The formation of ultrafine ferrite through static transformation in low carbon steels

A novel approach was used to produce an ultrafine grain structure in low carbon steels with a wide range of hardenability. This included warm deformation of supercooled austenite followed by reheating in the austenite region and cooling (RHA). The ultrafine ferrite structure was independent of steel composition. However, the mechanism of ferrite refinement changed with the steel quench hardenability. In a relatively low hardenable steel, the ultrafine structure was produced through dynamic strain induced transformation, whereas the ferrite refinement was formed by static transformation in steels with high quench hardenability. The use of a model Ni-30Fe austenitic alloy revealed that the deformation temperature has a strong effect on the nature of the intragranular defects. There was a transition temperature below which the cell dislocation structure changed to laminar microbands. It appears that the extreme refinement of ferrite is due to the formation of extensive high angle intragranular defects at these low deformation temperature that then act as sites for static transformation. © 2008 World Scientific Publishing Company.

Interaction between recrystallization and strain-induced precipitation in a high Nb- and N-bearing austenitic stainless steel: influence of the interpass time

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Theileria-induced leukocyte transformation

The intracellular protozoan parasites Theileria parva and T. annulata transform the cells they infect, inducing uncontrolled proliferation. This is not a trivial event as, in addition to permanently switching on the complex pathways that govern all steps of the cell cycle, the built-in apoptotic safety mechanisms that prevent 'illegitimate' cell replication also need to be inactivated. Recent experiments show that the NF-kappa B and phosphoinositide 3-kinase (PtdIns-3K) pathways are important participants in the transformation process. I kappa B kinase (IKK), a pivotal kinase complex in the NF-kappa B pathway, is recruited to the parasite surface where it becomes activated. The PtdIns-3K/Akt/PKB pathway is also constitutively activated in a parasite-dependent manner, but contrary to IKK, activation is probably not triggered by direct association with the parasite.

Oral prednisolone induced acute generalized exanthematous pustulosis due to corticosteroids of group A confirmed by epicutaneous testing and lymphocyte transformation tests

BACKGROUND: Acute generalized exanthematous pustulosis (AGEP) is a rare cutaneous eruption which is often provoked by drugs. CASE REPORT: We report 2 cases of AGEP which showed rapidly spreading pustular eruptions accompanied by malaise, fever and neutrophilia after the administration of systemic prednisolone (corticosteroid of group A, hydrocortisone type). The histological examination showing neutrophilic subcorneal spongiform pustules was consistent with the diagnosis of AGEP. In both cases the rash cleared within a week upon treatment with topical steroids (corticosteroid of group D1, betamethasonedipropionate type and corticosteroid of group D2, hydrocortisone-17-butyrate type). Three months after recovery, the sensitization to corticosteroids of group A was confirmed by epicutaneous testing and positive lymphocyte transformation tests. CONCLUSION: These cases show that systemic corticosteroids can induce AGEP and demonstrate that epicutaneous testing and lymphocyte transformation tests may be helpful in identifying the causative drug. Our data support previous reports indicating an important role for drug-specific T cells in inducing neutrophil inflammation in this disease.

MONOCLONAL ANTIBODY CHARACTERIZATION OF RAT TRANSFORMATION ASSOCIATED PROTEINS INDUCED BY MOLONEY MURINE SARCOMA VIRUS

By the use of Moloney murine sarcoma virus (Mo-MSV)-induced rat bone tumor (RBT) cells as immunogens, and the hybridoma technique, a mouse hybridoma clone was isolated in Dr. Chan's lab (Chan et al., 1983), which produced a monoclonal antibody, designated MC. MC detected specific antigens in three different Mo-MSV-transformed rat cell lines: 78A1 WRC, RBT and 6M2 (NRK cells infected with the ts110 mutant of Mo-MSV), but not in their untransformed counterparts. These antigens are tentatively termed transformation associated proteins (TAP). In this study, TAP were hypothesized to be the rat specific proteins which are activated by Mo-MSV and play an important role in cellular transformation, and were further investigated. Their properties are summarized as follows: (1) TAP may represent cellular products localized in the cytoplasm of 6M2 cells. (2) The expression of TAP is temperature-sensitive and related to cellular transformation, and probably activated by the v-mos gene products. The optimal temperature for the expression of both P85('gag-mos), the only known viral transforming protein in 6M2 cells, and TAP was 28(DEGREES)C. The expression of both P85('gag-mos) and TAP was proportional to the degree of transformation of 6M2 cells. (3) There were four antigenically-related forms of intracellular TAP (P66, P63, P60 and P58) in 6M2 cells. After synthesis, the 58Kd TAP was probably converted to one of the other three forms. These three polypeptides (P66, P63 and P60) were rapidly converted to two (P68 and P64) and subsequently secreted to the extracellular medium with a 50% secretion rate of 78 min. The conversion of these molecular sizes of TAP is probably related to glycosylation. Inhibition of TAP glycosylation by 0.5 ug/ml of tunicamycin could retard the secretion rate of TAP by 39%. (4) TAP are phosphoproteins, but not associated with any protein kinase activity. (5) TAP have been purified, and found to be mitogenic NRK-2 cells. TAP can bind to the receptors of NRK-2 cells with a K(,d) of 1.4 pM and with about 2 x 10('5) binding sites for TAP per NRK-2 cell. (6) Some weak proteolytic activity was found to associate with purified TAP. ^

Mechanisms of TGF-beta1-induced neuronal plasticity in Aplysia

Transforming growth factor beta-1 (TGF-β1) is a cytokine and neurotrophic factor whose neuromodulatory effects in Aplysia californica were recently described. Previous results demonstrated that TGF-β1 induces long-term increases in the efficacy of sensorimotor synapses, a neural correlate of sensitization of the defensive tail withdrawal reflex. These results provided the first evidence that a neurotrophic factor regulates neuronal plasticity associated with a simple form of learning in Aplysia, and raised many questions regarding the nature of the modulation. No homologs of TGF-β had previously been identified in Aplysia, and thus, it was not known whether components of TGF-β1 signaling pathways were present in Aplysia. Furthermore, the signaling mechanisms engaged by TGF-β1 had not been identified, and it was not known whether TGF-β1 regulated other aspects of neuronal function.^ The present investigation into the actions of TGF-β1 was initiated by examining the distribution of the type II TGF-β1 receptor, the ligand binding receptor. The receptor was widely distributed in the CNS and most neurons exhibited somatic and neuritic immunoreactivity. In addition, the ability of TGF-β1 to activate the cAMP/PKA and MAPK pathways, known to regulate several important aspects of neuronal function, was examined. TGF-β1 acutely decreased cAMP levels in sensory neurons, activated MAPK and triggered translocation of MAPK to the nucleus. MAPK activation was critical for both short- and long-term regulation of neuronal function by TGF-β1. TGF-β1 acutely decreased synaptic depression induced by low frequency stimuli in a MAPK-dependent manner. This regulation may result, at least in part, from the modulation of synapsin, a major peripheral synaptic vesicle protein. TGF-β1 stimulated MAPK-dependent phosphorylation of synapsin, a process believed to regulate synaptic vesicle mobilization from reserve to readily-releasable pools of neurotransmitter. In addition to its acute effect on synaptic efficacy, TGF-β1 also induced long-term increases in sensory neuron excitability. Whereas transient exposure to TGF-β1 was not sufficient to drive short-or long-term changes in excitability, prolonged exposure to TGF-β1 induced long-term changes in excitability that depended on MAPK. The results of these studies represent significant progress toward an understanding of the role of TGF-β1 in neuronal plasticity. ^

Effect of Thermal Relaxation on LSP Induced Residual Stresses and Fatigue Life Enhancement of AISI 316L stainless steel

Effect of Thermal Relaxation on LSP Induced Residual Stresses and Fatigue Life Enhancement of AISI 316L stainless steel

Association of arsenic-induced malignant transformation with DNA hypomethylation and aberrant gene expression

Inorganic arsenic, a human carcinogen, is enzymatically methylated for detoxication, consuming S-adenosyl-methionine (SAM) in the process. The fact that DNA methyltransferases (MeTases) require this same methyl donor suggests a role for methylation in arsenic carcinogenesis. Here we test the hypothesis that arsenic-induced initiation results from DNA hypomethylation caused by continuous methyl depletion. The hypothesis was tested by first inducing transformation in a rat liver epithelial cell line by chronic exposure to low levels of arsenic, as confirmed by the development of highly aggressive, malignant tumors after inoculation of cells into Nude mice. Global DNA hypomethylation occurred concurrently with malignant transformation and in the presence of depressed levels of S-adenosyl-methionine. Arsenic-induced DNA hypomethylation was a function of dose and exposure duration, and remained constant even after withdrawal of arsenic. Hyperexpressibility of the MT gene, a gene for which expression is clearly controlled by DNA methylation, was also detected in transformed cells. Acute arsenic or arsenic at nontransforming levels did not induce global hypomethylation of DNA. Whereas transcription of DNA MeTase was elevated, the MeTase enzymatic activity was reduced with arsenic transformation. Taken together, these results indicate arsenic can act as a carcinogen by inducing DNA hypomethylation, which in turn facilitates aberrant gene expression, and they constitute a tenable theory of mechanism in arsenic carcinogenesis.

Differentially expressed protein Pdcd4 inhibits tumor promoter-induced neoplastic transformation

An mRNA differential display comparison of mouse JB6 promotion-sensitive (P+) and -resistant (P−) cells identified a novel gene product that inhibits neoplastic transformation. The JB6 P+ and P− cells are genetic variants that differ in their transformation response to tumor promoters; P+ cells form anchorage-independent colonies that are tumorigenic, and P− cells do not. A differentially displayed fragment, A7-1, was preferentially expressed in P− cells at levels ≥10-fold those in P+ cells, making its mRNA a candidate inhibitor of neoplastic transformation. An A7-1 cDNA was isolated that was identical to murine Pdcd4 gene cDNAs, also known as MA-3 or TIS, and analogous to human H731 and 197/15a. Until now, the function of the Pdcd4 protein has been unknown. Paralleling the mRNA levels, Pdcd4 protein levels were greater in P− than in P+ cells. Pdcd4 mRNA was also expressed at greater levels in the less progressed keratinocytes of another mouse skin neoplastic progression series. To test the hypothesis that Pdcd4 inhibits tumor promoter-induced transformation, stable cell lines expressing antisense Pdcd4 were generated from parental P− cells. The reduction of Pdcd4 proteins in antisense lines was accompanied by acquisition of a transformation-sensitive (P+) phenotype. The antisense-transfected cells were reverted to their initial P− phenotype by overexpression of a Pdcd4 sense fragment. These observations demonstrate that the Pdcd4 protein inhibits neoplastic transformation.

Rapidly induced auditory plasticity: The ventriloquism aftereffect

Cortical representational plasticity has been well documented after peripheral and central injuries or improvements in perceptual and motor abilities. This has led to inferences that the changes in cortical representations parallel and account for the improvement in performance during the period of skill acquisition. There have also been several examples of rapidly induced changes in cortical neuronal response properties, for example, by intracortical microstimulation or by classical conditioning paradigms. This report describes similar rapidly induced changes in a cortically mediated perception in human subjects, the ventriloquism aftereffect, which presumably reflects a corresponding change in the cortical representation of acoustic space. The ventriloquism aftereffect describes an enduring shift in the perception of the spatial location of acoustic stimuli after a period of exposure of spatially disparate and simultaneously presented acoustic and visual stimuli. Exposure of a mismatch of 8° for 20–30 min is sufficient to shift the perception of acoustic space by approximately the same amount across subjects and acoustic frequencies. Given that the cerebral cortex is necessary for the perception of acoustic space, it is likely that the ventriloquism aftereffect reflects a change in the cortical representation of acoustic space. Comparisons between the responses of single cortical neurons in the behaving macaque monkey and the stimulus parameters that give rise to the ventriloquism aftereffect suggest that the changes in the cortical representation of acoustic space may begin as early as the primary auditory cortex.

Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis

Signal transducer and activator of transcription (STAT) proteins perform key roles in mediating signaling by cytokines and growth factors, including platelet-derived growth factor (PDGF). In addition, Src family kinases activate STAT signaling and are required for PDGF-induced mitogenesis in normal cells. One STAT family member, Stat3, has been shown to have an essential role in cell transformation by the Src oncoprotein. However, the mechanisms by which STAT-signaling pathways contribute to mitogenesis and transformation are not fully defined. We show here that disruption of Stat3 signaling by using dominant-negative Stat3β protein in NIH 3T3 fibroblasts suppresses c-Myc expression concomitant with inhibition of v-Src-induced transformation. Ectopic expression of c-Myc is able to partially reverse this inhibition, suggesting that c-Myc is a downstream effector of Stat3 signaling in v-Src transformation. Furthermore, c-myc gene knockout fibroblasts are refractory to transformation by v-Src, consistent with a requirement for c-Myc protein in v-Src transformation. In normal NIH 3T3 cells, disruption of Stat3 signaling with dominant-negative Stat3β protein inhibits PDGF-induced mitogenesis in a manner that is reversed by ectopic c-Myc expression. Moreover, inhibition of Src family kinases with the pharmacologic agent, SU6656, blocks Stat3 activation by PDGF. These findings, combined together, delineate the signaling pathway, PDGF → Src → Stat3 → Myc, that is important in normal PDGF-induced mitogenesis and subverted in Src transformation.