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OBJECTIVE: To investigate the role of human serum albumin (hsa)_circular (circ)_0000711 in hepatocellular carcinoma (HCC). Circular ribonucleic acids (circRNAs) are proven in numerous studies to play crucial role in tumor biology, but their roles in HCC remain unknown to a great extent. PATIENTS AND METHODS: The circRNA expression profile microarray was employed to screen differentially expressed circRNAs in tumor tissues and adjacent tissues from HCC patients, and Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) assay was performed for further verification. Next, the target micro RNAs (miRNAs) and their messenger RNAs (mRNAs) of key circRNAs were predicted by bioinformatics software, and a circRNA-miRNA- mRNA regulatory network was constructed. Subsequently, KEGG and GO enrichment analyses were applied to predict the possible biological processes regulated by hsa_circ_0000711 and relevant signaling pathways. The miRNAs playing a key role in the circRNA-miRNA-mRNA regulatory network were then selected as the objects, and their direct binding to hsa_ circ_0000711 was confirmed via luciferase reporter gene assay. Thereafter, hsa_circ_0000711 was overexpressed or knocked out, and the biological function of hsa_circ_0000711 was detected by cell counting kit-8 (CCK-8) assay, apoptosis detection, and 5-Ethynyl-2'-deoxyuridine (EdU) staining assay in vitro. RESULTS: The results of expression profile screening revealed that there was a significant difference in the expression profile of circRNAs between tumor tissues and adjacent tissues in HCC patients. Based on the circRNA expression profile and RT-qPCR results, the expression level of hsa_circ_0000711 was overtly reduced in HCC tissues. In addition, miR-103a- 3p had the highest eigenvector centrality in the circRNA-miRNA-mRNA regulatory network, suggesting that miR-103a-3p is a vital participant in the pathological mechanism of hsa_ circ_0000711. The KEGG enrichment analysis results pointed out that the target genes regulated by hsa_circ_0000711 were clearly enriched in the tumor-associated signaling pathways. Besides, the results of GO enrichment analysis demonstrated that the biological processes regulated by hsa_circ_0000711 were mainly related to cell cycle regulation, so cell proliferation might be affected. The results of luciferase reporter gene and RT-qPCR assays showed that hsa_circ_0000711 directly bound to has-miR-103a-3p to serve as a molecular sponge. The results of CCK-8 and EdU staining assays revealed that the proliferation of hepatoma cells in hsa_circ_0000711 overexpression group was evidently enhanced. In addition, it was further found via flow cytometry that the apoptosis rate of cells was significantly raised in hsa_circ_0000711 low-expression group and dramatically declined in hsa_circ_0000711 overexpression group. CONCLUSIONS: Overexpression of hsa_ circ_0000711 promoted the proliferation and inhibited the apoptosis of hepatoma cells via targeting has-miR-103a-3p. [ABSTRACT FROM AUTHOR]

In this paper, a new rotary-linear switched-reluctance motor with a magnetic decoupled structure is introduced. The rotational motion of the motor, managed by a sliding-mode controller, is coordinated with the proportional-derivation linear motion by using a fuzzy logic block. Consequently, both rotational and linear motions can be realized simultaneously. In addition, the decoupled magnetic paths of the motor in two directions are analyzed by finite-element method, with the force and torque measurements suggesting the feasibility of the motor. Both the simulation and experimental results show that the motor is totally decoupled in the linear and rotary directions. The linear movement and the rotation at the same time validate the effectiveness of the motor design and the proposed control method, with highly accurate responses for the two degrees of freedom movement. [ABSTRACT FROM AUTHOR]

This paper discusses the tracking coordination of a linear switched reluctance machine (LSRM) network based on a global feedback control strategy with a full-state observation framework. The observer is allocated on the follower instead of the leader to form a leader--follower--observer network, by utilizing the leader as the global feedback tracking controller and the observer as the observation of the full states. The internal model compensator (IMC) is applied to the leader for the improvement of the network performance. The full-state information of the LSRM network is reconfigured by the output of the LSRM where the observer is located to provide necessary feedback information to the leader. Then, the controllability and observability of the leader--follower--observer network with the IMC are inspected, serving as a basis for the design of the global controller with the IMC and full-state observer. Experimentation verifies the effectiveness of the proposed network control scheme and the results demonstrate that both the absolute and the relative accuracy can be simultaneously improved, compared to the LSRM network with only the consensus algorithm and no global feedback mechanism. [ABSTRACT FROM AUTHOR]

This paper proposes a coordinated positioning control network for three direct drive, linear switched reluctance machines. To obtain the optimized network control parameters, the distributed linear quadratic regulator is applied. Different communication topologies are studied for both the dynamic tracking and the coordination performance of the network. Experimental results demonstrate that an absolute static tracking precision of 20~\mu \textm can be achieved from the “cycle” communication topology and an absolute static coordination precision of 11~\mu \textm can be obtained from the “path” communication topology. [ABSTRACT FROM AUTHOR]

In this paper, a novel direct drive, bilateral planar switched reluctance generator (BPSRG) is developed for 2-D wave energy conversion with a mixed type of flux circulation. The proposed BPSRG has longitudinal flux type of the magnetic circuit on one direction and transverse flux-type magnetic circulation for the other perpendicular direction. The characteristics of the magnetic flux and static inductance are calculated for the BPSRG based on the 3-D finite-element method, in order to ensure negligible coupling effect between any phases. Theoretical model of the BPSRG is derived, and parameters that impact the open-loop operation performance of the power generation are analyzed, optimized, and supported by experimental results. [ABSTRACT FROM AUTHOR]

In this paper, an approach combining current pulses injection and fuzzy logic observer to measure the air gap length of linear machines is proposed. A polymer enclosed by a coil is produced and selected as the test object. The characteristics and production process for the polymer is introduced and its magnetic feature has been studied. Injecting current pulses is used to calculate the self-inductance of the coil fixed on the cores that is directly influenced by the air gap length from the polymer. By using a fuzzy logic observer, the air gap length can be estimated precisely according to the variations of the self-inductance. Experimental results show the effectiveness of the proposed measurement method and the results prove that the proposed method is suitable for the air gap measurement for linear machines. [ABSTRACT FROM AUTHOR]

A fuzzy position controller is employed for the linear switched reluctance motor. Performance comparison between the fuzzy controller and a proportional-differential (PD) controller is carried out. Under the PD controller, the absolute steady-state error is 44.5 ~211.5 μm under normal condition and 1157–1212 μm under sustained time-variant disturbance circumstance, respectively. The absolute steady-state error of 3 μm and 9 μm can be achieved under the fuzzy controller in the normal and sustained disturbed circumstance. Experimental results demonstrate that the position tracking performance from the proposed algorithm is superior to the conventional PD control strategy, both in normal circumstance and disturbance environment. [ABSTRACT FROM AUTHOR]

This paper investigates a distributed, coordinated motion control network based on multiple direct-drive, linear switched reluctance machines (LSRMs). A hierarchical, two-level synchronization control strategy is proposed for the four LSRMs based motion control network. The high-level, reference signals agreement algorithm is first employed to correct the asynchronous behaviors of the position commands. Then, the low-level tracking synchronization method is applied for the collaborative position control of the four LSRMs. The proposed two-level, fault-tolerant control strategy eliminates the asynchrony of the reference signals and it also guarantees the coordinated tracking control performance of the four LSRMs. Experimental results demonstrate that effective coordinated tracking control can be ensured, based on the successful agreement of reference signals and an absolute tracking error falling within 2 mm can be achieved. [ABSTRACT FROM AUTHOR]

The coordinated tracking control for the group motion control system based on three direct-drive double-sided linear switched reluctance motors (LSRMs) is investigated in this paper. The system construction for the proposed coordinated tracking system is elaborated, including the unit system and group system design, communication configuration among unit systems, and stability and performance analysis of the group system. The coordinated control performance is concentrated on three identical LSRMs with different communication topologies. Experimental results demonstrate that necessary bidirectional interactions between the unit systems contribute to the coordination performance. The maximum dynamic tracking error within ±0.4 mm can be achieved under the sinusoidal reference of 30-mm amplitude and 0.2-Hz frequency. [ABSTRACT FROM PUBLISHER]

In this paper, to enhance the machine performance and realize a high-precision position control performance, a dual-loop position controller is employed for the asymmetric bilateral linear hybrid switched reluctance motor (ABLHSRM). Machine characteristics are investigated by finite-element method. The dual-loop controller is constructed by employing a tradition proportional–integral differential velocity controller as the inner loop and a fuzzy proportional differential (PD) controller for the outer loop. Experimental results demonstrate that both the position control performance and the velocity control performance under the dual-loop control algorithm are superior to the single-loop PD position control strategy. An absolute steady-state error of 4 \mu \textm can be achieved under the dual-loop control strategy. Performance comparison from the ABLHSRM and its asymmetric bilateral linear switched reluctance counterpart with the same dimensions are carried out. Position tracking results show that the rise time is improved for the proposed ABLHSRM under the proposed control scheme. [ABSTRACT FROM AUTHOR]

An adaptive high-precision position control algorithm with online system identification is implemented onto the switched reluctance, two-finger gripper with coupled magnetic paths. Theoretical investigation proves that the magnetic paths from the two fingers are highly coupled. Without the introduction of any decoupling scheme, the position control performance under the proportional integral differential controller and the adaptive controller is inspected and the control results are compared. Experimental results verify that, without introducing any decoupling mechanism, the adaptive controller is capable of independent control of each finger with a high-precision and uniform position control performance. [ABSTRACT FROM AUTHOR]

In the advanced manufacturing industry, planar switched reluctance motors (PSRMs) have proved to be a promising candidate due to their advantages of high precision, low cost, low heat loss, and ease of manufacture. However, their inverse force function, which provides vital phase current command for precise motion, is highly nonlinear and hard to be accurately modeled. This paper proposes a novel inverse force function using sparse least squares support vector machines (LS-SVMs) to achieve nonlinear modeling for precise motion of a PSRM. The required training and testing sets of sparse LS-SVMs are first obtained from experimental measurement. A sparse LS-SVMs regression is further developed using training set to accurately model the inverse force function. Accordingly, the function is tested via the testing set to assess its feasibility. Finally, the proposed approach is applied to the PSRM system with dSPACE controller for trajectory tracking, and its effectiveness and superior performance are verified through experimental results. [ABSTRACT FROM PUBLISHER]

A direct-drive generator based on linear switched reluctance principle is investigated for wave energy utilization. Integrated with the sensorless technique, the direct-drive generator has the characteristics of low cost and robustness, and the power generation control system is especially suitable for the operation under hostile working environments since restrictions of physical sensors are eliminated. Simulation analysis based on the finite element methods (FEM) and joint simulation are carried out for performance analysis of the power generation control system, including position estimation, open loop turn-on and turn-off position optimization and closed loop current regulation. Experimental results validate the effectiveness of the position estimation scheme for the sensorless, linear switched reluctance generator based power generation control system. [ABSTRACT FROM AUTHOR]

In planar switched reluctance motors (PSRMs), the electromagnetic force ripple minimization is important to reduce the noise and vibration for high-precision motions. In this paper, an improved PSRM by optimization design for minimization of the electromagnetic force ripple is proposed. The structure, principle, and mathematical model of the PSRM are clarified. Based on Ansoft Maxwell, optimization design of the PSRM is performed by improved structure with smaller pole pitch and incremental number of mover poles. Experiments of the improved PSRM are implemented based on dSPACE. The experimental results verify that the improved PSRM effectively reduces electromagnetic force ripple with planar trajectory tracking. [ABSTRACT FROM AUTHOR]

This paper discusses about the voltage output ripple reduction and error minimization for the direct-drive, linear switched reluctance generator (LSRG)-based wave power generation system. First, the concept of the LSRG-based wave power generation system is studied. According to the characteristics of the LSRG, the suitable drive circuit dedicated to proper current excitation and generation is established. Second, the reasons that cause voltage output ripples are investigated. To reduce the remarkable ripples from phase current commutations, a current distribution function (CDF) is proposed based on the minimized copper loss principle. Third, the dual-loop control strategy with current and voltage as the inner and outer loop is constructed, implemented with the proposed CDF. Theoretical bases of the control strategy are derived. The simulation results prove that the proposed control algorithm is capable of voltage ripple suppression and error reduction within the range of ±0.5 V over the entire operation speed for wave energy extraction, validated by experimental verification. [ABSTRACT FROM AUTHOR]

Mn0·4Zn0·6NdxFe2-xO4/polyaniline (PANI) nanocomposites with magnetic properties were prepared by in situ polymerisation of aniline in the presence of Mn0·4Zn0·6NdxFe2-xO4 nanoparticles. The structure and morphologies of nanocomposites were characterised by X-ray diffraction, Fourier transform infrared (FTIR) spectroscopy and transmission electron microscopy (TEM). X-ray diffraction analysis shows that the size of Mn0·4Zn0·6NdxFe2-xO4 nanocomposites increases with the increase in the Nd doped amount. The optimum doped amount of Nd was 0·075, and the optimum calcination temperature was 850°C. The ferrite particles are well embedded in PANI chains. The FTIR results further prove that the Nd doped manganese-zinc-ferrite/PANI composites have been synthesised. Images (TEM) showed that the nanocomposites presented a spherical structure with a magnetic core of Mn0·4Zn0·6NdxFe2-xO4 and a conducting shell of PANI. The results showed that the electromagnetic properties of the Mn0·4Zn0·6NdxFe2-xO4/PANI composites were related to the mass ratio of PANI, the amount of Nd, the calcination temperature and the precipitation time. [ABSTRACT FROM AUTHOR]

Core loss is one of the key factors for performance evaluation of switched reluctance machines. In this paper, core loss analysis of the planar switched reluctance motor (PSRM) is calculated based on the 3-D time-stepping finite element methods. The numerical analysis for the computation of the core loss is discussed, also its transient and average core loss in the mover and the stator are calculated. The corresponding experiments of measurement loss for a PSRM prototype are conducted and the results validate the accuracy from the numerical analysis. It can be concluded that core loss dominates around the corner of the mover and stator cores. [ABSTRACT FROM AUTHOR]

An integrated rotary–linear machine based on switched reluctance principle is investigated. The characteristics of the motor are analyzed by finite-element methods, with particular emphasis on the coupled magnetic paths. Results from numerical calculation are verified by the hardware experiment. The simple yet effective decoupling algorithm for the independent position control of both rotary and linear axes is proposed. Implemented with the proportional–integral-differential algorithm, the motor is capable of high-precision rotary and linear position tracking with the steady error within 0.3^\circ and 10~\mum, respectively. [ABSTRACT FROM AUTHOR]

A novel double-sided electric asymmetric linear switched reluctance motor (LSRM) is proposed in this paper. The features of the proposed linear machine are that mover teeth and stators are not exactly identical according to the axis of the moving platform. This machine structure ensures that the alleviation of motor saturation magnetization effect and a higher thrust force output can be derived from the asymmetric LSRM. A thorough magnetic analysis is carried out for performance prediction of the machine, and results are compared to a symmetric LSRM counterpart. Both theoretical and finite-element methods results prove the priority of the asymmetric LSRM with higher force-to-volume ratio and better acceleration performance. Experimental results from the machine prototype validate the design of an asymmetric LSRM with yoke length of 12 mm. [ABSTRACT FROM PUBLISHER]

A transverse-flux tubular linear machine with novel gear-shaped teeth for high force density is proposed. The teeth can be formed by silicon steel laminations or permanent magnets for a tubular linear switched reluctance or tubular linear hybrid motor. With the unique improved teeth structure and short magnetic circulation paths, larger propulsion force output can be obtained with reduced mover weight and volume. Simulation based on finite element method (FEM) verifies the validity of the proposed machine design. The proposed machines are compared with other transverse-flux linear machines. Results show that the proposed tubular motors exhibit better output performance with a higher force-to-volume ratio. [ABSTRACT FROM AUTHOR]

An improved force distribution function (FDF) of linear switched reluctance motors (LSRMs) based on nonlinear inductance modeling for force ripple minimization and smooth speed operation is proposed. Nonlinear inductance profile is divided into three segments with a K factor that depicts current effect on inductance of the LSRM. Speed controller based on the proposed FDF and the nonlinear inductance model is constructed. Both simulation and experimental results verify the proposed FDF with the nonlinear inductance modeling effectively reduce force ripples with uniform speed response. [ABSTRACT FROM AUTHOR]

This paper presents a novel two-dimensional (2-D) planar switched reluctance motor (PSRM) for position control applications. The proposed 2-D planar motor has the advantages of simple mechanical construction, high reliability, and the ability to withstand hostile operating conditions. Due to the unique structure of the planar motor's magnetic circuit, there is very little coupling between the X- and Z-axis, and no decoupling compensation is needed. It is expected that this innovative SR planar motion system will be an ideal replacement for traditional X-Y tables in industrial automation applications. [ABSTRACT FROM AUTHOR]

A novel planar motor based on the switched reluctance (SR) principle has been developed. This motor has the advantages of simple structure, low cost and ease of manufacture. The motor is highly reliable and can work in hostile working environments. However, in many industrial applications, the motor's performance is subject to practical constraints, such as mechanical noise, load disturbance and friction. The motor cannot cope with these difficulties under classical PID control scheme. Therefore an auto-disturbance rejection control (ADRC) strategy is proposed to overcome these problems. An ADRC velocity control strategy is implemented on the planar motor, and its performance is then compared with a classical PID controller. Experiment results demonstrate that the motor is more resistant to disturbances under this new control scheme. It confirms that ADRC is an effective solution to overcome the inherent control problems of the SR planar motor. It is expected that the same method can be applied to other SR machines with the same promising results. [ABSTRACT FROM AUTHOR]

A controller design methodology to regulate the output voltage of a phase-shifted resonant converter is presented. The design objective is to overcome the highly nonlinear characteristics of the phase-shifted resonant converter observed when the load is unknown. The control goal is to maintain the output voltage at desired values in the presence of large load perturbations by varying the phase angle of the full-bridge converter. The controller is derived using passivity theory which ensures that the closed-loop system is exponentially convergent and that only a single output feedback is required. An adaptive version is deduced to estimate the output load resistance for the passivity control. This feature allows the use of an extra output current sensor to be avoided. The structure of the controller derived using passivity theory is very simple. Laboratory experiments performed using a digital signal processor system confirm the robustness of the converter with the passivity-based controller. [ABSTRACT FROM AUTHOR]

Superhydrophobic surfaces (SHS) have potential in solving the icing of aircraft, high-voltage overhead transmission lines, and other power network devices exposed to the air. For this reason, we wish to establish the relationship between microstructure and the adhesion work by thermodynamic method, also for analysis of the relationship between the hydrophobicity and icephobicity (or anti-icing). Therefore, respectively considering Cassie-Baxter and Wenzel states, such relationship was theoretically established based on one/two-step surface model, enlightened by natural and artificial SHS. Among it, how to obtain the adhesion work of icing per unit ice-solid interface is the key to this study. Followed by it, hydrothermal experiment, chemical deposition, and etching methods were performed to verify our theoretical results. •How to model for the SHS based on the natural and artificial SHS;•Computation for adhesion work (w aw ) per unit area of a water droplet-SHS interface;•Computation for adhesion work (w ai ) per unit area of a frozen water droplet-SHS interface;•Computation for reduced adhesion work (w a2 ) after icing;•Hydrothermal experiment, chemical deposition and etching methods were used for validation of modeling.

Objective: To investigate the value of intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) in the differential diagnosis and blood perfusion evaluation of benign and malignant hepatic lesions. Methods: A retrospective analysis was performed for 86 patients (96 lesions) with pathologically or clinically confirmed hepatic lesions or hepatic lesions diagnosed based on follow-up results, among whom 48 had malignant lesions (53 lesions) and 38 had benign lesions (43 lesions). The patients underwent conventional magnetic resonance (MR) plain scan, contrast-enhanced scan, and diffusion-weighted imaging (DWI) with different b values (b = 0, 50, 100, 150, 200, 400, 600, 800, 1 000, and 1 200 s/mm 2 ) to determine the parameters of the double exponential model for intravoxel incoherent motion (IVIM): fast diffusion coefficient Dfast, slow diffusion coefficient Dslow, and percentage of fast-diffusion constituent F value. The patients were divided into groups according to the blood supply to lesions on conventional MR plain scan and contrast-enhanced scan, and there were 47 lesions in abundant blood supply group and 49 in poor blood supply group. The data for analysis were Dfast, Dslow, and F values of benign/malignant lesion groups and abundant/poor blood supply groups. The independent samples t-test was used for statistical analysis; the independent samples non-parametric test Mann-Whitney U test was used for the comparison of F value; the receiver operating characteristic (ROC) curve was used to evaluate the value of above parameters in the differentiation of benign and malignant lesions and blood supply evaluation. Results: Compared with the malignant lesion group, the benign lesion group had significantly higher Dslow, and F values ( P < 0.001 or P = 0.001) and a higher Dfast value ( P = 0.053). Compared with the poor blood supply group, the abundant blood supply group had significantly higher Dfast and F values ( P < 0.001 or P = 0.001) and a higher Dslow value ( P = 0.185). According to the ROC curve, the cut-off values of Dslow, Dfast, and F values in the diagnosis of benign/malignant hepatic lesions and evaluation of abundant/poor blood supply were 1.18×10 -3 mm 2 /s, 27.20×10 -3 mm 2 /s, 20.25%, 1.17×10 -3 mm 2 /s, 20.30×10 -3 mm 2 /s, and 17.80%, respectively, with sensitivities, specificities, accuracy, and areas under the ROC curve of 90.69%/92.45%/91.66%/0.938, 46.51%/73.58%/61.45%/0.589, 74.41%/50.94%/62.50%/0.653, 59.57%/57.14%/58.33%/0.559, 55.32%/63.26%/59.37%/0.618, and 93.61%/89.79%/90.62%/0.961, respectively. Conclusion: The parameter of the double exponential model for IVIM, Dslow value, has a certain value in the differential diagnosis of benign and malignant hepatic lesions, and F value can show blood perfusion in benign and malignant hepatic lesions without the need for contrast-enhanced scan, which provides a reference for the qualitative diagnosis of liver tumor.

The design of an X-Y table applying direct-drive linear switched reluctance motor (LSRM) principle is proposed in this paper. The proposed X-Y table has the characteristics of low cost, simple and stable mechanical structure. After the design procedure is introduced, an adaptive position control method based on online parameter identification and pole-placement regulation scheme is developed for the X-Y table. Experimental results prove the feasibility and its priority over a traditional PID controller with better dynamic response, static performance and robustness to disturbances. It is expected that the novel two-dimensional direct-drive system find its applications in high-precision manufacture area., (Copyright © 2012 ISA. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate relationships between dietary macronutrient intakes and glucose tolerance in pregnancy, Research Design and Methods: Nulliparous pregnant Chinese women diagnosed with gestational diabetes mellitus (GDM) (n = 56) were compared to age-, gestational age-, height-, and parity-matched groups with normal glucose tolerance (n = 77) and glucose intolerance (IGT) (n = 38) based on the results of an oral glucose tolerance test (National Diabetes Data Group criteria), performed between 24 and 28 weeks of pregnancy. A 24-h recall dietary assessment was also obtained at the time of screening., Results: Subjects with IGT and GDM were significantly heavier (66.1 +/- 1.4 and 68.6 +/- 1.2 kg, respectively, mean +/- SEM) (P < 0.0001) than the normal group (61.2 +/- 1.8 kg) and had a higher BMI. Overall energy intake was similar between groups, as were the intakes of each macronutrient (%kcal). However, there was a highly significant reduction in polyunsaturated fat intake in the IGT and GDM groups whether expressed as %kcal, % of total fat, or fat kcal. This effect was independent of body weight or BMI whether assessed by ordinal logistic regression or by analysis of a weight- and BMI-matched subgroup of the subjects (P = 0.002 for %kcal; n = 47 normal, 26 IGT, and 43 GDM subjects). In logistic regression analysis of the complete data set, increased body weight (P < 0.0001) and decreased polyunsaturated fat intake (P = 0.0014) were both independent predictors of glucose intolerance (IGT and GDM), as were increased body weight and a low dietary polyunsaturated to saturated fat ratio., Conclusions: Increased polyunsaturated fat intake is associated with a reduced incidence of glucose intolerance during pregnancy. This finding may have major implications for dietary management of women with or at risk of developing GDM.

Thiourea (TU) is a thyroid carcinogen which has previously been shown to cause genotoxicity in various test systems in vitro and in vivo. The mechanism underlying these effects has not yet been elucidated. The present study addressed the question of whether the formation of oxidized products of TU might be involved in genotoxicity. Chemical oxidation of [14C]TU with hydrogen peroxide in the presence of calf thymus DNA resulted in the formation of [14C]formamidine sulfinate ([14C]FASA), [14C]cyanomide, and [14C]urea and in covalent binding of radioactivity to the DNA. Incubation of V79 Chinese hamster cells with 10-20 mM TU for 18 hr but not for 3 hr, increased the frequency of micronuclei to a slight extent. In cells depleted of glutathione, which can prevent the oxidation of TU, micronucleus induction by TU was more pronounced and detectable both after 3 and 18 hr of incubation. Exposure of the cells to 1.25 to 10 mM FASA for 3-5 hr induced micronuclei, DNA repair synthesis, and gene mutations in the cells. Flavin-containing monooxygenase (FMO], an enzyme known to catalyze the S-oxygenation of TU in liver, could not be detected in the postmitochondrial supernatant (S-9) of the V79 cells. There is evidence, however, that TU can easily autoxidize to S-oxygenated products. Both FASA and TU caused a slight induction of DNA repair synthesis in cultured rat hepatocytes, but FASA was active at lower concentrations than TU. Cyanamide did not elicit repair. The finding that FASA, a product of both the nonenzymatic and the enzymatic S-oxygenation of TU, is genotoxic in cultured mammalian cells provides for the first time a hypothesis to explain the genotoxicity of TU.

False-negative results from transthoracic needle aspiration biopsy of malignant lung masses may occur if a central necrotic area is present and is the source of the biopsy material. The purpose of this study is to determine if the use of ultrasonic guidance can improve the sensitivity of lung needle biopsies in this circumstance. Sixty patients with malignant lung masses underwent ultrasonic examination in an 18-month period. In 14 cases, ultrasound showed that the mass had a large central necrotic area that was at least half the diameter of the tumor. Under ultrasonic guidance, needle biopsy specimens were taken from the central necrotic area and from the tumor wall in each case. Adequate biopsy specimens were obtained in all 14 patients. In all cases, the mural biopsy material was diagnostic for malignant tumor, while the biopsy specimen from the necrotic center was nondiagnostic in 10 of 14 patients. No complications occurred. We conclude that ultrasonically guided lung biopsy is a useful and safe tool to avoid false-negative needle biopsy specimens in malignant lung tumors with necrotic centers.

The in vitro effects of ISO on the immune responses of cancer patients were investigated. Forty seven patients with primary tumors (26 lung carcinoma, 14 breast adenocarcinoma, 7 melanoma) were studied. Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, and monocyte chemotaxis were measured. In 40 of the 47 patients (85%), ConA-induced lymphocyte proliferation was depressed; NK activity was depressed in 32 (68%), and monocyte chemotaxis was found to be depressed in 36 (77%). For in vitro studies, an optimum concentration of ISO (100 micrograms/ml per 10(6) cells) was used to treat peripheral blood mononuclear cells. In the presence of ISO, all three parameters were restored to normal or near normal levels in those that were depressed. Under these preincubation conditions in vitro treatment of mononuclear cells from the peripheral blood of normal individuals with ISO had no effect on their activities in the three assays. Similar effects on these three immune parameters were observed when 24 h supernatants obtained from patients' mononuclear cells pretreated with ISO were employed in these assays.

The effects of human osteosarcoma (OS)-specific dialyzable leukocyte extracts (DLE) in hamsters bearing human OS were investigated. The DLE used in this investigation was prepared from rabbits immunized with human osteosarcoma-associated antigens (DLE-OSAA). Tuberculin (DLE-PPD) and control DLE were prepared from rabbits injected with tuberculin or 0.85% NaCl (DLE-NaCl). DLE was administered subcutaneously into inbred hamsters (each injection contained DLE derived from 10(7) rabbit leukocytes). Four groups of animals were studied: group 1, amputation alone; group 2, amputation plus DLE-OSAA; group 3, amputation plus DLE-PPD; group 4, amputation plus DLE-NaCl. Of the DLE-OSAA-treated animals (group 2), 60% were still alive at 300 days postamputation; whereas in animals in groups 1, 3, and 4, all died within 90 days postamputation. In separate experiments, we found that 100% of the animals in groups 1, 3, and 4 developed pulmonary metastases within 30-60 days postamputation, whereas only 20% of the animals in group 2 developed metastases at the same time; indeed 40% of the DLE-OSAA-treated animals were free of metastases in 240-300 days postamputation. Both the leukocyte adherence inhibition assay (LAI) and lymphocyte DNA synthesis assay (LDS) were used to monitor the transfer of antigen-specific cell-mediated immunity in each group of tumor-bearing hamsters. All surviving hamsters in group 2 had high LAI and LDS activity. Our results suggest that DLE-OSAA is effective in preventing pulmonary metastases and death of OS-bearing hamsters (after amputation) as compared with amputation alone, amputation plus DLE-NaCl, and amputation plus DLE-PPD, and that its effect is via an antigen-specific mechanism.

Human lymphoblastoid cell lines that produce specific antibody against human osteosarcoma associated plasma membrane antigens have been established by preselecting OSAA binding human B lymphocytes from an osteosarcoma patient followed by Epstein-Barr virus (EBV) transformation. Four cell lines ( Kla -1, Kla -2, Kla -3, Kla -4) were obtained and cloned. The antibodies were lambda light containing IgM. The specificities of the antibodies were confirmed by immunofluorescence assays using tumor cell lines of various histologic types. Positive immunofluorescence was observed with all human osteosarcoma cell lines tested except one but not with tumor cell lines of other histologic types.

We have investigated the transfer of specific cell-mediated immunity (CMI) to osteosarcoma-associated antigens (OSAA) to hamsters with dialyzable leukocyte extracts (DLE) from OSAA-immunized rabbits. The transfer of specific CMI was determined by leukocyte adherence inhibition (LAI) assay and skin testing. DLE was prepared from rabbits immunized with OSAA, purified protein derivative (PPD), or fibrosarcoma cell plasma membrane preparation (FSM). Control DLE was prepared from rabbits injected with 0.85% NaCl. Significant leukocyte adherence inhibition was observed with leukocytes from hamsters that had received OSAA-specific, PPD-specific, and FSM-specific rabbit DLE, when OSAA, PPD, and FSM were used as antigens, respectively. Similarly, significant ear swelling after injection of OSAA, PPD, or FSM was observed only in hamsters that had received DLE from rabbits immunized with OSAA, PPD, or FSM, respectively. These results suggest that CMI specific for OSAA, PPD, or FSM can be transferred to normal hamsters by DLE from immunized rabbits.

The effects of three selected potential folate antagonists on 3H-leucine incorporation of eight established breast adenocarcinoma cell lines were investigated. The compounds studied were 5,8-dideazaisofolic acid, 5-methyl-5,8-dideazaisofolic acid, and 10-oxa-5,8-dideazafolic acid. All three anti-folates were inhibitory to most of the cells tested. 10-Oxa-5,8-dideazafolic acid was more effective in inhibiting the growth of these tumor cell lines. Both natural killer cell activity and phytohemagglutinin (PHA)-induced lymphocyte proliferation were decreased in hamsters injected with these compounds, with 5,8-dideazaisofolic acid being the most potent in this regard. The natural killer cell activity and lymphocyte proliferation returned to normal levels 12 days post-injection of these compounds. These studies suggest that 10-oxa-5,8-dideazafolic acid may be useful for the treatment of human breast tumors.

The in vitro effects of isoprinosine (ISO) on the immune responses of aging humans were investigated. 64 healthy elderly humans (65 yr of age or over) were included in this study. Four immune parameters were measured, namely, Concanavalin A (ConA)-induced lymphocyte proliferation, natural killer cell (NK) activity, neutrophil chemotaxis, and interleukin-2 (IL-2) production. The ConA-induced lymphocyte proliferation was depressed in 55 of the 64 individuals (85.9%%), while the NK activity was depressed in 41 of the 64 individuals (64%). Neutrophil chemotaxis was depressed in 52 of the 64 individuals (81.1%) and IL-2 production was depressed in 35 of the 64 individuals (54.6%). In the presence of ISO, ConA-induced lymphocyte proliferation, NK activity, neutrophil chemotaxis, and IL-2 production were restored to normal or near normal levels in 50 of the 55 (90.0%), 35 of the 41 (85.3%), 44 of the 52 (84.6%), and 25 of the 35 (71.4%) aging humans, respectively. Our results indicate that ISO acts as an immune potentiator in these in vitro immune assays.