42 resultados para IGF-IR
Resumo:
Upconversion (UC) is a promising option to enhance the efficiency of solar cells by conversion of sub-bandgap infrared photons to higher energy photons that can be utilized by the solar cell. The UC quantum yield is a key parameter for a successful application. Here the UC luminescence properties of Er3+-doped Gd2O2S are investigated by means of luminescence spectroscopy, quantum yield measurements, and excited state dynamics experiments. Excitation into the maximum of the 4I15/2 → 4I13/2 Er3+ absorption band around 1500 nm induces very efficient UC emission from different Er3+ excited states with energies above the silicon bandgap, in particular, the emission originating from the 4I11/2 state around 1000 nm. Concentration dependent studies reveal that the highest UC quantum yield is realized for a 10% Er3+-doping concentration. The UC luminescence is compared to the well-known Er3+-doped β-NaYF4 UC material for which the highest UC quantum yield has been reported for 25% Er3+. The UC internal quantum yields were measured in this work for Gd2O2S: 10%Er3+ and β-NaYF4: 25%Er3+ to be 12 ± 1% and 8.9 ± 0.7%, respectively, under monochromatic excitation around 1500 nm at a power of 700 W/m2. The UC quantum yield reported here for Gd2O2S: 10%Er3+ is the highest value achieved so far under monochromatic excitation into the 4I13/2 Er3+ level. Power dependence and lifetime measurements were performed to understand the mechanisms responsible for the efficient UC luminescence. We show that the main process yielding 4I11/2 UC emission is energy transfer UC.
Resumo:
Control of metabolic pathways is a major task of the somatotropic axis and its constituents. Insulinlike growth-factor binding proteins (IGFBPs) bind IGF-I and -II and act as carriers and regulators of their activities in blood, body fluids and tissues. Over two periods of physiological adaptation, this study investigated the binding pattern of IGF-I to IGFBPs in the plasma of 50 multiparous Holstein dairy cows and identified relationships with the hepatic mRNA abundance of IGFBPs and plasma IGF-I during the lactational negative energy balance (NEB) and during a deliberately induced NEB by feed restriction. Period 1 lasted from week 3 antepartum (a.p.) to week 12 postpartum (p.p.) and period 2, the period of feed restriction, started at around 100 DIM and lasted for three weeks with a control (C) and a restricted group (R). Blood samples and liver biopsies were collected in week 3 a.p., and in weeks 1 and 4 p.p. of period 1 and in weeks 0 and 3 of period 2. For column chromatography of IGFBPs, plasma samples of all animals were pooled by group and time points of sampling. Plasma IGF-I dropped from week 3 a.p. to week 1 p.p. and thereafter increased until week 0 (period 2) and did not change up to week 3 of period 2. The binding of IGF-I to plasma IGFBP-1 and -2 increased in period 1 from week 3 a.p. to week 4 p.p., while at the same time it decreased for IGFBP-3. During period 2, the binding of IGF-I to plasma IGFBP-1 and -2 decreased for both groups, but less for R cows. In C cows, the IGF-I binding to IGFBP-3 in plasma increased from week 0 to week 3 of period 2, whereas R cows showed a slight decrease. In period 1, hepatic mRNA abundance of IGFBP-3 followed the plasma IGFBP-3 binding in contrast to the mRNA abundances of IGFBP-1 and -2. The latter increased from week 3 a.p. to week 1 p.p. and decreased afterwards whereas IGF-I binding to IGFBP-1 and -2 increased. In week 3 of period 2, the binding of IGF-I to IGFBP-1 and -2 and their hepatic mRNA abundance were higher in R cows compared to C cows. Hepatic mRNA abundance of IGF-I was consistently positively correlated with plasma IGF-I, especially pronounced during the NEBs in week 1 p.p. (period 1) and in week 3 (period 2) in R cows. While no distinct relation between mRNA abundance of IGFBP-1 and plasma IGF-I was evident, the mRNA abundance of IGFBP-2 was inversely related to plasma IGF-I over all experimental time points independent of treatment. The mRNA abundance of IGFBP-3 was particularly correlated with plasma IGF-I during the 2 experimental stages of a NEB. Obviously IGFBP-3, but not IGFBP-1 and -2, binding in plasma closely followed the respective pattern of hepatic mRNA abundance during the entire experimental period. The fact that changes in the different plasma IGFBPs during altering metabolic stages in different stages of lactation do not always strictly follow their mRNA abundance in liver suggests tissues other than the liver flexibly contributing to the IGFBP pool in plasma as well as a partially post-transcriptional regulation of IGFBP synthesis.
Resumo:
Infrared stimulated luminescence (IRSL) and post-IR IRSL are applied to small aliquots and single grains to determine the equivalent dose (De) of eleven alluvial and fluvial sediment samples collected in the Pativilca valley, Central Peru at ca. 10°S latitude. Small aliquot De distributions are rather symmetric and display over-dispersion values between 15 and 46%. Small aliquot g-values range between 4 and 8% per decade for the IRSL and 1 and 2% per decade for the post-IR IRSL signal. The single grain De distributions are highly over-dispersed with some of them skewed to higher doses, implying partial bleaching; this is especially true for the post-IR IRSL. Measurements of a modern analog reveal that residuals due to partial bleaching are present in both the IRSL as well as the post-IR IRSL signal. The g-values of individual grains exhibit a wide range with high individual uncertainties and might contribute significantly to the spread of the single grain De values, at least for the IRSL data. Electron Microprobe Analysis performed on single grains reveal that a varying K-content can be excluded as the origin of over-dispersion. Final ages for the different approaches are calculated using the Central Age Model and the Minimum Age Model (MAM). The samples are grouped into well-beached, potentially well-bleached and partially bleached according to the evaluation of the single grain distributions and the agreement of age estimates between methods. The application of the MAM to the single grain data resulted in consistent age estimates for both the fading corrected IRSL and the post-IR IRSL ages, and suggests that both approaches are suitable for dating these samples. Keywords
Resumo:
Diese Seminararbeit wurde im Rahmen des Seminars Angewandtes Information Retrievalgeschrieben und beschäftigt sich mit der Geschichte der Daten, der Internetgeschichte und dem untrennbar dazugehörenden Information Retrieval, welches als Wiedergewinnung vonbereits zur Verfügung stehenden Daten gesehen werden kann.In einem ersten Teil befasst sich diese Arbeit mit der Geschichte der menschlichen Daten-sammlung und Speicherung. Hier wird die Geschichte von den Anfängen der Datensammlungbis hin zur heutigen digitalen Zeit durchlaufen.Im zweiten Teil werden die Evolution und Funktionsweise verschiedener Systeme vorgestellt,wobei eine Trennung vorgenommen wird in die Geschichte des Information Retrieval, alsAntwort auf die Datenmengen, welche durch die Evolution hervorgebracht wurde, und dannwird auf heutige Trends des Information Retrievals eingegangen. Hierbei werde ich nocheinmal die grundlegenden Probleme der Informationssuche aufzeigen und die aktuellen For-schungen in diesem Gebiet erwähnen.Danach wird ein Fazit gezogen und kritisch Stellung bezüglich der aktuellen Trends einge-nommen. In meinem Schlusswort gebe ich meine Vision einer Suchmaschine wieder, wiediese in Zukunft aussehen könnte
Resumo:
Drugs that inhibit insulin-like growth factor 1 (IGFI) receptor IGFIR were encouraging in early trials, but predictive biomarkers were lacking and the drugs provided insufficient benefit in unselected patients. In this study, we used genetic screening and downstream validation to identify the WNT pathway element DVL3 as a mediator of resistance to IGFIR inhibition. Sensitivity to IGFIR inhibition was enhanced specifically in vitro and in vivo by genetic or pharmacologic blockade of DVL3. In breast and prostate cancer cells, sensitization tracked with enhanced MEK-ERK activation and relied upon MEK activity and DVL3 expression. Mechanistic investigations showed that DVL3 is present in an adaptor complex that links IGFIR to RAS, which includes Shc, growth factor receptor-bound-2 (Grb2), son-of-sevenless (SOS), and the tumor suppressor DAB2. Dual DVL and DAB2 blockade synergized in activating ERKs and sensitizing cells to IGFIR inhibition, suggesting a nonredundant role for DVL3 in the Shc-Grb2-SOS complex. Clinically, tumors that responded to IGFIR inhibition contained relatively lower levels of DVL3 protein than resistant tumors, and DVL3 levels in tumors correlated inversely with progression-free survival in patients treated with IGFIR antibodies. Because IGFIR does not contain activating mutations analogous to EGFR variants associated with response to EGFR inhibitors, we suggest that IGF signaling achieves an equivalent integration at the postreceptor level through adaptor protein complexes, influencing cellular dependence on the IGF axis and identifying a patient population with potential to benefit from IGFIR inhibition.
Resumo:
Ein soziolinguistisch angelegtes Projekt der Universität Bern greift die Idee der „language related major life events“ – die neue sprachliche und soziale Räume schaffen – auf. Das Forschungsprojekt besteht aus drei Modulen. Module 1 und 2 untersuchen Personen, die beim Übergang von der Grundausbildung in eine weiterführende Ausbildung mit einem Wechsel der Umgebungssprache konfrontiert sind: und zwar (1) frankofone Lernende in Biel/Bienne, die – im Kontext dieser zweisprachigen Stadt – neben ihrer Herkunftssprache mit Schweizerdeutsch konfrontiert sind, und (2) frankofone und italofone Studierende, die an Universitäten und Hochschulen der deutschen Schweiz studieren müssen, weil es das betreffende Fach weder in der Romandie noch im Tessin gibt. Im Modul 3 werden zwei Personengruppen untersucht (italienische MigrantInnen und Deutsch-schweizerInnen), die sich vor, im und nach dem Prozess der Pensionierung befinden, die bestehende berufliche Netzwerke verlieren, eventuell neue aufbauen und denen sich neue kommunikative Anforderungen stellen. Im Rahmen dieses Forschungsprojekts wurden wir mit der Frage konfrontiert, wie die Sprachkenntnisse erfasst und analysiert werden könnten. Die erste Hürde bestand darin, dass wir als Ausgangslage nur ein bis zwei Interviews in der Muttersprache der Probanden (Italienisch oder Französisch) führen würden und nicht klar war, wie wir in diesem Kontext zu zuverlässigen Sprachdaten auf Schweizerdeutsch kommen: - Sollten wir selbst oder eine zweite Person die Fragen stellen? oder - Wie standardisieren wir den Fragenkatalog? Nach langer Suche nach einem geeigneten Testinstrument entschieden wir uns eine eigene Methode zu entwickeln die auf SOPI/OPI basiert. Auch hier stellten sich mehrere Fragen, wie zum Beispiel: - Welchen Schweizerdeutsch Dialekt wird verwendet? - Welche Fragen stellen wir (unterschiedliche Probandengruppen)? - Wie stellen wir einen wachsenden Schwierigkeitsgrad her? Während der Durchführung der Tests begegneten wir neuen Problematiken. Aufgrund der negativ konnotierten Testsituation fühlten sich einzelne Probanden z.B. angegriffen. Weiter wurden wir mit dem Beobachterparadoxon konfrontiert und konnten bei wiederholten Tests Gewöhnungseffekte feststellen. Zusätzlich erwiesen sich einige Fragen als problematisch (z.B. in diesem Kontext nicht sinnvoll oder verschieden interpretierbar). Am Ende werden wir mit den verschieden Problemen der Analyse konfrontiert sein. Wir fragen uns aufgrund welcher Kriterien eine Analyse sinnvoll ist und ob unsere Daten überhaupt vergleichbar sind. In unserem Paper möchten wir die oben genannten methodischen Probleme darstellen und unsere Lösungsansätze diskutieren.
Resumo:
Intensified aquaculture has strong impact on fish health by stress and infectious diseases and has stimulated the interest in the orchestration of cytokines and growth factors, particularly their influence by environmental factors, however, only scarce data are available on the GH/IGF-system, central physiological system for development and tissue shaping. Most recently, the capability of the host to cope with tissue damage has been postulated as critical for survival. Thus, the present study assessed the combined impacts of estrogens and bacterial infection on the insulin-like growth factors (IGF) and tumor-necrosis factor (TNF)-α. Juvenile rainbow trout were exposed to 2 different concentrations of 17β-estradiol (E2) and infected with Yersinia ruckeri. Gene expressions of IGF-I, IGF-II and TNF-α were measured in liver, head kidney and spleen and all 4 estrogen receptors (ERα1, ERα2, ERβ1 and ERβ2) known in rainbow trout were measured in liver. After 5 weeks of E2 treatment, hepatic up-regulation of ERα1 and ERα2, but down-regulation of ERß1 and ERß2 were observed in those groups receiving E2-enriched food. In liver, the results further indicate a suppressive effect of Yersinia-infection regardless of E2-treatment on day 3, but not of E2-treatment on IGF-I whilst TNF-α gene expression was not influenced by Yersinia-infection but was reduced after 5 weeks of E2-treatment. In spleen, the results show a stimulatory effect of Yersinia-infection, but not of E2-treatment on both, IGF-I and TNF-α gene expressions. In head kidney, E2 strongly suppressed both, IGF-I and TNF-α. To summarise, the treatment effects were tissue- and treatment-specific and point to a relevant role of IGF-I in infection.
Resumo:
Glucose transport to the fetus across the placenta takes place via glucose transporters in the opposing faces of the barrier layer, the microvillous and basal membranes of the syncytiotrophoblast. While basal membrane content of the GLUT1 glucose transporter appears to be the rate-limiting step in transplacental transport, the factors regulating transporter expression and activity are largely unknown. In view of the many studies showing an association between IGF-I and fetal growth, we investigated the effects of IGF-I on placental glucose transport and GLUT1 transporter expression. Treatment of BeWo choriocarcinoma cells with IGF-I increased cellular GLUT1 protein. There was increased basolateral (but not microvillous) uptake of glucose and increased transepithelial transport of glucose across the BeWo monolayer. Primary syncytial cells treated with IGF-I also demonstrated an increase in GLUT1 protein. Term placental explants treated with IGF-I showed an increase in syncytial basal membrane GLUT1 but microvillous membrane GLUT1 was not affected. The placental dual perfusion model was used to assess the effects of fetally perfused IGF-I on transplacental glucose transport and syncytial GLUT1 content. In control perfusions there was a decrease in transplacental glucose transport over the course of the perfusion, whereas in tissues perfused with IGF-I through the fetal circulation there was no change. Syncytial basal membranes from IGF-I perfused tissues showed an increase in GLUT1 content. These results demonstrate that IGF-I, whether acting via microvillous or basal membrane receptors, increases the basal membrane content of GLUT1 and up-regulates basal membrane transport of glucose, leading to increased transepithelial glucose transport. These observations provide a partial explanation for the mechanism by which IGF-I controls nutrient supply in the regulation of fetal growth.
Resumo:
BACKGROUND Sutureless aortic valve replacement (SU-AVR) is an innovative approach which shortens cardiopulmonary bypass and cross-clamp durations and may facilitate minimally invasive approach. Evidence outlining its safety, efficacy, hemodynamic profile and potential complications is replete with small-volume observational studies and few comparative publications. METHODS Minimally invasive aortic valve surgery and high-volume SU-AVR replacement centers were contacted for recruitment into a global collaborative coalition dedicated to sutureless valve research. A Research Steering Committee was formulated to direct research and support the mission of providing registry evidence warranted for SU-AVR. RESULTS The International Valvular Surgery Study Group (IVSSG) was formed under the auspices of the Research Steering Committee, comprised of 36 expert valvular surgeons from 27 major centers across the globe. IVSSG Sutureless Projects currently proceeding include the Retrospective and Prospective Phases of the SU-AVR International Registry (SU-AVR-IR). CONCLUSIONS The global pooling of data by the IVSSG Sutureless Projects will provide required robust clinical evidence on the safety, efficacy and hemodynamic outcomes of SU-AVR.
Resumo:
Endometriosis affects approximately 15% of reproductive aged women and is associated with chronic pelvic pain and infertility. However, the molecular mechanisms by which endometriosis impacts fertility are poorly understood. The developmentally regulated, imprinted H19 long noncoding RNA (lncRNA) functions to reduce the bioavailability of microRNA let-7 by acting as a molecular sponge. Here we report that H19 expression is significantly decreased in the eutopic endometrium of women with endometriosis as compared to normal controls. We show that decreased H19 increases let-7 activity, which in turn inhibits Igf1r expression at the post-transcriptional level, thereby contributing to reduced proliferation of endometrial stromal cells. We propose that perturbation of this newly identified H19/Let-7/IGF1R regulatory pathway may contribute to impaired endometrial preparation and receptivity for pregnancy in women with endometriosis. Our finding represents the first example of a lncRNA-based mechanism in endometriosis and its associated infertility, thus holding potential in the development of novel therapeutics for women with endometriosis and infertility.