Early Stages Of Transformation Research Articles

Post-Soviet transformation of Lithuanian state cultural policy: the meanings of democratisation

This paper presents a general overview of the process of the democratisation of cultural policy in Lithuania by exploring explicit arguments about democratisation in debates and policy documents in Lithuania (1988–2011). At the early stage of transformation (1988–1992), democratisation was envisaged as the administrative decentralisation of political institutions, particularly the Ministry of Culture, and as the introduction of democratic principles, such as freedom of speech and cultural self-regulation. More substantial meanings of democratisation were articulated in debates about ethnic diversity and social equality. The study reveals tensions between the values of high culture and pop culture and the unitary notion of Lithuanian national ethnic culture and the cultures of national minorities. At a later stage, the salience of the ethnic dimension decreased when the democratisation of cultural policy was conceptualised in relation to the knowledge economy, which required revision of the early post-Soviet confrontation between culture and its economic use.

Evidence for Point Transformations in Photoactive Molecular Crystals by the Photoinduced Creation of Diffuse Diffraction Patterns

Time-resolved diffuse X-ray scattering is one powerful method for monitoring the progression from the creation of local structural changes inside a crystalline material up to the transformation of the whole crystalline bulk. In this work, we study the mechanism of phototransformation of a molecular crystal by time-resolved diffuse X-ray scattering. Here, an optical excitation source, like a pulsed laser, initiates structural transformations which are monitored by X-ray scattering techniques. We have studied the dimerization process of the molecular switch α-styrylpyrylium (trifluoromethanesulfonate) TFMS, in particular for understanding whether cooperative effects influence the changes of the structure in the bulk and its periodicity. Upon illumination with optical light, α-styrylpyrylium TFMS instantaneously photoswitches. Depending on the optical fluence, X-ray diffuse planes are observed prior to phototransformation of the bulk. In the early stages of transformation, the analysis reveals systems of randomly distributed islands of product clusters with gradual growth in size and amount. The degree of transformation follows the optical excitation profile, i.e., the spatial absorption of the laser beam. In the present studies, no influence of cooperativity on the photodimerization process has been found.

Bainite Growth Behavior at the Early Stage of Transformation at Low Temperature

The growth behavior of the bainite obtained by short-time isothermal transformation at 200°C in the high carbon silicon-containing steel has been investigated. It is found that the bainite appears the plates consisting of single ferrite phase, and that both the lateral growth and longitudinal growth of bainite have weak ability to traverse the lattice-distortion strain fields and grain interface of austenite.

Growth Kinetics of Proeutectoid Ferrite in Fe-0.1C-1.5Mn-1Si Quaternary and Fe-0.1C-1.5Mn-1Si-0.2Al Quinary Alloys

The growth kinetics of proeutectoid ferrite in the early stages of transformation were studied in Fe-0.1C-1.5Mn-1Si (mass pct) quaternary and Fe-0.1C-1.5Mn-1Si-0.2Al quinary alloys. The observed kinetic transition temperatures from partitioned slow growth to unpartitioned fast growth of ferrite in both alloys are in good agreement with predictions using a local equilibrium model for multicomponent systems. The measured parabolic growth rate constants were smaller than those calculated assuming paraequilibrium in the unpartitioned growth region, but the difference between the measured and the calculated growth rate constants gradually diminished with a decreasing reaction temperature. The dissipation of driving force, derived from the diffusion of the substitutional solute within the transformation interface, possibly constitutes a major part of the discrepancy between the measured and the calculated growth kinetics.

Slow Bainite: an Opportunity to Determine the Carbon Content of the Bainitic Ferrite during Growth

The amount of carbon in solid solution in bainitic ferrite at the early stage of transformation has been directly determined by atom probe tomography at 200 °C, taking advantage of the extremely slow transformation kinetics of a novel nanocrystalline steel. Results demonstrated that the original bainitic ferrite retains much of the carbon content of the parent austenite providing strong evidence that bainite transformation is essentially displacive in nature.

Abstract 797: Characterization of endogenous antibodies to tumor

Abstract Early detection of malignancy is crucial for long-term survival in patients with various types of cancer; however, this remains a challenge in a wide variety of tumors. This study tests whether a patient's own antibodies can be used diagnostically for early detection. It has been proposed that the body is undergoing continuous surveillance by the immune system, with elimination of newly transformed cells. Cancer becomes a clinical problem when the immune system fails to eliminate these cells. Many studies have looked at the immune system, particularly antibodies, as a therapeutic tool against tumor-associated antigens. However, single antigens are rarely sensitive or specific for a certain tumor type. The use of panels of antigens and antibodies has increased the sensitivity of tumor detection, however not sufficiently. We tested if the polyclonal spectra of antibodies that an individual creates can still detect tumors even if the immune system cannot eliminate the tumor. These antibodies will vary considerably in affinity and specificity. The goal was to determine if they could serve as a dependable and reliable means to detect microscopic foci of tumor, and distinguish transformed from normal tissue. We therefore tested for the presence of endogenous antibodies in tissue from multiple mouse models of cancer, including models consisting of over expression of an oncogene in addition to deletion of a tumor suppressor gene. We obtained tissue from four mouse models of tumor: liver tissue from transgenic alb-myc mice, breast tissue from transgenic MMTV-neu mice, and prostate tissue from two prostate models (a transgenic Pb-myc model and a knock-out PTEN model). These were compared to matched tissue samples from wild-type mice. Paraffin embedded and frozen section slides of test and matched wild-type tissue were tested for the presence of endogenous antibody with immunofluorescence, using a rabbit secondary anti-mouse IgG. Immunofluorescence with a goat anti-rabbit IgG served as a negative control. There was a significantly higher intensity of immunofluorescence in tissue from mice genetically engineered to have tumors compared to the wild-type mice. Adjacent sections stained with H&E were evaluated by a veterinary histo-pathologist in a double-blind study. Areas marked as altered by H&E were significantly enhanced in antibody binding. Similar results were observed in the liver, prostate and breast cancer models. No signal was observed with the goat anti-rabbit negative control. The results indicate that the spectra of endogenous antibodies have the potential to detect these genetically engineered tumors at early stages of transformation. The success of this approach opens the possibility of using these antibodies both diagnostically and therapeutically. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 797. doi:10.1158/1538-7445.AM2011-797

Abstract LB-335: DHODH regulates transcriptional elongation during melanoma evolution: insights from zebrafish screening

Abstract Melanoma cells are derived from the neural crest, a transient, multipotent tissue present only during embryogenesis. Using zebrafish models, we aimed to determine whether these embryonic neural crest gene programs would make therapeutic targets in melanoma. Transgenic zebrafish expressing BRAFV600E under the mitf promoter develop melanoma when crossed with p53 mutants. From the earliest stages of transformation, and throughout overt tumorigenesis, these tumors express multiple embryonic neural crest progenitor markers such as SOX10, EDNRB and MITF. Human melanomas were similar: 50–75% expressed progenitor markers, but only 15% expressed the differentiation marker DCT. We performed a chemical genetic screen in zebrafish embryos to identify suppressors of the neural crest gene program to determine their therapeutic utility. Of 2000 small molecules, we found one class, inhibitors of the enzyme DHODH, that led to a complete abrogation of neural crest development during embryogenesis. Treated animals were essentially albino, devoid of all derivative melanocytes that eventually give rise to melanoma. Developmentally, DHODH suppression exerts this effect by blocking transcriptional elongation of genes such as MITF, in a manner dependent upon the elongation factor SUPT5H. In melanoma cells, we measured transcriptional elongation after DHODH inhibition via RNA pol II chromatin immunprecipitation coupled with massively parallel sequencing (ChIP-Seq). Similar to embryonic development, inhibiting DHODH leads to a defect in transcriptional elongation at select loci. We then tested whether leflunomide, a DHODH inhibitor approved for rheumatoid arthritis, could block melanoma growth. Either alone, or in combination with the BRAFV600E inhibitor PLX4032, leflunomide led to a dramatic decrease in melanoma growth in vitro and in vivo. These studies suggest that modulating the neural crest identity of melanoma cells is a distinct therapeutic avenue that is likely to cooperate with inhibiting oncogenic mutations such as BRAFV600E. We plan to extend this work into the clinical trial setting, highlighting the rapidity with which discoveries in zebrafish can be translated into the clinic. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr LB-335. doi:10.1158/1538-7445.AM2011-LB-335

Differential Expression of MicroRNAs in Tumors from Chronically Inflamed or Genetic (APCMin/+) Models of Colon Cancer

BackgroundChronic inflammation associated with ulcerative colitis predisposes individuals to increased colon cancer risk. The aim of these studies was to identify microRNAs that are aberrantly regulated during inflammation and may participate in transformation of colonic epithelial cells in the inflammatory setting.Methodology/Principal FindingsWe have use quantitative PCR arrays to compare microRNA (miRNA) expression in tumors and control colonic epithelial cells isolated from distal colons of chronically inflamed mice and APCMin/+ mice. Rank order statistics was utilized to identify differentially regulated miRNAs in tumors that arose due to chronic inflammation and/or to germline APC mutation. Eight high priority miRNAs were identified: miR-215, miR-137, miR-708, miR-31, and miR-135b were differentially expressed in APC tumors and miR-215, miR-133a, miR-467d, miR-218, miR-708, miR-31, and miR-135b in colitis-associated tumors. Four of these (miR-215, miR-708, miR-31, and miR-135b) were common to both tumors types, and dysregulation of these miRNAs was confirmed in an independent sample set. Target prediction and pathway analysis suggests that these microRNAs, in the aggregate, regulate signaling pathways related to MAPK, PI3K, WNT, and TGF-β, all of which are known to be involved in transformation.Conclusions/SignificanceWe conclude that these four miRNAs are dysregulated at some very early stage in transformation of colonic epithelial cells. This response is not dependent on the mechanism of initiation of transformation (inflammation versus germline mutation), suggesting that the miRNAs that we have identified are likely to regulate critical signaling pathways that are central to early events in transformation of colonic epithelial cells.

Loss of BRCA1 leads to an increase in epidermal growth factor receptor expression in mammary epithelial cells, and epidermal growth factor receptor inhibition prevents estrogen receptor-negative cancers in BRCA1-mutant mice

IntroductionWomen who carry a BRCA1 mutation typically develop "triple-negative" breast cancers (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor and Her2/neu. In contrast to ER-positive tumors, TNBCs frequently express high levels of epidermal growth factor receptor (EGFR). Previously, we found a disproportionate fraction of progenitor cells in BRCA1 mutation carriers with EGFR overexpression. Here we examine the role of EGFR in mammary epithelial cells (MECs) in the emergence of BRCA1-related tumors and as a potential target for the prevention of TNBC.MethodsCultures of MECs were used to examine EGFR protein levels and promoter activity in response to BRCA1 suppression with inhibitory RNA. EGFR was assessed by immunoblot and immunofluorescence analysis, real-time reverse transcriptase-polymerase chain reaction assay (RT-PCR) and flow cytometry. Binding of epidermal growth factor (EGF) to subpopulations of MECs was examined by Scatchard analysis. The responsiveness of MECs to the EGFR inhibitor erlotinib was assessed in vitro in three-dimensional cultures and in vivo. Mouse mammary tumor virus-Cre recombinase (MMTV-Cre) BRCA1flox/flox p53+/- mice were treated daily with erlotinib or vehicle control, and breast cancer-free survival was analyzed using the Kaplan-Meier method.ResultsInhibition of BRCA1 in MECs led to upregulation of EGFR with an inverse correlation of BRCA1 with cellular EGFR protein levels (r2 = 0.87) and to an increase in cell surface-expressed EGFR. EGFR upregulation in response to BRCA1 suppression was mediated by transcriptional and posttranslational mechanisms. Aldehyde dehydrogenase 1 (ALDH1)-positive MECs expressed higher levels of EGFR than ALDH1-negative MECs and were expanded two- to threefold in the BRCA1-inhibited MEC population. All MECs were exquisitely sensitive to EGFR inhibition with erlotinib in vitro. EGFR inhibition in MMTV-Cre BRCA1flox/flox p53+/- female mice starting at age 3 months increased disease-free survival from 256 days in the controls to 365 days in the erlotinib-treated cohort.ConclusionsWe propose that even partial loss of BRCA1 leads to an overall increase in EGFR expression in MECs and to an expansion of the highly EGFR-expressing, ALDH1-positive fraction. Increased EGFR expression may confer a growth advantage to MECs with loss of BRCA1 at the earliest stages of transformation. Employing EGFR inhibition with erlotinib specifically at this premalignant stage was effective in decreasing the incidence of ER-negative breast tumors in this mouse model.

Quantitative comparison of the phase-transformation kinetics in a sharp-interface and a phase-field model

A sharp-interface model, which provides an accurate description of diffusional phase-transformation kinetics [C. Bos, J. Sietsma, Scripta Mater. 57 (2007) 1085–1088], is used to evaluate the transformation kinetics as calculated by a diffuse-interface multi-phase-field model, in particular the effect of the interface thickness will be investigated. This is done for the isothermal austenite-to-ferrite transformation in a C–Mn steel, using the simple geometry of a single ferrite grain growing in the bulk of the austenite matrix. For the sake of computation time, this analysis is limited to one- and two-dimensional space, although it can be extended to three-dimensional space straightforwardly. Small deviations of the numerical phase-field profile from the analytical stationary solution, used to match the phase-field equation to the equation for the sharp-interface kinetics, results in a lower effective interface mobility compared to the input value. This deviation, more pronounced in the early stage of transformation, can be minimised by reducing the grid size, while keeping the number of interface grid points constant. During stationary growth, a good agreement was found between phase-field and sharp-interface solution, although a small deviation of about 7% still remains if six grid points are chosen for the interface width. This deviation could not be reduced further by a better grid resolution, but can be overcome by a higher number of grid points within the diffuse interface.

Expression of junB is markedly stimulated by glycyrrhizin in a human hepatoma cell line

Effective therapeutic approaches for liver cancer are expected to be the prevention of chronic inflammation, progression of chronic liver injury to liver cancer and/or tumor cell growth by activating various oncogenes. Activation of the c-jun oncogene occurs in many cases at the early stage of transformation of chronic hepatitis into liver cancer. Accordingly, inhibition of c-jun gene function is thought to be important for the therapy of liver cancer. Although the junB gene has been identified as a c-jun-related gene, it acts as a tumor suppressor gene through competitive binding of JUNB with c-JUN. Therefore, alteration in junB gene expression in chronic hepatitis or liver cancer is an interesting target for the development of both therapeutic treatment and medicines. Monoammonium glycyrrhizinate (MAG) is used for the treatment of viral hepatitis or the prevention of chronic liver diseases. However, the mechanism by which MAG is involved in the suppression of oncogene function has not yet been characterized. In the present study, we first found that MAG highly stimulated JUNB expression in a human hepatoma cell line, HepG2. We examined the mechanism by which MAG increases junB gene expression by considering the previously published effects of MAG on the onset or development of chronic hepatitis or liver injury. The present data suggest that marked activation of junB expression leads to a pivotal role for MAG in multiple medical applications.

EGF and TGF-1 Effects on Thyroid Function

Normal epithelial thyroid cells in culture are inhibited by TGF-β1. Instead, transformed thyroid cell lines are frequently resistant to its growth inhibitory effect. Loss of TGF-β responsiveness could be due to a reduced expression of TGF-β receptors, as shown in transformed rat thyroid cell lines and in human thyroid tumors, or to alterations of other genes controlling TGF-β signal transduction pathway. However, in thyroid neoplasia, a complex pattern of alterations occurring during transformation and progression has been identified. Functionally, TGF-β1 acts as a tumor suppressor in the early stage of transformation or as a tumor promoter in advanced cancer. This peculiar pleiotropic behaviour of TGF-β may result from cross-talk with signalling pathways mediated by other growth factors, among which EGF-like ligands play an important role. This paper reports evidences on TGF-β1 and EGF systems in thyroid tumors and on the cross-talk between these growth factors in thyroid cancer.

Carbon supersaturation of ferrite in a nanocrystalline bainitic steel

The extremely slow transformation kinetics of a nanocrystalline bainitic steel allows the carbon content of the bainitic ferrite away from any carbon-enriched regions such as dislocations and boundaries to be determined by atom probe tomography as the bainite transformation progresses at 200 °C. A high level of carbon, well above that expected from para-equilibrium with austenite, has been detected in solid solution in bainitic ferrite at the early stage of transformation. Results provide strong evidence that bainite transformation is essentially displacive in nature so that the newly formed bainitic ferrite retains much of the carbon content of the parent austenite.

<i>In Situ</i> High Temperature X-Ray Studies on Bainitic Transformation of Austempered Silicon Alloyed Steels

The in-situ X-ray diffraction observations of the bainitic transformation of silicon alloyed steels were performed using the high temperature X-ray diffraction technique. The experimental results have shown that the volume fraction and carbon content of austenite remains a constant value which indicate that the transformation is almost finished after the early stages of austempering transformation. Asymmetry diffraction peaks are obtained for samples at the early stage of transformation due to a heterogeneous distribution of carbon in different regions of austenite and thus exists two types of austenite: low-carbon austenite (γLC) and the high-carbon austenite (γHC). The experimental results supports that the bainite growth is by a non-diffusive mechanism when austempering temperature is in the lower bainite transformation temperature.

BCR/ABL Requires Fanconi Anemia D2 (FANCD2) Protein to Transform Hematopoetic Stem Cells.

Abstract 3249Poster Board III-1Fanconi D2 protein (FANCD2) is monoubiquitinated on K561 (FANCD2-Ub) and phosphorylated on S222 (FANCD2-phosphoS222) in response to DNA double-strand breaks (DSBs). FANCD2-Ub interacts with RAD51 to facilitate homologous recombination repair (HRR), and FANCD2-phosphoS222 activates the S phase checkpoint. We detected an increased amount of FANCD2-Ub in CD34+ chronic myeloid leukemia (CML) stem/progenitor cells from chronic phase (CML-CP) and blast crisis (CML-BC) patients and in BCR/ABL-positive cell lines in comparison to normal counterparts. This effect was not associated with up-regulation of FANCD2 ubiquitinase FANCL or down-regulation of FANCD2 deubiquitinase USP1, but was reversed after inhibition of BCR/ABL kinase with imatinib and reduction of reactive oxygen species (ROS) with antioxidant vitamin E (VE) or N-acetylcysteine (NAC). In addition mitomycin C routinely used for diagnostic testing in Fanconi anemia, strongly elevated FANCD2-Ub in CD34+ CML cells. Therefore we postulate that FANCD2-Ub may play a role in BCR/ABL transformation. In support for this hypothesis, we observed that clonogenic potential of BCR/ABL-positive murine leukemia stem cells (LSCs)-enriched FANCD2-/- Sca1+Kit+lin- bone marrow cells was reduced by approximately 10-fold in comparison to BCR/ABL-positive FANCD2+/+ counterparts; non-transformed -/- and +/+ cells displayed similar clonogenic potential stimulated by SCF and GM-CSF. Restoration of FANCD2 expression “rescued” the impaired clonogenic activity of BCR/ABL-positive FANCD2-/- cells. In addition, expression of BCR/ABL kinase, but not the kinase-deficient K1172R mutant, inhibited the proliferation rate of FANCD2-/- human lymphoblast cell line. Negative effect of BCR/ABL kinase on FANCD2-/- cell growth was reversed by expression of exogenous FANCD2. The in vitro growth defect of BCR/ABL-positive FANCD2-/- cells was accompanied by delayed leukemogenesis in SCID mice. These results suggest that FANCD2, a key regulator of DNA damage response, may play an important role in the initiation and/or maintenance of BCR/ABL-positive leukemias. We showed before that CD34+ CML-CP and CML-BC cells contain higher number of ROS-induced DSBs in comparison to CD34+ cells from healthy donors [Cancer Res., 2008]. Recent studies also revealed that LSC-enriched (CD34+CD38-) CML-CP and CML-BC cells display more DSBs than normal counterparts. Thus, BCR/ABL-mediated leukemogenesis is associated with accumulation of an excess of ROS-induced DSBs, which if not repaired, may induce apoptosis. We hypothesize that FANCD2 is necessary to “protect” leukemia cells from potentially lethal effect of BCR/ABL-induced oxidative DNA damage (including DSBs) at early stages of transformation and possibly also during the progression to CML-BC. This suggestion is supported by the observation that BCR/ABL-positive FANCD2-/- cells accumulate more DSBs in comparison to +/+ counterparts. This effect did not cause any significant changes in cell cycle distribution, but resulted in discrete but persistent apoptosis. Scavenging of ROS by VE and NAC reduced the number of DSBs and eliminated the growth defect of BCR/ABL-positive FANCD2-/- cells. Accumulation of excessive DNA damage (DSBs) and impairment of growth potential of BCR/ABL-positive FANCD2-/- cells could be prevented by expression of FANCD2 wild-type (proficient in DNA repair and S phase checkpoint) and S222A phosphorylation-deficient mutant (proficient in DNA repair, but deficient in S phase checkpoint), but not the K561R monoubiquitination-deficient mutant (deficient in DNA damage, but proficient in S phase checkpoint). Since FANCD2-Ub interacts with RAD51 to promote HRR and BCR/ABL employs RAD51-dependent HRR to repair numerous DSBs induced by ROS, it is plausible that elevated expression of FANCD2-Ub may facilitate DSB repair to protect leukemia cells from lethal effects of DSBs. In concordance, co-localization of FANCD2-Ub and RAD51 was readily detected in the nuclei of BCR/ABL-positive leukemia cells. In conclusion our results indicate that FANCD2 plays an important role during the induction and perhaps also progression of Philadelphia-chromosome positive leukemias due to its ability to facilitate the repair of numerous, potentially lethal DSBs. Disclosures:No relevant conflicts of interest to declare.

Editorial: Lines of Communication

Changes in library and information professional communications and journal publication in the last two decades are considered. Journals of professional bodies such as the Library Association and Aslib have now been sold to commercial publishers. The emergence of electronic journals is exemplified. Electronic discussion lists and newer forms of interactive communication, e.g. blogs and social networking sites, are discussed. The time spent in accessing and using e-sources of professional information should lead to improved services to users. Professional lines of communication are at an early stage of transformation, the progress of which needs analysis and description.

Bainite Structures and Mechanical Properties of SUP12 Spring Steel

The strength of spring steels has been increasing in order to cope with the demands of lightweightness in automobile applications. However, high strength steels, typically consisting of tempered martensite structures, accompanied by large reduction of toughness are susceptible to failure of spring properties such as fatigue resistance in corrosive conditions, because of increase in notch sensitivity. Since bainite often exhibits high strength and toughness in comparison with tempered martensite, we have studied microstructures and mechanical properties of an austempered spring steel (JIS-SUP12) by means of scanning electron microscopy and tensile tests in order to examine the potential application of bainitic spring steels. The result shows that carbide-free and lath-like bainitic ferrite was formed at austempering temperatures higher than 400°C, while plate-like bainitic ferrite with fine carbide precipitations was formed at temperatures lower than 300°C. The fraction of the bainitic ferrite increased whereas that of the martensite decreased with increased holding time in austempering. The amount of the retained austenite increased during the early stage of transformation and then decreased with further holding. At optimum austempering condition, the bainite with high strength, high elongation and reduction of area superior to tempered martensite was obtained.

In situ x-ray observation of bainitic transformation of austempered silicon alloyed steel

The in situ x-ray diffraction observations of the bainitic transformation were conducted by using the high-temperature x-ray diffraction technique. The volume fraction and carbon content of austenite depend on the transformation temperature. The d{110} value of bainitic ferrite decreases with increasing austempering temperature, which is related to the decrease of carbon concentration in bainitic ferrite. Asymmetry diffraction peaks are obtained for samples at the early stage of transformation at any austempering temperatures. This asymmetry diffraction peak after the formation of bainitic ferrite could be attributed to a heterogeneous distribution of carbon in different regions of austenite and show that two types of austenite with different carbon contents, low-carbon austenite (γLC) and the high-carbon austenite (γHC), exist during the transformation. The microstructure after cooling down to room temperature is presented to show the effectiveness of the x-ray diffraction analysis.

In-Situ High Temperature X-ray Studies of Austempering Transformation in High Silicon Cast Steel

The in-situ X-ray diffraction observations of the bainitic transformation of high silicon cast steel were performed using the high temperature X-ray diffraction technique. The volume fraction and carbon content of austenite depend on the transformation temperature. The experimental result has shown that the volume fraction of austenite ceases to a constant value which indicate that the transformation is almost finished after holding for about 1000 s. Asymmetry diffraction peaks are obtained for samples at the early stage of transformation due to a heterogeneous distribution of carbon in different regions of austenite and thus exists two types of austenite: low-carbon austenite (γLC) and the high-carbon austenite (γHC). The volume fraction of bulk austenite with low carbon decreases greatly at the early stage of transformation and then tends towards zero. The lattice parameter of both low-carbon and high-carbon austenite increases with the holding time due to the carbon partition from the supersaturated ferrite to the austenite. The experimental results supports that the bainite growth is by a diffusionless mechanism when austempering temperature is in the lower bainite transformation temperature range.

Claudin-1 and claudin-2 expression is elevated in inflammatory bowel disease and may contribute to early neoplastic transformation

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal adenocarcinoma. The factors that result in IBD-associated carcinogenesis are not understood. We hypothesized that altered expression of intestinal epithelial tight junction proteins might contribute to neoplastic progression. Semiquantitative immunohistochemical staining of human biopsies was used to assess expression of the tight junction proteins claudin-1, claudin-2, claudin-4, and occludin in IBD, IBD-associated dysplasia, acute, self-limited colitis (ASLC), and sporadic adenomas. Claudin-1 and claudin-2 expression was elevated in active IBD, adenomas, and IBD-associated dysplasia, but not ASLC. In contrast, claudin-4 expression was elevated in both active IBD and ASLC. Occludin expression was similar to control in all cases. Importantly, in IBD, claudin-1 and claudin-2 expression correlated positively with inflammatory activity. To investigate mechanisms underlying altered claudin expression, β-catenin activation was assessed as nuclear localization. Like claudin-1 and claudin-2, β-catenin was markedly activated in IBD, sporadic dysplasia, and IBD-associated dysplasia, but was only slightly activated in ASLC. Taken together, these data suggest that β-catenin transcriptional activity is elevated in chronic injury and that this may contribute to increased claudin-1 and claudin-2 expression. We speculate that increased claudin-1 and claudin-2 expression may be involved at early stages of transformation in IBD-associated neoplasia.