Numerical modeling for RF and microwave heating using FE comes of age.

This paper gives a brief resume of the numerical work carried out over the past decade at the Electricity Utilisation Group usingfinite elements for the characterization of RF and microwave heating systems. Maxwell's equations are solved in 3D while for coronas the Poisson's and particle continuity equations are solved in 2D. In addition work on modeling thin films and the use of parallel computing describes the latest work to emanate from the group.

Application of the resistive sheet in finite element microwave heating systems.

The use of the resistive sheet for characterizing thin metallic films is presented in a microwave heating context. A finite edge element formulation is used to include the resistive sheet surface integral in both the frequency and time domains. The properties of the resistive sheet are compared with analytical expressions for the reflection, transmission and absorption coefficients and a correction factor is suggested to improve the accuracy of the numerical implementation. Results are presented for single and multimode systems.

Acute pancreatitis results in induction of heat shock proteins 70 and 27 and heat shock factor-1.

Heat shock proteins (HSPs) 70 and 27 are stress-responsive proteins that are important for cell survival after injury; the expression of these HSPs is regulated primarily by the transcription factor heat shock factor-1 (HSF-1). The purpose of this study was to determine the effect of acute pancreatitis on pancreatic HSPs (70, 27, 60, and 90) expression and to assess potential mechanisms for HSP induction using a murine model of cerulein-induced pancreatitis. We found an increase of both HSP70 and HSP27 levels with expression noted throughout the pancreas after induction of pancreatitis. HSP60 and HSP90 levels were constitutively expressed in the pancreas and did not significantly change with acute pancreatitis. HSF-1 DNA binding activity increased in accordance with increased HSP expression. We conclude that acute pancreatitis results in a marked increase in the expression of HSP70 and HSP27. Furthermore, the induction of HSP70 and HSP27 expression was associated with a concomitant increase in HSF-1 binding activity. The increased expression of both HSP70 and HSP27 noted with pancreatic inflammation may confer a protective effect for the remaining acini after acute pancreatitis.

Gut peptide receptor expression in human pancreatic cancers.

OBJECTIVE: To determine the prevalence of gastrointestinal (GI) peptide receptor expression in pancreatic cancers, and to further assess signaling mechanisms regulating neurotensin (NT)-mediated pancreatic cancer growth. SUMMARY BACKGROUND DATA: Pancreatic cancer remains one of the leading causes of GI cancer death; novel strategies for the early detection and treatment of these cancers is required. Previously, the authors have shown that NT, an important GI hormone, stimulates the proliferation of an NT receptor (NTR)-positive pancreatic cancer. METHODS: A total of 26 human pancreatic adenocarcinomas, obtained after resection, and 5 pancreatic cancer xenografts were analyzed for expression of NTR, vasoactive intestinal peptide receptor (VIPR), substance P receptor (SPR), and gastrin-releasing peptide receptor (GRPR). In addition, NTR expression, [Ca2+]i mobilization, and growth in response to NT was determined in L3.6, a metastatic pancreatic cancer cell line. RESULTS: Neurotensin receptor was expressed in 88% of the surgical specimens examined and all five of the pancreatic cancer xenografts. In contrast, VIPR, SPR, and GRPR expression was detected in 31%, 27%, and 8% of pancreatic cancers examined, respectively. Expression of NTR, functionally coupled to the Ca2+ signaling pathway, was identified in L3.6 cells; treatment with NT (10 micromol/L) stimulated proliferation of these cells. CONCLUSIONS: The authors demonstrated NTR expression in most of the pancreatic adenocarcinomas examined. In contrast, VIPR, SPR, and GRPR expression was detected in fewer of the pancreatic cancers. The expression of NTR and other peptide receptors suggests the potential role of endocrine manipulation in the treatment of these cancers. Further, the presence of GI receptors may provide for targeted chemotherapy or radiation therapy or in vivo scintigraphy for early detection.

Downregulation of mitogen-activated protein kinases in human colon cancers.

BACKGROUND: Activation of the mitogen-activated protein kinases (MAPKs) appears to play an important role in both proliferation and transformation of various cells; the role of MAPK activation in colorectal cancers has not been clearly defined. The purpose of our study was to determine whether MAPK activity and protein levels were increased in colorectal cancers. METHODS: Colorectal cancers and adjacent normal mucosa from 21 patients were extracted for protein. Expression levels and activity of the MAPKs (ERK1/2, JNK1, p38 and ERK3) were assessed by immunoblot analysis and in vitro kinase assays, respectively. In addition, changes in myelin basic protein (MBP) kinase activity and autophosphorylation were determined by in-gel kinase assays. RESULTS: The activities of ERK1/2, JNK1 and p38 were downregulated in the majority of cancers; ERK3 kinase activity was increased in 10 of 21 cancers. The presence of proteins displaying increased MBP phosphorylation and autophosphorylation was identified specifically in the cancers by in-gel kinase assays. CONCLUSIONS: Our findings demonstrate that the constitutive activation of ERK1/2, JNK1 and p38 is not a feature of colorectal cancers. Moreover, our in-gel kinase results suggest that protein kinases, other than the MAPKs assessed, may play a more crucial role in colon carcinogenesis.

Neurotensin-mediated activation of MAPK pathways and AP-1 binding in the human pancreatic cancer cell line, MIA PaCa-2.

Neurotensin (NT), a gastrointestinal (GI) hormone, binds its receptor (NTR) to stimulate proliferation of normal and neoplastic GI tissues; the molecular mechanisms remain largely undefined. Mitogen-activated protein kinases (MAPKs) are a family of intracellular kinases that transmit mitogenic signals by translocating to the nucleus and activating transcription factors. The purposes of this study were: (1) to identify whether the MAPKs (ERK1/2 and JNK) are activated by NT and (2) to determine the effect of NT on downstream transcription factors using the human pancreatic adenocarcinoma cell line, MIA PaCa-2, which possesses high-affinity NTR. Both ERK and JNK activity were stimulated within 3-6 min by treatment with NT (10 nM); steady-state levels of ERK and JNK protein were unchanged. Moreover, NT treatment resulted in increased AP-1 binding activity as determined by gel shift analysis. Delineating the signal transduction mechanisms regulating the cellular effects of NT will provide important insights into the molecular pathways responsible for NT-mediated effects on both normal and neoplastic cells.

The effect of wall losses in the numerical simulation of microwave heating problems.

A study is made into the numerical modeling of wall losses for a microwave heating application. It makes use of a surface integral term for both a frequency and time domain finite edge element formulation in order to model the wall impedance of the enclosed microwave cavity. The paper describes how the surface element matrix of the complex wall impedance is combined with the matrix formulation. The results are checked against analytical expressions for a single mode resonant cavity. An analysis on the effect of lossy walls is provided using four low-loss material insertions over a range of surface conductivities.

Mitochondrial DNA damage and altered membrane potential (delta psi) in pancreatic acinar cells induced by reactive oxygen species.

BACKGROUND: Reactive oxygen species (ROS) have been implicated in the induction of acute pancreatitis. Mitochondria possess a distinct genome (mtDNA) that is more susceptible to ROS-induced damage than nuclear DNA (nDNA). The purpose of our study was to determine the effect of ROS on mitochondrial function and membrane potential (delta psi mt), to identify signal transduction mechanisms activated by ROS, and to quantify damage to mtDNA in an in vitro pancreatitis model. METHODS: Pancreatic acinar cells, AR4-2J, were treated with saline solution (control) or hydrogen peroxide (H2O2), a representative ROS. Mitochondrial function was assessed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; to determine delta psi mt, rhodamine-123 uptake was measured. Intracellular calcium levels and c-Jun N-terminal kinase activity was determined; gel mobility shift assays were performed to assess induction of the transcription factor NF-kappa B. To quantitate DNA damage, a novel polymerase chain reaction-based procedure was performed. RESULTS: Mitochondrial function and delta psi mt were significantly decreased with oxidative damage. H2O2 treatment resulted in increased intracellular calcium levels, activation of c-Jun N-terminal kinase, and induction of NF-kappa B DNA binding. Treatment of AR4-2J cells with H2O2 resulted in selective mtDNA damage; nDNA was not affected. CONCLUSIONS: Our data demonstrate that pancreatic mtDNA is more susceptible to oxidative damage than nDNA; this damage is associated with decreases in mitochondrial function and delta psi mt and activation of downstream signal transduction pathways. Mitochondrial damage mediated by ROS may play a central role in pancreatic cell injury associated with acute pancreatitis.

Signal transduction mechanisms in neurotensin-mediated cellular regulation.

BACKGROUND: Neurotensin, an important gut hormone, binds its receptor (NTR) to stimulate proliferation of intestinal cells; the molecular mechanisms remain largely undefined. Mitogen-activated protein kinases (MAPKs) translocate to the nucleus and induce transcription factors (eg, c-Fos) in response to certain trophic agents. The purpose of this study was (1) to define the signaling mechanisms regulating neurotensin and (2) to determine whether the AP-1 transcription factor c-Fos is induced. METHODS: Expression of the NTR gene was determined in the human colon cancer cell lines KM12C, KML4A, and KM20 by Northern blot analysis and ribonuclease-protection experiments. To assess whether NTR was functionally coupled to the CA(2+)-signaling pathway, intracellular CA2+ ([Ca2+]i) mobilization was assessed by fura-2 spectrofluorometry. To determine whether the MAPK signaling pathway was activated in KM20 cells by neurotensin, Western blots for the phosphorylated forms of MAPK (p42 and p44) and in vitro kinase assays were performed. In addition, Western blots were performed to assess levels of c-Fos after neurotensin treatment. RESULTS: The NTR gene was expressed in the KM20 cell line but not in KM12C or KM12LA. The NTR in KM20 cells was functionally coupled to the CA(2+)-signaling pathway as noted by a rapid (30 seconds) mobilization of [Ca2+]i after addition of neurotensin; the neurotensin-mediated response was blocked by the NTR antagonist SR48692. Both p42MAPK and p44MAPK were stimulated by neurotensin approximately 3 to 6 minutes after treatment. Increased levels of c-Fos were demonstrated, with peak levels occurring 2 hours after addition of neurotensin. CONCLUSIONS: Our results demonstrate that neurotensin binds to its endogenous NTR in KM20 cells with stimulation of the Ca(2+)- and MAPK-signaling pathways and an increase in the levels of the AP-1 protein c-Fos. Delineating the signal transduction mechanisms regulating the cellular effects of neurotensin will provide important insights into the molecular pathways responsible for gut hormone-mediated proliferation.