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Sample records for atdc5 chondroprogenitors differentiating

  1. Robust Circadian Rhythm and Parathyroid Hormone-Induced Resetting during Hypertrophic Differentiation in ATDC5 Chondroprogenitor Cells.

    PubMed

    Hosokawa, Toshihiro; Tsuchiya, Yoshiki; Okubo, Naoki; Kunimoto, Tatsuya; Minami, Yoichi; Fujiwara, Hiroyoshi; Umemura, Yasuhiro; Koike, Nobuya; Kubo, Toshikazu; Yagita, Kazuhiro

    2015-12-25

    Cartilage tissues possess intrinsic circadian oscillators, which influence chondrocyte function and chondrocyte specific gene expression. However, it is not fully understood how chondrogenesis influences the circadian clock, and vice versa. Thus, we established ATDC5 cells which were stably transfected with the Bmal1:luc reporter and revealed robust circadian rhythms in ATDC5 cells during differentiation. Moreover, the circadian clock in ATDC5 cells was strongly reset by PTH in a circadian time-dependent manner. This assay system is expected to be useful for investigating the role of the circadian clock in chondrogenic differentiation and the precise molecular mechanisms underlying PTH action on the chondrocyte circadian clock.

  2. Selenoprotein O deficiencies suppress chondrogenic differentiation of ATDC5 cells.

    PubMed

    Yan, Jidong; Fei, Yao; Han, Yan; Lu, Shemin

    2016-10-01

    Selenoprotein O (Sel O) is a selenium-containing protein, but its function is still unclear. In the present study, we observed that the mRNA and protein expression levels of Sel O increased during chondrogenic induction of ATDC5 cells. The effects of Sel O on chondrocyte differentiation were then examined through shRNA-mediated gene silencing technique. The expression of Sel O was significantly suppressed at both mRNA and protein levels in a stable cell line transfected with a Sel O-specific target shRNA construct. Thereafter, we demonstrated that Sel O deficiencies suppress chondrogenic differentiation of ATDC5 cells. Sel O deficiencies inhibited expression of chondrogenic gene Sox9, Col II, and aggrecan. Sel O-deficient cells also accumulated a few cartilage glycosaminoglycans (GAGs) and decreased the activity of alkaline phosphatase (ALP). In addition, Sel O deficiencies inhibited chondrocyte proliferation through delayed cell cycle progression by suppression of cyclin D1 expression. Moreover, Sel O deficiencies induced chondrocyte death through cell apoptosis. In summary, we describe the expression patterns and the essential roles of Sel O in chondrocyte viability, proliferation, and chondrogenic differentiation. Additionally, Sel O deficiency-mediated impaired chondrogenesis may illustrate the mechanisms of Se deficiency in the pathophysiological process of the endemic osteoarthropathy.

  3. The Role of Prostaglandins and COX-Enzymes in Chondrogenic Differentiation of ATDC5 Progenitor Cells

    PubMed Central

    Caron, Marjolein M. J.; Emans, Pieter J.; Sanen, Kathleen; Surtel, Don A. M.; Cremers, Andy; Ophelders, Daan; van Rhijn, Lodewijk W.; Welting, Tim J. M.

    2016-01-01

    Objectives NSAIDs are used to relieve pain and decrease inflammation by inhibition of cyclooxygenase (COX)-catalyzed prostaglandin (PG) synthesis. PGs are fatty acid mediators involved in cartilage homeostasis, however the action of their synthesizing COX-enzymes in cartilage differentiation is not well understood. In this study we hypothesized that COX-1 and COX-2 have differential roles in chondrogenic differentiation. Methods ATDC5 cells were differentiated in the presence of COX-1 (SC-560, Mofezolac) or COX-2 (NS398, Celecoxib) specific inhibitors. Specificity of the NSAIDs and inhibition of specific prostaglandin levels were determined by EIA. Prostaglandins were added during the differentiation process. Chondrogenic outcome was determined by gene- and protein expression analyses. Results Inhibition of COX-1 prevented Col2a1 and Col10a1 expression. Inhibition of COX-2 resulted in decreased Col10a1 expression, while Col2a1 remained unaffected. To explain this difference expression patterns of both COX-enzymes as well as specific prostaglandin concentrations were determined. Both COX-enzymes are upregulated during late chondrogenic differentiation, whereas only COX-2 is briefly expressed also early in differentiation. PGD2 and PGE2 followed the COX-2 expression pattern, whereas PGF2α and TXA2 levels remained low. Furthermore, COX inhibition resulted in decreased levels of all tested PGs, except for PGD2 and PGF2α in the COX-1 inhibited condition. Addition of PGE2 and PGF2α resulted in increased expression of chondrogenic markers, whereas TXA2 increased expression of hypertrophic markers. Conclusions Our findings point towards a differential role for COX-enzymes and PG-production in chondrogenic differentiation of ATDC5 cells. Ongoing research is focusing on further elucidating the functional partition of cyclooxygenases and specific prostaglandin production. PMID:27050768

  4. Inhibition of hyaluronan synthesis alters sulfated glycosaminoglycans deposition during chondrogenic differentiation in ATDC5 cells.

    PubMed

    Yoshioka, Yutaka; Kozawa, Eiji; Urakawa, Hiroshi; Arai, Eisuke; Futamura, Naohisa; Zhuo, Lisheng; Kimata, Koji; Ishiguro, Naoki; Nishida, Yoshihiro

    2015-08-01

    In chondrogenic differentiation, expression and collaboration of specific molecules, such as aggrecan and type II collagen, in extracellular matrix (ECM) are crucial. However, few studies have clarified the roles of hyaluronan (HA) in proteoglycan aggregation during chondrogenic differentiation. We assessed the roles of HA in sulfated glycosaminoglycans deposition during chondrogenic differentiation by means of 4-methylumbelliferone (4-MU), an HA synthase inhibitor, using ATDC5 cells. ATDC5 cells were treated with 0.5 mM 4-MU for 7 or 21 days after induction of chondrogenic differentiation with insulin. Depositions of sulfated glycosaminoglycans were evaluated with Alcian blue staining. mRNA expression of ECM molecules was determined using real-time RT-PCR. The deposition of aggrecan and versican was investigated with immunohistochemical staining using specific antibodies. Effects of 4-MU on HA concentrations were analyzed by HA binding assay. 4-MU suppressed the positivity of Alcian blue staining, although this delay was reversible. Interestingly, stronger positivity of Alcian blue staining was observed at day 21 in cultures with 4-MU discontinuation than in the control. 4-MU significantly increased the mRNA expression of aggrecan, versican, and type II collagen, which was consistent with increased deposition of aggrecan and versican. The HA concentration in ECM and cell-associated region was significantly suppressed with 4-MU treatment. We conclude that the inhibition of HA synthesis slows sulfated glycosaminoglycans deposition during chondrogenic differentiation despite the increased deposition of other ECM molecules. Transient starvation of HA with 4-MU accelerates chondrogenic ECM formation, suggesting its potential to stimulate chondrogenic differentiation with adequate use.

  5. Aloe-Emodin Induces Chondrogenic Differentiation of ATDC5 Cells via MAP Kinases and BMP-2 Signaling Pathways.

    PubMed

    Yang, Ming; Li, Liang; Heo, Seok-Mo; Soh, Yunjo

    2016-07-01

    Endochondral bone formation is the process by which mesenchymal cells condense into chondrocytes, which are ultimately responsible for new bone formation. The processes of chondrogenic differentiation and hypertrophy are critical for bone formation and are therefore highly regulated. The present study was designed to investigate the effect of aloe-emodin on chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Aloe-emodin treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. ATDC5 cells were treated with aloe-emodin and stained with alcian blue. Compared with the control cells, the ATDC5 cells showed more intense alcian blue staining. This finding suggested that aloe-emodin induced the synthesis of matrix proteoglycans and increased the activity of alkaline phosphatase. Aloe-emodin also enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, BSP and RunX2 in a time-dependent manner. Furthermore, examination of the MAPK signaling pathway showed that aloe-emodin increased the activation of extracellular signal-regulated kinase (ERK), but had no effect on p38 and c-jun N-terminal kinase (JNK). Aloe-emodin also enhanced the protein expression of BMP-2 in a time-dependent manner. Thus, these results showed that aloe-emodin exhibited chodromodulating effects via the BMP-2 or ERK signaling pathway. Aloe-emodin may have potential future applications for the treatment of growth disorders. PMID:27350340

  6. Aloe-Emodin Induces Chondrogenic Differentiation of ATDC5 Cells via MAP Kinases and BMP-2 Signaling Pathways

    PubMed Central

    Yang, Ming; Li, Liang; Heo, Seok-Mo; Soh, Yunjo

    2016-01-01

    Endochondral bone formation is the process by which mesenchymal cells condense into chondrocytes, which are ultimately responsible for new bone formation. The processes of chondrogenic differentiation and hypertrophy are critical for bone formation and are therefore highly regulated. The present study was designed to investigate the effect of aloe-emodin on chondrogenic differentiation in clonal mouse chondrogenic ATDC5 cells. Aloe-emodin treatment stimulated the accumulation of cartilage nodules in a dose-dependent manner. ATDC5 cells were treated with aloe-emodin and stained with alcian blue. Compared with the control cells, the ATDC5 cells showed more intense alcian blue staining. This finding suggested that aloe-emodin induced the synthesis of matrix proteoglycans and increased the activity of alkaline phosphatase. Aloe-emodin also enhanced the expressions of chondrogenic marker genes such as collagen II, collagen X, BSP and RunX2 in a time-dependent manner. Furthermore, examination of the MAPK signaling pathway showed that aloe-emodin increased the activation of extracellular signal-regulated kinase (ERK), but had no effect on p38 and c-jun N-terminal kinase (JNK). Aloe-emodin also enhanced the protein expression of BMP-2 in a time-dependent manner. Thus, these results showed that aloe-emodin exhibited chodromodulating effects via the BMP-2 or ERK signaling pathway. Aloe-emodin may have potential future applications for the treatment of growth disorders. PMID:27350340

  7. Chondroregulatory action of prolactin on proliferation and differentiation of mouse chondrogenic ATDC5 cells in 3-dimensional micromass cultures

    SciTech Connect

    Seriwatanachai, Dutmanee; Krishnamra, Nateetip; Charoenphandhu, Narattaphol

    2012-03-30

    Highlights: Black-Right-Pointing-Pointer Mouse chondrogenic ATDC5 cells expressed PRL receptor mRNAs and proteins. Black-Right-Pointing-Pointer Low PRL concentration (10 ng/mL) increased chondrocyte viability and differentiation. Black-Right-Pointing-Pointer Higher PRL concentrations ( Greater-Than-Or-Slanted-Equal-To 100 ng/mL) decreased viability and increased apoptosis. -- Abstract: A recent investigation in lactating rats has provided evidence that the lactogenic hormone prolactin (PRL) increases endochondral bone growth and bone elongation, presumably by accelerating apoptosis of hypertrophic chondrocytes in the growth plate and/or subsequent chondrogenic matrix mineralization. Herein, we demonstrated the direct chondroregulatory action of PRL on proliferation, differentiation and apoptosis of chondrocytes in 3-dimensional micromass culture of mouse chondrogenic ATDC5 cell line. The results showed that ATDC5 cells expressed PRL receptor (PRLR) transcripts, and responded typically to PRL by downregulating PRLR expression. Exposure to a low PRL concentration of 10 ng/mL, comparable to the normal levels in male and non-pregnant female rats, increased chondrocyte viability, differentiation, proteoglycan accumulation, and mRNA expression of several chondrogenic differentiation markers, such as Sox9, ALP and Hspg2. In contrast, high PRL concentrations of Greater-Than-Or-Slanted-Equal-To 100 ng/mL, comparable to the levels in pregnancy or lactation, decreased chondrocyte viability by inducing apoptosis, with no effect on chondrogenic marker expression. It could be concluded that chondrocytes directly but differentially responded to non-pregnant and pregnant/lactating levels of PRL, thus suggesting the stimulatory effect of PRL on chondrogenesis in young growing individuals, and supporting the hypothesis of hypertrophic chondrocyte apoptosis in the growth plate of lactating rats.

  8. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line.

    PubMed

    Sato, Eiichi; Ando, Takashi; Ichikawa, Jiro; Okita, Genki; Sato, Nobutaka; Wako, Masanori; Ohba, Tetsuro; Ochiai, Satoshi; Hagino, Tetsuo; Jacobson, Richard; Haro, Hirotaka

    2014-12-01

    Osteoarthritis (OA) is a group of common, chronic, and painful inflammatory joint diseases. One important finding in OA patients is a remarkable decrease in the molecular weight of hyaluronic acid (HA) in the synovial fluid of affected joints. Therapeutic HA is available to patients in most parts of the world as a viscosupplementation product for the treatment of OA. Previous clinical reports show that high molecular weight HA (HMWHA) more effectively relieves pain than low molecular weight HA (LMWHA). However, the mechanism behind this finding remains unclear. In this study, we investigated whether a LMWHA (Low-0.9 MDa) and two types of HMWHA (High-1.9 MDa and 6 MDa) differentially affected chondroregulatory action. We tested this using ATDC5 cell, a murine chondrocytic cell line widely used in culture systems to study chondrogenic differentiation. We found that HMWHA, especially hylan G-F 20 (High-6 MDa), significantly induced aggrecan and proteoglycan accumulation, nodule formation, and mRNA expression of chondrogenic differentiation markers in a time- and dose-dependent manner. In addition, we showed that HMWHA prevented TNF-α induced inhibition of chondrogenic differentiation, with no effect on cell proliferation or viability. These results reveal that HMWHA significantly promotes chondrogenic differentiation of ATDC5 cells in vitro, and suggest that HMWHA plays a significant chondroregulatory role in vivo.

  9. BMP5 activates multiple signaling pathways and promotes chondrogenic differentiation in the ATDC5 growth plate model.

    PubMed

    Snelling, Sarah J B; Hulley, Philippa A; Loughlin, John

    2010-08-01

    The bone morphogenetic protein 5 (BMP5) participates in skeletal development but its direct effects on the function of growth plate chondrocytes during chondrogenesis have not been explored. We have investigated the signaling pathways activated by BMP5 and its effect on chondrogenic differentiation in the ATDC5 growth plate chondrocyte model. BMP5 transiently activated p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinase signaling after 10 days of differentiation; sustained Smad and p38 MAPK signaling were seen after 15 days differentiation. All three pathways were activated by BMP5 in human adult articular chondrocytes. BMP5 alone and in combination with the chondrogenic enhancer, insulin, induced proteoglycan synthesis, aggrecan core protein 1 expression, and alkaline phosphatase activity. Upregulation of hypertrophic markers parathyroid receptor 1 and collagen type X alpha 1 occurred in BMP5-treated ATDC5 cultures. BMP5 is clearly chondrogenic and exhibits stage-specific regulation of multiple signaling pathways in this growth plate model. In particular, BMP5 accelerates expression of hypertrophy markers which is of relevance in both development and diseases such as osteoarthritis.

  10. Matrilin-3 Chondrodysplasia Mutations Cause Attenuated Chondrogenesis, Premature Hypertrophy and Aberrant Response to TGF-β in Chondroprogenitor Cells

    PubMed Central

    Jayasuriya, Chathuraka T.; Zhou, Fiona H.; Pei, Ming; Wang, Zhengke; Lemme, Nicholas J.; Haines, Paul; Chen, Qian

    2014-01-01

    Studies have shown that mutations in the matrilin-3 gene (MATN3) are associated with multiple epiphyseal dysplasia (MED) and spondyloepimetaphyseal dysplasia (SEMD). We tested whether MATN3 mutations affect the differentiation of chondroprogenitor and/or mesenchymal stem cells, which are precursors to chondrocytes. ATDC5 chondroprogenitors stably expressing wild-type (WT) MATN3 underwent spontaneous chondrogenesis. Expression of chondrogenic markers collagen II and aggrecan was inhibited in chondroprogenitors carrying the MED or SEMD MATN3 mutations. Hypertrophic marker collagen X remained attenuated in WT MATN3 chondroprogenitors, whereas its expression was elevated in chondroprogenitors expressing the MED or SEMD mutant MATN3 gene suggesting that these mutations inhibit chondrogenesis but promote hypertrophy. TGF-β treatment failed to rescue chondrogenesis markers but dramatically increased collagen X mRNA expression in mutant MATN3 expressing chondroprogenitors. Synovium derived mesenchymal stem cells harboring the SEMD mutation exhibited lower glycosaminoglycan content than those of WT MATN3 in response to TGF-β. Our results suggest that the properties of progenitor cells harboring MATN3 chondrodysplasia mutations were altered, as evidenced by attenuated chondrogenesis and premature hypertrophy. TGF-β treatment failed to completely rescue chondrogenesis but instead induced hypertrophy in mutant MATN3 chondroprogenitors. Our data suggest that chondroprogenitor cells should be considered as a potential target of chondrodysplasia therapy. PMID:25196597

  11. Biological and Chemical Removal of Primary Cilia Affects Mechanical Activation of Chondrogenesis Markers in Chondroprogenitors and Hypertrophic Chondrocytes

    PubMed Central

    Deren, Matthew E.; Yang, Xu; Guan, Yingjie; Chen, Qian

    2016-01-01

    Chondroprogenitors and hypertrophic chondrocytes, which are the first and last stages of the chondrocyte differentiation process, respectively, are sensitive to mechanical signals. We hypothesize that the mechanical sensitivity of these cells depends on the cell surface primary cilia. To test this hypothesis, we removed the primary cilia by biological means with transfection with intraflagellar transport protein 88 (IFT88) siRNA or by chemical means with chloral hydrate treatment. Transfection of IFT88 siRNA significantly reduced the percentage of ciliated cells in both chondroprogenitor ATDC5 cells as well as primary hypertrophic chondrocytes. Cyclic loading (1 Hz, 10% matrix deformation) of ATDC5 cells in three-dimensional (3D) culture stimulates the mRNA levels of chondrogenesis marker Type II collagen (Col II), hypertrophic chondrocyte marker Type X collagen (Col X), and a molecular regulator of chondrogenesis and chondrocyte hypertrophy bone morphogenetic protein 2 (BMP-2). The reduction of ciliated chondroprogenitors abolishes mechanical stimulation of Col II, Col X, and BMP-2. In contrast, cyclic loading stimulates Col X mRNA levels in hypertrophic chondrocytes, but not those of Col II and BMP-2. Both biological and chemical reduction of ciliated hypertrophic chondrocytes reduced but failed to abolish mechanical stimulation of Col X mRNA levels. Thus, primary cilia play a major role in mechanical stimulation of chondrogenesis and chondrocyte hypertrophy in chondroprogenitor cells and at least a partial role in hypertrophic chondrocytes. PMID:26861287

  12. Tumour necrosis factor-alpha up-regulates the expression of BMP-4 mRNA but inhibits chondrogenesis in mouse clonal chondrogenic EC cells, ATDC5.

    PubMed

    Horiguchi, M; Akiyama, H; Ito, H; Shigeno, C; Nakamura, T

    2000-05-01

    Tumour necrosis factor (TNF)-alpha causes the degradation of articular cartilage in arthritis via direct actions on chondrocytes. However, it remains unknown whether TNF-alpha affects chondrogenesis in chondroprogenitors. In the present study, we assessed the effects of TNF-alpha in vitro on chondrogenesis using mouse clonal chondrogenic EC cells, ATDC5. TNF-alpha (10 ng/ml) stimulated [3H] thymidine incorporation in undifferentiated ATDC5 cells, and suppressed cartilaginous nodule formation and the accumulation of cartilage-specific proteoglycan. We recently showed that undifferentiated ATDC5 cells express BMP-4 and that exogenously administered BMP-4 promotes chondrogenesis in these cells. Interestingly, TNF-alpha up-regulated the expression of BMP-4 mRNA in undifferentiated ATDC5 cells in time- and dose-dependent manners. However, exogenously administered BMP-4 was not capable of reversing the inhibitory action of TNF-alpha on chondrogenesis in ATDC5 cells. These results indicate that TNF-alpha stimulates both cell proliferation and BMP-4 expression but inhibits chondrogenesis in chondroprogenitor-like ATDC5 cells. PMID:10857772

  13. The Importance of Connexin Hemichannels During Chondroprogenitor Cell Differentiation in Hydrogel Versus Microtissue Culture Models

    PubMed Central

    Schrobback, Karsten; Klein, Travis Jacob

    2015-01-01

    Appropriate selection of scaffold architecture is a key challenge in cartilage tissue engineering. Gap junction-mediated intercellular contacts play important roles in precartilage condensation of mesenchymal cells. However, scaffold architecture could potentially restrict cell–cell communication and differentiation. This is particularly important when choosing the appropriate culture platform as well as scaffold-based strategy for clinical translation, that is, hydrogel or microtissues, for investigating differentiation of chondroprogenitor cells in cartilage tissue engineering. We, therefore, studied the influence of gap junction-mediated cell–cell communication on chondrogenesis of bone marrow-derived mesenchymal stromal cells (BM-MSCs) and articular chondrocytes. Expanded human chondrocytes and BM-MSCs were either (re-) differentiated in micromass cell pellets or encapsulated as isolated cells in alginate hydrogels. Samples were treated with and without the gap junction inhibitor 18-α glycyrrhetinic acid (18αGCA). DNA and glycosaminoglycan (GAG) content and gene expression levels (collagen I/II/X, aggrecan, and connexin 43) were quantified at various time points. Protein localization was determined using immunofluorescence, and adenosine-5′-triphosphate (ATP) was measured in conditioned media. While GAG/DNA was higher in alginate compared with pellets for chondrocytes, there were no differences in chondrogenic gene expression between culture models. Gap junction blocking reduced collagen II and extracellular ATP in all chondrocyte cultures and in BM-MSC hydrogels. However, differentiation capacity was not abolished completely by 18αGCA. Connexin 43 levels were high throughout chondrocyte cultures and peaked only later during BM-MSC differentiation, consistent with the delayed response of BM-MSCs to 18αGCA. Alginate hydrogels and microtissues are equally suited culture platforms for the chondrogenic (re-)differentiation of expanded human articular

  14. Efficient differentiation of human iPSC-derived mesenchymal stem cells to chondroprogenitor cells.

    PubMed

    Guzzo, Rosa M; Gibson, Jason; Xu, Ren-He; Lee, Francis Y; Drissi, Hicham

    2013-02-01

    Induced pluripotent stem cells (iPSC) hold tremendous potential for personalized cell-based repair strategies to treat musculoskeletal disorders. To establish human iPSCs as a potential source of viable chondroprogenitors for articular cartilage repair, we assessed the in vitro chondrogenic potential of the pluripotent population versus an iPSC-derived mesenchymal-like progenitor population. We found the direct plating of undifferentiated iPSCs into high-density micromass cultures in the presence of BMP-2 promoted chondrogenic differentiation, however these conditions resulted in a mixed population of cells resembling the phenotype of articular cartilage, transient cartilage, and fibrocartilage. The progenitor cells derived from human iPSCs exhibited immunophenotypic features of mesenchymal stem cells (MSCs) and developed along multiple mesenchymal lineages, including osteoblasts, adipocytes, and chondrocytes in vitro. The data indicate the derivation of a mesenchymal stem cell population from human iPSCs is necessary to limit culture heterogeneity as well as chondrocyte maturation in the differentiated progeny. Moreover, as compared to pellet culture differentiation, BMP-2 treatment of iPSC-derived MSC-like (iPSC-MSC) micromass cultures resulted in a phenotype more typical of articular chondrocytes, characterized by the enrichment of cartilage-specific type II collagen (Col2a1), decreased expression of type I collagen (Col1a1) as well as lack of chondrocyte hypertrophy. These studies represent a first step toward identifying the most suitable iPSC progeny for developing cell-based approaches to repair joint cartilage damage. PMID:22961870

  15. Human YKL39 (chitinase 3-like protein 2), an osteoarthritis-associated gene, enhances proliferation and type II collagen expression in ATDC5 cells

    SciTech Connect

    Miyatake, Kazumasa; Tsuji, Kunikazu; Yamaga, Mika; Yamada, Jun; Matsukura, Yu; Abula, Kahaer; Sekiya, Ichiro; Muneta, Takeshi

    2013-02-01

    Highlights: ► hYKL-39 expression is increased in osteoarthritic articular chondrocytes. ► To examine the molecular functions of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in chondrocytic ATDC5 cells. ► hYKL-39 enhanced proliferation and colony formation in ATDC5 cells. ► hYKL-39 increased type II collagen expression in ATDC5 cells treated with chondrogenic medium. -- Abstract: Human YKL39 (chitinase 3-like protein 2/CHI3L2) is a secreted 39 kDa protein produced by articular chondrocytes and synoviocytes. Recent studies showed that hYKL-39 expression is increased in osteoarthritic articular chondrocytes suggesting the involvement of hYKL-39 in the progression of osteoarthritis (OA). However little is known regarding the molecular function of hYKL-39 in joint homeostasis. Sequence analyses indicated that hYKL-39 has significant identity with the human chitotorisidase family molecules, although it is considered that hYKL-39 has no enzymatic activity since it lacks putative chitinase catalytic motif. In this study, to examine the molecular function of hYKL-39 in chondrocytes, we overexpressed hYKL-39 in ATDC5 cells. Here we report that hYKL-39 enhances colony forming activity, cell proliferation, and type II collagen expression in these cells. These data suggest that hYKL-39 is a novel growth and differentiation factor involved in cartilage homeostasis.

  16. Interleukin-1beta induces death in chondrocyte-like ATDC5 cells through mitochondrial dysfunction and energy depletion in a reactive nitrogen and oxygen species-dependent manner.

    PubMed

    Yasuhara, Rika; Miyamoto, Yoichi; Akaike, Takaaki; Akuta, Teruo; Nakamura, Masanori; Takami, Masamichi; Morimura, Naoko; Yasu, Kayoko; Kamijo, Ryutaro

    2005-07-15

    IL-1 (interleukin-1) acts as a key mediator of the degeneration of articular cartilage in RA (rheumatoid arthritis) and OA (osteoarthritis),where chondrocyte death is observed. It is still controversial, however, whether IL-1 induces chondrocyte death. In the present study, the viability of mouse chondrocyte-like ATDC5 cells was reduced by the treatment with IL-1beta for 48 h or longer. IL-1beta augmented the expression of the catalytic gp91 subunit of NADPH oxidase, gp91phox, as well as inducible NO synthase in ATDC5 cells. Generation of nitrated guanosine and tyrosine suggested the formation of reactive nitrogen species including ONOO- (peroxynitrite), a reaction product of NO and O2-, in ATDC5 cells and rat primary chondrocytes treated with IL-1beta. Death of ATDC5 cells after IL-1beta treatment was prevented by an NADPH-oxidase inhibitor, AEBSF[4-(2-aminoethyl)benzene-sulphonyl fluoride], an NO synthase inhibitor, L-NAME (NG-nitro-L-arginine methyl ester), and a ONOO- scavenger, uric acid. The viability of ATDC5 cells was reduced by the ONOO(-)-generator 3-(4-morpholinyl)sydnonimine hydrochloride, but not by either the NO-donor 1-hydroxy-2-oxo-3-(N-methyl-2-aminopropyl)-3-methyl-1-triazene or S-nitrosoglutathione. Disruption of mitochondrial membrane potential and ATP deprivation were observed in IL-1beta-treated ATDC5 cells, both of which were restored by L-NAME, AEBSF or uric acid. On the other hand, no morphological or biochemical signs indicating apoptosis were observed in these cells. These results suggest that the death of chondrocyte-like ATDC5 cells was mediated at least in part by mitochondrial dysfunction and energy depletion through ONOO- formation after IL-1beta treatment. PMID:15784009

  17. Mesenchymal chondroprogenitor cell origin and therapeutic potential.

    PubMed

    O'Sullivan, Janice; D'Arcy, Sinéad; Barry, Frank P; Murphy, J Mary; Coleman, Cynthia M

    2011-01-01

    Mesenchymal progenitor cells, a multipotent adult stem cell population, have the ability to differentiate into cells of connective tissue lineages, including fat, cartilage, bone and muscle, and therefore generate a great deal of interest for their potential use in regenerative medicine. During development, endochondral bone is formed from a template of cartilage that transforms into bone; however, mature articular cartilage remains in the articulating joints, where its principal role is reducing friction and dispersing mechanical load. Articular cartilage is prone to damage from sports injuries or ageing, which regularly progresses to more serious joint disorders, such as osteoarthritis. Osteoarthritis is a degenerative joint disease characterized by the thinning and eventual wearing of articular cartilage, and affects millions of people worldwide. Due to low chondrocyte motility and proliferative rates, and complicated by the absence of blood vessels, cartilage has a limited ability to self-repair. Current pharmaceutical and surgical interventions fail to generate repair tissue with the mechanical and cellular properties of native host cartilage. The long-term success of cartilage repair will therefore depend on regenerative methodologies resulting in the restoration of articular cartilage that closely duplicates the native tissue. For cell-based therapies, the optimal cell source must be readily accessible with easily isolated, abundant cells capable of collagen type II and sulfated proteoglycan production in appropriate proportions. Although a cell source with these therapeutic properties remains elusive, mesenchymal chondroprogenitors retain their expansion capacity with the promise of reproducing the structural or biomechanical properties of healthy articular cartilage. As current knowledge regarding chondroprogenitors is relatively limited, this review will focus on their origin and therapeutic application. PMID:21371355

  18. CD146 as a new marker for an increased chondroprogenitor cell sub-population in the later stages of osteoarthritis.

    PubMed

    Su, Xinlin; Zuo, Wei; Wu, Zhihong; Chen, Jun; Wu, Nan; Ma, Pei; Xia, Zenan; Jiang, Chao; Ye, Zixing; Liu, Sen; Liu, Jiaqi; Zhou, Guangqian; Wan, Chao; Qiu, Guixing

    2015-01-01

    Cartilage-derived mesenchymal stem cells (MSCs) have been isolated with different methods. In this study lateral and medial femoral condyles were respectively collected from patients with late-stage osteoarthritis during the total knee arthroplasty. After digestion of the cartilage tissues with type II collagenase and analysis by fluorescence-activated cell sorting (FACS) with CD146, a chondroprogenitor cell sub-population were isolated and purified. The expression of other MSC-associated markers in the CD146+ chondroprogenitors was analyzed by flow cytometry. Multi-lineage differentiation capacity of CD146+ chondroprogenitors was compared with that of unsorted chondrocytes and adipose-derived MSCs (ADMSCs). Higher percentage of CD146+ chondroprogenitors isolated from the medial femoral condyles was observed than that from the lateral. CD146+ chondroprogenitors expressed high levels of MSC-specific surface antigens, and showed higher chondrogenesis capacity than ADMSCs and unsorted chondrocytes in a 3D cell pellet culture model. Thus CD146 might be a new cell surface marker for cartilage progenitor cell population in the late-stage osteoarthritis. PMID:25266708

  19. Transforming growth factor-{beta}1 regulates fibronectin isoform expression and splicing factor SRp40 expression during ATDC5 chondrogenic maturation

    SciTech Connect

    Han Fei; Gilbert, James R.; Harrison, Gerald; Adams, Christopher S.; Freeman, Theresa; Tao Zhuliang; Zaka, Raihana; Liang Hongyan; Williams, Charlene; Tuan, Rocky S.; Norton, Pamela A.; Hickok, Noreen J. . E-mail: Noreen.Hickok@jefferson.edu

    2007-05-01

    Fibronectin (FN) isoform expression is altered during chondrocyte commitment and maturation, with cartilage favoring expression of FN isoforms that includes the type II repeat extra domain B (EDB) but excludes extra domain A (EDA). We and others have hypothesized that the regulated splicing of FN mRNAs is necessary for the progression of chondrogenesis. To test this, we treated the pre-chondrogenic cell line ATDC5 with transforming growth factor-{beta}1, which has been shown to modulate expression of the EDA and EDB exons, as well as the late markers of chondrocyte maturation; it also slightly accelerates the early acquisition of a sulfated proteoglycan matrix without affecting cell proliferation. When chondrocytes are treated with TGF-{beta}1, the EDA exon is preferentially excluded at all times whereas the EDB exon is relatively depleted at early times. This regulated alternative splicing of FN correlates with the regulation of alternative splicing of SRp40, a splicing factor facilitating inclusion of the EDA exon. To determine if overexpression of the SRp40 isoforms altered FN and FN EDA organization, cDNAs encoding these isoforms were overexpressed in ATDC5 cells. Overexpression of the long-form of SRp40 yielded an FN organization similar to TGF-{beta}1 treatment; whereas overexpression of the short form of SRp40 (which facilitates EDA inclusion) increased formation of long-thick FN fibrils. Therefore, we conclude that the effects of TGF-{beta}1 on FN splicing during chondrogenesis may be largely dependent on its effect on SRp40 isoform expression.

  20. Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy

    PubMed Central

    Jayasuriya, Chathuraka T.

    2016-01-01

    Chondroprogenitor cells are a subpopulation of multipotent progenitors that are primed for chondrogenesis. They are believed to have the biological repertoire to be ideal for cell-based cartilage therapy. In addition to summarizing recent advances in chondroprogenitor cell characterization, this review discusses the projected pros and cons of utilizing chondroprogenitors in regenerative medicine and compares them to that of preexisting methods, including autologous chondrocyte implantation (ACI) and the utilization of bone marrow derived mesenchymal stem cells (MSCs) for the purpose of cartilage tissue repair. PMID:26075411

  1. Potential benefits and limitations of utilizing chondroprogenitors in cell-based cartilage therapy.

    PubMed

    Jayasuriya, Chathuraka T; Chen, Qian

    2015-01-01

    Chondroprogenitor cells are a subpopulation of multipotent progenitors that are primed for chondrogenesis. They are believed to have the biological repertoire to be ideal for cell-based cartilage therapy. In addition to summarizing recent advances in chondroprogenitor cell characterization, this review discusses the projected pros and cons of utilizing chondroprogenitors in regenerative medicine and compares them with that of pre-existing methods, including autologous chondrocyte implantation (ACI) and the utilization of bone marrow derived mesenchymal stem cells (MSCs) for the purpose of cartilage tissue repair.

  2. Cartilage Repair Using Human Embryonic Stem Cell-Derived Chondroprogenitors

    PubMed Central

    Kapacee, Zoher; Peng, Jiang; Lu, Shibi; Lucas, Robert J.; Hardingham, Timothy E.

    2014-01-01

    In initial work, we developed a 14-day culture protocol under potential GMP, chemically defined conditions to generate chondroprogenitors from human embryonic stem cells (hESCs). The present study was undertaken to investigate the cartilage repair capacity of these cells. The chondrogenic protocol was optimized and validated with gene expression profiling. The protocol was also applied successfully to two lines of induced pluripotent stem cells (iPSCs). Chondrogenic cells derived from hESCs were encapsulated in fibrin gel and implanted in osteochondral defects in the patella groove of nude rats, and cartilage repair was evaluated by histomorphology and immunocytochemistry. Genes associated with chondrogenesis were upregulated during the protocol, and pluripotency-related genes were downregulated. Aggregation of chondrogenic cells was accompanied by high expression of SOX9 and strong staining with Safranin O. Culture with PluriSln1 was lethal for hESCs but was tolerated by hESC chondrogenic cells, and no OCT4-positive cells were detected in hESC chondrogenic cells. iPSCs were also shown to generate chondroprogenitors in this protocol. Repaired tissue in the defect area implanted with hESC-derived chondrogenic cells was stained for collagen II with little collagen I, but negligible collagen II was observed in the fibrin-only controls. Viable human cells were detected in the repair tissue at 12 weeks. The results show that chondrogenic cells derived from hESCs, using a chemically defined culture system, when implanted in focal defects were able to promote cartilage repair. This is a first step in evaluating these cells for clinical application for the treatment of cartilage lesions. PMID:25273540

  3. Epiphyseal Chondroprogenitors Provide a Stable Cell Source for Cartilage Cell Therapy

    PubMed Central

    Darwiche, Salim; Scaletta, Corinne; Raffoul, Wassim; Pioletti, Dominique P.; Applegate, Lee Ann

    2012-01-01

    Articular cartilage regeneration poses particularly tough challenges for implementing cell-based therapies. Many cell types have been investigated looking for a balanced combination of responsiveness and stability, yet techniques are still far from defining a gold standard. The work presented focuses on the reliable expansion and characterization of a clinical grade human epiphyseal chondroprogenitor (ECP) cell bank from a single tissue donation. A parental human ECP cell bank was established, which provides the seed material for master and working cell banks. ECPs were investigated at both low and high cumulative population doublings looking at morphology, monolayer expansion kinetics, resistance to cryogenic shock, colony-forming efficiency, and cell surface markers. Three-dimensional micropellet assays were used to determine spontaneous extracellular matrix deposition at varying population doublings and monolayer 2D differentiation studies were undertaken to assess the propensity for commitment into other lineages and their stability. ECPs exhibited remarkable homogeneity in expansion with a steady proliferative potential averaging three population doublings over 8 days. Surface marker analysis revealed no detectable contaminating subpopulations or population enrichment during prolonged culture periods. Despite a slight reduction in Sox9 expression levels at higher population doublings in monolayer, nuclear localization was equivalent both in monolayer and in micropellet format. Equally, ECPs were capable of depositing glycosaminoglycans and producing aggrecan, collagen I, and collagen II in 3D pellets both at low and high population doublings indicating a stable spontaneous chondrogenic potential. Osteogenic induction was differentially restricted in low and high population doublings as observed by Von Kossa staining of calcified matrix, with a notable collagen X, MMP13, and ADAMTS5 downregulation. Rare adipogenic induction was seen as evidenced by cytoplasmic

  4. Epiphyseal Chondroprogenitors Provide a Stable Cell Source for Cartilage Cell Therapy.

    PubMed

    Darwiche, Salim; Scaletta, Corinne; Raffoul, Wassim; Pioletti, Dominique P; Applegate, Lee Ann

    2012-01-01

    Articular cartilage regeneration poses particularly tough challenges for implementing cell-based therapies. Many cell types have been investigated looking for a balanced combination of responsiveness and stability, yet techniques are still far from defining a gold standard. The work presented focuses on the reliable expansion and characterization of a clinical grade human epiphyseal chondroprogenitor (ECP) cell bank from a single tissue donation. A parental human ECP cell bank was established, which provides the seed material for master and working cell banks. ECPs were investigated at both low and high cumulative population doublings looking at morphology, monolayer expansion kinetics, resistance to cryogenic shock, colony-forming efficiency, and cell surface markers. Three-dimensional micropellet assays were used to determine spontaneous extracellular matrix deposition at varying population doublings and monolayer 2D differentiation studies were undertaken to assess the propensity for commitment into other lineages and their stability. ECPs exhibited remarkable homogeneity in expansion with a steady proliferative potential averaging three population doublings over 8 days. Surface marker analysis revealed no detectable contaminating subpopulations or population enrichment during prolonged culture periods. Despite a slight reduction in Sox9 expression levels at higher population doublings in monolayer, nuclear localization was equivalent both in monolayer and in micropellet format. Equally, ECPs were capable of depositing glycosaminoglycans and producing aggrecan, collagen I, and collagen II in 3D pellets both at low and high population doublings indicating a stable spontaneous chondrogenic potential. Osteogenic induction was differentially restricted in low and high population doublings as observed by Von Kossa staining of calcified matrix, with a notable collagen X, MMP13, and ADAMTS5 downregulation. Rare adipogenic induction was seen as evidenced by cytoplasmic

  5. Combining Freshly Isolated Chondroprogenitor Cells from the Infrapatellar Fat Pad with a Growth Factor Delivery Hydrogel as a Putative Single Stage Therapy for Articular Cartilage Repair

    PubMed Central

    Ahearne, Mark; Liu, Yurong

    2014-01-01

    Growth factor delivery systems incorporating chondroprogenitor cells are an attractive potential treatment option for damaged cartilage. The rapid isolation, processing, and implantation of therapeutically relevant numbers of autologous chondroprogenitor cells, all performed “in-theatre” during a single surgical procedure, would significantly accelerate the clinical translation of such tissue engineered implants by avoiding the time, financial and regulatory challenges associated with in vitro cell expansion, and differentiation. The first objective of this study was to explore if rapid adherence to a specific substrate could be used as a simple means to quickly identify a subpopulation of chondroprogenitor cells from freshly digested infrapatellar fat pad (IFP) tissue. Adhesion of cells to tissue culture plastic within 30 min was examined as a mechanism of isolating subpopulations of cells from the freshly digested IFP. CD90, a cell surface marker associated with cell adhesion, was found to be more highly expressed in rapidly adhering cells (termed “RA” cells) compared to those that did not adhere (termed “NA” cells) in this timeframe. The NA subpopulation contained a lower number of colony forming cells, but overall had a greater chondrogenic potential but a diminished osteogenic potential compared to the RA subpopulation and unmanipulated freshly isolated (FI) control cells. When cultured in agarose hydrogels, NA cells proliferated faster than RA cells, accumulating significantly higher amounts of total sGAG and collagen. Finally, we sought to determine if cartilage tissue could be engineered by seeding such FI cells into a transforming growth factor-β3 delivery hydrogel. In such a system, both RA and NA cell populations demonstrated an ability to proliferate and produced a matrix rich in sGAG (∼2% w/w) that stained positively for type II collagen; however, the tissues were comparable to that generated using FI cells. Therefore, while the

  6. Articular Chondroprogenitor Cells Maintain Chondrogenic Potential but Fail to Form a Functional Matrix When Implanted Into Muscles of SCID Mice

    PubMed Central

    De Bari, Cosimo; Dell’Accio, Francesco; Archer, Charles W.

    2014-01-01

    Objective Articular cartilage is a complex tissue comprising phenotypically distinct zones. Research has identified the presence of a progenitor cell population in the surface zone of immature articular cartilage. The aim of the present study was to determine the in vivo plasticity of articular cartilage progenitor. Design Chondropogenitor cells were isolated from bovine metacarpalphalangeal joints by differential adhesion to fibronectin. Cells were labeled with PKH26 and injected into the thigh muscle of severe-combined immunodeficient (SCID) mice. After 2 weeks, the muscles were dissected and cryosectioned. Sections were stained with safranin O and labeled for sox9 and collagen type II. Polymerase chain reaction analysis was carried out to determine plasticity for a number of tissue-specific markers. Full-depth chondrocytes acted as a control. Results Fluorescent PKH26 labeled cells were detected after 2 weeks in all samples analyzed. A cartilage pellet was present after injection of freshly isolated chondrocytes. After injection with clonal and enriched populations of chondroprogenitors, no distinct pellet was detected, but diffuse cartilage nodules were found with regions of safranin O staining and Sox9. Low levels of collagen type II were also detected. Polymerase chain reaction analysis identified the presence of the endothelial cell marker PECAM-1 in one clonal cell line, demonstrating phenotypic plasticity into the phenotype of the surrounding host tissues. Conclusions The bovine articular cartilage progenitor cells were able to survive in vivo postimplantation, but failed to create a robust cartilage pellet, despite expressing sox9 and type II collagen. This suggests the cells require further signals for chondrogenic differentiation. PMID:26069702

  7. TASR-1 regulates alternative splicing of collagen genes in chondrogenic cells.

    PubMed

    Matsushita, Hiroshi; Blackburn, Michael L; Klineberg, Eric; Zielinska-Kwiatkowska, Anna; Bolander, Mark E; Sarkar, Gobinda; Suva, Larry J; Chansky, Howard A; Yang, Liu

    2007-05-01

    During the differentiation of chondroprogenitors into mature chondrocytes, the alternative splicing of collagen genes switches from longer isoforms to shorter ones. To investigate the underlying mechanisms, we infected mouse ATDC5 chondroprogenitor cells with retrovirus for stable expression of two closely related SR splicing factors. RT-PCR analysis revealed that TASR-1, but not TASR-2, influenced alternative splicing of type II and type XI collagens in ATDC5 cells. The effect of TASR-1 on splicing could be reversed with the addition of insulin. Results from our microarray analysis of ATDC5 cells showed that TASR-1 and TASR-2 differentially affect genes involved in the differentiation of chondrocytes. Of special interest is the finding that TASR-1 could down-regulate expression of type X collagen, a hallmark of hypertrophic chondrocytes. Immunohistostaining demonstrated that TASR-1 protein is more abundantly expressed than TASR-2 in mouse articular chondrocytes, raising the possibility that TASR-1 might be involved in phenotype maintenance of articular chondrocytes. PMID:17367759

  8. TASR-1 regulates alternative splicing of collagen genes in chondrogenic cells.

    PubMed

    Matsushita, Hiroshi; Blackburn, Michael L; Klineberg, Eric; Zielinska-Kwiatkowska, Anna; Bolander, Mark E; Sarkar, Gobinda; Suva, Larry J; Chansky, Howard A; Yang, Liu

    2007-05-01

    During the differentiation of chondroprogenitors into mature chondrocytes, the alternative splicing of collagen genes switches from longer isoforms to shorter ones. To investigate the underlying mechanisms, we infected mouse ATDC5 chondroprogenitor cells with retrovirus for stable expression of two closely related SR splicing factors. RT-PCR analysis revealed that TASR-1, but not TASR-2, influenced alternative splicing of type II and type XI collagens in ATDC5 cells. The effect of TASR-1 on splicing could be reversed with the addition of insulin. Results from our microarray analysis of ATDC5 cells showed that TASR-1 and TASR-2 differentially affect genes involved in the differentiation of chondrocytes. Of special interest is the finding that TASR-1 could down-regulate expression of type X collagen, a hallmark of hypertrophic chondrocytes. Immunohistostaining demonstrated that TASR-1 protein is more abundantly expressed than TASR-2 in mouse articular chondrocytes, raising the possibility that TASR-1 might be involved in phenotype maintenance of articular chondrocytes.

  9. Osteo-chondroprogenitor-specific deletion of the selenocysteine tRNA gene, Trsp, leads to chondronecrosis and abnormal skeletal development: a putative model for Kashin-Beck disease.

    PubMed

    Downey, Charlene M; Horton, Chelsea R; Carlson, Bradley A; Parsons, Trish E; Hatfield, Dolph L; Hallgrímsson, Benedikt; Jirik, Frank R

    2009-08-01

    Kashin-Beck disease, a syndrome characterized by short stature, skeletal deformities, and arthropathy of multiple joints, is highly prevalent in specific regions of Asia. The disease has been postulated to result from a combination of different environmental factors, including contamination of barley by mold mycotoxins, iodine deficiency, presence of humic substances in drinking water, and, importantly, deficiency of selenium. This multifunctional trace element, in the form of selenocysteine, is essential for normal selenoprotein function, including attenuation of excessive oxidative stress, and for the control of redox-sensitive molecules involved in cell growth and differentiation. To investigate the effects of skeletal selenoprotein deficiency, a Cre recombinase transgenic mouse line was used to trigger Trsp gene deletions in osteo-chondroprogenitors. Trsp encodes selenocysteine tRNA([Ser]Sec), required for the incorporation of selenocysteine residues into selenoproteins. The mutant mice exhibited growth retardation, epiphyseal growth plate abnormalities, and delayed skeletal ossification, as well as marked chondronecrosis of articular, auricular, and tracheal cartilages. Phenotypically, the mice thus replicated a number of the pathological features of Kashin-Beck disease, supporting the notion that selenium deficiency is important to the development of this syndrome. PMID:19696890

  10. Effect of Fibroblast Growth Factor 2 on Equine Synovial Fluid Chondroprogenitor Expansion and Chondrogenesis

    PubMed Central

    Bianchessi, Marta; Chen, Yuwen; Durgam, Sushmitha; Pondenis, Holly; Stewart, Matthew

    2016-01-01

    Mesenchymal stem cells have been identified in the synovial fluid of several species. This study was conducted to characterize chondroprogenitor (CP) cells in equine synovial fluid (SF) and to determine the effect of fibroblast growth factor 2 (FGF-2) on SF-CP monolayer proliferation and subsequent chondrogenesis. We hypothesized that FGF-2 would stimulate SF-CP proliferation and postexpansion chondrogenesis. SF aspirates were collected from adult equine joints. Colony-forming unit (CFU) assays were performed during primary cultures. At first passage, SF-cells were seeded at low density, with or without FGF-2. Following monolayer expansion and serial immunophenotyping, cells were transferred to chondrogenic pellet cultures. Pellets were analyzed for chondrogenic mRNA expression and cartilage matrix secretion. There was a mean of 59.2 CFU/mL of SF. FGF-2 increased the number of population doublings during two monolayer passages and halved the population doubling times. FGF-2 did not alter the immunophenotype of SF-CPs during monolayer expansion, nor did FGF-2 compromise chondrogenesis. Hypertrophic phenotypic markers were not expressed in control or FGF-2 groups. FGF-2 did prevent the development of a “fibroblastic” cell layer around pellet periphery. FGF-2 significantly accelerates in vitro SF-CP expansion, the major hurdle to clinical application of this cell population, without detrimentally affecting subsequent chondrogenic capacity. PMID:26839571

  11. Constitutive E2F1 Overexpression Delays Endochondral Bone Formation by Inhibiting Chondrocyte Differentiation

    PubMed Central

    Scheijen, Blanca; Bronk, Marieke; van der Meer, Tiffany; Bernards, René

    2003-01-01

    Longitudinal bone growth results from endochondral ossification, a process that requires proliferation and differentiation of chondrocytes. It has been shown that proper endochondral bone formation is critically dependent on the retinoblastoma family members p107 and p130. However, the precise functional roles played by individual E2F proteins remain poorly understood. Using both constitutive and conditional E2F1 transgenic mice, we show that ubiquitous transgene-driven expression of E2F1 during embryonic development results in a dwarf phenotype and significantly reduced postnatal viability. Overexpression of E2F1 disturbs chondrocyte maturation, resulting in delayed endochondral ossification, which is characterized by reduced hypertrophic zones and disorganized growth plates. Employing the chondrogenic cell line ATDC5, we investigated the effects of enforced E2F expression on the different phases of chondrocyte maturation that are normally required for endochondral ossification. Ectopic E2F1 expression strongly inhibits early- and late-phase differentiation of ATDC5 cells, accompanied by diminished cartilage nodule formation as well as decreased type II collagen, type X collagen, and aggrecan gene expression. In contrast, overexpression of E2F2 or E2F3a results in only a marginal delay of chondrocyte maturation, and increased E2F4 levels have no effect. These data are consistent with the notion that E2F1 is a regulator of chondrocyte differentiation. PMID:12724423

  12. Serum of patients with active rheumatoid arthritis inhibits differentiation of osteochondrogenic precursor cells.

    PubMed

    Pathak, Janak L; Verschueren, Patrick; Lems, Willem F; Bravenboer, Nathalie; Klein-Nulend, Jenneke; Bakker, Astrid D; Luyten, Frank P

    2016-05-01

    Delayed fracture healing is frequently experienced in patients with systemic inflammation such as during rheumatoid arthritis (RA). The reasons for this are diverse, but could also be caused by inflammatory cytokines and/or growth factors in serum from patients with active disease. We hypothesized that serum from patients with active RA contains circulating inflammatory factors that inhibit differentiation of osteochondrogenic precursors. Serum was obtained from 15 patients with active RA (active RA-sera) and from the same patients in clinical remission 1 year later (remission RA-sera; controls). The effect of active RA-sera on osteochondrogenic differentiation of chondrogenic ATDC5 cells and primary human periosteum-derived progenitor cells (HPDC) was determined in micromass culture. In ATDC5 cells, active RA-sera reduced Ki67 transcription levels by 40% and cartilage matrix accumulation by 14% at day 14, and Alp transcription levels by 16%, and matrix mineralization by 17% at day 21 compared with remission RA-sera. In HPDCs, active RA-sera inhibited metabolic activity by 8%, SOX9 transcription levels by 14%, and cartilage matrix accumulation by 7% at day 7 compared with remission RA-sera. In conclusion, sera from patients with active RA negatively affect differentiation of osteochondrogenic precursors, and as a consequence may contribute to delayed fracture healing in these patients.

  13. The Synergistic Effects of Matrix Stiffness and Composition on the Response of Chondroprogenitor Cells in a 3D Precondensation Microenvironment.

    PubMed

    Carrion, Bita; Souzanchi, Mohammad F; Wang, Victor T; Tiruchinapally, Gopinath; Shikanov, Ariella; Putnam, Andrew J; Coleman, Rhima M

    2016-05-01

    Improve functional quality of cartilage tissue engineered from stem cells requires a better understanding of the functional evolution of native cartilage tissue. Therefore, a biosynthetic hydrogel was developed containing RGD, hyaluronic acid and/or type-I collagen conjugated to poly(ethylene glycol) acrylate to recapitulate the precondensation microenvironment of the developing limb. Conjugation of any combination of the three ligands did not alter the shear moduli or diffusion properties of the PEG hydrogels; thus, the influence of ligand composition on chondrogenesis could be investigated in the context of varying matrix stiffness. Gene expression of ligand receptors (CD44 and the b1-integrin) as well as markers of condensation (cell clustering and N-cadherin gene expression) and chondrogenesis (Col2a1 gene expression and sGAG production) by chondroprogenitor cells in this system were modulated by both matrix stiffness and ligand composition, with the highest gene expression occurring in softer hydrogels containing all three ligands. Cell proliferation in these 3D matrices for 7 d prior to chondrogenic induction increased the rate of sGAG production in a stiffness-dependent manner. This biosynthetic hydrogel supports the features of early limb-bud condensation and chondrogenesis and is a novel platform in which the influence of the matrix physicochemical properties on these processes can be elucidated.

  14. TiO2 nanotube stimulate chondrogenic differentiation of limb mesenchymal cells by modulating focal activity

    PubMed Central

    Kim, Dongkyun; Choi, Bohm; Song, Jinsoo; Kim, Sunhyo; Oh, Seunghan; Jin, Eun-Heui; Kang, Shin-Sung

    2011-01-01

    Vertically aligned, laterally spaced nanoscale titanium nanotubes were grown on a titanium surface by anodization, and the growth of chondroprogenitors on the resulting surfaces was investigated. Surfaces bearing nanotubes of 70 to 100 nm in diameter were found to trigger the morphological transition to a cortical actin pattern and rounded cell shape (both indicative of chondrocytic differentiation), as well as the up-regulation of type II collagen and integrin β4 protein expression through the down-regulation of Erk activity. Inhibition of Erk signaling reduced stress fiber formation and induced the transition to the cortical actin pattern in cells cultured on 30-nm-diameter nanotubes, which maintained their fibroblastoid morphologies in the absence of Erk inhibition. Collectively, these results indicate that a titanium-based nanotube surface can support chondrocytic functions among chondroprogenitors, and may therefore be useful for future cartilaginous applications. PMID:21677506

  15. Lysyl oxidase-like-2 (LOXL2) is a major isoform in chondrocytes and is critically required for differentiation.

    PubMed

    Iftikhar, Mussadiq; Hurtado, Paola; Bais, Manish V; Wigner, Nate; Stephens, Danielle N; Gerstenfeld, Louis C; Trackman, Philip C

    2011-01-14

    The lysyl oxidase family is made up of five members: lysyl oxidase (LOX) and lysyl oxidase-like 1-4 (LOXL1-LOXL4). All members share conserved C-terminal catalytic domains that provide for lysyl oxidase or lysyl oxidase-like enzyme activity; and more divergent propeptide regions. LOX family enzyme activities catalyze the final enzymatic conversion required for the formation of normal biosynthetic collagen and elastin cross-links. The importance of lysyl oxidase enzyme activity to normal bone development has long been appreciated, but regulation and roles for specific LOX isoforms in bone formation in vivo is largely unexplored. Fracture healing recapitulates aspects of endochondral bone development. The present study first investigated the expression of all LOX isoforms in fracture healing. A remarkable coincidence of LOXL2 expression with the chondrogenic phase of fracture healing was found, prompting more detailed analyses of LOXL2 expression in normal growth plates, and LOXL2 expression and function in developing ATDC5 chondrogenic cells. Data show that LOXL2 is expressed by pre-hypertrophic and hypertrophic chondrocytes in vivo, and that LOXL2 expression is regulated in vitro as a function of chondrocyte differentiation. Moreover, LOXL2 knockdown studies in vitro show that LOXL2 expression is required for ATDC5 chondrocyte cell line differentiation through regulation of SNAIL and SOX9, important transcription factors that control chondrocyte differentiation. Taken together, data provide evidence that LOXL2, like LOX, is a multifunctional protein. LOXL2 promotes chondrocyte differentiation by mechanisms that are likely to include roles as both a regulator and an effector of chondrocyte differentiation.

  16. Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

    PubMed

    Imamura, Katsuyuki; Maeda, Shingo; Kawamura, Ichiro; Matsuyama, Kanehiro; Shinohara, Naohiro; Yahiro, Yuhei; Nagano, Satoshi; Setoguchi, Takao; Yokouchi, Masahiro; Ishidou, Yasuhiro; Komiya, Setsuro

    2014-04-01

    Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

  17. The immunohistochemical localization of notch receptors and ligands in human articular cartilage, chondroprogenitor culture and ultrastructural characteristics of these progenitor cells.

    PubMed

    Ustunel, Ismail; Ozenci, Alpay Merter; Sahin, Zeliha; Ozbey, Ozlem; Acar, Nuray; Tanriover, Gamze; Celik-Ozenci, Ciler; Demir, Ramazan

    2008-01-01

    The presence of progenitor/stem cells in human articular cartilage remains controversial. Therefore, we attempted to isolate and culture progenitor/stem cells and to investigate their phenotypic characteristics. Biopsies were obtained (with consent) from patients undergoing arthroscopic surgery. Full depth explants were fixed and cryosectioned or enzymatically digested and the resulting cells cultured and plated on fibronectin-coated dishes. Chondrocytes were cultured until colonies of >32 cells were present. Colonies were trypsinized and expanded in monolayer for pellet culture. Immunolocalization of Notch and its ligands were detected in vivo and in vitro using immunocytochemistry. In vitro studies investigated differences in immunolocalization of Notch and its associated ligands in colony-forming cells and small clusters of non-colony-forming cells. The ultrastructure of the chondroprogenitors was examined by scanning and transmission electron microscopy. Results revealed that the immunolocalization of Notch-1 and its ligand Delta were concentrated in regions closest to the articular surface. Notch-1 was also densely localized in the deeper zone of articular cartilage. Notch-2 immunolabeling was densely localized in all zones of articular cartilage. Jagged-1 was concentrated in the deeper regions of articular cartilage. Notch-1, Delta and Jagged-1 were more abundant in colony-forming cells than non-colony-forming chondrocytes in vitro. Notch-3, Notch-4 and Jagged-2 were absent from all regions of the articular cartilage tissues and cultured cartilage cells in vitro. Ultrastructurally, chondrocytes cultured in monolayer dedifferentiated to fibroblast-like cells with cell surface processes of varying lengths, pellet cultured cells varied in morphology, as flattened and rounded. In conclusion, we propose that adult human articular cartilage may contain cells having progenitor cell features. PMID:18272209

  18. ECM stiffness primes the TGFβ pathway to promote chondrocyte differentiation

    PubMed Central

    Allen, Jessica L.; Cooke, Margaret E.; Alliston, Tamara

    2012-01-01

    Cells encounter physical cues such as extracellular matrix (ECM) stiffness in a microenvironment replete with biochemical cues. However, the mechanisms by which cells integrate physical and biochemical cues to guide cellular decision making are not well defined. Here we investigate mechanisms by which chondrocytes generate an integrated response to ECM stiffness and transforming growth factor β (TGFβ), a potent agonist of chondrocyte differentiation. Primary murine chondrocytes and ATDC5 cells grown on 0.5-MPa substrates deposit more proteoglycan and express more Sox9, Col2α1, and aggrecan mRNA relative to cells exposed to substrates of any other stiffness. The chondroinductive effect of this discrete stiffness, which falls within the range reported for articular cartilage, requires the stiffness-sensitive induction of TGFβ1. Smad3 phosphorylation, nuclear localization, and transcriptional activity are specifically increased in cells grown on 0.5-MPa substrates. ECM stiffness also primes cells for a synergistic response, such that the combination of ECM stiffness and exogenous TGFβ induces chondrocyte gene expression more robustly than either cue alone through a p38 mitogen-activated protein kinase–dependent mechanism. In this way, the ECM stiffness primes the TGFβ pathway to efficiently promote chondrocyte differentiation. This work reveals novel mechanisms by which cells integrate physical and biochemical cues to exert a coordinated response to their unique cellular microenvironment. PMID:22833566

  19. The Increase in O-Linked N-Acetylglucosamine Protein Modification Stimulates Chondrogenic Differentiation Both in Vitro and in Vivo*

    PubMed Central

    Andrés-Bergós, Jessica; Tardio, Lidia; Larranaga-Vera, Ane; Gómez, Rodolfo; Herrero-Beaumont, Gabriel; Largo, Raquel

    2012-01-01

    Insulin is an inducer of chondrocyte hypertrophy and growth plate chondrogenesis, although the specific molecular mechanisms behind these effects are mostly unknown. Our aim was to investigate whether insulin-induced chondrocyte hypertrophy occurs through a modification in the amount of O-linked N-acetylglucosamine (O-GlcNAc)-modified proteins and in the expression of the key enzymes of this pathway, O-GlcNAc transferase and O-GlcNAcase (OGA). We also studied if O-GlcNAc accumulation per se, induced by an OGA inhibitor, was able to induce pre-hypertrophic chondrocyte differentiation both in vitro and in vivo. Insulin-induced differentiation of ATDC5 pre-chondrocytes occurred alongside a gradual increase in the accumulation of O-GlcNac-modified proteins (O-GlcNAcylated proteins), as well as an increase in the expression of O-GlcNAc transferase and OGA. In the absence of insulin, O-GlcNAc accumulation induced by thiamet-G, a specific OGA inhibitor, was able to increase the gene expression of differentiation markers, as well as the activity of MMP-2 and -9. Thiamet-G also activated pERK, p-JNK, and p-p38 and the O-GlcNAcylation of Akt. Thiamet-G administration to C57/bl mice induced a significant expansion in the growth plate height and in the hypertrophic zone height. Therefore, our results show that O-GlcNAc glycosylation has chondromodulating activity. PMID:22859309

  20. Quantification of type II procollagen splice forms using Alternative Transcript-qPCR (AT-qPCR)

    PubMed Central

    McAlinden, Audrey; Shim, Kyu-Hwan; Wirthlin, Louisa; Ravindran, Soumya; Hering, Thomas M.

    2012-01-01

    During skeletal development, the onset of chondrogenic differentiation is marked by expression of the α1(II) procollagen Col2a1) gene. Exon 2 of Col2a1 codes for a cysteine-rich von Willebrand factor C-like domain. Chondroprogenitors express the exon 2-containing IIA and IID splice forms by utilizing adjacent 5′ splice sites separated by 3 base pairs. There is a shift to expression of the shorter, exon 2-lacking IIB splice form with further differentiation. Alternative splicing analysis of Col2a1 splice forms has often relied upon semi-quantitative PCR, using a single set of PCR primers to amplify multiple splice forms. We show that this widely used method is inaccurate due to mismatched amplification efficiency of different-sized PCR products. We have developed the TaqMan®-based AT-qPCR (Alternative Transcript-qPCR) assay to more accurately quantify alternatively spliced mRNA, and demonstrate the measurement of Col2a1 splice form expression in differentiating ATDC5 cells in vitro and in wild type mouse embryonic and postnatal cartilage in vivo. The AT-qPCR assay is based on the use of a multiple amplicon standard (MAS) plasmid, containing a chemically synthesized cluster of splice site-spanning PCR amplicons, to quantify alternative splice forms by standard curve-based qPCR. The MAS plasmid designed for Col2a1 also contained an 18S rRNA amplicon for sample normalization, and an amplicon corresponding to a region spanning exon 52-53 to measure total Col2a1 mRNA. In mouse E12.5 to P70 cartilage, we observed the expected switch between the IIA and IIB splice forms; no IID or IIC splice products were observed. However, in the ATDC5 cultures, predominant expression of the IIA and IID splice forms was found at all times in culture. Additionally, we observed that the sum of the IIA, IIB and IID splice forms comprises only a small fraction of Col2a1 transcripts containing the constitutive exon 52-53 junction. We conclude from our results that the majority of ATDC5

  1. Oxygen tension affects lubricin expression in chondrocytes.

    PubMed

    Hatta, Taku; Kishimoto, Koshi N; Okuno, Hiroshi; Itoi, Eiji

    2014-10-01

    We assessed the effects of oxygen tension on lubricin expression in bovine chondrocytes and cartilage explants and a role for hypoxia-inducible transcription factor (HIF)-1α in regulating lubricin expression was investigated using a murine chondroprogenitor cell line, ATDC5, and bovine chondrocytes isolated from superficial and middle/deep zones of femoral cartilage. ATDC5 cells and bovine chondrocytes were cultured in micromass under different oxygen tensions (21%, 5%, and 1%). ATDC5 cells and middle/deep zone chondrocytes that initially had low lubricin expression levels were also cultured with or without transforming growth factor (TGF)-β1. Quantitative reverse transcription (RT)-PCR was used to determine lubricin and chondrogenic marker gene mRNA levels and immunohistochemistry was used to assess lubricin protein expression. Explant cartilage plugs cultured under different oxygen tensions were also subjected to immunohistological analysis for lubricin. HIF-1α gene silencing was achieved by electroporatic transfer into ATDC5 cells. A low oxygen tension reduced lubricin gene expression levels in bovine superficial chondrocytes, TGF-β1-treated middle/deep zone chondrocytes, and TGF-β1-treated ATDC5 cells. Lubricin expression in explant cartilage was also suppressed under hypoxia. HIF-1α gene silencing in ATDC5 cells attenuated the lubricin expression response to the oxygen tension. These results corroborate with previous studies that the oxygen tension regulates lubricin gene expression and suggest that HIF-1α plays an important role in this regulation. The normal distribution of lubricin in articular cartilage may be due to the hypoxic oxygen environment of cartilage as it is an avascular tissue. An oxygen tension gradient may be a key factor for engineering cartilage tissue with a layered morphology.

  2. Small molecule-directed specification of sclerotome-like chondroprogenitors and induction of a somitic chondrogenesis program from embryonic stem cells.

    PubMed

    Zhao, Jiangang; Li, Songhui; Trilok, Suprita; Tanaka, Makoto; Jokubaitis-Jameson, Vanta; Wang, Bei; Niwa, Hitoshi; Nakayama, Naoki

    2014-10-01

    Pluripotent embryonic stem cells (ESCs) generate rostral paraxial mesoderm-like progeny in 5-6 days of differentiation induced by Wnt3a and Noggin (Nog). We report that canonical Wnt signaling introduced either by forced expression of activated β-catenin, or the small-molecule inhibitor of Gsk3, CHIR99021, satisfied the need for Wnt3a signaling, and that the small-molecule inhibitor of BMP type I receptors, LDN193189, was able to replace Nog. Mesodermal progeny generated using such small molecules were chondrogenic in vitro, and expressed trunk paraxial mesoderm markers such as Tcf15 and Meox1, and somite markers such as Uncx, but failed to express sclerotome markers such as Pax1. Induction of the osteochondrogenically committed sclerotome from somite requires sonic hedgehog and Nog. Consistently, Pax1 and Bapx1 expression was induced when the isolated paraxial mesodermal progeny were treated with SAG1 (a hedgehog receptor agonist) and LDN193189, then Sox9 expression was induced, leading to cartilaginous nodules and particles in the presence of BMP, indicative of chondrogenesis via sclerotome specification. By contrast, treatment with TGFβ also supported chondrogenesis and stimulated Sox9 expression, but failed to induce the expression of Pax1 and Bapx1. On ectopic transplantation to immunocompromised mice, the cartilage particles developed under either condition became similarly mineralized and formed pieces of bone with marrow. Thus, the use of small molecules led to the effective generation from ESCs of paraxial mesodermal progeny, and to their further differentiation in vitro through sclerotome specification into growth plate-like chondrocytes, a mechanism resembling in vivo somitic chondrogenesis that is not recapitulated with TGFβ. PMID:25294938

  3. Delta-like 1/Fetal Antigen-1 (Dlk1/FA1) Is a Novel Regulator of Chondrogenic Cell Differentiation via Inhibition of the Akt Kinase-dependent Pathway*

    PubMed Central

    Chen, Li; Qanie, Diyako; Jafari, Abbas; Taipaleenmaki, Hanna; Jensen, Charlotte H.; Säämänen, Anna-Marja; Sanz, Maria Luisa Nueda; Laborda, Jorge; Abdallah, Basem M.; Kassem, Moustapha

    2011-01-01

    Delta-like 1 (Dlk1, also known as fetal antigen-1, FA1) is a member of Notch/Delta family that inhibits adipocyte and osteoblast differentiation; however, its role in chondrogenesis is still not clear. Thus, we overexpressed Dlk1/FA1 in mouse embryonic ATDC5 cells and tested its effects on chondrogenic differentiation. Dlk1/FA1 inhibited insulin-induced chondrogenic differentiation as evidenced by reduction of cartilage nodule formation and gene expression of aggrecan, collagen Type II and X. Similar effects were obtained either by using Dlk1/FA1-conditioned medium or by addition of a purified, secreted, form of Dlk1 (FA1) directly to the induction medium. The inhibitory effects of Dlk1/FA1 were dose-dependent and occurred irrespective of the chondrogenic differentiation stage: proliferation, differentiation, maturation, or hypertrophic conversion. Overexpression or addition of the Dlk1/FA1 protein to the medium strongly inhibited the activation of Akt, but not the ERK1/2, or p38 MAPK pathways, and the inhibition of Akt by Dlk1/FA1 was mediated through PI3K activation. Interestingly, inhibition of fibronectin expression by siRNA rescued the Dlk1/FA1-mediated inhibition of Akt, suggesting interaction of Dlk1/FA1 and fibronectin in chondrogenic cells. Our results identify Dlk1/FA1 as a novel regulator of chondrogenesis and suggest Dlk1/FA1 acts as an inhibitor of the PI3K/Akt pathways that leads to its inhibitory effects on chondrogenesis. PMID:21724852

  4. Meclozine Facilitates Proliferation and Differentiation of Chondrocytes by Attenuating Abnormally Activated FGFR3 Signaling in Achondroplasia

    PubMed Central

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  5. Meclozine facilitates proliferation and differentiation of chondrocytes by attenuating abnormally activated FGFR3 signaling in achondroplasia.

    PubMed

    Matsushita, Masaki; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Kaneko, Hiroshi; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2013-01-01

    Achondroplasia (ACH) is one of the most common skeletal dysplasias with short stature caused by gain-of-function mutations in FGFR3 encoding the fibroblast growth factor receptor 3. We used the drug repositioning strategy to identify an FDA-approved drug that suppresses abnormally activated FGFR3 signaling in ACH. We found that meclozine, an anti-histamine drug that has long been used for motion sickness, facilitates chondrocyte proliferation and mitigates loss of extracellular matrix in FGF2-treated rat chondrosarcoma (RCS) cells. Meclozine also ameliorated abnormally suppressed proliferation of human chondrosarcoma (HCS-2/8) cells that were infected with lentivirus expressing constitutively active mutants of FGFR3-K650E causing thanatophoric dysplasia, FGFR3-K650M causing SADDAN, and FGFR3-G380R causing ACH. Similarly, meclozine alleviated abnormally suppressed differentiation of ATDC5 chondrogenic cells expressing FGFR3-K650E and -G380R in micromass culture. We also confirmed that meclozine alleviates FGF2-mediated longitudinal growth inhibition of embryonic tibia in bone explant culture. Interestingly, meclozine enhanced growth of embryonic tibia in explant culture even in the absence of FGF2 treatment. Analyses of intracellular FGFR3 signaling disclosed that meclozine downregulates phosphorylation of ERK but not of MEK in FGF2-treated RCS cells. Similarly, meclozine enhanced proliferation of RCS cells expressing constitutively active mutants of MEK and RAF but not of ERK, which suggests that meclozine downregulates the FGFR3 signaling by possibly attenuating ERK phosphorylation. We used the C-natriuretic peptide (CNP) as a potent inhibitor of the FGFR3 signaling throughout our experiments, and found that meclozine was as efficient as CNP in attenuating the abnormal FGFR3 signaling. We propose that meclozine is a potential therapeutic agent for treating ACH and other FGFR3-related skeletal dysplasias. PMID:24324705

  6. Expression of Two Novel Alternatively Spliced COL2A1 Isoforms During Chondrocyte Differentiation

    PubMed Central

    McAlinden, Audrey; Johnstone, Brian; Kollar, John; Kazmi, Najam; Hering, Thomas M.

    2008-01-01

    Alternative splicing of the type II procollagen gene (COL2A1) is developmentally-regulated during chondrogenesis. Type IIA procollagen (+ exon 2) is synthesized by chondroprogenitor cells while type IIB procollagen (- exon 2) is synthesized by differentiated chondrocytes. Here, we report expression of two additional alternatively spliced COL2A1 isoforms during chondrocyte differentiation of bone marrow derived mesenchymal stem cells (MSCs). One isoform, named IIC, contains only the first 34 nucleotides of exon 2 by use of an alternative 5’ splice site, resulting in a premature termination codon and possible nonsense-mediated decay of IIC mRNA. Low levels of the IIC isoform were detected by RT-PCR and Southern analysis of COL2A1 cDNA amplified from differentiating rabbit and human MSCs. A second novel transcript, named IID, arises by use of another 5’ alternative splice site in intron 2. The IID isoform contains exon 2 plus 3 nucleotides, resulting in the insertion of an additional amino acid. The IID isoform was co-expressed with the IIA isoform during chondrogenesis, and was approximately one-third as abundant. Deletion of the IIC alternative 5’ splice site from a COL2A1 mini-gene construct resulted in a significant increase in the IIA:IIB ratio. A mutant mini-gene that inhibited production of the IID isoform, however, had differential effects on the production of the IIA and IIB isoforms: this was apparently related to the differentiation status of the cell type used. These data suggest that COL2A1 mRNA abundance and other aspects of chondrocyte differentiation may be regulated by the use of these previously undetermined alternative splice sites. PMID:18023161

  7. Chondrogenesis, chondrocyte differentiation, and articular cartilage metabolism in health and osteoarthritis.

    PubMed

    Goldring, Mary B

    2012-08-01

    Chondrogenesis occurs as a result of mesenchymal cell condensation and chondroprogenitor cell differentiation. Following chondrogenesis, the chondrocytes remain as resting cells to form the articular cartilage or undergo proliferation, terminal differentiation to chondrocyte hypertrophy, and apoptosis in a process termed endochondral ossification, whereby the hypertrophic cartilage is replaced by bone. Human adult articular cartilage is a complex tissue of matrix proteins that varies from superficial to deep layers and from loaded to unloaded zones. A major challenge to efforts to repair cartilage by stem cell-based and other tissue-engineering strategies is the inability of the resident chondrocytes to lay down a new matrix with the same properties as it had when it was formed during development. Thus, understanding and comparing the mechanisms of cartilage remodeling during development, osteoarthritis (OA), and aging may lead to more effective strategies for preventing cartilage damage and promoting repair. The pivotal proteinase that marks OA progression is matrix metalloproteinase 13 (MMP-13), the major type II collagen-degrading collagenase, which is regulated by both stress and inflammatory signals. We and other investigators have found that there are common mediators of these processes in human OA cartilage. We also observe temporal and spatial expression of these mediators in early through late stages of OA in mouse models and are analyzing the consequences of knockout or transgenic overexpression of critical genes. Since the chondrocytes in adult human cartilage are normally quiescent and maintain the matrix in a low turnover state, understanding how they undergo phenotypic modulation and promote matrix destruction and abnormal repair in OA may to lead to identification of critical targets for therapy to block cartilage damage and promote effective cartilage repair. PMID:22859926

  8. MEPE is a novel regulator of growth plate cartilage mineralization

    PubMed Central

    Staines, K.A.; Mackenzie, N.C.W.; Clarkin, C.E.; Zelenchuk, L.; Rowe, P.S.; MacRae, V.E.; Farquharson, C.

    2012-01-01

    Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. Although the growth plates of MEPE-overexpressing mice display severe morphological disruption, the expression and function of MEPE in growth plate matrix mineralization remains largely undefined. Here we show MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide, to be localised to the hypertrophic zone of the growth plate. We also demonstrate that the phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. Interestingly, we show that the addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. For a more physiologically relevant model, we utilized the metatarsal organ culture model. We show the pASARM peptide to inhibit mineralization at two stages of development, as shown by histological and μCT analysis. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. Taken together these results show MEPE to be an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide. PMID:22766095

  9. MEPE is a novel regulator of growth plate cartilage mineralization.

    PubMed

    Staines, K A; Mackenzie, N C W; Clarkin, C E; Zelenchuk, L; Rowe, P S; MacRae, V E; Farquharson, C

    2012-09-01

    Matrix extracellular phosphoglycoprotein (MEPE) belongs to the SIBLING protein family which play key roles in biomineralization. Although the growth plates of MEPE-overexpressing mice display severe morphological disruption, the expression and function of MEPE in growth plate matrix mineralization remains largely undefined. Here we show MEPE and its cleavage product, the acidic serine aspartate-rich MEPE-associated motif (ASARM) peptide, to be localised to the hypertrophic zone of the growth plate. We also demonstrate that the phosphorylated (p)ASARM peptide inhibits ATDC5 chondrocyte matrix mineralization. Stable MEPE-overexpressing ATDC5 cells also had significantly reduced matrix mineralization in comparison to the control cells. Interestingly, we show that the addition of the non-phosphorylated (np)ASARM peptide promoted mineralization in the ATDC5 cells. The peptides and the overexpression of MEPE did not affect the differentiation of the ATDC5 cells. For a more physiologically relevant model, we utilized the metatarsal organ culture model. We show the pASARM peptide to inhibit mineralization at two stages of development, as shown by histological and μCT analysis. Like in the ATDC5 cells, the peptides did not affect the differentiation of the metatarsals indicating that the effects seen on mineralization are direct, as is additionally confirmed by no change in alkaline phosphatase activity or mRNA expression. In the metatarsal organ cultures, the pASARM peptide also reduced endothelial cell markers and vascular endothelial growth factor mRNA expression. Taken together these results show MEPE to be an important regulator of growth plate chondrocyte matrix mineralization through its cleavage to an ASARM peptide.

  10. Differentiated Staffing.

    ERIC Educational Resources Information Center

    Geisinger, Robert W.; And Others

    This report describes school operation changes in scheduling, curriculum, decisionmaking powers, and individualization of instruction that are concurrent with the adoption of differentiated staffing. The author defines differentiated staffing, explains where and at what levels it has been utilized, provides descriptions of results achieved, gives…

  11. Differential games.

    NASA Technical Reports Server (NTRS)

    Varaiya, P. P.

    1972-01-01

    General discussion of the theory of differential games with two players and zero sum. Games starting at a fixed initial state and ending at a fixed final time are analyzed. Strategies for the games are defined. The existence of saddle values and saddle points is considered. A stochastic version of a differential game is used to examine the synthesis problem.

  12. DIFFERENTIAL ANALYZER

    DOEpatents

    Sorensen, E.G.; Gordon, C.M.

    1959-02-10

    Improvements in analog eomputing machines of the class capable of evaluating differential equations, commonly termed differential analyzers, are described. In general form, the analyzer embodies a plurality of basic computer mechanisms for performing integration, multiplication, and addition, and means for directing the result of any one operation to another computer mechanism performing a further operation. In the device, numerical quantities are represented by the rotation of shafts, or the electrical equivalent of shafts.

  13. Sexual differentiation.

    PubMed

    Sinisi, A A; Pasquali, D; Notaro, A; Bellastella, A

    2003-01-01

    In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for differentiation of the internal and external genitalia during fetal life, and for the development of secondary sex characteristics at puberty. Antimullerian hormone (AMH) secreted by Sertoli cells inhibits the development of female internal genitalia (tube, uterus, upper part of vagina); testosterone secreted by Leydig cells induces stabilization of wolffian ducts and development of internal male genitalia. Differentiation of external male genitalia requires the transformation of testosterone to dihydrotestosterone by 5alpha reductase type 2 expressed in genital skin and urogenital sinus. The effects of androgens occur in presence of functional androgen receptor (AR) protein. Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity. PMID:12834017

  14. Bacterial differentiation.

    PubMed

    Shapiro, L; Agabian-Keshishian, N; Bendis, I

    1971-09-01

    The foregoing studies are intended to define a differentiation process and to permit genetic access to the mechanisms that control this process. In order to elucidate the basic mechanisms whereby a cell dictates its own defined morphogenic changes, we have found it helpful to study an organism that can be manipulated both biochemically and genetically. We have attempted to develop the studies initiated by Poindexter,Stove and Stanier, and Schmidt and Stanier (16, 17, 20) with the Caulobacter genus so that these bacteria can serve as a model system for prokaryotic differentiation. The Caulobacter life cycle, defined in synchronously growing cultures, includes a sequential series of morphological changes that occur at specific times in the cycle and at specific locations in the cell. Six distinct cellular characteristics, which are peculiar to these bacteria, have been defined and include (i) the synthesis of a polar organelle which may be membranous (21-23), (ii) a satellite DNA in the stalked cell (26), (iii) pili to which RNA bacteriophage specifically adsorb (16, 33), (iv) a single polar flagellum(17), (v) a lipopolysaccharide phage receptor site (27), and (vi) new cell wall material at the flagellated pole of the cell giving rise to a stalk (19, 20). Cell division, essential for the viability of the organism, is dependent on the irreversible differentiation of a flagellated swarmer cell to a mature stalked cell. The specific features of the Caulobacter system which make it a system of choice for studies of the control of sequential events resulting in cellular differentiation can be summarized as follows. 1) Cell populations can be synchronized, and homogeneous populations at each stage in the differentiation cycle can thus be obtained. 2) A specific technique has been developed whereby the progress of the differentiation cycle can be accurately measured by adsorption of labeled RNA phage or penetration of labeled phage DNA into specific cell forms. This

  15. Tranilast stimulates endochondral ossification by upregulating SOX9 and RUNX2 promoters.

    PubMed

    Hasegawa, Sachi; Kitoh, Hiroshi; Ohkawara, Bisei; Mishima, Kenichi; Matsushita, Masaki; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2016-02-01

    Endochondral ossification is an essential process for reparative phase of fracture healing, which starts with the differentiation of mesenchymal cells into chondrocytes followed by substitution of bone tissue. It is strictly controlled by the expression of crucial transcriptional factors: SOX9 in the early phase and RUNX2 in the late phase. Screening of FDA-approved compounds revealed that an anti-allergic drug, tranilast, that has been used for more than 30 years in clinical practice, enhanced the SOX9 promoter in chondrogenic cells and the RUNX2 promoter in osteoblastic cells. We observed that tranilast increased mRNA expression of both Sox9 and Runx2 in differentiating ATDC5 chondrogenic progenitor cells. Tranilast upregulated mRNA expression of chondrogenic marker genes (Col2a1, Acan, Col10a1, and Mmp13) in differentiating ATDC5 cells. Moreover, tranilast upregulated mRNA expression of essential signaling molecules involved in endochondral ossification (Pthrp, Ihh, and Axin2). In the later phase of differentiation of ATDC5 cells, tranilast increased synthesis of matrix proteoglycans, induced the alkaline phosphatase activity, and tended to accelerate mineralization. Tranilast is a potential agent that accelerates fracture repair by promoting the regulatory steps of endochondral ossification. PMID:26777999

  16. Differential gearing

    SciTech Connect

    Tamiya, S.

    1986-07-29

    A differential for motor vehicles is described and the like comprising, an input drive shaft, a pair of coaxially spaced drive gears simultaneously driven by the input shaft in a same direction at a same speed of rotation about a common axis of rotation, a driven gear driven peripherally by the pair of drive gears for transmission of power from the input drive shaft, two coaxial opposed bevel sun gears having an axis of rotation concentric with an axis of rotation of the driven gear, two planetary gears disposed between the sun gears for differential driving thereof during turns of the vehicle to the right and to the left of each meshing with the sun gears for driving the suns gears. Each planetary gear has a separate axis of rotation carried by the driven gear disposed therein radially and symmetrically relative to the axis of rotation of the sun gears, and each sun gear having a respective power output shaft connected thereto for rotation therewith.

  17. Differentiated Instruction. Fastback.

    ERIC Educational Resources Information Center

    Smutny, Joan Franklin

    This fastback presents the essentials for understanding how to differentiate instruction to meet the learning needs of all students in today's classrooms. It focuses on: "The Need for Differentiated Instruction" (determining learning needs, deciding what to differentiate, and principles of differentiated instruction); "Strategies for…

  18. Automatic differentiation bibliography

    SciTech Connect

    Corliss, G.F.

    1992-07-01

    This is a bibliography of work related to automatic differentiation. Automatic differentiation is a technique for the fast, accurate propagation of derivative values using the chain rule. It is neither symbolic nor numeric. Automatic differentiation is a fundamental tool for scientific computation, with applications in optimization, nonlinear equations, nonlinear least squares approximation, stiff ordinary differential equation, partial differential equations, continuation methods, and sensitivity analysis. This report is an updated version of the bibliography which originally appeared in Automatic Differentiation of Algorithms: Theory, Implementation, and Application.

  19. Fast Differential Adder

    NASA Technical Reports Server (NTRS)

    Arditti, Mort A.; Silva, Rosemary

    1993-01-01

    Differential adding circuit (or, equivalently, subtracting circuit) faster and consumes less power because it contains only one differential amplifier. Suitable for use in high-frequency-switching, high power-regulating circuit.

  20. Using Differentials to Differentiate Trigonometric and Exponential Functions

    ERIC Educational Resources Information Center

    Dray, Tevian

    2013-01-01

    Starting from geometric definitions, we show how differentials can be used to differentiate trigonometric and exponential functions without limits, numerical estimates, solutions of differential equations, or integration.

  1. Mechanical fatigue performance of PCL-chondroprogenitor constructs after cell culture under bioreactor mechanical stimulus.

    PubMed

    Panadero, Juan Alberto; Sencadas, Vitor; Silva, Sonia C M; Ribeiro, Clarisse; Correia, Vitor; Gama, Francisco M; Gomez Ribelles, José Luis; Lanceros-Mendez, Senentxu

    2016-02-01

    In tissue engineering of cartilage, polymeric scaffolds are implanted in the damaged tissue and subjected to repeated compression loading cycles. The possibility of failure due to mechanical fatigue has not been properly addressed in these scaffolds. Nevertheless, the macroporous scaffold is susceptible to failure after repeated loading-unloading cycles. This is related to inherent discontinuities in the material due to the micropore structure of the macro-pore walls that act as stress concentration points. In this work, chondrogenic precursor cells have been seeded in poly-ε-caprolactone (PCL) scaffolds with fibrin and some were submitted to free swelling culture and others to cyclic loading in a bioreactor. After cell culture, all the samples were analyzed for fatigue behavior under repeated loading-unloading cycles. Moreover, some components of the extracellular matrix (ECM) were identified. No differences were observed between samples undergoing free swelling or bioreactor loading conditions, neither respect to matrix components nor to mechanical performance to fatigue. The ECM did not achieve the desired preponderance of collagen type II over collagen type I which is considered the main characteristic of hyaline cartilage ECM. However, prediction in PCL with ECM constructs was possible up to 600 cycles, an enhanced performance when compared to previous works. PCL after cell culture presents an improved fatigue resistance, despite the fact that the measured elastic modulus at the first cycle was similar to PCL with poly(vinyl alcohol) samples. This finding suggests that fatigue analysis in tissue engineering constructs can provide additional information missed with traditional mechanical measurements.

  2. Depolarizing differential Mueller matrices.

    PubMed

    Ortega-Quijano, Noé; Arce-Diego, José Luis

    2011-07-01

    The evolution of a polarized beam can be described by the differential formulation of Mueller calculus. The nondepolarizing differential Mueller matrices are well known. However, they only account for 7 out of the 16 independent parameters that are necessary to model a general anisotropic depolarizing medium. In this work we present the nine differential Mueller matrices for general depolarizing media, highlighting the physical implications of each of them. Group theory is applied to establish the relationship between the differential matrix and the set of transformation generators in the Minkowski space, of which Lorentz generators constitute a particular subgroup. PMID:21725434

  3. Mueller matrix differential decomposition.

    PubMed

    Ortega-Quijano, Noé; Arce-Diego, José Luis

    2011-05-15

    We present a Mueller matrix decomposition based on the differential formulation of the Mueller calculus. The differential Mueller matrix is obtained from the macroscopic matrix through an eigenanalysis. It is subsequently resolved into the complete set of 16 differential matrices that correspond to the basic types of optical behavior for depolarizing anisotropic media. The method is successfully applied to the polarimetric analysis of several samples. The differential parameters enable one to perform an exhaustive characterization of anisotropy and depolarization. This decomposition is particularly appropriate for studying media in which several polarization effects take place simultaneously. PMID:21593943

  4. Matrix differentiation formulas

    NASA Technical Reports Server (NTRS)

    Usikov, D. A.; Tkhabisimov, D. K.

    1983-01-01

    A compact differentiation technique (without using indexes) is developed for scalar functions that depend on complex matrix arguments which are combined by operations of complex conjugation, transposition, addition, multiplication, matrix inversion and taking the direct product. The differentiation apparatus is developed in order to simplify the solution of extremum problems of scalar functions of matrix arguments.

  5. Differential Person Functioning.

    ERIC Educational Resources Information Center

    Johanson, George; Alsmadi, Abdalla

    In many testing situations, differential item functioning (DIF) is a potentially serious problem. It occurs when a test item appears to be easier for one group of examinees than another even after controlling for overall skill level. Differential person functioning (DPF) can occur when "items" can be considered raters and the persons are the…

  6. Differentiated Staffing and Practice

    ERIC Educational Resources Information Center

    Christie, Kathy

    2005-01-01

    The development of the positions of nurse practitioner and physician assistant is a good example of differentiating staffing and practice to meet individual needs in an effective and cost-efficient way. This type of differentiation has been confined to the healthcare industry, principally to health maintenance organizations, but perhaps those in…

  7. Automatic Differentiation Package

    SciTech Connect

    Gay, David M.; Phipps, Eric; Bratlett, Roscoe

    2007-03-01

    Sacado is an automatic differentiation package for C++ codes using operator overloading and C++ templating. Sacado provide forward, reverse, and Taylor polynomial automatic differentiation classes and utilities for incorporating these classes into C++ codes. Users can compute derivatives of computations arising in engineering and scientific applications, including nonlinear equation solving, time integration, sensitivity analysis, stability analysis, optimization and uncertainity quantification.

  8. Differential Grading Standards Revisited.

    ERIC Educational Resources Information Center

    Strenta, A. Christopher; Elliott, Rogers

    1987-01-01

    Differential grading standards were examined in a sample of 1,029 Dartmouth College graduates. Fields of study that attracted students (as majors) who scored higher on the Scholastic Aptitude Test (SAT) employed stricter grading standards. These differential standards attenuated the substantial correlation between SAT scores and grades.…

  9. Differentiating Instruction: Why Bother?

    ERIC Educational Resources Information Center

    Tomlinson, Carol Ann

    2005-01-01

    In her more than 30 years of teaching, the author has practiced differentiation in her own classroom at all educational levels. Although she is well familiar with the vocabulary, research and reasoning behind it, the most compelling answer she can give for why differentiation matters in the middle grades comes from her personal experience as an…

  10. Lifting the Differentiation Embargo.

    PubMed

    Latif, Anne-Louise; Holyoake, Tessa L

    2016-09-22

    Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. PMID:27662083

  11. Nonlinear differential equations

    SciTech Connect

    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.

  12. Musculoskeletal mnemonics: differentiating features.

    PubMed

    Currie, Jonathan W; Davis, Kirkland W; Lafita, Vaishali S; Blankenbaker, Donna G; De Smet, Arthur A; Rosas, Humberto; Lee, Kenneth S

    2011-01-01

    Mnemonics are often used in musculoskeletal radiology to help radiologists remember long differential diagnoses. However, unless the specific appearance of each entity on a differential is also recalled, mnemonics become useless. This article presents 8 mnemonics with their corresponding differential diagnoses and distinguishing features. Bubbly lucent lesions of bone are recalled with the FEGNOMASHIC mnemonic, but when only lucent lesions of the diaphysis are included, a more appropriate mnemonic is FEMALE. The lucent lesions of bone differentials often can be narrowed based on specific characteristics of the lesion but radiographic findings elsewhere and clinical information often help. Osseous metastases may present as lucent or sclerotic lesions; when sclerotic, the differential is best remembered with the mnemonic 5 "BEES" Like Pollen. The mnemonic for Wormian bones is PORKCHOPS. The Wormian bones in most of these entities are indistinguishable, so one must rely on radiographic findings outside the skull for diagnosis. By contrast, differentiating causes of acro-osteolysis is often possible with findings seen only on the hand radiographs; the mnemonic for acro-osteolysis is RADSHIP. In skeletally immature patients with frayed metaphyses, the mnemonic is CHARMS. Although the appearance of the fraying is seldom diagnostic, findings in the adjacent portions of the long bones may be characteristic. FETISH is the mnemonic used to remember the entities for the differential diagnosis of vertebra plana. Age of the patient, clinical history, and findings in the adjacent spine often help to provide the specific diagnosis. Nearly all the entities on the differential diagnosis for distal clavicle erosion (mnemonic: SHIRT Pocket) are included in other differentials in this article. PMID:21266270

  13. Pseudo Perceptual Differentiation

    ERIC Educational Resources Information Center

    Silverman, Julian; King, Catherine

    1970-01-01

    Two studies employing rod-and-frame test (RFT) and a size-estimation measure of "extensiveness of scanning reported. Results indicated perceptual differentiation interpretation of RFT performance erroneous for certain kinds of Ss. (Author)

  14. Palmitate differentially regulates the polarization of differentiating and differentiated macrophages.

    PubMed

    Xiu, Fangming; Diao, Li; Qi, Peter; Catapano, Michael; Jeschke, Marc G

    2016-01-01

    The tissue accumulation of M1 macrophages in patients with metabolic diseases such as obesity and type 2 diabetes mellitus has been well-documented. Interestingly, it is an accumulation of M2 macrophages that is observed in the adipose, liver and lung tissues, as well as in the circulation, of patients who have had major traumas such as a burn injury or sepsis; however, the trigger for the M2 polarization observed in these patients has not yet been identified. In the current study, we explored the effects of chronic palmitate and high glucose treatment on macrophage differentiation and function in murine bone-marrow-derived macrophages. We found that chronic treatment with palmitate decreased phagocytosis and HLA-DR expression in addition to inhibiting the production of pro-inflammatory cytokines. Chronic palmitate treatment of bone marrows also led to M2 polarization, which correlated with the activation of the peroxisome proliferator-activated receptor-γ signalling pathway. Furthermore, we found that chronic palmitate treatment increased the expression of multiple endoplasmic reticulum (ER) stress markers, including binding immunoglobulin protein. Preconditioning with the universal ER stress inhibitor 4-phenylbutyrate attenuated ER stress signalling and neutralized the effect of palmitate, inducing a pro-inflammatory phenotype. We confirmed these results in differentiating human macrophages, showing an anti-inflammatory response to chronic palmitate exposure. Though alone it did not promote M2 polarization, hyperglycaemia exacerbated the effects of palmitate. These findings suggest that the dominant accumulation of M2 in adipose tissue and liver in patients with critical illness may be a result of hyperlipidaemia and hyperglycaemia, both components of the hypermetabolism observed in critically ill patients.

  15. Solving Ordinary Differential Equations

    NASA Technical Reports Server (NTRS)

    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.

  16. Repair of Cartilage Defects in Arthritic Tissue with Differentiated Human Embryonic Stem Cells

    PubMed Central

    Olee, Tsaiwei; Grogan, Shawn P.; Lotz, Martin K.; Colwell, Clifford W.

    2014-01-01

    Chondrocytes have been generated in vitro from a range of progenitor cell types and by a number of strategies. However, achieving reconstitution of actual physiologically relevant, appropriately-laminated cartilage in situ that would be applicable to conditions, such as arthritis and cartilage degeneration remains elusive. This lack of success is multifactorial and includes limited cell source, decreased proliferation rate of mature chondrocytes, lack of maintenance of phenotype, reduced matrix synthesis, and poor integration with host tissue. We report an efficient approach for deriving mesenchymal chondroprogenitor cells from human embryonic stem cells. These cells generated tissue containing cartilage-specific matrix proteins that integrated in situ in a partial-thickness defect in ex vivo articular cartilage harvested from human arthritic joints. Given that stem cells provide a virtually inexhaustible supply of starting material and that our technique is easily scalable, cartilaginous tissue primed and grafted in this manner could be suitable for clinical translation. PMID:24028447

  17. [Differential diagnosis of hoarseness].

    PubMed

    Voigt-Zimmermann, S; Lampe, K; Arens, C

    2014-04-01

    Hoarseness can be the leading symptom of dysphonia. In combination with impaired vocal performance and subjective voice-related discomfort, it can represent an individually different handicap for patients and lead to limited participation in social and professional life. Since the reasons for dysphonia may be not only functional but also organic with a potentially poor prognosis, hoarseness must be clarified using differential diagnosis. In addition to the knowledge of possible diseases, pathogenesis, and treatment options for dysphonia, the differential diagnostic approach requires profound knowledge of the various diagnostic methods, and of the interpretation of the results in particular. The etiology of dysphonia is very diverse and rarely monocausal. Therefore, a team-based and interdisciplinary differential diagnostic approach is recommended.

  18. Cross-differential amplifier

    NASA Technical Reports Server (NTRS)

    Hajimiri, Seyed-Ali (Inventor); Kee, Scott D. (Inventor); Aoki, Ichiro (Inventor)

    2008-01-01

    A cross-differential amplifier is provided. The cross-differential amplifier includes an inductor connected to a direct current power source at a first terminal. A first and second switch, such as transistors, are connected to the inductor at a second terminal. A first and second amplifier are connected at their supply terminals to the first and second switch. The first and second switches are operated to commutate the inductor between the amplifiers so as to provide an amplified signal while limiting the ripple voltage on the inductor and thus limiting the maximum voltage imposed across the amplifiers and switches.

  19. Cross-differential amplifier

    NASA Technical Reports Server (NTRS)

    Hajimiri, Seyed-Ali (Inventor); Kee, Scott D. (Inventor); Aoki, Ichiro (Inventor)

    2011-01-01

    A cross-differential amplifier is provided. The cross-differential amplifier includes an inductor connected to a direct current power source at a first terminal. A first and second switch, such as transistors, are connected to the inductor at a second terminal. A first and second amplifier are connected at their supply terminals to the first and second switch. The first and second switches are operated to commutate the inductor between the amplifiers so as to provide an amplified signal while limiting the ripple voltage on the inductor and thus limiting the maximum voltage imposed across the amplifiers and switches.

  20. Cross-differential amplifier

    NASA Technical Reports Server (NTRS)

    Hajimiri, Seyed-Ali (Inventor); Kee, Scott D. (Inventor); Aoki, Ichiro (Inventor)

    2010-01-01

    A cross-differential amplifier is provided. The cross-differential amplifier includes an inductor connected to a direct current power source at a first terminal. A first and second switch, such as transistors, are connected to the inductor at a second terminal. A first and second amplifier are connected at their supply terminals to the first and second switch. The first and second switches are operated to commutate the inductor between the amplifiers so as to provide an amplified signal while limiting the ripple voltage on the inductor and thus limiting the maximum voltage imposed across the amplifiers and switches.

  1. Cross-differential amplifier

    NASA Technical Reports Server (NTRS)

    Hajimiri, Seyed-Ali (Inventor); Kee, Scott D. (Inventor); Aoki, Ichiro (Inventor)

    2013-01-01

    A cross-differential amplifier is provided. The cross-differential amplifier includes an inductor connected to a direct current power source at a first terminal. A first and second switch, such as transistors, are connected to the inductor at a second terminal. A first and second amplifier are connected at their supply terminals to the first and second switch. The first and second switches are operated to commutate the inductor between the amplifiers so as to provide an amplified signal while limiting the ripple voltage on the inductor and thus limiting the maximum voltage imposed across the amplifiers and switches.

  2. Stochastic differential equations

    SciTech Connect

    Sobczyk, K. )

    1990-01-01

    This book provides a unified treatment of both regular (or random) and Ito stochastic differential equations. It focuses on solution methods, including some developed only recently. Applications are discussed, in particular an insight is given into both the mathematical structure, and the most efficient solution methods (analytical as well as numerical). Starting from basic notions and results of the theory of stochastic processes and stochastic calculus (including Ito's stochastic integral), many principal mathematical problems and results related to stochastic differential equations are expounded here for the first time. Applications treated include those relating to road vehicles, earthquake excitations and offshore structures.

  3. Differential comparator cirucit

    DOEpatents

    Hickling, Ronald M.

    1996-01-01

    A differential comparator circuit for an Analog-to-Digital Converter (ADC) or other application includes a plurality of differential comparators and a plurality of offset voltage generators. Each comparator includes first and second differentially connected transistor pairs having equal and opposite voltage offsets. First and second offset control transistors are connected in series with the transistor pairs respectively. The offset voltage generators generate offset voltages corresponding to reference voltages which are compared with a differential input voltage by the comparators. Each offset voltage is applied to the offset control transistors of at least one comparator to set the overall voltage offset of the comparator to a value corresponding to the respective reference voltage. The number of offset voltage generators required in an ADC application can be reduced by a factor of approximately two by applying the offset voltage from each offset voltage generator to two comparators with opposite logical sense such that positive and negative offset voltages are produced by each offset voltage generator.

  4. Differentiation. Research Brief

    ERIC Educational Resources Information Center

    Walker, Karen

    2005-01-01

    The idea of differentiation was initiated by educators of and researchers for students who were classified as gifted and talented. Subsequently, this concept has become part of the general belief system that educators must meet and address the needs of every child, regardless of ability levels. Researchers have found that most teachers state that…

  5. Differentiation: Transparent or Opaque?

    ERIC Educational Resources Information Center

    Schroeder-Davis, Stephen

    2012-01-01

    In the author's experience, when concerns about camouflaging differentiation occur, they tend to center around issues related to fear of stigmatizing students who are working ahead of (or behind) their age-peers. These fears often manifest in specific concerns about grouping arrangements, as well as the issues of fairness, grading, and confusion…

  6. Differentiated Science Inquiry

    ERIC Educational Resources Information Center

    Llewellyn, Douglas

    2010-01-01

    Given that each child learns differently, it makes sense that one type of science instruction does not fit all. Best-selling author Douglas Llewellyn gives teachers standards-based strategies for differentiating inquiry-based science instruction to more effectively meet the needs of all students. This book takes the concept of inquiry-based…

  7. [Cluster headache differential diagnosis].

    PubMed

    Guégan-Massardier, Evelyne; Laubier, Cécile

    2015-11-01

    Cluster headache is characterized by disabling stereotyped headache. Early diagnosis allows appropriate treatment, unfortunately diagnostic errors are frequent. The main differential diagnoses are other primary or essential headaches. Migraine, more frequent and whose diagnosis is carried by excess, trigeminal neuralgia or other trigemino-autonomic cephalgia. Vascular or tumoral underlying condition can mimic cluster headache, neck and brain imaging is recommended, ideally MRI.

  8. Environmental Attitudes Semantic Differential.

    ERIC Educational Resources Information Center

    Mehne, Paul R.; Goulard, Cary J.

    This booklet is an evaluation instrument which utilizes semantic differential data to assess environmental attitudes. Twelve concepts are included: regulated access to beaches, urban planning, dune vegetation, wetlands, future cities, reclaiming wetlands for building development, city parks, commercial development of beaches, existing cities,…

  9. Molecular Typing and Differentiation

    EPA Science Inventory

    In this chapter, general background and bench protocols are provided for a number of molecular typing techniques in common use today. Methods for the molecular typing and differentiation of microorganisms began to be widely adopted following the development of the polymerase chai...

  10. Do Differential Equations Swing?

    ERIC Educational Resources Information Center

    Maruszewski, Richard F., Jr.

    2006-01-01

    One of the units of in a standard differential equations course is a discussion of the oscillatory motion of a spring and the associated material on forcing functions and resonance. During the presentation on practical resonance, the instructor may tell students that it is similar to when they take their siblings to the playground and help them on…

  11. Modelling by Differential Equations

    ERIC Educational Resources Information Center

    Chaachoua, Hamid; Saglam, Ayse

    2006-01-01

    This paper aims to show the close relation between physics and mathematics taking into account especially the theory of differential equations. By analysing the problems posed by scientists in the seventeenth century, we note that physics is very important for the emergence of this theory. Taking into account this analysis, we show the…

  12. Analyticity without Differentiability

    ERIC Educational Resources Information Center

    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…

  13. Issues in Differential Response

    ERIC Educational Resources Information Center

    Hughes, Ronald C.; Rycus, Judith S.; Saunders-Adams, Stacey M.; Hughes, Laura K.; Hughes, Kelli N.

    2013-01-01

    Differential response (DR), also referred to as alternative response (AR), family assessment response (FAR), or multiple track response, was developed to incorporate family-centered, strengths-based practices into child protective services (CPS), primarily by diverting lower risk families into an assessment track rather than requiring the…

  14. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

    PubMed

    Glass, Donald A; Bialek, Peter; Ahn, Jong Deok; Starbuck, Michael; Patel, Millan S; Clevers, Hans; Taketo, Mark M; Long, Fanxin; McMahon, Andrew P; Lang, Richard A; Karsenty, Gerard

    2005-05-01

    Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast differentiation and suggest that it may regulate bone formation in differentiated osteoblasts. Here, we study later events and find that stabilization of beta-catenin in differentiated osteoblasts results in high bone mass, while its deletion from differentiated osteoblasts leads to osteopenia. Surprisingly, histological analysis showed that these mutations primarily affect bone resorption rather than bone formation. Cellular and molecular studies showed that beta-catenin together with TCF proteins regulates osteoblast expression of Osteoprotegerin, a major inhibitor of osteoclast differentiation. These findings demonstrate that beta-catenin, and presumably Wnt signaling, promote the ability of differentiated osteoblasts to inhibit osteoclast differentiation; thus, they broaden our knowledge of the functions Wnt proteins have at various stages of skeletogenesis. PMID:15866165

  15. Fertility differentials in Nigeria.

    PubMed

    Ogum, G E

    1980-01-01

    A review of the numerous fertility studies carried out in Nigeria during the last 3 decades. Evidence of differences in fertility among subgroups of the population is gleaned from these studies, as very few have addressed this issue specifically. Results still need to be evaluated. The only strong indication of possible geographic fertility differentials remains Van de Walle's analysis of age data from the census of 1952-53. 2 studies among populations of southwestern Nigeria yielded conflicting results with regard to urban-rural differentials, 1 finding lower fertility among urban residents while the other found no differences. Similarly, 2 studies with regard to religious differences yielded somewhat conflicting results, 1 showing Moslems and traditional worshippers having higher fertility than Christians, the other showing Moslems with lower fertility than traditional believers. There is some consensus among researchers that education has some depressing effect on fertility.

  16. Differential auger spectrometry

    DOEpatents

    Strongin, Myron; Varma, Matesh Narayan; Anne, Joshi

    1976-06-22

    Differential Auger spectroscopy method for increasing the sensitivity of micro-Auger spectroanalysis of the surfaces of dilute alloys, by alternately periodically switching an electron beam back and forth between an impurity free reference sample and a test sample containing a trace impurity. The Auger electrons from the samples produce representative Auger spectrum signals which cancel to produce an Auger test sample signal corresponding to the amount of the impurity in the test samples.

  17. Differential homogeneous immunosensor device

    DOEpatents

    Malmros, Mark K.; Gulbinski, III, Julian

    1990-04-10

    There is provided a novel method of testing for the presence of an analyte in a fluid suspected of containing the same. In this method, in the presence of the analyte, a substance capable of modifying certain characteristics of the substrate is bound to the substrate and the change in these qualities is measured. While the method may be modified for carrying out quantitative differential analyses, it eliminates the need for washing analyte from the substrate which is characteristic of prior art methods.

  18. SIMULTANEOUS DIFFERENTIAL EQUATION COMPUTER

    DOEpatents

    Collier, D.M.; Meeks, L.A.; Palmer, J.P.

    1960-05-10

    A description is given for an electronic simulator for a system of simultaneous differential equations, including nonlinear equations. As a specific example, a homogeneous nuclear reactor system including a reactor fluid, heat exchanger, and a steam boiler may be simulated, with the nonlinearity resulting from a consideration of temperature effects taken into account. The simulator includes three operational amplifiers, a multiplier, appropriate potential sources, and interconnecting R-C networks.

  19. Multistate differential transmission

    SciTech Connect

    Whalen, B.

    1987-09-01

    A multistate transmission is described having an input shaft and an output shaft comprising: a. planetary gear train means having a ring gear, planetary gears with planetary gear carrier, and a sun gear, the planetary gear train means connected to the output shaft; b. first bypass means connecting the input shaft to the planetary gear train means; c. differential transmission means for receiving its input from the input shaft and having means to adjust the torque and speed output infinitely variable over its range of operation for each state of the transmission; d. power return means for receiving the output of the differential transmission means; e. means including clutch operated speed reversing means for interconnecting the sun gear in the planetary gear train means with the power return means; f. the power return means including a first gear to receive the output of the differential transmission means; g. first multispeed transmission means connecting the means for supporting the carrier shaft to the first bypass means.

  20. Is Titan Partially Differentiated?

    NASA Astrophysics Data System (ADS)

    Mitri, G.; Pappalardo, R. T.; Stevenson, D. J.

    2009-12-01

    The recent measurement of the gravity coefficients from the Radio Doppler data of the Cassini spacecraft has improved our knowledge of the interior structure of Titan (Rappaport et al. 2008 AGU, P21A-1343). The measured gravity field of Titan is dominated by near hydrostatic quadrupole components. We have used the measured gravitational coefficients, thermal models and the hydrostatic equilibrium theory to derive Titan's interior structure. The axial moment of inertia gives us an indication of the degree of the interior differentiation. The inferred axial moment of inertia, calculated using the quadrupole gravitational coefficients and the Radau-Darwin approximation, indicates that Titan is partially differentiated. If Titan is partially differentiated then the interior must avoid melting of the ice during its evolution. This suggests a relatively late formation of Titan to avoid the presence of short-lived radioisotopes (Al-26). This also suggests the onset of convection after accretion to efficiently remove the heat from the interior. The outer layer is likely composed mainly of water in solid phase. Thermal modeling indicates that water could be present also in liquid phase forming a subsurface ocean between an outer ice I shell and a high pressure ice layer. Acknowledgments: This work was conducted at the Jet Propulsion Laboratory, California Institute of Technology, under contract with the National Aeronautics and Space Administration.

  1. Temperature differential detection device

    DOEpatents

    Girling, P.M.

    1986-04-22

    A temperature differential detection device for detecting the temperature differential between predetermined portions of a container wall is disclosed as comprising a Wheatstone bridge circuit for detecting resistance imbalance with a first circuit branch having a first elongated wire element mounted in thermal contact with a predetermined portion of the container wall, a second circuit branch having a second elongated wire element mounted in thermal contact with a second predetermined portion of a container wall with the wire elements having a predetermined temperature-resistant coefficient, an indicator interconnected between the first and second branches remote from the container wall for detecting and indicating resistance imbalance between the first and second wire elements, and connector leads for electrically connecting the wire elements to the remote indicator in order to maintain the respective resistance value relationship between the first and second wire elements. The indicator is calibrated to indicate the detected resistance imbalance in terms of a temperature differential between the first and second wall portions. 2 figs.

  2. Temperature differential detection device

    DOEpatents

    Girling, Peter M.

    1986-01-01

    A temperature differential detection device for detecting the temperature differential between predetermined portions of a container wall is disclosed as comprising a Wheatstone bridge circuit for detecting resistance imbalance with a first circuit branch having a first elongated wire element mounted in thermal contact with a predetermined portion of the container wall, a second circuit branch having a second elongated wire element mounted in thermal contact with a second predetermined portion of a container wall with the wire elements having a predetermined temperature-resistant coefficient, an indicator interconnected between the first and second branches remote from the container wall for detecting and indicating resistance imbalance between the first and second wire elements, and connector leads for electrically connecting the wire elements to the remote indicator in order to maintain the respective resistance value relationship between the first and second wire elements. The indicator is calibrated to indicate the detected resistance imbalance in terms of a temperature differential between the first and second wall portions.

  3. Differential transimpedance amplifier circuit for correlated differential amplification

    DOEpatents

    Gresham, Christopher A.; Denton, M. Bonner; Sperline, Roger P.

    2008-07-22

    A differential transimpedance amplifier circuit for correlated differential amplification. The amplifier circuit increase electronic signal-to-noise ratios in charge detection circuits designed for the detection of very small quantities of electrical charge and/or very weak electromagnetic waves. A differential, integrating capacitive transimpedance amplifier integrated circuit comprising capacitor feedback loops performs time-correlated subtraction of noise.

  4. Putting Differentials Back into Calculus

    ERIC Educational Resources Information Center

    Dray, Tevian; Manogue, Corrine A.

    2010-01-01

    We argue that the use of differentials in introductory calculus courses is useful and provides a unifying theme, leading to a coherent view of the calculus. Along the way, we meet several interpretations of differentials, some better than others.

  5. Differentiability in Several Variables Revisited

    ERIC Educational Resources Information Center

    Spindler, K.

    2007-01-01

    This paper introduces a concept of differentiability for functions in several variables which has a very natural definition and shares all the properties one expects of a notion of differentiability, but is shown to be weaker than the usual concept of differentiability defined as local linearizability. The exact connection between the two…

  6. Differential operator multiplication method for fractional differential equations

    NASA Astrophysics Data System (ADS)

    Tang, Shaoqiang; Ying, Yuping; Lian, Yanping; Lin, Stephen; Yang, Yibo; Wagner, Gregory J.; Liu, Wing Kam

    2016-11-01

    Fractional derivatives play a very important role in modeling physical phenomena involving long-range correlation effects. However, they raise challenges of computational cost and memory storage requirements when solved using current well developed numerical methods. In this paper, the differential operator multiplication method is proposed to address the issues by considering a reaction-advection-diffusion equation with a fractional derivative in time. The linear fractional differential equation is transformed into an integer order differential equation by the proposed method, which can fundamentally fix the aforementioned issues for select fractional differential equations. In such a transform, special attention should be paid to the initial conditions for the resulting differential equation of higher integer order. Through numerical experiments, we verify the proposed method for both fractional ordinary differential equations and partial differential equations.

  7. Differential operator multiplication method for fractional differential equations

    NASA Astrophysics Data System (ADS)

    Tang, Shaoqiang; Ying, Yuping; Lian, Yanping; Lin, Stephen; Yang, Yibo; Wagner, Gregory J.; Liu, Wing Kam

    2016-08-01

    Fractional derivatives play a very important role in modeling physical phenomena involving long-range correlation effects. However, they raise challenges of computational cost and memory storage requirements when solved using current well developed numerical methods. In this paper, the differential operator multiplication method is proposed to address the issues by considering a reaction-advection-diffusion equation with a fractional derivative in time. The linear fractional differential equation is transformed into an integer order differential equation by the proposed method, which can fundamentally fix the aforementioned issues for select fractional differential equations. In such a transform, special attention should be paid to the initial conditions for the resulting differential equation of higher integer order. Through numerical experiments, we verify the proposed method for both fractional ordinary differential equations and partial differential equations.

  8. Signalling pathway involved in nitric oxide synthase type II activation in chondrocytes: synergistic effect of leptin with interleukin-1

    PubMed Central

    Otero, Miguel; Lago, Rocío; Lago, Francisca; Reino, Juan Jesús Gomez; Gualillo, Oreste

    2005-01-01

    The objective of the present study was to investigate the effect of leptin, alone or in combination with IL-1, on nitric oxide synthase (NOS) type II activity in vitro in human primary chondrocytes, in the mouse chondrogenic ATDC5 cell line, and in mature and hypertrophic ATDC5 differentiated chondrocytes. For completeness, we also investigated the signalling pathway of the putative synergism between leptin and IL-1. For this purpose, nitric oxide production was evaluated using the Griess colorimetric reaction in culture medium of cells stimulated over 48 hours with leptin (800 nmol/l) and IL-1 (0.025 ng/ml), alone or combined. Specific pharmacological inhibitors of NOS type II (aminoguanidine [1 mmol/l]), janus kinase (JAK)2 (tyrphostin AG490 and Tkip), phosphatidylinositol 3-kinase (PI3K; wortmannin [1, 2.5, 5 and 10 μmol/l] and LY294002 [1, 2.5, 5 and 10 μmol/l]), mitogen-activated protein kinase kinase (MEK)1 (PD098059 [1, 5, 10, 20 and 30 μmol/l]) and p38 kinase (SB203580 [1, 5, 10, 20 and 30 μmol/l]) were added 1 hour before stimulation. Nitric oxide synthase type II mRNA expression in ATDC5 chondrocytes was investigated by real-time PCR and NOS II protein expression was analyzed by western blot. Our results indicate that stimulation of chondrocytes with IL-1 results in dose-dependent nitric oxide production. In contrast, leptin alone was unable to induce nitric oxide production or expression of NOS type II mRNA or its protein. However, co-stimulation with leptin and IL-1 resulted in a net increase in nitric oxide concentration over IL-1 challenge that was eliminated by pretreatment with the NOS II specific inhibitor aminoguanidine. Pretreatment with tyrphostin AG490 and Tkip (a SOCS-1 mimetic peptide that inhibits JAK2) blocked nitric oxide production induced by leptin/IL-1. Finally, wortmannin, LY294002, PD098059 and SB203580 significantly decreased nitric oxide production. These findings were confirmed in mature and hypertrophic ATDC5 chondrocytes, and

  9. Differentiating among penal states.

    PubMed

    Lacey, Nicola

    2010-12-01

    This review article assesses Loïc Wacquant's contribution to debates on penality, focusing on his most recent book, Punishing the Poor: The Neoliberal Government of Social Insecurity (Wacquant 2009), while setting its argument in the context of his earlier Prisons of Poverty (1999). In particular, it draws on both historical and comparative methods to question whether Wacquant's conception of 'the penal state' is adequately differentiated for the purposes of building the explanatory account he proposes; about whether 'neo-liberalism' has, materially, the global influence which he ascribes to it; and about whether, therefore, the process of penal Americanization which he asserts in his recent writings is credible. PMID:21138432

  10. Equivariant differential embeddings

    NASA Astrophysics Data System (ADS)

    Cross, Daniel J.; Gilmore, R.

    2010-09-01

    Takens [Dynamical Systems and Turbulence, Lecture Notes in Mathematics, edited by D. A. Rand and L. S. Young (Springer-Verlag, New York, 1981), Vol. 898, pp. 366-381] has shown that a dynamical system may be reconstructed from scalar data taken along some trajectory of the system. A reconstruction is considered successful if it produces a system diffeomorphic to the original. However, if the original dynamical system is symmetric, it is natural to search for reconstructions that preserve this symmetry. These generally do not exist. We demonstrate that a differential reconstruction of any nonlinear dynamical system preserves at most a twofold symmetry.

  11. Differentiating among penal states.

    PubMed

    Lacey, Nicola

    2010-12-01

    This review article assesses Loïc Wacquant's contribution to debates on penality, focusing on his most recent book, Punishing the Poor: The Neoliberal Government of Social Insecurity (Wacquant 2009), while setting its argument in the context of his earlier Prisons of Poverty (1999). In particular, it draws on both historical and comparative methods to question whether Wacquant's conception of 'the penal state' is adequately differentiated for the purposes of building the explanatory account he proposes; about whether 'neo-liberalism' has, materially, the global influence which he ascribes to it; and about whether, therefore, the process of penal Americanization which he asserts in his recent writings is credible.

  12. Differential homogeneous immunosensor device

    DOEpatents

    Malmros, M.K.; Gulbinski, J. III.

    1990-04-10

    There is provided a novel method of testing for the presence of an analyte in a fluid suspected of containing the same. In this method, in the presence of the analyte, a substance capable of modifying certain characteristics of the substrate is bound to the substrate and the change in these qualities is measured. While the method may be modified for carrying out quantitative differential analyses, it eliminates the need for washing the analyte from the substrate which is characteristic of prior art methods. 12 figs.

  13. DIFFERENTIAL FAULT SENSING CIRCUIT

    DOEpatents

    Roberts, J.H.

    1961-09-01

    A differential fault sensing circuit is designed for detecting arcing in high-voltage vacuum tubes arranged in parallel. A circuit is provided which senses differences in voltages appearing between corresponding elements likely to fault. Sensitivity of the circuit is adjusted to some level above which arcing will cause detectable differences in voltage. For particular corresponding elements, a group of pulse transformers are connected in parallel with diodes connected across the secondaries thereof so that only voltage excursions are transmitted to a thyratron which is biased to the sensitivity level mentioned.

  14. Differential diagnosis of hyponatraemia.

    PubMed

    Thompson, Chris; Berl, Tomas; Tejedor, Alberto; Johannsson, Gudmundur

    2012-03-01

    The appropriate management of hyponatraemia is reliant on the accurate identification of the underlying cause of the hyponatraemia. In the light of evidence which has shown that the use of a clinical algorithm appears to improve accuracy in the differential diagnosis of hyponatraemia, the European Hyponatraemia Network considered the use of two algorithms. One was developed from a nephrologist's view of hyponatraemia, while the other reflected the approach of an endocrinologist. Both of these algorithms concurred on the importance of assessing effective blood volume status and the measurement of urine sodium concentration in the diagnostic process. To demonstrate the importance of accurate diagnosis to the correct treatment of hyponatraemia, special consideration was given to hyponatraemia in neurosurgical patients. The differentiation between the syndrome of inappropriate antidiuretic hormone secretion (SIADH), acute adrenocorticotropic hormone (ACTH) deficiency, fluid overload and cerebral salt-wasting syndrome was discussed. In patients with SIADH, fluid restriction has been the mainstay of treatment despite the absence of an evidence base for its use. An approach to using fluid restriction to raise serum tonicity in patients with SIADH and to identify patients who are likely to be recalcitrant to fluid restriction was also suggested.

  15. Differential diagnosis of hyponatraemia.

    PubMed

    Thompson, Chris; Berl, Tomas; Tejedor, Alberto; Johannsson, Gudmundur

    2012-03-01

    The appropriate management of hyponatraemia is reliant on the accurate identification of the underlying cause of the hyponatraemia. In the light of evidence which has shown that the use of a clinical algorithm appears to improve accuracy in the differential diagnosis of hyponatraemia, the European Hyponatraemia Network considered the use of two algorithms. One was developed from a nephrologist's view of hyponatraemia, while the other reflected the approach of an endocrinologist. Both of these algorithms concurred on the importance of assessing effective blood volume status and the measurement of urine sodium concentration in the diagnostic process. To demonstrate the importance of accurate diagnosis to the correct treatment of hyponatraemia, special consideration was given to hyponatraemia in neurosurgical patients. The differentiation between the syndrome of inappropriate antidiuretic hormone secretion (SIADH), acute adrenocorticotropic hormone (ACTH) deficiency, fluid overload and cerebral salt-wasting syndrome was discussed. In patients with SIADH, fluid restriction has been the mainstay of treatment despite the absence of an evidence base for its use. An approach to using fluid restriction to raise serum tonicity in patients with SIADH and to identify patients who are likely to be recalcitrant to fluid restriction was also suggested. PMID:22469249

  16. Abnormalities of sex differentiation.

    PubMed

    Nawata, H; Takayanagi, R; Yanase, T; Ikuyama, S; Okabe, T

    1996-01-01

    Sex differentiation is determined by a cascade of events proceeding from chromosomal sex to the completion of sexual maturation at puberty. Many factors involved in this cascade have been identified. Here we focus on DAX-1, androgen receptor and cytochrome P450c17, and discuss their functions in sex differentiation. We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism using PCR amplification of genomic DNA and complete exonic sequencing, and established that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. Androgen insensitivity syndrome (AIS) is a good model to clarify the relationship between the structure and function of androgen receptor, the androgen receptor gene mutation and clinical phenotype. We analyzed 15 cases of AIS and demonstrate the structural and functional relationships of the androgen receptor. We have sequenced the CYP17 (P450c17) gene in DNA from several patients with 17 alpha-hydroxylase deficiency, reconstructed the mutations in a human P450c17 cDNA and expressed the mutant P450c17 in COSl cells to characterize the kinetic properties of 17 alpha-hydroxylase and 17,20-lyase activities. The molecular bases of cases clinically reported as 17 alpha-hydroxylase deficiency have turned out to be complete or partial combined deficiencies of 17 alpha-hydroxylase/17,20-lyase. PMID:8864743

  17. Ureter growth and differentiation.

    PubMed

    Bohnenpoll, Tobias; Kispert, Andreas

    2014-12-01

    The mammalian ureter is a slender tube that connects the renal pelvis with the bladder. It allows the unidirectional movement of urine by means of a peristaltically active smooth muscle layer that together with fibroelastic material ensheathes a water-impermeable multilayered urothelium. The ureteric urothelium as well as the outer mesenchymal coat arise from undifferentiated precursor tissues, the distal ureteric bud and its surrounding mesenchyme, respectively. Specification, growth and differentiation of these ureteric precursor tissues are tightly linked to each other, and are highly integrated with those of the adjacent rudiments of kidney and bladder. Here, we review the current knowledge on the cellular mechanisms as well as the molecular players that guide development of the tissue architecture of the ureter and its peristalsis. PMID:25087982

  18. Practical Differential Profiling

    SciTech Connect

    Schulz, M; De Supinski, B R

    2007-02-04

    Comparing performance profiles from two runs is an essential performance analysis step that users routinely perform. In this work we present eGprof, a tool that facilitates these comparisons through differential profiling inside gprof. We chose this approach, rather than designing a new tool, since gprof is one of the few performance analysis tools accepted and used by a large community of users. eGprof allows users to 'subtract' two performance profiles directly. It also includes callgraph visualization to highlight the differences in graphical form. Along with the design of this tool, we present several case studies that show how eGprof can be used to find and to study the differences of two application executions quickly and hence can aid the user in this most common step in performance analysis. We do this without requiring major changes on the side of the user, the most important factor in guaranteeing the adoption of our tool by code teams.

  19. DIFFERENTIAL PULSE HEIGHT DISCRIMINATOR

    DOEpatents

    Test, L.D.

    1958-11-11

    Pulse-height discriminators are described, specifically a differential pulse-height discriminator which is adapted to respond to pulses of a band of amplitudes, but to reject pulses of amplitudes greater or less than tbe preselected band. In general, the discriminator includes a vacuum tube having a plurality of grids adapted to cut off plate current in the tube upon the application of sufficient negative voltage. One grid is held below cutoff, while a positive pulse proportional to the amplltude of each pulse is applled to this grid. Another grid has a negative pulse proportional to the amplitude of each pulse simultaneously applied to it. With this arrangement the tube will only pass pulses which are of sufficlent amplitude to counter the cutoff bias but not of sufficlent amplitude to cutoff the tube.

  20. Differentiation as symbiosis.

    PubMed

    Chigira, M; Watanabe, H

    1994-07-01

    Preservation of the identity of DNA is the ultimate goal of multicellular organisms. An abnormal DNA sequence in cells within an individual means its parasitic nature in cell society as shown in tumors. Somatic gene arrangement and gene mutation in development may be considered as de novo formation of parasites. It is likely that the developmental process with genetic alterations means symbiosis between altered cells and germ line cells preserving genetic information without alterations, when somatic alteration of DNA sequence is a major mechanism of differentiation. According to the selfish gene theory of Dawkins, germ line cells permit symbiosis when somatic cell society derives clear profit for the replication of original DNA copies. PMID:7968715

  1. Population differentiation without speciation

    PubMed Central

    Magurran, A. E.

    1998-01-01

    Population differentiation is often viewed as an important step towards speciation, and part of the rationale for conserving variation at the intraspecific level is that the potential to generate more biological diversity should be retained. Yet, speciation is not an inevitable consequence of population divergence. This paper reviews recent work on the Trinidadian guppy, Poecilia reticulata, a species that is renowned for its capacity for population differentiation. Guppy populations evolve rapidly, within 101 to 102 generations, as a response to changes in selection exerted by predators. The rates of evolution involved can be up to seven orders of magnitude greater than those seen in the fossil record. Sexual selection, particuarly female choice, appears to reinforce the divergence that natural selection has generated. Perplexingly, however, there is no reproductive isolation (either prezygotic or postzygotic) between populations, even those that have been separated for at least 106 generations. Sexual conflict may be the key to explaining this absence of speciation. Male reproductive behaviour, particularly the high incidence of sneaky mating, may be instrumental in producing sufficient gene flow to prevent reproductive isolation. Sneaky mating has the potential to undermine female choice, and is known to be an important means of sperm transfer in wild populations. Sexual dimorphism, also a result of sexual conflict in guppies, may inhibit speciation in another way. Morphological differences between the sexes, that have arisen for reproductive reasons, mean that males and females are pre-adapted for different foraging niches. This, in turn, reduces the opportunity for the development of feeding polymorphisms, a mechanism that seems to have been important in the sympatric speciation of other fish species.

  2. Solving Differential Equations in R

    NASA Astrophysics Data System (ADS)

    Soetaert, Karline; Meysman, Filip; Petzoldt, Thomas

    2010-09-01

    The open-source software R has become one of the most widely used systems for statistical data analysis and for making graphs, but it is also well suited for other disciplines in scientific computing. One of the fields where considerable progress has been made is the solution of differential equations. Here we first give an overview of the types of differential equations that R can solve, and then demonstrate how to use R for solving a 2-Dimensional partial differential equation.

  3. Deferential Differentiation: What Types of Differentiation Do Students Want?

    ERIC Educational Resources Information Center

    Kanevsky, Lannie

    2011-01-01

    Deferential differentiation occurs when the curriculum modification process defers to students' preferred ways of learning rather than relying on teachers' judgments. The preferences of 416 students identified as gifted (grades 3-8) for features of differentiated curriculum recommended for gifted students were compared with those of 230 students…

  4. [Differentiated thyroid cancer -- 2009].

    PubMed

    Konrády, András

    2011-01-30

    Three years ago continental guidelines were published referring management and follow-up of low risk thyroid cancer patients. The aim of this paper is to summarize the changes and new directions in this field. High risk patients require another protocol. Neck ultrasound plays important role in differential diagnosis and in detecting recurrences. Some new ultrasound techniques are discussed, too. FDG-PET can help to solve the problem of patients having negative scan and increased thyroglobulin level. In recent years there was an expansion of our knowledge about the pathomechanism of thyroid cancer. It appears that genetic alterations frequently play a key role in carcinogenesis. There are molecular methods that allow the detection of these genetic events in thyroid fine needle aspirations samples providing important information for diagnosis, management and prognosis. Instead of diagnostic whole body scanning the posttherapeutic scan became preferable but in high risk cases the diagnostic whole body scintigrams serve useful data. Primary therapy of thyroid cancer is an adequate surgery: total thyreoidectomy and, if necessary, lymph node dissection or limited surgery in selected cases. Nowadays radioguided surgery can help to improve the results. Radioiodine therapy (e.g. rest ablation) proved to be a safe and effective method to complete surgery. It can prevent relapses and results in longer survival. Thyroid hormone withdrawal or recombinant human thyrotropin stimulation can increase thyrotropin level before radioiodine treatment. These two methods have similar success rate of rest ablation but irradiation burden of blood is lower in the case of exogenous stimulation which avoids hypothyroid state and preserves quality of life. Since tumor cells fail to maintain the ability to perform physiological functions they undergo dedifferentiation. Therefore, an important aim is to reactivate some function of differentiated cells, e.g. iodine uptake, production of

  5. Chondrocyte-intrinsic Smad3 represses Runx2-inducible MMP-13 expression to maintain articular cartilage and prevent osteoarthritis

    PubMed Central

    Chen, Carol G.; Thuillier, Daniel; Chin, Emily N.; Alliston, Tamara

    2012-01-01

    Objective To identify mechanisms by which Smad3 maintains articular cartilage and prevents osteoarthritis. Methods A combination of in vivo and in vitro approaches was used to test the hypothesis that Smad3 represses Runx2-inducible gene expression to prevent articular cartilage degeneration. Col2-Cre;Smad3fl/fl mice allowed study of the chondrocyte-intrinsic role of Smad3, independently of its role in the perichondrium or other tissues. Primary Smad3fl/fl articular chondrocytes and ATDC5 chondroprogenitors were employed to evaluate Smad3 and Runx2 regulation of matrix metalloproteinase-13 (MMP-13) mRNA and protein expression. Results Chondrocyte-specific reduction of Smad3 causes progressive articular cartilage degeneration due to imbalanced cartilage matrix synthesis and degradation. In addition to reduced collagen II mRNA expression, Col2-Cre;Smad3fl/fl articular cartilage is severely deficient in collagen II and aggrecan protein, due to excessive MMP-13-mediated proteolysis of these key cartilage matrix constituents. Normally, TGF-β signals through Smad3 to confer a rapid and dynamic repression of Runx2-inducible MMP-13 expression. However, in the absence of Smad3, TGF-β signals through p38 and Runx2 to induce MMP-13 expression. Conclusion This work elucidates a mechanism by which Smad3 mutations in humans and mice cause cartilage degeneration and osteoarthritis. Specifically, Smad3 maintains the balance between cartilage matrix synthesis and degradation by inducing collagen II expression and repressing Runx2-inducible MMP-13 expression. Selective activation of TGF-β signaling through Smad3, rather than p38, may help to restore the balance between matrix synthesis and proteolysis that is lost in osteoarthritis. PMID:22674505

  6. Making and Differentiating Planets

    NASA Astrophysics Data System (ADS)

    Taylor, G. J.

    2015-07-01

    The rocky planets formed by progressive aggregation of dust to make planetesimals which joined to make large objects called planetary embryos that finally accumulated into planets, one of which we live on. This chaotic process is complicated further by chemical changes with distance from the Sun, including differences in oxidation conditions and water concentration. Once the inner planets began to form, metallic iron sank to form cores, reacting with the rocky portions in the process. David C. Rubie (University of Bayreuth, Germany) and colleagues in Germany, France, and the United States put all this planetary action into an impressively thorough computer model of planet formation and differentiation. They show that the observed compositions of the Earth can be matched by simulations that include the Grand Tack (Jupiter and Saturn migrate inwards towards the Sun and then back out), and chemical gradients in the Solar System, with more reducing conditions near the Sun, more oxidizing farther from the Sun, and oxidizing and hydrated conditions even farther from the Sun. The study identifies other important variables, such as the extent to which metallic iron chemically equilibrated with the silicate making up the Earth's mantle, the pressure at which it happened, and the likelihood that Earth accreted heterogeneously.

  7. Differential Topic Models.

    PubMed

    Chen, Changyou; Buntine, Wray; Ding, Nan; Xie, Lexing; Du, Lan

    2015-02-01

    In applications we may want to compare different document collections: they could have shared content but also different and unique aspects in particular collections. This task has been called comparative text mining or cross-collection modeling. We present a differential topic model for this application that models both topic differences and similarities. For this we use hierarchical Bayesian nonparametric models. Moreover, we found it was important to properly model power-law phenomena in topic-word distributions and thus we used the full Pitman-Yor process rather than just a Dirichlet process. Furthermore, we propose the transformed Pitman-Yor process (TPYP) to incorporate prior knowledge such as vocabulary variations in different collections into the model. To deal with the non-conjugate issue between model prior and likelihood in the TPYP, we thus propose an efficient sampling algorithm using a data augmentation technique based on the multinomial theorem. Experimental results show the model discovers interesting aspects of different collections. We also show the proposed MCMC based algorithm achieves a dramatically reduced test perplexity compared to some existing topic models. Finally, we show our model outperforms the state-of-the-art for document classification/ideology prediction on a number of text collections. PMID:26353238

  8. Multiple symbol differential detection

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  9. Networked differential GPS system

    NASA Technical Reports Server (NTRS)

    Mueller, K. Tysen (Inventor); Loomis, Peter V. W. (Inventor); Kalafus, Rudolph M. (Inventor); Sheynblat, Leonid (Inventor)

    1994-01-01

    An embodiment of the present invention relates to a worldwide network of differential GPS reference stations (NDGPS) that continually track the entire GPS satellite constellation and provide interpolations of reference station corrections tailored for particular user locations between the reference stations Each reference station takes real-time ionospheric measurements with codeless cross-correlating dual-frequency carrier GPS receivers and computes real-time orbit ephemerides independently. An absolute pseudorange correction (PRC) is defined for each satellite as a function of a particular user's location. A map of the function is constructed, with iso-PRC contours. The network measures the PRCs at a few points, so-called reference stations and constructs an iso-PRC map for each satellite. Corrections are interpolated for each user's site on a subscription basis. The data bandwidths are kept to a minimum by transmitting information that cannot be obtained directly by the user and by updating information by classes and according to how quickly each class of data goes stale given the realities of the GPS system. Sub-decimeter-level kinematic accuracy over a given area is accomplished by establishing a mini-fiducial network.

  10. Differential Synthetic Aperture Ladar

    SciTech Connect

    Stappaerts, E A; Scharlemann, E

    2005-02-07

    We report a differential synthetic aperture ladar (DSAL) concept that relaxes platform and laser requirements compared to conventional SAL. Line-of-sight translation/vibration constraints are reduced by several orders of magnitude, while laser frequency stability is typically relaxed by an order of magnitude. The technique is most advantageous for shorter laser wavelengths, ultraviolet to mid-infrared. Analytical and modeling results, including the effect of speckle and atmospheric turbulence, are presented. Synthetic aperture ladars are of growing interest, and several theoretical and experimental papers have been published on the subject. Compared to RF synthetic aperture radar (SAR), platform/ladar motion and transmitter bandwidth constraints are especially demanding at optical wavelengths. For mid-IR and shorter wavelengths, deviations from a linear trajectory along the synthetic aperture length have to be submicron, or their magnitude must be measured to that precision for compensation. The laser coherence time has to be the synthetic aperture transit time, or transmitter phase has to be recorded and a correction applied on detection.

  11. Leadership for Differentiating Schools & Classrooms.

    ERIC Educational Resources Information Center

    Tomlinson, Carol Ann; Allan, Susan Demirsky

    Differentiation is simply a teacher attending to the learning needs of a particular student or small group of students, rather than teaching a class as though all individuals in it were basically alike. This book explores in 10 chapters how school leaders can develop responsive, personalized, and differentiated classrooms: (1) "Understanding…

  12. The Differentiated Classroom Observation Scale

    ERIC Educational Resources Information Center

    Cassady, Jerrell C.; Neumeister, Kristie L. Speirs; Adams, Cheryll M.; Cross, Tracy L.; Dixon, Felicia A.; Pierce, Rebecca L.

    2004-01-01

    This article presents a new classroom observation scale that was developed to examine the differential learning activities and experiences of gifted children educated in regular classroom settings. The Differentiated Classroom Observation Scale (DCOS) is presented in total, with clarification of the coding practices and strategies. Although the…

  13. Three Steps Lead to Differentiation

    ERIC Educational Resources Information Center

    Bowgren, Linda; Sever, Kathryn

    2010-01-01

    Much has been written about the value, need, and complexity of differentiating learning within every classroom based on student readiness, motivation and interest, apparent skills, learning preferences or styles, and identified cognitive needs. Teachers are encouraged to look at differentiation for students not as a formula for teaching, but…

  14. Au Contraire: Differentiation Requires HOPE

    ERIC Educational Resources Information Center

    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…

  15. Differentiation antigens in lymphohemopoietic tissues

    SciTech Connect

    Miyasaka, M.; Trnka, Z.

    1988-01-01

    This book contains 15 chapters. Some of the chapter titles are: In Situ Characterization of Human Lymphoid Cells Using Monoclonal Antibodies; Structural and Functional Aspects of HLA Clas II Genes; Cell-Surface Differentiation Antigens Expressed on Thymocytes and T Cells of the Mouse; and Differentiation Antigens on Lymphoid Cells of the Guinea Pig.

  16. The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

    PubMed Central

    Abella, Vanessa; Scotece, Morena; Conde, Javier; López, Verónica; Pirozzi, Claudio; Pino, Jesús; Gómez, Rodolfo; Lago, Francisca; González-Gay, Miguel Ángel; Gualillo, Oreste

    2016-01-01

    Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1β (IL1β) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1β or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1β- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1β or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNFα and IL1β stimulation. Our data showed that PGRN is able to significantly counteract the IL1β-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear anti-inflammatory function. PMID:26853108

  17. Job descriptions for differentiated nursing practice and differentiated pay.

    PubMed

    Forsey, L M; Cleland, V S; Miller, B

    1993-05-01

    Compensation of nurses in differentiated practice is based on distinctive job descriptions. The employer can then pay according to education, position, and actual performance level and seek to hire the staff mix that is most cost-effective for the institution. Both staff nursing and manager job descriptions are presented in this article. The authors discuss generic job descriptions that differentiate the practice of the staff nurse and the nurse unit manager according to the incumbent's educational level.

  18. Differential Doppler as a diagnostic

    SciTech Connect

    Dzieciuch, M.; Munk, W. )

    1994-10-01

    Differential Doppler compression and travel time of individual peaks in the arrival sequence (relative to an overall average) are measured for the 5500-km acoustic transmissions from a moving source at Heard Island to Christmas (Crab) Island. The differentials cannot be explained by simple adiabatic propagation models. A hybrid theory, coupling polar and temperate models at the Antarctic Front can account for some of the qualitative features. Differential Doppler could be a useful tool for identifying ray arrivals. 10 refs., 11 figs., 3 tabs.

  19. Differential form analysis using MACSYMA

    NASA Technical Reports Server (NTRS)

    Wahlquist, H. D.

    1977-01-01

    The MACSYMA file was written to perform these operations and discusses the improvements and additions which are needed to accomplish a complete and efficient implementation. Examples of differential form calculations are displayed.

  20. Differential Freshman Admission by Sex

    ERIC Educational Resources Information Center

    Suddick, David E.; McBee, M. Louise

    1974-01-01

    The authors report on a study whose purpose was to determine if, after adjusting for initial differences in high school averages and SAT scores via separate regression equations, differential admissions criterion by sex is justifiable. No justification is found. (RP)

  1. A Family of Differentiation Indices.

    ERIC Educational Resources Information Center

    Sachan, Ronaldo

    1984-01-01

    A general class of differentiation indices is introduced for profiles of scores. Their ordinal properties and an application to Holland's classification system are examined. Comparison with other suggested indices is performed both theoretically and empirically. (Author)

  2. Chiral anomalies and differential geometry

    SciTech Connect

    Zumino, B.

    1983-10-01

    Some properties of chiral anomalies are described from a geometric point of view. Topics include chiral anomalies and differential forms, transformation properties of the anomalies, identification and use of the anomalies, and normalization of the anomalies. 22 references. (WHK)

  3. Solving Differential Equations in R

    EPA Science Inventory

    Although R is still predominantly applied for statistical analysis and graphical representation, it is rapidly becoming more suitable for mathematical computing. One of the fields where considerable progress has been made recently is the solution of differential equations. Here w...

  4. Linear Back-Drive Differentials

    NASA Technical Reports Server (NTRS)

    Waydo, Peter

    2003-01-01

    Linear back-drive differentials have been proposed as alternatives to conventional gear differentials for applications in which there is only limited rotational motion (e.g., oscillation). The finite nature of the rotation makes it possible to optimize a linear back-drive differential in ways that would not be possible for gear differentials or other differentials that are required to be capable of unlimited rotation. As a result, relative to gear differentials, linear back-drive differentials could be more compact and less massive, could contain fewer complex parts, and could be less sensitive to variations in the viscosities of lubricants. Linear back-drive differentials would operate according to established principles of power ball screws and linear-motion drives, but would utilize these principles in an innovative way. One major characteristic of such mechanisms that would be exploited in linear back-drive differentials is the possibility of designing them to drive or back-drive with similar efficiency and energy input: in other words, such a mechanism can be designed so that a rotating screw can drive a nut linearly or the linear motion of the nut can cause the screw to rotate. A linear back-drive differential (see figure) would include two collinear shafts connected to two parts that are intended to engage in limited opposing rotations. The linear back-drive differential would also include a nut that would be free to translate along its axis but not to rotate. The inner surface of the nut would be right-hand threaded at one end and left-hand threaded at the opposite end to engage corresponding right- and left-handed threads on the shafts. A rotation and torque introduced into the system via one shaft would drive the nut in linear motion. The nut, in turn, would back-drive the other shaft, creating a reaction torque. Balls would reduce friction, making it possible for the shaft/nut coupling on each side to operate with 90 percent efficiency.

  5. MEK5 suppresses osteoblastic differentiation

    SciTech Connect

    Kaneshiro, Shoichi; Otsuki, Dai; Yoshida, Kiyoshi; Yoshikawa, Hideki; Higuchi, Chikahisa

    2015-07-31

    Extracellular signal-regulated kinase 5 (ERK5) is a member of the mitogen-activated protein kinase (MAPK) family and is activated by its upstream kinase, MAPK kinase 5 (MEK5), which is a member of the MEK family. Although the role of MEK5 has been investigated in several fields, little is known about its role in osteoblastic differentiation. In this study, we have demonstrated the role of MEK5 in osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells and bone marrow stromal ST2 cells. We found that treatment with BIX02189, an inhibitor of MEK5, increased alkaline phosphatase (ALP) activity and the gene expression of ALP, osteocalcin (OCN) and osterix, as well as it enhanced the calcification of the extracellular matrix. Moreover, osteoblastic cell proliferation decreased at a concentration of greater than 0.5 μM. In addition, knockdown of MEK5 using siRNA induced an increase in ALP activity and in the gene expression of ALP, OCN, and osterix. In contrast, overexpression of wild-type MEK5 decreased ALP activity and attenuated osteoblastic differentiation markers including ALP, OCN and osterix, but promoted cell proliferation. In summary, our results indicated that MEK5 suppressed the osteoblastic differentiation, but promoted osteoblastic cell proliferation. These results implied that MEK5 may play a pivotal role in cell signaling to modulate the differentiation and proliferation of osteoblasts. Thus, inhibition of MEK5 signaling in osteoblasts may be of potential use in the treatment of osteoporosis. - Highlights: • MEK5 inhibitor BIX02189 suppresses proliferation of osteoblasts. • MEK5 knockdown and MEK5 inhibitor promote differentiation of osteoblasts. • MEK5 overexpression inhibits differentiation of osteoblasts.

  6. Interpolated Differential Operator (IDO) scheme for solving partial differential equations

    NASA Astrophysics Data System (ADS)

    Aoki, Takayuki

    1997-05-01

    We present a numerical scheme applicable to a wide variety of partial differential equations (PDEs) in space and time. The scheme is based on a high accurate interpolation of the profile for the independent variables over a local area and repetitive differential operations regarding PDEs as differential operators. We demonstrate that the scheme is uniformly applicable to hyperbolic, ellipsoidal and parabolic equations. The equations are solved in terms of the primitive independent variables, so that the scheme has flexibility for various types of equations including source terms. We find out that the conservation holds accurate when a Hermite interpolation is used. For compressible fluid problems, the shock interface is found to be sharply described by adding an artificial viscosity term.

  7. Differentiation, ageing, and terminal differentiation: a semantic analysis.

    PubMed

    Reiner, J M

    1983-12-21

    The largely unsolved problems in the theoretical analysis of differentiation and ageing involve a substantial component of linguistic (semantic) difficulties. Some of these are simple traps of ambiguity, resulting from metaphorical or analogical employment of established terms--for example, "terminal differentiation" (loss of division potential in vitro) as a borrowing from "differentiation" as used by developmental biologists, or "commitment" by analogy with "determination". Some difficulties represent a failure to adopt (at least provisionally) an operational (empirical) view--for example, failure to ask what is the nature of the evidence for the view that a fertilized ovum is totipotential, or to scrutinize the evidence for the view that cells "terminally differentiated" in vitro in a conventional medium are in fact moribund under all conditions, or to examine more closely the view that the differentiated state and the cycling state are mutually exclusive. With respect to the problem of ageing, we review some of the critical experiments on "terminal differentiation" or "clonal senescence". We then proceed to consider some of the models that have been proposed, including a molecular model proposed by the author which appears to overcome some of the objections to other models. Some of the models exemplify the results of what are ultimately semantic vices. The problems with which these remarks began should indeed yield to the immense and novel resources of molecular biology. But the development of complete analyses demands not only good luck and delicate technique but also critical semantic clarity and severity. Given the best tools, we shall solve major theoretical problems only if we understand quite fully what problem it is that we are trying to solve--and the history of science illustrates that this is not as elementary a matter as it sounds.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Differential operator in seizure detection.

    PubMed

    Majumdar, Kaushik

    2012-01-01

    Differential operators can detect significant changes in signals. This has been utilized to enhance the contrast of the seizure signatures in depth EEG or ECoG. We have actually taken normalized exponential of absolute value of single or double derivative of epileptic ECoG. This in short we call differential filtering. Windowed variance operation has been performed to automatically detect seizure onset on differentially filtered signal. A novel method for determining the duration of seizure has also been proposed. Since all operations take only linear time, the whole method is extremely fast. Seven empirical parameters have been introduced whose patient specific thresholding brings down the rate of false detection to a bare minimum. Results of implementation of the methods on the ECoG data of four epileptic patients have been reported with an ROC curve analysis. High value of the area under the ROC curve indicates excellent detection performance.

  9. Local Algebras of Differential Operators

    NASA Astrophysics Data System (ADS)

    Church, P. T.; Timourian, J. G.

    2002-05-01

    There is an increasing literature devoted to the study of boundary value problems using singularity theory. The resulting differential operators are typically Fredholm with index 0, defined on infinite-dimensional spaces, and they have often led to folds, cusps, and even higher-order Morin singularities. In this paper we develop some of the local algebras of germs of such differential Fredholm operators, extending the theory of the finite-dimensional case. We apply this work to nonlinear elliptic boundary value problems: in particular, we make further progress on a question proposed and initially studied by Ruf [1999, J. Differential Equations 151, 111-133]. We also make comments on several problems raised by others.

  10. Physiological differentiation of viridans streptococci.

    PubMed Central

    Facklam, R R

    1977-01-01

    Twelve hundred and twenty-seven clinical isolates and eighty stock strains of viridans streptococci were tested for serological and physiological characteristics. Because the serological reactions of these strains varied, a differentiation scheme could not be based on these reactions. For the same reason, there could be no correlation of serological characteristics with physiological characteristics. Nearly 97% of the clinical isolates were speciated by differences in physiological characteristics. Ten different physiological species were recognized. The physiological speciation scheme was based on stable enzymatic reactions rather than on results of tolerance tests. The study included air-tolerant anaerobic streptococcal strains as well as viridans streptococcal strains not normally found in humans. The differentiation scheme and nomenclature of the author are related to those of other investigators. Differences in the distribution of species isolated from different clinical sources and human infections were also noted. A key for the differentiation of human isolates of viridans streptococci is proposed. PMID:845245

  11. Gene flow and population differentiation.

    PubMed

    Endler, J A

    1973-01-19

    There are many possible spatial patterns of selection and gene flow that can produce a given cline structure; the actual geography of natural selection and gene flow must be worked out before an attempt is made to explain a given natural cline in terms of a model. The results of experimental and theoretical models show that it is possible for local differentiation to evolve parapatrically in spite of considerable gene flow if the selection gradients are relatively uniform. Irregularities in environmental gradients increase the sensitivity of clines to the effects of gene flow in proportion to the increase in the differences in gene frequencies between the emigrants and the demes receiving the immigrants. It is not necessary for a sharp spatial environmental change to be present for distinct differentiation to occur. In some cases even a gentle environmental gradient can give rise to marked spatial differentiation along a genetically continuous series of demes; such environmental differences may be below the practical limits of resolution in field studies. Any asymmetry in gene flow does not lead to dedifferentiation if the environmental gradient is smooth; it merely shifts the position of the transition zone between the differentiated areas from that which would be expected if there were no asymmetry. Abrupt geographic differences in gene, genotype, or morph frequencies should not, therefore, be interpreted as evidence for environmental changes in the immediate vicinity of the steepest part of the cline; neither should they be interpreted as evidence for geographic barriers, sharp environmental differences, or sexual isolation among the differentiated groups of populations when there are no other sources of evidence for these phenomena. Gene flow may be unimportant in the differentiation of populations along environmental gradients.

  12. Thinking Differentially: A Response to Issues in Differential Response

    ERIC Educational Resources Information Center

    Fluke, John D.; Merkel-Holguin, Lisa; Schene, Patricia

    2013-01-01

    This is a response to the document by Hughes et al. in this issue that offers a critique of the status of differential response (DR). We find the document to be helpful in intent, but do not find that it reflects scientifically sound methods, and contains many mischaracterizations of the status, impetus, research, and evaluation of DR to date. We…

  13. Differential geometry techniques for sets of nonlinear partial differential equations

    NASA Technical Reports Server (NTRS)

    Estabrook, Frank B.

    1990-01-01

    An attempt is made to show that the Cartan theory of partial differential equations can be a useful technique for applied mathematics. Techniques for finding consistent subfamilies of solutions that are generically rich and well-posed and for introducing potentials or other usefully consistent auxiliary fields are introduced. An extended sample calculation involving the Korteweg-de Vries equation is given.

  14. Moment of Inertia by Differentiation

    NASA Astrophysics Data System (ADS)

    Rizcallah, Joseph A.

    2015-11-01

    The calculation of the moment of inertia of an extended body, as presented in standard introductory-level textbooks, involves the evaluation of a definite integral—an operation often not fully mastered by beginners, let alone the conceptual difficulties it presents, even to the advanced student, in understanding and setting up the integral in the first place. We here use dimensional analysis along with elementary differentiation techniques to derive the moments of inertia of various extended bodies. The suggested method does not employ integrals and, in effect, is just a disguised application of elementary ordinary differential equations.

  15. Phase tracking with differential dispersion

    NASA Astrophysics Data System (ADS)

    Haubois, Xavier; Lacour, Sylvestre; Perrin, Guy S.; Dembet, Roderick; Fedou, Pierre; Eisenhauer, Frank; Rousselet-Perraut, Karine; Straubmeier, Christian; Amorim, Antonio; Brandner, Wolfgang

    2014-07-01

    Differential chromatic dispersion in single-mode optical fibres leads to a loss of contrast of the white light fringe. For the GRAVITY instrument, this aspect is critical since it limits the fringe tracking performance. We present a real-time algorithm that compensates for differential dispersion due to varying fibre lengths using prior calibration of the optical fibres. This correction is limited by the accuracy to which the fibres stretch is known. We show how this affects the SNR on the white light fringe for different scenarios and we estimate how this phenomenon might eventually impact the astrometric accuracy of GRAVITY observations.

  16. Differential Seismic Modeling of Stars

    NASA Astrophysics Data System (ADS)

    Ozel, N.; Mosser, B.; Dupret, M.-A.; Bruntt, H.; Barban, C.; Deheuvels, S.; García, R. A.; Michel, E.; Samadi, R.; Baudin, F.; Régulo, C.; Auvergne, M.; Baglin, A.; Catala, C.; Morel, P.; Pichon, B.

    2013-12-01

    CoRoT (Convection Rotation and planetary Transits) observations provide the opportunity to study a large sample of stars ranging from the Main Sequence (MS) to the Red Giant Branch. With the large increase in the number of stars showing solar-like oscillations, we intend to extract as much information as possible from a low signal-to-noise ratio (SNR) oscillation spectrum, benefiting from comparison with a reference star having similar seismic and fundamental parameters. We propose a differential method to determine stellar properties of solar-like oscillations which we call “differential seismology of stellar twins”.

  17. Differentiating neoplasms of hair germ

    PubMed Central

    Headington, J. T.

    1970-01-01

    Differentiating neoplasms of hair germ are benign epithelial-mesenchymal tumours of skin in which hair follicle development may be partly or completely recapitulated. The epithelial component is equivalent to the hair germ. The mesenchymal component is equivalent to the dermal papilla. Epithelial-mesenchymal interaction results in the morphogenesis of hair follicles. In neoplasms showing stromal induction, there is centrifugal organizations: hair bulbs are found at the periphery of tumour lobules and hairs are projected centrally to lie within small keratinizing cysts. Neoplasms of hair germ without advanced morpho-differentiation are termed `trichoblastomas', and those neoplasms in which hair follicle development is advanced are called `trichogenic trichoblastomas'. Images PMID:5476873

  18. 5 CFR 532.511 - Environmental differentials.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Environmental differentials. 532.511... PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a) Entitlements to environmental differential pay.(1) In accordance with section 5343(c)(4) of title 5, United...

  19. 5 CFR 532.511 - Environmental differentials.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Environmental differentials. 532.511... PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a) Entitlements to environmental differential pay.(1) In accordance with section 5343(c)(4) of title 5, United...

  20. On abstract degenerate neutral differential equations

    NASA Astrophysics Data System (ADS)

    Hernández, Eduardo; O'Regan, Donal

    2016-10-01

    We introduce a new abstract model of functional differential equations, which we call abstract degenerate neutral differential equations, and we study the existence of strict solutions. The class of problems and the technical approach introduced in this paper allow us to generalize and extend recent results on abstract neutral differential equations. Some examples on nonlinear partial neutral differential equations are presented.

  1. 5 CFR 532.511 - Environmental differentials.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Environmental differentials. 532.511... PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a) Entitlements to environmental differential pay.(1) In accordance with section 5343(c)(4) of title 5, United...

  2. 5 CFR 532.511 - Environmental differentials.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Environmental differentials. 532.511... PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a) Entitlements to environmental differential pay.(1) In accordance with section 5343(c)(4) of title 5, United...

  3. Experiments with a differential transformer

    NASA Astrophysics Data System (ADS)

    Munguía Aguilar, Horacio

    2016-11-01

    An experiment with an electric transformer based on single coils shows how electromagnetic induction changes when the magnetic coupling between coils is adjusted. This transformer has two secondary outputs which are taken differentially. This is the basis for a widely used position transducer known as LVDT.

  4. Experiments with a Differential Transformer

    ERIC Educational Resources Information Center

    Aguilar, Horacio Munguía

    2016-01-01

    An experiment with an electric transformer based on single coils shows how electromagnetic induction changes when the magnetic coupling between coils is adjusted. This transformer has two secondary outputs which are taken differentially. This is the basis for a widely used position transducer known as LVDT.

  5. Metabolic reprogramming during neuronal differentiation.

    PubMed

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-09-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  6. Making the Case for Differentiation

    ERIC Educational Resources Information Center

    Birnie, Billie F.

    2015-01-01

    Three misconceptions about differentiated instruction prevent some teachers from using it: it is just another new fad that will fade away; it requires a separate lesson plan for every student; and it is not worth the effort. Examining those ideas through the perspectives of actual teaching experience and sound research proves them to be just what…

  7. Differentiated Instruction in the Classroom

    ERIC Educational Resources Information Center

    Kelly, Gretchen

    2013-01-01

    Low achievement on standardized tests may be attributed to many factors, including teaching methods. Differentiated instruction has been identified as a teaching method using different learning modalities that appeal to varied student interests with individualized instruction. The purpose of this quantitative study was to compare whole-group…

  8. Pendulum Motion and Differential Equations

    ERIC Educational Resources Information Center

    Reid, Thomas F.; King, Stephen C.

    2009-01-01

    A common example of real-world motion that can be modeled by a differential equation, and one easily understood by the student, is the simple pendulum. Simplifying assumptions are necessary for closed-form solutions to exist, and frequently there is little discussion of the impact if those assumptions are not met. This article presents a…

  9. Metabolic reprogramming during neuronal differentiation

    PubMed Central

    Agostini, M; Romeo, F; Inoue, S; Niklison-Chirou, M V; Elia, A J; Dinsdale, D; Morone, N; Knight, R A; Mak, T W; Melino, G

    2016-01-01

    Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate–glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K–Akt–mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation. PMID:27058317

  10. Multiple Intelligences for Differentiated Learning

    ERIC Educational Resources Information Center

    Williams, R. Bruce

    2007-01-01

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

  11. Ordinary Differential Equation System Solver

    1992-03-05

    LSODE is a package of subroutines for the numerical solution of the initial value problem for systems of first order ordinary differential equations. The package is suitable for either stiff or nonstiff systems. For stiff systems the Jacobian matrix may be treated in either full or banded form. LSODE can also be used when the Jacobian can be approximated by a band matrix.

  12. Solving Nonlinear Coupled Differential Equations

    NASA Technical Reports Server (NTRS)

    Mitchell, L.; David, J.

    1986-01-01

    Harmonic balance method developed to obtain approximate steady-state solutions for nonlinear coupled ordinary differential equations. Method usable with transfer matrices commonly used to analyze shaft systems. Solution to nonlinear equation, with periodic forcing function represented as sum of series similar to Fourier series but with form of terms suggested by equation itself.

  13. Differential geometry meets the cell.

    PubMed

    Marshall, Wallace F

    2013-07-18

    A new study by Terasaki et al. highlights the role of physical forces in biological form by showing that connections between stacked endoplasmic reticulum cisternae have a shape well known in classical differential geometry, the helicoid, and that this shape is a predictable consequence of membrane physics.

  14. Examining Differentiated Instruction: Teachers Respond

    ERIC Educational Resources Information Center

    Logan, Brenda

    2011-01-01

    Today's classrooms are more diverse than ever. In fact, research shows that there will be a steady increase in Hispanic, Asian Americans, and African American students in the coming years. Therefore, differentiated instruction may be the panacea that educators are searching for. This paper commences with an introduction and then segways into a…

  15. Differentiation in the Music Classroom

    ERIC Educational Resources Information Center

    Standerfer, Stephanie L.

    2011-01-01

    Differentiating music instruction can be done well with a bit of forethought and creativity. When strategically used, music educators can better meet students' needs and make great strides in individual and overall student achievement. A variety of K-12 choral, instrumental, and general music examples is included. (Contains 7 notes and 2 tables.)

  16. Fibronectin regulates calvarial osteoblast differentiation

    NASA Technical Reports Server (NTRS)

    Moursi, A. M.; Damsky, C. H.; Lull, J.; Zimmerman, D.; Doty, S. B.; Aota, S.; Globus, R. K.

    1996-01-01

    The secretion of fibronectin by differentiating osteoblasts and its accumulation at sites of osteogenesis suggest that fibronectin participates in bone formation. To test this directly, we determined whether fibronectin-cell interactions regulate progressive differentiation of cultured fetal rat calvarial osteoblasts. Spatial distributions of alpha 5 integrin subunit, fibronectin, osteopontin (bone sialoprotein I) and osteocalcin (bone Gla-protein) were similar in fetal rat calvaria and mineralized, bone-like nodules formed by cultured osteoblasts. Addition of anti-fibronectin antibodies to cultures at confluence reduced subsequent formation of nodules to less than 10% of control values, showing that fibronectin is required for normal nodule morphogenesis. Anti-fibronectin antibodies selectively inhibited steady-state expression of mRNA for genes associated with osteoblast differentiation; mRNA levels for alkaline phosphatase and osteocalcin were suppressed, whereas fibronectin, type I collagen and osteopontin were unaffected. To identify functionally relevant domains of fibronectin, we treated cells with soluble fibronectin fragments and peptides. Cell-binding fibronectin fragments (type III repeats 6-10) containing the Arg-Gly-Asp (RGD) sequence blocked both nodule initiation and maturation, whether or not they contained a functional synergy site. In contrast, addition of the RGD-containing peptide GRGDSPK alone did not inhibit nodule initiation, although it did block nodule maturation. Thus, in addition to the RGD sequence, other features of the large cell-binding fragments contribute to the full osteogenic effects of fibronectin. Nodule formation and osteoblast differentiation resumed after anti-fibronectin antibodies or GRGDSPK peptides were omitted from the media, showing that the inhibition was reversible and the treatments were not cytotoxic. Outside the central cell-binding domain, peptides from the IIICS region and antibodies to the N terminus did not

  17. Differential attack on mini-AES

    NASA Astrophysics Data System (ADS)

    Ajeng Gemellia, Asadini Dwi; Indarjani, Santi

    2012-05-01

    This paper presents the results of differential attack on Mini-AES algorithm. The differential trails are constructed using all combinations of propagation ratio without repetition. To give practical results, we implement the key extraction for differential characteristics which have the highest and lowest probability as a comparison. Based on total propagation ratio and complexity resulted, Mini-AES algorithms are vulnerable to differential attack. The best differential characteristic is the differential characteristic using a single active s-box with the propagation ratio of 8 / 16.

  18. Differential Equations for Morphological Amoebas

    NASA Astrophysics Data System (ADS)

    Welk, Martin; Breuß, Michael; Vogel, Oliver

    This paper is concerned with amoeba median filtering, a structure-adaptive morphological image filter. It has been introduced by Lerallut et al. in a discrete formulation. Experimental evidence shows that iterated amoeba median filtering leads to segmentation-like results that are similar to those obtained by self-snakes, an image filter based on a partial differential equation. We investigate this correspondence by analysing a space-continuous formulation of iterated median filtering. We prove that in the limit of vanishing radius of the structuring elements, iterated amoeba median filtering indeed approximates a partial differential equation related to self-snakes and the well-known (mean) curvature motion equation. We present experiments with discrete iterated amoeba median filtering that confirm qualitative and quantitative predictions of our analysis.

  19. Three-color differential interferometry.

    PubMed

    Desse, J M

    1997-10-01

    It is shown that differential interferometry using a Wollaston prism and a three-color laser source is an optical technique that has all the advantages of differential interferometry in polarized white light and of classical monochromatic interferometry. The interference fringe pattern obtained is very large and colored and presents a central white fringe that enables easy identification of the zero order of the interferogram. The three-color source is obtained by filtering the unwanted lines of the ionized laser (mixed argon and krypton) and balancing the three red, green, and blue lines by a technique that involves placing birefringent plates between the polarizer and the analyzer, the thickness of which has been calculated to create a natural filter. The unsteady aerodynamic flow downstream of a diamond shape airfoil has been visualized with this technique, which shows that the power of the light source is sufficient to record the interferograms at a high rate. PMID:18264221

  20. Three-color differential interferometry.

    PubMed

    Desse, J M

    1997-10-01

    It is shown that differential interferometry using a Wollaston prism and a three-color laser source is an optical technique that has all the advantages of differential interferometry in polarized white light and of classical monochromatic interferometry. The interference fringe pattern obtained is very large and colored and presents a central white fringe that enables easy identification of the zero order of the interferogram. The three-color source is obtained by filtering the unwanted lines of the ionized laser (mixed argon and krypton) and balancing the three red, green, and blue lines by a technique that involves placing birefringent plates between the polarizer and the analyzer, the thickness of which has been calculated to create a natural filter. The unsteady aerodynamic flow downstream of a diamond shape airfoil has been visualized with this technique, which shows that the power of the light source is sufficient to record the interferograms at a high rate.

  1. [Differential diagnosis of acute arthritis].

    PubMed

    Eviltis, Egidijus

    2003-01-01

    Acute arthritis can first present as a symptom of dangerous and rapidly progressing disease. It is quite easy to differentiate between arthritis and periarthritis. More problematical is correct early differential diagnosis of the acute arthritis. Determining whether one, several or many joints are affected can narrow the diagnostic possibilities. Arthrocentesis and synovial fluid testing provide much information and should be done at initial evaluation if possible. The presence or absence of fever, rash, family history of joint disease and exposure to infective organisms can further direct diagnostic studies and treatment. In general, to avoid masking clues, drug therapy should be delayed for mild symptoms until diagnosis is complete. This article is designed mostly for primary care physicians, residents and includes author's original data and review of recommended reading. PMID:12794379

  2. Differential Optical Synthetic Aperture Radar

    DOEpatents

    Stappaerts, Eddy A.

    2005-04-12

    A new differential technique for forming optical images using a synthetic aperture is introduced. This differential technique utilizes a single aperture to obtain unique (N) phases that can be processed to produce a synthetic aperture image at points along a trajectory. This is accomplished by dividing the aperture into two equal "subapertures", each having a width that is less than the actual aperture, along the direction of flight. As the platform flies along a given trajectory, a source illuminates objects and the two subapertures are configured to collect return signals. The techniques of the invention is designed to cancel common-mode errors, trajectory deviations from a straight line, and laser phase noise to provide the set of resultant (N) phases that can produce an image having a spatial resolution corresponding to a synthetic aperture.

  3. Laser differential confocal radius measurement.

    PubMed

    Zhao, Weiqian; Sun, Ruoduan; Qiu, Lirong; Sha, Dingguo

    2010-02-01

    A new laser differential confocal radius measurement (DCRM) is proposed for high precision measurement of radius. Based on the property of an axial intensity curve that the absolute zero precisely corresponds to the focus of the objective in a differential confocal system (DCS), DCRM uses the zero point of the DCS axial intensity curve to precisely identify the cat's-eye and confocal positions of the test lens, and measures the accurate distance between the two positions to achieve the high-precision measurement of radius of curvature (ROC). In comparison with the existing measurement methods, DCRM proposed has a high measurement precision, a strong environmental anti-interference capability and a low cost. The theoretical analyses and preliminary experimental results indicate that DCRM has a relative measurement error of better than 5 ppm. PMID:20174065

  4. MULTIPLE DIFFERENTIAL ROTARY MECHANICAL DRIVE

    DOEpatents

    Smits, R.G.

    1964-01-28

    This patent relates to a mechanism suitable for such applications as driving two spaced-apart spools which carry a roll film strip under conditions where the film movement must be rapidly started, stopped, and reversed while maintaining a constant tension on the film. The basic drive is provided by a variable speed, reversible rnotor coupled to both spools through a first differential mechanism and driving both spools in the same direction. A second motor, providing a constant torque, is connected to the two spools through a second differential mechanism and is coupled to impart torque to one spool in a first direction anid to the other spool in the reverse direction thus applying a constant tension to the film passing over the two spools irrespective of the speed or direction of rotation thereof. (AEC)

  5. Airborne Differential Doppler Weather Radar

    NASA Technical Reports Server (NTRS)

    Meneghini, R.; Bidwell, S.; Liao, L.; Rincon, R.; Heymsfield, G.; Hildebrand, Peter H. (Technical Monitor)

    2001-01-01

    The Precipitation Radar aboard the Tropical Rain Measuring Mission (TRMM) Satellite has shown the potential for spaceborne sensing of snow and rain by means of an incoherent pulsed radar operating at 13.8 GHz. The primary advantage of radar relative to passive instruments arises from the fact that the radar can image the 3-dimensional structure of storms. As a consequence, the radar data can be used to determine the vertical rain structure, rain type (convective/stratiform) effective storm height, and location of the melting layer. The radar, moreover, can be used to detect snow and improve the estimation of rain rate over land. To move toward spaceborne weather radars that can be deployed routinely as part of an instrument set consisting of passive and active sensors will require the development of less expensive, lighter-weight radars that consume less power. At the same time, the addition of a second frequency and an upgrade to Doppler capability are features that are needed to retrieve information on the characteristics of the drop size distribution, vertical air motion and storm dynamics. One approach to the problem is to use a single broad-band transmitter-receiver and antenna where two narrow-band frequencies are spaced apart by 5% to 10% of the center frequency. Use of Ka-band frequencies (26.5 GHz - 40 GHz) affords two advantages: adequate spatial resolution can be attained with a relatively small antenna and the differential reflectivity and mean Doppler signals are directly related to the median mass diameter of the snow and raindrop size distributions. The differential mean Doppler signal has the additional property that this quantity depends only on that part of the radial speed of the hydrometeors that is drop-size dependent. In principle, the mean and differential mean Doppler from a near-nadir viewing radar can be used to retrieve vertical air motion as well as the total mean radial velocity. In the paper, we present theoretical calculations for the

  6. Osteoblast Differentiation at a Glance

    PubMed Central

    Rutkovskiy, Arkady; Stensløkken, Kåre-Olav; Vaage, Ingvar Jarle

    2016-01-01

    Ossification is a tightly regulated process, performed by specialized cells called osteoblasts. Dysregulation of this process may cause inadequate or excessive mineralization of bones or ectopic calcification, all of which have grave consequences for human health. Understanding osteoblast biology may help to treat diseases such as osteogenesis imperfecta, calcific heart valve disease, osteoporosis, and many others. Osteoblasts are bone-building cells of mesenchymal origin; they differentiate from mesenchymal progenitors, either directly or via an osteochondroprogenitor. The direct pathway is typical for intramembranous ossification of the skull and clavicles, while the latter is a hallmark of endochondral ossification of the axial skeleton and limbs. The pathways merge at the level of preosteoblasts, which progress through 3 stages: proliferation, matrix maturation, and mineralization. Osteoblasts can also differentiate into osteocytes, which are stellate cells populating narrow interconnecting passages within the bone matrix. The key molecular switch in the commitment of mesenchymal progenitors to osteoblast lineage is the transcription factor cbfa/runx2, which has multiple upstream regulators and a wide variety of targets. Upstream is the Wnt/Notch system, Sox9, Msx2, and hedgehog signaling. Cofactors of Runx2 include Osx, Atf4, and others. A few paracrine and endocrine factors serve as coactivators, in particular, bone morphogenetic proteins and parathyroid hormone. The process is further fine-tuned by vitamin D and histone deacetylases. Osteoblast differentiation is subject to regulation by physical stimuli to ensure the formation of bone adequate for structural and dynamic support of the body. Here, we provide a brief description of the various stimuli that influence osteogenesis: shear stress, compression, stretch, micro- and macrogravity, and ultrasound. A complex understanding of factors necessary for osteoblast differentiation paves a way to introduction

  7. Studies of gonadal sex differentiation

    PubMed Central

    Makiyan, Zograb

    2016-01-01

    ABSTRACT Gonadal differentiation has a determinative influence on sex development in human embryos. Disorders of sexual development (DSD) have been associated with persistent embryonal differentiation stages. Between 1998 and 2015, 139 female patients with various (DSD) underwent operations at the Scientific Center of Obstetrics, Gynaecology and Perynatology in Moscow, Russia. Clinical investigations included karyotyping, ultrasound imaging, hormonal measurement and investigations of gonadal morphology. The male characteristics in the embryo are imposed by testicular hormones. When these are absent or inactive, the fetus may be arrested at between developmental stages, or stay on indifferent stage and become phenotypically female. A systematic analysis of gonadal morphology in DSD patients and a literature review revealed some controversies and led us to formulate a new hypothesis about sex differentiation. Proliferation of the mesonephric system (tubules and corpuscles) in the gonads stimulates the masculinization of gonads to testis. Sustentacular Sertoli cells of the testes are derived from mesonephric excretory tubules, while interstitial Leydig cells are derived from the original mesenchyme of the mesonephros. According of the new hypothesis, the original mesonephric cells (tubules and corpuscles) potentially persist in the ovarian parenchyma. In female gonads, some mesonephric excretory tubules regress and lose the tubular structure, but form ovarian theca interna and externa, becoming analogous to the sustentacular Sertoli cells in the testis. The ovarian interstitial Leydig cells are derived from intertubal mesenchyme of the mesonephros, similar to what occurs in male gonads (testis). Surprisingly, the leading determinative factor in sexual differentiation of the gonads is the mesonephros, represented by the embryonic urinary system. PMID:26950283

  8. Erotic gender differentiation in pedophilia.

    PubMed

    Freund, K; Watson, R; Dickey, R; Rienzo, D

    1991-12-01

    Five groups of males were compared on penile volume changes elicited from viewing short movie strips and slides of nude children and adults of both genders. Subject groups were sex offenders against adult females, volunteer controls who erotically preferred adult females, volunteer controls who erotically preferred adult males, heterosexual pedophiles, and homosexual pedophiles. Pedophiles differentiated erotically between females and males less than males who erotically preferred physically mature partners. PMID:1768222

  9. Differential scanning calorimetry of coal

    NASA Technical Reports Server (NTRS)

    Gold, P. I.

    1978-01-01

    Differential scanning calorimetry studies performed during the first year of this project demonstrated the occurrence of exothermic reactions associated with the production of volatile matter in or near the plastic region. The temperature and magnitude of the exothermic peak were observed to be strongly affected by the heating rate, sample mass and, to a lesser extent, by sample particle size. Thermal properties also were found to be influenced by oxidation of the coal sample due to weathering effects.

  10. Synovial Sarcoma With Myoid Differentiation.

    PubMed

    Qassid, Omar; Ali, Ahmed; Thway, Khin

    2016-09-01

    Synovial sarcoma is a malignant mesenchymal tumor with variable epithelial differentiation, which is defined by the presence of a specific t(X;18)(p11.2;q11.2) chromosomal translocation that generates SS18-SSX fusion oncogenes. Synovial sarcoma typically arises within extremity deep soft tissue (particularly around large joints) of young adults, but has been shown to occur at almost any location. When it arises in more unusual sites, such as the abdomen, it can present a significant diagnostic challenge. We describe a case of intraabdominal monophasic synovial sarcoma that immunohistochemically showed strong expression of smooth muscle actin and calponin but only very scanty cytokeratin, and which showed morphologic and immunohistochemical overlap with other spindle cell neoplasms that can arise at this site, such as gastrointestinal stromal tumor and myofibrosarcoma. As correct diagnosis is of clinical and prognostic importance, surgical pathologists should be aware of the potential for synovial sarcoma to occur at a variety of anatomic sites and of its spectrum of immunoreactivity. Synovial sarcoma should be in the differential diagnosis of spindle cell neoplasms with myoid differentiation that do not fall into any definite tumor category, for which there should be a relatively low threshold for performing fluorescence in situ hybridization or reverse transcription-polymerase chain reaction to assess for the specific SS18 gene rearrangement or SS18-SSX fusion transcripts, which remain the diagnostic gold standard. PMID:27106779

  11. Differential morphology and image processing.

    PubMed

    Maragos, P

    1996-01-01

    Image processing via mathematical morphology has traditionally used geometry to intuitively understand morphological signal operators and set or lattice algebra to analyze them in the space domain. We provide a unified view and analytic tools for morphological image processing that is based on ideas from differential calculus and dynamical systems. This includes ideas on using partial differential or difference equations (PDEs) to model distance propagation or nonlinear multiscale processes in images. We briefly review some nonlinear difference equations that implement discrete distance transforms and relate them to numerical solutions of the eikonal equation of optics. We also review some nonlinear PDEs that model the evolution of multiscale morphological operators and use morphological derivatives. Among the new ideas presented, we develop some general 2-D max/min-sum difference equations that model the space dynamics of 2-D morphological systems (including the distance computations) and some nonlinear signal transforms, called slope transforms, that can analyze these systems in a transform domain in ways conceptually similar to the application of Fourier transforms to linear systems. Thus, distance transforms are shown to be bandpass slope filters. We view the analysis of the multiscale morphological PDEs and of the eikonal PDE solved via weighted distance transforms as a unified area in nonlinear image processing, which we call differential morphology, and briefly discuss its potential applications to image processing and computer vision.

  12. Integrated Information and State Differentiation

    PubMed Central

    Marshall, William; Gomez-Ramirez, Jaime; Tononi, Giulio

    2016-01-01

    Integrated information (Φ) is a measure of the cause-effect power of a physical system. This paper investigates the relationship between Φ as defined in Integrated Information Theory and state differentiation (D), the number of, and difference between potential system states. Here we provide theoretical justification of the relationship between Φ and D, then validate the results using a simulation study. First, we show that a physical system in a state with high Φ necessarily has many elements and specifies many causal relationships. Furthermore, if the average value of integrated information across all states is high, the system must also have high differentiation. Next, we explore the use of D as a proxy for Φ using artificial networks, evolved to have integrated structures. The results show a positive linear relationship between Φ and D for multiple network sizes and connectivity patterns. Finally we investigate the differentiation evoked by sensory inputs and show that, under certain conditions, it is possible to estimate integrated information without a direct perturbation of its internal elements. In concluding, we discuss the need for further validation on larger networks and explore the potential applications of this work to the empirical study of consciousness, especially concerning the practical estimation of Φ from neuroimaging data. PMID:27445896

  13. Differential growth of wrinkled biofilms

    NASA Astrophysics Data System (ADS)

    Espeso, D. R.; Carpio, A.; Einarsson, B.

    2015-02-01

    Biofilms are antibiotic-resistant bacterial aggregates that grow on moist surfaces and can trigger hospital-acquired infections. They provide a classical example in biology where the dynamics of cellular communities may be observed and studied. Gene expression regulates cell division and differentiation, which affect the biofilm architecture. Mechanical and chemical processes shape the resulting structure. We gain insight into the interplay between cellular and mechanical processes during biofilm development on air-agar interfaces by means of a hybrid model. Cellular behavior is governed by stochastic rules informed by a cascade of concentration fields for nutrients, waste, and autoinducers. Cellular differentiation and death alter the structure and the mechanical properties of the biofilm, which is deformed according to Föppl-Von Kármán equations informed by cellular processes and the interaction with the substratum. Stiffness gradients due to growth and swelling produce wrinkle branching. We are able to reproduce wrinkled structures often formed by biofilms on air-agar interfaces, as well as spatial distributions of differentiated cells commonly observed with B. subtilis.

  14. Differentially Private Frequent Subgraph Mining

    PubMed Central

    Xu, Shengzhi; Xiong, Li; Cheng, Xiang; Xiao, Ke

    2016-01-01

    Mining frequent subgraphs from a collection of input graphs is an important topic in data mining research. However, if the input graphs contain sensitive information, releasing frequent subgraphs may pose considerable threats to individual's privacy. In this paper, we study the problem of frequent subgraph mining (FGM) under the rigorous differential privacy model. We introduce a novel differentially private FGM algorithm, which is referred to as DFG. In this algorithm, we first privately identify frequent subgraphs from input graphs, and then compute the noisy support of each identified frequent subgraph. In particular, to privately identify frequent subgraphs, we present a frequent subgraph identification approach which can improve the utility of frequent subgraph identifications through candidates pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support derivation approach, where a series of methods has been proposed to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that our DFG algorithm satisfies ε-differential privacy. Extensive experimental results on real datasets show that the DFG algorithm can privately find frequent subgraphs with high data utility.

  15. Optimal control of motorsport differentials

    NASA Astrophysics Data System (ADS)

    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.

  16. Etiopathogenesis of Differentiated Thyroid Carcinomas

    PubMed Central

    Makazlieva, Tanja; Vaskova, Olivija; Majstorov, Venjamin

    2016-01-01

    INTRODUCTION: Thyroid malignomas are a heterogeneous group of neoplasm consisting of most frequent differentiated encountered carcinomas, papillary and follicular thyroid carcinoma, then medullary thyroid carcinoma originating from neuroendocrine calcitonin-producing C-cells and rare forms of thyroid lymphomas arising from intrathyroidal lymphatic tissue, thyroid sarcomas and poorly differentiated anaplastic thyroid carcinoma. There are increasing numbers of epidemiological studies and publications that have suggested increased incidence rate of thyroid carcinomas. We have read, analysed and compare available reviews and original articles investigating different etiological factors in the development of thyroid carcinomas through Google Scholar and PubMed Database. DISCUSSION: Aetiology involved in the development of thyroid carcinomas is multifactorial and includes external influences, as well as constitutional predispositions and genetic etiological factors. The actual effect of environmental and constitutional factors is on promoting genetic and epigenetic alterations which result in cell proliferation and oncogenesis. Until now are identified numerous genetic alterations, assumed to have an important role in oncogenesis, with MAPK and PI3K-AKT as crucial signalling networks regulating growth, proliferation, differentiation and cell survival/apoptosis. CONCLUSION: This new molecular insight could have a crucial impact on diagnosis and also on improving and selecting an appropriate treatment to the patients with thyroid malignancies. PMID:27703585

  17. Differentially Private Frequent Subgraph Mining

    PubMed Central

    Xu, Shengzhi; Xiong, Li; Cheng, Xiang; Xiao, Ke

    2016-01-01

    Mining frequent subgraphs from a collection of input graphs is an important topic in data mining research. However, if the input graphs contain sensitive information, releasing frequent subgraphs may pose considerable threats to individual's privacy. In this paper, we study the problem of frequent subgraph mining (FGM) under the rigorous differential privacy model. We introduce a novel differentially private FGM algorithm, which is referred to as DFG. In this algorithm, we first privately identify frequent subgraphs from input graphs, and then compute the noisy support of each identified frequent subgraph. In particular, to privately identify frequent subgraphs, we present a frequent subgraph identification approach which can improve the utility of frequent subgraph identifications through candidates pruning. Moreover, to compute the noisy support of each identified frequent subgraph, we devise a lattice-based noisy support derivation approach, where a series of methods has been proposed to improve the accuracy of the noisy supports. Through formal privacy analysis, we prove that our DFG algorithm satisfies ε-differential privacy. Extensive experimental results on real datasets show that the DFG algorithm can privately find frequent subgraphs with high data utility. PMID:27616876

  18. Integrated Information and State Differentiation.

    PubMed

    Marshall, William; Gomez-Ramirez, Jaime; Tononi, Giulio

    2016-01-01

    Integrated information (Φ) is a measure of the cause-effect power of a physical system. This paper investigates the relationship between Φ as defined in Integrated Information Theory and state differentiation ([Formula: see text]), the number of, and difference between potential system states. Here we provide theoretical justification of the relationship between Φ and [Formula: see text], then validate the results using a simulation study. First, we show that a physical system in a state with high Φ necessarily has many elements and specifies many causal relationships. Furthermore, if the average value of integrated information across all states is high, the system must also have high differentiation. Next, we explore the use of [Formula: see text] as a proxy for Φ using artificial networks, evolved to have integrated structures. The results show a positive linear relationship between Φ and [Formula: see text] for multiple network sizes and connectivity patterns. Finally we investigate the differentiation evoked by sensory inputs and show that, under certain conditions, it is possible to estimate integrated information without a direct perturbation of its internal elements. In concluding, we discuss the need for further validation on larger networks and explore the potential applications of this work to the empirical study of consciousness, especially concerning the practical estimation of Φ from neuroimaging data. PMID:27445896

  19. Discoidin domain receptor 2 (DDR2) regulates proliferation of endochondral cells in mice

    SciTech Connect

    Kawai, Ikuma; Hisaki, Tomoka; Sugiura, Koji; Naito, Kunihiko; Kano, Kiyoshi

    2012-10-26

    Highlights: Black-Right-Pointing-Pointer Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase. Black-Right-Pointing-Pointer DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. Black-Right-Pointing-Pointer We produced in vitro and in vivo model to better understand the role of DDR2. Black-Right-Pointing-Pointer DDR2 might play an inhibitory role in the proliferation of chondrocyte. -- Abstract: Discoidin domain receptor 2 (DDR2) is a receptor tyrosine kinase that is activated by fibrillar collagens. DDR2 regulates cell proliferation, cell adhesion, migration, and extracellular matrix remodeling. The decrement of endogenous DDR2 represses osteoblastic marker gene expression and osteogenic differentiation in murine preosteoblastic cells, but the functions of DDR2 in chondrogenic cellular proliferation remain unclear. To better understand the role of DDR2 signaling in cellular proliferation in endochondral ossification, we inhibited Ddr2 expression via the inhibitory effect of miRNA on Ddr2 mRNA (miDdr2) and analyzed the cellular proliferation and differentiation in the prechondrocyte ATDC5 cell lines. To investigate DDR2's molecular role in endochondral cellular proliferation in vivo, we also produced transgenic mice in which the expression of truncated, kinase dead (KD) DDR2 protein is induced, and evaluated the DDR2 function in cellular proliferation in chondrocytes. Although the miDdr2-transfected ATDC5 cell lines retained normal differentiation ability, DDR2 reduction finally promoted cellular proliferation in proportion to the decreasing ratio of Ddr2 expression, and it also promoted earlier differentiation to cartilage cells by insulin induction. The layer of hypertrophic chondrocytes in KD Ddr2 transgenic mice was not significantly thicker than that of normal littermates, but the layer of proliferative chondrocytes in KD-Ddr2 transgenic mice was significantly thicker than that of normal littermates

  20. Differentiator design and performance for edge sharpening

    USGS Publications Warehouse

    Pan, Jeng-Jong; Domingue, Julia O.

    1990-01-01

    A two-dimensional differentiator is useful for edge sharpening in digital image processing. In the design of a differentiator, differentiator coefficients that satisfy the specification of frequency response must be approximated. Four mathematical techniques - the minimax method, least-squares method, nonlinear programming, and linear programming - can be applied to solve the approximation problem. Results indicated that the differentiator derived from linear programming gives the highest resolution. -from Authors

  1. Numerical Differentiation of Noisy, Nonsmooth Data

    DOE PAGES

    Chartrand, Rick

    2011-01-01

    We consider the problem of differentiating a function specified by noisy data. Regularizing the differentiation process avoids the noise amplification of finite-difference methods. We use total-variation regularization, which allows for discontinuous solutions. The resulting simple algorithm accurately differentiates noisy functions, including those which have a discontinuous derivative.

  2. Differential Fee: From Conceptualisation to Implementation.

    ERIC Educational Resources Information Center

    Ng, Todd C. Y.; Wong, Andrew L. S.

    A differential fee policy was adopted at the Open Learning Institute (OLI) of Hong Kong after a process of conceptualization, planning, proposal, approval and implementation. Under the differential fee policy different tuition rates were charged for different courses. The differential fee policy was conceptualized at OLI based on economics,…

  3. Differentiation: A Strategic Response to Student Needs

    ERIC Educational Resources Information Center

    Hedrick, Kelly A.

    2012-01-01

    Virginia Beach City Public Schools had decided to embrace differentiation as its philosophy of instruction. Differentiation was added to the teacher evaluation rubric, and by 2003 Virginia Beach launched full force into a division-wide focus on Carol Ann Tomlinson's model for differentiation. (Tomlinson is the author of several books on the…

  4. Teaching Differentials in Thermodynamics Using Spatial Visualization

    ERIC Educational Resources Information Center

    Wang, Chih-Yueh; Hou, Ching-Han

    2012-01-01

    The greatest difficulty that is encountered by students in thermodynamics classes is to find relationships between variables and to solve a total differential equation that relates one thermodynamic state variable to two mutually independent state variables. Rules of differentiation, including the total differential and the cyclic rule, are…

  5. Differentiated Instruction: Making Informed Teacher Decisions

    ERIC Educational Resources Information Center

    Watts-Taffe, Susan; Laster, B. P.; Broach, Laura; Marinak, Barbara; Connor, Carol McDonald; Walker-Dalhouse, Doris

    2013-01-01

    This article addresses approaches to differentiating instruction to meet the needs of students whose literacy needs, interests, and strengths vary widely. This article was designed to support classroom teachers who understand the importance of differentiating instruction, but are unsure of how best to design and implement differentiation within…

  6. Valuing the Advanced Learner: Differentiating up

    ERIC Educational Resources Information Center

    Manning, Sandra; Stanford, Barbara; Reeves, Stacy

    2010-01-01

    In today's educational climate, differentiated instruction is a common practice for students who need remediation; what is less common is to Differentiate Instruction for the advanced learner. Contrary to popular perceptions, advanced learners do not automatically differentiate instruction on their own. Students who have the potential to excel…

  7. In Vitro Th Differentiation Protocol.

    PubMed

    Sekiya, Takashi; Yoshimura, Akihiko

    2016-01-01

    CD4(+) T cells play central roles in adaptive immunity, driving appropriate immune responses to invading pathogens of diverse types. Four major CD4(+) T cell subsets, Th1, Th2, Th17, and Treg cells are differentiated from naïve CD4(+) T cells upon ligation of their T cell receptors with antigens, depending on the cytokines they receive. Th1 cells, which are induced by IL-12 and IFN-γ, mediate host defense against intracellular pathogens by exclusively expressing IFN-γ. Th2 cells, which are induced by IL4, secrete IL-4, IL-5, and IL-13, and protect hosts from helminths. IL-6 plus TGF-β induces Th17 cells, another Th subset identified relatively recently, express IL-17 and play important roles in the eradication of extracellular bacteria and fungi. Treg cells, which play central roles in immune suppression, are composed of either thymus-derived Treg cells (tTreg cells), which are directly developed from CD4-single positive (CD4-SP) cells in the thymus, or peripherally derived Treg cells (pTreg cells), which are induced by TGF-β plus IL-2 from naïve CD4(+) T cells. Although the regulated induction of Th cells results in proper eradication of pathogens, their excess activation results in various immune-associated diseases. For example, aberrant activation of Th1 and Th17 has been implicated in autoimmune diseases, excess Th2 activity causes atopic diseases, and impaired function of Treg cells due to abrogation of Foxp3 has been shown to cause fatal inflammatory disorders both in human and in mouse. The methods for in vitro differentiation of each Th subset described above are presented here. We hope these methods will facilitate understanding of differentiation and function of CD4(+) T cells and pathogenesis of various inflammatory diseases. PMID:26520124

  8. Nonferromagnetic linear variable differential transformer

    DOEpatents

    Ellis, James F.; Walstrom, Peter L.

    1977-06-14

    A nonferromagnetic linear variable differential transformer for accurately measuring mechanical displacements in the presence of high magnetic fields is provided. The device utilizes a movable primary coil inside a fixed secondary coil that consists of two series-opposed windings. Operation is such that the secondary output voltage is maintained in phase (depending on polarity) with the primary voltage. The transducer is well-suited to long cable runs and is useful for measuring small displacements in the presence of high or alternating magnetic fields.

  9. Non-differentiable variational principles

    NASA Astrophysics Data System (ADS)

    Cresson, Jacky

    2005-07-01

    We develop a calculus of variations for functionals which are defined on a set of non-differentiable curves. We first extend the classical differential calculus in a quantum calculus, which allows us to define a complex operator, called the scale derivative, which is the non-differentiable analogue of the classical derivative. We then define the notion of extremals for our functionals and obtain a characterization in term of a generalized Euler-Lagrange equation. We finally prove that solutions of the Schrödinger equation can be obtained as extremals of a non-differentiable variational principle, leading to an extended Hamilton's principle of least action for quantum mechanics. We compare this approach with the scale relativity theory of Nottale, which assumes a fractal structure of space-time.Résumé (Principes variationnels non différentiable). Nous développons un calcul des variations pour des fonctionnelles définies sur un ensemble de courbes non différentiables. Pour cela, nous étendons le calcul différentiel classique, en calcul appelé calcul quantique, qui nous permet de définir un opérateur à valeur complexes, appelé dérivée d'échelle, qui est l'analogue non différentiable de la dérivée usuelle. On définit alors la notion d'extremale pour ces fonctionnelles pour lesquelles nous obtenons une caractérisation via une équation d'Euler-Lagrange généralisée. On prouve enfin que les solutions de l'équation de Schrödinger peuvent s'obtenir comme solution d'un problème variationnel non différentiable, étendant ainsi le principe de moindre action de Hamilton au cadre de la mécanique quantique. On discute enfin la connexion entre ce travail et la théorie de la relativité d'échelle développée par Nottale, et qui suppose une structure fractale de l'espace-temps.

  10. Differential photometry of magnetic faculae

    NASA Technical Reports Server (NTRS)

    Foukal, P.; Duvall, T., Jr.

    1985-01-01

    New observations extending the differential continuum photometry technique to the near-infrared are presented which demonstrate that the main factor determining the facular visibility near the solar disk center is the difference in H(-) opacity (and thus in penetration depth) between the continuum passbands. It is shown how the difference signal obtained depends on the temperature gradient difference between the two faculae and photosphere. The measured facular temperature gradient is compared with that given by empirical facular models based on Fraunhofer line observations, and with theoretical predictions. An explanation for the enhanced visibility of faculae against granular noise in the difference signal is suggested.

  11. [The differential diagnosis of tenosynovitis].

    PubMed

    Brulhart, Laure; Gabay, Cem

    2011-03-16

    Etymologically a ténosynovites means inflammation of a tendon sheath. We recognize two separate presentations: exsudative and stenosing. The wide differential diagnosis includes infections, most of chronic inflammatory joint diseases, mainly connective tissue disorders, rheumatoid and psoriatic arthritis, pathology related to mechanical stress as De Quervain's tenosynovitis or trigger finger and unusually tumor. Diabetes is a risk factor for most of them and is related to poor prognosis. Musculoskeletal ultrasound is useful for diagnosis and to guide procedure as fluid aspiration or steroid injection. PMID:21510342

  12. HONO measurement by differential photolysis

    NASA Astrophysics Data System (ADS)

    Reed, Chris; Brumby, Charlotte A.; Crilley, Leigh R.; Kramer, Louisa J.; Bloss, William J.; Seakins, Paul W.; Lee, James D.; Carpenter, Lucy J.

    2016-06-01

    Nitrous acid (HONO) has been quantitatively measured in situ by differential photolysis at 385 and 395 nm, and subsequent detection as nitric oxide (NO) by the chemiluminescence reaction with ozone (O3). The technique has been evaluated by Fourier transform infrared (FT-IR) spectroscopy to provide a direct HONO measurement in a simulation chamber and compared side by side with a long absorption path optical photometer (LOPAP) in the field. The NO-O3 chemiluminescence technique is robust, well characterized, and capable of sampling at low pressure, whilst solid-state converter technology allows for unattended in situ HONO measurements in combination with fast time resolution and response.

  13. Scenario Generation Using Differential Scenario Information

    NASA Astrophysics Data System (ADS)

    Makino, Masayuki; Ohnishi, Atsushi

    A method of generating scenarios using differential scenaro information is presented. Behaviors of normal scenarios of similar purpose are quite similar each other, while actors and data in scenarios are different among these scenarios. We derive the differential information between them and apply the differential information to generate new alternative/exceptional scenarios. Our method will be illustrated with examples. This paper describes (1) a language for describing scenarios based on a simple case grammar of actions, (2) introduction of the differential scenario, and (3) method and examples of scenario generation using the differential scenario.

  14. Approximate controllability of nonlinear impulsive differential systems

    NASA Astrophysics Data System (ADS)

    Sakthivel, R.; Mahmudov, N. I.; Kim, J. H.

    2007-08-01

    Many practical systems in physical and biological sciences have impulsive dynamical be- haviours during the evolution process which can be modeled by impulsive differential equations. This paper studies the approximate controllability issue for nonlinear impulsive differential and neutral functional differential equations in Hilbert spaces. Based on the semigroup theory and fixed point approach, sufficient conditions for approximate controllability of impulsive differential and neutral functional differential equations are established. Finally, two examples are presented to illustrate the utility of the proposed result. The results improve some recent results.

  15. Nonaxisymmetric oscillations of differentially rotating relativistic stars

    SciTech Connect

    Passamonti, Andrea; Stavridis, Adamantios; Kokkotas, Kostas D.

    2008-01-15

    Nonaxisymmetric oscillations of differentially rotating stars are studied using both slow rotation and Cowling approximation. The equilibrium stellar models are relativistic polytropes where differential rotation is described by the relativistic j-constant rotation law. The oscillation spectrum is studied versus three main parameters: the stellar compactness M/R, the degree of differential rotation A, and the number of maximum couplings l{sub max}. It is shown that the rotational splitting of the nonaxisymmetric modes are strongly enhanced by increasing the compactness of the star and the degree of differential rotation. Finally, we investigate the relation between the fundamental quadrupole mode and the corotation band of differentially rotating stars.

  16. Scintigraphic differentiation of intrahepatic tumors

    SciTech Connect

    Creutzig, H.; Brolsch, C.; Gratz, K.; Neuhaus, P.; Muller, St.; Schober, O.; Lang, W.; Hundeshagen, H.; Pichlmayr, R.

    1984-01-01

    Intrahepatic tumors in asymptomatic patients are seen with increasing frequency. Treatment is dependent of the histology; while follicular nodular hyperplasia (FNH) and hemangiomas need no further treatment, all other tumors should be resected. In a prospective study we investigated the usefulness of two-stage scintigraphy (TSS) for the differentiation. The cholescintigraphy was started with a perfusion study, followed by a scan in the parenchymal phase and in the excretion phase. There is a typical scintigraphic pattern for FNH (hyperperfusion, normal parenchymal uptake delayed excretion) and hemangioma (hypoperfusion, no uptake), while all other tumors may have a mixed pattern. Therefore a blood pool is added to look for a hemangioma, if there is no typical pattern for FNH in the cholescintigraphy. The TSS classified correct 21 of 23 patients with FNH, 17 of 18 with hemangiomas, all 3 with adenoma and 36 of 37 with primary malignant intrahepatic tumors. The TSS is more accurate than CT or sonography, safe and inexpensive and therefore the method of first choice in the differentiation of intrahepatic tumors.

  17. [Differential diagnoses of West syndrome].

    PubMed

    Fejerman, Natalio

    2013-09-01

    This study describes the clinical and electroencephalographic characteristics of epileptic spasms, and more especially those that occur during the first two years of life (infantile spasms). West syndrome has been clearly defined as the association between infantile spasms with an electroencephalographic pattern of hypsarrhythmia. Although intellectual deficit appears in almost all cases in which infantile spasms are not controlled with medication, this is a developmental aspect of the condition and not a manifestation that must necessarily be present in order to define the syndrome. The analysis of the interictal and ictal electroencephalogram readings, together with the clinical characteristics of the spasms and the neurological examination of patients, provides some orientation as regards the causations. Despite the spectrum that the title of this work focuses on, the study does not cover the treatment of early infants with West syndrome. Emphasis is placed on the differential diagnoses of West syndrome with other epileptic syndromes that manifest in the first two years of life, and more especially with a series of abnormal non-epileptic motor phenomena that occur in early infants. All these last non-epileptic disorders are displayed in a table, but benign myoclonus of early infancy or Fejerman syndrome is given as a paradigmatic example for the differential diagnosis. The primordial aim is to prevent neurologically healthy early infants from receiving antiepileptic drugs and even adrenocorticotropic hormone or corticoids due to a mistaken diagnosis.

  18. Differentially Private Empirical Risk Minimization

    PubMed Central

    Chaudhuri, Kamalika; Monteleoni, Claire; Sarwate, Anand D.

    2011-01-01

    Privacy-preserving machine learning algorithms are crucial for the increasingly common setting in which personal data, such as medical or financial records, are analyzed. We provide general techniques to produce privacy-preserving approximations of classifiers learned via (regularized) empirical risk minimization (ERM). These algorithms are private under the ε-differential privacy definition due to Dwork et al. (2006). First we apply the output perturbation ideas of Dwork et al. (2006), to ERM classification. Then we propose a new method, objective perturbation, for privacy-preserving machine learning algorithm design. This method entails perturbing the objective function before optimizing over classifiers. If the loss and regularizer satisfy certain convexity and differentiability criteria, we prove theoretical results showing that our algorithms preserve privacy, and provide generalization bounds for linear and nonlinear kernels. We further present a privacy-preserving technique for tuning the parameters in general machine learning algorithms, thereby providing end-to-end privacy guarantees for the training process. We apply these results to produce privacy-preserving analogues of regularized logistic regression and support vector machines. We obtain encouraging results from evaluating their performance on real demographic and benchmark data sets. Our results show that both theoretically and empirically, objective perturbation is superior to the previous state-of-the-art, output perturbation, in managing the inherent tradeoff between privacy and learning performance. PMID:21892342

  19. Corridors cause differential seed predation.

    SciTech Connect

    Orrock, John L.; Damschen, Ellen I.

    2005-06-01

    Orrock, John, L., and Ellen I. Damschen. 2005. Corridors cause differential seed predation. Ecol. Apps. 15(3):793-798. Abstract. Corridors that connect disjunct populations are heavily debated in conservation, largely because the effects of corridors have rarely been evaluated by replicated, large-scale studies. Using large-scale experimental landscapes, we found that, in addition to documented positive effects, corridors also have negative impacts on bird-dispersed plants by affecting seed predation, and that overall predation is a function of the seeds primary consumer (rodents or arthropods). Both large-seeded Prunus serotina and small-seeded Rubus allegheniensis experienced greater predation in connected patches. However, P. serotina experienced significantly less seed predation compared to R. allegheniensis in unconnected patches, due to decreased impacts of rodent seed predators on this large-seeded species. Viewed in light of previous evidence that corridors have beneficial impacts by increasing pollination and seed dispersal, this work demonstrates that corridors may have both positive and negative effects for the same plant species at different life stages. Moreover, these effects may differentially affect plant species within the same community: seeds primarily consumed by rodents suffer less predation in unconnected patches. By shifting the impact of rodent and arthropod seed predators, corridors constructed for plant conservation could lead to shifts in the seed bank.

  20. Relativistic differential-difference momentum operators and noncommutative differential calculus

    SciTech Connect

    Mir-Kasimov, R. M.

    2013-09-15

    The relativistic kinetic momentum operators are introduced in the framework of the Quantum Mechanics (QM) in the Relativistic Configuration Space (RCS). These operators correspond to the half of the non-Euclidean distance in the Lobachevsky momentum space. In terms of kinetic momentum operators the relativistic kinetic energy is separated as the independent term of the total Hamiltonian. This relativistic kinetic energy term is not distinguishing in form from its nonrelativistic counterpart. The role of the plane wave (wave function of the motion with definite value of momentum and energy) plays the generating function for the matrix elements of the unitary irreps of Lorentz group (generalized Jacobi polynomials). The kinetic momentum operators are the interior derivatives in the framework of the noncommutative differential calculus over the commutative algebra generated by the coordinate functions over the RCS.

  1. Differential Geometry Based Multiscale Models

    PubMed Central

    Wei, Guo-Wei

    2010-01-01

    Large chemical and biological systems such as fuel cells, ion channels, molecular motors, and viruses are of great importance to the scientific community and public health. Typically, these complex systems in conjunction with their aquatic environment pose a fabulous challenge to theoretical description, simulation, and prediction. In this work, we propose a differential geometry based multiscale paradigm to model complex macromolecular systems, and to put macroscopic and microscopic descriptions on an equal footing. In our approach, the differential geometry theory of surfaces and geometric measure theory are employed as a natural means to couple the macroscopic continuum mechanical description of the aquatic environment with the microscopic discrete atom-istic description of the macromolecule. Multiscale free energy functionals, or multiscale action functionals are constructed as a unified framework to derive the governing equations for the dynamics of different scales and different descriptions. Two types of aqueous macromolecular complexes, ones that are near equilibrium and others that are far from equilibrium, are considered in our formulations. We show that generalized Navier–Stokes equations for the fluid dynamics, generalized Poisson equations or generalized Poisson–Boltzmann equations for electrostatic interactions, and Newton's equation for the molecular dynamics can be derived by the least action principle. These equations are coupled through the continuum-discrete interface whose dynamics is governed by potential driven geometric flows. Comparison is given to classical descriptions of the fluid and electrostatic interactions without geometric flow based micro-macro interfaces. The detailed balance of forces is emphasized in the present work. We further extend the proposed multiscale paradigm to micro-macro analysis of electrohydrodynamics, electrophoresis, fuel cells, and ion channels. We derive generalized Poisson–Nernst–Planck equations that

  2. Differential geometry based multiscale models.

    PubMed

    Wei, Guo-Wei

    2010-08-01

    Large chemical and biological systems such as fuel cells, ion channels, molecular motors, and viruses are of great importance to the scientific community and public health. Typically, these complex systems in conjunction with their aquatic environment pose a fabulous challenge to theoretical description, simulation, and prediction. In this work, we propose a differential geometry based multiscale paradigm to model complex macromolecular systems, and to put macroscopic and microscopic descriptions on an equal footing. In our approach, the differential geometry theory of surfaces and geometric measure theory are employed as a natural means to couple the macroscopic continuum mechanical description of the aquatic environment with the microscopic discrete atomistic description of the macromolecule. Multiscale free energy functionals, or multiscale action functionals are constructed as a unified framework to derive the governing equations for the dynamics of different scales and different descriptions. Two types of aqueous macromolecular complexes, ones that are near equilibrium and others that are far from equilibrium, are considered in our formulations. We show that generalized Navier-Stokes equations for the fluid dynamics, generalized Poisson equations or generalized Poisson-Boltzmann equations for electrostatic interactions, and Newton's equation for the molecular dynamics can be derived by the least action principle. These equations are coupled through the continuum-discrete interface whose dynamics is governed by potential driven geometric flows. Comparison is given to classical descriptions of the fluid and electrostatic interactions without geometric flow based micro-macro interfaces. The detailed balance of forces is emphasized in the present work. We further extend the proposed multiscale paradigm to micro-macro analysis of electrohydrodynamics, electrophoresis, fuel cells, and ion channels. We derive generalized Poisson-Nernst-Planck equations that are

  3. Differential geometry based multiscale models.

    PubMed

    Wei, Guo-Wei

    2010-08-01

    Large chemical and biological systems such as fuel cells, ion channels, molecular motors, and viruses are of great importance to the scientific community and public health. Typically, these complex systems in conjunction with their aquatic environment pose a fabulous challenge to theoretical description, simulation, and prediction. In this work, we propose a differential geometry based multiscale paradigm to model complex macromolecular systems, and to put macroscopic and microscopic descriptions on an equal footing. In our approach, the differential geometry theory of surfaces and geometric measure theory are employed as a natural means to couple the macroscopic continuum mechanical description of the aquatic environment with the microscopic discrete atomistic description of the macromolecule. Multiscale free energy functionals, or multiscale action functionals are constructed as a unified framework to derive the governing equations for the dynamics of different scales and different descriptions. Two types of aqueous macromolecular complexes, ones that are near equilibrium and others that are far from equilibrium, are considered in our formulations. We show that generalized Navier-Stokes equations for the fluid dynamics, generalized Poisson equations or generalized Poisson-Boltzmann equations for electrostatic interactions, and Newton's equation for the molecular dynamics can be derived by the least action principle. These equations are coupled through the continuum-discrete interface whose dynamics is governed by potential driven geometric flows. Comparison is given to classical descriptions of the fluid and electrostatic interactions without geometric flow based micro-macro interfaces. The detailed balance of forces is emphasized in the present work. We further extend the proposed multiscale paradigm to micro-macro analysis of electrohydrodynamics, electrophoresis, fuel cells, and ion channels. We derive generalized Poisson-Nernst-Planck equations that are

  4. Stringy differential geometry, beyond Riemann

    NASA Astrophysics Data System (ADS)

    Jeon, Imtak; Lee, Kanghoon; Park, Jeong-Hyuck

    2011-08-01

    While the fundamental object in Riemannian geometry is a metric, closed string theories call for us to put a two-form gauge field and a scalar dilaton on an equal footing with the metric. Here we propose a novel differential geometry that treats the three objects in a unified manner, manifests not only diffeomorphism and one-form gauge symmetry but also O(D,D) T-duality, and enables us to rewrite the known low energy effective action of them as a single term. Further, we develop a corresponding vielbein formalism and gauge the internal symmetry that is given by a direct product of two local Lorentz groups, SO(1,D-1)×SŌ(1,D-1). We comment that the notion of cosmological constant naturally changes.

  5. Differential Complexes in Continuum Mechanics

    NASA Astrophysics Data System (ADS)

    Angoshtari, Arzhang; Yavari, Arash

    2015-04-01

    We study some differential complexes in continuum mechanics that involve both symmetric and non-symmetric second-order tensors. In particular, we show that the tensorial analogue of the standard grad-curl-div complex can simultaneously describe the kinematics and the kinetics of motion of a continuum. The relation between this complex and the de Rham complex allows one to readily derive the necessary and sufficient conditions for the compatibility of displacement gradient and the existence of stress functions on non-contractible bodies.We also derive the local compatibility equations in terms of the Green deformation tensor for motions of 2D and 3D bodies, and shells in curved ambient spaces with constant curvatures.

  6. Wage differentials due to gender.

    PubMed

    Smith, N; Westergard-nielsen, N

    1988-10-01

    "In this paper, a longitudinal data set covering 5% of all Danish wage earners over a 9-year period is used to shed light on the observed wage differentials due to gender. A human capital model is used to isolate the effects of changes in experience, schooling and unemployment, together with other factors.... Despite the observation from macro statistics that women have had the highest observed increases in wage rates, the models show that this increase is mainly due to an improvement in their background characteristics and that men still receive a higher return to their characteristics. The main difference between genders appears to be that female workers do not, in general, get any return to their experience. The estimates also show negative effects on the wage rate of previous spells of unemployment." PMID:12282508

  7. Thyroglobulin in differentiated thyroid cancer.

    PubMed

    Evans, Carol; Tennant, Sarah; Perros, Petros

    2015-04-15

    Identification of differentiated thyroid cancer (DTC) is becoming increasingly common. Patients usually have an excellent prognosis. Most undergo total thyroidectomy, radioiodine ablation and treatment with suppressive doses of levothyroxine. Patients require long term follow-up which includes measurement of serum thyroglobulin (Tg). Interpretation of serum Tg requires knowledge of the concurrent thyroid stimulating hormone (TSH) concentration, as secretion is TSH dependant, and an awareness of the limitations of the methods used to measure it. These limitations include the heterogeneity of Tg in serum, the ability of assays to recognise forms of Tg secreted by a tumour, assay biases and not least the potential for interference in immunoassays for Tg from endogenous thyroglobulin antibodies (TgAbs) in patient serum. This review considers what the clinician wants to know and how Tg results can be interpreted in light of an awareness of assay limitations. PMID:25444737

  8. Differential spacecraft tracking by interferometry

    NASA Technical Reports Server (NTRS)

    Border, James S.; Folkner, William M.

    1990-01-01

    This study estimates measurement system errors for two space vehicles on the surface of Mars, and for two Mars orbiting spacecraft, which are being tracked by differential interferometry. In these examples, signals from all spacecraft lie within the same beamwidth of an earth-based radio antenna. The measurements of all spacecraft signals are made simultaneously; errors that scale with angular source separation or with temporal separation between measurement epochs are practically removed. It is shown that errors due to system thermal noise and to systematic effects within ground receiver electronics dominate, except for geometries when signals pass close to the sun, when solar plasma becomes the dominant error source. The instantaneous relative position of two orbiters may be measured to within ten meters, leading to 50-meter three-dimensional orbital accuracy.

  9. Transcriptional Regulation and Macrophage Differentiation.

    PubMed

    Hume, David A; Summers, Kim M; Rehli, Michael

    2016-06-01

    Monocytes and macrophages are professional phagocytes that occupy specific niches in every tissue of the body. Their survival, proliferation, and differentiation are controlled by signals from the macrophage colony-stimulating factor receptor (CSF-1R) and its two ligands, CSF-1 and interleukin-34. In this review, we address the developmental and transcriptional relationships between hematopoietic progenitor cells, blood monocytes, and tissue macrophages as well as the distinctions from dendritic cells. A huge repertoire of receptors allows monocytes, tissue-resident macrophages, or pathology-associated macrophages to adapt to specific microenvironments. These processes create a broad spectrum of macrophages with different functions and individual effector capacities. The production of large transcriptomic data sets in mouse, human, and other species provides new insights into the mechanisms that underlie macrophage functional plasticity. PMID:27337479

  10. Differential Photometry at 1612 MHz

    NASA Astrophysics Data System (ADS)

    Lewis, B. Murray

    2009-01-01

    The 1612 MHz light curves of high latitude OH/IR stars have been observed for several years with the Arecibo 305m telescope, to derive the light-travel time diameter of their shells from the phase difference between their red and blue shifted peaks, and to look for secular evolution of their masers. However, direct intensity measurements are always limited by the extent to which the telescope's characteristics can be removed. These, in Arecibo's case, are subject to changes in the weight distribution about the structure over time, to the functioning of the vertical tie-down system, which can be interrupted by thunder storms, and by temperature-related zenith angle effects during daytime observations. Nevertheless, all of these limitations are neutralized when the ratio of the two peaks is used as the observed parameter. This form of differential photometry often results in clean light curves, though the ratio may still be perturbed by RFI, by interstellar scintillation, and more predictably by noise. The increased sensitivity of this observing mode readily detects (1) any differential evolution of the two masers, as well as (2) highlighting changes in masing gain between the two peaks around the pulsation cycle, that in turn are indicative of the operation of partially rather than fully saturated masers. In many of our light-curves there are abrupt changes in the ratio of the peak intensities at a constant pulsation phase. These are interpreted as being due to the onset of dust formation at that phase of the pulsation cycle, with a consequent abrupt change in the reprocessing of the stellar SED, and hence to an abrupt change in the maser pump. This is a feature of the Gray, Howe & Lewis (MN 364, 783 (2005)) maser model. Examples of these effects will be shown.

  11. Chromatin plasticity as a differentiation index during muscle differentiation of C2C12 myoblasts.

    PubMed

    Watanabe, Tomonobu M; Higuchi, Sayaka; Kawauchi, Keiko; Tsukasaki, Yoshikazu; Ichimura, Taro; Fujita, Hideaki

    2012-02-24

    Skeletal muscle undergoes complicated differentiation steps that include cell-cycle arrest, cell fusion, and maturation, which are controlled through sequential expression of transcription factors. During muscle differentiation, remodeling of the epigenetic landscape is also known to take place on a large scale, determining cell fate. In an attempt to determine the extent of epigenetic remodeling during muscle differentiation, we characterized the plasticity of the chromatin structure using C2C12 myoblasts. Differentiation of C2C12 cells was induced by lowering the serum concentration after they had reached full confluence, resulting in the formation of multi-nucleated myotubes. Upon induction of differentiation, the nucleus size decreased whereas the aspect ratio increased, indicating the presence of force on the nucleus during differentiation. Movement of the nucleus was also suppressed when differentiation was induced, indicating that the plasticity of chromatin changed upon differentiation. To evaluate the histone dynamics during differentiation, FRAP experiment was performed, which showed an increase in the immobile fraction of histone proteins when differentiation was induced. To further evaluate the change in the histone dynamics during differentiation, FCS was performed, which showed a decrease in histone mobility on differentiation. We here show that the plasticity of chromatin decreases upon differentiation, which takes place in a stepwise manner, and that it can be used as an index for the differentiation stage during myogenesis using the state diagram developed with the parameters obtained in this study.

  12. Differential effects of lenalidomide during plasma cell differentiation

    PubMed Central

    Jourdan, Michel; Cren, Maïlys; Schafer, Peter; Robert, Nicolas; Duperray, Christophe; Vincent, Laure; Ceballos, Patrice; Cartron, Guillaume; Rossi, Jean-François; Moreaux, Jérôme; Chopra, Rajesh; Klein, Bernard

    2016-01-01

    Thalidomide, lenalidomide and pomalidomide have greatly improved the outcome of patients with multiple myeloma. However, their effects on plasma cells, the healthy counterpart of myeloma cells, are unknown. Here, we investigated lenalidomide effects on normal human plasma cell generation using an in vitro model. Lenalidomide inhibited the generation of pre-plasmablasts and early plasma cells, while it moderately affected plasmablast production. It also reduced the expression level of Ikaros, Aiolos, and IRF4 transcription factors, in plasmablasts and early plasma cells. This suggests that their differential sensitivity to lenalidomide is not due to a difference in Ikaros or Aiolos degradation. Lenalidomide also inhibited long-lived plasma cell generation, but did not impair their long-term survival once generated. This last observation is in agreement with the finding that lenalidomide treatment for 3-18 months did not affect the bone marrow healthy plasma cell count in allografted patients with multiple myeloma. Our findings should prompt to investigate whether lenalidomide resistance in patients with multiple myeloma could be associated with the emergence of malignant plasmablasts or long-lived plasma cells that are less sensitive to lenalidomide. PMID:27057635

  13. Phase jitter in a differential phase experiment.

    NASA Technical Reports Server (NTRS)

    Tanenbaum, B. S.; Connolly, D. J.; Austin, G. L.

    1973-01-01

    Austin (1971) had concluded that, because of the 'phase jitter,' the differential phase experiment is useful over a more limited height range than the differential absorption experiment. Several observations are presented to show that this conclusion is premature. It is pointed out that the logical basis of the differential absorption experiment also requires that the O- and X-mode echoes, at a given time, come from the same irregularities. Austin's calculations are believed to contain a systematic error above 80 km.

  14. Tight regulation of wingless-type signaling in the articular cartilage - subchondral bone biomechanical unit: transcriptomics in Frzb-knockout mice

    PubMed Central

    2012-01-01

    Introduction The aim of this research was to study molecular changes in the articular cartilage and subchondral bone of the tibial plateau from mice deficient in frizzled-related protein (Frzb) compared to wild-type mice by transcriptome analysis. Methods Gene-expression analysis of the articular cartilage and subchondral bone of three wild-type and three Frzb-/- mice was performed by microarray. Data from three wild-type and two Frzb-/- samples could be used for pathway analysis of differentially expressed genes and were explored with PANTHER, DAVID and GSEA bioinformatics tools. Activation of the wingless-type (WNT) pathway was analysed using Western blot. The effects of Frzb gain and loss of function on chondrogenesis and cell proliferation was examined using ATDC5 micro-masses and mouse ribcage chondrocytes. Results Extracellular matrix-associated integrin and cadherin pathways, as well as WNT pathway genes were up-regulated in Frzb-/- samples. Several WNT receptors, target genes and other antagonists were up-regulated, but no difference in active β-catenin was found. Analysis of ATDC5 cell micro-masses overexpressing FRZB indicated an up-regulation of aggrecan and Col2a1, and down-regulation of molecules related to damage and repair in cartilage, Col3a1 and Col5a1. Silencing of Frzb resulted in down-regulation of aggrecan and Col2a1. Pathways associated with cell cycle were down-regulated in this transcriptome analysis. Ribcage chondrocytes derived from Frzb-/- mice showed decreased proliferation compared to wild-type cells. Conclusions Our analysis provides evidence for tight regulation of WNT signalling, shifts in extracellular matrix components and effects on cell proliferation and differentiation in the articular cartilage - subchondral bone unit in Frzb-/- mice. These data further support an important role for FRZB in joint homeostasis and highlight the complex biology of WNT signaling in the joint. PMID:22264237

  15. An edge preserving differential image coding scheme

    NASA Technical Reports Server (NTRS)

    Rost, Martin C.; Sayood, Khalid

    1992-01-01

    Differential encoding techniques are fast and easy to implement. However, a major problem with the use of differential encoding for images is the rapid edge degradation encountered when using such systems. This makes differential encoding techniques of limited utility, especially when coding medical or scientific images, where edge preservation is of utmost importance. A simple, easy to implement differential image coding system with excellent edge preservation properties is presented. The coding system can be used over variable rate channels, which makes it especially attractive for use in the packet network environment.

  16. Nrf2 promotes neuronal cell differentiation

    PubMed Central

    Zhao, Fei; Wu, Tongde; Lau, Alexandria; Jiang, Tao; Huang, Zheping; Wang, Xiao-Jun; Chen, Weimin; Wong, Pak Kin; Zhang, Donna D.

    2009-01-01

    The transcription factor Nrf2 has emerged as a master regulator for the endogenous antioxidant response, which is critical in defending cells against environmental insults and in maintaining intracellular redox balance. However, whether Nrf2 has any role in neuronal cell differentiation is largely unknown. In this report, we have examined the effects of Nrf2 on cell differentiation using a neuroblastoma cell line, SH-SY5Y. Retinoic acid (RA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), two well-studied inducers for neuronal differentiation, are able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 (NQO1) in a dose- and time- dependent manner. RA-induced Nrf2 up-regulation is accompanied by neurite outgrowth and an induction of two neuronal differentiation markers, neurofilament-M (NF-M) and microtubule-associated protein 2 (MAP-2). Overexpression of Nrf2 in SH-SY5Y cells promotes neuronal differentiation whereas inhibition of endogenous Nrf2 expression inhibited neuronal differentiation. More remarkably, the positive role of Nrf2 in neuronal differentiation was verified ex vivo in primary neuron culture. Primary neurons isolated from Nrf2-null mice showed a retarded progress in differentiation, compared to that from wild-type mice. Collectively, our data demonstrate a novel role for Nrf2 in promoting neuronal cell differentiation, which will open new perspectives for therapeutic uses of Nrf2 activators in patients with neurodegenerative diseases. PMID:19573594

  17. An Introduction to Lagrangian Differential Calculus.

    ERIC Educational Resources Information Center

    Schremmer, Francesca; Schremmer, Alain

    1990-01-01

    Illustrates how Lagrange's approach applies to the differential calculus of polynomial functions when approximations are obtained. Discusses how to obtain polynomial approximations in other cases. (YP)

  18. Minimal model for stem-cell differentiation

    NASA Astrophysics Data System (ADS)

    Goto, Yusuke; Kaneko, Kunihiko

    2013-09-01

    To explain the differentiation of stem cells in terms of dynamical systems theory, models of interacting cells with intracellular protein expression dynamics are analyzed and simulated. Simulations were carried out for all possible protein expression networks consisting of two genes under cell-cell interactions mediated by the diffusion of a protein. Networks that show cell differentiation are extracted and two forms of symmetric differentiation based on Turing's mechanism and asymmetric differentiation are identified. In the latter network, the intracellular protein levels show oscillatory dynamics at a single-cell level, while cell-to-cell synchronicity of the oscillation is lost with an increase in the number of cells. Differentiation to a fixed-point-type behavior follows with a further increase in the number of cells. The cell type with oscillatory dynamics corresponds to a stem cell that can both proliferate and differentiate, while the latter fixed-point type only proliferates. This differentiation is analyzed as a saddle-node bifurcation on an invariant circle, while the number ratio of each cell type is shown to be robust against perturbations due to self-consistent determination of the effective bifurcation parameter as a result of the cell-cell interaction. Complex cell differentiation is designed by combing these simple two-gene networks. The generality of the present differentiation mechanism, as well as its biological relevance, is discussed.

  19. An edge preserving differential image coding scheme

    NASA Technical Reports Server (NTRS)

    Rost, Martin C.; Sayood, Khalid

    1991-01-01

    Differential encoding techniques are fast and easy to implement. However, a major problem with the use of differential encoding for images is the rapid edge degradation encountered when using such systems. This makes differential encoding techniques of limited utility especially when coding medical or scientific images, where edge preservation is of utmost importance. We present a simple, easy to implement differential image coding system with excellent edge preservation properties. The coding system can be used over variable rate channels which makes it especially attractive for use in the packet network environment.

  20. Early Earth differentiation [rapid communication

    NASA Astrophysics Data System (ADS)

    Walter, Michael J.; Trønnes, Reidar G.

    2004-09-01

    The birth and infancy of Earth was a time of profound differentiation involving massive internal reorganization into core, mantle and proto-crust, all within a few hundred million years of solar system formation ( t0). Physical and isotopic evidence indicate that the formation of iron-rich cores generally occurred very early in planetesimals, the building blocks of proto-Earth, within about 3 million years of t0. The final stages of terrestrial planetary accretion involved violent and tremendously energetic giant impacts among core-segregated Mercury- to Mars-sized objects and planetary embryos. As a consequence of impact heating, the early Earth was at times partially or wholly molten, increasing the likelihood for high-pressure and high-temperature equilibration among core- and mantle-forming materials. The Earth's silicate mantle harmoniously possesses abundance levels of the siderophile elements Ni and Co that can be reconciled by equilibration between iron alloy and silicate at conditions comparable to those expected for a deep magma ocean. Solidification of a deep magma ocean possibly involved crystal-melt segregation at high pressures, but subsequent convective stirring of the mantle could have largely erased nascent layering. However, primitive upper mantle rocks apparently have some nonchondritic major and trace element refractory lithophile element ratios that can be plausibly linked to early mantle differentiation of ultra-high-pressure mantle phases. The geochemical effects of crystal fractionation in a deep magma ocean are partly constrained by high-pressure experimentation. Comparison between compositional models for the primitive convecting mantle and bulk silicate Earth generally allows, and possibly favors, 10-15% total fractionation of a deep mantle assemblage comprised predominantly of Mg-perovskite and with minor but geochemically important amounts of Ca-perovskite and ferropericlase. Long-term isolation of such a crystal pile is generally

  1. Molecular differentiation of bovine sarcocysts.

    PubMed

    Akhlaghi, Majedeh; Razavi, Mostafa; Hosseini, Arsalan

    2016-07-01

    Cattle are common intermediate hosts of Sarcocystis, and the prevalence in adult bovine muscle is close to 100 % in most regions of the world. Three Sarcocystis spp. are known to infect cattle as intermediate hosts, namely, S. cruzi, S. hirsuta, and S. hominis. The aim of the present study was the molecular identification and differentiation of these three species, Neospora caninum and Besnoitia by PCR and RFLP methods. Tissue samples were obtained from diaphragmatic muscle of 101 cattle slaughtered in Shiraz, Fars Province, Iran, for both smear preparation and DNA extraction. The samples were digested by Pepsin, washed three times with PBS solution before taking smears, fixed in absolute methanol and stained with 10 % Giemsa. The slides were examined microscopically for Sarcocystis bradyzoites and DNA was extracted from 100 mg of Sarcocystis-infected meat samples. Since the primers also bind to 18S rRNA gene of some tissue cyst-forming coccidian protozoa, DNA was also extracted from 100 μl of tachyzoite-containing suspension of N. caninum and Besnoitia isolated from goat to compare RFLP pattern. Polymerase chain reaction (PCR) was performed on DNA of samples which were microscopically positive for Sarcocystis. Five restriction enzymes Dra1, EcoRV, RsaI, AvaI, and SspI were used for RFLP and DNA of one sample from protozoa was sequenced. Based on the RFLP results, 87 (98.9 %) DNA samples were cut with DraI, indicating infection by S. cruzi. One sample (1.1 %) of PCR products of infected samples was cut only with EcoRV which showed S. hominis infection. Forty-eight samples (53.3 %) of PCR products were cut with both DraI, EcoRV, or with DraI, EcoRV, and RsaI while none of them was cut with SspI, which shows the mixed infection of both S. cruzi and S. hominis and no infection with S. hirsuta. It seems by utilizing these restriction enzymes, RLFP could be a suitable method not only for identification of Sarcocystis species but also for differentiating them

  2. NASA's Global Differential GPS System

    NASA Astrophysics Data System (ADS)

    Bar-Sever, Y.; Muellerschoen, R.

    2003-04-01

    The NASA Global Differential GPS (GDGPS) system provides an unparalleled combination of real time positioning accuracy and availability. Developed and operated by the Jet Propulsion Laboratory (JPL) for NASA’s terrestrial, airborne, and spaceborne applications, the GDGPS system processes real time GPS data from a global network of more than 40 dual frequency GPS ground sites. It is the only network providing global, multiply-redundant, real time coverage of all GPS satellites, all the time. The system has demonstrated real time positioning accuracy of 10 cm horizontally, and 20 cm vertically for users anywhere in the world, on the ground and in the air. Real time orbit determination of low Earth satellites carrying precise GPS receivers was demonstrated to achieve accuracy of 10 30 cm 3D RMS (depending primarily on altitude). A track record of 99.99% availability extends from January 2000 to the present. We will describe the unique Internet-based architecture of the system, and the concept of reliability through redundancy, and discuss the capability of system to enhance many science and civil applications, as well as the potential of the system for GPS integrity monitoring and for GPS enhancements.

  3. Differentiating tissue by fluorescence spectroscopy

    NASA Astrophysics Data System (ADS)

    Woessner, Stefan; Huen, Julien; Malthan, Dirk

    2004-03-01

    A common problem in several surgical applications is the lack of navigational information. Most often, the only source of information about the location of crucial structures, in relation to the surgical instrument, is the visible and tactile sensory input of the surgeon. In some cases, this leads to time-consuming procedures and a high risk for the patient. Therefore, we developed a spectroscopic sensor system for automatic differentiation between several tissue types. For example in milling processes, a sensor that is able to detect bone in contrast to nerve or vein tissue can be used to control the milling process. We showed exemplarily for the cochlea implant, a typical ENT-surgery, that with the help of our sensor system, the milling of bone can be accelerated without increasing the risk for the patient. It is also possible to use this type of sensor system in the area of medical robotics in soft-tissue applications. With real-time information, a continuous registration can take place, in contrast to a registration that is done using static preoperatively acquired images. We showed that our sensor system can be used to dynamically update the location of the patient in relation to CT or MR-images. In conclusion, we have been able to show that well-known spectroscopy sensors can be used to open new possibilities in medical treatment with and without the use of robotics.

  4. Differential Roles of PML Isoforms

    PubMed Central

    Nisole, Sébastien; Maroui, Mohamed Ali; Mascle, Xavier H.; Aubry, Muriel; Chelbi-Alix, Mounira K.

    2013-01-01

    The tumor suppressor promyelocytic leukemia (PML) protein is fused to the retinoic acid receptor alpha in patients suffering from acute promyelocytic leukemia (APL). Treatment of APL patients with arsenic trioxide (As2O3) reverses the disease phenotype by a process involving the degradation of the fusion protein via its PML moiety. Several PML isoforms are generated from a single PML gene by alternative splicing. They share the same N-terminal region containing the RBCC/tripartite motif but differ in their C-terminal sequences. Recent studies of all the PML isoforms reveal the specific functions of each. Here, we review the nomenclature and structural organization of the PML isoforms in order to clarify the various designations and classifications found in different databases. The functions of the PML isoforms and their differential roles in antiviral defense also are reviewed. Finally, the key players involved in the degradation of the PML isoforms in response to As2O3 or other inducers are discussed. PMID:23734343

  5. Existence of anti-periodic (differentiable) mild solutions to semilinear differential equations with nondense domain.

    PubMed

    Liu, Jinghuai; Zhang, Litao

    2016-01-01

    In this paper, we investigate the existence of anti-periodic (or anti-periodic differentiable) mild solutions to the semilinear differential equation [Formula: see text] with nondense domain. Furthermore, an example is given to illustrate our results. PMID:27350933

  6. A Unified Introduction to Ordinary Differential Equations

    ERIC Educational Resources Information Center

    Lutzer, Carl V.

    2006-01-01

    This article describes how a presentation from the point of view of differential operators can be used to (partially) unify the myriad techniques in an introductory course in ordinary differential equations by providing students with a powerful, flexible paradigm that extends into (or from) linear algebra. (Contains 1 footnote.)

  7. Detecting Differential Person Functioning in Emotional Intelligence

    ERIC Educational Resources Information Center

    Alsmadi, Yahia M.; Alsmadi, Abdalla A.

    2009-01-01

    Differential Item Functioning (DIF) is a widely used term in test development literature. It is very important to analyze test's data for DIF because It is a serious threat to validity. If the same data matrix was transposed, similar analysis can be carried for Differential Person Functioning (DPF). The purpose of this paper is to introduce and…

  8. Organizational Differentiation of Students and Educational Opportunity

    ERIC Educational Resources Information Center

    Sorensen, Aage Bottger

    1970-01-01

    An attempt is made to specify the crucial dimensions of organizational differentiation. This conceptual framework is then used in the formulation of a set of mechanisms that may account for a relationship between organizational differentiation and student behavior. (Author/JB)

  9. Differentiation and the Twice-Exceptional Student

    ERIC Educational Resources Information Center

    Franklin-Rohr, Cheryl

    2012-01-01

    Tier 1, the first level of instruction in the RtI (Response to Intervention) framework, is designed to meet the needs of 80% of students within the regular classroom. The only way to accomplish this goal is to use differentiation. Differentiation is not a singular process; it is rather a complicated process of adapting instructional strategies so…

  10. Leading and Managing a Differentiated Classroom

    ERIC Educational Resources Information Center

    Imbeau, Marcia B.; Tomlinson, Carol Ann

    2010-01-01

    While most books on classroom management focus on keeping kids in their seats and giving good directions, here is a breakthrough guide that explains how to lead a class that is differentiated to individual students' needs. The top authority on differentiated instruction, Carol Ann Tomlinson, teams up with educator and consultant Marcia B. Imbeau…

  11. Differentiating Instruction Using a Matrix Plan.

    ERIC Educational Resources Information Center

    Distad, Linda; Heacox, Diane

    2000-01-01

    Describes the Matrix Plan that is a planning grid with operational verbs related to Bloom's taxonomy and acts as a means for assisting teachers in differentiating instruction in the regular classroom. Explores a case where pre-service teachers utilized the Matrix Plan in order to help them learn about differential instruction. (CMK)

  12. Siblings' Differential Treatment in Mexican American Families

    ERIC Educational Resources Information Center

    McHale, Susan M.; Updegraff, Kimberly A.; Shanahan, Lilly; Crouter, Ann C.; Killoren, Sarah E.

    2005-01-01

    We investigated the patterns and correlates of parents differential treatment of adolescent siblings in 246 two-parent Mexican American families. In home interviews, siblings rated 7 domains of differential treatment (e.g., privileges, chores, warmth) as well as their adjustment and perceptions of parental acceptance and fairness, and both parents…

  13. School Leadership Actions to Support Differentiated Instruction

    ERIC Educational Resources Information Center

    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…

  14. New Electronic Technologies for Facilitating Differentiated Instruction

    ERIC Educational Resources Information Center

    Scalise, Kathleen

    2009-01-01

    With electronic technologies, differentiated instruction has the same meaning as in traditional instruction, but different tools are available for teachers to help students learn. Electronic technologies for differentiated instruction can add powerful new types of media inclusion, levels of interactivity, and response actions. This rapidly…

  15. Pleiotrophin antagonizes Brd2 during neuronal differentiation.

    PubMed

    Garcia-Gutierrez, Pablo; Juarez-Vicente, Francisco; Wolgemuth, Debra J; Garcia-Dominguez, Mario

    2014-06-01

    Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptn-mediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptn-mediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system.

  16. Lesson Plan Design for Facilitating Differentiated Instruction

    ERIC Educational Resources Information Center

    Baker, Pamela Hudson; Fleming, Louise Conn

    2005-01-01

    This study examines the role of lesson plan design in helping teacher candidates to meet diverse learning needs. The authors studied student teachers who had been taught to use a differential lesson plan to see if they were differentiating in their planning, assessment, and instruction. They concluded that, indeed, lesson plan design does…

  17. Differentiating Instruction To Teach All Learners.

    ERIC Educational Resources Information Center

    Brimfield, Renee; Masci, Frank; DeFiore, Denise

    2002-01-01

    Discusses differentiation in terms of the instructional program, school organization, staff development, and extensions beyond the classroom. Suggests learning activities with differing levels of cognitive challenge as vehicles for differentiated classrooms. Focuses curriculum on global citizenship and themes of identity, connections,…

  18. Lie algebras and linear differential equations.

    NASA Technical Reports Server (NTRS)

    Brockett, R. W.; Rahimi, A.

    1972-01-01

    Certain symmetry properties possessed by the solutions of linear differential equations are examined. For this purpose, some basic ideas from the theory of finite dimensional linear systems are used together with the work of Wei and Norman on the use of Lie algebraic methods in differential equation theory.

  19. Perceptions about Implementation of Differentiated Instruction

    ERIC Educational Resources Information Center

    Robinson, Lora; Maldonado, Nancy; Whaley, Jerita

    2014-01-01

    The absence of differentiated instruction in many classrooms stifles success for students who do not learn the same way as their peers. Providing teachers with the knowledge and tools to differentiate in their classrooms may increase test scores and help low achieving students find success, while expanding the learning growth of gifted and…

  20. Differential geometric methods in system theory.

    NASA Technical Reports Server (NTRS)

    Brockett, R. W.

    1971-01-01

    Discussion of certain problems in system theory which have been or might be solved using some basic concepts from differential geometry. The problems considered involve differential equations, controllability, optimal control, qualitative behavior, stochastic processes, and bilinear systems. The main goal is to extend the essentials of linear theory to some nonlinear classes of problems.

  1. Topologies for neutral functional differential equations.

    NASA Technical Reports Server (NTRS)

    Melvin, W. R.

    1973-01-01

    Bounded topologies are considered for functional differential equations of the neutral type in which present dynamics of the system are influenced by its past behavior. A special bounded topology is generated on a collection of absolutely continuous functions with essentially bounded derivatives, and an application to a class of nonlinear neutral functional differential equations due to Driver (1965) is presented.

  2. Solving Differential Equations Using Modified Picard Iteration

    ERIC Educational Resources Information Center

    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…

  3. Broadening the View of Differentiated Instruction

    ERIC Educational Resources Information Center

    Parsons, Seth A.; Dodman, Stephanie L.; Burrowbridge, Sarah Cohen

    2013-01-01

    Students in today's classrooms vary greatly in background, cultures, language proficiency, educational skills, and interests. To best meet students' diverse needs, teachers must differentiate their instruction. The authors argue that the current differentiation conversation focuses almost exclusively on lesson planning, but instead…

  4. Differentiating Science Instruction: Secondary Science Teachers' Practices

    ERIC Educational Resources Information Center

    Maeng, Jennifer L.; Bell, Randy L.

    2015-01-01

    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)…

  5. Product and Quotient Rules from Logarithmic Differentiation

    ERIC Educational Resources Information Center

    Chen, Zhibo

    2012-01-01

    A new application of logarithmic differentiation is presented, which provides an alternative elegant proof of two basic rules of differentiation: the product rule and the quotient rule. The proof can intrigue students, help promote their critical thinking and rigorous reasoning and deepen their understanding of previously encountered concepts. The…

  6. Multiple bit differential detection of offset QPSK

    NASA Technical Reports Server (NTRS)

    Simon, M.

    2003-01-01

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

  7. Nuclear Mechanics and Stem Cell Differentiation.

    PubMed

    Mao, Xinjian; Gavara, Nuria; Song, Guanbin

    2015-12-01

    Stem cells are characterized by their self-renewal and multi-lineage differentiation potential. Stem cell differentiation is a prerequisite for the application of stem cells in regenerative medicine and clinical therapy. In addition to chemical stimulation, mechanical cues play a significant role in regulating stem cell differentiation. The integrity of mechanical sensors is necessary for the ability of cells to respond to mechanical signals. The nucleus, the largest and stiffest cellular organelle, interacts with the cytoskeleton as a key mediator of cell mechanics. Nuclear mechanics are involved in the complicated interactions of lamins, chromatin and nucleoskeleton-related proteins. Thus, stem cell differentiation is intimately associated with nuclear mechanics due to its indispensable role in mechanotransduction and mechanical response. This paper reviews several main contributions of nuclear mechanics, highlights the hallmarks of the nuclear mechanics of stem cells, and provides insight into the relationship between nuclear mechanics and stem cell differentiation, which may guide clinical applications in the future.

  8. Demonstration of differential backscatter absorption gas imaging.

    PubMed

    Powers, P E; Kulp, T J; Kennedy, R

    2000-03-20

    Backscatter absorption gas imaging (BAGI) is a technique that uses infrared active imaging to generate real-time video imagery of gas plumes. We describe a method that employs imaging at two wavelengths (absorbed and not absorbed by the gas to be detected) to allow wavelength-differential BAGI. From the frames collected at each wavelength, an absorbance image is created that displays the differential absorbance of the atmosphere between the imager and the backscatter surface. This is analogous to a two-dimensional topographic differential absorption lidar or differential optical absorption spectroscopy measurement. Gas plumes are displayed, but the topographic scene image is removed. This allows a more effective display of the plume image, thus ensuring detection under a wide variety of conditions. The instrument used to generate differential BAGI is described. Data generated by the instrument are presented and analyzed to estimate sensitivity. PMID:18338030

  9. Basic models for differential inhibition of enzymes.

    PubMed

    Cappiello, Mario; Moschini, Roberta; Balestri, Francesco; Mura, Umberto; Del-Corso, Antonella

    2014-03-14

    The possible preferential action exerted by an inhibitor on the transformation of one of two agonist substrates catalyzed by the same enzyme has recently been reported in studies on aldose reductase inhibition. This event was defined as "intra-site differential inhibition" and the molecules able to exert this action as "differential inhibitors". This work presents some basic kinetic models describing differential inhibition. Using a simple analytic approach, the results show that differential inhibition can occur through either competitive or mixed type inhibition in which the inhibitor prevalently targets the free enzyme. The results may help in selecting molecules whose differential inhibitory action could be advantageous in controlling the activity of enzymes acting on more than one substrate.

  10. Siblings’ Differential Treatment in Mexican American Families

    PubMed Central

    McHale, Susan M.; Updegraff, Kimberly A.; Shanahan, Lilly; Crouter, Ann C.; Killoren, Sarah E.

    2008-01-01

    We investigated the patterns and correlates of parents’ differential treatment of adolescent siblings in 246 two-parent Mexican American families. In home interviews, siblings rated 7 domains of differential treatment (e.g., privileges, chores, warmth) as well as their adjustment and perceptions of parental acceptance and fairness, and both parents and adolescents reported on cultural dynamics. More gender-typed patterns of differential treatment were evident when parents were more oriented to Mexican than Anglo culture. The links between differential treatment and youth reports of adjustment, parental acceptance, and parental fairness were moderated by adolescents’ familism values, particularly for older siblings: Differential treatment was linked more strongly to adjustment and parent-youth relationship problems when youth reported lower levels of familism. PMID:18414595

  11. [Differential therapy with calcium antagonists].

    PubMed

    Scholze, Jürgen E

    2003-12-01

    EFFICACY OF CALCIUM ANTAGONISTS: Calcium-channel blockers (CCBs) have long been recognized as potent agents for hypertensive therapy, with substantial blood pressure reduction in all age groups and races. CCBs improve endothelial function, may positively influence atherosclerosis in carotid arteries, reduce left ventricular hypertrophy, and hypertrophy of the resistance vessels, and improve arterial compliance. They do not adversely affect lipids and serum glucose. USE IN PRACTICE: CCBs are also a heterogenous class of drugs composed of the phenylalkylamine verapamil, the benzothiazepine diltiazem, and the large group of dihydropyridines (DHPs) with the prototype nifedipine, and an increasing number of newer agents (e. g. nitrendipine, nisoldipine, amlodipine, felodipine, lacidipine and lercanidipine). DHPs are primarily vasodilators, lowering blood pressure by decreasing peripheral vascular resistance at the level of the small arterioles which can be followed by an autonomic counterregulation especially in drugs with a rapid onset of action. This is markedly reduced or abolished in the treatment with the modern long acting DHPs and is also not the case in the treatment with non-DHPs. Prospective randomized controlled outcome studies demonstrated a significant reduction in stroke in elderly patients with isolated systolic hypertension compared with placebo (Syst-Eur [Syst-China]), and no significant differences in cardiovascular mortality and combined morbidity compared with diuretics, beta blockers or ACE-Inhibitors (STOP-2, INSIGHT, NORDIL, ALLHAT, INVEST). To normalize the blood pressure it is mostly necessary to combine antihypertensive drugs. Here are CCBs ideal partners for a therapy with ACE-inhibitors, AT1 antagonists or beta blockers (DHP) and diuretics (verapamil). With respect to the antihypertensive differential therapy the author recommends CCBs based on studies with the evidence grade 1-3; especially for elderly hypertensives (with isolated systolic

  12. Differential dopamine function in fibromyalgia.

    PubMed

    Albrecht, Daniel S; MacKie, Palmer J; Kareken, David A; Hutchins, Gary D; Chumin, Evgeny J; Christian, Bradley T; Yoder, Karmen K

    2016-09-01

    Approximately 30 % of Americans suffer from chronic pain disorders, such as fibromyalgia (FM), which can cause debilitating pain. Many pain-killing drugs prescribed for chronic pain disorders are highly addictive, have limited clinical efficacy, and do not treat the cognitive symptoms reported by many patients. The neurobiological substrates of chronic pain are largely unknown, but evidence points to altered dopaminergic transmission in aberrant pain perception. We sought to characterize the dopamine (DA) system in individuals with FM. Positron emission tomography (PET) with [(18)F]fallypride (FAL) was used to assess changes in DA during a working memory challenge relative to a baseline task, and to test for associations between baseline D2/D3 availability and experimental pain measures. Twelve female subjects with FM and 11 female controls completed study procedures. Subjects received one FAL PET scan while performing a "2-back" task, and one while performing a "0-back" (attentional control, "baseline") task. FM subjects had lower baseline FAL binding potential (BP) in several cortical regions relative to controls, including anterior cingulate cortex. In FM subjects, self-reported spontaneous pain negatively correlated with FAL BP in the left orbitofrontal cortex and parahippocampal gyrus. Baseline BP was significantly negatively correlated with experimental pain sensitivity and tolerance in both FM and CON subjects, although spatial patterns of these associations differed between groups. The data suggest that abnormal DA function may be associated with differential processing of pain perception in FM. Further studies are needed to explore the functional significance of DA in nociception and cognitive processing in chronic pain.

  13. [Evolution of differential chromosome banding].

    PubMed

    Rodionov, A V

    1999-03-01

    Specific chromosome banding patterns in different eukaryotic taxons are reviewed. In all eukaryotes, chromosomes are composed of alternating bands, each differing from the adjacent material by the molecular composition and structural characteristics. In minute chromosomes of fungi and Protozoa, these bands are represented by kinetochores (Kt- (Cd-)bands), nucleolus organizers (N-bands), and telomeres as well as the euchromatin. In genomes of most fungi and protists, long clusters of tandem repeats and, consequently, C-bands were not revealed but they are likely to be found out in species with chromosomes visible under a light microscope, which are several tens of million bp in size. Chromosomes of Metazoa are usually larger. Even in Cnidaria, they contain C-bands, which are replicated late in the S phase. In Deuterostomia, chromosome euchromatin regions differ by replication time: bands replicating at the first half of the S phase alternate with bands replicating at the second half of the S phase. Longitudinal differentiation in the replication pattern of euchromatic regions is observed in all classes of Vertebrata beginning with the bony fish although the time when it developed in Deuterostomia is unknown. Apparently, the evolution of early and late replicating subdomains in Vertebrata euchromatin promoted fast accumulation of differences in the molecular composition of nucleoproteid complexes characteristic of early and late replicating bands. As a result, the more contrasting G/R and Q-banding patterns of chromosomes developed especially in Eutheria. The evolution of Protostomia and Plantae followed another path. An increase in chromosome size was not accompanied by the appearance of wide RBE and RBL euchromatin bands. The G/R-like banding within the interstitial chromosome regions observed in some representatives of Invertebrates and higher plants arose independently in different phylogenetic lineages. This banding pattern seems to be closer to that of C

  14. Chromatin plasticity as a differentiation index during muscle differentiation of C2C12 myoblasts

    SciTech Connect

    Watanabe, Tomonobu M.; Higuchi, Sayaka; Kawauchi, Keiko; Tsukasaki, Yoshikazu; Ichimura, Taro; Fujita, Hideaki

    2012-02-24

    Highlights: Black-Right-Pointing-Pointer Change in the epigenetic landscape during myogenesis was optically investigated. Black-Right-Pointing-Pointer Mobility of nuclear proteins was used to state the epigenetic status of the cell. Black-Right-Pointing-Pointer Mobility of nuclear proteins decreased as myogenesis progressed in C2C12. Black-Right-Pointing-Pointer Differentiation state diagram was developed using parameters obtained. -- Abstract: Skeletal muscle undergoes complicated differentiation steps that include cell-cycle arrest, cell fusion, and maturation, which are controlled through sequential expression of transcription factors. During muscle differentiation, remodeling of the epigenetic landscape is also known to take place on a large scale, determining cell fate. In an attempt to determine the extent of epigenetic remodeling during muscle differentiation, we characterized the plasticity of the chromatin structure using C2C12 myoblasts. Differentiation of C2C12 cells was induced by lowering the serum concentration after they had reached full confluence, resulting in the formation of multi-nucleated myotubes. Upon induction of differentiation, the nucleus size decreased whereas the aspect ratio increased, indicating the presence of force on the nucleus during differentiation. Movement of the nucleus was also suppressed when differentiation was induced, indicating that the plasticity of chromatin changed upon differentiation. To evaluate the histone dynamics during differentiation, FRAP experiment was performed, which showed an increase in the immobile fraction of histone proteins when differentiation was induced. To further evaluate the change in the histone dynamics during differentiation, FCS was performed, which showed a decrease in histone mobility on differentiation. We here show that the plasticity of chromatin decreases upon differentiation, which takes place in a stepwise manner, and that it can be used as an index for the differentiation stage

  15. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba; Christopher J. Ziolkowski

    2004-06-30

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a simple sensor incorporated into the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD equipment. Imaging

  16. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba

    2003-10-01

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a simple sensor incorporated into the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD equipment. Imaging

  17. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba

    2003-04-01

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a thin film sensor conformal with the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is capacitively coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD

  18. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba

    2003-01-30

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a thin film sensor conformal with the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is capacitively coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD

  19. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba

    2002-08-30

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a thin film sensor conformal with the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is capacitively coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD

  20. DIFFERENTIAL SOIL IMPEDANCE OBSTACLE DETECTION

    SciTech Connect

    Maximillian J. Kieba

    2002-11-27

    This project develops a new and unique obstacle detection sensor for horizontal directional drilling (HDD) equipment. The development of this new technology will greatly improve the reliability and safety of natural gas HDD construction practices. This sensor utilizes a differential soil impedance measurement technique that will be sensitive to the presence of plastic and ceramic, as well as metallic obstacles. The use of HDD equipment has risen significantly in the gas industry because HDD provides a much more cost-effective and less disruptive method for gas pipe installation than older, trenching methods. However, there have been isolated strikes of underground utilities by HDD equipment, which may have been avoided if methods were available to detect other underground obstacles when using HDD systems. GTI advisors from the gas industry have ranked the value of solving the obstacle detection problem as the most important research and development project for GTI to pursue using Federal Energy Regulatory Commission (FERC) funds available through its industry partner, GRI. GTI proposes to develop a prototype down-hole sensor system that is simple and compact. The sensor utilizes an impedance measurement technique that is sensitive to the presence of metallic or nonmetallic objects in the proximity of the HDD head. The system will use a thin film sensor conformal with the drill head. The impedance of the soil will be measured with a low frequency signal injected through the drill head itself. A pair of bridge type impedance sensors, mounted orthogonal to one another, is capacitively coupled to the soil. Inclusions in the soil will cause changes to the sensor balance distinguishable from homogeneous soil. The sensor will provide range and direction data for obstacles near the HDD head. The goal is to provide a simple, robust system that provides the information required to avoid obstacles. This must be done within the size and ruggedness constraints of the HDD

  1. Compositional differentiation of Enceladus' plume

    NASA Astrophysics Data System (ADS)

    Khawaja, N.; Postberg, F.; Schmidt, J.

    2014-04-01

    The Cosmic Dust Analyser (CDA) on board the Cassini spacecraft sampled Enceladus' plume ice particles emanated directly from Enceladus' fractured south polar terrain (SPT), the so-called "Tiger Stripes", during two consecutive flybys (E17 and E18) in 2012. The spacecraft passed through the dense plume with a moderate velocity of ~7.5km/s, horizontally to the SPT with a closest approach (CA) at an altitude of ~75km almost directly over the south pole. In both flybys, spectra were recorded during a time interval of ~ ±3 minutes with respect to the closest approach achieving an average sampling rate of about 0.6 sec-1. We assume that the spacecraft passed through the plume during an interval of about ±60(sec) from the CA. Particles encountered before and after this period are predominately from the E-ring background in which Enceladus is embedded. Most CDA TOF-mass spectra are identified as one of three compositional types: (i) almost pure water (ii) organic rich and (iii) salt rich [2]. A Boxcar Analysis (BCA) is performed from a count database for compositional mapping of the plume along the space-craft trajectory. In BCA, counts of each spectrum type are integrated for a certain interval of time (box size). The integral of counts represents frequencies of compositional types in absolute abundances, which are converted later into proportions. This technique has been proven to be a suitable for inferring the compositional profiles from an earlier flyby (E5) [1]. The inferred compositional profiles show similar trends on E17 and E18. The abundances of different compositional types in the plume clearly differ from the Ering background and imply a compositional differentiation inside the plume. Following up the work of Schmidt et al, 2008 and Postberg et al, 2011 we can link different compositional types to different origins. The E17/E18 results are compared with the E5 flyby in 2008, which yielded the currently best compositional profile [2] but was executed at much

  2. Transcriptional control of spermatogonial maintenance and differentiation

    PubMed Central

    Song, Hye-Won; Wilkinson, Miles F.

    2014-01-01

    Spermatogenesis is a multistep process that generates millions of spermatozoa per day in mammals. A key to this process is the spermatogonial stem cell (SSC), which has the dual property of continually renewing and undergoing differentiation into a spermatogonial progenitor that expands and further differentiates. In this review, we will focus on how these proliferative and early differentiation steps in mammalian male germ cells are controlled by transcription factors. Most of the transcription factors that have so far been identified as promoting SSC self-renewal (BCL6B, BRACHYURY, ETV5, ID4, LHX1, and POU3F1) are upregulated by glial cell line-derived neurotrophic factor (GDNF). Since GDNF is crucial for promoting SSC self-renewal, this suggests that these transcription factors are responsible for coordinating the action of GDNF in SSCs. Other transcription factors that promote SSC self-renewal are expressed independently of GDNF (FOXO1, PLZF, POU5F1, and TAF4B) and thus may act in non-GDNF pathways to promote SSC cell growth or survival. Several transcription factors have been identified that promote spermatogonial differentiation (DMRT1, NGN3, SOHLH1, SOHLH2, SOX3, and STAT3); some of these may influence the decision of an SSC to commit to differentiate while others may promote later spermatogonial differentiation steps. Many of these transcription factors regulate each other and act on common targets, suggesting they integrate to form complex transcriptional networks in self-renewing and differentiating spermatogonia. PMID:24560784

  3. Dynamics of protein secretion during adipocyte differentiation.

    PubMed

    Ojima, Koichi; Oe, Mika; Nakajima, Ikuyo; Muroya, Susumu; Nishimura, Takanori

    2016-08-01

    The major functions of adipocytes include both lipid storage and the production of secretory factors. However, the type of proteins released from mouse 3T3-L1 cells during adipocyte differentiation remains poorly understood. We examined the dynamics of secreted proteins during adipocyte differentiation using mass spectrometry (MS) combined with an iTRAQ (®) labeling method that enables the simultaneous analysis of relative protein expression levels. A total of 215 proteins were identified and quantified from approximately 10 000 MS/MS spectra. Of these, approximately 38% were categorized as secreted proteins based on gene ontology classification. Adipokine secretion levels were increased with the progression of differentiation. By contrast, levels of fibril collagen components, such as subunits of type I and III collagens, were decreased during differentiation. Basement membrane components attained their peak levels at day 4 when small lipid droplets accumulated in differentiated 3T3-L1 cells. Simultaneously, peak levels of collagen microfibril components that comprise type V and VI collagen subunits were also observed. Our data demonstrated that extracellular matrix components were predominantly released during the early and middle stages of adipocyte differentiation, with a subsequent increase in the secretion of adipokines. This suggests that 3T3-L1 cells secrete adipokines after their ECM is constructed during adipocyte differentiation. PMID:27516960

  4. Neural differentiation and synaptogenesis in retinal development

    PubMed Central

    Fan, Wen-juan; Li, Xue; Yao, Huan-ling; Deng, Jie-xin; Liu, Hong-liang; Cui, Zhan-jun; Wang, Qiang; Wu, Ping; Deng, Jin-bo

    2016-01-01

    To investigate the pattern of neural differentiation and synaptogenesis in the mouse retina, immunolabeling, BrdU assay and transmission electron microscopy were used. We show that the neuroblastic cell layer is the germinal zone for neural differentiation and retinal lamination. Ganglion cells differentiated initially at embryonic day 13 (E13), and at E18 horizontal cells appeared in the neuroblastic cell layer. Neural stem cells in the outer neuroblastic cell layer differentiated into photoreceptor cells as early as postnatal day 0 (P0), and neural stem cells in the inner neuroblastic cell layer differentiated into bipolar cells at P7. Synapses in the retina were mainly located in the outer and inner plexiform layers. At P7, synaptophysin immunostaining appeared in presynaptic terminals in the outer and inner plexiform layers with button-like structures. After P14, presynaptic buttons were concentrated in outer and inner plexiform layers with strong staining. These data indicate that neural differentiation and synaptogenesis in the retina play important roles in the formation of retinal neural circuitry. Our study showed that the period before P14, especially between P0 and P14, represents a critical period during retinal development. Mouse eye opening occurs during that period, suggesting that cell differentiation and synaptic formation lead to the attainment of visual function. PMID:27073386

  5. Differential cross-sections with hard targets

    NASA Astrophysics Data System (ADS)

    Brun, J. L.; Pacheco, A. F.

    2005-09-01

    When the concept of scattering differential cross-section is introduced in classical mechanics textbooks, usually it is first supposed that the target is a fixed, hard sphere. In this paper we calculate the scattering differential cross-section in the case of the hard target being a fixed figure of revolution of any shape. When the target is a paraboloid of revolution, we find the well-known formula corresponding to Rutherford's scattering. In addition, we analyse the inverse problem, i.e. given a differential cross-section, what is the profile of the corresponding hard target?

  6. Mortality level, trends and differentials in Malawi.

    PubMed

    Palamuleni, M E

    1994-01-01

    "This article examines the levels, and trends and differentials in mortality in Malawi.... The study has shown that (i) the level of mortality is very high in Malawi; (ii) mortality has declined during the period under review; (iii) there was reduction in the rate of mortality decline in the seventies; and (iv) [there are] interesting differences in mortality in terms of rural-urban localities, regions and age-sex differentials. The observed levels, trends and differentials in mortality are however consistent with the level of social and economic development in the country."

  7. Psychological differentiation and the phenomenon of pain.

    PubMed

    Feldman, H R

    1984-01-01

    This article deals with a theory of psychological differentiation, research supporting this theory and identified indicators of differentiation, and studies that connect several of these indicators with the phenomenon of pain. Problems for investigation are posed concerning the relationships between differentiation indicators and pain threshold, pain tolerance, relief measures, attention to pain, control, and counterirritation An understanding of the kinds of variables affecting the pain experience can lead to a clearer perception and more astute evaluation of that experience and a more organized approach to the implementation of nursing care.

  8. Differential equations of time dependent order

    NASA Astrophysics Data System (ADS)

    Ludu, A.

    2016-10-01

    We introduce a special type of ordinary differential equations dx x/dtx = f (t, x) whose order of differentiation is a continuous variable depending on the dependent x or independent t variables. We show that such variable order of differentiation equations (VODE) can be solved as Volterra integral equations of second kind with singular integrable kernel. We find the conditions for existence and uniqueness of solutions of such VODE, and present some numeric solutions for particular cases exhibiting bifurcations and blow-up.

  9. Connecting Related Rates and Differential Equations

    ERIC Educational Resources Information Center

    Brandt, Keith

    2012-01-01

    This article points out a simple connection between related rates and differential equations. The connection can be used for in-class examples or homework exercises, and it is accessible to students who are familiar with separation of variables.

  10. Alternative splicing regulation and cell lineage differentiation.

    PubMed

    Liu, Huan; He, Ling; Tang, Liling

    2012-11-01

    The alternative splicing of precursor mRNA is an essential mechanism for protein diversity. It plays important biological roles, such as proliferation, differentiation and development of cells. Furthermore, alternative splicing participates in the pathogenesis of diseases, including cancer. Thus, in-depth understanding of splicing regulation is of great significance. Regulation of alternative splicing is an extraordinary complicated process in which several signal molecules are at work. Besides the cis-elements and trans-factors, several lines of evidences suggest that other molecules, structures or process also regulate splicing, such as RNA structures, transcription and transcription factors, chromatin and protein. Meanwhile, increasing body of evidence shows that alternative splicing correlated closely to stem cell lineage differentiation. It means that there is a fundamental role for splicing in controlling regulatory program required for cell lineage differentiation. This review systematically sums up the regulation of alternative splicing and summarizes the splicing events during cell lineage differentiation of stem cells.

  11. Differential Spectroscopic Imaging of Particulate Explosives Residue

    SciTech Connect

    Bernacki, Bruce E.; Ho, Nicolas

    2008-04-01

    We present experimental results showing transmission and reflection imaging of approximately 100 microgram quantities of particulate explosives residue using a commercial uncooled microbolometer infrared camera and CO2 laser differential wavelength illumination.

  12. WBC (White Blood Cell) Differential Count

    MedlinePlus

    ... Results of a differential are usually reported as absolute values of the five types of WBCs and/or ... a percent of the total number of WBCs. Absolute values are calculated by multiplying the total number of ...

  13. Differential radio astronomy of galactic objects

    NASA Technical Reports Server (NTRS)

    Backer, D. C.

    1980-01-01

    A differential astrometry technique is discussed. An improved proper motion and a parallax limit for pulsar 1929 + 10 is presented as well as a limit on the space velocity of the enigmatic object in SgrA.

  14. The epigenome in pluripotency and differentiation.

    PubMed

    Thiagarajan, Rathi D; Morey, Robert; Laurent, Louise C

    2014-02-01

    The ability to culture pluripotent stem cells and direct their differentiation into specific cell types in vitro provides a valuable experimental system for modeling pluripotency, development and cellular differentiation. High-throughput profiling of the transcriptomes and epigenomes of pluripotent stem cells and their differentiated derivatives has led to identification of patterns characteristic of each cell type, discovery of new regulatory features in the epigenome and early insights into the complexity of dynamic interactions among regulatory elements. This work has also revealed potential limitations of the use of pluripotent stem cells as in vitro models of developmental events, due to epigenetic variability among different pluripotent stem cell lines and epigenetic instability during derivation and culture, particularly at imprinted and X-inactivated loci. This review focuses on the two most well-studied epigenetic mechanisms, DNA methylation and histone modifications, within the context of pluripotency and differentiation. PMID:24579950

  15. Deregulated proliferation and differentiation in brain tumors

    PubMed Central

    Swartling, Fredrik J; Čančer, Matko; Frantz, Aaron; Weishaupt, Holger; Persson, Anders I

    2014-01-01

    Neurogenesis, the generation of new neurons, is deregulated in neural stem cell (NSC)- and progenitor-derived murine models of malignant medulloblastoma and glioma, the most common brain tumors of children and adults, respectively. Molecular characterization of human malignant brain tumors, and in particular brain tumor stem cells (BTSCs), has identified neurodevelopmental transcription factors, microRNAs, and epigenetic factors known to inhibit neuronal and glial differentiation. We are starting to understand how these factors are regulated by the major oncogenic drivers in malignant brain tumors. In this review, we will focus on the molecular switches that block normal neuronal differentiation and induce brain tumor formation. Genetic or pharmacological manipulation of these switches in BTSCs has been shown to restore the ability of tumor cells to differentiate. We will discuss potential brain tumor therapies that will promote differentiation in order to reduce treatment-resistance, suppress tumor growth, and prevent recurrence in patients. PMID:25416506

  16. [Differentiation between primary and neurotic sexual disorders].

    PubMed

    Leonhard, K

    1978-04-01

    The object of this paper is to show that there are different forms of sexual anomalies which permit of basic and therapeutic differentiation. Atavisms of responding have been observed to play an essential role in real perversions.

  17. Cell division, differentiation and dynamic clustering

    NASA Astrophysics Data System (ADS)

    Kaneko, Kunihiko; Yomo, Tetsuya

    1994-08-01

    A novel mechanism for cell differentiation is proposed, based on the dynamic clustering in a globally coupled nonlinear system. A simple model with metabolic reaction, active transport of chemicals from media, and cell division is found to show three successive stages with the growth of the number of cells; coherent growth, dynamic clustering, and fixed cell differentiation. At the last stage, disparity in activities, germ line segregation, somatic cell differentiation, and homeochaotic stability against external perturbation are found. Our results, providing a simple interpretation of the experiments of the preceding paper, imply that cell differentiation can occur without a spatial pattern. From dynamical systems viewpoint, the new concept of “open chaos” is proposed, as a novel and general scenario for systems with growing numbers of elements, also seen in economics and sociology.

  18. Specific Mindfulness Skills Differentially Predict Creative Performance.

    PubMed

    Baas, Matthijs; Nevicka, Barbara; Ten Velden, Femke S

    2014-05-23

    Past work has linked mindfulness to improved emotion regulation, interpersonal skills, and basic cognitive abilities, but is unclear about the relation between mindfulness and creativity. Studies examining effects of mindfulness on factors pertinent to creativity suggest a uniform and positive relation, whereas work on specific mindfulness skills suggests that mindfulness skills may differentially predict creativity. To test whether the relation between mindfulness and creativity is positive and uniform (the uniform hypothesis) or differentially depends on particular components of mindfulness (the differential hypothesis), we conducted four studies in which mindfulness skills were measured, extensively trained, or manipulated with a short, incidental meditation session. Results supported a differential relation between mindfulness and creativity: Only the ability to observe and attend to various stimuli consistently and positively predicted creativity. Results regarding other mindfulness skills were less consistent. Implications for theory and practice are discussed.

  19. Stochastic differential equation model to Prendiville processes

    SciTech Connect

    Granita; Bahar, Arifah

    2015-10-22

    The Prendiville process is another variation of the logistic model which assumes linearly decreasing population growth rate. It is a continuous time Markov chain (CTMC) taking integer values in the finite interval. The continuous time Markov chain can be approximated by stochastic differential equation (SDE). This paper discusses the stochastic differential equation of Prendiville process. The work started with the forward Kolmogorov equation in continuous time Markov chain of Prendiville process. Then it was formulated in the form of a central-difference approximation. The approximation was then used in Fokker-Planck equation in relation to the stochastic differential equation of the Prendiville process. The explicit solution of the Prendiville process was obtained from the stochastic differential equation. Therefore, the mean and variance function of the Prendiville process could be easily found from the explicit solution.

  20. Sex and Psychological Differentiation in Preschoolers

    ERIC Educational Resources Information Center

    Domash, Leanne; Balter, Lawrence

    1976-01-01

    Examined the relationship between selected maternal attitudes and the sex, sex role preference and level of psychological differentiation of the preschool child. Data indicate that extreme sex role typing works against learning. (GO)

  1. Superconductive microstrip exhibiting negative differential resistivity

    DOEpatents

    Huebener, R.P.; Gallus, D.E.

    1975-10-28

    A device capable of exhibiting negative differential electrical resistivity over a range of values of current and voltage is formed by vapor- depositing a thin layer of a material capable of exhibiting superconductivity on an insulating substrate, establishing electrical connections at opposite ends of the deposited strip, and cooling the alloy into its superconducting range. The device will exhibit negative differential resistivity when biased in the current- induced resistive state.

  2. Normal Forms for Nonautonomous Differential Equations

    NASA Astrophysics Data System (ADS)

    Siegmund, Stefan

    2002-01-01

    We extend Henry Poincarés normal form theory for autonomous differential equations x=f(x) to nonautonomous differential equations x=f(t, x). Poincarés nonresonance condition λj-∑ni=1 ℓiλi≠0 for eigenvalues is generalized to the new nonresonance condition λj∩∑ni=1 ℓiλi=∅ for spectral intervals.

  3. A class of neutral functional differential equations.

    NASA Technical Reports Server (NTRS)

    Melvin, W. R.

    1972-01-01

    Formulation and study of the initial value problem for neutral functional differential equations. The existence, uniqueness, and continuation of solutions to this problem are investigated, and an analysis is made of the dependence of the solutions on the initial conditions and parameters, resulting in the derivation of a continuous dependence theorem in which the fundamental mathematical principles underlying the continuous dependence problem for a very general system of nonlinear neutral functional differential equations are separated out.

  4. Extracting differential pair distribution functions using MIXSCAT

    SciTech Connect

    Wurden, Caroline; Page, Katharine; Llobet, Anna; White, Claire E.; Proffen, Thomas

    2010-08-27

    Differently weighted experimental scattering data have been used to extract partial or differential structure factors or pair distribution functions in studying many materials. However, this is not done routinely partly because of the lack of user-friendly software. This paper presents MIXSCAT, a new member of the DISCUS program package. MIXSCAT allows one to combine neutron and X-ray pair distribution functions and extract their respective differential functions.

  5. Low-voltage differentially-signaled modulators

    SciTech Connect

    Zortman, William A.; Lentine, Anthony L.; Hsia, Alexander H.; Watts, Michael R.

    2015-09-08

    Photonic modulators and methods of modulating an input optical signal are provided. A photonic modulator includes at least one modulator section and differential drive circuitry. The at least one modulator section includes a P-type layer and an N-type layer forming a PN junction in the modulator section. The differential drive circuitry is electrically coupled to the P-type layer and the N-type layer of the at least one modulator section.

  6. Differentiating Science Instruction: Secondary science teachers' practices

    NASA Astrophysics Data System (ADS)

    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.

  7. Jagged1 Instructs Macrophage Differentiation in Leprosy.

    PubMed

    Kibbie, Jon; Teles, Rosane M B; Wang, Zhiming; Hong, Patrick; Montoya, Dennis; Krutzik, Stephan; Lee, Seung; Kwon, Ohyun; Modlin, Robert L; Cruz, Daniel

    2016-08-01

    As circulating monocytes enter the site of disease, the local microenvironment instructs their differentiation into tissue macrophages (MΦ). To identify mechanisms that regulate MΦ differentiation, we studied human leprosy as a model, since M1-type antimicrobial MΦ predominate in lesions in the self-limited form, whereas M2-type phagocytic MΦ are characteristic of the lesions in the progressive form. Using a heterotypic co-culture model, we found that unstimulated endothelial cells (EC) trigger monocytes to become M2 MΦ. However, biochemical screens identified that IFN-γ and two families of small molecules activated EC to induce monocytes to differentiate into M1 MΦ. The gene expression profiles induced in these activated EC, when overlapped with the transcriptomes of human leprosy lesions, identified Jagged1 (JAG1) as a potential regulator of MΦ differentiation. JAG1 protein was preferentially expressed in the lesions from the self-limited form of leprosy, and localized to the vascular endothelium. The ability of activated EC to induce M1 MΦ was JAG1-dependent and the addition of JAG1 to quiescent EC facilitated monocyte differentiation into M1 MΦ with antimicrobial activity against M. leprae. Our findings indicate a potential role for the IFN-γ-JAG1 axis in instructing MΦ differentiation as part of the host defense response at the site of disease in human leprosy. PMID:27532668

  8. Jagged1 Instructs Macrophage Differentiation in Leprosy

    PubMed Central

    Teles, Rosane M. B.; Wang, Zhiming; Hong, Patrick; Montoya, Dennis; Krutzik, Stephan; Lee, Seung; Kwon, Ohyun; Modlin, Robert L.; Cruz, Daniel

    2016-01-01

    As circulating monocytes enter the site of disease, the local microenvironment instructs their differentiation into tissue macrophages (MΦ). To identify mechanisms that regulate MΦ differentiation, we studied human leprosy as a model, since M1-type antimicrobial MΦ predominate in lesions in the self-limited form, whereas M2-type phagocytic MΦ are characteristic of the lesions in the progressive form. Using a heterotypic co-culture model, we found that unstimulated endothelial cells (EC) trigger monocytes to become M2 MΦ. However, biochemical screens identified that IFN-γ and two families of small molecules activated EC to induce monocytes to differentiate into M1 MΦ. The gene expression profiles induced in these activated EC, when overlapped with the transcriptomes of human leprosy lesions, identified Jagged1 (JAG1) as a potential regulator of MΦ differentiation. JAG1 protein was preferentially expressed in the lesions from the self-limited form of leprosy, and localized to the vascular endothelium. The ability of activated EC to induce M1 MΦ was JAG1-dependent and the addition of JAG1 to quiescent EC facilitated monocyte differentiation into M1 MΦ with antimicrobial activity against M. leprae. Our findings indicate a potential role for the IFN-γ-JAG1 axis in instructing MΦ differentiation as part of the host defense response at the site of disease in human leprosy. PMID:27532668

  9. Inferring differentiation pathways from gene expression

    PubMed Central

    Costa, Ivan G.; Roepcke, Stefan; Hafemeister, Christoph; Schliep, Alexander

    2008-01-01

    Motivation: The regulation of proliferation and differentiation of embryonic and adult stem cells into mature cells is central to developmental biology. Gene expression measured in distinguishable developmental stages helps to elucidate underlying molecular processes. In previous work we showed that functional gene modules, which act distinctly in the course of development, can be represented by a mixture of trees. In general, the similarities in the gene expression programs of cell populations reflect the similarities in the differentiation path. Results: We propose a novel model for gene expression profiles and an unsupervised learning method to estimate developmental similarity and infer differentiation pathways. We assess the performance of our model on simulated data and compare it with favorable results to related methods. We also infer differentiation pathways and predict functional modules in gene expression data of lymphoid development. Conclusions: We demonstrate for the first time how, in principal, the incorporation of structural knowledge about the dependence structure helps to reveal differentiation pathways and potentially relevant functional gene modules from microarray datasets. Our method applies in any area of developmental biology where it is possible to obtain cells of distinguishable differentiation stages. Availability: The implementation of our method (GPL license), data and additional results are available at http://algorithmics.molgen.mpg.de/Supplements/InfDif/ Contact: filho@molgen.mpg.de, schliep@molgen.mpg.de Supplementary information: Supplementary data is available at Bioinformatics online. PMID:18586709

  10. Radionuclide measurement of differential glomerular filtration rate

    SciTech Connect

    Powers, T.A.; Stone, W.J.; Grove, R.B.; Plunkett, J.M.; Kadir, S.; Patton, J.A.; Bowen, R.D.

    1981-01-01

    The authors sought to determine whether radionuclides could provide a reasonable estimate of differential renal function in five normal dogs and six dogs with unilateral segmental renal infarction. Glomerular filtration rate (GFR) of each kidney was measured by the standard technique using constant infusions of 99mTc-DTPA, iothalamate, and creatinine following ureteral catheterization. These results were correlated with total GFR estimated by bolus injection of 99mTc-DTPA and analysis of the plasma 99mTc-DTPA disappearance curve obtained by blood sampling. Differential GFR was then calculated by multiplying the total GFR from double exponential analysis of this curve (DTPA2) by each of three measures of differential function. These include the percent differential uptake of 99mTc-DTPA and 99mTc-DMSA in the posterior projection as well as the geometric mean of 99mTc-DMSA uptake. There were good correlations between differential GFR calculated from iothalamate clearances obtained at ureteral catheterization and all noninvasive methods involving radionuclides and DTPA2 (r = 0.85 - 0.99). Single exponential analysis of the 99mTc-DTPA plasma disappearance curve was less satisfactory. The authors suggest that measurement of total and differential GFR calculated from plasma clearance of 99mTc-DTPA and external counting may be a useful method with potential clinical applications.

  11. Quantification of differential diffusion in nonpremixed systems.

    SciTech Connect

    Smith, Philip J.; Sutherland, James C.; Chen, Jacqueline H.

    2004-06-01

    Most attempts to quantify differential diffusion (DD) are based on the difference between different definitions of the mixture fraction. This paper presents a general method for evaluating differential diffusion in premixed or nonpremixed systems based on conservation equations for the elemental mass fractions. These measures form a basis for analyzing differential diffusion. Casting these in terms of a mixture fraction gives particular insight into differential diffusion for nonpremixed systems, and provides a single DD measure. Furthermore, it allows direct evaluation of the validity of the traditional assumptions involved in writing a mixture fraction transport equation. Results are presented for one-dimensional opposed flow simulations of hydrogen and methane flames as well as direct numerical simulations (DNS) of CH 4 /H 2 -air and CO/H 2 -air flames. For a common definition of the mixture fraction, the DD measure can be approximated well by considering only the contribution of H 2 and CH 4 in methane-air flames. Differential diffusion is largely driven by production of H 2 in the flame zone for hydrocarbon flames. Effects of strain rate and filter width on the relative importance of differential diffusion are examined.

  12. Building Measures of Instructional Differentiation from Teacher Checklists

    ERIC Educational Resources Information Center

    Williams, Ryan; Swanlund, Andrew; Miller, Shazia; Konstantopoulos, Spyros; van der Ploeg, Arie

    2012-01-01

    Differentiated instruction is commonly believed to be critical to improving the quality and efficiency of teachers' instructional repertoires (Fischer & Rose, 2001; Tomlinson, 2004). Tomlinson (2000) describes differentiation in four domains: content, process, product, and learning environment. Content differentiation involves varying…

  13. Protein kinase C isoforms play differential roles in the regulation of adipocyte differentiation.

    PubMed Central

    Fleming, I; MacKenzie, S J; Vernon, R G; Anderson, N G; Houslay, M D; Kilgour, E

    1998-01-01

    In this study we first established, by immunoblotting with specific antibodies, the temporal changes in cellular levels of protein kinase C (PKC) isoforms during differentiation of 3T3-F442A pre-adipocytes. Both pre-adipocyte and adipocyte 3T3-F442A cells were found to express PKC-alpha, -gamma, -delta, -epsilon, -zeta and -mu. However we were unable to detect PKC-beta, -eta or -theta. The same PKC isoform expression profile was found in rat adipocytes. The alpha, delta and gamma isoforms displayed similar temporal patterns of expression during differentiation of 3T3-F442A cells; all increased rapidly, peaking at day 2 of differentiation. Subsequently, the expression of these isoforms decreased, resulting in lower levels in fully differentiated adipocytes than in pre-adipocytes. The expression of PKC-epsilon increased steadily during differentiation, resulting in markedly elevated levels in adipocytes. Although expression of PKC-mu increased during differentiation, this was attributable to prolonged confluence rather than to the differentiation process itself. No change was observed in PKC-zeta levels during adipocyte development. Anti-sense oligodeoxynucleotides (ODNs) were used to deplete selectively the individual PKC subtypes. Each of the ODNs used effectively depleted the specific isoforms to undetectable levels and did not affect expression of the other PKC subtypes. This approach indicated that pre-adipocyte differentiation is not dependent upon PKC-zeta but that PKC-alpha,-delta and -mu each exert an inhibitory influence upon differentiation. Use of anti-sense ODNs to deplete PKC-epsilon and -gamma revealed that pre-adipocyte differentiation is dependent upon each of these isoforms. However, PKC-gamma, but not PKC-epsilon, appeared to be necessary for the clonal expansion of differentiating cells, suggesting that PKC-epsilon is required at a later phase in the differentiation process, when its expression is elevated, for the attainment and maintenance of

  14. Differentiation of Keratinocytes Modulates Skin HPA Analog.

    PubMed

    Wierzbicka, Justyna M; Żmijewski, Michał A; Antoniewicz, Jakub; Sobjanek, Michal; Slominski, Andrzej T

    2017-01-01

    It is well established, that epidermal keratinocytes express functional equivalent of hypothalamus-pituitary-adrenal axis (HPA) in order to respond to changing environment and maintain internal homeostasis. We are presenting data indicating that differentiation of primary neonatal human keratinocytes (HPEKp), induced by prolonged incubation or calcium is accompanied by significant changes in the expression of the elements of skin analog of HPA (sHPA). Expression of CRF, UCN1-3, POMC, ACTH, CRFR1, CRFR2, MC1R, MC2R, and GR (coded by NR3C1 gene) were observed on gene/protein levels along differentiation of keratinocytes in culture with similar pattern seen by immunohistochemistry on full thickness skin biopsies. Expression of CRF was more pronounced in less differentiated keratinocytes, which corresponded to the detection of CRF immunoreactivity preferentially in the stratum basale. POMC expression was enhanced in more differentiated keratinocytes, which corresponded to detection of ACTH immunoreactivity, predominantly in the stratum spinosum and stratum granulosum. Expression of urocortins was also affected by induction of HPEKp differentiation. Immunohistochemical studies showed high prevalence of CRFR1 in well differentiated keratinocytes, while smaller keratinocytes showed predominantly CRFR2 immunoreactivity. MC2R mRNA levels were elevated from days 4 to 8 of in vitro incubation, while MC2R immunoreactivity was the highest in the upper layers of epidermis. Similar changes in mRNA/protein levels of sHPA elements were observed in HPEKp keratinocytes treated with calcium. Summarizing, preferential expression of CRF and POMC (ACTH) by populations of keratinocytes on different stage of differentiation resembles organization of central HPA axis suggesting their distinct role in physiology and pathology of the epidermis. J. Cell. Physiol. 232: 154-166, 2017. © 2016 Wiley Periodicals, Inc.

  15. Opioids and differentiation in human cancer cells.

    PubMed

    Zagon, Ian S; McLaughlin, Patricia J

    2005-10-01

    This study was designed to examine the role of opioids on cell differentiation, with an emphasis on the mechanism of opioid growth factor (OGF, [Met5]-enkephalin)-dependent growth inhibition. Three human cancer cell lines (SK-N-SH neuroblastoma and SCC-1 and CAL-27 squamous cell carcinoma of the head and neck), along with OGF and the opioid antagonist naltrexone (NTX) at a dosage (10(-6) M) known to repress or increase, respectively, cell replication, were utilized. The effects on differentiation (neurite formation, process lengths, betaIII-tubulin, involucrin) were investigated in cells exposed to OGF or NTX for up to 6 days. In addition, the influence of a variety of other natural and synthetic opioids on differentiation was examined. OGF, NTX, naloxone, [D-Pen2,5]-enkephalin, dynorphin A1-8, beta-endorphin, endomorphin-1 and -2, [D-Ala2, MePhe4, Glycol5]-enkephalin (DAMGO), morphine, and U69,593 at concentrations of 10(-6) M did not alter cell differentiation of any cancer cell line. In NTX-treated SK-N-SH cells, cellular area was increased 23%, and nuclear area was decreased 17%, from control levels; no changes in cell or nuclear area were recorded in OGF-exposed cells. F-actin concentration was increased 40% from control values in SK-N-SH cells subjected to NTX, whereas alpha-tubulin was decreased 53% in OGF-treated cells. These results indicate that the inhibitory or stimulatory actions of OGF and NTX, respectively, on cell growth in tissue culture are not due to alterations in differentiation pathways. However, exposure to OGF and NTX modified some aspects of cell structure, but this was independent of differentiation. The absence of effects on cancer cell differentiation by a variety of other opioids supports the previously reported lack of growth effects of these compounds.

  16. Neurogenic differentiation of amniotic fluid stem cells.

    PubMed

    Rosner, M; Mikula, M; Preitschopf, A; Feichtinger, M; Schipany, K; Hengstschläger, M

    2012-05-01

    In 2003, human amniotic fluid has been shown to contain stem cells expressing Oct-4, a marker for pluripotency. This finding initiated a rapidly growing and very promising new stem cell research field. Since then, amniotic fluid stem (AFS) cells have been demonstrated to harbour the potential to differentiate into any of the three germ layers and to form three-dimensional aggregates, so-called embryoid bodies, known as the principal step in the differentiation of pluripotent stem cells. Marker selection and minimal dilution approaches allow the establishment of monoclonal AFS cell lineages with high proliferation potential. AFS cells have a lower risk for tumour development and do not raise the ethical issues of embryonic stem cells. Compared to induced pluripotent stem cells, AFS cells do not need exogenic treatment to induce pluripotency, are chromosomal stable and do not harbour the epigenetic memory and accumulated somatic mutations of specific differentiated source cells. Compared to adult stem cells, AFS can be grown in larger quantities and show higher differentiation potential. Accordingly, in the recent past, AFS became increasingly accepted as an optimal tool for basic research and probably also for specific cell-based therapies. Here, we review the current knowledge on the neurogenic differentiation potential of AFS cells.

  17. Troglitazone induces differentiation in Trypanosoma brucei

    SciTech Connect

    Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline; Brems, Stefanie; Busold, Christian; Lang, Florian; Hoheisel, Joerg; Duszenko, Michael . E-mail: michael.duszenko@uni-tuebingen.de

    2007-05-15

    Trypanosoma brucei, a protozoan parasite causing sleeping sickness, is transmitted by the tsetse fly and undergoes a complex lifecycle including several defined stages within the insect vector and its mammalian host. In the latter, differentiation from the long slender to the short stumpy form is induced by a yet unknown factor of trypanosomal origin. Here we describe that some thiazolidinediones are also able to induce differentiation. In higher eukaryotes, thiazolidinediones are involved in metabolism and differentiation processes mainly by binding to the intracellular receptor peroxisome proliferator activated receptor {gamma}. Our studies focus on the effects of troglitazone on bloodstream form trypanosomes. Differentiation was monitored using mitochondrial markers (membrane potential, succinate dehydrogenase activity, inhibition of oxygen uptake by KCN, amount of cytochrome transcripts), morphological changes (Transmission EM and light microscopy), and transformation experiments (loss of the Variant Surface Glycoprotein coat and increase of dihydroliponamide dehydrogenase activity). To further investigate the mechanisms responsible for these changes, microarray analyses were performed, showing an upregulation of expression site associated gene 8 (ESAG8), a potential differentiation regulator.

  18. Chromatin States Accurately Classify Cell Differentiation Stages

    PubMed Central

    Larson, Jessica L.; Yuan, Guo-Cheng

    2012-01-01

    Gene expression is controlled by the concerted interactions between transcription factors and chromatin regulators. While recent studies have identified global chromatin state changes across cell-types, it remains unclear to what extent these changes are co-regulated during cell-differentiation. Here we present a comprehensive computational analysis by assembling a large dataset containing genome-wide occupancy information of 5 histone modifications in 27 human cell lines (including 24 normal and 3 cancer cell lines) obtained from the public domain, followed by independent analysis at three different representations. We classified the differentiation stage of a cell-type based on its genome-wide pattern of chromatin states, and found that our method was able to identify normal cell lines with nearly 100% accuracy. We then applied our model to classify the cancer cell lines and found that each can be unequivocally classified as differentiated cells. The differences can be in part explained by the differential activities of three regulatory modules associated with embryonic stem cells. We also found that the “hotspot” genes, whose chromatin states change dynamically in accordance to the differentiation stage, are not randomly distributed across the genome but tend to be embedded in multi-gene chromatin domains, and that specialized gene clusters tend to be embedded in stably occupied domains. PMID:22363642

  19. Effect of Gravity on Monocyte Differentiation

    NASA Astrophysics Data System (ADS)

    Hughes-Fulford, Millie; Chang, Tammy T.; Li, Chai-Fei

    2008-06-01

    Early space flight experiments have shown that microgravity suppresses the immune response in humans, especially in T- cells activation and monocyte differentiation. Protein Kinase C (PKC) is a key protein controlling growth and differentiation of monocytes into macrophages. Previous studies by Hatton et al. showed that the distribution, cellular quantity and kinetics of translocation of PKC are altered in microgravity. We have conducted studies of PKC activation using phorbol 12,13-dibutyrate (PDBu) under normal and altered gravity on our PKINASE experiment on ISS. Examination of differentiation of monocytes under real microgravity and normal gravity show significant changes in the molecular function gene expression during early signalling as well as in expression of differentiation of the monocyte. PDBu causes differentiation of the monocyte and results in adhesion of the cells within 24 hours. Cumulatively, these results suggest that activation of early signal transduction is regulated in part by gravity. In true microgravity (μg) we see significant changes in gene expression of the monocyte between activation of the μg samples and the 1g in-flight samples. These changes in gene expression suggest a role of gravity in regulation of immune function in human monoctytes. (Supported by NASA NCC 2-1361 and many thanks to the teams of ESA, ESTEC, ESA-Moscow, IBMP, Baikonur labs and the Cosmonauts for making this experiment possible).

  20. Mechanisms of Giardia lamblia differentiation into cysts.

    PubMed Central

    Luján, H D; Mowatt, M R; Nash, T E

    1997-01-01

    Microbiologists have long been intrigued by the ability of parasitic organisms to adapt to changes in the environment. Since most parasites occupy several niches during their journey between vectors and hosts, they have developed adaptive responses which allow them to survive under adverse conditions. Therefore, the life cycles of protozoan and helminthic parasites are excellent models with which to study numerous mechanisms involved in cell differentiation, such as the regulation of gene expression, signal transduction pathways, and organelle biogenesis. Unfortunately, many of these studies are very difficult because the conditions needed to elicit developmental changes in parasites remain undetermined in most cases. Recently, several interesting findings were reported on the process of differentiation of Giardia lamblia trophozoites into cysts. G. lamblia is a flagellated protozoan that inhabits the upper small intestine of its vertebrate host and is a major cause of enteric disease worldwide. It belongs to the earliest identified lineage among eukaryotes and therefore offers a unique insight into the progression from primitive to more complex eukaryotic cells. The discovery of a specific stimulus that induces trophozoites to differentiate into cysts, the identification and characterization of encystation-specific molecules, the elucidation of novel biochemical pathways, and the development of useful reagents and techniques have made this parasite an excellent model with which to study differentiation in eukaryotic cells. In this review, we summarize the most recent fundings on several aspects of Giardia differentiation and discuss the significance of these findings within the context of current knowledge in the field. PMID:9293183

  1. Comparative network analysis via differential graphlet communities

    PubMed Central

    Wong, Serene W H; Cercone, Nick; Jurisica, Igor

    2015-01-01

    While current protein interaction data provides a rich resource for molecular biology, it mostly lacks condition-specific details. Abundance of mRNA data for most diseases provides potential to model condition-specific transcriptional changes. Transcriptional data enables modeling disease mechanisms, and in turn provide potential treatments. While approaches to compare networks constructed from healthy and disease samples have been developed, they do not provide the complete comparison, evaluations are performed on very small networks, or no systematic network analyses are performed on differential network structures. We propose a novel method for efficiently exploiting network structure information in the comparison between any graphs, and validate results in non-small cell lung cancer. We introduce the notion of differential graphlet community to detect deregulated subgraphs between any graphs such that the network structure information is exploited. The differential graphlet community approach systematically captures network structure differences between any graphs. Instead of using connectivity of each protein or each edge, we used shortest path distributions on differential graphlet communities in order to exploit network structure information on identified deregulated subgraphs. We validated the method by analyzing three non-small cell lung cancer datasets and validated results on four independent datasets. We observed that the shortest path lengths are significantly longer for normal graphs than for tumor graphs between genes that are in differential graphlet communities, suggesting that tumor cells create "shortcuts" between biological processes that may not be present in normal conditions. PMID:25283527

  2. Exploring the cell signalling in hepatocyte differentiation.

    PubMed

    Vasconcellos, Rebecca; Alvarenga, Érika C; Parreira, Ricardo C; Lima, Swiany S; Resende, Rodrigo R

    2016-11-01

    The liver is the second largest organ in the human body and is responsible for several functions that directly contribute to homeostasis. Hepatocytes are the main parenchymal liver cells that regulate multiple biochemical and metabolic functions and the synthesis of substances important to the body. Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesoderm, which can be obtained from various tissues. Under certain conditions, MSCs can differentiate into several cell types, including hepatocytes. Post-transcriptional regulations of liver development signalling and hepatocyte differentiation have been demonstrated. At the post-transcriptional level, microRNAs have emerged as precursors for determining cell fate during differentiation. MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of gene expression. They can determine the stem cell fate by repressing the translation of target mRNAs. In this review, we outline signalling pathways involved in stem cell differentiation to hepatocytes and its interplay with liver development. Hepatic differentiation models in two-dimensional and three-dimensional cultures used to analyse signalling mechanisms will be described. We also highlight the possible miRNAs involved in this process and the transdifferentiation signalling mechanisms present in hepatocytes.

  3. Exploring the cell signalling in hepatocyte differentiation.

    PubMed

    Vasconcellos, Rebecca; Alvarenga, Érika C; Parreira, Ricardo C; Lima, Swiany S; Resende, Rodrigo R

    2016-11-01

    The liver is the second largest organ in the human body and is responsible for several functions that directly contribute to homeostasis. Hepatocytes are the main parenchymal liver cells that regulate multiple biochemical and metabolic functions and the synthesis of substances important to the body. Mesenchymal stem cells (MSCs) are a group of stem cells derived from the mesoderm, which can be obtained from various tissues. Under certain conditions, MSCs can differentiate into several cell types, including hepatocytes. Post-transcriptional regulations of liver development signalling and hepatocyte differentiation have been demonstrated. At the post-transcriptional level, microRNAs have emerged as precursors for determining cell fate during differentiation. MicroRNAs (miRNAs) are small non-coding RNAs involved in the post-transcriptional regulation of gene expression. They can determine the stem cell fate by repressing the translation of target mRNAs. In this review, we outline signalling pathways involved in stem cell differentiation to hepatocytes and its interplay with liver development. Hepatic differentiation models in two-dimensional and three-dimensional cultures used to analyse signalling mechanisms will be described. We also highlight the possible miRNAs involved in this process and the transdifferentiation signalling mechanisms present in hepatocytes. PMID:27555287

  4. Heterocyst differentiation in the cyanobacterium Mastigocladus laminosus

    SciTech Connect

    Nierzwicki-Bauer, S.A.; Balkwill, D.L.; Stevens, S.E. Jr.

    1984-02-01

    The morphological and ultrastructural aspects of heterocyst differentiation in the branching, filamentous cyanobacterium Mastigocladus laminosus were examined with light and electron microscopy. The earliest differentation stages involved cytoplasmic changes, including rapid degradation of carboxysomes, degradation of polysaccharide granules, and accumulation of electron-dense ribosomal or protein material (or both). Intermediate differentiation stages involved synthesis of a homogeneous extra wall layer development of necks leading to adjacent cells, and elaboration of a complex system of intracytoplasmic membranes. Late differentiation stages included further development of necks and continued elaboration of membranes. Mature heterocysts possessed a uniformly electron-dense cytoplasm that contained large numbers of closely packed membranes, some of which were arranged in lamellar stacks. Mature heterocysts lacked all of the inclusion bodies present in undifferentiated vegetative cells, but contained a number of unusual spherical inclusions of variable electron density. Cells in both narrow and wide filaments were capable of differentiating. Heterocysts developed at a variety of locations in the wide, branching filaments, although the majority of them were situated adjacent to branch points. M. laminosus displayed a marked tendency to produce sets of adjacent heterocysts or proheterocysts (or both) that were not separated from each other by vegetative cells. Groups of four or more adjacent heterocysts or proheterocysts occurred frequently in wide filaments, and in some of these filaments virtually all of the cells appeared to be capable of differentiating into heterocysts.

  5. Chromoplast differentiation: current status and perspectives.

    PubMed

    Egea, Isabel; Barsan, Cristina; Bian, Wanping; Purgatto, Eduardo; Latché, Alain; Chervin, Christian; Bouzayen, Mondher; Pech, Jean-Claude

    2010-10-01

    Chromoplasts are carotenoid-accumulating plastids conferring color to many flowers and fruits as well as to some tubers and roots. Chromoplast differentiation proceeds from preexisting plastids, most often chloroplasts. One of the most prominent changes is remodeling of the internal membrane system associated with the formation of carotenoid-accumulating structures. During the differentiation process the plastid genome is essentially stable and transcriptional activity is restricted. The buildup of the chromoplast for specific metabolic characteristics is essentially dependent upon the transcriptional activity of the nucleus. Important progress has been made in terms of mediation of the chloroplast-to-chromoplast transition with the discovery of the crucial role of the Or gene. In this article we review recent developments in the structural, biochemical and molecular aspects of chromoplast differentiation and also consider the reverse differentiation of chromoplasts into chloroplast-like structures during the regreening process occurring in some fruit. Future perspectives toward a full understanding of chromoplast differentiation include in-depth knowledge of the changes occurring in the plastidial proteome during chromoplastogenesis, elucidation of the role of hormones and the search for signals that govern the dialog between the nuclear and the chromoplastic genome.

  6. Quantifying the measurement of differential diagnosis.

    PubMed

    Johnson, L A

    1995-01-01

    Differential diagnosis is central to the work and training of all health care professionals. To develop solid differential diagnosis and skills, students required practice diagnosing numerous and varied patients. In the absence of real patients, patient simulations are commonly used to provide this range of diagnostic experiences. This study examined the benefits of interactive patient simulations on the diagnostic approaches of beginning dental students (novices) and practicing dentists (experts). The study tested the hypothesis that novices tend to use trial-and-error, while experts tend to use pattern recognition during differential diagnosis. a second goal of the study explored objective and subjective measures of a differential diagnosis approach. Seventy-five subjects comprised two treatment groups: a novice group and an expert group. Each group completed ten patient simulations and a case study test measured the diagnostic approach. A three factor MANOVA (p>0.05) was followed by univariate ANOVA's. The result indicated differences between the diagnostic approaches of experts and novices and that the subjective Ratings and the objective Maximum Decisions and Average Variation variables were the best measures of a differential diagnostic approach. PMID:8591429

  7. Differentiation Is an Expectation: A School Leader's Guide to Building a Culture of Differentiation

    ERIC Educational Resources Information Center

    Hewitt, Kimberly Kappler; Weckstein, Daniel K.

    2011-01-01

    Turn your school into a place where every child achieves. This book provides leaders with all that they need to promote differentiation in their schools and districts. Through research and first-hand experience, the authors have identified effective strategies for hiring differentiation-minded staff members, communicating the need for…

  8. Detecting Differential Item Functioning and Differential Step Functioning due to Differences that "Should" Matter

    ERIC Educational Resources Information Center

    Miller, Tess; Chahine, Saad; Childs, Ruth A.

    2010-01-01

    This study illustrates the use of differential item functioning (DIF) and differential step functioning (DSF) analyses to detect differences in item difficulty that are related to experiences of examinees, such as their teachers' instructional practices, that are relevant to the knowledge, skill, or ability the test is intended to measure. This…

  9. Differential Susceptibility Experiments: Going beyond Correlational Evidence--Comment on beyond Mental Health, Differential Susceptibility Articles

    ERIC Educational Resources Information Center

    van IJzendoorn, Marinus H.; Bakermans-Kranenburg, Marian J.

    2012-01-01

    Reviewing the studies on differential susceptibility presented in this section, we argue that the time is ripe to go beyond correlational designs to differential susceptibility experiments. In such experiments, randomization prevents hidden moderator effects on the environment and guarantees the independence of moderator and outcome, while the…

  10. Increasing Performance by Differentiated Teaching? Experimental Evidence of the Student Benefits of Digital Differentiation

    ERIC Educational Resources Information Center

    Haelermans, Carla; Ghysels, Joris; Prince, Fernao

    2015-01-01

    This paper explores the effect of digital differentiation on student performance using a randomized experiment. The experiment is conducted in a second year biology class among 115 prevocational students in the Netherlands. Differentiation allowed students in the treatment group to work at three different levels. The results show that there is a…

  11. To Differentiate or Not to Differentiate? Using Internet-Based Technology in the Classroom

    ERIC Educational Resources Information Center

    Cobb, Aries

    2010-01-01

    In the targeted school in the Cleveland Metropolitan School District, teachers focus on differentiating instruction with technology-based software. Differentiated instruction is the chosen teaching strategy over direct instruction because students and teachers alike prefer to work in cooperative groups while using technology in the classroom.…

  12. Analysis of backward differentiation formula for nonlinear differential-algebraic equations with 2 delays.

    PubMed

    Sun, Leping

    2016-01-01

    This paper is concerned with the backward differential formula or BDF methods for a class of nonlinear 2-delay differential algebraic equations. We obtain two sufficient conditions under which the methods are stable and asymptotically stable. At last, examples show that our methods are true. PMID:27441132

  13. Differentiation in Practice: A Resource Guide for Differentiating Curriculum, Grades 9-12

    ERIC Educational Resources Information Center

    Tomlinson, Carol Ann; Strickland, Cindy A.

    2005-01-01

    Join Carol Ann Tomlinson and Cindy A. Strickland in the continuing exploration of how real teachers incorporate differentiation principles and strategies throughout an entire instructional unit. Focusing on the high school grades, but applicable at all levels, Differentiation in Practice, Grades 9?12 will teach anyone interested in designing and…

  14. Differential equation models for sharp threshold dynamics.

    PubMed

    Schramm, Harrison C; Dimitrov, Nedialko B

    2014-01-01

    We develop an extension to differential equation models of dynamical systems to allow us to analyze probabilistic threshold dynamics that fundamentally and globally change system behavior. We apply our novel modeling approach to two cases of interest: a model of infectious disease modified for malware where a detection event drastically changes dynamics by introducing a new class in competition with the original infection; and the Lanchester model of armed conflict, where the loss of a key capability drastically changes the effectiveness of one of the sides. We derive and demonstrate a step-by-step, repeatable method for applying our novel modeling approach to an arbitrary system, and we compare the resulting differential equations to simulations of the system's random progression. Our work leads to a simple and easily implemented method for analyzing probabilistic threshold dynamics using differential equations. PMID:24184349

  15. Cell proliferation and differentiation in chemical leukemogenesis

    NASA Technical Reports Server (NTRS)

    Irons, R. D.; Stillman, W. S.; Clarkson, T. W. (Principal Investigator)

    1993-01-01

    In tissues such as bone marrow with normally high rates of cell division, proliferation is tightly coordinated with cell differentiation. Survival, proliferation and differentiation of early hematopoietic progenitor cells depend on the growth factors, interleukin 3 (IL-3) and/or granulocyte-macrophage colony stimulating factor (GM-CSF) and their synergism with other cytokines. We provide evidence that a characteristic shared by a diverse group of compounds with demonstrated leukemogenic potential is the ability to act synergistically with GM-CSF. This results in an increase in recruitment of a resting population of hematopoietic progenitor cells normally unresponsive to the cytokine and a twofold increase in the size of the proliferating cell population normally regarded to be at risk of transformation in leukemogenesis. These findings support the possibility that transient alterations in hematopoietic progenitor cell differentiation may be an important factor in the early stages of development of leukemia secondary to chemical or drug exposure.

  16. Top differential cross section measurements (Tevatron)

    SciTech Connect

    Jung, Andreas W.

    2012-01-01

    Differential cross sections in the top quark sector measured at the Fermilab Tevatron collider are presented. CDF used 2.7 fb{sup -1} of data and measured the differential cross section as a function of the invariant mass of the t{bar t} system. The measurement shows good agreement with the standard model and furthermore is used to derive limits on the ratio {kappa}/M{sub Pl} for gravitons which decay to top quarks in the Randall-Sundrum model. D0 used 1.0 fb{sup -1} of data to measure the differential cross section as a function of the transverse momentum of the top-quark. The measurement shows a good agreement to the next-to-leading order perturbative QCD prediction and various other standard model predictions.

  17. Biophysical regulation of stem cell differentiation.

    PubMed

    Govey, Peter M; Loiselle, Alayna E; Donahue, Henry J

    2013-06-01

    Bone adaptation to its mechanical environment, from embryonic through adult life, is thought to be the product of increased osteoblastic differentiation from mesenchymal stem cells. In parallel with tissue-scale loading, these heterogeneous populations of multipotent stem cells are subject to a variety of biophysical cues within their native microenvironments. Bone marrow-derived mesenchymal stem cells-the most broadly studied source of osteoblastic progenitors-undergo osteoblastic differentiation in vitro in response to biophysical signals, including hydrostatic pressure, fluid flow and accompanying shear stress, substrate strain and stiffness, substrate topography, and electromagnetic fields. Furthermore, stem cells may be subject to indirect regulation by mechano-sensing osteocytes positioned to more readily detect these same loading-induced signals within the bone matrix. Such paracrine and juxtacrine regulation of differentiation by osteocytes occurs in vitro. Further studies are needed to confirm both direct and indirect mechanisms of biophysical regulation within the in vivo stem cell niche.

  18. Punicalagin promotes human villous trophoblast differentiation.

    PubMed

    Chen, Baosheng; Longtine, Mark S; Costa, Maria Laura; Nelson, D Michael

    2016-08-01

    Poor differentiation of trophoblasts is associated with placental dysfunction, predisposing women to multiple pregnancy disorders. Punicalagin, a prominent ellagitannin in pomegranate juice has been shown to exert anti-apoptosis and anti-oxidative effects in human trophoblasts. We hypothesized that punicalagin modulates trophoblast differentiation. We found that punicalagin-treated primary trophoblast showed reduced E-cadherin, higher Syncytin 1, more β-hCG, and increased GCM1, an upstream regulator of β-hCG. Punicalagin exposure of villous explants enhanced the number of cytotrophoblasts expressing the proliferation marker Ki67. We conclude that punicalagin enhances trophoblast differentiation and speculate that punicalagin might be used therapeutically in pregnancies at risk for placental dysfunction. PMID:27452441

  19. Samples from Differentiated Asteroids; Regolithic Achondrites

    NASA Technical Reports Server (NTRS)

    Herrin J. S.; Ross, A. J.; Cartwright, J. A.; Ross, D. K.; Zolensky, Michael E.; Jenniskens, P.

    2011-01-01

    Differentiated and partially differentiated asteroids preserve a glimpse of planet formation frozen in time from the early solar system and thus are attractive targets for future exploration. Samples of such asteroids arrive to Earth in the form of achondrite meteorites. Many achondrites, particularly those thought to be most representative of asteroidal regolith, contain a diverse assortment of materials both indigenous and exogenous to the original igneous parent body intermixed at microscopic scales. Remote sensing spacecraft and landers would have difficulty deciphering individual components at these spatial scales, potentially leading to confusing results. Sample return would thus be much more informative than a robotic probe. In this and a companion abstract [1] we consider two regolithic achondrite types, howardites and (polymict) ureilites, in order to evaluate what materials might occur in samples returned from surfaces of differentiated asteroids and what sampling strategies might be prudent.

  20. Differential Geometry and Lie Groups for Physicists

    NASA Astrophysics Data System (ADS)

    Fecko, Marián.

    2006-10-01

    Introduction; 1. The concept of a manifold; 2. Vector and tensor fields; 3. Mappings of tensors induced by mappings of manifolds; 4. Lie derivative; 5. Exterior algebra; 6. Differential calculus of forms; 7. Integral calculus of forms; 8. Particular cases and applications of Stoke's Theorem; 9. Poincaré Lemma and cohomologies; 10. Lie Groups - basic facts; 11. Differential geometry of Lie Groups; 12. Representations of Lie Groups and Lie Algebras; 13. Actions of Lie Groups and Lie Algebras on manifolds; 14. Hamiltonian mechanics and symplectic manifolds; 15. Parallel transport and linear connection on M; 16. Field theory and the language of forms; 17. Differential geometry on TM and T*M; 18. Hamiltonian and Lagrangian equations; 19. Linear connection and the frame bundle; 20. Connection on a principal G-bundle; 21. Gauge theories and connections; 22. Spinor fields and Dirac operator; Appendices; Bibliography; Index.

  1. Transcriptional Regulation of Th17 Cell Differentiation

    PubMed Central

    Ivanov, Ivaylo I.; Zhou, Liang; Littman, Dan R.

    2009-01-01

    The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been profoundly shaken by the discovery of T cells that secrete IL-17 and other inflammatory cytokines. This subset, referred to as Th17, is centrally involved in autoimmune disease and is important in host defense at mucosal surfaces. In mouse, a series of cytokines, including IL-6, IL-21, IL-23, and TGF-β, function sequentially or synergistically to induce the Th17 lineage. Other cytokines, including IL-2, IL-4, IFNγ, and IL-27, inhibit differentiation of this lineage. Here we review how the nuclear orphan receptor RORγt functions to coordinate the diverse cytokine-induced signals and thus control Th17 cell differentiation. PMID:18053739

  2. Signal transduction and Th17 cell differentiation

    PubMed Central

    O’Shea, John J.; Steward-Tharp, Scott M.; Laurence, Arian; Watford, Wendy T.; Wei, Lai; Adamson, Adewole S.; Fan, Samuel

    2009-01-01

    The paradigm of effector T helper cell differentiation into either Th1 or Th2 lineages has been notably shaken by the discovery of a third lineage of cells that selectively produce interleukin (IL)-17. Characterization of this new subset, referred to as Th17, has provided exciting new insights into immunoregulation, host defense and the pathogenesis of autoimmune diseases. Additionally, the discovery of this T cell subset has offered a fresh look at such concepts as lineage commitment and terminal differentiation. The transcriptional regulatory events and epigenetic modifications that control these processes are diverse and complex, and despite the rapid pace at which data continues to accumulate, many questions remain to be answered. Here we review our current understanding of the signaling pathways, molecular interactions and transcriptional events that lead to Th17 differentiation and effector function, as well as the epigenetic modifications that accompany them. PMID:19379825

  3. Differential memory in the earth's magnetotail

    NASA Technical Reports Server (NTRS)

    Burkhart, G. R.; Chen, J.

    1991-01-01

    The process of 'differential memory' in the earth's magnetotail is studied in the framework of the modified Harris magnetotail geometry. It is verified that differential memory can generate non-Maxwellian features in the modified Harris field model. The time scales and the potentially observable distribution functions associated with the process of differential memory are investigated, and it is shown that non-Maxwelllian distributions can evolve as a test particle response to distribution function boundary conditions in a Harris field magnetotail model. The non-Maxwellian features which arise from distribution function mapping have definite time scales associated with them, which are generally shorter than the earthward convection time scale but longer than the typical Alfven crossing time.

  4. How to (path-) integrate by differentiating

    NASA Astrophysics Data System (ADS)

    Kempf, Achim; Jackson, David M.; Morales, Alejandro H.

    2015-07-01

    Path integrals are at the heart of quantum field theory. In spite of their covariance and seeming simplicity, they are hard to define and evaluate. In contrast, functional differentiation, as it is used, for example, in variational problems, is relatively straightforward. This has motivated the development of new techniques that allow one to express functional integration in terms of functional differentiation. In fact, the new techniques allow one to express integrals in general through differentiation. These techniques therefore add to the general toolbox for integration and for integral transforms such as the Fourier and Laplace transforms. Here, we review some of these results, we give simpler proofs and we add new results, for example, on expressing the Laplace transform and its inverse in terms of derivatives, results that may be of use in quantum field theory, e.g., in the context of heat traces.

  5. Soft tissue differentiation by diffuse reflectance spectroscopy

    NASA Astrophysics Data System (ADS)

    Zam, Azhar; Stelzle, Florian; Nkenke, Emeka; Tangermann-Gerk, Katja; Schmidt, Michael; Adler, Werner; Douplik, Alexandre

    2009-07-01

    Laser surgery gives the possibility to work remotely which leads to high precision, little trauma and high level sterility. However these advantages are coming with the lack of haptic feedback during the laser ablation of tissue. Therefore additional means are required to control tissue-specific ablation during laser surgery supporting the surgeon regardless of experience and skills. Diffuse Reflectance Spectroscopy provides a straightforward and simple approach for optical tissue differentiation. We measured diffuse reflectance from four various tissue types ex vivo. We applied Linear Discriminant Analysis (LDA) to differentiate the four tissue types and computed the area under the ROC curve (AUC). Special emphasis was taken on the identification of nerve as the most crucial tissue for maxillofacial surgery. The results show a promise for differentiating soft tissues as guidance for tissue-specific laser surgery by means of the diffuse reflectance.

  6. Nonlinear self-adjointness through differential substitutions

    NASA Astrophysics Data System (ADS)

    Gandarias, M. L.

    2014-10-01

    It is known (Ibragimov, 2011; Galiakberova and Ibragimov, 2013) [14,18] that the property of nonlinear self-adjointness allows to associate conservation laws of the equations under study, with their symmetries. In this paper we show that, even when the equation is nonlinearly self-adjoint with a non differential substitution, finding the explicit form of the differential substitution can provide new conservation laws associated to its symmetries. By using the general theorem on conservation laws (Ibragimov, 2007) [11] and the property of nonlinear self-adjointness we find some new conservation laws for the modified Harry-Dym equation. By using a differential substitution we construct a conservation law for the Harry-Dym equation, which has not been derived before using Ibragimov method.

  7. Differential equation models for sharp threshold dynamics.

    PubMed

    Schramm, Harrison C; Dimitrov, Nedialko B

    2014-01-01

    We develop an extension to differential equation models of dynamical systems to allow us to analyze probabilistic threshold dynamics that fundamentally and globally change system behavior. We apply our novel modeling approach to two cases of interest: a model of infectious disease modified for malware where a detection event drastically changes dynamics by introducing a new class in competition with the original infection; and the Lanchester model of armed conflict, where the loss of a key capability drastically changes the effectiveness of one of the sides. We derive and demonstrate a step-by-step, repeatable method for applying our novel modeling approach to an arbitrary system, and we compare the resulting differential equations to simulations of the system's random progression. Our work leads to a simple and easily implemented method for analyzing probabilistic threshold dynamics using differential equations.

  8. Stochastic Differential Equation of Earthquakes Series

    NASA Astrophysics Data System (ADS)

    Mariani, Maria C.; Tweneboah, Osei K.; Gonzalez-Huizar, Hector; Serpa, Laura

    2016-07-01

    This work is devoted to modeling earthquake time series. We propose a stochastic differential equation based on the superposition of independent Ornstein-Uhlenbeck processes driven by a Γ (α, β ) process. Superposition of independent Γ (α, β ) Ornstein-Uhlenbeck processes offer analytic flexibility and provides a class of continuous time processes capable of exhibiting long memory behavior. The stochastic differential equation is applied to the study of earthquakes by fitting the superposed Γ (α, β ) Ornstein-Uhlenbeck model to earthquake sequences in South America containing very large events (Mw ≥ 8). We obtained very good fit of the observed magnitudes of the earthquakes with the stochastic differential equations, which supports the use of this methodology for the study of earthquakes sequence.

  9. Differential Geometry and Lie Groups for Physicists

    NASA Astrophysics Data System (ADS)

    Fecko, Marián.

    2011-03-01

    Introduction; 1. The concept of a manifold; 2. Vector and tensor fields; 3. Mappings of tensors induced by mappings of manifolds; 4. Lie derivative; 5. Exterior algebra; 6. Differential calculus of forms; 7. Integral calculus of forms; 8. Particular cases and applications of Stoke's Theorem; 9. Poincaré Lemma and cohomologies; 10. Lie Groups - basic facts; 11. Differential geometry of Lie Groups; 12. Representations of Lie Groups and Lie Algebras; 13. Actions of Lie Groups and Lie Algebras on manifolds; 14. Hamiltonian mechanics and symplectic manifolds; 15. Parallel transport and linear connection on M; 16. Field theory and the language of forms; 17. Differential geometry on TM and T*M; 18. Hamiltonian and Lagrangian equations; 19. Linear connection and the frame bundle; 20. Connection on a principal G-bundle; 21. Gauge theories and connections; 22. Spinor fields and Dirac operator; Appendices; Bibliography; Index.

  10. Laplace and the era of differential equations

    NASA Astrophysics Data System (ADS)

    Weinberger, Peter

    2012-11-01

    Between about 1790 and 1850 French mathematicians dominated not only mathematics, but also all other sciences. The belief that a particular physical phenomenon has to correspond to a single differential equation originates from the enormous influence Laplace and his contemporary compatriots had in all European learned circles. It will be shown that at the beginning of the nineteenth century Newton's "fluxionary calculus" finally gave way to a French-type notation of handling differential equations. A heated dispute in the Philosophical Magazine between Challis, Airy and Stokes, all three of them famous Cambridge professors of mathematics, then serves to illustrate the era of differential equations. A remark about Schrödinger and his equation for the hydrogen atom finally will lead back to present times.

  11. Adverse effects of differential parental attention1

    PubMed Central

    Sajwaj, Thomas E.; Pinkston, Susan; Cordua, Glenn; Jackson, Carolyn; Herbert, Emily W.; Pinkston, Elsie M.; Hayden, M. Loeman

    1973-01-01

    In two independent parent training projects (Kansas and Mississippi), mothers of deviant young children were observed to follow almost all child behaviors with attention. The mothers were then trained to use differential attention procedures to increase their child's appropriate behaviors and to decrease deviant behaviors. Contrary to expectations, the differential attention procedure produced substantial increases in deviant behavior for four of the children. This adverse effect was maintained over many sessions and was replicated in single organism, reversal designs. A fifth child showed no change. A sixth child showed some improvement. However, this effect was not recovered in a second application of differential attention, and the child became worse. The results underline the importance of subject generality in applied behavior analysis and strongly suggest that service programs using operant techniques must carefully evaluate their effects on behavior. PMID:16795386

  12. [Differential diagnosis between dissociative disorders and schizophrenia].

    PubMed

    Shibayama, Masatoshi

    2011-01-01

    The differential diagnosis of dissociative disorders includes many psychiatric disorders, such as schizophrenia, bipolar disorders (especially bipolar II disorder), depressive disorder (especially atypical depression), epilepsy, Asperger syndrome, and borderline personality disorder. The theme of this paper is the differential diagnosis between dissociative disorders and schizophrenia. Schneiderian first-rank symptoms in schizophrenia are common in dissociative disorders, especially in dissociative identity disorder (DID). Many DID patients have been misdiagnosed as schizophrenics and treated with neuroleptics. We compared and examined Schneiderian symptoms of schizophrenia and those of dissociative disorders from a structural viewpoint. In dissociative disorders, delusional perception and somatic passivity are not seen. "Lateness" and "Precedence of the Other" originated from the concept of "Pattern Reversal" (H. Yasunaga)" is characteristic of schizophrenia. It is important to check these basic structure of schizophrenia in subjective experiences in differential diagnosis between dissociative disorders and schizophrenia.

  13. Cisplatin Induces Differentiation of Breast Cancer Cells

    PubMed Central

    Prabhakaran, Praseetha; Hassiotou, Foteini; Blancafort, Pilar; Filgueira, Luis

    2013-01-01

    Breast tumors are heterogeneous including cells with stem cell properties and more differentiated cells. This heterogeneity is reflected into the molecular breast cancer subtypes. Breast cancer stem cells are resistant to chemotherapy, thus recent efforts are focusing on identifying treatments that shift them toward a more differentiated phenotype, making them more susceptible to chemotherapy. We examined whether the drug cisplatin induces differentiation in breast cancer cell lines that represent different breast cancer subtypes. We used three cell lines representing triple-negative breast cancers, BT-549 and MDA-MB-231 (claudin-low), and MDA-MB-468 (basal-like), along with estrogen and progesterone receptor positive MCF-7 cells (luminal). Cisplatin was applied at 2.5, 5, 10, and 20 μM, and cell viability and proliferation were measured using MTS and BrdU assays, respectively. The effect of cisplatin on the cellular hierarchy was examined by flow cytometry, immunofluorescence and qRT-PCR. Cisplatin treatment of 10 and 20 μM reduced cell viability by 36–51% and proliferation capacity by 36–67%. Treatment with cisplatin resulted in 12–67% down-regulation of stem cell markers (CD49f, SSEA4) and 10–130% up-regulation of differentiation markers (CK18, SMA, β-tubulin). At the mRNA level, CD49f was down-regulated whilst β-tubulin was up-regulated in the claudin-low cell lines. SSEA4 protein expression decreased upon cisplatin treatment, but SSEA4 mRNA expression increased indicating a differential regulation of cisplatin at the post-transcriptional level. It is concluded that cisplatin reduces breast cancer cell survival and induces differentiation of stem/progenitor cell subpopulations within breast cancer cell lines. These effects indicate the potential of this drug to target specific chemotherapy-resistant cells within a tumor. PMID:23761858

  14. Differential expression of Ran GTPase during HMBA-induced differentiation in murine erythroleukemia cells.

    PubMed

    Vanegas, N; García-Sacristán, A; López-Fernández, L A; Párraga, M; del Mazo, J; Hernández, P; Schvartzman, J B; Krimer, D B

    2003-07-01

    Murine erythroleukemia (MEL) cells undergo erythroid differentiation in vitro when treated with hexamethylene bisacetamide (HMBA). To identify genes involved in the commitment of MEL cells to differentiate, we screened a cDNA library constructed from HMBA-induced cells by differential hybridization and isolated GTPase Ran as a down-regulated gene. We observed that Ran was expressed in a biphasic mode. Following a decrease in mRNA level during the initial hours of induction, Ran re-expressed at 24-48 h, and gradually declined again. To investigate the role of Ran during MEL differentiation we constructed MEL transfectants capable to express or block Ran mRNA production constitutively. No effects were observed on cell growth and proliferation. Blockage of Ran, however, interfered with MEL cell differentiation resulting in a decrease of cell survival in the committed population.

  15. Protein turnover and differentiation in Leishmania

    PubMed Central

    Besteiro, Sébastien; Williams, Roderick A.M.; Coombs, Graham H.; Mottram, Jeremy C.

    2007-01-01

    Leishmania occurs in several developmental forms and thus undergoes complex cell differentiation events during its life-cycle. Those are required to allow the parasite to adapt to the different environmental conditions. The sequencing of the genome of L. major has facilitated the identification of the parasite’s vast arsenal of proteolytic enzymes, a few of which have already been carefully studied and found to be important for the development and virulence of the parasite. This review focuses on these peptidases and their role in the cellular differentiation of Leishmania through their key involvement in a variety of degradative pathways in the lysosomal and autophagy networks. PMID:17493624

  16. Modern differential pressure gas counter (WIGZ) measurement

    NASA Astrophysics Data System (ADS)

    Brandt, O.

    1985-07-01

    The differential pressure gas counter facility developed to measure gas flow rate on orifice plates in the pipe system transporting Soviet gas to West Germany and France was equipped with small computers which record all the parameters of a measuring system and calculate the standard volume and the quantity of heat. These parameters are used to calibrate the facility. The differential pressure indicators and operating densitometers, the standard densitometers, pressure and temperature sensors, and calorific value indicators are described. The operation of and processing by the 16-bit microprocessor computers of all parameters are summarized. The central computer and the performance recording facility are presented.

  17. A taxonomy of automatic differentiation tools

    SciTech Connect

    Juedes, D.W. . Dept. of Computer Science)

    1991-01-01

    Many of the current automatic differentiation (AD) tools have similar characteristics. Unfortunately, the similarities between these various AD tools often cannot be easily ascertained by reading the corresponding documentation. To clarify this situation, a taxonomy of AD tools is presented. The taxonomy places AD tools into the Elemental, Extensional, Integral, Operational, and Symbolic classes. This taxonomy is used to classify twenty-nine AD tools. Each tool is examined individually with respect to the mode of differentiation used and the degree of derivatives computed. A list detailing the availability of the surveyed AD tools is provided in the Appendix. 54 refs., 3 figs., 1 tab.

  18. Differentiation of 13 positive emotions by appraisals.

    PubMed

    Tong, Eddie M W

    2015-01-01

    This research examined how strongly appraisals can differentiate positive emotions and how they differentiate positive emotions. Thirteen positive emotions were examined, namely, amusement, awe, challenge, compassion, contentment, gratitude, hope, interest, joy, pride, relief, romantic love and serenity. Participants from Singapore and the USA recalled an experience of each emotion and thereafter rated their appraisals of the experience. In general, the appraisals accurately classified the positive emotions at rates above chance levels, and the appraisal-emotion relationships conformed to predictions. Also, the appraisals were largely judged by participants as relevant to their positive emotion experiences, and the appraisal-emotion relationships were largely consistent across the two countries. PMID:24911866

  19. Passive millimeter wave differential interference contrast polarimetry

    DOEpatents

    Bernacki, Bruce E; Kelly, James F; Sheen, David M; Tedeschi, Jonathan R; Hall, Thomas E; Hatchell, Brian K; Valdez, Patrick; McMakin, Douglas L

    2014-04-29

    Differential polarization imaging systems include an axicon configured to provide a displacement of ray bundles associated with different image patches. The displaced ray bundles are directed to antenna horns and orthomode transducers so as to provide outputs correspond to orthogonal linear states of polarization (SOPs). The outputs are directed to a differential radiometer so that Stokes parameter differences between image patches can be obtained. The ray bundle displacements can be selected to correspond to a mechanical spacing of antenna horns. In some examples, ray bundle displacement corresponds to a displacement less than the diffraction limit.

  20. Low-voltage differentially-signaled modulators.

    PubMed

    Zortman, William A; Lentine, Anthony L; Trotter, Douglas C; Watts, Michael R

    2011-12-19

    For exascale computing applications, viable optical solutions will need to operate using low voltage signaling and with low power consumption. In this work, the first differentially signaled silicon resonator is demonstrated which can provide a 5dB extinction ratio using 3fJ/bit and 500mV signal amplitude at 10Gbps. Modulation with asymmetric voltage amplitudes as low as 150mV with 3dB extinction are demonstrated at 10Gbps as well. Differentially signaled resonators simplify and expand the design space for modulator implementation and require no special drivers.

  1. First Theory Institute on Computational Differentiation

    SciTech Connect

    Bischof, C.H.; Griewank, A.; Khademi, P.M.

    1993-12-31

    Computational differentiation (CD) is concerned with tools, techniques, and mathematics for generating, with little human effort, efficient and accurate derivative codes from programs written in such computer languages as C and Fortran. The primary purposes of the meeting were to explore the deep complexity issues that lie at the heart of the computation of derivatives from computer programs and to provide a forum for brainstorming on future research directions, including the applications of automatic differentiation (AD) in scientific computing and the development of AD tools.

  2. Stem cell differentiation and human liver disease

    PubMed Central

    Zhou, Wen-Li; Medine, Claire N; Zhu, Liang; Hay, David C

    2012-01-01

    Human stem cells are scalable cell populations capable of cellular differentiation. This makes them a very attractive in vitro cellular resource and in theory provides unlimited amounts of primary cells. Such an approach has the potential to improve our understanding of human biology and treating disease. In the future it may be possible to deploy novel stem cell-based approaches to treat human liver diseases. In recent years, efficient hepatic differentiation from human stem cells has been achieved by several research groups including our own. In this review we provide an overview of the field and discuss the future potential and limitations of stem cell technology. PMID:22563188

  3. Algorithms For Integrating Nonlinear Differential Equations

    NASA Technical Reports Server (NTRS)

    Freed, A. D.; Walker, K. P.

    1994-01-01

    Improved algorithms developed for use in numerical integration of systems of nonhomogenous, nonlinear, first-order, ordinary differential equations. In comparison with integration algorithms, these algorithms offer greater stability and accuracy. Several asymptotically correct, thereby enabling retention of stability and accuracy when large increments of independent variable used. Accuracies attainable demonstrated by applying them to systems of nonlinear, first-order, differential equations that arise in study of viscoplastic behavior, spread of acquired immune-deficiency syndrome (AIDS) virus and predator/prey populations.

  4. Some problems in fractal differential equations

    NASA Astrophysics Data System (ADS)

    Su, Weiyi

    2016-06-01

    Based upon the fractal calculus on local fields, or p-type calculus, or Gibbs-Butzer calculus ([1],[2]), we suggest a constructive idea for "fractal differential equations", beginning from some special examples to a general theory. However, this is just an original idea, it needs lots of later work to support. In [3], we show example "two dimension wave equations with fractal boundaries", and in this note, other examples, as well as an idea to construct fractal differential equations are shown.

  5. Replication of prions in differentiated muscle cells.

    PubMed

    Herbst, Allen; Aiken, Judd M; McKenzie, Debbie

    2014-01-01

    We have demonstrated that prions accumulate to high levels in non-proliferative C2C12 myotubes. C2C12 cells replicate as myoblasts but can be differentiated into myotubes. Earlier studies indicated that C2C12 myoblasts are not competent for prion replication. (1) We confirmed that observation and demonstrated, for the first time, that while replicative myoblasts do not accumulate PrP(Sc), differentiated post-mitotic myotube cultures replicate prions robustly. Here we extend our observations and describe the implication and utility of this system for replicating prions.

  6. Rethinking differentiation: Stem cells, regeneration, and plasticity

    PubMed Central

    Alvarado, Alejandro Sánchez; Yamanaka, Shinya

    2014-01-01

    Cell differentiation is an essential process for the development, growth, reproduction and longevity of all multicellular organisms, and its regulation has been the focus of intense investigation for the past 4 decades. The study of natural and induced stem cells has ushered an age of re-examination of what it means to be a stem or a differentiated cell. Past and recent discoveries in plants and animals, as well as novel experimental manipulations are beginning to erode many of these established concepts, and are forcing a re-evaluation of the experimental systems and paradigms presently being used to explore these and other biological process. PMID:24679530

  7. Mesoderm Differentiation from hiPS Cells.

    PubMed

    Miwa, Hiroyuki; Era, Takumi

    2016-01-01

    Human induced pluripotent stem (hiPS) cells are very attractive tools for modeling diseases and regenerative medicine. However, to achieve them, the efficient differentiation methods of hiPS cells into aimed cell type in vitro are necessary. Because mesoderm cells are useful in particular, we have developed the differentiation of mouse embryonic stem (mES) cells into mesoderm cells previously. In this time, these methods were improved for hiPS cells and now human mesoderm cells are able to be obtained efficiently. It is certain that the new methods are applicable to various studies and therapies.

  8. Sparse dynamics for partial differential equations

    PubMed Central

    Schaeffer, Hayden; Caflisch, Russel; Hauck, Cory D.; Osher, Stanley

    2013-01-01

    We investigate the approximate dynamics of several differential equations when the solutions are restricted to a sparse subset of a given basis. The restriction is enforced at every time step by simply applying soft thresholding to the coefficients of the basis approximation. By reducing or compressing the information needed to represent the solution at every step, only the essential dynamics are represented. In many cases, there are natural bases derived from the differential equations, which promote sparsity. We find that our method successfully reduces the dynamics of convection equations, diffusion equations, weak shocks, and vorticity equations with high-frequency source terms. PMID:23533273

  9. Ca2+ signaling differentiation during oocyte maturation.

    PubMed

    Machaca, Khaled

    2007-11-01

    Oocyte maturation is an essential cellular differentiation pathway that prepares the egg for activation at fertilization leading to the initiation of embryogenesis. An integral attribute of oocyte maturation is the remodeling of Ca2+ signaling pathways endowing the egg with the capacity to produce a specialized Ca2+ transient at fertilization that is necessary and sufficient for egg activation. Consequently, mechanistic elucidation of Ca2+ signaling differentiation during oocyte maturation is fundamental to our understanding of egg activation, and offers a glimpse into Ca2+ signaling regulation during the cell cycle.

  10. Well-differentiated liposarcoma of the tongue.

    PubMed

    Nunes, F D; Loducca, S V L; de Oliveira, E M F; de Araújo, V C

    2002-01-01

    Intraoral liposarcomas are rare, with most reported cases being of the myxoid histological type. We present a well-differentiated liposarcoma of the tongue, in a 65-year-old man. The tumour presented lipoblasts in various stages of differentiation, lipocytes in different sizes and shapes, mesenchymal and signet-ring cells. Lipoma, spindle-cell lipoma, myxoma, hibernoma, angiolipoma, fibrolipoma, pseudosarcomatous faciitis and malignant hysticytoma were considered in the diagnosis process. The patient was treated surgically and so far is free of disease.

  11. Differential reinforcement with and without instructional fading.

    PubMed

    Ringdahl, Joel E; Kitsukawa, Kana; Andelman, Marc S; Call, Nathan; Winborn, Lisa; Barretto, Anjali; Reed, Gregory K

    2002-01-01

    We evaluated a differential-reinforcement-based treatment package for the reduction of problem behavior during instructional situations. Differential reinforcement of alternative behavior (DRA; compliance) was implemented across two conditions. During one condition, instructions were presented approximately once every other minute. This condition was considered the terminal goal for treatment. During the second condition, the rate of instructions was gradually increased (beginning at zero and ending when instruction rate was similar to the first condition). Results indicated that DRA with instructional fading resulted in less problem behavior than DRA without instructional fading. These results are similar to previous studies regarding the utility of instructional fading.

  12. Boolean differentiation and integration using Karnaugh maps

    NASA Technical Reports Server (NTRS)

    Tucker, J. H.; Tapia, M. A.; Bennett, A. W.

    1977-01-01

    Algorithms are presented for differentiation and integration of Boolean functions by means of Karnaugh maps. The algorithms are considered simple when the number of variables is six or less; in this case Boolean differentiation and integration is said to be as easy as the Karnaugh map method of simplifying switching functions. It is suggested that the algorithms would be useful in the analysis of faults in combinational systems and in the synthesis of asynchronous sequential systems which utilize edge-sensitive flip-flops.

  13. Teacher's Survival Guide: Differentiating Instruction in the Elementary Classroom

    ERIC Educational Resources Information Center

    Roberts, Julia L.; Inman, Tracy F.

    2012-01-01

    "Teacher's Survival Guide: Differentiating Instruction in the Elementary Classroom" answers the most common questions about differentiation, including what it is, how teachers can set up a classroom that promotes differentiation, which topics should be differentiated, what strategies are most effective, and how teachers can assess students engaged…

  14. A Vertical Differential Configuration in GPR prospecting

    NASA Astrophysics Data System (ADS)

    Persico, Raffaele; Pochanin, Gennadiy; Varianytsia-Roshchupkina, Liudmyla; Catapano, Ilaria; Gennarelli, Gianluca; Soldovieri, Francesco

    2015-04-01

    The rejection of the direct coupling between the antennas is an issue of interest in several GPR applications, especially when it is important to distinguish the targets of interest from the clutter and the signal reflected from the air soil interface. Therefore, in this framework several hardware and software strategies have been proposed. Among the software strategies, probably the most common one is the background removal [1], whereas as an hardware strategy the differential configuration has been introduced in [2-3] and then further on studied in [4] with respect to the spatial filtering properties of the relevant mathematical operator. In particular, the studies proposed in [1] and [4] have shown that, in general, all the strategies for the rejection of the direct coupling have necessarily some drawback, essentially because it is not possible to erase all and only the undesired contributions leaving "untouched" the contributions of the targets of interest to the gathered signal. With specific regard to the differential configuration, in [2-3], the differential configuration consisted in a couple of receiving antennas symmetrically placed around the transmitting one, being the three antennas placed along the same horizontal segment. Therefore, we might define that configuration as a "horizontal differential configuration". Here, we propose a novel differential GPR configuration, where the two receiving antennas are still symmetrically located with respect to the transmitting one, but are placed piled on each other at different heights from the air-soil interface, whereas the transmitting antenna is at the medium height between the two receiving one (however, it is not at the same abscissa but at a fixed horizontal offset from the receiving antennas). Such a differential configuration has been previously presented in [5-6] and allows a good isolation between the antennas, while preserving the possibility to collect backscattered signals from both electrically

  15. Computational Differential Equations: A Pilot Project

    ERIC Educational Resources Information Center

    Roubides, Pascal

    2004-01-01

    The following article presents a proposal for the redesign of a traditional course in Differential Equations at Middle Georgia College. The redesign of the course involves a new approach to teaching traditional concepts: one where the understanding of the physical aspects of each problem takes precedence over the actual mechanics of solving the…

  16. Intentions and Expectations in Differential Residential Selection

    ERIC Educational Resources Information Center

    Michelson, William; And Others

    1973-01-01

    This paper summarizes intentions and expectations in differential residential selection among families who had chose to move. Wives appear at face value to assess alternatives in the selection process rationally, to be aware of limitations in housing and location they will experience, and to have expectations about behavioral changes consistant…

  17. RTI & DI (Response to Intervention & Differentiated Instruction)

    ERIC Educational Resources Information Center

    Hanson, Helene M.

    2014-01-01

    In today's diverse and inclusive classrooms, teachers face the challenge of delivering instruction that is effective and accessible to students with a wide range of needs, abilities, and learning styles. Newly updated for 2014, "RTI & DI: Response to Intervention & Differentiated Instruction," by Helene Hanson, shows teachers how…

  18. Differential Outcomes of Early Childhood Education.

    ERIC Educational Resources Information Center

    Stevens, Jr., Joseph H.

    This paper reviews seven studies comparing the differential effects of early childhood programs and approaches on children's development: (1) Planned Variation in Head Start; (2) Planned Variation in Follow Through; (3) Soar and Soar Study of Follow Through; (4) Miller and Dyer's Planned Variations Study; (5) Karnes Curriculum Comparison Study;…

  19. Another Look at the Rules of Differentiation

    ERIC Educational Resources Information Center

    Cupillari, Antonella

    2004-01-01

    It is an eye opening experience for students to find out that even a great mathematician like Leibniz made mistakes, forgot to check carefully his calculations, and was temporarily misled by user-friendly but incorrect formulas. From Leibniz's mishap with the derivation of the rules of differentiation students can learn the importance of spending…

  20. Hypoxic Tumor Microenvironment and Cancer Cell Differentiation

    PubMed Central

    Kim, Yuri; Lin, Qun; Glazer, Peter M.; Yun, Zhong

    2010-01-01

    Hypoxia or oxygen deficiency is a salient feature of solid tumors. Hypoxic tumors are often resistant to conventional cancer therapies, and tumor hypoxia correlates with advanced stages of malignancy. Hypoxic tumors appear to be poorly differentiated. Increasing evidence suggests that hypoxia has the potential to inhibit tumor cell differentiation and thus plays a direct role in the maintenance of cancer stem cells. Studies have also shown that hypoxia blocks differentiation of mesenchymal stem/progenitor cells, a potential source of tumor-associated stromal cells. It is therefore likely that hypoxia may have a profound impact on the evolution of the tumor stromal microenvironment. These observations have led to the emergence of a novel paradigm for a role of hypoxia in facilitating tumor progression. Hypoxia may help create a microenvironment enriched in poorly differentiated tumor cells and undifferentiated stromal cells. Such an undifferentiated hypoxic microenvironment may provide essential cellular interactions and environmental signals for the preferential maintenance of cancer stem cells. This hypothesis suggests that effectively targeting hypoxic cancer stem cells is a key to successful tumor control. PMID:19519400

  1. Differentiation: A Strategic Response to Student Needs

    ERIC Educational Resources Information Center

    Hedrick, Kelly A.

    2012-01-01

    This article describes how the Virginia Beach schools have embraced differentiation as its new instructional philosophy, in part by adding it to teacher evaluation. The heart of guiding everyone in the district from novice to expert in the work focuses on these four essential questions: (1) Are we clear about what matters in curricula?; (2) Is the…

  2. Facilitating Engagement by Differentiating Independent Reading

    ERIC Educational Resources Information Center

    Kelley, Michelle J.; Clausen-Grace, Nicki

    2009-01-01

    The authors provide teachers with a rationale for engaging students in independent reading using a differentiated approach. By profiling types of readers, sharing observational tools, and offering teaching suggestions for each type of reader the authors give practical suggestions to facilitate reading engagement and make independent reading more…

  3. Cancer gene discovery using digital differential display.

    PubMed

    Scheurle, D; DeYoung, M P; Binninger, D M; Page, H; Jahanzeb, M; Narayanan, R

    2000-08-01

    The Cancer Gene Anatomy Project database of the National Cancer Institute has thousands of expressed sequences, both known and novel, in the form of expressed sequence tags (ESTs). These ESTs, derived from diverse normal and tumor cDNA libraries, offer an attractive starting point for cancer gene discovery. Using a data-mining tool called Digital Differential Display (DDD) from the Cancer Gene Anatomy Project database, ESTs from six different solid tumor types (breast, colon, lung, ovary, pancreas, and prostate) were analyzed for differential expression. An electronic expression profile and chromosomal map position of these hits were generated from the Unigene database. The hits were categorized into major classes of genes including ribosomal proteins, enzymes, cell surface molecules, secretory proteins, adhesion molecules, and immunoglobulins and were found to be differentially expressed in these tumorderived libraries. Genes known to be up-regulated in prostate, breast, and pancreatic carcinomas were discovered by DDD, demonstrating the utility of this technique. Two hundred known genes and 500 novel sequences were discovered to be differentially expressed in these select tumor-derived libraries. Test genes were validated for expression specificity by reverse transcription-PCR, providing a proof of concept for gene discovery by DDD. A comprehensive database of hits can be accessed at http:// www.fau.edu/cmbb/publications/cancergenes. htm. This solid tumor DDD database should facilitate target identification for cancer diagnostics and therapeutics.

  4. Three Ring Circus of Differentiated Instruction

    ERIC Educational Resources Information Center

    Scigliano, Deborah; Hipsky, Shellie

    2010-01-01

    The teacher as the classroom's ringleader, trying to fulfill the needs of all of her/his learners, at times, can seem like a three-ring circus. Just as enjoyment comes from the frenetic activity of the circus, benefits can stem from differentiating instruction for one's learners. These benefits include a sense of self-efficacy, increased content…

  5. Using Playing Cards to Differentiate Probability Interpretations

    ERIC Educational Resources Information Center

    López Puga, Jorge

    2014-01-01

    The aprioristic (classical, naïve and symmetric) and frequentist interpretations of probability are commonly known. Bayesian or subjective interpretation of probability is receiving increasing attention. This paper describes an activity to help students differentiate between the three types of probability interpretations.

  6. Maximizing Student Success with Differentiated Learning

    ERIC Educational Resources Information Center

    Morgan, Hani

    2014-01-01

    Students tend to comprehend little and lose focus of classroom instruction when their teachers fail to use instructional strategies that match students' learning styles. Differentiated instruction can alleviate or eliminate this disengagement. This article describes a case involving a child having difficulty learning and shows how…

  7. Differentiated Contracts: Giving Students Freedom to Learn

    ERIC Educational Resources Information Center

    Duncan, Tisha Admire

    2013-01-01

    Using Tomlinson's (2004) framework, the post-secondary classroom can be transformed into a community of learners where different avenues are provided for effectively acquiring content, processing ideas, and developing products. This article explores how instructors can differentiate instruction in teacher-education methods courses by…

  8. Comment on Differentiating Paranoid From Nonparanoid Schizophrenics

    ERIC Educational Resources Information Center

    Calhoun, James F.

    1971-01-01

    Three methods of differentiating paranoid from nonparanoid schizophrenics were compared using 97 males from a Veterans Administration hospital. Official hospital diagnosis and behavior ratings were found to be significantly correlated, while self-report correlated with neither of the other two techniques. Implications for research are briefly…

  9. Determinants of Fertility Differential in Korea.

    ERIC Educational Resources Information Center

    Shin, Eui Hang; And Others

    1981-01-01

    Analyzes the causal relationships of the fertility differentials of 2200 married women in a small Korean town. Notes the effect on fertility of socioeconomic status, age at first marriage, family background, and various family planning strategies (contraception, abortion). Discusses a process model on fertility. (Author/SB)

  10. Sampling Adequacy and the Semantic Differential.

    ERIC Educational Resources Information Center

    Dziuban, Charles D.; Shirkey, Edwin C.

    The Kaiser Measures of Sampling Adequacy (MSA) were derived for a typical six-concept Semantic Differential. The overall indices indicated that both concept and total correlation matrices would lead to comparable decisions regarding the psychometric quality of the sample data sets. The individual MSA's, however, revealed considerable variability…

  11. Differentiation in College Effective Reading Programs.

    ERIC Educational Resources Information Center

    Pellettieri, A. J.

    The varied reading deficiencies of college students of several backgrounds and ability levels are described to illustrate the need for differentiation in effective reading instruction for college students. It is contended that the fact that many good students are slow and poor readers is continually overlooked in reading instruction. Data from…

  12. Differentiated Instruction, Professional Development, and Teacher Efficacy

    ERIC Educational Resources Information Center

    Dixon, Felicia A.; Yssel, Nina; McConnell, John M.; Hardin, Travis

    2014-01-01

    Teachers often struggle to provide all students access to specific learning activities that work best for them--and what works best for some students will not work for others. Differentiating instruction makes sense because it offers different paths to understanding content, process, and products, considering what is appropriate given a…

  13. Civil helicopter flight operations using differential GPS

    NASA Technical Reports Server (NTRS)

    Edwards, F. G.; Loomis, P. V. W.

    1985-01-01

    The results of NASA flight trials of a dual-receiver differential global positioning system (DGPS) for civilian helicopter navigation applications, are presented. The three principal components of the DGPS system are described, including the GPS ground-reference system, a range tracking system, and an on-board sequential GPS receiver. The ground-based receiver in the DGPS operates at a known fixed location and receives C/A code signals from NAVSTAR satellites. System bias errors in the ground receiver are subtracted from the airborne solution for the navigational fix. Calculations of the differential bias error are carried out using an on-board PDP-11/34 M research computer. The ground-reference differential corrections for satellites are given in a table. It is shown that the differential correction signal of the DGPS contains only a small (0.1 rad/sec) high-frequency component which can be attributed to system error. A schematic diagram of the DGPS postflight data processing routine is provided.

  14. Differentiated Learning: From Policy to Classroom

    ERIC Educational Resources Information Center

    Mills, Martin; Monk, Sue; Keddie, Amanda; Renshaw, Peter; Christie, Pam; Geelan, David; Gowlett, Christina

    2014-01-01

    This paper explores the impact of a Teaching and Learning Audit of all government schools in Queensland, Australia. This audit has a concern with the extent to which schools "differentiate classroom learning". We note that in England, since September 2012, one of the standards that teachers have been expected to demonstrate is an ability…

  15. [Differential diagnosis of secondary arterial hypertension].

    PubMed

    Ruilope, L M

    1990-01-01

    The adequate performance of the differential diagnosis will permit us to classify any increase in blood pressure as due to primary or secondary causes. The data obtained in the clinical history and physical examination as well as those obtained through the minimal laboratory tests to be performed are the clues to identify secondary causes of arterial hypertension.

  16. Differential Response: Response to Hughes and Colleagues

    ERIC Educational Resources Information Center

    Samuels, Bryan; Brown, Brett Vaughn

    2013-01-01

    In their critique of differential response (DR), Hughes and colleagues raise a number of important issues that are central to broader efforts at the Administration on Children, Youth, and Families (ACYF) including the need for greater reliance on evidence-based practice in child welfare, more rigorous evaluation methodologies, and a robust set of…

  17. Invited Commentary on "Issues in Differential Response"

    ERIC Educational Resources Information Center

    Vaughan-Eden, Viola; Vandervort, Frank E.

    2013-01-01

    Ronald Hughes and his colleagues have written a groundbreaking article on child welfare's use of differential response. Their research addresses the matter from a "lessons learned" and "ways to improve" approach. Our comments focused on three key issues: (1) the importance of evidence-based practice; (2) the recognition…

  18. Goldilocks/Baby Bear Approach to Differentiation

    ERIC Educational Resources Information Center

    Oliver, Cindy Lovell

    2007-01-01

    The teacher's of America's one-room schoolhouses long ago mastered the concept of differentiation. Small class sizes were the norm, including children of all ages. Older, or more advanced students, helped others understand their lessons. Students move on to more difficult work as they were ready. Skipping grades was not uncommon. As the population…

  19. Unisexual cucumber flowers, sex and sex differentiation.

    PubMed

    Bai, Shu-Nong; Xu, Zhi-Hong

    2013-01-01

    Sex is a universal phenomenon in the world of eukaryotes. Attempts have been made to understand regulatory mechanisms for plant sex determination by investigating unisexual flowers. The cucumber plant is one of the model systems for studying how sex determination is regulated by phytohormones. A systematic investigation of the development of unisexual cucumber flowers is summarized here, and it is suggested that the mechanism of the unisexual flower can help us to understand how the process leading to one type of gametogenesis is prevented. Based on these findings, we concluded that the unisexual cucumber flowers is not an issue of sex differentiation, but instead a mechanism for avoiding self-pollination. Sex differentiation is essentially the divergent point(s) leading to heterogametogenesis. On the basis of analyses of sex differentiation in unicellular organisms and animals as well as the core process of plant life cycle, a concept of "sexual reproduction cycle" is proposed for understanding the essential role of sex and a "progressive model" for future investigations of sex differentiation in plants.

  20. Responding to "Issues in Differential Response"

    ERIC Educational Resources Information Center

    Perry, Robin Ernest

    2013-01-01

    Hughes, Rycus, Saunders-Adams, Hughes, and Hughes's article represents an important effort to critically examine the foundation of thought and empirical evidence associated with the rise in prominence of differential response (DR) within child welfare systems throughout the United States. The insights and criticisms offered are an important…

  1. Content, Process, and Product: Modeling Differentiated Instruction

    ERIC Educational Resources Information Center

    Taylor, Barbara Kline

    2015-01-01

    Modeling differentiated instruction is one way to demonstrate how educators can incorporate instructional strategies to address students' needs, interests, and learning styles. This article discusses how secondary teacher candidates learn to focus on content--the "what" of instruction; process--the "how" of instruction;…

  2. Applications of Differential Geometry to Cartography

    ERIC Educational Resources Information Center

    Benitez, Julio; Thome, Nestor

    2004-01-01

    This work introduces an application of differential geometry to cartography. The mathematical aspects of some geographical projections of Earth surface are revealed together with some of its more important properties. An important problem since the discovery of the 'spherical' form of the Earth is how to compose a reliable map of the surface of…

  3. Bobbing for Widgets: Compensating Wage Differentials

    ERIC Educational Resources Information Center

    Eckel, Catherine; McInnes, Melayne Morgan; Solnick, Sara; Ensminger, Jean; Fryer, Roland; Heiner, Ronald; Samms, Gavin; Sieberg, Katri; Wilson, Rick

    2005-01-01

    The authors describe a classroom game that introduces the concept of compensating wage differentials by allowing students to negotiate over the assignment of jobs and wages. Two jobs are designed so that neither job requires special skills, but one is significantly more unpleasant than the other. By varying the job titles and duties, students can…

  4. Residency Classification of Students for Tuition Differential.

    ERIC Educational Resources Information Center

    Vestal, Allan D.

    The classification of students in state-owned institutions of higher learning for the purpose of tuition differential involves a number of different legal problems. In an effort to shed some light on the problems involved, five questions are posed and answers attempted. These questions are: (1) Is it constitutionally permissible for a state to…

  5. Exotic differentiable structures and general relativity

    NASA Astrophysics Data System (ADS)

    Brans, Carl H.; Randall, Duane

    1993-02-01

    We review recent developments in differential topology with special concern for their possible significance to physical theories, especially general relativity. In particular we are concerned here with the discovery of the existence of non-standard (“fake” or “exotic”) differentiable structures on topologically simple manifolds such asS 7, ℝ4 andS 3 X ℝ1. Because of the technical difficulties involved in the smooth case, we begin with an easily understood toy example looking at the role which the choice of complex structures plays in the formulation of two-dimensional vacuum electrostatics. We then briefly review the mathematical formalisms involved with differentiable structures on topological manifolds, diffeomorphisms and their significance for physics. We summarize the important work of Milnor, Freedman, Donaldson, and others in developing exotic differentiable structures on well known topological manifolds. Finally, we discuss some of the geometric implications of these results and propose some conjectures on possible physical implications of these new manifolds which have never before been considered as physical models.

  6. High-pressure differential scanning microcalorimeter.

    PubMed

    Senin, A A; Dzhavadov, L N; Potekhin, S A

    2016-03-01

    A differential scanning microcalorimeter for studying thermotropic conformational transitions of biopolymers at high pressure has been designed. The calorimeter allows taking measurements of partial heat capacity of biopolymer solutions vs. temperature at pressures up to 3000 atm. The principles of operation of the device, methods of its calibration, as well as possible applications are discussed. PMID:27036806

  7. Use of labeled primers for differential display

    SciTech Connect

    Paunesku, T.; Woloschak, G.E.

    1995-02-01

    The differential display of eukaryotic cDNAs using PCR allows for determination of mRNA species differentially expressed when comparing two similar cell populations. This procedure uses a (T){sub 12}XY oligonucleotide as the 3 ft primer and an arbitrary 8-10-mer as the 5 ft primer. Labeling occurs by inclusion of {alpha}[{sup 33}P]-dATP in the PCR reaction. Two artifacts caused by this approach are (1) random printing from dT present from affinity purification of PolyA+RNA and (2) hybridization of the arbitrary primer to template target sequences on both cDNA strands. In this work, we have developed an approach for both eliminating smearing and identifying nonspecific bands on sequencing gels. By separately using 5 ft-end-labeled (T){sub 12}XY and arbitrary primers to label bands and comparing two differential display patterns rather than including labeled nucleotides in the PCR reaction itself, we can detect only those products incorporating the M{sub 12}XY primer on the 3 ft ends and the arbitrary primer on 5 ft ends. Those bands that are generated randomly in the PCR reaction are readily detectable and can be ignored. If on the other hand, one is interested only in a diagnostic banding pattern for differential display, benefit can be derived from the simplicity of the pattern obtained when labeled (T){sub 12}XY is used.

  8. Changes in Differentiation-Relatedness During Psychoanalysis.

    PubMed

    Calamaras, Martha R; Reviere, Susan L; Gallagher, Kathryn E; Kaslow, Nadine J

    2016-01-01

    This study sought to determine (a) if the Differentiation-Relatedness Scale of Self and Object Representations (D-RS), a coding model used with the Object Relations Inventory (Blatt, Wein, Chevron, & Quinlan, 1979 ) could be reliably applied to transcripts of psychoanalyses, and (b) if levels of differentiation-relatedness improve over the course of psychoanalysis. Participants were 4 creative writers who underwent psychoanalysis as part of a longitudinal research project focused on the processes and outcomes of psychoanalysis. Transcripts from the beginning and termination phases of psychoanalysis were coded by 2 independent raters for global, low, and high levels of self and other differentiation-relatedness and compared. There was good interrater agreement, suggesting that, like other forms of narrative material, psychoanalysis transcripts can be reliably rated for levels of object relations. Analysands showed an increase in global levels of differentiation-relatedness from a predominance of emergent ambivalent constancy (M = 6.2) at the beginning of analysis to consolidated, constant representations of self and other (M = 7.5) at the end of analysis. These preliminary findings contribute significantly to the empirical literature with regard to the measurement of self and object representations and change in these representations over the course of psychoanalysis.

  9. Stochastic Differential Games with Asymmetric Information

    SciTech Connect

    Cardaliaguet, Pierre Rainer, Catherine

    2009-02-15

    We investigate a two-player zero-sum stochastic differential game in which the players have an asymmetric information on the random payoff. We prove that the game has a value and characterize this value in terms of dual viscosity solutions of some second order Hamilton-Jacobi equation.

  10. Sex Differentiation and Sex Identification: Cultural Considerations.

    ERIC Educational Resources Information Center

    Bolling, John; Hassibi, Mahin

    The present study is part of a larger research project which is concerned with the cultural dimensions of interpretations of sexual differentiation in children's drawings. The basic assumption of this study is that the first figure drawn when a child is asked to draw a person is significantly related to, but does not necessarily establish, the…

  11. A Differential Magnetic Circuit for Teaching Purposes

    ERIC Educational Resources Information Center

    Kraftmakher, Yaakov

    2010-01-01

    A differential magnetic circuit (magnetic bridge) is described. The circuit separates the magnetic field sensor and the sample under study. A Hall probe serves as the sensor. The signal from the sensor can be enhanced by concentrating the magnetic flux. The magnetic bridge works even with dc magnetic fields. The device is used for displaying…

  12. Neuronal growth and differentiation on biodegradable membranes.

    PubMed

    Morelli, Sabrina; Piscioneri, Antonella; Messina, Antonietta; Salerno, Simona; Al-Fageeh, Mohamed B; Drioli, Enrico; De Bartolo, Loredana

    2015-02-01

    Semipermeable polymeric membranes with appropriate morphological, physicochemical and transport properties are relevant to inducing neural regeneration. We developed novel biodegradable membranes to support neuronal differentiation. In particular, we developed chitosan, polycaprolactone and polyurethane flat membranes and a biosynthetic blend between polycaprolactone and polyurethane by phase-inversion techniques. The biodegradable membranes were characterized in order to evaluate their morphological, physicochemical, mechanical and degradation properties. We investigated the efficacy of these different membranes to promote the adhesion and differentiation of neuronal cells. We employed as model cell system the human neuroblastoma cell line SHSY5Y, which is a well-established system for studying neuronal differentiation. The investigation of viability and specific neuronal marker expression allowed assessment that the correct neuronal differentiation and the formation of neuronal network had taken place in vitro in the cells seeded on different biodegradable membranes. Overall, this study provides evidence that neural cell responses depend on the nature of the biodegradable polymer used to form the membranes, as well as on the dissolution, hydrophilic and, above all, mechanical membrane properties. PCL-PU membranes exhibit mechanical properties that improve neurite outgrowth and the expression of specific neuronal markers.

  13. Earth fissures and localized differential subsidence

    USGS Publications Warehouse

    Holzer, Thomas L.; Pampeyan, Earl Haig

    1979-01-01

    Long tension cracks caused by declines of ground-water level at four sites in Arizona, California, and Nevada occur at points of maximum, convex-upward curvature in subsidence profiles based on relevelings of closely-spaced bench marks aligned perpendicular to the cracks. We conclude the cracks are caused by horizontal strains associated with the differential subsidence.

  14. Mechanisms of androgen induction of sebocyte differentiation.

    PubMed

    Rosenfield, R L; Deplewski, D; Kentsis, A; Ciletti, N

    1998-01-01

    It has been difficult to induce the expected sebocyte differentiation in vitro with dihydrotestosterone (DHT). We reasoned that our culture system lacks differentiating factors, and peroxisome proliferator-activated receptors (PPARs) were the prime candidates. We tested PPAR activators informative about diverse PPAR subtypes, with and without DHT (10(-6) M): BRL-49653 (10(-6) M, PPAR-gamma), WY-14643 (10(-6) M, PPAR-alpha), and linoleic acid (LIN, 10(-4) M, PPAR-delta). Treatments were added in serum-free medium to cultures of rat preputial sebocytes. Control, DHT, BRL and BRL + DHT treatments caused 11, 25, 66 and 80%, respectively, of preputial cell colonies to differentiate into lipid-forming colonies (LFCs) (p < 0.001). WY induced 20% and LIN over 95% LFC formation. PPAR-gamma mRNA was identified in preputial sebocytes by the RNase protection assay. These data suggest that differentiation of sebocytes is transduced by PPARs and have implications for the development of new treatments for acne. PMID:9557223

  15. Differential diagnosis of severe cutaneous drug eruptions.

    PubMed

    Bachot, Nicolas; Roujeau, Jean-Claude

    2003-01-01

    Adverse cutaneous reactions to drugs are frequent, mostly secondary to antibacterials, however, serious adverse cutaneous reactions are infrequent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are a spectrum of the same disease. They are the more severe drug eruptions, with a mortality around 30% for TEN. The confusion between erythema multiforme major and SJS means that erythema multiforme major is the main differential diagnosis. Skin disorders involving desquamation, in particular after pustulosis, are also common differential diagnoses. Mechanical or autoimmune blistering are also potential misdiagnoses of TEN/SJS. Hypersensitivity Syndrome (HSS) or Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) is a severe cutaneous drug reaction with often a long duration of eruption and serious other organ involvement. Exfoliative dermatitis, whether caused by psoriasis, dermatitis or lymphoma, can be thought of as a differential diagnosis of DRESS/HSS. Angio-immunoblastic lymphadenopathy, viral eruption and vasculitis are other differential diagnoses of DRESS/HSS. Prompt recognition of a severe drug reaction and withdrawal of the culprit drug is often the most important therapeutic action. Alternatively, a delay in starting a specific treatment for a disease misdiagnosed as a drug eruption could be deleterious.

  16. Canonical coordinates for partial differential equations

    NASA Technical Reports Server (NTRS)

    Hunt, L. R.; Villarreal, Ramiro

    1988-01-01

    Necessary and sufficient conditions are found under which operators of the form Sigma (m, j=1) x (2) sub j + X sub O can be made constant coefficient. In addition, necessary and sufficient conditions are derived which classify those linear partial differential operators that can be moved to the Kolmogorov type.

  17. Canonical coordinates for partial differential equations

    NASA Technical Reports Server (NTRS)

    Hunt, L. R.; Villarreal, Ramiro

    1987-01-01

    Necessary and sufficient conditions are found under which operators of the form Sigma(m, j=1) X(2)sub j + X sub 0 can be made constant coefficient. In addition, necessary and sufficient conditions are derived which classify those linear partial differential operators that can be moved to the Kolmogorov type.

  18. Who Wants To Differentiate Instruction? We Did...

    ERIC Educational Resources Information Center

    Fahey, John A.

    2000-01-01

    In its valiant differentiation and detracking efforts, a Virginia high school hoped to assist all students in mastering state standards and enrich, excite, and challenge high-ability students via learning contracts and advanced material feeding their interests. However, disgruntled parents managed to reinstate the tracking system. (MLH)

  19. The increasingly complex regulation of adipocyte differentiation

    PubMed Central

    Poulos, Sylvia P; Dodson, Michael V; Culver, Melinda F

    2015-01-01

    Adipose (AD) tissue development and function relies on the ability of adipocytes to proliferate and differentiate into lipid-containing cells that also have endocrine function. Research suggests that certain conditions can induce AD tissue stem cells to differentiate into various cell types and that the microenvironment of the cell, including the extracellular matrix (ECM), is essential in maintaining cell and tissue function. This review provides an overview of factors involved in the proliferation and differentiation of adipocytes. A brief review of the numerous factors that influence PPARγ, the transcription factor thought to be the master regulator of adipocyte differentiation, provides context of established pathways that regulate adipogenesis. Thought provoking findings from research with hypoxia that is supported by earlier research that vascular development is related to adipogenesis are reviewed. Finally, our understanding of the critical role of the ECM and environment in adipogenesis is discussed and compared with studies that suggest that adipocytes may dedifferentiate and can convert into other cell types. PMID:26645953

  20. Differential Prediction Generalization in College Admissions Testing

    ERIC Educational Resources Information Center

    Aguinis, Herman; Culpepper, Steven A.; Pierce, Charles A.

    2016-01-01

    We introduce the concept of "differential prediction generalization" in the context of college admissions testing. Specifically, we assess the extent to which predicted first-year college grade point average (GPA) based on high-school grade point average (HSGPA) and SAT scores depends on a student's ethnicity and gender and whether this…

  1. Using Blogs to Improve Differentiated Instruction

    ERIC Educational Resources Information Center

    Colombo, Michaela W.; Colombo, Paul D.

    2007-01-01

    The authors discuss how the instructional impact of science teachers can be extended by using blogs, a technology popular among students that allows teachers to differentiate their instruction for students with diverse needs. Software now makes it easy for teachers to establish class blogs, Web sites that contain text, audio, and video postings on…

  2. Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation

    PubMed Central

    Kwon, Minsuk; Kim, Jin-Man; Lee, Kyunghee; Park, So-Young; Lim, Hyun-Sook; Kim, Taesoo; Jeong, Daewon

    2016-01-01

    Osteoclast progenitors undergo cell cycle arrest before differentiation into osteoclasts, induced by exposure to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The role of such cell cycle arrest in osteoclast differentiation has remained unclear, however. We here examined the effect of synchronized cell cycle arrest on osteoclast formation. Osteoclast progenitors deprived of M-CSF in culture adopted a uniform morphology and exhibited cell cycle arrest at the G0–G1 phase in association with both down-regulation of cyclins A and D1 as well as up-regulation of the cyclin-dependent kinase inhibitor p27Kip1. Such M-CSF deprivation also promoted the differentiation of osteoclast progenitors into multinucleated osteoclasts expressing high levels of osteoclast marker proteins such as NFATc1, c-Fos, Atp6v0d2, cathepsin K, and integrin β3 on subsequent exposure to M-CSF and RANKL. Our results suggest that synchronized arrest and reprogramming of osteoclast progenitors renders them poised to respond to inducers of osteoclast formation. Further characterization of such effects may facilitate induction of the differentiation of heterogeneous and multipotent cells into desired cell lineages. PMID:27517906

  3. Extending the Study of Gender Differentiation.

    ERIC Educational Resources Information Center

    Liben, Lynn S.; Bigler, Rebecca S.

    2002-01-01

    Responds to concerns that individual items included as stereotypes in the Occupation Activity Trait Scales (children's and adult's versions) are not highly stereotyped. Discusses future directions for research, noting that a developmental approach is critical to understanding gender differentiation establishment and that it is also important to…

  4. Differential thermal analysis of lunar soil simulant

    NASA Technical Reports Server (NTRS)

    Tucker, D.; Setzer, A.

    1991-01-01

    Differential thermal analysis of a lunar soil simulant, 'Minnesota Lunar Simulant-1' (MLS-1) was performed. The MLS-1 was tested in as-received form (in glass form) and with another silica. The silica addition was seen to depress nucleation events which lead to a better glass former.

  5. Mapping a Route toward Differentiated Instruction.

    ERIC Educational Resources Information Center

    Tomlinson, Carol Ann

    1999-01-01

    Although students may learn in many ways, the essential skills and content they learn can remain steady. As demonstrated by three teaching approaches to the study of ancient Rome, students can take different roads to the same destination. Successful differentiation is rooted in student engagement and student understanding. (MLH)

  6. Differentiability of correlations in realistic quantum mechanics

    SciTech Connect

    Cabrera, Alejandro; Faria, Edson de; Pujals, Enrique; Tresser, Charles

    2015-09-15

    We prove a version of Bell’s theorem in which the locality assumption is weakened. We start by assuming theoretical quantum mechanics and weak forms of relativistic causality and of realism (essentially the fact that observable values are well defined independently of whether or not they are measured). Under these hypotheses, we show that only one of the correlation functions that can be formulated in the framework of the usual Bell theorem is unknown. We prove that this unknown function must be differentiable at certain angular configuration points that include the origin. We also prove that, if this correlation is assumed to be twice differentiable at the origin, then we arrive at a version of Bell’s theorem. On the one hand, we are showing that any realistic theory of quantum mechanics which incorporates the kinematic aspects of relativity must lead to this type of rough correlation function that is once but not twice differentiable. On the other hand, this study brings us a single degree of differentiability away from a relativistic von Neumann no hidden variables theorem.

  7. Detection of explosives by differential hyperspectral imaging

    NASA Astrophysics Data System (ADS)

    Dubroca, Thierry; Brown, Gregory; Hummel, Rolf E.

    2014-02-01

    Our team has pioneered an explosives detection technique based on hyperspectral imaging of surfaces. Briefly, differential reflectometry (DR) shines ultraviolet (UV) and blue light on two close-by areas on a surface (for example, a piece of luggage on a moving conveyer belt). Upon reflection, the light is collected with a spectrometer combined with a charge coupled device (CCD) camera. A computer processes the data and produces in turn differential reflection spectra taken from these two adjacent areas on the surface. This differential technique is highly sensitive and provides spectroscopic data of materials, particularly of explosives. As an example, 2,4,6-trinitrotoluene displays strong and distinct features in differential reflectograms near 420 and 250 nm, that is, in the near-UV region. Similar, but distinctly different features are observed for other explosives. Finally, a custom algorithm classifies the collected spectral data and outputs an acoustic signal if a threat is detected. This paper presents the complete DR hyperspectral imager which we have designed and built from the hardware to the software, complete with an analysis of the device specifications.

  8. Parallel Algorithm Solves Coupled Differential Equations

    NASA Technical Reports Server (NTRS)

    Hayashi, A.

    1987-01-01

    Numerical methods adapted to concurrent processing. Algorithm solves set of coupled partial differential equations by numerical integration. Adapted to run on hypercube computer, algorithm separates problem into smaller problems solved concurrently. Increase in computing speed with concurrent processing over that achievable with conventional sequential processing appreciable, especially for large problems.

  9. The effect of dehydroleucodine in adipocyte differentiation.

    PubMed Central

    Galvis, Adriana; Marcano, Adriana; Stefancin, Chad; Villaverde, Nicole; Priestap, Horacio A.; Tonn, Carlos E.; Lopez, Luis A.; Barbieri, Manuel A.

    2012-01-01

    Dehydroleucodine (DhL) is a sesquiterpene lactone of the guaianolide group with gastric citoprotective activity. Recent studies have also demonstrated that DhL inhibits the proliferation of vascular smooth muscle cells. In this study we examined the effect of DhL in the differentiation 3T3-L1 preadipocytes. The addition of DhL significantly inhibited the differentiation 3T3-L1 preadipocytes along with significant decrease in the accumulation of lipid content by a dramatic down regulation of the expression of adipogenic-specific transcriptional factors PPARγ and C-EBPα. However, phosphorylation of AMPKα, Erk1/2 and Akt1 was not inhibited by DhL treatment. Interestingly, we also found that 11,13-dihydro-dehydroleucodine, a derivative of DhL with inactivated α-methylene-γ-lactone function, also inhibited the differentiation 3T3-L1 preadipocytes. Taken together, these data suggest DhL has an important inhibitory effect in cellular pathways regulating adipocyte differentiation by modulating the PPARγ expression, which is known to play a pivotal role during adipogenesis. PMID:21963454

  10. Real and Artificial Differential Item Functioning

    ERIC Educational Resources Information Center

    Andrich, David; Hagquist, Curt

    2012-01-01

    The literature in modern test theory on procedures for identifying items with differential item functioning (DIF) among two groups of persons includes the Mantel-Haenszel (MH) procedure. Generally, it is not recognized explicitly that if there is real DIF in some items which favor one group, then as an artifact of this procedure, artificial DIF…

  11. Ramsay-Curve Differential Item Functioning

    ERIC Educational Resources Information Center

    Woods, Carol M.

    2011-01-01

    Differential item functioning (DIF) occurs when an item on a test, questionnaire, or interview has different measurement properties for one group of people versus another, irrespective of true group-mean differences on the constructs being measured. This article is focused on item response theory based likelihood ratio testing for DIF (IRT-LR or…

  12. Differential Diagnosis of Stuttering for Forensic Purposes

    ERIC Educational Resources Information Center

    Seery, Carol Hubbard

    2005-01-01

    Purpose: This case study demonstrates the application of an assessment protocol for differential diagnosis of psychogenic stuttering, neurogenic stuttering, developmental stuttering, and malingering. Method: A male in his late 30s, accused of armed robbery, was evaluated for stuttering at the request of his defense attorney. The speech assessment…

  13. BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL TROPHOBLAST DIFFERENTIATION

    EPA Science Inventory

    BROMODICHLOROMETHANE INHIBITS HUMAN PLACENTAL
    TROPHOBLAST DIFFERENTIATION
    Jiangang Chen, Twanda L. Thirkill, Peter N. Lohstroh, Susan R. Bielmeier, Michael
    G. Narotsky, Deborah S. Best, Randy A. Harrison, Kala Natarajan, Rex A. Pegram,
    Bill L. Lasley, and Gordon C. Do...

  14. Sociodemographic Differentials in Mate Selection Preferences.

    ERIC Educational Resources Information Center

    South, Scott J.

    1991-01-01

    Used data from over 2,000 respondents in National Survey of Families and Households to examine sociodemographic differentials in stated willingness of individuals to marry persons with various social, economic, and demographic characteristics. Men placed higher value on physical attractiveness and youth; women placed value on earnings and…

  15. Grade Awarding Judgments in Differentiated Examinations.

    ERIC Educational Resources Information Center

    Good, F. J.; Cresswell, M. J.

    1988-01-01

    Investigates the consistency of the standards applied by graders on the General Certificate of Secondary Education examinations in the United Kingdom and the application of these standards to define comparable levels of achievement in differentiated examinations. Suggests that the need for comparability based on the candidates' responses be taken…

  16. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation

    PubMed Central

    Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi; Patel, Vyomesh; Fukumoto, Satoshi; Yamada, Yoshihiko

    2014-01-01

    ABSTRACT The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development. PMID:25344255

  17. Epiprofin orchestrates epidermal keratinocyte proliferation and differentiation.

    PubMed

    Nakamura, Takashi; Yoshitomi, Yasuo; Sakai, Kiyoshi; Patel, Vyomesh; Fukumoto, Satoshi; Yamada, Yoshihiko

    2014-12-15

    The basal layer of the epidermis contains stem cells and transit amplifying cells that rapidly proliferate and differentiate further into the upper layers of the epidermis. A number of molecules have been identified as regulators of this process, including p63 (also known as tumor protein 63) and Notch1. However, little is known about the mechanisms that regulate the transitions from stem cell to proliferating or differentiating transit amplifying cell. Here, we demonstrate that epiprofin (Epfn, also known as Sp6) plays crucial distinct roles in these transition stages as a cell cycle regulator and a transcription factor. Epfn knockout mice have a thickened epidermis, in which p63-expressing basal cells form multiple layers owing to the accumulation of premature transit amplifying cells with reduced proliferation and a reduction in the number of differentiating keratinocytes expressing Notch1. We found that low levels of Epfn expression increased the proliferation of human immortalized keratinocyte (HaCaT) cells by increasing EGF responsiveness and superphosphorylation of Rb. By contrast, high levels of Epfn expression promoted cell cycle exit and differentiation, by reducing E2F transactivation and inducing Notch1 expression. Our findings identify multiple novel functions of Epfn in epidermal development. PMID:25344255

  18. Induced differentiation inhibits sphere formation in neuroblastoma.

    PubMed

    Craig, Brian T; Rellinger, Eric J; Alvarez, Alexandra L; Dusek, Haley L; Qiao, Jingbo; Chung, Dai H

    2016-08-19

    Neuroblastoma arises from the neural crest, the precursor cells of the sympathoadrenal axis, and differentiation status is a key prognostic factor used for clinical risk group stratification and treatment strategies. Neuroblastoma tumor-initiating cells have been successfully isolated from patient tumor samples and bone marrow using sphere culture, which is well established to promote growth of neural crest stem cells. However, accurate quantification of sphere-forming frequency of commonly used neuroblastoma cell lines has not been reported. Here, we show that MYCN-amplified neuroblastoma cell lines form spheres more frequently than non-MYCN-amplified cell lines. We also show that sphere formation is directly sensitive to cellular differentiation status. 13-cis-retinoic acid is a clinically used differentiating agent that induces a neuronal phenotype in neuroblastoma cells. Induced differentiation nearly completely blocked sphere formation. Furthermore, sphere formation was specifically FGF-responsive and did not respond to increasing doses of EGF. Taken together, these data suggest that sphere formation is an accurate method of quantifying the stemness phenotype in neuroblastoma. PMID:27297102

  19. Infrared differential absorption for atmospheric pollutant detection

    NASA Technical Reports Server (NTRS)

    Byer, R. L.

    1974-01-01

    Progress made in the generation of tunable infrared radiation and its application to remote pollutant detection by the differential absorption method are summarized. It is recognized that future remote pollutant measurements depended critically on the availability of high energy tunable transmitters. Futhermore, due to eye safety requirements, the transmitted frequency must lie in the 1.4 micron to 13 micron infrared spectral range.

  20. [Myoepithelial differentiation markers in salivary gland neoplasia].

    PubMed

    Scarpellini, F; Marucci, G; Foschini, M P

    2001-12-01

    Salivary gland tumors frequently present myoepithelial cell differentiation that is not always easily identified on routinely stained sections. Recently novel markers of myoepithelium have been studied, such as calponin (CALP), caldesmon (CALD), and smooth muscle myosin heavy chain. These markers, together with smooth muscle actin may be useful tools for identifying myoepithelial cells. We immunohistochemically studied a series of 23 benign and malignant salivary gland tumors using antibodies to these four markers. The tumors were classified as follows: pleomorphic adenoma (n = 8), basal cell adenoma (n = 3), myoepithelioma with plasmacytoid cells (n = 2), epithelial-myoepithelial cell carcinoma (n = 6) and adenoid cystic carcinoma (n = 4). All tumors were positive for at least one of the four markers. CALP and smooth muscle actin were the markers more frequently expressed. Positivity was mostly located in the myoepithelial cells that constitute the external layer of the glandular or tubular neoplastic structures. In poorly differentiated epithelial myoepithelial carcinomas, composed of solid sheets of neoplastic cells and sometimes of clear cells, immunohistochemical staining for myoepithelial markers evidenced rudimentary glandular structures. CALP and smooth muscle actin were positive in the two cases of myoepithelioma with plasmacytoid cells. In conclusion, the combined staining with four markers helps to disclose myoepithelial cell differentiation and can be a useful tool for the correct histopathological diagnosis of salivary gland tumors. Among the four markers studied, CALP and smooth muscle actin were the most useful to identify myoepithelial cell differentiation.

  1. A Multilevel Assessment of Differential Item Functioning.

    ERIC Educational Resources Information Center

    Shen, Linjun

    A multilevel approach was proposed for the assessment of differential item functioning and compared with the traditional logistic regression approach. Data from the Comprehensive Osteopathic Medical Licensing Examination for 2,300 freshman osteopathic medical students were analyzed. The multilevel approach used three-level hierarchical generalized…

  2. Synchronized Cell Cycle Arrest Promotes Osteoclast Differentiation.

    PubMed

    Kwon, Minsuk; Kim, Jin-Man; Lee, Kyunghee; Park, So-Young; Lim, Hyun-Sook; Kim, Taesoo; Jeong, Daewon

    2016-01-01

    Osteoclast progenitors undergo cell cycle arrest before differentiation into osteoclasts, induced by exposure to macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-κB ligand (RANKL). The role of such cell cycle arrest in osteoclast differentiation has remained unclear, however. We here examined the effect of synchronized cell cycle arrest on osteoclast formation. Osteoclast progenitors deprived of M-CSF in culture adopted a uniform morphology and exhibited cell cycle arrest at the G₀-G₁ phase in association with both down-regulation of cyclins A and D1 as well as up-regulation of the cyclin-dependent kinase inhibitor p27(Kip1). Such M-CSF deprivation also promoted the differentiation of osteoclast progenitors into multinucleated osteoclasts expressing high levels of osteoclast marker proteins such as NFATc1, c-Fos, Atp6v0d2, cathepsin K, and integrin β3 on subsequent exposure to M-CSF and RANKL. Our results suggest that synchronized arrest and reprogramming of osteoclast progenitors renders them poised to respond to inducers of osteoclast formation. Further characterization of such effects may facilitate induction of the differentiation of heterogeneous and multipotent cells into desired cell lineages. PMID:27517906

  3. Epilepsy-induced motility of differentiated neurons.

    PubMed

    Chai, Xuejun; Münzner, Gert; Zhao, Shanting; Tinnes, Stefanie; Kowalski, Janina; Häussler, Ute; Young, Christina; Haas, Carola A; Frotscher, Michael

    2014-08-01

    Neuronal ectopia, such as granule cell dispersion (GCD) in temporal lobe epilepsy (TLE), has been assumed to result from a migration defect during development. Indeed, recent studies reported that aberrant migration of neonatal-generated dentate granule cells (GCs) increased the risk to develop epilepsy later in life. On the contrary, in the present study, we show that fully differentiated GCs become motile following the induction of epileptiform activity, resulting in GCD. Hippocampal slice cultures from transgenic mice expressing green fluorescent protein in differentiated, but not in newly generated GCs, were incubated with the glutamate receptor agonist kainate (KA), which induced GC burst activity and GCD. Using real-time microscopy, we observed that KA-exposed, differentiated GCs translocated their cell bodies and changed their dendritic organization. As found in human TLE, KA application was associated with decreased expression of the extracellular matrix protein Reelin, particularly in hilar interneurons. Together these findings suggest that KA-induced motility of differentiated GCs contributes to the development of GCD and establish slice cultures as a model to study neuronal changes induced by epileptiform activity.

  4. Radial differential interior tomography and its image reconstruction with differentiated backprojection and projection onto convex sets

    SciTech Connect

    Tang, Shaojie; Tang, Xiangyang

    2013-09-15

    Purpose: Interior tomography has been recognized as one of the most effective approaches in computed tomography (CT) to reduce radiation dose rendered to patients. In this work, the authors propose and evaluate an imaging method of radial differential interior tomography.Methods: In interior tomography, an x-ray beam is collimated to only irradiate the region of interest (ROI) with suspected lesions while the surrounding area/volume of normal tissues/organs is spared. In the proposed imaging method of radial differential interior tomography, the outcome is a ROI image that has gone through a radial differential filtering. The image reconstruction algorithm for the radial differential interior tomography is kept in the fashion of differentiated backprojection and projection onto convex sets, but the required a priori knowledge in a small round area becomes zero and may be more readily available in practice.Results: Using the projection data simulated by computer and acquired by CT scanner, the authors evaluate and verify the performance of the proposed radial differential interior tomography method and its associated image reconstruction algorithm. The preliminary results show that the proposed imaging method can generate an image that is the radial differentiation of a conventional tomographic image and is robust over noise that inevitably exist in practice.Conclusions: It is believed that the proposed imaging method may find its utility in advanced clinical applications wherein a ROI-based image processing and analysis is required for lesion visualization, characterization, and diagnosis.

  5. Identification of differentially expressed non-coding RNAs in embryonic stem cell neural differentiation

    PubMed Central

    Skreka, Konstantinia; Schafferer, Simon; Nat, Irina-Roxanna; Zywicki, Marek; Salti, Ahmad; Apostolova, Galina; Griehl, Matthias; Rederstorff, Mathieu; Dechant, Georg; Hüttenhofer, Alexander

    2012-01-01

    Protein-coding genes, guiding differentiation of ES cells into neural cells, have extensively been studied in the past. However, for the class of ncRNAs only the involvement of some specific microRNAs (miRNAs) has been described. Thus, to characterize the entire small non-coding RNA (ncRNA) transcriptome, involved in the differentiation of mouse ES cells into neural cells, we have generated three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i.e. from pluripotent ES cells, neural progenitors and differentiated neural cells, respectively. By high-throughput sequencing and transcriptional profiling we identified several novel miRNAs to be involved in ES cell differentiation, as well as seven small nucleolar RNAs. In addition, expression of 7SL, 7SK and vault-2 RNAs was significantly up-regulated during ES cell differentiation. About half of ncRNA sequences from the three cDNA libraries mapped to intergenic or intragenic regions, designated as interRNAs and intraRNAs, respectively. Thereby, novel ncRNA candidates exhibited a predominant size of 18–30 nt, thus resembling miRNA species, but, with few exceptions, lacking canonical miRNA features. Additionally, these novel intraRNAs and interRNAs were not only found to be differentially expressed in stem-cell derivatives, but also in primary cultures of hippocampal neurons and astrocytes, strengthening their potential function in neural ES cell differentiation. PMID:22492625

  6. Identification of differentially expressed non-coding RNAs in embryonic stem cell neural differentiation.

    PubMed

    Skreka, Konstantinia; Schafferer, Simon; Nat, Irina-Roxanna; Zywicki, Marek; Salti, Ahmad; Apostolova, Galina; Griehl, Matthias; Rederstorff, Mathieu; Dechant, Georg; Hüttenhofer, Alexander

    2012-07-01

    Protein-coding genes, guiding differentiation of ES cells into neural cells, have extensively been studied in the past. However, for the class of ncRNAs only the involvement of some specific microRNAs (miRNAs) has been described. Thus, to characterize the entire small non-coding RNA (ncRNA) transcriptome, involved in the differentiation of mouse ES cells into neural cells, we have generated three specialized ribonucleo-protein particle (RNP)-derived cDNA libraries, i.e. from pluripotent ES cells, neural progenitors and differentiated neural cells, respectively. By high-throughput sequencing and transcriptional profiling we identified several novel miRNAs to be involved in ES cell differentiation, as well as seven small nucleolar RNAs. In addition, expression of 7SL, 7SK and vault-2 RNAs was significantly up-regulated during ES cell differentiation. About half of ncRNA sequences from the three cDNA libraries mapped to intergenic or intragenic regions, designated as interRNAs and intraRNAs, respectively. Thereby, novel ncRNA candidates exhibited a predominant size of 18-30 nt, thus resembling miRNA species, but, with few exceptions, lacking canonical miRNA features. Additionally, these novel intraRNAs and interRNAs were not only found to be differentially expressed in stem-cell derivatives, but also in primary cultures of hippocampal neurons and astrocytes, strengthening their potential function in neural ES cell differentiation. PMID:22492625

  7. Expression of Molecular Differentiation Markers Does Not Correlate with Histological Differentiation Grade in Intrahepatic Cholangiocarcinoma

    PubMed Central

    Demarez, Céline; Hubert, Catherine; Sempoux, Christine; Lemaigre, Frédéric P.

    2016-01-01

    The differentiation status of tumor cells, defined by histomorphological criteria, is a prognostic factor for survival of patients affected with intrahepatic cholangiocarcinoma (ICC). To strengthen the value of morphological differentiation criteria, we wished to correlate histopathological differentiation grade with expression of molecular biliary differentiation markers and of microRNAs previously shown to be dysregulated in ICC. We analysed a series of tumors that were histologically classified as well, moderately or poorly differentiated, and investigated the expression of cytokeratin 7, 19 and 903 (CK7, CK19, CK903), SRY-related HMG box transcription factors 4 and 9 (SOX4, SOX9), osteopontin (OPN), Hepatocyte Nuclear Factor-1 beta (HNF1β), Yes-associated protein (YAP), Epithelial cell adhesion molecule (EPCAM), Mucin 1 (MUC1) and N-cadherin (NCAD) by qRT-PCR and immunostaining, and of miR-31, miR-135b, miR-132, miR-200c, miR-221 and miR-222. Unexpectedly, except for subcellular location of SOX9 and OPN, no correlation was found between the expression levels of these molecular markers and histopathological differentiation grade. Therefore, our data point toward necessary caution when investigating the evolution and prognosis of ICC on the basis of cell differentiation criteria. PMID:27280413

  8. Regulation of mesenchymal stem cell differentiation and insulin secretion by differential expression of Pdx-1.

    PubMed

    Yuan, Huijuan; Liu, Hongmei; Tian, Rui; Li, Jie; Zhao, Zhigang

    2012-07-01

    In recent years, major effort has been made to differentiate embryonic stem cells, pancreatic ductal epithelial multipotent progenitor cells, and bone marrow stem cells into insulin secreting cells. Our previous work has also demonstrated the feasibility of inducing mesenchymal stem cells (MSC) to insulin secreting cells through overexpression of Pdx-1, a pancreas and islet-specific transcription factor that plays a major role in differentiation of islet β-cells during development (Yuan et al. in Mol Biol Rep 37:4023-4031, 2010). However, the levels of insulin secretion among these differentiated MSC were quite variable. The purpose of this study is to address the issue whether the insulin secretion level from the differentiated MSC lines are determined by the expression level of the Pdx-1 transgene. To do so, we have generated several differentiated MSC lines with stable transfection of the Pdx-1 gene. Using RT-PCR analysis and insulin secretion assay, we have analyzed Pdx-1 mRNA levels and insulin secretion from these stable MSC lines. Our results showed that Pdx-1 expression is absolutely required for the differentiation of MSC lines to insulin secreting cell lines. Furthermore, we demonstrated that the level of Pdx-1 expression is closely correlated with level of insulin mRNA and insulin secretion level in differentiated MSC stable cell lines. These findings suggest that the level of Pdx-1 expression plays a key role in induction of MSCs to insulin secreting cells.

  9. Effects of THAP11 on Erythroid Differentiation and Megakaryocytic Differentiation of K562 Cells

    PubMed Central

    Kong, Xiang-Zhen; Yin, Rong-Hua; Ning, Hong-Mei; Zheng, Wei-Wei; Dong, Xiao-Ming; Yang, Yang; Xu, Fei-Fei; Li, Jian-Jie; Zhan, Yi-Qun; Yu, Miao; Ge, Chang-Hui; Zhang, Jian-Hong; Chen, Hui; Li, Chang-Yan; Yang, Xiao-Ming

    2014-01-01

    Hematopoiesis is a complex process regulated by sets of transcription factors in a stage-specific and context-dependent manner. THAP11 is a transcription factor involved in cell growth, ES cell pluripotency, and embryogenesis. Here we showed that THAP11 was down-regulated during erythroid differentiation but up-regulated during megakaryocytic differentiation of cord blood CD34+ cells. Overexpression of THAP11 in K562 cells inhibited the erythroid differentiation induced by hemin with decreased numbers of benzidine-positive cells and decreased mRNA levels of α-globin (HBA) and glycophorin A (GPA), and knockdown of THAP11 enhanced the erythroid differentiation. Conversely, THAP11 overexpression accelerated the megakaryocytic differentiation induced by phorbol myristate acetate (PMA) with increased percentage of CD41+ cells, increased numbers of 4N cells, and elevated CD61 mRNA levels, and THAP11 knockdown attenuated the megakaryocytic differentiation. The expression levels of transcription factors such as c-Myc, c-Myb, GATA-2, and Fli1 were changed by THAP11 overexpression. In this way, our results suggested that THAP11 reversibly regulated erythroid and megakaryocytic differentiation. PMID:24637716

  10. Origin of igneous meteorites and differentiated asteroids

    NASA Astrophysics Data System (ADS)

    Scott, E.; Goldstein, J.; Asphaug, E.; Bottke, W.; Moskovitz, N.; Keil, K.

    2014-07-01

    Introduction: Igneously formed meteorites and asteroids provide major challenges to our understanding of the formation and evolution of the asteroid belt. The numbers and types of differentiated meteorites and non-chondritic asteroids appear to be incompatible with an origin by fragmentation of numerous Vesta-like bodies by hypervelocity impacts in the asteroid belt over 4 Gyr. We lack asteroids and achondrites from the olivine-rich mantles of the parent bodies of the 12 groups of iron meteorites and the ˜70 ungrouped irons, the 2 groups of pallasites and the 4--6 ungrouped pallasites. We lack mantle and core samples from the parent asteroids of the basaltic achondrites that do not come from Vesta, viz., angrites and the ungrouped eucrites like NWA 011 and Ibitira. How could core samples have been extracted from numerous differentiated bodies when Vesta's basaltic crust was preserved? Where is the missing Psyche family of differentiated asteroids including the complementary mantle and crustal asteroids [1]? Why are meteorites derived from far more differentiated parent bodies than chondritic parent bodies even though C and S class chondritic asteroids dominate the asteroid belt? New paradigm. Our studies of meteorites, impact modeling, and dynamical studies suggest a new paradigm in which differentiated asteroids accreted at 1--2 au less than 2 Myr after CAI formation [2]. They were rapidly melted by 26Al and disrupted by hit-and-run impacts [3] while still molten or semi-molten when planetary embryos were accreting. Metallic Fe-Ni bodies derived from core material cooled rapidly with little or no silicate insulation less than 4 Myr after CAI formation [4]. Fragments of differentiated planetesimals were subsequently tossed into the asteroid belt. Meteorite evidence for early disruption of differentiated asteroids. If iron meteorites were samples of Fe-Ni cores of bodies that cooled slowly inside silicate mantles over ˜50--100 Myr, irons from each core would have

  11. Differential network analysis in human cancer research.

    PubMed

    Gill, Ryan; Datta, Somnath; Datta, Susmita

    2014-01-01

    A complex disease like cancer is hardly caused by one gene or one protein singly. It is usually caused by the perturbation of the network formed by several genes or proteins. In the last decade several research teams have attempted to construct interaction maps of genes and proteins either experimentally or reverse engineer interaction maps using computational techniques. These networks were usually created under a certain condition such as an environmental condition, a particular disease, or a specific tissue type. Lately, however, there has been greater emphasis on finding the differential structure of the existing network topology under a novel condition or disease status to elucidate the perturbation in a biological system. In this review/tutorial article we briefly mention some of the research done in this area; we mainly illustrate the computational/statistical methods developed by our team in recent years for differential network analysis using publicly available gene expression data collected from a well known cancer study. This data includes a group of patients with acute lymphoblastic leukemia and a group with acute myeloid leukemia. In particular, we describe the statistical tests to detect the change in the network topology based on connectivity scores which measure the association or interaction between pairs of genes. The tests under various scores are applied to this data set to perform a differential network analysis on gene expression for human leukemia. We believe that, in the future, differential network analysis will be a standard way to view the changes in gene expression and protein expression data globally and these types of tests could be useful in analyzing the complex differential signatures.

  12. Scanning differential polarization microscope: Its use to image linear and circular differential scattering

    SciTech Connect

    Mickols, W.; Maestre, M.F.

    1988-06-01

    A differential polarization microscope that couples the sensitivity of single-beam measurement of circular dichroism and circular differential scattering with the simultaneous measurement of linear dichroism and linear differential scattering has been developed. The microscope uses a scanning microscope stage and single-point illumination to give the very shallow depth of field found in confocal microscopy. This microscope can operate in the confocal mode as well as in the near confocal condition that can allow one to program the coherence and spatial resolution of the microscope. This microscope has been used to study the change in the structure of chromatin during the development of sperm in Drosophila.

  13. Pathwise Strategies for Stochastic Differential Games with an Erratum to 'Stochastic Differential Games with Asymmetric Information'

    SciTech Connect

    Cardaliaguet, P.; Rainer, C.

    2013-08-01

    We introduce a new notion of pathwise strategies for stochastic differential games. This allows us to give a correct meaning to some statement asserted in Cardaliaguet and Rainer (Appl. Math. Optim. 59: 1-36, 2009)

  14. Effect of differential spectral reflectance on DIAL measurements using topographic targets. [Differential Absorption Lidar

    NASA Technical Reports Server (NTRS)

    Grant, W. B.

    1982-01-01

    Differential absorption lidar (DIAL) measurements of atmospheric gases and temperature made using topographic targets to provide the backscattered signal are subject to errors from the differential spectral reflectance of the target materials. The magnitude of this effect is estimated for a number of DIAL measurements reported in the literature. Calculations are presented for several topographic targets. In general the effect on a DIAL measurement increases directly with increasing wavelength and laser line separation, and inversely with differential absorption coefficient and distance to the target. The effect can be minimized by using tunable or isotope lasers to reduce the laser line separation or by using additional reference wavelengths to determine the surface differential spectral reflectance.

  15. Mechanical strain applied to human fibroblasts differentially regulates skeletal myoblast differentiation

    PubMed Central

    Hicks, Michael R.; Cao, Thanh V.; Campbell, David H.

    2012-01-01

    Cyclic short-duration stretches (CSDS) such as those resulting from repetitive motion strain increase the risk of musculoskeletal injury. Myofascial release is a common technique used by clinicians that applies an acyclic long-duration stretch (ALDS) to muscle fascia to repair injury. When subjected to mechanical strain, fibroblasts within muscle fascia secrete IL-6, which has been shown to induce myoblast differentiation, essential for muscle repair. We hypothesize that fibroblasts subjected to ALDS following CSDS induce myoblast differentiation through IL-6. Fibroblast conditioned media and fibroblast-myoblast cocultures were used to test fibroblasts' ability to induce myoblast differentiation. The coculture system applies strain to fibroblasts only but still allows for diffusion of potential differentiation mediators to unstrained myoblasts on coverslips. To determine the role of IL-6, we utilized myoblast unicultures ± IL-6 (0–100 ng/ml) and cocultures ± α-IL-6 (0–200 μg/ml). Untreated uniculture myoblasts served as a negative control. After 96 h, coverslips (n = 6–21) were microscopically analyzed and quantified by blinded observer for differentiation endpoints: myotubes per square millimeter (>3 nuclei/cell), nuclei/myotube, and fusion efficiency (%nuclei within myotubes). The presence of fibroblasts and fibroblast conditioned media significantly enhanced myotube number (P < 0.05). However, in coculture, CSDS applied to fibroblasts did not reproduce this effect. ALDS following CSDS increased myotube number by 78% and fusion efficiency by 96% vs. CSDS alone (P < 0.05). Fibroblasts in coculture increase IL-6 secretion; however, IL-6 secretion did not correlate with enhanced differentiation among strain groups. Exogenous IL-6 in myoblast uniculture failed to induce differentiation. However, α-IL-6 attenuated differentiation in all coculture groups (P < 0.05). Fibroblasts secrete soluble mediators that have profound effects on several measures of

  16. Mechanical strain applied to human fibroblasts differentially regulates skeletal myoblast differentiation.

    PubMed

    Hicks, Michael R; Cao, Thanh V; Campbell, David H; Standley, Paul R

    2012-08-01

    Cyclic short-duration stretches (CSDS) such as those resulting from repetitive motion strain increase the risk of musculoskeletal injury. Myofascial release is a common technique used by clinicians that applies an acyclic long-duration stretch (ALDS) to muscle fascia to repair injury. When subjected to mechanical strain, fibroblasts within muscle fascia secrete IL-6, which has been shown to induce myoblast differentiation, essential for muscle repair. We hypothesize that fibroblasts subjected to ALDS following CSDS induce myoblast differentiation through IL-6. Fibroblast conditioned media and fibroblast-myoblast cocultures were used to test fibroblasts' ability to induce myoblast differentiation. The coculture system applies strain to fibroblasts only but still allows for diffusion of potential differentiation mediators to unstrained myoblasts on coverslips. To determine the role of IL-6, we utilized myoblast unicultures ± IL-6 (0-100 ng/ml) and cocultures ± α-IL-6 (0-200 μg/ml). Untreated uniculture myoblasts served as a negative control. After 96 h, coverslips (n = 6-21) were microscopically analyzed and quantified by blinded observer for differentiation endpoints: myotubes per square millimeter (>3 nuclei/cell), nuclei/myotube, and fusion efficiency (%nuclei within myotubes). The presence of fibroblasts and fibroblast conditioned media significantly enhanced myotube number (P < 0.05). However, in coculture, CSDS applied to fibroblasts did not reproduce this effect. ALDS following CSDS increased myotube number by 78% and fusion efficiency by 96% vs. CSDS alone (P < 0.05). Fibroblasts in coculture increase IL-6 secretion; however, IL-6 secretion did not correlate with enhanced differentiation among strain groups. Exogenous IL-6 in myoblast uniculture failed to induce differentiation. However, α-IL-6 attenuated differentiation in all coculture groups (P < 0.05). Fibroblasts secrete soluble mediators that have profound effects on several measures of myoblast

  17. Fuzzy fractional functional differential equations under Caputo gH-differentiability

    NASA Astrophysics Data System (ADS)

    Hoa, Ngo Van

    2015-05-01

    In this paper the fuzzy fractional functional differential equations (FFFDEs) under the Caputo generalized Hukuhara differentiability are introduced. We study the existence and uniqueness results of solutions for FFFDEs under some suitable conditions. Also the solution to fuzzy fractional functional initial value problem under Caputo-type fuzzy fractional derivatives by a modified Adams-Bashforth-Moulton method (MABMM) is presented. The method is illustrated by solving some examples.

  18. Rail-to-rail differential input amplification stage with main and surrogate differential pairs

    DOEpatents

    Britton, Jr., Charles Lanier; Smith, Stephen Fulton

    2007-03-06

    An operational amplifier input stage provides a symmetrical rail-to-rail input common-mode voltage without turning off either pair of complementary differential input transistors. Secondary, or surrogate, transistor pairs assume the function of the complementary differential transistors. The circuit also maintains essentially constant transconductance, constant slew rate, and constant signal-path supply current as it provides rail-to-rail operation.

  19. New Improved Fractional Order Differentiator Models Based on Optimized Digital Differentiators

    PubMed Central

    Gupta, Maneesha

    2014-01-01

    Different evolutionary algorithms (EAs), namely, particle swarm optimization (PSO), genetic algorithm (GA), and PSO-GA hybrid optimization, have been used to optimize digital differential operators so that these can be better fitted to exemplify their new improved fractional order differentiator counterparts. First, the paper aims to provide efficient 2nd and 3rd order operators in connection with process of minimization of error fitness function by registering mean, median, and standard deviation values in different random iterations to ascertain the best results among them, using all the abovementioned EAs. Later, these optimized operators are discretized for half differentiator models for utilizing their restored qualities inhibited from their optimization. Simulation results present the comparisons of the proposed half differentiators with the existing and amongst different models based on 2nd and 3rd order optimized operators. Proposed half differentiators have been observed to approximate the ideal half differentiator and also outperform the existing ones reasonably well in complete range of Nyquist frequency. PMID:24688426

  20. Urine Proteins Identified by Two-Dimensional Differential Gel Electrophoresis Facilitate the Differential Diagnoses of Scrapie

    PubMed Central

    Lamoureux, Lise; Simon, Sharon L. R.; Plews, Margot; Ruddat, Viola; Brunet, Simone; Graham, Catherine; Czub, Stefanie; Knox, J. David

    2013-01-01

    The difficulty in developing a diagnostic assay for Creutzfeldt - Jakob disease (CJD) and other transmissible spongiform encephalopathies (TSEs) stems in part from the fact that the infectious agent is an aberrantly folded form of an endogenous cellular protein. This precludes the use of the powerful gene based technologies currently applied to the direct detection of other infectious agents. To circumvent this problem our research objective has been to identify a set of proteins exhibiting characteristic differential abundance in response to TSE infection. The objective of the present study was to assess the disease specificity of differentially abundant urine proteins able to identify scrapie infected mice. Two-dimensional differential gel electrophoresis was used to analyze longitudinal collections of urine samples from both prion-infected mice and a transgenic mouse model of Alzheimer's disease. The introduction of fluorescent dyes, that allow multiple samples to be co-resolved and visualized on one two dimensional gel, have increased the accuracy of this methodology for the discovery of robust protein biomarkers for disease. The accuracy of a small panel of differentially abundant proteins to correctly classify an independent naïve sample set was determined. The results demonstrated that at the time of clinical presentation the differential abundance of urine proteins were capable of identifying the prion infected mice with 87% sensitivity and 93% specificity. The identity of the diagnostic differentially abundant proteins was investigated by mass spectrometry. PMID:23704971

  1. Ethyl-2, 5-dihydroxybenzoate displays dual activity by promoting osteoblast differentiation and inhibiting osteoclast differentiation.

    PubMed

    Kwon, Byeong-Ju; Lee, Mi Hee; Koo, Min-Ah; Kim, Min Sung; Seon, Gyeung Mi; Han, Jae-Jin; Park, Jong-Chul

    2016-03-11

    The interplay between bone-forming osteoblasts and bone-resorbing osteoclasts is essential for balanced bone remodeling. In this study, we evaluate the ability of ethyl-2, 5-dihyrdoxybenzoate (E-2, 5-DHB) to affect both osteoblast and osteoclast differentiation for bone regeneration. Osteogenic differentiation of human mesenchymal stem cells (hMSCs) was quantified by measuring alkaline phosphatase (ALP) activity and calcium deposition. To evaluate osteoclast differentiation, we investigated the effect of E-2, 5-DHB on RANKL-activated osteoclastogenesis in RAW 264.7 cells. E-2, 5-DHB enhanced ALP activity and inhibited RAW 264.7 cell osteoclastogenesis in vitro. To assess the in vivo activity of E-2, 5-DHB, hMSCs were delivered subcutaneosuly alone or in combination with E-2, 5-DHB in an alginate gel into the backs of nude-mice. Histological and immunohistochemical evaluation showed significantly higher calcium deposition in the E-2, 5-DHB group. Osteocalcin (OCN) was highly expressed in cells implanted in the gels containing E-2, 5-DHB. Our results suggest that E-2, 5-DHB can effectively enhance osteoblast differentiation and inhibit osteoclast differentiation both in vitro and in vivo. Understanding the dual function of E-2, 5-DHB on osteoblast and osteoclast differentiation will aid in future development of E-2, 5-DHB as a material for bone tissue engineering.

  2. Differential requirement for OBF-1 during antibody-secreting cell differentiation

    PubMed Central

    Corcoran, Lynn M.; Hasbold, Jhagvaral; Dietrich, Wendy; Hawkins, Edwin; Kallies, Axel; Nutt, Stephen L.; Tarlinton, David M.; Matthias, Patrick; Hodgkin, Philip D.

    2005-01-01

    Resting B cells can be cultured to induce antibody-secreting cell (ASC) differentiation in vitro. A quantitative analysis of cell behavior during such a culture allows the influences of different stimuli and gene products to be measured. The application of this analytical system revealed that the OBF-1 transcriptional coactivator, whose loss impairs antibody production in vivo, has two effects on ASC development. Although OBF-1 represses early T cell–dependent (TD) differentiation, it is also critical for the completion of the final stages of ASC development. Under these conditions, the loss of OBF-1 blocks the genetic program of ASC differentiation so that Blimp-1/prdm1 induction fails, and bcl-6, Pax5, and AID are not repressed as in control ASC. Retroviral complementation confirmed that OBF-1 was the critical entity. Surprisingly, when cells were cultured in lipopolysaccharide to mimic T cell–independent conditions, OBF-1–null B cells differentiated normally to ASC. In the OBF-1−/− ASC generated under either culture regimen, antibody production was normal or only modestly reduced, revealing that Ig genes are not directly dependent on OBF-1 for their expression. The differential requirement for OBF-1 in TD ASC generation was confirmed in vivo. These studies define a new regulatory role for OBF-1 in determining the cell-autonomous capacity of B cells to undergo terminal differentiation in response to different immunological signals. PMID:15867091

  3. Regulation of chondrogenesis by protein kinase C: Emerging new roles in calcium signalling.

    PubMed

    Matta, Csaba; Mobasheri, Ali

    2014-05-01

    During chondrogenesis, complex intracellular signalling pathways regulate an intricate series of events including condensation of chondroprogenitor cells and nodule formation followed by chondrogenic differentiation. Reversible phosphorylation of key target proteins is of particular importance during this process. Among protein kinases known to be involved in these pathways, protein kinase C (PKC) subtypes play pivotal roles. However, the precise function of PKC isoenzymes during chondrogenesis and in mature articular chondrocytes is still largely unclear. In this review, we provide a historical overview of how the concept of PKC-mediated chondrogenesis has evolved, starting from the first discoveries of PKC isoform expression and activity. Signalling components upstream and downstream of PKC, leading to the stimulation of chondrogenic differentiation, are also discussed. Although it is evident that we are only at the beginning to understand what roles are assigned to PKC subtypes during chondrogenesis and how they are regulated, there are many yet unexplored aspects in this area. There is evidence that calcium signalling is a central regulator in differentiating chondroprogenitors; still, clear links between intracellular calcium signalling and prototypical calcium-dependent PKC subtypes such as PKCalpha have not been established. Exploiting putative connections and shedding more light on how exactly PKC signalling pathways influence cartilage formation should open new perspectives for a better understanding of healthy as well as pathological differentiation processes of chondrocytes, and may also lead to the development of novel therapeutic approaches. PMID:24440668

  4. Mechanical processess affecting differentiation of protolunar material

    NASA Technical Reports Server (NTRS)

    Kaula, W. M.

    1977-01-01

    Mechanisms prior to lunar formation are sought to account for the loss of volatiles, the depletion of iron, and the enrichment of plagioclase. Some of the same mechanisms are necessary to account for achondritic, stony-iron, and iron meteorites. Collisions seem marginally capable of providing the heat to accomplish the differentiation into iron, magnesian silicates, and plagioclase. Once this differentiation is accomplished, the subsequent mechanical history should have been sufficient to sort material according to composition in the protolunar circumterrestrial cloud. Effects operating include the correlation of body size with mechanical strength; the lesser ability of the cloud to trap the larger, denser infalling bodies; the more rapid drawing into the Earth of the larger moonlets; and the higher energy orbits for dominantly plagioclase smaller pieces broken off by collision.

  5. Biophysical mechanism of differential growth during gravitropism

    NASA Technical Reports Server (NTRS)

    Cosgrove, D.

    1984-01-01

    A research project is described the goal of which is to determine the mechanism of gravitropic curvature in plant stems at the biophysical and the cellular level. The reorientation of plant organs under the influence of gravity is due to differential growth of the upper and lower sides of the organ. The rate of plant cell enlargement is governed by four biophysical parameters: (1) the extensibility of the cell wall; (2) the minimum stress in the cell wall required for wall expansion (the "yield threshold'); (3) the osmotic pressure difference between the cell contents and the water source; and (4) the hydraulic conductivity of the pathway for water uptake. Gravitropic response must involve differential alteration of one or more of these four parameters on the two sides of the growing organ. Each of these factors will be examined to assess the role it plays in gravitropism.

  6. Earth fissures and localized differential subsidence.

    USGS Publications Warehouse

    Holzer, Thomas L.; Pampeyan, Earl H.

    1981-01-01

    Long linear tension cracks associated with declining groundwater levels at four sites in subsiding areas in south-central Arizona, Fremont Valley, California, and Las Vegas Valley, Nevada, occur near points of maximum convex-upward curvature in subsidence profiles oriented perpendicular to the cracks. Profiles are based on repeated precise vertical control surveys of lines of closely spaced bench marks. Association of these fissures with zones of localized differential subsidence indicates that linear earth fissures are caused by horizontal tensile strains probably resulting from localized differential compaction. Horizontal tensile strains across the fissures at the point of maximum convex-upward curvature, ranging from approximately 100 to 700 microstrains (0.01 to 0.07% per year), were indicated based on measurements with a tape or electronic distance meter.

  7. Electric wind in a Differential Mobility Analyzer

    DOE PAGES

    Palo, Marus; Meelis Eller; Uin, Janek; Tamm, Eduard

    2015-10-25

    Electric wind -- the movement of gas, induced by ions moving in an electric field -- can be a distorting factor in size distribution measurements using Differential Mobility Analyzers (DMAs). The aim of this study was to determine the conditions under which electric wind occurs in the locally-built VLDMA (Very Long Differential Mobility Analyzer) and TSI Long-DMA (3081) and to describe the associated distortion of the measured spectra. Electric wind proved to be promoted by the increase of electric field strength, aerosol layer thickness, particle number concentration and particle size. The measured size spectra revealed three types of distortion: wideningmore » of the size distribution, shift of the mode of the distribution to smaller diameters and smoothing out the peaks of the multiply charged particles. Electric wind may therefore be a source of severe distortion of the spectrum when measuring large particles at high concentrations.« less

  8. Investigating Population History Using Temporal Genetic Differentiation

    PubMed Central

    Skoglund, Pontus; Sjödin, Per; Skoglund, Tobias; Lascoux, Martin; Jakobsson, Mattias

    2014-01-01

    The rapid advance of sequencing technology, coupled with improvements in molecular methods for obtaining genetic data from ancient sources, holds the promise of producing a wealth of genomic data from time-separated individuals. However, the population-genetic properties of time-structured samples have not been extensively explored. Here, we consider the implications of temporal sampling for analyses of genetic differentiation and use a temporal coalescent framework to show that complex historical events such as size reductions, population replacements, and transient genetic barriers between populations leave a footprint of genetic differentiation that can be traced through history using temporal samples. Our results emphasize explicit consideration of the temporal structure when making inferences and indicate that genomic data from ancient individuals will greatly increase our ability to reconstruct population history. PMID:24939468

  9. Hybrid Differential Dynamic Programming with Stochastic Search

    NASA Technical Reports Server (NTRS)

    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.

  10. Bioprinting and Differentiation of Stem Cells.

    PubMed

    Irvine, Scott A; Venkatraman, Subbu S

    2016-01-01

    The 3D bioprinting of stem cells directly into scaffolds offers great potential for the development of regenerative therapies; in particular for the fabrication of organ and tissue substitutes. For this to be achieved; the lineage fate of bioprinted stem cell must be controllable. Bioprinting can be neutral; allowing culture conditions to trigger differentiation or alternatively; the technique can be designed to be stimulatory. Such factors as the particular bioprinting technique; bioink polymers; polymer cross-linking mechanism; bioink additives; and mechanical properties are considered. In addition; it is discussed that the stimulation of stem cell differentiation by bioprinting may lead to the remodeling and modification of the scaffold over time matching the concept of 4D bioprinting. The ability to tune bioprinting properties as an approach to fabricate stem cell bearing scaffolds and to also harness the benefits of the cells multipotency is of considerable relevance to the field of biomaterials and bioengineering. PMID:27617991

  11. Age and disability: explaining the wage differential.

    PubMed

    Gannon, Brenda; Munley, Margaret

    2009-07-01

    This paper estimates the level of explained and unexplained factors that contribute to the wage gap between workers with and without disabilities, providing benchmark estimates for Ireland. It separates out the confounding impact of productivity differences between disabled and non-disabled, by comparing wage differentials across three groups, disabled with limitations, disabled without limitations and non-disabled. Furthermore, data are analysed for the years 1995-2001 and two sub-samples pre and post 1998 allow us to decompose wage differentials before and after the Employment Equality Act 1998. Results are comparable to those of the UK and the unexplained component (upper bound of discrimination) is lower once we control for productivity differences. The lower bound level depends on the contribution of unobserved effects and the validity of the selection component in the decomposition model.

  12. Turbomachinery Airfoil Design Optimization Using Differential Evolution

    NASA Technical Reports Server (NTRS)

    Madavan, Nateri K.; Biegel, Bryan (Technical Monitor)

    2002-01-01

    An aerodynamic design optimization procedure that is based on a evolutionary algorithm known at Differential Evolution is described. Differential Evolution is a simple, fast, and robust evolutionary strategy that has been proven effective in determining the global optimum for several difficult optimization problems, including highly nonlinear systems with discontinuities and multiple local optima. The method is combined with a Navier-Stokes solver that evaluates the various intermediate designs and provides inputs to the optimization procedure. An efficient constraint handling mechanism is also incorporated. Results are presented for the inverse design of a turbine airfoil from a modern jet engine and compared to earlier methods. The capability of the method to search large design spaces and obtain the optimal airfoils in an automatic fashion is demonstrated. Substantial reductions in the overall computing time requirements are achieved by using the algorithm in conjunction with neural networks.

  13. Turbomachinery Airfoil Design Optimization Using Differential Evolution

    NASA Technical Reports Server (NTRS)

    Madavan, Nateri K.; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    An aerodynamic design optimization procedure that is based on a evolutionary algorithm known at Differential Evolution is described. Differential Evolution is a simple, fast, and robust evolutionary strategy that has been proven effective in determining the global optimum for several difficult optimization problems, including highly nonlinear systems with discontinuities and multiple local optima. The method is combined with a Navier-Stokes solver that evaluates the various intermediate designs and provides inputs to the optimization procedure. An efficient constraint handling mechanism is also incorporated. Results are presented for the inverse design of a turbine airfoil from a modern jet engine. The capability of the method to search large design spaces and obtain the optimal airfoils in an automatic fashion is demonstrated. Substantial reductions in the overall computing time requirements are achieved by using the algorithm in conjunction with neural networks.

  14. Sexual differentiation of the brain and behavior.

    PubMed

    Swaab, Dick F

    2007-09-01

    During the intrauterine period the human brain develops in the male direction via direct action of a boy's testosterone, and in the female direction through the absence of this hormone in a girl. During this time, gender identity (the feeling of being a man or a woman), sexual orientation, and other behaviors are programmed. As sexual differentiation of the genitals takes places in the first 2 months of pregnancy, and sexual differentiation of the brain starts during the second half of pregnancy, these two processes may be influenced independently of each other, resulting in transsexuality. This also means that in the case of an ambiguous gender at birth, the degree of masculinization of the genitals may not reflect the same degree of masculinization of the brain. Differences in brain structures and brain functions have been found that are related to sexual orientation and gender.

  15. Electric wind in a Differential Mobility Analyzer

    SciTech Connect

    Palo, Marus; Meelis Eller; Uin, Janek; Tamm, Eduard

    2015-10-25

    Electric wind -- the movement of gas, induced by ions moving in an electric field -- can be a distorting factor in size distribution measurements using Differential Mobility Analyzers (DMAs). The aim of this study was to determine the conditions under which electric wind occurs in the locally-built VLDMA (Very Long Differential Mobility Analyzer) and TSI Long-DMA (3081) and to describe the associated distortion of the measured spectra. Electric wind proved to be promoted by the increase of electric field strength, aerosol layer thickness, particle number concentration and particle size. The measured size spectra revealed three types of distortion: widening of the size distribution, shift of the mode of the distribution to smaller diameters and smoothing out the peaks of the multiply charged particles. Electric wind may therefore be a source of severe distortion of the spectrum when measuring large particles at high concentrations.

  16. Hybrid Differential Dynamic Programming with Stochastic Search

    NASA Technical Reports Server (NTRS)

    Aziz, Jonathan; Parker, Jeffrey; Englander, Jacob A.

    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 NASA's Dawn mission. The Dawn trajectory was designed with the DDP-based Static/Dynamic Optimal Control algorithm used in the Mystic software.1 Another recently developed method, Hybrid Differential Dynamic Programming (HDDP),2, 3 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.

  17. Differential rotation in solar convective dynamo simulations

    NASA Astrophysics Data System (ADS)

    Fan, Yuhong; Fang, Fang

    2016-10-01

    We carry out a magneto-hydrodynamic (MHD) simulation of convective dynamo in the rotating solar convective envelope driven by the solar radiative diffusive heat flux. The simulation is similar to that reported in Fan and Fang (2014) but with further reduced viscosity and magnetic diffusion. The resulting convective dynamo produces a large scale mean field that exhibits similar irregular cyclic behavior and polarity reversals, and self-consistently maintains a solar-like differential rotation. The main driver for the solar-like differential rotation (with faster rotating equator) is a net outward transport of angular momentum away from the rotation axis by the Reynolds stress, and we found that this transport is enhanced with reduced viscosity and magnetic diffusion.

  18. Monotone viable trajectories for functional differential inclusions

    NASA Astrophysics Data System (ADS)

    Haddad, Georges

    This paper is a study on functional differential inclusions with memory which represent the multivalued version of retarded functional differential equations. The main result gives a necessary and sufficient equations. The main result gives a necessary and sufficient condition ensuring the existence of viable trajectories; that means trajectories remaining in a given nonempty closed convex set defined by given constraints the system must satisfy to be viable. Some motivations for this paper can be found in control theory where F( t, φ) = { f( t, φ, u)} uɛU is the set of possible velocities of the system at time t, depending on the past history represented by the function φ and on a control u ranging over a set U of controls. Other motivations can be found in planning procedures in microeconomics and in biological evolutions where problems with memory do effectively appear in a multivalued version. All these models require viability constraints represented by a closed convex set.

  19. Use of labeled primers for differential display

    SciTech Connect

    Paunesku, T.; Woloschak, G.E.

    1995-01-01

    Two artifacts introduced in using differential display technology are (1) random priming from dT present from affinity purification of PolyA+ RNA and (2) hybridization of the arbitrary primer to template target sequences on both cDNA strands. We have developed a method eliminating both problems. By separately using 5`-end-labeled (T){sub 12}XY and arbitrary primers to label bands and comparing two differential display patterns, we can detect only those products incorporating the (T){sub 12}XY primer on the 3` ends and the arbitrary primer on 5` ends. Those bands that are generated randomly in the PCR are readily detectable and can be ignored.

  20. Visual determination of differential renal function

    SciTech Connect

    Kipper, M.S.; Witztum, K.F.; Taylor, A. Jr.

    1986-05-01

    Forty patients (43 studies) referred for determination of differential renal function were imaged 24 hours after intravenous administration of Tc-99m-2, 3 DMSA. Visual assessment of relative renal uptake was estimated independently by three observers at three different hospitals from analog images on standard x-ray film. The results were compared with the relative DMSA uptake obtained by summing counts in computer-assisted regions of interest placed over each kidney. There was excellent correlation between the visual estimates of each observer and the computer-generated values (r = 0.98, 0.96, and 0.98, respectively). If a computer is not available, good visual estimates of differential uptake still may be obtained when static imaging agents such as DMSA are administered.

  1. Positive solutions of advanced differential systems.

    PubMed

    Diblík, Josef; Kúdelčíková, Mária

    2013-01-01

    We study asymptotic behavior of solutions of general advanced differential systems y(t) = F(t, y(t)), where F : Ω → [Symbol: see text] (n) is a continuous quasi-bounded functional which satisfies a local Lipschitz condition with respect to the second argument and Ω is a subset in [Symbol: see text] × C(r)(n), C(r)(n) := C([0, r], [Symbol: see text] (n)), y t [Symbol: see text]C(r)(n), and y t (θ) = y(t + θ), θ [Symbol: see text] [0, r]. A monotone iterative method is proposed to prove the existence of a solution defined for t → ∞ with the graph coordinates lying between graph coordinates of two (lower and upper) auxiliary vector functions. This result is applied to scalar advanced linear differential equations. Criteria of existence of positive solutions are given and their asymptotic behavior is discussed.

  2. Differential Resonant Ring YIG Tuned Oscillator

    NASA Technical Reports Server (NTRS)

    Parrott, Ronald A.

    2010-01-01

    A differential SiGe oscillator circuit uses a resonant ring-oscillator topology in order to electronically tune the oscillator over multi-octave bandwidths. The oscillator s tuning is extremely linear, because the oscillator s frequency depends on the magnetic tuning of a YIG sphere, whose resonant frequency is equal to a fundamental constant times the DC magnetic field. This extremely simple circuit topology uses two coupling loops connecting a differential pair of SiGe bipolar transistors into a feedback configuration using a YIG tuned filter creating a closed-loop ring oscillator. SiGe device technology is used for this oscillator in order to keep the transistor s 1/f noise to an absolute minimum in order to achieve minimum RF phase noise. The single-end resonant ring oscillator currently has an advantage in fewer parts, but when the oscillation frequency is greater than 16 GHz, the package s parasitic behavior couples energy to the sphere and causes holes and poor phase noise performance. This is because the coupling to the YIG is extremely low, so that the oscillator operates at near the unloaded Q. With the differential resonant ring oscillator, the oscillation currents are just in the YIG coupling mechanisms. The phase noise is even better, and the physical size can be reduced to permit monolithic microwave integrated circuit oscillators. This invention is a YIG tuned oscillator circuit making use of a differential topology to simultaneously achieve an extremely broadband electronic tuning range and ultra-low phase noise. As a natural result of its differential circuit topology, all reactive elements, such as tuning stubs, which limit tuning bandwidth by contributing excessive open loop phase shift, have been eliminated. The differential oscillator s open-loop phase shift is associated with completely non-dispersive circuit elements such as the physical angle of the coupling loops, a differential loop crossover, and the high-frequency phase shift of the n

  3. Ultrasonographic Differentiation of Lateral Elbow Pain.

    PubMed

    Obuchowicz, R; Bonczar, M

    2016-05-01

    Lateral elbow pain is often attributed to degenerative or posttraumatic impairment of the common extensor tendon. Ultrasonography assesses the soft tissue structures of the lateral elbow, allowing the differentiation between various underlying processes, including angiofibroblastic degeneration, hyaline degeneration, and inflammation, and exclusion of other possible causes of pain such as posterior interosseous and lateral antebrachial nerve compression. Furthermore, the real-time imaging nature of ultrasonography enables the detection of impingement of the lateral synovial fold, degenerative changes in the elbow recess, and elbow posterolateral instability during dynamic maneuvers. Ultrasonography is widely accessible and well tolerated by patients, making it a perfect method for establishing an initial diagnosis and monitoring the healing process. This review describes the possible causes of lateral elbow pain and their ultrasonographic differentiation. PMID:27689169

  4. Weak self-adjoint differential equations

    NASA Astrophysics Data System (ADS)

    Gandarias, M. L.

    2011-07-01

    The concepts of self-adjoint and quasi self-adjoint equations were introduced by Ibragimov (2006 J. Math. Anal. Appl. 318 742-57 2007 Arch. ALGA 4 55-60). In Ibragimov (2007 J. Math. Anal. Appl. 333 311-28), a general theorem on conservation laws was proved. In this paper, we generalize the concept of self-adjoint and quasi self-adjoint equations by introducing the definition of weak self-adjoint equations. We find a class of weak self-adjoint quasi-linear parabolic equations. The property of a differential equation to be weak self-adjoint is important for constructing conservation laws associated with symmetries of the differential equation.

  5. Differentiation signatures in the Flora region

    NASA Astrophysics Data System (ADS)

    Oszkiewicz, Dagmara; Kankiewicz, Paweł; Włodarczyk, Ireneusz; Kryszczyńska, Agnieszka

    2015-12-01

    Context. Most asteroid families are very homogeneous in physical properties. Some show greater diversity, however. The Flora family is the most intriguing of them. The Flora family is spread widely in the inner main belt, has a rich collisional history, and is one of the most taxonomically diverse regions in the main belt. As a result of its proximity to the asteroid (4) Vesta (the only currently known intact differentiated asteroid) and its family, migration between the two regions is possible. This dynamical path is one of the counter arguments to the hypothesis that there may be traces of a differentiated parent body other than Vesta in the inner main belt region. We here investigate the possibility that some of the V- and A-types (commonly interpreted as basaltoids and dunites - parts of the mantle and crust of differentiated parent bodies) in the Flora dynamical region are not dynamically connected to Vesta. Aims: The goal of this study is to investigate asteroids in the Flora dynamical region that may be witness to the differentiation of a parent body other than (4) Vesta. In particular, we aim at predicting which asteroids may be fragments of a differentiated body or bodies (taxonomical V-types). We also investigate their possible dynamical linkage to the nearby Vesta family. Methods: To predict the taxonomic types of asteroids we used the naive Bayes classifier. We studied their dynamical past through numerical integration including gravitational and Yarkovsky forces. Each asteroid was cloned, and average orbital elements were computed at each step. When possible, we used observationally constrained physical parameters for the thermal forces. Results: Most of the asteroids in the Flora region are predicted to originate from the S-complex (around 47.8%). Tens of asteroids with potentially differential origins are identified in the region, including 164 potential V-types. We investigated the dynamical evolution of selected objects to examine possible linkages

  6. Ultrasonographic Differentiation of Lateral Elbow Pain

    PubMed Central

    Obuchowicz, R.; Bonczar, M.

    2016-01-01

    Lateral elbow pain is often attributed to degenerative or posttraumatic impairment of the common extensor tendon. Ultrasonography assesses the soft tissue structures of the lateral elbow, allowing the differentiation between various underlying processes, including angiofibroblastic degeneration, hyaline degeneration, and inflammation, and exclusion of other possible causes of pain such as posterior interosseous and lateral antebrachial nerve compression. Furthermore, the real-time imaging nature of ultrasonography enables the detection of impingement of the lateral synovial fold, degenerative changes in the elbow recess, and elbow posterolateral instability during dynamic maneuvers. Ultrasonography is widely accessible and well tolerated by patients, making it a perfect method for establishing an initial diagnosis and monitoring the healing process. This review describes the possible causes of lateral elbow pain and their ultrasonographic differentiation. PMID:27689169

  7. New finite difference formulas for numerical differentiation

    NASA Astrophysics Data System (ADS)

    Khan, Ishtiaq Rasool; Ohba, Ryoji

    2000-12-01

    Conventional numerical differentiation formulas based on interpolating polynomials, operators and lozenge diagrams can be simplified to one of the finite difference approximations based on Taylor series, and closed-form expressions of these finite difference formulas have already been presented. In this paper, we present new finite difference formulas, which are more accurate than the available ones, especially for the oscillating functions having frequency components near the Nyquist frequency. Closed-form expressions of the new formulas are given for arbitrary order. A comparison of the previously available three types of approximations is given with the presented formulas. A computer program written in MATHEMATICA, based on new formulas is given in the appendix for numerical differentiation of a function at a specified mesh point.

  8. Differential method for processing scanning lidar data.

    PubMed

    Kovalev, Vladimir

    2015-11-20

    The significant deficiency of the classic multiangle data-processing technique is that the accuracy of the lidar-data inversion strongly depends on whether the assumption of the horizontal stratification of the searched atmosphere is valid. The aggravating factor is that no reliable methodology exists that would allow establishment of whether the above assumption is met; even the thorough analysis of the measured lidar signals rarely allows for a reliable conclusion about the fulfillment of this requirement. In this study, a new multiangle differential data-processing method is considered, which provides the renewed interpretation of multiangle measurements. It allows for distinguishing and separating the data points from the areas where the backscatter extinction coefficient is not constant in the horizontal directions. Simulated and experimental data are presented that illustrate the principle and specifics of such a differential technique. PMID:26836537

  9. High Bandwidth Differential Amplifier for Shock Experiments

    SciTech Connect

    Ross, P. W., Tran, V., Chau, R.

    2012-04-30

    We developed a high bandwidth differential amplifier for gas gun shock experiments/applications. The circuit has a bandwidth > 1 GHz, and is capable of measuring signals of ≤1.5 V with a common mode rejection of 250 V. Conductivity measurements of gas gun targets are measured by flowing high currents through the targets. The voltage is measured across the target using a technique similar to a four-point probe. Because of the design of the current source and load, the target voltage is approximately 250 V relative to ground. Since the expected voltage change in the target is < 1 V, the differential amplifier must have a large common mode rejection. High pass filters suppress internal ringing of operational amplifiers. Results of bench tests are shown.

  10. Ultrasonographic Differentiation of Lateral Elbow Pain

    PubMed Central

    Obuchowicz, R.; Bonczar, M.

    2016-01-01

    Lateral elbow pain is often attributed to degenerative or posttraumatic impairment of the common extensor tendon. Ultrasonography assesses the soft tissue structures of the lateral elbow, allowing the differentiation between various underlying processes, including angiofibroblastic degeneration, hyaline degeneration, and inflammation, and exclusion of other possible causes of pain such as posterior interosseous and lateral antebrachial nerve compression. Furthermore, the real-time imaging nature of ultrasonography enables the detection of impingement of the lateral synovial fold, degenerative changes in the elbow recess, and elbow posterolateral instability during dynamic maneuvers. Ultrasonography is widely accessible and well tolerated by patients, making it a perfect method for establishing an initial diagnosis and monitoring the healing process. This review describes the possible causes of lateral elbow pain and their ultrasonographic differentiation.

  11. Recursively indexed differential pulse code modulation

    NASA Technical Reports Server (NTRS)

    Sayood, Khalid; Na, Sangsin

    1992-01-01

    The performance of a differential pulse code modulation (DPCM) system with a recursively indexed quantizer (RIQ) under various conditions, with first order Gauss-Markov and Laplace-Markov sources as inputs, is studied. When the predictor is matched to the input, the proposed system performs at or close to the optimum entropy constrained DPCM system. If one is willing to accept a 5 percent increase in the rate, the system is very forgiving of predictor mismatch.

  12. Differential phase shift quantum key distribution.

    PubMed

    Inoue, Kyo; Waks, Edo; Yamamoto, Yoshihisa

    2002-07-15

    A novel quantum cryptography scheme is proposed, in which a single photon is prepared in a linear superposition state of three basis kets. A photon split to three pulses is sent from Alice to Bob, where the phase difference between sequential two pulses carries bit information. Bob measures the phase difference by passive differential phase detection. This scheme is suitable for fiber transmission systems and offers a key creation efficiency higher than conventional fiber-based BB84. PMID:12144419

  13. Differential Gene Action in Neurospora crassa

    PubMed Central

    Bhagwat, A. S.; Mahadevan, P. R.

    1973-01-01

    Molecular hybridization experiments with pulse-labeled total ribonucleic acid (RNA) or isolated nonribosomal rapidly labeled RNA species and deoxyribonucleic acid from growth periods of 8, 16, and 24 hr of Neurospora crassa showed differential transcription. Hybridization competition experiments between RNA species isolated from 8, 16, and 24 hr of growth showed qualitative differences in the types of RNA synthesized during these periods. PMID:4266171

  14. LORENE: Spectral methods differential equations solver

    NASA Astrophysics Data System (ADS)

    Gourgoulhon, Eric; Grandclément, Philippe; Marck, Jean-Alain; Novak, Jérôme; Taniguchi, Keisuke

    2016-08-01

    LORENE (Langage Objet pour la RElativité NumériquE) solves various problems arising in numerical relativity, and more generally in computational astrophysics. It is a set of C++ classes and provides tools to solve partial differential equations by means of multi-domain spectral methods. LORENE classes implement basic structures such as arrays and matrices, but also abstract mathematical objects, such as tensors, and astrophysical objects, such as stars and black holes.

  15. Tests Of A Differential Global Positioning System

    NASA Technical Reports Server (NTRS)

    Edwards, F. G.; Hegary, D. M.; Turner, R. N.; Van Graas, F.; Sharma, S.

    1990-01-01

    Paper describes validation tests of global positioning system (GPS) for low-flying helicopters. Configured as differential GPS, in which components in both aircraft and ground station compute position errors relative to known location using satellite navigational data. Corrections computed from differences between computed and measured ranges to four satellites being tracked by receiver in both aircraft and ground systems. Tests conducted to determine whether equipment and computer programs of system operated correctly and consistently.

  16. Antigen presenting cells - diversity, differentiation, and regulation

    SciTech Connect

    Schook, L.B. ); Tew, J.G. )

    1988-01-01

    This book contains 35 papers. Some of the titles are: DNA-mediated gene transfer as a tool for analyzing Ia structure-function relationships and antigen presentation; Regulation of immune-associated genes during macrophage differentiation; Presentation of arsonate-tyrosine to cloned T-cells by L-Cells transfected with class II genes; and The duration of class II MHC glycoprotein expression by mononuclear phagocytes is regulated by the Bcg gene.

  17. Introducing Knowledge into Differential Expression Analysis

    PubMed Central

    Biecek, Przemysław; Tiuryn, Jerzy; Vingron, Martin

    2010-01-01

    Abstract Gene expression measurements allow determining sets of up- or down-regulated, or unchanged genes in a particular experimental condition. Additional biological knowledge can suggest examples of genes from one of these sets. For instance, known target genes of a transcriptional activator are expected, but are not certain to go down after this activator is knocked out. Available differential expression analysis tools do not take such imprecise examples into account. Here we put forward a novel partially supervised mixture modeling methodology for differential expression analysis. Our approach, guided by imprecise examples, clusters expression data into differentially expressed and unchanged genes. The partially supervised methodology is implemented by two methods: a newly introduced belief-based mixture modeling, and soft-label mixture modeling, a method proved efficient in other applications. We investigate on synthetic data the input example settings favorable for each method. In our tests, both belief-based and soft-label methods prove their advantage over semi-supervised mixture modeling in correcting for erroneous examples. We also compare them to alternative differential expression analysis approaches, showing that incorporation of knowledge yields better performance. We present a broad range of knowledge sources and data to which our partially supervised methodology can be applied. First, we determine targets of Ste12 based on yeast knockout data, guided by a Ste12 DNA-binding experiment. Second, we distinguish miR-1 from miR-124 targets in human by clustering expression data under transfection experiments of both microRNAs, using their computationally predicted targets as examples. Finally, we utilize literature knowledge to improve clustering of time-course expression profiles. PMID:20726790

  18. Diaper Dermatitis: Differential Diagnosis and Management

    PubMed Central

    Kellen, Philippa E.

    1990-01-01

    Diaper dermatitis is one of the most common dermatoses occurring in infancy. It is an irritant dermatitis, in which a variety of factors act in concert to produce inflammation of the diapered skin. The differential diagnosis includes many common and some uncommon conditions. Successful treatment requires detailed instructions to caregivers regarding simple hygienic procedures and diapering practices. ImagesFigure 1Figure 2 PMID:21233927

  19. Stable Isotope Evidence for Planetary Differentiation

    NASA Astrophysics Data System (ADS)

    Shahar, A.; Mao, W. L.; Schauble, E. A.; Caracas, R.; Reagan, M. M.; Gleason, A. E.

    2015-12-01

    Planetary differentiation occurred at high temperature and varying oxygen fugacity, on bodies with varying compositions and internal pressures. The specific conditions at which bodies differentiated and the chemical fingerprints left by differentiation can be investigated by measuring stable isotope ratios in natural samples. Much can be learned by combining those data with experiments that systematically investigate the chemical and physical conditions within differentiating bodies. In this talk we focus on one variable in particular that has not been well defined with respect to stable isotope fractionation: pressure. We will present new iron isotope data on how pressure affects isotope fractionation factors for a number of iron compounds relative to silicate. The processes governing iron isotope fractionation in igneous rocks have been debated extensively over the past decade. Analyses of natural samples show that iron isotopes are fractionated at both the whole rock and mineral scales. This fractionation has been interpreted to be a result of several processes including a possible signature of high pressure core formation. We have collected new high pressure synchrotron nuclear resonant inelastic x-ray scattering data from Sector 16-ID-D at the Advanced Photon Source on 57Fe enriched Fe, FeO, FeHx and Fe3C. Our data show clear trends with pressure implying that not only does pressure have an effect on the iron isotope beta factors but also a fractionation amongst the alloys. This suggests that depending on the light element in the core, there will be a different resulting signature in the iron isotope record. We will discuss the likelihood of different light elements in the core based on these results, as well as the theoretical predictions for the same phases. Finally, we will present the fractionation expected between metal and silicate at high pressure and high temperature in order to determine if core formation would indeed leave an isotopic signature in

  20. GATA2 regulates dendritic cell differentiation

    PubMed Central

    Onodera, Koichi; Fujiwara, Tohru; Onishi, Yasushi; Itoh-Nakadai, Ari; Okitsu, Yoko; Fukuhara, Noriko; Ishizawa, Kenichi; Shimizu, Ritsuko; Yamamoto, Masayuki

    2016-01-01

    Dendritic cells (DCs) are critical immune response regulators; however, the mechanism of DC differentiation is not fully understood. Heterozygous germ line GATA2 mutations induce GATA2-deficiency syndrome, characterized by monocytopenia, a predisposition to myelodysplasia/acute myeloid leukemia, and a profoundly reduced DC population, which is associated with increased susceptibility to viral infections, impaired phagocytosis, and decreased cytokine production. To define the role of GATA2 in DC differentiation and function, we studied Gata2 conditional knockout and haploinsufficient mice. Gata2 conditional deficiency significantly reduced the DC count, whereas Gata2 haploinsufficiency did not affect this population. GATA2 was required for the in vitro generation of DCs from Lin−Sca-1+Kit+ cells, common myeloid-restricted progenitors, and common dendritic cell precursors, but not common lymphoid-restricted progenitors or granulocyte-macrophage progenitors, suggesting that GATA2 functions in the myeloid pathway of DC differentiation. Moreover, expression profiling demonstrated reduced expression of myeloid-related genes, including mafb, and increased expression of T-lymphocyte–related genes, including Gata3 and Tcf7, in Gata2-deficient DC progenitors. In addition, GATA2 was found to bind an enhancer element 190-kb downstream region of Gata3, and a reporter assay exhibited significantly reduced luciferase activity after adding this enhancer region to the Gata3 promoter, which was recovered by GATA sequence deletion within Gata3 +190. These results suggest that GATA2 plays an important role in cell-fate specification toward the myeloid vs T-lymphocyte lineage by regulating lineage-specific transcription factors in DC progenitors, thereby contributing to DC differentiation. PMID:27259979