterations in acid-base homeostasis during water immersion in normal man

NASA Technical Reports Server (NTRS)

Epstein, M.; Schneider, N. S.; Vaamonde, C. A.

1974-01-01

The effects of water immersion on renal bicarbonate and acid excretion were assessed in 10 normal male subjects. Immersion resulted in a highly significant progressive increase in the rate of sodium and bicarbonate excretion, and in urine pH. Immersion was also associated with a significant increase in urine P-CO2; this increase presupposes a maintained rate of hydrogen secretion in the distal tubular segment. The rapidity of onset of the bicarbonaturia (2 hrs of immersion) and the concomitant increase in urinary P-CO2 suggest that enhanced bicarbonate excretion of immersion cannot be completely accounted for by immersion-induced suppression of aldosterone, and that the natriuresis and bicarbonaturia of immersion is mediated in part by an increased proximal rejection of sodium and bicarbonate.

Honoring Progress: An Update on the NGA Center Honor States. Volume 1, Issue 1

ERIC Educational Resources Information Center

Shawe, Torrey, Ed.

2006-01-01

This bimonthly newsletter provides information about the progress of the Honor States Grant Program, a governor-led effort to improve college- and work-ready graduation rates. This issue explores science, technology, engineering, and math education (STEM), a priority for governors as they try to enhance workforce competitiveness in a global…

Evaluating Efforts to Enhance Health and Wellbeing in Scottish Secondary Schools

ERIC Educational Resources Information Center

Thorburn, Malcolm

2017-01-01

Curriculum for Excellence in Scotland outlines a policy vision of a more progressive, integrated and holistic form of education; a commitment which contains an obligation for health and well-being (HWB) to be a responsibility of all teachers. A critical policy analysis approach was utilized in order to review school-level progress in different…

The effects of a technology-enhanced, flexible choice science program on achievement, self-efficacy and the scale learner progression mechanism in science

NASA Astrophysics Data System (ADS)

Grace, Lori

A mixed methods comparative case study of two DRG I urban high schools was used to determine the effectiveness of the Flexible Choice Science Program (FCSP) at producing equitable learning outcomes in students. FCSP recognized both 'among and within learner' differences, while allowing the teacher the semblance of a single lesson. Program sequencing, a differentiated technology platform and allowances for student control and creativity, allowed learners to progress from novice to master at their own pace. Results showed that holistic participation in FCSP by School A students led to significant positive learning effects, particularly for low ability learners. Results of this study challenge current educational grouping techniques that have resulted in inequity, by demonstrating that when students group themselves, their success increases by more than 100%. Results of this research also challenge common notion that cognition most defines student potential by demonstrating that student affect most influences learning.

A Summary on Progress in Materials Development for Advanced Lithium-ion Cells for NASA's Exploration Missions

NASA Technical Reports Server (NTRS)

Reid, Concha M.

2011-01-01

Vehicles and stand-alone power systems that enable the next generation of human missions to the moon will require energy storage systems that are safer, lighter, and more compact than current state-of-the-art (SOA) aerospace quality lithium-ion (Li-ion) batteries. NASA is developing advanced Li-ion cells to enable or enhance future human missions to Near Earth Objects, such as asteroids, planets, moons, libration points, and orbiting structures. Advanced, high-performing materials are required to provide component-level performance that can offer the required gains at the integrated cell level. Although there is still a significant amount of work yet to be done, the present state of development activities has resulted in the synthesis of promising materials that approach the ultimate performance goals. This paper on interim progress of the development efforts will present performance of materials and cell components and will elaborate on the challenges of the development activities and proposed strategies to overcome technical issues.

Interleukin-22 promotes aerobic glycolysis associated with tumor progression via targeting hexokinase-2 in human colon cancer cells.

PubMed

Liu, Yulin; Xiang, Fan; Huang, Yongming; Shi, Liang; Hu, Chaojie; Yang, Yiming; Wang, Di; He, Nan; Tao, Kaixiong; Wu, Ke; Wang, Guobin

2017-04-11

Interleukin-22 has been explored extensively in human cancer, but its functions and underlying mechanisms are incompletely understood. Here, we show that aberrant interleukin-22 expression facilitates aerobic glycolysis in colon cancer cells. Elevated interleukin-22 mRNA expression was observed and positively correlated with hexokinase-2 in colon cancer tissues. In vitro, interleukin-22 enhanced glucose consumption and lactate production via targeting hexokinase-2 in colon cancer cells. Moreover, the transcriptional factor c-Myc and signal transducer and activator of transcription 3 were involved in interleukin-22-induced up-regulation of hexokinase-2. We further demonstrated that hexokinase-2 partly accounted for interleukin-22-mediated cellular proliferation in DLD-1 cells. In vivo, our data demonstrated that interleukin-22 significantly promoted tumor growth along with elevated expression of c-Myc and hexokinase-2 in mice. In summary, our findings provide a new perspective on the pro-inflammatory cytokine interleukin-22 in promoting aerobic glycolysis associated with tumor progression in human colon cancer cells.

High-value bioproducts from microalgae: strategies and progress.

PubMed

Liang, Ming-Hua; Zhu, Jianhua; Jiang, Jian-Guo

2018-04-20

Microalgae have been considered as alternative sustainable resources for high-value bioproducts such as lipids (especially triacylglycerides [TAGs]), polyunsaturated fatty acids (PUFAs), and carotenoids, due to their relatively high photosynthetic efficiency, no arable land requirement, and ease of scale-up. It is of great significance to exploit microalgae for the production of high-value bioproducts. How to improve the content or productivity of specific bioproducts has become one of the most urgent challenges. In this review, we will describe high-value bioproducts from microalgae and their biosynthetic pathways (mainly for lipids, PUFAs, and carotenoids). Recent progress and strategies for the enhanced production of bioproducts from microalgae are also described in detail, and these strategies take advantages of optimized cultivation conditions with abiotic stress, chemical stress (addition of metabolic precursors, phytohormones, chemical inhibitors, and chemicals inducing oxidative stress response), and molecular approaches such as metabolic engineering, transcriptional engineering, and gene disruption strategies (mainly RNAi, antisense RNA, miRNA-based knockdown, and CRISPR/Cas9).

Asymmetric Supercapacitor Electrodes and Devices.

PubMed

Choudhary, Nitin; Li, Chao; Moore, Julian; Nagaiah, Narasimha; Zhai, Lei; Jung, Yeonwoong; Thomas, Jayan

2017-06-01

The world is recently witnessing an explosive development of novel electronic and optoelectronic devices that demand more-reliable power sources that combine higher energy density and longer-term durability. Supercapacitors have become one of the most promising energy-storage systems, as they present multifold advantages of high power density, fast charging-discharging, and long cyclic stability. However, the intrinsically low energy density inherent to traditional supercapacitors severely limits their widespread applications, triggering researchers to explore new types of supercapacitors with improved performance. Asymmetric supercapacitors (ASCs) assembled using two dissimilar electrode materials offer a distinct advantage of wide operational voltage window, and thereby significantly enhance the energy density. Recent progress made in the field of ASCs is critically reviewed, with the main focus on an extensive survey of the materials developed for ASC electrodes, as well as covering the progress made in the fabrication of ASC devices over the last few decades. Current challenges and a future outlook of the field of ASCs are also discussed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Relationships between harvest time and wine composition in Vitis vinifera L. cv. Cabernet Sauvignon 1. Grape and wine chemistry.

PubMed

Bindon, Keren; Varela, Cristian; Kennedy, James; Holt, Helen; Herderich, Markus

2013-06-01

The study aimed to quantify the effects of grape maturity on wine alcohol, phenolics, flavour compounds and polysaccharides in Vitis vinifera L. cv Cabernet Sauvignon. Grapes were harvested at juice soluble solids from 20 to 26 °Brix which corresponded to a range of wine ethanol concentrations between 12% and 15.5%. Grape anthocyanin and skin tannin concentration increased as ripening progressed, while seed tannin declined. In the corresponding wines, monomeric anthocyanin and wine tannin concentration increased with harvest date, consistent with an enhanced extraction of skin-derived phenolics. In wines, there was an observed increase in yeast-derived metabolites, including volatile esters, dimethyl sulfide, glycerol and mannoproteins with harvest date. Wine volatiles which were significantly influenced by harvest date were isobutyl methoxypyrazine, C(6) alcohols and hexyl acetate, all of which decreased as ripening progressed. The implications of harvest date for wine composition is discussed in terms of both grape composition and yeast metabolism. Copyright © 2012 Elsevier Ltd. All rights reserved.

Diabetes and Kidney Disease: Role of Oxidative Stress

PubMed Central

Jha, Jay C.; Banal, Claudine; Chow, Bryna S.M.; Cooper, Mark E.

2016-01-01

Abstract Significance: Intrarenal oxidative stress plays a critical role in the initiation and progression of diabetic kidney disease (DKD). Enhanced oxidative stress results from overproduction of reactive oxygen species (ROS) in the context of concomitant, insufficient antioxidant pathways. Renal ROS production in diabetes is predominantly mediated by various NADPH oxidases (NOXs), but a defective antioxidant system as well as mitochondrial dysfunction may also contribute. Recent Advances: Effective agents targeting the source of ROS generation hold the promise to rescue the kidney from oxidative damage and prevent subsequent progression of DKD. Critical Issues and Future Directions: In the present review, we summarize and critically analyze molecular and cellular mechanisms that have been demonstrated to be involved in NOX-induced renal injury in diabetes, with particular focus on the role of increased glomerular injury, the development of albuminuria, and tubulointerstitial fibrosis, as well as mitochondrial dysfunction. Furthermore, novel agents targeting NOX isoforms are discussed. Antioxid. Redox Signal. 25, 657–684. PMID:26906673

Pemetrexed in previously treated non-small-cell lung cancer.

PubMed

Rosell, Rafael; Sanchez, Jose Miguel; Taron, Miquel; Moran, Teresa; Ciuraqui, Beatriz; Canela, Mercedes; Felip, Enriqueta; Massuti, Bartomeu; Camps, Carlos

2004-07-01

Several decades of chemotherapy trials in non-small-cell lung cancer (NSCLC) have clearly shown a survival benefit for chemotherapy over best supportive care. However, only short-lived responses are attained, with an average of four cycles of chemotherapy, before tumor progression is observed. Second-line chemotherapy has been demonstrated to improve outcome, with docetaxel (Taxotere) as the predominant cytotoxic drug. A recent randomized trial in second-line NSCLC indicated that the novel drug pemetrexed (Alimta) attained the same response, time to progression, and survival as docetaxel. This finding ushers in a new age in second-line treatment that can be further invigorated by the addition of targeted agents. Accumulated evidence indicates that overexpression of epidermal growth factor receptor and HER2/neu, which occurs frequently in NSCLC, leads to the deregulation of PI3K and MAPK, activating Akt and enhancing chemoresistance. Future clinical trials in NSCLC will include tailored and multitargeted therapy and pemetrexed represents a significant step forward in this direction.

Prospects and progress of high Tc superconductivity for space applications

NASA Technical Reports Server (NTRS)

Romanofsky, Robert R.; Sokoloski, Marty M.

1991-01-01

Current research in the area of high temperature superconductivity is organized around four key areas: communications and data, sensors and cryogenics, propulsion and power, and space materials technology. Recently, laser ablated YBa2Cu3O(7-x) films on LaAlO3 produced far superior RF characteristics when compared to metallic films on the same substrate. The achievement has enabled a number of unique microwave device applications, such as low insertion loss phase shifters and high-Q filters. Melt texturing and melt-quenched techniques are being used to produce bulk material with optimized magnetic properties. These yttrium-enriched materials possess enhanced flux pinning characteristics and could lead to prototype cryocooler bearings. Significant progress has also occurred in bolometer and current lead technology. Studies were conducted to evaluate the effect of high temperature superconducting materials on the performance and life of high power magnetoplasma-dynamic thrusters. Extended studies were also performed to evaluate the benefit of superconducting magnetic energy storage for LEO space station, lunar, and Mars mission applications.

The EST Model for Predicting Progressive Damage and Failure of Open Hole Bending Specimens

NASA Technical Reports Server (NTRS)

Joseph, Ashith P. K.; Waas, Anthony M.; Pineda, Evan J.

2016-01-01

Progressive damage and failure in open hole composite laminate coupons subjected to flexural loading is modeled using Enhanced Schapery Theory (EST). Previous studies have demonstrated that EST can accurately predict the strength of open hole coupons under remote tensile and compressive loading states. This homogenized modeling approach uses single composite shell elements to represent the entire laminate in the thickness direction and significantly reduces computational cost. Therefore, when delaminations are not of concern or are active in the post-peak regime, the version of EST presented here is a good engineering tool for predicting deformation response. Standard coupon level tests provides all the input data needed for the model and they are interpreted in conjunction with finite element (FE) based simulations. Open hole bending test results of three different IM7/8552 carbon fiber composite layups agree well with EST predictions. The model is able to accurately capture the curvature change and deformation localization in the specimen at and during the post catastrophic load drop event.

Differential expression of antimicrobial peptides in active and latent tuberculosis and its relationship with diabetes mellitus.

PubMed

Gonzalez-Curiel, Irma; Castañeda-Delgado, Julio; Lopez-Lopez, Nallely; Araujo, Zaida; Hernandez-Pando, Rogelio; Gandara-Jasso, Benjamin; Macias-Segura, Noe; Enciso-Moreno, Antonio; Rivas-Santiago, Bruno

2011-08-01

Tuberculosis (TB) is one of the most important infectious diseases, causing 1.8 million deaths annually worldwide. This problem has increased because of the association with human immmunodeficiency virus and diabetes mellitus type 2, mainly in developing countries. In the past few years it has been highlighted the significance of antimicrobial peptides in the immunopathogenesis of TB ex vivo and in experimental models studies. In this study we analyzed the expression of CAMP, DEFA1, DEFB4, and DEFB103A in patients with latent TB and progressive TB with and without comorbidity with diabetes mellitus type 2. Antimicrobial peptide gene expression increased during progressive TB, which could be used as a biomarker for reactivation. By contrast, patients with diabetes mellitus type 2 have lower antimicrobial peptides gene expression, suggesting that the lack of its proper production in these patients contribute to enhance the risk for TB reactivation. Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

Progress in Materials and Component Development for Advanced Lithium-ion Cells for NASA's Exploration Missions

NASA Technical Reports Server (NTRS)

Reid, Concha, M.; Reid, Concha M.

2011-01-01

Vehicles and stand-alone power systems that enable the next generation of human missions to the Moon will require energy storage systems that are safer, lighter, and more compact than current state-of-the- art (SOA) aerospace quality lithium-ion (Li-ion) batteries. NASA is developing advanced Li-ion cells to enable or enhance the power systems for the Altair Lunar Lander, Extravehicular Activities spacesuit, and rovers and portable utility pallets for Lunar Surface Systems. Advanced, high-performing materials are required to provide component-level performance that can offer the required gains at the integrated cell level. Although there is still a significant amount of work yet to be done, the present state of development activities has resulted in the synthesis of promising materials that approach the ultimate performance goals. This report on interim progress of the development efforts will elaborate on the challenges of the development activities, proposed strategies to overcome technical issues, and present performance of materials and cell components.

Isotopic Resonance Hypothesis: Experimental Verification by Escherichia coli Growth Measurements

NASA Astrophysics Data System (ADS)

Xie, Xueshu; Zubarev, Roman A.

2015-03-01

Isotopic composition of reactants affects the rates of chemical and biochemical reactions. As a rule, enrichment of heavy stable isotopes leads to progressively slower reactions. But the recent isotopic resonance hypothesis suggests that the dependence of the reaction rate upon the enrichment degree is not monotonous. Instead, at some ``resonance'' isotopic compositions, the kinetics increases, while at ``off-resonance'' compositions the same reactions progress slower. To test the predictions of this hypothesis for the elements C, H, N and O, we designed a precise (standard error +/-0.05%) experiment that measures the parameters of bacterial growth in minimal media with varying isotopic composition. A number of predicted resonance conditions were tested, with significant enhancements in kinetics discovered at these conditions. The combined statistics extremely strongly supports the validity of the isotopic resonance phenomenon (p << 10-15). This phenomenon has numerous implications for the origin of life studies and astrobiology, and possible applications in agriculture, biotechnology, medicine, chemistry and other areas.

Testing the iron hypothesis in a mouse model of atherosclerosis

PubMed Central

Kautz, Léon; Gabayan, Victoria; Wang, Xuping; Wu, Judy; Onwuzurike, James; Jung, Grace; Qiao, Bo; Lusis, Aldons J.; Ganz, Tomas; Nemeth, Elizabeta

2013-01-01

SUMMARY Hepcidin, the iron-regulatory hormone and acute phase reactant, is proposed to contribute to the pathogenesis of atherosclerosis by promoting iron accumulation in plaque macrophages, leading to increased oxidative stress and inflammation in the plaque (the “iron hypothesis”). Hepcidin and iron may thus represent modifiable risk factors in atherosclerosis. We measured hepcidin expression in Apoe−/− mice with varying diets and ages. To assess the role of macrophage iron in atherosclerosis, we generated Apoe−/− mice with macrophage-specific iron accumulation by introducing the ferroportin ffe mutation. Macrophage iron loading was also enhanced by intravenous iron injection. Contrary to the iron hypothesis, we found that hepatic hepcidin expression was not increased at any stage of the atherosclerosis progression in Apoe−/− or Apoe/ffe mice and the atherosclerotic plaque size was not increased in mice with elevated macrophage iron. Our results strongly argue against any significant role of macrophage iron in atherosclerosis progression in mice. PMID:24316081

Does renal ageing affect survival?

PubMed

Razzaque, M Shawkat

2007-10-01

The effects of ageing on progressive deterioration of renal function, both in human and experimental animals, are described elsewhere, but the effect of renal damage on overall survival and longevity is not yet clearly established. The wild-type animals of various genetic backgrounds, fed with regular diet, overtime develop severe age-associated nephropathy, that include but not limited to inflammatory cell infiltration, glomerulosclerosis, and tubulointerstitial fibrosis. Such renal damage significantly reduces their survival. Reducing renal damage, either by caloric restriction or by suppressing growth hormone (GH)/insulin-like growth factor-1 (IGF-1) activity could significantly enhance the longevity of these animals. Available survival studies using experimental animals clearly suggest that kidney pathology is one of the important non-neoplastic lesions that could affect overall survival, and that restoration of renal function by preventing kidney damage could significantly extend longevity. Careful long-term studies are needed to determine the human relevance of these experimental studies.

76 FR 21914 - Agency Information Collection Activities: Extension of Currently Approved Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-19

... designed to enhance the ability of tribes to respond to violent crimes against Indian women, enhance victim...- Annual Progress Report for the Grants to Indian Tribal Governments Program. The Department of Justice, Office on Violence Against Women (OVW) will be submitting the following information collection request to...

Faculties of Education and Institutional Strategies for Knowledge Mobilization: An Exploratory Study

ERIC Educational Resources Information Center

Sa, Creso M.; Li, Sharon X.; Faubert, Brenton

2011-01-01

The goal to enhance the impacts of academic research in the "real world" resonates with progressive visions of the role of universities in society, and finds support among policy makers who have sought to enhance the "transfer", "translation", "uptake", or "valorization" of research knowledge in…

Tumor p38MAPK signaling enhances breast carcinoma vascularization and growth by promoting expression and deposition of pro-tumorigenic factors.

PubMed

Limoge, Michelle; Safina, Alfiya; Truskinovsky, Alexander M; Aljahdali, Ieman; Zonneville, Justin; Gruevski, Aleksandar; Arteaga, Carlos L; Bakin, Andrei V

2017-09-22

The breast carcinoma microenvironment strikingly influences cancer progression and response to therapy. Various cell types in the carcinoma microenvironment show significant activity of p38 mitogen-activated protein kinase (MAPK), although the role of p38MAPK in breast cancer progression is still poorly understood. The present study examined the contribution of tumor p38MAPK to breast carcinoma microenvironment and metastatic capacity. Inactivation of p38MAPK signaling in metastatic breast carcinoma cells was achieved by forced expression of the kinase-inactive mutant of p38/MAPK14 (a dominant-negative p38, dn-p38). Disruption of tumor p38MAPK signaling reduced growth and metastases of breast carcinoma xenografts. Importantly, dn-p38 markedly decreased tumor blood-vessel density and lumen sizes. Mechanistic studies revealed that p38 controls expression of pro-angiogenic extracellular factors such as matrix protein Fibronectin and cytokines VEGFA, IL8, and HBEGF. Tumor-associated fibroblasts enhanced tumor growth and vasculature as well as increased expression of the pro-angiogenic factors. These effects were blunted by dn-p38. Metadata analysis showed elevated expression of p38 target genes in breast cancers and this was an unfavorable marker of disease recurrence and poor-outcome. Thus, our study demonstrates that tumor p38MAPK signaling promotes breast carcinoma growth, invasive and metastatic capacities. Importantly, p38 enhances carcinoma vascularization by facilitating expression and deposition of pro-angiogenic factors. These results argue that p38MAPK is a valuable target for anticancer therapy affecting tumor vasculature. Anti-p38 drugs may provide new therapeutic strategies against breast cancer, including metastatic disease.

Tumor p38MAPK signaling enhances breast carcinoma vascularization and growth by promoting expression and deposition of pro-tumorigenic factors

PubMed Central

Limoge, Michelle; Safina, Alfiya; Truskinovsky, Alexander M.; Aljahdali, Ieman; Zonneville, Justin; Gruevski, Aleksandar; Arteaga, Carlos L.; Bakin, Andrei V.

2017-01-01

The breast carcinoma microenvironment strikingly influences cancer progression and response to therapy. Various cell types in the carcinoma microenvironment show significant activity of p38 mitogen-activated protein kinase (MAPK), although the role of p38MAPK in breast cancer progression is still poorly understood. The present study examined the contribution of tumor p38MAPK to breast carcinoma microenvironment and metastatic capacity. Inactivation of p38MAPK signaling in metastatic breast carcinoma cells was achieved by forced expression of the kinase-inactive mutant of p38/MAPK14 (a dominant-negative p38, dn-p38). Disruption of tumor p38MAPK signaling reduced growth and metastases of breast carcinoma xenografts. Importantly, dn-p38 markedly decreased tumor blood-vessel density and lumen sizes. Mechanistic studies revealed that p38 controls expression of pro-angiogenic extracellular factors such as matrix protein Fibronectin and cytokines VEGFA, IL8, and HBEGF. Tumor-associated fibroblasts enhanced tumor growth and vasculature as well as increased expression of the pro-angiogenic factors. These effects were blunted by dn-p38. Metadata analysis showed elevated expression of p38 target genes in breast cancers and this was an unfavorable marker of disease recurrence and poor-outcome. Thus, our study demonstrates that tumor p38MAPK signaling promotes breast carcinoma growth, invasive and metastatic capacities. Importantly, p38 enhances carcinoma vascularization by facilitating expression and deposition of pro-angiogenic factors. These results argue that p38MAPK is a valuable target for anticancer therapy affecting tumor vasculature. Anti-p38 drugs may provide new therapeutic strategies against breast cancer, including metastatic disease. PMID:28977919

Enhanced J-protein interaction and compromised protein stability of mtHsp70 variants lead to mitochondrial dysfunction in Parkinson's disease.

PubMed

Goswami, Arvind Vittal; Samaddar, Madhuja; Sinha, Devanjan; Purushotham, Jaya; D'Silva, Patrick

2012-08-01

Parkinson's disease (PD) is the second most prevalent progressive neurological disorder commonly associated with impaired mitochondrial function in dopaminergic neurons. Although familial PD is multifactorial in nature, a recent genetic screen involving PD patients identified two mitochondrial Hsp70 variants (P509S and R126W) that are suggested in PD pathogenesis. However, molecular mechanisms underlying how mtHsp70 PD variants are centrally involved in PD progression is totally elusive. In this article, we provide mechanistic insights into the mitochondrial dysfunction associated with human mtHsp70 PD variants. Biochemically, the R126W variant showed severely compromised protein stability and was found highly susceptible to aggregation at physiological conditions. Strikingly, on the other hand, the P509S variant exhibits significantly enhanced interaction with J-protein cochaperones involved in folding and import machinery, thus altering the overall regulation of chaperone-mediated folding cycle and protein homeostasis. To assess the impact of mtHsp70 PD mutations at the cellular level, we developed yeast as a model system by making analogous mutations in Ssc1 ortholog. Interestingly, PD mutations in yeast (R103W and P486S) exhibit multiple in vivo phenotypes, which are associated with 'mitochondrial dysfunction', including compromised growth, impairment in protein translocation, reduced functional mitochondrial mass, mitochondrial DNA loss, respiratory incompetency and increased susceptibility to oxidative stress. In addition to that, R103W protein is prone to aggregate in vivo due to reduced stability, whereas P486S showed enhanced interaction with J-proteins, thus remarkably recapitulating the cellular defects that are observed in human PD variants. Taken together, our findings provide evidence in favor of direct involvement of mtHsp70 as a susceptibility factor in PD.

Increase in slow-wave vasomotion by hypoxia and ischemia in lowlanders and highlanders.

PubMed

Salvi, Paolo; Faini, Andrea; Castiglioni, Paolo; Brunacci, Fausto; Montaguti, Luca; Severi, Francesca; Gautier, Sylvie; Pretolani, Enzo; Benetos, Athanase; Parati, Gianfranco

2018-06-21

The physiological relevance of slow-wave vasomotion is still unclear, even it has been hypothesized it could be a compensatory mechanism enhancing tissue oxygenation in conditions of reduced oxygen supply. Aim of our study was to explore the effects of hypoxia and ischemia on slow-wave vasomotion in microcirculation. Peripheral oxygen saturation and forearm microcirculation flow (laser-Doppler flowmetry) were recorded at baseline and during post-occlusive reactive hyperemia in the Himalaya region from 8 European lowlanders (6 males; aged 29-39yrs) at 1350, 3400 and 5050m, and from 10 Nepalese male highlanders (aged 21-39yrs) at 3400 and 5050m of altitude. The same measurements were also performed at sea level in 16 healthy volunteers (aged 23-61yrs) during a short-term exposure to normobaric hypoxia. In lowlanders, exposure to progressively higher altitude under baseline flow conditions progressively increased 0.06-0.15Hz vasomotion amplitude [power spectral density % expressed as geometric means (geometric standard deviation) =14.0(3.6) at 1350m; 87.0(2.3) at 3400m and 249.8(3.6) at 5050m, p=0.006 and p<0.001 vs 1350m, respectively]. In highlanders, low frequency vasomotion amplitude was similarly enhanced at different altitudes [power spectral density % =183.4(4.1) at 3400m vs 236.0(3.0) at 5050m, p=0.139]. In both groups at altitude it was further increased after ischemic stimulus (p<0.001). At baseline, acute short lasting normobaric hypoxia did not induce low frequency vasomotion, which was conversely induced by ischemia even under normal oxygenation and barometric pressure. This study offers the demonstration of a significant increase in slow-wave vasomotion under prolonged hypobaric-hypoxia exposure at high altitude, with a further enhancement after ischemia induction.

RES hyperphagocytosis by rats with streptozotocin-induced diabetes mellitus.

PubMed

Cornell, R P

1981-03-01

In contrast to previous studies of neutrophils from diabetic animals and humans in vitro and of macrophages from diabetic humans in vivo, which reported phagocytic depression, reticuloendothelial system (RES) hyperphagocytosis of colloidal carbon was observed in rats at 14 and 28 days after diabetes induction with streptozotocin (STZ). Carbon clearance half times were significantly enhanced to 6.3 +/- 0.79 and 8.1 +/- 1.04 min at 14 and 28 days post-STZ, respectively, compared with the nondiabetic value (12.7 +/- 0.98 min). The severity of uncontrolled STZ-induced diabetes in rats was confirmed by significant hypoinsulinemia, hyperglucagonemia, hyperglycemia, and hyperlipidemia. Although body weights of STZ-diabetic animals declined progressively, liver weights as a percent of body weight increased above the control value at 14 and 28 days post-STZ. In fact, expression of carbon phagocytosis as the corrected phagocytic index, which accounts for changes in liver and spleen weights relative to body weight, eliminated the significant difference between STZ-diabetic and nondiabetic animals. Antibiotic treatment of diabetic rats failed to alter the hyperphagocytosis, implying that a chronic bacterial infection was not the cause of phagocytic stimulation. Daily insulin replacements, but not a single large insulin dose to 14-day post-STZ rats, reversed the enhanced phagocytosis of colloidal carbon.

Using tablet technology and instructional videos to enhance preclinical dental laboratory learning.

PubMed

Gadbury-Amyot, Cynthia C; Purk, John H; Williams, Brian Joseph; Van Ness, Christopher J

2014-02-01

The purpose of this pilot study was to examine if tablet technology with accompanying instructional videos enhanced the teaching and learning outcomes in a preclinical dental laboratory setting. Two procedures deemed most challenging in Operative Dentistry II were chosen for the development of instructional videos. A random sample of thirty students was chosen to participate in the pilot. Comparison of faculty evaluations of the procedures between the experimental (tablet) and control (no tablet) groups resulted in no significant differences; however, there was a trend toward fewer failures in the experimental group. Examination of the ability to accurately self-assess was compared by exploring correlations between faculty and student evaluations. While correlations were stronger in the experimental group, the control group had significant correlations for all three procedures, while the experimental group had significant correlations on only two of the procedures. Students strongly perceived that the tablets and videos helped them perform better and more accurately self-assess their work products. Students did not support requiring that they purchase/obtain a specific brand of technology. As a result of this pilot study, further development of ideal and non-ideal videos are in progress, and the school will be implementing a "Bring Your Own Device" policy with incoming students.

Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells

PubMed Central

Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

2010-01-01

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance. PMID:20237142

Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

PubMed

Fang, Feng; Zheng, Jiamao; Galbaugh, Traci L; Fiorillo, Alyson A; Hjort, Elizabeth E; Zeng, Xianke; Clevenger, Charles V

2010-06-01

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells. CypB knockdown with two independent siRNAs was shown to impair PRL-induced reporter expression in breast cancer cell line. cDNA microarray analysis was performed on these cells to assess the effect of CypB reduction, and revealed a significant decrease in PRL-induced endogenous gene expression in two breast cancer cell lines. Parallel functional assays revealed corresponding alterations of both anchorage-independent cell growth and cell motility of breast cancer cells. Our results demonstrate that CypB expression levels significantly modulate PRL-induced function in breast cancer cells ultimately resulting in enhanced levels of PRL-responsive gene expression, cell growth, and migration. Given the increasingly appreciated role of PRL in the pathogenesis of breast cancer, the actions of CypB detailed here are of biological significance.

Effects of lines of progress and semilogarithmic charts on ratings of charted data

PubMed Central

Bailey, Donald B.

1984-01-01

The extent to which interrater agreement and ratings of significance on both changes in level and trend are affected by lines of progress and semilogarithmic charts was investigated. Thirteen graduate students rated four sets of charts, each set containing 19 phase changes. Set I data were plotted on equal interval charts. In Set II a line of progress was drawn through each phase on each chart. In Set III data points were replotted on semilogarithmic charts. In Set IV a line of progress was drawn through each phase of each Set III chart. A significant main effect on interrater agreement was found for lines of progress as well as a significant 2-way interaction between lines of progress and change type. Three main effects (chart type, lines of progress, and type of change) and a significant 3-way interaction were found for ratings of significance. Implications of these data for visual analysis of charted data are discussed. PMID:16795676

Thin-film thermoelectric devices with high room-temperature figures of merit.

PubMed

Venkatasubramanian, R; Siivola, E; Colpitts, T; O'Quinn, B

2001-10-11

Thermoelectric materials are of interest for applications as heat pumps and power generators. The performance of thermoelectric devices is quantified by a figure of merit, ZT, where Z is a measure of a material's thermoelectric properties and T is the absolute temperature. A material with a figure of merit of around unity was first reported over four decades ago, but since then-despite investigation of various approaches-there has been only modest progress in finding materials with enhanced ZT values at room temperature. Here we report thin-film thermoelectric materials that demonstrate a significant enhancement in ZT at 300 K, compared to state-of-the-art bulk Bi2Te3 alloys. This amounts to a maximum observed factor of approximately 2.4 for our p-type Bi2Te3/Sb2Te3 superlattice devices. The enhancement is achieved by controlling the transport of phonons and electrons in the superlattices. Preliminary devices exhibit significant cooling (32 K at around room temperature) and the potential to pump a heat flux of up to 700 W cm-2; the localized cooling and heating occurs some 23,000 times faster than in bulk devices. We anticipate that the combination of performance, power density and speed achieved in these materials will lead to diverse technological applications: for example, in thermochemistry-on-a-chip, DNA microarrays, fibre-optic switches and microelectrothermal systems.

Antioxidant Drug Tempol Promotes Functional Metabolic Changes in the Gut Microbiota.

PubMed

Cai, Jingwei; Zhang, Limin; Jones, Richard A; Correll, Jared B; Hatzakis, Emmanuel; Smith, Philip B; Gonzalez, Frank J; Patterson, Andrew D

2016-02-05

Recent studies have identified the important role of the gut microbiota in the pathogenesis and progression of obesity and related metabolic disorders. The antioxidant tempol was shown to prevent or reduce weight gain and modulate the gut microbiota community in mice; however, the mechanism by which tempol modulates weight gain/loss with respect to the host and gut microbiota has not been clearly established. Here we show that tempol (0, 1, 10, and 50 mg/kg p.o. for 5 days) decreased cecal bacterial fermentation and increased fecal energy excretion in a dose-dependent manner. Liver (1)H NMR-based metabolomics identified a dose-dependent decrease in glycogen and glucose, enhanced glucogenic and ketogenic activity (tyrosine and phenylalanine), and increased activation of the glycolysis pathway. Serum (1)H NMR-based metabolomics indicated that tempol promotes enhanced glucose catabolism. Hepatic gene expression was significantly altered as demonstrated by an increase in Pepck and G6pase and a decrease in Hnf4a, ChREBP, Fabp1, and Cd36 mRNAs. No significant change in the liver and serum metabolomic profiles was observed in germ-free mice, thus establishing a significant role for the gut microbiota in mediating the beneficial metabolic effects of tempol. These results demonstrate that tempol modulates the gut microbial community and its function, resulting in reduced host energy availability and a significant shift in liver metabolism toward a more catabolic state.

Arterial Perfusion Imaging–Defined Subvolume of Intrahepatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hesheng, E-mail: hesheng@umich.edu; Farjam, Reza; Feng, Mary

2014-05-01

Purpose: To assess whether an increase in a subvolume of intrahepatic tumor with elevated arterial perfusion during radiation therapy (RT) predicts tumor progression after RT. Methods and Materials: Twenty patients with unresectable intrahepatic cancers undergoing RT were enrolled in a prospective, institutional review board–approved study. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was performed before RT (pre-RT), after delivering ∼60% of the planned dose (mid-RT) and 1 month after completion of RT to quantify hepatic arterial perfusion. The arterial perfusions of the tumors at pre-RT were clustered into low-normal and elevated perfusion by a fuzzy clustering-based method, and the tumor subvolumesmore » with elevated arterial perfusion were extracted from the hepatic arterial perfusion images. The percentage changes in the tumor subvolumes and means of arterial perfusion over the tumors from pre-RT to mid-RT were evaluated for predicting tumor progression post-RT. Results: Of the 24 tumors, 6 tumors in 5 patients progressed 5 to 21 months after RT completion. Neither tumor volumes nor means of tumor arterial perfusion at pre-RT were predictive of treatment outcome. The mean arterial perfusion over the tumors increased significantly at mid-RT in progressive tumors compared with the responsive tumors (P=.006). From pre-RT to mid-RT, the responsive tumors had a decrease in the tumor subvolumes with elevated arterial perfusion (median, −14%; range, −75% to 65%), whereas the progressive tumors had an increase of the subvolumes (median, 57%; range, −7% to 165%) (P=.003). Receiver operating characteristic analysis of the percentage change in the subvolume for predicting tumor progression post-RT had an area under the curve of 0.90. Conclusion: The increase in the subvolume of the intrahepatic tumor with elevated arterial perfusion during RT has the potential to be a predictor for tumor progression post-RT. The tumor subvolume could be a radiation boost candidate for response-driven adaptive RT.« less

Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.

PubMed

Yan, Xin-Long; Jia, Ya-Li; Chen, Lin; Zeng, Quan; Zhou, Jun-Nian; Fu, Chun-Jiang; Chen, Hai-Xu; Yuan, Hong-Feng; Li, Zhi-Wei; Shi, Lei; Xu, Ying-Chen; Wang, Jing-Xue; Zhang, Xiao-Mei; He, Li-Juan; Zhai, Chao; Yue, Wen; Pei, Xue-Tao

2013-06-01

Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013). Copyright © 2013 American Association for the Study of Liver Diseases.

CT Imaging Biomarkers Predict Clinical Outcomes After Pancreatic Cancer Surgery

PubMed Central

Zhu, Liang; Shi, Xiaohua; Xue, Huadan; Wu, Huanwen; Chen, Ge; Sun, Hao; He, Yonglan; Jin, Zhengyu; Liang, Zhiyong; Zhang, Zhuoli

2016-01-01

Abstract This study aimed to determine whether changes in contrast-enhanced computed tomography (CT) parameters could predict postsurgery overall and progression-free survival (PFS) in pancreatic cancer patients. Seventy-nine patients with a final pathological diagnosis of pancreatic adenocarcinoma were included in this study from June 2008 to August 2012. Dynamic contrast-enhanced (DCE) CT of tumors was obtained before curative-intent surgery. Absolute enhancement change (AEC) and relative enhancement change (REC) were evaluated on DCE-CT. PFS and overall survival (OS) were compared based on CT enhancement patterns. The markers of fibrogenic alpha-smooth muscle antigen (α-SMA) and periostin in tumor specimens were evaluated by immunohistochemical staining. The χ2 test was performed to determine whether CT enhancement patterns were associated with α-SMA-periostin expression levels (recorded as positive or negative). Lower REC (<0.9) was associated with shorter PFS (HR 0.51, 95% CI: 0.31–0.89) and OS (HR 0.44, 95% CI: 0.25–0.78). The α-SMA and periostin expression level were negatively correlated with REC (both P = 0). Among several CT enhancement parameters, REC was the best predictor of patient postsurgery survival. Low REC was associated with a short progression-free time and poor survival. The pathological studies suggested that REC might be a reflection of cancer fibrogenic potential. PMID:26844495

Hemochromatosis Enhances Tumor Progression via Upregulation of Intracellular Iron in Head and Neck Cancer

PubMed Central

Lenarduzzi, Michelle; Hui, Angela B. Y.; Yue, Shijun; Ito, Emma; Shi, Wei; Williams, Justin; Bruce, Jeff; Sakemura-Nakatsugawa, Noriko; Xu, Wei; Schimmer, Aaron; Liu, Fei-Fei

2013-01-01

Introduction Despite improvements in treatment strategies for head and neck squamous cell carcinoma (HNSCC), outcomes have not significantly improved; highlighting the importance of identifying novel therapeutic approaches to target this disease. To address this challenge, we proceeded to evaluate the role of iron in HNSCC. Experimental Design Expression levels of iron-related genes were evaluated in HNSCC cell lines using quantitative RT-PCR. Cellular phenotypic effects were assessed using viability (MTS), clonogenic survival, BrdU, and tumor formation assays. The prognostic significance of iron-related proteins was determined using immunohistochemistry. Results In a panel of HNSCC cell lines, hemochromatosis (HFE) was one of the most overexpressed genes involved in iron regulation. In vitro knockdown of HFE in HNSCC cell lines significantly decreased hepcidin (HAMP) expression and intracellular iron level. This in turn, resulted in a significant decrease in HNSCC cell viability, clonogenicity, DNA synthesis, and Wnt signalling. These cellular changes were reversed by re-introducing iron back into HNSCC cells after HFE knockdown, indicating that iron was mediating this phenotype. Concordantly, treating HNSCC cells with an iron chelator, ciclopirox olamine (CPX), significantly reduced viability and clonogenic survival. Finally, patients with high HFE expression experienced a reduced survival compared to patients with low HFE expression. Conclusions Our data identify HFE as potentially novel prognostic marker in HNSCC that promotes tumour progression via HAMP and elevated intracellular iron levels, leading to increased cellular proliferation and tumour formation. Hence, these findings suggest that iron chelators might have a therapeutic role in HNSCC management. PMID:23991213

Three dimensional flow field measurements of a 4:1 aspect ratio subsonic jet

NASA Technical Reports Server (NTRS)

Morrison, G. L.; Swan, D. H.

1989-01-01

Flow field measurements for a subsonic rectangular cold air jet with an aspect ratio of 4:1 (12.7 x 50.8 mm) at a Mach number of 0.09 and Re of 100,000 have been carried out using a three-dimensional laser Doppler anemometer system. Mean velocity measurements show that the jet width spreads more rapidly along the minor axis than along the major axis. The outward velocities, however, are not significantly different for the two axes, indicating the presence of enhanced mixing along the minor axis. The jet slowly changes from a rectangular jet to a circular jet as the flow progresses downstream.

Adult Mammalian Neural Stem Cells and Neurogenesis: Five Decades Later

PubMed Central

Bond, Allison M.; Ming, Guo-li; Song, Hongjun

2015-01-01

Summary Adult somatic stem cells in various organs maintain homeostatic tissue regeneration and enhance plasticity. Since its initial discovery five decades ago, investigations of adult neurogenesis and neural stem cells have led to an established and expanding field that has significantly influenced many facets of neuroscience, developmental biology and regenerative medicine. Here we review recent progress and focus on questions related to adult mammalian neural stem cells that also apply to other somatic stem cells. We further discuss emerging topics that are guiding the field toward better understanding adult neural stem cells and ultimately applying these principles to improve human health. PMID:26431181

2016 Earth System Grid Federation Annual Report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Dean N.

The Earth System Grid Federation (ESGF) experienced a major setback in June 2015, when it experienced a security incident that brought all systems to a halt for more than half a year. However, federation developers and management committee members turned the incident into an opportunity to dramatically upgrade the system security and functionality and to develop planning and policy documents to guide ESGF evolution and success. Moreover, despite the incident, ESGF developer working teams continue to make strong and significant progress on various enhancement projects that will help ensure ESGF can meet the needs of the climate community in themore » coming years.« less

The use of nanoparticulates to treat breast cancer.

PubMed

Tang, Xiaomeng; Loc, Welley S; Dong, Cheng; Matters, Gail L; Butler, Peter J; Kester, Mark; Meyers, Craig; Jiang, Yixing; Adair, James H

2017-10-01

Breast cancer is a major ongoing public health issue among women in both developing and developed countries. Significant progress has been made to improve the breast cancer treatment in the past decades. However, the current clinical approaches are invasive, of low specificity and can generate severe side effects. As a rapidly developing field, nanotechnology brings promising opportunities to human cancer diagnosis and treatment. The use of nanoparticulate-based platforms overcomes biological barriers and allows prolonged blood circulation time, simultaneous tumor targeting and enhanced accumulation of drugs in tumors. Currently available and clinically applicable innovative nanoparticulate-based systems for breast cancer nanotherapies are discussed in this review.

AMPED Program Overview

ScienceCinema

Gur, Ilan

2018-01-16

An overview presentation about ARPA-E's AMPED program. AMPED projects seek to develop advanced sensing, control, and power management technologies that redefine the way we think about battery management. Energy storage can significantly improve U.S. energy independence, efficiency, and security by enabling a new generation of electric vehicles. While rapid progress is being made in new battery materials and storage technologies, few innovations have emerged in the management of advanced battery systems. AMPED aims to unlock enormous untapped potential in the performance, safety, and lifetime of today's commercial battery systems exclusively through system-level innovations, and is thus distinct from existing efforts to enhance underlying battery materials and architectures.

Writing academic papers: lost in translation?

PubMed

Grant, Maria J

2011-12-01

The process of writing for publication is a challenging one. It moves us from the spoken and written word into a realm that requires us to provide supporting evidence to develop an argument in a logical and progressive way. In English language journals, as elsewhere, the quality of the written word is a determining factor in the likelihood of a paper being accepted for publication. By reading past issues of a targeted journal, drawing on the expertise of colleagues and responding positively to feedback, it is possible to significantly enhance your prospects of publication. © 2011 The authors. Health Information and Libraries Journal © 2011 Health Libraries Group.

Gene therapy and its implications in Periodontics

PubMed Central

Mahale, Swapna; Dani, Nitin; Ansari, Shumaila S.; Kale, Triveni

2009-01-01

Gene therapy is a field of Biomedicine. With the advent of gene therapy in dentistry, significant progress has been made in the control of periodontal diseases and reconstruction of dento-alveolar apparatus. Implementation in periodontics include: -As a mode of tissue engineering with three approaches: cell, protein-based and gene delivery approach. -Genetic approach to Biofilm Antibiotic Resistance. Future strategies of gene therapy in preventing periodontal diseases: -Enhances host defense mechanism against infection by transfecting host cells with an antimicrobial peptide protein-encoding gene. -Periodontal vaccination. Gene therapy is one of the recent entrants and its applications in the field of periodontics are reviewed in general here. PMID:20376232

Angiogenesis - a crucial step in breast cancer growth, progression and dissemination by Raman imaging

NASA Astrophysics Data System (ADS)

Kopeć, Monika; Abramczyk, Halina

2018-06-01

Combined micro-Raman imaging and AFM imaging are efficient methods for analyzing human tissue due to their high spatial and spectral resolution as well as sensitivity to subtle chemical, structural and topographical changes. The aim of this study was to determine biochemical composition and mechanical topography around blood vessels in the tumor mass of human breast tissue. Significant alterations of the chemical composition and structural architecture around the blood vessel were found compared to the normal breast tissue. A pronounced increase of collagen-fibroblast-glycocalyx network, as well as enhanced lactic acid, and glycogen activity in patients affected by breast cancer were reported.

Reward Sensitivity for a Palatable Food Reward Peaks During Pubertal Developmental in Rats

PubMed Central

Friemel, Chris M.; Spanagel, Rainer; Schneider, Miriam

2010-01-01

Puberty is a critical period for the initiation of drug use and abuse. Because early drug use onset often accounts for a more severe progression of addiction, it is of importance to understand the underlying mechanisms and neurodevelopmental changes during puberty that are contributing to enhanced reward processing in teenagers. The present study investigated the progression of reward sensitivity toward a natural food reward over the whole course of adolescence in male rats (postnatal days 30–90) by monitoring consummatory, motivational behavior and neurobiological correlates of reward. Using a limited-free intake paradigm, consumption of sweetened condensed milk (SCM) was measured repeatedly in adolescent and adult rats. Additionally, early- and mid-pubertal animals were tested in Progressive Ratio responding for SCM and c-fos protein expression in reward-associated brain structures was examined after odor conditioning for SCM. We found a transient increase in SCM consumption and motivational incentive for SCM during puberty. This increased reward sensitivity was most pronounced around mid-puberty. The behavioral findings are paralleled by enhanced c-fos staining in reward-related structures revealing an intensified neuronal response after reward-cue presentation, distinctive for pubertal animals. Taken together, these data indicate an increase in reward sensitivity during adolescence accompanied by enhanced responsiveness of reward-associated brain structures to incentive stimuli, and it seems that both is strongly pronounced around mid-puberty. Therefore, higher reward sensitivity during pubertal maturation might contribute to the enhanced vulnerability of teenagers for the initiation of experimental drug use. PMID:20700386

Utility of late gadolinium enhancement in pediatric cardiac MRI.

PubMed

Etesami, Maryam; Gilkeson, Robert C; Rajiah, Prabhakar

2016-07-01

Late gadolinium enhancement (LGE) cardiac magnetic resonance (MR) imaging sequence is increasingly used in the evaluation of pediatric cardiovascular disorders, and although LGE might be a normal feature at the sites of previous surgeries, it is pathologically seen as a result of extracellular space expansion, either from acute cell damage or chronic scarring or fibrosis. LGE is broadly divided into ischemic and non-ischemic patterns. LGE caused by myocardial infarction occurs in a vascular distribution and always involves the subendocardial portion, progressively involving the outer regions in a waveform pattern. Non-ischemic cardiomyopathies can have a mid-myocardial (either linear or patchy), subepicardial or diffuse subendocardial distribution. Idiopathic dilated cardiomyopathy can have a linear mid-myocardial pattern, while hypertrophic cardiomyopathy can have fine, patchy enhancement in hypertrophied and non-hypertrophied segments as well as right ventricular insertion points. Myocarditis and sarcoidosis have a mid-myocardial or subepicardial pattern of LGE. Fabry disease typically affects the basal inferolateral segment while Danon disease typically spares the septum. Pericarditis is characterized by diffuse or focal pericardial thickening and enhancement. Thrombus, the most common non-neoplastic cardiac mass, is characterized by absence of enhancement in all sequences, while neoplastic masses show at least some contrast enhancement, depending on the pathology. Regardless of the etiology, presence of LGE is associated with a poor prognosis. In this review, we describe the technical modifications required for performing LGE cardiac MR sequence in children, review and illustrate the patterns of LGE in children, and discuss their clinical significance.

Fibrovascular ingrowth into porous polyethylene orbital implants (Medpor) after modified evisceration.

PubMed

Huang, Danping; Xu, Binbin; Yang, Zhiyun; Xu, Bing; Lin, Xiaolei; Yang, Xiaonan; Zhao, Jing

2015-01-01

To evaluate, using MRI, the extent and pattern of fibrovascular ingrowth into Medpor implants after modified evisceration. Contrast T1-weighted images were performed in 21 patients within 1.5- to69-month intervals after modified evisceration with primary Medpor implantation. In 6 patients, the images were obtained separately following 1- and 5-minute delays after contrast administration. No grade I enhancement occurred in these series. Grade II was observed in 2 patients (9.09%), grade III in 8 patients (36.36%), grade IV in 9 patients (40.91%), and grade V in 3 patients (13.64%). Significant correlation existed between the grade of enhancement and the postevisceration interval (r = 0.483, p = 0.023 < 0.05). The images demonstrated an enhancement pattern that started at the unwrapped posterior pole and anterior location of rectus muscles with progressive centripetal vascularization toward the center of the implant. At the early stage of recovery, the fibrous connective tissue was thick in front of Medpor spheres. In the 5-minute delay images of 6 patients, 2 patients failed to exhibit further enhancement; 2 patients exhibited enlarged and homogeneous enhancement; and 2 patients revealed more intense enhancement patterns. The medical ethics committee of Zhongshan Ophthalmic Center approved the study. Fibrovascular ingrowth into Medpor implants was satisfactory after the modified evisceration and correlated with the duration of the implants. The double layers of sclera effectively prevented the implant extrusion and exposure. The authors recommend waiting at least 5 minutes before obtaining MR images after contrast administration.

Effect of Rhythmic Auditory Stimulation on Hemiplegic Gait Patterns.

PubMed

Shin, Yoon-Kyum; Chong, Hyun Ju; Kim, Soo Ji; Cho, Sung-Rae

2015-11-01

The purpose of our study was to investigate the effect of gait training with rhythmic auditory stimulation (RAS) on both kinematic and temporospatial gait patterns in patients with hemiplegia. Eighteen hemiplegic patients diagnosed with either cerebral palsy or stroke participated in this study. All participants underwent the 4-week gait training with RAS. The treatment was performed for 30 minutes per each session, three sessions per week. RAS was provided with rhythmic beats using a chord progression on a keyboard. Kinematic and temporospatial data were collected and analyzed using a three-dimensional motion analysis system. Gait training with RAS significantly improved both proximal and distal joint kinematic patterns in hip adduction, knee flexion, and ankle plantar flexion, enhancing the gait deviation index (GDI) as well as ameliorating temporal asymmetry of the stance and swing phases in patients with hemiplegia. Stroke patients with previous walking experience demonstrated significant kinematic improvement in knee flexion in mid-swing and ankle dorsiflexion in terminal stance. Among stroke patients, subacute patients showed a significantly increased GDI score compared with chronic patients. In addition, household ambulators showed a significant effect on reducing anterior tilt of the pelvis with an enhanced GDI score, while community ambulators significantly increased knee flexion in mid-swing phase and ankle dorsiflexion in terminal stance phase. Gait training with RAS has beneficial effects on both kinematic and temporospatial patterns in patients with hemiplegia, providing not only clinical implications of locomotor rehabilitation with goal-oriented external feedback using RAS but also differential effects according to ambulatory function.

Progress in Application of the Neurosciences to an Understanding of Human Learning: The Challenge of Finding a Middle-Ground Neuroeducational Theory

ERIC Educational Resources Information Center

Anderson, O. Roger

2014-01-01

Modern neuroscientific research has substantially enhanced our understanding of the human brain. However, many challenges remain in developing a strong, brain-based theory of human learning, especially in complex environments such as educational settings. Some of the current issues and challenges in our progress toward developing comprehensive…

Loss of MURC/Cavin-4 induces JNK and MMP-9 activity enhancement in vascular smooth muscle cells and exacerbates abdominal aortic aneurysm.

PubMed

Miyagawa, Kotaro; Ogata, Takehiro; Ueyama, Tomomi; Kasahara, Takeru; Nakanishi, Naohiko; Naito, Daisuke; Taniguchi, Takuya; Hamaoka, Tetsuro; Maruyama, Naoki; Nishi, Masahiro; Kimura, Taizo; Yamada, Hiroyuki; Aoki, Hiroki; Matoba, Satoaki

2017-06-03

Abdominal aortic aneurysm (AAA) is relatively common in elderly patients with atherosclerosis. MURC (muscle-restricted coiled-coil protein)/Cavin-4 modulating the caveolae function of muscle cells is expressed in cardiomyocytes, skeletal muscle cells and smooth muscle cells. Here, we show a novel functional role of MURC/Cavin-4 in vascular smooth muscle cells (VSMCs) and AAA development. Both wild-type (WT) and MURC/Cavin-4 knockout (MURC -/- ) mice subjected to periaortic application of CaCl 2 developed AAAs. Six weeks after CaCl 2 treatment, internal and external aortic diameters were significantly increased in MURC -/- AAAs compared with WT AAAs, which were accompanied by advanced fibrosis in the tunica media of MURC -/- AAAs. The activity of JNK and matrix metalloproteinase (MMP) -2 and -9 were increased in MURC -/- AAAs compared with WT AAAs at 5 days after CaCl 2 treatment. At 6 weeks after CaCl 2 treatment, MURC -/- AAAs exhibited attenuated JNK activity compared with WT AAAs. There was no difference in the activity of MMP-2 or -9 between saline and CaCl 2 treatments. In MURC/Cavin-4-knockdown VSMCs, TNFα-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Furthermore, WT, MURC -/- , apolipoprotein E -/- (ApoE -/- ), and MURC/Cavin-4 and ApoE double-knockout (MURC -/- ApoE -/- ) mice were subjected to angiotensin II (Ang II) infusion. In both ApoE -/- and MURC -/- ApoE -/- mice infused for 4 weeks with Ang II, AAAs were promoted. The internal aortic diameter was significantly increased in Ang II-infused MURC -/- ApoE -/- mice compared with Ang II-infused ApoE -/- mice. In MURC/Cavin-4-knockdown VSMCs, Ang II-induced activity of JNK and MMP-9 was enhanced compared with control VSMCs. Our results suggest that MURC/Cavin-4 in VSMCs modulates AAA progression at the early stage via the activation of JNK and MMP-9. MURC/Cavin-4 is a potential therapeutic target against AAA progression. Copyright © 2017 Elsevier Inc. All rights reserved.

In vivo imaging of the dynamics of different variants of EGFR in glioblastomas.

PubMed

Shah, Khalid

2011-01-01

A number of altered pathways in cancer cells depend on growth factor receptors. The amplification/alteration of the epidermal growth factor receptor (EGFR) has been shown to play a significant role in enhancing tumor burden in a number of tumors, including malignant glioblastomas (GBM). To dissect the role of EGFR expression in tumor progression in mouse models of cancer and ultimately evaluate targeted therapies, it is necessary to visualize the dynamics of EGFR in real time in vivo. Non-invasive imaging based on quantitative and qualitative changes in light emission by fluorescent and bioluminescent markers offers a huge potential to facilitate drug development. Multiple approaches could be used to follow a molecular target or pathway with the fusion of a bioluminescent-fluorescent marker. This unit describes a protocol for simultaneously imaging EGFR activity and progression of GBM in a mouse model. Human glioma cells transduced with lentiviral vectors bearing different combinations of fluorescent and bioluminescent proteins either fused to EGFR or expressed alone can be grown as monolayers and maintained over several passages. The unit begins with a method for transducing glioma cells with lentiviral vectors for stable expression of these fluorescent and bioluminescent markers in vitro, followed by transplantation of engineered glioma cells in mice, and, finally, sequential bioluminescent imaging of EGFR expression and GBM progression in mice. The protocol details characterization of engineered glioma cells in culture, surgical preparation, craniotomy, cell implantation, animal recovery, and imaging procedures to study kinetics of EGFR expression and GBM progression.

Recent Progress on Systems and Synthetic Biology Approaches to Engineer Fungi As Microbial Cell Factories.

PubMed

Amores, Gerardo Ruiz; Guazzaroni, María-Eugenia; Arruda, Letícia Magalhães; Silva-Rocha, Rafael

2016-04-01

Filamentous fungi are remarkable organisms naturally specialized in deconstructing plant biomass and this feature has a tremendous potential for biofuel production from renewable sources. The past decades have been marked by a remarkable progress in the genetic engineering of fungi to generate industry-compatible strains needed for some biotech applications. In this sense, progress in this field has been marked by the utilization of high-throughput techniques to gain deep understanding of the molecular machinery controlling the physiology of these organisms, starting thus the Systems Biology era of fungi. Additionally, genetic engineering has been extensively applied to modify wellcharacterized promoters in order to construct new expression systems with enhanced performance under the conditions of interest. In this review, we discuss some aspects related to significant progress in the understating and engineering of fungi for biotechnological applications, with special focus on the construction of synthetic promoters and circuits in organisms relevant for industry. Different engineering approaches are shown, and their potential and limitations for the construction of complex synthetic circuits in these organisms are examined. Finally, we discuss the impact of engineered promoter architecture in the single-cell behavior of the system, an often-neglected relationship with a tremendous impact in the final performance of the process of interest. We expect to provide here some new directions to drive future research directed to the construction of high-performance, engineered fungal strains working as microbial cell factories.

The Osteogenic Niche Promotes Early-Stage Bone Colonization of Disseminated Breast Cancer Cells

PubMed Central

Wang, Hai; Yu, Cuijuan; Gao, Xia; Welte, Thomas; Muscarella, Aaron M.; Tian, Lin; Zhao, Hong; Zhao, Zhen; Du, Shiyu; Tao, Jianning; Lee, Brendan; Westbrook, Thomas F.; Wong, Stephen T. C.; Jin, Xin; Rosen, Jeffrey M.; Osborne, C. Kent; Zhang, Xiang H.-F.

2014-01-01

Summary Breast cancer bone micrometastases can remain asymptomatic for years before progressing into overt lesions. The biology of this process, including the microenvironment niche and supporting pathways, is unclear. We find that bone micrometastases predominantly reside in a niche that exhibits features of osteogenesis. Niche interactions are mediated by heterotypic adherens junctions (hAJs) involving cancer-derived E-cadherin and osteogenic N-cadherin, the disruption of which abolishes niche-conferred advantages. We further elucidate that hAJ activates the mTOR pathway in cancer cells, which drives the progression from single cells to micrometastases. Human datasets analyses support the roles of AJ and the mTOR pathway in bone colonization. Our study illuminates the initiation of bone colonization, and provides potential therapeutic targets to block progression toward osteolytic metastases. Significance In advanced stages, breast cancer bone metastases are driven by paracrine crosstalk among cancer cells, osteoblasts, and osteoclasts, which constitute a vicious osteolytic cycle. Current therapies targeting this process limit tumor progression, but do not improve patient survival. On the other hand, bone micrometastases may remain indolent for years before activating the vicious cycle, providing a therapeutic opportunity to prevent macrometastases. Here, we show that bone colonization is initiated in a microenvironment niche exhibiting active osteogenesis. Cancer and osteogenic cells form heterotypic adherens junctions, which enhance mTOR activity and drive early-stage bone colonization prior to osteolysis. These results reveal a strong connection between osteogenesis and micrometastasis and suggest potential therapeutic targets to prevent bone macrometastases. PMID:25600338

Effects of DHA-enriched hen egg yolk and L-cysteine supplementation on quality of cryopreserved boar semen

PubMed Central

Chanapiwat, Panida; Kaeoket, Kampon; Tummaruk, Padet

2009-01-01

The objective of the present study was to determine the effects of docosahexaenoic acid (DHA)-enriched hen egg yolks and L-cysteine supplementation on the qualities of the cryopreserved boar semen. A total of 15 ejaculates from 5 Pietrain boars were divided into 4 groups according to the compositions of the freezing extenders used, that is, normal hen egg yolk (group I), DHA-enriched hen egg yolk (group II), normal hen egg yolk with 5 mmol L−1 of cysteine supplementation (group III) and DHA-enriched hen egg yolk with 5 mmol L−1 of cysteine supplementation (group IV). The semen was cryopreserved using controlled rate freezer and was thawed at 50°C for 12 s. Progressive motility, sperm viability, acrosome integrity and functional integrity of sperm plasma membrane of the post-thawed semen were evaluated. The supplementation of L-cysteine in the freezing extender alone (group III) improved progressive motility (P < 0.05), and the supplementation of L-cysteine in combination with DHA-enriched hen egg yolk (group IV) improved both progressive motility (P < 0.05) and acrosome integrity (P < 0.01). The use of DHA-enriched hen egg yolk alone (group II) did not enhance any of the post-thawed semen qualities (P > 0.05). In conclusion, the supplementation of antioxidant L-cysteine alone or in combination with DHA-enriched hen egg yolk significantly improved the post-thawed semen qualities, especially progressive motility and acrosome integrity. PMID:19633681

Effects of DHA-enriched hen egg yolk and L-cysteine supplementation on quality of cryopreserved boar semen.

PubMed

Chanapiwat, Panida; Kaeoket, Kampon; Tummaruk, Padet

2009-09-01

The objective of the present study was to determine the effects of docosahexaenoic acid (DHA)-enriched hen egg yolks and L-cysteine supplementation on the qualities of the cryopreserved boar semen. A total of 15 ejaculates from 5 Pietrain boars were divided into 4 groups according to the compositions of the freezing extenders used, that is, normal hen egg yolk (group I), DHA-enriched hen egg yolk (group II), normal hen egg yolk with 5 mmol L(-1) of cysteine supplementation (group III) and DHA-enriched hen egg yolk with 5 mmol L(-1) of cysteine supplementation (group IV). The semen was cryopreserved using controlled rate freezer and was thawed at 50 degrees C for 12 s. Progressive motility, sperm viability, acrosome integrity and functional integrity of sperm plasma membrane of the post-thawed semen were evaluated. The supplementation of L-cysteine in the freezing extender alone (group III) improved progressive motility (P < 0.05), and the supplementation of L-cysteine in combination with DHA-enriched hen egg yolk (group IV) improved both progressive motility (P < 0.05) and acrosome integrity (P < 0.01). The use of DHA-enriched hen egg yolk alone (group II) did not enhance any of the post-thawed semen qualities (P > 0.05). In conclusion, the supplementation of antioxidant L-cysteine alone or in combination with DHA-enriched hen egg yolk significantly improved the post-thawed semen qualities, especially progressive motility and acrosome integrity.

Genome organization and long-range regulation of gene expression by enhancers

PubMed Central

Smallwood, Andrea; Ren, Bing

2014-01-01

It is now well accepted that cell-type specific gene regulation is under the purview of enhancers. Great strides have been made recently to characterize and identify enhancers both genetically and epigenetically for multiple cell types and species, but efforts have just begun to link enhancers to their target promoters. Mapping these interactions and understanding how the 3D landscape of the genome constrains such interactions is fundamental to our understanding of mammalian gene regulation. Here, we review recent progress in mapping long-range regulatory interactions in mammalian genomes, focusing on transcriptional enhancers and chromatin organization principles. PMID:23465541

Enhancement of carcinogenesis and fatty infiltration in the pancreas in N-nitrosobis(2-oxopropyl)amine-treated hamsters by high-fat diet.

PubMed

Hori, Mika; Kitahashi, Tsukasa; Imai, Toshio; Ishigamori, Rikako; Takasu, Shinji; Mutoh, Michihiro; Sugimura, Takashi; Wakabayashi, Keiji; Takahashi, Mami

2011-11-01

Obesity is associated with increased pancreatic cancer risk, although the mechanisms have yet to be detailed. This study aimed to elucidate promotion of pancreatic cancer by obesity and hyperlipidemia. Six-week-old female Syrian golden hamsters were treated with N-nitrosobis(2-oxopropyl)amine (BOP) and after 1 week were fed a high-fat diet (HFD) or standard diet (STD) for 6 or 17 weeks. Body weight and serum levels of lipids and leptin were significantly higher in the HFD than the STD group at 14 weeks of age. Pancreatic ductal adenocarcinomas developed only in the BOP + HFD group, with an incidence of 67% (P < 0.01) at 14 weeks of age. In addition, the multiplicity was 2-fold greater in the BOP + HFD group than in the BOP + STD group (P < 0.05) at 25 weeks of age. Pancreatic fatty infiltration was increased by BOP treatment and further enhanced by the HFD, correlating with progression of BOP-induced pancreatic ductal adenocarcinoma and up-regulated expression of adipocytokines and cell proliferation-related genes in the pancreas. High-fat diet is shown to increase serum lipid levels and enhance fatty infiltration in the pancreas with abnormal adipocytokine production, which may accelerate and enhance pancreatic cancer.

Immediate detailed feedback to test-enhanced learning: an effective online educational tool.

PubMed

Wojcikowski, Ken; Kirk, Leslie

2013-11-01

Test-enhanced learning has gained popularity because it is an effective way to increase retention of knowledge; provided the student receives the correct answer soon after the test is taken. To determine whether detailed feedback provided to test-enhanced learning questions is an effective online educational tool for improving performance on complex biomedical information exams. A series of online multiple choice tests were developed to test knowledge of biomedical information that students were expected to know after each patient-case. Following submission of the student answers, one cohort (n = 52) received answers only while the following year, a second cohort (n = 51) received the answers with detailed feedback explaining why each answer was correct or incorrect. Students in both groups progressed through the series of online tests with little assessor intervention. Students receiving the answers along with the explanations within their feedback performed significantly better in the final biomedical information exam than those students receiving correct answers only. This pilot study found that the detailed feedback to test-enhanced learning questions is an important online learning tool. The increase in student performance in the complex biomedical information exam in this study suggests that detailed feedback should be investigated not only for increasing knowledge, but also be investigated for its effect on retention and application of knowledge.

Transuranic solid waste management programs. Progress report, July--December 1975

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1976-09-01

Progress is reported for three transuranic solid waste management programs funded at the Los Alamos Scientific Laboratory (LASL) by the Energy Research and Development Administration (ERDA) Division of Fuel Cycle and Production (NFCP). Under the Transuranic Waste Research and Development Program, continued studies have shown the potential attractiveness of fiber drums as an acceptable substitute for the current mild steel storage containers. Various fire retardants have been evaluated, with one indicating significant ability to inhibit fire propagation. Continued radiolysis studies, under laboratory and field conditions, continue to reaffirm earlier LASL results indicating no significant hazard from radiolytic reactions, assuming nomore » change in current allowable loadings. Care must be exercised to differentiate between radiolytic and chemical reactions. Other efforts have identified a modification of chemical processing to reduce the amounts of plutonium requiring retrievable storage. Studies are also in progress to enhance the sensitivity of the LASL MEGAS assay system. The Transuranic-Contaminated Solid Waste Treatment Development Facility building was 72 percent complete as of December 31, 1975, which is in accord with the existing schedule. Procurement of process components is also on schedule. Certain modifications to the facility have been made, and various pre-facility experiments on waste container handling and processing have been completed. The program for the Evaluation of Transuranic-Contaminated Radioactive Waste Disposal Areas continued development of various computer modules for simulation of radionuclide transport within the biosphere. In addition, program staff contributed to an ERDA document on radioactive waste management through the preparation of a report on burial of radioactive waste at ERDA-contractor and commercial sites.« less

Live Births from Domestic Dog (Canis familiaris) Embryos Produced by In Vitro Fertilization

PubMed Central

Nagashima, Jennifer B.; Sylvester, Skylar R.; Nelson, Jacquelyn L.; Cheong, Soon Hon; Mukai, Chinatsu; Lambo, Colleen; Flanders, James A.; Meyers-Wallen, Vicki N.; Songsasen, Nucharin; Travis, Alexander J.

2015-01-01

Development of assisted reproductive technologies (ART) in the dog has resisted progress for decades, due to their unique reproductive physiology. This lack of progress is remarkable given the critical role ART could play in conserving endangered canid species or eradicating heritable disease through gene-editing technologies—an approach that would also advance the dog as a biomedical model. Over 350 heritable disorders/traits in dogs are homologous with human conditions, almost twice the number of any other species. Here we report the first live births from in vitro fertilized embryos in the dog. Adding to the practical significance, these embryos had also been cryopreserved. Changes in handling of both gametes enabled this progress. The medium previously used to capacitate sperm excluded magnesium because it delayed spontaneous acrosome exocytosis. We found that magnesium significantly enhanced sperm hyperactivation and ability to undergo physiologically-induced acrosome exocytosis, two functions essential to fertilize an egg. Unlike other mammals, dogs ovulate a primary oocyte, which reaches metaphase II on Days 4–5 after the luteinizing hormone (LH) surge. We found that only on Day 6 are oocytes consistently able to be fertilized. In vitro fertilization of Day 6 oocytes with sperm capacitated in medium supplemented with magnesium resulted in high rates of embryo development (78.8%, n = 146). Intra-oviductal transfer of nineteen cryopreserved, in vitro fertilization (IVF)-derived embryos resulted in seven live, healthy puppies. Development of IVF enables modern genetic approaches to be applied more efficiently in dogs, and for gamete rescue to conserve endangered canid species. PMID:26650234

Reprogramming Enhancers to Drive Metastasis.

PubMed

Mostoslavsky, Raul; Bardeesy, Nabeel

2017-08-24

Acquired molecular changes can promote the spreading of primary tumor cells to distant tissues. In this issue of Cell, Roe et al. show that metastatic progression of pancreatic cancer involves large-scale enhancer reprogramming by Foxa1, which activates transcriptional program specifying early endodermal stem cells. Copyright © 2017 Elsevier Inc. All rights reserved.

A 2-Year Progress Report of the AACAP-Harvard Macy Teaching Scholars Program

ERIC Educational Resources Information Center

Hunt, Jeffrey; Stubbe, Dorothy E.; Hanson, Mark; Al-Mateen, Cheryl S.; Cuccio, Anne; Dingle, Arden D.; Glowinski, Anne; Guthrie, Elizabeth; Kelley, Kathy; Malloy, Erin M.; Mehlinger, Renee; O'Melia, Anne; Shatkin, Jess; Anders, Thomas F.

2008-01-01

Objective: The American Academy of Child and Adolescent Psychiatry (AACAP) has partnered with the Harvard Macy Program for Healthcare Educators so that selected child and adolescent psychiatry academic faculty might enhance their teaching expertise in order to possibly enhance recruitment of medical students into child and adolescent psychiatry.…

Blended Learning Environments: Using Social Networking Sites to Enhance the First Year Experience

ERIC Educational Resources Information Center

McCarthy, Joshua

2010-01-01

This study explores blending virtual and physical learning environments to enhance the experience of first year by immersing students into university culture through social and academic interaction between peers. It reports on the progress made from 2008 to 2009 using an existing academic platform, the first year design elective course…

Solid-state optical refrigeration to sub-100 Kelvin regime

DOE Office of Scientific and Technical Information (OSTI.GOV)

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Solid-state optical refrigeration to sub-100 Kelvin regime

DOE PAGES

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; ...

2016-02-05

We report that since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈91K from room temperature.

Solid-state optical refrigeration to sub-100 Kelvin regime

PubMed Central

Melgaard, Seth D.; Albrecht, Alexander R.; Hehlen, Markus P.; Sheik-Bahae, Mansoor

2016-01-01

Since the first demonstration of net cooling twenty years ago, optical refrigeration of solids has progressed to outperform all other solid-state cooling processes. It has become the first and only solid-state refrigerator capable of reaching cryogenic temperatures, and now the first solid-state cooling below 100 K. Such substantial progress required a multi-disciplinary approach of pump laser absorption enhancement, material characterization and purification, and thermal management. Here we present the culmination of two decades of progress, the record cooling to ≈ 91 K from room temperature. PMID:26847703

Marvels, mysteries, and misconceptions of vascular compensation to peripheral artery occlusion.

PubMed

Ziegler, Matthew A; Distasi, Matthew R; Bills, Randall G; Miller, Steven J; Alloosh, Mouhamad; Murphy, Michael P; Akingba, A George; Sturek, Michael; Dalsing, Michael C; Unthank, Joseph L

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation.

Marvels, Mysteries, and Misconceptions of Vascular Compensation to Peripheral Artery Occlusion

PubMed Central

ZIEGLER, MATTHEW A.; DISTASI, MATTHEW R.; BILLS, RANDALL G.; MILLER, STEVEN J.; ALLOOSH, MOUHAMAD; MURPHY, MICHAEL P.; AKINGBA, A. GEORGE; STUREK, MICHAEL; DALSING, MICHAEL C.; UNTHANK, JOSEPH L.

2010-01-01

Peripheral arterial disease is a major health problem and there is a significant need to develop therapies to prevent its progression to claudication and critical limb ischemia. Promising results in rodent models of arterial occlusion have generally failed to predict clinical success and led to questions of their relevance. While sub-optimal models may have contributed to the lack of progress, we suggest that advancement has also been hindered by misconceptions of the human capacity for compensation and the specific vessels which are of primary importance. We present and summarize new and existing data from humans, Ossabaw miniature pigs, and rodents which provide compelling evidence that natural compensation to occlusion of a major artery (i) may completely restore perfusion, (ii) occurs in specific pre-existing small arteries, rather than the distal vasculature, via mechanisms involving flow-mediated dilation and remodeling (iii) is impaired by cardiovascular risk factors which suppress the flow-mediated mechanisms and (iv) can be restored by reversal of endothelial dysfunction. We propose that restoration of the capacity for flow-mediated dilation and remodeling in small arteries represents a largely unexplored potential therapeutic opportunity to enhance compensation for major arterial occlusion and prevent the progression to critical limb ischemia in the peripheral circulation. PMID:20141596

Case report of a 28-year-old male with the rapid progression of steroid-resistant central nervous system vasculitis diagnosed by a brain biopsy.

PubMed

Takahashi, Keigo; Sato, Hideki; Hattori, Hidenori; Takao, Masaki; Takahashi, Shinichi; Suzuki, Norihiro

2017-09-30

A 28-year-old Japanese male without a significant past medical history presented with new-onset generalized clonic seizure and headache. A brain MRI revealed multiple enhanced lesions on both cerebral hemispheres. Laboratory exams showed no evidence of systemic inflammation or auto-immune antibodies such as ANCAs. Despite four courses of high-dose methylprednisolone pulse therapy and five treatments with plasmapheresis, his symptoms worsened and the MRI lesions progressed rapidly. During these treatments, we performed a targeted brain biopsy, that revealed histological findings consistent with a predominant angiitis of parenchymal and subdural small vessels. He was provided with diagnosis of central nervous system vasculitis (CNSV). Subsequent cyclophosphamide pulse therapy enabled a progressive successful improvement of his symptoms. While diagnostic methods for CNSV remain controversial, histological findings are thought to be more useful in obtaining a more definitive diagnosis than findings in image studies, such as MRI and angiography. We suggest that a brain biopsy should be considered during the early period of cases with suspected CNSV and rapid clinical deterioration. We also detected human herpesvirus 7 (HHV-7) using PCR technology in brain biopsy specimens, however the relationship between CNSV and HHV-7 infection is unknow.

Pregnancy associated plasma protein-A links pregnancy and melanoma progression by promoting cellular migration and invasion

PubMed Central

Prithviraj, Prashanth; Anaka, Matthew; McKeown, Sonja J; Permezel, Michael; Walkiewicz, Marzena

2015-01-01

Melanoma is the most common cancer diagnosed in pregnant women and an aggressive course with poorer outcomes is commonly described during pregnancy or shortly after childbirth. The underlying mechanisms for this are not understood. Here, we report that melanoma migration, invasiveness and progression are promoted by pregnancy-associated plasma protein-A (PAPPA), a pregnancy-associated metalloproteinase produced by the placenta that increases the bioavailability of IGF1 by cleaving it from a circulating complex formed with IGFBP4. We show that PAPPA is widely expressed by metastatic melanoma tumors and is elevated in melanoma cells exhibiting mesenchymal, invasive and label-retaining phenotypes. Notably, inhibition of PAPPA significantly reduced invasion and migration of melanoma cells in vitro and in vivo within the embryonic chicken neural tube. PAPPA-enriched pregnancy serum treatment enhanced melanoma motility in vitro. Furthermore, we report that IGF1 can induce the phenotypic and functional effects of epithelial-to-mesenchymal transition (EMT) in melanoma cells. In this study, we establish a clear relationship between a pregnancy-associated protein PAPPA, melanoma and functional effects mediated through IGF1 that provides a plausible mechanism for accelerated melanoma progression during pregnancy. This opens the possibility of targeting the PAPPA/IGF1 axis therapeutically. PMID:25940796

Pregnancy associated plasma protein-A links pregnancy and melanoma progression by promoting cellular migration and invasion.

PubMed

Prithviraj, Prashanth; Anaka, Matthew; McKeown, Sonja J; Permezel, Michael; Walkiewicz, Marzena; Cebon, Jonathan; Behren, Andreas; Jayachandran, Aparna

2015-06-30

Melanoma is the most common cancer diagnosed in pregnant women and an aggressive course with poorer outcomes is commonly described during pregnancy or shortly after childbirth. The underlying mechanisms for this are not understood. Here, we report that melanoma migration, invasiveness and progression are promoted by Pregnancy-Associated Plasma Protein-A (PAPPA), a pregnancy-associated metalloproteinase produced by the placenta that increases the bioavailability of IGF1 by cleaving it from a circulating complex formed with IGFBP4. We show that PAPPA is widely expressed by metastatic melanoma tumors and is elevated in melanoma cells exhibiting mesenchymal, invasive and label-retaining phenotypes. Notably, inhibition of PAPPA significantly reduced invasion and migration of melanoma cells in vitro and in vivo within the embryonic chicken neural tube. PAPPA-enriched pregnancy serum treatment enhanced melanoma motility in vitro. Furthermore, we report that IGF1 can induce the phenotypic and functional effects of epithelial-to-mesenchymal transition (EMT) in melanoma cells. In this study, we establish a clear relationship between a pregnancy-associated protein PAPPA, melanoma and functional effects mediated through IGF1 that provides a plausible mechanism for accelerated melanoma progression during pregnancy. This opens the possibility of targeting the PAPPA/IGF1 axis therapeutically.

Recent Progress in Organic Electrodes for Li and Na Rechargeable Batteries.

PubMed

Lee, Sechan; Kwon, Giyun; Ku, Kyojin; Yoon, Kyungho; Jung, Sung-Kyun; Lim, Hee-Dae; Kang, Kisuk

2018-03-27

Organic rechargeable batteries, which use organics as electrodes, are excellent candidates for next-generation energy storage systems because they offer design flexibility due to the rich chemistry of organics while being eco-friendly and potentially cost efficient. However, their widespread usage is limited by intrinsic problems such as poor electronic conductivity, easy dissolution into liquid electrolytes, and low volumetric energy density. New types of organic electrode materials with various redox centers or molecular structures have been developed over the past few decades. Moreover, research aimed at enhancing electrochemical properties via chemical tuning has been at the forefront of organic rechargeable batteries research in recent years, leading to significant progress in their performance. Here, an overview of the current developments of organic rechargeable batteries is presented, with a brief history of research in this field. Various strategies for improving organic electrode materials are discussed with respect to tuning intrinsic properties of organics using molecular modification and optimizing their properties at the electrode level. A comprehensive understanding of the progress in organic electrode materials is provided along with the fundamental science governing their performance in rechargeable batteries thus a guide is presented to the optimal design strategies to improve the electrochemical performance for next-generation battery systems. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Behavioral Interventions for Enhancing Life Participation in behavioral variant Frontotemporal Dementia and Primary Progressive Aphasia

PubMed Central

Kortte, Kathleen B.; Rogalski, Emily J.

2013-01-01

Primary progressive aphasia (PPA) and behavioral-variant frontotemporal dementia (bvFTD) are clinical syndromes under the umbrella term “frontotemporal dementia (FTD)” and are caused by a neurodegenerative disease with an onset most typically in the productive years of adulthood. The cognitive and behavioral impairments associated with FTD interfere with the successful engagement in typical life roles, such as parenting, working, and maintenance of interpersonal relationships. There are currently no treatments to stop or slow the degenerative process and there are only very limited medication options for the management of the cognitive-behavioral symptoms. However, alternative, non-pharmacological interventions may offer significant benefit to the quality of life of the diagnosed individual. The goal of this paper is to provide an overview of the approaches available through neurorehabilitation and community-based services that facilitate successful engagement in life activities and promote optimal quality of life for the individuals and families living with FTD. It is hoped that as medical providers become more familiar with behavioral interventions, referrals for services will increase thereby allowing individuals with FTD and their caregivers to learn ways to adapt, adjust, and participate in life to the fullest despite the impairments from this progressive disease. PMID:23611353

Value of the portal venous phase in evaluation of treated hepatocellular carcinoma following transcatheter arterial chemoembolisation.

PubMed

Lam, A; Fernando, D; Sirlin, C C; Nayyar, M; Goodwin, S C; Imagawa, D K; Lall, C

2017-11-01

To evaluate the utility of the portal venous phase on multiphasic computed tomography (CT) after treatment of hepatocellular carcinoma (HCC) with trans-arterial chemoembolisation (TACE). This was a retrospective review of patients who underwent TACE for HCC between 1 April 2012 and 21 December 2014, with appropriate multiphasic, pre- and post-procedural CT examinations. The maximum non-contrast, arterial phase, and portal venous phase attenuation values of the tumour and tumour bed were evaluated within a region of interest (ROI), with values adjusted against background hepatic parenchyma. Linear regression analyses were performed for both the arterial and venous phases, to assess the level of enhancement and to determine if the venous phase had additional value in this setting. A total of 86 cases from 51 patients were reviewed. All pre-procedural CT examinations of lesions demonstrated arterial phase enhancement with portal venous and delayed phase washout compatible with HCC. The post-procedural CT examinations following TACE revealed expected decreased arterial enhancement. Sixty-five cases (76%) showed persistent non-enhancement on the portal venous phase following embolisation therapy. A total of 21 cases (24%), however, demonstrated progressive portal venous hyper enhancement. Linear regression analysis demonstrated a statistical significance between the difference in maximal arterial and portal venous enhancement in these cases. Following TACE, the treated lesion may demonstrate portal venous phase hyper-enhancement within the tumour bed. As such, full attention should be given to these images for comprehensive evaluation of tumour response following treatment. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

EZH2 promotes tumor progression via regulating VEGF-A/AKT signaling in non-small cell lung cancer.

PubMed

Geng, Jian; Li, Xiao; Zhou, Zhanmei; Wu, Chin-Lee; Dai, Meng; Bai, Xiaoyan

2015-04-10

Enhancer of Zeste Homologue 2 (EZH2) accounts for aggressiveness and unfavorable prognosis of tumor. We investigated the mechanisms and signaling pathways of EZH2 in non-small cell lung carcinoma (NSCLC) progression. Increased expression of EZH2, vascular endothelial growth factor-A (VEGF-A) and AKT phosphorylation correlated with differentiation, lymph node metastasis, size and TNM stage in NSCLC. There was a positive correlation between EZH2 and VEGF-A expression and high EZH2 expression, as an independent prognostic factor, predicted a shorter overall survival time for NSCLC patients. The expression of VEGF-A and phosphorylated Ser(473)-AKT, cell proliferation, migration and metastasis were enhanced in EZH2-overexpressing A549 cells, but inhibited in parental H2087 cells with EZH2 silencing or GSK126 treatment. AKT activity was enhanced by recombinant human VEGF-165 but suppressed by bevacizumab. An AKT inhibitor MK-2206 blocked VEGF-A expression and AKT phosphorylation in parental H2087 and EZH2-overexpressing A549 cells. EZH2 activity was not affected by either VEGF-A stimulation/depletion or MK-2206 inhibition. These results demonstrate that EZH2 promotes lung cancer progression via the VEGF-A/AKT signaling pathway. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Enhanced lithium ion battery cycling of silicon nanowire anodes by template growth to eliminate silicon underlayer islands.

PubMed

Cho, Jeong-Hyun; Picraux, S Tom

2013-01-01

It is well-known that one-dimensional nanostructures reduce pulverization of silicon (Si)-based anode materials during Li ion cycling because they allow lateral relaxation. However, even with improved designs, Si nanowire-based structures still exhibit limited cycling stability for extended numbers of cycles, with the specific capacity retention with cycling not showing significant improvements over commercial carbon-based anode materials. We have found that one important reason for the lack of long cycling stability can be the presence of milli- and microscale Si islands which typically form under nanowire arrays during their growth. Stress buildup in these Si island underlayers with cycling results in cracking, and the loss of specific capacity for Si nanowire anodes, due to progressive loss of contact with current collectors. We show that the formation of these parasitic Si islands for Si nanowires grown directly on metal current collectors can be avoided by growth through anodized aluminum oxide templates containing a high density of sub-100 nm nanopores. Using this template approach we demonstrate significantly enhanced cycling stability for Si nanowire-based lithium-ion battery anodes, with retentions of more than ~1000 mA·h/g discharge capacity over 1100 cycles.

Enhanced suppression of tumor growth by concomitant treatment of human lung cancer cells with suberoylanilide hydroxamic acid and arsenic trioxide

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chien, Chia-Wen; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 11490, Taiwan; Yao, Ju-Hsien

2011-11-15

The efficacy of arsenic trioxide (ATO) against acute promyelocytic leukemia (APL) and relapsed APL has been well documented. ATO may cause DNA damage by generating reactive oxygen intermediates. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, modulates gene and protein expression via histone-dependent or -independent pathways that may result in chromatin decondensation, cell cycle arrest, differentiation, and apoptosis. We investigated whether ATO and SAHA act synergistically to enhance the death of cancer cells. Our current findings showed that combined treatment with ATO and SAHA resulted in enhanced suppression of non-small-cell lung carcinoma in vitro in H1299 cells and in vivomore » in a xenograft mouse model. Flow cytometric analysis of annexin V+ cells showed that apoptotic cell death was significantly enhanced after combined treatment with ATO and SAHA. At the doses used, ATO did not interfere with cell cycle progression, but SAHA induced p21 expression and led to G1 arrest. A Comet assay demonstrated that ATO, but not SAHA, induced DNA strand breaks in H1299 cells; however, co-treatment with SAHA significantly increased ATO-induced DNA damage. Moreover, SAHA enhanced acetylation of histone H3 and sensitized genomic DNA to DNase I digestion. Our results suggest that SAHA may cause chromatin relaxation and increase cellular susceptibility to ATO-induced DNA damage. Combined administration of SAHA and ATO may be an effective approach to the treatment of lung cancer. -- Highlights: Black-Right-Pointing-Pointer ATO and SAHA are therapeutic agents with different action modes. Black-Right-Pointing-Pointer Combination of ATO and SAHA synergistically inhibits tumor cell growth. Black-Right-Pointing-Pointer SAHA loosens chromatin structure resulting in increased sensitivity to DNase I. Black-Right-Pointing-Pointer ATO-induced DNA damage and apoptosis are enhanced by co-treatment with SAHA.« less

Salmon cartilage proteoglycan suppresses mouse experimental colitis through induction of Foxp3{sup +} regulatory T cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitsui, Toshihito; Department of Digestive Surgery, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori 036-8562; Sashinami, Hiroshi

Research highlights: {yields} Salmon proteoglycan suppresses IL-10{sup -/-} cell transfer-induced colitis progression. {yields} Salmon proteoglycan suppresses Th1- and Th17-related factors in colitis mice. {yields} Salmon proteoglycan enhances Foxp3 expression. -- Abstract: Proteoglycans (PGs) are complex glycohydrates which are widely distributed in extracellular matrix (ECM). PGs are involved in the construction of ECM, cell proliferation and differentiation. ECM components are involved in transduction of proinflammatory responses, but it is still unknown whether PGs are involved in inflammatory response. In this study, we investigated the effect of PG extracted from salmon cartilage on the progression of experimental colitis-induced in severe combined immunodeficiencymore » mice by cell transfer from interleukin-10 (IL-10){sup -/-} mice. IL-10{sup -/-} cell-transferred mice showed weight loss, colon shortening and histological appearance of mild colitis. Daily oral administration of PG attenuated the clinical progression of colitis in a dose-dependent manner. Colitis-induced mice showed the elevated expression of IFN-{gamma}, IL-12, TNF-{alpha}, IL-21, IL-23p19, IL-6, IL-17A and retinoic acid-related orphan receptor {gamma}t (ROR{gamma}t) in lamina propria mononuclear cells (LPMCs) and oral administration of PG suppressed the expression of these factors. Conversely, expression of Foxp3 that induces CD4{sup +}CD25{sup +} regulatory T cells in LPMCs was enhanced by PG administration. These findings suggested that salmon PG attenuated the progression of colitis due to suppression of inflammatory response by enhancement of regulatory T cell induction.« less

Evoked-potential changes following discrimination learning involving complex sounds

PubMed Central

Orduña, Itzel; Liu, Estella H.; Church, Barbara A.; Eddins, Ann C.; Mercado, Eduardo

2011-01-01

Objective Perceptual sensitivities are malleable via learning, even in adults. We trained adults to discriminate complex sounds (periodic, frequency-modulated sweep trains) using two different training procedures, and used psychoacoustic tests and evoked potential measures (the N1-P2 complex) to assess changes in both perceptual and neural sensitivities. Methods Training took place either on a single day, or daily across eight days, and involved discrimination of pairs of stimuli using a single-interval, forced-choice task. In some participants, training started with dissimilar pairs that became progressively more similar across sessions, whereas in others training was constant, involving only one, highly similar, stimulus pair. Results Participants were better able to discriminate the complex sounds after training, particularly after progressive training, and the evoked potentials elicited by some of the sounds increased in amplitude following training. Significant amplitude changes were restricted to the P2 peak. Conclusion Our findings indicate that changes in perceptual sensitivities parallel enhanced neural processing. Significance These results are consistent with the proposal that changes in perceptual abilities arise from the brain’s capacity to adaptively modify cortical representations of sensory stimuli, and that different training regimens can lead to differences in cortical sensitivities, even after relatively short periods of training. PMID:21958655

Activation of the CXCL16/CXCR6 Axis by TNF-α Contributes to Ectopic Endometrial Stromal Cells Migration and Invasion.

PubMed

Peng, Yaoming; Ma, Junyan; Lin, Jun

2018-01-01

The activation of systemic and local inflammatory mechanisms, including elevated levels of chemokines and proinflammatory cytokines in endometriosis progression, is becoming more evident in the recent years. Here, we report the involvement of CXC chemokine 16 (CXCL16) and its sole receptor, CXC chemokine receptor 6 (CXCR6), in pathophysiology of endometriosis. Expression of CXCL16, but not CXCR6, was significantly upregulated in endometriotic lesions when compared to control endometrium. Additionally, serum CXCL16 was significantly elevated in women with endometriosis when compared to control group. Moreover, blockade of the CXCL16/CXCR6 axis by CXCR6 small-interfering RNA reduced the migration and invasion of ectopic endometrial stromal cells (EESCs) followed by decreased phosphorylation of ERK1/2. Furthermore, TNF-α treatment induced the expression of CXCL16 in EESCs. In conclusion, these results suggest that CXCL16/CXCR6 axis, whose expression was enhanced by TNF-α, may be associated with the increased motility of EESCs, through regulation of ERK1/2 signaling, thus contributing to the development of endometriosis. These findings indicate that the CXCL16/CXCR6 axis may contribute to the progression of endometriosis and could be served as a potential target for diagnosis and treatment.

The role of stress sensitization in progression of posttraumatic distress following deployment.

PubMed

Smid, Geert E; Kleber, Rolf J; Rademaker, Arthur R; van Zuiden, Mirjam; Vermetten, Eric

2013-11-01

Military personnel exposed to combat are at risk for experiencing post-traumatic distress that can progress over time following deployment. We hypothesized that progression of post-traumatic distress may be related to enhanced susceptibility to post-deployment stressors. This study aimed at examining the concept of stress sensitization prospectively in a sample of Dutch military personnel deployed in support of the conflicts in Afghanistan. In a cohort of soldiers (N = 814), symptoms of post-traumatic stress disorder (PTSD) were assessed before deployment as well as 2, 7, 14, and 26 months (N = 433; 53 %) after their return. Data were analyzed using latent growth modeling. Using multiple group analysis, we examined whether high combat stress exposure during deployment moderated the relation between post-deployment stressors and linear change in post-traumatic distress after deployment. A higher baseline level of post-traumatic distress was associated with more early life stressors (standardized regression coefficient = 0.30, p < 0.001). In addition, a stronger increase in posttraumatic distress during deployment was associated with more deployment stressors (standardized coefficient = 0.21, p < 0.001). A steeper linear increase in posttraumatic distress post-deployment (from 2 to 26 months) was predicted by more post-deployment stressors (standardized coefficient = 0.29, p < 0.001) in high combat stress exposed soldiers, but not in a less combat stress exposed group. The group difference in the predictive effect of post-deployment stressors on progression of post-traumatic distress was significant (χ²(1) = 7.85, p = 0.005). Progression of post-traumatic distress following combat exposure may be related to sensitization to the effects of post-deployment stressors during the first year following return from deployment.

Katabatic winds diminish precipitation contribution to the Antarctic ice mass balance.

PubMed

Grazioli, Jacopo; Madeleine, Jean-Baptiste; Gallée, Hubert; Forbes, Richard M; Genthon, Christophe; Krinner, Gerhard; Berne, Alexis

2017-10-10

Snowfall in Antarctica is a key term of the ice sheet mass budget that influences the sea level at global scale. Over the continental margins, persistent katabatic winds blow all year long and supply the lower troposphere with unsaturated air. We show that this dry air leads to significant low-level sublimation of snowfall. We found using unprecedented data collected over 1 year on the coast of Adélie Land and simulations from different atmospheric models that low-level sublimation accounts for a 17% reduction of total snowfall over the continent and up to 35% on the margins of East Antarctica, significantly affecting satellite-based estimations close to the ground. Our findings suggest that, as climate warming progresses, this process will be enhanced and will limit expected precipitation increases at the ground level.

Katabatic winds diminish precipitation contribution to the Antarctic ice mass balance

PubMed Central

Grazioli, Jacopo; Madeleine, Jean-Baptiste; Gallée, Hubert; Forbes, Richard M.; Genthon, Christophe; Krinner, Gerhard; Berne, Alexis

2017-01-01

Snowfall in Antarctica is a key term of the ice sheet mass budget that influences the sea level at global scale. Over the continental margins, persistent katabatic winds blow all year long and supply the lower troposphere with unsaturated air. We show that this dry air leads to significant low-level sublimation of snowfall. We found using unprecedented data collected over 1 year on the coast of Adélie Land and simulations from different atmospheric models that low-level sublimation accounts for a 17% reduction of total snowfall over the continent and up to 35% on the margins of East Antarctica, significantly affecting satellite-based estimations close to the ground. Our findings suggest that, as climate warming progresses, this process will be enhanced and will limit expected precipitation increases at the ground level. PMID:28973875

Hypercellularity Components of Glioblastoma Identified by High b-Value Diffusion-Weighted Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pramanik, Priyanka P.; Parmar, Hemant A.; Mammoser, Aaron G.

2015-07-15

Purpose: Use of conventional magnetic resonance imaging (MRI) for target definition may expose glioblastomas (GB) to inadequate radiation dose coverage of the nonenhanced hypercellular subvolume. This study aimed to develop a technique to identify the hypercellular components of GB by using high b-value diffusion-weighted imaging (DWI) and to investigate its relationship with the prescribed 95% isodose volume (PDV) and progression-free survival (PFS). Methods and Materials: Twenty-one patients with GB underwent chemoradiation therapy post-resection and biopsy. Radiation therapy (RT) treatment planning was based upon conventional MRI. Pre-RT DWIs were acquired in 3 orthogonal directions with b-values of 0, 1000, and 3000more » s/mm{sup 2}. Hypercellularity volume (HCV) was defined on the high b-value (3000 s/mm{sup 2}) DWI by a threshold method. Nonenhanced signified regions not covered by the Gd-enhanced gross tumor volume (GTV-Gd) on T1-weighted images. The PDV was used to evaluate spatial coverage of the HCV by the dose plan. Association between HCV and PFS or other clinical covariates were assessed using univariate proportional hazards regression models. Results: HCVs and nonenhanced HCVs varied from 0.58 to 67 cm{sup 3} (median: 9.8 cm{sup 3}) and 0.15 to 60 cm{sup 3} (median: 2.5 cm{sup 3}), respectively. Fourteen patients had incomplete dose coverage of the HCV, 6 of whom had >1 cm{sup 3} HCV missed by the 95% PDV (range: 1.01-25.4 cm{sup 3}). Of the 15 patients who progressed, 5 progressed earlier, within 6 months post-RT, and 10 patients afterward. Pre-RT HCVs within recurrent GTVs-Gd were 78% (range: 65%-89%) for the 5 earliest progressions but lower, 53% (range: 0%-85%), for the later progressions. HCV and nonenhanced HCV were significant negative prognostic indicators for PFS (P<.002 and P<.01, respectively). The hypercellularity subvolume not covered by the 95% PDV was a significant negative predictor for PFS (P<.05). Conclusions: High b-value DWI identifies the hypercellular components of GB and could aid in RT target volume definition. Future studies will allow us to investigate the role of high b-value DWI in identifying radiation boost volumes and diagnosing progression.« less

Coaching Doctoral Students--A Means to Enhance Progress and Support Self-Organisation in Doctoral Education

ERIC Educational Resources Information Center

Godskesen, Mirjam; Kobayashi, Sofie

2016-01-01

In this paper we focus on individual coaching carried out by an external coach as a new pedagogical element that can impact doctoral students' sense of progress in doctoral education. The study used a mixed-methods approach in that we draw on quantitative and qualitative data from the evaluation of a project on coaching doctoral students. We…

Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer.

PubMed

Lin, Mao; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, Lizhi; Xu, Kecheng

2017-10-10

In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 -15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, P = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, P = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, P < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, P < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer.

Cryoablation combined with allogenic natural killer cell immunotherapy improves the curative effect in patients with advanced hepatocellular cancer

PubMed Central

Lin, Mao; Liang, Shuzhen; Wang, Xiaohua; Liang, Yinqing; Zhang, Mingjie; Chen, Jibing; Niu, Lizhi; Xu, Kecheng

2017-01-01

In this study, the clinical efficacy of cryosurgery combined with allogenic natural killer cell immunotherapy for advanced hepatocellular cancer was evaluated. From October 2015 to March 2017, we enrolled 61 patients who met the enrollment criteria and divided them into two groups: 1) the simple cryoablation group (Cryo group, n = 26); and 2) the cryoablation combined with allogenic natural killer cells group (Cryo-NK group, n = 35), the safety and short-term effects were evaluated firstly, then the median progression-free survival, response rate and disease control rate were assessed. All adverse events experienced by the patients were recorded, and included local (e.g., pain, pleural effusion, and ascites) and systemic (e.g., chills, fatigue, and fever) reactions, fever was more frequent. Other possible seriously side effects (e.g., blood or bone marrow changes) were not detected. Combining allogeneic natural killer cells with cryoablation had a synergistic effect, not only enhancing the immune function, improving the quality of life of the patients, but also reducing the expression of AFP and significantly exhibiting good clinical efficacy of the patients. After a median follow-up of 8.7 months (3.9 –15.1months), median progression-free survival was higher in Cryo-NK (9.1 months) than in Cryo (7.6 months, P = 0.0107), median progression-free survival who received multiple natural killer was higher than who just received single natural killer (9.7 months vs.8.4 months, P = 0.0011, respectively), the response rate in Cryo-NK (60.0%) was higher than in Cryo (46.1%, P < 0.05), the disease control rate in Cryo-NK (85.7%) was higher than in Cryo group (69.2%, P < 0.01). Percutaneous cryoablation combined with allogeneic natural killer cell immunotherapy significantly increased median progression-free survival of advanced hepatocellular cancer patients. Multiple allogeneic natural killer cells infusion was associated with better prognosis to advanced hepatocellular cancer. PMID:29137237

Motor, cognitive, and functional declines contribute to a single progressive factor in early HD.

PubMed

Schobel, Scott A; Palermo, Giuseppe; Auinger, Peggy; Long, Jeffrey D; Ma, Shiyang; Khwaja, Omar S; Trundell, Dylan; Cudkowicz, Merit; Hersch, Steven; Sampaio, Cristina; Dorsey, E Ray; Leavitt, Blair R; Kieburtz, Karl D; Sevigny, Jeffrey J; Langbehn, Douglas R; Tabrizi, Sarah J

2017-12-12

To identify an improved measure of clinical progression in early Huntington disease (HD) using data from prospective observational cohort studies and placebo group data from randomized double-blind clinical trials. We studied Unified Huntington Disease Rating Scale (UHDRS) and non-UHDRS clinical measures and brain measures of progressive atrophy in 1,668 individuals with early HD followed up prospectively for up to 30 to 36 months of longitudinal clinical follow-up. The results demonstrated that a composite measure of motor, cognitive, and global functional decline best characterized clinical progression and was most strongly associated with brain measures of progressive corticostriatal atrophy. Use of a composite motor, cognitive, and global functional clinical outcome measure in HD provides an improved measure of clinical progression more related to measures of progressive brain atrophy and provides an opportunity for enhanced clinical trial efficiency relative to currently used individual motor, cognitive, and functional outcome measures. © 2017 American Academy of Neurology.

Identifying Areas of Tension in the Field of Technology-Enhanced Learning: Results of an International Delphi Study

ERIC Educational Resources Information Center

Plesch, Christine; Kaendler, Celia; Rummel, Nikol; Wiedmann, Michael; Spada, Hans

2013-01-01

Despite steady progress in research in technology-enhanced learning (TEL), the translation of research findings and technology into educational practices falls short of expectations. We present five Areas of Tension which were identified and evaluated in an international Delphi study on TEL. These tensions might impede a more comprehensive…