The Effect of Ferrite Embrittlement in Duplex Steel on Fatigue Crack Propagation from the Low (LCF) to the Very High Cycle Fatigue (VHCF) Regime

The excellent combination of mechanical properties and corrosion resistance of duplex stainless steel is obtained from balanced amount of ferrite and austenite in the microstructure. However, this grade of steel embrittles when exposed in the temperature range of 280–500ºC limiting its application to temperatures below 280ºC. To study the effect of embrittlemnt on fatigue behavior at high strain ranges, plastic-strain- controlled LCF test and at low strain ranges, stress-controlled HCF/VHCF tests were conducted on 1.4462 duplex steel and accompanied by SEM analysis in combination with EBSD. Extensive TEM was done to study the micromechanism of fatigue crack initiation and propagation across the strain ranges

Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

<p>Abstract</p> <p>Background</p> <p>The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I) gene therapy for the treatment of estrogen-induced prolactinomas in rats.</p> <p>Results</p> <p>Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E₂) in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL). As expected, serum PRL increased progressively and 23 days after implanting the E₂capsules (Experimental day 0), circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E₂-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI), or a vector (RAd-GFP) expressing the gene for green fluorescent protein (GFP). Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS) and volume density (VD) induced by E₂treatment.</p> <p>Conclusion</p> <p>We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.</p

Epidermal growth factor targeting of bacteriophage to the choroid plexus for gene delivery to the central nervous system via cerebrospinal fluid

Because the choroid plexus normally controls the production and composition of cerebrospinal fluid and, as such, its many functions of the central nervous system, we investigated whether ligand-mediated targeting could deliver genes to its secretory epithelium. We show here that when bacteriophages are targeted with epidermal growth factor, they acquire the ability to enter choroid epithelial cells grown in vitro as cell cultures, ex vivo as tissue explants or in vivo by intracerebroventricular injection. The binding and internalization of these particles activate EGF receptors on targeted cells, and the dose- and time-dependent internalization of particles is inhibited by the presence of excess ligand. When the phage genome is further reengineered to contain like green fluorescent protein or firefly luciferase under control of the cytomegalovirus promoter, gene expression is detectable in the choroid plexus and ependymal epithelium by immunohistochemistry or by noninvasive imaging, respectively. Taken together, these data support the hypothesis that reengineered ligand-mediated gene delivery should be considered a viable strategy to increase the specificity of gene delivery to the central nervous system and bypass the blood-brain barrier so as to exploit the biological effectiveness of the choroid plexus as a portal of entry into the brain

Ontogenetic studies on the determination of the apical meristem in racemose inflorescences

This thesis presents a comparative developmental study of inflorescences and focuses on the production of the terminal flower (TF). Morphometric attributes of inflorescence meristems (IM) were obtained throughout the ontogeny of inflorescence buds with the aim of describing possible spatial constraints that could explain the failure in developing the TF. The study exposes the inflorescence ontogeny of 20 species from five families of the Eudicots (Berberidaceae, Papaveraceae-Fumarioideae, Rosaceae, Campanulaceae and Apiaceae) in which 745 buds of open (i.e. without TF) and closed (i.e. with TF) inflorescences were observed under the scanning electron microscope.rnThe study shows that TFs appear on IMs which are 2,75 (se = 0,38) times larger than the youngest lateral reproductive primordium. The shape of these IMs is characterized by a leaf arc (phyllotactic attribute) of 91,84° (se = 7,32) and a meristematic elevation of 27,93° (se = 5,42). IMs of open inflorescences show a significant lower relative surface, averaging 1,09 (se=0,26) times the youngest primordium size, which suggests their incapacity for producing TFs. The relative lower size of open IMs is either a condition throughout the complete ontogeny (‘open I’) or a result from the drastic reduction of the meristematic surface after flower segregation (‘open II’). rnIt is concluded that a suitable bulge configuration of the IM is a prerequisite for TF formation. Observations in the TF-facultative species Daucus carota support this view, as the absence of the TF in certain umbellets is correlated with a reduction of their IM dimensions. A review of literature regarding histological development of IMs and genetic regulation of inflorescences suggests that in ‘open I’ inflorescences, the histological composition and molecular activity at the tip of the IM could impede the TF differentiation. On the other side, in ‘open II’ inflorescences, the small final IM bulge could represent a spatial constraint that hinders the differentiation of the TF. The existence of two distinct kinds of ontogenies of open inflorescences suggests two ways in which the loss of the TF could have occurred in the course of evolution.rnDie Dissertation beinhaltet eine vergleichende Studie zur Entwicklung von Blütenständen, wobei der Schwerpunkt auf der Bildung bzw. dem Fehlen von Endblüten (EB) liegt. Morphometrische Veränderungen, die während der Ontogenie der Blütenstandsknospen am Infloreszenzmeristem (IM) auftreten, wurden erstmals ermittelt und quantifiziert, um eventuelle räumliche Zwänge, die das Ausfallen der EB erklären könnten, zu beschreiben. Die Studie umfasst die Infloreszenzontogenie von 20 Arten aus fünf Familien der Eudicotyledonae (Berberidaceae, Papaveraceae-Fumarioideae, Rosaceae, Campanulaceae and Apiaceae) mit offenen (ohne EB) und geschlossenen (mit EB) Blütenständen. Sie basiert auf der Analyse von 745 Infloreszenzknospen unter dem Rasterelektronmikroskop.rnDie Ergebnisse zeigen, dass sich Endblüten nur an Infloreszenzmeristemen entwickeln, die 2,75 (se = 0,38) Mal so groß sind wie ihr jüngstes Seitenprimordium. Ihre Form wird weiterhin von einem Primordienansatz von 91,84° (se = 7,32) und einer Wölbung von 27,93° (se = 5,42) bestimmt. Infloreszenzmeristeme offener Blütenständen zeigen dagegen mit nur 1,09-facher (se = 0,26) Größe des jüngsten Seitenprimordiums signifikant kleinere Werte. Dies deutet darauf hin, dass eine bestimmte Gewebemasse für die Endblütenbildung zur Verfügung stehen muss. Die relativ kleineren IMs sind entweder die gesamte Ontogenie hindurch vorhanden (‚open I’,) oder entstehen erst im Zuge der Blütenausgliederung durch die rasche Abnahme des meristematischen Gewebes (‘open II’).rnBeobachtungen an Daucus carota unterstützen die Annahme, dass eine passende IM-Konfiguration vorliegen muss, bevor eine EB gebildet werden kann. In dieser Art werden fakultativ Endblüten gebildet, wobei das Fehlen der EB immer mit einer Reduktion der IM-Dimensionen einhergeht.rnUmfassende Literaturrecherchen weisen darauf hin, dass das Fehlen einer EB in ‚open I’ Infloreszenzen auf der noch vegetativ geprägten histologischen Zonierung und genetischen Aktivität an der Spitze des IMs beruhen könnte. Demgegenüber könnten die am Ende der Blütenausgliederung klein gewordenen IMs der ‘open II’ Infloreszenzen aufgrund ihrer engen räumlichen Verhältnisse nicht mehr in der Lage sein, eine Endblüte zu produzieren. Der Nachweis von zwei unterschiedlichen Ontogenien in offenen Blütenständen deutet darauf hin, dass auch im Laufe der Evolution die Endblüte durch unterschiedliche Prozesse entstanden bzw. verloren gegangen ist. r

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Volume: 128Start Page: 213End Page: 21

Influence of dislocation glide on the spinodal decomposition of fatigued duplex stainless steels

International audienceThe present work is focused on assessing the influence of dislocation movement on spinodal decomposition through scanning transmission electron microscopy (STEM) in combination with energy dispersive X-ray spectroscopy (EDS) analysis in aged duplex stainless steel (DSS) S32750. Dislocation bands and microbands are the prominent dislocation arrangements observed in fatigue tested aged samples. By EDS measurements it was found that the spinodal decomposition was dissolved inside these dislocations structures. Therefore, the mechanism of microband formation developed in the ferritic phase during cycling seems to be responsible for the demodulation of the spinodal decomposition and cyclic softening of the aged DSS

Strain heterogeneities between phases in a duplex stainless steel. Comparison between measures and simulation

International audienc

Restorative effect of insulin-like growth Factor I gene therapy in the hypothalamus of senile rats with dapaminergic neurodegeneration

Insuline-like factor I (IGF-I) is emerging as a powerful reuroprotective molecule which is strongly induced in the central nervous system after different insults

IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain

Falomir-Lockhart E, Dolcetti FJC, Herrera ML, et al. IGF-1 Gene Transfer Modifies Inflammatory Environment and Gene Expression in the Caudate-Putamen of Aged Female Rat Brain. Molecular Neurobiology . 2022.Brain aging is characterized by chronic neuroinflammation caused by activation of glial cells, mainly microglia, leading to alterations in homeostasis of the central nervous system. Microglial cells are constantly surveying their environment to detect and respond to diverse signals. During aging, microglia undergoes a process of senescence, characterized by loss of ramifications, spheroid formation, and fragmented processes, among other abnormalities. Therefore, the study of changes in microglia during is of great relevance to understand age-related declines in cognitive and motor function. We have targeted the deleterious effects of aging by implementing IGF-1 gene transfer, employing recombinant adenoviral vectors (RAds) as a delivery system. In this study, we performed intracerebroventricular (ICV) RAd-IGF-1 or control injection on aged female rats and evaluated its effect on caudate-putamen unit (CPu) gene expression and inflammatory state. Our results demonstrate that IGF-1 overexpression modified aged microglia of the CPu towards an anti-inflammatory condition increasing the proportion of double immuno-positive Iba1+Arg1+ cells. We also observed that phosphorylation of Akt was increased in animals treated with RAd-IGF-1. Moreover, IGF-1 gene transfer was able to regulate CPu pro-inflammatory environment in female aged rats by down-regulating the expression of genes typically overexpressed during aging. RNA-Seq data analysis identified 97 down-modulated DEG in the IGF-1 group as compared to the DsRed one. Interestingly, 12 of these DEG are commonly overexpressed during aging, and 9 out of 12 are expressed in microglia/macrophages and are involved in different processes that lead to neuroinflammation and/or neuronal loss. Finally, we observed that IGF-1 overexpression led to an improvement in motor functions. Although further studies are necessary, with the present results, we conclude that IGF-1 gene transfer is modifying both the pro-inflammatory environment and activation of microglia/macrophages in CPu. In this regard, IGF-1 gene transfer could counteract the neuroinflammatory effects associated with aging and improve motor functions in senile animals. © 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature