The T-ALL related gene BCL11B regulates the initial stages of human T-cell differentiation.

Science.gov (United States)

Ha, V L; Luong, A; Li, F; Casero, D; Malvar, J; Kim, Y M; Bhatia, R; Crooks, G M; Parekh, C

2017-11-01

The initial stages of T-cell differentiation are characterized by a progressive commitment to the T-cell lineage, a process that involves the loss of alternative (myelo-erythroid, NK, B) lineage potentials. Aberrant differentiation during these stages can result in T-cell acute lymphoblastic leukemia (T-ALL). However, the mechanisms regulating the initial stages of human T-cell differentiation are obscure. Through loss of function studies, we showed BCL11B, a transcription factor recurrently mutated T-ALL, is essential for T-lineage commitment, particularly the repression of NK and myeloid potentials, and the induction of T-lineage genes, during the initial stages of human T-cell differentiation. In gain of function studies, BCL11B inhibited growth of and induced a T-lineage transcriptional program in T-ALL cells. We found previously unknown differentiation stage-specific DNA binding of BCL11B at multiple T-lineage genes; target genes showed BCL11B-dependent expression, suggesting a transcriptional activator role for BCL11B at these genes. Transcriptional analyses revealed differences in the regulatory actions of BCL11B between human and murine thymopoiesis. Our studies show BCL11B is a key regulator of the initial stages of human T-cell differentiation and delineate the BCL11B transcriptional program, enabling the dissection of the underpinnings of normal T-cell differentiation and providing a resource for understanding dysregulations in T-ALL.

Singular Initial Value Problem for Certain Classes of Systems of Ordinary Differential Equations

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Josef Diblík

2013-01-01

dimension of the set of initial data generating such solutions is estimated. An asymptotic behavior of solutions is determined as well and relevant asymptotic formulas are derived. The method of functions defined implicitly and the topological method (Ważewski's method are used in the proofs. The results generalize some previous ones on singular initial value problems for differential equations.

CD36 is required for myoblast fusion during myogenic differentiation

International Nuclear Information System (INIS)

Park, Seung-Yoon; Yun, Youngeun; Kim, In-San

2012-01-01

Highlights: ► CD36 expression was induced during myogenic differentiation. ► CD36 expression was localized in multinucleated myotubes. ► The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. ► Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

CD36 is required for myoblast fusion during myogenic differentiation

Energy Technology Data Exchange (ETDEWEB)

Park, Seung-Yoon [Department of Biochemistry, College of Medicine, Dongguk University and Medical Institute of Dongguk University, Gyeongju 780-714 (Korea, Republic of); Yun, Youngeun [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, In-San, E-mail: iskim@knu.ac.kr [Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Biomedical Research Institute, Korea Institute Science and Technology, Seoul (Korea, Republic of)

2012-11-02

Highlights: Black-Right-Pointing-Pointer CD36 expression was induced during myogenic differentiation. Black-Right-Pointing-Pointer CD36 expression was localized in multinucleated myotubes. Black-Right-Pointing-Pointer The expression of myogenic markers is attenuated in CD36 knockdown C2C12 cells. Black-Right-Pointing-Pointer Knockdown of CD36 significantly inhibited myotube formation during differentiation. -- Abstract: Recently, CD36 has been found to be involved in the cytokine-induced fusion of macrophage. Myoblast fusion to form multinucleated myotubes is required for myogenesis and muscle regeneration. Because a search of gene expression database revealed the attenuation of CD36 expression in the muscles of muscular dystrophy patients, the possibility that CD36 could be required for myoblast fusion was investigated. CD36 expression was markedly up-regulated during myoblast differentiation and localized in multinucleated myotubes. Knockdown of endogenous CD36 significantly decreased the expression of myogenic markers as well as myotube formation. These results support the notion that CD36 plays an important role in cell fusion during myogenic differentiation. Our finding will aid the elucidation of the common mechanism governing cell-to-cell fusion in various fusion models.

Symbolic computation of analytic approximate solutions for nonlinear differential equations with initial conditions

Science.gov (United States)

Lin, Yezhi; Liu, Yinping; Li, Zhibin

2012-01-01

The Adomian decomposition method (ADM) is one of the most effective methods for constructing analytic approximate solutions of nonlinear differential equations. In this paper, based on the new definition of the Adomian polynomials, and the two-step Adomian decomposition method (TSADM) combined with the Padé technique, a new algorithm is proposed to construct accurate analytic approximations of nonlinear differential equations with initial conditions. Furthermore, a MAPLE package is developed, which is user-friendly and efficient. One only needs to input a system, initial conditions and several necessary parameters, then our package will automatically deliver analytic approximate solutions within a few seconds. Several different types of examples are given to illustrate the validity of the package. Our program provides a helpful and easy-to-use tool in science and engineering to deal with initial value problems. Program summaryProgram title: NAPA Catalogue identifier: AEJZ_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEJZ_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 4060 No. of bytes in distributed program, including test data, etc.: 113 498 Distribution format: tar.gz Programming language: MAPLE R13 Computer: PC Operating system: Windows XP/7 RAM: 2 Gbytes Classification: 4.3 Nature of problem: Solve nonlinear differential equations with initial conditions. Solution method: Adomian decomposition method and Padé technique. Running time: Seconds at most in routine uses of the program. Special tasks may take up to some minutes.

Brain Sexual Differentiation and Requirement of SRY: Why or Why Not?

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Cheryl S. Rosenfeld

2017-11-01

Full Text Available Brain sexual differentiation is orchestrated by precise coordination of sex steroid hormones. In some species, programming of select male brain regions is dependent upon aromatization of testosterone to estrogen. In mammals, these hormones surge during the organizational and activational periods that occur during perinatal development and adulthood, respectively. In various fish and reptiles, incubation temperature during a critical embryonic period results in male or female sexual differentiation, but this can be overridden in males by early exposure to estrogenic chemicals. Testes development in mammals requires a Y chromosome and testis determining gene SRY (in humans/Sry (all other therian mammals, although there are notable exceptions. Two species of spiny rats: Amami spiny rat (Tokudaia osimensis and Tokunoshima spiny rat (Tokudaia tokunoshimensis and two species of mole voles (Ellobius lutescens and Ellobius tancrei, lack a Y chromosome/Sry and possess an XO chromosome system in both sexes. Such rodent species, prototherians (monotremes, who also lack Sry, and fish and reptile species that demonstrate temperature sex determination (TSD seemingly call into question the requirement of Sry for brain sexual differentiation. This review will consider brain regions expressing SRY/Sry in humans and rodents, respectively, and potential roles of SRY/Sry in the brain will be discussed. The evidence from various taxa disputing the requirement of Sry for brain sexual differentiation in mammals (therians and prototherians and certain fish and reptilian species will be examined. A comparative approach to address this question may elucidate other genes, pathways, and epigenetic modifications stimulating brain sexual differentiation in vertebrate species, including humans.

Correlation of initiating potency of skin carcinogens with potency to induce resistance to terminal differentiation in cultured mouse keratinocytes

International Nuclear Information System (INIS)

Kilkenny, A.E.; Morgan, D.; Spangler, E.F.; Yuspa, S.H.

1985-01-01

The induction by chemical carcinogens of resistance to terminal differentiation in cultured mouse keratinocytes has been proposed to represent a cellular change associated with the initiation phase of skin carcinogenesis. Previous results with this culture model indicated that the number of differentiation-resistant foci was correlated with the dose and known potency for several chemical carcinogens. Assay conditions were optimized to provide quantitative results for screening a variety of carcinogens for their potency as inducers of foci resistant to terminal differentiation. Eight skin initiators of varying potency and from different chemical classes and ultraviolet light were studied for their activity to induce this alteration in cultured epidermal cells from newborn BALB/c mice. There was an excellent positive correlation for the potency of these agents as initiators in vivo and as inducers of altered differentiation in vitro. The induction of resistant foci was independent of the relative cytotoxic effects of each agent except where cytotoxicity was extensive and reduced the number of foci. The results support the hypothesis that initiation of carcinogenesis in skin results in an alteration in the program of epidermal cell differentiation. The results also suggest that the assay is useful for identifying relative potency classes (strong, moderate, weak) of initiating agents

A singular initial value problem for some functional differential equations

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Ravi P. Agarwal

2004-01-01

Full Text Available For the initial value problem trx′(t=at+b1x(t+b2x(q1t+b3trx′(q2t+φ(t,x(t,x(q1t,x′(t,x′(q2t, x(0=0, where r>1, 0differentiable solutions x:(0,ρ]→ℝ, each of which possesses nice asymptotic properties when t→+0.

Spectral methods for a nonlinear initial value problem involving pseudo differential operators

International Nuclear Information System (INIS)

Pasciak, J.E.

1982-01-01

Spectral methods (Fourier methods) for approximating the solution of a nonlinear initial value problem involving pseudo differential operators are defined and analyzed. A semidiscrete approximation to the nonlinear equation based on an L 2 projection is described. The semidiscrete L 2 approximation is shown to be a priori stable and convergent under sufficient decay and smoothness assumptions on the initial data. It is shown that the semidiscrete method converges with infinite order, that is, higher order decay and smoothness assumptions imply higher order error bounds. Spectral schemes based on spacial collocation are also discussed

Mind bomb-1 in dendritic cells is specifically required for Notch-mediated T helper type 2 differentiation.

Directory of Open Access Journals (Sweden)

Hyun-Woo Jeong

Full Text Available In dendritic cell (DC-CD4(+ T cell interaction, Notch signaling has been implicated in the CD4(+ T cell activation, proliferation, and subset differentiation. However, there has been a lot of debate on the exact role of Notch signaling. Here, we observed that expression of Mind bomb-1 (Mib1, a critical regulator of Notch ligands for the activation of Notch signaling, increases gradually as precursor cells differentiate into DCs in mice. To clarify the role of Mib1 in DC-CD4(+ T cell interactions, we generated Mib1-null bone marrow-derived DCs. These cells readily expressed Notch ligands but failed to initiate Notch activation in the adjacent cells. Nevertheless, Mib1-null DCs were able to prime the activation and proliferation of CD4(+ T cells, suggesting that Notch activation in CD4(+ T cells is not required for these processes. Intriguingly, stimulation of CD4(+ T cells with Mib1-null DCs resulted in dramatically diminished Th2 cell populations, while preserving Th1 cell populations, both in vitro and in vivo. Our results demonstrate that Mib1 in DCs is critical for the activation of Notch signaling in CD4(+ T cells, and Notch signaling reinforces Th2 differentiation, but is not required for the activation or proliferation of the CD4(+ T cells.

The polycomb group protein Suz12 is required for embryonic stem cell differentiation

DEFF Research Database (Denmark)

Pasini, Diego; Bracken, Adrian P; Hansen, Jacob Bo Højberg

2007-01-01

results in early lethality of mouse embryos. Here, we demonstrate that Suz12(-/-) mouse embryonic stem (ES) cells can be established and expanded in tissue culture. The Suz12(-/-) ES cells are characterized by global loss of H3K27 trimethylation (H3K27me3) and higher expression levels of differentiation......-specific genes. Moreover, Suz12(-/-) ES cells are impaired in proper differentiation, resulting in a lack of repression of ES cell markers as well as activation of differentiation-specific genes. Finally, we demonstrate that the PcGs are actively recruited to several genes during ES cell differentiation, which...... despite an increase in H3K27me3 levels is not always sufficient to prevent transcriptional activation. In summary, we demonstrate that Suz12 is required for the establishment of specific expression programs required for ES cell differentiation. Furthermore, we provide evidence that PcGs have different...

Solving Ordinary Differential Equations

Science.gov (United States)

Krogh, F. T.

1987-01-01

Initial-value ordinary differential equation solution via variable order Adams method (SIVA/DIVA) package is collection of subroutines for solution of nonstiff ordinary differential equations. There are versions for single-precision and double-precision arithmetic. Requires fewer evaluations of derivatives than other variable-order Adams predictor/ corrector methods. Option for direct integration of second-order equations makes integration of trajectory problems significantly more efficient. Written in FORTRAN 77.

Fast and quantitative differentiation of single-base mismatched DNA by initial reaction rate of catalytic hairpin assembly.

Science.gov (United States)

Li, Chenxi; Li, Yixin; Xu, Xiao; Wang, Xinyi; Chen, Yang; Yang, Xiaoda; Liu, Feng; Li, Na

2014-10-15

The widely used catalytic hairpin assembly (CHA) amplification strategy generally needs several hours to accomplish one measurement based on the prevailingly used maximum intensity detection mode, making it less practical for assays where high throughput or speed is desired. To make the best use of the kinetic specificity of toehold domain for circuit reaction initiation, we developed a mathematical model and proposed an initial reaction rate detection mode to quantitatively differentiate the single-base mismatch. Using the kinetic mode, assay time can be reduced substantially to 10 min for one measurement with the comparable sensitivity and single-base mismatch differentiating ability as were obtained by the maximum intensity detection mode. This initial reaction rate based approach not only provided a fast and quantitative differentiation of single-base mismatch, but also helped in-depth understanding of the CHA system, which will be beneficial to the design of highly sensitive and specific toehold-mediated hybridization reactions. Copyright © 2014 Elsevier B.V. All rights reserved.

The Use of Graphs in Specific Situations of the Initial Conditions of Linear Differential Equations

Science.gov (United States)

Buendía, Gabriela; Cordero, Francisco

2013-01-01

In this article, we present a discussion on the role of graphs and its significance in the relation between the number of initial conditions and the order of a linear differential equation, which is known as the initial value problem. We propose to make a functional framework for the use of graphs that intends to broaden the explanations of the…

Initiation of Swarming Motility by Proteus mirabilis Occurs in Response to Specific Cues Present in Urine and Requires Excess l-Glutamine

Science.gov (United States)

Armbruster, Chelsie E.; Hodges, Steven A.

2013-01-01

Proteus mirabilis, a leading cause of catheter-associated urinary tract infection (CaUTI), differentiates into swarm cells that migrate across catheter surfaces and medium solidified with 1.5% agar. While many genes and nutrient requirements involved in the swarming process have been identified, few studies have addressed the signals that promote initiation of swarming following initial contact with a surface. In this study, we show that P. mirabilis CaUTI isolates initiate swarming in response to specific nutrients and environmental cues. Thirty-three compounds, including amino acids, polyamines, fatty acids, and tricarboxylic acid (TCA) cycle intermediates, were tested for the ability to promote swarming when added to normally nonpermissive media. l-Arginine, l-glutamine, dl-histidine, malate, and dl-ornithine promoted swarming on several types of media without enhancing swimming motility or growth rate. Testing of isogenic mutants revealed that swarming in response to the cues required putrescine biosynthesis and pathways involved in amino acid metabolism. Furthermore, excess glutamine was found to be a strict requirement for swarming on normal swarm agar in addition to being a swarming cue under normally nonpermissive conditions. We thus conclude that initiation of swarming occurs in response to specific cues and that manipulating concentrations of key nutrient cues can signal whether or not a particular environment is permissive for swarming. PMID:23316040

Discretizing LTI Descriptor (Regular Differential Input Systems with Consistent Initial Conditions

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Athanasios D. Karageorgos

2010-01-01

Full Text Available A technique for discretizing efficiently the solution of a Linear descriptor (regular differential input system with consistent initial conditions, and Time-Invariant coefficients (LTI is introduced and fully discussed. Additionally, an upper bound for the error ‖x¯(kT−x¯k‖ that derives from the procedure of discretization is also provided. Practically speaking, we are interested in such kind of systems, since they are inherent in many physical, economical and engineering phenomena.

Nonlinear Variation of Parameters Formula for Impulsive Differential Equations with Initial Time Difference and Application

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Peiguang Wang

2014-01-01

Full Text Available This paper establishes variation of parameters formula for impulsive differential equations with initial time difference. As an application, one of the results is used to investigate stability properties of solutions.

Role of hormones in controlling vascular differentiation and the mechanism of lateral root initiation.

Science.gov (United States)

Aloni, Roni

2013-11-01

The vascular system in plants is induced and controlled by streams of inductive hormonal signals. Auxin produced in young leaves is the primary controlling signal in vascular differentiation. Its polar and non-polar transport pathways and major controlling mechanisms are clarified. Ethylene produced in differentiating protoxylem vessels is the signal that triggers lateral root initiation, while tumor-induced ethylene is a limiting and controlling factor of crown gall development and its vascular differentiation. Gibberellin produced in mature leaves moves non-polarly and promotes elongation, regulates cambium activity and induces long fibers. Cytokinin from the root cap moves upward to promote cambial activity and stimulate shoot growth and branching, while strigolactone from the root inhibits branching. Furthermore, the role of the hormonal signals in controlling the type of differentiating vascular elements and gradients of conduit size and density, and how they regulate plant adaptation and have shaped wood evolution are elucidated.

Au Contraire: Differentiation Requires HOPE

Science.gov (United States)

Delisle, James R.

2002-01-01

Everybody is doing it: differentiating curriculum to make it deeper, broader, parallel, and more complex. No longer the private property of gifted specialists, differentiation is now a democratic pursuit of classroom teachers, curriculum specialists, and anyone else who subscribes to "Educational Leadership." In an era of competency-based tests…

Electromyographic Pattern during Gait Initiation Differentiates Yoga Practitioners among Physically Active Older Subjects

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Thierry Lelard

2017-06-01

Full Text Available During gait initiation, postural adjustments are needed to deal with balance and movement. With aging, gait initiation changes and reflects functional degradation of frailty individuals. However, physical activities have demonstrated beneficial effects of daily motor tasks. The aim of our study was to compare center of pressure (COP displacement and ankle muscle co-activation during gait initiation in two physically active groups: a group of walkers (n = 12; mean age ± SD 72.6 ± 3.2 years and a yoga group (n = 11; 71.5 ± 3.8 years. COP trajectory and electromyography of leg muscles were recorded simultaneously during five successive trials of gait initiation. Our main finding was that yoga practitioners had slower COP displacements (p < 0.01 and lower leg muscles % of coactivation (p < 0.01 in comparison with walkers. These parameters which characterized gait initiation control were correlated (r = 0.76; p < 0.01. Our results emphasize that lengthy ankle muscle co-activation and COP path in gait initiation differentiate yoga practitioners among physically active subjects.

Application of the variational iteration method for system of initial value problems delay differential equations

Science.gov (United States)

Yousef, Hamood. M.; Ismail, A. I. B. MD.

2017-08-01

Many attempts have been presented to solve the system of Delay Differential Equations (DDE) with Initial Value Problem. As a result, it has shown difficulties when getting the solution or cannot be solved. In this paper, a Variational Iteration Method is employed to find out an approximate solution for the system of DDE with initial value problems. The example illustrates convenient and an efficiency comparison with the exact solution.

Regulation of eukaryotic initiation factor 4AII by MyoD during murine myogenic cell differentiation.

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Gabriela Galicia-Vázquez

Full Text Available Gene expression during muscle cell differentiation is tightly regulated at multiple levels, including translation initiation. The PI3K/mTOR signalling pathway exerts control over protein synthesis by regulating assembly of eukaryotic initiation factor (eIF 4F, a heterotrimeric complex that stimulates recruitment of ribosomes to mRNA templates. One of the subunits of eIF4F, eIF4A, supplies essential helicase function during this phase of translation. The presence of two cellular eIF4A isoforms, eIF4AI and eIF4AII, has long thought to impart equivalent functions to eIF4F. However, recent experiments have alluded to distinct activities between them. Herein, we characterize distinct regulatory mechanisms between the eIF4A isoforms during muscle cell differentiation. We find that eIF4AI levels decrease during differentiation whereas eIF4AII levels increase during myofiber formation in a MyoD-dependent manner. This study characterizes a previously undefined mechanism for eIF4AII regulation in differentiation and highlights functional differences between eIF4AI and eIF4AII. Finally, RNAi-mediated alterations in eIF4AI and eIF4AII levels indicate that the myogenic process can tolerate short term reductions in eIF4AI or eIF4AII levels, but not both.

Adenoviral DNA replication: DNA sequences and enzymes required for initiation in vitro

International Nuclear Information System (INIS)

Stillman, B.W.; Tamanoi, F.

1983-01-01

In this paper evidence is provided that the 140,000-dalton DNA polymerase is encoded by the adenoviral genome and is required for the initiation of DNA replication in vitro. The DNA sequences in the template DNA that are required for the initiation of replication have also been identified, using both plasmid DNAs and synthetic oligodeoxyribonucleotides. 48 references, 7 figures, 1 table

40 CFR 63.11584 - What are my initial and continuous compliance management practice requirements?

Science.gov (United States)

2010-07-01

... compliance management practice requirements? 63.11584 Section 63.11584 Protection of Environment... What are my initial and continuous compliance management practice requirements? (a) For each new and... gr/dscf, the management practice requirements are as follows: (1) You must conduct an initial visual...

Inhomogeneous Linear Random Differential Equations with Mutual Correlations between Multiplicative, Additive and Initial-Value Terms

NARCIS (Netherlands)

Roerdink, J.B.T.M.

1981-01-01

The cumulant expansion for linear stochastic differential equations is extended to the general case in which the coefficient matrix, the inhomogeneous part and the initial condition are all random and, moreover, statistically interdependent. The expansion now involves not only the autocorrelation

Uplink Cross-Layer Scheduling with Differential QoS Requirements in OFDMA Systems

Directory of Open Access Journals (Sweden)

Chen Wei

2010-01-01

Full Text Available Fair and efficient scheduling is a key issue in cross-layer design for wireless communication systems, such as 3GPP LTE and WiMAX. However, few works have considered the multiaccess of the traffic with differential QoS requirements in wireless systems. In this paper, we will consider an OFDMA-based wireless system with four types of traffic associated with differential QoS requirements, namely, minimum reserved rate, maximum sustainable rate, maximum latency, and tolerant jitter. Given these QoS requirements, the traffic scheduling will be formulated into a cross-layer optimization problem, which is convex fortunately. By separating the power allocation through the waterfilling algorithm in each user, this problem will further reduce to a kind of continuous quadratic knapsack problem in the base station which yields low complexity. It is then demonstrated that the proposed cross-layer method cannot only guarantee the application layer QoS requirements, but also minimizes the integrated residual workload in the MAC layer. To further enhance the ability of QoS assurance in heavily loaded scenario, a call admission control scheme will also be proposed. The simulation results show that the QoS requirements for the four types of traffic are guaranteed effectively by the proposed algorithms.

Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts.

Science.gov (United States)

Sin, Jon; Andres, Allen M; Taylor, David J R; Weston, Thomas; Hiraumi, Yoshimi; Stotland, Aleksandr; Kim, Brandon J; Huang, Chengqun; Doran, Kelly S; Gottlieb, Roberta A

2016-01-01

Myogenesis is a crucial process governing skeletal muscle development and homeostasis. Differentiation of primitive myoblasts into mature myotubes requires a metabolic switch to support the increased energetic demand of contractile muscle. Skeletal myoblasts specifically shift from a highly glycolytic state to relying predominantly on oxidative phosphorylation (OXPHOS) upon differentiation. We have found that this phenomenon requires dramatic remodeling of the mitochondrial network involving both mitochondrial clearance and biogenesis. During early myogenic differentiation, autophagy is robustly upregulated and this coincides with DNM1L/DRP1 (dynamin 1-like)-mediated fragmentation and subsequent removal of mitochondria via SQSTM1 (sequestosome 1)-mediated mitophagy. Mitochondria are then repopulated via PPARGC1A/PGC-1α (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha)-mediated biogenesis. Mitochondrial fusion protein OPA1 (optic atrophy 1 [autosomal dominant]) is then briskly upregulated, resulting in the reformation of mitochondrial networks. The final product is a myotube replete with new mitochondria. Respirometry reveals that the constituents of these newly established mitochondrial networks are better primed for OXPHOS and are more tightly coupled than those in myoblasts. Additionally, we have found that suppressing autophagy with various inhibitors during differentiation interferes with myogenic differentiation. Together these data highlight the integral role of autophagy and mitophagy in myogenic differentiation.

Differential requirements of androgen receptor in luminal progenitors during prostate regeneration and tumor initiation

Science.gov (United States)

Chua, Chee Wai; Epsi, Nusrat J; Leung, Eva Y; Xuan, Shouhong; Lei, Ming; Li, Bo I; Bergren, Sarah K; Hibshoosh, Hanina; Mitrofanova, Antonina

2018-01-01

Master regulatory genes of tissue specification play key roles in stem/progenitor cells and are often important in cancer. In the prostate, androgen receptor (AR) is a master regulator essential for development and tumorigenesis, but its specific functions in prostate stem/progenitor cells have not been elucidated. We have investigated AR function in CARNs (CAstration-Resistant Nkx3.1-expressing cells), a luminal stem/progenitor cell that functions in prostate regeneration. Using genetically--engineered mouse models and novel prostate epithelial cell lines, we find that progenitor properties of CARNs are largely unaffected by AR deletion, apart from decreased proliferation in vivo. Furthermore, AR loss suppresses tumor formation after deletion of the Pten tumor suppressor in CARNs; however, combined Pten deletion and activation of oncogenic Kras in AR-deleted CARNs result in tumors with focal neuroendocrine differentiation. Our findings show that AR modulates specific progenitor properties of CARNs, including their ability to serve as a cell of origin for prostate cancer. PMID:29334357

Hanford Tanks Initiative requirements and document management process guide

International Nuclear Information System (INIS)

Schaus, P.S.

1998-01-01

This revision of the guide provides updated references to project management level Program Management and Assessment Configuration Management activities, and provides working level directions for submitting requirements and project documentation related to the Hanford Tanks Initiative (HTI) project. This includes documents and information created by HTI, as well as non-HTI generated materials submitted to the project

An algorithm for solving initial value problems of third order ordinary ...

African Journals Online (AJOL)

Abstract. We propose an implicit multi-step method for the solution of initial value problems (IVPs) of third order ordinary differential equations (ODE) which does not require reducing the ODE to first order before solving. The development of the method is based on collocation of the differential system and interpolation of the ...

The potential role of ribosomal protein S5 on cell cycle arrest and initiation of murine erythroleukemia cell differentiation.

Science.gov (United States)

Matragkou, Christina N; Papachristou, Eleni T; Tezias, Sotirios S; Tsiftsoglou, Asterios S; Choli-Papadopoulou, Theodora; Vizirianakis, Ioannis S

2008-07-01

Evidence now exists to indicate that some ribosomal proteins besides being structural components of the ribosomal subunits are involved in the regulation of cell differentiation and apoptosis. As we have shown earlier, initiation of erythroid differentiation of murine erythroleukemia (MEL) cells is associated with transcriptional inactivation of genes encoding ribosomal RNAs and ribosomal proteins S5 (RPS5) and L35a. In this study, we extended these observations and investigated whether transfection of MEL cells with RPS5 cDNA affects the onset of initiation of erythroid maturation and their entrance in cell cycle arrest. Stably transfected MEL cloned cells (MEL-C14 and MEL-C56) were established and assessed for their capacity to produce RPS5 RNA transcript and its translated product. The impact of RPS5 cDNA transfection on the RPS5 gene expression patterns and the accumulation of RPS5 protein in inducible transfected MEL cells were correlated with their ability to: (a) initiate differentiation, (b) enter cell cycle arrest at G(1)/G(0) phase, and (c) modulate the level of cyclin-dependent kinases CDK2, CDK4, and CDK6. The data presented indicate that deregulation of RPS5 gene expression (constitutive expression) affects RPS5 protein level and delays both the onset of initiation of erythroid maturation and entrance in cell cycle arrest in inducer-treated MEL cells. 2008 Wiley-Liss, Inc.

Differentiation, context and teacher education: the changing profile of trainees on in-service initial teacher training programmes in the lifelong learning sector

Directory of Open Access Journals (Sweden)

Noel, Penny

2009-01-01

Full Text Available Analysis of initial teacher training (ITT student data relating to the University of Huddersfield part-time in-service Cert Ed/PGCE over a three-year period has revealed significant change in the make-up of trainee cohorts. There has been an increase in younger trainees and in trainees very new to teaching, although more experienced and older trainees do continue to enrol. There has also been a considerable shift in the balance of trainees away from further education (FE college staff. These changes have implications for those who manage and deliver teacher education for the sector. It remains of key importance that the curriculum is not experienced as overly ‘FE-college centric’ and that mentoring arrangements acknowledge the needs of trainees from diverse contexts. It is clear that in the delivery of ITT for the lifelong learning sector, increasingly, one size will not comfortably fit all. Within teacher education much emphasis is placed upon the role of differentiation in regard to trainee practice. The changing trainee profile identified requires that teacher education itself unambiguously models a differentiated approach – and, in relation to teacher education for the lifelong learning sector, differentiation must address workplace context.

Assessment of available integration algorithms for initial value ordinary differential equations

International Nuclear Information System (INIS)

Carver, M.B.; Stewart, D.G.

1979-11-01

There exists an extremely large number of algorithms designed for the ordinary differential equation initial value problem. The integration is normally done by a finite sum at time intervals which are chosen dynamically to satisfy an imposed error tolerance. This report describes the basic logistics of the integration process, identifies common areas of difficulty, and establishes a comprehensive test profile for integration algorithms. A number of algorithms are described, and selected published subroutines are evaluated using the test profile. It concludes that an effective library for general use need have only two such routines. The two selected are versions of the well-known Gear and Runge-Kutta-Fehlberg algorithms. Full documentation and listings are included. (auth)

Differentiation of initial skills in 1st grade and the relative age effect in 3rd grade

Directory of Open Access Journals (Sweden)

KRZYSZTOF KONARZEWSKI

2017-06-01

Full Text Available The paper aims to verify two hypotheses. The first states that the differentiation of initial 1st grade pupil skills is negatively correlated with age at entry to school. This was tested according to findings from the ERI study Six and seven year olds at the start of school. The variation of reading and writing scores of 1164 pupils aged 5.9–7.9 years who were beginning 1st grade decreased in subsequent age quartiles. The second hypothesis – that classroom differentiation of pupils’ initial skills in 1st grade is positively correlated with the birthdate effect in 3rd grade – was tested on data of 4838 pupils from 254 classrooms drawn from the 2011 PIRLS and TIMSS studies in Poland. Skills were evaluated on the basis of parental reports. Hierarchical linear analysis (gender, SES and school location controlled showed that the greater the differentiation of language skills in 1st grade, the greater the birthdate effect in mathematics in 3rd grade. This result suggests that school entry age is of lesser importance than the methods used to reduce differences in children’s school readiness at the onset of education.

Prognostic factors of a good response to initial therapy in children and adolescents with differentiated thyroid cancer

Directory of Open Access Journals (Sweden)

Fernanda Vaisman

2011-01-01

Full Text Available BACKGROUND: Therapeutic approaches in pediatric populations are based on adult data because there is a lack of appropriate data for children. Consequently, there are many controversies regarding the proper treatment of pediatric patients. OBJECTIVE: The present study was designed to evaluate patients with differentiated thyroid carcinoma diagnosed before 20 years of age and to determine the factors associated with the response to the initial therapy. METHODS: Sixty-five patients, treated in two tertiary-care referral centers in Rio de Janeiro between 1980 and 2005 were evaluated. Information about clinical presentation and the response to initial treatment was analyzed and patients had their risk stratified in Tumor-Node- Metastasis; Age-Metastasis-Extracapsular-Size; distant Metastasis-Age-Completeness of primary tumor resection-local Invasion-Size and American-Thyroid-Association classification RESULTS: Patients ages ranged from 4 to 20 years (median 14. The mean follow-up was 12,6 years. Lymph node metastasis was found in 61.5% and indicated a poor response to initial therapy, with a significant impact on time for achieving disease free status (p = 0.014 for response to initial therapy and p<0,0001 for disease-free status in follow-up. Distant metastasis was a predictor of a poor response to initial therapy in these patients (p = 0.014. The risk stratification systems we analyzed were useful for high-risk patients because they had a high sensitivity and negative predictive value in determining the response to initial therapy. CONCLUSIONS: Metastases, both lymph nodal and distant, are important predictors of the persistence of disease after initial therapy in children and adolescents with differentiated thyroid cancer.

Making the Grade: Describing Inherent Requirements for the Initial Teacher Education Practicum

Science.gov (United States)

Sharplin, Elaine; Peden, Sanna; Marais, Ida

2016-01-01

This study explores the development, description, and illustration of inherent requirement (IR) statements to make explicit the requirements for performance on an initial teacher education (ITE) practicum. Through consultative group processes with stakeholders involved in ITE, seven IR domains were identified. From interviews with academics,…

Study of Bud Differentiation in Hayward and Tomuri Cultivars of Kiwifruit

Directory of Open Access Journals (Sweden)

Ebrahim Abedi gheshlaghi

2017-12-01

, about one month before bud break in 2015. While in the Hayward variety the first signs of the flower primordia were observed on the March 21th of 2015 (9 days later. At the beginning of bud swelling (01, flower primordia begin to differentiation and at advanced bud swelling stage (03, bracts and sepals initiated. As development proceeded, different parts of flowers initiated acropetally. Lateral flowers were formed in the bud break (07, before initiation of petals. In advanced budburst stage (09 stamen primordia appear almost immediately after petal initiation, as two whorls in 'Hayward' and as three whorls in the Tomuri cultivar. Stigma initiated in the open cluster stage (10 in Hayward cultivar about 24-25 days after bud swell stage. The process of differentiation of buds and reproductive organs in the second year was the same as the first year with the exception that differentiation began earlier than that in the first year. Climatic conditions were affected flower development and in the second year primordia differentiation began earlier two days in Tomuri and six days in Hayward than those in the first year. The advanced budburst stage (09 in Tomuri 9 days and in the Hayward 10 days was occurred earlier than that in the first year. Unlike other tree fruits, flower induction in the kiwifruit occurred about 6 months before flower initiation. Flower primordia differentiation initiated shortly before bud break stage and approximately two months before full bloom. Flower initiation and differentiation time may be partly estimated with external changes of buds development. According to cultivar, chilling and heat requirements and climatic conditions during the research, flower initiation and differentiation period have fluctuation. A reason for the difference between the development stages and different varieties can be caused by the chilling and heat requirements. The more heat requirement, the longer reproductive meristem differentiation period. Conclusion: An

Progress towards initiation of somatic embryogenesis from differentiated tissues of radiata pine (Pinus radiata D. Don) using cotyledonary embryos

DEFF Research Database (Denmark)

Find, Jens Iver; Hargreaves, Cathy L.; Reeves, Catherine B.

2014-01-01

of dissected embryos and a modified Litvay medium, Glitz, was best. This combination gave the highest rate of initiation, and it was possible to initiate somatic embryogenesis (SE) from differentiated cells in the epicotyledonary region of postcotyledonary zygotic embryos from the two tested families...... with an average initiation rate of approximately 24% and 7% from stage five and six embryos, respectively. This is different from established initiation protocols of embryogenic cultures in radiata pine, which has traditionally been based on embryo rescue and continued proliferation of immature zygotic embryos....... A further implication of initiation of SE from excised post-cotyledonary embryos was that the period of initiation of embryogenic cultures was extended from 4 to 12 wk....

A differential equation approach to minor loops in the Jiles-Atherton hysteresis model

International Nuclear Information System (INIS)

Carpenter, K.H.

1991-01-01

Jiles and Atherton, in a series of papers, present physically based differential equations for magnetization in ferromagnetic materials. however, if one directly solves their differential equations, the minor loops obtained can be negative slopes, which is a nonphysical behavior. Only one of their papers gives a method for obtaining minor loops, and the method does not use a differential equation, but requires a priori knowledge of the loop turning points in order to obtain a scale factor and offset which allow a portion of a major loop to serve as a portion of a minor one. In this paper, the reason for the failure of the differential equations to yield physical minor loops is explained, and a modified solution for minor loops is presented which retains the features of Jiles and Atherton's original minor loops, but only requires knowledge of the initial point on each portion of the loop to obtain the solution. This yields a general differential equation formulation for the Jiles-Atherton theory that can be used with circuit simulations having arbitrary excitations and initial conditions for ferromagnetic components

Optimal Error Estimates of Two Mixed Finite Element Methods for Parabolic Integro-Differential Equations with Nonsmooth Initial Data

KAUST Repository

Goswami, Deepjyoti; Pani, Amiya K.; Yadav, Sangita

2013-01-01

In the first part of this article, a new mixed method is proposed and analyzed for parabolic integro-differential equations (PIDE) with nonsmooth initial data. Compared to the standard mixed method for PIDE, the present method does not bank on a

Stochastic differential equtions with non-lipschitz coefficients:II. Dependence with respect to initial values

OpenAIRE

Fang, Shizan; Zhang, Tusheng

2003-01-01

14 pages; The existence of the unique strong solution for a class of stochastic differential equations with non-Lipschitz coefficients was established recently. In this paper, we shall investigate the dependence with respect to the initial values. We shall prove that the non confluence of solutions holds under our general conditions. To obtain a continuous version, the modulus of continuity of coefficients is assumed to be less than $\\dis |x-y|\\log{1\\over|x-y|}$. In this case, it will give ri...

Low concentrations of ketamine initiate dendritic atrophy of differentiated GABAergic neurons in culture

International Nuclear Information System (INIS)

Vutskits, Laszlo; Gascon, Eduardo; Potter, Gael; Tassonyi, Edomer; Kiss, Jozsef Z.

2007-01-01

Administration of subanesthetic concentrations of ketamine, a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) type of glutamate receptors, is a widely accepted therapeutic modality in perioperative and chronic pain management. Although extensive clinical use has demonstrated its safety, recent human histopathological observations as well as laboratory data suggest that ketamine can exert adverse effects on central nervous system neurons. To further investigate this issue, the present study was designed to evaluate the effects of ketamine on the survival and dendritic arbor architecture of differentiated γ-aminobutyric acidergic (GABAergic) interneurons in vitro. We show that short-term exposure of cultures to ketamine at concentrations of ≥20 μg/ml leads to a significant cell loss of differentiated cells and that non-cell death-inducing concentrations of ketamine (10 μg/ml) can still initiate long-term alterations of dendritic arbor in differentiated neurons, including dendritic retraction and branching point elimination. Most importantly, we also demonstrate that chronic (>24 h) administration of ketamine at concentrations as low as 0.01 μg/ml can interfere with the maintenance of dendritic arbor architecture. These results raise the possibility that chronic exposure to low, subanesthetic concentrations of ketamine, while not affecting cell survival, could still impair neuronal morphology and thus might lead to dysfunctions of neural networks

Graduated diagnostics required. Broad spectrum of differential diagnoses

International Nuclear Information System (INIS)

Auer, I.O.

1997-01-01

The time lapse between initial symptoms and secured diagnosis of colitis ulcerosa still is 6-8 weeks, in case of M. Crohn even about 30 weeks. A graduated diagnostic approach is required: phase 1 relies on non-invasive methods such as anamnesis, physical examination, examination of stools, blood chemistry and sonography of the abdomen; phase 2 ecompasses endoscopy and radiological techniques, phase 3 computed tomography and MRI for detection of complications. The results of the leucodiagnosis by scintiscanning, for detection of inflammations of and out of the intestine, offer a still inhomogenous picture in terms of sensitivity and specificity. (orig./MG) [de

Action potential generation requires a high sodium channel density in the axon initial segment

NARCIS (Netherlands)

Kole, Maarten H. P.; Ilschner, Susanne U.; Kampa, Björn M.; Williams, Stephen R.; Ruben, Peter C.; Stuart, Greg J.

2008-01-01

The axon initial segment ( AIS) is a specialized region in neurons where action potentials are initiated. It is commonly assumed that this process requires a high density of voltage-gated sodium ( Na(+)) channels. Paradoxically, the results of patch-clamp studies suggest that the Na(+) channel

Two pore channel 2 differentially modulates neural differentiation of mouse embryonic stem cells.

Directory of Open Access Journals (Sweden)

Zhe-Hao Zhang

Full Text Available Nicotinic acid adenine dinucleotide phosphate (NAADP is an endogenous Ca(2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca(2+ from acidic organelles through two pore channel 2 (TPC2 in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation.

BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

International Nuclear Information System (INIS)

Goupille, Olivier; Penglong, Tipparat; Lefèvre, Carine; Granger, Marine; Kadri, Zahra; Fucharoen, Suthat; Maouche-Chrétien, Leila; Leboulch, Philippe; Chrétien, Stany

2012-01-01

Highlights: ► UT7 erythroleukemia cells are known to be refractory to differentiate. ► Brief JQ1 treatment initiates the first steps of erythroid differentiation program. ► Engaged UT7 cells then maturate in the presence of erythropoietin. ► Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

BET bromodomain inhibition rescues erythropoietin differentiation of human erythroleukemia cell line UT7

Energy Technology Data Exchange (ETDEWEB)

Goupille, Olivier [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Penglong, Tipparat [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Lefevre, Carine; Granger, Marine; Kadri, Zahra [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Fucharoen, Suthat [Thalassemia Research Center and Department of Clinical Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (Thailand); Maouche-Chretien, Leila [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Leboulch, Philippe [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France); Genetics Division, Department of Medicine, Brigham and Women' s Hospital and Harvard Medical School, Boston, MA (United States); Chretien, Stany, E-mail: stany.chretien@cea.fr [CEA, Institute of Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses (France); UMR INSERM U.962, University Paris XI, CEA, Fontenay-aux-Roses (France)

2012-12-07

Highlights: Black-Right-Pointing-Pointer UT7 erythroleukemia cells are known to be refractory to differentiate. Black-Right-Pointing-Pointer Brief JQ1 treatment initiates the first steps of erythroid differentiation program. Black-Right-Pointing-Pointer Engaged UT7 cells then maturate in the presence of erythropoietin. Black-Right-Pointing-Pointer Sustained JQ1 treatment inhibits both proliferation and erythroid differentiation. -- Abstract: Malignant transformation is a multistep process requiring oncogenic activation, promoting cellular proliferation, frequently coupled to inhibition of terminal differentiation. Consequently, forcing the reengagement of terminal differentiation of transformed cells coupled or not with an inhibition of their proliferation is a putative therapeutic approach to counteracting tumorigenicity. UT7 is a human leukemic cell line able to grow in the presence of IL3, GM-CSF and Epo. This cell line has been widely used to study Epo-R/Epo signaling pathways but is a poor model for erythroid differentiation. We used the BET bromodomain inhibition drug JQ1 to target gene expression, including that of c-Myc. We have shown that only 2 days of JQ1 treatment was required to transitory inhibit Epo-induced UT7 proliferation and to restore terminal erythroid differentiation. This study highlights the importance of a cellular erythroid cycle break mediated by c-Myc inhibition before initiation of the erythropoiesis program and describes a new model for BET bromodomain inhibitor drug application.

Comparison of initial capital investment requirements for new domestic energy supplies: 1980 update

International Nuclear Information System (INIS)

Schlesinger, B.; Hay, N.E.; Wilkinson, P.

1980-01-01

A.G.A.'s update of its 1978 analysis comparing the initial capital investments required for several domestic sources of alternative energy (coal conversion, oil shale, unconventional natural gas, Alaskan gas, nuclear power, and solar energy) concludes that US energy-supply and utilization systems based on gaseous fuels need substantially less initial capital investment than do equivalent nuclear, coal, and solar electric systems or synthetic-liquids systems. The capital estimates include the costs of resource extraction, processing and conversion, transmission and distribution, and end-use equipment. The cost advantages shown for the three end-use applications compared - residential and small-commercial space heating, premium industrial usage, and large industrial boilers - reflect both the lower capital requirements and higher energy efficiencies of the gaseous systems

Functional requirements of cellular differentiation: lessons from Bacillus subtilis.

Science.gov (United States)

Narula, Jatin; Fujita, Masaya; Igoshin, Oleg A

2016-12-01

Successful execution of differentiation programs requires cells to assess multitudes of internal and external cues and respond with appropriate gene expression programs. Here, we review how Bacillus subtilis sporulation network deals with these tasks focusing on the lessons generalizable to other systems. With feedforward loops controlling both production and activation of downstream transcriptional regulators, cells achieve ultrasensitive threshold-like responses. The arrangement of sporulation network genes on the chromosome and transcriptional feedback loops allow coordination of sporulation decision with DNA-replication. Furthermore, to assess the starvation conditions without sensing specific metabolites, cells respond to changes in their growth rates with increased activity of sporulation master regulator. These design features of the sporulation network enable cells to robustly decide between vegetative growth and sporulation. Copyright © 2016 Elsevier Ltd. All rights reserved.

Preliminary design requirements document (DRD) for Project W-236B, ''Initial Pretreatment Module''

International Nuclear Information System (INIS)

Swanson, L.M.

1995-01-01

The scope of this Design Requirements Document (DRD) is to identify and define the functions, with associated requirements, which must be performed to separate Hanford Site tank waste supernatants into low-level and high-level fractions. This documents sets forth function requirements, performance requirements, and design constraints necessary to begin conceptual design for the Initial Pretreatment Module (IPM). System and physical interfaces between the IPM project and the Tank Waste Remediation System (TWRS) are identified. The constraints, performance requirements, and transfer of information and data across a technical interface will be documented in an Interface Control Document. Supplemental DRDs will be prepared to provide more detailed requirements specific to systems described in the DRD

Comparison of the inertial properties and forces required to initiate movement for three gait trainers.

Science.gov (United States)

Paleg, Ginny; Huang, Morris; Vasquez Gabela, Stephanie C; Sprigle, Stephen; Livingstone, Roslyn

2016-01-01

The purpose of this study was to evaluate the inertial properties and forces required to initiate movement on two different surfaces in a sample of three commonly prescribed gait trainers. Tests were conducted in a laboratory setting to compare the Prime Engineering KidWalk, Rifton Pacer, and Snug Seat Mustang with and without a weighted anthropometric test dummy configured to the weight and proportions of a 4-year-old child. The Pacer was the lightest and the KidWalk the heaviest while footprints of the three gait trainers were similar. Weight was borne fairly evenly on the four casters of the Pacer and Mustang while 85% of the weight was borne on the large wheels of the mid-wheel drive KidWalk. These differences in frame style, wheel, and caster style and overall mass impact inertial properties and forces required to initiate movement. Test results suggest that initiation forces on tile were equivalent for the Pacer and KidWalk while the Mustang had the highest initiation force. Initiation forces on carpet were lowest for the KidWalk and highest for the Mustang. This initial study of inertia and movement initiation forces may provide added information for clinicians to consider when selecting a gait trainer for their clients.

Paralogous SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) genes differentially regulate leaf initiation and reproductive phase change in petunia.

Science.gov (United States)

Preston, Jill C; Jorgensen, Stacy A; Orozco, Rebecca; Hileman, Lena C

2016-02-01

Duplicated petunia clade-VI SPL genes differentially promote the timing of inflorescence and flower development, and leaf initiation rate. The timing of plant reproduction relative to favorable environmental conditions is a critical component of plant fitness, and is often associated with variation in plant architecture and habit. Recent studies have shown that overexpression of the microRNA miR156 in distantly related annual species results in plants with perennial characteristics, including late flowering, weak apical dominance, and abundant leaf production. These phenotypes are largely mediated through the negative regulation of a subset of genes belonging to the SQUAMOSA PROMOTER BINDING PROTEIN-LIKE (SPL) family of transcription factors. In order to determine how and to what extent paralogous SPL genes have partitioned their roles in plant growth and development, we functionally characterized petunia clade-VI SPL genes under different environmental conditions. Our results demonstrate that PhSBP1and PhSBP2 differentially promote discrete stages of the reproductive transition, and that PhSBP1, and possibly PhCNR, accelerates leaf initiation rate. In contrast to the closest homologs in annual Arabidopsis thaliana and Mimulus guttatus, PhSBP1 and PhSBP2 transcription is not mediated by the gibberellic acid pathway, but is positively correlated with photoperiod and developmental age. The developmental functions of clade-VI SPL genes have, thus, evolved following both gene duplication and speciation within the core eudicots, likely through differential regulation and incomplete sub-functionalization.

A mex3 homolog is required for differentiation during planarian stem cell lineage development

Science.gov (United States)

Zhu, Shu Jun; Hallows, Stephanie E; Currie, Ko W; Xu, ChangJiang; Pearson, Bret J

2015-01-01

Neoblasts are adult stem cells (ASCs) in planarians that sustain cell replacement during homeostasis and regeneration of any missing tissue. While numerous studies have examined genes underlying neoblast pluripotency, molecular pathways driving postmitotic fates remain poorly defined. In this study, we used transcriptional profiling of irradiation-sensitive and irradiation-insensitive cell populations and RNA interference (RNAi) functional screening to uncover markers and regulators of postmitotic progeny. We identified 32 new markers distinguishing two main epithelial progenitor populations and a planarian homolog to the MEX3 RNA-binding protein (Smed-mex3-1) as a key regulator of lineage progression. mex3-1 was required for generating differentiated cells of multiple lineages, while restricting the size of the stem cell compartment. We also demonstrated the utility of using mex3-1(RNAi) animals to identify additional progenitor markers. These results identified mex3-1 as a cell fate regulator, broadly required for differentiation, and suggest that mex3-1 helps to mediate the balance between ASC self-renewal and commitment. DOI: http://dx.doi.org/10.7554/eLife.07025.001 PMID:26114597

77 FR 59418 - Notice of Initial Determination Revising the List of Products Requiring Federal Contractor...

Science.gov (United States)

2012-09-27

... of products requiring federal contractor certification as to the use of forced or indentured child... DEPARTMENT OF LABOR Notice of Initial Determination Revising the List of Products Requiring Federal Contractor Certification as to Forced/Indentured Child Labor Pursuant to Executive Order 13126...

76 FR 61384 - Notice of Initial Determination Revising the List of Products Requiring Federal Contractor...

Science.gov (United States)

2011-10-04

... Maintenance of the List of Products Requiring Federal Contractor Certification as to Forced or Indentured... DEPARTMENT OF LABOR Notice of Initial Determination Revising the List of Products Requiring Federal Contractor Certification as to Forced/Indentured Child Labor Pursuant to Executive Order 13126...

Initiation of DNA replication requires actin dynamics and formin activity.

Science.gov (United States)

Parisis, Nikolaos; Krasinska, Liliana; Harker, Bethany; Urbach, Serge; Rossignol, Michel; Camasses, Alain; Dewar, James; Morin, Nathalie; Fisher, Daniel

2017-11-02

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms. © 2017 The Authors.

A necessary and sufficient condition for well-posedness of initial value problems of retarded functional differential equations

Science.gov (United States)

Nishiguchi, Junya

2017-09-01

We introduce the retarded functional differential equations (RFDEs) with general delay structure to treat various delay differential equations (DDEs) in a unified way and to clarify the delay structure in those dynamics. We are interested in the question as to which space of histories is suitable for the dynamics of each DDE, and investigate the well-posedness of the initial value problems (IVPs) of the RFDEs. A main theorem is that the IVP is well-posed for any ;admissible; history functional if and only if the semigroup determined by the trivial RFDE x ˙ = 0 is continuous. We clarify the meaning of the Hale-Kato axiom (Hale & Kato [12]) by applying this result to RFDEs with infinite delay. We also apply the result to DDEs with unbounded time- and state-dependent delays.

Neural substrate of initiation of cross-modal working memory retrieval.

Directory of Open Access Journals (Sweden)

Yangyang Zhang

Full Text Available Cross-modal working memory requires integrating stimuli from different modalities and it is associated with co-activation of distributed networks in the brain. However, how brain initiates cross-modal working memory retrieval remains not clear yet. In the present study, we developed a cued matching task, in which the necessity for cross-modal/unimodal memory retrieval and its initiation time were controlled by a task cue appeared in the delay period. Using functional magnetic resonance imaging (fMRI, significantly larger brain activations were observed in the left lateral prefrontal cortex (l-LPFC, left superior parietal lobe (l-SPL, and thalamus in the cued cross-modal matching trials (CCMT compared to those in the cued unimodal matching trials (CUMT. However, no significant differences in the brain activations prior to task cue were observed for sensory stimulation in the l-LPFC and l-SPL areas. Although thalamus displayed differential responses to the sensory stimulation between two conditions, the differential responses were not the same with responses to the task cues. These results revealed that the frontoparietal-thalamus network participated in the initiation of cross-modal working memory retrieval. Secondly, the l-SPL and thalamus showed differential activations between maintenance and working memory retrieval, which might be associated with the enhanced demand for cognitive resources.

Neural substrate of initiation of cross-modal working memory retrieval.

Science.gov (United States)

Zhang, Yangyang; Hu, Yang; Guan, Shuchen; Hong, Xiaolong; Wang, Zhaoxin; Li, Xianchun

2014-01-01

Cross-modal working memory requires integrating stimuli from different modalities and it is associated with co-activation of distributed networks in the brain. However, how brain initiates cross-modal working memory retrieval remains not clear yet. In the present study, we developed a cued matching task, in which the necessity for cross-modal/unimodal memory retrieval and its initiation time were controlled by a task cue appeared in the delay period. Using functional magnetic resonance imaging (fMRI), significantly larger brain activations were observed in the left lateral prefrontal cortex (l-LPFC), left superior parietal lobe (l-SPL), and thalamus in the cued cross-modal matching trials (CCMT) compared to those in the cued unimodal matching trials (CUMT). However, no significant differences in the brain activations prior to task cue were observed for sensory stimulation in the l-LPFC and l-SPL areas. Although thalamus displayed differential responses to the sensory stimulation between two conditions, the differential responses were not the same with responses to the task cues. These results revealed that the frontoparietal-thalamus network participated in the initiation of cross-modal working memory retrieval. Secondly, the l-SPL and thalamus showed differential activations between maintenance and working memory retrieval, which might be associated with the enhanced demand for cognitive resources.

ODEPACK, Initial Value Problems of Ordinary Differential Equation System

International Nuclear Information System (INIS)

Hindmarsh, A.C.; Petzold, L.R.

2005-01-01

I - Description of program or function: ODEPACK is a collection of Fortran solvers for the initial value problem for ordinary differential equation systems. It consists of nine solvers, namely a basic solver called LSODE and eight variants of it -- LSODES, LSODA, LSODAR, LSODPK, LSODKR, LSODI, LSOIBT, and LSODIS. The collection is suitable for both stiff and non-stiff systems. It includes solvers for systems given in explicit form, dy/dt = f(t,y), and also solvers for systems given in linearly implicit form, A(t,y) dy/dt = g(t,y). Two of the solvers use general sparse matrix solvers for the linear systems that arise. Two others use iterative (preconditioned Krylov) methods instead of direct methods for these linear systems. The most recent addition is LSODIS, which solves implicit problems with general sparse treatment of all matrices involved. The ODEPACK solvers are written in standard Fortran 77, with a few exceptions, and with minimal machine dependencies. There are separate double and single precision versions of ODEPACK. The actual solver names are those given above with a prefix of D- or S- for the double or single precision version, respectively, i.e. DLSODE/SLSODE, etc. Each solver consists of a main driver subroutine having the same name as the solver and some number of subordinate routines. For each solver, there is also a demonstration program, which solves one or two simple problems in a somewhat self-checking manner. A. Solvers for explicitly given systems. For each of the following solvers, it is assumed that the ODEs are given explicitly, so that the system can be written in the form dy/dt = f(t,y), where y is the vector of dependent variables, and t is the independent variable. 1. LSODE (Livermore Solver for Ordinary Differential Equations) is the basic solver of the collection. It solves stiff and non-stiff systems of the form dy/dt = f. In the stiff case, it treats the Jacobian matrix df/dy as either a dense (full) or a banded matrix, and as

Chondroitin Sulfate Is Indispensable for Pluripotency and Differentiation of Mouse Embryonic Stem Cells

Science.gov (United States)

Izumikawa, Tomomi; Sato, Ban; Kitagawa, Hiroshi

2014-01-01

Chondroitin sulfate (CS) proteoglycans are present on the surfaces of virtually all cells and in the extracellular matrix and are required for cytokinesis at early developmental stages. Studies have shown that heparan sulfate (HS) is essential for maintaining mouse embryonic stem cells (ESCs) that are primed for differentiation, whereas the function of CS has not yet been elucidated. To clarify the role of CS, we generated glucuronyltransferase-I-knockout ESCs lacking CS. We found that CS was required to maintain the pluripotency of ESCs and promoted initial ESC commitment to differentiation compared with HS. In addition, CS-A and CS-E polysaccharides, but not CS-C polysaccharides, bound to E-cadherin and enhanced ESC differentiation. Multiple-lineage differentiation was inhibited in chondroitinase ABC-digested wild-type ESCs. Collectively, these results suggest that CS is a novel determinant in controlling the functional integrity of ESCs via binding to E-cadherin.

Different requirements of functional telomeres in neural stem cells and terminally differentiated neurons.

Science.gov (United States)

Lobanova, Anastasia; She, Robert; Pieraut, Simon; Clapp, Charlie; Maximov, Anton; Denchi, Eros Lazzerini

2017-04-01

Telomeres have been studied extensively in peripheral tissues, but their relevance in the nervous system remains poorly understood. Here, we examine the roles of telomeres at distinct stages of murine brain development by using lineage-specific genetic ablation of TRF2, an essential component of the shelterin complex that protects chromosome ends from the DNA damage response machinery. We found that functional telomeres are required for embryonic and adult neurogenesis, but their uncapping has surprisingly no detectable consequences on terminally differentiated neurons. Conditional knockout of TRF2 in post-mitotic immature neurons had virtually no detectable effect on circuit assembly, neuronal gene expression, and the behavior of adult animals despite triggering massive end-to-end chromosome fusions across the brain. These results suggest that telomeres are dispensable in terminally differentiated neurons and provide mechanistic insight into cognitive abnormalities associated with aberrant telomere length in humans. © 2017 Lobanova et al.; Published by Cold Spring Harbor Laboratory Press.

Continuum and Discrete Initial-Boundary Value Problems and Einstein's Field Equations

Directory of Open Access Journals (Sweden)

Olivier Sarbach

2012-08-01

Full Text Available Many evolution problems in physics are described by partial differential equations on an infinite domain; therefore, one is interested in the solutions to such problems for a given initial dataset. A prominent example is the binary black-hole problem within Einstein's theory of gravitation, in which one computes the gravitational radiation emitted from the inspiral of the two black holes, merger and ringdown. Powerful mathematical tools can be used to establish qualitative statements about the solutions, such as their existence, uniqueness, continuous dependence on the initial data, or their asymptotic behavior over large time scales. However, one is often interested in computing the solution itself, and unless the partial differential equation is very simple, or the initial data possesses a high degree of symmetry, this computation requires approximation by numerical discretization. When solving such discrete problems on a machine, one is faced with a finite limit to computational resources, which leads to the replacement of the infinite continuum domain with a finite computer grid. This, in turn, leads to a discrete initial-boundary value problem. The hope is to recover, with high accuracy, the exact solution in the limit where the grid spacing converges to zero with the boundary being pushed to infinity. The goal of this article is to review some of the theory necessary to understand the continuum and discrete initial boundary-value problems arising from hyperbolic partial differential equations and to discuss its applications to numerical relativity; in particular, we present well-posed initial and initial-boundary value formulations of Einstein's equations, and we discuss multi-domain high-order finite difference and spectral methods to solve them.

Continuum and Discrete Initial-Boundary Value Problems and Einstein's Field Equations.

Science.gov (United States)

Sarbach, Olivier; Tiglio, Manuel

2012-01-01

Many evolution problems in physics are described by partial differential equations on an infinite domain; therefore, one is interested in the solutions to such problems for a given initial dataset. A prominent example is the binary black-hole problem within Einstein's theory of gravitation, in which one computes the gravitational radiation emitted from the inspiral of the two black holes, merger and ringdown. Powerful mathematical tools can be used to establish qualitative statements about the solutions, such as their existence, uniqueness, continuous dependence on the initial data, or their asymptotic behavior over large time scales. However, one is often interested in computing the solution itself, and unless the partial differential equation is very simple, or the initial data possesses a high degree of symmetry, this computation requires approximation by numerical discretization. When solving such discrete problems on a machine, one is faced with a finite limit to computational resources, which leads to the replacement of the infinite continuum domain with a finite computer grid. This, in turn, leads to a discrete initial-boundary value problem. The hope is to recover, with high accuracy, the exact solution in the limit where the grid spacing converges to zero with the boundary being pushed to infinity. The goal of this article is to review some of the theory necessary to understand the continuum and discrete initial boundary-value problems arising from hyperbolic partial differential equations and to discuss its applications to numerical relativity; in particular, we present well-posed initial and initial-boundary value formulations of Einstein's equations, and we discuss multi-domain high-order finite difference and spectral methods to solve them.

NFAT5 regulates the canonical Wnt pathway and is required for cardiomyogenic differentiation

International Nuclear Information System (INIS)

Adachi, Atsuo; Takahashi, Tomosaburo; Ogata, Takehiro; Imoto-Tsubakimoto, Hiroko; Nakanishi, Naohiko; Ueyama, Tomomi; Matsubara, Hiroaki

2012-01-01

Highlights: ► NFAT5 protein expression is downregulated during cardiomyogenesis. ► Inhibition of NFAT5 function suppresses canonical Wnt signaling. ► Inhibition of NFAT5 function attenuates mesodermal induction. ► NFAT5 function is required for cardiomyogenesis. -- Abstract: While nuclear factor of activated T cells 5 (NFAT5), a transcription factor implicated in osmotic stress response, is suggested to be involved in other processes such as migration and proliferation, its role in cardiomyogenesis is largely unknown. Here, we examined the role of NFAT5 in cardiac differentiation of P19CL6 cells, and observed that it was abundantly expressed in undifferentiated P19CL6 cells, and its protein expression was significantly downregulated by enhanced proteasomal degradation during DMSO-induced cardiomyogenesis. Expression of a dominant negative mutant of NFAT5 markedly attenuated cardiomyogenesis, which was associated with the inhibition of mesodermal differentiation. TOPflash reporter assay revealed that the transcriptional activity of canonical Wnt signaling was activated prior to mesodermal differentiation, and this activation was markedly attenuated by NFAT5 inhibition. Pharmacological activation of canonical Wnt signaling by [2′Z, 3′E]-6-bromoindirubin-3′-oxime (BIO) restored Brachyury expression in NFAT5DN-expressing cells. Inhibition of NFAT5 markedly attenuated Wnt3 and Wnt3a induction. Expression of Dkk1 and Cerberus1, which are secreted Wnt antagonists, was also inhibited by NFAT5 inhibition. Thus, endogenous NFAT5 regulates the coordinated expression of Wnt ligands and antagonists, which are essential for cardiomyogenesis through the canonical Wnt pathway. These results demonstrated a novel role of NFAT5 in cardiac differentiation of stem cells.

Reducing the memory requirement in reverse mode automatic differentiation by solving TBR flow equations

International Nuclear Information System (INIS)

Naumann, U.

2002-01-01

The fast computation of gradients in reverse mode Automatic Differentiation (AD) requires the generation of adjoint versions of every statement in the original code. Due to the resulting reversal of the control flow certain intermediate values have to be made available in reverse order to compute the local partial derivatives. This can be achieved by storing these values or by recomputing them when they become required. In any case one is interested in minimizing the size of this set. Following an extensive introduction of the ''To-Be-Recorded'' (TBR) problem the authors present flow equations for propagating the TBR status of variables in the context of reverse mode AD of structured programs

Differential Equation over Banach Algebra

OpenAIRE

Kleyn, Aleks

2018-01-01

In the book, I considered differential equations of order $1$ over Banach $D$-algebra: differential equation solved with respect to the derivative; exact differential equation; linear homogeneous equation. In noncommutative Banach algebra, initial value problem for linear homogeneous equation has infinitely many solutions.

Requirement of cAMP signaling for Schwann cell differentiation restricts the onset of myelination.

Directory of Open Access Journals (Sweden)

Ketty Bacallao

Full Text Available Isolated Schwann cells (SCs respond to cAMP elevation by adopting a differentiated post-mitotic state that exhibits high levels of Krox-20, a transcriptional enhancer of myelination, and mature SC markers such as the myelin lipid galactocerebroside (O1. To address how cAMP controls myelination, we performed a series of cell culture experiments which compared the differentiating responses of isolated and axon-related SCs to cAMP analogs and ascorbate, a known inducer of axon ensheathment, basal lamina formation and myelination. In axon-related SCs, cAMP induced the expression of Krox-20 and O1 without a concomitant increase in the expression of myelin basic protein (MBP and without promoting axon ensheathment, collagen synthesis or basal lamina assembly. When cAMP was provided together with ascorbate, a dramatic enhancement of MBP expression occurred, indicating that cAMP primes SCs to form myelin only under conditions supportive of basal lamina formation. Experiments using a combination of cell permeable cAMP analogs and type-selective adenylyl cyclase (AC agonists and antagonists revealed that selective transmembrane AC (tmAC activation with forskolin was not sufficient for full SC differentiation and that the attainment of an O1 positive state also relied on the activity of the soluble AC (sAC, a bicarbonate sensor that is insensitive to forskolin and GPCR activation. Pharmacological and immunological evidence indicated that SCs expressed sAC and that sAC activity was required for morphological differentiation and the expression of myelin markers such as O1 and protein zero. To conclude, our data indicates that cAMP did not directly drive myelination but rather the transition into an O1 positive state, which is perhaps the most critical cAMP-dependent rate limiting step for the onset of myelination. The temporally restricted role of cAMP in inducing differentiation independently of basal lamina formation provides a clear example of the

[Desmoplastic fibroma. Differential diagnosis of a periapical lesion from endodontic failure].

Science.gov (United States)

Zabalegui, B; Gil, J; Zabalegui, I

1989-01-01

Treatment of endodontically involved teeth requires accurate diagnosis of the clinical pulpal condition to determine the primary cause of pathosis. The case presented shows the differential diagnosis between a desmoplastic fibroma and a failure of a misdiagnosed endodontic treatment. The initial direction of treatment should had never been the endodontic therapy but local surgical curettage of the lesion.

Power system requirements and selection for the space exploration initiative

International Nuclear Information System (INIS)

Biringer, K.L.; Bartine, D.E.; Buden, D.; Foreman, J.; Harrison, S.

1991-01-01

The Space Exploration Initiative (SEI) seeks to reestablish a US program of manned and unmanned space exploration. The President has called for a program which includes a space station element, a manned habitation of the moon, and a human exploration of Mars. The NASA Synthesis Group has developed four significantly different architectures for the SEI program. One key element of a space exploration effort is the power required to support the missions. The Power Speciality Team of the Synthesis Group was tasked with assessing and evaluating the power requirements and candidate power technologies for such missions. Inputs to the effort came from existing NASA studies as well as other governments agency inputs such as those from DOD and DOE. In addition, there were industry and university briefings and results of solicitations from the AIAA and the general public as part of the NASA outreach effort. Because of the variety of power needs in the SEI program, there will be a need for multiple power system technologies including solar, nuclear and electrochemical. Due to the high rocket masses required to propel payloads to the moon and beyond to Mars, there is great emphasis placed on the need for high power density and high energy density systems. Power system technology development work is needed results will determine the ultimate technology selections. 23 refs., 10 figs

Brief Report: High and Low Level Initiations of Joint Attention, and Response to Joint Attention--Differential Relationships with Language and Imitation

Science.gov (United States)

Pickard, Katherine E.; Ingersoll, Brooke R.

2015-01-01

Frequency of high-level (showing/pointing) and low-level (coordinated gaze shifts) behaviors on the Early Social Communication Scales are often used as a measure of joint attention initiations (IJA). This study examined the degree to which these skills and response to joint attention (RJA; e.g. gaze following) were differentially related to…

Differential geometry connections, curvature, and characteristic classes

CERN Document Server

Tu, Loring W

2017-01-01

This text presents a graduate-level introduction to differential geometry for mathematics and physics students. The exposition follows the historical development of the concepts of connection and curvature with the goal of explaining the Chern–Weil theory of characteristic classes on a principal bundle. Along the way we encounter some of the high points in the history of differential geometry, for example, Gauss' Theorema Egregium and the Gauss–Bonnet theorem. Exercises throughout the book test the reader’s understanding of the material and sometimes illustrate extensions of the theory. Initially, the prerequisites for the reader include a passing familiarity with manifolds. After the first chapter, it becomes necessary to understand and manipulate differential forms. A knowledge of de Rham cohomology is required for the last third of the text. Prerequisite material is contained in author's text An Introduction to Manifolds, and can be learned in one semester. For the benefit of the reader and to establ...

TGF-β receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

International Nuclear Information System (INIS)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian; Brandan, Enrique

2010-01-01

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type β (TGF-β), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-β-receptors (TGF-β-Rs) during skeletal muscle differentiation. We found a decrease of TGF-β signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-β. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-β-R type I (TGF-β-RI) and type II (TGF-β-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-β-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-β-RII lacking the cytoplasmic domain. The TGF-β-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-β-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-β receptors independent of Smad proteins are essential for skeletal muscle differentiation.

TGF-{beta} receptors, in a Smad-independent manner, are required for terminal skeletal muscle differentiation

Energy Technology Data Exchange (ETDEWEB)

Droguett, Rebeca; Cabello-Verrugio, Claudio; Santander, Cristian [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile); Brandan, Enrique, E-mail: ebrandan@bio.puc.cl [Centro de Regulacion Celular y Patologia, Centro de Regeneracion y Envejecimiento (CARE), Departamento de Biologia Celular y Molecular, MIFAB, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2010-09-10

Skeletal muscle differentiation is strongly inhibited by transforming growth factor type {beta} (TGF-{beta}), although muscle formation as well as regeneration normally occurs in an environment rich in this growth factor. In this study, we evaluated the role of intracellular regulatory Smads proteins as well as TGF-{beta}-receptors (TGF-{beta}-Rs) during skeletal muscle differentiation. We found a decrease of TGF-{beta} signaling during differentiation. This phenomenon is explained by a decline in the levels of the regulatory proteins Smad-2, -3, and -4, a decrease in the phosphorylation of Smad-2 and lost of nuclear translocation of Smad-3 and -4 in response to TGF-{beta}. No change in the levels and inhibitory function of Smad-7 was observed. In contrast, we found that TGF-{beta}-R type I (TGF-{beta}-RI) and type II (TGF-{beta}-RII) increased on the cell surface during skeletal muscle differentiation. To analyze the direct role of the serine/threonine kinase activities of TGF-{beta}-Rs, we used the specific inhibitor SB 431542 and the dominant-negative form of TGF-{beta}-RII lacking the cytoplasmic domain. The TGF-{beta}-Rs were important for successful muscle formation, determined by the induction of myogenin, creatine kinase activity, and myosin. Silencing of Smad-2/3 expression by specific siRNA treatments accelerated myogenin, myosin expression, and myotube formation; although when SB 431542 was present inhibition in myosin induction and myotube formation was observed, suggesting that these last steps of skeletal muscle differentiation require active TGF-{beta}-Rs. These results suggest that both down-regulation of Smad regulatory proteins and cell signaling through the TGF-{beta} receptors independent of Smad proteins are essential for skeletal muscle differentiation.

Differential requirements for Gli2 and Gli3 in the regional specification of the mouse hypothalamus

Directory of Open Access Journals (Sweden)

Roberta eHaddad-Tóvolli

2015-03-01

Full Text Available Secreted protein Sonic hedgehog (Shh ventralizes the neural tube by modulating the crucial balance between activating and repressing functions (GliA, GliR of transcription factors Gli2 and Gli3. This balance—the Shh-Gli code—is species- and context-dependent and has been elucidated for the mouse spinal cord. The hypothalamus, a forebrain region regulating vital functions like homeostasis and hormone secretion, shows dynamic and intricate Shh expression as well as complex regional differentiation. Here we asked if particular combinations of Gli2 and Gli3 and of GliA and GliR functions contribute to the variety of hypothalamic regions, i.e. we wanted to clarify the hypothalamic version of the Shh-Gli code. Based on mouse mutant analysis, we show that: 1 hypothalamic regional heterogeneity is based in part on differentially stringent requirements for Gli2 or Gli3; 2 another source of diversity are differential requirements for Shh of neural vs non-neural origin; 3 Gli2 is indispensable for the specification of a medial progenitor domain generating several essential hypothalamic nuclei plus the pituitary and median eminence; 4 the suppression of Gli3R by neural and non-neural Shh is essential for hypothalamic specification. Finally, we have mapped our results on a recent model which considers the hypothalamus as a transverse region with alar and basal portions. Our data confirm the model and are explained by it.

Justification of response time testing requirements for pressure and differential pressure sensors

International Nuclear Information System (INIS)

Weiss, J.M.; Mayo, C.; Swisher, V.

1991-01-01

This paper reports on response time testing (RTT) requirements that were imposed on pressure, differential pressure sensors as a conservative approach to insure that assumptions in the plant safety analyses were met. The purpose of this project has been to identify the need for response time testing using the bases identified in IEEE Standard 338. A combination of plant data analyses, failure modes, and effects analyses (FMEAs) was performed. Eighteen currently qualified sensor models were utilized. The results of these analyses indicate that there are only two failure modes that affect response time, not sensor output concurrently. For these failure modes, appropriate plant actions and testing techniques were identified. Safety system RTT requirements were established by IEEE Standard 338-1975. Criteria for the Periodic Testing of Class IE Power, Protection Systems, presuming the need existed for this testing. This standard established guidelines for periodic testing to verify that loop response times of installed nuclear safety-related equipment were within the limits presumed by the design basis plant transient, accident analyses. The requirements covered all passive, active components in an instrument loop, including sensors. Individual components could be tested either in groups or separately to determine the overall loop response time

40 CFR 63.7826 - How do I demonstrate initial compliance with the operation and maintenance requirements that...

Science.gov (United States)

2010-07-01

... preventative maintenance schedule and, as applicable, detailed descriptions of the corrective action procedures... compliance with the operation and maintenance requirements that apply to me? 63.7826 Section 63.7826... Compliance Requirements § 63.7826 How do I demonstrate initial compliance with the operation and maintenance...

Experience in initial training required for the recognition of the qualified RP expert in Spain

International Nuclear Information System (INIS)

Rodriguez Suarez, M.; Marco Arboli, M.; Menarguez, J.

2003-01-01

An important point of the actions inside the European framework to achieve the harmonisation of the training programmes and recognition was included in the European directive 96/29/Euratom which includes definition and specific tasks of the European Qualified Expert on Radiation Protection (RP). Basic syllabus for training of those experts was developed in the communication 98/C 133/03 concerning BSS applications. Although, in the Spanish education system, the training and recognition requirements of the high level qualified experts on RP was defined since 1977, until 2001, the figure of the Technical Qualified Expert on RP does not appear in the legal framework. In December 2002, a new regulation of the Spanish Regulatory Body, CSN, about qualifications to obtain the recognition of RP Expert in Spain (both high qualified and technical RP experts) was published. Concerning the qualified expert on RP, (RP Officer), responsible of the RP Service, which takes charge of the effective protection and advise radioactive and nuclear facilities in Rp aspects,has to be authorised by the regulatory body. to obtain the RP officer diploma, conceded by the CSN, an initial training of 300 hours and a three-year minimum experience are required (for X-ray installation a 6-month experience is enough). The technical qualified expert on RP is the worker who carried out the tasks in the a RP Service under the supervision of the RP officer. A Technician Qualified Expert on RP does not need an specific accreditation of the Regulatory Body, but an initial RP training and a three-month minimum experience are required and has hold a certificate by the RP officer. Continuous training is also required and as well has to receive a certificate from the RP officer. Since 1977, The Institute for energy Studies has been implementing specific training courses for those professionals who want to obtain the diploma of RP officer (high degree qualified RP expert), conceded by the CSN. Since then

Functions and requirements for Project W-236B, Initial Pretreatment Module: Revision 1

International Nuclear Information System (INIS)

Swanson, L.M.

1994-01-01

Hanford Site tank waste supernatants will be pretreated to separate the low-level and high-level fractions. The low-level waste fraction, containing the bulk of the chemical constituents, must be processed into a vitrified waste product which will be disposed of onsite, in a safe, environmentally sound, and cost effective manner. The high-level waste fraction separated during supernatant pretreatment (primarily cesium) will be recombined with an additional high-level waste fraction generated from pretreatment of the tank waste sludges and solids. This combined high-level waste fraction will be immobilized as glass and disposed in a geological repository. The purpose of this document is to establish the functional requirements baseline for Project W-236B, Initial Pretreatment Module, by defining the level 5 and 6 functions and requirements for the project. A functional analysis approach has been used to break down the program functions and associated physical requirements that each function must meet. As the systems engineering process evolves, the design requirements document will replace this preliminary functions and requirements document. The design requirements document (DRD) will identify key decisions and associated uncertainties that impact the project. A revision of this document to a DRD is not expected to change the performance requirements or open issues. However, additional requirements and issues may be identified

Errorless discrimination established by differential autoshaping.

Science.gov (United States)

Wilkie, D M; Ramer, D G

1974-09-01

In Experiment I, pigeons exposed to a differential autoshaping procedure pecked a key in the presence of the stimulus associated with reinforcement but did not peck, or pecked infrequently, in the presence of the stimulus associated with nonreinforcement. In Experiment II, pigeons were exposed to a differential autoshaping procedure in which one stimulus was associated with reinforcement and two stimuli were associated with nonreinforcement. The birds initially responded in the presence of one stimulus associated with nonreinforcement but never responded in the presence of the second stimulus associated with nonreinforcement. They were subsequently exposed to an autoshaping procedure in which reinforcement followed both these stimuli. The number of stimulus-reinforcement pairings required to establish pecking in the presence of the stimulus during which responses had not previously occurred suggested that such stimuli are inhibitory. These findings have implications for autoshaping, errorless discrimination, inhibition, and theories of discrimination byproducts.

EXTRA: a digital computer program for the solution of stiff sets of ordinary initial value, first order differential equations

International Nuclear Information System (INIS)

Sidell, J.

1976-08-01

EXTRA is a program written for the Winfrith KDF9 enabling the user to solve first order initial value differential equations. In this report general numerical integration methods are discussed with emphasis on their application to the solution of stiff sets of equations. A method of particular applicability to stiff sets of equations is described. This method is incorporated in the program EXTRA and full instructions for its use are given. A comparison with other methods of computation is included. (author)

Yap1 is dispensable for self-renewal but required for proper differentiation of mouse embryonic stem (ES) cells.

Science.gov (United States)

Chung, HaeWon; Lee, Bum-Kyu; Uprety, Nadima; Shen, Wenwen; Lee, Jiwoon; Kim, Jonghwan

2016-04-01

Yap1 is a transcriptional co-activator of the Hippo pathway. The importance of Yap1 in early cell fate decision during embryogenesis has been well established, though its role in embryonic stem (ES) cells remains elusive. Here, we report that Yap1 plays crucial roles in normal differentiation rather than self-renewal of ES cells. Yap1-depleted ES cells maintain undifferentiated state with a typical colony morphology as well as robust alkaline phosphatase activity. These cells also retain comparable levels of the core pluripotent factors, such as Pou5f1 and Sox2, to the levels in wild-type ES cells without significant alteration of lineage-specific marker genes. Conversely, overexpression of Yap1 in ES cells promotes nuclear translocation of Yap1, resulting in disruption of self-renewal and triggering differentiation by up-regulating lineage-specific genes. Moreover, Yap1-deficient ES cells show impaired induction of lineage markers during differentiation. Collectively, our data demonstrate that Yap1 is a required factor for proper differentiation of mouse ES cells, while remaining dispensable for self-renewal. © 2016 The Authors.

A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells.

Directory of Open Access Journals (Sweden)

Tetsuo Yasugi

Full Text Available Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da protein and its mammalian counterparts (E12/E47 act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.

Core Problem: Does the CV Parent Body Magnetization require differentiation?

Science.gov (United States)

O'Brien, T.; Tarduno, J. A.; Smirnov, A. V.

2016-12-01

Evidence for the presence of past dynamos from magnetic studies of meteorites can provide key information on the nature and evolution of parent bodies. However, the suggestion of a past core dynamo for the CV parent body based on the study of the Allende meteorite has led to a paradox: a core dynamo requires differentiation, evidence for which is missing in the meteorite record. The key parameter used to distinguish core dynamo versus external field mechanisms is absolute field paleointensity, with high values (>>1 μT) favoring the former. Here we explore the fundamental requirements for absolute field intensity measurement in the Allende meteorite: single domain grains that are non-interacting. Magnetic hysteresis and directional data define strong magnetic interactions, negating a standard interpretation of paleointensity measurements in terms of absolute paleofield values. The Allende low field magnetic susceptibility is dominated by magnetite and FeNi grains, whereas the magnetic remanence is carried by an iron sulfide whose remanence-carrying capacity increases with laboratory cycling at constant field values, indicating reordering. The iron sulfide and FeNi grains are in close proximity, providing mineralogical context for interactions. We interpret the magnetization of Allende to record the intense early solar wind with metal-sulfide interactions amplifying the field, giving the false impression of a higher field value in some prior studies. An undifferentiated CV parent body is thus compatible with Allende's magnetization. Early solar wind magnetization should be the null hypothesis for evaluating the source of magnetization for chondrites and other meteorites.

The requirement for pre-TCR during thymic differentiation enforces a developmental pause that is essential for V-DJβ rearrangement.

Directory of Open Access Journals (Sweden)

Karen S Hathcock

Full Text Available T cell development occurs in the thymus and is critically dependent on productive TCRβ rearrangement and pre-TCR expression in DN3 cells. The requirement for pre-TCR expression results in the arrest of thymocytes at the DN3 stage (β checkpoint, which is uniquely permissive for V-DJβ recombination; only cells expressing pre-TCR survive and develop beyond the DN3 stage. In addition, the requirement for TCRβ rearrangement and pre-TCR expression enforces suppression of TCRβ rearrangement on a second allele, allelic exclusion, thus ensuring that each T cell expresses only a single TCRβ product. However, it is not known whether pre-TCR expression is essential for allelic exclusion or alternatively if allelic exclusion is enforced by developmental changes that can occur in the absence of pre-TCR. We asked if thymocytes that were differentiated without pre-TCR expression, and therefore without pause at the β checkpoint, would suppress all V-DJβ rearrangement. We previously reported that premature CD28 signaling in murine CD4(-CD8(- (DN thymocytes supports differentiation of CD4(+CD8(+ (DP cells in the absence of pre-TCR expression. The present study uses this model to define requirements for TCRβ rearrangement and allelic exclusion. We demonstrate that if cells exit the DN3 developmental stage before TCRβ rearrangement occurs, V-DJβ rearrangement never occurs, even in DP cells that are permissive for D-Jβ and TCRα rearrangement. These results demonstrate that pre-TCR expression is not essential for thymic differentiation to DP cells or for V-DJβ suppression. However, the requirement for pre-TCR signals and the exclusion of alternative stimuli such as CD28 enforce a developmental "pause" in early DN3 cells that is essential for productive TCRβ rearrangement to occur.

Leukotriene synthesis is required for hedgehog-dependent neurite projection in neuralized embryoid bodies but not for motor neuron differentiation

NARCIS (Netherlands)

Bijlsma, Maarten F.; Peppelenbosch, Maikel P.; Spek, C. Arnold; Roelink, Henk

The hedgehog (Hh) pathway is required for many developmental processes,. as well as for adult homeostasis. Although all known effects of Hh signaling affecting patterning and differentiation are mediated by members of the Gli family of zinc ringer transcription factors, we demonstrate that the

A Numerical Method for Partial Differential Algebraic Equations Based on Differential Transform Method

Directory of Open Access Journals (Sweden)

Murat Osmanoglu

2013-01-01

Full Text Available We have considered linear partial differential algebraic equations (LPDAEs of the form , which has at least one singular matrix of . We have first introduced a uniform differential time index and a differential space index. The initial conditions and boundary conditions of the given system cannot be prescribed for all components of the solution vector here. To overcome this, we introduced these indexes. Furthermore, differential transform method has been given to solve LPDAEs. We have applied this method to a test problem, and numerical solution of the problem has been compared with analytical solution.

Voltage-gated sodium channel expression and action potential generation in differentiated NG108-15 cells.

Science.gov (United States)

Liu, Jinxu; Tu, Huiyin; Zhang, Dongze; Zheng, Hong; Li, Yu-Long

2012-10-25

The generation of action potential is required for stimulus-evoked neurotransmitter release in most neurons. Although various voltage-gated ion channels are involved in action potential production, the initiation of the action potential is mainly mediated by voltage-gated Na+ channels. In the present study, differentiation-induced changes of mRNA and protein expression of Na+ channels, Na+ currents, and cell membrane excitability were investigated in NG108-15 cells. Whole-cell patch-clamp results showed that differentiation (9 days) didn't change cell membrane excitability, compared to undifferentiated state. But differentiation (21 days) induced the action potential generation in 45.5% of NG108-15 cells (25/55 cells). In 9-day-differentiated cells, Na+ currents were mildly increased, which was also found in 21-day differentiated cells without action potential. In 21-day differentiated cells with action potential, Na+ currents were significantly enhanced. Western blot data showed that the expression of Na+ channels was increased with differentiated-time dependent manner. Single-cell real-time PCR data demonstrated that the expression of Na+ channel mRNA was increased by 21 days of differentiation in NG108-15 cells. More importantly, the mRNA level of Na+ channels in cells with action potential was higher than that in cells without action potential. Differentiation induces expression of voltage-gated Na+ channels and action potential generation in NG108-15 cells. A high level of the Na+ channel density is required for differentiation-triggered action potential generation.

Differentiation of subdural effusions

International Nuclear Information System (INIS)

Wetterling, T.; Rama, B.

1989-01-01

Although X-ray computerized tomography facilitates the diagnosis of intracranial disorders, differentiation of the lesions like extracerebral effusions is often unsatisfactory. Epidural and acute subdural haematoma shown as hyperdensity in CT requires an emergency neurosurgical operation, so that differentiation of these hyperdense effusions may not be required. But the discrimination of the effusions shown as hypodensity in CT (chronic subdural haematoma, subdural hygroma, subdural empyema as well as arachnoid cysts) is urgent because of the different treatment of these effusions. The clinical differentiation is hampered by unspecific neurologic symptoms and the lack of adequate laboratory tests. Some aspects facilitating the diagnostic decision are presented. Recent magnetic resonance (MR) studies promise further progress in differentiating between subdural effusions. (orig.) [de

Errorless discrimination established by differential autoshaping1

Science.gov (United States)

Wilkie, Donald M.; Ramer, Donald G.

1974-01-01

In Experiment I, pigeons exposed to a differential autoshaping procedure pecked a key in the presence of the stimulus associated with reinforcement but did not peck, or pecked infrequently, in the presence of the stimulus associated with nonreinforcement. In Experiment II, pigeons were exposed to a differential autoshaping procedure in which one stimulus was associated with reinforcement and two stimuli were associated with nonreinforcement. The birds initially responded in the presence of one stimulus associated with nonreinforcement but never responded in the presence of the second stimulus associated with nonreinforcement. They were subsequently exposed to an autoshaping procedure in which reinforcement followed both these stimuli. The number of stimulus-reinforcement pairings required to establish pecking in the presence of the stimulus during which responses had not previously occurred suggested that such stimuli are inhibitory. These findings have implications for autoshaping, errorless discrimination, inhibition, and theories of discrimination byproducts. PMID:16811797

Differentiated taxation - a requirement of fiscal equity

OpenAIRE

Ionut-Catalin CROITORU; Coralia Emilia POPA

2012-01-01

Fiscal policy is a central concern of each State and one of the direct ways to influence economic and social development by using taxes. This paper aims to make an analysis on the two currently used methods of taxation: differentiated progressive taxation, according to the size of income, and the proportional taxation by using a single tax rate. The basic idea of this paper is that progressive taxation can reduce inequality and increase social benefits. There are also considered the tax syste...

CANONICAL BACKWARD DIFFERENTIATION SCHEMES FOR ...

African Journals Online (AJOL)

This paper describes a new nonlinear backward differentiation schemes for the numerical solution of nonlinear initial value problems of first order ordinary differential equations. The schemes are based on rational interpolation obtained from canonical polynomials. They are A-stable. The test problems show that they give ...

Direct Measurement of Initial Enrichment, Burn-up and Cooling Time of Spent Fuel Assembly with a Differential Die-Away Technique Based Instrument

International Nuclear Information System (INIS)

Henzl, Vladimir; Swinhoe, Martyn T.; Tobin, Stephen J.

2012-01-01

An outline of this presentation of what a Differential Die-Away (DDA) instrument can do are: (1) Principle of operation of DDA instrument; (2) Determination of initial enrichment (IE) (σ DDA response increases (die-away time is longer) with increasing fissile content; and (2) Spent fuel => DDA response decreases (die-away time is shorter) with higher burn-up (i.e. more neutron absorbers present).

Optimal Error Estimates of Two Mixed Finite Element Methods for Parabolic Integro-Differential Equations with Nonsmooth Initial Data

KAUST Repository

Goswami, Deepjyoti

2013-05-01

In the first part of this article, a new mixed method is proposed and analyzed for parabolic integro-differential equations (PIDE) with nonsmooth initial data. Compared to the standard mixed method for PIDE, the present method does not bank on a reformulation using a resolvent operator. Based on energy arguments combined with a repeated use of an integral operator and without using parabolic type duality technique, optimal L2 L2-error estimates are derived for semidiscrete approximations, when the initial condition is in L2 L2. Due to the presence of the integral term, it is, further, observed that a negative norm estimate plays a crucial role in our error analysis. Moreover, the proposed analysis follows the spirit of the proof techniques used in deriving optimal error estimates for finite element approximations to PIDE with smooth data and therefore, it unifies both the theories, i.e., one for smooth data and other for nonsmooth data. Finally, we extend the proposed analysis to the standard mixed method for PIDE with rough initial data and provide an optimal error estimate in L2, L 2, which improves upon the results available in the literature. © 2013 Springer Science+Business Media New York.

SPDEF is required for mouse pulmonary goblet cell differentiation and regulates a network of genes associated with mucus production.

Science.gov (United States)

Chen, Gang; Korfhagen, Thomas R; Xu, Yan; Kitzmiller, Joseph; Wert, Susan E; Maeda, Yutaka; Gregorieff, Alexander; Clevers, Hans; Whitsett, Jeffrey A

2009-10-01

Various acute and chronic inflammatory stimuli increase the number and activity of pulmonary mucus-producing goblet cells, and goblet cell hyperplasia and excess mucus production are central to the pathogenesis of chronic pulmonary diseases. However, little is known about the transcriptional programs that regulate goblet cell differentiation. Here, we show that SAM-pointed domain-containing Ets-like factor (SPDEF) controls a transcriptional program critical for pulmonary goblet cell differentiation in mice. Initial cell-lineage-tracing analysis identified nonciliated secretory epithelial cells, known as Clara cells, as the progenitors of goblet cells induced by pulmonary allergen exposure in vivo. Furthermore, in vivo expression of SPDEF in Clara cells caused rapid and reversible goblet cell differentiation in the absence of cell proliferation. This was associated with enhanced expression of genes regulating goblet cell differentiation and protein glycosylation, including forkhead box A3 (Foxa3), anterior gradient 2 (Agr2), and glucosaminyl (N-acetyl) transferase 3, mucin type (Gcnt3). Consistent with these findings, levels of SPDEF and FOXA3 were increased in mouse goblet cells after sensitization with pulmonary allergen, and the proteins were colocalized in goblet cells lining the airways of patients with chronic lung diseases. Deletion of the mouse Spdef gene resulted in the absence of goblet cells in tracheal/laryngeal submucosal glands and in the conducting airway epithelium after pulmonary allergen exposure in vivo. These data show that SPDEF plays a critical role in regulating a transcriptional network mediating the goblet cell differentiation and mucus hyperproduction associated with chronic pulmonary disorders.

Differentiation of endosperm transfer cells of barley: a comprehensive analysis at the micro-scale.

Science.gov (United States)

Thiel, Johannes; Riewe, David; Rutten, Twan; Melzer, Michael; Friedel, Swetlana; Bollenbeck, Felix; Weschke, Winfriede; Weber, Hans

2012-08-01

Barley endosperm cells differentiate into transfer cells (ETCs) opposite the nucellar projection. To comprehensively analyse ETC differentiation, laser microdissection-based transcript and metabolite profiles were obtained from laser microdissected tissues and cell morphology was analysed. Flange-like secondary-wall ingrowths appeared between 5 and 7 days after pollination within the three outermost cell layers. Gene expression analysis indicated that ethylene-signalling pathways initiate ETC morphology. This is accompanied by gene activity related to cell shape control and vesicle transport, with abundant mitochondria and endomembrane structures. Gene expression analyses indicate predominant formation of hemicelluloses, glucuronoxylans and arabinoxylans, and transient formation of callose, together with proline and 4-hydroxyproline biosynthesis. Activation of the methylation cycle is probably required for biosynthesis of phospholipids, pectins and ethylene. Membrane microdomains involving sterols/sphingolipids and remorins are potentially involved in ETC development. The transcriptional activity of assimilate and micronutrient transporters suggests ETCs as the main uptake organs of solutes into the endosperm. Accordingly, the endosperm grows maximally after ETCs are fully developed. Up-regulated gene expression related to amino acid catabolism, C:N balances, carbohydrate oxidation, mitochondrial activity and starch degradation meets high demands for respiratory energy and carbohydrates, required for cell proliferation and wall synthesis. At 10 days after pollination, ETCs undergo further differentiation, potentially initiated by abscisic acid, and metabolism is reprogrammed as shown by activated storage and stress-related processes. Overall, the data provide a comprehensive view of barley ETC differentiation and development, and identify candidate genes and associated pathways. © 2012 The Authors. The Plant Journal © 2012 Blackwell Publishing Ltd.

Initial value formulation of dynamical Chern-Simons gravity

Science.gov (United States)

Delsate, Térence; Hilditch, David; Witek, Helvi

2015-01-01

We derive an initial value formulation for dynamical Chern-Simons gravity, a modification of general relativity involving parity-violating higher derivative terms. We investigate the structure of the resulting system of partial differential equations thinking about linearization around arbitrary backgrounds. This type of consideration is necessary if we are to establish well-posedness of the Cauchy problem. Treating the field equations as an effective field theory we find that weak necessary conditions for hyperbolicity are satisfied. For the full field equations we find that there are states from which subsequent evolution is not determined. Generically the evolution system closes, but is not hyperbolic in any sense that requires a first order pseudodifferential reduction. In a cursory mode analysis we find that the equations of motion contain terms that may cause ill-posedness of the initial value problem.

Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

DEFF Research Database (Denmark)

Hallenborg, Philip; Feddersen, Søren; Francoz, S.

2012-01-01

The role of the E3 ubiquitin ligase murine double minute 2 (Mdm2) in regulating the stability of the p53 tumor suppressor is well documented. By contrast, relatively little is known about p53-independent activities of Mdm2 and the role of Mdm2 in cellular differentiation. Here we report a novel r...... in the myoblast cell line C2C12, it is conceivable that Mdm2 acts as a switch in cell fate determination. Cell Death and Differentiation (2012) 19, 1381-1389; doi:10.1038/cdd.2012.15; published online 2 March 2012...

Improved Survival and Initiation of Differentiation of Human Induced Pluripotent Stem Cells to Hepatocyte-Like Cells upon Culture in William's E Medium followed by Hepatocyte Differentiation Inducer Treatment.

Directory of Open Access Journals (Sweden)

Minoru Tomizawa

Full Text Available Hepatocyte differentiation inducer (HDI lacks both glucose and arginine, but is supplemented with galactose and ornithine, and is added together with other reagents such as apoptosis inhibitor and oncostatin M. Although human induced pluripotent stem (iPS cells initiate hepatocyte differentiation, most die within 7 days. In this study, we investigated both HDI and conventional media for their potential to improve cell survival.201B7 iPS cells were cultured in conventional media. This consisted of three cycles of 5-day culture in William's E (WE medium, followed by a 2-day culture in HDI.Expression levels of α-feto protein (AFP were higher in cells cultured in WE and in Dulbecco's Modified Eagle's Medium/Nutrient F-12 Ham (DF12. 201B7 cells expressed the highest AFP and albumin (ALB when cultured in HDI for 2 days following 7-day culture in WE. After three cycles of 5-day culture in WE followed by 2 days in HDI, 201B7 cells expressed AFP and ALB 54 ± 2.3 (average ± standard deviation and 73 ± 15.1 times higher, respectively, than those cultured in ReproFF (feeder-free condition.201B7 cells survived culture in WE for 7 days followed HDI for 2 days. After three cycles of culture under these conditions, hepatocyte differentiation was enhanced, as evidenced by increased AFP and ALB expression.

Differentiation of the lateral compartment of the cochlea requires a temporally restricted FGF20 signal.

Directory of Open Access Journals (Sweden)

Sung-Ho Huh

2012-01-01

Full Text Available A large proportion of age-related hearing loss is caused by loss or damage to outer hair cells in the organ of Corti. The organ of Corti is the mechanosensory transducing apparatus in the inner ear and is composed of inner hair cells, outer hair cells, and highly specialized supporting cells. The mechanisms that regulate differentiation of inner and outer hair cells are not known. Here we report that fibroblast growth factor 20 (FGF20 is required for differentiation of cells in the lateral cochlear compartment (outer hair and supporting cells within the organ of Corti during a specific developmental time. In the absence of FGF20, mice are deaf and lateral compartment cells remain undifferentiated, postmitotic, and unresponsive to Notch-dependent lateral inhibition. These studies identify developmentally distinct medial (inner hair and supporting cells and lateral compartments in the developing organ of Corti. The viability and hearing loss in Fgf20 knockout mice suggest that FGF20 may also be a deafness-associated gene in humans.

Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity

DEFF Research Database (Denmark)

Hallenborg, Philip; Jørgensen, Claus; Petersen, Rasmus K

2010-01-01

preadipocytes. Here, we show that forced expression of eLOX3 or addition of eLOX3 products stimulated adipogenesis under conditions that normally require an exogenous PPAR gamma ligand for differentiation. Hepoxilins, a group of oxidized arachidonic acid derivatives produced by eLOX3, bound to and activated...... PPAR gamma. Production of hepoxilins was increased transiently during the initial stages of adipogenesis. Furthermore, small interfering RNA-mediated or retroviral short hairpin RNA-mediated knockdown of eLOX3 expression abolished differentiation of 3T3-L1 preadipocytes. Finally, we demonstrate...... differentiation has remained enigmatic. Previously, we showed that lipoxygenase (LOX) activity is involved in activation of PPAR gamma during the early stages of adipocyte differentiation. Of the seven known murine LOXs, only the unconventional LOX epidermis-type lipoxygenase 3 (eLOX3) is expressed in 3T3-L1...

A cross-talk between TrkB and Ret tyrosine kinases receptors mediates neuroblastoma cells differentiation.

Directory of Open Access Journals (Sweden)

Carla Lucia Esposito

Full Text Available Understanding the interplay between intracellular signals initiated by multiple receptor tyrosine kinases (RTKs to give the final cell phenotype is a major pharmacological challenge. Retinoic acid (RA-treatment of neuroblastoma (NB cells implicates activation of Ret and TrkB RTKs as critical step to induce cell differentiation. By studying the signaling interplay between TrkB and Ret as paradigmatic example, here we demonstrate the existence of a cross-talk mechanism between the two unrelated receptors that is needed to induce the cell differentiation. Indeed, we show that TrkB receptor promotes Ret phosphorylation by a mechanism that does not require GDNF. This reveals to be a key mechanism, since blocking either TrkB or Ret by small interfering RNA causes a failure in NB biochemical and morphological differentiation. Our results provide the first evidence that a functional transactivation between distinct tyrosine kinases receptors is required for an important physiological process.

Physical interactions between bacteriophage and Escherichia coli proteins required for initiation of lambda DNA replication.

Science.gov (United States)

Liberek, K; Osipiuk, J; Zylicz, M; Ang, D; Skorko, J; Georgopoulos, C

1990-02-25

The process of initiation of lambda DNA replication requires the assembly of the proper nucleoprotein complex at the origin of replication, ori lambda. The complex is composed of both phage and host-coded proteins. The lambda O initiator protein binds specifically to ori lambda. The lambda P initiator protein binds to both lambda O and the host-coded dnaB helicase, giving rise to an ori lambda DNA.lambda O.lambda P.dnaB structure. The dnaK and dnaJ heat shock proteins have been shown capable of dissociating this complex. The thus freed dnaB helicase unwinds the duplex DNA template at the replication fork. In this report, through cross-linking, size chromatography, and protein affinity chromatography, we document some of the protein-protein interactions occurring at ori lambda. Our results show that the dnaK protein specifically interacts with both lambda O and lambda P, and that the dnaJ protein specifically interacts with the dnaB helicase.

Lamin A/C Is Required for ChAT-Dependent Neuroblastoma Differentiation.

Science.gov (United States)

Guglielmi, Loredana; Nardella, Marta; Musa, Carla; Iannetti, Ilaria; Arisi, Ivan; D'Onofrio, Mara; Storti, Andrea; Valentini, Alessandra; Cacci, Emanuele; Biagioni, Stefano; Augusti-Tocco, Gabriella; D'Agnano, Igea; Felsani, Armando

2017-07-01

The mouse neuroblastoma N18TG2 clone is unable to differentiate and is defective for the enzymes of the biosynthesis of neurotransmitters. The forced expression of choline acetyltransferase (ChAT) in these cells results in the synthesis and release of acetylcholine (Ach) and hence in the expression of neurospecific features and markers. To understand how the expression of ChAT triggered neuronal differentiation, we studied the differences in genome-wide transcription profiles between the N18TG2 parental cells and its ChAT-expressing 2/4 derived clone. The engagement of the 2/4 cells in the neuronal developmental program was confirmed by the increase of the expression level of several differentiation-related genes and by the reduction of the amount of transcripts of cell cycle genes. At the same time, we observed a massive reorganization of cytoskeletal proteins in terms of gene expression, with the accumulation of the nucleoskeletal lamina component Lamin A/C in differentiating cells. The increase of the Lmna transcripts induced by ChAT expression in 2/4 cells was mimicked treating the parental N18TG2 cells with the acetylcholine receptor agonist carbachol, thus demonstrating the direct role played by this receptor in neuron nuclei maturation. Conversely, a treatment of 2/4 cells with the muscarinic receptor antagonist atropine resulted in the reduction of the amount of Lmna RNA. Finally, the hypothesis that Lmna gene product might play a crucial role in the ChAT-dependent molecular differentiation cascade was strongly supported by Lmna knockdown in 2/4 cells leading to the downregulation of genes involved in differentiation and cytoskeleton formation and to the upregulation of genes known to regulate self-renewal and stemness.

Differential requirements for Tousled-like kinases 1 and 2 in mammalian development

DEFF Research Database (Denmark)

Segura-Bayona, Sandra; Knobel, Philip A.; Gonzalez-Buron, Helena

2017-01-01

, RNA interference, cell cycle progression, viral latency, chromosome segregation and mitosis. However, little is known about the functions of TLK activity in vivo or the relative functions of the highly similar TLK1 and TLK2 in any cell type. To begin to address this, we have generated Tlk1- and Tlk2......-deficient mice. We found that while TLK1 was dispensable for murine viability, TLK2 loss led to late embryonic lethality because of placental failure. TLK2 was required for normal trophoblast differentiation and the phosphorylation of ASF1 was reduced in placentas lacking TLK2. Conditional bypass...... of the placental phenotype allowed the generation of apparently healthy Tlk2-deficient mice, while only the depletion of both TLK1 and TLK2 led to extensive genomic instability, indicating that both activities contribute to genome maintenance. Our data identifies a specific role for TLK2 in placental function...

Introduction to fractional and pseudo-differential equations with singular symbols

CERN Document Server

Umarov, Sabir

2015-01-01

The book systematically presents the theories of pseudo-differential operators with symbols singular in dual variables, fractional order derivatives, distributed and variable order fractional derivatives, random walk approximants, and applications of these theories to various initial and multi-point boundary value problems for pseudo-differential equations. Fractional Fokker-Planck-Kolmogorov equations associated with a large class of stochastic processes are presented. A complex version of the theory of pseudo-differential operators with meromorphic symbols based on the recently introduced complex Fourier transform is developed and applied for initial and boundary value problems for systems of complex differential and pseudo-differential equations.

Comparison differential transformation technique with Adomian decomposition method for linear and nonlinear initial value problems

International Nuclear Information System (INIS)

Abdel-Halim Hassan, I.H.

2008-01-01

In this paper, we will compare the differential transformation method DTM and Adomian decomposition method ADM to solve partial differential equations (PDEs). The definition and operations of differential transform method was introduced by Zhou [Zhou JK. Differential transformation and its application for electrical circuits. Wuuhahn, China: Huarjung University Press; 1986 [in Chinese

Numerical differential protection

CERN Document Server

Ziegler, Gerhard

2012-01-01

Differential protection is a fast and selective method of protection against short-circuits. It is applied in many variants for electrical machines, trans?formers, busbars, and electric lines.Initially this book covers the theory and fundamentals of analog and numerical differential protection. Current transformers are treated in detail including transient behaviour, impact on protection performance, and practical dimensioning. An extended chapter is dedicated to signal transmission for line protection, in particular, modern digital communication and GPS timing.The emphasis is then pla

Vacuum type D initial data

Science.gov (United States)

García-Parrado Gómez-Lobo, Alfonso

2016-09-01

A vacuum type D initial data set is a vacuum initial data set of the Einstein field equations whose data development contains a region where the space–time is of Petrov type D. In this paper we give a systematic characterisation of a vacuum type D initial data set. By systematic we mean that the only quantities involved are those appearing in the vacuum constraints, namely the first fundamental form (Riemannian metric) and the second fundamental form. Our characterisation is a set of conditions consisting of the vacuum constraints and some additional differential equations for the first and second fundamental forms These conditions can be regarded as a system of partial differential equations on a Riemannian manifold and the solutions of the system contain all possible regular vacuum type D initial data sets. As an application we particularise our conditions for the case of vacuum data whose data development is a subset of the Kerr solution. This has applications in the formulation of the nonlinear stability problem of the Kerr black hole.

Dynamic crack initiation toughness : experiments and peridynamic modeling.

Energy Technology Data Exchange (ETDEWEB)

Foster, John T.

2009-10-01

This is a dissertation on research conducted studying the dynamic crack initiation toughness of a 4340 steel. Researchers have been conducting experimental testing of dynamic crack initiation toughness, K{sub Ic}, for many years, using many experimental techniques with vastly different trends in the results when reporting K{sub Ic} as a function of loading rate. The dissertation describes a novel experimental technique for measuring K{sub Ic} in metals using the Kolsky bar. The method borrows from improvements made in recent years in traditional Kolsky bar testing by using pulse shaping techniques to ensure a constant loading rate applied to the sample before crack initiation. Dynamic crack initiation measurements were reported on a 4340 steel at two different loading rates. The steel was shown to exhibit a rate dependence, with the recorded values of K{sub Ic} being much higher at the higher loading rate. Using the knowledge of this rate dependence as a motivation in attempting to model the fracture events, a viscoplastic constitutive model was implemented into a peridynamic computational mechanics code. Peridynamics is a newly developed theory in solid mechanics that replaces the classical partial differential equations of motion with integral-differential equations which do not require the existence of spatial derivatives in the displacement field. This allows for the straightforward modeling of unguided crack initiation and growth. To date, peridynamic implementations have used severely restricted constitutive models. This research represents the first implementation of a complex material model and its validation. After showing results comparing deformations to experimental Taylor anvil impact for the viscoplastic material model, a novel failure criterion is introduced to model the dynamic crack initiation toughness experiments. The failure model is based on an energy criterion and uses the K{sub Ic} values recorded experimentally as an input. The failure model

Solving Differential Equations in R: Package deSolve

Science.gov (United States)

In this paper we present the R package deSolve to solve initial value problems (IVP) written as ordinary differential equations (ODE), differential algebraic equations (DAE) of index 0 or 1 and partial differential equations (PDE), the latter solved using the method of lines appr...

Brain Sexual Differentiation and Requirement of SRY: Why or Why Not?

OpenAIRE

Rosenfeld, Cheryl S.

2017-01-01

Brain sexual differentiation is orchestrated by precise coordination of sex steroid hormones. In some species, programming of select male brain regions is dependent upon aromatization of testosterone to estrogen. In mammals, these hormones surge during the organizational and activational periods that occur during perinatal development and adulthood, respectively. In various fish and reptiles, incubation temperature during a critical embryonic period results in male or female sexual differenti...

Asymmetric division and differential gene expression during a bacterial developmental program requires DivIVA.

Directory of Open Access Journals (Sweden)

Prahathees Eswaramoorthy

2014-08-01

Full Text Available Sporulation in the bacterium Bacillus subtilis is a developmental program in which a progenitor cell differentiates into two different cell types, the smaller of which eventually becomes a dormant cell called a spore. The process begins with an asymmetric cell division event, followed by the activation of a transcription factor, σF, specifically in the smaller cell. Here, we show that the structural protein DivIVA localizes to the polar septum during sporulation and is required for asymmetric division and the compartment-specific activation of σF. Both events are known to require a protein called SpoIIE, which also localizes to the polar septum. We show that DivIVA copurifies with SpoIIE and that DivIVA may anchor SpoIIE briefly to the assembling polar septum before SpoIIE is subsequently released into the forespore membrane and recaptured at the polar septum. Finally, using super-resolution microscopy, we demonstrate that DivIVA and SpoIIE ultimately display a biased localization on the side of the polar septum that faces the smaller compartment in which σF is activated.

Quantum control for initiation and detection of explosives

International Nuclear Information System (INIS)

Greenfield, Margo T.; McGrane, Shawn D.; Scharff, R. Jason; Moore, David S.

2010-01-01

We employ quantum control methods towards detection and quantum controlled initiation (QCI) of energetic materials. Ultrafast pulse shaping of broadband Infrared (∼750 nm to 850 run) and ultraviolet (266 nm, 400 nm) light is utilized for control. The underlying principals behind optimal control can be utilized to both detect and initiate explosives. In each case, time dependent phase shaped electric fields drive the chemical systems towards a desired state. For optimal dynamic detection of explosives (ODD-Ex) a phase specific broadband infrared pulse is created which increases not only the sensitivity of detection but also the selectivity of an explosive's spectral signatures in a background of interferents. QCI on the other hand, seeks to initiate explosives by employing shaped ultraviolet light. QCI is ideal for use with explosive detonators as it removes the possibility of unintentional initiation from an electrical source while adding an additional safety feature, initiation only with the proper pulse shape. Quantum control experiments require: (1) the ability to phase and amplitude shape the laser pulse and (2) the ability to effectively search for the pulse shape which controls the reaction. In these adaptive experiments we utilize both global and local optimization search routines such as genetic algorithm, differential evolution, and downhill simplex. Pulse shaping the broadband IR light, produced by focusing 800 nm light through a pressurized tube of Argon, is straightforward as commercial pulse shapers are available at and around 800 nm. Pulse shaping in the UV requires a home built shaper. Our system is an acoustic optical modulator (AOM) pulse shaper in which consists of a fused silica AOM crystal placed in the Fourier plane of a 4-f zero dispersion compressor.

E2F6: a member of the E2F family that does not modulate squamous differentiation

International Nuclear Information System (INIS)

Wong, C.F.; Barnes, Liam M.; Smith, Louise; Popa, Claudia; Serewko-Auret, Magdalena M.; Saunders, Nicholas A.

2004-01-01

The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members

On Analytical Solutions of the Fractional Differential Equation with Uncertainty: Application to the Basset Problem

Directory of Open Access Journals (Sweden)

Soheil Salahshour

2015-02-01

Full Text Available In this paper, we apply the concept of Caputo’s H-differentiability, constructed based on the generalized Hukuhara difference, to solve the fuzzy fractional differential equation (FFDE with uncertainty. This is in contrast to conventional solutions that either require a quantity of fractional derivatives of unknown solution at the initial point (Riemann–Liouville or a solution with increasing length of their support (Hukuhara difference. Then, in order to solve the FFDE analytically, we introduce the fuzzy Laplace transform of the Caputo H-derivative. To the best of our knowledge, there is limited research devoted to the analytical methods to solve the FFDE under the fuzzy Caputo fractional differentiability. An analytical solution is presented to confirm the capability of the proposed method.

Solving Differential Equations in R: Package deSolve

NARCIS (Netherlands)

Soetaert, K.E.R.; Petzoldt, T.; Setzer, R.W.

2010-01-01

In this paper we present the R package deSolve to solve initial value problems (IVP) written as ordinary differential equations (ODE), differential algebraic equations (DAE) of index 0 or 1 and partial differential equations (PDE), the latter solved using the method of lines approach. The

Spectrally accurate initial data in numerical relativity

Science.gov (United States)

Battista, Nicholas A.

Einstein's theory of general relativity has radically altered the way in which we perceive the universe. His breakthrough was to realize that the fabric of space is deformable in the presence of mass, and that space and time are linked into a continuum. Much evidence has been gathered in support of general relativity over the decades. Some of the indirect evidence for GR includes the phenomenon of gravitational lensing, the anomalous perihelion of mercury, and the gravitational redshift. One of the most striking predictions of GR, that has not yet been confirmed, is the existence of gravitational waves. The primary source of gravitational waves in the universe is thought to be produced during the merger of binary black hole systems, or by binary neutron stars. The starting point for computer simulations of black hole mergers requires highly accurate initial data for the space-time metric and for the curvature. The equations describing the initial space-time around the black hole(s) are non-linear, elliptic partial differential equations (PDE). We will discuss how to use a pseudo-spectral (collocation) method to calculate the initial puncture data corresponding to single black hole and binary black hole systems.

Cyclic AMP (cAMP)-mediated stimulation of adipocyte differentiation requires the synergistic action of Epac- and cAMP-dependent protein kinase-dependent processes

DEFF Research Database (Denmark)

Petersen, Rasmus Koefoed; Madsen, Lise; Pedersen, Lone Møller

2008-01-01

AMP-dependent stimulation of adipocyte differentiation. Epac, working via Rap, acted synergistically with cAMP-dependent protein kinase (protein kinase A [PKA]) to promote adipogenesis. The major role of PKA was to down-regulate Rho and Rho-kinase activity, rather than to enhance CREB phosphorylation. Suppression of Rho......-kinase impaired proadipogenic insulin/insulin-like growth factor 1 signaling, which was restored by activation of Epac. This interplay between PKA and Epac-mediated processes not only provides novel insight into the initiation and tuning of adipocyte differentiation, but also demonstrates a new mechanism of c......AMP signaling whereby cAMP uses both PKA and Epac to achieve an appropriate cellular response....

The death effector domains of caspase-8 induce terminal differentiation.

Directory of Open Access Journals (Sweden)

Ainhoa Mielgo

2009-11-01

Full Text Available The differentiation and senescence programs of metazoans play key roles in regulating normal development and preventing aberrant cell proliferation, such as cancer. These programs are intimately associated with both the mitotic and apoptotic pathways. Caspase-8 is an apical apoptotic initiator that has recently been appreciated to coordinate non-apoptotic roles in the cell. Most of these functions are attributed to the catalytic domain, however, the amino-terminal death effector domains (DEDs, which belong to the death domain superfamily of proteins, can also play key roles during development. Here we describe a novel role for caspase-8 DEDs in regulating cell differentiation and senescence. Caspase-8 DEDs accumulate during terminal differentiation and senescence of epithelial, endothelial and myeloid cells; genetic deletion or shRNA suppression of caspase-8 disrupts cell differentiation, while re-expression of DEDs rescues this phenotype. Among caspase-8 deficient neuroblastoma cells, DED expression attenuated tumor growth in vivo and proliferation in vitro via disruption of mitosis and cytokinesis, resulting in upregulation of p53 and induction of differentiation markers. These events occur independent of caspase-8 catalytic activity, but require a critical lysine (K156 in a microtubule-binding motif in the second DED domain. The results demonstrate a new function for the DEDs of caspase-8, and describe an unexpected mechanism that contributes to cell differentiation and senescence.

Licensing requirements for initial commissioning programs in Spain: Application to different PWR designs

International Nuclear Information System (INIS)

Munuera, A.; Conde, J.M.; Martinez, J.

1991-01-01

This paper describes the overall licensing process in Spain, focusing on the initial commissioning requirements. The significance of this part of the regulatory work is evident both from the licensing and the licensee's points of view. Licensing in Spain is ruled by different laws which determine the general requirements and fix the licensing frame. Being a nuclear technology importer country, the base of the regulatory work lies on the rules and regulations of the country of origin of the planet, with the addition of case specific requirements. The application of this methodology to plants designed in different countries produces licensing processes which are similar to the overall, but very different in its development. It also means a special technical effort on the part of the regulatory body to cope with the problems arising from the use of different technologies and safety standards. The start-up programs from fuel loading to full power of a Westinghouse plant (Vandellos 2) and a Siemens-KWU plant (Trillo 1) are compared from the technical point of view, enhancing the differences that can be relevant for the regulatory work. The difficulties arising from the application of both the German and US concepts are discussed. (orig.)

Actin-associated protein palladin is required for migration behavior and differentiation potential of C2C12 myoblast cells

Energy Technology Data Exchange (ETDEWEB)

Nguyen, Ngoc Uyen Nhi; Liang, Vincent Roderick; Wang, Hao-Ven, E-mail: hvwang@mail.ncku.edu.tw

2014-09-26

Highlights: • Palladin is involved in myogenesis in vitro. • Palladin knockdown by siRNA increases myoblast proliferation, viability and differentiation. • Palladin knockdown decreases C2C12 myoblast migration ability. - Abstract: The actin-associated protein palladin has been shown to be involved in differentiation processes in non-muscle tissues. However, but its function in skeletal muscle has rarely been studied. Palladin plays important roles in the regulation of diverse actin-related signaling in a number of cell types. Since intact actin-cytoskeletal remodeling is necessary for myogenesis, in the present study, we pursue to investigate the role of actin-associated palladin in skeletal muscle differentiation. Palladin in C2C12 myoblasts is knocked-down using specific small interfering RNA (siRNA). The results show that down-regulation of palladin decreased migratory activity of mouse skeletal muscle C2C12 myoblasts. Furthermore, the depletion of palladin enhances C2C12 vitality and proliferation. Of note, the loss of palladin promotes C2C12 to express the myosin heavy chain, suggesting that palladin has a role in the modulation of C2C12 differentiation. It is thus proposed that palladin is required for normal C2C12 myogenesis in vitro.

Actin-associated protein palladin is required for migration behavior and differentiation potential of C2C12 myoblast cells

International Nuclear Information System (INIS)

Nguyen, Ngoc Uyen Nhi; Liang, Vincent Roderick; Wang, Hao-Ven

2014-01-01

Highlights: • Palladin is involved in myogenesis in vitro. • Palladin knockdown by siRNA increases myoblast proliferation, viability and differentiation. • Palladin knockdown decreases C2C12 myoblast migration ability. - Abstract: The actin-associated protein palladin has been shown to be involved in differentiation processes in non-muscle tissues. However, but its function in skeletal muscle has rarely been studied. Palladin plays important roles in the regulation of diverse actin-related signaling in a number of cell types. Since intact actin-cytoskeletal remodeling is necessary for myogenesis, in the present study, we pursue to investigate the role of actin-associated palladin in skeletal muscle differentiation. Palladin in C2C12 myoblasts is knocked-down using specific small interfering RNA (siRNA). The results show that down-regulation of palladin decreased migratory activity of mouse skeletal muscle C2C12 myoblasts. Furthermore, the depletion of palladin enhances C2C12 vitality and proliferation. Of note, the loss of palladin promotes C2C12 to express the myosin heavy chain, suggesting that palladin has a role in the modulation of C2C12 differentiation. It is thus proposed that palladin is required for normal C2C12 myogenesis in vitro

Noninfectious differential diagnoses of pneumonia

International Nuclear Information System (INIS)

Wielandner, A.; Toelly, A.; Agarwal, P.; Bardach, C.

2017-01-01

In patients with a clinical suspicion of pneumonia, typical clinical and laboratory features along with the detection of infiltrates on chest X-ray are as a rule considered diagnostic and therapy is immediately initiated; however, studies have shown that in up to 5% of patients with an initial suspicion of pneumonia, another noninfectious pulmonary disease was the underlying cause. Early recognition and differentiation of diseases mimicking pneumonia are prerequisites for an adequate therapy. The aim of this review is to present the important noninfectious differential diagnoses of pneumonia and to provide the reader with tools for a systematic diagnostic approach. A literature search was carried out. As alterations in the lungs often result in similar imaging appearances and a differentiation between transudates, exsudates, blood and cells is not feasible by chest X-ray or CT, a systematic approach is essential to make an appropriate diagnosis. Hence, consideration of the temporal course, predominant pattern, distribution of findings, additional findings and clinical presentation are indispensable. (orig.) [de

Nonlinear differential equations

Energy Technology Data Exchange (ETDEWEB)

Dresner, L.

1988-01-01

This report is the text of a graduate course on nonlinear differential equations given by the author at the University of Wisconsin-Madison during the summer of 1987. The topics covered are: direction fields of first-order differential equations; the Lie (group) theory of ordinary differential equations; similarity solutions of second-order partial differential equations; maximum principles and differential inequalities; monotone operators and iteration; complementary variational principles; and stability of numerical methods. The report should be of interest to graduate students, faculty, and practicing scientists and engineers. No prior knowledge is required beyond a good working knowledge of the calculus. The emphasis is on practical results. Most of the illustrative examples are taken from the fields of nonlinear diffusion, heat and mass transfer, applied superconductivity, and helium cryogenics.

Nonlinear differential equations

International Nuclear Information System (INIS)

Dresner, L.

1988-01-01

This report is the text of a graduate course on nonlinear differential equations given by the author at the University of Wisconsin-Madison during the summer of 1987. The topics covered are: direction fields of first-order differential equations; the Lie (group) theory of ordinary differential equations; similarity solutions of second-order partial differential equations; maximum principles and differential inequalities; monotone operators and iteration; complementary variational principles; and stability of numerical methods. The report should be of interest to graduate students, faculty, and practicing scientists and engineers. No prior knowledge is required beyond a good working knowledge of the calculus. The emphasis is on practical results. Most of the illustrative examples are taken from the fields of nonlinear diffusion, heat and mass transfer, applied superconductivity, and helium cryogenics

Induction of functional Fc receptors in P388 leukemia cells. Requirement for multiple differentiation signals.

Science.gov (United States)

Cohen, D A; Stotelmyer, N L; Kaplan, A M

1985-04-01

The development of functional Fc receptors (FcR) during induced differentiation with the tumor promoter, phorbol myristate acetate (PMA), was studied in the murine tumor cell line, P388. PMA induced the appearance of FcR on the membranes of P388 cells as indicated by the binding of IgG-coated sheep red blood cells (IgG-SRBC). Concentrations of PMA as low as 1 ng/ml were sufficient to induce the expression of FcR as well as to inhibit cellular division and to induce adherence in the P388 tumor cell line; however, optimal FcR induction occurred at PMA concentrations of 10-100 ng/ml. Immunofluorescent analysis with heat-aggregated myeloma proteins indicated that PMA induced FcR which were capable of binding IgG2a and IgG2b immunoglobulins, but not IgG1. Adherence to a substratum was determined to be a second required signal for expression of FcR, since PMA induction of P388 tumor cells in teflon dishes failed to fully develop FcR and adherence of P388 cells to poly-L-lysine-coated culture dishes in the absence of PMA was insufficient for FcR expression. FcR which appeared after PMA induction were non-functional in the sense that membrane-bound IgG-SRBC were not ingested to any significant extent by the tumor cells. However, if FcR induction occurred in the presence conA-induced rat spleen cell culture supernatants, phagocytosis of membrane-bound erythrocytes occurred. These findings suggest that for the expression of FcR which are capable of particle internalization, at least three identifiable membrane-transmitted signals are required during differentiation.

The Initial Conditions of Fractional Calculus

International Nuclear Information System (INIS)

Trigeassou, J. C.; Maamri, N.

2011-01-01

During the past fifty years , Fractional Calculus has become an original and renowned mathematical tool for the modelling of diffusion Partial Differential Equations and the design of robust control algorithms. However, in spite of these celebrated results, some theoretical problems have not yet received a satisfying solution. The mastery of initial conditions, either for Fractional Differential Equations (FDEs) or for the Caputo and Riemann-Liouville fractional derivatives, remains an open research domain. The solution of this fundamental problem, also related to the long range memory property, is certainly the necessary prerequisite for a satisfying approach to modelling and control applications. The fractional integrator and its continuously frequency distributed differential model is a valuable tool for the simulation of fractional systems and the solution of initial condition problems. Indeed, the infinite dimensional state vector of fractional integrators allows the direct generalization to fractional calculus of the theoretical results of integer order systems. After a reminder of definitions and properties related to fractional derivatives and systems, this presentation is intended to show, based on the results of two recent publications [1,2], how the fractional integrator provides the solution of the initial condition problem of FDEs and of Caputo and Riemann-Liouville fractional derivatives. Numerical simulation examples illustrate and validate these new theoretical concepts.

Solving Differential Equations Using Modified Picard Iteration

Science.gov (United States)

Robin, W. A.

2010-01-01

Many classes of differential equations are shown to be open to solution through a method involving a combination of a direct integration approach with suitably modified Picard iterative procedures. The classes of differential equations considered include typical initial value, boundary value and eigenvalue problems arising in physics and…

Post-embryonic nerve-associated precursors to adult pigment cells: genetic requirements and dynamics of morphogenesis and differentiation.

Directory of Open Access Journals (Sweden)

Erine H Budi

2011-05-01

Full Text Available The pigment cells of vertebrates serve a variety of functions and generate a stunning variety of patterns. These cells are also implicated in human pathologies including melanoma. Whereas the events of pigment cell development have been studied extensively in the embryo, much less is known about morphogenesis and differentiation of these cells during post-embryonic stages. Previous studies of zebrafish revealed genetically distinct populations of embryonic and adult melanophores, the ectotherm homologue of amniote melanocytes. Here, we use molecular markers, vital labeling, time-lapse imaging, mutational analyses, and transgenesis to identify peripheral nerves as a niche for precursors to adult melanophores that subsequently migrate to the skin to form the adult pigment pattern. We further identify genetic requirements for establishing, maintaining, and recruiting precursors to the adult melanophore lineage and demonstrate novel compensatory behaviors during pattern regulation in mutant backgrounds. Finally, we show that distinct populations of latent precursors having differential regenerative capabilities persist into the adult. These findings provide a foundation for future studies of post-embryonic pigment cell precursors in development, evolution, and neoplasia.

Comparison of two methods for customer differentiation

NARCIS (Netherlands)

A.F. Gabor (Adriana); Y. Guang (Yang); S. Axsäter (Sven)

2014-01-01

textabstractIn response to customer specific time guarantee requirements, service providers can offer differentiated ser- vices. However, conventional customer differentiation methods often lead to high holding costs and may have some practical drawbacks. We compare two customer differentiation

Costal chondrosarcoma requiring differential diagnosis from metastatic tumor.

Science.gov (United States)

Matsuoka, Katsunari; Ueda, Mitsuhiro; Miyamoto, Yoshihiro

2017-02-01

Although chondrosarcoma is a common malignant bone tumor, cases arising in the rib are relatively rare. We experienced a case of chondrosarcoma arising in the right 10th rib during follow-up after lung cancer surgery. Although the finding of an osteolytic mass suggested a metastatic bone tumor, 18F-fluorodeoxyglucose positron-emission tomography demonstrated low fluorodeoxyglucose uptake, and a primary bone tumor was suspected. The bone tumor was resected and diagnosed as chondrosarcoma. Four years after resection, there has been no recurrence or metastasis. Positron-emission tomography was useful for differential diagnosis between a chondrosarcoma and a metastatic bone tumor.

On Degenerate Partial Differential Equations

OpenAIRE

Chen, Gui-Qiang G.

2010-01-01

Some of recent developments, including recent results, ideas, techniques, and approaches, in the study of degenerate partial differential equations are surveyed and analyzed. Several examples of nonlinear degenerate, even mixed, partial differential equations, are presented, which arise naturally in some longstanding, fundamental problems in fluid mechanics and differential geometry. The solution to these fundamental problems greatly requires a deep understanding of nonlinear degenerate parti...

Spline Collocation Method for Nonlinear Multi-Term Fractional Differential Equation

OpenAIRE

Choe, Hui-Chol; Kang, Yong-Suk

2013-01-01

We study an approximation method to solve nonlinear multi-term fractional differential equations with initial conditions or boundary conditions. First, we transform the nonlinear multi-term fractional differential equations with initial conditions and boundary conditions to nonlinear fractional integral equations and consider the relations between them. We present a Spline Collocation Method and prove the existence, uniqueness and convergence of approximate solution as well as error estimatio...

Cell cycle-dependent differentiation dynamics balances growth and endocrine differentiation in the pancreas

DEFF Research Database (Denmark)

Kim, Yung Hae; Larsen, Hjalte List; Rué, Paul

2015-01-01

Organogenesis relies on the spatiotemporal balancing of differentiation and proliferation driven by an expanding pool of progenitor cells. In the mouse pancreas, lineage tracing at the population level has shown that the expanding pancreas progenitors can initially give rise to all endocrine...

Impulsive differential inclusions a fixed point approach

CERN Document Server

Ouahab, Abdelghani; Henderson, Johnny

2013-01-01

Impulsive differential equations have been developed in modeling impulsive problems in physics, population dynamics, ecology, biotechnology, industrial robotics, pharmacokinetics, optimal control, etc. The questions of existence and stability of solutions for different classes of initial values problems for impulsive differential equations and inclusions with fixed and variable moments are considered in detail. Attention is also given to boundary value problems and relative questions concerning differential equations. This monograph addresses a variety of side issues that arise from its simple

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate.

Science.gov (United States)

Moon, Mi-Young; Kim, Hyun Jung; Choi, Bo Young; Sohn, Min; Chung, Tae Nyoung; Suh, Sang Won

2018-01-01

Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs) are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30  μ M and 100  μ M of ZnCl 2 . Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin) in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Zinc Promotes Adipose-Derived Mesenchymal Stem Cell Proliferation and Differentiation towards a Neuronal Fate

Directory of Open Access Journals (Sweden)

Mi-Young Moon

2018-01-01

Full Text Available Zinc is an essential element required for cell division, migration, and proliferation. Under zinc-deficient conditions, proliferation and differentiation of neural progenitors are significantly impaired. Adipose-derived mesenchymal stem cells (AD-MSCs are multipotent stem cells that can differentiate into neurons. The aim of this study was to evaluate the effect of zinc on AD-MSC proliferation and differentiation. We initially examined the effect of zinc on stem cell proliferation at the undifferentiated stage. AD-MSCs showed high proliferation rates on day 6 in 30 μM and 100 μM of ZnCl2. Zinc chelation inhibited AD-MSC proliferation via downregulation of ERK1/2 activity. We then assessed whether zinc was involved in cell migration and neurite outgrowth during differentiation. After three days of neuronal differentiation, TUJ-1-positive cells were observed, implying that AD-MSCs had differentiated into early neuron or neuron-like cells. Neurite outgrowth was increased in the zinc-treated group, while the CaEDTA-treated group showed diminished, shrunken neurites. Furthermore, we showed that zinc promoted neurite outgrowth via the inactivation of RhoA and led to the induction of neuronal gene expression (MAP2 and nestin in differentiated stem cells. Taken together, zinc promoted AD-MSC proliferation and affected neuronal differentiation, mainly by increasing neurite outgrowth.

Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex*

Science.gov (United States)

Douglas, Max E.

2016-01-01

Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly (“G1-like”) and high affinity recruitment when CMG assembly takes place (“S-phase-like”). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. PMID:26719337

Recruitment of Mcm10 to Sites of Replication Initiation Requires Direct Binding to the Minichromosome Maintenance (MCM) Complex.

Science.gov (United States)

Douglas, Max E; Diffley, John F X

2016-03-11

Mcm10 is required for the initiation of eukaryotic DNA replication and contributes in some unknown way to the activation of the Cdc45-MCM-GINS (CMG) helicase. How Mcm10 is localized to sites of replication initiation is unclear, as current models indicate that direct binding to minichromosome maintenance (MCM) plays a role, but the details and functional importance of this interaction have not been determined. Here, we show that purified Mcm10 can bind both DNA-bound double hexamers and soluble single hexamers of MCM. The binding of Mcm10 to MCM requires the Mcm10 C terminus. Moreover, the binding site for Mcm10 on MCM includes the Mcm2 and Mcm6 subunits and overlaps that for the loading factor Cdt1. Whether Mcm10 recruitment to replication origins depends on CMG helicase assembly has been unclear. We show that Mcm10 recruitment occurs via two modes: low affinity recruitment in the absence of CMG assembly ("G1-like") and high affinity recruitment when CMG assembly takes place ("S-phase-like"). Mcm10 that cannot bind directly to MCM is defective in both modes of recruitment and is unable to support DNA replication. These findings indicate that Mcm10 is localized to replication initiation sites by directly binding MCM through the Mcm10 C terminus. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

C/EBPalpha and C/EBPbeta are required for Sebocyte differentiation and stratified squamous differentiation in adult mouse skin.

Directory of Open Access Journals (Sweden)

John S House

Full Text Available C/EBPalpha and C/EBPbeta are bZIP transcription factors that are highly expressed in the interfollicular epidermis and sebaceous glands of skin and yet germ line deletion of either family member alone has only mild or no effect on keratinocyte biology and their role in sebocyte biology has never been examined. To address possible functional redundancies and reveal functional roles of C/EBPalpha and C/EBPbeta in postnatal skin, mouse models were developed in which either family member could be acutely ablated alone or together in the epidermis and sebaceous glands of adult mice. Acute removal of either C/EBPalpha or C/EBPbeta alone in adult mouse skin revealed modest to no discernable changes in epidermis or sebaceous glands. In contrast, co-ablation of C/EBPalpha and C/EBPbeta in postnatal epidermis resulted in disruption of stratified squamous differentiation characterized by hyperproliferation of basal and suprabasal keratinocytes and a defective basal to spinous keratinocyte transition involving an expanded basal compartment and a diminished and delayed spinous compartment. Acute co-ablation of C/EBPalpha and C/EBPbeta in sebaceous glands resulted in severe morphological defects, and sebocyte differentiation was blocked as determined by lack of sebum production and reduced expression of stearoyl-CoA desaturase (SCD3 and melanocortin 5 receptor (MC5R, two markers of terminal sebocyte differentiation. Specialized sebocytes of Meibomian glands and preputial glands were also affected. Our results indicate that in adult mouse skin, C/EBPalpha and C/EBPbeta are critically involved in regulating sebocyte differentiation and epidermal homeostasis involving the basal to spinous keratinocyte transition and basal cell cycle withdrawal.

Initiation of male sperm-transfer behavior in Caenorhabditis elegans requires input from the ventral nerve cord

Directory of Open Access Journals (Sweden)

Gharib Shahla

2006-08-01

Full Text Available Abstract Background The Caenorhabditis elegans male exhibits a stereotypic behavioral pattern when attempting to mate. This behavior has been divided into the following steps: response, backing, turning, vulva location, spicule insertion, and sperm transfer. We and others have begun in-depth analyses of all these steps in order to understand how complex behaviors are generated. Here we extend our understanding of the sperm-transfer step of male mating behavior. Results Based on observation of wild-type males and on genetic analysis, we have divided the sperm-transfer step of mating behavior into four sub-steps: initiation, release, continued transfer, and cessation. To begin to understand how these sub-steps of sperm transfer are regulated, we screened for ethylmethanesulfonate (EMS-induced mutations that cause males to transfer sperm aberrantly. We isolated an allele of unc-18, a previously reported member of the Sec1/Munc-18 (SM family of proteins that is necessary for regulated exocytosis in C. elegans motor neurons. Our allele, sy671, is defective in two distinct sub-steps of sperm transfer: initiation and continued transfer. By a series of transgenic site-of-action experiments, we found that motor neurons in the ventral nerve cord require UNC-18 for the initiation of sperm transfer, and that UNC-18 acts downstream or in parallel to the SPV sensory neurons in this process. In addition to this neuronal requirement, we found that non-neuronal expression of UNC-18, in the male gonad, is necessary for the continuation of sperm transfer. Conclusion Our division of sperm-transfer behavior into sub-steps has provided a framework for the further detailed analysis of sperm transfer and its integration with other aspects of mating behavior. By determining the site of action of UNC-18 in sperm-transfer behavior, and its relation to the SPV sensory neurons, we have further defined the cells and tissues involved in the generation of this behavior. We

Initiation of male sperm-transfer behavior in Caenorhabditis elegans requires input from the ventral nerve cord.

Science.gov (United States)

Schindelman, Gary; Whittaker, Allyson J; Thum, Jian Yuan; Gharib, Shahla; Sternberg, Paul W

2006-08-15

The Caenorhabditis elegans male exhibits a stereotypic behavioral pattern when attempting to mate. This behavior has been divided into the following steps: response, backing, turning, vulva location, spicule insertion, and sperm transfer. We and others have begun in-depth analyses of all these steps in order to understand how complex behaviors are generated. Here we extend our understanding of the sperm-transfer step of male mating behavior. Based on observation of wild-type males and on genetic analysis, we have divided the sperm-transfer step of mating behavior into four sub-steps: initiation, release, continued transfer, and cessation. To begin to understand how these sub-steps of sperm transfer are regulated, we screened for ethylmethanesulfonate (EMS)-induced mutations that cause males to transfer sperm aberrantly. We isolated an allele of unc-18, a previously reported member of the Sec1/Munc-18 (SM) family of proteins that is necessary for regulated exocytosis in C. elegans motor neurons. Our allele, sy671, is defective in two distinct sub-steps of sperm transfer: initiation and continued transfer. By a series of transgenic site-of-action experiments, we found that motor neurons in the ventral nerve cord require UNC-18 for the initiation of sperm transfer, and that UNC-18 acts downstream or in parallel to the SPV sensory neurons in this process. In addition to this neuronal requirement, we found that non-neuronal expression of UNC-18, in the male gonad, is necessary for the continuation of sperm transfer. Our division of sperm-transfer behavior into sub-steps has provided a framework for the further detailed analysis of sperm transfer and its integration with other aspects of mating behavior. By determining the site of action of UNC-18 in sperm-transfer behavior, and its relation to the SPV sensory neurons, we have further defined the cells and tissues involved in the generation of this behavior. We have shown both a neuronal and non-neuronal requirement for

Introduction to complex theory of differential equations

CERN Document Server

Savin, Anton

2017-01-01

This book discusses the complex theory of differential equations or more precisely, the theory of differential equations on complex-analytic manifolds. Although the theory of differential equations on real manifolds is well known – it is described in thousands of papers and its usefulness requires no comments or explanations – to date specialists on differential equations have not focused on the complex theory of partial differential equations. However, as well as being remarkably beautiful, this theory can be used to solve a number of problems in real theory, for instance, the Poincaré balayage problem and the mother body problem in geophysics. The monograph does not require readers to be familiar with advanced notions in complex analysis, differential equations, or topology. With its numerous examples and exercises, it appeals to advanced undergraduate and graduate students, and also to researchers wanting to familiarize themselves with the subject.

The NIMA Kinase Is Required To Execute Stage-Specific Mitotic Functions after Initiation of Mitosis

Science.gov (United States)

Govindaraghavan, Meera; Lad, Alisha A.

2014-01-01

The G2-M transition in Aspergillus nidulans requires the NIMA kinase, the founding member of the Nek kinase family. Inactivation of NIMA results in a late G2 arrest, while overexpression of NIMA is sufficient to promote mitotic events independently of cell cycle phase. Endogenously tagged NIMA-GFP has dynamic mitotic localizations appearing first at the spindle pole body and then at nuclear pore complexes before transitioning to within nuclei and the mitotic spindle and back at the spindle pole bodies at mitotic exit, suggesting that it functions sequentially at these locations. Since NIMA is indispensable for mitotic entry, it has been difficult to determine the requirement of NIMA for subaspects of mitosis. We show here that when NIMA is partially inactivated, although mitosis can be initiated, a proportion of cells fail to successfully generate two daughter nuclei. We further define the mitotic defects to show that normal NIMA function is required for the formation of a bipolar spindle, nuclear pore complex disassembly, completion of chromatin segregation, and the normal structural rearrangements of the nuclear envelope required to generate two nuclei from one. In the remaining population of cells that enter mitosis with inadequate NIMA, two daughter nuclei are generated in a manner dependent on the spindle assembly checkpoint, indicating highly penetrant defects in mitotic progression without sufficient NIMA activity. This study shows that NIMA is required not only for mitotic entry but also sequentially for successful completion of stage-specific mitotic events. PMID:24186954

Hadamard-type fractional differential equations, inclusions and inequalities

CERN Document Server

Ahmad, Bashir; Ntouyas, Sotiris K; Tariboon, Jessada

2017-01-01

This book focuses on the recent development of fractional differential equations, integro-differential equations, and inclusions and inequalities involving the Hadamard derivative and integral. Through a comprehensive study based in part on their recent research, the authors address the issues related to initial and boundary value problems involving Hadamard type differential equations and inclusions as well as their functional counterparts. The book covers fundamental concepts of multivalued analysis and introduces a new class of mixed initial value problems involving the Hadamard derivative and Riemann-Liouville fractional integrals. In later chapters, the authors discuss nonlinear Langevin equations as well as coupled systems of Langevin equations with fractional integral conditions. Focused and thorough, this book is a useful resource for readers and researchers interested in the area of fractional calculus.

Double-diffusive convection and baroclinic instability in a differentially heated and initially stratified rotating system: the barostrat instability

International Nuclear Information System (INIS)

Vincze, Miklos; Borcia, Ion; Harlander, Uwe; Gal, Patrice Le

2016-01-01

A water-filled differentially heated rotating annulus with initially prepared stable vertical salinity profiles is studied in the laboratory. Based on two-dimensional horizontal particle image velocimetry data and infrared camera visualizations, we describe the appearance and the characteristics of the baroclinic instability in this original configuration. First, we show that when the salinity profile is linear and confined between two non-stratified layers at top and bottom, only two separate shallow fluid layers can be destabilized. These unstable layers appear nearby the top and the bottom of the tank with a stratified motionless zone between them. This laboratory arrangement is thus particularly interesting to model geophysical or astrophysical situations where stratified regions are often juxtaposed to convective ones. Then, for more general but stable initial density profiles, statistical measures are introduced to quantify the extent of the baroclinic instability at given depths and to analyze the connections between this depth-dependence and the vertical salinity profiles. We find that, although the presence of stable stratification generally hinders full-depth overturning, double-diffusive convection can lead to development of multicellular sideways convection in shallow layers and subsequently to a multilayered baroclinic instability. Therefore we conclude that by decreasing the characteristic vertical scale of the flow, stratification may even enhance the formation of cyclonic and anticyclonic eddies (and thus, mixing) in a local sense. (paper)

Double-diffusive convection and baroclinic instability in a differentially heated and initially stratified rotating system: the barostrat instability

Energy Technology Data Exchange (ETDEWEB)

Vincze, Miklos; Borcia, Ion; Harlander, Uwe [Department of Aerodynamics and Fluid Mechanics, Brandenburg University of Technology (BTU) Cottbus-Senftenberg, Siemens-Halske-Ring 14, D-03046 Cottbus (Germany); Gal, Patrice Le, E-mail: vincze.m@lecso.elte.hu [Institut de Recherche sur les Phénomènes Hors Equilibre, CNRS—Aix-Marseille University—Ecole Centrale Marseille, 49 rue F. Joliot-Curie, F-13384 Marseille (France)

2016-12-15

A water-filled differentially heated rotating annulus with initially prepared stable vertical salinity profiles is studied in the laboratory. Based on two-dimensional horizontal particle image velocimetry data and infrared camera visualizations, we describe the appearance and the characteristics of the baroclinic instability in this original configuration. First, we show that when the salinity profile is linear and confined between two non-stratified layers at top and bottom, only two separate shallow fluid layers can be destabilized. These unstable layers appear nearby the top and the bottom of the tank with a stratified motionless zone between them. This laboratory arrangement is thus particularly interesting to model geophysical or astrophysical situations where stratified regions are often juxtaposed to convective ones. Then, for more general but stable initial density profiles, statistical measures are introduced to quantify the extent of the baroclinic instability at given depths and to analyze the connections between this depth-dependence and the vertical salinity profiles. We find that, although the presence of stable stratification generally hinders full-depth overturning, double-diffusive convection can lead to development of multicellular sideways convection in shallow layers and subsequently to a multilayered baroclinic instability. Therefore we conclude that by decreasing the characteristic vertical scale of the flow, stratification may even enhance the formation of cyclonic and anticyclonic eddies (and thus, mixing) in a local sense. (paper)

Unraveling the proteomic profile of mice testis during the initiation of meiosis.

Science.gov (United States)

Shao, Binbin; Guo, Yueshuai; Wang, Lei; Zhou, Quan; Gao, Tingting; Zheng, Bo; Zheng, Haoyu; Zhou, Tao; Zhou, Zuomin; Guo, Xuejiang; Huang, Xiaoyan; Sha, Jiahao

2015-04-29

In mice, once primordial germ cells (PGCs) are generated, they continue to proliferate and migrate to eventually reach the future gonads. They initiate sexual differentiation after their colonization of the gonads. During this process, retinoic acid (RA) induces meiosis in the female germ cells, which proceeds to the diplotene stage of meiotic prophase I, whereas the male germ cells initiate growth arrest. After birth, meiosis is initiated in mice spermatogonia by their conversion to preleptotene spermatocytes. There are evidences showing the roles of RA in the regulation of spermatogonial differentiation and meiosis initiation. However, it is still not well known on what responds to RA and how RA signaling engages meiosis. Thus, we constructed a proteomic profile of proteins associated with meiosis onset during testis development in mouse and identified 104 differentially expressed proteins (≥1.5 folds). Bioinformatic analysis showed proteins functioning in specific cell processes. The expression patterns of five selected proteins were verified via Western blot, of which we found that Tfrc gene was RA responsive, with a RA responsive element, and could be up regulated by RA in spermatogonial stem cell (SSC) line. Taken together, the results provide an important reference profile for further functional study of meiosis initiation. Spermatogenesis involves mitosis of spermatogonia, meiosis of spermatocytes and spermiogenesis, in which meiosis is a unique event to germ cells, and not in the somatic cells. Till now, the detailed molecular mechanisms of the transition from mitosis to meiosis are still not elucidated. With high-throughput proteomic technology, it is now possible to systemically identify proteins possibly involved. With TMT-6plex based quantification, we identified 104 proteins differentially between testes without meiosis (day 8.5) and those that were meiosis initiated (day 10.5). And a well-known protein essential for meiosis initiation, stra8, was

Degree of Tissue Differentiation Dictates Susceptibility to BRAF-Driven Colorectal Cancer

Directory of Open Access Journals (Sweden)

Kevin Tong

2017-12-01

Full Text Available Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2, stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.

A new approach for evaluating water hammer including the initial state of pressurization of the installation and fluid

Directory of Open Access Journals (Sweden)

G. Kaless

2016-04-01

Full Text Available The water hammer phenomenon is well known since the 19th century, while its mathematical formulation, by means of differential equations, is due to works of researchers such us Allievi (1903 and others from the beginning of the 20th century. The equations found in the technical publications produce a strange water hammer when the initial condition is defined assuming an incompressible fluid and a rigid pipe. The correct solution requires solving the water hammer equations for the initial state. When the finite difference method is applied, the initial state is solved by means of a set of non-linear equations. A novel approach is proposed including the initial state of pressurization into the governing equations and hence simplifying the calculus of the initial conditions. Furthermore, a critical reading of the deduction of the equations is done pointing out conceptual inconsistencies and proposing corrections.

Polyclonal activation of rat B cells. I. A single mitogenic signal can stimulate proliferation, but three signals are required for differentiation

International Nuclear Information System (INIS)

Stunz, L.L.; Feldbush, T.L.

1986-01-01

A water-soluble, proteinaceous preparation derived from the cell walls of Salmonella typhimurium Re mutants has recently been tested in this laboratory for its ability to act as a mitogen for rat lymphocytes. This preparation (STM) has been found to be a potent simulator of B lymphocyte proliferation, as measured both by 3 H-TdR incorporation and by cell cycle analysis performed with flow cytofluorometry. STM stimulates approximately 50% of rat B cells to enter cycle. Previous investigations by others have shown that at least two sets of signals are required for B cell differentiation; (a) proliferation signals that may consist of both a stimulator of B cell conversion from G 0 to G 1 and growth factors, and (b) differentiation signals that probably include at least two B cell differentiation factors (BCDF). When STM was tested in a differentiation system it did not drive purified B cells to differentiate to PFC, either alone or when supplemented with a supernatant from concanavalin A-stimulated spleen cells (CAS). However, when both CAS and dextran sulfate (DXS) were supplied to the STM-stimulated cells, a large number of PFC resulted. DXT does not act by stimulating an additional, CAS-responsive B cell subset, since it has only a marginal effect upon 3 H-TdR uptake and does not increase the number of B cells in cycle when used together with STM. The authors that the two agents may be acting sequentially: STM stimulates the B cells to proliferate, and DXS drives the proliferating cells to become responsive to CAS. This suggests that the signals for B cell differentiation must consist of at least three activities: a trigger to stimulate the cells to proliferate, a factor to drive the cells to a BCDF-responsive state, and a BCDF that can drive the cells to secrete antibody

General technical requirements (GTR) for inventory monitoring systems (IMS) for the trilateral initiative

International Nuclear Information System (INIS)

Pshakin, Gennady M.; Kuleshov, I.; Shea, T.; Puckett, J.M.; Zhukov, I.; Mangan, Dennis L.; Matter, John C.; Waddoups, I.; Smathers, D.; Abhold, M.E.; Hsue, S.-T.; Chiaro, P.

2002-01-01

Pursuant to the Trilateral Initiative, the three parties (The Russian Federation, the United States, and the International Atomic Energy Agency) have been engaged in discussions concerning the structure of reliable monitoring systems for storage facilities having large inventories. The intent of these monitoring systems is to provide the capability for the IAEA to maintain continuity of knowledge in a sufficiently reliable manner that should there be equipment failure, loss of continuity of knowledge would be restricted to a small population of the inventory, and thus reinventory of the stored items would be minimized These facility-specific monitoring systems, referred to as Inventory Monitoring Systems (IMS) are to provide the principal means for the M A to assure that the containers of fissile material remain accounted under the Verification Agreements which are to be concluded between the IAEA and the Russian Federation and the lAEA and the United States for the verification of weapon-origin and other fissile material specified by each State as released from its defense programs. A technical experts working group for inventory monitoring systems has been meeting since Feb- of 2000 to formulate General Technical Requirements (GTR) for Inventory Monitoring Systems for the Trilateral Initiative. Although provisional agreement has been reached by the three parties concerning the GTR, it is considered a living document that can be updated as warranted by the three parties. This paper provides a summary of the GTR as it currently exists.

Overcoming natural replication barriers: differential helicase requirements.

Science.gov (United States)

Anand, Ranjith P; Shah, Kartik A; Niu, Hengyao; Sung, Patrick; Mirkin, Sergei M; Freudenreich, Catherine H

2012-02-01

DNA sequences that form secondary structures or bind protein complexes are known barriers to replication and potential inducers of genome instability. In order to determine which helicases facilitate DNA replication across these barriers, we analyzed fork progression through them in wild-type and mutant yeast cells, using 2-dimensional gel-electrophoretic analysis of the replication intermediates. We show that the Srs2 protein facilitates replication of hairpin-forming CGG/CCG repeats and prevents chromosome fragility at the repeat, whereas it does not affect replication of G-quadruplex forming sequences or a protein-bound repeat. Srs2 helicase activity is required for hairpin unwinding and fork progression. Also, the PCNA binding domain of Srs2 is required for its in vivo role of replication through hairpins. In contrast, the absence of Sgs1 or Pif1 helicases did not inhibit replication through structural barriers, though Pif1 did facilitate replication of a telomeric protein barrier. Interestingly, replication through a protein barrier but not a DNA structure barrier was modulated by nucleotide pool levels, illuminating a different mechanism by which cells can regulate fork progression through protein-mediated stall sites. Our analyses reveal fundamental differences in the replication of DNA structural versus protein barriers, with Srs2 helicase activity exclusively required for fork progression through hairpin structures.

Prox1 Inhibits Proliferation and Is Required for Differentiation of the Oligodendrocyte Cell Lineage in the Mouse.

Directory of Open Access Journals (Sweden)

Kentaro Kato

Full Text Available Central nervous system injury induces a regenerative response in ensheathing glial cells comprising cell proliferation, spontaneous axonal remyelination, and limited functional recovery, but the molecular mechanisms are not fully understood. In Drosophila, this involves the genes prospero and Notch controlling the balance between glial proliferation and differentiation, and manipulating their levels in glia can switch the response to injury from prevention to promotion of repair. In the mouse, Notch1 maintains NG2 oligodendrocyte progenitor cells (OPCs in a progenitor state, but what factor may enable oligodendrocyte (OL differentiation and functional remyelination is not understood. Here, we asked whether the mammalian homologue of prospero, Prox1, is involved. Our data show that Prox1 is distributed in NG2+ OPCs and in OLs in primary cultured cells, and in the mouse spinal cord in vivo. siRNA prox1 knockdown in primary OPCs increased cell proliferation, increased NG2+ OPC cell number and decreased CC1+ OL number. Prox1 conditional knockout in the OL cell lineage in mice increased NG2+ OPC cell number, and decreased CC1+ OL number. Lysolecithin-induced demyelination injury caused a reduction in CC1+ OLs in homozygous Prox1-/- conditional knockout mice compared to controls. Remarkably, Prox1-/- conditional knockout mice had smaller lesions than controls. Altogether, these data show that Prox1 is required to inhibit OPC proliferation and for OL differentiation, and could be a relevant component of the regenerative glial response. Therapeutic uses of glia and stem cells to promote regeneration and repair after central nervous system injury would benefit from manipulating Prox1.

LSODE, 1. Order Stiff or Non-Stiff Ordinary Differential Equations System Initial Value Problems

International Nuclear Information System (INIS)

Hindmarsh, A.C.; Petzold, L.R.

2005-01-01

1 - Description of program or function: LSODE (Livermore Solver for Ordinary Differential Equations) solves stiff and non-stiff systems of the form dy/dt = f. In the stiff case, it treats the Jacobian matrix df/dy as either a dense (full) or a banded matrix, and as either user-supplied or internally approximated by difference quotients. It uses Adams methods (predictor-corrector) in the non-stiff case, and Backward Differentiation Formula (BDF) methods (the Gear methods) in the stiff case. The linear systems that arise are solved by direct methods (LU factor/solve). The LSODE source is commented extensively to facilitate modification. Both a single-precision version and a double-precision version are available. 2 - Methods: It is assumed that the ODEs are given explicitly, so that the system can be written in the form dy/dt = f(t,y), where y is the vector of dependent variables, and t is the independent variable. LSODE contains two variable-order, variable- step (with interpolatory step-changing) integration methods. The first is the implicit Adams or non-stiff method, of orders one through twelve. The second is the backward differentiation or stiff method (or BDF method, or Gear's method), of orders one through five. 3 - Restrictions on the complexity of the problem: The differential equations must be given in explicit form, i.e., dy/dt = f(y,t). Problems with intermittent high-speed transients may cause inefficient or unstable performance

Signal differentiation in position tracking control of dc motors

International Nuclear Information System (INIS)

Beltran-Carbajal, F; Valderrabano-Gonzalez, A; Rosas-Caro, J C

2015-01-01

An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only

Differential marker expression by cultures rich in mesenchymal stem cells

Science.gov (United States)

2013-01-01

Background Mesenchymal stem cells have properties that make them amenable to therapeutic use. However, the acceptance of mesenchymal stem cells in clinical practice requires standardized techniques for their specific isolation. To date, there are no conclusive marker (s) for the exclusive isolation of mesenchymal stem cells. Our aim was to identify markers differentially expressed between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. We compared and contrasted the phenotype of tissue cultures in which mesenchymal stem cells are rich and rare. By initially assessing mesenchymal stem cell differentiation, we established that bone marrow and breast adipose cultures are rich in mesenchymal stem cells while, in our hands, foreskin fibroblast and olfactory tissue cultures contain rare mesenchymal stem cells. In particular, olfactory tissue cells represent non-stem cell mesenchymal cells. Subsequently, the phenotype of the tissue cultures were thoroughly assessed using immuno-fluorescence, flow-cytometry, proteomics, antibody arrays and qPCR. Results Our analysis revealed that all tissue cultures, regardless of differentiation potential, demonstrated remarkably similar phenotypes. Importantly, it was also observed that common mesenchymal stem cell markers, and fibroblast-associated markers, do not discriminate between mesenchymal stem cell and non-stem cell mesenchymal cell cultures. Examination and comparison of the phenotypes of mesenchymal stem cell and non-stem cell mesenchymal cell cultures revealed three differentially expressed markers – CD24, CD108 and CD40. Conclusion We indicate the importance of establishing differential marker expression between mesenchymal stem cells and non-stem cell mesenchymal cells in order to determine stem cell specific markers. PMID:24304471

Differential Requirements for c-Myc in Chronic Hematopoietic Hyperplasia and Acute Hematopoietic Malignancies in Pten-null Mice

Science.gov (United States)

Zhang, Jun; Xiao, Yechen; Guo, Yinshi; Breslin, Peter; Zhang, Shubin; Wei, Wei; Zhang, Zhou; Zhang, Jiwang

2011-01-01

Myeloproliferative disorders (MPDs), lymphoproliferative disorders (LPDs), acute T-lymphocytic or myeloid leukemia and T-lymphocytic lymphoma were developed in inducible Pten-knockout (Pten−/−) mice. The appearance of these multiple diseases in one animal model provides an opportunity to study the pathogenesis of multiple diseases simultaneously. To study whether Myc function is required for the development of these hematopoietic disorders in Pten−/− mice, we generated inducible Pten/Myc double-knockout mice (Pten−/−/Myc−/−). By comparing the hematopoietic phenotypes of these double-knockout mice with those of Pten−/− mice, we found that both sets of animals developed MPDs and LPDs. However, none of the compound-mutant mice developed acute leukemia or lymphoma. Interestingly, in contrast to the MPDs which developed in Pten−/− mice which are dominated by granulocytes, megakaryocytes predominate in the MPDs of Pten−/−/Myc−/− mice. Our study suggests that the deregulation of PI3K/Akt signaling in Pten−/− hematopoietic cells protects these cells from apoptotic cell death, resulting in chronic proliferative disorders. But due to the differential requirement for Myc in granulocyte as compared to megakaryocyte proliferation, Myc deletion converts Pten−/− MPDs from granulocyte-dominated to megakaryocyte-dominated conditions. Myc is absolutely required for the development of acute hematopoietic malignancies. PMID:21926961

Precise chronology of differentiation of developing human primary dentition.

Science.gov (United States)

Hu, Xuefeng; Xu, Shan; Lin, Chensheng; Zhang, Lishan; Chen, YiPing; Zhang, Yanding

2014-02-01

While correlation of developmental stage with embryonic age of the human primary dentition has been well documented, the available information regarding the differentiation timing of the primary teeth was largely based on the observation of initial mineralization and varies significantly. In this study, we aimed to document precise differentiation timing of the developing human primary dentition. We systematically examined the expression of odontogenic differentiation markers along with the formation of mineralized tissue in each developing maxillary and mandibular teeth from human embryos with well-defined embryonic age. We show that, despite that all primary teeth initiate development at the same time, odontogenic differentiation begins in the maxillary incisors at the 15th week and in the mandibular incisors at the 16th week of gestation, followed by the canine, the first primary premolar, and the second primary premolar at a week interval sequentially. Despite that the mandibular primary incisors erupt earlier than the maxillary incisors, this distal to proximal sequential differentiation of the human primary dentition coincides in general with the sequence of tooth eruption. Our results provide an accurate chronology of odontogenic differentiation of the developing human primary dentition, which could be used as reference for future studies of human tooth development.

Somatic mutation and cell differentiation in neoplastic transformation

International Nuclear Information System (INIS)

Huberman, E.; Collart, F.R.

1987-01-01

In brief, the authors suggest that tumor formation may result from continuous expression of growth facilitating genes that, as a result of irreversible changes during the initiation step, are placed under the control of genes expressed during normal differentiation. Thus, to understand carcinogenesis, we must decipher the processes that lead to the acquisition of a mature phenotype in both normal and tumor cells and characterize the growth dependency of tumor cells to inducers of cell differentiation. Furthermore, the growth of a variety of tumors may be controlled through the use of inducers of maturation that activate genes located beyond the gene that is altered during tumor initiation. 22 refs., 3 figs

On global error estimation and control for initial value problems

NARCIS (Netherlands)

J. Lang (Jens); J.G. Verwer (Jan)

2007-01-01

textabstractThis paper addresses global error estimation and control for initial value problems for ordinary differential equations. The focus lies on a comparison between a novel approach based onthe adjoint method combined with a small sample statistical initialization and the classical approach

On global error estimation and control for initial value problems

NARCIS (Netherlands)

Lang, J.; Verwer, J.G.

2007-01-01

Abstract. This paper addresses global error estimation and control for initial value problems for ordinary differential equations. The focus lies on a comparison between a novel approach based on the adjoint method combined with a small sample statistical initialization and the classical approach

Development of photovoltaic array and module safety requirements

Science.gov (United States)

1982-01-01

Safety requirements for photovoltaic module and panel designs and configurations likely to be used in residential, intermediate, and large-scale applications were identified and developed. The National Electrical Code and Building Codes were reviewed with respect to present provisions which may be considered to affect the design of photovoltaic modules. Limited testing, primarily in the roof fire resistance field was conducted. Additional studies and further investigations led to the development of a proposed standard for safety for flat-plate photovoltaic modules and panels. Additional work covered the initial investigation of conceptual approaches and temporary deployment, for concept verification purposes, of a differential dc ground-fault detection circuit suitable as a part of a photovoltaic array safety system.

Pulsed feedback defers cellular differentiation.

Directory of Open Access Journals (Sweden)

Joe H Levine

2012-01-01

Full Text Available Environmental signals induce diverse cellular differentiation programs. In certain systems, cells defer differentiation for extended time periods after the signal appears, proliferating through multiple rounds of cell division before committing to a new fate. How can cells set a deferral time much longer than the cell cycle? Here we study Bacillus subtilis cells that respond to sudden nutrient limitation with multiple rounds of growth and division before differentiating into spores. A well-characterized genetic circuit controls the concentration and phosphorylation of the master regulator Spo0A, which rises to a critical concentration to initiate sporulation. However, it remains unclear how this circuit enables cells to defer sporulation for multiple cell cycles. Using quantitative time-lapse fluorescence microscopy of Spo0A dynamics in individual cells, we observed pulses of Spo0A phosphorylation at a characteristic cell cycle phase. Pulse amplitudes grew systematically and cell-autonomously over multiple cell cycles leading up to sporulation. This pulse growth required a key positive feedback loop involving the sporulation kinases, without which the deferral of sporulation became ultrasensitive to kinase expression. Thus, deferral is controlled by a pulsed positive feedback loop in which kinase expression is activated by pulses of Spo0A phosphorylation. This pulsed positive feedback architecture provides a more robust mechanism for setting deferral times than constitutive kinase expression. Finally, using mathematical modeling, we show how pulsing and time delays together enable "polyphasic" positive feedback, in which different parts of a feedback loop are active at different times. Polyphasic feedback can enable more accurate tuning of long deferral times. Together, these results suggest that Bacillus subtilis uses a pulsed positive feedback loop to implement a "timer" that operates over timescales much longer than a cell cycle.

Fitting Nonlinear Ordinary Differential Equation Models with Random Effects and Unknown Initial Conditions Using the Stochastic Approximation Expectation-Maximization (SAEM) Algorithm.

Science.gov (United States)

Chow, Sy-Miin; Lu, Zhaohua; Sherwood, Andrew; Zhu, Hongtu

2016-03-01

The past decade has evidenced the increased prevalence of irregularly spaced longitudinal data in social sciences. Clearly lacking, however, are modeling tools that allow researchers to fit dynamic models to irregularly spaced data, particularly data that show nonlinearity and heterogeneity in dynamical structures. We consider the issue of fitting multivariate nonlinear differential equation models with random effects and unknown initial conditions to irregularly spaced data. A stochastic approximation expectation-maximization algorithm is proposed and its performance is evaluated using a benchmark nonlinear dynamical systems model, namely, the Van der Pol oscillator equations. The empirical utility of the proposed technique is illustrated using a set of 24-h ambulatory cardiovascular data from 168 men and women. Pertinent methodological challenges and unresolved issues are discussed.

The Effects of information barrier requirements on the trilateral initiative attribute measurement system (AVNG)

International Nuclear Information System (INIS)

MacArthur, D.W.; Langner, D.C.; Whiteson, R.; Wolford, J.K.

2001-01-01

Although the detection techniques used for measuring classified materials are very similar to those used in unclassified measurements, the surrounding packaging is generally very different. If iZ classified item is to be measured, an information barrier is required to protect any classified data acquired. This information barrier must protect the classified information while giving the inspector confidence that the unclassified outputs accurately reflect the classified inputs, Both information barrier and authentication considerations must be considered during all phases of system design and fabrication. One example of such a measurement system is the attribute measurement system (termed the AVNG) designed for the: Trilateral Initiative. We will discuss the integration of information barrier components into this system as well as the effects of an information barrier (including authentication) concerns on the implementation of the detector systems.

Partial differential equations

CERN Document Server

Evans, Lawrence C

2010-01-01

This text gives a comprehensive survey of modern techniques in the theoretical study of partial differential equations (PDEs) with particular emphasis on nonlinear equations. The exposition is divided into three parts: representation formulas for solutions; theory for linear partial differential equations; and theory for nonlinear partial differential equations. Included are complete treatments of the method of characteristics; energy methods within Sobolev spaces; regularity for second-order elliptic, parabolic, and hyperbolic equations; maximum principles; the multidimensional calculus of variations; viscosity solutions of Hamilton-Jacobi equations; shock waves and entropy criteria for conservation laws; and, much more.The author summarizes the relevant mathematics required to understand current research in PDEs, especially nonlinear PDEs. While he has reworked and simplified much of the classical theory (particularly the method of characteristics), he primarily emphasizes the modern interplay between funct...

Rethinking pedagogy for second-order differential equations: a simplified approach to understanding well-posed problems

Science.gov (United States)

Tisdell, Christopher C.

2017-07-01

Knowing an equation has a unique solution is important from both a modelling and theoretical point of view. For over 70 years, the approach to learning and teaching 'well posedness' of initial value problems (IVPs) for second- and higher-order ordinary differential equations has involved transforming the problem and its analysis to a first-order system of equations. We show that this excursion is unnecessary and present a direct approach regarding second- and higher-order problems that does not require an understanding of systems.

DDASAC, Double-Precision Differential or Algebraic Sensitivity Analysis

International Nuclear Information System (INIS)

Caracotsios, M.; Stewart, W.E.; Petzold, L.

1997-01-01

1 - Description of program or function: DDASAC solves nonlinear initial-value problems involving stiff implicit systems of ordinary differential and algebraic equations. Purely algebraic nonlinear systems can also be solved, given an initial guess within the region of attraction of a solution. Options include automatic reconciliation of inconsistent initial states and derivatives, automatic initial step selection, direct concurrent parametric sensitivity analysis, and stopping at a prescribed value of any user-defined functional of the current solution vector. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the sensitivities on request. 2 - Method of solution: Reconciliation of initial conditions is done with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithm of Shampine (1987), extended here to differential-algebraic equation systems. The solution is continued with the DASSL predictor- corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase detected and with row scaling of the Jacobian added. The backward-difference formulas for the predictor and corrector are expressed in divide-difference form, and the fixed-leading-coefficient form of the corrector (Jackson and Sacks-Davis 1980, Brenan et al. 1989) is used. Weights for error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations as given by Catacotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigns the work array lengths and the output unit. The machine number range and precision are determined at run time by a

Nonlocal quasilinear damped differential inclusions

Directory of Open Access Journals (Sweden)

Mouffak Benchohra

2002-01-01

Full Text Available In this paper we investigate the existence of mild solutions to second order initial value problems for a class of damped differential inclusions with nonlocal conditions. By using suitable fixed point theorems, we study the case when the multivalued map has convex and nonconvex values.

Dicer is required for haploid male germ cell differentiation in mice.

Directory of Open Access Journals (Sweden)

Hanna M Korhonen

Full Text Available BACKGROUND: The RNase III endonuclease Dicer is an important regulator of gene expression that processes microRNAs (miRNAs and small interfering RNAs (siRNAs. The best-characterized function of miRNAs is gene repression at the post-transcriptional level through the pairing with mRNAs of protein-encoding genes. Small RNAs can also act at the transcriptional level by controlling the epigenetic status of chromatin. Dicer and other mediators of small RNA pathways are present in mouse male germ cells, and several miRNAs and endogenous siRNAs are expressed in the testis, suggesting that Dicer-dependent small RNAs are involved in the control of the precisely timed and highly organised process of spermatogenesis. PRINCIPAL FINDINGS: Being interested in the Dicer-mediated functions during spermatogenesis, we have analysed here a male germ cell-specific Dicer1 knockout mouse model, in which the deletion of Dicer1 takes place during early postnatal development in spermatogonia. We found that Dicer1 knockout testes were reduced in size and spermatogenesis within the seminiferous tubules was disrupted. Dicer1 knockout epididymides contained very low number of mature sperm with pronounced morphological abnormalities. Spermatogonial differentiation appeared unaffected. However, the number of haploid cells was decreased in knockout testes, and an increased number of apoptotic spermatocytes was observed. The most prominent defects were found during late haploid differentiation, and Dicer was demonstrated to be critical for the normal organization of chromatin and nuclear shaping of elongating spermatids. CONCLUSIONS/SIGNIFICANCE: We demonstrate that Dicer and Dicer-dependent small RNAs are imperative regulators of haploid spermatid differentiation and essential for male fertility.

LOFT differential pressure uncertainty analysis

International Nuclear Information System (INIS)

Evans, R.P.; Biladeau, G.L.; Quinn, P.A.

1977-03-01

A performance analysis of the LOFT differential pressure (ΔP) measurement is presented. Along with completed descriptions of test programs and theoretical studies that have been conducted on the ΔP, specific sources of measurement uncertainty are identified, quantified, and combined to provide an assessment of the ability of this measurement to satisfy the SDD 1.4.1C (June 1975) requirement of measurement of differential pressure

Expression of osterix Is Regulated by FGF and Wnt/β-Catenin Signalling during Osteoblast Differentiation.

Directory of Open Access Journals (Sweden)

Katharina Felber

Full Text Available Osteoblast differentiation from mesenchymal cells is regulated by multiple signalling pathways. Here we have analysed the roles of Fibroblast Growth Factor (FGF and canonical Wingless-type MMTV integration site (Wnt/β-Catenin signalling pathways on zebrafish osteogenesis. We have used transgenic and chemical interference approaches to manipulate these pathways and have found that both pathways are required for osteoblast differentiation in vivo. Our analysis of bone markers suggests that these pathways act at the same stage of differentiation to initiate expression of the osteoblast master regulatory gene osterix (osx. We use two independent approaches that suggest that osx is a direct target of these pathways. Firstly, we manipulate signalling and show that osx gene expression responds with similar kinetics to that of known transcriptional targets of the FGF and Wnt pathways. Secondly, we have performed ChIP with transcription factors for both pathways and our data suggest that a genomic region in the first intron of osx mediates transcriptional activation. Based upon these data, we propose that FGF and Wnt/β-Catenin pathways act in part by directing transcription of osx to promote osteoblast differentiation at sites of bone formation.

Who is a self-initiated expatriate?

DEFF Research Database (Denmark)

Cerdin, Jean-Luc; Selmer, Jan

2014-01-01

The purpose of this article is to enhance the conceptual coherence of the notion of a self-initiated expatriate (SIE). We propose a definition based on a set of conceptual criteria which differentiates SIEs from other types of international movers. This article defines who an SIE is according...

Primary central nervous system lymphoma and atypical glioblastoma: differentiation using the initial area under the curve derived from dynamic contrast-enhanced MR and the apparent diffusion coefficient

International Nuclear Information System (INIS)

Choi, Yoon Seong; Lee, Ho-Joon; Ahn, Sung Soo; Lee, Seung-Koo; Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun; Kim, Se Hoon

2017-01-01

To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P < 0.05 for all). The ICC was 0.96 for p90 of IAUC30. The IAUC may be a useful parameter together with ADC for differentiating between PCNSL and atypical GBM. (orig.)

Primary central nervous system lymphoma and atypical glioblastoma: differentiation using the initial area under the curve derived from dynamic contrast-enhanced MR and the apparent diffusion coefficient

Energy Technology Data Exchange (ETDEWEB)

Choi, Yoon Seong; Lee, Ho-Joon; Ahn, Sung Soo; Lee, Seung-Koo [Yonsei University College of Medicine, Department of Radiology and Research Institute of Radiological Science, Seodaemun-gu, Seoul (Korea, Republic of); Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun [Yonsei University College of Medicine, Department of Neurosurgery, Seoul (Korea, Republic of); Kim, Se Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of)

2017-04-15

To evaluate the ability of the initial area under the curve (IAUC) derived from dynamic contrast-enhanced MR imaging (DCE-MRI) and apparent diffusion coefficient (ADC) in differentiating between primary central nervous system lymphoma (PCNSL) and atypical glioblastoma (GBM). We retrospectively identified 19 patients with atypical GBM (less than 13 % necrosis of the enhancing tumour), and 23 patients with PCNSL. The histogram parameters of IAUC at 30, 60, 90 s (IAUC30, IAUC60, and IAUC90), and ADC were compared between PCNSL and GBM. The diagnostic performances and added values of the IAUC and ADC for differentiating between PCNSL and GBM were evaluated. Interobserver agreement was assessed via intraclass correlation coefficient (ICC). The IAUC and ADC parameters were higher in GBM than in PCNSL. The 90th percentile (p90) of IAUC30 and 10th percentile (p10) of ADC showed the best diagnostic performance. Adding p90 of IAUC30 to p10 of ADC improved the differentiation between PCNSL and GBM (area under the ROC curve [AUC] = 0.886), compared to IAUC30 or ADC alone (AUC = 0.789 and 0.744; P < 0.05 for all). The ICC was 0.96 for p90 of IAUC30. The IAUC may be a useful parameter together with ADC for differentiating between PCNSL and atypical GBM. (orig.)

Differential operators in a Clifford analysis associated to differential equations with anti-monogenic right-hand sides

International Nuclear Information System (INIS)

Nguyen Thanh Van

2006-12-01

This paper deals with the initial value problem of the type φw / φt = L (t, x, w, φw / φx i ) (1) w(0, x) = φ(x) (2) where t is the time, L is a linear first order operator in a Clifford Analysis and φ is a generalized monogenic function. We give sufficient conditions on the coefficients of operator L under which L is associated to differential equations with anti-monogenic right-hand sides. For such operator L the initial problem (1),(2) is solvable for an arbitrary generalized monogenic initial function φ and the solution is also generalized monogenic for each t. (author)

The Yekaterinburg headache initiative

DEFF Research Database (Denmark)

Lebedeva, Elena R; Olesen, Jes; Osipova, Vera V

2013-01-01

for a demonstrational interventional project in Russia, undertaken within the Global Campaign against Headache. The initiative proposes three actions: 1) raise awareness of need for improvement; 2) design and implement a three-tier model (from primary care to a single highly specialized centre with academic affiliation......) for efficient and equitable delivery of headache-related health care; 3) develop a range of educational initiatives aimed at primary-care physicians, non-specialist neurologists, pharmacists and the general public to support the second action. RESULTS AND CONCLUSION: We set these proposals in a context...... of a health-care needs assessment, and as a model for all Russia. We present and discuss early progress of the initiative, justify the investment of resources required for implementation and call for the political support that full implementation requires. The more that the Yekaterinburg headache initiative...

School Leadership Actions to Support Differentiated Instruction

Science.gov (United States)

Byars, Jennifer Pallon

2011-01-01

Schools are required to meet a range of students' learning needs and effective school leadership is needed for the implementation of pedagogical practices responsive to the challenges of increasing student diversity and academic accountability. Literature on differentiated instruction and its constituent elements suggests differentiation results…

Application of Monte Carlo method to solving boundary value problem of differential equations

International Nuclear Information System (INIS)

Zuo Yinghong; Wang Jianguo

2012-01-01

This paper introduces the foundation of the Monte Carlo method and the way how to generate the random numbers. Based on the basic thought of the Monte Carlo method and finite differential method, the stochastic model for solving the boundary value problem of differential equations is built. To investigate the application of the Monte Carlo method to solving the boundary value problem of differential equations, the model is used to solve Laplace's equations with the first boundary condition and the unsteady heat transfer equation with initial values and boundary conditions. The results show that the boundary value problem of differential equations can be effectively solved with the Monte Carlo method, and the differential equations with initial condition can also be calculated by using a stochastic probability model which is based on the time-domain finite differential equations. Both the simulation results and theoretical analyses show that the errors of numerical results are lowered as the number of simulation particles is increased. (authors)

Global transcriptome analysis of spore formation in Myxococcus xanthus reveals a locus necessary for cell differentiation

Directory of Open Access Journals (Sweden)

Treuner-Lange Anke

2010-04-01

Full Text Available Abstract Background Myxococcus xanthus is a Gram negative bacterium that can differentiate into metabolically quiescent, environmentally resistant spores. Little is known about the mechanisms involved in differentiation in part because sporulation is normally initiated at the culmination of a complex starvation-induced developmental program and only inside multicellular fruiting bodies. To obtain a broad overview of the sporulation process and to identify novel genes necessary for differentiation, we instead performed global transcriptome analysis of an artificial chemically-induced sporulation process in which addition of glycerol to vegetatively growing liquid cultures of M. xanthus leads to rapid and synchronized differentiation of nearly all cells into myxospore-like entities. Results Our analyses identified 1 486 genes whose expression was significantly regulated at least two-fold within four hours of chemical-induced differentiation. Most of the previously identified sporulation marker genes were significantly upregulated. In contrast, most genes that are required to build starvation-induced multicellular fruiting bodies, but which are not required for sporulation per se, were not significantly regulated in our analysis. Analysis of functional gene categories significantly over-represented in the regulated genes, suggested large rearrangements in core metabolic pathways, and in genes involved in protein synthesis and fate. We used the microarray data to identify a novel operon of eight genes that, when mutated, rendered cells unable to produce viable chemical- or starvation-induced spores. Importantly, these mutants displayed no defects in building fruiting bodies, suggesting these genes are necessary for the core sporulation process. Furthermore, during the starvation-induced developmental program, these genes were expressed in fruiting bodies but not in peripheral rods, a subpopulation of developing cells which do not sporulate

Pbx and Prdm1a transcription factors differentially regulate subsets of the fast skeletal muscle program in zebrafish

Directory of Open Access Journals (Sweden)

Zizhen Yao

2013-04-01

The basic helix–loop–helix factor Myod initiates skeletal muscle differentiation by directly and sequentially activating sets of muscle differentiation genes, including those encoding muscle contractile proteins. We hypothesize that Pbx homeodomain proteins direct Myod to a subset of its transcriptional targets, in particular fast-twitch muscle differentiation genes, thereby regulating the competence of muscle precursor cells to differentiate. We have previously shown that Pbx proteins bind with Myod on the promoter of the zebrafish fast muscle gene mylpfa and that Pbx proteins are required for Myod to activate mylpfa expression and the fast-twitch muscle-specific differentiation program in zebrafish embryos. Here we have investigated the interactions of Pbx with another muscle fiber-type regulator, Prdm1a, a SET-domain DNA-binding factor that directly represses mylpfa expression and fast muscle differentiation. The prdm1a mutant phenotype, early and increased fast muscle differentiation, is the opposite of the Pbx-null phenotype, delayed and reduced fast muscle differentiation. To determine whether Pbx and Prdm1a have opposing activities on a common set of genes, we used RNA-seq analysis to globally assess gene expression in zebrafish embryos with single- and double-losses-of-function for Pbx and Prdm1a. We find that the levels of expression of certain fast muscle genes are increased or approximately wild type in pbx2/4-MO;prdm1a−/− embryos, suggesting that Pbx activity normally counters the repressive action of Prdm1a for a subset of the fast muscle program. However, other fast muscle genes require Pbx but are not regulated by Prdm1a. Thus, our findings reveal that subsets of the fast muscle program are differentially regulated by Pbx and Prdm1a. Our findings provide an example of how Pbx homeodomain proteins act in a balance with other transcription factors to regulate subsets of a cellular differentiation program.

Analyticity without Differentiability

Science.gov (United States)

Kirillova, Evgenia; Spindler, Karlheinz

2008-01-01

In this article we derive all salient properties of analytic functions, including the analytic version of the inverse function theorem, using only the most elementary convergence properties of series. Not even the notion of differentiability is required to do so. Instead, analytical arguments are replaced by combinatorial arguments exhibiting…

Service differentiation in spare parts inventory management

NARCIS (Netherlands)

Kranenburg, A.A.; Houtum, van G.J.J.A.N.

2008-01-01

The contemporary after-sales market is of increasing importance. One of the features required by the market is to provide differentiated service levels to different groups of customers. We use critical levels as a means to offer differentiation. Critical level policies aim to exploit the differences

Differentiating Science Instruction: Secondary science teachers' practices

Science.gov (United States)

Maeng, Jennifer L.; Bell, Randy L.

2015-09-01

This descriptive study investigated the implementation practices of secondary science teachers who differentiate instruction. Participants included seven high school science teachers purposefully selected from four different schools located in a mid-Atlantic state. Purposeful selection ensured participants included differentiated instruction (DI) in their lesson implementation. Data included semi-structured interviews and field notes from a minimum of four classroom observations, selected to capture the variety of differentiation strategies employed. These data were analyzed using a constant-comparative approach. Each classroom observation was scored using the validated Differentiated Instruction Implementation Matrix-Modified, which captured both the extent to which critical indicators of DI were present in teachers' instruction and the performance levels at which they engaged in these components of DI. Results indicated participants implemented a variety of differentiation strategies in their classrooms with varying proficiency. Evidence suggested all participants used instructional modifications that required little advance preparation to accommodate differences in students' interests and learning profile. Four of the seven participants implemented more complex instructional strategies that required substantial advance preparation by the teacher. Most significantly, this study provides practical strategies for in-service science teachers beginning to differentiate instruction and recommendations for professional development and preservice science teacher education.

Hyers-Ulam stability for second-order linear differential equations with boundary conditions

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Pasc Gavruta

2011-06-01

Full Text Available We prove the Hyers-Ulam stability of linear differential equations of second-order with boundary conditions or with initial conditions. That is, if y is an approximate solution of the differential equation $y''+ eta (x y = 0$ with $y(a = y(b =0$, then there exists an exact solution of the differential equation, near y.

Nielsen number and differential equations

Directory of Open Access Journals (Sweden)

Andres Jan

2005-01-01

Full Text Available In reply to a problem of Jean Leray (application of the Nielsen theory to differential equations, two main approaches are presented. The first is via Poincaré's translation operator, while the second one is based on the Hammerstein-type solution operator. The applicability of various Nielsen theories is discussed with respect to several sorts of differential equations and inclusions. Links with the Sharkovskii-like theorems (a finite number of periodic solutions imply infinitely many subharmonics are indicated, jointly with some further consequences like the nontrivial -structure of solutions of initial value problems. Some illustrating examples are supplied and open problems are formulated.

Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.

Science.gov (United States)

Slota, Leslie A; McClay, David R

2018-03-15

Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms. Copyright © 2018 Elsevier Inc. All rights reserved.

Service differentiated and adaptive CSMA/CA over IEEE 802.15.4 for Cyber-Physical Systems.

Science.gov (United States)

Xia, Feng; Li, Jie; Hao, Ruonan; Kong, Xiangjie; Gao, Ruixia

2013-01-01

Cyber-Physical Systems (CPS) that collect, exchange, manage information, and coordinate actions are an integral part of the Smart Grid. In addition, Quality of Service (QoS) provisioning in CPS, especially in the wireless sensor/actuator networks, plays an essential role in Smart Grid applications. IEEE 802.15.4, which is one of the most widely used communication protocols in this area, still needs to be improved to meet multiple QoS requirements. This is because IEEE 802.15.4 slotted Carrier Sense Multiple Access/Collision Avoidance (CSMA/CA) employs static parameter configuration without supporting differentiated services and network self-adaptivity. To address this issue, this paper proposes a priority-based Service Differentiated and Adaptive CSMA/CA (SDA-CSMA/CA) algorithm to provide differentiated QoS for various Smart Grid applications as well as dynamically initialize backoff exponent according to traffic conditions. Simulation results demonstrate that the proposed SDA-CSMA/CA scheme significantly outperforms the IEEE 802.15.4 slotted CSMA/CA in terms of effective data rate, packet loss rate, and average delay.

Local Inflammatory Cues Regulate Differentiation and Persistence of CD8+ Tissue-Resident Memory T Cells

Directory of Open Access Journals (Sweden)

Tessa Bergsbaken

2017-04-01

Full Text Available Many pathogens initiate infection at mucosal surfaces, and tissue-resident memory T (Trm cells play an important role in protective immunity, yet the tissue-specific signals that regulate Trm differentiation are poorly defined. During Yersinia infection, CD8+ T cell recruitment to areas of inflammation within the intestine is required for differentiation of the CD103−CD69+ Trm subset. Intestinal proinflammatory microenvironments have elevated interferon (IFN-β and interleukin-12 (IL-12, which regulated Trm markers, including CD103. Type I interferon-receptor- or IL-12-receptor-deficient T cells functioned similarly to wild-type (WT cells during infection; however, the inability of T cells to respond to inflammation resulted in defective differentiation of CD103−CD69+ Trm cells and reduced Trm persistence. Intestinal macrophages were the main producers of IFN-β and IL-12 during infection, and deletion of CCR2+ IL-12-producing cells reduced the size of the CD103− Trm population. These data indicate that intestinal inflammation drives phenotypic diversity and abundance of Trm cells for optimal tissue-specific immunity.

Enhancement of trophoblast differentiation and survival by low molecular weight heparin requires heparin-binding EGF-like growth factor.

Science.gov (United States)

Bolnick, Alan D; Bolnick, Jay M; Kohan-Ghadr, Hamid-Reza; Kilburn, Brian A; Pasalodos, Omar J; Singhal, Pankaj K; Dai, Jing; Diamond, Michael P; Armant, D Randall; Drewlo, Sascha

2017-06-01

Does low molecular weight heparin (LMWH) require heparin-binding epidermal growth factor (EGF)-like growth factor (HBEGF) signaling to induce extravillous trophoblast differentiation and decrease apoptosis during oxidative stress? LMWH increased HBEGF expression and secretion, and HBEGF signaling was required to stimulate trophoblast extravillous differentiation, increase invasion in vitro and reduce trophoblast apoptosis during oxidative stress. Abnormal trophoblast differentiation and survival contribute to placental insufficiency syndromes, including preeclampsia and intrauterine growth restriction. Preeclampsia often manifests as a pro-thrombotic state, with unsuccessful transformation of the spiral arteries that reduces oxygen supply and can produce placental infarction. LMWH improves placental function by increasing blood flow. Recent data suggest that the actions of LMWH transcend its anti-coagulative properties, but the molecular mechanism is unknown. There is evidence that LMWH alters the expression of human HBEGF in trophoblast cells, which regulates human trophoblast pathophysiology. HBEGF, itself, is capable of increasing trophoblast survival and invasiveness. First-trimester placental explants and the HTR-8/SVneo cell line, established using extravillous trophoblast outgrowths from first-trimester villous explants, were treated in vitro with LMWH to examine the effects on HBEGF signaling and trophoblast function under normal physiological and pathological conditions. A highly specific antagonist of HBEGF and other inhibitors of HBEGF downstream signaling were used to determine the relationship between LMWH treatment and HBEGF. Placental tissues (n = 5) were obtained with IRB approval and patient consent from first-trimester terminations. Placental explants and HTR-8/SVneo cells were cultured on plastic or Matrigel™ and treated with a therapeutic dose of LMWH (Enoxaparin; 10 IU/ml), with or without CRM197, pan Erb-B2 Receptor Tyrosine Kinase (ERBB

Fibonacci-like Differential Equations with a Polynomial Non-Homogeneous Part

NARCIS (Netherlands)

Asveld, P.R.J.

1989-01-01

We investigate non-homogeneous linear differential equations of the form $x''(t) + x'(t) - x(t) = p(t)$ where $p(t)$ is either a polynomial or a factorial polynomial in $t$. We express the solution of these differential equations in terms of the coefficients of $p(t)$, in the initial conditions, and

KRYSI, Ordinary Differential Equations Solver with Sdirk Krylov Method

International Nuclear Information System (INIS)

Hindmarsh, A.C.; Norsett, S.P.

2001-01-01

1 - Description of program or function: KRYSI is a set of FORTRAN subroutines for solving ordinary differential equations initial value problems. It is suitable for both stiff and non-stiff systems. When solving the implicit stage equations in the stiff case, KRYSI uses a Krylov subspace iteration method called the SPIGMR (Scaled Preconditioned Incomplete Generalized Minimum Residual) method. No explicit Jacobian storage is required, except where used in pre- conditioning. A demonstration problem is included with a description of two pre-conditioners that are natural for its solution by KRYSI. 2 - Method of solution: KRYSI uses a three-stage, third-order singly diagonally implicit Runge-Kutta (SDIRK) method. In the stiff case, a preconditioned Krylov subspace iteration within a (so-called) inexact Newton iteration is used to solve the system of nonlinear algebraic equations

Photon Differentials in Space and Time

DEFF Research Database (Denmark)

Schjøth, Lars; Frisvad, Jeppe Revall; Erleben, Kenny

2011-01-01

We present a novel photon mapping algorithm for animations. We extend our previous work on photon differentials [12] with time differentials. The result is a first order model of photon cones in space an time that effectively reduces the number of required photons per frame as well as efficiently...... reduces temporal aliasing without any need for in-between-frame photon maps....

Measurable Strategies in Differential Games

Science.gov (United States)

Ivanov, R. P.

1990-02-01

Nonlinear approach-evasion differential games are considered in which the initial data depend on the time. These games are investigated in the class of strategies that are functions of three variables, namely, the time, the phase variable, and the current value of the other player's control, and are measurable jointly with respect to the time and the phase variable. The ideas of the Pontryagin methods in differential games and Krasovskiĭ's ideas on extremal aiming are developed, and it is shown that measurable strategies have broad applicability. It is proved that measurable strategies are compatible with differential equations with discontinuous right-hand side, and general theorems on the existence of solving measurable strategies in approach-evasion problems are proved, along with some auxiliary assertions. It is shown that the saddle point condition in the small game ensures the existence of solving measurable strategies. An example is given. Bibliography: 14 titles.

Integrin-linked kinase is required for TGF-β1 induction of dermal myofibroblast differentiation.

Science.gov (United States)

Vi, Linda; de Lasa, Cristina; DiGuglielmo, Gianni M; Dagnino, Lina

2011-03-01

Cutaneous repair after injury requires activation of resident dermal fibroblasts and their transition to myofibroblasts. The key stimuli for myofibroblast formation are activation of transforming growth factor-β (TGF-β) receptors and mechanotransduction mediated by integrins and associated proteins. We investigated the role of integrin-linked kinase (ILK) in TGF-β1 induction of dermal fibroblast transition to myofibroblasts. ILK-deficient fibroblasts treated with TGF-β1 exhibited attenuation of Smad 2 and 3 phosphorylation, accompanied by impaired transcriptional activation of Smad targets, such as α-smooth muscle actin. These alterations were not limited to Smad-associated TGF-β1 responses, as stimulation of noncanonical mitogen-activated protein kinase pathways by this growth factor was also diminished in the absence of ILK. ILK-deficient fibroblasts exhibited abnormalities in the actin cytoskeleton, and did not form supermature focal adhesions or contractile F-actin stress fibers, indicating a severe impairment in their capacity to differentiate into myofibroblasts. These defects extended to the inability of cells to contract extracellular matrices when embedded in collagen lattices. We conclude that ILK is necessary to transduce signals implicated in the transition of dermal fibroblasts to myofibroblasts originating from matrix substrates and TGF-β1.

approximate controllability of a non-autonomous differential equation

Indian Academy of Sciences (India)

53

for a non-autonomous functional differential equation using the theory of linear ... approximate controllability of various functional differential equations in abstract ...... the operator A(t) and into the requirement that x(t) ∈ D(A) for all t ≥ 0.

MicroRNA-200c-141 and ∆Np63 are required for breast epithelial differentiation and branching morphogenesis.

Science.gov (United States)

Hilmarsdóttir, Bylgja; Briem, Eirikur; Sigurdsson, Valgardur; Franzdóttir, Sigrídur Rut; Ringnér, Markus; Arason, Ari Jon; Bergthorsson, Jon Thor; Magnusson, Magnus Karl; Gudjonsson, Thorarinn

2015-07-15

The epithelial compartment of the breast contains two lineages, the luminal- and the myoepithelial cells. D492 is a breast epithelial cell line with stem cell properties that forms branching epithelial structures in 3D culture with both luminal- and myoepithelial differentiation. We have recently shown that D492 undergo epithelial to mesenchymal transition (EMT) when co-cultured with endothelial cells. This 3D co-culture model allows critical analysis of breast epithelial lineage development and EMT. In this study, we compared the microRNA (miR) expression profiles for D492 and its mesenchymal-derivative D492M. Suppression of the miR-200 family in D492M was among the most profound changes observed. Exogenous expression of miR-200c-141 in D492M reversed the EMT phenotype resulting in gain of luminal but not myoepithelial differentiation. In contrast, forced expression of ∆Np63 in D492M restored the myoepithelial phenotype only. Co-expression of miR-200c-141 and ∆Np63 in D492M restored the branching morphogenesis in 3D culture underlining the requirement for both luminal and myoepithelial elements for obtaining full branching morphogenesis in breast epithelium. Introduction of a miR-200c-141 construct in both D492 and D492M resulted in resistance to endothelial induced EMT. In conclusion, our data suggests that expression of miR-200c-141 and ∆Np63 in D492M can reverse EMT resulting in luminal- and myoepithelial differentiation, respectively, demonstrating the importance of these molecules in epithelial integrity in the human breast. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Evaluation of accessory cell heterogeneity. I. Differential accessory cell requirement for T helper cell activation and for T-B cooperation.

Science.gov (United States)

Ramila, G; Studer, S; Kennedy, M; Sklenar, I; Erb, P

1985-01-01

Several Ia+ tumor cell lines and peritoneal exudate macrophages were tested as accessory cells (AC) for the activation of antigen-specific T cells and for T-B cooperation. The macrophages and all the Ia+ tumor lines tested induced the release of lymphokines from T cells in a major histocompatibility complex (MHC)-restricted fashion and reconstituted the antibody responses of AC-depleted spleen cells or of purified T and B cells. However, only the normal macrophages but none of the tumor lines induced carrier-specific T helper (Th) cells which help B cells for specific antihapten antibody responses by linked recognition. For T-B cooperation accessory cells were also required, but in contrast to Th cell activation any type of Ia+ AC (e.g. macrophage or tumor line) was effective. Strong MHC-restriction between the lymphocytes and the AC was seen if antigen-pulsed AC were added into the AC-depleted T-B cooperation cultures. If the AC and antigen were concomitantly added to the AC-depleted T-B cultures, MHC-restriction was less obvious. Concanavalin A supernatant reconstituted the response of AC-depleted T-B cultures provided antigen-specific Th cells and the hapten-carrier conjugate were present. If, however, tumor line-activated T cells were added instead of macrophage-induced Th cells, no cooperation with B cells took place even in the presence of Con A supernatant. The results obtained demonstrate a differential AC requirement for the induction of Th cells depending on the differentiation stage of the Th cells.

Anatomic double-bundle anterior cruciate ligament reconstruction using hamstring tendons with minimally required initial tension.

Science.gov (United States)

Mae, Tatsuo; Shino, Konsei; Matsumoto, Norinao; Natsu-Ume, Takashi; Yoneda, Kenji; Yoshikawa, Hideki; Yoneda, Minoru

2010-10-01

Our purpose was to clarify the clinical outcomes at 2 years after anatomic double-bundle anterior cruciate ligament (ACL) reconstruction with 20 N of the initial tension, which was the minimally required initial tension to perform the reconstruction successfully according to our previous report about the pre-tension necessary to restore the laxity found in the opposite knee (7.3 N; range, 2.2 to 14 N). Of 64 patients who underwent anatomic double-bundle ACL reconstruction with autogenous semitendinosus tendon, 45 were periodically examined for 2 years. Two double-looped grafts were fixed with EndoButton CL devices (Smith & Nephew Endoscopy, Andover, MA) on the femoral side and Double Spike Plates (Smith & Nephew Endoscopy) on the tibial side, while a total of 20 N of initial tension (10 N to each graft) was applied at 20° of knee flexion. The International Knee Documentation Committee Knee Examination Form and Lysholm score were used for the subjective assessment, whereas range of motion and knee stability were evaluated as the objective assessment. Grafts were evaluated in 25 patients with second-look arthroscopy. According to the International Knee Documentation Committee subjective assessment, 62% of knees were graded as normal and 38% as nearly normal. The Lysholm score was 72 points in the preoperative period and improved to 99 points at 2 years' follow-up. A loss of knee extension of less than 3° was found in 2 patients. The pivot-shift test was evaluated as negative in all patients except for 5 as a glide. KT-2000 knee arthrometer side-to-side difference (MEDmetric, San Diego, CA) was 0.1 ± 0.9 mm at 2 years' follow-up. Of the subset of grafts evaluated by second-look arthroscopy, most were considered to have good synovial coverage and to be taut. The anatomic double-bundle ACL reconstruction with 20 N of low initial tension yielded good clinical outcomes at 2 years postoperatively, and second-look arthroscopic findings were excellent. Level IV

Pseudo-differentiation syndrome

Directory of Open Access Journals (Sweden)

Dina Khalaf

2011-12-01

Full Text Available A patient with relapsed acute myeloid leukemia (AML (M2 FAB classification developed a differentiating syndrome upon receiving Decitabine therapy given with palliative intent. The patient presented with high grade fever, constitutional symptoms and severe chest symptoms with no underlying lung condition. Chest x-ray (CXR showed diffuse pulmonary infiltrates. Septic work up followed by intravenous broad spectrum antimicrobials did not improve his condition. Pan cultures’ results were repeatedly negative. Treatment with high dose Dexamethasone (DXM resulted in marked clinical and radiological improvement. Our patient initially presented with relapsed AML (M2 Fab classification with t (8; 21; negative FMS-like tyrosine kinase -internal tandem duplication (FLT3-ITD which are all good prognostic factors, yet the patient had an atypical clinical course with early frequent relapses, differentiation syndrome associated with Decitabine therapy and late in his disease, he developed a granulocytic sarcoma.

EXISTENCE AND UNIQUENESS OF SOLUTIONS TO A NONLINEAR FRACTIONAL DIFFERENTIAL EQUATION

Institute of Scientific and Technical Information of China (English)

无

2011-01-01

The initial value problem of a nonlinear fractional differential equation is discussed in this paper. Using the nonlinear alternative of Leray-Schauder type and the contraction mapping principle,we obtain the existence and uniqueness of solutions to the fractional differential equation,which extend some results of the previous papers.

Nat1 promotes translation of specific proteins that induce differentiation of mouse embryonic stem cells.

Science.gov (United States)

Sugiyama, Hayami; Takahashi, Kazutoshi; Yamamoto, Takuya; Iwasaki, Mio; Narita, Megumi; Nakamura, Masahiro; Rand, Tim A; Nakagawa, Masato; Watanabe, Akira; Yamanaka, Shinya

2017-01-10

Novel APOBEC1 target 1 (Nat1) (also known as "p97," "Dap5," and "Eif4g2") is a ubiquitously expressed cytoplasmic protein that is homologous to the C-terminal two thirds of eukaryotic translation initiation factor 4G (Eif4g1). We previously showed that Nat1-null mouse embryonic stem cells (mES cells) are resistant to differentiation. In the current study, we found that NAT1 and eIF4G1 share many binding proteins, such as the eukaryotic translation initiation factors eIF3 and eIF4A and ribosomal proteins. However, NAT1 did not bind to eIF4E or poly(A)-binding proteins, which are critical for cap-dependent translation initiation. In contrast, compared with eIF4G1, NAT1 preferentially interacted with eIF2, fragile X mental retardation proteins (FMR), and related proteins and especially with members of the proline-rich and coiled-coil-containing protein 2 (PRRC2) family. We also found that Nat1-null mES cells possess a transcriptional profile similar, although not identical, to the ground state, which is established in wild-type mES cells when treated with inhibitors of the ERK and glycogen synthase kinase 3 (GSK3) signaling pathways. In Nat1-null mES cells, the ERK pathway is suppressed even without inhibitors. Ribosome profiling revealed that translation of mitogen-activated protein kinase kinase kinase 3 (Map3k3) and son of sevenless homolog 1 (Sos1) is suppressed in the absence of Nat1 Forced expression of Map3k3 induced differentiation of Nat1-null mES cells. These data collectively show that Nat1 is involved in the translation of proteins that are required for cell differentiation.

Specialities of the differentiation conditions for the memory cells - either initial or enriched secondary cytotoxic T lymphocyte precursors (pCTL-2) specific to the MHC molecule class 1

International Nuclear Information System (INIS)

Brondz, B.D.; Osipova, T.V.; Aptikaeva, G.F.; Kronin, V.V.

1989-01-01

The in vivo induced pCTL-2 with phenotype L3T4 - Lyt2 + , specific to the H-2K b molecule, turn into effector CTLs during 4 days in the mixed lymphocyte culture (with heat-treated donor stimulators) much more efficiency when donor and recipient are different from one another not only in MHC class 1 (anti-BIO, MBR BIO.AKM) but in 1+2 (K b +1 b ) anti-C57BL/6 BIAD2(R1O1). The initial pCTL-2 differentiation in enhanced as a result of synergistic effect between the K b alloantigen and rIL2. The anti-K b pCTL-2, being separated from helper T cells by means of absorption onto the macrophage donor monolayer and elution from it, give rise to pronounced differentiation in simplified conditions, irrespective of the stimulator presence and without external rIL2. It is supposed that these phenomena are roused to secrection of the CTL differentiation factor by the eluted pCTL-2 themselves, and besides, rIL2 may promote for secretion of this factor additionally

Test set for initial value problem solvers

NARCIS (Netherlands)

W.M. Lioen (Walter); J.J.B. de Swart (Jacques)

1998-01-01

textabstractThe CWI test set for IVP solvers presents a collection of Initial Value Problems to test solvers for implicit differential equations. This test set can both decrease the effort for the code developer to test his software in a reliable way, and cross the bridge between the application

Hypoxic stress induces, but cannot sustain trophoblast stem cell differentiation to labyrinthine placenta due to mitochondrial insufficiency

Directory of Open Access Journals (Sweden)

Yufen Xie

2014-11-01

Full Text Available Dysfunctional stem cell differentiation into placental lineages is associated with gestational diseases. Of the differentiated lineages available to trophoblast stem cells (TSC, elevated O2 and mitochondrial function are necessary to placental lineages at the maternal–placental surface and important in the etiology of preeclampsia. TSC lineage imbalance leads to embryonic failure during uterine implantation. Stress at implantation exacerbates stem cell depletion by decreasing proliferation and increasing differentiation. In an implantation site O2 is normally ~2%. In culture, exposure to 2% O2 and fibroblast growth factor 4 (FGF4 enabled the highest mouse TSC multipotency and proliferation. In contrast, hypoxic stress (0.5% O2 initiated the most TSC differentiation after 24 h despite exposure to FGF4. However, hypoxic stress supported differentiation poorly after 4–7 days, despite FGF4 removal. At all tested O2 levels, FGF4 maintained Warburg metabolism; mitochondrial inactivity and aerobic glycolysis. However, hypoxic stress suppressed mitochondrial membrane potential and maintained low mitochondrial cytochrome c oxidase (oxidative phosphorylation/OxPhos, and high pyruvate kinase M2 (glycolysis despite FGF4 removal. Inhibiting OxPhos inhibited optimum differentiation at 20% O2. Moreover, adding differentiation-inducing hyperosmolar stress failed to induce differentiation during hypoxia. Thus, differentiation depended on OxPhos at 20% O2; hypoxic and hyperosmolar stresses did not induce differentiation at 0.5% O2. Hypoxia-limited differentiation and mitochondrial inhibition and activation suggest that differentiation into two lineages of the labyrinthine placenta requires O2 > 0.5–2% and mitochondrial function. Stress-activated protein kinase increases an early lineage and suppresses later lineages in proportion to the deviation from optimal O2 for multipotency, thus it is the first enzyme reported to prioritize differentiation.

Pythagoras, Binomial, and de Moivre Revisited Through Differential Equations

OpenAIRE

Singh, Jitender; Bajaj, Renu

2018-01-01

The classical Pythagoras theorem, binomial theorem, de Moivre's formula, and numerous other deductions are made using the uniqueness theorem for the initial value problems in linear ordinary differential equations.

Controlled initiation of chromosomal replication in Escherichia coli requires functional Hda protein.

Science.gov (United States)

Camara, Johanna Eltz; Skarstad, Kirsten; Crooke, Elliott

2003-05-01

Regulatory inactivation of DnaA helps ensure that the Escherichia coli chromosome is replicated only once per cell cycle, through accelerated hydrolysis of active replication initiator ATP-DnaA to inactive ADP-DnaA. Analysis of deltahda strains revealed that the regulatory inactivation of DnaA component Hda is necessary for maintaining controlled initiation but not for cell growth or viability.

Differential and Difference Boundary Value Problem for Loaded Third-Order Pseudo-Parabolic Differential Equations and Difference Methods for Their Numerical Solution

Science.gov (United States)

Beshtokov, M. Kh.

2017-12-01

Boundary value problems for loaded third-order pseudo-parabolic equations with variable coefficients are considered. A priori estimates for the solutions of the problems in the differential and difference formulations are obtained. These a priori estimates imply the uniqueness and stability of the solution with respect to the initial data and the right-hand side on a layer, as well as the convergence of the solution of each difference problem to the solution of the corresponding differential problem.

Differential forms and the geometry of general relativity

CERN Document Server

Dray, Tevian

2015-01-01

Differential Forms and the Geometry of General Relativity provides readers with a coherent path to understanding relativity. Requiring little more than calculus and some linear algebra, it helps readers learn just enough differential geometry to grasp the basics of general relativity.The book contains two intertwined but distinct halves. Designed for advanced undergraduate or beginning graduate students in mathematics or physics, most of the text requires little more than familiarity with calculus and linear algebra. The first half presents an introduction to general relativity that describes

Listeria arpJ gene modifies T helper type 2 subset differentiation.

Science.gov (United States)

Kanoh, Makoto; Maruyama, Saho; Shen, Hua; Matsumoto, Akira; Shinomiya, Hiroto; Przybilla, Karin; Gouin, Edith; Cossart, Pascale; Goebel, Werner; Asano, Yoshihiro

2015-07-15

Although the T-cell subset differentiation pathway has been characterized extensively from the view of host gene regulation, the effects of genes of the pathogen on T-cell subset differentiation during infection have yet to be elucidated. Especially, the bacterial genes that are responsible for this shift have not yet been determined. Utilizing a single-gene-mutation Listeria panel, we investigated genes involved in the host-pathogen interaction that are required for the initiation of T-cell subset differentiation in the early phase of pathogen infection. We demonstrate that the induction of T helper types 1 and 2 (Th1 and Th2) subsets are separate phenomena and are mediated by distinct Listeria genes. We identified several candidate Listeria genes that appear to be involved in the host-Listeria interaction. Among them, arpJ is the strongest candidate gene for inhibiting Th2 subset induction. Furthermore, the analysis utilizing arpJ-deficient Listeria monocytogenes (Lm) revealed that the tumor necrosis factor (TNF) superfamily (Tnfsf) 9-TNF receptor superfamily (Tnfrsf) 9 interaction inhibits the Th2 response during Lm infection. arpJ is the candidate gene for inhibiting Th2 T-cell subset induction. The arpJ gene product influences the expression of Tnfsf/Tnfrsf on antigen-presenting cells and inhibits the Th2 T-cell subset differentiation during Listeria infection. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

RIMA-dependent nuclear accumulation of IYO triggers auxin-irreversible cell differentiation in arabidopsis

NARCIS (Netherlands)

Muñoz, Alfonso; Mangano, Silvina; González-García, Mary Paz; Contreras, Ramón; Sauer, Michael; Rybel, De Bert; Weijers, Dolf; Sánchez-Serrano, José Juan; Sanmartín, Maite; Rojo, Enrique

2017-01-01

The transcriptional regulator MINIYO (IYO) is essential and rate-limiting for initiating cell differentiation in Arabidopsis thaliana. Moreover, IYO moves from the cytosol into the nucleus in cells at the meristem periphery, possibly triggering their differentiation. However, the genetic mechanisms

The timing of differentiation of adult hippocampal neurons is crucial for spatial memory.

Directory of Open Access Journals (Sweden)

Stefano Farioli-Vecchioli

2008-10-01

Full Text Available Adult neurogenesis in the dentate gyrus plays a critical role in hippocampus-dependent spatial learning. It remains unknown, however, how new neurons become functionally integrated into spatial circuits and contribute to hippocampus-mediated forms of learning and memory. To investigate these issues, we used a mouse model in which the differentiation of adult-generated dentate gyrus neurons can be anticipated by conditionally expressing the pro-differentiative gene PC3 (Tis21/BTG2 in nestin-positive progenitor cells. In contrast to previous studies that affected the number of newly generated neurons, this strategy selectively changes their timing of differentiation. New, adult-generated dentate gyrus progenitors, in which the PC3 transgene was expressed, showed accelerated differentiation and significantly reduced dendritic arborization and spine density. Functionally, this genetic manipulation specifically affected different hippocampus-dependent learning and memory tasks, including contextual fear conditioning, and selectively reduced synaptic plasticity in the dentate gyrus. Morphological and functional analyses of hippocampal neurons at different stages of differentiation, following transgene activation within defined time-windows, revealed that the new, adult-generated neurons up to 3-4 weeks of age are required not only to acquire new spatial information but also to use previously consolidated memories. Thus, the correct unwinding of these key memory functions, which can be an expression of the ability of adult-generated neurons to link subsequent events in memory circuits, is critically dependent on the correct timing of the initial stages of neuron maturation and connection to existing circuits.

Cancer stem cells and differentiation therapy.

Science.gov (United States)

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

Cancer stem cells can generate tumors from only a small number of cells, whereas differentiated cancer cells cannot. The prominent feature of cancer stem cells is its ability to self-renew and differentiate into multiple types of cancer cells. Cancer stem cells have several distinct tumorigenic abilities, including stem cell signal transduction, tumorigenicity, metastasis, and resistance to anticancer drugs, which are regulated by genetic or epigenetic changes. Like normal adult stem cells involved in various developmental processes and tissue homeostasis, cancer stem cells maintain their self-renewal capacity by activating multiple stem cell signaling pathways and inhibiting differentiation signaling pathways during cancer initiation and progression. Recently, many studies have focused on targeting cancer stem cells to eradicate malignancies by regulating stem cell signaling pathways, and products of some of these strategies are in preclinical and clinical trials. In this review, we describe the crucial features of cancer stem cells related to tumor relapse and drug resistance, as well as the new therapeutic strategy to target cancer stem cells named "differentiation therapy."

Differentiation of a bipotential glial progenitor cell in a single cell microculture.

Science.gov (United States)

Temple, S; Raff, M C

Although it is known that most cells of the vertebrate central nervous system (CNS) are derived from the neuroepithelial cells of the neural tube, the factors determining whether an individual neuroepithelial cell develops into a particular type of neurone or glial cell remain unknown. A promising model for studying this problem is the bipotential glial progenitor cell in the developing rat optic nerve; this cell differentiates into a particular type of astrocyte (a type-2 astrocyte) if cultured in 10% fetal calf serum (FCS) and into an oligodendrocyte if cultured in serum-free medium. As the oligodendrocyte-type-2 astrocyte (0-2A) progenitor cell can differentiate along either glial pathway in neurone-free cultures, living axons clearly are not required for its differentiation, at least in vitro. However, the studies on 0-2A progenitor cells were carried out in bulk cultures of optic nerve, and so it was possible that other cell-cell interactions were required for differentiation in culture. We show here that 0-2A progenitor cells can differentiate into type-2 astrocytes or oligodendrocytes when grown as isolated cells in microculture, indicating that differentiation along either glial pathway in vitro does not require signals from other CNS cells, apart from the signals provided by components of the culture medium. We also show that single 0-2A progenitor cells can differentiate along either pathway without dividing, supporting our previous studies using 3H-thymidine and suggesting that DNA replication is not required for these cells to choose between the two differentiation programmes.

Waveform relaxation methods for implicit differential equations

NARCIS (Netherlands)

P.J. van der Houwen; W.A. van der Veen

1996-01-01

textabstractWe apply a Runge-Kutta-based waveform relaxation method to initial-value problems for implicit differential equations. In the implementation of such methods, a sequence of nonlinear systems has to be solved iteratively in each step of the integration process. The size of these systems

Demystifying Differentiation for the Elementary Music Classroom

Science.gov (United States)

Hillier, Erin

2011-01-01

Many music educators struggle with adapting buildingwide professional development initiatives into their own curriculum and teaching practice while still maintaining the integrity of the musical experiences they bring to the classroom. One vastly popular trend in instructional strategies, differentiated instruction, is both accessible to the music…

Mesenchymal stem cell-like properties of CD133+ glioblastoma initiating cells

Science.gov (United States)

Pavon, Lorena Favaro; Sibov, Tatiana Tais; de Oliveira, Daniela Mara; Marti, Luciana C.; Cabral, Francisco Romero; de Souza, Jean Gabriel; Boufleur, Pamela; Malheiros, Suzana M.F.; de Paiva Neto, Manuel A.; da Cruz, Edgard Ferreira; Chudzinski-Tavassi, Ana Marisa; Cavalheiro, Sérgio

2016-01-01

Glioblastoma is composed of dividing tumor cells, stromal cells and tumor initiating CD133+ cells. Recent reports have discussed the origin of the glioblastoma CD133+ cells and their function in the tumor microenvironment. The present work sought to investigate the multipotent and mesenchymal properties of primary highly purified human CD133+ glioblastoma-initiating cells. To accomplish this aim, we used the following approaches: i) generation of tumor subspheres of CD133+ selected cells from primary cell cultures of glioblastoma; ii) analysis of the expression of pluripotency stem cell markers and mesenchymal stem cell (MSC) markers in the CD133+ glioblastoma-initiating cells; iii) side-by-side ultrastructural characterization of the CD133+ glioblastoma cells, MSC and CD133+ hematopoietic stem cells isolated from human umbilical cord blood (UCB); iv) assessment of adipogenic differentiation of CD133+ glioblastoma cells to test their MSC-like in vitro differentiation ability; and v) use of an orthotopic glioblastoma xenograft model in the absence of immune suppression. We found that the CD133+ glioblastoma cells expressed both the pluripotency stem cell markers (Nanog, Mush-1 and SSEA-3) and MSC markers. In addition, the CD133+ cells were able to differentiate into adipocyte-like cells. Transmission electron microscopy (TEM) demonstrated that the CD133+ glioblastoma-initiating cells had ultrastructural features similar to those of undifferentiated MSCs. In addition, when administered in vivo to non-immunocompromised animals, the CD133+ cells were also able to mimic the phenotype of the original patient's tumor. In summary, we showed that the CD133+ glioblastoma cells express molecular signatures of MSCs, neural stem cells and pluripotent stem cells, thus possibly enabling differentiation into both neural and mesodermal cell types. PMID:27244897

Clinical score to differentiate scrub typhus and dengue: A tool to differentiate scrub typhus and dengue

Directory of Open Access Journals (Sweden)

Shubhanker Mitra

2017-01-01

Full Text Available Background: Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. Materials and Methods: We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Results: Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%, total white blood cell count (7000 cells/cumm, hemoglobin (≤14 and >14 g/dL, total bilirubin (200 and ≥200 IU/dL, and altered sensorium (present or absent. Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval for model 2 was 0.84 (0.79–0.89. At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. Conclusion: In areas of high burden of ST and dengue, model 2 (the “clinical score to differentiate scrub typhus and dengue fever” is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Clinical Score to Differentiate Scrub Typhus and Dengue: A Tool to Differentiate Scrub Typhus and Dengue.

Science.gov (United States)

Mitra, Shubhanker; Gautam, Ira; Jambugulam, Mohan; Abhilash, Kundavaram Paul Prabhakar; Jayaseeelan, Vishalakshi

2017-01-01

Dengue and scrub typhus share similar clinical and epidemiological features, and are difficult to differentiate at initial presentation. Many places are endemic to both these infections where they comprise the majority of acute undifferentiated febrile illnesses. We aimed to develop a score that can differentiate scrub typhus from dengue. In this cross-sectional study, 188 cases of scrub typhus and 201 cases of dengue infection who presented to the emergency department or medicine outpatient clinic from September 2012 to April 2013 were included. Univariate followed by multivariate logistic regression analysis was performed to identify clinical features and laboratory results that were significantly different between the two groups. Each variable was assigned scores based on the strength of association and receiver operating characteristics area under the curve (ROC-AUC) was generated and compared. Six scoring models were explored to ascertain the model with the best fit. Model 2 was developed using the following six variables: oxygen saturation (>90%, ≤90%), total white blood cell count (7000 cells/cumm), hemoglobin (≤14 and >14 g/dL), total bilirubin (200 and ≥200 IU/dL), and altered sensorium (present or absent). Each variable was assigned scores based on its strength of association. The AUC-ROC curve (95% confidence interval) for model 2 was 0.84 (0.79-0.89). At the cut off score of 13, the sensitivity and specificity were 85% and 77% respectively, with a higher score favoring dengue. In areas of high burden of ST and dengue, model 2 (the "clinical score to differentiate scrub typhus and dengue fever") is a simple and rapid clinical scoring system that may be used to differentiate scrub typhus and dengue at initial presentation.

Automated work packages architecture: An initial set of human factors and instrumentation and controls requirements

Energy Technology Data Exchange (ETDEWEB)

Agarwal, Vivek [Idaho National Lab. (INL), Idaho Falls, ID (United States); Oxstrand, Johanna H. [Idaho National Lab. (INL), Idaho Falls, ID (United States); Le Blanc, Katya L. [Idaho National Lab. (INL), Idaho Falls, ID (United States)

2014-09-01

The work management process in current fleets of national nuclear power plants is so highly dependent on large technical staffs and quality of work instruction, i.e., paper-based, that this puts nuclear energy at somewhat of a long-term economic disadvantage and increase the possibility of human errors. Technologies like mobile portable devices and computer-based procedures can play a key role in improving the plant work management process, thereby increasing productivity and decreasing cost. Automated work packages are a fundamentally an enabling technology for improving worker productivity and human performance in nuclear power plants work activities because virtually every plant work activity is accomplished using some form of a work package. As part of this year’s research effort, automated work packages architecture is identified and an initial set of requirements identified, that are essential and necessary for implementation of automated work packages in nuclear power plants.

Analysis of integrated multiple 'omics' datasets reveals the mechanisms of initiation and determination in the formation of tuberous roots in Rehmannia glutinosa.

Science.gov (United States)

Li, Mingjie; Yang, Yanhui; Li, Xinyu; Gu, Li; Wang, Fengji; Feng, Fajie; Tian, Yunhe; Wang, Fengqing; Wang, Xiaoran; Lin, Wenxiong; Chen, Xinjian; Zhang, Zhongyi

2015-09-01

All tuberous roots in Rehmannia glutinosa originate from the expansion of fibrous roots (FRs), but not all FRs can successfully transform into tuberous roots. This study identified differentially expressed genes and proteins associated with the expansion of FRs, by comparing the tuberous root at expansion stages (initiated tuberous root, ITRs) and FRs at the seedling stage (initiated FRs, IFRs). The role of miRNAs in the expansion of FRs was also explored using the sRNA transcriptome and degradome to identify miRNAs and their target genes that were differentially expressed between ITRs and FRs at the mature stage (unexpanded FRs, UFRs, which are unable to expand into ITRs). A total of 6032 genes and 450 proteins were differentially expressed between ITRs and IFRs. Integrated analyses of these data revealed several genes and proteins involved in light signalling, hormone response, and signal transduction that might participate in the induction of tuberous root formation. Several genes related to cell division and cell wall metabolism were involved in initiating the expansion of IFRs. Of 135 miRNAs differentially expressed between ITRs and UFRs, there were 27 miRNAs whose targets were specifically identified in the degradome. Analysis of target genes showed that several miRNAs specifically expressed in UFRs were involved in the degradation of key genes required for the formation of tuberous roots. As far as could be ascertained, this is the first time that the miRNAs that control the transition of FRs to tuberous roots in R. glutinosa have been identified. This comprehensive analysis of 'omics' data sheds new light on the mechanisms involved in the regulation of tuberous roots formation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

PDASAC, Partial Differential Sensitivity Analysis of Stiff System

International Nuclear Information System (INIS)

Caracotsios, M.; Stewart, W.E.

2001-01-01

1 - Description of program or function: PDASAC solves stiff, nonlinear initial-boundary-value problems in a timelike dimension t and a space dimension x. Plane, circular cylindrical or spherical boundaries can be handled. Mixed-order systems of partial differential and algebraic equations can be analyzed with members of order or 0 or 1 in t, 0, 1 or 2 in x. Parametric sensitivities of the calculated states are computed simultaneously on request, via the Jacobian of the state equations. Initial and boundary conditions are efficiently reconciled. Local error control (in the max-norm or the 2-norm) is provided for the state vector and can include the parametric sensitivities if desired. 2 - Method of solution: The method of lines is used, with a user- selected x-grid and a minimum-bandwidth finite-difference approximations of the x-derivatives. Starting conditions are reconciled with a damped Newton algorithm adapted from Bain and Stewart (1991). Initial step selection is done by the first-order algorithms of Shampine (1987), extended here to differential- algebraic equation systems. The solution is continued with the DASSL predictor-corrector algorithm (Petzold 1983, Brenan et al. 1989) with the initial acceleration phase deleted and with row scaling of the Jacobian added. The predictor and corrector are expressed in divided-difference form, with the fixed-leading-coefficient form of corrector (Jackson and Sacks-Davis 1989; Brenan et al. 1989). Weights for the error tests are updated in each step with the user's tolerances at the predicted state. Sensitivity analysis is performed directly on the corrector equations of Caracotsios and Stewart (1985) and is extended here to the initialization when needed. 3 - Restrictions on the complexity of the problem: This algorithm, like DASSL, performs well on differential-algebraic equation systems of index 0 and 1 but not on higher-index systems; see Brenan et al. (1989). The user assigned the work array lengths and the output

General conditions guaranteeing the solvability of the Cauchy problem for functional differential equations

Czech Academy of Sciences Publication Activity Database

Dilna, N.; Rontó, András

2008-01-01

Roč. 133, č. 4 (2008), s. 435-445 ISSN 0862-7959 R&D Projects: GA ČR(CZ) GA201/06/0254 Institutional research plan: CEZ:AV0Z10190503 Keywords : functional differential equation * Cauchy problem * initial value problem * differential inequality Subject RIV: BA - General Mathematics

CFORM- LINEAR CONTROL SYSTEM DESIGN AND ANALYSIS: CLOSED FORM SOLUTION AND TRANSIENT RESPONSE OF THE LINEAR DIFFERENTIAL EQUATION

Science.gov (United States)

Jamison, J. W.

1994-01-01

CFORM was developed by the Kennedy Space Center Robotics Lab to assist in linear control system design and analysis using closed form and transient response mechanisms. The program computes the closed form solution and transient response of a linear (constant coefficient) differential equation. CFORM allows a choice of three input functions: the Unit Step (a unit change in displacement); the Ramp function (step velocity); and the Parabolic function (step acceleration). It is only accurate in cases where the differential equation has distinct roots, and does not handle the case for roots at the origin (s=0). Initial conditions must be zero. Differential equations may be input to CFORM in two forms - polynomial and product of factors. In some linear control analyses, it may be more appropriate to use a related program, Linear Control System Design and Analysis (KSC-11376), which uses root locus and frequency response methods. CFORM was written in VAX FORTRAN for a VAX 11/780 under VAX VMS 4.7. It has a central memory requirement of 30K. CFORM was developed in 1987.

Decreased Intracellular pH Induced by Cariporide Differentially Contributes to Human Umbilical Cord-Derived Mesenchymal Stem Cells Differentiation

Directory of Open Access Journals (Sweden)

Wei Gao

2014-01-01

Full Text Available Background/Aims: Na+/H+ exchanger 1 (NHE1 is an important regulator of intracellular pH (pHi. High pHi is required for cell proliferation and differentiation. Our previous study has proven that the pHi of mesenchymal stem cells is higher than that of normal differentiated cells and similar to tumor cells. NHE1 is highly expressed in both mesenchymal stem cells and tumor cells. Targeted inhibition of NHE1 could induce differentiation of K562 leukemia cells. In the present paper we explored whether inhibition of NHE1 could induce differentiation of mesenchymal stem cells. Methods: MSCs were obtained from human umbilical cord and both the surface phenotype and functional characteristics were analyzed. Selective NHE1 inhibitor cariporide was used to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs. The pHi and the differentiation of hUC-MSCs were compared upon cariporide treatment. The putative signaling pathway involved was also explored. Results: The pHi of hUC-MSCs was decreased upon cariporide treatment. Cariporide up-regulated the osteogenic differentiation of hUC-MSCs while the adipogenic differentiation was not affected. For osteogenic differentiation, β-catenin expression was up-regulated upon cariporide treatment. Conclusion: Decreased pHi induced by cariporide differentially contributes to hUC-MSCs differentiation.

Optimal stability polynomials for numerical integration of initial value problems

KAUST Repository

Ketcheson, David I.; Ahmadia, Aron

2013-01-01

We consider the problem of finding optimally stable polynomial approximations to the exponential for application to one-step integration of initial value ordinary and partial differential equations. The objective is to find the largest stable step

CD73 Regulates Stemness and Epithelial-Mesenchymal Transition in Ovarian Cancer-Initiating Cells

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Michela Lupia

2018-04-01

Full Text Available Summary: Cancer-initiating cells (CICs have been implicated in tumor development and aggressiveness. In ovarian carcinoma (OC, CICs drive tumor formation, dissemination, and recurrence, as well as drug resistance, thus accounting for the high death-to-incidence ratio of this neoplasm. However, the molecular mechanisms that underlie such a pathogenic role of ovarian CICs (OCICs remain elusive. Here, we have capitalized on primary cells either from OC or from its tissues of origin to obtain the transcriptomic profile associated with OCICs. Among the genes differentially expressed in OCICs, we focused on CD73, which encodes the membrane-associated 5′-ectonucleotidase. The genetic inactivation of CD73 in OC cells revealed that this molecule is causally involved in sphere formation and tumor initiation, thus emerging as a driver of OCIC function. Furthermore, functional inhibition of CD73 via either a chemical compound or a neutralizing antibody reduced sphere formation and tumorigenesis, highlighting the druggability of CD73 in the context of OCIC-directed therapies. The biological function of CD73 in OCICs required its enzymatic activity and involved adenosine signaling. Mechanistically, CD73 promotes the expression of stemness and epithelial-mesenchymal transition-associated genes, implying a regulation of OCIC function at the transcriptional level. CD73, therefore, is involved in OCIC biology and may represent a therapeutic target for innovative treatments aimed at OC eradication. : Cavallaro et al. characterized the transcriptome of OCIC-enriched primary cultures and found CD73 as an upregulated gene. CD73 was then shown to regulate the expression of stemness and EMT-associated genes. The expression and function of CD73 in OCICs is required for tumor initiation, and CD73-targeted drugs decrease the rate of tumor take and inhibit cancer growth. Keywords: CD73, ovarian cancer, cancer-initiating cells, cancer stem cells, EMT, adenosine

Influence of substrate composition on human embryonic stem cell differentiation and extracellular matrix production in embryoid bodies.

Science.gov (United States)

Laperle, Alex; Masters, Kristyn S; Palecek, Sean P

2015-01-01

Stem cells reside in specialized niches in vivo. Specific factors, including the extracellular matrix (ECM), in these niches are directly responsible for maintaining the stem cell population. During development, components of the stem cell microenvironment also control differentiation with precise spatial and temporal organization. The stem cell microenvironment is dynamically regulated by the cellular component, including stem cells themselves. Thus, a mechanism exists whereby stem cells modify the ECM, which in turn affects the fate of the stem cell. In this study, we investigated whether the type of ECM initially adsorbed to the culture substrate can influence the composition of the ECM deposited by human embryonic stem cells (hESCs) differentiating in embryoid bodies, and whether different ECM composition and deposition profiles elicit distinct differentiation fates. We have shown that the initial ECM environment hESCs are exposed to affects the fate decisions of those cells and that this initial ECM environment is constantly modified during the differentiation process. © 2014 American Institute of Chemical Engineers.

Skeletal myocyte hypertrophy requires mTOR kinase activity and S6K1

International Nuclear Information System (INIS)

Park, In-Hyun; Erbay, Ebru; Nuzzi, Paul; Chen Jie

2005-01-01

The protein kinase mammalian target of rapamycin (mTOR) is a central regulator of cell proliferation and growth, with the ribosomal subunit S6 kinase 1 (S6K1) as one of the key downstream signaling effectors. A critical role of mTOR signaling in skeletal muscle differentiation has been identified recently, and an unusual regulatory mechanism independent of mTOR kinase activity and S6K1 is revealed. An mTOR pathway has also been reported to regulate skeletal muscle hypertrophy, but the regulatory mechanism is not completely understood. Here, we report the investigation of mTOR's function in insulin growth factor I (IGF-I)-induced C2C12 myotube hypertrophy. Added at a later stage when rapamycin no longer had any effect on normal myocyte differentiation, rapamycin completely blocked myocyte hypertrophy as measured by myotube diameter. Importantly, a concerted increase of average myonuclei per myotube was observed in IGF-I-stimulated myotubes, which was also inhibited by rapamycin added at a time when it no longer affected normal differentiation. The mTOR protein level, its catalytic activity, its phosphorylation on Ser2448, and the activity of S6K1 were all found increased in IGF-I-stimulated myotubes compared to unstimulated myotubes. Using C2C12 cells stably expressing rapamycin-resistant forms of mTOR and S6K1, we provide genetic evidence for the requirement of mTOR and its downstream effector S6K1 in the regulation of myotube hypertrophy. Our results suggest distinct mTOR signaling mechanisms in different stages of skeletal muscle development: While mTOR regulates the initial myoblast differentiation in a kinase-independent and S6K1-independent manner, the hypertrophic function of mTOR requires its kinase activity and employs S6K1 as a downstream effector

Dosimetry-guided high-activity 131I therapy in patients with advanced differentiated thyroid carcinoma: initial experience

International Nuclear Information System (INIS)

Verburg, Frederik A.; Haenscheid, Heribert; Biko, Johannes; Hategan, Maria C.; Lassmann, Michael; Kreissl, Michael C.; Reiners, Christoph; Luster, Markus

2010-01-01

In patients with advanced differentiated thyroid carcinoma (DTC), therapy with the highest safe 131 I activity is desirable to maximize the tumour radiation dose yet avoid severe myelotoxicity. Recently, the European Association of Nuclear Medicine (EANM) published a standard operational procedure (SOP) for pre-therapeutic dosimetry in DTC patients incorporating a safety threshold of a 2 Gy absorbed dose to the blood as a surrogate for the red marrow. We sought to evaluate the safety and effectiveness in everyday tertiary referral centre practice of treating advanced DTC with high 131 I activities chosen primarily based on the results of dosimetry following this SOP. We retrospectively assessed toxicity as well as biochemical and scintigraphic response in our first ten patients receiving such therapy for advanced DTC. The 10 patients received a total of 13 dosimetrically guided treatments with a median administered activity of 14.0 GBq (range: 7.0-21.4 GBq) 131 I. After 6 of 13 treatments in 6 of 10 patients, short-term side effects of 131 I therapy, namely nausea, vomiting or sialadenitis, were observed. Leukocyte and platelet counts dropped significantly in the weeks after 131 I treatment, but returned to pre-treatment levels by 3 months post-therapy. Serum thyroglobulin levels decreased after 12 of 13 treatments (median reduction: 58%) in 9 of 10 patients. In our initial patient cohort, high-activity 131 I therapy for advanced DTC based on pre-therapeutic blood dosimetry following the EANM SOP was safe and well tolerated. Such treatment almost always produced a partial biochemical tumour response. (orig.)

Sexual differentiation in three unconventional mammals: spotted hyenas, elephants and tammar wallabies.

Science.gov (United States)

Glickman, Stephen E; Short, Roger V; Renfree, Marilyn B

2005-11-01

The present review explores sexual differentiation in three non-conventional species: the spotted hyena, the elephant and the tammar wallaby, selected because of the natural challenges they present for contemporary understanding of sexual differentiation. According to the prevailing view of mammalian sexual differentiation, originally proposed by Alfred Jost, secretion of androgen and anti-Mullerian hormone (AMH) by the fetal testes during critical stages of development accounts for the full range of sexually dimorphic urogenital traits observed at birth. Jost's concept was subsequently expanded to encompass sexual differentiation of the brain and behavior. Although the central focus of this review involves urogenital development, we assume that the novel mechanisms described in this article have potentially significant implications for sexual differentiation of brain and behavior, a transposition with precedent in the history of this field. Contrary to the "specific" requirements of Jost's formulation, female spotted hyenas and elephants initially develop male-type external genitalia prior to gonadal differentiation. In addition, the administration of anti-androgens to pregnant female spotted hyenas does not prevent the formation of a scrotum, pseudoscrotum, penis or penile clitoris in the offspring of treated females, although it is not yet clear whether the creation of masculine genitalia involves other steroids or whether there is a genetic mechanism bypassing a hormonal mediator. Wallabies, where sexual differentiation occurs in the pouch after birth, provide the most conclusive evidence for direct genetic control of sexual dimorphism, with the scrotum developing only in males and the pouch and mammary glands only in females, before differentiation of the gonads. The development of the pouch and mammary gland in females and the scrotum in males is controlled by genes on the X chromosome. In keeping with the "expanded" version of Jost's formulation, secretion

FORSIM-6, Automatic Solution of Coupled Differential Equation System

International Nuclear Information System (INIS)

Carver, M.B.; Stewart, D.G.; Blair, J.M.; Selander, W.N.

1983-01-01

1 - Description of problem or function: The FORSIM program is a versatile package which automates the solution of coupled differential equation systems. The independent variables are time, and up to three space coordinates, and the equations may be any mixture of partial and/or ordinary differential equations. The philosophy of the program is to provide a tool which will solve a system of differential equations for a user who has basic but unspecialized knowledge of numerical analysis and FORTRAN. The equations to be solved, together with the initial conditions and any special instructions, may be specified by the user in a single FORTRAN subroutine, although he may write a number of routines if this is more suitable. These are then loaded with the control routines, which perform the solution and any requested input and output. 2 - Method of solution: Partial differential equations are automatically converted into sets of coupled ordinary differential equations by variable order discretization in the spatial dimensions. These and other ordinary differential equations are integrated continuously in time using efficient variable order, variable step, error-controlled algorithms

Pricing strategies and service differentiation

NARCIS (Netherlands)

Mandjes, M.R.H.

2004-01-01

This paper analyzes a communication network, used by customers with heterogeneous service requirements. We investigate priority queueing as a way to establish service differentiation. It is assumed that there is an infinite population of customers, who join the network as long as their utility

XMDS2: Fast, scalable simulation of coupled stochastic partial differential equations

Science.gov (United States)

Dennis, Graham R.; Hope, Joseph J.; Johnsson, Mattias T.

2013-01-01

XMDS2 is a cross-platform, GPL-licensed, open source package for numerically integrating initial value problems that range from a single ordinary differential equation up to systems of coupled stochastic partial differential equations. The equations are described in a high-level XML-based script, and the package generates low-level optionally parallelised C++ code for the efficient solution of those equations. It combines the advantages of high-level simulations, namely fast and low-error development, with the speed, portability and scalability of hand-written code. XMDS2 is a complete redesign of the XMDS package, and features support for a much wider problem space while also producing faster code. Program summaryProgram title: XMDS2 Catalogue identifier: AENK_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENK_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: GNU General Public License, version 2 No. of lines in distributed program, including test data, etc.: 872490 No. of bytes in distributed program, including test data, etc.: 45522370 Distribution format: tar.gz Programming language: Python and C++. Computer: Any computer with a Unix-like system, a C++ compiler and Python. Operating system: Any Unix-like system; developed under Mac OS X and GNU/Linux. RAM: Problem dependent (roughly 50 bytes per grid point) Classification: 4.3, 6.5. External routines: The external libraries required are problem-dependent. Uses FFTW3 Fourier transforms (used only for FFT-based spectral methods), dSFMT random number generation (used only for stochastic problems), MPI message-passing interface (used only for distributed problems), HDF5, GNU Scientific Library (used only for Bessel-based spectral methods) and a BLAS implementation (used only for non-FFT-based spectral methods). Nature of problem: General coupled initial-value stochastic partial differential equations. Solution method: Spectral method

So much to do, so little time. To accomplish the mandatory initiatives of ARRA, healthcare organizations will require significant and thoughtful planning, prioritization and execution.

Science.gov (United States)

Klein, Kimberly

2010-01-01

The American Recovery and Reinvestment Act of 2009 (ARRA) has set forth legislation for the healthcare community to achieve adoption of electronic health records (EHR), as well as form data standards, health information exchanges (HIE) and compliance with more stringent security and privacy controls under the HITECH Act. While the Office of the National Coordinator for Health Information Technology (ONCHIT) works on the definition of both "meaningful use" and "certification" of information technology systems, providers in particular must move forward with their IT initiatives to achieve the basic requirements for Medicare and Medicaid incentives starting in 2011, and avoid penalties that will reduce reimbursement beginning in 2015. In addition, providers, payors, government and non-government stakeholders will all have to balance the implementation of EHRs, working with HIEs, at the same time that they must upgrade their systems to be in compliance with ICD-10 and HIPAA 5010 code sets. Compliance deadlines for EHRs and HIEs begin in 2011, while ICD-10 diagnosis and procedure code sets compliance is required by October 2013 and HIPAA 5010 transaction sets, with one exception, is required by January 1, 2012. In order to accomplish these strategic and mandatory initiatives successfully and simultaneously, healthcare organizations will require significant and thoughtful planning, prioritization and execution.

Photon Differential Splatting for Rendering Caustics

DEFF Research Database (Denmark)

Frisvad, Jeppe Revall; Schjøth, Lars; Erleben, Kenny

2014-01-01

We present a photon splatting technique which reduces noise and blur in the rendering of caustics. Blurring of illumination edges is an inherent problem in photon splatting, as each photon is unaware of its neighbours when being splatted. This means that the splat size is usually based...... on heuristics rather than knowledge of the local flux density. We use photon differentials to determine the size and shape of the splats such that we achieve adaptive anisotropic flux density estimation in photon splatting. As compared to previous work that uses photon differentials, we present the first method...... where no photons or beams or differentials need to be stored in a map. We also present improvements in the theory of photon differentials, which give more accurate results and a faster implementation. Our technique has good potential for GPU acceleration, and we limit the number of parameters requiring...

National Maglev initiative: California line electric utility power system requirements

Science.gov (United States)

Save, Phil

1994-01-01

The electrical utility power system requirements were determined for a Maglev line from San Diego to San Francisco and Sacramento with a maximum capacity of 12,000 passengers an hour in each direction at a speed of 300 miles per hour, or one train every 30 seconds in each direction. Basically the Maglev line requires one 50-MVA substation every 12.5 miles. The need for new power lines to serve these substations and their voltage levels are based not only on equipment loading criteria but also on limitations due to voltage flicker and harmonics created by the Maglev system. The resulting power system requirements and their costs depend mostly on the geographical area, urban or suburban with 'strong' power systems, or mountains and rural areas with 'weak' power systems. A reliability evaluation indicated that emergency power sources, such as a 10-MW battery at each substation, were not justified if sufficient redundancy is provided in the design of the substations and the power lines serving them. With a cost of $5.6 M per mile, the power system requirements, including the 12-kV DC cables and the inverters along the Maglev line, were found to be the second largest cost component of the Maglev system, after the cost of the guideway system ($9.1 M per mile), out of a total cost of $23 M per mile.

TIP48/Reptin and H2A.Z requirement for initiating chromatin remodeling in estrogen-activated transcription.

Directory of Open Access Journals (Sweden)

Mathieu Dalvai

2013-04-01

Full Text Available Histone variants, including histone H2A.Z, are incorporated into specific genomic sites and participate in transcription regulation. The role of H2A.Z at these sites remains poorly characterized. Our study investigates changes in the chromatin environment at the Cyclin D1 gene (CCND1 during transcriptional initiation in response to estradiol in estrogen receptor positive mammary tumour cells. We show that H2A.Z is present at the transcription start-site and downstream enhancer sequences of CCND1 when the gene is poorly transcribed. Stimulation of CCND1 expression required release of H2A.Z concomitantly from both these DNA elements. The AAA+ family members TIP48/reptin and the histone variant H2A.Z are required to remodel the chromatin environment at CCND1 as a prerequisite for binding of the estrogen receptor (ERα in the presence of hormone. TIP48 promotes acetylation and exchange of H2A.Z, which triggers a dissociation of the CCND1 3' enhancer from the promoter, thereby releasing a repressive intragenic loop. This release then enables the estrogen receptor to bind to the CCND1 promoter. Our findings provide new insight into the priming of chromatin required for transcription factor access to their target sequence. Dynamic release of gene loops could be a rapid means to remodel chromatin and to stimulate transcription in response to hormones.

Numerical methods for differential equations and applications

International Nuclear Information System (INIS)

Ixaru, L.G.

1984-01-01

This book is addressed to persons who, without being professionals in applied mathematics, are often faced with the problem of numerically solving differential equations. In each of the first three chapters a definite class of methods is discussed for the solution of the initial value problem for ordinary differential equations: multistep methods; one-step methods; and piecewise perturbation methods. The fourth chapter is mainly focussed on the boundary value problems for linear second-order equations, with a section devoted to the Schroedinger equation. In the fifth chapter the eigenvalue problem for the radial Schroedinger equation is solved in several ways, with computer programs included. (Auth.)

Only one ATP-binding DnaX subunit is required for initiation complex formation by the Escherichia coli DNA polymerase III holoenzyme.

Science.gov (United States)

Wieczorek, Anna; Downey, Christopher D; Dallmann, H Garry; McHenry, Charles S

2010-09-17

The DnaX complex (DnaX(3)δδ'χ psi) within the Escherichia coli DNA polymerase III holoenzyme serves to load the dimeric sliding clamp processivity factor, β(2), onto DNA. The complex contains three DnaX subunits, which occur in two forms: τ and the shorter γ, produced by translational frameshifting. Ten forms of E. coli DnaX complex containing all possible combinations of wild-type or a Walker A motif K51E variant τ or γ have been reconstituted and rigorously purified. DnaX complexes containing three DnaX K51E subunits do not bind ATP. Comparison of their ability to support formation of initiation complexes, as measured by processive replication by the DNA polymerase III holoenzyme, indicates a minimal requirement for one ATP-binding DnaX subunit. DnaX complexes containing two mutant DnaX subunits support DNA synthesis at about two-thirds the level of their wild-type counterparts. β(2) binding (determined functionally) is diminished 12-30-fold for DnaX complexes containing two K51E subunits, suggesting that multiple ATPs must be bound to place the DnaX complex into a conformation with maximal affinity for β(2). DNA synthesis activity can be restored by increased concentrations of β(2). In contrast, severe defects in ATP hydrolysis are observed upon introduction of a single K51E DnaX subunit. Thus, ATP binding, hydrolysis, and the ability to form initiation complexes are not tightly coupled. These results suggest that although ATP hydrolysis likely enhances β(2) loading, it is not absolutely required in a mechanistic sense for formation of functional initiation complexes.

Automatic differentiation tools in the dynamic simulation of chemical engineering processes

Directory of Open Access Journals (Sweden)

Castro M.C.

2000-01-01

Full Text Available Automatic Differentiation is a relatively recent technique developed for the differentiation of functions applicable directly to the source code to compute the function written in standard programming languages. That technique permits the automatization of the differentiation step, crucial for dynamic simulation and optimization of processes. The values for the derivatives obtained with AD are exact (to roundoff. The theoretical exactness of the AD comes from the fact that it uses the same rules of differentiation as in differential calculus, but these rules are applied to an algorithmic specification of the function rather than to a formula. The main purpose of this contribution is to discuss the impact of Automatic Differentiation in the field of dynamic simulation of chemical engineering processes. The influence of the differentiation technique on the behavior of the integration code, the performance of the generated code and the incorporation of AD tools in consistent initialization tools are discussed from the viewpoint of dynamic simulation of typical models in chemical engineering.

Application of Legendre spectral-collocation method to delay differential and stochastic delay differential equation

Science.gov (United States)

Khan, Sami Ullah; Ali, Ishtiaq

2018-03-01

Explicit solutions to delay differential equation (DDE) and stochastic delay differential equation (SDDE) can rarely be obtained, therefore numerical methods are adopted to solve these DDE and SDDE. While on the other hand due to unstable nature of both DDE and SDDE numerical solutions are also not straight forward and required more attention. In this study, we derive an efficient numerical scheme for DDE and SDDE based on Legendre spectral-collocation method, which proved to be numerical methods that can significantly speed up the computation. The method transforms the given differential equation into a matrix equation by means of Legendre collocation points which correspond to a system of algebraic equations with unknown Legendre coefficients. The efficiency of the proposed method is confirmed by some numerical examples. We found that our numerical technique has a very good agreement with other methods with less computational effort.

Proteomic analysis of cAMP-mediated signaling during differentiation of 3 T3-L1 preadipocytes

DEFF Research Database (Denmark)

Borkowski, Kamil; Wrzesinski, Krzysztow; Rogowska-Wrzesinska, Adelina

2014-01-01

Initiation of adipocyte differentiation is promoted by the synergistic action of insulin/insulin-like growth factor, glucocorticoids, and agents activating cAMP-dependent signaling. The action of cAMP is mediated via PKA and Epac, where at least part of the PKA function relates to strong repression...... a comprehensive evaluation of Epac-mediated processes and their interplay with PKA during the initiation of 3 T3-L1 preadipocyte differentiation using a combination of proteomics, molecular approaches, and bioinformatics. Proteomic analyses revealed 7 proteins specifically regulated in response to Epac activation......-dependent signaling thereby adding a novel facet to our understanding of cAMP-mediated potentiation of adipocyte differentiation....

Endogenous anticancer mechanism: differentiation.

Science.gov (United States)

Werneck, Miriam Bianchi de Frontin

2012-06-01

It has been recently shown that within heterogeneous tumor masses a small population of less differentiated transformed cells has the ability to self-renew and regenerate the bulk of the tumor. Their similarities with normal stem cells in terms of gene expression patterns, proliferative capacity and surface markers rendered them the name of cancer stem-like cells (CSC), and these are thought to be the tumor initiating cells (TIC). Their limited susceptibility to classical anti-tumor therapy help explain the high incidence of cancer-treatment relapses observed in selected malignancies. Much effort is being directed towards the understanding of factors that maintain CSC survival and their self-renewal capacity, with the goal that these same signaling pathways can be harnessed for treatments that aim at inducing CSC differentiation. This review will discuss the CSC theory, its implications, potential signaling pathways responsible for maintaining their undifferentiated and pluripotent states, and new venues being explored to target these cells in modern cancer therapy.

Biomass pyrolysis and combustion integral and differential reaction heats with temperatures using thermogravimetric analysis/differential scanning calorimetry.

Science.gov (United States)

Shen, Jiacheng; Igathinathane, C; Yu, Manlu; Pothula, Anand Kumar

2015-06-01

Integral reaction heats of switchgrass, big bluestem, and corn stalks were determined using thermogravimetric analysis/differential scanning calorimetry (TGA/DSC). Iso-conversion differential reaction heats using TGA/DSC pyrolysis and combustion of biomass were not available, despite reports available on heats required and released. A concept of iso-conversion differential reaction heats was used to determine the differential reaction heats of each thermal characteristics segment of these materials. Results showed that the integral reaction heats were endothermic from 30 to 700°C for pyrolysis of switchgrass and big bluestem, but they were exothermic for corn stalks prior to 587°C. However, the integral reaction heats for combustion of the materials followed an endothermic to exothermic transition. The differential reaction heats of switchgrass pyrolysis were predominantly endothermic in the fraction of mass loss (0.0536-0.975), and were exothermic for corn stalks (0.0885-0.850) and big bluestem (0.736-0.919). Study results provided better insight into biomass thermal mechanism. Published by Elsevier Ltd.

Complete motif analysis of sequence requirements for translation initiation at non-AUG start codons.

Science.gov (United States)

Diaz de Arce, Alexander J; Noderer, William L; Wang, Clifford L

2018-01-25

The initiation of mRNA translation from start codons other than AUG was previously believed to be rare and of relatively low impact. More recently, evidence has suggested that as much as half of all translation initiation utilizes non-AUG start codons, codons that deviate from AUG by a single base. Furthermore, non-AUG start codons have been shown to be involved in regulation of expression and disease etiology. Yet the ability to gauge expression based on the sequence of a translation initiation site (start codon and its flanking bases) has been limited. Here we have performed a comprehensive analysis of translation initiation sites that utilize non-AUG start codons. By combining genetic-reporter, cell-sorting, and high-throughput sequencing technologies, we have analyzed the expression associated with all possible variants of the -4 to +4 positions of non-AUG translation initiation site motifs. This complete motif analysis revealed that 1) with the right sequence context, certain non-AUG start codons can generate expression comparable to that of AUG start codons, 2) sequence context affects each non-AUG start codon differently, and 3) initiation at non-AUG start codons is highly sensitive to changes in the flanking sequences. Complete motif analysis has the potential to be a key tool for experimental and diagnostic genomics. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Numerov iteration method for second order integral-differential equation

International Nuclear Information System (INIS)

Zeng Fanan; Zhang Jiaju; Zhao Xuan

1987-01-01

In this paper, Numerov iterative method for second order integral-differential equation and system of equations are constructed. Numerical examples show that this method is better than direct method (Gauss elimination method) in CPU time and memoy requireing. Therefore, this method is an efficient method for solving integral-differential equation in nuclear physics

Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

Science.gov (United States)

Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

2017-05-01

Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

Mobile computing initiatives within pharmacy education.

Science.gov (United States)

Cain, Jeff; Bird, Eleanora R; Jones, Mikael

2008-08-15

To identify mobile computing initiatives within pharmacy education, including how devices are obtained, supported, and utilized within the curriculum. An 18-item questionnaire was developed and delivered to academic affairs deans (or closest equivalent) of 98 colleges and schools of pharmacy. Fifty-four colleges and schools completed the questionnaire for a 55% completion rate. Thirteen of those schools have implemented mobile computing requirements for students. Twenty schools reported they were likely to formally consider implementing a mobile computing initiative within 5 years. Numerous models of mobile computing initiatives exist in terms of device obtainment, technical support, infrastructure, and utilization within the curriculum. Responders identified flexibility in teaching and learning as the most positive aspect of the initiatives and computer-aided distraction as the most negative, Numerous factors should be taken into consideration when deciding if and how a mobile computing requirement should be implemented.

SLA-aware differentiated QoS in elastic optical networks

Science.gov (United States)

Agrawal, Anuj; Vyas, Upama; Bhatia, Vimal; Prakash, Shashi

2017-07-01

The quality of service (QoS) offered by optical networks can be improved by accurate provisioning of service level specifications (SLSs) included in the service level agreement (SLA). A large number of users coexisting in the network require different services. Thus, a pragmatic network needs to offer a differentiated QoS to a variety of users according to the SLA contracted for different services at varying costs. In conventional wavelength division multiplexed (WDM) optical networks, service differentiation is feasible only for a limited number of users because of its fixed-grid structure. Newly introduced flex-grid based elastic optical networks (EONs) are more adaptive to traffic requirements as compared to the WDM networks because of the flexibility in their grid structure. Thus, we propose an efficient SLA provisioning algorithm with improved QoS for these flex-grid EONs empowered by optical orthogonal frequency division multiplexing (O-OFDM). The proposed algorithm, called SLA-aware differentiated QoS (SADQ), employs differentiation at the level of routing, spectrum allocation, and connection survivability. The proposed SADQ aims to accurately provision the SLA using such multilevel differentiation with an objective to improve the spectrum utilization from the network operator's perspective. SADQ is evaluated for three different CoSs under various traffic demand patterns and for different ratios of the number of requests belonging to the three considered CoSs. We propose two new SLA metrics for the improvement of functional QoS requirements, namely, security, confidentiality and survivability of high class of service (CoS) traffic. Since, to the best of our knowledge, the proposed SADQ is the first scheme in optical networks to employ exhaustive differentiation at the levels of routing, spectrum allocation, and survivability in a single algorithm, we first compare the performance of SADQ in EON and currently deployed WDM networks to assess the

Singular Cauchy Initial Value Problem for Certain Classes of Integro-Differential Equations

Directory of Open Access Journals (Sweden)

Šmarda Zdeněk

2010-01-01

Full Text Available The existence and uniqueness of solutions and asymptotic estimate of solution formulas are studied for the following initial value problem: , , , where is a constant and . An approach which combines topological method of T. Ważewski and Schauder's fixed point theorem is used.

A Gompertz population model with Allee effect and fuzzy initial values

Science.gov (United States)

Amarti, Zenia; Nurkholipah, Nenden Siti; Anggriani, Nursanti; Supriatna, Asep K.

2018-03-01

Growth and population dynamics models are important tools used in preparing a good management for society to predict the future of population or species. This has been done by various known methods, one among them is by developing a mathematical model that describes population growth. Models are usually formed into differential equations or systems of differential equations, depending on the complexity of the underlying properties of the population. One example of biological complexity is Allee effect. It is a phenomenon showing a high correlation between very small population size and the mean individual fitness of the population. In this paper the population growth model used is the Gompertz equation model by considering the Allee effect on the population. We explore the properties of the solution to the model numerically using the Runge-Kutta method. Further exploration is done via fuzzy theoretical approach to accommodate uncertainty of the initial values of the model. It is known that an initial value greater than the Allee threshold will cause the solution rises towards carrying capacity asymptotically. However, an initial value smaller than the Allee threshold will cause the solution decreases towards zero asymptotically, which means the population is eventually extinct. Numerical solutions show that modeling uncertain initial value of the critical point A (the Allee threshold) with a crisp initial value could cause the extinction of population of a certain possibilistic degree, depending on the predetermined membership function of the initial value.

Temporal expression pattern of genes during the period of sex differentiation in human embryonic gonads

DEFF Research Database (Denmark)

Mamsen, Linn S; Ernst, Emil H; Borup, Rehannah

2017-01-01

The precise timing and sequence of changes in expression of key genes and proteins during human sex-differentiation and onset of steroidogenesis was evaluated by whole-genome expression in 67 first trimester human embryonic and fetal ovaries and testis and confirmed by qPCR and immunohistochemistry...... (IHC). SRY/SOX9 expression initiated in testis around day 40 pc, followed by initiation of AMH and steroidogenic genes required for androgen production at day 53 pc. In ovaries, gene expression of RSPO1, LIN28, FOXL2, WNT2B, and ETV5, were significantly higher than in testis, whereas GLI1...... was significantly higher in testis than ovaries. Gene expression was confirmed by IHC for GAGE, SOX9, AMH, CYP17A1, LIN28, WNT2B, ETV5 and GLI1. Gene expression was not associated with the maternal smoking habits. Collectively, a precise temporal determination of changes in expression of key genes involved in human...

Diversity in TAF proteomics: consequences for cellular differentiation and migration.

Science.gov (United States)

Kazantseva, Jekaterina; Palm, Kaia

2014-09-19

Development is a highly controlled process of cell proliferation and differentiation driven by mechanisms of dynamic gene regulation. Specific DNA binding factors for establishing cell- and tissue-specific transcriptional programs have been characterised in different cell and animal models. However, much less is known about the role of "core transcription machinery" during cell differentiation, given that general transcription factors and their spatiotemporally patterned activity govern different aspects of cell function. In this review, we focus on the role of TATA-box associated factor 4 (TAF4) and its functional isoforms generated by alternative splicing in controlling lineage-specific differentiation of normal mesenchymal stem cells and cancer stem cells. In the light of our recent findings, induction, control and maintenance of cell differentiation status implies diversification of the transcription initiation apparatus orchestrated by alternative splicing.

Differential topology

CERN Document Server

Guillemin, Victor

2010-01-01

Differential Topology provides an elementary and intuitive introduction to the study of smooth manifolds. In the years since its first publication, Guillemin and Pollack's book has become a standard text on the subject. It is a jewel of mathematical exposition, judiciously picking exactly the right mixture of detail and generality to display the richness within. The text is mostly self-contained, requiring only undergraduate analysis and linear algebra. By relying on a unifying idea-transversality-the authors are able to avoid the use of big machinery or ad hoc techniques to establish the main

FIDEA: a server for the functional interpretation of differential expression analysis.

KAUST Repository

D'Andrea, Daniel; Grassi, Luigi; Mazzapioda, Mariagiovanna; Tramontano, Anna

2013-01-01

The results of differential expression analyses provide scientists with hundreds to thousands of differentially expressed genes that need to be interpreted in light of the biology of the specific system under study. This requires mapping the genes

Solutions to an advanced functional partial differential equation of the pantograph type.

Science.gov (United States)

Zaidi, Ali A; Van Brunt, B; Wake, G C

2015-07-08

A model for cells structured by size undergoing growth and division leads to an initial boundary value problem that involves a first-order linear partial differential equation with a functional term. Here, size can be interpreted as DNA content or mass. It has been observed experimentally and shown analytically that solutions for arbitrary initial cell distributions are asymptotic as time goes to infinity to a certain solution called the steady size distribution. The full solution to the problem for arbitrary initial distributions, however, is elusive owing to the presence of the functional term and the paucity of solution techniques for such problems. In this paper, we derive a solution to the problem for arbitrary initial cell distributions. The method employed exploits the hyperbolic character of the underlying differential operator, and the advanced nature of the functional argument to reduce the problem to a sequence of simple Cauchy problems. The existence of solutions for arbitrary initial distributions is established along with uniqueness. The asymptotic relationship with the steady size distribution is established, and because the solution is known explicitly, higher-order terms in the asymptotics can be readily obtained.

A Notch-dependent molecular circuitry initiates pancreatic endocrine and ductal cell differentiation

DEFF Research Database (Denmark)

Shih, Hung Ping; Kopp, Janel L; Sandhu, Manbir

2012-01-01

necessitates subsequent Sox9 downregulation and evasion from Notch activity via cell-autonomous repression of Sox9 by Ngn3. If high Notch levels are maintained, endocrine progenitors retain Sox9 and undergo ductal fate conversion. Taken together, our findings establish a novel role for Notch in initiating both...

Differential forms on singular varieties De Rham and Hodge theory simplified

CERN Document Server

Ancona, Vincenzo

2005-01-01

Differential Forms on Singular Varieties: De Rham and Hodge Theory Simplified uses complexes of differential forms to give a complete treatment of the Deligne theory of mixed Hodge structures on the cohomology of singular spaces. This book features an approach that employs recursive arguments on dimension and does not introduce spaces of higher dimension than the initial space. It simplifies the theory through easily identifiable and well-defined weight filtrations. It also avoids discussion of cohomological descent theory to maintain accessibility. Topics include classical Hodge theory, differential forms on complex spaces, and mixed Hodge structures on noncompact spaces.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Energy Technology Data Exchange (ETDEWEB)

Goffart, Nicolas [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Kroonen, Jérôme [Human Genetics, CHU and University of Liège, Liège 4000 (Belgium); The T& P Bohnenn Laboratory for Neuro-Oncology, Department of Neurology and Neurosurgery, UMC Utrecht, Utrecht 3556 (Netherlands); Rogister, Bernard, E-mail: Bernard.Register@ulg.ac.be [Laboratory of Developmental Neurobiology, GIGA-Neurosciences Research Center, University of Liège, Liège 4000 (Belgium); Department of Neurology, CHU and University of Liège, Liège 4000 (Belgium); GIGA-Development, Stem Cells and Regenerative Medicine, University of Liège, Liège 4000 (Belgium)

2013-08-14

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

International Nuclear Information System (INIS)

Goffart, Nicolas; Kroonen, Jérôme; Rogister, Bernard

2013-01-01

Glioblastoma multiforme (GBM, WHO grade IV) is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC) properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs) play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology

Glioblastoma-Initiating Cells: Relationship with Neural Stem Cells and the Micro-Environment

Directory of Open Access Journals (Sweden)

Nicolas Goffart

2013-08-01

Full Text Available Glioblastoma multiforme (GBM, WHO grade IV is the most common and lethal subtype of primary brain tumor with a median overall survival of 15 months from the time of diagnosis. The presence in GBM of a cancer population displaying neural stem cell (NSC properties as well as tumor-initiating abilities and resistance to current therapies suggests that these glioblastoma-initiating cells (GICs play a central role in tumor development and are closely related to NSCs. However, it is nowadays still unclear whether GICs derive from NSCs, neural progenitor cells or differentiated cells such as astrocytes or oligodendrocytes. On the other hand, NSCs are located in specific regions of the adult brain called neurogenic niches that have been shown to control critical stem cell properties, to nourish NSCs and to support their self-renewal. This “seed-and-soil” relationship has also been adapted to cancer stem cell research as GICs also require a specific micro-environment to maintain their “stem cell” properties. In this review, we will discuss the controversies surrounding the origin and the identification of GBM stem cells and highlight the micro-environment impact on their biology.

Student initiative: A conceptual analysis

Directory of Open Access Journals (Sweden)

Polovina Nada

2014-01-01

Full Text Available In the description and scientific consideration of the attitude of children and youth towards their education and development, the concept of student initiative has been gaining ground lately, and it is hence the subject of analysis in this paper. The analysis is important because of the discrepancy between the increased efforts of the key educational policy holders to promote the idea about the importance of the development of student initiative and rare acceptance of this idea among theoreticians, researchers and practitioners dealing with the education and development of children and youth. By concretising the features of initiative student behaviour, our aim was, on the one hand, to observe the structural determinants and scientific status of the very concept of an initiative student, and, on the other, to contribute to the understanding of the initiative behaviour in practice. In the first part of the paper we deal with different notions and concretisations of the features of initiative behaviour of children and youth, which includes the consideration of: basic student initiative, academic student initiative, individual student initiative, the capacity for initiative and personal development initiative. In the second part of the paper, we discuss the relations of the concept of student initiative with the similar general concepts (activity/passivity, proactivity, agency and the concepts immediately related to school environment (student involvement, student participation. The results of our analysis indicate that the concept of student initiative has: particular features that differentiate it from similar concepts; the potential to reach the status of a scientific concept, bearing in mind the initial empirical specifications and general empirical verifiability of the yet unverified determinants of the concept. In the concluding part of the paper, we discuss the implications of the conceptual analysis for further research, as well as for

Feasibility study of determining axial stress in ferromagnetic bars using reciprocal amplitude of initial differential susceptibility obtained from static magnetization by permanent magnets

Science.gov (United States)

Deng, Dongge; Wu, Xinjun

2018-03-01

An electromagnetic method for determining axial stress in ferromagnetic bars is proposed. In this method, the tested bar is under the static magnetization provided by permanent magnets. The tested bar do not have to be magnetized up to the technical saturation because reciprocal amplitude of initial differential susceptibility (RAIDS) is adopted as the feature parameter. RAIDS is calculated from the radial magnetic flux density Br Lo = 0.5 at the Lift-off Lo = 0.5 mm, radial magnetic flux density Br Lo = 1 at the Lift-off Lo = 1 mm and axial magnetic flux density Bz Lo = 1 at the Lift-off Lo = 1 mm from the surface of the tested bar. Firstly, the theoretical derivation of RAIDS is carried out according to Gauss' law for magnetism, Ampere's Law and the Rayleigh relation in Rayleigh region. Secondly, the experimental system is set up for a 2-meter length and 20 mm diameter steel bar. Thirdly, an experiment is carried out on the steel bar to analyze the relationship between the obtained RAIDS and the axial stress. Experimental results show that the obtained RAIDS decreases almost linearly with the increment of the axial stress inside the steel bar in the initial elastic region. The proposed method has the potential to determine tensile axial stress in the slender cylindrical ferromagnetic bar.

A Test Set for stiff Initial Value Problem Solvers in the open source software R: Package deTestSet

NARCIS (Netherlands)

Mazzia, F.; Cash, J.R.; Soetaert, K.

2012-01-01

In this paper we present the R package deTestSet that includes challenging test problems written as ordinary differential equations (ODEs), differential algebraic equations (DAEs) of index up to 3 and implicit differential equations (IDES). In addition it includes 6 new codes to solve initial value

Technical Requirements Analysis and Control Systems (TRACS) Initial Operating Capability (IOC) documentation

Science.gov (United States)

Hammond, Dana P.

1991-01-01

The Technical Requirements Analysis and Control Systems (TRACS) software package is described. TRACS offers supplemental tools for the analysis, control, and interchange of project requirements. This package provides the fundamental capability to analyze and control requirements, serves a focal point for project requirements, and integrates a system that supports efficient and consistent operations. TRACS uses relational data base technology (ORACLE) in a stand alone or in a distributed environment that can be used to coordinate the activities required to support a project through its entire life cycle. TRACS uses a set of keyword and mouse driven screens (HyperCard) which imposes adherence through a controlled user interface. The user interface provides an interactive capability to interrogate the data base and to display or print project requirement information. TRACS has a limited report capability, but can be extended with PostScript conventions.

Solutions Stability of Initial Boundary Problem, Modeling of Dynamics of Some Discrete Continuum Mechanical System

Directory of Open Access Journals (Sweden)

D. A. Eliseev

2015-01-01

Full Text Available The solution stability of an initial boundary problem for a linear hybrid system of differential equations, which models the rotation of a rigid body with two elastic rods located in the same plane is studied in the paper. To an axis passing through the mass center of the rigid body perpendicularly to the rods location plane is applied the stabilizing moment proportional to the angle of the system rotation, derivative of the angle, integral of the angle. The external moment provides a feedback. A method of studying the behavior of solutions of the initial boundary problem is proposed. This method allows to exclude from the hybrid system of differential equations partial differential equations, which describe the dynamics of distributed elements of a mechanical system. It allows us to build one equation for an angle of the system rotation. Its characteristic equation defines the stability of solutions of all the system. In the space of feedback-coefficients the areas that provide the asymptotic stability of solutions of the initial boundary problem are built up.

Continuous nowhere differentiable functions the monsters of analysis

CERN Document Server

Jarnicki, Marek

2015-01-01

This book covers the construction, analysis, and theory of continuous nowhere differentiable functions, comprehensively and accessibly. After illuminating the significance of the subject through an overview of its history, the reader is introduced to the sophisticated toolkit of ideas and tricks used to study the explicit continuous nowhere differentiable functions of Weierstrass, Takagi–van der Waerden, Bolzano, and others. Modern tools of functional analysis, measure theory, and Fourier analysis are applied to examine the generic nature of continuous nowhere differentiable functions, as well as linear structures within the (nonlinear) space of continuous nowhere differentiable functions. To round out the presentation, advanced techniques from several areas of mathematics are brought together to give a state-of-the-art analysis of Riemann’s continuous, and purportedly nowhere differentiable, function. For the reader’s benefit, claims requiring elaboration, and open problems, are clearly indicated. An a...

Variable order one-step methods for initial value problems I ...

African Journals Online (AJOL)

A class of variable order one-step integrators is proposed for Initial Value Problems (IVPs) in Ordinary Differential Equations (ODEs). It is based on a rational interpolant. Journal of the Nigerian Association of Mathematical Physics Vol. 10 2006: pp. 91-96 ...

Report Summarizing the Effort Required to Initiate Welding of Irradiated Materials within the Welding Cubicle

Energy Technology Data Exchange (ETDEWEB)

Frederick, Greg [Electric Power Research Institute (EPRI), Palo Alto, CA (United States); Sutton, Benjamin J. [Electric Power Research Institute (EPRI), Palo Alto, CA (United States); Tatman, Jonathan K. [Electric Power Research Institute (EPRI), Palo Alto, CA (United States); Vance, Mark Christopher [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Smith, Allen W. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Clark, Scarlett R. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Feng, Zhili [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Miller, Roger G. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Chen, Jian [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Tang, Wei [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Hu, Xunxiang [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Gibson, Brian T. [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States)

2017-06-01

The advanced welding facility within a hot cell at the Radiochemical Engineering Development Center of Oak Ridge National Laboratory (ORNL), which has been jointly funded by the U.S. Department of Energy (DOE), Office of Nuclear Energy, Light Water Reactor Sustainability Program and the Electric Power Research Institute, Long Term Operations Program and the Welding and Repair Technology Center, is in the final phase of development. Research and development activities in this facility will involve direct testing of advanced welding technologies on irradiated materials in order to address the primary technical challenge of helium induced cracking that can arise when conventional fusion welding techniques are utilized on neutron irradiated stainless steels and nickel-base alloys. This report details the effort that has been required since the beginning of fiscal year 2017 to initiate welding research and development activities on irradiated materials within the hot cell cubicle, which houses welding sub-systems that include laser beam welding (LBW) and friction stir welding (FSW) and provides material containment within the hot cell.

v-erbA overexpression is required to extinguish c-erbA function in erythroid cell differentiation and regulation of the erbA target gene CAII

DEFF Research Database (Denmark)

Disela, C; Glineur, C; Bugge, T

1991-01-01

The v-erbA oncoprotein represents a retrovirus-transduced oncogenic version of the thyroid hormone (T3/T4) receptor c-erbA (type alpha). It contributes to virus-induced erythroleukemia by efficiently arresting differentiation of red cell progenitors and by suppressing transcription of erythrocyte...... of this CAII reporter construct could only be suppressed by very high amounts of v-erbA. Our results suggest that overexpression of v-erbA is required for its function as an oncoprotein....

Hacking cell differentiation: transcriptional rerouting in reprogramming, lineage infidelity and metaplasia.

Science.gov (United States)

Regalo, Gonçalo; Leutz, Achim

2013-08-01

Initiating neoplastic cell transformation events are of paramount importance for the comprehension of regeneration and vanguard oncogenic processes but are difficult to characterize and frequently clinically overlooked. In epithelia, pre-neoplastic transformation stages are often distinguished by the appearance of phenotypic features of another differentiated tissue, termed metaplasia. In haemato/lymphopoietic malignancies, cell lineage ambiguity is increasingly recorded. Both, metaplasia and biphenotypic leukaemia/lymphoma represent examples of dysregulated cell differentiation that reflect a history of trans-differentiation and/or epigenetic reprogramming. Here we compare the similarity between molecular events of experimental cell trans-differentiation as an emerging therapeutic concept, with lineage confusion, as in metaplasia and dysplasia forecasting tumour development. © 2013 The Authors. Published by John Wiley and Sons, Ltd on behalf of EMBO.

Symbolic computation of analytic approximate solutions for nonlinear fractional differential equations

Science.gov (United States)

Lin, Yezhi; Liu, Yinping; Li, Zhibin

2013-01-01

The Adomian decomposition method (ADM) is one of the most effective methods to construct analytic approximate solutions for nonlinear differential equations. In this paper, based on the new definition of the Adomian polynomials, Rach (2008) [22], the Adomian decomposition method and the Padé approximants technique, a new algorithm is proposed to construct analytic approximate solutions for nonlinear fractional differential equations with initial or boundary conditions. Furthermore, a MAPLE software package is developed to implement this new algorithm, which is user-friendly and efficient. One only needs to input the system equation, initial or boundary conditions and several necessary parameters, then our package will automatically deliver the analytic approximate solutions within a few seconds. Several different types of examples are given to illustrate the scope and demonstrate the validity of our package, especially for non-smooth initial value problems. Our package provides a helpful and easy-to-use tool in science and engineering simulations. Program summaryProgram title: ADMP Catalogue identifier: AENE_v1_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AENE_v1_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 12011 No. of bytes in distributed program, including test data, etc.: 575551 Distribution format: tar.gz Programming language: MAPLE R15. Computer: PCs. Operating system: Windows XP/7. RAM: 2 Gbytes Classification: 4.3. Nature of problem: Constructing analytic approximate solutions of nonlinear fractional differential equations with initial or boundary conditions. Non-smooth initial value problems can be solved by this program. Solution method: Based on the new definition of the Adomian polynomials [1], the Adomian decomposition method and the Pad

Numerical methods for hyperbolic differential functional problems

Directory of Open Access Journals (Sweden)

Roman Ciarski

2008-01-01

Full Text Available The paper deals with the initial boundary value problem for quasilinear first order partial differential functional systems. A general class of difference methods for the problem is constructed. Theorems on the error estimate of approximate solutions for difference functional systems are presented. The convergence results are proved by means of consistency and stability arguments. A numerical example is given.

Existence of smooth solutions of multi-term Caputo-type fractional differential equations

OpenAIRE

Sin, Chung-Sik; Cheng, Shusen; Ri, Gang-Il; Kim, Mun-Chol

2017-01-01

This paper deals with the initial value problem for the multi-term fractional differential equation. The fractional derivative is defined in the Caputo sense. Firstly the initial value problem is transformed into a equivalent Volterra-type integral equation under appropriate assumptions. Then new existence results for smooth solutions are established by using the Schauder fixed point theorem.

Ordinary differential equations principles and applications

CERN Document Server

Nandakumaran, A K; George, Raju K

2017-01-01

Written in a clear, logical and concise manner, this comprehensive resource allows students to quickly understand the key principles, techniques and applications of ordinary differential equations. Important topics including first and second order linear equations, initial value problems and qualitative theory are presented in separate chapters. The concepts of two point boundary value problems, physical models and first order partial differential equations are discussed in detail. The text uses tools of calculus and real analysis to get solutions in explicit form. While discussing first order linear systems, linear algebra techniques are used. The real-life applications are interspersed throughout the book to invoke reader's interest. The methods and tricks to solve numerous mathematical problems with sufficient derivations and explanation are provided. The proofs of theorems are explained for the benefit of the readers.

Dynamics of partial differential equations

CERN Document Server

Wayne, C Eugene

2015-01-01

This book contains two review articles on the dynamics of partial differential equations that deal with closely related topics but can be read independently. Wayne reviews recent results on the global dynamics of the two-dimensional Navier-Stokes equations. This system exhibits stable vortex solutions: the topic of Wayne's contribution is how solutions that start from arbitrary initial conditions evolve towards stable vortices. Weinstein considers the dynamics of localized states in nonlinear Schrodinger and Gross-Pitaevskii equations that describe many optical and quantum systems. In this contribution, Weinstein reviews recent bifurcations results of solitary waves, their linear and nonlinear stability properties, and results about radiation damping where waves lose energy through radiation.   The articles, written independently, are combined into one volume to showcase the tools of dynamical systems theory at work in explaining qualitative phenomena associated with two classes of partial differential equ...

Differential equations, mechanics, and computation

CERN Document Server

Palais, Richard S

2009-01-01

This book provides a conceptual introduction to the theory of ordinary differential equations, concentrating on the initial value problem for equations of evolution and with applications to the calculus of variations and classical mechanics, along with a discussion of chaos theory and ecological models. It has a unified and visual introduction to the theory of numerical methods and a novel approach to the analysis of errors and stability of various numerical solution algorithms based on carefully chosen model problems. While the book would be suitable as a textbook for an undergraduate or elementary graduate course in ordinary differential equations, the authors have designed the text also to be useful for motivated students wishing to learn the material on their own or desiring to supplement an ODE textbook being used in a course they are taking with a text offering a more conceptual approach to the subject.

N-th order impulsive integro-differential equations in Banach spaces

Directory of Open Access Journals (Sweden)

Manfeng Hu

2004-03-01

Full Text Available We investigate the maximal and minimal solutions of initial value problem for N-th order nonlinear impulsive integro-differential equation in Banach space by establishing a comparison result and using the upper and lower solutions methods.

Service models and realization of differentiated services networks

Science.gov (United States)

Elizondo, Antonio J.; Garcia Osma, Maria L.; Einsiedler, Hans J.; Roth, Rudolf; Smirnov, Michael I.; Bartoli, Maurizio; Castelli, Paolo; Varga, Balazs; Krampell, Magnus

2001-07-01

Internet Service Providers need to offer Quality of Service (QoS) to fulfil the requirements of applications of their customers. Moreover, in a competitive market environment costs must be low. The selected service model must be effective and low in complexity, but it should still provide high quality and service differentiation, that the current Internet is not yet capable to support. The Differentiated Services (DiffServ) Architecture has been proposed for enabling a range of different Classes of Service (CoS). In the EURESCOM project P1006 several European service providers co-operated to examine various aspects involved in the introduction of service differentiation using the DiffServ approach. The project explored a set of service models for Expedited Forwarding (EF) and Assured Forwarding (AF) and identified requirements for network nodes. Besides, we addressed also measurement issues, charging and accounting issues. Special attention has been devoted to requirements of elastic traffic that adapts its sending rate to congestion state and available bandwidth. QoS mechanisms must prove Transmission Control Protocol (TCP) friendliness. TCP performance degrades under multiple losses. Since RED based queue management may still cause multiple discards, a modified marking scheme called Capped Leaky Bucket is proposed to improve the performance of elastic applications.

Reduction in DNA repair capacity following differentiation of murine proadipocytes

International Nuclear Information System (INIS)

Tofilon, P.J.; Meyn, R.E.

1988-01-01

It has been suggested that terminally differentiated mammalian cells have a decreased DNA repair capacity, compared with proliferating stem cells. To investigate this hypothesis, we have examined γ-ray-induced DNA strand breaks and their repair in the murine proadipocyte stem cell line 3T3-T. By exposure to human plasma, 3T3-T cells can be induced to undergo nonterminal and then terminal differentiation. DNA strand breaks were evaluated using the technique of alkaline elution. No difference was detected among stem, nonterminally differentiated, and terminally differentiated cells in the initial levels of radiation-induced DNA strand breaks. Each of the strand break dose responses increased as a linear function of γ-ray dose. The strand breaks induced by 4 Gy rejoined following biphasic kinetics for each cell type. At each time point examined after irradiation, however, the percentage of strand breaks that had not rejoined in terminally differentiated cells was three to six times greater than in stem cells. The rate of strand break rejoining in nonterminally differentiated cells was of an intermediate value between that of the stem and of the terminally differentiated cells. These results indicate that, at least for 3T3-T cells, differentiated cells have a reduced capacity for DNA repair

Primary root protophloem differentiation requires balanced phosphatidylinositol-4,5-biphosphate levels and systemically affects root branching.

Science.gov (United States)

Rodriguez-Villalon, Antia; Gujas, Bojan; van Wijk, Ringo; Munnik, Teun; Hardtke, Christian S

2015-04-15

Protophloem is a specialized vascular tissue in growing plant organs, such as root meristems. In Arabidopsis mutants with impaired primary root protophloem differentiation, brevis radix (brx) and octopus (ops), meristematic activity and consequently overall root growth are strongly reduced. Second site mutation in the protophloem-specific presumed phosphoinositide 5-phosphatase cotyledon vascular pattern 2 (CVP2), but not in its homolog CVP2-like 1 (CVL1), partially rescues brx defects. Consistent with this finding, CVP2 hyperactivity in a wild-type background recreates a brx phenotype. Paradoxically, however, while cvp2 or cvl1 single mutants display no apparent root defects, the root phenotype of cvp2 cvl1 double mutants is similar to brx or ops, although, as expected, cvp2 cvl1 seedlings contain more phosphatidylinositol-4,5-biphosphate. Thus, tightly balanced phosphatidylinositol-4,5-biphosphate levels appear essential for proper protophloem differentiation. Genetically, OPS acts downstream of phosphatidylinositol-4,5-biphosphate levels, as cvp2 mutation cannot rescue ops defects, whereas increased OPS dose rescues cvp2 cvl1 defects. Finally, all three mutants display higher density and accelerated emergence of lateral roots, which correlates with increased auxin response in the root differentiation zone. This phenotype is also created by application of peptides that suppress protophloem differentiation, clavata3/embryo surrounding region 26 (CLE26) and CLE45. Thus, local changes in the primary root protophloem systemically shape overall root system architecture. © 2015. Published by The Company of Biologists Ltd.

Differential geometry in string models

International Nuclear Information System (INIS)

Alvarez, O.

1986-01-01

In this article the author reviews the differential geometric approach to the quantization of strings. A seminal paper demonstrates the connection between the trace anomaly and the critical dimension. The role played by the Faddeev-Popov ghosts has been instrumental in much of the subsequent work on the quantization of strings. This paper discusses the differential geometry of two dimensional surfaces and its importance in the quantization of strings. The path integral quantization approach to strings will be carefully analyzed to determine the correct effective measure for string theories. The choice of measure for the path integral is determined by differential geometric considerations. Once the measure is determined, the manifest diffeomorphism invariance of the theory will have to be broken by using the Faddeev-Popov ansatz. The gauge fixed theory is studied in detail with emphasis on the role of conformal and gravitational anomalies. In the analysis, the path integral formulation of the gauge fixed theory requires summing over all the distinct complex structures on the manifold

Differential fat harvesting

Directory of Open Access Journals (Sweden)

Sebastian Torres Farr

2014-12-01

Full Text Available Aim: Volume replacement with fillers is regularly performed with the use of diverse volumetric materials to correct different structures around the face, depending on the volume enhancement required and the thickness of the soft tissue envelope. Differential fat harvesting and posterior grafting is performed to place the correct fat parcel size for each target area, expanding the potential applications of fat. Methods: Sixty patients consecutively recruited on a first come basis undergone a facial fat grafting procedure, in private practice setting between March 2012 and October 2013. Fat grafting quantity and quality was predicted for each case. Differential harvesting was performed, with 2 fat parcels size. Processing was performed through washing. Fat infiltration was carried out through small cannulas or needles depending on the treated area. Outcomes were analysed both by the physicians and the patients at 7 days, 1 month, 3 months and 6 months through a perceived satisfaction questionnaire. Parameters considered were downtime or discomfort, skin benefits, volume restoration, reabsorption rate estimated and overall improvement. Results: Full facial differential fat grafting procedure lasted an average of 1.5-2.5 h. Average downtime was 3-4 days. Follow-up was performed to a minimum of 6 months. Both patient and physician overall satisfaction rates were mostly excellent. Adverse events like lumps or irregularities were not encountered. Conclusion: Differential fat harvesting and posterior grafting is a valid alternative, to expand the repertoire of fat use, allow a more homogeneous effect, reduce the potential complications, speed up the process, improve graft survival, and to enhance overall aesthetic outcome.

Differentiating Mouse Embryonic Stem Cells into Embryoid Bodies by Hanging-Drop Cultures.

Science.gov (United States)

Behringer, Richard; Gertsenstein, Marina; Nagy, Kristina Vintersten; Nagy, Andras

2016-12-01

Embryonic stem (ES) cells can develop into many types of differentiated tissues if they are placed into a differentiating environment. This can occur in vivo when the ES cells are injected into or aggregated with an embryo, or in vitro if their culture conditions are modified to induce differentiation. There are an increasing number of differentiating culture conditions that can bias the differentiation of ES cells into desired cell types. Determining the mechanisms that control ES cell differentiation into therapeutically important cell types is a quickly growing area of research. Knowledge gained from these studies may eventually lead to the use of stem cells to repair specific damaged tissues. Many times ES cell differentiation proceeds through an intermediate stage called the embryoid body (EB). EBs are round structures composed of ES cells that have undergone some of the initial stages of differentiation. EBs can then be manipulated further to generate more specific cell types. This protocol describes a method to differentiate ES cells into EBs. It produces EBs of comparable size. This aspect is important because the differentiation processes taking place inside an EB are influenced by its size. © 2016 Cold Spring Harbor Laboratory Press.

VODE, Variable Coefficient Ordinary Differential Equations (ODE) Solver

International Nuclear Information System (INIS)

Brown, P.N.; Hindmarsh, A.C.; Byrne, G.D.

2002-01-01

1 - Description of program or function: VODE is a package of subroutines for the numerical solution of the initial-value problem for systems of first-order ordinary differential equations. The package can be used for either stiff or non-stiff systems. In the stiff case, the Jacobian matrix is treated as full or banded. An algorithm is included for saving and reusing the Jacobian matrix under certain conditions. If storage is limited, this option may be suppressed. 2 - Method of solution - VODE uses the variable-order, variable- coefficient Adams-Moulton method for non-stiff systems and the variable-order, fixed-leading-coefficient Backward Differentiation Formula (BDF) method for stiff systems

MAGI: many-component galaxy initializer

Science.gov (United States)

Miki, Yohei; Umemura, Masayuki

2018-04-01

Providing initial conditions is an essential procedure for numerical simulations of galaxies. The initial conditions for idealized individual galaxies in N-body simulations should resemble observed galaxies and be dynamically stable for time-scales much longer than their characteristic dynamical times. However, generating a galaxy model ab initio as a system in dynamical equilibrium is a difficult task, since a galaxy contains several components, including a bulge, disc, and halo. Moreover, it is desirable that the initial-condition generator be fast and easy to use. We have now developed an initial-condition generator for galactic N-body simulations that satisfies these requirements. The developed generator adopts a distribution-function-based method, and it supports various kinds of density models, including custom-tabulated inputs and the presence of more than one disc. We tested the dynamical stability of systems generated by our code, representing early- and late-type galaxies, with N = 2097 152 and 8388 608 particles, respectively, and we found that the model galaxies maintain their initial distributions for at least 1 Gyr. The execution times required to generate the two models were 8.5 and 221.7 seconds, respectively, which is negligible compared to typical execution times for N-body simulations. The code is provided as open-source software and is publicly and freely available at https://bitbucket.org/ymiki/magi.

Plane waves and spherical means applied to partial differential equations

CERN Document Server

John, Fritz

2004-01-01

Elementary and self-contained, this heterogeneous collection of results on partial differential equations employs certain elementary identities for plane and spherical integrals of an arbitrary function, showing how a variety of results on fairly general differential equations follow from those identities. The first chapter deals with the decomposition of arbitrary functions into functions of the type of plane waves. Succeeding chapters introduce the first application of the Radon transformation and examine the solution of the initial value problem for homogeneous hyperbolic equations with con

Reversal of DDK-Mediated MCM Phosphorylation by Rif1-PP1 Regulates Replication Initiation and Replisome Stability Independently of ATR/Chk1.

Science.gov (United States)

Alver, Robert C; Chadha, Gaganmeet Singh; Gillespie, Peter J; Blow, J Julian

2017-03-07

Dbf4-dependent kinases (DDKs) are required for the initiation of DNA replication, their essential targets being the MCM2-7 proteins. We show that, in Xenopus laevis egg extracts and human cells, hyper-phosphorylation of DNA-bound Mcm4, but not phosphorylation of Mcm2, correlates with DNA replication. These phosphorylations are differentially affected by the DDK inhibitors PHA-767491 and XL413. We show that DDK-dependent MCM phosphorylation is reversed by protein phosphatase 1 (PP1) targeted to chromatin by Rif1. Loss of Rif1 increased MCM phosphorylation and the rate of replication initiation and also compromised the ability of cells to block initiation when challenged with replication inhibitors. We also provide evidence that Rif1 can mediate MCM dephosphorylation at replication forks and that the stability of dephosphorylated replisomes strongly depends on Chk1 activity. We propose that both replication initiation and replisome stability depend on MCM phosphorylation, which is maintained by a balance of DDK-dependent phosphorylation and Rif1-mediated dephosphorylation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

No survival difference after successful {sup 131}I ablation between patients with initially low-risk and high-risk differentiated thyroid cancer

Energy Technology Data Exchange (ETDEWEB)

Verburg, Frederik Anton [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Stokkel, Marcel P.M.; Verkooijen, Robbert B.T. [Leiden University Medical Center, Department of Radiology, Division of Nuclear Medicine, Leiden (Netherlands); Dueren, Christian; Reiners, Christoph [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maeder, Uwe [University of Wuerzburg, Comprehensive Cancer Center, Wuerzburg (Germany); Isselt, Johannes W. van [University Medical Center Utrecht, Department of Radiology and Nuclear Medicine, Utrecht (Netherlands); Marlowe, Robert J. [Spencer-Fontayne Corporation, Jersey City, NJ (United States); Smit, Johannes W. [Leiden University Medical Center, Department of Endocrinology, Leiden (Netherlands); Luster, Markus [University of Ulm, Department of Nuclear Medicine, Ulm (Germany)

2010-02-15

To compare disease-specific survival and recurrence-free survival (RFS) after successful {sup 131}I ablation in patients with differentiated thyroid carcinoma (DTC) between those defined before ablation as low-risk and those defined as high-risk according to the European Thyroid Association 2006 consensus statement. Retrospective data from three university hospitals were pooled. Of 2009 consecutive patients receiving ablation, 509 were identified as successfully ablated based on both undetectable stimulated serum thyroglobulin in the absence of antithyroglobulin antibodies and a negative diagnostic whole-body scan in a follow-up examination conducted 8.1{+-}4.6 months after ablation. Of these 509 patients, 169 were defined as high-risk. After a mean follow-up of 81{+-}64 months (range 4-306 months), only three patients had died of DTC, rendering assessment of disease-specific survival differences impossible. Of the 509 patients, 12 (2.4%) developed a recurrence a mean 35 months (range 12-59 months) after ablation. RFS for the duration of follow-up was 96.6% according to the Kaplan-Meier method. RFS did not differ between high-risk and low-risk patients (p=0.68). RFS differed slightly but significantly between those with papillary and those with follicular thyroid carcinoma (p=0.03) and between those aged {<=}45 years those aged >45 years at diagnosis (p=0.018). After (near) total thyroidectomy and successful {sup 131}I ablation, RFS does not differ between patients classified as high-risk and those classified as low-risk based on TNM stage at diagnosis. Consequently, the follow-up protocol should be determined on the basis of the result of initial treatment rather than on the initial tumour classification. (orig.)

Paired related homeobox 1 transactivates dopamine D2 receptor to maintain propagation and tumorigenicity of glioma-initiating cells

Institute of Scientific and Technical Information of China (English)

Yamu Li; Ying Liu; Shu Li; Xiaobing Jiang; Guangwei Du; Yan Zhou; Wen Wang; Fangyu Wang; Qiushuang Wu; Wei Li; Xiaoling Zhong; Kuan Tian; Tao Zeng; Liang Gao

2017-01-01

Glioblastoma multiforme (GBM) is a highly invasive brain tumor with limited therapeutic means and poor prognosis.Recent studies indicate that glioma-initiating cells/glioma stem cells (GICs/GSCs) may be responsible for tumor initiation,infiltration,and recurrence.GlCs could aberrantly employ molecular machinery balancing self-renewal and differentiation of embryonic neural precursors.Here,we find that paired related homeobox 1 (PRRX1),a homeodomain transcription factor that was previously reported to control skeletal development,is expressed in cortical neural progenitors and is required for their self-renewal and proper differentiation.Further,PRRX1 is overrepresented in glioma samples and labels GlCs.Glioma cells and GlCs depleted with PRRX1 could not propagate in vitro or form tumors in the xenograft mouse model.The GIC self-renewal function regulated by PRRX1 is mediated by dopamine D2 receptor (DRD2).PRRX1 directly binds to the DRD2 promoter and transactivates its expression in GlCs.Blockage of the DRD2 signaling hampers GIC self-renewal,whereas its overexpression restores the propagating and tumorigenic potential of PRRX1-depleted GlCs.Finally,PRRX1 potentiates GlCs via DRD2-mediated extracellular signal-related kinase (ERK) and AKT activation.Thus,our study suggests that therapeutic targeting the PRRX1-DRD2-ERK/AKT axis in GlCs is a promising strategy for treating GBMs.

Procalcitonin and C-reactive protein cannot differentiate bacterial or viral infection in COPD exacerbation requiring emergency department visits

Directory of Open Access Journals (Sweden)

Chang CH

2015-04-01

Full Text Available Chih-Hao Chang,1 Kuo-Chien Tsao,2,3 Han-Chung Hu,1,4 Chung-Chi Huang,1,4 Kuo-Chin Kao,1,4 Ning-Hung Chen,1,4 Cheng-Ta Yang,1,4 Ying-Huang Tsai,4,5 Meng-Jer Hsieh4,51Department of Pulmonary and Critical Care Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Chang-Gung University College of Medicine, Taoyuan, Taiwan; 2Department of Laboratory Medicine, Linkou Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation; 3Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan; 4Department of Respiratory Therapy, Chang-Gung University, Taoyuan, Taiwan; 5Department of Pulmonary and Critical Care Medicine, Chiayi Chang-Gung Memorial Hospital, Chang-Gung Medical Foundation, Puzi City, TaiwanBackground: Viral and bacterial infections are the most common causes of chronic obstructive pulmonary disease (COPD exacerbations. Whether serum inflammatory markers can differentiate bacterial from virus infection in patients with COPD exacerbation requiring emergency department (ED visits remains controversial.Methods: Viral culture and polymerase chain reaction (PCR were used to identify the viruses in the oropharynx of patients with COPD exacerbations. The bacteria were identified by the semiquantitative culture of the expectorated sputum. The peripheral blood white blood cell (WBC counts, serum C-reactive protein (CRP, procalcitonin (PCT, and clinical symptoms were compared among patients with different types of infections.Results: Viruses were isolated from 16 (22.2% of the 72 patients enrolled. The most commonly identified viruses were parainfluenza type 3, influenza A, and rhinovirus. A total of 30 (41.7% patients had positive bacterial cultures, with the most commonly found bacteria being Haemophilus influenzae and Haemophilus parainfluenzae. Five patients (6.9% had both positive sputum cultures and virus identification. The WBC, CRP, and PCT levels of the bacteria-positive and bacteria

Autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast.

Science.gov (United States)

Matsuhara, Hirotada; Yamamoto, Ayumu

2016-01-01

Autophagy is a conserved intracellular degradation system, which contributes to development and differentiation of various organisms. Yeast cells undergo meiosis under nitrogen-starved conditions and require autophagy for meiosis initiation. However, the precise roles of autophagy in meiosis remain unclear. Here, we show that autophagy is required for efficient meiosis progression and proper meiotic chromosome segregation in fission yeast. Autophagy-defective strains bearing a mutation in the autophagy core factor gene atg1, atg7, or atg14 exhibit deformed nuclear structures during meiosis. These mutant cells require an extracellular nitrogen supply for meiosis progression following their entry into meiosis and show delayed meiosis progression even with a nitrogen supply. In addition, they show frequent chromosome dissociation from the spindle together with spindle overextension, forming extra nuclei. Furthermore, Aurora kinase, which regulates chromosome segregation and spindle elongation, is significantly increased at the centromere and spindle in the mutant cells. Aurora kinase down-regulation eliminated delayed initiation of meiosis I and II, chromosome dissociation, and spindle overextension, indicating that increased Aurora kinase activity may cause these aberrances in the mutant cells. Our findings show a hitherto unrecognized relationship of autophagy with the nuclear structure, regulation of cell cycle progression, and chromosome segregation in meiosis. © 2015 The Molecular Biology Society of Japan and Wiley Publishing Asia Pty Ltd.

Digital differential confocal microscopy based on spatial shift transformation.

Science.gov (United States)

Liu, J; Wang, Y; Liu, C; Wilson, T; Wang, H; Tan, J

2014-11-01

Differential confocal microscopy is a particularly powerful surface profilometry technique in industrial metrology due to its high axial sensitivity and insensitivity to noise. However, the practical implementation of the technique requires the accurate positioning of point detectors in three-dimensions. We describe a simple alternative based on spatial transformation of a through-focus series of images obtained from a homemade beam scanning confocal microscope. This digital differential confocal microscopy approach is described and compared with the traditional Differential confocal microscopy approach. The ease of use of the digital differential confocal microscopy system is illustrated by performing measurements on a 3D standard specimen. © 2014 The Authors Journal of Microscopy © 2014 Royal Microscopical Society.

Solution of initial value problems using ndsolve of mathematica ...

African Journals Online (AJOL)

In the paper, the hyperbolic equations of the form (1) are approximated by the semi-finite difference schemes O(h2) and O(h4) accurate. The resulting two stiff systems of ordinary differential equations with initial conditions are solved by a Mathematica modules utilizing the function NDSolve. The stiffness ratios of the ...

Hydrostatic self-locking bevel differential gear; Hydrostatisch selbstsperrendes Kegelraddifferentialgetriebe

Energy Technology Data Exchange (ETDEWEB)

Kalmbach, K.

2001-07-01

The product range of the rail vehicle industry comprises the construction of railroad material for long-distance and short-distance transport. This includes, for example, locomotives and cars, subway, light railway and tramway cars as well as rail vehicle equipment. The development of the industry is determined by the demand for transport services and government actions for the extension of railways and procurement of suitable vehicle types. In contrast to road vehicles, differential gears are only used in a negligible percentage of rail vehicles. Primarily in the short-distance rail transport sector, the demand for differential gears is growing due to increased drive power, smaller wheel diameters, lower vehicle mass with higher load capacity, the introduction of low-floor technology as well as the requirement of employing ever more quiet vehicles. In hydrostatic self-locking differential gears, oil is supplied to the gears within the differential gearbox. They only rotate relative to each other when the differential gear performs a compensation movement. In this case, oil is transported in the tooth space to the meshing of the gears, where it is displaced due to the meshing and must drain through tight gaps. The pressure generated by this process acts against the compensation movement of the gear, and the drive torque is transmitted to the wheel that has the higher friction. The achievable locking torque is linearly dependent on the differential speed of the drive wheel. This locking effect is achieved without wear-prone components and works automatically without active external intervention. The design space required corresponds to that of conventional differential gears, as the locking effect is integrated in the existing design. (orig.)

Group I Paks Promote Skeletal Myoblast Differentiation In Vivo and In Vitro

DEFF Research Database (Denmark)

Joseph, Giselle A; Lu, Min; Radu, Maria

2017-01-01

fusion in Drosophila We report that both Pak1 and Pak2 are activated during mammalian myoblast differentiation. One pathway of activation is initiated by N-cadherin ligation and involves the cadherin coreceptor Cdo with its downstream effector, Cdc42. Individual genetic deletion of Pak1 and Pak2 in mice....... Furthermore, primary myoblasts lacking Pak1 and Pak2 display delayed expression of myogenic differentiation markers and myotube formation. These results identify Pak1 and Pak2 as redundant regulators of myoblast differentiation in vitro and in vivo and as components of the promyogenic Ncad/Cdo/Cdc42 signaling...

Mapping of ESE-1 subdomains required to initiate mammary epithelial cell transformation via a cytoplasmic mechanism

Directory of Open Access Journals (Sweden)

Tentler John J

2011-08-01

Full Text Available Abstract Background The ETS family transcription factor ESE-1 is often overexpressed in human breast cancer. ESE-1 initiates transformation of MCF-12A cells via a non-transcriptional, cytoplasmic process that is mediated by a unique 40-amino acid serine and aspartic acid rich (SAR subdomain, whereas, ESE-1's nuclear transcriptional property is required to maintain the transformed phenotype of MCF7, ZR-75-1 and T47D breast cancer cells. Results To map the minimal functional nuclear localization (NLS and nuclear export (NES signals, we fused in-frame putative NLS and NES motifs between GFP and the SAR domain. Using these GFP constructs as reporters of subcellular localization, we mapped a single NLS to six basic amino acids (242HGKRRR247 in the AT-hook and two CRM1-dependent NES motifs, one to the pointed domain (NES1: 102LCNCALEELRL112 and another to the DNA binding domain (DBD, (NES2: 275LWEFIRDILI284. Moreover, analysis of a putative NLS located in the DBD (316GQKKKNSN323 by a similar GFP-SAR reporter or by internal deletion of the DBD, revealed this sequence to lack NLS activity. To assess the role of NES2 in regulating ESE-1 subcellular localization and subsequent transformation potency, we site-specifically mutagenized NES2, within full-length GFP-ESE-1 and GFP-NES2-SAR reporter constructs. These studies show that site-specific mutation of NES2 completely abrogates ESE-1 transforming activity. Furthermore, we show that exclusive cytoplasmic targeting of the SAR domain is sufficient to initiate transformation, and we report that an intact SAR domain is required, since block mutagenesis reveals that an intact SAR domain is necessary to maintain its full transforming potency. Finally, using a monoclonal antibody targeting the SAR domain, we demonstrate that the SAR domain contains a region accessible for protein - protein interactions. Conclusions These data highlight that ESE-1 contains NLS and NES signals that play a critical role in

High Order A-stable Continuous General Linear Methods for Solution of Systems of Initial Value Problems in ODEs

Directory of Open Access Journals (Sweden)

Dauda GuliburYAKUBU

2012-12-01

Full Text Available Accurate solutions to initial value systems of ordinary differential equations may be approximated efficiently by Runge-Kutta methods or linear multistep methods. Each of these has limitations of one sort or another. In this paper we consider, as a middle ground, the derivation of continuous general linear methods for solution of stiff systems of initial value problems in ordinary differential equations. These methods are designed to combine the advantages of both Runge-Kutta and linear multistep methods. Particularly, methods possessing the property of A-stability are identified as promising methods within this large class of general linear methods. We show that the continuous general linear methods are self-starting and have more ability to solve the stiff systems of ordinary differential equations, than the discrete ones. The initial value systems of ordinary differential equations are solved, for instance, without looking for any other method to start the integration process. This desirable feature of the proposed approach leads to obtaining very high accuracy of the solution of the given problem. Illustrative examples are given to demonstrate the novelty and reliability of the methods.

Efficacy of respiratory endoscopy on subjects requiring further detailed examinations after initial asbestos-related disease screening

International Nuclear Information System (INIS)

Fukuoka, Kazuya; Uesaka, Ayuko; Kuribayashi, Kozo

2007-01-01

We evaluated the efficacy of respiratory endoscopy on subjects requiring further detailed examinations as a result of initial asbestos-related disease screening. The subjects consisted of 132 participants who underwent asbestos-related disease screening in our hospital between July 2005 and March 2006. According to their history of screening, the participants were classified into the initial screening group and the second screening group. The former consisted of 76 participants without prior screening, while the latter consisted of 56 participants who were referred to our hospital for the detailed examinations as a result of initial screening undergone elsewhere. The participants were examined concerning their history of asbestos exposure, and then underwent chest X-ray followed by chest computed tomography (CT). Respiratory endoscopic examinations were mainly performed in participants with suspected chest malignancies. There were no significant differences in the distribution of age or gender between the two screening groups. In both screening groups, more than 70% of the participants had a history of occupational exposure to asbestos. Radiological abnormalities were observed in 110 (83%) of all participants. Asbestos-related diseases were detected in a total of 90 (68%) cases. The breakdown of the 90 cases by disease was as follows: 60 cases had pleural plaque, 13 pulmonary fibrosis, 5 lung cancer (LC), 4 benign asbestos pleurisy, 4 round atelectasis, 2 diffuse pleural thickening, and 2 malignant pleural mesothelioma (MPM). The disease detection rate of LC and MPM was 3.8% and 1.5%, respectively. Respiratory endoscopic examinations were performed in a total of 15 cases. The breakdown of the 15 cases by examination was as follows: bronchoscopy was performed in 6 cases, thoracoscopy including video-assisted thoracoscopic surgery (VATS) in 8, and mediastinoscopy in 4. Two cases with early LC were diagnosed by videothoracoscopic lung biopsy. A diagnosis of MPM was

Distant metastases in differentiated thyroid carcinoma: diagnosis and treatment

International Nuclear Information System (INIS)

Schmidt, A.; Cross, G.; Pitoia, F.

2017-01-01

Distant metastases occur in less than 10% of patients with differentiated thyroid carcinoma. In these patients, overall survival at 10 years is considerably reduced. Whereas cure is the initial goal of treatment, stabilisation of the disease and management of symptoms have become the primary objective in many patients with persistent radio-iodine refractory progressive disease. In the last decade, several targeted therapies have shown encouraging results in patients with advanced disease. The objective of this review is to describe the characteristics, diagnosis, overall survival, and the local and systemic available treatments for patients with distant metastases from differentiated thyroid cancer. (authors) [es

Differentiation of Self, Personal Adjustment, Problem Solving, and Ethnic Group Belonging among Persons of Color.

Science.gov (United States)

Skowron, Elizabeth A.

2004-01-01

This study focused on examining the cross-cultural validity of Bowen family systems theory (M. Bowen, 1978), namely differentiation of self for individuals of color. Ethnic minority men and women completed measures of differentiation of self, ethnic group belonging, and 3 indices of personal adjustment. Initial support for the cross-cultural…

Periodicity and positivity of a class of fractional differential equations.

Science.gov (United States)

Ibrahim, Rabha W; Ahmad, M Z; Mohammed, M Jasim

2016-01-01

Fractional differential equations have been discussed in this study. We utilize the Riemann-Liouville fractional calculus to implement it within the generalization of the well known class of differential equations. The Rayleigh differential equation has been generalized of fractional second order. The existence of periodic and positive outcome is established in a new method. The solution is described in a fractional periodic Sobolev space. Positivity of outcomes is considered under certain requirements. We develop and extend some recent works. An example is constructed.

On the hierarchy of partially invariant submodels of differential equations

OpenAIRE

Golovin, Sergey V.

2007-01-01

It is noticed, that partially invariant solution (PIS) of differential equations in many cases can be represented as an invariant reduction of some PIS of the higher rank. This introduce a hierarchic structure in the set of all PISs of a given system of differential equations. By using this structure one can significantly decrease an amount of calculations required in enumeration of all PISs for a given system of partially differential equations. An equivalence of the two-step and the direct ...

Innovating the differential pressure switch

International Nuclear Information System (INIS)

Ostrelich, M.

2010-01-01

When Barton Jones filed for patent 2, 400, 048 in 1943 for his liquid filled dual-bellows differential pressure unit, he initiated an engineering concept that has endured and has been validated for rugged, reliable and accurate measurement and control. Although based on established engineering principles the execution of the concept to instrumentation products has resisted innovation until present time. With the objective of preserving the established engineering principles and maintaining the same form fit and function of the original instrumentation, it was necessary to apply present day component availability and manufacturing techniques to construct instrumentation that has improved reliability and facilitates assembly and calibration. The original component design is presented and is compared with the improved equivalent. The application of this instrumentation utilized for the control of Nuclear Power Plants has provided the initiative for component innovation. (authors)

Pak3 promotes cell cycle exit and differentiation of β-cells in the embryonic pancreas and is necessary to maintain glucose homeostasis in adult mice.

Science.gov (United States)

Piccand, Julie; Meunier, Aline; Merle, Carole; Jia, Zhengping; Barnier, Jean-Vianney; Gradwohl, Gérard

2014-01-01

The transcription factor neurogenin3 (Ngn3) triggers islet cell differentiation in the developing pancreas. However, little is known about the molecular mechanisms coupling cell cycle exit and differentiation in Ngn3(+) islet progenitors. We identified a novel effector of Ngn3 endocrinogenic function, the p21 protein-activated kinase Pak3, known to control neuronal differentiation and implicated in X-linked intellectual disability in humans. We show that Pak3 expression is initiated in Ngn3(+) endocrine progenitor cells and next maintained in maturing hormone-expressing cells during pancreas development as well as in adult islet cells. In Pak3-deficient embryos, the proliferation of Ngn3(+) progenitors and β-cells is transiently increased concomitantly with an upregulation of Ccnd1. β-Cell differentiation is impaired at E15.5 but resumes at later stages. Pak3-deficient mice do not develop overt diabetes but are glucose intolerant under high-fat diet (HFD). In the intestine, Pak3 is expressed in enteroendocrine cells but is not necessary for their differentiation. Our results indicate that Pak3 is a novel regulator of β-cell differentiation and function. Pak3 acts downstream of Ngn3 to promote cell cycle exit and differentiation in the embryo by a mechanism that might involve repression of Ccnd1. In the adult, Pak3 is required for the proper control of glucose homeostasis under challenging HFD.

Backward-stochastic-differential-equation approach to modeling of gene expression.

Science.gov (United States)

Shamarova, Evelina; Chertovskih, Roman; Ramos, Alexandre F; Aguiar, Paulo

2017-03-01

In this article, we introduce a backward method to model stochastic gene expression and protein-level dynamics. The protein amount is regarded as a diffusion process and is described by a backward stochastic differential equation (BSDE). Unlike many other SDE techniques proposed in the literature, the BSDE method is backward in time; that is, instead of initial conditions it requires the specification of end-point ("final") conditions, in addition to the model parametrization. To validate our approach we employ Gillespie's stochastic simulation algorithm (SSA) to generate (forward) benchmark data, according to predefined gene network models. Numerical simulations show that the BSDE method is able to correctly infer the protein-level distributions that preceded a known final condition, obtained originally from the forward SSA. This makes the BSDE method a powerful systems biology tool for time-reversed simulations, allowing, for example, the assessment of the biological conditions (e.g., protein concentrations) that preceded an experimentally measured event of interest (e.g., mitosis, apoptosis, etc.).

Cognitive-Behavioral Therapy for Depression Using Mind Over Mood: CBT Skill Use and Differential Symptom Alleviation.

Science.gov (United States)

Hawley, Lance L; Padesky, Christine A; Hollon, Steven D; Mancuso, Enza; Laposa, Judith M; Brozina, Karen; Segal, Zindel V

2017-01-01

Cognitive-behavioral therapy (CBT) for depression is highly effective. An essential element of this therapy involves acquiring and utilizing CBT skills; however, it is unclear whether the type of CBT skill used is associated with differential symptom alleviation. Outpatients (N = 356) diagnosed with a primary mood disorder received 14 two-hour group sessions of CBT for depression, using the Mind Over Mood protocol. In each session, patients completed the Beck Depression Inventory and throughout the week they reported on their use of CBT skills: behavioral activation (BA), cognitive restructuring (CR), and core belief (CB) strategies. Bivariate latent difference score (LDS) longitudinal analyses were used to examine patterns of differential skill use and subsequent symptom change, and multigroup LDS analyses were used to determine whether longitudinal associations differed as a function of initial depression severity. Higher levels of BA use were associated with a greater subsequent decrease in depressive symptoms for patients with mild to moderate initial depression symptoms relative to those with severe symptoms. Higher levels of CR use were associated with a greater subsequent decrease in depressive symptoms, whereas higher levels of CB use were followed by a subsequent increase in depressive symptoms, regardless of initial severity. Results indicated that the type of CBT skill used is associated with differential patterns of subsequent symptom change. BA use was associated with differential subsequent change as a function of initial severity (patients with less severe depression symptoms demonstrated greater symptom improvement), whereas CR use was associated with symptom alleviation and CB use with an increase in subsequent symptoms as related to initial severity. Copyright © 2016. Published by Elsevier Ltd.

Elevated serum alpha-fetoprotein in poorly differentiated adenocarcinoma with neuroendocrine differentiation of the ascending colon: a case report.

Science.gov (United States)

Lin, Hung-Hsin; Chang, Chia-Chu; Yang, Shung-Haur; Chang, Shih-Ching; Chen, Wei-Shone; Liang, Wen-Yih; Lin, Jen-Kou; Jiang, Jeng-Kai

2016-03-15

Colorectal cancer (CRC) is the most common form of cancer and the third leading cause of death in Taiwan. Serum alpha-fetoprotein (AFP) has been extensively used as a biomarker for hepatocellular carcinoma (HCC) and yolk sac tumors. This case report presents a 90-year-old woman with right abdominal pain and poor appetite for 1 week. The computed tomography (CT) showed wall thickening in the proximal ascending colon with ruptured appendicitis. Preoperative serum AFP was high. There was no definite liver metastasis or other abnormal findings in the hepatobiliary systems. After initial empirical antibiotic treatment, we performed laparoscopic right hemicolectomy. The pathological assessment was poorly differentiated adenocarcinoma with neuroendocrine differentiation in the ascending colon. The tumor cells did not produce AFP. Amazingly, the follow-up serum AFP level 1 month after the surgery declined to normal range. The patient had an uneventful course after the surgery and was free of recurrence or metastasis within 5 months of follow-up. AFP may be a useful tumor marker in poorly differentiated colorectal cancer with neuroendocrine component patients and a prediction of early treatment response.

Parent-child communication and marijuana initiation: evidence using discrete-time survival analysis.

Science.gov (United States)

Nonnemaker, James M; Silber-Ashley, Olivia; Farrelly, Matthew C; Dench, Daniel

2012-12-01

This study supplements existing literature on the relationship between parent-child communication and adolescent drug use by exploring whether parental and/or adolescent recall of specific drug-related conversations differentially impact youth's likelihood of initiating marijuana use. Using discrete-time survival analysis, we estimated the hazard of marijuana initiation using a logit model to obtain an estimate of the relative risk of initiation. Our results suggest that parent-child communication about drug use is either not protective (no effect) or - in the case of youth reports of communication - potentially harmful (leading to increased likelihood of marijuana initiation). Copyright © 2012 Elsevier Ltd. All rights reserved.

Measurement-based perturbation theory and differential equation parameter estimation with applications to satellite gravimetry

Science.gov (United States)

Xu, Peiliang

2018-06-01

The numerical integration method has been routinely used by major institutions worldwide, for example, NASA Goddard Space Flight Center and German Research Center for Geosciences (GFZ), to produce global gravitational models from satellite tracking measurements of CHAMP and/or GRACE types. Such Earth's gravitational products have found widest possible multidisciplinary applications in Earth Sciences. The method is essentially implemented by solving the differential equations of the partial derivatives of the orbit of a satellite with respect to the unknown harmonic coefficients under the conditions of zero initial values. From the mathematical and statistical point of view, satellite gravimetry from satellite tracking is essentially the problem of estimating unknown parameters in the Newton's nonlinear differential equations from satellite tracking measurements. We prove that zero initial values for the partial derivatives are incorrect mathematically and not permitted physically. The numerical integration method, as currently implemented and used in mathematics and statistics, chemistry and physics, and satellite gravimetry, is groundless, mathematically and physically. Given the Newton's nonlinear governing differential equations of satellite motion with unknown equation parameters and unknown initial conditions, we develop three methods to derive new local solutions around a nominal reference orbit, which are linked to measurements to estimate the unknown corrections to approximate values of the unknown parameters and the unknown initial conditions. Bearing in mind that satellite orbits can now be tracked almost continuously at unprecedented accuracy, we propose the measurement-based perturbation theory and derive global uniformly convergent solutions to the Newton's nonlinear governing differential equations of satellite motion for the next generation of global gravitational models. Since the solutions are global uniformly convergent, theoretically speaking

Supervised Semi-Automated Data Analysis Software for Gas Chromatography / Differential Mobility Spectrometry (GC/DMS) Metabolomics Applications.

Science.gov (United States)

Peirano, Daniel J; Pasamontes, Alberto; Davis, Cristina E

2016-09-01

Modern differential mobility spectrometers (DMS) produce complex and multi-dimensional data streams that allow for near-real-time or post-hoc chemical detection for a variety of applications. An active area of interest for this technology is metabolite monitoring for biological applications, and these data sets regularly have unique technical and data analysis end user requirements. While there are initial publications on how investigators have individually processed and analyzed their DMS metabolomic data, there are no user-ready commercial or open source software packages that are easily used for this purpose. We have created custom software uniquely suited to analyze gas chromatograph / differential mobility spectrometry (GC/DMS) data from biological sources. Here we explain the implementation of the software, describe the user features that are available, and provide an example of how this software functions using a previously-published data set. The software is compatible with many commercial or home-made DMS systems. Because the software is versatile, it can also potentially be used for other similarly structured data sets, such as GC/GC and other IMS modalities.

Two Ways to Examine Differential Constitutive Equations: Initiated on Steady or Initiated on Unsteady (LAOS Shear Characteristics

Directory of Open Access Journals (Sweden)

Jana Zelenkova

2017-06-01

Full Text Available The exponential Phan–Tien and Tanner (PTT, Giesekus, Leonov, and modified extended Pom–Pom (mXPP differential constitutive models are evaluated in two ways: with regard to steady shear characteristics and with regard to large amplitude oscillatory shear characteristics of a solution of poly(ethylene oxide in dimethyl sulfoxide. Efficiency of the models with nonlinear parameters optimized with respect to steady shear measurements is evaluated by their ability to describe large amplitude oscillatory shear (LAOS characteristics. The reciprocal problem is also analyzed: The nonlinear parameters are optimized with respect to the LAOS measurements, and the models are confronted with the steady shear characteristics. In this case, optimization is based on the LAOS measurements and equal emphasis is placed on both real and imaginary parts of the stress amplitude. The results show that the chosen models are not adequately able to fit the LAOS characteristics if the optimization of nonlinear parameters is based on steady shear measurements. It follows that the optimization of nonlinear parameters is much more responsible if it is carried out with respect to the LAOS data. In this case, when the optimized parameters are used for a description of steady shear characteristics, efficiency of the individual models as documented differs.

Aging memories: differential decay of episodic memory components.

Science.gov (United States)

Talamini, Lucia M; Gorree, Eva

2012-05-17

Some memories about events can persist for decades, even a lifetime. However, recent memories incorporate rich sensory information, including knowledge on the spatial and temporal ordering of event features, while old memories typically lack this "filmic" quality. We suggest that this apparent change in the nature of memories may reflect a preferential loss of hippocampus-dependent, configurational information over more cortically based memory components, including memory for individual objects. The current study systematically tests this hypothesis, using a new paradigm that allows the contemporaneous assessment of memory for objects, object pairings, and object-position conjunctions. Retention of each memory component was tested, at multiple intervals, up to 3 mo following encoding. The three memory subtasks adopted the same retrieval paradigm and were matched for initial difficulty. Results show differential decay of the tested episodic memory components, whereby memory for configurational aspects of a scene (objects' co-occurrence and object position) decays faster than memory for featured objects. Interestingly, memory requiring a visually detailed object representation decays at a similar rate as global object recognition, arguing against interpretations based on task difficulty and against the notion that (visual) detail is forgotten preferentially. These findings show that memories undergo qualitative changes as they age. More specifically, event memories become less configurational over time, preferentially losing some of the higher order associations that are dependent on the hippocampus for initial fast encoding. Implications for theories of long-term memory are discussed.

Differential Precipitation and Solubilization of Proteins.

Science.gov (United States)

Ryan, Barry J; Kinsella, Gemma K

2017-01-01

Differential protein precipitation is a rapid and economical step in protein purification and is based on exploiting the inherent physicochemical properties of the polypeptide. Precipitation of recombinant proteins, lysed from the host cell, is commonly used to concentrate the protein of choice before further polishing steps with more selective purification columns (e.g., His-Tag, Size Exclusion, etc.). Recombinant proteins can also precipitate naturally as inclusion bodies due to various influences during overexpression in the host cell. Although this phenomenon permits easier initial separation from native proteins, these inclusion bodies must carefully be differentially solubilized so as to reform functional, correctly folded proteins. Here, appropriate bioinformatics tools to aid in understanding a protein's propensity to aggregate and solubilize are explored as a backdrop for a typical protein extraction, precipitation, and selective resolubilization procedure, based on a recombinantly expressed protein.

Protein tyrosine phosphatase 1B (PTP1B) is required for cardiac lineage differentiation of mouse embryonic stem cells.

Science.gov (United States)

Eshkiki, Zahra Shokati; Ghahremani, Mohammad Hossein; Shabani, Parisa; Firuzjaee, Sattar Gorgani; Sadeghi, Asie; Ghanbarian, Hossein; Meshkani, Reza

2017-01-01

Protein tyrosine phosphatase 1B (PTP1B) has been shown to regulate multiple cellular events such as differentiation, cell growth, and proliferation; however, the role of PTP1B in differentiation of embryonic stem (ES) cells into cardiomyocytes remains unexplored. In the present study, we investigated the effects of PTP1B inhibition on differentiation of ES cells into cardiomyocytes. PTP1B mRNA and protein levels were increased during the differentiation of ES cells into cardiomyocytes. Accordingly, a stable ES cell line expressing PTP1B shRNA was established. In vitro, the number and size of spontaneously beating embryoid bodies were significantly decreased in PTP1B-knockdown cells, compared with the control cells. Decreased expression of cardiac-specific markers Nkx2-5, MHC-α, cTnT, and CX43, as assessed by real-time PCR analysis, was further confirmed by immunocytochemistry of the markers. The results also showed that PTP1B inhibition induced apoptosis in both differentiated and undifferentiated ES cells, as presented by increasing the level of cleaved caspase-3, cytochrome C, and cleaved PARP. Further analyses revealed that PTP1B inhibition did not change proliferation and pluripotency of undifferentiated ES cells. Taken together, the data presented here suggest that PTP1B is essential for proper differentiation of ES cells into cardiomyocytes.

Alternative Splicing of G9a Regulates Neuronal Differentiation

Directory of Open Access Journals (Sweden)

Ana Fiszbein

2016-03-01

Full Text Available Chromatin modifications are critical for the establishment and maintenance of differentiation programs. G9a, the enzyme responsible for histone H3 lysine 9 dimethylation in mammalian euchromatin, exists as two isoforms with differential inclusion of exon 10 (E10 through alternative splicing. We find that the G9a methyltransferase is required for differentiation of the mouse neuronal cell line N2a and that E10 inclusion increases during neuronal differentiation of cultured cells, as well as in the developing mouse brain. Although E10 inclusion greatly stimulates overall H3K9me2 levels, it does not affect G9a catalytic activity. Instead, E10 increases G9a nuclear localization. We show that the G9a E10+ isoform is necessary for neuron differentiation and regulates the alternative splicing pattern of its own pre-mRNA, enhancing E10 inclusion. Overall, our findings indicate that by regulating its own alternative splicing, G9a promotes neuron differentiation and creates a positive feedback loop that reinforces cellular commitment to differentiation.

Understanding and responding the students in learning mathematics through the differentiated instruction

Science.gov (United States)

Hapsari, T.; Darhim; Dahlan, J. A.

2018-05-01

This research discusses the differentiated instruction, a mathematic learning which is as expected by the students in connection with the differentiated instruction itself, its implementation, and the students’ responses. This research employs a survey method which involves 62 students as the research respondents. The mathematics learning types required by the students and their responses to the differentiated instruction are examined through questionnaire and interview. The mathematics learning types in orderly required by the students, from the highest frequency cover the easily understood instructions, slowly/not rushing teaching, fun, not complicated, interspersed with humour, various question practices, not too serious, and conducive class atmosphere for the instructions. Implementing the differentiated instruction is not easy. The teacher should be able to constantly assess the students, s/he should have good knowledge of relevant materials and instructions, and properly prepare the instructions, although it is time-consuming. The differentiated instruction is implemented on the instructions of numerical pattern materials. The strategies implemented are flexible grouping, tiered assignment, and compacting. The students positively respond the differentiated learning instruction that they become more motivated and involved in the instruction.

Green's matrix for a second-order self-adjoint matrix differential operator

International Nuclear Information System (INIS)

Sisman, Tahsin Cagri; Tekin, Bayram

2010-01-01

A systematic construction of the Green's matrix for a second-order self-adjoint matrix differential operator from the linearly independent solutions of the corresponding homogeneous differential equation set is carried out. We follow the general approach of extracting the Green's matrix from the Green's matrix of the corresponding first-order system. This construction is required in the cases where the differential equation set cannot be turned to an algebraic equation set via transform techniques.

Modeling Solution of Nonlinear Dispersive Partial Differential Equations using the Marker Method

International Nuclear Information System (INIS)

Lewandowski, Jerome L.V.

2005-01-01

A new method for the solution of nonlinear dispersive partial differential equations is described. The marker method relies on the definition of a convective field associated with the underlying partial differential equation; the information about the approximate solution is associated with the response of an ensemble of markers to this convective field. Some key aspects of the method, such as the selection of the shape function and the initial loading, are discussed in some details

Primitive human hematopoietic cells give rise to differentially specified daughter cells upon their initial cell division.

NARCIS (Netherlands)

Giebel, B.; Zhang, T.; Beckmann, J.; Spanholtz, J.; Wernet, P.; Ho, A.; Punzel, M.

2006-01-01

It is often predicted that stem cells divide asymmetrically, creating a daughter cell that maintains the stem-cell capacity, and 1 daughter cell committed to differentiation. While asymmetric stem-cell divisions have been proven to occur in model organisms (eg, in Drosophila), it remains illusive

Which Spouse Initiates Marital Separation when There Are Children Involved?

Science.gov (United States)

Hewitt, Belinda

2009-01-01

This report examines whether the presence of children in marriage differentially influences the risk of wives or husbands initiating separation. The analytic sample consists of 9,118 first marriages from the Households, Income and Labour Dynamics in Australia survey (2001). Using event history and competing risks analysis, I find weak evidence…

The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila.

Science.gov (United States)

Liotta, David; Han, Jun; Elgar, Stuart; Garvey, Clare; Han, Zhe; Taylor, Michael V

2007-08-21

Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed.

Identification of Noncanonical Wnt Receptors Required for Wnt-3a-Induced Early Differentiation of Human Neural Stem Cells.

Science.gov (United States)

Bengoa-Vergniory, Nora; Gorroño-Etxebarria, Irantzu; López-Sánchez, Inmaculada; Marra, Michele; Di Chiaro, Pierluigi; Kypta, Robert

2017-10-01

Wnt proteins preferentially activate either β-catenin-dependent or β-catenin-independent signals, but the activity of a particular Wnt also depends on cellular context and receptor availability. We previously reported that Wnt-3a induces neural differentiation of human embryonic stem cell-derived neural stem cells (NSCs) in a β-catenin-independent manner by activating a signal involving JNK and the AP-1 family member ATF-2. Here, we report the results of a gene silencing approach to identify the Wnt receptors that mediate this response to Wnt-3a. Silencing of ROR2 increased neuronal differentiation, as measured by expression of the genes DCX, NEUROD1, and NGN1, suggesting ROR2 signals normally prevent differentiation. Silencing of the other Wnt receptors singly did not affect Wnt-3a-induced neuronal differentiation. However, pairwise silencing of ROR1 and FZD4 or FZD5 and of LRP6 and FZD4 or FZD5 inhibited neuronal differentiation, as detected by reductions in the expression of neuronal genes and immunocytochemical detection of DCX, NEUROD1 and DCX. Ectopic expression of these receptors in HEK 293 cells increased ATF2-dependent transcription. In addition, ROR1 coimmunoprecipitated with FZD4 and LRP6 in transfected HEK 293 cells and colocalized with FZD4 and with LRP6 at the cell surface of transfected L cells. Wnt-3a did not appear to affect these interactions but did alter the interactions between LRP6 and FZD4/5. Together, these observations highlight roles for ROR1, LRP6, FZD4, and FZD5 in neural stem cell differentiation and provide support for a model in which dynamic interactions among these receptors mediate Wnt-3a activation of ATF2 signaling.

Regulation of meiotic entry and gonadal sex differentiation in the human

DEFF Research Database (Denmark)

Jørgensen, Anne; Rajpert-De Meyts, Ewa

2014-01-01

Meiosis is a unique type of cell division that is performed only by germ cells to form haploid gametes. The switch from mitosis to meiosis exhibits a distinct sex-specific difference in timing, with female germ cells entering meiosis during fetal development and male germ cells at puberty when...... spermatogenesis is initiated. During early fetal development, bipotential primordial germ cells migrate to the forming gonad where they remain sexually indifferent until the sex-specific differentiation of germ cells is initiated by cues from the somatic cells. This irreversible step in gonadal sex...... in the context of fetal gonad development and germ cell differentiation, with emphasis on results obtained in humans. Furthermore, the consequences of dysregulated meiosis signaling in humans are briefly discussed in the context of selected pathologies, including testicular germ cell cancer and some forms...

An Efficient Numerical Approach for Solving Nonlinear Coupled Hyperbolic Partial Differential Equations with Nonlocal Conditions

Directory of Open Access Journals (Sweden)

A. H. Bhrawy

2014-01-01

Full Text Available One of the most important advantages of collocation method is the possibility of dealing with nonlinear partial differential equations (PDEs as well as PDEs with variable coefficients. A numerical solution based on a Jacobi collocation method is extended to solve nonlinear coupled hyperbolic PDEs with variable coefficients subject to initial-boundary nonlocal conservation conditions. This approach, based on Jacobi polynomials and Gauss-Lobatto quadrature integration, reduces solving the nonlinear coupled hyperbolic PDEs with variable coefficients to a system of nonlinear ordinary differential equation which is far easier to solve. In fact, we deal with initial-boundary coupled hyperbolic PDEs with variable coefficients as well as initial-nonlocal conditions. Using triangular, soliton, and exponential-triangular solutions as exact solutions, the obtained results show that the proposed numerical algorithm is efficient and very accurate.

Regulation of TFIIIB during F9 cell differentiation.

Science.gov (United States)

Athineos, Dimitris; Marshall, Lynne; White, Robert J

2010-03-12

Differentiation of F9 embryonal carcinoma (EC) cells into parietal endoderm (PE) provides a tractable model system for studying molecular events during early and inaccessible stages of murine development. PE formation is accompanied by extensive changes in gene expression both in vivo and in culture. One of the most dramatic is the ~10-fold decrease in transcriptional output by RNA polymerase (pol) III. This has been attributed to changes in activity of TFIIIB, a factor that is necessary and sufficient to recruit pol III to promoters. The goal of this study was to identify molecular changes that can account for the low activity of TFIIIB following F9 cell differentiation. Three essential subunits of TFIIIB decrease in abundance as F9 cells differentiate; these are Brf1 and Bdp1, which are pol III-specific, and TBP, which is also used by pols I and II. The decreased levels of Brf1 and Bdp1 proteins can be explained by reduced expression of the corresponding mRNAs. However, this is not the case for TBP, which is regulated post-transcriptionally. In proliferating cells, pol III transcription is stimulated by the proto-oncogene product c-Myc and the mitogen-activated protein kinase Erk, both of which bind to TFIIIB. However, c-Myc levels fall during differentiation and Erk becomes inactive through dephosphorylation. The diminished abundance of TFIIIB is therefore likely to be compounded by changes to these positive regulators that are required for its full activity. In addition, PE cells have elevated levels of the retinoblastoma protein RB, which is known to bind and repress TFIIIB. The low activity of TFIIIB in PE can be attributed to a combination of changes, any one of which could be sufficient to inhibit pol III transcription. Declining levels of essential TFIIIB subunits and of activators that are required for maximal TFIIIB activity are accompanied by an increase in a potent repressor of TFIIIB. These events provide fail-safe guarantees to ensure that pol III

Requirement of carbon dioxide for initial growth of facultative methylotroph, Acidomonas methanolica MB58.

Science.gov (United States)

Mitsui, Ryoji; Katayama, Hiroko; Tanaka, Mitsuo

2015-07-01

The facultative methylotrophic bacterium Acidomonas methanolica MB58 can utilize C1 compounds via the ribulose monophosphate pathway. A large gene cluster comprising three components related to C1 metabolism was found in the genome. From upstream, the first was an mxa cluster encoding proteins for oxidation of methanol to formaldehyde; the second was the rmp cluster encoding enzymes for formaldehyde fixation; and the third was the cbb gene cluster encoding proteins for carbon dioxide (CO2) fixation. Examination of CO2 requirements for growth of A. methanolica MB58 cells demonstrated that it did not grow on any carbon source under CO2-free conditions. Measurement of ribulose-1,5-bisphosphate carboxylase activity and RT-PCR analysis demonstrated enzymatic activity was detected in A. methanolica MB58 at growth phase, regardless of carbon sources. However, methanol dehydrogenase and 3-hexlose-6-phosphate synthase expression was regulated by methanol or formaldehyde; it were detected during growth and apparently differed from ribulose-1,5-bisphosphate carboxylase expression. These results suggested that A. methanolica MB58 may be initially dependent on autotrophic growth and that carbon assimilation was subsequently coupled with the ribulose monophosphate pathway at early- to mid-log phases during methylotrophic growth. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Differentiating Writing Instruction: Meeting the Diverse Needs of Authors in a Classroom

Science.gov (United States)

Shea, Mary

2015-01-01

This article outlines a rational for responsive, differentiated writing instruction that targets students' identified needs with respect to various dimensions of the writing process. Discussed is a cycle that requires ongoing assessment, instructional decision-making, responsive, differentiated instruction, guided practice, and assessment.…

Hippocalcin Is Required for Astrocytic Differentiation through Activation of Stat3 in Hippocampal Neural Precursor Cells.

Directory of Open Access Journals (Sweden)

Min-Jeong Kang

2016-10-01

Full Text Available Hippocalcin (Hpca is a neuronal calcium sensor protein expressed in the mammalian brain. However, its function in neural stem/precursor cells has not yet been studied. Here, we clarify the function of Hpca in astrocytic differentiation in hippocampal neural precursor cells (HNPCs. When we overexpressed Hpca in HNPCs in the presence or absence of bFGF, expression levels of nerve-growth factors such as neurotrophin-3 (NT-3, neurotrophin-4/5 (NT-4/5 and brain-derived neurotrophic factor (BDNF, together with the proneural basic helix loop helix (bHLH transcription factors neuroD and neurogenin 1 (ngn1, increased significantly. In addition, there was an increase in the number of cells expressing glial fibrillary acidic protein (GFAP, an astrocyte marker, and in dendrite outgrowth, indicating astrocytic differentiation of the HNPCs. Downregulation of Hpca by transfection with Hpca siRNA reduced expression of NT-3, NT-4/5, BDNF, neuroD and ngn1 as well as levels of GFAP protein. Furthermore, overexpression of Hpca increased the phosphorylation of STAT3 (Ser727, and this effect was abolished by treatment with a STAT3 inhibitor (S3I-201, suggesting that STAT3 (Ser727 activation is involved in Hpca-mediated astrocytic differentiation. As expected, treatment with Stat3 siRNA or STAT3 inhibitor caused a complete inhibition of astrogliogenesis induced by Hpca overexpression. Taken together, this is the first report to show that Hpca, acting through Stat3, has an important role in the expression of neurotrophins and proneural bHLH transcription factors, and that it is an essential regulator of astrocytic differentiation and dendrite outgrowth in HNPCs.

An Economy of Class Differential: Productivity in Composition Studies.

Science.gov (United States)

Vandenberg, Peter

By the late 19th century, the new universities in the United States had become so closely intertwined with the research imperative that their future depended on their position at the center of knowledge creation. The tension between the liberal arts college and the "modern" research university initiated a process of differentiation that…

Fault detection and diagnosis in nonlinear systems a differential and algebraic viewpoint

CERN Document Server

Martinez-Guerra, Rafael

2014-01-01

The high reliability required in industrial processes has created the necessity of detecting abnormal conditions, called faults, while processes are operating. The term fault generically refers to any type of process degradation, or degradation in equipment performance because of changes in the process's physical characteristics, process inputs or environmental conditions. This book is about the fundamentals of fault detection and diagnosis in a variety of nonlinear systems which are represented by ordinary differential equations. The fault detection problem is approached from a differential algebraic viewpoint, using residual generators based upon high-gain nonlinear auxiliary systems (‘observers’). A prominent role is played by the type of mathematical tools that will be used, requiring knowledge of differential algebra and differential equations. Specific theorems tailored to the needs of the problem-solving procedures are developed and proved. Applications to real-world problems, both with constant an...

Interactive differential equations modeling program

International Nuclear Information System (INIS)

Rust, B.W.; Mankin, J.B.

1976-01-01

Due to the recent emphasis on mathematical modeling, many ecologists are using mathematics and computers more than ever, and engineers, mathematicians and physical scientists are now included in ecological projects. However, the individual ecologist, with intuitive knowledge of the system, still requires the means to critically examine and adjust system models. An interactive program was developed with the primary goal of allowing an ecologist with minimal experience in either mathematics or computers to develop a system model. It has also been used successfully by systems ecologists, engineers, and mathematicians. This program was written in FORTRAN for the DEC PDP-10, a remote terminal system at Oak Ridge National Laboratory. However, with relatively minor modifications, it can be implemented on any remote terminal system with a FORTRAN IV compiler, or equivalent. This program may be used to simulate any phenomenon which can be described as a system of ordinary differential equations. The program allows the user to interactively change system parameters and/or initial conditions, to interactively select a set of variables to be plotted, and to model discontinuities in the state variables and/or their derivatives. One of the most useful features to the non-computer specialist is the ability to interactively address the system parameters by name and to interactively adjust their values between simulations. These and other features are described in greater detail

The inverse F-BAR domain protein srGAP2 acts through srGAP3 to modulate neuronal differentiation and neurite outgrowth of mouse neuroblastoma cells.

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Yue Ma

Full Text Available The inverse F-BAR (IF-BAR domain proteins srGAP1, srGAP2 and srGAP3 are implicated in neuronal development and may be linked to mental retardation, schizophrenia and seizure. A partially overlapping expression pattern and highly similar protein structures indicate a functional redundancy of srGAPs in neuronal development. Our previous study suggests that srGAP3 negatively regulates neuronal differentiation in a Rac1-dependent manner in mouse Neuro2a cells. Here we show that exogenously expressed srGAP1 and srGAP2 are sufficient to inhibit valporic acid (VPA-induced neurite initiation and growth in the mouse Neuro2a cells. While ectopic- or over-expression of RhoGAP-defective mutants, srGAP1(R542A and srGAP2(R527A exert a visible inhibitory effect on neuronal differentiation. Unexpectedly, knockdown of endogenous srGAP2 fails to facilitate the neuronal differentiation induced by VPA, but promotes neurite outgrowth of differentiated cells. All three IF-BAR domains from srGAP1-3 can induce filopodia formation in Neuro2a, but the isolated IF-BAR domain from srGAP2, not from srGAP1 and srGAP3, can promote VPA-induced neurite initiation and neuronal differentiation. We identify biochemical and functional interactions of the three srGAPs family members. We propose that srGAP3-Rac1 signaling may be required for the effect of srGAP1 and srGAP2 on attenuating neuronal differentiation. Furthermore, inhibition of Slit-Robo interaction can phenocopy a loss-of-function of srGAP3, indicating that srGAP3 may be dedicated to the Slit-Robo pathway. Our results demonstrate the interplay between srGAP1, srGAP2 and srGAP3 regulates neuronal differentiation and neurite outgrowth. These findings may provide us new insights into the possible roles of srGAPs in neuronal development and a potential mechanism for neurodevelopmental diseases.

Synchronization with propagation - The functional differential equations

Science.gov (United States)

Rǎsvan, Vladimir

2016-06-01

The structure represented by one or several oscillators couple to a one-dimensional transmission environment (e.g. a vibrating string in the mechanical case or a lossless transmission line in the electrical case) turned to be attractive for the research in the field of complex structures and/or complex behavior. This is due to the fact that such a structure represents some generalization of various interconnection modes with lumped parameters for the oscillators. On the other hand the lossless and distortionless propagation along transmission lines has generated several research in electrical, thermal, hydro and control engineering leading to the association of some functional differential equations to the basic initial boundary value problems. The present research is performed at the crossroad of the aforementioned directions. We shall associate to the starting models some functional differential equations - in most cases of neutral type - and make use of the general theorems for existence and stability of forced oscillations for functional differential equations. The challenges introduced by the analyzed problems for the general theory are emphasized, together with the implication of the results for various applications.

A New Method of High-Precision Positioning for an Indoor Pseudolite without Using the Known Point Initialization.

Science.gov (United States)

Zhao, Yinzhi; Zhang, Peng; Guo, Jiming; Li, Xin; Wang, Jinling; Yang, Fei; Wang, Xinzhe

2018-06-20

Due to the great influence of multipath effect, noise, clock and error on pseudorange, the carrier phase double difference equation is widely used in high-precision indoor pseudolite positioning. The initial position is determined mostly by the known point initialization (KPI) method, and then the ambiguities can be fixed with the LAMBDA method. In this paper, a new method without using the KPI to achieve high-precision indoor pseudolite positioning is proposed. The initial coordinates can be quickly obtained to meet the accuracy requirement of the indoor LAMBDA method. The detailed processes of the method follows: Aiming at the low-cost single-frequency pseudolite system, the static differential pseudolite system (DPL) method is used to obtain the low-accuracy positioning coordinates of the rover station quickly. Then, the ambiguity function method (AFM) is used to search for the coordinates in the corresponding epoch. The real coordinates obtained by AFM can meet the initial accuracy requirement of the LAMBDA method, so that the double difference carrier phase ambiguities can be correctly fixed. Following the above steps, high-precision indoor pseudolite positioning can be realized. Several experiments, including static and dynamic tests, are conducted to verify the feasibility of the new method. According to the results of the experiments, the initial coordinates with the accuracy of decimeter level through the DPL can be obtained. For the AFM part, both a one-meter search scope and two-centimeter or four-centimeter search steps are used to ensure the precision at the centimeter level and high search efficiency. After dealing with the problem of multiple peaks caused by the ambiguity cosine function, the coordinate information of the maximum ambiguity function value (AFV) is taken as the initial value of the LAMBDA, and the ambiguities can be fixed quickly. The new method provides accuracies at the centimeter level for dynamic experiments and at the millimeter

Deterministic Brownian motion generated from differential delay equations.

Science.gov (United States)

Lei, Jinzhi; Mackey, Michael C

2011-10-01

This paper addresses the question of how Brownian-like motion can arise from the solution of a deterministic differential delay equation. To study this we analytically study the bifurcation properties of an apparently simple differential delay equation and then numerically investigate the probabilistic properties of chaotic solutions of the same equation. Our results show that solutions of the deterministic equation with randomly selected initial conditions display a Gaussian-like density for long time, but the densities are supported on an interval of finite measure. Using these chaotic solutions as velocities, we are able to produce Brownian-like motions, which show statistical properties akin to those of a classical Brownian motion over both short and long time scales. Several conjectures are formulated for the probabilistic properties of the solution of the differential delay equation. Numerical studies suggest that these conjectures could be "universal" for similar types of "chaotic" dynamics, but we have been unable to prove this.

SciCADE 95: International conference on scientific computation and differential equations

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-31

This report consists of abstracts from the conference. Topics include algorithms, computer codes, and numerical solutions for differential equations. Linear and nonlinear as well as boundary-value and initial-value problems are covered. Various applications of these problems are also included.

Influence of initial state distortion in ion-atom collisions

Energy Technology Data Exchange (ETDEWEB)

Ciappina, M F [CONICET and Departamento de FIsica, Universidad Nacional del Sur, 8000 BahIa Blanca (Argentina); Cravero, W R [CONICET and Departamento de FIsica, Universidad Nacional del Sur, 8000 BahIa Blanca (Argentina); Garibotti, C R [CONICET and Division Colisiones Atomicas, Centro Atomico Bariloche, 8400 Bariloche (Argentina)

2004-05-28

We have studied the influence of initial state distortion in a single ionization by ion impact. We have taken a continuum distorted wave type distortion and by taking up to the first order in its asymptotic series expansion we build an eikonal-spherical distortion. In this way the influence of each term in the transition amplitude can be stated. This approximation can be considered an intermediate one between the eikonal initial state and the continuum distorted wave approaches for initial state distortion. We have computed doubly differential cross sections for helium ionization by protons and highly charged ions at high and intermediate impact energy. We have also discussed the contribution of the different terms in electron energy spectra, specially in the vicinity of ECC peak. Very good agreement is found with the available experimental data.

Influence of initial state distortion in ion-atom collisions

International Nuclear Information System (INIS)

Ciappina, M F; Cravero, W R; Garibotti, C R

2004-01-01

We have studied the influence of initial state distortion in a single ionization by ion impact. We have taken a continuum distorted wave type distortion and by taking up to the first order in its asymptotic series expansion we build an eikonal-spherical distortion. In this way the influence of each term in the transition amplitude can be stated. This approximation can be considered an intermediate one between the eikonal initial state and the continuum distorted wave approaches for initial state distortion. We have computed doubly differential cross sections for helium ionization by protons and highly charged ions at high and intermediate impact energy. We have also discussed the contribution of the different terms in electron energy spectra, specially in the vicinity of ECC peak. Very good agreement is found with the available experimental data

Optimal control of motorsport differentials

Science.gov (United States)

Tremlett, A. J.; Massaro, M.; Purdy, D. J.; Velenis, E.; Assadian, F.; Moore, A. P.; Halley, M.

2015-12-01

Modern motorsport limited slip differentials (LSD) have evolved to become highly adjustable, allowing the torque bias that they generate to be tuned in the corner entry, apex and corner exit phases of typical on-track manoeuvres. The task of finding the optimal torque bias profile under such varied vehicle conditions is complex. This paper presents a nonlinear optimal control method which is used to find the minimum time optimal torque bias profile through a lane change manoeuvre. The results are compared to traditional open and fully locked differential strategies, in addition to considering related vehicle stability and agility metrics. An investigation into how the optimal torque bias profile changes with reduced track-tyre friction is also included in the analysis. The optimal LSD profile was shown to give a performance gain over its locked differential counterpart in key areas of the manoeuvre where a quick direction change is required. The methodology proposed can be used to find both optimal passive LSD characteristics and as the basis of a semi-active LSD control algorithm.

Ordinary differential equations

CERN Document Server

Cox, William

1995-01-01

Building on introductory calculus courses, this text provides a sound foundation in the underlying principles of ordinary differential equations. Important concepts, including uniqueness and existence theorems, are worked through in detail and the student is encouraged to develop much of the routine material themselves, thus helping to ensure a solid understanding of the fundamentals required.The wide use of exercises, problems and self-assessment questions helps to promote a deeper understanding of the material and it is developed in such a way that it lays the groundwork for further

OPTIMIZING LENVATINIB THERAPY IN PATIENTS WITH METASTATIC RADIOACTIVE IODINE-RESISTANT DIFFERENTIATED THYROID CANCERS.

Science.gov (United States)

Jasim, Sina; Iniguez-Ariza, Nicole M; Hilger, Crystal R; Chintakuntlawar, Ashish V; Ryder, Mabel M; Morris, John C; Bible, Keith C

2017-10-01

Lenvatinib is approved for use in advanced radioactive iodine-resistant differentiated thyroid cancers (RAIR-DTCs). Its efficacy is indisputable, but toxicities are great, creating daunting challenges for patients and providers. Few data regarding early adverse events and impact on quality of life (QOL) exist; we sought to clarify these issues by analyzing our initial postapproval lenvatinib experience. Standardized patient education was implemented, providing detailed instructions and expert provider contacts to facilitate timely reporting of toxicities and guide responsive actions. Early adverse events, QOL outcomes, and response data from 25 consecutively treated DTC patients (02/2015 and 05/2016) were retrospectively analyzed. The median age was 55 years (range 27-81); 52% were female. Fourteen (56%) were on antihypertensive medication(s) at baseline. Most patients (21/25, 84%) developed adverse events during the first month of therapy. Hypertension arose in 16/25 (64%), requiring antihypertensive dose adjustment/addition in 6 (24%)/12 (48%) patients, respectively, during the first month of therapy. Dose reduction was required in 11 (44%) due to multiple adverse events; the median time to first dose reduction was 33 days (range 11-84); 8 (32%) required multiple dose reductions. Therapy interruption >3 weeks occurred in 4 (16%). The median change in patient-reported fatigue score was +2 (worsening, range -2 to +10, P<.007; 0-10 scales), but the median QOL change was 0 (range +4 to -9, P = .57). The mean duration of lenvatinib therapy was 6.5 months (range 1-12); median overall and progression-free survival have not yet been reached. Lenvatinib was discontinued in 7 (28%) patients; among 20 patients with available RECIST (Response Evaluation Criteria In Solid Tumors) measurements, 10 (50%) achieved partial response. Lenvatinib has promising efficacy in RAIR-DTC, but toxicities require frequent early interventions. QOL can be maintained on lenvatinib therapy. DTC

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons

Directory of Open Access Journals (Sweden)

Vitor Fortuna

2015-06-01

Full Text Available The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs develop in close proximity to the dorsal aorta (DA and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA differentiation of SN precursors temporally coincides with vascular mural cell (VMC recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation.

Canada's family violence initiative: partnerships

Directory of Open Access Journals (Sweden)

Elaine Scott

1994-01-01

Full Text Available Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and development of projects. Activities funded by the seven federal departments and agencies involved in the Initiative emphasize partnerships with the professional, voluntary, corporate, non-government and government sectors.

Singular Cauchy Initial Value Problem for Certain Classes of Integro-Differential Equations

Directory of Open Access Journals (Sweden)

Zdeněk Šmarda

2010-01-01

Full Text Available The existence and uniqueness of solutions and asymptotic estimate of solution formulas are studied for the following initial value problem: g(ty′(t=ay(t[1+f(t,y(t,∫0+tK(t,s,y(t,y(sds], y(0+=0, t∈(0,t0], where a>0 is a constant and t0>0. An approach which combines topological method of T. Ważewski and Schauder's fixed point theorem is used.

Differential cross sections for single ionization of H2 by 75keV proton impact

International Nuclear Information System (INIS)

Chowdhury, U; Schulz, M; Madison, D H

2012-01-01

We have calculated Triply differential cross sections (TDCS) and doubly differential cross sections (DDCS) for single ionization of H 2 by 75 keV proton impact using the molecular 3 body distorted wave Eikonal initial state (M3DW-EIS) approach. Previously published measured DDCS-P (differential in the projectile scattering angle and integrated over the ejected electron angles) found pronounced structures at relatively large angles which were interpreted as an interference resulting from the two-centered potential of the molecule.

Canada's family violence initiative: partnerships

OpenAIRE

Scott,Elaine

1994-01-01

Under Canada's four-year, $136 million Family Violence Initiative, the federal government is calling upon all Canadians to work in partnerships towards the elimination of family violence - child abuse, violence against women, and elder (senior) abuse. Family violence is a complex problem and requires the efforts of all Canadians to resolve it. One of the key themes of the Initiative - a multidisciplinary approach to the problem of family violence - is reflected in the selection and developmen...

Cosmological constant and general isocurvature initial conditions

International Nuclear Information System (INIS)

Trotta, R.; Riazuelo, A.; Durrer, R.

2003-01-01

We investigate in detail the question of whether a nonvanishing cosmological constant is required by the present-day cosmic microwave background and large scale structure data when general isocurvature initial conditions are taken into account. We also discuss the differences between the usual Bayesian and the frequentist approaches in data analysis. We show that the Cosmic Background Explorer (COBE)-normalized matter power spectrum is dominated by the adiabatic mode and therefore breaks the degeneracy between initial conditions which is present in the cosmic microwave background anisotropies. We find that in a flat universe the Bayesian analysis requires Ω Λ =e0 to more than 3σ, while in the frequentist approach Ω Λ =0 is still within 3σ for a value of h≤0.48. Both conclusions hold regardless of the initial conditions

Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells

Energy Technology Data Exchange (ETDEWEB)

Zhou, Haibin; Shang, Linshan; Li, Xi; Zhang, Xiyu; Gao, Guimin; Guo, Chenhong; Chen, Bingxi; Liu, Qiji [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Gong, Yaoqin, E-mail: yxg8@sdu.edu.cn [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Shao, Changshun, E-mail: shao@biology.rutgers.edu [Key Laboratory of Experimental Teratology, MOE, Institute of Molecular Medicine and Genetics, Shandong University, 44 Wen Hua Xi Lu, Jinan, Shandong 250012 (China); Department of Genetics, Rutgers University, Piscataway, NJ 08854 (United States)

2009-10-15

Resveratrol has been shown to possess many health-benefiting effects, including the promotion of bone formation. In this report we investigated the mechanism by which resveratrol promotes osteoblastic differentiation from pluripotent mesenchymal cells. Since Wnt signaling is well documented to induce osteoblastogenesis and bone formation, we characterized the factors involved in Wnt signaling in response to resveratrol treatment. Resveratrol treatment of mesenchymal cells led to an increase in stabilization and nuclear accumulation of {beta}-catenin dose-dependently and time-dependently. As a consequence of the increased nuclear accumulation of {beta}-catenin, the ability to activate transcription of {beta}-catenin-TCF/LEF target genes that are required for osteoblastic differentiation was upregulated. However, resveratrol did not affect the initial step of the Wnt signaling pathway, as resveratrol was as effective in upregulating the activity of {beta}-catenin in cells in which Lrp5 was knocked down as in control cells. In addition, while conditioned medium enriched in Wnt signaling antagonist Dkk1 was able to inhibit Wnt3a-induced {beta}-catenin upregulation, this inhibitory effect can be abolished in resveratrol-treated cells. Furthermore, we showed that the level of glycogen synthase kinase 3{beta} (GSK-3{beta}), which phosphorylates and destabilizes {beta}-catenin, was reduced in response to resveratrol treatment. The phosphorylation of GSK-3{beta} requires extracellular signal-regulated kinase (ERK)1/2. Together, our data indicate that resveratrol promotes osteoblastogenesis and bone formation by augmenting Wnt signaling.

Resveratrol augments the canonical Wnt signaling pathway in promoting osteoblastic differentiation of multipotent mesenchymal cells

International Nuclear Information System (INIS)

Zhou, Haibin; Shang, Linshan; Li, Xi; Zhang, Xiyu; Gao, Guimin; Guo, Chenhong; Chen, Bingxi; Liu, Qiji; Gong, Yaoqin; Shao, Changshun

2009-01-01

Resveratrol has been shown to possess many health-benefiting effects, including the promotion of bone formation. In this report we investigated the mechanism by which resveratrol promotes osteoblastic differentiation from pluripotent mesenchymal cells. Since Wnt signaling is well documented to induce osteoblastogenesis and bone formation, we characterized the factors involved in Wnt signaling in response to resveratrol treatment. Resveratrol treatment of mesenchymal cells led to an increase in stabilization and nuclear accumulation of β-catenin dose-dependently and time-dependently. As a consequence of the increased nuclear accumulation of β-catenin, the ability to activate transcription of β-catenin-TCF/LEF target genes that are required for osteoblastic differentiation was upregulated. However, resveratrol did not affect the initial step of the Wnt signaling pathway, as resveratrol was as effective in upregulating the activity of β-catenin in cells in which Lrp5 was knocked down as in control cells. In addition, while conditioned medium enriched in Wnt signaling antagonist Dkk1 was able to inhibit Wnt3a-induced β-catenin upregulation, this inhibitory effect can be abolished in resveratrol-treated cells. Furthermore, we showed that the level of glycogen synthase kinase 3β (GSK-3β), which phosphorylates and destabilizes β-catenin, was reduced in response to resveratrol treatment. The phosphorylation of GSK-3β requires extracellular signal-regulated kinase (ERK)1/2. Together, our data indicate that resveratrol promotes osteoblastogenesis and bone formation by augmenting Wnt signaling.

OPTIMAL ESTIMATES FOR THE SEMIDISCRETE GALERKIN METHOD APPLIED TO PARABOLIC INTEGRO-DIFFERENTIAL EQUATIONS WITH NONSMOOTH DATA

KAUST Repository

GOSWAMI, DEEPJYOTI; PANI, AMIYA K.; YADAV, SANGITA

2014-01-01

AWe propose and analyse an alternate approach to a priori error estimates for the semidiscrete Galerkin approximation to a time-dependent parabolic integro-differential equation with nonsmooth initial data. The method is based on energy arguments combined with repeated use of time integration, but without using parabolic-type duality techniques. An optimal L2-error estimate is derived for the semidiscrete approximation when the initial data is in L2. A superconvergence result is obtained and then used to prove a maximum norm estimate for parabolic integro-differential equations defined on a two-dimensional bounded domain. © 2014 Australian Mathematical Society.

Inductive differentiation of two neural lineages reconstituted in a microculture system from Xenopus early gastrula cells.

Science.gov (United States)

Mitani, S; Okamoto, H

1991-05-01

Neural induction of ectoderm cells has been reconstituted and examined in a microculture system derived from dissociated early gastrula cells of Xenopus laevis. We have used monoclonal antibodies as specific markers to monitor cellular differentiation from three distinct ectoderm lineages in culture (N1 for CNS neurons from neural tube, Me1 for melanophores from neural crest and E3 for skin epidermal cells from epidermal lineages). CNS neurons and melanophores differentiate when deep layer cells of the ventral ectoderm (VE, prospective epidermis region; 150 cells/culture) and an appropriate region of the marginal zone (MZ, prospective mesoderm region; 5-150 cells/culture) are co-cultured, but not in cultures of either cell type on their own; VE cells cultured alone yield epidermal cells as we have previously reported. The extent of inductive neural differentiation in the co-culture system strongly depends on the origin and number of MZ cells initially added to culture wells. The potency to induce CNS neurons is highest for dorsal MZ cells and sharply decreases as more ventrally located cells are used. The same dorsoventral distribution of potency is seen in the ability of MZ cells to inhibit epidermal differentiation. In contrast, the ability of MZ cells to induce melanophores shows the reverse polarity, ventral to dorsal. These data indicate that separate developmental mechanisms are used for the induction of neural tube and neural crest lineages. Co-differentiation of CNS neurons or melanophores with epidermal cells can be obtained in a single well of co-cultures of VE cells (150) and a wide range of numbers of MZ cells (5 to 100). Further, reproducible differentiation of both neural lineages requires intimate association between cells from the two gastrula regions; virtually no differentiation is obtained when cells from the VE and MZ are separated in a culture well. These results indicate that the inducing signals from MZ cells for both neural tube and neural

Analysis of Nonlinear Duopoly Games with Product Differentiation: Stability, Global Dynamics, and Control

Directory of Open Access Journals (Sweden)

S. S. Askar

2017-01-01

Full Text Available Many researchers have used quadratic utility function to study its influences on economic games with product differentiation. Such games include Cournot, Bertrand, and a mixed-type game called Cournot-Bertrand. Within this paper, a cubic utility function that is derived from a constant elasticity of substitution production function (CES is introduced. This cubic function is more desirable than the quadratic one besides its amenability to efficiency analysis. Based on that utility a two-dimensional Cournot duopoly game with horizontal product differentiation is modeled using a discrete time scale. Two different types of games are studied in this paper. In the first game, firms are updating their output production using the traditional bounded rationality approach. In the second game, firms adopt Puu’s mechanism to update their productions. Puu’s mechanism does not require any information about the profit function; instead it needs both firms to know their production and their profits in the past time periods. In both scenarios, an explicit form for the Nash equilibrium point is obtained under certain conditions. The stability analysis of Nash point is considered. Furthermore, some numerical simulations are carried out to confirm the chaotic behavior of Nash equilibrium point. This analysis includes bifurcation, attractor, maximum Lyapunov exponent, and sensitivity to initial conditions.

A novel crosstalk between Alk7 and cGMP signaling differentially regulates brown adipocyte function

Directory of Open Access Journals (Sweden)

Aileen Balkow

2015-08-01

Conclusions: We found a so far unknown crosstalk between cGMP and Alk7 signaling pathways. Tight regulation of Alk7 is required for efficient differentiation of brown adipocytes. Alk7 has differential effects on adipogenic differentiation and the development of the thermogenic program in brown adipocytes.

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

Science.gov (United States)

Yüksel, Melih; Power, Jeffrey J; Ribbe, Jan; Volkmann, Thorsten; Maier, Berenike

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off.

A first course in differential equations

CERN Document Server

Logan, J David

2015-01-01

The third edition of this concise, popular textbook on elementary differential equations gives instructors an alternative to the many voluminous texts on the market. It presents a thorough treatment of the standard topics in an accessible, easy-to-read, format. The overarching perspective of the text conveys that differential equations are about applications. This book illuminates the mathematical theory in the text with a wide variety of applications that will appeal to students in physics, engineering, the biosciences, economics and mathematics. Instructors are likely to find that the first four or five chapters are suitable for a first course in the subject. This edition contains a healthy increase over earlier editions in the number of worked examples and exercises, particularly those routine in nature. Two appendices include a review with practice problems, and a MATLAB® supplement that gives basic codes and commands for solving differential equations. MATLAB® is not required; students are encouraged t...

Successive substitution one-leg hybrid P-stable LMM for initial value ...

African Journals Online (AJOL)

This paper derives P-stable successive substitution one-leg hybrid linear multistep methods for the numerical solution of second order initial value problems in ordinary differential equations without explicit first order derivative. The methods are demonstrated by a numerical example also considered by Fatunla, et al (1997) ...

Gaseous detonation initiation via wave implosion

Science.gov (United States)

Jackson, Scott Irving

Efficient detonation initiation is a topic of intense interest to designers of pulse detonation engines. This experimental work is the first to detonate propane-air mixtures with an imploding detonation wave and to detonate a gas mixture with a non-reflected, imploding shock. In order to do this, a unique device has been developed that is capable of generating an imploding toroidal detonation wave inside of a tube from a single ignition point without any obstruction to the tube flow path. As part of this study, an initiator that creates a large-aspect-ratio planar detonation wave in gas-phase explosive from a single ignition point has also been developed. The effectiveness of our initiation devices has been evaluated. The minimum energy required by the imploding shock for initiation was determined to scale linearly with the induction zone length, indicating the presence of a planar initiation mode. The imploding toroidal detonation initiator was found to be more effective at detonation initiation than the imploding shock initiator, using a comparable energy input to that of current initiator tubes.

Asymptotics for inhomogeneous Dirichlet initial-boundary value problem for the nonlinear Schrödinger equation

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Kaikina, Elena I., E-mail: ekaikina@matmor.unam.mx [Centro de Ciencias Matemáticas, UNAM Campus Morelia, AP 61-3 (Xangari), Morelia CP 58089, Michoacán (Mexico)

2013-11-15

We consider the inhomogeneous Dirichlet initial-boundary value problem for the nonlinear Schrödinger equation, formulated on a half-line. We study traditionally important problems of the theory of nonlinear partial differential equations, such as global in time existence of solutions to the initial-boundary value problem and the asymptotic behavior of solutions for large time.

Asymptotics for inhomogeneous Dirichlet initial-boundary value problem for the nonlinear Schrödinger equation

International Nuclear Information System (INIS)

Kaikina, Elena I.

2013-01-01

We consider the inhomogeneous Dirichlet initial-boundary value problem for the nonlinear Schrödinger equation, formulated on a half-line. We study traditionally important problems of the theory of nonlinear partial differential equations, such as global in time existence of solutions to the initial-boundary value problem and the asymptotic behavior of solutions for large time

Multiple-Symbol Differential Detection Of MPSK

Science.gov (United States)

Divsalar, Dariush; Simon, Marvin K.

1991-01-01

Multiple-symbol differential detection proposed for reception of radio-frequency signals modulated by mutliple-phase-shift keying (MPSK). Offers advantage of less complexity in not requiring equipment to acquire and track carrier signal. Performance approaches that of ideal coherent detection. Applicable to coded as well as uncoded MPSK, and to other forms of modulation.

Schisandrae fructus enhances myogenic differentiation and inhibits atrophy through protein synthesis in human myotubes

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Kim CH

2016-05-01

Full Text Available Cy Hyun Kim,1,2,* Jin-Hong Shin,1,3,* Sung Jun Hwang,1,2 Yung Hyun Choi,4 Dae-Seong Kim,1,3 Cheol Min Kim2,51Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, 2Center for Anti-Aging Industry, Pusan National University, Busan, 3Department of Neurology, Pusan National University Yangsan Hospital, Yangsan, 4Department of Biochemistry, Dong-eui University College of Korean Medicine, Busan, 5Department of Biomedical Informatics, Pusan National University School of Medicine, Yangsan, Republic of Korea*These authors contributed equally to this work Abstract: Schisandrae fructus (SF has recently been reported to increase skeletal muscle mass and inhibit atrophy in mice. We investigated the effect of SF extract on human myotube differentiation and its acting pathway. Various concentrations (0.1–10 µg/mL of SF extract were applied on human skeletal muscle cells in vitro. Myotube area and fusion index were measured to quantify myotube differentiation. The maximum effect was observed at 0.5 µg/mL of SF extract, enhancing differentiation up to 1.4-fold in fusion index and 1.6-fold in myotube area at 8 days after induction of differentiation compared to control. Phosphorylation of eukaryotic translation initiation factor 4E-binding protein 1 and 70 kDa ribosomal protein S6 kinase, which initiate translation as downstream of mammalian target of rapamycin pathway, was upregulated in early phases of differentiation after SF treatment. SF also attenuated dexamethasone-induced atrophy. In conclusion, we show that SF augments myogenic differentiation and attenuates atrophy by increasing protein synthesis through mammalian target of rapamycin/70 kDa ribosomal protein S6 kinase and eukaryotic translation initiation factor 4E-binding protein 1 signaling pathway in human myotubes. SF can be a useful natural dietary supplement in increasing skeletal muscle mass, especially in the aged

A Stochastic Differential Equation Model for the Spread of HIV amongst People Who Inject Drugs

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Yanfeng Liang

2016-01-01

Full Text Available We introduce stochasticity into the deterministic differential equation model for the spread of HIV amongst people who inject drugs (PWIDs studied by Greenhalgh and Hay (1997. This was based on the original model constructed by Kaplan (1989 which analyses the behaviour of HIV/AIDS amongst a population of PWIDs. We derive a stochastic differential equation (SDE for the fraction of PWIDs who are infected with HIV at time. The stochasticity is introduced using the well-known standard technique of parameter perturbation. We first prove that the resulting SDE for the fraction of infected PWIDs has a unique solution in (0, 1 provided that some infected PWIDs are initially present and next construct the conditions required for extinction and persistence. Furthermore, we show that there exists a stationary distribution for the persistence case. Simulations using realistic parameter values are then constructed to illustrate and support our theoretical results. Our results provide new insight into the spread of HIV amongst PWIDs. The results show that the introduction of stochastic noise into a model for the spread of HIV amongst PWIDs can cause the disease to die out in scenarios where deterministic models predict disease persistence.

A Stochastic Differential Equation Model for the Spread of HIV amongst People Who Inject Drugs.

Science.gov (United States)

Liang, Yanfeng; Greenhalgh, David; Mao, Xuerong

2016-01-01

We introduce stochasticity into the deterministic differential equation model for the spread of HIV amongst people who inject drugs (PWIDs) studied by Greenhalgh and Hay (1997). This was based on the original model constructed by Kaplan (1989) which analyses the behaviour of HIV/AIDS amongst a population of PWIDs. We derive a stochastic differential equation (SDE) for the fraction of PWIDs who are infected with HIV at time. The stochasticity is introduced using the well-known standard technique of parameter perturbation. We first prove that the resulting SDE for the fraction of infected PWIDs has a unique solution in (0, 1) provided that some infected PWIDs are initially present and next construct the conditions required for extinction and persistence. Furthermore, we show that there exists a stationary distribution for the persistence case. Simulations using realistic parameter values are then constructed to illustrate and support our theoretical results. Our results provide new insight into the spread of HIV amongst PWIDs. The results show that the introduction of stochastic noise into a model for the spread of HIV amongst PWIDs can cause the disease to die out in scenarios where deterministic models predict disease persistence.

Difference in the wind speeds required for initiation versus continuation of sand transport on mars: implications for dunes and dust storms.

Science.gov (United States)

Kok, Jasper F

2010-02-19

Much of the surface of Mars is covered by dunes, ripples, and other features formed by the blowing of sand by wind, known as saltation. In addition, saltation loads the atmosphere with dust aerosols, which dominate the Martian climate. We show here that saltation can be maintained on Mars by wind speeds an order of magnitude less than required to initiate it. We further show that this hysteresis effect causes saltation to occur for much lower wind speeds than previously thought. These findings have important implications for the formation of dust storms, sand dunes, and ripples on Mars.

Adams Predictor-Corrector Systems for Solving Fuzzy Differential Equations

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Dequan Shang

2013-01-01

Full Text Available A predictor-corrector algorithm and an improved predictor-corrector (IPC algorithm based on Adams method are proposed to solve first-order differential equations with fuzzy initial condition. These algorithms are generated by updating the Adams predictor-corrector method and their convergence is also analyzed. Finally, the proposed methods are illustrated by solving an example.

Periodicity computation of generalized mathematical biology problems involving delay differential equations.

Science.gov (United States)

Jasim Mohammed, M; Ibrahim, Rabha W; Ahmad, M Z

2017-03-01

In this paper, we consider a low initial population model. Our aim is to study the periodicity computation of this model by using neutral differential equations, which are recognized in various studies including biology. We generalize the neutral Rayleigh equation for the third-order by exploiting the model of fractional calculus, in particular the Riemann-Liouville differential operator. We establish the existence and uniqueness of a periodic computational outcome. The technique depends on the continuation theorem of the coincidence degree theory. Besides, an example is presented to demonstrate the finding.

Greenland Regional and Ice Sheet-wide Geometry Sensitivity to Boundary and Initial conditions

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Logan, L. C.; Narayanan, S. H. K.; Greve, R.; Heimbach, P.

2017-12-01

Ice sheet and glacier model outputs require inputs from uncertainly known initial and boundary conditions, and other parameters. Conservation and constitutive equations formalize the relationship between model inputs and outputs, and the sensitivity of model-derived quantities of interest (e.g., ice sheet volume above floatation) to model variables can be obtained via the adjoint model of an ice sheet. We show how one particular ice sheet model, SICOPOLIS (SImulation COde for POLythermal Ice Sheets), depends on these inputs through comprehensive adjoint-based sensitivity analyses. SICOPOLIS discretizes the shallow-ice and shallow-shelf approximations for ice flow, and is well-suited for paleo-studies of Greenland and Antarctica, among other computational domains. The adjoint model of SICOPOLIS was developed via algorithmic differentiation, facilitated by the source transformation tool OpenAD (developed at Argonne National Lab). While model sensitivity to various inputs can be computed by costly methods involving input perturbation simulations, the time-dependent adjoint model of SICOPOLIS delivers model sensitivities to initial and boundary conditions throughout time at lower cost. Here, we explore both the sensitivities of the Greenland Ice Sheet's entire and regional volumes to: initial ice thickness, precipitation, basal sliding, and geothermal flux over the Holocene epoch. Sensitivity studies such as described here are now accessible to the modeling community, based on the latest version of SICOPOLIS that has been adapted for OpenAD to generate correct and efficient adjoint code.

14 CFR 302.310 - Exemptions on the Department's initiative.

Science.gov (United States)

2010-01-01

... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Exemptions on the Department's initiative... and Certain Other Proceedings § 302.310 Exemptions on the Department's initiative. The Department may grant exemptions on its own initiative when it finds that such exemptions are required by the...

Differentiated protection services with failure probability guarantee for workflow-based applications

Science.gov (United States)

Zhong, Yaoquan; Guo, Wei; Jin, Yaohui; Sun, Weiqiang; Hu, Weisheng

2010-12-01

A cost-effective and service-differentiated provisioning strategy is very desirable to service providers so that they can offer users satisfactory services, while optimizing network resource allocation. Providing differentiated protection services to connections for surviving link failure has been extensively studied in recent years. However, the differentiated protection services for workflow-based applications, which consist of many interdependent tasks, have scarcely been studied. This paper investigates the problem of providing differentiated services for workflow-based applications in optical grid. In this paper, we develop three differentiated protection services provisioning strategies which can provide security level guarantee and network-resource optimization for workflow-based applications. The simulation demonstrates that these heuristic algorithms provide protection cost-effectively while satisfying the applications' failure probability requirements.

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

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Fortuna, Vitor; Pardanaud, Luc; Brunet, Isabelle; Ola, Roxana; Ristori, Emma; Santoro, Massimo M; Nicoli, Stefania; Eichmann, Anne

2015-06-23

The sympathetic nervous system controls smooth muscle tone and heart rate in the cardiovascular system. Postganglionic sympathetic neurons (SNs) develop in close proximity to the dorsal aorta (DA) and innervate visceral smooth muscle targets. Here, we use the zebrafish embryo to ask whether the DA is required for SN development. We show that noradrenergic (NA) differentiation of SN precursors temporally coincides with vascular mural cell (VMC) recruitment to the DA and vascular maturation. Blocking vascular maturation inhibits VMC recruitment and blocks NA differentiation of SN precursors. Inhibition of platelet-derived growth factor receptor (PDGFR) signaling prevents VMC differentiation and also blocks NA differentiation of SN precursors. NA differentiation is normal in cloche mutants that are devoid of endothelial cells but have VMCs. Thus, PDGFR-mediated mural cell recruitment mediates neurovascular interactions between the aorta and sympathetic precursors and promotes their noradrenergic differentiation. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

Science.gov (United States)

Spooner, B. S.; Hardman, P.; Paulsen, A.

1994-01-01

Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

A call for differentiated approaches to delivering HIV services to key populations.

Science.gov (United States)

Macdonald, Virginia; Verster, Annette; Baggaley, Rachel

2017-07-21

Key populations (KPs) are disproportionally affected by HIV and have low rates of access to HIV testing and treatment services compared to the broader population. WHO promotes the use of differentiated approaches for reaching and recruiting KP into the HIV services continuum. These approaches may help increase access to KPs who are often criminalized or stigmatized. By catering to the specific needs of each KP individual, differentiated approaches may increase service acceptability, quality and coverage, reduce costs and support KP members in leading the HIV response among their communities. WHO recommends the implementation of community-based and lay provider administered HIV testing services. Together, these approaches reduce barriers and costs associated with other testing strategies, allow greater ownership in HIV programmes for KP members and reach more people than do facility-based services. Despite this evidence availability and support for them is limited. Peer-driven interventions have been shown to be effective in engaging, recruiting and supporting clients. Some programmes employ HIV-positive or non-PLHIV "peer navigators" and other staff to provide case management, enrolment and/or re-enrolment in care and treatment services. However, a better understanding of the impact, cost effectiveness and potential burden on peer volunteers is required. Task shifting and non-facility-based service locations for antiretroviral therapy (ART) initiation and maintenance and antiretroviral (ARV) distribution are recommended in both the consolidated HIV treatment and KP guidelines of WHO. These approaches are accepted in generalized epidemics and for the general population where successful models exist; however, few organizations provide or initiate ART at KP community-based services. The application of a differentiated service approach for KP could increase the number of people who know their status and receive effective and sustained prevention and treatment for HIV

Calculus of tensors and differential forms

CERN Document Server

Sinha, Rajnikant

2014-01-01

Calculus of tensors and differential forms is an introductory-level textbook. Through this book, students will familiarize themselves with tools they need in order to use for further study on general relativity and research, such as affine tensors, tensor calculus on manifolds, relative tensors, Lie derivatives, wedge products, differential forms, and Stokes' theorem. The treatment is concrete and in detail, so that abstract concepts do not deter even physics and engineering students. This self contained book requires undergraduate-level calculus of several variables and linear algebra as prerequisite. Fubini's theorem in real analysis, to be used in Stokes' theorem, has been proved earlier than Stokes' theorem so that students don't have to search elsewhere.

Conversational assessment in memory clinic encounters: interactional profiling for differentiating dementia from functional memory disorders.

Science.gov (United States)

Jones, Danielle; Drew, Paul; Elsey, Christopher; Blackburn, Daniel; Wakefield, Sarah; Harkness, Kirsty; Reuber, Markus

2016-01-01

In the UK dementia is under-diagnosed, there is limited access to specialist memory clinics, and many of the patients referred to such clinics are ultimately found to have functional (non-progressive) memory disorders (FMD), rather than a neurodegenerative disorder. Government initiatives on 'timely diagnosis' aim to improve the rate and quality of diagnosis for those with dementia. This study seeks to improve the screening and diagnostic process by analysing communication between clinicians and patients during initial specialist clinic visits. Establishing differential conversational profiles could help the timely differential diagnosis of memory complaints. This study is based on video- and audio recordings of 25 initial consultations between neurologists and patients referred to a UK memory clinic. Conversation analysis was used to explore recurrent communicative practices associated with each diagnostic group. Two discrete conversational profiles began to emerge, to help differentiate between patients with dementia and functional memory complaints, based on (1) whether the patient is able to answer questions about personal information; (2) whether they can display working memory in interaction; (3) whether they are able to respond to compound questions; (4) the time taken to respond to questions; and (5) the level of detail they offer when providing an account of their memory failure experiences. The distinctive conversational profiles observed in patients with functional memory complaints on the one hand and neurodegenerative memory conditions on the other suggest that conversational profiling can support the differential diagnosis of functional and neurodegenerative memory disorders.

Differential expression of CCN-family members in primary human bone marrow-derived mesenchymal stem cells during osteogenic, chondrogenic and adipogenic differentiation

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Hendrich Christian

2005-03-01

decrease in CYR61/CCN1 expression during the differentiation pathways of mesenchymal stem cells into osteoblasts, adipocytes and chondrocytes suggests a specific role of CYR61/CCN1 for maintenance of the stem cell phenotype. The differential expression of CTGF/CCN2, WISP2/CCN5, WISP3/CCN6 and mainly CYR61/CCN1 indicates, that these members of the CCN-family might be important regulators for bone marrow-derived mesenchymal stem cells in the regulation of proliferation and initiation of specific differentiation pathways.

Reliability analysis and initial requirements for FC systems and stacks

Science.gov (United States)

Åström, K.; Fontell, E.; Virtanen, S.

In the year 2000 Wärtsilä Corporation started an R&D program to develop SOFC systems for CHP applications. The program aims to bring to the market highly efficient, clean and cost competitive fuel cell systems with rated power output in the range of 50-250 kW for distributed generation and marine applications. In the program Wärtsilä focuses on system integration and development. System reliability and availability are key issues determining the competitiveness of the SOFC technology. In Wärtsilä, methods have been implemented for analysing the system in respect to reliability and safety as well as for defining reliability requirements for system components. A fault tree representation is used as the basis for reliability prediction analysis. A dynamic simulation technique has been developed to allow for non-static properties in the fault tree logic modelling. Special emphasis has been placed on reliability analysis of the fuel cell stacks in the system. A method for assessing reliability and critical failure predictability requirements for fuel cell stacks in a system consisting of several stacks has been developed. The method is based on a qualitative model of the stack configuration where each stack can be in a functional, partially failed or critically failed state, each of the states having different failure rates and effects on the system behaviour. The main purpose of the method is to understand the effect of stack reliability, critical failure predictability and operating strategy on the system reliability and availability. An example configuration, consisting of 5 × 5 stacks (series of 5 sets of 5 parallel stacks) is analysed in respect to stack reliability requirements as a function of predictability of critical failures and Weibull shape factor of failure rate distributions.

Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

Science.gov (United States)

Nichols, Sharon L; Bethel, James; Kapogiannis, Bill G; Li, Tiandong; Woods, Steven P; Patton, E Doyle; Ren, Weijia; Thornton, Sarah E; Major-Wilson, Hanna O; Puga, Ana M; Sleasman, John W; Rudy, Bret J; Wilson, Craig M; Garvie, Patricia A

2016-04-01

Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

Optimization of differentiation time of mesenchymal-stem-cell to tenocyte under a cyclic stretching with a microgrooved culture membrane and selected measurement cells.

Science.gov (United States)

Morita, Yasuyuki; Yamashita, Takahiro; Toku, Toku; Ju, Yang

2018-01-01

There is a need for efficient stem cell-to-tenocyte differentiation techniques for tendon tissue engineering. More than 1 week is required for tenogenic differentiation with chemical stimuli, including co-culturing. Research has begun to examine the utility of mechanical stimuli, which reduces the differentiation time to several days. However, the precise length of time required to differentiate human bone marrow-derived mesenchymal stem cells (hBMSCs) into tenocytes has not been clarified. Understanding the precise time required is important for future tissue engineering projects. Therefore, in this study, a method was developed to more precisely determine the length of time required to differentiate hBMSCs into tenocytes with cyclic stretching stimulus. First, it had to be determined how stretching stimulation affected the cells. Microgrooved culture membranes were used to suppress cell orientation behavior. Then, only cells oriented parallel to the microgrooves were selected and evaluated for protein synthesis levels for differentiation. The results revealed that growing cells on the microgrooved membrane and selecting optimally-oriented cells for measurement improved the accuracy of the differentiation evaluation, and that hBMSCs differentiated into tenocytes in approximately 10 h. The differentiation time corresponded to the time required for cellular cytoskeleton reorganization and cellular morphology alterations. This suggests that cells, when subjected to mechanical stimulus, secrete mRNAs and proteins for both cytoskeleton reorganization and differentiation.

Generalized differential transform method to differential-difference equation

International Nuclear Information System (INIS)

Zou Li; Wang Zhen; Zong Zhi

2009-01-01

In this Letter, we generalize the differential transform method to solve differential-difference equation for the first time. Two simple but typical examples are applied to illustrate the validity and the great potential of the generalized differential transform method in solving differential-difference equation. A Pade technique is also introduced and combined with GDTM in aim of extending the convergence area of presented series solutions. Comparisons are made between the results of the proposed method and exact solutions. Then we apply the differential transform method to the discrete KdV equation and the discrete mKdV equation, and successfully obtain solitary wave solutions. The results reveal that the proposed method is very effective and simple. We should point out that generalized differential transform method is also easy to be applied to other nonlinear differential-difference equation.

Comparative Transcriptomics Reveals Jasmonic Acid-Associated Metabolism Related to Cotton Fiber Initiation.

Directory of Open Access Journals (Sweden)

Liman Wang

Full Text Available Analysis of mutants and gene expression patterns provides a powerful approach for investigating genes involved in key stages of plant fiber development. In this study, lintless-fuzzless XinWX and linted-fuzzless XinFLM with a single genetic locus difference for lint were used to identify differentially expressed genes. Scanning electron microscopy showed fiber initiation in XinFLM at 0 days post anthesis (DPA. Fiber transcriptional profiling of the lines at three initiation developmental stages (-1, 0, 1 DPA was performed using an oligonucleotide microarray. Loop comparisons of the differentially expressed genes within and between the lines was carried out, and functional classification and enrichment analysis showed that gene expression patterns during fiber initiation were heavily associated with hormone metabolism, transcription factor regulation, lipid transport, and asparagine biosynthetic processes, as previously reported. Further, four members of the allene-oxide cyclase (AOC family that function in jasmonate biosynthesis were parallel up-regulation in fiber initiation, especially at -1 DPA, compared to other tissues and organs in linted-fuzzed TM-1. Real time-quantitative PCR (RT-qPCR analysis in different fiber mutant lines revealed that AOCs were up-regulated higher at -1 DPA in lintless-fuzzless than that in linted-fuzzless and linted-fuzzed materials, and transcription of the AOCs was increased under jasmonic acid (JA treatment. Expression analysis of JA biosynthesis-associated genes between XinWX and XinFLM showed that they were up-regulated during fiber initiation in the fuzzless-lintless mutant. Taken together, jasmonic acid-associated metabolism was related to cotton fiber initiation. Parallel up-regulation of AOCs expression may be important for normal fiber initiation development, while overproduction of AOCs might disrupt normal fiber development.

Hepatocellular carcinoma with neuroendocrine differentiation: clinical and imaging findings in five patients

International Nuclear Information System (INIS)

Park, Seong Hoon; Kang, Myeong Jin; Cho, Jin Han

2008-01-01

To describe the clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation, which is an extremely rare variant of hepatocellular carcinoma. We collected five patients who had histopathologically proven hepatocellular carcinoma with neuroendocrine differentiation, and described morphologic feature, enhancement pattern of tumors, extrahepatic manifestation and clinical findings. At CT, the tumor size ranged from 8 to 17 cm (mean: 12 cm) in maximum diameter. The tumor margin was well-defined and smooth in four patients and all tumors were heterogeneously hypoattenuating. Four tumor showed rim enhancement on arterial and portal phases. Local invasion to the portal vein, intrahepatic duct and gallbladder were seen. Extrahepatic manifestations included hepatic metastases, lymph node metastasis. At ultrasonography, the tumor showed heterogeneously hyperechoic in all patients and hypoechoic rim was found in four patients. Of four patients who were followed up, one survived for 16 months after initial diagnosis, while the other three died within 3 months after initial diagnosis. As described above, clinical and imaging findings of hepatocellular carcinoma with neuroendocrine differentiation were not specific. However, this rare variant of hepatocellular carcinoma could be considered when hepatic tumor is found in an advanced stage and shows persistent rim enhancement at CT

Differential Expression of Tyrosine Hydroxylase Protein and Apoptosis-Related Genes in Differentiated and Undifferentiated SH-SY5Y Neuroblastoma Cells Treated with MPP+

Directory of Open Access Journals (Sweden)

Kawinthra Khwanraj

2015-01-01

Full Text Available The human neuroblastoma SH-SY5Y cell line has been used as a dopaminergic cell model for Parkinson’s disease research. Whether undifferentiated or differentiated SH-SY5Y cells are more suitable remains controversial. This study aims to evaluate the expression of apoptosis-related mRNAs activated by MPP+ and evaluate the differential expression of tyrosine hydroxylase (TH in undifferentiated and retinoic acid- (RA- induced differentiated cells. The western blot results showed a gradual decrease in TH in undifferentiated cells and a gradual increase in TH in differentiated cells from days 4 to 10 after cell plating. Immunostaining revealed a gradual increase in TH along with neuritic outgrowth in differentiated cells on days 4 and 7 of RA treatment. For the study on cell susceptibility to MPP+ and the expression of apoptosis-related genes, MTT assay showed a decrease in cell viability to approximately 50% requiring 500 and 1000 μM of MPP+ for undifferentiated and RA-differentiated cells, respectively. Using real-time RT-PCR, treatment with 500 μM MPP+ led to significant increases in the Bax/Bcl-2 ratio, p53, and caspase-3 in undifferentiated cells but was without significance in differentiated cells. In conclusion, differentiated cells may be more suitable, and the shorter duration of RA differentiation may make the SH-SY5Y cell model more accessible.

Test generator development for differential equations for lms moodle

Directory of Open Access Journals (Sweden)

Анна Александровна Муханова

2014-12-01

Full Text Available This article discusses the basic mechanisms of the test generator for differential equations, developed by the authors. The generator is designed to generate a large number of test questions in accordance with user-defined rules, which include: the number of tasks required for each type of differential equation, and the tasks difficulty, controlled by the nesting level of recursive functions. The generator produces a test file format GIFT, which is a plain text file.

Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

Energy Technology Data Exchange (ETDEWEB)

Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Dunham, Ian [EMBL-European Bioinformatics Institute (EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD (United Kingdom); Murai, Kasumi [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom); Jones, Philip H., E-mail: phj20@cam.ac.uk [MRC Cancer Cell Unit, Hutchison-MRC Research Centre, Addenbrooke' s Hospital, Cambridge CB2 0XZ (United Kingdom)

2011-07-01

Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

Hes6 is required for actin cytoskeletal organization in differentiating C2C12 myoblasts

International Nuclear Information System (INIS)

Malone, Caroline M.P.; Domaschenz, Renae; Amagase, Yoko; Dunham, Ian; Murai, Kasumi; Jones, Philip H.

2011-01-01

Hes6 is a member of the hairy-enhancer-of-split family of transcription factors that regulate proliferating cell fate in development and is known to be expressed in developing muscle. Here we investigate its function in myogenesis in vitro. We show that Hes6 is a direct transcriptional target of the myogenic transcription factors MyoD and Myf5, indicating that it is integral to the myogenic transcriptional program. The localization of Hes6 protein changes during differentiation, becoming predominantly nuclear. Knockdown of Hes6 mRNA levels by siRNA has no effect on cell cycle exit or induction of myosin heavy chain expression in differentiating C2C12 myoblasts, but F-actin filament formation is disrupted and both cell motility and myoblast fusion are reduced. The knockdown phenotype is rescued by expression of Hes6 cDNA resistant to siRNA. These results define a novel role for Hes6 in actin cytoskeletal dynamics in post mitotic myoblasts.

Committed to Differentiation and Engagement: A Case Study of Two American Secondary Social Studies Teachers

Directory of Open Access Journals (Sweden)

Derek Anderson

2014-05-01

Full Text Available This case study examines two 10th-grade US History teachers who collaborated to create and implement an integrated, thematic eight-week unit on war with an emphasis differentiated instruction. Drawing on the National Council for the Social Studies (2010 framework for powerful and purposeful social studies instruction, the case study uses multiple sources of data, including 38 lesson observations, analyses of the teachers’ lesson plans and student work, and interviews of teachers. Initially, the teachers were successful at engaging students in simulations, small-group discussions, and higher-order thinking. As the unit progressed, however, the teachers reverted to transmission-style teaching with an emphasis on breadth over depth. Changing teaching practice requires overcoming barriers associated with prior experiences and deeply-held beliefs about teaching and learning.

A model-based initial guess for estimating parameters in systems of ordinary differential equations.

Science.gov (United States)

Dattner, Itai

2015-12-01

The inverse problem of parameter estimation from noisy observations is a major challenge in statistical inference for dynamical systems. Parameter estimation is usually carried out by optimizing some criterion function over the parameter space. Unless the optimization process starts with a good initial guess, the estimation may take an unreasonable amount of time, and may converge to local solutions, if at all. In this article, we introduce a novel technique for generating good initial guesses that can be used by any estimation method. We focus on the fairly general and often applied class of systems linear in the parameters. The new methodology bypasses numerical integration and can handle partially observed systems. We illustrate the performance of the method using simulations and apply it to real data. © 2015, The International Biometric Society.

R[2, 4; 2: 6] rational one-step numerical integrator for initial value ...

African Journals Online (AJOL)

Abstract. A method of order six is proposed for solving singular initial value problems in ordinary differential equations. It compares favourably with existing schemes. Journal of the Nigerian Association of Mathematical Physics Vol. 9 2005: pp. 285-294 ...

Differential memory in the Earth's magnetotail

International Nuclear Information System (INIS)

Burkhart, G.R.; Chen, J.

1991-01-01

The process of differential memory is quantitatively studied in the modified Harris magnetotail geometry. This process arises as a consequence of nonlinear particle dynamics in the magnetotail which gives rise to partitioning of phase space into disjoint regions. Different regions are occupied by distinct classes of orbits and have widely separated time scales. This paper gives the first study of the time scales and potentially observable signatures in plasma distribution functions associated with the process of differential memory. It is foudn that the effective trapping time of stochastic orbits plays a critical role in differential memory and that in the magnetotail geometry, this time has resonances at certain values of the parameter H. A scaling law H 1/4 has been found for this previously unknown resonance effect. This scaling is directly related to the phase space structures of this stochastic system and leads to signatures in the distribution functions, and their velocity moments (density, velocity components, and kinetic temperatures) are computed following a prescribed change in the boundary conditions. The relationships between the initial changes and the time-asymptotic distribution functions are discussed. The results depend only on the large-scale phase space structures and not on individual chaotic orbits

MYC activation is a hallmark of cancer initiation and maintenance.

Science.gov (United States)

Gabay, Meital; Li, Yulin; Felsher, Dean W

2014-06-02

The MYC proto-oncogene has been implicated in the pathogenesis of most types of human tumors. MYC activation alone in many normal cells is restrained from causing tumorigenesis through multiple genetic and epigenetically controlled checkpoint mechanisms, including proliferative arrest, apoptosis, and cellular senescence. When pathologically activated in a permissive epigenetic and/or genetic context, MYC bypasses these mechanisms, enforcing many of the "hallmark" features of cancer, including relentless tumor growth associated with DNA replication and transcription, cellular proliferation and growth, protein synthesis, and altered cellular metabolism. MYC mandates tumor cell fate, by inducing stemness and blocking cellular senescence and differentiation. Additionally, MYC orchestrates changes in the tumor microenvironment, including the activation of angiogenesis and suppression of the host immune response. Provocatively, brief or even partial suppression of MYC back to its physiological levels of activation can result in the restoration of intrinsic checkpoint mechanisms, resulting in acute and sustained tumor regression, associated with tumor cells undergoing proliferative arrest, differentiation, senescence, and apoptosis, as well as remodeling of the tumor microenvironment, recruitment of an immune response, and shutdown of angiogenesis. Hence, tumors appear to be "addicted" to MYC because of both tumor cell-intrinsic, cell-autonomous and host-dependent, immune cell-dependent mechanisms. Both the trajectory and persistence of many human cancers require sustained MYC activation. Multiscale mathematical modeling may be useful to predict when tumors will be addicted to MYC. MYC is a hallmark molecular feature of both the initiation and maintenance of tumorigenesis. Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Molecular biological features of male germ cell differentiation

Science.gov (United States)

HIROSE, MIKA; TOKUHIRO, KEIZO; TAINAKA, HITOSHI; MIYAGAWA, YASUSHI; TSUJIMURA, AKIRA; OKUYAMA, AKIHIKO; NISHIMUNE, YOSHITAKE

2007-01-01

Somatic cell differentiation is required throughout the life of a multicellular organism to maintain homeostasis. In contrast, germ cells have only one specific function; to preserve the species by conveying the parental genes to the next generation. Recent studies of the development and molecular biology of the male germ cell have identified many genes, or isoforms, that are specifically expressed in the male germ cell. In the present review, we consider the unique features of male germ cell differentiation. (Reprod Med Biol 2007; 6: 1–9) PMID:29699260

Hybrid Differential Dynamic Programming with Stochastic Search

Science.gov (United States)

Aziz, Jonathan; Parker, Jeffrey; Englander, Jacob

2016-01-01

Differential dynamic programming (DDP) has been demonstrated as a viable approach to low-thrust trajectory optimization, namely with the recent success of NASAs Dawn mission. The Dawn trajectory was designed with the DDP-based Static Dynamic Optimal Control algorithm used in the Mystic software. Another recently developed method, Hybrid Differential Dynamic Programming (HDDP) is a variant of the standard DDP formulation that leverages both first-order and second-order state transition matrices in addition to nonlinear programming (NLP) techniques. Areas of improvement over standard DDP include constraint handling, convergence properties, continuous dynamics, and multi-phase capability. DDP is a gradient based method and will converge to a solution nearby an initial guess. In this study, monotonic basin hopping (MBH) is employed as a stochastic search method to overcome this limitation, by augmenting the HDDP algorithm for a wider search of the solution space.

Surface modification of hydroxyapatite with poly(methyl methacrylate) via surface-initiated ATRP

Energy Technology Data Exchange (ETDEWEB)

Wang Yan; Zhang Xi; Yan Jinliang; Xiao Yan [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 (China); Lang Meidong, E-mail: mdlang@ecust.edu.cn [Shanghai Key Laboratory of Advanced Polymeric Materials, Key Laboratory for Ultrafine Materials of Ministry of Education, School of Materials Science and Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237 (China)

2011-05-01

This article describes the fabrication of hydroxyapatite (HAP) nanocomposites grafted with poly(methyl methacrylate) (PMMA). Surface-initiated atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) was carried out from hydroxyapatite particles derivatized with ATRP initiators. The structure and properties of the nanocomposites were investigated by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), differential scanning calorimeter (DSC) measurements, and contact angle analyses. TGA was used to estimate the grafting density of ATRP initiators (0.49 initiator/nm{sup 2}) and the amount of grafted PMMA on the HAP surface. The contact angle analyses indicated that grafting PMMA onto the HAP surface dramatically increased the hydrophobicity of the surface. Moreover, the HAP nanocomposites showed excellent dispersibility in both aqueous solution and organic solvent.

Surface modification of hydroxyapatite with poly(methyl methacrylate) via surface-initiated ATRP

International Nuclear Information System (INIS)

Wang Yan; Zhang Xi; Yan Jinliang; Xiao Yan; Lang Meidong

2011-01-01

This article describes the fabrication of hydroxyapatite (HAP) nanocomposites grafted with poly(methyl methacrylate) (PMMA). Surface-initiated atom transfer radical polymerization (ATRP) of methyl methacrylate (MMA) was carried out from hydroxyapatite particles derivatized with ATRP initiators. The structure and properties of the nanocomposites were investigated by thermogravimetric analysis (TGA), transmission electron microscopy (TEM), differential scanning calorimeter (DSC) measurements, and contact angle analyses. TGA was used to estimate the grafting density of ATRP initiators (0.49 initiator/nm 2 ) and the amount of grafted PMMA on the HAP surface. The contact angle analyses indicated that grafting PMMA onto the HAP surface dramatically increased the hydrophobicity of the surface. Moreover, the HAP nanocomposites showed excellent dispersibility in both aqueous solution and organic solvent.

Poorly-differentiated colorectal neuroendocrine tumour: CT differentiation from well-differentiated neuroendocrine tumour and poorly-differentiated adenocarcinomas

Energy Technology Data Exchange (ETDEWEB)

Kang, Ji Hee [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Kim, Se Hyung [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Han, Joon Koo [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea, Republic of)

2017-09-15

The differentiation of poorly-differentiated neuroendocrine tumours (PD-NETs), well-differentiated NETs (WD-NETs), and adenocarcinomas (ADCs) is important due to different management options and prognoses. This study is to find the differential CT features of colorectal PD-NETs from WD-NETs and ADCs. CT features of 25 colorectal WD-NETs, 36 PD-NETs, and 36 ADCs were retrospectively reviewed. Significant variables were assessed using univariate and multivariate analyses. Receiver operating characteristics analysis determined the optimal cut-off value of tumour and lymph node (LN) size. Large size, rectum location, ulceroinfiltrative morphology without intact overlying mucosa, heterogeneous attenuation with necrosis, presence of ≥3 enlarged LNs, and metastasis were significant variables to differentiate PD-NETs from WD-NETs (P < 0.05). High attenuation on arterial phase, persistently high enhancement pattern, presence of ≥6 enlarged LNs, large LN size, and wash-in/wash-out enhancement pattern of liver metastasis were significant variables to differentiate PD-NETs from ADCs (P < 0.05). Compared to WD-NETs, colorectal PD-NETs are usually large, heterogeneous, and ulceroinfiltrative mass without intact overlying mucosa involving enlarged LNs and metastasis. High attenuation on arterial phase, presence of enlarged LNs with larger size and greater number, and wash-in/wash-out enhancement pattern of liver metastasis can be useful CT discriminators of PD-NETs from ADCs. (orig.)

RNF20 and USP44 regulate stem cell differentiation by modulating H2B monoubiquitylation

Science.gov (United States)

Fuchs, Gilad; Shema, Efrat; Vesterman, Rita; Kotler, Eran; Wolchinsky, Zohar; Wilder, Sylvia; Golomb, Lior; Pribluda, Ariel; Zhang, Feng; Haj-Yahya, Mahmood; Feldmesser, Ester; Brik, Ashraf; Yu, Xiaochun; Hanna, Jacob; Aberdam, Daniel; Domany, Eytan; Oren, Moshe

2012-01-01

Summary Embryonic stem cells (ESC) maintain high genomic plasticity, essential for their capacity to enter diverse differentiation pathways. Post-transcriptional modifications of chromatin histones play a pivotal role in maintaining this plasticity. We now report that one such modification, monoubiquitylation of histone H2B on lysine 120 (H2Bub1), catalyzed by the E3 ligase RNF20, increases during ESC differentiation and is required for efficient execution of this process. This increase is particularly important for the transcriptional induction of relatively long genes during ESC differentiation. Furthermore, we identify the deubiquitinase USP44 as a negative regulator of H2B ubiquitylation, whose downregulation during ESC differentiation contributes to the increase in H2Bub1. Our findings suggest that optimal ESC differentiation requires dynamic changes in H2B ubiquitylation patterns, which must occur in a timely and well-coordinated manner. PMID:22681888

Initial data sets for the Schwarzschild spacetime

International Nuclear Information System (INIS)

Gomez-Lobo, Alfonso Garcia-Parrado; Kroon, Juan A. Valiente

2007-01-01

A characterization of initial data sets for the Schwarzschild spacetime is provided. This characterization is obtained by performing a 3+1 decomposition of a certain invariant characterization of the Schwarzschild spacetime given in terms of concomitants of the Weyl tensor. This procedure renders a set of necessary conditions--which can be written in terms of the electric and magnetic parts of the Weyl tensor and their concomitants--for an initial data set to be a Schwarzschild initial data set. Our approach also provides a formula for a static Killing initial data set candidate--a KID candidate. Sufficient conditions for an initial data set to be a Schwarzschild initial data set are obtained by supplementing the necessary conditions with the requirement that the initial data set possesses a stationary Killing initial data set of the form given by our KID candidate. Thus, we obtain an algorithmic procedure of checking whether a given initial data set is Schwarzschildean or not

Solving the Telegraph and Oscillatory Differential Equations by a Block Hybrid Trigonometrically Fitted Algorithm

Directory of Open Access Journals (Sweden)

F. F. Ngwane

2015-01-01

Full Text Available We propose a block hybrid trigonometrically fitted (BHT method, whose coefficients are functions of the frequency and the step-size for directly solving general second-order initial value problems (IVPs, including systems arising from the semidiscretization of hyperbolic Partial Differential Equations (PDEs, such as the Telegraph equation. The BHT is formulated from eight discrete hybrid formulas which are provided by a continuous two-step hybrid trigonometrically fitted method with two off-grid points. The BHT is implemented in a block-by-block fashion; in this way, the method does not suffer from the disadvantages of requiring starting values and predictors which are inherent in predictor-corrector methods. The stability property of the BHT is discussed and the performance of the method is demonstrated on some numerical examples to show accuracy and efficiency advantages.

Clinical and histopathological differential diagnosis of eosinophilic pustular folliculitis.

Science.gov (United States)

Fujiyama, Toshiharu; Tokura, Yoshiki

2013-06-01

Eosinophilic pustular folliculitis (EPF) is an inflammatory disease characterized by repeated pruritic follicular papules and pustules arranged in arcuate plaques, and folliculotropic infiltration of eosinophils. The diagnosis of EPF is occasionally difficult and problematic because EPF may share the clinical appearance and histological findings with other diseases. Moreover, EPF has several clinical subtypes, including the classical type, infantile type and immunosuppression-associated type. Because the therapies of EPF are relatively specific as compared to eczematous disorders, accurate diagnosis is essential for the management of EPF. Clinical differential diagnoses include tinea, acne, rosacea, eczematous dermatitis, granuloma faciale, autoimmune annular erythema, infestations and pustular dermatosis. Histologically, cutaneous diseases with eosinophilic infiltrates can be differentially diagnosed. Follicular mucinosis, mycosis fungoides and other cutaneous T-cell lymphomas are the most important differential diagnoses both clinically and histopathologically. It should be kept in mind particularly that the initial lesions of cutaneous T-cell lymphoma resemble EPF. © 2013 Japanese Dermatological Association.

Financial planning for major initiatives: a framework for success.

Science.gov (United States)

Harris, John M

2007-11-01

A solid framework for assessing a major strategic initiative consists of four broad steps: Initial considerations, including level of analysis required and resources that will be brought to bear. Preliminary financial estimates for board approval to further assess the initiative. Assessment of potential partners' interest in the project. Feasibility analysis for board green light.

A semi-analytical approach for solving of nonlinear systems of functional differential equations with delay

Science.gov (United States)

Rebenda, Josef; Šmarda, Zdeněk

2017-07-01

In the paper, we propose a correct and efficient semi-analytical approach to solve initial value problem for systems of functional differential equations with delay. The idea is to combine the method of steps and differential transformation method (DTM). In the latter, formulas for proportional arguments and nonlinear terms are used. An example of using this technique for a system with constant and proportional delays is presented.

Numerical Methods for Partial Differential Equations

CERN Document Server

Guo, Ben-yu

1987-01-01

These Proceedings of the first Chinese Conference on Numerical Methods for Partial Differential Equations covers topics such as difference methods, finite element methods, spectral methods, splitting methods, parallel algorithm etc., their theoretical foundation and applications to engineering. Numerical methods both for boundary value problems of elliptic equations and for initial-boundary value problems of evolution equations, such as hyperbolic systems and parabolic equations, are involved. The 16 papers of this volume present recent or new unpublished results and provide a good overview of current research being done in this field in China.

Pricing strategies under heterogeneous service requirements

NARCIS (Netherlands)

Mandjes, M.R.H.

This paper analyzes a communication network, used by customers with heterogeneous service requirements. We investigate priority queueing as a way to establish service differentiation. It is assumed that there is an infinite population of customers, who join the network as long as their utility

Galectin-12 in Cellular Differentiation, Apoptosis and Polarization

Directory of Open Access Journals (Sweden)

Lei Wan

2018-01-01

Full Text Available Galectin-12 is a member of a family of mammalian lectins characterized by their affinity for β-galactosides and consensus amino acid sequences. The protein structure consists of a single polypeptide chain containing two carbohydrate-recognition domains joined by a linker region. Galectin-12 is predominantly expressed in adipose tissue, but is also detected in macrophages and other leukocytes. Downregulation of galectin-12 in mouse 3T3-L1 cells impairs their differentiation into adipocytes. Conversely, overexpression of galectin-12 in vitro induces cell cycle arrest in G1 and apoptosis. Upregulation of galectin-12 and initiation of G1 cell cycle arrest are associated with driving pre-adipocytes toward terminal differentiation. Galectin-12 deficiency increases insulin sensitivity and glucose tolerance in obese animals. Galectin-12 inhibits macrophage polarization to the M2 population, enhancing inflammation and decreasing insulin sensitivity in adipocytes. Galectin-12 also affects myeloid differentiation, which is associated with chemotherapy resistance. In addition to highlighting the above-mentioned aspects, this review also discusses the potential clinical applications of modulating the function of galectin-12.

Development and validation of the measure of initial attraction- Short Interest Scale (MIA-I

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David Rodrigues

2015-06-01

Full Text Available Unilateral initial attraction (UIA is a positive affective reaction following a unilateral perception of an unknown target, defining the first stage in developing a new interpersonal relationship. Although little attention is given to this construct, literature suggests it has a physiological activation component as well as an interpersonal interest component. However, this interest component emerges as necessary to willingly approach another person and eventually initiate interaction. Based on these evidences, we developed and validated the Measure of Initial Attraction - Interest Short Scale (MIA-I in a sample of Portuguese-speaking individuals (Study 1, N = 544. Results suggest the MIA-I is a valid and reliable instrument (Study 1; Study 2a, and show its capacity to discriminate UIA across different relationships (Study 1 and to differentiate UIA from passion and love (Study 1. Towards an unknown target, the MIA-I also distinguished UIA from liking (Study 2b. These results show that the MIA-I assesses a specific construct, differentiated from liking, passion and love, and suggest its importance to understand the UIA phenomenon.

Integro-differential equation approach extended to larger nuclei

International Nuclear Information System (INIS)

Adam, R.M.; Sofianos, S.A.; Fiedeldey, H.; Fabre de la Ripelle, M.

1992-01-01

We extend the integro-differential equation approach (IDEA) from few-nucleon to closed-shell and closed-subshell nuclei and outline the analytical methods required for the calculation of the density functions, which enter into the integro-differential equations. These contain all the physics for a system of fermions associated with the Pauli principle. In order to test the accuracy of the IDEA comparisons are made of the binding energies of 4 He, 12 C and 16 O obtained with effective potentials using the hypercentral approximation (HCA) providing a variational solution without correlations, the IDEA which fully includes the two-body correlations, the S-states integro-differential equation (SIDE) valid for potentials operating only on pairs in the S-state and those calculated by several variational or perturbative methods in the literature. (author)

Low swing differential logic for mixed signal applications

International Nuclear Information System (INIS)

Fischer, P.; Kraft, E.

2004-01-01

Low swing differential logic operated at a constant bias current is a promising approach to reduce the switching noise in sensitive mixed mode circuits. Most differential logic families do not allow a significant change in bias current between cells so that it is difficult to optimize the power consumption for a required speed. A nonlinear load circuit for differential current-steering logic consisting of a current source in parallel with a diode connected FET is therefore proposed. The logic levels can be easily adjusted with an external supply voltage so that the circuit design is significantly simplified. As an example application a counter for the use in pixel readout chips is presented. The layout area using radiation hard design rules is not significantly larger than CMOS. The logic can be operated at very low power

Derivation of a macroscale formulation for a class of nonlinear partial differential equations

International Nuclear Information System (INIS)

Pantelis, G.

1995-05-01

A macroscale formulation is constructed from a system of partial differential equations which govern the microscale dependent variables. The construction is based upon the requirement that the solutions of the macroscale partial differential equations satisfy, in some approximate sense, the system of partial differential equations associated with the microscale. These results are restricted to the class of nonlinear partial differential equations which can be expressed as polynomials of the dependent variables and their partial derivatives up to second order. A linear approximation of transformations of second order contact manifolds is employed. 6 refs

Collage-based approaches for elliptic partial differential equations inverse problems

Science.gov (United States)

Yodzis, Michael; Kunze, Herb

2017-01-01

The collage method for inverse problems has become well-established in the literature in recent years. Initial work developed a collage theorem, based upon Banach's fixed point theorem, for treating inverse problems for ordinary differential equations (ODEs). Amongst the subsequent work was a generalized collage theorem, based upon the Lax-Milgram representation theorem, useful for treating inverse problems for elliptic partial differential equations (PDEs). Each of these two different approaches can be applied to elliptic PDEs in one space dimension. In this paper, we explore and compare how the two different approaches perform for the estimation of the diffusivity for a steady-state heat equation.

Introduction to partial differential equations

CERN Document Server

Borthwick, David

2016-01-01

This modern take on partial differential equations does not require knowledge beyond vector calculus and linear algebra. The author focuses on the most important classical partial differential equations, including conservation equations and their characteristics, the wave equation, the heat equation, function spaces, and Fourier series, drawing on tools from analysis only as they arise.Within each section the author creates a narrative that answers the five questions: (1) What is the scientific problem we are trying to understand? (2) How do we model that with PDE? (3) What techniques can we use to analyze the PDE? (4) How do those techniques apply to this equation? (5) What information or insight did we obtain by developing and analyzing the PDE? The text stresses the interplay between modeling and mathematical analysis, providing a thorough source of problems and an inspiration for the development of methods.

Numerical models for differential problems

CERN Document Server

Quarteroni, Alfio

2017-01-01

In this text, we introduce the basic concepts for the numerical modelling of partial differential equations. We consider the classical elliptic, parabolic and hyperbolic linear equations, but also the diffusion, transport, and Navier-Stokes equations, as well as equations representing conservation laws, saddle-point problems and optimal control problems. Furthermore, we provide numerous physical examples which underline such equations. We then analyze numerical solution methods based on finite elements, finite differences, finite volumes, spectral methods and domain decomposition methods, and reduced basis methods. In particular, we discuss the algorithmic and computer implementation aspects and provide a number of easy-to-use programs. The text does not require any previous advanced mathematical knowledge of partial differential equations: the absolutely essential concepts are reported in a preliminary chapter. It is therefore suitable for students of bachelor and master courses in scientific disciplines, an...

Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

Energy Technology Data Exchange (ETDEWEB)

Lasrich, Dorothee; Bartelt, Alexander [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany); Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au [Faculty of Pharmacy A15, The University of Sydney, Sydney, NSW 2006 (Australia); Heeren, Joerg, E-mail: heeren@uke.de [Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg (Germany)

2015-09-10

Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tert adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not differentiation. �

Competitive differentiation through brand extensions in the era of hyper competition

Directory of Open Access Journals (Sweden)

Claudiu-Catalin Munteanu

2015-03-01

Full Text Available In the era of hyper competition, competitive differentiation has become increasingly important. Brand extensions are used by companies across various industries for competitive differentiation. But in the era of hyper competition, a successful differentiation strategy requires that a brand emphasizes on uniqueness rather than commoditization. In this article, we make a case for creating a meaningful differentiation strategy. We emphasize the role of brand extensions for competitive differentiation and highlight the main perils of using brand extensions as a primary differentiation strategy. By using qualitative research, we identify primary objectives for brand extensions in practice. This investigation uses in-depth interviews with 14 senior brand managers across various industries to highlight brand portfolio strategies in relation to the brand differentiation strategy. Findings reveal that for business at the base of the pyramid, in markets such as Romania, brand managers are using brand extensions to increase sales or to boost short-term revenue rather than to implement a coherent differentiation strategy. We conclude with multiple recommendations for improving brand extension usage as a strategic instrument for creating meaningful differentiation in the era of hyper competition.

Integrity of the LXXLL motif in Stat6 is required for the inhibition of breast cancer cell growth and enhancement of differentiation in the context of progesterone

International Nuclear Information System (INIS)

Wei, Min; Zhu, Zhenggang; Zhang, Guofeng; He, Qi; Yang, Zhongyin; Wang, Zhiwei; Zhang, Qing; Liu, Bingya; Gu, Qinlong; Su, Liping; Yu, Yingyan

2014-01-01

Progesterone is essential for the proliferation and differentiation of mammary gland epithelium. Studies of breast cancer cells have demonstrated a biphasic progesterone response consisting of an initial proliferative burst followed by sustained growth arrest. However, the transcriptional factors acting with the progesterone receptor (PR) to mediate the effects of progesterone on mammary cell growth and differentiation remain to be determined. Recently, it was demonstrated that signal transducer and activator of transcription 6 (Stat6) is a cell growth suppressor. Similar to progesterone-bound PR, Stat6 acts by inducing the expression of the G1 cyclin-dependent kinase inhibitors p21 and p27. The possible interaction between Stat6 and progesterone pathways in mammary cells was therefore investigated in the present study. ChIP and luciferase were assayed to determine whether Stat6 induces p21 and p27 expression by recruitment at the proximal Sp1-binding sites of the gene promoters. Immunoprecipitation and Western blotting were performed to investigate the interaction between Stat6 and PR-B. The cellular DNA content and cell cycle distribution in breast cancer cells were analyzed by FACS. We found that Stat6 interacts with progesterone-activated PR in T47D cells. Stat6 synergizes with progesterone-bound PR to transactivate the p21 and p27 gene promoters at the proximal Sp1-binding sites. Moreover, Stat6 overexpression and knockdown, respectively, increased or prevented the induction of p21 and p27 gene expression by progesterone. Stat6 knockdown also abolished the inhibitory effects of progesterone on pRB phosphorylation, G1/S cell cycle progression, and cell proliferation. In addition, knockdown of Stat6 expression prevented the induction of breast cell differentiation markers, previously identified as progesterone target genes. Finally, Stat6 gene expression levels increased following progesterone treatment, indicating a positive auto-regulatory loop between PR and

The Differential Influence of Authoritative Parenting on the Initial Adjustment of Male and Female Traditional College Freshmen.

Science.gov (United States)

Hickman, Gregory P.; Toews, Michelle L.; Andrews, David W.

2001-01-01

Surveyed college freshmen to examine the relationship between gender, authoritative parenting, aptitude, self-esteem, initial academic achievement, and overall adjustment. Found that authoritative parenting style was positively related to males' initial grade point average, but not significantly associated with females'. (EV)

A gradual update method for simulating the steady-state solution of stiff differential equations in metabolic circuits.

Science.gov (United States)

Shiraishi, Emi; Maeda, Kazuhiro; Kurata, Hiroyuki

2009-02-01

Numerical simulation of differential equation systems plays a major role in the understanding of how metabolic network models generate particular cellular functions. On the other hand, the classical and technical problems for stiff differential equations still remain to be solved, while many elegant algorithms have been presented. To relax the stiffness problem, we propose new practical methods: the gradual update of differential-algebraic equations based on gradual application of the steady-state approximation to stiff differential equations, and the gradual update of the initial values in differential-algebraic equations. These empirical methods show a high efficiency for simulating the steady-state solutions for the stiff differential equations that existing solvers alone cannot solve. They are effective in extending the applicability of dynamic simulation to biochemical network models.

Introducing Differential Equations Students to the Fredholm Alternative--In Staggered Doses

Science.gov (United States)

Savoye, Philippe

2011-01-01

The development, in an introductory differential equations course, of boundary value problems in parallel with initial value problems and the Fredholm Alternative. Examples are provided of pairs of homogeneous and nonhomogeneous boundary value problems for which existence and uniqueness issues are considered jointly. How this heightens students'…

Orbit Determination from Tracking Data of Artificial Satellite Using the Method of Differential Correction

OpenAIRE

Byoung-Sun Lee; Jung-Hyun Jo; Sang-Young Park; Kyu-Hong Choi; Chun-Hwey Kim

1988-01-01

The differential correction process determining osculating orbital elements as correct as possible at a given instant of time from tracking data of artificial satellite was accomplished. Preliminary orbital elements were used as an initial value of the differential correction procedure and iterated until the residual of real observation(O) and computed observation(C) was minimized. Tracking satellite was NOAA-9 or TIROS-N series. Two types of tracking data were prediction data precomputed fro...

Existence and Uniqueness of Solutions for Coupled Systems of Higher-Order Nonlinear Fractional Differential Equations

Directory of Open Access Journals (Sweden)

Ahmad Bashir

2010-01-01

Full Text Available We study an initial value problem for a coupled Caputo type nonlinear fractional differential system of higher order. As a first problem, the nonhomogeneous terms in the coupled fractional differential system depend on the fractional derivatives of lower orders only. Then the nonhomogeneous terms in the fractional differential system are allowed to depend on the unknown functions together with the fractional derivative of lower orders. Our method of analysis is based on the reduction of the given system to an equivalent system of integral equations. Applying the nonlinear alternative of Leray-Schauder, we prove the existence of solutions of the fractional differential system. The uniqueness of solutions of the fractional differential system is established by using the Banach contraction principle. An illustrative example is also presented.

International EUREKA: Initialization Segment

International Nuclear Information System (INIS)

1982-02-01

The Initialization Segment creates the starting description of the uranium market. The starting description includes the international boundaries of trade, the geologic provinces, resources, reserves, production, uranium demand forecasts, and existing market transactions. The Initialization Segment is designed to accept information of various degrees of detail, depending on what is known about each region. It must transform this information into a specific data structure required by the Market Segment of the model, filling in gaps in the information through a predetermined sequence of defaults and built in assumptions. A principal function of the Initialization Segment is to create diagnostic messages indicating any inconsistencies in data and explaining which assumptions were used to organize the data base. This permits the user to manipulate the data base until such time the user is satisfied that all the assumptions used are reasonable and that any inconsistencies are resolved in a satisfactory manner

[Treatment and follow up protocol in differentiated thyroid carcinomas of follicular origin].

Science.gov (United States)

Rodrigues, Fernando; Limbert, Edward; Marques, Ana Paula; Santos, Ana Paula; Lopes, Carlos; Rodrigues, Elizabete; Borges, Fátima; Carrilho, Francisco; Castro, João Jácome de; Neto, João; Salgado, Lucília; Oliveira, Maria João

2005-01-01

Differentiated thyroid carcinoma of follicular origin (DTCFO), although not very frequent, has registered a raising incidence in the last decades. In the majority of the cases, DTCFO is a curable disease when treated and monitored by experienced, multidisciplinary teams. These factors contribute to an increasing number of DTCFO survivors requiring life-long monitoring, due to the possibility of occurrence of recurrences many years after the initial treatment. Several aspects of the treatment and management of these patients are still controversial. The present protocol represents the consensus of the members of the Grupo de Estudo da Tiróide of the Sociedade Portuguesa de Endocrinologia, Diabetes e Metabolismo. It aims to define guidelines, in agreement with the current state of the art and contemplating the necessary adaptations to local constrains, that ensure decreased mortality and protection of patients' quality of life, avoiding unnecessarily aggressive or ineffective treatments, optimizing the use of the available resources.

Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms.

Science.gov (United States)

Ma, Xing; Zhu, Xiujuan; Han, Yingying; Story, Benjamin; Do, Trieu; Song, Xiaoqing; Wang, Su; Zhang, Ying; Blanchette, Marco; Gogol, Madelaine; Hall, Kate; Peak, Allison; Anoja, Perera; Xie, Ting

2017-04-24

Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells of the Drosophila ovary through Piwi-associated RNA-mediated repression of transposon activities. Although it is highly expressed in germline stem cells (GSCs) and early progeny, it remains unclear whether it plays any roles in early GSC lineage development. Here we report that Aub promotes GSC self-renewal and GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs encoding self-renewal and differentiation factors in cultured GSCs. Aub controls GSC self-renewal by preventing DNA-damage-induced Chk2 activation and by translationally controlling the expression of self-renewal factors. It promotes GSC progeny differentiation by translationally controlling the expression of differentiation factors, including Bam. Therefore, this study reveals a function of Aub in GSCs and their progeny, which promotes translation of self-renewal and differentiation factors by directly binding to its target mRNAs and interacting with translational initiation factors. Copyright © 2017 Elsevier Inc. All rights reserved.

Cell-State Transitions Regulated by SLUG Are Critical for Tissue Regeneration and Tumor Initiation

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Sarah Phillips

2014-05-01

Full Text Available Perturbations in stem cell activity and differentiation can lead to developmental defects and cancer. We use an approach involving a quantitative model of cell-state transitions in vitro to gain insights into how SLUG/SNAI2, a key developmental transcription factor, modulates mammary epithelial stem cell activity and differentiation in vivo. In the absence of SLUG, stem cells fail to transition into basal progenitor cells, while existing basal progenitor cells undergo luminal differentiation; together, these changes result in abnormal mammary architecture and defects in tissue function. Furthermore, we show that in the absence of SLUG, mammary stem cell activity necessary for tissue regeneration and cancer initiation is lost. Mechanistically, SLUG regulates differentiation and cellular plasticity by recruiting the chromatin modifier lysine-specific demethylase 1 (LSD1 to promoters of lineage-specific genes to repress transcription. Together, these results demonstrate that SLUG plays a dual role in repressing luminal epithelial differentiation while unlocking stem cell transitions necessary for tumorigenesis.

Perturbation-expression analysis identifies RUNX1 as a regulator of human mammary stem cell differentiation.

Directory of Open Access Journals (Sweden)

Ethan S Sokol

2015-04-01

Full Text Available The search for genes that regulate stem cell self-renewal and differentiation has been hindered by a paucity of markers that uniquely label stem cells and early progenitors. To circumvent this difficulty we have developed a method that identifies cell-state regulators without requiring any markers of differentiation, termed Perturbation-Expression Analysis of Cell States (PEACS. We have applied this marker-free approach to screen for transcription factors that regulate mammary stem cell differentiation in a 3D model of tissue morphogenesis and identified RUNX1 as a stem cell regulator. Inhibition of RUNX1 expanded bipotent stem cells and blocked their differentiation into ductal and lobular tissue rudiments. Reactivation of RUNX1 allowed exit from the bipotent state and subsequent differentiation and mammary morphogenesis. Collectively, our findings show that RUNX1 is required for mammary stem cells to exit a bipotent state, and provide a new method for discovering cell-state regulators when markers are not available.

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

International Nuclear Information System (INIS)

Kohl, Yvonne; Gorjup, Erwin; Katsen-Globa, Alisa; Büchel, Claudia; Briesen, Hagen von; Thielecke, Hagen

2011-01-01

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4–21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

Effect of gold nanoparticles on adipogenic differentiation of human mesenchymal stem cells

Science.gov (United States)

Kohl, Yvonne; Gorjup, Erwin; Katsen-Globa, Alisa; Büchel, Claudia; von Briesen, Hagen; Thielecke, Hagen

2011-12-01

Gold nanoparticles are very attractive for biomedical products. However, there is a serious lack of information concerning the biological activity of nanosized gold in human tissue cells. An influence of nanoparticles on stem cells might lead to unforeseen consequences to organ and tissue functions as long as all cells arising from the initial stem cell might be subsequently damaged. Therefore the effect of negatively charged gold nanoparticles (9 and 95 nm), which are certified as reference material for preclinical biomedical research, on the adipogenic differentiation of human mesenchymal stem cells (hMSCs) is investigated here. Bone marrow hMSCs are chosen as differentiation model since bone marrow hMSCs are well characterized and their differentiation into the adipogenic lineage shows clear and easily detectable differentiation. In this study effects of gold nanoparticles on adipogenic differentiation are analyzed regarding fat storage and mitochondrial activity after different exposure times (4-21 days). Using time lapse microscopy the differentiation progress under chronically gold nanoparticle treatment is continuously investigated. In this preliminary study, chronically treatment of adipogenic differentiating hMSCs with gold nanoparticles resulted in a reduced number and size of lipid vacuoles and reduced mitochondrial activity depending on the applied concentration and the surface charge of the particles.

Differentiation of chondrocytes and scleroblasts during dorsal fin skeletogenesis in flounder larvae.

Science.gov (United States)

Suzuki, Tohru; Haga, Yutaka; Takeuchi, Toshio; Uji, Susumu; Hashimoto, Hisashi; Kurokawa, Tadahide

2003-01-01

In teleosts, the embryonic fin fold consists of a peridermis, an underlying epidermis and a small number of mesenchymal cells. Beginning from such a simple structure, the fin skeletons, including the proximal and distal radials and lepidotrichia (finrays), develop in the dorsal fin fold at the larval stage. Their process of skeletogenesis and embryonic origin are unclear. Using flounder larvae, we report the differentiation process for chondrocytes and scleroblasts prior to fin skeletogenesis and the effects of retinoic acid (RA) on it. In early larvae, the mesenchymal cells grow between the epidermis and spinal cord to form a line of periodical condensations, which are proximal radial primordia, to produce chondrocytes. The prescleroblasts, which ossify the proximal radial cartilages, differentiate in the mesenchymal cells remaining between the cartilages. Then, mesenchymal condensations occur between the distal ends of the proximal radials, forming distal radial primordia, to produce chondrocytes. Simultaneously, condensations occur between the distal radial primordia and peridermis, which are lepidotrichia primordia, to produce prescleroblasts. Exogenous RA specifically inhibits the mesenchymal condensation prior to the proximal radial formation together with the down-regulation of sonic hedgehog (shh) and patched (pta) expression, resulting in the loss of proximal radials. Thus, it was indicated that differentiation of the precursor cells of radials and lepidotrichia begins in the proximal part of the fin fold and that the initial mesenchymal condensation prior to the proximal radial formation is highly susceptible to the effects of RA. Lepidotrichia formation does not occur where proximal radials are absent, indicating that lepidotrichia differentiation requires interaction with the radial cartilages. To examine the suggestion that neural crest cells contribute to the medial fin skeletons, we localized the HNK-1 positive cells in flounder embryos and slug and

Retinoic acid functions as a key GABAergic differentiation signal in the basal ganglia.

Directory of Open Access Journals (Sweden)

Christina Chatzi

2011-04-01

Full Text Available Although retinoic acid (RA has been implicated as an extrinsic signal regulating forebrain neurogenesis, the processes regulated by RA signaling remain unclear. Here, analysis of retinaldehyde dehydrogenase mutant mouse embryos lacking RA synthesis demonstrates that RA generated by Raldh3 in the subventricular zone of the basal ganglia is required for GABAergic differentiation, whereas RA generated by Raldh2 in the meninges is unnecessary for development of the adjacent cortex. Neurospheres generated from the lateral ganglionic eminence (LGE, where Raldh3 is highly expressed, produce endogenous RA, which is required for differentiation to GABAergic neurons. In Raldh3⁻/⁻ embryos, LGE progenitors fail to differentiate into either GABAergic striatal projection neurons or GABAergic interneurons migrating to the olfactory bulb and cortex. We describe conditions for RA treatment of human embryonic stem cells that result in efficient differentiation to a heterogeneous population of GABAergic interneurons without the appearance of GABAergic striatal projection neurons, thus providing an in vitro method for generation of GABAergic interneurons for further study. Our observation that endogenous RA is required for generation of LGE-derived GABAergic neurons in the basal ganglia establishes a key role for RA signaling in development of the forebrain.

Genetic manipulation of RPS5 gene expression modulates the initiation of commitment of MEL cells to erythroid maturation: Implications in understanding ribosomopathies.

Science.gov (United States)

Vizirianakis, Ioannis S; Papachristou, Eleni T; Andreadis, Panagiotis; Zopounidou, Elena; Matragkou, Christina N; Tsiftsoglou, Asterios S

2015-07-01

Impairment of ribosome biogenesis contributes to the molecular pathophysiology of ribosomopathies by deregulating cell-lineage specific proliferation, differentiation and apoptosis decisions of haematopoietic progenitor cells. Here, using pro-erythroblast-like murine erythroleukemia (MEL) cells, a model system of erythroid maturation, we aimed to investigate whether genetic manipulation of RPS5 expression affects the capacity of cells to grow and differentiate in culture. Parental MEL cells stably transfected with full length RPS5 cDNA in sense (MEL-C14 culture) or antisense (MEL-antisenseRPS5 culture) orientation, as well as MEL cells transiently transfected with siRNAs specific for RPS5 gene silencing (MEL-RPS5siRNA culture) were assessed for their ability to fully execute their erythroid maturation program in culture. The data obtained thus far indicate that: a) MEL-antisenseRPS5 exhibit a pronounced delay in the initiation of differentiation, as well as an impairment of commitment, since the continuous presence of the inducer in culture is required for the cells to fully execute their erythroid maturation program. b) RNAi-mediating silencing of RPS5 gene expression resulted in the inability of MEL cells to differentiate; however, when these cells were allowed to recapitulate normal RPS5 gene expression levels they regained their differentiation capacity by accumulating high proportion of erythroid mature cells. c) Interestingly the latter, is accompanied by morphological changes of cells and an impairment of their proliferation and apoptosis potential. Such data for the first time correlate the RPS5 gene expression levels with the differentiation capacity of MEL cells in vitro, a fact that might also have implications in understanding ribosomopathies.

Oscillatory solutions of the Cauchy problem for linear differential equations

Directory of Open Access Journals (Sweden)

Gro Hovhannisyan

2015-06-01

Full Text Available We consider the Cauchy problem for second and third order linear differential equations with constant complex coefficients. We describe necessary and sufficient conditions on the data for the existence of oscillatory solutions. It is known that in the case of real coefficients the oscillatory behavior of solutions does not depend on initial values, but we show that this is no longer true in the complex case: hence in practice it is possible to control oscillatory behavior by varying the initial conditions. Our Proofs are based on asymptotic analysis of the zeros of solutions, represented as linear combinations of exponential functions.

Human Long Noncoding RNA Regulation of Stem Cell Potency and Differentiation

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Seahyoung Lee

2017-01-01

Full Text Available Because of their capability of differentiation into lineage-specific cells, stem cells are an attractive therapeutic modality in regenerative medicine. To develop an effective stem cell-based therapeutic strategy with predictable results, deeper understanding of the underlying molecular mechanisms of stem cell differentiation and/or pluripotency maintenance is required. Thus, reviewing the key factors involved in the transcriptional and epigenetic regulation of stem cell differentiation and maintenance is important. Accumulating data indicate that long noncoding RNAs (lncRNAs mediate numerous biological processes, including stem cell differentiation and maintenance. Here, we review recent findings on the human lncRNA regulation of stem cell potency and differentiation. Although the clinical implication of these lncRNAs is only beginning to be elucidated, it is anticipated that lncRNAs will become important therapeutic targets in the near future.

Chemical point detection using differential fluorescence from molecularly imprinted polymers

Science.gov (United States)

Pestov, Dmitry; Anderson, John E.; Nelson, Jean; Tepper, Gary C.

2004-12-01

Fluorescence represents one of the most attractive approaches for chemical sensing due to the abundant light produced by most fluorophores, resulting in excellent detection sensitivity. However, the broad and overlapping emission spectra of target and background species have made it difficult to perform species identification in a field instrument because of the need to perform spectral decomposition and analysis. This paper describes a new chemical sensing strategy based on differential fluorescence measurements from molecularly imprinted polymers, which eliminates the need to perform any spectral analysis. Species identification is accomplished by measuring the differential light output from a pair of polymers-one imprinted to a target species and the other identical, but not imprinted. The imprinted polymer selectively concentrates the target molecule and controls the energy (wavelength) of the emitted fluorescence signal and the differential output eliminates common mode signals associated with non-specific background interference. Because no spectral analysis is required, the sensors can be made extremely small and require very little power. Preliminary performance parameters from a prototype sensor are presented and discussed.

Primary root protophloem differentiation requires balanced phosphatidylinositol-4,5-biphosphate levels and systemically affects root branching.

NARCIS (Netherlands)

Rodriguez-Villalon, A.; Gujas, B.; van Wijk, R.; Munnik, T.; Hardtke, C.S.

2015-01-01

Protophloem is a specialized vascular tissue in growing plant organs, such as root meristems. In Arabidopsis mutants with impaired primary root protophloem differentiation, brevis radix (brx) and octopus (ops), meristematic activity and consequently overall root growth are strongly reduced. Second

Arithmetic differential equations on $GL_n$, I: differential cocycles

OpenAIRE

Buium, Alexandru; Dupuy, Taylor

2013-01-01

The theory of differential equations has an arithmetic analogue in which derivatives are replaced by Fermat quotients. One can then ask what is the arithmetic analogue of a linear differential equation. The study of usual linear differential equations is the same as the study of the differential cocycle from $GL_n$ into its Lie algebra given by the logarithmic derivative. However we prove here that there are no such cocycles in the context of arithmetic differential equations. In sequels of t...

Nuclear propulsion for the space exploration initiative

International Nuclear Information System (INIS)

Stanley, M.L.

1991-01-01

President Bush's speech of July 20, 1989, outlining a goal to go back to the moon and then Mars initiated the Space Exploration Initiative (SEI). The US Department of Defense (DOD), US Department of Energy (DOE), and NASA have been working together in the planning necessary to initiate a program to develop a nuclear propulsion system. Applications of nuclear technology for in-space transfer of personnel and cargo between Earth orbit and lunar or Martian orbit are being considered as alternatives to chemical propulsion systems. Mission and system concept studies conducted over the past 30 yr have consistently indicated that use of nuclear technology can substantially reduce in-space propellant requirements. A variety of nuclear technology options are currently being studied, including nuclear thermal rockets, nuclear electrical propulsion systems, and hybrid nuclear thermal rockets/nuclear electric propulsion concepts. Concept performance in terms of thrust, weight, power, and efficiency are dependent, and appropriate concept application is mission dependent (i.e., lunar, Mars, cargo, personnel, trajectory, transit time, payload). A comprehensive evaluation of mission application, technology performance capability and maturity, technology development programmatics, and safety characteristics is required to optimize both technology and mission selection to support the Presidential initiative

Differentiation potential of human adipose stem cells bioprinted with hyaluronic acid/gelatin-based bioink through microextrusion and visible light-initiated crosslinking.

Science.gov (United States)

Sakai, Shinji; Ohi, Hiromi; Hotta, Tomoki; Kamei, Hidenori; Taya, Masahito

2018-02-01

Bioprinting has a great potential to fabricate three-dimensional (3D) functional tissues and organs. In particular, the technique enables fabrication of 3D constructs containing stem cells while maintaining cell proliferation and differentiation abilities, which is believed to be promising in the fields of tissue engineering and regenerative medicine. We aimed to demonstrate the utility of the bioprinting technique to create hydrogel constructs consisting of hyaluronic acid (HA) and gelatin derivatives through irradiation by visible light to fabricate 3D constructs containing human adipose stem cells (hADSCs). The hydrogel was obtained from a solution of HA and gelatin derivatives possessing phenolic hydroxyl moieties in the presence of ruthenium(II) tris-bipyridyl dication and sodium ammonium persulfate. hADSCs enclosed in the bioprinted hydrogel construct elongated and proliferated in the hydrogel. In addition, their differentiation potential was confirmed by examining the expression of pluripotency marker genes and cell surface marker proteins, and differentiation to adipocytes in adipogenic differentiation medium. Our results demonstrate the great potential of the bioprinting method and the resultant hADSC-laden HA/gelatin constructs for applications in tissue engineering and regenerative medicine. © 2017 Wiley Periodicals, Inc.

High throughput pyrosequencing technology for molecular differential detection of Babesia vogeli, Hepatozoon canis, Ehrlichia canis and Anaplasma platys in canine blood samples.