These are representative sample records from Science.gov related to your search topic.
For comprehensive and current results, perform a real-time search at Science.gov.
1

Multiple Differential Aperture Microscopy  

SciTech Connect

Differential-aperture X-ray microscopy (DAXM) is a powerful approach to 3D tomography with particular relevance to X-ray microdiffraction. With DAXM, scattering from submicron volumes can be resolved. However, the method is intrinsically a scanning technique where every resolved volume element (voxel) requires at least one area-detector readout. Previous applications of DAXM have used a single wire for knife-edge step profiling. Here, we demonstrate a way to accelerate DAXM measurements using multiple wires. A proof-of-principle experiment with a three-wire prototype showed that the speed of measurements can be tripled, but careful calibrations of wires will be required to maintain the spatial accuracy. In addition, related possibilities for accelerating measurements are briefly discussed.

Chung, Jin-Seok [ORNL; Isa, Saliman Anavami [ORNL; Greene, Virgil [ORNL; Broadwater, Ombreyan Q [ORNL; Liu, W. [Argonne National Laboratory (ANL); Ice, Gene E [ORNL

2007-01-01

2

Label-Free Morphology-Based Prediction of Multiple Differentiation Potentials of Human Mesenchymal Stem Cells for Early Evaluation of Intact Cells  

PubMed Central

Precise quantification of cellular potential of stem cells, such as human bone marrow–derived mesenchymal stem cells (hBMSCs), is important for achieving stable and effective outcomes in clinical stem cell therapy. Here, we report a method for image-based prediction of the multiple differentiation potentials of hBMSCs. This method has four major advantages: (1) the cells used for potential prediction are fully intact, and therefore directly usable for clinical applications; (2) predictions of potentials are generated before differentiation cultures are initiated; (3) prediction of multiple potentials can be provided simultaneously for each sample; and (4) predictions of potentials yield quantitative values that correlate strongly with the experimental data. Our results show that the collapse of hBMSC differentiation potentials, triggered by in vitro expansion, can be quantitatively predicted far in advance by predicting multiple potentials, multi-lineage differentiation potentials (osteogenic, adipogenic, and chondrogenic) and population doubling potential using morphological features apparent during the first 4 days of expansion culture. In order to understand how such morphological features can be effective for advance predictions, we measured gene-expression profiles of the same early undifferentiated cells. Both senescence-related genes (p16 and p21) and cytoskeleton-related genes (PTK2, CD146, and CD49) already correlated to the decrease of potentials at this stage. To objectively compare the performance of morphology and gene expression for such early prediction, we tested a range of models using various combinations of features. Such comparison of predictive performances revealed that morphological features performed better overall than gene-expression profiles, balancing the predictive accuracy with the effort required for model construction. This benchmark list of various prediction models not only identifies the best morphological feature conversion method for objective potential prediction, but should also allow clinicians to choose the most practical morphology-based prediction method for their own purposes. PMID:24705458

Sasaki, Hiroto; Takeuchi, Ichiro; Okada, Mai; Sawada, Rumi; Kanie, Kei; Kiyota, Yasujiro; Honda, Hiroyuki; Kato, Ryuji

2014-01-01

3

Multiple Intelligences for Differentiated Learning  

ERIC Educational Resources Information Center

There is an intricate literacy to Gardner's multiple intelligences theory that unlocks key entry points for differentiated learning. Using a well-articulated framework, rich with graphic representations, Williams provides a comprehensive discussion of multiple intelligences. He moves the teacher and students from curiosity, to confidence, to…

Williams, R. Bruce

2007-01-01

4

Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response  

PubMed Central

The prevalence of multiple sclerosis (MS) in the Gulf region has markedly increased during the last decade, but the mechanisms of the disease have not been investigated. The present study aimed to understand the molecular processes involved in the disease development of the recently emerged MS in this population using microarray technology to investigate differentially-expressed novel genes in MS patients compared to healthy-matched subjects. The expression of the upregulated genes was confirmed by quantitative polymerase chain reaction (qPCR). Furthermore, gene cloning, protein expression and purification were performed followed by testing of the obtained recombinant protein on biological assays, including cell proliferation and cytokine mRNA detection by reverse transcriptase-qPCR. The results showed that out of ~50,000 genes, the hypothetical transmembrane protein-66 gene (TMEM66) exhibited a 3 times higher expression in MS patients compared to healthy subjects. The TMEM66 gene was cloned and its protein showed marked immunological activity relevant to MS since significant proliferation (P<0.05) and augmented induction of the proinflammatory cytokines, interleukin (IL)-6, interferon-?, tumor necrosis factor-?, and the chemokines, chemokine ligand 5/chemokine receptor 5, macrophage inflammatory protein 1? (MIP-1?) and MIP-1? were recorded, but not the anti-inflammatory cytokines, IL-4 or IL-2. In conclusion, TMEM66 may be associated with the molecular events of MS and may be considered as an MS biomarker for future personalized medicine management approaches. PMID:25469256

TAHA, SAFA; ALJISHI, MUNA; ALSHAROQI, ISA; BAKHIET, MOIZ

2015-01-01

5

Differential upregulation of the hypothetical transmembrane protein 66 (TMEM66) in multiple sclerosis patients with potential inflammatory response.  

PubMed

The prevalence of multiple sclerosis (MS) in the Gulf region has markedly increased during the last decade, but the mechanisms of the disease have not been investigated. The present study aimed to understand the molecular processes involved in the disease development of the recently emerged MS in this population using microarray technology to investigate differentially-expressed novel genes in MS patients compared to healthy-matched subjects. The expression of the upregulated genes was confirmed by quantitative polymerase chain reaction (qPCR). Furthermore, gene cloning, protein expression and purification were performed followed by testing of the obtained recombinant protein on biological assays, including cell proliferation and cytokine mRNA detection by reverse transcriptase-qPCR. The results showed that out of ~50,000 genes, the hypothetical transmembrane protein-66 gene (TMEM66) exhibited a 3 times higher expression in MS patients compared to healthy subjects. The TMEM66 gene was cloned and its protein showed marked immunological activity relevant to MS since significant proliferation (P<0.05) and augmented induction of the proinflammatory cytokines, interleukin (IL)-6, interferon-?, tumor necrosis factor-?, and the chemokines, chemokine ligand 5/chemokine receptor 5, macrophage inflammatory protein 1? (MIP-1?) and MIP-1? were recorded, but not the anti-inflammatory cytokines, IL-4 or IL-2. In conclusion, TMEM66 may be associated with the molecular events of MS and may be considered as an MS biomarker for future personalized medicine management approaches. PMID:25469256

Taha, Safa; Aljishi, Muna; Alsharoqi, Isa; Bakhiet, Moiz

2015-01-01

6

Integration of Multiple Signaling Regulates through Apoptosis the Differential Osteogenic Potential of Neural Crest-Derived and Mesoderm-Derived Osteoblasts  

PubMed Central

Neural crest-derived (FOb) and mesoderm-derived (POb) calvarial osteoblasts are characterized by distinct differences in their osteogenic potential. We have previously demonstrated that enhanced activation of endogenous FGF and Wnt signaling confers greater osteogenic potential to FOb. Apoptosis, a key player in bone formation, is the main focus of this study. In the current work, we have investigated the apoptotic activity of FOb and POb cells during differentiation. We found that lower apoptosis, as measured by caspase-3 activity is a major feature of neural crest-derived osteoblast which also have higher osteogenic capacity. Further investigation indicated TGF-? signaling as main positive regulator of apoptosis in these two populations of calvarial osteoblasts, while BMP and canonical Wnt signaling negatively regulate the process. By either inducing or inhibiting these signaling pathways we could modulate apoptotic events and improve the osteogenic potential of POb. Taken together, our findings demonstrate that integration of multiple signaling pathways contribute to imparting greater osteogenic potential to FOb by decreasing apoptosis. PMID:23536803

Li, Shuli; Meyer, Nathaniel P.; Quarto, Natalina; Longaker, Michael T.

2013-01-01

7

Multiple differential-aperture microscopy.  

SciTech Connect

Differential-aperture X-ray microscopy (DAXM) is a powerful approach to 3D tomography with particular relevance to X-ray microdiffraction. With DAXM, scattering from submicron volumes can be resolved. However, the method is intrinsically a scanning technique where every resolved volume element (voxel) requires at least one area-detector readout. Previous applications of DAXM have used a single wire for knife-edge step profiling. Here, we demonstrate a way to accelerate DAXM measurements using multiple wires. A proof-of-principle experiment with a three-wire prototype showed that the speed of measurements can be tripled, but careful calibrations of wires will be required to maintain the spatial accuracy. In addition, related possibilities for accelerating measurements are briefly discussed.

Chung, J.-S.; Isa, S.; Greene, V.; Broadwater, O.; Liu, W.; Ice, G. E.; ORNL; Soongsil Univ.; South Carolina State Univ.

2007-01-01

8

Hertz Potentials and Differential Geometry  

E-print Network

. . . . . . . . . . . . . . . . . . . . . . . 34 C. Non-Trivial Topology . . . . . . . . . . . . . . . . . . . . . 35 V HERTZ POTENTIALS AND DIFFERENTIAL GEOMETRY : 36 A. Hertz Potential 2-Forms . . . . . . . . . . . . . . . . . . . 36 B. Gauge Invariance... . . . . . . . . . . . . . . . . . . . . . . . 37 C. Scalar Hertz Potentials . . . . . . . . . . . . . . . . . . . . 39 D. Higher-Order Gauge Transformations . . . . . . . . . . . . 47 E. Non-Trivial Topology . . . . . . . . . . . . . . . . . . . . . 49 v CHAPTER Page VI APPLICATIONS...

Bouas, Jeffrey David

2011-08-08

9

Multiple-symbol differential detection of MPSK  

NASA Technical Reports Server (NTRS)

A differential detection technique for MPSK (multiple-phase shift keying), which uses a multiple-symbol observation interval, is presented, and its performance is analyzed and simulated. The technique makes use of maximum-likelihood sequence estimation of the transmitted phases rather than symbol-by-symbol detection as in conventional differential detection. Thus, the performance of this multiple-symbol detection scheme fills the gap between conventional (two-symbol observation) differentially coherent detection of MPSK and ideal coherent of MPSK with differential encoding. The amount of improvement gained over conventional differential detection depends on the number of phases M and the number of additional symbol intervals added to the observation. What is particularly interesting is that substantial performance improvement can be obtained for only one or two additional symbol intervals of observation. The analysis and simulation results presented are for uncoded MPSK.

Divsalar, Dariush; Simon, Marvin K.

1990-01-01

10

Multiple-Bit Differential Detection of OQPSK  

NASA Technical Reports Server (NTRS)

A multiple-bit differential-detection method has been proposed for the reception of radio signals modulated with offset quadrature phase-shift keying (offset QPSK or OQPSK). The method is also applicable to other spectrally efficient offset quadrature modulations. This method is based partly on the same principles as those of a multiple-symbol differential-detection method for M-ary QPSK, which includes QPSK (that is, non-offset QPSK) as a special case. That method was introduced more than a decade ago by the author of the present method as a means of improving performance relative to a traditional (two-symbol observation) differential-detection scheme. Instead of symbol-by-symbol detection, both that method and the present one are based on a concept of maximum-likelihood sequence estimation (MLSE). As applied to the modulations in question, MLSE involves consideration of (1) all possible binary data sequences that could have been received during an observation time of some number, N, of symbol periods and (2) selection of the sequence that yields the best match to the noise-corrupted signal received during that time. The performance of the prior method was shown to range from that of traditional differential detection for short observation times (small N) to that of ideal coherent detection (with differential encoding) for long observation times (large N).

Simon, Marvin

2005-01-01

11

Estimating differential expression from multiple indicators  

PubMed Central

Regardless of the advent of high-throughput sequencing, microarrays remain central in current biomedical research. Conventional microarray analysis pipelines apply data reduction before the estimation of differential expression, which is likely to render the estimates susceptible to noise from signal summarization and reduce statistical power. We present a probe-level framework, which capitalizes on the high number of concurrent measurements to provide more robust differential expression estimates. The framework naturally extends to various experimental designs and target categories (e.g. transcripts, genes, genomic regions) as well as small sample sizes. Benchmarking in relation to popular microarray and RNA-sequencing data-analysis pipelines indicated high and stable performance on the Microarray Quality Control dataset and in a cell-culture model of hypoxia. Experimental-data-exhibiting long-range epigenetic silencing of gene expression was used to demonstrate the efficacy of detecting differential expression of genomic regions, a level of analysis not embraced by conventional workflows. Finally, we designed and conducted an experiment to identify hypothermia-responsive genes in terms of monotonic time-response. As a novel insight, hypothermia-dependent up-regulation of multiple genes of two major antioxidant pathways was identified and verified by quantitative real-time PCR. PMID:24586062

Ilmjärv, Sten; Hundahl, Christian Ansgar; Reimets, Riin; Niitsoo, Margus; Kolde, Raivo; Vilo, Jaak; Vasar, Eero; Luuk, Hendrik

2014-01-01

12

Differential diagnosis of suspected multiple sclerosis: a consensus approach  

PubMed Central

Background and objectives Diagnosis of multiple sclerosis (MS) requires exclusion of diseases that could better explain the clinical and paraclinical findings. A systematic process for exclusion of alternative diagnoses has not been defined. An International Panel of MS experts developed consensus perspectives on MS differential diagnosis. Methods Using available literature and consensus, we developed guidelines for MS differential diagnosis, focusing on exclusion of potential MS mimics, diagnosis of common initial isolated clinical syndromes, and differentiating between MS and non-MS idiopathic inflammatory demyelinating diseases. Results We present recommendations for 1) clinical and paraclinical red flags suggesting alternative diagnoses to MS; 2) more precise definition of “clinically isolated syndromes” (CIS), often the first presentations of MS or its alternatives; 3) algorithms for diagnosis of three common CISs related to MS in the optic nerves, brainstem, and spinal cord; and 4) a classification scheme and diagnosis criteria for idiopathic inflammatory demyelinating disorders of the central nervous system. Conclusions Differential diagnosis leading to MS or alternatives is complex and a strong evidence base is lacking. Consensus-determined guidelines provide a practical path for diagnosis and will be useful for the non-MS specialist neurologist. Recommendations are made for future research to validate and support these guidelines. Guidance on the differential diagnosis process when MS is under consideration will enhance diagnostic accuracy and precision. PMID:18805839

Miller, DH; Weinshenker, BG; Filippi, M; Banwell, BL; Cohen, JA; Freedman, MS; Galetta, SL; Hutchinson, M; Johnson, RT; Kappos, L; Kira, J; Lublin, FD; McFarland, HF; Montalban, X; Panitch, H; Richert, JR; Reingold, SC; Polman, CH

2008-01-01

13

Lesion morphology at 7 Tesla MRI differentiates Susac syndrome from multiple sclerosis  

Microsoft Academic Search

BACKGROUND: Although an orphan disease with still obscure aetiopathogenesis, Susac syndrome has to be considered as differential diagnosis in multiple sclerosis (MS), since its clinical presentation and paraclinical features including routine magnetic resonance imaging (MRI) findings partially overlap. OBJECTIVE: We aimed to study a potential benefit of 7T MRI for (i) the differentiation between Susac syndrome and MS and (ii)

J. Wuerfel; T. Sinnecker; E. B. Ringelstein; W. Schwindt; T. Niendorf; F. Paul; I. Kleffner; J. Dorr

2012-01-01

14

Multiple criteria differential expression analysis of microarray data  

E-print Network

from biological data. ! Data Mining: Algorithms for extracting information from huge datasets using aberrations, gain settings ! Imaging and Extraction ­ misaligned spot grid, segmentation Microarray dataMultiple criteria differential expression analysis of microarray data Alfred O. Hero III University

Hero, Alfred O.

15

Effect of Multiple Testing Adjustment in Differential Item Functioning Detection  

ERIC Educational Resources Information Center

In a typical differential item functioning (DIF) analysis, a significance test is conducted for each item. As a test consists of multiple items, such multiple testing may increase the possibility of making a Type I error at least once. The goal of this study was to investigate how to control a Type I error rate and power using adjustment…

Kim, Jihye; Oshima, T. C.

2013-01-01

16

Multiple symbol differential detection of uncoded and trellis coded MPSK  

NASA Technical Reports Server (NTRS)

A differential detection for MPSK, which uses a multiple symbol observation interval, is presented and its performance analyzed and simulated. The technique makes use of maximum-likelihood sequence estimation of the transmitted phases rather than symbol-by-symbol detection as in conventional differential detection. As such the performance of this multiple symbol detection scheme fills the gap between conventional (two-symbol observation) differentially coherent detection of MPSK and ideal coherent of MPSK with differential encoding. The amount of improvement gained over conventional differential detection depends on the number of phases, M, and the number of additional symbol intervals added to the observation. What is particularly interesting is that substantial performance improvement can be obtained for only one or two additional symbol intervals of observation. The analysis and simulation results presented are for uncoded and trellis coded MPSK.

Divsalar, Dariush; Simon, Marvin K.; Shahshahani, Mehrdad

1989-01-01

17

[Differential aspects of multiple sclerosis and chronic borrelial encephalomyelitis].  

PubMed

The Yaroslavl region is an endemic area for Lyme disease (LD) with one of the highest levels of morbidity in Russia. Chronic neuroborreliosis can mimic multiple sclerosis and cause considerable difficulties in differential diagnosis. A comparative clinical-instrumental analysis of patients with definite multiple sclerosis (n=65) and chronic borrelial encephalomyelitis (n=11) was carried out. The key differential-diagnostic features of multiple sclerosis and borrelial encephalomyelitis were specified. Migrating erythema and tick's bite in the anamnesis, combined with lesions of the central and peripheral nervous systems, the absence of retrobulbar neuritis in the anamnesis, artralgia and myalgia, the high blood sedimentation rate were not characteristic of multiple sclerosis. A patient with abovementioned findings should be tested for the presence of antibodies to Borrelia burgdorferi in the blood serum and, if necessary, in the cerebrospinal fluid to exclude the diagnosis of Lime disease. PMID:21947065

Spirin, N N; Baranova, N S; Fadeeva, O A; Shipova, E G; Stepanov, I O

2011-01-01

18

Adiabatic potentials using multiple radio frequencies  

E-print Network

Adiabatic radio frequency (RF) potentials are powerful tools for creating advanced trapping geometries for ultra-cold atoms. While the basic theory of RF trapping is well understood, studies of more complicated setups involving multiple resonant frequencies in the limit where their effects cannot be treated independently are rare. Here we present an approach based on Floquet theory and show that it offers significant corrections to existing models when two RF frequencies are near degenerate. Furthermore it has no restrictions on the dimension, the number of frequencies or the orientation of the RF fields. We show that the added degrees of freedom can, for example, be used to create a potential that allows for easy creation of ring vortex solitons.

T. Morgan; Th. Busch; T. Fernholz

2014-05-11

19

Differential Item Functioning Detection Using the Multiple Indicators, Multiple Causes Method with a Pure Short Anchor  

ERIC Educational Resources Information Center

The multiple indicators, multiple causes (MIMIC) method with a pure short anchor was proposed to detect differential item functioning (DIF). A simulation study showed that the MIMIC method with an anchor of 1, 2, 4, or 10 DIF-free items yielded a well-controlled Type I error rate even when such tests contained as many as 40% DIF items. In general,…

Shih, Ching-Lin; Wang, Wen-Chung

2009-01-01

20

Testing for Nonuniform Differential Item Functioning with Multiple Indicator Multiple Cause Models  

ERIC Educational Resources Information Center

In extant literature, multiple indicator multiple cause (MIMIC) models have been presented for identifying items that display uniform differential item functioning (DIF) only, not nonuniform DIF. This article addresses, for apparently the first time, the use of MIMIC models for testing both uniform and nonuniform DIF with categorical indicators. A…

Woods, Carol M.; Grimm, Kevin J.

2011-01-01

21

Multiple Symbol Differential Detection and Optimization of Differentially Modulated (N,M)APSK  

Microsoft Academic Search

A decision-feedback multiple symbol differential detection of differentially modulated 16-order (N,M)APSK signal, that is N-PSK on the inner ring and M-PSK on the outer ring (N+M=16), is presented, as well as the optimization of constellation according to the minimum SER (symbol-error-rate). Here we have studied the detection performance, and derived the theoretical expression of SER. It can been seen that

Xiao-Qing Fang; Pei-Xia Xu; Wen-Gang Mi

2006-01-01

22

Multiple scales analysis of a nonlinear ordinary differential equation  

Microsoft Academic Search

Asymptotic solutions of the nonlinear ordinary differential equation d2?\\/dZ2 +a d?\\/dZ +f(?)=0 for large a are obtained by the singular perturbation method of multiple scales analysis. They are in the form of ?(Z)=A(Z\\/a)+B(Z\\/a)exp(?aZ). Initial and boundary value problems are discussed. The special case of f(?)=?+cos 2?(?<1), encountered in shearing nematic liquid crystal soliton problems and other physical systems, is solved

Gang Xu; Changqing Shu; Lei Lin

1985-01-01

23

A multiple exp-function method for nonlinear differential equations and its application  

E-print Network

A multiple exp-function method to exact multiple wave solutions of nonlinear partial differential equations is proposed. The method is oriented towards ease of use and capability of computer algebra systems, and provides a direct and systematical solution procedure which generalizes Hirota's perturbation scheme. With help of Maple, an application of the approach to the $3+1$ dimensional potential-Yu-Toda-Sasa-Fukuyama equation yields exact explicit 1-wave and 2-wave and 3-wave solutions, which include 1-soliton, 2-soliton and 3-soliton type solutions. Two cases with specific values of the involved parameters are plotted for each of 2-wave and 3-wave solutions.

Wen-Xiu Ma; Tingwen Huang; Yi Zhang

2010-10-16

24

Potential of Urinary Metabolites for Diagnosing Multiple Sclerosis Teklab Gebregiworgis,,  

E-print Network

Potential of Urinary Metabolites for Diagnosing Multiple Sclerosis Teklab Gebregiworgis ABSTRACT: A definitive diagnostic test for multiple sclerosis (MS) does not exist; instead physicians use healthy and MS drug-treated EAE mice. Multiple sclerosis (MS) is a demyelinating disease of the central

Powers, Robert

25

Differential and limited expression of mutant alleles in multiple myeloma.  

PubMed

Recent work has delineated mutational profiles in multiple myeloma and reported a median of 52 mutations per patient, as well as a set of commonly mutated genes across multiple patients. In this study, we have used deep sequencing of RNA from a subset of these patients to evaluate the proportion of expressed mutations. We find that the majority of previously identified mutations occur within genes with very low or no detectable expression. On average, 27% (range, 11% to 47%) of mutated alleles are found to be expressed, and among mutated genes that are expressed, there often is allele-specific expression where either the mutant or wild-type allele is suppressed. Even in the absence of an overall change in gene expression, the presence of differential allelic expression within malignant cells highlights the important contribution of RNA-sequencing in identifying clinically significant mutational changes relevant to our understanding of myeloma biology and also for therapeutic applications. PMID:25237203

Rashid, Naim U; Sperling, Adam S; Bolli, Niccolo; Wedge, David C; Van Loo, Peter; Tai, Yu-Tzu; Shammas, Masood A; Fulciniti, Mariateresa; Samur, Mehmet K; Richardson, Paul G; Magrangeas, Florence; Minvielle, Stephane; Futreal, P Andrew; Anderson, Kenneth C; Avet-Loiseau, Herve; Campbell, Peter J; Parmigiani, Giovanni; Munshi, Nikhil C

2014-11-13

26

Multiple Differential-Amplifier MMICs Embedded in Waveguides  

NASA Technical Reports Server (NTRS)

Compact amplifier assemblies of a type now being developed for operation at frequencies of hundreds of gigahertz comprise multiple amplifier units in parallel arrangements to increase power and/or cascade arrangements to increase gains. Each amplifier unit is a monolithic microwave integrated circuit (MMIC) implementation of a pair of amplifiers in differential (in contradistinction to single-ended) configuration. Heretofore, in cascading amplifiers to increase gain, it has been common practice to interconnect the amplifiers by use of wires and/or thin films on substrates. This practice has not yielded satisfactory results at frequencies greater than 200 Hz, in each case, for either or both of two reasons: Wire bonds introduce large discontinuities. Because the interconnections are typically tens of wavelengths long, any impedance mismatches give rise to ripples in the gain-vs.-frequency response, which degrade the performance of the cascade.

Kangaslahti, Pekka; Schlecht, Erich

2010-01-01

27

Differential item functioning analysis by applying multiple comparison procedures.  

PubMed

Analysis within a Rasch measurement framework aims at development of valid and objective test score. One requirement of both validity and objectivity is that items do not show evidence of differential item functioning (DIF). A number of procedures exist for the assessment of DIF including those based on analysis of contingency tables by Mantel-Haenszel tests and partial gamma coefficients. The aim of this paper is to illustrate Multiple Comparison Procedures (MCP) for analysis of DIF relative to a variable defining a very large number of groups, with an unclear ordering with respect to the DIF effect. We propose a single step procedure controlling the false discovery rate for DIF detection. The procedure applies for both dichotomous and polytomous items. In addition to providing evidence against a hypothesis of no DIF, the procedure also provides information on subset of groups that are homogeneous with respect to the DIF effect. A stepwise MCP procedure for this purpose is also introduced. PMID:25562333

Eusebi, Paolo; Kreiner, Svend

2015-01-01

28

THY-1 Receptor Expression Differentiates Cardiosphere-Derived Cells with Divergent Cardiogenic Differentiation Potential  

PubMed Central

Summary Despite over a decade of intense research, the identity and differentiation potential of human adult cardiac progenitor cells (aCPC) remains controversial. Cardiospheres have been proposed as a means to expand aCPCs in vitro, but the identity of the progenitor cell within these 3D structures is unknown. We show that clones derived from cardiospheres could be subdivided based on expression of thymocyte differentiation antigen 1 (THY-1/CD90) into two distinct populations that exhibit divergent cardiac differentiation potential. One population, which is CD90+, expressed markers consistent with a mesenchymal/myofibroblast cell. The second clone type was CD90? and could form mature, functional myocytes with sarcomeres albeit at a very low rate. These two populations of cardiogenic clones displayed distinct cell surface markers and unique transcriptomes. Our study suggests that a rare aCPC exists in cardiospheres along with a mesenchymal/myofibroblast cell, which demonstrates incomplete cardiac myocyte differentiation. PMID:24936447

Gago-Lopez, Nuria; Awaji, Obinna; Zhang, Yiqiang; Ko, Christopher; Nsair, Ali; Liem, David; Stempien-Otero, April; MacLellan, W. Robb

2014-01-01

29

Differential Gene Expression between Sensory Neocortical Areas: Potential Roles  

E-print Network

Differential Gene Expression between Sensory Neocortical Areas: Potential Roles for Ten_m3 and Bcl6 the regions and confirmed by quantitative polymerase chain reaction 95% of the 20 genes tested. Two genes were adulthood. Retrograde tracing showed that Bcl6 is expressed in corticospinal neurons. Ten_m3 was expressed

Kreiman, Gabriel

30

Local random potentials of high differentiability to model the Landscape  

NASA Astrophysics Data System (ADS)

We generate random functions locally via a novel generalization of Dyson Brownian motion, such that the functions are in a desired differentiability class Ck, while ensuring that the Hessian is a member of the Gaussian orthogonal ensemble (other ensembles might be chosen if desired). Potentials in such higher differentiability classes (k>= 2) are required/desirable to model string theoretical landscapes, for instance to compute cosmological perturbations (e.g., k=2 for the power-spectrum) or to search for minima (e.g., suitable de Sitter vacua for our universe). Since potentials are created locally, numerical studies become feasible even if the dimension of field space is large (0D~ 10). In addition to the theoretical prescription, we provide some numerical examples to highlight properties of such potentials; concrete cosmological applications will be discussed in companion publications.

Battefeld, T.; Modi, C.

2015-03-01

31

Local random potentials of high differentiability to model the Landscape  

E-print Network

We generate random functions locally via a novel generalization of Dyson Brownian motion, such that the functions are in a desired differentiability class, while ensuring that the Hessian is a member of the Gaussian orthogonal ensemble (other ensembles might be chosen if desired). Potentials in such higher differentiability classes are required/desirable to model string theoretical landscapes, for instance to compute cosmological perturbations (e.g., smooth first and second derivatives for the power-spectrum) or to search for minima (e.g., suitable de Sitter vacua for our universe). Since potentials are created locally, numerical studies become feasible even if the dimension of field space is large (D ~ 100). In addition to the theoretical prescription, we provide some numerical examples to highlight properties of such potentials; concrete cosmological applications will be discussed in companion publications.

Thorsten Battefeld; Chirag Modi

2015-03-10

32

Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells  

PubMed Central

Pluripotent stem cells hold significant promise in regenerative medicine due to their unlimited capacity for self-renewal, and potential to differentiate into any cell type of the body. In the current study, we demonstrate that proper mitochondrial function is essential for proliferation of undifferentiated embryonic stem cells (ESCs). Attenuating mitochondrial function under self-renewing conditions makes these cells more glycolytic-dependent, and is associated with an increase in the mRNA reserves of Nanog, Oct4 and Sox2. In contrast, attenuating mitochondrial function during the first 7 days of differentiation results in normal repression of Oct4, Nanog and Sox2. However differentiation potential is compromised as revealed by abnormal transcription of multiple Hox genes. Furthermore, under differentiating conditions in which mitochondrial function is attenuated, tumorigenic cells continue to persist. Our results, therefore establish the importance of normal mitochondrial function in ESC proliferation, regulating differentiation, and preventing the emergence of tumorigenic cells during the process of differentiation. PMID:21425411

Mandal, Sudip; Lindgren, Anne G.; Srivastava, Anand S.; Clark, Amander T.; Banerjee, Utpal

2015-01-01

33

Sox9 potentiates BMP2-induced chondrogenic differentiation and inhibits BMP2-induced osteogenic differentiation.  

PubMed

Bone morphogenetic protein 2 (BMP2) is one of the key chondrogenic growth factors involved in the cartilage regeneration. However, it also exhibits osteogenic abilities and triggers endochondral ossification. Effective chondrogenesis and inhibition of BMP2-induced osteogenesis and endochondral ossification can be achieved by directing the mesenchymal stem cells (MSCs) towards chondrocyte lineage with chodrogenic factors, such as Sox9. Here we investigated the effects of Sox9 on BMP2-induced chondrogenic and osteogenic differentiation of MSCs. We found exogenous overexpression of Sox9 enhanced the BMP2-induced chondrogenic differentiation of MSCs in vitro. Also, it inhibited early and late osteogenic differentiation of MSCs in vitro. Subcutaneous stem cell implantation demonstrated Sox9 potentiated BMP2-induced cartilage formation and inhibited endochondral ossification. Mouse limb cultures indicated that BMP2 and Sox9 acted synergistically to stimulate chondrocytes proliferation, and Sox9 inhibited BMP2-induced chondrocytes hypertrophy and ossification. This study strongly suggests that Sox9 potentiates BMP2-induced MSCs chondrogenic differentiation and cartilage formation, and inhibits BMP2-induced MSCs osteogenic differentiation and endochondral ossification. Thus, exogenous overexpression of Sox9 in BMP2-induced mesenchymal stem cells differentiation may be a new strategy for cartilage tissue engineering. PMID:24551211

Liao, Junyi; Hu, Ning; Zhou, Nian; Lin, Liangbo; Zhao, Chen; Yi, Shixiong; Fan, Tingxu; Bao, Wei; Liang, Xi; Chen, Hong; Xu, Wei; Chen, Cheng; Cheng, Qiang; Zeng, Yongming; Si, Weike; Yang, Zhong; Huang, Wei

2014-01-01

34

A differential charge-transfer readout circuit for multiple output capacitive sensors  

Microsoft Academic Search

This paper presents a true differential, low-noise readout scheme for multiple output capacitive sensors. It overcomes the restrictions with multiple sense capacitors connected to a common node that is common in micromachined gyroscopes and multiple axis accelerometers. The architecture is easily integrated into a CMOS process, only requiring single ended operational amplifiers, transmission gates and capacitors. It also supports cancellation

Henrik Rödjegård; Anders Lööf

2005-01-01

35

Biophysical Characteristics Reveal Neural Stem Cell Differentiation Potential  

PubMed Central

Background Distinguishing human neural stem/progenitor cell (huNSPC) populations that will predominantly generate neurons from those that produce glia is currently hampered by a lack of sufficient cell type-specific surface markers predictive of fate potential. This limits investigation of lineage-biased progenitors and their potential use as therapeutic agents. A live-cell biophysical and label-free measure of fate potential would solve this problem by obviating the need for specific cell surface markers. Methodology/Principal Findings We used dielectrophoresis (DEP) to analyze the biophysical, specifically electrophysiological, properties of cortical human and mouse NSPCs that vary in differentiation potential. Our data demonstrate that the electrophysiological property membrane capacitance inversely correlates with the neurogenic potential of NSPCs. Furthermore, as huNSPCs are continually passaged they decrease neuron generation and increase membrane capacitance, confirming that this parameter dynamically predicts and negatively correlates with neurogenic potential. In contrast, differences in membrane conductance between NSPCs do not consistently correlate with the ability of the cells to generate neurons. DEP crossover frequency, which is a quantitative measure of cell behavior in DEP, directly correlates with neuron generation of NSPCs, indicating a potential mechanism to separate stem cells biased to particular differentiated cell fates. Conclusions/Significance We show here that whole cell membrane capacitance, but not membrane conductance, reflects and predicts the neurogenic potential of human and mouse NSPCs. Stem cell biophysical characteristics therefore provide a completely novel and quantitative measure of stem cell fate potential and a label-free means to identify neuron- or glial-biased progenitors. PMID:21980464

Mulhall, Hayley J.; Marchenko, Steve A.; Hoettges, Kai F.; Estrada, Laura C.; Lee, Abraham P.; Hughes, Michael P.; Flanagan, Lisa A.

2011-01-01

36

Communication: Separable potential energy surfaces from multiplicative artificial neural networks  

NASA Astrophysics Data System (ADS)

We present a potential energy surface fitting scheme based on multiplicative artificial neural networks. It has the sum of products form required for efficient computation of the dynamics of multidimensional quantum systems with the multi configuration time dependent Hartree method. Moreover, it results in analytic potential energy matrix elements when combined with quantum dynamics methods using Gaussian basis functions, eliminating the need for a local harmonic approximation. Scaling behavior with respect to the complexity of the potential as well as the requested accuracy is discussed.

Koch, Werner; Zhang, Dong H.

2014-07-01

37

Communication: Separable potential energy surfaces from multiplicative artificial neural networks  

SciTech Connect

We present a potential energy surface fitting scheme based on multiplicative artificial neural networks. It has the sum of products form required for efficient computation of the dynamics of multidimensional quantum systems with the multi configuration time dependent Hartree method. Moreover, it results in analytic potential energy matrix elements when combined with quantum dynamics methods using Gaussian basis functions, eliminating the need for a local harmonic approximation. Scaling behavior with respect to the complexity of the potential as well as the requested accuracy is discussed.

Koch, Werner, E-mail: wkoch@thethirdrock.net; Zhang, Dong H. [State Key Laboratory of Molecular Reaction Dynamics and Center for Theoretical Computational Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian (China)

2014-07-14

38

Vascular Calcifying Progenitor Cells Possess Bidirectional Differentiation Potentials  

PubMed Central

Vascular calcification is an advanced feature of atherosclerosis for which no effective therapy is available. To investigate the modulation or reversal of calcification, we identified calcifying progenitor cells and investigated their calcifying/decalcifying potentials. Cells from the aortas of mice were sorted into four groups using Sca-1 and PDGFR? markers. Sca-1+ (Sca-1+/PDGFR?+ and Sca-1+/PDGFR??) progenitor cells exhibited greater osteoblastic differentiation potentials than Sca-1? (Sca-1?/PDGFR?+ and Sca-1?/PDGFR??) progenitor cells. Among Sca-1+ progenitor populations, Sca-1+/PDGFR?? cells possessed bidirectional differentiation potentials towards both osteoblastic and osteoclastic lineages, whereas Sca-1+/PDGFR?+ cells differentiated into an osteoblastic lineage unidirectionally. When treated with a peroxisome proliferator activated receptor ? (PPAR?) agonist, Sca-1+/PDGFR?? cells preferentially differentiated into osteoclast-like cells. Sca-1+ progenitor cells in the artery originated from the bone marrow (BM) and could be clonally expanded. Vessel-resident BM-derived Sca-1+ calcifying progenitor cells displayed nonhematopoietic, mesenchymal characteristics. To evaluate the modulation of in vivo calcification, we established models of ectopic and atherosclerotic calcification. Computed tomography indicated that Sca-1+ progenitor cells increased the volume and calcium scores of ectopic calcification. However, Sca-1+/PDGFR?? cells treated with a PPAR? agonist decreased bone formation 2-fold compared with untreated cells. Systemic infusion of Sca-1+/PDGFR?? cells into Apoe?/? mice increased the severity of calcified atherosclerotic plaques. However, Sca-1+/PDGFR?? cells in which PPAR? was activated displayed markedly decreased plaque severity. Immunofluorescent staining indicated that Sca-1+/PDGFR?? cells mainly expressed osteocalcin; however, activation of PPAR? triggered receptor activator for nuclear factor-?B (RANK) expression, indicating their bidirectional fate in vivo. These findings suggest that a subtype of BM-derived and vessel-resident progenitor cells offer a therapeutic target for the prevention of vascular calcification and that PPAR? activation may be an option to reverse calcification. PMID:23585735

Lee, Ho-Jae; Song, Myung-Kang; Seo, Ji-Yun; Bae, Yeon-Hee; Kim, Ju-Young; Lee, Hae-Young; Lee, Whal; Koo, Bon-Kwon; Oh, Byung-Hee; Park, Young-Bae; Kim, Hyo-Soo

2013-01-01

39

Bioenergetics and mitochondrial transmembrane potential during differentiation of cultured osteoblasts  

NASA Technical Reports Server (NTRS)

To evaluate the relationship between osteoblast differentiation and bioenergetics, cultured primary osteoblasts from fetal rat calvaria were grown in medium supplemented with ascorbate to induce differentiation. Before ascorbate treatment, the rate of glucose consumption was 320 nmol. h(-1). 10(6) cells(-1), respiration was 40 nmol. h(-1). 10(6) cells(-1), and the ratio of lactate production to glucose consumption was approximately 2, indicating that glycolysis was the main energy source for immature osteoblasts. Ascorbate treatment for 14 days led to a fourfold increase in respiration, a threefold increase in ATP production, and a fivefold increase in ATP content compared with that shown in immature cells. Confocal imaging of mitochondria stained with a transmembrane potential-sensitive vital dye showed that mature cells possessed abundant amounts of high-transmembrane-potential mitochondria, which were concentrated near the culture medium-facing surface. Acute treatment of mature osteoblasts with metabolic inhibitors showed that the rate of glycolysis rose to maintain the cellular energy supply constant. Thus progressive differentiation coincided with changes in cellular metabolism and mitochondrial activity, which are likely to play key roles in osteoblast function.

Komarova, S. V.; Ataullakhanov, F. I.; Globus, R. K.

2000-01-01

40

Multiple bit differential detection of offset quadrature phase-shift-keying  

NASA Technical Reports Server (NTRS)

Analogous to multiple symbol differential detectionof quadrature phase-shift-keying (QPSK), a multiple bit differential detection scheme is described for offset QPSK that also exhibits continuous improvement in performance with increasing observation interval. Being derived from maximum-likelihood (ML) considerations, the proposed scheme is purported to be the most power efficient scheme for such a modulation and detection method. Extension of the results to shaped offset QPSK is also possible.

Simon, M.

2003-01-01

41

Stem cells are captivating because they have the potential to make multiple cell types yet maintain their undifferentiated  

E-print Network

1575 Stem cells are captivating because they have the potential to make multiple cell types yet maintain their undifferentiated state. Recent studies of Drosophila and mammalian neural stem cells have shed light on how stem cells regulate self-renewal versus differentiation and have revealed

Doe, Chris

42

Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients  

PubMed Central

The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls. PMID:23401793

Messinis, L.; Kosmidis, M. H.; Vlahou, C.; Malegiannaki, A. C.; Gatzounis, G.; Dimisianos, N.; Karra, A.; Kiosseoglou, G.; Gourzis, P.; Papathanasopoulos, P.

2013-01-01

43

A study of impulsive multiterm fractional differential equations with single and multiple base points and applications.  

PubMed

We discuss the existence and uniqueness of solutions for initial value problems of nonlinear singular multiterm impulsive Caputo type fractional differential equations on the half line. Our study includes the cases for a single base point fractional differential equation as well as multiple base points fractional differential equation. The asymptotic behavior of solutions for the problems is also investigated. We demonstrate the utility of our work by applying the main results to fractional-order logistic models. PMID:24578623

Liu, Yuji; Ahmad, Bashir

2014-01-01

44

Differential Gene Expression in the Siphonophore Nanomia bijuga (Cnidaria) Assessed with Multiple Next-  

E-print Network

Differential Gene Expression in the Siphonophore Nanomia bijuga (Cnidaria) Assessed with Multiple polyps and swimming medusae in the siphonophore Nanomia bijuga (Cnidaria) with a hybrid long (Cnidaria) Assessed with Multiple Next-Generation Sequencing Workflows. PLoS ONE 6(7): e22953. doi:10

Dunn, Casey

45

Multiple Hypnotizabilities: Differentiating the Building Blocks of Hypnotic Response  

ERIC Educational Resources Information Center

Although hypnotizability can be conceptualized as involving component subskills, standard measures do not differentiate them from a more general unitary trait, partly because the measures include limited sets of dichotomous items. To overcome this, the authors applied full-information factor analysis, a sophisticated analytic approach for…

Woody, Erik Z.; Barnier, Amanda J.; McConkey, Kevin M.

2005-01-01

46

Differential Proteomics Reveals Multiple Components in Retrogradely Transported  

E-print Network

differential proteomics ap- proach in the freshwater mollusk Lymnaea stagnalis. This invertebrate model nervous injury-correlated retro- gradely transported proteins in nerves of the mollusk Lymnaea. A comprehensive of RGP51 expression by RNA interference inhibits regener- ative outgrowth of adult Lymnaea neurons

Fainzilber, Michael

47

Multiple sclerosis at menopause: Potential neuroprotective effects of estrogen.  

PubMed

Multiple sclerosis (MS) is an autoimmune demyelinating and neurodegenerative condition of the central nervous system that preferentially afflicts women more than men. Low estrogen states such as menopause and the postpartum period favor exacerbations of multiple sclerosis in women with the disease. Existing and emerging evidence suggests a role for estrogen in the alleviation of symptoms and reversal of pathology associated with MS. While clinical evidence is sparse regarding the benefit of estrogen therapy for women at risk for MS exacerbations, scientific data demonstrates that estrogen potentiates numerous neuroprotective effects on the central nervous system (CNS). Estrogens play a wide range of roles involved in MS disease pathophysiology, including increasing antiinflammatory cytokines, decreasing demyelination, and enhancing oxidative and energy producing processes in CNS cells. PMID:25544310

Christianson, Mindy S; Mensah, Virginia A; Shen, Wen

2015-02-01

48

System for measuring multiphase flow using multiple pressure differentials  

DOEpatents

An improved method and system for measuring a multi-phase flow in a pressure flow meter. An extended throat venturi is used and pressure of the multi-phase flow is measured at three or more positions in the venturi, which define two or more pressure differentials in the flow conduit. The differential pressures are then used to calculate the mass flow of the gas phase, the total mass flow, and the liquid phase. The system for determining the mass flow of the high void fraction fluid flow and the gas flow includes taking into account a pressure drop experienced by the gas phase due to work performed by the gas phase in accelerating the liquid phase.

Fincke, James R. (Idaho Falls, ID)

2003-01-01

49

Identifying potential programs and platforms to deliver multiple micronutrient interventions.  

PubMed

This article reviews the potential of four broad types of platforms, health, agriculture, market-based, and social protection programs, to deliver multiple micronutrient (MMN) interventions (supplementation, fortification, and dietary modification). We assessed the platforms' potential based on seven performance criteria related to programs within these platforms: 1) targeting, 2) efficacy of interventions, 3) quality of implementation, 4) utilization, 5) impact, 6) coverage, and 7) sustainability. We highlight one type of program per platform to illustrate strengths and weaknesses for delivering MMN interventions, identify critical knowledge gaps, and highlight what is needed to increase effectiveness for delivering MMN interventions. We found that all four platforms have the potential to effectively deliver MMN interventions if the following key program elements are addressed: 1) strong behavior change communication strategies to increase demand and proper utilization of services/products; 2) supply side interventions to ensure consistent availability of high quality interventions, products, and well-trained staff; 3) rigorous evaluations of effectiveness, quality of delivery, and impact pathways to generate best practices for replication and scale-up; and 4) timely dissemination of evaluation results to ensure use by program implementers and policy makers. The diversification of delivery platforms, which simultaneously addresses multiple determinants of MMN deficiencies and expands coverage, is needed to accelerate progress in reducing MMN deficiencies. PMID:22131548

Olney, Deanna K; Rawat, Rahul; Ruel, Marie T

2012-01-01

50

Differential Diagnosis, Clinical Features, and Prognosis of Multiple Sclerosis  

Microsoft Academic Search

The diagnosis and prognosis of multiple sclerosis (MS) has changed dramatically over the years from the first descriptions\\u000a from St. Lidwina of Schiedam (1380–1433) and Augustus D’Este (grandson of George III) between 1822 and 1848 to the pathological\\u000a descriptions of Cruveilhier (1829–1842) and Carswell (1838). Serious study and synthesis of clinical and pathological human\\u000a MS began with the work of

Michael J. Olek

51

Arachidonic acid-dependent gene regulation during preadipocyte differentiation controls adipocyte potential[S  

PubMed Central

Arachidonic acid (AA) is a major PUFA that has been implicated in the regulation of adipogenesis. We examined the effect of a short exposure to AA at different stages of 3T3-L1 adipocyte differentiation. AA caused the upregulation of fatty acid binding protein 4 (FABP4/aP2) following 24 h of differentiation. This was mediated by the prostaglandin F2? (PGF2?), as inhibition of cyclooxygenases or PGF2? receptor signaling counteracted the AA-mediated aP2 induction. In addition, calcium, protein kinase C, and ERK are all key elements of the pathway through which AA induces the expression of aP2. We also show that treatment with AA during the first 24 h of differentiation upregulates the expression of the transcription factor Fos-related antigen 1 (Fra-1) via the same pathway. Finally, treatment with AA for 24 h at the beginning of the adipocyte differentiation is sufficient to inhibit the late stages of adipogenesis through a Fra-1-dependent pathway, as Fra-1 knockdown rescued adipogenesis. Our data show that AA is able to program the differentiation potential of preadipocytes by regulating gene expression at the early stages of adipogenesis. PMID:25325755

Nikolopoulou, Evanthia; Papacleovoulou, Georgia; Jean-Alphonse, Frederic; Grimaldi, Giulia; Parker, Malcolm G.; Hanyaloglu, Aylin C.; Christian, Mark

2014-01-01

52

Joint analysis of differential gene expression in multiple studies using correlation motifs.  

PubMed

The standard methods for detecting differential gene expression are mostly designed for analyzing a single gene expression experiment. When data from multiple related gene expression studies are available, separately analyzing each study is not ideal as it may fail to detect important genes with consistent but relatively weak differential signals in multiple studies. Jointly modeling all data allows one to borrow information across studies to improve the analysis. However, a simple concordance model, in which each gene is assumed to be differential in either all studies or none of the studies, is incapable of handling genes with study-specific differential expression. In contrast, a model that naively enumerates and analyzes all possible differential patterns across studies can deal with study-specificity and allow information pooling, but the complexity of its parameter space grows exponentially as the number of studies increases. Here, we propose a correlation motif approach to address this dilemma. This approach searches for a small number of latent probability vectors called correlation motifs to capture the major correlation patterns among multiple studies. The motifs provide the basis for sharing information among studies and genes. The approach has flexibility to handle all possible study-specific differential patterns. It improves detection of differential expression and overcomes the barrier of exponential model complexity. PMID:25143368

Wei, Yingying; Tenzen, Toyoaki; Ji, Hongkai

2015-01-01

53

Multiple Accelerating Potential SEM Microanalysis of Individual Atmospheric Particles (Invited)  

NASA Astrophysics Data System (ADS)

There are many significant applications of individual micro- or nano-particle characterization in aerosol and atmospheric sciences, as recent AGU sessions and topical meetings of organizations like the Microbeam Analysis Society have shown. Interpreting the results of individual particle analyses is complicated by the complexity of the matrix corrections involved and the compositional variability of the particles themselves. Even nano-particles can be composites of multiple phases. And due to their large surface areas, particle properties can be dominated by their surface coatings or agglomerations. One way to efficiently characterize such multi-phase objects (for particles larger than ~100 nm) is to utilize multiple accelerating potential (MAP) imaging and x-ray analysis in a high-resolution SEM. Changing the electron beam energy in several steps from 15-20 down to 1-3 keV emphasizes surface features in the electron imaging and reduces the analytical penetration from the µm to nm range. Existing thin-film algorithmic and Monte Carlo microprobe correction procedures can be adapted to correct the analytical data for particle geometric effects. The compositions of surface layers and under-layers can be separated and accurately determined. The results of this non-destructive method compares well in both surface sensitivity and accuracy to other surface-microanalytical techniques involving ion sputtering depth profiling. We have used MAP-SEM analysis to determine the thickness of surface layers thinner than 1 nm and the composition of multi-element surface coatings less than 10 nm thick. We will show examples of multiple accelerating potential analyses for the characterization of complex 1-10 µm atmospheric particles and discuss the practical implementation of algorithmic and Monte Carlo corrections for particle x-ray emission data.

Armstrong, J. T.

2009-12-01

54

Habitat differentiation within the large-carnivore community of Norway's multiple-use landscapes  

Microsoft Academic Search

Summary 1. The re-establishment of large carnivores in Norway has led to increased conflicts and the adoption of regional zoning for these predators. When planning the future distribution of large car- nivores, it is important to consider details of their potential habitat tolerances and strength of inter- specific differentiation. We studied differentiation in habitat and kill sites within the large-carnivore

Roel May; Jiska van Dijk; Petter Wabakken; Jon E. Swenson; John D. C. Linnell; Barbara Zimmermann; John Odden; Hans C. Pedersen; Reidar Andersen; Arild Landa

2008-01-01

55

Multiple Component Event-Related Potential (mcERP) Estimation  

NASA Technical Reports Server (NTRS)

We show how model-based estimation of the neural sources responsible for transient neuroelectric signals can be improved by the analysis of single trial data. Previously, we showed that a multiple component event-related potential (mcERP) algorithm can extract the responses of individual sources from recordings of a mixture of multiple, possibly interacting, neural ensembles. McERP also estimated single-trial amplitudes and onset latencies, thus allowing more accurate estimation of ongoing neural activity during an experimental trial. The mcERP algorithm is related to informax independent component analysis (ICA); however, the underlying signal model is more physiologically realistic in that a component is modeled as a stereotypic waveshape varying both in amplitude and onset latency from trial to trial. The result is a model that reflects quantities of interest to the neuroscientist. Here we demonstrate that the mcERP algorithm provides more accurate results than more traditional methods such as factor analysis and the more recent ICA. Whereas factor analysis assumes the sources are orthogonal and ICA assumes the sources are statistically independent, the mcERP algorithm makes no such assumptions thus allowing investigators to examine interactions among components by estimating the properties of single-trial responses.

Knuth, K. H.; Clanton, S. T.; Shah, A. S.; Truccolo, W. A.; Ding, M.; Bressler, S. L.; Trejo, L. J.; Schroeder, C. E.; Clancy, Daniel (Technical Monitor)

2002-01-01

56

Differential ontogeny of multiple opioid receptors (mu, delta, and kappa)  

SciTech Connect

We investigated the postnatal ontogeny of opioid receptors in rat brain under assay conditions which, when combined with computerized analysis, effectively reflect the developmental profile of high affinity binding to mu, delta, and kappa subpopulations. Concentrations of mu sites were assessed with the selective ligand /sup 3/H-(D-ala2,mePhe4,gly-ol5)enkephalin (DAGO). The other two sites were analyzed in binding assays with less selective radioligands but in the presence of specific unlabeled ligands which suppress cross-reactivity. We utilized /sup 3/H-(D-ala2,D-leu5)enkephalin (DADL) in the presence of 10 nM DAGO to label delta sites and /sup 3/H-ethylketocyclazocine (EKC) in the presence of 100 nM DADL + 100 nM (D-ala2,mePhe4,Met(0)ol5)enkephalin to detect kappa receptors. After birth, the density (femtomoles per milligram of wet weight) of mu sites declined for several days and then rose sharply over the next 2 weeks, increasing 2-fold by adulthood. Delta (delta) sites appeared in the second week postnatal and increased more than 8-fold in the next 2 weeks. Levels of kappa receptors were relatively low at birth and increased slowly (2-fold, overall). Computerized analyses of binding data revealed that DAGO and DADL were binding to single populations of sites throughout the postnatal period. DAGO and EKC affinities did not fluctuate in this period, whereas DADL affinities were low for the first week and then rose to adult levels. In summary, mu, kappa, and delta receptors exhibit differential postnatal developmental profiles. The former two are present at birth, whereas the latter appears in the second week. The postnatal increase for all three sites appear to be preceded by the previously demonstrated emergence of opioid peptides.

Spain, J.W.; Roth, B.L.; Coscia, C.J.

1985-03-01

57

p53 abnormalities and potential therapeutic targeting in multiple myeloma.  

PubMed

p53 abnormalities are regarded as an independent prognostic marker in multiple myeloma. Patients harbouring this genetic anomaly are commonly resistant to standard therapy. Thus, various p53 reactivating agents have been developed in order to restore its tumour suppressive abilities. Small molecular compounds, especially, have gained popularity in its efficacy against myeloma cells. For instance, promising preclinical results have steered both nutlin-3 and PRIMA-1 into phase I/II clinical trials. This review summarizes different modes of p53 inactivation in myeloma and highlights the current p53-based therapies that are being utilized in the clinic. Finally, we discuss the potential and promise that the novel small molecules possess for clinical application in improving the treatment outcome of myeloma. PMID:25028664

Teoh, P J; Chng, W J

2014-01-01

58

Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation  

PubMed Central

Purpose The sigma-2 (?2) receptor is a potential biomarker of proliferative status of solid tumors. Specific synthetic probes using N-substituted-9-azabicyclo[3.3.1]nonan-3?-yl carbamate analogs have been designed and implemented for experimental cancer diagnosis and therapy. Procedures We employed the fluorescently-labeled ?2 receptor probe, SW120, to evaluate ?2 receptor expression in human stem cells (SC), including: bone marrow stromal (BMSC), neural progenitor (NPC), amniotic fluid (AFSC), hematopoetic (HSC) and embryonic stem cells (ESC). We concurrently evaluated the intensity of SW120 and 5-ethynyl-2?-deoxyuridine (EdU) relative to passage number and multipotency. Results We substantiated significantly higher ?2 receptor density among proliferating SC relative to lineage-restricted cell types. Additionally, cellular internalization of the ?2 receptor in SC was consistent with receptor-mediated endocytosis and confocal microscopy indicated SW120 specific co-localization with a fluorescent marker of lysosomes in all SC imaged. Conclusion These results suggest that ?2 receptors may serve to monitor stem cell differentiation in future experimental studies. PMID:21614680

Haller, Jodi L.; Panyutin, Irina; Chaudhry, Aneeka; Zeng, Chenbo; Mach, Robert H.; Frank, Joseph A.

2011-01-01

59

Effects of multiple doses of organophosphates on evoked potentials in mouse diaphragm.  

PubMed

1. Male albino mice were injected s.c. with an organophosphate (mipafox, ecothiopate or paraoxon). Treatments were either a single injection or multiple daily injections with lower doses for 5 or 8 days. At 3 h after injection the activity of brain and diaphragm acetylcholinesterase and of brain neuropathy target esterase (NTE) was measured. Also measured in the diaphragm at 3 h post dose was the duration of spontaneous miniature endplate potentials (eMEPPs), recorded extracellularly. 2. At 7 and 28 days after dosing action potentials and evoked endplate potentials, produced by stimulating the phrenic nerve at 30 Hz, were recorded in diaphragm muscle. The amplitudes, time-course and latencies of these potentials were measured and the variability of latencies (jitter) was calculated. 3. Single doses of mipafox (20 mg/kg), ecothiopate (0.192 mg/kg) or paraoxon (0.415 mg/kg) in the mouse produced ca. 70% inhibition of diaphragm acetylcholinesterase at 3 h after dosing. All three OPs produced a prolongation of the half-decay times of eMEPPs. 4. All three OPs in the above single doses produced increased muscle action potential (postjunctional) jitter but only mipafox produced an increase in endplate potential (prejunctional) jitter. Mipafox in a slightly reduced single dose (17.5 mg/kg) had no effect on prejunctional or postjunctional jitter. 5. Multiple dosing with mipafox (8 mg/kg daily for 5 days) increased both postjunctional and prejunctional jitter at both 7 and 28 days after the end of dosing. After multiple dosing with mipafox (5 mg/kg daily for 5 days) postjunctional (but not prejunctional) jitter was increased. Multiple doses of paraoxon (0.166 mg/kg daily for 5 days) or ecothiopate (0.76 mg/kg daily for 5 days) increased prejunctional and postjunctional jitter. 6. Depending on the dosing regime, all three OPs tested were capable of increasing both prejunctional and postjunctional jitter. Neither ecothiopate nor paraoxon inhibited NTE, so this prejunctional effect is not likely to be related to 'classical' OP-induced delayed neuropathy. The prejunctional effects may be related to long-term inhibition of acetylcholinesterase and the triggering mechanism for increase in prejunctional jitter may involve a relationship between the inhibition of acetylcholinesterase and the time for which it is inhibited. The differences between the time-courses of increases in prejunctional and postjunctional jitter and the differential effects of the different multiple dosing regimes indicate that it is likely that the triggering relationship between enzyme inhibition and time is different for prejunctional and postjunctional effects. PMID:9051411

Kelly, S S; de Blaquière, G E; Williams, F M; Blain, P G

1997-02-01

60

Differentiation between dexamethasone and betamethasone in a mixture using multiple mass spectrometry  

Microsoft Academic Search

The objective of this study was to provide LC and GC–multiple mass spectrometry (MSn) data in positive and negative ion modes to prove the distinction between dexamethasone and betamethasone in a mixture of both components. Using GC–MS, the differentiation was based on a difference in the ratio of the ion traces of the two chromatographic peaks of the ? and

K De Wasch; H. F De Brabander; M Van de Wiele; J Vercammen; D Courtheyn; S Impens

2001-01-01

61

Identification of Differential Item Functioning in Multiple-Group Settings: A Multivariate Outlier Detection Approach  

ERIC Educational Resources Information Center

We focus on the identification of differential item functioning (DIF) when more than two groups of examinees are considered. We propose to consider items as elements of a multivariate space, where DIF items are outlying elements. Following this approach, the situation of multiple groups is a quite natural case. A robust statistics technique is…

Magis, David; De Boeck, Paul

2011-01-01

62

Control of cell multiplication and differentiation of preadipocyte. D.D.  

E-print Network

cells of the preadipocyte clonal line Obl7) grown and/or maintained in serum-free hormoneSummaries Control of cell multiplication and differentiation of preadipocyte. D.D. Gaillard, R gland was required to support exponential growth of rodent adipose precursor #12;cells in the presence

Boyer, Edmond

63

Multiple-symbol differential detection of APSK based on MAP criterion  

Microsoft Academic Search

The multiple-symbol differential detection scheme based on the MAP criterion is adopted to APSK. The decision rule to estimate the transmitted signals is constructed theoretically which includes the terms of the channel noise power. The symbol error rate (SER) performance of 16APSK under the decision rule is evaluated. It is confirmed that the performance shows good approach to that of

Masanobu MACHIDA; Shiro HANDA; Shinjiro OSHITA

1998-01-01

64

Application of automatic differentiation to trajectory optimization via direct multiple shooting  

NASA Astrophysics Data System (ADS)

Automatic differentiation, also called computational differentiation and algorithmic differentiation, is the process of computing the derivatives or Taylor series of functions from the computer source code implementing the functions. To date, general-purpose trajectory optimization codes have relied on finite-differencing to compute the gradients needed by the nonlinear programming (NLP) algorithms within the codes. These codes typically support the selection of an arbitrary objective and constraint set from a library of a few hundred output variables. The use of automatic differentiation in these trajectory optimization programs can provide objective and constraint gradients to the same precision as the underlying functions without requiring the generation of hundreds of analytic derivative expressions by hand or via symbolic algebra packages. This work combines automatic differentiation with a direct multiple shooting method and uses the resulting method to solve a pair of example problems. The first is the well-known lunar launch problem, while the second is a launch vehicle ascent problem similar in complexity to that which would be computed by a program such as the Program to Optimize Simulated Trajectories (POST) for use in vehicle design studies. Results include comparisons of convergence behavior of the NLP problem and solution accuracy. Tests comparing the use of Euler angles versus quaternion elements as control variables demonstrate the versatility of automatic differentiation. For loose convergence levels automatic differentiation provided faster convergence than finite differencing on the launcher ascent problem. For tight accuracy requirements, automatic differentiation resulted in fewer major iterations on the lunar launch problem.

Garza, David Marcelo

2003-10-01

65

Differentially Variable Component Analysis (dVCA): Identifying Multiple Evoked Components using Trial-to-Trial Variability  

NASA Technical Reports Server (NTRS)

Electric potentials and magnetic fields generated by ensembles of synchronously active neurons in response to external stimuli provide information essential to understanding the processes underlying cognitive and sensorimotor activity. Interpreting recordings of these potentials and fields is difficult as each detector records signals simultaneously generated by various regions throughout the brain. We introduce the differentially Variable Component Analysis (dVCA) algorithm, which relies on trial-to-trial variability in response amplitude and latency to identify multiple components. Using simulations we evaluate the importance of response variability to component identification, the robustness of dVCA to noise, and its ability to characterize single-trial data. Finally, we evaluate the technique using visually evoked field potentials recorded at incremental depths across the layers of cortical area VI, in an awake, behaving macaque monkey.

Knuth, Kevin H.; Shah, Ankoor S.; Truccolo, Wilson; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.

2003-01-01

66

Multiple organ failure. Pathophysiology and potential future therapy.  

PubMed Central

Multiple organ failure (MOF) has reached epidemic proportions in most intensive care units and is fast becoming the most common cause of death in the surgical intensive care unit. Furthermore, in spite of the development of successive generations of new and more powerful antibiotics and increasing sophisticated techniques of organ support, our ability to salvage patients once MOF has become established has not appreciably improved over the last two decades. Clearly, new therapeutic strategies aimed at preventing or limiting the development of the physiologic abnormalities that induce organ failure are needed to improve survival in these critically ill patients. Based on our rapidly increasing knowledge of the mechanisms of MOF and the fruits of molecular biology, a number of new therapeutic approaches are in various stages of development. To effectively use these new therapeutic options as they become available, it is necessary to have a clear understanding of the pathophysiology of MOF. Thus, the goals of this review are to integrate the vast amount of new information on the basic biology of MOF and to focus special attention on the potential therapeutic consequences of these recent advances in our understanding of this complex and perplexing syndrome. PMID:1503516

Deitch, E A

1992-01-01

67

Exact differential and integral constraints for the Pauli potential in the pair density functional theory  

NASA Astrophysics Data System (ADS)

In the ground state the pair density n can be determined by solving a single auxiliary equation of a two-particle problem. Exact differential and integral constraints for the Pauli potential of the effective potential of the two-particle equation are presented. The constraints are derived using the differential virial theorem and the Hiller-Sucher-Feinberg identity.

Nagy, Á.; Amovilli, C.

2009-02-01

68

On the convexity of the multiplicative version of Karmarkar's potential function  

Microsoft Academic Search

Karmarkar's potential function is quasi-convex, but not convex. This note investigates the multiplicative version of the potential function, and shows that it is not necessarily convex in general, but is strictly convex when the corresponding feasible region is bounded. This implies that the multiplicative version of the potential function in Karmarkar's algorithm is convex, since it works on a simplex.

Hiroshi Imai

1988-01-01

69

Differential Activities of Thalidomide and Isoprenoid Biosynthetic Pathway Inhibitors in Multiple Myeloma Cells  

PubMed Central

Thalidomide has emerged as an effective agent for treating multiple myeloma, however the precise mechanism of action remains unknown. Agents known to target the isoprenoid biosynthetic pathway (IBP) can have cytotoxic effects in myeloma cells. The interactions between thalidomide and IBP inhibitors in human multiple myeloma cells were evaluated. Enhanced cytotoxicity and induction of apoptosis was observed in RPMI-8226 cells. Examination of intracellular levels of farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate (GGPP) revealed a wide variance in basal levels and response to IBP inhibitors. These findings provide a mechanism for the differential sensitivity of myeloma cells to pharmacologic manipulation of the IBP. PMID:19646757

Holstein, Sarah A.; Tong, Huaxiang; Hohl, Raymond J.

2013-01-01

70

Single- and Multiple-Objective Optimization with Differential Evolution and Neural Networks  

NASA Technical Reports Server (NTRS)

Genetic and evolutionary algorithms have been applied to solve numerous problems in engineering design where they have been used primarily as optimization procedures. These methods have an advantage over conventional gradient-based search procedures became they are capable of finding global optima of multi-modal functions and searching design spaces with disjoint feasible regions. They are also robust in the presence of noisy data. Another desirable feature of these methods is that they can efficiently use distributed and parallel computing resources since multiple function evaluations (flow simulations in aerodynamics design) can be performed simultaneously and independently on ultiple processors. For these reasons genetic and evolutionary algorithms are being used more frequently in design optimization. Examples include airfoil and wing design and compressor and turbine airfoil design. They are also finding increasing use in multiple-objective and multidisciplinary optimization. This lecture will focus on an evolutionary method that is a relatively new member to the general class of evolutionary methods called differential evolution (DE). This method is easy to use and program and it requires relatively few user-specified constants. These constants are easily determined for a wide class of problems. Fine-tuning the constants will off course yield the solution to the optimization problem at hand more rapidly. DE can be efficiently implemented on parallel computers and can be used for continuous, discrete and mixed discrete/continuous optimization problems. It does not require the objective function to be continuous and is noise tolerant. DE and applications to single and multiple-objective optimization will be included in the presentation and lecture notes. A method for aerodynamic design optimization that is based on neural networks will also be included as a part of this lecture. The method offers advantages over traditional optimization methods. It is more flexible than other methods in dealing with design in the context of both steady and unsteady flows, partial and complete data sets, combined experimental and numerical data, inclusion of various constraints and rules of thumb, and other issues that characterize the aerodynamic design process. Neural networks provide a natural framework within which a succession of numerical solutions of increasing fidelity, incorporating more realistic flow physics, can be represented and utilized for optimization. Neural networks also offer an excellent framework for multiple-objective and multi-disciplinary design optimization. Simulation tools from various disciplines can be integrated within this framework and rapid trade-off studies involving one or many disciplines can be performed. The prospect of combining neural network based optimization methods and evolutionary algorithms to obtain a hybrid method with the best properties of both methods will be included in this presentation. Achieving solution diversity and accurate convergence to the exact Pareto front in multiple objective optimization usually requires a significant computational effort with evolutionary algorithms. In this lecture we will also explore the possibility of using neural networks to obtain estimates of the Pareto optimal front using non-dominated solutions generated by DE as training data. Neural network estimators have the potential advantage of reducing the number of function evaluations required to obtain solution accuracy and diversity, thus reducing cost to design.

Rai, Man Mohan

2006-01-01

71

Automatic differentiation for design sensitivity analysis of structural systems using multiple processors  

NASA Technical Reports Server (NTRS)

An automatic differentiation tool (ADIFOR) is incorporated into a finite element based structural analysis program for shape and non-shape design sensitivity analysis of structural systems. The entire analysis and sensitivity procedures are parallelized and vectorized for high performance computation. Small scale examples to verify the accuracy of the proposed program and a medium scale example to demonstrate the parallel vector performance on multiple CRAY C90 processors are included.

Nguyen, Duc T.; Storaasli, Olaf O.; Qin, Jiangning; Qamar, Ramzi

1994-01-01

72

Control of matric water potential by temperature differential  

NASA Technical Reports Server (NTRS)

A method for controlling relative humidity based on temperature differentials, rather than on salt solutions, is described. This method has the following advantages: (1) it does not exhibit the anomalous CO2 solution effects that we have found to occur with salt solutions; (2) humidity is continuously adjustable without sample removal; (3) circulation of the atmosphere results in short equilibration times.

Palmer, R. J. Jr; Nienow, J. A.; Friedmann, E. I.

1987-01-01

73

Induction of Multiple Immune Regulatory Pathways with Differential Impact in HCV/HIV Coinfection  

PubMed Central

Persistent viral infections including HCV, HBV, and HIV are associated with increased immune regulatory pathways including the extrinsic FoxP3+CD4+ regulatory T cells (Tregs) and intrinsic inhibitory pathways such as programed death-1 (PD-1) and cytotoxic T lymphocyte antigen-4 (CTLA-4) with potentially reversible suppression of antiviral effector T cells (1–12). Immunological consequences of viral coinfections relative to these immune regulatory pathways and their interplay are not well-defined. In this study, we examined the frequency, phenotype, and effector function of circulating T cell subsets in patients with chronic HCV and/or HIV infection, hypothesizing that HCV/HIV coinfection will result in greater immune dysregulation with pathogenetic consequences (13, 14). We show that multiple T cell inhibitory pathways are induced in HCV/HIV coinfection including FoxP3+ Tregs, PD-1, and CTLA-4 in inverse association with overall CD4 T cell frequency but not with liver function or HCV RNA titers. The inverse association between CD4 T cell frequency and their FoxP3, PD-1, or CTLA-4 expression remained significant in all subjects combined regardless of HCV and/or HIV infection, suggesting a global homeostatic mechanism to maintain immune regulation relative to CD4 T cell frequency. PD-1 blockade rescued T cell responses to HIV but not HCV without significant impact by CTLA-4 blockade in vitro. Collectively, these findings highlight complex immune interactions in viral coinfections and differential regulatory pathways influencing virus-specific T cells that are relevant in immunotherapeutic development. PMID:25071758

Cho, Hyosun; Kikuchi, Masahiro; Li, Yun; Nakamoto, Nobuhiro; Amorosa, Valerianna K.; Valiga, Mary E.; Chang, Kyong-Mi

2014-01-01

74

Inorganic phosphate regulates multiple genes during osteoblast differentiation, including Nrf2  

Microsoft Academic Search

The process of osteoblast differentiation and matrix mineralization requires a rise in alkaline phosphatase enzymatic activity resulting in the generation of free phosphate. The ability of inorganic phosphate to regulate gene transcription and cellular function represents a potentially novel extracellular signaling mechanism. Using microarray analysis we have identified a discrete set of genes that are either positively or negatively regulated

George R Beck; Elizabeth Moran; Nicole Knecht

2003-01-01

75

In silico investigations of potential anabolic treatments in multiple myeloma-induced bone disease.  

PubMed

No anabolic drugs are currently approved to treat multiple myeloma (MM)-induced bone disease and the anti-MM agent bortezomib exhibits the anabolic effects in the clinic. In this study, we focus on investigating potential anabolic treatments of MM-induced bone disease using our previously proposed MM-bone model, with the goal for clarifying the underlying molecular/cellular mechanisms. Firstly, a variety of virtual drug treatments are explored by the parametric study to clarify the anabolic-related molecular/cellular mechanisms. The real drug (i.e., bortezomib) treatments are further examined by developing an integrated model with bortezomib to validate the clarified anabolic-related molecular/cellular mechanisms. The simulated responses to the bortezomib treatments that are validated by the clinical data are consistent with the simulated responses to the virtual drug treatments. Our study clarifies that the anabolic effects in the treatment of MM-induced bone disease are associated with promoting the differentiation of bone marrow stromal cells (BMSC) and inhibiting the apoptosis of active osteoblasts, while promoting the differentiation of osteoblast precursors is instead suggested to be associated with the anti-catabolic effects. Compared with the individual anabolic therapies, the anabolic therapies that promote the differentiation of BMSC in combination with the anti-MM/anti-catabolic therapies are found to induce a greater increase in the bone volume, while the anabolic therapies that inhibit the apoptosis of active osteoblasts in combination with the anti-MM/anti-catabolic therapies induce a lower increase in the bone volume. The simulations also suggest that the direct inhibition of bortezomib on the osteoclast activity is probably a redundant mechanism. PMID:23416846

Wang, Yan; Lin, Bo

2013-07-01

76

Electrocutaneous reflexes and multimodality evoked potentials in multiple sclerosis  

Microsoft Academic Search

Electrical stimulation of the digital nerves of the index finger produces changes in the EMG signal during steady voluntary contraction of the first dorsal interosseous muscle. This electrocutaneous reflex (ECR) was studied in 90 patients classified into different categories according to diagnostic criteria for multiple sclerosis. In addition, pattern reversal visual evoked responses (VER), brainstem auditory evoked responses (BAER) as

W G Friedli; P Fuhr

1990-01-01

77

Improved detection of differentially expressed genes in microarray experiments through multiple scanning and image integration  

PubMed Central

The variability of results in microarray technology is in part due to the fact that independent scans of a single hybridised microarray give spot images that are not quite the same. To solve this problem and turn it to our advantage, we introduced the approach of multiple scanning and of image integration of microarrays. To this end, we have developed specific software that creates a virtual image that statistically summarises a series of consecutive scans of a microarray. We provide evidence that the use of multiple imaging (i) enhances the detection of differentially expressed genes; (ii) increases the image homogeneity; and (iii) reveals false-positive results such as differentially expressed genes that are detected by a single scan but not confirmed by successive scanning replicates. The increase in the final number of differentially expressed genes detected in a microarray experiment with this approach is remarkable; 50% more for microarrays hybridised with targets labelled by reverse transcriptase, and 200% more for microarrays developed with the tyramide signal amplification (TSA) technique. The results have been confirmed by semi-quantitative RT–PCR tests. PMID:14627839

Romualdi, Chiara; Trevisan, Silvia; Celegato, Barbara; Costa, Germano; Lanfranchi, Gerolamo

2003-01-01

78

Multiple Sources for Cardiac Stem Cells and Their Cardiogenic Potential  

Microsoft Academic Search

\\u000a The belief that the heart is a terminally differentiated organ was a very well established notion among the scientific community\\u000a until the early 2000s, although several authors tried to challenge this dogma over the years. Nonetheless, myocyte turnover\\u000a was only accepted after the demonstration of the intense proliferation that occurs, in human hearts, acutely after myocardial\\u000a infarction. The first clues

Antonio Paolo Beltrami; Daniela Cesselli; Carlo Alberto Beltrami

79

Potential function control for multiple high-speed nonholonomic robots  

Microsoft Academic Search

Many approaches to the formation control problem for multi-robot systems have been proposed. In distributed consensus algorithm methods, and leader-follower structures the robots are explicitly assigned positions within the desired formation. By contrast, artificial potential function (APF) control generally does not specify a formation explicitly but rather drives the robots down the negative gradient of a potential field such that

Luke M. Wachter; John Murphy; Laura Ray

2008-01-01

80

Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation  

PubMed Central

This paper presents a new image segmentation method based on multiple active contours guided by differential evolution, called MACDE. The segmentation method uses differential evolution over a polar coordinate system to increase the exploration and exploitation capabilities regarding the classical active contour model. To evaluate the performance of the proposed method, a set of synthetic images with complex objects, Gaussian noise, and deep concavities is introduced. Subsequently, MACDE is applied on datasets of sequential computed tomography and magnetic resonance images which contain the human heart and the human left ventricle, respectively. Finally, to obtain a quantitative and qualitative evaluation of the medical image segmentations compared to regions outlined by experts, a set of distance and similarity metrics has been adopted. According to the experimental results, MACDE outperforms the classical active contour model and the interactive Tseng method in terms of efficiency and robustness for obtaining the optimal control points and attains a high accuracy segmentation. PMID:23983809

Cruz-Aceves, I.; Avina-Cervantes, J. G.; Lopez-Hernandez, J. M.; Rostro-Gonzalez, H.; Garcia-Capulin, C. H.; Torres-Cisneros, M.; Guzman-Cabrera, R.

2013-01-01

81

Evaluation of earthquake potential and surface deformation by Differential Interferometry  

Microsoft Academic Search

Uncertainties in the length of active faults and the styles of deformation often hamper the evaluation of seismic potentials in a region. In the area near Chiayi City of southwestern Taiwan, where historically there have been many strong earthquakes, complex fault and fold systems produced by regional tectonic forces and the subsequent deformation are frequently obscured by vegetation and anthropogenic

Jiun-Yee Yen; Kun-Shan Chen; Chung-Pai Chang; Wolfgang-Martin Boerner

2008-01-01

82

Multiple mesenteric well-differentiated liposarcoma complicated by purulent inflammation: A case report  

PubMed Central

Multiple mesenteric well-differentiated (WD) liposarcoma is an extremely rare entity. The present study describes a case of multiple mesenteric WD liposarcoma, complicated by purulent inflammation, in a 59-year-old male who presented with abdominal pain and pyrexia of unknown origin. A computed tomography scan of the abdomen revealed a large, non-encapsulated mass in the abdomino-pelvic cavity, which was characterized by two components, a main portion of fatty density and a non-adipose solid portion. A re-evaluated CT scan, performed eight days later, revealed an enlargement of the non-adipose mass. A laparotomy was performed, and numerous separated fatty nodules and masses of various sizes were identified within the mesentery of the small intestine. The histological findings were consistent with an adipocytic subtype of multiple mesenteric WD liposarcoma, with the largest of the tumors complicated by purulent inflammation. The multiplicity of these tumors and the concurrent purulent inflammation in the present case make it unique. PMID:25663908

GAO, WEI; WANG, HUAIZHOU; LIU, JINYU; WANG, FUJIANG; DONG, JIANJUN; GENG, JUNZU

2015-01-01

83

Adipogenic differentiation potential of rat adipose tissue-derived subpopulations of stromal cells.  

PubMed

Adipose-derived stromal cells (ASCs) are mostly isolated by enzymatic digestion, centrifugation and adherent growth resulting in a very heterogeneous cell population. Therefore, other cell types in the cell culture can comprise the differentiation and proliferation potential of the ASC population. Recent studies indicated that an antibody-aided isolation of distinct ASC subpopulations provides advantages over the conventional method of ASC isolation. The aim of this study was to investigate the adipogenic differentiation potential of CD29-, CD71-, CD73- and CD90-selected ASCs in vitro. The stromal vascular fraction (SVF) was obtained from rat adipose tissue by enzymatic digestion and centrifugation. Subsequently, CD29(+)-, CD71(+)-, CD73(+)- and CD90(+) cells were isolated by magnetic activated cell sorting (MACS), seeded into culture plates and differentiated into the adipogenic lineage. ASCs isolated by adherent growth only served as controls. Adipogenic differentiation was assessed by Oil Red O staining and quantification of the adiponectin and leptin concentrations in the cell culture supernatants. Statistical analysis was carried out using one-way analysis of variance (ANOVA) followed by the Scheffe's post hoc procedure. The results showed that different subpopulations with different adipogenic differentiation potentials can be isolated by the MACS procedure. The highest adipogenic differentiation potential was determined in the CD29-selected ASC population followed by the unsorted ASC population. The CD71-, CD73- and CD90-selected cells exhibited significantly the lowest adipogenic differentiation potential. In conclusion, the CD29-selected ASCs and the unsorted ASCs exhibited a similar adipogenic differentiation potential. Therefore, we do not see a clear advantage in the application of an anti-CD29-based isolation of ASCs over the conventional technique using adherent growth. However, the research on isolation/purification methods of adipogenic ASCs should continue in order to make this stem cell source even more attractive for future adipose tissue engineering applications. PMID:24947082

Gierloff, M; Petersen, L; Oberg, H-H; Quabius, E S; Wiltfang, J; Açil, Y

2014-10-01

84

Brain injury does not alter the intrinsic differentiation potential of adult neuroblasts.  

PubMed

Neuroblasts produced by the neural stem cells of the adult subventricular zone (SVZ) migrate into damaged brain areas after stroke or other brain injuries, and previous data have suggested that they generate regionally appropriate new neurons. To classify the types of neurons produced subsequent to ischemic injury, we combined BrdU or virus labeling with multiple neuronal markers to characterize new cells at different times after the induction of stroke. We show that SVZ neuroblasts give rise almost exclusively to calretinin-expressing cells in the damaged striatum, resulting in the accumulation of these cells during long term recovery after stroke. The vast majority of SVZ neuroblasts as well as newly born young and mature neurons in the damaged striatum constitutively express the transcription factor Sp8, but do not express transcription factors characteristic of medium-sized spiny neurons, the primary striatal projection neurons lost after stroke. Our results suggest that adult neuroblasts do not alter their intrinsic differentiation potential after brain injury. PMID:19386903

Liu, Fang; You, Yan; Li, Xiaosu; Ma, Tong; Nie, Yanzhen; Wei, Bin; Li, Tiejun; Lin, Huanbing; Yang, Zhengang

2009-04-22

85

Therapeutic potential of carbon monoxide in multiple sclerosis  

PubMed Central

Summary Carbon monoxide (CO) is produced during the catabolism of free haem, catalyzed by haem oxygenase (HO) enzymes, and its physiological roles include vasodilation, neurotransmission, inhibition of platelet aggregation and anti-proliferative effects on smooth muscle. In vivo preclinical studies have shown that exogenously administered quantities of CO may represent an effective treatment for conditions characterized by a dysregulated immune response. The carbon monoxide-releasing molecules (CORMs) represent a group of compounds capable of carrying and liberating controlled quantities of CO in the cellular systems. This review covers the physiological and anti-inflammatory properties of the HO/CO pathway in the central nervous system. It also discusses the effects of CORMs in preclinical models of inflammation. The accumulating data discussed herein support the possibility that CORMs may represent a novel class of drugs with disease-modifying properties in multiple sclerosis. PMID:22235993

Fagone, P; Mangano, K; Coco, M; Perciavalle, V; Garotta, G; Romao, C C; Nicoletti, F

2012-01-01

86

Detecting differentially methylated loci for multiple treatments based on high-throughput methylation data  

PubMed Central

Background Because of its important effects, as an epigenetic factor, on gene expression and disease development, DNA methylation has drawn much attention from researchers. Detecting differentially methylated loci is an important but challenging step in studying the regulatory roles of DNA methylation in a broad range of biological processes and diseases. Several statistical approaches have been proposed to detect significant methylated loci; however, most of them were designed specifically for case-control studies. Results Noticing that the age is associated with methylation level and the methylation data are not normally distributed, in this paper, we propose a nonparametric method to detect differentially methylated loci under multiple conditions with trend for Illumina Array Methylation data. The nonparametric method, Cuzick test is used to detect the differences among treatment groups with trend for each age group; then an overall p-value is calculated based on the method of combining those independent p-values each from one age group. Conclusions We compare the new approach with other methods using simulated and real data. Our study shows that the proposed method outperforms other methods considered in this paper in term of power: it detected more biological meaningful differentially methylated loci than others. PMID:24884464

2014-01-01

87

Multiple roles for HOXA3 in regulating thymus and parathyroid differentiation and morphogenesis in mouse.  

PubMed

Hoxa3 was the first Hox gene to be mutated by gene targeting in mice and is required for the development of multiple endoderm and neural crest cell (NCC)-derived structures in the pharyngeal region. Previous studies have shown that the Hoxa3 null mutant lacks third pharyngeal pouch derivatives, the thymus and parathyroids by E18.5, and organ-specific markers are absent or downregulated during initial organogenesis. Our current analysis of the Hoxa3 null mutant shows that organ-specific domains did undergo initial patterning, but the location and timing of key regional markers within the pouch, including Tbx1, Bmp4 and Fgf8, were altered. Expression of the parathyroid marker Gcm2 was initiated but was quickly downregulated and differentiation failed; by contrast, thymus markers were delayed but achieved normal levels, concurrent with complete loss through apoptosis. To determine the cell type-specific roles of Hoxa3 in third pharyngeal pouch development, we analyzed tissue-specific mutants using endoderm and/or NCC-specific Cre drivers. Simultaneous deletion with both drivers resulted in athymia at E18.5, similar to the null. By contrast, the individual tissue-specific Hoxa3 deletions resulted in small, ectopic thymi, although each had a unique phenotype. Hoxa3 was primarily required in NCCs for morphogenesis. In endoderm, Hoxa3 temporally regulated initiation of the thymus program and was required in a cell-autonomous manner for parathyroid differentiation. Furthermore, Hoxa3 was required for survival of third pharyngeal pouch-derived organs, but expression in either tissue was sufficient for this function. These data show that Hoxa3 has multiple complex and tissue-specific functions during patterning, differentiation and morphogenesis of the thymus and parathyroids. PMID:25249461

Chojnowski, Jena L; Masuda, Kyoko; Trau, Heidi A; Thomas, Kirk; Capecchi, Mario; Manley, Nancy R

2014-10-01

88

Differential expression of multiple unexpected genes during U937 cell and macrophage differentiation detected by suppressive subtractive hybridization  

Microsoft Academic Search

Objective. The objective of this study was to identify new markers of myelomonocytic differentiation using a sensitive technique that permits detection of rare differential gene expression. Suppressive subtractive hybridization (SSH) was performed between the human myelomonocytic U937 cell line and 1?, 25-dihydroxyvitamin D3 and transforming growth factor ?1 differentiated U937 cells. cDNA clones with significant increased expression in differentiated U937

Marie-Claude Gingras; Judith F Margolin

2000-01-01

89

Integrated Model of Multiple Kernel Learning and Differential Evolution for EUR/USD Trading  

PubMed Central

Currency trading is an important area for individual investors, government policy decisions, and organization investments. In this study, we propose a hybrid approach referred to as MKL-DE, which combines multiple kernel learning (MKL) with differential evolution (DE) for trading a currency pair. MKL is used to learn a model that predicts changes in the target currency pair, whereas DE is used to generate the buy and sell signals for the target currency pair based on the relative strength index (RSI), while it is also combined with MKL as a trading signal. The new hybrid implementation is applied to EUR/USD trading, which is the most traded foreign exchange (FX) currency pair. MKL is essential for utilizing information from multiple information sources and DE is essential for formulating a trading rule based on a mixture of discrete structures and continuous parameters. Initially, the prediction model optimized by MKL predicts the returns based on a technical indicator called the moving average convergence and divergence. Next, a combined trading signal is optimized by DE using the inputs from the prediction model and technical indicator RSI obtained from multiple timeframes. The experimental results showed that trading using the prediction learned by MKL yielded consistent profits. PMID:25097891

Deng, Shangkun; Sakurai, Akito

2014-01-01

90

Integrated model of multiple kernel learning and differential evolution for EUR/USD trading.  

PubMed

Currency trading is an important area for individual investors, government policy decisions, and organization investments. In this study, we propose a hybrid approach referred to as MKL-DE, which combines multiple kernel learning (MKL) with differential evolution (DE) for trading a currency pair. MKL is used to learn a model that predicts changes in the target currency pair, whereas DE is used to generate the buy and sell signals for the target currency pair based on the relative strength index (RSI), while it is also combined with MKL as a trading signal. The new hybrid implementation is applied to EUR/USD trading, which is the most traded foreign exchange (FX) currency pair. MKL is essential for utilizing information from multiple information sources and DE is essential for formulating a trading rule based on a mixture of discrete structures and continuous parameters. Initially, the prediction model optimized by MKL predicts the returns based on a technical indicator called the moving average convergence and divergence. Next, a combined trading signal is optimized by DE using the inputs from the prediction model and technical indicator RSI obtained from multiple timeframes. The experimental results showed that trading using the prediction learned by MKL yielded consistent profits. PMID:25097891

Deng, Shangkun; Sakurai, Akito

2014-01-01

91

Potential impacts of vertical cable seismic: modeling, resolution and multiple attenuation  

E-print Network

POTENTIAL IMPACTS OF VERTICAL CABLE SEISMIC: MODELING, RESOLUTION AND MULTIPLE ATTENUATION A Thesis by RYAN JUSTIN WILSON Submitted to the Office of Graduate Studies of Texas A&M University in partial fulfillment of the requirements for the degree... of MASTER OF SCIENCE May 2002 Major Subject: Geophysics POTENTIAL IMPACTS OF VERTICAL CABLE SEISMIC: MODELING, RESOLUTION AND MULTIPLE ATTENUATION A Thesis by RYAN JUSTIN WILSON Submitted to Texas A&M University in partial fulfillment of the requirements...

Wilson, Ryan Justin

2004-09-30

92

Serum lactate as a novel potential biomarker in multiple sclerosis.  

PubMed

Multiple sclerosis (MS) is a primary inflammatory demyelinating disease associated with a probably secondary progressive neurodegenerative component. Impaired mitochondrial functioning has been hypothesized to drive neurodegeneration and to cause increased anaerobic metabolism in MS. The aim of our multicentre study was to determine whether MS patients had values of circulating lactate different from those of controls. Patients (n=613) were recruited, assessed for disability and clinically classified (relapsing-remitting, secondary progressive, primary progressive) at the Catholic University of Rome, Italy (n=281), at the MS Centre Amsterdam, The Netherlands (n=158) and at the S. Camillo Forlanini Hospital, Rome, Italy (n=174). Serum lactate levels were quantified spectrophotometrically with the analyst being blinded to all clinical information. In patients with MS serum lactate was three times higher (3.04±1.26mmol/l) than that of healthy controls (1.09±0.25mmol/l, p<0.0001) and increased across clinical groups, with higher levels in cases with a progressive than with a relapsing-remitting disease course. In addition, there was a linear correlation between serum lactate levels and the expanded disability scale (EDSS) (R(2)=0.419; p<0.001). These data support the hypothesis that mitochondrial dysfunction is an important feature in MS and of particular relevance to the neurodegenerative phase of the disease. Measurement of serum lactate in MS might be a relative inexpensive test for longitudinal monitoring of "virtual hypoxia" in MS and also a secondary outcome for treatment trials aimed to improve mitochondrial function in patients with MS. PMID:24726946

Amorini, Angela M; Nociti, Viviana; Petzold, Axel; Gasperini, Claudio; Quartuccio, Esmeralda; Lazzarino, Giacomo; Di Pietro, Valentina; Belli, Antonio; Signoretti, Stefano; Vagnozzi, Roberto; Lazzarino, Giuseppe; Tavazzi, Barbara

2014-07-01

93

Cellular diversity within embryonic stem cells: pluripotent clonal sublines show distinct differentiation potential  

PubMed Central

Abstract Embryonic stem cells (ESC), derived from the early inner cell mass (ICM), are constituted of theoretically homogeneous pluripotent cells. Our study was designed to test this concept using experimental approaches that allowed characterization of progenies derived from single parental mouse ESC. Flow cytometry analysis showed that a fraction of ESC submitted to neural differentiation generates progenies that escape the desired phenotype. Live imaging of individual cells demonstrated significant variations in the capacity of parental ESC to generate neurons, raising the possibility of clonal diversity among ESC. To further substantiate this hypothesis, clonal sublines from ESC were generated by limit dilution. Transcriptome analysis of undifferentiated sublines showed marked differences in gene expression despite the fact that all clones expressed pluripotency markers. Sublines showed distinct differentiation potential, both in phenotypic differentiation assays and with respect to gene expression in embryoid bodies. Clones generated from another ESC line also showed individualities in their differentiation potential, demonstrating the wider applicability of these findings. Taken together, our observations demonstrate that pluripotent ESC consist of individual cell types with distinct differentiation potentials. These findings identify novel elements for the biological understanding of ESC and provide new tools with a major potential for their future in vitro and in vivo use. PMID:21535399

Martinez, Yannick; Béna, Frédérique; Gimelli, Stefania; Tirefort, Diderik; Dubois-Dauphin, Michel; Krause, Karl-Heinz; Preynat-Seauve, Olivier

2012-01-01

94

Voltage-controlled multiple-valued logic design using negative differential resistance devices  

NASA Astrophysics Data System (ADS)

This paper demonstrates a concise and novel voltage-controlled multiple-valued logic (MVL) design using the standard BiCMOS technique. This MVL circuit is constructed by a voltage-controlled negative differential resistance (NDR) circuit, which is integrated by the standard Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and SiGe-based heterojunction bipolar transistor (HBT). There exists a two-peak current-voltage curve by connecting two integrated MOS-HBT-NDR elements in parallel as we suitably determine the width/length ( W/ L) of the MOS devices. In particular, each peak current can be effectively modulated by the corresponding controlled voltage. Using this special characteristic, we can obtain the three logic states with arbitrary sequence at the output.

Gan, Kwang-Jow; Tsai, Cher-Shiung; Chen, Yan-Wun; Yeh, Wen-Kuan

2010-12-01

95

Regenerative medicine in multiple sclerosis: identifying pharmacological targets of adult neural stem cell differentiation.  

PubMed

Progressive axonal loss from chronic demyelination in multiple sclerosis (MS) is the key contributor to clinical decline. Failure to regenerate myelin by adult oligodendrocyte precursor cells (OPCs), a widely distributed neural stem cell population in the adult brain, is one of the major causes of axonal degeneration. In order to develop successful therapies to protect the integrity of axons in MS, it is important to identify and understand the key molecular pathways involved in myelin regeneration (remyelination) by adult OPCs. This review highlights recent findings on the critical signaling pathways associated with OPC differentiation following CNS demyelination. We discuss the role of LINGO-1, Notch, Wnt, and retinoid X receptor (RXR) signaling, and how they might be useful pharmacological targets to overcoming remyelination failure in MS. PMID:21300122

Huang, Jeffrey K; Franklin, Robin J M

2011-09-01

96

HERV-W polymorphism in chromosome X is associated with multiple sclerosis risk and with differential expression of MSRV  

PubMed Central

Background Multiple Sclerosis (MS) is an autoimmune demyelinating disease that occurs more frequently in women than in men. Multiple Sclerosis Associated Retrovirus (MSRV) is a member of HERV-W, a multicopy human endogenous retroviral family repeatedly implicated in MS pathogenesis. MSRV envelope protein is elevated in the serum of MS patients and induces inflammation and demyelination but, in spite of this pathogenic potential, its exact genomic origin and mechanism of generation are unknown. A possible link between the HERV-W copy on chromosome Xq22.3, that contains an almost complete open reading frame, and the gender differential prevalence in MS has been suggested. Results MSRV transcription levels were higher in MS patients than in controls (U-Mann–Whitney; p?=?0.004). Also, they were associated with the clinical forms (Spearman; p?=?0.0003) and with the Multiple Sclerosis Severity Score (MSSS) (Spearman; p?=?0.016). By mapping a 3 kb region in Xq22.3, including the HERV-W locus, we identified three polymorphisms: rs6622139 (T/C), rs6622140 (G/A) and rs1290413 (G/A). After genotyping 3127 individuals (1669 patients and 1458 controls) from two different Spanish cohorts, we found that in women rs6622139 T/C was associated with MS susceptibility: [?2; p?=?0.004; OR (95% CI)?=?0.50 (0.31-0.81)] and severity, since CC women presented lower MSSS scores than CT (U-Mann–Whitney; p?=?0.039) or TT patients (U-Mann–Whitney; p?=?0.031). Concordantly with the susceptibility conferred in women, rs6622139*T was associated with higher MSRV expression (U-Mann–Whitney; p?=?0.003). Conclusions Our present work supports the hypothesis of a direct involvement of HERV-W/MSRV in MS pathogenesis, identifying a genetic marker on chromosome X that could be one of the causes underlying the gender differences in MS. PMID:24405691

2014-01-01

97

Impairment of brainstem implicit learning paradigms differentiates multiple system atrophy (MSA) from idiopathic Parkinson syndrome  

PubMed Central

Objectives Learning as measured by eyeblink classical conditioning is preserved in patients with idiopathic Parkinson's disease, but severely affected in patients with progressive supranuclear palsy. We here sought to clarify whether procedural learning is impaired in multiple system atrophy (MSA), and whether it may be helpful for the differentiation of parkinsonian syndromes. Design We investigated learning using (1) eyeblink classical conditioning with a delay (interstimulus interval 0?ms) and a trace (600?ms) paradigm and (2) a serial reaction time task. Setting Participants were recruited from academic research centres. Participants 11 patients with MSA and 11 healthy controls. Results Implicit learning in eyeblink classical conditioning (acquisition of conditioned responses) as well as the serial reaction time task measures of implicit learning (reaction time change) are impaired in patients with MSA as compared with controls, whereas explicit learning as measured by the sequence recall of the serial reaction time task is relatively preserved. Analysis We hypothesise that the learning deficits of patients with MSA are due to lesions of cerebellar and connected brainstem areas. Conclusions A retrospective synopsis of these novel data on patients with MSA and groups of patients with idiopathic Parkinson's disease and progressive supranuclear palsy studied earlier suggest that eyeblink classical conditioning may contribute to the early differentiation of atypical Parkinson syndromes from idiopathic Parkinson's disease. This hypothesis should be tested in a prospective trial. PMID:24038003

von Lewinski, Friederike; Schwan, Michaela; Paulus, Walter; Trenkwalder, Claudia; Sommer, Martin

2013-01-01

98

Multisensor readout circuit using a multiple differential-input operation amplifier with pulse output  

NASA Astrophysics Data System (ADS)

In this paper, a CMOS multisensor readout circuit is presented. A multiple differential-input operational amplifier (MDI-OPA) with three distinct positive inputs and one common negative input is designed to make one of the three inputs to act as a general differential-input OPA through a built-in multiplexer. A voltage-to-current converter and a current-controlled oscillator are integrated with the MDI-OPA so that the selected analog input voltage can be used to generate a pulse output whose frequency is linearly proportional to the selected input voltage. The linearity of the transfer characteristic is at least 99.99% for input voltages below 1.44 V. An added current-offset structure is used to modify the transfer characteristic that usually varies owing to process variation. The measured output transfer characteristics of three input channels show nearly the same sensitivity of 90 Hz/mV or so with a linearity of at least 99.99% with the assistance of the current-offset mechanism.

Wang, Ruey-Lue; Fu, Chien-Cheng; Yu, Chi; Wu, Wei-De; Chuang, Yan-Tse; Lin, Chen-Fu; Liao, Hsin-Hao; Tsai, Hann-Huei; Juang, Ying-Zong

2014-01-01

99

Differentiation between multiple liver hemangiomas and liver metastases of gastrinomas: Value of enhanced MRI  

SciTech Connect

Hepatic metastases of neuroendocrine tumors are known to mimic hemangiomas on nonenhanced SE MR sequences. The usefulness of MR examination with gadolinium injection to identify lesions was prospectively evaluated. Nine patients with multiple liver metastases of gastrinomas were compared with six patients showing multiple liver hemangiomas. Patients underwent unenhanced T2-weighted SE, T1-weighted SE, and FLASH sequences, followed by enhanced sequential FLASH sequences and a 5 min delayed T1-weighted SE sequence. On T2-weighted SE sequence, all hemangiomas displayed the same typical morphology as a sharply defined, homogeneous, high signal intensity lesion, but this pattern was also observed for some or all of the lesions in seven of nine patients with gastrinoma metastases. Dynamic FLASH sequences were accurate for lesions larger than 2 cm, hemangiomas displaying a nodular peripheral enhancement with centripetal filling in, and metastases displaying either an initial homogeneous or a regular peripheral enhancement. Precise assessment of lesions smaller than 2 cm remained equivocal. Delayed T1-weighted SE sequence (performed at least 5 min after Gd-chelate injection) was the most accurate technique to identify metastases by showing hypo-or isointensity signal, whereas all hemangiomas were hyperintense. Postcontrast delayed T1-weighted sequence is the primary technique to differentiate equivocal cases of hemangiomas from metastases of gastrinoma. 25 refs., 3 figs., 2 tabs.

Berger, J.F.; Laissy, J.P.; Limot, O.; Cadiot, G. [Hospital Bichat, Paris (France)] [and others] [Hospital Bichat, Paris (France); and others

1996-05-01

100

Gliotoxin potentiates osteoblast differentiation by inhibiting nuclear factor-?B signaling.  

PubMed

The differentiation of pluripotent mesenchymal stem cells to mature osteoblasts is crucial for the maintenance of the adult skeleton. In rheumatic arthritis, osteoblast differentiation is impaired by the overproduction of cytokine tumor necrosis factor (TNF)??. It has been demonstrated that TNF?? is able to inhibit osteoblast differentiation through the activation of nuclear factor (NF)??B signaling. As a result of the critical role of TNF?? and NF??B in the pathogenesis of bone?loss associated diseases, these factors are regarded as key targets for the development of therapeutic agents. In the current study, the role of the NF??B inhibitor gliotoxin (GTX) in the regulation of osteoblast differentiation was evaluated. The non?toxic GTX doses were determined to be ?3 µg/ml. It was revealed that GTX was able to block TNF???induced inhibition of osteoblast differentiation, as indicated by alkaline phosphatase (ALP) activity and ALP staining assays, as well as the expression levels of osteoblast?associated genes Col I, Ocn, Bsp, Runx2, Osx and ATF4. Additionally, it was identified that gliotoxin directly promoted bone morphogenetic protein?2?induced osteoblast differentiation. GTX was found to inhibit the accumulation of NF??B protein p65 in the nucleus and reduce NF??B transcriptional activity, suggesting that GTX potentiated osteoblast differentiation via the suppression of NF-?B signaling. PMID:25816130

Wang, Guangye; Zhang, Xiaohai; Yu, Baoqing; Ren, Ke

2015-07-01

101

Fine-Grain Cell Design for Multiple-Valued Reconfigurable VLSI Using a Single Differential-Pair Circuit  

Microsoft Academic Search

This paper presents a fine-grain cell design for a Multiple-Valued (MV) reconfigurable VLSI using a single Differential-Pair Circuit (DPC). The VLSI involves a bitserial localized data transfer architecture. The cell consists of a Multiple-Valued Source-Coupled Logic (MVSCL)- based threshold logic gate, a dynamic latch and a switch block. The threshold logic gate consists of only one universal comparator. A single

Haque Mohammad Munirul; Michitaka Kameyama

2006-01-01

102

UCP2 regulates energy metabolism and differentiation potential of human pluripotent stem cells  

PubMed Central

It has been assumed, based largely on morphologic evidence, that human pluripotent stem cells (hPSCs) contain underdeveloped, bioenergetically inactive mitochondria. In contrast, differentiated cells harbour a branched mitochondrial network with oxidative phosphorylation as the main energy source. A role for mitochondria in hPSC bioenergetics and in cell differentiation therefore remains uncertain. Here, we show that hPSCs have functional respiratory complexes that are able to consume O2 at maximal capacity. Despite this, ATP generation in hPSCs is mainly by glycolysis and ATP is consumed by the F1F0 ATP synthase to partially maintain hPSC mitochondrial membrane potential and cell viability. Uncoupling protein 2 (UCP2) plays a regulating role in hPSC energy metabolism by preventing mitochondrial glucose oxidation and facilitating glycolysis via a substrate shunting mechanism. With early differentiation, hPSC proliferation slows, energy metabolism decreases, and UCP2 is repressed, resulting in decreased glycolysis and maintained or increased mitochondrial glucose oxidation. Ectopic UCP2 expression perturbs this metabolic transition and impairs hPSC differentiation. Overall, hPSCs contain active mitochondria and require UCP2 repression for full differentiation potential. PMID:22085932

Zhang, Jin; Khvorostov, Ivan; Hong, Jason S; Oktay, Yavuz; Vergnes, Laurent; Nuebel, Esther; Wahjudi, Paulin N; Setoguchi, Kiyoko; Wang, Geng; Do, Anna; Jung, Hea-Jin; McCaffery, J Michael; Kurland, Irwin J; Reue, Karen; Lee, Wai-Nang P; Koehler, Carla M; Teitell, Michael A

2011-01-01

103

Withania somnifera water extract as a potential candidate for differentiation based therapy of human neuroblastomas.  

PubMed

Neuroblastoma is an aggressive childhood disease of the sympathetic nervous system. Treatments are often ineffective and have serious side effects. Conventional therapy of neuroblastoma includes the differentiation agents. Unlike chemo-radiotherapy, differentiation therapy shows minimal side effects on normal cells, because normal non-malignant cells are already differentiated. Keeping in view the limited toxicity of Withania somnifera (Ashwagandha), the current study was aimed to investigate the efficacy of Ashwagandha water extract (ASH-WEX) for anti-proliferative potential in neuroblastoma and its underlying signalling mechanisms. ASH-WEX significantly reduced cell proliferation and induced cell differentiation as indicated by morphological changes and NF200 expression in human IMR-32 neuroblastoma cells. The induction of differentiation was accompanied by HSP70 and mortalin induction as well as pancytoplasmic translocation of the mortalin in ASH-WEX treated cells. Furthermore, the ASH-WEX treatment lead to induction of neural cell adhesion molecule (NCAM) expression and reduction in its polysialylation, thus elucidating its anti-migratory potential, which was also supported by downregulation of MMP 2 and 9 activity. ASH-WEX treatment led to cell cycle arrest at G0/G1 phase and increase in early apoptotic population. Modulation of cell cycle marker Cyclin D1, anti-apoptotic marker bcl-xl and Akt-P provide evidence that ASH-WEX may prove to be a promising phytotherapeutic intervention in neuroblatoma related malignancies. PMID:23383150

Kataria, Hardeep; Wadhwa, Renu; Kaul, Sunil C; Kaur, Gurcharan

2013-01-01

104

The grain production potential assessment with Multiple Cropping Index (MCI) in China  

NASA Astrophysics Data System (ADS)

This paper retrieved the information of cropland and MCI (Multiple Cropping Index) of China in 2000 and 2009 with SPOT NDVI time series data and utilized meteorological data and statistical data released by the state to calculate potential MCI and statistical MCI. Then, the MCI potential of China and grain production potential based on MCI were calculated in order to analyze the potential spatial distribution characteristics of MCI and the potential spatial pattern characteristics. The national mean MCI potentials in 2000 and 2009 are 0.485 and 0.506 respectively calculated with the remote sensing method and statistical method. And the grain productivity potentials of China based on MCI are 51% and 53% respectively. The improvement of MCI potential not only increases hydrothermal utilization rate and the utilization rate of cropland but also enormously enhances the food security degree of China and provides more available cropland area for the economic development.

Gao, Zhiqiang; Ning, Jicai; Gao, Wei

2014-10-01

105

Characterisation and differentiation potential of bone marrow derived canine mesenchymal stem cells.  

PubMed

Mesenchymal stem cells (MSCs) have potential for use in regenerative therapeutics, since they are capable of multi-lineage differentiation. In this study, primary canine MSCs (cMSCs) were isolated from bone marrow aspirates and characterised using marker expression and morphology. cMSCs expressed CD44 and STRO-1, but not CD34 or CD45. Morphologically, cMSCs were similar to previously described MSCs and were capable of chondrocyte differentiation towards articular type cartilage, characterised by increased collagen type II vs. collagen type I expression and expression of Sox-9. cMSCs demonstrated no significant alterations in marker profiles and failed to differentiate into cardiomyocytes in response to a cardiac differentiation protocol or when co-cultured with canine cardiac stem cells. The study indicated that cMSCs can be derived readily from bone marrow and are capable of differentiation into articular cartilage, but appear to have limited ability to differentiate into cardiomyocytes using current protocols. PMID:22721628

Hodgkiss-Geere, Hannah M; Argyle, David J; Corcoran, Brendan M; Whitelaw, Bruce; Milne, Elspeth; Bennett, David; Argyle, Sally A

2012-12-01

106

Differential School Effects among Low, Middle, and High Social Class Composition Schools: A Multiple Group, Multilevel Latent Growth Curve Analysis  

ERIC Educational Resources Information Center

This study uses large-scale survey data and a multiple group, multilevel latent growth curve model to examine differential school effects between low, middle, and high social class composition public schools. The results show that the effects of school inputs and school practices on learning differ across the 3 subpopulations. Moreover, student…

Palardy, Gregory J.

2008-01-01

107

Multiple Bytes Differential Fault Analysis on CLEFIA Xin-jie ZHAO, Tao WANG, Jing-zhe GAO  

E-print Network

Multiple Bytes Differential Fault Analysis on CLEFIA Xin-jie ZHAO, Tao WANG, Jing-zhe GAO of the world have made many security analyses on it. In the previous DFA attacks on CLEFIA, Chen et al.[14 to #12;2 Xin-jie ZHAO, Tao WANG, Jing-zhe GAO recover 4 bytes of the rth round key, after attacking

108

Affect Traits in Differential Diagnosis of Anxiety, Depressive, and Schizophrenic Disorders Using the Multiple Affect Adjective Check List-Revised.  

ERIC Educational Resources Information Center

The effectiveness of the affect trait scales of the revised Multiple Affect Adjective Check List (MAACL-R) (M. Zuckerman and B. Lubin, 1985) in differentiating anxiety, mood, and schizophrenic disorders was studied with 185 psychiatric patients and 185 matched comparisons. Results indicate that the MAACL-R is valid for both global and specific…

Lubin, Bernard; Van Whitlock, Rodney; Zuckerman, Marvin

1998-01-01

109

HMG-CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis  

Microsoft Academic Search

Impaired remyelination due to degener- ation of both postmitotic oligodendrocytes and oligo- dendrocyte progenitors (OPs) is the major hallmark of inflammatory demyelination in multiple sclerosis (MS) lesions and experimental autoimmune encephalomy- elitis (EAE). Here, we have demonstrated the poten- tial of lovastatin, a HMG-CoA reductase inhibitor, for the restoration of impaired remyelination mediated through enhanced survival and differentiation of OPs

Ajaib S. Paintlia; Manjeet K. Paintlia; Mushfiquddin Khan; Timothy Vollmer; Avtar K. Singh; Inderjit Singh

2005-01-01

110

Holographic electrical and thermal conductivity in strongly coupled gauge theory with multiple chemical potentials  

E-print Network

We study transport coefficients of strongly coupled gauge theory in the presence of multiple chemical potential which are dual to rotating D3, M2 and M5 brane. Using the general form of the perturbation equations, we compute DC-electrical conductivity at finite temperature as well as at zero temperature. We also study thermal conductivity for the same class of black holes and show that thermal conductivity and viscosity obeys Wiedemann-Franz like law even in the presence of multiple chemical potential.

Sachin Jain

2010-04-05

111

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis  

PubMed Central

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump inhibitor or antacid to prevent or ameliorate this disturbance. Additionally, patients with multiple sclerosis may be taking these medications independent of corticosteroid treatment. Interventions for gastric disturbances can influence the activation state of the immune system, a principal mediator of pathology in multiple sclerosis. Although histamine release promotes inflammation, activation of the histamine receptor-2 can suppress a proinflammatory immune response, and blocking histamine receptor-2 with an antagonist could shift the balance more towards immune stimulation. Studies utilizing an animal model of multiple sclerosis indicate that histamine receptor-2 antagonists potentially augment disease activity in patients with multiple sclerosis. In contrast, proton pump inhibitors appear to favor immune suppression, but have not been studied in models of multiple sclerosis. Antacids, histamine receptor-2 antagonists and proton pump inhibitors also could alter the intestinal microflora, which may indirectly lead to immune stimulation. Additionally, elevated gastric pH can promote the vitamin B12 deficiency that patients with multiple sclerosis are at risk of developing. Here, we review possible roles of gastric acid inhibitors on immunopathogenic mechanisms associated with multiple sclerosis. PMID:22676575

2012-01-01

112

Differential regulation of interleukin-6 receptors by interleukin-6 and interferons in multiple myeloma cell lines.  

PubMed

Interleukin-6 (IL-6) mediates pleiotropic functions through specific receptors (IL-6R) composed of an 80-kDa binding protein, associated with a non-ligand binding protein (gp130) which transduces the signal. Because IL-6 is the major tumor growth factor in multiple myeloma, we investigated the regulation of IL-6R in two human multiple myeloma cell lines. Binding experiments with 125I-labeled IL-6 showed that IL-6R were expressed at a high density on RPMI-8226 cells (15 000 receptors/cell), but no specific binding was detected on XG-1 cells, whose growth depends on the presence of exogenous IL-6. However, when IL-6 was removed from the culture medium, high-affinity IL-6R appeared on the surface of XG-1 cells (5300 sites/cell). Treatment of RPMI-8226 cells with IL-6 reduced the number of IL-6R without changing their affinity. This reduction was dose dependent and was not affected by acid treatment which dissociates ligand-receptor complexes. Cross-linking experiments showed that the formation of one IL-6/receptor complex of 160 kDa markedly decreased upon IL-6 treatment, while the other complex of 190 kDa became undetectable. These data provide evidence for ligand-induced down-regulation of membrane IL-6R expression in myeloma cells. Treatment of RPMI-8226 cells with interferon-alpha (IFN-alpha), which inhibits the growth of these cells, stimulated IL-6R expression and increased the formation of the 160-kDa IL-6/receptor complex. This stimulation was specific for IFN-alpha, since IFN-gamma reduced the number of IL-6R. These data indicate that, in myeloma cells, IL-6R are differentially regulated by IL-6 and IFN-alpha. PMID:8020547

Lasfar, A; Wietzerbin, J; Billard, C

1994-01-01

113

Investigating osteogenic differentiation in multiple myeloma using a novel 3D bone marrow niche model.  

PubMed

Clonal proliferation of plasma cells within the bone marrow (BM) affects local cells, such as mesenchymal stromal cells (MSCs), leading to osteolysis and fatality in multiple myeloma (MM). Consequently, there is an urgent need to find better mechanisms of inhibiting myeloma growth and osteolytic lesion development. To meet this need and accelerate clinical translation, better models of myeloma within the BM are required. Herein we have developed a clinically relevant, three-dimensional (3D) myeloma BM coculture model that mimics bone cell/cancer cell interactions within the bone microenvironment. The coculture model and clinical samples were used to investigate myeloma growth, osteogenesis inhibition, and myeloma-induced abnormalities in MM-MSCs. This platform demonstrated myeloma support of capillary-like assembly of endothelial cells and cell adhesion-mediated drug resistance (CAM-DR). Also, distinct normal donor (ND)- and MM-MSC miRNA (miR) signatures were identified and used to uncover osteogenic miRs of interest for osteoblast differentiation. More broadly, our 3D platform provides a simple, clinically relevant tool to model cancer growth within the bone-useful for investigating skeletal cancer biology, screening compounds, and exploring osteogenesis. Our identification and efficacy validation of novel bone anabolic miRs in MM opens more opportunities for novel approaches to cancer therapy via stromal miR modulation. PMID:25205118

Reagan, Michaela R; Mishima, Yuji; Glavey, Siobhan V; Zhang, Yong; Manier, Salomon; Lu, Zhi Ning; Memarzadeh, Masoumeh; Zhang, Yu; Sacco, Antonio; Aljawai, Yosra; Shi, Jiantao; Tai, Yu-Tzu; Ready, John E; Kaplan, David L; Roccaro, Aldo M; Ghobrial, Irene M

2014-11-20

114

On orthogonality constrained multiple core-hole states and optimized effective potential method.  

PubMed

An attempt to construct a multiple core-hole state within the optimized effective potential (OEP) methodology is presented. In contrast to the conventional ?-self-consistent field method for hole states, the effects of removing an electron is achieved using some orthogonality constraints imposed on the orbitals so that a Slater determinant describing a hole state is constrained to be orthogonal to that of a neutral system. It is shown that single, double, and multiple core-hole states can be treated within a unified framework and can be easily implemented for atoms and molecules. For this purpose, a constrained OEP method proposed earlier for excited states (Glushkov and Levy, J. Chem. Phys. 2007, 126, 174106) is further developed to calculate single and double core ionization energies using a local effective potential expressed as a direct mapping of the external potential. The corresponding equations, determining core-hole orbitals from a one-particle Schrödinger equation with a local potential as well as correlation corrections derived from the second-order many-body perturbation theory are given. One of the advantages of the present direct mapping formulation is that the effective potential, which plays the role of the Kohn-Sham potential, has the symmetry of the external potential. Single and double core ionization potentials computed with the presented scheme were found to be in agreement with data available from experiment and other calculations. We also discuss core-hole state local potentials for the systems studied. PMID:22696265

Glushkov, V N; Assfeld, X

2012-10-01

115

Determination of Kohn-Sham effective potentials from electron densities using the differential virial theorem.  

PubMed

We present an accurate method for constructing the Kohn-Sham effective potential corresponding to a given electron density in one-dimensional and spherically symmetric systems. The method is based on the differential virial theorem--an exact relation between the effective potential, the electron density, and the kinetic energy density. A distinctive feature of the proposed technique is that it employs a size-consistent bosonic reference potential to ensure the correct asymptotic behavior of the resulting Kohn-Sham potential. We describe a practical implementation of our method and use it to obtain high-quality exchange-correlation and correlation potentials of the neon and argon atoms from ab initio densities generated in large Slater- and Gaussian-type basis sets. PMID:23126701

Ryabinkin, Ilya G; Staroverov, Viktor N

2012-10-28

116

Multiplication  

NSDL National Science Digital Library

How sharp are your multiplication skills? Give these great math games a try ! Play Asteroids blaster and test your multiplication skills. How fast can you solve the problem... play a round of Baseball multiplication and see! Multiplication is fun and delicious with Crazy Cones. Help Lemonade Larry determine the correct amount! Test your multiplication skills with Tic Tac Toe! ...

Ms.Roberts

2009-02-24

117

Fine structure of neurally differentiated iPS cells generated from a multiple sclerosis (MS) patient: a case study.  

PubMed

We compared the characteristics of neural cells derived from induced pluripotent stem (iPS) cells from a patient with multiple sclerosis versus neurally differentiated control iPS cells of a healthy individual. The iPS cells were differentiated toward the oligodendrocyte lineage using a four-step protocol established for the differentiation of embryonic stem cells. The resulting cell population was immunostained on day 112 of differentiation for the presence of oligodendrocytes and analyzed by transmission electron microscopy (TEM). Both patient and control samples resembled a mixed population of neural cells rather than oligodendroglia of high purity, including neural stem cell-like cells and possibly oligodendrocytes demonstrable by TEM. PMID:25335881

Herszfeld, Daniella; Payne, Natalie L; Sylvain, Aude; Sun, Guizhi; Bernard, Claude C; Clark, Joan; Sathananthan, Henry

2014-12-01

118

Yolk Sac Mesenchymal Progenitor Cells from New World Mice (Necromys lasiurus) with Multipotent Differential Potential  

PubMed Central

Fetal membranes are abundant, ethically acceptable and readily accessible sources of stem cells. In particular, the yolk sac is a source of cell lineages that do not express MHCs and are mainly free from immunological incompatibles when transferred to a recipient. Although data are available especially for hematopoietic stem cells in mice and human, whereas other cell types and species are dramatically underrepresented. Here we studied the nature and differentiation potential of yolk sac derived mesenchymal stem cells from a New World mouse, Necromys lasiurus. Explants from mid-gestation were cultured in DMEM-High glucose medium with 10% defined fetal bovine serum. The cells were characterized by standard methods including immunophenotyping by fluorescence and flow cytometry, growth and differentiation potential and tumorigenicity assays. The first adherent cells were observed after 7 days of cell culture and included small, elongated fibroblast-like cells (92.13%) and large, round epithelial-like cells with centrally located nuclei (6.5%). Only the fibroblast-like cells survived the first passages. They were positive to markers for mesenchymal stem cells (Stro-1, CD90, CD105, CD73) and pluripotency (Oct3/4, Nanog) as well as precursors of hematopoietic stem cells (CD117). In differentiation assays, they were classified as a multipotent lineage, because they differentiated into osteogenic, adipogenic, and chondrogenic lineages and, finally, they did not develop tumors. In conclusion, mesenchymal progenitor cells with multipotent differentiation potential and sufficient growth and proliferation abilities were able to be obtained from Necromys yolk sacs, therefore, we inferred that these cells may be promising for a wide range of applications in regenerative medicine. PMID:24918429

Favaron, Phelipe Oliveira; Mess, Andrea; Will, Sônia Elisabete; Maiorka, Paulo César; de Oliveira, Moacir Franco; Miglino, Maria Angelica

2014-01-01

119

Yolk sac mesenchymal progenitor cells from New World mice (Necromys lasiurus) with multipotent differential potential.  

PubMed

Fetal membranes are abundant, ethically acceptable and readily accessible sources of stem cells. In particular, the yolk sac is a source of cell lineages that do not express MHCs and are mainly free from immunological incompatibles when transferred to a recipient. Although data are available especially for hematopoietic stem cells in mice and human, whereas other cell types and species are dramatically underrepresented. Here we studied the nature and differentiation potential of yolk sac derived mesenchymal stem cells from a New World mouse, Necromys lasiurus. Explants from mid-gestation were cultured in DMEM-High glucose medium with 10% defined fetal bovine serum. The cells were characterized by standard methods including immunophenotyping by fluorescence and flow cytometry, growth and differentiation potential and tumorigenicity assays. The first adherent cells were observed after 7 days of cell culture and included small, elongated fibroblast-like cells (92.13%) and large, round epithelial-like cells with centrally located nuclei (6.5%). Only the fibroblast-like cells survived the first passages. They were positive to markers for mesenchymal stem cells (Stro-1, CD90, CD105, CD73) and pluripotency (Oct3/4, Nanog) as well as precursors of hematopoietic stem cells (CD117). In differentiation assays, they were classified as a multipotent lineage, because they differentiated into osteogenic, adipogenic, and chondrogenic lineages and, finally, they did not develop tumors. In conclusion, mesenchymal progenitor cells with multipotent differentiation potential and sufficient growth and proliferation abilities were able to be obtained from Necromys yolk sacs, therefore, we inferred that these cells may be promising for a wide range of applications in regenerative medicine. PMID:24918429

Favaron, Phelipe Oliveira; Mess, Andrea; Will, Sônia Elisabete; Maiorka, Paulo César; de Oliveira, Moacir Franco; Miglino, Maria Angelica

2014-01-01

120

Reduced Differentiation Potential of Primary MyoD?/? Myogenic Cells Derived from Adult Skeletal Muscle  

PubMed Central

To gain insight into the regeneration deficit of MyoD?/? muscle, we investigated the growth and differentiation of cultured MyoD?/? myogenic cells. Primary MyoD?/? myogenic cells exhibited a stellate morphology distinct from the compact morphology of wild-type myoblasts, and expressed c-met, a receptor tyrosine kinase expressed in satellite cells. However, MyoD?/? myogenic cells did not express desmin, an intermediate filament protein typically expressed in cultured myoblasts in vitro and myogenic precursor cells in vivo. Northern analysis indicated that proliferating MyoD?/? myogenic cells expressed fourfold higher levels of Myf-5 and sixfold higher levels of PEA3, an ETS-domain transcription factor expressed in newly activated satellite cells. Under conditions that normally induce differentiation, MyoD?/? cells continued to proliferate and with delayed kinetics yielded reduced numbers of predominantly mononuclear myocytes. Northern analysis revealed delayed induction of myogenin, MRF4, and other differentiation-specific markers although p21 was upregulated normally. Expression of M-cadherin mRNA was severely decreased whereas expression of IGF-1 was markedly increased in MyoD?/? myogenic cells. Mixing of lacZ-labeled MyoD?/? cells and wild-type myoblasts revealed a strict autonomy in differentiation potential. Transfection of a MyoD-expression cassette restored cytomorphology and rescued the differentiation deficit. We interpret these data to suggest that MyoD?/? myogenic cells represent an intermediate stage between a quiescent satellite cell and a myogenic precursor cell. PMID:10037786

Sabourin, Luc A.; Girgis-Gabardo, Adele; Seale, Patrick; Asakura, Atsushi; Rudnicki, Michael A.

1999-01-01

121

The Human Transient Receptor Potential Vanilloid Type 6 Distal Promoter Contains Multiple Vitamin D  

E-print Network

The Human Transient Receptor Potential Vanilloid Type 6 Distal Promoter Contains Multiple Vitamin D lines, we used a chromatin immuno- precipitation (ChIP) scanning method to search for possible vitamin D at 1.2, 2.1, 3.5, 4.3, and 5.5 kb. Despite the ChIP analy- ses, only regions of the TRPV6 gene

Pike, J. Wesley

122

Adipogenic Potential of Multiple Human Adenoviruses In Vivo and In Vitro in Animals  

NSDL National Science Digital Library

Journal Article Â?Adipogenic potential of multiple human adenoviruses in vivo and in vitro in animals,Â? by Leah D. Whigham, Barbara A. Israel, and Richard L. Atkinson, found in the American Journal of Physiology-Regulatory, Integrative and Comparative Physiology.

Leah D. Whigham (University of Wisconsin-Madison Departments of Medicine and Nutritional Sciences)

2006-01-01

123

Appearance potential spectroscopy with a photon counting detector and multiple scattering spectral interpretation.  

PubMed

We describe a soft x-ray appearance potential spectroscopy apparatus, which uses a windowless hyperpure Ge detector operated in the photon counting mode. Direct comparisons of recorded spectra with the self-convolution of x-ray absorption spectra and with ab initio simulations in the multiple scattering framework are reported and discussed. PMID:22938308

Amidani, L; Pasquini, L; Boscherini, F

2012-08-01

124

Exact distorted-wave approach to multiple-scattering theory for general potentials  

E-print Network

We present a new approach to real-space multiple-scattering theory for molecules and clusters, based on the two-potential (distorted-wave) Lippmann-Schwinger equation formalism. Our approach uses a recently developed form [D. L. Foulis, Phys. Rev. A70, 022706 (2004)], for the partial-wave expansions of the exact time-independent single-particle Green function for a general potential, to solve exactly the scattering problem for the distorting potential. The multiple-scattering problem for the full multicenter molecular potential is then developed along familiar lines, within a partition of space consisting of non-overlapping atomic spheres, but relative to the distorting potential. To achieve this some new general Green-function re-expansion formulas are derived, as well as further developments of our earlier partial-wave expansions. Based on the division of the multicenter molecular potential into the non-singular distorting potential and a remaining singular part we develop explicitly the secular equations of our approach and prove a result concerning the symmetry of the atomic matrices. The new secular equations are similar in overall form to those of related methods, requiring coupled radial Schr\\"odinger-equation solutions for each atomic center, together with atomic-sphere surface integrals, but no volume integrals. We treat both continuum (scattering) states and bound states within the same framework, and consider also the case of an outer sphere.

D. L. Foulis

2008-06-03

125

Determination of Helium - Helium Potential Energy Function by Inversion of Differential Cross Sections  

NASA Astrophysics Data System (ADS)

The He - He interaction at short range was studied via a detailed examination of Firsov's inversion theory and the various conditions to which it is subject. Experimental differential cross sections at 0.5 keV and 1.0 keV determined by Abrahams and Peterson were inverted to obtain He(,2) ground state potential energies. It was found that the practical application of Firsov's theory is subject to three conditions. These conditions result from (1) difficulties associated with the absolute measurement of differential cross sections, (2) lack of experimental measurements for scattering at angles less than some minimum angle, and (3) inelastic scattering contributions to the cross section at large scattering angles. A practical procedure for inversion of experimental cross sections was investigated. This procedure explicitly treats the three conditions cited above. It was found that experimental differential cross sections must be corrected for the effect of finite scattering geometry. A procedure for effecting this correction was developed. A semi-theoretical He(,2) potential energy function was determined by slightly adjusting the scale of distance for a potential energy function obtained by inversion such that at 0.529 A the potential energy is 25.0 eV. Electronic energies derived from this potential energy function are within 1.0 eV of ab initio He(,2) electronic energies over the range 0.5 A to 1.0 A and are not in conflict with the variation theorem of quantum mechanics. This result supports the Born-Oppenheimer description of He - He scattering. It was observed that the equations describing both direct and inverse classical scattering consist of integrals which can be reduced to the form. (DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI). A quadrature formula based on expansion of f(x,y) in shifted Chebyshev polynomials has been derived for evaluating this integral.

Lambrakos, Samuel George

126

Fibronectin promotes differentiation of neural crest progenitors endowed with smooth muscle cell potential  

SciTech Connect

The neural crest (NC) is a model system used to investigate multipotency during vertebrate development. Environmental factors control NC cell fate decisions. Despite the well-known influence of extracellular matrix molecules in NC cell migration, the issue of whether they also influence NC cell differentiation has not been addressed at the single cell level. By analyzing mass and clonal cultures of mouse cephalic and quail trunk NC cells, we show for the first time that fibronectin (FN) promotes differentiation into the smooth muscle cell phenotype without affecting differentiation into glia, neurons, and melanocytes. Time course analysis indicated that the FN-induced effect was not related to massive cell death or proliferation of smooth muscle cells. Finally, by comparing clonal cultures of quail trunk NC cells grown on FN and collagen type IV (CLIV), we found that FN strongly increased both NC cell survival and the proportion of unipotent and oligopotent NC progenitors endowed with smooth muscle potential. In contrast, melanocytic progenitors were prominent in clonogenic NC cells grown on CLIV. Taken together, these results show that FN promotes NC cell differentiation along the smooth muscle lineage, and therefore plays an important role in fate decisions of NC progenitor cells.

Costa-Silva, Bruno [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Coelho da Costa, Meline; Melo, Fernanda Rosene; Neves, Cynara Mendes [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Alvarez-Silva, Marcio [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Calloni, Giordano Wosgrau [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Ciencias Morfologicas, Instituto de Ciencias da Saude, Universidade Federal do Rio de Janeiro - Ilha do Fundao, 21949-590, Rio de Janeiro, R.J. (Brazil); Trentin, Andrea Goncalves [Departamento de Biologia Celular, Embriologia e Genetica, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil); Programa de Pos-graduacao em Neurociencias, Centro de Ciencias Biologicas, Universidade Federal de Santa Catarina, Campus Universitario - Trindade, 88040-900, Florianopolis, S.C. (Brazil)], E-mail: atrentin@ccb.ufsc.br

2009-04-01

127

Nuclear Matter Expansion Parameters from the Measurement of Differential Multiplicities for Lambda Production in Central Au+Au Collisions at AGS  

E-print Network

The double differential multiplicities and rapidity distributions for Lambda hyperon production in central Au+Au interactions at AGS in the range of rapidities from 1.7 to 3.2 and the range of transverse kinetic energies from 0.0 to 0.7 GeV are parametrized in terms of the the Blast Wave approximation. The longitudinal and transverse radial expansion parameters and the mean temperature of Lambda hyperons after the freeze-out of the nuclear matter are presented. The predictions of the RQMD model with and without mean field potentials are compared to our data. Both variants of RQMD are parameterized in terms of the Blast Wave model and the results of such parameterizations are compared to the experimental ones. It is found that inclusion of the mean field potentials in RQMD is essential to account for the strong expansion observed in the data.

S. Ahmad; B. E. Bonner; S. V. Efremov; G. S. Mutchler; E. D. Platner; H. W. Themann

1998-03-13

128

Neural differentiation potential of peripheral blood- and bone-marrow-derived precursor cells  

PubMed Central

Transplantation of mesenchymal stem cells (MSCs) prepared from adult bone marrow (BMSCs) has been reported to ameliorate functional deficits in several CNS diseases in experimental animal models. Bone marrow was enriched in MSCs by selecting for plastic-adherent cells that were grown to confluency in appropriate culture conditions as flattened fibroblast-like cells. Despite the fact that the stem/precursor cells in peripheral blood are widely used for reconstruction in the hematopoietic system, it is not fully understood whether peripheral blood-derived plastic-adherent precursor/stem cells (PMSCs) can differentiate into a neural lineage. To compare the potential of PMSCs and BMSCs for neural differentiation in vitro, BMSCs and PMSCs were prepared from the adult rat and expanded in culture. Although the growth rate of PMSCs was less than BMSCs, immunocytochemical and RT-PCR analyses indicated that both MSC types were successfully induced to nestin-positive neurospheres in the presence of EGF and bFGF. After withdrawal of the mitogens, these cells could differentiate into neurofilament-positive neurons or GFAP-positive glia. Thus, our findings suggest the potential use of PMSCs for a cell therapy in CNS diseases. PMID:17064670

Kim, Sangnyon; Honmou, Osamu; Kato, Kazunori; Nonaka, Tadashi; Houkin, Kiyohiro; Hamada, Hirufumi; Kocsis, Jeffery D.

2008-01-01

129

Hot spots of wetland vegetation reduction in relation to human accessibility: differentiating human impacts on natural ecosystems at multiple scales  

Microsoft Academic Search

Human activities have profoundly influenced natural ecosystems, especially wetlands. This study attempted to differentiate\\u000a the impact of human activities on reductions in wetland vegetation in the Lixiahe wetlands, China, at multiple spatial scales.\\u000a The reduction in wetland vegetation from 1988 to 2006 was quantified using Landsat data, and moving window analysis was used\\u000a to detect hot spots of vegetation reduction

Sheng ShengChi; Chi Xu; Shaowei Zhang; Shuqing An; Maosong Liu; Xuejiao Yang

130

Peak inductor current and differential-mode voltage control of single-inductor multiple-output buck converters in CCM  

Microsoft Academic Search

A new control technique, peak inductor current and differential-mode voltage control technique, for non-isolated single-inductor multiple-output (SIMO) buck converters is investigated in this paper. The proposed control method can realize independent control of different output of the SIMO converters operating in continuous conduction mode (CCM) to reduce cross-regulation effect. By taking a three outputs converter as an example, simulation is

Songrong Wu; Wei Wang; Jianping Xu; Guohua Zhou; Xiaojuan Wei

2009-01-01

131

Differentiation  

NSDL National Science Digital Library

This is an activity about lunar magmatic differentiation, in which learners simulate the process of geological differentiation. The activity ends with an extension question that asks about the makeup of the highlands of the Moon. This activity is in Unit 2 of the Exploring the Moon teacher's guide and is designed for use especially, but not exclusively, with the Lunar Sample Disk program.

2012-08-03

132

Human eosinophils constitutively express multiple Th1, Th2, and immunoregulatory cytokines that are secreted rapidly and differentially  

PubMed Central

Eosinophils are innate immune leukocytes implicated in the initiation and maintenance of type 2 immune responses, including asthma and allergy. The ability to store and rapidly secrete preformed cytokines distinguishes eosinophils from most lymphocytes, which must synthesize cytokine proteins prior to secretion and may be a factor in the apparent Th2 bias of eosinophils. Multiple studies confirm that human eosinophils from atopic or hypereosinophilic donors can secrete over 30 cytokines with a varying and often opposing immune-polarizing potential. However, it remains unclear whether all of these cytokines are constitutively preformed and available for rapid secretion from eosinophils in the circulation of healthy individuals or are restricted to eosinophils from atopic donors. Likewise, the relative concentrations of cytokines stored within eosinophils have not been studied. Here, we demonstrate that human blood eosinophils are not singularly outfitted with Th2-associated cytokines but rather, constitutively store a cache of cytokines with nominal Th1, Th2, and regulatory capacities, including IL-4, IL-13, IL-6, IL-10, IL-12, IFN-?, and TNF-?. We demonstrate further rapid and differential release of each cytokine in response to specific stimuli. As agonists, strong Th1 and inflammatory cytokines elicited release of Th2-promoting IL-4 but not Th1-inducing IL-12. Moreover, a large quantity of IFN-? was secreted in response to Th1, Th2, and inflammatory stimuli. Delineations of the multifarious nature of preformed eosinophil cytokines and the varied stimulus-dependent profiles of rapid cytokine secretion provide insights into the functions of human eosinophils in mediating inflammation and initiation of specific immunity. PMID:18840671

Spencer, Lisa A.; Szela, Craig T.; Perez, Sandra A. C.; Kirchhoffer, Casey L.; Neves, Josiane S.; Radke, Amy L.; Weller, Peter F.

2009-01-01

133

Paeoniflorin, a natural neuroprotective agent, modulates multiple anti-apoptotic and pro-apoptotic pathways in differentiated PC12 cells.  

PubMed

Numerous studies have shown robust neuroprotective effects of paeoniflorin (PF), a natural compound derived from the herbal medicine Paeony radix. In the present study, we determined associations of PF neuroprotection with its modulation of various apoptotic and anti-apoptotic pathways. PF (50-400 ?M) pretreatment significantly improved viability of differentiated PC12 cells exposed to methyl-4-phenylpyridine ion (MPP(+)), a neurotoxin, and inhibited over-release of lactate dehydrogenase, a biomarker of neuronal cell death. PF also ameliorated MPP(+)-induced nuclear and mitochondrial apoptotic alteration and intracellular calcium overload. PF treatment reversed MPP(+) suppression of activity of B cell lymphoma-extra large, which is a mitochondrial membrane molecule that protects cells from DNA damage-induced apoptosis, and strikingly inhibited the enhanced level of cleaved poly(ADP-ribose)polymerase, which is involved in the process of apoptosis. PF alone and coadministration with MPP(+) enhanced phospho activation of extracellular signal-regulated kinases, Akt, and its downstream element glycogen synthase kinase-3, but the effects were completely abolished in the presence of their blockers PD98059 and LY294002. The presence of the blockers also diminished the potency of PF in improving viability of MPP(+)-exposed cells. These results indicate that neuroprotective effects of PF are related to its modulation of multiple anti-apoptotic and pro-apoptotic pathways, including blockade of intracellular calcium overload, prevention of mitochondrial membrane integrity, inhibition of pro-apoptotic molecules, and up-regulation of anti-apoptotic proteins associated with cell survival and proliferation. The study provides evidence supporting PF as a potential therapeutic agent used for the treatment of neurodegenerative diseases and neural injury. PMID:23436209

Wang, Di; Wong, Hei Kiu; Feng, Yi-Bin; Zhang, Zhang-Jin

2013-05-01

134

Proliferation and differentiation potential of human adipose-derived mesenchymal stem cells isolated from elderly patients with osteoporotic fractures  

PubMed Central

Abstract Aging has less effect on adipose-derived mesenchymal stem cells (ADSCs) than on bone marrow-derived mesenchymal stem cells (BMSCs), but whether the fact holds true in stem cells from elderly patients with osteoporotic fractures is unknown. In this study, ADSCs and BMSCs of the same donor were harvested and divided into two age groups. Group A consisted of 14 young patients (36.4 ± 11.8 years old), and group B consisted of eight elderly patients (71.4 ± 3.6 years old) with osteoporotic fractures. We found that the doubling time of ADSCs from both age groups was maintained below 70 hrs, while that of BMSCs increased significantly with the number of passage. When ADSCs and BMSCs from the same patient were compared, there was a significant increase in the doubling time of BMSCs in each individual from passages 3 to 6. On osteogenic induction, the level of matrix mineralization of ADSCs from group B was comparable to that of ADSCs from group A, whereas BMSCs from group B produced least amount of mineral deposits and had a lower expression level of osteogenic genes. The p21 gene expression and senescence-associated ?-galactosidase activity were lower in ADSCs compared to BMSCs, which may be partly responsible for the greater proliferation and differentiation potential of ADSCs. It is concluded that the proliferation and osteogenic differentiation of ADSCs were less affected by age and multiple passage than BMSCs, suggesting that ADSCs may become a potentially effective therapeutic option for cell-based therapy, especially in elderly patients with osteoporosis. PMID:21545685

Chen, Hui-Ting; Lee, Mon-Juan; Chen, Chung-Hwan; Chuang, Shu-Chun; Chang, Li-Fu; Ho, Mei-Ling; Hung, Shao-Hung; Fu, Yin-Chih; Wang, Yan-Hsiung; Wang, Hsin-I; Wang, Gwo-Jaw; Kang, Lin; Chang, Je-Ken

2012-01-01

135

Glioblastoma-dependent differentiation and angiogenic potential of human mesenchymal stem cells in vitro.  

PubMed

Tumor angiogenesis is of central importance in the malignancy of glioblastoma multiforme (GBM). As previously shown, human mesenchymal stem cells (hMSC) migrate towards GBM and are incorporated into tumor microvessels. However, phenotype and function of recruited hMSC remain unclear. We evaluated the differentiation and angiogenic potential of hMSC after stimulation with glioblastoma-conditioned medium in vitro. Immunostaining with endothelial, smooth muscle cell and pericyte markers was used to analyze hMSC differentiation in different concentrations of tumor-conditioned medium (CM), and the angiogenic potential was evaluated by matrigel-based tube-formation assay (TFA). Immunofluorescence staining revealed that tumor-conditioned hMSC (CM-hMSC) expressed CD 151, VE-cadherin, desmin, ?-smooth muscle actin, nestin, and nerval/glial antigen 2 (NG2) in a CM concentration-dependent manner, whereas no expression of von-Willebrand factor (vWF) and smooth myosin could be detected. These findings are indicative of GBM-dependent differentiation of hMSC into pericyte-like cells, rather than endothelial or smooth muscle cells. Furthermore, TFA of hMSC and CM-hMSC revealed CM-dependent formation of capillary-like networks, which differed substantially from those formed by human endothelial cells (HUVEC), also implying pericyte-like tube formation. These results are indicative of GBM-derived differentiation of hMSC into pericyte-like mural cells, which might contribute to the neovascularization and stabilization of tumor vessels. PMID:21547397

Birnbaum, Tobias; Hildebrandt, Jenna; Nuebling, Georg; Sostak, Petra; Straube, Andreas

2011-10-01

136

Explant-derived human dental pulp stem cells enhance differentiation and proliferation potentials  

PubMed Central

Abstract Numerous stem cell niches are present in the different tissues and organs of the adult human body. Among these tissues, dental pulp, entrapped within the ‘sealed niche’ of the pulp chamber, is an extremely rich site for collecting stem cells. In this study, we demonstrate that the isolation of human dental pulp stem cells by the explants culture method (hD-DPSCs) allows the recovery of a population of dental mesenchymal stem cells that exhibit an elevated proliferation potential. Moreover, we highlight that hD-DPSCs are not only capable of differentiating into osteoblasts and chondrocytes but are also able to switch their genetic programme when co-cultured with murine myoblasts. High levels of MyoD expression were detected, indicating that muscle-specific genes in dental pulp cells can be turned on through myogenic fusion, confirming thus their multipotency. A perivascular niche may be the potential source of hD-DPSCs, as suggested by the consistent Ca2+ release from these cells in response to endothelin-1 (ET-1) treatment, which is also able to significantly increase cell proliferation. Moreover, response to ET-1 has been found to be superior in hD-DPSCs than in DPSCs, probably due to the isolation method that promotes release of stem/progenitor cells from perivascular structures. The ability to isolate, expand and direct the differentiation of hD-DPSCs into several lineages, mainly towards myogenesis, offers an opportunity for the study of events associated with cell commitment and differentiation. Therefore, hD-DPSCs display enhanced differentiation abilities when compared to DPSCs, and this might be of relevance for their use in therapy. PMID:19602052

Spath, L; Rotilio, V; Alessandrini, M; Gambara, G; De Angelis, L; Mancini, M; Mitsiadis, T A; Vivarelli, E; Naro, F; Filippini, A; Papaccio, G

2010-01-01

137

IL-12 Directs Further Maturation of Ex Vivo Differentiated NK Cells with Improved Therapeutic Potential  

PubMed Central

The possibility to modulate ex vivo human NK cell differentiation towards specific phenotypes will contribute to a better understanding of NK cell differentiation and facilitate tailored production of NK cells for immunotherapy. In this study, we show that addition of a specific low dose of IL-12 to an ex vivo NK cell differentiation system from cord blood CD34+ stem cells will result in significantly increased proportions of cells with expression of CD62L as well as KIRs and CD16 which are preferentially expressed on mature CD56dim peripheral blood NK cells. In addition, the cells displayed decreased expression of receptors such as CCR6 and CXCR3, which are typically expressed to a lower extent by CD56dim than CD56bright peripheral blood NK cells. The increased number of CD62L and KIR positive cells prevailed in a population of CD33+NKG2A+ NK cells, supporting that maturation occurs via this subtype. Among a series of transcription factors tested we found Gata3 and TOX to be significantly downregulated, whereas ID3 was upregulated in the IL-12-modulated ex vivo NK cells, implicating these factors in the observed changes. Importantly, the cells differentiated in the presence of IL-12 showed enhanced cytokine production and cytolytic activity against MHC class I negative and positive targets. Moreover, in line with the enhanced CD16 expression, these cells exhibited improved antibody-dependent cellular cytotoxicity for B-cell leukemia target cells in the presence of the clinically applied antibody rituximab. Altogether, these data provide evidence that IL-12 directs human ex vivo NK cell differentiation towards more mature NK cells with improved properties for potential cancer therapies. PMID:24498025

Sturtzel, Caterina; Tordoir, Marleen; Schlechta, Bernhard; Groenewegen, Dirk; Hofer, Erhard

2014-01-01

138

IL-12 directs further maturation of ex vivo differentiated NK cells with improved therapeutic potential.  

PubMed

The possibility to modulate ex vivo human NK cell differentiation towards specific phenotypes will contribute to a better understanding of NK cell differentiation and facilitate tailored production of NK cells for immunotherapy. In this study, we show that addition of a specific low dose of IL-12 to an ex vivo NK cell differentiation system from cord blood CD34(+) stem cells will result in significantly increased proportions of cells with expression of CD62L as well as KIRs and CD16 which are preferentially expressed on mature CD56(dim) peripheral blood NK cells. In addition, the cells displayed decreased expression of receptors such as CCR6 and CXCR3, which are typically expressed to a lower extent by CD56(dim) than CD56(bright) peripheral blood NK cells. The increased number of CD62L and KIR positive cells prevailed in a population of CD33(+)NKG2A(+) NK cells, supporting that maturation occurs via this subtype. Among a series of transcription factors tested we found Gata3 and TOX to be significantly downregulated, whereas ID3 was upregulated in the IL-12-modulated ex vivo NK cells, implicating these factors in the observed changes. Importantly, the cells differentiated in the presence of IL-12 showed enhanced cytokine production and cytolytic activity against MHC class I negative and positive targets. Moreover, in line with the enhanced CD16 expression, these cells exhibited improved antibody-dependent cellular cytotoxicity for B-cell leukemia target cells in the presence of the clinically applied antibody rituximab. Altogether, these data provide evidence that IL-12 directs human ex vivo NK cell differentiation towards more mature NK cells with improved properties for potential cancer therapies. PMID:24498025

Lehmann, Dorit; Spanholtz, Jan; Sturtzel, Caterina; Tordoir, Marleen; Schlechta, Bernhard; Groenewegen, Dirk; Hofer, Erhard

2014-01-01

139

Therapeutic potential of motor neurons differentiated from embryonic stem cells and induced pluripotent stem cells.  

PubMed

Degeneration of motor neurons (MN) caused by disease or injury leads to paralysis and is fatal in some conditions. To date, there are no effective treatments for MN disorders; therefore, cell therapy is a promising strategy to replace lost MN. Embryonic stem (ES) cells isolated from the inner cell mass of mammalian blastocysts self-renew and are pluripotent because they differentiate into cell types of the three germinal layers. Reprogramming of adult cells to a state similar to ES cells, termed induced pluripotent stem (iPS) cells, has been recently reported. It is well established that pluripotent cell types can give rise to specialized phenotypes, including neurons. Mouse, monkey and human MN can be differentiated from ES and iPS cells using procedures generally involving embryoid bodies formation and stimulation with retinoic acid and Sonic hedgehog. Differentiated MN express characteristic molecular markers such as Islet1, HB9 and Choline acetyltransferase, exhibit electrophysiological maturity and are able to form synaptic contacts similar to neuromuscular junctions in vitro. Furthermore, transplanted MN promote functional recovery in animal models of neurodegenerative diseases and MN injury. The potential clinical applications of stem cell-derived MN was enhanced after iPS cell derivation, which makes possible the generation of patient-specific pluripotent cells for autologous cell replacement therapies and may be used for drug development and disease modeling. This review summarizes MN differentiation protocols from ES and iPS cells in regard to neuronal differentiation efficiency, expression of MN markers and functional properties in vitro, as well as their therapeutic effects after grafting. PMID:22293229

López-González, Rodrigo; Velasco, Iván

2012-01-01

140

A Monte Carlo method for chemical potential determination in single and multiple occupancy crystals  

E-print Network

We describe a Monte Carlo scheme which, in a single simulation, yields a measurement of the chemical potential of a crystalline solid. Within the isobaric ensemble, this immediately provides an estimate of the system free energy, with statistical uncertainties that are determined precisely and transparently. An extension to multiple occupancy ("cluster") solids permits the direct determination of the cluster chemical potential and hence the equilibrium conditions. We apply the method to a model exhibiting cluster crystalline phases, where we find evidence for an infinite cascade of critical points terminating coexistence between crystals of differing site occupancies.

Nigel B. Wilding; Peter Sollich

2012-09-14

141

Multiplication  

NSDL National Science Digital Library

Here are some fun games to make practicing multiplication fun!!! Before you start the fun... click Multiplication Tables to review what you already know! Can you figure out the Multiplication Hidden Picture... you better know your math skills first or the picture will burst! It\\'s times to have a \\"blast\\"... Blow me away with theMultiplication Tunnel Blaster Now your ready to join the team! Show me ...

Ms. Walker

2008-03-26

142

Determination of spent nuclear fuel assembly multiplication with the differential die-away self-interrogation instrument  

NASA Astrophysics Data System (ADS)

We present a novel method for determining the multiplication of a spent nuclear fuel assembly with a Differential Die-Away Self-Interrogation (DDSI) instrument. The signal, which is primarily created by thermal neutrons, is measured with four 3He detector banks surrounding a spent fuel assembly. The Rossi-alpha distribution (RAD) at early times reflects coincident events from single fissions as well as fission chains. Because of this fact, the early time domain contains information about both the fissile material and spontaneous fission material in the assembly being measured. A single exponential function fit to the early time domain of the RAD has a die-away time proportional to the spent fuel assembly (SFA) multiplication. This correlation was tested by simulating assay of 44 different SFAs with the DDSI instrument. The SFA multiplication was determined with a variance of 0.7%.

Kaplan, Alexis C.; Henzl, Vladimir; Menlove, Howard O.; Swinhoe, Martyn T.; Belian, Anthony P.; Flaska, Marek; Pozzi, Sara A.

2014-09-01

143

Comparison of the profiles of the potential teachers in different disciplines based on multiple intelligences theory (Samsun City Sample)  

Microsoft Academic Search

In this study, the profiles based on multiple intelligences theory of a total of 908 potential teachers studying in Science, Social Sciences, Mathematics, Music, Art and Physical Education at Ondokuz May?s University are compared. Multiple intelligences inventory which was taken from Saban has been used to determine the intelligence areas of the potential teachers. The collected data has been evaluated

Hasan Sözen; Merve Sözen; Atilla Tekat

2009-01-01

144

Development of resting membrane potentials in differentiating murine neuroblastoma cells (N1E-115) evaluated by flow cytometry  

Microsoft Academic Search

With the aid of a voltage-sensitive oxonol dye, flow cytometry was used to measure relative changes in resting membrane potential\\u000a (Vm) and forward angle light scatter (FALS) profiles of a differentiating\\/differentiated murine neuroblastoma cell line (N1E-115).\\u000a Electrophysiological differentiation was characterized by Vm establishment. The (Vm)-time profile was found to be seed cell concentration-dependent for cell densities of less than 2

William S. Kisaalita; John M. Bowen

1997-01-01

145

Articular cartilage-derived cells hold a strong osteogenic differentiation potential in comparison to mesenchymal stem cells in vitro  

SciTech Connect

Cartilaginous matrix-degenerative diseases like osteoarthritis (OA) are characterized by gradual cartilage erosion, and also by increased presence of cells with mesenchymal stem cell (MSC) character within the affected tissues. Moreover, primary chondrocytes long since are known to de-differentiate in vitro and to be chondrogenically re-differentiable. Since both findings appear to conflict with each other, we quantitatively assessed the mesenchymal differentiation potential of OA patient cartilage-derived cells (CDC) towards the osteogenic and adipogenic lineage in vitro and compared it to that of MSC isolated from adipose tissue (adMSC) of healthy donors. We analyzed expression of MSC markers CD29, CD44, CD105, and CD166, and, following osteogenic and adipogenic induction in vitro, quantified their expression of osteogenic and adipogenic differentiation markers. Furthermore, CDC phenotype and proliferation were monitored. We found that CDC exhibit an MSC CD marker expression pattern similar to adMSC and a similar increase in proliferation rate during osteogenic differentiation. In contrast, the marked reduction of proliferation observed during adipogenic differentiation of adMSC was absent in CDC. Quantification of differentiation markers revealed a strong osteogenic differentiation potential for CDC, however almost no capacity for adipogenic differentiation. Since in the pathogenesis of OA, cartilage degeneration coincides with high bone turnover rates, the high osteogenic differentiation potential of OA patient-derived CDC may affect clinical therapeutic regimens aiming at autologous cartilage regeneration in these patients. - Highlights: • We analyze the mesenchymal differentiation capacity of cartilage-derived cells (CDC). • CDC express mesenchymal stem cell (MSC) markers CD29, CD44, CD105, and CD166. • CDC and MSC proliferation is reduced in adipogenesis and increased in osteogenesis. • Adipogenic differentiation is virtually absent in CDC, but strong in MSC. • Osteogenic differentiation is significantly stronger for CDC than for MSC.

Salamon, Achim, E-mail: achim.salamon@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Jonitz-Heincke, Anika, E-mail: anika.jonitz@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Adam, Stefanie, E-mail: stefanie.adam@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Rychly, Joachim, E-mail: joachim.rychly@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany); Müller-Hilke, Brigitte, E-mail: brigitte.mueller-hilke@med.uni-rostock.de [Institute of Immunology, Rostock University Medical Center, Schillingallee 68, D-18057 Rostock (Germany); Bader, Rainer, E-mail: rainer.bader@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Lochner, Katrin, E-mail: katrin.lochner@med.uni-rostock.de [Biomechanics and Implant Technology Research Laboratory, Department of Orthopedics, Rostock University Medical Center, Doberaner Straße 142, D-18057 Rostock (Germany); Peters, Kirsten, E-mail: kirsten.peters@med.uni-rostock.de [Department of Cell Biology, Rostock University Medical Center, Schillingallee 69, D-18057 Rostock (Germany)

2013-11-01

146

A shift from adaptive to innate immunity: a potential mechanism of disease progression in multiple sclerosis.  

PubMed

Multiple sclerosis is postulated to be a T cell-mediated autoimmune disease characterised by a relapsing-remitting stage followed by a secondary progressive phase. The relapsing remitting phase may involve waves of proinflammatory Th1 and Th17 cells that infiltrate the nervous system, provoking a clinical attack. The activity of these cells is modulated by other populations of regulatory T cells and the balance between the pro-inflammatory and regulatory T cells is critical for determining disease activity. Promoting the activity of regulatory cells is a potentially beneficial therapeutic strategy, and probably contributes to the action of glatiramer acetate. The progressive phase of multiple sclerosis is believed to be secondary to neurodegenerative changes triggered by inflammation. The status of the innate immune system and its relationship to the stages of multiple sclerosis has been poorly defined until recently. However, recent data suggest that these results demonstrate abnormalities of dendritic cell activation or maturation may underlie the transition to the progressive phase of the disease. Preventing this transition, perhaps by acting at the level of the innate immune system, is an important treatment goal. The identification of biomarkers to predict disease course and treatment response is a major challenge in multiple sclerosis research. Studies using antigen arrays have identified antibody patterns related to CNS antigens and heat-shock proteins that are associated with different disease stages and with response to therapy. In the future, such antibody repertoires could be used as biomarkers for the diagnosis and evaluation of patients with multiple sclerosis, for matching treatments to individual patients and, potentially, to identify healthy individuals at risk for this autoimmune disease. PMID:18317671

Weiner, Howard L

2008-03-01

147

Proliferation and differentiation potential of human adipose-derived stem cells grown on chitosan hydrogel.  

PubMed

Applied tissue engineering in regenerative medicine warrants our enhanced understanding of the biomaterials and its function. The aim of this study was to evaluate the proliferation and differentiation potential of human adipose-derived stem cells (hADSCs) grown on chitosan hydrogel. The stability of this hydrogel is pH-dependent and its swelling property is pivotal in providing a favorable matrix for cell growth. The study utilized an economical method of cross linking the chitosan with 0.5% glutaraldehyde. Following the isolation of hADSCs from omentum tissue, these cells were cultured and characterized on chitosan hydrogel. Subsequent assays that were performed included JC-1 staining for the mitochondrial integrity as a surrogate marker for viability, cell proliferation and growth kinetics by MTT assay, lineage specific differentiation under two-dimensional culture conditions. Confocal imaging, scanning electron microscopy (SEM), and flow cytometry were used to evaluate these assays. The study revealed that chitosan hydrogel promotes cell proliferation coupled with > 90% cell viability. Cytotoxicity assays demonstrated safety profile. Furthermore, glutaraldehyde cross linked chitosan showed < 5% cytotoxicity, thus serving as a scaffold and facilitating the expansion and differentiation of hADSCs across endoderm, ectoderm and mesoderm lineages. Additional functionalities can be added to this hydrogel, particularly those that regulate stem cell fate. PMID:25746846

Debnath, Tanya; Ghosh, Sutapa; Potlapuvu, Usha Shalini; Kona, Lakshmi; Kamaraju, Suguna Ratnakar; Sarkar, Suprabhat; Gaddam, Sumanlatha; Chelluri, Lakshmi Kiran

2015-01-01

148

Proliferation and Differentiation Potential of Human Adipose-Derived Stem Cells Grown on Chitosan Hydrogel  

PubMed Central

Applied tissue engineering in regenerative medicine warrants our enhanced understanding of the biomaterials and its function. The aim of this study was to evaluate the proliferation and differentiation potential of human adipose-derived stem cells (hADSCs) grown on chitosan hydrogel. The stability of this hydrogel is pH-dependent and its swelling property is pivotal in providing a favorable matrix for cell growth. The study utilized an economical method of cross linking the chitosan with 0.5% glutaraldehyde. Following the isolation of hADSCs from omentum tissue, these cells were cultured and characterized on chitosan hydrogel. Subsequent assays that were performed included JC-1 staining for the mitochondrial integrity as a surrogate marker for viability, cell proliferation and growth kinetics by MTT assay, lineage specific differentiation under two-dimensional culture conditions. Confocal imaging, scanning electron microscopy (SEM), and flow cytometry were used to evaluate these assays. The study revealed that chitosan hydrogel promotes cell proliferation coupled with > 90% cell viability. Cytotoxicity assays demonstrated safety profile. Furthermore, glutaraldehyde cross linked chitosan showed < 5% cytotoxicity, thus serving as a scaffold and facilitating the expansion and differentiation of hADSCs across endoderm, ectoderm and mesoderm lineages. Additional functionalities can be added to this hydrogel, particularly those that regulate stem cell fate. PMID:25746846

Debnath, Tanya; Ghosh, Sutapa; Potlapuvu, Usha Shalini; Kona, Lakshmi; Kamaraju, Suguna Ratnakar; Sarkar, Suprabhat; Gaddam, Sumanlatha; Chelluri, Lakshmi Kiran

2015-01-01

149

Methodology for Estimating Solar Potential on Multiple Building Rooftops for Photovoltaic Systems  

SciTech Connect

In this paper, a methodology for estimating solar potential on multiple building rooftops is presented. The objective of this methodology is to estimate the daily or monthly solar radiation potential on individual buildings in a city/region using Light Detection and Ranging (LiDAR) data and a geographic information system (GIS) approach. Conceptually, the methodology is based on the upward-looking hemispherical viewshed algorithm, but applied using an area-based modeling approach. The methodology considers input parameters, such as surface orientation, shadowing effect, elevation, and atmospheric conditions, that influence solar intensity on the earth s surface. The methodology has been implemented for some 212,000 buildings in Knox County, Tennessee, USA. Based on the results obtained, the methodology seems to be adequate for estimating solar radiation on multiple building rooftops. The use of LiDAR data improves the radiation potential estimates in terms of the model predictive error and the spatial pattern of the model outputs. This methodology could help cities/regions interested in sustainable projects to quickly identify buildings with higher potentials for roof-mounted photovoltaic systems.

Kodysh, Jeffrey B [ORNL; Omitaomu, Olufemi A [ORNL; Bhaduri, Budhendra L [ORNL; Neish, Bradley S [ORNL

2013-01-01

150

Identification of a Proximal Progenitor Population from Murine Fetal Lungs with Clonogenic and Multilineage Differentiation Potential  

PubMed Central

Summary Lung development-associated diseases are major causes of morbidity and lethality in preterm infants and children. Access to the lung progenitor/stem cell populations controlling pulmonary development during embryogenesis and early postnatal years is essential to understand the molecular basis of such diseases. Using a Nkx2-1mCherry reporter mouse, we have identified and captured Nkx2-1-expressing lung progenitor cells from the proximal lung epithelium during fetal development. These cells formed clonal spheres in semisolid culture that could be maintained in vitro and demonstrated self-renewal and expansion capabilities over multiple passages. In-vitro-derived Nkx2-1-expressing clonal spheres differentiated into a polarized epithelium comprised of multiple cell lineages, including basal and secretory cells, that could repopulate decellularized lung scaffolds. Nkx2-1 expression thus defines a fetal lung epithelial progenitor cell population that can be used as a model system to study pulmonary development and associated pediatric diseases. PMID:25358791

Bilodeau, Mélanie; Shojaie, Sharareh; Ackerley, Cameron; Post, Martin; Rossant, Janet

2014-01-01

151

Keratin 6 Expression Correlates to Areas of Squamous Differentiation in Multiple Independent Isolates of As+3-Induced Bladder Cancer  

PubMed Central

This laboratory has shown that arsenite (As+3) exposure can cause the malignant transformation of the UROtsa human urothelial cell line. This single isolate formed subcutaneous tumors with a histology similar to human urothelial cell carcinoma. The tumors also displayed areas of squamous differentiation of the urothelial cells, an infrequent, but known component of human bladder cancer. In the present study, five additional independent isolates of As+3 -transformed urothelial cells were isolated and each were shown to produce subcutaneous urothelial cell tumors with a characteristic histology very similar to those described in the initial report. That there were underlying phenotypic differences in the 6 independent isolates was demonstrated when they were assessed for their ability to form tumors within the peritoneal cavity. It was shown that two isolates could form hundreds of small peritoneal tumor nodules, one isolate a moderate number of tumor nodules, and three isolates no or only one tumor nodule. The peritoneal tumors were also characterized for their degree of squamous differentiation of the urothelial cells and, while areas of squamous differentiation could be found, such differentiation was substantially reduced compared to subcutaneous tumors. Immunostaining for keratin 6 was tested as a potential marker for malignant urothelial cells that had undergone squamous differentiation. Keratin 6 was shown to consistently stain only cells having some evidence of squamous differentiation. Keratin 16 was shown to follow the staining pattern of keratin 6. The isolates and tumor heterotransplants were all examined for keratin 6, 16 and 17 mRNA and protein expression. PMID:20186695

Cao, Ling; Zhou, Xu Dong; Sens, Mary Ann; Garrett, Scott H.; Zheng, Yun; Dunlevy, Jane R.; Sens, Donald A.; Somji, Seema

2011-01-01

152

Inductance Compensation of Multiple Capacitors With Application to Common- and Differential-Mode Filters  

E-print Network

Capacitor parasitic inductance often limits the high-frequency performance of electromagnetic interference (EMI) filters in both common-mode (CM) and differential-mode (DM) filtering domains. However, these limitations can ...

Pierquet, Brandon J.

153

Smart SUDS: recognising the multiple-benefit potential of sustainable surface water management systems.  

PubMed

How can we make sustainable urban drainage systems (SUDS) smart? SUDS help us to manage surface water runoff from urban environments but they are capable of delivering much more. This paper looks beyond the water quantity and quality improvement functions of SUDS and investigates the multiple benefits that can be gained by implementing smart SUDS solutions. This work provides a new perspective, using methodologies not normally associated with SUDS research, to determine multiple benefits. The outputs of the work can potentially assist decision-makers, designer and planners in recognising the potential for multiple benefits that can be delivered by SUDS. The ecosystem services (ES) associated with a large redevelopment in Dundee, Scotland, UK, are identified and a public perception study together with public participatory geographical information system (PPGIS) methods was used to confirm the goods and benefits of the SUDS. The paper presents findings on the public perception of SUDS as they provide cultural benefits such as recreation, aesthetics and biodiversity. The results show that greenspace is important when choosing a location, and willingness to pay for greenspace is high in this area. This paper concludes that SUDS provide multi-functional benefits in relation to the ES, thereby justifying the cachet of being termed Smart SUDS. PMID:25633948

Jose, Roshni; Wade, Rebecca; Jefferies, Chris

2015-01-01

154

Numerical solution of potential flow about arbitrary 2-dimensional multiple bodies  

NASA Technical Reports Server (NTRS)

A procedure for the finite-difference numerical solution of the lifting potential flow about any number of arbitrarily shaped bodies is given. The solution is based on a technique of automatic numerical generation of a curvilinear coordinate system having coordinate lines coincident with the contours of all bodies in the field, regardless of their shapes and number. The effects of all numerical parameters involved are analyzed and appropriate values are recommended. Comparisons with analytic solutions for single Karman-Trefftz airfoils and a circular cylinder pair show excellent agreement. The technique of application of the boundary-fitted coordinate systems to the numerical solution of partial differential equations is illustrated.

Thompson, J. F.; Thames, F. C.

1982-01-01

155

Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function.  

PubMed

In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer (PCa). However, the mechanisms of prostate-specific regulation and functional evolution of TRPM8 during PCa progression remain unclear. Here we show, for the first time to our knowledge, that only secretory mature differentiated human prostate primary epithelial (PrPE) luminal cells expressed functional plasma membrane TRPM8 ((PM)TRPM8) channels. Moreover, PCa epithelial cells obtained from in situ PCa were characterized by a significantly stronger (PM)TRPM8-mediated current than that in normal cells. This (PM)TRPM8 activity was abolished in dedifferentiated PrPE cells that had lost their luminal secretory phenotype. However, we found that in contrast to (PM)TRPM8, endoplasmic reticulum TRPM8 ((ER)TRPM8) retained its function as an ER Ca(2+) release channel, independent of cell differentiation. We hypothesize that the constitutive activity of (ER)TRPM8 may result from the expression of a truncated TRPM8 splice variant. Our study provides insight into the role of TRPM8 in PCa progression and suggests that TRPM8 is a potentially attractive target for therapeutic intervention: specific inhibition of either (ER)TRPM8 or (PM)TRPM8 may be useful, depending on the stage and androgen sensitivity of the targeted PCa. PMID:17510704

Bidaux, Gabriel; Flourakis, Matthieu; Thebault, Stéphanie; Zholos, Alexander; Beck, Benjamin; Gkika, Dimitra; Roudbaraki, Morad; Bonnal, Jean-Louis; Mauroy, Brigitte; Shuba, Yaroslav; Skryma, Roman; Prevarskaya, Natalia

2007-06-01

156

Prostate cell differentiation status determines transient receptor potential melastatin member 8 channel subcellular localization and function  

PubMed Central

In recent years, the transient receptor potential melastatin member 8 (TRPM8) channel has emerged as a promising prognostic marker and putative therapeutic target in prostate cancer (PCa). However, the mechanisms of prostate-specific regulation and functional evolution of TRPM8 during PCa progression remain unclear. Here we show, for the first time to our knowledge, that only secretory mature differentiated human prostate primary epithelial (PrPE) luminal cells expressed functional plasma membrane TRPM8 (PMTRPM8) channels. Moreover, PCa epithelial cells obtained from in situ PCa were characterized by a significantly stronger PMTRPM8-mediated current than that in normal cells. This PMTRPM8 activity was abolished in dedifferentiated PrPE cells that had lost their luminal secretory phenotype. However, we found that in contrast to PMTRPM8, endoplasmic reticulum TRPM8 (ERTRPM8) retained its function as an ER Ca2+ release channel, independent of cell differentiation. We hypothesize that the constitutive activity of ERTRPM8 may result from the expression of a truncated TRPM8 splice variant. Our study provides insight into the role of TRPM8 in PCa progression and suggests that TRPM8 is a potentially attractive target for therapeutic intervention: specific inhibition of either ERTRPM8 or PMTRPM8 may be useful, depending on the stage and androgen sensitivity of the targeted PCa. PMID:17510704

Bidaux, Gabriel; Flourakis, Matthieu; Thebault, Stéphanie; Zholos, Alexander; Beck, Benjamin; Gkika, Dimitra; Roudbaraki, Morad; Bonnal, Jean-Louis; Mauroy, Brigitte; Shuba, Yaroslav; Skryma, Roman; Prevarskaya, Natalia

2007-01-01

157

Differential expression profiling of microRNAs and their potential involvement in esophageal squamous cell carcinoma.  

PubMed

MicroRNAs are small, noncoding RNAs approximately 18-24 nucleotides in length that negatively regulate gene expression at the posttranscriptional and/or translational level by binding to complimentary sequences in the 3'-untranslated regions of target mRNAs. Growing evidence has indicated the important roles for different miRNA species in the development of different cancers. Therefore, miRNAs have the potential to become new biological markers for esophageal squamous cell carcinoma (ESCC) and to be applied in the diagnosis, prognosis, and targeted treatment of ESCC. In this study, we performed a miRNA microarray to analyze the miRNA expression profile in ESCC compared to normal tissues. Then, we made a preliminary analysis of the biological function for the most differentially expressed miRNAs and their potentially target genes regulated. Some microarray results were validated by performing quantitative RT-PCR. The study provided evidence that linked the biological role of miRNAs to ESCC and showed that miRNAs could undertake a variety of mechanisms. Additionally, we also found that altered miR-429 and miR-451 expression levels were associated with the occurrence of lymph node metastases and the differentiation status and TNM stage in ESCC. The study of miRNAs may lead to finding novel methods to diagnose, treat, and prevent ESCC. PMID:24272087

Zang, Wenqiao; Wang, Yuanyuan; Du, Yuwen; Xuan, Xiaoyan; Wang, Tao; Li, Min; Ma, Yunyun; Li, Ping; Chen, Xudong; Dong, Ziming; Zhao, Guoqiang

2014-04-01

158

Selected Extracellular microRNA as Potential Biomarkers of Multiple Sclerosis Activity-Preliminary Study.  

PubMed

Multiple sclerosis (MS) is an autoimmune demyelinating disease of the central nervous system (CNS). Four distinct disease courses are known, although approximately 90 % of patients are diagnosed with the relapsing-remitting form (RRMS). The name "multiple sclerosis" pertains to the underlying pathology: the presence of demyelinating plaques in the CNS, in particular in the periventricular region, corpus callosum, cervical spine, and the cerebellum. There are ongoing efforts to discover biomarkers that would allow for an unequivocal diagnosis, assess the activity of inflammatory and neurodegenerative processes, or warn of disease progression. At present, small noncoding RNA particles-microRNA (miRNA, miR) seem to be particularly noteworthy, as they take part in posttranscriptional regulation of expression of various genes. Changes in composition as well as function of miRNA found in body fluids of MS patients are subjects of research, in the hope they prove accurate markers of MS activity. This preliminary study aims to evaluate the expression of selected extracellular microRNA particles (miRNA-let-7a, miRNA-92a, miRNA-684a) in patients experiencing MS relapse and remission, with healthy volunteers serving as a control group and to evaluate the correlation between miRNA expression and selected clinical parameters of those patients. Thirty-seven patients suffering from MS formed two examined groups: 20 patients undergoing relapse and 17 in remission. Thirty healthy volunteers formed the control group. All patients who were subjects to peripheral blood sampling had been hospitalized in the Department of Neurology and Stroke(1). Four milliliters of venous whole blood had been collected into EDTA tubes. The basis for the selection of the three particular miRNA investigated in this study (miRNA-let-7a, miRNA-92a, miRNA-684a) was a preliminary bioinformatic analysis of data compiled from several medical databases, including Ovid MEDLINE®, Embase, Cochrane Database of Systematic Reviews (CDSR), miRWalk, and miRBase. The isolation of extracellular microRNA from plasma was carried out using miRNeasy Mini Kit (Qiagen) reagents. The reverse transcription was carried out with TaqMan® MicroRNA Reverse Transcription Kit (Applied Biosystems), as per manufacturers' instructions. Standard microRNA TaqMan® tests (Applied Biosystems) were used for miRNA quantification. The qPCR were performed on a 7900 HT Fast Real-Time PCR System (Applied Biosystems) and analyzed using Sequence Detection System 2.3 software. In addition, all patients at the Department of Neurology and Stroke undergo a routine complete blood count with differential. The main objective of this study was to evaluate the expression of selected microRNA (has-miR-let-7a, miR-92a, and miR-648a) in the plasma of patients with MS during a relapse as well as in remission and attempt to correlate the acquired data with clinically relevant parameters of the disease. Finding such correlations may potentially lead to the use of miRNA as a biomarker of MS, which could help diagnose the disease and assess its severity and the efficacy of treatment. The difference in the expression of has-miR-let-7a in the remission group and the control group was statistically significant (p?=?0.002). Similarly, the expression of miRNA-648a in patients in remission was significantly different from the expression in the control group (p?=?0.02). Analysis of the correlation between the expression of miRNA-92a and the severity of the disease as measured by the EDSS scale in patients undergoing relapse showed significant negative linear correlation (r?=?-0.54, p?=?0.01). Higher miR-648a expression correlated with more frequent flare-ups in the joint group of patients in remission and relapse (p?=?0.03). This study is one of the few that demonstrate significantly changed expression of selected extracellular miRNA in plasma of MS patients and correlate those findings with clinical parameters. These observations may suggest that some miRNA subsets may be potential biomarkers for

Kacperska, Magdalena Justyna; Jastrzebski, Karol; Tomasik, Bartlomiej; Walenczak, Jakub; Konarska-Krol, Maria; Glabinski, Andrzej

2015-05-01

159

Differentiation  

NSDL National Science Digital Library

In the five parts of this video, we define the derivative and then build a cribsheet of rules for expressing the slopes of simple functions and combinations of functions. These include the power rule, the chain rule, the product and quotient rules, and the rules for differentiating sinusoidal functions.

2013-06-21

160

Differentiation  

NSDL National Science Digital Library

The derivative refers to the rate of change, or slope, of a function. Differentiation refers to the calculation of a derivative. Derivatives are used throughout applied mathematics and science. The derivative of a function is the instantaneous rate of change of a function evaluated at each point.

David Joiner

161

Platelet Rich Concentrate Promotes Early Cellular Proliferation and Multiple Lineage Differentiation of Human Mesenchymal Stromal Cells In Vitro  

PubMed Central

Platelet rich concentrate (PRC) is a natural adjuvant that aids in human mesenchymal stromal cell (hMSC) proliferation in vitro; however, its role requires further exploration. This study was conducted to determine the optimal concentration of PRC required for achieving the maximal proliferation, and the need for activating the platelets to achieve this effect, and if PRC could independently induce early differentiation of hMSC. The gene expression of markers for osteocytes (ALP, RUNX2), chondrocytes (SOX9, COL2A1), and adipocytes (PPAR-?) was determined at each time point in hMSC treated with 15% activated and nonactivated PRC since maximal proliferative effect was achieved at this concentration. The isolated PRC had approximately fourfold higher platelet count than whole blood. There was no significant difference in hMSC proliferation between the activated and nonactivated PRC. Only RUNX2 and SOX9 genes were upregulated throughout the 8 days. However, protein expression study showed formation of oil globules from day 4, significant increase in ALP at days 6 and 8 (P ? 0.05), and increased glycosaminoglycan levels at all time points (P < 0.05), suggesting the early differentiation of hMSC into osteogenic and adipogenic lineages. This study demonstrates that the use of PRC increased hMSC proliferation and induced early differentiation of hMSC into multiple mesenchymal lineages, without preactivation or addition of differentiation medium. PMID:25436230

Shani, Samuel; Vasudevaraj Naveen, Sangeetha; Murali, Malliga Raman; Puvanan, Karunanithi; Abbas, Azlina Amir; Kamarul, Tunku

2014-01-01

162

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression  

PubMed Central

Background In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage restriction boundaries. Such reports have been based on the detection of neural-related proteins by the differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in populations of non-differentiated MSCs obtained from 4 donors. Results The expression analysis revealed that several of the commonly used marker genes from other studies like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample revealed a unique expression pattern, demonstrating a significant variation of marker expression. Conclusion The present study highlights the existence of an inter-donor variability of expression of neural-related markers in human MSC samples that has not previously been described. This donor-related heterogeneity might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be inappropriate for transplantation strategies. PMID:19257891

Montzka, Katrin; Lassonczyk, Nina; Tschöke, Beate; Neuss, Sabine; Führmann, Tobias; Franzen, Rachelle; Smeets, Ralf; Brook, Gary A; Wöltje, Michael

2009-01-01

163

All-optical differential detection for suppressing multiple-access interference in coherent time-addressed optical CDMA systems.  

PubMed

A novel scheme for suppressing the multiple-access interference (MAI) in coherent time-addressed optical CDMA systems is proposed. This is based on a differential detection using the dual-control NOLM. The basic principle for MAI suppression is described. For experimental demonstration, two encoded channels are constructed and decoded. These decoded signals are sent to the dual-control NOLM and a high autocorrelation peak with suppressed MAI at the output of NOLM is observed. Signal-to-interference ratio is improved by 7 dB. PMID:19475015

Kim, Sun-Jong; Kim, Tae-Young; Park, Chul; Park, Chang-Soo; Chun, Young

2004-05-01

164

Multiple-input NOR logic design using negative differential resistance circuits implemented by standard SiGe process  

NASA Astrophysics Data System (ADS)

A multiple-input NOR logic gate using the negative differential resistance (NDR) circuit is demonstrated. The NDR circuit is composed of four resistors (R) and two SiGe-based heterojunction bipolar transistor (HBT), and it can show the NDR characteristics in the combined current-voltage curve by suitably designing the resistance. Compared to the resonant tunneling diode, the R-HBT-NDR circuit is much easier to be applied to some circuits which are combined with other Si-based or SiGe-based devices and circuits on the same chip. The fabrication is based on the standard 0.35 ?m SiGe BiCMOS process.

Gan, Kwang-Jow; Tsai, Cher-Shiung; Liang, Dong-Shong; Tu, Chun-Da; Chen, Yaw-Hwang

2008-02-01

165

Novel Multiple-Valued Logic Design Using BiCMOS-Based Negative Differential Resistance Circuit Biased by Two Current Sources  

NASA Astrophysics Data System (ADS)

The paper demonstrates a novel multiple-valued logic (MVL) design using a three-peak negative differential resistance (NDR) circuit, which is made of several Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and SiGe-based heterojunction bipolar transistor (HBT) devices. Specifically, this three-peak NDR circuit is biased by two switch-controlled current sources. Compared to the traditional MVL circuit made of resonant tunneling diode (RTD), this multiple-peak MOS-HBT-NDR circuit has two major advantages. One is that the fabrication of this circuit can be fully implemented by the standard BiCMOS process without the need for molecular-beam epitaxy system. Another is that we can obtain more logic states than the RTD-based MVL design. In measuring, we can obtain eight logic states at the output according to a sequent control of two current sources on and off in order.

Gan, Kwang-Jow; Liang, Dong-Shong; Chen, Yan-Wun

166

Isorotation and differential rotation in a magnetic mirror with imposed E Multiplication-Sign B rotation  

SciTech Connect

Doppler spectroscopy of helium impurities in the Maryland Centrifugal Experiment reveals the simultaneous existence of isorotating and differentially rotating magnetic surfaces. Differential rotation occurs at the innermost surfaces and is conjectured to cause plasma voltage oscillations of hundreds of kilohertz by periodically changing the current path inductance. High-speed images show the periodic expulsion of plasma near the mirror ends at the same frequencies. In spite of this, the critical ionization velocity limit is exceeded, with respect to the vacuum field definition, for at least 0.5 ms.

Romero-Talamas, C. A.; Elton, R. C.; Young, W. C.; Reid, R.; Ellis, R. F. [Institute for Research in Electronics and Applied Physics, University of Maryland, College Park, Maryland 20742 (United States)

2012-07-15

167

Evolutionary analysis of the MIXTA gene family highlights potential targets for the study of cellular differentiation.  

PubMed

Differentiated epidermal cells such as trichomes and conical cells perform numerous essential functions in plant biology and are important for our understanding of developmental patterning and cell shape regulation. Many are also commercially significant, such as cotton fibers and trichomes that secrete pharmaceutically useful or herbivore-deterring compounds. Here, we focus on the phylogeny and evolution of the subgroup 9 R2R3 MYB gene transcription factors, which include the MIXTA gene, and that are important for the specification and regulation of plant cellular differentiation. We have sequenced 49 subgroup 9 R2R3 MYB genes from key experimental taxa and combined these sequences with those identified by an exhaustive bioinformatic search, to compile a data set of 223 subgroup 9 R2R3 MYB genes. Our phylogenetic analyses demonstrate, for the first time, the complex evolutionary history of the subgroup 9 R2R3 MYB genes. A duplication event is inferred before the origin of seed plants giving rise to two major gene lineages, here termed SBG9-A and SBG9-B. The evolutionary conservation of the SBG9-B gene lineage has not been previously recognized and its role in cellular differentiation is unknown, thus an entire clade of potential candidate genes for epidermal cell regulation remains to be explored. Using a heterologous transformation bioassay, we provide functional data that implicate members of the SBG9-B lineage in the specification of epidermal projections. Furthermore, we reveal numerous putative duplication events in both SBG9-A and SBG9-B lineages, resolving uncertainty about orthology and paralogy among the subgroup 9 R2R3 MYB genes. Finally, we provide a robust framework over which to interpret existing functional data and to direct ongoing comparative genetic research into the evolution of plant cellular diversity. PMID:23188591

Brockington, Samuel F; Alvarez-Fernandez, Ruben; Landis, Jacob B; Alcorn, Katrina; Walker, Rachel H; Thomas, Murphy M; Hileman, Lena C; Glover, Beverley J

2013-03-01

168

[Multiple functions-targeted algorithms and potential applications of forest simulation optimization system (FSOS)].  

PubMed

Forest Simulation and Optimization System (FSOS) model has been widely used in British Columbia of Canada and in Changbai Mountains of China. This model is based on the viewpoint of harmonized and balanced management of forest resources and the application of simulated annealing optimized algorithms in arranging forest management schemes, aimed to realize the sustainable and harmonized development of forest resources multiple objective management and to transform forests to their desired status. The multiple functions (or the multiple objectives) in the FSOS model include water storage and purification, carbon sequestration, wildlife habitat protection, biodiversity conservation, visual landscape quality, and timber production, and the desired forest status is comprehensively defined by experts, environmental organizations, and government policies. This paper introduced in detail the simulated annealing algorithms in FSOS, including solution representation, evaluations, and transitions, and the potential applications of the algorithms in forest ecosystem planning, aimed to provide helps to the planning and management of forest resources and to the governments to quantify, analyze, and manage the forest resources, effectively monitor forest operations, and achieve the sustainable development of forest ecosystem. PMID:22303689

Liu, Li; Liu, Guo-Liang; Chen, Shao-Zhi; Tian, Chu-Ping

2011-11-01

169

Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications.  

PubMed Central

Carcinoma of the thyroid gland, the most frequently diagnosed endocrine malignancy, is often associated with early regional metastases. With the exception of papillary carcinoma, distinguishing benign from malignant thyroid neoplasms in the absence of metastatic disease is difficult. Recently, the vertebrate lectins galectin-1 and galectin-3 have been implicated in the regulation of cellular growth, differentiation, and malignant transformation of a variety of tissues. To determine whether these galectins have a role in thyroid neoplasia, we analyzed 32 specimens from thyroid malignancies (16 papillary, 7 follicular, 8 medullary carcinomas, and 1 metastasis to lymph node), 10 benign thyroid adenomas, 1 nodular goiter, and 33 specimens from adjacent normal thyroid tissue for the expression of galectin-1 and galectin-3 with immunohistochemical and immunoblotting techniques utilizing anti-galectin antibodies. All thyroid malignancies of epithelial origin (ie, papillary and follicular carcinomas) and a metastatic lymph node from a papillary carcinoma expressed high levels of both galectin-1 and galectin-3. The medullary thyroid carcinomas, which are of parafollicular C cell origin, showed a weaker and variable expression of these galectins. In contrast, neither benign thyroid adenomas nor adjacent normal thyroid tissue expressed galectin-1 or galectin-3. These results suggest that galectin-1 and galectin-3 may be associated with malignant transformation of thyroid epithelium and may potentially serve as markers for distinguishing benign thyroid adenomas from differentiated thyroid carcinomas. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:7677193

Xu, X. C.; el-Naggar, A. K.; Lotan, R.

1995-01-01

170

The concentration-estimation problem for multiple-wavelength differential absorption lidar  

SciTech Connect

We are seeking to develop a reliable methodology for multi-chemicai detection and discrimination based upon multi-wavelength differential absorption lidar measurements. In this paper, we summarize some preliminary results of our efforts to devise suitable concentration-estimation algorithms for use in detection and discrimination schemes.

Payne, A.N.

1994-07-01

171

A Generalized Logistic Regression Procedure to Detect Differential Item Functioning among Multiple Groups  

ERIC Educational Resources Information Center

We present an extension of the logistic regression procedure to identify dichotomous differential item functioning (DIF) in the presence of more than two groups of respondents. Starting from the usual framework of a single focal group, we propose a general approach to estimate the item response functions in each group and to test for the presence…

Magis, David; Raiche, Gilles; Beland, Sebastien; Gerard, Paul

2011-01-01

172

Using Multiple-Variable Matching to Identify Cultural Sources of Differential Item Functioning  

ERIC Educational Resources Information Center

Identifying the sources of differential item functioning (DIF) in international assessments is very challenging, because such sources are often nebulous and intertwined. Even though researchers frequently focus on test translation and content area, few actually go beyond these factors to investigate other cultural sources of DIF. This article…

Wu, Amery D.; Ercikan, Kadriye

2006-01-01

173

Commentary: Differentiated Measures of Temperament and Multiple Pathways to Childhood Disorders  

ERIC Educational Resources Information Center

Provided is a commentary on articles written for a special section on temperament and childhood disorders. Temperament's contributions to the development of childhood disorders are considered both generally and specifically. Questions are raised about the use of terminology in the field, particularly the term difficult. Differentiation of outcomes…

Rothbart, Mary K.

2004-01-01

174

Activities for Differentiated Instruction Addressing All Levels of Bloom's Taxonomy and Eight Multiple Intelligences.  

ERIC Educational Resources Information Center

This manuscript contains 13 curriculum units designed to enhance differentiated instruction for learners with special needs from grades 1-12, including gifted students. It integrates Benjamin S. Bloom's levels of cognitive understanding with Howard Gardner's eight domains of intelligence to provide a framework for individualized instruction. Each…

Rule, Audrey C., Ed.; Lord, Linda Hurley, Ed.

175

Calcium currents of olfactory bulb juxtaglomerular cells: profile and multiple conductance plateau potential simulation.  

PubMed

The olfactory glomerulus is the locus of information transfer between olfactory sensory neurons and output neurons of the olfactory bulb. Juxtaglomerular cells (JGCs) may influence intraglomerular processing by firing plateau potentials that support multiple spikes. It is unclear what inward currents mediate this firing pattern. In previous work, we characterized potassium currents of JGCs. We focus here on the inward currents using whole cell current clamp and voltage recording in a rat in vitro slice preparation, as well as computer simulation. We first showed that sodium current was not required to mediate plateau potentials. Voltage clamp characterization of calcium current (I(Ca)) determined that I(Ca) consisted of a slow activating, rapidly inactivating (?(10%-90% rise) 6-8 ms, ?(inactivation) 38-77 ms) component I(cat1), similar to T-type currents, and a sustained (?(inactivation)>500 ms) component I(cat2), likely composed of L-type and P/Q-type currents. We used computer simulation to test their roles in plateau potential firing. We robustly modeled I(cat1) and I(cat2) to Hodgkin-Huxley schemes (m(3)h and m(2), respectively) and simulated a JGC plateau potential with six conductances: calcium currents as above, potassium currents from our prior study (A-type I(kt1), D-type I(kt2), delayed rectifier I(kt3)), and a fast sodium current (I(Na)). We demonstrated that I(cat1) was required for mediating the plateau potential, unlike I(Na) and I(cat2), and its ?(inactivation) determined plateau duration. We also found that I(kt1) dictated plateau potential shape more than I(kt2) and I(kt3). The influence of these two transient and opposing conductances suggests a unique mechanism of plateau potential physiology. PMID:21704681

Masurkar, A V; Chen, W R

2011-09-29

176

Precision Differential Photometry from a Non-Precision Site (Expanding Undergraduate Research Potential)  

NASA Astrophysics Data System (ADS)

More than a decade ago the first exo-planet transit light curve was observed with modest instruments. This inspired the idea that it might be possible to develop observational and data reduction techniques using our venerable, but ancient 16” Boller & Chivens telescope to achieve the milli-magnitude precision differential photometry necessary for such a project. Such capability with a small instrument in the very “non-photometric” environment of our region (SE USA) greatly expands the potential observational projects available to undergraduate (and faculty) researchers. A brief description of the techniques developed to achieve this capability at the University of North Georgia will be presented. The state of our telescope is such that if these techniques work for us, they should be more than applicable to other researchers at institutions in similar regions with similar sized but more modern instruments.

Jones, Joseph H.

2013-06-01

177

Electrospun scaffolds for multiple tissues regeneration in vivo through topography dependent induction of lineage specific differentiation.  

PubMed

Physical topographic cues from various substrata have been shown to exert profound effects on the growth and differentiation of stem cells due to their niche-mimicking features. However, the biological function of different topographic materials utilized as bio-scaffolds in vivo have not been rigorously characterized. This study investigated the divergent differentiation pathways of mesenchymal stem cells (MSCs) and neo-tissue formation trigged by aligned and randomly-oriented fibrous scaffolds, both in vitro and in vivo. The aligned group was observed to form more mature tendon-like tissue in the Achilles tendon injury model, as evidenced by histological scoring and collagen I immunohistochemical staining data. In contrast, the randomly-oriented group exhibited much chondrogenesis and subsequent bone tissue formation through ossification. Additionally, X-ray imaging and osteocalcin immunohistochemical staining also demonstrated that osteogenesis in vivo is driven by randomly oriented topography. Furthermore, MSCs on the aligned substrate exhibited tenocyte-like morphology and enhanced tenogenic differentiation compared to cells grown on randomly-oriented scaffold. qRT-PCR analysis of osteogenic marker genes and alkaline phosphatase (ALP) staining demonstrated that MSCs cultured on randomly-oriented fiber scaffolds displayed enhanced osteogenic differentiation compared with cells cultured on aligned fiber scaffolds. Finally, it was demonstrated that cytoskeletal tension release abrogated the divergent differentiation pathways on different substrate topography. Collectively, these findings illustrate the relationship between topographic cues of the scaffold and their inductive role in tissue regeneration; thus providing an insight into future development of smart functionalized bio-scaffold design and its application in tissue engineering. PMID:25617136

Yin, Zi; Chen, Xiao; Song, Hai-Xin; Hu, Jia-Jie; Tang, Qiao-Mei; Zhu, Ting; Shen, Wei-Liang; Chen, Jia-Lin; Liu, Huanhuan; Heng, Boon Chin; Ouyang, Hong-Wei

2015-03-01

178

Multiplication  

NSDL National Science Digital Library

Which way of learning multiplication helped you the best? First you will need to use organizer Then you need to go to thinking blocks Next go to multiplication rap song Then go to dinosaur game and times table and lattice method and finally flashcards after this look over your graphic organizer and think about which site was most helpful for you. You will then be divided into groups where you will make your own creative lesson ...

Ms. Williams

2011-04-06

179

REM sleep behaviour disorder differentiates pure autonomic failure from multiple system atrophy with autonomic failure  

PubMed Central

Ten patients with primary autonomic failure, followed up in a prospective clinical and laboratory study, were finally diagnosed as pure autonomic failure or multiple system atrophy with autonomic failure. Polysomnographic studies were performed in all patients. Whereas all four patients with multiple system atrophy complained of sleep related episodes suggesting REM sleep behaviour disorder (RBD) confirmed by polysomnography, RBD remained absent in the remaining six patients with pure autonomic failure. The data indicate that RBD is an important clinical feature, often heralding multiple system atrophy, but which is absent throughout the course of pure autonomic failure; its recognition can thus be useful in the prognostic evaluation of early primary autonomic failure syndromes.?? PMID:9598693

Plazzi, G.; Cortelli, P.; Montagna, P.; De Monte, A.; Corsini, R.; Contin, M.; Provini, F.; Pierangeli, G.; Lugaresi, E.

1998-01-01

180

Evaluation of the biomethane potential from multiple waste streams for a proposed community scale anaerobic digester.  

PubMed

This paper examines the biomethane potential from organic waste for a proposed community scale anaerobic digester in a rural town. The biomethane potential test is used to assess the suitability of waste streams for biomethane production and to examine the variation in biomethane potential between waste sub-streams. A methodology for accurately estimating the biomethane potential from multiple heterogeneous organic waste substrates is sought. Five main waste streams were identified as possible substrates for biogas production, namely Abattoir waste (consisting of paunch and de-watered activated sludge); cheese factory effluent; commercial and domestic food waste; pig slurry and waste water treatment sludge. The biomethane potential of these waste streams ranged from as low as 99 L CH4 kg VS(-1) for pig slurry to as high as 787 L CH4 kg VS(-1) for dissolved air floatation (DAF) sludge from a cheese effluent treatment plant. The kinetic behaviour of the biomethane production in the batch test is also examined. The objective of the paper is to suggest an optimum substrate mix in terms of biomethane yield per unit substrate for the proposed anaerobic digester. This should maximize the yield of biomethane per capital investment. Food waste displayed the highest biomethane yield (128 m(n)(3) t(-1)) followed by cheese waste (38 m(n)(3) t(-1)) and abattoir waste (36 m(n)(3) t(-1)). It was suggested that waste water sludge (16 m(n)(3) t(-1)) and pig slurry (4 m(n)(3) t(-1)) should not be digested. However, the biomethane potential test does not give information on the continuous operation of an anaerobic digester. PMID:24350456

Browne, James D; Allen, Eoin; Murphy, Jerry D

2013-01-01

181

Neurological manifestations of gastrointestinal disorders, with particular reference to the differential diagnosis of multiple sclerosis  

Microsoft Academic Search

. Neurological manifestations of gastrointestinal disorders are described, with particular reference to those resembling multiple sclerosis (MS) on clinical or MRI grounds. Patients with celiac disease can present cerebellar ataxia, progressive myoclonic ataxia, myelopathy, or cerebral, brainstem and peripheral nerve involvement. Antigliadin antibodies can be found in subjects with neurological dysfunction of unknown cause, particularly in sporadic cerebellar ataxia (\\

A. Ghezzi; M. Zaffaroni

2001-01-01

182

Modeling Differential Item Functioning Using a Generalization of the Multiple-Group Bifactor Model  

ERIC Educational Resources Information Center

The authors present a generalization of the multiple-group bifactor model that extends the classical bifactor model for categorical outcomes by relaxing the typical assumption of independence of the specific dimensions. In addition to the means and variances of all dimensions, the correlations among the specific dimensions are allowed to differ…

Jeon, Minjeong; Rijmen, Frank; Rabe-Hesketh, Sophia

2013-01-01

183

Gender and Perceived Illness Severity: Differential Indicators of Employment Concerns for Adults with Multiple Sclerosis?  

ERIC Educational Resources Information Center

Although research has indicated a link between gender and perceived illness severity and the employment status of people with multiple sclerosis (MS), it has not addressed questions regarding the relationship between those variables and specific types of employment concerns. In this study, a sample of 1,310 adults with MS replied to a mail survey…

Roessler, Richard T.; Turner, Ronna C.; Robertson, Judith L.; Rumrill,Phillip D.

2005-01-01

184

Ultrafast differential transmission spectroscopy of excitonic transitions in InGaNGaN multiple quantum wells  

E-print Network

materials using the InGaN system have led to the commercialization of blue, green, and amber light Received 6 June 2002; accepted 15 January 2003 Room-temperature carrier dynamics in InGaN/GaN multiple and excitonic bleaching is consistent with the theoretical value of the piezoelectric field in the strained InGaN

Cartwright, Alexander N.

185

Depletion of histone demethylase KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of stem cells from apical papilla  

SciTech Connect

Mesenchymal stem cells (MSCs) are a reliable resource for tissue regeneration, but the molecular mechanism underlying directed differentiation remains unclear; this has restricted potential MSC applications. The histone demethylase, lysine (K)-specific demethylase 2A (KDM2A), is evolutionarily conserved and ubiquitously expressed members of the JmjC-domain-containing histone demethylase family. A previous study determined that KDM2A can regulate the cell proliferation and osteo/dentinogenic differentiation of MSCs. It is not known whether KDM2A is involved in the other cell lineages differentiation of MSCs. Here, we show that depletion of KDM2A by short hairpin RNAs can enhance adipogenic and chondrogenic differentiation potentials in human stem cells from apical papilla (SCAPs). We found that the stemness-related genes, SOX2, and the embryonic stem cell master transcription factor, NANOG were significantly increased after silence of KDM2A in SCAPs. Moreover, we found that knock-down of the KDM2A co-factor, BCOR also up-regulated the mRNA levels of SOX2 and NANOG. Furthermore, Chromatin immunoprecipitation assays demonstrate that silence of KDM2A increased the histone H3 Lysine 4 (H3K4) trimethylation in the SOX2 and NANOG locus and regulates its expression. In conclusion, our results suggested that depletion of KDM2A enhanced the adipogenic and chondrogenic differentiation potentials of SCAPs by up-regulated SOX2 and NANOG, BCOR also involved in this regulation as co-factor, and provided useful information to understand the molecular mechanism underlying directed differentiation in MSCs. - Highlights: • Depletion of KDM2A enhances adipogenic/chondrogenic differentiation in SCAPs. • Depletion of KDM2A enhances the differentiation of SCAPs by activate SOX2 and NANOG. • Silence of KDM2A increases histone H3 Lysine 4 trimethylation in SOX2 and NANOG. • BCOR is co-factor of KDM2A involved in the differentiation regulation.

Dong, Rui [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Yao, Rui [Department of Pediatrics, Stomatological Hospital of Nankai University, Tianjin 300041 (China); Du, Juan [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Wang, Songlin [Molecular Laboratory for Gene Therapy and Tooth Regeneration, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China); Department of Biochemistry and Molecular Biology, Capital Medical University School of Basic Medical Sciences, Beijing 100069 (China); Fan, Zhipeng, E-mail: zpfan@ccmu.edu.cn [Laboratory of Molecular Signaling and Stem Cells Therapy, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, Capital Medical University School of Stomatology, Beijing 100050 (China)

2013-11-01

186

Identification of circulating microRNAs for the differential diagnosis of Parkinson's disease and Multiple System Atrophy  

PubMed Central

Background: Parkinson's disease (PD) is a progressive neurodegenerative disorder which may be misdiagnosed with atypical conditions such as Multiple System Atrophy (MSA), due to overlapping clinical features. MicroRNAs (miRNAs) are small non-coding RNAs with a key role in post-transcriptional gene regulation. We hypothesized that identification of a distinct set of circulating miRNAs (cmiRNAs) could distinguish patients affected by PD from MSA and healthy individuals. Results. Using TaqMan Low Density Array technology, we analyzed 754 miRNAs and found 9 cmiRNAs differentially expressed in PD and MSA patients compared to healthy controls. We also validated a set of 4 differentially expressed cmiRNAs in PD and MSA patients vs. controls. More specifically, miR-339-5p was downregulated, whereas miR-223*, miR-324-3p, and mir-24 were upregulated in both diseases. We found cmiRNAs specifically deregulated in PD (downregulation of miR-30c and miR-148b) and in MSA (upregulation of miR-148b). Finally, comparing MSA and PD, we identified 3 upregulated cmiRNAs in MSA serum (miR-24, miR-34b, miR-148b). Conclusions. Our results suggest that cmiRNA signatures discriminate PD from MSA patients and healthy controls and may be considered specific, non-invasive biomarkers for differential diagnosis. PMID:24959119

Vallelunga, Annamaria; Ragusa, Marco; Di Mauro, Stefania; Iannitti, Tommaso; Pilleri, Manuela; Biundo, Roberta; Weis, Luca; Di Pietro, Cinzia; De Iuliis, Angela; Nicoletti, Alessandra; Zappia, Mario; Purrello, Michele; Antonini, Angelo

2014-01-01

187

Dkk-1 and IL-7 in plasma of patients with multiple myeloma prevent differentiation of mesenchymal stem cells into osteoblasts  

PubMed Central

Bone disease is the leading cause of morbidity associated with multiple myeloma (MM). Lytic bone lesions have been detected in 90% of patients diagnosed with MM and present a great therapeutic challenge. After the removal of the tumor burden, the bone lesions persist and the bone remodeling homeostasis is not restored even in patients in clinical remission. To determine whether systemic factors generated by malignant MM cells can skew the osteoblast (OB) differentiation program of normal mesenchymal stem cells (MSCs), we generated an immortalized bone marrow MSC line (hTERT-MSC). The hTERT-MSCs were exposed to plasma from healthy donors and patients with MM. Cells grown in media supplemented with plasma from MM patients failed to differentiate into OBs, while the hTERT-MSCs grown in the presence of normal human plasma generated OB clusters that mineralized calcium, expressed Runx2, and were positive for alkaline phosphatase, fibronectin, collagen I, osteocalcin, and osteopontin. Blocking Dickkopf-1 (Dkk-1) and interleukin-7 (IL-7) in MM plasma restored proper OB differentiation of hTERT-MSCs. Finally, we show that hTERT-MSCs cultured in the presence of MM plasma adopt a cancer-associated stroma phenotype. Thus, we show, that systemic factors present in the plasma of patients with MM affect the behavior of non-malignant MSCs and contribute to the sustained bone disease reported in MM.

Nierste, Brittany A; Glackin, Carlotta A; Kirshner, Julia

2014-01-01

188

Discovery and Characterization of Novel Allosteric Potentiators of M1 Muscarinic Receptors Reveals Multiple Modes of Activity  

PubMed Central

Activators of M1 muscarinic acetylcholine receptors (mAChRs) may provide novel treatments for schizophrenia and Alzheimer's disease. Unfortunately, the development of M1-active compounds has resulted in nonselective activation of the highly related M2 to M5 mAChR subtypes, which results in dose-limiting side effects. Using a functional screening approach, we identified several novel ligands that potentiated agonist activation of M1 with low micromolar potencies and induced 5-fold or greater leftward shifts of the acetylcholine (ACh) concentration-response curve. These ligands did not compete for binding at the ACh binding site, indicating that they modulate receptor activity by binding to allosteric sites. The two most selective compounds, cyclopentyl 1,6-dimethyl-4-(6-nitrobenzo[d][1,3]-dioxol-5-yl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate (VU0090157) and (E)-2-(4-ethoxyphenylamino)-N?-((2-hydroxynaphthalen-1-yl)methylene)acetohydrazide (VU0029767), induced progressive shifts in ACh affinity at M1 that were consistent with their effects in a functional assay, suggesting that the mechanism for enhancement of M1 activity by these compounds is by increasing agonist affinity. These compounds were strikingly different, however, in their ability to potentiate responses at a mutant M1 receptor with decreased affinity for ACh and in their ability to affect responses of the allosteric M1 agonist, 1-[1?-(2-tolyl)-1,4?-bipiperidin-4-yl]-1,3-dihydro-2H-benzimidazol-2-one. Furthermore, these two compounds were distinct in their abilities to potentiate M1-mediated activation of phosphoinositide hydrolysis and phospholipase D. The discovery of multiple structurally distinct positive allosteric modulators of M1 is an exciting advance in establishing the potential of allosteric modulators for selective activation of this receptor. These data also suggest that structurally diverse M1 potentiators may act by distinct mechanisms and differentially regulate receptor coupling to downstream signaling pathways. PMID:19047481

Marlo, Joy E.; Niswender, Colleen M.; Days, Emily L.; Bridges, Thomas M.; Xiang, Yun; Rodriguez, Alice L.; Shirey, Jana K.; Brady, Ashley E.; Nalywajko, Tasha; Luo, Qingwei; Austin, Cheryl A.; Williams, Michael Baxter; Kim, Kwangho; Williams, Richard; Orton, Darren; Brown, H. Alex; Lindsley, Craig W.; Weaver, C. David; Conn, P. Jeffrey

2009-01-01

189

Multidimensional partial differential equation systems: Generating new systems via conservation laws, potentials, gauges, subsystems  

NASA Astrophysics Data System (ADS)

For many systems of partial differential equations (PDEs), including nonlinear ones, one can construct nonlocally related PDE systems. In recent years, such nonlocally related systems have proven to be useful in applications. In particular, they have yielded systematically nonlocal symmetries, nonlocal conservation laws, noninvertible linearizations, and new exact solutions for many different PDE systems of interest. However, the overwhelming majority of new results and theoretical understanding pertain only to PDE systems with two independent variables. The situation for PDE systems with more than two independent variables turns out to be much more complicated due to gauge freedom relating potential variables. The current paper, together with the companion paper [A. F. Cheviakov and G. W. Bluman, J. Math. Phys. 51, 103522 (2010)], synthesizes and systematically extends known results for nonlocally related systems arising for multidimensional PDE systems, i.e., for PDE systems with three or more independent variables. The presented framework includes potential systems arising from lower-degree conservation laws of a given PDE system. Nonlocally related multidimensional PDE systems are discussed in terms of their construction, properties, and applications.

Cheviakov, Alexei F.; Bluman, George W.

2010-10-01

190

Stem Cells From Umbilical Cord Wharton’s Jelly From Preterm Birth Have Neuroglial Differentiation Potential  

PubMed Central

Objective: The aim of the study is to determine the neuroglial differentiation potential of human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) from preterm birth when compared to term delivery. Study Design: The WJ-MSCs from umbilical cords of preterm birth and term controls were isolated and induced into neural progenitors. The cells were analyzed for neuroglial markers by flow cytometry, real-time polymerase chain reaction, and immunocytochemistry. Results: Independent of gestational age, a subset of WJ-MSC displayed the neural progenitor cell markers Nestin and Musashi-1 and the mature neural markers microtubule-associated protein 2, glial fibrillary acidic protein, and myelin basic protein. Neuroglial induction of WJ-MSCs from term and preterm birth resulted in the enhanced transcription of Nestin and Musashi-1. Conclusions: Undifferentiated WJ-MSCs from preterm birth express neuroglial markers and can be successfully induced into neural progenitors similar to term controls. Their potential use as cellular graft in neuroregenerative therapy for peripartum brain injury in preterm birth has to be tested. PMID:23670950

Messerli, Marianne; Wagner, Anna; Sager, Ruth; Mueller, Martin; Baumann, Marc; Surbek, Daniel V.; Schoeberlein, Andreina

2013-01-01

191

Dietary benefits of fungal associates to an eruptive herbivore: potential implications of multiple associates on host population dynamics.  

PubMed

We used the mountain pine beetle (Dendroctonus ponderosae Hopkins) and its two fungal associates, Grosmannia clavigera and Ophiostoma montium, to study potential nutritional benefits of fungi to bark beetles. We tested for potential effects of feeding on phloem colonized by fungi on beetle performance in field and laboratory studies. The fungi increased nitrogen levels in the phloem of attacked trees by 40%, indicating that it may be an important source of dietary nitrogen for mountain pine beetles. However, nitrogen levels of phloem inoculated with fungi in the laboratory were similar to uncolonized phloem, indicating that the fungi may redistribute nitrogen from the sapwood to the phloem rather than increase absolute levels of nitrogen. Beetles emerging from attacked trees carrying G. clavigera were larger than beetles carrying O. montium, which in turn were larger than beetles lacking fungi. Results of experimental laboratory studies varied, likely because of differences in the growth and sporulation of fungi under artificial conditions. Results indicate that the two fungi may offer complementary benefits to the mountain pine beetle because larvae preferentially fed on phloem colonized by both fungi together over phloem colonized by one fungus or uncolonized phloem. Teneral adults preemergence fed on spores in pupal chambers when they were produced and consumed little phloem before emerging. Teneral adults mined extensively in the phloem before emerging when spores were not produced in the pupal chamber. Our results provide evidence for a nutritional role of fungi in the diet of bark beetles and show that multiple associates may differentially affect beetle performance, which could have important implications for bark beetle population dynamics. PMID:18284766

Bleiker, K P; Six, D L

2007-12-01

192

Multiple gamma oscillations in the brain: A new strategy to differentiate functional correlates and P300 dynamics.  

PubMed

Brain oscillations in the gamma frequency band, - i.e. oscillations greater than 25Hz - have attracted increasing attention over the last few decades in the research of sensory-cognitive processes. In the neuroscience research literature, a great number of reports aim to describe the functional correlates of oscillatory responses in the gamma frequency window. However, analysis using a broadband frequency window often leads to divergent functional interpretations and controversies. In order to provide a more exact approach, we have used a strategy by defining multiple frequency and multiple time windows according to the combined analysis of conventional power spectral windows, frequency adaptive multiple filters, and inter-trial coherence. The analysis in frequency windows of 25-30Hz, 30-35Hz, and 40-48Hz enables the investigator to provide a distinction of cognitive and/or sensory responses. Moreover, according to topological differentiation and the consideration of neuroanatomic pathways, more reliable interpretations of gamma responses are reached. PMID:25660304

Ba?ar, Erol; Tülay, Elif; Güntekin, Bahar

2015-03-01

193

Reconstruction of multiple gastric electrical wave fronts using potential-based inverse methods  

NASA Astrophysics Data System (ADS)

One approach for non-invasively characterizing gastric electrical activity, commonly used in the field of electrocardiography, involves solving an inverse problem whereby electrical potentials on the stomach surface are directly reconstructed from dense potential measurements on the skin surface. To investigate this problem, an anatomically realistic torso model and an electrical stomach model were used to simulate potentials on stomach and skin surfaces arising from normal gastric electrical activity. The effectiveness of the Greensite-Tikhonov or the Tikhonov inverse methods were compared under the presence of 10% Gaussian noise with either 84 or 204 body surface electrodes. The stability and accuracy of the Greensite-Tikhonov method were further investigated by introducing varying levels of Gaussian signal noise or by increasing or decreasing the size of the stomach by 10%. Results showed that the reconstructed solutions were able to represent the presence of propagating multiple wave fronts and the Greensite-Tikhonov method with 204 electrodes performed best (correlation coefficients of activation time: 90%; pacemaker localization error: 3 cm). The Greensite-Tikhonov method was stable with Gaussian noise levels up to 20% and 10% change in stomach size. The use of 204 rather than 84 body surface electrodes improved the performance; however, for all investigated cases, the Greensite-Tikhonov method outperformed the Tikhonov method.

Kim, J. H. K.; Pullan, A. J.; Cheng, L. K.

2012-08-01

194

Breastmilk Is a Novel Source of Stem Cells with Multilineage Differentiation Potential  

PubMed Central

The mammary gland undergoes significant remodeling during pregnancy and lactation, which is fuelled by controlled mammary stem cell (MaSC) proliferation. The scarcity of human lactating breast tissue specimens and the low numbers and quiescent state of MaSCs in the resting breast have hindered understanding of both normal MaSC dynamics and the molecular determinants that drive their aberrant self-renewal in breast cancer. Here, we demonstrate that human breastmilk contains stem cells (hBSCs) with multilineage properties. Breastmilk cells from different donors displayed variable expression of pluripotency genes normally found in human embryonic stem cells (hESCs). These genes included the transcription factors (TFs) OCT4, SOX2, NANOG, known to constitute the core self-renewal circuitry of hESCs. When cultured in the presence of mouse embryonic feeder fibroblasts, a population of hBSCs exhibited an encapsulated ESC-like colony morphology and phenotype and could be passaged in secondary and tertiary clonogenic cultures. While self-renewal TFs were found silenced in the normal resting epithelium, they were dramatically upregulated in breastmilk cells cultured in 3D spheroid conditions. Furthermore, hBSCs differentiated in vitro into cell lineages from all three germ layers. These findings provide evidence that breastmilk represents a novel and noninvasive source of patient-specific stem cells with multilineage potential and establish a method for expansion of these cells in culture. They also highlight the potential of these cells to be used as novel models to understand adult stem cell plasticity and breast cancer, with potential use in bioengineering and tissue regeneration. Stem Cells2012;30:2164–2174 PMID:22865647

Hassiotou, Foteini; Beltran, Adriana; Chetwynd, Ellen; Stuebe, Alison M; Twigger, Alecia-Jane; Metzger, Philipp; Trengove, Naomi; Lai, Ching Tat; Filgueira, Luis; Blancafort, Pilar; Hartmann, Peter E

2012-01-01

195

Can Vestibular-Evoked Myogenic Potentials Help Differentiate Ménière Disease from Vestibular Migraine?  

PubMed Central

Objectives To characterize both cervical and ocular vestibular-evoked myogenic potential (cVEMP, oVEMP) responses to air-conducted sound (ACS) and midline taps in Ménière disease (MD), vestibular migraine (VM), and controls, as well as to determine if cVEMP or oVEMP responses can differentiate MD from VM. Study Design Prospective cohort study. Setting Tertiary referral center. Subjects and Methods Unilateral definite MD patients (n = 20), VM patients (n = 21) by modified Neuhauser criteria, and age-matched controls (n = 28). cVEMP testing used ACS (clicks), and oVEMP testing used ACS (clicks and 500-Hz tone bursts) and midline tap stimuli (reflex hammer and Mini-Shaker). Outcome parameters were cVEMP peak-to-peak amplitudes and oVEMP n10 amplitudes. Results Relative to controls, MD and VM groups both showed reduced click-evoked cVEMP (P < .001) and oVEMP (P < .001) amplitudes. Only the MD group showed reduction in tone-evoked amplitudes for oVEMP. Tone-evoked oVEMPs differentiated MD from controls (P = .001) and from VM (P = .007). The oVEMPs in response to the reflex hammer and Mini-Shaker midline taps showed no differences between groups (P > .210). Conclusions Using these techniques, VM and MD behaved similarly on most of the VEMP test battery. A link in their pathophysiology may be responsible for these responses. The data suggest a difference in 500-Hz tone burst–evoked oVEMP responses between MD and MV as a group. However, no VEMP test that was investigated segregated individuals with MD from those with VM. PMID:22267492

Zuniga, M. Geraldine; Janky, Kristen L.; Schubert, Michael C.; Carey, John P.

2013-01-01

196

Human versus porcine mesenchymal stromal cells: phenotype, differentiation potential, immunomodulation and cardiac improvement after transplantation  

PubMed Central

Abstract Although mesenchymal stromal cells (MSCs) have been applied clinically to treat cardiac diseases, it is unclear how and to which extent transplanted MSCs exert their beneficial effects. To address these questions, pre-clinical MSC administrations are needed for which pigs appear to be the species of choice. This requires the use of porcine cells to prevent immune rejection. However, it is currently unknown to what extent porcine MSCs (pMSCs) resemble human MSCs (hMSCs). Aim of this study was to compare MSC from porcine bone marrow (BM) with human cells for phenotype, multi-lineage differentiation potential, immune-modulatory capacity and the effect on cardiac function after transplantation in a mouse model of myocardial infarction. Flow cytometric analysis revealed that pMSC expressed surface antigens also found on hMSC, including CD90, MSCA-1 (TNAP/W8B2 antigen), CD44, CD29 and SLA class I. Clonogenic outgrowth was significantly enriched following selection of CD271+ cells from BM of human and pig (129 ± 29 and 1961 ± 485 fold, respectively). hMSC and pMSC differentiated comparably into the adipogenic, osteogenic or chondrogenic lineages, although pMSC formed fat much faster than hMSC. Immuno-modulation, an important feature of hMSC, was clearly demonstrated for pMSC when co-cultured with porcine peripheral blood cells stimulated with PMA and pIL-2. Finally, pMSC transplantation after myocardial infarction attenuated adverse remodelling to a similar extent as hMSC when compared to control saline injection. These findings demonstrate that pMSCs have comparable characteristics and functionality with hMSCs, making reliable extrapolation of pre-clinical pMSC studies into a clinical setting very well possible. PMID:21973026

Noort, W A; Oerlemans, M I F J; Rozemuller, H; Feyen, D; Jaksani, S; Stecher, D; Naaijkens, B; Martens, A C; Bühring, H J; Doevendans, P A; Sluijter, J P G

2012-01-01

197

Potential multiple steady-states in the long-term carbon cycle  

E-print Network

Modelers of the long term carbon cycle in Earth history have previously assumed there is only one stable climatic steady state. Here we investigate the possibility of multiple steady states. We find them in Abiotic World, lacking any biotic influence, resulting from possible variations in planetary albedo in different temperature, atmospheric carbon dioxide level regimes, with the same weathering forcing balancing a volcanic source to the atmosphere, ocean pool. In Plant World modeling relevant to the Phanerozoic, we include the additional effects of biotic enhancement of weathering on land, organic carbon burial, oxidation of reduced organic carbon in terrestrial sediments and the variation of biotic productivity with temperature, finding a second stable steady state appearing between twenty and fifty degrees C. The very warm early Triassic climate may be the prime candidate for an upper temperature steady state. Given our results, the anthropogenic driven rise of atmospheric carbon dioxide could potentially...

Tennenbaum, Stephen; Schwartzman, David

2013-01-01

198

Perceived stress in multiple sclerosis: The potential role of mindfulness in health and wellbeing  

PubMed Central

Stressful life events are associated with worsening neurological symptoms and decreased quality of life in multiple sclerosis (MS). Mindful-consciousness can alter the impact of stressful events and has potential to improve health outcomes in MS. This study evaluated the relationship between trait mindfulness and perceived stress, coping, and resilience in people with MS. Quality of life was assessed as a secondary outcome. 119 people with confirmed MS completed the Five-facet Mindfulness Questionnaire, Perceived Stress Scale, Brief Coping Orientation for Problem Experiences, Connor-Davidson Resilience Scale, and the SF-36. Greater trait mindfulness was significantly associated with decreased psychological stress, better coping skills, increased resilience, and higher quality of life. After controlling for confounders, mindfulness accounted for 25% of the variation in perceived stress scores and 44% of the variation in resilience scores. Results support further investigation of mindfulness training to enhance psychological resilience and improve wellbeing for those living with MS. PMID:24647090

Senders, Angela; Bourdette, Dennis; Hanes, Douglas; Yadav, Vijayshree; Shinto, Lynne

2014-01-01

199

Multiple pathways are involved in DNA degradation during keratinocyte terminal differentiation  

PubMed Central

Loss of the nucleus is a critical step in keratinocyte terminal differentiation. To elucidate the mechanisms involved, we focused on two characteristic events: nuclear translocation of N-terminal fragment of profilaggrin and caspase-14-dependent degradation of the inhibitor of caspase-activated DNase (ICAD). First, we demonstrated that epidermal mesotrypsin liberated a 55-kDa N-terminal fragment of profilaggrin (FLG-N) and FLG-N was translocated into the nucleus. Interestingly, these cells became TUNEL positive. Mutation in the mesotrypsin-susceptible Arg-rich region between FLG-N and the first filaggrin domain abolished these changes. Furthermore, caspase-14 caused limited proteolysis of ICAD, followed by accumulation of caspase-activated DNase (CAD) in TUNEL-positive nuclei. Knockdown of both proteases resulted in a significant increase of remnant nuclei in a skin equivalent model. Immunohistochemical study revealed that both caspase-14 and mesotrypsin were markedly downregulated in parakeratotic areas of lesional skin from patients with atopic dermatitis and psoriasis. Collectively, our results indicate that at least two pathways are involved in the DNA degradation process during keratinocyte terminal differentiation. PMID:24743736

Yamamoto-Tanaka, M; Makino, T; Motoyama, A; Miyai, M; Tsuboi, R; Hibino, T

2014-01-01

200

Formation Control and Obstacle Avoidance Algorithm of Multiple Autonomous Underwater Vehicles(AUVs) Based on Potential Function and Behavior Rules  

Microsoft Academic Search

A new control algorithm based on potential function and behavior rules to effectively control the formation of a multiple autonomous underwater vehicle (AUV) system under uncertain environment and to make the formation effectively avoid obstacles is presented. Proper potential functions concerning with object, obstacle and the structure of the formation is chosen to design a new distributed control algorithm to

Qiuling Jia; Guangwen Li

2007-01-01

201

Gluteal and abdominal subcutaneous adipose tissue depots as stroma cell source: gluteal cells display increased adipogenic and osteogenic differentiation potentials.  

PubMed

Human adipose-derived stroma cells (ADSCs) have successfully been employed in explorative therapeutic studies. Current evidence suggests that ADSCs are unevenly distributed in subcutaneous adipose tissue; therefore, the anatomical origin of ADSCs may influence clinical outcomes. This study was designed to investigate proliferation and differentiation capacities of ADSCs from the gluteal and abdominal depot of 8 females. All had normal BMI (22.01 ± 0.39 kg/m(2) ) and waist circumference (81.13 ± 2.33 cm). Examination by physicians and analysis of 31 laboratory parameters did not reveal possibly confounding medical disorders. Gluteal and abdominal adipose tissue was sampled by en bloc resection on day 7 (±1) after the last menses. Histological examination did not reveal significant depot-specific differences. As assessed by BrdU assay, proliferation of cells from both depots was similar after 24 h and analysis of 15 cell surface markers by flow cytometry identified the isolated cells as ADSCs, again without depot-specific differences. ADSCs from both depots differentiated poorly to chondroblasts. Gluteal ADSCs displayed significantly higher adipogenic differentiation potential than abdominal cells. Osteogenic differentiation was most pronounced in gluteal cells, whereas differentiation of abdominal ADSCs was severely impaired. Our data demonstrate a depot-specific difference in ADSC differentiation potential with abdominal cells failing to meet the criteria of multipotent ADSCs. This finding should be taken into account in future explorations of ADSC-derived therapeutic strategies. PMID:24689514

Iwen, Karl Alexander; Priewe, Anna-Christin; Winnefeld, Marc; Rose, Christian; Siemers, Frank; Rohwedel, Jürgen; Cakiroglu, Figen; Lehnert, Hendrik; Schepky, Andreas; Klein, Johannes; Kramer, Jan

2014-06-01

202

Optical zero-differential pressure switch and its evaluation in a multiple pressure measuring system  

NASA Technical Reports Server (NTRS)

The design of a clamped-diaphragm pressure switch is described in which diaphragm motion is detected by a simple fiber-optic displacement sensor. The switch was evaluated in a pressure measurement system where it detected the zero crossing of the differential pressure between a static test pressure and a tank pressure that was periodically ramped from near zero to fullscale gage pressure. With a ramping frequency of 1 hertz and a full-scale tank pressure of 69 N/sq cm gage (100 psig), the switch delay was as long as 2 milliseconds. Pressure measurement accuracies were 0.25 to 0.75 percent of full scale. Factors affecting switch performance are also discussed.

Powell, J. A.

1977-01-01

203

[White matter lesions, young age, female--differential diagnosis of multiple sclerosis and juvenile stroke].  

PubMed

Fabry's disease is an X-chromosomal linked recessive lysosomal storage disease caused by a deficiency of ?-galactosidase A. Accumulation of toxic levels of sphingolipids leads to metabolic dysfunction in various cell types (endothelial cells, myocytes, fibroblasts) and organs thus causing a variety of symptoms. Neurological manifestations include recurrent strokes and polyneuropathy, many patients complain of pain or vertigo. The presentation of these polymorphic symptoms mostly at young age often leads to incorrect diagnosis and mistreatment. Here we report two cases of female patients who both were misdiagnosed and thus mistreated for many years. These case-reports aim in increasing the awareness for Fabry's disease as a differential diagnosis, especially in young women presenting with white matter lesions. PMID:23516103

Flossdorf, P; Kurschat, C; Fink, G R; Sparing, R

2013-03-01

204

The SWI/SNF Chromatin Remodeling Complex Selectively Affects Multiple Aspects of Serotonergic Neuron Differentiation  

PubMed Central

Regulatory programs that control the specification of serotonergic neurons have been investigated by genetic mutant screens in the nematode Caenorhabditis elegans. Loss of a previously uncloned gene, ham-3, affects migration and serotonin antibody staining of the hermaphrodite-specific neuron (HSN) pair. We characterize these defects here in more detail, showing that the defects in serotonin antibody staining are paralleled by a loss of the transcription of all genes involved in serotonin synthesis and transport. This loss is specific to the HSN class as other serotonergic neurons appear to differentiate normally in ham-3 null mutants. Besides failing to migrate appropriately, the HSNs also display axon pathfinding defects in ham-3 mutants. However, the HSNs are still generated and express a subset of their terminal differentiation features in ham-3 null mutants, demonstrating that ham-3 is a specific regulator of select features of the HSNs. We show that ham-3 codes for the C. elegans ortholog of human BAF60, Drosophila Bap60, and yeast Swp73/Rsc6, which are subunits of the yeast SWI/SNF and vertebrate BAF chromatin remodeling complex. We show that the effect of ham-3 on serotonergic fate can be explained by ham-3 regulating the expression of the Spalt/SALL-type Zn finger transcription factor sem-4, a previously identified regulator of serotonin expression in HSNs and of the ham-2 Zn transcription factor, a previously identified regulator of HSN migration and axon outgrowth. Our findings provide the first evidence for the involvement of the BAF complex in the acquisition of terminal neuronal identity and constitute genetic proof by germline knockout that a BAF complex component can have cell-type-specific roles during development. PMID:23457234

Weinberg, Peter; Flames, Nuria; Sawa, Hitoshi; Garriga, Gian; Hobert, Oliver

2013-01-01

205

Method and system for measuring multiphase flow using multiple pressure differentials  

DOEpatents

An improved method and system for measuring a multiphase flow in a pressure flow meter. An extended throat venturi is used and pressure of the multiphase flow is measured at three or more positions in the venturi, which define two or more pressure differentials in the flow conduit. The differential pressures are then used to calculate the mass flow of the gas phase, the total mass flow, and the liquid phase. The method for determining the mass flow of the high void fraction fluid flow and the gas flow includes certain steps. The first step is calculating a gas density for the gas flow. The next two steps are finding a normalized gas mass flow rate through the venturi and computing a gas mass flow rate. The following step is estimating the gas velocity in the venturi tube throat. The next step is calculating the pressure drop experienced by the gas-phase due to work performed by the gas phase in accelerating the liquid phase between the upstream pressure measuring point and the pressure measuring point in the venturi throat. Another step is estimating the liquid velocity in the venturi throat using the calculated pressure drop experienced by the gas-phase due to work performed by the gas phase. Then the friction is computed between the liquid phase and a wall in the venturi tube. Finally, the total mass flow rate based on measured pressure in the venturi throat is calculated, and the mass flow rate of the liquid phase is calculated from the difference of the total mass flow rate and the gas mass flow rate.

Fincke, James R. (Idaho Falls, ID)

2001-01-01

206

Medicago truncatula symbiotic peptide NCR247 contributes to bacteroid differentiation through multiple mechanisms.  

PubMed

Symbiosis between rhizobia soil bacteria and legume plants results in the formation of root nodules where plant cells are fully packed with nitrogen fixing bacteria. In the host cells, the bacteria adapt to the intracellular environment and gain the ability for nitrogen fixation. Depending on the host plants, the symbiotic fate of bacteria can be either reversible or irreversible. In Medicago and related legume species, the bacteria undergo a host-directed multistep differentiation process culminating in the formation of elongated and branched polyploid bacteria with definitive loss of cell division ability. The plant factors are nodule-specific symbiotic peptides. Approximately 600 of them are nodule-specific cysteine-rich (NCR) peptides produced in the rhizobium-infected plant cells. NCRs are targeted to the endosymbionts, and concerted action of different sets of peptides governs different stages of endosymbiont maturation, whereas the symbiotic function of individual NCRs is unknown. This study focused on NCR247, a cationic peptide exhibiting in vitro antimicrobial activities. We show that NCR247 acts in those nodule cells where bacterial cell division is arrested and cell elongation begins. NCR247 penetrates the bacteria and forms complexes with many bacterial proteins. Interaction with FtsZ required for septum formation is one of the host interventions for inhibiting bacterial cell division. Complex formation with the ribosomal proteins affects translation and contributes to altered proteome and physiology of the endosymbiont. Binding to the chaperone GroEL amplifies the NCR247-modulated biological processes. We show that GroEL1 of Sinorhizobium meliloti is required for efficient infection, terminal differentiation, and nitrogen fixation. PMID:24706863

Farkas, Attila; Maróti, Gergely; Durg?, Hajnalka; Györgypál, Zoltán; Lima, Rui M; Medzihradszky, Katalin F; Kereszt, Attila; Mergaert, Peter; Kondorosi, Éva

2014-04-01

207

Review of daclizumab and its therapeutic potential in the treatment of relapsing–remitting multiple sclerosis  

PubMed Central

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. It can present in several forms, with the relapsing–remitting pattern being the most common. Since the approval of the first disease-modifying therapy and the initiation of appropriate treatments from the early stages of the disease, there seem to be positive impacts on the long-term outcomes and disability associated with MS. Currently, there are ten approved drugs for the treatment of MS, and several more are in various stages of development. These medications each have their unique profile in terms of efficacy, dose, routes of administration, tolerability, and adverse effects. Daclizumab is a humanized monoclonal antibody that is being explored for the treatment of MS. It is currently approved for use in allograft renal transplantation. Given its modulatory effects on the immune system, daclizumab’s potential for use in MS was tested in extensive Phase II trials. With continued demonstration of its efficacy, it is currently in a Phase III trial for relapsing–remitting MS. While daclizumab has demonstrated beneficial effects in controlling disease activity in MS, there were also some safety and tolerability concerns that were raised. Further information from the ongoing Phase III trial, and from open-label studies, will shed light on the benefit and risk profile of this drug and its potential for use in MS. PMID:24143075

Reardon, Jennifer; Perumal, Jai S

2013-01-01

208

Amyloid imaging in the differential diagnosis of dementia: review and potential clinical applications  

PubMed Central

In the past decade, positron emission tomography (PET) with carbon-11-labeled Pittsburgh Compound B (PIB) has revolutionized the neuroimaging of aging and dementia by enabling in vivo detection of amyloid plaques, a core pathologic feature of Alzheimer's disease (AD). Studies suggest that PIB-PET is sensitive for AD pathology, can distinguish AD from non-AD dementia (for example, frontotemporal lobar degeneration), and can help determine whether mild cognitive impairment is due to AD. Although the short half-life of the carbon-11 radiolabel has thus far limited the use of PIB to research, a second generation of tracers labeled with fluorine-18 has made it possible for amyloid PET to enter the clinical era. In the present review, we summarize the literature on amyloid imaging in a range of neurodegenerative conditions. We focus on potential clinical applications of amyloid PET and its role in the differential diagnosis of dementia. We suggest that amyloid imaging will be particularly useful in the evaluation of mildly affected, clinically atypical or early age-at-onset patients, and illustrate this with case vignettes from our practice. We emphasize that amyloid imaging should supplement (not replace) a detailed clinical evaluation. We caution against screening asymptomatic individuals, and discuss the limited positive predictive value in older populations. Finally, we review limitations and unresolved questions related to this exciting new technique. PMID:22071129

2011-01-01

209

Multiple electron loss cross sections for heavy ions incident on various atomic and molecular gases. [Differential and total cross sections, charge exchange, 20 MeV  

Microsoft Academic Search

Differential cross sections for charge change resulting from the scattering of 20 MeV ¹²⁷I\\/sup 5 +\\/ and 20 MeV ³⁵Cl\\/sup 4 +\\/ ions from thin gaseous targets were measured. Total cross sections for multiple electron loss were determined by integration of the differential charge state yields over angle. Cross sections will be presented for ¹²⁷I\\/sup 5 +\\/ ions and ³⁵Cl\\/sup

1978-01-01

210

Investigation of Adjustable Current-Voltage Characteristics and Hysteresis Phenomena for Multiple-Peak Negative Differential Resistance Circuit  

NASA Astrophysics Data System (ADS)

A multiple-peak negative differential resistance (NDR) circuit made of standard Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and SiGe-based heterojunction bipolar transistor (HBT) is demonstrated. We can obtain a three-peak I-V curve by connecting three cascoded MOS-HBT-NDR circuits by suitably designing the MOS parameters. This novel three-peak NDR circuit possesses the adjustable current-voltage characteristics and high peak-to-valley current ratio (PVCR). We can adjust the PVCR values to be as high as 11.5, 6.5, and 10.3 for three peaks, respectively. Because the NDR circuit is a very strong nonlinear element, we discuss the extrinsic hysteresis phenomena in this multiple-peak NDR circuit. The effect of series resistance on hysteresis phenomena is also investigated. Our design and fabrication of the NDR circuit is based on the standard 0.35?m SiGe BiCMOS process.

Gan, Kwang-Jow; Liang, Dong-Shong

211

Multiple evolutionary processes drive the patterns of genetic differentiation in a forest tree species complex  

PubMed Central

Forest trees frequently form species complexes, complicating taxonomic classification and gene pool management. This is certainly the case in Eucalyptus, and well exemplified by the Eucalyptus globulus complex. This ecologically and economically significant complex comprises four taxa (sspp. bicostata, globulus, maidenii, pseudoglobulus) that are geographically and morphologically distinct, but linked by extensive “intergrade” populations. To resolve their genetic affinities, nine microsatellites were used to genotype 1200 trees from throughout the natural range of the complex in Australia, representing 33 morphological core and intergrade populations. There was significant spatial genetic structure (FST = 0.10), but variation was continuous. High genetic diversity in southern ssp. maidenii indicates that this region is the center of origin. Genetic diversity decreases and population differentiation increases with distance from this area, suggesting that drift is a major evolutionary process. Many of the intergrade populations, along with other populations morphologically classified as ssp. pseudoglobulus or ssp. globulus, belong to a “cryptic genetic entity” that is genetically and geographically intermediate between core ssp. bicostata, ssp. maidenii, and ssp. globulus. Geography, rather than morphology, therefore, is the best predictor of overall genetic affinities within the complex and should be used to classify germplasm into management units for conservation and breeding purposes. PMID:23403692

Jones, Rebecca C; Steane, Dorothy A; Lavery, Martyn; Vaillancourt, René E; Potts, Brad M

2013-01-01

212

Geochemical consequences of flow differentiation in a multiple injection dike (Trinity ophiolite, N. California)  

USGS Publications Warehouse

A clinopyroxene-rich dike of the Trinity ophiolite sheeted-dike complex shows three different magmatic pulses, probably injected in a short period of time (no well developed chilled margin) and important variations of the clinopyroxene and plagioclase percentages between its core (highly porphyritic) and margins (aphyric). This variation, interpreted as related to a flow differentiation phenomenon (mechanical phenocryst redistribution), has important geochemical consequences. It produces increases in the FeO, MgO, CaO, Cr and Ni contents from the margin to the core, together with increases in the clinopyroxene percentage, and decreases in the SiO2, Zr, Y, Nb and REE contents together with a decrease in the percentage of the fine-grained groundmass toward the core of the dike. This mineralogical redistribution, which also affects the incompatible trace element ratios because of the difference in plagioclase and clinopyroxene mineral/liquid partition coefficients, illustrate the importance of fractionation processes outside of a magma chamber. ?? 1991.

Brouxel, M.

1991-01-01

213

Developing Multiple Diverse Potential Designs for Heat Transfer Utilizing Graph Based Evolutionary Algorithms  

SciTech Connect

This paper examines the use of graph based evolutionary algorithms (GBEAs) to find multiple acceptable solutions for heat transfer in engineering systems during the optimization process. GBEAs are a type of evolutionary algorithm (EA) in which a topology, or geography, is imposed on an evolving population of solutions. The rates at which solutions can spread within the population are controlled by the choice of topology. As in nature geography can be used to develop and sustain diversity within the solution population. Altering the choice of graph can create a more or less diverse population of potential solutions. The choice of graph can also affect the convergence rate for the EA and the number of mating events required for convergence. The engineering system examined in this paper is a biomass fueled cookstove used in developing nations for household cooking. In this cookstove wood is combusted in a small combustion chamber and the resulting hot gases are utilized to heat the stove’s cooking surface. The spatial temperature profile of the cooking surface is determined by a series of baffles that direct the flow of hot gases. The optimization goal is to find baffle configurations that provide an even temperature distribution on the cooking surface. Often in engineering, the goal of optimization is not to find the single optimum solution but rather to identify a number of good solutions that can be used as a starting point for detailed engineering design. Because of this a key aspect of evolutionary optimization is the diversity of the solutions found. The key conclusion in this paper is that GBEA’s can be used to create multiple good solutions needed to support engineering design.

David J. Muth Jr.

2006-09-01

214

Acupuncture: a potential modality for the treatment of auricular pruritus in ramsay hunt syndrome with multiple cranial nerve lesions.  

PubMed

Auricular pruritus coexisted with multiple cranial nerve lesions in Ramsay Hunt syndrome has been rarely reported in the literature especially its treatment. However, auricular pruritus cannot be better improved along with the improvement of multiple cranial nerve lesions. We tried to solve the problem with acupuncture and got experience from it. The following 2 cases of Ramsay Hunt syndromeshow a potential modality for the treatment of auricular prurituswith acupuncture. PMID:25710744

Liu, Lan Ying; Wang, He Sheng; Sun, Jian Hua

2015-03-01

215

Gender as a differential indicator of the employment discrimination experiences of Americans with multiple sclerosis.  

PubMed

Information from the Integrated Mission System of the United States Equal Employment Opportunity Commission (EEOC) was used to investigate the employment discrimination experiences of women and men with multiple sclerosis (MS). Spanning the years 1992 to 2003, the EEOC database included 3,663 allegations of discrimination filed by 2,167 adults with MS. With respect to women and men with MS, the researchers examined the comparability of a) demographic characteristics; b) industry designations, locations, and size of employers; c) the nature of discrimination alleged; and d) the legal outcome or resolution of those allegations. On average, women and men with MS were in their early forties, with the majority of both groups being Caucasian. Both women and men were most likely to allege discrimination related to discharge and reasonable accommodations, although women were more likely to file harassment charges than men. Men with MS were more likely to allege discrimination regarding hiring and reinstatement. Women with MS were more likely to file allegations against employers in the service industries, and men were more likely to file allegations against employers in the construction, manufacturing, and wholesale industries. No gender differences were found in the geographic distribution of allegations. Both groups had comparable rates of merit closures (23% vs. 27%) as a result of the EEOC's investigatory process. Implications for rehabilitation counseling and employer-oriented interventions are discussed. PMID:18057570

Rumrill, Phillip D; Roessler, Richard T; McMahon, Brian T; Hennessey, Mary L; Neath, Jeanne

2007-01-01

216

Multiple Sources of Striatal Inhibition Are Differentially Affected in Huntington’s Disease Mouse Models  

PubMed Central

In Huntington’s disease (HD) mouse models, spontaneous inhibitory synaptic activity is enhanced in a subpopulation of medium-sized spiny neurons (MSNs), which could dampen striatal output. We examined the potential source(s) of increased inhibition using electrophysiological and optogenetic methods to assess feedback and feedforward inhibition in two transgenic mouse models of HD. Single whole-cell patch-clamp recordings demonstrated that increased GABA synaptic activity impinges principally on indirect pathway MSNs. Dual patch recordings between MSNs demonstrated reduced connectivity between MSNs in HD mice. However, while connectivity was strictly unidirectional in controls, in HD mice bidirectional connectivity occurred. Other sources of increased GABA activity in MSNs also were identified. Dual patch recordings from fast spiking (FS) interneuron–MSN pairs demonstrated greater but variable amplitude responses in MSNs. In agreement, selective optogenetic stimulation of parvalbumin-expressing, FS interneurons induced significantly larger amplitude MSN responses in HD compared with control mice. While there were no differences in responses of MSNs evoked by activating single persistent low-threshold spiking (PLTS) interneurons in recorded pairs, these interneurons fired more action potentials in both HD models, providing another source for increased frequency of spontaneous GABA synaptic activity in MSNs. Selective optogenetic stimulation of somatostatin-expressing, PLTS interneurons did not reveal any significant differences in responses of MSNs in HD mice. These findings provide strong evidence that both feedforward and to a lesser extent feedback inhibition to MSNs in HD can potentially be sources for the increased GABA synaptic activity of indirect pathway MSNs. PMID:23616545

Cepeda, Carlos; Galvan, Laurie; Holley, Sandra M.; Rao, Shilpa P.; André, Véronique M.; Botelho, Elian P.; Chen, Jane Y.; Watson, Joseph B.; Deisseroth, Karl; Levine, Michael S.

2013-01-01

217

Differential pulse amplitude modulation for multiple-input single-output OWVLC  

NASA Astrophysics Data System (ADS)

White light-emitting diodes (LEDs) are widely used for lighting due to their energy efficiency, eco-friendly, and small size than previously light sources such as incandescent, fluorescent bulbs and so on. Optical wireless visible light communication (OWVLC) based on LED merges lighting and communications in applications such as indoor lighting, traffic signals, vehicles, and underwater communications because LED can be easily modulated. However, physical bandwidth of LED is limited about several MHz by slow time constant of the phosphor and characteristics of device. Therefore, using the simplest modulation format which is non-return-zero on-off-keying (NRZ-OOK), the data rate reaches only to dozens Mbit/s. Thus, to improve the transmission capacity, optical filtering and pre-, post-equalizer are adapted. Also, high-speed wireless connectivity is implemented using spectrally efficient modulation methods: orthogonal frequency division multiplexing (OFDM) or discrete multi-tone (DMT). However, these modulation methods need additional digital signal processing such as FFT and IFFT, thus complexity of transmitter and receiver is increasing. To reduce the complexity of transmitter and receiver, we proposed a novel modulation scheme which is named differential pulse amplitude modulation. The proposed modulation scheme transmits different NRZ-OOK signals with same amplitude and unit time delay using each LED chip, respectively. The `N' parallel signals from LEDs are overlapped and directly detected at optical receiver. Received signal is demodulated by power difference between unit time slots. The proposed scheme can overcome the bandwidth limitation of LEDs and data rate can be improved according to number of LEDs without complex digital signal processing.

Yang, S. H.; Kwon, D. H.; Kim, S. J.; Son, Y. H.; Han, S. K.

2015-01-01

218

Differential regulation by multiple promoters of the gene encoding the neuron-restrictive silencer factor  

PubMed Central

NRSF/REST is a protein that silences transcription of a number of genes that contain a DNA element called the neuron-restrictive silencer element (NRSE). During embryogenesis, REST is expressed ubiquitously in nonneural cells, but is down-regulated during differentiation of neural progenitors into neurons. REST is also up-regulated in adult neurons by activity, suggesting a possible role for the protein in synaptic plasticity. To understand mechanisms that control expression of REST, we identified and characterized the promoter region of the mouse REST gene (mREST). A 4.5-kb DNA segment containing three exons (A, B, and C) that correspond to alternatively spliced 5? untranslated regions (5?UTRs) was isolated and its DNA sequence was determined. Reverse transcription-PCR analyses of fibroblasts, astrocytes, and neural progenitors identified variants in which these exons were spliced to exon D, suggesting that exons A, B, and C may each have a promoter. Consistent with this hypothesis, primer extension and in vitro transcription experiments revealed clusters of RNA transcription initiation sites upstream of exons A, B, and C. Tests of REST/luciferase reporter constructs in Neuro2A and NIH 3T3 cells revealed promoters upstream of exons A and B that were active in both cell lines, and a promoter upstream of exon C that was weakly active only in NIH 3T3 cells. Six enhancer and two repressor regions were found to overlap each of the three promoters, and some of these were found to be cell type-specific. Combinatorial arrangements of these promoters with enhancer and repressor regions may allow modulation of REST expression in particular contexts. PMID:10688910

Koenigsberger, Carol; Chicca, John J.; Amoureux, Marie-Claude; Edelman, Gerald M.; Jones, Frederick S.

2000-01-01

219

Bone-derived mesenchymal stromal cells from HIV transgenic mice exhibit altered proliferation, differentiation capacity and paracrine functions along with impaired therapeutic potential in kidney injury  

SciTech Connect

Mesenchymal stem cells (MSCs) secrete paracrine factors that could be cytoprotective and serve roles in immunoregulation during tissue injury. Although MSCs express HIV receptors, and co-receptors, and are susceptible to HIV infection, whether HIV-1 may affect biological properties of MSCs needs more study. We evaluated cellular proliferation, differentiation and paracrine functions of MSCs isolated from compact bones of healthy control mice and Tg26 HIV-1 transgenic mice. The ability of MSCs to protect against cisplatin toxicity was studied in cultured renal tubular cells as well as in intact mice. We successfully isolated MSCs from healthy mice and Tg26 HIV-1 transgenic mice and found the latter expressed viral Nef, Vpu, NL4-3 and Vif genes. The proliferation and differentiation of Tg26 HIV-1 MSCs was inferior to MSCs from healthy mice. Moreover, transplantation of Tg26 HIV-1 MSCs less effectively improved outcomes compared with healthy MSCs in mice with acute kidney injury. Also, Tg26 HIV-1 MSCs secreted multiple cytokines, but at significantly lower levels than healthy MSCs, which resulted in failure of conditioned medium from these MSCs to protect cultured renal tubular cells from cisplatin toxicity. Therefore, HIV-1 had adverse biological effects on MSCs extending to their proliferation, differentiation, function, and therapeutic potential. These findings will help in advancing mechanistical insight in renal injury and repair in the setting of HIV-1 infection. -- Highlights: •MSCs isolated from HIV mice displayed HIV genes. •MSCs isolated from HIV mice exhibited attenuated growth and paracrine functions. •AKI mice with transplanted HIV-MSC displayed poor outcome. •HIV-1 MSC secreted multiple cytokines but at a lower level.

Cheng, Kang; Rai, Partab; Lan, Xiqian; Plagov, Andrei; Malhotra, Ashwani [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States); Gupta, Sanjeev [Departments of Medicine and Pathology, Marion Bessin Liver Research Center, Diabetes Center, Cancer Center, Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research, Institute for Clinical and Translational Research, Albert Einstein College of Medicine, Bronx, NY (United States); Singhal, Pravin C., E-mail: psinghal@nshs.edu [Feinstein Institute for Medical Research, North Shore-Long Island Jewish Health System, Manhassett, NY (United States)

2013-08-15

220

Endothelium Trans Differentiated from Wharton's Jelly Mesenchymal Cells Promote Tissue Regeneration: Potential Role of Soluble Pro-Angiogenic Factors  

PubMed Central

Background Mesenchymal stem cells have a high capacity for trans-differentiation toward many adult cell types, including endothelial cells. Feto-placental tissue, such as Wharton's jelly is a potential source of mesenchymal stem cells with low immunogenic capacity; make them an excellent source of progenitor cells with a potential use for tissue repair. We evaluated whether administration of endothelial cells derived from mesenchymal stem cells isolated from Wharton's jelly (hWMSCs) can accelerate tissue repair in vivo. Methods Mesenchymal stem cells were isolated from human Wharton's jelly by digestion with collagenase type I. Endothelial trans-differentiation was induced for 14 (hWMSC-End14d) and 30 (hWMSC-End30d) days. Cell phenotyping was performed using mesenchymal (CD90, CD73, CD105) and endothelial (Tie-2, KDR, eNOS, ICAM-1) markers. Endothelial trans-differentiation was demonstrated by the expression of endothelial markers and their ability to synthesize nitric oxide (NO). Results hWMSCs can be differentiated into adipocytes, osteocytes, chondrocytes and endothelial cells. Moreover, these cells show high expression of CD73, CD90 and CD105 but low expression of endothelial markers prior to differentiation. hWMSCs-End express high levels of endothelial markers at 14 and 30 days of culture, and also they can synthesize NO. Injection of hWMSC-End30d in a mouse model of skin injury significantly accelerated wound healing compared with animals injected with undifferentiated hWMSC or injected with vehicle alone. These effects were also observed in animals that received conditioned media from hWMSC-End30d cultures. Conclusion These results demonstrate that mesenchymal stem cells isolated from Wharton's jelly can be cultured in vitro and trans-differentiated into endothelial cells. Differentiated hWMSC-End may promote neovascularization and tissue repair in vivo through the secretion of soluble pro-angiogenic factors. PMID:25412260

Aguilera, Valeria; Briceño, Luis; Contreras, Hector; Lamperti, Liliana; Sepúlveda, Esperanza; Díaz-Perez, Francisca; León, Marcelo; Veas, Carlos; Maura, Rafael; Toledo, Jorge Roberto; Fernández, Paulina; Covarrubias, Ambart; Zuñiga, Felipe Andrés; Radojkovic, Claudia; Escudero, Carlos; Aguayo, Claudio

2014-01-01

221

Comparison of differentiation potential of male mouse adipose tissue and bone marrow derived-mesenchymal stem cells into germ cells  

PubMed Central

Background: Recent publications about differentiation of stem cells to germ cells have motivated researchers to make new approaches to infertility. In vitro production of germ cells improves understanding differentiation process of male and female germ cells. Due to the problem of using embryonic stem cells (ESC), it’s necessary the mentioned cells be replaced with some adult multi-potent stem cells in laboratories. Objective: The aim of this study was to obtain germ cells from appropriate source beyond ESC and compare differential potentials of adipocytes derived stem cells (ADMSCs) with bone marrow derived stem cells (BMMSCs). Materials and Methods: To find multi-potential entity, after providing purified ADMSCs and BMMSCs, differentiation to osteoblast and adipocyte was confirmed by using appropriate culture medium. To confirm mesenchymal lineage production superficial markers (expression of CD90 and CD44 and non-expression of CD45 and CD31) were investigated by flowcytometry. Then the cells were differentiated to germ cells in inductive medium containing retinoic acid for 7days. To evaluate germ cells characteristic markers [Dazl (Deleted in azoospermia-like), Mvh (Mouse vasa homolog gene), Stra8 (Stimulated by retinoic acid) and Scp3 (Synaptonemal complex protein 3)] flowcytometry, imunoflorescence and real time PCR were used. Results: Both types of cells were able to differentiate into osteoblast and adipocyte cells and presentation of stem cell superficial markers (CD90, CD44) and absence of endothelial and blood cell markers (CD31, CD45) were confirmative The flowcytometry, imunoflorescence and real time PCR results showed remarkable expression of germ cells characteristic markers (Mvh, Dazl, Stra8, and Scp3). Conclusion: It was found that although ADMSCs were attained easier and also cultured and differentiated rapidly, germ cell markers were expressed in BMMSCs significantly more than ADMSCs. This article extracted from M.Sc. thesis. (Maryam Hosseinzadeh Shirzeily) PMID:24639722

Hosseinzadeh Shirzeily, Maryam; Pasbakhsh, Parichehr; Amidi, Fardin; Mehrannia, Kobra; Sobhani, Aligholi

2013-01-01

222

Age-differential effects on updating cue information: evidence from event-related potentials.  

PubMed

Recent models on cognitive aging consider the ability to maintain and update context information to be a key source of age-related impairments in various cognitive tasks (Braver & Barch in Neuroscience & Biobehavioral Reviews, 26: 809-817, 2002). Context updating has been investigated with a modified AX-continuous-performance task by comparing performance and brain activity between context-dependent trials (i.e., correct responses require updating of the preceding cue information) and context-independent trials (i.e., correct responses are independent of cue information). We used an event-related potential (ERP) approach to identify sources of age differences in context processing in the early and late processing of cue information. Our behavioral data showed longer latencies and higher error rates on context-dependent than on context-independent trials for older than for younger adults, suggesting age-related impairments in context updating. The ERP data revealed larger P3b amplitudes for context-dependent than for context-independent trials only in younger adults. In contrast, in older adults, P3b amplitudes were more evenly distributed across the scalp and did not differ between context conditions. Interestingly, older but not younger adults were sensitive to changes of cue identity, as indicated by larger P3b amplitudes on cue-change than on cue-repeat trials, irrespective of the actual context condition. We also found a larger CNV on context-dependent than on context-independent trials, reflecting active maintenance of context information and response preparation. The age-differential effects in the P3b suggest that both younger and older adults were engaged in updating task-relevant information, but relied on different information: Whereas younger participants indeed relied on context cues to update and reconfigure the task settings, older adults relied on changes in cue identity, irrespective of context information. PMID:24590394

Schmitt, Hannah; Ferdinand, Nicola K; Kray, Jutta

2014-09-01

223

Differential expression of canonical (classical) transient receptor potential channels in guinea pig enteric nervous system.  

PubMed

The canonical transient receptor potential (TRPC) family of ion channels is implicated in many neuronal processes including calcium homeostasis, membrane excitability, synaptic transmission, and axon guidance. TRPC channels are postulated to be important in the functional neurobiology of the enteric nervous system (ENS); nevertheless, details for expression in the ENS are lacking. Reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemistry were used to study the expression and localization of TRPC channels. We found mRNA transcripts, protein on Western blots, and immunoreactivity (IR) for TRPC1/3/4/6 expressed in the small intestinal ENS of adult guinea pigs. TRPC1/3/4/6-IR was localized to distinct subpopulations of enteric neurons and was differentially distributed between the myenteric and submucosal divisions of the ENS. TRPC1-IR was widely distributed and localized to neurons with cholinergic, calretinin, and nitrergic neuronal immunochemical codes in the myenteric plexus. It was localized to both cholinergic and noncholinergic secretomotor neurons in the submucosal plexus. TRPC3-IR was found only in the submucosal plexus and was expressed exclusively by neuropeptide Y-IR neurons. TRPC4/6-IR was expressed in only a small population of myenteric neurons, but was abundantly expressed in the submucosal plexus. TRPC4/6-IR was coexpressed with both cholinergic and nitrergic neurochemical codes in the myenteric plexus. In the submucosal plexus, TRPC4/6-IR was expressed exclusively in noncholinergic secretomotor neurons. No TRPC1/3/4/6-IR was found in calbindin-IR neurons. TRPC3/4/6-IR was widely expressed along varicose nerve fibers and colocalized with synaptophysin-IR at putative neurotransmitter release sites. Our results suggest important roles for TRPC channels in ENS physiology and neuronal regulation of gut function. PMID:18925632

Liu, Sumei; Qu, Mei-Hua; Ren, Wei; Hu, Hong-Zhen; Gao, Na; Wang, Guo-Du; Wang, Xi-Yu; Fei, Guijun; Zuo, Fei; Xia, Yun; Wood, Jackie D

2008-12-20

224

Uncertainty assessment of spatially distributed nitrate reduction potential in groundwater using multiple geological realizations  

NASA Astrophysics Data System (ADS)

Spatially distributed nitrate reduction potential in groundwater was estimated for the clay till dominated Norsminde fjord catchment in Denmark using the distributed hydrological model MIKE SHE. The nitrate transport was simulated using particle tracking and nitrate was assumed to be instantaneously reduced at the redox interface. Spatially distributed depths of the redox interface were estimated based on the spatial patterns in groundwater recharge and sediment redox capacity. Uncertainty of the estimated nitrate reduction due to geological uncertainty was assessed using multiple geological realizations. The geological realizations were generated using the geostatistical software TProGS and either conditioned based on borehole data only or soft conditioned based on both borehole data and geophysical data. Finally an upscaling of the predicted nitrate reduction was done in order to evaluate the change in uncertainty with increasing scale. The study showed that the uncertainty (one standard deviation) of the estimated nitrate reduction potential (in percentage of nitrate input) on the original 100 m model scale was 25% if only using borehole data and 19% if combining the borehole data with geophysical data. The uncertainty on the model predictions decreased with increasing aggregation scale. The decrease in uncertainty was most apparent the first 500 m, where after the uncertainty started to level off. This scale corresponded well to the mean length of the sand units within the clay till. It is concluded that using geophysical data in combination with borehole data in generation of geological realizations can help decrease uncertainty on the estimated nitrate reduction and that the predictive capability of distributed models is constrained by the spatial resolution of key data such as geology.

Hansen, A. L.; Gunderman, D.; He, X.; Refsgaard, J. C.

2014-11-01

225

Phenotypic identification of subclones in multiple myeloma with different chemoresistant, cytogenetic and clonogenic potential.  

PubMed

Knowledge about clonal diversity and selection is critical to understand multiple myeloma (MM) pathogenesis, chemoresistance and progression. If targeted therapy becomes reality, identification and monitoring of intraclonal plasma cell (PC) heterogeneity would become increasingly demanded. Here we investigated the kinetics of intraclonal heterogeneity among 116 MM patients using 23-marker multidimensional flow cytometry (MFC) and principal component analysis, at diagnosis and during minimal residual disease (MRD) monitoring. Distinct phenotypic subclones were observed in 35/116 (30%) newly diagnosed MM patients. In 10/35 patients, persistent MRD was detected after 9 induction cycles, and longitudinal comparison of patient-paired diagnostic vs MRD samples unraveled phenotypic clonal tiding after therapy in half (5/10) of the patients. After demonstrating selection of distinct phenotypic subsets by therapeutic pressure, we investigated whether distinct fluorescence-activated cell-sorted PC subclones had different clonogenic and cytogenetic profiles. In half (5/10) of the patients analyzed, distinct phenotypic subclones showed different clonogenic potential when co-cultured with stromal cells, and in 6/11 cases distinct phenotypic subclones displayed unique cytogenetic profiles by interphase fluorescence in situ hybridization, including selective del(17p13). Collectively, we unravel potential therapeutic selection of preexisting diagnostic phenotypic subclones during MRD monitoring; because phenotypically distinct PCs may show different clonogenic and cytogenetic profiles, identification and follow-up of unique phenotypic-genetic myeloma PC subclones may become relevant for tailored therapy.Leukemia advance online publication, 5 December 2014; doi:10.1038/leu.2014.321. PMID:25388955

Paíno, T; Paiva, B; Sayagués, J M; Mota, I; Carvalheiro, T; Corchete, L A; Aires-Mejía, I; Pérez, J J; Sanchez, M L; Barcena, P; Ocio, E M; San-Segundo, L; Sarasquete, M E; García-Sanz, R; Vidriales, M-B; Oriol, A; Hernández, M-T; Echeveste, M-A; Paiva, A; Blade, J; Lahuerta, J-J; Orfao, A; Mateos, M-V; Gutiérrez, N C; San-Miguel, J F

2014-11-12

226

Calculations of the K$^{+}$-Nucleus Microscopic Optical Potential and of the Corresponding Differential Elastic Cross Sections  

E-print Network

Calculations are made of the $K^{+}+^{12}$C, $^{40}$Ca differential elastic scattering cross sections at the beam momenta 0.635, 0.715, and 0.8 GeV/c. To this end the microscopic optical potential derived in the high-energy approximation was used where existing data on the kaon-nucleon amplitude and on the point-like density distributions of target-nuclei were utilized. The effect of different methods of relativization was studied and shown to play an important role. A good agreement with the experimental data on differential elastic cross sections was obtained.

V. K. Lukyanov; E. V. Zemlyanaya; K. V. Lukyanov; K. M. Hanna

2009-01-16

227

Assessment of visual and auditory evoked potentials in multiple sclerosis patients with and without fatigue.  

PubMed

The aim of the study was to evaluate visual and brainstem auditory evoked potentials (VEP, BAEP) in multiple sclerosis (MS) patients with regards to fatigue and disease-related variables. The study comprised 86 MS patients and 40 controls. Fatigue was assessed using the Fatigue Severity Scale (FSS/FSS-5) and the Modified Fatigue Impact Scale (MFIS). Latencies and amplitudes of the P100 component of VEP and the I-V components of BAEP were analyzed. The results of EP were compared between non-fatigued, moderately and severely fatigued MS patients and controls. P100 latency was increased and amplitude decreased in moderately and severely fatigued MS subjects. The latency of the V component of BAEP and interlatencies I-III-V were increased in severely fatigued patients. The amplitude of the V component was lowered in fatigued patients. VEP and BAEP abnormalities were usually one-sided. Interocular P100 latency difference tended to correlate with FSS/FSS-5. The parameters of VEP and BAEP correlated with functional system scores but not with MS duration, overall degree of disability or its progression over time. Significant, usually asymmetrical VEP and BAEP abnormalities were found in fatigued MS patients, with no relationships to disease-related variables. EP may be considered an electrophysiological marker of fatigue in MS patients. PMID:25240278

Pokryszko-Dragan, Anna; Bilinska, Malgorzata; Gruszka, Ewa; Kusinska, El?bieta; Podemski, Ryszard

2015-02-01

228

NICE technology appraisals: working with multiple levels of uncertainty and the potential for bias.  

PubMed

One of the key roles of the English National Institute for Health and Clinical Excellence (NICE) is technology appraisal. This essentially involves evaluating the cost effectiveness of pharmaceutical products and other technologies for use within the National Health Service. Based on a content analysis of key documents which shed light on the nature of appraisals, this paper draws attention to the multiple layers of uncertainty and complexity which are latent within the appraisal process, and the often socially constructed mechanisms for tackling these. Epistemic assumptions, bounded rationality and more explicitly relational forms of managing knowledge are applied to this end. These findings are discussed in the context of the literature highlighting the inherently social process of regulation. A framework is developed which posits the various forms of uncertainty, and responses to these, as potential conduits of regulatory bias-in need of further research. That NICE's authority is itself regulated by other actors within the regulatory regime, particularly the pharmaceutical industry, exposes it to the threat of regulatory capture. Following Lehoux, it is concluded that a more transparent and reflexive format for technological appraisals is necessary. This would enable a more robust, defensible form of decision-making and moreover enable NICE to preserve its legitimacy in the midst of pressures which threaten this. PMID:22198480

Brown, Patrick; Calnan, Michael

2013-05-01

229

Circulating endothelial progenitor cells as potential prognostic biomarker in multiple myeloma.  

PubMed

Recent studies suggest that endothelial progenitor cells (EPCs) are mobilized from bone marrow to the peripheral circulation and aid in tumor neovascularization. In this study, circulating EPC (cEPC) numbers were assessed and correlation with clinical and laboratory parameters was determined in 75 patients with multiple myeloma (MM). Higher numbers of cEPCs (defined as CD45-/dim CD34+CD133+CD31+cells) were observed in MM as compared to healthy controls (n = 10; p < 0.001), which increased progressively from stage I to stage III (p < 0.001). A significant decline in cEPC numbers after therapy was observed in patients who attained at least a partial response (n = 47; p < 0.001). cEPCs correlated with response duration, at a baseline cut-off value of 19.6 cEPCs/?L (p = 0.006) and 6.5 cEPCs/?L after therapy (p < 0.001). This study suggests that cEPC numbers and changes in their levels may serve as a potential biomarker of disease severity, response to therapy and treatment outcome in MM. PMID:21973309

Bhaskar, Archana; Gupta, Ritu; Kumar, Lalit; Sharma, Atul; Sharma, Mehar Chand; Kalaivani, Mani; Thakur, Sonu Chand

2012-04-01

230

Oscillatory Protein Expression Dynamics Endows Stem Cells with Robust Differentiation Potential  

PubMed Central

The lack of understanding of stem cell differentiation and proliferation is a fundamental problem in developmental biology. Although gene regulatory networks (GRNs) for stem cell differentiation have been partially identified, the nature of differentiation dynamics and their regulation leading to robust development remain unclear. Herein, using a dynamical system modeling cell approach, we performed simulations of the developmental process using all possible GRNs with a few genes, and screened GRNs that could generate cell type diversity through cell-cell interactions. We found that model stem cells that both proliferated and differentiated always exhibited oscillatory expression dynamics, and the differentiation frequency of such stem cells was regulated, resulting in a robust number distribution. Moreover, we uncovered the common regulatory motifs for stem cell differentiation, in which a combination of regulatory motifs that generated oscillatory expression dynamics and stabilized distinct cellular states played an essential role. These findings may explain the recently observed heterogeneity and dynamic equilibrium in cellular states of stem cells, and can be used to predict regulatory networks responsible for differentiation in stem cell systems. PMID:22073296

Kaneko, Kunihiko

2011-01-01

231

The utility of susceptibility-weighted imaging for differentiating Parkinsonism-predominant multiple system atrophy from Parkinson's disease: correlation with 18F-flurodeoxyglucose positron-emission tomography.  

PubMed

Our study was intended to demonstrate the different signal intensity (SI) pattern of the putamen seen on susceptibility-weighted imaging (SWI) between that of Parkinson's disease (PD) and Parkinsonism-predominant multiple system atrophy (MSA-P), and to correlate it with (18)F-flurodeoxyglucose positron-emission tomography ((18)F-FDG PET). Thirty patients with PD and 17 with MSA-P underwent SWI, and (18)F-FDG PET were included. The SI was measured on SWI in the anterior and posterior halves of the putamen using a region-of-interest (ROI) on both sides. The normalized regional glucose metabolism (standardized uptake value ratio, SUVR) was measured on co-registered (18)F-FDG PET images using the ROI obtained with SWI. Analysis included a group-level comparison of the SI values obtained on SWI, and these results were correlated with the SUVR on (18)F-FDG PET. The SIs of the bilateral posterior, dominant-side of the posterior, mean values of the bilateral anterior and posterior halves of the putamen on SWI, differed significantly between the two groups (P < 0.001, respectively). The SUVR of the all locations also differed significantly between PD and MSA-P (P < 0.001, respectively). There was a moderate degree of positive correlation between the SI and the SUVR of the left posterior half, and mean value of the bilateral posterior putamen in MSA-P (r = 0.634, P = 0.006, r = 0.492, P = 0.045). In conclusion, the low SI seen on the posterior putamen may differentiate MSA-P from PD. Furthermore, low SI in the putamen correlated with hypometabolism on (18)F-FDG PET. Therefore, SWI could be a potential complementary diagnostic tool to (18)F-FDG PET for differentiating these conditions. PMID:25450142

Yoon, Ra Gyoung; Kim, Sang Joon; Kim, Ho Sung; Choi, Choong Gon; Kim, Jae Seung; Oh, Jungsu; Chung, Sun J; Lee, Chong Sik

2015-01-01

232

SITE-SPECIFIC PHOSPHORYLATION OF CXCR4 IS DYNAMICALLY REGULATED BY MULTIPLE KINASES AND RESULTS IN DIFFERENTIAL MODULATION OF CXCR4  

E-print Network

1 SITE-SPECIFIC PHOSPHORYLATION OF CXCR4 IS DYNAMICALLY REGULATED BY MULTIPLE KINASES AND RESULTS IN DIFFERENTIAL MODULATION OF CXCR4 SIGNALING John M. Busillo1 , Sylvain Armando2 , Rajarshi Sengupta3 , Olimpia head: CXCR4 phosphorylation and regulation Address correspondence to: Jeffrey L. Benovic, Dept

Meucci, Olimpia

233

Multiple-Locus Variable-Number Tandem-Repeat Analysis Is a Suitable Tool for Differentiation of Mycoplasma hyopneumoniae Strains without Cultivation?  

PubMed Central

An assay based on multiple-locus variable-number tandem-repeat analysis allowed differentiating and studying diversity and persistence of Mycoplasma hyopneumoniae strains in pig herds without prior cultivation. The test had a discriminatory index of >0.99 and was applied reliably to porcine bronchoalveolar lavage fluid and tracheal swabs. PMID:21389157

Vranckx, K.; Maes, D.; Calus, D.; Villarreal, I.; Pasmans, F.; Haesebrouck, F.

2011-01-01

234

Multipotential differentiation of human urine-derived stem cells: potential for therapeutic applications in urology.  

PubMed

We sought to biologically characterize and identify a subpopulation of urine-derived stem cells (USCs) with the capacity for multipotent differentiation. We demonstrated that single USCs can expand to a large population with 60-70 population doublings. Nine of 15 individual USC clones expressed detectable levels of telomerase and have long telomeres. These cells expressed pericyte and mesenchymal stem cell markers. Upon induction with appropriate media in vitro, USCs differentiated into bladder-associated cell types, including functional urothelial and smooth muscle cell lineages. When the differentiated USCs were seeded onto a scaffold and subcutaneously implanted into nude mice, multilayered tissue-like structures formed consisting of urothelium and smooth muscle. Additionally, USCs were able to differentiate into endothelial, osteogenic, chondrogenic, adipogenic, skeletal myogenic, and neurogenic lineages but did not form teratomas during the 1-month study despite telomerase activity. USCs may be useful in cell-based therapies and tissue engineering applications, including urogenital reconstruction. PMID:23666768

Bharadwaj, Shantaram; Liu, Guihua; Shi, Yingai; Wu, Rongpei; Yang, Bin; He, Tongchuan; Fan, Yuxin; Lu, Xinyan; Zhou, Xiaobo; Liu, Hong; Atala, Anthony; Rohozinski, Jan; Zhang, Yuanyuan

2013-09-01

235

A novel differential diagnostic model based on multiple biological parameters for immunoglobulin A nephropathy  

PubMed Central

Background Immunoglobulin A nephropathy (IgAN) is the most common form of glomerulonephritis in China. An accurate diagnosis of IgAN is dependent on renal biopsies, and there is lack of non-invasive and practical classification methods for discriminating IgAN from other primary kidney diseases. The objective of this study was to develop a classification model for the auxiliary diagnosis of IgAN using multiparameter analysis with various biological parameters. Methods To establish an optimal classification model, 121 cases (58 IgAN vs. 63 non-IgAN) were recruited and statistically analyzed. The model was then validated in another 180 cases. Results Of the 57 biological parameters, there were 16 parameters that were significantly different (P?potential clinical applications in distinguishing IgAN from other primary kidney diseases. PMID:22738421

2012-01-01

236

Changes in the Potential Multiple Cropping System in Response to Climate Change in China from 1960–2010  

PubMed Central

The multiple cropping practice is essential to agriculture because it has been shown to significantly increase the grain yield and promote agricultural economic development. In this study, potential multiple cropping systems in China are calculated based on meteorological observation data by using the Agricultural Ecology Zone (AEZ) model. Following this, the changes in the potential cropping systems in response to climate change between the 1960s and the 2010s were subsequently analyzed. The results indicate that the changes of potential multiple cropping systems show tremendous heterogeneity in respect to the spatial pattern in China. A key finding is that the magnitude of change of the potential cropping systems showed a pattern of increase both from northern China to southern China and from western China to eastern China. Furthermore, the area found to be suitable only for single cropping decreased, while the area suitable for triple cropping increased significantly from the 1960s to the 2000s. During the studied period, the potential multiple cropping index (PMCI) gap between rain-fed and irrigated scenarios increased from 18% to 24%, which indicated noticeable growth of water supply limitations under the rain-fed scenario. The most significant finding of this research was that from the 1960s to the 2000s climate change had led to a significant increase of PMCI by 13% under irrigated scenario and 7% under rain-fed scenario across the whole of China. Furthermore, the growth of the annual mean temperature is identified as the main reason underlying the increase of PMCI. It has also been noticed that across China the changes of potential multiple cropping systems under climate change were different from region to region. PMID:24312511

Liu, Luo; Xu, Xinliang; Zhuang, Dafang; Chen, Xi; Li, Shuang

2013-01-01

237

Cellular network entropy as the energy potential in Waddington's differentiation landscape  

NASA Astrophysics Data System (ADS)

Differentiation is a key cellular process in normal tissue development that is significantly altered in cancer. Although molecular signatures characterising pluripotency and multipotency exist, there is, as yet, no single quantitative mark of a cellular sample's position in the global differentiation hierarchy. Here we adopt a systems view and consider the sample's network entropy, a measure of signaling pathway promiscuity, computable from a sample's genome-wide expression profile. We demonstrate that network entropy provides a quantitative, in-silico, readout of the average undifferentiated state of the profiled cells, recapitulating the known hierarchy of pluripotent, multipotent and differentiated cell types. Network entropy further exhibits dynamic changes in time course differentiation data, and in line with a sample's differentiation stage. In disease, network entropy predicts a higher level of cellular plasticity in cancer stem cell populations compared to ordinary cancer cells. Importantly, network entropy also allows identification of key differentiation pathways. Our results are consistent with the view that pluripotency is a statistical property defined at the cellular population level, correlating with intra-sample heterogeneity, and driven by the degree of signaling promiscuity in cells. In summary, network entropy provides a quantitative measure of a cell's undifferentiated state, defining its elevation in Waddington's landscape.

Banerji, Christopher R. S.; Miranda-Saavedra, Diego; Severini, Simone; Widschwendter, Martin; Enver, Tariq; Zhou, Joseph X.; Teschendorff, Andrew E.

2013-10-01

238

Gait analysis at multiple speeds reveals differential functional and structural outcomes in response to graded spinal cord injury.  

PubMed

Open-field behavioral scoring is widely used to assess spinal cord injury (SCI) outcomes, but has limited usefulness in describing subtle changes important for posture and locomotion. Additional quantitative methods are needed to increase the resolution of locomotor outcome assessment. This study used gait analysis at multiple speeds (GAMS) across a range of mild-to-severe intensities of thoracic SCI in the rat. Overall, Basso, Beattie, and Bresnahan (BBB) scores and subscores were assessed, and detailed automated gait analysis was performed at three fixed walking speeds (3.5, 6.0, and 8.5?cm/sec). Variability in hindpaw brake, propel, and stance times were analyzed further by integrating across the stance phase of stepping cycles. Myelin staining of spinal cord sections was used to quantify white matter loss at the injury site. Varied SCI intensity produced graded deficits in BBB score, BBB subscores, and spinal cord white matter and total volume loss. GAMS measures of posture revealed decreased paw area, increased limb extension, altered stance width, and decreased values for integrated brake, propel, and stance. Measures of coordination revealed increased stride frequency concomitant with decreased stride length, resulting in deviation from consistent forelimb/hindlimb coordination. Alterations in posture and coordination were correlated to impact severity. GAMS results correlated highly with functional and histological measures and revealed differential relationships between sets of GAMS dynamics and cord total volume loss versus epicenter myelin loss. Automated gait analysis at multiple speeds is therefore a useful tool for quantifying nuanced changes in gait as an extension of histological and observational methods in assessing SCI outcomes. PMID:24405378

Krizsan-Agbas, Dora; Winter, Michelle K; Eggimann, Linda S; Meriwether, Judith; Berman, Nancy E; Smith, Peter G; McCarson, Kenneth E

2014-05-01

239

Post-exercise facilitation and depression of motor evoked potentials to transcranial magnetic stimulation: a study in multiple sclerosis  

Microsoft Academic Search

Objective: To evaluate motor cortex excitability changes by transcranial magnetic stimulation (TMS) following repetitive muscle contractions in patients with multiple sclerosis (MS); to state whether a typical pattern of post-exercise motor evoked potentials (MEPs) is related to clinical fatigue in MS.Methods: In 41 patients with definite MS (32 with fatigue and 9 without fatigue according to Fatigue Severity Scale) and

A Perretti; P Balbi; G Orefice; L Trojano; L Marcantonio; V Brescia-Morra; S Ascione; F Manganelli; G Conte; L Santoro

2004-01-01

240

PTSD and Comorbid Disorders in a Representative Sample of Adolescents: The Risk Associated with Multiple Exposures to Potentially Traumatic Events  

ERIC Educational Resources Information Center

Objective: This study compared the impact of multiple exposures to potentially traumatic events (PTEs), including sexual victimization, physical victimization, and witnessed violence, on posttraumatic stress disorder (PTSD) and comorbid conditions (i.e., major depressive episode [MDE], and substance use [SUD]). Methods: Participants were a…

Macdonald, Alexandra; Danielson, Carla Kmett; Resnick, Heidi S.; Saunders, Benjamin E.; Kilpatrick, Dean G.

2010-01-01

241

Student Interactions with CD-ROM Storybooks: A Look at Potential Relationships between Multiple Intelligence Strengths and Levels of Interaction  

ERIC Educational Resources Information Center

This study looked at the potential relationship that may exist between students' intelligence strengths, in particular their spatial and kinesthetic strengths, and their combined cognitive and metacognitive levels of interaction with a CD-ROM storybook. The multiple intelligence strengths of a sample of students, measured via the MIDAS/My…

Huffman, Celia A.

2012-01-01

242

Differentiation potentials of perivascular cells in the bone tissue remodeling zones under microgravity  

NASA Astrophysics Data System (ADS)

Adaptive remodeling processes in the skeleton bones occur in the close topographical interconnection with blood capillaries followed by perivascular cells. Radioautographic studies with 3?- thymidine (Kimmel D.B., Fee W.S., 1980; Rodionova N.V., 1989, 2006) has shown that in osteogenesis zones there is sequential differentiation process of the perivascular cells into osteogenic ones. Using electron microscopy and cytochemistry we studied perivsacular cells in metaphysis of the rats femoral bones under conditions of modeling microgravity (28 days duration) and in femoral bon?s metaphyses of rats flown on board of the space laboratory (Spacelab - 2) It was revealed that population of the perivascular cells is not homogeneous in adaptive zones of the remodeling in both control and test groups (lowering support loading). This population comprises adjacent to endothelium little differentiated forms and isolated cells with differentiation features (specific volume of rough endoplasmic reticulum in cytoplasm is increased). Majority of the perivascular cells in the control group reveals reaction to alkaline phosphatase (marker of the osteogenic differentiation). In little differentiated cells this reaction is registered in nucleolus, nucleous and cytoplasm. In differentiating cells activity of the alkaline phosphatase is also detected on the outer surface of the cellular membrane. Unlike the control group in the bones of animals under microgravitaty reaction to the alkaline phosphatase is registered not for all cells of perivascular population. Part of the differentiating perivascular cells does not contain a product of the reaction. There is also visible trend of individual alkaline phosphatase containing perivascular cells amounts decrease (i.e. osteogenic cells-precursors). Under microgravity some little differentiated perivascular cells reveal destruction signs. Found decrease trend of the alkaline phosphatase containing cells (i.e. osteogenic cells) number in perivascular cells population. It is one of the mechanisms of the osteogenic process intensity decrease in bones due to lowering support loading on the bone skeleton. In particular this is confirmed by the fact that in the zones of adaptive remodeling we found fibroblasts and fibrosis zones - areas filled with non mineralized collagen fibrils on the bones surfaces. Hence it should be considered that lowering (removal) support loading slows down (or blocks) osteogenic differentiation of the perivascular cells part and stimulates differentiation of the fibroblast cells. Obtained data considered as one of the cellular mechanisms of the adaptive reactions development in spongy bone under microgravity which could lead to the bone mass loss.

Rodionova, Natalia; Katkova, Olena

243

Identification of genes associated with the differentiation potential of adipose-derived stem cells to osteocytes or myocytes.  

PubMed

Adipose-derived stem cells (ADSCs) have been considered as the optimal cells for regenerative medicine because ADSCs have the potential of multi-directional differentiation. To study the mechanisms of ADSCs differentiation, we analyzed microarray of GSE37329. GSE37329 was downloaded from Gene Expression Omnibus including 3 ADSCs, 2 ADSCs-derived osteocytes, and 2 ADSCs-derived myocytes samples. The differentially expressed genes (DEGs) were screened using limma package. Their underlying functions were predicted by gene ontology and pathway enrichment analyses. Besides, the interaction relationships of the proteins encoded by DEGs were obtained from STRING database, and protein-protein interaction (PPI) network was constructed using Cytoscape. Furthermore, modules analysis of PPI network was performed using MCODE in Cytoscape. We screened 662 and 484 DEG separately for the ADSCs-derived osteocytes and myocytes compared with ADSCs. There were 205 common up-regulated and 128 common down-regulated DEGs between the two groups. Function enrichment indicated that these common DEGs, especially, VEGFA, FGF2, and EGR1 may be related to cell differentiation. PPI network for common DEGs also suggested that VEGFA (degree = 29), FGF2 (degree = 17), and EGR1 (degree = 12) might be more important because they had higher connectivity degrees, and they might be involved in cell differentiation by interacting with other genes in module A (e.g., EGR1-NGF and EGR1-LEP), and B (e.g., VEGFA-PDGFD). Additionally, the IGF1 and BTG1 may be, respectively, specific for osteocytes and myocytes differentiation. VEGFA, PDGFD, FGF2, EGR1, NGF, LEP, IGF1, and BTG1 might serve as target genes in regulating ADSCs differentiation. PMID:25385480

Ren, Yizhong; Han, Changxu; Wang, Jingjuan; Jia, Yanbo; Kong, Lingyue; Eerdun, Tu; Wu, Lishuan; Jiang, Dianming

2015-02-01

244

Stereotactic Ablative Radiotherapy: A Potentially Curable Approach to Early-Stage Multiple Primary Lung Cancer  

PubMed Central

BACKGROUND Surgical resection has been the standard treatment for early-stage multiple primary lung cancer (MPLC). However, a significant proportion of patients with MPLC cannot undergo surgery. We explored here the role of stereotactic ablative radiotherapy (SABR) for patients with MPLC. METHODS We reviewed MPLC cases treated with SABR (50 Gy in 4 fractions or 70 Gy in 10 fractions) for the second tumor. Four-dimensional CT–based planning/volumetric image-guided treatment was used for all patients. Treatment outcomes/toxicities were analyzed. RESULTS For the 101 patients treated with SABR, at a median follow-up interval of 36 months and median overall survival of 46 months, 2-year and 4-year in-field local control rates were 97.4% and 95.7%. 2- and 4-year rates of overall survival (OS) were 73.2% and 47.5% and progression-free survival (PFS) were 67.0% and 58.0%. Patients with metachronous tumors had higher OS and PFS than did patients with synchronous tumors (2-year OS 80.6% metachronous vs. 61.5% synchronous; 4-year OS 52.7% vs. 39.7%; p=0.047; 2-year PFS 84.7% vs. 49.4%; 4-year PFS 75.6% vs. 30.4%; p=0.0001). For patients whose index tumor was treated with surgery or SABR, the incidence of grade ?3 radiation pneumonitis was 3% (2/71), but this increased to 17% (5/30) for patients whose index tumor was treated with conventional radiotherapy. Other grade ?3 toxicities included grade 3 chest wall pain (3/101, 3%) and grade 3 skin toxicity (1/101, 1%). CONCLUSIONS SABR achieves promising long- term tumor control, survival and could be a potential curative treatment of early-stage MPLC. PMID:23798353

Chang, Joe Y.; Liu, Yung-Hsien; Zhu, Zhengfei; Welsh, James W.; Gomez, Daniel R.; Komaki, Ritsuko; Roth, Jack A.; Swisher, Stephen G.

2013-01-01

245

Interleukin-1? promotes long-term potentiation in patients with multiple sclerosis.  

PubMed

The immune system shapes synaptic transmission and plasticity in experimental autoimmune encephalomyelitis (EAE), the mouse model of multiple sclerosis (MS). These synaptic adaptations are believed to drive recovery of function after brain lesions, and also learning and memory deficits and excitotoxic neurodegeneration; whether inflammation influences synaptic plasticity in MS patients is less clear. In a cohort of 59 patients with MS, we found that continuous theta-burst transcranial magnetic stimulation did not induce the expected long-term depression (LTD)-like synaptic phenomenon, but caused persisting enhancement of brain cortical excitability. The amplitude of this long-term potentiation (LTP)-like synaptic phenomenon correlated with the concentration of the pro-inflammatory cytokine interleukin-1? (IL-1?) in the cerebrospinal fluid. In MS and EAE, the brain and spinal cord are typically enriched of CD3(+) T lymphocyte infiltrates, which are, along with activated microglia and astroglia, a major cause of inflammation. Here, we found a correlation between the presence of infiltrating T lymphocytes in the hippocampus of EAE mice and synaptic plasticity alterations. We observed that T lymphocytes from EAE, but not from control mice, release IL-1? and promote LTP appearance over LTD, thereby mimicking the facilitated LTP induction observed in the cortex of MS patients. EAE-specific T lymphocytes were able to suppress GABAergic transmission in an IL-1?-dependent manner, providing a possible synaptic mechanism able to lower the threshold of LTP induction in MS brains. Moreover, in vivo blockade of IL-1? signaling resulted in inflammation and synaptopathy recovery in EAE hippocampus. These data provide novel insights into the pathophysiology of MS. PMID:23892937

Mori, Francesco; Nisticò, Robert; Mandolesi, Georgia; Piccinin, Sonia; Mango, Dalila; Kusayanagi, Hajime; Berretta, Nicola; Bergami, Alessandra; Gentile, Antonietta; Musella, Alessandra; Nicoletti, Carolina G; Nicoletti, Ferdinando; Buttari, Fabio; Mercuri, Nicola B; Martino, Gianvito; Furlan, Roberto; Centonze, Diego

2014-03-01

246

"So Much Potential in Reading!" Developing Meaningful Literacy Routines for Students with Multiple Disabilities  

ERIC Educational Resources Information Center

Children with multiple disabilities, often experience challenges in communication, mobility, and learning. Despite these challenges, substantial research exists that documents successful educational methods and strategies for these students. Specifically, students with multiple disabilities have successfully been taught to use a voice output…

Fenlon, Amanda G.; McNabb, Jessica; Pidlypchak, Harmony

2010-01-01

247

Astaxanthin improves the proliferative capacity as well as the osteogenic and adipogenic differentiation potential in neural stem cells  

Microsoft Academic Search

In the present study, the effect of astaxanthin on improvement of the proliferative capacity as well as the osteogenic and adipogenic differentiation potential in neural stem cells (NSCs) was evaluated. Treatment of astaxanthin-induced actives cell growth in a dose-dependent and time-dependent manner. Results from a clonogenic assay clearly indicated that astaxanthin can actively stimulate proliferation of NSCs. Astaxanthin-induced improvement in

Jeong Hwan Kim; Soo-Wan Nam; Byung Woo Kim; Wun-Jae Kim; Yung Hyun Choi

2010-01-01

248

The Effect of the Residual Ion Potential on the Fully Differential Cross Section of Helium for Ionization by Electron Impact  

SciTech Connect

We have carried out calculations for the fully differential cross section of the ionization of helium by electron projectiles. In order to study the effect of the residual ion potential, we employed three models, and tested them for the coplanar and perpendicular plane geometry. In spite of the simplicity of our models, the results for the coplanar case are in fair agreement with the available experimental data. The results for the perpendicular geometry need more improvement.

Toth, A.; Nagy, L. [Faculty of Physics, Babes-Bolyai University, str. Kogalniceanu nr.1, 400084 Cluj (Romania)

2011-10-03

249

Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke  

PubMed Central

Aims Cerebral small vessel disease (SVD) causes a fifth of all strokes plus diffuse brain damage leading to cognitive decline, physical disabilities and dementia. The aetiology and pathogenesis of SVD are unknown, but largely attributed to hypertension or microatheroma. Methods We used the spontaneously hypertensive stroke-prone rat (SHRSP), the closest spontaneous experimental model of human SVD, and age-matched control rats kept under identical, non-salt-loaded conditions, to perform a blinded analysis of mRNA microarray, qRT-PCR and pathway analysis in two brain regions (frontal and mid-coronal) commonly affected by SVD in the SHRSP at age five, 16 and 21 weeks. Results We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats. All were present at age 5 weeks thus predating blood pressure elevation. ‘Neurological’ and ‘inflammatory’ pathways were more affected than ‘vascular’ functional pathways. Conclusions This set of defects, although individually modest, when acting in combination could explain the SHRSP's susceptibility to microvascular and brain injury, compared with control rats. Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD. PMID:24417612

Bailey, Emma L; McBride, Martin W; Beattie, Wendy; McClure, John D; Graham, Delyth; Dominiczak, Anna F; Sudlow, Cathie LM; Smith, Colin; Wardlaw, Joanna M

2014-01-01

250

Multiple, correlated covariates associated with differential item functioning (DIF): Accounting for language DIF when education levels differ across languages  

PubMed Central

Differential item functioning (DIF) occurs when a test item has different statistical properties in subgroups, controlling for the underlying ability measured by the test. DIF assessment is necessary when evaluating measurement bias in tests used across different language groups. However, other factors such as educational attainment can differ across language groups, and DIF due to these other factors may also exist. How to conduct DIF analyses in the presence of multiple, correlated factors remains largely unexplored. This study assessed DIF related to Spanish versus English language in a 44-item object naming test. Data come from a community-based sample of 1,755 Spanish- and English-speaking older adults. We compared simultaneous accounting, a new strategy for handling differences in educational attainment across language groups, with existing methods. Compared to other methods, simultaneously accounting for language- and education-related DIF yielded salient differences in some object naming scores, particularly for Spanish speakers with at least 9 years of education. Accounting for factors that vary across language groups can be important when assessing language DIF. The use of simultaneous accounting will be relevant to other cross-cultural studies in cognition and in other fields, including health-related quality of life. PMID:22900138

Gibbons, Laura E.; Crane, Paul K.; Mehta, Kala M.; Pedraza, Otto; Tang, Yuxiao; Manly, Jennifer J.; Narasimhalu, Kaavya; Teresi, Jeanne; Jones, Richard N.; Mungas, Dan

2012-01-01

251

MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction.  

PubMed

Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a -168A --> G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components. PMID:15821736

Swanberg, Maria; Lidman, Olle; Padyukov, Leonid; Eriksson, Per; Akesson, Eva; Jagodic, Maja; Lobell, Anna; Khademi, Mohsen; Börjesson, Ola; Lindgren, Cecilia M; Lundman, Pia; Brookes, Anthony J; Kere, Juha; Luthman, Holger; Alfredsson, Lars; Hillert, Jan; Klareskog, Lars; Hamsten, Anders; Piehl, Fredrik; Olsson, Tomas

2005-05-01

252

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci.  

PubMed

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21?856) and multiple sclerosis (MS) (n=43?879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16?731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility. PMID:24468824

Andreassen, O A; Harbo, H F; Wang, Y; Thompson, W K; Schork, A J; Mattingsdal, M; Zuber, V; Bettella, F; Ripke, S; Kelsoe, J R; Kendler, K S; O'Donovan, M C; Sklar, P; McEvoy, L K; Desikan, R S; Lie, B A; Djurovic, S; Dale, A M

2015-02-01

253

Genetic pleiotropy between multiple sclerosis and schizophrenia but not bipolar disorder: differential involvement of immune-related gene loci  

PubMed Central

Converging evidence implicates immune abnormalities in schizophrenia (SCZ), and recent genome-wide association studies (GWAS) have identified immune-related single-nucleotide polymorphisms (SNPs) associated with SCZ. Using the conditional false discovery rate (FDR) approach, we evaluated pleiotropy in SNPs associated with SCZ (n=21?856) and multiple sclerosis (MS) (n=43?879), an inflammatory, demyelinating disease of the central nervous system. Because SCZ and bipolar disorder (BD) show substantial clinical and genetic overlap, we also investigated pleiotropy between BD (n=16?731) and MS. We found significant genetic overlap between SCZ and MS and identified 21 independent loci associated with SCZ, conditioned on association with MS. This enrichment was driven by the major histocompatibility complex (MHC). Importantly, we detected the involvement of the same human leukocyte antigen (HLA) alleles in both SCZ and MS, but with an opposite directionality of effect of associated HLA alleles (that is, MS risk alleles were associated with decreased SCZ risk). In contrast, we found no genetic overlap between BD and MS. Considered together, our findings demonstrate genetic pleiotropy between SCZ and MS and suggest that the MHC signals may differentiate SCZ from BD susceptibility. PMID:24468824

Andreassen, O A; Harbo, H F; Wang, Y; Thompson, W K; Schork, A J; Mattingsdal, M; Zuber, V; Bettella, F; Ripke, S; Kelsoe, J R; Kendler, K S; O'Donovan, M C; Sklar, P; McEvoy, L K; Desikan, R S; Lie, B A; Djurovic, S; Dale, A M

2015-01-01

254

The Multiple Endocrine Neoplasia Type 1 (MEN1) Tumor Suppressor Regulates Peroxisome Proliferator-Activated Receptor ?-Dependent Adipocyte Differentiation?  

PubMed Central

Menin, the product of the MEN1 (multiple endocrine neoplasia type 1) tumor suppressor gene, is involved in activation of gene transcription as part of an MLL1 (mixed-lineage leukemia 1)/MLL2 (KMT2A/B)-containing protein complex which harbors methyltransferase activity for lysine 4 of histone H3 (H3K4). As MEN1 patients frequently develop lipomas and peroxisome proliferator-activated receptor ? (PPAR?) is expressed in several MEN1-related tumor types, we investigated regulation of PPAR? activity by menin. We found that menin is required for adipocyte differentiation of murine 3T3-L1 cells and PPAR?-expressing mouse embryonic fibroblasts. Menin augments PPAR? target gene expression through recruitment of H3K4 methyltransferase activity. Menin interacts directly with the activation function 2 transcription activation domain of PPAR? in a ligand-independent fashion. Ligand-dependent coactivation, however, is dependent on the LXXLL motif of menin and the intact helix 12 of PPAR?. We propose that menin is an important factor in PPAR?-mediated adipogenesis and that loss of PPAR? function may contribute to lipoma development in MEN1 patients. PMID:19596783

Dreijerink, Koen M. A.; Varier, Radhika A.; van Beekum, Olivier; Jeninga, Ellen H.; Höppener, Jo W. M.; Lips, Cornelis J. M.; Kummer, J. Alain; Kalkhoven, Eric; Timmers, H. T. Marc

2009-01-01

255

Friend of GATA (FOG)-1 and FOG-2 differentially repress the GATA-dependent activity of multiple gonadal promoters.  

PubMed

The GATA transcription factors are crucial regulators of cell-specific gene expression in many tissues. GATA proteins are abundantly expressed in gonads of several species. In vertebrates, GATA factors are expressed from the onset of gonadal development and are later found in multiple cell lineages of both the testis and ovary. GATA factors activate transcription of several gonadal genes including the hormone-encoding genes Müllerian inhibiting substance (MIS) and inhibin alpha and genes involved in steroidogenesis like P450 aromatase (Cyp 19) and steroidogenic acute regulatory protein. GATA factors also contribute to cell-specific gonadal gene expression through cooperative interactions with other transcription factors such as the orphan nuclear receptor steroidogenic factor-1. GATA transcriptional activity is also modulated by two multitype zinc finger proteins called the Friend of GATA (FOG) proteins, which were cloned as GATA-specific cofactors. The FOG proteins (FOG-1 and FOG-2) can act as either enhancers or repressors of GATA transcriptional activity, depending on the cell and promoter context. We now report that the FOG proteins are coexpressed with GATA factors in testicular cells in which they differentially repress the promoter activities of several GATA-dependent target genes. These findings implicate the FOG proteins in the regulation of GATA-dependent gene transcription in the gonads. PMID:12239108

Robert, Nicholas M; Tremblay, Jacques J; Viger, Robert S

2002-10-01

256

Differentiation of Equine Mesenchymal Stromal Cells into Cells of Neural Lineage: Potential for Clinical Applications  

PubMed Central

Mesenchymal stromal cells (MSCs) are able to differentiate into extramesodermal lineages, including neurons. Positive outcomes were obtained after transplantation of neurally induced MSCs in laboratory animals after nerve injury, but this is unknown in horses. Our objectives were to test the ability of equine MSCs to differentiate into cells of neural lineage in vitro, to assess differences in morphology and lineage-specific protein expression, and to investigate if horse age and cell passage number affected the ability to achieve differentiation. Bone marrow-derived MSCs were obtained from young and adult horses. Following demonstration of stemness, MSCs were neurally induced and microscopically assessed at different time points. Results showed that commercially available nitrogen-coated tissue culture plates supported proliferation and differentiation. Morphological changes were immediate and all the cells displayed a neural crest-like cell phenotype. Expression of neural progenitor proteins, was assessed via western blot or immunofluorescence. In our study, MSCs generated from young and middle-aged horses did not show differences in their ability to undergo differentiation. The effect of cell passage number, however, is inconsistent and further experiments are needed. Ongoing work is aimed at transdifferentiating these cells into Schwann cells for transplantation into a peripheral nerve injury model in horses. PMID:25506367

Cruz Villagrán, Claudia; Amelse, Lisa; Neilsen, Nancy; Dunlap, John; Dhar, Madhu

2014-01-01

257

Roles of Potential Gradient and Electrode Bandwidth on Negative Differential Resistance in One-Dimensional Band Insulator  

NASA Astrophysics Data System (ADS)

A negative differential resistance (NDR) in a one-dimensional band insulator attached to electrodes is investigated. We systematically examine the effects of an electrode bandwidth and a potential distribution inside the insulator on current–voltage characteristics. We show that, in uncorrelated systems, the NDR is generally caused by a linear potential gradient as well as by a finite electrode bandwidth. In particular, the former reduces the effective bandwidth of the insulator for elastic tunneling by tilting its energy band, so that it brings about the NDR even in the limit of large electrode bandwidth.

Tanaka, Yasuhiro; Yonemitsu, Kenji

2014-12-01

258

TGF-?1 up-regulates connexin43 expression: A potential mechanism for human trophoblast cell differentiation.  

PubMed

Connexin43 (Cx43)-mediated gap junctional intercellular communication (GJIC) are required for human trophoblast differentiation. To date, whether Cx43 mediates TGF-?1-induced trophoblast differentiation has not been determined. We showed that treatment with TGF-?1 increased Cx43 expression and GJIC in HTR-8/SVneo human trophoblast cells. In addition, Smad and ERK1/2 signaling pathways were involved in TGF-?1-induced up-regulation of Cx43. Moreover, TGF-?1 increased the expression of the syncytiotrophoblast marker, ?-hCG. Importantly, knockdown of Cx43 abolished the TGF-?1-induced up-regulation of ?-hCG. Furthermore, overexpression of Cx43 up-regulated ?-hCG expression. These results provide evidence that Cx43 and GJIC activity are up-regulated by TGF-?1 in human trophoblast cells, which subsequently contributes to TGF-?1-induced trophoblast differentiation. J. Cell. Physiol. 230: 1558-1566, 2015. © 2015 Wiley Periodicals, Inc., A Wiley Company. PMID:25560303

Cheng, Jung-Chien; Chang, Hsun-Ming; Fang, Lanlan; Sun, Ying-Pu; Leung, Peter C K

2015-07-01

259

Evaluation of evoked potentials and lymphocyte subsets as possible markers of multiple sclerosis: one year follow up of 30 patients.  

PubMed Central

Evoked potentials and T-lymphocyte helper/suppressor ratio (H/S) were evaluated serially together with neurological status in 30 definite multiple sclerosis patients to evaluate their possible role in monitoring disease progression. Evoked potentials in many cases reflected the clinical status of the pathways tested, but some exceptions were observed, probably due to subclinical relapses or physical factors. In some instances the occurrence of subclinical relapses was suggested by increased H/S ratios. Serial H/S values increased in parallel with clinical and subclinical relapses, and seemed to show specific patterns in relation to the type of clinical course (relapsing, stable, chronic progressive). Our results suggest that evoked potentials and H/S ratio serial analysis can contribute to a better assessment of the progress of multiple sclerosis. PMID:3489075

Ghezzi, A; Zaffaroni, M; Caputo, D; Montanini, R; Cazzullo, C L

1986-01-01

260

Hypoxia increases Sca-1/CD44 co-expression in murine mesenchymal stem cells and enhances their adipogenic differentiation potential.  

PubMed

Mesenchymal stem cells (MSCs) are usually cultured under normoxic conditions (21% oxygen). However, in vivo, the physiological "niches" for MSCs have a much lower oxygen tension. Because of their plasticity, stem cells are particularly sensitive to their environments, and oxygen tension is one developmentally important stimulus in stem cell biology and plays a role in the intricate balance between cellular proliferation and commitment towards differentiation. Therefore, we investigated here the effect of hypoxia (2% oxygen) on murine adipose tissue (AT) MSC proliferation and adipogenic differentiation. AT cells were obtained from the omental fat and AT-MSCs were selected for their ability to attach to the plastic dishes, and were grown under normoxic and hypoxic conditions. Prior exposure of MSCs to hypoxia led to a significant reduction of ex vivo expansion time, with significantly increased numbers of Sca-1(+) as well as Sca-1(+)/CD44(+)double-positive cells. Under low oxygen culture conditions, the AT-MSC number markedly increased and their adipogenic differentiation potential was reduced. Notably, the hypoxia-mediated inhibition of adipogenic differentiation was reversible: AT-MSCs pre-exposed to hypoxia when switched to normoxic conditions exhibited significantly higher adipogenic differentiation capacity compared to their pre-exposed normoxic-cultured counterparts. Accordingly, the expression of adipocyte-specific genes, peroxisome proliferator activated receptor gamma (Ppargamma), lipoprotein lipase (Lpl) and fatty acid binding protein 4 (Fabp4) were significantly enhanced in hypoxia pre-exposed AT-MSCs. In conclusion, pre-culturing MSCs under hypoxic culture conditions may represent a strategy to enhance MSC production, enrichment and adipogenic differentiation. PMID:20496083

Valorani, M G; Germani, A; Otto, W R; Harper, L; Biddle, A; Khoo, C P; Lin, W R; Hawa, M I; Tropel, P; Patrizi, M P; Pozzilli, P; Alison, M R

2010-07-01

261

Neural differentiation potential of human bone marrow-derived mesenchymal stromal cells: misleading marker gene expression  

Microsoft Academic Search

BACKGROUND: In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing

Katrin Montzka; Nina Lassonczyk; Beate Tschöke; Sabine Neuss; Tobias Führmann; Rachelle Franzen; Ralf Smeets; Gary A Brook; Michael Wöltje

2009-01-01

262

Cardiac myofibroblast differentiation is attenuated by ? 3 integrin blockade: Potential role in post-MI remodeling  

Microsoft Academic Search

Cardiac fibroblasts and myofibroblasts are responsible for post-MI remodeling which occurs via regulation of extracellular matrix (ECM). Accelerated post-MI remodeling leads to excessive ECM deposition and fibrosis, contributing to impaired contractile function, arrhythmias, and heart failure. We have previously reported that type VI collagen induces myofibroblast differentiation in cultured cardiac fibroblasts, and that type VI collagen and myofibroblast content were

Jennifer E. Bryant; Patricia E. Shamhart; Daniel J. Luther; Erik R. Olson; John C. Koshy; Donald J. Costic; Monica V. Mohile; Michelle Dockry; Kathleen J. Doane; J. Gary Meszaros

2009-01-01

263

CYCLIC AMP, CYCLIC GMP, AND GLUCOCORTICOIDS AS POTENTIAL METABOLIC REGULATORS OF EPIDERMAL PROLIFERATION AND DIFFERENTIATION  

Microsoft Academic Search

The two cyclic nucleotides, cyclic AMP and cyclic GMP, appear to be central to the metabolic regulation of cell proliferation and differentiation in various cells. Moreover, in many systems glucocorticoids appear to act in concert with or parallel to cyclic AMP. The available evidence suggests that these three molecular species – cyclic AMP, cyclic GMP, and glucocorticoids – may be

John J. Voorhees; Cynthia L. Marcelo; Elizabeth A. Duell

1975-01-01

264

Potential immunological consequences of pharmacological suppression of gastric acid production in patients with multiple sclerosis  

E-print Network

Corticosteroids are standard treatment for patients with multiple sclerosis experiencing acute relapse. Because dyspeptic pain is a common side effect of this intervention, patients can be given a histamine receptor-2 antagonist, proton pump...

Biswas, Sangita; Benedict, Stephen H.; Lynch, Sharon G.; LeVine, Steven M.

2012-06-07

265

The efficacy and safety of daclizumab and its potential role in the treatment of multiple sclerosis  

PubMed Central

Daclizumab is a humanized monoclonal antibody of the immunoglobulin G1 (IgG1) isotype that binds to the ?-subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor expressed on activated T cells and CD4+CD25+FoxP3+ regulatory T cells. Based on the assumption that it would block the activation and expansion of autoreactive T cells that are central to the immune pathogenesis of multiple sclerosis (MS), daclizumab was tested in several small open-label clinical trials in MS and demonstrated a profound inhibition of inflammatory disease activity. Surprisingly, accompanying mechanistic studies revealed that the most important biological effect of daclizumab was rather a dramatic expansion and activation of immunoregulatory CD56bright natural-killer (NK) cells that correlated with treatment response, while there was no or only minor effect on peripheral T-cell activation and function. These CD56bright NK cells were able to gain access to the central nervous system in MS and kill autologous activated T cells. Additional and relatively large phase IIb clinical trials showed that daclizumab, as add-on or monotherapy in relapsing–remitting (RR) MS, was highly effective in reducing relapse rate, disability progression, and the number and volume of gadolinium-enhancing, T1 and T2 lesions on brain magnetic resonance imaging (MRI), and reproduced the expansion of CD56bright NK cells as a biomarker for daclizumab activity. Daclizumab is generally very well tolerated and has shown a favorable adverse event (AE) profile in transplant recipients. However, several potentially serious and newly emerging AEs (mainly infections, skin reactions, elevated liver function tests and autoimmune phenomena in several body organs) may require strict safety monitoring programs in future clinical practice and place daclizumab together with other new and highly effective MS drugs as a second-line therapy. Ongoing phase III clinical trials in RRMS are expected to provide definite information on the efficacy and safety of daclizumab and to determine its place in the fast-growing armamentarium of MS therapies. PMID:24409199

2014-01-01

266

Selection pressures have caused genome-wide population differentiation of Anthoxanthum odoratum despite the potential for high gene flow.  

PubMed

The extent to which divergent selection can drive genome-wide population differentiation remains unclear. Theory predicts that in the face of ongoing gene flow, population differentiation should be apparent only at those markers that are directly or indirectly (i.e. through linkage) under selection. However, if reproductive barriers limit gene flow, genome-wide population differentiation may occur even in geographically proximate populations. Some insight into the link between selection and genetic differentiation in the presence of ongoing gene flow can come from long-term experiments such as The Park Grass Experiment, which has been running for over 150 years, and provides a unique example of a heterogeneous environment with a long and detailed history. Fertilizer treatments applied in the Park Grass Experiment have led to rapid evolutionary change in sweet vernal grass Anthoxanthum odoratum, but until now, nothing was known of how these changes would be reflected in neutral molecular markers. We have genotyped ten A. odoratum populations from the Park Grass Experiment using Amplified Fragment Length Polymorphisms (AFLPs). Our data show that nutrient additions have resulted in genome-wide divergence among plots despite the high potential for ongoing gene flow. This provides a well-documented example of concordance between genomes and environmental conditions that has arisen in continuous populations across a time span of fewer than 75 generations. PMID:20163507

Freeland, J R; Biss, P; Conrad, K F; Silvertown, J

2010-04-01

267

Graphene supports in vitro proliferation and osteogenic differentiation of goat adult mesenchymal stem cells: potential for bone tissue engineering.  

PubMed

Current treatments for bone loss injuries involve autologous and allogenic bone grafts, metal alloys and ceramics. Although these therapies have proved useful, they suffer from inherent challenges, and hence, an adequate bone replacement therapy has not yet been found. We hypothesize that graphene may be a useful nanoscaffold for mesenchymal stem cells and will promote proliferation and differentiation into bone progenitor cells. In this study, we evaluate graphene, a biocompatible inert nanomaterial, for its effect on in vitro growth and differentiation of goat adult mesenchymal stem cells. Cell proliferation and differentiation are compared between polystyrene-coated tissue culture plates and graphene-coated plates. Graphitic materials are cytocompatible and support cell adhesion and proliferation. Importantly, cells seeded on to oxidized graphene films undergo osteogenic differentiation in fetal bovine serum-containing medium without the addition of any glucocorticoid or specific growth factors. These findings support graphene's potential to act as an osteoinducer and a vehicle to deliver mesenchymal stem cells, and suggest that the combination of graphene and goat mesenchymal stem cells provides a promising construct for bone tissue engineering. Copyright © 2014 John Wiley & Sons, Ltd. PMID:25220951

Elkhenany, Hoda; Amelse, Lisa; Lafont, Andersen; Bourdo, Shawn; Caldwell, Marc; Neilsen, Nancy; Dervishi, Enkeleda; Derek, Oshin; Biris, Alexandru S; Anderson, David; Dhar, Madhu

2015-04-01

268

Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells.  

PubMed

Age-associated changes of T and NK cell (T/NK) potential of human hematopoietic stem cells are unknown. In this study, we enumerate and characterize T/NK precursors among CD34(+)Lin(-) cell populations circulating in normal human adult peripheral blood (PB) by a limiting-dilution assay using coculture with OP9-DL1 stroma cells expressing Notch 1 ligand, Delta-like 1. The frequency of T cell precursors in CD34(+)Lin(-) cells was found to decrease with donor age, whereas the ratio of NK to T cell precursor frequency (NK/T ratio) increased with age, suggesting that lymphoid differentiation potential of PB progenitors shifts from T to NK cell lineage with aging. Clonal analyses of CD34(+)Lin(-) cells showed that differences in the NK/T ratio were attributable to different distributions of single- and dual-lineage T/NK precursor clones. Because nearly all of the clones retained monocyte and/or granulocyte differentiation potentials in coculture with OP9-DL1 cells, T/NK precursors in PB are considered to be contained in the pool of T/NK/myeloid multipotent progenitors. The age-associated increase in NK over T cell commitment might occur in precursor cells with T/NK/myeloid potential. PMID:23670190

Kyoizumi, Seishi; Kubo, Yoshiko; Kajimura, Junko; Yoshida, Kengo; Imai, Kazue; Hayashi, Tomonori; Nakachi, Kei; Young, Lauren F; Moore, Malcolm A; van den Brink, Marcel R M; Kusunoki, Yoichiro

2013-06-15

269

Age-associated changes in the differentiation potentials of human circulating hematopoietic progenitors to T- or NK-lineage cells  

PubMed Central

Age-associated changes of T- and NK-cell (T/NK) potential of human hematopoietic stem cells are unknown. Here, we enumerate and characterize T/NK precursors among CD34-positive/lineage marker-negative (CD34+Lin?) cell populations circulating in normal human adult peripheral blood (PB) by a limiting-dilution assay using co-culture with OP9-DL1 stroma cells expressing Notch 1 ligand, Delta-like 1. The frequency of T-cell precursors in CD34+Lin? cells was found to decrease with donor age, while the ratio of NK- to T-cell precursor frequency (NK/T ratio) increased with age, suggesting that lymphoid differentiation potential of PB progenitors shifts from T- to NK-cell lineage with aging. Clonal analyses of CD34+Lin? cells showed that differences in the NK/T ratio were attributable to different distributions of single- and dual-lineage T/NK precursor clones. Since nearly all of the clones retained monocyte and/or granulocyte differentiation potentials in co-culture with OP9-DL1 cells, T/NK precursors in PB are considered to be contained in the pool of T/NK/myeloid multi-potent progenitors. The age-associated increase in NK- over T-cell commitment might occur in precursor cells with T/NK/myeloid potential. PMID:23670190

Kyoizumi, Seishi; Kubo, Yoshiko; Kajimura, Junko; Yoshida, Kengo; Imai, Kazue; Hayashi, Tomonori; Nakachi, Kei; Young, Lauren F.; Moore, Malcolm A.; van den Brink, Marcel R.M.; Kusunoki, Yoichiro

2013-01-01

270

Caste specialization and differentiation in reproductive potential in the phylogenetically primitive ant Myrmecia gulosa  

Microsoft Academic Search

Summary. Division of labour is associated with morphological specialization in many species of social insects. Comparative data on phylogenetically “primitive” ants can help understand the selective forces promoting the production of multiple worker castes as well as the morphological divergence between queens and workers. We quantified size variations among workers and queen-worker dimorphism in the Myrmeciinae ant Myrmecia gulosa. Worker

V. Dietemann; B. Hölldobler; C. Peeters

2002-01-01

271

5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation  

PubMed Central

The therapeutic value of adipose-derived mesenchymal stem cells (Ad-MSCs) for bone regeneration is critically discussed. A possible reason for reduced osteogenic potential may be an age-related deterioration of the Ad-MSCs. In long term in vitro culture, epigenomic changes in DNA methylation are known to cause gene silencing, affecting stem cell growth as well as the differentiation potential. In this study, we observed an age-related decline in proliferation of primary human Ad-MSCs. Decreased Nanog, Oct4 and Lin28A and increased Sox2 gene-expression was accompanied by an impaired osteogenic differentiation potential of Ad-MSCs isolated from old donors (>60 a) as compared to Ad-MSCs isolated from younger donors (<45 a). 5-hydroxymethylcytosine (5 hmC) and 5-methylcytonsine (5 mC) distribution as well as TET gene expression were evaluated to assess the evidence of active DNA demethylation. We observed a decrease of 5 hmC in Ad-MSCs from older donors. Incubation of these cells with 5-Azacytidine induced proliferation and improved the osteogenic differentiation potential in these cells. The increase in AP activity and matrix mineralization was associated with an increased presence of 5 hmC as well as with an increased TET2 and TET3 gene expression. Our data show, for the first time, a decrease of DNA hydroxymethylation in Ad-MSCs which correlates with donor-age and that treatment with 5-Azacytidine provides an approach which could be used to rejuvenate Ad-MSCs from aged donors. PMID:24603866

Culmes, Mihaela; Bachmann, Anastasia; Seeliger, Claudine; Schyschka, Lilianna; Wang, Zhiyong; Rahmanian-Schwarz, Afshin; Stöckle, Ulrich; De Sousa, Paul A.; Pelisek, Jaroslav; Nussler, Andreas K.

2014-01-01

272

AT-101 downregulates BCL2 and MCL1 and potentiates the cytotoxic effects of lenalidomide and dexamethasone in preclinical models of multiple myeloma and Waldenström macroglobulinaemia  

PubMed Central

Summary Multiple myeloma, the second most common haematological malignancy in the U.S., is currently incurable. Disruption of the intrinsic apoptotic pathway by BCL2 and MCL1 upregulation is observed in >80% of myeloma cases and is associated with an aggressive clinical course. Remarkably, there is no approved drug with the ability to target BCL2 or MCL1. Thus, we investigated the anti-tumour effects of a pan-BCL2 inhibitor, AT-101, which has high binding specificity for BCL2 and MCL1 in preclinical models of plasma cell cancers (Multiple myeloma and Waldenström macroglobulinaemia). Gene expression and immunoblot analysis of six plasma cell cancer models showed upregulation of BCL2 family members. AT-101 was able to downregulate BCL2 and MCL1 in all plasma cell cancer models and induced apoptotic cell death in a caspase-dependent manner by altering mitochondrial membrane permeability. This cytotoxic effect and BCL2 downregulation were further potentiated when AT-101 was combined with lenalidomide/dexamethasone (LDA). NanoString nCounter mRNA quantification and Ingenuity Pathways Analysis revealed differential changes in the CCNA2, FRZB, FYN, IRF1, PTPN11 genes in LDA-treated cells. In summary, we describe for the first time the cellular and molecular events associated with the use of AT-101 in combination with lenalidomide/dexamethasone in preclinical models of plasma cell malignancy. PMID:24236538

Akhtar, Sharoon; Personett, David; Miller, Kena C.; Thompson, Kevin J.; Carr, Jennifer; Kumar, Shaji; Roy, Vivek; Ansell, Stephen M.; Mikhael, Joseph R.; Dispenzieri, Angela; Reeder, Craig B.; Rivera, Candido E.; Foran, James; Chanan-Khan, Asher

2015-01-01

273

Minimization of self-potential survey mis-ties acquired with multiple reference locations  

E-print Network

Self-potential (SP) surveys often involve many interconnected lines of data along available roads or trails, with the ultimate goal of producing a unique map of electric potentials at each station relative to a single ...

Minsley, Burke J.

274

Autoimmunity gene expression portrait: specific signature that intersects or differentiates between multiple sclerosis and systemic lupus erythematosus.  

PubMed

Autoimmune diseases are either tissue-specific like multiple sclerosis (MS) or multisystemic like systemic lupus erythematosus (SLE), although clinically both exhibit common features. To gain insight into the properties of the genes involved in each disease we have investigated the gene expression signature of peripheral blood mononuclear cells (PBMC) in MS and SLE in comparison to healthy subjects. Total RNA was purified, hybridized to Genechip array and analysed in 36 subjects (13 relapsing-remitting MS patients, five SLE patients and 18 age-matched healthy subjects that served as controls). Additional blood samples from 15 relapsing-remitting MS patients, 8 SLE patients and 10 healthy subjects were used for confirmation of microarray gene expression findings by ELISA and RT-PCR. MS and SLE patients demonstrated a common gene expression autoimmune signature of 541 genes which differentiated them from healthy subjects. The autoimmune signature included genes that encode proteins involved in apoptosis, cell cycle, inflammation and regulation of matrix metalloproteinase pathways. Specifically, decreased TIMP1 gene expression in the autoimmunity signature suggests increased MMP activity in target tissues as a result of the lack of feedback mechanism. An additional different disease specific signature identified the gene expression pattern for MS (1031 genes), mainly associated with over-expression of adhesion molecules and down-expression of heat shock proteins; the SLE specific signature (1146 genes) mainly involved DNA damage/repair pathways that result in production of nuclear autoantibodies. These results provide insights into the genetic pathways underlying autoimmune diseases, and identify specific disease-associated signatures that may enable targetted disease-related specific therapies to be developed. PMID:15373920

Mandel, M; Gurevich, M; Pauzner, R; Kaminski, N; Achiron, A

2004-10-01

275

Molecular mechanisms and potentials for differentiating inner ear stem cells into sensory hair cells.  

PubMed

In mammals, hair cells may be damaged or lost due to genetic mutation, infectious disease, chemical ototoxicity, noise and other factors, causing permanent sensorineural deafness. Regeneration of hair cells is a basic pre-requisite for recovery of hearing in deaf animals. The inner ear stem cells in the organ of Corti and vestibular utricle are the most ideal precursors for regeneration of inner ear hair cells. This review highlights some recent findings concerning the proliferation and differentiation of inner ear stem cells. The differentiation of inner ear stem cells into hair cells involves a series of signaling pathways and regulatory factors. This paper offers a comprehensive analysis of the related studies. PMID:24680894

Liu, Quanwen; Chen, Ping; Wang, Jinfu

2014-06-15

276

Sir2 Regulates Skeletal Muscle Differentiation as a Potential Sensor of the Redox State  

Microsoft Academic Search

Sir2 is a NAD+-dependent histone deacetylase that controls gene silencing, cell cycle, DNA damage repair, and life span. Prompted by the observation that the [NAD+]\\/[NADH] ratio is subjected to dynamic fluctuations in skeletal muscle, we have tested whether Sir2 regulates muscle gene expression and differentiation. Sir2 forms a complex with the acetyltransferase PCAF and MyoD and, when overexpressed, retards muscle

Marcella Fulco; R. Louis Schiltz; Simona Iezzi; M. Todd King; Po Zhao; Yoshihiro Kashiwaya; Eric Hoffman; Richard L. Veech; Vittorio Sartorelli

2003-01-01

277

Potential triggers of akinete differentiation in Nodularia spumigena (Cyanobacteriaceae) isolated from Australia  

Microsoft Academic Search

Nodularia spumigena, like many cyanobacteria, produces specialised reproductive structures, known as akinetes, which are believed to allow survival\\u000a under unfavourable conditions. This study investigated the effects of salinity, nitrogen and phosphorus concentration at two\\u000a irradiances on akinete differentiation in a N. spumigena isolate from the Gippsland Lakes, Victoria, Australia. A computer image analysis program was used to photograph filaments\\u000a and

Jackie H. Myers; John Beardall; Graeme Allinson; Scott Salzman; Simon Robertson; Leanne Gunthorpe

2011-01-01

278

The potential of dental stem cells differentiating into neurogenic cell lineage after cultivation in different modes in vitro.  

PubMed

Trauma or degenerative diseases of the central nervous system (CNS) cause the loss of neurons or glial cells. Stem cell transplantation has become a vital strategy for CNS regeneration. It is necessary to effectively induce nonneurogenic stem cells to differentiate into neurogenic cell lineages because of the limited source of neurogenic stem cells, relatively difficult cultivation, and ethical issues. Previous studies have found that dental stem cells can be used for transplantation therapy. The aim of this study was to explore a better inductive mode and time point for dental stem cells to differentiate into neural-like cells and evaluate a better candidate cell. In this study, dental follicle stem cells (DFSCs), dental papilla stem cells (DPSCs), and stem cells from apical papilla (SCAPs) were cultivated in five different modes. The proliferation ability, morphology, and expression of neural marker genes were analyzed. Results showed that DFSCs showed a higher proliferation potential. The proliferation was decreased after cultivation in chemical inductive medium as cultivation modes 3 and 5. The cells could present neural-like cell morphology after cultivation with human epidermal growth factor (EGF) and fibroblast growth factor-basic (bFGF) as cultivation modes 4 and 5. The vast majority of DFSCs gene expression levels in mode 4 on the third day was upregulated significantly. In conclusion, our data suggested that different dental stem cells exhibited different neural differentiation potentials. DFSCs might be the better candidate cell type. Furthermore, cultivation mode 4 and timing of the third day may promote differentiation into neurogenic cell lineages more effectively before transplantation to treat neurological diseases. PMID:25072651

Yang, Chao; Sun, Liang; Li, Xinghan; Xie, Li; Yu, Mei; Feng, Lian; Jiang, Zongting; Guo, Weihua; Tian, Weidong

2014-10-01

279

Swine Cone and Rod Precursors Arise Sequentially and Display Sequential and Transient Integration and Differentiation Potential Following Transplantation  

PubMed Central

Purpose. We followed cone and rod development in the pig and we correlated development with the potential for cone and rod precursor integration and differentiation following subretinal transplantation. Methods. Rod and cone precursors were identified during development by their position in the outer retina and by immunostaining for markers of differentiation. Embryonic retinal cells from green fluorescent protein (GFP)+ transgenic pigs at different developmental stages were transplanted into adult retinas and integration and differentiation was followed and quantified by immunostaining for markers of cone and rod differentiation. Results. Pig cones and rods are spatially segregated, allowing us to follow rod and cone development in situ. Gestation in the pig is 114 days. By embryonic day (E) 50, postmitotic cone progenitors had formed the outer two rows of the retina. These cone progenitors are marked by expression of Islet1 (ISL1) and Recoverin (RCVRN) (at this embryonic stage, RCVRN exclusively marks these cone precursors). By contrast, postmitotic neural retina leucine zipper (NRL)+ rod precursors, located interior to the cone precursors, did not appear until E65. At E50, before NRL+ rod precursors are evident, transplanted cells gave rise almost exclusively to cones. At, E57, transplanted cells gave rise to equal numbers of rods and cones, but by E65, transplanted cells gave rise almost exclusively to rods. Transplantation of cells at E85 or E105, as precursors initiate opsin expression, led to few integrated cells. Conclusions. Consistent with their sequential appearances in embryonic retina, these results demonstrate sequential and surprisingly narrow developmental windows for integration/differentiation of cone and rod precursors following transplantation. PMID:24327609

Wang, Wei; Zhou, Liang; Lee, Sang Joon; Liu, Yongqing; Fernandez de Castro, Juan; Emery, Douglas; Vukmanic, Eric; Kaplan, Henry J.; Dean, Douglas C.

2014-01-01

280

Measurements of jet multiplicity and differential production cross sections of Z +jets events in proton-proton collisions at ?{s }=7 TeV  

NASA Astrophysics Data System (ADS)

Measurements of differential cross sections are presented for the production of a Z boson and at least one hadronic jet in proton-proton collisions at ?{s }=7 TeV , recorded by the CMS detector, using a data sample corresponding to an integrated luminosity of 4.9 fb-1 . The jet multiplicity distribution is measured for up to six jets. The differential cross sections are measured as a function of jet transverse momentum and pseudorapidity for the four highest transverse momentum jets. The distribution of the scalar sum of jet transverse momenta is also measured as a function of the jet multiplicity. The measurements are compared with theoretical predictions at leading and next-to-leading order in perturbative QCD.

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; Adam, W.; Bergauer, T.; Dragicevic, M.; Erö, J.; Fabjan, C.; Friedl, M.; Frühwirth, R.; Ghete, V. M.; Hartl, C.; Hörmann, N.; Hrubec, J.; Jeitler, M.; Kiesenhofer, W.; Knünz, V.; Krammer, M.; Krätschmer, I.; Liko, D.; Mikulec, I.; Rabady, D.; Rahbaran, B.; Rohringer, H.; Schöfbeck, R.; Strauss, J.; Taurok, A.; Treberer-Treberspurg, W.; Waltenberger, W.; Wulz, C.-E.; Mossolov, V.; Shumeiko, N.; Suarez Gonzalez, J.; Alderweireldt, S.; Bansal, M.; Bansal, S.; Cornelis, T.; De Wolf, E. A.; Janssen, X.; Knutsson, A.; Luyckx, S.; Ochesanu, S.; Roland, B.; Rougny, R.; Van De Klundert, M.; Van Haevermaet, H.; Van Mechelen, P.; Van Remortel, N.; Van Spilbeeck, A.; Blekman, F.; Blyweert, S.; D'Hondt, J.; Daci, N.; Heracleous, N.; Keaveney, J.; Lowette, S.; Maes, M.; Olbrechts, A.; Python, Q.; Strom, D.; Tavernier, S.; Van Doninck, W.; Van Mulders, P.; Van Onsem, G. P.; Villella, I.; Caillol, C.; Clerbaux, B.; De Lentdecker, G.; Dobur, D.; Favart, L.; Gay, A. P. R.; Grebenyuk, A.; Léonard, A.; Mohammadi, A.; Perniè, L.; Reis, T.; Seva, T.; Thomas, L.; Vander Velde, C.; Vanlaer, P.; Wang, J.; Adler, V.; Beernaert, K.; Benucci, L.; Cimmino, A.; Costantini, S.; Crucy, S.; Dildick, S.; Fagot, A.; Garcia, G.; Mccartin, J.; Ocampo Rios, A. A.; Ryckbosch, D.; Salva Diblen, S.; Sigamani, M.; Strobbe, N.; Thyssen, F.; Tytgat, M.; Yazgan, E.; Zaganidis, N.; Basegmez, S.; Beluffi, C.; Bruno, G.; Castello, R.; Caudron, A.; Ceard, L.; Da Silveira, G. G.; Delaere, C.; du Pree, T.; Favart, D.; Forthomme, L.; Giammanco, A.; Hollar, J.; Jez, P.; Komm, M.; Lemaitre, V.; Nuttens, C.; Pagano, D.; Perrini, L.; Pin, A.; Piotrzkowski, K.; Popov, A.; Quertenmont, L.; Selvaggi, M.; Vidal Marono, M.; Vizan Garcia, J. M.; Beliy, N.; Caebergs, T.; Daubie, E.; Hammad, G. H.; Aldá Júnior, W. L.; Alves, G. A.; Brito, L.; Correa Martins Junior, M.; Dos Reis Martins, T.; Mora Herrera, C.; Pol, M. E.; Carvalho, W.; Chinellato, J.; Custódio, A.; Da Costa, E. M.; De Jesus Damiao, D.; De Oliveira Martins, C.; Fonseca De Souza, S.; Malbouisson, H.; Matos Figueiredo, D.; Mundim, L.; Nogima, H.; Prado Da Silva, W. L.; Santaolalla, J.; Santoro, A.; Sznajder, A.; Tonelli Manganote, E. J.; Vilela Pereira, A.; Bernardes, C. A.; Dogra, S.; Fernandez Perez Tomei, T. R.; Gregores, E. M.; Mercadante, P. G.; Novaes, S. F.; Padula, Sandra S.; Aleksandrov, A.; Genchev, V.; Iaydjiev, P.; Marinov, A.; Piperov, S.; Rodozov, M.; Stoykova, S.; Sultanov, G.; Tcholakov, V.; Vutova, M.; Dimitrov, A.; Glushkov, I.; Hadjiiska, R.; Kozhuharov, V.; Litov, L.; Pavlov, B.; Petkov, P.; Bian, J. G.; Chen, G. M.; Chen, H. S.; Chen, M.; Du, R.; Jiang, C. H.; Liang, S.; Plestina, R.; Tao, J.; Wang, X.; Wang, Z.; Asawatangtrakuldee, C.; Ban, Y.; Guo, Y.; Li, Q.; Li, W.; Liu, S.; Mao, Y.; Qian, S. J.; Wang, D.; Zhang, L.; Zou, W.; Avila, C.; Chaparro Sierra, L. F.; Florez, C.; Gomez, J. P.; Gomez Moreno, B.; Sanabria, J. C.; Godinovic, N.; Lelas, D.; Polic, D.; Puljak, I.; Antunovic, Z.; Kovac, M.; Brigljevic, V.; Kadija, K.; Luetic, J.; Mekterovic, D.; Sudic, L.; Attikis, A.; Mavromanolakis, G.; Mousa, J.; Nicolaou, C.; Ptochos, F.; Razis, P. A.; Bodlak, M.; Finger, M.; Finger, M.; Assran, Y.; Ellithi Kamel, A.; Mahmoud, M. A.; Radi, A.; Kadastik, M.; Murumaa, M.; Raidal, M.; Tiko, A.; Eerola, P.; Fedi, G.; Voutilainen, M.; Härkönen, J.; Karimäki, V.; Kinnunen, R.; Kortelainen, M. J.; Lampén, T.; Lassila-Perini, K.; Lehti, S.; Lindén, T.; Luukka, P.; Mäenpää, T.; Peltola, T.; Tuominen, E.; Tuominiemi, J.; Tuovinen, E.; Wendland, L.; Tuuva, T.; Besancon, M.; Couderc, F.; Dejardin, M.; Denegri, D.; Fabbro, B.; Faure, J. L.; Favaro, C.; Ferri, F.; Ganjour, S.; Givernaud, A.; Gras, P.; Hamel de Monchenault, G.; Jarry, P.; Locci, E.; Malcles, J.; Rander, J.; Rosowsky, A.; Titov, M.; Baffioni, S.; Beaudette, F.; Busson, P.; Charlot, C.; Dahms, T.; Dalchenko, M.; Dobrzynski, L.; Filipovic, N.; Florent, A.; Granier de Cassagnac, R.; Mastrolorenzo, L.; Miné, P.; Mironov, C.; Naranjo, I. N.; Nguyen, M.; Ochando, C.; Paganini, P.; Regnard, S.; Salerno, R.; Sauvan, J. B.; Sirois, Y.; Veelken, C.; Yilmaz, Y.; Zabi, A.; Agram, J.-L.; Andrea, J.; Aubin, A.; Bloch, D.; Brom, J.-M.; Chabert, E. C.; Collard, C.; Conte, E.; Fontaine, J.-C.; Gelé, D.; Goerlach, U.; Goetzmann, C.; Le Bihan, A.-C.; Van Hove, P.; Gadrat, S.; Beauceron, S.; Beaupere, N.; Boudoul, G.; Bouvier, E.; Brochet, S.; Carrillo Montoya, C. A.; Chasserat, J.; Chierici, R.; Contardo, D.; Depasse, P.; El Mamouni, H.; Fan, J.; Fay, J.; Gascon, S.; Gouzevitch, M.; Ille, B.; Kurca, T.; Lethuillier, M.; Mirabito, L.; Perries, S.; Ruiz Alvarez, J. D.; Sabes, D.; Sgandurra, L.; Sordini, V.; Vander Donckt, M.; Verdier, P.; Viret, S.; Xiao, H.

2015-03-01

281

Differential charging of high-voltage spacecraft - The equilibrium potential of insulated surfaces  

NASA Technical Reports Server (NTRS)

A theory is presented for the steady-state potential of insulated surfaces near exposed high voltages. The term 'insulated surfaces' is used to mean either dielectric surfaces or electrically isolated metallic surfaces. The potential is bounded below by the zero of the material's I-V curve assuming total suppression of secondary electrons, and above by assuming total extraction of secondaries. Within these bounds, the material's surface potential is determined consistently with the solution to Poisson's equation external to the vehicle. The theory is compared with rocket experiments and with SCATHA satellite data. Also, an explanation is suggested for the observed 'snapover' of solar cell coverslips from near plasma ground potential to near the potential of positively biased interconnects with increasing bias voltage.

Katz, I.; Mandell, M. J.

1982-01-01

282

Differential Regulation by Organic Compounds and Heavy Metals of Multiple Laccase Genes in the Aquatic Hyphomycete Clavariopsis aquatica  

PubMed Central

To advance the understanding of the molecular mechanisms controlling microbial activities involved in carbon cycling and mitigation of environmental pollution in freshwaters, the influence of heavy metals and natural as well as xenobiotic organic compounds on laccase gene expression was quantified using quantitative real-time PCR (qRT-PCR) in an exclusively aquatic fungus (the aquatic hyphomycete Clavariopsis aquatica) for the first time. Five putative laccase genes (lcc1 to lcc5) identified in C. aquatica were differentially expressed in response to the fungal growth stage and potential laccase inducers, with certain genes being upregulated by, e.g., the lignocellulose breakdown product vanillic acid, the endocrine disruptor technical nonylphenol, manganese, and zinc. lcc4 is inducible by vanillic acid and most likely encodes an extracellular laccase already excreted during the trophophase of the organism, suggesting a function during fungal substrate colonization. Surprisingly, unlike many laccases of terrestrial fungi, none of the C. aquatica laccase genes was found to be upregulated by copper. However, copper strongly increases extracellular laccase activity in C. aquatica, possibly due to stabilization of the copper-containing catalytic center of the enzyme. Copper was found to half-saturate laccase activity already at about 1.8 ?M, in favor of a fungal adaptation to low copper concentrations of aquatic habitats. PMID:22544244

Solé, Magali; Müller, Ines; Pecyna, Marek J.; Fetzer, Ingo; Harms, Hauke

2012-01-01

283

Isolation, characterization and the multi-lineage differentiation potential of rabbit bone marrow-derived mesenchymal stem cells  

PubMed Central

Mesenchymal stem cells (MSCs) are recognized by their plastic adherent ability, fibroblastic-like appearance, expression of specific surface protein markers, and are defined by their ability to undergo multi-lineage differentiation. Although rabbit bone marrow-derived MSCs (rbMSCs) have been used extensively in previous studies especially in translational research, these cells have neither been defined morphologically and ultrastructurally, nor been compared with their counterparts in humans in their multi-lineage differentiation ability. A study was therefore conducted to define the morphology, surface marker proteins, ultrastructure and multi-lineage differentiation ability of rbMSCs. Herein, the primary rbMSC cultures of three adult New Zealand white rabbits (at least 4 months old) were used for three independent experiments. rbMSCs were isolated using the gradient-centrifugation method, an established technique for human MSCs (hMSCs) isolation. Cells were characterized by phase contrast microscopy observation, transmission electron microscopy analysis, reverse transcriptase-polymerase chain reaction (PCR) analysis, immunocytochemistry staining, flow cytometry, alamarBlue® assay, histological staining and quantitative (q)PCR analysis. The isolated plastic adherent cells were in fibroblastic spindle-shape and possessed eccentric, irregular-shaped nuclei as well as rich inner cytoplasmic zones similar to that of hMSCs. The rbMSCs expressed CD29, CD44, CD73, CD81, CD90 and CD166, but were negative (or dim positive) for CD34, CD45, CD117 and HLD-DR. Despite having similar morphology and phenotypic expression, rbMSCs possessed significantly larger cell size but had a lower proliferation rate as compared with hMSCs. Using established protocols to differentiate hMSCs, rbMSCs underwent osteogenic, adipogenic and chondrogenic differentiation. Interestingly, differentiated rbMSCs demonstrated higher levels of osteogenic (Runx2) and chondrogenic (Sox9) gene expressions than that of hMSCs (P < 0.05). There was, however, no difference in the adipogenic (Ppar?) expressions between these cell types (P > 0.05). rbMSCs possess similar morphological characteristics to hMSCs, but have a higher potential for osteogenic and chondrogenic differentiation, despite having a lower cell proliferation rate than hMSCs. The characteristics reported here may be used as a comprehensive set of criteria to define or characterize rbMSCs. PMID:23510053

Tan, Sik-Loo; Ahmad, Tunku Sara; Selvaratnam, Lakshmi; Kamarul, Tunku

2013-01-01

284

DISTRIBUTED COOPERATIVE CONTROL OF MULTIPLE VEHICLE FORMATIONS USING STRUCTURAL POTENTIAL FUNCTIONS 1  

Microsoft Academic Search

In this paper, we propose a framework for formation stabilization of multiple autonomous vehicles in a distributed fashion. Each vehicle is assumed to have simple dynamics, i.e. a double-integrator, with a directed (or an undirected) information flow over the formation graph of the vehicles. Our goal is to find a distributed control law (with an ecient computational cost) for each

Reza Olfati-Saber; Richard M. Murray

285

Shrub Encroachment Impacts the Potential for Multiple Use Conflicts on Public Land  

Microsoft Academic Search

Public rangelands in North America are typically managed under a multiple use policy that includes livestock grazing and wildlife management. In this article we report on the landscape level extent of grassland loss to shrub encroachment in a portion of the Rocky Mountain Forest Reserve in southwestern Alberta, Canada, and review the associated implications for simultaneously supporting livestock and wildlife

Angela M. Burkinshaw; Edward W. Bork

2009-01-01

286

Greenhouse and Field Evaluation of Multiple Virus Resistant Lagenaria siceraria Lines Potentially useful for Watermelon Rootstocks  

Technology Transfer Automated Retrieval System (TEKTRAN)

In previous evaluations we identified numerous lines of bottle gourd (Lagenaria siceraria) with complete or partial resistance to Zucchini yellow mosaic virus (ZYMV). In the present study, we were interested in developing bottle gourd lines with multiple virus resistance that could be useful as roo...

287

The Potential of Water Vapor & Precipitation Estimation with a Differential-frequency Radar  

NASA Technical Reports Server (NTRS)

In the presence of rain, the radar return powers from a three-frequency radar, with center frequency at 22.235 GHz and upper and lower frequencies chosen with equal water vapor absorption coefficients, can be used to estimate water vapor density and parameters of the precipitation. A linear combination of differential measurements between the center and lower frequencies on one hand and the upper and lower frequencies on the other provide an estimate of differential water vapor absorption. Conversely, the difference in radar reflectivity factors (in dB) between the upper and lower frequencies is independent of water vapor absorption and can be used to estimate the median mass diameter of the hydrometeors. For a down-looking radar, path-integrated estimates of water vapor absorption may be possible under rain-free as well as raining conditions by using the surface returns at the three frequencies. Cross-talk or interference between the precipitation and water vapor estimates depends on the frequency separation of the channels as well as on the phase state and the median mass diameter of the hydrometeors. Simulations of the retrieval of water vapor absorption show that the largest source of variability arises from the variance in the measured radar return powers while the largest biases occur in the mixed-phase region. Use of high pulse repetition frequencies and signal whitening methods may be needed to obtain the large number of independent samples required. Measurements over a fractional bandwidth, defined as the ratio of the difference between the upper and lower frequencies to the center frequency, up to about 0.2 should be passible in a differential frequency mode, where a single transceiver and antenna are used. Difficulties in frequency allocation may require alternative choices of frequency where the water vapor absorptions at the low and high frequencies are unequal. We consider the degradation in the retrieval accuracy when the frequencies are not optimum.

Meneghini, Robert; Liao, Liang; Tian, Lin

2006-01-01

288

In vivo differentiation potential of buffalo (Bubalus bubalis) embryonic stem cell.  

PubMed

Embryonic stem cells (ESCs) derived from inner cell mass (ICM) of mammalian blastocyst are having indefinite proliferation and differentiation capability for any type of cell lineages. In the present study, ICMs of in vitro-derived buffalo blastocysts were cultured into two different culture systems using buffalo fetal fibroblast as somatic cell support and Matrigel as synthetic support to obtain pluripotent buffalo embryonic stem cell (buESC) colonies. Pluripotency of the ESCs were characterised through pluripotency markers whereas, their differentiation capability was assessed by teratoma assay using immuno-compromised mice. Cumulus ooccyte complexes from slaughter house-derived ovaries were subjected to in vitro maturation, in vitro fertilization and in vitro culture to generate blastocysts. Total 262 blastocysts were derived through IVEP with 11.83 % (31/262) hatching rate. To generate buESCs, 15 ICMs from hatched blastocysts were cultured on mitomycin-C-treated homologous fetal fibroblast feeder layer, whereas the leftover 16 ICMs were cultured on extra-cellular matrix (Matrigel). No significant differences were observed for primary ESCs colony formation between two culture systems. Primary colonies as well as passaged ESCs were characterised by alkaline phosphatase staining, karyotyping and expression of transcription-based stem cell markers, OCT-4 and cell surface antigens SSEA-4 and TRA-1-60. Batch of ESCs found positive for pluripotency markers and showing normal karyotype after fifteenth passage were inoculated into eight immuno-compromised mice through subcutaneous and intramuscular route. Subcutaneous route of inoculation was found to be better than intramuscular route. Developed teratomas were excised surgically and subjected to histological analysis. Histological findings revealed presence of all the three germinal layer derivatives in teratoma sections. Presence of germinal layer derivatives were further confirmed by reverse transcriptase-polymerase chain reaction for the presence of differentiation markers like nerve cell adhesion molecule, fetal liver kinase-1 and alpha-feto protein for ectoderm, mesoderm and endoderm, respectively. PMID:22678753

Verma, Om Prakash; Kumar, Rajesh; Nath, Amar; Sharma, Manjinder; Dubey, Pawan Kumar; Kumar, G Sai; Sharma, G Taru

2012-06-01

289

Differential Detection of Potentially Hazardous Fusarium Species in Wheat Grains by an Electronic Nose  

PubMed Central

Fungal infestation on wheat is an increasingly grave nutritional problem in many countries worldwide. Fusarium species are especially harmful pathogens due to their toxic metabolites. In this work we studied volatile compounds released by F. cerealis, F. graminearum, F. culmorum and F. redolens using SPME-GC/MS. By using an electronic nose we were able to differentiate between infected and non-infected wheat grains in the post-harvest chain. Our electronic nose was capable of distinguishing between four wheat Fusaria species with an accuracy higher than 80%. PMID:21695232

Eifler, Jakob; Martinelli, Eugenio; Santonico, Marco; Capuano, Rosamaria; Schild, Detlev; Di Natale, Corrado

2011-01-01

290

Investigation of potential of differential absorption Lidar techniques for remote sensing of atmospheric pollutants  

NASA Technical Reports Server (NTRS)

The NASA multipurpose differential absorption lidar (DIAL) system uses two high conversion efficiency dye lasers which are optically pumped by two frequency-doubled Nd:YAG lasers mounted rigidly on a supporting structure that also contains the transmitter, receiver, and data system. The DIAL system hardware design and data acquisition system are described. Timing diagrams, logic diagrams, and schematics, and the theory of operation of the control electronics are presented. Success in obtaining remote measurements of ozone profiles with an airborne systems is reported and results are analyzed.

Butler, C. F.; Shipley, S. T.; Allen, R. J.

1981-01-01

291

Regulation of differentiation- and proliferation-inducers on Lewis antigens, ?-fucosyltransferase and metastatic potential in hepatocarcinoma cells  

Microsoft Academic Search

The expressions of Lewis (Le) antigens, ?-1,3\\/1,4 fucosyltransferases (?-1,3\\/1,4 FuTs), and metastatic potential after the treatment of 2 differentiation inducers, all-trans retinoic acid (ATRA), 8-bromo-cyclic 3?,5?adenosine monophosphate (8-Br-cAMP); and 2 proliferation inducers, epidermal growth factor (EGF) and phobol-12-myristate-13-acetate (PMA), on 7721 human hepatocarcinoma cell line were studied. Cell adhesion to human umbilical vein endothelial cells (HUVEC), cell migration through transwell

F Liu; H-L Qi; H-L Chen

2001-01-01

292

Personality traits as potential susceptibility markers: differential susceptibility to support among parents.  

PubMed

In this study, we examined whether parents are differentially susceptible to support from their spouse and adolescent child depending on their personality traits, and whether differences in susceptibility to support among parents, in turn, are linked to the quality of support parents give to their children. Participants in this three-wave longitudinal study were 288 two-parent Dutch families with an adolescent child. Fathers were on average 43.9 years old (SD?=?3.7 years), mothers were 41.7 years old (SD?=?3.3 years), and adolescents (50% girls) were 14.5 years old (SD?=?0.8 years). We found that the association between support from children toward their parents and subsequent support from parents toward their children was more pronounced for parents high on Openness, for better and for worse. Extraversion, Agreeableness, Conscientiousness, and Emotional Stability did not emerge as markers of differences in susceptibility. Also, parents did not differ in their susceptibility to support from their spouse, nor were differences in susceptibility found a year later when using data from a third wave. We found very modest support for differential susceptibility, only for Openness, and depending on the source of perceived support and on the timing of measurement. PMID:24471708

Slagt, Meike; Dubas, Judith Semon; Denissen, Jaap J A; Dekovi?, Maja; van Aken, Marcel A G

2015-04-01

293

Expression of miRNAs in ovine fetal gonads: potential role in gonadal differentiation  

PubMed Central

Background Gonadal differentiation in the mammalian fetus involves a complex dose-dependent genetic network. Initiation and progression of fetal ovarian and testicular pathways are accompanied by dynamic expression patterns of thousands of genes. We postulate these expression patterns are regulated by small non-coding RNAs called microRNAs (miRNAs). The aim of this study was to identify the expression of miRNAs in mammalian fetal gonads using sheep as a model. Methods We determined the expression of 128 miRNAs by real time PCR in early-gestational (gestational day (GD) 42) and mid-gestational (GD75) sheep ovaries and testes. Expression data were further examined and validated by bioinformatic analysis. Results Expression analysis revealed significant differences between ovaries and testes among 24 miRNAs at GD42, and 43 miRNAs at GD75. Bioinformatic analysis revealed that a number of differentially expressed miRNAs are predicted to target genes known to be important in mammalian gonadal development, including ESR1, CYP19A1, and SOX9. In situ hybridization revealed miR-22 localization within fetal testicular cords. As estrogen signaling is important in human and sheep ovarian development, these data indicate that miR-22 is involved in repressing estrogen signaling within fetal testes. Conclusions Based on our results we postulate that gene expression networks underlying fetal gonadal development are regulated by miRNAs. PMID:21223560

2011-01-01

294

X-ray induced alterations in the differentiation and mineralization potential of murine preosteoblastic cells  

NASA Astrophysics Data System (ADS)

To evaluate the effects of ionizing radiation (IR) on murine preosteoblastic cell differentiation, we directed OCT-1 cells to the osteoblastic lineage by treatment with a combination of ?-glycerophosphate (?-GP), ascorbic acid (AA), and dexamethasone (Dex). In vitro mineralization was evaluated based on histochemical staining and quantification of the hydroxyapatite content of the extracellular bone matrix. Expression of mRNA encoding Runx2, transforming growth factor ?1 (TGF-?1), osteocalcin (OCN), and p21CDKN1A was analyzed. Exposure to IR reduced the growth rate and diminished cell survival of OCT-1 cells under standard conditions. Notably, calcium content analysis revealed that deposition of mineralized matrix increased significantly under osteogenic conditions after X-ray exposure in a time-dependent manner. In this study, higher radiation doses exert significant overall effects on TGF-?1, OCN, and p21CDKN1A gene expression, suggesting that gene expression following X-ray treatment is affected in a dose-dependent manner. Additionally, we verified that Runx2 was suppressed within 24 h after irradiation at 2 and 4 Gy. Although further studies are required to verify the molecular mechanism, our observations strongly suggest that treatment with IR markedly alters the differentiation and mineralization process of preosteoblastic cells.

Hu, Yueyuan; Lau, Patrick; Baumstark-Khan, Christa; Hellweg, Christine E.; Reitz, Günther

2012-05-01

295

Cellular mechanical properties reflect the differentiation potential of adipose-derived mesenchymal stem cells.  

PubMed

The mechanical properties of adipose-derived stem cell (ASC) clones correlate with their ability to produce tissue-specific metabolites, a finding that has dramatic implications for cell-based regenerative therapies. Autologous ASCs are an attractive cell source due to their immunogenicity and multipotent characteristics. However, for practical applications ASCs must first be purified from other cell types, a critical step which has proven difficult using surface-marker approaches. Alternative enrichment strategies identifying broad categories of tissue-specific cells are necessary for translational applications. One possibility developed in our lab uses single-cell mechanical properties as predictive biomarkers of ASC clonal differentiation capability. Elastic and viscoelastic properties of undifferentiated ASCs were tested via atomic force microscopy and correlated with lineage-specific metabolite production. Cell sorting simulations based on these "mechanical biomarkers" indicated they were predictive of differentiation capability and could be used to enrich for tissue-specific cells, which if implemented could dramatically improve the quality of regenerated tissues. PMID:22615348

González-Cruz, Rafael D; Fonseca, Vera C; Darling, Eric M

2012-06-12

296

Cerebellar Ataxia from Multiple Potential Causes: Hypothyroidism, Hashimoto's Thyroiditis, Thalamic Stimulation, and Essential Tremor  

PubMed Central

Background Both hypothyroidism and Hashimoto's thyroiditis (HT) can rarely be associated with cerebellar ataxia. Severe essential tremor (ET) as well as bilateral thalamic deep brain stimulation (DBS) may lead to subtle cerebellar signs. Case Report We report a 74-year-old male with hypothyroidism and a 20-year history of ET who developed cerebellar ataxia after bilateral thalamic DBS. Extensive workup revealed elevated thyroid stimulating hormone and thyroperoxidase antibody titers confirming the diagnosis of HT. Discussion Our case demonstrates multiple possible causes of cerebellar ataxia in a patient, including hypothyroidism, HT, chronic ET, and bilateral thalamic DBS. Counseling of patients may be appropriate when multiple risk factors for cerebellar ataxia coexist in one individual. PMID:23439792

Shneyder, Natalya; Lyons, Mark K.; Driver-dunckley, Erika; Evidente, Virgilio Gerald H.

2012-01-01

297

A DELAY DIFFERENTIAL MODEL FOR EL NINO/SOUTHERN OSCILLATION (ENSO): PULLBACK ATTRACTORS, PHASE LOCKING, AND MULTIPLE SOLUTIONS  

NASA Astrophysics Data System (ADS)

We consider a highly idealized model for El Nino/Southern Oscillation (ENSO) variability, previously studied by two of the co-authors. The model is governed by a delay differential equation for sea surface temperature T in the Tropical Pacific, and it combines two key mechanisms that participate in ENSO dynamics: delayed negative feedback and seasonal forcing. We perform a theoretical and numerical study of the model in the three-dimensional space of its physically relevant parameters: strength of seasonal forcing, atmosphere-ocean coupling, and propagation period of oceanic waves across the Tropical Pacific. Phase locking of model solutions to the periodic forcing is prevalent: the local maxima and minima of the solutions tend to occur at the same position within the seasonal cycle. Such phase locking is a key feature of the observed El Nino (warm) and La Nina (cold) events. The phasing of the extrema within the seasonal cycle depends sensitively on model parameters when forcing is weak. We also study co-existence of multiple solutions for fixed model parameters and describe the basins of attraction of the stable solutions within a one-dimensional manifold of constant initial model histories. We study next a two-dimensional manifold of solutions, given by initial histories that are piecewise constant, with a jump from T = a to T = 0 that occurs at time t = -b. To do so, we apply the concept of pullback attractor (PBA) in order to study the model dynamics in the model-parameter region where sensitivity to parameter values is high. Computation of the model's PBAs clearly demonstrates that its dynamics --- whether periodic or quasi-periodic --- occurs on a two-dimensional torus, within the three-dimensional space generated by the "product" of the two-dimensional manifold parameterized by (a,b) with the model variable T. This behavior reflects the competition between two oscillatory mechanisms: an external one due to the seasonal forsing and an internal one due to the delayed feedbacks. Such an interpretation is much harder to obtain from the complex, parameter-sensitive dynamics of the model using more traditional, theoretical and numerical, approaches.

Chekroun, M. D.; Zaliapin, I.; Ghil, M.

2009-12-01

298

Shrub Encroachment Impacts the Potential for Multiple Use Conflicts on Public Land  

Microsoft Academic Search

Public rangelands in North America are typically managed under a multiple use policy that includes livestock grazing and wildlife\\u000a management. In this article we report on the landscape level extent of grassland loss to shrub encroachment in a portion of\\u000a the Rocky Mountain Forest Reserve in southwestern Alberta, Canada, and review the associated implications for simultaneously\\u000a supporting livestock and wildlife

Angela M. Burkinshaw; Edward W. Bork

2009-01-01

299

The potential of panobinostat as a treatment option in patients with relapsed and refractory multiple myeloma  

PubMed Central

Panobinostat is an investigational and potent histone deacetylase inhibitor (HDACi) that has shown promise as an antimultiple myeloma agent in the preclinical setting. In this review, we discuss the rationale for the use of panobinostat as a combination therapy for multiple myeloma and provide an overview of recent and ongoing clinical trials testing the safety and efficacy of panobinostat for the treatment of the disease. PMID:25469210

Andreu-Vieyra, Claudia V.

2014-01-01

300

Inhibition of bacterial multiplication by the iron chelator deferoxamine: Potentiating effect of ascorbic acid  

Microsoft Academic Search

Since iron is essential for the multiplication of microorganisms, the effect of the iron chelator deferoxamine, with or without ascorbic acid, on the growth of 43 strains ofStaphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Alcaligenes faecalis, Neisseria meningitidis and species ofSalmonella, Enterobacter, Pseudomonas andProvidencia, was investigated with the use of an automated turbidimeter. Addition of deferoxamine (25–400?g\\/ml)

B. S. van Asbeck; J. H. Marcelis; J. J. M. Marx; A. Struyvenberg; J. H. van Kats; J. Verhoef

1983-01-01

301

UNAIDS ‘multiple sexual partners’ core indicator: promoting sexual networks to reduce potential biases  

PubMed Central

UNAIDS proposed a set of core indicators for monitoring changes in the worldwide AIDS epidemic. This paper explores the validity and effectiveness of the ‘multiple sexual partners’ core indicator, which is only partially captured with current available data. The paper also suggests an innovative approach for collecting more informative data that can be used to provide an accurate measure of the UNAIDS’s ‘multiple sexual partners’ core indicator. Specifically, the paper addresses three major limitations associated with the indicator when it is measured with respondents’ sexual behaviors. First, the indicator assumes that a person’s risk of contracting HIV/AIDS/STIs is merely a function of his/her own sexual behavior. Second, the indicator does not account for a partner’s sexual history, which is very important in assessing an individual’s risk level. Finally, the 12-month period used to define a person’s risks can be misleading, especially because HIV/AIDS theoretically has a period of latency longer than a year. The paper concludes that, programmatically, improvements in data collection are a top priority for reducing the observed bias in the ‘multiple sexual partners’ core indicator. PMID:24647127

Dimbuene, Zacharie Tsala; Emina, Jacques B.O.; Sankoh, Osman

2014-01-01

302

Haematopoietic stem cells in spleen have distinct differentiative potential for antigen presenting cells  

PubMed Central

Abstract Dendritic cells (DC) are known to develop from macrophage dendritic progenitors (MDP) in bone marrow (BM), which give rise to conventional (c)DC and monocytes, both dominant antigen presenting cell (APC) subsets in spleen. This laboratory has however defined a distinct dendritic-like cell subset in spleen (L-DC), which can also be derived in long-term cultures of spleen. In line with the restricted in vitro development of only L-DC in these stromal cultures, we questioned whether self-renewing HSC or progenitors exist in spleen with restricted differentiative capacity for only L-DC. Neonatal spleen and BM were compared for their ability to reconstitute mice and to give rise to L-DC, as well as other splenic APC. Neonatal spleen cells were transplanted into allotype-distinct lethally irradiated hosts along with host-type competitor BM cells, and assayed over 8 to 51 weeks for haematopoietic reconstitution of L-DC and cDC subsets, along with other lymphoid and myeloid cells. In this study, neonatal spleen showed multilineage haematopoietic reconstitution in mouse chimeras, rather than specific or restricted ability to differentiate into L-DC. However, the representation of individual APC subsets was found to be unequal in chimeras partially reconstituted with donor cells, such that more donor-derived progeny were seen for L-DC than for myeloid and cDC subsets. The ability of HSC in spleen to develop into L-DC was indicated by a strong bias in the subset size of these cells over other splenic APC subsets. This type of evidence supports a model whereby spleen represents an important site for haematopoiesis of this distinct DC subset. The conditions under which haematopoiesis of L-DC occurs in spleen, or the progenitors involved, will require further investigation. PMID:19799644

Tan, Jonathan KH; O’Neill, Helen C

2010-01-01

303

Sexual differentiation in the distribution potential of northern jaguars (Panthera onca)  

USGS Publications Warehouse

We estimated the potential geographic distribution of jaguars in the southwestern United States and northwestern Mexico by modeling the jaguar ecological niche from occurrence records. We modeled separately the distribution of males and females, assuming records of females probably represented established home ranges while male records likely included dispersal movements. The predicted distribution for males was larger than that for females. Eastern Sonora appeared capable for supporting male and female jaguars with potential range expansion into southeastern Arizona. New Mexico and Chihuahua contained environmental characteristics primarily limited to the male niche and thus may be areas into which males occasionally disperse.

Boydston, Erin E.; Lopez Gonzalez, Carlos A.

2005-01-01

304

Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials  

SciTech Connect

Cell therapy with bone marrow multipotential stromal cells/mesenchymal stem cells (MSCs) represents a promising approach in the field of regenerative medicine. Low frequency of MSCs in adult bone marrow necessitates ex vivo expansion of MSCs after harvest; however, such a manipulation causes cellular senescence with loss of differentiation, proliferative, and therapeutic potentials of MSCs. Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities. Interestingly, 3% hydrogen gas treatment did not decrease hydroxyl radical, protein carbonyl, and 8-hydroxydeoxyguanosine, suggesting that scavenging hydroxyl radical might not be responsible for these effects of hydrogen gas in this study.

Kawasaki, Haruhisa [Department of Pathology, The Ohio State University, Columbus, OH 43210 (United States) [Department of Pathology, The Ohio State University, Columbus, OH 43210 (United States); Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210 (United States); Guan, Jianjun [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States)] [Department of Materials Science and Engineering, The Ohio State University, Columbus, OH 43210 (United States); Tamama, Kenichi, E-mail: kenichi.tamama@osumc.edu [Department of Pathology, The Ohio State University, Columbus, OH 43210 (United States) [Department of Pathology, The Ohio State University, Columbus, OH 43210 (United States); Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210 (United States); Center for Stem Cell and Regenerative Medicine, The Ohio State University, Columbus, OH 43210 (United States)

2010-07-02

305

Toll-like receptors as potential therapeutic targets for multiple diseases  

Microsoft Academic Search

The family of Toll-like receptors (TLRs) is receiving considerable attention as potential regulators and controllers of the immune response through their ability to recognize pathogen-associated molecular patterns. The discovery that endogenous ligands, as well as microbial components, are recognized by TLRs, and that small-molecular-mass synthetic compounds activate TLRs, raised interest in these receptors as potential targets for the development of

Claudia Zuany-Amorim; John Hastewell; Christoph Walker

2002-01-01

306

Identification of the Dopamine D3 Receptor in Oligodendrocyte Precursors: Potential Role in Regulating Differentiation and  

E-print Network

Identification of the Dopamine D3 Receptor in Oligodendrocyte Precursors: Potential Role mark- ers of specific stages of oligodendrocyte development indi- cated that D3r expression occurred in precursors and in imma- ture oligodendrocytes but not in mature oligodendrocytes (i.e., A2B5 007 01 and A2B5

Bongarzone, Ernesto R.

307

Exposure to Potentially Traumatic Events in Early Childhood: Differential Links to Emergent Psychopathology  

ERIC Educational Resources Information Center

Research NeedsObjective: To examine associations between exposure to potentially traumatic events (PTEs) and clinical patterns of symptoms and disorders in preschool children. Method: Two hundred and thirteen referred and non-referred children, ages 24 to 48 months (MN = 34.9, SD = 6.7 months) were studied. Lifetime exposure to PTEs (family…

Briggs-Gowan, Margaret J.; Carter, Alice S.; Clark, Roseanne; Augustyn, Marilyn; McCarthy, Kimberly J.; Ford, Julian D.

2010-01-01

308

Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells.  

PubMed

NK-cells undergo a "licensing" process as they develop into fully-functional cells capable of efficiently killing targets. NK-cell differentiation is accompanied by an increased surface expression of inhibitory killer immunoglobulin-like receptor (KIR) molecules, which is positively associated with cytotoxicity against the HLA-deficient K562 cell line. NK-cells are rapidly redeployed between the blood and tissues in response to acute exercise, but it is not known if exercise evokes a preferential trafficking of differentiated NK-cells or impacts NK-cell cytotoxic activity (NKCA) against HLA-expressing target cells. Sixteen healthy cyclists performed three 30-min bouts of cycling exercise at -5%, +5%, and +15% of lactate threshold. Blood samples obtained before, immediately after, and 1h after exercise were used to enumerate NK-cells and their subsets, and determine NKCA and degranulating subsets (CD107+) against cell lines of multiple myeloma (U266 and RPMI-8226), lymphoma (721.221 and 221 AEH), and leukemia (K562) origin by 4 and 10-color flow cytometry, respectively. Exercise evoked a stepwise redeployment of NK-cell subsets in accordance with differentiation status [highly-differentiated (KIR+/NKG2A-) >medium-differentiated (KIR+/NKG2A+)>low-differentiated (KIR-/NKG2A+)] that was consistent across all exercise intensities. NKCA per cell increased ?1.6-fold against U266 and 221 AEH targets 1h post-exercise and was associated with a decreased proportion of NK-cells expressing the inhibitory receptor CD158b and increased proportion of NK-cells expressing the activating receptor NKG2C, respectively. We conclude that exercise evokes a preferential redeployment of NK-cell subsets with a high differentiation phenotype and augments cytotoxicity against HLA-expressing target cells. Exercise may serve as a simple strategy to enrich the blood compartment of highly cytotoxic NK-cell subsets that can be harvested for clinical use. PMID:24200514

Bigley, Austin B; Rezvani, Katayoun; Chew, Claude; Sekine, Takuya; Pistillo, Mira; Crucian, Brian; Bollard, Catherine M; Simpson, Richard J

2014-07-01

309

Multiple Continua Simulations of Thermal-Hydrological-Chemical Processes in the Potential Repository at Yucca Mountain, Nevada  

NASA Astrophysics Data System (ADS)

Numerical simulation of nonisothermal, multiphase flow and associated reactive transport in fractured rock is an important tool for evaluating the performance of a potential repository for high-level nuclear waste at Yucca Mountain, Nevada. A dual continuum representation has emerged as the standard approach for modeling processes in the unsaturated zone near emplacement tunnels. In the dual continuum representation, the fracture network is modeled as an equivalent continuum that interacts with a second continuum representing the matrix system. The principal limitation of the dual continuum approach is that it neglects gradients in pressure, temperature, saturation, and concentration within the matrix blocks. The dual continuum model is understood to be an accurate approximation for steady-state or weakly transient situations, but the accuracy of the representation is unclear for strongly heated transient situations. Thermal-hydrological-chemical simulations using the dual continuum model have been compared with simulations using the more general multiple interacting continua (MINC) model (Pruess and Narasimhan, 1985). In the MINC model, multiple interacting continua are used to represent the matrix system. Both the MINC and dual continuum simulations use the computer code MULTIFLO Version 2.0.1 (Lichtner and Seth, 1996; Painter and Seth, 2003), and consider multiple aqueous species and multiple minerals. The MINC simulations result in lower matrix pressures and drier fractures near the potential emplacement tunnels. Precipitation of amorphous silica in fractures is reduced in the MINC model. This abstract was prepared to document work performed by the Center for Nuclear Waste Regulatory Analyses (CNWRA) and its contractors for the Nuclear Regulatory Commission (NRC) under Contract No. NRC-02-02-012. The activities reported here were performed on behalf of the NRC Office of Nuclear Material Safety and Safeguards, Division of High-Level Waste Repository Safety. This abstract is an independent product of the CNWRA and does not necessarily reflect the view or regulatory position of NRC.

Painter, S.; Pabalan, R. T.; Sun, A. Y.

2005-12-01

310

Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines  

Microsoft Academic Search

Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated -irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of -irradiation. Repeated TMZ doses were given before and concurrent

Krista A. van Nifterik; Jaap van den Berg; Lukas J. A. Stalpers; M. Vincent M. Lafleur; Sieger Leenstra; Ben J. Slotman; Theo J. M. Hulsebos; Peter Sminia

2007-01-01

311

Adult stem cells and their trans-differentiation potential—perspectives and therapeutic applications  

Microsoft Academic Search

Stem cells are self-renewing multipotent progenitors with the broadest developmental potential in a given tissue at a given\\u000a time. Normal stem cells in the adult organism are responsible for renewal and repair of aged or damaged tissue. Adult stem\\u000a cells are present in virtually all tissues and during most stages of development. In this review, we introduce the reader\\u000a to

Sabine Hombach-Klonisch; Soumya Panigrahi; Anja Seifert; Esteban Alberti; Paola Pocar; Maciej Kurpisz; Klaus Schulze-Osthoff; Andrzej Mackiewicz; Marek Los

2008-01-01

312

A Sox2 distal enhancer cluster regulates embryonic stem cell differentiation potential.  

PubMed

The Sox2 transcription factor must be robustly transcribed in embryonic stem (ES) cells to maintain pluripotency. Two gene-proximal enhancers, Sox2 regulatory region 1 (SRR1) and SRR2, display activity in reporter assays, but deleting SRR1 has no effect on pluripotency. We identified and functionally validated the sequences required for Sox2 transcription based on a computational model that predicted transcriptional enhancer elements within 130 kb of Sox2. Our reporter assays revealed three novel enhancers--SRR18, SRR107, and SRR111--that, through the formation of chromatin loops, form a chromatin complex with the Sox2 promoter in ES cells. Using the CRISPR/Cas9 system and F1 ES cells (Mus musculus(129) × Mus castaneus), we generated heterozygous deletions of each enhancer region, revealing that only the distal cluster containing SRR107 and SRR111, located >100 kb downstream from Sox2, is required for cis-regulation of Sox2 in ES cells. Furthermore, homozygous deletion of this distal Sox2 control region (SCR) caused significant reduction in Sox2 mRNA and protein levels, loss of ES cell colony morphology, genome-wide changes in gene expression, and impaired neuroectodermal formation upon spontaneous differentiation to embryoid bodies. Together, these data identify a distal control region essential for Sox2 transcription in ES cells. PMID:25512558

Zhou, Harry Y; Katsman, Yulia; Dhaliwal, Navroop K; Davidson, Scott; Macpherson, Neil N; Sakthidevi, Moorthy; Collura, Felicia; Mitchell, Jennifer A

2014-12-15

313

Transthyretin as a potential biomarker for the differential diagnosis between lung cancer and lung infection  

PubMed Central

Satisfactory biomarkers for screening and early diagnosis of lung cancer remain scarce and require further investigation. The aim of the present study was to examine the changes of the biochemical and protein composition in the serum and pleural effusion from lung cancer and lung infection (bacterial pneumonia) patients. A total of 92 patients with lung cancer, 38 with bacterial pneumonia and 42 healthy controls were enrolled in the study. The serum levels of cholesterol, apolipoprotein A and transthyretin (TTR) in the lung cancer patients were higher than that of the lung infection patients (P<0.05). The levels of TTR were higher, whereas the activity of adenosine deaminase (ADA) was lower in the pleural effusion from the lung cancer patients compared to the lung infection patients (P<0.05). Furthermore, the pleural effusion/serum TTR ratios in the lung cancer patients were higher, whereas the ratios of ADA were lower (P<0.05). By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, four major peaks corresponding to native TTR, Sul-TTR, Cys-TTR and Cysgly-TTR were observed in the serum of the lung cancer and lung infection patients. A significant increase was found in the proportion of Cysgly-TTR in the pleural effusion from the patients with lung cancer. The data indicated that a combination of pleural effusion/serum TTR ratios and modified TTR may be beneficial for the differential diagnosis between lung cancer and lung infection. PMID:25054025

DING, HONGMEI; LIU, JIANHUA; XUE, RONG; ZHAO, PENG; QIN, YI; ZHENG, FANG; SUN, XUGUO

2014-01-01

314

Reduced numbers of switched memory B cells with high terminal differentiation potential in Down syndrome.  

PubMed

Children with Down syndrome (DS) have increased susceptibility to infections and a high frequency of leukemia and autoimmune disorders, suggesting that immunodeficiency and immune dysfunction are integral parts of the syndrome. A reduction in B-cell numbers has been reported, associated with moderate immunodeficiency and normal immunoglobulin levels. Here, we compared B-cell populations of 19 children with DS with those in healthy age-matched controls. We found that all steps of peripheral B-cell development are altered in DS, with a more severe defect during the later stages of B-cell development. Transitional and mature-naïve B-cell numbers are reduced by 50% whereas switched memory B cells represent 10-15% of the numbers in age-matched controls. Serum IgM levels were slightly reduced, but all other immunoglobulin isotypes were in the normal range. The frequency of switched memory B cells specific for vaccine antigens was significantly lower in affected children than in their equivalently vaccinated siblings. In vitro switched memory B cells of patients with DS have an increased ability to differentiate into antibody-forming cells in response to TLR9 signals. Tailored vaccination schedules increasing the number of switched memory B cells may improve protection and reduce the risk of death from infection in DS. PMID:25472482

Carsetti, Rita; Valentini, Diletta; Marcellini, Valentina; Scarsella, Marco; Marasco, Emiliano; Giustini, Ferruccio; Bartuli, Andrea; Villani, Alberto; Ugazio, Alberto G

2015-03-01

315

The plasticity and potential of leukemia cell lines to differentiate into dendritic cells  

PubMed Central

Dendritic cells (DCs) are potent antigen-presenting cells that orchestrate the innate and adaptive immune systems to induce immunity. DCs are significant in maintaining immune tolerance towards self-antigens, organ transplantation and allergic responses. DCs are powerful adjuvants for eliciting T-cell immunity and are therefore considered primary targets for inducing immune responses in the prevention and treatment of infectious diseases and cancer. DCs have been increasingly applied in the immunotherapy of cancer worldwide during the last decade; however, a number of the highly specialized biological characteristics of DCs remain to be elucidated. Previous studies of human DCs have been constrained by certain difficulties, therefore the majority of studies have been carried out using in vitro model systems. Suitable cell lines with dendritic-like properties may provide valuable tools for the study of DC physiology and pathology. In the current review, various human DC line differentiation models are discussed. Certain cell lines provide valuable tools for studying the specific aspects of DC biology, despite variations in cell biological and immunological features when compared with primary DCs. PMID:23226789

GUO, QINGWEI; ZHANG, LELING; LI, FU; JIANG, GUOSHENG

2012-01-01

316

SUMOylation of ATRIP potentiates DNA damage signaling by boosting multiple protein interactions in the ATR pathway  

PubMed Central

The ATR (ATM [ataxia telangiectasia-mutated]- and Rad3-related) checkpoint is a crucial DNA damage signaling pathway. While the ATR pathway is known to transmit DNA damage signals through the ATR–Chk1 kinase cascade, whether post-translational modifications other than phosphorylation are important for this pathway remains largely unknown. Here, we show that protein SUMOylation plays a key role in the ATR pathway. ATRIP, the regulatory partner of ATR, is modified by SUMO2/3 at K234 and K289. An ATRIP mutant lacking the SUMOylation sites fails to localize to DNA damage and support ATR activation efficiently. Surprisingly, the ATRIP SUMOylation mutant is compromised in the interaction with a protein group, rather than a single protein, in the ATR pathway. Multiple ATRIP-interacting proteins, including ATR, RPA70, TopBP1, and the MRE11–RAD50–NBS1 complex, exhibit reduced binding to the ATRIP SUMOylation mutant in cells and display affinity for SUMO2 chains in vitro, suggesting that they bind not only ATRIP but also SUMO. Fusion of a SUMO2 chain to the ATRIP SUMOylation mutant enhances its interaction with the protein group and partially suppresses its localization and functional defects, revealing that ATRIP SUMOylation promotes ATR activation by providing a unique type of protein glue that boosts multiple protein interactions along the ATR pathway. PMID:24990965

Wu, Ching-Shyi; Ouyang, Jian; Mori, Eiichiro; Nguyen, Hai Dang; Maréchal, Alexandre; Hallet, Alexander; Chen, David J.; Zou, Lee

2014-01-01

317

Detection of multiple potentially pathogenic bacteria in Matang mangrove estuaries, Malaysia.  

PubMed

The deltaic estuarine system of the Matang Mangrove Forest Reserve of Malaysia is a site where several human settlements and brackish water aquaculture have been established. Here, we evaluated the level of fecal indicator bacteria (FIB) and the presence of potentially pathogenic bacteria in the surface water and sediments. Higher levels of FIB were detected at downstream sampling sites from the fishing village, indicating it as a possible source of anthropogenic pollution to the estuary. Enterococci levels in the estuarine sediments were higher than in the surface water, while total coliforms and E. coli in the estuarine sediments were not detected in all samples. Also, various types of potentially pathogenic bacteria, including Klebsiella pneumoniae, Serratia marcescens and Enterobacter cloacae were isolated. The results indicate that the Matang estuarine system is contaminated with various types of potential human bacterial pathogens which might pose a health risk to the public. PMID:24820641

Ghaderpour, Aziz; Mohd Nasori, Khairul Nazrin; Chew, Li Lee; Chong, Ving Ching; Thong, Kwai Lin; Chai, Lay Ching

2014-06-15

318

Multiple liquid-liquid critical points and density anomaly in core-softened potentials  

NASA Astrophysics Data System (ADS)

The relation between liquid-liquid phase transitions and waterlike density anomalies in core-softened potentials of fluids was investigated in an exactly solvable one-dimensional lattice model and in a three-dimensional fluid with a Fermi-like potential, the latter by molecular dynamics. Both systems were shown to present three liquid phases, two liquid-liquid phase transitions closely connected to two distinct regions of anomalous density increase. We propose that an oscillatory behavior observed on the thermal expansion coefficient as a function of pressure can be used as a signature of the connection between the liquid-liquid phase transition and density anomaly.

Barbosa, Marco Aurélio A.; Salcedo, Evy; Barbosa, Marcia C.

2013-03-01

319

Equine mesenchymal stem cells from bone marrow, adipose tissue and umbilical cord: immunophenotypic characterization and differentiation potential  

PubMed Central

Introduction Studies with mesenchymal stem cells (MSCs) are increasing due to their immunomodulatory, anti-inflammatory and tissue regenerative properties. However, there is still no agreement about the best source of equine MSCs for a bank for allogeneic therapy. The aim of this study was to evaluate the cell culture and immunophenotypic characteristics and differentiation potential of equine MSCs from bone marrow (BM-MSCs), adipose tissue (AT-MSCs) and umbilical cord (UC-MSCs) under identical in vitro conditions, to compare these sources for research or an allogeneic therapy cell bank. Methods The BM-MSCs, AT-MSCs and UC-MSCs were cultured and evaluated in vitro for their osteogenic, adipogenic and chondrogenic differentiation potential. Additionally, MSCs were assessed for CD105, CD44, CD34, CD90 and MHC-II markers by flow cytometry, and MHC-II was also assessed by immunocytochemistry. To interpret the flow cytometry results, statistical analysis was performed using ANOVA. Results The harvesting and culturing procedures of BM-MSCs, AT-MSCs and UC-MSCs were feasible, with an average cell growth until the third passage of 25 days for BM-MSCs, 15 days for AT-MSCs and 26 days for UC-MSCs. MSCs from all sources were able to differentiate into osteogenic (after 10 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs), adipogenic (after 8 days for BM-MSCs and AT-MSCs and 15 days for UC-MSCs) and chondrogenic (after 21 days for BM-MSCs, AT-MSCs and UC-MSCs) lineages. MSCs showed high expression of CD105, CD44 and CD90 and low or negative expression of CD34 and MHC-II. The MHC-II was not detected by immunocytochemistry techniques in any of the MSCs studied. Conclusions The BM, AT and UC are feasible sources for harvesting equine MSCs, and their immunophenotypic and multipotency characteristics attained minimal criteria for defining MSCs. Due to the low expression of MHC-II by MSCs, all of the sources could be used in clinical trials involving allogeneic therapy in horses. However, the BM-MSCs and AT-MSCs showed fastest ‘‘in vitro’’ differentiation and AT-MSCs showed highest cell growth until third passage. These findings suggest that BM and AT may be preferable for cell banking purposes. PMID:24559797

2014-01-01

320

Muscarinic Receptor Activity Has Multiple Effects on the Resting Membrane Potentials of CA1 Hippocampal Interneurons  

Microsoft Academic Search

Inhibitory interneurons appear to be an important target for the muscarinic actions of cholinergic inputs to the hippocampus. We investigated the effect of muscarinic receptor activity on the membrane potential (Vm ) and currents of rat hippocampal CA1 interneurons using whole-cell recording from visually identified CA1 interneurons. The predominant response observed was a muscarinic depolarization that was detected in interneurons

A. Rory McQuiston; Daniel V. Madison

1999-01-01

321

Differentiation and migration properties of human foetal umbilical cord perivascular cells: potential for lung repair  

PubMed Central

Abstract Mesenchymal stem cells (MSC) have been derived from different cultured human tissues, including bone marrow, adipose tissue, amniotic fluid and umbilical cord blood. Only recently it was suggested that MSC descended from perivascular cells, the latter being defined as CD146+ neuro-glial proteoglycan (NG)2+ platelet-derived growth factor-R?+ ALP+ CD34– CD45– von Willebrand factor (vWF)– CD144–. Herein we studied the properties of perivascular cells from a novel source, the foetal human umbilical cord (HUC) collected from pre-term newborns. By immunohistochemistry and flow cytometry we show that pre-term/foetal HUCs contain more perivascular cells than their full-term counterparts (2.5%versus 0.15%). Moreover, foetal HUC perivascular cells (HUCPC) express the embryonic cell markers specific embryonic antigen-4, Runx1 and Oct-4 and can be cultured over the long term. To further confirm the MSC identity of these cultured perivascular cells, we also showed their expression at different passages of antigens that typify MSC. The multilineage differentiative capacity of HUCPC into osteogenic, adipogenic and myogenic cell lineages was demonstrated in culture. In the perspective of a therapeutic application in chronic lung disease of pre-term newborns, we demonstrated the in vitro ability of HUCPC to migrate towards an alveolar type II cell line damaged with bleomycin, an anti-cancer agent with known pulmonary toxicity. The secretory profile exhibited by foetal HUCPC in the migration assay suggested a paracrine effect that could be exploited in various clinical conditions including lung disorders. PMID:20219017

Montemurro, Tiziana; Andriolo, Gabriella; Montelatici, Elisa; Weissmann, Gaia; Crisan, Mihaela; Colnaghi, Maria Rosa; Rebulla, Paolo; Mosca, Fabio; Péault, Bruno; Lazzari, Lorenza

2011-01-01

322

Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic.  

PubMed

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-?, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-?. In a mouse model of MS, experimental autoimmune encephalomyelitis, guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS CD4+ T cell accumulation. Moreover, guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment. PMID:25766071

Way, Sharon W; Podojil, Joseph R; Clayton, Benjamin L; Zaremba, Anita; Collins, Tassie L; Kunjamma, Rejani B; Robinson, Andrew P; Brugarolas, Pedro; Miller, Robert H; Miller, Stephen D; Popko, Brian

2015-01-01

323

Pharmaceutical integrated stress response enhancement protects oligodendrocytes and provides a potential multiple sclerosis therapeutic  

PubMed Central

Oligodendrocyte death contributes to the pathogenesis of the inflammatory demyelinating disease multiple sclerosis (MS). Nevertheless, current MS therapies are mainly immunomodulatory and have demonstrated limited ability to inhibit MS progression. Protection of oligodendrocytes is therefore a desirable strategy for alleviating disease. Here we demonstrate that enhancement of the integrated stress response using the FDA-approved drug guanabenz increases oligodendrocyte survival in culture and prevents hypomyelination in cerebellar explants in the presence of interferon-?, a pro-inflammatory cytokine implicated in MS pathogenesis. In vivo, guanabenz treatment protects against oligodendrocyte loss caused by CNS-specific expression of interferon-?. In a mouse model of MS, experimental autoimmune encephalomyelitis, guanabenz alleviates clinical symptoms, which correlates with increased oligodendrocyte survival and diminished CNS CD4+ T cell accumulation. Moreover, guanabenz ameliorates relapse in relapsing-remitting experimental autoimmune encephalomyelitis. Our results provide support for a MS therapy that enhances the integrated stress response to protect oligodendrocytes against the inflammatory CNS environment. PMID:25766071

Way, Sharon W.; Podojil, Joseph R.; Clayton, Benjamin L.; Zaremba, Anita; Collins, Tassie L.; Kunjamma, Rejani B.; Robinson, Andrew P.; Brugarolas, Pedro; Miller, Robert H.; Miller, Stephen D.; Popko, Brian

2015-01-01

324

Capacity to Make Medical Treatment Decisions in Multiple Sclerosis: A Potentially Remediable Deficit  

PubMed Central

Ability to make decisions about medical treatment is compromised in significant numbers of people with neurological and psychiatric illness, and this incapacity frequently corresponds with compromised neuropsychological function. Although cognitive deficits occur often in people with multiple sclerosis (MS), no research has studied decisional capacity in that disease. The present investigation examined ability to understand treatment disclosures, which is a core component of decisional capacity, in 36 people with MS and 16 normal controls. MS patients with diminished neuropsychological function showed poor understanding of treatment disclosures compared to the control group, and diminished new-learning and executive function correlated with poorer understanding. Nonetheless, with sufficient cueing, the MS patients with diminished neuropsychological function were able to display understanding that was equivalent to the control group. Implications of these results for clinical practice and medical research involving people with MS are discussed. PMID:20446143

Basso, Michael R.; Candilis, Philip J.; Johnson, Jay; Ghormley, Courtney; Combs, Dennis R.; Ward, Taeh

2010-01-01

325

Proteomic Profiling in Multiple Sclerosis Clinical Courses Reveals Potential Biomarkers of Neurodegeneration  

PubMed Central

The aim of our project was to perform an exploratory analysis of the cerebrospinal fluid (CSF) proteomic profiles of Multiple Sclerosis (MS) patients, collected in different phases of their clinical course, in order to investigate the existence of peculiar profiles characterizing the different MS phenotypes. The study was carried out on 24 Clinically Isolated Syndrome (CIS), 16 Relapsing Remitting (RR) MS, 11 Progressive (Pr) MS patients. The CSF samples were analysed using the Matrix Assisted Laser Desorption Ionisation Time Of Flight (MALDI-TOF) mass spectrometer in linear mode geometry and in delayed extraction mode (m/z range: 1000–25000 Da). Peak lists were imported for normalization and statistical analysis. CSF data were correlated with demographic, clinical and MRI parameters. The evaluation of MALDI-TOF spectra revealed 348 peak signals with relative intensity ?1% in the study range. The peak intensity of the signals corresponding to Secretogranin II and Protein 7B2 were significantly upregulated in RRMS patients compared to PrMS (p<0.05), whereas the signals of Fibrinogen and Fibrinopeptide A were significantly downregulated in CIS compared to PrMS patients (p<0.04). Additionally, the intensity of the Tymosin ?4 peak was the only signal to be significantly discriminated between the CIS and RRMS patients (p?=?0.013). Although with caution due to the relatively small size of the study populations, and considering that not all the findings remained significant after adjustment for multiple comparisons, in our opinion this mass spectrometry evaluation confirms that this technique may provide useful and important information to improve our understanding of the complex pathogenesis of MS. PMID:25098164

Liguori, Maria; Qualtieri, Antonio; Tortorella, Carla; Direnzo, Vita; Bagalà, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

2014-01-01

326

Myeloma-derived Dickkopf-1 disrupts Wnt-regulated osteoprotegerin and RANKL production by osteoblasts: a potential mechanism underlying osteolytic bone lesions in multiple myeloma  

Microsoft Academic Search

Multiple myeloma (MM) is characterized by osteolytic bone lesions (OBL) that arise as a consequence of osteoblast inactivation and osteoclast activation adjacent to tumor foci within bone. Wnt signaling in osteoblasts regulates osteoclastogenesis through the differential activation and inactivation of Re- ceptor Activator of Nuclear factor Kappa B Ligand (RANKL) and osteoprotegerin (OPG), positive and negative regulators of oste- oclast

Ya-Wei Qiang; Yu Chen; Owen Stephens; Nathan Brown; Bangzheng Chen; Joshua Epstein; Bart Barlogie; John D. Shaughnessy Jr

2008-01-01

327

A generalized Grubbs-Beck test statistic for detecting multiple potentially influential low outliers in flood series  

NASA Astrophysics Data System (ADS)

The Grubbs-Beck test is recommended by the federal guidelines for detection of low outliers in flood flow frequency computation in the United States. This paper presents a generalization of the Grubbs-Beck test for normal data (similar to the Rosner (1983) test; see also Spencer and McCuen (1996)) that can provide a consistent standard for identifying multiple potentially influential low flows. In cases where low outliers have been identified, they can be represented as "less-than" values, and a frequency distribution can be developed using censored-data statistical techniques, such as the Expected Moments Algorithm. This approach can improve the fit of the right-hand tail of a frequency distribution and provide protection from lack-of-fit due to unimportant but potentially influential low flows (PILFs) in a flood series, thus making the flood frequency analysis procedure more robust.

Cohn, T. A.; England, J. F.; Berenbrock, C. E.; Mason, R. R.; Stedinger, J. R.; Lamontagne, J. R.

2013-08-01

328

A generalized Grubbs-Beck test statistic for detecting multiple potentially influential low outliers in flood series  

USGS Publications Warehouse

he Grubbs-Beck test is recommended by the federal guidelines for detection of low outliers in flood flow frequency computation in the United States. This paper presents a generalization of the Grubbs-Beck test for normal data (similar to the Rosner (1983) test; see also Spencer and McCuen (1996)) that can provide a consistent standard for identifying multiple potentially influential low flows. In cases where low outliers have been identified, they can be represented as “less-than” values, and a frequency distribution can be developed using censored-data statistical techniques, such as the Expected Moments Algorithm. This approach can improve the fit of the right-hand tail of a frequency distribution and provide protection from lack-of-fit due to unimportant but potentially influential low flows (PILFs) in a flood series, thus making the flood frequency analysis procedure more robust.

Cohn, T.A.; England, J.F.; Berenbrock, C.E.; Mason, R.R.; Stedinger, J.R.; Lamontagne, J.R.

2013-01-01

329

MiRNAs with Apoptosis Regulating Potential Are Differentially Expressed in Chronic Exercise-Induced Physiologically Hypertrophied Hearts  

PubMed Central

Physiological cardiac hypertrophy is an adaptive mechanism, induced during chronic exercise. As it is reversible and not associated with cardiomyocyte death, it is considered as a natural tactic to prevent cardiac dysfunction and failure. Though, different studies revealed the importance of microRNAs (miRNAs) in pathological hypertrophy, their role during physiological hypertrophy is largely unexplored. Hence, this study is aimed at revealing the global expression profile of miRNAs during physiological cardiac hypertrophy. Chronic swimming protocol continuously for eight weeks resulted in induction of physiological hypertrophy in rats and histopathology revealed the absence of tissue damage, apoptosis or fibrosis. Subsequently, the total RNA was isolated and small RNA sequencing was executed. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during physiological hypertrophy. The expression profile of the significantly differentially expressed miRNAs was validated by qPCR. In silico prediction of target genes by miRanda, miRdB and TargetScan and subsequent qPCR analysis unraveled that miRNAs including miR-99b, miR-100, miR-19b, miR-10, miR-208a, miR-133, miR-191a, miR-22, miR-30e and miR-181a are targeting the genes that primarily regulate cell proliferation and cell death. Gene ontology and pathway mapping showed that the differentially expressed miRNAs and their target genes were mapped to apoptosis and cell death pathways principally via PI3K/Akt/mTOR and MAPK signaling. In summary, our data indicates that regulation of these miRNAs with apoptosis regulating potential can be one of the major key factors in determining pathological or physiological hypertrophy by controlling fibrosis, apoptosis and cell death mechanisms. PMID:25793527

Ramprasath, Tharmarajan; Kalpana, Krishnan

2015-01-01

330

New Potential Ligand-Receptor Signaling Loops in Ovarian Cancer Identified in Multiple Gene Expression Studies  

Microsoft Academic Search

Based on the hypothesis that gene products involved in the same biological process would be coupled at transcriptional level, a previous study analyzed the correlation of the gene expression patterns of ligand-receptor (L-R) pairs to discover potential autocrine\\/paracrine signaling loops in different cancers (Graeber and Eisenberg. Nat Genet 2001; 29:295). By refining the starting database, a list of 511 L-R

Giancarlo Castellano; James F. Reid; Paola Alberti; Maria Luisa Carcangiu; Antonella Tomassetti; Silvana Canevari

331

Dynamics of ion transfer potentials at liquid-liquid interfaces: the case of multiple species.  

PubMed

The dynamic evolution of a water-nitrobenzene system with both solvents containing an initially equimolar mixture of two monovalent binary electrolytes, sharing a common cation, is simulated using the Nernst-Planck-Poisson finite difference method. The effect of single ion partition coefficients and diffusion coefficients on the evolution of potential across the liquid-liquid interface is investigated. Two separable components of the potential difference are observed: a static component localized at the liquid-liquid interface and a diffuse component with dynamic spatial expansion. The former is shown through novel calculations to be dependent on an apparent partition coefficient of the system, defined to be dependent on the partition coefficients of the two constituent salts such that the static component also depends on the single ion partition coefficient of the shared cation. The dynamic component depends on the same apparent partition coefficient; further, its dependence on the diffusion coefficients of the constituent ions is investigated, and the time scales of the potential difference formation are revealed. The evolution of the system can be described in three stages with short time behavior dominated by partition of ions and long-time behavior dominated by recovery of electroneutrality. The dynamics were correlated to those recently discussed for a simpler system [Zhurov, K. et al. J. Phys. Chem. B, 2011, 115, 6909-6921]. PMID:21936501

Zhurov, Konstantin; Dickinson, Edmund J F; Compton, Richard G

2011-11-01

332

Upregulation of miR-135b Is Involved in the Impaired Osteogenic Differentiation of Mesenchymal Stem Cells Derived from Multiple Myeloma Patients  

PubMed Central

Previous studies have demonstrated that mesenchymal stem cells from multiple myeloma (MM) patients (MM-hMSCs) display a distinctive gene expression profile, an enhanced production of cytokines and an impaired osteogenic differentiation ability compared to normal donors (ND-hMSCs). However, the underlying molecular mechanisms are unclear. In the present study, we observed that MM-hMSCs exhibited an abnormal upregulation of miR-135b, showing meanwhile an impaired osteogenic differentiation and a decrease of SMAD5 expression, which is the target of miR-135b involved in osteogenesis. By gain and loss of function studies we confirmed that miR-135b negatively regulated hMSCs osteogenesis. We also found that MM cell-produced factors stimulated ND-hMSCs to upregulate the expression of miR-135b. Importantly, treatment with a miR-135b inhibitor promoted osteogenic differentiation in MM-hMSCs. Finally, we observed that MM cell-derived soluble factors could induce an upregulation of miR-135b expression in ND-hMSCs in an indirect coculture system and the miR-135b expression turned to normal level after the removal of MM cells. Collectively, we provide evidence that miR-135b is involved in the impaired osteogenic differentiation of MSCs derived from MM patients and might therefore be a promising target for controlling bone disease. PMID:24223191

De Veirman, Kim; Vande Broek, Isabelle; Leleu, Xavier; De Becker, Ann; Van Camp, Ben; Vanderkerken, Karin; Van Riet, Ivan

2013-01-01

333

Differentiation potential of a basal epithelial cell line established from human bronchial explant.  

PubMed

Due to the cellular complexity of the airway epithelium, it is important to carefully define bronchial cell lines that capture the phenotypic traits of a particular cell type. We describe the characterization of a human bronchial epithelial cell line, VA10. It was established by transfection of primary bronchial epithelial cells with retroviral constructs containing the E6 and E7 oncogenes from HPV16. The cell line has been cultured for over 2 yr, a total of 60 passages. Although prolonged culture resulted in increased chromosomal instability, no major phenotypic drift in marker expression was observed. The cells expressed cytokeratins 5, 13, 14, and 17 suggesting a basal-like phenotype. This was further supported by the expression of alpha6beta4 integrins and the basal cell-associated transcription factor p63. The VA10 cell line generated high transepithelial electrical resistance in suspended and air-liquid interface culture, indicating functionally active tight junction (TJ) complexes. Immunocytochemistry showed the typical reticular structures of occludin and TJ-associated F-actin. VA10 produced pseudostratified layer in air-liquid interface culture with expression of p63 restricted to the basal layer. Furthermore, VA10 produced round colonies when cultured in laminin-rich reconstituted basement membrane, and immunostaining of claudin-1 and the basolateral marker beta4 integrin revealed colonies that generated polarization as expected in vivo. These data indicate that VA10 epithelia have the potential to model the bronchial epithelium in vivo and may be useful to study epithelial regeneration and repair and the effect of chemicals and potential drug candidates on TJ molecules in airway epithelia. PMID:17876679

Halldorsson, Skarphedinn; Asgrimsson, Valthor; Axelsson, Ivar; Gudmundsson, Gudmundur Hrafn; Steinarsdottir, Margret; Baldursson, Olafur; Gudjonsson, Thorarinn

2007-01-01

334

Contribution of Vestibular-Evoked Myogenic Potential (VEMP) testing in the assessment and the differential diagnosis of otosclerosis  

PubMed Central

Background The aim of this prospective clinical study was to evaluate the clinical importance of Vestibular-Evoked Myogenic Potentials (VEMPs) in the assessment and differential diagnosis of otosclerosis and otologic diseases characterized by “pseudo-conductive” components. We also investigated the clinical appearance of balance disorders in patients with otosclerosis by correlating VEMP results with the findings of caloric testing and pure tone audiometry(PTA). Material/Methods Air-conducted(AC) 4-PTA, bone-conducted(BC) 4-PTA, air-bone Gap(ABG), AC, BC tone burst evoked VEMP, and calorics were measured preoperatively in 126 otosclerotic ears. Results The response rate of the AC-VEMPs and BC-VEMPs was 29.36% and 44.03%, respectively. Statistical differences were found between the means of ABG, AC 4-PTA, and BC 4-PTA in the otosclerotic ears in relation to AC-VEMP elicitability. About one-third of patients presented with disequilibrium. A statistically significant interaction was found between calorics and dizziness in relation to PTA thresholds. No relationship was found between calorics and dizziness with VEMPs responses. Conclusions AC and BC VEMPs can be elicited in ears with otosclerosis. AC-VEMP is more vulnerable to conductive hearing loss. Evaluation of AC-VEMP thresholds can be added in the diagnostic work-up of otosclerosis in case of doubt, enhancing differential diagnosis in patients with air-bone gaps. Otosclerosis is not a cause of canal paresis or vertigo. PMID:24509900

Tramontani, Ourania; Gkoritsa, Eleni; Ferekidis, Eleftherios; Korres, Stavros G.

2014-01-01

335

Following a tick bite: double infections by tick-borne encephalitis virus and the spirochete Borrelia and other potential multiple infections.  

PubMed

In Central Europe and large parts of Asia, tick-borne-encephalitis (TBE) and Lyme borreliosis caused by the spirochetal bacterium of the genus Borrelia are among the most common diseases transmitted by the bite of a tick. When in regions with overlapping TBE virus and Borrelia endemicity, a tick bite causes the victim to become ill, it is important that appropriate serological and other laboratory investigations form part of the differential diagnosis. Account must always be taken of the fact that a tick bite may be followed by a double infection with the TBE virus and Borrelia. For this reason, a comprehensive diagnostic work-up aimed at detecting co-infection by both pathogens, even when the tick bite occurs in an endemic region for both pathogens but the initial clinical symptoms suggest an infection with only one of the two pathogens. The present article discusses a number of published cases of a co-infection with TBE virus and Borrelia and other potential multiple infections. PMID:21848518

Bröker, M

2012-05-01

336

Embryonic Stem Cells Derived from In Vivo or In Vitro-Generated Murine Blastocysts Display Similar Transcriptome and Differentiation Potential  

PubMed Central

The use of assisted reproductive technologies (ART) such as in vitro fertilization (IVF) has resulted in the birth of more than 5 million children. While children conceived by these technologies are generally healthy, there is conflicting evidence suggesting an increase in adult-onset complications like glucose intolerance and high blood pressure in IVF children. Animal models indicate similar potential risks. It remains unclear what molecular mechanisms may be operating during in vitro culture to predispose the embryo to these diseases. One of the limitations faced by investigators is the paucity of the material in the preimplantation embryo to test for molecular analysis. To address this problem, we generated mouse embryonic stem cells (mESC) from blastocysts conceived after natural mating (mESCFB) or after IVF, using optimal (KSOM + 5% O2; mESCKAA) and suboptimal (Whitten’s Medium, + 20% O2, mESCWM) conditions. All three groups of embryos showed similar behavior during both derivation and differentiation into their respective mESC lines. Unsupervised hierarchical clustering of microarray data showed that blastocyst culture does not affect the transcriptome of derived mESCs. Transcriptomic changes previously observed in the inner cell mass (ICM) of embryos derived in the same conditions were not present in mESCs, regardless of method of conception or culture medium, suggesting that mESC do not fully maintain a memory of the events occurring prior to their derivation. We conclude that the fertilization method or culture media used to generate blastocysts does not affect differentiation potential, morphology and transcriptome of mESCs. PMID:25723476

Simbulan, Rhodel K.; Di Santo, Marlea; Liu, Xiaowei; Lin, Wingka; Donjacour, Annemarie; Maltepe, Emin; Shenoy, Archana; Borini, Andrea; Rinaudo, Paolo

2015-01-01

337

Identification of Potential Tumor Differentiation Factor (TDF) Receptor from Steroid-responsive and Steroid-resistant Breast Cancer Cells*  

PubMed Central

Tumor differentiation factor (TDF) is a recently discovered protein, produced by the pituitary gland and secreted into the bloodstream. TDF and TDF-P1, a 20-amino acid peptide selected from the open reading frame of TDF, induce differentiation in human breast and prostate cancer cells but not in other cells. TDF protein has no identified site of action or receptor, and its mechanism of action is unknown. Here, we used TDF-P1 to purify and identify potential TDF receptor (TDF-R) candidates from MCF7 steroid-responsive breast cancer cells and non-breast HeLa cancerous cells using affinity purification chromatography (AP), and mass spectrometry (MS). We identified four candidate proteins from the 70-kDa heat shock protein (HSP70) family in MCF7 cells. Experiments in non-breast HeLa cancerous cells did not identify any TDF-R candidates. AP and MS experiments were validated by AP and Western blotting (WB). We additionally looked for TDF-R in steroid-resistant BT-549 cells and human dermal fibroblasts (HDF-a) using AP and WB. TDF-P1 interacts with potential TDF-R candidates from MCF7 and BT-549 breast cells but not from HeLa or HDF-a cells. Immunofluorescence (IF) experiments identified GRP78, a TDF-R candidate, at the cell surface of MCF7, BT-549 breast cells, and HeLa cells but not HDF-a cells. IF of other HSP70 proteins demonstrated labeling on all four cell types. These results point toward GRP78 and HSP70 proteins as strong TDF-R candidates and suggest that TDF interacts with its receptor, exclusively on breast cells, through a steroid-independent pathway. PMID:22130669

Sokolowska, Izabela; Woods, Alisa G.; Gawinowicz, Mary Ann; Roy, Urmi; Darie, Costel C.

2012-01-01

338

Is T-bet a potential therapeutic target in multiple sclerosis?  

PubMed

Treatments for multiple sclerosis (MS) have changed over the past years as our understanding of immunology and neuroscience has evolved. Experimental autoimmune encephalomyelitis (EAE) continues to remain the major model for MS and has been a major vehicle in the development of new therapeutic targets for MS, including new agents such as natalizumab, fingolimod, and dimethyl fumarate. As progress in the molecular understanding of immunology continues, many observations in EAE are pursued with the ultimate goal of defining the pathophysiology of MS and development of innovative treatments for the disease. Although many consider MS to be a T cell-mediated autoimmune disease directed against myelin antigens, the exact cause of the disease is still unknown. For many years, it was thought that myelin-specific T cells that secreted interferon-? and were proinflammatory were the major T cell subset that mediated the disease, but recent studies on the cytokine phenotype of pathogenic T cells in EAE and MS have opened debate on this issue. Work over the past several years suggests that the transcription factor T-bet appears to be an important factor in T cell encephalitogenicity; however, recent data suggest that it is also dispensable in certain situations, particularly for Th17 cells. Understanding the molecular mechanisms responsible for T cell encephalitogenicity in MS and other autoimmune diseases will be essential in the development of specific therapies for these inflammatory diseases. PMID:25084179

Racke, Michael K; Yang, Yuhong; Lovett-Racke, Amy E

2014-08-01

339

Polariton-polariton interaction potentials determination by pump-probe degenerate scattering in a multiple microcavity  

NASA Astrophysics Data System (ADS)

We study the polarization-dependent polariton-polariton interaction through its effect on a parametric scattering process in a microcavity (MC). The ratio of the anticircular interaction strength V2 over its cocircular counterpart V1 is involved in defining the regime in which many nonlinear processes arise in MCs, such as parametric conversion or condensation. We measure the ratio V2/V1 using a stimulated energy-degenerate parametric scattering process in a multiple MC. The sample is pumped at normal incidence, probed with a nonzero angle, and the phase-matched idler is observed at the opposite angle. The idler behavior, both in power and polarization, is compared to a Hamiltonian interaction model that takes into account the two polarization-dependent parametric scattering channels characterized by V1 and V2. The proposed method to measure the ratio V2/V1 is convenient and precise. The flexibility of the triple MC allows us to observe the process and measure this ratio over a large range of detunings, where we find it to be highly dependent on the detuning. These measurements complement the previous study of Vladimirova et al. [Phys. Rev. B 82, 075301 (2010), 10.1103/PhysRevB.82.075301] with an original approach and for detunings that were unexplored up to now.

Lecomte, Timothée; Taj, David; Lemaitre, Aristide; Bloch, Jacqueline; Delalande, Claude; Tignon, Jerome; Roussignol, Philippe

2014-04-01

340

Multiple ATP-hydrolyzing sites that potentially function in cytoplasmic dynein  

PubMed Central

Cytoplasmic dynein is a minus-end-directed microtubule motor involved in numerous essential processes within eukaryotic cells, such as nuclear segregation and trafficking of intracellular particles. The motor domain of the dynein heavy chain comprises six tandemly linked AAA (ATPase associated with diverse cellular activities) modules (AAA1–AAA6). The first four modules include nucleotide-binding sites (Walker A or P-loop motifs), and each of the four sites appears to bind ATP. However, the role and the function of each binding site are unknown. Especially, the question of which P-loops are ATP-hydrolyzing sites has not been answered, because it is difficult to measure the ATPase activity of each P-loop. Here, we purified several truncated Saccharomyces cerevisiae cytoplasmic dynein fragments and their mutants expressed in Escherichia coli and then measured their ATPase activities. Our results suggest that there are multiple ATP-binding sites that have abilities to hydrolyze ATP in cytoplasmic dynein. Furthermore, a single AAA module is insufficient for ATP hydrolysis, and the adjacent module facing the ATP-binding site is necessary for ATP-hydrolyzing activity. PMID:15326307

Takahashi, Yoshinori; Edamatsu, Masaki; Toyoshima, Yoko Y.

2004-01-01

341

Multiple ATP-hydrolyzing sites that potentially function in cytoplasmic dynein.  

PubMed

Cytoplasmic dynein is a minus-end-directed microtubule motor involved in numerous essential processes within eukaryotic cells, such as nuclear segregation and trafficking of intracellular particles. The motor domain of the dynein heavy chain comprises six tandemly linked AAA (ATPase associated with diverse cellular activities) modules (AAA1-AAA6). The first four modules include nucleotide-binding sites (Walker A or P-loop motifs), and each of the four sites appears to bind ATP. However, the role and the function of each binding site are unknown. Especially, the question of which P-loops are ATP-hydrolyzing sites has not been answered, because it is difficult to measure the ATPase activity of each P-loop. Here, we purified several truncated Saccharomyces cerevisiae cytoplasmic dynein fragments and their mutants expressed in Escherichia coli and then measured their ATPase activities. Our results suggest that there are multiple ATP-binding sites that have abilities to hydrolyze ATP in cytoplasmic dynein. Furthermore, a single AAA module is insufficient for ATP hydrolysis, and the adjacent module facing the ATP-binding site is necessary for ATP-hydrolyzing activity. PMID:15326307

Takahashi, Yoshinori; Edamatsu, Masaki; Toyoshima, Yoko Y

2004-08-31

342

The therapeutic potential of HDAC inhibitors in the treatment of multiple sclerosis.  

PubMed

Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) for which there is no efficacious cure. Thanks to numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been made available recently. Still, there is a terrible need for compounds capable of reducing the severity of the autoimmune attack and of blocking progression of the disorder. Also, besides the classic immunosuppressive strategies, it is now appreciated that compounds directly targeting neuronal death can be of relevance to the treatment of MS patients. Acetylation homeostasis is a key regulator of both immune cell activation and neuronal survival. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. In this review, we provide an appraisal of the literature on HDACi and MS, also discussing the mechanisms by which HDACi can suppress the autoimmune attack to the CNS. PMID:21373721

Faraco, Giuseppe; Cavone, Leonardo; Chiarugi, Alberto

2011-01-01

343

The Therapeutic Potential of HDAC Inhibitors in the Treatment of Multiple Sclerosis  

PubMed Central

Multiple sclerosis (MS) is a devastating autoimmune disorder of the central nervous system (CNS) for which there is no efficacious cure. Thanks to numerous preclinical and clinical studies, drugs able to mitigate the inexorable course of the disease have been made available recently. Still, there is a terrible need for compounds capable of reducing the severity of the autoimmune attack and of blocking progression of the disorder. Also, besides the classic immunosuppressive strategies, it is now appreciated that compounds directly targeting neuronal death can be of relevance to the treatment of MS patients. Acetylation homeostasis is a key regulator of both immune cell activation and neuronal survival. Of note, potent histone deacetylase inhibitors (HDACi) endowed with antiinflammatory and neuroprotective properties have been identified. Efficacy of HDACi in experimental models of MS has been reported consistently. In this review, we provide an appraisal of the literature on HDACi and MS, also discussing the mechanisms by which HDACi can suppress the autoimmune attack to the CNS. PMID:21373721

Faraco, Giuseppe; Cavone, Leonardo; Chiarugi, Alberto

2011-01-01

344

The potential role of iNKT cells in experimental allergic encephalitis and multiple sclerosis.  

PubMed

Multiple sclerosis (MS) is an autoimmune disorder associated with neurological signs and chronic inflammatory demyelination of the central nervous system (CNS). MS has been thought as Th1 (T helper) and Th17 cells mediated disease, but cells of the innate immune system play an important role both in the initiation and progression of MS. The invariant Natural Killer T (iNKT) cells are the unique innate lymphocytes subtype involved in inflammation and autoimmune disorders and secretes cytokines such as interferon gamma (IFN-?), Interleukin (IL)-10, IL-4 and IL-13. A reduction in number or defect in function of iNKT cells has been associated with an increased prevalence of autoimmune disorders indicating that iNKT cells have an immune-regulatory role in autoimmune disorders. Also, the protective role of iNKT cells has been extensively studied in EAE and the results of these studies show that iNKT cells might be a target for therapeutic purposes, but needs more extensive studies of their biology. In this review, we will attempt to show the protective role of iNKT cells in the pathogenesis of EAE and human disease. PMID:24601677

Roozbeh, Maryam; Mohammadpour, Hemn; Azizi, Gholamreza; Ghobadzadeh, Samira; Mirshafiey, Abbas

2014-04-01

345

Lipidome analysis in multiple sclerosis reveals protein lipoxidative damage as a potential pathogenic mechanism.  

PubMed

Metabolomic and lipidomic analyses have been used for the profiling of neurodegenerative processes, both in targeted and untargeted approaches. In this work we have applied these techniques to the study of CSF samples of multiple sclerosis (MS) patients (n = 9), compared with samples of non-MS individuals (n = 9) using mass-spectrometry. We have used western-blot and analyzed cell culture to confirm pathogenic pathways suggested by mass-spectrometric measurements. The results of the untargeted approach of metabolomics and lipidomics suggest the existence of several metabolites and lipids discriminating both populations. Applying targeted lipidomic analyses focused to a pathogenic pathway in MS, oxidative stress, reveal that the lipid peroxidation marker 8-iso-prostaglandin F2? is increased in CSF from MS patients. Furthermore, as lipid peroxidation exerts its pathogenical effects through protein modification, we studied the incidence of protein lipoxidation, revealing specific increases in carboxymethylated, neuroketal and malondialdehyde-mediated protein modifications in proteins of CSF from MS patients, despite the absence of their precursors glyoxal and methylglyoxal. Finally, we report that the level of neuroketal-modified proteins correlated with a hitherto unknown increased amount of autoantibodies against lipid peroxidation-modified proteins in CSF, without compensation by signaling induced by lipid peroxidation via peroxisome proliferator-activated receptor ? (PPAR?). The results, despite the limitation of being obtained in a small population, strongly suggest that autoimmunity against in situ produced epitopes derived from lipid peroxidation can be a relevant pathogenic factor in MS. PMID:22924648

Gonzalo, Hugo; Brieva, Luis; Tatzber, Franz; Jové, Mariona; Cacabelos, Daniel; Cassanyé, Anna; Lanau-Angulo, Lucia; Boada, Jordi; Serrano, José C E; González, Cristina; Hernández, Lourdes; Peralta, Sílvia; Pamplona, Reinald; Portero-Otin, Manuel

2012-11-01

346

Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation  

PubMed Central

Purpose The purpose of this study was to develop a framework for analyzing retinal pigment epithelium (RPE) expression profiles from zebrafish eye mutants. Methods The fish model we used was SWI/SNF-related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4 (smarca4), a retinal dystrophic mutant with a previously described retinal phenotype and expression profiles. Histological and Affymetrix GeneChip analyses were conducted to characterize the RPE defects and underlying differential expression, respectively. Results Histological analysis revealed that smarca4 RPE was formed, but its differentiation was abnormal. In particular, ultrastructural analysis of smarca4 RPE by transmission electron microscopy demonstrated several defects in melanogenesis. The nature of these defects also suggests that the cytoskeletal dynamics, which are tightly linked with melanogenesis, were impaired in smarca4 RPE. To compare the expression profile of normal wild-type (WT) and smarca4 RPE, the gene expression profiles of microdissected retinas and RPE-attached retinas were measured with Affymetrix GeneChip analysis. The RPE expression values were then estimated from these samples by subtracting the retinal expression values from the expression values of the RPE-attached retinas. A factorial analysis was conducted using the expression values of the RPE, retinal, and whole-embryo samples. Specific rules (contrasts) were built using the coefficients of the resulting fitted models to select for three groups of genes: 1) smarca4-regulated RPE genes, 2) smarca4-regulated retinal genes, and 3) smarca4-regulated RPE genes that are not differentially expressed in the retina. Interestingly, the third group consists of 39 genes that are highly related to cytoskeletal dynamics, melanogenesis, and paracrine and intracellular signal transduction. Conclusions Our analytical framework provides an experimental approach to identify differentially-regulated genes in the retina and the RPE of zebrafish mutants in which both of these tissues are affected by the underlying mutation. Specifically, we have used the method to identify a group of 39 genes that can potentially explain the melanogenesis defect in the smarca4 RPE. In addition, several genes in this group are secreted signaling molecules. Thus, this observation further implicates that the smarca4 RPE might play a role in the retinal dystrophic phenotype in smarca4. PMID:24426776

Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

2014-01-01

347

Preservation of Differentiation and Clonogenic Potential of Human Hematopoietic Stem and Progenitor Cells during Lyophilization and Ambient Storage  

PubMed Central

Progenitor cell therapies show great promise, but their potential for clinical applications requires improved storage and transportation. Desiccated cells stored at ambient temperature would provide economic and practical advantages over approaches employing cell freezing and subzero temperature storage. The objectives of this study were to assess a method for loading the stabilizing sugar, trehalose, into hematopoietic stem and progenitor cells (HPC) and to evaluate the effects of subsequent freeze-drying and storage at ambient temperature on differentiation and clonogenic potential. HPC were isolated from human umbilical cord blood and loaded with trehalose using an endogenous cell surface receptor, termed P2Z. Solution containing trehalose-loaded HPC was placed into vials, which were transferred to a tray freeze-dryer and removed during each step of the freeze-drying process to assess differentiation and clonogenic potential. Control groups for these experiments were freshly isolated HPC. Control cells formed 1450±230 CFU-GM, 430±140 BFU-E, and 50±40 CFU-GEMM per 50 µL. Compared to the values for the control cells, there was no statistical difference observed for cells removed at the end of the freezing step or at the end of primary drying. There was a gradual decrease in the number of CFU-GM and BFU-E for cells removed at different temperatures during secondary drying; however, there were no significant differences in the number of CFU-GEMM. To determine storage stability of lyophilized HPC, cells were stored for 4 weeks at 25°C in the dark. Cells reconstituted immediately after lyophilization produced 580±90 CFU-GM (?40%, relative to unprocessed controls p<0.0001), 170±70 BFU-E (?40%, p<0.0001), and 41±22 CFU-GEMM (?82%, p?=?0.4171), and cells reconstituted after 28 days at room temperature produced 513±170 CFU-GM (?35%, relative to unprocessed controls, p<0.0001), 112±68 BFU-E (?26%, p<0.0001), and 36±17 CFU-GEMM (?82%, p?=?0.2164) These studies are the first to document high level retention of CFU-GEMM following lyophilization and storage for 4 weeks at 25°C. This type of flexible storage stability would potentially permit the ability to ship and store HPC without the need for refrigeration. PMID:20824143

Buchanan, Sandhya S.; Pyatt, David W.; Carpenter, John F.

2010-01-01

348

Spontaneous emotion regulation: Differential effects on evoked brain potentials and facial muscle activity.  

PubMed

Late positive potentials (LPPs) were found to be decreased during down-regulation and increased during up-regulation of positive and negative emotions. However, previous studies lack ecological validity, since they explicitly instructed their participants to use certain regulation strategies. The goal of our study was to test an ecologically more valid paradigm of emotion regulation. We therefore investigated the effects of freely chosen emotion regulation strategies on LPPs and additionally assessed facial EMG responses and valence and arousal ratings as control variables. Responses to positive IAPS pictures were marked by pleasant valence ratings and high activations of M. zygomaticus major, negative pictures elicited unpleasant valence ratings and high activations of M. corrugator supercilii, and both, positive and negative pictures, went along with increased arousal ratings and LPPs. Importantly, ratings and EMG activity were intensified through up-regulation and attenuated through down-regulation of emotions, while LPPs were increased through both up-and down-regulation. We conclude that LPPs in paradigms with free choice of emotion regulation strategies might be a marker of attentional resources required for the selection of adequate emotion up- and down-regulation strategies, while LPP effects following emotion regulation with specific, instructed strategies reflect modulated arousal processes. PMID:25715271

Baur, Ramona; Conzelmann, Annette; Wieser, Matthias J; Pauli, Paul

2015-04-01

349

Triterpene saponosides from Lysimachia ciliata differentially attenuate invasive potential of prostate cancer cells.  

PubMed

Neither androgen ablation nor chemotherapeutic agents are effective in reducing the risk of prostate cancer progression. On the other hand, multifaceted effects of phytochemicals, such as triterpene saponins, on cancer cells have been suggested. A promising safety and tolerability profile indicate their possible application in the treatment of advanced prostate cancers. We analyzed the specificity, selectivity and versatility of desglucoanagalloside B effects on human prostate cancer cells derived from prostate cancer metastases to brain (DU-145 cells) and bone (PC-3 cells). Prominent growth arrest and apoptotic response of both cell types was observed in the presence of sub-micromolar desglucoanagalloside B concentrations. This was accompanied by cytochrome c release and caspase 3/7 activation. A relatively low cytostatic and pro-apoptotic response of cancer cells to a desglucoanagalloside B analog, anagallosaponin IV, illustrated the specificity of the effects of desglucoanagalloside B, whereas the low sensitivity of normal prostate PNT2 cells to desglucoanagalloside B showed the selectivity of its action. Inhibition of cancer cell motility was observed in the presence of both saponins, however only desglucoanagalloside B attenuated cancer cell invasive potential, predominantly through an effect on cell elastic properties. These data demonstrate the versatility of its effects on prostate cancer cells. In contrast to PNT2 cells, cancer cells tested in this study were relatively resistant to mitoxantrone. The multifaceted action of desglucoanagalloside B on basic cellular traits, crucial for prostate cancer progression, opens perspectives for elaboration of combined palliative therapies and new prostate cancer prophylaxis regimens. PMID:23954719

Koczurkiewicz, Paulina; Podolak, Irma; Skrzeczy?ska-Moncznik, Joanna; Sarna, Micha?; Wójcik, Katarzyna Anna; Ryszawy, Damian; Galanty, Agnieszka; Lasota, S?awomir; Madeja, Zbigniew; Czy?, Jaros?aw; Michalik, Marta

2013-10-25

350

Shrub Encroachment Impacts the Potential for Multiple Use Conflicts on Public Land  

NASA Astrophysics Data System (ADS)

Public rangelands in North America are typically managed under a multiple use policy that includes livestock grazing and wildlife management. In this article we report on the landscape level extent of grassland loss to shrub encroachment in a portion of the Rocky Mountain Forest Reserve in southwestern Alberta, Canada, and review the associated implications for simultaneously supporting livestock and wildlife populations while maintaining range health on this diminishing vegetation type. Digitized aerial photographs of 12 km of valley bottom from 1958 and 1974 were co-registered to ortho-rectified digital imagery taken in 1998, and an un-supervised classification used to determine areas associated with grassland and shrubland in each year. Field data from 2002 were over-layed using GPS coordinates to refine the classification using a calibration-validation procedure. Over the 40-year study period, open grasslands declined from 1,111 ha in 1958 to 465 ha in 1998, representing a 58% decrease. Using mean production data for grass and shrub dominated areas we then quantified aggregate changes in grazing capacity of both primary (grassland) and secondary (shrubland) habitats for livestock and wildlife. Total declines in grazing capacity from 1958 to 1998 totaled 2,744 Animal Unit Months (AUMs) of forage (-39%), including a 58% decrease in primary (i.e., open grassland) range, which was only partly offset by the availability of 1,357 AUMs within less productive and less accessible shrubland habitats. Our results indicate shrub encroachment has been extensive and significantly reduced forage availability to domestic livestock and wildlife, and will increase the difficulty of conserving remaining grasslands. Although current grazing capacities remain marginally above those specified by regulated grazing policies, it is clear that continued habitat change and decreases in forage availability are likely to threaten the condition of remaining grasslands. Unless shrub encroachment is arrested or grassland restoration initiated, reductions in aggregate ungulate numbers may be necessary.

Burkinshaw, Angela M.; Bork, Edward W.

2009-09-01

351

Clinicopathological significance and potential drug target of p15INK4B in multiple myeloma  

PubMed Central

Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. In addition to genetic changes, gene hypermethylation is an alternative mechanism of tumor suppressor gene inactivation in MM. The cyclin-dependent kinase inhibitor 1 (CDKN2B or p15INK4B) gene lies adjacent to the tumor suppressor gene, cyclin-dependent kinase inhibitor 2 (CDKN2A), and is frequently mutated and deleted in a wide variety of tumors, including MM. However, there is a lack of systematic analysis of p15 epigenetic modification such as methylation in MM from different studies that can provide more powerful estimation of an effect. In this study, we have systematically reviewed the studies of p15INK4B promoter methylation in MM and quantified the association between p15INK4B promoter methylation and MM using meta-analysis methods. We observed that the frequency of p15INK4B methylation is significantly higher in MM patients than in normal healthy controls. The pooled odds ratio (OR) from ten studies including 394 MM and 99 normal individuals is 0.08, while confidence interval (CI) is 0.03–0.21 (P<0.00001). This indicates that p15INK4B inactivation through methylation plays an important role in the pathogenesis of MM. In addition, the frequency of p15INK4B methylation was significantly higher in patients with MM than in those with asymptomatic monoclonal gammopathy of undetermined significance. The pooled OR from four studies is 0.40, 95% CI =0.21–0.78 (P=0.007). These results suggest that silencing of p15INK4B gene expression by epigenetic modification such as promoter hypermethylation plays a role not only in the initiation of MM but also in plasma cell malignant transformation, disease progression, and development. PMID:25382971

Li, Jun; Bi, Lintao; Lin, Yumei; Lu, Zhenxia; Hou, Gang

2014-01-01

352

Shrub encroachment impacts the potential for multiple use conflicts on public land.  

PubMed

Public rangelands in North America are typically managed under a multiple use policy that includes livestock grazing and wildlife management. In this article we report on the landscape level extent of grassland loss to shrub encroachment in a portion of the Rocky Mountain Forest Reserve in southwestern Alberta, Canada, and review the associated implications for simultaneously supporting livestock and wildlife populations while maintaining range health on this diminishing vegetation type. Digitized aerial photographs of 12 km of valley bottom from 1958 and 1974 were co-registered to ortho-rectified digital imagery taken in 1998, and an un-supervised classification used to determine areas associated with grassland and shrubland in each year. Field data from 2002 were over-layed using GPS coordinates to refine the classification using a calibration-validation procedure. Over the 40-year study period, open grasslands declined from 1,111 ha in 1958 to 465 ha in 1998, representing a 58% decrease. Using mean production data for grass and shrub dominated areas we then quantified aggregate changes in grazing capacity of both primary (grassland) and secondary (shrubland) habitats for livestock and wildlife. Total declines in grazing capacity from 1958 to 1998 totaled 2,744 Animal Unit Months (AUMs) of forage (-39%), including a 58% decrease in primary (i.e., open grassland) range, which was only partly offset by the availability of 1,357 AUMs within less productive and less accessible shrubland habitats. Our results indicate shrub encroachment has been extensive and significantly reduced forage availability to domestic livestock and wildlife, and will increase the difficulty of conserving remaining grasslands. Although current grazing capacities remain marginally above those specified by regulated grazing policies, it is clear that continued habitat change and decreases in forage availability are likely to threaten the condition of remaining grasslands. Unless shrub encroachment is arrested or grassland restoration initiated, reductions in aggregate ungulate numbers may be necessary. PMID:19588191

Burkinshaw, Angela M; Bork, Edward W

2009-09-01

353

Increases in intracellular calcium via activation of potentially multiple phospholipase C isozymes in mouse olfactory neurons  

PubMed Central

Phospholipase C (PLC) and internal Ca2+ stores are involved in a variety of cellular functions. However, our understanding of PLC in mammalian olfactory sensory neurons (OSNs) is generally limited to its controversial role in odor transduction. Here we employed single-cell Ca2+ imaging and molecular approaches to investigate PLC-mediated Ca2+ responses and its isozyme gene transcript expression. We found that the pan-PLC activator m-3M3FBS (25 ?M) induces intracellular Ca2+ increases in vast majority of isolated mouse OSNs tested. Both the response amplitude and percent responding cells depend on m-3M3FBS concentrations. In contrast, the inactive analog o-3M3FBS fails to induce Ca2+ responses. The m-3M3FBS-induced Ca2+ increase is blocked by the PLC inhibitor U73122, while its inactive analog U73433 has no effect. Removal of extracellular Ca2+ does not change significantly the m-3M3FBS-induced Ca2+ response amplitude. Additionally, in the absence of external Ca2+, we found that a subset of OSNs respond to an odorant mixture with small Ca2+ increases, which are significantly suppressed by U73122. Furthermore, using reverse transcription polymerase chain reaction and real-time quantitative polymerase chain reaction, we found that multiple PLC isozyme gene transcripts are expressed in olfactory turbinate tissue in various levels. Using RNA in situ hybridization analysis, we further show expression of ?4, ?1, ?2 gene transcripts in OSNs. Taken together, our results establish that PLC isozymes are potent enzymes for mobilizing intracellular Ca2+ in mouse OSNs and provide molecular insight for PLC isozymes-mediated complex cell signaling and regulation in the peripheral olfactory epithelium. PMID:25374507

Szebenyi, Steven A.; Ogura, Tatsuya; Sathyanesan, Aaron; AlMatrouk, Abdullah K.; Chang, Justin; Lin, Weihong

2014-01-01

354

Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy  

PubMed Central

Multiple sclerosis (MS) is a common chronic inflammatory demyelinating disease of the central nervous system (CNS) causing progressive disability. Many observations implicate Epstein–Barr virus (EBV) in the pathogenesis of MS, namely universal EBV seropositivity, high anti-EBV antibody levels, alterations in EBV-specific CD8+ T-cell immunity, increased spontaneous EBV-induced transformation of peripheral blood B cells, increased shedding of EBV from saliva and accumulation of EBV-infected B cells and plasma cells in the brain. Several mechanisms have been postulated to explain the role of EBV in the development of MS including cross-reactivity between EBV and CNS antigens, bystander damage to the CNS by EBV-specific CD8+ T cells, activation of innate immunity by EBV-encoded small RNA molecules in the CNS, expression of ?B-crystallin in EBV-infected B cells leading to a CD4+ T-cell response against oligodendrocyte-derived ?B-crystallin and EBV infection of autoreactive B cells, which produce pathogenic autoantibodies and provide costimulatory survival signals to autoreactive T cells in the CNS. The rapidly accumulating evidence for a pathogenic role of EBV in MS provides ground for optimism that it might be possible to prevent and cure MS by effectively controlling EBV infection through vaccination, antiviral drugs or treatment with EBV-specific cytotoxic CD8+ T cells. Adoptive immunotherapy with in vitro-expanded autologous EBV-specific CD8+ T cells directed against viral latent proteins was recently used to treat a patient with secondary progressive MS. Following the therapy, there was clinical improvement, decreased disease activity on magnetic resonance imaging and reduced intrathecal immunoglobulin production. PMID:25505955

Pender, Michael P; Burrows, Scott R

2014-01-01

355

Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis  

PubMed Central

Expression of PAX2 (Paired-box 2) is suppressed through promoter methylation at the later stages of embryonic development, but eventually reactivated during carcinogenesis. Pax-2 is commonly expressed in the most prevalent renal cell tumour (RCT) subtypes—clear cell RCC (ccRCC), papillary RCC (pRCC) and oncocytoma—but not in chromophobe RCC (chrRCC), which frequently displays chromosome 10 loss (to which PAX2 is mapped). Herein, we assessed the epigenetic and/or genetic alterations affecting PAX2 expression in RCTs and evaluated its potential as biomarker. We tested 120 RCTs (30 of each main subtype) and four normal kidney tissues. Pax-2 expression was assessed by immunohistochemistry and PAX2 mRNA expression levels were determined by quantitative RT-PCR. PAX2 promoter methylation status was assessed by methylation-specific PCR and bisulfite sequencing. Chromosome 10 and PAX2 copy number alterations were determined by FISH. Pax-2 immunoexpression was significantly lower in chrRCC compared to other RCT subtypes. Using a 10% immunoexpression cut-off, Pax-2 immunoreactivity discriminated chrRCC from oncocytoma with 67% sensitivity and 90% specificity. PAX2 mRNA expression was significantly lower in chrRCC, compared to ccRCC, pRCC and oncocytoma, and transcript levels correlated with immunoexpression. Whereas no promoter methylation was found in RCTs or normal kidney, 69% of chrRCC displayed chromosome 10 monosomy, correlating with Pax-2 immunoexpression. We concluded that Pax-2 expression might be used as an ancillary tool to discriminate chrRCC from oncocytomas with overlapping morphological features. The biological rationale lies on the causal relation between Pax-2 expression and chromosome 10 monosomy, but not PAX2 promoter methylation, in chrRCC. PMID:23890189

Patrício, Patrícia; Ramalho-Carvalho, João; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, João Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

2013-01-01

356

Differential Radiosensitizing Potential of Temozolomide in MGMT Promoter Methylated Glioblastoma Multiforme Cell Lines  

SciTech Connect

Purpose: To investigate the radiosensitizing potential of temozolomide (TMZ) for human glioblastoma multiforme (GBM) cell lines using single-dose and fractionated {gamma}-irradiation. Methods and Materials: Three genetically characterized human GBM cell lines (AMC-3046, VU-109, and VU-122) were exposed to various single (0-6 Gy) and daily fractionated doses (2 Gy per fraction) of {gamma}-irradiation. Repeated TMZ doses were given before and concurrent with irradiation treatment. Immediately plated clonogenic cell-survival curves were determined for both the single-dose and the fractionated irradiation experiments. To establish the net effect of clonogenic cell survival and cell proliferation, growth curves were determined, expressed as the number of surviving cells. Results: All three cell lines showed MGMT promoter methylation, lacked MGMT protein expression, and were sensitive to TMZ. The isotoxic TMZ concentrations used were in a clinically feasible range of 10 {mu}mol/L (AMC-3046), 3 {mu}mol/L (VU-109), and 2.5 {mu}mol/L (VU-122). Temozolomide was able to radiosensitize two cell lines (AMC 3046 and VU-122) using single-dose irradiation. A reduction in the number of surviving cells after treatment with the combination of TMZ and fractionated irradiation was seen in all three cell lines, but only AMC 3046 showed a radiosensitizing effect. Conclusions: This study on TMZ-sensitive GBM cell lines shows that TMZ can act as a radiosensitizer and is at least additive to {gamma}-irradiation. Enhancement of the radiation response by TMZ seems to be independent of the epigenetically silenced MGMT gen000.

Nifterik, Krista A. van [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Department of Neurogenetics, Academic Medical Center, Amsterdam (Netherlands); Berg, Jaap van den [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Stalpers, Lukas J.A. [Department of Radiotherapy, Academic Medical Center, Amsterdam (Netherlands); Lafleur, M. Vincent M. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Leenstra, Sieger [Department of Neurosurgery, Academic Medical Center, Amsterdam (Netherlands); Slotman, Ben J. [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands); Hulsebos, Theo J.M. [Department of Neurogenetics, Academic Medical Center, Amsterdam (Netherlands); Sminia, Peter [Department of Radiation Oncology, VU University Medical Center, Amsterdam (Netherlands)], E-mail: p.sminia@vumc.nl

2007-11-15

357

Comparative Analysis of Proliferation and Differentiation Potentials of Stem Cells from Inflamed Pulp of Deciduous Teeth and Stem Cells from Exfoliated Deciduous Teeth  

PubMed Central

Stem cells isolated from exfoliated deciduous teeth (SHEDs) are highly capable of proliferation and differentiation, and they represent good cell sources for mesenchymal stem cell- (MSC-) mediated dental tissue regeneration, but the supply of SHEDs is limited. A previous study found that stem cells could be isolated from inflamed tissues, but it is unknown whether primary dental pulp diagnosed with irreversible pulpitis might contain stem cells with appropriate tissue regeneration capacity. In this study, we aimed to isolate stem cells from both inflamed pulps of deciduous teeth (SCIDs) and SHEDs from Chinese children and to compare their proliferation and differentiation potentials. Our results showed that SCIDs were positive for cell surface markers, including CD105, CD90, and CD146, and they had high proliferation ability and osteogenic, adipogenic, and chondrogenic differentiation potentials. There was no significant difference in proliferation and differentiation potentials between SCIDs and SHEDs. The mRNA of inflammatory factors, including IL-1?, IL-6, and TNF-?, was expressed at similar levels in SCIDs and SHEDs, but SCIDs secreted more TNF-? protein. In conclusion, our in vitro results showed that SCIDs have proliferation and differentiation potentials similar to those of SHEDs. Thus, SCIDs represent a new potentially applicable source for MSC mediated tissue regeneration. PMID:25045714

Yu, Shi; Diao, Shu; Wang, Jinsong; Ding, Gang; Yang, Dongmei; Fan, Zhipeng

2014-01-01

358

Planetary surface dating from crater size-frequency distribution measurements: Multiple resurfacing episodes and differential isochron fitting  

NASA Astrophysics Data System (ADS)

The analysis of crater size-frequency distributions and absolute densities forms the basis of current approaches for estimating the absolute and relative ages of planetary surfaces. Users of the Neukum system of crater dating have conventionally used a cumulative presentation of the data, but because of the recent proliferation of interest in identifying resurfacing ages, it is worth emphasising the utility of the differential presentation of crater data in identifying resurfacing events and, particularly, in distinguishing the signature of short-lived events, such as volcanic flows, from long-acting processes, such as aeolian erosion. The work describes some additional considerations for making isochron fits to differentially plotted crater populations with respect to the removal of a binning bias for incrementally/differentially plotted data. The Hartmann approach has not typically employed the fitting of isochrons, but differential fitting would be a natural choice for this system, and is implemented in the Craterstats software. A revised calculation of the martian epoch boundary times in both chronology systems is provided.

Michael, G. G.

2013-09-01

359

Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of development  

Microsoft Academic Search

Signals of Notch transmembrane receptors function to regulate a wide variety of developmental cell fates. Here we investigate the role of Notch signaling in the development of mesodermal cell types by expressing a tamoxifen-inducible, activated form of Notch1 in embryonic stem cells (ESC). For differentiation of ESC into first mesodermal progenitor cells and then endothelial, mural, cardiac muscle and hematopoietic

Timm Schroeder; Franziska Meier-Stiegen; Ralf Schwanbeck; Hanna Eilken; Satomi Nishikawa; Robert Häsler; Stefan Schreiber; Georg W. Bornkamm; Shin-Ichi Nishikawa; Ursula Just

2006-01-01

360

Potential role of multiple carbon fixation pathways during lipid accumulation in Phaeodactylum tricornutum  

PubMed Central

Background Phaeodactylum tricornutum is a unicellular diatom in the class Bacillariophyceae. The full genome has been sequenced (<30?Mb), and approximately 20 to 30% triacylglyceride (TAG) accumulation on a dry cell basis has been reported under different growth conditions. To elucidate P. tricornutum gene expression profiles during nutrient-deprivation and lipid-accumulation, cell cultures were grown with a nitrate to phosphate ratio of 20:1 (N:P) and whole-genome transcripts were monitored over time via RNA-sequence determination. Results The specific Nile Red (NR) fluorescence (NR fluorescence per cell) increased over time; however, the increase in NR fluorescence was initiated before external nitrate was completely exhausted. Exogenous phosphate was depleted before nitrate, and these results indicated that the depletion of exogenous phosphate might be an early trigger for lipid accumulation that is magnified upon nitrate depletion. As expected, many of the genes associated with nitrate and phosphate utilization were up-expressed. The diatom-specific cyclins cyc7 and cyc10 were down-expressed during the nutrient-deplete state, and cyclin B1 was up-expressed during lipid-accumulation after growth cessation. While many of the genes associated with the C3 pathway for photosynthetic carbon reduction were not significantly altered, genes involved in a putative C4 pathway for photosynthetic carbon assimilation were up-expressed as the cells depleted nitrate, phosphate, and exogenous dissolved inorganic carbon (DIC) levels. P. tricornutum has multiple, putative carbonic anhydrases, but only two were significantly up-expressed (2-fold and 4-fold) at the last time point when exogenous DIC levels had increased after the cessation of growth. Alternative pathways that could utilize HCO3- were also suggested by the gene expression profiles (e.g., putative propionyl-CoA and methylmalonyl-CoA decarboxylases). Conclusions The results indicate that P. tricornutum continued carbon dioxide reduction when population growth was arrested and different carbon-concentrating mechanisms were used dependent upon exogenous DIC levels. Based upon overall low gene expression levels for fatty acid synthesis, the results also suggest that the build-up of precursors to the acetyl-CoA carboxylases may play a more significant role in TAG synthesis rather than the actual enzyme levels of acetyl-CoA carboxylases per se. The presented insights into the types and timing of cellular responses to inorganic carbon will help maximize photoautotrophic carbon flow to lipid accumulation. PMID:22672912

2012-01-01

361

A potential role for multiple tissue kallikrein serine proteases in epidermal desquamation.  

PubMed

Desquamation of the stratum corneum is a serine protease-dependent process. Two members of the human tissue kallikrein (KLK) family of (chymo)tryptic-like serine proteases, KLK5 and KLK7, are implicated in desquamation by digestion of (corneo)desmosomes and inhibition by desquamation-related serine protease inhibitors (SPIs). However, the epidermal localization and specificity of additional KLKs also supports a role for these enzymes in desquamation. This study aims to delineate the probable contribution of KLK1, KLK5, KLK6, KLK13, and KLK14 to desquamation by examining their interactions, in vitro, with: 1) colocalized SPI, lympho-epithelial Kazal-type-related inhibitor (LEKTI, four recombinant fragments containing inhibitory domains 1-6 (rLEKTI(1-6)), domains 6-8 and partial domain 9 (rLEKTI(6-9')), domains 9-12 (rLEKTI(9-12)), and domains 12-15 (rLEKTI(12-15)), secretory leukocyte protease inhibitor, and elafin and 2) their ability to digest the (corneo)desmosomal cadherin, desmoglein 1. KLK1 was not inhibited by any SPI tested. KLK5, KLK6, KLK13, and KLK14 were potently inhibited by rLEKTI(1-6), rLEKTI(6-9'), and rLEKTI(9-12) with Ki values in the range of 2.3-28.4 nm, 6.1-221 nm, and 2.7-416 nm for each respective fragment. Only KLK5 was inhibited by rLEKTI(12-15) (Ki = 21.8 nm). No KLK was inhibited by secretory leukocyte protease inhibitor or elafin. Apart from KLK13, all KLKs digested the ectodomain of desmoglein 1 within cadherin repeats, Ca2+ binding sites, or in the juxtamembrane region. Our study indicates that multiple KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI. These findings may have clinical implications for the treatment of skin disorders in which KLK activity is elevated. PMID:17158887

Borgoño, Carla A; Michael, Iacovos P; Komatsu, Nahoko; Jayakumar, Arumugam; Kapadia, Ravi; Clayman, Gary L; Sotiropoulou, Georgia; Diamandis, Eleftherios P

2007-02-01

362

Exercise body surface potential mapping in single and multiple coronary artery disease  

SciTech Connect

Body surface ST integral maps were recorded in 36 coronary artery disease (CAD) patients at: rest; peak, angina-limited exercise; and, 1 and 5 min of recovery. They were compared to maps of 15 CAD patients who exercised to fatigue, without angina, and eight normal subjects. Peak exercise heart rates were similar (NS) in all groups. With exercise angina, patients with two and three vessel CAD had significantly (p less than 0.05) greater decrease in the body surface sum of ST integral values than patients with single vessel CAD. CAD patients with exercise fatigue, in the absence of angina, had decreased ST integrals similar (NS) to patients with single vessel CAD who manifested angina and the normal control subjects. There was, however, considerable overlap among individuals; some patients with single vessel CAD had as much exercise ST integral decrease as patients with three vessel CAD. All CAD patients had persistent ST integral decreases at 5 min of recovery and there was a direct correlation of the recovery and peak exercise ST changes. Exercise ST changes correlated, as well, with quantitative CAD angiographic scores, but not with thallium perfusion scores. These data suggest exercise ST integral body surface mapping allows quantitation of myocardium at ischemic risk in patients with CAD, irrespective of the presence or absence of ischemic symptoms during exercise. A major potential application of this technique is selection of CAD therapy guided by quantitative assessment of ischemic myocardial risk.

Montague, T.J.; Witkowski, F.X.; Miller, R.M.; Johnstone, D.E.; MacKenzie, R.B.; Spencer, C.A.; Horacek, B.M. (Univ. of Alberta, Edmonton (Canada))

1990-06-01

363

Protective effects of bioactive phytochemicals from Mentha piperita with multiple health potentials.  

PubMed

Mentha piperita essential oil was bactericidal in order of E. coli> S. aureus > Pseudomonas aeruginosa > S. faecalis > Klebsiella pneumoniae. The oil with total phenolics of 89.43 ± 0.58 µg GAE/mg had 63.82 ± 0.05% DPPH inhibition activity with an IC (50) = 3.9 µg/ml. Lipid peroxidation inhibition was comparable to BHT and BHA. A 127% hike was noted in serum ferric-reducing antioxidant power. There was 38.3% decrease in WBCs count, while platelet count showed increased levels of 214.12%. Significant decrease in uric acid level and cholesterol/HDL and LDL/HDL ratios were recorded. The volatile oil displayed high cytotoxic action toward the human tumor cell line. The results of this study deserve attention with regard to antioxidative and possible anti-neoplastic chemotherapy that form a basis for future research. The essential oil of mint may be exploited as a natural source of bioactive phytopchemicals bearing antimicrobial and antioxidant potentials that could be supplemented for both nutritional purposes and preservation of foods. PMID:20931070

Sharafi, Seyedeh Maryam; Rasooli, Iraj; Owlia, Parviz; Taghizadeh, Massoud; Astaneh, Shakiba Darvish Alipoor

2010-07-01

364

Differential flatness-based trajectory planning for multiple unmanned aerial vehicles using mixed-integer linear programming  

Microsoft Academic Search

This paper provides a method for planning fuel-optimal trajectories for multiple unmanned aerial vehicles to reconfigure and traverse between goal points in a dynamic environment in real-time. Recent developments in robot motion planning have shown that trajectory optimization of linear vehicle systems including collision avoidance can be written as a linear program subject to mixed integer constraints, known as a

Yongxing Hao; A. Davari; A. Manesh

2005-01-01

365

Drug interaction potential of toremifene and N-desmethyltoremifene with multiple cytochrome P450 isoforms.  

PubMed

Toremifene is an effective agent for the treatment of breast cancer in postmenopausal women and is being evaluated for its ability to prevent bone fractures in men with prostate cancer taking androgen deprivation therapy. Due to the potential for drug-drug interactions, the ability of toremifene and its primary circulating metabolite N-desmethyltoremifene (NDMT) to inhibit nine human cytochrome P450 (CYP) enzymes was determined using human liver microsomes. Induction of CYP1A2 and 3A4 by toremifene was also investigated in human hepatocytes. Toremifene did not significantly inhibit CYP1A2 or 2D6. However, toremifene is a competitive inhibitor of CYP3A4, non-competitive inhibitor of CYP2A6, 2C8, 2C9, 2C19 and 2E1 and mixed-type inhibitor of CYP2B6. CYP inhibition by NDMT was similar in magnitude to toremifene. Toremifene did not induce CYP1A2 but increased CYP3A4 monooxygenase activity and gene expression in drug-exposed human primary hepatocytes. Although clinical doses of toremifene produce steady state exposures to toremifene and NDMT that may be sufficient to cause pharmacokinetic drug-drug interactions with other drugs metabolised by CYP2B6, CYP2C8, CYP3A4, CYP2C9 and CYP2C19, these data indicate that toremifene is unlikely to play a role in clinical drug-drug interactions with substrate drugs of CYP1A2 and CYP2D6. PMID:21726172

Kim, Juhyun; Peraire, Concepcion; Solà, Josep; Johanning, Karla M; Dalton, James T; Veverka, Karen A

2011-10-01

366

Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm  

PubMed Central

Background Recent declines in US cigarette smoking prevalence have coincided with increases in use of other tobacco products. Multiple product tobacco models can help assess the population health impacts associated with use of a wide range of tobacco products. Methods and Findings We present a multi-state, dynamical systems population structure model that can be used to assess the effects of tobacco product use behaviors on population health. The model incorporates transition behaviors, such as initiation, cessation, switching, and dual use, related to the use of multiple products. The model tracks product use prevalence and mortality attributable to tobacco use for the overall population and by sex and age group. The model can also be used to estimate differences in these outcomes between scenarios by varying input parameter values. We demonstrate model capabilities by projecting future cigarette smoking prevalence and smoking-attributable mortality and then simulating the effects of introduction of a hypothetical new lower-risk tobacco product under a variety of assumptions about product use. Sensitivity analyses were conducted to examine the range of population impacts that could occur due to differences in input values for product use and risk. We demonstrate that potential benefits from cigarette smokers switching to the lower-risk product can be offset over time through increased initiation of this product. Model results show that population health benefits are particularly sensitive to product risks and initiation, switching, and dual use behaviors. Conclusion Our model incorporates the variety of tobacco use behaviors and risks that occur with multiple products. As such, it can evaluate the population health impacts associated with the introduction of new tobacco products or policies that may result in product switching or dual use. Further model development will include refinement of data inputs for non-cigarette tobacco products and inclusion of health outcomes such as morbidity and disability. PMID:25815840

Vugrin, Eric D.; Rostron, Brian L.; Verzi, Stephen J.; Brodsky, Nancy S.; Brown, Theresa J.; Choiniere, Conrad J.; Coleman, Blair N.; Paredes, Antonio; Apelberg, Benjamin J.

2015-01-01

367

Differential metabolomic analysis of the potential antiproliferative mechanism of olive leaf extract on the JIMT-1 breast cancer cell line.  

PubMed

A new differential metabolomic approach has been developed to identify the phenolic cellular metabolites derived from breast cancer cells treated with a supercritical fluid extracted (SFE) olive leaf extract. The SFE extract was previously shown to have significant antiproliferative activity relative to several other olive leaf extracts examined in the same model. Upon SFE extract incubation of JIMT-1 human breast cancer cells, major metabolites were identified by using HPLC coupled to electrospray ionization quadrupole-time-of-flight mass spectrometry (ESI-Q-TOF-MS). After treatment, diosmetin was the most abundant intracellular metabolite, and it was accompanied by minor quantities of apigenin and luteolin. To identify the putative antiproliferative mechanism, the major metabolites and the complete extract were assayed for cell cycle, MAPK and PI3K proliferation pathways modulation. Incubation with only luteolin showed a significant effect in cell survival. Luteolin induced apoptosis, whereas the whole olive leaf extract incubation led to a significant cell cycle arrest at the G1 phase. The antiproliferative activity of both pure luteolin and olive leaf extract was mediated by the inactivation of the MAPK-proliferation pathway at the extracellular signal-related kinase (ERK1/2). However, the flavone concentration of the olive leaf extract did not fully explain the strong antiproliferative activity of the extract. Therefore, the effects of other compounds in the extract, probably at the membrane level, must be considered. The potential synergistic effects of the extract also deserve further attention. Our differential metabolomics approach identified the putative intracellular metabolites from a botanical extract that have antiproliferative effects, and this metabolomics approach can be expanded to other herbal extracts or pharmacological complex mixtures. PMID:25560707

Barrajón-Catalán, Enrique; Taamalli, Amani; Quirantes-Piné, Rosa; Roldan-Segura, Cristina; Arráez-Román, David; Segura-Carretero, Antonio; Micol, Vicente; Zarrouk, Mokhtar

2015-02-01

368

An Empirical Bayes Adjustment to Multiple p-values For the Detection of Differentially Expressed Genes in Microarray Experiments  

Microsoft Academic Search

In recent microarray experiments thousands of gene expressions are simultaneously tested in comparing samples (e.g., tissue types or experimental conditions). Application of a statistical test, such as the t-test, would lead to a p-value for each gene that reflects the amount of statistical evidence present in the data that the given gene is indeed differentially expressed. We show how to

Somnath Datta; Susmita Datta

2000-01-01

369

Knockdown of Human TCF4 Affects Multiple Signaling Pathways Involved in Cell Survival, Epithelial to Mesenchymal Transition and Neuronal Differentiation  

PubMed Central

Haploinsufficiency of TCF4 causes Pitt-Hopkins syndrome (PTHS): a severe form of mental retardation with phenotypic similarities to Angelman, Mowat-Wilson and Rett syndromes. Genome-wide association studies have also found that common variants in TCF4 are associated with an increased risk of schizophrenia. Although TCF4 is transcription factor, little is known about TCF4-regulated processes in the brain. In this study we used genome-wide expression profiling to determine the effects of acute TCF4 knockdown on gene expression in SH-SY5Y neuroblastoma cells. We identified 1204 gene expression changes (494 upregulated, 710 downregulated) in TCF4 knockdown cells. Pathway and enrichment analysis on the differentially expressed genes in TCF4-knockdown cells identified an over-representation of genes involved in TGF-? signaling, epithelial to mesenchymal transition (EMT) and apoptosis. Among the most significantly differentially expressed genes were the EMT regulators, SNAI2 and DEC1 and the proneural genes, NEUROG2 and ASCL1. Altered expression of several mental retardation genes such as UBE3A (Angelman Syndrome), ZEB2 (Mowat-Wilson Syndrome) and MEF2C was also found in TCF4-depleted cells. These data suggest that TCF4 regulates a number of convergent signaling pathways involved in cell differentiation and survival in addition to a subset of clinically important mental retardation genes. PMID:24058414

Forrest, Marc P.; Waite, Adrian J.; Martin-Rendon, Enca; Blake, Derek J.

2013-01-01

370

Activated Notch1 alters differentiation of embryonic stem cells into mesodermal cell lineages at multiple stages of development.  

PubMed

Signals of Notch transmembrane receptors function to regulate a wide variety of developmental cell fates. Here we investigate the role of Notch signaling in the development of mesodermal cell types by expressing a tamoxifen-inducible, activated form of Notch1 in embryonic stem cells (ESC). For differentiation of ESC into first mesodermal progenitor cells and then endothelial, mural, cardiac muscle and hematopoietic cells, the OP9 stroma co-culture system was used. Timed activation of Notch signaling by the addition of tamoxifen at various stages during differentiation of ESC into mesodermal cell lineages results in profound alterations in the generation of all of these cells. Differentiation of ESC into Flk1(+) mesodermal cells is inhibited by activated Notch. When Notch signaling is activated in mesodermal cells, generation of cardiac muscle, endothelial and hematopoietic cells is inhibited, favoring the generation of mural cells. Activation of Notch signaling in hematopoietic cells reduces colony formation and maintenance of hematopoiesis. These data suggest that Notch signaling plays a regulatory role in mesodermal development, cardiomyogenesis, the balanced generation of endothelial versus mural cells of blood vessels and hematopoietic development. PMID:16822655

Schroeder, Timm; Meier-Stiegen, Franziska; Schwanbeck, Ralf; Eilken, Hanna; Nishikawa, Satomi; Häsler, Robert; Schreiber, Stefan; Bornkamm, Georg W; Nishikawa, Shin-Ichi; Just, Ursula

2006-07-01

371

Differential expression of adenine nucleotide converting enzymes in mitochondrial intermembrane space: a potential role of adenylate kinase isozyme 2 in neutrophil differentiation.  

PubMed

Adenine nucleotide dynamics in the mitochondrial intermembrane space (IMS) play a key role in oxidative phosphorylation. In a previous study, Drosophila adenylate kinase isozyme 2 (Dak2) knockout was reported to cause developmental lethality at the larval stage in Drosophila melanogaster. In addition, two other studies reported that AK2 is a responsible gene for reticular dysgenesis (RD), a human disease that is characterized by severe combined immunodeficiency and deafness. Therefore, mitochondrial AK2 may play an important role in hematopoietic differentiation and ontogenesis. Three additional adenine nucleotide metabolizing enzymes, including mitochondrial creatine kinases (CKMT1 and CKMT2) and nucleoside diphosphate kinase isoform D (NDPK-D), have been found in IMS. Although these kinases generate ADP for ATP synthesis, their involvement in RD remains unclear and still an open question. In this study, mRNA and protein expressions of these mitochondrial kinases were firstly examined in mouse ES cells, day 8 embryos, and 7-week-old adult mice. It was found that their expressions are spatiotemporally regulated, and Ak2 is exclusively expressed in bone marrow, which is a major hematopoietic tissue in adults. In subsequent experiments, we identified increased expression of both AK2 and CKMT1 during macrophage differentiation and exclusive production of AK2 during neutrophil differentiation using HL-60 cells as an in vitro model of hematopoietic differentiation. Furthermore, AK2 knockdown specifically inhibited neutrophil differentiation without affecting macrophage differentiation. These data suggest that AK2 is indispensable for neutrophil differentiation and indicate a possible causative link between AK2 deficiency and neutropenia in RD. PMID:24587121

Tanimura, Ayako; Horiguchi, Taigo; Miyoshi, Keiko; Hagita, Hiroko; Noma, Takafumi

2014-01-01

372

Differential Expression of Adenine Nucleotide Converting Enzymes in Mitochondrial Intermembrane Space: A Potential Role of Adenylate Kinase Isozyme 2 in Neutrophil Differentiation  

PubMed Central

Adenine nucleotide dynamics in the mitochondrial intermembrane space (IMS) play a key role in oxidative phosphorylation. In a previous study, Drosophila adenylate kinase isozyme 2 (Dak2) knockout was reported to cause developmental lethality at the larval stage in Drosophila melanogaster. In addition, two other studies reported that AK2 is a responsible gene for reticular dysgenesis (RD), a human disease that is characterized by severe combined immunodeficiency and deafness. Therefore, mitochondrial AK2 may play an important role in hematopoietic differentiation and ontogenesis. Three additional adenine nucleotide metabolizing enzymes, including mitochondrial creatine kinases (CKMT1 and CKMT2) and nucleoside diphosphate kinase isoform D (NDPK-D), have been found in IMS. Although these kinases generate ADP for ATP synthesis, their involvement in RD remains unclear and still an open question. In this study, mRNA and protein expressions of these mitochondrial kinases were firstly examined in mouse ES cells, day 8 embryos, and 7-week-old adult mice. It was found that their expressions are spatiotemporally regulated, and Ak2 is exclusively expressed in bone marrow, which is a major hematopoietic tissue in adults. In subsequent experiments, we identified increased expression of both AK2 and CKMT1 during macrophage differentiation and exclusive production of AK2 during neutrophil differentiation using HL-60 cells as an in vitro model of hematopoietic differentiation. Furthermore, AK2 knockdown specifically inhibited neutrophil differentiation without affecting macrophage differentiation. These data suggest that AK2 is indispensable for neutrophil differentiation and indicate a possible causative link between AK2 deficiency and neutropenia in RD. PMID:24587121

Tanimura, Ayako; Horiguchi, Taigo; Miyoshi, Keiko; Hagita, Hiroko; Noma, Takafumi

2014-01-01

373

X-ray diffraction imaging with the Multiple Inverse Fan Beam topology: principles, performance and potential for security screening.  

PubMed

The steadily increasing number of explosive threat classes, including home-made explosives (HMEs), liquids, amorphous and gels (LAGs), is forcing up the false-alarm rates of security screening equipment. This development can best be countered by increasing the number of features available for classification. X-ray diffraction intrinsically offers multiple features for both solid and LAGs explosive detection, and is thus becoming increasingly important for false-alarm and cost reduction in both carry-on and checked baggage security screening. Following a brief introduction to X-ray diffraction imaging (XDI), which synthesizes in a single modality the image-forming and material-analysis capabilities of X-rays, the Multiple Inverse Fan Beam (MIFB) XDI topology is described. Physical relationships obtaining in such MIFB XDI components as the radiation source, collimators and room-temperature detectors are presented with experimental performances that have been achieved. Representative X-ray diffraction profiles of threat substances measured with a laboratory MIFB XDI system are displayed. The performance of Next-Generation (MIFB) XDI relative to that of the 2nd Generation XRD 3500TM screener (Morpho Detection Germany GmbH) is assessed. The potential of MIFB XDI, both for reducing the exorbitant cost of false alarms in hold baggage screening (HBS), as well as for combining "in situ" liquid and solid explosive detection in carry-on luggage screening is outlined. PMID:22245364

Harding, G; Fleckenstein, H; Kosciesza, D; Olesinski, S; Strecker, H; Theedt, T; Zienert, G

2012-07-01

374

Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.  

PubMed

A solid-phase humin, acting as an electron donor, was able to enhance multiple reductive biotransformations, including dechlorination of pentachlorophenol (PCP), dissimilatory reduction of amorphous Fe (III) oxide (FeOOH), and reduction of nitrate, in a consortium. Humin that was chemically reduced by NaBH4 served as an electron donor for these microbial reducing reactions, with electron donating capacities of 0.013 mmol e(-)/g for PCP dechlorination, 0.15 mmol e(-)/g for iron reduction, and 0.30 mmol e(-)/g for nitrate reduction. Two pairs of oxidation and reduction peaks within the humin were detected by cyclic voltammetry analysis. 16S rRNA gene sequencing-based microbial community analysis of the consortium incubated with different terminal electron acceptors, suggested that Dehalobacter sp., Bacteroides sp., and Sulfurospirillum sp. were involved in the PCP dechlorination, dissimilatory iron reduction, and nitrate reduction, respectively. These findings suggested that humin functioned as a versatile redox mediator, donating electrons for multiple respiration reactions with different redox potentials. PMID:25176636

Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

2015-02-01

375

Multiple stepwise pattern for potential of mean force in unfolding the thrombin binding aptamer in complex with Sr2+  

NASA Astrophysics Data System (ADS)

Using all-atom molecular dynamics simulation in conjunction with umbrella sampling, we obtained the unfolding free energy and the force extension profiles of the thrombin binding DNA aptamer (15-TBA) in complex with Sr2+ (Protein Data Bank code: 1RDE). The resulting potential of mean force (PMF) displays a multiple stepwise pattern with distinct plateau regions. The detailed analysis of the simulation result indicated that each plateau was created by the interplay of the metal ion interacting with self-arranging guanine bases and the successive uptakes of water molecules. The current PMF simulation provides a quantitative description of the unfolding process of 15-TBA DNA driven by stretching and gives molecular insight on its detailed changes of base pair interactions in the presence of the metal cation.

Yang, Changwon; Jang, Soonmin; Pak, Youngshang

2011-12-01

376

Microbial Monitoring of Pathogens by Comparing Multiple Real-Time PCR Platforms for Potential Space Applications  

NASA Technical Reports Server (NTRS)

The International Space Station (ISS) is a closed environment wih rotations of crew and equipment each introducing their own microbial flora making it necessary to monitor the air, surfaces, and water for microbial contamination. Current microbial monitoring includes labor and time intensive methods to enumerate total bacterial and fungal cells with limited characterization during in-flight testing. Although this culture-based method has been sufficient for monitoring the ISS, future long duration missions will need to perform more comprehensive characterization in-flight, since sample return and ground characterization may not be available. A workshop was held in 2011 at the Johnson Space Center to discuss alternative methodologies and technologies suitable for microbial monitoring for these longterm exploration missions where molecular-based methodologies, such as polymerase chain reaction (PCR), were recommended. In response, a multi-center (Marshall Space Flight Center, Johnson Space Center, Jet Propulsion Laboratory, and Kennedy Space Center) collaborative research effort was initiated to explore novel commercial-off-the-shelf hardware options for spaceflight environmental monitoring. The goal was to evaluate quantitative/semi-quantitative PCR approaches to space applications for low cost in-flight rapid identification of microorganisms affecting crew safety. The initial phase of this project identified commercially available platforms that could be minimally modified to perform nominally in microgravity followed by proof-of-concept testing on the highest qualifying candidates with a universally available test organism, Salmonella enterica. The platforms evaluated during proof-of-concept testing included the iCubate 2.0(TradeMark) (iCubate, Huntsville, AL), RAZOR EX (BioFire Diagnostics; Salt Lake City, Utah) and SmartCycler(TradeMark) (Cepheid; Sunnyvale, CA). The analysis identified two potential technologies (iCubate 2.0 and RAZOR EX) that were able to perform sample-to-answer testing with cell sample concentrations between SO to 400 cells. In addition, the commercial systems were evaluated for initial flight safety and readiness, sample concentration needs were reviewed, and a competitive procurement of commercially available platforms was initiated.

Birmele, Michele

2012-01-01

377

PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials.  

PubMed Central

A murine transcription factor, PEBP2, is composed of two subunits, alpha and beta. There are two genes in the mouse genome, PEBP2 alpha A and PEBP2 alpha B, which encode the alpha subunit. Two types of the alpha B cDNA clones, alpha B1 and alpha B2, were isolated from mouse fibroblasts and characterized. They were found to represent 3.8- and 7.9-kb transcripts, respectively. The 3.8-kb RNA encodes the previously described alpha B protein referred to as alpha B1, while the 7.9-kb RNA encodes a 387-amino-acid protein, termed alpha B2, which is identical to alpha B1 except that it has an internal deletion of 64 amino acid residues. Both alpha B1 and alpha B2 associate with PEBP2 beta and form a heterodimer. The alpha B2/beta complex binds to the PEBP2 binding site two- to threefold more strongly than the alpha B1/beta complex does. alpha B1 stimulates transcription through the PEBP2 site about 40-fold, while alpha B2 is only about 25 to 45% as active as alpha B1. Transactivation domain is located downstream of the 128-amino-acid runt homology region, referred to as the Runt domain. Mouse chromosome mapping studies revealed that alpha A, alpha B, and beta genes are mapped to chromosomes 17, 16, and 8, respectively. The last two genes are syntenic with the human AML1 on chromosome 21q22 and PEBP2 beta/CBF beta on 16q22 detected at the breakpoints of characteristic chromosome translocations of the two different subtypes of acute myeloid leukemia. These results suggest that previously described chimeric gene products, AML1/MTG8(ETO) and AML1-EAP generated by t(8;21) and t(3;21), respectively, lack the transactivation domain of AML1. Images PMID:8164679

Bae, S C; Ogawa, E; Maruyama, M; Oka, H; Satake, M; Shigesada, K; Jenkins, N A; Gilbert, D J; Copeland, N G; Ito, Y

1994-01-01

378

Design and fabrication of multiple-valued multiplexer using negative differential resistance circuits and standard SiGe process  

NASA Astrophysics Data System (ADS)

The design of a four-valued multiplexer using the negative differential resistance (NDR) circuit is demonstrated. The NDR circuit used in this work is made of the Si-based metal-oxide-semiconductor field-effect-transistor (MOS) and the SiGe-based heterojunction bipolar transistor (HBT). However we can obtain the NDR characteristic in its combined I- V curve by suitably arranging the MOS parameters. This novel multiplexer is made of MOS-HBT-NDR-based decoders and inverters. The fabrication is based on the standard 0.35 ?m SiGe BiCMOS process.

Gan, Kwang-Jow; Liang, Dong-Shong; Tsai, Cher-Shiung; Wen, Chun-Ming; Chen, Yaw-Hwang

2008-06-01

379

Carboxyl-terminal Domain of Transient Receptor Potential Vanilloid 1 Contains Distinct Segments Differentially Involved in Capsaicin- and Heat-induced Desensitization*  

PubMed Central

Multiple Ca2+-dependent processes are involved in capsaicin-induced desensitization of transient receptor potential vanilloid 1 (TRPV1), but desensitization of TRPV1 by heat occurs even in the absence of extracellular Ca2+, although the mechanisms are unknown. In this study, we tested the hypothesis that capsaicin and heat desensitize TRPV1 through distinct mechanisms involving distinct structural segments of TRPV1. In HEK293 cells that heterologously express TRPV1, we found that heat-induced desensitization was not affected by the inclusion of intracellular ATP or alanine mutation of Lys155, both of which attenuate capsaicin-induced desensitization, suggesting that heat-induced desensitization occurs through mechanisms distinct from capsaicin-induced desensitization. To determine protein domains involved in heat-induced desensitization, we generated chimeric proteins between TRPV1 and TRPV3, a heat-gated channel lacking heat-induced desensitization. We found that TRPV1 with the carboxyl-terminal domain (CTD) of TRPV3 retained heat activation but was impaired in heat-induced desensitization. Further experiments using chimeric or deletion mutants within TRPV1 CTD indicated that the distal half of CTD regulates the activation and desensitization of TRPV1 in modality-specific manners. Within the distal CTD, we identified two segments that distinctly regulated capsaicin- and heat-induced desensitization. The results suggest that the activation and desensitization of TRPV1 by capsaicin and heat can be modulated differentially and disproportionally through different regions of TRPV1 CTD. Identifying the domains involved in thermal regulation of TRPV1 may facilitate the development of novel anti-hyperalgesic approaches aimed at attenuating activation and enhancing desensitization of TRPV1 by thermal stimuli. PMID:24174527

Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y.; Chung, Man-Kyo

2013-01-01

380

Using Multiple Approaches, including ?18O Signatures of Phosphate to Investigate Potential Phosphorus Limitation and Cycling under Changing Climate Conditions  

NASA Astrophysics Data System (ADS)

Phosphorus (P) is often a limiting or co-limiting nutrient in terrestrial systems. It has been proposed that it will play an even greater role in ecosystems experiencing some of the many predicted effects of climate change, in particular release from nitrogen limitation. Recent work in 2007 by Menge et al. suggests that this is indeed a possibility. To investigate the potential for P limitation, and P cycling under multiple controlled conditions we collected samples from the Jasper Ridge Global Change Experiment (JRGCE) in May 2011. For over a decade the JRGCE has been manipulating four key parameters predicted to change in the future in a native Californian grassland system. Elevated Nitrogen deposition, increased precipitation, increased pCO2, and increased temperature are applied and monitored in a split plot design at the Jasper Ridge Biological Preserve in the eastern foothills of the Santa Cruz Mountains, California. Work done previously at the site using a suite of indicators of the potential P limitation suggest P limitation in some of the manipulated plots in the JRGCE. In this study we replicate a subset of the prior analyses to compare inter-annual signals of P limitation, and further attempt to utilize the oxygen isotopes of phosphate to investigate P cycling in soils at JRGCE. A fractional soil extraction process for phosphate enables separation of several operationally defined P pools, and provides auxiliary information regarding the relative concentrations of bio-available P, and relevant minerals in this grassland system under the varied conditions.

Roberts, K.; Paytan, A.; Field, C. B.; Honn, E.; Edwards, E.; Gottlieb, R.

2012-12-01

381

Differential sensitivity of osteoblasts and bacterial pathogens to 405-nm light highlighting potential for decontamination applications in orthopedic surgery  

NASA Astrophysics Data System (ADS)

Healthcare associated infections pose a major threat to patients admitted to hospitals and infection rates following orthopedic arthroplasty surgery are as high as 4%. A 405-nm high-intensity narrow spectrum light has been proven to reduce environmental contamination in hospital isolation rooms, and there is potential to develop this technology for application in arthroplasty surgery. Cultured rat osteoblasts were exposed to varying light intensities and it was found that exposures of up to a dose of 36 J/cm2 had no significant effect on cell viability [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay], function (alkaline phosphatase activity), and proliferation rate (BrdU cell proliferation assay). High irradiance exposures (54 J/cm2) significantly affected the cell viability indicating that the effects of 405-nm light on osteoblasts are dose dependent. Additionally, exposure of a variety of clinically related bacteria to a dose of 36 J/cm2 resulted in up to 100% kill. These results demonstrating the differential sensitivity of osteoblasts and bacteria to 405-nm light are an essential step toward developing the technique for decontamination in orthopedic surgery.

Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J.; Anderson, John G.; Grant, M. Helen

2014-10-01

382

Population Differentiation and Species Formation in the Deep Sea: The Potential Role of Environmental Gradients and Depth  

PubMed Central

Ecological speciation probably plays a more prominent role in diversification than previously thought, particularly in marine ecosystems where dispersal potential is great and where few obvious barriers to gene flow exist. This may be especially true in the deep sea where allopatric speciation seems insufficient to account for the rich and largely endemic fauna. Ecologically driven population differentiation and speciation are likely to be most prevalent along environmental gradients, such as those attending changes in depth. We quantified patterns of genetic variation along a depth gradient (1600-3800m) in the western North Atlantic for a protobranch bivalve (Nuculaatacellana) to test for population divergence. Multilocus analyses indicated a sharp discontinuity across a narrow depth range, with extremely low gene flow inferred between shallow and deep populations for thousands of generations. Phylogeographical discordance occurred between nuclear and mitochondrial loci as might be expected during the early stages of species formation. Because the geographic distance between divergent populations is small and no obvious dispersal barriers exist in this region, we suggest the divergence might reflect ecologically driven selection mediated by environmental correlates of the depth gradient. As inferred for numerous shallow-water species, environmental gradients that parallel changes in depth may play a key role in the genesis and adaptive radiation of the deep-water fauna. PMID:24098590

Jennings, Robert M.; Etter, Ron J.; Ficarra, Lynn

2013-01-01

383

Please cite this article in press as: M. Schiavon, et al., Transcriptome profiling of genes differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals a complex SCr interplay on sulfate transport regulati  

E-print Network

differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals differentially modulated by sulfur and chromium identifies potential targets for phytoremediation and reveals in the short-time response of plants to Cr exposure. I Potential gene targets for Cr phytoremediation have been

384

Integrative analysis of differential miRNA and functional study of miR-21 by seed-targeting inhibition in multiple myeloma cells in response to berberine  

PubMed Central

Background Berberine is a natural alkaloid derived from a traditional Chinese herbal medicine. It is known to modulate microRNA (miRNA) levels, although the mechanism for this action is unknown. Here, we previously demonstrate that the expression of 87 miRNAs is differentially affected by berberine in multiple myeloma cells. Among 49 miRNAs that are down-regulated, nine act as oncomirs, including miR-21. Integrative analysis showed that 28 of the down-regulated miRNAs participate in tumor protein p53 (TP53) signaling and other cancer pathways. miR-21 is involved in all these pathways, and is one of the most important oncomirs to be affected by berberine in multiple myeloma cells. Results We confirmed that berberine down-regulated miRNA-21 expression and significantly up-regulated the expression of programmed cell death 4 (PDCD4), a predicted miR-21 target. Luciferase reporter assays confirmed that PDCD4 was directly regulated by miR-21. Bioinformatic analysis revealed that the miR-21 promoter can be targeted by signal transducer and activator of transcription 3 (STAT3). Down-regulation of interleukin 6 (IL6) by berberine might lead to inhibition of miR-21 transcription through STAT3 down-regulation in multiple myeloma. Furthermore, both berberine and seed-targeting anti-miR-21 oligonucleotide induced apoptosis, G2-phase cell cycle arrest and colony inhibition in multiple myeloma cell lines. Depletion of PDCD4 by short interfering RNA could rescue berberine-induced cytotoxicity in multiple myeloma cells. Conclusions Our results suggest that berberine suppresses multiple myeloma cell growth, at least in part, by down-regulating miR-21 levels possibly through IL6/STAT3. This led to increased PDCD4 expression, which is likely to result in suppression of the p53 signaling pathway. These findings may also provide new mechanistic insight into the anti-cancer effects of certain compounds in traditional Chinese herbal medicines. PMID:25000828

2014-01-01

385

Multiple techniques for mineral identification on Mars:. a study of hydrothermal rocks as potential analogues for astrobiology sites on Mars  

NASA Astrophysics Data System (ADS)

Spectroscopic studies of Mars analog materials combining multiple spectral ranges and techniques are necessary in order to obtain ground truth information for interpretation of rocks and soils on Mars. Two hydrothermal rocks from Yellowstone National Park, Wyoming, were characterized here because they contain minerals requiring water for formation and they provide a possible niche for some of the earliest organisms on Earth. If related rocks formed in hydrothermal sites on Mars, identification of these would be important for understanding the geology of the planet and potential habitability for life. XRD, thermal properties, VNIR, mid-IR, and Raman spectroscopy were employed to identify the mineralogy of the samples in this study. The rocks studied here include a travertine from Mammoth Formation that contains primarily calcite with some aragonite and gypsum and a siliceous sinter from Octopus Spring that contains a variety of poorly crystalline to amorphous silicate minerals. Calcite was detected readily in the travertine rock using any one of the techniques studied. The small amount of gypsum was uniquely identified using XRD, VNIR, and mid-IR, while the aragonite was uniquely identified using XRD and Raman. The siliceous sinter sample was more difficult to characterize using each of these techniques and a combination of all techniques was more useful than any single technique. Although XRD is the historical standard for mineral identification, it presents some challenges for remote investigations. Thermal properties are most useful for minerals with discrete thermal transitions. Raman spectroscopy is most effective for detecting polarized species such as CO 3, OH, and CH, and exhibits sharp bands for most highly crystalline minerals when abundant. Mid-IR spectroscopy is most useful in characterizing Si-O (and metal-O) bonds and also has the advantage that remote information about sample texture (e.g., particle size) can be determined. Mid-IR spectroscopy is also sensitive to structural OH, CO 3, and SO 4 bonds when abundant. VNIR spectroscopy is best for characterizing metal excitational bands and water, and is also a good technique for identification of structural OH, CO 3, SO 4, or CH bonds. Combining multiple techniques provides the most comprehensive information about mineralogy because of the different selection rules and particle size sensitivities, in addition to maximum coverage of excitational and vibrational bands at all wavelengths. This study of hydrothermal rocks from Yellowstone provides insights on how to combine information from multiple instruments to identify mineralogy and hence evidence of water on Mars.

Bishop, Janice L.; Murad, Enver; Lane, Melissa D.; Mancinelli, Rocco L.

2004-06-01

386

Determination of total Pu content in a Spent Fuel Assembly by Measuring Passive Neutron Count rate and Multiplication with the Differential Die-Away Instrument  

SciTech Connect

A key objective of the Next Generation Safeguards Initiative (NGSI) is to evaluate and develop non-destructive assay (NDA) techniques to determine the elemental plutonium content in a commercial-grade nuclear spent fuel assembly (SFA) [1]. Within this framework, we investigate by simulation a novel analytical approach based on combined information from passive measurement of the total neutron count rate of a SFA and its multiplication determined by the active interrogation using an instrument based on a Differential Die-Away technique (DDA). We use detailed MCNPX simulations across an extensive set of SFA characteristics to establish the approach and demonstrate its robustness. It is predicted that Pu content can be determined by the proposed method to a few %.

Henzl, Vladimir [Los Alamos National Laboratory; Croft, Stephen [Los Alamos National Laboratory; Swinhoe, Martyn T. [Los Alamos National Laboratory; Tobin, Stephen J. [Los Alamos National Laboratory

2012-07-18

387

Trypanosoma cruzi: Synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts  

PubMed Central

The parasite Trypanasoma cruzi is responsible for Chagas disease and its triatomine vector, Rhodnius prolixus, has a symbiotic relationship with the soil bacterium, Rhodococcus rhodnii. R. rhodnii that was previously genetically engineered to produce the anti-microbial peptide, cecropin A was co-infected with T. cruzi into R. prolixus resulting in clearance of the infectious T. cruzi in 65% of the vectors. Similar anti-microbial peptides have been isolated elsewhere and were studied for differential toxicity against T. cruzi and R. rhodnii. Of the six anti-microbial peptides tested, apidaecin, magainin II, melittin, and cecropin A were deemed potential candidates for the Chagas paratransgenic system as they were capable of killing T. cruzi at concentrations that exhibit little or no toxic effects on R. rhodnii. Subsequent treatments of T. cruzi with these peptides in pair-wise combinations resulted in synergistic killing, indicating that improvement of the 65% parasite clearance seen in previous experiments may be possible utilizing combinations of different anti-microbial peptides. PMID:20206169

Fieck, Annabeth; Hurwitz, Ivy; S.Kang, Angray; Durvasula, Ravi

2010-01-01

388

Trypanosoma cruzi: synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts.  

PubMed

The parasite Trypanasoma cruzi is responsible for Chagas disease and its triatomine vector, Rhodnius prolixus, has a symbiotic relationship with the soil bacterium, Rhodococcus rhodnii. R. rhodnii that was previously genetically engineered to produce the anti-microbial peptide, cecropin A was co-infected with T. cruzi into R. prolixus resulting in clearance of the infectious T. cruzi in 65% of the vectors. Similar anti-microbial peptides have been isolated elsewhere and were studied for differential toxicity against T. cruzi and R. rhodnii. Of the six anti-microbial peptides tested, apidaecin, magainin II, melittin, and cecropin A were deemed potential candidates for the Chagas paratransgenic system as they were capable of killing T.cruzi at concentrations that exhibit little or no toxic effects on R. rhodnii. Subsequent treatments of T. cruzi with these peptides in pair-wise combinations resulted in synergistic killing, indicating that improvement of the 65% parasite clearance seen in previous experiments may be possible utilizing combinations of different anti-microbial peptides. PMID:20206169

Fieck, Annabeth; Hurwitz, Ivy; Kang, Angray S; Durvasula, Ravi

2010-08-01

389

Acquisition of multiple nuclei and the activity of DNA polymerase alpha and reinitiation of DNA replication in terminally differentiated adult cardiac muscle cells in culture  

SciTech Connect

Terminally differentiated ventricular cardiac muscle cells isolated from the adult rat and maintained in cell culture have been observed to acquire multiple nuclei. In one cultured myocyte as many as 10 nuclei have been counted. Apparently, these multiple nuclei are formed by DNA replication followed by karyokinesis; the cells must then fail to complete mitosis and divide. To investigate whether DNA synthesis was occurring, the cells were cultured in the presence of (3H)thymidine and then processed for autoradiography. Mononucleated, binucleated, and multinucleated cells incorporate (3H)thymidine into DNA as evidenced by the high concentration of silver grains over their nuclei. Peak periods of incorporation were observed to occur at 10- to 12-day intervals; at 11, 23, and 33 days after initially placing the cells in culture. When the cells were maintained in the presence of (3H)thymidine continuously from Day 7 to Day 17 of culture, 23% of the cells became labeled. If the cells were cultured continuously for 30 days in the presence of (3H)thymidine, from Day 10 to Day 40, 56% of the cells were labeled. Isopycnic gradient analysis indicates that this thymidine incorporation was into DNA that was being replicated semiconservatively; these experiments did not eliminate the possibility, however, that this incorporation was due to amplification of specific genes, such as those coding for the contractile proteins. The activity of DNA polymerase alpha also returns to these cells. These studies demonstrate that the terminally differentiated mammalian ventricular cardiac muscle cell, previously thought to have permanently lost the capacity to replicate DNA during early development, is able to reinitiate semiconservative DNA replication when grown in culture.

Claycomb, W.C.; Bradshaw, H.D. Jr.

1983-10-01

390

Rapid differentiation of bacterial species with multiple probes of different lengths in a single slot blot hybridization.  

PubMed Central

We describe a highly efficient method for dot and slot blot hybridizations with multiple oligonucleotide probes for high throughput identification of organisms and studies of microbial community structures. Several probes with distinct specificities were designed to have the same melting temperature but unique lengths by adding different numbers of nonspecific nucleotides to one end. All of the probes were mixed, labelled with 32P, and hybridized to one piece of membrane on which genes coding for 16S rRNAs from different bacterial species had been immobilized. After hybridization, the bound probes were eluted and resolved on a denaturing polyacrylamide gel and the identities of the genes coding for 16S rRNAs were read from an autoradiograph of the gel. The results from the application of this technique to pure actinomycete cultures are reported here. PMID:8534094

Wang, G C; Wang, Y

1995-01-01

391

Antiseizure Drugs Differentially Modulate Theta-Burst Induced Long-Term Potentiation in C57BL/6 Mice  

PubMed Central

Summary Objective Cognitive comorbidities are increasingly recognized as an equal (or even more disabling) aspect of epilepsy. Additionally, the actions of some antiseizure drugs (ASDs) can impact learning and memory. Accordingly, the NINDS epilepsy research benchmarks call for the implementation of standardized protocols for screening ASDs for their amelioration or exacerbation of cognitive comorbidities. Long-term potentiation (LTP) is a widely used model for investigating synaptic plasticity and its relationship to learning and memory. While the effects of some ASDs on LTP have been examined, none of these studies employed physiologically relevant induction stimuli such as theta-burst stimulation (TBS). To systematically evaluate the effects of multiple ASDs in the same preparation using physiologically relevant stimulation protocols, we examined the effects of a broad panel of existing ASDs on TBS-induced LTP in area CA1 of in-vitro brain slices, prepared in either normal or sucrose-based ACSF, from C57BL/6 mice. Methods Coronal brain slices containing the dorsal hippocampus were made using either standard or sucrose-based ACSF. Recordings were obtained from four slices at a time using the Scientifica Slicemaster high throughput recording system. Slices exposed to ASDs were paired with slices from the opposite hemisphere that served as controls. Field excitatory post-synaptic potentials (fEPSPs) were recorded, and all ASDs were applied to slices by bath perfusion for 20 minutes prior to the induction stimulus. LTP was induced by TBS or by high-frequency stimulation (HFS). The following ASDs were examined: 100 µM phenobarbital (PB), 80 µM phenytoin (PHT), 50 µM carbamazepine (CBZ), 600 µM valproate (VPA), 60 µM topiramate (TPM), 60 µM lamotrigine (LTG), 100 µM levetiracetam (LEV), 10 µM ezogabine (EZG), and 30 µM tiagabine (TGB). Results Among voltage-gated sodium channel inhibitors, CBZ significantly attenuated TBS-induced LTP, PHT attenuated both TBS-induced LTP and post-tetanic potentiation (PTP), and LTG failed to affect LTP but did attenuate PTP. ASDs that modulate GABAergic synaptic transmission, such as PB and TGB, significantly attenuated LTP in brain slices prepared in sucrose-based ACSF but not standard ACSF. Third generation ASDs, such as LEV and TPM, did not affect LTP in ACSF- or sucrose-prepared brain slices. While EZG failed to affect LTP, it did significantly attenuate PTP under both slicing conditions. VPA failed to affect LTP in area CA1, both in C57BL/6 mice and Sprague Dawley rats, using TBS or HFS. However, VPA did attenuate TBS-induced LTP in the dentate gyrus (DG). PMID:24447124

West, Peter J.; Saunders, Gerald W.; Remigio, Gregory J.; Wilcox, Karen S.; White, H. Steve

2014-01-01

392

Seed dimorphism, nutrients and salinity differentially affect seed traits of the desert halophyte Suaeda aralocaspica via multiple maternal effects  

PubMed Central

Background Maternal effects may influence a range of seed traits simultaneously and are likely to be context-dependent. Disentangling the interactions of plant phenotype and growth environment on various seed traits is important for understanding regeneration and establishment of species in natural environments. Here, we used the seed-dimorphic plant Suaeda aralocaspica to test the hypothesis that seed traits are regulated by multiple maternal effects. Results Plants grown from brown seeds had a higher brown:black seed ratio than plants from black seeds, and germination percentage of brown seeds was higher than that of black seeds under all conditions tested. However, the coefficient of variation (CV) for size of black seeds was higher than that of brown seeds. Seeds had the smallest CV at low nutrient and high salinity for plants from brown seeds and at low nutrient and low salinity for plants from black seeds. Low levels of nutrients increased size and germinability of black seeds but did not change the seed morph ratio or size and germinability of brown seeds. High levels of salinity decreased seed size but did not change the seed morph ratio. Seeds from high-salinity maternal plants had a higher germination percentage regardless of level of germination salinity. Conclusions Our study supports the multiple maternal effects hypothesis. Seed dimorphism, nutrient and salinity interacted in determining a range of seed traits of S. aralocaspica via bet-hedging and anticipatory maternal effects. This study highlights the importance of examining different maternal factors and various offspring traits in studies that estimate maternal effects on regeneration. PMID:23006315

2012-01-01

393

Mimicking the Neurotrophic Factor Profile of Embryonic Spinal Cord Controls the Differentiation Potential of Spinal Progenitors into Neuronal Cells  

PubMed Central

Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT)-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively. PMID:21698095

Nakamura, Masaya; Tsuji, Osahiko; Bregman, Barbara S.; Toyama, Yoshiaki; Okano, Hideyuki

2011-01-01

394

The Potential of Gait Analysis to Contribute to Differential Diagnosis of Early Stage Dementia: Current Research and Future Directions  

ERIC Educational Resources Information Center

Early differential diagnosis of dementia is becoming increasingly important as new pharmacologic therapies are developed, as these treatments are not equally effective for all types of dementia. Early detection and differential diagnosis also facilitates informed family decision making and timely access to appropriate services. Information about…