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Performing maintenance checks and state detection of machines with rotary actuators in industry is a challenging task which requires expensive and complicated equipment. One of the ways to perform this is using a system based on recording and analysis of sounds the machine makes during operation. This paper describes an approach which uses a simple, compact device based on a commercial microcomputer that aims to entirely replace the state detection system. It is able to record acoustic signals in close proximity to the machine, process them and use a neural network to output the state of the rotary actuator. The testing has been done on real acoustic signals recorded in the thermal power plant Kostolac in Serbia.

Rotary actuators are among the most commonly used machines in the industry and the algorithm for detecting the level of wear they are subjected to can prevent significant amount of unnecessary maintenance expenses. This paper proposes a new algorithm which can detect the state of the rotating machine using acoustic signals recorded in its vicinity. The algorithm uses a combination of wavelet transform and neural networks and is computationally inexpensive, so it can be implemented on a simple microcontroller. The testing has been done on real acoustic signals recorded in thermal power plant Kostolac in Serbia.

High demands for increasing robustness, safety, and efficiency in thermal power plants are the main motivation behind ongoing attempts to optimize combustion. This paper presents a study of modeling and control of the combustion process in a tangentially fired pulverized-coal boiler. It proposes an approach to flame geometry and position control by means of reallocation of firing. Such control ensures flame focus maintenance away from the walls of the boiler, and thus prevents many unwanted by-products of combustion. In addition, uniform heat dissipation over mills enhances the energy efficiency and reliability of the boiler. First, experimental data obtained from the 350-MW boiler of the Nikola Tesla power plant, Serbia, are analyzed in detail. This results in a model identification procedure using an adaptive parameter estimation method. Second, constrained multivariate extremum seeking (ES) is proposed in this paper, to optimally tune boiler operation in order to maintain the desired flame configuration in the furnace. Finally, the effectiveness of the ES adaptive controller in the presence of disturbances is demonstrated through simulations performed on the experimentally identified model of the boiler.

Major limitations of camptothecin anticancer drugs (toxicity, nonselectivity, water insolubility, inactivation by human serum albumin) may be improved by creating glucuronide prodrugs that rely on beta-glucuronidase for their activation. We found that the camptothecin derivative 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC) displays greater cytotoxicity against cancer cells than the clinically used camptothecin derivatives SN-38 and topotecan even in the presence of human serum albumin. We synthesized the prodrug BQC-glucuronide (BQC-G), which was 4000 times more water soluble and 20-40 times less cytotoxic than BQC. Importantly, even in the presence of human serum albumin, BQC-G was efficiently hydrolyzed by beta-glucuronidase and produced greater cytotoxicity (IC50 = 13 nM) than camptothecin, 9-aminocamptothecin, SN-38, or topotecan (IC503000, 1370, 48, and 28 nM, respectively). BQC-G treatment of mice bearing human colon cancer xenografts with naturally or artificially elevated beta-glucuronidase activity produced significant antitumor activity, showing that BQC-G is a potent prodrug suitable for selective intratumoral drug activation.

In this paper, we propose a vessel detection algorithm used in an online laser monitoring system in the lock of a hydropower plant. The system has to ensure the strict detection of the position of a vessel in order to prevent the manipulation of pound lock doors while the vessel is in the door zone. This paper describes in detail the monitoring concept, i.e., the detection algorithm implemented in the computer program that performs object detection in the view field of laser scanners. The detection algorithm has been developed in accordance with the modular principle and contains a number of functional partitions based on pattern recognition, i.e., the partition for the recognition of interference, the partition for water surface recognition in the conditions of debris floating on the water surface, the partition for the recognition of interference caused by the overflight of a single bird or a flock of birds, the partition for the recognition of interference caused by meteorological conditions, the partition for the recognition of high waves, and the partition for the recognition and detection of vessels. The main parts of the monitoring system are as follows: infrared laser scanners, controllers, an industrial PC, developed software with the implemented detection algorithm, a database, and a SCADA interface. This monitoring system has a vital role in keeping water transport operations safe and in the preventive maintenance and avoidance of vessel damaging in the area of gates at each end that controls the level of water in the lock chambers. The implementation of the detection algorithm has significantly improved the characteristics of the monitoring system. The system successfully detects all vessels, whereas the number of false detections remains neglectable.

The paper proposes a method for state change detection in rotary machines. The procedure relies on recorded signals spectrogram analysis and features appropriate for texture classification in digital images. Final classification in terms of machine health is performed using Adaboost algorithm. The application of this algorithm is proposed for thermal power plant fan mills whose impact plates are damaged during the coal grinding process. The main goal of the procedure is to detect the amount of wear of the impellers and to determine the appropriate timing for unnecessary maintenance tasks. Real acoustic signals for verification of this algorithm are recorded in thermal power plant Kostolac A1 in a coal grinding subsystem.

Monitoring levels of Irinotecan and its metabolites during cancer therapy could help link broad interpatient variations in antitumor activity and toxicity to the patient's metabolic status. We have developed and validated a versatile and highly sensitive method for the simultaneous determination of Irinotecan and its clinically relevant metabolites 7-ethyl-10-hydroxy-camptothecin (SN-38) and SN-38 glucuronide. Sample clean-up involves precipitation by acetone/methanol/0.5 M trichloroacetic acid at 4:4:2 v/v followed by extraction of the metabolites on an SPE column by 20% methanol in 25 mM KH2 PO4 pH 2.9. Online transfer to an analytical μBondapak C18 column, elution with 24% acetonitrile (ACN) in 0.1 M KH2 PO4 pH 2.9 and fluorescence detection with excitation at 375 nm and emission at 430 nm for SN-38 glucuronide and Irinotecan or 540 nm for SN-38 results in high sensitivity (1-2 pg) and short (∼10 min) run times. The method was used to determine the degree of SN-38 glucuronidation in mice after Irinotecan administration and in cultured cancer cells exposed to SN-38. The method may be used to better understand Irinotecan metabolism, personalize therapy, and develop Irinotecan-based tumor targeting therapies.

Design of an expert system based on Hidden Markov Models for recognition of radar targets in a zone of ground surveillance radar is presented in the paper. Parameters of the real radar echo signal represented in a form of autoregressive models are used as an input of the designed expert system. The real radar echoes have been collected for the purpose of this research. Obtained results show that designed system has some certain advantages, but there are also some limitations in recognition of the analyzed sequences.

CPT-11 is a clinically important prodrug that requires conversion into the active metabolite SN-38, a potent topoisomerase I poison, for antitumor activity. However, SN-38 is rapidly metabolized to the inactive SN-38 glucuronide (SN-38G) in the liver, which reduces the amount of SN-38 available for killing cancer cells. Here, we investigated if local expression of β-glucuronidase (βG) on cancer cells to catalytically convert SN38G to SN38 could enhance the antitumor activity of CPT-11. βG was tethered on the plasma membrane of three different human cancer cell lines: human colon carcinoma (LS174T), lung adenocarcinoma (CL1-5) and bladder carcinoma (EJ). Surface β-glucuronidase-expressing cells were 20 to 80-fold more sensitive to SN-38G than the parental cells. Intravenous CPT-11 produced significantly greater suppression of CL1-5 and LS174 T tumors that expressed βG as compared with unmodified tumors. Furthermore, an adenoviral vector expressing membrane-tethered βG (Ad.βG) increased the sensitivity of cancer cells to SN-38G even at multiplicity of infections as low as 0.16, indicating bystander killing of non-transduced cancer cells. Importantly, intratumoral injection of Ad.βG significantly enhanced the in vivo antitumor activity of CPT-11 as compared with treatment with CPT-11 or Ad vectors alone. This study shows that Ad.βG has potential to boost the therapeutic index of CPT-11.

The aim of this study was to investigate the clinical effects of low-level laser therapy (LLLT) in patients with acute low back pain (LBP) with radiculopathy.Acute LBP with radiculopathy is associated with pain and disability and the important pathogenic role of inflammation. LLLT has shown significant anti-inflammatory effects in many studies.A randomized, double-blind, placebo-controlled trial was performed on 546 patients. Group A (182 patients) was treated with nimesulide 200 mg/day and additionally with active LLLT; group B (182 patients) was treated only with nimesulide; and group C (182 patients) was treated with nimesulide and placebo LLLT. LLLT was applied behind the involved spine segment using a stationary skin-contact method. Patients were treated 5 times weekly, for a total of 15 treatments, with the following parameters: wavelength 904 nm; frequency 5000 Hz; 100-mW average diode power; power density of 20 mW/cm(2) and dose of 3 J/cm(2); treatment time 150 sec at whole doses of 12 J/cm(2). The outcomes were pain intensity measured with a visual analog scale (VAS); lumbar movement, with a modified Schober test; pain disability, with Oswestry disability score; and quality of life, with a 12-item short-form health survey questionnaire (SF-12). Subjects were evaluated before and after treatment. Statistical analyses were done with SPSS 11.5.Statistically significant differences were found in all outcomes measured (p0.001), but were larger in group A than in B (p0.0005) and C (p0.0005). The results in group C were better than in group B (p0.0005).The results of this study show better improvement in acute LBP treated with LLLT used as additional therapy.

Irinotecan (CPT-11) is a clinically important anticancer prodrug that requires enzymatic hydrolysis by carboxyesterase to generate the active metabolite SN-38. However, SN-38 is further metabolized to inactive SN-38 glucuronide (SN-38G), thus diminishing the levels of active SN-38. Although exogenously administered glucuronide drugs are being investigated for cancer therapy, it is unknown if endogenously generated camptothecin glucuronide metabolites can be used for tumor therapy. Here, we tested the hypothesis that tumor-located hydrolysis of endogenously generated SN-38G can enhance the antitumor efficacy of CPT-11 therapy. EJ human bladder carcinoma cells expressing membrane-tethered β-glucuronidase (EJ/mβG cells) were used to selectively hydrolyze SN-38G to SN-38. Parental EJ and EJ/mβG cells displayed similar in vitro and in vivo growth rates and sensitivities to CPT-11 and SN-38. By contrast, EJ/mβG cells were more than 30 times more sensitive than EJ cells to SN-38G, showing that SN-38 could be generated from SN-38G in vitro. Systemic administration of CPT-11 resulted in tumor-located hydrolysis of SN-38G and accumulation of SN-38 in EJ/mβG subcutaneous tumors. Importantly, systemic administration of CPT-11, which itself is not a substrate for β-glucuronidase, dramatically delayed the growth of EJ/mβG xenografts without increased systemic toxicity. Thus, the anticancer activity of CPT-11 can be significantly enhanced by converting the relatively high levels of endogenously generated SN-38G to SN-38 in tumors. The high concentrations of SN-38G found in the serum of patients treated with CPT-11 suggest that clinical response to CPT-11 may be improved by elevating β-glucuronidase activity in tumors. [Mol Cancer Ther 2009;8(4):940–6]

Human beta-glucuronidase, due to low intrinsic immunogenicity in humans, is an attractive enzyme for tumor-specific prodrug activation, but its utility is hindered by low activity at physiological pH. Here we describe the development of a high-throughput screening procedure for enzymatic activity based on the stable retention of fluorescent reaction product in mammalian cells expressing properly folded glycoproteins on their surface. We utilized this procedure on error-prone PCR and saturation mutagenesis libraries to isolate beta-glucuronidase tetramers that were up to 60-fold more active (k(cat)/K(m)) at pH 7.0 and were up to an order of magnitude more effective at catalyzing the conversion of two structurally disparate glucuronide prodrugs to anticancer agents. The screening procedure described here can facilitate investigation of eukaryotic enzymes requiring posttranslational modifications for biological activity.

We consider the problem of detecting malfunctions in the actuators or sensors of systems which can be described by nonlinear/non-Gaussian stochastic state-space models. The basic idea is to estimate the state vector of such models using a sequential Monte Carlo technique known as particle filtering. We present several approaches to detecting faults and pinpointing their location within the system, using either one or a bank of particle filters.

Mast cells (MCs) have been identified in various tumors; however, the role of these cells in tumorigenesis remains controversial. Here, we quantified MCs in human and murine malignant pleural effusions (MPEs) and evaluated the fate and function of these cells in MPE development. Evaluation of murine MPE-competent lung and colon adenocarcinomas revealed that these tumors actively attract and subsequently degranulate MCs in the pleural space by elaborating CCL2 and osteopontin. MCs were required for effusion development, as MPEs did not form in mice lacking MCs, and pleural infusion of MCs with MPE-incompetent cells promoted MPE formation. Once homed to the pleural space, MCs released tryptase AB1 and IL-1 beta, which in turn induced pleural vasculature leakiness and triggered NF-kappa B activation in pleural tumor cells, thereby fostering pleural fluid accumulation and tumor growth. Evaluation of human effusions revealed that MCs are elevated in MPEs compared with benign effusions. Moreover, MC abundance correlated with MPE formation in a human cancer cell-induced effusion model. Treatment of mice with the c-KIT inhibitor imatinib mesylate limited effusion precipitation by mouse and human adenbcarcinoma cells. Together, the results of this study indicate that MCs are required for MPE formation and suggest that MC-dependent effusion formation is therapeutically addressable.

Gene-mediated enzyme prodrug therapy (GDEPT) seeks to increase the therapeutic index of anti-neoplastic agents by promoting selective activation of relatively nontoxic drug derivatives at sites of specific enzyme expression. Glucuronide prodrugs are attractive for GDEPT due to their low toxicity, bystander effect in the interstitial tumor space and the large range of possible glucuronide drug targets. In this study, we expressed human, murine and Esherichia coli beta-glucuronidase on tumor cells and examined their in vitro and in vivo efficacy for the activation of glucuronide prodrugs of 9-aminocamptothecin and p-hydroxy aniline mustard. We show that (1) fusion of beta-glucuronidase to the Ig-like C(2)-type and Ig-hinge-like domains of the B7-1 antigen followed by the B7-1 transmembrane domain anchored high levels of active murine and human beta-glucuronidase on cells, (2) strong bystander killing of tumor cells was achieved in vitro by murine beta-glucuronidase activation of prodrug, (3) potent in vivo anti-tumor activity was achieved by prodrug treatment of tumors that expressed murine beta-glucuronidase and (4) the p-hydroxy aniline prodrug was more effective in vivo than the 9-aminocamptothecin prodrug. Our results demonstrate that surface expression of murine beta-glucuronidase for activation of a glucuronide prodrug of p-hydroxy aniline mustard may be useful for more selective therapy of cancer.

The exceptionally high protein concentration in living cells can favor functional protein-protein interactions that can be difficult to detect with purified proteins. In this study we describe specific interactions between mammalian D-glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and L-lactate dehydrogenase (LDH) isozymes from heart and muscle. We use poly(ethylene-glycol) (PEG)-induced coprecipitation and native agarose electrophoresis as two independent methods uniquely suited to mimic some of the conditions that can favor protein-protein interaction in living cells. We found that GAPDH interacts with heart or muscle isozymes of LDH with approximately one-to-one stoichiometry. The interaction is specific; GAPDH shows interaction with two LDH isozymes that have very different net charge and solubility in PEG solution, while no interaction is observed with GAPDH from other species, other NAD(H) dehydrogenases, or other proteins that have very similar net charge and molecular mass. Analytical ultracentrifugation showed that the LDH and GAPDH complex is insoluble in PEG solution. The interaction is abolished by saturation with NADH, but not by saturation with NAD(+) in correlation with GAPDH solubility in PEG solution. The crystal structures show that GAPDH and LDH isozymes share complementary size, shape, and electric potential surrounding the active sites. The presented results suggest that GAPDH and LDH have a functional interaction that can affect NAD(+)/NADH metabolism and glycolysis in living cells.

We followed the cytosine C(5) exchange reaction with Dnmt1 to characterize its preference for different DNA substrates, its allosteric regulation, and to provide a basis for comparison with the bacterial enzymes. We determined that the methyl transfer is rate-limiting, and steps up to and including the cysteine-cytosine covalent intermediate are in rapid equilibrium. Changes in these rapid equilibrium steps account for many of the previously described features of Dnmt1 catalysis and specificity including faster reactions with premethylated DNA versus unmethylated DNA, faster reactions with DNA in which guanine is replaced with inosine [poly(dC-dG) vs poly(dI-dC)], and 10-100-fold slower catalytic rates with Dnmt1 relative to the bacterial enzyme M.HhaI. Dnmt1 interactions with the guanine within the CpG recognition site can prevent the premature release of the target base and solvent access to the active site that could lead to mutagenic deamination. Our results suggest that the beta-elimination step following methyl transfer is not mediated by free solvent. Dnmt1 shows a kinetic lag in product formation and allosteric inhibition with unmethylated DNA that is not observed with premethylated DNA. Thus, we suggest the enzyme undergoes a slow relief from allosteric inhibition upon initiation of catalysis on unmethylated DNA. Notably, this relief from allosteric inhibition is not caused by self-activation through the initial methylation reaction, as the same effect is observed during the cytosine C(5) exchange reaction in the absence of AdoMet. We describe limitations in the Michaelis-Menten kinetic analysis of Dnmt1 and suggest alternative approaches.

9-aminocamptothecin glucuronide (9ACG) is a new water-soluble prodrug of 9-aminocamptothecin (9AC) that is a substrate for beta-glucuronidase and displays potent antitumor activity against human tumor xenografts. The lactone ring of camptothecins (CPTs) is required for antitumor activity but spontaneously opens under physiological conditions to an inactive carboxy form. The carboxy form of many CPTs, including 9AC, preferentially binds to human serum albumin (HSA), which further reduces the equilibrium amount of active lactone and greatly decreases antitumor efficacy. In this study, we examined the hypothesis that the unique structure of 9ACG might alter prodrug interaction with HSA and increase 9ACG lactone stability as compared with 9AC. HPLC analysis revealed that HSA did not affect the equilibrium level of 9ACG lactone whereas both CPT lactone and 9AC lactone were greatly reduced in the presence of HSA as compared to their equilibrium levels in PBS. Similar results were found in human serum and whole blood. The lactone ring of 9ACG also opened more slowly (t(1/2)=50 min) as compared with 9AC (t(1/2)=20 min) in the presence of HSA. Both 9ACG lactone and 9ACG carboxy bound HSA with similar affinities (K(D) approximately 4.5 x 10(-5)M(-1)). Binding of 9ACG to HSA reduced prodrug toxicity to cancer cells by about 10-fold in vitro. Injection of HSA into nude mice prolonged the half-life of 9ACG by about 3-fold, indicating that albumin-bound 9ACG lactone may act as a depot of active prodrug in vivo. Our results suggests that in contrast to CPT and 9AC, HSA does not appear to adversely affect 9ACG and may enhance the selective antitumor activity of 9ACG in tumors that contain beta-glucuronidase.

Capital project development is a complex process that takes many years to implement. The development of a capital project usually undergoes several rounds of design evolution, and as a result the basic and original customer’s requirements may be easily sidetracked or may deviate from the client’s objectives. Quality function deployment (QFD) is a tool that can be used to keep track of customers’ requirements. The objective of this paper is to explore the applicability of QFD in the civil engineering capital project planning process by developing a QFD model with an application template for the process. To verify and demonstrate how the QFD model works, data are obtained from two real-life projects and fed into the template for back-analysis. The findings suggest that QFD can be successfully used in the capital project planning process as a road map to keep track of the original requirements, facilitate good communication across the hierarchy, and serve as a tool for evaluating project alternatives.

Remote supervision of railway axle counter's operation provides real-time information about activities in railway network and early signs of system failure. Remote supervision of safety critical systems, like this, has to be robust and unambiguous. In this paper is given one possible realization of such system.

To successfully compete in the long term, a company must be sure current customers are satisfied. Providing superior quality and keeping customers satisfied are rapidly becoming the ways companies differentiate themselves from competitors. This study examines empirically home builders' performance as measured by the degree of home buyers' satisfaction. Sixteen Florida-based home builders agreed to participate in the study and to allow contact with their recent home buyers. Nearly 300 of these home buyers provided valuable input to the study. A model was proposed, describing home-buyer satisfaction as a three-dimensional composite of satisfaction with house design, house quality, and service. All three dimensions were found to be significant predictors of overall home-buyer satisfaction. Service emerged as the most important component in shaping the overall satisfaction. However, service was the area in which home builders demonstrated the poorest performance. The study results suggest that service deserve...

The equivalence between the Kalman filter and a particular least squares regression problem is established and the regression problem is solved robustly using a statistical approach, named M-estimation. M-robust estimators are derived for adaptive estimation of the unknown a priori state and observation noise statistics simultaneously with the system states. The feasibility of the approach is demonstrated with simulation.