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Pancreatic intraepithelial neoplasia (PanIN) is the most common precursor lesion of pancreatic ductal adenocarcinoma (PDAC), which has poor prognosis with a short median overall survival of 6-12 months and a low 5-year survival rate of approximately 3%. It is crucial to remove PanIN lesions to prevent the development of invasive PDAC, as PDAC spreads rapidly outside the pancreas. This review aims to provide the latest knowledge on PanIN risk, pathology, cellular origin, genetic susceptibility, and diagnosis, while identifying research gaps that require further investigation in this understudied area of precancerous lesions. PanINs are classified into PanIN 1, PanIN 2, and PanIN 3, with PanIN 3 having the highest likelihood of developing into invasive PDAC. Differentiating between PanIN 2 and PanIN 3 is clinically significant. Genetic alterations found in PDAC are also present in PanIN and increase with the grade of PanIN. Imaging methods alone are insufficient for distinguishing PanIN, necessitating the use of genetic and molecular tests for identification. In addition, metabolomics technologies and miRNAs are playing an increasingly important role in the field of cancer diagnosis, offering more possibilities for efficient identification of PanIN. Although detecting and stratifying the risk of PanIN poses challenges, the combined utilization of imaging, genetics, and metabolomics holds promise for improving patient survival in this field. [ABSTRACT FROM AUTHOR]

Expansion-break connecting rods are high-end products for automotive precision transmission. They need to have high strength, high toughness, and brittle cleavage fracture characteristics during cracking processing. Continuous casting production of nonquenched and tempered steel for high-carbon, sulfur-containing, free-cutting, and expanding connecting rods is the current trend for efficient production. Based on the typical bloom continuous casting process and analysis of the as-cast structure and composition uniformity, the common unqualified fracture morphology due to as-cast hereditary factors were studied. Taking the typical German C70S6 steel as an example, a 250 mm × 280 mm section-curved continuous caster was adopted to study the as-cast macrostructure and dendrite morphology of the bloom casting with popular mold electromagnetic stirring. Moreover, the chemical distribution at different crystal regions was studied. Results show that the common center shrinkage defects of high-carbon steel continuous casting blooms are under control, which are beneficial to improve the qualified rate of internal flaw detection for their subsequent hot-rolled bars. However, it is found that there are obvious negative segregation white bands of carbon and sulfur and the deflection of columnar crystals in the solidification front of the initial solidified shell. Both the image analysis of the metallographic sample and solidification simulation by a phase-field method show that this columnar crystal has countercurrent growth characteristics. In addition, its deflection angle is the result of the primary dendrite tip growing in the opposite direction to the swirling fluid flow. In the center of the narrow surface, the measured primary dendrite deflection angle of the columnar crystal region is between −7° and 27°. EDS was used to further detect the distribution of the main alloying elements Si, Mn, and Mo in the different crystal regions of the bloom casting, revealing the segregation characteristics of the as-cast product and differences of each solute element. Finally, the heredity of this as-cast structure and composition segregation on the structure of subsequent hot-rolled bars and connecting rods was discussed. Moreover, the influence of the fracture inconsistency of its expansion and fracture processing were explored. It is pointed out that the as-cast quality control from the very beginning of casting has special significance in meeting the requirement of both processing and service properties of these high-grade high strength low alloy steels.

Owing to the large cross-section and wide solidification-temperature zone, bloom castings of medium- and high-carbon steels are prone to severe central shrinkage and macrosegregation defects. Flow control technologies such as nozzle injection mode and electromagnetic stirring, together with the casting speed, play a key role in the as-cast macrostructure and macrosegregation distribution in bloom castings achieving soundness and compositional homogeneity of the final as-rolled products. Based on the production process of a medium-carbon-steel bloom casting and its heavy section bars, various flow control modes have been adopted in the casting production to study their effects on the semiproduct solidification structure and the carbon distribution across the bloom section and the following rolled bars. The conventional nozzle with a single straight port shows that the equiaxed crystal ratio in the casting process can only increase from 6.06% to 11.71% with the M-EMS intensity changes from 0 to 800 A, in which a shrinkage cavity and macrosegregation exist along the centerline on the strand casting. While the novel five-port nozzle has been adopted, the equiaxed crystal ratio can reach 23.1% even with the M-EMS power off, and the center cavity index drops down to grade 1.0 or below, meeting the requirement of microvoid flaw detection for the bar products. Additionally, the carbon segregation across the bloom cross-section is observed to resemble an M-shaped curve with a maximum carbon segregation index in the columnar to equiaxed transition zone instead of the popular center region. For the heavy section bars rolled from bloom casting, a similar carbon distribution pattern as the cast is observed after hot working but with an even higher centerline segregation index. Therefore, considering the special quality requirements for the subsequent hot processing, the macrostructure and pattern and intensity of macro-segregation should be regulated from the beginning of casting with a reasonable flow control mode as mentioned in the study.

A three-dimensional numerical model combining electromagnetic field, fluid flow, heat transfer, and solidification has been established to study the effect of nozzle injection mode and mold electromagnetic stirring (M-EMS) on the internal quality of a continuously cast bloom. The model is validated by measured data of the magnetic flux density along the stirrer center line. According to the simulation and experimental results, M-EMS can introduce a horizontal swirling flow ahead of the solidification front, promoting the superheat dissipation of molten steel and columnar to equiaxed transition (CET). As the stirring current increases from 0 to 800 A, the superheat at the mold exit in the bloom center decreases by 1.9 K for the single-port nozzle case and 3.8 K for the five-port nozzle case. The resulting increase in the equiaxed crystal ratio is about 5.65% and 4.06%, respectively. In comparison, the injection mode shows a more significant influence on the heat transfer and solidification structure in the bloom under the present casting conditions. The superheat at the mold exit in the bloom center decreases by 5.1−7.7 K as the injection mode changes from a single-port nozzle to a five-port nozzle, and the increase in the equiaxed crystal ratio ranges between 14.8% and 17%. It is found that the flow velocity of the molten steel in front of the solidification interface for the five-port nozzle is higher than that for the single-port nozzle regardless of the M-EMS power. The washing effect here reinforces both the heat exchange through the solidification interface and the dendrite re-melting or fragmenting, stimulating the formation of an equiaxed crystal at the bloom center. In addition, it is observed that both the central shrinkage and carbon segregation have decreased with the five-port nozzle plus M-EMS. This suggests that the combined application of a five-port nozzle and M-EMS can effectively improve the internal quality of large bloom castings.

The emergence and widespread availability of network computing have made it possible for many computationally intensive applications to take advantage of distributing processing techniques at almost no additional cost. In this paper, we present a successful implementation of distributed processing for screening all possible single contingencies in an electric network model. The implementation is based on the remote execution model that is available in most UNIX based workstations. Our testing results show that near ideal speedups can be achieved for the contingency screening applications. Keywords: Distributed Processing, Contingency Screening, Security Analysis, Energy Management Systems

This paper presents the development and implementation of an Artificial Neural Network (ANN) based short-term system load forecasting model for the Energy Control Center of the Pacific Gas & Electric Company (PG&E). Insights gained during the development of the model regarding the choice of the input variables and their transformations, the design of the ANN structure, the selection of the training cases and the training process itself will be described in the paper. Attention was paid to model accurately special events, such as holidays, heat-waves, cold snaps and other conditions that disturb the normal pattern of the load. The significant impact of special events on the model's performance was established through testing of an existing load forecasting package that is currently in production use. The new model has been tested under a wide variety of conditions and it is shown in this paper to produce excellent results. Comparison results between the existing, regression based model and the ANN model are very encouraging. The ANN model consistently outperforms the existing model in terms of both, average errors over a long period of time and number of 'large' errors. The ANN model has also been integrated with PG&E's Energy Management System (EMS). It is envisioned that the ANN model will eventually substitute the existing model to support the Company's real-time operations. In the interim both models will be available for production use. Keywords: System Load Forecasting, Artificial Neural Network Technology, Training, Regression Analysis.

Abstract Background Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells. Methods RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes. Results Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes. Conclusions Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.

Abstract Background Abberant aryl hydrocarbon receptor (AhR) expression and AhR pathway activation are involved in gastric carcinogenesis. However, the relationship between AhR pathway activation and gastric cancer progression is still unclear. In present study, we used 2,3,7,8-tetrachlorodibenzo-para-dioxin (TCDD), a classic and most potent ligand of AhR, to activate AhR pathway and investigated the effect of AhR pathway activation on human gastric cancer AGS cell invasion and explored the corresponding mechanism. Results To determine whether AhR pathway can be activated in AGS cells, we examined the expression of CYP1A1, a classic target gene of AhR pathway, following TCDD exposure. RT-PCR and western blot analysis showed that both CYP1A1 mRNA and protein expression were increased in a dose-dependent manner following TCDD treatment and AhR antagonist resveratrol (RSV) could reverse this TCDD-induced CYP1A1 expression. To determine whether TCDD treatment of AGS cells results in an induction of MMP-9 expression, we detected MMP-9 mRNA using RT-PCR and detected MMP-9 enzymatic activity using gelatin zymography. The results showed that both MMP-9 mRNA expression and enzymatic activity were gradually increased with the concentration increase of TCDD in media and these changes could be reversed by RSV treatment in a dose-dependent manner. To examine whether AhR activation-induced MMP-9 expression and activity in AGS cells results in increased migration and invasion, we performed wound healing migration assay and transwell migration and invasion assay. After TCDD treatment, the migration distance and the migration and invasion abilities of AGS cells were increased with a dose-dependent manner. To demonstrate AhR activation-induced MMP-9 expression is mediated by c-Jun, siRNA transfection was performed to silence c-Jun mRNA in AGS cells. The results showed that MMP-9 mRNA expression and activity in untreated control AGS cells were very weak; After TCDD (10 nmol/L) treatment, MMP-9 mRNA expression and activity were significant increased; This TCDD-induced MMP-9 expression and activity increase could be abolished by c-Jun siRNA transfection. Conclusion AhR pathway activation enhances gastric cancer cell invasiveness likely through a c-Jun-dependent induction of MMP-9. Our results provide insight into the mechanism and function of the AhR pathway and its impact on gastric cancer progression.