Sample records for multiple differentiation potential

  1. Isolation and Multiple Differentiation Potential Assessment of Human Gingival Mesenchymal Stem Cells

    PubMed Central

    Gao, Yuan; Zhao, Guizhi; Li, Dongxia; Chen, Xin; Pang, Jianliang; Ke, Jie

    2014-01-01

    The aim of this study was to isolate human mesenchymal stem cells (MSCs) from the gingiva (GMSCs) and confirm their multiple differentiation potentials, including the odontogenic lineage. GMSCs, periodontal ligament stem cells (PDLSCs) and dermal stem cells (DSCs) cultures were analyzed for cell shape, cell cycle, colony-forming unit-fibroblast (CFU-F) and stem cell markers. Cells were then induced for osteogenic and adipogenic differentiation and analyzed for differentiation markers (alkaline phosphatase (ALP) activity, mineralization nodule formation and Runx2, ALP, osteocalcin (OCN) and collagen I expressions for the osteogenic differentiation, and lipid vacuole formation and PPAR?-2 expression for the adipogenic differentiation). Besides, the odontogenic differentiation potential of GMSCs induced with embryonic tooth germ cell-conditioned medium (ETGC-CM) was observed. GMSCs, PDLSCs and DSCs were all stromal origin. PDLSCs showed much higher osteogenic differentiation ability but lower adipogenic differentiation potential than DSCs. GMSCs showed the medial osteogenic and adipogenic differentiation potentials between those of PDLSCs and DSCs. GMSCs were capable of expressing the odontogenic genes after ETGC-CM induction. This study provides evidence that GMSCs can be used in tissue engineering/regeneration protocols as an approachable stem cell source. PMID:25405732

  2. Multiple symbol differential detection

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (inventor); Simon, Marvin K. (inventor)

    1991-01-01

    A differential detection technique for multiple phase shift keying (MPSK) signals is provided which uses a multiple symbol observation interval on the basis of which a joint decision is made regarding the phase of the received symbols. In accordance with the invention, a first difference phase is created between first and second received symbols. Next, the first difference phase is correlated with the possible values thereof to provide a first plurality of intermediate output signals. A second difference phase is next created between second and third received symbols. The second difference phase is correlated with plural possible values thereof to provide a second plurality of intermediate output signals. Next, a third difference phase is created between the first and third symbols. The third difference phase is correlated with plural possible values thereof to provide a third plurality of intermediate output signals. Each of the first plurality of intermediate outputs are combined with each of the second plurality of intermediate outputs and each of the third plurality of intermediate outputs to provide a plurality of possible output values. Finally, a joint decision is made by choosing from the plurality of possible output values the value which represents the best combined correlation of the first, second and third difference values with the possible values thereof.

  3. Comparative Study on the Therapeutic Potential of Neurally Differentiated Stem Cells in a Mouse Model of Multiple Sclerosis

    Microsoft Academic Search

    Natalie L. Payne; Guizhi Sun; Daniella Herszfeld; Pollyanna A. Tat-Goh; Paul J. Verma; Helena C. Parkington; Harold A. Coleman; Mary A. Tonta; Christopher Siatskas; Claude C. A. Bernard

    2012-01-01

    BackgroundTransplantation of neural stem cells (NSCs) is a promising novel approach to the treatment of neuroinflammatory diseases such as multiple sclerosis (MS). NSCs can be derived from primary central nervous system (CNS) tissue or obtained by neural differentiation of embryonic stem (ES) cells, the latter having the advantage of readily providing an unlimited number of cells for therapeutic purposes. Using

  4. Multiple bit differential detection of offset QPSK

    NASA Technical Reports Server (NTRS)

    Simon, M.

    2003-01-01

    Analogous to multiple symbol differential detection of quadrature phase-shift-keying, 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.

  5. Multiple-Bit Differential Detection of OQPSK

    NASA Technical Reports Server (NTRS)

    Simon, Marvin

    2005-01-01

    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).

  6. Evoked potentials for evaluation of multiple sclerosis.

    PubMed

    Fuhr, P; Kappos, L

    2001-12-01

    The role of evoked potentials (EP) in the assessment of multiple sclerosis (MS) has changed over the last decade. This is largely due to progress in imaging techniques. But while MRI has a greater diagnostic sensitivity, EP remain a useful diagnostic tool in many clinical situations. Moreover, recent studies demonstrate the utility of EP for monitoring and predicting the course of the disease in patient groups, although not yet in individuals. For these purposes, EP show better results than conventional MRI. In the near future, new developments in electrophysiology, immunology and imaging may allow to differentiate between different subtypes of MS early in the course, and consequently to tailor therapeutic measures more precisely to the individual patients. PMID:11738188

  7. NaCl Potentiates Human Fibrocyte Differentiation

    PubMed Central

    Cox, Nehemiah; Pilling, Darrell; Gomer, Richard H.

    2012-01-01

    Excessive NaCl intake is associated with a variety of fibrosing diseases such as renal and cardiac fibrosis. This association has been attributed to increased blood pressure as the result of high NaCl intake. However, studies in patients with high NaCl intake and fibrosis reveal a connection between NaCl intake and fibrosis that is independent of blood pressure. We find that increasing the extracellular concentration of NaCl to levels that may occur in human blood after high-salt intake can potentiate, in serum-free culture conditions, the differentiation of freshly-isolated human monocytes into fibroblast-like cells called fibrocytes. NaCl affects the monocytes directly during their adhesion. Potassium chloride and sodium nitrate also potentiate fibrocyte differentiation. The plasma protein Serum Amyloid P (SAP) inhibits fibrocyte differentiation. High levels of extracellular NaCl change the SAP Hill coefficient from 1.7 to 0.8, and cause a four-fold increase in the concentration of SAP needed to inhibit fibrocyte differentiation by 95%. Together, our data suggest that NaCl potentiates fibrocyte differentiation. NaCl-increased fibrocyte differentiation may thus contribute to NaCl-increased renal and cardiac fibrosis. PMID:23029177

  8. A Clinical Approach to the Differential Diagnosis of Multiple Sclerosis.

    PubMed

    Toledano, Michel; Weinshenker, Brian G; Solomon, Andrew J

    2015-08-01

    The diagnostic criteria for multiple sclerosis (MS) rely on clinical, paraclinical, and radiographic findings of limited specificity. Many disorders mimic MS, and the decision of when to investigate an alternative diagnosis can be challenging. Reliance on extensive ancillary testing to exclude potential mimics, however, is unnecessary in most cases. Rather, recognition and rigorous interpretation of "classic" clinical and radiographic features of MS are often sufficient to establish the diagnosis. Misinterpretation of the clinical and radiographic diagnostic criteria for MS in the setting of more common diseases and syndromes and a lack of vigilance for "red flags" are important contributors to misdiagnosis. A clinical framework for the differential diagnosis of MS that emphasizes phenotypes atypical for MS and suggests diseases or syndromes in which they more commonly occur may be an important diagnostic guide for clinicians in contemporary practice. PMID:26112766

  9. Multiple model simulation: modelling cell division and differentiation in the

    E-print Network

    Stepney, Susan

    behaviours are simulated in the modified-prostate simulation; (c) to experiment with the vari- ous formsMultiple model simulation: modelling cell division and differentiation in the prostate Alastair this approach to building a model of prostate cell division and differentiation, with each model layer

  10. Differentiating multiple-system atrophy from Parkinson's disease.

    PubMed

    Ramli, N; Nair, S R; Ramli, N M; Lim, S Y

    2015-05-01

    The purpose of this review is to illustrate the differentiating features of multiple-system atrophy from Parkinson's disease at MRI. The various MRI sequences helpful in the differentiation will be discussed, including newer methods, such as diffusion tensor imaging, MR spectroscopy, and nuclear imaging. PMID:25752581

  11. Effect of Multiple Testing Adjustment in Differential Item Functioning Detection

    ERIC Educational Resources Information Center

    Kim, Jihye; Oshima, T. C.

    2013-01-01

    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…

  12. PPAR-?: Therapeutic Potential for Multiple Sclerosis

    PubMed Central

    Drew, Paul D.; Xu, Jihong; Racke, Michael K.

    2008-01-01

    The role of peroxisome proliferator-activated receptors (PPARs) in altering lipid and glucose metabolism is well established. More recent studies indicate that PPARs also play critical roles in controlling immune responses. We and others have previously demonstrated that PPAR-? agonists modulate the development of experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). This review will discuss the cellular and molecular mechanisms by which these agonists are believed to modulate disease. The therapeutic potential of PPAR-? agonists in the treatment of multiple sclerosis will also be considered. PMID:18604287

  13. Multiple symbol differential detection of uncoded and trellis coded MPSK

    NASA Technical Reports Server (NTRS)

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

    1989-01-01

    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.

  14. Differential Multiple-Valued Logic Using Resonant Tunneling Diodes

    Microsoft Academic Search

    Lutz J. Micheel; Michael J. Paulus

    1990-01-01

    Differential multiple-valued logic (MVL) based on resonant tunneling diodes (RTDs) and heterojunction bipolar transistors is described. The novel gates are of the emitter-coupled current-switch type and can implement a wide range of MVL functions, including sums of products and multiple-threshold elements. One of the gates consists of diodes performing the input-thresholding functions and current switches generating the summation currents; the

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

    ERIC Educational Resources Information Center

    Shih, Ching-Lin; Wang, Wen-Chung

    2009-01-01

    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,…

  16. Differential Birkhoff decomposition and the renormalization of multiple zeta values

    Microsoft Academic Search

    Li Guo; Bin Zhang

    2007-01-01

    In the Hopf algebra approach of Connes and Kreimer on renormalization of quantum field theory, the renormalization process is views as a special case of the Algebraic Birkhoff Decomposition. We give a differential algebra variation of this decomposition and apply this to the study of multiple zeta values.

  17. Detection of Differential Item Functioning in Multiple Groups.

    ERIC Educational Resources Information Center

    Kim, Seock-Ho; And Others

    Detection of differential item functioning (DIF) is most often done between two groups of examinees under item response theory. It is sometimes important, however, to determine whether DIF is present in more than two groups. A method is presented for the detection of DIF in multiple groups. The method, the Q(sub j) statistic, is closely related to…

  18. Differentiation of Self and Child Abuse Potential in Young Adulthood

    ERIC Educational Resources Information Center

    Skowron, Elizabeth A.; Platt, Lisa F.

    2005-01-01

    The authors examine the role of Bowen family systems theory in predicting physical child abuse potential. Relations between differentiation of self, perceptions of personal problem-solving skills, and child abuse potential were tested in a sample of 210 single young adults who were not yet parents. Greater differentiation of self that is, lower…

  19. [Differential diagnosis of dissociative identity disorder (multiple personality disorder)].

    PubMed

    Stübner, S; Völkl, G; Soyka, M

    1998-05-01

    Recently the concept of dissociative identity disorder (formerly known as multiple personality disorder) has attracted increasing public and scientific interest. However, it is rarely diagnosed in the clinical setting. the reported case of a 47-year-old woman with a history of child abuse demonstrates the problems of differential diagnosis. A number of psychopathologic symptoms pointed to a multiple personality disorder, but in the follow-up psychotic symptoms such as delusions, possible hallucinations and bizarre behavior clearly emerged. The differential diagnosis of dissociative identity disorder includes paranoid schizophrenia, as in the case described, borderline personality disorder, hysteria, simulation and the false memory syndrome. Finally, social and cultural factors have to be considered. PMID:9629561

  20. Multiple-symbol differential detection of GMSK for mobile communications

    Microsoft Academic Search

    Andrea Abrardo; Giuliano Benelli; Gianfranco R. Cau

    1995-01-01

    A new multiple differential detection (MDD) sequence estimator is described which uses a decision feedback for the demodulation of a GMSK signal. This technique is based upon a maximum-likelihood sequence estimation of the transmitted phases rather than on a symbol-by-symbol detection. An upper and a lower bound on the bit error probability of the described detector in the case of

  1. Differential Shunting of EPSPs by Action Potentials

    Microsoft Academic Search

    Michael Häusser; Guy Major; Greg J. Stuart

    2001-01-01

    Neurons encode information and communicate via action potentials, which are generated following the summation of synaptic events. It is commonly assumed that action potentials reset the membrane potential completely, allowing another round of synaptic integration to begin. We show here that the conductances underlying the action potential act instead as a variable reset of synaptic integration. The strength of this

  2. Differential shunting of EPSPs by action potentials.

    PubMed

    Häusser, M; Major, G; Stuart, G J

    2001-01-01

    Neurons encode information and communicate via action potentials, which are generated following the summation of synaptic events. It is commonly assumed that action potentials reset the membrane potential completely, allowing another round of synaptic integration to begin. We show here that the conductances underlying the action potential act instead as a variable reset of synaptic integration. The strength of this reset is cell type-specific and depends on the kinetics, location, and timing of the synaptic input. As a consequence, distal synapses, as well as inputs mediated by N-methyl-d-aspartate receptor activation, can contribute disproportionately to synaptic integration during action potential firing. PMID:11141567

  3. [Multiple sclerosis: diagnosis, clinical course and differential diagnosis].

    PubMed

    Tomioka, Ryo; Matsui, Makoto

    2014-11-01

    Disease modifying treatment for multiple sclerosis has improved both relapse rate and prognosis. The diagnostic criteria of McDonald were designed for early diagnosis, with a crucial role for magnetic resonance imaging in the 2010 revision, as dissemination in space and time can be established by a single scan. These criteria are likely applicable in pediatric, Asian, and Latin America populations, and include neuromyelitis optica as a differential diagnosis. With recent modifications for widespread use, diagnostic sensitivity and specificity have been improved. Nevertheless, clinical and imaging red flags for atypical manifestations are needed for exclusion of alternative diagnosis. PMID:25518377

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

    E-print Network

    Powers, Robert

    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

  5. Multiple Signals Converge on a Differentiation MAPK Pathway

    PubMed Central

    Chavel, Colin A.; Dionne, Heather M.; Birkaya, Barbara; Joshi, Jyoti; Cullen, Paul J.

    2010-01-01

    An important emerging question in the area of signal transduction is how information from different pathways becomes integrated into a highly coordinated response. In budding yeast, multiple pathways regulate filamentous growth, a complex differentiation response that occurs under specific environmental conditions. To identify new aspects of filamentous growth regulation, we used a novel screening approach (called secretion profiling) that measures release of the extracellular domain of Msb2p, the signaling mucin which functions at the head of the filamentous growth (FG) MAPK pathway. Secretion profiling of complementary genomic collections showed that many of the pathways that regulate filamentous growth (RAS, RIM101, OPI1, and RTG) were also required for FG pathway activation. This regulation sensitized the FG pathway to multiple stimuli and synchronized it to the global signaling network. Several of the regulators were required for MSB2 expression, which identifies the MSB2 promoter as a target “hub” where multiple signals converge. Accessibility to the MSB2 promoter was further regulated by the histone deacetylase (HDAC) Rpd3p(L), which positively regulated FG pathway activity and filamentous growth. Our findings provide the first glimpse of a global regulatory hierarchy among the pathways that control filamentous growth. Systems-level integration of signaling circuitry is likely to coordinate other regulatory networks that control complex behaviors. PMID:20333241

  6. Analysis of direct current potential field around multiple random cracks

    Microsoft Academic Search

    N. Tada; Y. Hayashi; T. Kitamura; R. Ohtani

    1996-01-01

    A method for evaluating the distribution of electrical potential around multiple through cracks is proposed. The method gives accurate potential values for cracks with different lengths at random positions by combining theoretical potential functions for a single crack in an infinite plate. The validity of the method is numerically confirmed with respect to problems of a single and three cracks

  7. [Differential diagnosis of multiple sclerosis and autoimmune rheumatic diseases].

    PubMed

    Brola, Waldemar; Fudala, Ma?gorzata; Kasprzyk, Marta; Opara, Józef

    2013-01-01

    Multiple sclerosis (MS) is a progressive demyelinating-inflammatory disease of the central nervous system, probably of autoimmune etiology. Characteristic qualities include multifocal demyelination, which result in varied clinical pictures of the disease. MS must be differentiated from chronic or recurring diseases, as well as from those with multifocal neurological manifestations and multifocal lesions revealed in a MR scan. Particular signs may precede the development of the full-blown MS, but they may be initial manifestations of autoimmune disease such as systemic lupus, antiphospholipid syndrome, Behçet's disease or Sjögren's syndrome as well. Diagnosis is easier in the later stages due to appearance of characteristic manifestations, absent in the course of MS. Nevertheless, the mildly symptomatic nature of those diseases may lead to misdiagnosis, putting the patient at risk of an expensive and inefficient treatment, which may only exacerbate the symptoms. In many cases a long-term follow-up is necessary to confirm the diagnosis. PMID:25775811

  8. Differential Fault Analysis of AES using a Single Multiple-Byte Fault

    E-print Network

    Differential Fault Analysis of AES using a Single Multiple-Byte Fault Subidh Ali1 , Debdeep presents an improvement on a recently pub- lished differential fault analysis of AES that requires one] proposed the idea of Differential Fault Analysis (DFA), based on differential cryptanalysis, to attack DES

  9. Local random potentials of high differentiability to model the Landscape

    E-print Network

    Thorsten Battefeld; Chirag Modi

    2015-03-10

    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.

  10. Local random potentials of high differentiability to model the Landscape

    NASA Astrophysics Data System (ADS)

    Battefeld, T.; Modi, C.

    2015-03-01

    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.

  11. LeafWaterPotential ofDifferentially Salinized Plants

    Microsoft Academic Search

    W. R. Gardner; C. Gerloff

    1969-01-01

    Waterandosmotic potential energies were measuredwiththermocouple psv- chrometers, atintervals during a 4-week period, ingrowing leaves ofbean(Phaseolus vulgaris, var.BlueLake) andbarley (Hordeum vulgare, var.Liberty) plants having rootsequally split between 2 differentially salinized nutrient solutions. Theosmoticpotentials ofplants with halftheir rootsinsaline solutions wereabouthalfway between theosmoticpotentials ofplants growninnonsaline solutions andthose growninsaline solutions. By theendofthe4-week measurementperiod, thebeansandbarley werealmostmature.The finaldryweights of shoots ofplants withhalftheir rootsinsaline solutions were abouthalfway

  12. Biophysical Characteristics Reveal Neural Stem Cell Differentiation Potential

    PubMed Central

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

    2011-01-01

    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

  13. Composition-Diamond lemma for $\\lambda$-differential associative algebras with multiple operators

    E-print Network

    Qiu, Jianjun

    2009-01-01

    In this paper, we establish the Composition-Diamond lemma for $\\lambda$-differential associative algebras over a field $K $ with multiple operators. As applications, we obtain Gr\\"{o}bner-Shirshov bases of free $\\lambda$-differential Rota-Baxter algebras. In particular, linear bases of free $\\lambda$-differential Rota-Baxter algebras are obtained and consequently, the free $\\lambda$-differential Rota-Baxter algebras are constructed by words.

  14. The neuroprotective potential of flavonoids: a multiplicity of effects

    Microsoft Academic Search

    David Vauzour; Katerina Vafeiadou; Ana Rodriguez-Mateos; Catarina Rendeiro; Jeremy P. E. Spencer

    2008-01-01

    Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against\\u000a injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and\\u000a cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein\\u000a and lipid kinase signalling cascades in the brain

  15. Differentiation and quantification of inflammation, demyelination and axon injury or loss in multiple sclerosis.

    PubMed

    Wang, Yong; Sun, Peng; Wang, Qing; Trinkaus, Kathryn; Schmidt, Robert E; Naismith, Robert T; Cross, Anne H; Song, Sheng-Kwei

    2015-05-01

    Axon injury/loss, demyelination and inflammation are the primary pathologies in multiple sclerosis lesions. Despite the prevailing notion that axon/neuron loss is the substrate of clinical progression of multiple sclerosis, the roles that these individual pathological processes play in multiple sclerosis progression remain to be defined. An imaging modality capable to effectively detect, differentiate and individually quantify axon injury/loss, demyelination and inflammation, would not only facilitate the understanding of the pathophysiology underlying multiple sclerosis progression, but also the assessment of treatments at the clinical trial and individual patient levels. In this report, the newly developed diffusion basis spectrum imaging was used to discriminate and quantify the underlying pathological components in multiple sclerosis white matter. Through the multiple-tensor modelling of diffusion weighted magnetic resonance imaging signals, diffusion basis spectrum imaging resolves inflammation-associated cellularity and vasogenic oedema in addition to accounting for partial volume effects resulting from cerebrospinal fluid contamination, and crossing fibres. Quantitative histological analysis of autopsied multiple sclerosis spinal cord specimens supported that diffusion basis spectrum imaging-determined cellularity, axon and myelin injury metrics closely correlated with those pathologies identified and quantified by conventional histological staining. We demonstrated in healthy control subjects that diffusion basis spectrum imaging rectified inaccurate assessments of diffusion properties of white matter tracts by diffusion tensor imaging in the presence of cerebrospinal fluid contamination and/or crossing fibres. In multiple sclerosis patients, we report that diffusion basis spectrum imaging quantitatively characterized the distinct pathologies underlying gadolinium-enhanced lesions, persistent black holes, non-enhanced lesions and non-black hole lesions, a task yet to be demonstrated by other neuroimaging approaches. Diffusion basis spectrum imaging-derived radial diffusivity (myelin integrity marker) and non-restricted isotropic diffusion fraction (oedema marker) correlated with magnetization transfer ratio, supporting previous reports that magnetization transfer ratio is sensitive not only to myelin integrity, but also to inflammation-associated oedema. Our results suggested that diffusion basis spectrum imaging-derived quantitative biomarkers are highly consistent with histology findings and hold promise to accurately characterize the heterogeneous white matter pathology in multiple sclerosis patients. Thus, diffusion basis spectrum imaging can potentially serve as a non-invasive outcome measure to assess treatment effects on the specific components of underlying pathology targeted by new multiple sclerosis therapies. PMID:25724201

  16. Application of Differential Evolution Algorithm on Self-Potential Data

    PubMed Central

    Li, Xiangtao; Yin, Minghao

    2012-01-01

    Differential evolution (DE) is a population based evolutionary algorithm widely used for solving multidimensional global optimization problems over continuous spaces, and has been successfully used to solve several kinds of problems. In this paper, differential evolution is used for quantitative interpretation of self-potential data in geophysics. Six parameters are estimated including the electrical dipole moment, the depth of the source, the distance from the origin, the polarization angle and the regional coefficients. This study considers three kinds of data from Turkey: noise-free data, contaminated synthetic data, and Field example. The differential evolution and the corresponding model parameters are constructed as regards the number of the generations. Then, we show the vibration of the parameters at the vicinity of the low misfit area. Moreover, we show how the frequency distribution of each parameter is related to the number of the DE iteration. Experimental results show the DE can be used for solving the quantitative interpretation of self-potential data efficiently compared with previous methods. PMID:23240004

  17. Cardiac side population cells exhibit endothelial differentiation potential.

    PubMed

    Yoon, Jihyun; Choi, Seung Cheol; Park, Chi Yeon; Shim, Wan Joo; Lim, Do-Sun

    2007-10-31

    Recent studies have shown that side population (SP) cells, isolated from adult myocardium, represent a distinct cardiac progenitor cell population that exhibits functional cardiomyogenic differentiation. However, information on the intrinsic characteristics and endothelial potential, of cardiac SP cells, is limited. The present study was designed to investigate whether cardiac SP cells exhibit endothelial differentiation potential. The cardiac SP cells more highly expressed the early cardiac transcription factors as well as endothelial cell markers compared to the bone marrow-SP cells. After treatment with VEGF, for 28 days, cardiac SP cells were able to differentiate into endothelial cells expressing von Willebrand factor as determined by immunocytochemistry. Furthermore, expression of endothelial cell markers increased several-fold in VEGF-treated cardiac SP cells compared to the control group when assessed by real-time PCR. We also confirmed that cardiac SP cells provided a significantly augmented ratio of ischemic/normal blood flow, in the cardiac SP cell-transplanted group compared with saline-treated controls on postoperative days 7, 14, 21 and 28, in a murine model. These results show that cardiac SP cells may contribute to regeneration of injured heart tissues partly by transdifferentiation into angiogenic lineages. PMID:18059141

  18. Communication: Separable potential energy surfaces from multiplicative artificial neural networks

    NASA Astrophysics Data System (ADS)

    Koch, Werner; Zhang, Dong H.

    2014-07-01

    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.

  19. Communication: separable potential energy surfaces from multiplicative artificial neural networks.

    PubMed

    Koch, Werner; Zhang, Dong H

    2014-07-14

    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. PMID:25027992

  20. Communication: Separable potential energy surfaces from multiplicative artificial neural networks

    SciTech Connect

    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

    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.

  1. Differential biocide susceptibility of the multiple genotypes of Mycobacterium immunogenum.

    PubMed

    Selvaraju, Suresh B; Khan, Izhar U H; Yadav, Jagjit S

    2008-03-01

    The non-tuberculous mycobacterium Mycobacterium immunogenum colonizes industrial metalworking fluids (MWFs) presumably due to its relative resistance to the currently practiced biocides and has been implicated in occupational respiratory hazards, particularly hypersensitivity pneumonitis. With an aim to understand its inherent biocide susceptibility profile and survival potential in MWF, five different genotypes of this organism, including a reference genotype (700506) and four novel test genotypes (MJY-3, MJY-4, MJY-10 and MJY-12) isolated in our recent study from diverse MWF operations were evaluated. For this, two commercial biocide formulations, Grotan (Hexahydro-1,3,5-tris(2-hydroxyethyl)-s-triazine) and Kathon (5-chloro-2-methyl-4-isothiazolin-3-one) currently practiced for the control of microorganisms, including mycobacteria, in MWF operations were tested. Effect of the fluid matrix on the biocide susceptibility was investigated for the synthetic (S) and semi-synthetic (SS) MWF matrices. In general, the minimum inhibitory concentration values were higher for the HCHO-releasing biocide Grotan than the isothiazolone biocide Kathon. All genotypes (except the reference genotype) showed lower susceptibility in SS as compared to S fluid matrix for Grotan. However, in case of Kathon, a greater susceptibility was observed in SS fluid for majority of the test genotypes (MJY-3, 4 and 10). The test genotypes were more resistant than the reference genotype to either biocide in both fluid types. Furthermore, the individual genotypes showed differential biocidal susceptibility, with MJY-10 being the most resistant. These observations emphasize the importance of using the resistant genotypes of M. immunogenum as the test strains for formulation or development and evaluation of existing and novel biocides, for industrial applications. PMID:18196302

  2. Disulfiram Attenuates Osteoclast Differentiation In Vitro: A Potential Antiresorptive Agent

    PubMed Central

    Cheng, Tak S.; Pavlos, Nathan J.; Rea, Sarah; Dai, Kerong; Zheng, Ming H.

    2015-01-01

    Disulfiram (DSF), a cysteine modifying compound, has long been clinically employed for the treatment of alcohol addiction. Mechanistically, DSF acts as a modulator of MAPK and NF-?B pathways signaling pathways. While these pathways are crucial for osteoclast (OC) differentiation, the potential influence of DSF on OC formation and function has not been directly assessed. Here, we explore the pharmacological effects of DSF on OC differentiation, activity and the modulation of osteoclastogenic signaling cascades. We first analyzed cytotoxicity of DSF on bone marrow monocytes isolated from C57BL/6J mice. Upon the establishment of optimal dosage, we conducted osteoclastogenesis and bone resorption assays in the presence or absence of DSF treatment. Luciferase assays in RAW264.7 cells were used to examine the effects of DSF on major transcription factors activation. Western blot, reverse transcription polymerase chain reaction, intracellular acidification and proton influx assays were employed to further dissect the underlying mechanism. DSF treatment dose-dependently inhibited both mouse and human osteoclastogenesis, especially at early stages of differentiation. This inhibition correlated with a decrease in the expression of key osteoclastic marker genes including CtsK, TRAP, DC-STAMP and Atp6v0d2 as well as a reduction in bone resorption in vitro. Suppression of OC differentiation was found to be due, at least in part, to the blockade of several key receptor activators of nuclear factor kappa-B ligand (RANKL)-signaling pathways including ERK, NF-?B and NFATc1. On the other hand, DSF failed to suppress intracellular acidification and proton influx in mouse and human osteoclasts using acridine orange quenching and microsome-based proton transport assays. Our findings indicate that DSF attenuates OC differentiation via the collective suppression of several key RANKL-mediated signaling cascades, thus making it an attractive agent for the treatment of OC-mediated disorders. PMID:25928135

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

    NASA Technical Reports Server (NTRS)

    Simon, M.

    2003-01-01

    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.

  4. Differential Expression of Novel Potential Regulators in Hematopoietic Stem Cells

    PubMed Central

    2005-01-01

    The hematopoietic system is an invaluable model both for understanding basic developmental biology and for developing clinically relevant cell therapies. Using highly purified cells and rigorous microarray analysis we have compared the expression pattern of three of the most primitive hematopoietic subpopulations in adult mouse bone marrow: long-term hematopoietic stem cells (HSC), short-term HSC, and multipotent progenitors. All three populations are capable of differentiating into a spectrum of mature blood cells, but differ in their self-renewal and proliferative capacity. We identified numerous novel potential regulators of HSC self-renewal and proliferation that were differentially expressed between these closely related cell populations. Many of the differentially expressed transcripts fit into pathways and protein complexes not previously identified in HSC, providing evidence for new HSC regulatory units. Extending these observations to the protein level, we demonstrate expression of several of the corresponding proteins, which provide novel surface markers for HSC. We discuss the implications of our findings for HSC biology. In particular, our data suggest that cell–cell and cell–matrix interactions are major regulators of long-term HSC, and that HSC themselves play important roles in regulating their immediate microenvironment. PMID:16151515

  5. A blind analysis of a case of multiple personality using the semantic differential

    Microsoft Academic Search

    Charles E. Osgood; Zella Luria

    1954-01-01

    A case of multiple personality was analyzed by means of a new multidimensional scaling technique called the semantic differential. The results were compared with the findings of clinical observation. The three personalities and their changes through time were presented by means of the semantic differential to indicate the effectiveness of this technique as a clinical tool.

  6. A New Differential Modulation for Coded OFDM with Multiple Transmit Antennas

    Microsoft Academic Search

    Hongbin Li

    2005-01-01

    A new differential modulation scheme is presented for coded orthogonal frequency-division multiplexing (OFDM) systems with multiple transmit antennas in frequency- and time- selective channels. In contrast to an earlier scheme that involves differential modulation in space and time (ST) across two code matrices, the new scheme performs it in space and frequency (SF) within only one code matrix. As such,

  7. A new differential modulation for coded OFDM with multiple transmit antennas

    Microsoft Academic Search

    Hongbin Li; Tao Li

    2006-01-01

    A new differential modulation scheme is presented for coded orthogonal frequency-division multiplexing (OFDM) systems with multiple transmit antennas in frequency- and time-selective channels. In contrast to an earlier scheme that involves differential modulation in space and time (ST) across two code matrices, the new scheme performs it in space and frequency (SF) within only one code matrix. As such, the

  8. Vestibular evoked myogenic potentials in multiple sclerosis patients

    Microsoft Academic Search

    Maurizio Versino; Silvia Colnaghi; Roberto Callieco; Roberto Bergamaschi; Alfredo Romani; Vittorio Cosi

    2002-01-01

    Objectives: Vestibular evoked myogenic potentials (VEMPs) are saccular responses to loud acoustic stimuli and are recordable from the sterno-cleido-mastoid muscle ipsilaterally to the stimulated ear. This study aimed to investigate VEMPs in patients suffering from multiple sclerosis (MS), and to compare these findings with both clinical and instrumental data.Methods: We recorded VEMPs from 70 MS patients, whose clinical data were

  9. A Study of Impulsive Multiterm Fractional Differential Equations with Single and Multiple Base Points and Applications

    PubMed Central

    Liu, Yuji; Ahmad, Bashir

    2014-01-01

    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

  10. Multiple-Resource Request Scheduling for Differentiated QoS at Website Gateway

    Microsoft Academic Search

    Ying-dar Lin; Ching-ming Tien; Shih-chiang Tsao; Ruo-hua Feng; Yuan-cheng Lai

    2008-01-01

    Differentiated quality of service is a way for a website operator to provide different service levels to its clients. Traditional HTTP request scheduling schemes can achieve this, but they schedule requests to manage only one server resource, such as CPU or disk I\\/ O. Actually, processing a request on the server will consume multiple resources. This paper presents a multiple-resource

  11. Multiple-resource request scheduling for differentiated QoS at website gateway

    Microsoft Academic Search

    Ying-Dar Lin; Ching-Ming Tien; Shih-Chiang Tsao; Ruo-Hua Feng; Yuan-Cheng Lai

    2008-01-01

    Differentiated quality of service is a way for a website operator to provide different service levels to its clients. Traditional HTTP request scheduling schemes can achieve this, but they schedule requests to manage only one server resource, such as CPU or disk I\\/O. Actually, processing a request on the server will consume multiple resources. This paper presents a multiple-resource request

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

    E-print Network

    Dunn, Casey

    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

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

    PubMed Central

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

    2014-01-01

    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

  14. Developing Teacher Leadership in Singapore: Multiple Pathways for Differentiated Journeys

    ERIC Educational Resources Information Center

    Goodwin, A. Lin; Low, Ee Ling; Ng, Pak Tee

    2015-01-01

    In this article, we examine quality teachers through teacher leadership development. Using Singapore as an illustrative case, we describe the redefinition of the teaching profession to include deliberate structures and multiple pathways designed to nurture teacher leaders, and the role of teacher leaders in supporting education reform. We go on to…

  15. Differential diagnosis of posterior fossa multiple sclerosis lesions - neuroradiological aspects

    Microsoft Academic Search

    A. Falini; C. Kesavadas; S. Pontesilli; M. Rovaris; G. Scotti

    2001-01-01

    . Various infratentorial pathological conditions can mimic multiple sclerosis (MS) both clinically and radiologically. We review the inflammatory, vascular, neoplastic and metabolic conditions which show features similar to those of MS on magnetic resonance imaging (MRI). Beçet's disease, Lyme disease, progressive multifocal leukoencephalopathy, neurosarcoidosis, Whipple's disease, listeria rhombencephalitis, Bickerstaff's brainstem encephalitis, vascultis due to systemic lupus erythematosus, and acute disseminated

  16. Differential Detection of Tumor Cells Using a Combination of Cell Rolling, Multivalent Binding, and Multiple Antibodies

    PubMed Central

    2015-01-01

    Effective quantification and in situ identification of circulating tumor cells (CTCs) in blood are still elusive because of the extreme rarity and heterogeneity of the cells. In our previous studies, we developed a novel platform that captures tumor cells at significantly improved efficiency in vitro using a unique biomimetic combination of two physiological processes: E-selectin-induced cell rolling and poly(amidoamine) (PAMAM) dendrimer-mediated strong multivalent binding. Herein, we have engineered a novel multifunctional surface, on the basis of the biomimetic cell capture, through optimized incorporation of multiple antibodies directed to cancer cell-specific surface markers, such as epithelial cell adhesion molecule (EpCAM), human epidermal growth factor receptor-2 (HER-2), and prostate specific antigen (PSA). The surfaces were tested using a series of tumor cells, MDA-PCa-2b, MCF-7, and MDA-MB-361, both in mixture in vitro and after being spiked into human blood. Our multifunctional surface demonstrated highly efficient capture of tumor cells in human blood, achieving up to 82% capture efficiency (?10-fold enhancement than a surface with the antibodies alone) and up to 90% purity. Furthermore, the multipatterned antibodies allowed differential capturing of the tumor cells. These results support that our multifunctional surface has great potential as an effective platform that accommodates virtually any antibodies, which will likely lead to clinically significant, differential detection of CTCs that are rare and highly heterogeneous. PMID:24892731

  17. System for measuring multiphase flow using multiple pressure differentials

    DOEpatents

    Fincke, James R. (Idaho Falls, ID)

    2003-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Armstrong, J. T.

    2009-12-01

    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.

  19. The role of cell differentiation in controlling cell multiplication and cancer

    Microsoft Academic Search

    Karl-Hartmut von Wangenheim; Hans-Peter Peterson

    2008-01-01

    It has been suggested that cancer ought to be regarded as a disease of cell differentiation. In multicellular organisms, indeed,\\u000a the control of cell multiplication is linked to cell specialization: During the process of differentiation embryonic cells,\\u000a while cycling, acquire the ability to perform specialized functions. This ability is incompatible with cell cycling which,\\u000a as a consequence, is repressed with

  20. Multiple-Symbol Differential Detection for Space-Time Block Codes

    Microsoft Academic Search

    Chunjun Gao; A. M. Haimovich

    2002-01-01

    The loss of approximately 3 dB signal to noise ratio is always paid with conventional differential detection for space- time block code compared to the related coherent detection. In this paper, a multiple-symbol differential detection (MSDD) tech- nique is proposed for space-time block codes (STBC), which greatly reduces the performance loss by extending the observa- tion interval for decoding. The

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

    Microsoft Academic Search

    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

    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

  2. A novel differential diagnostic model for multiple primary lung cancer: Differentially-expressed gene analysis of multiple primary lung cancer and intrapulmonary metastasis

    PubMed Central

    CHEN, DALI; MEI, LONGYONG; ZHOU, YUBIN; SHEN, CHENG; XU, HUAN; NIU, ZHONGXI; CHE, GUOWEI

    2015-01-01

    The incidence of synchronous multiple primary lung cancer (MPLC) is increasing. However, present diagnostic methods are unable to satisfy the individualized treatment requirements of patients with MPLC. The present study aimed to establish a quantitative mathematical model and analyze its diagnostic value for distinguishing between MPLC and cases of the histologically similar disease, intrapulmonary metastasis (IPM). The sum value of the differential expression ratios of four proteins, namely p53, p16, p27 and c-erbB2, was evaluated by immunohistochemically-staining specimens of primary cancers, second separate cancers, metastatic lymph nodes and metastatic cancers. The sum value of the differential expression ratio of the four proteins from the primary tumor and the lymph-node metastasis or metastatic cancer was <90 in the 11 patients with a single metastatic cancer and in the 30 patients with lymph-node metastasis, but was >90 in the 14 patients with different histological types of MPLC. Therefore, a quantitative differentially-expressed gene mathematical model was established as follows: Sum of the differential expression ratios = p16T1 ? T + p27T1 ? T2 + C-erbB2T1 ? T2 + p53T1 ? T2, where T1 is the primary cancer and T2 is the lymph node metastasis, metastatic cancer or the second separate cancer. The quantitative differentially-expressed gene mathematical model is considered to be a useful tool for distinguishing between MPLC and IPM. PMID:25663860

  3. Multiple benign symmetric lipomatosis -- a differential diagnosis of obesity.

    PubMed

    Ardeleanu, V; Chicos, S; Georgescu, C; Tutunaru, D

    2013-01-01

    Benign symmetrical lipomatosis (BSL), or Madelung's disease, is a rare disease characterized by the progressive growth of diffuse, painless, non-enveloped symmetric lipomas. The etiology of this disease remains unknown, although it was associated in the medical literature with alcohol and nicotine abuse, metabolic disorders and a number of malignancies. It is assumed that there is a genetic predisposition for this affliction. The management in such cases is surgical removal of the lipomas, most times in several sessions, but this is often followed by relapse. However, surgical removal of the lipomas can provide satisfactory patient functionality and cosmetic results. The differential diagnosis is made with morbid obesity, Cushing syndrome, angiolipomatosis, encapsulated lipomas, neurofibromatosis, myxoid liposarcoma, lymphoma, salivary gland disease, Frolich and lipomatosis syndrome in patients infected with HIV. The current paper reports the case of a 55 year-old man, who presented with several large lipomatous masses, arranged symmetrically on the front and back of the trunk, and several smaller lipomas in the upper and lower limbs. Treatment consisted of resection of these lipomas in several sessions, without recurrence at one year after the last operation. PMID:23958107

  4. Sigma-2 Receptor as Potential Indicator of Stem Cell Differentiation

    PubMed Central

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

    2011-01-01

    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

  5. The neuroprotective potential of flavonoids: a multiplicity of effects

    PubMed Central

    Vauzour, David; Vafeiadou, Katerina; Rodriguez-Mateos, Ana; Rendeiro, Catarina

    2008-01-01

    Flavonoids exert a multiplicity of neuroprotective actions within the brain, including a potential to protect neurons against injury induced by neurotoxins, an ability to suppress neuroinflammation, and the potential to promote memory, learning and cognitive function. These effects appear to be underpinned by two common processes. Firstly, they interact with critical protein and lipid kinase signalling cascades in the brain leading to an inhibition of apoptosis triggered by neurotoxic species and to a promotion of neuronal survival and synaptic plasticity. Secondly, they induce beneficial effects on the vascular system leading to changes in cerebrovascular blood flow capable of causing angiogenesis, neurogenesis and changes in neuronal morphology. Through these mechanisms, the consumption of flavonoid-rich foods throughout life holds the potential to limit neurodegeneration and to prevent or reverse age-dependent loses in cognitive performance. The intense interest in the development of drugs capable of enhancing brain function means that flavonoids may represent important precursor molecules in the quest to develop of a new generation of brain enhancing drugs. PMID:18937002

  6. Medaka tert produces multiple variants with differential expression during differentiation in vitro and in vivo

    PubMed Central

    Rao, Feng; Wang, Tiansu; Li, Mingyou; Li, Zhendong; Hong, Ni; Zhao, Haobin; Yan, Yan; Lu, Wenqing; Chen, Tiansheng; Wang, Weijia; Lim, Menghuat; Yuan, Yongming; Liu, Ling; Zeng, Lingbing; Wei, Qiwei; Guan, Guijun; Li, Changming; Hong, Yunhan

    2011-01-01

    Embryonic stem (ES) cells have immortality for self-renewal and pluripotency. Differentiated human cells undergo replicative senescence. In human, the telomerase reverse transcriptase (Tert), namely the catalytic subunit of telomerase, exhibits differential expression to regulate telomerase activity governing cellular immortality or senescence, and telomerase activity or tert expression is a routine marker of pluripotent ES cells. Here we have identified the medaka tert gene and determined its expression and telomerase activity in vivo and in vitro. We found that the medaka tert locus produces five variants called terta to terte encoding isoforms TertA to TertE. The longest TertA consists of 1090 amino acid residues and displays a maximum of 34% identity to the human TERT and all the signature motifs of the Tert family. TertB to TertE are novel isoforms and have considerable truncation due to alternative splicing. The terta RNA is ubiquitous in embryos, adult tissues and cell lines, and accompanies ubiquitous telomerase activity in vivo and in vitro as revealed by TRAP assays. The tertb RNA was restricted to the testis, absent in embryos before gastrulation and barely detectable in various cell lines The tertc transcript was absent in undifferentiated ES cells but became evident upon ES cell differentiation, in vivo it was barely detectable in early embryos and became evident when embryogenesis proceeds. Therefore, ubiquitous terta expression correlates with ubiquitous telomerase activity in medaka, and expression of other tert variants appears to delineate cell differentiation in vitro and in vivo. PMID:21547060

  7. Multiple Component Event-Related Potential (mcERP) Estimation

    NASA Technical Reports Server (NTRS)

    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

    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.

  8. Differential Algebraic Birkhoff Decomposition and the renormalization of multiple zeta values

    Microsoft Academic Search

    Li Guo; Bin Zhang

    2008-01-01

    In the Hopf algebra approach of Connes and Kreimer on renormalization of quantum field theory, the renormalization process is viewed as a special case of the Algebraic Birkhoff Decomposition. We give a differential algebra variation of this decomposition and apply this to the study of multiple zeta values.

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

    ERIC Educational Resources Information Center

    Magis, David; De Boeck, Paul

    2011-01-01

    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…

  10. Computational fixed point theory for differential delay equations with multiple time lags

    E-print Network

    Lessard, Jean-Philippe

    Computational fixed point theory for differential delay equations with multiple time lags Jean nontrivial periodic solutions for a delay equation with three time lags. 1 Introduction Fixed point theory, that we describe here as computational fixed point theory, to the context of proving, in a direct

  11. Pitfalls in gastrointestinal permeability measurement in ICU patients with multiple organ failure using differential sugar absorption

    Microsoft Academic Search

    Heleen M. Oudemans-van Straaten; Peter H. J. van der Voort; Frans J. Hoek; Rob J. Bosman; Johan I. van der Spoel; Durk F. Zandstra

    2002-01-01

    Objective: To assess whether gastrointestinal permeability (GIP) at intensive care unit (ICU) admission, measured by differential sugar absorption, is related to severity of disease and multiple organ failure (MOF). Post hoc, to analyse the relation between the urinary sugar recovery and renal function. Design: Prospective observational cohort study. Setting: Eighteen-bed general ICU of a teaching hospital. Patients: Sixty-four ventilated patients

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

    NASA Technical Reports Server (NTRS)

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

    2003-01-01

    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.

  13. Differential humoral responses against heat-shock proteins after autologous stem cell transplantation in multiple myeloma.

    PubMed

    Tovar, Natalia; Fernández de Larrea, Carlos; Pedrosa, Fabiola; Aróstegui, Juan I; Cibeira, Ma Teresa; Rosińol, Laura; Elena, Montserrat; Filella, Xavier; Yagüe, Jordi; Bladé, Joan

    2014-01-01

    Heat-shock proteins (HSP) are important molecules in the pathogenesis of multiple myeloma (MM). Their blockages by drugs or cellular immune response have been investigated, and a possible association with the presence of oligoclonal bands (OB) has been postulated in patients with MM after allogenic stem cell transplantation. The aim of the present study was to ascertain the serum antibody levels against three HSP (60, 70 and 90) by ELISA in patients with MM in complete remission after autologous stem cell transplantation (ASCT), with or without OB, and compare them with those patients with stable gammopathy of undetermined significance (MGUS) and healthy controls. Our results in samples after ASCT showed no differential levels of anti-HSP according to the presence or absence of the oligoclonal response. However, higher levels of anti-HSP90 were found in patients with stable MGUS in comparison with MM patients (p?=?0.004). In the same line, a longer progression-free survival was observed in those patients who presented higher anti-HSP90 levels after ASCT (p?=?0.042). These results suggest, for first time, the potential of anti-HSP90 humoral immune response for long-term control of malignant plasma cell disorders. PMID:24218189

  14. Potentiation of retinoic acid-induced differentiation of HL-60 cells by prostaglandin EP2 receptor.

    PubMed

    Ishiguro, S; Takahashi, N; Nemoto, K; Negishi, M; Ichikawa, A

    1998-06-01

    Human promyeloid HL-60 cells are differentiated by all-trans retinoic acid (RA) to granulocytes, and prostaglandin (PG) E2 potentiates the RA-induced differentiation. Here we examined which subtype of PGE receptors was involved in this potentiating activity of PGE2. Northern blot analysis demonstrated that HL-60 cells expressed three subtypes of PGE receptor, EP2, EP3, and EP4. Among various EP agonists, and EP2-selective agonist, butaprost, preferentially potentiated the RA-induced differentiation of HL-60 cells. Butaprost not only decreased the half-maximal concentration of RA but also increased the maximal level of the differentiation. Butaprost concentration-dependently stimulated the cAMP formation, and 8-Br-cAMP strongly potentiated the RA-induced differentiation. These results demonstrate that the EP2 receptor enhances the RA-induced differentiation of HL-60 cells via stimulation of adenylate cyclase. PMID:9785384

  15. Revealing Pathway Dynamics in Heart Diseases by Analyzing Multiple Differential Networks

    PubMed Central

    Ma, Xiaoke; Gao, Long; Karamanlidis, Georgios; Gao, Peng; Lee, Chi Fung; Garcia-Menendez, Lorena; Tian, Rong; Tan, Kai

    2015-01-01

    Development of heart diseases is driven by dynamic changes in both the activity and connectivity of gene pathways. Understanding these dynamic events is critical for understanding pathogenic mechanisms and development of effective treatment. Currently, there is a lack of computational methods that enable analysis of multiple gene networks, each of which exhibits differential activity compared to the network of the baseline/healthy condition. We describe the iMDM algorithm to identify both unique and shared gene modules across multiple differential co-expression networks, termed M-DMs (multiple differential modules). We applied iMDM to a time-course RNA-Seq dataset generated using a murine heart failure model generated on two genotypes. We showed that iMDM achieves higher accuracy in inferring gene modules compared to using single or multiple co-expression networks. We found that condition-specific M-DMs exhibit differential activities, mediate different biological processes, and are enriched for genes with known cardiovascular phenotypes. By analyzing M-DMs that are present in multiple conditions, we revealed dynamic changes in pathway activity and connectivity across heart failure conditions. We further showed that module dynamics were correlated with the dynamics of disease phenotypes during the development of heart failure. Thus, pathway dynamics is a powerful measure for understanding pathogenesis. iMDM provides a principled way to dissect the dynamics of gene pathways and its relationship to the dynamics of disease phenotype. With the exponential growth of omics data, our method can aid in generating systems-level insights into disease progression. PMID:26083688

  16. A multiscale reduced-basis method for parametrized elliptic partial differential equations with multiple scales

    NASA Astrophysics Data System (ADS)

    Nguyen, N. C.

    2008-12-01

    We present a technique for solving parametrized elliptic partial differential equations with multiple scales. The technique is based on the combination of the reduced basis method [C. Prud'homme, D. Rovas, K. Veroy, Y. Maday, A.T. Patera, G. Turinici, Reliable real-time solution of parametrized partial differential equations: reduced-basis output bound methods, Journal of Fluids Engineering 124 (1) (2002) 70-80] and the multiscale finite element method [T.Y. Hou, X.H. Wu, A multiscale finite element method for elliptic problems in composite materials and porous media, Journal of Computational Physics 134 (1) (1997) 169-189] to treat problems in which the differential coefficient is characterized by a large number of independent parameters. For the multiscale finite element method, a large number of cell problems has to be solved at the fine local mesh for each new configuration of the differential coefficient. In order to improve the computational efficiency of this method, we construct reduced basis spaces that are adapted to the local parameter dependence of the differential operator. The approximate solutions of the cell problems are computed accurately and efficiently via performing Galekin projection onto the reduced basis spaces and implementing the offline-online computational procedure. Therefore, a large number of similar computations at the fine local mesh can be carried out with lower computational cost for each new configuration of the differential coefficient. Numerical results are provided to demonstrate the accuracy and efficiency of the proposed approach.

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

    NASA Technical Reports Server (NTRS)

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

    1994-01-01

    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.

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

    PubMed Central

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

    2014-01-01

    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

  19. Differentiated services with multiple random early detection algorithm using ns2 simulator

    Microsoft Academic Search

    Mohammed A. Qadeer; Vikas Sharma; Ankit Agarwal; S. S. Husain

    2009-01-01

    This paper presents an overview of random early detection algorithm and differentiated services on ns2. In the present scenario of computer networks the traffic is increasing exponentially due to which packet losses are also increasing at a great rate. An active queue management in routers and gateways can potentially reduce packet loss rates in the Internet. In this paper we

  20. Therapeutic Potential of Differentiated Mesenchymal Stem Cells for Treatment of Osteoarthritis.

    PubMed

    Ham, Onju; Lee, Chang Youn; Kim, Ran; Lee, Jihyun; Oh, Sekyung; Lee, Min Young; Kim, Jongmin; Hwang, Ki-Chul; Maeng, Lee-So; Chang, Woochul

    2015-01-01

    Osteoarthritis (OA) is a chronic, progressive, and irreversible degenerative joint disease. Conventional OA treatments often result in complications such as pain and limited activity. However, transplantation of mesenchymal stem cells (MSCs) has several beneficial effects such as paracrine effects, anti-inflammatory activity, and immunomodulatory capacity. In addition, MSCs can be differentiated into several cell types, including chondrocytes, osteocytes, endothelia, and adipocytes. Thus, transplantation of MSCs is a suggested therapeutic tool for treatment of OA. However, transplanted naďve MSCs can cause problems such as heterogeneous populations including differentiated MSCs and undifferentiated cells. To overcome this problem, new strategies for inducing differentiation of MSCs are needed. One possibility is the application of microRNA (miRNA) and small molecules, which regulate multiple molecular pathways and cellular processes such as differentiation. Here, we provide insight into possible strategies for cartilage regeneration by transplantation of differentiated MSCs to treat OA patients. PMID:26147426

  1. Comparison of methods for identifying differentially expressed genes across multiple conditions from microarray data

    PubMed Central

    Tan, Yuande; Liu, Yin

    2011-01-01

    Identification of genes differentially expressed across multiple conditions has become an important statistical problem in analyzing large-scale microarray data. Many statistical methods have been developed to address the challenging problem. Therefore, an extensive comparison among these statistical methods is extremely important for experimental scientists to choose a valid method for their data analysis. In this study, we conducted simulation studies to compare six statistical methods: the Bonferroni (B-) procedure, the Benjamini and Hochberg (BH-) procedure, the Local false discovery rate (Localfdr) method, the Optimal Discovery Procedure (ODP), the Ranking Analysis of F-statistics (RAF), and the Significant Analysis of Microarray data (SAM) in identifying differentially expressed genes. We demonstrated that the strength of treatment effect, the sample size, proportion of differentially expressed genes and variance of gene expression will significantly affect the performance of different methods. The simulated results show that ODP exhibits an extremely high power in indentifying differentially expressed genes, but significantly underestimates the False Discovery Rate (FDR) in all different data scenarios. The SAM has poor performance when the sample size is small, but is among the best-performing methods when the sample size is large. The B-procedure is stringent and thus has a low power in all data scenarios. Localfdr and RAF show comparable statistical behaviors with the BH-procedure with favorable power and conservativeness of FDR estimation. RAF performs the best when proportion of differentially expressed genes is small and treatment effect is weak, but Localfdr is better than RAF when proportion of differentially expressed genes is large. PMID:22347782

  2. Potential animal model of multiple chemical sensitivity with cholinergic supersensitivity

    Microsoft Academic Search

    David H. Overstreet; Claudia S. Miller; David S. Janowsky; Roger W. Russell

    1996-01-01

    Multiple Chemical Sensitivity (MCS) is a clinical phenomenon in which individuals, after acute or intermittent exposure to one or more chemicals, commonly organophosphate pesticides (OPs), become overly sensitive to a wide variety of chemically-unrelated compounds, which can include ethanol, caffeine and other psychotropic drugs. The Flinders Sensitive Line (FSL) rats were selectively bred to be more sensitive to the OP

  3. Phosphoproteomic analysis of kinase-deficient mice reveals multiple TAK1 targets in osteoclast differentiation.

    PubMed

    Sumiya, Eriko; Negishi-Koga, Takako; Nagai, Yusuke; Suematsu, Ayako; Suda, Tomomi; Shinohara, Masahiro; Sato, Kojiro; Sanjo, Hideki; Akira, Shizuo; Takayanagi, Hiroshi

    2015-08-01

    TAK1 (encoded by Map3k7) is a mitogen-activated protein kinase kinase kinase (MAP3K), which activates the transcription factors AP-1 and NF-?B in response to receptor activator of NF-?B ligand (RANKL) stimulation, thus constituting a key regulator of osteoclast differentiation. Here we report the functional relevance of the kinase activity of TAK1 in the late stage of osteoclast differentiation in vivo using Ctsk-Cre mice and TAK1 mutant mice in which the TAK1 kinase domain was flanked by loxP. The Map3k7(flox/kd)Ctsk(Cre/+) mice displayed a severe osteopetrotic phenotype due to a marked decrease in osteoclast number. RANKL-induced activation of MAPK and NF-?B was impaired in the late stage of osteoclast differentiation. The absence of suppressive effect of an administered NF-?B inhibitor on the late stage of osteoclastogenesis led us to investigate unknown TAK1 targets in osteoclast differentiation. We performed a phosphoproteomic analysis of RANKL-stimulated osteoclast precursor cells from Map3k7(flox/kd)Ctsk(Cre/+) mice, revealing multiple targets regulated by TAK1 during osteoclastogenesis. Thus, TAK1 functions as a critical regulator of the phosophorylation status of various cellular proteins that govern osteoclastogenesis. PMID:26102028

  4. 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 attack. Firstly, it presents the principle of CLEFIA algorithm and differential fault analysis; then fault models and corresponding analysis methods; finally, all of the fault model and analysis methods

  5. Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation

    PubMed Central

    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

    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

  6. Polar/apolar compounds induce leukemia cell differentiation by modulating cell-surface potential.

    PubMed Central

    Arcangeli, A; Carlŕ, M; Del Bene, M R; Becchetti, A; Wanke, E; Olivotto, M

    1993-01-01

    The mechanism of action of polar/apolar inducers of cell differentiation, such as dimethyl sulfoxide and hexamethylene-bisacetamide, is still obscure. In this paper evidence is provided that their effects on murine erythroleukemia cells are modulated by various extracellular cations as a precise function of the cation effects on membrane surface potential. The interfacial effects of the inducers were directly measured on the charged electrode, showing that both dimethyl sulfoxide and hexamethylene-bisacetamide, at the effective concentrations for cell differentiation and within the physiological range of charge density, adsorb at the charged surface and produce a potential shift. A linear correlation was found between this shift and the inducer effects on cell differentiation. Besides offering a different interpretation of the mechanism of action of the inducers, these findings indicate that surface potential has a signaling function. They may also be relevant to cancer treatments based on tumor-cell commitment to terminal differentiation. Images Fig. 1 PMID:8516337

  7. Multiple spacecraft rendezvous maneuvers by differential drag and low thrust engines

    NASA Astrophysics Data System (ADS)

    Bevilacqua, Riccardo; Hall, Jason S.; Romano, Marcello

    2010-01-01

    A novel two-phase hybrid controller is proposed to optimize propellant consumption during multiple spacecraft rendezvous maneuvers in Low Earth Orbit. This controller exploits generated differentials in aerodynamic drag on each involved chaser spacecraft to effect a propellant-free trajectory near to the target spacecraft during the first phase of the maneuver, and then uses a fuel optimal control strategy via continuous low-thrust engines to effect a precision dock during the second phase. In particular, by varying the imparted aerodynamic drag force on each of the chaser spacecraft, relative differential accelerations are generated between each chaser and the target spacecraft along two of the three translational degrees of freedom. In order to generate this required differential, each chaser spacecraft is assumed to include a system of rotating flat panels. Additionally, each chaser spacecraft is assumed to have continuous low-thrust capability along the three translational degrees of freedom and full-axis attitude control. Sample simulations are presented to support the validity and robustness of the proposed hybrid controller to variations in the atmospheric density along with different spacecraft masses and ballistic coefficients. Furthermore, the proposed hybrid controller is validated against a complete nonlinear orbital model to include relative navigation errors typical of carrier-phase differential GPS (CDGPS). Limitations of the proposed controller appear relative to the target spacecraft's orbit eccentricity and a general characterization of the atmospheric density. Bounds on these variables are included to provide a framework within which the proposed hybrid controller can effect an extremely low propellant rendezvous of multiple chaser spacecraft to a desired target spacecraft.

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

    PubMed

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

    2014-10-01

    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

  9. Doubly differential cross sections for single and multiple ionization of Ne by electron impact

    NASA Astrophysics Data System (ADS)

    Santos, A. C. F.; Hasan, A.; Dubois, R. D.

    2005-03-01

    We present doubly differential cross sections for single and multiple ionization of the outer shell of neon by 750eV electron impact. The distinction between single and multiple ionization was achieved by performing a charge state analysis of the recoil ions in coincidence with forward scattered, energy analyzed electrons. By a comparison to photon impact data, the contribution of the second-order double ionization mechanism is estimated and found to be neglible at this impact energy. Following a similar procedure adopted by J. A. R. Samson [Phys. Rev. Lett. 65, 2861 (1990)], the importance of the first-order TS-1 double ionization mechanism is also estimated. As a result it is found that for large energy losses shakeoff is the dominant double ionization mechanism.

  10. Diagnostic potential of plasma carboxymethyllysine and carboxyethyllysine in multiple sclerosis

    Microsoft Academic Search

    Zohara Sternberg; Cassandra Hennies; Daniel Sternberg; Ping Wang; Peter Kinkel; David Hojnacki; Bianca Weinstock-Guttmann; Frederick Munschauer

    2010-01-01

    BACKGROUND: This study compared the level of advanced glycation end products (AGEs), N-(Carboxymethyl)lysine (CML) and N-(Carboxyethyl)lysine (CEL), in patients with multiple sclerosis (MS) and healthy controls (HCs), correlating these markers with clinical indicators of MS disease severity. METHODS: CML and CEL plasma levels were analyzed in 99 MS patients and 43 HCs by tandem mass spectrometry (LC\\/MS\\/MS). Patients were stratified

  11. Potential role of daratumumab in the treatment of multiple myeloma

    PubMed Central

    Khagi, Yulian; Mark, Tomer M

    2014-01-01

    Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA), a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma. PMID:24971019

  12. Potential role of daratumumab in the treatment of multiple myeloma.

    PubMed

    Khagi, Yulian; Mark, Tomer M

    2014-01-01

    Multiple myeloma is the second most common hematologic malignancy in the US. Treatments utilizing alkylating agents, corticosteroids, proteasome inhibitors, and immunomodulatory drugs have resulted in significant survival benefits, however, despite the advances, relapse is inevitable. Decreased depth and duration of response obtained with each successive relapse of disease is typical of the disease course, thereby highlighting a continuing need for new treatment options. With the introduction of monoclonal antibodies for multiple myeloma, new options for treatment in the relapsed setting are on the horizon. Among the new immunologic agents is daratumumab (DARA), a humanized antibody to CD38 with potent multifaceted antitumor activity. Phase I and II clinical trials have demonstrated significant reduction in serum M-protein and bone marrow plasma cell percentage in refractory patients, with an acceptable toxicity profile. Moreover, ex vivo studies have shown that DARA may be particularly useful in combination with currently used anti-myeloma agents. With a recent breakthrough drug designation by the US Food and Drug Administration, DARA shows promise as mono- and combination therapy for the treatment of relapsed/refractory multiple myeloma. PMID:24971019

  13. The action as a differential n-form and the analytic deduction of the nuclear potentials

    E-print Network

    Enrique Ordaz Romay

    2003-06-17

    All the natural forces act through potential fields. Both, the electromagnetic vector potential and the gravitational potential of the general relativity are usually deduced starting from general analytic considerations. However, the nuclear potentials of the weak and strong forces are calculated experimentally, leading to what is known as phenomenological potentials. That is to say, expressions requiring adjustments according to the experimental results. This fact may change if we consider the action as a differential form. In this case it is possible to deduct some potentials for the nuclear forces departing from general analytic considerations.

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

    PubMed Central

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

    2008-01-01

    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 carnivores, 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 community of south-eastern Norway. We compared habitat selection of the brown bear Ursus arctos L., Eurasian lynx Lynx lynx L., wolf Canis lupus L. and wolverine Gulo gulo L., based on radio-tracking data. Differences in kill site locations were explored using locations of documented predator-killed sheep Ovis aries L. We modelled each species’ selection for, and differentiation in, habitat and kill sites on a landscape scale using resource selection functions and multinomial logistic regression. Based on projected probability of occurrence maps, we estimated continuous patches of habitat within the study area. Although bears, lynx, wolves and wolverines had overlapping distributions, we found a clear differentiation for all four species in both habitat and kill sites. The presence of bears, wolves and lynx was generally associated with rugged, forested areas at lower elevations, whereas wolverines selected rugged terrain at higher elevations. Some degree of sympatry was possible in over 40% of the study area, although only 1·5% could hold all four large carnivores together. Synthesis and applications. A geographically differentiated management policy has been adopted in Norway, aimed at conserving viable populations of large carnivores while minimizing the potential for conflicts. Sympatry of all four carnivores will be most successful if regional zones are established of adequate size spanning an elevational gradient. High prey densities, low carnivore densities, low dietary overlap and scavenging opportunities have most probably led to reduced competitive exclusion. Although regional sympatry enhances the conservation of an intact guild of large carnivores, it may well increase conflict levels and resistance to carnivore conservation locally. PMID:19330031

  15. Matched filtering and multiple hypothesis tracking applied to Cfiber action potentials recorded in human nerves

    E-print Network

    Matched filtering and multiple hypothesis tracking applied to C­fiber action potentials recorded, the focus is on the detection and the tracking of the nerve action potentials (APs). The subsequent data recorded in human subjects are presented. Action potentials from C­fibers were recorded

  16. A numerical method for some stochastic differential equations with multiplicative noise [rapid communication

    NASA Astrophysics Data System (ADS)

    Doering, Charles R.; Sargsyan, Khachik V.; Smereka, Peter

    2005-09-01

    Diffusion processes intended to model the continuous state space limit of birth death processes, chemical reactions, and other discrete particle systems often involve multiplicative noise where the diffusion vanishes near one (or more) of the state space boundaries. Standard direct numerical simulation schemes for the associated stochastic differential equations run the risk of “overshooting”, i.e., of varying outside the meaningful state space domain where simple analytic expressions for the diffusion coefficient may take on unphysical (negative or complex) values. We propose a simple scheme to overcome this problem and apply it to an exactly soluble stochastic ordinary differential equation (SODE), and to a related parabolic stochastic partial differential equation (SPDE) that admits exact analytic solution for the stationary correlation function. Armed with these analytic benchmark solutions, we demonstrate that the scheme produces approximate solutions for the SODE with distributions that display first-order convergence in the Wasserstein metric. For the SPDE, the scheme produces first order convergence for the stationary correlation function in L.

  17. Clinical Utility of Skin Biopsy in Differentiating between Parkinson's Disease and Multiple System Atrophy.

    PubMed

    Haga, Rie; Sugimoto, Kazuhiro; Nishijima, Haruo; Miki, Yasuo; Suzuki, Chieko; Wakabayashi, Koichi; Baba, Masayuki; Yagihashi, Soroku; Tomiyama, Masahiko

    2015-01-01

    Background. It is often difficult to differentiate Parkinson's disease (PD) from multiple system atrophy (MSA), especially in their early stages. Objectives. To examine the clinical utility of histopathological analysis of biopsied skin from the chest wall and/or leg in differentiating between the two diseases. Methods. Skin biopsies from the lower leg and/or anterior chest wall were obtained from 38 patients with idiopathic PD (26 treated with levodopa and 12 levodopa-naďve) and 13 age-matched patients with MSA. We sought aggregates of phosphorylated ?-synuclein on cutaneous nerve fibers using double fluorescence immunohistochemistry and confocal microscopy and measured intraepidermal nerve fiber density (IENFD). Results. Phosphorylated ?-synuclein aggregates were identified on cutaneous nerves in two patients with PD (5.3%) but in none of the patients with MSA, and IENFD was significantly lower in patients with PD when compared to those with MSA. There was no difference in IENFD between levodopa-treated and levodopa-naďve patients with PD. Conclusions. Our findings suggest that an assessment of IENFD in biopsied skin could be a useful means of differentiating between PD and MSA but that detection of ?-synuclein aggregates on cutaneous nerves in the distal sites of the body is insufficiently sensitive. PMID:25945280

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-10-01

    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

  20. Inelastic multiple scattering of interacting bosons in weak random potentials.

    PubMed

    Geiger, Tobias; Wellens, Thomas; Buchleitner, Andreas

    2012-07-20

    We develop a diagrammatic scattering theory for interacting bosons in a three-dimensional, weakly disordered potential. We show how collisional energy transfer between the bosons induces the thermalization of the inelastic single-particle current which, after only a few collision events, dominates over the elastic contribution described by the Gross-Pitaevskii ansatz. PMID:22861833

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

    PubMed

    Deng, Shangkun; Sakurai, Akito

    2014-01-01

    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

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

    PubMed Central

    Deng, Shangkun; Sakurai, Akito

    2014-01-01

    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

  3. Modulating mtDNA heteroplasmy by mitochondria-targeted restriction endonucleases in a ‘differential multiple cleavage-site’ model

    PubMed Central

    Bacman, SR; Williams, SL; Hernandez, D; Moraes, CT

    2009-01-01

    The ability to manipulate mitochondrial DNA (mtDNA) heteroplasmy would provide a powerful tool to treat mitochondrial diseases. Recent studies showed that mitochondria-targeted restriction endonucleases can modify mtDNA heteroplasmy in a predictable and efficient manner if it recognizes a single site in the mutant mtDNA. However, the applicability of such model is limited to mutations that create a novel cleavage site, not present in the wild-type mtDNA. We attempted to extend this approach to a ‘differential multiple cleavage site’ model, where an mtDNA mutation creates an extra restriction site to the ones normally present in the wild-type mtDNA. Taking advantage of a heteroplasmic mouse model harboring two haplotypes of mtDNA (NZB/BALB) and using adenovirus as a gene vector, we delivered a mitochondria-targeted Scal restriction endonuclease to different mouse tissues. Scal recognizes five sites in the NZB mtDNA but only three in BALB mtDNA. Our results showed that changes in mtDNA heteroplasmy were obtained by the expression of mitochondria-targeted ScaI in both liver, after intravenous injection, and in skeletal muscle, after intramuscular injection. Although mtDNA depletion was an undesirable side effect, our data suggest that under a regulated expression system, mtDNA depletion could be minimized and restriction endonucleases recognizing multiple sites could have a potential for therapeutic use. PMID:17597792

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

    NASA Astrophysics Data System (ADS)

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

    2010-12-01

    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.

  5. Current View on Osteogenic Differentiation Potential of Mesenchymal Stromal Cells Derived from Placental Tissues.

    PubMed

    Kmiecik, Gabriela; Spoldi, Valentina; Silini, Antonietta; Parolini, Ornella

    2015-08-01

    Mesenchymal stromal cells (MSC) isolated from human term placental tissues possess unique characteristics, including their peculiar immunomodulatory properties and their multilineage differentiation potential. The osteogenic differentiation capacity of placental MSC has been widely disputed, and continues to be an issue of debate. This review will briefly discuss the different MSC populations which can be obtained from different regions of human term placenta, along with their unique properties, focusing specifically on their osteogenic differentiation potential. We will present the strategies used to enhance osteogenic differentiation potential in vitro, such as through the selection of subpopulations more prone to differentiate, the modification of the components of osteo-inductive medium, and even mechanical stimulation. Accordingly, the applications of three-dimensional environments in vitro and in vivo, such as non-synthetic, polymer-based, and ceramic scaffolds, will also be discussed, along with results obtained from pre-clinical studies of placental MSC for the regeneration of bone defects and treatment of bone-related diseases. PMID:25381565

  6. Application of differential analysis of VLF signals for seismic-ionospheric precursor detection from multiple receivers

    NASA Astrophysics Data System (ADS)

    Skeberis, Christos; Zaharis, Zaharias; Xenos, Thomas; Contadakis, Michael; Stratakis, Dimitrios; Tommaso, Maggipinto; Biagi, Pier Francesco

    2015-04-01

    This study investigates the application of differential analysis on VLF signals emitted from a single transmitter and received by multiple stations in order to filter and detect disturbances that can be attributed to seismic-ionospheric precursor phenomena. The cross-correlation analysis applied on multiple VLF signals provides a way of discerning the nature of a given disturbance and accounts for more widespread geomagnetic interferences compared to local precursor phenomena. For the purpose of this paper, data acquired in Thessaloniki (40.59N, 22,78E) and in Heraklion (35.31N, 25.10E) from the VLF station in Tavolara, Italy (ICV station Lat. 40.923, Lon. 9.731) for a period of four months (September 2014 - December 2014) are used. The receivers have been developed by Elettronika Srl and are part of the International Network for Frontier Research on Earthquake Precursors (INFREP). A normalization process and an improved variant of the Hilbert-Huang transform are initially applied to the received VLF signals. The signals derived from the first two Intrinsic Mode Functions (IMF1 and IMF2) undergo a cross-correlation analysis and, in this way, time series from the two receivers can be compared. The efficacy of the processing method and the results produced by the proposed process are then discussed. Finally, results are presented along with an evaluation of the discrimination and detection capabilities of the method on disturbances of the received signals. Based upon the results, the merits of such a processing method are discussed to further improve the current method by using differential analysis to better classify between different disturbances but, more importantly, discriminate between points of interest in the provided spectra. This could provide an improved method of detecting disturbances attributed to seismic-ionospheric precursor phenomena and also contribute to a real-time method for correlating seismic activity with the observed disturbances.

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

    PubMed Central

    WANG, GUANGYE; ZHANG, XIAOHAI; YU, BAOQING; REN, KE

    2015-01-01

    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 ?g/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 morphoge-netic 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

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

    PubMed

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

    2015-07-01

    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

  9. Human Placenta-Derived CD146-Positive Mesenchymal Stromal Cells Display a Distinct Osteogenic Differentiation Potential.

    PubMed

    Ulrich, Christine; Abruzzese, Tanja; Maerz, Jan K; Ruh, Manuel; Amend, Bastian; Benz, Karin; Rolauffs, Bernd; Abele, Harald; Hart, Melanie L; Aicher, Wilhelm K

    2015-07-01

    Mesenchymal stromal cells (MSCs) are multipotent cells that can be differentiated in vitro into a variety of cell types, including adipocytes or osteoblasts. Our recent studies indicated that a high expression of CD146 on MSCs from bone marrow correlates with their robust osteogenic differentiation potential. We therefore investigated if expression of CD146 on MSCs from the placenta correlates with a similar osteogenic differentiation potential. The MSCs were isolated specifically from the endometrial and fetal parts of human term placenta and expanded in separate cultures and compared with MSCs from bone marrow as controls. The expression of cell surface antigens was investigated by flow cytometry. Differentiation of MSCs was documented by cytochemistry and analysis of typical lineage marker genes. CD146-positive MSCs were separated from CD146-negative cells by magnet-assisted cell sorts (MACS). We report that the expression of CD146 is associated with a higher osteogenic differentiation potential in human placenta-derived MSCs (pMSCs) and the CD146(pos) pMSCs generated a mineralized extracellular matrix, whereas the CD146(neg) pMSCs failed to do so. In contrast, adipogenic and chondrogenic differentiation of pMSCs was not different in CD146(pos) compared with CD146(neg) pMSCs. Upon enrichment of pMSCs by MACS, the CD146(neg) and CD146(pos) populations maintained their expression levels for this antigen for several passages in vitro. We conclude that CD146(pos) pMSCs either respond to osteogenic stimuli more vividly or, alternatively, CD146(pos) pMSCs present a pMSC subset that is predetermined to differentiate into osteoblasts. PMID:25743703

  10. Simplified NDE of multiple cracks by means of the potential drop technique

    Microsoft Academic Search

    R. Ghajarieh; M. Saka; H. Abé; I. Komura; H. Sakamoto

    1995-01-01

    A method is developed for the simplified evaluation of multiple cracks, based on the d.c. potential drop technique. A subregion containing cracks is considered. The distribution of the potential drop for the cracks except for end cracks in the subregion is measured and calculated numerically by assuming a value for the depths of the end cracks and by assuming any

  11. Crack interaction in NDE of multiple cracks by means of potential drop technique

    Microsoft Academic Search

    R. Ghajar

    2003-01-01

    A method is developed to evaluate crack interaction in NDE of multiple cracks by d.c. potential drop technique. A subregion containing m(=1,3,5,…) cracks are considered. The potential drop of the middle crack for each subregion are considered for two successive cases (m and m+2) and compared. The ratio of these two potential drops shows the effect of the first and

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

    PubMed Central

    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

    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

  13. Glioblastoma multiforme with epithelial differentiation: A potential diagnostic pitfall in cerebrospinal fluid cytology.

    PubMed

    Gill, Simpal K; Padmanabhan, Vijayalakshmi; Hickey, William F; Marotti, Jonathan D

    2015-08-01

    Cerebrospinal fluid (CSF) cytology provides valuable diagnostic and prognostic information for diseases of the central nervous system (CNS) and remains the gold standard for the detection of neoplastic meningitis. Metastatic involvement of the CSF by non-CNS neoplasms far surpasses that of primary brain tumors, although conventional glioblastoma multiforme (GBM) can occasionally be identified in the CSF. GBM with epithelial differentiation is an uncommon variant that may contain features such as adenoid structures, signet ring cells, or squamous metaplasia. Herein, we present a case of GBM with epithelial differentiation to highlight a potential diagnostic pitfall in CSF cytology. A 55-year-old man presented with neurological symptoms and a 6.4 cm left temporal lobe cystic mass. Primary resection revealed GBM with focal epithelial differentiation confirmed by cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein immunohistochemical studies. Four months following primary resection, the patient developed severe headache for which a lumbar puncture with CSF cytologic evaluation was performed. The cytospin preparation showed numerous malignant epithelioid cells with high nuclear-cytoplasmic ratio and prominent cytoplasmic vacuoles resembling metastatic carcinoma. However, the lesional cells were cytomorphologically identical to the epithelial component present in the patient's recently diagnosed GBM. This case illustrates the potential for GBM with epithelial differentiation to closely mimic metastatic carcinoma from a non-CNS site in CSF cytology, which expands the differential diagnosis and emphasizes the necessity of clinical correlation. Diagn. Cytopathol. 2015;43:638-641. © 2015 Wiley Periodicals, Inc. PMID:25913842

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

    Microsoft Academic Search

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

    2005-01-01

    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

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

    NASA Astrophysics Data System (ADS)

    Gao, Zhiqiang; Ning, Jicai; Gao, Wei

    2014-10-01

    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.

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

    PubMed

    Ryabinkin, Ilya G; Staroverov, Viktor N

    2012-10-28

    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

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

    E-print Network

    Sachin Jain

    2010-04-05

    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.

  18. DIFFERENTIAL EMISSION MEASURE ANALYSIS OF MULTIPLE STRUCTURAL COMPONENTS OF CORONAL MASS EJECTIONS IN THE INNER CORONA

    SciTech Connect

    Cheng, X.; Ding, M. D. [School of Astronomy and Space Science, Nanjing University, Nanjing 210093 (China); Zhang, J. [School of Physics, Astronomy and Computational Sciences, George Mason University, Fairfax, VA 22030 (United States); Saar, S. H., E-mail: xincheng@nju.edu.cn, E-mail: jzhang7@gmu.edu [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States)

    2012-12-10

    In this paper, we study the temperature and density properties of multiple structural components of coronal mass ejections (CMEs) using differential emission measure (DEM) analysis. The DEM analysis is based on the six-passband EUV observations of solar corona from the Atmospheric Imaging Assembly on board the Solar Dynamic Observatory. The structural components studied include the hot channel in the core region (presumably the magnetic flux rope of the CME), the bright loop-like leading front (LF), and coronal dimming in the wake of the CME. We find that the presumed flux rope has the highest average temperature (>8 MK) and density ({approx}1.0 Multiplication-Sign 10{sup 9} cm{sup -3}), resulting in an enhanced emission measure over a broad temperature range (3 {<=} T(MK) {<=} 20). On the other hand, the CME LF has a relatively cool temperature ({approx}2 MK) and a narrow temperature distribution similar to the pre-eruption coronal temperature (1 {<=} T(MK) {<=} 3). The density in the LF, however, is increased by 2%-32% compared with that of the pre-eruption corona, depending on the event and location. In coronal dimmings, the temperature is more broadly distributed (1 {<=} T(MK) {<=} 4), but the density decreases by {approx}35%-{approx}40%. These observational results show that: (1) CME core regions are significantly heated, presumably through magnetic reconnection; (2) CME LFs are a consequence of compression of ambient plasma caused by the expansion of the CME core region; and (3) the dimmings are largely caused by the plasma rarefaction associated with the eruption.

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

    PubMed

    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

    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

  20. Periventricular Lesions Help Differentiate Neuromyelitis Optica Spectrum Disorders from Multiple Sclerosis

    PubMed Central

    Loh, John P.; Saba, Luca; Omari, Mirza; Herbert, Joseph; Kister, Ilya

    2014-01-01

    Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered (“type A”) or jagged-bordered (“type B”) pattern. On sagittal FLAIR, the images were evaluated for presence of “Dawson's fingers.” Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and “jagged-bordered” periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases. PMID:24665366

  1. Differentially regulated GPVI ectodomain shedding by multiple platelet-expressed proteinases.

    PubMed

    Bender, Markus; Hofmann, Sebastian; Stegner, David; Chalaris, Athena; Bösl, Michael; Braun, Attila; Scheller, Jürgen; Rose-John, Stefan; Nieswandt, Bernhard

    2010-10-28

    Glycoprotein VI (GPVI) mediates platelet activation on exposed subendothelial collagens at sites of vascular injury and thereby contributes to normal hemostasis, but also to the occlusion of diseased vessels in the setting of myocardial infarction or stroke. GPVI is an attractive target for antithrombotic therapy, particularly because previous studies have shown that anti-GPVI antibodies induce irreversible down-regulation of the receptor in circulating platelets by internalization and/or ectodomain shedding. Metalloproteinases of the a disintegrin and metalloproteinase (ADAM) family have been proposed to mediate this ectodomain shedding, but direct evidence for this is lacking. Here, we studied GPVI shedding in vitro and in vivo in newly generated mice with a megakaryocyte-specific ADAM10 deficiency and in Adam17(ex/ex) mice, which lack functional ADAM17. We demonstrate that GPVI cleavage in vitro can occur independently through either ADAM10 or ADAM17 in response to distinct stimuli. In contrast, antibody (JAQ1)-induced GPVI shedding in vivo occurred in mice lacking both ADAM10/ADAM17 in their platelets, suggesting the existence of a third GPVI cleaving platelet enzyme. This was supported by in vitro studies on ADAM10/ADAM17 double-deficient platelets. These results reveal that ectodomain shedding of GPVI can be mediated through multiple differentially regulated platelet-expressed proteinases with obvious therapeutic implications. PMID:20644114

  2. Differentiation stage determines potential of hematopoietic cells for reprogramming into induced pluripotent stem cells

    Microsoft Academic Search

    Sarah Eminli; Adlen Foudi; Matthias Stadtfeld; Nimet Maherali; Tim Ahfeldt; Gustavo Mostoslavsky; Hanno Hock; Konrad Hochedlinger

    2009-01-01

    The reprogramming of somatic cells into induced pluripotent stem (iPS) cells upon overexpression of the transcription factors Oct4, Sox2, Klf4 and cMyc is inefficient. It has been assumed that the somatic differentiation state provides a barrier for efficient reprogramming; however, direct evidence for this notion is lacking. Here, we tested the potential of mouse hematopoietic cells at different stages of

  3. Differentiating cerebellar and brainstem lesions with ocular vestibular-evoked myogenic potential test

    Microsoft Academic Search

    Chia-Hung Su; Yi-Ho Young

    2011-01-01

    This study applied both ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests in patients with\\u000a cerebellar disorders to determine whether VEMP test can differentiate between cerebellar and brainstem lesions. A total of\\u000a 12 patients with cerebellar disorder, including extended cerebellar lesion (involving the brainstem) in 8 and localized cerebellar\\u000a lesion (excluding the brainstem) in 4, were enrolled in

  4. Epigenetic Signatures Associated with Different Levels of Differentiation Potential in Human Stem Cells

    Microsoft Academic Search

    Pablo Aranda; Xabier Agirre; Esteban Ballestar; Enrique J. Andreu; José Román-Gómez; Inés Prieto; José Ignacio Martín-Subero; Juan Cruz Cigudosa; Reiner Siebert; Manel Esteller; Felipe Prosper

    2009-01-01

    BackgroundThe therapeutic use of multipotent stem cells depends on their differentiation potential, which has been shown to be variable for different populations. These differences are likely to be the result of key changes in their epigenetic profiles.Methodology\\/Principal Findingsto address this issue, we have investigated the levels of epigenetic regulation in well characterized populations of pluripotent embryonic stem cells (ESC) and

  5. Measurement of multiple-site cracking in simulated aircraft panels using AC potential drop

    SciTech Connect

    Jablonski, D.A. [Instron Corp., Canton, MA (United States)

    1995-04-01

    The characterization of multiple-site damage by use of laboratory test specimens is an important precursor to the understanding of multiple-site damage in aging aircraft. As the number of damage sites in the laboratory specimen increases, it becomes more time-consuming to measure crack initiation and growth from the various sites. Typically the crack initiation and crack growth would be measured either visually or with a low-power microscope. This technique is accurate, but it is labor-intensive. To decrease the time necessary to obtain multiple-site crack growth rate data, an automated crack length measuring technique, AC potential drop, was investigated. This AC potential drop technique was applied to aluminum test specimens under fatigue cycling conditions as well as monotonic R-curve testing. Aluminum ALCLAD 2024 test specimens of three different specimen geometries were examined. Specimens with a single-hole were used to examine the effects of lead placement on the sensitivity of AC potential drop. Three-hole specimens were used to simulate multiple-site cracking from several holes. Riveted specimens containing one row of three rivets were used to examine multiple-site cracking from fasteners. Optimum current and potential lead geometries were determined for each specimen geometry. Relationships between the AC potential and crack length were determined for AC current frequencies of 3, 10, and 30 kHz. The sensitivity of AC potential drop in measuring crack initiation was investigated. The sensitivity was found to increase substantially with increasing AC current frequency.

  6. Computational Studies of Multiple-Particle Nonlinear Dynamics in a Spatio-Temporally periodic potential

    E-print Network

    Owen D. Myers; Junru Wu; Jeffrey S. Marshall; Christopher M. Danforth

    2014-09-03

    The spatio-temporally periodic (STP) potential is interesting in Physics due to the intimate coupling between its time and spatial components. In this paper we begin with a brief discussion of the dynamical behaviors of a single particle in a STP potential and then examine the dynamics of multiple particles interacting in a STP potential via the electric Coulomb potential. For the multiple particle case, we focus on the occurrence of bifurcations when the amplitude of the STP potential varies. It is found that the particle concentration of the system plays an important role; the type of bifurcations that occur and the number of attractors present in the Poincar\\'e sections depend on whether the number of particles in the simulation is even or odd. In addition to the nonlinear dynamical approach we also discuss dependence of the squared fractional deviation of particles kinetic energy of the multiple particle system on the amplitude of the STP potential which can be used to elucidate certain transitions of states; this approach is simple and useful particularly for experimental studies of complicated interacting systems.

  7. Multiscale renormalization group methods for effective potentials with multiple scalar fields

    NASA Astrophysics Data System (ADS)

    Steele, T. G.; Wang, Zhi-Wei; McKeon, D. G. C.

    2014-11-01

    Multiscale renormalization group (RG) methods are reviewed and applied to the analysis of the effective potential for radiative symmetry breaking with multiple scalar fields, allowing an extension of the Gildener and Weinberg method beyond the weak coupling limit. A model containing two interacting real scalar fields is used to illustrate multiscale RG methods and the multiscale RG functions of this model are calculated to one-loop order for the ? function and two-loop order for the anomalous mass dimension. The introduction of an extra renormalization scale allows the mapping of the effective potential in this model onto a RG-equivalent form with an O (2 ) symmetric structure along a particular trajectory in the multiple renormalization-scale space, leading to a simplified form of the effective potential. It is demonstrated that the physical content of the effective potential in the original model, referenced to a single conventional renormalization scale, can be extracted from a particular RG trajectory that connects to this multiscale O (2 )-symmetric form of the effective potential. Extensions of these multiscale methods for effective potentials in models containing multiple scalars with O (M )×O (N ) symmetry are also discussed.

  8. The New Principle Of Sensor Differentiation By Electric Potential Bias In Metal Oxide Sensor Arrays

    NASA Astrophysics Data System (ADS)

    Kiselev, I.; Sommer, M.; Sysoev, V. V.

    2009-05-01

    We present a new method to differentiate the response of individual sensors in a metal oxide gas sensor array of E-nose type by application of varied electric potential biases and discuss how to employ the spatially distributed potential as a gas recognition pattern. The method is based on the impact, which the electric potential has upon the thermodynamic state of the metal oxide surface and on the gas adsorption processes. It is shown that the utilization of varied electric potentials yields a significant gas recognition power of E-nose, similar or even higher compared to the effect of conventional spatial temperature gradient differentiation. One advantage to use the potential distribution is the opportunity to have the whole continuous film as a sensor field, which would eliminate the influence of electrodes. The tests of a prototype of the multisensor array based on the considered method have shown its feasibility for getting high gas recognition and the capability to discriminate gas concentrations reliably.

  9. The potential for ill-posedness of multiplication operators occurring in inverse problems

    E-print Network

    The potential for ill-posedness of multiplication operators occurring in inverse problems Bernd mapping in L2(0, 1) occurring in linear ill-posed operator equations and in the linearization of nonlinear ill-posed operator equations with compact forward operators. We give examples of nonlinear inverse

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

    NSDL National Science Digital Library

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

    2006-01-01

    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.

  11. Multiplication

    NSDL National Science Digital Library

    Ms.Roberts

    2009-02-24

    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! ...

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

    SciTech Connect

    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

    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.

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

    PubMed

    Salamon, Achim; Jonitz-Heincke, Anika; Adam, Stefanie; Rychly, Joachim; Müller-Hilke, Brigitte; Bader, Rainer; Lochner, Katrin; Peters, Kirsten

    2013-11-01

    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. PMID:24055981

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

    PubMed Central

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

    2008-01-01

    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

  15. Detection of Olfactory Dysfunction Using Olfactory Event Related Potentials in Young Patients with Multiple Sclerosis

    PubMed Central

    Caminiti, Fabrizia; De Salvo, Simona; De Cola, Maria Cristina; Russo, Margherita; Bramanti, Placido; Marino, Silvia; Ciurleo, Rosella

    2014-01-01

    Background Several studies reported olfactory dysfunction in patients with multiple sclerosis. The estimate of the incidence of olfactory deficits in multiple sclerosis is uncertain; this may arise from different testing methods that may be influenced by patients' response bias and clinical, demographic and cognitive features. Aims To evaluate objectively the olfactory function using Olfactory Event Related Potentials. Materials and Methods We tested the olfactory function of 30 patients with relapsing remitting multiple sclerosis (mean age of 36.03±6.96 years) and of 30 age, sex and smoking–habit matched healthy controls by using olfactory potentials. A selective and controlled stimulation of the olfactory system to elicit the olfactory event related potentials was achieved by a computer-controlled olfactometer linked directly with electroencephalograph. Relationships between olfactory potential results and patients' clinical characteristics, such as gender, disability status score, disease-modifying therapy, and disease duration, were evaluated. Results Seven of 30 patients did not show olfactory event related potentials. Sixteen of remaining 23 patients had a mean value of amplitude significantly lower than control group (p<0.01). The presence/absence of olfactory event related potentials was associated with dichotomous expanded disability status scale (p?=?0.0433), as well as inversely correlated with the disease duration (r?=??0.3641, p?=?0.0479). Conclusion Unbiased olfactory dysfunction of different severity found in multiple sclerosis patients suggests an organic impairment which could be related to neuroinflammatory and/or neurodegenerative processes of olfactory networks, supporting the recent findings on neurophysiopathology of disease. PMID:25047369

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

    E-print Network

    D. L. Foulis

    2008-06-03

    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.

  17. A cost-effective differential mobility analyzer (cDMA) for multiple DMA column applications

    SciTech Connect

    Mei, F.; Fu, H.; Chen, D.-R.

    2011-05-04

    In aerosol research and applications, a differential mobility analyzer (DMA) is now considered the standard tool for sizing and classifying monodisperse particles in the sub-micrometer and nanometer size ranges. However, DMA application at the pilot or industrial production scale remains infeasible because of the low mass throughput. A simple way to scale up DMA operation is to use multiple DMA columns. The manufacture and maintenance costs of existing DMAs, however, limit such a scale-up. A cost-effective DMA column (named cDMA) has thus been developed in this work to address the above issue. To reduce its manufacturing cost, the prototype was constructed using parts requiring little machining. The cDMA column was also designed for easy maintenance and easy variation of the classification length for any application-specified size range. In this study, prototypes with two particle classification lengths, 1.75 and 4.50 cm, were constructed and their performance was experimentally evaluated at sheath-to-aerosol flowrate ratios of 5:1, 10:1, and 15:1 via the tandem DMA (TDMA) technique. It was concluded that both prototype cDMAs, operated at a sheath/aerosol flowrate ratio less than 15:1 and with a polydisperse aerosol flowrate of 1.0 lpm, achieved sizing resolution comparable to that offered by Nano-DMA. The longer cDMA had comparable transmission efficiency to that of Nano-DMA, and the shorter cDMA exceeded the performance of Nano-DMA. Hence, the cDMA with the shorter (1.75 cm) classification length is better suited for the characterization of macromolecular samples.

  18. A differential scanning calorimetry study on poly(ethylene terephthalate) isothermally crystallized at stepwise temperatures: multiple melting behavior re-investigated

    Microsoft Academic Search

    E. M. Woo; T. Y. Ko

    1996-01-01

    The multiple melting behavior of poly(ethylene terephthalate) (PET) was investigated with differential scanning calorimetry (DSC) by examining PET samples having been subjected to special schemes of crystallization and annealing treatment at multiple descending temperatures. Upon such step-wise annealing in decreasing temperatures, the existence of doublet melting peaks in addition to a series of multiple minor peaks in the PET has

  19. Mesenchymal stromal cells revert multiple myeloma cells to less differentiated phenotype by the combined activities of adhesive interactions and interleukin-6

    Microsoft Academic Search

    Nili Dezorella; Meirav Pevsner-Fischer; Varda Deutsch; Sigi Kay; Shoshana Baron; Ruth Stern; Sigal Tavor; Arnon Nagler; Elizabeth Naparstek; Dov Zipori; Ben-Zion Katz

    2009-01-01

    Multiple myeloma is characterized by the malignant growth of immunoglobulin producing plasma cells, predominantly in the bone marrow. The effects of primary human mesenchymal stromal cells on the differentiation phenotype of multiple myeloma cells were studied by co-culture experiments. The incubation of multiple myeloma cells with bone marrow-derived mesenchymal stromal cells resulted in significant reduction of the expression of the

  20. Initiator of carcinogenesis selectively and stably inhibits stem cell differentiation: a concept that initiation of carcinogenesis involves multiple phases

    SciTech Connect

    Scott, R.E.; Maercklein, P.B.

    1985-05-01

    A concept of carcinogenesis was recently devised in our laboratory that suggests the development of defects in the control of cell differentiation is associated with an early phase of carcinogenesis. To test this proposal directly, the effects of an initiator of carcinogenesis (i.e., UV irradiation) on proadipocyte stem cell differentiation and proliferation was assayed. In this regard, 3T3 T proadipocytes represent a nontransformed mesenchymal stem cell line that possesses the ability to regulate its differentiation at a distinct state in the G1 phase of the cell cycle as well as the ability to regulate its proliferation at two additional G1 states. The results establish that a slow dosage of 254 nm UV irradiation selectivity and stably inhibits the differentiation of a high percentage of proadipocyte stem cells without significantly altering their ability to regulate cellular proliferation in growth factor-deficient or nutrient-deficient culture conditions. Differentiation-defect proadipocyte stem cells are demonstrated not to be completely transformed but to show an increased spontaneous transformation rate, as evidenced by the formation of type III foci in high density cell cultures. These data support the role of defects in the control of differentiation in the inhibition of carcinogenesis. These observations support a concept that the initiation of carcinogenesis involves multiple phases.

  1. Dimension, multiplicity, holonomic modules, and an analogue of the inequality of Bernstein for rings of differential operators in prime characteristic

    Microsoft Academic Search

    V. V. Bavula

    2006-01-01

    Let $K$ be an {\\\\em arbitrary} field of characteristic $p>0$ and $\\\\CD (P_n)$ be the ring of differential operators on a polynomial algebra $P_n$ in $n$ variables. A long anticipated {\\\\em analogue of the inequality of Bernstein} is proved for the ring $\\\\CD (P_n)$. On the way, analogues of the concepts of (Gelfand-Kirillov) {\\\\em dimension, multiplicity, holonomic modules} are found

  2. Simultaneous measurement of phosphorus and carbon uptake in Lake Kinneret by multiple isotopic labeling and differential filtration

    Microsoft Academic Search

    T. Berman; M. Stiller

    1977-01-01

    Differential filtration and multiple isotopic labeling were combined to study the uptake of [14C]bicarbonate, [14C]glucose, and [32P]orthophosphate by microplakton in Lake Kinneret, Israel. Short-term (4 hr) uptake experiments showed seasonal changes in the size distributions of organisms taking up inorganic carbon, glucose carbon, and orthophosphate in the lake water. In a time-course experiment of 48 hr (Jan 1976) most, but

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

    PubMed Central

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

    2014-01-01

    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

  4. Differential modulation of phasic and tonic inhibition underlies serotonergic suppression of long-term potentiation in the rat visual cortex.

    PubMed

    Jang, H-J; Cho, K-H; Joo, K; Kim, M-J; Rhie, D-J

    2015-08-20

    GABA receptor type A (GABAAR)-mediated inhibition is divided into phasic and tonic inhibition. GABAARs mediating the two inhibitory modalities exhibit differences in subcellular localization and subunit composition. We previously demonstrated that phasic and tonic inhibition are independently regulated by Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) and protein kinase A (PKA), respectively. Since modulation of GABAARs by phosphorylation differs depending on subunit composition and protein kinases, phasic and tonic inhibition might be differentially regulated by a single neuromodulator activating multiple protein kinases. However, the neuromodulatory control for phasic and tonic inhibition is largely unknown. Thus, in the present study, we concurrently investigated the serotonin (5-HT) regulation of phasic and tonic inhibition and its functional implication in the pyramidal neurons of the rat visual cortex. Interestingly, 5-HT enhanced phasic inhibition but suppressed tonic inhibition. Increase in phasic inhibition was mediated by 5-HT2 receptor and CaMKII, whereas decrease in tonic inhibition depended on 5-HT1A receptor and PKA. Thus, phasic and tonic inhibition might be independently regulated even by a single neuromodulator. Functionally, the opposite modulation of phasic and tonic inhibition decreased the summation of consecutive excitatory postsynaptic potentials (EPSPs) without affecting the shape of single EPSPs, which might underlie the suppression of the induction of long-term potentiation by 5-HT. These results suggest that the integrative regulation of phasic and tonic inhibition provides mechanisms for elaborate modulation of shape and summation of EPSPs and long-term synaptic plasticity. PMID:26086544

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

    SciTech Connect

    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

    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.

  6. Benchmarking in a differentially heated rotating annulus experiment: Multiple equilibria in the light of laboratory experiments and simulations

    NASA Astrophysics Data System (ADS)

    Vincze, Miklos; Harlander, Uwe; Borchert, Sebastian; Achatz, Ulrich; Baumann, Martin; Egbers, Christoph; Fröhlich, Jochen; Hertel, Claudia; Heuveline, Vincent; Hickel, Stefan; von Larcher, Thomas; Remmler, Sebastian

    2014-05-01

    In the framework of the German Science Foundation's (DFG) priority program 'MetStröm' various laboratory experiments have been carried out in a differentially heated rotating annulus configuration in order to test, validate and tune numerical methods to be used for modeling large-scale atmospheric processes. This classic experimental set-up is well known since the late 1940s and is a widely studied minimal model of the general mid-latitude atmospheric circulation. The two most relevant factors of cyclogenesis, namely rotation and meridional temperature gradient are quite well captured in this simple arrangement. The tabletop-size rotating tank is divided into three sections by coaxial cylindrical sidewalls. The innermost section is cooled whereas the outermost annular cavity is heated, therefore the working fluid (de-ionized water) in the middle annular section experiences differential heat flow, which imposes thermal (density) stratification on the fluid. At high enough rotation rates the isothermal surfaces tilt, leading to baroclinic instability. The extra potential energy stored in this unstable configuration is then converted into kinetic energy, exciting drifting wave patterns of temperature and momentum anomalies. The signatures of these baroclinic waves at the free water surface have been analysed via infrared thermography in a wide range of rotation rates (keeping the radial temperature difference constant) and under different initial conditions (namely, initial spin-up and "spin-down"). Paralelly to the laboratory simulations of BTU Cottbus-Senftenberg, five other groups from the MetStröm collaboration have conducted simulations in the same parameter regime using different numerical approaches and solvers, and applying different initial conditions and perturbations for stability analysis. The obtained baroclinic wave patterns have been evaluated via determining and comparing their Empirical Orthogonal Functions (EOFs), drift rates and dominant wave modes. Thus certain "benchmarks" have been created that can later be used as test cases for atmospheric numerical model validation. Both in the experiments and in the numerics multiple equilibrium states have been observed in the form of hysteretic behavior depending on the initial conditions. The precise quantification of these state and wave mode transitions may shed light to some aspects of the basic underlying dynamics of the baroclinic annulus configuration, still to be understood.

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

    PubMed Central

    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

    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

  8. Visual and motor evoked potentials in the course of multiple sclerosis.

    PubMed

    Fuhr, P; Borggrefe-Chappuis, A; Schindler, C; Kappos, L

    2001-11-01

    While evoked potentials are sensitive tools for diagnosing multiple sclerosis, little is known about their prognostic value and their role in determining the course of the disease. To validate the visual and motor evoked potentials (VEP and MEP) as measures for the course of multiple sclerosis, we examined prospectively 30 patients with relapsing-remitting or secondary progressive multiple sclerosis. The Expanded Disability Status Scale (EDSS), VEP and MEP were measured at entry and after 6, 12 and 24 months. The Spearman rank correlation was used for statistical analysis. Applying multiple regression in 15 randomized patients allowed derivation of a formula for predicting changes in EDSS score based on changes in MEP and VEP. Validation was done by comparing the predicted with the real changes in EDSS in the other 15 patients. The number of pathological VEP and MEP results correlated at all four measurement points with the EDSS (rho > or = 0.6, P < or = 0.01). When the latencies of VEP and MEP were combined using the sum of their Z scores, correlation with the EDSS was even more significant (rho > or = 0.6, P < 0.001). Changes over time of electrophysiological data and EDSS were also correlated (rho = 0.43, P < 0.05). Moreover, VEP and MEP at baseline correlated with the EDSS after 2 years (rho = 0.43,P = 0.03). Reliable prediction of the course of multiple sclerosis for individual patients is not possible from VEP and MEP data. However, we conclude that, for groups of patients with secondary progressive or relapsing-remitting multiple sclerosis the combined testing of VEP and MEP yields numerical data that allow objective estimation of the course and prognosis of the disease. PMID:11673318

  9. Genetic-algorithm implementation of atomic potential reconstruction from differential electron scattering cross sections

    SciTech Connect

    Xu Junliang; Chen Zhangjin; Lin, C. D. [Department of Physics, Cardwell Hall, Kansas State University, Manhattan, Kansas 66506 (United States); Zhou Hsiaoling [Department of Physics and Astronomy, Georgia State University, Atlanta, Georgia 30303 (United States)

    2009-05-15

    We demonstrate the successful implementation of genetic algorithm for the retrieval of atomic potentials using elastic differential cross sections (DCSs) between free electrons and atomic ions for electron energies from a few to several tens of electron volts. Since the DCSs over this energy region can be extracted from laser-generated high-energy photoelectron momentum spectra, the results suggest that infrared lasers can be used to image the target structure. Extending to molecular targets, in particular, to transient molecules created by an earlier pump pulse, our results suggest that few-cycle infrared probe lasers can be used for dynamic chemical imaging with temporal resolution of a few femtoseconds.

  10. Distinct Stem Cells Subpopulations Isolated from Human Adipose Tissue Exhibit Different Chondrogenic and Osteogenic Differentiation Potential

    Microsoft Academic Search

    Tommaso Rada; Rui L. Reis; Manuela E. Gomes

    2011-01-01

    Recently adipose tissue has become a research topic also for the\\u000d\\u000a searching for an alternative stem cells source to use in cell based\\u000d\\u000a therapies such as tissue engineer. In fact Adipose Stem Cells (ASCs)\\u000d\\u000a exhibit an important differentiation potential for several cell lineages\\u000d\\u000a such as chondrogenic, osteogenic, myogenic, adipogenic and endothelial\\u000d\\u000a cells. ASCs populations isolated using standard methodologies (i.e.,\\u000d\\u000a based

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

    E-print Network

    Boyer, Edmond

    to differentiate when maintained in a medium containing fetal calf or rabbit serum. In contrast, differentiation cells of the preadipocyte clonal line Obl7) grown and/or maintained in serum-free hormone to growth hormone (GH) and triiodothyronine (Tg), fetuin, a bovine fetal protein (also present at high

  12. Mechanisms involved in differential conduction of potentials at high frequency in a branching axon.

    PubMed Central

    Grossman, Y; Parnas, I; Spira, M E

    1979-01-01

    1. The ionic mechanisms involved in block of conduction of action potentials following high frequency stimulation were studied in a branching axon of the lobster Panulirus penicillatus. 2. A 2-3 mM increase in extracellular K concentration (normal concentration 12 mM) produced block of conduction into both daughter branches. 3. While conduction block induced by high frequency stimulation occurs first into the large daughter branch and only later into the smaller one, propagation into both branches is blocked simultaneously by increased extracellular K concentration. 4. Increasing extracellular K by 2-3 mM resulted in membrane depolarization, reduction in membrane resistance and reduced excitability. The latter two effects were larger than expected from the small depolarization. It appears that increase of extracellular K has direct effects on membrane excitability. 5. It is suggested that block of conduction after high frequency stimulation results from accumulation of K in the extracellular space. However, in order to account for differential conduction block in the two branches one must assume differential buildup of extracellular K concentration around the two branches during high frequency stimulation. 6. Ultrastructural studies using La and horseradish peroxidase as extracellular markers show that the space around the two branches is similar and is open to the extracellular space. Therefore differences in periaxonal volume cannot account for differential buildup of K around the two branches. 7. It is demonstrated that the lobster axon has a Na+/K+ electrogenic pump. After blocking this pump with ouabain, stimulation at high frequency resulted in a conduction block in the two branches almost at the same time. 8. Injection of Ca2+ intracellularly into the thick branch prevents or delays the appearance of conduction block after high frequency stimulation. 9. A mechanism based on these findings is suggested to explain the differential conduction block seen after high frequency stimulation in a branching axon with almost ideal impedance matching. Images A B C A B C D PMID:521940

  13. Mechanisms involved in differential conduction of potentials at high frequency in a branching axon.

    PubMed

    Grossman, Y; Parnas, I; Spira, M E

    1979-10-01

    1. The ionic mechanisms involved in block of conduction of action potentials following high frequency stimulation were studied in a branching axon of the lobster Panulirus penicillatus. 2. A 2-3 mM increase in extracellular K concentration (normal concentration 12 mM) produced block of conduction into both daughter branches. 3. While conduction block induced by high frequency stimulation occurs first into the large daughter branch and only later into the smaller one, propagation into both branches is blocked simultaneously by increased extracellular K concentration. 4. Increasing extracellular K by 2-3 mM resulted in membrane depolarization, reduction in membrane resistance and reduced excitability. The latter two effects were larger than expected from the small depolarization. It appears that increase of extracellular K has direct effects on membrane excitability. 5. It is suggested that block of conduction after high frequency stimulation results from accumulation of K in the extracellular space. However, in order to account for differential conduction block in the two branches one must assume differential buildup of extracellular K concentration around the two branches during high frequency stimulation. 6. Ultrastructural studies using La and horseradish peroxidase as extracellular markers show that the space around the two branches is similar and is open to the extracellular space. Therefore differences in periaxonal volume cannot account for differential buildup of K around the two branches. 7. It is demonstrated that the lobster axon has a Na+/K+ electrogenic pump. After blocking this pump with ouabain, stimulation at high frequency resulted in a conduction block in the two branches almost at the same time. 8. Injection of Ca2+ intracellularly into the thick branch prevents or delays the appearance of conduction block after high frequency stimulation. 9. A mechanism based on these findings is suggested to explain the differential conduction block seen after high frequency stimulation in a branching axon with almost ideal impedance matching. PMID:521940

  14. Functional Relationships between Genes Associated with Differentiation Potential of Aged Myogenic Progenitors

    PubMed Central

    Nagarajan, Radhakrishnan; Datta, Sujay; Scutari, Marco; Beggs, Marjorie L.; Nolen, Greg T.; Peterson, Charlotte A.

    2010-01-01

    Aging is accompanied by considerable heterogeneity with possible co-expression of differentiation pathways. The present study investigates the interplay between crucial myogenic, adipogenic, and Wnt-related genes orchestrating aged myogenic progenitor differentiation (AMPD) using clonal gene expression profiling in conjunction with Bayesian structure learning (BSL) techniques. The expression of three myogenic regulatory factor genes (Myogenin, Myf-5, MyoD1), four genes involved in regulating adipogenic potential (C/EBP?, DDIT3, FoxC2, PPAR?), and two genes in the Wnt signaling pathway (Lrp5, Wnt5a) known to influence both differentiation programs were determined across 34 clones by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Three control genes were used for normalization of the clonal expression data (18S, GAPDH, and B2M). Constraint-based BSL techniques, namely (a) PC Algorithm, (b) Grow-shrink (GS) algorithm, and (c) Incremental Association Markov Blanket (IAMB) were used to model the functional relationships (FRs) in the form of acyclic networks from the clonal expression profiles. A novel resampling approach that obviates the need for a user-defined confidence threshold is proposed to identify statistically significant FRs at small sample sizes. Interestingly, the resulting acyclic network consisted of FRs corresponding to myogenic, adipogenic, Wnt-related genes and their interaction. A significant number of these FRs were robust to normalization across the three house-keeping genes and the choice of the BSL technique. The results presented elucidate the delicate balance between differentiation pathways (i.e., myogenic as well as adipogenic) and possible cross-talk between pathways in AMPD. PMID:21423363

  15. Identification of a potential tumor differentiation factor receptor candidate in prostate cancer cells.

    PubMed

    Sokolowska, Izabela; Woods, Alisa G; Gawinowicz, Mary Ann; Roy, Urmi; Darie, Costel C

    2012-07-01

    Tumor differentiation factor (TDF) is a pituitary protein that is secreted into the bloodstream and has an endocrine function. TDF and TDF-P1, a 20-residue peptide selected from the ORF of TDF, induce differentiation in human breast and prostate cancer cells, but not in other cells. TDF has no known mechanism of action. In our recent study, we identified heat shock 70 kDa proteins (HSP70s) as TDF receptors (TDF-Rs) in breast cancer cells. Therefore, we sought to investigate whether TDF-R candidates from prostate cancer cells are the same as those identified in breast cancer cells. Here, we used TDF-P1 to purify the potential TDF-R candidates by affinity purification chromatography from DU145 and PC3 steroid-resistant prostate cancer cells, LNCaP steroid-responsive prostate cancer cells, and nonprostate NG108 neuroblastoma and BLK CL.4 fibroblast-like cells. We identified the purified proteins by MS, and validated them by western blotting, immunofluorescence microscopy, immunoaffinity purification chromatography, and structural biology. We identified seven candidate proteins, of which three were from the HSP70 family. These three proteins were validated as potential TDF-R candidates in LNCaP steroid-responsive and in DU145 and PC3 steroid-resistant prostate cancer cells, but not in NG108 neuroblastoma and BLK CL.4 fibroblast-like cells. Our previous study and the current study suggest that GRP78, and perhaps HSP70s, are strong TDF-R candidates, and further suggest that TDF interacts with its receptors exclusively in breast and prostate cells, inducing cell differentiation through a novel, steroid-independent pathway. PMID:22613557

  16. Multiplication

    NSDL National Science Digital Library

    Ms. Walker

    2008-03-26

    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 ...

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

    SciTech Connect

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

    2013-01-01

    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.

  18. Relay Selection Based Double-Differential Transmission for Cooperative Networks with Multiple Carrier Frequency Offsets: Model, Analysis, and Optimization

    NASA Astrophysics Data System (ADS)

    Zhao, Kun; Zhang, Bangning; Pan, Kegang; Liu, Aijun; Guo, Daoxing

    2014-07-01

    Due to the distributed nature, cooperative networks are generally subject to multiple carrier frequency offsets (MCFOs), which make the channels time-varying and drastically degrade the system performance. In this paper, to address the MCFOs problem in detect-andforward (DetF) multi-relay cooperative networks, a robust relay selection (RS) based double-differential (DD) transmission scheme, termed RSDDT, is proposed, where the best relay is selected to forward the source's double-differentially modulated signals to the destination with the DetF protocol. The proposed RSDDT scheme can achieve excellent performance over fading channels in the presence of unknown MCFOs. Considering double-differential multiple phase-shift keying (DDMPSK) is applied, we first derive exact expressions for the outage probability and average bit error rate (BER) of the RSDDT scheme. Then, we look into the high signal-to-noise ratio (SNR) regime and present simple and informative asymptotic outage probability and average BER expressions, which reveal that the proposed scheme can achieve full diversity. Moreover, to further improve the BER performance of the RSDDT scheme, we investigate the optimum power allocation strategy among the source and the relay nodes, and simple analytical solutions are obtained. Numerical results are provided to corroborate the derived analytical expressions and it is demonstrated that the proposed optimum power allocation strategy offers substantial BER performance improvement over the equal power allocation strategy.

  19. Novel SCRG1/BST1 axis regulates self-renewal, migration, and osteogenic differentiation potential in mesenchymal stem cells

    PubMed Central

    Aomatsu, Emiko; Takahashi, Noriko; Sawada, Shunsuke; Okubo, Naoto; Hasegawa, Tomokazu; Taira, Masayuki; Miura, Hiroyuki; Ishisaki, Akira; Chosa, Naoyuki

    2014-01-01

    Human mesenchymal stem cells (hMSCs) remodel or regenerate various tissues through several mechanisms. Here, we identified the hMSC-secreted protein SCRG1 and its receptor BST1 as a positive regulator of self-renewal, migration, and osteogenic differentiation. SCRG1 and BST1 gene expression decreased during osteogenic differentiation of hMSCs. Intriguingly, SCRG1 maintained stem cell marker expression (Oct-4 and CD271/LNGFR) and the potentials of self-renewal, migration, and osteogenic differentiation, even at high passage numbers. Thus, the novel SCRG1/BST1 axis determines the fate of hMSCs by regulating their kinetic and differentiation potentials. Our findings provide a new perspective on methods for ex vivo expansion of hMSCs that maintain native stem cell potentials for bone-forming cell therapy. PMID:24413464

  20. Differentiation

    NSDL National Science Digital Library

    2013-06-21

    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.

  1. The HAND1 Basic Helix-Loop-Helix Transcription Factor Regulates Trophoblast Differentiation via Multiple Mechanisms

    Microsoft Academic Search

    IAN C. SCOTT; LYNN ANSON-CARTWRIGHT; PAUL RILEY; DANNY REDA; JAMES C. CROSS

    2000-01-01

    The basic helix-loop-helix (bHLH) transcription factor genes Hand1 and Mash2 are essential for placental development in mice. Hand1 promotes differentiation of trophoblast giant cells, whereas Mash2 is required for the maintenance of giant cell precursors, and its overexpression prevents giant cell differentiation. We found that Hand1 expression and Mash2 expression overlap in the ectoplacental cone and spongiotrophoblast, layers of the

  2. Schwinger variational principle theory of collisions in the presence of multiple potentials

    E-print Network

    Robicheaux, F; Greene, Chris H

    2015-01-01

    A theoretical method for treating collisions in the presence of multiple potentials is developed by employing the Schwinger variational principle. The current treatment agrees with the local (regularized) frame transformation theory and extends its capabilities. Specifically, the Schwinger variational approach gives results without the divergences that need to be regularized in other methods. Furthermore, it provides a framework to identify the origin of these singularities and possibly improve the local frame transformation. We have used the method to obtain the scattering parameters for different confining potentials symmetric in $x,y$. The method is also used to treat photodetachment processes in the presence of various confining potentials, thereby highlighting effects of the infinitely many closed channels. Two general features predicted are the vanishing of the total photoabsorption probability at {\\it every} channel threshold and the occurrence of resonances below the channel thresholds for negative sc...

  3. Multiple Scattering of Laser Pulses in Snow Over Ice: Modeling the Potential Bias in ICESat Altimetry

    NASA Technical Reports Server (NTRS)

    Davis, A. B.; Varnai, T.; Marshak, A.

    2010-01-01

    The primary goal of NASA's current ICESat and future ICESat2 missions is to map the altitude of the Earth's land ice with high accuracy using laser altimetry technology, and to measure sea ice freeboard. Ice however is a highly transparent optical medium with variable scattering and absorption properties. Moreover, it is often covered by a layer of snow with varying depth and optical properties largely dependent on its age. We describe a modeling framework for estimating the potential altimetry bias caused by multiple scattering in the layered medium. We use both a Monte Carlo technique and an analytical diffusion model valid for optically thick media. Our preliminary numerical results are consistent with estimates of the multiple scattering delay from laboratory measurements using snow harvested in Greenland, namely, a few cm. Planned refinements of the models are described.

  4. Graphene oxide selectively targets cancer stem cells, across multiple tumor types: Implications for non-toxic cancer treatment, via “differentiation-based nano-therapy”

    PubMed Central

    Fiorillo, Marco; Verre, Andrea F.; Iliut, Maria; Peiris-Pagés, Maria; Ozsvari, Bela; Gandara, Ricardo; Cappello, Anna Rita; Sotgia, Federica; Vijayaraghavan, Aravind; Lisanti, Michael P.

    2015-01-01

    Tumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs), are difficult to eradicate with conventional approaches to cancer treatment, such as chemo-therapy and radiation. As a consequence, the survival of residual CSCs is thought to drive the onset of tumor recurrence, distant metastasis, and drug-resistance, which is a significant clinical problem for the effective treatment of cancer. Thus, novel approaches to cancer therapy are needed urgently, to address this clinical need. Towards this end, here we have investigated the therapeutic potential of graphene oxide to target cancer stem cells. Graphene and its derivatives are well-known, relatively inert and potentially non-toxic nano-materials that form stable dispersions in a variety of solvents. Here, we show that graphene oxide (of both big and small flake sizes) can be used to selectively inhibit the proliferative expansion of cancer stem cells, across multiple tumor types. For this purpose, we employed the tumor-sphere assay, which functionally measures the clonal expansion of single cancer stem cells under anchorage-independent conditions. More specifically, we show that graphene oxide effectively inhibits tumor-sphere formation in multiple cell lines, across 6 different cancer types, including breast, ovarian, prostate, lung and pancreatic cancers, as well as glioblastoma (brain). In striking contrast, graphene oxide is non-toxic for “bulk” cancer cells (non-stem) and normal fibroblasts. Mechanistically, we present evidence that GO exerts its striking effects on CSCs by inhibiting several key signal transduction pathways (WNT, Notch and STAT-signaling) and thereby inducing CSC differentiation. Thus, graphene oxide may be an effective non-toxic therapeutic strategy for the eradication of cancer stem cells, via differentiation-based nano-therapy. PMID:25708684

  5. Graphene oxide selectively targets cancer stem cells, across multiple tumor types: implications for non-toxic cancer treatment, via "differentiation-based nano-therapy".

    PubMed

    Fiorillo, Marco; Verre, Andrea F; Iliut, Maria; Peiris-Pagés, Maria; Ozsvari, Bela; Gandara, Ricardo; Cappello, Anna Rita; Sotgia, Federica; Vijayaraghavan, Aravind; Lisanti, Michael P

    2015-02-28

    Tumor-initiating cells (TICs), a.k.a. cancer stem cells (CSCs), are difficult to eradicate with conventional approaches to cancer treatment, such as chemo-therapy and radiation. As a consequence, the survival of residual CSCs is thought to drive the onset of tumor recurrence, distant metastasis, and drug-resistance, which is a significant clinical problem for the effective treatment of cancer. Thus, novel approaches to cancer therapy are needed urgently, to address this clinical need. Towards this end, here we have investigated the therapeutic potential of graphene oxide to target cancer stem cells. Graphene and its derivatives are well-known, relatively inert and potentially non-toxic nano-materials that form stable dispersions in a variety of solvents. Here, we show that graphene oxide (of both big and small flake sizes) can be used to selectively inhibit the proliferative expansion of cancer stem cells, across multiple tumor types. For this purpose, we employed the tumor-sphere assay, which functionally measures the clonal expansion of single cancer stem cells under anchorage-independent conditions. More specifically, we show that graphene oxide effectively inhibits tumor-sphere formation in multiple cell lines, across 6 different cancer types, including breast, ovarian, prostate, lung and pancreatic cancers, as well as glioblastoma (brain). In striking contrast, graphene oxide is non-toxic for "bulk" cancer cells (non-stem) and normal fibroblasts. Mechanistically, we present evidence that GO exerts its striking effects on CSCs by inhibiting several key signal transduction pathways (WNT, Notch and STAT-signaling) and thereby inducing CSC differentiation. Thus, graphene oxide may be an effective non-toxic therapeutic strategy for the eradication of cancer stem cells, via differentiation-based nano-therapy. PMID:25708684

  6. Cigarette smoking hinders human periodontal ligament-derived stem cell proliferation, migration and differentiation potentials.

    PubMed

    Ng, Tsz Kin; Huang, Li; Cao, Di; Yip, Yolanda Wong-Ying; Tsang, Wai Ming; Yam, Gary Hin-Fai; Pang, Chi Pui; Cheung, Herman S

    2015-01-01

    Cigarette smoking contributes to the development of destructive periodontal diseases and delays its healing process. Our previous study demonstrated that nicotine, a major constituent in the cigarette smoke, inhibits the regenerative potentials of human periodontal ligament-derived stem cells (PDLSC) through microRNA (miRNA) regulation. In this study, we hypothesized that the delayed healing in cigarette smokers is caused by the afflicted regenerative potential of smoker PDLSC. We cultured PDLSC from teeth extracted from smokers and non-smokers. In smoker PDLSC, we found significantly reduced proliferation rate and retarded migration capabilities. Moreover, alkaline phosphatase activity, calcium deposition and acidic polysaccharide staining were reduced after BMP2-induced differentiation. In contrast, more lipid deposition was observed in adipogenic-induced smoker PDLSC. Furthermore, two nicotine-related miRNAs, hsa-miR-1305 (22.08 folds, p = 0.040) and hsa-miR-18b (15.56 folds, p = 0.018), were significantly upregulated in smoker PDLSC, suggesting these miRNAs might play an important role in the deteriorative effects on stem cells by cigarette smoke. Results of this study provide further evidences that cigarette smoking affects the regenerative potentials of human adult stem cells. PMID:25591783

  7. Traumatic brain injury alters expression of hippocampal microRNAs: potential regulators of multiple pathophysiological processes.

    PubMed

    Redell, John B; Liu, Yin; Dash, Pramod K

    2009-05-01

    Multiple cellular, molecular, and biochemical changes contribute to outcome after traumatic brain injury (TBI). MicroRNAs (miRNAs) are known to influence many important cellular processes, including proliferation, apoptosis, neurogenesis, angiogenesis, and morphogenesis, all processes that are involved in TBI pathophysiology. However, it has not yet been determined whether miRNA expression is altered after TBI. In the present study, we used a microarray platform to examine changes in the hippocampal expression levels of 444 verified rodent miRNAs at 3 and 24 hr after controlled cortical impact injury. Our analysis found 50 miRNAs exhibited decreased expression levels and 35 miRNAs exhibited increased expression levels in the hippocampus after injury. We extended the microarray findings using quantitative polymerase chain reaction analysis for a subset of the miRNAs with altered expression levels (miR-107, -130a, -223, -292-5p, -433-3p, -451, -541, and -711). Bioinformatic analysis of the predicted targets for this panel of miRNAs revealed an overrepresentation of proteins involved in several biological processes and functions known to be initiated after injury, including signal transduction, transcriptional regulation, proliferation, and differentiation. Our results indicate that multiple protein targets and biological processes involved in TBI pathophysiology may be regulated by miRNAs. PMID:19021292

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

    PubMed Central

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

    1995-01-01

    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

  9. Osteogenic differentiation of amniotic fluid mesenchymal stromal cells and their bone regeneration potential

    PubMed Central

    Pipino, Caterina; Pandolfi, Assunta

    2015-01-01

    In orthopedics, tissue engineering approach using stem cells is a valid line of treatment for patients with bone defects. In this context, mesenchymal stromal cells of various origins have been extensively studied and continue to be a matter of debate. Although mesenchymal stromal cells from bone marrow are already clinically applied, recent evidence suggests that one may use mesenchymal stromal cells from extra-embryonic tissues, such as amniotic fluid, as an innovative and advantageous resource for bone regeneration. The use of cells from amniotic fluid does not raise ethical problems and provides a sufficient number of cells without invasive procedures. Furthermore, they do not develop into teratomas when transplanted, a consequence observed with pluripotent stem cells. In addition, their multipotent differentiation ability, low immunogenicity, and anti-inflammatory properties make them ideal candidates for bone regenerative medicine. We here present an overview of the features of amniotic fluid mesenchymal stromal cells and their potential in the osteogenic differentiation process. We have examined the papers actually available on this regard, with particular interest in the strategies applied to improve in vitro osteogenesis. Importantly, a detailed understanding of the behavior of amniotic fluid mesenchymal stromal cells and their osteogenic ability is desirable considering a feasible application in bone regenerative medicine. PMID:26029340

  10. Differentiating cerebellar and brainstem lesions with ocular vestibular-evoked myogenic potential test.

    PubMed

    Su, Chia-Hung; Young, Yi-Ho

    2011-06-01

    This study applied both ocular vestibular-evoked myogenic potential (oVEMP) and cervical VEMP (cVEMP) tests in patients with cerebellar disorders to determine whether VEMP test can differentiate between cerebellar and brainstem lesions. A total of 12 patients with cerebellar disorder, including extended cerebellar lesion (involving the brainstem) in 8 and localized cerebellar lesion (excluding the brainstem) in 4, were enrolled in this study. All patients underwent caloric, visual suppression, and oVEMP and cVEMP tests via bone-conducted vibration stimuli. The abnormal rates for the caloric, visual suppression, and oVEMP and cVEMP tests were 62, 83, 88 and 75% in patients with extended cerebellar lesion and 0, 25, 0 and 0% in those with localized cerebellar lesion, respectively. The rate of abnormal oVEMP results significantly differed between the two groups, but caloric, visual suppression and cVEMP test results did not differ. In another ten healthy subjects, characteristic parameters of oVEMPs obtained under light and dark conditions did not significantly differ. In conclusion, ocular VEMP test can differentiate between cerebellar and brainstem lesions. Abnormal oVEMPs in patients with cerebellar disorder may indicate adjacent brainstem involvement. PMID:21170655

  11. Differentially expressed plasma microRNAs and the potential regulatory function of Let-7b in chronic thromboembolic pulmonary hypertension.

    PubMed

    Guo, Lijuan; Yang, Yuanhua; Liu, Jie; Wang, Lei; Li, Jifeng; Wang, Ying; Liu, Yan; Gu, Song; Gan, Huili; Cai, Jun; Yuan, Jason X-J; Wang, Jun; Wang, Chen

    2014-01-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) is a progressive disease characterized by misguided thrombolysis and remodeling of pulmonary arteries. MicroRNAs are small non-coding RNAs involved in multiple cell processes and functions. During CTEPH, circulating microRNA profile endued with characteristics of diseased cells could be identified as a biomarker, and might help in recognition of pathogenesis. Thus, in this study, we compared the differentially expressed microRNAs in plasma of CTEPH patients and healthy controls and investigated their potential functions. Microarray was used to identify microRNA expression profile and qRT-PCR for validation. The targets of differentially expressed microRNAs were identified in silico, and the Gene Ontology database and Kyoto Encyclopedia of Genes and Genomes pathway database were used for functional investigation of target gene profile. Targets of let-7b were validated by fluorescence reporter assay. Protein expression of target genes was determined by ELISA or western blotting. Cell migration was evaluated by wound healing assay. The results showed that 1) thirty five microRNAs were differentially expressed in CTEPH patients, among which, a signature of 17 microRNAs, which was shown to be related to the disease pathogenesis by in silico analysis, gave diagnostic efficacy of both sensitivity and specificity >0.9. 2) Let-7b, one of the down-regulated anti-oncogenic microRNAs in the signature, was validated to decrease to about 0.25 fold in CTEPH patients. 3) ET-1 and TGFBR1 were direct targets of let-7b. Altering let-7b level influenced ET-1 and TGFBR1 expression in pulmonary arterial endothelial cells (PAECs) as well as the migration of PAECs and pulmonary arterial smooth muscle cells (PASMCs). These results suggested that CTEPH patients had aberrant microRNA signature which might provide some clue for pathogenesis study and biomarker screening. Reduced let-7b might be involved in the pathogenesis of CTEPH by affecting ET-1 expression and the function of PAECs and PASMCs. PMID:24978044

  12. Upregulation of lncRNA MEG3 Promotes Osteogenic Differentiation of Mesenchymal Stem Cells From Multiple Myeloma Patients By Targeting BMP4 Transcription.

    PubMed

    Zhuang, Wenzhuo; Ge, Xueping; Yang, Sijun; Huang, Moli; Zhuang, Wenyue; Chen, Ping; Zhang, Xiaohui; Fu, Jinxiang; Qu, Jing; Li, Bingzong

    2015-06-01

    Multiple myeloma (MM) is characterized by the impaired osteogenic differentiation of mesenchymal stromal cells (MSCs). However, the underlying molecular mechanisms are still poorly understood. Long noncoding RNAs (lncRNAs) are emerging as important regulatory molecules in tumor-suppressor and oncogenic pathways. Here we showed that MSCs from MM expressed less lncRNA MEG3 relative to those from normal donors during osteogenic differentiation. To evaluate the effect of MEG3 on osteogenesis, bone marrow MSCs with enhanced or reduced MEG3 were prepared. We observed that MEG3 knockdown significantly reduced the expression of key osteogenic markers, including Runt-related transcription factor 2, osterix, and osteocalcin, while overexpression of MEG3 enhanced their expression. Additionally, MEG3 knockdown decreased BMP4 transcription. Here we showed that MEG3 was critical for SOX2 transcriptional repression of the BMP4. MEG3, which is located near the BMP4 gene, could dissociate the transcription factor SOX2 from the BMP4 promoter. A stable complex containing the MEG3, SOX2, and the SOX2 consensus site of BMP4 suggested that MEG3 activated transcriptional activity by directly influencing SOX2 activity. By using assays such as luciferase, chromatin immunoprecipitation, and RNA immunoprecipitation, we showed that MEG3 had a critical function in a mechanism of promoter-specific transcriptional activation. These results suggested that MEG3 played an essential role in osteogenic differentiation in bone marrow MSCs, partly by activating BMP4 transcription. Our data provided novel evidence for the biological and clinical significance of lncRNA MEG3 expression as a potential biomarker for identifying patients with MM and as a potential therapeutic target in MM. Stem Cells 2015;33:1985-1997. PMID:25753650

  13. EFFECT OF THIDIAZURON ON IN VITRO PROLIFERATION CAPACITIES OF SOME BANANA (Musa spp.) CULTIVARS WITH WEAK MULTIPLICATION POTENTIAL

    Microsoft Academic Search

    Emmanuel YOUMBI; Blaise ELLA; Kodjo TOMEKPE

    The multiplication and the distribution of plant material is one of the objectives of plant tissue culture laboratory of African Research Centre on Bananas and Plantains (ARCBAP). Some banana (Musa spp.) cultivars including Topala, Fougamou, Gros-Michel shows low proliferation when cultured in vitro. Other cultivars like Dwarf-Kalapua, Pelipita and Kalapua 2 take long time (two months) to be differentiated in

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

    SciTech Connect

    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

    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.

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

    ERIC Educational Resources Information Center

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

    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…

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

    ERIC Educational Resources Information Center

    Rothbart, Mary K.

    2004-01-01

    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…

  17. A Role of Canonical Transient Receptor Potential 5 Channel in Neuronal Differentiation from A2B5 Neural Progenitor Cells

    Microsoft Academic Search

    Hye Young Shin; Yun Hwa Hong; Sung Soo Jang; Hong Gu Chae; Seung Leal Paek; Hyo Eun Moon; Dong Gyu Kim; Jun Kim; Sun Ha Paek; Sang Jeong Kim; Tailoi Chan-Ling

    2010-01-01

    Store-operated Ca2+ entry (SOCE) channels are the main pathway of Ca2+ entry in non-excitable cells such as neural progenitor cells (NPCs). However, the role of SOCE channels has not been defined in the neuronal differentiation from NPCs. Here, we show that canonical transient receptor potential channel (TRPC) as SOCE channel influences the induction of the neuronal differentiation of A2B5+ NPCs

  18. Multiple-scale analysis of discrete nonlinear partial difference equations: the reduction of the lattice potential KdV

    Microsoft Academic Search

    D. Levi

    2005-01-01

    We consider multiple lattices and functions defined on them. We introduce slow varying conditions for functions defined on the lattice and express the variation of a function in terms of an asymptotic expansion with respect to the slow varying lattices. We use these results to perform multiple-scale reduction of the lattice potential Korteweg-de Vries equation.

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

    PubMed Central

    Messerli, Marianne; Wagner, Anna; Sager, Ruth; Mueller, Martin; Baumann, Marc; Schoeberlein, Andreina

    2013-01-01

    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

  20. LSD-potentiated apomorphine hypermotility: a model for differentiating antipsychotic drugs.

    PubMed

    Morgenstern, R; Fink, H; Oelssner, W

    1983-01-01

    The model of LSD-potentiated apomorphine hypermotility (LPAH) in rats in comparison to apomorphine-induced hypermotility (AH) was used to investigate typical and atypical neuroleptics by analyzing complete dose response curves. Haloperidol (0.06 mg/kg) induced a parallel shift to the right of both the AH and LPAH dose response curves indicating dopaminolytic properties without any serotonolytic effect. Chlorpromazine (0.5 mg/kg) caused a mixed inhibitory effect on the LPAH, whereas the AH was not affected, probably due to the variety of actions at different transmission systems. Clozapine (0.125 mg/kg) antagonized the LSD effect indicating serotonolytic properties, whereas an additive influence on the AH might be caused by its cholinolytic properties. Sulpiride (10 mg/kg) potentiated both the AH and the LPAH, probably due to presynaptic dopaminergic mechanisms. Two conclusions can be drawn: (1) The results agree with and support the idea of a serotonergic modulation of the (predominant) mesolimbic dopaminergic system in the induction of locomotor effects. (2) The model of LPAH is useful to clearly differentiate typical from atypical neuroleptics, and to obtain information whether there is a primary involvement of dopaminergic or serotonergic mechanisms. PMID:6681904

  1. Phasor fluorescence lifetime microscopy of free and protein-bound NADH reveals neural stem cell differentiation potential.

    PubMed

    Stringari, Chiara; Nourse, Jamison L; Flanagan, Lisa A; Gratton, Enrico

    2012-01-01

    In the stem cell field there is a lack of non invasive and fast methods to identify stem cell's metabolic state, differentiation state and cell-lineage commitment. Here we describe a label-free method that uses NADH as an intrinsic biomarker and the Phasor approach to Fluorescence Lifetime microscopy to measure the metabolic fingerprint of cells. We show that different metabolic states are related to different cell differentiation stages and to stem cell bias to neuronal and glial fate, prior the expression of lineage markers. Our data demonstrate that the NADH FLIM signature distinguishes non-invasively neurons from undifferentiated neural progenitor and stem cells (NPSCs) at two different developmental stages (E12 and E16). NPSCs follow a metabolic trajectory from a glycolytic phenotype to an oxidative phosphorylation phenotype through different stages of differentiation. NSPCs are characterized by high free/bound NADH ratio, while differentiated neurons are characterized by low free/bound NADH ratio. We demonstrate that the metabolic signature of NPSCs correlates with their differentiation potential, showing that neuronal progenitors and glial progenitors have a different free/bound NADH ratio. Reducing conditions in NPSCs correlates with their neurogenic potential, while oxidative conditions correlate with glial potential. For the first time we show that FLIM NADH metabolic fingerprint provides a novel, and quantitative measure of stem cell potential and a label-free and non-invasive means to identify neuron- or glial- biased progenitors. PMID:23144844

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

    PubMed Central

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

    2014-01-01

    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. PMID:25755907

  3. DIFFERENTIAL INFORMATION CONTENT IN STAGGERED MULTIPLE SHELL HARDI MEASURED BY THE TENSOR DISTRIBUTION FUNCTION

    E-print Network

    Thompson, Paul

    DISTRIBUTION FUNCTION Liang Zhan1 , Alex D. Leow2, 3 , Iman Aganj4 , Christophe Lenglet5, 4 , Guillermo Sapiro4/mm2 ). In experiments with the tensor distribution function (TDF), the b-value affected the intrinsic diffusion imaging (HYDI) samples the radial and angular structure of local diffusion on multiple spherical

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

    ERIC Educational Resources Information Center

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

    2013-01-01

    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…

  5. Meaning Change, Multiple Routes, and the Role of Differentiation in Conceptual Change: Alternatives to Resubsumption?

    ERIC Educational Resources Information Center

    Ohlsson, Stellan

    2009-01-01

    The three commentaries on the resubsumption theory highlight three key ideas: that the term "conceptual change", as commonly used, is ambiguous between "change in the meaning of a concept" and "change in what someone believes"; that there are multiple routes to successful learning of conceptual subject matters; and that the noticing of a…

  6. Differential sensitivity of three marine invertebrates to copper assessed using multiple biomarkers

    Microsoft Academic Search

    R. J. Brown; T. S. Galloway; D. Lowe; M. A. Browne; A. Dissanayake; M. B. Jones; M. H. Depledge

    2004-01-01

    Understanding how biomarkers relate to each other on exposure to particular contaminants in different species is key to their widespread application in environmental management. However, few studies have systematically used multiple biomarkers in more than a single species to determine the variability of sublethal effects of a particular contaminant. In this study, three marine invertebrates, the shore crab Carcinus maenas,

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

    ERIC Educational Resources Information Center

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

    2005-01-01

    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…

  8. Stretchable energy-harvesting tactile electronic skin capable of differentiating multiple mechanical stimuli modes.

    PubMed

    Park, Steve; Kim, Hyunjin; Vosgueritchian, Michael; Cheon, Sangmo; Kim, Hyeok; Koo, Ja Hoon; Kim, Taeho Roy; Lee, Sanghyo; Schwartz, Gregory; Chang, Hyuk; Bao, Zhenan

    2014-11-19

    The first stretchable energy-harvesting electronic-skin device capable of differentiating and generating energy from various mechanical stimuli, such as normal pressure, lateral strain, bending, and vibration, is presented. A pressure sensitivity of 0.7 kPa(-1) is achieved in the pressure region <1 kPa with power generation of tens of ?W cm(-2) from a gentle finger touch. PMID:25256696

  9. PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells

    Microsoft Academic Search

    Keith R. Shockley; Oxana P. Lazarenko; Piotr J. Czernik; Clifford J. Rosen; Gary A. Churchill; Czernik B Lecka

    2009-01-01

    Rosiglitazone (Rosi), a member of the thiazolidinedione class of drugs used to treat type 2 diabetes, activates the adipocyte-specific transcription factor peroxisome proliferator-activated receptor gamma (PPARgamma). This activation causes bone loss in animals and humans, at least in part due to suppression of osteoblast differentiation from marrow mesenchymal stem cells (MSC). In order to identify mechanisms by which PPARgamma2 suppresses

  10. Unwrapping differential x-ray phase-contrast images through phase estimation from multiple energy data.

    PubMed

    Epple, F M; Potdevin, G; Thibault, P; Ehn, S; Herzen, J; Hipp, A; Beckmann, F; Pfeiffer, F

    2013-12-01

    We present a spectral phase unwrapping approach for grating-based differential phase-contrast data where the unwrapped interferometer phase shift is estimated from energy discriminated measurements using maximum likelihood principles. We demonstrate the method on tomographic data sets of a test specimen taken at different x-ray energies using synchrotron radiation. The proposed unwrapping technique was demonstrated to successfully correct the data set for phase wrapping. PMID:24514461

  11. The bHLH Gene Hes1 Regulates Differentiation of Multiple Cell Types

    Microsoft Academic Search

    Ryoichiro Kageyama; Toshiyuki Ohtsuka; Koichi Tomita

    2000-01-01

    For embryos that have small pancreas and lack brain, eyes and thymus, the defects are caused by mutation of a single gene,\\u000a Hes1. Hes1 encodes a basic helix-loop-helix (bHLH) transcriptional repressor and functionally antagonizes positive bHLH genes such as\\u000a the neuronal determination gene, Mash1. Mis-expression of Hes1 inhibits cell differentiation and keeps cells at the precursor stage or proliferative stage.

  12. Can Vestibular-Evoked Myogenic Potentials Help Differentiate Méničre Disease from Vestibular Migraine?

    PubMed Central

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

    2013-01-01

    Objectives To characterize both cervical and ocular vestibular-evoked myogenic potential (cVEMP, oVEMP) responses to air-conducted sound (ACS) and midline taps in Méničre 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

  13. Multiplication

    NSDL National Science Digital Library

    Ms. Williams

    2011-04-06

    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 ...

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

    PubMed

    Bleiker, K P; Six, D L

    2007-12-01

    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

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

    E-print Network

    Wilson, Ryan Justin

    2004-09-30

    .................................................................................. 73 Inverse scattering multiple attenuation (ISMA)......................................... 78 Attenuating free-surface multiples and receiver ghosts while... preserving primaries................................................... 81 Attenuating free-surface multiples and their receiver ghosts while preserving primaries...

  16. Differential effects of stress on a murie model of multiple sclerosis.

    E-print Network

    Heibel, Jessica

    2011-08-08

    -pituitary-adrenocortical I&D Inflammation and demyelination MBP Myelin basic protein MHC Major histocompatibility complex MOG Myelin oligodendrocyte glycoprotein MRI Magnetic resonance imaging MS Multiple sclerosis NK cell Natural killer cell NRS No restraint stress... reaction. Antibodies against target antigens, such as myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG), are able to infiltrate the CNS due to the T-cells disruption of the _______________ This thesis follows the style of Brain...

  17. Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro

    Microsoft Academic Search

    Oliver Neuhaus; Heinz Wiendl; Bernd C. Kieseier; Juan J. Archelos; Bernhard Hemmer; Olaf Stüve; Hans-Peter Hartung

    2005-01-01

    Mitoxantrone is an anti-neoplastic anthracenedione derivative that, based on its immunosuppressive properties, is approved for the treatment of severe forms of relapsing–remitting or secondary progressive multiple sclerosis (MS). Whether the beneficial clinical effects of mitoxantrone in MS are due to a broad immunosuppression, or whether there is a specific mechanism of action remains unknown.Peripheral blood mononuclear cells (PBMCs) from untreated

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

    PubMed Central

    Kim, J HK; Pullan, A J; Cheng, L K

    2012-01-01

    One approach, 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 was 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. PMID:22842812

  19. Multiple regulation of S14 gene expression during brown fat differentiation.

    PubMed

    Perez-Castillo, A; Hernandez, A; Pipaon, C; Santos, A; Obregon, M J

    1993-08-01

    S14 is a gene known to be under thyroid hormone control. Its mRNA concentration is very high in lipogenic tissues, and although the precise function of the protein is still unknown, indirect data suggest its implication in triglyceride synthesis. S14 gene expression is up-regulated by thyroid hormone in liver, white adipose tissue, and lactating mammary gland. However, in brown fat, the level of this sequence is increased 3-fold in the hypothyroid animal. We have used primary cultures of brown preadipocytes differentiated to fully mature brown adipocytes to investigate the influence of cellular differentiation and hormonal stimulation on S14 gene expression. Steady state levels of S14 mRNA rose from nondetectable levels in preadipocytes to reach a maximum in fully mature adipocytes. Treatment of brown adipocytes cultures with T3 did induce S14 gene expression. This induction reflects in part a posttranscriptional stabilization of the messenger by T3. Insulin, insulin-like growth factor-I, and inositol phosphate-glycan also increase the level of S14 mRNA. Norepinephrine (NE) plays a major role in the regulation of S14 gene, and 24 h after its addition, NE elicited a 20-fold decrease in mRNA S14 concentrations. An elevated intracellular concentration of cAMP is a strong negative effector of S14 gene expression, and neither NE nor cAMP action is totally overcome by T3. As happens in vivo, glucose is a potent stimulator of S14 mRNA; however, there is a lag time of several hours before its effects can be detected. The increase in S14 gene expression with the maturation stage of the cell suggests an important role for S14 in adipocyte differentiation. PMID:8393767

  20. Decision-feedback multiple differential detection for space-time coded OFDM systems

    E-print Network

    Liu, Yan

    2001-01-01

    line frequency selective fading channel model, Rayleigh fading process with different normalized Dopplers . Differential encoder and decoder BER of conventional difhrential detection of BPSK in various channel conditions 10 Block diagram... of the transmission model 12 Structure ol' the DF-DD receiver BER of DF-DD ODPSK in Rayleigh flat fading channel for nor- malized Doppler=0. 003 BER of DF-DD QDPSK in Rayicigh flat fading channel for nor- malized Doppler=0. 0075 . 10 BL'R of DF-DD QDPSK...

  1. Differential Enantioselective Transformation of Atropisomeric Polychlorinated Biphenyls by Multiple Bacterial Strains with Different Inducing Compounds

    PubMed Central

    Singer, Andrew C.; Wong, Charles S.; Crowley, David E.

    2002-01-01

    Five polychlorinated biphenyl (PCB)-degrading bacteria were tested for the ability to differentiate between the enantiomers of four atropisomeric PCB congeners (2,2?,3,6-tetra-CB; 2,2?,3,3?,6-penta-CB; 2,2?,3,4?,6-penta-CB; and 2,2?,3,5?,6-penta-CB) after growth in the presence of tryptone-soytone, biphenyl, carvone, or cymene. Enantioselectivity was shown to vary with respect to strain, congener, and cosubstrate. PMID:12406776

  2. UAV based tree height estimation in apple orchards: potential of multiple approaches

    NASA Astrophysics Data System (ADS)

    Mejia-Aguilar, Abraham; Tomelleri, Enrico; Vilardi, Andrea; Zebisch, Marc

    2015-04-01

    Canopy height, as part of vegetation structure, is ecologically important for ecological studies on biomass, matter flows or meteorology. Measuring the growth of canopy can be undertaken by the use multiple remote sensing techniques. In this study, we firstly use data generated from an Unmanned Aerial Vehicles (UAV) with a simultaneous consumer-grade RGB and modified IR cameras, configured in nadir and multi-angle views to generate 3D models for Digital Surface Model (DSM) and Digital Terrain Models (DTM) in order to estimate tree height in apple orchards in South Tyrol, Italy. We evaluate the use of Ground Control Points (GCP) to minimize the error in scale and orientation. Then, we validate and compare the results of our primary data collection with data generated by geolocated field measurements over several selected tree species. Additionally, we compare DSM and DTM obtained from a recent 1-meter resolution LIDAR campaign (Light Detection and Ranging). The main purpose of this study is to contrast multiple estimation approaches and evaluate their utility for the estimation of canopy height, highlighting the use of UAV systems as a fast, reliable and non-expensive technique especially for small scale applications. The study is conducted in a homogenous tree canopy consisting of apple orchards located in Caldaro -South Tyrol, Italy. We end with proposing a potential low-cost and inexpensive application combining models for DSM from the UAV with DTM obtained from LIDAR for applications that should be updated frequently.

  3. [Ipsilateral masking of auditory evoked potentials: a method of studying multiple sclerosis].

    PubMed

    Antonelli, A; Collette, J L; Bellotto, R; Felisati, G; Pavani, M; Cesaro, P; Degos, J D; Peynegre, R

    1984-01-01

    20 normal subjects and 39 patients with multiple sclerosis were the control and the test groups. Auditory brainstem potentials to 60 dB nHL, 11/s clicks, were recorded under ipsilateral broad-band noise masking at S/N ratio of + 60 dB (unmasked condition), + 20 dB, + 10 dB and 0 dB. In the control group the ABP were absent only in 1 subject at S/N = 0 dB. In the group of 16/39 patients with definite multiple sclerosis, 11 had no ABP at S/N = 0 dB, 6 at S/N = + 10 dB and 5 at S/N = + 20 dB. The ABP waveform per se, in the same subjects, was abnormal in 7 and doubtful in 5. These results are discussed in terms of sensitivity, specificity and efficiency of the test to be applied. The best predictive value is achieved by combining a strict morphological criterion with the results of the ipsilateral masking. Moreover, the ipsilateral masking test positive findings are equally distributed in the group of patients with and without signs of neurological involvement of the brainstem. PMID:6534258

  4. Cognition in relapsing-remitting multiple sclerosis: a multichannel event-related potential (P300) study.

    PubMed

    Triantafyllou, N I; Voumvourakis, K; Zalonis, I; Sfagos, K; Mantouvalos, V; Malliara, S; Papageorgiou, C

    1992-01-01

    Auditory event-related potentials (AERP) were elicited in 47 patients with relapsing-remitting (RR) multiple sclerosis (MS) and 24 age-matched controls. MS patients had significantly prolonged N2 and P3 latencies as well as low P3 amplitude compared with controls. Seven of them exceeded 3 standard deviations from the control mean values. The observed N2 and P3 alterations are associated with the patients' disability status as it is defined by the Kurtzke expanded disability status scale (EDSS), but are not related to the duration of the disease. A possible cognitive decline as reflected in the observed AERP components alterations in MS patients is subsequently discussed. PMID:1546528

  5. Multiple chemical sensitivity (MCS)--differential diagnosis in clinical neurotoxicology: a German perspective.

    PubMed

    Altenkirch, H

    2000-08-01

    The multiple chemical sensitivity syndrome (MCS) is a new cluster of environmental symptoms which have been described and commented on for more than 15 years now in the USA. In the meantime it has also been observed in European countries. The main features of this syndrome are: multiple symptoms in multiple organ systems, precipitated by a variety of chemical substances with relapses and exacerbation under certain conditions when exposed to very low levels which do not affect the population at large. There are no lab markers or specific investigative findings. In our view, MCS is not a separate clinical syndrome but a collective term. A very small part of the patients in question may actually exhibit a somatic or psychosomatic response to low levels of a variety of chemicals in the environment. For another part, even if the MCS symptoms are induced by chemical substances in the environment, the basic hypersensitivity is a psychological stress reaction. In the third and largest group, the patients have been misdiagnosed, i.e. a somatic or psychiatric disease has been overlooked. There is a fourth group of patients in whom there is no evidence of any exposure at all but instead a belief system installed by certain physicians, the media and other groups in society. This paper tries to describe the neurological and neurotoxic aspects of MCS problems and to illustrate it with examples of an alleged outbreak of chronic neurotoxic disease caused by pyrethroids in Germany. Research strategy should establish clearly determined diagnostic criteria, agreement on the use of specific questionnaires as well as clinical and technical diagnostic procedures, prospective clinical studies of MCS patients and comparative groups as well as experimental approaches. PMID:11022866

  6. A multiple instrument study to differentiate primary versus secondary gravity-wave generation in the mesosphere

    NASA Astrophysics Data System (ADS)

    Espy, Patrick; Demissie, Teferi; Hatlen, Morten; Hibbins, Robert; de Witt, Rosmarie; Swenson, Gary; Vargas, Fabio

    2013-04-01

    A sensitive, all-sky camera has been used to image mesospheric airglow emissions at Trondheim, Norway (63.4N, 10.3W) during the winter of 2012-2013. Images of the hydroxyl and sodium airglows have been used to infer the presence of gravity waves passing through these layers located between 87 and 93km. Simultaneously, a new, 30kW, momentum-flux meteor-radar system observed the horizontal wind field. These data, along with meteorological balloon soundings, have been combined with a code to trace gravity-waves from their source regions in order to differentiate primary from secondary wave generation mechanisms. We will present the image analysis and the effects of the background wind field on the gravity-wave transmission in order to ascertain the source region of the waves observed near the mesopause.

  7. A Simple Differential Equation Associating Multiple Types of Probability Distributions in Characterization of Noninear Processes in Geosciences

    NASA Astrophysics Data System (ADS)

    Cheng, Q.

    2014-12-01

    Probability distributions or probability density functions are commonly used in geosciences for purposes ranging from characterization, estimation, prediction and assessment. Each type of probability distribution is found suitable for describing certain types of phenomena and processes, for example, the normal distribution is used, ensured by the classical Central Limit Theorem, to characterizing physical quantities summed many independent processes such as measurement errors, gamma distribution is frequently used to model waiting times, Pareto distribution to extreme events, power-law distribution to frequency-size distribution of earthquakes and inverse gamma distribution for self-organized criticality description of landslides. Understanding the associations of these types of probability distributions is essential not only for determining usage of these distributions but also for interpretation of the results. In this paper we demonstrate that a simple non-linear first order differential equation can be used to describe the decay function of probability density around the mean values. Assume the decay rate of probability density function is negatively proportional to the density itself or a power of the density, with a functional coefficient dependent on the value of the random variable. Applying Taylor series expansion to the coefficient function, the differential equation can be approximated by multiple simple dynamic systems, each with explicit solutions. These functions can be utilized either as separate and combined solutions to generate various commonly used probability distributions including but not limited to Gaussian, power-law, gamma, inverse gamma, Pareto, Weibull, Rayleigh, and Maxwell-Boltzmann distributions. The association of these types of distributions provides insight into multiple types of probability distributions commonly used in characterization of extreme events in nonlinear processes in geosciences.

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

    PubMed Central

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

    2014-01-01

    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

  9. Verification of genes differentially expressed in neuroblastoma tumours: a study of potential tumour suppressor genes

    PubMed Central

    Thorell, Kaisa; Bergman, Annika; Carén, Helena; Nilsson, Staffan; Kogner, Per; Martinsson, Tommy; Abel, Frida

    2009-01-01

    Background One of the most striking features of the childhood malignancy neuroblastoma (NB) is its clinical heterogeneity. Although there is a great need for better clinical and biological markers to distinguish between tumours with different severity and to improve treatment, no clear-cut prognostic factors have been found. Also, no major NB tumour suppressor genes have been identified. Methods In this study we performed expression analysis by quantitative real-time PCR (QPCR) on primary NB tumours divided into two groups, of favourable and unfavourable outcome respectively. Candidate genes were selected on basis of lower expression in unfavourable tumour types compared to favourables in our microarray expression analysis. Selected genes were studied in two steps: (1) using TaqMan Low Density Arrays (TLDA) targeting 89 genes on a set of 12 NB tumour samples, and (2) 12 genes were selected from the TLDA analysis for verification using individual TaqMan assays in a new set of 13 NB tumour samples. Results By TLDA analysis, 81 out of 87 genes were found to be significantly differentially expressed between groups, of which 14 have previously been reported as having an altered gene expression in NB. In the second verification round, seven out of 12 transcripts showed significantly lower expression in unfavourable NB tumours, ATBF1, CACNA2D3, CNTNAP2, FUSIP1, GNB1, SLC35E2, and TFAP2B. The gene that showed the highest fold change in the TLDA analysis, POU4F2, was investigated for epigenetic changes (CpG methylation) and mutations in order to explore the cause of the differential expression. Moreover, the fragile site gene CNTNAP2 that showed the largest fold change in verification group 2 was investigated for structural aberrations by copy number analysis. However, the analyses of POU4F2 and CNTNAP2 showed no genetic alterations that could explain a lower expression in unfavourable NB tumours. Conclusion Through two steps of verification, seven transcripts were found to significantly discriminate between favourable and unfavourable NB tumours. Four of the transcripts, CACNA2D3, GNB1, SLC35E2, and TFAP2B, have been observed in previous microarray studies, and are in this study independently verified. Our results suggest these transcripts to be markers of malignancy, which could have a potential usefulness in the clinic. PMID:19686582

  10. 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

    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

    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.

  11. Disease Exacerbation of Multiple Sclerosis is Characterized by Loss of Terminally Differentiated Autoregulatory CD8+ T cells

    PubMed Central

    Cunnusamy, Khrishen; Baughman, Ethan J.; Franco, Jorge; Ortega, Sterling B.; Sinha, Sushmita; Chaudhary, Parul; Greenberg, Benjamin M.; Frohman, Elliot M.; Karandikar, Nitin J.

    2014-01-01

    Multiple sclerosis (MS) is an inflammatory, demyelinating disease of the central nervous system (CNS). Although its etiology remains unknown, pathogenic T cells are thought to underlie MS immune pathology. We recently showed that MS patients harbor CNS-specific CD8+ Tregs that are deficient during disease relapse. We now demonstrate that CNS-specific CD8+ Tregs were cytolytic and could eliminate pathogenic CD4+ T cells. These CD8+ Tregs were present primarily in terminally differentiated (CD27?, CD45RO?) subset and their suppression was IFN?, perforin and granzyme B-dependent. Interestingly, MS patients with acute relapse displayed a significant loss in terminally differentiated CD8+ T cells, with a concurrent loss in expression of perforin and granzyme B. Pre-treatment of exacerbation-derived CD8+ T cells with IL-12 significantly restored suppressive capability of these cells through upregulation of granzyme B. Our studies uncover immune-suppressive mechanisms of CNS-specific CD8+ Tregs, and may contribute to design of novel immune therapies for MS. PMID:24657764

  12. Transcripts of unknown function in multiple-signaling pathways involved in human stem cell differentiation

    Microsoft Academic Search

    Kunio Kikuchi; Makiha Fukuda; Tomoya Ito; Mitsuko Inoue; Takahide Yokoi; Suenori Chiku; Toutai Mitsuyama; Kiyoshi Asai; Tetsuro Hirose; Yasunori Aizawa

    2009-01-01

    Mammalian transcriptome analysis has uncovered tens of thousands of novel transcripts of unknown function (TUFs). Classical and recent examples suggest that the majority of TUFs may underlie vital intracellular functions as non-coding RNAs because of their low coding potentials. However, only a portion of TUFs have been studied to date, and the functional significance of TUFs remains mostly uncharacterized. To

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

    PubMed

    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

    2015-05-01

    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. PMID:25388955

  14. Neurotrophin-3 gene-modified Schwann cells promote TrkC gene-modified mesenchymal stem cells to differentiate into neuron-like cells in poly(lactic-acid-co-glycolic acid) multiple-channel conduit.

    PubMed

    Zhang, Yan-qing; He, Liu-min; Xing, Bin; Zeng, Xiang; Zeng, Chen-guang; Zhang, Wei; Quan, Da-ping; Zeng, Yuan-shan

    2012-01-01

    Rapid progress in the field of nerve tissue engineering has opened up the way for new therapeutic strategies for spinal cord injury (SCI). Bone marrow-derived mesenchymal stem cells (MSCs) could be differentiated into neural lineages, which can be used as a potential cell source for nerve repair. Schwann cells (SCs) have been reported to support structural and functional recovery of SCI. In this study, we co-cultured neurotrophin-3 (NT-3) gene-modified SCs and NT-3 receptor tyrosine protein kinase C (TrkC) gene-modified MSCs in a three-dimensional porous poly(lactic-acid-co-glycolic acid) (PLGA) conduit with multiple channels in vitro for 14 days. Our results showed that more than 50% of the grafted MSCs were MAP2- and ?-III-tubulin-positive cells, and the MSCs expressed a high level of ?-III-tubulin detected by Western blotting, indicating a high rate of neuronal differentiation. Furthermore, immunostaining of PSD95 revealed the formation of a synapse-like structure, which was confirmed under electron microscopy. In conclusion, co-culture of NT-3 gene-modified SCs and TrkC gene-modified MSCs in the PLGA multiple-channeled conduit can promote MSCs' differentiation into neuron-like cells with synaptogenesis potential. Our study provides a biological basis for future application of this artificial MSCs/SCs/PLGA complex in the SCI treatment. PMID:21828999

  15. Embryonic stem cell-specific microRNAs contribute to pluripotency by inhibiting regulators of multiple differentiation pathways

    PubMed Central

    Gruber, Andreas J.; Grandy, William A.; Balwierz, Piotr J.; Dimitrova, Yoana A.; Pachkov, Mikhail; Ciaudo, Constance; van Nimwegen, Erik; Zavolan, Mihaela

    2014-01-01

    The findings that microRNAs (miRNAs) are essential for early development in many species and that embryonic miRNAs can reprogram somatic cells into induced pluripotent stem cells suggest that these miRNAs act directly on transcriptional and chromatin regulators of pluripotency. To elucidate the transcription regulatory networks immediately downstream of embryonic miRNAs, we extended the motif activity response analysis approach that infers the regulatory impact of both transcription factors (TFs) and miRNAs from genome-wide expression states. Applying this approach to multiple experimental data sets generated from mouse embryonic stem cells (ESCs) that did or did not express miRNAs of the ESC-specific miR-290-295 cluster, we identified multiple TFs that are direct miRNA targets, some of which are known to be active during cell differentiation. Our results provide new insights into the transcription regulatory network downstream of ESC-specific miRNAs, indicating that these miRNAs act on cell cycle and chromatin regulators at several levels and downregulate TFs that are involved in the innate immune response. PMID:25030899

  16. Cervical and ocular vestibular evoked myogenic potentials in multiple sclerosis participants

    PubMed Central

    Parsa, Maryam Sadat; Mohammadkhani, Ghassem; Hajabolhassani, Fahimeh; Jalaee, Shohreh; Zakeri, Hassanali

    2015-01-01

    Background: Multiple sclerosis (MS) is a chronic neurological disease that affects brain and spinal cord. The infratentorial region contains the cerebellum and brainstem. Vestibular evoked myogenic potentials (VEMPs) are short-latency myogenic responses. Cervical vestibular evoked myogenic potential (cVEMP) is a manifestation of vestibulocolic reflex and ocular vestibular evoked myogenic potential (oVEMP) contributes to the linear vestibular–ocular reflex. The aim of this study was to evaluate cVEMP and oVEMP in MS patients with and without infratentorial plaques and compare the findings with normal controls. Methods: In this cross-sectional study, latency and amplitude of cVEMP and oVEMP were recorded in 15 healthy females with mean age of 31.13±9.27 years, 17 female MS patients with infratentorial plaque(s) and mean age of 29.88±8.93 years, and 17 female MS patients without infratentorial plaque(s) and mean age of 30.58±8.02 years. All patients underwent a complete clinical neurological evaluation and brain MRI scanning. Simple random sampling method was used in this study and data were analyzed using one way ANOVA through SPSS v22. Results: The latency of N1-P1 and P13 in MS participants with and without infratentorial plaques were significantly prolonged compared to normal controls (p<0.001). Additionally latency of P13- N23-N1 and P1 in MS patients with infratentorial plaques were significantly prolonged compared to patients without infratentorial plaques subjects (p<0.001). Conclusion: Abnormality of both cVEMP and oVEMP in MS patient with infratentorial plaque are more than that of MS patient without infratentorial plaque. Recording both ocular and cervical VEMPs are appropriate electrophysiologic methods assessing the function of both ascending and descending central vestibular pathways. PMID:26034721

  17. A label-free high throughput resistive-pulse sensor for simultaneous differentiation and measurement of multiple particle-laden analytes

    Microsoft Academic Search

    Ashish V. Jagtiani; Rupesh Sawant; Jiang Zhe

    2006-01-01

    We describe an all-electronic, label-free, resistive-pulse sensor that utilizes multiple microchannels for parallel detection, counting and differentiation of multiple biological particles simultaneously. Four particle solutions, including 20 µm and 40 µm polymethacrylate particles, Juniper Scopulorum (Rocky Mountain Juniper) pollen and Populus deltidoes (Eastern Cottonwood) pollen, were loaded to the four peripheral reservoirs, respectively, and were driven to the central reservoir

  18. Differential activation of multiple current sources of foveal VEPs as a function of spatial frequency

    Microsoft Academic Search

    Alice Mado Proverbio; Alberto Zani; Carmela Avella

    1996-01-01

    Summary The purpose of the present study was to map sensory-evoked potentials to foveally presented square-wave gratings of different spatial frequencies with a high density electrode montage. Scalp isocontour voltage and scalp current density (SCD) maps were computed to assess differences in scalp topography of the sensory-evoked responses as a function of spatial frequency. Topographic analysis showed a segregation of

  19. Multiple roles for Plasmodium berghei phosphoinositide-specific phospholipase C in regulating gametocyte activation and differentiation

    PubMed Central

    Raabe, Andreas C; Wengelnik, Kai; Billker, Oliver; Vial, Henri J

    2011-01-01

    Critical events in the life cycle of malaria parasites are controlled by calcium-dependent signalling cascades, yet the molecular mechanisms of calcium release remain poorly understood. The synchronized development of Plasmodium berghei gametocytes relies on rapid calcium release from internal stores within 10 s of gametocytes being exposed to mosquito-derived xanthurenic acid (XA). Here we addressed the function of phosphoinositide-specific phospholipase C (PI-PLC) for regulating gametocyte activation. XA triggered the hydrolysis of PIP2 and the production of the secondary messenger IP3 in gametocytes. Both processes were selectively blocked by a PI-PLC inhibitor, which also reduced the early Ca2+ signal. However, microgametocyte differentiation into microgametes was blocked even when the inhibitor was added up to 5 min after activation, suggesting a requirement for PI-PLC beyond the early mobilization of calcium. In contrast, inhibitors of calcium release through ryanodine receptor channels were active only during the first minute of gametocyte activation. Biochemical determination of PI-PLC activity was confirmed using transgenic parasites expressing a fluorescent PIP2/IP3 probe that translocates from the parasite plasmalemma to the cytosol upon cell activation. Our study revealed a complex interdependency of Ca2+ and PI-PLC activity, with PI-PLC being essential throughout gamete formation, possibly explaining the irreversibility of this process. PMID:21518218

  20. Differential Development of Glucose Intolerance and Pancreatic Islet Adaptation in Multiple Diet Induced Obesity Models

    PubMed Central

    Omar, Bilal; Pacini, Giovanni; Ahrén, Bo

    2012-01-01

    Background: The C57BL/6 mouse fed a high fat diet is a common and valuable model in experimental studies of obesity and type 2 diabetes (T2D). Different high fat diets are used and in order to determine which diet produces a model most accurately resembling human T2D, they need to be compared head-to-head. Methods: Four different diets, the 60% high fat diet (HFD) and the 58% high fat-high sucrose Surwit diet (HFHS) and their respective controls, were compared in C57BL/6J mice using glucose tolerance tests (IVGTT) and the euglycemic clamp. Results: Mice fed a HFD gained more weight than HFHS fed mice despite having similar energy intake. Both high fat diet models were glucose intolerant after eight weeks. Mice fed the HFD had elevated basal insulin, which was not seen in the HFHS group. The acute insulin response (AIR) was unchanged in the HFD group, but slightly increased in the HFHS diet group. The HFHS diet group had a threefold greater total insulin secretion during the IVGTT compared to its control, while no differences were seen in the HFD group. Insulin sensitivity was decreased fourfold in the HFD group, but not in the HFHS diet group. Conclusion: The HFD and HFHS diet models show differential effects on the development of insulin resistance and beta cell adaptation. These discrepancies are important to acknowledge in order to select the appropriate diet for specific studies. PMID:23201760

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

    USGS Publications Warehouse

    Brouxel, M.

    1991-01-01

    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.

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

    PubMed Central

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

    2013-01-01

    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

  3. Multiple forms of mouse antizyme inhibitor 1 mRNA differentially regulated by polyamines.

    PubMed

    Murakami, Yasuko; Ohkido, Makiko; Takizawa, Hiroko; Murai, Noriyuki; Matsufuji, Senya

    2014-03-01

    Antizyme inhibitor 1 (Azin1), a positive regulator of cellular polyamines, is induced by various proliferative stimuli and repressed by polyamines. It has been reported that the translational repression of Azin1 by polyamines involves an upstream open reading frame on the mRNA, but little has been known about polyamine effect on its transcription or splicing. We found multiple forms of Azin1 transcripts formed by alternative splicing and initiation of transcription from putative alternative start sites. One of the novel splice variants, Azin1-X, has a premature termination codon on 5? extension of exon 7, encodes a C-terminal truncated form of protein (Azin1?C), and is subject to nonsense-mediated mRNA decay. 2-Difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, increased both transcription from the canonical transcription start site and the ratio of the full-length mRNA to Azin1-X mRNA, whereas polyamines show the opposite effect. Thus, polyamines regulate two novel steps of Azin1 expression, namely the transcription and a particular splicing pattern, both of which may affect the level of mRNA encoding the full-length active Azin1 protein. PMID:24077669

  4. Differentiation between autism and multiple complex developmental disorder in response to psychosocial stress.

    PubMed

    Jansen, Lucres M C; Gispen-de Wied, Christine C; van der Gaag, Rutger-Jan; van Engeland, Herman

    2003-03-01

    Multiple Complex Developmental Disorder (MCDD) represents a distinct group within the autistic spectrum based on symptomatology. Unlike autistic children, part of MCDD children develop schizophrenia in adult life. Despite the differences, patients of both disorders are mainly characterized by abnormal reactions to their social environment. At the biological level, we showed in a previous study that MCDD children have a reduced cortisol response to psychosocial stress. Given the fact that autistic children clinically show more social impairments, it was hypothesized that they may have even further decreased cortisol responses to psychosocial stress than MCDD patients. Therefore, 10 autistic children were compared to 10 MCDD children and 12 healthy control children in their response to a psychosocial stressor, consisting of a public speaking task. In order to test whether any impairments in the biological stress response are specific for psychosocial stress, the autistic children were compared with 11 MCDD children and 15 control children in their response to a physical stressor, consisting of 10 min of bicycle exercise. Heart rate and salivary cortisol levels were used as indicators of response to the stress tests. Autistic children showed a relatively elevated cortisol response to psychosocial stress, in contrast to MCDD children who showed a reduced cortisol response. No differences in heart rate or cortisol responses to the physical stress test were found. The specific difference between autistic and MCDD children in their cortisol response to psychosocial stress indicates that the disturbed reactions to the social environment observed in these disorders may have different biological backgrounds. PMID:12629541

  5. Oxidative Stress Is Differentially Present in Multiple Sclerosis Courses, Early Evident, and Unrelated to Treatment

    PubMed Central

    Gironi, Maira; Borgiani, Bruno; Mariani, Enrica; Cursano, Cristina; Mendozzi, Laura; Cavarretta, Rossella; Saresella, Marina; Clerici, Mario; Comi, Giancarlo; Rovaris, Marco; Furlan, Roberto

    2014-01-01

    Background. Oxidative stress is well documented in multiple sclerosis (MS) lesions, but its correspondence at peripheral level is still controversial. Objective. To evaluate peripheral oxidative stress markers in MS patients. Methods. We studied total blood levels of Coenzyme Q10 (CoQ10), oxidized and reduced forms of glutathione, malondialdehyde, reactive oxygen species (ROS), anti-oxidized-low-density lipoproteins (anti-oxLDL) antibodies, and antioxidant power (PAO) in 87 patients with different MS clinical phenotypes and in 77 controls. Results. CoQ10 was lower whereas anti-oxLDL antibodies titer was higher in MS patients than in controls. The benign variant of MS displayed both higher CoQ10 and higher anti-oxLDL than other MS clinical variants. Female patients had lower CoQ10 and PAO and higher ROS than male patients. Differences were greater in younger patients with shorter disease duration. Surprisingly, there was no difference for these markers between treated and untreated patients. Conclusion. We found lower antioxidant agents and higher anti-oxLDL antibodies in MS, and the highest antibody titers occurred in the benign form. We suggest that natural anti-oxLDL antibodies can be protective against MS, saving blood brain barrier integrity. Our findings also suggest that milder MS is associated with a distinct oxidative stress pattern, which may provide a useful biomarker of disease prognosis. PMID:24741637

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

    PubMed

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

    2007-01-01

    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

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

    NASA Astrophysics Data System (ADS)

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

    2015-01-01

    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.

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

    NASA Astrophysics Data System (ADS)

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

    2014-11-01

    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.

  9. STABILITY OF MULTIPLICATION OPERATORS AND MULTIPLICATION

    E-print Network

    STABILITY OF MULTIPLICATION OPERATORS AND MULTIPLICATION SEMIGROUPS FATIH BAYAZIT, RETHA HEYMANN Abstract. We investigate uniform, strong, weak and almost weak stability of multiplication semigroups transform is that it converts a differential operator into a multiplication operator induced by some scalar

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

    E-print Network

    Meucci, Olimpia

    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

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

    NASA Astrophysics Data System (ADS)

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

    2013-10-01

    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.

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

    PubMed Central

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

    2013-01-01

    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. PMID:24154593

  13. Modeling multiple time scale firing rate adaptation in a neural network of local field potentials.

    PubMed

    Lundstrom, Brian Nils

    2015-02-01

    In response to stimulus changes, the firing rates of many neurons adapt, such that stimulus change is emphasized. Previous work has emphasized that rate adaptation can span a wide range of time scales and produce time scale invariant power law adaptation. However, neuronal rate adaptation is typically modeled using single time scale dynamics, and constructing a conductance-based model with arbitrary adaptation dynamics is nontrivial. Here, a modeling approach is developed in which firing rate adaptation, or spike frequency adaptation, can be understood as a filtering of slow stimulus statistics. Adaptation dynamics are modeled by a stimulus filter, and quantified by measuring the phase leads of the firing rate in response to varying input frequencies. Arbitrary adaptation dynamics are approximated by a set of weighted exponentials with parameters obtained by fitting to a desired filter. With this approach it is straightforward to assess the effect of multiple time scale adaptation dynamics on neural networks. To demonstrate this, single time scale and power law adaptation were added to a network model of local field potentials. Rate adaptation enhanced the slow oscillations of the network and flattened the output power spectrum, dampening intrinsic network frequencies. Thus, rate adaptation may play an important role in network dynamics. PMID:25319064

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

    PubMed

    Brown, Patrick; Calnan, Michael

    2013-05-01

    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

  15. Perceived stress in multiple sclerosis: the potential role of mindfulness in health and well-being.

    PubMed

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

    2014-04-01

    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. One hundred nineteen people with confirmed MS completed the Five-Facet Mindfulness Questionnaire, Perceived Stress Scale, Brief Coping Orientation for Problem Experiences, Connor-Davidson Resilience Scale, and Medical Outcome Study Short Form-36. Greater trait mindfulness was significantly associated with decreased psychological stress, better coping skills, increased resilience, and higher quality of life. After investigators controlled 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 well-being for those living with MS. PMID:24647090

  16. Multiple spike time patterns occur at bifurcation points of membrane potential dynamics.

    PubMed

    Toups, J Vincent; Fellous, Jean-Marc; Thomas, Peter J; Sejnowski, Terrence J; Tiesinga, Paul H

    2012-01-01

    The response of a neuron to repeated somatic fluctuating current injections in vitro can elicit a reliable and precisely timed sequence of action potentials. The set of responses obtained across trials can also be interpreted as the response of an ensemble of similar neurons receiving the same input, with the precise spike times representing synchronous volleys that would be effective in driving postsynaptic neurons. To study the reproducibility of the output spike times for different conditions that might occur in vivo, we somatically injected aperiodic current waveforms into cortical neurons in vitro and systematically varied the amplitude and DC offset of the fluctuations. As the amplitude of the fluctuations was increased, reliability increased and the spike times remained stable over a wide range of values. However, at specific values called bifurcation points, large shifts in the spike times were obtained in response to small changes in the stimulus, resulting in multiple spike patterns that were revealed using an unsupervised classification method. Increasing the DC offset, which mimicked an overall increase in network background activity, also revealed bifurcation points and increased the reliability. Furthermore, the spike times shifted earlier with increasing offset. Although the reliability was reduced at bifurcation points, a theoretical analysis showed that the information about the stimulus time course was increased because each of the spike time patterns contained different information about the input. PMID:23093916

  17. Improved Survival, Vascular Differentiation and Wound Healing Potential of Stem Cells Co-Cultured with Endothelial Cells

    PubMed Central

    Pedroso, Dora C. S.; Tellechea, Ana; Moura, Liane; Fidalgo-Carvalho, Isabel; Duarte, Joăo; Carvalho, Eugénia; Ferreira, Lino

    2011-01-01

    In this study, we developed a methodology to improve the survival, vascular differentiation and regenerative potential of umbilical cord blood (UCB)-derived hematopoietic stem cells (CD34+ cells), by co-culturing the stem cells in a 3D fibrin gel with CD34+-derived endothelial cells (ECs). ECs differentiated from CD34+ cells appear to have superior angiogenic properties to fully differentiated ECs, such as human umbilical vein endothelial cells (HUVECs). Our results indicate that the pro-survival effect of CD34+-derived ECs on CD34+ cells is mediated, at least in part, by bioactive factors released from ECs. This effect likely involves the secretion of novel cytokines, including interleukin-17 (IL-17) and interleukin-10 (IL-10), and the activation of the ERK 1/2 pathway in CD34+ cells. We also show that the endothelial differentiation of CD34+ cells in co-culture with CD34+-derived ECs is mediated by a combination of soluble and insoluble factors. The regenerative potential of this co-culture system was demonstrated in a chronic wound diabetic animal model. The co-transplantation of CD34+ cells with CD34+-derived ECs improved the wound healing relatively to controls, by decreasing the inflammatory reaction and increasing the neovascularization of the wound. PMID:21283630

  18. An alternative method for crack interaction in NDE of multiple cracks by means of potential drop technique

    Microsoft Academic Search

    R Ghajar

    2004-01-01

    A procedure of calculating the crack interaction in NDE of multiple cracks by d.c. potential drop technique is newly developed. This method can be used when the distances between cracks are small or large. The equations obtained evaluate crack interaction for any case regardless of the distances between the cracks. A subregion containing m (=1,3,5,…,) cracks are considered. The potential

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

    PubMed Central

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

    2013-01-01

    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

  20. Differential molecular profiling between skin carcinomas reveals four newly reported genes potentially implicated in squamous cell carcinoma development

    Microsoft Academic Search

    Claire Marionnet; Claude Lalou; Karine Mollier; Marjorie Chazal; Gisele Delestaing; Delphine Compan; Olivier Verola; Catherine Vilmer; Jerome Cuminet; Louis Dubertret; Nicole Basset-Séguin

    2003-01-01

    Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are skin tumors with different invasive potential. In this work, we analysed mRNA differential expression between seven BCC and five SCC and their normal skin counterparts using 1176 cDNA macroarrays and verification by RT–PCR to identify genes modulated in each tumor type. We identified 37 genes commonly modulated in both tumors

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

    SciTech Connect

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

    2011-10-03

    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.

  2. Effects of potential xenoestrogens (DEHP, nonylphenol and PCB) on sexual differentiation in juvenile Atlantic salmon ( Salmo salar)

    Microsoft Academic Search

    L. Norrgren; A. Blom; P. L. Andersson; H. Börjeson; D. G. J. Larsson; P.-E. Olsson

    1999-01-01

    The effects of 17?-estradiol and potential xenoestrogens were investigated on Atlantic salmon (Salmo salar). Juvenile salmon fed diets containing 15 and 30mg 17?-estradiol kg?1 food for 4weeks after yolk-sac resorption differentiated into 88 and 100% phenotypic females, respectively. The reference group, fed uncontaminated food, consisted of 49% females. A significant overrepresentation of phenotypic females (64%) was recorded in the group

  3. Gait Analysis at Multiple Speeds Reveals Differential Functional and Structural Outcomes in Response to Graded Spinal Cord Injury

    PubMed Central

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

    2014-01-01

    Abstract 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

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

    PubMed Central

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

    2014-01-01

    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

  5. Endocrine-committed progenitor cells retain their differentiation potential in the absence of neurogenin-3 expression.

    PubMed

    Prasadan, Krishna; Tulachan, Sidhartha; Guo, Ping; Shiota, Chiyo; Shah, Sohail; Gittes, George

    2010-06-11

    Neurogenin-3 (ngn-3) expression is critical for endocrine development in the developing pancreas. We found that when ngn-3 was inhibited in an E11.5 pancreas, using either morpholino antisense or siRNA, it led to a significant decrease in endocrine differentiation after seven days in culture. Endocrine differentiation was rescued when ngn-3 inhibition was withdrawn after three days of culture, suggesting that the embryonic pancreas retains progenitor cells with the ability to differentiate into endocrine cell types when ngn-3 expression recurs. To determine whether the rescue phenomenon observed after withdrawing ngn-3 antisense treatment was the result of the original endocrine-committed cells reinitiating endocrine differentiation, or was instead due to new recruitment of later progenitor cells, we blocked ngn-3 expression for only the last four days of a seven-day culture. Here, insulin-positive differentiation was slightly reduced, but there was a normal number of glucagon-positive cells. In addition, there was an increase in SOX9-positive cells in ngn-3 inhibited, as well as in ngn-3 rescued pancreata, with a significant proportion of these SOX9-positive cells co-localized with DBA, an early ductal marker. This increased number of cells with co-localization of SOX9 and DBA could indicate an increased number of endocrine progenitor cells. PMID:20471370

  6. Vestibular-evoked myogenic potentials: A method to assess vestibulo-spinal conduction in multiple sclerosis patients

    Microsoft Academic Search

    F Sartucci; F Logi

    2002-01-01

    Vestibular-evoked myogenic potentials (VEMPs), elicited by acoustic stimulation, have been proposed in the assessment of the vestibulo-cervical reflex pathways. The procedure has been previously validated in several otovestibular disorders. The aim of this study was to investigate patients affected by multiple sclerosis (MS) in the attempt to clarify the underlying physiopathogenetic mechanisms and the clinical utility of VEMPs in detecting

  7. Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple myeloma1

    E-print Network

    Paris-Sud XI, Université de

    1 Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis Tumorerkrankungen, INF350, D-69115 Heidelberg, Germany; Running title: Novel cancer-testis genes in multiple myeloma manuscript, published in "J Immunol 2009;183(2):832-40" DOI : 10.4049/jimmunol.0803298 #12;2 Abstract Cancer-testis

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

    ERIC Educational Resources Information Center

    Huffman, Celia A.

    2012-01-01

    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…

  9. 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

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

    2010-01-01

    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…

  10. Follicular lymphoma tumor–infiltrating T-helper (TH) cells have the same polyfunctional potential as normal nodal TH cells despite skewed differentiation

    PubMed Central

    Hilchey, Shannon P.; Rosenberg, Alexander F.; Hyrien, Ollivier; Secor-Socha, Shelley; Cochran, Matthew R.; Brady, Michael T.; Wang, Jyh-Chiang E.; Sanz, Ińaki; Burack, W. Richard; Quataert, Sally A.

    2011-01-01

    The follicular lymphoma (FL) T-cell microenvironment plays a critical role in the biology of this disease. We therefore determined the lineage, differentiation state, and functional potential of FL-infiltrating CD4+ T-helper cells (TH) compared with reactive and normal lymph node (NLN) TH cells. Relative to NLNs, FL cells have decreased proportions of naive and central memory but increased proportions of effector memory TH cells. We further show differences in the distribution and anatomical localization of CXCR5+ TH populations that, on the basis of transcription factor analysis, include both regulatory and follicular helper T cells. On Staphylococcus enterotoxin-B stimulation, which stimulates T cells through the T-cell receptor, requires no processing by APCs, and can overcome regulator T cell-mediated suppression, the proportion of uncommitted primed precursor cells, as well as TH2 and TH17 cells is higher in FL cells than in reactive lymph nodes or NLNs. However, the proportion of TH1 and polyfunctional TH cells (producing multiple cytokines simultaneously) is similar in FL cells and NLNs. These data suggest that, although TH-cell differentiation in FL is skewed compared with NLNs, FL TH cells should have the same intrinsic ability to elicit antitumor effector responses as NLN TH cells when tumor suppressive mechanisms are attenuated. PMID:21821704

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

    PubMed

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

    2015-07-01

    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. PMID:25560303

  12. Myeloma-specific multiple peptides able to generate cytotoxic T lymphocytes: A potential therapeutic application in multiple myeloma and other plasma cell disorders

    PubMed Central

    Bae, Jooeun; Smith, Robert; Daley, John; Mimura, Naoya; Tai, Yu-Tzu; Anderson, Kenneth C.; Munshi, Nikhil C.

    2013-01-01

    Purpose The efficacy of peptide vaccines may be enhanced by stimulating immune cells with multiple peptides derived from distinct tumor-associated antigens. We have evaluated the heteroclitic XBP1 US184–192 (YISPWILAV), heteroclitic XBP1 SP367–375 (YLFPQLISV), native CD138260–268 (GLVGLIFAV), and native CS1239–247 (SLFVLGLFL) peptides, which have strong HLA-A2 affinity and immunogenicity in combination, for their ability to elicit multiple myeloma antigen-specific responses. Experimental Design Multipeptide-specific cytotoxic T lymphocytes (MP-CTL) were generated by the stimulation of CD3+ T lymphocytes from HLA-A2+ individuals with either autologous mature dendritic cells or T2 cells pulsed with a cocktail of these four peptides. Results The peptide cocktail did not compromise tumor antigen-specific activity of CTL. MP-CTL displayed increased total, effector memory (CCR7?CD45RO+), and activated (CD69+) CD3+CD8+ T lymphocytes. In addition, MP-CTL demonstrated IFN-? production, cell proliferation, and cytotoxicity against HLA-A2+ multiple myeloma cells, including HLA-A2+ MM patients’ cells. Importantly, MP-CTL showed specific responses in functional assays to each relevant peptide, but not to an irrelevant HLA-A2 specific CMV pp65 (NLVPMVATV) peptide. Conclusions These results highlight the potential therapeutic application of vaccination with a cocktail of HLA-A2 specific peptides to induce CTL with a broad spectrum of immune responses against multiple myeloma antigens. PMID:22753586

  13. Potential Benefits of Nintendo Wii Fit Among People with Multiple Sclerosis

    PubMed Central

    Finlayson, Marcia

    2011-01-01

    We examined the potential of Nintendo Wii Fit (Nintendo Co, Ltd, Kyoto, Japan) to increase physical activity (PA) behavior and health among people with multiple sclerosis (MS). The study consisted of a repeated-measures design with a baseline control period and involved 30 people with MS who had the ability to walk 25 feet with or without a cane (26 individuals were included in the analyses). Nintendo Wii was set up in the homes of participants, who were prescribed a Wii Fit exercise program lasting 14 weeks, 3 days a week. The Physical Activity and Disability Survey, Modified Fatigue Impact Scale, and 36-item Short Form Health Status Survey were administered three times before participants gained access to Wii Fit (control period, at 2-week intervals), and three times after they received Wii Fit (posttest 1: immediately after; posttest 2: 7 weeks after; posttest 3: 14 weeks after). Mobility, balance, strength, and weight were assessed at the first pretest, immediately prior to obtaining access to Wii Fit, and 7 weeks after obtaining access to Wii Fit. Results from the questionnaires indicated that PA significantly improved at week 7, but at week 14, PA levels declined relative to week 7 and the difference was no longer significant compared with the control period. Physical assessments indicated that balance and strength significantly improved at week 7. One adverse event was reported (repetitive knee injury). Physical assessments indicated that people with MS may be able to improve their fitness levels by using Wii Fit. Future studies should incorporate behavior change strategies to promote long-term use of Wii Fit, and explore whether individuals with more severe symptoms of MS can safely use Wii Fit. PMID:24453702

  14. Nuclear receptors and autoimmune disease: the potential of PPAR agonists to treat multiple sclerosis.

    PubMed

    Racke, Michael K; Gocke, Anne R; Muir, Mark; Diab, Asim; Drew, Paul D; Lovett-Racke, Amy E

    2006-03-01

    Experimental autoimmune encephalomyelitis (EAE) is a T-cell-mediated, autoimmune disorder characterized by central nervous system inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). Prior work in the EAE model has suggested that encephalitogenic T cells are of the T helper (Th)-1 phenotype. Our group has performed several studies in the EAE model that suggest that a strategy for treating autoimmune disorders is to convert the pathogenic cells from the Th1 to Th2 phenotype. Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear hormone receptor superfamily that include receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Recently, we examined the role of PPARgamma in EAE and observed that administration of the PPARgamma agonist 15-deoxy-Delta(12,14) prostaglandin J2 exerted a significant therapeutic effect predominantly by inhibiting the activation and expansion of encephalitogenic T cells. One potential advantage in studying PPARalpha agonists is that they have been very well tolerated when used in humans to treat conditions such as elevated triglycerides. Building on prior work in immune deviation and with PPAR agonists, we have demonstrated that PPARalpha agonists can alter the cytokine phenotype of myelin-reactive T cells, alter their encephalitogenicity, and be useful in the treatment of EAE. The fact that PPARalpha agonists have been used as therapeutic agents in humans to treat metabolic conditions for over 25 years with little toxicity makes them attractive candidates for use as adjunctive therapies in MS. PMID:16484546

  15. Vestibular-evoked myogenic potentials, clinical evaluation, and imaging findings in multiple sclerosis.

    PubMed

    Güven, Hayat; Bay?r, Omer; Aytaç, Emrah; Ozdek, Ali; Como?lu, Selim Selçuk; Korkmaz, Hakan

    2014-02-01

    Vestibular-evoked myogenic potentials (VEMP), short-latency electromyographic responses elicited by acoustic stimuli, evaluate the function of vestibulocollic reflex and may give information about brainstem function. The aim of the present study is to evaluate the potential contribution of VEMP to the diagnosis of multiple sclerosis (MS). Fifty patients with MS and 30 healthy control subjects were included in this study. The frequency of VEMP p1-n1 and n2-p2 waves; mean p1, n1, n2, and p2 latency; and mean p1-n1 and n2-p2 amplitude were determined. The relation between clinical and imaging findings and VEMP parameters was evaluated. The p1-n1 and n2-p2 waves were more frequently absent in MS than in control subjects [p1-n1 wave absent: MS, 25 (25 %) ears; control, 6 (10 %) ears; P ? 0.02] [n2-p2 wave absent: MS, 44 (44 %) ears; control, 7 (12 %) ears; P ? 0.001]. The mean p1-n1 amplitude was lower in MS than in control subjects (MS, 19.1 ± 7.2 ?V; control, 23.3 ± 7.4 ?V; P ? 0.002). A total of 24/50 (48 %) MS patients had VEMP abnormalities (absent responses and/or prolonged latencies). VEMP abnormalities were more frequent in patients with than without vestibular symptoms (P ? 0.02) and with brainstem functional system score (FSS) ? 1 than FSS = 0 (P ? 0.02). In patients with MS, absence of p1-n1 wave was more frequent in patients with than without vestibular symptoms [absence of p1-n1 wave: vestibular symptoms, 9 (45 %) ears; no vestibular symptoms, 16 (20 %) ears; P ? 0.03] and patients with Expanded Disability Status Scale (EDSS) score ? 5.5 [absence of p1-n1 wave: EDSS ? 5.5, 7 (70 %) ears; EDSS <5.5, 18 (20 %) ears; P ? 0.001]. Abnormal VEMP may be noted in MS patients, especially those with vestibular symptoms and greater disability. The VEMP test may complement other studies for diagnosis and follow-up of patients with MS. PMID:23807120

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

    Microsoft Academic Search

    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

    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

  17. Automotive fuel economy - potential improvement through selected engine and differential gear lubricants. Final report

    Microsoft Academic Search

    Naman

    1981-01-01

    This report evaluates the effects of four engine lubricants and three differential gear lubricants on the fuel economy of two 1978 automobiles operated at 20F, 70F, and 100F ambient temperatures. The engine lubricants were evaluated using the 1978 Federal Test procedure and steady state tests from a cold start. The gear lubricants were evaluated in steady state operation from a

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

    Microsoft Academic Search

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

    2009-01-01

    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

  19. A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential

    Microsoft Academic Search

    Gesine Kögler; Sandra Sensken; Judith A. Airey; Thorsten Trapp; Markus Müschen; Niklas Feldhahn; Stefanie Liedtke; Rüdiger V. Sorg; Johannes Fischer; Claudia Rosenbaum; Susanne Greschat; Andreas Knipper; Jörg Bender; Özer Degistirici; Jizong Gao; Arnold I. Caplan; Evan J. Colletti; Graça Almeida-Porada; Hans W. Müller; Esmail Zanjani; Peter Wernet

    2004-01-01

    Here a new, intrinsically pluripotent, CD45-negative population from human cord blood, termed unrestricted somatic stem cells (USSCs) is described. This rare population grows adher- ently and can be expanded to 10 15 cells without losing pluripotency. In vitro USSCs showed homogeneous differentiation into osteoblasts, chondroblasts, adipocytes, and hematopoietic and neural cells including astrocytes and neurons that express neurofilament, sodium channel

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

    PubMed

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

    2010-04-01

    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

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

    PubMed Central

    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

    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

  2. 5-Azacytidine Improves the Osteogenic Differentiation Potential of Aged Human Adipose-Derived Mesenchymal Stem Cells by DNA Demethylation

    PubMed Central

    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

    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

  3. Identification of New Differentially Methylated Genes That Have Potential Functional Consequences in Prostate Cancer

    PubMed Central

    Kim, Jin W.; Kim, Seong-Tae; Turner, Aubrey R.; Young, Tracey; Smith, Shelly; Liu, Wennuan; Lindberg, Johan; Egevad, Lars; Gronberg, Henrik; Isaacs, William B.; Xu, Jianfeng

    2012-01-01

    Many differentially methylated genes have been identified in prostate cancer (PCa), primarily using candidate gene-based assays. Recently, several global DNA methylation profiles have been reported in PCa, however, each of these has weaknesses in terms of ability to observe global DNA methylation alterations in PCa. We hypothesize that there remains unidentified aberrant DNA methylation in PCa, which may be identified using higher resolution assay methods. We used the newly developed Illumina HumanMethylation450 BeadChip in PCa (n?=?19) and adjacent normal tissues (n?=?4) and combined these with gene expression data for identifying new DNA methylation that may have functional consequences in PCa development and progression. We also confirmed our methylation results in an independent data set. Two aberrant DNA methylation genes were validated among an additional 56 PCa samples and 55 adjacent normal tissues. A total 28,735 CpG sites showed significant differences in DNA methylation (FDR adjusted P<0.05), defined as a mean methylation difference of at least 20% between PCa and normal samples. Furthermore, a total of 122 genes had more than one differentially methylated CpG site in their promoter region and a gene expression pattern that was inverse to the direction of change in DNA methylation (e.g. decreased expression with increased methylation, and vice-versa). Aberrant DNA methylation of two genes, AOX1 and SPON2, were confirmed via bisulfate sequencing, with most of the respective CpG sites showing significant differences between tumor samples and normal tissues. The AOX1 promoter region showed hypermethylation in 92.6% of 54 tested PCa samples in contrast to only three out of 53 tested normal tissues. This study used a new BeadChip combined with gene expression data in PCa to identify novel differentially methylated CpG sites located within genes. The newly identified differentially methylated genes may be used as biomarkers for PCa diagnosis. PMID:23119026

  4. On Differential Expressions with {delta}-Potential: Exceptional Case d 2l

    SciTech Connect

    Antonevich, A. [University of Bialystok, Akademicka 2 Bialystok, Poland, Belarussian State University, Minsk (Belarus)

    2010-11-25

    The paper is devoted to the study of the formal differential expressions (-{Delta}){sup l}u+a{delta}u for arbitrary l(set-membership sign)N and the dimension of R{sup d} equal d = 2l. Approximations of the singular part by means of a family of rank-one operators are constructed and resolvent convergence of this family is investigated. It is demonstrated that the results are different from the case d{ne}2l.

  5. Automotive fuel economy - potential improvement through selected engine and differential gear lubricants. Final report

    SciTech Connect

    Naman, T.M.

    1981-07-01

    This report evaluates the effects of four engine lubricants and three differential gear lubricants on the fuel economy of two 1978 automobiles operated at 20F, 70F, and 100F ambient temperatures. The engine lubricants were evaluated using the 1978 Federal Test procedure and steady state tests from a cold start. The gear lubricants were evaluated in steady state operation from a cold start.

  6. Reliability: Arguments for Multiple Perspectives and Potential Problems with Generalization across Studies.

    ERIC Educational Resources Information Center

    Dimitrov, Dimiter M.

    2002-01-01

    Discusses reliability issues in light of recent studies and debates focused on psychometrics versus datametrics terminology and reliabilities generalization. Discusses the way multiple perspectives on score reliability may affect research practice, editorial policies, and reliability generalization across studies. (SLD)

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

    PubMed Central

    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

    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

  8. Multiple bottom-simulating reflections in the Black Sea: Potential proxies of past climate conditions

    Microsoft Academic Search

    Irina Popescu; Marc De Batist; Gilles Lericolais; Hervé Nouzé; Jeffrey Poort; Nicolae Panin; Wim Versteeg; Hervé Gillet

    2006-01-01

    A previously unknown pattern of multiple bottom-simulating reflections (BSRs) occurs on high-resolution reflection seismic data in the Danube deep-sea fan, associated with acoustic features indicating free gas. Our study provides evidence that this pattern is developed in relation with the architecture of distinct channel–levee systems of the Danube fan. Channel–levee systems hosting multiple BSRs act as relatively sealed gas-bearing systems

  9. Two Heteromeric Kv1 Potassium Channels Differentially Regulate Action Potential Firing

    Microsoft Academic Search

    Paul D. Dodson; Matthew C. Barker; Ian D. Forsythe

    2002-01-01

    Low-threshold voltage-gated potassium currents (ILT ) activat- ing close to resting membrane potentials play an important role in shaping action potential (AP) firing patterns. In the medial nucleus of the trapezoid body (MNTB), ILT ensures generation of single APs during each EPSP, so that the timing and pattern of AP firing is preserved on transmission across this relay synapse (calyx

  10. Information processing speed, neural efficiency, and working memory performance in multiple sclerosis: differential relationships with structural magnetic resonance imaging.

    PubMed

    Covey, Thomas J; Zivadinov, Robert; Shucard, Janet L; Shucard, David W

    2011-12-01

    Multiple sclerosis (MS), a central nervous system (CNS) neurodegenerative disorder, involves lesions of both white and gray matter and reported cognitive impairments that include processing speed (PS), executive function, and working memory (WM). This study closely examined the specifics of these cognitive deficits and their relationship to structural brain damage. A visual n-back task with 3 WM load conditions was used to assess WM performance (task accuracy), PS (reaction time, RT), and a novel measure of processing efficiency (standard deviation of RT, RTSD) in MS patients and controls. These behavioral measures were related to quantitative magnetic resonance imaging (MRI) measures of white and gray matter integrity. Even when MS patients performed as well as controls, as seen for low WM load (0-back), they responded more slowly and were less efficient in their speed of responding. Accuracy findings indicated that the correct match trials were superior to correct nonmatch trials at differentiating MS patients from controls. Further, decreased accuracy during the highest WM load condition was associated with global damage that included both gray and white matter atrophy, while slowed PS and particularly processing inefficiency were associated primarily with white matter atrophy in MS. Importantly, relationships between PS, processing efficiency, performance accuracy, and structural MRI measures were seen only during the highest WM load condition, the condition that required the most executive control. These findings suggest that the MRI/behavioral relationships that were present exclusively during the 2-back condition may reflect connectivity involving frontal cortical systems, the site for executive control. PMID:22047454

  11. Measurements of jet multiplicity and differential production cross sections of Z + jets events in proton-proton collisions at sqrt(s) = 7 TeV

    E-print Network

    CMS Collaboration

    2015-03-16

    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 sqrt(s) = 7 TeV, recorded by the CMS detector, using a data sample corresponding to an integrated luminosity of 4.9 inverse femtobarns. 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.

  12. Differential molecular profiling between skin carcinomas reveals four newly reported genes potentially implicated in squamous cell carcinoma development.

    PubMed

    Marionnet, Claire; Lalou, Claude; Mollier, Karine; Chazal, Marjorie; Delestaing, Gisele; Compan, Delphine; Verola, Olivier; Vilmer, Catherine; Cuminet, Jerome; Dubertret, Louis; Basset-Séguin, Nicole

    2003-05-29

    Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are skin tumors with different invasive potential. In this work, we analysed mRNA differential expression between seven BCC and five SCC and their normal skin counterparts using 1176 cDNA macroarrays and verification by RT-PCR to identify genes modulated in each tumor type. We identified 37 genes commonly modulated in both tumors and four genes specifically modulated in SCC. Among these latter RhoC and EMMPRIN genes seem to be of particular interest and could participate in SCC aggressivity. PMID:12776202

  13. Electroosmotic Flow in Rectangular Nanochannels with Variable Wall potential: Generation of Multiple Nano-Vortices

    Microsoft Academic Search

    Lei Chen

    2005-01-01

    Electroosmotic flow in nanochannels is characterized by a very small Reynolds number so that mixing is difficult. While several researchers have presented results for the case of periodic wall potential, and for a sudden change in potential there has been no systematic study of the effect of the variation of wall potential on the flow structure. We have calculated the

  14. Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques

    PubMed Central

    Simon, Liz; LeCapitaine, Nicole; Berner, Paul; Vande Stouwe, Curtis; Mussell, Jason C.; Allerton, Timothy; Primeaux, Stefany D.; Dufour, Jason; Nelson, Steve; Bagby, Gregory J.; Cefalu, William

    2014-01-01

    Chronic alcohol abuse is associated with skeletal muscle myopathy. Previously, we demonstrated that chronic binge alcohol (CBA) consumption by rhesus macaques accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus (SIV) infection. A proinflammatory, prooxidative milieu and enhanced ubiquitin proteasome activity were identified as possible mechanisms leading to loss of skeletal muscle. The possibility that impaired regenerative capacity, as reflected by the ability of myoblasts derived from satellite cell (SCs) to differentiate into myotubes has not been examined. We hypothesized that the inflammation and oxidative stress in skeletal muscle from CBA animals impair the differentiation capacity of myoblasts to form new myofibers in in vitro assays. We isolated primary myoblasts from the quadriceps femoris of rhesus macaques that were administered CBA or isocaloric sucrose (SUC) for 19 mo. Proliferation and differentiation potential of cultured myoblasts were examined in vitro. Myoblasts from the CBA group had significantly reduced PAX7, MYOD1, MYOG, MYF5, and MEF2C expression. This was associated with decreased myotube formation as evidenced by Jenner-Giemsa staining and myonuclei fusion index. No significant difference in the proliferative ability, cell cycle distribution, or autophagy was detected between myoblasts isolated from CBA and SUC groups. Together, these results reflect marked dysregulation of myoblast myogenic gene expression and myotube formation, which we interpret as evidence of impaired skeletal muscle regenerative capacity in CBA-administered macaques. The contribution of this mechanism to alcoholic myopathy warrants further investigation. PMID:24671243

  15. Chronic binge alcohol consumption alters myogenic gene expression and reduces in vitro myogenic differentiation potential of myoblasts from rhesus macaques.

    PubMed

    Simon, Liz; LeCapitaine, Nicole; Berner, Paul; Vande Stouwe, Curtis; Mussell, Jason C; Allerton, Timothy; Primeaux, Stefany D; Dufour, Jason; Nelson, Steve; Bagby, Gregory J; Cefalu, William; Molina, Patricia E

    2014-06-01

    Chronic alcohol abuse is associated with skeletal muscle myopathy. Previously, we demonstrated that chronic binge alcohol (CBA) consumption by rhesus macaques accentuates skeletal muscle wasting at end-stage of simian immunodeficiency virus (SIV) infection. A proinflammatory, prooxidative milieu and enhanced ubiquitin proteasome activity were identified as possible mechanisms leading to loss of skeletal muscle. The possibility that impaired regenerative capacity, as reflected by the ability of myoblasts derived from satellite cell (SCs) to differentiate into myotubes has not been examined. We hypothesized that the inflammation and oxidative stress in skeletal muscle from CBA animals impair the differentiation capacity of myoblasts to form new myofibers in in vitro assays. We isolated primary myoblasts from the quadriceps femoris of rhesus macaques that were administered CBA or isocaloric sucrose (SUC) for 19 mo. Proliferation and differentiation potential of cultured myoblasts were examined in vitro. Myoblasts from the CBA group had significantly reduced PAX7, MYOD1, MYOG, MYF5, and MEF2C expression. This was associated with decreased myotube formation as evidenced by Jenner-Giemsa staining and myonuclei fusion index. No significant difference in the proliferative ability, cell cycle distribution, or autophagy was detected between myoblasts isolated from CBA and SUC groups. Together, these results reflect marked dysregulation of myoblast myogenic gene expression and myotube formation, which we interpret as evidence of impaired skeletal muscle regenerative capacity in CBA-administered macaques. The contribution of this mechanism to alcoholic myopathy warrants further investigation. PMID:24671243

  16. Event-related brain potentials differentiate positive and negative mood adjectives during both supraliminal and subliminal visual processing.

    PubMed

    Bernat, E; Bunce, S; Shevrin, H

    2001-08-01

    This experiment provides brain event-related potential (ERP) evidence for differential processing of visually presented pleasant and unpleasant affectively valent words (mood adjectives) for both supraliminal (40 ms) and subliminal (unmasked, 1 ms) stimulus durations. Unpleasant words elicited a more positive amplitude than pleasant words in both durations. ERP components (P1, N1, P2, P3, and a late positive potential; LP) were measured at six electrode sites (F3, F4, P3, P4, CzPz, Oz). ERPs to subliminal stimuli demonstrated differences between pleasant and unpleasant words in the left hemisphere across all measured components. Supraliminal processing showed similar differences in the left hemisphere for early components (P1 and N1), but bilateral differences for late components (P3 and LP). Activity in the P2 time window was associated with the divergence between supraliminal and subliminal affective responses. Implications for the study of affect and consciousness are discussed. PMID:11451477

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

    E-print Network

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

    2012-06-07

    : Dendritic cells and the control of immunity. Nature 1998, 392:245-252. 67. Vaknin-Dembinsky A, Balashov K, Weiner HL: IL-23 is increased in dendritic cells in multiple sclerosis and down-regulation of IL-23 by antisense oligos increases dendritic cell IL-10...

  18. Potential of a unique antibody gene signature to predict conversion to clinically definite multiple sclerosis

    Microsoft Academic Search

    Elizabeth M. Cameron; Sade Spencer; Jonathan Lazarini; Christopher T. Harp; E. Sally Ward; Mark Burgoon; Gregory P. Owens; Michael K. Racke; Jeffrey L. Bennett; Elliot M. Frohman; Nancy L. Monson

    2009-01-01

    We identified a unique antibody gene mutation pattern (i.e. “signature”) in cerebrospinal fluid (CSF) B cells from multiple sclerosis (MS) patients not present in control populations. Prevalence of the signature in CSF B cells of patients at risk to develop MS predicted conversion to MS with 91% accuracy in a small cohort of clinically isolated syndrome patients. If confirmed, signature

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

    SciTech Connect

    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

    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.

  20. Differential potential for envelope glycoprotein-mediated steric shielding of host cell surface proteins among filoviruses.

    PubMed

    Noyori, Osamu; Matsuno, Keita; Kajihara, Masahiro; Nakayama, Eri; Igarashi, Manabu; Kuroda, Makoto; Isoda, Norikazu; Yoshida, Reiko; Takada, Ayato

    2013-11-01

    The viral envelope glycoprotein (GP) is thought to play important roles in the pathogenesis of filovirus infection. It is known that GP expressed on the cell surface forms a steric shield over host proteins such as major histocompatibility complex class I and integrin ?1, which may result in the disorder of cell-to-cell contacts and/or inhibition of the immune response. However, it is not clarified whether this phenomenon contributes to the pathogenicity of filoviruses. In this study, we found that the steric shielding efficiency differed among filovirus strains and was correlated with the difference in their relative pathogenicities. While the highly glycosylated mucin-like region of GP was indispensable, the differential shielding efficiency did not necessarily depend on the primary structure of the mucin-like region, suggesting the importance of the overall properties (e.g., flexibility and stability) of the GP molecule for efficient shielding of host proteins. PMID:24074577

  1. Multiple negative differential resistance devices with ultra-high peak-to-valley current ratio for practical multi-valued logic and memory applications

    NASA Astrophysics Data System (ADS)

    Shin, Sunhae; Rok Kim, Kyung

    2015-06-01

    In this paper, we propose a novel multiple negative differential resistance (NDR) device with ultra-high peak-to-valley current ratio (PVCR) over 106 by combining tunnel diode with a conventional MOSFET, which suppresses the valley current with transistor off-leakage level. Band-to-band tunneling (BTBT) in tunnel junction provides the first peak, and the second peak and valley are generated from the suppression of diffusion current in tunnel diode by the off-state MOSFET. The multiple NDR curves can be controlled by doping concentration of tunnel junction and the threshold voltage of MOSFET. By using complementary multiple NDR devices, five-state memory is demonstrated only with six transistors.

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

    USGS Publications Warehouse

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

    2005-01-01

    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.

  3. A multiple scattering theory approach to solving the time-dependent Schrödinger equation with an asymmetric rectangular potential

    E-print Network

    Victor F. Los; Nicholas V. Los

    2015-06-29

    An exact time-dependent solution for the wave function $\\psi(r,t)$ of a particle moving in the presence of an asymmetric rectangular well/barrier potential varying in one dimension is obtained by applying a novel for this problem approach using multiple scattering theory (MST) for the calculation of the space-time propagator. This approach, based on the localized at the potential jumps effective potentials responsible for transmission through and reflection from the considered rectangular potential, enables considering these processes from a particle (rather than a wave) point of view. The solution describes these quantum phenomena as a function of time and is related to the fundamental issues (such as measuring time) of quantum mechanics. It is presented in terms of integrals of elementary functions and is a sum of the forward- and backward-moving components of the wave packet. The relative contribution of these components and their interference as well as of the potential asymmetry to the probability density $|\\psi(x,t)|^2$ and particle dwell time is considered and numerically visualized for narrow and broad energy (momentum) distributions of the initial Gaussian wave packet. The obtained solution is also related to the kinetic theory of nanostructures due to the fact that the considered potential can model the spin-dependent potential profile of the magnetic multilayers used in spintronics devices.

  4. Potential Field Approach to Ensure Connectivity and Differentiated Detection in WSN Deployment

    Microsoft Academic Search

    Nadjib Aitsaadi; Nadjib Achir; Khaled Boussetta; Guy Pujolle

    2009-01-01

    This paper addresses the issue of wireless sensor network (WSN) deployment. We investigate this problem in the case where the monitored area is characterized by a geographical irregularity of the sensed events. Precisely, we consider that each point of the deployment area requires a minimum threshold guarantee on the event detection probability. Our proposed scalable deployment method, named potential field-based

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

    ERIC Educational Resources Information Center

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

    2010-01-01

    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…

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

    E-print Network

    Bongarzone, Ernesto R.

    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

  7. Differential processing of social chemosignals obtained from potential partners in regards to gender and sexual orientation.

    PubMed

    Lübke, Katrin T; Hoenen, Matthias; Pause, Bettina M

    2012-03-17

    On an individual level, human body odors carry information about whether a person is an eligible mate. The current studies investigate if body odors also transmit information about individuals being potential partners in more general terms, namely in regards to gender and sexual orientation. In study 1, 14 gay and 14 heterosexual men were presented with body odors obtained from potential partners (gay male and heterosexual female body odors, respectively) and heterosexual male body odor as a control. In study 2, 14 lesbian and 14 heterosexual women were presented with lesbian female and heterosexual male body odors representing body odors of potential partners, and heterosexual female body odor as a control. Central nervous processing was analyzed using chemosensory event-related potentials and current source density analysis (64-channel EEG recording). Gay and heterosexual men responded with shorter P2 latencies to the body odors of their preferred sexual partners, and lesbian women responded with shorter P2 latencies to body odors of their preferred gender. In response to heterosexual male body odors, lesbian women displayed the most pronounced P3 amplitude, and distinct neuronal activation in medial frontal and parietal neocortical areas. A similar pattern of neuronal activation was observed in gay men when presented with heterosexual male body odor. Both the early processing advantage (P2) for desirable partners' body odors as well as the enhanced evaluative processing (P3, CSD) of undesirable partners' body odors suggest that human body odors indeed carry information about individuals being potential partners in terms of gender and sexual orientation. PMID:22197679

  8. The normal matrix model with a monomial potential, a vector equilibrium problem, and multiple orthogonal polynomials on a star

    NASA Astrophysics Data System (ADS)

    Kuijlaars, Arno B. J.; López-García, Abey

    2015-02-01

    We investigate the asymptotic behaviour of a family of multiple orthogonal polynomials that is naturally linked with the normal matrix model with a monomial potential of arbitrary degree d + 1. The polynomials that we investigate are multiple orthogonal with respect to a system of d analytic weights defined on a symmetric (d + 1)-star centred at the origin. In the first part we analyse in detail a vector equilibrium problem involving a system of d interacting measures (?1, …, ?d) supported on star-like sets in the plane. We show that in the subcritical regime, the first component ?1* of the solution to this problem is the asymptotic zero distribution of the multiple orthogonal polynomials. It also characterizes the domain where the eigenvalues in the normal matrix model accumulate, in the sense that the Schwarz function associated with the boundary of this domain can be expressed explicitly in terms of ?1* . The second part of the paper is devoted to the asymptotic analysis of the multiple orthogonal polynomials. The asymptotic results are obtained again in the subcritical regime, and they follow from the Deift/Zhou steepest descent analysis of a Riemann–Hilbert problem of size (d + 1) × (d + 1). The vector equilibrium problem and the Riemann–Hilbert problem that we investigate are generalizations of those studied recently by Bleher–Kuijlaars in the case d = 2.

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

    PubMed Central

    Andreu-Vieyra, Claudia V.

    2014-01-01

    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

  10. Bone Marrow Angiogenesis and Plasma Cell Angiogenic and Invasive Potential in Patients with Active Multiple Myeloma

    Microsoft Academic Search

    Angelo Vacca; Domenico Ribatti; Aldo M. Roccaro; Roberto Ria; Loredana Palermo; Franco Dammacco

    2001-01-01

    Factor VIII-related antigen-positive microvessel areas were measured by both immunohistochemistry and computerized image analysis in patients with active multiple myeloma (MM), nonactive MM and monoclonal gammopathies of undetermined significance (MGUS). A 5- to 6-fold larger area was found in patients with active MM compared to the other two groups. The conditioned medium (CM) of their bone marrow plasma cells stimulated

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

    PubMed

    Andreu-Vieyra, Claudia V; Berenson, James R

    2014-12-01

    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

  12. UNAIDS 'multiple sexual partners' core indicator: promoting sexual networks to reduce potential biases.

    PubMed

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

    2014-01-01

    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

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

    PubMed Central

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

    2014-01-01

    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

  14. Evaluation of the cytotoxic and inflammatory potential of differentially shaped zinc oxide nanoparticles

    Microsoft Academic Search

    Boon Chin Heng; Xinxin Zhao; Eng Chok Tan; Nurulain Khamis; Aarti Assodani; Sijing Xiong; Christiane Ruedl; Kee Woei Ng; Joachim Say-Chye Loo

    Zinc oxide (ZnO) nanoparticles have wide-ranging applications in a diverse array of industrial and consumer products, from\\u000a ceramic manufacture and paint formulation to sunscreens and haircare products. Hence, it is imperative to rigorously characterize\\u000a the health and safety aspects of human exposure to ZnO nanoparticles. This study therefore evaluated the cellular association,\\u000a cytotoxic and inflammatory potential of spherical and sheet-shaped

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

    Microsoft Academic Search

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

    2008-01-01

    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

  16. Nuclear Reprogramming Strategy Modulates Differentiation Potential of Induced Pluripotent Stem Cells

    Microsoft Academic Search

    Almudena Martinez-Fernandez; Timothy J. Nelson; Andre Terzic

    2011-01-01

    Bioengineered by ectopic expression of stemness factors, induced pluripotent stem (iPS) cells demonstrate embryonic stem cell-like\\u000a properties and offer a unique platform for derivation of autologous pluripotent cells from somatic tissue sources. In the\\u000a process of nuclear reprogramming, somatic tissues are converted to a pluripotent ground state, thus unlocking an unlimited\\u000a potential to expand progenitor pools. Molecular dissection of nuclear

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

    PubMed

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

    2015-03-01

    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-naďve 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

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

    PubMed Central

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

    2014-01-01

    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 musculus129 × 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

  19. Exome analysis resolves differential diagnosis of familial kidney disease and uncovers a potential confounding variant.

    PubMed

    Gibson, Jane; Gilbert, Rodney D; Bunyan, David J; Angus, Elizabeth M; Fowler, Darren J; Ennis, Sarah

    2013-12-01

    A girl aged 6 presented with haematuria and her sister (aged 5) presented with haematuria and proteinuria. Family history showed multiple individuals suffering from end stage renal failure from the paternal side of the pedigree. Following kidney biopsy in the father and paternal grandmother, the pathological diagnosis was of focal segmental glomerulosclerosis (FSGS). Exome sequencing was undertaken in the proband's sister and grandmother. Genetic variants shared by both affected individuals were interrogated to identify the genetic cause of disease. Candidate variants were then sequenced in all the family members to determine segregation with the disease. A mutation of COL4A5 known to cause Alport syndrome segregated with disease from the paternal side of the pedigree and a variant in NPHS1 was present in both paediatric cases and inherited from their mother. This study highlights the advantages of exome sequencing over single gene testing; disease presentation can be heterogeneous with several genes representing plausible candidates; candidate gene(s) may be unavailable as a diagnostic test; consecutive, single gene testing typically concludes once a single causal mutation is identified. In this family, we were able to confirm a diagnosis of Alport syndrome, which will facilitate testing in other family members. PMID:24472419

  20. The distal sensory nerve action potential as a diagnostic tool for the differentiation of lesions in dorsal roots and peripheral nerves

    Microsoft Academic Search

    R. Benecke; B. Conrad

    1980-01-01

    On the basis of the conception that, in preganglionic lesions, peripheral sensory nerve fibers should remain intact, the question arises whether evaluation of distal sensory nerve action potentials can be helpful in differentiating between cervical dorsal root and peripheral nerve lesions. Amplitudes of sensory nerve action potentials (SNAP) and corresponding distal sensory conduction velocities (SCV) of the median and ulnar

  1. Comparison of proliferative and multilineage differentiation potentials of cord matrix, cord blood, and bone marrow mesenchymal stem cells

    PubMed Central

    Shetty, Prathibha; Cooper, Khushnuma; Viswanathan, Chandra

    2010-01-01

    Background: Hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs) are the two widely studied and characterized adult stem cells. Thus far, MSCs were obtained from the bone marrow, which is a painful procedure. Therefore, MSCs from less common sources like cord blood, adipose tissue, tooth pulp, and so on, have been the subject of research. The purpose of this study is to explore the possibility of finding MSCs from a less controversial, easy, and abundant source, such as the umbilical cord, for potential regenerative medicine applications. Study Design and Methods: Five bone marrow samples (BM), seventy cord blood units (CB), and four umbilical cord matrix (CM) samples have been used for the study. Expanded MSCs were checked for biomarker expression by flow cytometry and were also checked for their differentiation to mesodermal and ectodermal lineages. Results: MSCs could be isolated from 100% BM and CM samples, as compared to only 6% of CB samples. The fold expansion of the mesenchymal stem cells observed in CB (CB-MSCs) was distinctly higher as compared to BM (BM-MSCs) and CM (CM-MSCs). MSCs isolated from all the three sources expressed a characteristic mesenchymal phenotype of CD45 ? /vWF ? /CD14 ? /CD31 ? /CD73 + /CD105 + /SSEA4 + /CD29 + /CD44 + /HLAABC +, whereas, the HLA DR was conspicuously absent in CM-MSCs and CB-MSCs. Although osteogenic, chondrogenic, and neural differentiation was observed in MSCs from all sources, adipogenic differentiation was observed only in BM-MSCs. Conclusion: CM-MSCs are a dependable source of an unlimited number of MSCs for autologous and allogenic use in regenerative medicine. PMID:20376261

  2. Differential distributions of mononucleotide repeat sequences in 256 viral genomes and its potential implications.

    PubMed

    Qin, Lü; Ma, Yuxin; Liang, Pengbo; Tan, Zhongyang; Li, Shifang

    2014-07-10

    Mononucleotide repeats (MNRs) have been systematically investigated in the genomes of eukaryotic and prokaryotic organisms. However, detailed information on the distribution of MNRs in viral genomes is limited. In this study, we examined the distributions of MNRs in 256 fully sequenced virus genomes which showed extensive variations across viral genomes, and is significantly influenced by both genome size and CG content. Furthermore, the ratio of the observed to the expected number of MNRs (O/E ratio) appears to be influenced by both the host range and genome type of a particular virus. Additionally, the densities and frequencies of MNRs in genic regions are lower than in non-coding regions, suggesting that selective pressure acts on viral genomes. We also discuss the potential functional roles that these MNR loci could play in virus genomes. To our knowledge, this is the first analysis focusing on MNRs in viruses, and our study could have potential implications for a deeper understanding of virus genome stability and the co-evolution that occurs between a virus and its host. PMID:24786215

  3. Differential repair of potentially lethal damage in exponentially growing and quiescent 9L cells

    SciTech Connect

    Mendonca, M.S.; Rodriguez, A.; Alpen, E.L. (Lawrence Berkeley Laboratory, Berkeley (USA))

    1990-04-01

    The alteration of potentially lethal damage repair by postirradiation treatment with hypertonic saline (0.5 M PBS) was investigated in exponentially growing and quiescent 9L cells in vitro. A single dose of X rays (8.5 Gy) immediately followed by a 30-min treatment with hypertonic PBS at 37 degrees C reduced the survival of exponentially growing 9L cells by a factor of 13-18 compared to survival of irradiated immediately and delayed-plated cells, while the survival of quiescent cells was reduced by only a factor of 5-8. Survival curves confirmed the relative resistance of the quiescent 9L cells versus exponentially growing 9L cells to X rays plus hypertonic treatment. Both the slope and the shoulder of the survival curve were reduced to a greater extent in exponentially growing cells than in the quiescent cells by hypertonic treatment. The response of quiescent cells cannot be explained by either the duration of hypertonic treatment or the redistribution of the cells into G1 phase. We show that quiescent 9L cells can recover from hypertonically induced potentially lethal damage when incubated under conditions which have been found to delay progression through the cell cycle, and postulate that an altered chromatin structure or an enhanced repair capacity of quiescent 9L cells may be responsible for their resistance.

  4. Contribution of Vestibular-Evoked Myogenic Potential (VEMP) testing in the assessment and the differential diagnosis of otosclerosis

    PubMed Central

    Tramontani, Ourania; Gkoritsa, Eleni; Ferekidis, Eleftherios; Korres, Stavros G.

    2014-01-01

    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

  5. Potential outcome measures and trial design issues for multiple system atrophy.

    PubMed

    May, Susanne; Gilman, Sid; Sowell, B Brooke; Thomas, Ronald G; Stern, Matthew B; Colcher, Amy; Tanner, Caroline M; Huang, Neng; Novak, Peter; Reich, Stephen G; Jankovic, Joseph; Ondo, William G; Low, Phillip A; Sandroni, Paola; Lipp, Axel; Marshall, Frederick J; Wooten, Frederick; Shults, Clifford W

    2007-12-01

    Multiple system atrophy (MSA) is a neurodegenerative disorder exhibiting a combination of parkinsonism, cerebellar ataxia, and autonomic failure. A disease-specific scale, the Unified Multiple System Atrophy Rating Scale (UMSARS), has been developed and validated to measure progression of MSA, but its use as an outcome measure for therapeutic trials has not been evaluated. On the basis of twelve months of follow-up from an observational study of 67 patients with probable MSA, we evaluated three disease-specific scores: Activities of Daily Living, Motor Examination, and a combined score from the UMSARS and two general health scores, the Physical Health and Mental Health scores of the SF-36 health survey, for their use as outcome measures in a therapeutic trial. We discuss related design issues and provide sample size estimates. Scores based on the disease-specific UMSARS seemed to be equal or superior to scores based on the SF-36 health survey. They appeared to capture disease progression, were well correlated and required the smallest sample size. The UMSARS Motor Examination score exhibited the most favorable characteristics as an outcome measure for a therapeutic trial in MSA with 1 year of follow-up. PMID:17914727

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

    PubMed Central

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

    2014-01-01

    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

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

    PubMed

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

    2014-06-15

    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

  8. A Numerical Approach to Solving Nonlinear Differential Equations on a Grid with Potential Applicability to Computational Fluid Dynamics

    E-print Network

    Tveit, Jesper

    2014-01-01

    A finite element method for solving nonlinear differential equations on a grid, with potential applicability to computational fluid dynamics (CFD), is developed and tested. The current method facilitates the computation of solutions of a high polynomial degree on a grid. A high polynomial degree is achieved by interpolating both the value, and the value of the derivatives up to a given order, of continuously distributed unknown variables. The two-dimensional lid-driven cavity, a common benchmark problem for CFD methods, is used as a test case. It is shown that increasing the polynomial degree has some advantages, compared to increasing the number of grid-points, when solving the given benchmark problem using the current method. The current method yields results which agree well with previously published results for this test case.

  9. Exposure to potentially traumatic events in early childhood: differential links to emergent psychopathology

    PubMed Central

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

    2011-01-01

    Objective 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 violence and non-interpersonal events) and recent stressful life events were assessed with the Preschool Age Psychiatric Assessment (PAPA) and Child Life Events Scale. Child psychiatric symptoms and disorders were assessed with parent-reports in the PAPA, a comprehensive, developmentally sensitive interview. Sociodemographic risk, parental anxiety and depressive symptoms (Center for Epidemiologic Studies Depression, Beck Anxiety Inventory), and child developmental level (Mullen Scales of Early Learning) also were assessed. Results Violence exposure was broadly associated with psychiatric status in the areas of depression, separation anxiety, posttraumatic stress, and conduct problems, whereas potentially traumatic non-interpersonal exposure was associated with phobic anxiety. The majority of the associations between violence exposure and preschoolers’ symptoms were significant even when other key factors, including economic disadvantage and parental mood and anxiety symptoms, were controlled statistically. However, parental depressive/anxious symptoms may have partially or fully mediated the relationships between violence exposure and depressive and conduct symptoms. Conclusions Evidence of robust associations between violence exposure and early childhood internalizing and externalizing disorders and symptoms highlights the need for longitudinal prospective research concerning neurodevelopmental mechanisms and pathways. Findings underscore the relevance of assessing trauma exposure, particularly interpersonal violence, to identify young children at risk. PMID:20840502

  10. Differentiating anxiety and depression in children and adolescents: evidence from event-related brain potentials.

    PubMed

    Bress, Jennifer N; Meyer, Alexandria; Hajcak, Greg

    2015-01-01

    The current study, which was a reanalysis of previous data, focused on the error-related negativity (ERN)-an event-related potential (ERP) associated with error monitoring-and the feedback negativity (FN)-an ERP associated with reward processing. Two objectives motivated this study: first, to illustrate the relationship between the ERN and anxious symptoms, and the relationship between the FN and depressive symptoms; second, to explore whether the ERN and the FN relate uniquely to anxiety and depression, respectively, in children. EEG was collected from twenty-five 11- to 13-year-old participants (12 female; 23 Caucasian, 1 Asian, 1 of Caucasian and Hispanic ethnicity) during tasks designed to elicit an ERN and an FN. Participants and a parent completed questionnaires assessing the participant's anxious and depressive symptomatology. Increasing anxiety was related to a larger ERN, and increasing depression was related to a smaller FN. Further analysis demonstrated that these relationships remained significant when controlling for the contribution of other variables; that is, the ERN continued to predict anxiety when controlling for the FN and depression, and the FN continued to predict depression when controlling for the ERN and anxiety. Thus, in late childhood and early adolescence, the ERN and the FN appear to relate uniquely to anxious and depressive symptoms, respectively. Although this research is still in early stages, the ERN and the FN have the potential to inform trajectories of risk for anxiety and depression, and could be utilized in clinical settings as cost- and labor-efficient neural biomarkers. PMID:23879474

  11. Long-Term Potentiation Promotes Proliferation/Survival and Neuronal Differentiation of Neural Stem/Progenitor Cells

    PubMed Central

    Cho, Taesup; Ryu, Jae K.; Taghibiglou, Changiz; Ge, Yuan; Chan, Allen W.; Liu, Lidong; Lu, Jie; McLarnon, James G.; Wang, Yu Tian

    2013-01-01

    Neural stem cell (NSC) replacement therapy is considered a promising cell replacement therapy for various neurodegenerative diseases. However, the low rate of NSC survival and neurogenesis currently limits its clinical potential. Here, we examined if hippocampal long-term potentiation (LTP), one of the most well characterized forms of synaptic plasticity, promotes neurogenesis by facilitating proliferation/survival and neuronal differentiation of NSCs. We found that the induction of hippocampal LTP significantly facilitates proliferation/survival and neuronal differentiation of both endogenous neural progenitor cells (NPCs) and exogenously transplanted NSCs in the hippocampus in rats. These effects were eliminated by preventing LTP induction by pharmacological blockade of the N-methyl-D-aspartate glutamate receptor (NMDAR) via systemic application of the receptor antagonist, 3-[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid (CPP). Moreover, using a NPC-neuron co-culture system, we were able to demonstrate that the LTP-promoted NPC neurogenesis is at least in part mediated by a LTP-increased neuronal release of brain-derived neurotrophic factor (BDNF) and its consequent activation of tropomysosin receptor kinase B (TrkB) receptors on NSCs. Our results indicate that LTP promotes the neurogenesis of both endogenous and exogenously transplanted NSCs in the brain. The study suggests that pre-conditioning of the host brain receiving area with a LTP-inducing deep brain stimulation protocol prior to NSC transplantation may increase the likelihood of success of using NSC transplantation as an effective cell therapy for various neurodegenerative diseases. PMID:24146937

  12. Non-cell-autonomous microRNA165 acts in a dose-dependent manner to regulate multiple differentiation status in the Arabidopsis root.

    PubMed

    Miyashima, Shunsuke; Koi, Satoshi; Hashimoto, Takashi; Nakajima, Keiji

    2011-06-01

    In the development of multicellular organisms, cell fate is usually determined by exchanging positional information. Animals employ a class of intercellular signaling molecules that specify different cell fates by their dosage, but the existence of an equivalent system has not been demonstrated in plants, except that the growth regulator auxin has been proposed to act in a similar manner in certain developmental contexts. Recently, it has been reported that, in the Arabidopsis root meristem, endodermis-derived microRNA (miR) 165/166 non-cell-autonomously suppress the expression of the Class III HD-ZIP transcription factor PHABULOSA (PHB) in the peripheral stele, thereby specifying xylem differentiation. Here, we show that the miR165/166-dependent suppression of PHB is required not only for xylem specification, but also for differentiation of the pericycle, as well as for ground tissue patterning. Furthermore, using a plant system that allows quantitative control of miR165 production in the ground tissue, we show that endodermis-derived miR165 acts in a dose-dependent manner to form a graded distribution of PHB transcripts across the stele. These results reveal a previously unidentified role of miR165 in the differentiation of a broad range of root cell types and suggest that endodermis-derived miR165 acts in a dose-dependent manner to control multiple differentiation status in the Arabidopsis root. PMID:21558378

  13. The potential of using robotics in data acquisition from multiple sensors

    Microsoft Academic Search

    Rasmus N. Jřrgensen; Claus G. Sřrensen; Hans Jacobsen; Kristian Kirk; Hans Jřrgen Andersen; Del Nantt

    2005-01-01

    This paper shows the potential of using robotics for data acquisition within full-scale field trials. Robotics ensured simultaneously measurements from several sensors from GPS targeted sampling points. This was demonstrated by supporting a project developing methods to measure gap fraction and canopy structure in cereals. The project required measurements from ordinary barley canopy areas using a high- dynamic-range RGB camera,

  14. Expression profiling of the RPE in zebrafish smarca4 mutant revealed altered signals that potentially affect RPE and retinal differentiation

    PubMed Central

    Ma, Ping; Collery, Ross; Trowbridge, Sara; Zhong, Wenxuan; Leung, Yuk Fai

    2014-01-01

    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

  15. Preservation of Differentiation and Clonogenic Potential of Human Hematopoietic Stem and Progenitor Cells during Lyophilization and Ambient Storage

    PubMed Central

    Buchanan, Sandhya S.; Pyatt, David W.; Carpenter, John F.

    2010-01-01

    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

  16. A generalized Grubbs-Beck test statistic for detecting multiple potentially influential low outliers in flood series

    USGS Publications Warehouse

    Cohn, T.A.; England, J.F.; Berenbrock, C.E.; Mason, R.R.; Stedinger, J.R.; Lamontagne, J.R.

    2013-01-01

    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.

  17. Acrolein detection: potential theranostic utility in multiple sclerosis and spinal cord injury

    PubMed Central

    Tully, Melissa; Zheng, Lingxing; Shi, Riyi

    2015-01-01

    Oxidative stress has been implicated as a major pathological process underlying CNS disease and trauma. More specifically, acrolein, an unsaturated aldehyde, produced by way of lipid peroxidation, has been shown to play a crucial role in initiating and perpetuating detrimental effects associated with multiple sclerosis and spinal cord injury. In light of these findings, quantification of acrolein levels both systemically and locally could allow for the use of acrolein as a biomarker to aid in diagnosis and guide treatment regimens. The three main approaches currently available are acrolein derivatization followed byLC/GC–MS, application of an acrolein antibody and subsequent immunoblotting, and the 3-hydroxypropylmercapturic acid-based method. Of these three strategies, the 3-hydroxypropylmercapturic acid-based method is the least invasive allowing for rapid translation of acrolein detection into a clinical setting. PMID:24831349

  18. The potential role of B cell-targeted therapies in multiple sclerosis.

    PubMed

    Boster, Aaron; Ankeny, Daniel P; Racke, Michael K

    2010-12-24

    Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS. Until recently, most therapeutic interventions have targeted T cells in the treatment of MS. Recent data show that B cells also have a role in the pathogenesis of MS. The cerebrospinal fluid and CNS of MS patients contain B cells, plasma cells and immunoglobulins, and recent data indicate that B cells are involved in antigen presentation and T-cell activation, cytokine production, antibody secretion, demyelination and remyelination in MS. These advances in the understanding of B cells and their role in the pathophysiology of MS provide a strong rationale for B cell-targeted therapies. Recent clinical trials with rituximab highlight the possibility that B cells should be an important therapeutic target in patients with MS. PMID:21142258

  19. Proteomic Profiling in Multiple Sclerosis Clinical Courses Reveals Potential Biomarkers of Neurodegeneration

    PubMed Central

    Liguori, Maria; Qualtieri, Antonio; Tortorella, Carla; Direnzo, Vita; Bagalŕ, Angelo; Mastrapasqua, Mariangela; Spadafora, Patrizia; Trojano, Maria

    2014-01-01

    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

  20. Redox potential tuning through differential quinone binding in the photosynthetic reaction center of Rhodobacter sphaeroides.

    PubMed

    Vermaas, Josh V; Taguchi, Alexander T; Dikanov, Sergei A; Wraight, Colin A; Tajkhorshid, Emad

    2015-03-31

    Ubiquinone forms an integral part of the electron transport chain in cellular respiration and photosynthesis across a vast number of organisms. Prior experimental results have shown that the photosynthetic reaction center (RC) from Rhodobacter sphaeroides is only fully functional with a limited set of methoxy-bearing quinones, suggesting that specific interactions with this substituent are required to drive electron transport and the formation of quinol. The nature of these interactions has yet to be determined. Through parameterization of a CHARMM-compatible quinone force field and subsequent molecular dynamics simulations of the quinone-bound RC, we have investigated and characterized the interactions of the protein with the quinones in the Q(A) and Q(B) sites using both equilibrium simulation and thermodynamic integration. In particular, we identify a specific interaction between the 2-methoxy group of ubiquinone in the Q(B) site and the amide nitrogen of GlyL225 that we implicate in locking the orientation of the 2-methoxy group, thereby tuning the redox potential difference between the quinones occupying the Q(A) and Q(B) sites. Disruption of this interaction leads to weaker binding in a ubiquinone analogue that lacks a 2-methoxy group, a finding supported by reverse electron transfer electron paramagnetic resonance experiments of the Q(A)?Q(B)? biradical and competitive binding assays. PMID:25734689

  1. Differentially charged isoforms of apolipoprotein E from human blood are potential biomarkers of Alzheimer’s disease

    PubMed Central

    2014-01-01

    Introduction Alzheimer’s disease (AD) is the major cause of dementia among the elderly. Finding blood-based biomarkers for disease diagnosis and prognosis is urgently needed. Methods We studied protein distributions in brain tissues, cerebrospinal fluid (CSF), and blood of AD patients by using proteomics and a new proteomic method that we call “2D multiplexed Western blot” (2D mxWd). This method allows us to determine in multiple samples the electrophoretic patterns of protein isoforms with different isoelectric points. Results Apolipoprotein E (ApoE) displays a unique distribution of electrophoretic isoforms in the presence of AD and also a unique pattern specific to the APOE genotype. Conclusions The isoelectric distribution of differentially charged ApoE isoforms was used to determine the presence of AD in a small group of samples. Further studies are needed to validate their use as predictors of disease onset and progression, and as biomarkers for determining the efficacy of therapeutic treatments. PMID:25478016

  2. Electronic and transport properties of T-graphene nanoribbon: Symmetry-dependent multiple Dirac points, negative differential resistance and linear current-bias characteristics

    NASA Astrophysics Data System (ADS)

    Dai, C. J.; Yan, X. H.; Xiao, Y.; Guo, Y. D.

    2014-08-01

    Based on the tight-binding method and density functional theory, band structures and transport properties of T-graphene nanoribbons are investigated. By constructing and solving the tight-binding Hamiltonian, we derived the analytic expressions of the linear dispersion relation and Fermi velocity of Dirac-like fermions for armchair T-graphene nanoribbons. Multiple Dirac points, which are triggered by the mirror symmetry of armchair T-graphene nanoribbons, are observed. The number and positions of multiple Dirac points can be well explained by our analytic expressions. Tight-binding results are confirmed by the results from density functional calculations. Moreover, armchair T-graphene nanoribbons exhibit negative differential resistance, whereas zigzag T-graphene nanoribbons have linear current-bias voltage characteristics near the Fermi level.

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

    SciTech Connect

    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

    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.

  4. Deregulation of PAX2 expression in renal cell tumours: mechanisms and potential use in differential diagnosis

    PubMed Central

    Patrício, Patrícia; Ramalho-Carvalho, Joăo; Costa-Pinheiro, Pedro; Almeida, Mafalda; Barros-Silva, Joăo Diogo; Vieira, Joana; Dias, Paula Cristina; Lobo, Francisco; Oliveira, Jorge; Teixeira, Manuel R; Henrique, Rui; Jeronimo, Carmen

    2013-01-01

    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

  5. Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders.

    PubMed

    Campos, Alline Cristina; Moreira, Fabricio Araújo; Gomes, Felipe Villela; Del Bel, Elaine Aparecida; Guimarăes, Francisco Silveira

    2012-12-01

    Cannabidiol (CBD) is a major phytocannabinoid present in the Cannabis sativa plant. It lacks the psychotomimetic and other psychotropic effects that the main plant compound ?(9)-tetrahydrocannabinol (THC) being able, on the contrary, to antagonize these effects. This property, together with its safety profile, was an initial stimulus for the investigation of CBD pharmacological properties. It is now clear that CBD has therapeutic potential over a wide range of non-psychiatric and psychiatric disorders such as anxiety, depression and psychosis. Although the pharmacological effects of CBD in different biological systems have been extensively investigated by in vitro studies, the mechanisms responsible for its therapeutic potential are still not clear. Here, we review recent in vivo studies indicating that these mechanisms are not unitary but rather depend on the behavioural response being measured. Acute anxiolytic and antidepressant-like effects seem to rely mainly on facilitation of 5-HT1A-mediated neurotransmission in key brain areas related to defensive responses, including the dorsal periaqueductal grey, bed nucleus of the stria terminalis and medial prefrontal cortex. Other effects, such as anti-compulsive, increased extinction and impaired reconsolidation of aversive memories, and facilitation of adult hippocampal neurogenesis could depend on potentiation of anandamide-mediated neurotransmission. Finally, activation of TRPV1 channels may help us to explain the antipsychotic effect and the bell-shaped dose-response curves commonly observed with CBD. Considering its safety profile and wide range of therapeutic potential, however, further studies are needed to investigate the involvement of other possible mechanisms (e.g. inhibition of adenosine uptake, inverse agonism at CB2 receptor, CB1 receptor antagonism, GPR55 antagonism, PPAR? receptors agonism, intracellular (Ca(2+)) increase, etc.), on CBD behavioural effects. PMID:23108553

  6. Matched filtering and multiple-hypothesis tracking applied to C-fiber action potentials recorded in human nerves

    NASA Astrophysics Data System (ADS)

    Hansson, Bjorn; Forster, Clemens; Torebjork, Erik

    1998-09-01

    We describe an application of multiple target tracking (MTT) to microneurography, with the purpose of estimating conduction velocity changes and recovery constants of human nerve C-fibers. In this paper, the focus is on the detection and the tracking of the nerve action potentials (APs). The subsequent parameter estimation is described only briefly. Results from an application of the tracking system on real data recorded inhuman subjects are presented. Action potentials form C-fibers were recorded with a thin needle electrode inserted into the peroneal nerve of awake human subjects. The APs were detected by a matched filter constituting a maximum likelihood constant false alarm rate detector. By utilizing the multiple hypothesis tracking method, the detected APs in each trace were associated to individual nerve fibers by their typical conduction latencies in response to electrical stimulation in the skin. The measurements were 1D, and the APs were spaced in time with intersecting, piecewise continuous, trajectories. The amplitude of the APs was varying slowly over time for each C-fiber and was in general different for different fibers. It was therefore incorporated into the tracking algorithm to improve its performance.

  7. Serum Parathyroid Hormone Is a New Potential Risk Factor in Multiple Myeloma

    PubMed Central

    Won, Eun-Jeong; Kim, Hye-Ran; Choi, Hyun-Jung; Park, Hye-Ri; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook; Shin, Myung-Geun

    2014-01-01

    We hypothesized that serum PTH might be associated with various clinicopathological parameters in multiple myeloma (MM). So we investigated the implications of serum PTH in MM patients and the relationship with other risk factors of MM. A total of 115 patients who were newly diagnosed with MM were enrolled. Serum PTH level was 24.7 ± 34.9 (ranged 0.0–284.1)?pg/mL. Serum levels of IgG, IgM, FLC-lambda, albumin, and LDH were in positive correlation with serum PTH. Compared to non-high PTH (<68.3?pg/mL) group, the hazard ratio (HR) for overall survival was higher for group with high PTH level (?68.3?pg/mL) (HR, 1.710). Furthermore, the patient group with high PTH level showed inferior progression-free survival than non-high PTH group (P = 0.056). Interestingly, subgroup analysis showed that serum PTH level at diagnosis was associated with risk factors and clinical outcome in MM patients, especially in complete remission group, transplantation cases, ISS stage II cases, and cases without chromosome abnormality. In conclusion, this study showed that blood PTH level in MM at diagnosis was associated with risk factors and clinical outcome in MM patients. PMID:24967406

  8. Is T-bet a potential therapeutic target in multiple sclerosis?

    PubMed

    Racke, Michael K; Yang, Yuhong; Lovett-Racke, Amy E

    2014-08-01

    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

  9. Differential contribution of BDNF and NGF to long-term potentiation in the superior cervical ganglion of the rat.

    PubMed

    Arias, Erwin R; Valle-Leija, Pablo; Morales, Miguel A; Cifuentes, Fredy

    2014-06-01

    Synaptic transmission in the sympathetic nervous system is a plastic process modulated by different factors. We characterized the effects of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) on basal transmission and ganglionic long-term potentiation (LTP) in the rat superior cervical ganglion. LTP was elicited by supramaximal tetanic stimulation (40 Hz, 3 s) of the sympathetic trunk and was quantified by measuring LTP decay time and LTP extent. Neurotrophins did not affect basal transmission, however, they differentially affected LTP. BDNF (200 ng/ml) increased LTP decay time and LTP extent 2.0-fold (p < 0.01). In contrast, NGF showed a dual effect: 200 ng/ml NGF reduced LTP decay time and LTP extent to 53% and to 32% of control value (p < 0.0001 and p < 0.02; respectively), whereas >350 ng/ml NGF significantly increased LTP decay time and LTP extent (p < 0.02). Digital analysis of compound action potentials suggests that neurotrophins could change the synchronization of unitary action potentials. Pharmacological data obtained in intact ganglia show that C2-ceramide produced a 2-fold enhancement in LTP, whereas tyrphostin AG879, an inhibitor of tyrosine kinase activity, reversed the NGF blockade and produced by itself an enhancement in LTP. In sliced ganglia we observed that an anti-TrkA antibody reversed the NGF-induced LTP blockade. Immunohistochemistry studies revealed that 83% of ganglionic neurons express TrkA, whereas 52% express p75 receptor, and 18% express TrkB receptor. We propose that p75 neurotrophin receptors and probably TrkB signaling enhance LTP, whereas TrkA signaling reduces it. PMID:24530966

  10. Differential metabolomic analysis of the potential antiproliferative mechanism of olive leaf extract on the JIMT-1 breast cancer cell line.

    PubMed

    Barrajón-Catalán, Enrique; Taamalli, Amani; Quirantes-Piné, Rosa; Roldan-Segura, Cristina; Arráez-Román, David; Segura-Carretero, Antonio; Micol, Vicente; Zarrouk, Mokhtar

    2015-02-01

    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

  11. Immunohistochemical expression of SALL4 in hepatocellular carcinoma, a potential pitfall in the differential diagnosis of yolk sac tumors.

    PubMed

    Gonzalez-Roibon, Nilda; Katz, Betina; Chaux, Alcides; Sharma, Rajni; Munari, Enrico; Faraj, Sheila F; Illei, Peter B; Torbenson, Michael; Netto, George J

    2013-07-01

    SALL4 is a transcription factor that serves as a marker of yolk sac tumor. Yolk sac tumor and hepatocellular carcinoma share histologic, serologic, and immunohistochemical features. Previous studies have shown lack of SALL4 expression in hepatocellular carcinoma, suggesting utility in this differential diagnosis. Sixty-nine samples of hepatocellular carcinoma were retrieved from surgical pathology archives and used to construct 9 tissue microarrays. A germ cell tumor tissue microarray containing 10 yolk sac tumors was used for comparison. Extent, intensity, and pattern of nuclear SALL4 expression were assessed in each spot. Mean percentage of expression was calculated for each tumor and used during analysis. Optimal discriminatory extent of expression cutoff was determined by receiver operating characteristic curve analysis. Other potential discriminatory markers including Hep Par1 were also evaluated. Forty-six percent (32/69) of hepatocellular carcinoma and all yolk sac tumors revealed at least focal expression of SALL4. A unique punctuate/clumped pattern of nuclear staining was present in 94% (30/32) of hepatocellular carcinoma, whereas all yolk sac tumors displayed a diffuse finely granular nuclear staining pattern. A 25% extent of SALL4 expression cutoff was found to be optimal for the distinction of yolk sac tumor from hepatocellular carcinoma yielding a sensitivity of 100%, specificity of 92.8%, and a positive predictive value of 66.6% for yolk sac tumor diagnosis. The addition of Hep Par1 increased the specificity (99%) and positive predictive value (90%). This is the first report of SALL4 expression in hepatocellular carcinoma. Our finding should be taken into consideration in the differential diagnosis of hepatocellular carcinoma and yolk sac tumor. The unique punctuate/clumped pattern seen in hepatocellular carcinoma cases could be of further discriminatory value. PMID:23347651

  12. Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis

    PubMed Central

    Darlington, Peter J; Boivin, Marie-Noëlle; Bar-Or, Amit

    2011-01-01

    Phase I clinical trials exploring the use of autologous mesenchymal stem cell (MSC) therapy for the treatment of multiple sclerosis (MS) have begun in a number of centers across the world. MS is a complex and chronic immune-mediated and neurodegenerative disease influenced by genetic susceptibility and environmental risk factors. The ideal treatment for MS would involve both attenuation of detrimental inflammatory responses, and induction of a degree of tissue protection/regeneration within the CNS. Preclinical studies have demonstrated that both human-derived and murine-derived MSCs are able to improve outcomes in the animal model of MS, experimental autoimmune encephalomyelitis. How MSCs ameliorate experimental autoimmune encephalomyelitis is being intensely investigated. One of the major mechanisms of action of MSC therapy is to inhibit various components of the immune system that contribute to tissue destruction. Emerging evidence now supports the idea that MSCs can access the CNS where they can provide protection against tissue damage, and may facilitate tissue regeneration through the production of growth factors. The prospect of cell-based therapy using MSCs has several advantages, including the relative ease with which they can be extracted from autologous bone marrow or adipose tissue and expanded in vitro to reach the purity and numbers required for transplantation, and the fact that MSC therapy has already been used in other human disease settings, such as graft-versus-host and cardiac disease, with initial reports indicating a good safety profile. This article will focus on the theoretical and practical issues relevant to considerations of MSC therapy in the context of MS. PMID:21864075

  13. Epstein–Barr virus and multiple sclerosis: potential opportunities for immunotherapy

    PubMed Central

    Pender, Michael P; Burrows, Scott R

    2014-01-01

    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

  14. Differential Expression of Adenine Nucleotide Converting Enzymes in Mitochondrial Intermembrane Space: A Potential Role of Adenylate Kinase Isozyme 2 in Neutrophil Differentiation

    PubMed Central

    Tanimura, Ayako; Horiguchi, Taigo; Miyoshi, Keiko; Hagita, Hiroko; Noma, Takafumi

    2014-01-01

    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

  15. Aspirin and multiple sclerosis.

    PubMed

    Tsau, Sheila; Emerson, Mitchell R; Lynch, Sharon G; LeVine, Steven M

    2015-01-01

    Aspirin is widely used to lessen the risks of cardiovascular events. Some studies suggest that patients with multiple sclerosis have an increased risk for some cardiovascular events, for example, venous thromboembolism and perhaps ischemic strokes, raising the possibility that aspirin could lessen these increased risks in this population or subgroups (patients with limited mobility and/or antiphospholipid antibodies). However, aspirin causes a small increased risk of hemorrhagic stroke, which is a concern as it could potentially worsen a compromised blood-brain barrier. Aspirin has the potential to ameliorate the disease process in multiple sclerosis (for example, by limiting some components of inflammation), but aspirin also has the potential to inhibit mitochondrial complex I activity, which is already reduced in multiple sclerosis. In an experimental setting of a cerebral ischemic lesion, aspirin promoted the proliferation and/or differentiation of oligodendrocyte precursors, raising the possibility that aspirin could facilitate remyelination efforts in multiple sclerosis. Other actions by aspirin may lead to small improvements of some symptoms (for example, lessening fatigue). Here we consider potential benefits and risks of aspirin usage by patients with multiple sclerosis. PMID:26123634

  16. A PATH INTEGRAL METHOD FOR COARSE-GRAINING NOISE IN STOCHASTIC DIFFERENTIAL EQUATIONS WITH MULTIPLE TIME SCALES

    Microsoft Academic Search

    TOBIAS SCH; RICHARD O. MOOREy

    We present a new path integral method to analyze stochastically perturbed ordinary dierential equations with multiple time scales. The objective of this method is to derive from the original system a new stochastic dierential equation describing the system's evolution on slow time scales. For this purpose, we start from the corresponding path integral representation of the stochastic system and apply

  17. Differential Vocational Rehabilitation Service Patterns Related to the Job Retention and Job-Seeking Needs of Individuals with Multiple Sclerosis

    ERIC Educational Resources Information Center

    Tansey, Timothy N.; Strauser, David; Frain, Michael P.; Bishop, Malachy; Chiu, Chung-Yi; Kaya, Cahit; Chan, Fong

    2015-01-01

    The experience of living with multiple sclerosis (MS) can have a profound effect on employment. The impact of MS is a complex interaction of personal, medical, functional, financial, and psychosocial variables that ultimately results in up to 80% of persons with MS leaving their jobs within 10 years of their diagnosis. The aim of this study was to…

  18. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma

    PubMed Central

    Fulciniti, Mariateresa; Tassone, Pierfrancesco; Hideshima, Teru; Vallet, Sonia; Nanjappa, Puru; Ettenberg, Seth A.; Shen, Zhenxin; Patel, Nipun; Tai, Yu-tzu; Chauhan, Dharminder; Mitsiades, Constantine; Prabhala, Rao; Raje, Noopur; Anderson, Kenneth C.; Stover, David R.

    2009-01-01

    Decreased activity of osteoblasts (OBs) contributes to osteolytic lesions in multiple myeloma (MM). The production of the soluble Wnt inhibitor Dickkopf-1 (DKK1) by MM cells inhibits OB activity, and its serum level correlates with focal bone lesions in MM. Therefore, we have evaluated bone anabolic effects of a DKK1 neutralizing antibody (BHQ880) in MM. In vitro BHQ880 increased OB differentiation, neutralized the negative effect of MM cells on osteoblastogenesis, and reduced IL-6 secretion. In a severe combined immunodeficiency (SCID)–hu murine model of human MM, BHQ880 treatment led to a significant increase in OB number, serum human osteocalcin level, and trabecular bone. Although BHQ880 had no direct effect on MM cell growth, it significantly inhibited growth of MM cells in the presence of bone marrow stromal cells (BMSCs) in vitro. This effect was associated with inhibition of BMSC/MM cell adhesion and production of IL-6. In addition, BHQ880 up-regulated ?-catenin level while down-regulating nuclear factor-?B (NF-?B) activity in BMSC. Interestingly, we also observed in vivo inhibition of MM cell growth by BHQ880 treatment in the SCID-hu murine model. These results confirm DKK1 as an important therapeutic target in myeloma and provide the rationale for clinical evaluation of BHQ880 to improve bone disease and to inhibit MM growth. PMID:19417213

  19. Anti-DKK1 mAb (BHQ880) as a potential therapeutic agent for multiple myeloma.

    PubMed

    Fulciniti, Mariateresa; Tassone, Pierfrancesco; Hideshima, Teru; Vallet, Sonia; Nanjappa, Puru; Ettenberg, Seth A; Shen, Zhenxin; Patel, Nipun; Tai, Yu-Tzu; Chauhan, Dharminder; Mitsiades, Constantine; Prabhala, Rao; Raje, Noopur; Anderson, Kenneth C; Stover, David R; Munshi, Nikhil C

    2009-07-01

    Decreased activity of osteoblasts (OBs) contributes to osteolytic lesions in multiple myeloma (MM). The production of the soluble Wnt inhibitor Dickkopf-1 (DKK1) by MM cells inhibits OB activity, and its serum level correlates with focal bone lesions in MM. Therefore, we have evaluated bone anabolic effects of a DKK1 neutralizing antibody (BHQ880) in MM. In vitro BHQ880 increased OB differentiation, neutralized the negative effect of MM cells on osteoblastogenesis, and reduced IL-6 secretion. In a severe combined immunodeficiency (SCID)-hu murine model of human MM, BHQ880 treatment led to a significant increase in OB number, serum human osteocalcin level, and trabecular bone. Although BHQ880 had no direct effect on MM cell growth, it significantly inhibited growth of MM cells in the presence of bone marrow stromal cells (BMSCs) in vitro. This effect was associated with inhibition of BMSC/MM cell adhesion and production of IL-6. In addition, BHQ880 up-regulated beta-catenin level while down-regulating nuclear factor-kappaB (NF-kappaB) activity in BMSC. Interestingly, we also observed in vivo inhibition of MM cell growth by BHQ880 treatment in the SCID-hu murine model. These results confirm DKK1 as an important therapeutic target in myeloma and provide the rationale for clinical evaluation of BHQ880 to improve bone disease and to inhibit MM growth. PMID:19417213

  20. Gene expression profiling and real-time PCR analyses identify novel potential cancer-testis antigens in multiple myeloma

    PubMed Central

    Condomines, Maud; Hose, Dirk; Rčme, Thierry; Requirand, Guilhem; Hundemer, Michael; Schoenhals, Matthieu; Goldschmidt, Hartmut; Klein, Bernard

    2009-01-01

    Cancer-testis (CT) antigens are attractive targets for immunotherapeutic strategies since they are aberrantly expressed in malignant cells and not, or in limited number, in somatic tissues, except germ cells. To identify novel CT genes in multiple myeloma, we used Affymetrix HG-U133 gene expression profiles of 5 testis, 64 primary myeloma cell (MMC) and 24 normal tissue (NT) samples. A 5-filter method was developed to keep known CT genes while deleting non-CT genes. Starting from 44928 probe sets, including probe sets for 18 previously-described CT genes, we have obtained 82 genes expressed in MMC and testis and not detected in more than 6 NT. This list includes 14 of the 18 known CT genes and 68 novel putative CT genes. Real-time RT-PCR was performed for 34 genes in 12 NT, 5 MMC samples and one sample of 5 pooled testes. It has validated the CT status of 23/34 genes (67%). We found one novel “testis-restricted” gene (expression in testis and tumor only) – TEX14 –, 8 “tissue-restricted” (mRNA detected in 1 or 2 non-gametogenic tissues), and 7 “differentially expressed” (mRNA detected in three to six non-gametogenic tissues) CT genes. Further studies are warranted to determine the immunogenicity of these novel CT antigen candidates. PMID:19542363

  1. An Empirical Bayes Adjustment to Multiple p-values For the Detection of Differentially Expressed Genes in Microarray Experiments

    Microsoft Academic Search

    Somnath Datta; Susmita Datta

    2000-01-01

    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

  2. Modeling the Potential Effects of New Tobacco Products and Policies: A Dynamic Population Model for Multiple Product Use and Harm

    PubMed Central

    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

    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

  3. Carboxyl-terminal domain of transient receptor potential vanilloid 1 contains distinct segments differentially involved in capsaicin- and heat-induced desensitization.

    PubMed

    Joseph, John; Wang, Sen; Lee, Jongseok; Ro, Jin Y; Chung, Man-Kyo

    2013-12-13

    Multiple Ca(2+)-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 Ca(2+), 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 Lys(155), 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

  4. Humin as an electron donor for enhancement of multiple microbial reduction reactions with different redox potentials in a consortium.

    PubMed

    Zhang, Dongdong; Zhang, Chunfang; Xiao, Zhixing; Suzuki, Daisuke; Katayama, Arata

    2015-02-01

    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

  5. Potential of two-dimensional electro-fluid-dynamic devices for continuous purification of multiple components from complex samples.

    PubMed

    Liu, Chang; Luo, Yong; Maxwell, E Jane; Fang, Ning; Chen, David D Y

    2011-11-01

    Two-dimensional electro-fluid-dynamic (EFD) devices, in which both electric field and hydrodynamic pressure are used to drive the analyte and fluid migration, enable two-dimensional channel networks to be used for chemical separation instead of one-dimensional column separation systems. Investigation of the theory of mass transfer in symmetrical Y-shaped EFD devices shows that the magnitude of pressure-induced velocity in lateral channels at critical boundary conditions between different steady state migration paths is independent of the channel cross-sectional area ratio. Therefore, the analyte has four possible mass transfer pathways according to the electric field and pressure setup in all symmetrical Y-shaped 2-D EFD devices, and such devices with any cross-sectional area ratio have the capacity to continuously purify two analytes from a mixture simultaneously. In addition, a new format of multiple-branched 2-D EFD devices is introduced to process multiple analytes. A "proof-reading" mechanism based on the infinite resolution conditions ensures the purity of the components collected. The separation processes are simulated by COMSOL Multiphysics, and the migration behavior of the analytes was monitored using fluorescent dyes to verify the flow behavior of different analytes in individual channels. These 2-D EFD devices offer the potential of continuous fractionation and purification of analytes from complex sample mixtures. PMID:21923103

  6. Differential and Common Leukemogenic Potentials of Multiple NUP98-Hox Fusion Proteins Alone or with Meis1

    Microsoft Academic Search

    Nicolas Pineault; Carolina Abramovich; Hideaki Ohta; R. Keith Humphries

    2004-01-01

    NUP98-Hox fusion genes are newly identified oncogenes isolated in myeloid leukemias. Intriguingly, only Abd-B Hox genes have been reported as fusion partners, indicating that they may have unique overlapping leukemogenic properties. To address this hypothesis, we engineered novel NUP98 fusions with Hox genes not previously identified as fusion partners: the Abd-B-like gene HOXA10 and two Antennepedia-like genes, HOXB3 and HOXB4.

  7. Proteases Potentiate Fibrocyte Differentiation 

    E-print Network

    Galvis Carvajal, Elkin David

    2013-09-27

    45% of deaths in the United States involve fibrosing diseases and the treatment of non-healing chronic wounds costs more than $25 billion annually in the United States alone. Scar tissue formation plays a critical role in both wound healing...

  8. Population Differentiation and Species Formation in the Deep Sea: The Potential Role of Environmental Gradients and Depth

    PubMed Central

    Jennings, Robert M.; Etter, Ron J.; Ficarra, Lynn

    2013-01-01

    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

  9. Recombinant human bone morphogenetic protein 2B stimulates PC12 cell differentiation: potentiation and binding to type IV collagen

    PubMed Central

    1992-01-01

    Bone morphogenetic protein 2B (BMP 2B, also known as BMP 4) induces cartilage and bone morphogenesis in ectopic extraskeletal sites. BMP 2B is one of several bone morphogenetic proteins which along with activins and inhibins are members of the transforming growth factor-beta (TGF- beta) family. Both BMP 2B and activin A, but not TGF-beta 1, induce rat pheochromocytoma PC12 neuronal cell differentiation and expression of VGF, a nervous system-specific mRNA. PC12 cells exhibited approximately 2,500 receptors per cell for BMP 2B with an apparent dissociation constant of 19 pM. Extracellular matrix components, including fibronectin, laminin, and collagen type IV potentiated the activity of BMP and activin A, with the latter being the most active. Direct experiments demonstrated that radioiodinated BMP 2B bound to collagen type IV better than to either laminin or fibronectin. These data demonstrate a common neurotrophic activity of both BMP 2B and activin A, and suggest that these regulatory molecules alone and in conjunction with extracellular matrix components may play a role in both the development and repair of nervous tissue. PMID:1469059

  10. Differential sensitivity of osteoblasts and bacterial pathogens to 405-nm light highlighting potential for decontamination applications in orthopedic surgery

    NASA Astrophysics Data System (ADS)

    Ramakrishnan, Praveen; Maclean, Michelle; MacGregor, Scott J.; Anderson, John G.; Grant, M. Helen

    2014-10-01

    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.

  11. Microbial Monitoring of Pathogens by Comparing Multiple Real-Time PCR Platforms for Potential Space Applications

    NASA Technical Reports Server (NTRS)

    Birmele, Michele

    2012-01-01

    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.

  12. Gas and Gas Hydrate Potential Offshore Amasra,Bartin and Zonguldak and Possible Agent for Multiple BSR Occurrence

    NASA Astrophysics Data System (ADS)

    Mert Küçük, Hilmi; Dondurur, Derman; Özel, Özkan; S?nayuç, Ça?lar; Merey, ?ükrü; Parlaktuna, Mahmut; Çifçi, Günay

    2015-04-01

    Gas hydrates, shallow gases and mud volcanoes have been studied intensively in the Black Sea in recent years. Researches have shown that the Black Sea region has an important potential about hydrocarbon. BSR reflections in the seismic sections and seabed sampling studies also have proven the formations of hydrates clearly. In this respect, total of 2400 km multichannel seismic reflection, chirp and multibeam bathymetry data were collected along shelf to abyssal plain in 2010 and 2012 offshore Amasra, Bart?n, Zonguldak-Kozlu in the central Black Sea.. Collected data represent BSRs, bright spots and transparent zones. It has been clearly observed that possible gas chimneys cross the base of gas hydrate stability zones as a result of possible weak zones in the gas hydrate bearing sediments. Seabed samples were collected closely to possible gas chimneys due to shallow gas anomalies in the data. Head space gas cromatography was applied to seabed samples to observe gas composition and the gas cromatography results represented hydrocarbon gases such as Methane, Ethane, Propane, i-Butane, n-Butane, i-Pentane, n-Pentane and Hexane. Thermogenic gas production by Turkish Petroleum Corp. from Akçakoca-1 and Ayazl?-1 well is just located at the southwest of the study area and the observations of the study area point out there is also thermogenic gas potential at the eastern side of the Akçakoca. In addition, multiple-BSRs were observed in the study area and it is thought the key point of the multiple-BSRs are different gas compositions. This suggests that hydrate formations can be formed by gas mixtures. Changing of the thermobaric conditions can trigger dissociation of the gas hydrates in the marine sediments due to sedimentary load and changing of the water temperature around seabed. Our gas hydrate modelling study suggest that gas hydrates are behaving while their dissociation process if the gas hydrates are generated by gas mixture. Monitoring of our gas hydrate modelling study based on depressurization at constant temperature have shown that some of the gases start to dissociate while the other gases are stable in the gas hydrate formation. This respective dissociation of the gases from gas hydrates suggest that each multiple-BSR can be related with hydrate formations including different gas composition.

  13. Neural Precursors Derived from Embryonic Stem Cells, but Not Those from Fetal Ventral Mesencephalon, Maintain the Potential to Differentiate into Dopaminergic Neurons After Expansion In Vitro

    Microsoft Academic Search

    Sangmi Chung; Byoung-Soo Shin; Michelle Hwang; Thomas Lardaro; Un Jung Kang; Ole Isacson; Kwang-Soo Kim

    2006-01-01

    Neural precursors (NPs) derived from ventral mesencepha- lon (VM) normally generate dopaminergic (DA) neurons in vivo but lose their potential to differentiate into DA neurons during mitogenic expansion in vitro, hampering their effi- cient use as a transplantable and experimental cell source. Because embryonic stem (ES) cell-derived NPs (ES NP) do not go through the same maturation process during in

  14. Brain stem auditory evoked potentials in patients with multiple system atrophy with progressive autonomic failure (Shy-Drager syndrome).

    PubMed Central

    Prasher, D; Bannister, R

    1986-01-01

    Brain stem potentials from three groups of patients, namely those with pure progressive autonomic failure, Parkinson's disease and multisystem atrophy with progressive autonomic failure (Shy-Drager syndrome) were compared with each other and a group of normal subjects. In virtually all the patients with multisystem atrophy with progressive autonomic failure the brain stem potentials were abnormal in contrast to normal findings with Parkinson's disease. The closely associated group of patients with progressive autonomic failure alone also revealed no abnormalities of the BAEP. This separation of the two groups, Parkinson's disease and progressive autonomic failure from multisystem atrophy with progressive autonomic failure is important clinically as multiple system atrophy of the Shy-Drager type has extra-pyramidal features closely resembling Parkinsonism or a late onset cerebellar degeneration. From the abnormalities of the brain stem response in multisystem atrophy with progressive autonomic failure, it is clear that some disruption of the auditory pathway occurs in the ponto-medullary region as in nearly all patients there is a significant delay or reduction in the amplitude of components of the response generated beyond this region. The most likely area involved is the superior olivary complex. Images PMID:3958741

  15. Metformin Inhibits Monocyte-to-Macrophage Differentiation via AMPK-Mediated Inhibition of STAT3 Activation: Potential Role in Atherosclerosis.

    PubMed

    Vasamsetti, Sathish Babu; Karnewar, Santosh; Kanugula, Anantha Koteswararao; Thatipalli, Avinash Raj; Kumar, Jerald Mahesh; Kotamraju, Srigiridhar

    2015-06-01

    Monocyte-to-macrophage differentiation is a critical event that accentuates atherosclerosis by promoting an inflammatory environment within the vessel wall. In this study, we investigated the molecular mechanisms responsible for monocyte-to-macrophage differentiation and, subsequently, the effect of metformin in regressing angiotensin II (Ang-II)-mediated atheromatous plaque formation in ApoE(-/-) mice. AMPK activity was dose and time dependently downregulated during phorbol myristate acetate (PMA)-induced monocyte-to-macrophage differentiation, which was accompanied by an upregulation of proinflammatory cytokine production. Of note, AMPK activators metformin and AICAR significantly attenuated PMA-induced monocyte-to-macrophage differentiation and proinflammatory cytokine production. However, inhibition of AMPK activity alone by compound C was ineffective in promoting monocyte-to-macrophage differentiation in the absence of PMA. On the other hand, inhibition of c-Jun N-terminal kinase activity inhibited PMA-induced inflammation but not differentiation, suggesting that inflammation and differentiation are independent events. In contrast, inhibition of STAT3 activity inhibited both inflammation and monocyte-to-macrophage differentiation. By decreasing STAT3 phosphorylation, metformin and AICAR through increased AMPK activation caused inhibition of monocyte-to-macrophage differentiation. Metformin attenuated Ang-II-induced atheromatous plaque formation and aortic aneurysm in ApoE(-/-) mice partly by reducing monocyte infiltration. We conclude that the AMPK-STAT3 axis plays a pivotal role in regulating monocyte-to-macrophage differentiation and that by decreasing STAT3 phosphorylation through increased AMPK activity, AMPK activators inhibit monocyte-to-macrophage differentiation. PMID:25552600

  16. Determination of. alpha. sub s from a differential-jet-multiplicity distribution in e sup + e sup minus collisions at radical s =29 and 91 GeV

    SciTech Connect

    Komamiya, S.; Le Diberder, F.; Abrams, G.S.; Adolphsen, C.E.; Averill, D.; Ballam, J.; Barish, B.C.; Barklow, T.; Barnett, B.A.; Bartelt, J.; Bethke, S.; Blockus, D.; Bonvicini, G.; Boyarski, A.; Brabson, B.; Breakstone, A.; Bulos, F.; Burchat, P.R.; Burke, D.L.; Cence, R.J.; Chapman, J.; Chmeissani, M.; Cords, D.; Coupal, D.P.; Dauncey, P.; DeStaebler, H.C.; Dorfan, D.E.; Dorfan, J.M.; Drewer, D.C.; Elia, R.; Feldman, G.J.; Fernandes, D.; Field, R.C.; Ford, W.T.; Fordham, C.; Frey, R.; Fujino, D.; Gan, K.K.; Gatto, C.; Gero, E.; Gidal, G.; Glanzman, T.; Goldhaber, G.; Gomez Cadenas, J.J.; Gratta, G.; Grindhammer, G.; Grosse-Wiesmann, P.; Hanson, G.; Harr, R.; Harral, B.; Harris, F.A.; Hawkes, C.M.; Hayes, K.; Hearty, C.; Heusch, C.A.; Hildreth, M.D.; Himel, T.; Hinshaw, D.A.; Hong, S.J.; Hutchinson, D.; Hylen, J.; Innes, W.R.; Jacobsen, R.G.; Jaros, J.A.; Jung, C.K.; Kadyk, J.A.; Kent, J.; King, M.; Klein, S.R.; Koetke, D.S.; Koska, W.; Kowalski, L.A.; Kozanecki, W.; Kral, J.F.; Kuhle

    1990-02-26

    We measured the differential jet-multiplicity distribution in {ital e}{sup +}{ital e}{sup {minus}} annihilation with the Mark II detector. This distribution is compared with the second-order QCD prediction and {alpha}{sub {ital s}} is determined to be 0.123{plus minus}0.009{plus minus}0.005 at {radical}{ital s}{approx}{ital M}{sub {ital Z}} (at the SLAC Linear Collider) and 0.149{plus minus}0.002{plus minus}0.007 at {radical}{ital s}=29 GeV (at the SLAC storage ring PEP). The running of {alpha}{sub {ital s}} between these two center-of-mass energies is consistent with the QCD prediction.

  17. 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

    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

    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 %.

  18. Dimethyloxaloylglycine Increases the Bone Healing Capacity of Adipose-Derived Stem Cells by Promoting Osteogenic Differentiation and Angiogenic Potential

    PubMed Central

    Ding, Hao; Gao, You-Shui; Wang, Yang; Hu, Chen

    2014-01-01

    Hypoxia inducible factor-1? (HIF-1?) plays an important role in angiogenesis-osteogenesis coupling during bone regeneration, which can enhance the bone healing capacity of mesenchymal stem cells (MSCs) by improving their osteogenic and angiogenic activities. Previous studies transduced the HIF-1? gene into MSCs with lentivirus vectors to improve their bone healing capacity. However, the risks due to lentivirus vectors, such as tumorigenesis, should be considered before clinical application. Dimethyloxaloylglycine (DMOG) is a cell-permeable prolyl-4-hydroxylase inhibitor, which can activate the expression of HIF-1? in cells at normal oxygen tension. Therefore, DMOG is expected to be an alternative strategy for enhancing HIF-1? expression in cells. In this study, we explored the osteogenic and angiogenic activities of adipose-derived stem cells (ASCs) treated with different concentrations of DMOG in vitro, and the bone healing capacity of DMOG-treated ASCs combined with hydrogels for treating critical-sized calvarial defects in rats. The results showed that DMOG had no obvious cytotoxic effects on ASCs and could inhibit the death of ASCs induced by serum deprivation. DMOG markedly increased vascular endothelial growth factor production in ASCs in a dose-dependent manner and improved the osteogenic differentiation potential of ASCs by activating the expression of HIF-1?. Rats with critical-sized calvarial defects treated with hydrogels containing DMOG-treated ASCs had more bone regeneration and new vessel formation than the other groups. Therefore, we believe that DMOG enhanced the angiogenic and osteogenic activity of ASCs by activating the expression of HIF-1?, thereby improving the bone healing capacity of ASCs in rat critical-sized calvarial defects. PMID:24328551

  19. Positive impact of IGF-1-coupled nanoparticles on the differentiation potential of human chondrocytes cultured on collagen scaffolds

    PubMed Central

    Pasold, Juliane; Zander, Kathleen; Heskamp, Benjamin; Grüttner, Cordula; Lüthen, Frank; Tischer, Thomas; Jonitz-Heincke, Anika; Bader, Rainer

    2015-01-01

    Purpose In the present study, silica nanoparticles (sNP) coupled with insulin-like growth factor 1 (IGF-1) were loaded on a collagen-based scaffold intended for cartilage repair, and the influence on the viability, proliferation, and differentiation potential of human primary articular chondrocytes was examined. Methods Human chondrocytes were isolated from the hyaline cartilage of patients (n=4, female, mean age: 73±5.1 years) undergoing primary total knee joint replacement. Cells were dedifferentiated and then cultivated on a bioresorbable collagen matrix supplemented with fluorescent sNP coupled with IGF-1 (sNP–IGF-1). After 3, 7, and 14 days of cultivation, cell viability and integrity into the collagen scaffold as well as metabolic cell activity and synthesis rate of matrix proteins (collagen type I and II) were analyzed. Results The number of vital cells increased over 14 days of cultivation, and the cells were able to infiltrate the collagen matrix (up to 120 ?m by day 7). Chondrocytes cultured on the collagen scaffold supplemented with sNP–IGF-1 showed an increase in metabolic activity (5.98-fold), and reduced collagen type I (1.58-fold), but significantly increased collagen type II expression levels (1.53-fold; P=0.02) after 7 days of cultivation compared to 3 days. In contrast, chondrocytes grown in a monolayer on plastic supplemented with sNP-IGF-1 had significantly lower metabolic activity (1.32-fold; P=0.007), a consistent amount of collagen type I, and significantly reduced collagen type II protein expression (1.86-fold; P=0.001) after 7 days compared to 3 days. Conclusion Collagen-based scaffolds enriched with growth factors, such as IGF-1 coupled to nanoparticles, represent an improved therapeutic intervention for the targeted and controlled treatment of articular cartilage lesions. PMID:25709437

  20. Differentially Expressed Genes between Early and Advanced Hepatocellular Carcinoma (HCC) as a Potential Tool for Selecting Liver Transplant Recipients

    PubMed Central

    Mas, Valeria R; Maluf, Daniel G; Archer, Kellie J; Yanek, Kenneth; Williams, Bridgette; Fisher, Robert A

    2006-01-01

    Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. Liver transplantation (LT) represents a curative treatment for “small” HCC. Preoperative staging is critical in selecting optimal candidates for LT to optimize the use of this scarce resource. From December 1997 to February 2004, 148 patients diagnosed with cirrhosis and HCC were evaluated at our center. After staging, the patients were listed for LT according to United Network for Organ Sharing (UNOS) criteria. When pretransplant liver MRIs were compared with the findings of the explanted livers, 8 of 35 patients (22.8%) were understaged. Three of the 8 patients (37.5%) had recurrence post-LT. A retrospective gene expression profiling study was done using microarray technology for tumor samples in the pretransplant hepatitis C virus (HCV)-HCC understaged patients and in a contemporaneous group of HCV-HCC patients that were accurately staged. Two sample t tests comparing the early versus advanced HCV-HCCs with respect to gene expression showed an important set of genes differentially expressed among the samples. Hierarchical clustering analysis of the gene expression profiling classified 93.8% of the total tumor samples and 85.7% of the understaged samples in concordance with the explanted pathological staging. We found a distinctive pattern of gene expression between early and advanced HCV-HCCs. These results suggest that gene expression profiling could improve the pre-LT HCC staging to more closely mimic the explant pathology. Whether gene expression profiling of HCC will be refined to the point of predicting potential metastatic biologic behavior to predict post-LT recurrence will require longitudinal prospective study of this gene array technology. PMID:16953559

  1. Novel test method (sickle confirm) to differentiate sickle cell anemia from sickle cell trait for potential use in developing countries.

    PubMed

    Randolph, Tim R; Wheelhouse, Jenna

    2012-01-01

    The objective of this study was to develop a diagnostic testing method to detect HbS, distinguish sickle cell homozygotes from heterozygotes, and overcome testing barriers encountered in laboratories in underdeveloped countries. Blood samples positive and negative for sickle cell were subjected to the standard hemoglobin solubility test followed by a variety of centrifugation and filtration procedures. Each procedure was evaluated for the ability to remove insoluble HbS from the sample. The hemoglobin types that remain (HbA, HbA2 and HbF) were measured spectrophotometrically or estimated visually allowing samples to be categorized into three genotypes (AA, AS and SS) as confirmed by hemoglobin electrophoresis. De-identified EDTA blood samples were obtained from Saint Louis University and Cardinal Glennon Children's hospitals and tested in the Department of Clinical Laboratory Science at Saint Louis University. The main outcome measures were turbidity of the solubility solution; color of the supernatant and the material on the surface of the solution following centrifugation; precipitate trapped on the filter paper; absorbance of the filtrate; and hemoglobin electrophoresis patterns. Centrifugation and filtration successfully separated HbS from HbA/A2/F allowing for the differentiation of seven sickle cell homozygotes from sixteen heterozygotes with a sensitivity and specificity of 100%. This method has the potential to reliably distinguish homozygous from heterozygous sickle cell patients and it is fast, inexpensive, and simple. These characteristics make Sickle Confirm a desirable method in developing countries like Haiti and Africa where sickle cell anemia is prevalent and modern diagnostic methods like electrophoresis, HPLC and nucleic acid testing are impractical. PMID:22458046

  2. 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)

    Bishop, Janice L.; Murad, Enver; Lane, Melissa D.; Mancinelli, Rocco L.

    2004-06-01

    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.

  3. THE EFFECTS OF DIFFERENTIAL REDDENING AND STELLAR ROTATION ON THE APPEARANCE OF MULTIPLE POPULATIONS IN STAR CLUSTERS: THE CASE OF TRUMPLER 20

    SciTech Connect

    Platais, I. [Department of Physics and Astronomy, The Johns Hopkins University, Baltimore, MD 21218 (United States); Melo, C. [European Southern Observatory, Karl-Schwarzschild-Str. 2, 85748 Garching bei Muenchen (Germany); Quinn, S. N.; Latham, D. W. [Harvard-Smithsonian Center for Astrophysics, 60 Garden Street, Cambridge, MA 02138 (United States); Clem, J. L. [Department of Physics and Astronomy, Louisiana State University, Baton Rouge, LA 70803 (United States); De Mink, S. E.; Dotter, A.; Kozhurina-Platais, V. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Bellini, A., E-mail: imants@pha.jhu.edu [Dipartimento di Astronomia, Universita di Padova, Vicolo dell'Osservatorio 3, Padova, I-35122 (Italy)

    2012-05-20

    We present a detailed analysis of the upper main sequence of the {approx}1.3 Gyr old open cluster Trumpler 20. High-accuracy BVI photometry combined with the Very Large Telescope/FLAMES medium-resolution spectroscopy of 954 stars is essential to understanding the unusual appearance of the color-magnitude diagram (CMD), initially suggesting multiple populations in Trumpler 20. We show that differential reddening is a dominant contributor to the apparent splitting/widening of the main-sequence turnoff region. At its extreme, the excess differential reddening reaches {Delta}(B - V) {approx} 0.1 while the adopted minimum reddening for the cluster is E(B - V) = 0.36. A unique sample of measured projected rotational velocities indicates that stellar rotation is high near the main-sequence turnoff, reaching vsin i {approx} 180 km s{sup -1}. By dividing the upper main-sequence stars into two equal groups of slow and fast rotators, we find that fast rotators have a marginal blueshift of {delta}(V - I) {approx} -0.01, corresponding to a difference in the median vsin i of {approx}60 km s{sup -1} between these subsamples. We conclude that stellar rotation has an insignificant effect on the morphology of the upper main sequence of this intermediate-age open cluster. Trumpler 20 appears to contain a single coeval population of stars but there is evidence that the red clump is extended.

  4. Analysis of Multiple Brachyspira hyodysenteriae Genomes Confirms That the Species Is Relatively Conserved but Has Potentially Important Strain Variation

    PubMed Central

    Barrero, Roberto; La, Tom; Phillips, Nyree; Hampson, David; Herbst, Werner; Barth, Stefanie; Bellgard, Matthew

    2015-01-01

    The intestinal spirochete Brachyspira hyodysenteriae is an important pathogen in swine, causing mucohemorrhagic colitis in a disease known as swine dysentery. Based on the detection of significant linkage disequilibrium in multilocus sequence data, the species is considered to be clonal. An analysis of the genome sequence of Western Australian B. hyodysenteriae strain WA1 has been published, and in the current study 19 further strains from countries around the world were sequenced with Illumina technology. The genomes were assembled and aligned to over 97.5% of the reference WA1 genome at a percentage sequence identity better than 80%. Strain regions not aligned to the reference ranged between 0.2 and 2.5%. Clustering of the strain genes found on average 2,354 (88%) core genes, 255 (8.6%) ancillary genes and 77 (2.9%) unique genes per strain. Depending on the strain the proportion of genes with 100% sequence identity to WA1 ranged from 85% to 20%. The result is a global comparative genomic analysis of B. hyodysenteriae genomes revealing potential differential phenotypic markers for numerous strains. Despite the differences found, the genomes were less varied than those of the related pathogenic species Brachyspira pilosicoli, and the analysis supports the clonal nature of the species. From this study, a public genome resource has been created that will serve as a repository for further genetic and phenotypic studies of these important porcine bacteria. This is the first intra-species B. hyodysenteriae comparative genomic analysis. PMID:26098837

  5. Trypanosoma cruzi: Synergistic cytotoxicity of multiple amphipathic anti-microbial peptides to T. cruzi and potential bacterial hosts

    PubMed Central

    Fieck, Annabeth; Hurwitz, Ivy; S.Kang, Angray; Durvasula, Ravi

    2010-01-01

    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

  6. Mouse monoclonal antibodies to transient receptor potential ankyrin 1 act as antagonists of multiple modes of channel activation.

    PubMed

    Lee, Ki Jeong; Wang, Weiya; Padaki, Rupa; Bi, Vivian; Plewa, Cherylene A; Gavva, Narender R

    2014-08-01

    The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in different pathophysiologies that include asthma, cough, itch, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and pain behaviors in rodents. Hence, TRPA1 antagonists are being pursued as potential therapeutics. With the goal of generating monoclonal antibodies (mAbs) to human TRPA1 that could act as selective antagonists, we immunized mice with a variety of antigens expressing TRPA1 channels. After generation of hybridomas, the hybridoma conditioned media were screened to identify the mAbs that bind TRPA1 channels by a flow cytometry assay utilizing U2OS or Chinese hamster ovary (CHO) cells stably expressing TRPA1. The purified IgGs from the hybridomas that showed selective binding to TRPA1 were evaluated for antagonism in agonist-induced (45)Ca(2+) uptake assays using CHO-TRPA1 cells. Several of the mAbs showed concentration-dependent inhibition of AITC and cold (4°C) activation of TRPA1. The most potent mAb, 2B10, had IC50 values of approximately 260 and 90 nM in the two assays, respectively. These antagonist mAbs also blocked osmotically activated TRPA1 as well as activation by an endogenous agonist (4-oxo-2-nonenal). In summary, we generated mouse mAbs against TRPA1 that act as antagonists of multiple modes of TRPA1 activation. PMID:24893987

  7. A composite enhancer regulates p63 gene expression in epidermal morphogenesis and in keratinocyte differentiation by multiple mechanisms.

    PubMed

    Antonini, Dario; Sirico, Anna; Aberdam, Edith; Ambrosio, Raffaele; Campanile, Carmen; Fagoonee, Sharmila; Altruda, Fiorella; Aberdam, Daniel; Brissette, Janice L; Missero, Caterina

    2015-01-01

    p63 is a crucial regulator of epidermal development, but its transcriptional control has remained elusive. Here, we report the identification of a long-range enhancer (p63LRE) that is composed of two evolutionary conserved modules (C38 and C40), acting in concert to control tissue- and layer-specific expression of the p63 gene. Both modules are in an open and active chromatin state in human and mouse keratinocytes and in embryonic epidermis, and are strongly bound by p63. p63LRE activity is dependent on p63 expression in embryonic skin, and also in the commitment of human induced pluripotent stem cells toward an epithelial cell fate. A search for other transcription factors involved in p63LRE regulation revealed that the CAAT enhancer binding proteins Cebpa and Cebpb and the POU domain-containing protein Pou3f1 repress p63 expression during keratinocyte differentiation by binding the p63LRE enhancer. Collectively, our data indicate that p63LRE is composed of additive and partly redundant enhancer modules that act to direct robust p63 expression selectively in the basal layer of the epidermis. PMID:25567987

  8. A composite enhancer regulates p63 gene expression in epidermal morphogenesis and in keratinocyte differentiation by multiple mechanisms

    PubMed Central

    Antonini, Dario; Sirico, Anna; Aberdam, Edith; Ambrosio, Raffaele; Campanile, Carmen; Fagoonee, Sharmila; Altruda, Fiorella; Aberdam, Daniel; Brissette, Janice L.; Missero, Caterina

    2015-01-01

    p63 is a crucial regulator of epidermal development, but its transcriptional control has remained elusive. Here, we report the identification of a long-range enhancer (p63LRE) that is composed of two evolutionary conserved modules (C38 and C40), acting in concert to control tissue- and layer-specific expression of the p63 gene. Both modules are in an open and active chromatin state in human and mouse keratinocytes and in embryonic epidermis, and are strongly bound by p63. p63LRE activity is dependent on p63 expression in embryonic skin, and also in the commitment of human induced pluripotent stem cells toward an epithelial cell fate. A search for other transcription factors involved in p63LRE regulation revealed that the CAAT enhancer binding proteins Cebpa and Cebpb and the POU domain-containing protein Pou3f1 repress p63 expression during keratinocyte differentiation by binding the p63LRE enhancer. Collectively, our data indicate that p63LRE is composed of additive and partly redundant enhancer modules that act to direct robust p63 expression selectively in the basal layer of the epidermis. PMID:25567987

  9. Predators with multiple ontogenetic niche shifts have limited potential for population growth and top-down control of their prey.

    PubMed

    van Leeuwen, Anieke; Huss, Magnus; Gĺrdmark, Anna; Casini, Michele; Vitale, Francesca; Hjelm, Joakim; Persson, Lennart; de Roos, André M

    2013-07-01

    Catastrophic collapses of top predators have revealed trophic cascades and community structuring by top-down control. When populations fail to recover after a collapse, this may indicate alternative stable states in the system. Overfishing has caused several of the most compelling cases of these dynamics, and in particular Atlantic cod stocks exemplify such lack of recovery. Often, competition between prey species and juvenile predators is hypothesized to explain the lack of recovery of predator populations. The predator is then considered to compete with its prey for one resource when small and to subsequently shift to piscivory. Yet predator life history is often more complex than that, including multiple ontogenetic diet shifts. Here we show that no alternative stable states occur when predators in an intermediate life stage feed on an additional resource (exclusive to the predator) before switching to piscivory, because predation and competition between prey and predator do not simultaneously structure community dynamics. We find top-down control by the predator only when there is no feedback from predator foraging on the additional resource. Otherwise, the predator population dynamics are governed by a bottleneck in individual growth occurring in the intermediate life stage. Therefore, additional resources for predators may be beneficial or detrimental for predator population growth and strongly influence the potential for top-down community control. PMID:23778226

  10. Epistatic effects of multiple receptor genes on pathophysiology of asthma – its limits and potential for clinical application

    PubMed Central

    Yoshikawa, Takahiro; Kanazawa, Hiroshi; Fujimoto, Shigeo; Hirata, Kazuto

    2014-01-01

    To date, genome-wide association studies (GWAS) permit a comprehensive scan of the genome in an unbiased manner, with high sensitivity, and thereby have the potential to identify candidate genes for the prevalence or development of multifactorial diseases such as bronchial asthma. However, most studies have only managed to explain a small additional percentage of hereditability estimates, and often fail to show consistent results among studies despite large sample sizes. Epistasis is defined as the interaction between multiple different genes affecting phenotypes. By applying epistatic analysis to clinical genetic research, we can analyze interactions among more than 2 molecules (genes) considering the whole system of the human body, illuminating dynamic molecular mechanisms. An increasing number of genetic studies have investigated epistatic effects on the risk for development of asthma. The present review highlights a concept of epistasis to overcome traditional genetic studies in humans and provides an update of evidence on epistatic effects on asthma. Furthermore, we review concerns regarding recent trends in epistatic analyses from the perspective of clinical physicians. These concerns include biological plausibility of genes identified by computational statistics, and definition of the diagnostic label of ‘physician-diagnosed asthma’. In terms of these issues, further application of epistatic analysis will prompt identification of susceptibility of diseases and lead to the development of a new generation of pharmacological strategies to treat asthma. PMID:24435185

  11. Lateral ventricular cerebrospinal fluid diffusivity as a potential neuroimaging marker of brain temperature in multiple sclerosis: a hypothesis and implications.

    PubMed

    Hasan, Khader M; Lincoln, John A; Nelson, Flavia M; Wolinsky, Jerry S; Narayana, Ponnada A

    2015-04-01

    In this retrospective study we tested the hypothesis that the net effect of impaired electrical conduction and therefore increased heat dissipation in multiple sclerosis (MS) results in elevated lateral ventricular (LV) cerebrospinal fluid (CSF) diffusivity as a measure of brain temperature estimated in vivo using diffusion tensor imaging (DTI). We used validated DTI-based segmentation methods to obtain normalized LV-CSF volume and its corresponding CSF diffusivity in 108 MS patients and 103 healthy controls in the age range of 21-63 years. The LV CSF diffusivity was ~2% higher in MS compared to controls that correspond to a temperature rise of ~1°C that could not be explained by changes in the CSF viscosity due to altered CSF protein content in MS. The LV diffusivity decreased with age in healthy controls (r=-0.29; p=0.003), but not in MS (r=0.15; p=0.11), possibly related to MS pathology. Age-adjusted LV diffusivity increased with lesion load (r=0.518; p=1×10(-8)). Our data suggest that the total brain lesion load is the primary contributor to the increase in LV CSF diffusivity in MS. These findings suggest that LV diffusivity is a potential in vivo biomarker of the mismatch between heat generation and dissipation in MS. We also discuss limitations and possible confounders. PMID:25485790

  12. Alterations of field potentials in isotropic cardiomyocyte cell layers induced by multiple endogenous pacemakers under normal and hypothermal conditions.

    PubMed

    Kienast, R; Stöger, M; Handler, M; Hanser, F; Baumgartner, C

    2014-10-01

    The use of autonomous contracting randomly grown cardiomyocyte monolayers cultivated on microelectrode arrays (MEAs) represents an accepted experimental setting for preclinical experimental research in the field of cardiac electrophysiology. A dominant pacemaker forces a monolayer to adhere to a regular and synchronized contraction. Randomly distributed multiple pacemakers interfere with this dominant center, resulting in more or less frequent changes of propagation direction. This study aims to characterize the impact of changing propagation directions at single electrodes of the MEA on the four intrinsic parameters of registered field potentials (FPs) FPrise, FPMIN, FPpre, and FPdur and conduction velocity (CV) under normal and hypothermal conditions. Primary cultures of chicken cardiomyocytes (n = 18) were plated directly onto MEAs and FPs were recorded in a temperature range between 37 and 29°C. The number and spatiotemporal distribution of biological and artificial pacemakers of each cell layer inside and outside of the MEA registration area were evaluated using an algorithm developed in-house. In almost every second myocardial cell layer, interfering autonomous pacemakers were detected at stable temperatures, showing random spatial distributions with similar beating rates. Additionally, a temperature-dependent change of the dominant pacemaker center was observed in n = 16 experiments. A significant spread-direction-dependent variation of CV, FPrise, FPMIN, and FPpre up to 14% could be measured between different endogenous pacemakers. In conclusion, based on our results, disregarding the spatial origin of excitation may lead to misinterpretations and erroneous conclusions of FP parameters in the verification of research hypotheses in cellular electrocardiology. PMID:25085965

  13. potential of Visible-Near Infrared Spectroscopy for mapping of multiple soil properties using real-time soil sensor

    NASA Astrophysics Data System (ADS)

    Aliah, B. S. N.; Kodaira, M.; Shibusawa, S.

    2013-05-01

    Over the past few decades, scientists have understood the needs for the exploitation of optical means particularly Vis-NIR spectroscopy to measure agriculture soil properties in real-time. The objective of this study is therefore to investigate the potential of Vis-NIR spectroscopy for mapping of multiple (19) soil properties using the optical-based real-time soil sensor (RTSS). For this purpose, Vis-NIR soil reflectance spectra (from 310 to 1700nm) were acquired using a tractor-mounted RTSS at 2 fields of a commercial farm in Hokkaido, Japan. The RTSS consists of a halogen lamp, fiber optics, two spectrophotometers, computer, DGPS receiver, and CCD camera. A total of 262 soil samples were collected subsequently for laboratory chemical analysis. PLSR coupled with full-cross validation was used to establish the relationship between the pre-treated Vis-NIR spectra with the value of soil properties obtained by chemical analysis. From this analysis, it was found that the accuracy of the calibration models ranged from Rval2 of 0.65 to 0.86 and RPD from 1.7 to 2.7, meaning that the accuracy some of the models were excellent and others were almost good. Moreover, the predicted maps of 19 soil properties were comparable with the measured map. This shows that the RTSS by means of Vis-NIR spectroscopy can be used for mapping the 19 soil properties.

  14. Analyses of the differentiation potential of satellite cells from myoD-/-, mdx, and PMP22 C22 mice

    PubMed Central

    Schuierer, Marion M; Mann, Christopher J; Bildsoe, Heidi; Huxley, Clare; Hughes, Simon M

    2005-01-01

    Background Sporadic and sometimes contradictory studies have indicated changes in satellite cell behaviour associated with the progressive nature of human Duchenne muscular dystrophy (DMD). Satellite cell proliferation and number are reportedly altered in DMD and the mdx mouse model. We recently found that satellite cells in MSVski transgenic mice, a muscle hypertrophy model showing progressive muscle degeneration, display a severe ageing-related differentiation defect in vitro. We tested the hypothesis that similar changes contribute to the gradual loss of muscle function with age in mdx and PMP22 mice, a model of human motor and sensory neuropathy type 1A (HMSN1A). Methods Single extensor digitorum longus muscle fibres were cultured from mdx and PMP22 mice and age- and genetic background-matched controls. Mice at several ages were compared with regard to the differentiation of satellite cells, assayed as the proportion of desmin-expressing cells that accumulated sarcomeric myosin heavy chain. Results Satellite cells of 2 month, 6 month, and 12 month old mdx mice were capable of differentiating to a similar extent to age-matched wild type control animals in an in vitro proliferation/differentiation model. Strikingly, differentiation efficiency in individual 6 month and 12 month old mdx animals varies to a much higher extent than in age-matched controls, younger mdx animals, or PMP22 mice. In contrast, differentiation of myoblasts from all myoD null mice assayed was severely impaired in this assay system. The defect in satellite cell differentiation that occurs in some mdx animals arises from a delay in differentiation that is not overcome by IGF-1 treatment at any phase of cultivation. Conclusion Overall, a defect in satellite cell differentiation above that arising through normal ageing does not occur in mdx or PMP22 mouse models of human disease. Nonetheless, the impaired differentiation of satellite cells from some mdx animals suggests that additional factors, environmental or epigenetic, may lead to deteriorating muscle repair through poor differentiation of satellite cells in genetically predisposed individuals. PMID:15762989

  15. Differentiation Potential of O Bombay Human-Induced Pluripotent Stem Cells and Human Embryonic Stem Cells into Fetal Erythroid-Like Cells

    PubMed Central

    Ganji, Fatemeh; Abroun, Saeid; Baharvand, Hossein; Aghdami, Nasser; Ebrahimi, Marzieh

    2015-01-01

    Objective There is constant difficulty in obtaining adequate supplies of blood components, as well as disappointing performance of "universal" red blood cells. Advances in somatic cell reprogramming of human-induced pluripotent stem cells (hiPSCs) have provided a valuable alternative source to differentiate into any desired cell type as a therapeutic promise to cure many human disease. Materials and Methods In this experimental study, we examined the erythroid differentiation potential of normal Bombay hiPSCs (B-hiPSCs) and compared results to human embryonic stem cell (hESC) lines. Because of lacking ABO blood group expression in B-hiPSCs, it has been highlighted as a valuable source to produce any cell type in vitro. Results Similar to hESC lines, hemangioblasts derived from B-hiPSCs expressed approximately 9% KDR+CD31+ and approximately 5% CD31+CD34+. In semisolid media, iPSC and hESC-derived hemangioblast formed mixed type of hematopoietic colony. In mixed colonies, erythroid progenitors were capable to express CD71+GPA+HbF+ and accompanied by endothelial cells differentiation. Conclusion Finally, iPS and ES cells have been directly induced to erythropoiesis without hemangioblast formation that produced CD71+HbF+ erythroid cells. Although we observed some variations in the efficiency of hematopoietic differentiation between iPSC and ES cells, the pattern of differentiation was similar among all three tested lines. PMID:25685733

  16. Mitochondrial analysis of a Byzantine population reveals the differential impact of multiple historical events in South Anatolia

    PubMed Central

    Ottoni, Claudio; Ricaut, François-X; Vanderheyden, Nancy; Brucato, Nicolas; Waelkens, Marc; Decorte, Ronny

    2011-01-01

    The archaeological site of Sagalassos is located in Southwest Turkey, in the western part of the Taurus mountain range. Human occupation of its territory is attested from the late 12th millennium BP up to the 13th century AD. By analysing the mtDNA variation in 85 skeletons from Sagalassos dated to the 11th–13th century AD, this study attempts to reconstruct the genetic signature potentially left in this region of Anatolia by the many civilizations, which succeeded one another over the centuries until the mid-Byzantine period (13th century BC). Authentic ancient DNA data were determined from the control region and some SNPs in the coding region of the mtDNA in 53 individuals. Comparative analyses with up to 157 modern populations allowed us to reconstruct the origin of the mid-Byzantine people still dwelling in dispersed hamlets in Sagalassos, and to detect the maternal contribution of their potential ancestors. By integrating the genetic data with historical and archaeological information, we were able to attest in Sagalassos a significant maternal genetic signature of Balkan/Greek populations, as well as ancient Persians and populations from the Italian peninsula. Some contribution from the Levant has been also detected, whereas no contribution from Central Asian population could be ascertained. PMID:21224890

  17. Differential neuroprotective potential of CRMP2 peptide aptamers conjugated to cationic, hydrophobic, and amphipathic cell penetrating peptides

    PubMed Central

    Moutal, Aubin; François-Moutal, Liberty; Brittain, Joel M.; Khanna, May; Khanna, Rajesh

    2015-01-01

    The microtubule-associated axonal specification collapsin response mediator protein 2 (CRMP2) is a novel target for neuroprotection. A CRMP2 peptide (TAT-CBD3) conjugated to the HIV transactivator of transcription (TAT) protein’s cationic cell penetrating peptide (CPP) motif protected neurons in the face of toxic levels of Ca2+ influx leaked in via N-methyl-D-aspartate receptor (NMDAR) hyperactivation. Here we tested whether replacing the hydrophilic TAT motif with alternative cationic (nona-arginine (R9)), hydrophobic (membrane transport sequence (MTS) of k-fibroblast growth factor) or amphipathic (model amphipathic peptide (MAP)) CPPs could be superior to the neuroprotection bestowed by TAT-CBD3. In giant plasma membrane vesicles (GPMVs) derived from cortical neurons, the peptides translocated across plasma membranes with similar efficiencies. Cortical neurons, acutely treated with peptides prior to a toxic glutamate challenge, demonstrated enhanced efflux of R9-CBD3 compared to others. R9-CBD3 inhibited N-methyl-D-aspartate (NMDA)-evoked Ca2+ influx to a similar extent as TAT-CBD3 while MTS-CBD3 was ineffective which correlated with the ability of R9- and TAT-CBD3, but not MTS-CBD3, to block NMDAR interaction with CRMP2. Unrestricted Ca2+ influx through NMDARs leading to delayed calcium dysregulation and neuronal cell death was blocked by all peptides but MAP-CBD3. When applied acutely for 10 min, R9-CBD3 was more effective than TAT-CBD3 at neuroprotection while MTS- and MAP-CBD3 were ineffective. In contrast, long-term (>24 h) treatment with MTS-CBD3 conferred neuroprotection where TAT-CBD3 failed. Neither peptide altered surface trafficking of NMDARs. Neuroprotection conferred by MTS-CBD3 peptide is likely due to its increased uptake coupled with decreased efflux when compared to TAT-CBD3. Overall, our results demonstrate that altering CPPs can bestow differential neuroprotective potential onto the CBD3 cargo. PMID:25674050

  18. Validity of approximate methods in molecular scattering. III - Effective potential and coupled states approximations for differential and gas kinetic cross sections

    NASA Technical Reports Server (NTRS)

    Monchick, L.; Green, S.

    1977-01-01

    Two dimensionality-reducing approximations, the j sub z-conserving coupled states (sometimes called the centrifugal decoupling) method and the effective potential method, were applied to collision calculations of He with CO and with HCl. The coupled states method was found to be sensitive to the interpretation of the centrifugal angular momentum quantum number in the body-fixed frame, but the choice leading to the original McGuire-Kouri expression for the scattering amplitude - and to the simplest formulas - proved to be quite successful in reproducing differential and gas kinetic cross sections. The computationally cheaper effective potential method was much less accurate.

  19. ERK2 protein regulates the proliferation of human mesenchymal stem cells without affecting their mobilization and differentiation potential

    SciTech Connect

    Carcamo-Orive, Ivan; Tejados, Naiara; Delgado, Jesus; Gaztelumendi, Ainhoa [Fundacion Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Department, Paseo Mikeletegi, 61 Bajo 20009, San Sebastian (Spain); Otaegui, David [Unidad Experimental, Hospital Donostia, San Sebastian (Spain); Lang, Valerie [Proteomics Unit, CIC bioGUNE, Ed. 801A Parque Tecnologico de Bizkaia, Derio 48160 (Spain); Trigueros, Cesar [Fundacion Inbiomed, Foundation for Stem Cell Research, Mesenchymal Stem Cell Department, Paseo Mikeletegi, 61 Bajo 20009, San Sebastian (Spain)], E-mail: ctrigueros@inbiomed.org

    2008-05-01

    Human Mesenchymal Stem Cells (hMSC), derived mainly from adult bone marrow, are valuable models for the study of processes involved in stem cell self-renewal and differentiation. As the Extracellular signal-Regulated Kinase (ERK) signalling pathway is a major contributor to cellular growth, differentiation and survival, we have studied the functions of this kinase in hMSC activity. Ablation of ERK2 gene expression (but not ERK1) by RNA interference significantly reduced proliferation of hMSC. This reduction was due to a defect in Cyclin D1 expression and subsequent arrest in the G0/G1 phase of the cell cycle. hMSC growth is enhanced through culture medium supplementation with growth factors (GFs) such as Platelet-Derived Growth Factor (PDGF), basic Fibroblast Growth Factor (bFGF) or Epidermal Growth Factor (EGF). However, these supplements could not rescue the defect observed after ERK2 knockdown, suggesting a common signalling pathway used by these GFs for proliferation. In contrast, ERK1/2 may be dissociated from chemotactic signalling induced by the same GFs. Additionally, hMSCs were capable of differentiating into adipocytes even in the absence of either ERK1 or ERK2 proteins. Our data show that hMSCs do not require cell division to enter the adipogenic differentiation process, indicating that clonal amplification of these cells is not a critical step. However, cell-cell contact seems to be an essential requirement to be able to differentiate into mature adipocytes.

  20. Mangiferin Reduces the Inhibition of Chondrogenic Differentiation by IL-1? in Mesenchymal Stem Cells from Subchondral Bone and Targets Multiple Aspects of the Smad and SOX9 Pathways

    PubMed Central

    Huh, Jeong-Eun; Koh, Pil-Seong; Seo, Byung-Kwan; Park, Yeon-Chul; Baek, Yong-Hyun; Lee, Jae-Dong; Park, Dong-Suk

    2014-01-01

    Mangiferin is a natural immunomodulator found in plants including mango trees. The effects of mangiferin on chondrogenesis and cartilage repair have not yet been reported. This study was designed to determine the effect of mangiferin on chondrogenic differentiation in IL-1?-stimulated mesenchymal stem cells (MSCs) from subchondral bone and to explore the mechanisms underlying these effects. MSCs were isolated from the subchondral bone of rabbit and treated with mangiferin alone and/or interleukin-1? (IL-1?). Mangiferin induced chondrogenic differentiation in MSCs by upregulating transforming growth factor (TGF)-?, bone morphogenetic protein (BMP)-2, and BMP-4 and several key markers of chondrogenesis, including sex-determining region Y–box (SRY-box) containing gene 9 (SOX9), type 2?1 collagen (Col2?1), cartilage link protein, and aggrecan. In IL-1?-stimulated MSCs, mangiferin significantly reversed the production of TGF-?, BMP-2, BMP-4, SOX9, Col2?1, cartilage link protein, and aggrecan, as well as matrix metalloproteinase (MMP)-1, MMP-13, and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS5). Mangiferin upregulated the phosphorylation of Smad 2, Smad 3, Smad 1/5/8, and SOX9 in IL-1?-stimulated MSCs. In the presence of mangiferin, SOX9 siRNA suppressed the activation of Smad 2, Smad 3, Smad 1/5/8, aggrecan, and Col2?1 expression. In conclusion, mangiferin exhibits both chondrogenic and chondroprotective effects on damaged MSCs and mediates these effects by targeting multiple aspects of the Smad and SOX9 signaling pathways. PMID:25216336

  1. Demonstration of differential quantitative requirements for NSF among multiple vesicle fusion pathways of GLUT4 using a dominant-negative ATPase-deficient NSF

    SciTech Connect

    Chen Xiaoli [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Matsumoto, Hideko [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Hinck, Cynthia S. [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Al-Hasani, Hadi [Institute of Biochemistry, University of Cologne, Cologne (Germany); St-Denis, Jean-Francois [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States); Whiteheart, Sidney W. [Department of Molecular and Cellular Biochemistry, University of Kentucky, Lexington, KY (United States); Cushman, Samuel W. [Experimental Diabetes, Metabolism, and Nutrition Section, Diabetes Branch, NIDDK, NIH, Bethesda, MD (United States)]. E-mail: sam_cushman@nih.gov

    2005-07-22

    In this study, we investigated the relative participation of N-ethylmaleimide-sensitive factor (NSF) in vivo in a complex multistep vesicle trafficking system, the translocation response of GLUT4 to insulin in rat adipose cells. Transfections of rat adipose cells demonstrate that over-expression of wild-type NSF has no effect on total, or basal and insulin-stimulated cell-surface expression of HA-tagged GLUT4. In contrast, a dominant-negative NSF (NSF-D1EQ) can be expressed at a low enough level that it has little effect on total HA-GLUT4, but does reduce both basal and insulin-stimulated cell-surface HA-GLUT4 by {approx}50% without affecting the GLUT4 fold-translocation response to insulin. However, high expression levels of NSF-D1EQ decrease total HA-GLUT4. The inhibitory effect of NSF-D1EQ on cell-surface HA-GLUT4 is reversed when endocytosis is inhibited by co-expression of a dominant-negative dynamin (dynamin-K44A). Moreover, NSF-D1EQ does not affect cell-surface levels of constitutively recycling GLUT1 and TfR, suggesting a predominant effect of low-level NSF-D1EQ on the trafficking of GLUT4 from the endocytic recycling compared to the intracellular GLUT4-specific compartment. Thus, our data demonstrate that the multiple fusion steps in GLUT4 trafficking have differential quantitative requirements for NSF activity. This indicates that the rates of plasma and intracellular membrane fusion reactions vary, leading to differential needs for the turnover of the SNARE proteins.

  2. Detection of correlated dynamics on multiple timescales by measurement of the differential relaxation of zero- and double-quantum coherences involving sidechain methyl groups in proteins

    NASA Astrophysics Data System (ADS)

    Del Rio, Armando; Anand, Aditi; Ghose, Ranajeet

    2006-05-01

    Multiple effects may lead to significant differences between the relaxation rates of zero-quantum coherences (ZQC) and double-quantum coherences (DQC) generated between a pair of nuclei in solution. These include the interference between the anisotropic chemical shifts of the two nuclei participating in formation of the ZQC or DQC, the individual dipolar interactions of each of the two nuclei with the same proton, and the slow modulation of the isotropic chemical shifts of the two nuclei due to conformational exchange. Motional events that occur on a timescale much faster than the rotational correlation time (ps-ns) influence the first two effects, while the third results from processes that occur on a far slower timescale (?s-ms). An analysis of the differential relaxation of ZQC and DQC is thus informative about dynamics on the fast as well as the slow timescales. We present here an experiment that probes the differential relaxation of ZQC and DQC involving methyl groups in protein sidechains as an extension to our recently proposed experiments for the protein backbone. We have applied the methodology to 15N, 13C-labeled ubiquitin and used a detailed analysis of the measured relaxation rates using a simple single-axis diffusion model to probe the motional restriction of the C nextH next bond vector where C next is the carbon that is directly bonded to a sidechain methyl carbon (C methyl). Comparison of the present results with the motional restriction of the C nextC methyl bond (Saxis2) reveals that the single-axis diffusion model, while valid in the fringes of the protein and for shorter chain amino acids, proves inadequate in the central protein core for long chain, asymmetrically branched amino acids where more complex motional models are necessary, as is the inclusion of the possibility of correlation between multiple motional modes. In addition, the present measurements report on the modulation of isotropic chemical shifts due to motion on the ?s-ms timescale. Three Leu residues (8, 50, and 56) are found to display these effects. These residues lie in regions where chemical shift modulation had been detected previously both in the backbone and sidechain regions of ubiquitin.

  3. Therapeutic potentials occurring during the early differentiation process of mesenchymal stem cells in a rats model with thioacetamide-induced liver fibrosis

    PubMed Central

    Choi, Sang-Tae; Hong, Hea-Nam; Won, You-Jin; Ahn, Chul-Soo; Ha, Tae-Yong; Song, Gi-Won; Jung, Dong-Hwan; Park, Gil-Chun; Lee, Sung-Gyu

    2013-01-01

    Backgrounds/Aims Mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, The purpose of this study is to investigate the MSCs' differentiation process and therapeutic potentials by comparing isolated MSCs with HGF-treated MSCs in rat's model with thiacetamide (TAA)-induced cirrhosis. Methods Male Sprague-Dawley (SD) rats, weighing 100-150 g were used in this study. To induce liver fibrosis, recipient rats were taken with 0.04% thioacetamide (TAA) in the drinking water (400 mg TAA/L) for 8 weeks. The rats underlying liver cirrhosis were divided into 3 groups according to the transplanted materials, compared to normal saline as control (I) and isolated MSCs (II) HGF-treated MSCs. Results Severe hepatic fibrosis and hepatocyte destruction were detected in the control group. Less hepatic cirrhosis and collagen formation, more hepatocyte regeneration and glycogen storage were detected in isolated MSCs compared to HGF-treated MSCs group, Distribution of red autofluorescence is mainly localized near the sinusoids in isolated MSCs, scattered away the sinusoids in HGF-treated MSCs group. MSCs transdifferentiated into CK-19 postive Oval cells and then to albulmin-producing hepatocytes, HGF treated MSCs differentiated into hepatocyte without the intermediate oval cells phase. HGF treated MSCs became the CK18-positive, MSCs became CD 90-positive. Conclusions Significant hepatocyte differentiation occurred in not HGF-treated MSCs but isolated MSCs group unexpectedly. These results suggest that the beneficial effect of MSCs on in rat's model with TAA-induced cirrhosis may occur during early differentiation course of MSCs. Mature hepatocyte itself has a little effect on the accelerated differentiation and functional capacity of hepatic lineage cell-line.

  4. Modulation of the migration and differentiation potential of adult bone marrow stromal stem cells by nitric oxide

    Microsoft Academic Search

    John W. Fuseler; Mani T. Valarmathi

    Nitric oxide (NO) is a diffusible free radical, which serves as a pluripotent intracellular messenger in numerous cell systems. NO has been demonstrated to regulate actin dependent cellular functions and functions as a putative inductive agent in directing stem cells differentiation. In this study, we investigated the effect of exogenous NO on the kinetics of movement and morphological changes in

  5. A feasibility study of an in vitro differentiation potential toward insulin-producing cells by dental tissue-derived mesenchymal stem cells.

    PubMed

    Sawangmake, Chenphop; Nowwarote, Nunthawan; Pavasant, Prasit; Chansiripornchai, Piyarat; Osathanon, Thanaphum

    2014-09-26

    Dental tissue-derived mesenchymal stem cells have been proposed as an alternative source for mesenchymal stem cells. Here, we investigated the differentiation ability toward insulin producing cells (IPCs) of human dental pulp stem cells (hDPSCs) and human periodontal ligament stem cells (hPDLSCs). These cells expressed mesenchymal stem cell surface markers and were able to differentiate toward osteogenic and adipogenic lineages. Upon 3 step-IPCs induction, hDPSCs exhibited more colony number than hPDLSCs. The mRNA upregulation of pancreatic endoderm/islet markers was noted. However, the significant increase was noted only for PDX-1, NGN-3, and INSULIN mRNA expression of hDPSCs. The hDPSCs-derived IPCs expressed PRO-INSULIN and released C-PEPTIDE upon glucose stimulation in dose-dependent manner. After IPCs induction, the Notch target, HES-1 and HEY-1, mRNA expression was markedly noted. Notch inhibition during the last induction step or throughout the protocol disturbed the ability of C-PEPTIDE release upon glucose stimulation. The results suggested that hDPSCs had better differentiation potential toward IPCs than hPDLSCs. In addition, the Notch signalling might involve in the differentiation regulation of hDPSCs into IPCs. PMID:25181343

  6. Isolation of Two Unknown Genes Potentially Involved in Differentiation of the Hematopoietic Pathway, and Studies of Spermidine/Spermine Acetyltransferase Regulation

    SciTech Connect

    Kubera, C.; Gavin, I.; Huberman, E.

    2002-01-01

    Differential display identified a number of candidate genes involved with growth and differentiation in the human leukemia cell lines HL-60 and HL-525. Two of these genes were previously unknown, and one is the gene for the enzyme spermidine/spermine acetyltransferase (SSAT). One of our objectives is to isolate and sequence the unknown genes, 631A1 and 510C1, in order to characterize them and determine their functions. The other is to determine how SSAT is regulated, and look at how the polyamines that SSAT regulates effect macrophage differentiation. By screening the CEM T-cell DNA library and the fetal brain library, we were able to identify clones that had inserts with homology to the 631A1 cDNA probe sequence. The insert was amplified using the polymerase chain reaction (PCR) and is currently being sent to the University of Chicago for automated sequencing. The library screens for 510C1 are currently underway, but hybridization of the 510C1 cDNA probe with nylon membranes containing CEM library phage DNA produced strong signal, indicating the gene is there. SSAT experiments identified that the rate-limiting enzyme that marks the polyamines spermidine and spermine for degradation is regulated by PKC and a transcription factor called Nrf2. The knowledge of regulation and function of these genes involved in macrophage differentiation will provide new insight into this cellular process, potentially making it possible to discover the roots of the problems that cause cancerous diseases.

  7. A novel human high-risk ependymoma stem cell model reveals the differentiation inducing potential of the histone deacetylase inhibitor Vorinostat

    PubMed Central

    Milde, Till; Kleber, Susanne; Korshunov, Andrey; Witt, Hendrik; Hielscher, Thomas; Koch, Philipp; Kopp, Hans-Georg; Jugold, Manfred; Deubzer, Hedwig E.; Oehme, Ina; Lodrini, Marco; Gröne, Hermann-Josef; Benner, Axel; Brüstle, Oliver; Gilbertson, Richard J.; von Deimling, Andreas; Kulozik, Andreas E.; Pfister, Stefan M.; Martin-Villalba, Ana; Witt, Olaf

    2013-01-01

    Incompletely resectable ependymomas are associated with a poor prognosis despite intensive radio- and chemotherapy. Novel treatments have been difficult to develop due to the lack of appropriate models. Here, we report on the generation of a high risk cytogenetic group 3 and molecular group C ependymoma model (DKFZ-EP1NS) which is based on primary ependymoma cells obtained from a patient with metastatic disease. This model displays stem cell features like self renewal capacity, differentiation capacity and specific marker expression. In vivo transplantation showed a high tumorigenic potential of these cells, and xenografts phenotypically recapitulated the original tumor in a niche dependent manner. DKFZ-EP1NS cells harbor transcriptome plasticity, enabling a shift from a neural stem cell-like program towards a profile of primary ependymoma tumor upon in vivo transplantation. Serial transplantation of DKFZ-EP1NS cells from orthotopic xenografts yielded secondary tumors in half the time compared to the initial transplantation. The cells were resistant to temozolomide, vincristine and cisplatin, but responded to histone deacetylase inhibitor (HDACi)-treatment in therapeutically achievable concentrations. In vitro treatment of DKFZ-EP1NS cells with the HDACi Vorinostat induced neuronal differentiation associated with loss of stem cell-specific properties. In summary, this is the first ependymoma model of a cytogenetic group 3 and molecular subgroup C ependymoma based on a human cell line with stem cell-like properties, which we used to demonstrate the differentiation inducing therapeutic potential of HDACi. PMID:21863243

  8. Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus

    Microsoft Academic Search

    Mohammad Reza Palizvan; Yaghoub Fathollahi; Saeed Semnanian; Sohrab Hajezadeh; Javad Mirnajafizadh

    2001-01-01

    The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of ? pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48–144 h (early phase) and 30–33 days

  9. Downregulation of PPAR? by miR-548d-5p suppresses the adipogenic differentiation of human bone marrow mesenchymal stem cells and enhances their osteogenic potential

    PubMed Central

    2014-01-01

    Background Human bone marrow mesenchymal stem cells (hBMSCs) are multipotent cells that can differentiate into a variety of cell types. Elevated expression of peroxisome proliferator-activated receptor-? (PPAR?) promotes the adipogenic differentiation of hBMSCs, and reduces their osteogenic differentiation. MicroRNAs (miRNAs) have been shown to play important roles in the regulation of hBMSCs differentiation. Because bioinformatic analysis has indicated that PPAR? is a candidate target of miR-548d-5p, the aim of this study was to assess the impact of miR-548d-5p on the dexamethasone-induced adipogenic differentiation of hBMSCs. Methods A quantitative RT-PCR (qRT-PCR) assay was used to compare miR-548d-5p expression levels in dexamethasone-induced hBMSCs and uninduced control cells. Oil red O staining, cellular triglyceride (TG) content, and the mRNA and protein levels of PPAR? and CCAAT/enhancer binding protein ? (C/EBP?) were used to evaluate the adipogenic differentiation of hBMSCs. Alkaline phosphatase (ALP) activity and levels of osteocalcin (OCN) and Runx2 were used to evaluate the osteogenic potential of hBMSCs. Results Compared with untreated cells, miR-548d-5p expression levels were downregulated during dexamethasone-induced adipogenic differentiation of hBMSCs. In contrast to the profuse Oil Red O staining in the cytoplasm of dexamethasone?+?scrambled miRNA-treated cells, there was limited staining in the cytoplasm of dexamethasone?+?miR-548d-5p-treated cells, indicating the absence of adipocytes. Moreover, compared with scrambled miRNA-treated cells, treatment with miR-548d-5p suppressed cellular levels of PPAR? and C/EBP? mRNA and protein, and cell TG content (P?differentiation of hBMSCs. By directly targeting and downregulating PPAR?, miR-548d-5p suppresses the dexamethasone-induced adipogenic differentiation of hBMSCs and enhances their osteogenic potential. Our findings suggest that miR-548d-5p has potential in the treatment of corticosteroid-induced osteonecrosis of the femoral head. PMID:24929254

  10. Assessment of pluripotency and multilineage differentiation potential of NTERA-2 cells as a model for studying human embryonic stem cells.

    PubMed

    Pal, Rajarshi; Ravindran, Geeta

    2006-12-01

    Embryonal carcinoma cells are pluripotent stem cells derived from teratocarcinomas and are considered to be the malignant counterparts of human embryonic stem cells. As there are few reliable experimental systems available to study the molecular mechanisms governing normal embryogenesis, well-characterized human embryonal carcinoma stem cell lines may provide a robust and simple model to study certain aspects of pluripotency and cellular differentiation. Here, we have analysed NTERA-2 cL.D1 cells at molecular and cellular levels during expansion and differentiation, via formation of cell aggregates similar to embryoid bodies in embryonic stem cells. Thus, human embryonal carcinoma cells may provide a valuable insight into cell fate determination, into the embryonic ectoderm, mesoderm and endoderm and their downstream derivatives. PMID:17109641

  11. Differential elastic scattering of He* (21S) by Ar, Kr and Xe: Repulsive rainbows and optical potentials

    Microsoft Academic Search

    D. W. Martin; R. W. Gregor; R. M. Jordan; P. E. Siska

    1978-01-01

    Elastic scattering angular distributions of He* (21S) with Ar, Kr, and Xe measured in crossed atomic beams at collision energies from 0.4–2.8 kcal\\/mole are analyzed using a physically motivated optical potential model. The resulting potentials show some features expected on the basis of the analogous Li–rare gas potentials: monotonically increasing van der Waals well depths &egr; in the sequence Ar,

  12. Differential elastic scattering of He* (21S) by Ar, Kr and Xe: Repulsive rainbows and optical potentials

    Microsoft Academic Search

    D. W. Martin; R. W. Gregor; R. M. Jordan; P. E. Siska

    1978-01-01

    Elastic scattering angular distributions of He* (2ÂąS) with Ar, Kr, and Xe measured in crossed atomic beams at collision energies from 0.4--2.8 kcal\\/mole are analyzed using a physically motivated optical potential model. The resulting potentials show some features expected on the basis of the analogous Li--rare gas potentials: monotonically increasing van der Waals well depths epsilon in the sequence Ar,

  13. Experimental study of the potential use of diffusing wave spectroscopy to investigate the structural characteristics of blood under multiple scattering

    Microsoft Academic Search

    Alexander N. Korolevich; Igor V. Meglinsky

    2000-01-01

    The extension of the photon correlation spectroscopy (PCS) in multiple scattering regime, so-called diffusing wave spectroscopy (DWS) was employed to the study of blood samples. Multiple scattered light from a helium–neon (He–Ne) laser beam incident on the blood samples was detected by a photomultiplier, and both the temporal autocorrelation intensity functions g2(?) and power spectra S(?) were measured by a

  14. Comparative Proteomics of Colon Cancer Stem Cells and Differentiated Tumor Cells Identifies BIRC6 as a Potential Therapeutic Target*

    PubMed Central

    Van Houdt, WJ; Emmink, BL; Pham, TV; Piersma, SR; Verheem, A; Vries, RG; Fratantoni, SA; Pronk, A; Clevers, H; Borel Rinkes, IHM; Jimenez, CR; Kranenburg, O

    2011-01-01

    Patients with liver metastases from colon carcinoma show highly variable responses to chemotherapy and tumor recurrence is frequently observed. Therapy-resistant cancer stem cells have been implicated in drug resistance and tumor recurrence. However, the factors determining therapy resistance and tumor recurrence are poorly understood. The aim of this study was to gain insight into these mechanisms by comparing the proteomes of patient-derived cancer stem cell cultures and their differentiated isogenic offspring. We established colonosphere cultures derived from resection specimens of liver metastases in patients with colon cancer. These colonospheres, enriched for colon cancer stem cells, were used to establish isogenic cultures of stably differentiated nontumorigenic progeny. Proteomics based on one-dimensional gel electrophoresis coupled to nano liquid chromatography tandem MS was used to identify proteome differences between three of these paired cultures. The resulting data were analyzed using Ingenuity Pathway Software. Out of a total data set of 3048 identified proteins, 32 proteins were at least twofold up-regulated in the colon cancer stem cells when compared with the differentiated cells. Pathway analysis showed that “cell death ” regulation is strikingly different between the two cell types. Interestingly, one of the top-up-regulated proteins was BIRC6, which belongs to the class of Inhibitor of Apoptosis Proteins. Knockdown of BIRC6 sensitized colon cancer stem cells against the chemotherapeutic drugs oxaliplatin and cisplatin. This study reveals that differentiation of colon cancer stem cells is accompanied by altered regulation of cell death pathways. We identified BIRC6 as an important mediator of cancer stem cell resistance against cisplatin and oxaliplatin. Targeting BIRC6, or other Inhibitors of Apoptosis Proteins, may help eradicating colon cancer stem cells. PMID:21788403

  15. Differential transcript regulation in Arabidopsis thaliana and the halotolerant Lobularia maritima indicates genes with potential function in plant salt adaptation.

    PubMed

    Popova, Olga V; Yang, Oksoon; Dietz, Karl-Josef; Golldack, Dortje

    2008-11-01

    Salt stress is an environmental factor that severely impairs plant growth and productivity. Salinity-induced transcript accumulation was monitored in the salt-sensitive Arabidopsis thaliana and the related salt-tolerant Lobularia maritima using cDNA-arrays with expressed sequence tags derived from a cDNA subtraction library of salt-stressed L. maritima. The expression profiles revealed differences of the steady state transcript regulation in A. thaliana and L. maritima in response to salt stress. The differentially expressed transcripts include those involved in the control of gene expression as a transcription factor II homologue as well as signal transduction elements such as a serine/threonine protein kinase, a SNF1-related protein kinase AKIN10 homologue, and protein phosphatase 2C. Other ESTs with differential regulation patterns included transcripts encoding proteins with function in general stress responses and defense and included a peroxidase, dehydrins, enzymes of lipid and nitrogen metabolism, and functionally unclassified proteins. In a more detailed analysis the basic leucine zipper transcription factor AtbZIP24 showed differential transcript abundance in A. thaliana and L. maritima in response to salt stress. Transgenic AtbZIP24-RNAi lines showed improved growth and development under salt stress that was correlated with changed Cl(-) accumulation. The data indicate that AtbZIP24 functions as a transcriptional repressor in salt-stressed A. thaliana that negatively regulates growth and development under salinity in context of controlling Cl(-) homeostasis. Monitoring the differential and tissue specific global regulation of gene expression during adaptation to salinity in salt-sensitive and halotolerant plants is a promising and powerful approach to identify novel elements of plant salt stress adaptation. PMID:18703123

  16. The Application of Multiobjective Genetic Algorithm to the Parameter Optimization of Single-Well Potential Stochastic Resonance Algorithm Aimed at Simultaneous Determination of Multiple Weak Chromatographic Peaks

    PubMed Central

    Xiang, Bingren; Wu, Xiaohong; Liu, Dan

    2014-01-01

    Simultaneous determination of multiple weak chromatographic peaks via stochastic resonance algorithm attracts much attention in recent years. However, the optimization of the parameters is complicated and time consuming, although the single-well potential stochastic resonance algorithm (SSRA) has already reduced the number of parameters to only one and simplified the process significantly. Even worse, it is often difficult to keep amplified peaks with beautiful peak shape. Therefore, multiobjective genetic algorithm was employed to optimize the parameter of SSRA for multiple optimization objectives (i.e., S/N and peak shape) and multiple chromatographic peaks. The applicability of the proposed method was evaluated with an experimental data set of Sudan dyes, and the results showed an excellent quantitative relationship between different concentrations and responses. PMID:24526920

  17. The application of multiobjective genetic algorithm to the parameter optimization of single-well potential stochastic resonance algorithm aimed at simultaneous determination of multiple weak chromatographic peaks.

    PubMed

    Deng, Haishan; Xie, Shaofei; Xiang, Bingren; Zhan, Ying; Li, Wei; Li, Xiaohua; Jiang, Caiyun; Wu, Xiaohong; Liu, Dan

    2014-01-01

    Simultaneous determination of multiple weak chromatographic peaks via stochastic resonance algorithm attracts much attention in recent years. However, the optimization of the parameters is complicated and time consuming, although the single-well potential stochastic resonance algorithm (SSRA) has already reduced the number of parameters to only one and simplified the process significantly. Even worse, it is often difficult to keep amplified peaks with beautiful peak shape. Therefore, multiobjective genetic algorithm was employed to optimize the parameter of SSRA for multiple optimization objectives (i.e., S/N and peak shape) and multiple chromatographic peaks. The applicability of the proposed method was evaluated with an experimental data set of Sudan dyes, and the results showed an excellent quantitative relationship between different concentrations and responses. PMID:24526920

  18. Low Osteogenic Differentiation Potential of Placenta-Derived Mesenchymal Stromal Cells Correlates with Low Expression of the Transcription Factors Runx2 and Twist2

    PubMed Central

    Ulrich, Christine; Rolauffs, Bernd; Abele, Harald; Bonin, Michael; Nieselt, Kay; Hart, Melanie L.

    2013-01-01

    Recent studies indicated that mesenchymal stromal cells from bone marrow (bmMSC) differ in their osteogenic differentiation capacity compared to MSC from term placenta (pMSC). We extended these studies and investigated the expression of factors involved in regulation of bone metabolism in both cell types. To this end, MSC were expanded in vitro and characterized. The total transcriptome was investigated by microarrays, and for selected genes, the differences in gene expression were explored by quantitative reverse transcriptase-polymerase chain reaction, immunocytochemistry, and flow cytometry. We report that bmMSC and pMSC share expression of typical lineage surface markers, including CD73, CD90, CD105, and lack of CD14, CD34, and CD45. However, according to transcriptome analyses, they differ significantly in their expression of more than 590 genes. Factors involved in bone metabolism, including alkaline phosphatase (P<0.05), osteoglycin (P<0.05), osteomodulin (P<0.05), runt-related transcription factor 2 (Runx2) (P<0.04), and WISP2 (P<0.05), were expressed at significantly lower levels in pMSC, but twist-related protein 2 (Twist2) (P<0.0002) was expressed at significantly higher levels. The osteogenic differentiation capacity of pMSC was very low. The adipogenic differentiation was somewhat more prominent in bmMSC, while the chondrogenic differentiation seemed not to differ between bmMSC and pMSC, as determined by histochemical staining. However, expression and induction of peroxisome proliferator-activated receptor gamma-2 (PPAR?2) and Sox9, factors involved in early adipogenesis and chondrogenesis, respectively, were higher in bmMSC. We conclude that despite many similarities between bmMSC and pMSC, when expanded under identical conditions, they vary considerably with respect to their in vitro differentiation potential. For regenerative purposes, the choice of MSC may therefore influence the outcome of a treatment considerably. PMID:23763516

  19. Differential effects of pentylenetetrazol-kindling on long-term potentiation of population excitatory postsynaptic potentials and population spikes in the CA1 region of rat hippocampus.

    PubMed

    Palizvan, M R; Fathollahi, Y; Semnanian, S; Hajezadeh, S; Mirnajafizadh, J

    2001-04-13

    The effects of pentylenetetrazol-kindling on synaptic transmission and the effectiveness of ? pattern primed-bursts (PBs) for the induction of long-term potentiation (LTP) of population excitatory postsynaptic potentials and population spikes were investigated in hippocampal CA1 of pentylenetetrazol-kindled rats. Experiments were carried out in the control and kindled animals at two post-kindling periods, i.e., 48-144 h (early phase) and 30-33 days (long lasting phase). Field potentials (population excitatory postsynaptic potentials, pEPSPs; and population spikes, PSs) were recorded at the stratum radiatum and the stratum pyramidale following stimulation of the stratum fibers, respectively. PBs were delivered to stratum fibers and PB potentiation was assessed. The results showed that 48-144 h after kindling there was no significant difference for pEPSP slope and PS amplitude between two groups. But at 30-33 days after kindling, the pEPSP slope in the stratum radiatum of kindled animals decreased, whereas the amplitude of PSs increased compared to those of controls. Shortly after kindling, control animals had normal LTP of pEPSP slope and PS amplitude in response to PBs, but kindled rats lack LTP of pEPSP slope and PBs induced LTP of PS amplitude in most of kindled animals. In 30-33 days after kindling, PB potentiation was not observed in the stratum radiatum of kindled animals but PBs induced LTP of PS amplitude, which was significantly greater than that of control animals. The effect is compatible with the hypothesis, which postulates kindling-associated functional deficit in hippocampus, especially CA1, as an explanation for the behavioral deficits seen with the kindling model of epilepsy. PMID:11292451

  20. Ne--N/sub 2/ potential energy surface from high-resolution total differential scattering experiments and a close-coupling and infinite-order-sudden analysis

    SciTech Connect

    Beneventi, L.; Casavecchia, P.; Vecchiocattivi, F.; Volpi, G.G.; Lemoine, D.; Alexander, M.H.

    1988-09-15

    High-resolution crossed molecular beam measurements of the total differential cross section (DCS) for the scattering of Ne by N/sub 2/ at a collision energy of E = 75.8 meV are reported. Strongly quenched diffraction oscillations superimposed on the falloff of the main rainbow structure are clearly resolved. A reliable Ne--N/sub 2/ potential energy surface (PES) is derived by simultaneously fitting second virial, diffusion, and viscosity coefficient data taken from the literature. Information on the anisotropy of the interaction is obtained from the quenching of the diffraction oscillations in the total DCS within the framework of the infinite-order-sudden (IOS) approximation. The reliability of the IOS approximation in deriving a fully anisotropic potential energy surface from the measured scattering dynamics is examined and demonstrated by performing exact close-coupling calculations for the present experimental conditions and then comparing both integral and differential total and rotationally inelastic cross sections. The derived PES is compared with recently proposed theoretical model potential surfaces. Although in satisfactory agreement with bulk properties, none of these surfaces predicts correctly the present scattering data, each having significantly different spherical and/or anisotropic components in comparison with the PES derived here.

  1. Presence of Antigen-Experienced T Cells with Low Grade of Differentiation and Proliferative Potential in Chronic Chagas Disease Myocarditis

    PubMed Central

    Cabeza-Meckert, Patricia; Viotti, Rodolfo; Garelli, Fernando; Favaloro, Liliana E.; Favaloro, Roberto R.; Laguens, Rubén; Laucella, Susana A.

    2014-01-01

    Background The main consequence of chronic Trypanosoma cruzi infection is the development of myocarditis in approximately 20–30% of infected individuals but not until 10–20 years after the initial infection. We have previously shown that circulating interferon-?-secreting T cells responsive to Trypanosoma cruzi antigens in chronic Chagas disease patients display a low grade of differentiation and the frequency of these T lymphocytes decreases along with the severity of heart disease. This study thought to explore the expression of inhibitory receptors, transcription factors of type 1 or regulatory T cells, and markers of T cell differentiation, immunosenescence or active cell cycle in cardiac explants from patients with advanced Chagas disease myocarditis. Methodology/Principal Findings The expression of different markers for T and B cells as well as for macrophages was evaluated by immunohistochemistry and immunofluorescence techniques in cardiac explants from patients with advanced chronic Chagas disease submitted to heart transplantation. Most infiltrating cells displayed markers of antigen-experienced T cells (CD3+, CD4+, CD8+, CD45RO+) with a low grade of differentiation (CD27+, CD57?, CD45RA?, PD-1?). A skewed T helper1/T cytotoxic 1 profile was supported by the expression of T-bet; whereas FOXP3+ cells were scarce and located only in areas of severe myocarditis. In addition, a significant proliferative capacity of CD3+ T cells, assessed by Ki67 staining, was found. Conclusions/Significance The quality of T cell responses and immunoregulatory mechanisms might determine the pattern of the cellular response and the severity of disease in chronic Trypanosoma cruzi infection. PMID:25144227

  2. Gender depended potentiality of differentiation of human umbilical cord mesenchymal stem cells into oocyte-Like cells in vitro.

    PubMed

    Qiu, Pubin; Bai, Yaofu; Pan, Shaohui; Li, Wei; Liu, Weishuai; Hua, Jinlian

    2013-07-01

    Recent studies have demonstrated that germ-like cells could be differentiated from human umbilical cord mesenchymal stem cells (hUC-MSCs) in vitro. Whether the sexuality of hUC-MSCs affects the formation efficiency of germ-like cells derived from hUC-MSCs is still unclear. To clearly test the formation efficiency of oocyte-like cells from male and female hUC-MSCs, obtained hUC-MSCs were induced by 20% follicular fluid (FF) according to the method that has been proved by our previous studies. Results showed that hUC-MSCs differentiated into oocyte-like structures and expressed germ cell makers. It was noted that the presence of advanced oocyte-like cells in male hUC-MSCs (m-hUC-MSCs) was similar as that in female hUC-MSCs (f-hUC-MSCs); however, the expression of germ cell's specific markers in m-hUC-MSCs was delayed compared with that in f-hUC-MSCs. In addition, immunofluorescence analysis demonstrated that germ cell-specific markers, Oct4, Vasa, Dazl, ZP2, ZP3 and Stra8, were expressed on the 14th day after induction in both f-hUC-MSCs and m-hUC-MSCs. However, the size of oocyte-like cells from f-hUC-MSCs was larger than that in m-hUC-MSCs. The level of secreted oestradiol was significantly higher in f-hUC-MSCs than m-hUC-MSCs. We sought to determine whether critical germ cell's transcription factor-Figl? will promote the development of oocyte-like cells. Some germ cell-specific markers were increased when exogenous Figl? was transfected into hUC-MSCs. This process implied that germ-like cells might be produced by over-expression of exogenous germ cell-specific gene, and this process was similar as that in production of germ cells in induced pluripotent stem cells (iPSCs). Finally, to verify the feasibility that hUC-MSCs differentiate into germ cells, hUC-MSCs were transplanted into seminiferous tubules and kidney capsule of mouse, respectively, and we found the transplanted cells differentiated into germ-like cells in recipient's seminiferous tubules and kidney capsule. This study will provide a simple model to study mammalian germ cell specification using hUC-MSCs in vitro. PMID:23657870

  3. Identification of three microsatellites at the human myelin oligodendrocyte glycoprotein (MOG) locus, a gene potentially involved in multiple sclerosis

    SciTech Connect

    Borot, N.; Dolbois, L. [C.I.G.H.-C.N.R.S., Toulouse (France); Coppin, H. [U395 INSERM Purpan, Toulouse (France)] [and others

    1994-09-01

    The gene encoding MOG is located on the short arm of chromosome 6, less than 120 kb telomeric to HLA-F. We have cloned the MOG gene from a cosmid library. Using tandemly repeated dinucleotides, we probed the genomic region containing the human MOG gene in order to identify and localize polymorphic markers: three microsatellites were characterized in that region. Using a polymerase chain reaction-based technique, we studied length variability for these three markers among 173 healthy individuals and 167 multiple sclerosis patients. Heterozygosity varied from 50% to 60% according to the marker. Pairwise studies showed significant linkage disequilibrium between some alleles. Multiple sclerosis patients and controls were not shown to have statistically significant differences in the MOG region. Further studies on the coding regions are in progress in order to exclude any involvement of the MOG gene in multiple sclerosis.

  4. Toxin detection based on action potential shape analysis using a realistic mathematical model of differentiated NG108-15 cells

    PubMed Central

    Mohan, Dinesh K; Molnar, Peter; Hickman, James J.

    2010-01-01

    The NG108-15 neuroblastoma / glioma hybrid cell line has been frequently used for toxin detection, pharmaceutical screening and as a whole-cell biosensor. However, detailed analysis of its action potentials during toxin or drug administration has not been accomplished previously using patch clamp electrophysiology. In order to explore the possibility of identifying toxins based on their effect on the shape of intracellularly or extracellularly detected action potentials, we created a computer model of the action potential generation of this cell type. To generate the experimental data to validate the model, voltage dependent sodium, potassium and high-threshold calcium currents, as well as action potentials, were recorded from NG108-15 cells with conventional whole-cell patch-clamp methods. Based on the classic Hodgkin-Huxley formalism and the linear thermodynamic description of the rate constants, ion-channel parameters were estimated using an automatic fitting method. Utilizing the established parameters, action potentials were generated in the model and were optimized to represent the actual recorded action potentials to establish baseline conditions. To demonstrate the applicability of the method for toxin detection and discrimination, the effect of tetrodotoxin (a sodium channel blocker) and tefluthrin (a pyrethroid that is a sodium channel opener) were studied. The two toxins affected the shape of the action potentials differently and their respective effects were identified based on the changes in the fitted parameters. Our results represent one of the first steps to establish a complex model of NG108-15 cells for quantitative toxin detection based on action potential shape analysis of the experimental results. PMID:16460924

  5. Differential human multiple myeloma cell line responsiveness to interferon-alpha. Analysis of transcription factor activation and interleukin 6 receptor expression.

    PubMed Central

    Jelinek, D F; Aagaard-Tillery, K M; Arendt, B K; Arora, T; Tschumper, R C; Westendorf, J J

    1997-01-01

    Although IFN-alpha is commonly used as maintenance treatment for multiple myeloma patients, its effectiveness is varied. In this study, we have used a panel of IL-6 responsive myeloma cell lines that vary remarkably in responsiveness to IFN-alpha. Three cell lines were growth arrested by IFN-alpha; however, IFN-alpha significantly stimulated growth of the fourth cell line, KAS-6/1. Our studies have focused on elucidating the mechanism of differential IFN-alpha responsiveness. First, we have shown that IFN-alpha-stimulated growth of the KAS-6/1 cells did not result from induction of autocrine IL-6 expression. Second, analysis of Stats 1, 2, and 3 and IFN regulatory factor-1 (IRF-1) and IRF-2 activation failed to reveal differences between the IFN-alpha growth-arrested or growth-stimulated cells. Third, although IFN-alpha treatment of the IFN-alpha growth-inhibited cell lines reduced IL-6 receptor (IL-6R) expression, IFN-alpha also reduced KAS-6/1 IL-6R expression. Finally, although IFN-alpha treatment reduced IL-6R numbers on each cell line, analysis of Stat protein activation revealed that the receptors were still functional. We conclude that myeloma cell responsiveness to IFN-alpha is heterogeneous and that mechanisms of IFN-alpha-mediated growth inhibition other than IL-6R downregulation must exist in myeloma. Identification of these mechanisms may allow development of agents that are more universally effective than IFN-alpha. PMID:9022078

  6. Multiple Structurally Distinct ER? mRNA Variants in Zebrafish are Differentially Expressed by Tissue Type, Stage of Development and Estrogen Exposure

    PubMed Central

    Cotter, Kellie A.; Yershov, Anya; Novillo, Apolonia; Callard, Gloria V.

    2013-01-01

    It is well established that estrogen-like environmental chemicals interact with the ligand-binding site of estrogen receptors (ER) to disrupt transcriptional control of estrogen responsive targets. Here we investigate the possibility that estrogens also impact splicing decisions on estrogen responsive genes, such as that encoding ER? itself. Targeted PCR cloning was applied to identify six ER? mRNA variants in zebrafish. Sequencing revealed alternate use of transcription and translation start sites, multiple exon deletions, intron retention and alternate polyadenylation. As determined by quantitative (q)PCR, N-terminal mRNA variants predicting long (ER?L) and short (ER?S) isoforms were differentially expressed by tissue-type, sex, stage of development and estrogen exposure. Whereas ER?L mRNA was diffusely distributed in liver, brain, heart, eye, and gonads, ER?S mRNA was preferentially expressed in liver (female > male) and ovary. Neither ER?L nor ER?S transcripts varied significantly during development, but 17?-estradiol selectively increased accumulation of ER?S mRNA (~170-fold by 120 hpf), an effect mimicked by bisphenol-A and diethylstilbestrol. Significantly, a C-truncated variant (ER?S-Cx) lacking most of the ligand binding and AF-2 domains was transcribed exclusively from the short isoform promoter and was similar to ER?S in its tissue-, stage- and estrogen inducible expression. These results support the idea that promoter choice and alternative splicing of the esr1 gene of zebrafish are part of the autoregulatory mechanism by which estrogen modulates subsequent ER? expression, and further suggest that environmental estrogens could exert some of their toxic effects by altering the relative abundance of structurally and functionally distinct ER? isoforms. PMID:24090614

  7. Identification of differentially expressed genes potentially involved in the tolerance of Lotus tenuis to long-term alkaline stress.

    PubMed

    Paz, Rosalía Cristina; Rocco, Rubén Anibal; Jiménez-Bremont, Juan Francisco; Rodríguez-Kessler, Margarita; Becerra-Flora, Alicia; Menéndez, Ana Bernardina; Ruíz, Oscar Adolfo

    2014-09-01

    Soil alkalinity is one of the most serious agricultural problems limiting crop yields. The legume Lotus tenuis is an important forage acknowledged by its ability to naturally grow in alkaline soils. To gain insight into the molecular responses that are activated by alkalinity in L. tenuis plants, subtractive cDNA libraries were generated from leaves and roots of these plants. Total RNAs of non-stressed plants (pH 5.8; E.C. 1.2), and plants stressed by the addition of 10 mM of NaHCO3 (pH 9.0; E.C. 1.9), were used as source of the driver and the tester samples, respectively. RNA samples were collected after 14 and 28 days of treatment. A total of 158 unigenes from leaves and 92 unigenes from roots were obtained and classified into 11 functional categories. Unigenes from these categories (4 for leaves and 8 for roots), that were related with nutrient metabolism and oxidative stress relief were selected, and their differential expression analyzed by qRT-PCR. These genes were found to be differentially expressed in a time dependent manner in L. tenuis during the alkaline stress application. Data generated from this study will contribute to the understanding of the general molecular mechanisms associated to plant tolerance under long-term alkaline stress in plants. PMID:25025825

  8. X-ray fluorescence-based differentiation of neck tissues in a bovine model: implications for potential intraoperative use.

    PubMed

    Lahav, G; Shilstein, S; Shchemelinin, S; Ikher, S; Halperin, D; Chechik, R; Breskin, A

    2015-05-01

    This study explores the possibility of using X-ray fluorescence (XRF)-based trace-element analysis for differentiation of various bovine neck tissues. It is motivated by the requirement for an intra-operative in-vivo method for identifying parathyroid glands, particularly beneficial in surgery in the central neck-compartment. Using a dedicated X-ray spectral analysis, we examined ex-vivo XRF spectra from various histologically verified fresh neck tissues from cow, which was chosen as the animal model; these tissues included fat, muscle, thyroid, parathyroid, lymph nodes, thymus and salivary gland. The data for six trace elements K, Fe, Zn, Br, Rb and I, provided the basis for tissue identification by using multi-parameter analysis of the recorded XRF spectra. It is shown that the combination of XRF signals from these elements is sufficient for a reliable tissue differentiation. The average total abundance of these trace elements was evaluated in each tissue type, including parathyroid and salivary gland for the first time. It is shown that some tissues can unequivocally be identified on the basis of the abundance of a single element, for example, iodine and zinc for the identification of thyroid gland and muscle, respectively. PMID:25677045

  9. Native nucleus pulposus tissue matrix promotes notochordal differentiation of human induced pluripotent stem cells with potential for treating intervertebral disc degeneration.

    PubMed

    Liu, Yongxing; Fu, Susan; Rahaman, Mohamed N; Mao, Jeremy J; Bal, B Sonny

    2015-03-01

    Native porcine nucleus pulposus (NP) tissue harbors a number of notochordal cells (NCs). Whether the native NP matrix supports the homeostasis of notochordal cells is poorly understood. We hypothesized the NP matrix alone may contain sufficient regulatory factors and can serve as stimuli to generate notochordal cells (NCs) from human pluripotent stem cells. NCs are a promising cell sources for cell-based therapy to treat some types of intervertebral disc (IVD) degeneration. One major limitation of this emerging technique is the lack of available NCs as a potential therapeutic cell source. Human pluripotent stem cells derived from reprogramming or somatic cell nuclear transfer technique may yield stable and unlimited source for therapeutic use. We devised a new method to use porcine NP matrix to direct notochordal differentiation of human induced pluripotent stem cells (hiPSCs). The results showed that hiPSCs successfully differentiated into NC-like cells under the influence of devitalized porcine NP matrix. The NC-like cells expressed typical notochordal marker genes including brachyury (T), cytokeratin-8 (CK-8) and cytokeratin-18 (CK-18), and they displayed the ability to generate NP-like tissue in vitro, which was rich in aggrecan and collagen type II. These findings demonstrated the proof of concept for using native NP matrix to direct notochordal differentiation of hiPSCs. It provides a foundation for further understanding the biology of NCs, and eventually towards regenerative therapies for disc degeneration. PMID:24889905

  10. The DNA glycosylases OGG1 and NEIL3 influence differentiation potential, proliferation, and senescence-associated signs in neural stem cells

    SciTech Connect

    Reis, Amilcar [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)] [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden); Hermanson, Ola, E-mail: ola.hermanson@ki.se [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)] [Linnaeus Center in Developmental Biology for Regenerative Medicine (DBRM), Department of Neuroscience, Karolinska Institutet, SE 17177 Stockholm (Sweden)

    2012-07-13

    Highlights: Black-Right-Pointing-Pointer DNA glycosylases OGG1 and NEIL3 are required for neural stem cell state. Black-Right-Pointing-Pointer No effect on cell viability by OGG1 or NEIL3 knockdown in neural stem cells. Black-Right-Pointing-Pointer OGG1 or NEIL3 RNA knockdown result in decreased proliferation and differentiation. Black-Right-Pointing-Pointer Increased HP1{gamma} immunoreactivity after NEIL3 knockdown suggests premature senescence. -- Abstract: Embryonic neural stem cells (NSCs) exhibit self-renewal and multipotency as intrinsic characteristics that are key parameters for proper brain development. When cells are challenged by oxidative stress agents the resulting DNA lesions are repaired by DNA glycosylases through the base excision repair (BER) pathway as a means to maintain the fidelity of the genome, and thus, proper cellular characteristics. The functional roles for DNA glycosylases in NSCs have however remained largely unexplored. Here we demonstrate that RNA knockdown of the DNA glycosylases OGG1 and NEIL3 decreased NSC differentiation ability and resulted in decreased expression of both neuronal and astrocytic genes after mitogen withdrawal, as well as the stem cell marker Musashi-1. Furthermore, while cell survival remained unaffected, NEIL3 deficient cells displayed decreased cell proliferation rates along with an increase in HP1{gamma} immunoreactivity, a sign of premature senescence. Our results suggest that DNA glycosylases play multiple roles in governing essential neural stem cell characteristics.

  11. Comparative genomics of multiple strains of Pseudomonas cannabina pv. alisalensis, a potential model pathogen of both Monocots and Dicots

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Comparative genomics of closely related pathogens that differ in host range can provide insights into mechanisms of host-pathogen interactions and host adaptation. Sequencing multiple strains of the same pathogen further reveals information concerning pathogen diversity and the molecular basis of vi...

  12. Multiple techniques for mineral identification on Mars: a study of hydrothermal rocks as potential analogues for astrobiology sites on Mars

    Microsoft Academic Search

    Janice L. Bishop; Enver Murad; Rocco L. Mancinelli

    2004-01-01

    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

  13. CD34-expressing human thymocyte precursors proliferate in response to interleukin-7 but have lost myeloid differentiation potential.

    PubMed

    Schmitt, C; Ktorza, S; Sarun, S; Blanc, C; De Jong, R; Debre, P

    1993-12-15

    CD34 is a marker for pluripotent stem cells also present on lineage-committed hematopoietic progenitors from bone marrow and a subpopulation of immature thymocytes. To characterize these early immature thymocytes, we have studied 24 pediatric thymus samples for CD34/7 expression. Three subpopulations could be defined from these T-cell receptor (TcR-) immature thymocytes: CD34+7++ (12.0 +/- 5.8), CD34-7++ (12.6 +/- 8.6), and CD34-7+ (71.5 +/- 17.0%). CD7++ represents upregulation of this antigen and is expressed by cells of a blast-like morphology. Three-color flow cytometric analysis of these three subsets suggests the following ordered differentiation sequence: CD34+7++1-4-8-45RA+-->CD34+7++1+ 4+8-45RA+/- -->CD34-7++1+4+8-+45RO+-->CD34-7+1++4+8+45RO+. Early immature thymocyte cell division is essential in the thymus to generate a large number of precursors before the initiation of the selection process. We observed that both CD2 as well CD28 activation pathways were inefficient to serve as costimulant with phorbol ester 12-O-tetradecanoyl phorbol 13-acetate or interleukin-2 (IL-2) to induce the proliferation of the three CD34/7 subsets isolated by cell sorting. However, whereas IL-1, IL-2, IL-3, IL-4, granulocyte colony-stimulating factor, and granulocyte-macrophage colony-stimulating factor were ineffective, IL-7 was a potent cytokine, alone or in synergy with stem cell factor (SCF) to induce immature thymocyte proliferation. The proliferation induced by IL-7 or IL-7 + SCF is restricted to the CD34+ cells and, after 4 or 8 days of culture with IL-7, some CD34+7++ acquire the expression of CD4 and/or CD8, but remain CD3/TcR-. We also tested the myeloid differentiation capacity of these CD34 immature thymocytes. Using two different approaches, myeloid colony formation in methylcellulose and limiting dilution analysis in the presence of myeloid growth factors, we were unable to detect myeloid differentiation capacity from CD34+ early thymocytes, whereas CD34+7+ from bone marrow contained about 10% of the clonogenic cells present in the CD34+7- fraction. Together, these data support the concept that thymic CD34+7++ represents the earliest thymic subset of fully committed T-lineage cells, capable of proliferating specifically to IL-7. PMID:7505122

  14. The proliferation and tenogenic differentiation potential of bone marrow-derived mesenchymal stromal cell are influenced by specific uniaxial cyclic tensile loading conditions.

    PubMed

    Nam, Hui Yin; Pingguan-Murphy, Belinda; Amir Abbas, Azlina; Mahmood Merican, Azhar; Kamarul, Tunku

    2015-06-01

    It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue[Formula: see text] assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain [Formula: see text] 1 Hz was applied. However, at 8 % strain [Formula: see text] 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % [Formula: see text] 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs. PMID:25351891

  15. TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas.

    PubMed

    Avior, Yishai; Biancotti, Juan Carlos; Benvenisty, Nissim

    2015-06-01

    Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a scorecard representing tissues from all germ layers and extraembryonic tissues. TeratoScore, an online, open-source platform based on this scorecard, distinguishes pluripotent stem cell-derived teratomas from malignant tumors, translating cell potency into a quantitative measure (http://benvenisty.huji.ac.il/teratoscore.php). The teratomas used for the algorithm also allowed us to examine gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. Chromosomally aberrant teratomas show a significantly different gene expression signature from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, congruent with human chromosomal syndromes. PMID:26070610

  16. Cardiac side population cells have a potential to migrate and differentiate into cardiomyocytes in vitro and in vivo

    PubMed Central

    Oyama, Tomomi; Nagai, Toshio; Wada, Hiroshi; Naito, Atsuhiko Thomas; Matsuura, Katsuhisa; Iwanaga, Koji; Takahashi, Toshinao; Goto, Motohiro; Mikami, Yoko; Yasuda, Noritaka; Akazawa, Hiroshi; Uezumi, Akiyoshi; Takeda, Shin'ichi; Komuro, Issei

    2007-01-01

    Side population (SP) cells, which can be identified by their ability to exclude Hoechst 33342 dye, are one of the candidates for somatic stem cells. Although bone marrow SP cells are known to be long-term repopulating hematopoietic stem cells, there is little information about the characteristics of cardiac SP cells (CSPs). When cultured CSPs from neonatal rat hearts were treated with oxytocin or trichostatin A, some CSPs expressed cardiac-specific genes and proteins and showed spontaneous beating. When green fluorescent protein–positive CSPs were intravenously infused into adult rats, many more (?12-fold) CSPs were migrated and homed in injured heart than in normal heart. CSPs in injured heart differentiated into cardiomyocytes, endothelial cells, or smooth muscle cells (4.4%, 6.7%, and 29% of total CSP-derived cells, respectively). These results suggest that CSPs are intrinsic cardiac stem cells and involved in the regeneration of diseased hearts. PMID:17261849

  17. TeratoScore: Assessing the Differentiation Potential of Human Pluripotent Stem Cells by Quantitative Expression Analysis of Teratomas

    PubMed Central

    Avior, Yishai; Biancotti, Juan Carlos; Benvenisty, Nissim

    2015-01-01

    Summary Teratoma formation is the gold standard assay for testing the capacity of human pluripotent stem cells to differentiate into all embryonic germ layers. Although widely used, little effort has been made to transform this qualitative assay into a quantitative one. Using gene expression data from a wide variety of cells, we created a scorecard representing tissues from all germ layers and extraembryonic tissues. TeratoScore, an online, open-source platform based on this scorecard, distinguishes pluripotent stem cell-derived teratomas from malignant tumors, translating cell potency into a quantitative measure (http://benvenisty.huji.ac.il/teratoscore.php). The teratomas used for the algorithm also allowed us to examine gene expression differences between tumors with a diploid karyotype and those initiated by aneuploid cells. Chromosomally aberrant teratomas show a significantly different gene expression signature from that of teratomas originating from diploid cells, particularly in central nervous system-specific genes, congruent with human chromosomal syndromes. PMID:26070610

  18. Heteromeric Kv7.2/7.3 channels differentially regulate action potential initiation and conduction in neocortical myelinated axons.

    PubMed

    Battefeld, Arne; Tran, Baouyen T; Gavrilis, Jason; Cooper, Edward C; Kole, Maarten H P

    2014-03-01

    Rapid energy-efficient signaling along vertebrate axons is achieved through intricate subcellular arrangements of voltage-gated ion channels and myelination. One recently appreciated example is the tight colocalization of K(v)7 potassium channels and voltage-gated sodium (Na(v)) channels in the axonal initial segment and nodes of Ranvier. The local biophysical properties of these K(v)7 channels and the functional impact of colocalization with Na(v) channels remain poorly understood. Here, we quantitatively examined K(v)7 channels in myelinated axons of rat neocortical pyramidal neurons using high-resolution confocal imaging and patch-clamp recording. K(v)7.2 and 7.3 immunoreactivity steeply increased within the distal two-thirds of the axon initial segment and was mirrored by the conductance density estimates, which increased from ~12 (proximal) to 150 pS ?m(-2) (distal). The axonal initial segment and nodal M-currents were similar in voltage dependence and kinetics, carried by K(v)7.2/7.3 heterotetramers, 4% activated at the resting membrane potential and rapidly activated with single-exponential time constants (~15 ms at 28 mV). Experiments and computational modeling showed that while somatodendritic K(v)7 channels are strongly activated by the backpropagating action potential to attenuate the afterdepolarization and repetitive firing, axonal K(v)7 channels are minimally recruited by the forward-propagating action potential. Instead, in nodal domains K(v)7.2/7.3 channels were found to increase Na(v) channel availability and action potential amplitude by stabilizing the resting membrane potential. Thus, K(v)7 clustering near axonal Na(v) channels serves specific and context-dependent roles, both restraining initiation and enhancing conduction of the action potential. PMID:24599470

  19. Microbial Carriage State of Peripheral Blood Dendritic cells (DCs) in Chronic Periodontitis Influences DC Differentiation, Atherogenic Potential

    PubMed Central

    Carrion, Julio; Scisci, Elizabeth; Miles, Brodie; Sabino, Gregory J.; Zeituni, Amir E; Gu, Ying; Bear, Adam; Genco, Caroline A; Brown, David L.; Cutler, Christopher W

    2012-01-01

    The low grade oral infection chronic periodontitis (CP) has been implicated in coronary artery disease risk, but the mechanisms are unclear. Here, a pathophysiological role for blood dendritic cells (DCs) in systemic dissemination of oral mucosal pathogens to atherosclerotic plaques was investigated in humans. The frequency and microbiome of CD19?BDCA-1+DC-SIGN+ blood myeloid DCs (mDCs) were analyzed in CP subjects with, or without existing acute coronary syndrome (ACS) and in healthy controls (CTL). FACS analysis revealed a significant increase in blood mDCs in the following order: CTLdifferentiation of monocytes into immature mDCs; moreover, mDCs secreted high levels of MMP-9 and upregulated C1q, HSP60, HSP-70, CCR2 and CXCL16 transcripts in response to P. gingivalis in a fimbriae-dependent manner. Moreover, the survival of the anaerobe P. gingivalis under aerobic conditions was enhanced when within mDCs. Immunofluorescence analysis of oral mucosa and atherosclerotic plaques demonstrate infiltration with mDCs, colocalized with P. gingivalis. Our results suggest a role for blood mDCs in harboring and disseminating pathogens from oral mucosa to atherosclerosis plaques, which may provide key signals for mDC differentiation and atherogenic conversion. PMID:22891282

  20. Cytokine and chemokine profiles in fibromyalgia, rheumatoid arthritis and systemic lupus erythematosus: a potentially useful tool in differential diagnosis.

    PubMed

    Wallace, Daniel J; Gavin, Igor M; Karpenko, Oleksly; Barkhordar, Farnaz; Gillis, Bruce S

    2015-06-01

    Making a correct diagnosis is pivotal in the practice of clinical rheumatology. Occasionally, the consultation fails to provide desired clarity in making labeling an individual as having fibromyalgia (FM), systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA). A chemokine and cytokine multiplex assay was developed and tested with the goal of improving and achieving an accurate differential diagnosis. 160 patients with FM, 98 with RA and 100 with SLE fulfilling accepted criteria were recruited and compared to 119 controls. Supernatant cytokine concentrations for IL-6, IL-8, MIP-1 alpha and MIP-1 beta were determined using the Luminex multiplex immunoassay bead array technology after mitogenic stimulation of cultured peripheral blood mononuclear cells. Each patient's profile was scored using a logistical regression model to achieve statistically determined weighting for each chemokine and cytokine. Among the 477 patients evaluated, the mean scores for FM (1.7 ± 1.2; 1.52-1.89), controls (-3.56 ± 5.7; -4.59 to -2.54), RA (-0.68 ± 2.26; -1.12 to -0.23) and SLE (-1.45 ± 3.34, -2.1 to -0.79). Ninety-three percent with FM scored positive compared to only 11 % of healthy controls, 69 % RA or 71 % SLE patients had negative scores. The sensitivity, specificity, positive predictive and negative predictive value for having FM compared to controls was 93, 89, 92 and 91 %, respectively (p < 2.2 × 10(-16)). Evaluating cytokine and chemokine profiles in stimulated cells reveals patterns that are uniquely present in patients with FM. This assay can be a useful tool in assisting clinicians in differentiating systemic inflammatory autoimmune processes from FM and its related syndromes and healthy individuals. PMID:25377646

  1. Multiple types of Na + currents mediate action potential electrogenesis in small neurons of mouse dorsal root ganglia

    Microsoft Academic Search

    Tomoya Matsutomi; Chizumi Nakamoto; Taixing Zheng; Jun-ichi Kakimura; Nobukuni Ogata

    2006-01-01

    Small (+ channel subtypes, two of which being resistant to tetrodotoxin (TTX). Each subtype mediates Na+ current with distinct kinetic property. However, it is not known how each type of Na+ channel contributes to the generation of action potentials in small DRG neurons. Therefore, we investigated the correlation between Na+ currents in voltage-clamp recordings and corresponding action potentials in current-clamp

  2. The calculus of the electric potential and field intensity in multiple electrodes lateral tunneling transistors with double gate

    E-print Network

    Sever Spanulescu

    2009-12-15

    The paper presents an adaptive over-relaxation method for calculating the electric potential and field intensity, for a complex tunnel transistor structure involving a split gate and a shielding boundary. The accuracy and speed of the method has been numerically tested and found satisfactory for the study of such devices by calculating the tunneling currents for the obtained potential distribution.

  3. Asymptotic behavior of the potential and existence of a periodic solution for a second order differential equation

    Microsoft Academic Search

    Alfonso Castro; Chen Chang

    2003-01-01

    We establish the existence of a 2?-periodic solution for a second order semilinear equation in terms of the asymptotic behavior of the potential of the nonlinearity. Our condition includes the case in which the nonlinearity is asymptotically linear with slopes at infinity of the jumping nonlinearity between the positive axes and the first Fucik spectrum curve (see [S. Fucik (1976).

  4. Differential localization of brain systems subserving memory for names and faces in normal subjects with event-related potentials

    Microsoft Academic Search

    Werner Sommer; Esther Komoss; Stefan R. Schweinberger

    1997-01-01

    Evidence from brain-damaged patients suggests different memory systems for verbal and nonverbal stimuli which also have different neuroanatomical substrates. We explored whether the scalp topographies of event-related potentials (ERPs) might confirm the dissociability of these systems. Unfamiliar faces and names were presented in separate conditions, study blocks alternating with recognition blocks. During recognition the familiarity of each stimulus was rated

  5. Visualization of space competition and plume formation with complex potentials for multiple source flows: Some examples and novel application to Chao lava flow (Chile)

    NASA Astrophysics Data System (ADS)

    Weijermars, R.

    2014-03-01

    Fluid displacement in a continuum pressured by a variable constellation of source flows can be visualized as solutions of line integrals. The algorithms are based on complex potentials that provide exact solutions of the Navier-Stokes equation and allow users to specify both the location and flux strength of multiple sources. If relative strength and positioning of the sources are varied, a wide range of flow patterns and particle paths can be traced. Time-dependent variations in the strength of the sources can account for transient-flow problems. A further expansion is superposition of a background flow, which displaces the particle paths issued from the sources into concentrated plumes. The outlined modeling technique for visualization of multiple plume displacements is potentially relevant for a wide spectrum of practical situations. Detailed applications are possible, such as time tracking of groundwater-plume migration from a series of pollution sources, tracking of salt-feeder-stock flow and suture zone formation when salt issued from the stocks coalesces into a salt canopy, and designing of optimal spacing and relative pressure strength of multiple water injection wells in field-development plans for hydrocarbon production. Further applications are highlighted in the main text, including a simulation of geometrical features exposed in the Chao coulee (Chilean Andes).

  6. Differentiating Event-Related Potential Components Sensitive to Emotion in Middle Childhood: Evidence from Temporal-Spatial PCA

    PubMed Central

    Kujawa, Autumn; Weinberg, Anna; Hajcak, Greg; Klein, Daniel N.

    2012-01-01

    Event-related potentials (ERPs) may be particularly useful for examining emotional processing across development. Though a number of ERP components are sensitive to emotional content in adults, previous studies have yet to systematically examine the components sensitive to emotion in children. The current study used temporal-spatial principal components analysis (PCA) to identify ERP components in response to complex emotional images in nine-year-old children. Three components were modulated by emotional content and were similar to those previously observed in adults, including: the early posterior negativity, the P300, and a sustained relative positivity similar to the late positive potential (LPP). Compared to those previously observed in adults, the components sensitive to emotion in children were maximal over more occipital regions and the LPP component appeared to be less protracted in time, perhaps indicative of less elaborative processing of emotional stimuli. PMID:22692816

  7. Event-related brain potentials elicited by rhyming and non-rhyming pictures differentiate subgroups of reading disabled adolescents

    Microsoft Academic Search

    W. Brian McPherson; Peggy T. Ackerman; D. Michael Oglesby; ROSCOE A. DYKlVIAN

    1996-01-01

    Event-related brain potentials were recorded while disabled adolescent subjects read and judged whether two sequentially presented\\u000a pictures had names that rhymed. Subjects with relatively good phonetic skills displayed an N400 priming effect, i.e., a significant\\u000a reduction in the amplitude of the negative peak, occurring approximately 400 msec post-stimulus, for pictures with names that\\u000a rhymed with preceding pictures as compared with

  8. Differentiation potential of conditionally immortalized mesenchymal progenitor cells from adult marrow of a H-2Kb-tsA58 transgenic mouse.

    PubMed

    Dennis, J E; Caplan, A I

    1996-06-01

    Primary cultures were initiated from marrow, spleen, and bone explants of an adult H-2Kb-tsA58 transgenic mouse (immortomouse). All cultures were initiated in immortalizing conditions, and an additional marrow culture was first incubated for 1 week in standard conditions and then switched to immortalizing conditions. Marrow cells immediately immortalized were designated the marrow immediate population (MIP); those immortalized after 1 week were termed the marrow delayed population (MDP). MIP and MDP cells both contained a mixture of fibroblastic or flattened cells, and the MIP cells contained an additional subpopulation of adipocytic (Oil Red-O positive) cells. Alkaline phosphatase expression was induced by dexamethasone (10(-7) M) in MDP cells while MIP, spleen, and bone explant cells had only a low level of expression. MDP and MIP cells differentiated into bone when combined with porous calcium phosphate ceramics and implanted subcutaneously into nude mice while bone- and spleen-derived cells did not. Clones were isolated from the MDP and MIP cell populations and tested for differentiated phenotypes. Some MIP-derived clones exhibited adipocytic characteristics while MDP-derived subclones were negative. Histologic examination of porous ceramic implanted clones showed that all of the clones had osteogenic potential. Clones exposed to either dexamethasone, human recombinant bone morphogenetic protein-2, or horse serum plus hydrocortisone showed differences in expression of adipocytic or osteogenic markers. These immortalized cultures have retained both adipocytic and osteogenic potential even after 1 year of continuous culture, and provide a model system for clonal analysis of the developmental potential of marrow-derived mesenchymal precursor cells. PMID:8655606

  9. Differential Expression of Long Noncoding RNAs in Human Cumulus Cells Related to Embryo Developmental Potential: A Microarray Analysis.

    PubMed

    Xu, Xiao-Feng; Li, Juan; Cao, Yun-Xia; Chen, Da-Wei; Zhang, Zhi-Guo; He, Xiao-Jin; Ji, Dong-Mei; Chen, Bei-Li

    2015-06-01

    Long noncoding RNAs (lncRNAs), which are prevalently transcribed in the genome, are involved in a variety of biological functions, yet little is known about their abundance in human cumulus cells (CCs) during oocyte development. Here, we describe the expression profile of lncRNAs in 3 pairs of cumulus cells from mature oocytes that result in high-quality embryo (H-CCs) and from oocytes that result in poor-quality embryo (P-CCs) using microarray analysis. In this study, a total of 20 563 lncRNAs were expressed in human CCs. One hundred and twenty four lncRNAs were consistently upregulated, and 509 lncRNAs were consistently downregulated in all samples analyzed (fold change ? 2.0, P < .05). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate 5 upregulated and 7 downregulated lncRNAs. The qRT-PCR results in the study were confirmed to be consistent with the microarray results. Network analysis was used for further research. The results displayed the differentially expressed lncRNAs in P-CCs between H-CCs, which suggested that lncRNAs may contribute to the processes of oocyte and early embryo development. PMID:25527423

  10. Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation

    Microsoft Academic Search

    C. S. Potter; R L Peterson; J L Barth; N D Pruett; D F Jacobs; M J Kern; W S Argraves; J P Sundberg; A Awgulewitsch

    2006-01-01

    It is increasingly evident that the molecular mechanisms underlying hair follicle differentiation and cycling recapitulate principles of embryonic patterning and organ regeneration. Here we used Hoxc13-overexpressing transgenic mice (also known as GC13 mice), known to develop severe hair growth defects and alopecia, as a tool for defining pathways of hair follicle differentiation. Gene array analysis performed with RNA from postnatal

  11. Evaluation of a Gas Chromatograph-Differential Mobility Spectrometer for Potential Water Monitoring on the International Space Station

    NASA Technical Reports Server (NTRS)

    Wallace, William T.; Limero, Thomas F.; Gazda, Daniel B.; Macatangay, Ariel V.; Dwivedi, Prabha; Fernandez, Facundo M.

    2015-01-01

    Environmental monitoring for manned spaceflight has long depended on archival sampling, which was sufficient for short missions. However, the longer mission durations aboard the International Space Station (ISS) have shown that enhanced, real-time monitoring capabilities are necessary in order to protect both the crewmembers and the spacecraft systems. Over the past several years, a number of real-time environmental monitors have been deployed on the ISS. Currently, volatile organic compounds (VOCs) in the station air are monitored by the Air Quality Monitor (AQM), a small, lightweight gas chromatograph-differential mobility spectrometer. For water monitoring, real-time monitors are used for total organic carbon (TOC) and biocide analysis. No information on the actual makeup of the TOC is provided presently, however. An improvement to the current state of environmental monitoring could be realized by modifying a single instrument to analyze both air and water. As the AQM currently provides quantitative, compound-specific information for VOCs in air samples, this instrument provides a logical starting point to evaluate the feasibility of this approach. The major hurdle for this effort lies in the liberation of the target analytes from the water matrix. In this presentation, we will discuss our recent studies, in which an electro-thermal vaporization unit has been interfaced with the AQM to analyze target VOCs at the concentrations at which they are routinely detected in archival water samples from the ISS. We will compare the results of these studies with those obtained from the instrumentation routinely used to analyze archival water samples.

  12. Differential interactions of antiretroviral agents with LXR, ER and GR nuclear receptors: potential contributing factors to adverse events

    PubMed Central

    Svärd, J; Blanco, F; Nevin, D; Fayne, D; Mulcahy, F; Hennessy, M; Spiers, J P

    2014-01-01

    Background and Purpose:?Antiretroviral (ARV) drugs activate pregnane X receptors and constitutive androstane receptors, increasing the risk of drug interactions due to altered drug metabolism and disposition. The closely related liver X receptors (LXR?/?), oestrogen receptors (ER?/?) and glucocorticoid receptor (GR) regulate many endogenous processes such as lipid/cholesterol homeostasis, cellular differentiation and inflammation. However, ARV drug activation of these nuclear receptors has not been thoroughly investigated. Experimental Approach:?The ability of an ARV drug library to activate LXR?/?, ER?/? and GR was assessed using a combined in silico and in vitro approach encompassing computational docking and molecular descriptor filtering, cell-free time-resolved fluorescence resonance energy transfer co-activator assays to assess direct binding to ligand-binding domains (LBDs), cell-based reporter assays and target gene expression. Key Results:?Direct LBD interactions with LXR? and/or LXR? were predicted in silico and confirmed in vitro for darunavir, efavirenz, flavopiridol, maraviroc and tipranavir. Likewise, efavirenz was also predicted and confirmed as a ligand of ER?-LBD. Interestingly, atazanavir and ritonavir also activated LXR?/? in reporter assays, while tipranavir enhanced transcriptional activity of ER?. Effects on ER and LXR target gene expression were confirmed for efavirenz and tipranavir. Conclusions and Implications:?There was good agreement between in silico predictions and in vitro results. However, some nuclear receptor interactions identified in vitro were probably due to allosteric effects or nuclear receptor cross-talk, rather than direct LBD binding. This study indicates that some of the adverse effects associated with ARV use may be mediated through ‘off-target’ effects involving nuclear receptor activation. PMID:24372550

  13. Laser-structured bacterial nanocellulose hydrogels support ingrowth and differentiation of chondrocytes and show potential as cartilage implants.

    PubMed

    Ahrem, Hannes; Pretzel, David; Endres, Michaela; Conrad, Daniel; Courseau, Julien; Müller, Hartmut; Jaeger, Raimund; Kaps, Christian; Klemm, Dieter O; Kinne, Raimund W

    2014-03-01

    The small size and heterogeneity of the pores in bacterial nanocellulose (BNC) hydrogels limit the ingrowth of cells and their use as tissue-engineered implant materials. The use of placeholders during BNC biosynthesis or post-processing steps such as (touch-free) laser perforation can overcome this limitation. Since three-dimensionally arranged channels may be required for homogeneous and functional seeding, three-dimensional (3-D) laser perforation of never-dried BNC hydrogels was performed. Never-dried BNC hydrogels were produced in different shapes by: (i) the cultivation of Gluconacetobacter xylinus (DSM 14666; synonym Komagataeibacter xylinus) in nutrient medium; (ii) the removal of bacterial residues/media components (0.1M NaOH; 30 min; 100 °C) and repeated washing (deionized water; pH 5.8); (iii) the unidirectional or 3-D laser perforation and cutting (pulsed CO2 Rofin SC × 10 laser; 220 ?m channel diameter); and (iv) the final autoclaving (2M NaOH; 121 °C; 20 min) and washing (pyrogen-free water). In comparison to unmodified BNC, unidirectionally perforated--and particularly 3-D-perforated - BNC allowed ingrowth into and movement of vital bovine/human chondrocytes throughout the BNC nanofiber network. Laser perforation caused limited structural modifications (i.e. fiber or globular aggregates), but no chemical modifications, as indicated by Fourier transform infrared spectroscopy, X-ray photoelectron scattering and viability tests. Pre-cultured human chondrocytes seeding the surface/channels of laser-perforated BNC expressed cartilage-specific matrix products, indicating chondrocyte differentiation. 3-D-perforated BNC showed compressive strength comparable to that of unmodified samples. Unidirectionally or 3-D-perforated BNC shows high biocompatibility and provides short diffusion distances for nutrients and extracellular matrix components. Also, the resulting channels support migration into the BNC, matrix production and phenotypic stabilization of chondrocytes. It may thus be suitable for in vivo application, e.g. as a cartilage replacement material. PMID:24334147

  14. POTENTIAL USE OF RECOMBINANT HUMAN THYROTROPIN IN THE TREATMENT OF DISTANT METASTASES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER

    PubMed Central

    Klubo-Guriezdzinska, Joanna; Burman, Kenneth D.; Van Nostrand, Douglas; Mete, Mihriye; Jonklaas, Jacqueline; Wartofsky, Leonard

    2014-01-01

    Objective In order to effectively treat differentiated thyroid cancer (DTC) with radioiodine (RAI) it is necessary to raise serum TSH levels either endogenously by thyroid hormone withdrawal (THW) or exogenously by administration of recombinant human TSH (rhTSH). The goal of this review is to present current data on the relative efficacy and side effects profile of rhTSH-aided versus THW-aided RAI therapy for the treatment of patients with distant metastases of DTC. Methods We have searched the PubMed database for articles including the keywords “rhTSH”, “thyroid cancer”, and “distant metastases” published between January 1, 1996 and January 7, 2012. As references, we used clinical case series, case reports, review articles, and practical guidelines. Results Exogenous stimulation of TSH is associated with better quality of life because it obviates signs and symptoms of hypothyroidism resulting from endogenous TSH stimulation. The rate of neurological complications after rhTSH and THW-aided RAI therapy for brain and spine metastases is similar. The rate of leukopenia, thrombocytopenia, xerostomia, and pulmonary fibrosis is similar after preparation for RAI treatment with rhTSH and THW. There is currently a controversy regarding RAI uptake in metastatic lesions after preparation with rhTSH versus THW, with some studies suggesting equal and some superior uptake after preparation with THW. Analysis of available retrospective studies comparing survival rates, progression free survival, and biochemical and structural response to a dosimetrically-deterrnined dose of RAI shows similar efficacy after preparation for therapy with rhTSH and THW. Conclusion The rhTSH stimulation is not presently approved by the FDA as a method of preparation for adjunctive therapy with RAI in patients with metastatic DTC. Data on rhTSH compassionate use suggest that rhTSH stimulation is as equally effective as THW as a method of preparation for dosimetry-based RAI treatment in patients with RAI-avid metastatic DTC. PMID:23186979

  15. Does size difference in allogeneic cancellous bone granules loaded with differentiated autologous cultured osteoblasts affect osteogenic potential?

    PubMed

    Lee, Sang-Uk; Chung, Yang-Guk; Kim, Seok-Jung; Oh, Il-Hoan; Kim, Yong-Sik; Ju, Sung-Hun

    2014-02-01

    We study the efficacy of bone regeneration by using two differently sized allogeneic cancellous bone granules loaded with autologous cultured osteoblasts in a rabbit model. Critical-sized bone defects of the radial shaft were made in 40 New Zealand White rabbits. Small allogeneic bone granules (150-300 ?m in diameter) loaded with cultured differentiated autologous osteoblasts were implanted into one forearm (SBG group) and large bone granules (500-710 ?m) loaded with osteoblasts were implanted into the forearm of the other side (LBG group). Radiographic evaluations were performed at 3, 6, 9 and 12 weeks and histology and micro-CT image analysis were carried out at 6 and 12 weeks post-implantation. On radiographic evaluation, the LBG group showed a higher bone quantity index at 3 and 6 weeks post-implantation (P < 0.05) but statistical significance was lost at 9 and 12 weeks. The progression of biological processes of the SBG group was faster than that of the LBG group. On micro-CT image analysis, the LBG group revealed a higher total bone volume and surface area than the SBG group at 6 weeks (P < 0.05) but the difference decreased at 12 weeks and was without statistical significance. Histological evaluation also revealed faster progression of new bone formation and maturation in the SBG group. Thus, the two differently sized allogeneic bone granules loaded with co-cultured autologous osteoblasts show no differences in the amount of bone regeneration, although the SBG group exhibits faster progression of bone regeneration and remodeling. This method might therefore provide benefits, such as a short healing time and easy application in an injectable form, in a clinical setting. PMID:24346683

  16. Potential for Measurement of Trace Volatile Organic Compounds in Closed Environments Using Gas Chromatograph/Differential Mobility Spectrometer

    NASA Technical Reports Server (NTRS)

    Limero, Thomas; Cheng, Patti

    2007-01-01

    For nearly 3.5 years, the Volatile Organic Analyzer (VOA) has routinely analyzed the International Space Station (ISS) atmosphere for a target list of approximately 20 volatile organic compounds (VOCs). Additionally, an early prototype of the VOA collected data aboard submarines in two separate trials. Comparison of the data collected on ISS and submarines showed a surprising similarity in the atmospheres of the two environments. Furthermore, in both cases it was demonstrated that the VOA data can detect hardware issues unrelated to crew health. Finally, it was also clear in both operations that the VOA s size and resource consumption were major disadvantages that would restrict its use in the future. The VOA showed the value of measuring VOCs in closed environments, but it had to be shrunk if it was to be considered for future operations in these environments that are characterized by cramped spaces and limited resources. The Sionex Microanalyzer is a fraction of the VOA s size and this instrument seems capable of maintaining or improving upon the analytical performance of the VOA. The two design improvements that led to a smaller, less complex instrument are the Microanalyzer s use of recirculated air as the gas chromatograph s carrier gas and a micromachined detector. Although the VOA s ion mobility spectrometer and the Microanalyzer s differential mobility spectrometer (DMS) are related detector technologies, the DMS was more amenable to micromachining. This paper will present data from the initial assessment of the Microanalyzer. The instrument was challenged with mixtures that simulated the VOCs typically detected in closed-environment atmospheres.

  17. Evaluation of differentiated neurotherapy programs for a patient after severe TBI and long term coma using event-related potentials

    PubMed Central

    Pachalska, Maria; ?ukowicz, Ma?gorzata; Kropotov, Juri D.; Herman-Sucharska, Izabela; Talar, Jan

    2011-01-01

    Summary Background This article examines the effectiveness of differentiated rehabilitation programs for a patient with frontal syndrome after severe TBI and long-term coma. We hypothesized that there would be a small response to relative beta training, and a good response to rTMS, applied to regulate the dynamics of brain function. Case Report M. L-S, age 26, suffered from anosognosia, executive dysfunction, and behavioral changes, after a skiing accident and prolonged coma, rendering him unable to function independently in many situations of everyday life. Only slight progress was made after traditional rehabilitation. The patient took part in 20 sessions of relative beta training (program A) and later in 20 sessions of rTMS (program B); both programs were combined with behavioral training. We used standardized neuropsychological testing, as well as ERPs before the experiment, after the completion of program A, and again after the completion of program B. As hypothesized, patient M.L-S showed small improvements in executive dysfunction and behavioral disorders after the conclusion of program A, and major improvement after program B. Similarly, in physiological changes the patient showed small improvement after relative beta training and a significant improvement of the P300 NOGO component after the rTMS program. Conclusions The rTMS program produced larger physiological and behavioral changes than did relative beta training. A combination of different neurotherapeutical approaches (such as neurofeedback, rTMS, tDCS) can be suggested for similar severe cases of TBI. ERPs can be used to assess functional brain changes induced by neurotherapeutical programs. PMID:21959618

  18. Nitric oxide determines mesodermic differentiation of mouse embryonic stem cells by activating class IIa histone deacetylases: potential therapeutic implications in a mouse model of hindlimb ischemia.

    PubMed

    Spallotta, Francesco; Rosati, Jessica; Straino, Stefania; Nanni, Simona; Grasselli, Annalisa; Ambrosino, Valeria; Rotili, Dante; Valente, Sergio; Farsetti, Antonella; Mai, Antonello; Capogrossi, Maurizio C; Gaetano, Carlo; Illi, Barbara

    2010-03-31

    In human endothelial cells, nitric oxide (NO) results in class IIa histone deacetylases (HDACs) activation and marked histone deacetylation. It is unknown whether similar epigenetic events occur in embryonic stem cells (ESC) exposed to NO and how this treatment could influence ESC therapeutic potential during tissue regeneration.This study reports that the NO-dependent class IIa HDACs subcellular localization and activity decreases the global acetylation level of H3 histones in ESC and that this phenomenon is associated with the inhibition of Oct4, Nanog, and KLF4 expression. Further, a NO-induced formation of macromolecular complexes including HDAC3, 4, 7, and protein phosphatase 2A (PP2A) have been detected. These processes correlated with the expression of the mesodermal-specific protein brachyury (Bry) and the appearance of several vascular and skeletal muscle differentiation markers. These events were abolished by the class IIa-specific inhibitor MC1568 and by HDAC4 or HDAC7 short interfering RNA (siRNA). The ability of NO to induce mesodermic/cardiovascular gene expression prompted us to evaluate the regenerative potential of these cells in a mouse model of hindlimb ischemia. We found that NO-treated ESCs injected into the cardiac left ventricle selectively localized in the ischemic hindlimb and contributed to the regeneration of muscular and vascular structures. These findings establish a key role for NO and class IIa HDACs modulation in ESC mesodermal commitment and enhanced regenerative potential in vivo. PMID:20073046

  19. A Novel Strategy to Increase the Proliferative Potential of Adult Human ?-Cells While Maintaining Their Differentiated Phenotype

    PubMed Central

    Aly, Haytham; Rohatgi, Nidhi; Marshall, Connie A.; Grossenheider, Tiffani C.; Miyoshi, Hiroyuki; Stappenbeck, Thaddeus S.; Matkovich, Scot J.; McDaniel, Michael L.

    2013-01-01

    Our previous studies demonstrated that Wnt/GSK-3/?-catenin and mTOR signaling are necessary to stimulate proliferative processes in adult human ?-cells. Direct inhibition of GSK-3, that engages Wnt signaling downstream of the Wnt receptor, increases ?-catenin nuclear translocation and ?-cell proliferation but results in lower insulin content. Our current goal was to engage canonical and non-canonical Wnt signaling at the receptor level to significantly increase human ?-cell proliferation while maintaining a ?-cell phenotype in intact islets. We adopted a system that utilized conditioned medium from L cells that expressed Wnt3a, R-spondin-3 and Noggin (L-WRN conditioned medium). In addition we used a ROCK inhibitor (Y-27632) and SB-431542 (that results in RhoA inhibition) in these cultures. Treatment of intact human islets with L-WRN conditioned medium plus inhibitors significantly increased DNA synthesis ?6 fold in a rapamycin-sensitive manner. Moreover, this treatment strikingly increased human ?-cell proliferation ?20 fold above glucose alone. Only the combination of L-WRN conditioned medium with RhoA/ROCK inhibitors resulted in substantial proliferation. Transcriptome-wide gene expression profiling demonstrated that L-WRN medium provoked robust changes in several signaling families, including enhanced ?-catenin-mediated and ?-cell-specific gene expression. This treatment also increased expression of Nr4a2 and Irs2 and resulted in phosphorylation of Akt. Importantly, glucose-stimulated insulin secretion and content were not downregulated by L-WRN medium treatment. Our data demonstrate that engaging Wnt signaling at the receptor level by this method leads to necessary crosstalk between multiple signaling pathways including activation of Akt, mTOR, Wnt/?-catenin, PKA/CREB, and inhibition of RhoA/ROCK that substantially increase human ?-cell proliferation while maintaining the ?-cell phenotype. PMID:23776620

  20. Clinical and pathologic differential diagnosis of selected potential bioterrorism agents of interest to pediatric health care providers.

    PubMed

    Stocker, J Thomas

    2006-06-01

    The early recognition of potential bioterrorism agents has been of increasing concern in recent years. The Centers for Disease Control and Prevention has categorized and listed biological terrorism agents. Although any or all of the highest risk biological agents (including inhalation anthrax, pneumonic plague, smallpox, tularemia, botulism, and viral hemorrhagic fevers) can be seen in the pediatric patient, several agents might closely resemble--at least in their initial stages-some of the more common childhood illnesses. The awareness of these similarities and, more importantly,their differences, are critical for all health care professionals. Selected examples of some typical childhood illnesses are presented and then compared with three of the most virulent biological agents (smallpox, anthrax and plague) that might be used in a bioterrorism attack. PMID:16815456

  1. Identification of potential pharmacological and toxicological targets differentiating structural analogs by a combination of transcriptional profiling and promoter analysis in LS-180 and Caco-2 adenocarcinoma cell lines.

    PubMed

    Hartley, Dylan P; Dai, Xudong; Yabut, Jocelyn; Chu, Xiaoyan; Cheng, Olivia; Zhang, Theresa; He, Yudong D; Roberts, Chris; Ulrich, Roger; Evers, Raymond; Evans, David C

    2006-08-01

    Detecting and understanding the potential for off-target pharmacological effects is critical in the optimization of lead compounds in drug discovery programs. Compound-mediated activation of the pregnane X receptor (PXR; NR1I2), a key regulator for drug metabolism genes, is often monitored to avoid potential drug-drug interactions. Two structural analogs, MRL-1 and MRL-2, were determined to be equivalent PXR activators in trans-activation assays. To differentiate these two PXR activators, their transcriptional effects were examined in PXR-sufficient (LS180) and PXR-deficient (Caco-2) adenocarcinoma cell lines. Both compounds regulated drug-management genes (e.g. CYP3A4, CYP2B6, UGT1A1 and ABCB1) in LS180 cells, but not in PXR-deficient Caco-2 cells. The potency of MRL-1 and MRL-2 on PXR activation was again equivalent as revealed by a set of 113 genes that were regulated by four prototypical PXR agonists (rifampicin, ritonavir, troglitazone and dexamethasone) in the LS180 cells. The specificity of the PXR signature genes was supported by the enrichment of putative PXR binding sites uncovered by sequence-based promoter analyses. Interestingly, an additional off-target activity of MRL-2 was suggested where sterol response element binding protein binding sites were found enriched in a subset of PXR signature genes. These genes, involved in cholesterol and fatty acid synthesis, were significantly regulated by ritonavir, chlorpromazine and MRL-2, which were linked to the manifestation of phospholipidosis. The present study demonstrates the utility of our approach in the differentiation and selection of lead compounds for drug development. PMID:16847427

  2. An In Vitro Expansion System for Generation of Human iPS Cell-Derived Hepatic Progenitor-Like Cells Exhibiting a Bipotent Differentiation Potential

    PubMed Central

    Yanagida, Ayaka; Ito, Keiichi; Chikada, Hiromi; Nakauchi, Hiromitsu; Kamiya, Akihide

    2013-01-01

    Hepatoblasts, hepatic stem/progenitor cells in liver development, have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In regenerative medicine and drug screening for the treatment of severe liver diseases, human induced pluripotent stem (iPS) cell-derived mature functional hepatocytes are considered to be a potentially good cell source. However, induction of proliferation of these cells is difficult ex vivo. To circumvent this problem, we generated hepatic progenitor-like cells from human iPS cells using serial cytokine treatments in vitro. Highly proliferative hepatic progenitor-like cells were purified by fluorescence-activated cell sorting using antibodies against CD13 and CD133 that are known cell surface markers of hepatic stem/progenitor cells in fetal and adult mouse livers. When the purified CD13highCD133+ cells were cultured at a low density with feeder cells in the presence of suitable growth factors and signaling inhibitors (ALK inhibitor A-83-01 and ROCK inhibitor Y-27632), individual cells gave rise to relatively large colonies. These colonies consisted of two types of cells expressing hepatocytic marker genes (hepatocyte nuclear factor 4? and ?-fetoprotein) and a cholangiocytic marker gene (cytokeratin 7), and continued to proliferate over long periods of time. In a spheroid formation assay, these cells were found to express genes required for mature liver function, such as cytochrome P450 enzymes, and secrete albumin. When these cells were cultured in a suitable extracellular matrix gel, they eventually formed a cholangiocytic cyst-like structure with epithelial polarity, suggesting that human iPS cell-derived hepatic progenitor-like cells have a bipotent differentiation ability. Collectively these data indicate that this novel procedure using an in vitro expansion system is useful for not only liver regeneration but also for the determination of molecular mechanisms that regulate liver development. PMID:23935837

  3. An in vitro expansion system for generation of human iPS cell-derived hepatic progenitor-like cells exhibiting a bipotent differentiation potential.

    PubMed

    Yanagida, Ayaka; Ito, Keiichi; Chikada, Hiromi; Nakauchi, Hiromitsu; Kamiya, Akihide

    2013-01-01

    Hepatoblasts, hepatic stem/progenitor cells in liver development, have a high proliferative potential and the ability to differentiate into both hepatocytes and cholangiocytes. In regenerative medicine and drug screening for the treatment of severe liver diseases, human induced pluripotent stem (iPS) cell-derived mature functional hepatocytes are considered to be a potentially good cell source. However, induction of proliferation of these cells is difficult ex vivo. To circumvent this problem, we generated hepatic progenitor-like cells from human iPS cells using serial cytokine treatments in vitro. Highly proliferative hepatic progenitor-like cells were purified by fluorescence-activated cell sorting using antibodies against CD13 and CD133 that are known cell surface markers of hepatic stem/progenitor cells in fetal and adult mouse livers. When the purified CD13(high)CD133(+) cells were cultured at a low density with feeder cells in the presence of suitable growth factors and signaling inhibitors (ALK inhibitor A-83-01 and ROCK inhibitor Y-27632), individual cells gave rise to relatively large colonies. These colonies consisted of two types of cells expressing hepatocytic marker genes (hepatocyte nuclear factor 4? and ?-fetoprotein) and a cholangiocytic marker gene (cytokeratin 7), and continued to proliferate over long periods of time. In a spheroid formation assay, these cells were found to express genes required for mature liver function, such as cytochrome P450 enzymes, and secrete albumin. When these cells were cultured in a suitable extracellular matrix gel, they eventually formed a cholangiocytic cyst-like structure with epithelial polarity, suggesting that human iPS cell-derived hepatic progenitor-like cells have a bipotent differentiation ability. Collectively these data indicate that this novel procedure using an in vitro expansion system is useful for not only liver regeneration but also for the determination of molecular mechanisms that regulate liver development. PMID:23935837

  4. Platelet-rich plasma greatly potentiates insulin-induced adipogenic differentiation of human adipose-derived stem cells through a serine/threonine kinase Akt-dependent mechanism and promotes clinical fat graft maintenance.

    PubMed

    Cervelli, Valerio; Scioli, Maria G; Gentile, Pietro; Doldo, Elena; Bonanno, Elena; Spagnoli, Luigi G; Orlandi, Augusto

    2012-03-01

    The potential plasticity and therapeutic utility in tissue regeneration of human adipose-derived stem cells (ASCs) isolated from adult adipose tissue have recently been highlighted. The use of autologous platelet-rich plasma (PRP) represents an alternative strategy in regenerative medicine for the local release of multiple endogenous growth factors. Here we investigated the signaling pathways and effects of PRP and human recombinant insulin on proliferation and adipogenic differentiation of ASCs in vitro. PRP stimulated proliferation (EC(50) = 15.3 ± 1.3% vol/vol), whereas insulin's effect was the opposite (IC(50) = 3.0 ± 0.5 ?M). Although PRP alone did not increase adipogenesis, in association with insulin it prevented ASC proliferative arrest, greatly enhanced intracytoplasmic lipid accumulation, strongly increased serine/threonine kinase Akt phosphorylation and mouse monoclonal anti-sterol regulatory element binding protein-1 accumulation, and downregulated Erk-1 activity; adipogenic effects were markedly prevented by the Akt inhibitor wortmannin. PRP with insulin synergistically upregulated fibroblast growth factor receptor (FGFR) and downregulated epidermal growth factor receptor (ErbB) expression; moreover, PRP in association prevented insulin-induced insulin-like growth factor-1 receptor and insulin receptor downregulation. The inhibition of FGFR-1, epidermal growth factor receptor (EGFR), and epidermal growth factor receptor-2 (ErbB2) activity reduced ASC proliferation, but only that of FGFR-1 reduced adipogenesis and Akt phosphorylation, whereas the ErbB2 inhibition effects were the opposite. However, EGFR activity was needed for ErbB2-mediated inhibition of ASC adipogenesis. Clinically, the injection of insulin further ameliorated patients' 1-year PRP-induced fat graft volume maintenance and contour restoring. Our results ascertain that PRP in association with insulin greatly potentiates adipogenesis in human ASCs through a FGFR-1 and ErbB2-regulated Akt mechanism. The ameliorated clinical fat graft maintenance suggests additional useful translational applications of combined PRP-insulin treatment in regenerative medicine. PMID:23197780

  5. Memory Effects of Ion-Selective Electrodes: Theory and Computer Simulation of the Time-Dependent Potential Response to Multiple Sample Changes

    PubMed Central

    Morf, Werner E.; Pretsch, Ernö; de Rooij, Nicolaas F.

    2010-01-01

    A straightforward theoretical description of the time-dependent response of ion-selective membrane electrodes to multiple sample changes is presented. The derivation makes use of an approximation for the ion fluxes in the membrane, and of the superposition of partial fluxes induced by the step-changes. The general theory allows for any number of samples and ions. It is applied for the analysis of memory effects that reflect the influence of preceding samples on subsequent measurements. Various phenomena are discussed, including super-, near-, or sub-nernstian responses, shifts of apparent reference potentials, and potential dips with domains of reversed slopes. The theoretical results agree well with virtual experiments based on computer simulation. PMID:20376292

  6. Daratumumab and its potential in the treatment of multiple myeloma: overview of the preclinical and clinical development

    PubMed Central

    Phipps, Colin; Chen, Yunxin; Gopalakrishnan, Sathish

    2015-01-01

    Despite the recent major advancement in therapy for multiple myeloma, it remains an incurable disease. There remains an unmet need for novel therapies that target different mechanisms of action. Immunotherapy with monoclonal antibodies is a promising area of development and will expand our therapeutic armamentarium in the fight against myeloma. Daratumumab is a novel, high-affinity, therapeutic human monoclonal antibody against unique CD38 epitope with broad-spectrum killing activity. It has a favorable safety profile as monotherapy in patients with relapsed/refractory myeloma and also demonstrates significant single-agent activity. Abundant preclinical data supports its use in combination therapy and clinical studies on various exciting combinations are underway. This review focuses on the CD38 antigen and its targeting with daratumumab and provides an update on the results of recent clinical studies involving daratumumab.

  7. Evaluation of the effects of different culture media on the myogenic differentiation potential of adipose tissue- or bone marrow-derived human mesenchymal stem cells.

    PubMed

    Stern-Straeter, Jens; Bonaterra, Gabriel Alejandro; Juritz, Stephanie; Birk, Richard; Goessler, Ulrich Reinhart; Bieback, Karen; Bugert, Peter; Schultz, Johannes; Hörmann, Karl; Kinscherf, Ralf; Faber, Anne

    2014-01-01

    The creation of functional muscles/muscle tissue from human stem cells is a major goal of skeletal muscle tissue engineering. Mesenchymal stem cells (MSCs) from fat/adipose tissue (AT-MSCs), as well as bone marrow (BM-MSCs) have been shown to bear myogenic potential, which makes them candidate stem cells for skeletal muscle tissue engineering applications. The aim of this study was to analyse the myogenic differentiation potential of human AT-MSCs and BM-MSCs cultured in six different cell culture media containing different mixtures of growth factors. The following cell culture media were used in our experiments: mesenchymal stem cell growth medium (MSCGM)™ as growth medium, MSCGM + 5-azacytidine (5-Aza), skeletal muscle myoblast cell growth medium (SkGM)-2 BulletKit™, and 5, 30 and 50% conditioned cell culture media, i.e., supernatant of human satellite cell cultures after three days in cell culture mixed with MSCGM. Following the incubation of human AT-MSCs or BM-MSCs for 0, 4, 8, 11, 16 or 21 days with each of the cell culture media, cell proliferation was measured using the alamarBlue® assay. Myogenic differentiation was evaluated by quantitative gene expression analyses, using quantitative RT-PCR (qRT-PCR) and immunocytochemical staining (ICC), using well-defined skeletal markers, such as desmin (DES), myogenic factor 5 (MYF5), myosin, heavy chain 8, skeletal muscle, perinatal (MYH8), myosin, heavy chain 1, skeletal muscle, adult (MYH1) and skeletal muscle actin-?1 (ACTA1). The highest proliferation rates were observed in the AT-MSCs and BM-MSCs cultured with SkGM-2 BulletKit medium. The average proliferation rate was higher in the AT-MSCs than in the BM-MSCs, taking all six culture media into account. qRT-PCR revealed the expression levels of the myogenic markers, ACTA1, MYH1 and MYH8, in the AT-MSC cell cultures, but not in the BM-MSC cultures. The muscle-specific intermediate filament, DES, was only detected (by ICC) in the AT-MSCs, but not in the BM-MSCs. The strongest DES expression was observed using the 30% conditioned cell culture medium. The detection of myogenic markers using different cell culture media as stimuli was only achieved in the AT-MSCs, but not in the BM-MSCs. The strongest myogenic differentiation, in terms of the markers examined, was induced by the 30% conditioned cell culture medium. PMID:24220225

  8. Differential expression of transforming growth factor-beta in benign vs. papillary thyroid cancer nodules; a potential diagnostic tool?

    PubMed Central

    2014-01-01

    Background Thyroid nodules are common, but only 5% of nodules are found to be malignant. In North America, the incidence of thyroid cancer is increasing. Fine needle aspirate (FNA) biopsy is the diagnostic test of choice. Unfortunately, up to 20% of FNAs are non-diagnostic. A specific molecular marker for thyroid cancer is desirable. Evidence suggests that cell signaling through transforming growth factor beta (TGF- ?) is important in the development of thyroid cancer. We sought to compare the expression of TGF- ? in malignant and benign thyroid nodules. Methods From 2008-present, thyroid nodule tissue from thyroidectomy specimens was prospectively collected and stored at ?80°C. RNA extraction and reverse transcription was performed on 47 samples (24 papillary thyroid cancer and 23 benign nodules). Quantitative PCR using SYBR green was performed to detect TGF-?-1 and ?2. Resulting CT values were normalized against ?-actin. Gene expression was calculated using the 2-?CT method. Results A significantly greater expression of TGF- ?1 (p?potential diagnostic marker for papillary thyroid cancer. PMID:25927212

  9. Differential effects and potential adverse outcomes of ionic silver and silver nanoparticles in vivo and in vitro.

    PubMed

    Garcia-Reyero, Natŕlia; Kennedy, Alan J; Escalon, B Lynn; Habib, Tanwir; Laird, Jennifer G; Rawat, Arun; Wiseman, Steven; Hecker, Markus; Denslow, Nancy; Steevens, Jeffery A; Perkins, Edward J

    2014-04-15

    Nanoparticles are of concern because of widespread use, but it is unclear if metal nanoparticles cause effects directly or indirectly. We explored whether polyvinylpyrrolidone-coated silver nanoparticles (PVP-AgNPs) cause effects through intact nanoparticles or dissolved silver. Females of the model species fathead minnow (Pimephales promelas) were exposed to either 4.8 ?g/L of AgNO3 or 61.4 ?g/L of PVP-AgNPs for 96h. Microarray analyses were used to identify impacted receptors and toxicity pathways in liver and brain tissues that were confirmed using in vitro mammalian assays. AgNO3 and PVP-AgNP exposed fish had common and distinct effects consistent with both intact nanoparticles and dissolved silver causing effects. PVP-AgNPs and AgNO3 both affected pathways involved in Na(+), K(+), and H(+) homeostasis and oxidative stress but different neurotoxicity pathways. In vivo effects were supported by PVP-AgNP activation of five in vitro nuclear receptor assays and inhibition of ligand binding to the dopamine receptor. AgNO3 inhibited ligand binding to adrenergic receptors ?1 and ?2 and cannabinoid receptor CB1, but had no effect in nuclear receptor assays. PVP-AgNPs have the potential to cause effects both through intact nanoparticles and metal ions, each interacting with different initiating events. Since the in vitro and in vivo assays examined here are commonly used in human and ecological hazard screening, this work suggests that environmental health assessments should consider effects of intact nanoparticles in addition to dissolved metals. PMID:24684273

  10. Comparative analysis of various electrostatic potentials on docking precision against cyclin-dependent kinase 2 protein: a multiple docking approach.

    PubMed

    Tripathi, Sunil K; Soundarya, Rajendran Naga; Singh, Poonam; Singh, Sanjeev K

    2015-02-01

    The fundamental of molecular modeling is the interaction and binding to form a complex, because it explains the action of most drugs to a receptor active site. In the present study, different semiempirical (RM1, AM1, PM3, MNDO) and ab initio (HF, DFT) charge models were investigated for their performance in prediction of docking pose against CDK2 proteins with their respective inhibitor. Further, multiple docking approaches and Prime/MM-GBSA calculations were applied to predict the binding mode with respective charge model against CDK2 inhibitors. A reliable docking result was obtained using RRD, which showed significance improvement on ligand binding poses and docking score accuracy to the IFD. The combined use of RRD and Prime/MM-GBSA method could give a high correlation between the predicted binding free energy and experimental biological activity. The preliminary results point out that AM1 could be a precious charge model for design of new drugs with enhanced success rate. As a very similar result was also found for a different system of the protein-ligand binding, the suggested scoring function based on AM1 method seems to be applicable in drug design. The results from this study can provide insights into highest success rate for design of potent and selective CDK2 inhibitors. PMID:24923208

  11. Myeloid differentiation primary response gene 88-leukotriene B4 receptor 2 cascade mediates lipopolysaccharide-potentiated invasiveness of breast cancer cells

    PubMed Central

    Park, Geun-Soo; Kim, Jae-Hong

    2015-01-01

    Inflammation and local inflammatory mediators are inextricably linked to tumor progression through complex pathways in the tumor microenvironment. Lipopolysaccharide (LPS) exposure to tumor cells has been suggested to promote tumor invasiveness and metastasis. However, the detailed signaling mechanism involved has not been elucidated. In this study, we showed that LPS upregulated the expression of leukotriene B4 receptor-2 (BLT2) and the synthesis of BLT2 ligands in MDA-MB-231 and MDA-MB-435 breast cancer cells, thereby promoting invasiveness. BLT2 depletion with siRNA clearly attenuated LPS-induced invasiveness. In addition, we demonstrated that myeloid differentiation primary response gene 88 (MyD88) lies upstream of BLT2 in LPS-potentiated invasiveness and that this ‘MyD88-BLT2’ cascade mediates activation of NF-?B and the synthesis of IL-6 and IL-8, which are critical for the invasiveness and aggression of breast cancer cells. LPS-driven metastasis of MDA-MB-231 cells was also markedly suppressed by the inhibition of BLT2. Together, our results demonstrate, for the first time, that LPS potentiates the invasiveness and metastasis of breast cancer cells via a ‘MyD88-BLT2’-linked signaling cascade. PMID:25691060

  12. Th9 cells: differentiation and disease

    PubMed Central

    Kaplan, Mark H.

    2014-01-01

    Summary CD4+ T-helper cells regulate immunity and inflammation through the acquisition of potential to secrete specific cytokines. The acquisition of cytokine-secreting potential, in a process termed T-helper cell differentiation, is a response to multiple environmental signals including the cytokine milieu. The most recently defined subset of T-helper cells are termed Th9 and are identified by the potent production of interleukin-9 (IL-9). Given the pleiotropic functions of IL-9, Th9 cells might be involved in pathogen immunity and immune-mediated disease. In this review, I focus on recent developments in understanding the signals that promote Th9 differentiation, the transcription factors that regulate IL-9 expression, and finally the potential roles for Th9 cells in immunity in vivo. PMID:23405898

  13. Insights into information contained in multiplicative scatter correction parameters and the potential for estimating particle size from these parameters.

    PubMed

    Chen, Yi-Chieh; Thennadil, Suresh N

    2012-10-01

    This paper investigates the nature of information contained in scatter correction parameters. The study had two objectives. The first objective was to examine the nature and extent of information contained in scatter correction parameters. The second objective is to examine whether this information can be effectively extracted by proposing a method to obtain particularly the mean particle diameter from the scatter correction parameters. By using a combination of experimental data and simulated data generated using fundamental light propagation theory, a deeper and more fundamental insight of what information is removed by the multiplicative scatter correction (MSC) method is obtained. It was found that the MSC parameters are strongly influenced not only by particle size but also by particle concentration as well as refractive index of the medium. The possibility of extracting particle size information in addition to particle concentration was considered by proposing a two-step method which was tested using a 2-component and 4-component data set. This method can in principle, be used in conjunction with any scatter correction technique provided that the scatter correction parameters exhibit a systematic dependence with respect to particle size and concentration. It was found that the approach which uses the MSC parameters gave a better estimate of the particle diameter compared to using partial least squares (PLS) regression for the 2-component data. For the 4 component data it was found that PLS regression gave better results but further examination indicated this was due to chance correlations of the particle diameter with the two of the absorbing species in the mixture. PMID:22975178

  14. An evidence-based review of ixazomib citrate and its potential in the treatment of newly diagnosed multiple myeloma

    PubMed Central

    Offidani, Massimo; Corvatta, Laura; Caraffa, Patrizia; Gentili, Silvia; Maracci, Laura; Leoni, Pietro

    2014-01-01

    Proteasome inhibition represents one of the more important therapeutic targets in the treatment of multiple myeloma (MM), since by suppressing nuclear factor-?B activity, which promotes myelomagenesis, it makes plasma cells susceptible to proapoptotic signals. Bortezomib, the first proteasome inhibitor approved for MM therapy, has been shown to increase response rate and improve outcome in patients with relapsed/refractory disease and in the frontline setting, particularly when combined with immunomodulatory drugs and alkylating agents. Among second-generation proteasome inhibitors, ixazomib (MLN9708) is the first oral compound to be evaluated for the treatment of MM. Ixazomib has shown improved pharmacokinetic and pharmacodynamic parameters compared with bortezomib, in addition to similar efficacy in the control of myeloma growth and prevention of bone loss. Ixazomib was found to overcome bortezomib resistance and to trigger synergistic antimyeloma activity with dexamethasone, lenalidomide, and histone deacetylase inhibitors. Phase I/II studies using ixazomib weekly or twice weekly in relapsed/refractory MM patients suggested antitumor activity of the single agent, but more promising results have been obtained with the combination of ixazomib, lenalidomide, and dexamethasone in newly diagnosed MM. Ixazomib has also been used in systemic amyloidosis as a single agent, showing important activity in this difficult-to-treat plasma-cell dyscrasia. More frequent side effects observed during administration of ixazomib were thrombocytopenia, nausea, vomiting, diarrhea, fatigue, and rash, whereas severe peripheral neuropathy was rare. Here, we review the chemical characteristics of ixazomib, as well as its mechanism of action and results from preclinical and clinical trials. PMID:25302026

  15. Ion mobility mass spectrometry as a potential tool to assign disulfide bonds arrangements in peptides with multiple disulfide bridges.

    PubMed

    Echterbille, Julien; Quinton, Loďc; Gilles, Nicolas; De Pauw, Edwin

    2013-05-01

    Disulfide bridges play a major role in defining the structural properties of peptides and proteins. However, the determination of the cysteine pairing is still challenging. Peptide sequences are usually achieved using tandem mass spectrometry (MS/MS) spectra of the totally reduced unfolded species, but the cysteine pairing information is lost. On the other hand, MS/MS experiments performed on native folded species show complex spectra composed of nonclassical ions. MS/MS alone does not allow either the cysteine pairing or the full sequence of an unknown peptide to be determined. The major goal of this work is to set up a strategy for the full structural characterization of peptides including disulfide bridges annotation in the sequence. This strategy was developed by combining ion mobility spectrometry (IMS) and collision-induced dissociation (CID). It is assumed that the opening of one S-S bridge in a peptide leads to a structural evolution which results in a modification of IMS drift time. In the presence of multiple S-S bridges, the shift in arrival time will depend on which disulfide(s) has (have) been reduced and on the shape adopted by the generated species. Due to specific fragmentations observed for each species, CID experiments performed after the mobility separation could provide not only information on peptide sequence but also on the localization of the disulfide bridges. To achieve this goal, synthetic peptides containing two disulfides were studied. The openings of the bridges were carried out following different experimental conditions such as reduction, reduction/alkylation, or oxidation. Due to disulfide scrambling highlighted with the reduction approaches, oxidation of S-S bonds into cysteic acids appeared to be the best strategy. Cysteine connectivity was then unambiguously determined for the two peptides, without any disulfide scrambling interference. PMID:23509902

  16. Acibenzolar-s-methyl-induced resistance to Japanese pear scab is associated with potentiation of multiple defense responses.

    PubMed

    Faize, Mohamed; Faize, Lydia; Koike, Nobuyo; Ishizaka, Masumi; Ishii, Hideo

    2004-06-01

    ABSTRACT This study reports the mode of action of acibenzolar-S-methyl (ASM) against Japanese pear scab, caused by Venturia nashicola. Pretreatment of potted Japanese pear trees with ASM reduced scab symptoms and potentiated several lines of plant defense response. This included transcripts encoding polygalacturonase-inhibiting protein (PGIP) that were highly and transiently promoted after scab inoculation of plants pretreated with ASM, suggesting a possible role for defenses involved in direct interaction with the pathogen. The activity of the key enzyme of phenylpropanoid pathway, phenylalanine ammonia lyase (PAL), was enhanced in scab-inoculated leaves pretreated with ASM only 7 days after inoculation, suggesting that it may play a minor role in induced resistance. In this work, salicylic acid (SA) accumulation was enhanced in ASM-treated leaves for the first time, according to an equivalent time course to that of PAL activity. However, a delayed induction of SA accumulation in ASM-treated leaves compared with kinetics of induction of several pathogenesis- related (PR) proteins or their encoding genes suggested that resistance triggered by ASM may be SA-independent. Among these PR proteins, PR-1, chitinase and PR-10 were promoted early by ASM after scab inoculation. Peroxidase, as well as enzymes involved in the oxidative burst such as superoxide dismutase, catalase, and ascorbate peroxidase were weakly activated with ASM treatment alone or pathogen inoculation alone and highly enhanced in ASM pretreated plants upon challenge inoculation, suggesting the occurrence of priming phenomenon during the interaction of Japanese pear-ASM-V. nashicola. An early potentiation of the activity of these enzymes after scab inoculation of leaves pretreated with ASM suggested that active oxygen species may be involved as a signal for the activation of PR proteins or genes. PMID:18943485

  17. Glial Progenitor-Like Phenotype in Low-Grade Glioma and Enhanced CD133-Expression and Neuronal Lineage Differentiation Potential in High-Grade Glioma

    PubMed Central

    Rebetz, Johan; Tian, Dongping; Persson, Annette; Widegren, Bengt; Salford, Leif G.; Englund, Elisabet; Gisselsson, David; Fan, Xiaolong

    2008-01-01

    Background While neurosphere- as well as xenograft tumor-initiating cells have been identified in gliomas, the resemblance between glioma cells and neural stem/progenitor cells as well as the prognostic value of stem/progenitor cell marker expression in glioma are poorly clarified. Methodology/Principal Findings Viable glioma cells were characterized for surface marker expression along the glial genesis hierarchy. Six low-grade and 17 high-grade glioma specimens were flow-cytometrically analyzed for markers characteristics of stem cells (CD133); glial progenitors (PDGFR?, A2B5, O4, and CD44); and late oligodendrocyte progenitors (O1). In parallel, the expression of glial fibrillary acidic protein (GFAP), synaptophysin and neuron-specific enolase (NSE) was immunohistochemically analyzed in fixed tissue specimens. Irrespective of the grade and morphological diagnosis of gliomas, glioma cells concomitantly expressed PDGFR?, A2B5, O4, CD44 and GFAP. In contrast, O1 was weakly expressed in all low-grade and the majority of high-grade glioma specimens analyzed. Co-expression of neuronal markers was observed in all high-grade, but not low-grade, glioma specimens analyzed. The rare CD133 expressing cells in low-grade glioma specimens typically co-expressed vessel endothelial marker CD31. In contrast, distinct CD133 expression profiles in up to 90% of CD45-negative glioma cells were observed in 12 of the 17 high-grade glioma specimens and the majority of these CD133 expressing cells were CD31 negative. The CD133 expression correlates inversely with length of patient survival. Surprisingly, cytogenetic analysis showed that gliomas contained normal and abnormal cell karyotypes with hitherto indistinguishable phenotype. Conclusions/Significance This study constitutes an important step towards clarification of lineage commitment and differentiation blockage of glioma cells. Our data suggest that glioma cells may resemble expansion of glial lineage progenitor cells with compromised differentiation capacity downstream of A2B5 and O4 expression. The concurrent expression of neuronal markers demonstrates that high-grade glioma cells are endowed with multi-lineage differentiation potential in vivo. Importantly, enhanced CD133 expression marks a poor prognosis in gliomas. PMID:18398462

  18. Multiple Stressors in a Top Predator Seabird: Potential Ecological Consequences of Environmental Contaminants, Population Health and Breeding Conditions

    PubMed Central

    Bustnes, Jan O.; Bourgeon, Sophie; Leat, Eliza H. K.; Magnusdóttir, Ellen; Strřm, Hallvard; Hanssen, Sveinn A.; Petersen, Aevar; Olafsdóttir, Kristin; Borgĺ, Katrine; Gabrielsen, Geir W.; Furness, Robert W.

    2015-01-01

    Environmental contaminants may have impacts on reproduction and survival in wildlife populations suffering from multiple stressors. This study examined whether adverse effects of persistent organic pollutants (POPs) increased with poor population health and breeding conditions in three colonies (60–74°N) of great skua (Stercorarius skua) in the north-eastern Atlantic (Shetland, Iceland and Bjřrnřya [Bear Island]). POPs (organochlorines [OCs] and polybrominated diphenyl ethers [BDEs]) were measured in plasma of incubating birds (n = 222), concentrations differing nearly tenfold among colonies: Bjřrnřya (2009) > Bjřrnřya (2010) > Iceland (2009) > Shetland (2009). Reproductive success (hatching success and chick survival) showed that breeding conditions were favourable in Shetland and at Bjřrnřya (2010), but were very poor in Iceland and at Bjřrnřya (2009). Biomarkers indicated that health was poor in the Shetland population compared to the other populations. Females whose chicks hatched late had high POP concentrations in all colonies except at Bjřrnřya (2010), and females losing their eggs at Bjřrnřya (2009) tended to have higher concentrations than those hatching. Moreover, there was a negative relationship between female POP concentrations and chick body condition at hatching in Iceland and at Bjřrnřya (2010). Supplementary feeding experiments were conducted, and in Iceland where feeding conditions were poor, significant negative relationships were found between female POP concentrations and daily growth-rate in first-hatched chicks of control nests, but not in food supplemented nests. This suggests that negative impacts of POPs were mitigated by improved feeding conditions. For second-chicks, there was a strong negative relationship between the female POP concentrations and growth-rate, but no effects of supplementary feeding. Lowered adult return-rate between breeding seasons with increasing POP loads were found both at Bjřrnřya (2009) and in Shetland, especially related to BDEs. This indicates stronger fitness consequences of POPs following seasons with very poor breeding conditions and/or high reproductive effort. This study suggests that the impacts of POPs may differ depending on population health and breeding conditions, and that even low concentrations of POPs could have ecological consequences during adverse circumstances. This is important with regard to risk assessment of biomagnifying contaminants in marine ecosystems. PMID:26172383

  19. Net electron-phonon scattering rates in InN/GaN multiple quantum wells: The effects of an energy dependent acoustic deformation potential

    SciTech Connect

    Xia, H., E-mail: h.xia@unsw.edu.au; Patterson, R.; Feng, Y.; Shrestha, S.; Conibeer, G. [School of Photovoltaics and Renewable Energy Engineering, The University of New South Wales, Sydney, NSW 2052 (Australia)

    2014-08-11

    The rates of charge carrier relaxation by phonon emission are of substantial importance in the field of hot carrier solar cell, primarily in investigation of mechanisms to slow down hot carrier cooling. In this work, energy and momentum resolved deformation potentials relevant to electron-phonon scattering are computed for wurtzite InN and GaN as well as an InN/GaN multiple quantum well (MQW) superlattice using ab-initio methods. These deformation potentials reveal important features such as discontinuities across the electronic bandgap of the materials and variations over tens of eV. The energy dependence of the deformation potential is found to be very similar for wurtzite nitrides despite differences between the In and Ga pseudopotentials and their corresponding electronic band structures. Charge carrier relaxation by this mechanism is expected to be minimal for electrons within a few eV of the conduction band edge. However, hole scattering at energies more accessible to excitation by solar radiation is possible between heavy and light hole states. Moderate reductions in overall scattering rates are observed in MQW relative to the bulk nitride materials.

  20. Depression and Multiple Sclerosis

    MedlinePLUS

    ... various forms is common during the course of multiple sclerosis. In fact, studies have suggested that clinical depression, ... is easy to understand how a diagnosis of multiple sclerosis, a chronic condition with the potential for progressing ...

  1. Tissue loss (white syndrome) in the coral Montipora capitata is a dynamic disease with multiple host responses and potential causes

    PubMed Central

    Work, Thierry M.; Russell, Robin; Aeby, Greta S.

    2012-01-01

    Tissue loss diseases or white syndromes (WS) are some of the most important coral diseases because they result in significant colony mortality and morbidity, threatening dominant Acroporidae in the Caribbean and Pacific. The causes of WS remain elusive in part because few have examined affected corals at the cellular level. We studied the cellular changes associated with WS over time in a dominant Hawaiian coral, Montipora capitata, and showed that: (i) WS has rapidly progressing (acute) phases mainly associated with ciliates or slowly progressing (chronic) phases mainly associated with helminths or chimeric parasites; (ii) these phases interchanged and waxed and waned; (iii) WS could be a systemic disease associated with chimeric parasitism or a localized disease associated with helminths or ciliates; (iv) corals responded to ciliates mainly with necrosis and to helminths or chimeric parasites with wound repair; (v) mixed infections were uncommon; and (vi) other than cyanobacteria, prokaryotes associated with cell death were not seen. Recognizing potential agents associated with disease at the cellular level and the host response to those agents offers a logical deductive rationale to further explore the role of such agents in the pathogenesis of WS in M. capitata and helps explain manifestation of gross lesions. This approach has broad applicability to the study of the pathogenesis of coral diseases in the field and under experimental settings. PMID:22951746

  2. So that's what you meant! Event-related potentials reveal multiple aspects of context use during construction of message-level meaning.

    PubMed

    Wlotko, Edward W; Federmeier, Kara D

    2012-08-01

    Factors that modulate the influence of contextual information on semantic processing in language comprehension have been thoroughly investigated with the N400 component of the event-related potential (ERP), a direct measure of initial contact with semantic memory. Although context has a strong and immediate impact on processing, multiple mechanisms contribute to the construction of message-level representations during normal comprehension. Some of these may be engaged after or concurrent with the formation of an initial meaning representation, and can then serve to revise or reshape meaning. In this study, ERPs were recorded while participants read plausible sentences that continuously varied in the amount of contextual constraint for the sentence-final word, defined via extensive norming data including the range of possible alternative completions for the contexts. Consistent with numerous past studies, the amplitude of the N400 was graded with expectancy, as amplitudes decreased with increasing constraint. Additionally, a left-lateralized, broad, slow negativity onsetting around 400-500 ms was largest for sentences with moderately strong constraint. Within this range of constraint, the negativity was larger for sentences with fewer alternative completions compared to those with many different ones. The timing and scalp distribution of the effect resemble brain responses linked to engagement of working memory resources, ambiguity resolution, and comprehension of jokes. Similar to cases of "frame-shifting" in non-literal language, this effect may reflect processing associated with reinterpretation or reconsideration of contextual material when multiple interpretations of a sentence were likely. PMID:22565202

  3. A Bayesian Approach to Estimating Coupling Between Neural Components: Evaluation of the Multiple Component, Event-Related Potential (mcERP) Algorithm

    NASA Astrophysics Data System (ADS)

    Shah, Ankoor S.; Knuth, Kevin H.; Truccolo, Wilson A.; Ding, Mingzhou; Bressler, Steven L.; Schroeder, Charles E.

    2003-03-01

    Accurate measurement of single-trial responses is key to a definitive use of complex electromagnetic and hemodynamic measurements in the investigation of brain dynamics. We developed the multiple component, Event-Related Potential (mcERP) approach to single-trial response estimation to improve our resolution of dynamic interactions between neuronal ensembles located in different layers within a cortical region and/or in different cortical regions. The mcERP model asserts that multiple components defined as stereotypic waveforms comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Maximum a posteriori (MAP) solutions for the model are obtained by iterating a set of equations derived from the posterior probability. Our first goal was to use the mcERP algorithm to analyze interactions (specifically latency and amplitude correlation) between responses in different layers within a cortical region. Thus, we evaluated the model by applying the algorithm to synthetic data containing two correlated local components and one independent far-field component. Three cases were considered: the local components were correlated by an interaction in their single-trial amplitudes, by an interaction in their single-trial latencies, or by an interaction in both amplitude and latency. We then analyzed the accuracy with which the algorithm estimated the component waveshapes and the single-trial parameters as a function of these relationships. Extensions of these analyses to real data are discussed as well as ongoing work to incorporate more detailed prior information.

  4. Rational Design of a Structural Framework with Potential Use to Develop Chemical Reagents That Target and Modulate Multiple Facets of Alzheimer’s Disease

    PubMed Central

    Lee, Sanghyun; Zheng, Xueyun; Krishnamoorthy, Janarthanan; Savelieff, Masha G.; Park, Hyun Min; Brender, Jeffrey R.; Kim, Jin Hoon; Derrick, Jeffrey S.; Kochi, Akiko; Lee, Hyuck Jin; Kim, Cheal; Ramamoorthy, Ayyalusamy; Bowers, Michael T.; Lim, Mi Hee

    2014-01-01

    Alzheimer’s disease (AD) is characterized by multiple, intertwined pathological features, including amyloid-? (A?) aggregation, metal ion dyshomeostasis, and oxidative stress. We report a novel compound (ML) prototype of a rationally designed molecule obtained by integrating structural elements for A? aggregation control, metal chelation, reactive oxygen species (ROS) regulation, and antioxidant activity within a single molecule. Chemical, biochemical, ion mobility mass spectrometric, and NMR studies indicate that the compound ML targets metal-free and metal-bound A? (metal–A?) species, suppresses A? aggregation in vitro, and diminishes toxicity induced by A? and metal-treated A? in living cells. Comparison of ML to its structural moieties (i.e., 4-(dimethylamino)phenol (DAP) and (8-aminoquinolin-2-yl)methanol (1)) for reactivity with A? and metal–A? suggests the synergy of incorporating structural components for both metal chelation and A? interaction. Moreover, ML is water-soluble and potentially brain permeable, as well as regulates the formation and presence of free radicals. Overall, we demonstrate that a rational structure-based design strategy can generate a small molecule that can target and modulate multiple factors, providing a new tool to uncover and address AD complexity. PMID:24397771

  5. UP12, a novel ursolic acid derivative with potential for targeting multiple signaling pathways in hepatocellular carcinoma.

    PubMed

    Dong, Haiyan; Yang, Xiang; Xie, Jingjing; Xiang, Liping; Li, Yuanfang; Ou, Minrui; Chi, Ting; Liu, Zhenhua; Yu, Suhong; Gao, Yu; Chen, Jianzhong; Shao, Jingwei; Jia, Lee

    2015-01-15

    Targeting cancer cell glucose metabolism is a promising strategy for cancer therapy. In past approaches to cancer drug discovery, ursolic acid (UA) has been chemically modified to improve its antitumor activities and bioavailability. Here, a novel ursolic acid (UA) derivative UP12 was developed via computer-aided drug design to explore potent anti-cancer agents and to examine possible mechanisms. The structural docking analyses suggested that UP12 could bind to the active sites of glucokinase (GK), glucose transporter 1 (GLUT1) and ATPase, which are the main enzymes involved in cancer glucose metabolism. We further investigated the synergistic effect between UP12 and glycolysis inhibitor 2-deoxy-d-glucose (2-DG) in inhibiting glucose metabolism of cancer cells. The pharmacological results showed that the combination enhanced depletion of intracellular ATP and decrease in lactate production, and pushed more cancer cells arrested in the S and G2/M cycle phases. The combination selectively down-regulated the expression of Bcl-2 and HKII proteins, up-regulated the expression of Bax and p53, and collectively resulted in enhanced apoptosis related to caspase-3, -8, and -9 activities, in addition to inhibition on the cell mitochondrial membrane potential. The animal studies further demonstrated that the combination exhibited significant antitumor activity without obvious toxicity. In summary, UP12 can interfere cancer cell metabolism pathway and further enhance the therapeutic effects of 2-DG likely through synergistic suppression of cancer cell glucose metabolism, making UP12 a likely new candidate for anti-cancer drug development. PMID:25522955

  6. Multiple Breast Cancer Cell-Lines Derived from a Single Tumor Differ in Their Molecular Characteristics and Tumorigenic Potential

    PubMed Central

    Mosoyan, Goar; Nagi, Chandandeep; Marukian, Svetlana; Teixeira, Avelino; Simonian, Anait; Resnick-Silverman, Lois; DiFeo, Analisa; Johnston, Dean; Reynolds, Sandra R.; Roses, Daniel F.; Mosoian, Arevik

    2013-01-01

    Background Breast cancer cell lines are widely used tools to investigate breast cancer biology and to develop new therapies. Breast cancer tissue contains molecularly heterogeneous cell populations. Thus, it is important to understand which cell lines best represent the primary tumor and have similarly diverse phenotype. Here, we describe the development of five breast cancer cell lines from a single patient’s breast cancer tissue. We characterize the molecular profiles, tumorigenicity and metastatic ability in vivo of all five cell lines and compare their responsiveness to 4-hydroxytamoxifen (4-OHT) treatment. Methods Five breast cancer cell lines were derived from a single patient’s primary breast cancer tissue. Expression of different antigens including HER2, estrogen receptor (ER), CK8/18, CD44 and CD24 was determined by flow cytometry, western blotting and immunohistochemistry (IHC). In addition, a Fuorescent In Situ Hybridization (FISH) assay for HER2 gene amplification and p53 genotyping was performed on all cell lines. A xenograft model in nude mice was utilized to assess the tumorigenic and metastatic abilities of the breast cancer cells. Results We have isolated, cloned and established five new breast cancer cell lines with different tumorigenicity and metastatic abilities from a single primary breast cancer. Although all the cell lines expressed low levels of ER, their growth was estrogen-independent and all had high-levels of expression of mutated non-functional p53. The HER2 gene was rearranged in all cell lines. Low doses of 4-OHT induced proliferation of these breast cancer cell lines. Conclusions All five breast cancer cell lines have different antigenic expression profiles, tumorigenicity and organ specific metastatic abilities although they derive from a single tumor. None of the studied markers correlated with tumorigenic potential. These new cell lines could serve as a model for detailed genomic and proteomic analyses to identify mechanisms of organ-specific metastasis of breast cancer. PMID:23372829

  7. Differentially-expressed genes in rice infected by Xanthomonas oryzae pv. oryzae relative to a flagellin-deficient mutant reveal potential functions of flagellin in host–pathogen interactions

    PubMed Central

    2014-01-01

    Background Plants have evolved a sensitive defense response system that detects and recognizes various pathogen-associated molecular patterns (PAMPs) (e.g. flagellin) and induces immune responses to protect against invasion. Transcriptional responses in rice to PAMPs produced by Xanthomonas oryzae pv. oryzae (Xoo), the bacterial blight pathogen, have not yet been defined. Results We characterized transcriptomic responses in rice inoculated with the wildtype (WT) Xoo and flagellin-deficient mutant ?fliC through RNA-seq analysis. Digital gene expression (DGE) analysis based on Solexa/Illumina sequencing was used to investigate transcriptomic responses in 30 day-old seedlings of rice (Oryza sativa L. cv. Nipponbare). 1,680 genes were differentially-expressed (DEGs) in rice inoculated with WT relative to ?fliC; among which 1,159 genes were up-regulated and 521 were down-regulated. Expression patterns of 12 randomly-selected DEGs assayed by quantitative real time PCR (qRT-PCR) were similar to those detected by DGE analyses, confirming reliability of the DGE data. Functional annotations revealed the up-regulated DEGs are involved in the cell wall, lipid and secondary metabolism, defense response and hormone signaling, whereas the down-regulated ones are associated with photosynthesis. Moreover, 57 and 21 specifically expressed genes were found after WT and ?fliC treatments, respectively. Conclusions DEGs were identified in rice inoculated with WT Xoo relative to ?fliC. These genes were predicted to function in multiple biological processes, including the defense response and photosynthesis in rice. This study provided additional insights into molecular basis of rice response to bacterial infection and revealed potential functions of bacterial flagellin in the rice-Xoo interactions. PMID:25187853

  8. Multiple signatures of a disease in potential biomarker space: Getting the signatures consensus and identification of novel biomarkers

    PubMed Central

    2015-01-01

    Background The lack of consensus among reported gene signature subsets (GSSs) in multi-gene biomarker discovery studies is often a concern for researchers and clinicians. Subsequently, it discourages larger scale prospective studies, prevents the translation of such knowledge into a practical clinical setting and ultimately hinders the progress of the field of biomarker-based disease classification, prognosis and prediction. Methods We define all "gene identificators" (gIDs) as constituents of the entire potential disease biomarker space. For each gID in a GSS of interest ("tested GSS"/tGSS), our method counts the empirical frequency of gID co-occurrences/overlaps in other reference GSSs (rGSSs) and compares it with the expected frequency generated via implementation of a randomized sampling procedure. Comparison of the empirical frequency distribution (EFD) with the expected background frequency distribution (BFD) allows dichotomization of statistically novel (SN) and common (SC) gIDs within the tGSS. Results We identify SN or SC biomarkers for tGSSs obtained from previous studies of high-grade serous ovarian cancer (HG-SOC) and breast cancer (BC). For each tGSS, the EFD of gID co-occurrences/overlaps with other rGSSs is characterized by scale and context-dependent Pareto-like frequency distribution function. Our results indicate that while independently there is little overlap between our tGSS with individual rGSSs, comparison of the EFD with BFD suggests that beyond a confidence threshold, tested gIDs become more common in rGSSs than expected. This validates the use of our tGSS as individual or combined prognostic factors. Our method identifies SN and SC genes of a 36-gene prognostic signature that stratify HG-SOC patients into subgroups with low, intermediate or high-risk of the disease outcome. Using 70 BC rGSSs, the method also predicted SN and SC BC prognostic genes from the tested obesity and IGF1 pathway GSSs. Conclusions Our method provides a strategy that identify/predict within a tGSS of interest, gID subsets that are either SN or SC when compared to other rGSSs. Practically, our results suggest that there is a stronger association of the IGF1 signature genes with the 70 BC rGSSs, than for the obesity-associated signature. Furthermore, both SC and SN genes, in both signatures could be considered as perspective prognostic biomarkers of BCs that stratify the patients onto low or high risks of cancer development. PMID:26100469

  9. Differential Atmospheric Controls on Transpiration of Boreal Trees: A Potential Factor in Pre-mature Tree Mortality in Green-Tree Retention Strategies

    NASA Astrophysics Data System (ADS)

    Bladon, K. D.; Silins, U.; Lieffers, V. J.

    2004-05-01

    Green-tree retention, a harvesting strategy that involves the preservation of isolated and interconnected patches of live trees within the boundaries of harvested areas, is assumed to emulate natural disturbance, while preserving forest canopy continuity for wildlife habitat, maintaining forest biodiversity, and many other landscape level objectives. Unfortunately, many of the retention trees die within a few years after harvesting, thus much of the desired function of these trees is lost. This research focuses on understanding the relationship between changes in micro-climate following harvesting and transpiration, potentially leading to drought-induced mortality of aspen, balsam poplar, white spruce, and white birch. Continuous measurements of whole-tree water use (sap flow) and micro-climate were taken before and after harvesting of two adjacent boreal mixedwood stands in west-central Alberta in the summer of 2003. Differences in micro-climate including radiation, air temperature, relative humidity and wind penetration into the canopy produced large differences in atmospheric moisture demand (PET) between partially harvested (green-tree retention) and undisturbed forest canopies. The variability in atmospheric conditions created large differences in sap flow velocity and transpiration rates among these four boreal species. Differential transpiration rates among species will be discussed in context of atmospheric controls on water use and drought tolerance of boreal trees with differing autecology and/or hydraulic architecture.

  10. Rapid differentiation and identification of potential severe strains of Citrus tristeza virus by real-time reverse transcription-polymerase chain reaction assays.

    PubMed

    Yokomi, R K; Saponari, M; Sieburth, P J

    2010-04-01

    A multiplex Taqman-based real-time reverse transcription (RT) polymerase chain reaction (PCR) assay was developed to identify potential severe strains of Citrus tristeza virus (CTV) and separate genotypes that react with the monoclonal antibody MCA13. Three strain-specific probes were developed using intergene sequences between the major and minor coat protein genes (CPi) in a multiplex reaction. Probe CPi-VT3 was designed for VT and T3 genotypes; probe CPi-T36 for T36 genotypes; and probe CPi-T36-NS to identify isolates in an outgroup clade of T36-like genotypes mild in California. Total nucleic acids extracted by chromatography on silica particles, sodium dodecyl sulfate-potassium acetate, and CTV virion immunocapture all yielded high quality templates for real-time PCR detection of CTV. These assays successfully differentiated CTV isolates from California, Florida, and a large panel of CTV isolates from an international collection maintained in Beltsville, MD. The utility of the assay was validated using field isolates collected in California and Florida. PMID:20205535

  11. Multiple-Symbol Detection Of Multiple-Trellis-Coded MDPSK

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

    In proposed scheme for detection and decoding of multiple-trellis-coded multilevel differential-phase-shift-keyed (MDPSK) radio signals, observation time for differential detection extended from conventional 2 to larger number of symbol periods. Decreases rate of error in differential detection of uncoded MDPSK by increasing number of symbol periods.

  12. Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target

    PubMed Central

    Tomecki, Rafal; Drazkowska, Karolina; Kucinski, Iwo; Stodus, Krystian; Szczesny, Roman J.; Gruchota, Jakub; Owczarek, Ewelina P.; Kalisiak, Katarzyna; Dziembowski, Andrzej

    2014-01-01

    hDIS3 is a mainly nuclear, catalytic subunit of the human exosome complex, containing exonucleolytic (RNB) and endonucleolytic (PIN) active domains. Mutations in hDIS3 have been found in ?10% of patients with multiple myeloma (MM). Here, we show that these mutations interfere with hDIS3 exonucleolytic activity. Yeast harboring corresponding mutations in DIS3 show growth inhibition and changes in nuclear RNA metabolism typical for exosome dysfunction. Construction of a conditional DIS3 knockout in the chicken DT40 cell line revealed that DIS3 is essential for cell survival, indicating that its function cannot be replaced by other exosome-associated nucleases: hDIS3L and hRRP6. Moreover, HEK293-derived cells, in which depletion of endogenous wild-type hDIS3 was complemented with exogenously expressed MM hDIS3 mutants, proliferate at a slower rate and exhibit aberrant RNA metabolism. Importantly, MM mutations are synthetically lethal with the hDIS3 PIN domain catalytic mutation both in yeast and human cells. Since mutations in PIN domain alone have little effect on cell physiology, our results predict the hDIS3 PIN domain as a potential drug target for MM patients with hDIS3 mutations. It is an interesting example of intramolecular synthetic lethality with putative therapeutic potential in humans. PMID:24150935

  13. Multiple myeloma-associated hDIS3 mutations cause perturbations in cellular RNA metabolism and suggest hDIS3 PIN domain as a potential drug target.

    PubMed

    Tomecki, Rafal; Drazkowska, Karolina; Kucinski, Iwo; Stodus, Krystian; Szczesny, Roman J; Gruchota, Jakub; Owczarek, Ewelina P; Kalisiak, Katarzyna; Dziembowski, Andrzej

    2014-01-01

    hDIS3 is a mainly nuclear, catalytic subunit of the human exosome complex, containing exonucleolytic (RNB) and endonucleolytic (PIN) active domains. Mutations in hDIS3 have been found in ?10% of patients with multiple myeloma (MM). Here, we show that these mutations interfere with hDIS3 exonucleolytic activity. Yeast harboring corresponding mutations in DIS3 show growth inhibition and changes in nuclear RNA metabolism typical for exosome dysfunction. Construction of a conditional DIS3 knockout in the chicken DT40 cell line revealed that DIS3 is essential for cell survival, indicating that its function cannot be replaced by other exosome-associated nucleases: hDIS3L and hRRP6. Moreover, HEK293-derived cells, in which depletion of endogenous wild-type hDIS3 was complemented with exogenously expressed MM hDIS3 mutants, proliferate at a slower rate and exhibit aberrant RNA metabolism. Importantly, MM mutations are synthetically lethal with the hDIS3 PIN domain catalytic mutation both in yeast and human cells. Since mutations in PIN domain alone have little effect on cell physiology, our results predict the hDIS3 PIN domain as a potential drug target for MM patients with hDIS3 mutations. It is an interesting example of intramolecular synthetic lethality with putative therapeutic potential in humans. PMID:24150935

  14. Multiple Legionella pneumophila Type II Secretion Substrates, Including a Novel Protein, Contribute to Differential Infection of the Amoebae Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria lovaniensis

    PubMed Central

    Tyson, Jessica Y.; Pearce, Meghan M.; Vargas, Paloma; Bagchi, Sreya; Mulhern, Brendan J.

    2013-01-01

    Type II protein secretion (T2S) by Legionella pneumophila is required for intracellular infection of host cells, including macrophages and the amoebae Acanthamoeba castellanii and Hartmannella vermiformis. Previous proteomic analysis revealed that T2S by L. pneumophila 130b mediates the export of >25 proteins, including several that appeared to be novel. Following confirmation that they are unlike known proteins, T2S substrates NttA, NttB, and LegP were targeted for mutation. nttA mutants were impaired for intracellular multiplication in A. castellanii but not H. vermiformis or macrophages, suggesting that novel exoproteins which are specific to Legionella are especially important for infection. Because the importance of NttA was host cell dependent, we examined a panel of T2S substrate mutants that had not been tested before in more than one amoeba. As a result, RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all proved to be required for optimal intracellular multiplication in H. vermiformis but not A. castellanii. Further examination of an lspF mutant lacking the T2S apparatus documented that T2S is also critical for infection of the amoeba Naegleria lovaniensis. Mutants lacking SrnA, PlaC, or ProA, but not those deficient for NttA, were defective in N. lovaniensis. Based upon analysis of a double mutant lacking PlaC and ProA, the role of ProA in H. vermiformis was connected to its ability to activate PlaC, whereas in N. lovaniensis, ProA appeared to have multiple functions. Together, these data document that the T2S system exports multiple effectors, including a novel one, which contribute in different ways to the broad host range of L. pneumophila. PMID:23429532

  15. Multiple regulation by calcium of murine homologues of transient receptor potential proteins TRPC6 and TRPC7 expressed in HEK293 cells

    PubMed Central

    Shi, Juan; Mori, Emiko; Mori, Yasuo; Mori, Masayuki; Li, Jishuo; Ito, Yushi; Inoue, Ryuji

    2004-01-01

    We investigated, by using the patch clamp technique, Ca2+-mediated regulation of heterologously expressed TRPC6 and TRPC7 proteins in HEK293 cells, two closely related homologues of the transient receptor potential (TRP) family and molecular candidates for native receptor-operated Ca2+ entry channels. With nystatin-perforated recording, the magnitude and time courses of activation and inactivation of carbachol (CCh; 100 ?m)-activated TRPC6 currents (ITRPC6) were enhanced and accelerated, respectively, by extracellular Ca2+ (Ca2o+) whether it was continuously present or applied after receptor stimulation. In contrast, Ca2o+ solely inhibited TRPC7 currents (ITRPC7). Vigorous buffering of intracellular Ca2+ (Ca2i+) under conventional whole-cell clamp abolished the slow potentiating (i.e. accelerated activation) and inactivating effects of Ca2o+, disclosing fast potentiation (EC50: ?0.4 mm) and inhibition (IC50: ?4 mm) of ITRPC6 and fast inhibition (IC50: ?0.4 mm) of ITRPC7. This inhibition of ITRPC6 and ITRPC7 seems to be associated with voltage-dependent reductions of unitary conductance and open probability at the single channel level, whereas the potentiation of ITRPC6 showed little voltage dependence and was mimicked by Sr2+ but not Ba2+. The activation process of ITRPC6 or its acceleration by Ca2o+ probably involves phosphorylation by calmodulin (CaM)-dependent kinase II (CaMKII), as pretreatment with calmidazolium (3 ?m), coexpression of Ca2+-insesentive mutant CaM, and intracellular perfusion of the non-hydrolysable ATP analogue AMP-PNP and a CaMKII-specific inhibitory peptide all effectively prevented channel activation. However, this was not observed for TRPC7. Instead, single CCh-activated TRPC7 channel activity was concentration-dependently suppressed by nanomolar Ca2i+ via CaM and conversely enhanced by IP3. In addition, the inactivation time course of ITRPC6 was significantly retarded by pharmacological inhibition of protein kinase C (PKC). These results collectively suggest that TRPC6 and 7 channels are multiply regulated by Ca2+ from both sides of the membrane through differential Ca2+?CaM-dependent and -independent mechanisms. PMID:15579537

  16. MUPEMURE Multiple Perspectives on Multiple

    E-print Network

    Paris-Sud XI, Université de

    MUPEMURE ­ Multiple Perspectives on Multiple Representations White Paper Organizers: The MUPEMURE-00722956,version1-6Aug2012 #12; MUPEMURE ­ Multiple Perspectives on Multiple Representations Seite 1 MUPEMURE ­ Multiple Perspectives on Multiple Representations White Paper 1. Introduction and Motivation Our

  17. p53Independent Expression of p21Cip1 in Muscle and Other Terminally Differentiating Cells

    Microsoft Academic Search

    Susan B. Parker; Gregor Eichele; Pumin Zhang; Alan Rawls; Arthur T. Sands; Allan Bradley; Eric N. Olson; J. Wade Harper; Stephen J. Elledge

    1995-01-01

    Terminal differentiation is coupled to withdrawal from the cell cycle. The cyclin-dependent kinase inhibitor (CKI) p21Cip1 is transcriptionally regulated by p53 and can induce growth arrest. CKIs are therefore potential mediators of developmental control of cell proliferation. The expression pattern of mouse p21 correlated with terminal differentiation of multiple cell lineages including skeletal muscle, cartilage, skin, and nasal epithelium in

  18. A Bayesian Approach to Estimating Coupling Between Neural Components: Evaluation of the Multiple Component, Event-Related Potential (mcERP) Algorithm

    NASA Technical Reports Server (NTRS)

    Shah, Ankoor S.; Knuth, Kevin H.; Truccolo, Wilson A.; Ding, Ming-Zhou; Bressler, Steven L.; Schroeder, Charles E.; Clancy, Daniel (Technical Monitor)

    2002-01-01

    Accurate measurement of single-trial responses is key to a definitive use of complex electromagnetic and hemodynamic measurements in the investigation of brain dynamics. We developed the multiple component, Event-Related Potential (mcERP) approach to single-trial response estimation. To improve our resolution of dynamic interactions between neuronal ensembles located in different layers within a cortical region and/or in different cortical regions. The mcERP model assets that multiple components defined as stereotypic waveforms comprise the stimulus-evoked response and that these components may vary in amplitude and latency from trial to trial. Maximum a posteriori (MAP) solutions for the model are obtained by iterating a set of equations derived from the posterior probability. Our first goal was to use the ANTWERP algorithm to analyze interactions (specifically latency and amplitude correlation) between responses in different layers within a cortical region. Thus, we evaluated the model by applying the algorithm to synthetic data containing two correlated local components and one independent far-field component. Three cases were considered: the local components were correlated by an interaction in their single-trial amplitudes, by an interaction in their single-trial latencies, or by an interaction in both amplitude and latency. We then analyzed the accuracy with which the algorithm estimated the component waveshapes and the single-trial parameters as a function of the linearity of each of these relationships. Extensions of these analyses to real data are discussed as well as ongoing work to incorporate more detailed prior information.

  19. Extensive sampling of polar bears (Ursus maritimus) in the Northwest Passage (Canadian Arctic Archipelago) reveals population differentiation across multiple spatial and temporal scales

    PubMed Central

    Campagna, Leonardo; Van Coeverden de Groot, Peter J; Saunders, Brenda L; Atkinson, Stephen N; Weber, Diana S; Dyck, Markus G; Boag, Peter T; Lougheed, Stephen C

    2013-01-01

    As global warming accelerates the melting of Arctic sea ice, polar bears (Ursus maritimus) must adapt to a rapidly changing landscape. This process will necessarily alter the species distribution together with population dynamics and structure. Detailed knowledge of these changes is crucial to delineating conservation priorities. Here, we sampled 361 polar bears from across the center of the Canadian Arctic Archipelago spanning the Gulf of Boothia (GB) and M'Clintock Channel (MC). We use DNA microsatellites and mitochondrial control region sequences to quantify genetic differentiation, estimate gene flow, and infer population history. Two populations, roughly coincident with GB and MC, are significantly differentiated at both nuclear (FST = 0.01) and mitochondrial (?ST = 0.47; FST = 0.29) loci, allowing Bayesian clustering analyses to assign individuals to either group. Our data imply that the causes of the mitochondrial and nuclear genetic patterns differ. Analysis of mtDNA reveals the matrilineal structure dates at least to the Holocene, and is common to individuals throughout the species’ range. These mtDNA differences probably reflect both genetic drift and historical colonization dynamics. In contrast, the differentiation inferred from microsatellites is only on the scale of hundreds of years, possibly reflecting contemporary impediments to gene flow. Taken together, our data suggest that gene flow is insufficient to homogenize the GB and MC populations and support the designation of GB and MC as separate polar bear conservation units. Our study also provide a striking example of how nuclear DNA and mtDNA capture different aspects of a species demographic history. PMID:24102001

  20. Antibody responses to inactivated vaccines and natural infection in cattle using bovine viral diarrhoea virus ELISA kits: Assessment of potential to differentiate infected and vaccinated animals

    Microsoft Academic Search

    Rüdiger Raue; Silke S. Harmeyer; Ian A. Nanjiani

    2011-01-01

    Bovine viral diarrhoea virus (BVDV) is one of the most common and economically important viral infections of cattle. As vaccination is common in most European countries, differentiation between infected and vaccinated animals is one of the key challenges facing BVDV eradication campaigns. This study was designed to compare the ability of commercial ELISA kits to differentiate antibodies generated following vaccination

  1. Chronic thromboembolic pulmonary hypertension (CTEPH) - potential role of multidetector-row CT (MD-CT) and MR imaging in the diagnosis and differential diagnosis of the disease.

    PubMed

    Wirth, G; Brüggemann, K; Bostel, T; Mayer, E; Düber, C; Kreitner, K F

    2014-08-01

    Chronic thromboembolic pulmonary hypertension (CTEPH) can be defined as pulmonary hypertension (resting mean pulmonary arterial pressure of 25 mm Hg or more determined at right heart catheterization) with persistent pulmonary perfusion defects. It is a rare, but underdiagnosed disease with estimated incidences ranging from 0.5% to 3.8% of patients after an acute pulmonary embolism (PE), and in up to 10% of those with a history of recurrent PE. CTEPH is the only form of pulmonary hypertension that can be surgically treated leading to normalization of pulmonary hemodynamics and exercise capacity in the vast majority of patients. The challenges for imaging in patients with suspected CTEPH are fourfold: the imaging modality should have a high diagnostic accuracy with regard to the presence of CTEPH and allow for differential diagnosis. It should enable detection of patients suitable for PEA with great certainty, and allow for quantification of PH by measuring pulmonary hemodynamics (mPAP and PVR), and finally, it can be used for therapy monitoring. This overview tries to elucidate the potential role of ECG-gated multidetector CT pulmonary angiography (MD-CTPA) and MR imaging, and summarizes the most important results that have been achieved so far. Generally speaking, ECG-gated MD-CTPA is superior to MR in the assessment of parenchymal and vascular pathologies of the lung, and allows for the assessment of cardiac structures. The implementation of iodine maps as a surrogate for lung perfusion enables functional assessment of lung perfusion by CT. MR imaging is the reference standard for the assessment of right heart function and lung perfusion, the latter delineating typical wedge-shaped perfusion defects in patients with CTEPH. New developments show that with MR techniques, an estimation of hemodynamic parameters like mean pulmonary arterial pressure and pulmonary vascular resistance will be possible. CT and MR imaging should be considered as complementary investigations providing comprehensive information in patients with CTEPH. PMID:24756429

  2. Identification and Validation of Differential Phosphorylation Sites of the Nuclear FOXL2 Protein as Potential Novel Biomarkers for Adult-Type Granulosa Cell Tumors.

    PubMed

    Suh, Dae-Shik; Oh, Hoon Kyu; Kim, Jae-Hong; Park, Seeun; Shin, Eunkyoung; Lee, Kangseok; Kim, Yong-Hak; Bae, Jeehyeon

    2015-06-01

    Granulosa cell tumor (GCT) is a rare form of ovarian cancer classified as a sex cord-stromal tumor. The c.402C?G missense mutation in the FOXL2 gene that changes cysteine 134 to tryptophan (C134W) is found in more than 97% of adult-type GCTs, and the C134W FOXL2 mutant is hyperphosphorylated. We identified three differential phosphorylation sites, at serine 33 (S33), tyrosine 186 (Y186), and serine 238 (S238), of the C134W mutant by tandem mass spectrometry. Among these sites, antibodies were raised against the pS33 and pY186 epitopes using specific peptides, and they were tested by immunostaining tissue microarrays of archival adult-type GCT specimens, other tumors, and normal tissues. The pS33 antibody showed greater sensitivity and specificity for the detection of adult-type GCTs than that of the other phospho and nonphospho antibodies. The specificity of the pS33 antibody to the pS33 epitope was further confirmed by enriching the pS33 peptide by affinity chromatography using the immobilized antibody, followed by mass spectrometric and western blot analyses from whole cell lysates of the adult-type GCT cell line, KGN. pS33 FOXL2 immunostaining levels were significantly higher in adult-type GCTs than those in other tumors and tissues. The receiver operating characteristic curve analysis of pS33 FOXL2 showed high sensitivity (1.0) and specificity (0.76) to adult-type GCTs with a cutoff score of >30% positive cells, and the area under the curve was 0.96. This suggests the potential of pS33 FOXL2 to serve as a new biomarker for the diagnosis of adult-type GCT. PMID:25871347

  3. Early in-flight detection of SO2 via Differential Optical Absorption Spectroscopy: A feasible aviation safety measure to prevent potential encounters with volcanic plumes

    USGS Publications Warehouse

    Vogel, L.; Galle, B.; Kern, C.; Delgado, Granados H.; Conde, V.; Norman, P.; Arellano, S.; Landgren, O.; Lubcke, P.; Alvarez, Nieves J.M.; Cardenas, Gonzales L.; Platt, U.

    2011-01-01

    Volcanic ash constitutes a risk to aviation, mainly due to its ability tocause jet engines to fail. Other risks include the possibility of abrasion ofwindshields and potentially serious damage to avionic systems. These hazardshave been widely recognized since the early 1980s, when volcanic ash provokedseveral incidents of engine failure in commercial aircraft. In addition tovolcanic ash, volcanic gases also pose a threat. Prolonged and/or cumulativeexposure to sulphur dioxide (SO2) or sulphuric acid (H2SO4)aerosols potentially affects e.g. windows, air frame and may cause permanentdamage to engines. SO2 receives most attention among the gas speciescommonly found in volcanic plumes because its presence above the lowertroposphere is a clear proxy for a volcanic cloud and indicates that fine ashcould also be present. Up to now, remote sensing of SO2 via Differential Optical AbsorptionSpectroscopy (DOAS) in the ultraviolet spectral region has been used tomeasure volcanic clouds from ground based, airborne and satellite platforms.Attention has been given to volcanic emission strength, chemistry insidevolcanic clouds and measurement procedures were adapted accordingly. Here wepresent a set of experimental and model results, highlighting the feasibilityof DOAS to be used as an airborne early detection system of SO2 intwo spatial dimensions. In order to prove our new concept, simultaneousairborne and ground-based measurements of the plume of Popocat??petlvolcano, Mexico, were conducted in April 2010. The plume extended at analtitude around 5250 m above sea level and was approached and traversed at thesame altitude with several forward looking DOAS systems aboard an airplane.These DOAS systems measured SO2 in the flight direction and at?? 40 mrad (2.3??) angles relative to it in both, horizontal andvertical directions. The approaches started at up to 25 km distance to theplume and SO2 was measured at all times well above the detectionlimit. In combination with radiative transfer studies, this study indicatesthat an extended volcanic cloud with a concentration of 1012 molecules cm-3 at typical flight levels of 10 km can be detectedunambiguously at distances of up to 80 km away. This range provides enoughtime (approx. 5 min) for pilots to take action to avoid entering avolcanic cloud in the flight path, suggesting that this technique can be usedas an effective aid to prevent dangerous aircraft encounters with potentiallyash rich volcanic clouds. ?? Author(s) 2011.

  4. Assessing the potential impact of non-proprietary drug copies on quality of medicine and treatment in patients with relapsing multiple sclerosis: the experience with fingolimod

    PubMed Central

    Correale, Jorge; Chiquete, Erwin; Milojevic, Snezana; Frider, Nadina; Bajusz, Imre

    2014-01-01

    Background Fingolimod is a once-daily oral treatment for relapsing multiple sclerosis, the proprietary production processes of which are tightly controlled, owing to its susceptibility to contamination by impurities, including genotoxic impurities. Many markets produce nonproprietary medicines; assessing their efficacy and safety is difficult as regulators may approve nonproprietary drugs without bioequivalence data, genotoxic evaluation, or risk management plans (RMPs). This assessment is especially important for fingolimod given its solubility/bioavailability profile, genotoxicity risk, and low-dose final product (0.5 mg). This paper presents an evaluation of the quality of proprietary and nonproprietary fingolimod variants. Methods Proprietary fingolimod was used as a reference substance against which eleven nonproprietary fingolimod copies were assessed. The microparticle size distribution of each compound was assessed by laser light diffraction, and inorganic impurity content by sulfated ash testing. Heavy metals content was quantified using inductively coupled plasma optical emission spectrometry, and levels of unspecified impurities by high-performance liquid chromatography. Solubility was assessed in a range of solvents at different pH values. Key information from the fingolimod RMP is also presented. Results Nonproprietary fingolimod variants exhibited properties out of proprietary or internationally accepted specifications, including differences in particle size distribution and levels of impurities such as heavy metals. For microparticle size and heavy metals, all tested fingolimod copies were out-of-specification by several-fold magnitudes. Proprietary fingolimod has a well-defined RMP, highlighting known and potential mid- to long-term safety risks, and risk-minimization and pharmacovigilance procedures. Conclusion Nonproprietary fingolimod copies produced by processes less well controlled than or altered from proprietary production processes may reduce product reproducibility and quality, potentially presenting risks to patients. Safety data and risk-minimization strategies for proprietary fingolimod may not apply to the nonproprietary fingolimod copies evaluated here. Market authorization of nonproprietary fingolimod copies should require an appropriate RMP to minimize risks to patients. PMID:25028537

  5. Differentiation of closely related isomers: application of data mining techniques in conjunction with variable wavelength infrared multiple photon dissociation mass spectrometry for identification of glucose-containing disaccharide ions.

    PubMed

    Stefan, Sarah E; Ehsan, Mohammad; Pearson, Wright L; Aksenov, Alexander; Boginski, Vladimir; Bendiak, Brad; Eyler, John R

    2011-11-15

    Data mining algorithms have been used to analyze the infrared multiple photon dissociation (IRMPD) patterns of gas-phase lithiated disaccharide isomers irradiated with either a line-tunable CO(2) laser or a free electron laser (FEL). The IR fragmentation patterns over the wavelength range of 9.2-10.6 ?m have been shown in earlier work to correlate uniquely with the asymmetry at the anomeric carbon in each disaccharide. Application of data mining approaches for data analysis allowed unambiguous determination of the anomeric carbon configurations for each disaccharide isomer pair using fragmentation data at a single wavelength. In addition, the linkage positions were easily assigned. This combination of wavelength-selective IRMPD and data mining offers a powerful and convenient tool for differentiation of structurally closely related isomers, including those of gas-phase carbohydrate complexes. PMID:21954928

  6. Erythropoietin-Stimulating Agents and Survival in End-Stage Renal Disease: Comparison of Payment Policy Analysis, Instrumental Variables, and Multiple Imputation of Potential Outcomes

    PubMed Central

    Dore, David D.; Swaminathan, Shailender; Gutman, Roee; Trivedi, Amal N.; Mor, Vincent

    2013-01-01

    Objective To compare the assumptions and estimands across three approaches to estimating the effect of erythropoietin-stimulating agents (ESAs) on mortality. Study Design and Setting Using data from the Renal Management Information System, we conducted two analyses utilizing a change to bundled payment that we hypothesized mimicked random assignment to ESA (pre-post, difference-in-difference, and instrumental variable analyses). A third analysis was based on multiply imputing potential outcomes using propensity scores. Results There were 311,087 recipients of ESAs and 13,095 non-recipients. In the pre-post comparison, we identified no clear relationship between bundled payment (measured by calendar time) and the incidence of death within six months (risk difference -1.5%; 95% CI - 7.0% to 4.0%). In the instrumental variable analysis, the risk of mortality was similar among ESA recipients (risk difference -0.9%; 95% CI -2.1 to 0.3). In the multiple imputation analysis, we observed a 4.2% (95% CI 3.4% to 4.9%) absolute reduction in mortality risk with use of ESAs, but closer to the null for patients with baseline hematocrit >36%. Conclusion Methods emanating from different disciplines often rely on different assumptions, but can be informative about a similar causal contrast. The implications of these distinct approaches are discussed. PMID:23849152

  7. Inhibition deficit in the spatial tendency of the response in multiple-domain amnestic mild cognitive impairment. An event-related potential study.

    PubMed

    Cespón, Jesús; Galdo-Álvarez, Santiago; Díaz, Fernando

    2015-01-01

    Longitudinal studies have shown that a high percentage of people with amnestic mild cognitive impairment (MCI) develop Alzheimer's disease (AD). Prodromal AD is known to involve deficits in executive control processes. In the present study, we examined such deficits by recording EEG in 13 single-domain amnestic MCI (sdaMCI), 12 multiple-domain amnestic MCI (mdaMCI) and 18 healthy elderly (control group, CG) participants while they performed a Simon task. The Simon task demands deployment of executive processes because participants have to respond to non-spatial features of a lateralized stimulus and inhibit the more automatic spatial tendency of the response. We specifically focused on the negativity central contralateral (N2cc), an event-related potential (ERP) component related to brain activity that prevents the cross-talk between direction of spatial attention and manual response preparation. The reaction time (RT) was not significantly different among the three groups of participants. The percentage of errors (PE) was higher in mdaMCI than in CG and sdaMCI participants. In addition, N2cc latency was delayed in mdaMCI (i.e., delayed implementation of mechanisms for controlling the spatial tendency of the response). The N2cc latency clearly distinguished among mdaMCI and CG/sdaMCI participants (area under curve: 0.91). Longer N2cc was therefore associated with executive control deficits, which suggests that N2cc latency is a correlate of mdaMCI. PMID:25999853

  8. MicroRNA Expression Profiling of Oligodendrocyte Differentiation from Human Embryonic Stem Cells

    Microsoft Academic Search

    Brian S. Letzen; Cyndi Liu; Nitish V. Thakor; John D. Gearhart; Angelo H. All; Candace L. Kerr; Rafael Linden

    2010-01-01

    BackgroundCells of the oligodendrocyte (OL) lineage play a vital role in the production and maintenance of myelin, a multilamellar membrane which allows for saltatory conduction along axons. These cells may provide immense therapeutic potential for lost sensory and motor function in demyelinating conditions, such as spinal cord injury, multiple sclerosis, and transverse myelitis. However, the molecular mechanisms controlling OL differentiation

  9. Live Cell Monitoring of hiPSC Generation and Differentiation Using Differential Expression of Endogenous microRNAs

    Microsoft Academic Search

    Masakazu Kamata; Min Liang; Shirley Liu; Yoshiko Nagaoka; Irvin S. Y. Chen; David S. Milstone

    2010-01-01

    Human induced pluripotent stem cells (hiPSCs) provide new possibilities for regenerative therapies. In order for this potential to be achieved, it is critical to efficiently monitor the differentiation of these hiPSCs into specific lineages. Here, we describe a lentiviral reporter vector sensitive to specific microRNAs (miRNA) to show that a single vector bearing multiple miRNA target sequences conjugated to different

  10. Molecular phylogeny of RPB2 gene reveals multiple origin, geographic differentiation of H genome, and the relationship of the Y genome to other genomes in Elymus species.

    PubMed

    Sun, Genlou; Ni, Yan; Daley, Tracy

    2008-03-01

    It has been hypothesized from isozymic and cytological studies of Elymus species that the Old and New World taxa may be of separate origin of the H genome in the StH genome species. To test this hypothesis, and estimate the phylogenetic relationships of polyploid Elymus species within the Triticeae, the second largest subunit of RNA polymerase II (RPB2) sequence of 36 Elymus accessions containing StH or StY genomes was analyzed with those of Pseudoroegneria (St), Hordeum (H), Agropyron (P), Australopyrum (W), Lophopyrum(Ee), Thinopyrum(Eb) and Dasypyrum (V). Our data indicated that the H genome in Elymus species is differentiated in accordance with geographical origin, and that the Eurasian and American StH genome species have independent alloploid origins with different H-genome donors. Phylogenetic analysis of Y genome sequences with other genome donors (St, H, P, W) of Elymus revealed that W and P genomes are sister to Y genome with a 87% bootstrap support, and that StY and StH species group might have acquired their RPB2 St sequences from distinct Pseudoroegneria gene pools. Our data did not support the suggestion that the St and Y genomes have the same origin as put forward in a previous study using ITS data. Our result provides some insight on the origin of Y genome and its relationship to other genomes in Elymus. PMID:18262439

  11. The PRKAA1/AMPK?1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML.

    PubMed

    Obba, Sandrine; Hizir, Zoheir; Boyer, Laurent; Selimoglu-Buet, Dorothée; Pfeifer, Anja; Michel, Gregory; Hamouda, Mohamed-Amine; Gonçalvčs, Diogo; Cerezo, Michael; Marchetti, Sandrine; Rocchi, Stephane; Droin, Nathalie; Cluzeau, Thomas; Robert, Guillaume; Luciano, Frederic; Robaye, Bernard; Foretz, Marc; Viollet, Benoit; Legros, Laurence; Solary, Eric; Auberger, Patrick; Jacquel, Arnaud

    2015-07-01

    Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML. PMID:26029847

  12. Effects of multiple daily genistein treatments on delayed alternation and a differential reinforcement of low rates of responding task in middle-aged rats.

    PubMed

    Neese, Steven L; Bandara, Suren B; Doerge, Daniel R; Helferich, William G; Korol, Donna L; Schantz, Susan L