A phase 2 trial of high dose lenalidomide in patients with relapsed/refractory higher-risk myelodysplastic syndromes and acute myeloid leukaemia with trilineage dysplasia.

PubMed

Zeidan, Amer M; Smith, B Douglas; Carraway, Hetty E; Gojo, Ivana; DeZern, Amy; Gore, Steven D

2017-01-01

Limited therapies exist for patients with refractory and relapsed (RR) higher-risk myelodysplastic syndromes (HR-MDS) and acute myeloid leukaemia with trilineage dysplasia (AML-TD). High dose (HD) lenalidomide (50 mg) has activity as frontline therapy in elderly AML but there is limited data in the RR setting. This phase II trial included patients with RR HR-MDS or AML-TD at 2 doses of lenalidomide (15 or 50 mg) on days 1-28 of 42-day cycles. The primary endpoint was response rate using the 2006 International Working Group criteria. Overall survival (OS) was estimated by Kaplan-Meier methods. Of 27 patients enrolled, 59% had HR-MDS and 31% AML-TD. No patient had isolated del5q; 41% had poor-risk karyotype. Of 9 patients treated at 15 mg, 56% completed ≥2 cycles with no responses. Of 18 patients treated at 50 mg, 39% completed ≥2 cycles and 11% responded but all experienced grade 3/4 neutropenic fever/infection. The 60-day mortality rate was 30%. Median OS was 114 days with 19% surviving ≥1 year. The study was terminated due to lack of robust clinical activity. In conclusion, lenalidomide at 15 mg is ineffective in RR myeloid malignancies. Continous high dosing schedules are poorly tolerated and minimally active. Further evaluation should be considered in upfront intensive chemotherapy-ineligible patients. © 2016 John Wiley & Sons Ltd.

In vitro mesenchymal trilineage differentiation and extracellular matrix production by adipose and bone marrow derived adult equine multipotent stromal cells on a collagen scaffold.

PubMed

Xie, Lin; Zhang, Nan; Marsano, Anna; Vunjak-Novakovic, Gordana; Zhang, Yanru; Lopez, Mandi J

2013-12-01

Directed differentiation of adult multipotent stromal cells (MSC) is critical for effective treatment strategies. This study was designed to evaluate the capability of equine MSC from bone marrow (BMSC) and adipose tissue (ASC) on a type I collagen (COLI) scaffold to undergo chondrogenic, osteogenic and adipogenic differentiation and form extracellular matrix (ECM) in vitro. Following determination of surface antigen expression, MSC were loaded into scaffolds in a perfusion bioreactor and loading efficiency was quantified. Cell-scaffold constructs were assessed after loading and 7, 14 and 21 days of culture in stromal or induction medium. Cell number was determined with DNA content, cell viability and spatial uniformity with confocal laser microscopy and cell phenotype and matrix production with light and scanning electron microscopy and mRNA levels. The MSC were positive for CD29 (>90 %), CD44 (>99 %), and CD105 (>60 %). Loading efficiencies were >70 %. The ASC and BMSC cell numbers on scaffolds were affected by culture in induction medium differently. Viable cells remained uniformly distributed in scaffolds for up to 21 days and could be directed to differentiate or to maintain an MSC phenotype. Micro- and ultrastructure showed lineage-specific cell and ECM changes. Lineage-specific mRNA levels differed between ASC and BMSC with induction and changed with time. Based on these results, equine ASC and BMSC differentiate into chondrogenic, osteogenic and adipogenic lineages and form ECM similarly on COLI scaffolds. The collected data supports the potential for equine MSC-COLI constructs to support diverse equine tissue formation for controlled biological studies.

Heavy metal staining, a comparative assessment of gadolinium chloride and osmium tetroxide for inner ear labyrinthine contrast enhancement using X-ray microtomography.

PubMed

Wong, Christopher C; Curthoys, Ian S; O'Leary, Stephen J; Jones, Allan S

2013-01-01

The use of both gadolinium chloride (GdCl(3)) and osmium tetroxide (OsO(4)) allowed for the visualization of the membranous labyrinth and other intralabyrinthine structures, at different intensities, as compared with the control sample. This initial comparison shows the advantages of GdCl(3) in radiological assessments and OsO(4) in more detailed anatomical studies and pathways of labyrinthine pathogenesis using X-ray microtomography (microCT). To assess an improved OsO(4) staining protocol and compare the staining affinities against GdCl(3). Guinea pig temporal bones were stained with either GdCl(3) (2% w/v) for 7 days or OsO(4) (2% w/v) for 3 days, and scanned in a microCT system. The post-scanned datasets were then assessed in a 3D rendering program. The enhanced soft tissue contrast as presented in the temporal bones stained with either GdCl(3) or OsO(4) allowed for the membranous labyrinth to be visualized throughout the whole specimen. GdCl(3)-stained specimens presented more defined contours of the bone profile in the radiographs, while OsO(4)-stained specimens provided more anatomical detail of individual intralabyrinthine structures, hence allowing spatial relationships to be visualized with ease in a 3D rendering context and 2D axial slice images.

Torsional Eye Movements Evoked by Unilateral Labyrinthine Galvanic Polarizations in the Squirrel Monkey

NASA Technical Reports Server (NTRS)

Minor, Lloyd B.; Tomko, David L.; Paige, Gary D.

1995-01-01

longer periods of current administration. This adaptation is manifested as a perstimulus return toward resting discharge and poststimulus after-response in the opposite direction (Goldberg et al., 1984; Minor and Goldberg, l991). Cathodal currents (with respect to the perilymphatic space of the vestibule) are excitatory whereas anodal currents are inhibitory. Horizontal eye movements evoked by unilateral galvanic polarizations administered through chronically implanted labyrinthine stimulating electrodes have been studied in alert squirrel monkeys (Minor and Goldberg, 1991). We sought to extend this analysis by recording three-dimensional eye movements during galvanic stimulation. As predicted based upon roughly equal stimulation of ampullary nerves innervating the vertical canals, a substantial torsional component to the nystagmus is noted. The trajectory of torsional slow phases and nystagmus profile after the polarization provide insight into the central mechanisms that influence these responses.

Placentation and fetal membrane development in the South American coati, Nasua nasua (Mammalia, Carnivora, Procyonidae)

PubMed Central

2014-01-01

Background Placental research in carnivores has concentrated on domestic species, which have zonary, labyrinthine placentas with an endotheliochorial barrier. Although the coati, Nasua nasua, is a widely distributed species in South America, data on the development of the placenta and the fetal membranes in this species are very sparse. Findings Four placentas from mid-gestation to near term were collected from wild individuals and were investigated based on gross morphology, histology, immunohistochemistry and electron microscopy. The available data support the concept that the ancestral condition of placentation in carnivores is phylogenetically characterized by a zonary and labyrinthine placental type with an endotheliochorial fetomaternal barrier, comprising extended epitheliochorial and haemochorial zones, such as hemophagous organs for iron supply and histiotrophe uptake and a yolk sac placenta. Conclusions Because of the foundational mechanisms that lead to the considerable complexity of fetomaternal contact zones in carnivores have not been studied, carnivores are interesting animal models for interhaemal barrier differentiation. PMID:24969476

Convergence of limb, visceral, and vertical semicircular canal or otolith inputs onto vestibular nucleus neurons

NASA Technical Reports Server (NTRS)

Jian, B. J.; Shintani, T.; Emanuel, B. A.; Yates, B. J.

2002-01-01

The major goal of this study was to determine the patterns of convergence of non-labyrinthine inputs from the limbs and viscera onto vestibular nucleus neurons receiving signals from vertical semicircular canals or otolith organs. A secondary aim was to ascertain whether the effects of non-labyrinthine inputs on the activity of vestibular nucleus neurons is affected by bilateral peripheral vestibular lesions. The majority (72%) of vestibular nucleus neurons in labyrinth-intact animals whose firing was modulated by vertical rotations responded to electrical stimulation of limb and/or visceral nerves. The activity of even more vestibular nucleus neurons (93%) was affected by limb or visceral nerve stimulation in chronically labyrinthectomized preparations. Some neurons received non-labyrinthine inputs from a variety of peripheral sources, including antagonist muscles acting at the same joint, whereas others received inputs from more limited sources. There was no apparent relationship between the spatial and dynamic properties of a neuron's responses to tilts in vertical planes and the non-labyrinthine inputs that it received. These data suggest that non-labyrinthine inputs elicited during movement will modulate the processing of information by the central vestibular system, and may contribute to the recovery of spontaneous activity of vestibular nucleus neurons following peripheral vestibular lesions. Furthermore, some vestibular nucleus neurons with non-labyrinthine inputs may be activated only during particular behaviors that elicit a specific combination of limb and visceral inputs.

Convergence of limb, visceral, and vertical semicircular canal or otolith inputs onto vestibular nucleus neurons.

PubMed

Jian, B J; Shintani, T; Emanuel, B A; Yates, B J

2002-05-01

The major goal of this study was to determine the patterns of convergence of non-labyrinthine inputs from the limbs and viscera onto vestibular nucleus neurons receiving signals from vertical semicircular canals or otolith organs. A secondary aim was to ascertain whether the effects of non-labyrinthine inputs on the activity of vestibular nucleus neurons is affected by bilateral peripheral vestibular lesions. The majority (72%) of vestibular nucleus neurons in labyrinth-intact animals whose firing was modulated by vertical rotations responded to electrical stimulation of limb and/or visceral nerves. The activity of even more vestibular nucleus neurons (93%) was affected by limb or visceral nerve stimulation in chronically labyrinthectomized preparations. Some neurons received non-labyrinthine inputs from a variety of peripheral sources, including antagonist muscles acting at the same joint, whereas others received inputs from more limited sources. There was no apparent relationship between the spatial and dynamic properties of a neuron's responses to tilts in vertical planes and the non-labyrinthine inputs that it received. These data suggest that non-labyrinthine inputs elicited during movement will modulate the processing of information by the central vestibular system, and may contribute to the recovery of spontaneous activity of vestibular nucleus neurons following peripheral vestibular lesions. Furthermore, some vestibular nucleus neurons with non-labyrinthine inputs may be activated only during particular behaviors that elicit a specific combination of limb and visceral inputs.

Morphomechanics of bacterial biofilms undergoing anisotropic differential growth

NASA Astrophysics Data System (ADS)

Zhang, Cheng; Li, Bo; Huang, Xiao; Ni, Yong; Feng, Xi-Qiao

2016-10-01

Growing bacterial biofilms exhibit a number of surface morphologies, e.g., concentric wrinkles, radial ridges, and labyrinthine networks, depending on their physiological status and nutrient access. We explore the mechanisms underlying the emergence of these greatly different morphologies. Ginzburg-Landau kinetic method and Fourier spectral method are integrated to simulate the morphological evolution of bacterial biofilms. It is shown that the morphological instability of biofilms is triggered by the stresses induced by anisotropic and heterogeneous bacterial expansion, and involves the competition between membrane energy and bending energy. Local interfacial delamination further enriches the morphologies of biofilms. Phase diagrams are established to reveal how the anisotropy and spatial heterogeneity of growth modulate the surface patterns. The mechanics of three-dimensional microbial morphogenesis may also underpin self-organization in other development systems and provide a potential strategy for engineering microscopic structures from bacterial aggregates.

Discovery of a stem-like multipotent cell fate.

PubMed

Paffhausen, Emily S; Alowais, Yasir; Chao, Cara W; Callihan, Evan C; Creswell, Karen; Bracht, John R

2018-01-01

Adipose derived stem cells (ASCs) can be obtained from lipoaspirates and induced in vitro to differentiate into bone, cartilage, and fat. Using this powerful model system we show that after in vitro adipose differentiation a population of cells retain stem-like qualities including multipotency. They are lipid (-), retain the ability to propagate, express two known stem cell markers, and maintain the capacity for trilineage differentiation into chondrocytes, adipocytes, and osteoblasts. However, these cells are not traditional stem cells because gene expression analysis showed an overall expression profile similar to that of adipocytes. In addition to broadening our understanding of cellular multipotency, our work may be particularly relevant to obesity-associated metabolic disorders. The adipose expandability hypothesis proposes that inability to differentiate new adipocytes is a primary cause of metabolic syndrome in obesity, including diabetes and cardiovascular disease. Here we have defined a differentiation-resistant stem-like multipotent cell population that may be involved in regulation of adipose expandability in vivo and may therefore play key roles in the comorbidities of obesity.

BMP2 repression and optimized culture conditions promote human bone marrow-derived mesenchymal stem cell isolation.

PubMed

Kay, Alasdair Gawain; Dale, Tina Patricia; Akram, Khondoker Mehedi; Mohan, Param; Hampson, Karen; Maffulli, Nicola; Spiteri, Monica A; El Haj, Alicia Jennifer; Forsyth, Nicholas Robert

2015-01-01

Human mesenchymal stem cells (hMSC) are multipotent progenitor cells. We propose the optimization of hMSC isolation and recovery using the application of a controlled hypoxic environment. We evaluated oxygen, glucose and serum in the recovery of hMSC from bone marrow (BMhMSC). Colony forming units-fibroblastic, cell numbers, tri-lineage differentiation, immunofluorescence and microarray were used to confirm and characterize BMhMSC. In an optimized (2% O(2), 4.5 g/l glucose and 5% serum) environment both colony forming units-fibroblastic (p = 0.01) and cell numbers (p = 0.0001) were enhanced over standard conditions. Transcriptional analysis identified differential expression of bone morphogenetic protein 2 (BMP2) and, putatively, chemokine (C-X-C motif) receptor 2 (CXCR2) signaling pathways. We have detailed a potential milestone in the process of refinement of the BMhMSC isolation process.

Serum-converted platelet lysate can substitute for fetal bovine serum in human mesenchymal stromal cell cultures.

PubMed

Mojica-Henshaw, Mariluz P; Jacobson, Pam; Morris, Julie; Kelley, Linda; Pierce, Jan; Boyer, Michael; Reems, Jo-Anna

2013-12-01

Fetal bovine serum (FBS) is commonly used as a serum supplement for culturing human mesenchymal stromal cells (hMSCs). However, human cells grown in FBS, especially for extended periods, risk potential exposure to bovine immunogenic proteins and infectious agents. To address this issue, we investigated the ability of a novel human platelet serum supplement to substitute for FBS in hMSC cultures. Platelet lysate-serum (PL-serum) was converted from platelet lysate-plasma (PL-plasma) that was manufactured from pooled platelet-rich plasma (PRP) apheresis units. Growth factor levels and the number of residual intact platelets in PL-serum and PL-plasma were compared with enzyme-linked immunosorbent assays and flow cytometry, respectively. Proliferation responses of hMSCs cultured in PL-serum, PL-plasma, or FBS were assessed with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, the immunophenotype of harvested hMSCs was evaluated by flow cytometry and tri-lineage differentiation potential was evaluated by assessing adipogenic, osteogenic and chondrogenic development. Selected growth factor levels in PL-serum were not significantly different from PL-plasma (P > 0.05). hMSC cultures supplemented with PL-serum had comparable growth kinetics to PL-plasma, and hMSC yields were consistently greater than with FBS. hMSCs harvested from cultures supplemented with PL-serum, PL-plasma or FBS had similar cell surface phenotypes and maintained tri-lineage differentiation potential. PL-serum, similar to PL-plasma, can substitute for FBS in hMSC cultures. Use of PL-serum, in contrast to PL-plasma, has an added advantage of not requiring addition of a xenogeneic source of heparin, providing a completely xeno-free culture medium. Copyright © 2013 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Generation of an induced pluripotent stem cell line from chorionic villi of a Turner syndrome spontaneous abortion.

PubMed

Parveen, Shagufta; Panicker, M M; Gupta, Pawan Kumar

2017-03-01

A major cause of spontaneous abortions is chromosomal abnormality of foetal cells. We report the generation of an induced pluripotent stem cell line from the fibroblasts isolated from chorionic villi of an early spontaneously aborted foetus with Turner syndrome. The Turner syndrome villus induced pluripotent stem cell line is transgene free, retains the original XO karyotype, expresses pluripotency markers and undergoes trilineage differentiation. This pluripotent stem cell model of Turner syndrome should serve as a tool to study the developmental abnormalities of foetus and placenta that lead to early embryo lethality and profound symptoms like infertility in 45 XO survivors. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Mesenchymal Stem Cells in Cardiology

PubMed Central

White, Ian A.; Sanina, Cristina; Balkan, Wayne; Hare, Joshua M.

2017-01-01

Cardiovascular disease (CVD) accounts for more deaths globally than any other single disease. There are on average 1.5 million episodes of myocardial infarction (heart attack) each year in the United States alone with roughly one third resulting in death. There is therefore a major need for developing new and effective strategies to promote cardiac repair. Intramyocardial transplantation of mesenchymal stem cells (MSCs) has emerged as a leading contender in the pursuit of clinical intervention and therapy. MSCs are potent mediators of cardiac repair and are therefore an attractive tool in the development of pre-clinical and clinical trials. MSCs are capable of secreting a large array of soluble factors, which have had demonstrated effects on pathogenic cardiac remolding, fibrosis, immune activation and cardiac stem cell proliferation within the damaged heart. MSCs are also capable of differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells, although the relative contribution of trilineage differentiation and paracrine effectors on cardiac repair remains the subject of active investigation. PMID:27236666

Generation of induced pluripotent stem cells from a Becker muscular dystrophy patient carrying a deletion of exons 45-55 of the dystrophin gene (CCMi002BMD-A-9 ∆45-55).

PubMed

Gowran, Aoife; Spaltro, Gabriella; Casalnuovo, Federica; Vigorelli, Vera; Spinelli, Pietro; Castiglioni, Elisa; Rovina, Davide; Paganini, Stefania; Di Segni, Marina; Gervasini, Cristina; Nigro, Patrizia; Pompilio, Giulio

2018-04-01

Becker muscular dystrophy (BMD) is a dystrophinopathy caused by mutations in the dystrophin gene on chromosome Xp21. BMD mutations result in truncated semi-functional dystrophin isoforms. Consequently, less severe clinical symptoms become apparent later in life compared to Duchenne muscular dystrophy. Dermal fibroblasts from a BMD patient were electroporated with episomal plasmids containing reprogramming factors to create the induced pluripotent stem cell line: CCMi002BMD-A-9 that showed pluripotent markers, were karyotypically normal and capable of trilineage differentiation. MLPA analyses performed on DNA extracted from CCMi002BMD-A-9 showed an in-frame deletion of exons 45 to 55 (CCMi002BMD-A-9 Δ45-55). Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

In vitro analysis of equine, bone marrow-derived mesenchymal stem cells demonstrates differences within age- and gender-matched horses.

PubMed

Carter-Arnold, J L; Neilsen, N L; Amelse, L L; Odoi, A; Dhar, M S

2014-09-01

Stem cell therapies are used routinely in equine practice. Most published reports characterise stem cells derived from younger horses; however, middle-aged horses are often in athletic performance, and experience degenerative medical conditions. Thus, mesenchymal stem cells (MSCs) from this group should be investigated. To describe differences in in vitro adherence, proliferation and potential for differentiation of equine bone marrow-derived MSCs (equine BMMSCs) harvested from middle-aged (10-13 years old) female donors. Descriptive study of stem cell characteristics. Equine BMMSCs from 6 horses were cultured in vitro and evaluated for viability, proliferation, osteogenesis, chondrogenesis, adipogenesis, cluster-of-differentiation markers and gene expression. Equine BMMSCs from all 6 donors demonstrated fibroblastic, cellular morphology, adherence to plastic and expression of cluster-of-differentiation markers. They varied in their rate of proliferation and trilineage differentiation. The equine BMMSCs of one of 6 donors demonstrated a higher rate of proliferation, enhanced ability for cell passaging and a more robust in vitro differentiation. Comparatively, equine BMMSCs from 2 donors demonstrated a lower rate of proliferation and lack of osteogenic and chondrogenic differentiation. The results of this study confirm that donor-to-donor variation in equine BMMSCs exists and this variation can be documented using in vitro assays. Subjective assessment suggests that the rate of proliferation tends to correlate with differentiation potential. © 2013 EVJ Ltd.

Mesenchymal Stem Cells Derived from Human Limbal Niche Cells

PubMed Central

Li, Gui-Gang; Zhu, Ying-Ting; Xie, Hua-Tao; Chen, Szu-Yu; Tseng, Scheffer C. G.

2012-01-01

Purpose. We investigated whether human limbal niche cells generate mesenchymal stem cells. Methods. Limbal niche cells were isolated from the limbal stroma by collagenase alone or following dispase removal of the limbal epithelium (D/C), and cultured on plastic in Dulbecco's modified Eagle's medium (DMEM) with 10% fetal bovine serum (FBS), or coated or three-dimensional Matrigel in embryonic stem cell medium with leukemia inhibitory factor and basic fibroblast growth factor. Expression of cell markers, colony-forming units-fibroblast, tri-lineage differentiation, and ability of supporting limbal epithelial stem/progenitor cells were compared to limbal residual stromal cells. Results. Stromal cells expressing angiogenesis markers were found perivascularly, subjacent to limbal basal epithelial cells, and in D/C and limbal residual stromal cells. When seeded in three-dimensional Matrigel, D/C but not limbal residual stromal cells yielded spheres of angiogenesis progenitors that stabilized vascular networks. Similar to collagenase-isolated cells, D/C cells could be expanded on coated Matrigel for more than 12 passages, yielding spindle cells expressing angiogenesis and mesenchymal stem cells markers, and possessing significantly higher colony-forming units-fibroblast and more efficient tri-lineage differentiation than D/C and limbal residual stromal cells expanded on plastic in DMEM with 10% FBS, of which both lost the pericyte phenotype while limbal residual stromal cells turned into myofibroblasts. Upon reunion with limbal epithelial stem/progenitor cells to form spheres, D/C cells expanded on coated Matrigel maintained higher expression of p63α and lower expression of cytokeratin 12 than those expanded on plastic in DMEM with 10% FBS, while spheres formed with human corneal fibroblasts expressed cytokeratin 12 without p63α. Conclusions. In the limbal stroma, cells subjacent to limbal basal epithelial cells serve as niche cells, and generate progenitors with

From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells.

PubMed

Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Abdel-Rahman, Engy A; Reda, Asmaa M; Ali, Sameh S; Khater, Sherry M; Ashamallah, Sylvia A; Ismail, Amani M; Ismail, Hossam El-Din A; El-Badri, Nagwa; Ghoneim, Mohamed A

2017-01-01

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion . BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine.

Characterization and Application of a Disposable Rotating Bed Bioreactor for Mesenchymal Stem Cell Expansion.

PubMed

Neumann, Anne; Lavrentieva, Antonina; Heilkenbrinker, Alexandra; Loenne, Maren; Kasper, Cornelia

2014-11-27

Recruitment of mesenchymal stromal cells (MSC) into the field of tissue engineering is a promising development since these cells can be expanded vivo to clinically relevant numbers and, after expansion, retain their ability to differentiate into various cell lineages. Safety requirements and the necessity to obtain high cell numbers without frequent subcultivation of cells raised the question of the possibility of expanding MSC in one-way (single-use) disposable bioreactors. In this study, umbilical cord-derived MSC (UC-MSC) were expanded in a disposable Z 2000 H bioreactor under dynamic conditions. Z was characterized regarding residence time and mixing in order to evaluate the optimal bioreactor settings, enabling optimal mass transfer in the absence of shear stress, allowing an reproducible expansion of MSC, while maintaining their stemness properties. Culture of the UC-MSC in disposable Z 2000 H bioreactor resulted in a reproducible 8-fold increase of cell numbers after 5 days. Cells were shown to maintain specific MSC surface marker expression as well as trilineage differentiation potential and lack stress-induced premature senescence.

The natural history of trilinear myelodysplastic syndrome and erythroleukemia.

PubMed

Michiels, J J; van der Meulen, J; Brederoo, P

1997-01-01

A case of Di Guglielmo's syndrome passed through the three stages of chronic erythromyelosis, erythroleukemia and acute myeloid leukemia (AML). According to the FAB classification the subsequent stages of this syndrome were refractory anemia (RA), RA with excess of blasts (RAEB), AML-M6, AML-M2 and undifferentiated AML-MO as the end-stage disease. Light- and electronmicroscopice findings on peripheral blood and bone marrow slides showed a pronounced trilineage myelodysplastic syndrome (MDS) during the RA, RAEB, AML-M6 and M2 phases of the disease, i.e. dysplastic erythropoiesis with PAS-positive erythroblasts, agranular and hypogranular neutrophils and dysplastic megakaryocytes. It is concluded that this case of Di Guglielmo's syndrome with chronic erythromyelosis, erythroleukemia and AML appears to be a continuum of trilineage MDS, AML-M6 and M2 with dyserythropoiesis which evolved into AML-M0.

Atmospheric Oxygen Inhibits Growth and Differentiation of Marrow-Derived Mouse Mesenchymal Stem Cells via a p53 Dependent Mechanism: Implications for Long-Term Culture Expansion

PubMed Central

Boregowda, Siddaraju; Krishnappa, Veena; Chambers, Jeremy; LoGrasso, Phillip V.; Lai, Wen-Tzu; Ortiz, Luis A.; Phinney, Donald G.

2013-01-01

Large scale expansion of human mesenchymal stem cells (MSCs) is routinely performed for clinical therapy. In contrast, developing protocols for large scale expansion of primary mouse MSCs has been more difficult due to unique aspects of rodent biology. Currently, established methods to isolate mouse MSCs select for rapidly dividing subpopulations that emerge from bone marrow cultures following long-term (months) expansion in atmospheric oxygen. Herein, we demonstrate that exposure to atmospheric oxygen rapidly induced p53, TOP2A and BAX expression and mitochondrial ROS generation in primary mouse MSCs resulting in oxidative stress, reduced cell viability and inhibition of cell proliferation. Alternatively, procurement and culture in 5% oxygen supported more prolific expansion of the CD45−ve/CD44+ve cell fraction in marrow, produced increased MSC yields following immuno-depletion, and supported sustained MSC growth resulting in a 2300-fold increase in cumulative cell yield by 4th passage. MSCs cultured in 5% oxygen also exhibited enhanced tri-lineage differentiation. The oxygen-induced stress response was dependent upon p53 since siRNA mediated knockdown of p53 in wild type cells or exposure of p53−/− MSCs to atmospheric oxygen failed to induce ROS generation, reduce viability, or arrest cell growth. These data indicate that long-term culture expansion of mouse MSCs in atmospheric oxygen selects for clones with absent or impaired p53 function, which allows cells to escape oxygen-induced growth inhibition. In contrast, expansion in 5% oxygen generates large numbers of primary mouse MSCs that retain sensitivity to atmospheric oxygen, and therefore a functional p53 protein, even after long-term expansion in vitro. PMID:22367737

Visualization of Middle Ear Ossicles in Elder Subjects with Ultra-short Echo Time MR Imaging.

PubMed

Naganawa, Shinji; Nakane, Toshiki; Kawai, Hisashi; Taoka, Toshiaki; Suzuki, Kojiro; Iwano, Shingo; Satake, Hiroko; Grodzki, David

2017-04-10

To evaluate the visualization of middle ear ossicles by ultra-short echo time magnetic resonance (MR) imaging at 3T in subjects over 50 years old. Sixty ears from 30 elder patients that underwent surgical or interventional treatment for neurovascular diseases were included (ages: 50-82, median age: 65; 10 men, 20 women). Patients received follow-up MR imaging including routine T 1 - and T 2 -weighted images, time-of-flight MR angiography, and ultra-short echo time imaging (PETRA, pointwise encoding time reduction with radial acquisition). All patients underwent computed tomography (CT) angiography before treatment. Thin-section source CT images were correlated with PETRA images. Scan parameters for PETRA were: TR 3.13, TE 0.07, flip angle 6 degrees, 0.83 × 0.83 × 0.83 mm resolution, 3 min 43 s scan time. Two radiologists retrospectively evaluated the visibility of each ossicular structure as positive or negative using PETRA images. The structures evaluated included the head of the malleus, manubrium of the malleus, body of the incus, long process of the incus, and the stapes. Signal intensity of the ossicles was classified as: between labyrinthine fluid and air, similar to labyrinthine fluid, between labyrinthine fluid and cerebellar parenchyma, or higher than cerebellar parenchyma. In all ears, the body of the incus was visible. The head of the malleus was visualized in 36/60 ears. The manubrium of the malleus and long process of the incus was visualized in 1/60 and 4/60 ears, respectively. The stapes were not visualized in any ear. Signal intensity of the visible structures was between labyrinthine fluid and air in all ears. The body of the incus was consistently visualized with intensity between air and labyrinthine fluid on PETRA images in aged subjects. Poor visualization of the manubrium of the malleus, long process of the incus, and the stapes limits clinical significance of middle ear imaging with current PETRA methods.

From Human Mesenchymal Stem Cells to Insulin-Producing Cells: Comparison between Bone Marrow- and Adipose Tissue-Derived Cells

PubMed Central

Abdel-Rahman, Engy A.; Reda, Asmaa M.; Ashamallah, Sylvia A.; Ismail, Amani M.; Ismail, Hossam El-Din A.; El-Badri, Nagwa

2017-01-01

The aim of this study is to compare human bone marrow-derived mesenchymal stem cells (BM-MSCs) and adipose tissue-derived mesenchymal stem cells (AT-MSCs), for their differentiation potentials to form insulin-producing cells. BM-MSCs were obtained during elective orthotopic surgery and AT-MSCs from fatty aspirates during elective cosmetics procedures. Following their expansion, cells were characterized by phenotyping, trilineage differentiation ability, and basal gene expression of pluripotency genes and for their metabolic characteristics. Cells were differentiated according to a Trichostatin-A based protocol. The differentiated cells were evaluated by immunocytochemistry staining for insulin and c-peptide. In addition the expression of relevant pancreatic endocrine genes was determined. The release of insulin and c-peptide in response to a glucose challenge was also quantitated. There were some differences in basal gene expression and metabolic characteristics. After differentiation the proportion of the resulting insulin-producing cells (IPCs), was comparable among both cell sources. Again, there were no differences neither in the levels of gene expression nor in the amounts of insulin and c-peptide release as a function of glucose challenge. The properties, availability, and abundance of AT-MSCs render them well-suited for applications in regenerative medicine. Conclusion. BM-MSCs and AT-MSCs are comparable regarding their differential potential to form IPCs. The availability and properties of AT-MSCs render them well-suited for applications in regenerative medicine. PMID:28584815

Evaluation of transport conditions for autologous bone marrow-derived mesenchymal stromal cells for therapeutic application in horses

PubMed Central

Espina, Miguel; Jülke, Henriette; Brehm, Walter; Ribitsch, Iris; Winter, Karsten

2016-01-01

Background. Mesenchymal stromal cells (MSCs) are increasingly used for clinical applications in equine patients. For MSC isolation and expansion, a laboratory step is mandatory, after which the cells are sent back to the attending veterinarian. Preserving the biological properties of MSCs during this transport is paramount. The goal of the study was to compare transport-related parameters (transport container, media, temperature, time, cell concentration) that potentially influence characteristics of culture expanded equine MSCs. Methods. The study was arranged in three parts comparing (I) five different transport containers (cryotube, two types of plastic syringes, glass syringe, CellSeal), (II) seven different transport media, four temperatures (4 °C vs. room temperature; −20 °C vs. −80 °C), four time frames (24 h vs. 48 h; 48 h vs. 72 h), and (III) three MSC concentrations (5 × 106, 10 × 106, 20 × 106 MSC/ml). Cell viability (Trypan Blue exclusion; percent and total number viable cell), proliferation and trilineage differentiation capacity were assessed for each test condition. Further, the recovered volume of the suspension was determined in part I. Each condition was evaluated using samples of six horses (n = 6) and differentiation protocols were performed in duplicates. Results. In part I of the study, no significant differences in any of the parameters were found when comparing transport containers at room temperature. The glass syringe was selected for all subsequent evaluations (highest recoverable volume of cell suspension and cell viability). In part II, media, temperatures, or time frames had also no significant influence on cell viability, likely due to the large number of comparisons and small sample size. Highest cell viability was observed using autologous bone marrow supernatant as transport medium, and “transport” at 4 °C for 24 h (70.6% vs. control group 75.3%); this was not significant. Contrary, viability was unacceptably low

Small vestibular schwannomas presenting with facial nerve palsy.

PubMed

Espahbodi, Mana; Carlson, Matthew L; Fang, Te-Yung; Thompson, Reid C; Haynes, David S

2014-06-01

To describe the surgical management and convalescence of two patients presenting with severe facial nerve weakness associated with small intracanalicular vestibular schwannomas (VS). Retrospective review. Two adult female patients presenting with audiovestibular symptoms and subacute facial nerve paralysis (House-Brackmann Grade IV and V). In both cases, post-contrast T1-weighted magnetic resonance imaging revealed an enhancing lesion within the internal auditory canal without lateral extension beyond the fundus. Translabyrinthine exploration demonstrated vestibular nerve origin of tumor, extrinsic to the facial nerve, and frozen section pathology confirmed schwannoma. Gross total tumor resection with VIIth cranial nerve preservation and decompression of the labyrinthine segment of the facial nerve was performed. Both patients recovered full motor function between 6 and 8 months after surgery. Although rare, small VS may cause severe facial neuropathy, mimicking the presentation of facial nerve schwannomas and other less common pathologies. In the absence of labyrinthine extension on MRI, surgical exploration is the only reliable means of establishing a diagnosis. In the case of confirmed VS, early gross total resection with facial nerve preservation and labyrinthine segment decompression may afford full motor recovery-an outcome that cannot be achieved with facial nerve grafting.

Amniotic fluid stem cells prevent follicle atresia and rescue fertility of mice with premature ovarian failure induced by chemotherapy.

PubMed

Xiao, Guan-Yu; Liu, I-Hsuan; Cheng, Chun-Chun; Chang, Chia-Chun; Lee, Yen-Hua; Cheng, Winston Teng-Kuei; Wu, Shinn-Chih

2014-01-01

Chemotherapy used to treat cancer may cause irreversible premature ovarian failure (POF). Of late, amniotic fluid stem cells (AFSCs) provide a novel source for regenerative medicine because of their primitive stage, low immunogenicity, and easy accessibility. In this study, we isolated AFSCs from transgenic mice that ubiquitously express enhanced green fluorescence protein (EGFP). These AFSCs exhibited morphologies, immunophenotypes, and mesoderm trilineage differentiation potentials similar to mesenchymal stem cells (MSCs). Further, AFSCs proliferated faster than MSCs and expressed OCT4, a marker for pluripotency. To investigate their potential in recovering fertility in POF model, AFSCs were transplanted into the ovaries of mice with POF six weeks post induction using chemotherapeutic drugs, busulfan and cyclophosphamide. AFSCs could rescue the reproductive ability of mice with POF by preventing follicle atresia and sustaining the healthy follicles. Notably, the transplanted AFSCs did not differentiate into granulosa and germline cells in vivo. After one month, the decreased numbers of transplanted AFSCs accompanied with the reduced beneficial effects indicated that the therapeutic efficacy were directly from AFSCs. These findings demonstrated the therapeutic effects of AFSCs and suggested the promise of AFSCs for treating infertility and POF caused by chemotherapy.

Isolation and Characterization of Canine Amniotic Membrane-Derived Multipotent Stem Cells

PubMed Central

Kim, Hyung-Sik; Kang, Kyung-Sun

2012-01-01

Recent studies have shown that amniotic membrane tissue is a rich source of stem cells in humans. In clinical applications, the amniotic membrane tissue had therapeutic effects on wound healing and corneal surface reconstruction. Here, we successfully isolated and identified multipotent stem cells (MSCs) from canine amniotic membrane tissue. We cultured the canine amniotic membrane-derived multipotent stem cells (cAM-MSCs) in low glucose DMEM medium. cAM-MSCs have a fibroblast-like shape and adhere to tissue culture plastic. We characterized the immunophenotype of cAM-MSCs by flow cytometry and measured cell proliferation by the cumulative population doubling level (CPDL). We performed differentiation studies for the detection of trilineage multipotent ability, under the appropriate culture conditions. Taken together, our results show that cAM-MSCs could be a rich source of stem cells in dogs. Furthermore, cAM-MSCs may be useful as a cell therapy application for veterinary regenerative medicine. PMID:23024756

Defined Essential 8™ Medium and Vitronectin Efficiently Support Scalable Xeno-Free Expansion of Human Induced Pluripotent Stem Cells in Stirred Microcarrier Culture Systems

PubMed Central

Badenes, Sara M.; Fernandes, Tiago G.; Cordeiro, Cláudia S. M.; Boucher, Shayne; Kuninger, David; Vemuri, Mohan C.; Diogo, Maria Margarida; Cabral, Joaquim M. S.

2016-01-01

Human induced pluripotent stem (hiPS) cell culture using Essential 8™ xeno-free medium and the defined xeno-free matrix vitronectin was successfully implemented under adherent conditions. This matrix was able to support hiPS cell expansion either in coated plates or on polystyrene-coated microcarriers, while maintaining hiPS cell functionality and pluripotency. Importantly, scale-up of the microcarrier-based system was accomplished using a 50 mL spinner flask, under dynamic conditions. A three-level factorial design experiment was performed to identify optimal conditions in terms of a) initial cell density b) agitation speed, and c) to maximize cell yield in spinner flask cultures. A maximum cell yield of 3.5 is achieved by inoculating 55,000 cells/cm2 of microcarrier surface area and using 44 rpm, which generates a cell density of 1.4x106 cells/mL after 10 days of culture. After dynamic culture, hiPS cells maintained their typical morphology upon re-plating, exhibited pluripotency-associated marker expression as well as tri-lineage differentiation capability, which was verified by inducing their spontaneous differentiation through embryoid body formation, and subsequent downstream differentiation to specific lineages such as neural and cardiac fates was successfully accomplished. In conclusion, a scalable, robust and cost-effective xeno-free culture system was successfully developed and implemented for the scale-up production of hiPS cells. PMID:26999816

Manipulation of arousal and its effects on human vestibular nystagmus induced by caloric irrigation and angular accelerations.

DOT National Transportation Integrated Search

1962-10-01

Alterations in the nystagmic reaction of human subjects exposed to vestibular stimulation have been frequently noted in studies of drug effects, habituation, and general features of the labyrinthine response.

Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin.

PubMed

Seo, Aaron; Ben-Harosh, Miri; Sirin, Mehtap; Stein, Jerry; Dgany, Orly; Kaplelushnik, Joseph; Hoenig, Manfred; Pannicke, Ulrich; Lorenz, Myriam; Schwarz, Klaus; Stockklausner, Clemens; Walsh, Tom; Gulsuner, Suleyman; Lee, Ming K; Sendamarai, Anoop; Sanchez-Bonilla, Marilyn; King, Mary-Claire; Cario, Holger; Kulozik, Andreas E; Debatin, Klaus-Michael; Schulz, Ansgar; Tamary, Hannah; Shimamura, Akiko

2017-08-17

We report 5 individuals in 3 unrelated families with severe thrombocytopenia progressing to trilineage bone marrow failure (BMF). Four of the children received hematopoietic stem cell transplants and all showed poor graft function with persistent severe cytopenias even after repeated transplants with different donors. Exome and targeted sequencing identified mutations in the gene encoding thrombopoietin ( THPO ): THPO R99W, homozygous in affected children in 2 families, and THPO R157X, homozygous in the affected child in the third family. Both mutations result in a lack of THPO in the patients' serum. For the 2 surviving patients, improvement in trilineage hematopoiesis was achieved following treatment with a THPO receptor agonist. These studies demonstrate that biallelic loss-of-function mutations in THPO cause BMF, which is unresponsive to transplant due to a hematopoietic cell-extrinsic mechanism. These studies provide further support for the critical role of the MPL-THPO pathway in hematopoiesis and highlight the importance of accurate genetic diagnosis to inform treatment decisions for BMF. © 2017 by The American Society of Hematology.

Effects of optokinetic stimulation induced by virtual reality on locomotion: a preliminary study.

PubMed

Ohyama, Seizo; Nishiike, Suetaka; Watanabe, Hiroshi; Matsuoka, Katsunori; Takeda, Noriaki

2008-11-01

Exposure to a virtual environment for 20 min was sufficient to cause adaptive changes in locomotion in healthy subjects, suggesting that virtual environments might improve locomotor deviation in patients with unilateral labyrinthine defects. Postural and locomotor control in patients with unilateral labyrinthine defects deviates towards the lesion side. The aim of this study was to examine whether active locomotion within a virtual environment can increase the functionality of rehabilitation. We examined the effects of optokinetic stimulation produced by a virtual reality environment on ocular movement and locomotor tracks in 10 healthy subjects. During the 20 min experiment, the mean locomotor deviation and the mean frequency and mean amplitude of optokinetic nystagmus during the last period of the experiment were significantly higher than those during the initial period.

Tympanometric findings in superior semicircular canal dehiscence syndrome.

PubMed

Castellucci, A; Brandolini, C; Piras, G; Modugno, G C

2013-04-01

The diagnostic role of audio-impedancemetry in superior semicircular canal dehiscence (SSCD) disease is well known. In particular, since the first reports, the presence of evoked acoustic reflexes has represented a determining instrumental exhibit in differential diagnosis with other middle ear pathologies that are responsible for a mild-low frequencies air-bone gap (ABG). Even though high resolution computed tomography (HRCT) completed by parasagittal reformatted images still represents the diagnostic gold standard, several instrumental tests can support a suspect of labyrinthine capsule dehiscence when "suggestive" symptoms occur. Objective and subjective audiometry often represents the starting point of the diagnostic course aimed at investigating the cause responsible for the so-called "intra-labyrinthine conductive hearing loss". The purpose of this study is to evaluate the role of tympanometry, in particular of the inter-aural asymmetry ratio in peak compliance as a function of different mild-low frequencies ABG on the affected side, in the diagnostic work-up in patients with unilateral SSCD. The working hypothesis is that an increase in admittance of the "inner-middle ear" conduction system due to a "third mobile window" could be detected by tympanometry. A retrospective review of the clinical records of 45 patients with unilateral dehiscence selected from a pool of 140 subjects diagnosed with SSCD at our institution from 2003 to 2011 was performed. Values of ABG amplitude on the dehiscent side and tympanometric measurements of both ears were collected for each patient in the study group (n = 45). An asymmetry between tympanometric peak compliance of the involved side and that of the contralateral side was investigated by calculating the inter-aural difference and the asymmetry ratio of compliance at the eardrum. A statistically significant correlation (p = 0.015 by Fisher's test) between an asymmetry ratio ≥ 14% in favour of the pathologic ear and an ABG

Labyrinthine flows across multilayer graphene-based membranes

NASA Astrophysics Data System (ADS)

Yoshida, Hiroaki

Graphene-based materials have recently found extremely wide applications for fluidic purposes thanks to remarkable developments in micro-/nano-fabrication techniques. In particular, high permeability and specific selectivity have been reported for these graphene-based membranes, such as the graphene-oxide membranes, with however controversial experimental results. There is therefore an urgent need to propose a theoretical framework of fluid transport in these architectures in order to rationalize the experimental results.In this presentation, we report a theoretical study of mass transport across multilayer graphene based membranes, which we benchmark by atomic-scale molecular dynamics. Specifically, we consider the water flow across multiple graphene layers with an inter-layer distance ranging from sub-nanometer to a few nanometers. The graphene layers have nanoslits aligned in a staggered fashion, and thus the water flows involve multiple twists and turns. We compare the continuum model predictions for the permeability with the lattice Boltzmann calculations and molecular dynamics simulations. The highlight is that, in spite of extreme confinement, the permeability across the graphene-based membrane is quantitatively predicted on the basis of a properly designed continuum model. The framework of this study constitutes a benchmark to which we compare favourably published experimental data.In addition, flow properties of a water-ethanol mixture are presented, demonstrating the possibility of a novel separation technique. While the membrane is permeable to both pure liquids, it exhibits a counter-intuitive ``self-semi-permeability'' to water in the presence of the mixture. This suggests a robust and versatile membrane-based separation method built on a pressure-driven reverse-osmosis process, which is considerably less energy consuming than distillation processes. The author acknowledges the ERC project Micromegas and the ANR projects BlueEnergy and Equip@Meso.

Broadband high sound absorption from labyrinthine metasurfaces

NASA Astrophysics Data System (ADS)

Chang, Huiting; Liu, Liu; Zhang, Chi; Hu, Xinhua

2018-04-01

Metamaterials are artificial structures which exhibit fascinating properties unreachable by traditional materials. Here, we report on the design, fabrication, and characterization of acoustic metasurfaces consisting of dead-end channels coiled in a 2D plane. It is found that when the area of the channel's cross section is about 1/10 of the area (4.3 cm × 4.3 cm) of the upper surface of the building block, the sound loss in channels approaches to a critical value, resulting in near-perfect absorption (A > 99%) at resonant frequency. When the building block contains ten channels with specially designed lengths, sound waves can be highly absorbed above a cutoff frequency fc (A > 90% for fc < f < 3fc). The wavelength at the cutoff frequency can be 7.1 times of the thickness of the metasurface. Our results could find applications in noise reduction and sound detection.

Equine bone marrow-derived mesenchymal stromal cells are heterogeneous in MHC class II expression and capable of inciting an immune response in vitro

PubMed Central

2014-01-01

Introduction The horse is a valuable species to assess the effect of allogeneic mesenchymal stromal cells (MSCs) in regenerative treatments. No studies to date have examined recipient response to major histocompatibility complex (MHC)-mismatched equine MSCs. The purposes of this study were to immunophenotype MSCs from horses of known MHC haplotype and to compare the immunogenicity of MSCs with differing MHC class II expression. Methods MSCs and peripheral blood leukocytes (PBLs) were obtained from Thoroughbred horses (n = 10) of known MHC haplotype (ELA-A2, -A3, and -A9 homozygotes). MSCs were cultured through P8; cells from each passage (P2 to P8) were cryopreserved until used. Immunophenotyping of MHC class I and II, CD44, CD29, CD90, LFA-1, and CD45RB was performed by using flow cytometry. Tri-lineage differentiation assays were performed to confirm MSC multipotency. Recombinant equine IFN-γ was used to stimulate MHC class II negative MSCs in culture, after which expression of MHC class II was re-examined. To assess the ability of MHC class II negative or positive MSCs to stimulate an immune response, modified one-way mixed leukocyte reactions (MLRs) were performed by using MHC-matched and mismatched responder PBLs and stimulator PBLs or MSCs. Proliferation of gated CFSE-labeled CD3+ responder T cells was evaluated via CFSE attenuation by using flow cytometry and reported as the number of cells in the proliferating T-cell gate. Results MSCs varied widely in MHC class II expression despite being homogenous in terms of “stemness” marker expression and ability to undergo trilineage differentiation. Stimulation of MHC class II negative MSCs with IFN-γ resulted in markedly increased expression of MHC class II. MLR results revealed that MHC-mismatched MHC class II-positive MSCs caused significantly increased responder T-cell proliferation compared with MHC-mismatched MHC class II-negative and MHC-matched MSCs, and equivalent to that of the positive control of

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.

Emergent Rotational Symmetries in Disordered Magnetic Domain Patterns

NASA Astrophysics Data System (ADS)

Su, Run; Seu, Keoki A.; Parks, Daniel; Kan, Jimmy J.; Fullerton, Eric E.; Roy, Sujoy; Kevan, Stephen D.

2011-12-01

Uniaxial systems often form labyrinthine domains that exhibit short-range order but are macroscopically isotropic and would not be expected to exhibit precise symmetries. However, their underlying frustration results in a multitude of metastable configurations of comparable energy, and driving such a system externally might lead to pattern formation. We find that soft x-ray speckle diffraction patterns of the labyrinthine domains in CoPd/IrMn heterostructures reveal a diverse array of hidden rotational symmetries about the magnetization axis, thereby suggesting an unusual form of emergent order in an otherwise disordered system. These symmetries depend on applied magnetic field, magnetization history, and scattering wave vector. Maps of rotational symmetry exhibit intriguing structures that can be controlled by manipulating the applied magnetic field in concert with the exchange bias condition.

Emergent rotational symmetries in disordered magnetic domain patterns.

PubMed

Su, Run; Seu, Keoki A; Parks, Daniel; Kan, Jimmy J; Fullerton, Eric E; Roy, Sujoy; Kevan, Stephen D

2011-12-16

Uniaxial systems often form labyrinthine domains that exhibit short-range order but are macroscopically isotropic and would not be expected to exhibit precise symmetries. However, their underlying frustration results in a multitude of metastable configurations of comparable energy, and driving such a system externally might lead to pattern formation. We find that soft x-ray speckle diffraction patterns of the labyrinthine domains in CoPd/IrMn heterostructures reveal a diverse array of hidden rotational symmetries about the magnetization axis, thereby suggesting an unusual form of emergent order in an otherwise disordered system. These symmetries depend on applied magnetic field, magnetization history, and scattering wave vector. Maps of rotational symmetry exhibit intriguing structures that can be controlled by manipulating the applied magnetic field in concert with the exchange bias condition. © 2011 American Physical Society

Isolation and Characterization of Human Mesenchymal Stem Cells From Facet Joints and Interspinous Ligaments.

PubMed

Kristjánsson, Baldur; Limthongkul, Worawat; Yingsakmongkol, Wicharn; Thantiworasit, Pattarawat; Jirathanathornnukul, Napaphat; Honsawek, Sittisak

2016-01-01

A descriptive in vitro study on isolation and differentiation of human mesenchymal stem cells (MSCs) derived from the facet joints and interspinous ligaments. To isolate cells from the facet joints and interspinous ligaments and investigate their surface marker profile and differentiation potentials. Lumbar spinal canal stenosis and ossification of the posterior longitudinal ligament are progressive conditions characterized by the hypertrophy and ossification of ligaments and joints within the spinal canal. MSCs are believed to play a role in the advancement of these diseases and the existence of MSCs has been demonstrated within the ligamentum flavum and posterior longitudinal ligament. The aim of this study was to investigate whether these cells could also be found within facet joints and interspinous ligaments. Samples were harvested from 10 patients undergoing spinal surgery. The MSCs from facet joints and interspinous ligaments were isolated using direct tissue explant technique. Cell surface antigen profilings were performed via flow cytometry. Their lineage differentiation potentials were analyzed. The facet joints and interspinous ligaments-derived MSCs have the tri-lineage potential to be differentiated into osteogenic, adipogenic, and chondrogenic cells under appropriate inductions. Flow cytometry analysis revealed both cell lines expressed MSCs markers. Both facet joints and interspinous ligaments-derived MSCs expressed marker genes for osteoblasts, adipocytes, and chondrocytes. The facet joints and interspinous ligaments may provide alternative sources of MSCs for tissue engineering applications. The facet joints and interspinous ligaments-derived MSCs are part of the microenvironment of the human ligaments of the spinal column and might play a crucial role in the development and progression of degenerative spine conditions.

Differentiating Knowledge, Differentiating (Occupational) Practice

ERIC Educational Resources Information Center

Hordern, Jim

2016-01-01

This paper extends arguments for differentiating knowledge into conceptualisations of occupational practice. It is argued that specialised forms of knowledge and practice require recognition and differentiation in ways that many contemporary approaches to practice theory deny. Drawing on Hager's interpretation of MacIntyre, it is suggested that…

Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

PubMed

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

2005-05-01

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

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: A case report of sustained hematologic response following an abbreviated exposure

PubMed Central

2010-01-01

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of ~50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide. PMID:20416051

Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.

PubMed

Quddus, Fahd; Clima, Jessica; Seedham, Helen; Sajjad, Ghulam; Galili, Naomi; Raza, Azra

2010-04-23

Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.

Role of the CD34+ 38- cells in posttransplant hematopoietic recovery.

PubMed

Hénon, P; Sovalat, H; Bourderont, D; Ojeda-Uribe, M; Arkam, Y; Wunder, E; Raidot, J P; Husseini, F; Audhuy, B

1998-01-01

Using three different statistical tests in parallel, we showed in a preliminary study that neither mononuclear cells, CD34+ 33+ or 33- cells, nor CD34+ 38+ cells significantly correlated with engraftment kinetics following autologous blood cell transplantation (ABCT). We additionally demonstrated here, in a series of patients suffering from malignant diseases, that the graft content in CD34+ 38- cells is individually a more sensitive indicator of the earliest, as well as the latest post-ABCT trilineage hematopoietic recovery than the colony-forming units-granulocyte-macrophage and even the total CD34+ cell content. This suggests that the CD34+ 38- cell population is itself subdivided into two more subsets, one being already lineage-committed and responsible for short-term engraftment, the other containing only very primitive hematopoietic cells responsible for sustained engraftment. Strong arguments favor the probability that these subsets correspond to HLA-DR+ and DR cells, respectively. We also defined an optimal threshold value of 0.05 x 10(6) CD34+ 38- cells/kg of the patient's body weight (b.w.) above which a rapid and sustained trilineage engraftment safely occurs. In fact, infusion of lower numbers of cells seems to have a more significant impact on long-term compared to short-term neutrophil recovery and on platelet kinetics engraftment. We additionally looked for the eventual influence on engraftment time of the type of disease, and of post-ABCT administration of hematopoietic growth factors (HGF). When the type of disease appeared to have no influence on the engraftment time, posttransplant HGF administration significantly reduced the time to trilineage engraftment in patients transplanted with < 0.05 x 10(6) CD34+ 38- cells, thus justifying it in case of reinfusion of low numbers of CD34+ 38- cells. On the other hand, the administration of HGF after infusion of more than 0.05 x 10(6) CD34+ 38- cells/kg b.w. did not hasten more, or only very little, the

Abnormal placental development and early embryonic lethality in EpCAM-null mice.

PubMed

Nagao, Keisuke; Zhu, Jianjian; Heneghan, Mallorie B; Hanson, Jeffrey C; Morasso, Maria I; Tessarollo, Lino; Mackem, Susan; Udey, Mark C

2009-12-31

EpCAM (CD326) is encoded by the tacstd1 gene and expressed by a variety of normal and malignant epithelial cells and some leukocytes. Results of previous in vitro experiments suggested that EpCAM is an intercellular adhesion molecule. EpCAM has been extensively studied as a potential tumor marker and immunotherapy target, and more recent studies suggest that EpCAM expression may be characteristic of cancer stem cells. To gain insights into EpCAM function in vivo, we generated EpCAM -/- mice utilizing an embryonic stem cell line with a tacstd1 allele that had been disrupted. Gene trapping resulted in a protein comprised of the N-terminus of EpCAM encoded by 2 exons of the tacstd1 gene fused in frame to betageo. EpCAM +/- mice were viable and fertile and exhibited no obvious abnormalities. Examination of EpCAM +/- embryos revealed that betageo was expressed in several epithelial structures including developing ears (otocysts), eyes, branchial arches, gut, apical ectodermal ridges, lungs, pancreas, hair follicles and others. All EpCAM -/- mice died in utero by E12.5, and were small, developmentally delayed, and displayed prominent placental abnormalities. In developing placentas, EpCAM was expressed throughout the labyrinthine layer and by spongiotrophoblasts as well. Placentas of EpCAM -/- embryos were compact, with thin labyrinthine layers lacking prominent vascularity. Parietal trophoblast giant cells were also dramatically reduced in EpCAM -/- placentas. EpCAM was required for differentiation or survival of parietal trophoblast giant cells, normal development of the placental labyrinth and establishment of a competent maternal-fetal circulation. The findings in EpCAM-reporter mice suggest involvement of this molecule in development of vital organs including the gut, kidneys, pancreas, lungs, eyes, and limbs.

Differential transimpedance amplifier circuit for correlated differential amplification

DOEpatents

Gresham, Christopher A [Albuquerque, NM; Denton, M Bonner [Tucson, AZ; Sperline, Roger P [Tucson, AZ

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.

Lecto- and epitypification of Morchella steppicola (Morchellaceae, Pezizales), a morphologically, phylogenetically, and biogeographically distinct member of the Esculenta Clade from central Eurasia

USDA-ARS?s Scientific Manuscript database

The steppe morel, Morchella steppicola, is one of the more iconic species of true morels (Morchellaceae, Pezizales) based on its: 1) distinctive cerebriform pileus with densely packed labyrinthine irregular ridges, 2) genealogically exclusive position as the earliest diverging species lineage within...

Periodontal regeneration using periodontal ligament stem cell-transferred amnion.

PubMed

Iwasaki, Kengo; Komaki, Motohiro; Yokoyama, Naoki; Tanaka, Yuichi; Taki, Atsuko; Honda, Izumi; Kimura, Yasuyuki; Takeda, Masaki; Akazawa, Keiko; Oda, Shigeru; Izumi, Yuichi; Morita, Ikuo

2014-02-01

Periodontal disease is characterized by the destruction of tooth supporting tissues. Regeneration of periodontal tissues using ex vivo expanded cells has been introduced and studied, although appropriate methodology has not yet been established. We developed a novel cell transplant method for periodontal regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic membrane (PDLSC-amnion). The aim of this study was to investigate the regenerative potential of PDLSC-amnion in a rat periodontal defect model. Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate treated with polyethylene glycol and photolithography. The properties of PDLSCs were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion was transplanted into surgically created periodontal defects in rat maxillary molars. Periodontal regeneration was evaluated by microcomputed tomography (micro-CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105, CD146, and STRO-1) and trilineage differentiation ability (i.e., into osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer of PDLSCs on the amniotic membrane and stability of the sheet even with movement and deformation caused by surgical instruments. We observed that the PDLSC-amnion enhanced periodontal tissue regeneration as determined by micro-CT and histology by 4 weeks after transplantation. These data suggest that PDLSC-amnion has therapeutic potential as a novel cell-based regenerative periodontal therapy.

Materials for Neural Differentiation, Trans-Differentiation, and Modeling of Neurological Disease.

PubMed

Gong, Lulu; Cao, Lining; Shen, Zhenmin; Shao, Li; Gao, Shaorong; Zhang, Chao; Lu, Jianfeng; Li, Weida

2018-04-01

Neuron regeneration from pluripotent stem cells (PSCs) differentiation or somatic cells trans-differentiation is a promising approach for cell replacement in neurodegenerative diseases and provides a powerful tool for investigating neural development, modeling neurological diseases, and uncovering the mechanisms that underlie diseases. Advancing the materials that are applied in neural differentiation and trans-differentiation promotes the safety, efficiency, and efficacy of neuron regeneration. In the neural differentiation process, matrix materials, either natural or synthetic, not only provide a structural and biochemical support for the monolayer or three-dimensional (3D) cultured cells but also assist in cell adhesion and cell-to-cell communication. They play important roles in directing the differentiation of PSCs into neural cells and modeling neurological diseases. For the trans-differentiation of neural cells, several materials have been used to make the conversion feasible for future therapy. Here, the most current applications of materials for neural differentiation for PSCs, neuronal trans-differentiation, and neurological disease modeling is summarized and discussed. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

As Patient Navigation Expands and Evolves, Nurses Assume Many Roles

Cancer.gov

It can be difficult to access care in our labyrinthine health care system. Oncology nurses are joining the ranks of patient navigators—a diverse group of people who help patients at all stages of cancer care, from screening and diagnosis to treatment and survivorship.

Characterization and Classification of Mesenchymal Stem Cells in Several Species Using Surface Markers for Cell Therapy Purposes.

PubMed

Ghaneialvar, Hori; Soltani, Leila; Rahmani, Hamid Reza; Lotfi, Abbas Sahebghadam; Soleimani, Masoud

2018-01-01

Mesenchymal stem cells are multipotent cells capable of replicating as undifferentiated cells, and have the potential of differentiating into mesenchymal tissue lineages such as osteocytes, adipocytes and chondrocytes. Such lineages can then be used in cell therapy. The aim of present study was to characterize bone marrow derived mesenchymal stem cells in four different species, including: sheep, goat, human and mouse. Human bone-marrow mesenchymal stem cells were purchased, those of sheep and goat were isolated from fetal bone marrow, and those of mouse were collected by washing bone cavity of femur and tibia with DMEM/F12. Using flow-cytometry, they were characterized by CD surface antigens. Furthermore, cells of third passage were examined for their osteogenic and adipogenic differentiation potential by oil red and alizarin red staining respectively. According to the results, CD markers studied in the four groups of mesenchymal stem cells showed a different expression. Goat and sheep expressed CD44 and CD166, and weakly expressed CD34, CD45, CD105 and CD90. Similarly, human and mouse mesenchymal cells expressed CD44, CD166, CD105 and CD90 whereas the expression of CD34 and CD45 was negative. In conclusion, although all mesenchymal stem cells display plastic adherence and tri-lineage differentiation, not all express the same panel of surface antigens described for human mesenchymal stem cells. Additional panel of CD markers are necessary to characterize regenerative potential and possible application of these stem cells in regenerative medicine and implantology.

High and Low Molecular Weight Hyaluronic Acid Differentially Regulate Human Fibrocyte Differentiation

PubMed Central

Maharjan, Anu S.; Pilling, Darrell; Gomer, Richard H.

2011-01-01

Background Following tissue injury, monocytes can enter the tissue and differentiate into fibroblast-like cells called fibrocytes, but little is known about what regulates this differentiation. Extracellular matrix contains high molecular weight hyaluronic acid (HMWHA; ∼2×106 Da). During injury, HMWHA breaks down to low molecular weight hyaluronic acid (LMWHA; ∼0.8–8×105 Da). Methods and Findings In this report, we show that HMWHA potentiates the differentiation of human monocytes into fibrocytes, while LMWHA inhibits fibrocyte differentiation. Digestion of HMWHA with hyaluronidase produces small hyaluronic acid fragments, and these fragments inhibit fibrocyte differentiation. Monocytes internalize HMWHA and LMWHA equally well, suggesting that the opposing effects on fibrocyte differentiation are not due to differential internalization of HMWHA or LMWHA. Adding HMWHA to PBMC does not appear to affect the levels of the hyaluronic acid receptor CD44, whereas adding LMWHA decreases CD44 levels. The addition of anti-CD44 antibodies potentiates fibrocyte differentiation, suggesting that CD44 mediates at least some of the effect of hyaluronic acid on fibrocyte differentiation. The fibrocyte differentiation-inhibiting factor serum amyloid P (SAP) inhibits HMWHA-induced fibrocyte differentiation and potentiates LMWHA-induced inhibition. Conversely, LMWHA inhibits the ability of HMWHA, interleukin-4 (IL-4), or interleukin-13 (IL-13) to promote fibrocyte differentiation. Conclusions We hypothesize that hyaluronic acid signals at least in part through CD44 to regulate fibrocyte differentiation, with a dominance hierarchy of SAP>LMWHA≥HMWHA>IL-4 or IL-13. PMID:22022512

Transsphenoidal and infralabyrinthine approach of the petrous apex cholesterol granuloma.

PubMed

Bruchhage, Karl-Ludwig; Wollenberg, Barbara; Leichtle, Anke

2017-07-01

Space-demanding or destructive changes in the petrous bone are often challenging differential diagnosis. Cholesterol granulomas of the petrous apex can clinically present in a combination of hearing loss, vertigo, tinnitus, chronic cephalgia, impairment of facial nerve function, neuralgic pain of the nervus trigeminus, or manifest diplopia by the nerve palsy of the nervus abducens. CT-morphologically cholesterol granulomas appear as soft-tissue density masses, which may display a discrete rim after intravenous administration of a contrast agent. The MRI, T1 as well as T2-weighted images show a strong signal in the area of the lesion. Depending on the individual anatomical conditions, the surgical access must be carefully chosen between transsphenoidal, transtemporal, infracochlear/-labyrinthine, or translabyrinthine. Here, we present the transsphenoidal and translabyrinthine access for the excision of cholesterol granulomas of the petrous apex. The different accesses are compared using a neuro-navigation-supported surgical technique with respect to its complications, drainage possibilities, outcomes, and recurrence of symptoms.

R-spondin3 is required for mouse placental development.

PubMed

Aoki, Motoko; Mieda, Michihiro; Ikeda, Toshio; Hamada, Yoshio; Nakamura, Harukazu; Okamoto, Hitoshi

2007-01-01

Mouse R-spondin3 (Rspo3) is a member of the R-spondin protein family, which is characterized by furin-like cysteine-rich domains and a thrombospondin type 1 repeat. Rspo3 has been proposed to function as a secretory molecule that promotes the Wnt/beta-catenin signaling pathway. We generated mice bearing a mutant Rspo3 allele in which a lacZ-coding region replaced the coding region of the first exon. The homozygous mutant mice died at about embryonic day 10, due to impaired formation of the labyrinthine layer of the placenta. Rspo3 was expressed in the allantoic component of the labyrinth. In the homozygous mutant placentas, fetal blood vessels did not penetrate into the chorion, and expression of Gcm1, encoding the transcription factor glial cells missing-1 (Gcm1), was dramatically reduced in the chorionic trophoblast cells. These findings suggest a critical role for Rspo3 in the interaction between chorion and allantois in labyrinthine development.

Differentiation therapy revisited.

PubMed

de Thé, Hugues

2018-02-01

The concept of differentiation therapy emerged from the fact that hormones or cytokines may promote differentiation ex vivo, thereby irreversibly changing the phenotype of cancer cells. Its hallmark success has been the treatment of acute promyelocytic leukaemia (APL), a condition that is now highly curable by the combination of retinoic acid (RA) and arsenic. Recently, drugs that trigger differentiation in a variety of primary tumour cells have been identified, suggesting that they are clinically useful. This Opinion article analyses the basis for the clinical successes of RA or arsenic in APL by assessing the respective roles of terminal maturation and loss of self-renewal. By reviewing other successful examples of drug-induced tumour cell differentiation, novel approaches to transform differentiating drugs into more efficient therapies are proposed.

Nonlinear differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

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 ismore » 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.« less

Wharton's Jelly Derived Mesenchymal Stem Cells: Comparing Human and Horse.

PubMed

Merlo, Barbara; Teti, Gabriella; Mazzotti, Eleonora; Ingrà, Laura; Salvatore, Viviana; Buzzi, Marina; Cerqueni, Giorgia; Dicarlo, Manuela; Lanci, Aliai; Castagnetti, Carolina; Iacono, Eleonora

2018-08-01

Wharton's jelly (WJ) is an important source of mesenchymal stem cells (MSCs) both in human and other animals. The aim of this study was to compare human and equine WJMSCs. Human and equine WJMSCs were isolated and cultured using the same protocols and culture media. Cells were characterized by analysing morphology, growth rate, migration and adhesion capability, immunophenotype, differentiation potential and ultrastructure. Results showed that human and equine WJMSCs have similar ultrastructural details connected with intense synthetic and metabolic activity, but differ in growth, migration, adhesion capability and differentiation potential. In fact, at the scratch assay and transwell migration assay, the migration ability of human WJMSCs was higher (P < 0.05) than that of equine cells, while the volume of spheroids obtained after 48 h of culture in hanging drop was larger than the volume of equine ones (P < 0.05), demonstrating a lower cell adhesion ability. This can also revealed in the lower doubling time of equine cells (3.5 ± 2.4 days) as compared to human (6.5 ± 4.3 days) (P < 0.05), and subsequently in the higher number of cell doubling after 44 days of culture observed for the equine (20.3 ± 1.7) as compared to human cells (8.7 ± 2.4) (P < 0.05), and to the higher (P < 0.05) ability to form fibroblast colonies at P3. Even if in both species tri-lineage differentiation was achieved, equine cells showed an higher chondrogenic and osteogenic differentiation ability (P < 0.05). Our findings indicate that, although the ultrastructure demonstrated a staminal phenotype in human and equine WJMSCs, they showed different properties reflecting the different sources of MSCs.

Decision Making Perspectives of Young Children (K-5).

ERIC Educational Resources Information Center

Rogers, Linda J.; McDonald, Linda L.

1999-01-01

Applies Blumer's theory of symbolic interactionism to explore how normal children make meaning of their decision making world, both of their own acts and the labyrinthine world adults structure for them. Schema/narratives on friendship, sports, adults, and school reveal knowledge making strategies defined by immediate experiences and a capacity to…

Differentiated Staffing.

ERIC Educational Resources Information Center

Nassau County Board of Cooperative Educational Services, Westbury, NY.

This is a compilation of articles examining many aspects of differentiated staffing and creating a basic document for all school districts. The articles are grouped into seven sections: 1) "Why Change?"; 2) "A Consideration of Staffing Problems"; 3) "Critics and Crusaders: An Analysis of Differentiated Staffing" (subsections on concept and…

Fast isolation and expansion of multipotent cells from adipose tissue based on chitosan-selected primary culture.

PubMed

Huang, Guo-Shiang; Tseng, Ting-Chen; Dai, Niann-Tzyy; Fu, Keng-Yen; Dai, Lien-Guo; Hsu, Shan-Hui

2015-10-01

Adipose-derived adult stem cells (ASCs) have gained much attention because of their multipotency and easy access. Here we describe a novel chitosan-based selection (CS) system instead of the conventional plastic adherence (PA) to obtain the primary ASCs. The minimal amount of adipose tissue for consistent isolation of ASCs is reduced from 10 mL to 5 mL. The selection is based on the specific interaction between cells and chitosan materials, which separate ASCs by forming spheroids during primary culture. The primary culture period was reduced from 4 days to one day and more ASCs (ten-fold expansion) were achieved in a week. The average duration for obtaining 1 × 10(7) cells takes about seven days from 5 mL of adipose tissue, compared to 14 days using the conventional PA method from 10 mL of adipose tissue. The replicative senescence of CS-ASCs is not evident until the fifteenth passage (vs. eighth for the PA-ASCs). The obtained ASCs (CS-ASCs) have less doubling time for the same passage of cells and show greater stemness than those obtained from the conventional PA method (PA-ASCs). Moreover, CS-ASCs undergo trilineage differentiation more effectively than PA-ASCs. The greater differentiation potential of CS-ASCs may be associated with the enrichment and maintenance of CD271 positive cells by chitosan selection of primary culture. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mechanical fibrinogen-depletion supports heparin-free mesenchymal stem cell propagation in human platelet lysate.

PubMed

Laner-Plamberger, Sandra; Lener, Thomas; Schmid, Doris; Streif, Doris A; Salzer, Tina; Öller, Michaela; Hauser-Kronberger, Cornelia; Fischer, Thorsten; Jacobs, Volker R; Schallmoser, Katharina; Gimona, Mario; Rohde, Eva

2015-11-10

Pooled human platelet lysate (pHPL) is an efficient alternative to xenogenic supplements for ex vivo expansion of mesenchymal stem cells (MSCs) in clinical studies. Currently, porcine heparin is used in pHPL-supplemented medium to prevent clotting due to plasmatic coagulation factors. We therefore searched for an efficient and reproducible medium preparation method that avoids clot formation while omitting animal-derived heparin. We established a protocol to deplete fibrinogen by clotting of pHPL in medium, subsequent mechanical hydrogel disruption and removal of the fibrin pellet. After primary culture, bone-marrow and umbilical cord derived MSCs were tested for surface markers by flow cytometry and for trilineage differentiation capacity. Proliferation and clonogenicity were analyzed for three passages. The proposed clotting procedure reduced fibrinogen more than 1000-fold, while a volume recovery of 99.5 % was obtained. All MSC types were propagated in standard and fibrinogen-depleted medium. Flow cytometric phenotype profiles and adipogenic, osteogenic and chondrogenic differentiation potential in vitro were independent of MSC-source or medium type. Enhanced proliferation of MSCs was observed in the absence of fibrinogen but presence of heparin compared to standard medium. Interestingly, this proliferative response to heparin was not detected after an initial contact with fibrinogen during the isolation procedure. Here, we present an efficient, reproducible and economical method in compliance to good manufacturing practice for the preparation of MSC media avoiding xenogenic components and suitable for clinical studies.

Periodontal Regeneration Using Periodontal Ligament Stem Cell-Transferred Amnion

PubMed Central

Iwasaki, Kengo; Yokoyama, Naoki; Tanaka, Yuichi; Taki, Atsuko; Honda, Izumi; Kimura, Yasuyuki; Takeda, Masaki; Akazawa, Keiko; Oda, Shigeru; Izumi, Yuichi; Morita, Ikuo

2014-01-01

Periodontal disease is characterized by the destruction of tooth supporting tissues. Regeneration of periodontal tissues using ex vivo expanded cells has been introduced and studied, although appropriate methodology has not yet been established. We developed a novel cell transplant method for periodontal regeneration using periodontal ligament stem cell (PDLSC)-transferred amniotic membrane (PDLSC-amnion). The aim of this study was to investigate the regenerative potential of PDLSC-amnion in a rat periodontal defect model. Cultured PDLSCs were transferred onto amniotic membranes using a glass substrate treated with polyethylene glycol and photolithography. The properties of PDLSCs were investigated by flow cytometry and in vitro differentiation. PDLSC-amnion was transplanted into surgically created periodontal defects in rat maxillary molars. Periodontal regeneration was evaluated by microcomputed tomography (micro-CT) and histological analysis. PDLSCs showed mesenchymal stem cell-like characteristics such as cell surface marker expression (CD90, CD44, CD73, CD105, CD146, and STRO-1) and trilineage differentiation ability (i.e., into osteoblasts, adipocytes, and chondrocytes). PDLSC-amnion exhibited a single layer of PDLSCs on the amniotic membrane and stability of the sheet even with movement and deformation caused by surgical instruments. We observed that the PDLSC-amnion enhanced periodontal tissue regeneration as determined by micro-CT and histology by 4 weeks after transplantation. These data suggest that PDLSC-amnion has therapeutic potential as a novel cell-based regenerative periodontal therapy. PMID:24032400

Characterization of Canine Adipose-Derived Mesenchymal Stromal/Stem Cells in Serum-Free Medium.

PubMed

Liu, Zhuoming; Screven, Rudell; Boxer, Lynne; Myers, Michael J; Devireddy, Lax R

2018-06-20

In this article, we report on the development of a defined serum-free medium capable of supporting the culture expansion of mesenchymal stromal/stem cells (MSCs) from canine adipose tissue (canine Ad-MSCs). The potential benefits of serum-free media can only be utilized if cells cultured in serum-free media maintain the same functional characteristics as cells cultured in serum-containing media. Therefore, we analyze the characteristics of canine Ad-MSCs cultured in this serum-free medium or in serum-containing medium through evaluation of growth kinetics, clonogenic capacity, senescence, and differentiation capacity. Both, serum-containing medium and our serum-free medium, supported efficient growth and colony formation of canine Ad-MSCs. In addition, canine Ad-MSCs cultured in both media demonstrated similar viability after freeze/thaw, similar cell surface marker expression, and were capable of trilineage differentiation. While canine Ad-MSCs cultured in both media were generally similar, under the conditions of our study, canine Ad-MSCs cultured in serum-free medium demonstrated a shorter lag phase and higher colony-forming capacity, accelerated population doubling, maintained multipotentiality at higher passage numbers, and underwent senescence at higher passage numbers compared to canine Ad-MSCs cultured in conventional serum-containing medium. These results suggest that canine Ad-MSCs cultured in serum-free medium retain the basic characteristics associated with canine Ad-MSCs cultured in serum-containing medium, although some differences in growth kinetics were observed.

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…

Primitive Reflexes and Attention-Deficit/Hyperactivity Disorder: Developmental Origins of Classroom Dysfunction

ERIC Educational Resources Information Center

Taylor, Myra; Houghton, Stephen; Chapman, Elaine

2004-01-01

The present research studied the symptomatologic overlap of AD/HD behaviours and retention of four primitive reflexes (Moro, Tonic Labyrinthine Reflex [TLR], Asymmetrical Tonic Neck Reflex [ATNR], Symmetrical Tonic Neck Reflex [STNR]) in 109 boys aged 7-10 years. Of these, 54 were diagnosed with AD/HD, 34 manifested sub-syndromal coordination,…

Donor-Matched Comparison of Chondrogenic Potential of Equine Bone Marrow- and Synovial Fluid-Derived Mesenchymal Stem Cells: Implications for Cartilage Tissue Regeneration

PubMed Central

Zayed, Mohammed; Caniglia, Christopher; Misk, Nabil; Dhar, Madhu S.

2017-01-01

Mesenchymal stem cells (MSCs) have been demonstrated to be useful for cartilage tissue regeneration. Bone marrow (BM) and synovial fluid (SF) are promising sources for MSCs to be used in cartilage regeneration. In order to improve the clinical outcomes, it is recommended that prior to clinical use, the cellular properties and, specifically, their chondrogenic potential must be investigated. The purpose of this study is to compare and better understand the in vitro chondrogenic potential of equine bone marrow-derived mesenchymal stem cells (BMMSCs) and synovial fluid-derived mesenchymal stem cells (SFMSCs) populated from the same equine donor. BM- and SF-derived MSCs cultures were generated from five equine donors, and the MSCs were evaluated in vitro for their morphology, proliferation, trilineage differentiation, and immunophenotyping. Differences in their chondrogenic potentials were further evaluated quantitatively using glycosaminoglycan (GAG) content and via immunofluorescence of chondrogenic differentiation protein markers, SRY-type HMG box9, Aggrecan, and collagen II. The BMMSCs and SFMSCs were similar in cellular morphology, viability, and immunophenotype, but, varied in their chondrogenic potential, and expression of the key chondrogenic proteins. The SFMSCs exhibited a significant increase in GAG content compared to the BMMSCs (P < 0.0001) in three donors, suggesting increased levels of chondrogenesis. The expression of the key chondrogenic proteins correlated positively with the GAG content, suggesting that the differentiation process is dependent on the expression of the target proteins in these three donors. Our findings suggest that even though SFMSCs were hypothesized to be more chondrogenic relative to BMMSCs, there was considerable donor-to-donor variation in the primary cultures of MSCs which can significantly affect their downstream application. PMID:28149840

Mangiferin positively regulates osteoblast differentiation and suppresses osteoclast differentiation

PubMed Central

Sekiguchi, Yuusuke; Mano, Hiroshi; Nakatani, Sachie; Shimizu, Jun; Kataoka, Aya; Ogura, Kana; Kimira, Yoshifumi; Ebata, Midori; Wada, Masahiro

2017-01-01

Mangiferin is a polyphenolic compound present in Salacia reticulata. It has been reported to reduce bone destruction and inhibit osteoclastic differentiation. This study aimed to determine whether mangiferin directly affects osteoblast and osteoclast proliferation and differentiation, and gene expression in MC3T3-E1 osteoblastic cells and osteoclast-like cells derived from primary mouse bone marrow macrophage cells. Mangiferin induced significantly greater WST-1 activity, indicating increased cell proliferation. Mangiferin induced significantly increased alkaline phosphatase staining, indicating greater cell differentiation. Reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mangiferin significantly increased the mRNA level of runt-related transcription factor 2 (RunX2), but did not affect RunX1 mRNA expression. Mangiferin significantly reduced the formation of tartrate-resistant acid phosphatase-positive multinuclear cells. RT-PCR demonstrated that mangiferin significantly increased the mRNA level of estrogen receptor β (ERβ), but did not affect the expression of other osteoclast-associated genes. Mangiferin may inhibit osteoclastic bone resorption by suppressing differentiation of osteoclasts and promoting expression of ERβ mRNA in mouse bone marrow macrophage cells. It also has potential to promote osteoblastic bone formation by promoting cell proliferation and inducing cell differentiation in preosteoblast MC3T3-E1 cells via RunX2. Mangiferin may therefore be useful in improving bone disease outcomes. PMID:28627701

Mangiferin positively regulates osteoblast differentiation and suppresses osteoclast differentiation.

PubMed

Sekiguchi, Yuusuke; Mano, Hiroshi; Nakatani, Sachie; Shimizu, Jun; Kataoka, Aya; Ogura, Kana; Kimira, Yoshifumi; Ebata, Midori; Wada, Masahiro

2017-08-01

Mangiferin is a polyphenolic compound present in Salacia reticulata. It has been reported to reduce bone destruction and inhibit osteoclastic differentiation. This study aimed to determine whether mangiferin directly affects osteoblast and osteoclast proliferation and differentiation, and gene expression in MC3T3‑E1 osteoblastic cells and osteoclast‑like cells derived from primary mouse bone marrow macrophage cells. Mangiferin induced significantly greater WST‑1 activity, indicating increased cell proliferation. Mangiferin induced significantly increased alkaline phosphatase staining, indicating greater cell differentiation. Reverse transcription‑polymerase chain reaction (RT‑PCR) demonstrated that mangiferin significantly increased the mRNA level of runt‑related transcription factor 2 (RunX2), but did not affect RunX1 mRNA expression. Mangiferin significantly reduced the formation of tartrate‑resistant acid phosphatase‑positive multinuclear cells. RT‑PCR demonstrated that mangiferin significantly increased the mRNA level of estrogen receptor β (ERβ), but did not affect the expression of other osteoclast‑associated genes. Mangiferin may inhibit osteoclastic bone resorption by suppressing differentiation of osteoclasts and promoting expression of ERβ mRNA in mouse bone marrow macrophage cells. It also has potential to promote osteoblastic bone formation by promoting cell proliferation and inducing cell differentiation in preosteoblast MC3T3‑E1 cells via RunX2. Mangiferin may therefore be useful in improving bone disease outcomes.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Watanabe, Tomonobu M.; World Premier Initiative, iFREC, Osaka University, Osaka 565-0871; Higuchi, Sayaka

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

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.

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.

Poorly Differentiated Thyroid Carcinoma.

PubMed

Setia, Namrata; Barletta, Justine A

2014-12-01

Poorly differentiated thyroid carcinoma (PDTC) has been recognized for the past 30 years as an entity showing intermediate differentiation and clinical behavior between well-differentiated thyroid carcinomas (ie, papillary thyroid carcinoma and follicular thyroid carcinoma) and anaplastic thyroid carcinoma; however, there has been considerable controversy around the definition of PDTC. In this review, the evolution in the definition of PDTC, current diagnostic criteria, differential diagnoses, potentially helpful immunohistochemical studies, and molecular alterations are discussed with the aim of highlighting where the diagnosis of PDTC currently stands. Published by Elsevier Inc.

Auto-Zero Differential Amplifier

NASA Technical Reports Server (NTRS)

Quilligan, Gerard T. (Inventor); Aslam, Shahid (Inventor)

2017-01-01

An autozero amplifier may include a window comparator network to monitor an output offset of a differential amplifier. The autozero amplifier may also include an integrator to receive a signal from a latched window comparator network, and send an adjustment signal back to the differential amplifier to reduce an offset of the differential amplifier.

Teacher Teams Help Schools Turn Around

ERIC Educational Resources Information Center

Sawchuk, Stephen

2011-01-01

It's hard to imagine two schools superficially more different from each other than Blackstone Elementary, with its labyrinthine 1970s layout, and Orchard Gardens K-8 School, which opened in 2003, with its modern skylights and cheery primary-color accents. But they were similar in the way that matters most in young lives: Both Boston schools were…

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.

Mirna biogenesis pathway is differentially regulated during adipose derived stromal/stem cell differentiation.

PubMed

Martin, E C; Qureshi, A T; Llamas, C B; Burow, M E; King, A G; Lee, O C; Dasa, V; Freitas, M A; Forsberg, J A; Elster, E A; Davis, T A; Gimble, J M

2018-02-07

Stromal/stem cell differentiation is controlled by a vast array of regulatory mechanisms. Included within these are methods of mRNA gene regulation that occur at the level of epigenetic, transcriptional, and/or posttranscriptional modifications. Current studies that evaluate the posttranscriptional regulation of mRNA demonstrate microRNAs (miRNAs) as key mediators of stem cell differentiation through the inhibition of mRNA translation. miRNA expression is enhanced during both adipogenic and osteogenic differentiation; however, the mechanism by which miRNA expression is altered during stem cell differentiation is less understood. Here we demonstrate for the first time that adipose-derived stromal/stem cells (ASCs) induced to an adipogenic or osteogenic lineage have differences in strand preference (-3p and -5p) for miRNAs originating from the same primary transcript. Furthermore, evaluation of miRNA expression in ASCs demonstrates alterations in both miRNA strand preference and 5'seed site heterogeneity. Additionally, we show that during stem cell differentiation there are alterations in expression of genes associated with the miRNA biogenesis pathway. Quantitative RT-PCR demonstrated changes in the Argonautes (AGO1-4), Drosha, and Dicer at intervals of ASC adipogenic and osteogenic differentiation compared to untreated ASCs. Specifically, we demonstrated altered expression of the AGOs occurring during both adipogenesis and osteogenesis, with osteogenesis increasing AGO1-4 expression and adipogenesis decreasing AGO1 gene and protein expression. These data demonstrate changes to components of the miRNA biogenesis pathway during stromal/stem cell differentiation. Identifying regulatory mechanisms for miRNA processing during ASC differentiation may lead to novel mechanisms for the manipulation of lineage differentiation of the ASC through the global regulation of miRNA as opposed to singular regulatory mechanisms.

DCGL v2.0: an R package for unveiling differential regulation from differential co-expression.

PubMed

Yang, Jing; Yu, Hui; Liu, Bao-Hong; Zhao, Zhongming; Liu, Lei; Ma, Liang-Xiao; Li, Yi-Xue; Li, Yuan-Yuan

2013-01-01

Differential co-expression analysis (DCEA) has emerged in recent years as a novel, systematic investigation into gene expression data. While most DCEA studies or tools focus on the co-expression relationships among genes, some are developing a potentially more promising research domain, differential regulation analysis (DRA). In our previously proposed R package DCGL v1.0, we provided functions to facilitate basic differential co-expression analyses; however, the output from DCGL v1.0 could not be translated into differential regulation mechanisms in a straightforward manner. To advance from DCEA to DRA, we upgraded the DCGL package from v1.0 to v2.0. A new module named "Differential Regulation Analysis" (DRA) was designed, which consists of three major functions: DRsort, DRplot, and DRrank. DRsort selects differentially regulated genes (DRGs) and differentially regulated links (DRLs) according to the transcription factor (TF)-to-target information. DRrank prioritizes the TFs in terms of their potential relevance to the phenotype of interest. DRplot graphically visualizes differentially co-expressed links (DCLs) and/or TF-to-target links in a network context. In addition to these new modules, we streamlined the codes from v1.0. The evaluation results proved that our differential regulation analysis is able to capture the regulators relevant to the biological subject. With ample functions to facilitate differential regulation analysis, DCGL v2.0 was upgraded from a DCEA tool to a DRA tool, which may unveil the underlying differential regulation from the observed differential co-expression. DCGL v2.0 can be applied to a wide range of gene expression data in order to systematically identify novel regulators that have not yet been documented as critical. DCGL v2.0 package is available at http://cran.r-project.org/web/packages/DCGL/index.html or at our project home page http://lifecenter.sgst.cn/main/en/dcgl.jsp.

Multi-output differential technologies

NASA Astrophysics Data System (ADS)

Bidare, Srinivas R.

1997-01-01

A differential is a very old and proven mechanical device that allows a single input to be split into two outputs having equal torque irrespective of the output speeds. A standard differential is capable of providing only two outputs from a single input. A recently patented multi-output differential technology known as `Plural-Output Differential' allows a single input to be split into many outputs. This new technology is the outcome of a systematic study of complex gear trains (Bidare 1992). The unique feature of a differential (equal torque at different speeds) can be applied to simplify the construction and operation of many complex mechanical devices that require equal torque's or forces at multiple outputs. It is now possible to design a mechanical hand with three or more fingers with equal torque. Since these finger are powered via a differential they are `mechanically intelligent'. A prototype device is operational and has been used to demonstrate the utility and flexibility of the design. In this paper we shall review two devices that utilize the new technology resulting in increased performance, robustness with reduced complexity and cost.

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.

Differential Pricing of Undergraduate Education.

ERIC Educational Resources Information Center

Yanikoski, Richard A.; Wilson, Richard F.

1984-01-01

The concept of differential pricing and its current application in undergraduate education are examined, particularly differentiating tuition by program at the upper-division level. Differential pricing is proposed as a policy that can benefit both students and institutions. (Author/MLW)

A novel protein expression signature differentiates benign lipomas from well-differentiated liposarcomas.

PubMed

Mather, Quang; Priego, Jonathon; Ward, Kristi; Kundan, Verma; Tran, Dat; Dwivedi, Alok; Bryan, Brad A

2017-09-01

Benign lipomas and well-differentiated liposarcomas share many histological and molecular features. Due to their similarities, patients with these lipomatous tumors are misdiagnosed up to 40% of the time following radiological detection, up to 17% of the time following histological examination, and in as many as 15% of cases following fluorescent in situ hybridization for chromosomal anomalies. Incorrect classification of these two tumor types leads to increased costs to the patient and delayed accurate diagnoses. In this study, we used genomics analysis to identify several genes whose mRNA expression patterns were significantly altered between lipomas and well-differentiated liposarcomas. We confirmed our findings at the protein level using a panel of 30 human lipomatous tumors, revealing that C4BPB, class II, major histocompatibility complex, CIITA, EPHB2, HOXB7, GLS2, RBBP5, and regulator of RGS2 protein levels were increased in well-differentiated liposarcomas compared to lipomas. We developed a multi-protein model of these markers to increase discriminatory ability, finding the combined expression model with CIITA and RGS2 provided a high ability (AUC=0.93) to differentiate between lipomas and well-differentiated liposarcomas with sensitivity at 83.3% and specificity at 90.9%.

PLACENTA OF THE INDIAN ELEPHANT, ELEPHAS INDICUS.

PubMed

COOPER, R A; CONNELL, R S; WELLINGS, S R

1964-10-16

The placenta of the Indian elephant is incompletely annular and zonary macroscopically and occupies the equator of an ovoid chorioallantoic sac. The amnion is fused with the chorion over the zone. Microscopically, the placenta is labyrinthine and endotheliochorial with a rudimentary marginal hematoma. Both macroscopically and microscopically it resembles the placentas of thecarnivores, particularly the racoon, the cat, and the dog.

Aspirin Enhances Osteogenic Potential of Periodontal Ligament Stem Cells (PDLSCs) and Modulates the Expression Profile of Growth Factor-Associated Genes in PDLSCs.

PubMed

Abd Rahman, Fazliny; Mohd Ali, Johari; Abdullah, Mariam; Abu Kasim, Noor Hayaty; Musa, Sabri

2016-07-01

This study investigates the effects of aspirin (ASA) on the proliferative capacity, osteogenic potential, and expression of growth factor-associated genes in periodontal ligament stem cells (PDLSCs). Mesenchymal stem cells (MSCs) from PDL tissue were isolated from human premolars (n = 3). The MSCs' identity was confirmed by immunophenotyping and trilineage differentiation assays. Cell proliferation activity was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Polymerase chain reaction array was used to profile the expression of 84 growth factor-associated genes. Pathway analysis was used to identify the biologic functions and canonic pathways activated by ASA treatment. The osteogenic potential was evaluated through mineralization assay. ASA at 1,000 μM enhances osteogenic potential of PDLSCs. Using a fold change (FC) of 2.0 as a threshold value, the gene expression analyses indicated that 19 genes were differentially expressed, which includes 12 upregulated and seven downregulated genes. Fibroblast growth factor 9 (FGF9), vascular endothelial growth factor A (VEGFA), interleukin-2, bone morphogenetic protein-10, VEGFC, and 2 (FGF2) were markedly upregulated (FC range, 6 to 15), whereas pleotropin, FGF5, brain-derived neurotrophic factor, and Dickkopf WNT signaling pathway inhibitor 1 were markedly downregulated (FC 32). Of the 84 growth factor-associated genes screened, 35 showed high cycle threshold values (≥35). ASA modulates the expression of growth factor-associated genes and enhances osteogenic potential in PDLSCs. ASA upregulated the expression of genes that could activate biologic functions and canonic pathways related to cell proliferation, human embryonic stem cell pluripotency, tissue regeneration, and differentiation. These findings suggest that ASA enhances PDLSC function and may be useful in regenerative dentistry applications, particularly in the areas of periodontal health and regeneration.

Amniotic Fluid Cells Show Higher Pluripotency-Related Gene Expression Than Allantoic Fluid Cells.

PubMed

Kehl, Debora; Generali, Melanie; Görtz, Sabrina; Geering, Diego; Slamecka, Jaroslav; Hoerstrup, Simon P; Bleul, Ulrich; Weber, Benedikt

2017-10-01

Amniotic fluid represents an abundant source of multipotent stem cells, referred as broadly multipotent given their differentiation potential and expression of pluripotency-related genes. However, the origin of this broadly multipotent cellular fraction is not fully understood. Several sources have been proposed so far, including embryonic and extraembryonic tissues. In this regard, the ovine developmental model uniquely allows for direct comparison of fetal fluid-derived cells from two separate fetal fluid cavities, the allantois and the amnion, over the entire duration of gestation. As allantoic fluid mainly collects fetal urine, cells originating from the efferent urinary tract can directly be compared with cells deriving from the extraembryonic amniotic tissues and the fetus. This study shows isolation of cells from the amniotic [ovine amniotic fluid cells (oAFCs)] and allantoic fluid [ovine allantoic fluid cells (oALCs)] in a strictly paired fashion with oAFCs and oALCs derived from the same fetus. Both cell types showed cellular phenotypes comparable to standard mesenchymal stem cells (MSCs), with trilineage differentiation potential, and expression of common ovine MSC markers. However, the expression of MSC markers per single cell was higher in oAFCs as measured by flow cytometry. oAFCs exhibited higher proliferative capacities and showed significantly higher expression of pluripotency-related genes OCT4, STAT3, NANOG, and REX1 by quantitative real-time polymerase chain reaction compared with paired oALCs. No significant decrease of pluripotency-related gene expression was noted over gestation, implying that cells with high differentiation potential may be isolated at the end of pregnancy. In conclusion, this study suggests that cells with highest stem cell characteristics may originate from the fetus itself or the amniotic fetal adnexa rather than from the efferent urinary tract or the allantoic fetal adnexa.

Two Pore Channel 2 Differentially Modulates Neural Differentiation of Mouse Embryonic Stem Cells

PubMed Central

Zhang, Zhe-Hao; Lu, Ying-Ying; Yue, Jianbo

2013-01-01

Nicotinic acid adenine dinucleotide phosphate (NAADP) is an endogenous Ca2+ mobilizing nucleotide presented in various species. NAADP mobilizes Ca2+ from acidic organelles through two pore channel 2 (TPC2) in many cell types and it has been previously shown that NAADP can potently induce neuronal differentiation in PC12 cells. Here we examined the role of TPC2 signaling in the neural differentiation of mouse embryonic stem (ES) cells. We found that the expression of TPC2 was markedly decreased during the initial ES cell entry into neural progenitors, and the levels of TPC2 gradually rebounded during the late stages of neurogenesis. Correspondingly, TPC2 knockdown accelerated mouse ES cell differentiation into neural progenitors but inhibited these neural progenitors from committing to neurons. Overexpression of TPC2, on the other hand, inhibited mouse ES cell from entering the early neural lineage. Interestingly, TPC2 knockdown had no effect on the differentiation of astrocytes and oligodendrocytes of mouse ES cells. Taken together, our data indicate that TPC2 signaling plays a temporal and differential role in modulating the neural lineage entry of mouse ES cells, in that TPC2 signaling inhibits ES cell entry to early neural progenitors, but is required for late neuronal differentiation. PMID:23776607

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.

Rapid isolation of bone marrow mesenchymal stromal cells using integrated centrifuge-based technology.

PubMed

Meppelink, Amanda M; Wang, Xing-Hua; Bradica, Gino; Barron, Kathryn; Hiltz, Kathleen; Liu, Xiang-Hong; Goldman, Scott M; Vacanti, Joseph P; Keating, Armand; Hoganson, David M

2016-06-01

The use of bone marrow-derived mesenchymal stromal cells (MSCs) in cell-based therapies is currently being developed for a number of diseases. Thus far, the clinical results have been inconclusive and variable, in part because of the variety of cell isolation procedures and culture conditions used in each study. A new isolation technique that streamlines the method of concentration and demands less time and attention could provide clinical and economic advantages compared with current methodologies. In this study, we evaluated the concentrating capability of an integrated centrifuge-based technology compared with standard Ficoll isolation. MSCs were concentrated from bone marrow aspirate using the new device and the Ficoll method. The isolation capabilities of the device and the growth characteristics, secretome production, and differentiation capacity of the derived cells were determined. The new MSC isolation device concentrated the bone marrow in 90 seconds and resulted in a mononuclear cell yield 10-fold higher and with a twofold increase in cell retention compared with Ficoll. The cells isolated using the device were shown to exhibit similar morphology and functional activity as assessed by growth curves and secretome production compared to the Ficoll-isolated cells. The surface marker and trilineage differentiation profile of the device-isolated cells was consistent with the known profile of MSCs. The faster time to isolation and greater cell yield of the integrated centrifuge-based technology may make this an improved approach for MSC isolation from bone marrow aspirates. Copyright © 2016 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

t(1;3)(p36;p21): presentation of a patient with MDS/AML (M2) and review of the literature.

PubMed

Güven, Gülgün S; Tarkan Argüden, Yelda; Öngören, Şeniz; Deviren, Ayhan; Aydın, Yıldız; Hacıhanefioglu, Seniha

2006-06-05

t(1;3)(p36;p21) is a recurrent reciprocal translocation found in a subset of myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML) characterized by trilineage dysplasia, especially dysmegakaryopoiesis and poor prognosis. In the literature, some authors have suggested that this recurrent translocation is closely associated with prior chemotherapy including alkylating agents in various hematologic malignancies. We identified a recurring translocation, t(1;3)(p36;p21), in our patient with MDS/AML(M2), although she had not been given any kind of treatment previously.

Trematode reproduction in the molluscan host: an ultrastructural study of the germinal mass in the rediae of Himasthla elongata (Mehlis, 1831) (Digenea: Echinostomatidae).

PubMed

Podvyaznaya, Irina M; Galaktionov, Kirill V

2014-03-01

The germinal mass in Himasthla elongata rediae was studied in detail using transmission electron microscopy. It was shown to be a specialized reproductive organ consisting of germinal cells at various maturation stages, supporting cells and stem cells. The germinal mass also contains early cercarial embryos emerging as a result of cleavage division of mature germinal cells. The stem cells that give rise to germinal cells have heterochromatin-rich nuclei with distinct nucleoli and scarce cytoplasm containing mainly free ribosomes and few mitochondria. The differentiating germinal cells undergo a growth, which is accompanied by an emergence of annulate lamellae and the nuage in their cytoplasm, a noticeable development of RER and Golgi apparatus and an increase in the number of mitochondria. The mitochondria form a large group at one of the cell poles. During differentiation, the nucleus and nucleolus of the germinal cell enlarge while the chromatin becomes gradually less condensed. The supporting tissue of the germinal mass is made up of cells connected by septate junctions. These supporting cells are distinctly different in cellular shape and nuclear ultrastructure. Their outgrowths form a tight meshwork housing stem cells, germinal cells and early cercarial embryos. The cytoplasm of the supporting cells in the mesh area is separated into fine parallel layers by labyrinthine narrow cavities communicating with the intercellular space. The supporting tissue contains differentiating and degenerating cells which indicates its renewal. The results of this ultrastructural study lend support to the hypothesis that the germinal cells of digeneans are germ line cells.

Differentiable McCormick relaxations

DOE PAGES

Khan, Kamil A.; Watson, Harry A. J.; Barton, Paul I.

2016-05-27

McCormick's classical relaxation technique constructs closed-form convex and concave relaxations of compositions of simple intrinsic functions. These relaxations have several properties which make them useful for lower bounding problems in global optimization: they can be evaluated automatically, accurately, and computationally inexpensively, and they converge rapidly to the relaxed function as the underlying domain is reduced in size. They may also be adapted to yield relaxations of certain implicit functions and differential equation solutions. However, McCormick's relaxations may be nonsmooth, and this nonsmoothness can create theoretical and computational obstacles when relaxations are to be deployed. This article presents a continuously differentiablemore » variant of McCormick's original relaxations in the multivariate McCormick framework of Tsoukalas and Mitsos. Gradients of the new differentiable relaxations may be computed efficiently using the standard forward or reverse modes of automatic differentiation. Furthermore, extensions to differentiable relaxations of implicit functions and solutions of parametric ordinary differential equations are discussed. A C++ implementation based on the library MC++ is described and applied to a case study in nonsmooth nonconvex optimization.« less

Differential Rationality and Personal Development.

ERIC Educational Resources Information Center

Fincher, Cameron

This publication discusses differential rationality; it asserts that the development of institutions, professions, and individuals involves the differentiation of forms and styles of thinking and knowing that are, in various ways, idiosyncratic. Based on this understanding, differential rationality can be seen as a developmental construct that…

Safety Studies for Use of Adipose Tissue‐Derived Mesenchymal Stromal/Stem Cells in a Rabbit Model for Osteoarthritis to Support a Phase I Clinical Trial

PubMed Central

Riester, Scott M.; Denbeigh, Janet M.; Lin, Yang; Jones, Dakota L.; de Mooij, Tristan; Lewallen, Eric A.; Nie, Hai; Paradise, Christopher R.; Radel, Darcie J.; Dudakovic, Amel; Camilleri, Emily T.; Larson, Dirk R.; Qu, Wenchun; Krych, Aaron J.; Frick, Matthew A.; Im, Hee‐Jeong; Dietz, Allan B.; Smith, Jay

2016-01-01

Abstract Adipose‐derived mesenchymal stem cells (AMSCs) offer potential as a therapeutic option for clinical applications in musculoskeletal regenerative medicine because of their immunomodulatory functions and capacity for trilineage differentiation. In preparation for a phase I clinical trial using AMSCs to treat patients with osteoarthritis, we carried out preclinical studies to assess the safety of human AMSCs within the intra‐articular joint space. Culture‐expanded human AMSCs grown in human platelet‐lysate were delivered via intra‐articular injections into normal healthy rabbit knees and knees at risk for the development of osteoarthritis after bilateral medial anterior hemimeniscectomy. Treatment outcomes and safety were evaluated by assessing the general health, function, and behavior of the animals. Joint tissues were analyzed by x‐ray, magnetic resonance imaging, and histopathology. Intra‐articular AMSC therapy was well tolerated in this study. We did not observe adverse systemic reactions, nor did we find evidence of damage to intra‐articular joint tissues. Thus, the data generated in this study show a favorable safety profile for AMSCs within the joint space in support of a phase I clinical trial evaluating the clinical utility of AMSCs to treat osteoarthritis. Stem Cells Translational Medicine 2017;6:910–922 PMID:28297568

5 CFR 532.511 - Environmental differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

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

Amyloid precursor protein expression and processing are differentially regulated during cortical neuron differentiation.

PubMed

Bergström, Petra; Agholme, Lotta; Nazir, Faisal Hayat; Satir, Tugce Munise; Toombs, Jamie; Wellington, Henrietta; Strandberg, Joakim; Bontell, Thomas Olsson; Kvartsberg, Hlin; Holmström, Maria; Boreström, Cecilia; Simonsson, Stina; Kunath, Tilo; Lindahl, Anders; Blennow, Kaj; Hanse, Eric; Portelius, Erik; Wray, Selina; Zetterberg, Henrik

2016-07-07

Amyloid precursor protein (APP) and its cleavage product amyloid β (Aβ) have been thoroughly studied in Alzheimer's disease. However, APP also appears to be important for neuronal development. Differentiation of induced pluripotent stem cells (iPSCs) towards cortical neurons enables in vitro mechanistic studies on human neuronal development. Here, we investigated expression and proteolytic processing of APP during differentiation of human iPSCs towards cortical neurons over a 100-day period. APP expression remained stable during neuronal differentiation, whereas APP processing changed. α-Cleaved soluble APP (sAPPα) was secreted early during differentiation, from neuronal progenitors, while β-cleaved soluble APP (sAPPβ) was first secreted after deep-layer neurons had formed. Short Aβ peptides, including Aβ1-15/16, peaked during the progenitor stage, while processing shifted towards longer peptides, such as Aβ1-40/42, when post-mitotic neurons appeared. This indicates that APP processing is regulated throughout differentiation of cortical neurons and that amyloidogenic APP processing, as reflected by Aβ1-40/42, is associated with mature neuronal phenotypes.

All-optical computation system for solving differential equations based on optical intensity differentiator.

PubMed

Tan, Sisi; Wu, Zhao; Lei, Lei; Hu, Shoujin; Dong, Jianji; Zhang, Xinliang

2013-03-25

We propose and experimentally demonstrate an all-optical differentiator-based computation system used for solving constant-coefficient first-order linear ordinary differential equations. It consists of an all-optical intensity differentiator and a wavelength converter, both based on a semiconductor optical amplifier (SOA) and an optical filter (OF). The equation is solved for various values of the constant-coefficient and two considered input waveforms, namely, super-Gaussian and Gaussian signals. An excellent agreement between the numerical simulation and the experimental results is obtained.

Intratemporal complications of otitis media.

PubMed

Maranhão, André Souza de Albuquerque; Andrade, José Santos Cruz de; Godofredo, Valéria Romero; Matos, Rafaella Caruso; Penido, Norma de Oliveira

2013-01-01

Otitis media (OM) is considered a potentially severe disease due to the risk of complications. To establish the annual incidence of intratemporal complications (ITC) resulting from OM and to prospectively assess patients for epidemiological and clinical factors. This prospective cohort study included patients admitted during one year at a university hospital diagnosed with intratemporal complications of OM. Patients were analyzed for age, gender, type of intratemporal complication, treatment, and clinical outcome. The overall incidence of complications and the specific incidence rates of each type of complication were determined. 1,816 patients were diagnosed with OM; 592 (33%) had chronic OM; 1224 (67%) had acute OM. Fifteen patients were diagnosed with OM ITC, adding up to an annual incidence of 0.8%. Nineteen diagnoses of ITC were made in 15 patients. Seven (36.8%) patients were diagnosed with labyrinthine fistula, five (26.3%) with mastoiditis, four (21.1%) with peripheral facial palsy, and three (15.8%) with labyrinthitis. The incidence of intratemporal complications remains significant when compared to the rates seen in developed countries. Chronic cholesteatomatous otitis media is the most frequent etiology of intratemporal complications. Labyrinthine fistula is the most common intratemporal complication.

Ocular counterrolling measured during eight hours of sustained body tilt

NASA Technical Reports Server (NTRS)

Miller, E. F., II; Graybiel, A.

1972-01-01

Adaptation of otolith organ activity was investigated by monitoring the ocular counterrolling response of four normal individuals and three persons with severe bilateral loss of labyrinthine function. Several eye photographs were recorded every 30 minutes during a period of 8 hours in which the subject was held in a lateral tilt (60 deg) position. The recorded eye roll position varied to an expected small extent within each test session; this variation about a given mean roll position was similar among the test sessions for all subjects. The mean roll position, on the other hand, changed from session to session in substantial amounts, but these changes appeared to be random with respect to time and among subjects. Furthermore, the intersessional variation in the mean torsional eye position of the normal subjects was equivalent to that of the labyrinthine-defective subjects who displayed little or no counterrolling. These results suggest that the human counterrolling response is maintained either by essentially nonadapting macular receptors or by extremely fine movements of the head in the gravitational field, such as may have been allowed by the biteboard/headrest restraint system used in this study, which served as an everchanging accelerative stimulus.

Acoustic schwannoma with intracochlear extension and primary intracochlear schwannoma: removal through translabyrinthine approach with facial bridge cochleostomy and transcanal approach.

PubMed

Mazzoni, A; Zanoletti, E; Faccioli, C; Martini, A

2017-05-01

Intracochlear schwannomas can occur either as an extension of a larger tumor from the internal auditory canal, or as a solitary labyrinthine tumor. They are currently removed via a translabyrinthine approach extended to the basal turn, adding a transotic approach for tumors lying beyond the basal turn. Facial bridge cochleostomy may be associated with the translabyrinthine approach to enable the whole cochlea to be approached without sacrificing the external auditory canal and tympanum. We describe seven cases, five of which underwent cochlear schwannoma resection with facial bridge cochleostomy, one case with the same procedure for a suspect tumor and one, previously subjected to radical tympanomastoidectomy, who underwent schwannoma resection via a transotic approach. Facial bridge cochleostomy involved removing the bone between the labyrinthine and tympanic portions of the fallopian canal, and exposing the cochlea from the basal to the apical turn. Patients' recovery was uneventful, and long-term magnetic resonance imaging showed no residual tumor. Facial bridge cochleostomy can be a flexible extension of the translabyrinthine approach for tumors extending from the internal auditory canal to the cochlea. The transcanal approach is suitable for the primary exclusive intralabyrinthine tumor. The indications for the different approaches are discussed.

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

ERIC Educational Resources Information Center

Tomlinson, Carol Ann; Strickland, Cindy A.

2005-01-01

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

Anomaly of the facial canal in a Mondini malformation with recurrent meningitis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Curtin, H.D.; Vignaud, J.; Bar, D.

1982-07-01

A patient with recurrent meningitis and congenital hearing loss was evaluated with tomography and metrizamide cisternography. Tomography showed an aberrant first portion of the facial nerve canal, while on cisternography, communication between the internal auditory canal and the dilated labyrinthine remnant was evident. The authors describe the radiographic findings and their significance and propose a mechanism for the formation of the anomalous facial nerve canal.

Nrf2 promotes neuronal cell differentiation.

PubMed

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

2009-09-15

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

Sumoylation Dynamics During Keratinocyte Differentiation

PubMed Central

Deyrieux, Adeline F.; Rosas-Acosta, Germán; Ozbun, Michelle A.; Wilson, Van G.

2012-01-01

Summary SUMO modification regulates the activity of numerous transcription factors that have a direct role in cell cycle progression, apoptosis, cellular proliferation, and development, but its role in differentiation processes is less clear. Keratinocyte differentiation requires the coordinated activation of a series of transcription factors, and as several critical keratinocyte transcription factors are known to be SUMO substrates, we investigated the role of sumoylation in keratinocyte differentiation. In a human keratinocyte cell line model (HaCaT cells), calcium-induced differentiation led to the transient and coordinated transcriptional activation of the genes encoding critical sumoylation system components, including SAE1, SAE2, Ubc9, SENP1, Miz-1 (PIASxβ), SUMO2, and SUMO3. The increased gene expression resulted in higher levels of the respective proteins and changes in the pattern of sumoylated substrate proteins during the differentiation process. Similar to the HaCaT results, stratified human foreskin keratinocytes showed an upregulation of Ubc9 in the suprabasal layers. Lastly, abrogation of sumoylation by Gam1 expression severely disrupted normal HaCaT differentiation, consistent with an important role for sumoylation in the proper progression of this biological process. PMID:17164289

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

ADVANTG Shielding Analysis for Closure Operations in an Open-Mode Repository

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bevill, Aaron M; Radulescu, Georgeta; Scaglione, John M

2013-01-01

en-mode repository concepts could require worker entry into access drifts after placement of fuel casks in order to perform activities related to backfill, plug emplacement, routine maintenance, or performance confirmation. An ideal emplacement-drift shielding configuration would minimize dose to workers while maximizing airflow through the emplacement drifts. This paper presents a preliminary investigation of the feasibility and effectiveness of radiation shielding concepts that could be employed to facilitate worker operations in an open-mode repository. The repository model for this study includes pressurized-water reactor fuel assemblies (60 GWd/MTU burnup, 40 year post-irradiation cooldown) in packages of 32 assemblies. The closest fuelmore » packages are 5 meters from dosimetry voxels in the access drift. The unshielded dose to workers in the access drift is 73.7 rem/hour. Prior work suggests that open-mode repository concepts similar to this one would require 15 m3/s of ventilation airflow. Shielding concepts considered here include partial concrete plugs, labyrinthine shields, and stainless steel photon attenuator grids. Maximum dose to workers in the access drift was estimated for each shielding concept using MCNP5 with variance reduction parameters generated by ADVANTG. Because airflow through the shielding is important for open-mode repositories, a semi-empirical estimate of the head loss due to each shielding configuration was also calculated. Airflow and shielding performance vary widely among the proposed shielding configurations. Although the partial plug configuration had the best airflow performance, it allowed dose rates 1500 greater than the specified target. Labyrinthine shielding concepts yield doses on the order of 1 mrem/hour with configurations that impose 3 to 11 J/kg head loss. Adding 1 cm lead lining to the airflow channels of labyrinthine designs further reduces the worker dose by 65% to 95%. Photon-attenuator concepts may reduce

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…

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

PubMed

Sun, Leping

2016-01-01

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

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

PubMed Central

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

2014-01-01

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

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…

Differential growth factor control of bone formation through osteoprogenitor differentiation.

PubMed

Chaudhary, L R; Hofmeister, A M; Hruska, K A

2004-03-01

The osteogenic factors bone morphogenetic protein (BMP-7), platelet-derived growth factor (PDGF)-BB, and fibroblast growth factor (FGF-2) regulate the recruitment of osteoprogenitor cells and their proliferation and differentiation into mature osteoblasts. However, their mechanisms of action on osteoprogenitor cell growth, differentiation, and bone mineralization remain unclear. Here, we tested the hypothesis that these osteogenic agents were capable of regulating osteoblast differentiation and bone formation in vitro. Normal human bone marrow stromal (HBMS) cells were treated with BMP-7 (40 ng ml(-1)), PDGF-BB (20 ng ml(-1)), FGF-2 (20 ng ml(-1)), or FGF-2 plus BMP-7 for 28 days in a serum-containing medium with 10 mM beta-glycerophosphate and 50 microg ml(-1) ascorbic acid. BMP-7 stimulated a morphological change to cuboidal-shaped cells, increased alkaline phosphatase (ALKP) activity, bone sialoprotein (BSP) gene expression, and alizarin red S positive nodule formation. Hydroxyapatite (HA) crystal deposition in the nodules was demonstrated by Fourier transform infrared (FTIR) spectroscopy only in BMP-7- and dexamethasone (DEX)-treated cells. DEX-treated cells appeared elongated and fibroblast-like compared to BMP-7-treated cells. FGF-2 did not stimulate ALKP, and cell morphology was dystrophic. PDGF-BB had little or no effect on ALKP activity and biomineralization. Alizarin Red S staining of cells and calcium assay indicated that BMP-7, DEX, and FGF-2 enhanced calcium mineral deposition, but FTIR spectroscopic analysis demonstrated no formation of HA similar to human bone in control, PDGF-BB-, and FGF-2-treated samples. Thus, FGF-2 stimulated amorphous octacalcium phosphate mineral deposition that failed to mature into HA. Interestingly, FGF-2 abrogated BMP-7-induced ALKP activity and HA formation. Results demonstrate that BMP-7 was competent as a sole factor in the differentiation of human bone marrow stromal cells to bone-forming osteoblasts confirmed by FTIR

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.

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.

A genome-wide methylation study on obesity: differential variability and differential methylation.

PubMed

Xu, Xiaojing; Su, Shaoyong; Barnes, Vernon A; De Miguel, Carmen; Pollock, Jennifer; Ownby, Dennis; Shi, Hidong; Zhu, Haidong; Snieder, Harold; Wang, Xiaoling

2013-05-01

Besides differential methylation, DNA methylation variation has recently been proposed and demonstrated to be a potential contributing factor to cancer risk. Here we aim to examine whether differential variability in methylation is also an important feature of obesity, a typical non-malignant common complex disease. We analyzed genome-wide methylation profiles of over 470,000 CpGs in peripheral blood samples from 48 obese and 48 lean African-American youth aged 14-20 y old. A substantial number of differentially variable CpG sites (DVCs), using statistics based on variances, as well as a substantial number of differentially methylated CpG sites (DMCs), using statistics based on means, were identified. Similar to the findings in cancers, DVCs generally exhibited an outlier structure and were more variable in cases than in controls. By randomly splitting the current sample into a discovery and validation set, we observed that both the DVCs and DMCs identified from the first set could independently predict obesity status in the second set. Furthermore, both the genes harboring DMCs and the genes harboring DVCs showed significant enrichment of genes identified by genome-wide association studies on obesity and related diseases, such as hypertension, dyslipidemia, type 2 diabetes and certain types of cancers, supporting their roles in the etiology and pathogenesis of obesity. We generalized the recent finding on methylation variability in cancer research to obesity and demonstrated that differential variability is also an important feature of obesity-related methylation changes. Future studies on the epigenetics of obesity will benefit from both statistics based on means and statistics based on variances.

Perceptual dimensions differentiate emotions.

PubMed

Cavanaugh, Lisa A; MacInnis, Deborah J; Weiss, Allen M

2015-08-26

Individuals often describe objects in their world in terms of perceptual dimensions that span a variety of modalities; the visual (e.g., brightness: dark-bright), the auditory (e.g., loudness: quiet-loud), the gustatory (e.g., taste: sour-sweet), the tactile (e.g., hardness: soft vs. hard) and the kinaesthetic (e.g., speed: slow-fast). We ask whether individuals use perceptual dimensions to differentiate emotions from one another. Participants in two studies (one where respondents reported on abstract emotion concepts and a second where they reported on specific emotion episodes) rated the extent to which features anchoring 29 perceptual dimensions (e.g., temperature, texture and taste) are associated with 8 emotions (anger, fear, sadness, guilt, contentment, gratitude, pride and excitement). Results revealed that in both studies perceptual dimensions differentiate positive from negative emotions and high arousal from low arousal emotions. They also differentiate among emotions that are similar in arousal and valence (e.g., high arousal negative emotions such as anger and fear). Specific features that anchor particular perceptual dimensions (e.g., hot vs. cold) are also differentially associated with emotions.

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…

Numerical Differentiation of Noisy, Nonsmooth Data

DOE PAGES

Chartrand, Rick

2011-01-01

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

Lifting the Differentiation Embargo.

PubMed

Latif, Anne-Louise; Holyoake, Tessa L

2016-09-22

Effective differentiation therapy for acute myeloid leukemia (AML) has been restricted to a small subset of patients with one defined genetic abnormality. Using an unbiased small molecule screen, Sykes et al. now identify a mechanism of de-repression of differentiation in several models of AML driven by distinct genetic drivers. Copyright © 2016 Elsevier Inc. All rights reserved.

Emotion differentiation dissected: between-category, within-category, and integral emotion differentiation, and their relation to well-being.

PubMed

Erbas, Yasemin; Ceulemans, Eva; Blanke, Elisabeth S; Sels, Laura; Fischer, Agneta; Kuppens, Peter

2018-04-24

Emotion differentiation, the ability to describe and label our own emotions in a differentiated and specific manner, has been repeatedly associated with well-being. However, it is unclear exactly what type of differentiation is most strongly related to well-being: the ability to make fine-grained distinctions between emotions that are relatively closely related (e.g. anger and irritation), the ability to make larger distinctions between very distinct emotions (e.g. anger and sadness), or the combination of both. To determine which type of differentiation is most predictive of well-being, we performed a comprehensive meta-analysis across six datasets. We examined the correlations between these three types of differentiation and several indicators of well-being (depression, emotional clarity, and self-esteem). Results showed that individuals differentiated most between very distinct emotions and least between more related emotions, and that an index computed across emotions from both the same and different emotion categories was most strongly associated with well-being indicators.

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,…

Differential DNases are selectively used in neuronal apoptosis depending on the differentiation state.

PubMed

Shiokawa, D; Tanuma, S

2004-10-01

In this study, we investigate the roles of two apoptotic endonucleases, CAD and DNase gamma, in neuronal apoptosis. High expression of CAD, but not DNase gamma, is detected in proliferating N1E-115 neuroblastoma cells, and apoptotic DNA fragmentation induced by staurosporine under proliferating conditions is abolished by the expression of a caspase-resistant form of ICAD. After the induction of neuronal differentiation, CAD disappearance and the induction of DNase gamma occur simultaneously in N1E-115 cells. Apoptotic DNA fragmentation that occurs under differentiating conditions is suppressed by the downregulation of DNase gamma caused by its antisense RNA. The induction of DNase gamma is also observed during neuronal differentiation of PC12 cells, and apoptotic DNA fragmentation induced by NGF deprivation is inhibited by the antisense-mediated downregulation of DNase gamma. These observations suggest that DNA fragmentation in neuronal apoptosis is catalyzed by either CAD or DNase gamma depending on the differentiation state. Furthermore, DNase gamma is suggested to be involved in naturally occurring apoptosis in developing nervous systems.

Differentiation of Spermatogonia Stem Cells into Functional Mature Neurons Characterized with Differential Gene Expression.

PubMed

Bojnordi, Maryam Nazm; Azizi, Hossein; Skutella, Thomas; Movahedin, Mansoureh; Pourabdolhossein, Fereshteh; Shojaei, Amir; Hamidabadi, Hatef Ghasemi

2017-09-01

Transplantation of embryonic stem cells (ESCs) is a promising therapeutic approach for the treatment of neurodegenerative diseases. However, ESCs are not usable clinically due to immunological and ethical limitations. The identification of an alternative safe cell source opens novel options via autologous transplantation in neuro-regeneration circumventing these problems. Here, we examined the neurogenic capacity of embryonic stem-like cells (ES-like cells) derived from the testis using neural growth factor inducers and utilized them to generate functional mature neurons. The neuronal differentiation of ES-like cells is induced in three stages. Stage 1 is related to embryoid body (EB) formation. To induce neuroprogenitor cells, EBs were cultured in the presence of retinoic acid, N 2 supplement and fibroblast growth factor followed by culturing in a neurobasal medium containing B 27 , N 2 supplements for additional 10 days, to allow the maturation and development of neuronal progenitor cells. The neurogenic differentiation was confirmed by immunostaining for markers of mature neurons. The differentiated neurons were positive for Tuj1 and Tau1. Real-time PCR dates indicated the expression of Nestin and Neuro D (neuroprogenitor markers) in induced cells at the second stage of the differentiation protocol. The differentiated mature neurons exhibited the specific neuron markers Map2 and β-tubulin. The functional maturity of neurons was confirmed by an electrophysiological analysis of passive and active neural membrane properties. These findings indicated a differentiation capacity of ES-like cells derived from the testis to functionally mature neurons, which proposes them as a novel cell source for neuroregenerative medicine.

Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation

PubMed Central

Wang, Xiaoqin; Omar, Omar; Vazirisani, Forugh; Thomsen, Peter

2018-01-01

Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as “Wnt signalling pathway” and “endocytosis”. Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA. PMID:29447276

5 CFR 532.511 - Environmental differentials.

Code of Federal Regulations, 2010 CFR

2010-01-01

... in a pay status on the day on which he/she is exposed to the situation. (4) An employee may not be... 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 States...

Reticulated acanthoma with sebaceous differentiation mimicking melanoma

PubMed Central

Ribeiro, Felipe; Leocadia, Elizabeth; Macarenco, Ricardo S.; Lapins, Jan; Huet, Pascale; Akay, Bengu Nisa; Steiner, Denise

2017-01-01

Reticulated acanthoma with sebaceous differentiation (RASD) is a rare, benign cutaneous tumor with peculiar histopathologic characteristics [1]. RASD had been described under various synonyms such as superficial epithelioma with sebaceous differentiation, sebocrine adenoma, poroma with sebaceous differentiation, and seborrheic keratosis with sebaceous differentiation [2]. Clinical differential diagnosis of RASD includes cutaneous superficial epithelial neoplasia such as Bowen’s disease, superficial basal cell carcinoma (BCC) and intraepidermal eccrine poroma [1]. We report the first case of RASD mimicking both clinically and dermoscopically a melanoma. PMID:29085717

Smell differential reactivity, but not taste differential reactivity, is related to food neophobia in toddlers.

PubMed

Monnery-Patris, Sandrine; Wagner, Sandra; Rigal, Natalie; Schwartz, Camille; Chabanet, Claire; Issanchou, Sylvie; Nicklaus, Sophie

2015-12-01

Previous research has identified relationships between chemosensory reactivity and food neophobia in children. However, most studies have investigated this relationship using declarative data and without separately analysing smell and taste reactivity. Our first objective was to assess the relationships between smell and taste differential reactivity in toddlers (i.e. reactivity towards several stimuli), using experimental behavioural measurements. The second objective was to determine the relationships between smell (or taste) differential reactivity and food neophobia in toddlers, with the hypothesis that the more responsive a toddler was across food odours or tastes, the more neophobic s/he would be. An additional objective was to determine whether the potential relationships between smell (or taste) differential reactivity and food neophobia differ according to gender. One hundred and twenty-three toddlers aged from 20 to 22 months from the Opaline birth cohort (Observatory of Food Preferences in Infants and Children) were involved. A questionnaire was used to assess child's food neophobia. Toddlers' differential reactivity for smell (and for taste) was defined as the variability of behavioural responses over 8 odorants, and over the five basic tastes. Smell and taste differential reactivities were not correlated. Food neophobia scores were modestly but significantly positively correlated with smell differential reactivity but not with taste differential reactivity. When gender was considered, smell reactivity and neophobia were correlated only among boys. This indicates the need to study smell and taste reactivity separately to determine their associations with eating behaviours. This suggests that the rejection of novel foods in neophobic boys could be partly due to food odour. This finding is new and clearly requires further investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

PubMed

Randau, Thomas M; Schildberg, Frank A; Alini, Mauro; Wimmer, Matthias D; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J

2013-01-01

The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal

Legendre-tau approximations for functional differential equations

NASA Technical Reports Server (NTRS)

Ito, K.; Teglas, R.

1986-01-01

The numerical approximation of solutions to linear retarded functional differential equations are considered using the so-called Legendre-tau method. The functional differential equation is first reformulated as a partial differential equation with a nonlocal boundary condition involving time-differentiation. The approximate solution is then represented as a truncated Legendre series with time-varying coefficients which satisfy a certain system of ordinary differential equations. The method is very easy to code and yields very accurate approximations. Convergence is established, various numerical examples are presented, and comparison between the latter and cubic spline approximation is made.

Legendre-Tau approximations for functional differential equations

NASA Technical Reports Server (NTRS)

Ito, K.; Teglas, R.

1983-01-01

The numerical approximation of solutions to linear functional differential equations are considered using the so called Legendre tau method. The functional differential equation is first reformulated as a partial differential equation with a nonlocal boundary condition involving time differentiation. The approximate solution is then represented as a truncated Legendre series with time varying coefficients which satisfy a certain system of ordinary differential equations. The method is very easy to code and yields very accurate approximations. Convergence is established, various numerical examples are presented, and comparison between the latter and cubic spline approximations is made.

MEK5 suppresses osteoblastic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kaneshiro, Shoichi; Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871; Otsuki, Dai

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, osteocalcinmore » (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.« less

The role of SOCS3 in modulating leukaemia inhibitory factor signalling during murine placental development

PubMed Central

Boyle, Kristy; Robb, Lorraine

2008-01-01

Cytokines are an integral part of the adaptive and innate immune responses. The signalling pathways triggered by receptor engagement translate exposure to cytokine into a coordinated biological response. To contain these responses, the initiation, duration and magnitude of the signal is controlled at multiple levels. SOCS (suppressor of cytokine signalling) proteins act in a negative feedback loop to inhibit signal transduction. Mice with a deletion of SOCS3 die at midgestion due to placental insufficiency. SOCS3-null placentae have increased numbers of mature trophoblast giant cells, disruption of the labyrinthine layer and a decrease in the spongiotrophoblast layer. Genetic crosses have revealed that the phenotype is due to dysregulation of signalling downstream of the leukaemia inhibitory factor (LIF) receptor alpha (LIFRα) and that the ligand responsible for this, LIF, is produced by embryonic tissues and acts in a paracrine fashion. These observations highlight the role of LIF as an extrinsic factor regulating trophoblast differentiation in vivo. The creation of mice with conditional deletion of SOCS3 in different tissues has also uncovered critical roles for SOCS3 in the regulation of IL-6, G-CSF and leptin signalling. PMID:17408753

The role of SOCS3 in modulating leukaemia inhibitory factor signalling during murine placental development.

PubMed

Boyle, Kristy; Robb, Lorraine

2008-01-01

Cytokines are an integral part of the adaptive and innate immune responses. The signalling pathways triggered by receptor engagement translate exposure to cytokine into a coordinated biological response. To contain these responses, the initiation, duration and magnitude of the signal is controlled at multiple levels. Suppressor of cytokine signalling (SOCS) proteins act in a negative feedback loop to inhibit signal transduction. Mice with a deletion of SOCS3 die at midgestion due to placental insufficiency. SOCS3-null placentae have increased numbers of mature trophoblast giant cells, disruption of the labyrinthine layer and a decrease in the spongiotrophoblast layer. Genetic crosses have revealed that the phenotype is due to dysregulation of signalling downstream of the leukaemia inhibitory factor (LIF) receptor alpha (LIFRalpha) and that the ligand responsible for this, LIF, is produced by embryonic tissues and acts in a paracrine fashion. These observations highlight the role of LIF as an extrinsic factor regulating trophoblast differentiation in vivo. The creation of mice with conditional deletion of SOCS3 in different tissues has also uncovered critical roles for SOCS3 in the regulation of IL-6, G-CSF and leptin signalling.

Human Adipose-Derived Stem Cells Labeled with Plasmonic Gold Nanostars for Cellular Tracking and Photothermal Cancer Cell Ablation.

PubMed

Shammas, Ronnie L; Fales, Andrew M; Crawford, Bridget M; Wisdom, Amy J; Devi, Gayathri R; Brown, David A; Vo-Dinh, Tuan; Hollenbeck, Scott T

2017-04-01

Gold nanostars are unique nanoplatforms that can be imaged in real time and transform light energy into heat to ablate cells. Adipose-derived stem cells migrate toward tumor niches in response to chemokines. The ability of adipose-derived stem cells to migrate and integrate into tumors makes them ideal vehicles for the targeted delivery of cancer nanotherapeutics. To test the labeling efficiency of gold nanostars, undifferentiated adipose-derived stem cells were incubated with gold nanostars and a commercially available nanoparticle (Qtracker), then imaged using two-photon photoluminescence microscopy. The effects of gold nanostars on cell phenotype, proliferation, and viability were assessed with flow cytometry, 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide metabolic assay, and trypan blue, respectively. Trilineage differentiation of gold nanostar-labeled adipose-derived stem cells was induced with the appropriate media. Photothermolysis was performed on adipose-derived stem cells cultured alone or in co-culture with SKBR3 cancer cells. Efficient uptake of gold nanostars occurred in adipose-derived stem cells, with persistence of the luminescent signal over 4 days. Labeling efficiency and signal quality were greater than with Qtracker. Gold nanostars did not affect cell phenotype, viability, or proliferation, and exhibited stronger luminescence than Qtracker throughout differentiation. Zones of complete ablation surrounding the gold nanostar-labeled adipose-derived stem cells were observed following photothermolysis in both monoculture and co-culture models. Gold nanostars effectively label adipose-derived stem cells without altering cell phenotype. Once labeled, photoactivation of gold nanostar-labeled adipose-derived stem cells ablates neighboring cancer cells, demonstrating the potential of adipose-derived stem cells as a vehicle for the delivery of site-specific cancer therapy.

A Novel Porcine Model for Future Studies of Cell-enriched Fat Grafting

PubMed Central

Sørensen, Celine L.; Vester-Glowinski, Peter V.; Herly, Mikkel; Kurbegovic, Sorel; Ørholt, Mathias; Svalgaard, Jesper D.; Kølle, Stig-Frederik T.; Kristensen, Annemarie T.; Talman, Maj-Lis M.; Drzewiecki, Krzysztof T.; Fischer-Nielsen, Anne

2018-01-01

Background: Cell-enriched fat grafting has shown promising results for improving graft survival, although many questions remain unanswered. A large animal model is crucial for bridging the gap between rodent studies and human trials. We present a step-by-step approach in using the Göttingen minipig as a model for future studies of cell-enriched large volume fat grafting. Methods: Fat grafting was performed as bolus injections and structural fat grafting. Graft retention was assessed by magnetic resonance imaging after 120 days. The stromal vascular fraction (SVF) was isolated from excised fat and liposuctioned fat from different anatomical sites and analyzed. Porcine adipose-derived stem/stromal cells (ASCs) were cultured in different growth supplements, and population doubling time, maximum cell yield, expression of surface markers, and differentiation potential were investigated. Results: Structural fat grafting in the breast and subcutaneous bolus grafting in the abdomen revealed average graft retention of 53.55% and 15.28%, respectively, which are similar to human reports. Liposuction yielded fewer SVF cells than fat excision, and abdominal fat had the most SVF cells/g fat with SVF yields similar to humans. Additionally, we demonstrated that porcine ASCs can be readily isolated and expanded in culture in allogeneic porcine platelet lysate and fetal bovine serum and that the use of 10% porcine platelet lysate or 20% fetal bovine serum resulted in population doubling time, maximum cell yield, surface marker profile, and trilineage differentiation that were comparable with humans. Conclusions: The Göttingen minipig is a feasible and cost-effective, large animal model for future translational studies of cell-enriched fat grafting. PMID:29876178

Differentiation of Cognitive Abilities across the Lifespan

PubMed Central

Tucker-Drob, Elliot M.

2009-01-01

Existing representations of cognitive ability structure are exclusively based on linear patterns of interrelations. However, a number of developmental and cognitive theories predict that abilities are differentially related across ages (age differentiation-dedifferentiation) and across levels of functioning (ability differentiation). Nonlinear factor analytic models were applied to multivariate cognitive ability data from 6,273 individuals, ages 4 to 101 years, who were selected to be nationally representative of the United States population. Results consistently supported ability differentiation, but were less clear with respect to age differentiation-dedifferentiation. Little evidence for age modification of ability differentiation was found. These findings are particularly informative about the nature of individual differences in cognition, and the developmental course of cognitive ability level and structure. PMID:19586182

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.

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.

Differentiating the World History Course.

ERIC Educational Resources Information Center

Lasher, Mary E.

1986-01-01

An honors world history course for gifted tenth graders compacted traditional content while offering differential reading materials and content as well as differentiated skill development. Unusual activities, such as international feast and historical persons party, stressed divergent thinking. (CL)

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

DOEpatents

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

2007-03-06

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

Enhancer and Transcription Factor Dynamics during Myeloid Differentiation Reveal an Early Differentiation Block in Cebpa null Progenitors.

PubMed

Pundhir, Sachin; Bratt Lauridsen, Felicia Kathrine; Schuster, Mikkel Bruhn; Jakobsen, Janus Schou; Ge, Ying; Schoof, Erwin Marten; Rapin, Nicolas; Waage, Johannes; Hasemann, Marie Sigurd; Porse, Bo Torben

2018-05-29

Transcription factors PU.1 and CEBPA are required for the proper coordination of enhancer activity during granulocytic-monocytic (GM) lineage differentiation to form myeloid cells. However, precisely how these factors control the chronology of enhancer establishment during differentiation is not known. Through integrated analyses of enhancer dynamics, transcription factor binding, and proximal gene expression during successive stages of murine GM-lineage differentiation, we unravel the distinct kinetics by which PU.1 and CEBPA coordinate GM enhancer activity. We find no evidence of a pioneering function of PU.1 during late GM-lineage differentiation. Instead, we delineate a set of enhancers that gain accessibility in a CEBPA-dependent manner, suggesting a pioneering function of CEBPA. Analyses of Cebpa null bone marrow demonstrate that CEBPA controls PU.1 levels and, unexpectedly, that the loss of CEBPA results in an early differentiation block. Taken together, our data provide insights into how PU.1 and CEBPA functionally interact to drive GM-lineage differentiation. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

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

ERIC Educational Resources Information Center

Hewitt, Kimberly Kappler; Weckstein, Daniel K.

2011-01-01

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

Anti-differentiation non-coding RNA, ANCR, is differentially expressed in different types of brain tumors.

PubMed

Malakootian, Mahshid; Mirzadeh Azad, Fatemeh; Fouani, Youssef; Taheri Bajgan, Elham; Saberi, Hooshang; Mowla, Seyed Javad

2018-06-01

Long non-coding RNAs (lncRNAs) are important modulators of various cellular and molecular events, including cancer-associated pathways. The Anti-differentiation ncRNA (ANCR) is a key regulator of keratinocyte differentiation, where its expression is necessary to maintain epidermal progenitor's cells. Herein, we investigated the expression pattern of ANCR in the course of neural differentiation. Moreover, we used published RNAseq data and clinical samples to evaluate the alteration of ANCR expression in different cell types and brain tumors. Furthermore, we manipulated ANCR expression in glioma cell lines to clarify a potential functional role for ANCR in tumorigenesis. Our qRT-PCR results revealed a significant upregulation of ANCR in more malignant and less differentiated types of brain tumors (P = 0.03). This data was in accordance with down regulation of ANCR during neural differentiation. ANCR suppression caused an elevation in apoptosis rate, as well as a G1 cell cycle arrest in glioblastoma cell line. Altogether, our data demonstrated that ANCR may play a role in glioma genesis and that it could be considered as a potential diagnostic and therapeutic target to combat brain cancers.

Focal high cell density generates a gradient of patterns in self-organizing vascular mesenchymal cells.

PubMed

Cheng, Henry; Reddy, Aneela; Sage, Andrew; Lu, Jinxiu; Garfinkel, Alan; Tintut, Yin; Demer, Linda L

2012-01-01

In embryogenesis, structural patterns, such as vascular branching, may form via a reaction-diffusion mechanism in which activator and inhibitor morphogens guide cells into periodic aggregates. We previously found that vascular mesenchymal cells (VMCs) spontaneously aggregate into nodular structures and that morphogen pairs regulate the aggregation into patterns of spots and stripes. To test the effect of a focal change in activator morphogen on VMC pattern formation, we created a focal zone of high cell density by plating a second VMC layer within a cloning ring over a confluent monolayer. After 24 h, the ring was removed and pattern formation monitored by phase-contrast microscopy. At days 2-8, the patterns progressed from uniform distributions to swirl, labyrinthine and spot patterns. Within the focal high-density zone (HDZ) and a narrow halo zone, cells aggregated into spot patterns, whilst in the outermost zone of the plate, cells formed a labyrinthine pattern. The area occupied by aggregates was significantly greater in the outermost zone than in the HDZ or halo. The rate of pattern progression within the HDZ increased as a function of its plating density. Thus, focal differences in cell density may drive pattern formation gradients in tissue architecture, such as vascular branching. Copyright © 2012 S. Karger AG, Basel.

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.

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.

Cross-differential amplifier

NASA Technical Reports Server (NTRS)

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

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.

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.

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

ERIC Educational Resources Information Center

Haelermans, Carla; Ghysels, Joris; Prince, Fernao

2015-01-01

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

Precise automatic differential stellar photometry

NASA Technical Reports Server (NTRS)

Young, Andrew T.; Genet, Russell M.; Boyd, Louis J.; Borucki, William J.; Lockwood, G. Wesley

1991-01-01

The factors limiting the precision of differential stellar photometry are reviewed. Errors due to variable atmospheric extinction can be reduced to below 0.001 mag at good sites by utilizing the speed of robotic telescopes. Existing photometric systems produce aliasing errors, which are several millimagnitudes in general but may be reduced to about a millimagnitude in special circumstances. Conventional differential photometry neglects several other important effects, which are discussed in detail. If all of these are properly handled, it appears possible to do differential photometry of variable stars with an overall precision of 0.001 mag with ground based robotic telescopes.

Glycoproteomic Analysis of Glioblastoma Stem Cell Differentiation

PubMed Central

He, Jintang; Liu, Yashu; Zhu, Thant S.; Xie, Xiaolei; Costello, Mark A.; Talsma, Caroline E.; Flack, Callie G.; Crowley, Jessica G.; DiMeco, Francesco; Vescovi, Angelo L.; Fan, Xing; Lubman, David M.

2010-01-01

Cancer stem cells are responsible for tumor formation through self-renewal and differentiation into multiple cell types, and thus represent a new therapeutic target for tumors. Glycoproteins play a critical role in determining the fates of stem cells such as self-renewal, proliferation and differentiation. Here we applied a multi-lectin affinity chromatography and quantitative glycoproteomics approach to analyze alterations of glycoproteins relevant to the differentiation of a glioblastoma-derived stem cell line HSR-GBM1. Three lectins including concanavalin A (Con A), wheat germ agglutinin (WGA) and peanut agglutinin (PNA) were used to capture glycoproteins, followed by LC-MS/MS analysis. A total of 73 and 79 high-confidence (FDR < 0.01) glycoproteins were identified from the undifferentiated and differentiated cells, respectively. Label-free quantitation resulted in the discovery of 18 differentially expressed glycoproteins, wherein 9 proteins are localized in the lysosome. All of these lysosomal glycoproteins were up-regulated after differentiation, where their principal function was hydrolysis of glycosyl residues. Protein-protein interaction and functional analyses revealed the active involvement of lysosomes during the process of glioblastoma stem cell differentiation. This work provides glycoprotein markers to characterize differentiation status of glioblastoma stem cells which may be useful in stemcell therapy of glioblastoma. PMID:21110520

Pleiotrophin antagonizes Brd2 during neuronal differentiation

PubMed Central

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

2014-01-01

ABSTRACT Bromodomain-containing protein 2 (Brd2) is a BET family chromatin adaptor required for expression of cell-cycle-associated genes and therefore involved in cell cycle progression. Brd2 is expressed in proliferating neuronal progenitors, displays cell-cycle-stimulating activity and, when overexpressed, impairs neuronal differentiation. Paradoxically, Brd2 is also detected in differentiating neurons. To shed light on the role of Brd2 in the transition from cell proliferation to differentiation, we had previously looked for proteins that interacted with Brd2 upon induction of neuronal differentiation. Surprisingly, we identified the growth factor pleiotrophin (Ptn). Here, we show that Ptn antagonized the cell-cycle-stimulating activity associated with Brd2, thus enhancing induced neuronal differentiation. Moreover, Ptn knockdown reduced neuronal differentiation. We analyzed Ptn-mediated antagonism of Brd2 in a cell differentiation model and in two embryonic processes associated with the neural tube: spinal cord neurogenesis and neural crest migration. Finally, we investigated the mechanisms of Ptn-mediated antagonism and determined that Ptn destabilizes the association of Brd2 with chromatin. Thus, Ptn-mediated Brd2 antagonism emerges as a modulation system accounting for the balance between cell proliferation and differentiation in the vertebrate nervous system. PMID:24695857

Dielectric metasurfaces solve differential and integro-differential equations.

PubMed

Abdollahramezani, Sajjad; Chizari, Ata; Dorche, Ali Eshaghian; Jamali, Mohammad Vahid; Salehi, Jawad A

2017-04-01

Leveraging subwavelength resonant nanostructures, plasmonic metasurfaces have recently attracted much attention as a breakthrough concept for engineering optical waves both spatially and spectrally. However, inherent ohmic losses concomitant with low coupling efficiencies pose fundamental impediments over their practical applications. Not only can all-dielectric metasurfaces tackle such substantial drawbacks, but also their CMOS-compatible configurations support both Mie resonances that are invariant to the incident angle. Here, we report on a transmittive metasurface comprising arrayed silicon nanodisks embedded in a homogeneous dielectric medium to manipulate phase and amplitude of incident light locally and almost independently. By taking advantage of the interplay between the electric/magnetic resonances and employing general concepts of spatial Fourier transformation, a highly efficient metadevice is proposed to perform mathematical operations including solution of ordinary differential and integro-differential equations with constant coefficients. Our findings further substantiate dielectric metasurfaces as promising candidates for miniaturized, two-dimensional, and planar optical analog computing systems that are much thinner than their conventional lens-based counterparts.

[Atypical chronic myeloid leukemia presenting with trilineage dysplasia and IgG (lambda) type monoclonal gammopathy].

PubMed

Itoh, K; Kashimura, T; Kobayashi, Y; Yagasaki, F; Sakata, T; Kawai, N; Matsuda, A; Kusumoto, S; Fukuda, M; Ino, H; Murohashi, I; Jinnai, I; Yoshida, S; Bessho, M; Saitoh, M; Hirashima, K

1999-02-01

A 78-year-old man was diagnosed as leukocytosis in February 1994. Physical examination revealed marked hepatosplenomegaly. A peripheral blood examination disclosed 95,090/microliter leukocytes without hiatus leukemicus, 6.5 g/dl Hb, and 15.0 x 10(4)/microliter platelets. The neutrophil alkaline phosphatase score was 27, and serum VB12 was above 1,600pg/ml. IgG was identified as monoclonal immunoglobulin of type lambda. Bone marrow specimens demonstrated marked granulocytic hyperplasia. Neither the Philadelphia chromosome (Ph1) nor BCR gene rearrangement was detected; hence, the diagnosis of Ph1 (-) chronic myeloid leukemia (CML) was made. The patient was treated with hydroxyurea and low-dose VP-16 with no improvement, and died of pneumonia and sepsis in June 1995. This case was considered to be consistent with atypical CML (aCML) according to the FAB classification because monocytosis was not observed. It seems likely and interesting that the coexistent monoclonal gammopathy and aCML might have arisen from common abnormal hematopoietic stem cells.

Intelligence Differentiation in Adult Samples.

ERIC Educational Resources Information Center

Abad, Francisco J.; Colom, Robert; Juan-Espinosa, Manuel; Garcia, Luis F.

2003-01-01

Results for 3,340 participants taking a battery of cognitive tests and an analysis of the Spanish standardization of the Wechsler Adult Intelligence Scale-III support the differentiation of intelligence across the range of ability, with WAIS-III results more supportive of the differentiation theory. (SLD)

Histologic findings in skin biopsy in a JMML rash: a case report and review of literature.

PubMed

Gupta, Rajib K; Qureshi, Amna; Choi, John K

2014-01-01

Juvenile myelomonocytic leukemia (JMML), belonging to the category of myeloproliferative/myelodysplastic syndromes, is a rare pediatric hematologic malignancy with frequent skin manifestations commonly in the form of rashes. However, these rashes are not always biopsied and their immunophenotype studied in details. We report one such case in a 2-year-old boy who presented with a 1-month history of nonresolving fever, fatigue, and pallor along with a generalized maculopapular skin rash. The child also had mild hepatomegaly. A complete blood count with differential revealed a hemoglobin value of 8.6 g/L, leukocytosis (white blood cell count of 55.3 × 109/L), absolute monocytosis (27 × 109/L), immature granulocytes, and a platelet count of 126 × 109/L. The bone marrow aspirate showed a hypercellular marrow with trilineage hematopoiesis, 10% blasts (including promonocytes), increased monocytes (46%), and dysplastic changes in the erythroid and myeloid cell lines. These findings along with absence of a BCR-ABL1 fusion gene and a hemoglobin F level of 3.4% were consistent with the diagnosis of JMML, which was confirmed by subsequent positive granulocyte macrophage-colony stimulating factor hypersensitivity and NRAS mutation studies. A skin biopsy of the rash revealed a dermal infiltrate composed predominantly of atypical monocytic cells that were positive for CD68, myeloperoxidase, and lysozyme and negative for CD117, CD1a, and S100, consistent with JMML.

MicroRNA profiling reveals unique miRNA signatures in IGF-1 treated embryonic striatal stem cell fate decisions in striatal neurogenesis in vitro.

PubMed

Pati, Soumya; Supeno, Nor Entan; Muthuraju, Sangu; Abdul Hadi, Raisah; Ghani, Abdul Rahman Izaini; Idris, Fauziah Mohamad; Maletic-Savatic, Mirjana; Abdullah, Jafri Malin; Jaafar, Hasnan

2014-01-01

The striatum is considered to be the central processing unit of the basal ganglia in locomotor activity and cognitive function of the brain. IGF-1 could act as a control switch for the long-term proliferation and survival of EGF+bFGF-responsive cultured embryonic striatal stem cell (ESSC), while LIF imposes a negative impact on cell proliferation. The IGF-1-treated ESSCs also showed elevated hTERT expression with demonstration of self-renewal and trilineage commitment (astrocytes, oligodendrocytes, and neurons). In order to decipher the underlying regulatory microRNA (miRNA)s in IGF-1/LIF-treated ESSC-derived neurogenesis, we performed in-depth miRNA profiling at 12 days in vitro and analyzed the candidates using the Partek Genome Suite software. The annotated miRNA fingerprints delineated the differential expressions of miR-143, miR-433, and miR-503 specific to IGF-1 treatment. Similarly, the LIF-treated ESSCs demonstrated specific expression of miR-326, miR-181, and miR-22, as they were nonsignificant in IGF-treated ESSCs. To elucidate the possible downstream pathways, we performed in silico mapping of the said miRNAs into ingenuity pathway analysis. Our findings revealed the important mRNA targets of the miRNAs and suggested specific interactomes. The above studies introduced a new genre of miRNAs for ESSC-based neuroregenerative therapeutic applications.

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation.

PubMed

Ballester-Beltrán, José; Trujillo, Sara; Alakpa, Enateri V; Compañ, Vicente; Gavara, Rafael; Meek, Dominic; West, Christopher C; Péault, Bruno; Dalby, Matthew J; Salmerón-Sánchez, Manuel

2017-08-14

Sandwichlike (SW) cultures are engineered as a multilayer technology to simultaneously stimulate dorsal and ventral cell receptors, seeking to mimic cell adhesion in three-dimensional (3D) environments in a reductionist manner. The effect of this environment on cell differentiation was investigated for several cell types cultured in standard growth media, which promotes proliferation on two-dimensional (2D) surfaces and avoids any preferential differentiation. First, murine C2C12 myoblasts showed specific myogenic differentiation. Human mesenchymal stem cells (hMSCs) of adipose and bone marrow origin, which can differentiate toward a wider variety of lineages, showed again myodifferentiation. Overall, this study shows myogenic differentiation in normal growth media for several cell types under SW conditions, avoiding the use of growth factors and cytokines, i.e., solely by culturing cells within the SW environment. Mechanistically, it provides further insights into the balance between integrin adhesion to the dorsal substrate and the confinement imposed by the SW system.

Nuclear Mechanics and Stem Cell Differentiation.

PubMed

Mao, Xinjian; Gavara, Nuria; Song, Guanbin

2015-12-01

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

Confined Sandwichlike Microenvironments Tune Myogenic Differentiation

PubMed Central

2017-01-01

Sandwichlike (SW) cultures are engineered as a multilayer technology to simultaneously stimulate dorsal and ventral cell receptors, seeking to mimic cell adhesion in three-dimensional (3D) environments in a reductionist manner. The effect of this environment on cell differentiation was investigated for several cell types cultured in standard growth media, which promotes proliferation on two-dimensional (2D) surfaces and avoids any preferential differentiation. First, murine C2C12 myoblasts showed specific myogenic differentiation. Human mesenchymal stem cells (hMSCs) of adipose and bone marrow origin, which can differentiate toward a wider variety of lineages, showed again myodifferentiation. Overall, this study shows myogenic differentiation in normal growth media for several cell types under SW conditions, avoiding the use of growth factors and cytokines, i.e., solely by culturing cells within the SW environment. Mechanistically, it provides further insights into the balance between integrin adhesion to the dorsal substrate and the confinement imposed by the SW system. PMID:28824958

Three Steps Lead to Differentiation

ERIC Educational Resources Information Center

Bowgren, Linda; Sever, Kathryn

2010-01-01

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

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…

Drug Use and Differential Association

ERIC Educational Resources Information Center

Griffin, Brenda S.; Griffin, Charles T.

1978-01-01

Research using the differential association theory has traditionally focused on a broad general conception of delinquent or criminal behavior. This research, however, examines Sutherland's theory as it applies to drug use as a specific delinquency type. Two distinct differential association processes are proposed to explain the genesis of drug…

Direct Validation of Differential Prediction.

ERIC Educational Resources Information Center

Lunneborg, Clifford E.

Using academic achievement data for 655 University students, direct validation of differential predictions based on a battery of aptitude/achievement measures selected for their differential prediction efficiency was attempted. In the cross-validation of the prediction of actual differences among five academic area GPA's, this set of differential…

Stochastic differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sobczyk, K.

1990-01-01

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

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

ERIC Educational Resources Information Center

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

2012-01-01

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

An Optimized and Simplified System of Mouse Embryonic Stem Cell Cardiac Differentiation for the Assessment of Differentiation Modifiers

PubMed Central

Hartman, Matthew E.; Librande, Jason R.; Medvedev, Ivan O.; Ahmad, Rabiah N.; Moussavi-Harami, Farid; Gupta, Pritha P.; Chien, Wei-Ming; Chin, Michael T.

2014-01-01

Generating cardiomyocytes from embryonic stem cells is an important technique for understanding cardiovascular development, the origins of cardiovascular diseases and also for providing potential reagents for cardiac repair. Numerous methods have been published but often are technically challenging, complex, and are not easily adapted to assessment of specific gene contributions to cardiac myocyte differentiation. Here we report the development of an optimized protocol to induce the differentiation of mouse embryonic stem cells to cardiac myocytes that is simplified and easily adapted for genetic studies. Specifically, we made four critical findings that distinguish our protocol: 1) mouse embryonic stem cells cultured in media containing CHIR99021 and PD0325901 to maintain pluripotency will efficiently form embryoid bodies containing precardiac mesoderm when cultured in these factors at a reduced dosage, 2) low serum conditions promote cardiomyocyte differentiation and can be used in place of commercially prepared StemPro nutrient supplement, 3) the Wnt inhibitor Dkk-1 is dispensable for efficient cardiac differentiation and 4) tracking differentiation efficiency may be done with surface expression of PDGFRα alone. In addition, cardiac mesodermal precursors generated by this system can undergo lentiviral infection to manipulate the expression of specific target molecules to assess effects on cardiac myocyte differentiation and maturation. Using this approach, we assessed the effects of CHF1/Hey2 on cardiac myocyte differentiation, using both gain and loss of function. Overexpression of CHF1/Hey2 at the cardiac mesoderm stage had no apparent effect on cardiac differentiation, while knockdown of CHF1/Hey2 resulted in increased expression of atrial natriuretic factor and connexin 43, suggesting an alteration in the phenotype of the cardiomyocytes. In summary we have generated a detailed and simplified protocol for generating cardiomyocytes from mES cells that is

Differentiation: Lessons from Master Teachers

ERIC Educational Resources Information Center

Carolan, Jennifer; Guinn, Abigail

2007-01-01

Carolan and Guinn assert that differentiated instruction helps diversity thrive. Observing how experienced teachers practice differentiation in real-life situations helps teachers who are reluctant to try such strategies take the plunge. The authors draw on two observational studies they conducted of five expert teachers in a high-performing,…

Leadership for Differentiating Schools & Classrooms.

ERIC Educational Resources Information Center

Tomlinson, Carol Ann; Allan, Susan Demirsky

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

Genetics Home Reference: congenital deafness with labyrinthine aplasia, microtia, and microdontia

MedlinePlus

... Tekin M, Hişmi BO, Fitoz S, Ozdağ H, Cengiz FB, Sirmaci A, Aslan I, Inceoğlu B, Yüksel-Konuk ... Tekin M, Oztürkmen Akay H, Fitoz S, Birnbaum S, Cengiz FB, Sennaroğlu L, Incesulu A, Yüksel Konuk EB, Hasanefendioğlu ...

Dynamic Visual Acuity While Walking in Normals and Labyrinthine-Deficient Patients

NASA Technical Reports Server (NTRS)

Hillman, Edward J.; Bloomberg, Jacob J.; McDonald, P. Vernon; Cohen, Helen S.

1996-01-01

We describe a new, objective, easily administered test of dynamic visual acuity (DVA) while walking. Ten normal subjects and five patients with histories of severe bilateral vestibular dysfunctions participated in this study. Subjects viewed a visual display of numerals of different font sizes presented on a laptop computer while they stood still and while they walked on a motorized treadmill. Treadmill speed was adapted for 4 of 5 patients. Subjects were asked to identify the numerals as they appeared on the computer screen. Test results were reasonably repeatable in normals. The percent correct responses at each font size dropped slightly while walking in normals and dropped significantly more in patients. Patients performed significantly worse than normals while standing still and while walking. This task may be useful for evaluating post-flight astronauts and vestibularly impaired patients.

Intestinal development and differentiation

PubMed Central

Noah, Taeko K.; Donahue, Bridgitte; Shroyer, Noah F.

2011-01-01

In this review, we present an overview of intestinal development and cellular differentiation of the intestinal epithelium. The review is separated into two sections: Section one summarizes organogenesis of the small and large intestines, including endoderm and gut tube formation in early embryogenesis, villus morphogenesis, and crypt formation. Section two reviews cell fate specification and differentiation of each cell type within the intestinal epithelium. Growth factor and transcriptional networks that regulate these developmental processes are summarized. PMID:21978911

Research progress on the proliferation and differentiation of

NASA Astrophysics Data System (ADS)

An, A.; Tan, B.

Space environments such as microgravity magnetic field radiation and heavy metal ions affects the development and functions of human and mammalian cells To study these influences and the corresponding metabolisms is in favour of knowing about the development and differentiation process of organism cells In recent years researches on the differentiation of stem cells induced in vitro provide a new pathway for the repair of tissue lesion and therapy of human diseases Stem cells are potential in capable of differentiating into different functional cells But there has no reliable methods to induce the stem cells differentiating forward specific cells and to gain enough cells for transplantation which limited their application on clinical therapy It has been indicated that microgravity influenced embryonic development hematopoietic and mesenchymal stem cells and so on Hematopoietic stem cell migration and its differentiation were affected by microgravity The specific differentiation of hematopoietic stem cells was inhibited under microgravity The expression of proteins regulating cell cycle period also changed Mesenchymal stem cells provide a source of cells for the repair of musculoskeletal tissue in ground experiment While under microgravity the proliferation and differentiation of mesenchymal stem cells were influenced along with the differentiated cells function changed Furthermore in the differentiation process of stem cells under microgravity the mechanism of signal transport was also affected and the specific differentiation

The role of facial canal diameter in the pathogenesis and grade of Bell's palsy: a study by high resolution computed tomography.

PubMed

Celik, Onur; Eskiizmir, Gorkem; Pabuscu, Yuksel; Ulkumen, Burak; Toker, Gokce Tanyeri

The exact etiology of Bell's palsy still remains obscure. The only authenticated finding is inflammation and edema of the facial nerve leading to entrapment inside the facial canal. To identify if there is any relationship between the grade of Bell's palsy and diameter of the facial canal, and also to study any possible anatomic predisposition of facial canal for Bell's palsy including parts which have not been studied before. Medical records and temporal computed tomography scans of 34 patients with Bell's palsy were utilized in this retrospective clinical study. Diameters of both facial canals (affected and unaffected) of each patient were measured at labyrinthine segment, geniculate ganglion, tympanic segment, second genu, mastoid segment and stylomastoid foramen. The House-Brackmann (HB) scale of each patient at presentation and 3 months after the treatment was evaluated from their medical records. The paired samples t-test and Wilcoxon signed-rank test were used for comparison of width between the affected side and unaffected side. The Wilcoxon signed-rank test was also used for evaluation of relationship between the diameter of facial canal and the grade of the Bell's palsy. Significant differences were established at a level of p=0.05 (IBM SPSS Statistics for Windows, Version 21.0.; Armonk, NY, IBM Corp). Thirty-four patients - 16 females, 18 males; mean age±Standard Deviation, 40.3±21.3 - with Bell's palsy were included in the study. According to the HB facial nerve grading system; 8 patients were grade V, 6 were grade IV, 11 were grade III, 8 were grade II and 1 patient was grade I. The mean width at the labyrinthine segment of the facial canal in the affected temporal bone was significantly smaller than the equivalent in the unaffected temporal bone (p=0.00). There was no significant difference between the affected and unaffected temporal bones at the geniculate ganglion (p=0.87), tympanic segment (p=0.66), second genu (p=0.62), mastoid segment (p=0

Operation bandwidth optimization of photonic differentiators.

PubMed

Yan, Siqi; Zhang, Yong; Dong, Jianji; Zheng, Aoling; Liao, Shasha; Zhou, Hailong; Wu, Zhao; Xia, Jinsong; Zhang, Xinliang

2015-07-27

We theoretically investigate the operation bandwidth limitation of the photonic differentiator including the upper limitation, which is restrained by the device operation bandwidth and the lower limitation, which is restrained by the energy efficiency (EE) and detecting noise level. Taking the silicon photonic crystal L3 nano-cavity (PCN) as an example, for the first time, we experimentally demonstrate that the lower limitation of the operation bandwidth does exist and differentiators with different bandwidths have significantly different acceptable pulse width range of input signals, which are consistent to the theoretical prediction. Furthermore, we put forward a novel photonic differentiator scheme employing cascaded PCNs with different Q factors, which is likely to expand the operation bandwidth range of photonic differentiator dramatically.

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…

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…

Helicopter flight test demonstration of differential GPS

NASA Technical Reports Server (NTRS)

Denaro, R. P.; Beser, J.

1985-01-01

An off-line post-mission processing facility is being established by NASA Ames Research Center to analyze differential GPS flight tests. The current and future differential systems are described, comprising an airborne segment in an SH-3 helicopter, a GPS ground reference station, and a tracking system. The post-mission processing system provides for extensive measurement analysis and differential computation. Both differential range residual corrections and navigation corrections are possible. Some preliminary flight tests were conducted in a landing approach scenario and statically. Initial findings indicate the possible need for filter matching between airborne and ground systems (if used in a navigation correction technique), the advisability of correction smoothing before airborne incorporation, and the insensitivity of accuracy to either of the differential techniques or to update rates.

Troglitazone induces differentiation in Trypanosoma brucei

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denninger, Viola; Figarella, Katherine; Schoenfeld, Caroline

2007-05-15

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

Differential roles of vascular endothelial growth factor receptors 1 and 2 in dendritic cell differentiation.

PubMed

Dikov, Mikhail M; Ohm, Joyce E; Ray, Neelanjan; Tchekneva, Elena E; Burlison, Jared; Moghanaki, Drew; Nadaf, Sorena; Carbone, David P

2005-01-01

Impaired Ag-presenting function in dendritic cells (DCs) due to abnormal differentiation is an important mechanism of tumor escape from immune control. A major role for vascular endothelial growth factor (VEGF) and its receptors, VEGFR1/Flt-1 and VEGFR2/KDR/Flk-1, has been documented in hemopoietic development. To study the roles of each of these receptors in DC differentiation, we used an in vitro system of myeloid DC differentiation from murine embryonic stem cells. Exposure of wild-type, VEGFR1(-/-), or VEGFR2(-/-) embryonic stem cells to exogenous VEGF or the VEGFR1-specific ligand, placental growth factor, revealed distinct roles of VEGF receptors. VEGFR1 is the primary mediator of the VEGF inhibition of DC maturation, whereas VEGFR2 tyrosine kinase signaling is essential for early hemopoietic differentiation, but only marginally affects final DC maturation. SU5416, a VEGF receptor tyrosine kinase inhibitor, only partially rescued the mature DC phenotype in the presence of VEGF, suggesting the involvement of both tyrosine kinase-dependent and independent inhibitory mechanisms. VEGFR1 signaling was sufficient for blocking NF-kappaB activation in bone marrow hemopoietic progenitor cells. VEGF and placental growth factor affect the early stages of myeloid/DC differentiation. The data suggest that therapeutic strategies attempting to reverse the immunosuppressive effects of VEGF in cancer patients might be more effective if they specifically targeted VEGFR1.

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.

Constant-Differential-Pressure Two-Fluid Accumulator

NASA Technical Reports Server (NTRS)

Piecuch, Benjamin; Dalton, Luke T.

2010-01-01

A two-fluid accumulator has been designed, built, and demonstrated to provide an acceptably close approximation to constant differential static pressure between two fluids over the full ranges of (1) accumulator stroke, (2) rates of flow of the fluids, and (3) common static pressure applied to the fluids. Prior differential- pressure two-fluid accumulators are generally not capable of maintaining acceptably close approximations to constant differential pressures. The inadequacies of a typical prior differential-pressure two-fluid accumulator can be summarized as follows: The static differential pressure is governed by the intrinsic spring rate (essentially, the stiffness) of an accumulator tank. The spring rate can be tailored through selection of the tank-wall thickness, selection of the number and/or shape of accumulator convolutions, and/or selection of accumulator material(s). Reliance on the intrinsic spring rate of the tank results in three severe limitations: (1) The spring rate and the expulsion efficiency tend to be inversely proportional to each other: that is to say, as the stiffness (and thus the differential pressure) is increased, the range of motion of the accumulator is reduced. (2) As the applied common static pressure increases, the differential pressure tends to decrease. An additional disadvantage, which may or may not be considered limiting, depending on the specific application, is that an increase in stiffness entails an increase in weight. (3) The additional weight required by a low expulsion efficiency accumulator eliminates the advantage given to such gas storage systems. The high expulsion efficiency provided by this two-fluid accumulator allows for a lightweight, tightly packaged system, which can be used in conjunction with a fuel cell-based system.

Rethinking Differentiation--Using Teachers' Time Most Effectively

ERIC Educational Resources Information Center

Marshall, Kim

2016-01-01

The goals of differentiation are laudable, but in recent years, many question whether it is really possible for a teacher to tailor instruction for 20 to 30 different students and whether it's desirable to differentiate by learning styles. Differentiation is just one factor in effective instruction. Supervisors who walk into a classroom looking…

The differential effects of 2% oxygen preconditioning on the subsequent differentiation of mouse and human pluripotent stem cells.

PubMed

Fynes, Kate; Tostoes, Rui; Ruban, Ludmila; Weil, Ben; Mason, Christopher; Veraitch, Farlan S

2014-08-15

A major challenge facing the development of effective cell therapies is the efficient differentiation of pluripotent stem cells (PSCs) into pure populations. Lowering oxygen tension to physiological levels can affect both the expansion and differentiation stages. However, to date, there are no studies investigating the knock-on effect of culturing PSCs under low oxygen conditions on subsequent lineage commitment at ambient oxygen levels. PSCs were passaged three times at 2% O2 before allowing cells to spontaneously differentiate as embryoid bodies (EBs) in high oxygen (20% O2) conditions. Maintenance of mouse PSCs in low oxygen was associated with a significant increase in the expression of early differentiation markers FGF5 and Eomes, while conversely we observed decreased expression of these genes in human PSCs. Low oxygen preconditioning primed mouse PSCs for their subsequent differentiation into mesodermal and endodermal lineages, as confirmed by increased gene expression of Eomes, Goosecoid, Brachyury, AFP, Sox17, FoxA2, and protein expression of Brachyury, Eomes, Sox17, FoxA2, relative to high oxygen cultures. The effects extended to the subsequent formation of more mature mesodermal lineages. We observed significant upregulation of cardiomyocyte marker Nkx2.5, and critically a decrease in the number of contaminant pluripotent cells after 12 days using a directed cardiomyocyte protocol. However, the impact of low oxygen preconditioning was to prime human cells for ectodermal lineage commitment during subsequent EB differentiation, with significant upregulation of Nestin and β3-tubulin. Our research demonstrates the importance of oxygen tension control during cell maintenance on the subsequent differentiation of both mouse and human PSCs, and highlights the differential effects.

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.

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.

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

PubMed

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

2015-06-01

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

Higher-order automatic differentiation of mathematical functions

NASA Astrophysics Data System (ADS)

Charpentier, Isabelle; Dal Cappello, Claude

2015-04-01

Functions of mathematical physics such as the Bessel functions, the Chebyshev polynomials, the Gauss hypergeometric function and so forth, have practical applications in many scientific domains. On the one hand, differentiation formulas provided in reference books apply to real or complex variables. These do not account for the chain rule. On the other hand, based on the chain rule, the automatic differentiation has become a natural tool in numerical modeling. Nevertheless automatic differentiation tools do not deal with the numerous mathematical functions. This paper describes formulas and provides codes for the higher-order automatic differentiation of mathematical functions. The first method is based on Faà di Bruno's formula that generalizes the chain rule. The second one makes use of the second order differential equation they satisfy. Both methods are exemplified with the aforementioned functions.

Dichotomies for generalized ordinary differential equations and applications

NASA Astrophysics Data System (ADS)

Bonotto, E. M.; Federson, M.; Santos, F. L.

2018-03-01

In this work we establish the theory of dichotomies for generalized ordinary differential equations, introducing the concepts of dichotomies for these equations, investigating their properties and proposing new results. We establish conditions for the existence of exponential dichotomies and bounded solutions. Using the correspondences between generalized ordinary differential equations and other equations, we translate our results to measure differential equations and impulsive differential equations. The fact that we work in the framework of generalized ordinary differential equations allows us to manage functions with many discontinuities and of unbounded variation.

Differential Activity-Driven Instabilities in Biphasic Active Matter

NASA Astrophysics Data System (ADS)

Weber, Christoph A.; Rycroft, Chris H.; Mahadevan, L.

2018-06-01

Active stresses can cause instabilities in contractile gels and living tissues. Here we provide a generic hydrodynamic theory that treats these systems as a mixture of two phases of varying activity and different mechanical properties. We find that differential activity between the phases causes a uniform mixture to undergo a demixing instability. We follow the nonlinear evolution of the instability and characterize a phase diagram of the resulting patterns. Our study complements other instability mechanisms in mixtures driven by differential adhesion, differential diffusion, differential growth, and differential motion.

PPARγ ligand production is tightly linked to clonal expansion during initiation of adipocyte differentiation[S

PubMed Central

Hallenborg, Philip; Petersen, Rasmus Koefoed; Feddersen, Søren; Sundekilde, Ulrik; Hansen, Jacob B.; Blagoev, Blagoy; Madsen, Lise; Kristiansen, Karsten

2014-01-01

Adipocyte differentiation is orchestrated by the ligand-activated nuclear receptor PPARγ. Endogenous ligands comprise oxidized derivatives of arachidonic acid and structurally similar PUFAs. Although expression of PPARγ peaks in mature adipocytes, ligands are produced primarily at the onset of differentiation. Concomitant with agonist production, murine fibroblasts undergo two rounds of mitosis referred to as mitotic clonal expansion. Here we show that mouse embryonic fibroblasts deficient in either of two cell cycle inhibitors, the transcription factor p53 or its target gene encoding the cyclin-dependent kinase inhibitor p21, exhibit increased adipogenic potential. The antiadipogenic effect of p53 relied on its transcriptional activity and p21 expression but was circumvented by administration of an exogenous PPARγ agonist suggesting a linkage between cell cycling and PPARγ ligand production. Indeed, cell cycle inhibitory compounds decreased PPARγ ligand production in differentiating 3T3-L1 preadipocytes. Furthermore, these inhibitors abolished the release of arachidonic acid induced by the hormonal cocktail initiating adipogenesis. Collectively, our results suggest that murine fibroblasts require clonal expansion for PPARγ ligand production at the onset of adipocyte differentiation. PMID:25312885

Differential Calculus on h-Deformed Spaces

NASA Astrophysics Data System (ADS)

Herlemont, Basile; Ogievetsky, Oleg

2017-10-01

We construct the rings of generalized differential operators on the h-deformed vector space of gl-type. In contrast to the q-deformed vector space, where the ring of differential operators is unique up to an isomorphism, the general ring of h-deformed differential operators {Diff}_{h},σ(n) is labeled by a rational function σ in n variables, satisfying an over-determined system of finite-difference equations. We obtain the general solution of the system and describe some properties of the rings {Diff}_{h},σ(n).

Calculated differential and double differential cross section of DT neutron induced reactions on natural chromium (Cr)

NASA Astrophysics Data System (ADS)

Rajput, Mayank; Vala, Sudhirsinh; Srinivasan, R.; Abhangi, M.; Subhash, P. V.; Pandey, B.; Rao, C. V. S.; Bora, D.

2018-01-01

Chromium is an important alloying element of stainless steel (SS) and SS is the main constituent of structural material proposed for fusion reactors. Energy and double differential cross section data will be required to estimate nuclear responses in the materials used in fusion reactors. There are no experimental data of energy and double differential cross section, available for neutron induced reactions on natural chromium at 14 MeV neutron energy. In this study, energy and double differential cross section data of (n,p) and (n,α) reactions for all the stable isotopes of chromium have been estimated, using appropriate nuclear models in TALYS code. The cross section data of stable isotopes are later converted into the energy and double differential cross section data of natural Cr using the isotopic abundance. The contribution from compound, pre-equilibrium and direct nuclear reaction to total reaction have also been calculated for 52,50Cr(n,p) and 52Cr(n,α). The calculation of energy differential cross section shows that most of emitted protons and alpha particles are of 3 and 8 MeV respectively. The calculated data is compared with the data from EXFOR data library and is found to be in good agreement.

Vertical structures in vibrated wormlike micellar solutions

NASA Astrophysics Data System (ADS)

Epstein, Tamir; Deegan, Robert

2008-11-01

Vertically vibrated shear thickening particulate suspensions can support a free-standing interfaces oriented parallel to gravity. We find that shear thickening worm-like micellar solutions also support such vertical interfaces. Above a threshold in acceleration, the solution spontaneously accumulates into a labyrinthine pattern characterized by a well-defined vertical edge. The formation of vertical structures is of interest because they are unique to shear-thickening fluids, and they indicate the existence of an unknown stress bearing mechanism.

Heterogeneity of proangiogenic features in mesenchymal stem cells derived from bone marrow, adipose tissue, umbilical cord, and placenta.

PubMed

Du, Wen Jing; Chi, Ying; Yang, Zhou Xin; Li, Zong Jin; Cui, Jun Jie; Song, Bao Quan; Li, Xue; Yang, Shao Guang; Han, Zhi Bo; Han, Zhong Chao

2016-11-10

Mesenchymal stem cells (MSCs) have been widely proven effective for therapeutic angiogenesis in ischemia animal models as well as clinical vascular diseases. Because of the invasive method, limited resources, and aging problems of adult tissue-derived MSCs, more perinatal tissue-derived MSCs have been isolated and studied as promising substitutable MSCs for cell transplantation. However, fewer studies have comparatively studied the angiogenic efficacy of MSCs derived from different tissues sources. Here, we evaluated whether the in-situ environment would affect the angiogenic potential of MSCs. We harvested MSCs from adult bone marrow (BMSCs), adipose tissue (AMSCs), perinatal umbilical cord (UMSCs), and placental chorionic villi (PMSCs), and studied their "MSC identity" by flow cytometry and in-vitro trilineage differentiation assay. Then we comparatively studied their endothelial differentiation capabilities and paracrine actions side by side in vitro. Our data showed that UMSCs and PMSCs fitted well with the minimum standard of MSCs as well as BMSCs and AMSCs. Interestingly, we found that MSCs regardless of their tissue origins could develop similar endothelial-relevant functions in vitro, including producing eNOS and uptaking ac-LDL during endothelial differentiation in spite of their feeble expression of endothelial-related genes and proteins. Additionally, we surprisingly found that BMSCs and PMSCs could directly form tubular structures in vitro on Matrigel and their conditioned medium showed significant proangiogenic bioactivities on endothelial cells in vitro compared with those of AMSCs and UMSCs. Besides, several angiogenic genes were upregulated in BMSCs and PMSCs in comparison with AMSCs and UMSCs. Moreover, enzyme-linked immunosorbent assay further confirmed that BMSCs secreted much more VEGF, and PMSCs secreted much more HGF and PGE2. Our study demonstrated the heterogeneous proangiogenic properties of MSCs derived from different tissue origins, and

Peptidegic stimulation of differentiation of pineal immune cells.

PubMed

Linkova, N S; Khavinson, V Kh; Chalisova, N I; Katanugina, A S; Koncevaya, E A

2011-11-01

We studied cell composition of the pineal lymphoid tissue and the effect of peptides on its differentiation and proliferation capacity. It was shown that the lymphoid component of the pineal gland in organotypic culture is primarily presented by low-differentiated CD5(+)-lymphocytes, while mature T and B cells are less abundant. Dipeptide vilon stimulates differentiation of precursors into T-helpers, cytotoxic T lymphocytes, and B cells, while tetrapeptide epithalon stimulated their differentiation towards B cells. Tripeptide vesugen had no effect on differentiation capacity of immune cells of the pineal gland, but enhanced their proliferation potential. Thus, dipeptide vilon acts as an inductor of differentiation of pineal immune cells, which can play an important compensatory role in age-related atrophy of the thymus, the central organ of the immune system.

Document Set Differentiability Analyzer v. 0.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Osborn, Thor D.

Software is a JMP Scripting Language (JSL) script designed to evaluate the differentiability of a set of documents that exhibit some conceptual commonalities but are expected to describe substantially different – thus differentiable – categories. The script imports the document set, a subset of which may be partitioned into an additions pool. The bulk of the documents form a basis pool. Text analysis is applied to the basis pool to extract a mathematical representation of its conceptual content, referred to as the document concept space. A bootstrapping approach is applied to that mathematical representation in order to generate a representationmore » of a large population of randomly designed documents that could be written within the concept space, notably without actually writing the text of those documents.The Kolmogorov-Smirnov test is applied to determine whether the basis pool document set exhibits superior differentiation relative to the randomly designed virtual documents produced by bootstrapping. If an additions pool exists, the documents are incrementally added to the basis pool, choosing the best differentiated remaining document at each step. In this manner the impact of additional categories to overall document set differentiability may be assessed.The software was developed to assess the differentiability of job description document sets. Differentiability is key to meaningful categorization. Poor job differentiation may have economic, ethical, and/or legal implications for an organization. Job categories are used in the assignment of market-based salaries; consequently, poor differentiation of job duties may set the stage for legal challenges if very similar jobs pay differently depending on title, a circumstance that also invites economic waste.The software can be applied to ensure job description set differentiability, reducing legal, economic, and ethical risks to an organization and its people. The extraction of the conceptual space to a

Ferroelectric Field-Effect Transistor Differential Amplifier Circuit Analysis

NASA Technical Reports Server (NTRS)

Phillips, Thomas A.; MacLeod, Todd C.; Ho, Fat D.

2008-01-01

There has been considerable research investigating the Ferroelectric Field-Effect Transistor (FeFET) in memory circuits. However, very little research has been performed in applying the FeFET to analog circuits. This paper investigates the use of FeFETs in a common analog circuit, the differential amplifier. The two input Metal-Oxide-Semiconductor (MOS) transistors in a general MOS differential amplifier circuit are replaced with FeFETs. Resistors are used in place of the other three MOS transistors. The FeFET model used in the analysis has been previously reported and was based on experimental device data. Because of the FeFET hysteresis, the FeFET differential amplifier has four different operating modes depending on whether the FeFETs are positively or negatively polarized. The FeFET differential amplifier operation in the different modes was analyzed by calculating the amplifier voltage transfer and gain characteristics shown in figures 2 through 5. Comparisons were made between the FeFET differential amplifier and the standard MOS differential amplifier. Possible applications and benefits of the FeFET differential amplifier are discussed.

Differentially Private Distributed Sensing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fink, Glenn A.

The growth of the Internet of Things (IoT) creates the possibility of decentralized systems of sensing and actuation, potentially on a global scale. IoT devices connected to cloud networks can offer Sensing and Actuation as a Service (SAaaS) enabling networks of sensors to grow to a global scale. But extremely large sensor networks can violate privacy, especially in the case where IoT devices are mobile and connected directly to the behaviors of people. The thesis of this paper is that by adapting differential privacy (adding statistically appropriate noise to query results) to groups of geographically distributed sensors privacy could bemore » maintained without ever sending all values up to a central curator and without compromising the overall accuracy of the data collected. This paper outlines such a scheme and performs an analysis of differential privacy techniques adapted to edge computing in a simulated sensor network where ground truth is known. The positive and negative outcomes of employing differential privacy in distributed networks of devices are discussed and a brief research agenda is presented.« less

Building Measures of Instructional Differentiation from Teacher Checklists

ERIC Educational Resources Information Center

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

2012-01-01

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

Angiopoietin-Like 4 Regulates Epidermal Differentiation

PubMed Central

Huang, Royston-Luke; Goh, Yan Yih; Wang, Xiao Ling; Tang, Mark Boon Yang; Tan, Nguan Soon

2011-01-01

The nuclear hormone receptor PPARβ/δ is integral to efficient wound re-epithelialization and implicated in epidermal maturation. However, the mechanism underlying the latter process of epidermal differentiation remains unclear. We showed that ligand-activated PPARβ/δ indirectly stimulated keratinocyte differentiation, requiring de novo gene transcription and protein translation. Using organotypic skin cultures constructed from PPARβ/δ- and angiopoietin-like 4 (ANGPTL4)-knockdown human keratinocytes, we showed that the expression of ANGPTL4, a PPARβ/δ target gene, is essential for the receptor mediated epidermal differentiation. The pro-differentiation effect of PPARβ/δ agonist GW501516 was also abolished when keratinocytes were co-treated with PPARβ/δ antagonist GSK0660 and similarly in organotypic skin culture incubated with blocking ANGPTL4 monoclonal antibody targeted against the C-terminal fibrinogen-like domain. Our focused real-time PCR gene expression analysis comparing the skin biopsies from wildtype and ANGPTL4-knockout mice confirmed a consistent down-regulation of numerous genes involved in epidermal differentiation and proliferation in the ANGPTL4-knockout skin. We further showed that the deficiency of ANGPTL4 in human keratinocytes and mice skin have diminished expression of various protein kinase C isotypes and phosphorylated transcriptional factor activator protein-1, which are well-established for their roles in keratinocyte differentiation. Chromatin immunoprecipitation confirmed that ANGPTL4 stimulated the activation and binding of JUNB and c-JUN to the promoter region of human involucrin and transglutaminase type 1 genes, respectively. Taken together, we showed that PPARβ/δ regulates epidermal maturation via ANGPTL4-mediated signalling pathway. PMID:21966511

Myb permits multilineage airway epithelial cell differentiation

PubMed Central

Pan, Jie-hong; Adair-Kirk, Tracy L.; Patel, Anand C.; Huang, Tao; Yozamp, Nicholas S.; Xu, Jian; Reddy, E. Premkumar; Byers, Derek E.; Pierce, Richard A.; Holtzman, Michael J.; Brody, Steven L.

2014-01-01

The epithelium of the pulmonary airway is specially differentiated to provide defense against environmental insults, but also subject to dysregulated differentiation that results in lung disease. The current paradigm for airway epithelial differentiation is a one-step program whereby a p63+ basal epithelial progenitor cell generates a ciliated or secretory cell lineage, but the cue for this transition and whether there are intermediate steps is poorly defined. Here we identify transcription factor Myb as a key regulator that permits early multilineage differentiation of airway epithelial cells. Myb+ cells were identified as p63− and therefore distinct from basal progenitor cells, but were still negative for markers of differentiation. Myb RNAi treatment of primary-culture airway epithelial cells and Myb gene deletion in mice resulted in a p63− population with failed maturation of Foxj1+ ciliated cells, as well as Scbg1a1+ and Muc5ac+ secretory cells. Consistent with these findings, analysis of whole genome expression of Myb-deficient cells identified Myb-dependent programs for ciliated and secretory cell differentiation. Myb+ cells were rare in human airways but were increased in regions of ciliated cells and mucous cell hyperplasia in samples from subjects with chronic obstructive pulmonary disease. Together, the results show that a p63− Myb+ population of airway epithelial cells represents a distinct intermediate stage of differentiation that is required under normal conditions and may be heightened in airway disease. PMID:25103188

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.

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…

Differential effects of the extracellular microenvironment on human embryonic stem cell differentiation into keratinocytes and their subsequent replicative life span.

PubMed

Movahednia, Mohammad Mehdi; Kidwai, Fahad Karim; Zou, Yu; Tong, Huei Jinn; Liu, Xiaochen; Islam, Intekhab; Toh, Wei Seong; Raghunath, Michael; Cao, Tong

2015-04-01

Culture microenvironment plays a critical role in the propagation and differentiation of human embryonic stem cells (hESCs) and their differentiated progenies. Although high efficiency of hESC differentiation to keratinocytes (hESC-Kert) has been achieved, little is known regarding the effects of early culture microenvironment and pertinent extracellular matrix (ECM) interactions during epidermal commitment on subsequent proliferative capacity of hESC-Kert. The aim of this study is to evaluate the effects of the different ECM microenvironments during hESC differentiation on subsequent replicative life span of hESC-Kert. In doing so, H1-hESCs were differentiated to keratinocytes (H1-Kert) in two differentiation systems. The first system employed autologous fibroblast feeder support, in which keratinocytes (H1-Kert(ACC)) were derived by coculture of hESCs with hESC-derived fibroblasts (H1-ebFs). The second system employed a novel decellularized matrix from H1-ebFs to create a dermoepidermal junction-like (DEJ) matrix. H1-Kert(AFF) were derived by differentiation of hESCs on the feeder-free system employing the DEJ matrix. Our study indicated that the feeder-free system with the use of DEJ matrix was more efficient in differentiation of hESCs toward epidermal progenitors. However, the feeder-free system was not sufficient to support the subsequent replicative capacity of differentiated keratinocytes. Of note, H1-Kert(AFF) showed limited replicative capacity with reduced telomere length and early cellular senescence. We further showed that the lack of cell-cell interactions during epidermal commitment led to heightened production of TGF-β1 by hESC-Kert during extended culture, which in turn was responsible for resulting in the limited replicative life span with cellular senescence of hESC-Kert derived under the feeder-free culture system. This study highlights for the first time the importance of the culture microenvironment and cell-ECM interactions during

Optical spatial differentiator based on subwavelength high-contrast gratings

NASA Astrophysics Data System (ADS)

Dong, Zhewei; Si, Jiangnan; Yu, Xuanyi; Deng, Xiaoxu

2018-04-01

An optical spatial differentiator based on subwavelength high-contrast gratings (HCGs) is proposed experimentally. The spatial differentiation property of the subwavelength HCG is analyzed by calculating its spatial spectral transfer function based on the periodic waveguide theory. By employing the FDTD solutions, the performance of the subwavelength HCG spatial differentiator was investigated numerically. The subwavelength HCG differentiator with the thickness at the nanoscale was fabricated on the quartz substrate by electron beam lithography and Bosch deep silicon etching. Observed under an optical microscope with a CCD camera, the spatial differentiation of the incident field profile was obtained by the subwavelength HCG differentiator in transmission without Fourier lens. By projecting the images of slits, letter "X," and a cross on the subwavelength HCG differentiator, edge detections of images were obtained in transmission. With the nanoscale HCG structure and simple optical implementation, the proposed optical spatial differentiator provides the prospects for applications in optical computing systems and parallel data processing.

Modular Expression Language for Ordinary Differential Equation Editing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Blake, Robert C.

MELODEEis a system for describing systems of initial value problem ordinary differential equations, and a compiler for the language that produces optimized code to integrate the differential equations. Features include rational polynomial approximation for expensive functions and automatic differentiation for symbolic jacobians

Microcystic adnexal carcinoma with sebaceous differentiation: Three cases.

PubMed

Fernandez-Flores, Angel; Llamas-Velasco, Mar; Saus, Carles; Patel, Anisha; Rutten, Arno

2018-04-01

Microcystic adnexal carcinoma (MAC) is a low-grade malignant tumor of the skin. Histologically, this tumor shows a biphasic pattern, with cords and nests of basaloid cells, as well as keratin horn cysts. This biphasic histological appearance has been interpreted by some authors as a sign of double eccrine and folliculosebaceous-apocrine differentiation, whereas some other authors defend a solely eccrine differentiation. In this context, sebaceous differentiation in MAC would support the first option. However, there are only 3 cases of MAC with sebaceous differentiation in the literature, and all of them were reported before adipophilin was available, which in the appropriate context (eg, testing clear cells for sebaceous vs eccrine differentiation) is very useful. In this study, we present 3 cases of MAC with focal sebaceous differentiation confirmed by immunoexpression of adipophilin in the sebaceous foci. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Alpha-adrenergic blocker mediated osteoblastic stem cell differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Choi, Yoon Jung; Lee, Jue Yeon; Research Center, Nano Intelligent Biomedical Engineering Corporation

Highlights: Black-Right-Pointing-Pointer Doxazocin directly up-regulated bone metabolism at a low dose. Black-Right-Pointing-Pointer Doxazocin induced osteoblastic stem cell differentiation without affecting cell proliferation. Black-Right-Pointing-Pointer This osteogenic stem cell differentiation is mediated by ERK-signal dependent pathway. -- Abstract: Recent researches have indicated a role for antihypertensive drugs including alpha- or beta-blockers in the prevention of bone loss. Some epidemiological studies reported the protective effects of those agents on fracture risk. However, there is limited information on the association with those agents especially at the mechanism of action. In the present study, we investigated the effects of doxazosin, an alpha-blocker that is clinicallymore » used for the treatment of benign prostatic hyperplasia (BPH) along with antihypertensive medication, on the osteogenic stem cell differentiation. We found that doxazosin increased osteogenic differentiation of human mesenchymal stem cells, detected by Alizarin red S staining and calcein. Doxazosin not only induced expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin, it also resulted in increased phosphorylation of extracellular signal-regulated kinase (ERK1/2), a MAP kinase involved in osteoblastic differentiation. Treatment with U0126, a MAP kinase inhibitor, significantly blocked doxazosin-induced osteoblastic differentiation. Unrelated to activation of osteogenic differentiation by doxazosin, we found that there were no significant changes in adipogenic differentiation or in the expression of adipose-specific genes, including peroxisome proliferator-activated receptor {gamma}, aP2, or LPL. In this report, we suggest that doxazosin has the ability to increase osteogenic cell differentiation via ERK1/2 activation in osteogenic differentiation of adult stem cells, which supports the protective effects of antihypertensive drug on fracture risk

The Human Semicircular Canals Orientation Is More Similar to the Bonobos than to the Chimpanzees

PubMed Central

El Khoury, Marwan; Braga, José; Dumoncel, Jean; Nancy, Javotte; Esclassan, Remi; Vaysse, Frederic

2014-01-01

For some traits, the human genome is more closely related to either the bonobo or the chimpanzee genome than they are to each other. Therefore, it becomes crucial to understand whether and how morphostructural differences between humans, chimpanzees and bonobos reflect the well known phylogeny. Here we comparatively investigated intra and extra labyrinthine semicircular canals orientation using 260 computed tomography scans of extant humans (Homo sapiens), bonobos (Pan paniscus) and chimpanzees (Pan troglodytes). Humans and bonobos proved more similarities between themselves than with chimpanzees. This finding did not fit with the well established chimpanzee – bonobo monophyly. One hypothesis was convergent evolution in which bonobos and humans produce independently similar phenotypes possibly in response to similar selective pressures that may be associated with postural adaptations. Another possibility was convergence following a “random walk” (Brownian motion) evolutionary model. A more parsimonious explanation was that the bonobo-human labyrinthine shared morphology more closely retained the ancestral condition with chimpanzees being subsequently derived. Finally, these results might be a consequence of genetic diversity and incomplete lineage sorting. The remarkable symmetry of the Semicircular Canals was the second major finding of this article with possible applications in taphonomy. It has the potential to investigate altered fossils, inferring the probability of post-mortem deformation which can lead to difficulties in understanding taxonomic variation, phylogenetic relationships, and functional morphology. PMID:24710502

Functional organization of primate translational vestibulo-ocular reflexes and effects of unilateral labyrinthectomy

NASA Technical Reports Server (NTRS)

Angelaki, D. E.; McHenry, M. Q.; Newlands, S. D.; Dickman, J. D.

1999-01-01

Translational vestibulo-ocular reflexes (trVORs) are characterized by distinct spatio-temporal properties and sensitivities that are proportional to the inverse of viewing distance. Anodal (inhibitory) labyrinthine stimulation (100 microA, < 2 s) during motion decreased the high-pass filtered dynamics, as well as horizontal trVOR sensitivity and its dependence on viewing distance. Cathodal (excitatory) currents had opposite effects. Translational VORs were also affected after unilateral labyrinthectomy. Animals lost their ability to modulate trVOR sensitivity as a function of viewing distance acutely after the lesion. These deficits partially recovered over time, albeit a significant reduction in trVOR sensitivity as a function of viewing distance remained in compensated animals. During fore-aft motion, the effects of unilateral labyrinthectomy were more dramatic. Both acute and compensated animals permanently lost their ability to modulate fore-aft trVOR responses as a function of target eccentricity. These results suggest that (1) the dynamics and viewing distance-dependent properties of the trVORs are very sensitive to changes in the resting firing rate of vestibular afferents and, consequently, vestibular nuclei neurons; (2) the most irregularly firing primary otolith afferents that are most sensitive to labyrinthine electrical stimulation might contribute to reflex dynamics and sensitivity; (3) inputs from both labyrinths are necessary for the generation of the translational VORs.

Platelet lysate enhances synovial fluid multipotential stromal cells functions: Implications for therapeutic use.

PubMed

Altaie, Ala; Baboolal, Thomas G; Wall, Owen; Jones, Elena; McGonagle, Dennis

2018-03-01

Although intra-articular injection of platelet products is increasingly used for joint regenerative approaches, there are few data on their biological effects on joint-resident multipotential stromal cells (MSCs), which are directly exposed to the effects of these therapeutic strategies. Therefore, this study investigated the effect of platelet lysate (PL) on synovial fluid-derived MSCs (SF-MSCs), which in vivo have direct access to sites of cartilage injury. SF-MSCs were obtained during knee arthroscopic procedures (N = 7). Colony forming unit-fibroblast (CFU-F), flow-cytometric phenotyping, carboxyfluorescein succinimidyl ester-based immunomodulation for T-cell and trilineage differentiation assays were performed using PL and compared with standard conditions. PL-enhanced SF-MSC (PL-MSC) proliferation as CFU-F colonies was 1.4-fold larger, and growing cultures had shorter population-doubling times. PL-MSCs and fetal calf serum (FCS)-MSCs had the same immunophenotype and similar immunomodulation activities. In chondrogenic and osteogenic differentiation assays, PL-MSCs produced 10% more sulfated-glycosaminoglycan (sGAG) and 45% less Ca ++ compared with FCS-MSCs, respectively. Replacing chondrogenic medium transforming growth factor-β3 with 20% or 50% PL further increased sGAG production of PL-MSCs by 69% and 95%, respectively, compared with complete chondrogenic medium. Also, Dulbecco's Modified Eagle's Medium high glucose (HG-DMEM) plus 50% PL induced more chondrogenesis compared with HG-DMEM plus 10% FCS and was comparable to complete chondrogenic medium. This is the first study to assess SF-MSC responses to PL and provides biological support to the hypothesis that PL may be capable of modulating multiple functional aspects of joint resident MSCs with direct access to injured cartilage. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Analysis of Differentially Expressed Genes Associated with Coronatine-Induced Laticifer Differentiation in the Rubber Tree by Subtractive Hybridization Suppression

PubMed Central

Zhang, Shi-Xin; Wu, Shao-Hua; Chen, Yue-Yi; Tian, Wei-Min

2015-01-01

The secondary laticifer in the secondary phloem is differentiated from the vascular cambia of the rubber tree (Hevea brasiliensis Muell. Arg.). The number of secondary laticifers is closely related to the rubber yield potential of Hevea. Pharmacological data show that jasmonic acid and its precursor linolenic acid are effective in inducing secondary laticifer differentiation in epicormic shoots of the rubber tree. In the present study, an experimental system of coronatine-induced laticifer differentiation was developed to perform SSH identification of genes with differential expression. A total of 528 positive clones were obtained by blue-white screening, of which 248 clones came from the forward SSH library while 280 clones came from the reverse SSH library. Approximately 215 of the 248 clones and 171 of the 280 clones contained cDNA inserts by colony PCR screening. A total of 286 of the 386 ESTs were detected to be differentially expressed by reverse northern blot and sequenced. Approximately 147 unigenes with an average length of 497 bp from the forward and 109 unigenes with an average length of 514 bp from the reverse SSH libraries were assembled and annotated. The unigenes were associated with the stress/defense response, plant hormone signal transduction and structure development. It is suggested that Ca2+ signal transduction and redox seem to be involved in differentiation, while PGA and EIF are associated with the division of cambium initials for COR-induced secondary laticifer differentiation in the rubber tree. PMID:26147807

Productive Struggle for All: Differentiated Instruction

ERIC Educational Resources Information Center

Lynch, Sararose D.; Hunt, Jessica H.; Lewis, Katherine E.

2018-01-01

This article demonstrates how to consider differentiating instruction for diverse learners while maintaining the cognitive demand of a mathematics task. The authors present scenarios involving hypothetical cases of students in inclusive classrooms who engaged in productive struggle within the differentiated task. The authors specifically focus on…

Solving Differential Equations in R: Package deSolve

EPA Science Inventory

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

Differentiating Science Instruction: Secondary science teachers' practices

NASA Astrophysics Data System (ADS)

Maeng, Jennifer L.; Bell, Randy L.

2015-09-01

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

Molecular basis of differentiation therapy for soft tissue sarcomas

PubMed Central

Luther, Gaurav; Rames, Richard; Wagner, Eric R.; Zhu, Gaohui; Luo, Qing; Bi, Yang; Kim, Stephanie H.; Gao, Jian-Li; Huang, Enyi; Yang, Ke; Wang, Linyuan; Liu, Xing; Li, Mi; Hu, Ning; Su, Yuxi; Luo, Xiaoji; Chen, Liang; Luo, Jinyong; Haydon, Rex C.; Luu, Hue H.; Zhou, Lan; He, Tong-Chuan

2015-01-01

Stem cells are undifferentiated precursor cells with the capacity for proliferation or terminal differentiation. Progression down the differentiation cascade results in a loss of proliferative potential in exchange for the differentiated phenotype. This balance is tightly regulated in the physiologic state. Recent studies, however, have demonstrated that during tumorigenesis, disruptions preventing terminal differentiation allow cancer cells to maintain a proliferative, precursor cell phenotype. Current therapies (i.e., chemotherapy and radiation therapy) target the actively proliferating cells in tumor masses, which in many cases inevitably induce therapy-resistant cancer cells. It is conceivable that promising therapy regimens can be developed by treating human cancers by inducing terminal differentiation, thereby restoring the interrupted pathway and shifting the balance from proliferation to differentiation. For example, osteosarcoma (OS) is a primary bone cancer caused by differentiation defects in mesenchymal stem cells (MSCs) for which several differentiation therapies have shown great promise. In this review, we discuss the various differentiation therapies in the treatment of human sarcomas with a focus on OS. Such therapies hold great promise as they not only inhibit tumorigenesis, but also avoid the adverse effects associated with conventional chemotherapy regimens. Furthermore, it is conceivable that a combination of conventional therapies with differentiation therapy should significantly improve anticancer efficacy and reduce drug-resistance in the clinical management of human cancers, including sarcomas. PMID:26912947

Malignant mesothelioma with squamous differentiation.

PubMed

Tanaka, Hiroyuki; Akiyama, Yutaka; Kitamura, Akiko; Matsumoto, Nobuhiro; Tomita, Masaki; Kataoka, Hiroaki

2018-06-01

We report the autopsy findings of a 58-year-old man with malignant mesothelioma in the left pleural cavity. The patient had a history of asbestos exposure, and the chest computed tomography scan on initial admission demonstrated an extrapleural sign, suggesting a nodular lesion in the chest wall. However, no nodular lesions were detectable in either of his lungs. In spite of chemotherapy, he died 4 months after the initial admission. An autopsy revealed markedly thickened pleura in a large section of the left pleural cavity without visible intrapulmonary primary tumour lesions. Histological examination of a biopsy specimen obtained prior to chemotherapy and that of an autopsy specimen showed that the pleural tumour was composed of a mixture of mesothelioma and tumour cells with squamous differentiation mimicking squamous cell carcinoma. To the best of our knowledge, this is the first case report of mesothelioma with extensive squamous differentiation in the English-language literature. The extensive squamous differentiation reminiscent of squamous cell carcinoma can be a pitfall in the pathological diagnosis of pleural cytology and that of biopsy specimens from patients with mesothelioma. Here, we report autopsy findings of a case of malignant mesothelioma with portions of extensive squamous differentiation, mimicking a squamous cell carcinoma. © 2018 John Wiley & Sons Ltd.

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.

Metabolic reprogramming during neuronal differentiation

PubMed Central

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

2016-01-01

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

Differentiated Storytelling: From Focused Observation to Strategic Teaching

ERIC Educational Resources Information Center

Abilock, Debbie, Ed.

2008-01-01

Differentiated teaching focuses on the student--the varying needs, interests and abilities in the classroom--in order to design curriculum which results in student understanding through application. Some differentiation implementations are little more than tweaks, but if one is ambitious, differentiation modifications can require substantial time…

21 CFR 864.5220 - Automated differential cell counter.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated differential cell counter. 864.5220... § 864.5220 Automated differential cell counter. (a) Identification. An automated differential cell... have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood...

21 CFR 864.5220 - Automated differential cell counter.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated differential cell counter. 864.5220... § 864.5220 Automated differential cell counter. (a) Identification. An automated differential cell... have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood...

21 CFR 864.5220 - Automated differential cell counter.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated differential cell counter. 864.5220... § 864.5220 Automated differential cell counter. (a) Identification. An automated differential cell... have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood...

21 CFR 864.5220 - Automated differential cell counter.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated differential cell counter. 864.5220... § 864.5220 Automated differential cell counter. (a) Identification. An automated differential cell... have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood...

21 CFR 864.5220 - Automated differential cell counter.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated differential cell counter. 864.5220... § 864.5220 Automated differential cell counter. (a) Identification. An automated differential cell... have the capability to flag, count, or classify immature or abnormal hematopoietic cells of the blood...

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.

Differential effects of Notch ligands Delta-1 and Jagged-1 in human lymphoid differentiation.

PubMed

Jaleco, A C; Neves, H; Hooijberg, E; Gameiro, P; Clode, N; Haury, M; Henrique, D; Parreira, L

2001-10-01

Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis.

Differential Effects of Notch Ligands Delta-1 and Jagged-1 in Human Lymphoid Differentiation

PubMed Central

Jaleco, Ana C.; Neves, Hélia; Hooijberg, Erik; Gameiro, Paula; Clode, Nuno; Haury, Matthias; Henrique, Domingos; Parreira, Leonor

2001-01-01

Notch signaling is known to differentially affect the development of lymphoid B and T cell lineages, but it remains unclear whether such effects are specifically dependent on distinct Notch ligands. Using a cell coculture assay we observed that the Notch ligand Delta-1 completely inhibits the differentiation of human hematopoietic progenitors into the B cell lineage while promoting the emergence of cells with a phenotype of T cell/natural killer (NK) precursors. In contrast, Jagged-1 did not disturb either B or T cell/NK development. Furthermore, cells cultured in the presence of either Delta-1 or Jagged-1 can acquire a phenotype of NK cells, and Delta-1, but not Jagged-1, permits the emergence of a de novo cell population coexpressing CD4 and CD8. Our results thus indicate that distinct Notch ligands can mediate differential effects of Notch signaling and provide a useful system to further address cell-fate decision processes in lymphopoiesis. PMID:11581320

Differentiated Instruction: An Analysis of Approaches and Applications

ERIC Educational Resources Information Center

Smeeton, Gina

2016-01-01

The purpose of this study was to find common perceptions and practices of differentiated instruction by fifth grade teachers. Currently, there is little research on the perspectives of teachers who are learning about and utilizing differentiated instruction in the classroom. This study reviews teacher perceptions about differentiated instruction,…

Variability Analysis of MOS Differential Amplifier

NASA Astrophysics Data System (ADS)

Aoki, Masakazu; Seto, Kenji; Yamawaki, Taizo; Tanaka, Satoshi

Variation characteristics in MOS differential amplifier are evaluated by using the concise statistical model parameters for SPICE simulation. We find that the variation in the differential-mode gain, Adm, induced by the current factor variation, Δβ0, in the Id-variation of the differential MOS transistors is more than one order of magnitude larger than that induced by the threshold voltage variation, ΔVth, which has been regarded as a major factor for circuit variations in SoC's (2). The results obtained by the Monte Carlo simulations are verified by the theoretical analysis combined with the sensitivity analysis which clarifies the specific device parameter dependences of the variation in Adm.

YAP regulates neuronal differentiation through Sonic hedgehog signaling pathway

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yi-Ting; Ding, Jing-Ya; Li, Ming-Yang

2012-09-10

Tight regulation of cell numbers by controlling cell proliferation and apoptosis is important during development. Recently, the Hippo pathway has been shown to regulate tissue growth and organ size in Drosophila. In mammalian cells, it also affects cell proliferation and differentiation in various tissues, including the nervous system. Interplay of several signaling cascades, such as Notch, Wnt, and Sonic Hedgehog (Shh) pathways, control cell proliferation during neuronal differentiation. However, it remains unclear whether the Hippo pathway coordinates with other signaling cascades in regulating neuronal differentiation. Here, we used P19 cells, a mouse embryonic carcinoma cell line, as a model tomore » study roles of YAP, a core component of the Hippo pathway, in neuronal differentiation. P19 cells can be induced to differentiate into neurons by expressing a neural bHLH transcription factor gene Ascl1. Our results showed that YAP promoted cell proliferation and inhibited neuronal differentiation. Expression of Yap activated Shh but not Wnt or Notch signaling activity during neuronal differentiation. Furthermore, expression of Yap increased the expression of Patched homolog 1 (Ptch1), a downstream target of the Shh signaling. Knockdown of Gli2, a transcription factor of the Shh pathway, promoted neuronal differentiation even when Yap was over-expressed. We further demonstrated that over-expression of Yap inhibited neuronal differentiation in primary mouse cortical progenitors and Gli2 knockdown rescued the differentiation defect in Yap over-expressing cells. In conclusion, our study reveals that Shh signaling acts downstream of YAP in regulating neuronal differentiation. -- Highlights: Black-Right-Pointing-Pointer YAP promotes cell proliferation and inhibits neuronal differentiation in P19 cells. Black-Right-Pointing-Pointer YAP promotes Sonic hedgehog signaling activity during neuronal differentiation. Black-Right-Pointing-Pointer Knockdown of Gli2 rescues the

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.

Differential expression analysis of genes involved in high-temperature induced sex differentiation in Nile tilapia.

PubMed

Li, Chun Ge; Wang, Hui; Chen, Hong Ju; Zhao, Yan; Fu, Pei Sheng; Ji, Xiang Shan

2014-01-01

Nowadays, high temperature effects on the molecular pathways during sex differentiation in teleosts need to be deciphered. In this study, a systematic differential expression analysis of genes involved in high temperature-induced sex differentiation was done in the Nile tilapia gonad and brain. Our results showed that high temperature caused significant down-regulation of CYP19A1A in the gonad of both sexes in induction group, and FOXL2 in the ovary of the induction group. The expressions of GTHα, LHβ and ERα were also significantly down-regulated in the brain of both sexes in the induction and recovery groups. On the contrary, the expression of CYP11B2 was significantly up-regulated in the ovary, but not in the testis in both groups. Spearman rank correlation analysis showed that there are significant correlations between the expressions of CYP19A1A, FOXL2, or DMRT1 in the gonads and the expression of some genes in the brain. Another result in this study showed that high temperature up-regulated the expression level of DNMT1 in the testis of the induction group, and DNMT1 and DNMT3A in the female brain of both groups. The expression and correlation analysis of HSPs showed that high temperature action on tilapia HSPs might indirectly induce the expression changes of sex differentiation genes in the gonads. These findings provide new insights on TSD and suggest that sex differentiation related genes, heat shock proteins, and DNA methylation genes are new candidates for studying TSD in fish species. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification of differentially expressed genes associated with differential body size in mandarin fish (Siniperca chuatsi).

PubMed

Tian, Changxu; Li, Ling; Liang, Xu-Fang; He, Shan; Guo, Wenjie; Lv, Liyuan; Wang, Qingchao; Song, Yi

2016-08-01

Body size is an obvious and important characteristic of fish. Mandarin fish Siniperca chuatsi (Basilewsky) is one of the most valuable perciform species widely cultured in China. Individual differences in body size are common in mandarin fish and significantly influence the aquaculture production. However, little is currently known about its genetic control. In this study, digital gene expression profiling and transcriptome sequencing were performed in mandarin fish with differential body size at 30 and 180 days post-hatch (dph), respectively. Body weight, total length and body length of fish with big-size were significantly higher than those with small-size at both 30 and 180 dph (P < 0.05). 2171 and 2014 differentially expressed genes were identified between small-size and big-size fish at 30 and 180 dph, respectively. RT quantitative PCR (qPCR) analysis showed that the differential expression of 10 selected genes in mandarin fish that went through the same training procedure. The genes were involved in the growth hormone-insulin-like growth factor axis, cell proliferation and differentiation, appetite control, glucose metabolism, reproduction and sexual size dimorphism pathways. This study will help toward a comprehensive understanding of the complexity of regulation of body size in mandarin fish individuals and provide valuable information for future research.

Differentiated Instruction in Reading: Easier than It Looks!

ERIC Educational Resources Information Center

Knowles, Liz

2009-01-01

Differentiated instruction has been around for over fifteen years, and like many educational practices, the attention to it is cyclical. In this article, the author talks about how differentiated instruction is used to teach reading. The author also talks about the role of library media specialists in differentiated instruction in reading.

Differentiated Instruction: Understanding the Personal Factors and Organizational Conditions that Facilitate Differentiated Instruction in Elementary Mathematics Classrooms

ERIC Educational Resources Information Center

Abbati, Diana Guglielmo

2012-01-01

Differentiated instruction is a widely held practice used by teachers to provide diverse learners with complex learning opportunities in the area of mathematics. Research on differentiated instruction shows a multitude of factors that support high quality instruction in mixed-ability elementary classrooms. These factors include small-class size,…

Differential calculus on quantized simple lie groups

NASA Astrophysics Data System (ADS)

Jurčo, Branislav

1991-07-01

Differential calculi, generalizations of Woronowicz's four-dimensional calculus on SU q (2), are introduced for quantized classical simple Lie groups in a constructive way. For this purpose, the approach of Faddeev and his collaborators to quantum groups was used. An equivalence of Woronowicz's enveloping algebra generated by the dual space to the left-invariant differential forms and the corresponding quantized universal enveloping algebra, is obtained for our differential calculi. Real forms for q ∈ ℝ are also discussed.

Multiple-Bit Differential Detection of OQPSK

NASA Technical Reports Server (NTRS)

Simon, Marvin

2005-01-01

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

Centriole, differentiation, and senescence.

PubMed

Tkemaladze, J; Chichinadze, K

2010-01-01

Irreversible differentiation (change of morphogenetic status) and programmed death (apoptosis) are observed only in somatic cells, and cell division is the only way by which the morphogenetic status of the offspring cells may be modified. It is known that there is a fixed limit to the number of possible cell divisions, the so-called Hayflick limit. Existing links between cell division, differentiation, and apoptosis make it possible to conclude that all of these processes could be controlled by a single self-reproducing structure. Potential candidates for this replicable structure in a somatic cell are the chromosomes, mitochondria (both contain DNA), and centrioles. Centrioles (a diplosome, or pair of centrioles) are the most likely unit that can fully regulate the processes of irreversible differentiation, determination, and modification of the morphogenetic status. Centrioles may contain differently encoded RNA molecules stacked in a definite order, and during mitosis, these RNA molecules are released one by one into the cytoplasm. In the presence of reverse transcriptase and endonuclease, processing of this RNA presumably changes the status of repressed and potentially active genes and, subsequently, the morphogenetic status of a cell.

Update on Waveguide-Embedded Differential MMIC Amplifiers

NASA Technical Reports Server (NTRS)

Kangaslahti, Pekka; Schleht, Erich

2010-01-01

There is an update on the subject matter of Differential InP HEMT MMIC Amplifiers Embedded in Waveguides (NPO-42857) NASA Tech Briefs, Vol. 33, No. 9 (September 2009), page 35. To recapitulate: Monolithic microwave integrated-circuit (MMIC) amplifiers of a type now being developed for operation at frequencies of hundreds of gigahertz contain InP high-electron-mobility transistors (HEMTs) in a differential configuration. The MMICs are designed integrally with, and embedded in, waveguide packages. The instant work does not mention InP HEMTs but otherwise reiterates part of the subject matter of the cited prior article, with emphasis on the following salient points: An MMIC is mounted in the electric-field plane ("E-plane") of a waveguide and includes a finline transition to each differential-amplifier stage. The differential configuration creates a virtual ground within each pair of transistor-gate fingers, eliminating the need for external radio-frequency grounding. This work concludes by describing a single-stage differential submillimeter-wave amplifier packaged in a rectangular waveguide and summarizing results of tests of this amplifier at frequencies of 220 and 305 GHz.

Inference for High-dimensional Differential Correlation Matrices *

PubMed Central

Cai, T. Tony; Zhang, Anru

2015-01-01

Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed. PMID:26500380

Inference for High-dimensional Differential Correlation Matrices.

PubMed

Cai, T Tony; Zhang, Anru

2016-01-01

Motivated by differential co-expression analysis in genomics, we consider in this paper estimation and testing of high-dimensional differential correlation matrices. An adaptive thresholding procedure is introduced and theoretical guarantees are given. Minimax rate of convergence is established and the proposed estimator is shown to be adaptively rate-optimal over collections of paired correlation matrices with approximately sparse differences. Simulation results show that the procedure significantly outperforms two other natural methods that are based on separate estimation of the individual correlation matrices. The procedure is also illustrated through an analysis of a breast cancer dataset, which provides evidence at the gene co-expression level that several genes, of which a subset has been previously verified, are associated with the breast cancer. Hypothesis testing on the differential correlation matrices is also considered. A test, which is particularly well suited for testing against sparse alternatives, is introduced. In addition, other related problems, including estimation of a single sparse correlation matrix, estimation of the differential covariance matrices, and estimation of the differential cross-correlation matrices, are also discussed.

Differanisole A, an inducer of the differentiation of Friend leukemic cells, induces stalk cell differentiation in Dictyostelium discoideum.

PubMed

Kubohara, Y; Okamoto, K; Tanaka, Y; Asahi, K; Sakurai, A; Takahashi, N

1993-05-03

Differanisole A isolated from the conditioned medium of a soil microorganism, Chaetomium strain RB-001, is an inducer of the differentiation of the Friend leukemic cells (mouse leukemia cells). The chemical structure of this substance is very similar to that of stalk cell differentiation-inducing factor (DIF) isolated from the cellular slime mould, Dictyostelium discoideum. We examined the effects of differanisole A on Dictyostelium HM44 cells, a mutant strain which is defective in DIF production, and found this substance to be an inducer of stalk cell differentiation in D. discoideum.

Differential campsite pricing and campground attendance

Treesearch

Wilbur F. LaPage; Paula L. Cormier; George T. Hamilton; Alan D. Cormier

1975-01-01

Several changes in the characteristics of campers' visits were discovered by comparing camping permit data before and after the start of differential campsite pricing at a New Hampshire state park campground in 1973. Differentials included a premium charge for waterfront sites and a preferential rate for New Hampshire residents. Attendance by state residents...

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…

NURR1 Downregulation Favors Osteoblastic Differentiation of MSCs

PubMed Central

Di Benedetto, Adriana; Cantore, Stefania; Centonze, Matteo; Grano, Maria; Cavalcanti-Adam, Elisabetta A.

2017-01-01

Mesenchymal stem cells (MSCs) have been identified in human dental tissues. Dental pulp stem cells (DPSCs) were classified within MSC family, are multipotent, can be isolated from adult teeth, and have been shown to differentiate, under particular conditions, into various cell types including osteoblasts. In this work, we investigated how the differentiation process of DPSCs toward osteoblasts is controlled. Recent literature data attributed to the nuclear receptor related 1 (NURR1), a still unclarified role in osteoblast differentiation, while NURR1 is primarily involved in dopaminergic neuron differentiation and activity. Thus, in order to verify if NURR1 had a role in DPSC osteoblastic differentiation, we silenced it during all the processes and compared the expression of the main osteoblastic markers with control cultures. Our results showed that the inhibition of NURR1 significantly increased the expression of osteoblast markers collagen I and alkaline phosphatase. Further, in long time cultures, the mineral matrix deposition was strongly enhanced in NURR1-silenced cultures. These results suggest that NURR1 plays a key role in switching DPSC differentiation toward osteoblasts rather than neuronal or even other cell lines. In conclusion, DPSCs represent a source of osteoblast-like cells and downregulation of NURR1 strongly prompted their differentiation toward the osteoblastogenesis process. PMID:28769982

On implicit abstract neutral nonlinear differential equations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hernández, Eduardo, E-mail: lalohm@ffclrp.usp.br; O’Regan, Donal, E-mail: donal.oregan@nuigalway.ie

2016-04-15

In this paper we continue our developments in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) on the existence of solutions for abstract neutral differential equations. In particular we extend the results in Hernández and O’Regan (J Funct Anal 261:3457–3481, 2011) for the case of implicit nonlinear neutral equations and we focus on applications to partial “nonlinear” neutral differential equations. Some applications involving partial neutral differential equations are presented.

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.

Soft matrix supports osteogenic differentiation of human dental follicle cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Viale-Bouroncle, Sandra; Voellner, Florian; Moehl, Christoph

Highlights: {yields} Rigid stiffness supports osteogenic differentiation in mesenchymal stem cells (MSCs). {yields} Our study examined stiffness and differentiation of dental follicle cells (DFCs). {yields} Soft ECMs have a superior capacity to support the osteogenic differentiation of DFCs. {yields} DFCs and MSCs react contrarily to soft and rigid surface stiffness. -- Abstract: The differentiation of stem cells can be directed by the grade of stiffness of the developed tissue cells. For example a rigid extracellular matrix supports the osteogenic differentiation in bone marrow derived mesenchymal stem cells (MSCs). However, less is known about the relation of extracellular matrix stiffness andmore » cell differentiation of ectomesenchymal dental precursor cells. Our study examined for the first time the influence of the surface stiffness on the proliferation and osteogenic differentiation of human dental follicle cells (DFCs). Cell proliferation of DFCs was only slightly decreased on cell culture surfaces with a bone-like stiffness. The osteogenic differentiation in DFCs could only be initiated with a dexamethasone based differentiation medium after using varying stiffness. Here, the softest surface improved the induction of osteogenic differentiation in comparison to that with the highest stiffness. In conclusion, different to bone marrow derived MSCs, soft ECMs have a superior capacity to support the osteogenic differentiation of DFCs.« less

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…

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.

Dendritic cell MST1 inhibits Th17 differentiation

PubMed Central

Li, Chunxiao; Bi, Yujing; Li, Yan; Yang, Hui; Yu, Qing; Wang, Jian; Wang, Yu; Su, Huilin; Jia, Anna; Hu, Ying; Han, Linian; Zhang, Jiangyuan; Li, Simin; Tao, Wufan; Liu, Guangwei

2017-01-01

Although the differentiation of CD4+T cells is widely studied, the mechanisms of antigen-presenting cell-dependent T-cell modulation are unclear. Here, we investigate the role of dendritic cell (DC)-dependent T-cell differentiation in autoimmune and antifungal inflammation and find that mammalian sterile 20-like kinase 1 (MST1) signalling from DCs negatively regulates IL-17 producing-CD4+T helper cell (Th17) differentiation. MST1 deficiency in DCs increases IL-17 production by CD4+T cells, whereas ectopic MST1 expression in DCs inhibits it. Notably, MST1-mediated DC-dependent Th17 differentiation regulates experimental autoimmune encephalomyelitis and antifungal immunity. Mechanistically, MST1-deficient DCs promote IL-6 secretion and regulate the activation of IL-6 receptor α/β and STAT3 in CD4+T cells in the course of inducing Th17 differentiation. Activation of the p38 MAPK signal is responsible for IL-6 production in MST1-deficient DCs. Thus, our results define the DC MST1–p38MAPK signalling pathway in directing Th17 differentiation. PMID:28145433

Automated numerical simulation of biological pattern formation based on visual feedback simulation framework.

PubMed

Sun, Mingzhu; Xu, Hui; Zeng, Xingjuan; Zhao, Xin

2017-01-01

There are various fantastic biological phenomena in biological pattern formation. Mathematical modeling using reaction-diffusion partial differential equation systems is employed to study the mechanism of pattern formation. However, model parameter selection is both difficult and time consuming. In this paper, a visual feedback simulation framework is proposed to calculate the parameters of a mathematical model automatically based on the basic principle of feedback control. In the simulation framework, the simulation results are visualized, and the image features are extracted as the system feedback. Then, the unknown model parameters are obtained by comparing the image features of the simulation image and the target biological pattern. Considering two typical applications, the visual feedback simulation framework is applied to fulfill pattern formation simulations for vascular mesenchymal cells and lung development. In the simulation framework, the spot, stripe, labyrinthine patterns of vascular mesenchymal cells, the normal branching pattern and the branching pattern lacking side branching for lung branching are obtained in a finite number of iterations. The simulation results indicate that it is easy to achieve the simulation targets, especially when the simulation patterns are sensitive to the model parameters. Moreover, this simulation framework can expand to other types of biological pattern formation.

Automated numerical simulation of biological pattern formation based on visual feedback simulation framework

PubMed Central

Sun, Mingzhu; Xu, Hui; Zeng, Xingjuan; Zhao, Xin

2017-01-01

There are various fantastic biological phenomena in biological pattern formation. Mathematical modeling using reaction-diffusion partial differential equation systems is employed to study the mechanism of pattern formation. However, model parameter selection is both difficult and time consuming. In this paper, a visual feedback simulation framework is proposed to calculate the parameters of a mathematical model automatically based on the basic principle of feedback control. In the simulation framework, the simulation results are visualized, and the image features are extracted as the system feedback. Then, the unknown model parameters are obtained by comparing the image features of the simulation image and the target biological pattern. Considering two typical applications, the visual feedback simulation framework is applied to fulfill pattern formation simulations for vascular mesenchymal cells and lung development. In the simulation framework, the spot, stripe, labyrinthine patterns of vascular mesenchymal cells, the normal branching pattern and the branching pattern lacking side branching for lung branching are obtained in a finite number of iterations. The simulation results indicate that it is easy to achieve the simulation targets, especially when the simulation patterns are sensitive to the model parameters. Moreover, this simulation framework can expand to other types of biological pattern formation. PMID:28225811

Exact-Differential Large-Scale Traffic Simulation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hanai, Masatoshi; Suzumura, Toyotaro; Theodoropoulos, Georgios

2015-01-01

Analyzing large-scale traffics by simulation needs repeating execution many times with various patterns of scenarios or parameters. Such repeating execution brings about big redundancy because the change from a prior scenario to a later scenario is very minor in most cases, for example, blocking only one of roads or changing the speed limit of several roads. In this paper, we propose a new redundancy reduction technique, called exact-differential simulation, which enables to simulate only changing scenarios in later execution while keeping exactly same results as in the case of whole simulation. The paper consists of two main efforts: (i) amore » key idea and algorithm of the exact-differential simulation, (ii) a method to build large-scale traffic simulation on the top of the exact-differential simulation. In experiments of Tokyo traffic simulation, the exact-differential simulation shows 7.26 times as much elapsed time improvement in average and 2.26 times improvement even in the worst case as the whole simulation.« less

Cancer stem cells and differentiation therapy.

PubMed

Jin, Xiong; Jin, Xun; Kim, Hyunggee

2017-10-01

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

Exotic differentiable structures and general relativity

NASA Astrophysics Data System (ADS)

Brans, Carl H.; Randall, Duane

1993-02-01

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

Differential memory in the earth's magnetotail

NASA Technical Reports Server (NTRS)

Burkhart, G. R.; Chen, J.

1991-01-01

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

COMPENSATIONAL THREE-WAVELENGTH DIFFERENTIAL-ABSORPTION LIDAR TECHNIQUE FOR REDUCING THE INFLUENCE OF DIFFERENTIAL SCATTERING ON OZONE-CONCENTRATION MEASUREMENTS.

EPA Science Inventory

A three-wavelength differential-absorption lidar (DIAL) technique for the UV spectral region is presented that reduces the influence of aerosol differential scattering on measured O3-concentration profiles. The principal advantage of this approach is that, to a good first approxi...

Blood Differential: MedlinePlus Lab Test Information

MedlinePlus

... Test Information → Blood Differential URL of this page: https://medlineplus.gov/labtests/blooddifferential.html Blood Differential To ... 2015 Oct [cited 2017 Jan 25]. Available from: http://www.ebmconsult.com/articles/glucocorticoid-wbc-increase-steroids ...

Retinoic acid and nitric oxide promote cell proliferation and differentially induce neuronal differentiation in vitro in the cnidarian Renilla koellikeri.

PubMed

Estephane, Djoyce; Anctil, Michel

2010-10-01

Retinoic acid (RA) and nitric oxide (NO) are known to promote neuronal development in both vertebrates and invertebrates. Retinoic acid receptors appear to be present in cnidarians and NO plays various physiological roles in several cnidarians, but there is as yet no evidence that these agents have a role in neural development in this basal metazoan phylum. We used primary cultures of cells from the sea pansy Renilla koellikeri to investigate the involvement of these signaling molecules in cnidarian cell differentiation. We found that 9-cis RA induce cell proliferation in dose- and time-dependent manners in dishes coated with polylysine from the onset of culture. Cells in cultures exposed to RA in dishes devoid of polylysine were observed to differentiate into epithelium-associated cells, including sensory cells, without net gain in cell density. NO donors also induce cell proliferation in polylysine-coated dishes, but induce neuronal differentiation and neurite outgrowth in uncoated dishes. No other cell type undergoes differentiation in the presence of NO. These observations suggest that in the sea pansy (1) cell adhesion promotes proliferation without morphogenesis and this proliferation is modulated positively by 9-cis RA and NO, (2) 9-cis RA and NO differentially induce neuronal differentiation in nonadherent cells while repressing proliferation, and (3) the involvement of RA and NO in neuronal differentiation appeared early during the evolutionary emergence of nervous systems. 2010 Wiley Periodicals, Inc.

Solution of some types of differential equations: operational calculus and inverse differential operators.

PubMed

Zhukovsky, K

2014-01-01

We present a general method of operational nature to analyze and obtain solutions for a variety of equations of mathematical physics and related mathematical problems. We construct inverse differential operators and produce operational identities, involving inverse derivatives and families of generalised orthogonal polynomials, such as Hermite and Laguerre polynomial families. We develop the methodology of inverse and exponential operators, employing them for the study of partial differential equations. Advantages of the operational technique, combined with the use of integral transforms, generating functions with exponentials and their integrals, for solving a wide class of partial derivative equations, related to heat, wave, and transport problems, are demonstrated.

Thinking Differentially: A Response to Issues in Differential Response

ERIC Educational Resources Information Center

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

2013-01-01

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

Differential expression of neuroleukin in osseous tissues and its involvement in mineralization during osteoblast differentiation

NASA Technical Reports Server (NTRS)

Zhi, J.; Sommerfeldt, D. W.; Rubin, C. T.; Hadjiargyrou, M.

2001-01-01

Osteoblast differentiation is a multistep process that involves critical spatial and temporal regulation of cellular processes marked by the presence of a large number of differentially expressed molecules. To identify key functional molecules, we used differential messenger RNA (mRNA) display and compared RNA populations isolated from the defined transition phases (proliferation, matrix formation, and mineralization) of the MC3T3-E1 osteoblast-like cell line. Using this approach, a complementary DNA (cDNA) fragment was isolated and identified as neuroleukin (NLK), a multifunctional cytokine also known as autocrine motility factor (AMF), phosphoglucose isomerase (PGI; phosphohexose isomerase [PHI]), and maturation factor (MF). Northern analysis showed NLK temporal expression during MC3T3-E1 cell differentiation with a 3.5-fold increase during matrix formation and mineralization. Immunocytochemical studies revealed the presence of NLK in MC3T3-E1 cells as well as in the surrounding matrix, consistent with a secreted molecule. In contrast, the NLK receptor protein was detected primarily on the cell membrane. In subsequent studies, a high level of NLK expression was identified in osteoblasts and superficial articular chondrocytes in bone of 1-, 4-, and 8-month-old normal mice, as well as in fibroblasts, proliferating chondrocytes, and osteoblasts within a fracture callus. However, NLK was not evident in hypertrophic chondrocytes or osteocytes. In addition, treatment of MC3T3 cells with 6-phosphogluconic acid (6PGA; a NLK inhibitor) resulted in diminishing alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, especially during the matrix formation stage of differentiating cells. Taken together, these data show specific expression of NLK in discrete populations of bone and cartilage cells and suggest a possible role for this secreted protein in bone development and regeneration.

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…

Differential phase measurements of D-region partial reflections

NASA Technical Reports Server (NTRS)

Wiersma, D. J.; Sechrist, C. F., Jr.

1972-01-01

Differential phase partial reflection measurements were used to deduce D region electron density profiles. The phase difference was measured by taking sums and differences of amplitudes received on an array of crossed dipoles. The reflection model used was derived from Fresnel reflection theory. Seven profiles obtained over the period from 13 October 1971 to 5 November 1971 are presented, along with the results from simultaneous measurements of differential absorption. Some possible sources of error and error propagation are discussed. A collision frequency profile was deduced from the electron concentration calculated from differential phase and differential absorption.

Differential principal component analysis of ChIP-seq.

PubMed

Ji, Hongkai; Li, Xia; Wang, Qian-fei; Ning, Yang

2013-04-23

We propose differential principal component analysis (dPCA) for analyzing multiple ChIP-sequencing datasets to identify differential protein-DNA interactions between two biological conditions. dPCA integrates unsupervised pattern discovery, dimension reduction, and statistical inference into a single framework. It uses a small number of principal components to summarize concisely the major multiprotein synergistic differential patterns between the two conditions. For each pattern, it detects and prioritizes differential genomic loci by comparing the between-condition differences with the within-condition variation among replicate samples. dPCA provides a unique tool for efficiently analyzing large amounts of ChIP-sequencing data to study dynamic changes of gene regulation across different biological conditions. We demonstrate this approach through analyses of differential chromatin patterns at transcription factor binding sites and promoters as well as allele-specific protein-DNA interactions.

Differential rotation in Jupiter: A comparison of methods

NASA Astrophysics Data System (ADS)

Wisdom, J.; Hubbard, W. B.

2016-03-01

Whether Jupiter rotates as a solid body or has some element of differential rotation along concentric cylinders is unknown. But Jupiter's zonal wind is not north/south symmetric so at most some average of the north/south zonal winds could be an expression of cylinders. Here we explore the signature in the gravitational moments of such a smooth differential rotation. We carry out this investigation with two general methods for solving for the interior structure of a differentially rotating planet: the CMS method of Hubbard (Hubbard, W.B. [2013]. Astrophys. J. 768, 1-8) and the CLC method of Wisdom (Wisdom, J. [1996]. Non-Perturbative Hydrostatic Equilibrium. http://web.mit.edu/wisdom/www/interior.pdf). The two methods are in remarkable agreement. We find that for smooth differential rotation the moments do not level off as they do for strong differential rotation.

Fourier transform infrared spectroscopic analysis of cell differentiation

NASA Astrophysics Data System (ADS)

Ishii, Katsunori; Kimura, Akinori; Kushibiki, Toshihiro; Awazu, Kunio

2007-02-01

Stem cells and its differentiations have got a lot of attentions in regenerative medicine. The process of differentiations, the formation of tissues, has become better understood by the study using a lot of cell types progressively. These studies of cells and tissue dynamics at molecular levels are carried out through various approaches like histochemical methods, application of molecular biology and immunology. However, in case of using regenerative sources (cells, tissues and biomaterials etc.) clinically, they are measured and quality-controlled by non-invasive methods from the view point of safety. Recently, the use of Fourier Transform Infrared spectroscopy (FT-IR) has been used to monitor biochemical changes in cells, and has gained considerable importance. The objective of this study is to establish the infrared spectroscopy of cell differentiation as a quality control of cell sources for regenerative medicine. In the present study, as a basic study, we examined the adipose differentiation kinetics of preadipocyte (3T3-L1) and the osteoblast differentiation kinetics of bone marrow mesenchymal stem cells (Kusa-A1) to analyze the infrared absorption spectra. As a result, we achieved to analyze the adipose differentiation kinetics using the infrared absorption peak at 1739 cm-1 derived from ester bonds of triglyceride and osteoblast differentiation kinetics using the infrared absorption peak at 1030 cm-1 derived from phosphate groups of calcium phosphate.

Different level of population differentiation among human genes.

PubMed

Wu, Dong-Dong; Zhang, Ya-Ping

2011-01-14

During the colonization of the world, after dispersal out of African, modern humans encountered changeable environments and substantial phenotypic variations that involve diverse behaviors, lifestyles and cultures, were generated among the different modern human populations. Here, we study the level of population differentiation among different populations of human genes. Intriguingly, genes involved in osteoblast development were identified as being enriched with higher FST SNPs, a result consistent with the proposed role of the skeletal system in accounting for variation among human populations. Genes involved in the development of hair follicles, where hair is produced, were also found to have higher levels of population differentiation, consistent with hair morphology being a distinctive trait among human populations. Other genes that showed higher levels of population differentiation include those involved in pigmentation, spermatid, nervous system and organ development, and some metabolic pathways, but few involved with the immune system. Disease-related genes demonstrate excessive SNPs with lower levels of population differentiation, probably due to purifying selection. Surprisingly, we find that Mendelian-disease genes appear to have a significant excessive of SNPs with high levels of population differentiation, possibly because the incidence and susceptibility of these diseases show differences among populations. As expected, microRNA regulated genes show lower levels of population differentiation due to purifying selection. Our analysis demonstrates different level of population differentiation among human populations for different gene groups.

Atmospheres of partially differentiated super-Earth exoplanets

NASA Astrophysics Data System (ADS)

Schaefer, Laura; Sasselov, Dimitar

2015-11-01

Terrestrial exoplanets have been discovered in a range of sizes, densities and orbital locations that defy our expectations based upon the Solar System. Planets discovered to date with radii less than ~1.5-1.6 Earth radii all seem to fall on an iso-density curve with the Earth [1]. However, mass and radius determinations, which depend on the known properties of the host star, are not accurate enough to distinguish between a fully differentiated three-layer planet (core, mantle, ocean/atmosphere) and an incompletely differentiated planet [2]. Full differentiation of a planet will depend upon the conditions at the time of accretion, including the abundance of short-lived radioisotopes, which will vary from system to system, as well as the number of giant impacts the planet experiences. Furthermore, separation of metal and silicates at the much larger pressures found inside super-Earths will depend on how the chemistry of these materials change at high pressures. There are therefore hints emerging that not all super-Earths will be fully differentiated. Incomplete differentiation will result in a more reduced mantle oxidation state and may have implications for the composition of an outgassed atmosphere. Here we will present the first results from a chemical equilibrium model of the composition of such an outgassed atmosphere and discuss the possibility of distinguishing between fully and incompletely differentiated planets through atmospheric observations.[1] Rogers, L. 2015. ApJ, 801, 41. [2] Zeng, L. & Sasselov, D. 2013. PASP, 125, 227.

Differential phase acoustic microscope for micro-NDE

NASA Technical Reports Server (NTRS)

Waters, David D.; Pusateri, T. L.; Huang, S. R.

1992-01-01

A differential phase scanning acoustic microscope (DP-SAM) was developed, fabricated, and tested in this project. This includes the acoustic lens and transducers, driving and receiving electronics, scanning stage, scanning software, and display software. This DP-SAM can produce mechanically raster-scanned acoustic microscopic images of differential phase, differential amplitude, or amplitude of the time gated returned echoes of the samples. The differential phase and differential amplitude images provide better image contrast over the conventional amplitude images. A specially designed miniature dual beam lens was used to form two foci to obtain the differential phase and amplitude information of the echoes. High image resolution (1 micron) was achieved by applying high frequency (around 1 GHz) acoustic signals to the samples and placing two foci close to each other (1 micron). Tone burst was used in this system to obtain a good estimation of the phase differences between echoes from the two adjacent foci. The system can also be used to extract the V(z) acoustic signature. Since two acoustic beams and four receiving modes are available, there are 12 possible combinations to produce an image or a V(z) scan. This provides a unique feature of this system that none of the existing acoustic microscopic systems can provide for the micro-nondestructive evaluation applications. The entire system, including the lens, electronics, and scanning control software, has made a competitive industrial product for nondestructive material inspection and evaluation and has attracted interest from existing acoustic microscope manufacturers.

Test of CCD Precision Limits for Differential Photometry

NASA Technical Reports Server (NTRS)

Borucki, W. J.; Dunham, E. W.; Wei, M. Z.; Robinson, L. B.; Ford, C. H.; Granados, A. F.

1995-01-01

Results of tests to demonstrate the very high differential-photometric stability of CCD light sensors are presented. The measurements reported here demonstrate that in a controlled laboratory environment, a front-illuminated CCD can provide differential-photometric measurements with reproducible precision approaching one part in 105. Practical limitations to the precision of differential-photometric measurements with CCDs and implications for spaceborne applications are discussed.

Melanoma with rhabdomyosarcomatous differentiation.

PubMed

Kuwadekar, Aditya; Allard, Justin; Dardik, Michael; Smith, Franz

2018-06-06

Melanoma with rhabdomyosarcomatous differentiation is an extremely rare observation with a review of the literature revealing fewer than 15 previously identified cases. The authors describe a case of a 72-year-old man with a cutaneous lesion of the left scalp that was diagnosed as malignant melanoma on biopsy and wide excision. One month later, a punch biopsy of the excisional area revealed rhabdomyosarcomatous proliferation. Re-examination of the wide-excision specimen with muscle markers revealed areas of neoplastic melanoma cells consistent with rhabdomyosarcomatous differentiation. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cancer (stem) cell differentiation: An inherent or acquired property?

PubMed

Mohr, Marieke; Zänker, Kurt S; Dittmar, Thomas

2015-12-01

There is a growing list of data indicating that cancer (stem) cells could functionally adapt foreign tissue features, such as endothelial-like cells or neuroendocrine cells, express lineage markers or could differentiate into various lineages in response to appropriate differentiation criteria. The finding that cancer (stem) cells may possess some kind of differentiation capacity poses the question whether this might be an inherent or acquired property. Cancer stem cells share stem cell characteristics and may thus possess an inherent differentiation capacity enabling the cells to respond to various differentiation stimuli. Considering the plasticity of cancer (stem) cells, even non-tumorigenic (and putatively non-differentiable) tumor cells could give rise to tumorigenic tumor stem cells, exhibiting stem cell characteristics including an inherent differentiation capacity. On the contrary, cancer (stem) cells may have acquired differentiation capacity as a consequence of a previous cell fusion event with cell types exhibiting differentiation potential and being fusogenic, such as macrophages or stem cells. Of pivotal interest in a tumor context are macrophages, which chiefly foster the chronically inflamed tumor microenvironment. Because chronically inflamed tissue is a well-known trigger for cell fusion and both macrophages and stem cells are highly fusogenic we conclude that cell fusion events between these cell types and cancer (stem) cells should frequently occur, thereby giving rise to hybrid cells exhibiting not only novel properties, like an enhanced metastatogenic phenotype, but also parental characteristics, such as differentiation capacity. Conceivably, the combination of both properties might be advantageous for metastasizing cancer (stem) cells to adapt better and faster to a foreign organ tissue environment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Differential formulation of the gyrokinetic Landau operator

DOE PAGES

Hirvijoki, Eero; Brizard, Alain J.; Pfefferlé, David

2017-01-05

Subsequent to the recent rigorous derivation of an energetically consistent gyrokinetic collision operator in the so-called Landau representation, this work investigates the possibility of finding a differential formulation of the gyrokinetic Landau collision operator. It is observed that, while a differential formulation is possible in the gyrokinetic phase space, reduction of the resulting system of partial differential equations to five dimensions via gyroaveraging poses a challenge. Finally, based on the present work, it is likely that the gyrocentre analogues of the Rosenbluth–MacDonald–Judd potential functions must be kept gyroangle dependent.

Differential Rotation via Tracking of Coronal Bright Points.

NASA Astrophysics Data System (ADS)

McAteer, James; Boucheron, Laura E.; Osorno, Marcy

2016-05-01

The accurate computation of solar differential rotation is important both as a constraint for, and evidence towards, support of models of the solar dynamo. As such, the use of Xray and Extreme Ultraviolet bright points to elucidate differential rotation has been studied in recent years. In this work, we propose the automated detection and tracking of coronal bright points (CBPs) in a large set of SDO data for re-evaluation of solar differential rotation and comparison to other results. The big data aspects, and high cadence, of SDO data mitigate a few issues common to detection and tracking of objects in image sequences and allow us to focus on the use of CBPs to determine differential rotation. The high cadence of the data allows to disambiguate individual CBPs between subsequent images by allowing for significant spatial overlap, i.e., by the fact that the CBPs will rotate a short distance relative to their size. The significant spatial overlap minimizes the effects of incorrectly detected CBPs by reducing the occurrence of outlier values of differential rotation. The big data aspects of the data allows to be more conservative in our detection of CBPs (i.e., to err on the side of missing CBPs rather than detecting extraneous CBPs) while still maintaining statistically larger populations over which to study characteristics. The ability to compute solar differential rotation through the automated detection and tracking of a large population of CBPs will allow for further analyses such as the N-S asymmetry of differential rotation, variation of differential rotation over the solar cycle, and a detailed study of the magnetic flux underlying the CBPs.

Age Differences in the Differentiation of Trait Impressions From Faces

PubMed Central

Ng, Stacey Y.; Zebrowitz, Leslie A.; Franklin, Robert G.

2016-01-01

Objectives. We investigated whether evidence that older adults (OA) show less differentiation of visual stimuli than younger adults (YA) extends to trait impressions from faces and effects of face age. We also examined whether age differences in mood, vision, or cognition-mediated differentiation differences. Finally, we investigated whether age differences in trait differentiation mediated differences in impression positivity. Method. We used a differentiation index adapted from previous work on stereotyping to assess OA and YA likelihood of assigning different faces to different levels on trait scales. We computed scores for ratings of older and younger faces’ competence, health, hostility, and untrustworthiness. Results. OA showed less differentiated trait ratings than YA. Measures of mood, vision, and cognition did not mediate these rater age differences. Hostility was differentiated more for younger than older faces, while health was differentiated more for older faces, but only by OA. Age differences in differentiation mediated age differences in impression positivity. Discussion. Less differentiation of trait impressions from faces in OA is consistent with previous evidence for less differentiation in face and emotion recognition. Results indicated that that age-related dedifferentiation does not reflect narrow changes in visual function. They also provide a novel explanation for OA positivity effects. PMID:25194140

Alginate-Encapsulation for the Improved Hypothermic Preservation of Human Adipose-Derived Stem Cells.

PubMed

Swioklo, Stephen; Constantinescu, Andrei; Connon, Che J

2016-03-01

Despite considerable progress within the cell therapy industry, unmet bioprocessing and logistical challenges associated with the storage and distribution of cells between sites of manufacture and the clinic exist. We examined whether hypothermic (4°C-23°C) preservation of human adipose-derived stem cells could be improved through their encapsulation in 1.2% calcium alginate. Alginate encapsulation improved the recovery of viable cells after 72 hours of storage. Viable cell recovery was highly temperature-dependent, with an optimum temperature of 15°C. At this temperature, alginate encapsulation preserved the ability for recovered cells to attach to tissue culture plastic on rewarming, further increasing its effect on total cell recovery. On attachment, the cells were phenotypically normal, displayed normal growth kinetics, and maintained their capacity for trilineage differentiation. The number of cells encapsulated (up to 2 × 10(6) cells per milliliter) did not affect viable cell recovery nor did storage of encapsulated cells in a xeno-free, serum-free,current Good Manufacturing Practice-grade medium. We present a simple, low-cost system capable of enhancing the preservation of human adipose-derived stem cells stored at hypothermic temperatures, while maintaining their normal function. The storage of cells in this manner has great potential for extending the time windows for quality assurance and efficacy testing, distribution between the sites of manufacture and the clinic, and reducing the wastage associated with the limited shelf life of cells stored in their liquid state. ©AlphaMed Press.

Differential exposure and differential vulnerability as counteracting forces linking the psychosocial work environment to socioeconomic health differences.

PubMed

Vanroelen, C; Levecque, K; Louckx, F

2010-10-01

In this article, the link between (1) psychosocial working conditions (job demands, job autonomy, task variation, social support), (2) self-reported health (persistent fatigue, musculoskeletal complaints, emotional well-being) and (3) socioeconomic position (skill levels, occupational status) is explored. The two theoretical pathways linking the psychosocial work environment to socioeconomic differences in health are explored: differential exposure and differential vulnerability. Previously, the focus has often been on social inequalities in exposure to the stressors. The pathway of differential vulnerability in different socioeconomic positions is often neglected. In a representative cross-sectional sample of 11,099 Flemish (Belgian) wage earners, 16-65 years of age (47.5% women), logit modelling is applied. Higher exposure to psychosocial occupational stressors is associated with a higher prevalence of adverse health outcomes. Lower skill levels and subordinate occupational positions show a higher prevalence of musculoskeletal complaints, but not of persistent fatigue or emotional well-being. High demands, job strain and iso-strain are more common in higher-skilled, supervisory and managerial positions, but have the strongest health-damaging effects in lower socioeconomic positions. Low control is more prevalent in lower-skilled and subordinate positions, while having stronger adverse health effects in higher socioeconomic positions-the same holds for social support, although it has no clear socioeconomic distribution. Differential exposure and differential vulnerability constitute two counteracting forces in constituting the association between the psychosocial work environment and socioeconomic differences in self-reported health complaints among wage earners.

Metabolic phenotyping of a model of adipocyte differentiation

PubMed Central

Roberts, Lee D.; Virtue, Sam; Vidal-Puig, Antonio; Nicholls, Andrew W.

2009-01-01

The 3T3-L1 murine cell line is a robust and widely used model for the study of adipogenesis and processes occurring in mature adipocytes. The fibroblastic like cells can be induced by hormones to differentiate into mature adipocytes. In this study, the metabolic phenotype associated with differentiation of the 3T3-L1 cell line has been studied using gas chromatography-mass spectrometry, 1H nuclear magnetic resonance spectroscopy, liquid chromatography-mass spectrometry, direct infusion-mass spectrometry, and 13C substrate labeling in conjunction with multivariate statistics. The changes in metabolite concentrations at distinct periods during differentiation have been defined including alterations in the TCA cycle, glycolysis, the production of odd chain fatty acids by α-oxidation, fatty acid synthesis, fatty acid desaturation, polyamine biosynthesis, and trans-esterification to produce complex lipids. The metabolic changes induced during differentiation of the 3T3-L1 cell line were then compared with the metabolic differences between pre- and postdifferentiation primary adipocytes. These metabolic alterations reflect the changing role of the 3T3-L1 cells during differentiation, as well as possibly providing metabolic triggers to stimulate the processes which occur during differentiation. PMID:19602617

Osteoclast differentiation inhibitors: a patent review (2008 - 2012).

PubMed

Kim, Seong Hwan; Moon, Seong-Hee

2013-12-01

Mononuclear macrophage/monocyte-lineage hematopoietic precursors differentiate into multinucleated osteoclasts. Abnormally increased numbers and/or overactivation of osteoclasts can lead to bone loss. Therefore, pharmaceutical inhibition of osteoclast differentiation is one therapeutic strategy for mitigating the occurrence of bone loss-associated disorders and related fractures. This review surveys the patents and patent applications from 2008 to 2012 that are related to inventions of therapeutics and/or methods for inhibiting osteoclast differentiation. Over the past 20 years, the identification and validation of signaling molecules involved in osteoclast differentiation has led to a better understanding of the molecular mechanism, and to the development of new therapeutic agents for treating bone loss-associated disorders. Since 2008, 34 WO patents or patent applications have been filed that relate to inventions of therapeutics and/or methods for chemical-based, natural product-based, or biological-based inhibitors of osteoclast differentiation. Here, analysis of these patents and patent applications is presented, and summarize the disclosed osteoclast differentiation-inhibiting target molecules. This report can support further advances in the development of anti-osteoclastogenic therapeutics for bone loss-associated disorders, including osteoporosis, rheumatoid arthritis, Paget's disease, periodontal disease, osteosarcoma, and cancer bone metastasis.

The Process of Horizontal Differentiation: Two Models.

ERIC Educational Resources Information Center

Daft, Richard L.; Bradshaw, Patricia J.

1980-01-01

Explores the process of horizontal differentiation by examining events leading to the establishment of 30 new departments in five universities. Two types of horizontal differentiation processes--administrative and academic--were observed and each was associated with different organizational conditions. (Author/IRT)

Measurements of differential and double-differential Drell–Yan cross sections in proton–proton collisions at √s = 8 TeV

DOE PAGES

Khachatryan, V.; Sirunyan, A. M.; Tumasyan, A.; ...

2015-04-09

Measurements of the differential and double-differential Drell–Yan cross sections in the dielectron and dimuon channels are presented. They are based on proton–proton collision data at √s = 8TeV recorded with the CMS detector at the LHC and corresponding to an integrated luminosity of 19.7fb –1. The measured inclusive cross section in the Z peak region (60–120GeV), obtained from the combination of the dielectron and dimuon channels, is 1138 ± 8 (exp) ± 25 (theo) ± 30 (lumi)\\,pb, where the statistical uncertainty is negligible. The differential cross section dσ/dm in the dilepton mass range 15–2000GeV is measured and corrected to themore » full phase space. The double-differential cross section d 2σ/dmd|y| is also measured over the mass range 20 to 1500GeV and absolute dilepton rapidity from 0 to 2.4. In addition, the ratios of the normalized differential cross sections measured at √s = 7 and 8TeV are presented. These measurements are compared to the predictions of perturbative QCD at next-to-leading and next-to-next-to-leading (NNLO) orders using various sets of parton distribution functions (PDFs). The results agree with the NNLO theoretical predictions computed with FEWZ 3.1 using the CT10 NNLO and NNPDF2.1 NNLO PDFs. Furthermore, the measured double-differential cross section and ratio of normalized differential cross sections are sufficiently precise to constrain the proton PDFs.« less

Hematopoietic Stem/Progenitor Cell Proliferation and Differentiation Is Differentially Regulated by High-Density and Low-Density Lipoproteins in Mice

PubMed Central

Feng, Yingmei; Schouteden, Sarah; Geenens, Rachel; Van Duppen, Vik; Herijgers, Paul; Holvoet, Paul; Van Veldhoven, Paul P.; Verfaillie, Catherine M.

2012-01-01

Rationale Hematopoietic stem/progenitor cells (HSPC) are responsible for maintaining the blood system as a result of their self-renewal and multilineage differentiation capacity. Recently, studies have suggested that HDL cholesterol may inhibit and impaired cholesterol efflux may increase HSPC proliferation and differentiation. Objectives We hypothesized that LDL may enhance HSPC proliferation and differentiation while HDL might have the opposing effect which might influence the size of the pool of inflammatory cells. Methods and Results HSPC number and function were studied in hypercholesterolemic LDL receptor knockout (LDLr−/−) mice on high fat diet. Hypercholesterolemia was associated with increased frequency of HSPC, monocytes and granulocytes in the peripheral blood (PB). In addition, an increased proportion of BM HSPC was in G2M of the cell cycle, and the percentage of HSPC and granulocyte-macrophage progenitors (GMP) increased in BM of LDLr−/− mice. When BM Lin-Sca-1+cKit+ (i.e. “LSK”) cells were cultured in the presence of LDL in vitro we also found enhanced differentiation towards monocytes and granulocytes. Furthermore, LDL promoted lineage negative (Lin−) cells motility. The modulation by LDL on HSPC differentiation into granulocytes and motility was inhibited by inhibiting ERK phosphorylation. By contrast, when mice were infused with human apoA-I (the major apolipoprotein of HDL) or reconstituted HDL (rHDL), the frequency and proliferation of HSPC was reduced in BM in vivo. HDL also reversed the LDL-induced monocyte and granulocyte differentiation in vitro. Conclusion Our data suggest that LDL and HDL have opposing effects on HSPC proliferation and differentiation. It will be of interest to determine if breakdown of HSPC homeostasis by hypercholesterolemia contributes to inflammation and atherosclerosis progression. PMID:23144813

Solution of differential equations by application of transformation groups

NASA Technical Reports Server (NTRS)

Driskell, C. N., Jr.; Gallaher, L. J.; Martin, R. H., Jr.

1968-01-01

Report applies transformation groups to the solution of systems of ordinary differential equations and partial differential equations. Lies theorem finds an integrating factor for appropriate invariance group or groups can be found and can be extended to partial differential equations.

Mechanical stimuli differentially control stem cell behavior: morphology, proliferation, and differentiation

PubMed Central

Maul, Timothy M.; Chew, Douglas W.; Nieponice, Alejandro

2011-01-01

Mesenchymal stem cell (MSC) therapy has demonstrated applications in vascular regenerative medicine. Although blood vessels exist in a mechanically dynamic environment, there has been no rigorous, systematic analysis of mechanical stimulation on stem cell differentiation. We hypothesize that mechanical stimuli, relevant to the vasculature, can differentiate MSCs toward smooth muscle (SMCs) and endothelial cells (ECs). This was tested using a unique experimental platform to differentially apply various mechanical stimuli in parallel. Three forces, cyclic stretch, cyclic pressure, and laminar shear stress, were applied independently to mimic several vascular physiologic conditions. Experiments were conducted using subconfluent MSCs for 5 days and demonstrated significant effects on morphology and proliferation depending upon the type, magnitude, frequency, and duration of applied stimulation. We have defined thresholds of cyclic stretch that potentiate SMC protein expression, but did not find EC protein expression under any condition tested. However, a second set of experiments performed at confluence and aimed to elicit the temporal gene expression response of a select magnitude of each stimulus revealed that EC gene expression can be increased with cyclic pressure and shear stress in a cell-contact-dependent manner. Further, these MSCs also appear to express genes from multiple lineages simultaneously which may warrant further investigation into post-transcriptional mechanisms for controlling protein expression. To our knowledge, this is the first systematic examination of the effects of mechanical stimulation on MSCs and has implications for the understanding of stem cell biology, as well as potential bioreactor designs for tissue engineering and cell therapy applications. PMID:21253809

Test of CCD Precision Limits for Differential Photometry

NASA Technical Reports Server (NTRS)

Robinson, L. B.; Wei, M. Z.; Borucki, W. J.; Dunham, E. W.; Ford, C. H.; Granados, A. F.

1995-01-01

Results of tests to demonstrate the very high differential-photometric stability of CCD light sensors are presented. The measurements reported here demonstrate that in a controlled laboratory environment, a front-illuminated CCD can provide differential-photometric measurements with reproducible precision approaching one part in 10(exp 5). Practical limitations to the precision of differential-photometric measurements with CCDs and implications for spaceborne applications are discussed.

Nystagmus as a Sign of Labyrinthine Disorders-Three-Dimensional Analysis of Nystagmus-

PubMed Central

2008-01-01

In order to diagnose the pathological condition of vertiginous patients, a detailed observation of nystagmus in addition to examination of body equilibrium and other neurotological tests are essential. How to precisely record the eye movements is one of the goals of the researchers and clinicians who are interested in the analysis of eye movements for a long time. For considering that, one has to think about the optimal method for recording eye movements. In this review, the author introduced a new method, that is, an analysis of vestibular induced eye movements in three-dimensions and discussed the advantages and limitations of this method. PMID:19434275

Changes in Differentiation-Relatedness During Psychoanalysis.

PubMed

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

2016-01-01

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

[Role of CD2-associated protein in podocyte differentiation.].

PubMed

Jiang, Hua-Jun; Chang, Ying; Zhu, Zhong-Hua; Liu, Jian-She; Deng, An-Guo; Zhang, Chun

2008-02-25

To study the cellular changes and the potential role of CD2-associated protein (CD2AP) in podocyte differentiation, conditionally immortalized murine podocyte cell line was cultured in RPMI 1640 medium under permissive condition at 33 °C. After transfection with CD2AP small interfering RNA (siRNA) the cells were shifted to non-permissive condition at 37 °C. Simultaneously, untransfected cells were taken as differentiation control. The podocyte proliferation rate was determined by MTT method. The expressions of CD2AP, WT1, synaptopodin and nephrin mRNAs were examined by RT-PCR. CD2AP, WT1 and nephrin protein expressions were examined by Western blot. The distribution of CD2AP, nephrin, F-actin and tubulin in differentiated and undifferentiated podocytes was detected by laser scanning confocal microscopy. The results showed: (1) CD2AP, WT1 and nephrin were stably expressed in differentiated and undifferentiated podocytes while synaptopodin was only expressed in differentiated podocytes. (2) CD2AP and nephrin mRNA and protein expressions were up-regulated during podocyte differentiation (P<0.05). (3) CD2AP and tubulin were distributed in the cytoplasm and perinulcear region in undifferentiated podocytes, and F-actin was predominantly localized to a cortical belt and paralleled to the cell axis. Under differentiation condition, CD2AP distribution profile was presented as peripheral accumulation, tubulin took on fascicular style and F-actin extended into foot processes in podocytes. CD2AP colocalized with nephrin and F-actin in undifferentiated podocytes. (4) After transfection with CD2AP siRNA, the expression of CD2AP was partially inhibited and cell growth was arrested; Synaptopodin, the differentiation podocyte marker, was apparently down-regulated; The differentiation of podocytes was delayed. The results demonstrate that podocyte differentiation is accompanied by cytoskeleton rearrangement and cell morphology change. CD2AP might play an essential role in podocyte

Computations involving differential operators and their actions on functions

NASA Technical Reports Server (NTRS)

Crouch, Peter E.; Grossman, Robert; Larson, Richard

1991-01-01

The algorithms derived by Grossmann and Larson (1989) are further developed for rewriting expressions involving differential operators. The differential operators involved arise in the local analysis of nonlinear dynamical systems. These algorithms are extended in two different directions: the algorithms are generalized so that they apply to differential operators on groups and the data structures and algorithms are developed to compute symbolically the action of differential operators on functions. Both of these generalizations are needed for applications.

Ordinary differential equation for local accumulation time.

PubMed

Berezhkovskii, Alexander M

2011-08-21

Cell differentiation in a developing tissue is controlled by the concentration fields of signaling molecules called morphogens. Formation of these concentration fields can be described by the reaction-diffusion mechanism in which locally produced molecules diffuse through the patterned tissue and are degraded. The formation kinetics at a given point of the patterned tissue can be characterized by the local accumulation time, defined in terms of the local relaxation function. Here, we show that this time satisfies an ordinary differential equation. Using this equation one can straightforwardly determine the local accumulation time, i.e., without preliminary calculation of the relaxation function by solving the partial differential equation, as was done in previous studies. We derive this ordinary differential equation together with the accompanying boundary conditions and demonstrate that the earlier obtained results for the local accumulation time can be recovered by solving this equation. © 2011 American Institute of Physics

Low-voltage differentially-signaled modulators.

PubMed

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

2011-12-19

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

The Chabot Emotional Differentiation Scale: A Theoretically and Psychometrically Sound Instrument for Measuring Bowen's Intrapsychic Aspect of Differentiation

ERIC Educational Resources Information Center

Licht, Carolyn; Chabot, David

2006-01-01

Bowen's theory (1978) of differentiation is the personality variable most critical to mature development and the attainment of psychological health. The study of psychological differentiation has been confounded by confusion regarding the constructs being studied and the measurement tools used to assess them. The purpose of this review is to…

Search for a Differentiated Asteroid Family

NASA Astrophysics Data System (ADS)

Thomas, Cristina A.; Lim, Lucy F.; Trilling, David E.; Moskovitz, Nicholas

2014-08-01

Dynamical asteroid families resulting from catastrophic disruptions represent the interiors of their former parent bodies. Differentiation of a large initially chondritic parent body is expected to produce an ``onion shell" object with a metal core, a thick olivine-rich mantle, and a thin basaltic crust. However, instead of the mineralogical diversity expected from the disruption of a differentiated parent body, most asteroid families tend to show similar spectra among the members. Moreover, spectra of metal-like materials and olivine-dominated assemblages have not been detected in asteroid families in the Main Belt and the expected mantle material is missing from the meteorite record. The deficit of olivine-rich mantle material in the meteorite record and in asteroid observations is known as the ``Missing Mantle" problem. For years the best explanation for the lack of mantle material has been the ``battered to bits" hypothesis that states that all differentiated parent bodies (aside from Vesta) were disrupted very early in the solar system and the resulting olivine-rich material was collisionally broken down until the object diameters fell below our observational limits. However, in a new, competing, hypothesis, Elkins-Tanton et al. (2013) has suggested that previous work has overestimated the amount of olivine produced by the differentiation of a chondritic parent body. We propose to obtain visible spectra of asteroids within the Massalia, Merxia, and Agnia S-type families to search for compositional variations that are indicators of differentiation and to quantitatively constrain the two competing ``Missing Mantle" hypotheses.

Teaching Modeling with Partial Differential Equations: Several Successful Approaches

ERIC Educational Resources Information Center

Myers, Joseph; Trubatch, David; Winkel, Brian

2008-01-01

We discuss the introduction and teaching of partial differential equations (heat and wave equations) via modeling physical phenomena, using a new approach that encompasses constructing difference equations and implementing these in a spreadsheet, numerically solving the partial differential equations using the numerical differential equation…

Navier-Stokes dynamics on a differential one-form

NASA Astrophysics Data System (ADS)

Story, Troy L.

2006-11-01

After transforming the Navier-Stokes dynamic equation into a characteristic differential one-form on an odd-dimensional differentiable manifold, exterior calculus is used to construct a pair of differential equations and tangent vector(vortex vector) characteristic of Hamiltonian geometry. A solution to the Navier-Stokes dynamic equation is then obtained by solving this pair of equations for the position x^k and the conjugate to the position bk as functions of time. The solution bk is shown to be divergence-free by contracting the differential 3-form corresponding to the divergence of the gradient of the velocity with a triple of tangent vectors, implying constraints on two of the tangent vectors for the system. Analysis of the solution bk shows it is bounded since it remains finite as | x^k | ->,, and is physically reasonable since the square of the gradient of the principal function is bounded. By contracting the characteristic differential one-form with the vortex vector, the Lagrangian is obtained.

Bit-1 is an essential regulator of myogenic differentiation

PubMed Central

Griffiths, Genevieve S.; Doe, Jinger; Jijiwa, Mayumi; Van Ry, Pam; Cruz, Vivian; de la Vega, Michelle; Ramos, Joe W.; Burkin, Dean J.; Matter, Michelle L.

2015-01-01

Muscle differentiation requires a complex signaling cascade that leads to the production of multinucleated myofibers. Genes regulating the intrinsic mitochondrial apoptotic pathway also function in controlling cell differentiation. How such signaling pathways are regulated during differentiation is not fully understood. Bit-1 (also known as PTRH2) mutations in humans cause infantile-onset multisystem disease with muscle weakness. We demonstrate here that Bit-1 controls skeletal myogenesis through a caspase-mediated signaling pathway. Bit-1-null mice exhibit a myopathy with hypotrophic myofibers. Bit-1-null myoblasts prematurely express muscle-specific proteins. Similarly, knockdown of Bit-1 expression in C2C12 myoblasts promotes early differentiation, whereas overexpression delays differentiation. In wild-type mice, Bit-1 levels increase during differentiation. Bit-1-null myoblasts exhibited increased levels of caspase 9 and caspase 3 without increased apoptosis. Bit-1 re-expression partially rescued differentiation. In Bit-1-null muscle, Bcl-2 levels are reduced, suggesting that Bcl-2-mediated inhibition of caspase 9 and caspase 3 is decreased. Bcl-2 re-expression rescued Bit-1-mediated early differentiation in Bit-1-null myoblasts and C2C12 cells with knockdown of Bit-1 expression. These results support an unanticipated yet essential role for Bit-1 in controlling myogenesis through regulation of Bcl-2. PMID:25770104

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

Differential correlation for sequencing data.

PubMed

Siska, Charlotte; Kechris, Katerina

2017-01-19

Several methods have been developed to identify differential correlation (DC) between pairs of molecular features from -omics studies. Most DC methods have only been tested with microarrays and other platforms producing continuous and Gaussian-like data. Sequencing data is in the form of counts, often modeled with a negative binomial distribution making it difficult to apply standard correlation metrics. We have developed an R package for identifying DC called Discordant which uses mixture models for correlations between features and the Expectation Maximization (EM) algorithm for fitting parameters of the mixture model. Several correlation metrics for sequencing data are provided and tested using simulations. Other extensions in the Discordant package include additional modeling for different types of differential correlation, and faster implementation, using a subsampling routine to reduce run-time and address the assumption of independence between molecular feature pairs. With simulations and breast cancer miRNA-Seq and RNA-Seq data, we find that Spearman's correlation has the best performance among the tested correlation methods for identifying differential correlation. Application of Spearman's correlation in the Discordant method demonstrated the most power in ROC curves and sensitivity/specificity plots, and improved ability to identify experimentally validated breast cancer miRNA. We also considered including additional types of differential correlation, which showed a slight reduction in power due to the additional parameters that need to be estimated, but more versatility in applications. Finally, subsampling within the EM algorithm considerably decreased run-time with negligible effect on performance. A new method and R package called Discordant is presented for identifying differential correlation with sequencing data. Based on comparisons with different correlation metrics, this study suggests Spearman's correlation is appropriate for sequencing data

Identifying microRNAs that Regulate Neuroblastoma Cell Differentiation

DTIC Science & Technology

2015-10-01

Award Number: W81XWH-13-1-0241 TITLE: Identifying that Regulate Neuroblastoma Cell Differentiation PRINCIPAL INVESTIGATOR: Dr. Liqin Du...inducing miRNA, miR- 449a. We examined the differentiation-inducing function of miR-449a in multiple neuroblastoma cell lines. We have demonstrated that...miR-449a functions as an inducer of cell differentiation in neuroblastoma cell lines with distinct genetic backgrounds, including the MYCN

Schwarz maps of algebraic linear ordinary differential equations

NASA Astrophysics Data System (ADS)

Sanabria Malagón, Camilo

2017-12-01

A linear ordinary differential equation is called algebraic if all its solution are algebraic over its field of definition. In this paper we solve the problem of finding closed form solution to algebraic linear ordinary differential equations in terms of standard equations. Furthermore, we obtain a method to compute all algebraic linear ordinary differential equations with rational coefficients by studying their associated Schwarz map through the Picard-Vessiot Theory.

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…

Reconcilable Differences: Standards-based Teaching and Differentiation.

ERIC Educational Resources Information Center

Tomlinson, Carol Ann

2000-01-01

There is no contradiction between effective standards-based instruction and differentiation. Curriculum tells teachers what to teach; differentiation tells how. Teachers can challenge all learners by providing standards-based materials and tasks calling for varied difficulty levels, scaffolding, instructional styles, and learning times. (MLH)

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…

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis

PubMed Central

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

2016-01-01

In the stationary phase, Bacillus subtilis differentiates stochastically and transiently into the state of competence for transformation (K-state). The latter is associated with growth arrest, and it is unclear how the ability to develop competence is stably maintained, despite its cost. To quantify the effect differentiation has on the competitive fitness of B. subtilis, we characterized the competition dynamics between strains with different probabilities of entering the K-state. The relative fitness decreased with increasing differentiation probability both during the stationary phase and during outgrowth. When exposed to antibiotics inhibiting cell wall synthesis, transcription, and translation, cells that differentiated into the K-state showed a selective advantage compared to differentiation-deficient bacteria; this benefit did not require transformation. Although beneficial, the K-state was not induced by sub-MIC concentrations of antibiotics. Increasing the differentiation probability beyond the wt level did not significantly affect the competition dynamics with transient antibiotic exposure. We conclude that the competition dynamics are very sensitive to the fraction of competent cells under benign conditions but less sensitive during antibiotic exposure, supporting the picture of stochastic differentiation as a fitness trade-off. PMID:27375604

Fitness Trade-Offs in Competence Differentiation of Bacillus subtilis.

PubMed

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

2016-01-01

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

Chromatin in embryonic stem cell neuronal differentiation.

PubMed

Meshorer, E

2007-03-01

Chromatin, the basic regulatory unit of the eukaryotic genetic material, is controlled by epigenetic mechanisms including histone modifications, histone variants, DNA methylation and chromatin remodeling. Cellular differentiation involves large changes in gene expression concomitant with alterations in genome organization and chromatin structure. Such changes are particularly evident in self-renewing pluripotent embryonic stem cells, which begin, in terms of cell fate, as a tabula rasa, and through the process of differentiation, acquire distinct identities. Here I describe the changes in chromatin that accompany neuronal differentiation, particularly of embryonic stem cells, and discuss how chromatin serves as the master regulator of cellular destiny.

Improving X-Ray Optics via Differential Deposition

NASA Technical Reports Server (NTRS)

Kilaru, Kiranmayee; Ramsey, Brian D.; Atkins, Carolyn

2017-01-01

Differential deposition, a post-fabrication figure correction technique, has the potential to significantly improve the imaging quality of grazing-incidence X-ray optics. DC magnetron sputtering is used to selectively coat the mirror in order to minimize the figure deviations. Custom vacuum chambers have been developed at NASA MSFC that will enable the implementation of the deposition on X-ray optics. A factor of two improvement has been achieved in the angular resolution of the full-shell X-ray optics with first stage correction of differential deposition. Current efforts are focused on achieving higher improvements through efficient implementation of differential deposition.

Differential levels of Neurod establish zebrafish endocrine pancreas cell fates

PubMed Central

Dalgin, Gökhan; Prince, Victoria E.

2015-01-01

During development a network of transcription factors functions to differentiate foregut cells into pancreatic endocrine cells. Differentiation of appropriate numbers of each hormone-expressing endocrine cell type is essential for the normal development of the pancreas and ultimately for effective maintenance of blood glucose levels. A fuller understanding of the details of endocrine cell differentiation may contribute to development of cell replacement therapies to treat diabetes. In this study, by using morpholino and gRNA/Cas9 mediated knockdown we establish that differential levels of the basic-helix loop helix (bHLH) transcription factor Neurod are required for the differentiation of distinct endocrine cell types in developing zebrafish. While Neurod plays a role in the differentiation of all endocrine cells, we find that differentiation of glucagon-expressing alpha cells is disrupted by a minor reduction in Neurod levels, whereas differentiation of insulin-expressing beta cells is less sensitive to Neurod depletion. The endocrine cells that arise during embryonic stages to produce the primary islet, and those that arise subsequently during larval stages from the intra-pancreatic duct (IPD) to ultimately contribute to the secondary islets, show similar dependence on differential Neurod levels. Intriguingly, Neurod-deficiency triggers premature formation of endocrine precursors from the IPD during early larval stages. However, the Neurod-deficient endocrine precursors fail to differentiate appropriately, and the larvae are unable to maintain normal glucose levels. In summary, differential levels of Neurod are required to generate endocrine pancreas subtypes from precursors during both embryonic and larval stages, and Neurod function is in turn critical to endocrine function. PMID:25797153

[Differential chronic hepatitis diagnosis].

PubMed

Hinterberger, W

2000-01-01

Chronic hepatitis comprises a group of disorders of the liver exhibiting a chronic necroinflammatory process that differs in etiology, clinical course and treatment strategies. A diagnosis of chronic hepatitis is usually made when inflammation and liver cell necrosis persist for longer than 6 months. Clinical manifestations range from asymptomatic patients to those with advanced hepatic failure. Both sexes and all age groups are affected. Chronic hepatitis may emerge as a sequelae of hepatitis C and less often after hepatitis B. Both diseases are treatable and require rapid and exact diagnosis. The differential diagnosis must exclude autoimmune hepatitis, chronic steatohepatitis, congenital metabolic hepatopathies and drug-induced hepatopathies. Laboratory tests, histologic investigations and clinical differential diagnosis must exclude other causes of chronic liver disease.

Differential Resonant Ring YIG Tuned Oscillator

NASA Technical Reports Server (NTRS)

Parrott, Ronald A.

2010-01-01

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

Evidence that differentiation-inducing factor-1 controls chemotaxis and cell differentiation, at least in part, via mitochondria in D. discoideum.

PubMed

Kubohara, Yuzuru; Kikuchi, Haruhisa; Nguyen, Van Hai; Kuwayama, Hidekazu; Oshima, Yoshiteru

2017-06-15

Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m -chlorophenylhydrazone (CCCP), at 25-50 nM, and dinitrophenol (DNP), at 2.5-5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1-2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity. © 2017. Published by The Company of Biologists Ltd.

Evidence that differentiation-inducing factor-1 controls chemotaxis and cell differentiation, at least in part, via mitochondria in D. discoideum

PubMed Central

Kikuchi, Haruhisa; Nguyen, Van Hai; Kuwayama, Hidekazu; Oshima, Yoshiteru

2017-01-01

ABSTRACT Differentiation-inducing factor-1 [1-(3,5-dichloro-2,6-dihydroxy-4-methoxyphenyl)hexan-1-one (DIF-1)] is an important regulator of cell differentiation and chemotaxis in the development of the cellular slime mold Dictyostelium discoideum. However, the entire signaling pathways downstream of DIF-1 remain to be elucidated. To characterize DIF-1 and its potential receptor(s), we synthesized two fluorescent derivatives of DIF-1, boron-dipyrromethene (BODIPY)-conjugated DIF-1 (DIF-1-BODIPY) and nitrobenzoxadiazole (NBD)-conjugated DIF-1 (DIF-1-NBD), and investigated their biological activities and cellular localization. DIF-1-BODIPY (5 µM) and DIF-1 (2 nM) induced stalk cell differentiation in the DIF-deficient strain HM44 in the presence of cyclic adenosine monosphosphate (cAMP), whereas DIF-1-NBD (5 µM) hardly induced stalk cell differentiation under the same conditions. Microscopic analyses revealed that the biologically active derivative, DIF-1-BODIPY, was incorporated by stalk cells at late stages of differentiation and was localized to mitochondria. The mitochondrial uncouplers carbonyl cyanide m-chlorophenylhydrazone (CCCP), at 25–50 nM, and dinitrophenol (DNP), at 2.5–5 µM, induced partial stalk cell differentiation in HM44 in the presence of cAMP. DIF-1-BODIPY (1–2 µM) and DIF-1 (10 nM), as well as CCCP and DNP, suppressed chemotaxis in the wild-type strain Ax2 in shallow cAMP gradients. These results suggest that DIF-1-BODIPY and DIF-1 induce stalk cell differentiation and modulate chemotaxis, at least in part, by disturbing mitochondrial activity. PMID:28619991

The role of parental personality traits in differential parenting.

PubMed

Browne, Dillon T; Meunier, Jean Christophe; O'Connor, Thomas G; Jenkins, Jennifer M

2012-08-01

Significant relationships have been demonstrated between parental personality and parenting toward individual children, but there is little research exploring the relationship between parental personality and differential parenting (DP). The present study examined the relationship between the Big Five personality dimensions and differential positivity and negativity in parenting (observed and self-report measures). The analyses are based on a sample of 867 children nested within 381 families. Using multilevel modeling and controlling for child age, gender, birth order, behavior, and family socioeconomic status analyses revealed that maternal and paternal agreeableness were inversely related to reports of differential positivity. Agreeableness predicted observed differential negativity, and the relationship was curvilinear (at both high and low levels of agreeableness, differential negativity was higher). Finally, mothers with the most openness to experience exhibited the highest levels of reported differential negativity. The findings suggest that parental personality is a modest yet important influence to consider when conceptualizing the sources of DP. PsycINFO Database Record (c) 2012 APA, all rights reserved.

21 CFR 866.2320 - Differential culture medium.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Differential culture medium. 866.2320 Section 866.2320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2320 Differential culture...

21 CFR 866.2320 - Differential culture medium.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Differential culture medium. 866.2320 Section 866.2320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2320 Differential culture...

21 CFR 866.2320 - Differential culture medium.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Differential culture medium. 866.2320 Section 866.2320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2320 Differential culture...

21 CFR 866.2320 - Differential culture medium.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Differential culture medium. 866.2320 Section 866.2320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2320 Differential culture...

21 CFR 866.2320 - Differential culture medium.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Differential culture medium. 866.2320 Section 866.2320 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Microbiology Devices § 866.2320 Differential culture...

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.

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.

The existence of solutions of q-difference-differential equations.

PubMed

Wang, Xin-Li; Wang, Hua; Xu, Hong-Yan

2016-01-01

By using the Nevanlinna theory of value distribution, we investigate the existence of solutions of some types of non-linear q-difference differential equations. In particular, we generalize the Rellich-Wittich-type theorem and Malmquist-type theorem about differential equations to the case of q-difference differential equations (system).

Deregulated proliferation and differentiation in brain tumors

PubMed Central

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

2014-01-01

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

Partitioning-based mechanisms under personalized differential privacy.

PubMed

Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

2017-05-01

Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t -round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms.

Partitioning-based mechanisms under personalized differential privacy

PubMed Central

Li, Haoran; Xiong, Li; Ji, Zhanglong; Jiang, Xiaoqian

2017-01-01

Differential privacy has recently emerged in private statistical aggregate analysis as one of the strongest privacy guarantees. A limitation of the model is that it provides the same privacy protection for all individuals in the database. However, it is common that data owners may have different privacy preferences for their data. Consequently, a global differential privacy parameter may provide excessive privacy protection for some users, while insufficient for others. In this paper, we propose two partitioning-based mechanisms, privacy-aware and utility-based partitioning, to handle personalized differential privacy parameters for each individual in a dataset while maximizing utility of the differentially private computation. The privacy-aware partitioning is to minimize the privacy budget waste, while utility-based partitioning is to maximize the utility for a given aggregate analysis. We also develop a t-round partitioning to take full advantage of remaining privacy budgets. Extensive experiments using real datasets show the effectiveness of our partitioning mechanisms. PMID:28932827

The Hippo pathway regulates human megakaryocytic differentiation.

PubMed

Lorthongpanich, Chanchao; Jiamvoraphong, Nittaya; Supraditaporn, Kantpitchar; Klaihmon, Phatchanat; U-Pratya, Yaowalak; Issaragrisil, Surapol

2017-01-05

The Hippo pathway is involved in several biological processes in both flies and mammals. Recent studies have shown that the Hippo pathway regulates Drosophila's haematopoiesis; however, understanding of its role in mammalian haematopoiesis is still limited. In flies, deletion of the Hippo component gene, Warts, affects crystal cell differentiation. We explored the role of the Hippo pathway in human haematopoiesis focusing on megakaryopoiesis. To investigate the role of LATS1/2 (a mammalian homolog of Warts) in human megakaryoblastic cell differentiation and platelet formation, megakaryoblastic cell (MEG-01) line was used as a model to gain insight into mechanism of the Hippo pathway in mammalian megakaryopoiesis. Effect of LATS1/2 on megakaryoblastic cell differentiation and platelet production were determined by functional changes. We found that depletion of LATS1/2 resulted in an increase of CD41 + megakaryocytes with impaired platelet biogenesis. Our study shows that the Hippo signalling pathway plays a crucial role in human megakaryoblastic cell differentiation and thrombopoiesis.

Role of thrombopoietin in mast cell differentiation.

PubMed

Migliaccio, Anna Rita; Rana, Rosa Alba; Vannucchi, Alessandro M; Manzoli, Francesco A

2007-06-01

Mast cells are important elements of the body response to foreign antigens, being those represented either by small molecules (allergic response) or harbored by foreign microorganisms (response to parasite infection). These cells derive from hematopoietic stem/progenitor cells present in the marrow. However, in contrast with most of the other hematopoietic lineages, mast cells do not differentiate in the marrow but in highly vascularized extramedullary sites, such as the skin or the gut. Mast cell differentiation in the marrow is activated as part of the body response to parasites. We will review here the mast cell differentiation pathway and what is known of its major intrinsic and extrinsic control mechanisms. It will also be described that thrombopoietin, the ligand for the Mpl receptor, in addition to its pivotal rule in the control of thrombocytopoiesis and of hematopoietic stem/progenitor cell proliferation, exerts a regulatory function in mast cell differentiation. Some of the possible implications of this newly described biological activity of thrombopoietin will be discussed.

Differential GPS/inertial navigation approach/landing flight test results

NASA Technical Reports Server (NTRS)

Snyder, Scott; Schipper, Brian; Vallot, Larry; Parker, Nigel; Spitzer, Cary

1992-01-01

In November of 1990 a joint Honeywell/NASA-Langley differential GPS/inertial flight test was conducted at Wallops Island, Virginia. The test objective was to acquire a system performance database and demonstrate automatic landing using an integrated differential GPS/INS (Global Positioning System/inertial navigation system) with barometric and radar altimeters. The flight test effort exceeded program objectives with over 120 landings, 36 of which were fully automatic differential GPS/inertial landings. Flight test results obtained from post-flight data analysis are discussed. These results include characteristics of differential GPS/inertial error, using the Wallops Island Laser Tracker as a reference. Data on the magnitude of the differential corrections and vertical channel performance with and without radar altimeter augmentation are provided.

Laser-ranging long-baseline differential atom interferometers for space

NASA Astrophysics Data System (ADS)

Chiow, Sheng-wey; Williams, Jason; Yu, Nan

2015-12-01

High-sensitivity differential atom interferometers (AIs) are promising for precision measurements in science frontiers in space, including gravity-field mapping for Earth science studies and gravitational wave detection. Difficulties associated with implementing long-baseline differential AIs have previously included the need for a high optical power, large differential Doppler shifts, and narrow dynamic range. We propose a configuration of twin AIs connected by a laser-ranging interferometer (LRI-AI) to provide precise information of the displacements between the two AI reference mirrors and also to phase-lock the two independent interferometer lasers over long distances, thereby drastically improving the practical feasibility of long-baseline differential AI measurements. We show that a properly implemented LRI-AI can achieve equivalent functionality to the conventional differential AI measurement configuration.

Superconductive microstrip exhibiting negative differential resistivity

DOEpatents

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

1975-10-28

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

Integrator complex plays an essential role in adipose differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Otani, Yuichiro; Nakatsu, Yusuke; Sakoda, Hideyuki

2013-05-03

Highlights: •IntS6 and IntS11 are subunits of the Integrator complex. •Expression levels of IntS6 and IntS11 were very low in 3T3-L1 fibroblast. •IntS6 and IntS11 were upregulated during adipose differentiation. •Suppression of IntS6 or IntS11 expression inhibited adipose differentiation. -- Abstract: The dynamic process of adipose differentiation involves stepwise expressions of transcription factors and proteins specific to the mature fat cell phenotype. In this study, it was revealed that expression levels of IntS6 and IntS11, subunits of the Integrator complex, were increased in 3T3-L1 cells in the period when the cells reached confluence and differentiated into adipocytes, while being reducedmore » to basal levels after the completion of differentiation. Suppression of IntS6 or IntS11 expression using siRNAs in 3T3-L1 preadipocytes markedly inhibited differentiation into mature adipocytes, based on morphological findings as well as mRNA analysis of adipocyte-specific genes such as Glut4, perilipin and Fabp4. Although Pparγ2 protein expression was suppressed in IntS6 or IntS11-siRNA treated cells, adenoviral forced expression of Pparγ2 failed to restore the capacity for differentiation into mature adipocytes. Taken together, these findings demonstrate that increased expression of Integrator complex subunits is an indispensable event in adipose differentiation. Although further study is necessary to elucidate the underlying mechanism, the processing of U1, U2 small nuclear RNAs may be involved in cell differentiation steps.« less

Differential porosimetry and permeametry for random porous media.

PubMed

Hilfer, R; Lemmer, A

2015-07-01

Accurate determination of geometrical and physical properties of natural porous materials is notoriously difficult. Continuum multiscale modeling has provided carefully calibrated realistic microstructure models of reservoir rocks with floating point accuracy. Previous measurements using synthetic microcomputed tomography (μ-CT) were based on extrapolation of resolution-dependent properties for discrete digitized approximations of the continuum microstructure. This paper reports continuum measurements of volume and specific surface with full floating point precision. It also corrects an incomplete description of rotations in earlier publications. More importantly, the methods of differential permeametry and differential porosimetry are introduced as precision tools. The continuum microstructure chosen to exemplify the methods is a homogeneous, carefully calibrated and characterized model for Fontainebleau sandstone. The sample has been publicly available since 2010 on the worldwide web as a benchmark for methodical studies of correlated random media. High-precision porosimetry gives the volume and internal surface area of the sample with floating point accuracy. Continuum results with floating point precision are compared to discrete approximations. Differential porosities and differential surface area densities allow geometrical fluctuations to be discriminated from discretization effects and numerical noise. Differential porosimetry and Fourier analysis reveal subtle periodic correlations. The findings uncover small oscillatory correlations with a period of roughly 850μm, thus implying that the sample is not strictly stationary. The correlations are attributed to the deposition algorithm that was used to ensure the grain overlap constraint. Differential permeabilities are introduced and studied. Differential porosities and permeabilities provide scale-dependent information on geometry fluctuations, thereby allowing quantitative error estimates.

A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

PubMed

Annibali, Daniela; Gioia, Ubaldo; Savino, Mauro; Laneve, Pietro; Caffarelli, Elisa; Nasi, Sergio

2012-01-01

The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

Survival and differentiation defects contribute to neutropenia in glucose-6-phosphatase-β (G6PC3) deficiency in a model of mouse neutrophil granulocyte differentiation.

PubMed

Gautam, S; Kirschnek, S; Gentle, I E; Kopiniok, C; Henneke, P; Häcker, H; Malleret, L; Belaaouaj, A; Häcker, G

2013-08-01

Differentiation of neutrophil granulocytes (neutrophils) occurs through several steps in the bone marrow and requires a coordinate regulation of factors determining survival and lineage-specific development. A number of genes are known whose deficiency disrupts neutrophil generation in humans and in mice. One of the proteins encoded by these genes, glucose-6-phosphatase-β (G6PC3), is involved in glucose metabolism. G6PC3 deficiency causes neutropenia in humans and in mice, linked to enhanced apoptosis and ER stress. We used a model of conditional Hoxb8 expression to test molecular and functional differentiation as well as survival defects in neutrophils from G6PC3(-/-) mice. Progenitor lines were established and differentiated into neutrophils when Hoxb8 was turned off. G6PC3(-/-) progenitor cells underwent substantial apoptosis when differentiation was started. Transgenic expression of Bcl-XL rescued survival; however, Bcl-XL-protected differentiated cells showed reduced proliferation, immaturity and functional deficiency such as altered MAP kinase signaling and reduced cytokine secretion. Impaired glucose utilization was found and was associated with ER stress and apoptosis, associated with the upregulation of Bim and Bax; downregulation of Bim protected against apoptosis during differentiation. ER-stress further caused a profound loss of expression and secretion of the main neutrophil product neutrophil elastase during differentiation. Transplantation of wild-type Hoxb8-progenitor cells into irradiated mice allowed differentiation into neutrophils in the bone marrow in vivo. Transplantation of G6PC3(-/-) cells yielded few mature neutrophils in bone marrow and peripheral blood. Transgenic Bcl-XL permitted differentiation of G6PC3(-/-) cells in vivo. However, functional deficiencies and differentiation abnormalities remained. Differentiation of macrophages from Hoxb8-dependent progenitors was only slightly disturbed. A combination of defects in differentiation

Modeling Ability Differentiation in the Second-Order Factor Model

ERIC Educational Resources Information Center

Molenaar, Dylan; Dolan, Conor V.; van der Maas, Han L. J.

2011-01-01

In this article we present factor models to test for ability differentiation. Ability differentiation predicts that the size of IQ subtest correlations decreases as a function of the general intelligence factor. In the Schmid-Leiman decomposition of the second-order factor model, we model differentiation by introducing heteroscedastic residuals,…

12 CFR 619.9130 - Differential interest rates.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Differential interest rates. 619.9130 Section 619.9130 Banks and Banking FARM CREDIT ADMINISTRATION FARM CREDIT SYSTEM DEFINITIONS § 619.9130 Differential interest rates. An interest rate program under which different rates of interest may be made...

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…

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.)

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…

Variable-mesh method of solving differential equations

NASA Technical Reports Server (NTRS)

Van Wyk, R.

1969-01-01

Multistep predictor-corrector method for numerical solution of ordinary differential equations retains high local accuracy and convergence properties. In addition, the method was developed in a form conducive to the generation of effective criteria for the selection of subsequent step sizes in step-by-step solution of differential equations.

[Thyroid carcinoma--differentiated, poorly differentiated and anaplastic carcinoma].

PubMed

Kakudo, Kennichi; Bai, Yanhua; Li, Yaqiong; Wakasa, Tomoko; Mori, Ichiro

2007-11-01

The poorly differentiated carcinoma was first added as a new member in the lists of classification of thyroid carcinomas in the WHO 2004 edition. However its histological criteria include necrosis and increased mitoses in addition to the original definition by Sakamoto's proposal, solid, trabecular and schirrhous growth. This modification creates a significant change in the incidence and prognosis of this carcinoma. This carcinoma, defined by the new WHO classification, is about 1-5% of all thyroid malignancy and has more aggressive outcome than the previous definition.

Melanosome uptake is associated with the proliferation and differentiation of keratinocytes.

PubMed

Choi, Hye-In; Sohn, Kyung-Cheol; Hong, Dong-Kyun; Lee, Young; Kim, Chang Deok; Yoon, Tae-Jin; Park, Jin Woon; Jung, Sunggyun; Lee, Jeung-Hoon; Lee, Young Ho

2014-01-01

Melanosomes are synthesized in melanocytes and transferred to neighboring keratinocytes. However, the associations of melanosome uptake with the proliferation and differentiation of keratinocytes are not fully understood. We examined the associations of melanosome uptake with keratinocyte differentiation and proliferation. SV40T-transformed human epidermal keratinocytes (SV-HEKs) were treated with isolated melanosomes. The effects of melanosome uptake on the proliferation and differentiation of the keratinocytes were analyzed by Western blotting and flow cytometry. The relationship between melanosome uptake and keratinocyte differentiation status was verified by determining the melanin content in the cells. Melanosomes reduced the proliferation of SV-HEKs in a dose-dependent manner, but did not induce differentiation. Melanosome uptake was higher in differentiating keratinocytes compared to non-differentiating keratinocytes, and inhibited significantly by PAR-2 inhibitor. Melanosomes inhibit keratinocyte proliferation. Moreover, melanosome uptake is influenced by keratinocyte differentiation status, being highest in mid-stage differentiating keratinocytes in a PAR-2 dependent manner.

Numerical methods for stochastic differential equations

NASA Astrophysics Data System (ADS)

Kloeden, Peter; Platen, Eckhard

1991-06-01

The numerical analysis of stochastic differential equations differs significantly from that of ordinary differential equations due to the peculiarities of stochastic calculus. This book provides an introduction to stochastic calculus and stochastic differential equations, both theory and applications. The main emphasise is placed on the numerical methods needed to solve such equations. It assumes an undergraduate background in mathematical methods typical of engineers and physicists, through many chapters begin with a descriptive summary which may be accessible to others who only require numerical recipes. To help the reader develop an intuitive understanding of the underlying mathematicals and hand-on numerical skills exercises and over 100 PC Exercises (PC-personal computer) are included. The stochastic Taylor expansion provides the key tool for the systematic derivation and investigation of discrete time numerical methods for stochastic differential equations. The book presents many new results on higher order methods for strong sample path approximations and for weak functional approximations, including implicit, predictor-corrector, extrapolation and variance-reduction methods. Besides serving as a basic text on such methods. the book offers the reader ready access to a large number of potential research problems in a field that is just beginning to expand rapidly and is widely applicable.

Glial tumors with neuronal differentiation.

PubMed

Park, Chul-Kee; Phi, Ji Hoon; Park, Sung-Hye

2015-01-01

Immunohistochemical studies for neuronal differentiation in glial tumors revealed subsets of tumors having both characteristics of glial and neuronal lineages. Glial tumors with neuronal differentiation can be observed with diverse phenotypes and histologic grades. The rosette-forming glioneuronal tumor of the fourth ventricle and papillary glioneuronal tumor have been newly classified as distinct disease entities. There are other candidates for classification, such as the glioneuronal tumor without pseudopapillary architecture, glioneuronal tumor with neuropil-like islands, and the malignant glioneuronal tumor. The clinical significance of these previously unclassified tumors should be confirmed. Copyright © 2015 Elsevier Inc. All rights reserved.

Fedosov differentials and Catalan numbers

NASA Astrophysics Data System (ADS)

Löffler, Johannes

2010-06-01

The aim of the paper is to establish a non-recursive formula for the general solution of Fedosov's 'quadratic' fixed-point equation (Fedosov 1994 J. Diff. Geom. 40 213-38). Fedosov's geometrical fixed-point equation for a differential is rewritten in a form similar to the functional equation for the generating function of Catalan numbers. This allows us to guess the solution. An adapted example for Kaehler manifolds of constant sectional curvature is considered in detail. Also for every connection on a manifold a familiar classical differential will be introduced. Dedicated to the memory of Nikolai Neumaier.

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…

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…

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.

Adipocyte induction of preadipocyte differentiation in a gradient chamber.

PubMed

Lai, Ning; Sims, James K; Jeon, Noo Li; Lee, Kyongbum

2012-12-01

Adipose tissue expansion involves enlargement of mature adipocytes and the formation of new adipocytes through the differentiation of locally resident preadipocytes. Factors released by the enlarged adipocytes are potential cues that induce the differentiation of the preadipocytes. Currently, there are limited options to investigate these cues in isolation from confounding systemic influences. A gradient generating microfluidic channel-based cell culture system was designed to enable solution patterning, while supporting long-term culture and differentiation of preadipocytes. Solution patterning was confirmed by selectively staining a fraction of uniformly seeded preadipocytes. An adipogenic cocktail gradient was used to induce the differentiation of a fraction of uniformly seeded preadipocytes and establish a spatially defined coculture of adipocytes and preadipocytes. Varying the adipogenic cocktail gradient generated cocultures of preadipocytes and adipocytes with different compositions. Transient application of the cocktail gradient, followed by basal medium treatment showed a biphasic induction of differentiation. The two phases of differentiation correlated with a spatial gradient in adipocyte size. Our results provide in vitro data supporting the size-dependent release of preadipocyte differentiation factors by enlarged adipocytes. Prospectively, the coculture system developed in this study could facilitate controlled, yet physiologically meaningful studies on paracrine interactions between adipocytes and preadipocytes during adipose tissue development.

7 CFR 1126.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1126.51 Section 1126.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Class Prices § 1126.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1131.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1131.51 Section 1131.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Class Prices § 1131.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1126.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1126.51 Section 1126.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE SOUTHWEST MARKETING AREA Order Regulating Handling Class Prices § 1126.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1033.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1033.51 Section 1033.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Class Prices § 1033.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1030.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1030.51 Section 1030.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Class Prices § 1030.51 Class I differential and price. The Class I differential shall be...

7 CFR 1001.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1001.51 Section 1001.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Class Prices § 1001.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1030.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1030.51 Section 1030.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE UPPER MIDWEST MARKETING AREA Order Regulating Handling Class Prices § 1030.51 Class I differential and price. The Class I differential shall be...

7 CFR 1124.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1124.51 Section 1124.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Class Prices § 1124.51 Class I differential and price. The Class I differential shall be...

7 CFR 1032.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1032.51 Section 1032.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Class Prices § 1032.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1033.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1033.51 Section 1033.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE MIDEAST MARKETING AREA Order Regulating Handling Class Prices § 1033.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1032.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1032.51 Section 1032.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE CENTRAL MARKETING AREA Order Regulating Handling Class Prices § 1032.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1131.51 - Class I differential and price.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 9 2014-01-01 2013-01-01 true Class I differential and price. 1131.51 Section 1131.51... AGREEMENTS AND ORDERS; MILK), DEPARTMENT OF AGRICULTURE MILK IN THE ARIZONA MARKETING AREA Order Regulating Handling Class Prices § 1131.51 Class I differential and price. The Class I differential shall be the...

7 CFR 1124.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1124.51 Section 1124.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE PACIFIC NORTHWEST MARKETING AREA Order Regulating Handling Class Prices § 1124.51 Class I differential and price. The Class I differential shall be...

7 CFR 1001.51 - Class I differential and price.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 9 2010-01-01 2009-01-01 true Class I differential and price. 1001.51 Section 1001.51... Agreements and Orders; Milk), DEPARTMENT OF AGRICULTURE MILK IN THE NORTHEAST MARKETING AREA Order Regulating Handling Class Prices § 1001.51 Class I differential and price. The Class I differential shall be the...

Epidermal Notch signalling: differentiation, cancer and adhesion.

PubMed

Watt, Fiona M; Estrach, Soline; Ambler, Carrie A

2008-04-01

The Notch pathway plays an important role in regulating epidermal differentiation. Notch ligands, receptors and effectors are expressed in a complex and dynamic pattern in embryonic and adult skin. Genetic ablation or activation of the pathway reveals that Notch signalling promotes differentiation of the hair follicle, sebaceous gland and interfollicular epidermal lineages and that Notch acts as an epidermal tumour suppressor. Notch signalling interacts with a range of other pathways to fulfil these functions and acts via RBP-Jkappa dependent and independent mechanisms. The effects on differentiation can be cell autonomous and non-autonomous, and Notch contributes to stem cell clustering via modulation of cell adhesion.

The cochlea in skull base surgery: an anatomy study.

PubMed

Wang, Jian; Yoshioka, Fumitaka; Joo, Wonil; Komune, Noritaka; Quilis-Quesada, Vicent; Rhoton, Albert L

2016-11-01

OBJECTIVE The object of this study was to examine the relationships of the cochlea as a guide for avoiding both cochlear damage with loss of hearing in middle fossa approaches and injury to adjacent structures in approaches directed through the cochlea. METHODS Twenty adult cadaveric middle fossae were examined using magnifications of ×3 to ×40. RESULTS The cochlea sits below the floor of the middle fossa in the area between and below the labyrinthine segment of the facial nerve and greater petrosal nerve (GPN) and adjacent to the lateral genu of the petrous carotid. Approximately one-third of the cochlea extends below the medial edge of the labyrinthine segment of the facial nerve, geniculate ganglion, and proximal part of the GPN. The medial part of the basal and middle turns are the parts at greatest risk in drilling the floor of the middle fossa to expose the nerves in middle fossa approaches to the internal acoustic meatus and in anterior petrosectomy approaches. Resection of the cochlea is used selectively in extending approaches through the mastoid toward the lateral edge of the clivus and front of the brainstem. CONCLUSIONS An understanding of the location and relationships of the cochlea will reduce the likelihood of cochlear damage with hearing loss in approaches directed through the middle fossa and reduce the incidence of injury to adjacent structures in approaches directed through the cochlea.

Adaptive plasticity in vestibular influences on cardiovascular control

NASA Technical Reports Server (NTRS)

Yates, B. J.; Holmes, M. J.; Jian, B. J.

2000-01-01

Data collected in both human subjects and animal models indicate that the vestibular system influences the control of blood pressure. In animals, peripheral vestibular lesions diminish the capacity to rapidly and accurately make cardiovascular adjustments to changes in posture. Thus, one role of vestibulo-cardiovascular influences is to elicit changes in blood distribution in the body so that stable blood pressure is maintained during movement. However, deficits in correcting blood pressure following vestibular lesions diminish over time, and are less severe when non-labyrinthine sensory cues regarding body position in space are provided. These observations show that pathways that mediate vestibulo-sympathetic reflexes can be subject to plastic changes. This review considers the adaptive plasticity in cardiovascular responses elicited by the central vestibular system. Recent data indicate that the posterior cerebellar vermis may play an important role in adaptation of these responses, such that ablation of the posterior vermis impairs recovery of orthostatic tolerance following subsequent vestibular lesions. Furthermore, recent experiments suggest that non-labyrinthine inputs to the central vestibular system may be important in controlling blood pressure during movement, particularly following vestibular dysfunction. A number of sensory inputs appear to be integrated to produce cardiovascular adjustments during changes in posture. Although loss of any one of these inputs does not induce lability in blood pressure, it is likely that maximal blood pressure stability is achieved by the integration of a variety of sensory cues signaling body position in space.

Conservation of placentation during the tertiary radiation of mammals in South America.

PubMed

Carter, Anthony Michael; Mess, Andrea Maria

2013-05-01

The eutherian placenta is considered to possess great plasticity, but it is not clear how this variation reflects adaptation to different ecological niches. Because South America was isolated for most of the Tertiary, it represents a natural laboratory to examine this question. We here describe placentation in three South American groups: Xenarthra have been part of the fauna from at least the mid-Paleocene whereas caviomorph rodents and Neotropical primates are each derived from a single founder that reached South America in the Eocene and Oligocene, respectively. The common ancestor of Xenarthra had a villous, haemochorial placenta, from which the labyrinthine, endotheliochorial placenta of sloths later evolved. Placentation in Caviomorpha follows an extraordinary stable pattern, characterized by a haemomonochorial, labyrinthine and highly lobed structure with specialized growing areas. This pattern was present before arrival of these rodents in South America and enabled a successful radiation especially during the spread of grasslands. Neotropical primates have haemochorial, trabecular placentas with a specialized maternal blood supply; a pattern that contrasts with that of Old World monkeys and may have been present in the founder generation on arrival in South America. In conclusion, there is a dichotomy within Xenarthra but otherwise the ancient South American mammals do not show much variation in principal placental characters. Thus, the successful radiation of these three groups, and their adaptation to diverse ecological niches, did not require substantial alterations in placentation. Copyright © 2013 Wiley Periodicals, Inc.

Differential gene expression profiling of human adipose stem cells differentiating into smooth muscle-like cells by TGFβ1/BMP4

DOE Office of Scientific and Technical Information (OSTI.GOV)

Elçin, Ayşe Eser; Parmaksiz, Mahmut; Dogan, Arin

Regenerative repair of the vascular system is challenging from the perspectives of translational medicine and tissue engineering. There are fundamental hurdles in front of creating bioartificial arteries, which involve recaputilation of the three-layered structure under laboratory settings. Obtaining and maintaining smooth muscle characteristics is an important limitation, as the transdifferentiated cells fail to display mature phenotype. This study aims to shed light on the smooth muscle differentiation of human adipose stem cells (hASCs). To this end, we first acquired hASCs from lipoaspirate samples. Upon characterization, the cells were induced to differentiate into smooth muscle (SM)-like cells using a variety ofmore » inducer combinations. Among all, TGFβ1/BMP4 combination had the highest differentiation efficiency, based on immunohistochemical analyses. hSM-like cell samples were compared to hASCs and to the positive control, human coronary artery-smooth muscle cells (hCA-SMCs) through gene transcription profiling. Microarray findings revealed the activation of gene groups that function in smooth muscle differentiation, signaling pathways, extracellular modeling and cell proliferation. Our results underline the effectiveness of the growth factors and suggest some potential variables for detecting the SM-like cell characteristics. Evidence in transcriptome level was used to evaluate the TGFβ1/BMP4 combination as a previously unexplored effector for the smooth muscle differentiation of adipose stem cells. - Highlights: • Human adipose stem cells (hASCs) were isolated, characterized and cultured. • Growth factor combinations were evaluated for their effectiveness in differentiation using IHC. • hASCs were differentiated into smooth muscle (SM)-like cells using TGF-β1 and BMP4 combination. • Microarray analysis was performed for hASCs, SM-like cells and coronary artery-SMCs. • Microarray data was used to perform hierarchical clustering and

Ultrasound speckle reduction based on fractional order differentiation.

PubMed

Shao, Dangguo; Zhou, Ting; Liu, Fan; Yi, Sanli; Xiang, Yan; Ma, Lei; Xiong, Xin; He, Jianfeng

2017-07-01

Ultrasound images show a granular pattern of noise known as speckle that diminishes their quality and results in difficulties in diagnosis. To preserve edges and features, this paper proposes a fractional differentiation-based image operator to reduce speckle in ultrasound. An image de-noising model based on fractional partial differential equations with balance relation between k (gradient modulus threshold that controls the conduction) and v (the order of fractional differentiation) was constructed by the effective combination of fractional calculus theory and a partial differential equation, and the numerical algorithm of it was achieved using a fractional differential mask operator. The proposed algorithm has better speckle reduction and structure preservation than the three existing methods [P-M model, the speckle reducing anisotropic diffusion (SRAD) technique, and the detail preserving anisotropic diffusion (DPAD) technique]. And it is significantly faster than bilateral filtering (BF) in producing virtually the same experimental results. Ultrasound phantom testing and in vivo imaging show that the proposed method can improve the quality of an ultrasound image in terms of tissue SNR, CNR, and FOM values.

Revisiting the differentiation paradigm in acute promyelocytic leukemia.

PubMed

Ablain, Julien; de The, Hugues

2011-06-02

As the result of intense clinical and basic research, acute promyelocytic leukemia (APL) has progressively evolved from a deadly to a curable disease. Historically, efforts aimed at understanding the molecular bases for therapy response have repeatedly illuminated APL pathogenesis. The classic model attributes this therapeutic success to the transcriptional reactivation elicited by retinoic acid and the resulting overcoming of the differentiation block characteristic of APL blasts. However, in clinical practice, retinoic acid by itself only rarely yields prolonged remissions, even though it induces massive differentiation. In contrast, as a single agent, arsenic trioxide neither directly activates transcription nor triggers terminal differentiation ex vivo, but cures many patients. Here we review the evidence from recent ex vivo and in vivo studies that allow a reassessment of the role of differentiation in APL cure. We discuss alternative models in which PML-RARA degradation and the subsequent loss of APL cell self-renewal play central roles. Rather than therapy aimed at inducing differentiation, targeting cancer cell self-renewal may represent a more effective goal, achievable by a broader range of therapeutic agents.

Self-Consistent Sources Extensions of Modified Differential-Difference KP Equation

NASA Astrophysics Data System (ADS)

Gegenhasi; Li, Ya-Qian; Zhang, Duo-Duo

2018-04-01

In this paper, we investigate a modified differential-difference KP equation which is shown to have a continuum limit into the mKP equation. It is also shown that the solution of the modified differential-difference KP equation is related to the solution of the differential-difference KP equation through a Miura transformation. We first present the Grammian solution to the modified differential-difference KP equation, and then produce a coupled modified differential-difference KP system by applying the source generation procedure. The explicit N-soliton solution of the resulting coupled modified differential-difference system is expressed in compact forms by using the Grammian determinant and Casorati determinant. We also construct and solve another form of the self-consistent sources extension of the modified differential-difference KP equation, which constitutes a Bäcklund transformation for the differential-difference KP equation with self-consistent sources. Supported by the National Natural Science Foundation of China under Grant Nos. 11601247 and 11605096, the Natural Science Foundation of Inner Mongolia Autonomous Region under Grant Nos. 2016MS0115 and 2015MS0116 and the Innovation Fund Programme of Inner Mongolia University No. 20161115

Achaete-Scute Homolog 1 Expression Controls Cellular Differentiation of Neuroblastoma

PubMed Central

Kasim, Mumtaz; Heß, Vicky; Scholz, Holger; Persson, Pontus B.; Fähling, Michael

2016-01-01

Neuroblastoma, the major cause of infant cancer deaths, results from fast proliferation of undifferentiated neuroblasts. Treatment of high-risk neuroblastoma includes differentiation with retinoic acid (RA); however, the resistance of many of these tumors to RA-induced differentiation poses a considerable challenge. Human achaete-scute homolog 1 (hASH1) is a proneural basic helix-loop-helix transcription factor essential for neurogenesis and is often upregulated in neuroblastoma. Here, we identified a novel function for hASH1 in regulating the differentiation phenotype of neuroblastoma cells. Global analysis of 986 human neuroblastoma datasets revealed a negative correlation between hASH1 and neuron differentiation that was independent of the N-myc (MYCN) oncogene. Using RA to induce neuron differentiation in two neuroblastoma cell lines displaying high and low levels of hASH1 expression, we confirmed the link between hASH1 expression and the differentiation defective phenotype, which was reversed by silencing hASH1 or by hypoxic preconditioning. We further show that hASH1 suppresses neuronal differentiation by inhibiting transcription at the RA receptor element. Collectively, our data indicate hASH1 to be key for understanding neuroblastoma resistance to differentiation therapy and pave the way for hASH1-targeted therapies for augmenting the response of neuroblastoma to differentiation therapy. PMID:28066180

Fibronectin is a survival factor for differentiated osteoblasts

NASA Technical Reports Server (NTRS)

Globus, R. K.; Doty, S. B.; Lull, J. C.; Holmuhamedov, E.; Humphries, M. J.; Damsky, C. H.

1998-01-01

The skeletal extracellular matrix produced by osteoblasts contains the glycoprotein fibronectin, which regulates the adhesion, differentiation and function of various adherent cells. Interactions with fibronectin are required for osteoblast differentiation in vitro, since fibronectin antagonists added to cultures of immature fetal calvarial osteoblasts inhibit their progressive differentiation. To determine if fibronectin plays a unique role in fully differentiated osteoblasts, cultures that had already formed mineralized nodules in vitro were treated with fibronectin antagonists. Fibronectin antibodies caused >95% of the cells in the mature cultures to display characteristic features of apoptosis (nuclear condensation, apoptotic body formation, DNA laddering) within 24 hours. Cells appeared to acquire sensitivity to fibronectin antibody-induced apoptosis as a consequence of differentiation, since antibodies failed to kill immature cells and the first cells killed were those associated with mature nodules. Intact plasma fibronectin, as well as fragments corresponding to the amino-terminal, cell-binding, and carboxy-terminal domains of fibronectin, independently induced apoptosis of mature (day-13), but not immature (day-4), osteoblasts. Finally, transforming growth factor-beta1 partially protected cells from the apoptotic effects of fibronectin antagonists. Thus, in the course of maturation cultured osteoblasts switch from depending on fibronectin for differentiation to depending on fibronectin for survival. These data suggest that fibronectin, together with transforming growth factor-beta1, may affect bone formation, in part by regulating the survival of osteoblasts.

Actin depolymerization enhances adipogenic differentiation in human stromal stem cells.

PubMed

Chen, Li; Hu, Huimin; Qiu, Weimin; Shi, Kaikai; Kassem, Moustapha

2018-05-01

Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined the effect of direct modulation of actin microfilament dynamics on adipocyte differentiation. Stabilizing actin filaments in hMSCs by siRNA-mediated knock down of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) or treating the cells by Phalloidin reduced adipocyte differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating hMSCs by Cytochalasin D inhibited ERK and Smad2 signaling and this was associated with enhanced adipocyte differentiation. On the other hand, Phalloidin enhanced ERK and Smad2 signaling, but inhibited adipocyte differentiation which was rescued by ERK specific chemical inhibitor U0126. Our data provide a link between restructuring of hMSCs cytoskeleton and hMSCs lineage commitment and differentiation. Copyright © 2018 Elsevier B.V. All rights reserved.

Differential Si ring resonators for label-free biosensing

NASA Astrophysics Data System (ADS)

Taniguchi, Tomoya; Yokoyama, Shuhei; Amemiya, Yoshiteru; Ikeda, Takeshi; Kuroda, Akio; Yokoyama, Shin

2016-04-01

Differential Si ring optical resonator sensors have been fabricated. Their detection sensitivity was 10-3-10-2% for sucrose solution, which corresponds to a sensitivity of ˜1.0 ng/ml for prostate-specific antigen (PSA), which is satisfactory for practical use. In the differential sensing the input light is incident to two rings, and one of the outputs is connected to a π phase shifter then the two outputs are merged again. For the differential detection, not only is the common-mode noise canceled, resulting in high sensitivity, but also the temperature stability is much improved. A fluid channel is fabricated so that the detecting liquid flows to the detection ring and the reference liquid flows to the reference ring. We have proposed a method of obtaining a constant sensitivity for the integrated sensors even though the resonance wavelengths of the two rings of the differential sensor are slightly different. It was found that a region exists with a linear relationship between the differential output and the difference in the resonance wavelengths of the two rings. By intentionally differentiating the resonance wavelengths in this linear region, the sensors have a constant sensitivity. Many differential sensors with different ring spaces have been fabricated and the output scattering characteristics were statistically evaluated. As a result, a standard deviation of resonance wavelength σ = 8 × 10-3 nm was obtained for a ring space of 31 µm. From the width of the linear region and the standard deviation, it was estimated from the Gaussian distribution of the resonance wavelength that 93.8% of the devices have the same sensitivity.

Pharmacologic inhibition of lactate production prevents myofibroblast differentiation.

PubMed

Kottmann, Robert Matthew; Trawick, Emma; Judge, Jennifer L; Wahl, Lindsay A; Epa, Amali P; Owens, Kristina M; Thatcher, Thomas H; Phipps, Richard P; Sime, Patricia J

2015-12-01

Myofibroblasts are one of the primary cell types responsible for the accumulation of extracellular matrix in fibrosing diseases, and targeting myofibroblast differentiation is an important therapeutic strategy for the treatment of pulmonary fibrosis. Transforming growth factor-β (TGF-β) has been shown to be an important inducer of myofibroblast differentiation. We previously demonstrated that lactate dehydrogenase and its metabolic product lactic acid are important mediators of myofibroblast differentiation, via acid-induced activation of latent TGF-β. Here we explore whether pharmacologic inhibition of LDH activity can prevent TGF-β-induced myofibroblast differentiation. Primary human lung fibroblasts from healthy patients and those with pulmonary fibrosis were treated with TGF-β and or gossypol, an LDH inhibitor. Protein and RNA were analyzed for markers of myofibroblast differentiation and extracellular matrix generation. Gossypol inhibited TGF-β-induced expression of the myofibroblast marker α-smooth muscle actin (α-SMA) in a dose-dependent manner in both healthy and fibrotic human lung fibroblasts. Gossypol also inhibited expression of collagen 1, collagen 3, and fibronectin. Gossypol inhibited LDH activity, the generation of extracellular lactic acid, and the rate of extracellular acidification in a dose-dependent manner. Furthermore, gossypol inhibited TGF-β bioactivity in a dose-dependent manner. Concurrent treatment with an LDH siRNA increased the ability of gossypol to inhibit TGF-β-induced myofibroblast differentiation. Gossypol inhibits TGF-β-induced myofibroblast differentiation through inhibition of LDH, inhibition of extracellular accumulation of lactic acid, and inhibition of TGF-β bioactivity. These data support the hypothesis that pharmacologic inhibition of LDH may play an important role in the treatment of pulmonary fibrosis. Copyright © 2015 the American Physiological Society.

A New Module in Neural Differentiation Control: Two MicroRNAs Upregulated by Retinoic Acid, miR-9 and -103, Target the Differentiation Inhibitor ID2

PubMed Central

Savino, Mauro; Laneve, Pietro; Caffarelli, Elisa; Nasi, Sergio

2012-01-01

The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs) are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells – miR-9 and miR-103 – restrain ID2 expression by directly targeting the coding sequence and 3′ untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development. PMID:22848373

N-person differential games. Part 2: The penalty method

NASA Technical Reports Server (NTRS)

Chen, G.; Mills, W. H.; Zheng, Q.; Shaw, W. H.

1983-01-01

The equilibrium strategy for N-person differential games can be found by studying a min-max problem subject to differential systems constraints. The differential constraints are penalized and finite elements are used to compute numerical solutions. Convergence proof and error estimates are given. Numerical results are also included and compared with those obtained by the dual method.

Differential invariants in nonclassical models of hydrodynamics

NASA Astrophysics Data System (ADS)

Bublik, Vasily V.

2017-10-01

In this paper, differential invariants are used to construct solutions for equations of the dynamics of a viscous heat-conducting gas and the dynamics of a viscous incompressible fluid modified by nanopowder inoculators. To describe the dynamics of a viscous heat-conducting gas, we use the complete system of Navier—Stokes equations with allowance for heat fluxes. Mathematical description of the dynamics of liquid metals under high-energy external influences (laser radiation or plasma flow) includes, in addition to the Navier—Stokes system of an incompressible viscous fluid, also heat fluxes and processes of nonequilibrium crystallization of a deformable fluid. Differentially invariant solutions are a generalization of partially invariant solutions, and their active study for various models of continuous medium mechanics is just beginning. Differentially invariant solutions can also be considered as solutions with differential constraints; therefore, when developing them, the approaches and methods developed by the science schools of academicians N. N. Yanenko and A. F. Sidorov will be actively used. In the construction of partially invariant and differentially invariant solutions, there are overdetermined systems of differential equations that require a compatibility analysis. The algorithms for reducing such systems to involution in a finite number of steps are described by Cartan, Finikov, Kuranishi, and other authors. However, the difficultly foreseeable volume of intermediate calculations complicates their practical application. Therefore, the methods of computer algebra are actively used here, which largely helps in solving this difficult problem. It is proposed to use the constructed exact solutions as tests for formulas, algorithms and their software implementations when developing and creating numerical methods and computational program complexes. This combination of effective numerical methods, capable of solving a wide class of problems, with

Eclipse and noneclipse differential photoelectron flux.

NASA Technical Reports Server (NTRS)

Knudsen, W. C.; Sharp, G. W.

1972-01-01

Differential photoelectron flux in the energy range of 3 to 50 eV has been measured in the lower ionosphere both during the March 7, 1970, solar eclipse and during a period 24 hours earlier. The two measurements were made with identical retarding potential analyzers carried on Nike-Apache rocket flights to a peak altitude of approximately 180 km. The differential electron flux spectrum within totality on the eclipse flight had the same shape but was a factor of 10 smaller in magnitude than that measured on the control day at altitudes between 120 and 180 km, an expected result for an eclipse function decreasing to 1/10 at totality. The differential flux spectrum measured in full sun has the same general energy dependence as that reported by Doering et al. (1970) but is larger by a factor of 2 to 10, depending on altitude.

Samples from Differentiated Asteroids; Regolithic Achondrites

NASA Technical Reports Server (NTRS)

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

2011-01-01

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

Support Vector Machines for Differential Prediction

PubMed Central

Kuusisto, Finn; Santos Costa, Vitor; Nassif, Houssam; Burnside, Elizabeth; Page, David; Shavlik, Jude

2015-01-01

Machine learning is continually being applied to a growing set of fields, including the social sciences, business, and medicine. Some fields present problems that are not easily addressed using standard machine learning approaches and, in particular, there is growing interest in differential prediction. In this type of task we are interested in producing a classifier that specifically characterizes a subgroup of interest by maximizing the difference in predictive performance for some outcome between subgroups in a population. We discuss adapting maximum margin classifiers for differential prediction. We first introduce multiple approaches that do not affect the key properties of maximum margin classifiers, but which also do not directly attempt to optimize a standard measure of differential prediction. We next propose a model that directly optimizes a standard measure in this field, the uplift measure. We evaluate our models on real data from two medical applications and show excellent results. PMID:26158123

Support Vector Machines for Differential Prediction.

PubMed

Kuusisto, Finn; Santos Costa, Vitor; Nassif, Houssam; Burnside, Elizabeth; Page, David; Shavlik, Jude

Machine learning is continually being applied to a growing set of fields, including the social sciences, business, and medicine. Some fields present problems that are not easily addressed using standard machine learning approaches and, in particular, there is growing interest in differential prediction . In this type of task we are interested in producing a classifier that specifically characterizes a subgroup of interest by maximizing the difference in predictive performance for some outcome between subgroups in a population. We discuss adapting maximum margin classifiers for differential prediction. We first introduce multiple approaches that do not affect the key properties of maximum margin classifiers, but which also do not directly attempt to optimize a standard measure of differential prediction. We next propose a model that directly optimizes a standard measure in this field, the uplift measure. We evaluate our models on real data from two medical applications and show excellent results.

Detection of explosives by differential hyperspectral imaging

NASA Astrophysics Data System (ADS)

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

2014-02-01

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

Differentiability of correlations in realistic quantum mechanics

DOE Office of Scientific and Technical Information (OSTI.GOV)

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

2015-09-15

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

Modeling to Optimize Terminal Stem Cell Differentiation

PubMed Central

Gallicano, G. Ian

2013-01-01

Embryonic stem cell (ESC), iPCs, and adult stem cells (ASCs) all are among the most promising potential treatments for heart failure, spinal cord injury, neurodegenerative diseases, and diabetes. However, considerable uncertainty in the production of ESC-derived terminally differentiated cell types has limited the efficiency of their development. To address this uncertainty, we and other investigators have begun to employ a comprehensive statistical model of ESC differentiation for determining the role of intracellular pathways (e.g., STAT3) in ESC differentiation and determination of germ layer fate. The approach discussed here applies the Baysian statistical model to cell/developmental biology combining traditional flow cytometry methodology and specific morphological observations with advanced statistical and probabilistic modeling and experimental design. The final result of this study is a unique tool and model that enhances the understanding of how and when specific cell fates are determined during differentiation. This model provides a guideline for increasing the production efficiency of therapeutically viable ESCs/iPSCs/ASC derived neurons or any other cell type and will eventually lead to advances in stem cell therapy. PMID:24278782

Apparatus for sampling and characterizing aerosols

DOEpatents

Dunn, Patrick F.; Herceg, Joseph E.; Klocksieben, Robert H.

1986-01-01

Apparatus for sampling and characterizing aerosols having a wide particle size range at relatively low velocities may comprise a chamber having an inlet and an outlet, the chamber including: a plurality of vertically stacked, successive particle collection stages; each collection stage includes a separator plate and a channel guide mounted transverse to the separator plate, defining a labyrinthine flow path across the collection stage. An opening in each separator plate provides a path for the aerosols from one collection stage to the next. Mounted within each collection stage are one or more particle collection frames.

Differentially Private Frequent Subgraph Mining

PubMed Central

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

2016-01-01

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

Solving constant-coefficient differential equations with dielectric metamaterials

NASA Astrophysics Data System (ADS)

Zhang, Weixuan; Qu, Che; Zhang, Xiangdong

2016-07-01

Recently, the concept of metamaterial analog computing has been proposed (Silva et al 2014 Science 343 160-3). Some mathematical operations such as spatial differentiation, integration, and convolution, have been performed by using designed metamaterial blocks. Motivated by this work, we propose a practical approach based on dielectric metamaterial to solve differential equations. The ordinary differential equation can be solved accurately by the correctly designed metamaterial system. The numerical simulations using well-established numerical routines have been performed to successfully verify all theoretical analyses.

The neuronal differentiation process involves a series of antioxidant proteins.

PubMed

Oh, J-E; Karlmark Raja, K; Shin, J-H; Hengstschläger, M; Pollak, A; Lubec, G

2005-11-01

Involvement of individual antioxidant proteins (AOXP) and antioxidants in the differentiation process has been already reported. A systematic search strategy for detecting differentially regulated AOXP in neuronal differentiation, however, has not been published so far. The aim of this study was to provide an analytical tool identifying AOXP and to generate a differentiation-related AOXP expressional pattern. The undifferentiated N1E-115 neuroblastoma cell line was switched into a neuronal phenotype by DMSO treatment and used for proteomic experiments: We used two-dimensional gel electrophoresis followed by unambiguous mass spectrometrical (MALDI-TOF-TOF) identification of proteins to generate a map of AOXP. 16 AOXP were unambiguously determined in both cell lines; catalase, thioredoxin domain-containing protein 4 and hypothetical glutaredoxin/glutathione S-transferase C terminus-containing protein were detectable in the undifferentiated cells only. Five AOXP were observed in both, undifferentiated and differentiated cells and thioredoxin, thioredoxin-like protein p19, thioredoxin reductase 1, superoxide dismutases (Mn and Cu-Zn), glutathione synthetase, glutathione S-transferase P1 and Mu1 were detected in differentiated cells exclusively. Herein a differential expressional pattern is presented that reveals so far unpublished antioxidant principles involved in neuronal differentiation by a protein chemical approach, unambiguously identifying AOXP. This finding not only shows concomitant determination of AOXP but also serves as an analytical tool and forms the basis for design of future studies addressing AOXP and differentiation per se.

Key Transcription Factors in the Differentiation of Mesenchymal Stem Cells

PubMed Central

Almalki, Sami G.; Agrawal, Devendra K.

2016-01-01

Mesenchymal stem cells (MSCs) are multipotent cells that represent a promising source for regenerative medicine. MSCs are capable of osteogenic, chondrogenic, adipogenic and myogenic differentiation. Efficacy of differentiated MSCs to regenerate cells in the injured tissues requires the ability to maintain the differentiation toward the desired cell fate. Since MSCs represent an attractive source for autologous transplantation, cellular and molecular signaling pathways and micro-environmental changes have been studied in order to understand the role of cytokines, chemokines, and transcription factors on the differentiation of MSCs. The differentiation of MSC into a mesenchymal lineage is genetically manipulated and promoted by specific transcription factors associated with a particular cell lineage. Recent studies have explored the integration of transcription factors, including Runx2, Sox9, PPARγ, MyoD, GATA4, and GATA6 in the differentiation of MSCs. Therefore, the overexpression of a single transcription factor in MSCs may promote trans-differentiation into specific cell lineage, which can be used for treatment of some diseases. In this review, we critically discussed and evaluated the role of transcription factors and related signaling pathways that affect the differentiation of MSCs toward adipocytes, chondrocytes, osteocytes, skeletal muscle cells, cardiomyocytes, and smooth muscle cells. PMID:27012163

Clonal analysis of human embryonic stem cell differentiation into teratomas.

PubMed

Blum, Barak; Benvenisty, Nissim

2007-08-01

Differentiation of human embryonic stem cells (HESCs) can be studied in vivo through the induction of teratomas in immune-deficient mice. Cells within the teratomas differentiate into all three embryonic germ layers. However, the exact nature of the proliferation and differentiation of HESCs within the teratoma is not fully characterized, and it is not clear whether the differentiation is cell autonomous or affected by neighboring cells. Here, we establish a genetic approach to study the clonality of differentiation in teratomas using a mixture of HESC lines. We first demonstrate, by means of 5-bromo-2'-deoxyuridine incorporation, that cell proliferation occurs throughout the teratoma, and that there are no clusters of undifferentiated-proliferating cells. Using a combination of laser capture microdissection and DNA fingerprinting analysis, we show that different cell lines contribute mutually to the same distinctive tissue structures. Further support for the nonclonal differentiation within the teratoma was achieved by fluorescence in situ hybridization analysis of sex chromosomes. We therefore suggest that in vivo differentiation of HESCs is polyclonal and, thus, may not be cell autonomous, stressing the need for a three-dimensional growth in order to achieve complex differentiation of HESCs. Disclosure of potential conflicts of interest is found at the end of this article.

Decoding Crucial LncRNAs Implicated in Neurogenesis and Neurological Disorders.

PubMed

Ayana, R; Singh, Shailja; Pati, Soumya

2017-04-15

Unraveling transcriptional heterogeneity and the labyrinthine nature of neurodevelopment can probe insights into neuropsychiatric disorders. It is noteworthy that adult neurogenesis is restricted to the subventricular and subgranular zones of the brain. Recent studies suggest long non-coding RNAs (lncRNAs) as an avant-garde class of regulators implicated in neurodevelopment. But, paucity exists in the knowledge regarding lncRNAs in neurogenesis and their associations with neurodevelopmental defects. To address this, we extensively reviewed the existing literature databases as well as performed relevant in-silico analysis. We utilized Allen Brain Atlas (ABA) differential search module and generated a catalogue of ∼30,000 transcripts specific to the neurogenic zones, including coding and non-coding transcripts. To explore the existing lncRNAs reported in neurogenesis, we performed extensive literature mining and identified 392 lncRNAs. These degenerate lncRNAs were mapped onto the ABA transcript list leading to detection of 20 lncRNAs specific to neurogenic zones (Dentate gyrus/Lateral ventricle), among which 10 showed associations to several neurodevelopmental disorders following in-silico mapping onto brain disease databases like Simons Foundation Autism Research Initiative, AutDB, and lncRNADisease. Notably, using ABA correlation module, we could establish lncRNA-to-mRNA coexpression networks for the above 10 candidate lncRNAs. Finally, pathway prediction revealed physical, biochemical, or regulatory interactions for nine lncRNAs. In addition, ABA differential search also revealed 54 novel significant lncRNAs from the null set (∼30,000). Conclusively, this review represents an updated catalogue of lncRNAs in neurogenesis and neurological diseases, and overviews the field of OMICs-based data analysis for understanding lncRNome-based regulation in neurodevelopment.

Differentiating youth who are bullied from other victims of peer-aggression: the importance of differential power and repetition

PubMed Central

Ybarra, Michele L.; Espelage, Dorothy L.; Mitchell, Kimberly J.

2014-01-01

Purpose Examine whether: 1) among youth who report being bullied, differential power and repetition are useful in identifying youth who are more or less affected by the victimization experience; and 2) bullying and more generalized peer aggression are distinct or overlapping constructs. Methods Data for the Teen Health and Technology (THT) study were collected online between August 2010 and January 2011 from 3,989 13–18 year olds. Data from the Growing up with Media (GuwM) study (Wave 3) were collected online in 2008 from 1,157 12–17 year olds. Results In the THT study, youth who reported neither differential power nor repetition had the lowest rates of interference with daily functioning. Youth who reported either differential power or repetition had higher rates; but the highest rates of interference with daily functioning were observed among youth who reported both differential power and repetition. In the GuwM study, youth were victims of online generalized peer aggression (30%) or both online generalized peer aggression and cyberbullying (16%), but rarely cyberbullying alone (1%). Conclusions Both differential power and repetition are key in identifying youth who are bullied and at particular risk for concurrent psychosocial challenge. Each feature needs to be measured directly. Generalized peer aggression appears to be a broader form of violence compared to bullying. It needs to be recognized that youth who are victimized but do not meet the criteria of bullying have elevated rates of problems. They are an important, albeit non-bullied, group of victimized youth to be included in research. PMID:24726463

Differential Experience of Siblings in the Same Family.

ERIC Educational Resources Information Center

Daniels, Denise; Plomin, Robert

1985-01-01

Used the Sibling Inventory of Differential Experience with 396 adolescent and young adult children to determine the extent to which genetic differences between siblings or sibling differences in family constellation variables were responsible for differential experiences. (HOD)

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…

Genetic differentiation among populations of marine algae

NASA Astrophysics Data System (ADS)

Innes, D. J.

1984-09-01

Most of the information for genetic differentiation among populations of marine algae is from studies on ecotypic variation. Physiological ecotypes have been described for individuals showing different responses to temperature and salinity conditions. Morphological ecotypes have also been found associated with areas differing in wave exposure or different intertidal positions. Little is known on how genetic variation is organized within and between populations of marine algae. The occurrence of ecotypic variation in some species is evidence for genetic differentiation among populations resulting from selection by the local environment. The rate of dispersal and subsequent gene flow will also affect the level of differentiation among populations. In species with low dispersal, differentiation can arise through chance founder events or random genetic drift. The few studies available have shown that species of algae exhibit a range of dispersal capabilities. This information can be useful for predicting the potential level of genetic differentiation among populations of these species. Crossing experiments with several species of algae have shown that populations separated by a considerable distance can be interfertile. In some cases individuals from these populations have been found to be morphologically distinct. Crosses have been used to study the genetic basis of this variation and are evidence for genetic differentiation among the populations sampled. Genetic variation of enzyme proteins detected by electrophoresis provides an additional method for measuring genetic variation within and between populations of marine algae. Electrophoretic methods have previously been used to study systematic problems in algae. However, there have been few attempts to use electrophoretic variation to study the genetic structure of populations of marine algae. This approach is outlined and includes some of the potential problems associated with interpreting electrophoretic data

Differential pleiotropy and HOX functional organization.

PubMed

Sivanantharajah, Lovesha; Percival-Smith, Anthony

2015-02-01

Key studies led to the idea that transcription factors are composed of defined modular protein motifs or domains, each with separable, unique function. During evolution, the recombination of these modular domains could give rise to transcription factors with new properties, as has been shown using recombinant molecules. This archetypic, modular view of transcription factor organization is based on the analyses of a few transcription factors such as GAL4, which may represent extreme exemplars rather than an archetype or the norm. Recent work with a set of Homeotic selector (HOX) proteins has revealed differential pleiotropy: the observation that highly-conserved HOX protein motifs and domains make small, additive, tissue specific contributions to HOX activity. Many of these differentially pleiotropic HOX motifs may represent plastic sequence elements called short linear motifs (SLiMs). The coupling of differential pleiotropy with SLiMs, suggests that protein sequence changes in HOX transcription factors may have had a greater impact on morphological diversity during evolution than previously believed. Furthermore, differential pleiotropy may be the genetic consequence of an ensemble nature of HOX transcription factor allostery, where HOX proteins exist as an ensemble of states with the capacity to integrate an extensive array of developmental information. Given a new structural model for HOX functional domain organization, the properties of the archetypic TF may require reassessment. Copyright © 2014 Elsevier Inc. All rights reserved.

Ordinary differential equations with applications in molecular biology.

PubMed

Ilea, M; Turnea, M; Rotariu, M

2012-01-01

Differential equations are of basic importance in molecular biology mathematics because many biological laws and relations appear mathematically in the form of a differential equation. In this article we presented some applications of mathematical models represented by ordinary differential equations in molecular biology. The vast majority of quantitative models in cell and molecular biology are formulated in terms of ordinary differential equations for the time evolution of concentrations of molecular species. Assuming that the diffusion in the cell is high enough to make the spatial distribution of molecules homogenous, these equations describe systems with many participating molecules of each kind. We propose an original mathematical model with small parameter for biological phospholipid pathway. All the equations system includes small parameter epsilon. The smallness of epsilon is relative to the size of the solution domain. If we reduce the size of the solution region the same small epsilon will result in a different condition number. It is clear that the solution for a smaller region is less difficult. We introduce the mathematical technique known as boundary function method for singular perturbation system. In this system, the small parameter is an asymptotic variable, different from the independent variable. In general, the solutions of such equations exhibit multiscale phenomena. Singularly perturbed problems form a special class of problems containing a small parameter which may tend to zero. Many molecular biology processes can be quantitatively characterized by ordinary differential equations. Mathematical cell biology is a very active and fast growing interdisciplinary area in which mathematical concepts, techniques, and models are applied to a variety of problems in developmental medicine and bioengineering. Among the different modeling approaches, ordinary differential equations (ODE) are particularly important and have led to significant advances

Defining a Model for Mitochondrial Function in mESC Differentiation

EPA Science Inventory

Defining a Model for Mitochondrial Function in mESC DifferentiationDefining a Model for Mitochondrial Function in mESC Differentiation Differentiating embryonic stem cells (ESCs) undergo mitochondrial maturation leading to a switch from a system dependent upon glycolysis to a re...

Fibromodulin modulates myoblast differentiation by controlling calcium channel.

PubMed

Lee, Eun Ju; Nam, Joo Hyun; Choi, Inho

2018-06-16

Fibromodulin (FMOD) is a proteoglycan present in extracellular matrix (ECM). Based on our previous findings that FMOD controls myoblast differentiation by regulating the gene expressions of collagen type I alpha 1 (COL1α1) and integral membrane protein 2 A (Itm2a), we undertook this study to investigate relationships between FMOD and calcium channels and to understand further the mechanism by which they control myoblast differentiation. Gene expression studies and luciferase reporter assays showed FMOD affected calcium channel gene expressions by regulating calcium channel gene promoter, and patch-clamp experiments showed both L- and T-type calcium channel currents were almost undetectable in FMOD knocked down cells. In addition, gene knock-down studies demonstrated the COL1α1 and Itm2a genes both regulate the expressions of calcium channel genes. Studies using a cardiotoxin-induced mouse muscle injury model demonstrated calcium channels play important roles in the regeneration of muscle tissue, possibly by promoting the differentiation of muscle stem cells (MSCs). Summarizing, the study demonstrates ECM components secreted by myoblasts during differentiation provide an essential environment for muscle differentiation and regeneration. Copyright © 2018 Elsevier Inc. All rights reserved.

For numerical differentiation, dimensionality can be a blessing!

NASA Astrophysics Data System (ADS)

Anderssen, Robert S.; Hegland, Markus

Finite difference methods, such as the mid-point rule, have been applied successfully to the numerical solution of ordinary and partial differential equations. If such formulas are applied to observational data, in order to determine derivatives, the results can be disastrous. The reason for this is that measurement errors, and even rounding errors in computer approximations, are strongly amplified in the differentiation process, especially if small step-sizes are chosen and higher derivatives are required. A number of authors have examined the use of various forms of averaging which allows the stable computation of low order derivatives from observational data. The size of the averaging set acts like a regularization parameter and has to be chosen as a function of the grid size h. In this paper, it is initially shown how first (and higher) order single-variate numerical differentiation of higher dimensional observational data can be stabilized with a reduced loss of accuracy than occurs for the corresponding differentiation of one-dimensional data. The result is then extended to the multivariate differentiation of higher dimensional data. The nature of the trade-off between convergence and stability is explicitly characterized, and the complexity of various implementations is examined.

Delivery of Differentiation Factors by Mesoporous Silica Particles Assists Advanced Differentiation of Transplanted Murine Embryonic Stem Cells

PubMed Central

Kozhevnikova, Mariya; König, Niclas; Zhou, Chunfang; Leao, Richardson; Knöpfel, Thomas; Pankratova, Stanislava; Trolle, Carl; Berezin, Vladimir; Bock, Elisabeth; Aldskogius, Håkan

2013-01-01

Stem cell transplantation holds great hope for the replacement of damaged cells in the nervous system. However, poor long-term survival after transplantation and insufficiently robust differentiation of stem cells into specialized cell types in vivo remain major obstacles for clinical application. Here, we report the development of a novel technological approach for the local delivery of exogenous trophic factor mimetics to transplanted cells using specifically designed silica nanoporous particles. We demonstrated that delivering Cintrofin and Gliafin, established peptide mimetics of the ciliary neurotrophic factor and glial cell line-derived neurotrophic factor, respectively, with these particles enabled not only robust functional differentiation of motor neurons from transplanted embryonic stem cells but also their long-term survival in vivo. We propose that the delivery of growth factors by mesoporous nanoparticles is a potentially versatile and widely applicable strategy for efficient differentiation and functional integration of stem cell derivatives upon transplantation. PMID:24089415

Advances in the Diagnosis and Management of Well-Differentiated and Intermediate-Differentiated Neuroendocrine Tumors of the Lung.

PubMed

Wolin, Edward M

2017-05-01

Neuroendocrine tumors (NETs) are a rare, heterogeneous group of malignancies that arise from neuroendocrine cells throughout the body, with the lungs and GI tract being the most common sites of origin. Despite increasing incidence, awareness of lung NETs remains low among thoracic specialists who are often involved in the assessment and early treatment of these patients. Successful treatment requires accurate and timely diagnosis; however, classification can be challenging, particularly for well-differentiated and intermediate-differentiated lung NET types (typical carcinoids [TC] and atypical carcinoids [AC]). Diagnosis and management of lung NETs are further complicated by the nonspecificity of symptoms, variable natural history, and lack of high-level clinical evidence; a multidisciplinary approach is required, which has been shown to improve prognosis. Currently, surgery remains the only curative option for TC/AC. Inconsistencies between guideline recommendations for systemic therapies, especially for chemotherapy, result in a lack of consensus on a standardized treatment for unresectable disease. Recent data from the Phase III RAD001 in Advanced Neuroendocrine Tumors, Fourth Trial (RADIANT-4), which contained a large population of patients with advanced, well-differentiated, nonfunctional lung NETs in addition to those with GI NETs, found a reduced risk of disease progression and death with everolimus compared with placebo, leading to US approval of everolimus in these patient populations. This study is the first high-level therapeutic evidence in patients with TC/AC, and everolimus is currently the only agent approved for treatment of TC/AC. Increased awareness, prompt diagnosis, and additional adequately powered controlled clinical trials of patients with well-differentiated and intermediate-differentiated lung NETs are needed to further improve evidence-based care. Copyright © 2016 The Author. Published by Elsevier Inc. All rights reserved.

Bropirimine inhibits osteoclast differentiation through production of interferon-β

DOE Office of Scientific and Technical Information (OSTI.GOV)

Suzuki, Hiroaki; Mochizuki, Ayako; Yoshimura, Kentaro

Bropirimine is a synthetic agonist for toll-like receptor 7 (TLR7). In this study, we investigated the effects of bropirimine on differentiation and bone-resorbing activity of osteoclasts in vitro. Bropirimine inhibited osteoclast differentiation of mouse bone marrow-derived macrophages (BMMs) induced by receptor activator of nuclear factor κB ligand (RANKL) in a concentration-dependent manner. Furthermore, it suppressed the mRNA expression of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1), a master transcription factor for osteoclast differentiation, without affecting BMM viability. Bropirimine also inhibited osteoclast differentiation induced in co-cultures of mouse bone marrow cells (BMCs) and mouse osteoblastic UAMS-32 cells in the presencemore » of activated vitamin D{sub 3}. Bropirimine partially suppressed the expression of RANKL mRNA in UAMS-32 cells induced by activated vitamin D{sub 3}. Finally, the anti-interferon-β (IFN-β) antibody restored RANKL-dependent differentiation of BMMs into osteoclasts suppressed by bropirimine. These results suggest that bropirimine inhibits differentiation of osteoclast precursor cells into osteoclasts via TLR7-mediated production of IFN-β.« less

Using Technology to Facilitate Differentiated High School Science Instruction

NASA Astrophysics Data System (ADS)

Maeng, Jennifer L.

2017-10-01

This qualitative investigation explored the beliefs and practices of one secondary science teacher, Diane, who differentiated instruction and studied how technology facilitated her differentiation. Diane was selected based on the results of a previous study, in which data indicated that Diane understood how to design and implement proactively planned, flexible, engaging instructional activities in response to students' learning needs better than the other study participants. Data for the present study included 3 h of semi-structured interview responses, 37.5 h of observations of science instruction, and other artifacts such as instructional materials. This variety of data allowed for triangulation of the evidence. Data were analyzed using a constant comparative approach. Results indicated that technology played an integral role in Diane's planning and implementation of differentiated science lessons. The technology-enhanced differentiated lessons employed by Diane typically attended to students' different learning profiles or interest through modification of process or product. This study provides practical strategies for science teachers beginning to differentiate instruction, and recommendations for science teacher educators and school and district administrators. Future research should explore student outcomes, supports for effective formative assessment, and technology-enhanced readiness differentiation among secondary science teachers.

Autophagy dictates metabolism and differentiation of inflammatory immune cells

PubMed Central

Riffelmacher, Thomas; Richter, Felix Clemens; Simon, Anna Katharina

2018-01-01

ABSTRACT The role of macroautophagy/autophagy, a conserved lysosomal degradation pathway, during cellular differentiation has been well studied over the last decade. In particular, evidence for its role during immune cell differentiation is growing. Despite the description of a variety of dramatic immune phenotypes in tissue-specific autophagy knockout models, the underlying mechanisms are still under debate. One of the proposed mechanisms is the impact of autophagy on the altered metabolic states during immune cell differentiation. This concept is strengthened through novel molecular insights into how AMPK and MTOR signaling cascades affect both autophagy and metabolism. In this review, we discuss direct and indirect evidence linking autophagy, metabolic pathways and immune cell differentiation including T, B, and innate lymphocytes as well as in myeloid cells that are direct mediators of inflammation. Herein, we propose a model for autophagy-driven immunometabolism controlling immune cell differentiation. PMID:28806133

Power-law confusion: You say incremental, I say differential

NASA Technical Reports Server (NTRS)

Colwell, Joshua E.

1993-01-01

Power-law distributions are commonly used to describe the frequency of occurrences of crater diameters, stellar masses, ring particle sizes, planetesimal sizes, and meteoroid masses to name a few. The distributions are simple, and this simplicity has led to a number of misstatements in the literature about the kind of power-law that is being used: differential, cumulative, or incremental. Although differential and cumulative power-laws are mathematically trivial, it is a hybrid incremental distribution that is often used and the relationship between the incremental distribution and the differential or cumulative distributions is not trivial. In many cases the slope of an incremental power-law will be nearly identical to the slope of the cumulative power-law of the same distribution, not the differential slope. The discussion that follows argues for a consistent usage of these terms and against the oft-made implicit claim that incremental and differential distributions are indistinguishable.

Well-differentiated liposarcoma of the tongue.

PubMed

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

2002-01-01

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

Some problems in fractal differential equations

NASA Astrophysics Data System (ADS)

Su, Weiyi

2016-06-01

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

Algorithms For Integrating Nonlinear Differential Equations

NASA Technical Reports Server (NTRS)

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

1994-01-01

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

Effect of coumarins on HL-60 cell differentiation.

PubMed

Kawaii, S; Tomono, Y; Katase, E; Ogawa, K; Yano, M

2000-01-01

Twenty-eight coumarins, including 7 furocoumarins, were examined for their activity of induction of terminal differentiation of human promyelocytic leukemia cells (HL-60) by nitro blue tetrazolium (NBT) reducing, nonspecific esterase, specific esterase and phagocytic activities. Esculetin, nordalbergin, 6,7-dihydroxy-4-methylcoumarin and imperatorin had strong activity among the coumarins examined. HL-60 cells treated with these coumarins differentiated into mature monocyte/macrophage. The structure-activity relationship established from the results revealed that 6,7-dihydroxy moiety had an important role in the induction of differentiation of HL-60.

A Two Micron Coherent Differential Absorption Lidar Development

NASA Technical Reports Server (NTRS)

Yu, Jirong; Petros, Mulugeta; Chen, Songsheng; Bai, Yingxin; Petzar, Paul J.; Trieu, Bo C.; Koch, Grady J.; Beyon, Jeffrey Y.; VanValkenburg, Randal L.; Kavaya, Michael J.;

Brca1 regulates in vitro differentiation of mammary epithelial cells.

PubMed

Kubista, Marion; Rosner, Margit; Kubista, Ernst; Bernaschek, Gerhard; Hengstschläger, Markus

2002-07-18

Murine Brca1 is widely expressed during development in different tissues. Why alterations of BRCA1 lead specifically to breast and ovarian cancer is currently not clarified. Here we show that Brca1 protein expression is upregulated during mammary epithelial differentiation of HC11 cells, during differentiation of C2C12 myoblasts into myotubes and during neuronal differentiation of N1E-115 cells. Ectopic overexpression of BRCA1 and downregulation of endogenous Brca1 expression specifically affect the regulation of mammary epithelial cell differentiation. Accelerated mammary epithelial cell differentiation upon high ectopic BRCA1 expression is not a consequence of the anti-proliferative capacity of this tumor suppressor and independent of functional p53. Overexpression of the BRCA1 variant lacking the large central exon 11 has no effects on mammary epithelial cell differentiation. These data provide new insights into the cellular role of Brca1.

Transplantation and differentiation of donor cells in the cloned pigs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shimada, Arata; Tomii, Ryo; Kano, Koichiro

2006-06-02

The application of nuclear transfer technology is an interesting approach to investigate stem and progenitor cell transplantation therapy. If stem cells are used as a nuclear donor, donor cells can engraft into cloned animals without histocompatible problems. However, it is still uncertain whether donor cells can engraft to cloned animal and differentiate in vivo. To address this problem, we transplanted donor cells to dermal tissues of cloned pigs developed by using preadipocytes as donor cells. Preadipocytes are adipocytic progenitor which can differentiate to mature adipocytes in vitro. We showed that the donor preadipocytes were successfully transplanted into the cloned pigsmore » without immune rejection and they differentiated into mature adipocytes in vivo 3 weeks after transplantation. In contrast, allogenic control preadipocytes, which can differentiate in vitro, did not differentiate in vivo. These results indicate that donor progenitor cells can differentiate in cloned animal.« less

Apolipoprotein E promotes lipid accumulation and differentiation in human adipocytes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lasrich, Dorothee; Bartelt, Alexander; Grewal, Thomas, E-mail: thomas.grewal@sydney.edu.au

Several studies in mice indicate a role for apolipoprotein E (APOE) in lipid accumulation and adipogenic differentiation in adipose tissue. However, little is yet known if APOE functions in a similar manner in human adipocytes. This prompted us to compare lipid loading and expression of adipocyte differentiation markers in APOE-deficient and control adipocytes using the differentiated human mesenchymal stem cell line hMSC-Tert as well as primary human and mouse adipocytes as model systems. Differentiated hMSC-Tert were stably transduced with or without siRNA targeting APOE while murine adipocytes were isolated from wild type and Apoe knockout mice. Human APOE knockdown hMSC-Tertmore » adipocytes accumulated markedly less triglycerides compared to control cells. This correlated with strongly decreased gene expression levels of adipocyte markers such as adiponectin (ADIPOQ) and fatty acid binding protein 4 (FABP4) as well as the key transcription factor driving adipocyte differentiation, peroxisome proliferator activator receptor gamma (PPARG), in particular the PPARG2 isoform. Similarly, differentiation of murine Apoe-deficient adipocytes was characterized by reduced gene expression of Adipoq, Fabp4 and Pparg. Interestingly, incubation of APOE-deficient hMSC-Tert adipocytes with conditioned media from APOE3-overexpressing adipocytes or APOE-containing Very Low Density Lipoprotein (VLDL) partially restored triglyceride accumulation, but were unable to induce adipocyte differentiation, as judged by expression of adipocyte markers. Taken together, depletion of endogenous APOE in human adipocytes severely impairs lipid accumulation, which is associated with an inability to initiate differentiation. - Highlights: • Immortalized human mesenchymal stem cells were used to study adipocyte development. • Knockdown of endogenous APOE lead to impaired lipid accumulation and adipogenesis. • APOE supplementation partially restored lipid accumulation but not

The critical role of myostatin in differentiation of sheep myoblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Chenxi; Xinjiang Laboratory of Animal Biotechnology, Urumqi; Li, Wenrong

Highlights: Black-Right-Pointing-Pointer Identification of the effective and specific shRNA to knockdown MSTN. Black-Right-Pointing-Pointer Overexpression of MSTN reversibly suppressed myogenic differentiation. Black-Right-Pointing-Pointer shRNA knockdown of endogenous MSTN promoted ovine myoblast differentiation. Black-Right-Pointing-Pointer MSTN inhibits myogenic differentiation through down-regulation of MyoD and Myogenin and up-regulation of Smad3. Black-Right-Pointing-Pointer Provides a promise for the generation of transgenic sheep to improve meat productivity. -- Abstract: Myostatin [MSTN, also known as growth differentiation factor 8 (GDF8)], is an inhibitor of skeletal muscle growth. Blockade of MSTN function has been reported to result in increased muscle mass in mice. However, its role in myoblast differentiation inmore » farm animals has not been determined. In the present study, we sought to determine the role of MSTN in the differentiation of primary sheep myoblasts. We found that ectopic overexpression of MSTN resulted in lower fusion index in sheep myoblasts, which indicated the repression of myoblast differentiation. This phenotypic change was reversed by shRNA knockdown of the ectopically expressed MSTN in the cells. In contrast, shRNA knockdown of the endogenous MSTN resulted in induction of myogenic differentiation. Additional studies revealed that the induction of differentiation by knocking down the ectopically or endogenously expressed MSTN was accompanied by up-regulation of MyoD and myogenin, and down-regulation of Smad3. Our results demonstrate that MSTN plays critical role in myoblast differentiation in sheep, analogous to that in mice. This study also suggests that shRNA knockdown of MSTN could be a potentially promising approach to improve sheep muscle growth, so as to increase meat productivity.« less

Differential equations driven by rough paths with jumps

NASA Astrophysics Data System (ADS)

Friz, Peter K.; Zhang, Huilin

2018-05-01

We develop the rough path counterpart of Itô stochastic integration and differential equations driven by general semimartingales. This significantly enlarges the classes of (Itô/forward) stochastic differential equations treatable with pathwise methods. A number of applications are discussed.

Biophysical regulation of stem cell differentiation.

PubMed

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

2013-06-01

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

Antioxidants Maintain E-Cadherin Levels to Limit Drosophila Prohemocyte Differentiation

PubMed Central

Gao, Hongjuan; Wu, Xiaorong; Simon, LaTonya; Fossett, Nancy

2014-01-01

Mitochondrial reactive oxygen species (ROS) regulate a variety of biological processes by networking with signal transduction pathways to maintain homeostasis and support adaptation to stress. In this capacity, ROS have been shown to promote the differentiation of progenitor cells, including mammalian embryonic and hematopoietic stem cells and Drosophila hematopoietic progenitors (prohemocytes). However, many questions remain about how ROS alter the regulatory machinery to promote progenitor differentiation. Here, we provide evidence for the hypothesis that ROS reduce E-cadherin levels to promote Drosophila prohemocyte differentiation. Specifically, we show that knockdown of the antioxidants, Superoxide dismutatase 2 and Catalase reduce E-cadherin protein levels prior to the loss of Odd-skipped-expressing prohemocytes. Additionally, over-expression of E-cadherin limits prohemocyte differentiation resulting from paraquat-induced oxidative stress. Furthermore, two established targets of ROS, Enhancer of Polycomb and FOS, control the level of E-cadherin protein expression. Finally, we show that knockdown of either Superoxide dismutatase 2 or Catalase leads to an increase in the E-cadherin repressor, Serpent. As a result, antioxidants and targets of ROS can control E-cadherin protein levels, and over-expression of E-cadherin can ameliorate the prohemocyte response to oxidative stress. Collectively, these data strongly suggest that ROS promote differentiation by reducing E-cadherin levels. In mammalian systems, ROS promote embryonic stem cell differentiation, whereas E-cadherin blocks differentiation. However, it is not known if elevated ROS reduce E-cadherin to promote embryonic stem cell differentiation. Thus, our findings may have identified an important mechanism by which ROS promote stem/progenitor cell differentiation. PMID:25226030

Origin of igneous meteorites and differentiated asteroids

NASA Astrophysics Data System (ADS)

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

2014-07-01

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

Preserving Differential Privacy in Degree-Correlation based Graph Generation

PubMed Central

Wang, Yue; Wu, Xintao

2014-01-01

Enabling accurate analysis of social network data while preserving differential privacy has been challenging since graph features such as cluster coefficient often have high sensitivity, which is different from traditional aggregate functions (e.g., count and sum) on tabular data. In this paper, we study the problem of enforcing edge differential privacy in graph generation. The idea is to enforce differential privacy on graph model parameters learned from the original network and then generate the graphs for releasing using the graph model with the private parameters. In particular, we develop a differential privacy preserving graph generator based on the dK-graph generation model. We first derive from the original graph various parameters (i.e., degree correlations) used in the dK-graph model, then enforce edge differential privacy on the learned parameters, and finally use the dK-graph model with the perturbed parameters to generate graphs. For the 2K-graph model, we enforce the edge differential privacy by calibrating noise based on the smooth sensitivity, rather than the global sensitivity. By doing this, we achieve the strict differential privacy guarantee with smaller magnitude noise. We conduct experiments on four real networks and compare the performance of our private dK-graph models with the stochastic Kronecker graph generation model in terms of utility and privacy tradeoff. Empirical evaluations show the developed private dK-graph generation models significantly outperform the approach based on the stochastic Kronecker generation model. PMID:24723987

HOXC9-Induced Differentiation in Neuroblastoma Development

DTIC Science & Technology

2014-10-01

Neuroblastoma Development PRINCIPAL INVESTIGATOR: Han-Fei Ding RECIPIENT: Georgia Health Sciences University Research Institute, Inc... Neuroblastoma  Development   5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-12-1-0613 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S...role in determining the differentiation states of neuroblastoma tumors, with higher levels of HOXC9 promoting differentiation. At the cellular level

The Role of the Shared Family Context in Differential Parenting.

ERIC Educational Resources Information Center

Jenkins, Jennifer M.; Rasbash, Jon; O'Connor, Thomas G.

2003-01-01

This study examined role of shared family context in understanding differential parenting. Findings indicated that child age was the strongest child-specific predictor of positivity and differential positivity. Lower SES, marital dissatisfaction, and larger family size related to higher differential positivity. Children's temperament related to…

Laplace and the era of differential equations

NASA Astrophysics Data System (ADS)

Weinberger, Peter

2012-11-01

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

Transcriptional Regulation of Th17 Cell Differentiation

PubMed Central

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

2009-01-01

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

Graphene induces spontaneous cardiac differentiation in embryoid bodies

NASA Astrophysics Data System (ADS)

Ahadian, Samad; Zhou, Yuanshu; Yamada, Shukuyo; Estili, Mehdi; Liang, Xiaobin; Nakajima, Ken; Shiku, Hitoshi; Matsue, Tomokazu

2016-03-01

Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac differentiation of EBs, which has potential cell therapy and tissue regeneration applications.Graphene was embedded into the structure of mouse embryoid bodies (EBs) using the hanging drop technique. The inclusion of 0.2 mg per mL graphene in the EBs did not affect the viability of the stem cells. However, the graphene decreased the stem cell proliferation, probably by accelerating cell differentiation. The graphene also enhanced the mechanical properties and electrical conductivity of the EBs. Interestingly, the cardiac differentiation of the EB-graphene was significantly greater than that of the EBs at day 5 of culture, as confirmed by high-throughput gene analysis. Electrical stimulation (voltage, 4 V; frequency, 1 Hz; and duration, 10 ms for 2 continuous days) further enhanced the cardiac differentiation of the EBs, as demonstrated by analyses of the cardiac protein and gene expression and the beating activity of the EBs. Taken together, the results demonstrated that graphene played a major role in directing the cardiac

Muscle development and differentiation in the urodele Ambystoma mexicanum.

PubMed

Banfi, Serena; Monti, Laura; Acquati, Francesco; Tettamanti, Gianluca; de Eguileor, Magda; Grimaldi, Annalisa

2012-05-01

Muscle differentiation has been widely described in zebrafish and Xenopus, but nothing is known about this process in amphibian urodeles. Both anatomical features and locomotor activity in urodeles are known to show intermediate features between fish and anurans. Therefore, a better understanding of myogenesis in urodeles could be useful to clarify the evolutionary changes that led to the formation of skeletal muscle in the trunk of land vertebrates. We report here a detailed morphological and molecular investigation on several embryonic stages of Ambystoma mexicanum and show that the first differentiating muscle fibers are the slow ones, originating from a myoblast population initially localized close to the notochord that forms a superficial layer on the somitic surface afterwards. Subsequently, fast fibers differentiation ensues. We also identified and cloned A. mexicanum Myf5 as a muscle-specific transcriptional factor likely involved in urodele muscle differentiation. © 2012 The Authors Development, Growth & Differentiation © 2012 Japanese Society of Developmental Biologists.

Involvement of microtubules in rhizoid differentiation of Spirogyra species.

PubMed

Yoshida, K; Inoue, N; Sonobe, S; Shimmen, T

2003-06-01

Some species of Spirogyra form rosette-shaped or rod-shaped rhizoids in the terminal cell of the filaments. In the present study, we analyzed an involvement of microtubules (MTs) in rhizoid differentiation. Before rhizoid differentiation, cortical MTs were arranged transversely to the long axis of cylindrical cells, reflecting the diffuse growth. At the beginning of rhizoid differentiation, MTs were absent from the extreme tip of the terminal cell. In the other area of the cell, however, MTs were arranged transversely to the long axis of the cell. In the fully differentiated rosette-shaped rhizoid, MTs were randomly organized. However, at a younger stage of rosette-shaped rhizoids, MTs were sometimes arranged almost transversely in the lobes of the rosette. In the rod-shaped rhizoid, MTs were arranged almost transversely. MT-destabilizing drugs (oryzalin and propyzamide) induced swelling of rhizoids, and neither rosette-shaped nor rod-shaped rhizoids were formed. The role of MTs in rhizoid differentiation was discussed.

A new approach to Catalan numbers using differential equations

NASA Astrophysics Data System (ADS)

Kim, D. S.; Kim, T.

2017-10-01

In this paper, we introduce two differential equations arising from the generating function of the Catalan numbers which are `inverses' to each other in a certain sense. From these differential equations, we obtain some new and explicit identities for Catalan and higher-order Catalan numbers. In addition, by other means than differential equations, we also derive some interesting identities involving Catalan numbers which are of arithmetic and combinatorial nature.

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...

Differentiating youth who are bullied from other victims of peer-aggression: the importance of differential power and repetition.

PubMed

Ybarra, Michele L; Espelage, Dorothy L; Mitchell, Kimberly J

2014-08-01

To examine whether (1) among youth who report being bullied, differential power and repetition are useful in identifying youth who are more or less affected by the victimization experience and (2) bullying and more generalized peer aggression are distinct or overlapping constructs. Data for the Teen Health and Technology study were collected online between August 2010 and January 2011 from 3,989 13- to 18-year-olds. Data from the Growing up with Media study (Wave 3) were collected online in 2008 from 1,157 12- to 17-year-olds. In the Teen Health and Technology study, youth who reported neither differential power nor repetition had the lowest rates of interference with daily functioning. Youth who reported either differential power or repetition had higher rates, but the highest rates of interference with daily functioning were observed among youth who reported both differential power and repetition. In the Growing up with Media study, youth were victims of online generalized peer aggression (30%) or both online generalized peer aggression and cyberbullying (16%) but rarely cyberbullying alone (1%). Both differential power and repetition are key in identifying youth who are bullied and at particular risk for concurrent psychosocial challenge. Each feature needs to be measured directly. Generalized peer aggression appears to be a broader form of violence compared with bullying. It needs to be recognized that youth who are victimized but do not meet the criteria of bullying have elevated rates of problems. They are an important, albeit nonbullied, group of victimized youth to be included in research. Copyright © 2014 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.

Vascular Mural Cells Promote Noradrenergic Differentiation of Embryonic Sympathetic Neurons.

PubMed

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

2015-06-23

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

ATP synthase promotes germ cell differentiation independent of oxidative phosphorylation

PubMed Central

Teixeira, Felipe K.; Sanchez, Carlos G.; Hurd, Thomas R.; Seifert, Jessica R. K.; Czech, Benjamin; Preall, Jonathan B.; Hannon, Gregory J.; Lehmann, Ruth

2015-01-01

The differentiation of stem cells is a tightly regulated process essential for animal development and tissue homeostasis. Through this process, attainment of new identity and function is achieved by marked changes in cellular properties. Intrinsic cellular mechanisms governing stem cell differentiation remain largely unknown, in part because systematic forward genetic approaches to the problem have not been widely used1,2. Analysing genes required for germline stem cell differentiation in the Drosophila ovary, we find that the mitochondrial ATP synthase plays a critical role in this process. Unexpectedly, the ATP synthesizing function of this complex was not necessary for differentiation, as knockdown of other members of the oxidative phosphorylation system did not disrupt the process. Instead, the ATP synthase acted to promote the maturation of mitochondrial cristae during differentiation through dimerization and specific upregulation of the ATP synthase complex. Taken together, our results suggest that ATP synthase-dependent crista maturation is a key developmental process required for differentiation independent of oxidative phosphorylation. PMID:25915123

Noncommutative Differential Geometry of Generalized Weyl Algebras

NASA Astrophysics Data System (ADS)

Brzeziński, Tomasz

2016-06-01

Elements of noncommutative differential geometry of Z-graded generalized Weyl algebras A(p;q) over the ring of polynomials in two variables and their zero-degree subalgebras B(p;q), which themselves are generalized Weyl algebras over the ring of polynomials in one variable, are discussed. In particular, three classes of skew derivations of A(p;q) are constructed, and three-dimensional first-order differential calculi induced by these derivations are described. The associated integrals are computed and it is shown that the dimension of the integral space coincides with the order of the defining polynomial p(z). It is proven that the restriction of these first-order differential calculi to the calculi on B(p;q) is isomorphic to the direct sum of degree 2 and degree -2 components of A(p;q). A Dirac operator for B(p;q) is constructed from a (strong) connection with respect to this differential calculus on the (free) spinor bimodule defined as the direct sum of degree 1 and degree -1 components of A(p;q). The real structure of KO-dimension two for this Dirac operator is also described.

Bruton tyrosine kinase (Btk) suppresses osteoblastic differentiation.

PubMed

Kaneshiro, Shoichi; Ebina, Kosuke; Shi, Kenrin; Yoshida, Kiyoshi; Otsuki, Dai; Yoshikawa, Hideki; Higuchi, Chikahisa

2015-09-01

The Tec family of nonreceptor tyrosine kinases has been shown to play a key role in inflammation and bone destruction. Bruton tyrosine kinase (Btk) has been the most widely studied because of its critical role in B cells. Furthermore, recent evidence has demonstrated that blocking Btk signaling is effective in ameliorating lymphoma progression and experimental arthritis. The role of Btk in osteoblastic differentiation has not been well elucidated. In this study, we demonstrated the role of Btk in osteoblastic differentiation and investigated the effects of a Btk inhibitor on osteoblastic differentiation in mouse preosteoblastic MC3T3-E1 cells, primary calvarial osteoblasts, and bone marrow stromal ST2 cells. Btk expression was detected in all three cell lines. Btk inhibition stimulated mRNA expression of osteoblastic markers (alkaline phosphatase, osteocalcin, and osterix) and promoted mineralization of the extracellular matrix. In addition, Btk knockdown caused increased mRNA expression of osteoblastic markers. Furthermore, Btk inhibition suppressed the phosphorylation of mitogen-activated protein kinase (MAPK), nuclear factor kappa B (NFκB), and protein kinase Cα (PKCα). Our results indicate that Btk may regulate osteoblastic differentiation through the MAPK, NFκB, and PKCα signaling pathways.

In Vitro Germ Cell Differentiation from Cynomolgus Monkey Embryonic Stem Cells

PubMed Central

Yamauchi, Kaori; Hasegawa, Kouichi; Chuma, Shinichiro; Nakatsuji, Norio; Suemori, Hirofumi

2009-01-01

Background Mouse embryonic stem (ES) cells can differentiate into female and male germ cells in vitro. Primate ES cells can also differentiate into immature germ cells in vitro. However, little is known about the differentiation markers and culture conditions for in vitro germ cell differentiation from ES cells in primates. Monkey ES cells are thus considered to be a useful model to study primate gametogenesis in vitro. Therefore, in order to obtain further information on germ cell differentiation from primate ES cells, this study examined the ability of cynomolgus monkey ES cells to differentiate into germ cells in vitro. Methods and Findings To explore the differentiation markers for detecting germ cells differentiated from ES cells, the expression of various germ cell marker genes was examined in tissues and ES cells of the cynomolgus monkey (Macaca fascicularis). VASA is a valuable gene for the detection of germ cells differentiated from ES cells. An increase of VASA expression was observed when differentiation was induced in ES cells via embryoid body (EB) formation. In addition, the expression of other germ cell markers, such as NANOS and PIWIL1 genes, was also up-regulated as the EB differentiation progressed. Immunocytochemistry identified the cells expressing stage-specific embryonic antigen (SSEA) 1, OCT-4, and VASA proteins in the EBs. These cells were detected in the peripheral region of the EBs as specific cell populations, such as SSEA1-positive, OCT-4-positive cells, OCT-4-positive, VASA-positive cells, and OCT-4-negative, VASA-positive cells. Thereafter, the effect of mouse gonadal cell-conditioned medium and growth factors on germ cell differentiation from monkey ES cells was examined, and this revealed that the addition of BMP4 to differentiating ES cells increased the expression of SCP1, a meiotic marker gene. Conclusion VASA is a valuable gene for the detection of germ cells differentiated from ES cells in monkeys, and the identification and

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.

Identification of differentially expressed genes in childhood asthma.

PubMed

Zhang, Nian-Zhen; Chen, Xiu-Juan; Mu, Yu-Hua; Wang, Hewen

2018-05-01

Asthma has been the most common chronic disease in children that places a major burden for affected people and their families.An integrated analysis of microarrays studies was performed to identify differentially expressed genes (DEGs) in childhood asthma compared with normal control. We also obtained the differentially methylated genes (DMGs) in childhood asthma according to GEO. The genes that were both differentially expressed and differentially methylated were identified. Functional annotation and protein-protein interaction network construction were performed to interpret biological functions of DEGs. We performed q-RT-PCR to verify the expression of selected DEGs.One DNA methylation and 3 gene expression datasets were obtained. Four hundred forty-one DEGs and 1209 DMGs in childhood asthma were identified. Among which, 16 genes were both differentially expressed and differentially methylated in childhood asthma. Natural killer cell mediated cytotoxicity pathway, Jak-STAT signaling pathway, and Wnt signaling pathway were 3 significantly enriched pathways in childhood asthma according to our KEGG enrichment analysis. The PPI network of top 20 up- and downregulated DEGs consisted of 822 nodes and 904 edges and 2 hub proteins (UBQLN4 and MID2) were identified. The expression of 8 DEGs (GZMB, FGFBP2, CLC, TBX21, ALOX15, IL12RB2, UBQLN4) was verified by qRT-PCR and only the expression of GZMB and FGFBP2 was inconsistent with our integrated analysis.Our finding was helpful to elucidate the underlying mechanism of childhood asthma and develop new potential diagnostic biomarker and provide clues for drug design.

Identification of transcript regulatory patterns in cell differentiation.

PubMed

Gusnanto, Arief; Gosling, John Paul; Pope, Christopher

2017-10-15

Studying transcript regulatory patterns in cell differentiation is critical in understanding its complex nature of the formation and function of different cell types. This is done usually by measuring gene expression at different stages of the cell differentiation. However, if the gene expression data available are only from the mature cells, we have some challenges in identifying transcript regulatory patterns that govern the cell differentiation. We propose to exploit the information of the lineage of cell differentiation in terms of correlation structure between cell types. We assume that two different cell types that are close in the lineage will exhibit many common genes that are co-expressed relative to those that are far in the lineage. Current analysis methods tend to ignore this correlation by testing for differential expression assuming some sort of independence between cell types. We employ a Bayesian approach to estimate the posterior distribution of the mean of expression in each cell type, by taking into account the cell formation path in the lineage. This enables us to infer genes that are specific in each cell type, indicating the genes are involved in directing the cell differentiation to that particular cell type. We illustrate the method using gene expression data from a study of haematopoiesis. R codes to perform the analysis are available in http://www1.maths.leeds.ac.uk/∼arief/R/CellDiff/. a.gusnanto@leeds.ac.uk. Supplementary data are available at Bioinformatics online. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Digital differential confocal microscopy based on spatial shift transformation.

PubMed

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

2014-11-01

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

Differentiation Induces Dramatic Changes in miRNA Profile, Where Loss of Dicer Diverts Differentiating SH-SY5Y Cells Toward Senescence.

PubMed

Jauhari, Abhishek; Singh, Tanisha; Pandey, Ankita; Singh, Parul; Singh, Nishant; Srivastava, Ankur Kumar; Pant, Aditya Bhushan; Parmar, Devendra; Yadav, Sanjay

2017-09-01

MicroRNAs (miRNAs) are generated by endonuclease activity of Dicer, which also helps in loading of miRNAs to their target sequences. SH-SY5Y, a human neuroblastoma and a cellular model of neurodevelopment, consistently expresses genes related to neurodegenerative disorders at different biological levels (DNA, RNA, and proteins). Using SH-SY5Y cells, we have studied the role of Dicer and miRNAs in neuronal differentiation and explored involvement of P53, a master regulator of gene expression in differentiation-induced induction of miRNAs. Knocking down Dicer gene induced senescence in differentiating SH-SY5Y cells, which indicate the essential role of Dicer in brain development. Differentiation of SH-SY5Y cells by retinoic acid (RA) or RA + brain-derived neurotrophic factor (BDNF) induced dramatic changes in global miRNA expression. Fully differentiated SH-SY5Y cells (5-day RA followed by 3-day BDNF) significantly (p < 0.05 and atleast >3-fold change) upregulated and downregulated the expression of 77 and 17 miRNAs, respectively. Maximum increase was observed in the expression of miR-193-5p, miR-199a-5p, miR-192, miR-145, miR-28-5p, miR-29b, and miR-222 after RA exposure and miR-193-5p, miR-146a, miR-21, miR-199a-5p, miR-153, miR-29b, and miR-222 after RA + BDNF exposure in SH-SY5Y cells. Exploring the role of P53 in differentiating SH-SY5Y cells, we have observed that induction of miR-222, miR-192, and miR-145 is P53 dependent and expression of miR-193a-5p, miR-199a-5p, miR-146a, miR-21, miR-153, and miR-29b is P53 independent. In conclusion, decreased Dicer level enforces differentiating cells to senescence, and differentiating SH-SY5Y cells needs increased expression of P53 to cope up with changes in protein levels of mature neurons.

General Education Teachers' Differentiated Instruction in Elementary Inclusion

ERIC Educational Resources Information Center

Deason, Jennifer

2014-01-01

Inclusion teachers at the elementary level face challenges in differentiating instruction for all students. Despite inclusion teachers' willingness to use differentiated instruction (DI), many teachers struggle implementing DI because of teachers' understanding of DI, insufficient time for planning, and insufficient training and resources. The…

Tridax procumbens flavonoids promote osteoblast differentiation and bone formation.

PubMed

Al Mamun, Md Abdullah; Hosen, Mohammad Jakir; Islam, Kamrul; Khatun, Amina; Alam, M Masihul; Al-Bari, Md Abdul Alim

2015-11-18

Tridax procumbens flavonoids (TPFs) are well known for their medicinal properties among local natives. Besides traditionally used for dropsy, anemia, arthritis, gout, asthma, ulcer, piles, and urinary problems, it is also used in treating gastric problems, body pain, and rheumatic pains of joints. TPFs have been reported to increase osteogenic functioning in mesenchymal stem cells. Our previous study showed that TPFs were significantly suppressed the RANKL-induced differentiation of osteoclasts and bone resorption. However, the effects of TPFs to promote osteoblasts differentiation and bone formation remain unclear. TPFs were isolated from Tridax procumbens and investigated for their effects on osteoblasts differentiation and bone formation by using primary mouse calvarial osteoblasts. TPFs promoted osteoblast differentiation in a dose-dependent manner demonstrated by up-regulation of alkaline phosphatase and osteocalcin. TPFs also upregulated osteoblast differentiation related genes, including osteocalcin, osterix, and Runx2 in primary osteoblasts. TPFs treated primary osteoblast cells showed significant upregulation of bone morphogenetic proteins (BMPs) including Bmp-2, Bmp-4, and Bmp-7. Addition of noggin, a BMP specific-antagonist, inhibited TPFs induced upregulation of the osteocalcin, osterix, and Runx2. Our findings point towards the induction of osteoblast differentiation by TPFs and suggested that TPFs could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.

Stochasticity and Spatial Interaction Govern Stem Cell Differentiation Dynamics

NASA Astrophysics Data System (ADS)

Smith, Quinton; Stukalin, Evgeny; Kusuma, Sravanti; Gerecht, Sharon; Sun, Sean X.

2015-07-01

Stem cell differentiation underlies many fundamental processes such as development, tissue growth and regeneration, as well as disease progression. Understanding how stem cell differentiation is controlled in mixed cell populations is an important step in developing quantitative models of cell population dynamics. Here we focus on quantifying the role of cell-cell interactions in determining stem cell fate. Toward this, we monitor stem cell differentiation in adherent cultures on micropatterns and collect statistical cell fate data. Results show high cell fate variability and a bimodal probability distribution of stem cell fraction on small (80-140 μm diameter) micropatterns. On larger (225-500 μm diameter) micropatterns, the variability is also high but the distribution of the stem cell fraction becomes unimodal. Using a stochastic model, we analyze the differentiation dynamics and quantitatively determine the differentiation probability as a function of stem cell fraction. Results indicate that stem cells can interact and sense cellular composition in their immediate neighborhood and adjust their differentiation probability accordingly. Blocking epithelial cadherin (E-cadherin) can diminish this cell-cell contact mediated sensing. For larger micropatterns, cell motility adds a spatial dimension to the picture. Taken together, we find stochasticity and cell-cell interactions are important factors in determining cell fate in mixed cell populations.

Testing the depth-differentiation hypothesis in a deepwater octocoral

USGS Publications Warehouse

Quattrini, Andrea; Baums, Iliana B.; Shank, Timothy M.; Morrison, Cheryl L.; Cordes, Erik E.

2015-01-01

The depth-differentiation hypothesis proposes that the bathyal region is a source of genetic diversity and an area where there is a high rate of species formation. Genetic differentiation should thus occur over relatively small vertical distances, particularly along the upper continental slope (200–1000 m) where oceanography varies greatly over small differences in depth. To test whether genetic differentiation within deepwater octocorals is greater over vertical rather than geographical distances, Callogorgia delta was targeted. This species commonly occurs throughout the northern Gulf of Mexico at depths ranging from 400 to 900 m. We found significant genetic differentiation (FST = 0.042) across seven sites spanning 400 km of distance and 400 m of depth. A pattern of isolation by depth emerged, but geographical distance between sites may further limit gene flow. Water mass boundaries may serve to isolate populations across depth; however, adaptive divergence with depth is also a possible scenario. Microsatellite markers also revealed significant genetic differentiation (FST = 0.434) between C. delta and a closely related species, Callogorgia americana, demonstrating the utility of microsatellites in species delimitation of octocorals. Results provided support for the depth-differentiation hypothesis, strengthening the notion that factors covarying with depth serve as isolation mechanisms in deep-sea populations.

Precise chronology of differentiation of developing human primary dentition.

PubMed

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

2014-02-01

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

On the singular perturbations for fractional differential equation.

PubMed

Atangana, Abdon

2014-01-01

The goal of this paper is to examine the possible extension of the singular perturbation differential equation to the concept of fractional order derivative. To achieve this, we presented a review of the concept of fractional calculus. We make use of the Laplace transform operator to derive exact solution of singular perturbation fractional linear differential equations. We make use of the methodology of three analytical methods to present exact and approximate solution of the singular perturbation fractional, nonlinear, nonhomogeneous differential equation. These methods are including the regular perturbation method, the new development of the variational iteration method, and the homotopy decomposition method.

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

MicroRNA-194 promotes osteoblast differentiation via downregulating STAT1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Jun; He, Xijing; Wei, Wenzhi

Osteoblast differentiation is a vital process in maintaining bone homeostasis in which various transcriptional factors, signaling molecules, and microRNAs (miRNAs) are involved. Recently, signal transducer and activator of transcription 1 (STAT1) has been found to play an important role in regulating osteoblast differentiation. Here, we identified that STAT1 expression was regulated by miR-194. Using mouse bone mesenchymal stem cells (BMSCs), we found that miR-194 expression was significantly increased following osteoblast differentiation induction. Overexpression of miR-194 by lentivirus-mediated gene transfer markedly increased osteoblast differentiation, whereas inhibition of miR-194 significantly suppressed osteoblast differentiation of BMSCs. Using a dual-luciferase reporter assay, a directmore » interaction between miR-194 and the 3′-untranslated region (UTR) of STAT1 was confirmed. Additionally, miR-194 regulated mRNA and protein expression of STAT1 in BMSCs. Further analysis showed that miR-194 overexpression promoted the nuclear translocation of runt-related transcription factor 2 (Runx2), which is critical for osteoblast differentiation. In contrast, inhibition of miR-194 blocked the nuclear translocation of Runx2. Moreover, overexpression of STAT1 significantly blocked Runx2 nuclear translocation and osteoblast differentiation mediated by miR-194 overexpression. Taken together, our data suggest that miR-194 regulates osteoblast differentiation through modulating STAT1-mediated Runx2 nuclear translocation. - Highlights: • Overexpression of miR-194 significantly increased osteoblast differentiation. • miR-194 directly targeted the 3′- UTR of STAT1. • miR-194 regulated the expression of STAT1. • Overexpression of miR-194 promoted the nuclear translocation of Runx2.« less

Differential Equation Models for Sharp Threshold Dynamics

DTIC Science & Technology

2012-08-01

dynamics, and the Lanchester model of armed conflict, where the loss of a key capability drastically changes dynamics. We derive and demonstrate a step...dynamics using differential equations. 15. SUBJECT TERMS Differential Equations, Markov Population Process, S-I-R Epidemic, Lanchester Model 16...infection, where a detection event drastically changes dynamics, and the Lanchester model of armed conflict, where the loss of a key capability

DNA methyltransferase inhibitor CDA-II inhibits myogenic differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Zirong; Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, FL 32610; Jin, Guorong

2012-06-08

Highlights: Black-Right-Pointing-Pointer CDA-II inhibits myogenic differentiation in a dose-dependent manner. Black-Right-Pointing-Pointer CDA-II repressed expression of muscle transcription factors and structural proteins. Black-Right-Pointing-Pointer CDA-II inhibited proliferation and migration of C2C12 myoblasts. -- Abstract: CDA-II (cell differentiation agent II), isolated from healthy human urine, is a DNA methyltransferase inhibitor. Previous studies indicated that CDA-II played important roles in the regulation of cell growth and certain differentiation processes. However, it has not been determined whether CDA-II affects skeletal myogenesis. In this study, we investigated effects of CDA-II treatment on skeletal muscle progenitor cell differentiation, migration and proliferation. We found that CDA-II blocked differentiationmore » of murine myoblasts C2C12 in a dose-dependent manner. CDA-II repressed expression of muscle transcription factors, such as Myogenin and Mef2c, and structural proteins, such as myosin heavy chain (Myh3), light chain (Mylpf) and MCK. Moreover, CDA-II inhibited C1C12 cell migration and proliferation. Thus, our data provide the first evidence that CDA-II inhibits growth and differentiation of muscle progenitor cells, suggesting that the use of CDA-II might affect skeletal muscle functions.« less

SLA-aware differentiated QoS in elastic optical networks

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

Solving Differential Equations Analytically. Elementary Differential Equations. Modules and Monographs in Undergraduate Mathematics and Its Applications Project. UMAP Unit 335.

ERIC Educational Resources Information Center

Goldston, J. W.

This unit introduces analytic solutions of ordinary differential equations. The objective is to enable the student to decide whether a given function solves a given differential equation. Examples of problems from biology and chemistry are covered. Problem sets, quizzes, and a model exam are included, and answers to all items are provided. The…

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,…

Obstacles to Mathematization in Physics: The Case of the Differential

ERIC Educational Resources Information Center

López-Gay, R.; Martinez Sáez, J.; Martinez Torregrosa, J.

2015-01-01

The process of the mathematization of physical situations through differential calculus requires an understanding of the justification for and the meaning of the differential in the context of physics. In this work, four different conceptions about the differential in physics are identified and assessed according to their utility for the…

Examining Differential Math Performance by Gender and Opportunity to Learn

ERIC Educational Resources Information Center

Albano, Anthony D.; Rodriguez, Michael C.

2013-01-01

Although a substantial amount of research has been conducted on differential item functioning in testing, studies have focused on detecting differential item functioning rather than on explaining how or why it may occur. Some recent work has explored sources of differential functioning using explanatory and multilevel item response models. This…

Histone h1 depletion impairs embryonic stem cell differentiation.

PubMed

Zhang, Yunzhe; Cooke, Marissa; Panjwani, Shiraj; Cao, Kaixiang; Krauth, Beth; Ho, Po-Yi; Medrzycki, Magdalena; Berhe, Dawit T; Pan, Chenyi; McDevitt, Todd C; Fan, Yuhong

2012-01-01

Pluripotent embryonic stem cells (ESCs) are known to possess a relatively open chromatin structure; yet, despite efforts to characterize the chromatin signatures of ESCs, the role of chromatin compaction in stem cell fate and function remains elusive. Linker histone H1 is important for higher-order chromatin folding and is essential for mammalian embryogenesis. To investigate the role of H1 and chromatin compaction in stem cell pluripotency and differentiation, we examine the differentiation of embryonic stem cells that are depleted of multiple H1 subtypes. H1c/H1d/H1e triple null ESCs are more resistant to spontaneous differentiation in adherent monolayer culture upon removal of leukemia inhibitory factor. Similarly, the majority of the triple-H1 null embryoid bodies (EBs) lack morphological structures representing the three germ layers and retain gene expression signatures characteristic of undifferentiated ESCs. Furthermore, upon neural differentiation of EBs, triple-H1 null cell cultures are deficient in neurite outgrowth and lack efficient activation of neural markers. Finally, we discover that triple-H1 null embryos and EBs fail to fully repress the expression of the pluripotency genes in comparison with wild-type controls and that H1 depletion impairs DNA methylation and changes of histone marks at promoter regions necessary for efficiently silencing pluripotency gene Oct4 during stem cell differentiation and embryogenesis. In summary, we demonstrate that H1 plays a critical role in pluripotent stem cell differentiation, and our results suggest that H1 and chromatin compaction may mediate pluripotent stem cell differentiation through epigenetic repression of the pluripotency genes.

Cell Fate and Differentiation of the Developing Ocular Lens

PubMed Central

Greiling, Teri M. S.; Aose, Masamoto

2010-01-01

Purpose. Even though zebrafish development does not include the formation of a lens vesicle, the authors' hypothesis is that the processes of cell differentiation are similar in zebrafish and mammals and determine cell fates in the lens. Methods. Two-photon live embryo imaging was used to follow individual fluorescently labeled cells in real-time from the placode stage at 16 hours postfertilization (hpf) until obvious morphologic differentiation into epithelium or fiber cells had occurred at approximately 28 hpf. Immunohistochemistry was used to label proliferating, differentiating, and apoptotic cells. Results. Similar to the mammal, cells in the teleost peripheral lens placode migrated to the anterior lens mass and differentiated into an anterior epithelium. Cells in the central lens placode migrated to the posterior lens mass and differentiated into primary fiber cells. Anterior and posterior polarization in the zebrafish lens mass was similar to mammalian lens vesicle polarization. Primary fiber cell differentiation was apparent at approximately 21 hpf, before separation of the lens from the surface ectoderm, as evidenced by cell elongation, exit from the cell cycle, and expression of Zl-1, a marker for fiber differentiation. TUNEL labeling demonstrated that apoptosis was not a primary mechanism for lens separation from the surface ectoderm. Conclusions. Despite the absence of a lens vesicle in the zebrafish embryo, lens organogenesis appears to be well conserved among vertebrates. Results using three-dimensional live embryo imaging of zebrafish development showed minimal differences and strong similarities in the fate of cells in the zebrafish and mammalian lens placode. PMID:19834024

Functional differentiability in time-dependent quantum mechanics.

PubMed

Penz, Markus; Ruggenthaler, Michael

2015-03-28

In this work, we investigate the functional differentiability of the time-dependent many-body wave function and of derived quantities with respect to time-dependent potentials. For properly chosen Banach spaces of potentials and wave functions, Fréchet differentiability is proven. From this follows an estimate for the difference of two solutions to the time-dependent Schrödinger equation that evolve under the influence of different potentials. Such results can be applied directly to the one-particle density and to bounded operators, and present a rigorous formulation of non-equilibrium linear-response theory where the usual Lehmann representation of the linear-response kernel is not valid. Further, the Fréchet differentiability of the wave function provides a new route towards proving basic properties of time-dependent density-functional theory.

7 CFR 1131.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AREA Order Regulating Handling Class Prices § 1131.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2011-01-01 2011-01-01 false Adjusted Class I differentials. 1131.52 Section 1131.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1007.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AREA Order Regulating Handling Class Prices § 1007.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1007.52 Section 1007.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1033.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AREA Order Regulating Handling Class Prices § 1033.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2011-01-01 2011-01-01 false Adjusted Class I differentials. 1033.52 Section 1033.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1006.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1006.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1006.52 Section 1006.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1032.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AREA Order Regulating Handling Class Prices § 1032.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2011-01-01 2011-01-01 false Adjusted Class I differentials. 1032.52 Section 1032.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1005.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1005.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2011-01-01 2011-01-01 false Adjusted Class I differentials. 1005.52 Section 1005.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1131.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1131.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1131.52 Section 1131.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1030.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1030.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1030.52 Section 1030.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1124.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2011 CFR

2011-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1124.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2011-01-01 2011-01-01 false Adjusted Class I differentials. 1124.52 Section 1124.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1007.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1007.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1007.52 Section 1007.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1005.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1005.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1005.52 Section 1005.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1124.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1124.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1124.52 Section 1124.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1030.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1030.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1030.52 Section 1030.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1126.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AREA Order Regulating Handling Class Prices § 1126.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1126.52 Section 1126.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1005.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1005.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1005.52 Section 1005.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1124.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... MARKETING AREA Order Regulating Handling Class Prices § 1124.52 Adjusted Class I differentials. See § 1000... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1124.52 Section 1124.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1001.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1001.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1001.52 Section 1001.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1001.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AREA Order Regulating Handling Class Prices § 1001.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2012-01-01 2012-01-01 false Adjusted Class I differentials. 1001.52 Section 1001.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1032.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1032.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1032.52 Section 1032.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...

7 CFR 1033.52 - Adjusted Class I differentials.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AREA Order Regulating Handling Class Prices § 1033.52 Adjusted Class I differentials. See § 1000.52. ... 7 Agriculture 9 2013-01-01 2013-01-01 false Adjusted Class I differentials. 1033.52 Section 1033.52 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING...