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Sample records for atdc5 chondroprogenitors differentiating

  1. Effects of retinoic acid on the differentiation of chondrogenic progenitor cells, ATDC5.

    PubMed

    Kirimoto, Akiko; Takagi, Yuzo; Ohya, Keiichi; Shimokawa, Hitoyata

    2005-09-01

    Chondrocyte differentiation is a fundamental process during endochondral ossification. Retinoic acid (RA) has been shown to regulate this process, however, the mechanisms underlying RA regulation of chondrogenesis are not clearly understood. Chondroprogenitor cells, ATDC5 have been shown to be a useful in vitro model for examining the multiple step differentiation of chondrocytes. The present study investigated the mechanisms underlying RA regulation of chondrogenesis using ATDC5 cell culture. In this study, we show that RA suppresses the cell growth, cartilage nodule formation, accumulation of proteoglycan, alkaline phosphatase (ALPase) activity and mineralization and that RA dose dependently upregulates the levels of type X collagen and matrix metalloproteinase-13 (MMP-13) mRNA which are marker proteins of hypertrophic chondrocytes, in ATDC5 cells. The addition of protein synthesis inhibitor, cycloheximide (CHX), partially inhibits the induction of type X collagen and MMP-13 mRNA by RA. In this system, RA upregulates the mRNA level of Runx2/Cbfa1 (type II), a positive regulator for mineralization, and downregulates the mRNA of Indian hedgehog (Ihh), parathyroid hormone related protein (PTHrP), negative regulators for terminal differentiation. However, RA downregulates ALPase, bone gla protein (BGP) mRNAs and mineralization. These data indicate that RA stimulates cartilage differentiation, however, cell condensation and cartilage nodule formation may be candidates of primary importance in the terminal differentiation of chondrocytes. PMID:16350840

  2. 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

  3. Glucocorticoid effects on chondrogenesis, differentiation and apoptosis in the murine ATDC5 chondrocyte cell line.

    PubMed

    Mushtaq, T; Farquharson, C; Seawright, E; Ahmed, S F

    2002-12-01

    Glucocorticoids (GC) are used extensively in children and may cause growth retardation, which is in part due to the direct effects of GC on the growth plate. We characterised the ATDC5 chondrocyte cell line, which mimics the in vivo process of longitudinal bone growth, to examine the effects of dexamethasone (Dex) and prednisolone (Pred) during two key time points in the chondrocyte life cycle - chondrogenesis and terminal differentiation. Additionally, we studied the potential for recovery following Dex exposure. During chondrogenesis, Dex and Pred exposure at 10(-8) M, 10(-7) M and 10(-6) M resulted in a significant mean reduction in cell number (28% vs 20%), cell proliferation (27% vs 24%) and proteoglycan synthesis (47% vs 43%) and increased alkaline phosphatase (ALP) activity (106% vs 62%), whereas the incidence of apoptosis was unaltered. Minimal effects were noted during terminal differentiation with both GC although all concentrations of Dex lowered apoptotic cell number. To assess catch-up growth the cells were incubated for a total of 14 days which included 1, 3, 7, 10 or 14 days exposure to 10(-6) M Dex, prior to the recovery period. Recovery of proteoglycan synthesis was irreversibly impaired following just one day exposure to Dex. Although cell number showed a similar pattern, significant impairment was only achieved following 14 days exposure. Irreversible changes in ALP activity were only noticed following 10 days exposure to Dex. In conclusion, GC have maximal effects during chondrogenesis; Dex is more potent than Pred and cells exposed to Dex recover but this may be restricted due to differential effects of GC on specific chondrocyte phenotypes. PMID:12475381

  4. 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

  5. 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

  6. 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.

  7. 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. PMID:25196420

  8. Significant increase in Young's modulus of ATDC5 cells during chondrogenic differentiation induced by PAMPS/PDMAAm double-network gel: comparison with induction by insulin.

    PubMed

    Maeda, Eijiro; Tsutsumi, Takehiro; Kitamura, Nobuto; Kurokawa, Takayuki; Ping Gong, Jian; Yasuda, Kazunori; Ohashi, Toshiro

    2014-10-17

    A double-network (DN) gel, which was composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N'-dimethyl acrylamide) (PAMPS/PDMAAm), has the potential to induce chondrogenesis both in vitro and in vivo. The present study investigated the biomechanical and biological responses of chondrogenic progenitor ATDC5 cells cultured on the DN gel. ATDC5 cells were cultured on a polystyrene surface without insulin (Culture 1) and with insulin (Culture 2), and on the DN gel without insulin (Culture 3). The cultured cells were evaluated using micropipette aspiration for cell Young's modulus and qPCR for gene expression of chondrogenic and actin organization markers on days 3, 7 and 14. On day 3, the cells in Culture 3 formed nodules, in which the cells exhibited an actin cortical layer inside them, and gene expression of type-II collagen, aggrecan, and SOX9 was significantly higher in Culture 3 than Cultures 1 and 2 (p<0.05). Young's modulus in Culture 3 was significantly higher than that in Culture 1 throughout the testing period (p<0.05) and that in Culture 2 on day 14 (p<0.01). There was continuous expression of actin organization markers in Culture 3. This study highlights that the cells on the DN gel increased the modulus and mRNA expression of chondrogenic markers at an earlier time point with a greater magnitude compared to those on the polystyrene surface with insulin. This study also demonstrates a possible strong interrelation among alteration of cell mechanical properties, changes in actin organization and the induction of chondrogenic differentiation. PMID:25110167

  9. 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

  10. 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

  11. 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.

  12. Presence and function of microRNA-92a in chondrogenic ATDC5 and adipose-derived mesenchymal stem cells

    PubMed Central

    HOU, CHANGHE; ZHANG, ZIJI; ZHANG, ZHIQI; WU, PEIHUI; ZHAO, XIAOYI; FU, MING; SHENG, PUYI; KANG, YAN; LIAO, WEIMING

    2015-01-01

    The aim of the present study was to investigate the presence and biological function of microRNA-92a (miR-92a) in chondrogenesis and cartilage degeneration. Human adipose-derived mesenchymal stem cells (hADSCs) in micromass and chondrocyte-like ATDC5 cells were induced to chondrogenesis, and primary human/mouse chondrocytes (PHCs/PMCs) and chondrogenic ATDC5 cells were stimulated with interleukin-1β (IL-1β). An miR-92a mimic/inhibitor was transfected into the ATDC5 cells using lipofectamine 2000. Gene expression was analyzed using reverse transcription-quantitative polymerase chain reaction. Alcian blue was used to stain the cartilage nodules and chondrogenic micromass. The potential target genes, signaling pathways and functions of miR-92a were examined using miRanda, miRDB, CLIP-Seq, TargetScan and Kyoto Encyclopedia of Genes and Genomes. The expression of miR-92a was elevated in the chondrogenic ATDC5 cells and hADSCs, and also in the IL-1β-induced ATDC5 cells, PMCs and PHCs. Forced expression of miR-92a enhanced the expression levels of col9a2 and aggrecan. A total of 279 genes were predicted as potential target genes of miR-92a. The phosphoinositide 3-kinase/PI3K)-Akt, ErbB and focal adhesion kinase pathways, extracellular matrix (ECM)-receptor interaction and the mammalian target of rapamycin (mTOR) signaling pathway were suggested to mediate the effects of miR-92a on chondrogenesis and cartilage degeneration. These results demonstrated that miR-92a was involved in chondrogenesis and the chondrocyte response induced by IL-1β. miR-92a positively contributed to the expression of col9a2 and of aggrecan. PMID:26135269

  13. The enhancement of chondrogenesis of ATDC5 cells in RGD-immobilized microcavitary alginate hydrogels.

    PubMed

    Yao, Yongchang; Zeng, Lei; Huang, Yuyang

    2016-07-01

    In our previous work, we have developed an effective microcavitary alginate hydrogel for proliferation of chondrocytes and maintenance of chondrocytic phenotype. In present work, we investigated whether microcavitary alginate hydrogel could promote the chondrogenesis of progenitor cells. Moreover, we attempted to further optimize this system by incorporating synthetic Arg-Gly-Asp peptide. ATDC5 cells were seeded into microcavitary alginate hydrogel with or without Arg-Gly-Asp immobilization. Cell Counting Kit-8 and live/dead staining were conducted to analyze cell proliferation. Real-time polymerase chain reaction (RT-PCR), hematoxylin and eosin, and Toluidine blue O staining as well as Western blot assay was performed to evaluate the cartilaginous markers at transcriptional level and at protein level, respectively. The obtained data demonstrated that Arg-Gly-Asp-immobilized microcavitary alginate hydrogel was preferable to promote the cell proliferation. Also, Arg-Gly-Asp-immobilized microcavitary alginate hydrogel improved the expression of chondrocytic genes including Collagen II and Aggrecan when compared with microcavitary alginate hydrogel. The results suggested that microcavitary alginate hydrogel could promote the chondrogenesis. And Arg-Gly-Asp would be promising to ameliorate this culture system for cartilage tissue engineering. PMID:27000189

  14. P5L mutation in Ank results in an increase in extracellular inorganic pyrophosphate during proliferation and nonmineralizing hypertrophy in stably transduced ATDC5 cells

    PubMed Central

    Zaka, Raihana; Stokes, David; Dion, Arnold S; Kusnierz, Anna; Han, Fei; Williams, Charlene J

    2006-01-01

    Ank is a multipass transmembrane protein that regulates the cellular transport of inorganic pyrophosphate. In the progressive ankylosis (ank) mouse, a premature termination mutation at glutamic acid 440 results in a phenotype characterized by inappropriate deposition of basic calcium phosphate crystals in skeletal tissues. Mutations in the amino terminus of ANKH, the human homolog of Ank, result in familial calcium pyrophosphate dihydrate deposition disease. It has been hypothesized that these mutations result in a gain-of-function with respect to the elaboration of extracellular inorganic pyrophosphate. To explore this issue in a mineralization-competent system, we stably transduced ATDC5 cells with wild-type Ank as well as with familial chondrocalcinosis-causing Ank mutations. We evaluated the elaboration of inorganic pyrophosphate, the activity of pyrophosphate-modulating enzymes, and the mineralization in the transduced cells. Expression of transduced protein was confirmed by quantitative real-time PCR and by ELISA. Levels of inorganic pyrophosphate were measured, as were the activities of nucleotide pyrophosphatase phosphodiesterase and alkaline phosphatase. We also evaluated the expression of markers of chondrocyte maturation and the nature of the mineralization phase elaborated by transduced cells. The cell line expressing the proline to leucine mutation at position 5 (P5L) consistently displayed higher levels of extracellular inorganic pyrophosphate and higher phosphodiesterase activity than the other transduced lines. During hypertrophy, however, extracellular inorganic pyrophosphate levels were modulated by alkaline phosphatase activity in this cell system, resulting in the deposition of basic calcium phosphate crystals only in all transduced cell lines. Cells overexpressing wild-type Ank displayed a higher level of expression of type X collagen than cells transduced with mutant Ank. Other markers of hypertrophy and terminal differentiation, such as

  15. 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

  16. Stable 5-Hydroxymethylcytosine (5hmC) Acquisition Marks Gene Activation During Chondrogenic Differentiation.

    PubMed

    Taylor, Sarah Eb; Li, Ye Henry; Smeriglio, Piera; Rath, Madhusikta; Wong, Wing H; Bhutani, Nidhi

    2016-03-01

    Regulation of gene expression changes during chondrogenic differentiation by DNA methylation and demethylation is little understood. Methylated cytosines (5mC) are oxidized by the ten-eleven-translocation (TET) proteins to 5-hydroxymethylcytosines (5hmC), 5-formylcytosines (5fC), and 5-carboxylcytosines (5caC), eventually leading to a replacement by unmethylated cytosines (C), ie, DNA demethylation. Additionally, 5hmC is stable and acts as an epigenetic mark by itself. Here, we report that global changes in 5hmC mark chondrogenic differentiation in vivo and in vitro. Tibia anlagen and growth plate analyses during limb development at mouse embryonic days E 11.5, 13.5, and 17.5 showed dynamic changes in 5hmC levels in the differentiating chondrocytes. A similar increase in 5hmC levels was observed in the ATDC5 chondroprogenitor cell line accompanied by increased expression of the TET proteins during in vitro differentiation. Loss of TET1 in ATDC5 decreased 5hmC levels and impaired differentiation, demonstrating a functional role for TET1-mediated 5hmC dynamics in chondrogenic differentiation. Global analyses of the 5hmC-enriched sequences during early and late chondrogenic differentiation identified 5hmC distribution to be enriched in the regulatory regions of genes preceding the transcription start site (TSS), as well as in the gene bodies. Stable gains in 5hmC were observed in specific subsets of genes, including genes associated with cartilage development and in chondrogenic lineage-specific genes. 5hmC gains in regulatory promoter and enhancer regions as well as in gene bodies were strongly associated with activated but not repressed genes, indicating a potential regulatory role for DNA hydroxymethylation in chondrogenic gene expression. © 2015 American Society for Bone and Mineral Research. PMID:26363184

  17. Tenascin-W inhibits proliferation and differentiation of preosteoblasts during endochondral bone formation

    SciTech Connect

    Kimura, Hiroaki; Akiyama, Haruhiko . E-mail: hakiyama@kuhp.kyoto-u.ac.jp; Nakamura, Takashi; Crombrugghe, Benoit de

    2007-05-18

    We identified a cDNA encoding mouse Tenascin-W (TN-W) upregulated by bone morphogenetic protein (Bmp)2 in ATDC5 osteo-chondroprogenitors. In adult mice, TN-W was markedly expressed in bone. In mouse embryos, during endochondral bone formation TN-W was localized in perichondrium/periosteum, but not in trabecular and cortical bones. During bone fracture repair, cells in the newly formed perichondrium/periosteum surrounding the cartilaginous callus expressed TN-W. Furthermore, TN-W was detectable in perichondrium/periosteum of Runx2-null and Osterix-null embryos, indicating that TN-W is expressed in preosteoblasts. In CFU-F and -O cells, TN-W had no effect on initiation of osteogenesis of bone marrow cells, and in MC3T3-E1 osteoblastic cells TN-W inhibited cell proliferation and Col1a1 expression. In addition, TN-W suppressed canonical Wnt signaling which stimulates osteoblastic differentiation. Our results indicate that TN-W is a novel marker of preosteoblasts in early stage of osteogenesis, and that TN-W inhibits cell proliferation and differentiation of preosteoblasts mediated by canonical Wnt signaling.

  18. 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.

  19. 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. PMID:26075411

  20. Monocarboxylate Transporter-1 Is Required for Cell Death in Mouse Chondrocytic ATDC5 Cells Exposed to Interleukin-1β via Late Phase Activation of Nuclear Factor κB and Expression of Phagocyte-type NADPH Oxidase*

    PubMed Central

    Yoshimura, Kentaro; Miyamoto, Yoichi; Yasuhara, Rika; Maruyama, Toshifumi; Akiyama, Tomohito; Yamada, Atsushi; Takami, Masamichi; Suzawa, Tetsuo; Tsunawaki, Shoko; Tachikawa, Tetsuhiko; Baba, Kazuyoshi; Kamijo, Ryutaro

    2011-01-01

    Interleukin-1β (IL-1β) induces cell death in chondrocytes in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner. In this study, increased production of lactate was observed in IL-1β-treated mouse chondrocytic ATDC5 cells prior to the onset of their death. IL-1β-induced cell death in ATDC5 cells was suppressed by introducing an siRNA for monocarboxylate transporter-1 (MCT-1), a lactate transporter distributed in plasma and mitochondrial inner membranes. Mct-1 knockdown also prevented IL-1β-induced expression of phagocyte-type NADPH oxidase (NOX-2), an enzyme specialized for production of ROS, whereas it did not have an effect on inducible NO synthase. Suppression of IL-1β-induced cell death by Nox-2 siRNA indicated that NOX-2 is involved in cell death. Phosphorylation and degradation of inhibitor of κBα (IκBα) from 5 to 20 min after the addition of IL-1β was not affected by Mct-1 siRNA. In addition, IκBα was slightly decreased after 12 h of incubation with IL-1β, and the decrease was prominent after 36 h, whereas activation of p65/RelA was observed from 12 to 48 h after exposure to IL-1β. These changes were not seen in Mct-1-silenced cells. Forced expression of IκBα super repressor as well as treatment with the IκB kinase inhibitor BAY 11-7082 suppressed NOX-2 expression. Furthermore, Mct-1 siRNA lowered the level of ROS generated after 15-h exposure to IL-1β, whereas a ROS scavenger, N-acetylcysteine, suppressed both late phase degradation of IκBα and Nox-2 expression. These results suggest that MCT-1 contributes to NOX-2 expression via late phase activation of NF-κB in a ROS-dependent manner in ATDC5 cells exposed to IL-1β. PMID:21372137

  1. Monocarboxylate transporter-1 is required for cell death in mouse chondrocytic ATDC5 cells exposed to interleukin-1beta via late phase activation of nuclear factor kappaB and expression of phagocyte-type NADPH oxidase.

    PubMed

    Yoshimura, Kentaro; Miyamoto, Yoichi; Yasuhara, Rika; Maruyama, Toshifumi; Akiyama, Tomohito; Yamada, Atsushi; Takami, Masamichi; Suzawa, Tetsuo; Tsunawaki, Shoko; Tachikawa, Tetsuhiko; Baba, Kazuyoshi; Kamijo, Ryutaro

    2011-04-29

    Interleukin-1β (IL-1β) induces cell death in chondrocytes in a nitric oxide (NO)- and reactive oxygen species (ROS)-dependent manner. In this study, increased production of lactate was observed in IL-1β-treated mouse chondrocytic ATDC5 cells prior to the onset of their death. IL-1β-induced cell death in ATDC5 cells was suppressed by introducing an siRNA for monocarboxylate transporter-1 (MCT-1), a lactate transporter distributed in plasma and mitochondrial inner membranes. Mct-1 knockdown also prevented IL-1β-induced expression of phagocyte-type NADPH oxidase (NOX-2), an enzyme specialized for production of ROS, whereas it did not have an effect on inducible NO synthase. Suppression of IL-1β-induced cell death by Nox-2 siRNA indicated that NOX-2 is involved in cell death. Phosphorylation and degradation of inhibitor of κBα (IκBα) from 5 to 20 min after the addition of IL-1β was not affected by Mct-1 siRNA. In addition, IκBα was slightly decreased after 12 h of incubation with IL-1β, and the decrease was prominent after 36 h, whereas activation of p65/RelA was observed from 12 to 48 h after exposure to IL-1β. These changes were not seen in Mct-1-silenced cells. Forced expression of IκBα super repressor as well as treatment with the IκB kinase inhibitor BAY 11-7082 suppressed NOX-2 expression. Furthermore, Mct-1 siRNA lowered the level of ROS generated after 15-h exposure to IL-1β, whereas a ROS scavenger, N-acetylcysteine, suppressed both late phase degradation of IκBα and Nox-2 expression. These results suggest that MCT-1 contributes to NOX-2 expression via late phase activation of NF-κB in a ROS-dependent manner in ATDC5 cells exposed to IL-1β. PMID:21372137

  2. 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

  3. Histone Deacetylase 3 Depletion in Osteo/Chondroprogenitor Cells Decreases Bone Density and Increases Marrow Fat

    PubMed Central

    Casper, Michelle E.; McGee-Lawrence, Meghan E.; Stensgard, Bridget A.; Li, Xiaodong; Secreto, Frank J.; Knutson, Sarah K.; Hiebert, Scott W.; Westendorf, Jennifer J.

    2010-01-01

    Histone deacetylase (Hdac)3 is a nuclear enzyme that contributes to epigenetic programming and is required for embryonic development. To determine the role of Hdac3 in bone formation, we crossed mice harboring loxP sites around exon 7 of Hdac3 with mice expressing Cre recombinase under the control of the osterix promoter. The resulting Hdac3 conditional knockout (CKO) mice were runted and had severe deficits in intramembranous and endochondral bone formation. Calvarial bones were significantly thinner and trabecular bone volume in the distal femur was decreased 75% in the Hdac3 CKO mice due to a substantial reduction in trabecular number. Hdac3-CKO mice had fewer osteoblasts and more bone marrow adipocytes as a proportion of tissue area than their wildtype or heterozygous littermates. Bone formation rates were depressed in both the cortical and trabecular regions of Hdac3 CKO femurs. Microarray analyses revealed that numerous developmental signaling pathways were affected by Hdac3-deficiency. Thus, Hdac3 depletion in osterix-expressing progenitor cells interferes with bone formation and promotes bone marrow adipocyte differentiation. These results demonstrate that Hdac3 inhibition is detrimental to skeletal health. PMID:20628553

  4. 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. PMID:27050327

  5. R-spondin 2 facilitates differentiation of proliferating chondrocytes into hypertrophic chondrocytes by enhancing Wnt/β-catenin signaling in endochondral ossification.

    PubMed

    Takegami, Yasuhiko; Ohkawara, Bisei; Ito, Mikako; Masuda, Akio; Nakashima, Hiroaki; Ishiguro, Naoki; Ohno, Kinji

    2016-04-22

    Endochondral ossification is a crucial process for longitudinal growth of bones. Differentiating chondrocytes in growth cartilage form four sequential zones of proliferation, alignment into column, hypertrophy, and substitution of chondrocytes with osteoblasts. Wnt/β-catenin signaling is essential for differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. R-spondin 2 (Rspo2), a member of R-spondin family, is an agonist for Wnt signaling, but its role in chondrocyte differentiation remains unknown. Here we report that growth cartilage of Rspo2-knockout mice shows a decreased amount of β-catenin and increased amounts collagen type II (CII) and Sox9 in the abnormally extended proliferating zone. In contrast, expression of collagen type X (CX) in the hypertrophic zone remains unchanged. Differentiating chondrogenic ATDC5 cells, mimicking proliferating chondrocytes, upregulate Rspo2 and its putative receptor, Lgr5, in parallel. Addition of recombinant human Rspo2 to differentiating ATDC5 cells decreases expressions of Col2a1, Sox9, and Acan, as well as production of proteoglycans. In contrast, lentivirus-mediated knockdown of Rspo2 has the opposite effect. The effect of Rspo2 on chondrogenic differentiation is mediated by Wnt/β-catenin signaling, and not by Wnt/PCP or Wnt/Ca(2+) signaling. We propose that Rspo2 activates Wnt/β-catenin signaling to reduce Col2a1 and Sox9 and to facilitate differentiation of proliferating chondrocytes into hypertrophic chondrocytes in growth cartilage. PMID:27012200

  6. The effect of insulin-loaded chitosan particle-aggregated scaffolds in chondrogenic differentiation.

    PubMed

    Malafaya, Patrícia B; Oliveira, João T; Reis, Rui L

    2010-02-01

    Osteochondral defect repair requires a tissue engineering approach that aims at mimicking the physiological properties and structure of two different tissues (cartilage and bone) using a scaffold-cell construct. One ideal approach would be to engineer in vitro a hybrid material using a single-cell source. For that purpose, the scaffold should be able to provide the adequate biochemical cues to promote the selective but simultaneous differentiation of both tissues. In this work, attention was paid primarily to the chondrogenic differentiation by focusing on the development of polymeric systems that provide biomolecules release to induce chondrogenic differentiation. For that, different formulations of insulin-loaded chitosan particle-aggregated scaffolds were developed as a potential model system for cartilage and osteochondral tissue engineering applications using insulin as a potent bioactive substance known to induce chondrogenic differentiation. The insulin encapsulation efficiency was shown to be high with values of 70.37 +/- 0.8%, 84.26 +/- 1.76%, and 87.23 +/- 1.58% for loadings of 0.05%, 0.5%, and 5%, respectively. The in vitro release profiles were assessed in physiological conditions mimicking the cell culture procedures and quantified by Micro-BCA protein assay. Different release profiles were obtained that showed to be dependent on the initial insulin-loading percentage. Further, the effect on prechondrogenic ATDC5 cells was investigated for periods up to 4 weeks by studying the influence of these release systems on cell morphology, DNA and glycosaminoglycan content, histology, and gene expression of collagen types I and II, Sox-9, and aggrecan assessed by real-time polymerase chain reaction. When compared with control conditions (unloaded scaffolds cultured with the standard chondrogenic-inducing medium), insulin-loaded scaffolds upregulated the Sox-9 and aggrecan expression after 4 weeks of culture. From the overall results, it is reasonable to

  7. Microarray Analyses of Gene Expression during Chondrocyte Differentiation Identifies Novel Regulators of Hypertrophy

    PubMed Central

    James, Claudine G.; Appleton, C. Thomas G.; Ulici, Veronica; Underhill, T. Michael; Beier, Frank

    2005-01-01

    Ordered chondrocyte differentiation and maturation is required for normal skeletal development, but the intracellular pathways regulating this process remain largely unclear. We used Affymetrix microarrays to examine temporal gene expression patterns during chondrogenic differentiation in a mouse micromass culture system. Robust normalization of the data identified 3300 differentially expressed probe sets, which corresponds to 1772, 481, and 249 probe sets exhibiting minimum 2-, 5-, and 10-fold changes over the time period, respectively. GeneOntology annotations for molecular function show changes in the expression of molecules involved in transcriptional regulation and signal transduction among others. The expression of identified markers was confirmed by RT-PCR, and cluster analysis revealed groups of coexpressed transcripts. One gene that was up-regulated at later stages of chondrocyte differentiation was Rgs2. Overexpression of Rgs2 in the chondrogenic cell line ATDC5 resulted in accelerated hypertrophic differentiation, thus providing functional validation of microarray data. Collectively, these analyses provide novel information on the temporal expression of molecules regulating endochondral bone development. PMID:16135533

  8. Aberrant Calreticulin Expression in Articular Cartilage of Dio2 Deficient Mice

    PubMed Central

    Bomer, Nils; Cornelis, Frederique M. F.; Ramos, Yolande F. M.; den Hollander, Wouter; Lakenberg, Nico; van der Breggen, Ruud; Storms, Lies; Slagboom, P. Eline; Lories, Rik J. U.; Meulenbelt, Ingrid

    2016-01-01

    Objective To identify intrinsic differences in cartilage gene expression profiles between wild-type- and Dio2-/--mice, as a mechanism to investigate factors that contribute to prolonged healthy tissue homeostasis. Methods Previously generated microarray-data (Illumina MouseWG-6 v2) of knee cartilage of wild-type and Dio2 -/- -mice were re-analyzed to identify differential expressed genes independent of mechanical loading conditions by forced treadmill-running. RT-qPCR and western blot analyses of overexpression and knockdown of Calr in mouse chondro-progenitor cells (ATDC5) were applied to assess the direct effect of differential Calr expression on cartilage deposition. Results Differential expression analyses of articular cartilage of Dio2-/- (N = 9) and wild-type-mice (N = 11) while applying a cutoff threshold (P < 0.05 (FDR) and FC > |1,5|) resulted in 1 probe located in Calreticulin (Calr) that was found significantly downregulated in Dio2-/- mice (FC = -1.731; P = 0.044). Furthermore, overexpression of Calr during early chondrogenesis in ATDC5 cells leads to decreased proteoglycan deposition and corresponding lower Aggrecan expression, whereas knocking down Calr expression does not lead to histological differences of matrix composition. Conclusion We here demonstrate that the beneficial homeostatic state of articular cartilage in Dio2-/- mice is accompanied with significant lower expression of Calr. Functional analyses further showed that upregulation of Calr expression could act as an initiator of cartilage destruction. The consistent association between Calr and Dio2 expression suggests that enhanced expression of these genes facilitate detrimental effects on cartilage integrity. PMID:27163789

  9. Prostaglandin F2α receptor (FP) signaling regulates Bmp signaling and promotes chondrocyte differentiation

    PubMed Central

    Kim, Joohwee; Shim, Minsub

    2015-01-01

    Prostaglandins are a group of lipid signaling molecules involved in various physiological processes. In addition, prostaglandins have been implicated in the development and progression of diseases including cancer, cardiovascular disease, and arthritis. Prostaglandins exert their effects through the activation of specific G protein-coupled receptors (GPCRs). In this report, we examined the role of prostaglandin F2α receptor (FP) signaling as a regulator of chondrocyte differentiation. We found that FP expression was dramatically induced during the differentiation of chondrocytes and was up-regulated in cartilages. Forced expression of FP in ATDC5 chondrogenic cell line resulted in the increased expression of differentiation-related genes and increased synthesis of the extracellular matrix (ECM) regardless of the presence of insulin. Similarly, PGF2α treatment induced the expression of chondrogenic marker genes. In contrast, knockdown of endogenous FP expression suppressed the expression of chondrocyte marker genes and ECM synthesis. Organ culture of cartilage rudiments revealed that PGF2α induces chondrocyte hypertrophy. Additionally, FP overexpression increased the levels of Bmp-6, phospho-Smad1/5, and Bmpr1a, while knockdown of FP reduced expression of those genes. These results demonstrate that up-regulation of FP expression plays an important role in chondrocyte differentiation and modulates Bmp signaling. PMID:25499765

  10. 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

  11. 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. PMID:24712343

  12. 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

  13. 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

  14. Curcumin inhibits cellular condensation and alters microfilament organization during chondrogenic differentiation of limb bud mesenchymal cells.

    PubMed

    Kim, Dong Kyun; Kim, Song Ja; Kang, Shin Sung; Jin, Eun Jung

    2009-09-30

    Curcumin is a well known natural polyphenol product isolated from the rhizome of the plant Curcuma longa, anti-inflammatory agent for arthritis by inhibiting synthesis of inflammatory prostaglandins. However, the mechanisms by which curcumin regulates the functions of chondroprogenitor, such as proliferation, precartilage condensation, cytoskeletal organization or overall chondrogenic behavior, are largely unknown. In the present report, we investigated the effects and signaling mechanism of curcumin on the regulation of chondrogenesis. Treating chick limb bud mesenchymal cells with curcumin suppressed chondrogenesis by stimulating apoptotic cell death. It also inhibited reorganization of the actin cytoskeleton into a cortical pattern concomitant with rounding of chondrogenic competent cells and down-regulation of integrin beta1 and focal adhesion kinase (FAK) phosphorylation. Curcumin suppressed the phosphorylation of Akt leading to Akt inactivation. Activation of Akt by introducing a myristoylated, constitutively active form of Akt reversed the inhibitory actions of curcumin during chondrogenesis. In summary, for the first time, we describe biological properties of curcumin during chondrogenic differentiation of chick limb bud mesenchymal cells. Curcumin suppressed chondrogenesis by stimulating apoptotic cell death and down-regulating integrin-mediated reorganization of actin cytoskeleton via modulation of Akt signaling. PMID:19478554

  15. 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

  16. Differentiated Staffing.

    ERIC Educational Resources Information Center

    Scobey, Mary-Margaret, Ed.; Fiorino, A. John, Ed.

    This book is a collection of six articles that deal with the concept and the practice of differentiated staffing in education. Included in the collection are articles on the concept itself; on problems, prospects, and the practical implementation of the concept; staff differentiation in a multiunit school; and polemical aspects of differentiated…

  17. 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.

  18. Comparative Analysis of Osteogenic/Chondrogenic Differentiation Potential in Primary Limb Bud-Derived and C3H10T1/2 Cell Line-Based Mouse Micromass Cultures

    PubMed Central

    Takács, Roland; Matta, Csaba; Somogyi, Csilla; Juhász, Tamás; Zákány, Róza

    2013-01-01

    Murine micromass models have been extensively applied to study chondrogenesis and osteogenesis to elucidate pathways of endochondral bone formation. Here we provide a detailed comparative analysis of the differentiation potential of micromass cultures established from either BMP-2 overexpressing C3H10T1/2 cells or mouse embryonic limb bud-derived chondroprogenitor cells, using micromass cultures from untransfected C3H10T1/2 cells as controls. Although the BMP-2 overexpressing C3H10T1/2 cells failed to form chondrogenic nodules, cells of both models expressed mRNA transcripts for major cartilage-specific marker genes including Sox9, Acan, Col2a1, Snorc, and Hapln1 at similar temporal sequence, while notable lubricin expression was only detected in primary cultures. Furthermore, mRNA transcripts for markers of osteogenic differentiation including Runx2, Osterix, alkaline phosphatase, osteopontin and osteocalcin were detected in both models, along with matrix calcification. Although the adipogenic lineage-specific marker gene FABP4 was also expressed in micromass cultures, Oil Red O-positive cells along with PPARγ2 transcripts were only detected in C3H10T1/2-derived micromass cultures. Apart from lineage-specific marker genes, pluripotency factors (Nanog and Sox2) were also expressed in these models, reflecting on the presence of various mesenchymal lineages as well as undifferentiated cells. This cellular heterogeneity has to be taken into consideration for the interpretation of data obtained by using these models. PMID:23921684

  19. Comparative analysis of osteogenic/chondrogenic differentiation potential in primary limb bud-derived and C3H10T1/2 cell line-based mouse micromass cultures.

    PubMed

    Takács, Roland; Matta, Csaba; Somogyi, Csilla; Juhász, Tamás; Zákány, Róza

    2013-01-01

    Murine micromass models have been extensively applied to study chondrogenesis and osteogenesis to elucidate pathways of endochondral bone formation. Here we provide a detailed comparative analysis of the differentiation potential of micromass cultures established from either BMP-2 overexpressing C3H10T1/2 cells or mouse embryonic limb bud-derived chondroprogenitor cells, using micromass cultures from untransfected C3H10T1/2 cells as controls. Although the BMP-2 overexpressing C3H10T1/2 cells failed to form chondrogenic nodules, cells of both models expressed mRNA transcripts for major cartilage-specific marker genes including Sox9, Acan, Col2a1, Snorc, and Hapln1 at similar temporal sequence, while notable lubricin expression was only detected in primary cultures. Furthermore, mRNA transcripts for markers of osteogenic differentiation including Runx2, Osterix, alkaline phosphatase, osteopontin and osteocalcin were detected in both models, along with matrix calcification. Although the adipogenic lineage-specific marker gene FABP4 was also expressed in micromass cultures, Oil Red O-positive cells along with PPARγ2 transcripts were only detected in C3H10T1/2-derived micromass cultures. Apart from lineage-specific marker genes, pluripotency factors (Nanog and Sox2) were also expressed in these models, reflecting on the presence of various mesenchymal lineages as well as undifferentiated cells. This cellular heterogeneity has to be taken into consideration for the interpretation of data obtained by using these models. PMID:23921684

  20. 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.

  1. 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

  2. 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. PMID:25772257

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Quantum differential cryptanalysis

    NASA Astrophysics Data System (ADS)

    Zhou, Qing; Lu, Songfeng; Zhang, Zhigang; Sun, Jie

    2015-06-01

    In this paper, we propose a quantum version of the differential cryptanalysis which offers a quadratic speedup over the existing classical one and show the quantum circuit implementing it. The quantum differential cryptanalysis is based on the quantum minimum/maximum-finding algorithm, where the values to be compared and filtered are obtained by calling the quantum counting algorithm. Any cipher which is vulnerable to the classical differential cryptanalysis based on counting procedures can be cracked more quickly under this quantum differential attack.

  8. Differentiating Classroom Guidance

    ERIC Educational Resources Information Center

    Akos, Patrick; Cockman, Caroline R.; Strickland, Cindy A.

    2007-01-01

    To differentiate is to make different, distinct, or specialized (Costello, 1994). Differentiation has become popular in education as an instructional philosophy aimed at equitably meeting the learning needs of all students in the classroom. Differentiated planning and delivery of classroom guidance is also necessary for appropriate school…

  9. 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.

  10. 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…

  11. Strategies for Differentiating Curricula.

    ERIC Educational Resources Information Center

    Thomas, Ronald S.; And Others

    Concentrating on strategies for processing information, this guide provides a collection of models and techniques appropriate for differentiating the content and instructional procedures in the classroom, and is designed for use with intermediate academically talented students. The guide is divided into four sections--Differentiated Questioning,…

  12. Valuing Differentiated Instruction

    ERIC Educational Resources Information Center

    Benjamin, Amy

    2006-01-01

    It is not enough to declare that differentiated instruction is going to be the order of the day. It also is not enough to call in a consultant and have teachers listen to a presentation about product, process, and assessment paradigms. Differentiated instruction is a practice that grows out of certain values that are important in the way school…

  13. 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…

  14. 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.

  15. Increasing Participation through Differentiation

    ERIC Educational Resources Information Center

    Christenson, Bridget; Wager, Anita A.

    2012-01-01

    One of the many challenges teachers face is trying to differentiate instruction so all students have equal opportunities to participate, learn, and engage. To provide guidelines for differentiated instruction in mathematics, staff from the Madison Metropolitan School District in Wisconsin created a pedagogical framework for teaching called…

  16. Differential Moessbauer spectrometer

    SciTech Connect

    Kurinyi, Yu.A.; Grotov, Yu.D.

    1988-07-01

    A spectrometer is described that permits hardware differentiation of spectra with respect to the energy of gamma radiation, specimen temperature, etc. Differentiation is performed by secondary modulation of source motion with subsequent phase-sensitive detection at the harmonics. The spectrometer is CAMAC-compatible and permits simultaneous measurement of the first four harmonics.

  17. Automatic Differentiation Package

    Energy Science and Technology Software Center (ESTSC)

    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.

  18. 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.

  19. Differentiated Teacher Evaluation.

    ERIC Educational Resources Information Center

    Glatthorn, Allan A.; Holler, Richard L.

    1987-01-01

    Calvert County School District, Maryland, has developed a differentiated teacher evaluation system that promotes collaboration among supervisors and administrators in rating teacher performance. Methods involve informal observation, rating observation, and nonrating observation. Implementation is accompanied by extensive formative evaluation by…

  20. 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. PMID:26453839

  1. 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.

  2. Differential perturbations and D{sub {infinity}}-differential modules

    SciTech Connect

    Lapin, S V

    2001-12-31

    In the present paper the notions of a D{sub {infinity}}-differential and a D{sub {infinity}}-differential module are introduced, which are, respectively, homotopically invariant analogues of the differential and the chain complex. Basic homotopic properties of D{sub {infinity}}-differentials and D{sub {infinity}}-differential modules are established. The connection between the Gugenheim-Lambe-Stasheff theory of differential perturbations in homological algebra and the construction of a D{sub {infinity}}-differential module is considered.

  3. Cell Differentiation and Checkpoint

    PubMed Central

    Sancho, Sara Cuesta; Ouchi, Toru

    2015-01-01

    DNA damage is induced in many types of cells by internal and external cell stress. When DNA is damaged, DNA Damage Response (DDR) programs are activated to repair the DNA lesions in order to preserve genomic integrity and suppress subsequent malignant transformation. Among these programs is cell cycle checkpoint that ensures cell cycle arrest and subsequent repair of the damaged DNA, apoptosis and senescence in various phases of the cell cycle. Moreover, recent studies have established the cell differentiation checkpoint, the other type of the checkpoint that is specifically activated in the course of differentiation. We will discuss the evidences that support the link between DNA damage proteins and C2C12 cell differentiation. PMID:26998525

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Disorders of Sexual Differentiation.

    PubMed

    Boyd, Theonia K

    2010-09-01

    The term, disorders of sexual differentiation, broadly represents a disjunction between genotype and phenotype. Phenotype in turn can refer to external or internal genital development. Disorders of sexual differentiation are determined at conception insofar as (1) the abnormal genotype is the aberrant genetic product of fertilization at the chromosomal level or (2) the abnormal phenotype results from postfertilization errors in function at the gene level, somewhere along the pathway of transcription and translation. In either event, the error is genetic, whether or not sporadic or inherited, even if the pathways have yet to be fully elucidated for a given disorder. PMID:26839224

  9. 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…

  10. 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…

  11. Overshooting by differential heating

    NASA Astrophysics Data System (ADS)

    Andrássy, R.; Spruit, H. C.

    2015-06-01

    On the long nuclear time scale of stellar main-sequence evolution, even weak mixing processes can become relevant for redistributing chemical species in a star. We investigate a process of "differential heating", which occurs when a temperature fluctuation propagates by radiative diffusion from the boundary of a convection zone into the adjacent radiative zone. The resulting perturbation of the hydrostatic equilibrium causes a flow that extends some distance from the convection zone. We study a simplified differential-heating problem with a static temperature fluctuation imposed on a solid boundary. The astrophysically relevant limit of a high Reynolds number and a low Péclet number (high thermal diffusivity) turns out to be interestingly non-intuitive. We derive a set of scaling relations for the stationary differential heating flow. A numerical method adapted to a high dynamic range in flow amplitude needed to detect weak flows is presented. Our two-dimensional simulations show that the flow reaches a stationary state and confirm the analytic scaling relations. These imply that the flow speed drops abruptly to a negligible value at a finite height above the source of heating. We approximate the mixing rate due to the differential heating flow in a star by a height-dependent diffusion coefficient and show that this mixing extends about 4% of the pressure scale height above the convective core of a 10 M⊙ zero-age main sequence star. Appendix A is available in electronic form at http://www.aanda.org

  12. 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...

  13. Teacher-Initiated Differentiation

    ERIC Educational Resources Information Center

    Ensign, Jacque

    2012-01-01

    Elementary school teachers in Seattle, Washington, are encouraged to adapt differentiated instructional practices in math to accommodate the particular students in their own classrooms. Seattle Public Schools is a large, urban district serving 47,000 students who speak over a hundred languages. More than a third receive free or reduced lunch. The…

  14. 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…

  15. 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…

  16. 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.

  17. 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…

  18. Parametric Differentiation and Integration

    ERIC Educational Resources Information Center

    Chen, Hongwei

    2009-01-01

    Parametric differentiation and integration under the integral sign constitutes a powerful technique for calculating integrals. However, this topic is generally not included in the undergraduate mathematics curriculum. In this note, we give a comprehensive review of this approach, and show how it can be systematically used to evaluate most of the…

  19. 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,…

  20. 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…

  1. Differentiation of Childhood. Editorial.

    ERIC Educational Resources Information Center

    Childhood: A Global Journal of Child Research, 1999

    1999-01-01

    Argues that the social structure of postindustrial society represents a structural integration of all children but this institutionalization constructs divergent local structures, marginalization, and cultural and social differentiation. Suggests that childhood research requires an elaboration of the acting subject and the framework of structures…

  2. [Differential diagnosis of panniculitides].

    PubMed

    Böer-Auer, A

    2016-07-01

    Panniculitides are diseases of the subcutaneous tissue with heterogeneous etiology. They may develop consequent to infections, as a reaction to drugs, after thermal injury, as part of autoimmune diseases, in metabolic disorders or due to infectious organisms. The clinical presentation with subcutaneous nodules is often nonspecific. Moreover, the differentiation from vasculitides of medium-sized vessels can be clinically challenging. Microscopic examination of biopsy specimens is of high importance in the differential diagnosis of panniculitides. Histopathologically, panniculitides can be classified according to the predominantly infiltrated area in septal and lobular panniculitides and they can be separated from vasculitides of medium-sized vessels. Diagnostic difficulties arise from inadequate biopsy specimens and from lack of clinicopathological correlation. This article summarizes diagnostic criteria of frequent and clinically important panniculitides. PMID:27226115

  3. Differential optoacoustic absorption detector

    NASA Technical Reports Server (NTRS)

    Shumate, M. S. (Inventor)

    1978-01-01

    A differential optoacoustic absorption detector employed two tapered cells in tandem or in parallel. When operated in tandem, two mirrors were used at one end remote from the source of the beam of light directed into one cell back through the other, and a lens to focus the light beam into the one cell at a principal focus half way between the reflecting mirror. Each cell was tapered to conform to the shape of the beam so that the volume of one was the same as for the other, and the volume of each received maximum illumination. The axes of the cells were placed as close to each other as possible in order to connect a differential pressure detector to the cells with connecting passages of minimum length. An alternative arrangement employed a beam splitter and two lenses to operate the cells in parallel.

  4. 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.

  5. [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. PMID:26549687

  6. Fast differential thermal analysis.

    NASA Technical Reports Server (NTRS)

    Wunderlich, B.; Wolpert, S. M.

    1972-01-01

    A study is conducted of the limits of time-dependent differential thermal analysis (DTA). Applications of DTA to the hysteresis phenomena of glasses are also reported. The computation of DTA sample temperatures is discussed, giving attention to feasible heating rates, transient effects to be measured, and the simulation of DTA responses to changes in thermal diffusivity similar to hysteresis phenomena in glasses. The reproducibility of temperature recording is checked with zone-refined organic chemicals.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Conservation laws, differential identities, and constraints of partial differential equations

    NASA Astrophysics Data System (ADS)

    Zharinov, V. V.

    2015-11-01

    We consider specific cohomological properties such as low-dimensional conservation laws and differential identities of systems of partial differential equations (PDEs). We show that such properties are inherent to complex systems such as evolution systems with constraints. The mathematical tools used here are the algebraic analysis of PDEs and cohomologies over differential algebras and modules.

  13. 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.

  14. 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…

  15. 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

  16. 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.

  17. Pulsed differential pumping system

    SciTech Connect

    Antipov, G.N.; Bagautdinov, F.A.; Rybalov, S.V.

    1985-06-01

    A pulsed differential pumping system is described for extracting an electron beam from a shaping region at a pressure of 10/sup -5/ torr into a volume with a pressure of 10-100 torr. A fast valve is used with appropriate geometrical parameters to reduce the length of the outlet channel considerable while increasing its diameter. Test results are given. The pumping system has two sections which communicate one with the other and with the volume at the elevated pressure which is produced by gasdynamic nozzles.

  18. 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.

  19. 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

  20. 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.

  1. 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

  2. Retinal differentiation in Drosophila.

    PubMed

    Treisman, Jessica E

    2013-07-01

    Drosophila eye development has been extensively studied, due to the ease of genetic screens for mutations disrupting this process. The eye imaginal disc is specified during embryonic and larval development by the Pax6 homolog Eyeless and a network of downstream transcription factors. Expression of these factors is regulated by signaling molecules and also indirectly by growth of the eye disc. Differentiation of photoreceptor clusters initiates in the third larval instar at the posterior of the eye disc and progresses anteriorly, driven by the secreted protein Hedgehog. Within each cluster, the combined activities of Hedgehog signaling and Notch-mediated lateral inhibition induce and refine the expression of the transcription factor Atonal, which specifies the founding R8 photoreceptor of each ommatidium. Seven additional photoreceptors, followed by cone and pigment cells, are successively recruited by the signaling molecules Spitz, Delta, and Bride of sevenless. Combinations of these signals and of intrinsic transcription factors give each ommatidial cell its specific identity. During the pupal stages, rhodopsins are expressed, and the photoreceptors and accessory cells take on their final positions and morphologies to form the adult retina. Over the past few decades, the genetic analysis of this small number of cell types arranged in a repetitive structure has allowed a remarkably detailed understanding of the basic mechanisms controlling cell differentiation and morphological rearrangement. PMID:24014422

  3. 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.

  4. 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

  5. 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.

  6. Differential interference contrast tomography.

    PubMed

    Vishnyakov, Gennady; Levin, Gennady; Minaev, Vladimir; Latushko, Mikhail; Nekrasov, Nikolay; Pickalov, Valery

    2016-07-01

    We present a new approach to optical tomography of phase objects that is referred to as differential interference contrast tomography (DICT). The main feature of DICT is that the result of tomographic reconstruction is a 3D DIC image. This image is described by partial derivative of 3D refractive index distribution in one direction. The DICT setup consists of a lateral shearing phase-shifting interference microscope with low-coherent LED illumination. To create projections of the sample at various illumination angles, an angular scanning beam was used. 3D DIC tomograms of a white blood cell are presented. The comparison between the reconstructed DIC tomogram slices and the conventional DIC images of the same sample at the same depths are also represented. PMID:27367095

  7. 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.

  8. Travelling Waves of Cell Differentiation.

    PubMed

    Benmir, M; Bessonov, N; Boujena, S; Volpert, V

    2015-12-01

    The paper is devoted to modelling of cell differentiation in an initially homogeneous cell population. The mechanism which provides coexistence of two cell lineages in the initially homogeneous cell population is suggested. If cell differentiation is initiated locally in space in the population of undifferentiated cells, it can propagate as a travelling wave converting undifferentiated cells into differentiated ones. We suggest a model of this process which takes into account intracellular regulation, extracellular regulation and different cell types. They include undifferentiated cells and two types of differentiated cells. When a cell differentiates, its choice between two types of differentiated cells is determined by the concentrations of intracellular proteins. Differentiated cells can either stimulate differentiation into their own cell lineage or into another cell lineage. In the case of the positive feedback, only one lineage of differentiated cells will finally appear. In the case of negative feedback, both of them can coexist. In this case a periodic spatial pattern emerges behind the wave. PMID:26141967

  9. 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…

  10. Early Earth differentiation

    NASA Astrophysics Data System (ADS)

    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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. Staff Differentiation. An Annotated Bibliography.

    ERIC Educational Resources Information Center

    Marin County Superintendent of Schools, Corte Madera, CA.

    This annotated bibliography reviews selected literature focusing on the concept of staff differentiation. Included are 62 items (dated 1966-1970), along with a list of mailing addresses where copies of individual items can be obtained. Also a list of 31 staff differentiation projects receiving financial assistance from the U.S. Office of Education…

  16. Massey products in differential cohomology

    NASA Astrophysics Data System (ADS)

    Grady, Daniel

    We generalize Massey products to differential cohomology and relate these products to trivializations of higher bundles equipped with connection. The construction presented here is analogous to the construction of matric Massey products given by Peter May, but generalized to sheaves. We also prove a theorem regarding the refinement of the singular Massey product to differential cohomology.

  17. 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…

  18. 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

  19. Neuroendocrine differentiation in cervical carcinoma.

    PubMed Central

    Savargaonkar, P R; Hale, R J; Mutton, A; Manning, V; Buckley, C H

    1996-01-01

    AIMS: To examine neuroendocrine differentiation, as shown by chromogranin A (CGA) expression, in cervical carcinomas. METHODS: Sixty seven cervical carcinomas were studied and were classified as adenocarcinomas, adenosquamous carcinomas or squamous cell carcinomas based on the assessment of haematoxylin and eosin staining and stains for mucin. Where features of glandular differentiation were identified, sections were also stained for evidence of intestinal type mucin. CGA immunostaining was done and the results were graded on a three point scale: 0, + (1-5% of cells positive) and ++ (> 5% of cells positive). These findings were then analysed with respect to lymph node status, tumour differentiation and clinical outcome. RESULTS: There were 32 adenocarcinomas, 18 adenosquamous carcinomas and 17 squamous cell carcinomas. Positive staining was seen in 14 (20.9%) cases, of which four were strongly positive. All but one case were either adenocarcinomas or adenosquamous carcinomas. There was a trend for CGA positivity to be related to intestinal differentiation but this failed to reach statistical significance. No correlation could be demonstrated between CGA staining and lymph node status, tumour differentiation and clinical outcome. CONCLUSIONS: Neuroendocrine differentiation is common in cervical carcinomas where there is evidence of glandular differentiation. Whilst the numbers in this study are relatively small, the presence of neuroendocrine cells in otherwise typical carcinomas does not seem to have any association with clinical behaviour. Images PMID:8655680

  20. Signaling Pathways in Osteoclast Differentiation.

    PubMed

    Kim, Jung Ha; Kim, Nacksung

    2016-01-01

    Osteoclasts are multinucleated cells of hematopoietic origin that are responsible for the degradation of old bone matrix. Osteoclast differentiation and activity are controlled by two essential cytokines, macrophage colony-stimulating factor (M-CSF) and the receptor activator of nuclear factor-κB ligand (RANKL). M-CSF and RANKL bind to their respective receptors c-Fms and RANK to stimulate osteoclast differentiation through regulation of delicate signaling systems. Here, we summarize the critical or essential signaling pathways for osteoclast differentiation including M-CSF-c-Fms signaling, RANKL-RANK signaling, and costimulatory signaling for RANK. PMID:26865996

  1. Early Planetary Differentiation: Comparative Planetology

    NASA Technical Reports Server (NTRS)

    Jones, John H.

    2006-01-01

    We currently have extensive data for four different terrestrial bodies of the inner solar system: Earth, the Moon, Mars, and the Eucrite Parent Body [EPB]. All formed early cores; but all(?) have mantles with elevated concentrations of highly sidero-phile elements, suggestive of the addition of a late "veneer". Two appear to have undergone extensive differentiation consistent with a global magma ocean. One appears to be inconsistent with a simple model of "low-pressure" chondritic differentiation. Thus, there seems to be no single, simple paradigm for understand-ing early differentiation.

  2. 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)

  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. Creating a Differentiated Mathematics Classroom

    ERIC Educational Resources Information Center

    Strong, Richard; Thomas, Ed; Perini, Matthew; Silver, Harvey

    2004-01-01

    Student differences in learning mathematics are categorized under four different mathematical learning styles. The names of books providing examples on how mathematics teachers can differentiate their classroom instructions are mentioned.

  5. 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.

  6. 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.

  7. Differential diagnosis in pediatric radiology

    SciTech Connect

    Grunebaum, M.

    1986-01-01

    This work presents 415 tables of differential diagnosis applicable to pediatric radiology, emphasizing clinical presentation and the findings of conventional radiographs. The six chapters cover the respiratory, cardiovascular, urinary, gastrointestinal, and skeletal systems, and the head. The first few tables in each chapter cover major clinical signs, the next few deal with the newborn period only, and the remainder deal with radiographic differential diagnoses seen in children. An index and brief reference list complete the book.

  8. Gene amplification during myogenic differentiation

    PubMed Central

    Fischer, Ulrike; Ludwig, Nicole; Raslan, Abdulrahman; Meier, Carola; Meese, Eckart

    2016-01-01

    Gene amplifications are mostly an attribute of tumor cells and drug resistant cells. Recently, we provided evidence for gene amplifications during differentiation of human and mouse neural progenitor cells. Here, we report gene amplifications in differentiating mouse myoblasts (C2C12 cells) covering a period of 7 days including pre-fusion, fusion and post-fusion stages. After differentiation induction we found an increase in copy numbers of CDK4 gene at day 3, of NUP133 at days 4 and 7, and of MYO18B at day 4. The amplification process was accompanied by gamma-H2AX foci that are indicative of double stand breaks. Amplifications during the differentiating process were also found in primary human myoblasts with the gene CDK4 and NUP133 amplified both in human and mouse myoblasts. Amplifications of NUP133 and CDK4 were also identified in vivo on mouse transversal cryosections at stage E11.5. In the course of myoblast differentiation, we found amplifications in cytoplasm indicative of removal of amplified sequences from the nucleus. The data provide further evidence that amplification is a fundamental mechanism contributing to the differentiation process in mammalians. PMID:26760505

  9. Sumoylation differentially regulates Sp1 to control cell differentiation

    PubMed Central

    Gong, Lili; Ji, Wei-Ke; Hu, Xiao-Hui; Hu, Wen-Feng; Tang, Xiang-Cheng; Huang, Zhao-Xia; Li, Ling; Liu, Mugen; Xiang, Shi-Hua; Wu, Erxi; Woodward, Zachary; Liu, Yi-Zhi; Nguyen, Quan Dong; Li, David Wan-Cheng

    2014-01-01

    The mammalian small ubiquitin-like modifiers (SUMOs) are actively involved in regulating differentiation of different cell types. However, the functional differences between SUMO isoforms and their mechanisms of action remain largely unknown. Using the ocular lens as a model system, we demonstrate that different SUMOs display distinct functions in regulating differentiation of epithelial cells into fiber cells. During lens differentiation, SUMO1 and SUMO2/3 displayed different expression, localization, and targets, suggesting differential functions. Indeed, overexpression of SUMO2/3, but not SUMO1, inhibited basic (b) FGF-induced cell differentiation. In contrast, knockdown of SUMO1, but not SUMO2/3, also inhibited bFGF action. Mechanistically, specificity protein 1 (Sp1), a major transcription factor that controls expression of lens-specific genes such as β-crystallins, was positively regulated by SUMO1 but negatively regulated by SUMO2. SUMO2 was found to inhibit Sp1 functions through several mechanisms: sumoylating it at K683 to attenuate DNA binding, and at K16 to increase its turnover. SUMO2 also interfered with the interaction between Sp1 and the coactivator, p300, and recruited a repressor, Sp3 to β-crystallin gene promoters, to negatively regulate their expression. Thus, stable SUMO1, but diminishing SUMO2/3, during lens development is necessary for normal lens differentiation. In support of this conclusion, SUMO1 and Sp1 formed complexes during early and later stages of lens development. In contrast, an interaction between SUMO2/3 and Sp1 was detected only during the initial lens vesicle stage. Together, our results establish distinct roles of different SUMO isoforms and demonstrate for the first time, to our knowledge, that Sp1 acts as a major transcription factor target for SUMO control of cell differentiation. PMID:24706897

  10. 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.

  11. Discovering new points of differentiation.

    PubMed

    MacMillan, I C; McGrath, R G

    1997-01-01

    Most profitable strategies are built on differentiation: offering customers something they value that competitors don't have. But most companies concentrate only on their products or services. In fact, a company can differentiate itself every point where it comes in contact with its customers--from the moment customers realize they need a product or service to the time when they dispose of it. The authors believe that if companies open up their thinking to their customer's entire experience with a product or service--the consumption chain--they can uncover opportunities to position their offerings in ways that neither they nor their competitors though possible. The authors show how even a mundane product such as candles can be successfully differentiated. By analyzing its customers' experiences and exploring various options, Blyth Industries, for example, has grown from a $2 million U.S. candle manufacturer into a global candle and accessory business with nearly $500 million in sales and a market value of $1.2 billion. Finding ways to differentiate one's company is a skill that can be nurtured, the authors contend. In this Manager's Tool Kit, they have designed a two-part approach that can help companies continually identify new points of differentiation and develop the ability to generate successful differentiation strategies. "Mapping the Consumption Chain" captures the customer's total experience with a product or service. "Analyzing Your Customer's Experience" shows managers how directed brainstorming about each step in the consumption chain can elicit numerous ways to differentiate any offering. PMID:10168333

  12. Differential algebras without differentials: An easy C++ implementation

    SciTech Connect

    Michelotti, L.

    1989-03-01

    Automated differentiation can be motivated and explained rather plainly without any reference to infinitesimals or differentials whatsoever. We shall describe one possible approach in this paper. The method which we shall use will suggest its own implementation. However, FORTRAN is not the most natural language in which to carry it out. In the second section we shall describe an almost trivial implementation using C++. (Indeed, one of the motivations for writing this paper is to persuade militant FORTRAN extremists to invest the four or five days necessary to learn this powerful and easy language.) Take heed, however, that what we describe below is only a stripped-down implementation, written in three days, of differential algebra's most essential features; it is not as robust as and does not contain the battery of tools available in Berz's DA package, the product of a significant amount of work. 10 refs.

  13. 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

  14. Differentiation method for phase recovery

    NASA Astrophysics Data System (ADS)

    Özcan, Meriç

    2015-03-01

    Here we consider a derivative based method for phase recovery and demonstrate a numerical method that can be described as differentiate and cross multiply operation to obtain the phase gradient. This method uses quadrature phase data that is in sine and cosine form, which is a natural outcome many interferometric measurements including that of digital holographic reconstruction. Since the differentiation is performed on trigonometric functions which are discrete, it is shown that the method of differentiation and the sampling rate are important considerations especially for the noise corrupt signals. The method is initially developed for 1D phase signals, and then later extended to 2D. Noise performance of the method is also investigated, and it is shown that for extremely noisy signals the method can be adapted to an iteration routine which recovers the phase successfully. We present simulations and the experimental results which show the validity of the approach.

  15. 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.

  16. 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.

  17. 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...

  18. 5 CFR 532.511 - Environmental differentials.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 5 Administrative Personnel 1 2013-01-01 2013-01-01 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, 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...

  20. 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.

  1. Constructing Complexity for Differentiated Learning

    ERIC Educational Resources Information Center

    Little, Catherine A.; Hauser, Sherryl; Corbishley, Jeffrey

    2009-01-01

    Differentiated instruction requires that teachers pay attention to many differences among students, including their varied interests, learning styles, and ability and achievement levels. This article grew out of a study that explored how the challenge level of learning tasks is connected to behavior for students who show strong potential in…

  2. Vitamin D and Cardiac Differentiation.

    PubMed

    Kim, Irene M; Norris, Keith C; Artaza, Jorge N

    2016-01-01

    Calcitriol (1,25-dihydroxycholecalciferol or 1,25-D3) is the hormonally active metabolite of vitamin D. Experimental studies of vitamin D receptors and 1,25-D3 establish calcitriol to be a critical regulator of the structure and function of the heart. Clinical studies link vitamin D deficiency with cardiovascular disease (CVD). Emerging evidence demonstrates that calcitriol is highly involved in CVD-related signaling pathways, particularly the Wnt signaling pathway. Addition of 1,25-D3 to cardiomyocyte cells and examination of its effects on cardiomyocytes and mainly Wnt11 signaling allowed the specific characterization of the role of calcitriol in cardiac differentiation. 1,25-D3 is demonstrated to: (i) inhibit cell proliferation without promoting apoptosis; (ii) decrease expression of genes related to the regulation of the cell cycle; (iii) promote formation of cardiomyotubes; (iv) induce expression of casein kinase-1-α1, a negative regulator of the canonical Wnt signaling pathway; and (v) increase expression of noncanonical Wnt11, which has been recognized to induce cardiac differentiation during embryonic development and in adult cells. Thus, it appears that vitamin D promotes cardiac differentiation through negative modulation of the canonical Wnt signaling pathway and upregulation of noncanonical Wnt11 expression. Future work to elucidate the role(s) of vitamin D in cardiovascular disorders will hopefully lead to improvement and potentially prevention of CVD, including abnormal cardiac differentiation in settings such as postinfarction cardiac remodeling. PMID:26827957

  3. 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…

  4. 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…

  5. 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…

  6. 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…

  7. 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.)

  8. Differentiated Instruction in Small Schools

    ERIC Educational Resources Information Center

    Smit, Robbert; Humpert, Winfried

    2012-01-01

    Rural areas in the alpine regions suffer from dwindling student numbers. Differentiated instruction (DI) could help improve the teaching culture by allowing instructors to better adapt to heterogeneous student groups. At the beginning of a combined research and school improvement project, a survey of 162 teachers and 1180 students was conducted to…

  9. Differentiated Staffing: Expectations and Pitfalls.

    ERIC Educational Resources Information Center

    Barbee, Don

    Once a differentiated staffing pattern has been adopted--with the understanding that it is not a panacea--staff members have an obligation to minimize distinctions of rank and prevent organizational rigidity by contributing in role areas other than their own and sharing in decisionmaking. Teacher aides are not expected to be substitutes for…

  10. Ordinary Differential Equation System Solver

    Energy Science and Technology Software Center (ESTSC)

    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.

  11. 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

  12. 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…

  13. Differential Association and Marijuana Use.

    ERIC Educational Resources Information Center

    Griffin, Brenda S.; Griffin, Charles T.

    Edwin Sutherland's differential association theory was posited to explain all types of criminal or delinquent behavior. While research efforts have generally been confined to a focus on general criminal or delinquent behavior of the individual, it appears that the theory may also be applied to specific criminal or delinquent acts such as marijuana…

  14. Differentiated Staffing: The Second Generation.

    ERIC Educational Resources Information Center

    Mann, Peter B.

    This paper describes two approaches to differentiated staffing. The first approach involved reorganizing teacher staffing by creating a career ladder to permit hierarchical staffing without freezing faculty in positions that would limit growth, fix rewards, and destroy morale. The career ladder allowed the use of teachers and paraprofessionals in…

  15. 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

  16. MEK5 suppresses osteoblastic differentiation.

    PubMed

    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. PMID:25998381

  17. Differential invariants and operators of invariant differentiation of the projectable action of Lie groups

    NASA Astrophysics Data System (ADS)

    Goncharovskii, M. M.; Shirokov, I. V.

    2015-05-01

    We describe the relation between operators of invariant differentiation and invariant operators on orbits of Lie group actions. We propose a new effective method for finding differential invariants and operators of invariant differentiation and present examples.

  18. 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.

  19. 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.

  20. Differential Gene Expression in Glaucoma

    PubMed Central

    Jakobs, Tatjana C.

    2014-01-01

    In glaucoma, regardless of its etiology, retinal ganglion cells degenerate and eventually die. Although age and elevated intraocular pressure (IOP) are the main risk factors, there are still many mysteries in the pathogenesis of glaucoma. The advent of genome-wide microarray expression screening together with the availability of animal models of the disease has allowed analysis of differential gene expression in all parts of the eye in glaucoma. This review will outline the findings of recent genome-wide expression studies and discuss their commonalities and differences. A common finding was the differential regulation of genes involved in inflammation and immunity, including the complement system and the cytokines transforming growth factor β (TGFβ) and tumor necrosis factor α (TNFα). Other genes of interest have roles in the extracellular matrix, cell–matrix interactions and adhesion, the cell cycle, and the endothelin system. PMID:24985133

  1. 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)

  2. 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

  3. 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

  4. [Hypophysitis : Types and differential diagnosis].

    PubMed

    Saeger, W

    2016-05-01

    Inflammatory findings in the pituitary glands account for approximately 1 % of operations in the sellar region. Primary inflammation (e.g. lymphocytic and idiopathic granulomatous hypophysitis) have to be differentiated from secondary types (e.g. concomittant inflammation with Rathke's cleft cysts, craniopharyngiomas and germinomas) and involvement of the pituitary in generalized inflammation (IgG4-related disease, sarcoidosis and septicopyemia). Langerhans cell histiocytosis also has to be considered for the differential diagnostics. Lymphocytic hypophysitis shows lymphocytic infiltrations of varying density, predominantly of the T‑cell type. Granulomatous hypophysitis has the features of sarcoidosis and can only be diagnosed by exclusion of generalized sarcoidosis. Secondary hypophysitis has a mixed cell infiltration, especially by histiocytic infiltration and predominantly originates from ruptures or bleeding from Rathke's cleft cysts. The frequently very sparse remnants of cyst epithelium should be confirmed by pankeratin immunostaining. PMID:27103256

  5. 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

  6. How to Differentiate a Number

    NASA Astrophysics Data System (ADS)

    Ufnarovski, Victor; Ahlander, Bo

    2003-09-01

    We define the derivative of an integer to be the map sending every prime to 1 and satisfying the Leibnitz rule. The aim of the article is to consider the basic properties of this map and to show how to generalize the notion to the case of rational and arbitrary real numbers. We make some conjectures and find some connections with Goldbach's Conjecture and the Twin Prime Conjecture. Finally, we solve the easiest associated differential equations and calculate the generating function.

  7. 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

  8. 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.

  9. 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.

  10. 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. PMID:18285181

  11. 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

  12. 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.

  13. Holographic holes and differential entropy

    NASA Astrophysics Data System (ADS)

    Headrick, Matthew; Myers, Robert C.; Wien, Jason

    2014-10-01

    Recently it has been shown that the Bekenstein-Hawking entropy formula evaluated on certain closed surfaces in the bulk of a holographic spacetime has an interpretation as the differential entropy of a particular family of intervals (or strips) in the boundary theory [1, 2]. We first extend this construction to bulk surfaces which vary in time. We then give a general proof of the equality between the gravitational entropy and the differential entropy. This proof applies to a broad class of holographic backgrounds possessing a generalized planar symmetry and to certain classes of higher-curvature theories of gravity. To apply this theorem, one can begin with a bulk surface and determine the appropriate family of boundary intervals by considering extremal surfaces tangent to the given surface in the bulk. Alternatively, one can begin with a family of boundary intervals; as we show, the differential entropy then equals the gravitational entropy of a bulk surface that emerges from the intersection of the neighboring entanglement wedges, in a continuum limit.

  14. 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

  15. 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

  16. 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.

  17. Mortality differentials among Israeli men.

    PubMed Central

    Manor, O; Eisenbach, Z; Peritz, E; Friedlander, Y

    1999-01-01

    OBJECTIVES: This study examined differentials in mortality among adult Israeli men with respect to ethnic origin, marital status, and several measures of social status. METHODS: Data were based on a linkage of records from a 20% sample of the 1983 census to records of deaths occurring before the end of 1992. The study population included 72,527 men, and the number of deaths was 17,378. RESULTS: Differentials is mortality by origin show that mortality was higher among individuals of North African origin than among those of Asian and European origin. After allowance for several socioeconomic indicators, the excess mortality among North African Jews was eliminated. Substantial and consistent differences in mortality were found according to education, occupation, income, possession of a car, housing, and household amenities. Differentials among the elderly were markedly narrower than those among men younger than 70 years. CONCLUSIONS: Some sectors of Israeli society have higher risks of death than others, including, among the male population, these who are poor, less educated, unmarried, unskilled, out of the labor force, and of North African origin. PMID:10589307

  18. Vinculin Functions as Regulator of Chondrogenesis*

    PubMed Central

    Koshimizu, Takao; Kawai, Masanobu; Kondou, Hiroki; Tachikawa, Kanako; Sakai, Norio; Ozono, Keiichi; Michigami, Toshimi

    2012-01-01

    To identify the genes involved in chondrocytic differentiation, we applied gene trap mutagenesis to a murine mesenchymal chondrogenic cell line ATDC5 and isolated a clone in which the gene encoding vinculin was trapped. The trapped allele was assumed to express a fusion protein containing a truncated vinculin lacking the tail domain and the geo product derived from the trap vector. The truncated vinculin was suggested to exert a dominant negative effect. Impaired functioning of vinculin caused by gene trapping in ATDC5 cells or knockdown in primary chondrocytes resulted in the reduced expression of chondrocyte-specific genes, including Col2a1, aggrecan, and Col10a1. The expression of Runx2 also was suppressed by the dysfunctional vinculin. On the other hand, the expression of Sox9, encoding a key transcription factor for chondrogenesis, was retained. Knockdown of vinculin in metatarsal organ cultures impaired the growth of the explants and reduced the expression of Col2a1 and aggrecan. Gene trapping or knockdown of vinculin decreased the phosphorylation of ERK1/2 but increased that of Src homology 2 domain-containing tyrosine phosphatase 2 (SHP2) and Akt during chondrocytic differentiation, suggesting a disturbance of signaling by insulin-like growth factor I (IGF-I). Knockdown of vinculin in the metatarsal organ culture abrogated the IGF-I-induced growth and inhibited the up-regulation of Col2a1 and aggrecan expression by IGF-I. Loss of vinculin function in differentiating chondrocytes impaired the activation of the p38 MAPK pathway also, suggesting its involvement in the regulation of chondrogenesis by vinculin. Our results indicate a tissue-specific function of vinculin in cartilage whereby it controls chondrocytic differentiation. PMID:22416133

  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. Differential phase shift keyed signal resolver

    NASA Technical Reports Server (NTRS)

    Hopkins, P. M.; Wallingford, W. M. (Inventor)

    1974-01-01

    A differential phase shift keyed signal resolver resolves the differential phase shift in the incoming signal to determine the data content thereof overcoming phase uncertainty without requiring a transmitted reference signal.

  1. 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

  2. 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…

  3. 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…

  4. Differential spot-size focus servo

    NASA Technical Reports Server (NTRS)

    Milster, T. D.; Wang, M. S.; Froehlich, F. F.; Kann, J. L.; Treptau, J. P.; Erwin, K. E.

    1991-01-01

    We describe performance of a differential spot-size (wax-wane) focus servo. Crosstalk from the tracks are analyzed in the single detector and differential focus circuits. Magnitude of the crosstalk is reduced by a factor of three in the differential circuit. A false focus-error signal (FES) is present when the spot crosses sector marks at an angle.

  5. 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 Section 532.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a)...

  6. 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…

  7. Numerical Differentiation of Noisy, Nonsmooth Data

    DOE PAGESBeta

    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.

  8. 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,…

  9. 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 Section 532.511 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE REGULATIONS PREVAILING RATE SYSTEMS Premium Pay and Differentials § 532.511 Environmental differentials. (a)...

  10. 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…

  11. 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.

  12. 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.

  13. Differentiating causes of respiratory distress.

    PubMed

    Davis, Mark; Holliday, Jack

    2005-01-01

    Respiratory emergencies will continue to make up a large percentage of our EMS calls. Many of these conditions will be managed in the same fashion early on with a focus on oxygenation and adequate ventilation. Once the ABCs have been stabilized, use your assessment skills to create a differential diagnosis for respiratory distress. Once a field impression has been made, you can better direct a specific treatment. As always, follow your local treatment protocols established by your medical director. Practice your assessment skills and attend as much training as you can on airway and respiratory emergencies. PMID:15743124

  14. 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.

  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. [Differential display technique and its progress].

    PubMed

    Chi, Yan; Li, Shan-Shan; Ma, Xi; Jin, Tao; Zhou, Dong-Po

    2005-03-01

    Differential display technique is an important method to isolate differentially expressed gene. Comparing to other methods like representational difference analysis, suppression subtractive hybridization and serial analysis of gene expression, differential display technique is used in higher frequency. Since it was established in 1992, it has overcome many disadvantages and widened its practical fields through improvements and enhancements by global researchers. In this paper the principle and the main advantages and disadvantages of differential display technique were briefly introduced. Meanwhile, the four progressed aspects in designing primer, reducing false positives, identifying differentially expressed gene and techniques derived from DD were introduced in detail. PMID:15843364

  17. 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

  18. Differential polarization imaging. I. Theory.

    PubMed

    Kim, M; Keller, D; Bustamante, C

    1987-12-01

    A theory of differential polarization imaging is derived using Mueller calculus. It is shown that, for any arbitrary object, 16 images (in general different) can be obtained by combining different incident polarizations of light and measuring the specific polarization components transmitted or scattered by the object. These are called the Mueller images of the object. Mathematical expressions of these images for an object of arbitrary geometry are derived using classical vector diffraction theory and the paraxial and thin lens approximations. The object is described as a collection of point polarizable groups. The electromagnetic fields are calculated using the first Born-Approximation, but extension of the theory to higher-order approximations is shown to be straightforward. These expressions are obtained for the transmission, or bright-field, geometry, and the scattering, or dark-field, configuration. In both cases, the contributions of scattering, absorption, and background illumination to the Mueller images are characterized. The contributions of linear dichroism, circular dichroism, and linear and circular intensity differential scattering to certain Mueller images are established. It is shown that the Mueller images represent a complete two-dimensional mapping of the molecular anisotropy of the object. PMID:3427199

  19. Genetic differentiation of Jewish populations.

    PubMed

    Klitz, W; Gragert, L; Maiers, M; Fernandez-Viña, M; Ben-Naeh, Y; Benedek, G; Brautbar, C; Israel, S

    2010-12-01

    The Jewish diaspora can be viewed as a natural process in population dispersion and differentiation. We extend genetic studies on the Jewish diaspora to an analysis of human leukocyte antigen (HLA) haplotype distributions in the Jewish peoples, and show the value of this information for the design of Jewish marrow donor registries. HLA data from the Hadassah Bone Marrow Registry having parental country-of-origin information comprise samples of geographically discrete regions. We analyzed the HLA allele and haplotype frequencies for each national sample using population genetic and clustering methods. Population differentiation among diaspora populations was shown on the basis of HLA haplotype frequencies, including differences within the more recently diverged European groups. A method of haplotype and population clustering showed patterns of unique haplotype affinities associated with specific Jewish populations. The evidence showed that diaspora Jewish populations can be sorted into distinct clades of which the Ashkenazi are but one. Relationships among Jewish populations are interpretable in light of the historical record. We suggest that a major contributing factor to the genetic divergence between Jewish groups may have been admixture with local host populations, while, at the same time, threads of Eastern Mediterranean ancestry remain evident. PMID:20860586

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. Wavelet differential neural network observer.

    PubMed

    Chairez, Isaac

    2009-09-01

    State estimation for uncertain systems affected by external noises is an important problem in control theory. This paper deals with a state observation problem when the dynamic model of a plant contains uncertainties or it is completely unknown. Differential neural network (NN) approach is applied in this uninformative situation but with activation functions described by wavelets. A new learning law, containing an adaptive adjustment rate, is suggested to imply the stability condition for the free parameters of the observer. Nominal weights are adjusted during the preliminary training process using the least mean square (LMS) method. Lyapunov theory is used to obtain the upper bounds for the weights dynamics as well as for the mean squared estimation error. Two numeric examples illustrate this approach: first, a nonlinear electric system, governed by the Chua's equation and second the Lorentz oscillator. Both systems are assumed to be affected by external perturbations and their parameters are unknown. PMID:19674951

  5. 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

  6. Motor vehicle differential gear housing

    SciTech Connect

    Bitcon, L.L.

    1990-06-12

    This patent describes a motor vehicle differential gear housing. It comprises: a substantially box shaped casing having an interior and exterior defined by front, rear, top, bottom and two side panels, the front and rear panels each having an aperture, the apertures being at least partially in axial alignment; first bearing means cooperating with the apertures and demountably secured to each of the front and rear panels. The first bearing means is aligned coaxially with the aligned portions of the apertures; the side panels each having an opening, the openings being at least partially in axial alignment; axle support bearing housings aligned coaxially with the aligned portions of the openings on the side panels and threadedly mounted therein and adapted to have driving axles journaled in second bearing means in the bearing housings; and at least the front and rear panels being removably attached to the side panels.

  7. 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.

  8. Differentiation Therapy of Acute Myeloid Leukemia

    PubMed Central

    Gocek, Elzbieta; Marcinkowska, Ewa

    2011-01-01

    Acute Myeloid Leukemia (AML) is a predominant acute leukemia among adults, characterized by accumulation of malignantly transformed immature myeloid precursors. A very attractive way to treat myeloid leukemia, which is now called ‘differentiation therapy’, was proposed as in vitro studies have shown that a variety of agents stimulate differentiation of the cell lines isolated from leukemic patients. One of the differentiation-inducing agents, all-trans retinoic acid (ATRA), which can induce granulocytic differentiation in myeloid leukemic cell lines, has been introduced into clinics to treat patients with acute promyelocytic leukemia (APL) in which a PML-RARA fusion protein is generated by a t(15;17)(q22;q12) chromosomal translocation. Because differentiation therapy using ATRA has significantly improved prognosis for patients with APL, many efforts have been made to find alternative differentiating agents. Since 1,25-dihydroxyvitamin D3 (1,25D) is capable of inducing in vitro monocyte/macrophage differentiation of myeloid leukemic cells, clinical trials have been performed to estimate its potential to treat patients with AML or myelodysplastic syndrome (MDS). Unfortunately therapeutic concentrations of 1,25D can induce potentially fatal systemic hypercalcemia, thus limiting clinical utility of that compound. Attempts to overcome this problem have focused on the synthesis of 1,25D analogs (VDAs) which retain differentiation inducing potential, but lack its hypercalcemic effects. This review aims to discuss current problems and potential solutions in differentiation therapy of AML. PMID:24212816

  9. On the implementation of automatic differentiation tools.

    SciTech Connect

    Bischof, C. H.; Hovland, P. D.; Norris, B.; Mathematics and Computer Science; Aachen Univ. of Technology

    2008-01-01

    Automatic differentiation is a semantic transformation that applies the rules of differential calculus to source code. It thus transforms a computer program that computes a mathematical function into a program that computes the function and its derivatives. Derivatives play an important role in a wide variety of scientific computing applications, including numerical optimization, solution of nonlinear equations, sensitivity analysis, and nonlinear inverse problems. We describe the forward and reverse modes of automatic differentiation and provide a survey of implementation strategies. We describe some of the challenges in the implementation of automatic differentiation tools, with a focus on tools based on source transformation. We conclude with an overview of current research and future opportunities.

  10. 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)

  11. Transcriptional Control of Terminal Nephron Differentiation

    PubMed Central

    El-Dahr, Samir S.; Aboudehen, Karam; Saifudeen, Zubaida

    2008-01-01

    Terminal differentiation of epithelial cells into more specialized cell types is a critical step of organogenesis. Throughout the process of terminal differentiation, epithelial progenitors acquire or up-regulate expression of renal function genes and cease to proliferate, while expression of embryonic genes is repressed. This exquisite coordination of gene expression is accomplished by signaling networks and transcription factors which couple the external environment with the new functional demands of the cell. While there has been much progress in understanding the early steps involved in renal epithelial cell differentiation, a major gap remains in our knowledge of the factors that control the steps of terminal differentiation. A number of signaling molecules and transcription factors have been recently implicated in determining segmental nephron identity and functional differentiation. While some of these factors (the p53 gene family, HNF1β) promote the terminal epithelial differentiation fate, others (Notch, Brn-1, IRX, KLF4 and Foxi1) tend to regulate differentiation of specific nephron segments and individual cell types. This article summarizes current knowledge related to these transcription factors and discusses how diverse cellular signals are integrated to generate a transcriptional output during the process of terminal differentiation. Since these transcriptional processes are accompanied by profound changes in nuclear chromatin structure involving the genes responsible for creating and maintaining the differentiated cell phenotype, future studies should focus on identifying the nature of these epigenetic events and factors, how they are regulated temporally and spatially, and the chromatin environment they eventually reside in. PMID:18287399

  12. A broader perspective of sexual differentiation

    SciTech Connect

    Fiddler, M.; Pergament, E.

    1997-03-31

    Human sexual differentiation is customarily depicted as a series of embryonic events that lead to male and female gonadal development and differential hormone expression that have behavioral as well as biological outcomes. The salient components of these events are the differential expression of two hormones - testosterone and Muellerian inhibiting substance - and the SRY gene, regulating, in turn, the transcription of other genes and culminating in male differentiation. Sex determination, then, is generally described as initially proceeding down a path toward female development unless the bipotential, indifferent gonad is modified toward male development by genes on the Y chromosome. 28 refs.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. Differential diagnosis of leg ulcers.

    PubMed

    Pannier, F; Rabe, E

    2013-03-01

    Leg and foot ulcers are symptoms of very different diseases. The aim of this paper is to demonstrate the differential diagnosis of leg ulcers. The majority of leg ulcers occur in the lower leg or foot. In non-venous ulcers the localization in the foot area is more frequent. The most frequent underlying disease is chronic venous disease. In 354 leg ulcers, Koerber found 75.25% venous leg ulcers, 3.66% arterial leg ulcers, 14.66% ulcers of mixed venous and arterial origin and 13.5% vasculitic ulcers. In the Swedish population of Skaraborg, Nelzen found a venous origin in 54% of the ulcer patients. Each leg ulcer needs a clinical and anamnestic evaluation. Duplex ultrasound is the basic diagnostic tool to exclude vascular anomalies especially chronic venous and arterial occlusive disease. Skin biopsies help to find a correct diagnosis in unclear or non-healing cases. In conclusion, chronic venous disease is the most frequent cause of leg ulcerations. Because 25% of the population have varicose veins or other chronic venous disease the coincidence of pathological venous findings and ulceration is very frequent even in non-venous ulcerations. Leg ulcers without the symptoms of chronic venous disease should be considered as non-venous. PMID:23482536

  19. 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.

  20. Differential Roles of PML Isoforms.

    PubMed

    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

  1. 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

  2. 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…

  3. MACSYMA's symbolic ordinary differential equation solver

    NASA Technical Reports Server (NTRS)

    Golden, J. P.

    1977-01-01

    The MACSYMA's symbolic ordinary differential equation solver ODE2 is described. The code for this routine is delineated, which is of interest because it is written in top-level MACSYMA language, and may serve as a good example of programming in that language. Other symbolic ordinary differential equation solvers are mentioned.

  4. 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.)

  5. Symbolic Solution of Linear Differential Equations

    NASA Technical Reports Server (NTRS)

    Feinberg, R. B.; Grooms, R. G.

    1981-01-01

    An algorithm for solving linear constant-coefficient ordinary differential equations is presented. The computational complexity of the algorithm is discussed and its implementation in the FORMAC system is described. A comparison is made between the algorithm and some classical algorithms for solving differential equations.

  6. Differential thermal infrared imaging for environmental inspection

    NASA Astrophysics Data System (ADS)

    Merla, Arcangelo; Di Donato, Luigi; Di Fazio, Micaela; Greco, Pasquale; Rainone, Mario L.

    2014-01-01

    Aerial differential thermal imaging has been proposed to characterize the ground temperature distribution of two solid waste landfills. The differential approach permitted detection of regions with thermal abnormalities potentially associated with either biogas leakage and migration or improper landfill settlement and management. Methods, results, limits, and potentialities of the proposed approach are discussed.

  7. 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…

  8. 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.

  9. Modeling Projects in a Differential Equations Course.

    ERIC Educational Resources Information Center

    Claus-McGahan, Elly

    1998-01-01

    Discusses the value of student-designed, in-depth, modeling projects in a differential equations course and how to prepare students. Provides excerpts from worksheets, a list of computer software for Macintosh that can be used in teaching differential equations, and an annotated bibliography. (Author/ASK)

  10. 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…

  11. The "Silver Cup" of Differentiated Instruction.

    ERIC Educational Resources Information Center

    Kapusnick, Regina A.; Hauslein, Christine M.

    2001-01-01

    In inclusive classrooms, all students can learn more effectively if teachers adjust instruction for individual learning styles and needs. This paper describes: reasons to use differentiated instruction; the principles of differentiated instruction (based on the theory of multiple intelligences); instructional strategies (e.g., acceleration,…

  12. Tracking: Educational Differentiation or Defective Strategy

    ERIC Educational Resources Information Center

    Ansalone, George

    2010-01-01

    For almost a century, schools have assigned students to various groups or classes based on their perceived academic ability. Referred to as Tracking, in the United States, and Streaming, in England, this organizational differentiation very often results in unequal access to knowledge and the differential treatment of students. Proponents of…

  13. 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…

  14. 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)…

  15. Gifted Students' Perceptions of the Differentiated Curriculum

    ERIC Educational Resources Information Center

    Dobron, Kendra Hollern

    2011-01-01

    A differentiated curriculum for the gifted provides learning experiences that are challenging, interesting, satisfying, useful in the application to the real world, transferable to other disciplines and content areas, and allows for choice. While a differentiated curriculum is necessary for gifted learners, students' attitudes, opinions, and…

  16. Discussion of Issues in Differential Response

    ERIC Educational Resources Information Center

    Hughes, Ronald C.; Rycus, Judith S.

    2013-01-01

    In this article, the authors responded to nine commentaries by 17 contributors to their article, "Issues in Differential Response." The authors found that a majority of the respondents agreed with the major conclusions of "Issues in Differential Response." However, there were varying degrees of disagreement regarding the…

  17. 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…

  18. Differentiation through Learning-Style Responsive Strategies

    ERIC Educational Resources Information Center

    Lauria, Jennifer

    2010-01-01

    Many children are in dire need of differentiated instruction to support their unique learning needs. Differentiated instruction seeks to maximize each student's growth by recognizing that students have different ways of learning, different interests, different ways of responding to instruction, and preferred ways of learning or expressing…

  19. Four-phase differential phase shift resolver

    NASA Technical Reports Server (NTRS)

    Hopkins, P. M.; Wallingford, W. M.

    1973-01-01

    Two systems have been developed to resolve phase uncertainty without transmitting reference signals. In both methods signal is impressed on carrier as differential, rather than absolute, phase shift. At the receiver four-phase demodulation and logic process unambiguously resolves differential phase shift of input carrier.

  20. 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…

  1. 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…

  2. 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…

  3. 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.

  4. 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…

  5. Grading and Differentiation: Paradox or Good Practice?

    ERIC Educational Resources Information Center

    Tomlinson, Carol Ann

    2005-01-01

    Teachers often perceive an inherent conflict between "differentiated instruction," which emphasizes attention to variance in students' readiness levels, interests, and learning profiles, and "the grading system," which seems to indicate a sort of rigidity and standardization. This article examines key principles of quality differentiation and of…

  6. 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…

  7. A Teacher's Guide to Differentiating Instruction. Newsletter

    ERIC Educational Resources Information Center

    Center for Comprehensive School Reform and Improvement, 2007

    2007-01-01

    Differentiation is modified instruction that helps students with diverse academic needs and learning styles master the same challenging academic content. This month's newsletter examines the characteristics of differentiation and offers suggestions for how teachers can use it to improve student achievement. [This document was produced by The…

  8. 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…

  9. Identifying Possible Sources of Differential Functioning Using Differential Bundle Functioning with Polytomously Scored Data

    ERIC Educational Resources Information Center

    McCarty, F. A.; Oshima, T. C.; Raju, Nambury S.

    2007-01-01

    Oshima, Raju, Flowers, and Slinde (1998) described procedures for identifying sources of differential functioning for dichotomous data using differential bundle functioning (DBF) derived from the differential functioning of items and test (DFIT) framework (Raju, van der Linden, & Fleer, 1995). The purpose of this study was to extend the procedures…

  10. Microfabricated mechanical biosensor with inherently differential readout

    NASA Astrophysics Data System (ADS)

    Savran, C. A.; Burg, T. P.; Fritz, J.; Manalis, S. R.

    2003-08-01

    We report measurements with a micromachined mechanical biosensor that inherently suppresses background effects by producing a differential signal with respect to a reference. The sensor comprises two adjacent cantilevers with interdigitated fingers between them that allow interferometric detection of the differential, i.e., relative bending. We demonstrate that differential detection can efficiently suppress unspecific chemical effects that result in cantilever bending. We show that the differential deflection noise is up to an order of magnitude lower than the absolute deflection noise in the low-frequency range of 0.0003-1 Hz, where many types of biologically relevant reactions occur. We also demonstrate the sensor's applicability to biological receptor-ligand systems by reporting experimental results on direct differential detection of biotin-streptavidin binding.