Automatic programming of simulation models

The objective of automatic programming is to improve the overall environment for describing the program. This improved environment is realized by a reduction in the amount of detail that the programmer needs to know and is exposed to. Furthermore, this improved environment is achieved by a specification language that is more natural to the user's problem domain and to the user's way of thinking and looking at the problem. The goal of this research is to apply the concepts of automatic programming (AP) to modeling discrete event simulation system. Specific emphasis is on the design and development of simulation tools to assist the modeler define or construct a model of the system and to then automatically write the corresponding simulation code in the target simulation language, GPSS/PC. A related goal is to evaluate the feasibility of various languages for constructing automatic programming simulation tools

Automatic programming of simulation models

The concepts of software engineering were used to improve the simulation modeling environment. Emphasis was placed on the application of an element of rapid prototyping, or automatic programming, to assist the modeler define the problem specification. Then, once the problem specification has been defined, an automatic code generator is used to write the simulation code. The following two domains were selected for evaluating the concepts of software engineering for discrete event simulation: manufacturing domain and a spacecraft countdown network sequence. The specific tasks were to: (1) define the software requirements for a graphical user interface to the Automatic Manufacturing Programming System (AMPS) system; (2) develop a graphical user interface for AMPS; and (3) compare the AMPS graphical interface with the AMPS interactive user interface

The Potential Utility of Curcumin in the Treatment of HER-2-Overexpressed Breast Cancer: An In Vitro and In Vivo Comparison Study with Herceptin

HER-2 is an important oncoprotein overexpressed in about 15–25% of breast cancers. We hypothesized that the ability of curcumin to downregulate HER-2 oncoprotein and inhibit the signal transduction pathway of PI3K/Akt, MAPK, and NF-κB activation may be important in the treatment of HER-2-overexpressed breast cancer. To examine the effect of curcumin on breast cancer cells, MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr (a herceptin resistant strain from SK-BR-3) cells were used for in vitro analysis. The in vivo effect of curcumin on HER-2-overexpressed breast cancer was investigated with the HER-2-overexpressed BT-474 xenograft model. Cell growth, cell cycle change, the antimobility effect, signal transduction, and xenograft volume analysis between groups treated with herceptin and/or curcumin were tested. Curcumin decreased the cell growth of various breast cancer cell lines (MCF-7, MDA-MB-231, MCF-10A, BT-474, and SK-BR-3-hr). In Western blot analysis, the phosphorylation of Akt, MAPK, and expression of NF-κB were reduced in BT-474 cells, but not in SK-BR-3-hr cells, after treatment with herceptin. When treated with curcumin, the HER-2 oncoprotein, phosphorylation of Akt, MAPK and expression of NF-κB were decreased in both BT-474 and SK-BR-3-hr cells. In the BT-474 xenograft model, though not as much as herceptin, curcumin did effectively decrease the tumor size. The combination of curcumin with herceptin was not better than herceptin alone; however, the combination of taxol and curcumin had an antitumor effect comparable with taxol and herceptin. The results suggested that curcumin has potential as a treatment for HER-2-overexpressed breast cancer

Multiplex PCR System for Rapid Detection of Pathogens in Patients with Presumed Sepsis – A Systemic Review and Meta-Analysis

Background: Blood culture is viewed as the golden standard for the diagnosis of sepsis but suffers from low sensitivity and long turnaround time. LightCycler SeptiFast (LC-SF) is a real-time multiplex polymerase chain reaction test able to detect 25 common pathogens responsible for bloodstream infections within hours. We aim to assess the accuracy of LC-SF by systematically reviewing the published studies. Method Related literature on Medline, Embase, and Cochrane databases was searched up to October 2012 for studies utilizing LC-SF to diagnose suspected sepsis and that provided sufficient data to construct two-by-two tables. Results: A total of 34 studies enrolling 6012 patients of suspected sepsis were included. The overall sensitivity and specificity for LC-SF to detect bacteremia or fungemia was 0·75 (95% CI: 0·65–0·83) and 0·92 (95%CI:0·90–0·95), respectively. LC-SF had a high positive likelihood ratio (10·10) and a moderate negative likelihood ratio (0·27). Specifically, LC-SF had a sensitivity of 0·80 (95%CI: 0·70–0·88) and a specificity of 0·95(95%CI: 0·93–0·97) for the bacteremia outcome, and a sensitivity of 0·61 (95%CI: 0·48–0·72) and a specificity of 0·99 (95%CI: 0·99–0·99) for the fungemia outcome. High heterogeneity was found in the bacteremia outcome subgroup but not in the fungemia outcome subgroup. Conclusion: LC-SF is of high rule-in value for early detection of septic patients. In a population with low pretest probability, LC-SF test can still provide valuable information for ruling out bacteremia or fungemia

Bmi-1 Regulates Snail Expression and Promotes Metastasis Ability in Head and Neck Squamous Cancer-Derived ALDH1 Positive Cells

Recent studies suggest that ALDH1 is a putative marker for HNSCC-derived cancer stem cells. However, the regulation mechanisms that maintain the stemness and metastatic capability of HNSCC-ALDH1+ cells remain unclear. Initially, HNSCC-ALDH1+ cells from HNSCC patient showed cancer stemness properties, and high expression of Bmi1 and Snail. Functionally, tumorigenic properties of HNSCC-ALDH1+ cells could be downregulated by knockdown of Bmi-1. Overexpression of Bmi-1 altered in expression property ALDH1− cells to that of ALDH1+ cells. Furthermore, knockdown of Bmi-1 enhanced the radiosensitivity of radiation-treated HNSCC-ALDH1+ cells. Moreover, overexpression of Bmi-1 in HNSCC-ALDH1− cells increased tumor volume and number of pulmonary metastatic lesions by xenotransplant assay. Importantly, knock-down of Bmi1 in HNSCC-ALDH1+ cells significantly decreased distant metastases in the lungs. Clinically, coexpression of Bmi-1/Snail/ALDH1 predicted the worst prognosis in HNSCC patients. Collectively, our data suggested that Bmi-1 plays a key role in regulating Snail expression and cancer stemness properties of HNSCC-ALDH1+ cells

A Combined DNA-Affinic Molecule and N-Mustard Alkylating Agent Has an Anti-Cancer Effect and Induces Autophagy in Oral Cancer Cells

Although surgery or the combination of chemotherapy and radiation are reported to improve the quality of life and reduce symptoms in patients with oral cancer, the prognosis of oral cancer remains generally poor. DNA alkylating agents, such as N-mustard, play an important role in cancer drug development. BO-1051 is a new 9-anilinoacridine N-mustard-derivative anti-cancer drug that can effectively target a variety of cancer cell lines and inhibit tumorigenesis in vivo. However, the underlying mechanism of BO-1051-mediated tumor suppression remains undetermined. In the present study, BO-1051 suppressed cell viability with a low IC50 in oral cancer cells, but not in normal gingival fibroblasts. Cell cycle analysis revealed that the tumor suppression by BO-1051 was accompanied by cell cycle arrest and downregulation of stemness genes. The enhanced conversion of LC3-I to LC3-II and the formation of acidic vesicular organelles indicated that BO-1501 induced autophagy. The expression of checkpoint kinases was upregulated as demonstrated with Western blot analysis, showing that BO-1051 could induce DNA damage and participate in DNA repair mechanisms. Furthermore, BO-1051 treatment alone exhibited a moderate tumor suppressive effect against xenograft tumor growth in immunocompromised mice. Importantly, the combination of BO-1051 and radiation led to a potent inhibition on xenograft tumorigenesis. Collectively, our findings demonstrated that BO-1051 exhibited a cytotoxic effect via cell cycle arrest and the induction of autophagy. Thus, the combination of BO-1051 and radiotherapy may be a feasible therapeutic strategy against oral cancer in the future

Effects of Gas Composition on Highly Efficient Surface Modification of Multi-Walled Carbon Nanotubes by Cation Treatment

Abstract High incident energy hydrogen and/or oxygen cations are generated by electron cyclotron resonance system, and then used to highly efficiently modify multi-walled carbon nanotubes (MWCNTs). The effects of various H2/O2 gas compositions on the modification process are studied. A systematic characterization method utilizing a combination of X-ray photoelectron spectroscopy (XPS), scanning electron microscopy, Raman spectroscopy, and thermogravimetric analysis (TGA) is used to evaluate the effects of various H2/O2gas compositions on MWCNT functionalization. The Raman results show that the I D/IG ratio is directly affected by H2 concentration in gas mixture, and the treatment applying a H2/O2 gas mixture with ratio of 40/10 (sccm/sccm) can yield the nanotubes with the highest I D/I G ratio (1.27). The XPS results suggest that the gas mixture with ratio of 25/25 (sccm/sccm) is most effective in introducing oxygen-containing functional groups and reducing amorphous carbon. The TGA suggests that the structural change of the treated nanotubes is marginal by this method with any gas condition.</p

Differences in accuracy and underestimation rates for 14- versus 16-gauge core needle biopsies in ultrasound-detectable breast lesions

Core needle biopsy (CNB) was widely used in the diagnosis of ultrasound-detectable breast lesions. We aimed at assessing the diagnostic performance differences between 14- and 16-gauge ultrasound-guided core biopsies. This retrospective study enrolled patients receiving CNB from January 2001 to December 2007. The results of 14- and 16-gauge breast CNBs were compared with pathology reports of open surgical biopsy (OSB). A total of 1024 paired CNB and OSB results were obtained from 1732 CNB procedures in 1630 patients.Those CNB results reached 92.9% sensitivity, 99.7% specificity, 5.96% underestimation, and 94.8% accuracy rates. There was no difference in sensitivity (p = 0.17) or specificity (p = 0.38) between 14- and 16-gauge needles. However, better overall accuracy (p = 0.02), less underestimation (p < 0.001), and lower false-negative (p = 0.02) rates were found for the 14-gauge CNB. Regarding accuracy and underestimation rates, a 14-gauge needle is preferred to a 16-gauge one in ultrasound-guided biopsies

Differences in accuracy and underestimation rates for 14- versus 16-gauge core needle biopsies in ultrasound-detectable breast lesions

Background/Objective: Core needle biopsy (CNB) was widely used in the diagnosis of ultrasound-detectable breast lesions. We aimed at assessing the diagnostic performance differences between 14- and 16-gauge ultrasound-guided core biopsies. Methods: This retrospective study enrolled patients receiving CNB from January 2001 to December 2007. The results of 14- and 16-gauge breast CNBs were compared with pathology reports of open surgical biopsy (OSB). Results: A total of 1024 paired CNB and OSB results were obtained from 1732 CNB procedures in 1630 patients.Those CNB results reached 92.9% sensitivity, 99.7% specificity, 5.96% underestimation, and 94.8% accuracy rates. There was no difference in sensitivity (p = 0.17) or specificity (p = 0.38) between 14- and 16-gauge needles. However, better overall accuracy (p = 0.02), less underestimation (p < 0.001), and lower false-negative (p = 0.02) rates were found for the 14-gauge CNB. Conclusion: Regarding accuracy and underestimation rates, a 14-gauge needle is preferred to a 16-gauge one in ultrasound-guided biopsies