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To circumvent the limitations of using postmortem brain in molecular assays, we used avidin–biotin binding to couple superparamagnetic iron oxide nanoparticles (SPIONs) (15–20 nm) to phosphorothioate-modified oligodeoxynucleotides (sODNs) with sequence complementary to c-fosand β-actinmRNA (SPION-cfos and SPION-βactin, respectively) (14–22 nm). The Stern–Volmer constant for the complex of SPION and fluorescein isothiocyanate (FITC)-sODN is 3.1 × 106/m. We studied the feasibility of using the conjugates forin vivomagnetic resonance imaging (MRI) to monitor gene transcription, and demonstrated that these complexes at 40 μg of Fe per kilogram of body weight were retained at least 1 d after intracerebroventricular infusion into the left ventricle of C57Black6 mice. SPION retention measured by MRI as T2* or R2* maps (R2* = 1/T2*) was compared with histology of iron oxide (Prussian blue) and FITC-labeled sODN. We observed significant reduction in magnetic resonance (MR) T2* signal in the right cortex and striatum; retention of SPION-cfos and SPION-βactin positively correlated with c-fosand β-actinmRNA maps obtained fromin situhybridization. Histological examination showed that intracellular iron oxide and FITC-sODN correlated positively within vivoMR signal reduction. Furthermore, in animals that were administered SPION-cfos and amphetamine (4 mg/kg, i.p.), retention was significantly elevated in the nucleus accumbens, striatum, and medial prefrontal cortex of the forebrain. Control groups that received SPION-cfos and saline or that received a SPION conjugate with a random-sequence probe and amphetamine showed no retention. These results demonstrated that SPION-sODN conjugates can detect active transcriptions of specific mRNA species in living animals with MRI.

We evaluate the accuracy of the Porcelli sawtooth model using more realistic numerical models from the ORBIT‐RF and GATO codes in DIII‐D fast wave heating experiments. Simulation results confirm that the fast wave‐induced energetic trapped particles may stabilize the sawtooth instability. The crucial kinetic stabilizing contribution strongly depends on both the experimentally reconstructed magnetic shear at the q = 1 surface and the calculated poloidal beta of energetic trapped particles inside the q = 1 surface.

Recoil mechanism is an important part of artillery. By pushing the liquid through the throttle at high speed, it can create a resisting force and dissipate the recoil energy. Liquid leaking is the most common fault of it. Because the body case of it is a sealed steel cylinder, liquid leaking will form a vacuum cell in the working chamber. Then this vacuum cell will cause an “effect of supercharging” in it when the artillery firing. This will bring about many disadvantage effects to the artillery, especially to the performance of motive seals. Usually the liquid leaking rate is used to evaluate the seals tightness of the recoil mechanism. However considering the liquid leaking and the “effect of supercharging”, an interesting thing will be found that the liquid leaking rate as the only evaluation criterion becomes not enough.

Purpose: Quantification of the dosimetric impact of the Elekta IGRT treatment couch in different beam field sizes. Established the relationship of relative dose versus beam angle at different beam field sizes. Methods: Measurements of couch attenuation were performed at gantry angles from 180° to 120°, using a 0.125cc semiflex ionization chamber, isocentrically placed in the center of a homogeneous cylindric sliced RW3 phantom for 6 photon beams. Measurements were performed at six different field sizes (3×3, 5×5, 7×7,10×10, 12×12 and 15×15 cm2). The phantom were positioned at the center of the couche,100 MU were delivered at every gantry angle. The dose difference to the ion chamber was determined. Results: For oblique fields with 6 MV photons at the same gantry angle the attenuation coefficient value from the lagest to the smallest the order is field size 7 cm2,5 cm2,10 cm2,12 cm2,15 cm2 and 3 cm2. The biggest couch attenuation by up to 4.15% at the gantry angle of 140°for the field size of 7 cm2, while for the field size of 3 cm2 the couch attenuated value only 3.5%. The other field size couch attenuation values are between the couch attenuated value of field size of 7 cm2 and 3more » cm2 Conclusion: The recommended treatment couch attenuation measured beam field size is 10×10 or 12×12 cm2. When measured using the beam field size 3×3 cm2 the tested value will be lower, while measuerd using the beam field size 7×7 cm2 the tested value will be higer than the recommended beam field size. This should be noted when modeling the treatment couch in the treatment planning system.« less

Bamboo is a typical natural composite material, and its special structure and excellent properties provide important information for the biomimetic design of composites. To strengthen the fiber content of bamboo distributed in a gradient, a bimimetic nano-Al2O3 composite coating was designed and prepared on the surface of metal parts using a nanocomposite electrodeposition method. The optimal technology parameters were obtained, such as current density, PH value, nano-Al2O3 content in electrolyte, and style of stirring etc after the experiments. The microstructure of the biomimetic nanocomposite gradient coating was very dense, and the contents of nano-Al2O3 were distributed in the gradient. The microhardness of the composite coating changed from the surface to the inside in the gradient also. Moreover, the wetting angle between water and composite coating obviously increased and reached 97°at room temperature.

Through evolution over hundreds of millions of years, the natural biomaterials generally have superior microstructure and function to normal material. The surface layer of teeth is enamel, which is the hardest structure in the human body. Enamel as a kind of nanoceramic biomaterial; most of its physical and chemical characteristics are similar to normal ceramics. It is of high hardness and is particularly wear resistance. However, the gray cast iron is one of widely used materials. In the process of casting, surface blowholes and micro-pores, which can’t be seen by the naked eye, are formed in castings because of the solidification shrinkage of alloy and separation of gas dissolving in liquid alloy, which results in the poor property of materials. Therefore, the gray cast iron and nano-Al2O3 were chosen as the substrate and reinforcement in this paper, respectively. A laser cladding method was used to prepare biomimetic nanoceramic surface modification composite materials. The surface property of gray cast iron was largely improved. The process and the factors influencing laser cladding were analysed. The microstructure of the surface modification layer can be divided into a cladding layer, bonding layer and substrate layer, and the formation mechanism of each different layer was researched.

Polyhydroxyalkanoates (PHAs) production was carried out under various C:N ratios. A ratio of 100 resulted best polymer yield. C-source was an important factor in synthesis. For example, as the ratio of valeric acid (C5) to butyric acid (C4) in N-free medium was increased, the mole fraction of HV in the copolymer increased. When soy waste was used as a C-source a copolymer, a high HV mole fraction (HB:HV, 75:25) was produced while when malt waste was used, a much lower HV mole fraction (HB:HV, 90:10) was generated. It was concluded that activated sludge bacteria could be induced to produce PHAs using food wastes as C-sources and this could be the basis for production of biodegradable plastics.

This paper describes an efficient method to perform factorization of DSP transforms based on Taylor Expansion Diagram (TED). It is shown that TED can efficiently represent and manipulate mathematical expressions. We demonstrate that it enables efficient factorization of arithmetic expressions of DSP transforms, resulting in a simplification of the computation.

TTC and INT-electron transport system activity tests were compared for assessing heavy metal inhibition of activated sludge. The median inhibitory concentrations (IC50s) of Cu2+, Zn2+, Cd2+, Hg2+, Ni2+, Pb2+ and Ag+ measured via TTC test were lower than those measured via INT test, which indicates that the INT-electron transport system activity test was less sensitive to heavy metal toxicity than the TTC test. Tested heavy metals brought about similar decrease in TTC-electron transport system activity and COD removal rate, but less decrease in INT-electron transport system activity than COD removal rate, which suggests that the TTC-electron transport system activity is a better parameter for reflecting heavy metal inhibition of activated sludge than INT-electron transport system activity. The ranking of tested heavy metals in order of decreasing toxicity based on TTC test was Hg2+, Cd2+, Cu2+, Ag+, Zn2+, Ni2+ and Pb2+, and the ranking based on INT test was Hg2+, Ag+, Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+.

Start-up of a continuously stirred tank reactor for bio-hydrogen production under different initial organic loading rate (OLR) of 3, 7 and 10 kgCOD/m3 d, respectively, was carried out with sewage sludge as inoculum. Molasses wastewater was used as substrate and hydraulic retention time was kept at 6 h. This study aimed to assess OLR on the formation of fermentation types and the structure of microbial communities during the start-up period. It was found that at an initial OLR of 7 kgCOD/m3 d and an initial biomass of 6.24 gVSS/L, an equilibrial microbial community of ethanol-type fermentation could be established within 30 days. The observed average specific hydrogen production rate was 276 mLH2/gVSS d, which was 40% higher than that of the one acclimated with 3 kgCOD/m3 d. Based on denaturing gradient gel electrophoresis profiles, significant microbial population shifts took place at the first 15 days, but a longer period up to 30 days was required to establish a microbial community with stable metabolic activity.

A series of iron(III)-metal-porphyrin dimers linked with flexible alkoxyl chain at para position of two phenyl rings have been synthesized and characterized. An equilibrium of two conformations of porphyrin dimers (open and closed) has been studied by visible spectra. The intensity of absorption band 680 nm relates to equilibrium of two conformations. With the increase of the length of the alkoxyl chain,the closed conformation forms more easily. With the addition of axial ligand, the ferric ion of the dimers tends to bind with imidazole, and the intensity of the band 680 nm gradually decreases and disappears.

This paper presents an algorithm for variable ordering for Taylor Expansion Diagrams (TEDs). First we prove that the function implemented by the TED is independent of the order of its variables, and then that swapping of two adjacent variables in a TED is a local permutation similar to that in BDD. These two properties allow us to construct an algorithm to swap variables locally without affecting the entire TED. The proposed algorithm can be used to perform dynamic reordering, such as sifting or window permutation. We also propose a static ordering that can help reduce the permutation space and speed up the search of an optimal variable order for TEDs.

The value of the mutual diffusion coefficient DV of two acrylic monomers is determined with nuclear microprobe measurements on a set of polymer films. These films have been prepared by allowing the monomers to diffuse into each other for a certain time and subsequently applying fast ultraviolet photo-polymerization, which freezes the concentration profile. The monomer diffusion profiles are studied with a scanning 2.1 MeV proton microprobe. Each monomer contains a marker element, e.g., Cl and Si, which are easily detected with proton induced x-ray emission. From the diffusion profiles, it is possible to determine the mutual diffusion coefficient. The mutual diffusion coefficient is dependent of concentration, which is concluded from the asymmetry in the Cl- and Si-profiles. A linear dependence of the mutual diffusion coefficient on the composition is used as a first order approximation. The best fits are obtained for a value of b=(0.38+/-0.15), which is the ratio of the diffusion coefficient of 1,3-bis(3-methacryloxypropyl)-1, 1,3,3-tetramethyldisiloxane in pure 2-chloroethyl acrylate and the diffusion coefficient of 2-chloroethyl acrylate in pure 1,3-bis(3-methacryloxypropyl)-1,1,3,3-tetramethyldisiloxane. Under the assumption of a linear dependence of the mutual diffusion coefficient DV on monomer composition, it follows that DV = (2.9+/-0.6)10(-10) m(2)/s at a 1:1 monomer ratio. With Flory-Huggins expressions for the monomer chemical potentials, one can derive approximate values for the individual monomer diffusion coefficients.

A Controllable and Observable Protein Crystallization Facility (ACOP) was developed in 1999 for space experiment in the Get Away Special canister of Space Shuttle. To regulate the vapor diffusion rate, in a crystallization chamber, five cells each containing precipitant solution of different concentrations, exposed to one protein cell in turn. Five layers of chambers were overlapped coaxially. The crystallization process was observed and recorded by digital cameras. Structure of facility and result of image sequence were given.

To evaluate a single step electrophoresis for quantitative determination of cholesterol of high-, low-, very-low-density lipoprotein(HDL, LDL, VLDL) and fast pre-beta lipoprotein [lipoprotein (a), Lp(a)].Quantification of lipoprotein cholesterol was performed by enzymatic staining of cholesterol in a new agarose gel electrophoresis method that allows the separation of LDL, VLDL, HDL, and Lp(a) by Helena REP system. The results of electrophoresis method were compared with those by traditional method like PTA-Mg2+ precipitation method for HDL-C, PVS precipitation method for LDL-C, and Immunoturbidimetric assay(ITA) method for Lp(a).Within-runs CV were 5.16%-7.46%, 1.26%-3.28% and 3.78%-5.86% for VLDL-C, LDL-C and HDL-C, respectively. Between-runs CV were 8.35%-11.25%, 2.78%-4.08% and 4.23%-6.36%, respectively. The linearity of this method was up to 10.35 mmol/L total cholesterol. The recoveries were 90.3%, 94.3% and 89.6%, respectively. No interference were observed when bilirubin(342 mumol/L), hemoglobin(20 g/L) or triglyceride(11.0 mmol/L) were added to pooled serum, respectively. There was good agreement between methods, with r = 0.9557 for HDL-C(electrophoresis method vs PTA-Mg2+ precipitation method), r = 0.9609 for LDL-C(electrophoresis method vs PVS precipitation method) and r = 0.9235 for Lp(a)-C (electrophoresis method) vs Lp(a) (ITA method).The electrophoresis method offers a simple and inexpensive means of simultaneously measuring HDL-C, VLDL-C, Lp(a)-C and LDL-C.

To investigate the factors that influence the consistency of international normalized ratio (INR) of prothrombin time.Using the same automated blood coagulation analyzer and INR calibration plasma with two different types of prothrombin time (PT) reagent to assay the INR values of 19 controls (group 1), 12 patients who took long-term anticoagulant orally (group 2), 12 patients who took it at the first time (group 3) and 8 patients who took long-term anticoagulant together with cephalosporin N (group 4).The two kinds of reagents gave quite different INR values in all four groups (P0.01). The INR difference in group 3 (0.23 +/- 0.07, n = 12) was larger than that in group 2 (0.51 +/- 0.20, n = 12) (P0.01). The difference in group 4 (0.61 +/- 0.21, n = 8) was larger than that in group 2 (P0.01).The factors that may influence INR consistency are the source and sensitivity of the reagents, as well as the period of the anti coagulant been taken and the other drugs taken at the same time.

A new instrument for observing blood cell state and the process of variation on hemorrheology has been developed. There are three ways of shear rate: setting by hand, automatically setting and simulating pulsative state. It can provide different variable flow fields. The shear rate can be set in the range from 0.1 to 1000 s-1. It needs only a little blood. It can be easyly and rapidely operated. it has clear images. The hemorrheology state of blood cells can be directly perceived through thd instrument by eyes. The display and measurement and record of blood cell's hemorrheology state can be finished in real time dynamically and simultaneously.

In wide-area broadband networks, the intelligence and advanced functionality should reside at the network edge. The switches within the core of the network must be able to switch traffic at high speeds, but do not require the ability to perform sophisticated processing. In this paper, we describe the design of ARC-LITE, an edge switch-routing node that provides ATM/IP processing and advanced quality-of-service features. We explain why ARC-LITE is a revolutionary advance in switch-router technology and how it can be used to enhance the performance and functionality of ATM networks.

Determine and compare the contents of ten trace elements in crude E. acuminatum and its three different processed products.Using flame atomic absorption spectrometry.The ten trace elements were found in both the crude drug and its three processed products, and in terms of contents some of the trace elements in all the three processed products are higher than those in the crude drug.According to the trace element contents, the three processed products of E. acuminatum have their own advantages. It is thus suggested that thoroughgoing clinical and experimental researches be performed anew for the long-shelved processing methods.

The imminent prediction on a group of strong earthquakes that occurred in Xinjiang, China in April 1997 is introduced in detail. The prediction was made on the basis of comprehensive analyses on the results obtained by multiple innovative methods including measurements of crustal stress, observation of infrasonic wave in an ultra low frequency range, and recording of abnormal behavior of certain animals. Other successful examples of prediction are also enumerated. The statistics shows that above 40% of 20 total predictions jointly presented by J. Z. Li, Z. Q. Ren and others since 1995 can be regarded as effective. With the above methods, precursors of almost every strong earthquake around the world that occurred in recent years were recorded in our laboratory. However, the physical mechanisms of the observed precursors are yet impossible to explain at this stage.

A multi-dimensional diffusion model is introduced to characterize the "on-off" sources behavior in an asynchronous transfer mode (ATM) statistical multiplexer, where multiple types of traffic are concentrated. Under a reasonable set of assumptions, this diffusion process can then be approximated by a multi-dimensional Ornstein-Uhlenbeck process, which is a Gaussian Markov process. The packet arrival process is shown to be a Gaussian (but not Markov) process, and this process determines the statistical behavior of the buffer content. An expression is derived for the joint probability distribution of the buffer content and "on-off" sources in the equilibrium state. The final solution form is given in terms of the eigenfunctions of Weber's equation. >

The authors introduce a diffusion model to characterize approximately a statistical multiplexer for a heterogeneous set of traffic sources, which is a basis for ATM (asynchronous transfer mode) fast packet switching in the future B-ISDN (Broadband Integrated Services Digital Networks). Under a reasonable set of assumptions, this diffusion process can then be approximated by a multi-dimensional Ornstein-Uhlenbeck process, which is a Gaussian Markov process. The packet arrival process is shown to be a Gaussian (but not Markov) process, which adequately captures the correlated nature of packet arrivals and determines the statistical behavior of the buffer content. Analytical results are applied to evaluate the multiplexer's dynamic behavior, i.e., the transient packet loss probabilities at the cell and burst levels.

Due to increased demand for channel capacity and reliable service requirement in future wireless communications, dynamic channel allocation (DCA) has been proposed for new calls as well as hand-off calls. We compare the performance of three different DCA algorithms through a detailed simulation, which faithfully captures the dynamics of mobile movements and signal propagation effects. Based on the measurements of signal-to-interference ratios (SIR), our DCA algorithm is intended to improve the system performance in terms of reduced call blocking and dropping rates. We develop a centralized re-packing procedure to optimize the system performance, i.e., to maximize the minimum SIR of all the calls in progress. This optimization problem, which turns out to be an integer non-linear program, is solved by an efficient heuristic algorithm. Our simulation results show that the re-packing procedure embedded in the DCA algorithm can improve the quality-of-service for the system, i.e., the call dropping rate can be substantially reduced for each user.

We investigated the temporal expression of the neural cell adhesion molecule, neurotrimin, in the rat cerebellum and the brainstem from birth to adulthood using immunoreactive labeling. A wave of expression accompanied the development of projection pathways extending from brainstem nuclei (pons/inferior olive) through the cerebellar peduncles into the arbor vitae and disappeared with myelination by P14. Immuno-EM revealed expression of neurotrimin on the surface of unmyelinated axons but not on astrocytes or oligodendroglia. With the development of the molecular and internal granular layers, intense labeling occurred on the surface of parallel fiber bundles, granule cells and mossy fibers. With synaptogenesis, each excitatory junction was labeled by the immunoreaction. By P21, neurotrimin reactivity decreased on the surfaces of neuronal somata, dendrites and axons but remained at excitatory synaptic contact sites in both the molecular and granular layers. The spatial-temporal expression pattern of neurotrimin suggests that this adhesion molecule plays a role in axonal fasciculation of specific cerebellar systems and may also be involved in the formation of excitatory synapses and their stabilization into adulthood.

To explore the mechanism of Jiaweiyiguanjian decoction in nourishing the liver and kidney.A rat model with Yin-deficiency of liver and kidney was made by way of slow irritation. Thyrotropin-releasing-hormone(TRH) of thyron and blood, TSH of pituitary and blood, thyroxine, 3,5,3',5-tetraiodothyronine(FT4) and 3,3',5-traiodothyronine(FT4), 3,3',5-traiodothyronine(rT3) were used as indexes to study the effect of the decoction on HPT.The TRH Secretion from hypothalamus increased (P0.05), TSH of pituitary and blood reduced(P0.05), FT3 and FT4 of blood decreased at the same time and rT3 of blood, increased. The indexes of the treatment group were found almost the same as the those of the normal control group.Jiaweiyiguanjian Decoction could adjust HPT.

To evaluate what kind of patients was at high risk on peritoneal dialysis (PD) treatment.96 patients on PD for (23.1 +/- 10.0) months were studied. The patients were divided into two groups. Group A: patients (25) who died or switched to hemodialysis because of cardiovascular disease, malnutrition, ultrafiltration inefficiency, hydrothora, relapsing peritonitis, etc. Group B: stable PD patients (71) up to now. Age, body surface area (BSA) and dialysate fill volume (DV) were not different between the two groups. The nutritional status, dialysis adequacy, peritoneal membrane transport characteristics, and residual renal function (RRF) in the initial month of dialysis were compared. Patient survival rate was studied by Kaplan-Meier method.It was demonstrated that Kt/V and Ccr in group A were lower than those in group B (P0.05). Meanwhile, RRF was significantly different between the two groups; patients with better RRF (or = 2 ml/min) had higher survival. The percentage of high transporters in group A was greater than in group B.Higher clearance in the initial month of dialysis seems to keep PD successful. PD failure maybe related to high transport characteristic and its treatment modality is DAPD. Hemodialysis will be a better choice when RRF is very low as water balance is poorly controlled by DAPD.

Objectives To evaluate the efficacy and safety of leflunomide in treating lupus nephritis (LN). Methods According to the requirements of meta-analysis, a literature search about efficacy and safety of leflunomide therapy in LN was performed among Cochrane clinical controlled trials database, PubMed, BMJ-Clinical Evidence, CNKI, VIP and Wanfang data from the establishment of the database till December 2010.All included RCTs were graded in term of randomization, allocation concealment and blinding and non-RCTs were graded in term of grouping method, blinding, withdrawal and loss of follow-up, baseline comparability, diagnostic criteria and bias control. RevMan 5.0 software was used for meta-analysis. Results A total of 828 literatures were included. Five RCTs and 2 non-RCTs were enrolled for meta-analysis. Four RCTs described the method of random allocation, 1 literature used double blind method. Five RCTs were all lack of information about allocation concealment, selectively reporting and other bias, but reported withdrawal and loss of subjects. Two non-RCTs were lack of grouping method and blinding, but reported withdrawal and loss of subjects, also used established diagnostic criteria. Leflunomide group was treated with leflunomide and glucocorticoid, while control group was given cyclophosphamide and glucocorticoid or placebo. 1. There was no significant difference in complete remission rate (OR=1.51, 95%CI: 0.90-2.54), partial remission rate (OR=1.06, 95%CI: 0.70-1.61) or overall remission (OR=1.63, 95%CI: 0.98-2.71) between leflunomide group and cyclophosphamide group. 2. The 24 h urine protein, SCr and SLEDAI scores of leflunomide group were significantly lower than that of cyclophosphamide group. There was no significant difference in C3,positive rate of anti-ds DNA between leflunomide group and cyclophosphamide group. 3. There was no significant difference in infection, herpes zoster,hypertension, palpitations, leukopenia, alopecial, elevation in ALT, memoxenia, rashes, or the incidence of gastrointestinal reactions between the two groups. Conclusions Based on the current evidence, the efficacy and safety of leflunomide for treatment of LN are close to cyclophosphamide. Further evidence from RCT studies is needed to elucidate the efficacy and safety of leflunomide for LN. Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.5566

The response of adult T-cell leukemia (ATL) to chemotherapy is poor, and a major obstacle to successful treatment is intrinsic or acquired drug resistance. To determine the clinical significance of multidrug resistance protein (MRP) 1 in ATL, we studied MRP1 expression and its association with clinical outcome. The expression of MRP1 mRNA in leukemia cells from 48 ATL patients was studied by slot blot analysis. The expression level of MRP1 mRNA in chronic-type ATL was significantly higher than that in lymphoma-type ATL (P = 0.033). There was no correlation between MRP1 expression and age, gender, WBC count, LDH, hypercalcemia, blood urea nitrogen, or performance status. However, the expression of MRP1 mRNA correlated only with peripheral blood abnormal lymphocyte counts (P = 0.008). The transporting activity of MRP1 was assessed using membrane vesicles. Membrane vesicles prepared from ATL cells with high expression of MRP1 mRNA showed a higher ATP-dependent leukotriene C(4) uptake than did those with low expression of MRP1 mRNA. This uptake was almost completely inhibited by LTD(4) antagonists ONO-1078 and MK571. In acute- and lymphoma-type ATL, high expression of MRP1 mRNA at diagnosis correlated with shorter survival, and Cox regression analysis revealed that MRP1 expression was an independent prognostic factor. These findings suggest that functionally active MRP1 is expressed in some ATL cells and that it is involved in drug resistance and has a possible causal relationship with poor prognosis in ATL. Multidrug resistance-reversing agents, such as ONO-1078 and MK571, that directly interact and inhibit the transporting activity of MRP1 may be useful for treating ATL patients.

To observe renal damage due to acute hypobaric hypoxia.Thirty-six male wistar rats were randomly divided into three groups A, B and C (n = 12 for each). Group A served as control, while groups B and C were exposed to 5000 m altitude for 30 min. Sample of serum and renal tissues were taken from group B rats 20 min and from group C rats 24 h after the exposure respectively.Serum ureanitrogen (BUN) and creatinine (Crea) increased significantly in group B and C rats after exposure to hypoxia (P0.01). Cl- and alkaline phosphatase (AKP) in serum also increased (P0.05), but renal endothelin (ET) decreased significantly (P0.01). All changes in group C rats tended to recover to normal level, except Cl- which continued to increase. Dilation of renal vessels was found under optic-microscope, and pathological changes were found in mitochondra and epithelial cells.Acute hypobaric hypoxia might be harmful to renal function and structure.

To observe the specitic property of Glomeoular Filtration Rate (GFR) and its relation to endothelin of plasma in pilots.GFR was assessed with single photon emisson computed tomography (SPECT), tracer for 99mTc-DTPA, enthlion of plasma were measured by radio immunossay in forty-six pilots, thirty ground crew and renal disease patients.Endothelin were not correlation with GFR in pilots. GFR of pilots and ground crew had not a significant difference. Compared with ground crew and pilots, endothelin of renal disease patients had a significant increased, and GFR had a significant decreased. Age were a linear negative correlation with total GFR r = (0.84, P0.01), flying time, age had not correlation with endothelin. After thirty-one ground endothelin had a significant difference with ground crew.It suggested that the endothelin has no influence on GFR in pilots when it was increased with in the limits of a level, pilots and ground crew may use the same stand on GFR.

During myelinogenesis, we found an exceedingly strong, transient expression of the alpha(1E) gene for the R-type voltage-gated calcium channel in CNS white matter. This immunoreactivity appeared in glial cells along specific pathways of the brainstem, cerebellum, and telencephalon. The reactivity followed a wave that progressed from the brainstem at P5, to the cerebellar peduncles by P8, the arbor vitae by P14, and the granular layer by P17. The reactivity-peaked about 3-4 days later and decreased gradually to become negligible in all areas before adulthood. Ultrastructural analysis confirmed that alpha(1E) immunoreactivity was located in oligodendroglial somata, their projections, paranodal wraps and loose myelin sheaths. There was a distinct association of the channel protein reactivity on oligodendroglial membranes in contact with the axon. We propose that glial projections, contacting axons, sense axonal firing through small K(+) currents and open the high voltage R-type calcium channels to signal myelination.

After the master cell stock(mcs) and working cell bank of more than 30 different strains of 7 animal kidney cell lines (F-81 or CRFK cell line, MDCK cell line, Vero or Vero-2 cell line, MA-104 cell line and BHK-21 cell line) were established in China, the chromosomal number variations and structural aberrations of the above lines, primary feline or canine kidney cell (FKC or CKC) and HeLa cell line were investigated and their karyotypes of routine or Giemsa chromosomal bands were analyzed. The carcinogenesis or tumorigenicity testing of these cells in about 700 nude mice and for colony formation in soft agar (SA) and for agglutination under different concentration of plant lectins was carried out. Both tumorigenicity-negative strains of F-81, CRFK, Vero or Vero-2 lines and very-low-tumorigenicity strains of MDCK line were successfully selected and evaluated for the production of canine or feline combination viral vaccines, which are free of infectious agents, and described with respect to cytogenetic characteristics and tumorigenicity. Rate of modal chromosome number represents the ratio of cell number having modal chromosome number to all the split cell number analyzed at random. Rate of difference represents the ratio of difference of the rate of modal chromosome number between mcs (master cell stock) + n and mcs passages. The chromosomal analysis results showed that the ratio of difference of the rate of modal chromosome number between mcs + n and mcs passages was not more than 5%-15% and the structure aberrations was generally 0%-3%, not more than 5%-10%, thus the hereditary character of cell lines is comparatively stable without significant difference between different passages. The genetic characteristics of chromosomal number of cell lines determines their tumorigenicity, but it is species specific. Experimental models were established for the researches on the prevention and prophylaxis of malignant tumors or cancers and their genetically biological characteristics. Tests showed that there was correlation among cell line chromosome number variations, anchorage independence in soft agar, agglutination under plant lectins and tumor-forming ability in nude mice. Since testing in vitro is more economic, simpler, faster, and is thought to be reliable, we recommend plant lectins followed by SA or analysis of karyotypes as the initial means for monitoring tumorigenicity of animal cell line in nude mice.

We report the first case of hard metal lung disease in Singapore and the occupational investigative work and control measures that were undertaken.A 38-year-old machinist in the tool manufacturing industry presented with exertional dyspnoea and cough. Chest X-ray revealed bilateral reticulonodular infiltrates with honeycombing. High resolution computed tomography scan of the thorax confirmed the presence of interstitial fibrosis. Open biopsy of the lung showed features of pneumoconiosis. Particle induced X-ray emission (PIXE) analysis, a relatively new elemental analysis technique, performed on the lung biopsy specimen confirmed the presence of tungsten and titanium; and he was diagnosed to have hard metal lung disease. Microbiologic, serologic and histologic investigations excluded an infective cause. Serial pulmonary function tests on follow-up showed no progression. He presented with haemoptysis 10 months later and was diagnosed to have tuberculosis on the basis of positive sputum and bronchoalveolar lavage cultures for Mycobacterium tuberculosis complex.Preventive measures and permanent transfer to non-cobalt work were instituted.The interstitial fibrosis appears to have stabilised.The diagnosis of hard metal lung disease must be considered in a worker exposed to cobalt presenting with interstitial fibrosis.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent lung carcinogens in animals. UGT-mediated O-glucuronidation of NNAL is an important detoxification pathway for these carcinogens. To better characterize this pathway in humans, we screened a series of UGT-overexpressing cell lines and baculosome preparations for their ability to O-glucuronidate NNAL and examined multiple human liver and lung specimens for NNAL-glucuronidating activity and their levels of expression of NNAL-glucuronidating UGTs. Human liver microsomal fractions exhibited significant levels of NNAL-glucuronidating activity, with the NNAL-Gluc II diastereomer formed at a rate 3.4 times that observed for NNAL-Gluc I. As with liver microsomal fractions, NNAL-Gluc II was the major diastereomer formed by homogenates from UGT2B7-overexpressing HK293 cells or UGT2B7-overexpressing baculosomes; the major diastereomer formed by homogenates from UGT1A9-overexpressing V79 cells was NNAL-Gluc I. No significant O-glucuronidating activity of NNAL was detected in UGT1A1-, UGT1A4-, UGT1A6-, UGT2B4-, or UGT2B15-overexpressing HK293 or V79 cell homogenates, or in UGT1A1-, UGT1A3-, UGT1A7-, or UGT1A10-overexpressing baculosomes. Significant levels of UGT2B7 mRNA were detected by reverse transcriptase-polymerase chain reaction in human liver and at low levels in human lung specimens. UGT1A9 mRNA was detected in liver but not in lung. These results suggest that although both UGT2B7 and UGT1A9 play an important role in the overall glucuronidation of NNAL in humans, UGT2B7 potentially plays an important role in the detoxification of NNAL in the lung.

Knowledge of the complete genomic DNA sequence of an organism allows a systematic approach to defining its genetic components. The genomic sequence provides access to the complete structures of all genes, including those without known function, their control elements, and, by inference, the proteins they encode, as well as all other biologically important sequences. Furthermore, the sequence is a rich and permanent source of information for the design of further biological studies of the organism and for the study of evolution through cross-species sequence comparison. The power of this approach has been amply demonstrated by the determination of the sequences of a number of microbial and model organisms. The next step is to obtain the complete sequence of the entire human genome. Here we report the sequence of the euchromatic part of human chromosome 22. The sequence obtained consists of 12 contiguous segments spanning 33.4 megabases, contains at least 545 genes and 134 pseudogenes, and provides the first view of the complex chromosomal landscapes that will be found in the rest of the genome.

4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone and its major metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), are potent lung carcinogens in animals. UDP-glucuronosyltransferase (UGT)-mediated glucuronidation of NNAL is a potentially important detoxification pathway for these carcinogens. To identify the UGT isozyme(s) involved in this pathway, we examined the glucuronidation of NNAL in rat liver microsomes and homogenates from cell lines overexpressing specific UGT isozymes. NNAL glucuronidation was induced in liver microsomes from rats treated with family 2 UGT inducers including phenobarbitol and 3, 5-di-tert-butyl-4-hydroxytoluene, which exhibited 1.7- and 2.6-fold higher rates of glucuronidation than microsomes from control rats. The rates of NNAL glucuronidation in liver microsomes from GUNN (deficient in family 1 UGTs) and RHA parental control rats were similar. All rat liver microsomes used in the present study catalyzed the glucuronidation of (S)-NNAL at a rate between 3.5 and 5.5 times that of the glucuronidation of (R)-NNAL. Liver microsomes from Wistar rats exhibiting the low-androsterone glucuronidation phenotype characteristic of the UGT2B2-deficient genotype glucuronidated NNAL at a rate similar to microsomes from Wistar rats exhibiting the high-androsterone glucuronidation phenotype/UGT2B2 [+] genotype. Homogenates from UGT2B1-overexpressing cells catalyzed the glucuronidation of NNAL at a K(m) of 745 microM. As with rat liver microsomes, NNAL-Gluc I was the major diastereomer formed by UGT2B1. Glucuronidation of NNAL was not detected with homogenates from UGT2B12-overexpressing cells. These results suggest that UGT2B1 plays an important role in the glucuronidation of NNAL in the rat.

The combined cytotoxic effects of the antimetabolites gemcitabine (dFdCyd) and 5-fluoro-2'-deoxyuridine (FdUrd) were studied. Cytotoxicity, biochemical perturbations, and DNA damage seen with dFdCyd and FdUrd alone and in combination were evaluated in HT-29 human colon cancer cells. A 4-h exposure to dFdCyd followed by FdUrd for 24 h produced more than additive cytotoxicity and marked S-phase accumulation. Cells progressed through the cell cycle, however, after a 22-h drug-free interval. [3H]dFdCyd was rapidly metabolized to the 5'-triphosphate and incorporated into DNA. [3H]FdUrd was anabolized exclusively to FdUrd monophosphate, and preexposure to dFdCyd did not affect FdUrd monophosphate formation. Thymidylate synthase catalytic activity was inhibited by 48% after a 4-h exposure to 10 nM FdUrd and by 80% after exposure to the combination. Sequential 4-h exposures to 15 nM dFdCyd and 10 nM FdUrd led to greater depletion of dTTP pools (29% of control) than with either drug alone. Greater effects on nascent DNA integrity were seen with sequential dFdCyd followed by FdUrd. Although parental DNA damage was not evident immediately after exposure to 15 nM dFdCyd for 4 h followed by 10 nM FdUrd for 24 h, high molecular mass DNA fragmentation was evident 72-96 h after drug removal. Sequential dFdCyd/FdUrd was associated with prominent disturbance of the cell cycle, dTTP pool depletion, dATP/dTTP imbalance, and nascent DNA damage. Induction of double-strand parental DNA damage and cell death was delayed, consistent with postmitotic apoptosis.

Because interferons (IFN)-alpha and -gamma individually have increased fluorouracil (FUra) cytotoxicity in several in vitro models, we studied the effects of FUra combined with IFN-alpha + gamma in HT29 colon cancer cells. A 96-hr exposure to IFN-alpha (500 units/ml) plus IFN-gamma (10 units/ml) and a 72-hr exposure to 0. 25-1 microM FUra (hr 24-96) inhibited cell growth and colony formation in an additive or more-than-additive fashion. When cells were exposed to IFN-alpha + gamma and FUra, free FdUMP levels became detectable, whereas [3H]FUra-RNA incorporation decreased. Exposure to IFN-alpha + gamma, FUra, or the combination decreased dTTP pools to 58%, 43%, and 17% of control, respectively. A marked increase in the dATP to dTTP ratio was seen with FUra with or without IFN-alpha + gamma. Thymidylate synthase catalytic activity was reduced to 28% and 24% of control with FUra with or without IFN-alpha + gamma, suggesting that the enhanced dTTP depletion must be due to another mechanism. FUra-mediated thymidylate synthase inhibition was accompanied by a 124-fold increase in total deoxyuridylate immunoreactivity and a 31-fold increase in dUTP pools, but the addition of IFN-alpha + gamma attenuated the accumulation. Treatment with IFN-alpha + gamma and FUra individually interfered with nascent DNA chain elongation, whereas the three-drug combination produced the most striking effects. IFN-alpha + gamma plus FUra produced the greatest amount of single-strand breaks in nascent DNA and dramatically decreased net DNA synthesis. IFN-alpha + gamma with or without FUra produced double-strand breaks in parental DNA. These results suggest that dTTP depletion, dATP/dTTP imbalance, pronounced inhibition of DNA synthesis, and damage to nascent and parental DNA contribute to the enhanced cytotoxicity with the triple combination.

Insulin-like growth factor-II (IGF-II) is thought to play a critical role in the development of embryonic tumors such as Wilms' tumor. However, despite highly elevated IGF-II mRNA levels in tumors, IGF-II is not elevated in the serum of patients with Wilms' tumors. Recently high molecular weight forms of IGF-II ('big'- or pro-IGF-II) have been found to be produced by some tumors. In order to prove whether or not high molecular weight forms of IGF-II are produced by Wilms' tumor cells and secreted into the culture medium, we established Wilms' tumor cell lines. After column chromatography of the culture medium, IGF-II and pro-IGF-II concentrations were measured. For pro-IGF-II measurement we established a pro-IGF-II RIA using a rabbit polyclonal antiserum directed against amino acids 7-21 (E7-21) of the E-domain of pro-IGF-II. Gel electrophoresis and Western blotting with anti-IGF-II antibodies revealed a band at 7.5 kDa corresponding to fully processed IGF-II and bands between 10 and 20 kDa. Using pro-IGF-II antiserum, bands between 10 and 25 kDa were detected. We conclude that in vitro cultured Wilms' tumor cells produce and release various forms of 'big IGF-II' with molecular masses between 10 and 25 kDa. It remains uncertain whether these high molecular weight forms of IGF-II represent normal precursors of IGF-II or incorrectly processed IGF-II.

The importance of both the CYP1A1 exon 7 (ile:val) and GSTM1 (0/0) polymorphisms in oral cancer susceptibility was assessed by examining polymorphic prevalences in 135 patients with oral cancer and 135 noncancer controls frequency-matched by age at diagnosis (+/- 5 years), race, sex, and institute of patient recruitment. The prevalence of the GSTM1 (0/0) genotype was approximately 51% in both cases and controls. The prevalence of the CYP1A1 (ile:val) polymorphism [including both the (ile/val) and (val/val) genotypes] was significantly higher in cases as compared to controls (17.6% versus 7.6%, respectively; crude odds ratio, 2.6; confidence interval, 1.2-5.7). No association was observed between polymorphic prevalence and levels of smoking or alcohol consumption in cases. These results suggest that the GSTM1 null genotype is not associated with oral cancer risk. These results also suggest that individuals with the CYP1A1 exon 7 ile:val polymorphism are at increased risk for oral cancer, and that this risk may not be influenced by differences in exposure to tobacco smoke.

This paper reports a method for determination of low molecular weight aldehydes in polluted air by GC-FID using a GDX-401 packed column (3 mm x 3 m). The advantages of this method are simple, rapid, accurate and sensitive. The method requires only 8 minutes for the whole analysis. In the concentration range of 1.7-442.4 mg/m3 for formaldehyde and 0.5-680 mg/m3 for acetaldehyde and propionaldehyde the calibration curves are linear. The minimun detectable amounts are 3.5 ng, 1 ng and 1 ng, and the average recoveries (n=5) are 89.4%, 89.6%, 88.1% for formaldehyde, acetaldehyde and propionaldehyde respectively. The quantitative determination is performed by external standard calibration method. The results of sample analysis are satisfactory.

Theophylline, phenobarbital, amobarbital and carbamazepine are the chief therapeutic drugs in clinical practice. Because of the differences among inter-individuals in the metabolic clearance of these drugs and their toxicity at certain levels of concentration in serum, the dosage should be regulated to maintain a therapeutic blood drugs level. To achieve this a rapid and accurate assay method for drugs in blood is necessary. This paper reports that a reversed phase high performance liquid chromatographic (HPLC) method had been established for the simultaneous separation and quantitative determination of the four drugs in serum. The separation was performed on RP-C18 column using methanol:water (1:1) as mobile phase and 4-aminoantipyrime as internal standard. The eluted substances were detected at 210nm.

To explore the determinants of cytotoxicity during prolonged exposure to pharmacologically relevant concentrations of 5-fluorouracil (FUra), we studied the effects of FUra at concentrations ranging from 0.1 to 1 microM in HCT 116 and HT 29 colon cancer cells grown in the presence of physiologic levels of leucovorin. A 5- and 7-day exposure to 1 microM FUra reduced cell growth to 46% and 20% of control in HT 29 cells and to 74% and 38% of control in HCT 116 cells. Concurrent exposure to thymidine (10 or 20 microM) or uridine (1 mM) provided partial protection against FUra toxicity in HT 29 cells, but did not protect HCT 116 cells. After a 24-h exposure to 1 microM [3H]FUra, free 5-fluoro-2'-deoxyuridine-5' -monophosphate (FdUMP) and FUDP. + FUTP levels were 0.7 and 144 pmol/10(6) cells in HT 29 cells, respectively, and 3.9 and 178 pmol/10(6) cells in HCT 116 cells. FdUMP and FUDP + FUTP pools increased by 5.7- and 2.0-fold in HT 29 cells and by 1.7- and 3.3-fold in HCT 116 cells over the next 48 h, but did not accumulate thereafter. After a 24-h exposure to 1 microM [3H]FUra, FUra-RNA levels were 158 and 280 fmol/microgram in HT 29 and HCT 116 cells, respectively; FUra-RNA levels increased over time, and reached 700 and 1156 fmol/microgram at day 5. Concurrent exposure to 1 mM uridine for 72 h did not diminish [3H]FUra-RNA incorporation. Upon removal of [3H]FUra following a 24-h exposure, FUra-RNA levels remained relatively stable with 57-78% retained at 120 h. A low level of [3H]FUra-DNA incorporation was detected in HT 29 cells. Thymidylate synthase (TS) catalytic activity in control cells was 2-fold higher in HCT 116 cells compared to HT 29 cells (47 vs. 23 pmol/min/mg). Total TS content increased 1.5- to 3-fold over control in both cell lines during FUra exposure, and ternary complex formation was evident for up to 96 h-dTTP pools were not depleted in FUra-treated cells, suggesting that residual TS catalytic activity was sufficient to maintain dTTP pools relative to demand. Surprisingly, the partial inhibition of TS was accompanied by a striking accumulation of immunoreactive "dUMP" pools in both lines; dUTP pools also increased 2-to 3-fold. In summary, the gradual and stable accumulation of FUra in RNA noted in both lines may account for the thymidine-insensitive component of FUra toxicity. Because dTTP pools were not appreciably diminished, the interference with nascent DNA chain elongation and induction of single-strand breaks in newly synthesized DNA in both cell lines may be due to misincorporation of deoxyuridine nucleotides.

As an alternative to the standard excimer laser used for PRK, we investigated the ablation rate at 213 nm of PMMA, and human corneas under controlled hydration.The output of a frequency-quintupled Nd:YAG laser (213 nm) was transformed into a quasi-Gaussian beam. PMMA and corneal lenticules maintained under controlled hydration were ablated until perforation was detected.The ablation rate of PMMA and cornea at 213 nm were similar to that at 193 nm when radiant exposure was below 200 mJ/cm2 and increased gradually between one and two times faster than that at 193 nm when radiant exposure was200 mJ/ cm2.PMMA and cornea ablation at 213 nm are similar to that at 193 nm and are different from that at 248 nm. The difference between PMMA and cornea ablation rates should be considered when using PMMA to test ablated diopter and smoothness for photorefractive surgery.

This letter presents a bionic study on Parnassius butterfly wings with a prominent ultraviolet (UV)-selective antireflection effect. An accurate SiO2 inverse replica of the nanostructure with a unique optical function from butterfly wings is prepared in multiscale by combining a sol-gel process and subsequent selective etching. It is found that the original nanostructures of biotemplate are well inherited and the excellent UV-antireflection function could be modulated by tunable parameters such as the replica spacing, width, distribution, and shape as well as formation.

When Rhodiola sachalinensis polysaccharides A and B (RSP A and RSP B) were intraperitoneally injected to mice at dosages of 50 mg/kg and 100 mg/kg, the result showed that RSP B was the effective hypoglycemic ingredient of Rhodiola sachalinensis. When mice were administrated in different ways, it was shown that RSP B did not possess significant hypoglycemic effect through absorption in the instestines. However, RSP B does possess significant hypoglycemic effect if administrated subcutaneously, intramuscularly, intraperitoneally and intravenously.