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Sample records for alpha-induced luteal regression

  1. Apoptosis during spontaneous and prostaglandin F(2alpha)-induced luteal regression in the buffalo cow (Bubalus bubalis): involvement of mitogen-activated protein kinases.

    PubMed

    Yadav, Vijay K; Sudhagar, Ranga R; Medhamurthy, R

    2002-09-01

    The present study was conducted to evaluate whether the corpus luteum (CL) of the water buffalo (Bubalus bubalis) cow undergoes luteal regression by the process of apoptosis and to examine the involvement of mitogen-activated protein (MAP) kinases during prostaglandin (PG) F(2alpha)-induced luteolysis. Sections of CL from late in the estrous cycle, i.e., during spontaneous luteolysis, stained for 4',6'-diamidino-2-phenylindole revealed increased numbers of condensed nuclei, indicating cell death by apoptosis, which was confirmed further by the occurrence of pronounced oligonucleosome formation. For morphological and biochemical characterization during PGF(2alpha)-induced apoptosis, CL were collected at 0, 4, 12, and 18 h after injection of 750 micro g of Tiaprost, a synthetic analogue of PGF(2alpha), to midestrous buffalo cows. Serum progesterone concentrations fell within 4 h and decreased (P < 0.05) maximally by 18 h. Concomitant decreases (P < 0.05) in the levels of steroidogenic acute regulatory mRNA and protein were observed in CL during 12-18 h, with the more profound effect on mRNA levels. Quantitative analysis of the genomic DNA showed a >5-fold increase (P < 0.05) in the low molecular weight DNA fragments by 18 h postinjection. Immunoblot analysis of CL tissue lysates showed increased (P < 0.05) levels of phospho-Jun N-terminal kinase (JNK) 1 (4- to 14-fold during 4-18 h) and phospho-p38 (2- to 4-fold at 18 h). Immunohistochemical evaluation of CL sections revealed an increased nuclear localization of phospho-JNK after treatment. These findings demonstrate that the CL of the buffalo cow undergoes cell death by the process of apoptosis both during spontaneous and PGF(2alpha)-induced luteolysis and that MAP kinases are involved during PGF(2alpha)-mediated apoptosis in the CL.

  2. Can luteal regression be reversed?

    PubMed Central

    Telleria, Carlos M

    2006-01-01

    The corpus luteum is an endocrine gland whose limited lifespan is hormonally programmed. This debate article summarizes findings of our research group that challenge the principle that the end of function of the corpus luteum or luteal regression, once triggered, cannot be reversed. Overturning luteal regression by pharmacological manipulations may be of critical significance in designing strategies to improve fertility efficacy. PMID:17074090

  3. Prostaglandin F2 alpha-induced calcium transient in ovine large luteal cells: II. Modulation of the transient and resting cytosolic free calcium alters progesterone secretion.

    PubMed

    Wegner, J A; Martinez-Zaguilan, R; Gillies, R J; Hoyer, P B

    1991-02-01

    A previous study demonstrated that prostaglandin F2 alpha (PGF2 alpha) stimulates a transient increase in cytosolic free Ca2+ levels [( Ca2+]i) in ovine large luteal cells. In the present study, the magnitude of the PGF2 alpha (0.5 microM)-induced calcium transient in Hanks' medium (87 +/- 2 nM increase above resting levels) was reduced (P less than 0.05) but not completely eliminated in fura-2 loaded large luteal cells incubated in Ca2(+)-free or phosphate- and carbonate-free medium (10 +/- 1 nM, 32 +/- 6 nM, above resting levels; respectively). Preincubation for 2 min with 1 mM LaCl3 (calcium antagonist) eliminated the PGF2 alpha-induced calcium transient. The inhibitory effect of PGF2 alpha on secretion of progesterone was reduced in Ca2(+)-free medium or medium plus LaCl3. Resting [Ca2+]i levels and basal secretion of progesterone were both reduced (P less than 0.05) in large cells incubated in Ca2(+)-free medium (27 +/- 4 nM; 70 +/- 6% control, respectively) or with 5 microM 5,5'-dimethyl bis-(O-aminophenoxy)ethane-N,N,N'N'-tetraacetic acid (40 +/- 2 nM; 49 +/- 1% control; respectively). In addition, secretion of progesterone was inhibited (P less than 0.05) by conditions that increased (P less than 0.05) [Ca2+]i; that is LaCl3 ([Ca2+]i, 120 +/- 17 nM; progesterone, 82 +/- 8% control) and PGF2 alpha ([Ca2+]i, 102 +/- 10 nM; progesterone, 82 +/- 3% control). In small luteal cells, resting [Ca2+]i levels and secretion of progesterone were reduced by incubation in Ca2(+)-free Hanks ([Ca2+]i, 28 +/- 2 nM; progesterone, 71 +/- 6% control), however, neither LaCl3 nor PGF2 alpha increased [Ca2+]i levels or inhibited secretion of progesterone. The findings presented here provide evidence that extracellular as well as intracellular calcium contribute to the PGF2 alpha-induced [Ca2+]i transient in large cells. Furthermore, whereas an adequate level of [Ca2+]i is required to support progesterone production in both small and large cells, optimal progesterone production in

  4. Luteal regression vs. prepartum luteolysis: regulatory mechanisms governing canine corpus luteum function.

    PubMed

    Kowalewski, Mariusz P

    2014-04-01

    Canine reproductive physiology exhibits several unusual features. Among the most interesting of these are the lack of an acute luteolytic mechanism, coinciding with the apparent luteal independency of a uterine luteolysin in absence of pregnancy, contrasting with the acute prepartum luteolysis observed in pregnant animals. These features indicate the existence of mechanisms different from those in other species for regulating the extended luteal regression observed in non-pregnant dogs, and the actively regulated termination of luteal function observed prepartum as a prerequisite for parturition. Nevertheless, the supply of progesterone (P4) depends on corpora lutea (CL) as its primary source in both conditions, resulting in P4 levels that are similar in pregnant and non-pregnant bitches during almost the entire luteal life span prior to the prepartum luteolysis. Consequently, the duration of the prolonged luteal phase in non-pregnant bitches frequently exceeds that of pregnant ones, which is a peculiarity when compared with other domestic animal species. Both LH and prolactin (PRL) are endocrine luteotrophic factors in the dog, the latter being the predominant one. In spite of increased availability of these hormones, luteal regression/luteolysis still takes place. Recently, possible mechanisms regulating the expression and function of PRL receptor have been implicated in the local, i.e., intraluteal regulation of PRL bioavailability and thus its steroidogenic potential. Similar mechanisms may relate to the luteal LH receptor. Most recently, evidence has been provided for an autocrine/paracrine role of prostaglandin E2 (PGE2) as a luteotrophic factor in the canine CL acting at the level of steroidogenic acute regulatory (STAR)-protein mediated supply of steroidogenic substrate, without having a significant impact on the enzymatic activity of the respective steroidogenic enzymes, 3β-hydroxysteroid-dehydrogenase (3βHSD, HSD3B2) and cytochrome P450 side

  5. Androstenedione interferes in luteal regression by inhibiting apoptosis and stimulating progesterone production.

    PubMed

    Goyeneche, Alicia A; Calvo, Virginia; Gibori, Geula; Telleria, Carlos M

    2002-05-01

    Androgens, in concert with lactogenic hormones, contribute to the maintenance of function of the corpus luteum (CL) in pregnant rats. Whereas some of the androgenic actions in the CL are clearly mediated by intracrine conversion to estrogen, pure androgenic effects are also implicated in the regulation of this transient endocrine gland. In this report, we have established, to our knowledge for the first time, the expression of androgen receptor (AR) mRNA and protein throughout gestation in the rat CL. We have found that the AR remains expressed in the CL of gestation on Day 4 postpartum and becomes expressed in the newly formed CL after postpartum ovulation. An AR immunoreactive protein was identified in the CL of pregnancy as well as in prostate and epididymis, which were used as positive controls. The luteal AR protein had mainly nuclear localization, yet some diffuse cytoplasmic staining was also observed. Moreover, we have established that androstenedione, the main circulating androgen in pregnant rats, significantly reduces the decline in luteal weight observed during postpartum structural regression. This effect was correlated with a decrease in the number of cells undergoing apoptosis and with enhanced levels of circulating progesterone. In addition, in vivo administration of androstenedione delayed the occurrence of DNA fragmentation in postpartum CL incubated in serum-free conditions. Finally, we have shown that the interference with apoptosis in vitro elicited by androstenedione is accompanied by an increased capacity of the CL to secrete progesterone. In summary, the results of this study have established that the rat CL expresses AR throughout pregnancy and after parturition, and they have defined a potential role for androstenedione in opposing postpartum luteal regression through inhibition of apoptosis and stimulation of progesterone production.

  6. Regulation of lipid peroxidation by nitric oxide and PGF2alpha during luteal regression in rats.

    PubMed

    Motta, A B; Estevez, A; Franchi, A; Perez-Martinez, S; Farina, M; Ribeiro, M L; Lasserre, A; Gimeno, M F

    2001-04-01

    Corpus luteum regression is related to an increased generation of reactive oxygen species. Although several studies indicate that PGF(2alpha) is involved in regression of the corpus luteum in mammalian species through an increase in reactive oxygen species, the exact mechanism remains unknown. In the present study, the relationship between nitric oxide and PGF(2alpha) in regulation of lipid peroxidation was studied. Ovarian tissue from pseudopregnant rats at mid- (day 5) or late phase or at the time of regression (day 9 of pseudopregnancy) of corpus luteum development was used. Thiobarbituric acid reactants, used as a lipid peroxidation index, were higher on day 9 of pseudopregnancy than on day 5. In contrast, glutathione content (an antioxidant metabolite) was lower on day 9 than on day 5 of pseudopregnancy. These results indicate that there was an enhanced oxidative status in ovarian tissue during luteolysis. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME: 600 micromol l(-1)), a competitive nitric oxide synthase (NOS) inhibitor, led to a decrease in basal thiobarbituric acid reactant content in ovarian tissue from rats on day 9 of pseudopregnancy only, indicating that during regression of the corpus luteum, NO could act as intermediary in ovarian lipid peroxidation. Administration of a luteolytic dose (3 microg kg(-1) body weight i.p.) of a synthetic PGF(2alpha) increased thiobarbituric acid reactant content in ovaries from rats on day 9 of pseudopregnancy. As this effect was reversed partially by L-NAME, it is proposed that during regression of corpora lutea, PGF(2alpha) and NO are involved in regulation of lipid peroxidation. As this effect was only reversed partially, it is possible that there is another mechanism involving PGF(2alpha) (but not the NO-NOS pathway) in regulation of ovarian lipid peroxidation. Furthermore, the administration of PGF(2alpha) enhanced ovarian NOS activity, whereas cyclooxygenase inhibition (by indomethacin

  7. Control of human luteal steroidogenesis.

    PubMed

    Devoto, Luigi; Kohen, Paulina; Vega, Margarita; Castro, Olga; González, Rubén René; Retamales, Iván; Carvallo, Pilar; Christenson, Lane K; Strauss, Jerome F

    2002-01-25

    The human corpus luteum (CL) undergoes a dynamic cycle of differentiation, steroid hormone production and regression during the course of non-fertile cycles. In humans and other primates, luteal steroidogenesis is absolutely dependent on pituitary-derived LH. However, changes in LH and LH receptor expression do not explain the marked decline in progesterone production at the end of the luteal phase. Changes in the level of the steroidogenic acute regulatory protein (StAR), a gene whose expression is controlled by LH most likely account for the cyclic pattern of progesterone production. During the mid-to-late luteal phase of a fertile cycle, chorionic gonadotropin (hCG) rescues the CL, overcoming the actions of the factors inducing luteolysis. Although the agents causing regression of the CL in a non-fertile cycle are not yet known, intra-luteal growth factors and cytokines that modify the action of LH probably contribute to the reduction of StAR expression and the subsequent fall in progesterone production. PMID:11900886

  8. Luteal blood flow and luteal function

    PubMed Central

    Takasaki, Akihisa; Tamura, Hiroshi; Taniguchi, Ken; Asada, Hiromi; Taketani, Toshiaki; Matsuoka, Aki; Yamagata, Yoshiaki; Shimamura, Katsunori; Morioka, Hitoshi; Sugino, Norihiro

    2009-01-01

    Background Blood flow in the corpus luteum (CL) is associated with luteal function. The present study was undertaken to investigate whether luteal function can be improved by increasing CL blood flow in women with luteal phase defect (LFD). Methods Blood flow impedance in the CL was measured by transvaginal color-pulsed-Doppler-ultrasonography and was expressed as a resistance index (RI). The patients with both LFD [serum progesterone (P) concentrations < 10 ng/ml during mid-luteal phase] and high CL-RI (≥ 0.51) were given vitamin-E (600 mg/day, n = 18), L-arginine (6 g/day, n = 14) as a potential nitric oxide donor, melatonin (3 mg/day, n = 13) as an antioxidant, or HCG (2,000 IU/day, n = 10) during the subsequent menstrual cycle. Results In the control group (n = 11), who received no medication to increase CL blood flow, only one patient (9%) improved in CL-RI and 2 patients (18%) improved in serum P. Vitamin-E improved CL-RI in 15 patients (83%) and improved serum P in 12 patients (67%). L-arginine improved CL-RI in all the patients (100%) and improved serum P in 10 patients (71%). HCG improved CL-RI in all the patients (100%) and improved serum P in 9 patients (90%). Melatonin had no significant effect. Conclusion Vitamin-E or L-arginine treatment improved luteal function by decreasing CL blood flow impedance. CL blood flow is a critical factor for luteal function. PMID:19144154

  9. Matrix metalloproteinase expression and activity following prostaglandin F(2 alpha)-induced luteolysis.

    PubMed

    Ricke, William A; Smith, George W; Smith, Michael F

    2002-03-01

    Luteal tissue contains matrix metalloproteinases (MMPs) that cleave specific components of the extracellular matrix (ECM) and are inhibited by tissue inhibitors of metalloproteinases (TIMPs). We previously reported a decrease in luteal TIMP-1 within 15 min of prostaglandin F(2 alpha) (PGF(2 alpha))-induced luteolysis. An increase in the MMP:TIMP ratio may promote ECM degradation and apoptosis, as observed in other tissues that undergo involution. The objectives of these experiments were to determine whether 1) PGF(2 alpha) affects expression of mRNA encoding fibrillar collagenases (MMP-1 and -13), gelatinases A and B (MMP-2 and -9), membrane type (mt)-1 MMP (MMP-14), stromelysin (MMP-3), and matrilysin (MMP-7), and 2) PGF(2 alpha) increases MMP activity during PGF(2 alpha)-induced luteolysis in sheep. Corpora lutea (n = 3-10/time point) were collected at 0, 15, and 30 min and 1, 2, 4, 6, 12, 24, and 48 h after PGF(2 alpha) administration. Northern blot analysis confirmed the presence of all MMPs except MMP-9. Expression of mRNA for the above MMPs (except MMP-2) increased significantly (P < 0.05) by 30 min, and all MMPs increased significantly (P < 0.05) by 6 h after PGF(2 alpha) administration. Expression of MMP-14 mRNA increased significantly (P < 0.05) by 15 min post-PGF(2 alpha) and remained elevated through 48 h. MMP activity in luteal homogenates (following proenzyme activation and inactivation of inhibitors) was increased significantly (P < 0.05) by 15 min and remained elevated through 48 h post-PGF(2 alpha). MMP activity was localized (in situ zymography) to the pericellular area of various cell types in the 0-h group and was markedly increased by 30 min post-PGF(2 alpha). MMP mRNA expression and activity were significantly increased following PGF(2 alpha) treatment. Increased MMP activity may promote ECM degradation during luteolysis.

  10. Progesterone vaginal ring for luteal support.

    PubMed

    Stadtmauer, Laurel; Waud, Kay

    2015-02-01

    Progesterone supplementation is universally used and has been shown to be beneficial in supplementation of the luteal phase in IVF. There are multiple options and the most commonly used include intramuscular and vaginal progesterone. A progesterone vaginal ring is a novel system for luteal support with advantages of controlled release with less frequent dosing. This review examines options for progesterone luteal support focusing on the rationale for a progesterone vaginal ring. Pub-med search of the literature. A weekly vaginal ring, although not yet FDA approved, is an effective and safe alternative for luteal supplementation in IVF. Large prospective clinical trials are needed to determine the best protocols for replacement cycles.

  11. Alternate Alpha Induced Reactions for NIF Radiochemistry

    SciTech Connect

    Shaughnessy, D A; Moody, K J; Bernstein, L A

    2010-02-26

    Radiochemical analysis of NIF capsule residues has been identified as a potential diagnostic of NIF capsule performance. In particular, alpha-induced nuclear reactions that occur on tracer elements added to the NIF capsule have been shown through simulation to be a very sensitive diagnostic for mix. The short range of the alpha particles makes them representative of the hot spot where they are created through the fusion of deuterium and tritium. Reactions on elements doped into the innermost part of the capsule ablator would therefore be sensitive to material that had mixed into the hot spot. Radiochemical determinations of activated detector elements may perhaps be the only true measure of mix that occurs in a NIF capsule, particularly in cases when the capsule fails.

  12. Mechanisms of reduced luteal sensitivity to prostaglandin F2alpha during maternal recognition of pregnancy in ewes.

    PubMed

    Costine, Beth A; Inskeep, E Keith; Blemings, Kenneth P; Flores, Jorge A; Wilson, Matthew E

    2007-02-01

    During maternal recognition of pregnancy, the conceptus stimulates endometrial secretion of PGF2alpha and PGE2. However, PGF2alpha is less effective in causing luteal regression in pregnant than in non-pregnant ewes. Experiments were conducted to elucidate mechanisms for reduced luteal sensitivity to PGF2alpha during maternal recognition of pregnancy. Corpora lutea (CL) were collected from pregnant and non-pregnant ewes 0, 4, or 12h following treatment with PGF2alpha on day 12 after estrus. Luteal PTGHS2 mRNA did not differ due to PGF2alpha or pregnancy status. Luteal PTGES mRNA was reduced in both pregnant and non-pregnant ewes after PGF2alpha treatment; while, luteal PTGFS mRNA was reduced 4h after PGF2alpha in pregnant, but not non-pregnant ewes. The result was a greater ratio of PTGES to PTGFS mRNA in pregnant ewes. Luteal mRNA for HPGD did not differ between pregnant and non-pregnant ewes on day 12. Luteal END1 mRNA was reduced in pregnant as compared to non-pregnant ewes prior to PGF2alpha challenge. Luteal END1 mRNA was increased after PGF2alpha in pregnant and non-pregnant ewes; however, ECE1 mRNA was reduced 4h after PGF2alpha in pregnant, but not non-pregnant ewes. The in vitro conversion of PGF2alpha to PGFM was greater in CL of pregnant than non-pregnant ewes at day 14. Luteal conversion of PGF2alpha to PGFM appears to be regulated post-transcriptionally. During maternal recognition of pregnancy, mechanisms of reduced luteal sensitivity to PGF2alpha may include a shift in prostaglandin production to the luteotropin PGE2, a reduction of ECE1 mRNA, and increased catabolism of PGF2alpha. PMID:16524686

  13. Gestating for 22 months: luteal development and pregnancy maintenance in elephants

    PubMed Central

    Lueders, Imke; Niemuller, Cheryl; Rich, Peter; Gray, Charlie; Hermes, Robert; Goeritz, Frank; Hildebrandt, Thomas B.

    2012-01-01

    The corpus luteum, a temporally established endocrine gland, formed on the ovary from remaining cells of the ovulated follicle, plays a key role in maintaining the early mammalian pregnancy by secreting progesterone. Despite being a monovular species, 2–12 corpora lutea (CLs) were found on the elephant ovaries during their long pregnancy lasting on average 640 days. However, the function and the formation of the additional CLs and their meaning remain unexplained. Here, we show from the example of the elephant, the close relationship between the maternally determined luteal phase length, the formation of multiple luteal structures and their progestagen secretion, the timespan of early embryonic development until implantation and maternal recognition. Through three-dimensional and Colour Flow ultrasonography of the ovaries and the uterus, we conclude that pregnant elephants maintain active CL throughout gestation that appear as main source of progestagens. Two LH peaks during the follicular phase ensure the development of a set of 5.4 ± 2.7 CLs. Accessory CLs (acCLs) form prior to ovulation after the first luteinizing hormone (LH) peak, while the ovulatory CL (ovCL) forms after the second LH peak. After five to six weeks (the normal luteal phase lifespan), all existing CLs begin to regress. However, they resume growing as soon as an embryo becomes ultrasonographically apparent on day 49 ± 2. After this time, all pregnancy CLs grow significantly larger than in a non-conceptive luteal phase and are maintained until after parturition. The long luteal phase is congruent with a slow early embryonic development and luteal rescue only starts ‘last minute’, with presumed implantation of the embryo. Our findings demonstrate a highly successful reproductive solution, different from currently described mammalian models. PMID:22719030

  14. Gestating for 22 months: luteal development and pregnancy maintenance in elephants.

    PubMed

    Lueders, Imke; Niemuller, Cheryl; Rich, Peter; Gray, Charlie; Hermes, Robert; Goeritz, Frank; Hildebrandt, Thomas B

    2012-09-22

    The corpus luteum, a temporally established endocrine gland, formed on the ovary from remaining cells of the ovulated follicle, plays a key role in maintaining the early mammalian pregnancy by secreting progesterone. Despite being a monovular species, 2-12 corpora lutea (CLs) were found on the elephant ovaries during their long pregnancy lasting on average 640 days. However, the function and the formation of the additional CLs and their meaning remain unexplained. Here, we show from the example of the elephant, the close relationship between the maternally determined luteal phase length, the formation of multiple luteal structures and their progestagen secretion, the timespan of early embryonic development until implantation and maternal recognition. Through three-dimensional and Colour Flow ultrasonography of the ovaries and the uterus, we conclude that pregnant elephants maintain active CL throughout gestation that appear as main source of progestagens. Two LH peaks during the follicular phase ensure the development of a set of 5.4 ± 2.7 CLs. Accessory CLs (acCLs) form prior to ovulation after the first luteinizing hormone (LH) peak, while the ovulatory CL (ovCL) forms after the second LH peak. After five to six weeks (the normal luteal phase lifespan), all existing CLs begin to regress. However, they resume growing as soon as an embryo becomes ultrasonographically apparent on day 49 ± 2. After this time, all pregnancy CLs grow significantly larger than in a non-conceptive luteal phase and are maintained until after parturition. The long luteal phase is congruent with a slow early embryonic development and luteal rescue only starts 'last minute', with presumed implantation of the embryo. Our findings demonstrate a highly successful reproductive solution, different from currently described mammalian models.

  15. Changes in uterine protein secretion during luteal and follicular phases and detection of phosphatases during luteal phase of estrous cycle in buffaloes (Bubalus bubalis).

    PubMed

    Chandra Roy, Sudhir; Uma Suganthi, R; Ghosh, Jyotirmoy

    2006-04-15

    Changes in uterine proteins during different reproductive states and their functional significance though known in other species have not been established in buffaloes. An attempt has been made to unravel the changes in composition of buffalo uterine secretion with growth and regression of corpora-lutea during early, mid and late luteal and follicular phase of estrous cycle using gel filtration and electrophoresis techniques. Also the phosphatases activities in luteal phase uterine secretions have been studied. Gel filtration chromatography analysis revealed a protein peak in void volume of the column, the intensity of which was more in all the luteal phase samples than follicular phase samples. Alkaline phosphatase was also found eluted in the void volume. The other three uterus-specific peaks (Peaks V-VII) were detected below 13.7 kd molecular weight. There were at least five peaks of acid phosphatases activity in chromatogram. Silver staining of SDS-PAGE gel detected as many as 40 protein bands in the uterine fluid of which nine proteins were glycoproteins. Molecular weight (MW) comparison revealed the major protein band at 66 kd which could be serum albumin. Comparison of uterine proteins with serum protein bands revealed a 93.5 kd glycoprotein in buffalo serum that did not appear in uterine fluid and at least 11 uterus-specific protein bands (506, 470, 241, 114, 49, 38, 33, 26, 19.2, 16, and 14.3 kd). The 38 and 19.2 kd bands were luteal-stage specific. Intense periodic acid Schiff's (PAS) stained bands in uterine proteins compared to serum indicated glycosylation process in endometrial epithelial cells. The study suggested that buffalo uterine secretion contained mainly serum and several uterus-specific proteins of which few were luteal phase specific. Further study on characterizing the unique or most abundant proteins and defining their role in uterine functions would help to address the cause of low reproduction rate in buffaloes. PMID:16213013

  16. Evaluation of bovine luteal blood flow by using color Doppler ultrasonography.

    PubMed

    Lüttgenau, J; Bollwein, H

    2014-04-01

    Since luteal vascularization plays a decisive role for the function of the corpus luteum (CL), the investigation of luteal blood flow (LBF) might give valuable information about the physiology and patho-physiology of the CL. To quantify LBF, usually Power mode color Doppler ultrasonography is used. This method detects the number of red blood cells moving through the vessels and shows them as color pixels on the B-mode image of the CL. The area of color pixels is measured with computer-assisted image analysis software and is used as a semiquantitative parameter for the assessment of LBF. Although Power mode is superior for the evaluation of LBF compared to conventional color Doppler ultrasonography, which detects the velocity of blood cells, it is still not sufficiently sensitive to detect the blood flow in the small vessels in the center of the bovine CL. Therefore, blood flow can only be measured in the bigger luteal vessels in the outer edge of the CL. Color Doppler ultrasonographic studies of the bovine estrous cycle have shown that plasma progesterone (P4) concentration can be more reliably predicted by LBF than by luteal size (LS), especially during the CL regression. During the midluteal phase, cows with low P4 level showed smaller CL, but LBF, related to LS, did not differ between cows with low and high P4 levels. In contrast to non-pregnant cows, a significant rise in LBF was observed three weeks after insemination in pregnant cows. However, LBF was not useful for an early pregnancy diagnosis due to high LBF variation among cows. When the effects of an acute systemic inflammation and exogenous hormones on the CL are examined, the LBF determination is more sensitive than LS assessment. In conclusion, color Doppler ultrasonography of the bovine CL provides additional information on luteal function compared to measurements of LS and plasma P4, but its value as a parameter concerning assessment of fertility in cows has to be clarified.

  17. Corpora lutea of pregnant and pseudopregnant domestic cats reveal similar steroidogenic capacities during the luteal life span.

    PubMed

    Zschockelt, Lina; Amelkina, Olga; Siemieniuch, Marta J; Koster, Stefanie; Jewgenow, Katarina; Braun, Beate C

    2014-10-01

    luteal stages of pseudopregnancy. Concentrations of P4 were higher in the development/maintenance compared to the regression stages (p=0.01). We conclude that cat CL of the same histomorphological stage are characterised by identical steroidogenic capacities independently of an on-going pregnancy. PMID:25138635

  18. Histological and endocrine characterisation of the annual luteal activity in Eurasian lynx (Lynx lynx).

    PubMed

    Carnaby, Kim; Painer, Johanna; Söderberg, Arne; Gavier-Widèn, Dolores; Göritz, Frank; Dehnhard, Martin; Jewgenow, Katarina

    2012-10-01

    Lynx presents a unique sexual cycle with persistent corpora lutea (CLs) and elevated serum progesterone (P₄) throughout parturition and lactation. In other mammals, CLs normally disintegrate after parturition, therefore the aim of our study was to characterise the annual life cycle of lynx CLs. Ovaries from Eurasian lynxes were obtained from the National Veterinary Institute in Sweden, where tissues from killed lynx were stored at -20 °C. Ovaries from 66 animals were weighed; each corpus luteum was segmented for histology and hormone analysis. Ovary and CLs weights were constant throughout the year, peaking during pregnancy. In non-pregnant lynxes, the seasonal level of intraluteal steroids was steady for P₄ (3.2±1.9 s.d. μg/g, n=53) and total oestrogens (18.3±15.5 s.d. ng/g, n=53). Within histology slides, structurally intact luteal cells were found throughout the year with the highest incidence in March/April; evidence of luteal regression was predominantly found in post-breeding season. Ovaries from pregnant animals contained two types of CLs. Group A was bigger in size with large luteal cells (P₄, 72.3±65.4 s.d. μg/g; oestrogen, 454.0±52.4 s.d. ng/g). In contrast, group B were smaller, with greater luteal regression and lower steroid concentrations (P₄, 8.3±2.9 s.d. μg/g; oestrogen, 31.5±20.4 s.d. ng/g). Our results suggest that structural luteolysis proceeds throughout the year and into next breeding cycle, resulting in two CLs types on the same ovary.

  19. Isolation and functional aspects of free luteal cells

    SciTech Connect

    Luborsky, J.L.; Berhrman, H.R.

    1985-01-01

    Methods of luteal cell isolation employ enzymatic treatment of luteal tissue with collagenase and deoxyribonuclease. Additional enzymes such as hyaluronidase or Pronase are also used in some instances. Isolated luteal cells retain the morphological characteristics of steroid secreting cells after isolation. They contain mitochondria, variable amounts of lipid droplets, and an extensive smooth endoplasmic reticulum. Isolated luteal cells have been used in numerous studies to examine the regulation of steriodogenesis by luteinizing hormone (LH). LH receptor binding studies were employed to quantitate specific properties of hormone-receptor interaction in relation to cellular function. Binding of (/sup 125/I)LH to bovine luteal cells and membranes was compared and it was concluded that the enzymatic treatment used to isolate cells did not change the LH receptor binding kinetics.

  20. Leucocyte phagocytosis during the luteal phase in bitches.

    PubMed

    Holst, Bodil Ström; Gustavsson, Malin Hagberg; Lilliehöök, Inger; Morrison, David; Johannisson, Anders

    2013-05-15

    Pyometra is a disease that affects a large proportion of intact bitches, and typically is seen during the latter half of dioestrus. Several factors contribute to the development of pyometra, including genetic factors, an infectious component (most often Escherichia coli), and hormonal factors. Hormones may act directly on the endometrium, and also affect the immune system. In dogs, the phagocytic ability has been shown to decrease with age, and ovarian hormones have also been shown to affect immune resistance. The aim of the present study was to examine whether phagocytosis by canine leucocytes varies significantly during the luteal phase. Eight bitches were followed by repeated blood sampling. Samples were taken at the calculated optimal day for mating (Day 1), and thereafter on days 8, 15 and 22 (early luteal phase) and 29, 43, 57 and 71 (late luteal phase). Blood was collected from the cephalic vein into EDTA tubes for leucocyte counts and heparinised tubes for testing of phagocytosis and oxidative burst using commercial kits and flow cytometry. The cell activity of the phagocyting leucocytes, expressed as mean fluorescence activity, MFI, was significantly lower during late luteal phase than during early luteal phase. The proportion of leucocytes that was induced to phagocyte did not differ significantly. The percentage of cells stimulated by E. coli to oxidative burst was significantly lower during late luteal phase. Their activity did not differ between the two periods. The number of cells stimulated to oxidative burst by a low stimulus was too low to evaluate, and leucocytes stimulated with the high stimulus did not vary in oxidative burst between the two periods. The changes in phagocytic activity and in the number of leucocytes that showed oxidative burst were not associated with any change in the proportion of different leucocytes. The decreased phagocytic capacity possibly contributes to the higher incidence of diseases such as pyometra during the latter

  1. Size distribution of luteal cells during pseudopregnancy in domestic cats.

    PubMed

    Arikan, S; Yigit, A A; Kalender, H

    2009-10-01

    Experiments were designed to investigate the size distribution of queen steroidogenic luteal cells throughout pseudopregnancy. Corpora lutea were obtained from the queens following ovariohysterectomy on days 7, 15 or 25 of pseudopregnancy. Luteal cells were isolated from the ovary by collagenase digestion. Steriodogenic cells were identified by staining of cells for 3beta-HSD activity. Cell diameters were measured using a microscope. Luteal cells having steroidogenic capacity covered a wide spectrum of sizes ranging from 3 to 35 mum in diameter. There was a significant increase in mean cell diameters (p < 0.01) as pseudopregnancy progressed. Mean diameter of 3beta-HSD positive cells increased from 10.41 +/- 0.7 microm, on day 7 of pseudopregnancy, to 19.72 +/- 1.3 microm on day 25 of pseudopregnancy. The ratio of large (>20 microm in diameter) to small (3-20 microm in diameter) luteal cells was 0.08 : 1.0 on day 7 of pseudopregnancy, with the 7.5-10 microm cell size class predominant. By day 25 of pseudopregnancy, the ratio of large-to-small cells was increased to 0.87 : 1.0, and 20-25 microm cell sizes become predominant. In conclusion, this study has demonstrated that the cells of the corpus luteum undergo continuous differentiation during pseudopregnancy in queen. This study also demonstrates that luteal cells dissociated from pseudopregnant queen can be used as a model to study the physiology of corpus luteum in pregnant cats.

  2. Abnormal structural luteolysis in ovaries of the senescence accelerated mouse (SAM): expression of Fas ligand/Fas-mediated apoptosis signaling molecules in luteal cells.

    PubMed

    Kiso, Minako; Manabe, Noboru; Komatsu, Kohji; Shimabe, Munetake; Miyamoto, Hajime

    2003-12-01

    Senescence accelerated mouse-prone (SAMP) mice with a shortened life span show accelerated changes in many of the signs of aging and a shorter reproductive life span than SAM-resistant (SAMR) controls. We previously showed that functional regression (progesterone dissimilation) occurs in abnormally accumulated luteal bodies (aaLBs) of SAMP mice, but structural regression of luteal cells in aaLB is inhibited. A deficiency of luteal cell apoptosis causes the abnormal accumulation of LBs in SAMP ovaries. In the present study, to show the abnormality of Fas ligand (FasL)/Fas-mediated apoptosis signal transducing factors in the aaLBs of the SAMP ovaries, we assessed the changes in the expression of FasL, Fas, caspase-8 and caspase-3 mRNAs by reverse transcription-polymerase chain reaction, and in the expression and localization of FasL, Fas and activated caspase-3 proteins by Western blotting and immunohistochemistry, respectively, during the estrus cycle/luteolysis. These mRNAs and proteins were expressed in normal LBs of both SAMP and SAMR ovaries, but not at all or only in trace amounts in aaLBs of SAMP, indicating that structural regression is inhibited by blockage of the expression of these transducing factors in luteal cells of aaLBs in SAMP mice. PMID:14967896

  3. Tumor necrosis factor alpha-induced pulmonary vascular endothelial injury.

    PubMed Central

    Goldblum, S E; Hennig, B; Jay, M; Yoneda, K; McClain, C J

    1989-01-01

    Tumor necrosis factor alpha (TNF-alpha) mediates components of the acute-phase response, stimulates granulocyte metabolism, and induces endothelial cell surface changes. We studied whether human recombinant TNF-alpha (rTNF-alpha) could increase pulmonary edema formation and pulmonary vascular permeability. Rabbits preinfused with 125I-albumin were administered rTNF-alpha or saline. Animals were sacrificed, and lung wet/dry weight ratios as well as bronchoalveolar lavage fluid and plasma 125I activities were determined. rTNF-alpha increased lung wet/dry weight ratios by 151% (P less than 0.02) and bronchoalveolar lavage fluid/plasma 125I activity ratios by 376% (P less than 0.01) compared with values for saline controls. Electron microscopy of lung sections demonstrated endothelial injury, perivascular edema, and extravasation of an ultrastructural permeability tracer. To demonstrate that rTNF-alpha could directly increase pulmonary vascular endothelial permeability in vitro, we studied albumin transfer across cultured porcine pulmonary artery endothelial cell monolayers. rTNF-alpha induced time-dependent dose-response increments in transendothelial albumin flux in the absence of granulocyte effector cells. These observations suggest that rTNF-alpha can provoke acute pulmonary vascular endothelial injury in vivo as well as in vitro. Images PMID:2925247

  4. Interferon-alpha induces transient upregulation of c-FLIP through NF-kappaB activation.

    PubMed

    Kanetaka, Yuki; Hayashida, Miho; Hoshika, Akinori; Yanase, Noriko; Mizuguchi, Junichiro

    2008-01-15

    Interferon-alpha (IFN-alpha) induces apoptosis in some cell types and promotes cell survival in other cell types, but the molecular mechanisms underlying distinct IFN-alpha-induced cell behaviours remain poorly understood. In the present study, we show that IFN-alpha induced the cellular FLICE (FADD-like interleukin-1 beta-converting enzyme) inhibitory protein (c-FLIP), which serves as a promoter of cell survival in human B lymphoma cells. IFN-alpha induction of transient upregulation of c-FLIP was partially abrogated by the NF-kappaB inhibitor BAY11-7082 (BAY). Pretreatment with BAY sensitized both Daudi and U266 cells to the IFN-alpha-induced loss of mitochondrial membrane potential (DeltaPsi(m)). IFN-alpha phosphorylated the PKC isoform PKCalpha at a threonine residue, and the PKCalpha/betaI inhibitor Go6976 abrogated upregulation of IFN-alpha-induced NF-kappaB activity, leading to sensitization of cells to IFN-alpha-induced apoptosis. To analyze the role of PKCalpha in the IFN-alpha-induced signaling, Daudi cells overexpressing a constitutively active mutant of PKCalpha (caPKCalpha) were used. The caPKCalpha-expressing Daudi cells were partially resistant to the IFN-alpha-induced loss of DeltaPsi(m), concomitant with elevated levels of c-FLIP protein. Together, these results demonstrate that IFN-alpha causes a transient upregulation of c-FLIP expression, at least through PKCalpha-mediated activation of NF-kappaB. The balance between IFN-alpha-induced pro-apoptotic and survival signals determines the cell fate. Thus, therapeutic intervention in this balance may be effective for treatment of patients with IFN-alpha-refractory tumours.

  5. Alpha Induced Reaction Cross Section Calculations of Tantalum Nucleus

    NASA Astrophysics Data System (ADS)

    Tel, E.; Ugur, F. A.; Gokce, A. A.

    2013-04-01

    The fusion energy is attractive as an energy source because the fusion will not produce CO2 or SO2 and so fusion will not contribute to environmental problems, such as particulate pollution and excessive CO2 in the atmosphere. The fusion reaction does not produce radioactive nuclides and it is not self-sustaining, as is a fission reaction when a critical mass of fissionable material is assembled. Since the fusion reaction is easily and quickly quenched the primary sources of heat to drive such an accident are heat from radioactive decay and heat from chemical reactions. Both the magnitude and time dependence of the generation of heat from radioactive decay can be controlled by proper selection and design of materials. Tantalum is one of the candidate materials for the first wall of fusion reactors and for component parts of irradiation chambers. Accurate experimental cross-section data of alpha induced reactions on Tantalum are also of great importance for thermonuclear reaction rate determinations since the models used in the study of stellar nucleosynthesis are strongly dependent on these rates (Santos et al. in J Phys G 26:301, 2000). In this study, neutron-production cross sections for target nuclei 181Ta have been investigated up to 100 MeV alpha energy. The excitation functions for (α, xn) reactions (x = 1, 2, 3) have been calculated by pre-equilibrium reaction mechanism. And also neutron emission spectra for 181Ta (α, xn) reactions at 26.8 and 45.2 MeV have been calculated. The mean free path multiplier parameters has been investigated. The pre-equilibrium results have been calculated by using the hybrid model, the geometry dependent hybrid (GDH) model. Calculation results have been also compared with the available measurements in literature.

  6. Prostaglandin F2 alpha stimulates phosphatidylinositol 4,5-bisphosphate hydrolysis and mobilizes intracellular Ca2+ in bovine luteal cells.

    PubMed Central

    Davis, J S; Weakland, L L; Weiland, D A; Farese, R V; West, L A

    1987-01-01

    The present studies were conducted to determine whether prostaglandin F2 alpha (PGF2 alpha) stimulates the production of "second messengers" derived from inositol phospholipid hydrolysis and increases intracellular free Ca2+ ([Ca2+]i) in isolated bovine luteal cells. PGF2 alpha provoked rapid (10 sec) and sustained (up to 60 min) increases in the levels of inositol mono-, bis-, and trisphosphates (InsP, InsP2, and InsP3, respectively). InsP3 was formed more rapidly than InsP2 or InsP after PGF2 alpha treatment. In addition, PGF2 alpha increased inositol phospholipid turnover, as evidenced by increased 32PO4 incorporation into phosphatidic acid and phosphatidylinositol. LiCl (1-20 mM) enhanced inositol phosphate accumulation in response to PGF2 alpha. Maximal increases in InsP3 occurred at 1 microM PGF2 alpha, with half-maximal stimulation occurring at 36 nM. The acute effects of PGF2 alpha on InsP3 levels were independent of reductions in extracellular calcium. Prostaglandins E1 and E2 also stimulated increases in inositol phosphate levels, albeit to a lesser extent. PGF2 alpha also induced rapid and concentration-dependent increases in [Ca2+]i as measured by quin-2 fluorescence. The PGF2 alpha-induced increases in [Ca2+]i were maximal within 30 sec (approximately 2- to 3-fold), and [Ca2+]i remained elevated for 8-10 min. The PGF2 alpha-induced increases in [Ca2+]i were also independent of extracellular calcium. These findings demonstrate that the action of PGF2 alpha is coupled to the phospholipase C-InsP3 and diacylglycerol second messenger system in the corpus luteum. PMID:3035550

  7. Luteal versus follicular phase surgical oophorectomy plus tamoxifen in premenopausal women with metastatic hormone receptor positive breast cancer

    PubMed Central

    Love, Richard R.; Hossain, Syed Mozammel; Hussain, Md. Margub; Mostafa, Mohammad Golam; Laudico, Adriano V.; Siguan, Stephen Sixto S.; Adebamowo, Clement; Sun, Jing-zhong; Fei, Fei; Shao, Zhi-Ming; Yunjiang, Liu; Akram Hussain, Syed Md.; Zhang, Baoning; Lin, Cheng; Panigaro, Sonar; Walta, Fardiana; Chuan, Jiang Hong; Mirasol-Lumague, Maria Rica; Yip, Cheng-Har; Navarro, Narciso S.; Huang, Chiun-sheng; Lu, Yen-shen; Ferdousy, Tahmina; Salim, Reza; Akhter, Chameli; Nahar, Shamsun; Uy, Gemma; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

    2016-01-01

    Purpose In premenopausal women with metastatic hormone receptor positive breast cancer, hormonal therapy is the first line therapy. GnRH + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favorably influenced long-term outcomes. Methods 249 premenopausal women with incurable or metastatic hormone receptor positive breast cancer entered a trial in which they were randomized to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression free survival in the two randomized groups and by hormone confirmed menstrual cycle phase. Results Overall survival (OS) and progression-free survival were not demonstrated to be different in the two randomized groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels of <2ng/ml (anovulatory patients) (adjusted hazard ratio 1.46, 95% CI: 0.89–2.41, p=0.14) compared to patients in luteal phase with progesterone 2ng/ml or higher. Median overall survival was 2.0 years (95% CI: 1.7 – 2.3) and OS at 4 years was 26%. Conclusions The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT 00293540 PMID:27107325

  8. Luteal development and progesterone levels during pregnancy of the viviparous temperate lizard Barisia imbricata imbricata (Reptilia: Anguidae).

    PubMed

    Martínez-Torres, Martín; Elena Hernández-Caballero, Marta; Alvarez-Rodriguez, Carmen; Alba Luis-Díaz, Juana; Ortíz-López, Guadalupe

    2003-06-01

    The relationship between plasma progesterone (P(4)) levels and the formation and degeneration of the corpus luteum (CL) was assessed monthly during gestation of the viviparous lizard Barisia imbricata imbricata. Histochemical activity of the delta(5-4) isomerase 3 beta-hydroxysteroide dehydrogenase (delta(5-4)3beta-HSD) in the luteal tissue and embryonic development were also observed. Females were gravid throughout winter and great part of spring (late November or early December until late May or early June). Corpus luteum development occurred in the first third of gestation (December and January) when the embryo reached developmental stage 27. Four sequential stages were identified during development and three stages during regression of the CL. The follicular and thecal tissue participated in the formation of the luteal cell mass. According to Xavier's classification, the CL of B. i. imbricata is a subtype from Type III. The activity of delta(5-4)3beta-HSD was observed mainly in the luteal cell mass. The first degenerative changes in the CL were observed in the early second third of the gestation and continued gradually until parturition. Progesterone levels increased in early pregnancy and reached its highest level during January (3.07+/-1.04 ng/ml) when mature corpora lutea were present. Gradual diminution in progesterone concentrations occurred in the second and last third of pregnancy and coincided with advanced degenerative changes and diminution in histochemical activity of delta(5-4)3beta-HSD in the luteal tissue. These observations suggest that the CL is the major source of progesterone during pregnancy of B. i. imbricata.

  9. Endoplasmic reticulum stress-mediated apoptotic pathway is involved in corpus luteum regression in rats.

    PubMed

    Yang, Yanzhou; Sun, Miao; Shan, Yuanyuan; Zheng, Xiaomin; Ma, Huiming; Ma, Wenzhi; Wang, Zhisheng; Pei, Xiuying; Wang, Yanrong

    2015-05-01

    Endoplasmic reticulum stress (ERS), which is a novel pathway of regulating cellular apoptosis and the function of ERS during corpus luteum (CL) regression, is explored. Early-luteal stage (day 2), mid-luteal stage (day 7), and late-luteal stage (day 14 and 20) were induced, and the apoptosis of luteal cells was detected by a terminal 2'-deoxyuridine 5'-triphosphate nick-end labeling (TUNEL) assay. The apoptotic cells were increased with the regression of CL, especially during the late-luteal stage. The ERS markers glucose-regulated protein 78 (Grp78), CCAAT/enhancer-binding protein homologous protein (CHOP), X-box binding protein 1 (XBP1), activating transcription factor 6α (ATF6α), eukaryotic initiation factor 2α (eIF2α), inositol-requiring protein 1α (IRE1α), caspase 12, and apoptosis marker caspase 3 were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry, in agreement with the results of the TUNEL assay; the expression levels of CHOP, caspase 12, and caspase 3 were increased during the process of CL regression. Luteal cells were isolated and cultured in vitro, and the apoptosis of luteal cells was induced by prostaglandin F2α. The ERS was attenuated by the ERS inhibitor tauroursodeoxycholic acid, and the apoptotic rate was analyzed by flow cytometry. The ERS markers Grp78, CHOP, XBP1s, ATF6α, eIF2α, IRE1α, caspase 12, and apoptotic execute marker caspase 3 were analyzed by real-time PCR and immunofluorescence, and the results suggested that the expression of CHOP, caspase 12, and caspase 3 were increased, and there was increased apoptosis of luteal cells. But the expression of IRE1α/XBP1s and eIF2α was not detected. Taken together, the ERS is involved in the CL regression of rats through the CHOP and caspase 12 pathway.

  10. Endoplasmic Reticulum Stress-Mediated Apoptotic Pathway Is Involved in Corpus Luteum Regression in Rats

    PubMed Central

    Yang, Yanzhou; Sun, Miao; Shan, Yuanyuan; Zheng, Xiaomin; Ma, Huiming; Ma, Wenzhi; Wang, Zhisheng

    2015-01-01

    Endoplasmic reticulum stress (ERS), which is a novel pathway of regulating cellular apoptosis and the function of ERS during corpus luteum (CL) regression, is explored. Early-luteal stage (day 2), mid-luteal stage (day 7), and late-luteal stage (day 14 and 20) were induced, and the apoptosis of luteal cells was detected by a terminal 2′-deoxyuridine 5′-triphosphate nick-end labeling (TUNEL) assay. The apoptotic cells were increased with the regression of CL, especially during the late-luteal stage. The ERS markers glucose-regulated protein 78 (Grp78), CCAAT/enhancer-binding protein homologous protein (CHOP), X-box binding protein 1 (XBP1), activating transcription factor 6α (ATF6α), eukaryotic initiation factor 2α (eIF2α), inositol-requiring protein 1α (IRE1α), caspase 12, and apoptosis marker caspase 3 were analyzed by real-time polymerase chain reaction (PCR) and immunohistochemistry, in agreement with the results of the TUNEL assay; the expression levels of CHOP, caspase 12, and caspase 3 were increased during the process of CL regression. Luteal cells were isolated and cultured in vitro, and the apoptosis of luteal cells was induced by prostaglandin F2α. The ERS was attenuated by the ERS inhibitor tauroursodeoxycholic acid, and the apoptotic rate was analyzed by flow cytometry. The ERS markers Grp78, CHOP, XBP1s, ATF6α, eIF2α, IRE1α, caspase 12, and apoptotic execute marker caspase 3 were analyzed by real-time PCR and immunofluorescence, and the results suggested that the expression of CHOP, caspase 12, and caspase 3 were increased, and there was increased apoptosis of luteal cells. But the expression of IRE1α/XBP1s and eIF2α was not detected. Taken together, the ERS is involved in the CL regression of rats through the CHOP and caspase 12 pathway. PMID:25332219

  11. Endocrine disruptors and human corpus luteum: in vitro effects of phenols on luteal cells function.

    PubMed

    Romani, Federica; Tropea, Anna; Scarinci, Elisa; Dello Russo, Cinzia; Lisi, Lucia; Catino, Stefania; Lanzone, Antonio; Apa, Rosanna

    2013-01-01

    Endocrine disruptors are well known to impair fertility. The aim of the present study was to investigate the effects of bisphenol A (BPA) and nonylphenol (p-NP) on human luteal function in vitro. In particular, in luteal cells isolated from 21 human corpora lutea progesterone, prostaglandin (PG) F2α, PGE2 and vascular endothelial growth factor (VEGF) release, as well as VEGF expression were evaluated. BPA and p-NP negatively affected both luteal steroidogenesis and luteotrophic/ luteolytic factors balance, without influencing VEGF mRNA expression. Actually, BPA and p-NP impaired human luteal cells function in vitro, underlining the already suggested correlation between phenols and reproductive failure.

  12. Expression and localization of insulin-like growth factor system in corpus luteum during different stages of estrous cycle in water buffaloes (Bubalus bubalis) and the effect of insulin-like growth factor I on production of vascular endothelial growth factor and progesterone in luteal cells cultured in vitro.

    PubMed

    Uniyal, S; Panda, R P; Chouhan, V S; Yadav, V P; Hyder, I; Dangi, S S; Gupta, M; Khan, F A; Sharma, G T; Bag, S; Sarkar, M

    2015-01-01

    This study investigated the expression and localization of insulin-like growth factor (IGF) system at different stages of buffalo CL and the role of IGF-I in stimulating vascular endothelial growth factor (VEGF) and progesterone (P4) production in cultured luteal cells. The mRNA expression of IGF system, VEGF, steroidogenic acute regulatory protein, P450scc, and hydroxysteroid dehydrogenase (HSD) was investigated by quantitative real-time polymerase chain reaction (PCR). Protein expression of IGF was demonstrated by Western blot and localization by immunohistochemistry. Progesterone and VEGF production was assayed using RIA and ELISA. A relatively high mRNA expression of IGF-I and IGF-II in early, mid- and late luteal phases with immunoreactivity mostly restricted to cytoplasm of large luteal cells indicates their autocrine role, whereas very weak immunoreactivity in endothelial cells during the mid-luteal phase indicates their paracrine role. Insulin-like growth factor receptors, IGF-IR and IGF-IIR, were restricted to large luteal cells with high mRNA and protein expressions in the mid-luteal phase. The significantly higher expression of insulin-like growth factor binding protein (IGFBP)-1, -3, -5, and -6 in the early or mid-luteal phase suggested their stimulatory role, whereas that of IGFBP-2 and -4 in mid-, late, and regressive luteal stages implied their inhibitory role. The mRNA expressions of key steroidogenic factors and VEGF were significantly higher (P < 0.05) when the culture medium was supplemented with 100 ng/mL of IGF-I for 72 hours. Moreover, IGF-I at a dose of 100 ng/mL increased P4 and VEGF production (P < 0.05). It can be concluded that IGF family members via their autocrine and paracrine effect play significant roles in promoting angiogenesis through the production of VEGF in luteal cells and steroid synthesis through the production of key steroidogenic factors.

  13. Anti-inflammatory effect of resveratrol on TNF-{alpha}-induced MCP-1 expression in adipocytes

    SciTech Connect

    Zhu Jian; Yong Wei; Wu Xiaohong; Yu Ying; Lv Jinghuan; Liu Cuiping; Mao Xiaodong; Zhu Yunxia; Xu Kuanfeng; Han Xiao Liu Chao

    2008-05-02

    Chronic low-grade inflammation characterized by adipose tissue macrophage accumulation and abnormal cytokine production is a key feature of obesity and type 2 diabetes. Adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, induced by cytokines, has been shown to play an essential role in the early events during macrophage infiltration into adipose tissue. In this study we investigated the effects of resveratrol upon both tumor necrosis factor (TNF)-{alpha}-induced MCP-1 gene expression and its underlying signaling pathways in 3T3-L1 adipoctyes. Resveratrol was found to inhibit TNF-{alpha}-induced MCP-1 secretion and gene transcription, as well as promoter activity, which based on down-regulation of TNF-{alpha}-induced MCP-1 transcription. Nuclear factor (NF)-{kappa}B was determined to play a major role in the TNF-{alpha}-induced MCP-1 expression. Further analysis showed that resveratrol inhibited DNA binding activity of the NF-{kappa}B complex and subsequently suppressed NF-{kappa}B transcriptional activity in TNF-{alpha}-stimulated cells. Finally, the inhibition of MCP-1 may represent a novel mechanism of resveratrol in preventing obesity-related pathologies.

  14. Profiling of Luteal Transcriptome during Prostaglandin F2-Alpha Treatment in Buffalo Cows: Analysis of Signaling Pathways Associated with Luteolysis

    PubMed Central

    Suganthi, Hepziba; Rudraiah, Medhamurthy

    2014-01-01

    In several species including the buffalo cow, prostaglandin (PG) F2α is the key molecule responsible for regression of corpus luteum (CL). Experiments were carried out to characterize gene expression changes in the CL tissue at various time points after administration of luteolytic dose of PGF2α in buffalo cows. Circulating progesterone levels decreased within 1 h of PGF2α treatment and evidence of apoptosis was demonstrable at 18 h post treatment. Microarray analysis indicated expression changes in several of immediate early genes and transcription factors within 3 h of treatment. Also, changes in expression of genes associated with cell to cell signaling, cytokine signaling, steroidogenesis, PG synthesis and apoptosis were observed. Analysis of various components of LH/CGR signaling in CL tissues indicated decreased LH/CGR protein expression, pCREB levels and PKA activity post PGF2α treatment. The novel finding of this study is the down regulation of CYP19A1 gene expression accompanied by decrease in expression of E2 receptors and circulating and intra luteal E2 post PGF2α treatment. Mining of microarray data revealed several differentially expressed E2 responsive genes. Since CYP19A1 gene expression is low in the bovine CL, mining of microarray data of PGF2α-treated macaques, the species with high luteal CYP19A1 expression, showed good correlation between differentially expressed E2 responsive genes between both the species. Taken together, the results of this study suggest that PGF2α interferes with luteotrophic signaling, impairs intra-luteal E2 levels and regulates various signaling pathways before the effects on structural luteolysis are manifest. PMID:25102061

  15. Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss

    PubMed Central

    Jukic, Anne Marie; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.; Calafat, Antonia M.; McConnaughey, D. Robert; Longnecker, Matthew P.; Hoppin, Jane A.; Weinberg, Clarice R.; Wilcox, Allen J.; Baird, Donna D.

    2015-01-01

    Background Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss. Objectives We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy. Methods Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss. Results Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: –0.5 days (95% CI: –0.9, –0.1), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: –0.8 days (95% CI: –1.2, –0.4), 3rd vs. 1st: –0.4 days (95% CI: –0.8, 0.02), p = 0.001]. Conclusions BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle–specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies. Citation Jukic

  16. Omentin inhibits TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via ERK/NF-{kappa}B pathway

    SciTech Connect

    Zhong, Xia; Li, Xiaonan; Liu, Fuli; Tan, Hui; Shang, Deya

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Black-Right-Pointing-Pointer Omentin reduces expression of ICAM-1 and VCAM-1 induced by TNF-{alpha} in HUVECs. Black-Right-Pointing-Pointer Omentin inhibits TNF-{alpha}-induced ERK and NF-{kappa}B activation in HUVECs. Black-Right-Pointing-Pointer Omentin supreeses TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 via ERK/NF-{kappa}B pathway. -- Abstract: In the present study, we investigated whether omentin affected the expression of intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in tumor necrosis factor-{alpha} (TNF-{alpha}) induced human umbilical vein endothelial cells (HUVECs). Our data showed that omentin decreased TNF-{alpha}-induced expression of ICAM-1 and VCAM-1 in HUVECs. In addition, omentin inhibited TNF-{alpha}-induced adhesion of THP-1 cells to HUVECs. Further, we found that omentin inhibited TNF-{alpha}-activated signal pathway of nuclear factor-{kappa}B (NF-{kappa}B) by preventing NF-{kappa}B inhibitory protein (I{kappa}B{alpha}) degradation and NF-{kappa}B/DNA binding activity. Omentin pretreatment significantly inhibited TNF-{alpha}-induced ERK activity and ERK phosphorylation in HUVECs. Pretreatment with PD98059 suppressed TNF-{alpha}-induced NF-{kappa}B activity. Omentin, NF-kB inhibitor (BAY11-7082) and ERK inhibitor (PD98059) reduced the up-regulation of ICAM-1 and VCAM-1 induced by TNF-{alpha}. These results suggest that omentin may inhibit TNF-{alpha}-induced expression of adhesion molecules in endothelial cells via blocking ERK/NF-{kappa}B pathway.

  17. The luteal heat cycle of the breast in health.

    PubMed

    Simpson, H W; Griffiths, K; McArdle, C; Pauson, A W; Hume, P; Turkes, A

    1993-09-01

    Wearing a special thermometric brassiere, twenty-five normal women self-measured their breast surface temperature. The subjects averaged 39 years of age and all were parous. Observations were made for one hour each evening for one menstrual cycle under semi-standardized domestic conditions. They also collected daily samples of saliva for radioimmunoassay of progesterone concentration. The surface temperature of the breast is relatively cold around mid-cycle; thereafter, and without interruption in averaged data, the temperature increases steadily by about 1 degree C over the 12 days of the luteal phase; around the time of the menses, it falls rapidly. This heat rhythm does not occur in peri-menopausal low progesterone menstrual cycles or in patients where the breast tissue has been irradiated for cancer treatment.

  18. Luteal activity of pregnant rats with hypo-and hyperthyroidism

    PubMed Central

    2014-01-01

    Background Luteal activity is dependent on the interaction of various growth factors, cytokines and hormones, including the thyroid hormones, being that hypo- and hyperthyroidism alter the gestational period and are also a cause of miscarriage and stillbirth. Because of that, we evaluated the proliferation, apoptosis and expression of angiogenic factors and COX-2 in the corpus luteum of hypo- and hyperthyroid pregnant rats. Methods Seventy-two adult female rats were equally distributed into three groups: hypothyroid, hyperthyroid and control. Hypo- and hyperthyroidism were induced by the daily administration of propylthiouracil and L-thyroxine, respectively. The administration began five days before becoming pregnant and the animals were sacrificed at days 10, 14, and 19 of gestation. We performed an immunohistochemical analysis to evaluate the expression of CDC-47, VEGF, Flk-1 (VEGF receptor) and COX-2. Apoptosis was evaluated by the TUNEL assay. We assessed the gene expression of VEGF, Flk-1, caspase 3, COX-2 and PGF2α receptor using real time RT-PCR. The data were analyzed by SNK test. Results Hypothyroidism reduced COX-2 expression on day 10 and 19 (P < 0.05), endothelial/pericyte and luteal cell proliferation on day 10 and 14 (p < 0.05), apoptotic cell numbers on day 19 (p < 0.05) and the expression of Flk-1 and VEGF on day 14 and 19, respectively (p < 0.05). Hyperthyroidism increased the expression of COX-2 on day 19 (P < 0.05) and the proliferative activity of endothelial/pericytes cells on day 14 (p <0.05), as well as the expression of VEGF and Flk-1 on day 19 (P < 0.05). Conclusions Hypothyroidism reduces the proliferation, apoptosis and expression of angiogenic factors and COX-2in the corpus luteum of pregnant rats, contrary to what is observed in hyperthyroid animals, being this effect dependent of the gestational period. PMID:25298361

  19. Systematic Determination of Differential Gene Expression in the Primate Corpus Luteum during the Luteal Phase of the Menstrual Cycle

    PubMed Central

    Bogan, Randy L.; Murphy, Melinda J.; Stouffer, Richard L.; Hennebold, Jon D.

    2008-01-01

    The molecular and cellular processes required for development, function, and regression of the primate corpus luteum (CL) are poorly defined. We hypothesized that there are dynamic changes in gene expression occurring during the CL life span, which represent proteins and pathways critical to its regulation. Therefore, a genomic approach was utilized to systematically identify differentially expressed genes in the rhesus macaque CL during the luteal phase of natural menstrual cycles. CL were collected between d 3–5 (early stage), d 7–8 (mid), d 10–12 (mid-late), d 14–16 (late), or d 18–19 (very-late) after the midcycle LH surge. From the early through very-late stages, 3234 transcripts were differentially expressed, with 879 occurring from the early through late stages that encompass the processes of luteinization, maintenance, and functional regression. To characterize gene changes most relevant to these processes, ontology analysis was performed using the list of 879 differentially expressed transcripts. Four main groups of related genes were identified with relevance to luteal physiology including: 1) immune function; 2) hormone and growth factor signaling; 3) steroidogenesis; and 4) prostaglandin biosynthesis, metabolism, and signaling. A subset of genes representing each of the four major categories was selected for validation of microarray results by quantitative real-time PCR. Results in mRNA levels were similar between the two methodologies for 17 of 18 genes. Additionally, protein levels for three genes were determined by Western blot analysis to parallel mRNA levels. This database will facilitate the identification of many novel or previously underappreciated pathways that regulate the structure and function of the primate CL. PMID:18258683

  20. Lipid droplets in cultured luteal cells in non-pregnant sheep fed different planes of nutrition.

    PubMed

    Khanthusaeng, Vilaivan; Thammasiri, Jiratti; Bass, Casie S; Navanukraw, Chainarong; Borowicz, Pawel; Redmer, Dale A; Grazul-Bilska, Anna T

    2016-07-01

    Accumulation of lipid droplets (LD) in luteal cells likely is important for energy storage and steroidogenesis in the highly metabolically active corpus luteum (CL). The objective of this study was to determine the effect of plane of nutrition on progesterone (P4) secretion, and lipid droplet number and size in cultured ovine luteal cells. Ewes were randomly assigned to one of three nutritional groups: control (C; 100% NRC requirements, n=9), overfed (O; 2×C, n=12), or underfed (U; 0.6×C, n=10). Superovulation was induced by follicle stimulating hormone injections. At the early and mid-luteal phases of the estrous cycle, CL were dissected from ovaries, and luteal cells isolated enzymatically. Luteal cells were incubated overnight in medium containing serum in chamber slides. Media were then changed to serum-free and after 24h incubation, media were collected for P4 analysis, and cells were fixed in formalin and stained with BODIPY followed by DAPI staining. Z-stacks of optical sections of large and small luteal cells (LLC and SLC, respectively) were obtained using a laser-scanning microscope. Rendered 3D images of individual LLC and SLC were analyzed for cell volume, and total and individual LD volume, number and percentage of cellular volume occupied by LD by using Imaris software. Concentrations of P4 in serum and media were greater (P<0.05) at the mid than early-luteal phase, and were not affected by nutritional plane. LD total volume and number were greater (P<0.001) in LLC than SLC; however, mean volume of individual LD was greater (P<0.02) in SLC than LLC. In LLC, total LD volume was greater (P<0.02) in O than C and U ewes. In SLC, total LD volume and number was greater (P<0.003) at the mid than early-luteal phase, and percentage of cell volume occupied by LD was greater (P<0.002) in U than C and O ewes. These data demonstrate that both stage of luteal development and nutritional plane affect selected LD measurements and thus may affect luteal functions

  1. Lipid droplets in cultured luteal cells in non-pregnant sheep fed different planes of nutrition.

    PubMed

    Khanthusaeng, Vilaivan; Thammasiri, Jiratti; Bass, Casie S; Navanukraw, Chainarong; Borowicz, Pawel; Redmer, Dale A; Grazul-Bilska, Anna T

    2016-07-01

    Accumulation of lipid droplets (LD) in luteal cells likely is important for energy storage and steroidogenesis in the highly metabolically active corpus luteum (CL). The objective of this study was to determine the effect of plane of nutrition on progesterone (P4) secretion, and lipid droplet number and size in cultured ovine luteal cells. Ewes were randomly assigned to one of three nutritional groups: control (C; 100% NRC requirements, n=9), overfed (O; 2×C, n=12), or underfed (U; 0.6×C, n=10). Superovulation was induced by follicle stimulating hormone injections. At the early and mid-luteal phases of the estrous cycle, CL were dissected from ovaries, and luteal cells isolated enzymatically. Luteal cells were incubated overnight in medium containing serum in chamber slides. Media were then changed to serum-free and after 24h incubation, media were collected for P4 analysis, and cells were fixed in formalin and stained with BODIPY followed by DAPI staining. Z-stacks of optical sections of large and small luteal cells (LLC and SLC, respectively) were obtained using a laser-scanning microscope. Rendered 3D images of individual LLC and SLC were analyzed for cell volume, and total and individual LD volume, number and percentage of cellular volume occupied by LD by using Imaris software. Concentrations of P4 in serum and media were greater (P<0.05) at the mid than early-luteal phase, and were not affected by nutritional plane. LD total volume and number were greater (P<0.001) in LLC than SLC; however, mean volume of individual LD was greater (P<0.02) in SLC than LLC. In LLC, total LD volume was greater (P<0.02) in O than C and U ewes. In SLC, total LD volume and number was greater (P<0.003) at the mid than early-luteal phase, and percentage of cell volume occupied by LD was greater (P<0.002) in U than C and O ewes. These data demonstrate that both stage of luteal development and nutritional plane affect selected LD measurements and thus may affect luteal functions

  2. Dietary factors and luteal phase deficiency in healthy eumenorrheic women

    PubMed Central

    Andrews, Mary A.; Schliep, Karen C.; Wactawski-Wende, Jean; Stanford, Joseph B.; Zarek, Shvetha M.; Radin, Rose G.; Sjaarda, Lindsey A.; Perkins, Neil J.; Kalwerisky, Robyn A.; Hammoud, Ahmad O.; Mumford, Sunni L.

    2015-01-01

    STUDY QUESTION Are prospectively assessed dietary factors, including overall diet quality, macronutrients and micronutrients, associated with luteal phase deficiency (LPD) in healthy reproductive aged women with regular menstrual cycles? SUMMARY ANSWER Mediterranean Diet Score (MDS), fiber and isoflavone intake were positively associated with LPD while selenium was negatively associated with LPD after adjusting for age, percentage body fat and total energy intake. WHAT IS KNOWN ALREADY LPD may increase the risk of infertility and early miscarriage. Prior research has shown positive associations between LPD and low energy availability, either through high dietary restraint alone or in conjunction with high energy expenditure via exercise, but few studies with adequate sample sizes have been conducted investigating dietary factors and LPD among healthy, eumenorrheic women. STUDY DESIGN, SIZE, DURATION The BioCycle Study (2005–2007) prospectively enrolled 259 women from Western New York state, USA, and followed them for one (n = 9) or two (n = 250) menstrual cycles. PARTICIPANTS/MATERIALS, SETTING, METHODS Women aged 18–44 years, with self-reported BMI between 18 and 35 kg/m2 and cycle lengths between 21 and 35 days, were included in the study. Participants completed baseline questionnaires, four 24-h dietary recalls per cycle and daily diaries capturing vigorous exercise, perceived stress and sleep; they also provided up to eight fasting serum samples during clinic visits timed to specific phases of the menstrual cycle using a fertility monitor. Cycles were included for this analysis if the peak serum luteal progesterone was >1 ng/ml and a urine or serum LH surge was detected. Associations between prospectively assessed diet quality, macronutrients and micronutrients and LPD (defined as luteal duration <10 days) were evaluated using generalized linear models adjusting for age, percentage body fat and total energy intake. MAIN RESULTS AND THE ROLE OF CHANCE LPD

  3. Effects of beta-carotene and vitamin A on bovine luteal function

    SciTech Connect

    Graves-Hoagland, R.L.

    1987-01-01

    Initially, the direct effects of B-carotene and vitamin A on progesterone (P4) production were studied by exposing dispersed luteal cells to these compounds in vitro. There were no positive relationships between P4 and B-carotene or vitamin A. However, a negative, and perhaps toxic, effect of a large dose of B-carotene on P4 reproduction was noted. A positive relationship between plasma B-carotene and percent change of P4 in the medium of dispersed luteal cells was demonstrated when these plasma metabolites were measured in slaughterhouse cows from which CL were obtained for incubation. This relationship was only present during the winter when plasma levels of B-carotene and vitamin A were considerably lower. Preliminary investigations into the mechanism of action of B-carotene and/or vitamin A were initiated. Luteal tissue ribonucleic acid (RNA), deoxyribonucleic acid (DNA), the RNA to DNA ratio and total protein concentration were measured to study the influence of plasma levels of B-carotene and vitamin A on the protein synthetic capacity of luteal tissue. There were no relationships detected, however, RNA concentration and the RNA to DNA ratio of luteal tissue were greater during the summer. The percent binding of radiolabeled vitamin A was greater in the nuclear than in the cytoplasmic component of the luteal cell.

  4. Natural and artificial methods for inducing the luteal phase in the koala (Phascolarctos cinereus).

    PubMed

    Johnston, S D; McGowan, M R; O'Callaghan, P; Cox, R; Nicolson, V

    2000-09-01

    An experiment was conducted in which female koalas were mated for different durations of intromission and ejaculation to confirm that the luteal phase of the oestrous cycle in koalas is induced by the physical act of mating. Results showed that induction of a luteal phase in the koala usually required a complete duration of penile thrusting behaviour from the male. It is proposed that induction of a luteal phase in koalas may involve a copuloceptive reflex, triggered by the thrusting of the male's penis into the female's urogenital sinus. Although interrupted mating in koalas may be used to induce a luteal phase in preparation for an artificial insemination programme, this study showed that there is a 12.5% probability that pregnancy will result from semen prematurely emitted by the teaser male. A dose of 250 iu hCG was administered intramuscularly to eight oestrous females to determine whether it was possible to induce a luteal phase artificially. In contrast to control females, which received sterile saline injections, all females injected with hCG showed a significant increase in progestogen concentration above that of basal values, indicating that a luteal phase had been induced successfully. PMID:11006146

  5. A simple and economical method in purifying dairy goat luteal cells.

    PubMed

    Wang, Zhonghui; Chen, Shulin; Mo, Hongfei; Huang, Yingxue; Li, Jinyan; Sun, Jianbo; Liu, Lei; Zhao, Shantin

    2013-08-01

    As an important cell model, luteal cells are used to study the reproductive cycle and pregnancy maintenance, but there has not yet had a simple and economical method in purifing goat luteal cells. In order to find a good method to isolate and purify the luteal cells from the Guan Zhong dairy goat corpus luteua, we compared the purification efficiency of Percoll density gradient centrifugation method with that of the differential detachment method using trypsin. After using these two methods for isolation, the purified cells were identified by staining for 3β-hydroxy steroid dehydrogenase activity. Cell diameter measurements and cell counting were used to categorize isolated cells from both methods. Cell proliferation activity of purified cells from both methods were studied by Cell Counting Kit-8 for 8 days. The results showed that, after Percoll discontinuous density gradient centrifugation, the purity of luteal cells was 98.2±1.2% in Percoll density layer of 30-40%. In comparison, the purity of luteal cells isolated in differential detachment by trypsin was 74.3±1.8%. Luteal cells purified from both methods stained positive for 3β-hydroxy steroid dehydrogenase activity, and cells purified by Percoll centrifugation showed a more rapid cell proliferation rate than cells purified by trypsin. In conclusion, this study has demonstrated that Percoll density gradient centrifugation was superior to the method of differential detachment in cell purification efficiency and in maintenance of cell proliferation activity.

  6. Luteal responses to gonadotropin-releasing hormone during the luteal phase: relation to the age of corpus luteum.

    PubMed

    Caruso, A; Lanzone, A; Fulghesu, A M; Mancuso, S

    1987-02-01

    The pituitary and luteal responsiveness of GnRH were studied in 20 normal women at different stages of the luteal phase (LP). Blood samples were collected every 15 min for 180 min before and 120 min after the iv injection of 25 micrograms GnRH. The studies were performed in the early LP (ELP; days 2-3 of LP; n = 5), mid-LP (MLP: days 4-8 of LP; n = 11), late LP (LLP; days 9-12 of LP; n = 13), and premenstrual phase (PMP; days 13-14 of LP; n = 3). Plasma LH, FSH, progesterone (P), and estradiol (E) levels were assayed by RIA. The data were analyzed as integrated secretory area before (ISAb) and after GnRH stimulation (ISAs) and in terms of their percent increase with respect to the basal value. In all studies, GnRH elicited increases in plasma LH and FSH (P less than 0.001). On the other hand, in the ELP, GnRH did not alter steroid ISAs compared to their ISAb, while significant increases in plasma P and E levels were found in the MLP (P, P less than 0.01; E, P less than 0.02) and LLP (P and E, P less than 0.01). In the PMP, two women had no increase in steroid secretion; in the remainder of the subjects, both P and E ISAs markedly increased. This different pattern was not related to basal steroid levels. All women who had a blunted steroid response in the ELP or PMP had a normal secretory response of both P and E when studied at the other LP stages of the same cycle. Furthermore, there was a positive linear correlation between plasma P and E for the ISAb and ISAs values, while the secretory patterns of gonadotropins and steroids were not related to each other. In conclusion, the corpus luteum is able to respond to GnRH to GnRH at a well identified period of the LP. This pattern indicates variable dependence of the corpus luteum on the functional activity of the hypothalamic-pituitary axis.

  7. Crocin suppresses tumor necrosis factor-alpha-induced cell death of neuronally differentiated PC-12 cells.

    PubMed

    Soeda, S; Ochiai, T; Paopong, L; Tanaka, H; Shoyama, Y; Shimeno, H

    2001-11-01

    Crocus sativus L. is used in Chinese traditional medicine to treat some disorders of the central nervous system. Crocin is an ethanol-extractable component of Crocus sativus L.; it is reported to prevent ethanol-induced impairment of learning and memory in mice. In this study, we demonstrate that crocin suppresses the effect of tumor necrosis factor (TNF)-alpha on neuronally differentiated PC-12 cells. PC-12 cells dead from exposure to TNF-alpha show apoptotic morphological changes and DNA fragmentation. These hallmark features of cell death did not appear in cells treated in the co-presence of 10 microM crocin. Moreover, crocin suppressed the TNF-alpha-induced expression of Bcl-Xs and LICE mRNAs and simultaneously restored the cytokine-induced reduction of Bcl-X(L) mRNA expression. The modulating effects of crocin on the expression of Bcl-2 family proteins led to a marked reduction of a TNF-alpha-induced release of cytochrome c from the mitochondria. Crocin also blocked the cytochrome c-induced activation of caspase-3. To learn how crocin exhibits these anti-apoptotic actions in PC-12 cells, we tested the effect of crocin on PC-12 cell death induced by daunorubicin. We found that crocin inhibited the effect of daunorubicin as well. Our findings suggest that crocin inhibits neuronal cell death induced by both internal and external apoptotic stimuli.

  8. The {alpha}-induced thick-target {gamma}-ray yield from light elements

    SciTech Connect

    Heaton, R.K. |

    1994-10-01

    The {alpha}-induced thick-target {gamma}-ray yield from light elements has been measured in the energy range 5.6 MeV {le} E{sub {alpha}} {le} 10 MeV. The {gamma}-ray yield for > 2.1 MeV from thick targets of beryllium, boron nitride, sodium fluoride, magnesium, aluminum and silicon were measured using the {alpha}-particle beam from the Lawrence Berkeley Laboratories 88 in. cyclotron. The elemental yields from this experiment were used to construct the {alpha}-induced direct production {gamma}-ray spectrum from materials in the SNO detector, a large volume ultra-low background neutrino detector located in the Creighton mine near Sudbury, Canada. This background source was an order of magnitude lower than predicted by previous calculations. These measurements are in good agreement with theoretical calculations of this spectrum based on a statistical nuclear model of the reaction, with the gross high energy spectrum structure being reproduced to within a factor of two. Detailed comparison of experimental and theoretical excitation population distribution of several residual nuclei indicate the same level of agreement within experimental uncertainties.

  9. The HPV-16 E7 oncogene sensitizes malignant cells to IFN-alpha-induced apoptosis

    SciTech Connect

    Wang, Yisong

    2005-10-01

    Interferons (IFNs) exert antitumor effects in several human malignancies, but their mechanism of action is unclear. There is a great variability in sensitivity to IFN treatment depending on both tumor type and the individual patient. The reason for this variable sensitivity is not known. The fact that several IFN-induced anticellular effects are exerted through modulation of proto-oncogenes and tumor suppressor genes may indicate that the malignant genotype may be decisive in the cell's sensitivity to IFN. To determine if a deregulated oncogene could alter the cellular response to IFN, a mouse lymphoma cell line (J3D) was stably transfected with the viral human papillomavirus-16 (HPV-16) E7 oncogene. The E7-transfected cells and their respective mock-transfected sister clones were treated with IFN-{alpha} and examined for possible IFN-induced anticellular effects. We found that the E7-transfected clones were greatly sensitized to IFN-{alpha}-induced apoptosis compared with their mock-transfected counterparts. Induction of apoptosis in the transfected cells correlated with the ability of IFN to activate parts of the proapoptotic machinery specifically in these cells, including activation of caspases and the proapoptotic protein Bak. In summary, our data suggest that transfection of malignant cells with the E7 oncogene can sensitize them to IFN-{alpha}-induced apoptosis. This demonstrates that an oncogenic event may alter the cellular sensitivity to IFN and might also have implications for treatment of HPV related diseases with IFN.

  10. Eicosapentaenoic acid inhibits TNF-{alpha}-induced matrix metalloproteinase-9 expression in human keratinocytes, HaCaT cells

    SciTech Connect

    Kim, Hyeon Ho; Lee, Youngae; Eun, Hee Chul Chung, Jin Ho

    2008-04-04

    Eicosapentaenoic acid (EPA) is an omega-3 ({omega}-3) polyunsaturated fatty acid (PUFA), which has anti-inflammatory and anti-cancer properties. Some reports have demonstrated that EPA inhibits NF-{kappa}B activation induced by tumor necrosis factor (TNF)-{alpha} or lipopolysaccharide (LPS) in various cells. However, its detailed mode of action is unclear. In this report, we investigated whether EPA inhibits the expression of TNF-{alpha}-induced matrix metalloproteinases (MMP)-9 in human immortalized keratinocytes (HaCaT). TNF-{alpha} induced MMP-9 expression by NF-{kappa}B-dependent pathway. Pretreatment of EPA inhibited TNF-{alpha}-induced MMP-9 expression and p65 phosphorylation. However, EPA could not affect I{kappa}B-{alpha} phosphorylation, nuclear translocation of p65, and DNA binding activity of NF-{kappa}B. EPA inhibited TNF-{alpha}-induced p65 phosphorylation through p38 and Akt inhibition and this inhibition was IKK{alpha}-dependent event. Taken together, we demonstrate that EPA inhibits TNF-{alpha}-induced MMP-9 expression through inhibition of p38 and Akt activation.

  11. Semen-induced luteal phase and identification of a LH surge in the koala (Phascolarctos cinereus).

    PubMed

    Johnston, S D; O'Callaghan, P; Nilsson, K; Tzipori, G; Curlewis, J D

    2004-11-01

    The koala ovulates in response to mating. The purpose of this study was to document the LH surge induced by copulation and to investigate the potential roles of mechanical stimulation of the urogenital sinus and deposition of semen in induction of the luteal phase. In experiment 1, serial blood samples from four koalas that underwent normal mating showed elevated concentrations of LH approximately 24-32 h post-coitus. There was no corresponding elevation in LH in koalas (n=4) that were exposed to the presence of a male but received no physical contact. In experiment 2, koalas on day 2 of oestrus were exposed to one of the following treatments (n=9 per group): artificial insemination with 1 ml 0.9% sterile saline (control group), insemination with 1 ml koala semen, stimulation of the urogenital sinus with a purpose built glass rod (designed to mimic the action of the penis during natural mating) and urogenital stimulation with the glass rod followed by insemination of 1 ml koala semen. Confirmation of a luteal phase was based on evidence of a prolonged return to oestrus, parturition and/or elevated progesterone concentrations. Insemination of saline (0/9) and urogenital stimulation (0/9) failed to induce a luteal phase. Insemination of semen without glass rod stimulation resulted in a luteal phase in 4/9 koalas, three of which gave birth. Insemination of semen in combination with urogenital stimulation produced a luteal phase in 7/9 koalas, four of which gave birth. Semen had a significant effect on induction of the koala luteal phase (P <0.001) but glass rod stimulation had no such effect (P=0.335). It was concluded that semen must be involved in the induction of a luteal phase in the koala. The results presented in this study will serve to improve optimal timing and induction of ovulation for artificial insemination in the koala. PMID:15509709

  12. The coffee diterpene kahweol inhibits tumor necrosis factor-{alpha}-induced expression of cell adhesion molecules in human endothelial cells

    SciTech Connect

    Kim, Hyung Gyun; Kim, Ji Young; Hwang, Yong Pil; Lee, Kyung Jin; Lee, Kwang Youl; Kim, Dong Hee; Kim, Dong Hyun; Jeong, Hye Gwang . E-mail: hgjeong@chosun.ac.kr

    2006-12-15

    Endothelial cells produce adhesion molecules after being stimulated with various inflammatory cytokines. These adhesion molecules play an important role in the development of atherogenesis. Recent studies have highlighted the chemoprotective and anti-inflammatory effects of kahweol, a coffee-specific diterpene. This study examined the effects of kahweol on the cytokine-induced monocyte/human endothelial cell interaction, which is a crucial early event in atherogenesis. Kahweol inhibited the adhesion of TNF{alpha}-induced monocytes to endothelial cells and suppressed the TNF{alpha}-induced protein and mRNA expression of the cell adhesion molecules, VCAM-1 and ICAM-1. Furthermore, kahweol inhibited the TNF{alpha}-induced JAK2-PI3K/Akt-NF-{kappa}B activation pathway in these cells. Overall, kahweol has anti-inflammatory and anti-atherosclerotic activities, which occurs partly by down-regulating the pathway that affects the expression and interaction of the cell adhesion molecules on endothelial cells.

  13. Expression of steroidogenic acute regulatory protein in the human corpus luteum throughout the luteal phase.

    PubMed

    Devoto, L; Kohen, P; Gonzalez, R R; Castro, O; Retamales, I; Vega, M; Carvallo, P; Christenson, L K; Strauss, J F

    2001-11-01

    The expression of the steroidogenic acute regulatory protein (StAR) in the human corpus luteum (CL) was examined throughout the luteal phase. The primary 1.6-kb StAR transcript was in greater abundance in early (3.1-fold) and mid (2.2-fold) luteal phase CL compared with late luteal phase CL. The larger StAR transcript (4.4 kb) was found in early and midluteal phase CL, but was not detected in late luteal phase specimens. Mature StAR protein (30 kDa) was present in lower amounts within late CL compared with early and midluteal phase CL. The StAR preprotein (37 kDa) was also detected in greater abundance in early and midluteal CL. Immunohistochemistry revealed that StAR staining was most prominent in thecal-lutein cells throughout the luteal phase. The intensity of the signal for StAR exhibited significant changes throughout the luteal phase, being most intense during the midluteal phase and least during the late luteal phase. Plasma progesterone concentrations were highly correlated (r = 0.73 and r = 0.79) with luteal expression of the preprotein and mature StAR isoforms, respectively, throughout the luteal phase. To examine the LH dependency of StAR expression, the GnRH antagonist, Cetrorelix, was administered during the midluteal phase. Cetrorelix caused a decline in serum LH levels within 2 h, which, in turn, caused a pronounced decline in plasma progesterone within 6 h. The StAR 4.4-kb transcript was not detectable, and the 1.6-kb transcript was reduced by approximately 50% within 24 h of Cetrorelix treatment. The mature 30-kDa StAR protein level declined approximately 30% after Cetrorelix treatment. We conclude that 1) StAR mRNA and protein are highly expressed in early and midluteal phase CL; 2) StAR protein is present in both thecal-lutein and granulosa-lutein cells throughout the luteal phase; 3) StAR protein levels in the CL are highly correlated with plasma progesterone levels; 4) declining StAR mRNA and protein levels are characteristic of late luteal

  14. Effect of luteal-phase support on endometrial microRNA expression following controlled ovarian stimulation

    PubMed Central

    2012-01-01

    Background Studies suggested that microRNAs influence cellular activities in the uterus including cell differentiation and embryo implantation. In assisted reproduction cycles, luteal phase support, given to improve endometrial characteristics and to facilitate the implantation process, has been a standard practice. The effect of different types of luteal phase support using steroid hormones in relation to endometrial miRNA profiles during the peri-implantation period has not seen described. This study was designed to evaluate the expression of miRNAs during the luteal phase following controlled ovarian stimulation for IVF and the influence of different luteal phase support protocols on miRNA profiles. Methods The study was approved by the Johns Hopkins Hospital Institutional Review Board. Endometrial biopsies were obtained on the day of oocyte retrieval from 9 oocyte donors (group I). An additional endometrial biopsy was obtained 3–5 days later (Group II) after the donors were randomized into three groups. Group IIa had no luteal-phase support, group IIb had luteal support with micronized progesterone (P), and Group IIc had luteal support with progesterone plus 17-beta-estradiol (P + E). Total RNA was isolated and microarray analysis was performed using an Illumina miRNA expression panel. Results A total of 526 miRNAs were identified. Out of those, 216 miRNAs were differentially regulated (p < 0.05) between the comparison groups. As compared to the day of retrieval, 19, 11 and 6 miRNAs were differentially regulated more than 2 fold in the groups of no support, in the P support only, and in the P + E support respectively, 3–5 days after retrieval. During the peri-implantation period (3–5 days after retrieval) the expression of 33 and 6 miRNAs increased, while the expression of 3 and 0 miRNAs decreased, in the P alone and in the P + E group respectively as compared to the no steroid supplementation group. Conclusion Luteal support

  15. Clinostat rotation induces apoptosis in luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Yang, Hyunwon; Bhat, Ganapathy K.; Sridaran, Rajagopala

    2002-01-01

    Recent studies have shown that microgravity induces changes at the cellular level, including apoptosis. However, it is unknown whether microgravity affects luteal cell function. This study was performed to assess whether microgravity conditions generated by clinostat rotation induce apoptosis and affect steroidogenesis by luteal cells. Luteal cells isolated from the corpora lutea of Day 8 pregnant rats were placed in equal numbers in slide flasks (chamber slides). One slide flask was placed in the clinostat and the other served as a stationary control. At 48 h in the clinostat, whereas the levels of progesterone and total cellular protein decreased, the number of shrunken cells increased. To determine whether apoptosis occurred in shrunken cells, Comet and TUNEL assays were performed. At 48 h, the percentage of apoptotic cells in the clinostat increased compared with that in the control. To investigate how the microgravity conditions induce apoptosis, the active mitochondria in luteal cells were detected with JC-1 dye. Cells in the control consisted of many active mitochondria, which were evenly distributed throughout the cell. In contrast, cells in the clinostat displayed fewer active mitochondria, which were distributed either to the outer edge of the cell or around the nucleus. These results suggest that mitochondrial dysfunction induced by clinostat rotation could lead to apoptosis in luteal cells and suppression of progesterone production.

  16. Nicotine Pretreatment Increases Dysphoric Effects of Alcohol in Luteal-Phase Female Volunteers

    PubMed Central

    Penetar, David M.; Kouri, Elena M.; McCarthy, Elissa M.; Lilly, Michelle M.; Peters, Erica N.; Juliano, Trisha M.; Lukas, Scott E.

    2009-01-01

    The present report shows that nicotine enhances some of alcohol’s positive and negative effects in women and that these effects are most pronounced during the luteal phase of the menstrual cycle. Ten low progesterone and 10 high progesterone/luteal-phase women received nicotine patch pretreatments (placebo or 21 mg) 3 hours before an alcohol challenge (0.4 g/kg). Subjective effects were recorded on mood adjective scales and the Addiction Research Center Inventory (ARCI). Heart rate and skin temperature were recorded. Luteal-phase women reported peak positive (e.g. “stimulated”) and peak negative effects (e.g. “clumsy”, “dizzy”) almost twice as great as low progesterone women. PMID:19440397

  17. Subcutaneous Progesterone Is Effective and Safe for Luteal Phase Support in IVF: An Individual Patient Data Meta-Analysis of the Phase III Trials

    PubMed Central

    Doblinger, Jakob; Cometti, Barbara; Trevisan, Silvia; Griesinger, Georg

    2016-01-01

    Objective To summarize efficacy and safety data on a new progesterone compound which is available for subcutaneous administration as compared to vaginally administered progesterone for luteal phase support in patients undergoing IVF treatment. Design Data from two randomized phase III trials (07EU/Prg06 and 07USA/Prg05) performed according to GCP standards with a total sample size of 1435 per-protocol patients were meta-analyzed on an individual patient data level. Setting University affiliated reproductive medicine unit. Patients Subcutaneous progesterone was administered to a total of 714 subjects and vaginal progesterone was administered to a total of 721 subjects who underwent fresh embryo transfer after ovarian stimulation followed by IVF or ICSI. The subjects were between 18 and 42 years old and had a BMI <30kg/m2. Interventions Subcutaneous progesterone 25 mg daily vs. either progesterone vaginal gel 90 mg daily (07EU/Prg06) or 100 mg intravaginal twice a day (07USA/Prg05) for luteal phase support in IVF patients. Main outcome measures Ongoing pregnancy rate beyond 10 gestational weeks, live birth rate and OHSS risk. Results The administration of subcutaneous progesterone versus intra-vaginal progesterone had no impact on ongoing pregnancy likelihood (OR = 0.865, 95% CI 0.694 to 1.077; P = n.s.), live birth likelihood (OR = 0.889, 95% CI 0.714 to 1.106; P = n.s.) or OHSS risk (OR = 0.995, 95% CI 0.565 to 1.754; P = n.s.) in regression analyses accounting for clustering of patients within trials, while adjusting for important confounders. Only female age and number of oocytes retrieved were significant predictors of live birth likelihood and OHSS risk. Conclusion No statistical significant or clinical significant differences exist between subcutaneous and vaginal progesterone for luteal phase support. PMID:26991890

  18. Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules.

    PubMed

    Ibrahim, Laila A; Kramer, Joseph M; Williams, R Stan; Bromfield, John J

    2016-10-01

    The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response.

  19. Human granulosa-luteal cells initiate an innate immune response to pathogen-associated molecules.

    PubMed

    Ibrahim, Laila A; Kramer, Joseph M; Williams, R Stan; Bromfield, John J

    2016-10-01

    The microenvironment of the ovarian follicle is key to the developmental success of the oocyte. Minor changes within the follicular microenvironment can significantly disrupt oocyte development, compromising the formation of competent embryos and reducing fertility. Previously described as a sterile environment, the ovarian follicle of women has been shown to contain colonizing bacterial strains, whereas in domestic species, pathogen-associated molecules are concentrated in the follicular fluid of animals with uterine infection. The aim of this study is to determine whether human granulosa-luteal cells mount an innate immune response to pathogen-associated molecules, potentially disrupting the microenvironment of the ovarian follicle. Human granulosa-luteal cells were collected from patients undergoing assisted reproduction. Cells were cultured in the presence of pathogen-associated molecules (LPS, FSL-1 and Pam3CSK4) for 24h. Supernatants and total RNA were collected for assessment by PCR and ELISA. Granulosa-luteal cells were shown to express the molecular machinery required to respond to a range of pathogen-associated molecules. Expression of TLR4 varied up to 15-fold between individual patients. Granulosa-luteal cells increased the expression of the inflammatory mediators IL1B, IL6 and CXCL8 in the presence of the TLR4 agonist E. coli LPS. Similarly, the TLR2/6 ligand, FSL-1, increased the expression of IL6 and CXCL8. Although no detectable changes in CYP19A1 or STAR expression were observed in granulosa-luteal cells following challenge, a significant reduction in progesterone secretion was measured after treatment with FSL-1. These findings demonstrate the ability of human granulosa-luteal cells to respond to pathogen-associated molecules and generate an innate immune response. PMID:27512120

  20. Colour Doppler Ultrasonography as a Tool to Assess Luteal Function in Santa Inês Ewes.

    PubMed

    Figueira, L M; Fonseca, J F; Arashiro, Ekn; Souza-Fabjan, Jmg; Ribeiro, Acs; Oba, E; Viana, Jhm; Brandão, F Z

    2015-08-01

    The aim of this study was to evaluate luteal dynamics in the Santa Inês ewes using colour Doppler (CD) ultrasonography. Oestrus was synchronized in nulliparous females (n = 18), and subsequently, they were only teased (n = 6) or teased and mated (n = 12). Blood samples were collected daily for plasma progesterone (P4 ) concentrations. Ultrasonographic images of corpora lutea (CL) in CD mode were obtained for further analysis in its largest diameter. The CD mode allowed an early sequential monitoring of CL that was visualized by the first time 0.77 ± 0.62 days after ovulation, with luteal area 29.68 ± 13.21 mm(2) . During the luteogenesis, a progressive increase was observed, followed by a plateau of luteal area, vascularization area and plasma concentrations of P4 reaching maximum values in D11 (124.0 ± 38.0 mm(2) , 52.78 ± 24.08 mm(2) and 11.23 ± 4.89 ng/ml, respectively). In the luteolysis, the plasma concentrations of P4 decreased sharply, whereas luteal and vascularization area gradually. The vascularization area was positively correlated with plasma concentrations of P4 during the luteogenesis (r = 0.22) and luteolysis (r = 0.48). The luteal dynamics of Santa Inês ewes showed patterns similar to those observed in other sheep breeds studied. The CD ultrasonography has the potential to be used as a tool to assess luteal function in sheep.

  1. Autistic Regression

    ERIC Educational Resources Information Center

    Matson, Johnny L.; Kozlowski, Alison M.

    2010-01-01

    Autistic regression is one of the many mysteries in the developmental course of autism and pervasive developmental disorders not otherwise specified (PDD-NOS). Various definitions of this phenomenon have been used, further clouding the study of the topic. Despite this problem, some efforts at establishing prevalence have been made. The purpose of…

  2. EFFECTS OF BROMODICHLOROMETHANE (BDCM) ON EX VIVO LUTEAL FUNCTION IN THE F344 RAT DURING PREGNANCY

    EPA Science Inventory

    Effects of Bromodichloromethane (BDCM) on Ex Vivo Luteal Function In the Pregnant F344 Rat

    Susan R. Bielmeier1, Ashley S. Murr2, Deborah S. Best2, Jerome M. Goldman2, and Michael G. Narotsky2

    1Curriculum in Toxicology, Univ. of North Carolina, Chapel Hill, NC 27599,...

  3. Effects of concanavalin A on the progesterone production by bovine steroidogenic luteal cells in vitro.

    PubMed

    Destro, F C; Martin, I; Landim-Alvarenga, Fdc; Ferreira, Jcp; Pate, J L

    2016-10-01

    The aim of this study was to evaluate the effects of concanavalin A (CONA) on the progesterone (P4) production by bovine steroidogenic luteal cells (LCs) in vitro. Luteal cells were collected during the mid-luteal stage (at 10-12 days following ovulation) and processed in the laboratory. Luteal cells were grown for 7 days in a humid atmosphere with 5% CO2 , with or without 10% foetal bovine serum, and were subjected to the following treatments: control: no treatment; CONA (10 μg/ml); LH (100 μg/ml); CONA + LH; LH (100 μg/ml) + prostaglandin F2α (PGF2α) (10 ng/ml); CONA + LH + PGF2α. Samples of the culture media were collected on days 1 (D1) and 7 (D7) for P4 quantification. The cells were counted on D7 of culture. Differences between treatments were considered statistically significant at p < .05. Culture in the presence of CONA decreased the P4-secreting capacity of LCs on D7 of culture, particularly in the absence of serum. The cell numbers did not change between treatments.

  4. Natural Micronized Progesterone Sustained Release (SR) and Luteal Phase: Role Redefined!!

    PubMed Central

    Malik, Sonia

    2016-01-01

    Role of progesterone in reproductive medicine is evolving with its suggested clinical role for the hormonal and nonhormonal actions in reproductive medicine. The main function of progesterone is to induce ‘secretory’ changes in endometrium that is further complimented by its immunomodulatory and anti-inflammatory actions. It positively modulates PIBF, NK cells and HOXA 10 genes for better implantation. MHRA recommends Serum Progesterone levels ≥14ng/ml in the mid-luteal phase for supporting pregnancy adequately. Oral Natural Micronized Progesterone SR formulation represents a therapeutic advance in this direction offering ‘therapeutic compliance’ with oral formulation while avoiding the local side effects related to long-term patient compliance in reproductive disorders. The formulation offers round the clock efficiency and efficacy with single dose administration thereby improving patient convenience and compliance. This formulation has been marketed globally since 1986 utilizing the well validated drug delivery system involving Methylcellulose base. The clinical utility of this formulation is further suggested especially in various conditions related with luteal phase insufficiency and Bad obstetric history (BOH) or luteal phase support in ART. The level of evidence has been quite robust with several clinical studies including Prescription Event Monitoring and Investigator initiated studies supporting the clinical role of oral NMP SR formulation especially in ‘Real world’ clinic settings for Luteal phase insufficiency that may be physiological or iatrogenic. PMID:27042538

  5. Effects of concanavalin A on the progesterone production by bovine steroidogenic luteal cells in vitro.

    PubMed

    Destro, F C; Martin, I; Landim-Alvarenga, Fdc; Ferreira, Jcp; Pate, J L

    2016-10-01

    The aim of this study was to evaluate the effects of concanavalin A (CONA) on the progesterone (P4) production by bovine steroidogenic luteal cells (LCs) in vitro. Luteal cells were collected during the mid-luteal stage (at 10-12 days following ovulation) and processed in the laboratory. Luteal cells were grown for 7 days in a humid atmosphere with 5% CO2 , with or without 10% foetal bovine serum, and were subjected to the following treatments: control: no treatment; CONA (10 μg/ml); LH (100 μg/ml); CONA + LH; LH (100 μg/ml) + prostaglandin F2α (PGF2α) (10 ng/ml); CONA + LH + PGF2α. Samples of the culture media were collected on days 1 (D1) and 7 (D7) for P4 quantification. The cells were counted on D7 of culture. Differences between treatments were considered statistically significant at p < .05. Culture in the presence of CONA decreased the P4-secreting capacity of LCs on D7 of culture, particularly in the absence of serum. The cell numbers did not change between treatments. PMID:27558864

  6. Gene expression profiling bovine ovarian follicular and luteal cells provides insight into cellular identities and functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  7. Robust Regression.

    PubMed

    Huang, Dong; Cabral, Ricardo; De la Torre, Fernando

    2016-02-01

    Discriminative methods (e.g., kernel regression, SVM) have been extensively used to solve problems such as object recognition, image alignment and pose estimation from images. These methods typically map image features ( X) to continuous (e.g., pose) or discrete (e.g., object category) values. A major drawback of existing discriminative methods is that samples are directly projected onto a subspace and hence fail to account for outliers common in realistic training sets due to occlusion, specular reflections or noise. It is important to notice that existing discriminative approaches assume the input variables X to be noise free. Thus, discriminative methods experience significant performance degradation when gross outliers are present. Despite its obvious importance, the problem of robust discriminative learning has been relatively unexplored in computer vision. This paper develops the theory of robust regression (RR) and presents an effective convex approach that uses recent advances on rank minimization. The framework applies to a variety of problems in computer vision including robust linear discriminant analysis, regression with missing data, and multi-label classification. Several synthetic and real examples with applications to head pose estimation from images, image and video classification and facial attribute classification with missing data are used to illustrate the benefits of RR. PMID:26761740

  8. Interferon alpha-inducible protein 6 regulates NRASQ61K-induced melanomagenesis and growth

    PubMed Central

    Gupta, Romi; Forloni, Matteo; Bisserier, Malik; Dogra, Shaillay Kumar; Yang, Qiaohong; Wajapeyee, Narendra

    2016-01-01

    Mutations in the NRAS oncogene are present in up to 20% of melanoma. Here, we show that interferon alpha-inducible protein 6 (IFI6) is necessary for NRASQ61K-induced transformation and melanoma growth. IFI6 was transcriptionally upregulated by NRASQ61K, and knockdown of IFI6 resulted in DNA replication stress due to dysregulated DNA replication via E2F2. This stress consequentially inhibited cellular transformation and melanoma growth via senescence or apoptosis induction depending on the RB and p53 pathway status of the cells. NRAS-mutant melanoma were significantly more resistant to the cytotoxic effects of DNA replication stress-inducing drugs, and knockdown of IFI6 increased sensitivity to these drugs. Pharmacological inhibition of IFI6 expression by the MEK inhibitor trametinib, when combined with DNA replication stress-inducing drugs, blocked NRAS-mutant melanoma growth. Collectively, we demonstrate that IFI6, via E2F2 regulates DNA replication and melanoma development and growth, and this pathway can be pharmacologically targeted to inhibit NRAS-mutant melanoma. DOI: http://dx.doi.org/10.7554/eLife.16432.001 PMID:27608486

  9. Tat-APE1/ref-1 protein inhibits TNF-alpha-induced endothelial cell activation.

    PubMed

    Song, Yun Jeong; Lee, Ji Young; Joo, Hee Kyoung; Kim, Hyo Shin; Lee, Sang Ki; Lee, Kwon Ho; Cho, Chung-Hyun; Park, Jin Bong; Jeon, Byeong Hwa

    2008-03-28

    Apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/ref-1) is a multifunctional protein involved both in DNA base excision repair and redox regulation. In this study we evaluated the protective role of Tat-mediated APE1/ref-1 transduction on the tumor necrosis factor (TNF)-alpha-activated endothelial activation in cultured human umbilical vein endothelial cells. To construct Tat-APE1/ref-1 fusion protein, human full length of APE1/ref-1 was fused with Tat-protein transduction domain. Purified Tat-APE1/ref-1 fusion protein efficiently transduced cultured endothelial cells in a dose-dependent manner and reached maximum expression at 1h after incubation. Transduced Tat-APE1/ref-1 showed inhibitory activity on the TNF-alpha-induced monocyte adhesion and vascular cell adhesion molecule-1 expression in cultured endothelial cells. These results suggest Tat-APE1/ref-1 might be useful to reduce vascular endothelial activation or vascular inflammatory disorders.

  10. DNA-binding activity of TNF-{alpha} inducing protein from Helicobacter pylori

    SciTech Connect

    Kuzuhara, T. Suganuma, M.; Oka, K.; Fujiki, H.

    2007-11-03

    Tumor necrosis factor-{alpha} (TNF-{alpha}) inducing protein (Tip{alpha}) is a carcinogenic factor secreted from Helicobacter pylori (H. pylori), mediated through both enhanced expression of TNF-{alpha} and chemokine genes and activation of nuclear factor-{kappa}B. Since Tip{alpha} enters gastric cancer cells, the Tip{alpha} binding molecules in the cells should be investigated. The direct DNA-binding activity of Tip{alpha} was observed by pull down assay using single- and double-stranded genomic DNA cellulose. The surface plasmon resonance assay, indicating an association between Tip{alpha} and DNA, revealed that the affinity of Tip{alpha} for (dGdC)10 is 2400 times stronger than that of del-Tip{alpha}, an inactive Tip{alpha}. This suggests a strong correlation between DNA-binding activity and carcinogenic activity of Tip{alpha}. And the DNA-binding activity of Tip{alpha} was first demonstrated with a molecule secreted from H. pylori.

  11. Tumor necrosis factor alpha-induced angiogenesis depends on in situ platelet-activating factor biosynthesis

    PubMed Central

    1994-01-01

    Tumor necrosis factor (TNF) alpha, a potent inhibitor of endothelial cell growth in vitro, is angiogenic in vivo. Therefore, it was suggested that the angiogenic properties of this agent might be consequent to the production of secondary mediators. Since TNF-alpha stimulates the synthesis of platelet-activating factor (PAF) by monocytes and endothelial cells, we investigated the possible involvement of PAF in the angiogenic effect of TNF-alpha. Angiogenesis was studied in a murine model in which Matrigel was used as a vehicle for the delivery of mediators. In this model the angiogenesis induced by TNF-alpha was shown to be inhibited by WEB 2170, a specific PAF receptor antagonist. Moreover, in mice injected with TNF-alpha, PAF was detected within the Matrigel, 6 and 24 h after TNF-alpha injection. The synthesis of PAF within the Matrigel was concomitant with the early migration of endothelial cells and infiltration of monocytes. No infiltration of lymphocytes or polymorphonuclear leukocytes was observed. Synthetic PAF as well as PAF extracted and purified from mice challenged with TNF-alpha induced a rapid angiogenic response, inhibited by WEB 2170. These results suggest that the angiogenic effect of TNF-alpha is, at least in part, mediated by PAF synthesized from monocytes and/or endothelial cells infiltrating the Matrigel plug. PMID:7516414

  12. Comparison of oral dydrogesterone with vaginal progesteronefor luteal support in IUI cycles: a randomized clinical trial

    PubMed Central

    Khosravi, Donya; Taheripanah, Robabeh; Taheripanah, Anahita; Tarighat Monfared, Vahid; Hosseini-Zijoud, Seyed-Mostafa

    2015-01-01

    Background: The aim of this study, we have compared the advantages of oral dydrogestrone with vaginal progesterone (cyclogest) for luteal support in intrauterine insemination (IUI) cycles. Progesterone supplementation is the first line treatment when luteal phase deficiency (LPD) can reasonably be assumed. Objective: This study was conduct to compare the effect of oral dydrogestrone with vaginal Cyclogest on luteal phase support in the IUI cycles. Materials and Methods: This prospective, randomized, double blind study was performed in a local infertility center from May 2013 to May 2014. It consisted of 150 infertile women younger than35years old undergoing ovarian stimulation for IUI cycles. They underwent ovarian stimulation with oral dydrogesterone (20 mg) as group A and vaginal cyclogest (400 mg) as group B in preparation for the IUI cycles. Clinical pregnancy and abortion rates, mid luteal progesterone (7daysafter IUI) and patient satisfaction were compared between two groups. Results: The mean serum progesterone levels was significantly higher in group A in comparison with group B (p=0.001). Pregnancy rates in group A was not statistically different in comparison with group B (p =0.58). Abortion rate in two groups was not statistically different (p =0.056) although rate of abortion was higher in group B in comparison with A group. Satisfaction rates were significantly higher in group A compared to group B (p<0.001). Conclusion: We concluded that oral dydrogestrone is effective as vaginal progesterone for luteal-phase support in woman undergoing IUI cycles. Moreover, the mean serum progesterone levels and satisfaction rates in dydrogestrone group were higher than cyclogest group. PMID:26494991

  13. NBBA, a synthetic small molecule, inhibits TNF-{alpha}-induced angiogenesis by suppressing the NF-{kappa}B signaling pathway

    SciTech Connect

    Kim, Nam Hee; Jung, Hye Jin; Shibasaki, Futoshi; Kwon, Ho Jeong

    2010-01-15

    Nuclear factor-{kappa}B (NF-{kappa}B) is a crucial transcription factor that contributes to cancer development by regulating a number of genes involved in angiogenesis and tumorigenesis. Here, we describe (Z)-N-(3-(7-nitro-3-oxobenzo[d][1,2]selenazol-2(3H)-yl)benzylidene) propan-2-amine oxide (NBBA) as a new anti-angiogenic small molecule that targets NF-{kappa}B activity. NBBA showed stronger growth inhibition on human umbilical vein endothelial cells (HUVECs) than on the cancer cell lines we tested. Moreover, NBBA inhibited tumor necrosis factor-alpha (TNF-{alpha})-induced tube formation and invasion of HUVECs. In addition, NBBA suppressed the neovascularization of chorioallantonic membrane from growing chick embryos in vivo. To address the mode of action of the compound, the effect of NBBA on TNF-{alpha}-induced NF-{kappa}B transcription activity was investigated. NBBA suppressed TNF-{alpha}-induced c-Jun N-terminal kinase phosphorylation, which resulted in suppression of transcription of NF-{kappa}B and its target genes, including interleukin-8, interleukin-1{alpha}, and epidermal growth factor. Collectively, these results demonstrated that NBBA is a new anti-angiogenic small molecule that targets the NF-{kappa}B signaling pathway.

  14. Calcitriol inhibits TNF-alpha-induced inflammatory cytokines in human trophoblasts.

    PubMed

    Díaz, Lorenza; Noyola-Martínez, Nancy; Barrera, David; Hernández, Guillermo; Avila, Euclides; Halhali, Ali; Larrea, Fernando

    2009-07-01

    Elevated placental proinflammatory cytokine release is associated with miscarriage, preterm labor and preeclampsia. Specifically, tumor necrosis factor-alpha (TNF-alpha)-induced cytokines may threaten pregnancy outcome. Since trophoblasts produce calcitriol, a hormone with strong immunosuppressive properties, we assessed the effects of this secosteroid on inflammatory cytokines induced in trophoblasts by challenge with TNF-alpha. The effects of calcitriol on synthesis of mRNAs encoding interleukin-6 (IL-6), interferon-gamma (IFN-gamma), and TNF-alpha were measured by real time RT-PCR. Secreted cytokines were quantified by ELISA. The effects of TNF-alpha on CYP24A1, chorionic gonadotropin (hCG), 3beta-hydroxysteroid dehydrogenase (HSD3B1) and P(450)-aromatase (CYP19) mRNA expression were also studied. TNF-alpha stimulated IL-6, IFN-gamma and its own expression more than 3-fold over controls (P<0.05). Calcitriol inhibited the expression profile of inflammatory cytokine genes in a dose-response manner (P<0.05). This effect was prevented by addition of the vitamin D receptor antagonist TEI-9647. TNF-alpha also significantly inhibited expression of hCG, HSD3B1 and CYP19 genes, and stimulated CYP24A1 gene expression. These data show that calcitriol prevents TNF-alpha induction of inflammatory cytokines through a process likely to be mediated by the vitamin D receptor. We conclude that TNF-alpha inhibits placental hormone synthesis and stimulates calcitriol catabolism by regulating enzymes involved in these processes.

  15. Influence of Reproductive Aging of the Cow on Luteal Function and Period 1 mRNA Expression

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In rodents, disruption of the circadian clock genes results in increased incidence of anovulation, irregular estrous cycles, decreased luteal function, and accelerated reproductive ageing. In cattle, reproductive ageing is associated with decreased numbers of follicles in the ovary, decreased lutea...

  16. Systemic and renal hemodynamic changes in the luteal phase of the menstrual cycle mimic early pregnancy.

    PubMed

    Chapman, A B; Zamudio, S; Woodmansee, W; Merouani, A; Osorio, F; Johnson, A; Moore, L G; Dahms, T; Coffin, C; Abraham, W T; Schrier, R W

    1997-11-01

    Blood pressure decreases during early pregnancy in association with a decrease in peripheral vascular resistance and increases in renal plasma flow and glomerular filtration rate. These early changes suggest a potential association with corpora lutea function. To determine whether peripheral vasodilation occurs following ovulation, we studied 16 healthy women in the midfollicular and midluteal phases of the menstrual cycle. A significant decrease in mean arterial pressure in the midluteal phase of the cycle (midfollicular of 81.7 +/- 2.0 vs. midluteal of 75.4 +/- 2.3 mmHg, P < 0.005) was found in association with a decrease in systemic vascular resistance and an increase in cardiac output. Renal plasma flow and glomerular filtration rate increased. Plasma renin activity and aldosterone concentration increased significantly in the luteal phase accompanied by a decrease in atrial natriuretic peptide concentration. Serum sodium, chloride, and bicarbonate concentrations and osmolarity also declined significantly in the midluteal phase of the menstrual cycle. Urinary adenosine 3',5'-cyclic monophosphate (cAMP) excretion increased in the luteal compared with the follicular phase, whereas no changes in urinary cGMP or NO2/NO3 excretion were found. Thus peripheral vasodilation occurs in the luteal phase of the normal menstrual cycle in association with an increase in renal plasma flow and filtration. Activation of the renin-angiotensin-aldosterone axis is found in the luteal phase of the menstrual cycle. These changes are accompanied by an increase in urinary cAMP excretion indicating potential vasodilating mediators responsible for the observed hemodynamic changes. PMID:9374841

  17. Involvement of microtubules in lipoprotein degradation and utilization for steroidogenesis in cultured rat luteal cells

    SciTech Connect

    Rajan, V.P.; Menon, K.M.

    1985-12-01

    Cells isolated from superovulated rat ovaries metabolize low density lipoprotein (LDL) and high density lipoprotein (HDL) of human or rat origin and use the lipoprotein-derived cholesterol as a precursor for progesterone production. Under in vitro conditions, both lipoproteins are internalized and degraded in the lysosomes, although degradation of HDL is of lower magnitude than that of LDL. In this report we have examined the role of cellular microtubules in the internalization and degradation of human LDL and HDL in cultured rat luteal cells. The microtubule depolymerizing agents colchicine, podophyllotoxin, vinblastine, and nocodazole as well as taxol, deuterium oxide, and dimethyl sulfoxide, which are known to rapidly polymerize cellular tubulin into microtubules, were used to block the function of microtubules. When these antimicrotubule agents were included in the incubations, degradation of the apolipoproteins of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL by the luteal cells was inhibited by 50-85% compared to untreated control values. Maximum inhibitory effects were observed when the cells were preincubated with the inhibitor for at least 4 h at 37 C before treatment with the labeled lipoprotein. Lipoprotein-stimulated progesterone production by luteal cells was also inhibited by 50% or more in the presence of antimicrotubule agents. However, basal and hCG-stimulated progesterone production were unaffected by these inhibitors. The binding of (/sup 125/I)iodo-LDL and (/sup 125/I)iodo-HDL to luteal cell plasma membrane receptors was not affected by the microtubule inhibitors. Although binding was unaffected and degradation was impaired in the presence of the inhibitors, there was no detectable accumulation of undegraded lipoprotein within the cells during the 24 h of study.

  18. N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.

    PubMed

    Löhrke, Berthold; Xu, Jinxian; Weitzel, Joachim M; Krüger, Burkhard; Goldammer, Tom; Viergutz, Torsten

    2010-04-01

    N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry. PMID:20151456

  19. N-acetylcysteine impairs survival of luteal cells through mitochondrial dysfunction.

    PubMed

    Löhrke, Berthold; Xu, Jinxian; Weitzel, Joachim M; Krüger, Burkhard; Goldammer, Tom; Viergutz, Torsten

    2010-04-01

    N-acetylcysteine (NAC) is known as an antioxidant and used for mucus viscosity reduction. However, this drug prevents or induces cell death depending on the cell type. The response of steroidogenic luteal cells to NAC is unknown. Our data shows that NAC can behave as an antioxidant or prooxidant in dependency on the concentration and mitochondrial energization. NAC elevated the flowcytometric-measured portion of hypodiploid (dying) cells. This rise was completely abolished by aurintricarboxylic acid, an inhibitor of topoisomerase II. NAC increased the secretion of nitric oxide and cellular nitrotyrosine. An image analysis indicated that cells pretreated with NAC and loaded with DHR showed a fluorescent structure probably elicited by the oxidative product of DHR, rhodamine 123 that sequesters mitochondrially. Pretreating luteal cells with NAC or adding NAC directly to mitochondrial fractions followed by assessing the mitochondrial transmembrane potential difference (Deltapsi) by the JC-1 technique demonstrated a marked decrease in Deltapsi. A protonophore restored Deltapsi and rotenone (an inhibitor of respiratory chain complex I) inhibited mitochondrial recovering. Thus, in steroidogenic luteal cells from healthy mature corpus luteum, NAC impairs cellular survival by interfering with mitochondrial metabolism. The protonophore-induced recovering of NAC-provoked decrease in Deltapsi indicates that an ATP synthase-favored route of H(+) re-entry to the matrix is essentially switched off by NAC while other respiratory chain complexes remain intact. These data may be important for therapeutic timing of treatments with NAC. (c) 2010 International Society for Advancement of Cytometry.

  20. Differential action of decidual luteotropin on luteal and follicular production of testosterone and estradiol.

    PubMed

    Gibori, G; Kalison, B; Warshaw, M L; Basuray, R; Glaser, L A

    1985-05-01

    Decidual tissue of the rat produces a hormone with physiological and biochemical characteristics similar to those of PRL. Because PRL affects both follicular and luteal production of testosterone and estradiol, it was of interest to determine whether decidual luteotropin affects basal and/or LH-stimulated ovarian secretion of steroids and whether it differentially affects follicular and luteal synthesis of testosterone and estradiol. The uteri of pseudopregnant adult rats were scratched on day 5 to induce decidual tissue formation. Pseudopregnant animals without decidua were used as controls. Rats were either hypophysectomized on day 8 or left intact. They were treated with 1.5 IU hCG/day or with vehicle between days 8-9. On day 9, blood was obtained from the ovarian vein, and both corpora lutea and large antral follicles were isolated and incubated in vitro. The presence of the decidua significantly suppressed both basal and hCG-stimulated ovarian secretion of estradiol, yet enhanced progesterone production. A similar inhibitory effect of decidual tissue on hCG stimulation of testosterone and estradiol was observed in the hypophysectomized rats. When the effect of decidua on follicles and corpora lutea was studied separately, it was found that follicles of rats with decidua produced significantly less testosterone and estradiol than follicles of rats without decidua. hCG administration to either intact or hypophysectomized rats markedly enhanced the follicular capacity to produce these two steroids. However, the degree of hCG stimulation of follicular steroidogenesis was significantly reduced by the presence of decidual tissue. In contrast, the decidua did not inhibit the in vitro steroidogenic capacity of corpora lutea. Luteal tissue of intact rats with or without decidua produced similar basal amounts of testosterone and estradiol and responded to a hCG challenge with comparable increases in the production of both steroids. After hypophysectomy, however, the

  1. Isolation and characterisation of Kasumi-1 human myeloid leukaemia cell line resistant to tumour necrosis factor alpha-induced apoptosis.

    PubMed Central

    Ido, M.; Hayashi, K.; Kato, S.; Ogawa, H.; Komada, Y.; Zhau, Y. W.; Zhang, X. L.; Sakurai, M.; Suzuki, K.

    1996-01-01

    Tumour necrosis factor (TNF)-alpha induces apoptosis in a human acute myeloid leukaemia cell line, Kasumi-1. To examine the role of protein phosphorylation in signal transduction of TNF-alpha-induced apoptosis, a variant cell line resistant to TNF-alpha was established by an intermittent challenge of Kasumi-1 cells with increasing concentrations of TNF-alpha for 6 months. The mechanism of resistance to TNF-alpha appears to be in the post-receptor pathway because expression of p55 TNF receptor in the variant cells is increased compared with that of the parental Kasumi-1 cells. In renaturation assays, TNF-alpha induced a rapid activation of different protein kinases of different molecular weights, including the 50 kDa protein kinase (PK50) followed by the 35 kDa protein kinase (PK35), in the parental Kasumi-1 cells. The dose-response of TNF-alpha required to activate PK50 and PK35 was closely related to concentrations of TNF-alpha that induced apoptosis. Treatment of Kasumi-1 cells with ceramide also activated PK35. In TNF-resistant variant cells, activation of PK35 in response to TNF-alpha or ceramide was practically nil. These findings suggest that activation of PK35 through the ceramide pathway may play an important role in signal transduction of TNF-alpha in the Kasumi-1 cell line, while the decreased activation of PK35 may explain the insensitivity of the variant cells towards TNF-alpha. Images Figure 3 Figure 4 Figure 5 Figure 6 PMID:8562342

  2. Sphingosine kinase-1 mediates TNF-alpha-induced MCP-1 gene expression in endothelial cells: upregulation by oscillatory flow.

    PubMed

    Chen, Xi-Lin; Grey, Janice Y; Thomas, Suzanne; Qiu, Fei-Hua; Medford, Russell M; Wasserman, Martin A; Kunsch, Charles

    2004-10-01

    Atherosclerosis is a focal inflammatory disease and preferentially occurs in areas of low fluid shear stress and oscillatory flow, whereas the risk of atherosclerosis is decreased in regions of high fluid shear stress and steady laminar flow. Sphingosine kinase-1 (SphK1) catalyzes the conversion of sphingosine to sphingosine-1 phosphate (S1P), a sphingolipid metabolite that plays important roles in angiogenesis, inflammation, and cell growth. In the present study, we demonstrated that exposure of human aortic endothelial cells to oscillatory flow (shear stress, +/-5 dyn/cm(2) for 48 h) resulted in a marked increase in SphK1 mRNA levels compared with endothelial cells kept in static culture. In contrast, laminar flow (shear stress, 20 dyn/cm(2) for 48 h) decreased SphK1 mRNA levels. We further investigated the role of SphK1 in TNF-alpha-induced expression of inflammatory genes, such as monocyte chemoattractant protein-1 (MCP-1) and VCAM-1 by using small interfering RNA (siRNA) specifically for SphK1. Treatment of endothelial cells with SphK1 siRNA suppressed TNF-alpha-induced increase in MCP-1 mRNA levels, MCP-1 protein secretion, and activation of p38 MAPK. SphK1 siRNA also inhibited TNF-alpha-induced cell surface expression of VCAM-1, but not ICAM-1, protein. Exposure of endothelial cells to S1P led to an increase in MCP-1 protein secretion and MCP-1 mRNA levels and activation of NF-kappaB-mediated transcriptional activity. Treatment of endothelial cells with the p38 MAPK inhibitor SB-203580 suppressed S1P-induced MCP-1 protein secretion. These data suggest that SphK1 mediates TNF-alpha-induced MCP-1 gene expression through a p38 MAPK-dependent pathway and may participate in oscillatory flow-mediated proinflammatory signaling pathway in the vasculature. PMID:15191888

  3. Development of a bovine luteal cell in vitro culture system suitable for co-culture with early embryos.

    PubMed

    Batista, M; Torres, A; Diniz, P; Mateus, L; Lopes-da-Costa, L

    2012-10-01

    The cross talk between the corpus luteum (CL) and the early embryo, potentially relevant to pregnancy establishment, is difficult to evaluate in the in vivo bovine model. In vitro co-culture of bovine luteal cells and early embryos (days 2-8 post in vitro fertilization) may allow the deciphering of this poorly understood cross talk. However, early embryos and somatic cells require different in vitro culture conditions. The objective of this study was to develop a bovine luteal cell in vitro culture system suitable for co-culture with early embryos in order to evaluate their putative steroidogenic and prostanoid interactions. The corpora lutea of the different stages of the estrous cycle (early, mid, and late) were recovered postmortem and enriched luteal cell populations were obtained. In experiments 1 and 2, the effects of CL stage, culture medium (TCM, DMEM-F12, or SOF), serum concentration (5 or 10%), atmosphere oxygen tension (5 or 20%), and refreshment of the medium on the ability of luteal cells to produce progesterone (P(4)) were evaluated. The production of P(4) was significantly increased in early CL cultures, and luteal cells adapted well to simple media (SOF), low serum concentrations (5%), and oxygen tensions (5%). In experiment 3, previous luteal cell cryopreservation did not affect the production of P(4), PGF(2α), and PGE(2) compared to fresh cell cultures. This enables the use of pools of frozen-thawed cells to decrease the variation in cell function associated with primary cell cultures. In experiment 4, mineral oil overlaying culture wells resulted in a 50-fold decrease of the P(4) quantified in the medium, but had no effect on PGF(2α) and PGE(2) quantification. In conclusion, a luteal cell in vitro culture system suitable for the 5-d-long co-culture with early embryos was developed.

  4. Development of a bovine luteal cell in vitro culture system suitable for co-culture with early embryos.

    PubMed

    Batista, M; Torres, A; Diniz, P; Mateus, L; Lopes-da-Costa, L

    2012-10-01

    The cross talk between the corpus luteum (CL) and the early embryo, potentially relevant to pregnancy establishment, is difficult to evaluate in the in vivo bovine model. In vitro co-culture of bovine luteal cells and early embryos (days 2-8 post in vitro fertilization) may allow the deciphering of this poorly understood cross talk. However, early embryos and somatic cells require different in vitro culture conditions. The objective of this study was to develop a bovine luteal cell in vitro culture system suitable for co-culture with early embryos in order to evaluate their putative steroidogenic and prostanoid interactions. The corpora lutea of the different stages of the estrous cycle (early, mid, and late) were recovered postmortem and enriched luteal cell populations were obtained. In experiments 1 and 2, the effects of CL stage, culture medium (TCM, DMEM-F12, or SOF), serum concentration (5 or 10%), atmosphere oxygen tension (5 or 20%), and refreshment of the medium on the ability of luteal cells to produce progesterone (P(4)) were evaluated. The production of P(4) was significantly increased in early CL cultures, and luteal cells adapted well to simple media (SOF), low serum concentrations (5%), and oxygen tensions (5%). In experiment 3, previous luteal cell cryopreservation did not affect the production of P(4), PGF(2α), and PGE(2) compared to fresh cell cultures. This enables the use of pools of frozen-thawed cells to decrease the variation in cell function associated with primary cell cultures. In experiment 4, mineral oil overlaying culture wells resulted in a 50-fold decrease of the P(4) quantified in the medium, but had no effect on PGF(2α) and PGE(2) quantification. In conclusion, a luteal cell in vitro culture system suitable for the 5-d-long co-culture with early embryos was developed. PMID:23054443

  5. Inhibition of Delta-Like Ligand 4 Induces Luteal Hypervascularization Followed by Functional and Structural Luteolysis in the Primate Ovary

    PubMed Central

    Hastings, Julie M.; Allan, Deborah; Morris, Keith D.; Rudge, John S.; Wiegand, Stanley J.

    2012-01-01

    Using specific inhibitors established that angiogenesis in the ovarian follicle and corpus luteum is driven by vascular endothelial growth factor. Recently, it has been demonstrated that the Notch ligand, delta-like ligand 4 (Dll4) negatively regulates vascular endothelial growth factor-mediated vessel sprouting and branching. To investigate the role of Dll4 in regulation of the ovarian vasculature, we administered a neutralizing antibody to Dll4 to marmosets at the periovulatory period. The vasculature was examined on luteal d 3 or d 10: angiogenesis was determined by incorporation of bromodeoxyuridine, staining for CD31 and cell death by staining for activated caspase-3. Ovulatory progesterone rises were monitored to determine effects of treatment on luteal function and time to recover normal cycles in a separate group of animals. Additionally, animals were treated in the follicular or midluteal phase to determine effects of Dll4 inhibition on follicular development and luteal function. Controls were treated with human IgG (Fc). Corpora lutea from marmosets treated during the periovulatory period exhibited increased angiogenesis and increased vascular density on luteal d 3, but plasma progesterone was significantly suppressed. By luteal d 10, corpora lutea in treated ovaries were significantly reduced in size, with involution of luteal cells, increased cell death, and suppressed plasma progesterone concentrations. In contrast, initiation of anti-Dll4 treatment during the midluteal phase produced only a slight suppression of progesterone for the remainder of the cycle. Moreover, Dll4 inhibition had no appreciable effect on follicular development. These results show that Dll4 has a specific and critical role in the development of the normal luteal vasculature. PMID:22334711

  6. Novel concepts on the role of prostaglandins on luteal maintenance and maternal recognition and establishment of pregnancy in ruminants.

    PubMed

    Arosh, Joe A; Banu, Sakhila K; McCracken, John A

    2016-07-01

    In ruminants, the corpus luteum (CL) of early pregnancy is resistant to luteolysis. Prostaglandin (PG)E2 is considered a luteoprotective mediator. Early studies indicate that during maternal recognition of pregnancy (MRP) in ruminants, a factor(s) from the conceptus or gravid uterus reaches the ovary locally through the utero-ovarian plexus (UOP) and protects the CL from luteolysis. The local nature of the embryonic antiluteolytic or luteoprotective effect precludes any direct effect of a protein transported or acting between the gravid uterus and CL in ruminants. During MRP, interferon tau (IFNT) secreted by the trophoblast of the conceptus inhibits endometrial pulsatile release of PGF2α and increases endometrial PGE2. Our recent studies indicate that (1) luteal PG biosynthesis is selectively directed toward PGF2α at the time of luteolysis and toward PGE2 at the time of establishment of pregnancy (ESP); (2) the ability of the CL of early pregnancy to resist luteolysis is likely due to increased intraluteal biosynthesis and signaling of PGE2; and (3) endometrial PGE2 is transported from the uterus to the CL through the UOP vascular route during ESP in sheep. Intrauterine co-administration of IFNT and prostaglandin E2 synthase 1 (PGES-1) inhibitor reestablishes endometrial PGF2α pulses and regresses the CL. In contrast, intrauterine co-administration of IFNT and PGES-1 inhibitor along with intraovarian administration of PGE2 rescues the CL. Together, the accumulating information provides compelling evidence that PGE2 produced by the CL in response to endometrial PGE2 induced by pregnancy may counteract the luteolytic effect of PGF2α as an additional luteoprotective mechanism during MRP or ESP in ruminants. Targeting PGE2 biosynthesis and signaling selectively in the endometrium or CL may provide luteoprotective therapy to improve reproductive efficiency in ruminants.

  7. Novel concepts on the role of prostaglandins on luteal maintenance and maternal recognition and establishment of pregnancy in ruminants.

    PubMed

    Arosh, Joe A; Banu, Sakhila K; McCracken, John A

    2016-07-01

    In ruminants, the corpus luteum (CL) of early pregnancy is resistant to luteolysis. Prostaglandin (PG)E2 is considered a luteoprotective mediator. Early studies indicate that during maternal recognition of pregnancy (MRP) in ruminants, a factor(s) from the conceptus or gravid uterus reaches the ovary locally through the utero-ovarian plexus (UOP) and protects the CL from luteolysis. The local nature of the embryonic antiluteolytic or luteoprotective effect precludes any direct effect of a protein transported or acting between the gravid uterus and CL in ruminants. During MRP, interferon tau (IFNT) secreted by the trophoblast of the conceptus inhibits endometrial pulsatile release of PGF2α and increases endometrial PGE2. Our recent studies indicate that (1) luteal PG biosynthesis is selectively directed toward PGF2α at the time of luteolysis and toward PGE2 at the time of establishment of pregnancy (ESP); (2) the ability of the CL of early pregnancy to resist luteolysis is likely due to increased intraluteal biosynthesis and signaling of PGE2; and (3) endometrial PGE2 is transported from the uterus to the CL through the UOP vascular route during ESP in sheep. Intrauterine co-administration of IFNT and prostaglandin E2 synthase 1 (PGES-1) inhibitor reestablishes endometrial PGF2α pulses and regresses the CL. In contrast, intrauterine co-administration of IFNT and PGES-1 inhibitor along with intraovarian administration of PGE2 rescues the CL. Together, the accumulating information provides compelling evidence that PGE2 produced by the CL in response to endometrial PGE2 induced by pregnancy may counteract the luteolytic effect of PGF2α as an additional luteoprotective mechanism during MRP or ESP in ruminants. Targeting PGE2 biosynthesis and signaling selectively in the endometrium or CL may provide luteoprotective therapy to improve reproductive efficiency in ruminants. PMID:27179861

  8. Bupropion for interferon-alpha-induced depression in patients with hepatitis C viral infection: an open-label study.

    PubMed

    Chen, Wei-Chun; Lai, Hsueh-Chou; Su, Wen-Pang; Palani, Mahalakshmi; Su, Kuan-Pin

    2015-01-01

    Interferon (IFN)-α therapy for chronic hepatitis C virus (HCV) infection is frequently associated with major depressive episodes. Bupropion, a commonly used antidepressant agent, has recently found to have strong anti-inflammatory effects in animal models. Despite of the theoretical relevancy, the antidepressant effect of bupropion in IFN-alpha-induced depression has never been studied. Ten HCV patients with IFN-α-induced depression were recruited to receive 8-week bupropion treatment and were assessed every 2 weeks for depressive symptoms by the Hamilton rating scale for depression (HAMD) and somatic symptoms by the Neurotoxicity Rating Scale (NRS). Four of the 10 patients met the criteria for remission (total HAMD scores≤7), and 5 patients met the criteria for response (at least 50% reduction in total HAMD scores). In addition, 5 patients had 50% decreases in NRS for neuropsychiatric symptoms. This preliminary open-label study suggests that bupropion is effective in treating IFN-alpha-induced depressive and somatic symptoms.

  9. Inhibitory effects of ginger oil on spontaneous and PGF2alpha-induced contraction of rat myometrium.

    PubMed

    Buddhakala, Nopparat; Talubmook, Chusri; Sriyotha, Poonsook; Wray, Susan; Kupittayanant, Sajeera

    2008-03-01

    Solvent extracts of ginger, the rhizome of Zingiber officinale Roscoe (Zingiberaceae), have been extensively studied for their pharmacological activities in smooth muscles. However, the effects of ginger essential oil on smooth muscle contractility have not been elucidated. The aims of the study were to investigate the effects of ginger oil on rat myometrial contractility. We particularly examined the effects on phasic contractions arising either spontaneously or with PGF (2) (alpha) stimulation. Ginger oil was obtained by hydrodistillation and its constituents analyzed using gas chromatography and mass spectrometry. Rats were humanely killed by asphyxiation with CO (2), and longitudinal uterine smooth muscles were isolated. Isometric force was measured and the effects of ginger oil studied. It was found that citral was the main constituent of ginger oil (24 %). Ginger oil inhibited spontaneous contractions with an IC (50) of 50 microL/100 mL (10 - 150 microL/100 mL). The PGF (2) (alpha)-induced contractions were also significantly reduced by ginger oil. Increases in external calcium concentration completely reversed the relaxant effects of ginger oil. This was the case for both spontaneous and PGF (2) (alpha)-induced contractions. The effects of ginger oil were indistinguishable from those of pure citral. In conclusion, ginger oil is a potent inhibitor of phasic activity in rat uterus, irrespective of how it was produced. Our data suggest that the effects are largely due to citral, and could be via inhibition of L-type Ca channels. PMID:18484528

  10. The inhibition of TNF-alpha-induced E-selectin expression in endothelial cells via the JNK/NF-kappaB pathways by highly N-acetylated chitooligosaccharides.

    PubMed

    Lin, Chia-Wen; Chen, Li-Jing; Lee, Pei-Ling; Lee, Chih-I; Lin, Jui-Che; Chiu, Jeng-Jiann

    2007-03-01

    Chitooligosaccharides (COS) have been shown to regulate various cellular and biological functions. However, the effect of COS on inflammatory responses of the cells remains unclear. We investigated the regulatory effect of highly N-acetylated COS (NACOS) on tumor necrosis factor-alpha (TNF-alpha)-induced endothelial cell (EC) E-selectin expression, which is crucial for leukocyte recruitment. ECs were kept as controls or pre-treated with NACOS for different times, and then stimulated with TNF-alpha for 4h. The results show that pre-treating ECs with NACOS inhibited the TNF-alpha-induced E-selectin expression in a dose- and time-dependent manner. This NACOS-mediated inhibition in E-selectin expression was regulated at the transcriptional level, but not due to changes in mRNA stability. Stimulation of ECs with TNF-alpha-induced rapid increases in the phosphorylation of their mitogen-activated protein kinases (MAPKs) [extracellular signal-regulated kinase (ERK), c-Jun-NH2-terminal kinase (JNK), and p38 MAPK]; the inhibitor for JNK (i.e., SP600125), but not those for ERK (i.e., PD98059) and p38 MAPK (i.e., SB203580), attenuated this TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced JNK activation, suggesting that JNK was involved in the inhibitory effect of NACOS on TNF-alpha-induced E-selectin expression. Pre-treating ECs with NACOS inhibited the TNF-alpha-induced p65 and p50 mRNA expressions. Gel shifting and chromatin immunoprecipitation assays showed that NACOS blocked the TNF-alpha-induced increases in the binding activity and in vivo promoter binding of nuclear factor-kappaB (NF-kappaB) in ECs. Our findings provide a molecular mechanism by which NACOS inhibit TNF-alpha-induced E-selectin expression in ECs, and a basis for using NACOS in pharmaceutical therapy against inflammation.

  11. Expression and functional implications of luteal endothelins in pregnant and non-pregnant dogs.

    PubMed

    Gram, Aykut; Latter, Sophie; Boos, Alois; Hoffmann, Bernd; Kowalewski, Mariusz P

    2015-11-01

    Luteal development is regulated by many locally produced mediators, e.g., prostaglandins and angiogenic factors. However, the role and function of vasoactive factors in the canine corpus luteum (CL) remain largely unknown. Consequently, expression of the endothelin (ET) receptors-A and -B (ETA and ETB, revealing vasoconstriction and vasodilator properties respectively), the ET-converting enzyme (ECE1) and ET1, -2 and -3 were investigated in CL from non-pregnant dogs (days 5, 15, 25, 35, 45 and 65 post-ovulation), and at selected stages of pregnancy (pre-implantation, post-implantation, mid-gestation), and during normal and antigestagen-induced prepartum luteolysis/abortion. The interrelationship between PGE2 and the ET system was investigated in PGE2-treated canine primary lutein cells from early CL. ET1 did not change significantly over time; ET2, ECE1 and ETB were elevated in early CL and were downregulated towards the mid/late-luteal phase. The prepartum increase of ET2 was significant. ET3 increased gradually, and was highest in late CL and/or at prepartum luteolysis. ETA remained constant until the late CL phase and increased only during prepartum luteolysis. ET1 was localized to the luteal cells, and ET2, ET3 and ETA to vascular endothelium. ECE1 and ETB were detected at both locations. Except for upregulated ET1 and lack of effect on ET2, antigestagen applied to mid-pregnant dogs evoked similar changes to those observed during normal luteolysis. PGE2 upregulated ETB in treated cells; ETA and ET1 remained unaffected, and ET2 decreased. A modulatory role of the ETs in canine CL, possibly in association with other factors (e.g., PGE2 and progesterone receptor), is strongly indicated.

  12. Women Ornament Themselves for Intrasexual Competition near Ovulation, but for Intersexual Attraction in Luteal Phase

    PubMed Central

    Zhuang, Jin-Ying; Wang, Jia-Xi

    2014-01-01

    The present study examined women's attentional bias toward ornamental objects in relation to their menstrual phase as well as to motivations of intersexual courtship or intrasexual competition. In Experiment 1, 33 healthy heterosexual women were tested in a bias-assessment visual cuing task twice: once on a high-fertility day (during the ovulatory phase) and once on a low-fertility day (during the luteal phase). They paid greater attention to pictures of ornamental objects than to pictures of non-ornamental objects near ovulation, but not during the luteal phase, suggesting an ornamental bias during the high-fertility phase. In Experiment 2, before the visual cuing task, 40 participants viewed 10 same-sex or opposite-sex facial photographs with either high or low attractiveness as priming tasks to activate the intrasexual competition or intersexual courtship motives. Results showed that women's ornamental bias was dependent on the interaction of menstrual phase and mating motive. Specifically, the ornamental bias was observed on the high-fertility day when the subjects were primed with high-attractive same-sex images (intrasexual competition) and was observed on the low-fertility day when they were primed with high-attractive opposite-sex photographs (intersexual courtship). In conclusion, the present findings confirm the hypothesis that, during the high-fertility phase, women have an attentional bias toward ornamental objects and further support the hypothesis that the ornamental bias is driven by intrasexual competition motivation near ovulation, but driven by intersexual courtship motivation during the luteal phase. PMID:25180577

  13. Simulated conditions of microgravity suppress progesterone production by luteal cells of the pregnant rat

    NASA Technical Reports Server (NTRS)

    Bhat, G. K.; Yang, H.; Sridaran, R.

    2001-01-01

    The purpose of this study was to assess whether simulated conditions of microgravity induce changes in the production of progesterone by luteal cells of the pregnant rat ovary using an in vitro model system. The microgravity environment was simulated using either a high aspect ratio vessel (HARV) bioreactor with free fall or a clinostat without free fall of cells. A mixed population of luteal cells isolated from the corpora lutea of day 8 pregnant rats was attached to cytodex microcarrier beads (cytodex 3). These anchorage dependent cells were placed in equal numbers in the HARV or a spinner flask control vessel in culture conditions. It was found that HARV significantly reduced the daily production of progesterone from day 1 through day 8 compared to controls. Scanning electron microscopy showed that cells attached to the microcarrier beads throughout the duration of the experiment in both types of culture vessels. Cells cultured in chamber slide flasks and placed in a clinostat yielded similar results when compared to those in the HARV. Also, when they were stained by Oil Red-O for lipid droplets, the clinostat flasks showed a larger number of stained cells compared to control flasks at 48 h. Further, the relative amount of Oil Red-O staining per milligram of protein was found to be higher in the clinostat than in the control cells at 48 h. It is speculated that the increase in the level of lipid content in cells subjected to simulated conditions of microgravity may be due to a disruption in cholesterol transport and/or lesions in the steroidogenic pathway leading to a fall in the synthesis of progesterone. Additionally, the fall in progesterone in simulated conditions of microgravity could be due to apoptosis of luteal cells.

  14. Regression: A Bibliography.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, Bonnie C.

    Regression, another mechanism studied by Sigmund Freud, has had much research, e.g., hypnotic regression, frustration regression, schizophrenic regression, and infra-human-animal regression (often directly related to fixation). Many investigators worked with hypnotic age regression, which has a long history, going back to Russian reflexologists.…

  15. Curcumin inhibits interferon-{alpha} induced NF-{kappa}B and COX-2 in human A549 non-small cell lung cancer cells

    SciTech Connect

    Lee, Jeeyun |; Im, Young-Hyuck | E-mail: imyh@smc.samsung.co.kr; Jung, Hae Hyun; Kim, Joo Hyun; Park, Joon Oh |; Kim, Kihyun |; Kim, Won Seog |; Ahn, Jin Seok

    2005-08-26

    The A549 cells, non-small cell lung cancer cell line from human, were resistant to interferon (IFN)-{alpha} treatment. The IFN-{alpha}-treated A549 cells showed increase in protein expression levels of NF-{kappa}B and COX-2. IFN-{alpha} induced NF-{kappa}B binding activity within 30 min and this increased binding activity was markedly suppressed with inclusion of curcumin. Curcumin also inhibited IFN-{alpha}-induced COX-2 expression in A549 cells. Within 10 min, IFN-{alpha} rapidly induced the binding activity of a {gamma}-{sup 32}P-labeled consensus GAS oligonucleotide probe, which was profoundly reversed by curcumin. Taken together, IFN-{alpha}-induced activations of NF-{kappa}B and COX-2 were inhibited by the addition of curcumin in A549 cells.

  16. Addition of gonadotropin releasing hormone agonist for luteal phase support in in-vitro fertilization: an analysis of 2739 cycles

    PubMed Central

    Şimşek, Erhan; Kılıçdağ, Esra Bulgan; Aytaç, Pınar Çağlar; Çoban, Gonca; Şimşek, Seda Yüksel; Çok, Tayfun; Haydardedeoğlu, Bülent

    2015-01-01

    Objective Luteal phase is defective in in vitro fertilization (IVF) cycles, and many regimens were tried for the very best luteal phase support (LPS). Gonadotropin releasing hormone (GnRH) agonist use, which was administered as an adjunct to the luteal phase support in IVF cycles, was suggested to improve pregnancy outcome measures in certain randomized studies. We analyzed the effects of addition of GnRH agonist to standard progesterone luteal support on pregnancy outcome measures, particularly the live birth rates. Material and Methods This is a retrospective cohort study, including 2739 IVF cycles. Long GnRH agonist and antagonist stimulation IVF cycles with cleavage-stage embryo transfer were included. Cycles were divided into two groups: Group A included cycles with single-dose GnRH agonist plus progesterone LPS and Group B included progesterone only LPS. Live birth rates were the primary outcome measures of the analysis. Miscarriage rates and multiple pregnancy rates were the secondary outcome measures. Results Live birth rates were not statistically different in GnRH agonist plus progesterone (Group A) and progesterone only (Group B) groups in both the long agonist and antagonist stimulation arms (40.8%/41.2% and 32.8%/34.4%, p<0.05 respectively). Moreover, pregnancy rates, implantation rates, and miscarriage rates were found to be similar between groups. Multiple pregnancy rates in antagonist cycles were significantly higher in Group A than those in Group B (12.0% and 6.9%, respectively). Conclusion A beneficial effect of a single dose of GnRH agonist administration as a luteal phase supporting agent is yet to be determined because of the wide heterogeneity of data present in literature. Well-designed randomized clinical studies are required to clarify any effect of luteal GnRH agonist addition on pregnancy outcome measures with different doses, timing, and administration routes of GnRH agonists. PMID:26097392

  17. Transforming growth factor-beta suppresses tumor necrosis factor alpha-induced matrix metalloproteinase-9 expression in monocytes.

    PubMed

    Vaday, G G; Schor, H; Rahat, M A; Lahat, N; Lider, O

    2001-04-01

    The inflammatory response is marked by the release of several cytokines with multiple roles in regulating leukocyte activities, including the secretion of matrix metalloproteinases (MMPs). Although the effects of individual cytokines on monocyte MMP expression have been studied extensively, few studies have examined the influence of combinations of cytokines, which are likely present at inflammatory sites. Herein, we report our investigation of the combinatorial effects of tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta on MMP-9 synthesis. We found that TGF-beta suppressed TNF-alpha-induced MMP-9 secretion by MonoMac-6 monocytic cells in a dose-dependent manner, with a maximal effect of TGF-beta observed at 1 ng/ml. Such suppression was likely regulated at the pretranslational level, because steady-state mRNA levels of TNF-alpha-induced MMP-9 were reduced by TGF-beta, and pulse-chase radiolabeling also showed a decrease in new MMP-9 protein synthesis. The suppressive effects of TGF-beta were time dependent, because short exposures to TNF-alpha before TGF-beta or simultaneous exposure to both cytokines efficiently reduced MMP-9 secretion. Expression of the tissue inhibitor of metalloproteinases (TIMP)-1 and TNF-alpha receptors was unaffected by either cytokine individually or in combination. Affinity binding with radiolabeled TGF-beta demonstrated that levels of TGF-beta receptors were not increased after preincubation with TGF-beta. Suppression of TNFalpha-induced MMP-9 secretion by TGF-beta correlated with a reduction in prostaglandin E2 (PGE2) secretion. Furthermore, the effect of TGF-beta or indomethacin on blockage of TNF-alpha-stimulated MMP-9 production was reversed by the addition of either exogenous PGE2 or the cyclic AMP (cAMP) analogue Bt2cAMP. Thus, we concluded that TGF-beta acts as a potent suppressor of TNF-alpha-induced monocyte MMP-9 synthesis via a PGE2- and cAMP-dependent mechanism. These results suggest that various

  18. Synergistic effect of vasoactive intestinal peptides on TNF-alpha-induced IL-6 synthesis in osteoblasts: amplification of p44/p42 MAP kinase activation.

    PubMed

    Natsume, Hideo; Tokuda, Haruhiko; Mizutani, Jun; Adachi, Seiji; Matsushima-Nishiwaki, Rie; Minamitani, Chiho; Kato, Kenji; Kozawa, Osamu; Otsuka, Takanobu

    2010-05-01

    We previously showed that tumor necrosis factor-alpha (TNF-alpha) stimulates synthesis of interleukin-6 (IL-6), a potent bone resorptive agent, via p44/p42 mitogen-activated protein (MAP) kinase and phosphatidylinositol 3-kinase/Akt in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of vasoactive intestinal peptide (VIP) on TNF-alpha-induced IL-6 synthesis in these cells. VIP, which by itself slightly stimulated IL-6 synthesis, synergistically enhanced the TNF-alpha-induced IL-6 synthesis in MC3T3-E1 cells. The synergistic effect of VIP on the TNF-alpha-induced IL-6 synthesis was concentration-dependent in the range between 1 and 70 nM. We previously reported that VIP stimulated cAMP production in MC3T3-E1 cells. Forskolin, a direct activator of adenylyl cyclase, or 8-bromoadenosine-3',5'-cyclic monophosphate (8bromo-cAMP), a plasma membrane-permeable cAMP analogue, markedly enhanced the TNF-alpha-induced IL-6 synthesis as well as VIP. VIP markedly up-regulated the TNF-alpha-induced p44/p42 MAP kinase phosphorylation. The Akt phosphorylation stimulated by TNF-alpha was only slightly affected by VIP. PD98059, a specific inhibitor of MEK1/2, significantly suppressed the enhancement of TNF-alpha-induced IL-6 synthesis by VIP. The synergistic effect of a combination of VIP and TNF-alpha on the phosphorylation of p44/p42 MAP kinase was diminished by H-89, an inhibitor of cAMP-dependent protein kinase. These results strongly suggest that VIP synergistically enhances TNF-alpha-stimulated IL-6 synthesis via up-regulating p44/p42 MAP kinase through the adenylyl cyclase-cAMP system in osteoblasts.

  19. Effects of arterial infusions of adrenalin and acetylcholine on luteal secretion of progesterone and oxytocin in goats.

    PubMed

    Cooke, R G; Payne, J H

    1998-07-15

    The effects of close intra-arterial infusion of acetylcholine and adrenalin on ovarian secretion of progesterone and oxytocin were examined on Day 10 of the estrous cycle in goats (estrus = Day 0). Acetylcholine (15 micrograms/min) was without effect, but adrenalin (10 micrograms/min) significantly (P < 0.001) raised both progesterone and oxytocin concentrations in ovarian vein plasma. These results show that luteal hormone secretion is enhanced in the goat by beta-adrenergic stimulation and suggest that, as in the sheep and cow, there may be neuroendocrine involvement in the regulation of caprine luteal function. PMID:10734492

  20. Relationship between endometritis and oxidative stress in the follicular fluid and luteal function in the buffalo.

    PubMed

    Behera, B K; Sharma, C G; Singh, S K; Kumar, H; Chaudhari, R K; Mahla, A S; Das, G K; Krishnaswamy, N

    2016-10-01

    In this study, alteration in the follicular fluid composition and luteal function was investigated in the buffalo with endometritis. Genitalia were classified into cytological and purulent endometritis on the basis of polymorphonuclear cell cut off while non-endometritis served as control (n = 10/group). In the follicular phase, the number of surface follicles was counted, diameter of the largest follicle was measured and the follicular fluid was assayed for total protein, cholesterol, malondialdehyde (MDA), total antioxidant capacity (TAC), oestradiol (E2 ) and progesterone (P4 ). The P4 content of corpus luteum during mid-luteal phase was estimated by radioimmunoassay. Ovaries from the follicular phase of oestrous cycle showed no significant difference in the total number of surface follicles, size of the largest follicle and volume of follicular fluid in the buffaloes with and without endometritis (p > .05). However, the antral fluid of the largest follicle from the genitalia of buffalo with cytological and purulent endometritis showed a significant decrease in the concentration of total protein, cholesterol, TAC and E2 and a significant increase in the concentration of MDA and P4 (p < .05). The results indicated that there is an association between endometritis and decreased ovarian function. PMID:27554926

  1. Neurophysin in the large luteal cell of the nonpregnant water buffalo (Bubalus bubalis): immunohistochemical localization.

    PubMed

    Fields, P A; Dubois, W; Shalash, M R; Fields, M J

    1987-12-01

    Light microscopy immunohistochemistry was used to localize neurophysin in the corpus luteum of the mid-luteal phase of the estrous cycle of the water buffalo (Bubalus bubalis). Corpora lutea weighing 0.39-0.65 g from a recent ovulation showed no staining. Corpora lutea identified with the late luteal phase showed only weak evidence of staining. The neurophysin staining was confined to a specific region of large oval-shaped cells (20-30 microns diameter), which had a very eosinophilic cytoplasm. The intense localization of staining to a distinct area of the cytoplasm was previously only observed in the corpus luteum of the cow. Corpora lutea obtained from all quadrants of pregnancy did not stain. Controls in which the neurophysin antiserum was substituted with serum from an unimmunized rabbit (normal rabbit serum) or neurophysin antiserum preabsorbed with bovine oxytocin-associated neurophysin I also did not stain. These data indicate the neurophysin is present in the mature corpus luteum of the nonpregnant water buffalo as it is in other nonpregnant ruminants, the ewe and cow.

  2. Early activation of p38 mitogen activated protein kinase is associated with interferon-alpha-induced depression and fatigue

    PubMed Central

    Felger, Jennifer C.; Alagbe, Oyetunde; Pace, Thaddeus W. W.; Woolwine, Bobbi J.; Hu, Fang; Raison, Charles L.; Miller, Andrew H.

    2011-01-01

    Cytokine-induced stimulation of p38 mitogen activated protein kinase (MAPK) has been shown to influence behaviorally-relevant pathophysiologic pathways including monoamine neurotransmission and neuroendocrine function and thus may contribute to behavioral changes that occur during chronic administration of the innate immune cytokine, interferon (IFN)-alpha. Accordingly, in the current study, phosphorylation (activation) of intracellular p38 MAPK in peripheral blood lymphocytes was analyzed by flow cytometry every 2 hours for 12 hours following the initial injection of IFN-alpha in eleven patients with chronic hepatitis C. Hourly assessments of plasma concentrations of adrenocorticotropic hormone, cortisol and interleukin-6 were also obtained. Symptoms of depression and fatigue were measured at baseline and after 4 and 12 weeks of IFN-alpha treatment. Acute administration of IFN-alpha significantly increased the percentage of lymphocytes staining positive for intracellular phosphorylated p38 (p-p38). IFN-alpha-induced increases in p-p38 were significantly greater in patients that developed clinically significant depressive symptoms [Montgomery Asberg Depression Rating Scale (MADRS) score ≥15] during the first 12 weeks of IFN-alpha treatment. Increases in the percentage of p-p38-positive lymphocytes following the first IFN-alpha injection also highly correlated with depression severity at weeks 4 (r=0.85, p=0.001) and 12 (r=0.70, p=0.018). Similar relationships were observed for fatigue. Examination of relationships between p-p38 induction and factors previously reported to predict IFN-alpha-induced depressive symptoms revealed strong associations of p-p38 with baseline MADRS (r=0.82, p=0.002) and cortisol responses to the initial injection of IFN-alpha (r=0.91, p=0.000). Taken together, these findings indicate that sensitivity of p38 MAPK signaling pathways to immune stimulation is associated with depressive symptoms during chronic IFN-alpha treatment. PMID

  3. GnRH agonist trigger with intensive luteal phase support vs. human chorionic gonadotropin trigger in high responders: an observational study reporting pregnancy outcomes and incidence of ovarian hyperstimulation syndrome.

    PubMed

    Christopoulos, Georgios; Vlismas, Antonios; Carby, Anna; Lavery, Stuart; Trew, Geoffrey

    2016-09-01

    A retrospective, cohort study of high-risk patients undergoing IVF treatment was performed to assess if there is a difference in clinical pregnancy rate, live birth rate and the incidence of ovarian hyperstimulation syndrome, when a GnRH agonist (GnRHa) trigger with intensive luteal support is compared to human chorionic gonadotropin (hCG) with standard luteal support. The control group consisted of 382 high-risk patients having a GnRH antagonist protocol with 194 receiving an hCG trigger. All patients had ≥18 follicles ≥11mm or serum oestradiol >18,000pmol/l on the day of trigger. Patients had a single or double embryo transfer at cleavage or blastocyst stage. Logistic regression was used to adjust for differences between the groups. An intention-to-treat analysis of all cycles was performed. No statistically significant differences were observed in terms of positive pregnancy test, clinical pregnancy rate and live birth rate. Only one patient (0.3%) was hospitalized with severe OHSS in the GnRHa group, compared to 26 patients (13%) in the hCG group. In conclusion, GnRHa trigger is associated with similar pregnancy rates with hCG trigger and a significant reduction in hospitalization for severe OHSS after an intention to treat analysis was performed. PMID:27662416

  4. Targeted disruption of Pten in ovarian granulosa cells enhances ovulation and extends the life span of luteal cells.

    PubMed

    Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S

    2008-09-01

    FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary.

  5. The hypothalamic-pituitary-luteal axis in women: effects of long-term orally active opioid antagonist (naltrexone) administration.

    PubMed

    Fulghesu, A M; Lanzone, A; Apa, R; Guido, M; Ciampelli, M; Cucinelli, F; Caruso, A; Mancuso, S

    1997-01-01

    Aim of our study is to assess the effect of a long-term oral opiate antagonist treatment during the luteal phase on the hypothalamic-pituitary-ovarian axis. Fourteen normovulatory women participated to the study. Immediately after the ovulation, the patients were randomly divided in two groups: in the first one women received naltrexone 50 mg/die orally (Antaxone Zambon Italy) from day 1 of the luteal phase for 7 days. In the second patients were treated with placebo for the same period and served as control group. On day 7, patients were hospitalized for a pulse pattern study followed by a GnRH test. LH, FSH, Estradiol, Progesterone were assayed. The naltrexone administration strongly increased the number as well as the amplitude of the gonadotropin pulses. The circulating P levels were also significantly higher in treated patients. The GnRH injection significantly increases the gonadotropin secretion in all patients. The stimulated LH and FSH secretion was significantly greater in treated patients when compared to controls. Such discharge of LH determined a significant increase of progesterone production in controls, but failed to stimulate the corpus luteum in treated patients. In conclusion the present paper strengthen an important role of the opioidergic system in the regulation of GnRH pulsatility in luteal phase. Moreover, our findings confirms the sensibility of the corpus luteum to LH and the possibility to stimulate the P secretion during the luteal phase.

  6. Targeted Disruption of Pten in Ovarian Granulosa Cells Enhances Ovulation and Extends the Life Span of Luteal Cells

    PubMed Central

    Fan, Heng-Yu; Liu, Zhilin; Cahill, Nicola; Richards, JoAnne S.

    2008-01-01

    FSH activates the phosphatidylinositol-3 kinase (PI3K)/acute transforming retrovirus thymoma protein kinase pathway and thereby enhances granulosa cell differentiation in culture. To identify the physiological role of the PI3K pathway in vivo we disrupted the PI3K suppressor, Pten, in developing ovarian follicles. To selectively disrupt Pten expression in granulosa cells, Ptenfl/fl mice were mated with transgenic mice expressing cAMP response element recombinase driven by Cyp19 promoter (Cyp19-Cre). The resultant Pten mutant mice were fertile, ovulated more oocytes, and produced moderately more pups than control mice. These physiological differences in the Pten mutant mice were associated with hyperactivation of the PI3K/acute transforming retrovirus thymoma protein kinase pathway, decreased susceptibility to apoptosis, and increased proliferation of mutant granulosa cells. Strikingly, corpora lutea of the Pten mutant mice persisted longer than those of control mice. Although the follicular and luteal cell steroidogenesis in Ptenfl/fl;Cyp19-Cre mice was similar to controls, viable nonsteroidogenic luteal cells escaped structural luteolysis. These findings provide the novel evidence that Pten impacts the survival/life span of granulosa/luteal cells and that its loss not only results in the facilitated ovulation but also in the persistence of nonsteroidogenic luteal structures in the adult mouse ovary. PMID:18606860

  7. A comparison of ovarian follicular and luteal cell gene expression profiles provides insight into cellular identities and functions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    After ovulation, somatic cells of the ovarian follicle (theca and granulosa cells) become the small and large luteal cells of the corpus luteum. Aside from known cell type-specific receptors and steroidogenic enzymes, little is known about the differences in the gene expression profiles of these fou...

  8. Wogonin suppresses TNF-{alpha}-induced MMP-9 expression by blocking the NF-{kappa}B activation via MAPK signaling pathways in human aortic smooth muscle cells

    SciTech Connect

    Lee, Syng-Ook; Jeong, Yun-Jeong; Yu, Mi Hee; Lee, Ji-Won; Hwangbo, Mi Hyang; Kim, Cheorl-Ho; Lee, In-Seon . E-mail: inseon@kmu.ac.kr

    2006-12-08

    Matrix metalloproteinase-9 (MMP-9) plays a major role in the pathogenesis of atherosclerosis and restenosis by regulating both migration and proliferation of vascular smooth muscle cells (VSMC) after an arterial injury. In this study, we examined the inhibitory effect of three major flavonoids in Scutellariae Radix, baicalin, baicalein, and wogonin, on TNF-{alpha}-induced MMP-9 expression in human aortic smooth muscle cells (HASMC). Wogonin, but not baicalin and baicalein, significantly and selectively suppressed TNF-{alpha}-induced MMP-9 expression in HASMC. Reporter gene, electrophoretic mobility shift, and Western blotting assays showed that wogonin inhibits MMP-9 gene transcriptional activity by blocking the activation of NF-{kappa}B via MAPK signaling pathways. Moreover, the Matrigel migration assay showed that wogonin reduced TNF-{alpha}-induced HASMC migration. These results suggest that wogonin effectively suppresses TNF-{alpha}-induced HASMC migration through the selective inhibition of MMP-9 expression and represents a potential agent for the prevention of vascular disorders related to the migration of VSMC.

  9. Ginsenosides compound K and Rh(2) inhibit tumor necrosis factor-alpha-induced activation of the NF-kappaB and JNK pathways in human astroglial cells.

    PubMed

    Choi, Kyungsun; Kim, Myungsun; Ryu, Jeonghee; Choi, Chulhee

    2007-06-21

    Ginsenosides, the main component of Panax ginseng, have been known for the anti-inflammatory and anti-proliferative activities. In this study, we investigated the molecular mechanisms responsible for the anti-inflammatory effects of ginsenosides on activated astroglial cells. Among 13 different ginsenosides, intestinal bacterial metabolites Rh(2) and compound K (C-K) showed a significant inhibitory effect on tumor necrosis factor-alpha (TNF-alpha)-induced expression of intercellular adhesion molecule-1 in human astroglial cells. Pretreatment with C-K or Rh(2) suppressed TNF-alpha-induced phosphorylation of IkappaBalpha kinase and the subsequent phosphorylation and degradation of IkappaBalpha. Additionally, the same treatment inhibited TNF-alpha-induced phosphorylation of MKK4 and the subsequent activation of the JNK-AP-1 pathway. The inhibitory effect of ginsenosides on TNF-alpha-induced activation of the NF-kappaB and JNK pathways was not observed in human monocytic U937 cells. These results collectively indicate that ginsenoside metabolites C-K and Rh(2) exert anti-inflammatory effects by the inhibition of both NF-kappaB and JNK pathways in a cell-specific manner.

  10. IFN-{gamma} sensitizes MIN6N8 insulinoma cells to TNF-{alpha}-induced apoptosis by inhibiting NF-{kappa}B-mediated XIAP upregulation

    SciTech Connect

    Kim, Hun Sik; Kim, Sunshin; Lee, Myung-Shik . E-mail: mslee@smc.samsung.co.kr

    2005-10-28

    Although X-linked inhibitor of apoptosis protein (XIAP) is an important intracellular suppressor of apoptosis in a variety of cell types, its role in cytokine-induced pancreatic {beta}-cell apoptosis remains unclear. Here, we found that: (i) XIAP level was inversely correlated with tumor necrosis factor (TNF)-{alpha}-induced apoptosis in MIN6N8 insulinoma cells; (ii) adenoviral XIAP overexpression abrogated the TNF-{alpha}-induced apoptosis through inhibition of caspase activity; (iii) downregulation of XIAP by antisense oligonucleotide or Smac peptide sensitized MIN6N8 cells to TNF-{alpha}-induced apoptosis; (iv) XIAP expression was induced by TNF-{alpha} through a nuclear factor-{kappa}B (NF-{kappa}B)-dependent pathway, and interferon (IFN)-{gamma} prevented such an induction in a manner independent of NF-{kappa}B, which presents a potential mechanism underlying cytotoxic IFN-{gamma}/TNF-{alpha} synergism. Taken together, our results suggest that XIAP is an important modulator of TNF-{alpha}-induced apoptosis of MIN6N8 cells, and XIAP regulation in pancreatic {beta}-cells might play an important role in pancreatic {beta}-cell apoptosis and in the pathogenesis of type 1 diabetes.

  11. TNF-alpha and IL-1alpha induce apoptosis in subconfluent rat mesangial cells. Evidence for the involvement of hydrogen peroxide and lipid peroxidation as second messengers.

    PubMed

    Böhler, T; Waiser, J; Hepburn, H; Gaedeke, J; Lehmann, C; Hambach, P; Budde, K; Neumayer, H H

    2000-07-01

    Apoptosis of mesangial cells (MC) plays a role in glomerulonephritis (GN). In this study we investigated cytokine-induced apoptosis of cultured rat MC by morphological and biochemical features. TNF-alpha and IL-1alpha induced apoptosis in rat MC in a time- and concentration-dependent fashion. RT-PCR experiments revealed that MC express the TNF-receptor 1 (p60) gene constitutively. TNF-alpha as well as IL-1alpha stimulated the production of reactive oxygen species (ROS) and induced lipid peroxidation. Coincubation with catalase inhibited TNF-alpha and IL-1alpha induced apoptosis as well as lipid peroxidation. TNF-alpha, but not IL-1alpha increased the expression of c-jun. These results provide evidence that TNF-alpha and IL-1alpha induce apoptosis in rat MC with hydrogen peroxide and lipid peroxidation as second messengers. Increased c-jun expression may be a downstream intracellular signal of TNF-alpha-, but not IL-1alpha-induced apoptosis.

  12. Transforming growth factor-alpha-induced transcriptional activation of the vascular permeability factor (VPF/VEGF) gene requires AP-2-dependent DNA binding and transactivation.

    PubMed Central

    Gille, J; Swerlick, R A; Caughman, S W

    1997-01-01

    The endothelial cell-specific mitogen vascular permeability factor/vascular endothelial growth factor (VPF/VEGF) represents a central regulator of cutaneous angiogenesis. Increased VPF/VEGF expression has recently been reported in psoriatic skin and healing wounds, both conditions in which transforming growth factor-alpha (TGF alpha) and its ligand, the epidermal growth factor receptor, are markedly up-regulated. Since TGF alpha strongly induces VPF/VEGF synthesis in keratinocytes, TGF alpha-mediated VPF/VEGF expression is likely to play a significant role in the initiation and maintenance of increased vascular hyperpermeability and hyperproliferation in skin biology. The objectives of the present studies were to determine the molecular mechanisms responsible for TGF alpha-induced transcriptional activation of the VPF/VEGF gene. We have identified a GC-rich TGF alpha-responsive region between -88 bp and -65 bp of the VPF/VEGF promoter that is necessary for constitutive and TGF alpha-inducible transcriptional activation. In electrophoretic mobility shift assays, this region binds Sp1-dependent protein complexes constitutively and an additional TGF alpha-inducible protein complex that is distinct from Sp1 protein. Both AP-2 and Egr-1 transcription factors were detected as components of the TGF alpha-inducible protein complex in supershift EMSA studies. In co-transfection studies, an AP-2 but not an Egr-1 expression vector activated VPF/VEGF transcription, thus indicating that AP-2 protein is functionally important in TGF alpha-induced VPF/VEGF gene expression. By clarifying regulatory mechanisms that are critical for angiogenic processes in the skin, these studies may form the basis for new therapeutic strategies to modulate VPF/VEGF expression in cutaneous inflammation and wound healing. PMID:9049304

  13. 5-caffeoylquinic acid and caffeic acid down-regulate the oxidative stress- and TNF-alpha-induced secretion of interleukin-8 from Caco-2 cells.

    PubMed

    Zhao, Zhaohui; Shin, Hee Soon; Satsu, Hideo; Totsuka, Mamoru; Shimizu, Makoto

    2008-05-28

    Although chlorogenic acid (CHA) easily reaches a millimolar level in the gastrointestinal tract because of its high concentration in coffee and fruits, its effects on intestinal epithelial cells have been little reported. We investigated in this study the down-regulative effects of 5-caffeoylquinic acid (CQA), the predominant isomer of CHA, on the H(2)O(2-) or TNF-alpha-induced secretion of interleukin (IL)-8, a central pro-inflammatory chemokine involved in the pathogenesis of inflammatory bowel diseases, in human intestinal epithelial Caco-2 cells. After the cells had been pre- and simultaneously treated with CQA, the oversecretion of IL-8 and overexpression of its mRNA induced by H(2)O(2) were significantly suppressed in a dose-dependent manner in the range of 0.25-2.00 mmol/L. We further found that a metabolite of CQA, caffeic acid (CA), but not quinic acid, significantly inhibited the H(2)O(2)-induced IL-8 secretion and its mRNA expression in the same dose-dependent manner. Both CQA and CA suppressed the TNF-alpha-induced IL-8 secretion as well. Caffeic acid at 2.00 mmol/l was able to absolutely block the H(2)O(2)- or TNF-alpha-induced oversecretion of IL-8 in Caco-2 cells. However, CQA and CA did not suppress the TNF-alpha-induced increase in the IL-8 mRNA expression, indicating that the suppressive mechanisms are different between TNF-alpha-induced and H(2)O(2)-induced IL-8 production models. These results suggest that the habit of drinking coffee and/or eating fruits with a high CHA content may be beneficial to humans in preventing the genesis of inflammatory bowel diseases.

  14. Relationship between luteinizing hormone and decidual luteotropin in the maintenance of luteal steroidogenesis.

    PubMed

    Jayatilak, P G; Glaser, L A; Warshaw, M L; Herz, Z; Gruber, J R; Gibori, G

    1984-10-01

    Between Days 6-11 of pregnancy or pseudopregnancy, the decidual tissue of the rat produces a prolactin-like hormone, decidual luteotropin, which can sustain luteal progesterone production when prolactin is suppressed. However, this effect is dependent upon the presence of the pituitary. The present investigation was undertaken to determine whether decidual luteotropin and luteinizing hormone (LH) act together to sustain luteal steroidogenesis and if so, to find out whether the need for LH is due to the inability of the decidual tissue to produce LH-like material and/or whether LH affects decidual luteotropin production. Pseudopregnant rats with or without decidual tissue were hypophysectomized on Day 8 and treated with either 1.5 IU human chorionic gonadotropin (hCG)/day or with vehicle. Within 24 h, serum progesterone dropped in both vehicle-treated groups and decidual luteotropin levels declined by 80% in the decidual tissue. Human CG administration had no effect on progesterone production in the control group. Yet in rats with decidual tissue, hCG stimulated progesterone production for at least 48 h and maintained the decidual tissue content of decidual luteotropin. Progesterone, but not hCG treatment, maintained decidual luteotropin concentrations in ovariectomized rats. To compare the luteotropic activity of the decidual tissue with that of the placenta, pregnant or pseudopregnant rats with decidual tissue were hypophysectomized on Day 8 and treated with 1.5 IU hCG. Control groups had decidual tissue or placentas removed and were similarly treated. Human CG stimulated progesterone production only in rats with placental or decidual tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. TNF-alpha-induced apoptosis is prevented by erythropoietin treatment on SH-SY5Y cells

    SciTech Connect

    Pregi, Nicolas Wenker, Shirley; Vittori, Daniela; Leiros, Claudia Perez; Nesse, Alcira

    2009-02-01

    The growth factor erythropoietin (Epo) has shown neuronal protective action in addition to its well known proerythroid activity. Furthermore, Epo has dealt with cellular inflammation by inhibiting the expression of several proinflammatory cytokines, such as IL-1 and TNF-{alpha}. The action of TNF can have both apoptotic and antiapoptotic consequences due to altered balance between different cell signalling pathways. This work has focused on the apoptotic effects of this cytokine and the potential protective action of Epo. The model we used was neuroblastoma SH-SY5Y cells cultured in the presence of 25 ng/ml TNF-{alpha} or pretreated with 25 U/ml Epo for 12 h before the addition of TNF-{alpha}. Apoptosis was evaluated by differential cell count after Hoechst staining, analysis of DNA ladder pattern, and measurement of caspase activity. Despite its ability to induce NF-{kappa}B nuclear translocation, TNF-{alpha} induced cell death, which was found to be associated to upregulation of TNF Receptor 1 expression. On the other hand, cells activated by Epo became resistant to cell death. Prevention of death receptor upregulation and caspase activation may explain this antiapoptotic effect of Epo, which may be also favoured by the induction of a higher expression of protective factors, such as Bcl-2 and NF-{kappa}B, through mechanisms involving Jak/STAT and PI3K signalling pathways.

  16. Pregnancy prediction on the day of embryo transfer (Day 7) and Day 14 by measuring luteal blood flow in dairy cows.

    PubMed

    Kanazawa, Tomomi; Seki, Motohide; Ishiyama, Keiki; Kubo, Tomoaki; Kaneda, Yoshiyuki; Sakaguchi, Minoru; Izaike, Yoshiaki; Takahashi, Toru

    2016-10-01

    This study aimed to assess the suitability of luteal blood flow analyses measured by color Doppler ultrasonography (CDUS), to predict pregnancy at pre- and post-embryo transfer (ET) in dairy cows, and to compare with the established criterion like luteal size and plasma progesterone (P4) concentrations. Lactating Holstein cows (n = 65) with spontaneous (n = 34) or synchronized estrus (n = 31) were examined. Cows with a CL greater than or equal to 20 mm in diameter (n = 58) received embryo transfer on Day 7 (Day 0 = estrus). Brightness mode images were captured for calculation of the CL area, luteal cavity area, and dominant follicle area on Days 3, 5, 7, and 14. Color Doppler ultrasonography examinations were conducted to determine the blood flow area (BFA) within the CL at the maximum diameter and the time-averaged maximum velocity (TAMV) of the base of the spiral artery on the same days. Plasma P4 concentrations were determined from blood samples collected at each ultrasound examination. Pregnancy was diagnosed by an ultrasound on Day 30. There was no significant difference in the proportion of cows received embryo (91.2% vs. 87.1%, P = 0.70) and pregnancy rate (58.1% vs. 59.3%, P = 1.00) between the spontaneous estrus and synchronized groups. The BFA values of the pregnant group (n = 34) were approximately 1.42 and 1.54 times higher than those of the nonpregnant group (n = 24) on Days 7 (0.54 ± 0.04 cm(2) vs. 0.38 ± 0.02 cm(2); P < 0.01) and 14 (0.80 ± 0.23 cm(2) vs. 0.52 ± 0.22 cm(2); P < 0.01), respectively. The TAMV of the pregnant group was approximately 1.45 times higher than that of the nonpregnant group on Day 14 (57.8 ± 3.5 cm/s vs. 40.0 ± 3.3 cm/s; P < 0.01). However, no differences were found in the CL area, CL tissue area, dominant follicle area, and plasma P4 concentrations among these groups. In addition, the best logistic regression model to predict pregnancy included scores for BFA on Day 7, BFA and

  17. Differential involvement of 5-HT(1A) and 5-HT(1B/1D) receptors in human interferon-alpha-induced immobility in the mouse forced swimming test.

    PubMed

    Zhang, Hongmei; Wang, Wei; Jiang, Zhenzhou; Shang, Jing; Zhang, Luyong

    2010-01-01

    Although Interferon-alpha (IFN-alpha, CAS 9008-11-1) is a powerful drug in treating several viral infections and certain tumors, a considerable amount of neuropsychiatric side-effects such as depression and anxiety are an unavoidable consequence. Combination with the selective serotonin (5-HT) reuptake inhibitor (SSRI) fluoxetine (CAS 56296-78-7) significantly improved the situation. However, the potential 5-HT(1A) receptor- and 5-HT(1B) receptor-signals involved in the antidepressant effects are still unclear. The effects of 5-HT(1A) receptor- and 5-HT(1B) receptor signals were analyzed by using the mouse forced swimming test (FST), a predictive test of antidepressant-like action. The present results indicated that (1) fluoxetine (administrated intragastrically, 30 mg/kg; not subactive dose: 15 mg/kg) significantly reduced IFN-alpha-induced increase of the immobility time in the forced swimming test; (2) 5-HT(1A) receptor- and 5-HT(1B) receptor ligands alone or in combination had no effects on IFN-alpha-induced increase of the immobility time in the FST; (3) surprisingly, WAY 100635 (5-HT(1A) receptor antagonist, 634908-75-1) and 8-OH-DPAT(5-HT(1A) receptor agonist, CAS 78950-78-4) markedly enhanced the antidepressant effect of fluoxetine at the subactive dose (15 mg/kg, i. g.) on the IFN-alpha-treated mice in the FST. Further investigations showed that fluoxetine combined with WAY 100635 and 8-OH-DPAT failed to produce antidepressant effects in the FST. (4) Co-application of CGS 12066A (5-HT(1B) receptor agonist, CAS 109028-09-3) or GR 127935 (5-HT(1B/1D) receptor antagonist, CAS 148642-42-6) with fluoxetine had no synergistic effects on the IFN-alpha-induced increase of immobility time in FST. (5) Interestingly, co-administration of GR 127935, WAY 100635 and fluoxetine significantly reduced the IFN-alpha-induced increase in immobility time of FST, being more effective than co-administration of WAY 100635 and fluoxetine. All results suggest that (1) compared to

  18. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    PubMed Central

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat

    2016-01-01

    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes. PMID:27679825

  19. The effect of luteal phase gonadotropin-releasing hormone antagonist administration on IVF outcomes in women at risk of OHSS

    PubMed Central

    Eftekhar, Maryam; Miraj, Sepideh; Mortazavifar, Zahrasadat

    2016-01-01

    Background: Gonadotropin-releasing hormone (GnRH) plays essential roles in embryo implantation, invasion of trophoblastic tissue, and steroid synthesis in the placenta. Objective: The aim of this study was to evaluate the effect of GnRH antagonist administration on pregnancy outcomes in early implantation period. Materials and Methods: In this retrospective study, 94 infertile women undergoing GnRH antagonist protocol who were at risk of ovarian hyperstimulation syndrome (OHSS) were included. Sixty-seven patients (group I) received Cetrorelix 0.25 mg/daily in the luteal phase for 3 days while in 27 participants (group II), it was not administered. Pregnancy outcomes were assessed based on chemical and clinical pregnancy rates. Results: The pregnancy outcomes were not significantly different between two groups (p=0.224). Conclusion: The present study proposed that luteal phase GnRH antagonist administration does not influence the chance of successful pregnancy outcomes.

  20. Unitary Response Regression Models

    ERIC Educational Resources Information Center

    Lipovetsky, S.

    2007-01-01

    The dependent variable in a regular linear regression is a numerical variable, and in a logistic regression it is a binary or categorical variable. In these models the dependent variable has varying values. However, there are problems yielding an identity output of a constant value which can also be modelled in a linear or logistic regression with…

  1. NCCS Regression Test Harness

    SciTech Connect

    Tharrington, Arnold N.

    2015-09-09

    The NCCS Regression Test Harness is a software package that provides a framework to perform regression and acceptance testing on NCCS High Performance Computers. The package is written in Python and has only the dependency of a Subversion repository to store the regression tests.

  2. Comparative profiling of differentially expressed microRNAs between the follicular and luteal phases ovaries of goats.

    PubMed

    Zhu, Long; Chen, Tao; Sui, Menghua; Han, Chunyang; Fang, Fugui; Ma, Yuehui; Chu, Mingxing; Zhang, Xiaorong; Liu, Cuiyan; Ling, Yinghui

    2016-01-01

    To explore if the regulation at post-transcriptional level of follicular phase (Fols) to luteal phase (Luts) transition occurs in the ovaries of Anhuai goats, the differentially expressed microRNAs (miRNAs) of ovaries in the Fols and Luts were analyzed using Solexa sequencing in the study. In total, 320 known miRNAs were co-expressed in the two phases, 339 and 353 known miRNAs were expressed in the ovary in the Fols and Luts, respectively. In addition, 45 novel miRNAs were co-expressed in the two phases, 70 and 94 novel miRNAs were expressed in the ovary in the Fols and Luts, respectively. Let-7f was the highest expressed significantly different known miRNA in the two phases, and mir-159 was the highest expressed significantly different novel miRNA in the two phases, which may participate in the follicular-luteal transition of Anhuai goats. GO annotation and KEGG pathway analysis were applied to analyze the target genes of differentially expressed miRNAs detected in the two phases. The results will help to further understand the role of miRNAs in the regulation of follicular to luteal transition in goat ovaries. PMID:27610292

  3. Sweet taste threshold for sucrose inversely correlates with depression symptoms in female college students in the luteal phase.

    PubMed

    Nagai, Masanori; Matsumoto, Sayaka; Endo, Junko; Sakamoto, Reiko; Wada, Maki

    2015-03-15

    Influences of depression symptoms on the sweet taste threshold were investigated in healthy college students (30 males and 40 females). Depression symptoms were scored by SDS (Self-Rating Depression Scale), and anxiety levels by STAI (State- and Trait-Anxiety Inventory). Recognition thresholds for sucrose were determined. In female students, the menstrual phase on the day of the experiment was self-reported. Depression symptoms, anxiety levels, and the recognition threshold for sucrose were not different among the 3 groups, i.e. males, females in the follicular phase, and females in the luteal phase. Depression symptoms were positively correlated with state and trait anxiety in all groups. The sweet taste threshold was inversely correlated with depression symptoms (r=-0.472, p=0.031) and trait anxiety (r=-0.506, p=0.019) in females in the luteal phase. In males as well as females in the follicular phase, however, no correlation between sweet taste threshold and depression was found. The results show that the recognition threshold for sucrose reduces with increased depression in females with a higher anxiety trait, but only in the luteal phase. It is hypothesized that brain regions, which spatially overlap and are responsible for both aversive emotions and gustatory processing, are susceptible to periodic changes in gonadal hormones due to the menstrual cycle. PMID:25576640

  4. Transcriptional Profiling of Human Endocervical Tissues Reveals Distinct Gene Expression in the Follicular and Luteal Phases of the Menstrual Cycle.

    PubMed

    Yildiz-Arslan, Sevim; Coon, John S; Hope, Thomas J; Kim, J Julie

    2016-06-01

    The endocervix plays an important role in providing appropriate protective mechanisms of the upper female reproductive tract (FRT) while at the same time providing the appropriate milieu for sperm transport. Hormone fluctuations throughout the menstrual cycle contribute to changes in the mucosal environment that render the FRT vulnerable to infectious diseases. The objective of this study was to identify genes in human endocervix tissues that were differentially expressed in the follicular versus the luteal phases of the menstrual cycle using gene expression profiling. A microarray using the IIlumina platform was performed with eight endocervix tissues from follicular and four tissues from luteal phases of the menstrual cycle. Data analysis revealed significant differential expression of 110 genes between the two phases, with a P value <0.05 and a fold change cutoff of 1.5. Categorization of these genes, using Ingenuity Pathway Analysis, MetaCore from Thomson Reuters, and DAVID, revealed genes associated with extracellular matrix remodeling and cell-matrix interactions, amino acid metabolism, and lipid metabolism, as well as immune regulation in the follicular phase tissues. In luteal phase tissues, genes associated with chromatin remodeling, inflammation, angiogenesis, oxidative stress, and immune cell regulation were predominately expressed. Using samples from additional patients' tissues, select genes were confirmed by quantitative real-time PCR; immunohistochemical staining was also done to examine protein levels. This is the first microarray analysis comparing gene expression in endocervix tissues in cycling women. This study identified key genes and molecular pathways that were differentially regulated during the menstrual cycle.

  5. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis.

  6. Fully Regressive Melanoma

    PubMed Central

    Ehrsam, Eric; Kallini, Joseph R.; Lebas, Damien; Modiano, Philippe; Cotten, Hervé

    2016-01-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  7. The IL-6/sIL-6R treatment of a malignant melanoma cell line enhances susceptibility to TNF-{alpha}-induced apoptosis

    SciTech Connect

    Wagley, Yadav; Yoo, Yung-Choon; Seo, Han Geuk; Rhee, Man Hee; Kim, Tae-Hyoung; Kang, Keon Wook; Nah, Seung-Yeol; Oh, Jae-Wook . E-mail: ohjw@mail.chosun.ac.kr

    2007-03-23

    Melanoma is an intractable tumor that has shown very impressive and promising response to local administration of high dose recombinant TNF-{alpha} in combination with IFN-{gamma} in clinical studies. In this study, we investigated the effect of IL-6/sIL-6R on TNF-{alpha}-resistant B16/F10.9 melanoma cells. A low dose of TNF-{alpha} or IL-6/sIL-6R had minimal affect on the cell growth. However, the highly active fusion protein of sIL-6R and IL-6 (IL6RIL6), covalently linked by a flexible peptide, sensitized TNF-{alpha}-resistant F10.9 melanoma cells to TNF-{alpha}-induced apoptosis. Stimulation of the cells with IL6RIL6 plus TNF-{alpha} resulted in both the activation of caspase-3 and the reduction of bcl-2 expression. Flow cytometry analysis showed that IL6RIL6-upregulated TNF-R55 and TNF-R75 expression, suggesting an increase in TNF-{alpha} responsiveness by IL6RIL6 resulting from the induction of TNF receptors. Moreover, exposure of F10.9 cells to neutralizing antibody to TNF-R55 significantly inhibited IL6RIL6/TNF-{alpha}-induced cytotoxicity. These results suggest that the IL6/sIL6R/gp130 system, which sensitizes TNF-{alpha}-resistant melanoma cells to TNF-{alpha}-induced apoptosis, may provide a new target for immunotherapy.

  8. Infection of human fallopian tube epithelial cells with Neisseria gonorrhoeae protects cells from tumor necrosis factor alpha-induced apoptosis.

    PubMed

    Morales, Priscilla; Reyes, Paz; Vargas, Macarena; Rios, Miguel; Imarai, Mónica; Cardenas, Hugo; Croxatto, Horacio; Orihuela, Pedro; Vargas, Renato; Fuhrer, Juan; Heckels, John E; Christodoulides, Myron; Velasquez, Luis

    2006-06-01

    Following infection with Neisseria gonorrhoeae, bacteria may ascend into the Fallopian tubes (FT) and induce salpingitis, a major cause of infertility. In the FT, interactions between mucosal epithelial cells and gonococci are pivotal events in the pathogen's infection cycle and the inflammatory response. In the current study, primary FT epithelial cells were infected in vitro with different multiplicities of infection (MOI) of Pil+ Opa+ gonococci. Bacteria showed a dose-dependent association with cells and induced the secretion of tumor necrosis factor alpha (TNF-alpha). A significant finding was that gonococcal infection (MOI = 1) induced apoptosis in approximately 30% of cells, whereas increasing numbers of bacteria (MOI = 10 to 100) did not induce apoptosis. Apoptosis was observed in only 11% of cells with associated bacteria, whereas >84% of cells with no adherent bacteria were apoptotic. TNF-alpha was a key contributor to apoptosis, since (i) culture supernatants from cells infected with gonococci (MOI = 1) induced apoptosis in naïve cultures, suggesting that a soluble factor was responsible; (ii) gonococcal infection-induced apoptosis was inhibited with anti-TNF-alpha antibodies; and (iii) the addition of exogenous TNF-alpha induced apoptosis, which was inhibited by the presence of increasing numbers of bacteria (MOI = 10 to 100). These data suggest that TNF-alpha-mediated apoptosis of FT epithelial cells is likely a primary host defense mechanism to prevent pathogen colonization. However, epithelial cell-associated gonococci have evolved a mechanism to protect the cells from undergoing TNF-alpha-mediated apoptosis, and this modulation of the host innate response may contribute to establishment of infection. Understanding the antiapoptotic mechanisms used by Neisseria gonorrhoeae will inform the pathogenesis of salpingitis and could suggest new intervention strategies for prevention and treatment of the disease. PMID:16714596

  9. Tumor Necrosis Factor-alpha Induced Protein 3 Interacting Protein 1 Gene Polymorphisms and Pustular Psoriasis in Chinese Han Population

    PubMed Central

    Han, Jian-Wen; Wang, Yong; Alateng, Chulu; Li, Hong-Bin; Bai, Yun-Hua; Lyu, Xin-Xiang; Wu, Rina

    2016-01-01

    Background: Psoriasis is a common immune-mediated inflammatory dermatosis. Generalized pustular psoriasis (GPP) is the severe and rare type of psoriasis. The association between tumor necrosis factor-alpha induced protein 3 interacting protein 1 (TNIP1) gene and psoriasis was confirmed in people with multiple ethnicities. This study was to investigate the association between TNIP1 gene polymorphisms and pustular psoriasis in Chinese Han population. Methods: Seventy-three patients with GPP, 67 patients with palmoplantar pustulosis (PPP), and 476 healthy controls were collected from Chinese Han population. Six single nucleotide polymorphisms (SNPs) of the TNIP1 gene, namely rs3805435, rs3792798, rs3792797, rs869976, rs17728338, and rs999011 were genotyped by using polymerase chain reaction-ligase detection reaction. Statistical analyses were performed using the PLINK 1.07 package. Allele frequencies and genotyping frequencies for six SNPs were compared by using Chi-square test, odd ratio (OR) (including 95% confidence interval) were calculated. The haplotype analysis was conducted by Haploview software. Results: The frequencies of alleles of five SNPs were significantly different between the GPP group and the control group (P ≤ 7.22 × 10−3), especially in the GPP patients without psoriasis vulgaris (PsV). In the haplotype analysis, the most significantly different haplotype was H4: ACGAAC, with 13.1% frequency in the GPP group but only 3.4% in the control group (OR = 4.16, P = 4.459 × 10−7). However, no significant difference in the allele frequencies was found between the PPP group and control group for each of the six SNPs (P > 0.05). Conclusions: Polymorphisms in TNIP1 are associated with GPP in Chinese Han population. However, no association with PPP was found. These findings suggest that TNIP1 might be a susceptibility gene for GPP. PMID:27364786

  10. Corpus luteal contribution to maternal pregnancy physiology and outcomes in assisted reproductive technologies.

    PubMed

    Conrad, Kirk P; Baker, Valerie L

    2013-01-15

    Investigations in the rat model of pregnancy indicate an important role for the corpus luteal (CL) hormone relaxin in the maternal circulatory and osmoregulatory changes in pregnancy, which are epitomized by profound vasodilation and modest hypoosmolality, respectively. In a pilot study of infertile women who became pregnant through donor eggs, in vitro fertilization, and embryo transfer, the gestational rise in glomerular filtration and fall in plasma osmolality were markedly subdued. Because these women were infertile, they lacked a CL and circulating relaxin (and possibly other vasoactive CL hormones). Based on these findings in pregnant rats and women, we hypothesize that infertile women conceiving through donor eggs will have overall subdued circulatory changes (e.g., attenuated reduction in systemic vascular resistance and subdued increase in cardiac output) particularly during early pregnancy when CL hormones predominate before the full development and maturation of the placenta. In contrast, infertile women conceiving by autologous eggs retrieved after ovarian stimulation and fresh embryo transfer may have a relatively hyperdynamic circulation due to the presence of many CL (up to 20 or more) and higher circulating levels of vasodilatory ovarian hormones such as relaxin. Emerging evidence suggests that women undergoing Assisted Reproductive Technologies (ART) have increased risk for adverse pregnancy outcomes such as preeclampsia and small for gestational-age babies. This increased risk may be partly caused by the maternal milieu, which is not physiological in ART pregnancies due to the abnormal status of the CL.

  11. Comparison of intravaginal progesterone gel and intramuscular 17-α-hydroxyprogesterone caproate in luteal phase support

    PubMed Central

    SATIR, FUNDA; TOPTAS, TAYFUN; INEL, MURAT; ERMAN-AKAR, MUNIRE; TASKIN, OMUR

    2013-01-01

    The main objective of this study was to compare the pregnancy rates of intramuscular (IM) 17-α-hydroxyprogesterone caproate (17-HPC) and intravaginal (IV) progesterone gel administration in in vitro fertilization-embryo transfer (IVF-ET) cycles. The IM 17-HPC and IV progesterone groups included 632 (66.4%) and 320 (33.6%) women undergoing the first cycles of IVF-ET treatment, respectively. Multivariate analyses annotated for all potential confounders showed that the use of IV progesterone retained a predictive value for the total β-human chorionic gonadotropin (hCG) positivity and clinical pregnancy rates [adjusted odds ratio (OR), 1.97; 95% confidence interval (CI), 1.28–3.03; P=0.002; and OR, 1.66; 95% CI, 1.07–2.60; P=0.03, respectively]. However, biochemical and on-going pregnancy rates did not differ significantly between the groups (OR, 1.85; 95% CI, 1.00–3.41; P=0.05; and OR, 1.43, 95% CI, 0.89–2.30; P=0.14, respectively). Luteal phase support (LPS) with IV progesterone gel in comparison with IM 17-HPC appears to be associated with higher clinical pregnancy rates in IVF-ET cycles. However, this benefit is clinically irrelevant in terms of on-going pregnancy outcomes. PMID:23837065

  12. Modifying the luteal phase support in natural cycle frozen-thawed embryo transfer improves cycle outcome.

    PubMed

    Haas, Jigal; Lantsberg, Daniel; Feldman, Noa; Manela, Daphna; Machtinger, Ronit; Dar, Shir; Rabinovici, Jaron; Orvieto, Raoul

    2015-01-01

    With the recent trend toward single embryo transfer (ET), cryopreservation of extraneous embryos is becoming increasingly prevalent. Several replacement protocols for frozen-thawed ET (FET) exist, with no advantage of one protocol over the others. All consecutive patients undergoing natural cycle Day-3 FET cycles between May 2012 and March 2015 in our IVF unit were evaluated. While following spontaneous ovulation, all patients received progesterone luteal support. Since June 2014, patients underwent the same aforementioned natural cycle FET cycles, with two additional injections, one of recombinant hCG (250 mcg) and the other of GnRH-agonist (triptorelin 0.1 mg), on the day of transfer and 4 d later, respectively. While the patients' clinical characteristics, the prevalence of embryos that survived the thawing process and the number of embryos transferred were comparable between the earlier as compared with the later period, implantation rate, positive β-hCG, clinical, and ongoing pregnancy rates were significantly higher during the later period. We, therefore, suggest that when natural cycle FET is offered, the addition of two injections of recombinant hCG and GnRH-agonist, on the day of transfer and 4 d later, respectively, might increase clinical pregancy rates. Further large prospective studies are needed to elucidate the aforementioned recommendation prior to its routine implementation. PMID:26288149

  13. Luteal Phase Support in assisted reproductive technology treatment: focus on Endometrin(R) (progesterone) vaginal insert.

    PubMed

    Check, Jerome H

    2009-08-01

    Supplementation of progesterone in the luteal phase and continuance of progesterone therapy during the first trimester has been found in several studies to have benefits in promoting fertility, preventing miscarriages and even preventing pre-term labor. Though it can be administered orally, intramuscularly or even sublingually, a very effective route with fewer side effects can be achieved by an intravaginal route. The first vaginal preparations were not made commercially but were compounded by pharmacies. This had the disadvantage of lack of control by the Food and Drug Administration (FDA) ensuring efficacy of the preparations. Furthermore there was a lack of precise dosing leading to batch to batch variation. The first commercially approved vaginal progesterone preparation in the United States was a vaginal gel which has proven very effective. The main side effect was accumulation of a buildup of the vaginal gel sometimes leading to irritation. Natural micronized progesterone for vaginal administration with the brand name of Utrogestan A((R)) had been approved even before the gel in certain European countries. Endometrin((R)) vaginal tablets are the newest natural progesterone approved by the FDA. Comparisons to the vaginal gel and to intramuscular progesterone have shown similar efficacy especially in studies following controlled ovarian hyperstimulation and oocyte egg retrieval and embryo transfer. Larger studies are needed to compare side effects. PMID:19753133

  14. Relationships between insulin-like growth factor-I, milk yield, body condition score, and postpartum luteal activity in high-producing dairy cows.

    PubMed

    Tamadon, Amin; Kafi, Mojtaba; Saeb, Mehdi; Mirzaei, Abdolah; Saeb, Saedeh

    2011-01-01

    The relations between body condition score (BCS), milk yield, serum insulin-like growth factor-I (IGF-I) profile, and luteal activity were investigated in postpartum dairy cows. Seventy-one healthy high-producing multiparous Holstein cows were subjected to transrectal ultrasound scanning twice weekly from the first to the eighth week postpartum. Blood samples were collected twice weekly to measure serum progesterone (P4) and every 2 weeks to detect serum IGF-I concentrations. BCS was monitored weekly after calving. Cows with serum P4 concentrations ≥1 ng/ml on at least two consecutive samplings were considered to have commenced luteal activity. Commencement of luteal activity (C-LA) was observed earlier than 45 days postpartum in 71.8% of cows while 28.2% showed C-LA later than 45 days. Prolonged luteal phase was the most common abnormal pattern of luteal activity observed. Cows with a C-LA earlier than 45 days postpartum had higher (P ≤ 0.05) mean serum concentrations of IGF-I than those with later C-LA. In addition, cows which showed C-LA earlier than 45 days postpartum had more optimal productive indices including shorter calving to conception interval and calving to first service interval (P ≤ 0.05), and fewer services per conception (P = 0.07). C-LA was significantly later in cows that lost more than 0.5 BCS units within 3 weeks postpartum than in those that lost less than 0.5 units BCS during the same interval (P = 0.02). We conclude that high-producing dairy cows with higher postpartum serum IGF-I concentrations have earlier commencement and normal luteal activity, and better reproductive performance. Severity and duration of BCS loss adversely affect commencement of luteal activity.

  15. Social and breed effects on the expression of a PGF2alpha induced oestrus in beef cows.

    PubMed

    Landaeta-Hernández, A J; Palomares-Naveda, R; Soto-Castillo, G; Atencio, A; Chase, C C; Chenoweth, P J

    2004-10-01

    Social organization and breed effects following PGF2alpha were studied in mature Angus, Brahman and Senepol cows allocated into two groups (each A = 5, B = 5 and S = 5). Variables including interval to oestrus onset (IEO), oestrous duration (DE), total mounts received (TMR), and oestrous intensity (IE) were derived via HeatWatch. Breed-type influenced IEO (B = 42.6 +/- 6.7 h; S = 54.6 +/- 6.0 h; and A = 27.8 +/- 5.8 h; p < 0.003). Within breeds, dominant B (69.4 +/- 13.3 h) and S (65.5 +/- 7.4 h) cows were slower (p < 0.05) to be detected in oestrus than subordinate (38.1 +/- 4.4 h) and intermediate (40.6 +/- 6.0 h). However, within A, dominant cows (16.4 +/- 12.5 h) were detected in oestrus earlier (p < 0.05) than intermediate (44.3 +/- 9.2 h) and subordinates (32.7 +/- 5.1 h). Angus (21.5 +/- 2.4 h) and B (22.1 +/- 3.0 h) cows had longer (p < 0.01) DE than S (9.1 +/- 2.8 h). Dominants (20.4 +/- 3.0) and intermediates (20.2 +/- 2.3 h) cows had longer DE (p < 0.04) than subordinates (12.1 +/- 2.1 h) although the interaction breed x social order showed that dominant S had shorter DE than dominant A and B (10.1 +/- 3.3; 34.8 +/- 6.0 h; and 20.0 +/- 6.4 h, respectively; p < 0.001). Angus cows had less TMR than B (p < 0.02) and tended to be less than S cows (p < 0.06). Overall, greatest (p < 0.008) IE occurred in the first 9 h after onset of oestrus with no breed effect (p > 0.05). Dominant cows tended (p < 0.10) to have less TMR (3.2 +/- 0.7 mounts) than subordinate (4.1 +/- 0.4 mounts) and intermediate (4.7 +/- 0.6 mounts) throughout, especially 3-6 h after oestrus onset (p < 0.07). Breed and social order both influence PGF2alpha-induced oestrus behaviour. PMID:15367263

  16. Tumor necrosis factor-alpha induced expression of matrix metalloproteinase-9 through p21-activated Kinase-1

    PubMed Central

    Zhou, Ling; Yan, Chunli; Gieling, Roben G; Kida, Yujiro; Garner, Warren; Li, Wei; Han, Yuan-Ping

    2009-01-01

    Background Expressed in embryonic development, matrix metalloprotein-9 (MMP-9) is absent in most of developed adult tissues, but recurs in inflammation during tissue injury, wound healing, tumor formation and metastasis. Expression of MMP-9 is tightly controlled by extracellular cues including pro-inflammatory cytokines and extracellular matrix (ECM). While the pathologic functions of MMP-9 are evident, the intracellular signaling pathways to control its expression are not fully understood. In this study we investigated mechanism of cytokine induced MMP-9 with particular emphasis on the role of p21-activated-kinase-1 (PAK1) and the down stream signaling. Results In response to TNF-alpha or IL-1alpha, PAK1 was promptly activated, as characterized by a sequential phosphorylation, initiated at threonine-212 followed by at threonine-423 in the activation loop of the kinase, in human skin keratinocytes, dermal fibroblasts, and rat hepatic stellate cells. Ectopic expression of PAK1 variants, but not p38 MAP kinase, impaired the TNF-alpha-induced MMP-9 expression, while other MMPs such as MMP-2, -3 and -14 were not affected. Activation of Jun N-terminal kinase (JNK) and NF-kappaB has been demonstrated to be essential for MMP-9 expression. Expression of inactive PAK1 variants impaired JNK but not NF-kappaB activation, which consequently suppressed the 5'-promoter activities of the MMP-9 gene. After the cytokine-induced phosphorylation, both ectopically expressed and endogenous PAK1 proteins were promptly accumulated even in the condition of suppressing protein synthesis, suggesting the PAK1 protein is stabilized upon TNF-alpha stimulation. Stabilization of PAK1 protein by TNF-alpha treatment is independent of the kinase catalytic activity and p21 GTPase binding capacities. In contrast to epithelial cells, mesenchymal cells require 3-dimensional type-I collagen in response to TNF-alpha to massively express MMP-9. The collagen effect is mediated, in part, by boost JNK

  17. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx.

    PubMed

    Amelkina, Olga; Zschockelt, Lina; Painer, Johanna; Serra, Rodrigo; Villaespesa, Francisco; Braun, Beate C; Jewgenow, Katarina

    2015-01-01

    The corpus luteum (CL) is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2) and pro-apoptotic BCL2-associated X protein (BAX), the executioner caspase-3 (CASP3), as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF) and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B). We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL) and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  18. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx.

    PubMed

    Amelkina, Olga; Zschockelt, Lina; Painer, Johanna; Serra, Rodrigo; Villaespesa, Francisco; Braun, Beate C; Jewgenow, Katarina

    2015-01-01

    The corpus luteum (CL) is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2) and pro-apoptotic BCL2-associated X protein (BAX), the executioner caspase-3 (CASP3), as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF) and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B). We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL) and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  19. Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx

    PubMed Central

    Amelkina, Olga; Zschockelt, Lina; Painer, Johanna; Serra, Rodrigo; Villaespesa, Francisco; Braun, Beate C.; Jewgenow, Katarina

    2015-01-01

    The corpus luteum (CL) is a transient gland formed in the ovary after ovulation and is the major source of progesterone. In the Iberian and Eurasian lynx, CL physiologically persist after parturition and retain their capacity to produce progesterone, thus suppressing the ovarian activity. This unique reproductive characteristic has a big impact on the success of assisted reproduction techniques in the endangered Iberian lynx. The mechanisms behind CL persistence are not yet understood and require extensive studies on potential luteotropic and luteolytic factors in felids. Because the apoptosis system has been shown to be involved in structural regression of CL in many species, we aimed to investigate the capacity of perCL to undergo apoptosis. In addition, we performed initial studies on the apoptosis system in the luteal phase of the domestic cat. No previous research on this system has been made in this species. Our factors of interest included agents of the intrinsic apoptosis pathway, i.e., pro-survival B-cell CLL/lymphoma 2 (BCL2) and pro-apoptotic BCL2-associated X protein (BAX), the executioner caspase-3 (CASP3), as well as of the extrinsic pathway, i.e., pro-apoptotic receptor FAS, and tumor necrosis factor (TNF) and its receptors (pro-apoptotic TNFRSF1A and pro-survival TNFRSF1B). We analyzed the relative mRNA levels of these factors, as well as protein localization of CASP3 and TNF during stages of pregnancy and the non-pregnant luteal phase in CL of domestic cats. The same factors were investigated in freshly ovulated CL (frCL) and perCL of Iberian and Eurasian lynx, which were histologically analyzed. All factors were present in the CL tissue of both domestic cat and lynx throughout all analyzed stages. The presence of pro-apoptotic factors BAX, CASP3, FAS and TNFRSF1A in perCL of the Eurasian and Iberian lynx might indicate the potential sensitivity of perCL to apoptotic signals. The expression of pro-survival factors BCL2 and TNFRSF1B was

  20. Improved Regression Calibration

    ERIC Educational Resources Information Center

    Skrondal, Anders; Kuha, Jouni

    2012-01-01

    The likelihood for generalized linear models with covariate measurement error cannot in general be expressed in closed form, which makes maximum likelihood estimation taxing. A popular alternative is regression calibration which is computationally efficient at the cost of inconsistent estimation. We propose an improved regression calibration…

  1. Prediction in Multiple Regression.

    ERIC Educational Resources Information Center

    Osborne, Jason W.

    2000-01-01

    Presents the concept of prediction via multiple regression (MR) and discusses the assumptions underlying multiple regression analyses. Also discusses shrinkage, cross-validation, and double cross-validation of prediction equations and describes how to calculate confidence intervals around individual predictions. (SLD)

  2. Morse–Smale Regression

    SciTech Connect

    Gerber, Samuel; Rubel, Oliver; Bremer, Peer -Timo; Pascucci, Valerio; Whitaker, Ross T.

    2012-01-19

    This paper introduces a novel partition-based regression approach that incorporates topological information. Partition-based regression typically introduces a quality-of-fit-driven decomposition of the domain. The emphasis in this work is on a topologically meaningful segmentation. Thus, the proposed regression approach is based on a segmentation induced by a discrete approximation of the Morse–Smale complex. This yields a segmentation with partitions corresponding to regions of the function with a single minimum and maximum that are often well approximated by a linear model. This approach yields regression models that are amenable to interpretation and have good predictive capacity. Typically, regression estimates are quantified by their geometrical accuracy. For the proposed regression, an important aspect is the quality of the segmentation itself. Thus, this article introduces a new criterion that measures the topological accuracy of the estimate. The topological accuracy provides a complementary measure to the classical geometrical error measures and is very sensitive to overfitting. The Morse–Smale regression is compared to state-of-the-art approaches in terms of geometry and topology and yields comparable or improved fits in many cases. Finally, a detailed study on climate-simulation data demonstrates the application of the Morse–Smale regression. Supplementary Materials are available online and contain an implementation of the proposed approach in the R package msr, an analysis and simulations on the stability of the Morse–Smale complex approximation, and additional tables for the climate-simulation study.

  3. Premenstrual Dysphoria and Luteal Stress in Dominant-Social-Status Female Macaques

    PubMed Central

    Qiao, Mingqi; Zhao, Qitao; Wei, Sheng; Zhang, Huiyun; Wang, Haijun

    2013-01-01

    The current study aims to extend our previous work to develop nonhuman primate model for prospectively studying the mechanism underlying premenstrual dysphoric disorder (PMDD). Thirty young dominant-status female monkeys were randomly divided into the control group, the model group, and JQP group. For two consecutive menstrual cycles, from day 18 to 22, monkeys in the model and JQP groups were housed and immobilized singly in specially designed isolation cages for 5-6 hours per day. At the same time, the pharmaceutical interference effect of jingqianping (JQP) granule, a traditional Chinese medicine specifically used to cure PMDD patients, was tested using monkeys in the JQP group. The behavior and facial expressions of monkeys were photographed with an automatic vidicon and were quantitatively analyzed by “the emotion evaluation scale of female experimental macaque.” Changes in serum level of progesterone and estradiol were measured with RIA, and serum level of 5-HT, noradrenaline, and dopamine were measured with HPLC. After experiencing mentioned above stress, 70% of monkeys of model group showed PMDD symptoms during three consecutive menstrual cycles. Estradiol and progesterone serum level decreased (P < 0.01). Moreover, the peak value of secreted hormones in their follicular phase did not occur. Serum level of 5-HT and dopamine were significantly lower (P < 0.01), but the serum noradrenaline level was higher (P < 0.01). Moreover, in monkeys administered by JQP granule, both PMDD symptoms and the anormal serum level of neurotransmitters could be obviously reversed. This special luteal-phase treatment on dominant-social-status monkeys might be a feasible way to create models mimicking PMDD. PMID:24371458

  4. Comparison of Follicular and Luteal Phase Mucosal Markers of HIV Susceptibility in Healthy Women.

    PubMed

    Thurman, Andrea Ries; Chandra, Neelima; Yousefieh, Nazita; Zalenskaya, Irina; Kimble, Thomas; Asin, Susana; Rollenhagen, Christiane; Anderson, Sharon M; Herold, Betsy; Mesquita, Pedro M M; Richardson-Harman, Nicola; Cunningham, Tina; Schwartz, Jill L; Doncel, Gustavo F

    2016-06-01

    The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, antimicrobial activity of the cervicovaginal (CV) lavage (CVL), vaginal flora, and p24 antigen production from CV tissues after ex vivo human immunodeficiency virus (HIV) infection between follicular (FOL) and luteal (LUT) phases of the menstrual cycle. CV tissue biopsies, CV secretions, and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV-seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 and Escherichia coli by the CVL, vaginal pH or Nugent score, or production of p24 antigen after ex vivo infection by HIV-1BaL between CV samples obtained in the FOL phase versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials. PMID:26750085

  5. Premenstrual dysphoria and luteal stress in dominant-social-status female macaques.

    PubMed

    Qiao, Mingqi; Zhao, Qitao; Wei, Sheng; Zhang, Huiyun; Wang, Haijun

    2013-01-01

    The current study aims to extend our previous work to develop nonhuman primate model for prospectively studying the mechanism underlying premenstrual dysphoric disorder (PMDD). Thirty young dominant-status female monkeys were randomly divided into the control group, the model group, and JQP group. For two consecutive menstrual cycles, from day 18 to 22, monkeys in the model and JQP groups were housed and immobilized singly in specially designed isolation cages for 5-6 hours per day. At the same time, the pharmaceutical interference effect of jingqianping (JQP) granule, a traditional Chinese medicine specifically used to cure PMDD patients, was tested using monkeys in the JQP group. The behavior and facial expressions of monkeys were photographed with an automatic vidicon and were quantitatively analyzed by "the emotion evaluation scale of female experimental macaque." Changes in serum level of progesterone and estradiol were measured with RIA, and serum level of 5-HT, noradrenaline, and dopamine were measured with HPLC. After experiencing mentioned above stress, 70% of monkeys of model group showed PMDD symptoms during three consecutive menstrual cycles. Estradiol and progesterone serum level decreased (P < 0.01). Moreover, the peak value of secreted hormones in their follicular phase did not occur. Serum level of 5-HT and dopamine were significantly lower (P < 0.01), but the serum noradrenaline level was higher (P < 0.01). Moreover, in monkeys administered by JQP granule, both PMDD symptoms and the anormal serum level of neurotransmitters could be obviously reversed. This special luteal-phase treatment on dominant-social-status monkeys might be a feasible way to create models mimicking PMDD. PMID:24371458

  6. Stimulatory effect of luteinizing hormone, insulin-like growth factor-1, and epidermal growth factor on vascular endothelial growth factor production in cultured bubaline luteal cells.

    PubMed

    Chouhan, V S; Dangi, S S; Babitha, V; Verma, M R; Bag, S; Singh, G; Sarkar, M

    2015-10-15

    The purpose of this study was to evaluate the temporal (24, 48, and 72 hours) and dose-dependent (0, 5, 10, and 100 ng/mL of LH, insulin-like growth factor 1 [IGF-1], and EGF) in vitro expression and secretion patterns of vascular endothelial growth factor (VEGF) in luteal cell culture during different stages of estrous cycle in water buffaloes. Corpus luteum samples from ovaries of early luteal phase (ELP; Days 1-4), midluteal phase (Days 5-10), and late luteal phase (Days 11-16) were collected from a local slaughterhouse. The samples were then processed and cultured in (serum containing) appropriate cell culture medium and incubated separately with three factors (LH, IGF-1, or EGF) at the previously mentioned three dose-duration combinations. At the end of the respective incubation periods, VEGF was assayed in the spent culture medium by ELISA, whereas the cultured cells were used for VEGF mRNA expression by quantitative real-time polymerase chain reaction. The results of the present study disclosed dose- and time-dependent stimulatory effects of LH, IGF-1, and EGF on VEGF production in bubaline luteal cells. The VEGF expression and secretion from the cultured luteal cells were highest during the ELP, intermediate in the midluteal phase, and lowest in the late luteal phase of the estrous cycle for all the three tested factors. Comparison of the results of the three treatments depicted EGF as the most potent stimulating factor followed by IGF-1 and LH. Immunocytochemistry findings in luteal cell culture of ELP agreed with the VEGF expression and secretion. In conclusion, mRNA expression, protein secretion, and immunolocalization of VEGF data clearly indicated for the first time that LH, IGF-1, and EGF play an important role in stimulating luteal angiogenesis in buffalo CL. The highest expression and secretion of VEGF in the ELP might be associated with the development of blood vessels in early growth of CL, which in turn gets augmented by the aforementioned

  7. Stimulatory effect of luteinizing hormone, insulin-like growth factor-1, and epidermal growth factor on vascular endothelial growth factor production in cultured bubaline luteal cells.

    PubMed

    Chouhan, V S; Dangi, S S; Babitha, V; Verma, M R; Bag, S; Singh, G; Sarkar, M

    2015-10-15

    The purpose of this study was to evaluate the temporal (24, 48, and 72 hours) and dose-dependent (0, 5, 10, and 100 ng/mL of LH, insulin-like growth factor 1 [IGF-1], and EGF) in vitro expression and secretion patterns of vascular endothelial growth factor (VEGF) in luteal cell culture during different stages of estrous cycle in water buffaloes. Corpus luteum samples from ovaries of early luteal phase (ELP; Days 1-4), midluteal phase (Days 5-10), and late luteal phase (Days 11-16) were collected from a local slaughterhouse. The samples were then processed and cultured in (serum containing) appropriate cell culture medium and incubated separately with three factors (LH, IGF-1, or EGF) at the previously mentioned three dose-duration combinations. At the end of the respective incubation periods, VEGF was assayed in the spent culture medium by ELISA, whereas the cultured cells were used for VEGF mRNA expression by quantitative real-time polymerase chain reaction. The results of the present study disclosed dose- and time-dependent stimulatory effects of LH, IGF-1, and EGF on VEGF production in bubaline luteal cells. The VEGF expression and secretion from the cultured luteal cells were highest during the ELP, intermediate in the midluteal phase, and lowest in the late luteal phase of the estrous cycle for all the three tested factors. Comparison of the results of the three treatments depicted EGF as the most potent stimulating factor followed by IGF-1 and LH. Immunocytochemistry findings in luteal cell culture of ELP agreed with the VEGF expression and secretion. In conclusion, mRNA expression, protein secretion, and immunolocalization of VEGF data clearly indicated for the first time that LH, IGF-1, and EGF play an important role in stimulating luteal angiogenesis in buffalo CL. The highest expression and secretion of VEGF in the ELP might be associated with the development of blood vessels in early growth of CL, which in turn gets augmented by the aforementioned

  8. Regression problems for magnitudes

    NASA Astrophysics Data System (ADS)

    Castellaro, S.; Mulargia, F.; Kagan, Y. Y.

    2006-06-01

    Least-squares linear regression is so popular that it is sometimes applied without checking whether its basic requirements are satisfied. In particular, in studying earthquake phenomena, the conditions (a) that the uncertainty on the independent variable is at least one order of magnitude smaller than the one on the dependent variable, (b) that both data and uncertainties are normally distributed and (c) that residuals are constant are at times disregarded. This may easily lead to wrong results. As an alternative to least squares, when the ratio between errors on the independent and the dependent variable can be estimated, orthogonal regression can be applied. We test the performance of orthogonal regression in its general form against Gaussian and non-Gaussian data and error distributions and compare it with standard least-square regression. General orthogonal regression is found to be superior or equal to the standard least squares in all the cases investigated and its use is recommended. We also compare the performance of orthogonal regression versus standard regression when, as often happens in the literature, the ratio between errors on the independent and the dependent variables cannot be estimated and is arbitrarily set to 1. We apply these results to magnitude scale conversion, which is a common problem in seismology, with important implications in seismic hazard evaluation, and analyse it through specific tests. Our analysis concludes that the commonly used standard regression may induce systematic errors in magnitude conversion as high as 0.3-0.4, and, even more importantly, this can introduce apparent catalogue incompleteness, as well as a heavy bias in estimates of the slope of the frequency-magnitude distributions. All this can be avoided by using the general orthogonal regression in magnitude conversions.

  9. A selective estrogen receptor modulator inhibits TNF-alpha-induced apoptosis by activating ERK1/2 signaling pathway in vascular endothelial cells.

    PubMed

    Yu, Jing; Eto, Masato; Akishita, Masahiro; Okabe, Tetsuro; Ouchi, Yasuyoshi

    2009-07-01

    Tumor necrosis factor (TNF-alpha) is a pleiotropic cytokine exerting both inflammatory and cell death activity and is thought to play a role in the pathogenesis of atherosclerosis. The present study was designed to examine whether the raloxifene analogue, LY117018 could inhibit TNF-alpha-induced apoptosis in vascular endothelial cells and to clarify the involved mechanisms. Apoptosis of endothelial cells was determined by DNA fragmentation assay and the activation of caspase-3. LY117018 significantly inhibited TNF-alpha-induced caspase-3 activation and cell DNA fragmentation levels in bovine carotid artery endothelial cells. The inhibitory effect of LY117018 was abolished by an estrogen receptor antagonist ICI 182,780. p38 MAPK, JNK, ERK1/2 and Akt have been shown to act as apoptotic or anti-apoptotic signals. TNF-alpha stimulated the phosphorylation levels of p38 MAPK, JNK, ERK1/2 and Akt in vascular endothelial cells. TNF-alpha-induced apoptosis was significantly decreased by SB203580, a p38 MAPK inhibitor or SP600125, a JNK inhibitor, but was enhanced by an ERK1/2 pathway inhibitor, PD98059 or a PI3-kinase/Akt pathway inhibitor, wortmannin. The anti-apoptotic effect of LY117018 was abrogated only by PD98059 but was not affected by the inhibitors for p38 MAPK, JNK, or Akt. LY117018 stimulated the further increase in phosphorylation of ERK1/2 in TNF-alpha treated endothelial cells but it did not affect phosphorylation levels of p38 MAPK, JNK or Akt. These results suggest that LY 110718 prevents caspase-3 dependent apoptosis induced by TNF-alpha in vascular endothelial cells through activation of the estrogen receptors and the ERK1/2 signaling pathway. PMID:19275968

  10. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

    2015-02-01

    Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments. PMID:25715250

  11. Transcriptional Profiling of Human Endocervical Tissues Reveals Distinct Gene Expression in the Follicular and Luteal Phases of the Menstrual Cycle.

    PubMed

    Yildiz-Arslan, Sevim; Coon, John S; Hope, Thomas J; Kim, J Julie

    2016-06-01

    The endocervix plays an important role in providing appropriate protective mechanisms of the upper female reproductive tract (FRT) while at the same time providing the appropriate milieu for sperm transport. Hormone fluctuations throughout the menstrual cycle contribute to changes in the mucosal environment that render the FRT vulnerable to infectious diseases. The objective of this study was to identify genes in human endocervix tissues that were differentially expressed in the follicular versus the luteal phases of the menstrual cycle using gene expression profiling. A microarray using the IIlumina platform was performed with eight endocervix tissues from follicular and four tissues from luteal phases of the menstrual cycle. Data analysis revealed significant differential expression of 110 genes between the two phases, with a P value <0.05 and a fold change cutoff of 1.5. Categorization of these genes, using Ingenuity Pathway Analysis, MetaCore from Thomson Reuters, and DAVID, revealed genes associated with extracellular matrix remodeling and cell-matrix interactions, amino acid metabolism, and lipid metabolism, as well as immune regulation in the follicular phase tissues. In luteal phase tissues, genes associated with chromatin remodeling, inflammation, angiogenesis, oxidative stress, and immune cell regulation were predominately expressed. Using samples from additional patients' tissues, select genes were confirmed by quantitative real-time PCR; immunohistochemical staining was also done to examine protein levels. This is the first microarray analysis comparing gene expression in endocervix tissues in cycling women. This study identified key genes and molecular pathways that were differentially regulated during the menstrual cycle. PMID:27170437

  12. Estrogen supplementation to progesterone as luteal phase support in patients undergoing in vitro fertilization: systematic review and meta-analysis.

    PubMed

    Zhang, Xiao-Mei; Lv, Fang; Wang, Pin; Huang, Xia-Man; Liu, Kai-Feng; Pan, Yu; Dong, Nai-Jun; Ji, Yu-Rong; She, Hong; Hu, Rong

    2015-02-01

    Meta-analyses have found conflicting results with respect to the use of progesterone or progesterone plus estrogen as luteal phase support for in vitro fertilization (IVF) protocols involving gonadotropins and/or gonadotropin-releasing hormone analogs. The aim of the present study was to perform an updated meta-analysis on the efficacy of progesterone versus progesterone plus estrogen as luteal phase support. We searched the MEDLINE, Cochrane Library, and Google Scholar databases (up to March 18, 2014). The search terms were (estrogen OR estradiol OR oestradiol) AND (progesterone) AND (IVF OR in vitro fertilization) AND (randomized OR prospective). We did not limit the form of estrogen and included subjects who contributed more than 1 cycle to a study. The primary outcome was clinical pregnancy rate. Secondary outcomes were ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate. A total of 11 articles were included in the present analysis, with variable numbers of studies assessing each outcome measure. Results of statistical analyses indicated that progesterone plus estrogen treatment was more likely to result in clinical pregnancy than progesterone alone (pooled odds ratio 1.617, 95% confidence interval 1.059-2.471; P = 0.026). No significant difference between the 2 treatment regimens was found for the other outcome measures. Progesterone plus estrogen for luteal phase support is associated with a higher clinical pregnancy rate than progesterone alone in women undergoing IVF, but other outcomes such as ongoing pregnancy rate, fertilization rate, implantation rate, and miscarriage rate are the same for both treatments.

  13. Ochnaflavone inhibits TNF-alpha-induced human VSMC proliferation via regulation of cell cycle, ERK1/2, and MMP-9.

    PubMed

    Suh, Seok-Jong; Jin, Un-Ho; Kim, Sung-Hoon; Chang, Hyeun-Wook; Son, Jong-Keun; Lee, Seung Ho; Son, Kun-Ho; Kim, Cheorl-Ho

    2006-12-01

    Ochnaflavone (c-3 of apigenin-0-c-4 of apigenin; OC), a biflavonoid present in the human diet, is known to inhibit angiotensin II-induced hypertrophy and serum-induced smooth muscle cell proliferation. OC is known to have anti-fungal and anti-inflammatory activities. However, it is not known whether OC exerts similar cardioprotective effects in cells treated with tumor necrosis factor (TNF)-alpha. In this study, we isolated OC from Lonicera japonica and studied its effect on matrix metalloproteinase-9 (MMP-9) gene expression in human aortic smooth muscle cells (HASMC). Furthermore, we investigated whether OC exerts the multiple suppressive effects on cytokine TNF-alpha-induced HASMC. Treatment of OC showed its potent inhibitory effects on DNA synthesis of cultured HASMC in the presence of TNF-alpha. These inhibitory effects were associated with reduced extracellular signal-regulated kinase 1/2 (ERK1/2) activity and G1 cell cycle arrest. Treatment of OC, which induced a cell cycle block in G1-phase, induced downregulation of cyclins and CDKs and upregulation of the CDK inhibitor p21(waf1) expression, whereas upregulation of p27 or p53 by OC was not observed. Because anti-atherogenic effects need not be limited to anti-proliferation, we decided to examine whether OC exerts inhibitory effects on MMP-9 activity in TNF-alpha-induced HASMC. OC inhibited TNF-alpha-induced MMP-9 secretion on HASMC in a dose-dependent manner. This inhibition was characterized by downregulation of MMP-9, which was transcriptionally regulated at nuclear factor (NF)-kappaB site and activation protein (AP)-1 site in the MMP-9 promoter. These findings indicate the efficacy of OC in inhibiting cell proliferation, G1 to S-phase cell cycle progress, and MMP-9 expression through the transcription factors NF-kappaB and AP-1 on TNF-alpha-induced HASMC. The findings of the present study may provide a potential mechanism that explains the anti-atherogenic activity of OC.

  14. Multivariate Regression with Calibration*

    PubMed Central

    Liu, Han; Wang, Lie; Zhao, Tuo

    2014-01-01

    We propose a new method named calibrated multivariate regression (CMR) for fitting high dimensional multivariate regression models. Compared to existing methods, CMR calibrates the regularization for each regression task with respect to its noise level so that it is simultaneously tuning insensitive and achieves an improved finite-sample performance. Computationally, we develop an efficient smoothed proximal gradient algorithm which has a worst-case iteration complexity O(1/ε), where ε is a pre-specified numerical accuracy. Theoretically, we prove that CMR achieves the optimal rate of convergence in parameter estimation. We illustrate the usefulness of CMR by thorough numerical simulations and show that CMR consistently outperforms other high dimensional multivariate regression methods. We also apply CMR on a brain activity prediction problem and find that CMR is as competitive as the handcrafted model created by human experts. PMID:25620861

  15. Metamorphic geodesic regression.

    PubMed

    Hong, Yi; Joshi, Sarang; Sanchez, Mar; Styner, Martin; Niethammer, Marc

    2012-01-01

    We propose a metamorphic geodesic regression approach approximating spatial transformations for image time-series while simultaneously accounting for intensity changes. Such changes occur for example in magnetic resonance imaging (MRI) studies of the developing brain due to myelination. To simplify computations we propose an approximate metamorphic geodesic regression formulation that only requires pairwise computations of image metamorphoses. The approximated solution is an appropriately weighted average of initial momenta. To obtain initial momenta reliably, we develop a shooting method for image metamorphosis.

  16. Relation between progesterone concentrations during the early luteal phase and follicular dynamics in goats.

    PubMed

    Menchaca, Alejo; Rubianes, Edgardo

    2002-03-15

    We studied the relationship between progesterone (P4) concentrations early in the estrus cycle and follicular dynamics in dairy goats. We used seven untreated goats (control group) and six progesterone treated goats (P group) with a controlled internal drug release device from Days 0 to 5 (Day 0: day of ovulation). We performed daily ultrasonograph during the interovulatory interval to determine ovarian change and took daily blood samples to determine serum estradiol 17beta (E2) and P4 concentrations by RIA. We divided the control goats into 3- (n = 4) and 4-wave goats (n = 3), according to the number of follicular waves recorded during the ovulatory cycle. Mean progesterone concentrations between Days I and 5 were higher and mean estradiol concentrations between Days 3 and 5 were lower in 4-wave goats (P4: 3.8+/-0.2 ng/ml; E2: 1.6+/-0.2 pg/ml) than in 3-wave goats (P4: 2.0+/-0.5 ng/ml, P < 0.05; E2: 4.4+/-0.9 pg/ml, P < 0.05). Wave 2 emerged earlier in 4-wave (Day 4.2+/-0.3) than in 3-wave goats (Day 7.3+/-0.3, P < 0.05). Three out of six of the progesterone-treated goats had short cycles (mean 8.0+/-0.0 days) and ovulated from Wave 1. The other three goats had shorter cycles (mean 18.3+/-0.3 days) than the control group (20.0+/-0.2 days; P < 0.05), although they were within the normal range of control cycles (shortened cycles). In the three treated goats with shortened cycles (two with four waves, one with three waves), mean progesterone concentrations between Days I and 5 were higher (4.7+/-0.6 ng/ml) than in the 3-wave control goats. In these goats, Wave 2 emerged at Day 4.3+/-0.3, similar to the time observed in 4-wave goats but earlier (P < or = 0.05) than in 3-wave control goats. Overall results confirm a relationship between the progesterone levels and the follicular wave turnover during the early luteal phase in the goat. Higher progesterone concentrations may accelerate follicular turnover probably by an early decline of the negative feedback action of

  17. Effects of intraluteal implants of prostaglandin E1 or E2 on angiogenic growth factors in luteal tissue of Angus and Brahman cows.

    PubMed

    Weems, Yoshie S; Ma, Yan; Ford, Stephen P; Nett, Terry M; Vann, Rhonda C; Lewis, Andrew W; Neuendorff, Don A; Welsh, Thomas H; Randel, Ronald D; Weems, Charles W

    2014-12-01

    Previously, it was reported that intraluteal implants containing prostaglandin E1 or E2 (PGE1 and PGE2) in Angus or Brahman cows prevented luteolysis by preventing loss of mRNA expression for luteal LH receptors and luteal unoccupied and occupied LH receptors. In addition, intraluteal implants containing PGE1 or PGE2 upregulated mRNA expression for FP prostanoid receptors and downregulated mRNA expression for EP2 and EP4 prostanoid receptors. Luteal weight during the estrous cycle of Brahman cows was reported to be lesser than that of Angus cows but not during pregnancy. The objective of this experiment was to determine whether intraluteal implants containing PGE1 or PGE2 alter vascular endothelial growth factor (VEGF), fibroblast growth factor-2 (FGF-2), angiopoietin-1 (ANG-1), and angiopoietin-2 (ANG-2) protein in Brahman or Angus cows. On Day 13 of the estrous cycle, Angus cows received no intraluteal implant and corpora lutea were retrieved, or Angus and Brahman cows received intraluteal silastic implants containing vehicle, PGE1, or PGE2 on Day 13 and corpora lutea were retrieved on Day 19. Corpora lutea slices were analyzed for VEGF, FGF-2, ANG-1, and ANG-2 angiogenic proteins via Western blot. Day-13 Angus cow luteal tissue served as preluteolytic controls. Data for VEGF were not affected (P > 0.05) by day, breed, or treatment. PGE1 or PGE2 increased (P < 0.05) FGF-2 in luteal tissue of Angus cows compared with Day-13 and Day-19 Angus controls but decreased (P < 0.05) FGF-2 in luteal tissue of Brahman cows when compared w Day-13 or Day-19 Angus controls. There was no effect (P > 0.05) of PGE1 or PGE2 on ANG-1 in Angus luteal tissue when compared with Day-13 or Day-19 controls, but ANG-1 was decreased (P < 0.05) by PGE1 or PGE2 in Brahman cows when compared with Day-19 Brahman controls. ANG-2 was increased (P < 0.05) on Day 19 in Angus Vehicle controls when compared with Day-13 Angus controls, which was prevented (P < 0.05) by PGE1 but not by PGE2 in Angus

  18. Temperature dependence of alpha-induced scintillation in the 1,1,4,4-tetraphenyl-1,3-butadiene wavelength shifter

    NASA Astrophysics Data System (ADS)

    Veloce, L. M.; Kuźniak, M.; Di Stefano, P. C. F.; Noble, A. J.; Boulay, M. G.; Nadeau, P.; Pollmann, T.; Clark, M.; Piquemal, M.; Schreiner, K.

    2016-06-01

    Liquid noble based particle detectors often use the organic wavelength shifter 1,1,4,4-tetraphenyl-1,3-butadiene (TPB) which shifts UV scintillation light to the visible regime, facilitating its detection, but which also can scintillate on its own. Dark matter searches based on this type of detector commonly rely on pulse-shape discrimination (PSD) for background mitigation. Alpha-induced scintillation therefore represents a possible background source in dark matter searches. The timing characteristics of this scintillation determine whether this background can be mitigated through PSD. We have therefore characterized the pulse shape and light yield of alpha induced TPB scintillation at temperatures ranging from 300 K down to 4 K, with special attention given to liquid noble gas temperatures. We find that the pulse shapes and light yield depend strongly on temperature. In addition, the significant contribution of long time constants above ~50 K provides an avenue for discrimination between alpha decay events in TPB and nuclear-recoil events in noble liquid detectors.

  19. Latent Regression Analysis.

    PubMed

    Tarpey, Thaddeus; Petkova, Eva

    2010-07-01

    Finite mixture models have come to play a very prominent role in modelling data. The finite mixture model is predicated on the assumption that distinct latent groups exist in the population. The finite mixture model therefore is based on a categorical latent variable that distinguishes the different groups. Often in practice distinct sub-populations do not actually exist. For example, disease severity (e.g. depression) may vary continuously and therefore, a distinction of diseased and not-diseased may not be based on the existence of distinct sub-populations. Thus, what is needed is a generalization of the finite mixture's discrete latent predictor to a continuous latent predictor. We cast the finite mixture model as a regression model with a latent Bernoulli predictor. A latent regression model is proposed by replacing the discrete Bernoulli predictor by a continuous latent predictor with a beta distribution. Motivation for the latent regression model arises from applications where distinct latent classes do not exist, but instead individuals vary according to a continuous latent variable. The shapes of the beta density are very flexible and can approximate the discrete Bernoulli distribution. Examples and a simulation are provided to illustrate the latent regression model. In particular, the latent regression model is used to model placebo effect among drug treated subjects in a depression study. PMID:20625443

  20. Semiparametric Regression Pursuit.

    PubMed

    Huang, Jian; Wei, Fengrong; Ma, Shuangge

    2012-10-01

    The semiparametric partially linear model allows flexible modeling of covariate effects on the response variable in regression. It combines the flexibility of nonparametric regression and parsimony of linear regression. The most important assumption in the existing methods for the estimation in this model is to assume a priori that it is known which covariates have a linear effect and which do not. However, in applied work, this is rarely known in advance. We consider the problem of estimation in the partially linear models without assuming a priori which covariates have linear effects. We propose a semiparametric regression pursuit method for identifying the covariates with a linear effect. Our proposed method is a penalized regression approach using a group minimax concave penalty. Under suitable conditions we show that the proposed approach is model-pursuit consistent, meaning that it can correctly determine which covariates have a linear effect and which do not with high probability. The performance of the proposed method is evaluated using simulation studies, which support our theoretical results. A real data example is used to illustrated the application of the proposed method. PMID:23559831

  1. [Understanding logistic regression].

    PubMed

    El Sanharawi, M; Naudet, F

    2013-10-01

    Logistic regression is one of the most common multivariate analysis models utilized in epidemiology. It allows the measurement of the association between the occurrence of an event (qualitative dependent variable) and factors susceptible to influence it (explicative variables). The choice of explicative variables that should be included in the logistic regression model is based on prior knowledge of the disease physiopathology and the statistical association between the variable and the event, as measured by the odds ratio. The main steps for the procedure, the conditions of application, and the essential tools for its interpretation are discussed concisely. We also discuss the importance of the choice of variables that must be included and retained in the regression model in order to avoid the omission of important confounding factors. Finally, by way of illustration, we provide an example from the literature, which should help the reader test his or her knowledge.

  2. Practical Session: Logistic Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    An exercise is proposed to illustrate the logistic regression. One investigates the different risk factors in the apparition of coronary heart disease. It has been proposed in Chapter 5 of the book of D.G. Kleinbaum and M. Klein, "Logistic Regression", Statistics for Biology and Health, Springer Science Business Media, LLC (2010) and also by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr341.pdf). This example is based on data given in the file evans.txt coming from http://www.sph.emory.edu/dkleinb/logreg3.htm#data.

  3. Explorations in Statistics: Regression

    ERIC Educational Resources Information Center

    Curran-Everett, Douglas

    2011-01-01

    Learning about statistics is a lot like learning about science: the learning is more meaningful if you can actively explore. This seventh installment of "Explorations in Statistics" explores regression, a technique that estimates the nature of the relationship between two things for which we may only surmise a mechanistic or predictive connection.…

  4. Modern Regression Discontinuity Analysis

    ERIC Educational Resources Information Center

    Bloom, Howard S.

    2012-01-01

    This article provides a detailed discussion of the theory and practice of modern regression discontinuity (RD) analysis for estimating the effects of interventions or treatments. Part 1 briefly chronicles the history of RD analysis and summarizes its past applications. Part 2 explains how in theory an RD analysis can identify an average effect of…

  5. Multiple linear regression analysis

    NASA Technical Reports Server (NTRS)

    Edwards, T. R.

    1980-01-01

    Program rapidly selects best-suited set of coefficients. User supplies only vectors of independent and dependent data and specifies confidence level required. Program uses stepwise statistical procedure for relating minimal set of variables to set of observations; final regression contains only most statistically significant coefficients. Program is written in FORTRAN IV for batch execution and has been implemented on NOVA 1200.

  6. Mechanisms of neuroblastoma regression

    PubMed Central

    Brodeur, Garrett M.; Bagatell, Rochelle

    2014-01-01

    Recent genomic and biological studies of neuroblastoma have shed light on the dramatic heterogeneity in the clinical behaviour of this disease, which spans from spontaneous regression or differentiation in some patients, to relentless disease progression in others, despite intensive multimodality therapy. This evidence also suggests several possible mechanisms to explain the phenomena of spontaneous regression in neuroblastomas, including neurotrophin deprivation, humoral or cellular immunity, loss of telomerase activity and alterations in epigenetic regulation. A better understanding of the mechanisms of spontaneous regression might help to identify optimal therapeutic approaches for patients with these tumours. Currently, the most druggable mechanism is the delayed activation of developmentally programmed cell death regulated by the tropomyosin receptor kinase A pathway. Indeed, targeted therapy aimed at inhibiting neurotrophin receptors might be used in lieu of conventional chemotherapy or radiation in infants with biologically favourable tumours that require treatment. Alternative approaches consist of breaking immune tolerance to tumour antigens or activating neurotrophin receptor pathways to induce neuronal differentiation. These approaches are likely to be most effective against biologically favourable tumours, but they might also provide insights into treatment of biologically unfavourable tumours. We describe the different mechanisms of spontaneous neuroblastoma regression and the consequent therapeutic approaches. PMID:25331179

  7. Assessment of quantitative and qualitative changes of proteoglycans and glycosaminoglycans in normal breast tissue during the follicular and luteal phases of the menstrual cycle.

    PubMed

    Júnior, J A Dos Santos; de Lima, C R; Michelacci, Y M C da Silva; Nazário, A C Pinto

    2015-01-01

    The effect of sex hormones on extracellular matrix compounds, such as proteoglycans (PGs) and glycosaminoglycans (GAGs), in mammary tissue remains poorly understood. The elucidation of extracellular matrix component functions could clarify pathophysiological conditions, such as cyclical mastalgia (breast pain). The authors examined the quantitative and qualitative changes of PGs and GAGs in normal breast tissue during the follicular and luteal phases of the menstrual cycle. Twenty-eight eumenorrheic patients with benign breast nodules were divided into groups: Group A included 15 follicular patients and Group B included 13 luteal phase patients. Breast tissue adjacent to the nodules was biochemically analyzed to evaluate the types and concentrations of PGS and GAGs. The distribution of proteoglycans during the menstrual cycle was analyzed with immunofluorescence. PG concentrations were elevated (p < 0.01) during the luteal phase compared with the follicular phase, whereas the concentrations of GAGs did not differ significantly. Immunofluorescence revealed that decorin was mainly found in the intralobular stroma. PG concentrations were elevated during the luteal phase, likely due to the influence of sex hormones on macromolecular synthesis. The PG decorin was observed in normal breast tissue in the intralobular stroma. Although the concentration of GAGs, including dermatan and heparan sulfate, varied cyclically, the differences were not significant.

  8. Formation of corpora lutea and central luteal cavities and their relationship with plasma progesterone levels and other metabolic parameters in dairy cattle.

    PubMed

    Perez-Marin, C

    2009-06-01

    The corpus luteum (CL) may be looked upon as a compact or cavitary structure. A number of papers have addressed the relationship between CL type and parameters such as fertility or progesterone levels. The present study assessed the morphological and functional sequence observed in cows with different CL types, comparing pre-ovulatory follicle size, progesterone levels, luteal tissue formation and some blood biochemical parameters (calcium, albumin, inorganic phosphorus, glucose, magnesium, copper and zinc), oestrus cycle length and oestrus expression, as a function of CL type. Twenty-eight lactating dairy cows from two commercial dairy farms in southern Spain were studied. Oestrus detection was performed by monitoring daily oestrus behaviour, and artificial insemination (AI) was performed using the AM/PM rule. Ovaries and uterus were sonographically examined and blood samples were collected to measure progesterone and various biochemical parameters. There was a slight tendency towards the appearance of luteal cavities when pre-ovulatory follicles were larger (1.9 +/- 0.2 vs 1.7 +/- 03; p = 0.074). Fertility was not affected by cavity presence (cavity = 42.9% and compact = 57.1%; n.s.). Luteal tissue and function were not modified as a function of CL type. Cows with luteal cavities displayed significantly higher levels of albumin, suggesting a possible metabolic influence on the formation of these structures, although specific research is required to confirm this observation.

  9. Effects of orexins A and B on expression of orexin receptors and progesterone release in luteal and granulosa ovarian cells.

    PubMed

    Cataldi, Natalia I; Lux-Lantos, Victoria A R; Libertun, Carlos

    2012-10-10

    Orexin-A and orexin-B are neuropeptides controlling sleep-wakefulness, feeding and neuroendocrine functions via their G protein-coupled receptors, orexin-1R and orexin-2R. They are synthesized in the lateral hypothalamus and project throughout the brain. Orexins and orexin receptors have also been described outside the brain. Previously we demonstrated the presence of both receptors in the ovary, their increased expression during proestrous afternoon and the dependence on the gonadotropins. Here we studied the effects of orexins on the mRNA expression of both receptors, by quantitative real-time PCR, on luteal cells from superovulated rat ovaries and granulosa cells from diethylstilbestrol-treated rat ovaries. Effects on progesterone secretion were also measured. In luteal cells, 1 nM of either orexin-A or orexin-B decreased progesterone secretion. Orexin-A treatment increased expression of both orexin-1R and orexin-2R mRNA. The effect on orexin-1R mRNA expression was abolished by an orexin-1R selective receptor antagonist SB-334867 and the effect on orexin-2R mRNA expression was abolished by a selective orexin-2R antagonist JNJ-10397049. Orexin-B did not modify orexin-1R mRNA expression, but increased orexin-2R mRNA expression. The effect of orexin-B on orexin-2R was abolished by a selective orexin-2R antagonist. Neither the expression of orexin receptors nor progesterone secretions by granulosa cells were affected by orexins. FSH, as positive control, increased both steroid hormones secretion, but did not induce the expression of OX receptors in granulosa cells isolated from late preantral/early antral follicles. Finally in ovaries obtained immediately after sacrifice, the expression of orexin-1R and orexin-2R was higher in superovulated rat ovaries compared to control or diethylstilbestrol treated rat ovaries. A selective presence and function of both orexinergic receptors in luteal and granulosa cells is described, suggesting that the orexinergic system may

  10. Molecular Signatures of Immune Activation and Epithelial Barrier Remodeling Are Enhanced during the Luteal Phase of the Menstrual Cycle: Implications for HIV Susceptibility

    PubMed Central

    Arnold, Kelly B.; Novak, Richard M.; McCorrister, Stuart; Shaw, Souradet; Westmacott, Garrett R.; Ball, Terry B.; Lauffenburger, Douglas A.; Burgener, Adam

    2015-01-01

    ABSTRACT The variable infectivity and transmissibility of HIV/SHIV has been recently associated with the menstrual cycle, with particular susceptibility observed during the luteal phase in nonhuman primate models and ex vivo human explant cultures, but the mechanism is poorly understood. Here, we performed an unbiased, mass spectrometry-based proteomic analysis to better understand the mucosal immunological processes underpinning this observed susceptibility to HIV infection. Cervicovaginal lavage samples (n = 19) were collected, characterized as follicular or luteal phase using days since last menstrual period, and analyzed by tandem mass spectrometry. Biological insights from these data were gained using a spectrum of computational methods, including hierarchical clustering, pathway analysis, gene set enrichment analysis, and partial least-squares discriminant analysis with LASSO feature selection. Of the 384 proteins identified, 43 were differentially abundant between phases (P < 0.05, ≥2-fold change). Cell-cell adhesion proteins and antiproteases were reduced, and leukocyte recruitment (interleukin-8 pathway, P = 1.41E–5) and extravasation proteins (P = 5.62E–4) were elevated during the luteal phase. LASSO/PLSDA identified a minimal profile of 18 proteins that best distinguished the luteal phase. This profile included cytoskeletal elements and proteases known to be involved in cellular movement. Gene set enrichment analysis associated CD4+ T cell and neutrophil gene set signatures with the luteal phase (P < 0.05). Taken together, our findings indicate a strong association between proteins involved in tissue remodeling and leukocyte infiltration with the luteal phase, which may represent potential hormone-associated mechanisms of increased susceptibility to HIV. IMPORTANCE Recent studies have discovered an enhanced susceptibility to HIV infection during the progesterone-dominant luteal phase of the menstrual cycle. However, the mechanism responsible for

  11. Ridge Regression Signal Processing

    NASA Technical Reports Server (NTRS)

    Kuhl, Mark R.

    1990-01-01

    The introduction of the Global Positioning System (GPS) into the National Airspace System (NAS) necessitates the development of Receiver Autonomous Integrity Monitoring (RAIM) techniques. In order to guarantee a certain level of integrity, a thorough understanding of modern estimation techniques applied to navigational problems is required. The extended Kalman filter (EKF) is derived and analyzed under poor geometry conditions. It was found that the performance of the EKF is difficult to predict, since the EKF is designed for a Gaussian environment. A novel approach is implemented which incorporates ridge regression to explain the behavior of an EKF in the presence of dynamics under poor geometry conditions. The basic principles of ridge regression theory are presented, followed by the derivation of a linearized recursive ridge estimator. Computer simulations are performed to confirm the underlying theory and to provide a comparative analysis of the EKF and the recursive ridge estimator.

  12. Husbandry factors and the resumption of luteal activity in open and zero-grazed dairy cows in urban and peri-urban kampala, Uganda.

    PubMed

    Kanyima, B M; Båge, R; Owiny, D O; Ntallaris, T; Lindahl, J; Magnusson, U; Nassuna-Musoke, M G

    2014-08-01

    The study investigated the influence of selected husbandry factors on interval to resumption of post-partum cyclicity among dairy cows in urban and peri-urban Kampala. A prospective study of 85 day post-partum period of 59 dairy cows in open (n = 38) and zero grazing (n = 21) systems was conducted on 24 farms. Cows of parity 1-6 were recruited starting 15-30 days post-partum. Progesterone (P4) content in milk taken at 10-12 day intervals was analysed using ELISA. The cow P4 profiles were classified into 'normal' (< 56 days), 'delayed' (> 56 days), 'ceased' or 'prolonged' (if started < 56 days but with abnormal P4 displays) resumption of luteal activity and tested for association with husbandry and cow factors. Of the 59 cows, luteal activity in 81.4% resumed normally and in 18.6%, delayed. Only 23.7% maintained regular luteal activity, while the others had ceased (10.2%), prolonged (37.3%) or unclear luteal activity (20.3%). There were no differences between open and zero-grazed cows. Milk production was higher (p < 0.05) in zero than open grazing, in urban than peri-urban and in cows fed on brew waste (p < 0.001) compared with mill products and banana peels. Results suggest that luteal activity resumes normally in a majority of cows, although only a minority experienced continued normal cyclicity once ovulation had occurred, in the two farming systems irrespective of feed supplements or water, and that supplementing with brew waste is beneficial for milk production. PMID:24930481

  13. Prolactin involvement in the regulation of the hypothalamic-pituitary-ovarian axis during the early luteal phase of the porcine estrous cycle.

    PubMed

    Ciereszko, R; Opałka, M; Kamińska, B; Kamiński, T; Dusza, L

    2002-01-23

    Our previous in vivo and in vitro studies revealed that prolactin (PRL) affected luteal function during the first days of the porcine estrous cycle. Since the mechanism by which the luteotrophic action of PRL might be mediated was not elucidated, the goal of the present study is to investigate the effects of short term, in vivo administration of PRL on in vitro functions of hypothalamic explants, adenohypophyseal cells and luteal cells of sows. Injections of PRL or saline (performed every 2h) started shortly after the preovulatory LH surge and lasted for 2 or 3 days. Peripheral blood plasma for determination of LH, PRL and progesterone (P(4)) was sampled at 4h intervals. Ovaries, pituitaries and the stalk median eminence (SME) dissected after slaughter were used for in vitro studies. Luteal and adenohypophysial cells as well as hypothalamic tissue were incubated/cultured with different treatments. Medium and plasma levels of GnRH, LH and P(4) were quantified by radioimmunoassays (RIAs). Corpora lutea (CL) were used for LH/human chorionic gonadotrophin (hCG) receptor analysis. In vivo and in vitro treatment with PRL increased the in vitro GnRH release by hypothalamic explants (P<0.05). GnRH-stimulated LH production was enhanced in PRL-treated sows compared to that of control sows (P<0.05). PRL injections had no effect on plasma P(4) concentrations during the treatment period. However, luteal secretion of P(4) (P=0.06) and LH/hCG receptor concentration (P=0.079) tended to be higher in PRL-treated sows in comparison to those of controls. The results indicate that PRL may be involved in the regulation of the hypothalamic-pituitary-ovarian axis at the beginning of the luteal phase of the porcine estrous cycle.

  14. Husbandry Factors and the Resumption of Luteal Activity in Open and Zero-Grazed Dairy Cows in Urban and Peri-Urban Kampala, Uganda

    PubMed Central

    Kanyima, BM; Båge, R; Owiny, DO; Ntallaris, T; Lindahl, J; Magnusson, U; Nassuna-Musoke, MG

    2014-01-01

    Contents The study investigated the influence of selected husbandry factors on interval to resumption of post-partum cyclicity among dairy cows in urban and peri-urban Kampala. A prospective study of 85 day post-partum period of 59 dairy cows in open (n = 38) and zero grazing (n = 21) systems was conducted on 24 farms. Cows of parity 1–6 were recruited starting 15–30 days post-partum. Progesterone (P4) content in milk taken at 10–12 day intervals was analysed using ELISA. The cow P4 profiles were classified into ‘normal’ (< 56 days), ‘delayed’ (> 56 days), ‘ceased’ or ‘prolonged’ (if started < 56 days but with abnormal P4 displays) resumption of luteal activity and tested for association with husbandry and cow factors. Of the 59 cows, luteal activity in 81.4% resumed normally and in 18.6%, delayed. Only 23.7% maintained regular luteal activity, while the others had ceased (10.2%), prolonged (37.3%) or unclear luteal activity (20.3%). There were no differences between open and zero-grazed cows. Milk production was higher (p < 0.05) in zero than open grazing, in urban than peri-urban and in cows fed on brew waste (p < 0.001) compared with mill products and banana peels. Results suggest that luteal activity resumes normally in a majority of cows, although only a minority experienced continued normal cyclicity once ovulation had occurred, in the two farming systems irrespective of feed supplements or water, and that supplementing with brew waste is beneficial for milk production. PMID:24930481

  15. Effect of HIF-1a/VEGF signaling pathway on plasma progesterone and ovarian prostaglandin F₂a secretion during luteal development of pseudopregnant rats.

    PubMed

    Pan, X Y; Zhang, Z H; Wu, L X; Wang, Z C

    2015-08-03

    The corpus luteum is a temporary endocrine structure in mammals that plays an important role in the female reproductive cycle and is formed from a ruptured and ovulated follicle with rapid angiogenesis. Vascular endothelial growth factor (VEGF) is thought to be vital in normal and abnormal angiogenesis in the ovary, but the molecular regulation of luteal VEGF expression during corpus luteum development in vivo is still poorly understood at present. Therefore, we examined whether hypoxia-inducible factor-1a (HIF-1a) is induced and regulates VEGF expression and luteal function in vivo using a pseudopregnant rat model treated with a small-molecule inhibitor of HIF-1a, echinomycin. Corpus luteum development in the pseudopregnant rat ovary was determined after measuring plasma progesterone concentration and ovarian prostaglandin F2a content to reflect changes in HIF-1a and VEGF on different days of this developmental process. At day 7, the corpus luteum was formed and the expression of HIF- 1a/VEGF reached a maximum, while a significant decrease in HIF-1a/ VEGF expression was observed when luteolysis occurred at day 13. Additionally, echinomycin blocked luteal development by inhibiting VEGF expression mediated by HIF-1a and following luteal function by detecting the progesterone changes at day 7. These results demonstrated that HIF-1a-mediated VEGF expression might be an important mechanism regulating ovarian luteal development in mammals in vivo, which may provide new strategies for fertility control and for treating some types of ovarian dysfunction, such as polycystic ovarian syndrome, ovarian hyperstimulation syndrome, and ovarian neoplasia.

  16. Tumor necrosis factor (TNF)-alpha-induced IL-8 expression in gastric epithelial cells: role of reactive oxygen species and AP endonuclease-1/redox factor (Ref)-1.

    PubMed

    O'Hara, Ann M; Bhattacharyya, Asima; Bai, Jie; Mifflin, Randy C; Ernst, Peter B; Mitra, Sankar; Crowe, Sheila E

    2009-06-01

    TNF-alpha contributes to oxidative stress via induction of reactive oxygen species (ROS) and pro-inflammatory cytokines. The molecular basis of this is not well understood but it is partly mediated through the inducible expression of IL-8. As redox factor-1 (Ref-1), is an important mediator of redox-regulated gene expression we investigated whether ROS and Ref-1 modulate TNF-alpha-induced IL-8 expression in human gastric epithelial cells. We found that TNF-alpha treatment of AGS cells enhanced nuclear expression of Ref-1 and potently induced IL-8 expression. Overexpression of Ref-1 enhanced IL-8 gene transcription at baseline and after TNF-alpha treatment whereas Ref-1 suppression and antioxidant treatment inhibited TNF-alpha-stimulated IL-8 expression. TNF-alpha-mediated enhancement of other pro-inflammatory chemokines like MIP-3 alpha and Gro-alpha was also regulated by Ref-1. Although TNF-alpha increased DNA binding activity of Ref-1-regulated transcription factors, AP-1 and NF-kappaB, to the IL-8 promoter, promoter activity was mainly mediated by NF-kappaB binding. Silencing of Ref-1 in AGS cells inhibited basal and TNF-alpha-induced AP-1 and NF-kappaB DNA binding activity, but not their nuclear accumulation. Collectively, we provide the first mechanistic evidence of Ref-1 involvement in TNF-alpha-mediated, redox-sensitive induction of IL-8 and other chemokines in human gastric mucosa. This has implications for understanding the pathogenesis of gastrointestinal inflammatory disorders.

  17. Eicosapentaenoic acid and docosahexaenoic acid reduce UVB- and TNF-alpha-induced IL-8 secretion in keratinocytes and UVB-induced IL-8 in fibroblasts.

    PubMed

    Storey, Amy; McArdle, Frank; Friedmann, Peter S; Jackson, Malcolm J; Rhodes, Lesley E

    2005-01-01

    Omega-3 polyunsaturated fatty acids (n-3 PUFA) inhibit ultraviolet B (UVB)-induced inflammation and other inflammatory states, in vivo. We examined whether this may be mediated by modulation of interleukin (IL)-8, a chemokine pivotal to skin inflammation induced by UVB, in epidermal and dermal cells. We also explored the ability of n-3 PUFA to protect against tumor necrosis factor (TNF)-alpha induction of IL-8, and assessed relative potencies of the principal dietary n-3 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Pre-supplementation, both HaCaT keratinocyte and CCD922SK fibroblast cell lines showed dose-responses for UVB-induced IL-8 release (p<0.001), assessed 48 h post-irradiation. Cells were supplemented with > or =90% purified EPA, DHA, oleic acid (OA) or vehicle control, for 4.5 d. EPA and DHA supplements were bioavailable to keratinocytes and fibroblasts. In keratinocytes, EPA and DHA were shown to reduce basal secretion of IL-8 by 66% and 63%, respectively (p<0.05), and UVB-induced levels by 66% and 65% at 48 h after 100 mJ per cm2, respectively, (p<0.01). A similar pattern occurred in fibroblasts, whereas OA had no influence on IL-8 release in either cell line. In addition, TNF-alpha-induced IL-8 secretion by keratinocytes was reduced by 54% and 42%, respectively, by EPA and DHA (p<0.001). Hence both n-3 PUFA inhibit production of UVB- and TNF-alpha-induced IL-8 in skin cells; this may be important in the photoprotective and other anti-inflammatory effects conferred by these agents.

  18. Status of autophagy, lysosome activity and apoptosis during corpus luteum regression in cattle

    PubMed Central

    ABOELENAIN, Mansour; KAWAHARA, Manabu; BALBOULA, Ahmed Zaky; MONTASSER, Abd El-monem; ZAABEL, Samy Mowaed; OKUDA, Kiyoshi; TAKAHASHI, Masashi

    2015-01-01

    Corpus luteum (CL) regression is required during the estrous cycle. During CL regression, luteal cells stop producing progesterone and are degraded by apoptosis. However, the detailed mechanism of CL regression in cattle has not been fully elucidated. The aim of this study was to evaluate autophagy, lysosome activity, and apoptosis during CL regression in cattle. The expression of autophagy-related genes (LC3α, LC3β, Atg3, and Atg7) and the protein LC3-II was significantly higher in the late CL than in the mid CL. In addition, autophagy activity was significantly increased in the late CL. Moreover, gene expression of the autophagy inhibitor mammalian target of rapamycin (mTOR) was significantly lower in the late CL than in the mid CL. Lysosome activation and expression of cathepsin-related genes (CTSB, CTSD, and CTSZ) showed significant increases in the late CL and were associated with an increase in cathepsin B protein. In addition, mRNA expression and activity of caspase 3 (CASP3), an apoptotic enzyme, were significantly higher in the late CL than in the mid CL. These results suggest simultaneous upregulation of autophagy-related factors, lysosomal enzymes and apoptotic mediators, which are involved in regression of the bovine CL. PMID:25819401

  19. Crinone Gel for Luteal Phase Support in Frozen-Thawed Embryo Transfer Cycles: A Prospective Randomized Clinical Trial in the Chinese Population

    PubMed Central

    Zhao, Xiaoming; Ji, Xiaowei; Hong, Yan; Wang, Yuan; Zhu, Qinling; Xu, Bin; Sun, Yun

    2015-01-01

    To compare Crinone vaginal progesterone gel with intramuscularly injected progesterone for luteal phase support in progesterone-supplemented frozen-thawed embryo transfer (FET) cycles, a randomized prospective study of patients qualified for FET was conducted between September 2010 and January 2013 at a hospital in Shanghai, China. From the day of transformation into secretory phase endometrium (day 0), Crinone vaginal gel (90 mg/d) was administered to patients in the Gel Group, while progesterone (40 mg/d) was injected intramuscularly in patients in the Inj Group (n = 750 per group). All patients received oral dydrogesterone (20 mg/d) and estradiol valerate (4–8 mg/d). Day 3 embryos with the highest pre-frozen scores were transferred to patients in the two groups and the clinical outcomes compared. This study comprised 1,500 cycles (750 in each group). Twenty-nine cycles in the Gel Group and 24 in the Inj Group were withdrawn. There were no significant differences between groups in age, endometrial thickness, endometrial preparation time or number of embryos transferred. No significant differences were observed between the Gel Group and Inj Group in the rates of live birth (32.6% vs. 31.7%, P = 0.71), clinical pregnancy (40.1% vs. 40.6%, P = 0.831), implantation (25.8% vs. 25.3%, P = 0.772), abortion (16.3% vs. 18.3%, P = 0.514) or ectopic pregnancy (2.8% vs. 4.4%, P = 0.288). Multivariate logistic regression analysis revealed that the odds ratios (95% confidence intervals) for the rates of live birth, clinical pregnancy, abortion and ectopic pregnancy (Gel Group relative to Inj Group) were 1.036 (0.829–1.295), 0.971 (0.785–1.200), 0.919 (0.595–1.420) and 0.649 (0.261–1.614), respectively. Our study revealed that using Crinone vaginal gel in FET cycles achieved similar pregnancy outcomes to intramuscular progesterone, indicating that vaginal gel is a viable alternative to intramuscular injection. Trial Registration Chinese Clinical Trial Registry Chi

  20. eCG concentrations, luteal structures, return to cyclicity, and postabortion fertility in embryo transfer recipient mares.

    PubMed

    Cuervo-Arango, J; Aguilar, J J; Vettorazzi, M L; Martínez-Boví, R

    2015-10-01

    The present study characterizes the relationship between the levels of eCG, ovarian morphology, resumption of cyclicity, and fertility in postaborted embryo transfer recipient mares. A total of 32 pregnant recipient mares carrying a male fetus were aborted at approximately 65 days of gestation by single transcervical administration of cloprostenol. In addition, 25 gestation age-matched mares were used as nonaborted controls. The concentration of progesterone, but not of eCG, differed significantly between controls and aborted mares 48 hours after abortion. Of treated mares, 84.4% (27 of 32) expelled the fetus within 48 hours of treatment. The eCG concentration and the number of supplementary luteal structures were lower in mares aborted in November (equivalent to May in Northern Hemisphere) than in January. A total of 6.2%, 37.5%, and 56.2% of the mares entered anestrus, ovulated normally, and had 1 to 2 consecutive anovulatory cycles, respectively. The mean interval from abortion to the first ovulation was 28.5 ± 3.3 days (range, 5-65 days). The correlation between the levels of eCG at abortion and the interval to the first ovulation was poor (r = 0.38; P = 0.03). Of aborted mares, 90% (18 of 20) were reused and became pregnant after embryo transfer at a mean of 57.6 ± 4.4 days after abortion (range, 19-103 days) and eCG concentration of 0.9 ± 0.3 IU/mL (range, 0.1-3.6 IU/mL). In conclusion, the levels of eCG at the time of abortion were extremely variable and did not correlate well with the number of luteal structures or the interval from abortion to the first ovulation.

  1. Orthogonal Regression: A Teaching Perspective

    ERIC Educational Resources Information Center

    Carr, James R.

    2012-01-01

    A well-known approach to linear least squares regression is that which involves minimizing the sum of squared orthogonal projections of data points onto the best fit line. This form of regression is known as orthogonal regression, and the linear model that it yields is known as the major axis. A similar method, reduced major axis regression, is…

  2. Structural regression trees

    SciTech Connect

    Kramer, S.

    1996-12-31

    In many real-world domains the task of machine learning algorithms is to learn a theory for predicting numerical values. In particular several standard test domains used in Inductive Logic Programming (ILP) are concerned with predicting numerical values from examples and relational and mostly non-determinate background knowledge. However, so far no ILP algorithm except one can predict numbers and cope with nondeterminate background knowledge. (The only exception is a covering algorithm called FORS.) In this paper we present Structural Regression Trees (SRT), a new algorithm which can be applied to the above class of problems. SRT integrates the statistical method of regression trees into ILP. It constructs a tree containing a literal (an atomic formula or its negation) or a conjunction of literals in each node, and assigns a numerical value to each leaf. SRT provides more comprehensible results than purely statistical methods, and can be applied to a class of problems most other ILP systems cannot handle. Experiments in several real-world domains demonstrate that the approach is competitive with existing methods, indicating that the advantages are not at the expense of predictive accuracy.

  3. CSWS-related autistic regression versus autistic regression without CSWS.

    PubMed

    Tuchman, Roberto

    2009-08-01

    Continuous spike-waves during slow-wave sleep (CSWS) and Landau-Kleffner syndrome (LKS) are two clinical epileptic syndromes that are associated with the electroencephalography (EEG) pattern of electrical status epilepticus during slow wave sleep (ESES). Autistic regression occurs in approximately 30% of children with autism and is associated with an epileptiform EEG in approximately 20%. The behavioral phenotypes of CSWS, LKS, and autistic regression overlap. However, the differences in age of regression, degree and type of regression, and frequency of epilepsy and EEG abnormalities suggest that these are distinct phenotypes. CSWS with autistic regression is rare, as is autistic regression associated with ESES. The pathophysiology and as such the treatment implications for children with CSWS and autistic regression are distinct from those with autistic regression without CSWS.

  4. Tumour necrosis factor-alpha-induced ICAM-1 expression in human vascular endothelial and lung epithelial cells: modulation by tyrosine kinase inhibitors.

    PubMed Central

    Burke-Gaffney, A.; Hellewell, P. G.

    1996-01-01

    1. Tumour necrosis factor-alpha (TNF alpha) increases the expression of the adhesion molecule intercellular adhesion molecule-1 (ICAM-1) on cultured endothelial and epithelial cells and modulation of this may be important in controlling inflammation. Activation of tyrosine kinase(s) is known to be involved in the signal transduction pathways of many cytokines. In this study we have investigated the effects of the tyrosine kinase inhibitors, ST638, tyrphostin AG 1288 and genistein, on TNF alpha-induced ICAM-1 expression in human alveolar epithelial (A549) and vascular endothelial (EAhy926) cell lines and also normal human lung microvascular endothelial cells (HLMVEC). 2. ICAM-1 expression on cultured cells was determined by a sensitive enzyme-linked immunosorbant assay (ELISA). Endothelial or epithelial monolayers were exposed to increasing doses of TNF-alpha (0.01-10 ng ml-1), in the presence or absence of either ST638 (3-100 microM), AG 1288 (3-100 microM) or genistein (100 microM) and ICAM-1 expression was measured at 4 and 24 h. Control experiments examined the effect of ST638 on phorbol 12-myristate 13-acetate (PMA, 20 ng ml-1, 4 h)-stimulated ICAM-1 and compared it to that of a specific protein kinase C inhibitor, R031-8220 (10 microM). Also, functional consequences of changes in ICAM-1 expression were assessed by measuring adhesion of 111 In-labelled human neutrophils to EAhy926 endothelial and A549 epithelial monolayers treated with TNF alpha, in the presence or absence of ST638. 3. ST638 caused a concentration-dependent reduction in TNF alpha- (0.1-10 ng ml-1)-induced ICAM-1 on EAhy926 endothelial (at 4 h) and A549 epithelial monolayers (at 4 and 24 h). In contrast, ST638 caused a concentration-dependent increase in TNF alpha- (0.1-10 ng ml-1)-induced ICAM-1 on EAhy926 endothelial cells at 24 h. Similar effects were seen with AG 1288 or genistein. ST638 (100 microM) significantly (P < 0.01) inhibited ICAM-1 expression on HLMVEC endothelial cells induced by

  5. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

    SciTech Connect

    Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there

  6. Experimental study on inhibitory effect of niacinamide on tumor necrosis factor-alpha-induced matrix degradation of annulus fibrous tissue in vitro.

    PubMed

    Xu, Runbing; Shao, Zengwu; Xiong, Liming

    2008-10-01

    The inhibitory effect of niacinamide on tumor necrosis factor-alpha (TNF-alpha) induced annulus fibrous (AF) degradation was assessed, and the mechanism of the inhibition was investigated. Chiba's intervertebral disc (IVD) culture model was established. Forty-eight IVDs from 12 adult Japanese white rabbits were randomly divided into 4 groups (12 IVDs in each group), and various concentrations of niacinamide and TNF-alpha were added to the medium for intervention: negative control group, niacinamide control group (0.5 mg/mL niacinamide), degeneration group (10 ng/mL TNF-alpha), and treatment group (0.5 mg/mL niacinamide and 10 ng/mL TNF-alpha). After one week's culture, AFs were collected for glycosaminoglycan (GS) content measurement, safranin O-fast green staining, and immunohistochemical staining for type I, II collagen and cysteine containing aspartate specific protease-3 (Caspase-3). It was found that the GS content in treatment group was increased by about 48% as compared with degeneration group (t=16.93, P<0.001), and close to that in niacinamide control group (t=0.71, P=0.667). Safranine O-fast green staining exhibited higher staining density and better histological structure of AF in the treatment group as compared with the degeneration group. Immunohistochemical staining for both Type I and II collagen demonstrated that lamellar structure and continuity of collagen in treatment group were better reserved than in degeneration group. Positive staining rate of Caspase-3 in AFs of negative control group, niacinamide control group, degeneration group and treatment group was 3.4%, 4.3%, 17.9% and 10.3% respectively. The positive rate in treatment group was significantly lower than in degeneration group (P<0.01). It was concluded that niacinamide could effectively alleviate TNF-alpha induced destruction and synthesis inhibition of matrix ingredients in AFs. The inhibition may be related with reduction of expression of Caspase-3. Thus, niacinamide is of potential

  7. Genistein reduces tumor necrosis factor alpha-induced plasminogen activator inhibitor-1 transcription but not urokinase expression in human endothelial cells.

    PubMed

    van Hinsbergh, V W; Vermeer, M; Koolwijk, P; Grimbergen, J; Kooistra, T

    1994-11-01

    The plasminogen activator inhibitor PAI-1 is markedly elevated in vivo and in vitro upon exposure to the inflammatory mediators tumor necrosis factor alpha (TNF alpha), interleukin-1 (IL-1), and bacterial lipopolysaccharide. Here we report that the isoflavone compound genistein prevents the increase in synthesis of PAI-1 induced by these inflammatory mediators in human endothelial cells in vitro, and partially reduces the basal PAI-1 production by these cells. These effects of genistein were accompanied by a decrease in PAI-1 mRNA and in a suppression of the PAI-1 transcription rate as shown by run-on assay. A specific action of genistein, probably by inhibiting a tyrosine protein kinase, is likely, because the structural genistein analogue daidzein, which has a low tyrosine protein kinase inhibitor activity, did not inhibit PAI-1 synthesis. Vanadate, a tyrosine protein phosphatase inhibitor, increased PAI-1 production. The effect of genistein on PAI-1 synthesis was rather selective. Herbimycin A also reduced PAI-1 synthesis, but several other tyrosine protein kinase inhibitors, namely tyrphostin A47, methyl-2,5-dihydroxy-cinnamate, and compound 5, were unable to do so. All these tyrosine protein kinase inhibitors reduced basic fibroblast growth factor (b-FGF)-induced [3H]thymidine incorporation in endothelial cells. This indicates that the effect of genistein on PAI-1 transcription proceeds independently of its effect on mitogenesis. In contrast to TNF-alpha-induced PAI-1 production, the transcription and synthesis of urokinase-type plasminogen activator (u-PA) was not inhibited by genistein. A TNF-alpha-mutant (Trp32Thr86TNF alpha) that specifically recognizes the 55-kD TNF-receptor, mimicked the effects of TNF alpha on both PAI-1 and u-PA. Because genistein affected PAI-1, but not u-PA induced by this mutant, involvement of different TNF-receptors cannot underlie the difference in the effects of genistein on PAI-1 and u-PA synthesis. Because genistein also

  8. Overexpression of cellular repressor of E1A-stimulated genes inhibits TNF-{alpha}-induced apoptosis via NF-{kappa}B in mesenchymal stem cells

    SciTech Connect

    Peng, Cheng-Fei; Han, Ya-Ling; Jie-Deng,; Yan, Cheng-Hui; Jian-Kang,; Bo-Luan,; Jie-Li

    2011-03-25

    Research highlights: {yields} CREG protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis. {yields} CREG inhibits the phosphorylation of I{kappa}B{alpha} and prevents the activation of NF-{kappa}B. {yields} CREG inhibits NF-{kappa}B nuclear translocation and pro-apoptosis protein transcription. {yields} CREG anti-apoptotic effect involves inhibition of the death receptor pathway. {yields} p53 is downregulated by CREG via NF-{kappa}B pathway under TNF-{alpha} stimulation. -- Abstract: Bone marrow-derived mesenchymal stem cells (MSCs) show great potential for therapeutic repair after myocardial infarction. However, poor viability of transplanted MSCs in the ischemic heart has limited their use. Cellular repressor of E1A-stimulated genes (CREG) has been identified as a potent inhibitor of apoptosis. This study therefore aimed to determine if rat bone marrow MSCs transfected with CREG-were able to effectively resist apoptosis induced by inflammatory mediators, and to demonstrate the mechanism of CREG action. Apoptosis was determined by flow cytometric and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling assays. The pathways mediating these apoptotic effects were investigated by Western blotting. Overexpression of CREG markedly protected MSCs from tumor necrosis factor-{alpha} (TNF-{alpha}) induced apoptosis by 50% after 10 h, through inhibition of the death-receptor-mediated apoptotic pathway, leading to attenuation of caspase-8 and caspase-3. Moreover, CREG resisted the serine phosphorylation of I{kappa}B{alpha} and prevented the nuclear translocation of the transcription factor nuclear factor-{kappa}B (NF-{kappa}B) under TNF-{alpha} stimulation. Treatment of cells with the NF-{kappa}B inhibitor pyrrolidine dithiocarbamate (PDTC) significantly increased the transcription of pro-apoptosis proteins (p53 and Fas) by NF-{kappa}B, and attenuated the anti-apoptotic effects of CREG on MSCs. The results of this study

  9. Insulin-like growth factor-binding protein-5 (IGFBP-5) inhibits TNF-{alpha}-induced NF-{kappa}B activity by binding to TNFR1

    SciTech Connect

    Hwang, Jae Ryoung; Huh, Jae Ho; Lee, Yoonna; Lee, Sang Il; Rho, Seung Bae; Lee, Je-Ho

    2011-02-25

    Research highlights: {yields} Binding assays demonstrated that secreted- and cellular-IGFBP-5 interacted with TNFR1. {yields} The interaction between IGFBP-5 and TNFR1 was inhibited by TNF-{alpha} and was blocked TNF-{alpha}-activated NF-{kappa}B activity. {yields} IGFBP-5 interacted with TNFR1 through its N- and L-domains but the binding of L-domain to TNFR1 was blocked by TNF-{alpha}. {yields} Competition between the L-domain of IGFBP-5 and TNF-{alpha} blocked TNF-{alpha}-induced NF-{kappa}B activity. {yields} This study suggests that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF-{alpha} inhibitor. -- Abstract: IGFBP-5 is known to be involved in various cell phenomena such as proliferation, differentiation, and apoptosis. However, the exact mechanisms by which IGFBP-5 exerts its functions are unclear. In this study, we demonstrate for the first time that IGFBP-5 is a TNFR1-interacting protein. We found that ectopic expression of IGFBP-5 induced TNFR1 gene expression, and that IGFBP-5 interacted with TNFR1 in both an in vivo and an in vitro system. Secreted IGFBP-5 interacted with GST-TNFR1 and this interaction was blocked by TNF-{alpha}, demonstrating that IGFBP-5 might be a TNFR1 ligand. Furthermore, conditioned media containing secreted IGFBP-5 inhibited PMA-induced NF-{kappa}B activity and IL-6 expression in U-937 cells. Coimmunoprecipitation assays of TNFR1 and IGFBP-5 wild-type and truncation mutants revealed that IGFBP-5 interacts with TNFR1 through its N- and L-domains. However, only the interaction between the L-domain of IGFBP-5 and TNFR1 was blocked by TNF-{alpha} in a dose-dependent manner, suggesting that the L-domain of IGFBP-5 can function as a TNFR1 ligand. Competition between the L-domain of IGFBP-5 and TNF-{alpha} resulted in inhibition of TNF-{alpha}-induced NF-{kappa}{Beta} activity. Taken together, our results suggest that the L-domain of IGFBP-5 is a novel TNFR1 ligand that functions as a competitive TNF

  10. The Effects of Smoked Nicotine on Measures of Subjective states and Hypothalamic-Pituitary-Adrenal Axis Hormones in Women during the Follicular and Luteal Phases of the Menstrual Cycle

    PubMed Central

    Goletiani, Nathalie V.; Siegel, Arthur J.; Lukas, Scott E.; Hudson, James I.

    2015-01-01

    Objectives To determine the acute effects of cigarette smoking on hypothalamic-pituitary-adrenal axis (HPA) hormones and subjective states as a function of the menstrual cycle in nicotine-dependent women. Methods Seventeen healthy nicotine-dependent women were studied during the follicular and/or luteal phase of the menstrual cycle. Due to observation of a possible bimodal distribution of progesterone levels within the luteal phase group, we performed a set of a posteriori analyses. Therefore, we divided the luteal group into a low progesterone and a high progesterone groups. Results Smoked nicotine activated HPA, measured by ACTH, cortisol, and DHEA response and affected subjective states in both follicular and luteal phases, with increased “High”, “Rush”, and decreased “Craving”. The HPA stimulation revealed a blunting of ACTH response. There was only modest evidence for a blunting of subjective state responses in the luteal phase. However upon post hoc analyses, the high progesterone luteal group showed a marked blunting of measures of subjective states and a blunted ACTH response. Examining the association between hormone and measures of subjective states revealed tentative associations of ACTH stimulation with increased “Rush” and “Craving”, and DHEA stimulation with increased “Craving”. Conclusions This pilot study suggests that menstrual cycle phase differences in progesterone levels may attenuate nicotine’s addictive effects via diminution of its reinforcing properties, and augmentation of its aversive effects interfering with the pleasure associated with cigarette smoking. PMID:25783522

  11. Contribution to More Patient-Friendly ART Treatment: Efficacy of Continuous Low-Dose GnRH Agonist as the Only Luteal Support—Results of a Prospective, Randomized, Comparative Study

    PubMed Central

    Pirard, Céline; Loumaye, Ernest; Wyns, Christine

    2015-01-01

    Background. The aim of this pilot study was to evaluate intranasal buserelin for luteal phase support and compare its efficacy with standard vaginal progesterone in IVF/ICSI antagonist cycles. Methods. This is a prospective, randomized, open, parallel group study. Forty patients underwent ovarian hyperstimulation with human menopausal gonadotropin under pituitary inhibition with gonadotropin-releasing hormone antagonist, while ovulation trigger and luteal support were achieved using intranasal GnRH agonist (group A). Twenty patients had their cycle downregulated with buserelin and stimulated with hMG, while ovulation trigger was achieved using 10,000 IU human chorionic gonadotropin with luteal support by intravaginal progesterone (group B). Results. No difference was observed in estradiol levels. Progesterone levels on day 5 were significantly lower in group A. However, significantly higher levels of luteinizing hormone were observed in group A during the entire luteal phase. Pregnancy rates (31.4% versus 22.2%), implantation rates (22% versus 15.4%), and clinical pregnancy rates (25.7% versus 16.7%) were not statistically different between groups, although a trend towards higher rates was observed in group A. No luteal phase lasting less than 10 days was recorded in either group. Conclusion. Intranasal administration of buserelin is effective for providing luteal phase support in IVF/ICSI antagonist protocols. PMID:25945092

  12. Impact of buserelin acetate or hCG administration on day 12 post-ovulation on subsequent luteal profile and conception rate in buffalo (Bubalus bubalis).

    PubMed

    Pandey, A K; Ghuman, S P S; Dhaliwal, G S; Kumar, Ajeet; Agarwal, S K

    2013-01-30

    The present study investigated the impact of gonadotropic hormone administration on day 12 post-ovulation on subsequent luteal profile and conception rate in buffaloes. All the buffaloes (n=48) were estrus synchronized by a synthetic analogue of prostaglandin F(2α) (PGF(2α)), administered 11 days apart, followed by insemination during mid to late estrus. To examine the effect of mid-luteal phase hormonal treatment, buffaloes were randomly divided into control (normal saline, n=14), d12-BA (buserelin acetate, 20μg, n=17) and d12-hCG (hCG, 3000IU, n=17) groups. Ovaries were scanned on the day of induced estrus to measure the preovulatory follicle (POF) diameter and on days 5, 12, 16 and 21 post-ovulation to examine the alterations in corpus luteum (CL) diameter. On the day of each sonography, blood samples were collected for the estimation of plasma progesterone. In treatment groups, luteal profile (CL diameter and plasma progesterone) on day 16-21 post-ovulation was better (P<0.05) as well as first service conception rate was higher (52.9% in each treatment group vs. 28.6%, P>0.05) compared to controls. All the pregnant buffaloes exhibited higher (P<0.05) plasma progesterone on various post-ovulation days than their respective non-pregnant counterparts. Treatment-induced accessory corpus luteum (ACL) formation was observed in 58.8 per cent and 70.6 per cent buffaloes of d12-BA and d12-hCG group, respectively, that also had higher (P<0.05) plasma progesterone compared to controls. Compared to the spontaneous CL, the diameter of ACL was less (P<0.05) in the treatment groups. In conclusion, buserelin acetate and hCG administration on day 12 post-ovulation leads to accessory CL formation, improves luteal profile and consequently increases conception rate in buffaloes.

  13. Infertility in a line of mice with the high growth mutation is due to luteal insufficiency resulting from disruption at the hypothalamic-pituitary axis.

    PubMed

    Cargill, S L; Medrano, J F; Anderson, G B

    1999-07-01

    Animals with extreme body growth frequently experience poor reproductive performance, but the cause for this association has not been clearly established. A line of mice homozygous for the high growth (hg) mutation, a mutation that has a major effect on post-weaning growth, exhibits several reproductive deficits including an abnormally high incidence of luteal failure. The objective of the present study was to investigate luteal failure in high-growth (HG) mice during pregnancy and to determine whether the cause of the apparent luteal failure resides in the ovary or the hypothalamic-pituitary unit. In HG females with a demonstrated history of infertility, progesterone injections (1 mg s.c. daily) beginning on Day 1 postcoitum (p.c.) increased the proportion of animals pregnant at Day 17 of gestation. Twice-daily injections of 100 microgram of ovine prolactin (PRL) in alkaline saline given to another group of females beginning on Day 1 p.c. increased the proportion of HG females that were pregnant on Day 6 of gestation compared with saline-injected HG females, although PRL did not increase the pregnancy rate in HG females when compared with a group of noninjected control females. When ovaries from HG females were transplanted into ovariectomized congenic C57 hosts, the C57 graft hosts displayed normal estrous cycles, and upon mating the majority of graft hosts became pregnant. In contrast, when ovaries from C57 females were transplanted into ovariectomized HG hosts, the HG graft hosts displayed normal estrous cycles, but upon mating most were unable to maintain pregnancy. These results suggest that the hypothalamic-pituitary unit of the HG female provides an inadequate signal to the ovaries to maintain pregnancy. Luteal failure in HG females may be due to insufficient PRL as required for establishment and early maintenance of the CL during pregnancy in mice.

  14. 5α-Reductase Inhibition Prevents the Luteal Phase Increase in Plasma Allopregnanolone Levels and Mitigates Symptoms in Women with Premenstrual Dysphoric Disorder.

    PubMed

    Martinez, Pedro E; Rubinow, David R; Nieman, Lynnette K; Koziol, Deloris E; Morrow, A Leslie; Schiller, Crystal E; Cintron, Dahima; Thompson, Karla D; Khine, Khursheed K; Schmidt, Peter J

    2016-03-01

    Changes in neurosteroid levels during the luteal phase of the menstrual cycle may precipitate affective symptoms. To test this hypothesis, we stabilized neurosteroid levels by administering the 5α-reductase inhibitor dutasteride to block conversion of progesterone to its neurosteroid metabolite allopregnanolone in women with premenstrual dysphoric disorder (PMDD) and in asymptomatic control women. Sixteen women with prospectively confirmed PMDD and 16 control women participated in one of two separate randomized, double-blind, placebo-controlled, cross-over trials, each lasting three menstrual cycles. After one menstrual cycle of single-blind placebo, participants were randomized to receive, for the next two menstrual cycles, either double-blind placebo or dutasteride (low-dose 0.5 mg/day in the first eight PMDD and eight control women or high-dose 2.5 mg/day in the second group of women). All women completed the daily rating form (DRF) and were evaluated in clinic during the follicular and luteal phases of each menstrual cycle. Main outcome measures were the DRF symptoms of irritability, sadness, and anxiety. Analyses were performed with SAS PROC MIXED. In the low-dose group, no significant effect of dutasteride on PMDD symptoms was observed compared with placebo (ie, symptom cyclicity maintained), and plasma allopregnanolone levels increased in women with PMDD from follicular to the luteal phases, suggesting the absence of effect of the low-dose dutasteride on 5α-reductase. In contrast, the high-dose group experienced a statistically significant reduction in several core PMDD symptoms (ie, irritability, sadness, anxiety, food cravings, and bloating) on dutasteride compared with placebo. Dutasteride had no effect on mood in controls. Stabilization of allopregnanolone levels from the follicular to the luteal phase of the menstrual cycle by blocking the conversion of progesterone to its 5α-reduced neurosteroid metabolite mitigates symptoms in PMDD. These data

  15. Relationships between thyroid hormones and serum energy metabolites with different patterns of postpartum luteal activity in high-producing dairy cows.

    PubMed

    Kafi, M; Tamadon, A; Saeb, M; Mirzaei, A; Ansari-Lari, M

    2012-08-01

    This study investigated the relationships of thyroid hormones, serum energy metabolites, reproductive parameters, milk yield and body condition score with the different patterns of postpartum luteal activity in the postpartum period. A total of 75 multiparous healthy (free of detectable reproductive disorders) Holstein dairy cows (mean peak milk yield = 56.5 ± 7.0 kg/day) were used in this study. Transrectal ultrasound scanning and blood sample collection were performed twice weekly. Serum concentrations of progesterone (P4) were measured twice weekly and beta-hydroxybutyrate (BHBA), non-esterified fatty acids, thyroxine (T4), 3,30,5-tri-iodothyronine (T3), free thyroxine (fT4) and free 3,30,5-tri-iodothyronine (fT3) were measured every 2 weeks from the 1st to the 8th week postpartum. On the basis of the serum P4 profile of the cows, 25 (33.4%) had normal luteal activity (NLA), whereas 30 (40%), 10 (13.3%), 6 (8%) and 4 (5.3%) had prolonged luteal phase (PLP), delayed first ovulation (DOV), anovulation (AOV) and short luteal phase, respectively. Serum T4 concentrations in PLP cows were higher than that in NLA cows at the 3rd week postpartum and did not change during the period of study, whereas in the NLA cows the concentrations increased (P < 0.05). Further, the least square (LS) mean of serum fT4 concentrations in the DOV and AOV cows were significantly lower than in the NLA cows during the study period (P < 0.05). In addition, the AOV cows had higher LS mean serum BHBA and T4 concentrations than the NLA cows in early weeks postpartum (P < 0.05). In conclusion, the serum thyroid hormones' profile differs in high-producing dairy cows showing PLP, AOV and DOV in comparison with the postpartum NLA cows.

  16. Decreased follicular phase gonadotropin secretion is associated with impaired estradiol and progesterone secretion during the follicular and luteal phases in normally menstruating women.

    PubMed

    Schweiger, U; Laessle, R G; Tuschl, R J; Broocks, A; Krusche, T; Pirke, K M

    1989-05-01

    We tested the hypothesis that disturbed follicular development and disturbed luteal progesterone (P4) secretion are associated with reduced gonadotropin secretion in the early follicular phase by measuring pulsatile LH and FSH secretion at that time in 53 normally menstruating women. Three groups of women were identified on the basis of serum sex steroid concentrations (measured daily throughout the cycle) and luteal phase length. Group A (n = 27) had normal ovarian hormone secretion with peak serum estradiol (E2) concentrations of 440 pmol/L or more, peak serum P4 concentrations of 19 nmol/L or more, and luteal phase length of 9 days or more. Group B (n = 16) had normal peak serum E2 values, but peak serum P4 values less than 19 nmol/L and/or luteal phase length less than 9 days. Group C (n = 10) had peak serum E2 values below 440 pmol/L. Risk factors for the disturbances found in groups B and C were exercise and/or intermittent dieting. Compared to group A, both groups B and C had reduced mean serum LH concentrations (3.1 +/- 1.5 vs. 2.3 +/- 1.4 and 2.0 +/- 1.0 IU/L; P less than 0.05) and reduced LH pulse frequencies (5.2 +/- 2.1 vs. 3.5 +/- 1.8 and 3.3 +/- 2.3 pulses/12 h; P less than 0.02). LH amplitude was similar in all 3 groups. Mean serum FSH concentrations were slightly but not significantly lower in group C. We conclude that reduced gonadotropin secretion during the follicular phase may indeed affect E2 and P4 secretion at later stages of the menstrual cycle. The patterns of alteration associated with disturbed E2 and P4 secretion in normally menstruating women are similar to those that occur in women with hypothalamic amenorrhea.

  17. Ovarian hyperstimulation syndrome prevention strategies: Luteal support strategies to optimize pregnancy success in cycles with gonadotropin-releasing hormone agonist ovulatory trigger.

    PubMed

    Engmann, Lawrence; Benadiva, Claudio

    2010-11-01

    Gonadotropin-releasing hormone agonist (GnRHa) administration for the induction of oocyte maturation during in vitro fertilization treatment is effective in the prevention of ovarian hyperstimulation syndrome (OHSS). However, some studies have reported a lower ongoing pregnancy rate after GnRHa trigger. The excellent conception rates reported in recipients receiving embryos originating from donor cycles or in women receiving frozen embryos originating from fresh cycles during which GnRHa was used to induce oocyte maturation suggest that it does not adversely affect the quality of the oocyte or embryo. A defective corpus luteum function resulting from the relatively short endogenous luteinizing hormone surge may be detrimental to endometrial receptivity. Aggressive luteal phase support and monitoring is therefore essential in view of the overwhelming evidence suggestive of abnormal luteal phase steroid profile. This may be achieved by the use of adequate estradiol and progesterone supplementation in the luteal phase and the first trimester. An alternative approach is the use of adjuvant low-dose human chorionic gonadotropin, although caution should be exercised in view of the associated risk of OHSS development.

  18. Ultrastructural and biochemical evidence for the presence of mature steroidogenic acute regulatory protein (StAR) in the cytoplasm of human luteal cells.

    PubMed

    Sierralta, Walter D; Kohen, Paulina; Castro, Olga; Muñoz, Alex; Strauss, Jerome F; Devoto, Luigi

    2005-10-20

    The distribution of the steroidogenic acute regulatory protein (StAR) inside thecal and granulosa-lutein cells of human corpus luteum (CL) was assessed by immunoelectron microscopy. We found greater levels of StAR immunolabeling in steroidogenic cells from early- and mid-than in late luteal phase CL and lower levels in cells from women treated with a GnRH antagonist in the mid-luteal phase. Immunoelectron microscopy revealed significant levels of StAR antigen in the mitochondria and in the cytoplasm of luteal cells. The 30 kDa mature StAR protein was present in both mitochondria and cytosol (post-mitochondrial) fractions from homogenates of CL at different ages, whereas cytochrome c and mitochondrial HSP70 were detected only in the mitochondrial fraction. Therefore, we hypothesized that either appreciable processing of StAR 37 kDa pre-protein occurs outside the mitochondria, or mature StAR protein is selectively released into the cytoplasm after mitochondrial processing. The presence of mature StAR in the cytoplasm is consonant with the notion that StAR acts on the outer mitochondrial membrane to effect sterol import, and that StAR may interact with other cytoplasmic proteins involved in cholesterol metabolism, including hormone sensitive lipase. PMID:16162390

  19. Wild bootstrap for quantile regression.

    PubMed

    Feng, Xingdong; He, Xuming; Hu, Jianhua

    2011-12-01

    The existing theory of the wild bootstrap has focused on linear estimators. In this note, we broaden its validity by providing a class of weight distributions that is asymptotically valid for quantile regression estimators. As most weight distributions in the literature lead to biased variance estimates for nonlinear estimators of linear regression, we propose a modification of the wild bootstrap that admits a broader class of weight distributions for quantile regression. A simulation study on median regression is carried out to compare various bootstrap methods. With a simple finite-sample correction, the wild bootstrap is shown to account for general forms of heteroscedasticity in a regression model with fixed design points.

  20. Tumor necrosis factor alpha-induced apoptosis in human neuronal cells: protection by the antioxidant N-acetylcysteine and the genes bcl-2 and crmA.

    PubMed Central

    Talley, A K; Dewhurst, S; Perry, S W; Dollard, S C; Gummuluru, S; Fine, S M; New, D; Epstein, L G; Gendelman, H E; Gelbard, H A

    1995-01-01

    Tumor necrosis factor alpha (TNF-alpha) is a candidate human immunodeficiency virus type 1-induced neurotoxin that contributes to the pathogenesis of AIDS dementia complex. We report here on the effects of exogenous TNF-alpha on SK-N-MC human neuroblastoma cells differentiated to a neuronal phenotype with retinoic acid, TNF-alpha caused a dose-dependent loss of viability and a corresponding increase in apoptosis in differentiated SK-N-MC cells but not in undifferentiated cultures. Importantly, intracellular signalling via TNF receptors, as measured by activation of the transcription factor NF-kappa B, was unaltered by retinoic acid treatment. Finally, overexpression of bcl-2 or crmA conferred resistance to apoptosis mediated by TNF-alpha, as did the addition of the antioxidant N-acetylcysteine. These results suggest that TNF-alpha induces apoptosis in neuronal cells by a pathway that involves formation of reactive oxygen intermediates and which can be blocked by specific genetic interventions. PMID:7739519

  1. Sperm apoptosis in nonpregnant luteal phase sera after in vitro fertilization as assessed by comparative genomic hybridization.

    PubMed

    Bouma, C L; Patton, W C; Jacobson, J D; King, A; Chan, P J

    2004-01-01

    Toxicity in serum has been reported in cases of recurrent spontaneous abortions and endometriosis. The null hypothesis was that serum toxicity was not involved in failed pregnancies after in vitro fertilization procedures. The objective was to expose donor sperm to pregnant versus nonpregnant patient sera and analyze for sperm DNA damaging effects using a novel comparative genomic hybridization method. Luteal phase sera (N = 21 cases) were drawn one week after embryo transfer. Colloid-washed donor sperm were incubated (48 h, 37 degrees C, 5% CO2 in air) in 0% or 50% sera. Single-stranded DNA (ssDNA) of control sperm were stained in Hoechst 33342 and hybridized to Sybr Gold-stained ssDNA of sera-treated sperm. Image analyses were performed and fluorescent intensities analyzed. Nonpregnant patient sera (57% of cases) were associated with DNA fragmentation (64.4 +/- 8.8 pixels; mean +/- S.E.M.) when compared with pregnant patient sera (106.3 +/- 8.4 pixels). There were no differences in the sera of biochemical (108.2 +/- 15.3) versus clinical pregnancy cases (105.3 +/- 11.4). The results suggest that nonpregnant patient sera contained factor(s) that cause DNA fragmentation leading to pregnancy losses.

  2. Differential effects of exogenous progesterone administration at different stages of the luteal phase on endogenous oestradiol concentration in cows.

    PubMed

    Starbuck, G R; Mann, G E

    2010-04-01

    We have investigated the effects administering exogenous progesterone, via insertion of a controlled internal drug release (CIDR) for 4 days, from either day 5 or day 12 of the oestrous cycle on plasma oestradiol concentrations. In study 1, in which progesterone was administered from day 5, measurement of plasma oestradiol in daily samples revealed a significant (p < 0.001) decrease in peripheral oestradiol concentration. In contrast, in study 2, similar administration of progesterone from day 12 had no effect on plasma oestradiol concentration. In study 3, collection of hourly samples following progesterone treatment on day 5 revealed peak progesterone concentrations within 1 h of CIDR insertion and nadir oestradiol concentrations within 4 h. The results demonstrate that treatment with progesterone early in the luteal phase causes a rapid inhibition of oestradiol secretion, while later treatment does not. While improvements in pregnancy rate following progesterone treatment at this time have traditionally been attributed to increases in progesterone, the potential involvement of decreased oestradiol secretion has often been overlooked. PMID:19144035

  3. Estrus synchronization and conception rate after a progesterone releasing intravaginal device (PRID) treatment from the early luteal phase in heifers.

    PubMed

    Kuroiwa, Takenobu; Ishibashi, Ai; Fukuda, Masaharu; Kim, Seungjoon; Tanaka, Tomomi; Kamomae, Hideo

    2005-10-01

    The objective of the present study was to evaluate estrus synchronization and conception rate after progesterone releasing intravaginal device (PRID) treatment from the early luteal phase in the presence or absence of estradiol benzoate (EB) in heifers. Heifers (n=11) were assigned randomly to two treatments; insertion of a PRID containing 1.55 g progesterone with a capsule attached including 10 mg EB (P+EB; n=6) and the PRID withdrawn the EB capsule (P-EB; n=5). The PRID was inserted into the vagina on Day 2 of the estrous cycle (Day 0 was the day of ovulation) and was left for 12 days. The proportion of heifers exhibiting standing estrus within 3 days after PRID removal was 83.3% (5/6) for the P+EB group, and 80.0% (4/5) for the P-EB group, respectively. Conception rate by artificial insemination on synchronized estrus was 80.0% (4/5) in the P+EB group, and 100% (4/4) in the P-EB treatment group, respectively. These results suggest that a PRID treatment from 2 days after ovulation for 12 days in the presence or absence of EB has an effect on the synchronization of estrus and produces a beneficial conception rate in heifers.

  4. Reduced Phase-Advance of Plasma Melatonin after Bright Morning Light in the Luteal, but not Follicular, Menstrual Cycle Phase in Premenstrual Dysphoric Disorder: An Extended Study

    PubMed Central

    Parry, Barbara L.; Meliska, Charles J.; Sorenson, Diane L.; Martínez, L. Fernando; López, Ana M.; Elliott, Jeffrey A.; Hauger, Richard L.

    2011-01-01

    We previously observed blunted phase-shift responses to morning bright light in women with Premenstrual Dysphoric Disorder (PMDD). The aim of this study was to determine if we could replicate these findings using a higher intensity, shorter duration light pulse and to compare these results with the effects of an evening bright light pulse. In 17 PMDD patients and 14 normal control (NC) subjects, we measured plasma melatonin at 30 minute intervals from 18:00–10:00 h in dim (< 30 lux) or dark conditions the night before (night 1) and after (night 3) a bright light pulse (administered on night 2) in both follicular and luteal menstrual cycle phases. The bright light (either 3,000 lux for 6 h or 6,000 lux for 3 h) was given either in the AM, 7 h after the Dim Light Melatonin Onset (DLMO) measured the previous month, or in the PM, 3 h after the DLMO. In the luteal, but not in the follicular, phase, AM light advanced melatonin offset between night 1 and night 3 significantly less in PMDD than in NC subjects. The effects of PM light were not significant, nor were there significant effects of the light pulse on melatonin measures of onset, duration, peak or area under the curve. These findings replicated our previous finding of a blunted phase-shift response to morning bright light in the luteal, but not the follicular, menstrual cycle phase in PMDD compared with NC women, using a brighter (6,000 vs. 3,000 lux) light pulse for a shorter duration (3 vs. 6 h). As the effect of PM bright light on melatonin phase-shift responses did not differ between groups or significantly alter other melatonin measures, these results suggest that in PMDD there is a luteal phase subsensitivity or an increased resistance to morning bright light cues which are critical in synchronizing human biological rhythms. The resulting circadian rhythm malsynchonization may contribute to the occurrence of luteal phase depressive symptoms in women with PMDD. PMID:21721857

  5. Effect of oestrus synchronization with PGF2α/eCG/hCG on luteal P4 synthesis in early pregnant gilts.

    PubMed

    Szymanska, M; Morawska-Pucinska, E; Krawczynski, K; Kiewisz, J; Ziecik, A J; Blitek, A

    2014-12-01

    Administration of hormones to synchronize oestrus is a useful tool in animal breeding. However, exogenous ovarian stimulation may be detrimental to reproductive function. This study was aimed to examine whether an oestrus synchronization with PGF2α/eCG/hCG could affect luteal P4 synthesis in early pregnant gilts. Corpora lutea (CLs) were collected on days 9, 12 and 16 of pregnancy from gilts with natural (n = 16) and synchronized (n = 18) oestrus and analysed for (i) the expre-ssion of steroidogenic acute regulatory protein (StAR), cytochrome P450 family 11 subfamily A polypeptide (CYP11A1), and 3β-hydroxysteroid dehydrogenase (3βHSD); (ii) the concentration of P4 in the luteal tissue and blood; and (iii) the expression of luteinizing hormone receptors (LHR) and oestrogen receptors (ERα and ERβ). Additionally, the effect of LH on P4 secretion from CL slices collected from synchronized and naturally ovulated animals has been studied in vitro. PGF2α /eCG/hCG administration increased mRNA expression of StAR, CYP11A1, 3βHSD, and LHR on day 9 and CYP11A1 and LHR on day 12 of pregnancy compared with the control group (p < 0.05). CYP11A1, 3βHSD, LHR, ERα and ERβ proteins were not affected by synchronization; only StAR protein increased in hormonally treated animals (p = 0.017). The concentration of P4 in luteal tissue was greater on day 9 (p < 0.01), but lower on day 16 (p < 0.05) in gilts with hormonally induced oestrus compared with control animals. Blood serum levels of P4 were lower in synchronized than control gilts (p < 0.001). Synchronization did not affect LH-stimulated P4 secretion from luteal slices; however, greater basal concentration of P4 in incubation medium was detected for CLs collected from synchronized than control gilts (p < 0.05). In conclusion, synchronization of oestrus with PGF2α/eCG/hCG protocol in gilts did not impair the expression of luteal P4 synthesis system, although decreased P4 concentration in the blood.

  6. Evaluating differential effects using regression interactions and regression mixture models

    PubMed Central

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This paper focuses on understanding regression mixture models, a relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their formulation, and their assumptions are compared using Monte Carlo simulations and real data analysis. The capabilities of regression mixture models are described and specific issues to be addressed when conducting regression mixtures are proposed. The paper aims to clarify the role that regression mixtures can take in the estimation of differential effects and increase awareness of the benefits and potential pitfalls of this approach. Regression mixture models are shown to be a potentially effective exploratory method for finding differential effects when these effects can be defined by a small number of classes of respondents who share a typical relationship between a predictor and an outcome. It is also shown that the comparison between regression mixture models and interactions becomes substantially more complex as the number of classes increases. It is argued that regression interactions are well suited for direct tests of specific hypotheses about differential effects and regression mixtures provide a useful approach for exploring effect heterogeneity given adequate samples and study design. PMID:26556903

  7. Control of luteal relaxin release by prostaglandin F2 alpha: differences in the sow cycle and pregnancy.

    PubMed

    Bagnell, C A; Baker, N K; McMurtry, J P; Brocht, D M; Lewis, G S

    1990-06-01

    The effect of an in vivo prostaglandin F2 alpha (PGF2 alpha) challenge in pregnant and cyclic sows was compared to determine whether PGF2 alpha-induced release of relaxin (RLX) from the corpus luteum (CL) in late pregnancy is also effective during the cycle. Ovarian venous RLX and progesterone were monitored by radioimmunoassay and RLX localized in the CL by immunohistochemistry. In Day 108 pregnant sows, infusion of PGF2 alpha (100 micrograms) into the ovarian artery resulted in an immediate and sustained rise in ovarian venous RLX with an initial decline in progesterone levels by 30 min which then returned to pretreatment levels. In Day 13 or 15 cyclic sows with functional corpora lutea (i.e., elevated progesterone), RLX was undetectable in ovarian venous blood after 100 micrograms of PGF2 alpha. Administration of PGF2 alpha via either the jugular vein or intramuscular route was also ineffective in releasing RLX from the CL of the cycle. The intensity of RLX immunostaining of the CL was similar in saline and PGF2 alpha-treated sows. These studies indicate that the control of RLX release from the sow CL differs in the estrous cycle and pregnancy.

  8. Luteal-phase support in assisted reproduction treatment: real-life practices reported worldwide by an updated website-based survey.

    PubMed

    Vaisbuch, Edi; de Ziegler, Dominique; Leong, Milton; Weissman, Ariel; Shoham, Zeev

    2014-03-01

    An updated worldwide web-based survey assessed the real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. This survey looked for changes since a former survey conducted nearly 3years earlier. The survey questions were: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data were obtained from 408 centres (82 countries) representing 284,600 IVF cycles/year. The findings were: (i) most practitioners (80% of cycles) start LPS on the day of egg collection; (ii) in >90%, a vaginal progesterone product is used (77% as a single agent and 17% in combination with i.m. progesterone), while human chorionic gonadotrophin as a single agent for LPS is not being used at all; and (iii) in 72% of cycles, LPS is administered until 8-10weeks' gestation or beyond. When compared with the initial survey, the results of this survey are encouraging as there is a clear shift towards a more unified and evidence-based approach to LPS in IVF cycles. This updated worldwide web-based survey assessed the actual real-life clinical practices regarding luteal-phase supplementation (LPS) in assisted reproduction. Specifically, this survey looked for changes since an initial survey conducted nearly 3years earlier. The survey included the following questions: If you support the luteal phase, when do you start the regimen you are using?; Which agent/route is your treatment of choice to support the luteal phase?; If you use vaginal progesterone, which formulation do you use?; and How long you continue progesterone supplementation if the patient conceived? Data from 408 centres in 82 countries representing a total of 284,600 IVF cycles/year were included. Most practitioners (80% of cycles) start LPS on the day of

  9. Linear regression in astronomy. II

    NASA Technical Reports Server (NTRS)

    Feigelson, Eric D.; Babu, Gutti J.

    1992-01-01

    A wide variety of least-squares linear regression procedures used in observational astronomy, particularly investigations of the cosmic distance scale, are presented and discussed. The classes of linear models considered are (1) unweighted regression lines, with bootstrap and jackknife resampling; (2) regression solutions when measurement error, in one or both variables, dominates the scatter; (3) methods to apply a calibration line to new data; (4) truncated regression models, which apply to flux-limited data sets; and (5) censored regression models, which apply when nondetections are present. For the calibration problem we develop two new procedures: a formula for the intercept offset between two parallel data sets, which propagates slope errors from one regression to the other; and a generalization of the Working-Hotelling confidence bands to nonstandard least-squares lines. They can provide improved error analysis for Faber-Jackson, Tully-Fisher, and similar cosmic distance scale relations.

  10. Quantile regression for climate data

    NASA Astrophysics Data System (ADS)

    Marasinghe, Dilhani Shalika

    Quantile regression is a developing statistical tool which is used to explain the relationship between response and predictor variables. This thesis describes two examples of climatology using quantile regression.Our main goal is to estimate derivatives of a conditional mean and/or conditional quantile function. We introduce a method to handle autocorrelation in the framework of quantile regression and used it with the temperature data. Also we explain some properties of the tornado data which is non-normally distributed. Even though quantile regression provides a more comprehensive view, when talking about residuals with the normality and the constant variance assumption, we would prefer least square regression for our temperature analysis. When dealing with the non-normality and non constant variance assumption, quantile regression is a better candidate for the estimation of the derivative.

  11. Fluid shear stress inhibits TNF-alpha-induced apoptosis in osteoblasts: a role for fluid shear stress-induced activation of PI3-kinase and inhibition of caspase-3

    NASA Technical Reports Server (NTRS)

    Pavalko, Fredrick M.; Gerard, Rita L.; Ponik, Suzanne M.; Gallagher, Patricia J.; Jin, Yijun; Norvell, Suzanne M.

    2003-01-01

    In bone, a large proportion of osteoblasts, the cells responsible for deposition of new bone, normally undergo programmed cell death (apoptosis). Because mechanical loading of bone increases the rate of new bone formation, we hypothesized that mechanical stimulation of osteoblasts might increase their survival. To test this hypothesis, we investigated the effects of fluid shear stress (FSS) on osteoblast apoptosis using three osteoblast cell types: primary rat calvarial osteoblasts (RCOB), MC3T3-E1 osteoblastic cells, and UMR106 osteosarcoma cells. Cells were treated with TNF-alpha in the presence of cyclohexamide (CHX) to rapidly induce apoptosis. Osteoblasts showed significant signs of apoptosis within 4-6 h of exposure to TNF-alpha and CHX, and application of FSS (12 dyne/cm(2)) significantly attenuated this TNF-alpha-induced apoptosis. FSS activated PI3-kinase signaling, induced phosphorylation of Akt, and inhibited TNF-alpha-induced activation of caspase-3. Inhibition of PI3-kinase, using LY294002, blocked the ability of FSS to rescue osteoblasts from TNF-alpha-induced apoptosis and blocked FSS-induced inhibition of caspase-3 activation in osteoblasts treated with TNF-alpha. LY294002 did not, however, prevent FSS-induced phosphorylation of Akt suggesting that activation of Akt alone is not sufficient to rescue cells from apoptosis. This result also suggests that FSS can activate Akt via a PI3-kinase-independent pathway. These studies demonstrate for the first time that application of FSS to osteoblasts in vitro results in inhibition of TNF-alpha-induced apoptosis through a mechanism involving activation of PI3-kinase signaling and inhibition of caspases. FSS-induced activation of PI3-kinase may promote cell survival through a mechanism that is distinct from the Akt-mediated survival pathway. Copyright 2002 Wiley-Liss, Inc.

  12. Evaluating Differential Effects Using Regression Interactions and Regression Mixture Models

    ERIC Educational Resources Information Center

    Van Horn, M. Lee; Jaki, Thomas; Masyn, Katherine; Howe, George; Feaster, Daniel J.; Lamont, Andrea E.; George, Melissa R. W.; Kim, Minjung

    2015-01-01

    Research increasingly emphasizes understanding differential effects. This article focuses on understanding regression mixture models, which are relatively new statistical methods for assessing differential effects by comparing results to using an interactive term in linear regression. The research questions which each model answers, their…

  13. Retro-regression--another important multivariate regression improvement.

    PubMed

    Randić, M

    2001-01-01

    We review the serious problem associated with instabilities of the coefficients of regression equations, referred to as the MRA (multivariate regression analysis) "nightmare of the first kind". This is manifested when in a stepwise regression a descriptor is included or excluded from a regression. The consequence is an unpredictable change of the coefficients of the descriptors that remain in the regression equation. We follow with consideration of an even more serious problem, referred to as the MRA "nightmare of the second kind", arising when optimal descriptors are selected from a large pool of descriptors. This process typically causes at different steps of the stepwise regression a replacement of several previously used descriptors by new ones. We describe a procedure that resolves these difficulties. The approach is illustrated on boiling points of nonanes which are considered (1) by using an ordered connectivity basis; (2) by using an ordering resulting from application of greedy algorithm; and (3) by using an ordering derived from an exhaustive search for optimal descriptors. A novel variant of multiple regression analysis, called retro-regression (RR), is outlined showing how it resolves the ambiguities associated with both "nightmares" of the first and the second kind of MRA. PMID:11410035

  14. Tumor necrosis factor alpha induces the expression of transforming growth factor alpha and the epidermal growth factor receptor in human pancreatic cancer cells.

    PubMed Central

    Schmiegel, W; Roeder, C; Schmielau, J; Rodeck, U; Kalthoff, H

    1993-01-01

    Recombinant human tumor necrosis factor (TNF)-alpha increased the expression of epidermal growth factor receptor (EGFR) mRNA and protein in all of six human pancreatic carcinoma cell lines tested. In addition, TNF-alpha increased the expression of an EGFR ligand, transforming growth factor (TGF)-alpha, at the mRNA and protein level in all cell lines. Increased expression of EGFR protein was associated with elevated steady-state EGFR mRNA levels. Nuclear run-on analysis showed that increase in EGFR mRNA was due to an increased rate of transcription. Induction of EGFR mRNA expression by TNF-alpha was abrogated by cycloheximide but occurred independently of TNF-alpha-induced production of TGF-alpha protein. Protein kinase A or Gi-type guanine nucleotide-binding proteins were not involved in this process as assessed by using appropriate stimulators and inhibitors of these signal transduction pathways. By contrast, staurosporine, an inhibitor of protein kinase C, partially inhibited, and 4-bromophenacyl bromide, a phospholipase inhibitor, completely inhibited TNF-alpha-dependent EGFR mRNA expression. The phospholipase C-specific inhibitor tricyclodecan-9-yl xanthogenate did not alter TNF-alpha-dependent EGFR mRNA expression, suggesting that phospholipase A2 is involved in the modulation of EGFR expression by TNF-alpha. The simultaneous induction of a ligand/receptor system by TNF-alpha suggests that this cytokine modulates autocrine growth-regulatory pathways in pancreatic cancer cells. Images PMID:8430098

  15. Decreased Cholesterol Uptake and Increased Liver X Receptor-Mediated Cholesterol Efflux Pathways During Prostaglandin F2 Alpha-Induced and Spontaneous Luteolysis in Sheep1

    PubMed Central

    Seto, Nickie L.; Bogan, Randy L.

    2015-01-01

    In nonprimate species, it has been well established that prostaglandin F2 alpha (PGF2alpha) initiates luteolysis. Changes in intracellular cholesterol concentrations caused by modulation of cholesterol uptake and efflux may mediate PGF2alpha-induced luteolysis. These changes in cholesterol efflux and uptake are controlled, in part, by the liver x receptors (LXR) alpha (NR1H3) and beta (NR1H2), nuclear receptors that increase expression of genes necessary for cholesterol efflux or limiting cholesterol uptake. Therefore, we hypothesized that PGF2alpha reduces expression of cholesterol uptake and increases expression of cholesterol efflux genes, mediated in part by enhanced LXR activity. To test this hypothesis, an induced luteolysis model was used whereby ewes were treated during their midluteal phase with saline or PGF2alpha and corpora lutea (CL) collected 12, 24, or 48 h later for determination of mRNA and protein concentrations by quantitative real-time PCR and Western blot analysis, respectively. As a complementary approach, CL undergoing spontaneous luteolysis were compared to midluteal phase CL. The lipoprotein receptors responsible for cholesterol uptake were significantly decreased in both luteolysis models. Expression of the LXR target gene ATP binding cassette subfamily A1 (ABCA1), an important mediator of cholesterol efflux, was significantly increased in both experimental models. Chromatin immunoprecipitation confirmed that PGF2alpha treatment resulted in enhanced NR1H3 and NR1H2 binding to the ABCA1 promoter. Qualitative changes in lipid droplet distribution were also observed following PGF2alpha treatment. These data support the hypothesis that reduced cholesterol uptake and increased efflux mediate luteolysis in sheep, which is partially controlled by PGF2alpha stimulation of LXR activity. PMID:25882703

  16. Administration of interleukin-10 at the time of priming protects Corynebacterium parvum-primed mice against LPS- and TNF-alpha-induced lethality.

    PubMed

    Smith, S R; Terminelli, C; Denhardt, G; Narula, S; Thorbecke, G J

    1996-11-01

    Several laboratories have described the protective effects of interleukin-10 (IL-10) in mouse models of lethal endotoxemia. In most of these experiments, protection was observed in normal mice that were given a lethal dose of LPS. However, we failed to observe protection with IL-10 in LPS-challenged mice that had been primed with Corynebacterium parvum (Proprionibacterium acnes). We have extended our studies with IL-10 in C. parvum-primed mice and in some cases have observed protection that appears to depend on the strength of the sensitization to C. parvum. When IL-10 was administered to mice at the time of priming, it was particularly effective in blocking sensitization, as evidenced by the inability of treated mice to mount a strong inflammatory cytokine response when subsequently challenged with LPS. Following such treatment with IL-10, C. parvum-primed mice were also protected from a subsequent lethal challenge with rMuTNF-alpha. In addition, the mice were protected against LPS- and TNF-alpha-induced lethality with a single dose of an anti-TNF-alpha or anti-IFN-gamma mAb given at the time of priming. Our results suggest that TNF-alpha and IFN-gamma are produced early after priming with C. parvum and are at least partly responsible for the enhanced sensitivity of the mice to LPS and TNF-alpha. IL-10 affords protection to the mice because of its ability to block the C. parvum-induced TNF-alpha and IFN-gamma responses. PMID:8912878

  17. Precision Efficacy Analysis for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.

    When multiple linear regression is used to develop a prediction model, sample size must be large enough to ensure stable coefficients. If the derivation sample size is inadequate, the model may not predict well for future subjects. The precision efficacy analysis for regression (PEAR) method uses a cross- validity approach to select sample sizes…

  18. Logistic Regression: Concept and Application

    ERIC Educational Resources Information Center

    Cokluk, Omay

    2010-01-01

    The main focus of logistic regression analysis is classification of individuals in different groups. The aim of the present study is to explain basic concepts and processes of binary logistic regression analysis intended to determine the combination of independent variables which best explain the membership in certain groups called dichotomous…

  19. Analysis of genes that influence sheep follicular development by different nutrition levels during the luteal phase using expression profiling.

    PubMed

    Luo, F; Jia, R; Ying, S; Wang, Z; Wang, F

    2016-06-01

    Nutrition is an important factor that regulates reproductive performance of sheep and affects follicle development. However, the correlation between nutrition and follicle development is poorly understood at the molecular level. To study its possible molecular mechanisms, we performed expression profiling of granulosa cells isolated from sheep that were fed different levels of nutrition levels during the luteal phase. To do this, ewes received a maintenance diet (M), and their estrus was synchronized by intravaginal progestogen sponges for 12 days. Ewes were randomly divided into the short-term dietary-restricted group (R; 0.5 × M) and the nutrient-supplemented group (S; 1.5 × M). RNA samples were extracted from granulosa cells. Transcriptome libraries from each group were constructed by Illumina sequencing. Among 18 468 detected genes, 170 genes were significantly differentially expressed, of which 140 genes were upregulated and 30 genes were downregulated in group S relative to group R. These genes could be candidates regulating follicular development in sheep. Gene Ontology, KEGG and clustering analyses were performed. Genes related to oocyte meiosis, such as ADCY7, were upregulated. We identified two important groups of related genes that were upregulated with improved nutrition: one group comprising the genes PTGS2, UCP2 and steroidogenic acute regulatory protein and the other group comprising interleukin-1A and interleukin-1B. The genes within each group showed similar expression patterns. Additionally, all five genes are involved in the reproduction process. Quantitative real-time PCR was performed to validate the results of expression profiling. These data in our study are an abundant genomic resource to expand the understanding of the molecular and cellular events underlying follicle development. PMID:26970339

  20. Wild bootstrap for quantile regression.

    PubMed

    Feng, Xingdong; He, Xuming; Hu, Jianhua

    2011-12-01

    The existing theory of the wild bootstrap has focused on linear estimators. In this note, we broaden its validity by providing a class of weight distributions that is asymptotically valid for quantile regression estimators. As most weight distributions in the literature lead to biased variance estimates for nonlinear estimators of linear regression, we propose a modification of the wild bootstrap that admits a broader class of weight distributions for quantile regression. A simulation study on median regression is carried out to compare various bootstrap methods. With a simple finite-sample correction, the wild bootstrap is shown to account for general forms of heteroscedasticity in a regression model with fixed design points. PMID:23049133

  1. [Regression grading in gastrointestinal tumors].

    PubMed

    Tischoff, I; Tannapfel, A

    2012-02-01

    Preoperative neoadjuvant chemoradiation therapy is a well-established and essential part of the interdisciplinary treatment of gastrointestinal tumors. Neoadjuvant treatment leads to regressive changes in tumors. To evaluate the histological tumor response different scoring systems describing regressive changes are used and known as tumor regression grading. Tumor regression grading is usually based on the presence of residual vital tumor cells in proportion to the total tumor size. Currently, no nationally or internationally accepted grading systems exist. In general, common guidelines should be used in the pathohistological diagnostics of tumors after neoadjuvant therapy. In particularly, the standard tumor grading will be replaced by tumor regression grading. Furthermore, tumors after neoadjuvant treatment are marked with the prefix "y" in the TNM classification. PMID:22293790

  2. Fungible weights in logistic regression.

    PubMed

    Jones, Jeff A; Waller, Niels G

    2016-06-01

    In this article we develop methods for assessing parameter sensitivity in logistic regression models. To set the stage for this work, we first review Waller's (2008) equations for computing fungible weights in linear regression. Next, we describe 2 methods for computing fungible weights in logistic regression. To demonstrate the utility of these methods, we compute fungible logistic regression weights using data from the Centers for Disease Control and Prevention's (2010) Youth Risk Behavior Surveillance Survey, and we illustrate how these alternate weights can be used to evaluate parameter sensitivity. To make our work accessible to the research community, we provide R code (R Core Team, 2015) that will generate both kinds of fungible logistic regression weights. (PsycINFO Database Record

  3. Alterations in luteal production of androstenedione, testosterone, and estrone, but not estradiol, during mid- and late pregnancy in pigs: effects of androgen deficiency.

    PubMed

    Grzesiak, Malgorzata; Knapczyk-Stwora, Katarzyna; Ciereszko, Renata E; Wieciech, Iwona; Slomczynska, Maria

    2014-09-15

    Recently, we have found that flutamide-induced androgen deficiency altered progesterone production in the porcine corpus luteum (CL) during mid- and late pregnancy. Herein, we tested whether flutamide administration subsequently influences androgen and estrogen metabolism in the CL of pregnancy. Pregnant gilts were treated with flutamide between Days 43 and 49 (GD50F), 83 and 89 (GD90F), or 101 and 107 (GD108F) of gestation. Corpora lutea (CLs) were collected from treated and nontreated (control) pigs. The concentrations of androstenedione (A4), testosterone (T), estrone (E1), and estradiol (E2) together with the levels of expression of mRNAs and proteins for cytochrome P450 17α-hydroxylase/c17-20 lyase (CYP17A1), 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1), cytochrome P450 aromatase (CYP19A1), and 17β-hydroxysteroid dehydrogenase type 7 (17β-HSD7) were measured in the CL of control and flutamide-treated animals. Steroidogenic enzymes were also immunolocalized in luteal tissues. The luteal concentrations of A4 and T were higher in the GD50F (P = 0.006, P = 0.03) and GD108F (P = 0.005, P = 0.035) groups, but lower in the GD90F (P = 0.004, P = 0.014) group. The E1 level was greater only in the GD90F (P = 0.03) and GD108F (P = 0.035) groups, whereas E2 concentration was not affected by flutamide treatment. Increased luteal CYP17A1 mRNA and protein expression was found in the GD50F (P = 0.002, P = 0.03) and GD108F (P = 0.0026, P = 0.03) groups, but reduced in the GD90F (P = 0.002, P = 0.03) group. mRNA of 17β-HSD1 was upregulated in the GD50F (P = 0.0005) group, but downregulated in the GD90F (P = 0.002) and GD108F (P = 0.0005) groups. In contrast, 17β-HSD1 protein expression was higher in the GD50F and GD108F (P = 0.03) groups, but lower in the GD90F (P = 0.03) group. Both CYP19A1 mRNA and protein levels were greater in the GD90F (P = 0.001, P = 0.028) and GD108F (P = 0.005, P = 0.03) groups. Neither 17β-HSD7 mRNA nor protein level were affected by

  4. Stress and the menstrual cycle: short- and long-term response to a five-day endotoxin challenge during the luteal phase in the rhesus monkey.

    PubMed

    Xiao, E; Xia-Zhang, L; Ferin, M

    1999-02-01

    Previously, we reported that in the rhesus monkey a 5-day inflammatory-like stress during the early-mid follicular phase acutely stimulates the hypothalamic-pituitary-adrenal axis and exerts effects on the hypothalamic-pituitary-gonadal axis, delays folliculogenesis and in some animals decreases luteal function in the post-treatment cycle. Because the endocrine environment at the time of the stress may influence the response to the stress, we now investigate the acute and long-term responses to a similar stress challenge during the luteal phase of the menstrual cycle, at a time of progesterone dominance. Nine monkeys with normal cycles were injected with endotoxin (lipopolysaccharide; LPS, 150 microg i.v.) twice a day for 5 days starting on days 4-8 after the LH peak. Blood samples were taken at hour 3 and hour 8 after each morning LPS injection to monitor the acute gonadotropin and cortisol responses. To verify cyclicity, menses were checked every day, and daily blood samples were taken for estradiol and progesterone measurement. Two control cycles, the LPS treatment cycle, and two post-treatment cycles were documented. Endotoxin activated the adrenal axis: mean (+/-SE) cortisol secretion was significantly increased at hour 3 after the first morning LPS injection (74.1 +/- 4.9 vs. 24.1 +/- 1.8 microg/dL in the control; P < 0.05) and remained elevated at hour 8. This response decreased progressively with time: on day 5 of LPS treatment, the cortisol level was still significantly higher than control at hour 3 (38.5 +/- 5.0 microg/dL; P < 0.05) but had returned to the control concentration by hour 8 (days 3-5 of LPS). Mean integrated progesterone through the luteal phase of the LPS treatment cycle was significantly decreased (33.5 +/- 3.3 ng/ml vs. 48.9 +/- 3.7 and 54.0 +/- 4.9 in the two control cycles; P < 0.05), but luteal phase length remained unchanged. When compared with control levels on the same day of the luteal phase, about one third of LH and FSH values

  5. Luteal 3beta-hydroxysteroid dehydrogenase and 20alpha-hydroxysteroid dehydrogenase activities in the rat corpus luteum of pseudopregnancy: Effect of the deciduoma reaction

    PubMed Central

    Clementi, Marisa A; Deis, Ricardo P; Telleria, Carlos M

    2004-01-01

    Background In the rat, the maintenance of gestation is dependent on progesterone production from the corpora lutea (CL), which are under the control of pituitary, decidual and placental hormones. The luteal metabolism of progesterone during gestation has been amply studied. However, the regulation of progesterone synthesis and degradation during pseudopregnancy (PSP), in which the CL are mainly under the control of pituitary prolactin (PRL), is not well known. The objectives of this investigation were: i) to study the luteal metabolism of progesterone during PSP by measuring the activities of the enzymes 3beta-hydroxysteroid dehydrogenase (3betaHSD), involved in progesterone biosynthesis, and that of 20alpha-hydroxysteroid dehydrogenase (20alphaHSD), involved in progesterone catabolism; and ii) to determine the role of decidualization on progesterone metabolism in PSP. Methods PSP was induced mechanically at 10:00 h on the estrus of 4-day cycling Wistar rats, and the stimulus for decidualization was provided by scratching the uterus on day 4 of PSP. 3betaHSD and 20alphaHSD activities were measured in the CL isolated from ovaries of PSP rats using a spectrophotometric method. Serum concentrations of progesterone, PRL, androstenedione, and estradiol were measured by radioimmunoassay (RIA). Results The PSP stage induced mechanically in cycling rats lasted 11.3 ± 0.09 days (n = 14). Serum progesterone concentration was high until day 10 of PSP, and declined thereafter. Serum PRL concentration was high on the first days of PSP but decreased significantly from days 6 to 9, having minimal values on days 10 and 11. Luteal 3betaHSD activities were elevated until day 6 of PSP, after which they progressively declined, reaching minimal values at the end of PSP. Luteal 20alphaHSD activities were very low until day 9, but abruptly increased at the end of PSP. When the deciduoma was induced by scratching the uterus of pseudopregnant animals on day 4 (PSP+D), PSP was extended to

  6. Duration of luteal support (DOLS) with progesterone pessaries to improve the success rates in assisted conception: study protocol for a randomized controlled trial

    PubMed Central

    2012-01-01

    Background Luteal support with progesterone is necessary for successful implantation of the embryo following egg collection and embryo transfer in an in-vitro fertilization (IVF) cycle. Progesterone has been used for as little as 2 weeks and for as long as 12 weeks of gestation. The optimal length of treatment is unresolved at present and it remains unclear how long to treat women receiving luteal supplementation. Design The trial is a prospective, randomized, double-blind, placebo-controlled trial to investigate the effect of the duration of luteal support with progesterone in IVF cycles. Following 2 weeks standard treatment and a positive biochemical pregnancy test, this randomized control trial will allocate women to a supplementary 8 weeks treatment with vaginal progesterone or 8 weeks placebo. Further studies would be required to investigate whether additional supplementation with progesterone is beneficial in early pregnancy. Discussion Currently at the Hewitt Centre, approximately 32.5% of women have a positive biochemical pregnancy test 2 weeks after embryo transfer. It is this population that is eligible for trial entry and randomization. Once the patient has confirmed a positive urinary pregnancy test they will be invited to join the trial. Once the consent form has been completed by the patient a trial prescription sheet will be sent to pharmacy with a stated collection time. The patient can then be randomized and the drugs dispensed according to pharmacy protocol. A blood sample will then be drawn for measurement of baseline hormone levels (progesterone, estradiol, free beta-human chorionic gonadotrophin, pregnancy-associated plasma protein-A, Activin A, Inhibin A and Inhibin B). The primary outcome measure is the proportion of all randomized women that continue successfully to a viable pregnancy (at least one fetus with fetal heart rate >100 beats/minute) on transabdominal/transvaginal ultrasound at 10 weeks post embryo transfer/12 weeks gestation

  7. Evidence for multiple uterine modulators of rabbit luteal function: the effect of hysterectomy during pseudopregnancy in the estrogen-treated rabbit.

    PubMed

    Miller, J B; McLean, M P

    1987-04-01

    Previous studies show that hysterectomy on Day 1 of pseudopregnancy prolongs serum progesterone secretion in estrogen-treated pseudopregnant rabbits. These studies were undertaken to determine the day of pseudopregnancy when uterine factors are released to alter luteal function. When hysterectomies were performed on either Day 5, 8, 10, or 13 of pseudopregnancy, serum progesterone concentrations were greater than 10 ng/ml between Days 18 and 27 of pseudopregnancy compared to levels of approximately 4 ng/ml in sham-hysterectomized rabbits on these same days. In contrast, serum progesterone levels were not elevated when hysterectomies were performed on Day 11 of pseudopregnancy and were only partially maintained when hysterectomies were performed on Day 12 of pseudopregnancy. Twice daily injections of prolactin (1.5 mg, s.c.) between Days 1 and 33 of pseudopregnancy were unable to mimic the effect of estradiol in the hysterectomized rabbit. Twice daily injections of indomethacin (8 mg/kg, s.c.) between Days 6 and 23 of pseudopregnancy lowered uterine and luteal prostaglandin F2 alpha levels approximately 10-fold on Day 24 of pseudopregnancy but did not maintain progesterone secretion. Serum cholesterol levels were not altered by hysterectomy on any day and were thus not related to the maintenance of progesterone production. These results suggest that the uterus produces both inhibitory and stimulatory factors that effect luteal progesterone secretion. First, an inhibitor is released between Days 10 and 11 of pseudopregnancy in estrogen-treated rabbits that prevents the rabbit corpus luteum from responding to estradiol.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Effects of different five-day progesterone-based synchronization protocols on the estrous response and follicular/luteal dynamics in dairy cows.

    PubMed

    López-Gatius, Fernando; López-Helguera, Irene; De Rensis, Fabio; Garcia-Ispierto, Irina

    2015-01-01

    This study compared the responses shown by lactating dairy cows to four different P4-based protocols for AI at estrus. Cows with no estrous signs 96 h after progesterone intravaginal device (PRID) removal were subjected to fixed-time AI (FTAI), and their data were also included in the study. In Experiment I, follicular/luteal and endometrial dynamics were assessed every 12 h from the beginning of treatment until AI. The estrous response was examined in Experiment II, and fertility was assessed in both experiments. The protocols consisted of a PRID fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone (GnRH), equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I (40 cows), animals receiving GnRH at the start of treatment showed a significantly higher ovulation rate during the PRID insertion period while estrus was delayed. In Experiment II (351 cows), according to the odds ratios, cows showing luteal activity at the time of treatment were less likely to show estrus than cows with no signs of luteal activity. Treatment affected the estrous response and the interval from PRID removal to estrus but did not affect conception rates 28-34 days post AI. Primiparous cows displayed a better estrous response than multiparous cows. Our findings reveal acceptable results of 5-day P4-based protocols for AI at estrus in high-producing dairy cows. Time from treatment to estrus emerged as a good guide for FTAI after a 5-day P4-based synchronization protocol.

  9. Effects of different five-day progesterone-based synchronization protocols on the estrous response and follicular/luteal dynamics in dairy cows

    PubMed Central

    LÓPEZ-GATIUS, Fernando; LÓPEZ-HELGUERA, Irene; DE RENSIS, Fabio; GARCIA-ISPIERTO, Irina

    2015-01-01

    This study compared the responses shown by lactating dairy cows to four different P4-based protocols for AI at estrus. Cows with no estrous signs 96 h after progesterone intravaginal device (PRID) removal were subjected to fixed-time AI (FTAI), and their data were also included in the study. In Experiment I, follicular/luteal and endometrial dynamics were assessed every 12 h from the beginning of treatment until AI. The estrous response was examined in Experiment II, and fertility was assessed in both experiments. The protocols consisted of a PRID fitted for five days, along with the administration of different combinations of gonadotropin releasing hormone (GnRH), equine chorionic gonadotropin and a single or double dose (24 h apart) of prostaglandin F2α. In Experiment I (40 cows), animals receiving GnRH at the start of treatment showed a significantly higher ovulation rate during the PRID insertion period while estrus was delayed. In Experiment II (351 cows), according to the odds ratios, cows showing luteal activity at the time of treatment were less likely to show estrus than cows with no signs of luteal activity. Treatment affected the estrous response and the interval from PRID removal to estrus but did not affect conception rates 28–34 days post AI. Primiparous cows displayed a better estrous response than multiparous cows. Our findings reveal acceptable results of 5-day P4-based protocols for AI at estrus in high-producing dairy cows. Time from treatment to estrus emerged as a good guide for FTAI after a 5-day P4-based synchronization protocol. PMID:26211922

  10. Expression of calbindin-D9k and vitamin D receptor in the uterus of Egyptian buffalo during follicular and luteal phases.

    PubMed

    Emam, Mahmoud Abdelghaffar; Abouelroos, Mahmoud E A; Gad, Fatma A

    2016-06-01

    Uteri of mature Egyptian buffalo cows (5-10 years old) were collected at follicular (n=12) and luteal (n=16) phases of estrous cycle to investigate the expression of calbindin-D9k (CaPB-9k) and vitamin D receptor (VDR). This study was done using avidin-biotin immunohistochemistry method. In addition, blood levels of calcium (Ca), vitamin D3 (Vit D), estrogen (E2) and progesterone (P4) were measured. The immunohistochemical findings restricted the expressions of CaBP-9k and VDR to the luminal and glandular epithelia of the endometrium implicating the importance of CaBP-9K and VDR in the function of endometrial epithelium, especially the glandular one, in order to prepare a receptive uterus. On the other hand, the myometrium did not express CaBP-9k or VDR that denies the potential role of CaBP-9k and VDR in the uterine contractility during the estrous cycle of Egyptian buffalo. All of Ca, Vit D, and P4 blood levels significantly (P<0.05) increased during luteal phase however, blood level of E2 significantly (P<0.05) increased during follicular phase. The expressions of CaBP-9k and VDR in the uterus of Egyptian buffalo were significantly (P<0.05) higher during luteal (P4 dominant) phase than during the follicular (E2 dominant) phase indicating that P4 up-regulates the expressions of CaBP-9k and VDR. In view of these observations, this study represents the first characterization of CaBP-9K and VDR expression in the uterus of Egyptian buffalo and suggests the pivotal role of CaBP-9k and VDR in the uterine receptivity. Furthermore, it demonstrates the regulatory role of P4 for expressions of CaBP-9k and VDR in buffalo uterus. PMID:27142230

  11. Practical Session: Simple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Two exercises are proposed to illustrate the simple linear regression. The first one is based on the famous Galton's data set on heredity. We use the lm R command and get coefficients estimates, standard error of the error, R2, residuals …In the second example, devoted to data related to the vapor tension of mercury, we fit a simple linear regression, predict values, and anticipate on multiple linear regression. This pratical session is an excerpt from practical exercises proposed by A. Dalalyan at EPNC (see Exercises 1 and 2 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_4.pdf).

  12. Impact of Buserelin Acetate or hCG Administration on the Day of First Artificial Insemination on Subsequent Luteal Profile and Conception Rate in Murrah Buffalo (Bubalus bubalis).

    PubMed

    Pandey, A K; Ghuman, Sps; Dhaliwal, G S; Agarwal, S K; Phogat, J B

    2016-08-01

    This study was designed to investigate the impact of buserelin acetate (BA) or human chorionic gonadotropin (hCG) administration on the day of first artificial insemination (AI) on subsequent luteal profile (diameter of corpus luteum (CL) and plasma progesterone) and conception rate in Murrah buffalo. The present experiment was carried out at two locations in 117 buffalo that were oestrus-synchronized using cloprostenol (500 μg) administered (i.m.) 11 days apart followed by AI during standing oestrus. Based on treatment (i.m.) at the time of AI, buffalo were randomly categorized (n = 39 in each group) into control (isotonic saline solution, 5 ml), dAI-BA (buserelin acetate, 20 μg) and dAI-hCG (hCG, 3000 IU) group. Out of these, 14 buffalo of each group were subjected to ovarian ultrasonography on the day of oestrus to monitor the preovulatory follicle and on days 5, 12, 16 and 21 post-ovulation to monitor CL diameter. On the day of each sonography, jugular vein blood samples were collected for the estimation of progesterone concentrations. All the buffalo (n = 117) were confirmed for pregnancy on day 40 post-ovulation. The conception rate was better (p < 0.05) in dAI-BA (51.3%) and dAI-hCG (66.7%) groups as compared to their control counterparts (30.8%). Furthermore, the buffalo of dAI-hCG group had improved (p < 0.05) luteal profile, whereas the buffalo of dAI-BA group failed (p > 0.05) to exhibit stimulatory impact of treatment on luteal profile when compared to control group. In brief, buserelin acetate or hCG treatment on the day of first AI leads to an increase in conception rate; however, an appreciable impact on post-ovulation luteal profile was observed only in hCG-treated Murrah buffalo. PMID:27170495

  13. Prostaglandin F2alpha stimulates the Raf/MEK1/mitogen-activated protein kinase signaling cascade in bovine luteal cells.

    PubMed

    Chen, D B; Westfall, S D; Fong, H W; Roberson, M S; Davis, J S

    1998-09-01

    Upon binding to its G protein-coupled transmembrane receptors, the actions of PGF2alpha on the corpus luteum are initiated by the phospholipase C/diacylglycerol-inositol 1,4,5-trisphosphate (InsP3)/Ca2+-protein kinase C (PKC) pathway. However, little is known about the downstream intracellular signaling events that can lead to transcriptional activation in response to PGF2alpha. The present study was conducted to examine the involvement of the mitogen-activated protein kinase (MAPK) signaling cascade in the corpus luteum. Three isoforms of the Raf family of oncoprotein kinases (A-Raf, B-Raf, and Raf-1 or c-Raf) were detected in bovine luteal cells. Raf-1 and B-Raf, but not A-Raf, were activated by PGF2alpha (1 microM) and the pharmacological PKC activator phorbol myristate acetate (PMA, 20 nM). Kinetic analysis revealed that PGF2alpha rapidly and transiently activated Raf-1. In vitro protein kinase assays demonstrated that activation of Raf-1 and B-Raf resulted in the phosphorylation and activation of MAPK kinase (MEK1), which subsequently phosphorylated p42mapk. As determined by hyperphosphorylation, tyrosine phosphorylation, and enzymatic activity, p42mapk and p44mapk were rapidly and transiently activated by both PGF2alpha (1 microM) and PMA (20 nM). Additionally, both PGF2alpha (1 microM) and PMA (20 nM) stimulated phosphorylation of Raf-1, MEK1, and p42mapk in 32P-labeled cells. Our data demonstrate that PGF2alpha activates the Raf/MEK1/p42/44mapk signaling cascade in bovine luteal cells and that the actions of PGF2alpha are mimicked by the PKC activator PMA. Activation of the Raf/MEK1/MAPK signaling cascade by PGF2alpha in luteal cells provides a mechanism to transduce signals initiated by PGF2alpha receptors on the cell surface into the nucleus. Activation of the Raf/MEK1/MAPK signaling cascade may be associated with transcriptional activation of luteal genes possessing activator protein-1-binding sites.

  14. Multiple Regression and Its Discontents

    ERIC Educational Resources Information Center

    Snell, Joel C.; Marsh, Mitchell

    2012-01-01

    Multiple regression is part of a larger statistical strategy originated by Gauss. The authors raise questions about the theory and suggest some changes that would make room for Mandelbrot and Serendipity.

  15. Regression methods for spatial data

    NASA Technical Reports Server (NTRS)

    Yakowitz, S. J.; Szidarovszky, F.

    1982-01-01

    The kriging approach, a parametric regression method used by hydrologists and mining engineers, among others also provides an error estimate the integral of the regression function. The kriging method is explored and some of its statistical characteristics are described. The Watson method and theory are extended so that the kriging features are displayed. Theoretical and computational comparisons of the kriging and Watson approaches are offered.

  16. Wrong Signs in Regression Coefficients

    NASA Technical Reports Server (NTRS)

    McGee, Holly

    1999-01-01

    When using parametric cost estimation, it is important to note the possibility of the regression coefficients having the wrong sign. A wrong sign is defined as a sign on the regression coefficient opposite to the researcher's intuition and experience. Some possible causes for the wrong sign discussed in this paper are a small range of x's, leverage points, missing variables, multicollinearity, and computational error. Additionally, techniques for determining the cause of the wrong sign are given.

  17. Basis Selection for Wavelet Regression

    NASA Technical Reports Server (NTRS)

    Wheeler, Kevin R.; Lau, Sonie (Technical Monitor)

    1998-01-01

    A wavelet basis selection procedure is presented for wavelet regression. Both the basis and the threshold are selected using cross-validation. The method includes the capability of incorporating prior knowledge on the smoothness (or shape of the basis functions) into the basis selection procedure. The results of the method are demonstrated on sampled functions widely used in the wavelet regression literature. The results of the method are contrasted with other published methods.

  18. Regression Discontinuity Designs in Epidemiology

    PubMed Central

    Moscoe, Ellen; Mutevedzi, Portia; Newell, Marie-Louise; Bärnighausen, Till

    2014-01-01

    When patients receive an intervention based on whether they score below or above some threshold value on a continuously measured random variable, the intervention will be randomly assigned for patients close to the threshold. The regression discontinuity design exploits this fact to estimate causal treatment effects. In spite of its recent proliferation in economics, the regression discontinuity design has not been widely adopted in epidemiology. We describe regression discontinuity, its implementation, and the assumptions required for causal inference. We show that regression discontinuity is generalizable to the survival and nonlinear models that are mainstays of epidemiologic analysis. We then present an application of regression discontinuity to the much-debated epidemiologic question of when to start HIV patients on antiretroviral therapy. Using data from a large South African cohort (2007–2011), we estimate the causal effect of early versus deferred treatment eligibility on mortality. Patients whose first CD4 count was just below the 200 cells/μL CD4 count threshold had a 35% lower hazard of death (hazard ratio = 0.65 [95% confidence interval = 0.45–0.94]) than patients presenting with CD4 counts just above the threshold. We close by discussing the strengths and limitations of regression discontinuity designs for epidemiology. PMID:25061922

  19. Luteal phase support with estradiol and progesterone versus progesterone alone in GnRH antagonist ICSI cycles: a randomized controlled study.

    PubMed

    Ismail Madkour, Wael A; Noah, Bassel; Abdel Hamid, Amr M S; Zaheer, Hena; Al-Bahr, Awatif; Shaeer, Mahmoud; Moawad, Ashraf

    2016-06-01

    In vitro fertilization (IVF) cycles are associated with a defective luteal phase. Although progesterone supplementation to treat this problem is standard practice, estrogen addition is debatable. Our aim was to compare pregnancy outcomes in 220 patients undergoing antagonist intracytoplasmic sperm injection (ICSI) cycles protocol. The patients were randomly assigned into two equal groups to receive either vaginal progesterone alone (90 mg once daily) starting on the day of oocyte retrieval for up to 12 weeks if pregnancy occurred or estradiol addition (2 mg twice daily) starting on the same day and continuing up to seven weeks (foetal viability scan). Primary outcomes were pregnancy and ongoing pregnancy rates per embryo transfer. Secondary outcomes were implantation and early pregnancy loss rates. Pregnancy rates showed no significant difference between group 1 (39.09%) and 2 (43.63%) (p value = 0.3). Similarly, both groups were comparable regarding ongoing pregnancy rate (32.7% group 1 and 36.3% group 2, p value = 0.1). Implantation rates showed no difference between group 1 (19.25%) and group 2 (23.44%) (p value = 0.2). Early pregnancy loss rates were comparable, with 6.3% and 7.2% in groups 1 and 2, respectively, (p value = 0.4). In conclusion, the addition of 4 mg estrogen daily to progesterone for luteal support in antagonist ICSI cycles is not beneficial for pregnancy outcome. PMID:27434094

  20. Interpretation of Standardized Regression Coefficients in Multiple Regression.

    ERIC Educational Resources Information Center

    Thayer, Jerome D.

    The extent to which standardized regression coefficients (beta values) can be used to determine the importance of a variable in an equation was explored. The beta value and the part correlation coefficient--also called the semi-partial correlation coefficient and reported in squared form as the incremental "r squared"--were compared for variables…

  1. Regressive Evolution in Astyanax Cavefish

    PubMed Central

    Jeffery, William R.

    2013-01-01

    A diverse group of animals, including members of most major phyla, have adapted to life in the perpetual darkness of caves. These animals are united by the convergence of two regressive phenotypes, loss of eyes and pigmentation. The mechanisms of regressive evolution are poorly understood. The teleost Astyanax mexicanus is of special significance in studies of regressive evolution in cave animals. This species includes an ancestral surface dwelling form and many con-specific cave-dwelling forms, some of which have evolved their recessive phenotypes independently. Recent advances in Astyanax development and genetics have provided new information about how eyes and pigment are lost during cavefish evolution; namely, they have revealed some of the molecular and cellular mechanisms involved in trait modification, the number and identity of the underlying genes and mutations, the molecular basis of parallel evolution, and the evolutionary forces driving adaptation to the cave environment. PMID:19640230

  2. Laplace regression with censored data.

    PubMed

    Bottai, Matteo; Zhang, Jiajia

    2010-08-01

    We consider a regression model where the error term is assumed to follow a type of asymmetric Laplace distribution. We explore its use in the estimation of conditional quantiles of a continuous outcome variable given a set of covariates in the presence of random censoring. Censoring may depend on covariates. Estimation of the regression coefficients is carried out by maximizing a non-differentiable likelihood function. In the scenarios considered in a simulation study, the Laplace estimator showed correct coverage and shorter computation time than the alternative methods considered, some of which occasionally failed to converge. We illustrate the use of Laplace regression with an application to survival time in patients with small cell lung cancer.

  3. Survival Data and Regression Models

    NASA Astrophysics Data System (ADS)

    Grégoire, G.

    2014-12-01

    We start this chapter by introducing some basic elements for the analysis of censored survival data. Then we focus on right censored data and develop two types of regression models. The first one concerns the so-called accelerated failure time models (AFT), which are parametric models where a function of a parameter depends linearly on the covariables. The second one is a semiparametric model, where the covariables enter in a multiplicative form in the expression of the hazard rate function. The main statistical tool for analysing these regression models is the maximum likelihood methodology and, in spite we recall some essential results about the ML theory, we refer to the chapter "Logistic Regression" for a more detailed presentation.

  4. Interquantile Shrinkage in Regression Models

    PubMed Central

    Jiang, Liewen; Wang, Huixia Judy; Bondell, Howard D.

    2012-01-01

    Conventional analysis using quantile regression typically focuses on fitting the regression model at different quantiles separately. However, in situations where the quantile coefficients share some common feature, joint modeling of multiple quantiles to accommodate the commonality often leads to more efficient estimation. One example of common features is that a predictor may have a constant effect over one region of quantile levels but varying effects in other regions. To automatically perform estimation and detection of the interquantile commonality, we develop two penalization methods. When the quantile slope coefficients indeed do not change across quantile levels, the proposed methods will shrink the slopes towards constant and thus improve the estimation efficiency. We establish the oracle properties of the two proposed penalization methods. Through numerical investigations, we demonstrate that the proposed methods lead to estimations with competitive or higher efficiency than the standard quantile regression estimation in finite samples. Supplemental materials for the article are available online. PMID:24363546

  5. Prostaglandin E2 downregulates TNF-alpha-induced production of matrix metalloproteinase-1 in HCS-2/8 chondrocytes by inhibiting Raf-1/MEK/ERK cascade through EP4 prostanoid receptor activation.

    PubMed

    Fushimi, Kazunari; Nakashima, Shigeru; You, Fukka; Takigawa, Masaharu; Shimizu, Katsuji

    2007-02-15

    Matrix metalloproteinase-1 (MMP-1, collagenase-1) plays a pivotal role in the process of joint destruction in degenerative joint diseases. We have examined the regulation of MMP-1 production in human chondrocytic HCS-2/8 cells stimulated by tumor necrosis factor-alpha (TNF-alpha). In response to TNF-alpha, MMP-1 is induced and actively released from HCS-2/8 cells. The induction of MMP-1 expression correlates with activation of ERK1/2, MEK, and Raf-1, and is potently prevented by U0126, a selective inhibitor of MEK1/2 activation. In contrast, SB203580, a selective p38 mitogen-activated protein kinases (MAPK) inhibitor, had no effects on TNF-alpha-induced MMP-1 release. A serine/threonine kinase, Akt was not activated in TNF-alpha-stimulated HCS-2/8 cells. TNF-alpha stimulated the production of PGE(2) in addition to MMP-1 in HCS-2/8 cells. Exogenously added PGE(2) potently inhibited TNF-alpha-induced both MMP-1 production and activation of ERK1/2. The effects of PGE(2) were mimicked by ONO-AE1-329, a selective EP4 receptor agonist but not by butaprost, a selective EP2 agonist. In contrast, blockade of endogenously produced PGE(2) signaling by ONO-AE3-208, a selective EP4 receptor antagonist, enhanced TNF-alpha-induced MMP-1 production. Furthermore, the suppression of MMP-1 production by exogenously added PGE(2) was reversed by ONO-AE3-208. Activation of EP4 receptor resulted in cAMP-mediated phosphorylation of Raf-1 on Ser259, a negative regulatory site, and blocked activation of Raf-1/MEK/ERK cascade. Taken together, these findings indicate that Raf-1/MEK/ERK signaling pathway plays a crucial role in the production of MMP-1 in HCS-2/8 cells in response to TNF-alpha, and that the produced PGE(2) downregulates the expression of MMP-1 by blockage of TNF-alpha-induced Raf-1 activation through EP4-PGE(2) receptor activation.

  6. [Is regression of atherosclerosis possible?].

    PubMed

    Thomas, D; Richard, J L; Emmerich, J; Bruckert, E; Delahaye, F

    1992-10-01

    Experimental studies have shown the regression of atherosclerosis in animals given a cholesterol-rich diet and then given a normal diet or hypolipidemic therapy. Despite favourable results of clinical trials of primary prevention modifying the lipid profile, the concept of atherosclerosis regression in man remains very controversial. The methodological approach is difficult: this is based on angiographic data and requires strict standardisation of angiographic views and reliable quantitative techniques of analysis which are available with image processing. Several methodologically acceptable clinical coronary studies have shown not only stabilisation but also regression of atherosclerotic lesions with reductions of about 25% in total cholesterol levels and of about 40% in LDL cholesterol levels. These reductions were obtained either by drugs as in CLAS (Cholesterol Lowering Atherosclerosis Study), FATS (Familial Atherosclerosis Treatment Study) and SCOR (Specialized Center of Research Intervention Trial), by profound modifications in dietary habits as in the Lifestyle Heart Trial, or by surgery (ileo-caecal bypass) as in POSCH (Program On the Surgical Control of the Hyperlipidemias). On the other hand, trials with non-lipid lowering drugs such as the calcium antagonists (INTACT, MHIS) have not shown significant regression of existing atherosclerotic lesions but only a decrease on the number of new lesions. The clinical benefits of these regression studies are difficult to demonstrate given the limited period of observation, relatively small population numbers and the fact that in some cases the subjects were asymptomatic. The decrease in the number of cardiovascular events therefore seems relatively modest and concerns essentially subjects who were symptomatic initially. The clinical repercussion of studies of prevention involving a single lipid factor is probably partially due to the reduction in progression and anatomical regression of the atherosclerotic plaque

  7. Correlation Weights in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.; Jones, Jeff A.

    2010-01-01

    A general theory on the use of correlation weights in linear prediction has yet to be proposed. In this paper we take initial steps in developing such a theory by describing the conditions under which correlation weights perform well in population regression models. Using OLS weights as a comparison, we define cases in which the two weighting…

  8. Weighting Regressions by Propensity Scores

    ERIC Educational Resources Information Center

    Freedman, David A.; Berk, Richard A.

    2008-01-01

    Regressions can be weighted by propensity scores in order to reduce bias. However, weighting is likely to increase random error in the estimates, and to bias the estimated standard errors downward, even when selection mechanisms are well understood. Moreover, in some cases, weighting will increase the bias in estimated causal parameters. If…

  9. Multiple Regression: A Leisurely Primer.

    ERIC Educational Resources Information Center

    Daniel, Larry G.; Onwuegbuzie, Anthony J.

    Multiple regression is a useful statistical technique when the researcher is considering situations in which variables of interest are theorized to be multiply caused. It may also be useful in those situations in which the researchers is interested in studies of predictability of phenomena of interest. This paper provides an introduction to…

  10. Cactus: An Introduction to Regression

    ERIC Educational Resources Information Center

    Hyde, Hartley

    2008-01-01

    When the author first used "VisiCalc," the author thought it a very useful tool when he had the formulas. But how could he design a spreadsheet if there was no known formula for the quantities he was trying to predict? A few months later, the author relates he learned to use multiple linear regression software and suddenly it all clicked into…

  11. Ridge Regression for Interactive Models.

    ERIC Educational Resources Information Center

    Tate, Richard L.

    1988-01-01

    An exploratory study of the value of ridge regression for interactive models is reported. Assuming that the linear terms in a simple interactive model are centered to eliminate non-essential multicollinearity, a variety of common models, representing both ordinal and disordinal interactions, are shown to have "orientations" that are favorable to…

  12. Quantile Regression with Censored Data

    ERIC Educational Resources Information Center

    Lin, Guixian

    2009-01-01

    The Cox proportional hazards model and the accelerated failure time model are frequently used in survival data analysis. They are powerful, yet have limitation due to their model assumptions. Quantile regression offers a semiparametric approach to model data with possible heterogeneity. It is particularly powerful for censored responses, where the…

  13. Logistic regression: a brief primer.

    PubMed

    Stoltzfus, Jill C

    2011-10-01

    Regression techniques are versatile in their application to medical research because they can measure associations, predict outcomes, and control for confounding variable effects. As one such technique, logistic regression is an efficient and powerful way to analyze the effect of a group of independent variables on a binary outcome by quantifying each independent variable's unique contribution. Using components of linear regression reflected in the logit scale, logistic regression iteratively identifies the strongest linear combination of variables with the greatest probability of detecting the observed outcome. Important considerations when conducting logistic regression include selecting independent variables, ensuring that relevant assumptions are met, and choosing an appropriate model building strategy. For independent variable selection, one should be guided by such factors as accepted theory, previous empirical investigations, clinical considerations, and univariate statistical analyses, with acknowledgement of potential confounding variables that should be accounted for. Basic assumptions that must be met for logistic regression include independence of errors, linearity in the logit for continuous variables, absence of multicollinearity, and lack of strongly influential outliers. Additionally, there should be an adequate number of events per independent variable to avoid an overfit model, with commonly recommended minimum "rules of thumb" ranging from 10 to 20 events per covariate. Regarding model building strategies, the three general types are direct/standard, sequential/hierarchical, and stepwise/statistical, with each having a different emphasis and purpose. Before reaching definitive conclusions from the results of any of these methods, one should formally quantify the model's internal validity (i.e., replicability within the same data set) and external validity (i.e., generalizability beyond the current sample). The resulting logistic regression model

  14. Associations of Serum Levels of Sex Hormones in Follicular and Luteal Phases of the Menstrual Cycle with Breast Tissue Characteristics in Young Women

    PubMed Central

    Taylor, Monica; Dunn, Sheila; Martin, Lisa; Chavez, Sonia; Stanitz, Greg; Huszti, Ella; Minkin, Salomon; Boyd, Norman

    2016-01-01

    Background In previous work in young women aged 15–30 years we measured breast water and fat using MR and obtained blood for hormone assays on the same day in the follicular phase of the menstrual cycle. Only serum growth hormone levels and sex hormone binding globulin (SHBG) were significantly associated with percent breast water after adjustment for covariates. The sex hormones estradiol, progesterone and testosterone were not associated with percent water in the breast in the follicular phase of the menstrual cycle. In the present study we have examined the association of percent breast water with serum levels of sex hormones in both follicular and luteal phase of the menstrual cycle. Methods In 315 healthy white Caucasian young women aged 15–30 with regular menstrual cycles who had not used oral contraceptives or other hormones in the previous 6 months, we used MR to determine percent breast water, and obtained blood samples for hormone assays within 10 days of the onset of the most recent menstrual cycle (follicular phase) of the cycle on the same day as the MR scan, and a second blood sample on days 19–24 of the cycle. Serum progesterone levels of > = 5 mmol/L in days 19–24 were used to define the 225 subjects with ovulatory menstrual cycles, whose data are the subject of the analyses shown here. Results SHBG was positively associated with percent water in both follicular and luteal phases of the menstrual cycle. Total and free estradiol and total and free testosterone were not associated with percent water in the follicular phase, but in young women with ovulatory cycles, were all negatively associated with percent water in the luteal phase. Conclusions Our results from young women aged 15–30 years add to the evidence that the extent of fibroglandular tissue in the breast that is reflected in both mammographic density and breast water is associated positively with higher serum levels of SHBG, but not with higher levels of sex hormones. PMID

  15. Changes in the ovarian dynamics and endocrine profiles in goats treated with a progesterone antagonist during the early luteal phase of the estrous cycle.

    PubMed

    Suganuma, Chiho; Kuroiwa, Takenobu; Tanaka, Tomomi; Kamomae, Hideo

    2007-10-01

    The aim of the present study was to determine the physiological role of endogenous progesterone in the regulation of ovarian dynamics, gonadotropin and progesterone secretion during the early luteal phase in the goat. Cycling Shiba goats received subcutaneously a vehicle (control group, n=5) or 50 mg of RU486 (RU486 group, n=4) daily from 1 to 7 days after ovulation (day 0) determined by transrectal ultrasonography. Ovarian dynamics were monitored by the ultrasonography and blood samples were collected daily until the subsequent ovulation for analysis of progesterone, luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion. Blood samples were also collected at 10 min intervals for 6 h on day 3 and day 7 for the analysis of pulsatile patterns of LH and FSH. The LH pulse frequency was significantly (P<0.05) higher in the RU486 group than in the control group on day 7 (4.8+/-1.1 pulses/6 h versus 1.2+/-0.4 pulses/6 h). The shape of the FSH pulses was unclear on day 3 and day 7 in both groups and the overall means of FSH concentration for 6 h on day 3 and day 7 were not significantly different between the RU486 and the control groups. The pattern of daily FSH concentrations showed a wave-like fluctuation in both groups. There was no significant difference in the inter-peak intervals of the wave-like pattern of daily FSH secretion between the RU486 and the control groups (4.1+/-0.6 days versus 4.5+/-0.6 days). The maximum diameter of the largest follicle that grew from day 1 to day 7 in the RU486 group tended to be greater than that in control goats (6.4+/-0.8 mm versus 5.0+/-0.8 mm, P=0.050), whereas no significant difference was detected in the size of the corpus luteum and progesterone concentrations between the control and RU486 groups on almost all days during the treatment period. These results indicate that the rise of the progesterone concentration suppresses the pulsatile LH secretion and follicular growth, whereas progesterone has no

  16. Effects of an antiprogesterone (RU486) on the hypothalamic-hypophyseal-ovarian-endometrial axis during the luteal phase of the menstrual cycle.

    PubMed

    Garzo, V G; Liu, J; Ulmann, A; Baulieu, E; Yen, S S

    1988-03-01

    The impact of the antiprogesterone RU486 [17 beta-hydroxy-11 beta-(4-dimethylaminophenyl) 17 alpha-(1-propynyl)estra- 4,9-dien-3-one] on the hypothalamic-pituitary-ovarian-endometrial axis was examined in normal cycling women during the mid (MLP)- and late (LLP) luteal phases. During the MLP, 10 women received 3 mg/kg RU486 for 3 days. During the LLP, a single dose of 600 mg RU486 was administered to 4 women, and in another 4 women a single dose of 3 mg/kg was given during corpus luteum rescue by hCG. Longitudinal studies with daily and frequent blood samples (every 10 min for 10 h) were conducted during 3 consecutive cycles (control-treatment-recovery). During the MLP, RU486-induced uterine bleeding occurred in all 10 women 36-72 h after the first dose. No histological evidence of endometrial breakdown was found in endometrial biopsies taken 12-24 h before the onset of bleeding. Significant decreases in LH secretion (P less than 0.001) and LH pulse amplitude (P less than 0.006) and blunted pituitary responses to GnRH (P less than 0.01) were evident by the last treatment day, but LH pulse frequency did not change. Complete luteolysis occurred in 2 of the 10 women. Incomplete luteolysis occurred in 8 women and was associated with an initial decline of serum estradiol (P less than 0.001), but not progesterone levels, followed by rebound increases (P less than 0.001) in LH, estradiol, and progesterone levels 3 days later, which may have reversed the luteolytic processes and prolonged corpus luteum function. Spontaneous luteolysis ensued 3-5 days later with the onset of second episodes of uterine bleeding. For serum FSH, an early rise occurred during the luteal phase in advance of the onset of the second episodes of uterine bleeding. This rise may have resulted in early follicle recruitment and accounted for the shorter duration of the follicular phase during recovery cycles. During the LLP, the single RU486 dose resulted in significant decreases in LH pulse amplitude

  17. Regression Verification Using Impact Summaries

    NASA Technical Reports Server (NTRS)

    Backes, John; Person, Suzette J.; Rungta, Neha; Thachuk, Oksana

    2013-01-01

    Regression verification techniques are used to prove equivalence of syntactically similar programs. Checking equivalence of large programs, however, can be computationally expensive. Existing regression verification techniques rely on abstraction and decomposition techniques to reduce the computational effort of checking equivalence of the entire program. These techniques are sound but not complete. In this work, we propose a novel approach to improve scalability of regression verification by classifying the program behaviors generated during symbolic execution as either impacted or unimpacted. Our technique uses a combination of static analysis and symbolic execution to generate summaries of impacted program behaviors. The impact summaries are then checked for equivalence using an o-the-shelf decision procedure. We prove that our approach is both sound and complete for sequential programs, with respect to the depth bound of symbolic execution. Our evaluation on a set of sequential C artifacts shows that reducing the size of the summaries can help reduce the cost of software equivalence checking. Various reduction, abstraction, and compositional techniques have been developed to help scale software verification techniques to industrial-sized systems. Although such techniques have greatly increased the size and complexity of systems that can be checked, analysis of large software systems remains costly. Regression analysis techniques, e.g., regression testing [16], regression model checking [22], and regression verification [19], restrict the scope of the analysis by leveraging the differences between program versions. These techniques are based on the idea that if code is checked early in development, then subsequent versions can be checked against a prior (checked) version, leveraging the results of the previous analysis to reduce analysis cost of the current version. Regression verification addresses the problem of proving equivalence of closely related program

  18. Changes in the proteome of functional and regressing corpus luteum during pregnancy and lactation in the rat.

    PubMed

    González-Fernández, Raquel; Martínez-Galisteo, Emilia; Gaytán, Francisco; Bárcena, José Antonio; Sánchez-Criado, José Eugenio

    2008-07-01

    The corpus luteum (CL) is an exquisitely regulated transitory endocrine gland necessary for the onset and maintenance of pregnancy in mammals. Most of the data on the mechanisms of CL differentiation at the molecular level come from genomic studies, but direct protein data are scarce. Here we have undertaken a differential expression proteomic approach to identify, in an unbiased way, those proteins whose levels change significantly in the rat CL as it evolves from functionality during pregnancy to regression after parturition. Moreover, we have compared the regressing CL with the newly formed functional CL that coexist during lactation under the same endocrine environment. We have defined a "proteomic signature" of CL functionality, which is constituted by a set of 24 proteins with a few differences between pregnancy and lactation. Most of these markers are new and are involved in microtubule assembly, retinoic acid transport, and Raf kinase signaling cascade; 10 are enzymes that define a ketogenic metabolic landscape, demonstrating, for the first time, the prevalence of de novo cholesterol synthesis in luteal cells. The "proteomic signature of regression," on the other hand, is composed of nine proteins, one of which is 20alpha-hydroxysteroid dehydrogenase and two, ferritin and gamma-actin, are new. The discovery of unpredictable new actors in the differentiation process of CL reported here will contribute to new hypotheses that explain the complex female reproductive function at the protein level. It will also open new doors to research on each identified protein by relating them to cellular differentiation.

  19. Quantile Regression With Measurement Error

    PubMed Central

    Wei, Ying; Carroll, Raymond J.

    2010-01-01

    Regression quantiles can be substantially biased when the covariates are measured with error. In this paper we propose a new method that produces consistent linear quantile estimation in the presence of covariate measurement error. The method corrects the measurement error induced bias by constructing joint estimating equations that simultaneously hold for all the quantile levels. An iterative EM-type estimation algorithm to obtain the solutions to such joint estimation equations is provided. The finite sample performance of the proposed method is investigated in a simulation study, and compared to the standard regression calibration approach. Finally, we apply our methodology to part of the National Collaborative Perinatal Project growth data, a longitudinal study with an unusual measurement error structure. PMID:20305802

  20. Precision and Recall for Regression

    NASA Astrophysics Data System (ADS)

    Torgo, Luis; Ribeiro, Rita

    Cost sensitive prediction is a key task in many real world applications. Most existing research in this area deals with classification problems. This paper addresses a related regression problem: the prediction of rare extreme values of a continuous variable. These values are often regarded as outliers and removed from posterior analysis. However, for many applications (e.g. in finance, meteorology, biology, etc.) these are the key values that we want to accurately predict. Any learning method obtains models by optimizing some preference criteria. In this paper we propose new evaluation criteria that are more adequate for these applications. We describe a generalization for regression of the concepts of precision and recall often used in classification. Using these new evaluation metrics we are able to focus the evaluation of predictive models on the cases that really matter for these applications. Our experiments indicate the advantages of the use of these new measures when comparing predictive models in the context of our target applications.

  1. The luteotrophic function of galectin-1 by binding to the glycans on vascular endothelial growth factor receptor-2 in bovine luteal cells

    PubMed Central

    SANO, Masahiro; HASHIBA, Kazuhisa; NIO-KOBAYASHI, Junko; OKUDA, Kiyoshi

    2015-01-01

    The corpus luteum (CL) is a temporary endocrine gland producing a large amount of progesterone, which is essential for the establishment and maintenance of pregnancy. Galectin-1 is a β-galactose-binding protein that can modify functions of membrane glycoproteins and is expressed in the CL of mice and women. However, the physiological role of galectin-1 in the CL is unclear. In the present study, we investigated the expression and localization of galectin-1 in the bovine CL and the effect of galectin-1 on cultured luteal steroidogenic cells (LSCs) with special reference to its binding to the glycans on vascular endothelial growth factor receptor-2 (VEGFR-2). Galectin-1 protein was highly expressed at the mid and late luteal stages in the membrane fraction of bovine CL tissue and was localized to the surface of LSCs in a carbohydrate-dependent manner. Galectin-1 increased the viability in cultured LSCs. However, the viability of LSCs was decreased by addition of β-lactose, a competitive carbohydrate inhibitor of galectin-1 binding activity. VEGFR-2 protein, like galectin-1, is also highly expressed in the mid CL, and it was modified by multi-antennary glycans, which can be recognized by galectin-1. An overlay assay using biotinylated galectin-1 revealed that galectin-1 directly binds to asparagine-linked glycans (N-glycans) on VEGFR-2. Enhancement of LSC viability by galectin-1 was suppressed by a selective inhibitor of VEGFR-2. The overall findings suggest that galectin-1 plays a role as a survival factor in the bovine CL, possibly by binding to N-glycans on VEGFR-2. PMID:26155753

  2. A phenotypical approach to the effects of production traits, parturition, puerperium and body condition on commencement of luteal activity in high yielding dairy cows.

    PubMed

    Boldt, Ariane; Becker, Frank; Martin, Gunter; Nürnberg, Gerd; Römer, Anke; Kanitz, Wilhelm

    2015-06-01

    The interval from calving to commencement of luteal activity (CLA) was determined by progesterone measurements from milk samples obtained once a week until the 14th week post-partum in 513 German Holstein cows in first to third parity. Milk samples were analyzed by an "on-farm" device (eProCheck(®), Minitüb, Germany) and simultaneously by RIA. The objective of this study was to examine the effect of milk yield, protein content and body condition of a cow on the CLA post-partum. Milk progesterone concentrations of "on-farm" measurements correlated with measurements done by the RIA-method significantly (r=0.72; P<0.001). Within the analyzed herd the interval from calving until the first rise of progesterone averaged 5.6±2.4 weeks. The 100-days milk yield was not associated with CLA. Cows with a milk protein content at 1st milk recording of ≤3.5% revealed first luteal activity 1.3±0.3 weeks later than cows that had a content of >3.75% protein (P<0.01). Furthermore cows with assisted calving or dystocia presented significantly later CLA than cows which required no help during the calving process (P<0.05). The change in back fat thickness from 1st to 2nd milk recording had a significant influence on CLA (P<0.05). In conclusion the phenotypic impact of milk yield on fertility cannot be confirmed regarding to CLA. The negative energy balance after calving, caused by the high milk yields, is more detrimental for the cyclical activity as was shown by the parameters milk protein content and change in BFT.

  3. Ovariectomy during the luteal phase influences secretion of prolactin, growth hormone, and insulin-like growth factor-I in the bitch.

    PubMed

    Lee, W M; Kooistra, H S; Mol, J A; Dieleman, S J; Schaefers-Okkens, A C

    2006-07-15

    A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs of pseudopregnancy. The sharp decrease of the plasma progesterone concentration was accompanied by decreased basal plasma concentrations of GH and IGF-I and a rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile fashion both prior to and after ovariectomy. The mean basal plasma GH concentration was significantly higher before ovariectomy than on days 1 and 7 after ovariectomy. The mean area under the curve above the zero level (AUC(0)) for GH was significantly higher before than at 7 days after ovariectomy. The mean area under the curve above basal level (AUC(b)) and the frequency of GH pulses at 7 days after ovariectomy were significantly higher than before and 1 day after ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC(0) for PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid-luteal phase stops progesterone-induced GH release from the mammary gland, as evidenced by the lowering of basal plasma GH levels, the recurrence of GH pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of plasma progesterone concentration is probably a primary cause of a prolonged increase in PRL secretion. These observations underscore the importance of similar, albeit less abrupt, hormonal changes in the cyclical physiological alterations in the mammary

  4. A randomized, controlled trial comparing the efficacy and safety of aqueous subcutaneous progesterone with vaginal progesterone for luteal phase support of in vitro fertilization

    PubMed Central

    Baker, Valerie L.; Jones, Christopher A.; Doody, Kevin; Foulk, Russell; Yee, Bill; Adamson, G. David; Cometti, Barbara; DeVane, Gary; Hubert, Gary; Trevisan, Silvia; Hoehler, Fred; Jones, Clarence; Soules, Michael

    2014-01-01

    STUDY QUESTION Is the ongoing pregnancy rate with a new aqueous formulation of subcutaneous progesterone (Prolutex®) non-inferior to vaginal progesterone (Endometrin®) when used for luteal phase support of in vitro fertilization? SUMMARY ANSWER In the per-protocol (PP) population, the ongoing pregnancy rates per oocyte retrieval at 12 weeks of gestation were comparable between Prolutex and Endometrin (41.6 versus 44.4%), with a difference between groups of −2.8% (95% confidence interval (CI) −9.7, 4.2), consistent with the non-inferiority of subcutaneous progesterone for luteal phase support. WHAT IS KNOWN ALREADY Luteal phase support has been clearly demonstrated to improve pregnancy rates in women undergoing in vitro fertilization (IVF). Because of the increased risk of ovarian hyperstimulation syndrome associated with the use of hCG, progesterone has become the treatment of choice for luteal phase support. STUDY DESIGN, SIZE, DURATION This prospective, open-label, randomized, controlled, parallel-group, multicentre, two-arm, non-inferiority study was performed at eight fertility clinics. A total of 800 women, aged 18–42 years, with a BMI of ≤30 kg/m2, with <3 prior completed assisted reproductive technology (ART) cycles, exhibiting baseline (Days 2–3) FSH of ≤15 IU/L and undergoing IVF at 8 centres (seven private, one academic) in the USA, were enrolled from January 2009 through June 2011. PARTICIPANTS/MATERIALS, SETTING, METHODS In total, 800 women undergoing IVF were randomized after retrieval of at least three oocytes to an aqueous preparation of progesterone administered subcutaneously (25 mg daily) or vaginal progesterone (100 mg bid daily). Randomization was performed to enrol 100 patients at each site using a randomization list that was generated with Statistical Analysis Software (SAS®). If a viable pregnancy occurred, progesterone treatment was continued up to 12 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE Using a PP analysis

  5. Regression analysis of cytopathological data

    SciTech Connect

    Whittemore, A.S.; McLarty, J.W.; Fortson, N.; Anderson, K.

    1982-12-01

    Epithelial cells from the human body are frequently labelled according to one of several ordered levels of abnormality, ranging from normal to malignant. The label of the most abnormal cell in a specimen determines the score for the specimen. This paper presents a model for the regression of specimen scores against continuous and discrete variables, as in host exposure to carcinogens. Application to data and tests for adequacy of model fit are illustrated using sputum specimens obtained from a cohort of former asbestos workers.

  6. Multiatlas Segmentation as Nonparametric Regression

    PubMed Central

    Awate, Suyash P.; Whitaker, Ross T.

    2015-01-01

    This paper proposes a novel theoretical framework to model and analyze the statistical characteristics of a wide range of segmentation methods that incorporate a database of label maps or atlases; such methods are termed as label fusion or multiatlas segmentation. We model these multiatlas segmentation problems as nonparametric regression problems in the high-dimensional space of image patches. We analyze the nonparametric estimator’s convergence behavior that characterizes expected segmentation error as a function of the size of the multiatlas database. We show that this error has an analytic form involving several parameters that are fundamental to the specific segmentation problem (determined by the chosen anatomical structure, imaging modality, registration algorithm, and label-fusion algorithm). We describe how to estimate these parameters and show that several human anatomical structures exhibit the trends modeled analytically. We use these parameter estimates to optimize the regression estimator. We show that the expected error for large database sizes is well predicted by models learned on small databases. Thus, a few expert segmentations can help predict the database sizes required to keep the expected error below a specified tolerance level. Such cost-benefit analysis is crucial for deploying clinical multiatlas segmentation systems. PMID:24802528

  7. Variable Selection in ROC Regression

    PubMed Central

    2013-01-01

    Regression models are introduced into the receiver operating characteristic (ROC) analysis to accommodate effects of covariates, such as genes. If many covariates are available, the variable selection issue arises. The traditional induced methodology separately models outcomes of diseased and nondiseased groups; thus, separate application of variable selections to two models will bring barriers in interpretation, due to differences in selected models. Furthermore, in the ROC regression, the accuracy of area under the curve (AUC) should be the focus instead of aiming at the consistency of model selection or the good prediction performance. In this paper, we obtain one single objective function with the group SCAD to select grouped variables, which adapts to popular criteria of model selection, and propose a two-stage framework to apply the focused information criterion (FIC). Some asymptotic properties of the proposed methods are derived. Simulation studies show that the grouped variable selection is superior to separate model selections. Furthermore, the FIC improves the accuracy of the estimated AUC compared with other criteria. PMID:24312135

  8. Practical Session: Multiple Linear Regression

    NASA Astrophysics Data System (ADS)

    Clausel, M.; Grégoire, G.

    2014-12-01

    Three exercises are proposed to illustrate the simple linear regression. In the first one investigates the influence of several factors on atmospheric pollution. It has been proposed by D. Chessel and A.B. Dufour in Lyon 1 (see Sect. 6 of http://pbil.univ-lyon1.fr/R/pdf/tdr33.pdf) and is based on data coming from 20 cities of U.S. Exercise 2 is an introduction to model selection whereas Exercise 3 provides a first example of analysis of variance. Exercises 2 and 3 have been proposed by A. Dalalyan at ENPC (see Exercises 2 and 3 of http://certis.enpc.fr/~dalalyan/Download/TP_ENPC_5.pdf).

  9. Expression of factors associated with apoptosis in the porcine corpus luteum throughout the luteal phase of the estrous cycle and early pregnancy: their possible involvement in acquisition of luteolytic sensitivity.

    PubMed

    Przygrodzka, E; Witek, K J; Kaczmarek, M M; Andronowska, A; Ziecik, A J

    2015-03-01

    The studies on the acquisition of luteolytic sensitivity have been focused mainly on molecular changes induced in the luteal tissue after treatment with exogenous PGF2α or on physiological changes occurring during the estrous cycle. The comparison of changes leading to the acquisition of luteolytic sensitivity after Day 12 of the estrous cycle and corresponding days of pregnancy has not been investigated in the pig. The present study was undertaken to evaluate (1) apoptosis measured as the proportions of early apoptotic, late apoptotic, and viable cells; (2) expression of factors involved in the extrinsic (TNFA/TNFα, TNFRSF1A/TNFR1, TNFRSF1B/TNFR2, FAS/Fas, and FASLG/FasL) and intrinsic (CASP3/Casp3, TP53/p-53, BAX/Bax, and BCL2/Bcl-2) apoptotic pathways, with two components of the activating protein-1 complex, i.e., FOS/Fos and JUN/Jun and IFNG/IFNγ; and (3) concentrations of luteal and blood plasma progesterone (P4) throughout the luteal phase of the estrous cycle and early pregnancy. Corpora lutea (CL) were collected postmortem on Days 8, 10, 12, and 14 of the estrous cycle and the corresponding days of pregnancy. The luteal tissue was subjected to RNA and/or protein isolation and disaggregation of CL cells followed by flow cytometry analysis aimed to determine apoptotic changes. Luteal and blood plasma P4 concentrations decreased on Day 14 of the estrous cycle versus pregnancy (P < 0.05 and P < 0.001, respectively). A significant increase in the number of early apoptotic cells and a decrease in the number of viable cells were observed on Day 14 of the estrous cycle (P < 0.001 and P < 0.05, respectively). Increase (P < 0.05) of TNFA messenger RNA (mRNA) level coincided with that of IFNG on Day 12 of the estrous cycle but not on the corresponding day of pregnancy. The content of FAS mRNA and protein increased on Day 14 of the estrous cycle versus pregnancy (P < 0.05). The mRNA expression of CASP3, BCL-2 and BAX was unchanged in cyclic and pregnant

  10. Expression of luteal estrogen receptor, interleukin-1, and apoptosis-associated genes after PGF2alpha administration in rabbits at different stages of pseudopregnancy.

    PubMed

    Maranesi, M; Zerani, M; Lilli, L; Dall'Aglio, C; Brecchia, G; Gobbetti, A; Boiti, C

    2010-08-01

    The dynamic expression for estrogen receptor subtype-1 (ESR1), interleukin-1beta (IL1B), and apoptosis-associated genes, as well as nitric oxide synthase activity, were examined in corpora lutea (CL) of rabbits after prostaglandin F(2alpha) (PGF(2alpha)) administration on either day 4 or day 9 of pseudopregnancy. By reverse transcriptase polymerase chain reaction, the steady-state level of ESR1 transcript was lower (P < 0.01) and that of anti-apoptotic B-cell CLL/lymphoma 2 (BCL2) -like 1 (BCL2L1) was greater in day 4 (P < 0.01) than in day 9 CL. Western blot analysis revealed that BCL2-associated X protein (BAX) abundance was greater in day 4 (P < 0.01) than in day 9 CL, whereas BCL2L1 protein was undetectable at both luteal stages. After PGF(2alpha), ESR1 transcript decreased (P < 0.01) in day 9 CL, whereas IL1B mRNA showed a transitory increase (P < 0.01) at both stages. The pro-apoptotic tumor protein p53 (TP53) gene had diminished (P < 0.01) on day 4 and on day 9 after a transitory increase (P < 0.01), whereas the BAX/BCL2L1 expression ratio increased (P < 0.01) in day 9 CL 24 h after treatment. Following PGF(2alpha), TP53 protein increased (P < 0.01) at both luteal stages, and BAX decreased (P < 0.01) in day 4 CL but increased (P < 0.01) 24 h later in day 9 CL; BCL2L1 became detectable 6 h later in day 4 CL. Nitric oxide synthase activity temporarily increased (P < 0.01) following PGF(2alpha). These findings suggest that PGF(2alpha) regulates luteolysis by ESR1 mRNA down-regulation and modulation of pro- and anti-apoptotic pathways in CL that have acquired a luteolytic capacity.

  11. The Expression Pattern of microRNAs in Granulosa Cells of Subordinate and Dominant Follicles during the Early Luteal Phase of the Bovine Estrous Cycle

    PubMed Central

    Gebremedhn, Samuel; Sahadevan, Sudeep; Hossain, MD Munir; Rings, Franca; Hoelker, Michael; Tholen, Ernst; Neuhoff, Christiane; Looft, Christian; Schellander, Karl; Tesfaye, Dawit

    2014-01-01

    This study aimed to investigate the miRNA expression patterns in granulosa cells of subordinate (SF) and dominant follicle (DF) during the early luteal phase of the bovine estrous cycle. For this, miRNA enriched total RNA isolated from granulosa cells of SF and DF obtained from heifers slaughtered at day 3 and day 7 of the estrous cycle was used for miRNAs deep sequencing. The results revealed that including 17 candidate novel miRNAs, several known miRNAs (n = 291–318) were detected in SF and DF at days 3 and 7 of the estrous cycle of which 244 miRNAs were common to all follicle groups. The let-7 families, bta-miR-10b, bta-miR-26a, bta-miR-99b and bta-miR-27b were among abundantly expressed miRNAs in both SF and DF at both days of the estrous cycle. Further analysis revealed that the expression patterns of 16 miRNAs including bta-miR-449a, bta-miR-449c and bta-miR-222 were differentially expressed between the granulosa cells of SF and DF at day 3 of the estrous cycle. However, at day 7 of the estrous cycle, 108 miRNAs including bta-miR-409a, bta-miR-383 and bta-miR-184 were differentially expressed between the two groups of granulosa cell revealing the presence of distinct miRNA expression profile changes between the two follicular stages at day 7 than day 3 of the estrous cycle. In addition, unlike the SF, marked temporal miRNA expression dynamics was observed in DF groups between day 3 and 7 of the estrous cycle. Target gene prediction and pathway analysis revealed that major signaling associated with follicular development including Wnt signaling, TGF-beta signaling, oocyte meiosis and GnRH signaling were affected by differentially expressed miRNAs. Thus, this study highlights the miRNA expression patterns of granulosa cells in subordinate and dominant follicles that could be associated with follicular recruitment, selection and dominance during the early luteal phase of the bovine estrous cycle. PMID:25192015

  12. Semiparametric regression during 2003–2007*

    PubMed Central

    Ruppert, David; Wand, M.P.; Carroll, Raymond J.

    2010-01-01

    Semiparametric regression is a fusion between parametric regression and nonparametric regression that integrates low-rank penalized splines, mixed model and hierarchical Bayesian methodology – thus allowing more streamlined handling of longitudinal and spatial correlation. We review progress in the field over the five-year period between 2003 and 2007. We find semiparametric regression to be a vibrant field with substantial involvement and activity, continual enhancement and widespread application. PMID:20305800

  13. Developmental Regression in Autism Spectrum Disorders

    ERIC Educational Resources Information Center

    Rogers, Sally J.

    2004-01-01

    The occurrence of developmental regression in autism is one of the more puzzling features of this disorder. Although several studies have documented the validity of parental reports of regression using home videos, accumulating data suggest that most children who demonstrate regression also demonstrated previous, subtle, developmental differences.…

  14. Building Regression Models: The Importance of Graphics.

    ERIC Educational Resources Information Center

    Dunn, Richard

    1989-01-01

    Points out reasons for using graphical methods to teach simple and multiple regression analysis. Argues that a graphically oriented approach has considerable pedagogic advantages in the exposition of simple and multiple regression. Shows that graphical methods may play a central role in the process of building regression models. (Author/LS)

  15. Regression Analysis by Example. 5th Edition

    ERIC Educational Resources Information Center

    Chatterjee, Samprit; Hadi, Ali S.

    2012-01-01

    Regression analysis is a conceptually simple method for investigating relationships among variables. Carrying out a successful application of regression analysis, however, requires a balance of theoretical results, empirical rules, and subjective judgment. "Regression Analysis by Example, Fifth Edition" has been expanded and thoroughly…

  16. Bayesian Unimodal Density Regression for Causal Inference

    ERIC Educational Resources Information Center

    Karabatsos, George; Walker, Stephen G.

    2011-01-01

    Karabatsos and Walker (2011) introduced a new Bayesian nonparametric (BNP) regression model. Through analyses of real and simulated data, they showed that the BNP regression model outperforms other parametric and nonparametric regression models of common use, in terms of predictive accuracy of the outcome (dependent) variable. The other,…

  17. Standards for Standardized Logistic Regression Coefficients

    ERIC Educational Resources Information Center

    Menard, Scott

    2011-01-01

    Standardized coefficients in logistic regression analysis have the same utility as standardized coefficients in linear regression analysis. Although there has been no consensus on the best way to construct standardized logistic regression coefficients, there is now sufficient evidence to suggest a single best approach to the construction of a…

  18. Streamflow forecasting using functional regression

    NASA Astrophysics Data System (ADS)

    Masselot, Pierre; Dabo-Niang, Sophie; Chebana, Fateh; Ouarda, Taha B. M. J.

    2016-07-01

    Streamflow, as a natural phenomenon, is continuous in time and so are the meteorological variables which influence its variability. In practice, it can be of interest to forecast the whole flow curve instead of points (daily or hourly). To this end, this paper introduces the functional linear models and adapts it to hydrological forecasting. More precisely, functional linear models are regression models based on curves instead of single values. They allow to consider the whole process instead of a limited number of time points or features. We apply these models to analyse the flow volume and the whole streamflow curve during a given period by using precipitations curves. The functional model is shown to lead to encouraging results. The potential of functional linear models to detect special features that would have been hard to see otherwise is pointed out. The functional model is also compared to the artificial neural network approach and the advantages and disadvantages of both models are discussed. Finally, future research directions involving the functional model in hydrology are presented.

  19. Estimating equivalence with quantile regression

    USGS Publications Warehouse

    Cade, B.S.

    2011-01-01

    Equivalence testing and corresponding confidence interval estimates are used to provide more enlightened statistical statements about parameter estimates by relating them to intervals of effect sizes deemed to be of scientific or practical importance rather than just to an effect size of zero. Equivalence tests and confidence interval estimates are based on a null hypothesis that a parameter estimate is either outside (inequivalence hypothesis) or inside (equivalence hypothesis) an equivalence region, depending on the question of interest and assignment of risk. The former approach, often referred to as bioequivalence testing, is often used in regulatory settings because it reverses the burden of proof compared to a standard test of significance, following a precautionary principle for environmental protection. Unfortunately, many applications of equivalence testing focus on establishing average equivalence by estimating differences in means of distributions that do not have homogeneous variances. I discuss how to compare equivalence across quantiles of distributions using confidence intervals on quantile regression estimates that detect differences in heterogeneous distributions missed by focusing on means. I used one-tailed confidence intervals based on inequivalence hypotheses in a two-group treatment-control design for estimating bioequivalence of arsenic concentrations in soils at an old ammunition testing site and bioequivalence of vegetation biomass at a reclaimed mining site. Two-tailed confidence intervals based both on inequivalence and equivalence hypotheses were used to examine quantile equivalence for negligible trends over time for a continuous exponential model of amphibian abundance. ?? 2011 by the Ecological Society of America.

  20. Insulin resistance: regression and clustering.

    PubMed

    Yoon, Sangho; Assimes, Themistocles L; Quertermous, Thomas; Hsiao, Chin-Fu; Chuang, Lee-Ming; Hwu, Chii-Min; Rajaratnam, Bala; Olshen, Richard A

    2014-01-01

    In this paper we try to define insulin resistance (IR) precisely for a group of Chinese women. Our definition deliberately does not depend upon body mass index (BMI) or age, although in other studies, with particular random effects models quite different from models used here, BMI accounts for a large part of the variability in IR. We accomplish our goal through application of Gauss mixture vector quantization (GMVQ), a technique for clustering that was developed for application to lossy data compression. Defining data come from measurements that play major roles in medical practice. A precise statement of what the data are is in Section 1. Their family structures are described in detail. They concern levels of lipids and the results of an oral glucose tolerance test (OGTT). We apply GMVQ to residuals obtained from regressions of outcomes of an OGTT and lipids on functions of age and BMI that are inferred from the data. A bootstrap procedure developed for our family data supplemented by insights from other approaches leads us to believe that two clusters are appropriate for defining IR precisely. One cluster consists of women who are IR, and the other of women who seem not to be. Genes and other features are used to predict cluster membership. We argue that prediction with "main effects" is not satisfactory, but prediction that includes interactions may be. PMID:24887437

  1. Fully Regressive Melanoma: A Case Without Metastasis.

    PubMed

    Ehrsam, Eric; Kallini, Joseph R; Lebas, Damien; Khachemoune, Amor; Modiano, Philippe; Cotten, Hervé

    2016-08-01

    Fully regressive melanoma is a phenomenon in which the primary cutaneous melanoma becomes completely replaced by fibrotic components as a result of host immune response. Although 10 to 35 percent of cases of cutaneous melanomas may partially regress, fully regressive melanoma is very rare; only 47 cases have been reported in the literature to date. AH of the cases of fully regressive melanoma reported in the literature were diagnosed in conjunction with metastasis on a patient. The authors describe a case of fully regressive melanoma without any metastases at the time of its diagnosis. Characteristic findings on dermoscopy, as well as the absence of melanoma on final biopsy, confirmed the diagnosis. PMID:27672418

  2. Developmental regression in autism spectrum disorder

    PubMed Central

    Al Backer, Nouf Backer

    2015-01-01

    The occurrence of developmental regression in autism spectrum disorder (ASD) is one of the most puzzling phenomena of this disorder. A little is known about the nature and mechanism of developmental regression in ASD. About one-third of young children with ASD lose some skills during the preschool period, usually speech, but sometimes also nonverbal communication, social or play skills are also affected. There is a lot of evidence suggesting that most children who demonstrate regression also had previous, subtle, developmental differences. It is difficult to predict the prognosis of autistic children with developmental regression. It seems that the earlier development of social, language, and attachment behaviors followed by regression does not predict the later recovery of skills or better developmental outcomes. The underlying mechanisms that lead to regression in autism are unknown. The role of subclinical epilepsy in the developmental regression of children with autism remains unclear. PMID:27493417

  3. Combined progesterone (IM + V) versus vaginal progesterone for luteal support in cleavage-stage embryo transfer cycles of good prognosis patients.

    PubMed

    Pabuccu, E G; Pabuccu, R; Evliyaoglu Ozdegirmenci, O; Bostancı Durmus, A; Keskin, M

    2016-01-01

    Many reports led to the consensus on the use of progesterone (P) for luteal-phase support. Vaginal P application is the method of choice due to its simplicity and high patient convenience but is hampered by application difficulties and personal or cultural aversions. Inappropriate vaginal P use may alter successful implantation, leading physicians to consider alternate P application routes. A worldwide survey revealed that intramuscular plus vaginal P (combined P) is the method used in nearly one-third of in vitro fertilization (IVF) cycles, particularly in Asia and North America; unfortunately, the outcomes of this approach have not been clearly elucidated. In the current analysis, we evaluated any additional benefit of short course parenteral P in addition to vaginal P capsules during a specific period in terms of implantation, pregnancy rates, miscarriages and ectopic pregnancies in cleavage stage embryo transfer (ET) cycles of good-prognosis patients. Despite significantly higher implantation rates in the combined arm, clinical and ongoing pregnancies were comparable in both groups, whereas a trend toward increased pregnancy rates was observed with combined support. The available data are too limited to draw conclusions.

  4. Effect of increasing maximal aerobic exercise on serum gonadal hormones and alpha-fetoprotein in the luteal phase of professional female soccer players.

    PubMed

    Otağ, Aynur; Hazar, Muhsin; Otağ, İlhan; Beyleroğlu, Malik

    2016-03-01

    [Purpose] The performance of female athletes during their menstrual period has attracted the attention of researchers for many years. It is known that the menstrual period changes with exercise. Alpha-fetoprotein (AFP) is an oncofetal protein. In this study, the effect of maximal aerobic exercise in the luteal phase on some hormones and AFP in female athletes was researched. [Subjects and Methods] Twelve volunteers and healthy female footballers with normal menstrual cycles volunteered for this study as subjects. All the participants performed a shuttle run test. Blood samples were taken before, after, and one hour after exercise. Serum AFP, estrogen, progesterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) values were measured using an auto analyzer and original kits. Heart rate measurements were performed before and after the exercise. [Results] AFP activity had significantly decreased after 1 h of recovery from the exercise in the female soccer players, and estrogen and LH activity had significantly increased immediately after the exercise. Progesterone activity had significantly decreased immediately after the exercise. FSH values had significantly increased immediately after the exercise. [Conclusion] The results of the present study show there were significant decreases in the values of AFP, which is a cancer parameter, 1 hour after the exercise. This result may be valuable in future physiotherapy studies on the relationship between exercise and cancer. PMID:27134362

  5. Luteal phase support in intrauterine insemination cycles: a prospective randomized study of 300 mg versus 600 mg intravaginal progesterone tablet.

    PubMed

    Biberoglu, Ebru H; Tanrıkulu, Filiz; Erdem, Mehmet; Erdem, Ahmet; Biberoglu, Kutay Omer

    2016-01-01

    Vaginal progesterone (P) has been suggested to be used for luteal phase support (LPS) in controlled ovarian stimulation (COH)-intrauterine insemination (IUI) cycles, however, no concensus exists about the best P dose. Therefore, considering the fecundability rate as the primary end point, our main objective was to find the optimal dose of P in COH-IUI cycles, comparing the two groups of women, each of which comprised of 100 women either on 300 mg or 600 mg of intravaginal P tablets, in a prospective randomized study design. The mean age of the women, duration of infertility, basal and day of hCG injection hormone levels in the female and sperm parameters were similar in the two study groups. Also, duration and dose of gonadotropin given, number of follicles, endometrial thickness, the total, ongoing and multiple pregnancy rates were comparable in both groups. We, therefore, claim that 300 mg of intravaginal micronized P should be the maximum dose of LPS in IUI cycles. PMID:26291817

  6. LRGS: Linear Regression by Gibbs Sampling

    NASA Astrophysics Data System (ADS)

    Mantz, Adam B.

    2016-02-01

    LRGS (Linear Regression by Gibbs Sampling) implements a Gibbs sampler to solve the problem of multivariate linear regression with uncertainties in all measured quantities and intrinsic scatter. LRGS extends an algorithm by Kelly (2007) that used Gibbs sampling for performing linear regression in fairly general cases in two ways: generalizing the procedure for multiple response variables, and modeling the prior distribution of covariates using a Dirichlet process.

  7. Quantile regression applied to spectral distance decay

    USGS Publications Warehouse

    Rocchini, D.; Cade, B.S.

    2008-01-01

    Remotely sensed imagery has long been recognized as a powerful support for characterizing and estimating biodiversity. Spectral distance among sites has proven to be a powerful approach for detecting species composition variability. Regression analysis of species similarity versus spectral distance allows us to quantitatively estimate the amount of turnover in species composition with respect to spectral and ecological variability. In classical regression analysis, the residual sum of squares is minimized for the mean of the dependent variable distribution. However, many ecological data sets are characterized by a high number of zeroes that add noise to the regression model. Quantile regressions can be used to evaluate trend in the upper quantiles rather than a mean trend across the whole distribution of the dependent variable. In this letter, we used ordinary least squares (OLS) and quantile regressions to estimate the decay of species similarity versus spectral distance. The achieved decay rates were statistically nonzero (p < 0.01), considering both OLS and quantile regressions. Nonetheless, the OLS regression estimate of the mean decay rate was only half the decay rate indicated by the upper quantiles. Moreover, the intercept value, representing the similarity reached when the spectral distance approaches zero, was very low compared with the intercepts of the upper quantiles, which detected high species similarity when habitats are more similar. In this letter, we demonstrated the power of using quantile regressions applied to spectral distance decay to reveal species diversity patterns otherwise lost or underestimated by OLS regression. ?? 2008 IEEE.

  8. Regression Calibration with Heteroscedastic Error Variance

    PubMed Central

    Spiegelman, Donna; Logan, Roger; Grove, Douglas

    2011-01-01

    The problem of covariate measurement error with heteroscedastic measurement error variance is considered. Standard regression calibration assumes that the measurement error has a homoscedastic measurement error variance. An estimator is proposed to correct regression coefficients for covariate measurement error with heteroscedastic variance. Point and interval estimates are derived. Validation data containing the gold standard must be available. This estimator is a closed-form correction of the uncorrected primary regression coefficients, which may be of logistic or Cox proportional hazards model form, and is closely related to the version of regression calibration developed by Rosner et al. (1990). The primary regression model can include multiple covariates measured without error. The use of these estimators is illustrated in two data sets, one taken from occupational epidemiology (the ACE study) and one taken from nutritional epidemiology (the Nurses’ Health Study). In both cases, although there was evidence of moderate heteroscedasticity, there was little difference in estimation or inference using this new procedure compared to standard regression calibration. It is shown theoretically that unless the relative risk is large or measurement error severe, standard regression calibration approximations will typically be adequate, even with moderate heteroscedasticity in the measurement error model variance. In a detailed simulation study, standard regression calibration performed either as well as or better than the new estimator. When the disease is rare and the errors normally distributed, or when measurement error is moderate, standard regression calibration remains the method of choice. PMID:22848187

  9. Process modeling with the regression network.

    PubMed

    van der Walt, T; Barnard, E; van Deventer, J

    1995-01-01

    A new connectionist network topology called the regression network is proposed. The structural and underlying mathematical features of the regression network are investigated. Emphasis is placed on the intricacies of the optimization process for the regression network and some measures to alleviate these difficulties of optimization are proposed and investigated. The ability of the regression network algorithm to perform either nonparametric or parametric optimization, as well as a combination of both, is also highlighted. It is further shown how the regression network can be used to model systems which are poorly understood on the basis of sparse data. A semi-empirical regression network model is developed for a metallurgical processing operation (a hydrocyclone classifier) by building mechanistic knowledge into the connectionist structure of the regression network model. Poorly understood aspects of the process are provided for by use of nonparametric regions within the structure of the semi-empirical connectionist model. The performance of the regression network model is compared to the corresponding generalization performance results obtained by some other nonparametric regression techniques.

  10. Hybrid fuzzy regression with trapezoidal fuzzy data

    NASA Astrophysics Data System (ADS)

    Razzaghnia, T.; Danesh, S.; Maleki, A.

    2011-12-01

    In this regard, this research deals with a method for hybrid fuzzy least-squares regression. The extension of symmetric triangular fuzzy coefficients to asymmetric trapezoidal fuzzy coefficients is considered as an effective measure for removing unnecessary fuzziness of the linear fuzzy model. First, trapezoidal fuzzy variable is applied to derive a bivariate regression model. In the following, normal equations are formulated to solve the four parts of hybrid regression coefficients. Also the model is extended to multiple regression analysis. Eventually, method is compared with Y-H.O. chang's model.

  11. [From clinical judgment to linear regression model.

    PubMed

    Palacios-Cruz, Lino; Pérez, Marcela; Rivas-Ruiz, Rodolfo; Talavera, Juan O

    2013-01-01

    When we think about mathematical models, such as linear regression model, we think that these terms are only used by those engaged in research, a notion that is far from the truth. Legendre described the first mathematical model in 1805, and Galton introduced the formal term in 1886. Linear regression is one of the most commonly used regression models in clinical practice. It is useful to predict or show the relationship between two or more variables as long as the dependent variable is quantitative and has normal distribution. Stated in another way, the regression is used to predict a measure based on the knowledge of at least one other variable. Linear regression has as it's first objective to determine the slope or inclination of the regression line: Y = a + bx, where "a" is the intercept or regression constant and it is equivalent to "Y" value when "X" equals 0 and "b" (also called slope) indicates the increase or decrease that occurs when the variable "x" increases or decreases in one unit. In the regression line, "b" is called regression coefficient. The coefficient of determination (R(2)) indicates the importance of independent variables in the outcome.

  12. Geodesic least squares regression on information manifolds

    SciTech Connect

    Verdoolaege, Geert

    2014-12-05

    We present a novel regression method targeted at situations with significant uncertainty on both the dependent and independent variables or with non-Gaussian distribution models. Unlike the classic regression model, the conditional distribution of the response variable suggested by the data need not be the same as the modeled distribution. Instead they are matched by minimizing the Rao geodesic distance between them. This yields a more flexible regression method that is less constrained by the assumptions imposed through the regression model. As an example, we demonstrate the improved resistance of our method against some flawed model assumptions and we apply this to scaling laws in magnetic confinement fusion.

  13. Normalization Ridge Regression in Practice I: Comparisons Between Ordinary Least Squares, Ridge Regression and Normalization Ridge Regression.

    ERIC Educational Resources Information Center

    Bulcock, J. W.

    The problem of model estimation when the data are collinear was examined. Though the ridge regression (RR) outperforms ordinary least squares (OLS) regression in the presence of acute multicollinearity, it is not a problem free technique for reducing the variance of the estimates. It is a stochastic procedure when it should be nonstochastic and it…

  14. Mulberry leaf aqueous fractions inhibit TNF-alpha-induced nuclear factor kappaB (NF-kappaB) activation and lectin-like oxidized LDL receptor-1 (LOX-1) expression in vascular endothelial cells.

    PubMed

    Shibata, Yusuke; Kume, Noriaki; Arai, Hidenori; Hayashida, Kazutaka; Inui-Hayashida, Atsuko; Minami, Manabu; Mukai, Eri; Toyohara, Masako; Harauma, Akiko; Murayama, Toshinori; Kita, Toru; Hara, Saburo; Kamei, Kaeko; Yokode, Masayuki

    2007-07-01

    Mulberry (Morus Alba L., family Moraceae) leaf extracts have various biological effects including inhibition of oxidative modification of low-density lipoprotein (LDL), which is the major cause of atherosclerosis. Endothelial dysfunction elicited by oxidized LDL (Ox-LDL) has been implicated in atherogenesis. Lectin-like Ox-LDL receptor-1 (LOX-1), a cell-surface receptor for atherogenic Ox-LDL, appears to mediate Ox-LDL-induced inflammation, which may be crucial in atherogenesis. Previous studies revealed that expression of LOX-1 is highly inducible by proinflammatory stimuli, including tumor necrosis factor-alpha (TNF-alpha), lipopolysaccharide (LPS), and transforming growth factor-beta (TGF-beta). Therefore, we examined whether mulberry leaf aqueous fractions inhibit LOX-1 expression induced by proinflammatory stimuli. Pretreatment of cultured bovine aortic endothelial cells (BAECs) with mulberry leaf aqueous fractions inhibited TNF-alpha- and LPS-induced expression of LOX-1 at both protein and mRNA levels in a time- and concentration-dependent manner. In contrast, mulberry leaf aqueous fractions did not affect TGF-beta-induced LOX-1 expression. Furthermore, mulberry leaf aqueous fractions inhibited TNF-alpha-induced activation of nuclear factor-kappaB (NF-kappaB) and phosphorylation of inhibitory factor of NF-kappaB-alpha (IkappaB-alpha) in a time- and concentration-dependent fashion. Thus, mulberry leaf aqueous fractions suppress TNF-alpha- and LPS-induced LOX-1 gene expression, by inhibiting NF-kappaB activation.

  15. TGF-beta1 enhances SDF-1alpha-induced chemotaxis and homing of naive T cells by up-regulating CXCR4 expression and downstream cytoskeletal effector molecules.

    PubMed

    Franitza, Susanne; Kollet, Orit; Brill, Alexander; Vaday, Gayle G; Petit, Isabelle; Lapidot, Tsvee; Alon, Ronen; Lider, Ofer

    2002-01-01

    The migration of immunocytes within the extracellular matrix (ECM) is influenced by the activation state of the incoming cell and its responses to the presence of chemokines and cytokines. We studied the regulatory role of TGF-beta1 on T cell homing to secondary lymphatic organs, such as the spleen, and chemotaxis within an ECM-like environment in using an ECM-like 3-dimensional gel system designed to follow the migration of individual leukocytes along chemokine gradients in real time. The numbers of migrating naive, but not memory T cells toward SDF-1alpha markedly increased after pre-incubating the cells with TGF-beta1 (0.25 ng/ml) for 24 h. The mechanisms underlying TGFbeta1-modulated migration involve the up-regulation of the expression of the SDF-1alpha receptor CXCR4, the enhancement of the SDF-1alpha-induced actin polymerization, and increased phosphorylation of Pyk2, a focal adhesion kinase involved in integrin-mediated lymphocyte migration, adhesion and interactions with ECM. Interestingly, priming of naive human T cells with TGF-beta1 increased homing of these cells to the spleen of NOD/SCID mice in a CXCR4-dependent manner. We propose that the effect of TGF-beta1 on the chemotaxis of naive T cells may be important in the locomotion of naive T cells toward SDF-1alpha-rich niches. PMID:11754360

  16. Inhibition of GSK3 differentially modulates NF-{kappa}B, CREB, AP-1 and {beta}-catenin signaling in hepatocytes, but fails to promote TNF-{alpha}-induced apoptosis

    SciTech Connect

    Goetschel, Frank; Kern, Claudia; Lang, Simona; Sparna, Titus; Markmann, Cordula; Schwager, Joseph; McNelly, Sabine; Weizsaecker, Fritz von; Laufer, Stefan; Hecht, Andreas Merfort, Irmgard

    2008-04-01

    Glycogen synthase kinase-3 (GSK-3) is known to modulate cell survival and apoptosis through multiple intracellular signaling pathways. However, its hepatoprotective function and its role in activation of NF-{kappa}B and anti-apoptotic factors are poorly understood and remain controversial. Here we investigated whether inhibition of GSK-3 could induce apoptosis in the presence of TNF-{alpha} in primary mouse hepatocytes. We show that pharmacological inhibition of GSK-3 in primary mouse hepatocytes does not lead to TNF-{alpha}-induced apoptosis despite reduced NF-{kappa}B activity. Enhanced stability of I{kappa}B-{alpha} appears to be responsible for lower levels of nuclear NF-{kappa}B and hence reduced transactivation. Additionally, inhibition of GSK-3 was accompanied by marked upregulation of {beta}-catenin, AP-1, and CREB transcription factors. Stimulation of canonical Wnt signaling and CREB activity led to elevated levels of anti-apoptotic factors. Hence, survival of primary mouse hepatocytes may be caused by the activation and/or upregulation of other key regulators of liver homeostasis and regeneration. These signaling molecules may compensate for the compromised anti-apoptotic function of NF-{kappa}B and allow survival of hepatocytes in the presence of TNF-{alpha} and GSK-3 inhibition.

  17. Formation and regression of the corpus luteum of the American alligator

    USGS Publications Warehouse

    Guillette, L.J.; Woodward, A.R.; You-Xiang, Q.; Cox, M.C.; Matter, J.H.; Gross, T.S.

    1995-01-01

    Luteal morphology of the American alligator is unique when compared to other reptiles but is similar to that of its phylogenetic relatives, the birds. The theca is extensively hypertrophied, but the granulosa never fills the cavity formed following the ovulation of the ovum. The formation of the corpus luteum (CL) is correlated with elevated plasma progesterone concentrations, which decline dramatically after oviposition with the onset of luteolysis. Unlike those of most other reptiles, the central luteal cell mass is composed of two cell types; one presumably is derived from the granulosa, whereas the other is from the theca interna. Both cell types are present throughout gravidity but only one cell type is seen during mid to late luteolysis. A significant decline in luteal volume occurs following oviposition and continues throughout the post-oviposition period. The fastest decline in luteal volume occurs in the month immediately after oviposition; this rate then slows. Luteolysis appears to continue for a year or more following oviposition, as distinct structures of luteal origin can still be identified in animals 9 months after oviposition. The size of persistent CL can be used to determine whether a given female oviposited during the previous nesting season. Females with CL having volumes greater than 0.2 cm2 or CL diameters greater than 0.4 cm were active the previous season. 

  18. Impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in Murrah buffalo (Bubalus bubalis).

    PubMed

    Pandey, A K; Dhaliwal, G S; Ghuman, S P S; Agarwal, S K

    2015-11-01

    The present study aimed to establish the impact of buserelin acetate or hCG administration on day 5 post-ovulation on subsequent luteal profile and conception rate in buffalo. The buffalo (n=45) were subjected to an estrous synchronization protocol (synthetic analog of PGF2α administered, through intramuscular route, 11 days apart), followed by artificial insemination (AI) during mid to late estrus. On day 5 post-ovulation, buffalo were administered (i.m.) normal saline (Control, n=14), buserelin acetate (20μg, d5-BA, n=14) or human chorionic gonadotropin (3000IU, d5-hCG, n=17). Ovarian ultrasonography was conducted on the day of induced estrus and on days 0, 5, 12, 16 and 21 post-ovulation to assess preovulatory follicle or corpus luteum (CL) diameter. Also, on these days, jugular vein blood sampling was conducted for the estimation of plasma progesterone. First service conception rate was greater (χ(2)=5.18, P>0.05) in d5-BA and d5-hCG groups (71.4% and 47.1%, respectively) as compared to control (28.6%). Both treatment groups had a greater (P<0.05) CL diameter and plasma progesterone during the post-treatment period in comparison to that control treatment group. Treatment-induced accessory CL formation was observed in 92.9% and 76.5% buffalo of d5-BA and d5-hCG groups, respectively. In conclusion, buserelin acetate and hCG administration on day 5 post-ovulation leads to accessory CL formation that may have a role in enhancing conception rate.

  19. Is It Possible to Prevent Ovarian Hyperstimulation Syndrome by Gonadotropin-Releasing Hormone Agonist Triggering and Modified Luteal Support in Patients With Polycystic Ovarian Morphology?

    PubMed Central

    Gurbuz, Ali Sami; Deveer, Ruya; Kucuk, Mert; Ozcimen, Necati; Incesu, Dilek; Koseoglu, Sezen

    2016-01-01

    Background Gonadotropin-releasing hormone (GnRH) agonist triggering plus 1,500 IU human chorionic gonadotropin (hCG) supplementation protocol was previously claimed effective in reducing the ovarian hyperstimulation syndrome (OHSS) incidence in high responders. Methods This retrospective study included women with polycystic ovarian (PCO) morphology who were at high risk of OHSS and were given the GnRH agonist trigger plus hCG luteal support protocol in a single center. Results The mean peak estradiol level was 5,336 ± 2,341 (1,187 - 19,746) pg/mL. The mean number of follicles > 12 mm on the day of trigger was 22 ± 7 (9 - 51). A total of 88 cycles were undertaken. Sixty-three (71.5%) women underwent fresh embryo transfer. Fresh embryo transfer was canceled in 21 (23.8%) and embryo transfer was canceled in four (4.5%) women. The overall clinical pregnancy rate was 46.4% per started cycle. A total of 12 (13.6%) patients developed OHSS. “Freeze-all” policy did not attenuate OHSS in four patients, and three of these patients developed OHSS despite 1,500 IU hCG was not administered. Conclusion We conclude that OHSS may still occur with the use of a GnRH agonist trigger combined with low-dose hCG supplementation protocol in women with polycystic ovary syndrome (PCOS) or PCO morphology. Furthermore, we also conclude that “freeze-all” policy also will not completely eliminate OHSS development in high-risk women. PMID:27081426

  20. Activity of platelet-activating factor acetylhydrolase in the mouse uterus during the estrous cycle, throughout the preimplantation phase of pregnancy, and throughout the luteal phase of pseudopregnancy.

    PubMed

    O'Neill, C

    1995-05-01

    Platelet-activating factor (PAF) is a potent autacoid produced by the embryo and the endometrium during early pregnancy. Its actions in vivo are dependent upon its half-life, which in turn is largely governed by its metabolism. PAF:acetylhydrolase is a major metabolic enzyme for PAF and is widespread in body tissues and fluids. This study was an examination of the activity of this enzyme in the uterus (uterine luminal fluids and endometrial scrapings) of mice in the periovulatory period, throughout the preimplantation phase of pregnancy, and throughout the luteal phase of pseudopregnancy. PAF:acetylhydrolase activity was found in uterine washings and endometrial tissue; it was dependent upon incubation time and protein concentration and was destroyed by boiling. The activity was not affected by cations (Mg2+ and Ca2+) and was not inhibited by bromophenacyl bromide, a phospholipase A2 inhibitor. The specific and total activity changed dramatically throughout the reproductive cycle. Total tissue activity did not change significantly during the follicular phase. On the day after ovulation, tissue activity was lower in naturally mated mice and was maintained at this level until Day 4; there was no difference in this value between pregnant and pseudopregnant animals. On days 5 and 6 of pseudopregnancy the total tissue activity increased, reaching a peak on Day 6 of 4609 pmol acetate released.min-1, approximately 780% higher than the value obtained on Day 4. Activity then decreased so that by Day 8 it was not different from preovulatory levels. For uterine luminal fluids, total activity significantly decreased during the follicular phase. This continued throughout the preimplatation phase with minimum activity being reached on Days 3 and 4 (7.68 pmol acetate.min-1 on Day 4 pseudopregnancy).(ABSTRACT TRUNCATED AT 250 WORDS)

  1. Lack of in vitro effect of aglepristone on IFN-γ and IL-4 production by resting and mitogen-activated T cells of luteal bitches

    PubMed Central

    2013-01-01

    Background Aglepristone (RU534) is an antiprogestin used for pregnancy termination, parturition induction and conservative pyometra treatment in bitches. Its molecular structure is similar to mifepristone, an antiprogestin used in human medicine. Mifepristone has been shown to suppress proliferation and cytokine production by T cells, whereas the effect of aglepristone on T cell function remains elusive. The purpose of this project was to investigate the in vitro influence of RU534 on IFN-γ and IL-4 synthesis by peripheral blood T cells isolated from healthy bitches (N = 16) in luteal phase. The peripheral blood mononuclear cells (PBMCs) were incubated with three different dosages of aglepristone, or dimethyl sulfoxide (DMSO), with or without mitogen. The production of cytokines by resting or mitogen-activated T cells was determined by intercellular staining and flow cytometry analysis or ELISA assay, respectively. Results Our results showed no statistically significant differences in the percentage of IFN-γ and IL-4-synthesizing CD4+ or CD8+ resting T cells between untreated and aglepristone-treated cells at 24 and 48 hours post treatment. Moreover, mitogen-activated PBMCs treated with RU534 displayed similar concentration of IFN-γ and IL-4 in culture supernatants to those observed in mitogen-activated DMSO-treated PBMCs. Presented results indicate that administration of aglepristone for 48 hours has no influence on IFN-γ and IL-4 synthesis by resting and mitogen-activated T cells isolated from diestral bitches. Conclusions We conclude that antiprogestins may differentially affect T cell function depending on the animal species in which they are applied. PMID:24284004

  2. The interaction between selenium status, sex hormones, and thyroid metabolism in adolescent girls in the luteal phase of their menstrual cycle.

    PubMed

    Zagrodzki, Paweł; Ratajczak, Ryszard; Wietecha-Posłuszny, Renata

    2007-01-01

    The objective of the present work was to study all physiological relationships among selenium status (SeS), sex hormones secretion (SH), and thyroid metabolism (ThM) in healthy adolescent girls, at one time. Forty-four girls aged 13.4-16.6 years (mean age, 14.5 +/- 0.5 years) entered the statistical model. Parameters reflecting SeS: plasma selenium concentration (Se) and plasma glutathione peroxidase activity (GPX3); SH: serum estradiol (E2) and progesterone (P4); age of menarche (AoM); and ThM: thyroid stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), antithyroid peroxidase antibodies (anti-TPO) in serum, and thyroid volume (ThV), were determined, and the interactions between them were evaluated by means of the partial least squares method (PLS). PLS method was, for the first time, successfully applied to the problem of selenium and hormone interactions and revealed that selenium status and female reproductive system are interrelated and affect thyroid physiology in adolescent girls in the luteal phase. The strongest associations were revealed for the pairs of parameters, Se and fT4/fT3, Se and P4, the modest ones for the pairs, Se and ThV, P4 and fT4/fT3, Se and AoM, and P4 and AoM. There was no correlation between E2, GPX3, and TSH, and any other considered parameter. Se and P4 had the greatest influence on ThM parameters.

  3. The effect of treatment with flunixin meglumine at different times relative to hCG administration on ovulation failure and luteal function in mares.

    PubMed

    Cuervo-Arango, J

    2011-08-01

    Flunixin meglumine (FM), a prostaglandin synthetase inhibitor, causes ovulatory failure in the mare. However, the effect of the FM treatment relative to the time of hCG administration on the ovulation failure has not been determined nor has its effect on the luteal function of treated mares. Estrous mares with a follicle ≥32 mm (range of 32-38 mm) were treated with 1.7 mg/kg b.w. of FM iv at zero, 12, 24 and 36 h (n=6), at 24 and 36 h (n=6), at 28 and 36 h (n=6), at 24h (n=6) or at 30 h (n=6) after treatment with 1500 IU hCG. One group received no FM (control, n=6). Progesterone concentrations were determined using RIA. Mares treated with FM 0-36 h and 24-36 h had higher (P<0.05) incidence of ovulatory failure (83 and 80%, respectively) than mares treated twice at 28 and 36 h, or once at 24 or at 30 h after hCG (16.7, 0 and 0%, respectively). The anovulatory follicles of FM treated mares luteinized and produced progesterone (>2 ng/ml). The progesterone concentration was lower in mares treated with FM at zero to 36 h and at 24-36 h after hCG than in the other groups. In conclusion, the FM administration was effective in blocking ovulation only when the treatment began ≤24 h after hCG and was continued every 12 h until ≥36 h. In addition, the FM-induced anovulatory follicles underwent luteinization of follicular cells with active production of progesterone.

  4. Suppression Situations in Multiple Linear Regression

    ERIC Educational Resources Information Center

    Shieh, Gwowen

    2006-01-01

    This article proposes alternative expressions for the two most prevailing definitions of suppression without resorting to the standardized regression modeling. The formulation provides a simple basis for the examination of their relationship. For the two-predictor regression, the author demonstrates that the previous results in the literature are…

  5. Deriving the Regression Equation without Using Calculus

    ERIC Educational Resources Information Center

    Gordon, Sheldon P.; Gordon, Florence S.

    2004-01-01

    Probably the one "new" mathematical topic that is most responsible for modernizing courses in college algebra and precalculus over the last few years is the idea of fitting a function to a set of data in the sense of a least squares fit. Whether it be simple linear regression or nonlinear regression, this topic opens the door to applying the…

  6. A Practical Guide to Regression Discontinuity

    ERIC Educational Resources Information Center

    Jacob, Robin; Zhu, Pei; Somers, Marie-Andrée; Bloom, Howard

    2012-01-01

    Regression discontinuity (RD) analysis is a rigorous nonexperimental approach that can be used to estimate program impacts in situations in which candidates are selected for treatment based on whether their value for a numeric rating exceeds a designated threshold or cut-point. Over the last two decades, the regression discontinuity approach has…

  7. Dealing with Outliers: Robust, Resistant Regression

    ERIC Educational Resources Information Center

    Glasser, Leslie

    2007-01-01

    Least-squares linear regression is the best of statistics and it is the worst of statistics. The reasons for this paradoxical claim, arising from possible inapplicability of the method and the excessive influence of "outliers", are discussed and substitute regression methods based on median selection, which is both robust and resistant, are…

  8. Cross-Validation, Shrinkage, and Multiple Regression.

    ERIC Educational Resources Information Center

    Hynes, Kevin

    One aspect of multiple regression--the shrinkage of the multiple correlation coefficient on cross-validation is reviewed. The paper consists of four sections. In section one, the distinction between a fixed and a random multiple regression model is made explicit. In section two, the cross-validation paradigm and an explanation for the occurrence…

  9. Application and Interpretation of Hierarchical Multiple Regression.

    PubMed

    Jeong, Younhee; Jung, Mi Jung

    2016-01-01

    The authors reported the association between motivation and self-management behavior of individuals with chronic low back pain after adjusting control variables using hierarchical multiple regression (). This article describes details of the hierarchical regression applying the actual data used in the article by , including how to test assumptions, run the statistical tests, and report the results. PMID:27648796

  10. Regression Analysis: Legal Applications in Institutional Research

    ERIC Educational Resources Information Center

    Frizell, Julie A.; Shippen, Benjamin S., Jr.; Luna, Andrew L.

    2008-01-01

    This article reviews multiple regression analysis, describes how its results should be interpreted, and instructs institutional researchers on how to conduct such analyses using an example focused on faculty pay equity between men and women. The use of multiple regression analysis will be presented as a method with which to compare salaries of…

  11. A Simulation Investigation of Principal Component Regression.

    ERIC Educational Resources Information Center

    Allen, David E.

    Regression analysis is one of the more common analytic tools used by researchers. However, multicollinearity between the predictor variables can cause problems in using the results of regression analyses. Problems associated with multicollinearity include entanglement of relative influences of variables due to reduced precision of estimation,…

  12. Incremental Net Effects in Multiple Regression

    ERIC Educational Resources Information Center

    Lipovetsky, Stan; Conklin, Michael

    2005-01-01

    A regular problem in regression analysis is estimating the comparative importance of the predictors in the model. This work considers the 'net effects', or shares of the predictors in the coefficient of the multiple determination, which is a widely used characteristic of the quality of a regression model. Estimation of the net effects can be a…

  13. Illustration of Regression towards the Means

    ERIC Educational Resources Information Center

    Govindaraju, K.; Haslett, S. J.

    2008-01-01

    This article presents a procedure for generating a sequence of data sets which will yield exactly the same fitted simple linear regression equation y = a + bx. Unless rescaled, the generated data sets will have progressively smaller variability for the two variables, and the associated response and covariate will "regress" towards their…

  14. Regression Analysis and the Sociological Imagination

    ERIC Educational Resources Information Center

    De Maio, Fernando

    2014-01-01

    Regression analysis is an important aspect of most introductory statistics courses in sociology but is often presented in contexts divorced from the central concerns that bring students into the discipline. Consequently, we present five lesson ideas that emerge from a regression analysis of income inequality and mortality in the USA and Canada.

  15. Three-Dimensional Modeling in Linear Regression.

    ERIC Educational Resources Information Center

    Herman, James D.

    Linear regression examines the relationship between one or more independent (predictor) variables and a dependent variable. By using a particular formula, regression determines the weights needed to minimize the error term for a given set of predictors. With one predictor variable, the relationship between the predictor and the dependent variable…

  16. Nodule Regression in Adults With Nodular Gastritis

    PubMed Central

    Kim, Ji Wan; Lee, Sun-Young; Kim, Jeong Hwan; Sung, In-Kyung; Park, Hyung Seok; Shim, Chan-Sup; Han, Hye Seung

    2015-01-01

    Background Nodular gastritis (NG) is associated with the presence of Helicobacter pylori infection, but there are controversies on nodule regression in adults. The aim of this study was to analyze the factors that are related to the nodule regression in adults diagnosed as NG. Methods Adult population who were diagnosed as NG with H. pylori infection during esophagogastroduodenoscopy (EGD) at our center were included. Changes in the size and location of the nodules, status of H. pylori infection, upper gastrointestinal (UGI) symptom, EGD and pathology findings were analyzed between the initial and follow-up tests. Results Of the 117 NG patients, 66.7% (12/18) of the eradicated NG patients showed nodule regression after H. pylori eradication, whereas 9.9% (9/99) of the non-eradicated NG patients showed spontaneous nodule regression without H. pylori eradication (P < 0.001). Nodule regression was more frequent in NG patients with antral nodule location (P = 0.010), small-sized nodules (P = 0.029), H. pylori eradication (P < 0.001), UGI symptom (P = 0.007), and a long-term follow-up period (P = 0.030). On the logistic regression analysis, nodule regression was inversely correlated with the persistent H. pylori infection on the follow-up test (odds ratio (OR): 0.020, 95% confidence interval (CI): 0.003 - 0.137, P < 0.001) and short-term follow-up period < 30.5 months (OR: 0.140, 95% CI: 0.028 - 0.700, P = 0.017). Conclusions In adults with NG, H. pylori eradication is the most significant factor associated with nodule regression. Long-term follow-up period is also correlated with nodule regression, but is less significant than H. pylori eradication. Our findings suggest that H. pylori eradication should be considered to promote nodule regression in NG patients with H. pylori infection.

  17. Regression modeling of ground-water flow

    USGS Publications Warehouse

    Cooley, R.L.; Naff, R.L.

    1985-01-01

    Nonlinear multiple regression methods are developed to model and analyze groundwater flow systems. Complete descriptions of regression methodology as applied to groundwater flow models allow scientists and engineers engaged in flow modeling to apply the methods to a wide range of problems. Organization of the text proceeds from an introduction that discusses the general topic of groundwater flow modeling, to a review of basic statistics necessary to properly apply regression techniques, and then to the main topic: exposition and use of linear and nonlinear regression to model groundwater flow. Statistical procedures are given to analyze and use the regression models. A number of exercises and answers are included to exercise the student on nearly all the methods that are presented for modeling and statistical analysis. Three computer programs implement the more complex methods. These three are a general two-dimensional, steady-state regression model for flow in an anisotropic, heterogeneous porous medium, a program to calculate a measure of model nonlinearity with respect to the regression parameters, and a program to analyze model errors in computed dependent variables such as hydraulic head. (USGS)

  18. A comparison of regression and regression-kriging for soil characterization using remote sensing imagery

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In precision agriculture regression has been used widely to quality the relationship between soil attributes and other environmental variables. However, spatial correlation existing in soil samples usually makes the regression model suboptimal. In this study, a regression-kriging method was attemp...

  19. Modelling of filariasis in East Java with Poisson regression and generalized Poisson regression models

    NASA Astrophysics Data System (ADS)

    Darnah

    2016-04-01

    Poisson regression has been used if the response variable is count data that based on the Poisson distribution. The Poisson distribution assumed equal dispersion. In fact, a situation where count data are over dispersion or under dispersion so that Poisson regression inappropriate because it may underestimate the standard errors and overstate the significance of the regression parameters, and consequently, giving misleading inference about the regression parameters. This paper suggests the generalized Poisson regression model to handling over dispersion and under dispersion on the Poisson regression model. The Poisson regression model and generalized Poisson regression model will be applied the number of filariasis cases in East Java. Based regression Poisson model the factors influence of filariasis are the percentage of families who don't behave clean and healthy living and the percentage of families who don't have a healthy house. The Poisson regression model occurs over dispersion so that we using generalized Poisson regression. The best generalized Poisson regression model showing the factor influence of filariasis is percentage of families who don't have healthy house. Interpretation of result the model is each additional 1 percentage of families who don't have healthy house will add 1 people filariasis patient.

  20. Regression of altitude-produced cardiac hypertrophy.

    NASA Technical Reports Server (NTRS)

    Sizemore, D. A.; Mcintyre, T. W.; Van Liere, E. J.; Wilson , M. F.

    1973-01-01

    The rate of regression of cardiac hypertrophy with time has been determined in adult male albino rats. The hypertrophy was induced by intermittent exposure to simulated high altitude. The percentage hypertrophy was much greater (46%) in the right ventricle than in the left (16%). The regression could be adequately fitted to a single exponential function with a half-time of 6.73 plus or minus 0.71 days (90% CI). There was no significant difference in the rates of regression for the two ventricles.

  1. Tumour necrosis factor-alpha-induced glucose-stimulated insulin secretion inhibition in INS-1 cells is ascribed to a reduction of the glucose-stimulated Ca2+ influx.

    PubMed

    Kim, Hyo-Eun; Choi, Sung-E; Lee, Soo-Jin; Lee, Ji-Hyun; Lee, Youn-Jung; Kang, Sang Sun; Chun, Jaesun; Kang, Yup

    2008-09-01

    The present study was undertaken to determine how tumour necrosis factor-alpha (TNF-alpha) elicits the inhibition of glucose-stimulated insulin secretion (GSIS) in rat insulinoma cells (INS)-1 beta-cells. TNF-alpha pretreatment did not change the expression levels of insulin, PDX-1, glucose transporter 2, glucokinase, K(ATP) channels, Ca(2)(+) channels, and exocytotic molecules and, furthermore, did not reduce the glucose-stimulated ATP level. On the other hand, TNF-alpha reduced the glucose-stimulated influx of Ca(2)(+). The TNF-alpha treatment was thought to activate c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), and NF-kappaB inflammatory signals, since TNF-alpha increased phospho-JNK and phospho-p38 and reduced I kappaB levels. Inhibitors of these signaling pathways prevented the TNF-alpha-induced reduction of the Ca(2)(+) influx and GSIS. Overexpression of MEKK3, a possible mediator from the TNF-alpha receptor to the JNK/p38 and NK-kappaB signaling cascade, increased the levels of phospho-JNK, phospho-p38, and NF-kappaB, and reduced the glucose-stimulated Ca(2)(+) influx and GSIS. The reduction of the Ca(2)(+) influx and GSIS in MEKK3-overexpressing INS-1 cells was also prevented by inhibitors of JNK, p38, and NF-kappaB. These data demonstrate that TNF-alpha inhibits GSIS by reducing the glucose-stimulated Ca(2)(+) influx, possibly through the activation of JNK and p38 MAPK and NF-kappaB inflammatory signals. Thus, our findings suggest that the activation of stress and inflammatory signals can contribute to the inhibition of GSIS in the development of diabetes.

  2. REGRESSION ESTIMATES FOR TOPOLOGICAL-HYDROGRAPH INPUT.

    USGS Publications Warehouse

    Karlinger, Michael R.; Guertin, D. Phillip; Troutman, Brent M.

    1988-01-01

    Physiographic, hydrologic, and rainfall data from 18 small drainage basins in semiarid, central Wyoming were used to calibrate topological, unit-hydrograph models for celerity, the average rate of travel of a flood wave through the basin. The data set consisted of basin characteristics and hydrologic data for the 18 basins and rainfall data for 68 storms. Calibrated values of celerity and peak discharges subsequently were regressed as a function of the basin characteristics and excess rainfall volume. Predicted values obtained in this way can be used as input for estimating hydrographs in ungaged basins. The regression models included ordinary least-squares and seemingly unrelated regression. This latter regression model jointly estimated the celerity and peak discharge.

  3. TWSVR: Regression via Twin Support Vector Machine.

    PubMed

    Khemchandani, Reshma; Goyal, Keshav; Chandra, Suresh

    2016-02-01

    Taking motivation from Twin Support Vector Machine (TWSVM) formulation, Peng (2010) attempted to propose Twin Support Vector Regression (TSVR) where the regressor is obtained via solving a pair of quadratic programming problems (QPPs). In this paper we argue that TSVR formulation is not in the true spirit of TWSVM. Further, taking motivation from Bi and Bennett (2003), we propose an alternative approach to find a formulation for Twin Support Vector Regression (TWSVR) which is in the true spirit of TWSVM. We show that our proposed TWSVR can be derived from TWSVM for an appropriately constructed classification problem. To check the efficacy of our proposed TWSVR we compare its performance with TSVR and classical Support Vector Regression(SVR) on various regression datasets.

  4. TWSVR: Regression via Twin Support Vector Machine.

    PubMed

    Khemchandani, Reshma; Goyal, Keshav; Chandra, Suresh

    2016-02-01

    Taking motivation from Twin Support Vector Machine (TWSVM) formulation, Peng (2010) attempted to propose Twin Support Vector Regression (TSVR) where the regressor is obtained via solving a pair of quadratic programming problems (QPPs). In this paper we argue that TSVR formulation is not in the true spirit of TWSVM. Further, taking motivation from Bi and Bennett (2003), we propose an alternative approach to find a formulation for Twin Support Vector Regression (TWSVR) which is in the true spirit of TWSVM. We show that our proposed TWSVR can be derived from TWSVM for an appropriately constructed classification problem. To check the efficacy of our proposed TWSVR we compare its performance with TSVR and classical Support Vector Regression(SVR) on various regression datasets. PMID:26624223

  5. Some Simple Computational Formulas for Multiple Regression

    ERIC Educational Resources Information Center

    Aiken, Lewis R., Jr.

    1974-01-01

    Short-cut formulas are presented for direct computation of the beta weights, the standard errors of the beta weights, and the multiple correlation coefficient for multiple regression problems involving three independent variables and one dependent variable. (Author)

  6. The Geometry of Enhancement in Multiple Regression

    ERIC Educational Resources Information Center

    Waller, Niels G.

    2011-01-01

    In linear multiple regression, "enhancement" is said to occur when R[superscript 2] = b[prime]r greater than r[prime]r, where b is a p x 1 vector of standardized regression coefficients and r is a p x 1 vector of correlations between a criterion y and a set of standardized regressors, x. When p = 1 then b [is congruent to] r and enhancement cannot…

  7. There is No Quantum Regression Theorem

    SciTech Connect

    Ford, G.W.; OConnell, R.F.

    1996-07-01

    The Onsager regression hypothesis states that the regression of fluctuations is governed by macroscopic equations describing the approach to equilibrium. It is here asserted that this hypothesis fails in the quantum case. This is shown first by explicit calculation for the example of quantum Brownian motion of an oscillator and then in general from the fluctuation-dissipation theorem. It is asserted that the correct generalization of the Onsager hypothesis is the fluctuation-dissipation theorem. {copyright} {ital 1996 The American Physical Society.}

  8. Synthesizing regression results: a factored likelihood method.

    PubMed

    Wu, Meng-Jia; Becker, Betsy Jane

    2013-06-01

    Regression methods are widely used by researchers in many fields, yet methods for synthesizing regression results are scarce. This study proposes using a factored likelihood method, originally developed to handle missing data, to appropriately synthesize regression models involving different predictors. This method uses the correlations reported in the regression studies to calculate synthesized standardized slopes. It uses available correlations to estimate missing ones through a series of regressions, allowing us to synthesize correlations among variables as if each included study contained all the same variables. Great accuracy and stability of this method under fixed-effects models were found through Monte Carlo simulation. An example was provided to demonstrate the steps for calculating the synthesized slopes through sweep operators. By rearranging the predictors in the included regression models or omitting a relatively small number of correlations from those models, we can easily apply the factored likelihood method to many situations involving synthesis of linear models. Limitations and other possible methods for synthesizing more complicated models are discussed. Copyright © 2012 John Wiley & Sons, Ltd. PMID:26053653

  9. Post-processing through linear regression

    NASA Astrophysics Data System (ADS)

    van Schaeybroeck, B.; Vannitsem, S.

    2011-03-01

    Various post-processing techniques are compared for both deterministic and ensemble forecasts, all based on linear regression between forecast data and observations. In order to evaluate the quality of the regression methods, three criteria are proposed, related to the effective correction of forecast error, the optimal variability of the corrected forecast and multicollinearity. The regression schemes under consideration include the ordinary least-square (OLS) method, a new time-dependent Tikhonov regularization (TDTR) method, the total least-square method, a new geometric-mean regression (GM), a recently introduced error-in-variables (EVMOS) method and, finally, a "best member" OLS method. The advantages and drawbacks of each method are clarified. These techniques are applied in the context of the 63 Lorenz system, whose model version is affected by both initial condition and model errors. For short forecast lead times, the number and choice of predictors plays an important role. Contrarily to the other techniques, GM degrades when the number of predictors increases. At intermediate lead times, linear regression is unable to provide corrections to the forecast and can sometimes degrade the performance (GM and the best member OLS with noise). At long lead times the regression schemes (EVMOS, TDTR) which yield the correct variability and the largest correlation between ensemble error and spread, should be preferred.

  10. Dose-response effects of phytoestrogens on the activity and expression of 3beta-hydroxysteroid dehydrogenase and aromatase in human granulosa-luteal cells.

    PubMed

    Lacey, Michael; Bohday, Jemma; Fonseka, Shamara M R; Ullah, Amer I; Whitehead, Saffron A

    2005-08-01

    There is evidence that certain phytoestrogens can inhibit key steroidogenic enzymes although most studies have been carried out on microsomal or purified enzyme preparations, some using cell lines. This study was designed to test the hypothesis that low doses of phytoestrogens, at concentrations that would be attained through the diet, could inhibit 3beta-hydroxysteroid dehydrogenase (HSD) and/or aromatase in primary cultures of human granulosa-luteal (GL) cells and that this effect was due to a decrease in the expression of these proteins. Based on published evidence, eight compounds were selected for investigation and these included the flavones apigenin and quercetin, the isoflavones genistein, biochanin A and daidzein, the lignans, enterodiol and enterolactone, and the mycotoxin zearalenone. Human GL cells were cultured for 48 h in the presence of these phytoestrogens at concentrations ranging from 0.01 to 100 microM and after addition of fresh media the conversion of pregnenolone to progesterone or androstenedione to oestradiol over a 4h period was measured. Biochanin A was the only phytoestrogen that displayed any dose-dependent inhibition of 3beta-HSD, others showing inhibition at doses >/=10 microM. Apigenin and quercetin only inhibited aromatase/17beta-HSD at high doses as did genistein, biochanin A and daidzein. The lignans had weak inhibitory effects on aromatase/17beta-HSD, whilst zearalenone showed potent inhibition at 0.1 microM. Phytoestrogens did not exert any significant effects on protein expression of 3beta-HSD or aromatase as determined by Western blots. It is concluded that steroidogenic enzymes are inhibited by phytoestrogens in primary cultures of human GL cells but these cells are less sensitive to the effects of phytoestrogens than cell-free systems. This may be due to poor lipid solubility or cellular metabolism. We have also shown for the first time that phytoestrogens do not act by inhibiting the cellular concentration of 3beta-HSD and

  11. Alpha-induced reactions in iridium

    SciTech Connect

    Bhardwaj, M.K.; Rizvi, I.A.; Chaubey, A.K. )

    1992-05-01

    The excitation function of ({alpha},{ital xn}) reactions on {sup 191}Ir (abundance 37.3%) and on {sup 193}Ir (abundance 62.7%) has been measured for the 17--55 MeV alpha-particle bombarding energy range. The stacked foil activation technique and {gamma}-ray spectroscopy were used to determine the cross sections. The experimental data were compared with calculated values obtained by means of a geometry-dependent hybrid model. The initial exciton number {ital n}{sub 0}=4 with {ital n}=2, {ital p}=2, and {ital h}=0 gives the best agreements with the presently measured results. To calculate the excitation function theoretically a computer code was used. This set of excitation functions provides a data basis for probing the validity of combined equilibrium and preequilibrium reaction models in a considerable energy range.

  12. An empirical evaluation of spatial regression models

    NASA Astrophysics Data System (ADS)

    Gao, Xiaolu; Asami, Yasushi; Chung, Chang-Jo F.

    2006-10-01

    Conventional statistical methods are often ineffective to evaluate spatial regression models. One reason is that spatial regression models usually have more parameters or smaller sample sizes than a simple model, so their degree of freedom is reduced. Thus, it is often unlikely to evaluate them based on traditional tests. Another reason, which is theoretically associated with statistical methods, is that statistical criteria are crucially dependent on such assumptions as normality, independence, and homogeneity. This may create problems because the assumptions are open for testing. In view of these problems, this paper proposes an alternative empirical evaluation method. To illustrate the idea, a few hedonic regression models for a house and land price data set are evaluated, including a simple, ordinary linear regression model and three spatial models. Their performance as to how well the price of the house and land can be predicted is examined. With a cross-validation technique, the prices at each sample point are predicted with a model estimated with the samples excluding the one being concerned. Then, empirical criteria are established whereby the predicted prices are compared with the real, observed prices. The proposed method provides an objective guidance for the selection of a suitable model specification for a data set. Moreover, the method is seen as an alternative way to test the significance of the spatial relationships being concerned in spatial regression models.

  13. Response-adaptive regression for longitudinal data.

    PubMed

    Wu, Shuang; Müller, Hans-Georg

    2011-09-01

    We propose a response-adaptive model for functional linear regression, which is adapted to sparsely sampled longitudinal responses. Our method aims at predicting response trajectories and models the regression relationship by directly conditioning the sparse and irregular observations of the response on the predictor, which can be of scalar, vector, or functional type. This obliterates the need to model the response trajectories, a task that is challenging for sparse longitudinal data and was previously required for functional regression implementations for longitudinal data. The proposed approach turns out to be superior compared to previous functional regression approaches in terms of prediction error. It encompasses a variety of regression settings that are relevant for the functional modeling of longitudinal data in the life sciences. The improved prediction of response trajectories with the proposed response-adaptive approach is illustrated for a longitudinal study of Kiwi weight growth and by an analysis of the dynamic relationship between viral load and CD4 cell counts observed in AIDS clinical trials. PMID:21133880

  14. Mental chronometry with simple linear regression.

    PubMed

    Chen, J Y

    1997-10-01

    Typically, mental chronometry is performed by means of introducing an independent variable postulated to affect selectively some stage of a presumed multistage process. However, the effect could be a global one that spreads proportionally over all stages of the process. Currently, there is no method to test this possibility although simple linear regression might serve the purpose. In the present study, the regression approach was tested with tasks (memory scanning and mental rotation) that involved a selective effect and with a task (word superiority effect) that involved a global effect, by the dominant theories. The results indicate (1) the manipulation of the size of a memory set or of angular disparity affects the intercept of the regression function that relates the times for memory scanning with different set sizes or for mental rotation with different angular disparities and (2) the manipulation of context affects the slope of the regression function that relates the times for detecting a target character under word and nonword conditions. These ratify the regression approach as a useful method for doing mental chronometry. PMID:9347535

  15. Hierarchical regression for analyses of multiple outcomes.

    PubMed

    Richardson, David B; Hamra, Ghassan B; MacLehose, Richard F; Cole, Stephen R; Chu, Haitao

    2015-09-01

    In cohort mortality studies, there often is interest in associations between an exposure of primary interest and mortality due to a range of different causes. A standard approach to such analyses involves fitting a separate regression model for each type of outcome. However, the statistical precision of some estimated associations may be poor because of sparse data. In this paper, we describe a hierarchical regression model for estimation of parameters describing outcome-specific relative rate functions and associated credible intervals. The proposed model uses background stratification to provide flexible control for the outcome-specific associations of potential confounders, and it employs a hierarchical "shrinkage" approach to stabilize estimates of an exposure's associations with mortality due to different causes of death. The approach is illustrated in analyses of cancer mortality in 2 cohorts: a cohort of dioxin-exposed US chemical workers and a cohort of radiation-exposed Japanese atomic bomb survivors. Compared with standard regression estimates of associations, hierarchical regression yielded estimates with improved precision that tended to have less extreme values. The hierarchical regression approach also allowed the fitting of models with effect-measure modification. The proposed hierarchical approach can yield estimates of association that are more precise than conventional estimates when one wishes to estimate associations with multiple outcomes. PMID:26232395

  16. MULTILINEAR TENSOR REGRESSION FOR LONGITUDINAL RELATIONAL DATA

    PubMed Central

    Hoff, Peter D.

    2016-01-01

    A fundamental aspect of relational data, such as from a social network, is the possibility of dependence among the relations. In particular, the relations between members of one pair of nodes may have an effect on the relations between members of another pair. This article develops a type of regression model to estimate such effects in the context of longitudinal and multivariate relational data, or other data that can be represented in the form of a tensor. The model is based on a general multilinear tensor regression model, a special case of which is a tensor autoregression model in which the tensor of relations at one time point are parsimoniously regressed on relations from previous time points. This is done via a separable, or Kronecker-structured, regression parameter along with a separable covariance model. In the context of an analysis of longitudinal multivariate relational data, it is shown how the multilinear tensor regression model can represent patterns that often appear in relational and network data, such as reciprocity and transitivity. PMID:27458495

  17. Uncertainty quantification in DIC with Kriging regression

    NASA Astrophysics Data System (ADS)

    Wang, Dezhi; DiazDelaO, F. A.; Wang, Weizhuo; Lin, Xiaoshan; Patterson, Eann A.; Mottershead, John E.

    2016-03-01

    A Kriging regression model is developed as a post-processing technique for the treatment of measurement uncertainty in classical subset-based Digital Image Correlation (DIC). Regression is achieved by regularising the sample-point correlation matrix using a local, subset-based, assessment of the measurement error with assumed statistical normality and based on the Sum of Squared Differences (SSD) criterion. This leads to a Kriging-regression model in the form of a Gaussian process representing uncertainty on the Kriging estimate of the measured displacement field. The method is demonstrated using numerical and experimental examples. Kriging estimates of displacement fields are shown to be in excellent agreement with 'true' values for the numerical cases and in the experimental example uncertainty quantification is carried out using the Gaussian random process that forms part of the Kriging model. The root mean square error (RMSE) on the estimated displacements is produced and standard deviations on local strain estimates are determined.

  18. A tutorial on Bayesian Normal linear regression

    NASA Astrophysics Data System (ADS)

    Klauenberg, Katy; Wübbeler, Gerd; Mickan, Bodo; Harris, Peter; Elster, Clemens

    2015-12-01

    Regression is a common task in metrology and often applied to calibrate instruments, evaluate inter-laboratory comparisons or determine fundamental constants, for example. Yet, a regression model cannot be uniquely formulated as a measurement function, and consequently the Guide to the Expression of Uncertainty in Measurement (GUM) and its supplements are not applicable directly. Bayesian inference, however, is well suited to regression tasks, and has the advantage of accounting for additional a priori information, which typically robustifies analyses. Furthermore, it is anticipated that future revisions of the GUM shall also embrace the Bayesian view. Guidance on Bayesian inference for regression tasks is largely lacking in metrology. For linear regression models with Gaussian measurement errors this tutorial gives explicit guidance. Divided into three steps, the tutorial first illustrates how a priori knowledge, which is available from previous experiments, can be translated into prior distributions from a specific class. These prior distributions have the advantage of yielding analytical, closed form results, thus avoiding the need to apply numerical methods such as Markov Chain Monte Carlo. Secondly, formulas for the posterior results are given, explained and illustrated, and software implementations are provided. In the third step, Bayesian tools are used to assess the assumptions behind the suggested approach. These three steps (prior elicitation, posterior calculation, and robustness to prior uncertainty and model adequacy) are critical to Bayesian inference. The general guidance given here for Normal linear regression tasks is accompanied by a simple, but real-world, metrological example. The calibration of a flow device serves as a running example and illustrates the three steps. It is shown that prior knowledge from previous calibrations of the same sonic nozzle enables robust predictions even for extrapolations.

  19. MLREG, stepwise multiple linear regression program

    SciTech Connect

    Carder, J.H.

    1981-09-01

    This program is written in FORTRAN for an IBM computer and performs multiple linear regressions according to a stepwise procedure. The program transforms and combines old variables into new variables, prints input and transformed data, sums, raw sums or squares, residual sum of squares, means and standard deviations, correlation coefficients, regression results at each step, ANOVA at each step, and predicted response results at each step. This package contains an EXEC used to execute the program,sample input data and output listing, source listing, documentation, and card decks containing the EXEC sample input, and FORTRAN source.

  20. Salience Assignment for Multiple-Instance Regression

    NASA Technical Reports Server (NTRS)

    Wagstaff, Kiri L.; Lane, Terran

    2007-01-01

    We present a Multiple-Instance Learning (MIL) algorithm for determining the salience of each item in each bag with respect to the bag's real-valued label. We use an alternating-projections constrained optimization approach to simultaneously learn a regression model and estimate all salience values. We evaluate this algorithm on a significant real-world problem, crop yield modeling, and demonstrate that it provides more extensive, intuitive, and stable salience models than Primary-Instance Regression, which selects a single relevant item from each bag.

  1. Spontaneous regression of a conjunctival naevus.

    PubMed

    Haldar, Shreya; Leyland, Martin

    2016-01-01

    Conjunctival naevi are one of the most common lesions affecting the conjunctiva. While benign in the vast majority of cases, the risk of malignant transformation necessitates regular follow-up. They are well known to increase in size; however, we present the first photo-documented case of spontaneous regression of conjunctival naevus. In most cases, surgical excision is performed due to the clinician's concerns over malignancy. However, a substantial proportion of patients request excision. Highlighting the potential for regression of the lesion is important to ensure patients make an informed decision when contemplating such surgery. PMID:27581234

  2. Removing Malmquist bias from linear regressions

    NASA Technical Reports Server (NTRS)

    Verter, Frances

    1993-01-01

    Malmquist bias is present in all astronomical surveys where sources are observed above an apparent brightness threshold. Those sources which can be detected at progressively larger distances are progressively more limited to the intrinsically luminous portion of the true distribution. This bias does not distort any of the measurements, but distorts the sample composition. We have developed the first treatment to correct for Malmquist bias in linear regressions of astronomical data. A demonstration of the corrected linear regression that is computed in four steps is presented.

  3. Multicollinearity in cross-sectional regressions

    NASA Astrophysics Data System (ADS)

    Lauridsen, Jørgen; Mur, Jesùs

    2006-10-01

    The paper examines robustness of results from cross-sectional regression paying attention to the impact of multicollinearity. It is well known that the reliability of estimators (least-squares or maximum-likelihood) gets worse as the linear relationships between the regressors become more acute. We resolve the discussion in a spatial context, looking closely into the behaviour shown, under several unfavourable conditions, by the most outstanding misspecification tests when collinear variables are added to the regression. A Monte Carlo simulation is performed. The conclusions point to the fact that these statistics react in different ways to the problems posed.

  4. Spontaneous hypnotic age regression: case report.

    PubMed

    Spiegel, D; Rosenfeld, A

    1984-12-01

    Age regression--reliving the past as though it were occurring in the present, with age appropriate vocabulary, mental content, and affect--can occur with instruction in highly hypnotizable individuals, but has rarely been reported to occur spontaneously, especially as a primary symptom. The psychiatric presentation and treatment of a 16-year-old girl with spontaneous age regressions accessible and controllable with hypnosis and psychotherapy are described. Areas of overlap and divergence between this patient's symptoms and those found in patients with hysterical fugue and multiple personality syndrome are also discussed.

  5. SM22{alpha}-induced activation of p16{sup INK4a}/retinoblastoma pathway promotes cellular senescence caused by a subclinical dose of {gamma}-radiation and doxorubicin in HepG2 cells

    SciTech Connect

    Kim, Tae Rim; Lee, Hee Min; Lee, So Yong; Kim, Eun Jin; Kim, Kug Chan; Paik, Sang Gi; Cho, Eun Wie; Kim, In Gyu

    2010-09-10

    Research highlights: {yields} SM22{alpha} overexpression in HepG2 cells leads cells to a growth arrest state, and the treatment of a subclinical dose of {gamma}-radiation or doxorubicin promotes cellular senescence. {yields} SM22{alpha} overexpression elevates p16{sup INK4a} followed by pRB activation, but there are no effects on p53/p21{sup WAF1/Cip1} pathway. {yields} SM22{alpha}-induced MT-1G activates p16{sup INK4a}/pRB pathway, which promotes cellular senescence by damaging agents. -- Abstract: Smooth muscle protein 22-alpha (SM22{alpha}) is known as a transformation- and shape change-sensitive actin cross-linking protein found in smooth muscle tissue and fibroblasts; however, its functional role remains uncertain. We reported previously that SM22{alpha} overexpression confers resistance against anti-cancer drugs or radiation via induction of metallothionein (MT) isozymes in HepG2 cells. In this study, we demonstrate that SM22{alpha} overexpression leads cells to a growth arrest state and promotes cellular senescence caused by treatment with a subclinical dose of {gamma}-radiation (0.05 and 0.1 Gy) or doxorubicin (0.01 and 0.05 {mu}g/ml), compared to control cells. Senescence growth arrest is known to be controlled by p53 phosphorylation/p21{sup WAF1/Cip1} induction or p16{sup INK4a}/retinoblastoma protein (pRB) activation. SM22{alpha} overexpression in HepG2 cells elevated p16{sup INK4a} followed by pRB activation, but did not activate the p53/p21{sup WAF1/Cip1} pathway. Moreover, MT-1G, which is induced by SM22{alpha} overexpression, was involved in the activation of the p16{sup INK4a}/pRB pathway, which led to a growth arrest state and promoted cellular senescence caused by damaging agents. Our findings provide the first demonstration that SM22{alpha} modulates cellular senescence caused by damaging agents via regulation of the p16{sup INK4a}/pRB pathway in HepG2 cells and that these effects of SM22{alpha} are partially mediated by MT-1G.

  6. Logistic regression when binary predictor variables are highly correlated.

    PubMed

    Barker, L; Brown, C

    Standard logistic regression can produce estimates having large mean square error when predictor variables are multicollinear. Ridge regression and principal components regression can reduce the impact of multicollinearity in ordinary least squares regression. Generalizations of these, applicable in the logistic regression framework, are alternatives to standard logistic regression. It is shown that estimates obtained via ridge and principal components logistic regression can have smaller mean square error than estimates obtained through standard logistic regression. Recommendations for choosing among standard, ridge and principal components logistic regression are developed. Published in 2001 by John Wiley & Sons, Ltd.

  7. Bootstrap inference longitudinal semiparametric regression model

    NASA Astrophysics Data System (ADS)

    Pane, Rahmawati; Otok, Bambang Widjanarko; Zain, Ismaini; Budiantara, I. Nyoman

    2016-02-01

    Semiparametric regression contains two components, i.e. parametric and nonparametric component. Semiparametric regression model is represented by yt i=μ (x˜'ti,zt i)+εt i where μ (x˜'ti,zt i)=x˜'tiβ ˜+g (zt i) and yti is response variable. It is assumed to have a linear relationship with the predictor variables x˜'ti=(x1 i 1,x2 i 2,…,xT i r) . Random error εti, i = 1, …, n, t = 1, …, T is normally distributed with zero mean and variance σ2 and g(zti) is a nonparametric component. The results of this study showed that the PLS approach on longitudinal semiparametric regression models obtain estimators β˜^t=[X'H(λ)X]-1X'H(λ )y ˜ and g˜^λ(z )=M (λ )y ˜ . The result also show that bootstrap was valid on longitudinal semiparametric regression model with g^λ(b )(z ) as nonparametric component estimator.

  8. Assessing risk factors for periodontitis using regression

    NASA Astrophysics Data System (ADS)

    Lobo Pereira, J. A.; Ferreira, Maria Cristina; Oliveira, Teresa

    2013-10-01

    Multivariate statistical analysis is indispensable to assess the associations and interactions between different factors and the risk of periodontitis. Among others, regression analysis is a statistical technique widely used in healthcare to investigate and model the relationship between variables. In our work we study the impact of socio-demographic, medical and behavioral factors on periodontal health. Using regression, linear and logistic models, we can assess the relevance, as risk factors for periodontitis disease, of the following independent variables (IVs): Age, Gender, Diabetic Status, Education, Smoking status and Plaque Index. The multiple linear regression analysis model was built to evaluate the influence of IVs on mean Attachment Loss (AL). Thus, the regression coefficients along with respective p-values will be obtained as well as the respective p-values from the significance tests. The classification of a case (individual) adopted in the logistic model was the extent of the destruction of periodontal tissues defined by an Attachment Loss greater than or equal to 4 mm in 25% (AL≥4mm/≥25%) of sites surveyed. The association measures include the Odds Ratios together with the correspondent 95% confidence intervals.

  9. Nodular fasciitis with degeneration and regression.

    PubMed

    Yanagisawa, Akihiro; Okada, Hideki

    2008-07-01

    Nodular fasciitis is a benign reactive proliferation that is frequently misdiagnosed as a sarcoma. This article describes a case of nodular fasciitis of 6-month duration located in the cheek, which degenerated and spontaneously regressed after biopsy. The nodule was fixed to the zygoma but was free from the overlying skin. The mass was 3.0 cm in diameter and demonstrated high signal intensity on T2-weighted magnetic resonance imaging. A small part of the lesion was biopsied. Pathological and immunohistochemical examinations identified the nodule as nodular fasciitis with myxoid histology. One month after the biopsy, the mass showed decreased signal intensity on T2-weighted images and measured 2.2 cm in size. The signal on T2-weighted images showed time-dependent decreases, and the mass continued to reduce in size throughout the follow-up period. The lesion presented as hypointense to the surrounding muscles on T2-weighted images and was 0.4 cm in size at 2 years of follow-up. This case demonstrates that nodular fasciitis with myxoid histology can change to that with fibrous appearance gradually with time, thus bringing about spontaneous regression. Degeneration may be involved in the spontaneous regression of nodular fasciitis with myxoid appearance. The mechanism of regression, unclarified at present, should be further studied. PMID:18650753

  10. A New Sample Size Formula for Regression.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.; Barcikowski, Robert S.

    The focus of this research was to determine the efficacy of a new method of selecting sample sizes for multiple linear regression. A Monte Carlo simulation was used to study both empirical predictive power rates and empirical statistical power rates of the new method and seven other methods: those of C. N. Park and A. L. Dudycha (1974); J. Cohen…

  11. Prediction of dynamical systems by symbolic regression.

    PubMed

    Quade, Markus; Abel, Markus; Shafi, Kamran; Niven, Robert K; Noack, Bernd R

    2016-07-01

    We study the modeling and prediction of dynamical systems based on conventional models derived from measurements. Such algorithms are highly desirable in situations where the underlying dynamics are hard to model from physical principles or simplified models need to be found. We focus on symbolic regression methods as a part of machine learning. These algorithms are capable of learning an analytically tractable model from data, a highly valuable property. Symbolic regression methods can be considered as generalized regression methods. We investigate two particular algorithms, the so-called fast function extraction which is a generalized linear regression algorithm, and genetic programming which is a very general method. Both are able to combine functions in a certain way such that a good model for the prediction of the temporal evolution of a dynamical system can be identified. We illustrate the algorithms by finding a prediction for the evolution of a harmonic oscillator based on measurements, by detecting an arriving front in an excitable system, and as a real-world application, the prediction of solar power production based on energy production observations at a given site together with the weather forecast. PMID:27575130

  12. Assumptions of Multiple Regression: Correcting Two Misconceptions

    ERIC Educational Resources Information Center

    Williams, Matt N.; Gomez Grajales, Carlos Alberto; Kurkiewicz, Dason

    2013-01-01

    In 2002, an article entitled "Four assumptions of multiple regression that researchers should always test" by Osborne and Waters was published in "PARE." This article has gone on to be viewed more than 275,000 times (as of August 2013), and it is one of the first results displayed in a Google search for "regression…

  13. Commonality Analysis for the Regression Case.

    ERIC Educational Resources Information Center

    Murthy, Kavita

    Commonality analysis is a procedure for decomposing the coefficient of determination (R superscript 2) in multiple regression analyses into the percent of variance in the dependent variable associated with each independent variable uniquely, and the proportion of explained variance associated with the common effects of predictors in various…

  14. Method for nonlinear exponential regression analysis

    NASA Technical Reports Server (NTRS)

    Junkin, B. G.

    1972-01-01

    Two computer programs developed according to two general types of exponential models for conducting nonlinear exponential regression analysis are described. Least squares procedure is used in which the nonlinear problem is linearized by expanding in a Taylor series. Program is written in FORTRAN 5 for the Univac 1108 computer.

  15. Multiple Regression Analysis and Automatic Interaction Detection.

    ERIC Educational Resources Information Center

    Koplyay, Janos B.

    The Automatic Interaction Detector (AID) is discussed as to its usefulness in multiple regression analysis. The algorithm of AID-4 is a reversal of the model building process; it starts with the ultimate restricted model, namely, the whole group as a unit. By a unique splitting process maximizing the between sum of squares for the categories of…

  16. A Spline Regression Model for Latent Variables

    ERIC Educational Resources Information Center

    Harring, Jeffrey R.

    2014-01-01

    Spline (or piecewise) regression models have been used in the past to account for patterns in observed data that exhibit distinct phases. The changepoint or knot marking the shift from one phase to the other, in many applications, is an unknown parameter to be estimated. As an extension of this framework, this research considers modeling the…

  17. Regression Segmentation for M³ Spinal Images.

    PubMed

    Wang, Zhijie; Zhen, Xiantong; Tay, KengYeow; Osman, Said; Romano, Walter; Li, Shuo

    2015-08-01

    Clinical routine often requires to analyze spinal images of multiple anatomic structures in multiple anatomic planes from multiple imaging modalities (M(3)). Unfortunately, existing methods for segmenting spinal images are still limited to one specific structure, in one specific plane or from one specific modality (S(3)). In this paper, we propose a novel approach, Regression Segmentation, that is for the first time able to segment M(3) spinal images in one single unified framework. This approach formulates the segmentation task innovatively as a boundary regression problem: modeling a highly nonlinear mapping function from substantially diverse M(3) images directly to desired object boundaries. Leveraging the advancement of sparse kernel machines, regression segmentation is fulfilled by a multi-dimensional support vector regressor (MSVR) which operates in an implicit, high dimensional feature space where M(3) diversity and specificity can be systematically categorized, extracted, and handled. The proposed regression segmentation approach was thoroughly tested on images from 113 clinical subjects including both disc and vertebral structures, in both sagittal and axial planes, and from both MRI and CT modalities. The overall result reaches a high dice similarity index (DSI) 0.912 and a low boundary distance (BD) 0.928 mm. With our unified and expendable framework, an efficient clinical tool for M(3) spinal image segmentation can be easily achieved, and will substantially benefit the diagnosis and treatment of spinal diseases.

  18. Prediction of dynamical systems by symbolic regression

    NASA Astrophysics Data System (ADS)

    Quade, Markus; Abel, Markus; Shafi, Kamran; Niven, Robert K.; Noack, Bernd R.

    2016-07-01

    We study the modeling and prediction of dynamical systems based on conventional models derived from measurements. Such algorithms are highly desirable in situations where the underlying dynamics are hard to model from physical principles or simplified models need to be found. We focus on symbolic regression methods as a part of machine learning. These algorithms are capable of learning an analytically tractable model from data, a highly valuable property. Symbolic regression methods can be considered as generalized regression methods. We investigate two particular algorithms, the so-called fast function extraction which is a generalized linear regression algorithm, and genetic programming which is a very general method. Both are able to combine functions in a certain way such that a good model for the prediction of the temporal evolution of a dynamical system can be identified. We illustrate the algorithms by finding a prediction for the evolution of a harmonic oscillator based on measurements, by detecting an arriving front in an excitable system, and as a real-world application, the prediction of solar power production based on energy production observations at a given site together with the weather forecast.

  19. Using Regression Analysis: A Guided Tour.

    ERIC Educational Resources Information Center

    Shelton, Fred Ames

    1987-01-01

    Discusses the use and interpretation of multiple regression analysis with computer programs and presents a flow chart of the process. A general explanation of the flow chart is provided, followed by an example showing the development of a linear equation which could be used in estimating manufacturing overhead cost. (Author/LRW)

  20. Genetic Programming Transforms in Linear Regression Situations

    NASA Astrophysics Data System (ADS)

    Castillo, Flor; Kordon, Arthur; Villa, Carlos

    The chapter summarizes the use of Genetic Programming (GP) inMultiple Linear Regression (MLR) to address multicollinearity and Lack of Fit (LOF). The basis of the proposed method is applying appropriate input transforms (model respecification) that deal with these issues while preserving the information content of the original variables. The transforms are selected from symbolic regression models with optimal trade-off between accuracy of prediction and expressional complexity, generated by multiobjective Pareto-front GP. The chapter includes a comparative study of the GP-generated transforms with Ridge Regression, a variant of ordinary Multiple Linear Regression, which has been a useful and commonly employed approach for reducing multicollinearity. The advantages of GP-generated model respecification are clearly defined and demonstrated. Some recommendations for transforms selection are given as well. The application benefits of the proposed approach are illustrated with a real industrial application in one of the broadest empirical modeling areas in manufacturing - robust inferential sensors. The chapter contributes to increasing the awareness of the potential of GP in statistical model building by MLR.

  1. The M Word: Multicollinearity in Multiple Regression.

    ERIC Educational Resources Information Center

    Morrow-Howell, Nancy

    1994-01-01

    Notes that existence of substantial correlation between two or more independent variables creates problems of multicollinearity in multiple regression. Discusses multicollinearity problem in social work research in which independent variables are usually intercorrelated. Clarifies problems created by multicollinearity, explains detection of…

  2. Revisiting Regression in Autism: Heller's "Dementia Infantilis"

    ERIC Educational Resources Information Center

    Westphal, Alexander; Schelinski, Stefanie; Volkmar, Fred; Pelphrey, Kevin

    2013-01-01

    Theodor Heller first described a severe regression of adaptive function in normally developing children, something he termed dementia infantilis, over one 100 years ago. Dementia infantilis is most closely related to the modern diagnosis, childhood disintegrative disorder. We translate Heller's paper, Uber Dementia Infantilis, and discuss…

  3. Prediction of dynamical systems by symbolic regression.

    PubMed

    Quade, Markus; Abel, Markus; Shafi, Kamran; Niven, Robert K; Noack, Bernd R

    2016-07-01

    We study the modeling and prediction of dynamical systems based on conventional models derived from measurements. Such algorithms are highly desirable in situations where the underlying dynamics are hard to model from physical principles or simplified models need to be found. We focus on symbolic regression methods as a part of machine learning. These algorithms are capable of learning an analytically tractable model from data, a highly valuable property. Symbolic regression methods can be considered as generalized regression methods. We investigate two particular algorithms, the so-called fast function extraction which is a generalized linear regression algorithm, and genetic programming which is a very general method. Both are able to combine functions in a certain way such that a good model for the prediction of the temporal evolution of a dynamical system can be identified. We illustrate the algorithms by finding a prediction for the evolution of a harmonic oscillator based on measurements, by detecting an arriving front in an excitable system, and as a real-world application, the prediction of solar power production based on energy production observations at a given site together with the weather forecast.

  4. Design Coding and Interpretation in Multiple Regression.

    ERIC Educational Resources Information Center

    Lunneborg, Clifford E.

    The multiple regression or general linear model (GLM) is a parameter estimation and hypothesis testing model which encompasses and approaches the more familiar fixed effects analysis of variance (ANOVA). The transition from ANOVA to GLM is accomplished, roughly, by coding treatment level or group membership to produce a set of predictor or…

  5. Predicting Social Trust with Binary Logistic Regression

    ERIC Educational Resources Information Center

    Adwere-Boamah, Joseph; Hufstedler, Shirley

    2015-01-01

    This study used binary logistic regression to predict social trust with five demographic variables from a national sample of adult individuals who participated in The General Social Survey (GSS) in 2012. The five predictor variables were respondents' highest degree earned, race, sex, general happiness and the importance of personally assisting…

  6. Code System to Calculate Correlation & Regression Coefficients.

    1999-11-23

    Version 00 PCC/SRC is designed for use in conjunction with sensitivity analyses of complex computer models. PCC/SRC calculates the partial correlation coefficients (PCC) and the standardized regression coefficients (SRC) from the multivariate input to, and output from, a computer model.

  7. A simple approach to power and sample size calculations in logistic regression and Cox regression models.

    PubMed

    Vaeth, Michael; Skovlund, Eva

    2004-06-15

    For a given regression problem it is possible to identify a suitably defined equivalent two-sample problem such that the power or sample size obtained for the two-sample problem also applies to the regression problem. For a standard linear regression model the equivalent two-sample problem is easily identified, but for generalized linear models and for Cox regression models the situation is more complicated. An approximately equivalent two-sample problem may, however, also be identified here. In particular, we show that for logistic regression and Cox regression models the equivalent two-sample problem is obtained by selecting two equally sized samples for which the parameters differ by a value equal to the slope times twice the standard deviation of the independent variable and further requiring that the overall expected number of events is unchanged. In a simulation study we examine the validity of this approach to power calculations in logistic regression and Cox regression models. Several different covariate distributions are considered for selected values of the overall response probability and a range of alternatives. For the Cox regression model we consider both constant and non-constant hazard rates. The results show that in general the approach is remarkably accurate even in relatively small samples. Some discrepancies are, however, found in small samples with few events and a highly skewed covariate distribution. Comparison with results based on alternative methods for logistic regression models with a single continuous covariate indicates that the proposed method is at least as good as its competitors. The method is easy to implement and therefore provides a simple way to extend the range of problems that can be covered by the usual formulas for power and sample size determination.

  8. Logistic models--an odd(s) kind of regression.

    PubMed

    Jupiter, Daniel C

    2013-01-01

    The logistic regression model bears some similarity to the multivariable linear regression with which we are familiar. However, the differences are great enough to warrant a discussion of the need for and interpretation of logistic regression.

  9. Embedded Sensors for Measuring Surface Regression

    NASA Technical Reports Server (NTRS)

    Gramer, Daniel J.; Taagen, Thomas J.; Vermaak, Anton G.

    2006-01-01

    The development and evaluation of new hybrid and solid rocket motors requires accurate characterization of the propellant surface regression as a function of key operational parameters. These characteristics establish the propellant flow rate and are prime design drivers affecting the propulsion system geometry, size, and overall performance. There is a similar need for the development of advanced ablative materials, and the use of conventional ablatives exposed to new operational environments. The Miniature Surface Regression Sensor (MSRS) was developed to serve these applications. It is designed to be cast or embedded in the material of interest and regresses along with it. During this process, the resistance of the sensor is related to its instantaneous length, allowing the real-time thickness of the host material to be established. The time derivative of this data reveals the instantaneous surface regression rate. The MSRS could also be adapted to perform similar measurements for a variety of other host materials when it is desired to monitor thicknesses and/or regression rate for purposes of safety, operational control, or research. For example, the sensor could be used to monitor the thicknesses of brake linings or racecar tires and indicate when they need to be replaced. At the time of this reporting, over 200 of these sensors have been installed into a variety of host materials. An MSRS can be made in either of two configurations, denoted ladder and continuous (see Figure 1). A ladder MSRS includes two highly electrically conductive legs, across which narrow strips of electrically resistive material are placed at small increments of length. These strips resemble the rungs of a ladder and are electrically equivalent to many tiny resistors connected in parallel. A substrate material provides structural support for the legs and rungs. The instantaneous sensor resistance is read by an external signal conditioner via wires attached to the conductive legs on the

  10. Progression and regression of the atherosclerotic plaque.

    PubMed

    de Feyter, P J; Vos, J; Deckers, J W

    1995-08-01

    In animals in which atherosclerosis was induced experimentally (by a high cholesterol diet) regression of the atherosclerotic lesion was demonstrated after serum cholesterol was reduced by cholesterol- lowering drugs or a low-fat diet. Whether regression of advanced coronary arterly lesions also takes place in humans after a similar intervention remains conjectural. However, several randomized studies, primarily employing lipid-lowering intervention or comprehensive changes in lifestyle, have demonstrated, using serial angiograms, that it is possible to achieve less progression, arrest or even (small) regression of atherosclerotic lesions. The lipid-lowering trials (NHBLI, CLAS, POSCH, FATS, SCOR and STARS) studied 1240 symptomatic patients, mostly men, with moderately elevated cholesterol levels and moderately severe angiographic-proven coronary artery disease. A variety of lipid-lowering drugs, in addition to a diet, were used over an intervention period ranging from 2 to 3 years. In all but one study (NHBLI), the progression of coronary atherosclerosis was less in the treated group, but regression was induced in only a few patients. The overall relative risk of progression of coronary atherosclerosis was 0 x 62 and 2 x 13, respectively. The induced angiographic differences were small and did not produce any significant haemodynamic benefit. The most important result was tht the disease process could be stabilized in the majority of patients. Three comprehensive lifestyle change trials (the Lifestyle Heart study, STARS and the Heidelberg Study) studied 183 patients, who were subjected to stress management, and/or intensive exercise, in addition to a low fat diet, over a period ranging from 1 to 3 years. All three trials demonstrated less progression, and more regression with overall relative risks of 0 x 40 and 2 x 35 respectively, in the intervention groups. Angiographic trials demonstrated that retardation or arrest of coronary atherosclerosis was possible

  11. Representation of exposures in regression analysis and interpretation of regression coefficients: basic concepts and pitfalls.

    PubMed

    Leffondré, Karen; Jager, Kitty J; Boucquemont, Julie; Stel, Vianda S; Heinze, Georg

    2014-10-01

    Regression models are being used to quantify the effect of an exposure on an outcome, while adjusting for potential confounders. While the type of regression model to be used is determined by the nature of the outcome variable, e.g. linear regression has to be applied for continuous outcome variables, all regression models can handle any kind of exposure variables. However, some fundamentals of representation of the exposure in a regression model and also some potential pitfalls have to be kept in mind in order to obtain meaningful interpretation of results. The objective of this educational paper was to illustrate these fundamentals and pitfalls, using various multiple regression models applied to data from a hypothetical cohort of 3000 patients with chronic kidney disease. In particular, we illustrate how to represent different types of exposure variables (binary, categorical with two or more categories and continuous), and how to interpret the regression coefficients in linear, logistic and Cox models. We also discuss the linearity assumption in these models, and show how wrongly assuming linearity may produce biased results and how flexible modelling using spline functions may provide better estimates.

  12. The comparison of robust partial least squares regression with robust principal component regression on a real

    NASA Astrophysics Data System (ADS)

    Polat, Esra; Gunay, Suleyman

    2013-10-01

    One of the problems encountered in Multiple Linear Regression (MLR) is multicollinearity, which causes the overestimation of the regression parameters and increase of the variance of these parameters. Hence, in case of multicollinearity presents, biased estimation procedures such as classical Principal Component Regression (CPCR) and Partial Least Squares Regression (PLSR) are then performed. SIMPLS algorithm is the leading PLSR algorithm because of its speed, efficiency and results are easier to interpret. However, both of the CPCR and SIMPLS yield very unreliable results when the data set contains outlying observations. Therefore, Hubert and Vanden Branden (2003) have been presented a robust PCR (RPCR) method and a robust PLSR (RPLSR) method called RSIMPLS. In RPCR, firstly, a robust Principal Component Analysis (PCA) method for high-dimensional data on the independent variables is applied, then, the dependent variables are regressed on the scores using a robust regression method. RSIMPLS has been constructed from a robust covariance matrix for high-dimensional data and robust linear regression. The purpose of this study is to show the usage of RPCR and RSIMPLS methods on an econometric data set, hence, making a comparison of two methods on an inflation model of Turkey. The considered methods have been compared in terms of predictive ability and goodness of fit by using a robust Root Mean Squared Error of Cross-validation (R-RMSECV), a robust R2 value and Robust Component Selection (RCS) statistic.

  13. Competing risks regression for clustered data.

    PubMed

    Zhou, Bingqing; Fine, Jason; Latouche, Aurelien; Labopin, Myriam

    2012-07-01

    A population average regression model is proposed to assess the marginal effects of covariates on the cumulative incidence function when there is dependence across individuals within a cluster in the competing risks setting. This method extends the Fine-Gray proportional hazards model for the subdistribution to situations, where individuals within a cluster may be correlated due to unobserved shared factors. Estimators of the regression parameters in the marginal model are developed under an independence working assumption where the correlation across individuals within a cluster is completely unspecified. The estimators are consistent and asymptotically normal, and variance estimation may be achieved without specifying the form of the dependence across individuals. A simulation study evidences that the inferential procedures perform well with realistic sample sizes. The practical utility of the methods is illustrated with data from the European Bone Marrow Transplant Registry.

  14. Competing risks regression for stratified data.

    PubMed

    Zhou, Bingqing; Latouche, Aurelien; Rocha, Vanderson; Fine, Jason

    2011-06-01

    For competing risks data, the Fine-Gray proportional hazards model for subdistribution has gained popularity for its convenience in directly assessing the effect of covariates on the cumulative incidence function. However, in many important applications, proportional hazards may not be satisfied, including multicenter clinical trials, where the baseline subdistribution hazards may not be common due to varying patient populations. In this article, we consider a stratified competing risks regression, to allow the baseline hazard to vary across levels of the stratification covariate. According to the relative size of the number of strata and strata sizes, two stratification regimes are considered. Using partial likelihood and weighting techniques, we obtain consistent estimators of regression parameters. The corresponding asymptotic properties and resulting inferences are provided for the two regimes separately. Data from a breast cancer clinical trial and from a bone marrow transplantation registry illustrate the potential utility of the stratified Fine-Gray model.

  15. Emptiness as defense in severe regressive states.

    PubMed

    LaFarge, L

    1989-01-01

    This paper examines the empty states experienced by severely ill borderline patients. At times of stressful regression, these patients use complaints of emptiness to describe profound disturbances of affect, cognition, object relations, and bodily experience. Empty states may be seen as complex defensive configurations which protect a borderline level of psychic structure from the impact of aggressively charged object relations, and ward off further regression to states of fragmentation or fusion. Severely ill borderline patients consolidate an empty screen by means of a characteristic repertoire of primitive defenses consisting of various forms of projective identification, including bitriangulation and projective identification of psychic agencies, somatization, acting out, and specific alterations in cognition. The author describes the highly deviant organizations of the object world seen in empty states, and the complex and disturbing countertransferences which these states evoke.

  16. Are increases in cigarette taxation regressive?

    PubMed

    Borren, P; Sutton, M

    1992-12-01

    Using the latest published data from Tobacco Advisory Council surveys, this paper re-evaluates the question of whether or not increases in cigarette taxation are regressive in the United Kingdom. The extended data set shows no evidence of increasing price-elasticity by social class as found in a major previous study. To the contrary, there appears to be no clear pattern in the price responsiveness of smoking behaviour across different social classes. Increases in cigarette taxation, while reducing smoking levels in all groups, fall most heavily on men and women in the lowest social class. Men and women in social class five can expect to pay eight and eleven times more of a tax increase respectively, than their social class one counterparts. Taken as a proportion of relative incomes, the regressive nature of increases in cigarette taxation is even more pronounced.

  17. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  18. Model selection for logistic regression models

    NASA Astrophysics Data System (ADS)

    Duller, Christine

    2012-09-01

    Model selection for logistic regression models decides which of some given potential regressors have an effect and hence should be included in the final model. The second interesting question is whether a certain factor is heterogeneous among some subsets, i.e. whether the model should include a random intercept or not. In this paper these questions will be answered with classical as well as with Bayesian methods. The application show some results of recent research projects in medicine and business administration.

  19. Differential correction schemes in nonlinear regression

    NASA Technical Reports Server (NTRS)

    Decell, H. P., Jr.; Speed, F. M.

    1972-01-01

    Classical iterative methods in nonlinear regression are reviewed and improved upon. This is accomplished by discussion of the geometrical and theoretical motivation for introducing modifications using generalized matrix inversion. Examples having inherent pitfalls are presented and compared in terms of results obtained using classical and modified techniques. The modification is shown to be useful alone or in conjunction with other modifications appearing in the literature.

  20. Modeling confounding by half-sibling regression.

    PubMed

    Schölkopf, Bernhard; Hogg, David W; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-07-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as "half-sibling regression," is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application.

  1. Modeling confounding by half-sibling regression

    PubMed Central

    Schölkopf, Bernhard; Hogg, David W.; Wang, Dun; Foreman-Mackey, Daniel; Janzing, Dominik; Simon-Gabriel, Carl-Johann; Peters, Jonas

    2016-01-01

    We describe a method for removing the effect of confounders to reconstruct a latent quantity of interest. The method, referred to as “half-sibling regression,” is inspired by recent work in causal inference using additive noise models. We provide a theoretical justification, discussing both independent and identically distributed as well as time series data, respectively, and illustrate the potential of the method in a challenging astronomy application. PMID:27382154

  2. Realization of Ridge Regression in MATLAB

    NASA Astrophysics Data System (ADS)

    Dimitrov, S.; Kovacheva, S.; Prodanova, K.

    2008-10-01

    The least square estimator (LSE) of the coefficients in the classical linear regression models is unbiased. In the case of multicollinearity of the vectors of design matrix, LSE has very big variance, i.e., the estimator is unstable. A more stable estimator (but biased) can be constructed using ridge-estimator (RE). In this paper the basic methods of obtaining of Ridge-estimators and numerical procedures of its realization in MATLAB are considered. An application to Pharmacokinetics problem is considered.

  3. Transfer Learning Based on Logistic Regression

    NASA Astrophysics Data System (ADS)

    Paul, A.; Rottensteiner, F.; Heipke, C.

    2015-08-01

    In this paper we address the problem of classification of remote sensing images in the framework of transfer learning with a focus on domain adaptation. The main novel contribution is a method for transductive transfer learning in remote sensing on the basis of logistic regression. Logistic regression is a discriminative probabilistic classifier of low computational complexity, which can deal with multiclass problems. This research area deals with methods that solve problems in which labelled training data sets are assumed to be available only for a source domain, while classification is needed in the target domain with different, yet related characteristics. Classification takes place with a model of weight coefficients for hyperplanes which separate features in the transformed feature space. In term of logistic regression, our domain adaptation method adjusts the model parameters by iterative labelling of the target test data set. These labelled data features are iteratively added to the current training set which, at the beginning, only contains source features and, simultaneously, a number of source features are deleted from the current training set. Experimental results based on a test series with synthetic and real data constitutes a first proof-of-concept of the proposed method.

  4. Face Alignment via Regressing Local Binary Features.

    PubMed

    Ren, Shaoqing; Cao, Xudong; Wei, Yichen; Sun, Jian

    2016-03-01

    This paper presents a highly efficient and accurate regression approach for face alignment. Our approach has two novel components: 1) a set of local binary features and 2) a locality principle for learning those features. The locality principle guides us to learn a set of highly discriminative local binary features for each facial landmark independently. The obtained local binary features are used to jointly learn a linear regression for the final output. This approach achieves the state-of-the-art results when tested on the most challenging benchmarks to date. Furthermore, because extracting and regressing local binary features are computationally very cheap, our system is much faster than previous methods. It achieves over 3000 frames per second (FPS) on a desktop or 300 FPS on a mobile phone for locating a few dozens of landmarks. We also study a key issue that is important but has received little attention in the previous research, which is the face detector used to initialize alignment. We investigate several face detectors and perform quantitative evaluation on how they affect alignment accuracy. We find that an alignment friendly detector can further greatly boost the accuracy of our alignment method, reducing the error up to 16% relatively. To facilitate practical usage of face detection/alignment methods, we also propose a convenient metric to measure how good a detector is for alignment initialization.

  5. Satellite rainfall retrieval by logistic regression

    NASA Technical Reports Server (NTRS)

    Chiu, Long S.

    1986-01-01

    The potential use of logistic regression in rainfall estimation from satellite measurements is investigated. Satellite measurements provide covariate information in terms of radiances from different remote sensors.The logistic regression technique can effectively accommodate many covariates and test their significance in the estimation. The outcome from the logistical model is the probability that the rainrate of a satellite pixel is above a certain threshold. By varying the thresholds, a rainrate histogram can be obtained, from which the mean and the variant can be estimated. A logistical model is developed and applied to rainfall data collected during GATE, using as covariates the fractional rain area and a radiance measurement which is deduced from a microwave temperature-rainrate relation. It is demonstrated that the fractional rain area is an important covariate in the model, consistent with the use of the so-called Area Time Integral in estimating total rain volume in other studies. To calibrate the logistical model, simulated rain fields generated by rainfield models with prescribed parameters are needed. A stringent test of the logistical model is its ability to recover the prescribed parameters of simulated rain fields. A rain field simulation model which preserves the fractional rain area and lognormality of rainrates as found in GATE is developed. A stochastic regression model of branching and immigration whose solutions are lognormally distributed in some asymptotic limits has also been developed.

  6. General Regression and Representation Model for Classification

    PubMed Central

    Qian, Jianjun; Yang, Jian; Xu, Yong

    2014-01-01

    Recently, the regularized coding-based classification methods (e.g. SRC and CRC) show a great potential for pattern classification. However, most existing coding methods assume that the representation residuals are uncorrelated. In real-world applications, this assumption does not hold. In this paper, we take account of the correlations of the representation residuals and develop a general regression and representation model (GRR) for classification. GRR not only has advantages of CRC, but also takes full use of the prior information (e.g. the correlations between representation residuals and representation coefficients) and the specific information (weight matrix of image pixels) to enhance the classification performance. GRR uses the generalized Tikhonov regularization and K Nearest Neighbors to learn the prior information from the training data. Meanwhile, the specific information is obtained by using an iterative algorithm to update the feature (or image pixel) weights of the test sample. With the proposed model as a platform, we design two classifiers: basic general regression and representation classifier (B-GRR) and robust general regression and representation classifier (R-GRR). The experimental results demonstrate the performance advantages of proposed methods over state-of-the-art algorithms. PMID:25531882

  7. Effect of Administration of Single Dose GnRH Agonist in Luteal Phase on Outcome of ICSI-ET Cycles in Women with Previous History of IVF/ICSI Failure: A Randomized Controlled Trial

    PubMed Central

    Zafardoust, Simin; Jeddi-Tehrani, Mahmood; Akhondi, Mohammad Mehdi; Sadeghi, Mohammad Reza; Kamali, Koroush; Mokhtar, Sara; Badehnoosh, Bita; Arjmand-Teymouri, Fatemeh; Fatemi, Farnaz; Mohammadzadeh, Afsaneh

    2015-01-01

    Background GnRH agonist administration in the luteal phase has been suggested to beneficially affect the outcome of intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) cycles. This blind randomized controlled study evaluates the effect of GnRH (Gonadotropine Releasing Hormone) agonist administration on ICSI outcome in GnRH antagonist ovarian stimulation protocol in women with 2 or more previous IVF/ICSI-ET failures. Methods One hundred IVF failure women who underwent ICSI cycles and stimulated with GnRH antagonist ovarian stimulation protocol, were included in the study. Women were randomly assigned to intervention (received a single dose injection of GnRH agonist (0.1 mg of Decapeptil) subcutaneously 6 days after oocyte retrieval) and control (did not receive GnRH agonist) groups. Implantation and clinical pregnancy rates were the primary outcome measures. Results Although the age of women, the number of embryos transferred in the current cycle and the quality of the transferred embryos were similar in the two groups, there was a significantly higher rate of implantation (Mann Whitney test, p = 0.041) and pregnancy (32.6% vs. 12.5%, p = 0.030, OR = 3.3, 95%CI, 1.08 to 10.4) in the intervention group. Conclusion Our results suggested that, in addition to routine luteal phase support using progesterone, administration of 0.1 mg of Decapeptil 6 days after oocyte retrieval in women with previous history of 2 or more IVF/ICSI failures led to a significant improvement in implantation and pregnancy rates after ICSI following ovarian stimulation with GnRH antagonist protocol. PMID:25927026

  8. Quantile regression modeling for Malaysian automobile insurance premium data

    NASA Astrophysics Data System (ADS)

    Fuzi, Mohd Fadzli Mohd; Ismail, Noriszura; Jemain, Abd Aziz

    2015-09-01

    Quantile regression is a robust regression to outliers compared to mean regression models. Traditional mean regression models like Generalized Linear Model (GLM) are not able to capture the entire distribution of premium data. In this paper we demonstrate how a quantile regression approach can be used to model net premium data to study the effects of change in the estimates of regression parameters (rating classes) on the magnitude of response variable (pure premium). We then compare the results of quantile regression model with Gamma regression model. The results from quantile regression show that some rating classes increase as quantile increases and some decrease with decreasing quantile. Further, we found that the confidence interval of median regression (τ = O.5) is always smaller than Gamma regression in all risk factors.

  9. Analyzing Historical Count Data: Poisson and Negative Binomial Regression Models.

    ERIC Educational Resources Information Center

    Beck, E. M.; Tolnay, Stewart E.

    1995-01-01

    Asserts that traditional approaches to multivariate analysis, including standard linear regression techniques, ignore the special character of count data. Explicates three suitable alternatives to standard regression techniques, a simple Poisson regression, a modified Poisson regression, and a negative binomial model. (MJP)

  10. The Regression Trunk Approach to Discover Treatment Covariate Interaction

    ERIC Educational Resources Information Center

    Dusseldorp, Elise; Meulman, Jacqueline J.

    2004-01-01

    The regression trunk approach (RTA) is an integration of regression trees and multiple linear regression analysis. In this paper RTA is used to discover treatment covariate interactions, in the regression of one continuous variable on a treatment variable with "multiple" covariates. The performance of RTA is compared to the classical method of…

  11. Multiple linear regression for isotopic measurements

    NASA Astrophysics Data System (ADS)

    Garcia Alonso, J. I.

    2012-04-01

    There are two typical applications of isotopic measurements: the detection of natural variations in isotopic systems and the detection man-made variations using enriched isotopes as indicators. For both type of measurements accurate and precise isotope ratio measurements are required. For the so-called non-traditional stable isotopes, multicollector ICP-MS instruments are usually applied. In many cases, chemical separation procedures are required before accurate isotope measurements can be performed. The off-line separation of Rb and Sr or Nd and Sm is the classical procedure employed to eliminate isobaric interferences before multicollector ICP-MS measurement of Sr and Nd isotope ratios. Also, this procedure allows matrix separation for precise and accurate Sr and Nd isotope ratios to be obtained. In our laboratory we have evaluated the separation of Rb-Sr and Nd-Sm isobars by liquid chromatography and on-line multicollector ICP-MS detection. The combination of this chromatographic procedure with multiple linear regression of the raw chromatographic data resulted in Sr and Nd isotope ratios with precisions and accuracies typical of off-line sample preparation procedures. On the other hand, methods for the labelling of individual organisms (such as a given plant, fish or animal) are required for population studies. We have developed a dual isotope labelling procedure which can be unique for a given individual, can be inherited in living organisms and it is stable. The detection of the isotopic signature is based also on multiple linear regression. The labelling of fish and its detection in otoliths by Laser Ablation ICP-MS will be discussed using trout and salmon as examples. As a conclusion, isotope measurement procedures based on multiple linear regression can be a viable alternative in multicollector ICP-MS measurements.

  12. Mapping geogenic radon potential by regression kriging.

    PubMed

    Pásztor, László; Szabó, Katalin Zsuzsanna; Szatmári, Gábor; Laborczi, Annamária; Horváth, Ákos

    2016-02-15

    Radon ((222)Rn) gas is produced in the radioactive decay chain of uranium ((238)U) which is an element that is naturally present in soils. Radon is transported mainly by diffusion and convection mechanisms through the soil depending mainly on the physical and meteorological parameters of the soil and can enter and accumulate in buildings. Health risks originating from indoor radon concentration can be attributed to natural factors and is characterized by geogenic radon potential (GRP). Identification of areas with high health risks require spatial modeling, that is, mapping of radon risk. In addition to geology and meteorology, physical soil properties play a significant role in the determination of GRP. In order to compile a reliable GRP map for a model area in Central-Hungary, spatial auxiliary information representing GRP forming environmental factors were taken into account to support the spatial inference of the locally measured GRP values. Since the number of measured sites was limited, efficient spatial prediction methodologies were searched for to construct a reliable map for a larger area. Regression kriging (RK) was applied for the interpolation using spatially exhaustive auxiliary data on soil, geology, topography, land use and climate. RK divides the spatial inference into two parts. Firstly, the deterministic component of the target variable is determined by a regression model. The residuals of the multiple linear regression analysis represent the spatially varying but dependent stochastic component, which are interpolated by kriging. The final map is the sum of the two component predictions. Overall accuracy of the map was tested by Leave-One-Out Cross-Validation. Furthermore the spatial reliability of the resultant map is also estimated by the calculation of the 90% prediction interval of the local prediction values. The applicability of the applied method as well as that of the map is discussed briefly. PMID:26706761

  13. Monthly streamflow forecasting using Gaussian Process Regression

    NASA Astrophysics Data System (ADS)

    Sun, Alexander Y.; Wang, Dingbao; Xu, Xianli

    2014-04-01

    Streamflow forecasting plays a critical role in nearly all aspects of water resources planning and management. In this work, Gaussian Process Regression (GPR), an effective kernel-based machine learning algorithm, is applied to probabilistic streamflow forecasting. GPR is built on Gaussian process, which is a stochastic process that generalizes multivariate Gaussian distribution to infinite-dimensional space such that distributions over function values can be defined. The GPR algorithm provides a tractable and flexible hierarchical Bayesian framework for inferring the posterior distribution of streamflows. The prediction skill of the algorithm is tested for one-month-ahead prediction using the MOPEX database, which includes long-term hydrometeorological time series collected from 438 basins across the U.S. from 1948 to 2003. Comparisons with linear regression and artificial neural network models indicate that GPR outperforms both regression methods in most cases. The GPR prediction of MOPEX basins is further examined using the Budyko framework, which helps to reveal the close relationships among water-energy partitions, hydrologic similarity, and predictability. Flow regime modification and the resulting loss of predictability have been a major concern in recent years because of climate change and anthropogenic activities. The persistence of streamflow predictability is thus examined by extending the original MOPEX data records to 2012. Results indicate relatively strong persistence of streamflow predictability in the extended period, although the low-predictability basins tend to show more variations. Because many low-predictability basins are located in regions experiencing fast growth of human activities, the significance of sustainable development and water resources management can be even greater for those regions.

  14. Mapping geogenic radon potential by regression kriging.

    PubMed

    Pásztor, László; Szabó, Katalin Zsuzsanna; Szatmári, Gábor; Laborczi, Annamária; Horváth, Ákos

    2016-02-15

    Radon ((222)Rn) gas is produced in the radioactive decay chain of uranium ((238)U) which is an element that is naturally present in soils. Radon is transported mainly by diffusion and convection mechanisms through the soil depending mainly on the physical and meteorological parameters of the soil and can enter and accumulate in buildings. Health risks originating from indoor radon concentration can be attributed to natural factors and is characterized by geogenic radon potential (GRP). Identification of areas with high health risks require spatial modeling, that is, mapping of radon risk. In addition to geology and meteorology, physical soil properties play a significant role in the determination of GRP. In order to compile a reliable GRP map for a model area in Central-Hungary, spatial auxiliary information representing GRP forming environmental factors were taken into account to support the spatial inference of the locally measured GRP values. Since the number of measured sites was limited, efficient spatial prediction methodologies were searched for to construct a reliable map for a larger area. Regression kriging (RK) was applied for the interpolation using spatially exhaustive auxiliary data on soil, geology, topography, land use and climate. RK divides the spatial inference into two parts. Firstly, the deterministic component of the target variable is determined by a regression model. The residuals of the multiple linear regression analysis represent the spatially varying but dependent stochastic component, which are interpolated by kriging. The final map is the sum of the two component predictions. Overall accuracy of the map was tested by Leave-One-Out Cross-Validation. Furthermore the spatial reliability of the resultant map is also estimated by the calculation of the 90% prediction interval of the local prediction values. The applicability of the applied method as well as that of the map is discussed briefly.

  15. Convex Regression with Interpretable Sharp Partitions

    PubMed Central

    Petersen, Ashley; Simon, Noah; Witten, Daniela

    2016-01-01

    We consider the problem of predicting an outcome variable on the basis of a small number of covariates, using an interpretable yet non-additive model. We propose convex regression with interpretable sharp partitions (CRISP) for this task. CRISP partitions the covariate space into blocks in a data-adaptive way, and fits a mean model within each block. Unlike other partitioning methods, CRISP is fit using a non-greedy approach by solving a convex optimization problem, resulting in low-variance fits. We explore the properties of CRISP, and evaluate its performance in a simulation study and on a housing price data set.

  16. A method for nonlinear exponential regression analysis

    NASA Technical Reports Server (NTRS)

    Junkin, B. G.

    1971-01-01

    A computer-oriented technique is presented for performing a nonlinear exponential regression analysis on decay-type experimental data. The technique involves the least squares procedure wherein the nonlinear problem is linearized by expansion in a Taylor series. A linear curve fitting procedure for determining the initial nominal estimates for the unknown exponential model parameters is included as an integral part of the technique. A correction matrix was derived and then applied to the nominal estimate to produce an improved set of model parameters. The solution cycle is repeated until some predetermined criterion is satisfied.

  17. SPE dose prediction using locally weighted regression.

    PubMed

    Hines, J W; Townsend, L W; Nichols, T F

    2005-01-01

    When astronauts are outside Earth's protective magnetosphere, they are subject to large radiation doses resulting from solar particle events. The total dose received from a major solar particle event in deep space could cause severe radiation poisoning. The dose is usually received over a 20-40 h time interval but the event's effects may be reduced with an early warning system. This paper presents a method to predict the total dose early in the event. It uses a locally weighted regression model, which is easier to train, and provides predictions as accurate as the neural network models that were used previously. PMID:16604613

  18. An operational GLS model for hydrologic regression

    USGS Publications Warehouse

    Tasker, Gary D.; Stedinger, J.R.

    1989-01-01

    Recent Monte Carlo studies have documented the value of generalized least squares (GLS) procedures to estimate empirical relationships between streamflow statistics and physiographic basin characteristics. This paper presents a number of extensions of the GLS method that deal with realities and complexities of regional hydrologic data sets that were not addressed in the simulation studies. These extensions include: (1) a more realistic model of the underlying model errors; (2) smoothed estimates of cross correlation of flows; (3) procedures for including historical flow data; (4) diagnostic statistics describing leverage and influence for GLS regression; and (5) the formulation of a mathematical program for evaluating future gaging activities. ?? 1989.

  19. Convex Regression with Interpretable Sharp Partitions

    PubMed Central

    Petersen, Ashley; Simon, Noah; Witten, Daniela

    2016-01-01

    We consider the problem of predicting an outcome variable on the basis of a small number of covariates, using an interpretable yet non-additive model. We propose convex regression with interpretable sharp partitions (CRISP) for this task. CRISP partitions the covariate space into blocks in a data-adaptive way, and fits a mean model within each block. Unlike other partitioning methods, CRISP is fit using a non-greedy approach by solving a convex optimization problem, resulting in low-variance fits. We explore the properties of CRISP, and evaluate its performance in a simulation study and on a housing price data set. PMID:27635120

  20. Triton,... electron,... cosmon,...: An infinite regression?

    PubMed

    Dehmelt, H

    1989-11-01

    I propose an elementary particle model in which the simplest near-Dirac particles triton, proton, and electron are members of the three top layers of a bottomless stack. Each particle is a composite of three particles from the next layer below in an infinite regression approaching Dirac point particles. The cosmon, an immensely heavy lower layer subquark, is the elementary particle. The world-atom, a tightly bound cosmon/anticosmon pair of zero relativistic total mass, arose from the nothing state in a quantum jump. Rapid decay of the pair launched the big bang and created the universe. PMID:16594084

  1. Significant Scoliosis Regression following Syringomyelia Decompression

    PubMed Central

    Mollano, Anthony V; Weinstein, Stuart L; Menezes, Arnold H

    2005-01-01

    We present the case of a 5-year-old boy presenting with a 54-degree scoliosis secondary to a Chiari I malformation with a holocord syringomyelia extending from C1 to T10. Neurosurgical treatment involved posterior fossa craniectomy with decompression, and partial C1 laminectomy. At follow-up 7 years later, at age 12, radiographs revealed only a 4-degree scoliosis, and follow-up MRI revealed a deflated syrinx. We report this case to reveal the most significant scoliosis regression seen in our experience that may occur in younger patients after neurosurgical syringomyelia decompression for Chiari I hindbrain herniation. PMID:16089074

  2. An Investigation of Sleep Characteristics, EEG Abnormalities and Epilepsy in Developmentally Regressed and Non-Regressed Children with Autism

    ERIC Educational Resources Information Center

    Giannotti, Flavia; Cortesi, Flavia; Cerquiglini, Antonella; Miraglia, Daniela; Vagnoni, Cristina; Sebastiani, Teresa; Bernabei, Paola

    2008-01-01

    This study investigated sleep of children with autism and developmental regression and the possible relationship with epilepsy and epileptiform abnormalities. Participants were 104 children with autism (70 non-regressed, 34 regressed) and 162 typically developing children (TD). Results suggested that the regressed group had higher incidence of…

  3. Shape regression for vertebra fracture quantification

    NASA Astrophysics Data System (ADS)

    Lund, Michael Tillge; de Bruijne, Marleen; Tanko, Laszlo B.; Nielsen, Mads

    2005-04-01

    Accurate and reliable identification and quantification of vertebral fractures constitute a challenge both in clinical trials and in diagnosis of osteoporosis. Various efforts have been made to develop reliable, objective, and reproducible methods for assessing vertebral fractures, but at present there is no consensus concerning a universally accepted diagnostic definition of vertebral fractures. In this project we want to investigate whether or not it is possible to accurately reconstruct the shape of a normal vertebra, using a neighbouring vertebra as prior information. The reconstructed shape can then be used to develop a novel vertebra fracture measure, by comparing the segmented vertebra shape with its reconstructed normal shape. The vertebrae in lateral x-rays of the lumbar spine were manually annotated by a medical expert. With this dataset we built a shape model, with equidistant point distribution between the four corner points. Based on the shape model, a multiple linear regression model of a normal vertebra shape was developed for each dataset using leave-one-out cross-validation. The reconstructed shape was calculated for each dataset using these regression models. The average prediction error for the annotated shape was on average 3%.

  4. A Gibbs sampler for multivariate linear regression

    NASA Astrophysics Data System (ADS)

    Mantz, Adam B.

    2016-04-01

    Kelly described an efficient algorithm, using Gibbs sampling, for performing linear regression in the fairly general case where non-zero measurement errors exist for both the covariates and response variables, where these measurements may be correlated (for the same data point), where the response variable is affected by intrinsic scatter in addition to measurement error, and where the prior distribution of covariates is modelled by a flexible mixture of Gaussians rather than assumed to be uniform. Here, I extend the Kelly algorithm in two ways. First, the procedure is generalized to the case of multiple response variables. Secondly, I describe how to model the prior distribution of covariates using a Dirichlet process, which can be thought of as a Gaussian mixture where the number of mixture components is learned from the data. I present an example of multivariate regression using the extended algorithm, namely fitting scaling relations of the gas mass, temperature, and luminosity of dynamically relaxed galaxy clusters as a function of their mass and redshift. An implementation of the Gibbs sampler in the R language, called LRGS, is provided.

  5. Supporting Regularized Logistic Regression Privately and Efficiently

    PubMed Central

    Li, Wenfa; Liu, Hongzhe; Yang, Peng; Xie, Wei

    2016-01-01

    As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc. PMID:27271738

  6. Regression Analysis Of Zernike Polynomials Part II

    NASA Astrophysics Data System (ADS)

    Grey, Louis D.

    1989-01-01

    In an earlier paper entitled "Regression Analysis of Zernike Polynomials, Proceedings of SPIE, Vol. 18, pp. 392-398, the least squares fitting process of Zernike polynomials was examined from the point of view of linear statistical regression theory. Among the topics discussed were measures for determining how good the fit was, tests for the underlying assumptions of normality and constant variance, the treatment of outliers, the analysis of residuals and the computation of confidence intervals for the coefficients. The present paper is a continuation of the earlier paper and concerns applications of relatively new advances in certain areas of statistical theory made possible by the advent of the high speed computer. Among these are: 1. Jackknife - A technique for improving the accuracy of any statistical estimate. 2. Bootstrap - Increasing the accuracy of an estimate by generating new samples of data from some given set. 3. Cross-validation - The division of a data set into two halves, the first half of which is used to fit the model and the second half to see how well the fitted model predicts the data. The exposition is mainly by examples.

  7. Supporting Regularized Logistic Regression Privately and Efficiently.

    PubMed

    Li, Wenfa; Liu, Hongzhe; Yang, Peng; Xie, Wei

    2016-01-01

    As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc. PMID:27271738

  8. Supporting Regularized Logistic Regression Privately and Efficiently.

    PubMed

    Li, Wenfa; Liu, Hongzhe; Yang, Peng; Xie, Wei

    2016-01-01

    As one of the most popular statistical and machine learning models, logistic regression with regularization has found wide adoption in biomedicine, social sciences, information technology, and so on. These domains often involve data of human subjects that are contingent upon strict privacy regulations. Concerns over data privacy make it increasingly difficult to coordinate and conduct large-scale collaborative studies, which typically rely on cross-institution data sharing and joint analysis. Our work here focuses on safeguarding regularized logistic regression, a widely-used statistical model while at the same time has not been investigated from a data security and privacy perspective. We consider a common use scenario of multi-institution collaborative studies, such as in the form of research consortia or networks as widely seen in genetics, epidemiology, social sciences, etc. To make our privacy-enhancing solution practical, we demonstrate a non-conventional and computationally efficient method leveraging distributing computing and strong cryptography to provide comprehensive protection over individual-level and summary data. Extensive empirical evaluations on several studies validate the privacy guarantee, efficiency and scalability of our proposal. We also discuss the practical implications of our solution for large-scale studies and applications from various disciplines, including genetic and biomedical studies, smart grid, network analysis, etc.

  9. Jackknife bias reduction for polychotomous logistic regression.

    PubMed

    Bull, S B; Greenwood, C M; Hauck, W W

    1997-03-15

    Despite theoretical and empirical evidence that the usual MLEs can be misleading in finite samples and some evidence that bias reduced estimates are less biased and more efficient, they have not seen a wide application in practice. One can obtain bias reduced estimates by jackknife methods, with or without full iteration, or by use of higher order terms in a Taylor series expansion of the log-likelihood to approximate asymptotic bias. We provide details of these methods for polychotomous logistic regression with a nominal categorical response. We conducted a Monte Carlo comparison of the jackknife and Taylor series estimates in moderate sample sizes in a general logistic regression setting, to investigate dichotomous and trichotomous responses and a mixture of correlated and uncorrelated binary and normal covariates. We found an approximate two-step jackknife and the Taylor series methods useful when the ratio of the number of observations to the number of parameters is greater than 15, but we cannot recommend the two-step and the fully iterated jackknife estimates when this ratio is less than 20, especially when there are large effects, binary covariates, or multicollinearity in the covariates.

  10. Regression Models For Saffron Yields in Iran

    NASA Astrophysics Data System (ADS)

    S. H, Sanaeinejad; S. N, Hosseini

    Saffron is an important crop in social and economical aspects in Khorassan Province (Northeast of Iran). In this research wetried to evaluate trends of saffron yield in recent years and to study the relationship between saffron yield and the climate change. A regression analysis was used to predict saffron yield based on 20 years of yield data in Birjand, Ghaen and Ferdows cities.Climatologically data for the same periods was provided by database of Khorassan Climatology Center. Climatologically data includedtemperature, rainfall, relative humidity and sunshine hours for ModelI, and temperature and rainfall for Model II. The results showed the coefficients of determination for Birjand, Ferdows and Ghaen for Model I were 0.69, 0.50 and 0.81 respectively. Also coefficients of determination for the same cities for model II were 0.53, 0.50 and 0.72 respectively. Multiple regression analysisindicated that among weather variables, temperature was the key parameter for variation ofsaffron yield. It was concluded that increasing temperature at spring was the main cause of declined saffron yield during recent years across the province. Finally, yield trend was predicted for the last 5 years using time series analysis.

  11. Biological Parametric Mapping Accounting for Random Regressors with Regression Calibration and Model II Regression

    PubMed Central

    Yang, Xue; Lauzon, Carolyn B.; Crainiceanu, Ciprian; Caffo, Brian; Resnick, Susan M.; Landman, Bennett A.

    2012-01-01

    Massively univariate regression and inference in the form of statistical parametric mapping have transformed the way in which multi-dimensional imaging data are studied. In functional and structural neuroimaging, the de facto standard “design matrix”-based general linear regression model and its multi-level cousins have enabled investigation of the biological basis of the human brain. With modern study designs, it is possible to acquire multi-modal three-dimensional assessments of the same individuals — e.g., structural, functional and quantitative magnetic resonance imaging, alongside functional and ligand binding maps with positron emission tomography. Largely, current statistical methods in the imaging community assume that the regressors are non-random. For more realistic multi-parametric assessment (e.g., voxel-wise modeling), distributional consideration of all observations is appropriate. Herein, we discuss two unified regression and inference approaches, model II regression and regression calibration, for use in massively univariate inference with imaging data. These methods use the design matrix paradigm and account for both random and non-random imaging regressors. We characterize these methods in simulation and illustrate their use on an empirical dataset. Both methods have been made readily available as a toolbox plug-in for the SPM software. PMID:22609453

  12. Multicollinearity and correlation among local regression coefficients in geographically weighted regression

    NASA Astrophysics Data System (ADS)

    Wheeler, David; Tiefelsdorf, Michael

    2005-06-01

    Present methodological research on geographically weighted regression (GWR) focuses primarily on extensions of the basic GWR model, while ignoring well-established diagnostics tests commonly used in standard global regression analysis. This paper investigates multicollinearity issues surrounding the local GWR coefficients at a single location and the overall correlation between GWR coefficients associated with two different exogenous variables. Results indicate that the local regression coefficients are potentially collinear even if the underlying exogenous variables in the data generating process are uncorrelated. Based on these findings, applied GWR research should practice caution in substantively interpreting the spatial patterns of local GWR coefficients. An empirical disease-mapping example is used to motivate the GWR multicollinearity problem. Controlled experiments are performed to systematically explore coefficient dependency issues in GWR. These experiments specify global models that use eigenvectors from a spatial link matrix as exogenous variables.

  13. Tolerance bounds for log gamma regression models

    NASA Technical Reports Server (NTRS)

    Jones, R. A.; Scholz, F. W.; Ossiander, M.; Shorack, G. R.

    1985-01-01

    The present procedure for finding lower confidence bounds for the quantiles of Weibull populations, on the basis of the solution of a quadratic equation, is more accurate than current Monte Carlo tables and extends to any location-scale family. It is shown that this method is accurate for all members of the log gamma(K) family, where K = 1/2 to infinity, and works well for censored data, while also extending to regression data. An even more accurate procedure involving an approximation to the Lawless (1982) conditional procedure, with numerical integrations whose tables are independent of the data, is also presented. These methods are applied to the case of failure strengths of ceramic specimens from each of three billets of Si3N4, which have undergone flexural strength testing.

  14. Sparse brain network using penalized linear regression

    NASA Astrophysics Data System (ADS)

    Lee, Hyekyoung; Lee, Dong Soo; Kang, Hyejin; Kim, Boong-Nyun; Chung, Moo K.

    2011-03-01

    Sparse partial correlation is a useful connectivity measure for brain networks when it is difficult to compute the exact partial correlation in the small-n large-p setting. In this paper, we formulate the problem of estimating partial correlation as a sparse linear regression with a l1-norm penalty. The method is applied to brain network consisting of parcellated regions of interest (ROIs), which are obtained from FDG-PET images of the autism spectrum disorder (ASD) children and the pediatric control (PedCon) subjects. To validate the results, we check their reproducibilities of the obtained brain networks by the leave-one-out cross validation and compare the clustered structures derived from the brain networks of ASD and PedCon.

  15. Macrophages, dendritic cells, and regression of atherosclerosis.

    PubMed

    Feig, Jonathan E; Feig, Jessica L

    2012-01-01

    Atherosclerosis is the number one cause of death in the Western world. It results from the interaction between modified lipoproteins and cells such as macrophages, dendritic cells (DCs), T cells, and other cellular elements present in the arterial wall. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, that protrude into the arterial lumen. Ultimately, plaque rupture and thrombosis can occur leading to the clinical complications of myocardial infarction or stroke. Although each of the cell types plays roles in the pathogenesis of atherosclerosis, the focus of this review will be primarily on the macrophages and DCs. The role of these two cell types in atherosclerosis is discussed, with a particular emphasis on their involvement in atherosclerosis regression.

  16. [Logistic regression against a divergent Bayesian network].

    PubMed

    Sánchez Trujillo, Noel Antonio

    2015-02-03

    This article is a discussion about two statistical tools used for prediction and causality assessment: logistic regression and Bayesian networks. Using data of a simulated example from a study assessing factors that might predict pulmonary emphysema (where fingertip pigmentation and smoking are considered); we posed the following questions. Is pigmentation a confounding, causal or predictive factor? Is there perhaps another factor, like smoking, that confounds? Is there a synergy between pigmentation and smoking? The results, in terms of prediction, are similar with the two techniques; regarding causation, differences arise. We conclude that, in decision-making, the sum of both: a statistical tool, used with common sense, and previous evidence, taking years or even centuries to develop; is better than the automatic and exclusive use of statistical resources.

  17. Support vector machines for classification and regression.

    PubMed

    Brereton, Richard G; Lloyd, Gavin R

    2010-02-01

    The increasing interest in Support Vector Machines (SVMs) over the past 15 years is described. Methods are illustrated using simulated case studies, and 4 experimental case studies, namely mass spectrometry for studying pollution, near infrared analysis of food, thermal analysis of polymers and UV/visible spectroscopy of polyaromatic hydrocarbons. The basis of SVMs as two-class classifiers is shown with extensive visualisation, including learning machines, kernels and penalty functions. The influence of the penalty error and radial basis function radius on the model is illustrated. Multiclass implementations including one vs. all, one vs. one, fuzzy rules and Directed Acyclic Graph (DAG) trees are described. One-class Support Vector Domain Description (SVDD) is described and contrasted to conventional two- or multi-class classifiers. The use of Support Vector Regression (SVR) is illustrated including its application to multivariate calibration, and why it is useful when there are outliers and non-linearities.

  18. Estimates on compressed neural networks regression.

    PubMed

    Zhang, Yongquan; Li, Youmei; Sun, Jianyong; Ji, Jiabing

    2015-03-01

    When the neural element number n of neural networks is larger than the sample size m, the overfitting problem arises since there are more parameters than actual data (more variable than constraints). In order to overcome the overfitting problem, we propose to reduce the number of neural elements by using compressed projection A which does not need to satisfy the condition of Restricted Isometric Property (RIP). By applying probability inequalities and approximation properties of the feedforward neural networks (FNNs), we prove that solving the FNNs regression learning algorithm in the compressed domain instead of the original domain reduces the sample error at the price of an increased (but controlled) approximation error, where the covering number theory is used to estimate the excess error, and an upper bound of the excess error is given.

  19. Collaborative regression-based anatomical landmark detection

    NASA Astrophysics Data System (ADS)

    Gao, Yaozong; Shen, Dinggang

    2015-12-01

    Anatomical landmark detection plays an important role in medical image analysis, e.g. for registration, segmentation and quantitative analysis. Among the various existing methods for landmark detection, regression-based methods have recently attracted much attention due to their robustness and efficiency. In these methods, landmarks are localised through voting from all image voxels, which is completely different from the classification-based methods that use voxel-wise classification to detect landmarks. Despite their robustness, the accuracy of regression-based landmark detection methods is often limited due to (1) the inclusion of uninformative image voxels in the voting procedure, and (2) the lack of effective ways to incorporate inter-landmark spatial dependency into the detection step. In this paper, we propose a collaborative landmark detection framework to address these limitations. The concept of collaboration is reflected in two aspects. (1) Multi-resolution collaboration. A multi-resolution strategy is proposed to hierarchically localise landmarks by gradually excluding uninformative votes from faraway voxels. Moreover, for informative voxels near the landmark, a spherical sampling strategy is also designed at the training stage to improve their prediction accuracy. (2) Inter-landmark collaboration. A confidence-based landmark detection strategy is proposed to improve the detection accuracy of ‘difficult-to-detect’ landmarks by using spatial guidance from ‘easy-to-detect’ landmarks. To evaluate our method, we conducted experiments extensively on three datasets for detecting prostate landmarks and head & neck landmarks in computed tomography images, and also dental landmarks in cone beam computed tomography images. The results show the effectiveness of our collaborative landmark detection framework in improving landmark detection accuracy, compared to other state-of-the-art methods.

  20. Computing confidence intervals for standardized regression coefficients.

    PubMed

    Jones, Jeff A; Waller, Niels G

    2013-12-01

    With fixed predictors, the standard method (Cohen, Cohen, West, & Aiken, 2003, p. 86; Harris, 2001, p. 80; Hays, 1994, p. 709) for computing confidence intervals (CIs) for standardized regression coefficients fails to account for the sampling variability of the criterion standard deviation. With random predictors, this method also fails to account for the sampling variability of the predictor standard deviations. Nevertheless, under some conditions the standard method will produce CIs with accurate coverage rates. To delineate these conditions, we used a Monte Carlo simulation to compute empirical CI coverage rates in samples drawn from 36 populations with a wide range of data characteristics. We also computed the empirical CI coverage rates for 4 alternative methods that have been discussed in the literature: noncentrality interval estimation, the delta method, the percentile bootstrap, and the bias-corrected and accelerated bootstrap. Our results showed that for many data-parameter configurations--for example, sample size, predictor correlations, coefficient of determination (R²), orientation of β with respect to the eigenvectors of the predictor correlation matrix, RX--the standard method produced coverage rates that were close to their expected values. However, when population R² was large and when β approached the last eigenvector of RX, then the standard method coverage rates were frequently below the nominal rate (sometimes by a considerable amount). In these conditions, the delta method and the 2 bootstrap procedures were consistently accurate. Results using noncentrality interval estimation were inconsistent. In light of these findings, we recommend that researchers use the delta method to evaluate the sampling variability of standardized regression coefficients.

  1. Logistic Regression Applied to Seismic Discrimination

    SciTech Connect

    BG Amindan; DN Hagedorn

    1998-10-08

    The usefulness of logistic discrimination was examined in an effort to learn how it performs in a regional seismic setting. Logistic discrimination provides an easily understood method, works with user-defined models and few assumptions about the population distributions, and handles both continuous and discrete data. Seismic event measurements from a data set compiled by Los Alamos National Laboratory (LANL) of Chinese events recorded at station WMQ were used in this demonstration study. PNNL applied logistic regression techniques to the data. All possible combinations of the Lg and Pg measurements were tried, and a best-fit logistic model was created. The best combination of Lg and Pg frequencies for predicting the source of a seismic event (earthquake or explosion) used Lg{sub 3.0-6.0} and Pg{sub 3.0-6.0} as the predictor variables. A cross-validation test was run, which showed that this model was able to correctly predict 99.7% earthquakes and 98.0% explosions for this given data set. Two other models were identified that used Pg and Lg measurements from the 1.5 to 3.0 Hz frequency range. Although these other models did a good job of correctly predicting the earthquakes, they were not as effective at predicting the explosions. Two possible biases were discovered which affect the predicted probabilities for each outcome. The first bias was due to this being a case-controlled study. The sampling fractions caused a bias in the probabilities that were calculated using the models. The second bias is caused by a change in the proportions for each event. If at a later date the proportions (a priori probabilities) of explosions versus earthquakes change, this would cause a bias in the predicted probability for an event. When using logistic regression, the user needs to be aware of the possible biases and what affect they will have on the predicted probabilities.

  2. Least-Squares Linear Regression and Schrodinger's Cat: Perspectives on the Analysis of Regression Residuals.

    ERIC Educational Resources Information Center

    Hecht, Jeffrey B.

    The analysis of regression residuals and detection of outliers are discussed, with emphasis on determining how deviant an individual data point must be to be considered an outlier and the impact that multiple suspected outlier data points have on the process of outlier determination and treatment. Only bivariate (one dependent and one independent)…

  3. Atavistic regression as a factor in the remission of cancer.

    PubMed

    Meares, A

    1977-07-23

    It is suggested that the atavistic regression of the mind in intensive meditation is accompanied by a similar physiological regression, and that this may involve the immune system and so influence the patient's defences against cancer.

  4. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

    PubMed Central

    Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

    2016-01-01

    Objective Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. Material and Methods In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient’s baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. Results The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years [“for the long- and antagonist-protocol groups, respectively”]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Conclusion Our results show that ART cycles could be

  5. A novel approach using a minimal number of injections during the IVF/ICSI cycle: Luteal half-dose depot GnRH agonist following corifollitropin alfa versus the corifollitropin alfa with a GnRH-antagonist cycle

    PubMed Central

    Haydardedeoğlu, Bülent; Kılıçdağ, Esra Bulgan

    2016-01-01

    Objective Corifollitropin alfa is a good choice for assisted reproductive technology (ART) cycles because fewer injections are needed than with other agents. In this retrospective cohort, we analyzed luteal injected half-dose depot gonadotropin hormone-releasing hormone (GnRH) agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist. Material and Methods In this retrospective cohort, we analyzed luteal injected half-dose depot GnRH agonist cycles in women who received corifollitropin alfa and those who underwent a conventional corifollitropin alfa cycle with a GnRH antagonist at the Division of Reproductive Endocrinology and IVF Unit, Obstetrics and Gynecology Department, Başkent University School of Medicine, Adana, Turkey, from March 2014 to August 2015. The patient’s baseline characteristics were similar between the two groups. Forty-five patients underwent the long protocol, in which a half-dose of depot GnRH agonist was administered on day 21 of the preceding cycle. Forty-nine patients underwent the GnRH-antagonist protocol. Corifollitropin alfa was administered on the menstrual cycle day 3. Results The mean ages of the two groups were similar (32.77±5.55 vs. 34.2±4.51 years [“for the long- and antagonist-protocol groups, respectively”]). The total number of retrieved oocytes, the fertilization rate, and the number of transferred embryos were similar between the two groups. The only significant difference between the two protocols was the number of injections during the controlled ovarian stimulation (COH) cycle, which included the depot-agonist injection in the long-protocol group (4.46±1.64 vs. 5.71±2.51, p=0.006). The clinical pregnancy and implantation rates were similar in the two protocols (16/45 [35.6%] vs. 16/49 [32.7%] for the intention to treat and 32.5±6.82% vs. 36.25±8.58%, respectively). Conclusion Our results show that ART cycles could be

  6. IVF/ICSI outcomes between cycles with luteal estradiol (E2) pre-treatment before GnRH antagonist protocol and standard long GnRH agonist protocol: a prospective and randomized study

    PubMed Central

    Huang, Guo-ning; Zeng, Ping-hong; Pei, Li

    2009-01-01

    Objective To study if luteal E2 pre-treatment before GnRH antagonist protocol improves IVF/ICSI outcomes compared with standard long GnRH agonist protocol. Design A prospective, randomized and controlled study. Setting ART center of a state public hospital Patient(s) Two hundred twenty infertile women underwent IVF/ICSI treatments. Intervention(s) Participants received oral Estradiol Valerate 4 mg/day preceding the IVF cycle from day 21 until day 2 of next cycle before GnRH antagonist protocol (E2 pre-treatment group n = 109) or received standard long GnRH agonist protocol as control group (n = 111). Main outcome measure(s) Number of oocytes collected, MII oocytes, fertilization, implantation, live birth and early pregnancy rate, and hormone profiles. Result(s) E2 pre-treatment exerted a significant suppressive effect on FSH but not LH secretion compared with basal FSH and LH levels. In E2 pre-treatment group serum LH level was significantly higher during COH and serum P was also significantly higher on the day of HCG injection compared with control group. Five patients from E2 pre-treatment group had elevated LH at all time (≥10 IU/L) and also a concomitantly high P (>1 ng/mL). Two of the five women achieved pregnancy but had early pregnancy loss. Overall, IVF/ICSI outcomes such as implantation, clinical pregnancy and live birth rates were similar between E2 pre-treatment and control groups. Conclusion(s) Luteal E2 pre-treatment before GnRH antagonist protocol significantly increases serum LH level and incidence rate of premature LH but no significant effect is observed on implantation, clinical pregnancy, live birth and early pregnancy loss rates compared with long GnRH agonist protocol. However, more studies in large numbers of cycles are needed to confirm that increased serum LH level by E2 pre-treatment during COH has no negative effect on the IVF/ICSI outcomes. PMID:19225876

  7. Deep Wavelet Scattering for Quantum Energy Regression

    NASA Astrophysics Data System (ADS)

    Hirn, Matthew

    Physical functionals are usually computed as solutions of variational problems or from solutions of partial differential equations, which may require huge computations for complex systems. Quantum chemistry calculations of ground state molecular energies is such an example. Indeed, if x is a quantum molecular state, then the ground state energy E0 (x) is the minimum eigenvalue solution of the time independent Schrödinger Equation, which is computationally intensive for large systems. Machine learning algorithms do not simulate the physical system but estimate solutions by interpolating values provided by a training set of known examples {(xi ,E0 (xi) } i <= n . However, precise interpolations may require a number of examples that is exponential in the system dimension, and are thus intractable. This curse of dimensionality may be circumvented by computing interpolations in smaller approximation spaces, which take advantage of physical invariants. Linear regressions of E0 over a dictionary Φ ={ϕk } k compute an approximation E 0 as: E 0 (x) =∑kwkϕk (x) , where the weights {wk } k are selected to minimize the error between E0 and E 0 on the training set. The key to such a regression approach then lies in the design of the dictionary Φ. It must be intricate enough to capture the essential variability of E0 (x) over the molecular states x of interest, while simple enough so that evaluation of Φ (x) is significantly less intensive than a direct quantum mechanical computation (or approximation) of E0 (x) . In this talk we present a novel dictionary Φ for the regression of quantum mechanical energies based on the scattering transform of an intermediate, approximate electron density representation ρx of the state x. The scattering transform has the architecture of a deep convolutional network, composed of an alternating sequence of linear filters and nonlinear maps. Whereas in many deep learning tasks the linear filters are learned from the training data, here

  8. Spatial vulnerability assessments by regression kriging

    NASA Astrophysics Data System (ADS)

    Pásztor, László; Laborczi, Annamária; Takács, Katalin; Szatmári, Gábor

    2016-04-01

    information representing IEW or GRP forming environmental factors were taken into account to support the spatial inference of the locally experienced IEW frequency and measured GRP values respectively. An efficient spatial prediction methodology was applied to construct reliable maps, namely regression kriging (RK) using spatially exhaustive auxiliary data on soil, geology, topography, land use and climate. RK divides the spatial inference into two parts. Firstly the deterministic component of the target variable is determined by a regression model. The residuals of the multiple linear regression analysis represent the spatially varying but dependent stochastic component, which are interpolated by kriging. The final map is the sum of the two component predictions. Application of RK also provides the possibility of inherent accuracy assessment. The resulting maps are characterized by global and local measures of its accuracy. Additionally the method enables interval estimation for spatial extension of the areas of predefined risk categories. All of these outputs provide useful contribution to spatial planning, action planning and decision making. Acknowledgement: Our work was partly supported by the Hungarian National Scientific Research Foundation (OTKA, Grant No. K105167).

  9. A new form of bivariate generalized Poisson regression model

    NASA Astrophysics Data System (ADS)

    Faroughi, Pouya; Ismail, Noriszura

    2014-09-01

    This paper introduces a new form of bivariate generalized Poisson (BGP) regression which can be fitted to bivariate and correlated count data with covariates. The BGP regression suggested in this study can be fitted not only to bivariate count data with positive, zero or negative correlations, but also to underdispersed or overdispersed bivariate count data. Applications of bivariate Poisson (BP) regression and the new BGP regression are illustrated on Malaysian motor insurance data.

  10. Logistic Regression: Going beyond Point-and-Click.

    ERIC Educational Resources Information Center

    King, Jason E.

    A review of the literature reveals that important statistical algorithms and indices pertaining to logistic regression are being underused. This paper describes logistic regression in comparison with discriminant analysis and linear regression, and suggests that some techniques only accessible through computer syntax should be consulted in…

  11. Using Time-Series Regression to Predict Academic Library Circulations.

    ERIC Educational Resources Information Center

    Brooks, Terrence A.

    1984-01-01

    Four methods were used to forecast monthly circulation totals in 15 midwestern academic libraries: dummy time-series regression, lagged time-series regression, simple average (straight-line forecasting), monthly average (naive forecasting). In tests of forecasting accuracy, dummy regression method and monthly mean method exhibited smallest average…

  12. Using Leverage and Influence to Introduce Regression Diagnostics.

    ERIC Educational Resources Information Center

    Hoaglin, David C.

    1988-01-01

    Techniques for teaching linear regression are provided. Discussed are leverage and the hat matrix in simple regression, residuals, the notion of leaving out each observation individually, and use of this to study influence on fitted values and to define residuals. Finally, corresponding diagnostics for multiple regression are discussed. (MNS)

  13. Applications of statistics to medical science, III. Correlation and regression.

    PubMed

    Watanabe, Hiroshi

    2012-01-01

    In this third part of a series surveying medical statistics, the concepts of correlation and regression are reviewed. In particular, methods of linear regression and logistic regression are discussed. Arguments related to survival analysis will be made in a subsequent paper.

  14. Testing Different Model Building Procedures Using Multiple Regression.

    ERIC Educational Resources Information Center

    Thayer, Jerome D.

    The stepwise regression method of selecting predictors for computer assisted multiple regression analysis was compared with forward, backward, and best subsets regression, using 16 data sets. The results indicated the stepwise method was preferred because of its practical nature, when the models chosen by different selection methods were similar…

  15. Relationship between Multiple Regression and Selected Multivariable Methods.

    ERIC Educational Resources Information Center

    Schumacker, Randall E.

    The relationship of multiple linear regression to various multivariate statistical techniques is discussed. The importance of the standardized partial regression coefficient (beta weight) in multiple linear regression as it is applied in path, factor, LISREL, and discriminant analyses is emphasized. The multivariate methods discussed in this paper…

  16. Using Dominance Analysis to Determine Predictor Importance in Logistic Regression

    ERIC Educational Resources Information Center

    Azen, Razia; Traxel, Nicole

    2009-01-01

    This article proposes an extension of dominance analysis that allows researchers to determine the relative importance of predictors in logistic regression models. Criteria for choosing logistic regression R[superscript 2] analogues were determined and measures were selected that can be used to perform dominance analysis in logistic regression. A…

  17. Father regression. Clinical narratives and theoretical reflections.

    PubMed

    Stein, Ruth

    2006-08-01

    The author deals with love-hate enthrallment and submission to a primitive paternal object. This is a father-son relationship that extends through increasing degrees of 'primitiveness' or extremeness, and is illustrated through three different constellations that constitute a continuum. One pole of the continuum encompasses certain male patients who show a loving, de-individuated connection to a father experienced as trustworthy, soft, and in need of protection. Further along the continuum is the case of a transsexual patient whose analysis revealed an intense 'God-transference', a bondage to an idealized, feared, and ostensibly protective father-God introject. A great part of this patient's analysis consisted in a fierce struggle to liberate himself from this figure. The other end of the continuum is occupied by religious terrorists, who exemplify the most radical thralldom to a persecutory, godly object, a regressive submission that banishes woman and enthrones a cruel superego, and that ends in destruction and self-destruction. Psychoanalytic thinking has traditionally dealt with the oedipal father and recently with the nurturing father, but there is a gap in thinking about the phallic, archaic father, and his relations with his son(s). The author aims at filling this gap, at the same time as she also raises the very question of 'What is a father?' linking it with literary and religious themes. PMID:16877249

  18. Sparse Regression as a Sparse Eigenvalue Problem

    NASA Technical Reports Server (NTRS)

    Moghaddam, Baback; Gruber, Amit; Weiss, Yair; Avidan, Shai

    2008-01-01

    We extend the l0-norm "subspectral" algorithms for sparse-LDA [5] and sparse-PCA [6] to general quadratic costs such as MSE in linear (kernel) regression. The resulting "Sparse Least Squares" (SLS) problem is also NP-hard, by way of its equivalence to a rank-1 sparse eigenvalue problem (e.g., binary sparse-LDA [7]). Specifically, for a general quadratic cost we use a highly-efficient technique for direct eigenvalue computation using partitioned matrix inverses which leads to dramatic x103 speed-ups over standard eigenvalue decomposition. This increased efficiency mitigates the O(n4) scaling behaviour that up to now has limited the previous algorithms' utility for high-dimensional learning problems. Moreover, the new computation prioritizes the role of the less-myopic backward elimination stage which becomes more efficient than forward selection. Similarly, branch-and-bound search for Exact Sparse Least Squares (ESLS) also benefits from partitioned matrix inverse techniques. Our Greedy Sparse Least Squares (GSLS) generalizes Natarajan's algorithm [9] also known as Order-Recursive Matching Pursuit (ORMP). Specifically, the forward half of GSLS is exactly equivalent to ORMP but more efficient. By including the backward pass, which only doubles the computation, we can achieve lower MSE than ORMP. Experimental comparisons to the state-of-the-art LARS algorithm [3] show forward-GSLS is faster, more accurate and more flexible in terms of choice of regularization

  19. Flexible regression models over river networks

    PubMed Central

    O’Donnell, David; Rushworth, Alastair; Bowman, Adrian W; Marian Scott, E; Hallard, Mark

    2014-01-01

    Many statistical models are available for spatial data but the vast majority of these assume that spatial separation can be measured by Euclidean distance. Data which are collected over river networks constitute a notable and commonly occurring exception, where distance must be measured along complex paths and, in addition, account must be taken of the relative flows of water into and out of confluences. Suitable models for this type of data have been constructed based on covariance functions. The aim of the paper is to place the focus on underlying spatial trends by adopting a regression formulation and using methods which allow smooth but flexible patterns. Specifically, kernel methods and penalized splines are investigated, with the latter proving more suitable from both computational and modelling perspectives. In addition to their use in a purely spatial setting, penalized splines also offer a convenient route to the construction of spatiotemporal models, where data are available over time as well as over space. Models which include main effects and spatiotemporal interactions, as well as seasonal terms and interactions, are constructed for data on nitrate pollution in the River Tweed. The results give valuable insight into the changes in water quality in both space and time. PMID:25653460

  20. A rotor optimization using regression analysis

    NASA Technical Reports Server (NTRS)

    Giansante, N.

    1984-01-01

    The design and development of helicopter rotors is subject to the many design variables and their interactions that effect rotor operation. Until recently, selection of rotor design variables to achieve specified rotor operational qualities has been a costly, time consuming, repetitive task. For the past several years, Kaman Aerospace Corporation has successfully applied multiple linear regression analysis, coupled with optimization and sensitivity procedures, in the analytical design of rotor systems. It is concluded that approximating equations can be developed rapidly for a multiplicity of objective and constraint functions and optimizations can be performed in a rapid and cost effective manner; the number and/or range of design variables can be increased by expanding the data base and developing approximating functions to reflect the expanded design space; the order of the approximating equations can be expanded easily to improve correlation between analyzer results and the approximating equations; gradients of the approximating equations can be calculated easily and these gradients are smooth functions reducing the risk of numerical problems in the optimization; the use of approximating functions allows the problem to be started easily and rapidly from various initial designs to enhance the probability of finding a global optimum; and the approximating equations are independent of the analysis or optimization codes used.

  1. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming

    PubMed Central

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S.; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I.; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T.; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R.; Wright, Samuel D.; Espevik, Terje; Schultze, Joachim L.; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

    2016-01-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol levels. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Since cholesterol accumulation and deposition of cholesterol crystals (CCs) triggers a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility, in preventing and reversing atherosclerosis. Here we show that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load, and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques, and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the anti-atherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Since CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

  2. Cyclodextrin promotes atherosclerosis regression via macrophage reprogramming.

    PubMed

    Zimmer, Sebastian; Grebe, Alena; Bakke, Siril S; Bode, Niklas; Halvorsen, Bente; Ulas, Thomas; Skjelland, Mona; De Nardo, Dominic; Labzin, Larisa I; Kerksiek, Anja; Hempel, Chris; Heneka, Michael T; Hawxhurst, Victoria; Fitzgerald, Michael L; Trebicka, Jonel; Björkhem, Ingemar; Gustafsson, Jan-Åke; Westerterp, Marit; Tall, Alan R; Wright, Samuel D; Espevik, Terje; Schultze, Joachim L; Nickenig, Georg; Lütjohann, Dieter; Latz, Eicke

    2016-04-01

    Atherosclerosis is an inflammatory disease linked to elevated blood cholesterol concentrations. Despite ongoing advances in the prevention and treatment of atherosclerosis, cardiovascular disease remains the leading cause of death worldwide. Continuous retention of apolipoprotein B-containing lipoproteins in the subendothelial space causes a local overabundance of free cholesterol. Because cholesterol accumulation and deposition of cholesterol crystals (CCs) trigger a complex inflammatory response, we tested the efficacy of the cyclic oligosaccharide 2-hydroxypropyl-β-cyclodextrin (CD), a compound that increases cholesterol solubility in preventing and reversing atherosclerosis. We showed that CD treatment of murine atherosclerosis reduced atherosclerotic plaque size and CC load and promoted plaque regression even with a continued cholesterol-rich diet. Mechanistically, CD increased oxysterol production in both macrophages and human atherosclerotic plaques and promoted liver X receptor (LXR)-mediated transcriptional reprogramming to improve cholesterol efflux and exert anti-inflammatory effects. In vivo, this CD-mediated LXR agonism was required for the antiatherosclerotic and anti-inflammatory effects of CD as well as for augmented reverse cholesterol transport. Because CD treatment in humans is safe and CD beneficially affects key mechanisms of atherogenesis, it may therefore be used clinically to prevent or treat human atherosclerosis. PMID:27053774

  3. Sliced Inverse Regression for Time Series Analysis

    NASA Astrophysics Data System (ADS)

    Chen, Li-Sue

    1995-11-01

    In this thesis, general nonlinear models for time series data are considered. A basic form is x _{t} = f(beta_sp{1} {T}X_{t-1},beta_sp {2}{T}X_{t-1},... , beta_sp{k}{T}X_ {t-1},varepsilon_{t}), where x_{t} is an observed time series data, X_{t } is the first d time lag vector, (x _{t},x_{t-1},... ,x _{t-d-1}), f is an unknown function, beta_{i}'s are unknown vectors, varepsilon_{t }'s are independent distributed. Special cases include AR and TAR models. We investigate the feasibility applying SIR/PHD (Li 1990, 1991) (the sliced inverse regression and principal Hessian methods) in estimating beta _{i}'s. PCA (Principal component analysis) is brought in to check one critical condition for SIR/PHD. Through simulation and a study on 3 well -known data sets of Canadian lynx, U.S. unemployment rate and sunspot numbers, we demonstrate how SIR/PHD can effectively retrieve the interesting low-dimension structures for time series data.

  4. Rank-preserving regression: a more robust rank regression model against outliers.

    PubMed

    Chen, Tian; Kowalski, Jeanne; Chen, Rui; Wu, Pan; Zhang, Hui; Feng, Changyong; Tu, Xin M

    2016-08-30

    Mean-based semi-parametric regression models such as the popular generalized estimating equations are widely used to improve robustness of inference over parametric models. Unfortunately, such models are quite sensitive to outlying observations. The Wilcoxon-score-based rank regression (RR) provides more robust estimates over generalized estimating equations against outliers. However, the RR and its extensions do not sufficiently address missing data arising in longitudinal studies. In this paper, we propose a new approach to address outliers under a different framework based on the functional response models. This functional-response-model-based alternative not only addresses limitations of the RR and its extensions for longitudinal data, but, with its rank-preserving property, even provides more robust estimates than these alternatives. The proposed approach is illustrated with both real and simulated data. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26934999

  5. Rank-preserving regression: a more robust rank regression model against outliers.

    PubMed

    Chen, Tian; Kowalski, Jeanne; Chen, Rui; Wu, Pan; Zhang, Hui; Feng, Changyong; Tu, Xin M

    2016-08-30

    Mean-based semi-parametric regression models such as the popular generalized estimating equations are widely used to improve robustness of inference over parametric models. Unfortunately, such models are quite sensitive to outlying observations. The Wilcoxon-score-based rank regression (RR) provides more robust estimates over generalized estimating equations against outliers. However, the RR and its extensions do not sufficiently address missing data arising in longitudinal studies. In this paper, we propose a new approach to address outliers under a different framework based on the functional response models. This functional-response-model-based alternative not only addresses limitations of the RR and its extensions for longitudinal data, but, with its rank-preserving property, even provides more robust estimates than these alternatives. The proposed approach is illustrated with both real and simulated data. Copyright © 2016 John Wiley & Sons, Ltd.

  6. [Spatial interpolation of soil organic matter using regression Kriging and geographically weighted regression Kriging].

    PubMed

    Yang, Shun-hua; Zhang, Hai-tao; Guo, Long; Ren, Yan

    2015-06-01

    Relative elevation and stream power index were selected as auxiliary variables based on correlation analysis for mapping soil organic matter. Geographically weighted regression Kriging (GWRK) and regression Kriging (RK) were used for spatial interpolation of soil organic matter and compared with ordinary Kriging (OK), which acts as a control. The results indicated that soil or- ganic matter was significantly positively correlated with relative elevation whilst it had a significantly negative correlation with stream power index. Semivariance analysis showed that both soil organic matter content and its residuals (including ordinary least square regression residual and GWR resi- dual) had strong spatial autocorrelation. Interpolation accuracies by different methods were esti- mated based on a data set of 98 validation samples. Results showed that the mean error (ME), mean absolute error (MAE) and root mean square error (RMSE) of RK were respectively 39.2%, 17.7% and 20.6% lower than the corresponding values of OK, with a relative-improvement (RI) of 20.63. GWRK showed a similar tendency, having its ME, MAE and RMSE to be respectively 60.6%, 23.7% and 27.6% lower than those of OK, with a RI of 59.79. Therefore, both RK and GWRK significantly improved the accuracy of OK interpolation of soil organic matter due to their in- corporation of auxiliary variables. In addition, GWRK performed obviously better than RK did in this study, and its improved performance should be attributed to the consideration of sample spatial locations. PMID:26572015

  7. Regional flood frequency analysis using spatial proximity and basin characteristics: Quantile regression vs. parameter regression technique

    NASA Astrophysics Data System (ADS)

    Ahn, Kuk-Hyun; Palmer, Richard

    2016-09-01

    Despite wide use of regression-based regional flood frequency analysis (RFFA) methods, the majority are based on either ordinary least squares (OLS) or generalized least squares (GLS). This paper proposes 'spatial proximity' based RFFA methods using the spatial lagged model (SLM) and spatial error model (SEM). The proposed methods are represented by two frameworks: the quantile regression technique (QRT) and parameter regression technique (PRT). The QRT develops prediction equations for flooding quantiles in average recurrence intervals (ARIs) of 2, 5, 10, 20, and 100 years whereas the PRT provides prediction of three parameters for the selected distribution. The proposed methods are tested using data incorporating 30 basin characteristics from 237 basins in Northeastern United States. Results show that generalized extreme value (GEV) distribution properly represents flood frequencies in the study gages. Also, basin area, stream network, and precipitation seasonality are found to be the most effective explanatory variables in prediction modeling by the QRT and PRT. 'Spatial proximity' based RFFA methods provide reliable flood quantile estimates compared to simpler methods. Compared to the QRT, the PRT may be recommended due to its accuracy and computational simplicity. The results presented in this paper may serve as one possible guidepost for hydrologists interested in flood analysis at ungaged sites.

  8. Effect of a single intrauterine administration of recombinant bovine interferon-τ on day 7 of the estrous cycle on the luteal phase length and blood profile in dairy cows.

    PubMed

    Matsunaga, S; Osawa, T; Geshi, M; Takahashi, H; Inumaru, S; Yokomizo, Y; Miyake, Y-I

    2012-08-01

    This study tested the effect of recombinant bovine interferon-tau (rboIFN-τ) on the length of estrous cycle, luteal lifespan and side effects of rboIFN-τ in the cow. A normal estrous cycle in six non-lactating cycling Holstein cows was observed (non-treated cycle), and either 2.0 mg of liposomalized rboIFN-τ (treated cycle) or bovine serum albumin (BSA; placebo cycle) was infused in the uterus on day 7 of the estrous cycle (day 0=day of ovulation). Rectal temperature, heart rate and respiratory rate were recorded and blood samples were collected before and after the treatments. The length of the estrous cycle and corpus luteum lifespan in rboIFN-τ treated cycles were not significantly different from those of the non-treated and placebo cycles. In contrast, the rboIFN-τ treatment caused a transient increase in rectal temperature and a decrease in the number of peripheral lymphocytes and neutrophils after the treatment.

  9. Down-regulation of stromal cell-derived factor-1alpha-induced T cell chemotaxis by a peptide based on the complementarity-determining region 1 of an anti-DNA autoantibody via up-regulation of TGF-beta secretion.

    PubMed

    Sela, Uri; Hershkoviz, Rami; Cahalon, Liora; Lider, Ofer; Mozes, Edna

    2005-01-01

    Systemic lupus erythematosus (SLE) can be induced in mice by immunizing them with a monoclonal human anti-DNA Ab that expresses a major Id, designated 16/6Id. In addition, a peptide based on the sequence of the CDR 1 (hCDR1) of the 16/6Id ameliorated the clinical manifestations of SLE in experimental models. In this study we examined the effects of treating mice with human complementary-determining region 1 (hCDR1) on the subsequent chemotaxis of T cells derived from 16/6Id-primed mice. First we demonstrated elevated levels of stromal cell-derived factor-1alpha (SDF-1alpha) in the sera of SLE-afflicted mice and in the sera and lymphoid tissues of 16/6Id-immunized BALB/c mice shortly after the immunization. We then found that administration of hCDR1 to 16/6Id-immunized mice specifically down-regulated SDF1alpha-induced T cell chemotaxis through fibronectin and collagen type I. This was accompanied by diminished SDF1-alpha-induced T cell adhesion and ERK phosphorylation. Treatment with hCDR1 up-regulated TGF-beta secretion, which, in turn, inhibited the murine T cell adhesion to and chemotaxis through fibronectin as well as their ERK phosphorylation. Thus, the secretion of TGF-beta after treatment of 16/6Id-immunized mice with hCDR1 plays an important role in the down-regulation of SDF-1alpha-mediated T cell activation and the interactions with extracellular matrix moieties observed in the present study. PMID:15611253

  10. Sirenomelia and severe caudal regression syndrome

    PubMed Central

    Seidahmed, Mohammed Z.; Abdelbasit, Omer B.; Alhussein, Khalid A.; Miqdad, Abeer M.; Khalil, Mohammed I.; Salih, Mustafa A.

    2014-01-01

    Objective: To describe cases of sirenomelia and severe caudal regression syndrome (CRS), to report the prevalence of sirenomelia, and compare our findings with the literature. Methods: Retrospective data was retrieved from the medical records of infants with the diagnosis of sirenomelia and CRS and their mothers from 1989 to 2010 (22 years) at the Security Forces Hospital, Riyadh, Saudi Arabia. A perinatologist, neonatologist, pediatric neurologist, and radiologist ascertained the diagnoses. The cases were identified as part of a study of neural tube defects during that period. A literature search was conducted using MEDLINE. Results: During the 22-year study period, the total number of deliveries was 124,933 out of whom, 4 patients with sirenomelia, and 2 patients with severe forms of CRS were identified. All the patients with sirenomelia had single umbilical artery, and none were the infant of a diabetic mother. One patient was a twin, and another was one of triplets. The 2 patients with CRS were sisters, their mother suffered from type II diabetes mellitus and morbid obesity on insulin, and neither of them had a single umbilical artery. Other associated anomalies with sirenomelia included an absent radius, thumb, and index finger in one patient, Potter’s syndrome, abnormal ribs, microphthalmia, congenital heart disease, hypoplastic lungs, and diaphragmatic hernia. Conclusion: The prevalence of sirenomelia (3.2 per 100,000) is high compared with the international prevalence of one per 100,000. Both cases of CRS were infants of type II diabetic mother with poor control, supporting the strong correlation of CRS and maternal diabetes. PMID:25551110

  11. Deep Human Parsing with Active Template Regression.

    PubMed

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28]. PMID:26539846

  12. Deep Human Parsing with Active Template Regression.

    PubMed

    Liang, Xiaodan; Liu, Si; Shen, Xiaohui; Yang, Jianchao; Liu, Luoqi; Dong, Jian; Lin, Liang; Yan, Shuicheng

    2015-12-01

    In this work, the human parsing task, namely decomposing a human image into semantic fashion/body regions, is formulated as an active template regression (ATR) problem, where the normalized mask of each fashion/body item is expressed as the linear combination of the learned mask templates, and then morphed to a more precise mask with the active shape parameters, including position, scale and visibility of each semantic region. The mask template coefficients and the active shape parameters together can generate the human parsing results, and are thus called the structure outputs for human parsing. The deep Convolutional Neural Network (CNN) is utilized to build the end-to-end relation between the input human image and the structure outputs for human parsing. More specifically, the structure outputs are predicted by two separate networks. The first CNN network is with max-pooling, and designed to predict the template coefficients for each label mask, while the second CNN network is without max-pooling to preserve sensitivity to label mask position and accurately predict the active shape parameters. For a new image, the structure outputs of the two networks are fused to generate the probability of each label for each pixel, and super-pixel smoothing is finally used to refine the human parsing result. Comprehensive evaluations on a large dataset well demonstrate the significant superiority of the ATR framework over other state-of-the-arts for human parsing. In particular, the F1-score reaches 64.38 percent by our ATR framework, significantly higher than 44.76 percent based on the state-of-the-art algorithm [28].

  13. Kepler AutoRegressive Planet Search

    NASA Astrophysics Data System (ADS)

    Caceres, Gabriel Antonio; Feigelson, Eric

    2016-01-01

    The Kepler AutoRegressive Planet Search (KARPS) project uses statistical methodology associated with autoregressive (AR) processes to model Kepler lightcurves in order to improve exoplanet transit detection in systems with high stellar variability. We also introduce a planet-search algorithm to detect transits in time-series residuals after application of the AR models. One of the main obstacles in detecting faint planetary transits is the intrinsic stellar variability of the host star. The variability displayed by many stars may have autoregressive properties, wherein later flux values are correlated with previous ones in some manner. Our analysis procedure consisting of three steps: pre-processing of the data to remove discontinuities, gaps and outliers; AR-type model selection and fitting; and transit signal search of the residuals using a new Transit Comb Filter (TCF) that replaces traditional box-finding algorithms. The analysis procedures of the project are applied to a portion of the publicly available Kepler light curve data for the full 4-year mission duration. Tests of the methods have been made on a subset of Kepler Objects of Interest (KOI) systems, classified both as planetary `candidates' and `false positives' by the Kepler Team, as well as a random sample of unclassified systems. We find that the ARMA-type modeling successfully reduces the stellar variability, by a factor of 10 or more in active stars and by smaller factors in more quiescent stars. A typical quiescent Kepler star has an interquartile range (IQR) of ~10 e-/sec, which may improve slightly after modeling, while those with IQR ranging from 20 to 50 e-/sec, have improvements from 20% up to 70%. High activity stars (IQR exceeding 100) markedly improve. A periodogram based on the TCF is constructed to concentrate the signal of these periodic spikes. When a periodic transit is found, the model is displayed on a standard period-folded averaged light curve. Our findings to date on real

  14. Enhancement of Visual Field Predictions with Pointwise Exponential Regression (PER) and Pointwise Linear Regression (PLR)

    PubMed Central

    Morales, Esteban; de Leon, John Mark S.; Abdollahi, Niloufar; Yu, Fei; Nouri-Mahdavi, Kouros; Caprioli, Joseph

    2016-01-01

    Purpose The study was conducted to evaluate threshold smoothing algorithms to enhance prediction of the rates of visual field (VF) worsening in glaucoma. Methods We studied 798 patients with primary open-angle glaucoma and 6 or more years of follow-up who underwent 8 or more VF examinations. Thresholds at each VF location for the first 4 years or first half of the follow-up time (whichever was greater) were smoothed with clusters defined by the nearest neighbor (NN), Garway-Heath, Glaucoma Hemifield Test (GHT), and weighting by the correlation of rates at all other VF locations. Thresholds were regressed with a pointwise exponential regression (PER) model and a pointwise linear regression (PLR) model. Smaller root mean square error (RMSE) values of the differences between the observed and the predicted thresholds at last two follow-ups indicated better model predictions. Results The mean (SD) follow-up times for the smoothing and prediction phase were 5.3 (1.5) and 10.5 (3.9) years. The mean RMSE values for the PER and PLR models were unsmoothed data, 6.09 and 6.55; NN, 3.40 and 3.42; Garway-Heath, 3.47 and 3.48; GHT, 3.57 and 3.74; and correlation of rates, 3.59 and 3.64. Conclusions Smoothed VF data predicted better than unsmoothed data. Nearest neighbor provided the best predictions; PER also predicted consistently more accurately than PLR. Smoothing algorithms should be used when forecasting VF results with PER or PLR. Translational Relevance The application of smoothing algorithms on VF data can improve forecasting in VF points to assist in treatment decisions. PMID:26998405

  15. Local Linear Regression for Data with AR Errors

    PubMed Central

    Li, Runze; Li, Yan

    2009-01-01

    In many statistical applications, data are collected over time, and they are likely correlated. In this paper, we investigate how to incorporate the correlation information into the local linear regression. Under the assumption that the error process is an auto-regressive process, a new estimation procedure is proposed for the nonparametric regression by using local linear regression method and the profile least squares techniques. We further propose the SCAD penalized profile least squares method to determine the order of auto-regressive process. Extensive Monte Carlo simulation studies are conducted to examine the finite sample performance of the proposed procedure, and to compare the performance of the proposed procedures with the existing one. From our empirical studies, the newly proposed procedures can dramatically improve the accuracy of naive local linear regression with working-independent error structure. We illustrate the proposed methodology by an analysis of real data set. PMID:20161374

  16. Estimating peak flow characteristics at ungaged sites by ridge regression

    USGS Publications Warehouse

    Tasker, Gary D.

    1982-01-01

    A regression simulation model, is combined with a multisite streamflow generator to simulate a regional regression of 50-year peak discharge against a set of basin characteristics. Monte Carlo experiments are used to compare the unbiased ordinary lease squares parameter estimator with Hoerl and Kennard's (1970a) ridge estimator in which the biasing parameter is that proposed by Hoerl, Kennard, and Baldwin (1975). The simulation results indicate a substantial improvement in parameter estimation using ridge regression when the correlation between basin characteristics is more than about 0.90. In addition, results indicate a strong potential for improving the mean square error of prediction of a peak-flow characteristic versus basin characteristics regression model when the basin characteristics are approximately colinear. The simulation covers a range of regression parameters, streamflow statistics, and basin characteristics commonly found in regional regression studies.

  17. Algorithm For Solution Of Subset-Regression Problems

    NASA Technical Reports Server (NTRS)

    Verhaegen, Michel

    1991-01-01

    Reliable and flexible algorithm for solution of subset-regression problem performs QR decomposition with new column-pivoting strategy, enables selection of subset directly from originally defined regression parameters. This feature, in combination with number of extensions, makes algorithm very flexible for use in analysis of subset-regression problems in which parameters have physical meanings. Also extended to enable joint processing of columns contaminated by noise with those free of noise, without using scaling techniques.

  18. Neighborhood social capital and crime victimization: comparison of spatial regression analysis and hierarchical regression analysis.

    PubMed

    Takagi, Daisuke; Ikeda, Ken'ichi; Kawachi, Ichiro

    2012-11-01

    Crime is an important determinant of public health outcomes, including quality of life, mental well-being, and health behavior. A body of research has documented the association between community social capital and crime victimization. The association between social capital and crime victimization has been examined at multiple levels of spatial aggregation, ranging from entire countries, to states, metropolitan areas, counties, and neighborhoods. In multilevel analysis, the spatial boundaries at level 2 are most often drawn from administrative boundaries (e.g., Census tracts in the U.S.). One problem with adopting administrative definitions of neighborhoods is that it ignores spatial spillover. We conducted a study of social capital and crime victimization in one ward of Tokyo city, using a spatial Durbin model with an inverse-distance weighting matrix that assigned each respondent a unique level of "exposure" to social capital based on all other residents' perceptions. The study is based on a postal questionnaire sent to 20-69 years old residents of Arakawa Ward, Tokyo. The response rate was 43.7%. We examined the contextual influence of generalized trust, perceptions of reciprocity, two types of social network variables, as well as two principal components of social capital (constructed from the above four variables). Our outcome measure was self-reported crime victimization in the last five years. In the spatial Durbin model, we found that neighborhood generalized trust, reciprocity, supportive networks and two principal components of social capital were each inversely associated with crime victimization. By contrast, a multilevel regression performed with the same data (using administrative neighborhood boundaries) found generally null associations between neighborhood social capital and crime. Spatial regression methods may be more appropriate for investigating the contextual influence of social capital in homogeneous cultural settings such as Japan.

  19. Contrasting OLS and Quantile Regression Approaches to Student "Growth" Percentiles

    ERIC Educational Resources Information Center

    Castellano, Katherine Elizabeth; Ho, Andrew Dean

    2013-01-01

    Regression methods can locate student test scores in a conditional distribution, given past scores. This article contrasts and clarifies two approaches to describing these locations in terms of readily interpretable percentile ranks or "conditional status percentile ranks." The first is Betebenner's quantile regression approach that results in…

  20. Cautionary Remarks on the Use of Clusterwise Regression

    ERIC Educational Resources Information Center

    Brusco, Michael J.; Cradit, J. Dennis; Steinley, Douglas; Fox, Gavin L.

    2008-01-01

    Clusterwise linear regression is a multivariate statistical procedure that attempts to cluster objects with the objective of minimizing the sum of the error sums of squares for the within-cluster regression models. In this article, we show that the minimization of this criterion makes no effort to distinguish the error explained by the…

  1. An Importance Sampling EM Algorithm for Latent Regression Models

    ERIC Educational Resources Information Center

    von Davier, Matthias; Sinharay, Sandip

    2007-01-01

    Reporting methods used in large-scale assessments such as the National Assessment of Educational Progress (NAEP) rely on latent regression models. To fit the latent regression model using the maximum likelihood estimation technique, multivariate integrals must be evaluated. In the computer program MGROUP used by the Educational Testing Service for…

  2. A Regression Equation for Determining the Dimensionality of Data.

    ERIC Educational Resources Information Center

    Keeling, Kellie B.

    2000-01-01

    Developed a new regression equation to estimate the mean value of eigenvalues in parallel analysis and studied the performance of the equation in comparison with previously published regression equations through simulation. Performance of the new equation was comparable to that of the LCHF equation of G. Lautenschlager and others (1989). (SLD)

  3. Semisupervised Clustering by Iterative Partition and Regression with Neuroscience Applications

    PubMed Central

    Qian, Guoqi; Wu, Yuehua; Ferrari, Davide; Qiao, Puxue; Hollande, Frédéric

    2016-01-01

    Regression clustering is a mixture of unsupervised and supervised statistical learning and data mining method which is found in a wide range of applications including artificial intelligence and neuroscience. It performs unsupervised learning when it clusters the data according to their respective unobserved regression hyperplanes. The method also performs supervised learning when it fits regression hyperplanes to the corresponding data clusters. Applying regression clustering in practice requires means of determining the underlying number of clusters in the data, finding the cluster label of each data point, and estimating the regression coefficients of the model. In this paper, we review the estimation and selection issues in regression clustering with regard to the least squares and robust statistical methods. We also provide a model selection based technique to determine the number of regression clusters underlying the data. We further develop a computing procedure for regression clustering estimation and selection. Finally, simulation studies are presented for assessing the procedure, together with analyzing a real data set on RGB cell marking in neuroscience to illustrate and interpret the method. PMID:27212939

  4. Tutorial on Using Regression Models with Count Outcomes Using R

    ERIC Educational Resources Information Center

    Beaujean, A. Alexander; Morgan, Grant B.

    2016-01-01

    Education researchers often study count variables, such as times a student reached a goal, discipline referrals, and absences. Most researchers that study these variables use typical regression methods (i.e., ordinary least-squares) either with or without transforming the count variables. In either case, using typical regression for count data can…

  5. Stochastic Approximation Methods for Latent Regression Item Response Models

    ERIC Educational Resources Information Center

    von Davier, Matthias; Sinharay, Sandip

    2010-01-01

    This article presents an application of a stochastic approximation expectation maximization (EM) algorithm using a Metropolis-Hastings (MH) sampler to estimate the parameters of an item response latent regression model. Latent regression item response models are extensions of item response theory (IRT) to a latent variable model with covariates…

  6. Augmenting Data with Published Results in Bayesian Linear Regression

    ERIC Educational Resources Information Center

    de Leeuw, Christiaan; Klugkist, Irene

    2012-01-01

    In most research, linear regression analyses are performed without taking into account published results (i.e., reported summary statistics) of similar previous studies. Although the prior density in Bayesian linear regression could accommodate such prior knowledge, formal models for doing so are absent from the literature. The goal of this…

  7. Quantile Regression in the Study of Developmental Sciences

    ERIC Educational Resources Information Center

    Petscher, Yaacov; Logan, Jessica A. R.

    2014-01-01

    Linear regression analysis is one of the most common techniques applied in developmental research, but only allows for an estimate of the average relations between the predictor(s) and the outcome. This study describes quantile regression, which provides estimates of the relations between the predictor(s) and outcome, but across multiple points of…

  8. A Methodology for Generating Placement Rules that Utilizes Logistic Regression

    ERIC Educational Resources Information Center

    Wurtz, Keith

    2008-01-01

    The purpose of this article is to provide the necessary tools for institutional researchers to conduct a logistic regression analysis and interpret the results. Aspects of the logistic regression procedure that are necessary to evaluate models are presented and discussed with an emphasis on cutoff values and choosing the appropriate number of…

  9. An Effect Size for Regression Predictors in Meta-Analysis

    ERIC Educational Resources Information Center

    Aloe, Ariel M.; Becker, Betsy Jane

    2012-01-01

    A new effect size representing the predictive power of an independent variable from a multiple regression model is presented. The index, denoted as r[subscript sp], is the semipartial correlation of the predictor with the outcome of interest. This effect size can be computed when multiple predictor variables are included in the regression model…

  10. Population-Sample Regression in the Estimation of Population Proportions

    ERIC Educational Resources Information Center

    Weitzman, R. A.

    2006-01-01

    Focusing on a single sample obtained randomly with replacement from a single population, this article examines the regression of population on sample proportions and develops an unbiased estimator of the square of the correlation between them. This estimator turns out to be the regression coefficient. Use of the squared-correlation estimator as a…

  11. Interpreting Bivariate Regression Coefficients: Going beyond the Average

    ERIC Educational Resources Information Center

    Halcoussis, Dennis; Phillips, G. Michael

    2010-01-01

    Statistics, econometrics, investment analysis, and data analysis classes often review the calculation of several types of averages, including the arithmetic mean, geometric mean, harmonic mean, and various weighted averages. This note shows how each of these can be computed using a basic regression framework. By recognizing when a regression model…

  12. General Nature of Multicollinearity in Multiple Regression Analysis.

    ERIC Educational Resources Information Center

    Liu, Richard

    1981-01-01

    Discusses multiple regression, a very popular statistical technique in the field of education. One of the basic assumptions in regression analysis requires that independent variables in the equation should not be highly correlated. The problem of multicollinearity and some of the solutions to it are discussed. (Author)

  13. The Precision Efficacy Analysis for Regression Sample Size Method.

    ERIC Educational Resources Information Center

    Brooks, Gordon P.; Barcikowski, Robert S.

    The general purpose of this study was to examine the efficiency of the Precision Efficacy Analysis for Regression (PEAR) method for choosing appropriate sample sizes in regression studies used for precision. The PEAR method, which is based on the algebraic manipulation of an accepted cross-validity formula, essentially uses an effect size to…

  14. A SEMIPARAMETRIC BAYESIAN MODEL FOR CIRCULAR-LINEAR REGRESSION

    EPA Science Inventory

    We present a Bayesian approach to regress a circular variable on a linear predictor. The regression coefficients are assumed to have a nonparametric distribution with a Dirichlet process prior. The semiparametric Bayesian approach gives added flexibility to the model and is usefu...

  15. Floating Data and the Problem with Illustrating Multiple Regression.

    ERIC Educational Resources Information Center

    Sachau, Daniel A.

    2000-01-01

    Discusses how to introduce basic concepts of multiple regression by creating a large-scale, three-dimensional regression model using the classroom walls and floor. Addresses teaching points that should be covered and reveals student reaction to the model. Finds that the greatest benefit of the model is the low fear, walk-through, nonmathematical…

  16. Who Will Win?: Predicting the Presidential Election Using Linear Regression

    ERIC Educational Resources Information Center

    Lamb, John H.

    2007-01-01

    This article outlines a linear regression activity that engages learners, uses technology, and fosters cooperation. Students generated least-squares linear regression equations using TI-83 Plus[TM] graphing calculators, Microsoft[C] Excel, and paper-and-pencil calculations using derived normal equations to predict the 2004 presidential election.…

  17. Using Weighted Least Squares Regression for Obtaining Langmuir Sorption Constants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    One of the most commonly used models for describing phosphorus (P) sorption to soils is the Langmuir model. To obtain model parameters, the Langmuir model is fit to measured sorption data using least squares regression. Least squares regression is based on several assumptions including normally dist...

  18. Regression Commonality Analysis: A Technique for Quantitative Theory Building

    ERIC Educational Resources Information Center

    Nimon, Kim; Reio, Thomas G., Jr.

    2011-01-01

    When it comes to multiple linear regression analysis (MLR), it is common for social and behavioral science researchers to rely predominately on beta weights when evaluating how predictors contribute to a regression model. Presenting an underutilized statistical technique, this article describes how organizational researchers can use commonality…

  19. Construction cost estimation of municipal incinerators by fuzzy linear regression

    SciTech Connect

    Chang, N.B.; Chen, Y.L.; Yang, H.H.

    1996-12-31

    Regression analysis has been widely used in engineering cost estimation. It is recognized that the fuzzy structure in cost estimation is a different type of uncertainty compared to the measurement error in the least-squares regression modeling. Hence, the uncertainties encountered in many events of construction and operating costs estimation and prediction cannot be fully depicted by conventional least-squares regression models. This paper presents a construction cost analysis of municipal incinerators by the techniques of fuzzy linear regression. A thorough investigation of construction costs in the Taiwan Resource Recovery Project was conducted based on design parameters such as design capacity, type of grate system, and the selected air pollution control process. The focus has been placed upon the methodology for dealing with the heterogeneity phenomenon of a set of observations for which regression is evaluated.

  20. Many regression algorithms, one unified model: A review.

    PubMed

    Stulp, Freek; Sigaud, Olivier

    2015-09-01

    Regression is the process of learning relationships between inputs and continuous outputs from example data, which enables predictions for novel inputs. The history of regression is closely related to the history of artificial neural networks since the seminal work of Rosenblatt (1958). The aims of this paper are to provide an overview of many regression algorithms, and to demonstrate how the function representation whose parameters they regress fall into two classes: a weighted sum of basis functions, or a mixture of linear models. Furthermore, we show that the former is a special case of the latter. Our ambition is thus to provide a deep understanding of the relationship between these algorithms, that, despite being derived from very different principles, use a function representation that can be captured within one unified model. Finally, step-by-step derivations of the algorithms from first principles and visualizations of their inner workings allow this article to be used as a tutorial for those new to regression.

  1. Induced regression of bovine papillomas by intralesional immunotherapy.

    PubMed

    Hall, H; Teuscher, C; Urie, P; Boden, B; Robison, R

    1994-12-01

    It has long been assumed that papilloma regression is mediated by immunological mechanisms which are probably cellular in nature. The potentiation of these responses may alter the course of papilloma progression. Certain strains of the bacterium Corynebacterium parvum (Propionibacterium acnes) have been shown to augment cellular immune mechanisms by increasing both macrophage and natural killer cell activity. This study involves the use of naturally occurring bovine papillomas to investigate the immune mechanisms involved in induced papilloma regression. Papillomas were treated by intralesional injection of a C. parvum suspension. Treated papillomas were biopsied at various stages of regression. Tissue samples were subjected to immunohistochemical staining to identify specific infiltrating cells. Results showed that intralesional administration of C. parvum was capable of inducing regression of bovine papillomas in 8-15 weeks. Immunological staining revealed that regression was associated with an increased number of CD8+ and gamma delta+ cells in the dermis, as well as a marked infiltration of neutrophils. PMID:7584507

  2. Using Regression Equations Built from Summary Data in the Psychological Assessment of the Individual Case: Extension to Multiple Regression

    ERIC Educational Resources Information Center

    Crawford, John R.; Garthwaite, Paul H.; Denham, Annie K.; Chelune, Gordon J.

    2012-01-01

    Regression equations have many useful roles in psychological assessment. Moreover, there is a large reservoir of published data that could be used to build regression equations; these equations could then be employed to test a wide variety of hypotheses concerning the functioning of individual cases. This resource is currently underused because…

  3. Comparing Methodologies for Developing an Early Warning System: Classification and Regression Tree Model versus Logistic Regression. REL 2015-077

    ERIC Educational Resources Information Center

    Koon, Sharon; Petscher, Yaacov

    2015-01-01

    The purpose of this report was to explicate the use of logistic regression and classification and regression tree (CART) analysis in the development of early warning systems. It was motivated by state education leaders' interest in maintaining high classification accuracy while simultaneously improving practitioner understanding of the rules…

  4. Shrinkage regression-based methods for microarray missing value imputation

    PubMed Central

    2013-01-01

    Background Missing values commonly occur in the microarray data, which usually contain more than 5% missing values with up to 90% of genes affected. Inaccurate missing value estimation results in reducing the power of downstream microarray data analyses. Many types of methods have been developed to estimate missing values. Among them, the regression-based methods are very popular and have been shown to perform better than the other types of methods in many testing microarray datasets. Results To further improve the performances of the regression-based methods, we propose shrinkage regression-based methods. Our methods take the advantage of the correlation structure in the microarray data and select similar genes for the target gene by Pearson correlation coefficients. Besides, our methods incorporate the least squares principle, utilize a shrinkage estimation approach to adjust the coefficients of the regression model, and then use the new coefficients to estimate missing values. Simulation results show that the proposed methods provide more accurate missing value estimation in six testing microarray datasets than the existing regression-based methods do. Conclusions Imputation of missing values is a very important aspect of microarray data analyses because most of the downstream analyses require a complete dataset. Therefore, exploring accurate and efficient methods for estimating missing values has become an essential issue. Since our proposed shrinkage regression-based methods can provide accurate missing value estimation, they are competitive alternatives to the existing regression-based methods. PMID:24565159

  5. Calculation of Solar Radiation by Using Regression Methods

    NASA Astrophysics Data System (ADS)

    Kızıltan, Ö.; Şahin, M.

    2016-04-01

    In this study, solar radiation was estimated at 53 location over Turkey with varying climatic conditions using the Linear, Ridge, Lasso, Smoother, Partial least, KNN and Gaussian process regression methods. The data of 2002 and 2003 years were used to obtain regression coefficients of relevant methods. The coefficients were obtained based on the input parameters. Input parameters were month, altitude, latitude, longitude and landsurface temperature (LST).The values for LST were obtained from the data of the National Oceanic and Atmospheric Administration Advanced Very High Resolution Radiometer (NOAA-AVHRR) satellite. Solar radiation was calculated using obtained coefficients in regression methods for 2004 year. The results were compared statistically. The most successful method was Gaussian process regression method. The most unsuccessful method was lasso regression method. While means bias error (MBE) value of Gaussian process regression method was 0,274 MJ/m2, root mean square error (RMSE) value of method was calculated as 2,260 MJ/m2. The correlation coefficient of related method was calculated as 0,941. Statistical results are consistent with the literature. Used the Gaussian process regression method is recommended for other studies.

  6. Initial external validation of REGRESS in public health graduate students.

    PubMed

    Kidwell, Kelley M; Enders, Felicity B

    2014-12-01

    Linear regression is typically taught as a second and potentially last required (bio)statistics course for Public Health and Clinical and Translational Science students. There has been much research on the attitudes of students toward basic biostatistics, but there has not been much assessing students' understanding of critical regression topics. The REGRESS (REsearch on Global Regression Expectations in StatisticS) quiz developed at Mayo Clinic utilizes 27 questions to assess understanding for simple and multiple linear regression. We performed an initial external validation of this tool with 117 University of Michigan public health students. We compare the results of pre- and postcourse quiz scores from the Michigan cohort to scores of Mayo medical students and professional statisticians. University of Michigan students performed higher than Mayo students on the precourse quiz due to previous related coursework, but did not perform as high postcourse indicating the need for course modification. In the Michigan cohort, REGRESS scores improved by a mean (standard deviation) of 4.6 (3.4), p < 0.0001. Our results support the use of the REGRESS quiz as a learning tool for students and an evaluation tool to identify topics for curricular improvement for teachers, while we highlight future directions of research. PMID:25041650

  7. Initial external validation of REGRESS in public health graduate students.

    PubMed

    Kidwell, Kelley M; Enders, Felicity B

    2014-12-01

    Linear regression is typically taught as a second and potentially last required (bio)statistics course for Public Health and Clinical and Translational Science students. There has been much research on the attitudes of students toward basic biostatistics, but there has not been much assessing students' understanding of critical regression topics. The REGRESS (REsearch on Global Regression Expectations in StatisticS) quiz developed at Mayo Clinic utilizes 27 questions to assess understanding for simple and multiple linear regression. We performed an initial external validation of this tool with 117 University of Michigan public health students. We compare the results of pre- and postcourse quiz scores from the Michigan cohort to scores of Mayo medical students and professional statisticians. University of Michigan students performed higher than Mayo students on the precourse quiz due to previous related coursework, but did not perform as high postcourse indicating the need for course modification. In the Michigan cohort, REGRESS scores improved by a mean (standard deviation) of 4.6 (3.4), p < 0.0001. Our results support the use of the REGRESS quiz as a learning tool for students and an evaluation tool to identify topics for curricular improvement for teachers, while we highlight future directions of research.

  8. Impact of multicollinearity on small sample hydrologic regression models

    NASA Astrophysics Data System (ADS)

    Kroll, Charles N.; Song, Peter

    2013-06-01

    Often hydrologic regression models are developed with ordinary least squares (OLS) procedures. The use of OLS with highly correlated explanatory variables produces multicollinearity, which creates highly sensitive parameter estimators with inflated variances and improper model selection. It is not clear how to best address multicollinearity in hydrologic regression models. Here a Monte Carlo simulation is developed to compare four techniques to address multicollinearity: OLS, OLS with variance inflation factor screening (VIF), principal component regression (PCR), and partial least squares regression (PLS). The performance of these four techniques was observed for varying sample sizes, correlation coefficients between the explanatory variables, and model error variances consistent with hydrologic regional regression models. The negative effects of multicollinearity are magnified at smaller sample sizes, higher correlations between the variables, and larger model error variances (smaller R2). The Monte Carlo simulation indicates that if the true model is known, multicollinearity is present, and the estimation and statistical testing of regression parameters are of interest, then PCR or PLS should be employed. If the model is unknown, or if the interest is solely on model predictions, is it recommended that OLS be employed since using more complicated techniques did not produce any improvement in model performance. A leave-one-out cross-validation case study was also performed using low-streamflow data sets from the eastern United States. Results indicate that OLS with stepwise selection generally produces models across study regions with varying levels of multicollinearity that are as good as biased regression techniques such as PCR and PLS.

  9. Background stratified Poisson regression analysis of cohort data

    PubMed Central

    Langholz, Bryan

    2012-01-01

    Background stratified Poisson regression is an approach that has been used in the analysis of data derived from a variety of epidemiologically important studies of radiation-exposed populations, including uranium miners, nuclear industry workers, and atomic bomb survivors. We describe a novel approach to fit Poisson regression models that adjust for a set of covariates through background stratification while directly estimating the radiation-disease association of primary interest. The approach makes use of an expression for the Poisson likelihood that treats the coefficients for stratum-specific indicator variables as ‘nuisance’ variables and avoids the need to explicitly estimate the coefficients for these stratum-specific parameters. Log-linear models, as well as other general relative rate models, are accommodated. This approach is illustrated using data from the Life Span Study of Japanese atomic bomb survivors and data from a study of underground uranium miners. The point estimate and confidence interval obtained from this ‘conditional’ regression approach are identical to the values obtained using unconditional Poisson regression with model terms for each background stratum. Moreover, it is shown that the proposed approach allows estimation of background stratified Poisson regression models of non-standard form, such as models that parameterize latency effects, as well as regression models in which the number of strata is large, thereby overcoming the limitations of previously available statistical software for fitting background stratified Poisson regression models. PMID:22193911

  10. Background stratified Poisson regression analysis of cohort data.

    PubMed

    Richardson, David B; Langholz, Bryan

    2012-03-01

    Background stratified Poisson regression is an approach that has been used in the analysis of data derived from a variety of epidemiologically important studies of radiation-exposed populations, including uranium miners, nuclear industry workers, and atomic bomb survivors. We describe a novel approach to fit Poisson regression models that adjust for a set of covariates through background stratification while directly estimating the radiation-disease association of primary interest. The approach makes use of an expression for the Poisson likelihood that treats the coefficients for stratum-specific indicator variables as 'nuisance' variables and avoids the need to explicitly estimate the coefficients for these stratum-specific parameters. Log-linear models, as well as other general relative rate models, are accommodated. This approach is illustrated using data from the Life Span Study of Japanese atomic bomb survivors and data from a study of underground uranium miners. The point estimate and confidence interval obtained from this 'conditional' regression approach are identical to the values obtained using unconditional Poisson regression with model terms for each background stratum. Moreover, it is shown that the proposed approach allows estimation of background stratified Poisson regression models of non-standard form, such as models that parameterize latency effects, as well as regression models in which the number of strata is large, thereby overcoming the limitations of previously available statistical software for fitting background stratified Poisson regression models. PMID:22193911

  11. The Immune Response to Papillomavirus During Infection Persistence and Regression

    PubMed Central

    Hibma, Merilyn H

    2012-01-01

    Human papillomavirus (HPV) infections cause a significant global health burden, predominantly due to HPV-associated cancers. HPV infects only the epidermal cells of cutaneous and mucosal skin, without penetration into the dermal tissues. Infections may persist for months or years, contributed by an array of viral immune evasion mechanisms. However in the majority of cases immunity-based regression of HPV lesions does eventually occur. The role of the innate immune response to HPV in persistence and regression of HPV infection is not well understood. Although an initial inflammatory infiltrate may contribute to disease regression, sustained inflammation at the HPV-induced lesions, characterized by macrophage and neutrophil infiltration, has been observed in persistence. Pathogen-associated molecular patterns (PAMPs) are important in innate recognition. The double stranded DNA and an L1 and L2 capsid components of the HPV virion are potential PAMPs that can trigger signaling through cellular pattern recognition receptors, including toll-like receptors (TLR). TLR expression is increased in regressing HPV disease but is reduced in persistent lesions, suggesting a role for TLR in HPV regression. With regard to the adaptive immune response, a key indicator of regression in humans is infiltration of the lesion with both CD4 and CD8 T cells. In individuals with persistent lesions, CD8 T cell and immune suppressive regulatory T cells (Tregs) infiltrate the infection site. There is no association between persistence or regression and the presence of serum antibodies to the viral capsid antigens of HPV. There is still much to be learned about the immunological events that trigger regression of HPV disease. Understanding the viral and host factors that influence persistence and regression is important for the development of better immunotherapeutic treatments for HPV-associated disease. PMID:23341859

  12. Preserving Institutional Privacy in Distributed binary Logistic Regression.

    PubMed

    Wu, Yuan; Jiang, Xiaoqian; Ohno-Machado, Lucila

    2012-01-01

    Privacy is becoming a major concern when sharing biomedical data across institutions. Although methods for protecting privacy of individual patients have been proposed, it is not clear how to protect the institutional privacy, which is many times a critical concern of data custodians. Built upon our previous work, Grid Binary LOgistic REgression (GLORE)1, we developed an Institutional Privacy-preserving Distributed binary Logistic Regression model (IPDLR) that considers both individual and institutional privacy for building a logistic regression model in a distributed manner. We tested our method using both simulated and clinical data, showing how it is possible to protect the privacy of individuals and of institutions using a distributed strategy.

  13. Quantiles Regression Approach to Identifying the Determinant of Breastfeeding Duration

    NASA Astrophysics Data System (ADS)

    Mahdiyah; Norsiah Mohamed, Wan; Ibrahim, Kamarulzaman

    In this study, quantiles regression approach is applied to the data of Malaysian Family Life Survey (MFLS), to identify factors which are significantly related to the different conditional quantiles of the breastfeeding duration. It is known that the classical linear regression methods are based on minimizing residual sum of squared, but quantiles regression use a mechanism which are based on the conditional median function and the full range of other conditional quantile functions. Overall, it is found that the period of breastfeeding is significantly related to place of living, religion and total number of children in the family.

  14. Spontaneous Regression and Recurrence of a Tumefactive Perivascular Space

    PubMed Central

    Muttikkal, Thomas Jose Eluvathingal; Raghavan, Prashant

    2014-01-01

    Summary Perivascular spaces can occasionally appear mass-like (tumefactive or giant perivascular space), and can be associated with clinical symptoms. Spontaneous regression of a tumefactive perivascular space is a very rare phenomenon with only two reported cases in the English medical literature. Spontaneous regression of a tumefactive perivascular space along with resolution of clinical symptoms, followed by spontaneous recurrence associated with symptom recurrence is an extremely rare occurrence, which to the best of our knowledge, has not been reported in the medical literature. We describe a case of spontaneous regression of a tumefactive perivascular space, three years after its initial detection, followed by spontaneous recurrence after two years. PMID:24750709

  15. Teaching and hospital production: the use of regression estimates.

    PubMed

    Lehner, L A; Burgess, J F

    1995-01-01

    Medicare's Prospective Payment System pays U.S. teaching hospitals for the indirect costs of medical education based on a regression coefficient in a cost function. In regression studies using health care data, it is common for explanatory variables to be measured imperfectly, yet the potential for measurement error is often ignored. In this paper, U.S. Department of Veterans Affairs data is used to examine issues of health care production estimation and the use of regression estimates like the teaching adjustment factor. The findings show that measurement error and persistent multicollinearity confound attempts to have a large degree of confidence in the precise magnitude of parameter estimates.

  16. Linear regression analysis of survival data with missing censoring indicators.

    PubMed

    Wang, Qihua; Dinse, Gregg E

    2011-04-01

    Linear regression analysis has been studied extensively in a random censorship setting, but typically all of the censoring indicators are assumed to be observed. In this paper, we develop synthetic data methods for estimating regression parameters in a linear model when some censoring indicators are missing. We define estimators based on regression calibration, imputation, and inverse probability weighting techniques, and we prove all three estimators are asymptotically normal. The finite-sample performance of each estimator is evaluated via simulation. We illustrate our methods by assessing the effects of sex and age on the time to non-ambulatory progression for patients in a brain cancer clinical trial. PMID:20559722

  17. Using ridge regression in systematic pointing error corrections

    NASA Technical Reports Server (NTRS)

    Guiar, C. N.

    1988-01-01

    A pointing error model is used in the antenna calibration process. Data from spacecraft or radio star observations are used to determine the parameters in the model. However, the regression variables are not truly independent, displaying a condition known as multicollinearity. Ridge regression, a biased estimation technique, is used to combat the multicollinearity problem. Two data sets pertaining to Voyager 1 spacecraft tracking (days 105 and 106 of 1987) were analyzed using both linear least squares and ridge regression methods. The advantages and limitations of employing the technique are presented. The problem is not yet fully resolved.

  18. [Unconditioned logistic regression and sample size: a bibliographic review].

    PubMed

    Ortega Calvo, Manuel; Cayuela Domínguez, Aurelio

    2002-01-01

    Unconditioned logistic regression is a highly useful risk prediction method in epidemiology. This article reviews the different solutions provided by different authors concerning the interface between the calculation of the sample size and the use of logistics regression. Based on the knowledge of the information initially provided, a review is made of the customized regression and predictive constriction phenomenon, the design of an ordinal exposition with a binary output, the event of interest per variable concept, the indicator variables, the classic Freeman equation, etc. Some skeptical ideas regarding this subject are also included. PMID:12025266

  19. Poor smokers, poor quitters, and cigarette tax regressivity.

    PubMed

    Remler, Dahlia K

    2004-02-01

    The traditional view that excise taxes are regressive has been challenged. I document the history of the term regressive tax, show that traditional definitions have always found cigarette taxes to be regressive, and illustrate the implications of the greater price responsiveness observed among the poor. I explain the different definitions of tax burden: accounting, welfare-based willingness to pay, and welfare-based time inconsistent. Progressivity (equity across income groups) is sensitive to the way in which tax burden is assessed. Analysis of horizontal equity (fairness within a given income group) shows that cigarette taxes heavily burden poor smokers who do not quit, no matter how tax burden is assessed.

  20. Large Unbalanced Credit Scoring Using Lasso-Logistic Regression Ensemble

    PubMed Central

    Wang, Hong; Xu, Qingsong; Zhou, Lifeng

    2015-01-01

    Recently, various ensemble learning methods with different base classifiers have been proposed for credit scoring problems. However, for various reasons, there has been little research using logistic regression as the base classifier. In this paper, given large unbalanced data, we consider the plausibility of ensemble learning using regularized logistic regression as the base classifier to deal with credit scoring problems. In this research, the data is first balanced and diversified by clustering and bagging algorithms. Then we apply a Lasso-logistic regression learning ensemble to evaluate the credit risks. We show that the proposed algorithm outperforms popular credit scoring models such as decision tree, Lasso-logistic regression and random forests in terms of AUC and F-measure. We also provide two importance measures for the proposed model to identify important variables in the data. PMID:25706988