Journal articles: 'DP-1'

1

Gorbet, D. W., and B. L. Tillman. "Registration of ‘DP-1’ Peanut." Journal of Plant Registrations 2, no. 3 (September 2008): 200–204. http://dx.doi.org/10.3198/jpr2007.11.0629crc.

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Darafsheh, Mohammad Reza. "CHARACTERIZATION OF THE GROUPS Dp+1(2) AND Dp+1(3) USING ORDER COMPONENTS." Journal of the Korean Mathematical Society 47, no. 2 (March 1, 2010): 311–29. http://dx.doi.org/10.4134/jkms.2010.47.2.311.

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3

Clauer, C. R., and Y. Kamide. "DP 1 and DP 2 current systems for the March 22, 1979 substorms." Journal of Geophysical Research 90, A2 (1985): 1343. http://dx.doi.org/10.1029/ja090ia02p01343.

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4

Sørensen, T. S., R. Girling, C. W. Lee, J. Gannon, L. R. Bandara, and N. B. La Thangue. "Functional interaction between DP-1 and p53." Molecular and Cellular Biology 16, no. 10 (October 1996): 5888–95. http://dx.doi.org/10.1128/mcb.16.10.5888.

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The cellular transcription factor DRTF1/E2F and the tumor suppressor protein p53 play important roles in controlling early cell cycle events. DRTF1/E2F is believed to coordinate and integrate the transcription of cell cycle-regulating genes, for example, those involved in DNA synthesis, with the activity of regulatory proteins, such as the retinoblastoma tumor suppressor gene product (pRb), which modulate its transcriptional activity. In contrast, p53 is thought to monitor the integrity of chromosomal DNA and when appropriate interfere with cell cycle progression, for example, in response to DNA damage. Generic DRTF1/E2F DNA binding activity and transcriptional activation arise when members of two distinct families of proteins, such as DP-1 and E2F-1, interact as DP/E2F heterodimers. In many cell types, DP-1 is a widespread component of DRTF1/E2F DNA binding activity which when expressed at high levels oncogenically transforms embryonic fibroblasts. Here, we document an association between DP-1 and p53 and demonstrate its presence in mammalian cell extracts. In vitro p53 interacts with an immunochemically distinct form of DP-1 and in vivo can regulate transcription driven by the DP-1/E2F-1 heterodimer. At the biochemical level, p53 competes with E2F-1 for DP-1, with a consequent reduction in DNA binding activity. Mutational analysis defines within DP-1 a C-terminal region required for the interaction with p53 and within p53 an N-terminal region distinct from that required to bind to MDM2. Our results establish DRTF1/E2F as a common cellular target in growth control mediated through the activities of pRb and p53 and suggest an alternative mechanism through which p53 may regulate cellular proliferation.

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Masuhiro, Yoshikazu, Kenichi Kayama, Akie Fukushima, Koji Baba, Makio Soutsu, Yoshiaki Kamiya, Michio Gotoh, Noboru Yamaguchi, and Shigemasa Hanazawa. "SOCS-3 Inhibits E2F/DP-1 Transcriptional Activity and Cell Cycle Progression via Interaction with DP-1." Journal of Biological Chemistry 283, no. 46 (August 7, 2008): 31575–83. http://dx.doi.org/10.1074/jbc.m800328200.

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6

SUNDELL, P. "Spin(p + 1, p + 1) COVARIANT Dp-BRANE BOUND STATES." International Journal of Modern Physics A 16, no. 17 (July 10, 2001): 3025–40. http://dx.doi.org/10.1142/s0217751x01004323.

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We construct Spin (p + 1, p + 1) covariant D p-brane bound states by using the fact that the potentials in the RR sector of toroidically compactified type II supergravity transform as a chiral spinor of the T duality group. As an application, we show the invariance of the zero-force condition for a probe D-brane under noncommutative deformations of the background, which gives a holographic proof of the stability of the corresponding field theory ground state under noncommutative deformations. We also identify the Spin (p + 1, p + 1) transformation laws by examining the covariance of the D-brane Lagrangians.

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7

Wu, C. L., M. Classon, N. Dyson, and E. Harlow. "Expression of dominant-negative mutant DP-1 blocks cell cycle progression in G1." Molecular and Cellular Biology 16, no. 7 (July 1996): 3698–706. http://dx.doi.org/10.1128/mcb.16.7.3698.

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Unregulated expression of the transcription factor E2F promotes the G1-to-S phase transition in cultured mammalian cells. However, there has been no direct evidence for an E2F requirement in this process. To demonstrate that E2F is obligatory for cell cycle progression, we attempted to inactivate E2F by overexpressing dominant-negative forms of one of its heterodimeric partners, DP-1. We dissected the functional domains of DP-1 and separated the region that facilitate heterodimer DNA binding from the E2F dimerization domain. Various DP-1 mutants were introduced into cells via transfection, and the cell cycle profile of the transfected cells was analyzed by flow cytometry. Expression of wild-type DP-1 or DP-1 mutants that bind to both DNA and E2F drove cells into S phase. In contrast, DP-1 mutants that retained E2F binding but lost DNA binding arrested cells in the G1 phase of the cell cycle. The DP-1 mutants that were unable to bind DNA resulted in transcriptionally inactive E2F complexes, suggesting that the G1 arrest is caused by formation of defective E2F heterodimers. Furthermore, the G1 arrest instigated by these DP-1 mutants could be rescued by coexpression of wild-type E2F or DP protein. These experiments define functional domains of DP and demonstrate a requirement for active E2F complexes in cell cycle progression.

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8

Li, Baojun, Yu Han, Lü Gong, and Tong Jiang. "On the Norm of the Abelian p-Group-Residuals." Mathematics 9, no. 8 (April 13, 2021): 842. http://dx.doi.org/10.3390/math9080842.

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Let G be a group. Dp(G)=⋂H≤GNG(H′(p)) is defined and, the properties of Dp(G) are investigated. It is proved that Dp(G)=P[A], where P=D(P) is the Sylow p-subgroup and A=N(A) is a Hall p′-subgroup of Dp(G), respectively. Furthermore, it is proved in a group G that (1) Dp(G)=1 if and only if CG(G′(p))=1; (2) Op′(Dp(G))≤Z∞(Op(G)) and (3) if Z(G′(p))=1, then CG(G′(p))=Dp(G).

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9

Girling, R., L. R. Bandara, E. Ormondroyd, E. W. Lam, S. Kotecha, T. Mohun, and N. B. La Thangue. "Molecular characterization of Xenopus laevis DP proteins." Molecular Biology of the Cell 5, no. 10 (October 1994): 1081–92. http://dx.doi.org/10.1091/mbc.5.10.1081.

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It is widely believed that in mammalian cells the cellular transcription factor (DRTF1/E2F integrates cell-cycle events with the transcription apparatus by interacting with important regulators of the cell cycle, such as the retinoblastoma gene product (pRb) and related proteins, cyclins, and cyclin-dependent kinases. Here, we have defined DRTF1/E2F in Xenopus laevis that, like its mammalian counterpart, specifically binds to the E2F site, is regulated during development, and interacts with pRb and related proteins. We have isolated cDNAs that encode the functional homologue of mammalian DP-1, X1 DP-1, together with a close relative, X1 DP-2. X1 DP-1, which is highly conserved with murine DP-1, is a major DNA binding component of X1 DRTF1/E2F. Both DP-1 and DP-2 synergistically interact with members of the E2F family of proteins, E2F-1, E2F-2, and E2F-3, to generate DNA binding complexes that specifically recognize the E2F site and functionally interact with E2F-1 in E2F site-dependent transcriptional activation of cellular genes. DP-1 and DP-2 encode maternally stored transcripts that are expressed during early development. In the adult however, the expression of DP-1 and DP-2 is tissue restricted. This study therefore defines a new family of transcription factors, the DP proteins, members of which can interact combinatorially with E2F proteins to generate an array of DNA binding complexes that integrate cell-cycle progression with the transcription apparatus through the E2F binding site. The tissue-specific expression of DP family members suggests that the combination of DP/E2F heterodimers that constitute DRTF1/E2F is influenced by the phenotype of the cell.

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10

Hiebert, S. W., G. Packham, D. K. Strom, R. Haffner, M. Oren, G. Zambetti, and J. L. Cleveland. "E2F-1:DP-1 induces p53 and overrides survival factors to trigger apoptosis." Molecular and Cellular Biology 15, no. 12 (December 1995): 6864–74. http://dx.doi.org/10.1128/mcb.15.12.6864.

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The E2F DNA binding activity consists of a heterodimer between E2F and DP family proteins, and these interactions are required for association of E2F proteins with pRb and the pRb-related proteins p107 and p130, which modulate E2F transcriptional activities. E2F-1 expression is sufficient to release fibroblasts from G0 and induce entry into S phase, yet it also initiates apoptosis. To investigate the mechanisms of E2F-induced apoptosis, we utilized interleukin-3 (IL-3)-dependent 32D.3 myeloid cells, a model of hematopoietic progenitor programmed cell death. In the absence of IL-3, E2F-1 alone was sufficient to induce apoptosis, and p53 levels were diminished. DP-1 alone was not sufficient to induce cell cycle progression or alter rates of death following IL-3 withdrawal. However, overexpression of both E2F-1 and DP-1 led to the rapid death of cells even in the presence of survival factors. In the presence of IL-3, levels of endogenous wild-type p53 increased in response to E2F-1, and coexpression of DP-1 further augmented p53 levels. These results provide evidence that E2F is a functional link between the tumor suppressors p53 and pRb. However, induction of p53 alone was not sufficient to trigger apoptosis, suggesting that the ability of E2F to override survival factors involves additional effectors.

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11

Tao, Y., R. F. Kassatly, W. D. Cress, and J. M. Horowitz. "Subunit composition determines E2F DNA-binding site specificity." Molecular and Cellular Biology 17, no. 12 (December 1997): 6994–7007. http://dx.doi.org/10.1128/mcb.17.12.6994.

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The product of the retinoblastoma (Rb) susceptibility gene, Rb-1, regulates the activity of a wide variety of transcription factors, such as E2F, in a cell cycle-dependent fashion. E2F is a heterodimeric transcription factor composed of two subunits each encoded by one of two related gene families, denoted E2F and DP. Five E2F genes, E2F-1 through E2F-5, and two DP genes, DP-1 and DP-2, have been isolated from mammals, and heterodimeric complexes of these proteins are expressed in most, if not all, vertebrate cells. It is not yet clear whether E2F/DP complexes regulate overlapping and/or specific cellular genes. Moreover, little is known about whether Rb regulates all or a subset of E2F-dependent genes. Using recombinant E2F, DP, and Rb proteins prepared in baculovirus-infected cells and a repetitive immunoprecipitation-PCR procedure (CASTing), we have identified consensus DNA-binding sites for E2F-1/DP-1, E2F-1/DP-2, E2F-4/DP-1, and E2F-4/DP-2 complexes as well as an Rb/E2F-1/DP-1 trimeric complex. Our data indicate that (i) E2F, DP, and Rb proteins each influence the selection of E2F-binding sites; (ii) E2F sites differ with respect to their intrinsic DNA-bending properties; (iii) E2F/DP complexes induce distinct degrees of DNA bending; and (iv) complex-specific E2F sites selected in vitro function distinctly as regulators of cell cycle-dependent transcription in vivo. These data indicate that the specific sequence of an E2F site may determine its role in transcriptional regulation and suggest that Rb/E2F complexes may regulate subsets of E2F-dependent cellular genes.

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12

Gramatikov, Pavlin, Roumen Nedkov, and Georgi Stanev. "Secondary power supply system for spacecraft potential monitor DP-1 and DP-2, "OBSTANOVKA" project, International Space Station." Aerospace Research in Bulgaria 31 (2019): 108–16. http://dx.doi.org/10.3897/arb.v31.e09.

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Plasma Wave Complex is a scientific instrumentation for wave parameters measurements in the ISS environment, and is implemented in the OBSTANOVKA experiment on board of Russian segment of ISS. The device Spacecraft Potential monitor „DP-1“and „DP-2“(one part of Plasma-Wave Complex) was developed in IKI BAS and measured the potential of the hull no more than 3 m from the surface of the ISS at range +/–200 V; 0to 500 Hz. There are block and functional diagrams of the "DP" and the secondary power supply system, designed to supply the measuring probe, analogue and digital circuit boards. The secondary power supply system for the device „DP-1“and „DP-2“is discussed herein detail.

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13

Turbina, Lidia Grigor'evna, Sergey Alexandrovich Gordeev, and Anna Aronovna Zus'man. "Antidepressant therapy in complex treatment of painful diabetic polyneuropathy." Diabetes mellitus 15, no. 3 (September 15, 2012): 67–73. http://dx.doi.org/10.14341/2072-0351-6088.

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Aims. Comparative efficiency and safety analysis of antidepressant agents from different pharmacological classes (pipofezine and venlafaxine)in combination with carbamazepine for treatment of neuropathic pain (NP) in patients with diabetic polyneuropathy (DP). Materials and methods. We examined 21 male and 27 female patients with painful DP (mean age 54.3?14.2 years; mean duration ofdiabetes mellitus (DM) 8.9?5.1 years; mean duration of DP - 3.8?2.1 years). DP was diagnosed clinically and by electromyographymethod. Pain syndrome was assessed with DN4 questionnaire, visual analogue scale (VAS) and McGill Pain Questionnaire. Psycho-vegetative status was evaluated by Spielberger test with reactive and personal anxiety (RA and PA) assessment and Beck depressioninventory. All patients received symptomatic pharmacotherapy with anticonvulsant and antidepressant agent. First group (DP-1)included 23 patients on carbamazepin and pipofezine. Second group (DP-2) included 25 patients on carbamazepin and venlafaxine. Results. Following treatment, pain syndrome was completely compensated in 8.7% of patients from DP-1 group and 12.5% from DP-2.Decrease in pain intensity?50% from initial level was achieved in 73.9% (DP-1) and 75% (DP-2) of cases. Mean pain intensityaccording to VAS reduced from 5.2?2.1 points to 2.3?1.4 points (DP-1) and from 5.8?2.3 points (DP-2) with equal statistical significance(p

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14

Steinbrink, Claudia, Simone Schwanda, Maria Klatte, and Thomas Lachmann. "Sagen Wahrnehmungsleistungen zu Beginn der Schulzeit den Lese-Rechtschreiberfolg in Klasse 1 und 2 voraus?" Zeitschrift für Entwicklungspsychologie und Pädagogische Psychologie 42, no. 4 (October 2010): 188–200. http://dx.doi.org/10.1026/0049-8637/a000023.

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Zusammenfassung. Die Studie überprüft die Validität der Differenzierungsproben (DP) 1 und 2 ( Breuer & Weuffen, 2006 ) bezüglich der Vorhersage von Lese-Rechtschreibschwierigkeiten am Ende von Klasse 1 und 2. Kinder mit deutscher Muttersprache wurden zu Beginn von Klasse 1 mit der DP 1 und in der Mitte von Klasse 1 mit der DP 2 getestet. Die Leistungen in den DP klären zwischen 3 und 9% der Varianz im späteren Lesen und Schreiben auf. Bei Einbeziehung zusätzlicher Prädiktoren erhöht sich die aufgeklärte Varianz. Es setzen sich aber andere Variablen, insbesondere IQ und vorschulische Lese-Rechtschreibfähigkeit als wichtigere Prädiktoren durch. Die klassifikatorischen Güteindizes Prädiktortrefferquote, Sensitivität und RATZ-Index liegen überwiegend im inakzeptablen Bereich. Somit ist die prognostische Validität von DP 1 und DP 2 als unzureichend zu bewerten. Die im Vergleich zu anderen Screeningverfahren geringere Validität wird auch im Zusammenhang mit Unterschieden hinsichtlich des Einschlusses von Kindern mit nicht-deutscher Muttersprache diskutiert.

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Pelka, P., M. S. Miller, M. Cecchini, A. F. Yousef, D. M. Bowdish, F. Dick, P. Whyte, and J. S. Mymryk. "Adenovirus E1A Directly Targets the E2F/DP-1 Complex." Journal of Virology 85, no. 17 (June 29, 2011): 8841–51. http://dx.doi.org/10.1128/jvi.00539-11.

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16

Magae, J., C. L. Wu, S. Illenye, E. Harlow, and N. H. Heintz. "Nuclear localization of DP and E2F transcription factors by heterodimeric partners and retinoblastoma protein family members." Journal of Cell Science 109, no. 7 (July 1, 1996): 1717–26. http://dx.doi.org/10.1242/jcs.109.7.1717.

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E2F is a family of transcription factors implicated in the regulation of genes required for progression through G1 and entry into the S phase. The transcriptionally active forms of E2F are heterodimers composed of one polypeptide encoded by the E2F gene family and one polypeptide encoded by the DP gene family. The transcriptional activity of E2F/DP heterodimers is influenced by association with the members of the retinoblastoma tumor suppressor protein family (pRb, p107, and p130). Here the intracellular distribution of E2F and DP proteins was investigated in transiently transfected Chinese hamster and human cells. In transfected cells, DP-1 did not accumulate in the nucleus unless it was coexpressed with the heterodimeric partners E2F-1, E2F-2, or E2F-3. Domain mapping experiments showed that regions of E2F-1 and DP-1 that are required for stable association of the two proteins were also required for nuclear localization of DP-1. Unlike E2F-1, -2, and -3, E2F-4 did not accumulate in the nucleus unless it was coexpressed with DP-2, p107 and p130, but not pRb, stimulated nuclear localization of E2F-4, either alone or in combination with DP-2. These results indicate that DP proteins preferentially associate with specific E2F partners, and suggest that the ability of specific E2F/DP heterodimers to localize in the nucleus contributes to the regulation of E2F activity.

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17

Hendges, Vanessa Maria, Magali Teresinha Quevedo Grave, and Eduardo Périco. "Avaliação do desenvolvimento psicomotor de crianças com Síndrome de Down." Revista Neurociências 29 (January 4, 2021): 1–26. http://dx.doi.org/10.34024/rnc.2021.v29.10907.

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Introdução. A Síndrome de Down (SD) é uma alteração genética que ocorre devido à trissomia do cromossomo 21. Além do fenótipo característico, há hipotonia muscular generalizada, deficiência intelectual e atraso no desenvolvimento psicomotor (DPM). Objetivo. Verificar o DPM de crianças com SD, de até 42 meses, considerando os domínios cognitivo, de linguagem e motor. Método. Estudo exploratório, descritivo, transversal, de abordagem quantitativa, no qual participaram 13 crianças com idades entre 10 e 40 meses, avaliadas através da Escala de desenvolvimento Bayley III. Resultados. A pontuação escalonada demonstra que na área cognitiva, 12 crianças estão a 1 DP (desvio padrão) abaixo da média e uma criança está entre 1 e 2 DP abaixo da média; na comunicação receptiva uma criança está na média, 10 crianças estão a 1 DP abaixo da média e duas crianças estão entre 1 e 2 DP abaixo da média; na comunicação expressiva uma criança está na média, cinco crianças estão a 1 DP abaixo da média e sete estão entre 1 e 2 DP abaixo da média. Na motricidade fina, uma criança está na média e 12 estão a 1 DP abaixo da média; na motricidade grossa há duas crianças a 1 DP abaixo da média, 9 crianças entre 1 e 2 DP abaixo da média e duas crianças entre 2 e 3 DP abaixo da média. Conclusão. As crianças apresentam atraso em todas as áreas do DPM, quando comparadas com crianças típicas e as áreas mais defasadas são a motricidade grossa e a comunicação expressiva.

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18

Magae, Junji, Sharon Illenye, Young-Chae Chang, Youji Mitsui, and Nicholas H. Heintz. "Association with E2F-1 governs intracellular trafficking and polyubiquitination of DP-1." Oncogene 18, no. 3 (January 1999): 593–605. http://dx.doi.org/10.1038/sj.onc.1202345.

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19

Mutha, V. V. S. R. N. Anji Karun, Chakravarthy Chandra, B. Vijayabhaskar, Prabhakar S. Achanta, Jagadeesh Narkedimilli, Muralidharan Kaliyaperumal, Raghu Babu Korupolu, Susheela Bai Gajbhiye, and Chidananda Swamy Rumalla. "Separation of Unprecedented Degradants of Domperidone by Ultra-Performance Convergence Chromatography and Their Structure Elucidation." Journal of Chromatographic Science 57, no. 9 (September 3, 2019): 806–14. http://dx.doi.org/10.1093/chromsci/bmz066.

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Abstract Domperidone, a gastroprokinetic agent, is a common drug to treat emesis. It was subjected to acid, base-mediated hydrolysis, peroxide-mediated oxidation, photolysis and thermal degradation according to ICH guidelines to observe stability of the selected drug under the stress conditions. Although the drug is resistant to base hydrolysis, photolysis and thermal stressors, two degradants (DP-ISO1 and DP-ISO2) were formed in acid mediated hydrolysis. Oxidation with hydrogen peroxide also resulted in one product (DP-OX). All three degradants were isolated from the crude reaction mixture by preparative high-performance liquid chromatography and supercritical fluid chromatography. Structures of isolated compounds were unambiguously characterized as 5-chloro-1-(1-(3-(6-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidin-4-yl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO1), 5-chloro-1-(3-(4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)piperidin-1-yl)propyl)-1,3-dihydro-2H-benzo[d]imidazol-2-one (DP-ISO2), 4-(5-chloro-2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)-1-(3-(2-oxo-2,3-dihydro-1H-benzo[d]imidazol-1-yl)propyl)piperidine 1-oxide (DP-OX) by analysis of mass spectrometry, 1D and 2D nuclear magnetic resonance spectra. To the best of our knowledge, DP-ISO1 and DP-ISO2 are new and DP-OX was previously reported as domperidone impurity.

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Rincon, M., and R. A. Flavell. "Regulation of AP-1 and NFAT transcription factors during thymic selection of T cells." Molecular and Cellular Biology 16, no. 3 (March 1996): 1074–84. http://dx.doi.org/10.1128/mcb.16.3.1074.

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The ability of thymocytes to express cytokine genes changes during the different stages of thymic development. Although CD4- CD8- thymocytes are able to produce a wide spectrum of cytokines in response to a T-cell receptor (TcR)-independent stimulus, as they approach the double-positive (DP) CD4+ CD8+ stage, they lose the ability to produce cytokine. After the DP stage, thymocytes become single-positive CD4+ or CD8+ thymocytes which reacquire the ability to secrete cytokines. In an attempt to understand the molecular basis of this specific regulatin, we use AP-1-luciferase and newly generated NFAT-luciferase transgenic mice to analyze the transcriptional and DNA-binding activities of these two transcription factors that are involved in the regulation of cytokine gene expression. Here, we show that both AP-1 and NFAT transcriptional activities are not inducible in the majority of DP cells but that during the differentiation of DP cells to the mature single-positive stage, thymocytes regain this inducibility. Subpopulation analysis demonstrates that this inducibility is reacquired at the DP stage before the down-modulation of one of the coreceptors. Indeed AP-1 inducibility, just like the ability to express the interleukin-2 gene, is reacquired during the differentiation of DP TcRlow CD69low heat-stable antigen (HSA)high thymocytes to DP TcRhigh CD69high HSAhigh cells, which is considered to be the consequence of the first signal that initiates positive selection. We therefore propose that the inability of DP thymocytes to induce AP-1 and NFAT activities is one of the causes for the lack of cytokine gene expression at this stage and that this inducibility is reacquired at the latest stage of DP differentiation as a consequence of positive selection. This could be a mechanism to prevent the activation of DP thymocytes before selection has taken place.

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21

Ribeiro, Euler Esteves, Ivana Beatrice Manica da Cruz, Rodolfo Schneider, and Antonio Carlos de Araújo Souza. "Prevalência de desvios-padrão determinados pela ultra-sonometria de calcâneo e sua associação com índice de massa corporal e idade em mulheres pós-menopáusicas residentes em Manaus-AM." Revista Brasileira de Geriatria e Gerontologia 9, no. 3 (September 2006): 7–22. http://dx.doi.org/10.1590/1809-9823.2006.09032.

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Resumo O envelhecimento populacional aumenta o número de idosos e a prevalência de doenças como osteoporose, que está associada a fraturas. Para esse tipo de avaliação, a ultra-sonometria de calcâneo (USO) poderia ser uma boa alternativa, porque é barata, fácil de ser medida e não expõe os indivíduos à radiação. O estudo apresentado estimou a prevalência de três diferentes grupos de desvio-padrão (DP<-1, DP<-1<-2,5 e DP<-2,5), determinados pela USO e sua associação com idade e índice de massa corporal (IMC) em mulheres idosas que vivem na comunidade de Manaus-AM. O delineamento foi do tipo retrospectivo, observacional e descritivo, em 997 mulheres que fizeram o exame de USO de calcâneo e foram classificadas nos três grupos (DP <-2,5, SD >-1<-2,5DP e SD <-1). A prevalência dos grupos DP foi: DP<-2,5 = 23,0% (229), DP<-1<2,5 = 53,2% (530) e DP<-2,5 = 23,6% (238). Mulheres com DP<-2,5 apresentaram valores de IMC significativamente mais baixos (p=0,016) e também idade mais elevada (p=0,007). Os resultados sugerem associação da USO com IMC e idade avançada, corroborando estudos previamente publicados na literatura. O estudo corrobora a possibilidade de utilização da USO em levantamentos epidemiológicos.

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22

Weninger, Bernhard Paul. "Niche Construction and Theory of Agricultural Origins. Case studies in punctuated equilibrium." Documenta Praehistorica 44 (January 3, 2018): 6. http://dx.doi.org/10.4312/dp.1.

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In contemporary archaeological and anthropological research, the domestication of plants and animals in the Near East during the Early Holocene is alternatively interpreted as an overall slow and gradual, or as a rapid process. The present reanalysis of published archaeobotanical and archaeozoological data shows that the wild-domesticate-transition (WDT) was indeed initially slow (millennial scale), but terminated at 10.2 ± 0.2 ka cal BP with an abrupt switch to herding and agriculture. The abruptness of WDT can be understood as due to amplification under positive feedback conditions (resonance) of some few biological and social factors, primarily the short and long- distance transport of domesticates, in conjunction with a synchronous, abrupt climatic switch to higher precipitation.

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Yu, Qing, Jung-Hyun Park, Loretta L. Doan, Batu Erman, Lionel Feigenbaum, and Alfred Singer. "Cytokine signal transduction is suppressed in preselection double-positive thymocytes and restored by positive selection." Journal of Experimental Medicine 203, no. 1 (January 3, 2006): 165–75. http://dx.doi.org/10.1084/jem.20051836.

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Death by neglect requires that CD4+8+ double-positive (DP) thymocytes avoid cytokine-mediated survival signals, which is presumably why DP thymocytes normally extinguish IL-7R gene expression. We report that DP thymocytes before positive selection (preselection DP thymocytes) fail to transduce IL-7 signals even when they express high levels of transgenic IL-7R on their surface, because IL-7R signal transduction is actively suppressed in preselection DP thymocytes by suppressor of cytokine signaling (SOCS)–1. SOCS-1 is highly expressed in preselection DP thymocytes, but it is down-regulated by T cell receptor–mediated positive selection signals. Interestingly, we found that the uniquely small cell volume of DP thymocytes is largely the result of absent IL-7 signaling in preselection DP thymocytes. We also report that, contrary to current concepts, preselection DP thymocytes express high levels of endogenously encoded IL-4Rs. However, their ability to transduce cytokine signals is similarly suppressed by SOCS-1. Thus, despite high surface expression of transgenic or endogenous cytokine receptors, cytokine signal transduction is actively suppressed in preselection DP thymocytes until it is restored by positive selection.

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Saban, Yves, and Sylvie de Salvador. "Guidelines for Dorsum Preservation in Primary Rhinoplasty." Facial Plastic Surgery 37, no. 01 (February 2021): 053–64. http://dx.doi.org/10.1055/s-0041-1723827.

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AbstractThe multiplication of scientific articles related to the fast-growing interest in preservation rhinoplasty (PR) may lead to confusion in the decision-making process, thus requiring a need for guidelines through a focus on benefit–risk ratio and revisions. This study analyzes a 352 consecutive primary rhinoplasties series during a 3 year (2016 to 2019) period with 1-year follow-up. The evaluation of the most appropriate procedure to the patient's nasal anatomy and expectations requires to correlate (1) a convenient classification of nasal profile lines; (2) a review of the dorsum preservation techniques (DP) classified as: full DP, DP + resurfacing, bony cartilaginous disarticulation, and finally traditional rhinoplasty; (3) the role of septoplasties, subdividing this series in two main groups; (4) analyzing the revisions in the different subgroups and to the literature. Thirty-five revisions (9.94%) were done. Correlations between profile lines, surgical procedures, and revisions show (1) 129 straight noses underwent full DP in 88 cases with 5.68% revisions; however, DP+ hump resurfacing in 32 patients with no revision. (2) Among 71 tension noses, 33 underwent full DP with 6 revisions (18.18%), while 32 patients had bony cap resurfacing, 1 revision (3.13%). (3) Among 109 kyphotic noses, 64 patients underwent DP + resurfacing with 10 revisions (15.63%); 27 patients had cartilage-only DP with two revisions (7.41%). (4) In the 43 difficult noses group, revisions were done equally in DP + resurfacing and cartilage-only subgroups. Septum stability modifies the correlations, introducing Cottle's septorhinoplasty in the paradigm. The revision rate is jumping ×2.50% when a septoplasty is associated with the rhinoplasty. Correlated to the benefit–risk ratio and the revisions, the following guidelines may be suggested in primary rhinoplasty: (1) Straight noses: full DP, (2) tension noses: DP + dorsum resurfacing and/or Cottle's variations, (3) kyphotic noses: cartilage-only DP, and (4) difficult noses: traditional rhinoplasties.

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Mostafa, Gamal Abdel Hafiz, Mohamed Hefnawy, and Abdulrahman Al-Majed. "Membrane Sensors for the Selective Determination of Donepezil Hydrochloride." Journal of AOAC INTERNATIONAL 93, no. 2 (April 1, 2010): 549–55. http://dx.doi.org/10.1093/jaoac/93.2.549.

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Abstract The construction and electrochemical response characteristics of polyvinylchloride (PVC) membrane sensors for donepezil HCl (DP) are described. The sensing membranes incorporated ion-association complexes of DP cation and sodium tetraphenyl borate (sensor 1), phosphomolybdic acid (sensor 2), or phosphotungstic acid (sensor 3) as electroactive materials. The sensors displayed a fast, stable, and near-Nernstian response over a relatively wide DP concentration range (1 102 to 1 106 M), with cationic slopes of 53.0, 54.0, and 51.0 mV/ concentration decade over a pH range of 4.0 to 8.0. The sensors showed good discrimination of DP from several inorganic and organic compounds. The direct determination of 2.54000.0 g/mL DP showed average recoveries of 99.0, 99.5, and 98.5, and mean RSDs of 1.6, 1.5, and 1.7 at 100.0 g/mL for sensors 1, 2, and 3, respectively. The proposed sensors have been applied for direct determination of DP in two pharmaceutical preparations. The results obtained for determination of DP in tablets using the proposed sensors compared favorably with those obtained using an HPLC method. The sensors have been used as indicator electrodes for potentiometric titration of DP.

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Shih, Ming Chi, Edson Amaro Jr, Henrique Ballalai Ferraz, Marcelo Queiroz Hoexter, Fabricio Oliveira Goulart, Jairo Wagner, Li Fu Lin, et al. "Neuroimagem do transportador de dopamina na doença de Parkinson: primeiro estudo com [99mTc]-TRODAT-1 e SPECT no Brasil." Arquivos de Neuro-Psiquiatria 64, no. 3a (September 2006): 628–34. http://dx.doi.org/10.1590/s0004-282x2006000400021.

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INTRODUÇÃO: Radiotraçadores para neuroimagem de transportador de dopamina (TDA) foram desenvolvidos para estimar a perda de neurônios dopaminérgicos in vivo na doença de Parkinson (DP). OBJETIVO: Avaliar a densidade de TDA in vivo utilizando [99mTc]-TRODAT-1 (INER-Taiwan) e SPECT em uma população de pacientes brasileiros com DP. MÉTODO: Quinze pacientes com DP e 15 controles saudáveis pareados realizaram exames de SPECT com [99mTc]-TRODAT-1 (INER-Taiwan). Estimativas da densidade de TDA estriatal foram calculadas usando potencial de ligação (PL). Pacientes foram avaliados com escalas para PD. RESULTADOS: Pacientes com DP apresentaram redução significativa do PL-TDA (0,38±0,12) comparado aos controles (0,84±0,16, p<0,01). Foi possível discriminar casos de DP de controles com uma sensibilidade de 100% e especificidade de 100%. Foram obtidas correlações negativas entre PL-TDA e escalas de severidade da DP (rho= -0,7, p<0,001) e disfunção motora (rho= -0,8, p<0,001). CONCLUSÃO: Exames de SPECT com [99mTc]-TRODAT-1 foram capazes de discriminar pacientes com DP de controles. Esta técnica é um instrumento útil para medir a densidade de TDA e pode ser utilizado para clínica e pesquisa no Brasil.

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Xu, M., K. A. Sheppard, C. Y. Peng, A. S. Yee, and H. Piwnica-Worms. "Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation." Molecular and Cellular Biology 14, no. 12 (December 1994): 8420–31. http://dx.doi.org/10.1128/mcb.14.12.8420.

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E2F-1, a member of the E2F transcription factor family, contributes to the regulation of the G1-to-S phase transition in higher eukaryotic cells. E2F-1 forms a heterodimer with DP-1 and binds to several cell cycle regulatory proteins, including the retinoblastoma family (RB, p107, p130) and cyclin A/CDK2 complexes. We have analyzed E2F-1 phosphorylation and its interaction with cyclin A/CDK2 complexes both in vivo and in vitro. In vitro, E2F-1 formed a stable complex with cyclin A/CDK2 but not with either subunit alone. DP-1 did not interact with cyclin A, CDK2, or the cyclin A/CDK2 complex. While the complex of cyclin A/CDK2 was required for stable complex formation with E2F-1, the kinase-active form of CDK2 was not required. However, E2F-1 was phosphorylated by cyclin A/CDK2 in vitro and was phosphorylated in vivo in HeLa cells. Two-dimensional tryptic phosphopeptide mapping studies demonstrated an overlap in the phosphopeptides derived from E2F-1 labeled in vitro and in vivo, indicating that cyclin A/CDK2 may be responsible for the majority of E2F-1 phosphorylation in vivo. Furthermore, an active DNA-binding complex could be reconstituted from purified E2F-1/DP-1 and cyclin A/CDK2. Binding studies conducted both in vitro and in vivo demonstrated that the cyclin A/CDK2-binding region resided within the N-terminal 124 amino acids of E2F-1. Because the stable association of E2F-1 with cyclin A/CDK2 in vitro and in vivo did not require a DP-1- or RB-binding domain and because the interactions could be reconstituted from purified components in vitro, we conclude that the interactions between cyclin A/CDK2 and E2F-1 are direct. Finally, we report that the DNA-binding activity of the E2F-1/DP-1 complex is inhibited following phosphorylation by cyclin A/CDK2.

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Xu, M., K. A. Sheppard, C. Y. Peng, A. S. Yee, and H. Piwnica-Worms. "Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation." Molecular and Cellular Biology 14, no. 12 (December 1994): 8420–31. http://dx.doi.org/10.1128/mcb.14.12.8420-8431.1994.

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E2F-1, a member of the E2F transcription factor family, contributes to the regulation of the G1-to-S phase transition in higher eukaryotic cells. E2F-1 forms a heterodimer with DP-1 and binds to several cell cycle regulatory proteins, including the retinoblastoma family (RB, p107, p130) and cyclin A/CDK2 complexes. We have analyzed E2F-1 phosphorylation and its interaction with cyclin A/CDK2 complexes both in vivo and in vitro. In vitro, E2F-1 formed a stable complex with cyclin A/CDK2 but not with either subunit alone. DP-1 did not interact with cyclin A, CDK2, or the cyclin A/CDK2 complex. While the complex of cyclin A/CDK2 was required for stable complex formation with E2F-1, the kinase-active form of CDK2 was not required. However, E2F-1 was phosphorylated by cyclin A/CDK2 in vitro and was phosphorylated in vivo in HeLa cells. Two-dimensional tryptic phosphopeptide mapping studies demonstrated an overlap in the phosphopeptides derived from E2F-1 labeled in vitro and in vivo, indicating that cyclin A/CDK2 may be responsible for the majority of E2F-1 phosphorylation in vivo. Furthermore, an active DNA-binding complex could be reconstituted from purified E2F-1/DP-1 and cyclin A/CDK2. Binding studies conducted both in vitro and in vivo demonstrated that the cyclin A/CDK2-binding region resided within the N-terminal 124 amino acids of E2F-1. Because the stable association of E2F-1 with cyclin A/CDK2 in vitro and in vivo did not require a DP-1- or RB-binding domain and because the interactions could be reconstituted from purified components in vitro, we conclude that the interactions between cyclin A/CDK2 and E2F-1 are direct. Finally, we report that the DNA-binding activity of the E2F-1/DP-1 complex is inhibited following phosphorylation by cyclin A/CDK2.

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Albrecht, Lauren V., Lichao Zhang, Jeffrey Shabanowitz, Enkhsaikhan Purevjav, Jeffrey A. Towbin, Donald F. Hunt, and Kathleen J. Green. "GSK3- and PRMT-1–dependent modifications of desmoplakin control desmoplakin–cytoskeleton dynamics." Journal of Cell Biology 208, no. 5 (March 2, 2015): 597–612. http://dx.doi.org/10.1083/jcb.201406020.

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Intermediate filament (IF) attachment to intercellular junctions is required for skin and heart integrity, but how the strength and dynamics of this attachment are modulated during normal and pathological remodeling is poorly understood. We show that glycogen synthase kinase 3 (GSK3) and protein arginine methyltransferase 1 (PRMT-1) cooperate to orchestrate a series of posttranslational modifications on the IF-anchoring protein desmoplakin (DP) that play an essential role in coordinating cytoskeletal dynamics and cellular adhesion. Front-end electron transfer dissociation mass spectrometry analyses of DP revealed six novel serine phosphorylation sites dependent on GSK3 signaling and four novel arginine methylation sites including R2834, the mutation of which has been associated with arrhythmogenic cardiomyopathy (AC). Inhibition of GSK3 or PRMT-1 or overexpression of the AC-associated mutant R2834H enhanced DP–IF associations and delayed junction assembly. R2834H blocked the GSK3 phosphorylation cascade and reduced DP–GSK3 interactions in cultured keratinocytes and in the hearts of transgenic R2834H DP mice. Interference with this regulatory machinery may contribute to skin and heart diseases.

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Tarao, Mitsunori, and Masayuki Seto. "Estimation of the Yield Coefficient ofPseudomonas sp. Strain DP-4 with a Low Substrate (2,4-Dichlorophenol [DCP]) Concentration in a Mineral Medium from Which Uncharacterized Organic Compounds Were Eliminated by a Non-DCP-Degrading Organism." Applied and Environmental Microbiology 66, no. 2 (February 1, 2000): 566–70. http://dx.doi.org/10.1128/aem.66.2.566-570.2000.

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ABSTRACT The yield coefficient (YC) of Pseudomonas sp. strain DP-4, a 2,4-dichlorophenol (DCP)-degrading organism, was estimated from the number of CFU produced at the expense of 1 unit amount of DCP at low concentrations. At a low concentration of DCP, the YC can be overestimated in pure culture, because DP-4 assimilated not only DCP but also uncharacterized organic compounds contaminating a mineral salt medium. The concentration of these uncharacterized organic compounds was nutritionally equivalent to 0.7 μg of DCP-C ml−1. A mixed culture with non-DCP-degrading organisms resulted in elimination of ca. 99.9% of the uncharacterized organic compounds, and then DP-4 assimilated only DCP as a substrate. In a mixed culture, DP-4 degraded an initial concentration of 0.1 to 10 μg of C ml of DCP−1 and the number of CFU of DP-4 increased. In the mixed culture, DCP at an initial concentration of 0.07 μg of C ml−1 was degraded. However, the number of CFU of DP-4 did not increase. DCP at an extremely low initial concentration of 0.01 μg of C ml−1 was not degraded in mixed culture even by a high density, 105 CFU ml−1, of DP-4. When glucose was added to this mixed culture to a final concentration of 1 μg of C ml−1, the initial concentration of 0.01 μg of C ml of DCP−1 was degraded. These results suggested that DP-4 required cosubstrates to degrade DCP at an extremely low initial concentration of 0.01 μg of C ml−1. The YCs of DP-4 at the expense of DCP alone decreased discontinuously with the decrease of the initial concentration of DCP, i.e., 1.5, 0.19, or 0 CFU per pg of DCP-C when 0.7 to 10, 0.1 to 0.5, or 0.07 μg of C ml of DCP−1 was degraded, respectively. In this study, we developed a new method to eliminate uncharacterized organic compounds, and we estimated the YC of DP-4 at the expense of DCP as a sole source of carbon.

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Ishida, Hironori, Yoshikazu Masuhiro, Akie Fukushima, Jose Guillermo Martinez Argueta, Noboru Yamaguchi, Susumu Shiota, and Shigemasa Hanazawa. "Identification and Characterization of Novel Isoforms of Human DP-1." Journal of Biological Chemistry 280, no. 26 (April 29, 2005): 24642–48. http://dx.doi.org/10.1074/jbc.m500189200.

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Choubey, Divaker, and Jordan U. Gutterman. "Inhibition of E2F-4/DP-1-stimulated transcription by p202." Oncogene 15, no. 3 (July 1997): 291–301. http://dx.doi.org/10.1038/sj.onc.1201184.

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Fanidi, Abdallah, Eric Vermaas, and Ali R. Fattaey. "INVOLVEMENT OF DP-1 PROTEIN IN E2F-INDUCED CELL DEATH." Biochemical Society Transactions 24, no. 4 (November 1, 1996): 516S. http://dx.doi.org/10.1042/bst024516sc.

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34

Sachan, Richa, Amit Kundu, Prasanta Dey, Ji Yeon Son, Kyeong Seok Kim, Da Eun Lee, Hae Ri Kim, et al. "Dendropanax morbifera Protects against Renal Fibrosis in Streptozotocin-Induced Diabetic Rats." Antioxidants 9, no. 1 (January 19, 2020): 84. http://dx.doi.org/10.3390/antiox9010084.

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The aquatic extract of Dendropanax morbifera (DP) is typically consumed as a beverage in Korea and China and is also used in various traditional medicines. However, the functional role of DP on diabetes-induced renal fibrosis is unclear. Here, the protective effects of DP extract against diabetes-induced renal fibrosis were evaluated. Streptozotocin (STZ, 60 mg/kg) was injected intraperitoneally in rats to induce diabetes. After 5 days, DP extract (25 mg/kg/day) and metformin (50 mg/kg/day) were administered orally to diabetic rats for 28 days. DP administration protected both body and organ weight loss in STZ-treated diabetic rats. Significant improvements in serum blood urea nitrogen (BUN), creatinine, and oxidative stress parameters were observed in diabetic rats by DP administration. DP extract markedly protected diabetic-induced histopathological damages in the kidney and pancreas. A significant reduction was observed in microalbumin, kidney injury molecule-1 (KIM-1), selenium binding protein-1 (SBP1), and pyruvate kinase muscle isozyme M2 (PKM2) levels in the urinary excretion of diabetic rats after the administration of DP extract. The expression of pro-inflammatory cytokines and fibrosis marker levels were significantly reduced in the kidney of diabetic rats. Our results strongly indicate that DP extract exhibits protective activity against diabetes-induced renal fibrosis through ameliorating oxidative stress and inflammation. Therefore, we suggest that DP extract can be used as a preventive agent on the progression of diabetic nephropathy and renal fibrosis.

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Simons, PJ, FG Delemarre, PH Jeucken, and HA Drexhage. "Pre-autoimmune thyroid abnormalities in the biobreeding diabetes-prone (BB-DP) rat: a possible relation with the intrathyroid accumulation of dendritic cells and the initiation of the thyroid autoimmune response." Journal of Endocrinology 157, no. 1 (April 1, 1998): 43–51. http://dx.doi.org/10.1677/joe.0.1570043.

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Thyroid autoimmune reactions start with an accumulation of mainly dendritic cells in the thyroid. There is increasing evidence that, apart from being antigen-presenting cells, they are also able to control the growth and hormone synthesis of neighbouring endocrine cells. The questions thus arise: are dendritic cells accumulating in the pre-autoimmune thyroid in response to an altered proliferative or metabolic activity of thyrocytes, and do cytokines, monocyte chemoattractants, or both, have a role in their accumulation? We have investigated these questions in thyrocytes of the biobreeding diabetes-prone (BB-DP) rat in relation to the start of the intrathyroid accumulation of dendritic cells--that is, at about 9 weeks of age. BB-DP rats and Wistar rats (controls) were studied from 3 to 20 weeks of age. Hyperplastic goitre development was studied by assessing the thyroid weight and by measuring the number of thyrocyte nuclei per 0.01 mm2 thyroid section. In addition, the in situ expression of interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), monocyte-chemotactic protein-1 (MCP-1), and intercellular adhesion molecule-1 (ICAM-1) were studied by immunohistochemistry. The in vitro proliferative capacity of BB-DP and Wistar thyrocytes was measured by tritiated-thymidine ([3H]TdR) and bromodeoxyuridine (BrdU) incorporation into reconstituted, TSH- and non-TSH-stimulated, cultured thyroid follicles. Further in vitro studies consisted of measurement of the production of thyroxine (T4), triiodothyronine (T3), thyroglobulin, IL-6, TNF-alpha and MCP-1 by the thyroid follicles. BB-DP rats developed a small hyperplastic goitre between the ages of 9 and 12 weeks. The in vitro proliferative rate of thyrocytes isolated from hyperplastic BB-DP thyroids was significantly lower than that of Wistar thyrocytes. This phenomenon also occurred in follicles isolated from BB-DP rats before hyperplastic goitre development, which produced significantly less T4, but more T3, than did Wistar follicles of the same age. At the time of and after hyperplastic goitre development, BB-DP follicles exhibited altered metabolic behaviour and produced significantly more T4, but equal amounts of T3 compared with both Wistar follicles of the same age and follicles of younger BB-DP rats (both under basal conditions and TSH-stimulated). In vitro IL-6 production by these BB-DP thyroid follicles was also increased. There was no noteworthy difference in production of thyroglobulin and MCP-1 between BB-DP and Wistar follicles at any age. TNF-alpha was not produced by BB-DP or Wistar thyroid follicles. Immunohistochemistry revealed the expression of IL-6 by both BB-DP and Wistar thyroid follicle cells at all times of sampling. MCP-1 and TNF-alpha were expressed only when infiltrates were present in BB-DP thyroids (restricted to leucocytes, ages > 18 weeks). Modest ICAM-1 expression was restricted to large blood vessels in both BB-DP and Wistar thyroids; in the case of infiltrates (BB-DP rat) alone, high ICAM-1 expression was found on blood vessels and leucocytes in these infiltrations. At the time of intrathyroidal dendritic cells accumulation, BB-DP rats develop a small hyperplastic goitre. At that time there is also in vitro evidence for a shift to a higher production of thyroxine and IL-6 from thyrocyte follicles. The in vitro proliferation rate of BB-DP thyrocytes is, however, abnormally low (both in the pre- and hyperplastic period). Similar pre-autoimmune thyroid growth abnormalities have been described in another animal model of thyroid autoimmune disease, the obese strain chicken.

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Patel, M., T. Hayes, and G. Coast. "Evidence for the hormonal function of a CRF-related diuretic peptide (Locusta-DP) in Locusta migratoria." Journal of Experimental Biology 198, no. 3 (March 1, 1995): 793–804. http://dx.doi.org/10.1242/jeb.198.3.793.

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Locusta-DP is a corticotropin-releasing factor (CRF)-related diuretic peptide isolated from the migratory locust Locusta migratoria. At nanomolar concentrations, synthetic Locusta-DP stimulated fluid secretion and cyclic AMP production by Malpighian tubules isolated in vitro and increased the rate of amaranth clearance in starved locusts to levels comparable with those observed during post-feeding diuresis. The peptide also caused a marked (approximately 10 %), but short-lived, reduction in the haemolymph volume of starved locusts. A polyclonal antiserum raised against Locusta-DP(29-46) was shown to block peptidergic signal transfer in vitro and in vivo. Pre-treatment of Locusta-DP (5 nmol l-1) with antiserum diluted 1:100 resulted in a rapid reduction in the free peptide concentration to less than 1 nmol l-1, the threshold for a measurable effect on cyclic AMP production by isolated tubules. In intact insects, passive immunization with Locusta-DP antiserum blocked increases in the rate of amaranth clearance in response to exogenous diuretic peptide or in response to feeding. The latter was due specifically to the binding of Locusta-DP, because when the relevant antibodies were preadsorbed with Locusta-DP(29-46), the antiserum had no effect on amaranth clearance by recently fed insects. This provides unequivocal evidence of a hormonal function for Locusta-DP in the control of primary urine production.

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Takayama, Rina, Moe Ishizawa, Miyuki Yamada, Yutaka Inoue, and Ikuo Kanamoto. "Characterization of Soluplus/ASC-DP Nanoparticles Encapsulated with Minoxidil for Skin Targeting." ChemEngineering 5, no. 3 (August 2, 2021): 44. http://dx.doi.org/10.3390/chemengineering5030044.

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Soluplus (Sol) is an amphiphilic graft copolymer capable of forming self-assembled micelles and L-ascorbyl 2,6-dipalmitate (ASC-DP) aggregates spontaneously to form micelles. Micelles are used as drug carriers and can nanoparticulate drugs that are poorly soluble in water, such as minoxidil. The study aimed to prepare minoxidil-encapsulated nanoparticles using Sol/ASC-DP and evaluate their potential for targeted skin application. Sol/ASC-DP nanoparticles or Sol/ASC-DP with minoxidil were prepared using the hydration method, and physical evaluations were carried out, including assessments of particle size and zeta potential. Particle structure was evaluated by transmission electron microscopy (TEM) and 1H-nuclear magnetic resonance spectra to assess particle stability and perform functional evaluations in skin penetration tests. TEM images showed spherical micelle-like particles of approximately 100 nm for Sol/ASC-DP at a 9:1 ratio and of approximately 80 nm for Sol/ASC-DP with incorporated minoxidil at a 9:1:0.5 ratio. Changes were also observed in the solid state, suggesting a hydrophobic interaction between Sol and ASC-DP. In addition, evaporated microparticles (Sol/ASC-DP/minoxidil = 9/1/0.5) improved the skin permeability of minoxidil. These results suggest that Sol/ASC-DP nanoparticles form a stable new nanoparticle due to hydrophobic interactions, which would improve the skin permeability of minoxidil.

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Zope, Murlidhar V., Rahul M. Patel, Ashwinikumari Patel, and Samir G. Patel. "DEVELOPMENT AND VALIDATION OF A STABILITY INDICATING RP-HPLC METHOD FOR THE DETERMINATION OF POTENTIAL DEGRADATION PRODUCTS OF DIFLUPREDNATE IN OPHTHALMIC EMULSION." International Journal of Pharmacy and Pharmaceutical Sciences 10, no. 9 (September 1, 2018): 79. http://dx.doi.org/10.22159/ijpps.2018v10i9.26342.

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Objective: The objective of the current study was to develop and validate a simple, robust, precise and accurate RP-HPLC (reverse phase-high performance liquid chromatography) method for the quantitative determination of potential degradation products of Difluprednate (DIFL) in the ophthalmic emulsion.Methods: Chromatographic separation was achieved on the YMC pack ODS-AQ (150× 4.6) mm, 3μm column with a mobile phase containing a gradient mixture of mobile phase A (0.02M Ammonium formate buffer pH 4.5 adjusted with formic acid) and Acetonitrile as mobile phase B, at flow rate of 1.5 ml/min and with UV detection at 240 nm.Results: The peak retention time of DIFL was found at about 17.2 min, the RRT of degradation product-1 (DP-1), degradation product-2 (DP-2), and degradation product-3 (DP-3), were found to be about 0.49, 0.65 and 0.79 respectively (calculated with respect to Difluprednate). Stress testing was performed in accordance with an ICH (international council for harmonisation) guideline Q1A (R2) [1]. The method was validated as per ICH guideline Q2 (R1)[2]. The calibration curve was found to be linear in the concentration range of 0.1 to 0.75 µg/ml for Difluprednate, DP-1, DP-2 and DP-3. The LOD (Limit of detection) was found to be 0.1µg/ml and LOQ (Limit of quantification) of 0.15µg/ml for Difluprednate, DP-1, DP-2 and DP-3 respectively. The recovery from LOQ to 150% was within 90-110%. The forced degradation data confirms the stability indicating the nature of the method.Conclusion: A simple, robust, precise and accurate RP-HPLC method for the quantitative determination of potential degradation products of Difluprednate in the ophthalmic emulsion was developed and validated.

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Guduru, Santhosh, V. V. S. R. N. Anji Karun Mutha, B. Vijayabhaskar, Muralidharan Kaliyaperumal, Raghu Babu Korupolu, Kishore Babu Bonige, and Chidananda Swamy Rumalla. "Isolation and Structural Characterization of Degradation Products of Aceclofenac by HPLC, HRMS and 2D NMR." Asian Journal of Chemistry 31, no. 4 (February 27, 2019): 851–54. http://dx.doi.org/10.14233/ajchem.2019.21798.

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The stability of aceclofenac under stress conditions was assessed to identify the degradation products. So, it was subjected to stress conditions like acid, base and oxidation, according to ICH guideline Q1A (R2). One degradation product formed when the drug was subjected to acid stress. Three degradation products were formed during the basic stress condition. The drug substance was found to be stable to oxidative stress. The degradants formed during the stress were separated on a C-18 column using gradient preparative HPLC elution. The only product (DP-2) formed during the acid stress and this one is same as of one of the three degradation products (DP-1, DP-2, DP-3) were formed during base stress. 1D and 2D NMR spectra and mass spectral analysis supported the proposed structures for the products. The products DP-2 and DP-3 have been reported earlier but this is the first report of product DP-1 as a degradation product of aceclofenac.

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40

Tavares, Wendy, Daniel J. Drucker, and Patricia L. Brubaker. "Enzymatic- and renal-dependent catabolism of the intestinotropic hormone glucagon-like peptide-2 in rats." American Journal of Physiology-Endocrinology and Metabolism 278, no. 1 (January 1, 2000): E134—E139. http://dx.doi.org/10.1152/ajpendo.2000.278.1.e134.

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The intestinotropic hormone glucagon-like peptide (GLP)-2-(1—33) is cleaved in vitro to GLP-2-(3—33) by dipeptidyl peptidase IV (DP IV). To determine the importance of DP IV versus renal clearance in the regulation of circulating GLP-2-(1—33) levels in vivo, GLP-2-(1—33) or the DP IV-resistant analog [Gly2]GLP-2 was injected in normal or DP IV-negative rats and assayed by HPLC and RIA. Normal rats showed a steady degradation of GLP-2-(1—33) to GLP-2-(3—33) over time, whereas little or no conversion was detected for GLP-2-(1—33) in DP IV-negative rats and for [Gly2]GLP-2 in normal rats. To determine the role of the kidney in clearance of GLP-2-(1—33) from the circulation, normal rats were bilaterally nephrectomized, and plasma immunoreactive GLP-2 levels were measured. The slope of the disappearance curves for both GLP-2-(1—33) and [Gly2]GLP-2 were significantly reduced in nephrectomized compared with nonnephrectomized rats ( P < 0.01). In contrast to both GLP-2-(1—33) and [Gly2]GLP-2, GLP-2-(3—33) did not stimulate intestinal growth in a murine assay in vivo. Thus the intestinotropic actions of GLP-2-(1—33) are determined both by the actions of DP IV and by the kidney in vivo in the rat.

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Álvarez, Adriana, Andrea Kozak, Lucas Costa, Guillermo Alzueta, Juan Bauchi, Claudia De Boni, Guillermo Dieuzeide, et al. "Evaluación de la funcionalidad del eje hipotálamo-hipófiso-adrenal a través del test de respuesta del cortisol al despertar en pacientes con diabetes mellitus tipo 1 con y sin depresión: Estudio Multicéntrico Argentino (EMA-1)." Revista de la Sociedad Argentina de Diabetes 54, no. 3 (December 14, 2020): 132. http://dx.doi.org/10.47196/diab.v54i3.454.

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Introducción: la depresión (DP) tiene una alta prevalencia en pacientes con diabetes mellitus tipo 1 (DM1) y se asocia a repercusiones clínicas negativas como mayor morbimortalidad cardiovascular y complicaciones crónicas. Existen pocos estudios publicados sobre la funcionalidad del eje hipotálamo-hipófiso-adrenal (H-H-A) en DM1 con DP, y la relación entre la DP y el test de respuesta del cortisol al despertar (RCD) con el control glucémico (CG).Objetivos: analizar la funcionalidad del eje H-H-A a través de la evaluación del RCD en pacientes con DM1 (PD1) con y sin DP. Como objetivos secundarios, conocer la prevalencia de DP en PD1 y ver si existe relación entre el RCD y CG y entre DP y CG.Materiales y métodos: estudio observacional, prospectivo, de corte transversal, multicéntrico, nacional. Se incluyeron PD1 mayores de 18 años; se utilizó cuestionario Patient Health Questionnaire-9 (PHQ-9) para diagnóstico de DP. Se tomaron muestras de cortisol salival al despertar y a los 30 minutos (RCD), y se consideró RCD bloqueado si el valor de cortisol de los 30 minutos no aumentaba más del 50% del basal. Además se tomaron muestras de sangre en ayunas para medir glucemia, fructosamina y HbA1c.

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Lee, J. S. "Distension pressure on subserosal and mesenteric lymph pressures of rat jejunum." American Journal of Physiology-Gastrointestinal and Liver Physiology 251, no. 5 (November 1, 1986): G611—G614. http://dx.doi.org/10.1152/ajpgi.1986.251.5.g611.

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Lymph pressure (Pl) in the subserosal lymphatics and mesenteric lymphatics was determined in the jejunum at various intraluminal distension pressures (DP). Pl in the subserosal lymphatics was approximately equal to DP, in the range of 3–100 mmHg, whether the intestine was in the basal state or during water absorption. At a DP of 0 mmHg, Pl was 1.5 +/- 0.1 mmHg. When DP was 3, 10, 20, 40, 70, or 100 mmHg, Pl was 2.9 +/- 0.2, 11 +/- 1, 23 +/- 1, 43 +/- 1, 71 +/- 2, or 102 +/- 2 mmHg, respectively. From these findings and other considerations it is inferred that Pl in the subserosal lymphatics could be similar to the tissue fluid pressure, which is apparently determined by DP due to compression of the intestinal wall. On the other hand, Pl in the mesenteric lymphatics was not affected by DP at all. When DP was in the range of 0–70 mmHg with free flow of lymph, mean Pl was 6-8 mmHg, and it was 23–28 mmHg during lymphatic obstruction. During pressure measurement, rhythmical contractions of these lymphatics occurred, which may be mainly responsible for the increase of Pl and propulsion of lymph as well.

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43

Li, Jin Bao, Mei Yun Zhang, Hui Juan Xiu, and Xin Ping Li. "Rheological Characteristics on Solution of NMMO/Cellulose with Different Degree of Polymerization and its Combination." Advanced Materials Research 568 (September 2012): 396–99. http://dx.doi.org/10.4028/www.scientific.net/amr.568.396.

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Impacts of temperature, shear rate, cellulose concentration and DP proportion on rheological behavior of cellulose/NMMO•H2O solution were investigated in this paper; especially put forward a method of mixing different DP cellulose at different proportion to discuss more accurately effect of DP. The results shown that the flow activation energy of 4% cellulose/NMMO•H2O was 24.45kJ/mol, and the temperature 85～115°Cwas suited for its processing. All kinds of cellulose solution with different DP were the pseudoplastic fluid, and had shear thinning characteristic, especially high DP. The cellulose concentration was higher, apparent viscosity of its solution was bigger, but their relationship was not linear. Under the same cellulose concentration, the solution viscosity increased generally in proportion to DP rising, but the solution with proportion 1:1 was one exception, and its viscosity is relatively high.

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44

Baheti, Gautam, Jennifer J. Kiser, Peter L. Havens, and Courtney V. Fletcher. "Plasma and Intracellular Population Pharmacokinetic Analysis of Tenofovir in HIV-1-Infected Patients." Antimicrobial Agents and Chemotherapy 55, no. 11 (September 6, 2011): 5294–99. http://dx.doi.org/10.1128/aac.05317-11.

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ABSTRACTThe relationships among the dose of tenofovir disoproxil fumarate (TDF), tenofovir (TFV) plasma concentrations, and intracellular TFV diphosphate (TFV-DP) concentrations are poorly understood. Our objective was to characterize TFV and TFV-DP relationships. Data were pooled from two studies in HIV-infected persons (n= 55) on stable antiretroviral therapy. TFV and TFV-DP were measured with validated liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods. Nonlinear mixed effects modeling (NONMEM 7) was used to develop the population model and explore the influence of covariates on TFV. A sequential analysis approach was utilized. A two-compartment model with first-order absorption best described TFV PK (FOCEI). An indirect stimulation of response model best described TFV-DP, where formation of TFV-DP was driven by plasma TFV concentration. Final plasma population estimates were as follows: absorption rate constant, 1.03 h−1; apparent clearance (CL/F), 42 liters/h (33.5% interindividual variability [IIV]); intercompartment clearance, 181 liters/h; apparent central distribution volume (Vc/F), 273 liters (64.8% IIV); and apparent peripheral distribution volume (Vp/F), 440 liters (46.5% IIV). Creatinine clearance was the most significant covariate on CL/F and Vc/F. The correlation between CL/F and Vc/F was 0.553. The indirect response model for TFV-DP resulted in estimates of the maximal intracellular concentration (Emax), the TFV concentration producing 50% ofEmax(EC50), and the intracellular elimination rate constant (kout) of 300 fmol/106cells (82% IIV), 100 ng/ml (106% IIV), and 0.008 h−1, respectively. The estimatedkoutgave an 87-h TFV-DP half-life. A predictive check assessment indicated satisfactory model performance. This model links formation of TFV-DP with plasma TFV concentrations and should facilitate more informed investigations of TFV clinical pharmacology.

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Ma, Junnan, Renny J. van Hoeij, Rupert M. Bruckmaier, Akke Kok, Theo J. G. M. Lam, Bas Kemp, and Ariette T. M. van Knegsel. "Consequences of Transition Treatments on Fertility and Associated Metabolic Status for Dairy Cows in Early Lactation." Animals 10, no. 6 (June 25, 2020): 1100. http://dx.doi.org/10.3390/ani10061100.

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This study aimed to (1) investigate effects of reducing postpartum dietary energy level for cows after a 0-d dry period (DP) on resumption of ovarian cyclicity and reproductive performance, (2) relate days open with other reproductive measures, and (3) relate onset of luteal activity (OLA) and days open with metabolic status in early lactation. Holstein-Friesian dairy cows were randomly assigned to 1 of 3 transition treatments: no DP and low postpartum dietary energy level from 22 days in milk( DIM )onwards (0-d DP (LOW)) (n = 42), no DP and standard postpartum dietary energy level (0-d DP (STD)) (n = 43), and a short DP and standard postpartum dietary energy level (30-d DP (STD)) (n = 43). Milk progesterone concentration was determined three times per week until 100 DIM. Plasma metabolite and hormone concentrations were measured weekly until week 7 postpartum. Reducing postpartum dietary energy level in older cows (parity ≥ 3) after no DP and 22 DIM did not affect milk production but prevented a positive energy balance and shortened the interval from calving to OLA. In addition, services per pregnancy and days open were reduced in cows of parity ≥ 3 on 0-d DP (LOW), compared with cows of parity ≥ 3 with 0-d DP (STD), but not in cows of parity 2.

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Bernardini, R., G. Mistrello, E. Novembre, D. Roncarolo, S. Zanotta, E. Lombardi, A. Cianferoni, N. Pucci, M. De Martino, and A. Vierucci. "Cross-Reactivity between IgE-Binding Proteins from Anisakis Simplex and Dermatophagoides Pteronyssinus." International Journal of Immunopathology and Pharmacology 18, no. 4 (October 2005): 671–75. http://dx.doi.org/10.1177/039463200501800408.

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An association was found between Anisakis simplex (As) and Dermatophagoides pteronyssinus (Dp) sensitization. One recent study shows a cross-reactivity between As and Dp and tropomyosin (tr) is suspected as being one of the proteins responsible of this cross-reaction. The aim of our study was: 1) to confirm the cross-reactivity between Dp and As; 2) to determine the importance of tr in this cross reaction. SDS-PAGE analysis of Dp and As (metabolic and somatic) extracts was carried out. Then an IgE immunoblotting test using serum from a patient who had specific IgE only to Dp and As and immunoblotting inhibition experiments using Dp extract and tr as inhibitors were performed. We found that patient's serum reacted: 1) against larval As antigens with a molecular weight (mw) of 25 kilodalton (kD) and a mw > 100 kD, 2) against various metabolic As antigens with a mw > 100 kD, a mw ranging approximately from 35 to 50 kD, and a mw around 20 kD, and 3) against Dp proteins with mw between 35 and 55 kD. Preincubation of patient's serum with Dp extract caused the disappearance of reactivity against antigens with a mw > 100 kD in both larval and metabolic As extracts and against proteins with mw ranging approximately from 35 to 50 kD in the metabolic As extract. Preincubation of patient's serum with As extract caused the disappearance of reactivity against antigens with mw between 35 and 55 kD in the Dp extract. Pre-incubation of patient's serum with tr did not induce any change in the immunoblotting profile. The results show that 1) cross-reactive components between Dp and As are some proteins with a mw ranging approximately from 35 to 50 kD and with a mw > 100 kD, and 2) tr is not involved in cross-reactivity between As and Dp.

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47

Birdsey, T. J., S. M. Husain, H. O. Garland, and C. P. Sibley. "The effect of diabetes mellitus on urinary calcium excretion in pregnant rats and their offspring." Journal of Endocrinology 145, no. 1 (April 1995): 11–18. http://dx.doi.org/10.1677/joe.0.1450011.

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Abstract The effect of maternal diabetes mellitus on renal calcium excretion in pregnant rats and their offspring has been examined in order to ascertain the role of the kidney in the disturbed calcium homeostasis of infants born to diabetic mothers. Diabetic pregnant (DP) rats exhibited severe hypercalciuria which greatly exceeded the urinary calcium losses (UCaV) in non-diabetic pregnant (CP) or non-pregnant diabetic (D) rats. Means ± s.e.m. for UCaV at day 21 (mmol/24 h) were: DP=1·12± 0·09 (n=7); CP=0·06±0·01 (n=7); D=0·63±0·06 (n=7) (P<0·001 DP vs CP and DP vs D). The profile for urinary calcium excretion in the three groups was different from that of other measured ions. The degree of natriuresis, for example, was comparable in DP and D rats at all stages studied. Although magnesium output was significantly greater in DP than D rats on days 14 and 21, this appeared to result from an additive effect of the magnesiuresis seen when pregnancy and diabetes were studied separately. The marked renal calcium wasting of diabetic pregnancy will have implications for overall calcium balance in the mother. For example, an enhanced intestinal calcium absorption was seen in DP rats in the second half of gestation. Means ± s.e.m. for day 21 (mmol/24 h) were: DP=3·8±0·8 (n=7); CP=1·4±0·3 (n=7); D=1·6±0·3 (n=7) (P<0·05 DP vs CP and DP vs D). The hypercalciuria may also contribute to the disturbed calcium homeostasis of the neonate if it reduces the amount of calcium available for transfer to the fetus. In contrast to their mothers, the offspring of DP rats did not show a raised UCaV compared with CP pups. Means ± s.e.m. at day 1 postpartum (nmol/2 h per pup) were: DP=47·2±15·7 (n=4 litters); CP=72·2±14·1 (n=7 litters) (not significant). Changes in neonatal renal function are therefore unlikely to contribute to their disturbed calcium balance. In fact, their slightly reduced urinary calcium output may be an attempt to compensate for their lowered total body calcium as reported elsewhere. Journal of Endocrinology (1995) 145, 11–18

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Kim, Chong S., and Shu-Chieh Hu. "Total respiratory tract deposition of fine micrometer-sized particles in healthy adults: empirical equations for sex and breathing pattern." Journal of Applied Physiology 101, no. 2 (August 2006): 401–12. http://dx.doi.org/10.1152/japplphysiol.00026.2006.

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Accurate dose estimation under various inhalation conditions is important for assessing both the potential health effects of pollutant particles and the therapeutic efficacy of medicinal aerosols. We measured total deposition fraction (TDF) of monodisperse micrometer-sized particles [particle diameter (Dp) = 1, 3, and 5 μm in diameter] in healthy adults (8 men and 7 women) in a wide range of breathing patterns; tidal volumes (Vt) of 350–1500 ml and respiratory flow rates (Q̇) of 175–1,000 ml/s. The subject inhaled test aerosols for 10–20 breaths with each of the prescribed breathing patterns, and TDF was obtained by monitoring inhaled and exhaled aerosols breath by breath by a laser aerosol photometer. Results show that TDF varied from 0.12–0.25, 0.26–0.68, and 0.45–0.83 for Dp = 1, 3, and 5 μm, respectively, depending on the breathing pattern used. TDF was comparable between men and women for Dp = 1 μm but was greater in women than men for Dp = 3 and 5 μm for all breathing patterns used ( P < 0.05). TDF increased with an increase in Vt regardless of Dp and Q̇ used. At a fixed Vt TDF decreased with an increase in Q̇ for Dp = 1 and 3 μm but did not show any significant changes for Dp = 5 μm. The varying TDF values, however, could be consolidated by a single composite parameter (ω) consisting of Dp, Vt, and Q̇. The results indicate that unifying empirical formulas provide a convenient means of assessing deposition dose of particles under varying inhalation conditions.

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Ferreira, Tereza Cristina dos Reis, Lilianne do Socorro Guimarães Freitas, Amanda Santos Ruffeil, Amanda Jordana Silva Souza, Paulo Vitor de Souza Sassim, Júlio César Veiga Pena, Paula Thayna Soares Lima, and Jaqueline Pinheiro da Silva. "OS EFEITOS DO MÉTODO PILATES NA APTIDÃO CARDIORRESPIRATÓRIA EM TRABALHADORAS DA INDÚSTRIA." Centro de Pesquisas Avançadas em Qualidade de Vida, v12n3 (January 1, 2021): 1–10. http://dx.doi.org/10.36692/v12n3-47.

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Introdução: O presente trabalho propõe a utilização do método pilates como melhora da aptidão cardiorrespiratória em trabalhadoras da indústria. Objetivos: Verificar os efeitos que o método Pilates exerce na aptidão cardiorrespiratória em trabalhadoras da indústria antes e após intervenção. Métodos: Foram avaliadas 10 trabalhadoras da indústria com idade entre 18 e 59 com média de 46,3 anos. Foram avaliados dados antropométricos de massa corporal e estatura (WELNY 0-150KG/1 -2,20M), Índice de Massa Corporal (IMC) e perimetria. Para mensurar o VO2máx foi efetuado o teste de banco através do protocolo de Cirilo onde a frequência cardíaca e pressão arterial foram aferidas em repouso e pós-esforço, o resultado foi aplicado em uma equação específica a fim de averiguar o nível de capacidade aeróbica (MULHER: VO2 máx [ml(kg.min)-1] = 65.81 - [0.1847 x FC(bpm)]19). Após as 24 sessões os dados foram catalogados e arquivados em base de dados em planilha construída no programa SPSS 20. De acordo com a natureza das variáveis foi efetuada uma análise descritiva onde os percentuais obtidos foram expressos na forma de média e desvio padrão (DP) com o intuito de verificar a significância estatística. Resultados: Os resultados obtidos quanto à massa corporal e estatura obteve-se média de (62,67kg e DP± 9,46kg; 1,56m e DP ± 0,05m) na avaliação e (62,07kg e DP ± 8,87kg; 1,57m e DP ± 0,05m) na reavaliação. Quanto ao VO2máx obteve-se média de (36,75 mL.Kg-1.min-1 e DP ± 3,84 mL.Kg-1.min-1) na avaliação e de (38,08 mL.Kg-1.min-1 e DP ± 3,84 mL.Kg-1.min-1) na reavaliação. Conclusões: Verificou-se que a aplicação do método Pilates influencia de forma positiva na aptidão cardiorrespiratória, diminuindo o risco de doenças ostemusculares e ocupacionais e evitando um possível afastamento do trabalho.

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Li, Jin Bao, Mei Yun Zhang, Hui Juan Xiu, and Xin Ping Li. "Impact of Degree of Polymerization Combination on Structure and Properties of Cellulose Membrane." Advanced Materials Research 568 (September 2012): 275–78. http://dx.doi.org/10.4028/www.scientific.net/amr.568.275.

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Influence of degree of polymerization (DP) on the microstructure, crystallinity and strength properties of cellulose membrane were investigated in this paper; especially put forward a method of mixing different DP cellulose at different proportion to discuss more accurately effect of DP. The results show that the membrane at the proportion of 3:1 possesses the loosest structure, followed by 1:3 and 1:1 in turn. Cellulose’s crystalline structure had changed during NMMO process, and transformed from cellulose Ⅰ in cellulose pulps to cellulose Ⅱ in regenerated cellulose membrane, but could not form cellulose Ⅰ again. In addition, it can be found that crystallinity decrease remarkably, and the lattice size also reduces to a certain extent. Cellulose membrane at the proportion 1:1 was of the highest crystallinity and tensile strength, but its elongation keeps a continuous decline as mean DP decreasing.

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Journal articles on the topic 'DP-1'

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